Αλέξανδρος Γ. Σφακιανάκης: Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com, Telephone consultation 11855 int 1193,

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Liver alterations in anorexia nervosa are not caused by insulin resistance AbstractBackground Liver dysfunction has been widely reported in connection with anorexia nervosa (AN) but the pathogenesis of these alterations has never been fully understood despite reported theories about the presence of insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD). The aim of this study is to investigate if hypertransaminasemia in AN is linked to IR and NAFLD.Methods Anthropometric data and laboratory exams of 34 patients and 34 controls were analyzed, including alanine-aminotransferase, aspartate-aminotransferase and homeostatic model assessment of insulin resistance (HOMA-IR) index. All subjects also underwent magnetic resonance imaging (MRI), ultrasonography (US), and transient elastography (TE).Results Evidence of increased alanine aminotransferase in AN patients was confirmed in our sample together with a lower HOMA-IR index compared to controls. Positive results in US appeared in 16 patients vs none in controls (p = 0.0007); patients with liver parenchyma abnormalities in US were not different than normal-US patients in any of the studied variables. Only one patient showed non-alcoholic fatty liver disease in MRI while abnormal TE was found in four patients and never in controls.Conclusions Liver damage suggested by increased serum liver enzymes cannot be due to liver steatosis but potentially to a different liver disease (not identified by MRI) or to an early liver fibrosis not associated with an insulin-resistant status. Association between long boarding time in the emergency department and hospital mortality: a single-center propensity score-based analysis Abstract Once diagnostic work-up and first therapy are completed in patients visiting the emergency department (ED), boarding them within the ED until an in-hospital bed became available is a common practice in busy hospitals. Whether this practice may harm the patients remains a debate. We sought to determine whether an ED boarding time longer than 4 h places the patients at increased risk of in-hospital death. This retrospective, propensity score-matched analysis and propensity score-based inverse probability weighting analysis was conducted in an adult ED in a single, academic, 1136-bed hospital in France. All patients hospitalized via the adult ED from January 1, 2013 to March 31, 2018 were included. Hospital mortality (primary outcome) and hospital length of stay (LOS) were assessed in (1) a matched cohort (1:1 matching of ED visits with or without ED boarding time longer than 4 h but similar propensity score to experience an ED boarding time longer than 4 h); and (2) the whole study cohort. Sensitivity analysis to unmeasured confounding and analyses in pre-specified cohorts of patients were conducted. Among 68,632 included ED visits, 17,271 (25.2%) had an ED boarding time longer than 4 h. Conditional logistic regression performed on a 10,581 pair-matched cohort, and generalized estimating equations with adjustment on confounders and stabilized propensity score-based inverse probability weighting applied on the whole cohort showed a significantly increased risk of hospital death in patients experiencing an ED boarding time longer than 4 h: odds ratio (OR) of 1.13 (95% confidence interval [95% CI] 1.05–1.22), P = 0.001; and OR of 1.12 (95% CI 1.03–1.22), P = 0.007, respectively. Sensitivity analyses showed that these findings might be robust to unmeasured confounding. Hospital LOS was significantly longer in patients exposed to ED boarding time longer than 4 h: median difference 2 days (95% CI 1–2) (P < 0.001) in matched analysis and mean difference 1.15 days (95% CI 1.02–1.28) (P < 0.001) in multivariable unmatched analysis. In this single-center propensity score-based cohort analysis, patients experiencing an ED boarding time longer than 4 h before being transferred to an in-patient bed were at increased risk of hospital death. Risk stratification of patients with chest pain or anginal equivalents in the emergency department Abstract We studied whether previously developed cardiac risk scores—including history, ECG, age, risk factors, and troponin (HEART); Thrombolysis in Myocardial Infarction (TIMI); Global Registry of Acute Coronary Events (GRACE); and Emergency Department Assessment of Chest Pain (EDACS)—could be applied to predict major adverse cardiac events (MACE) in patients with possible coronary artery disease, including anginal equivalents. Patients with chest pain or anginal equivalents who underwent coronary computed tomographic angiography were included. The primary outcome was 30-day MACE. We compared the cardiac risk scores by the area under the receiver-operating characteristic curves (AUC). The primary outcome occurred in 200 patients (16.0%) of the 1247 patients included. For the prediction of MACE, the AUC of the HEART score (0.765) was superior to those of the TIMI (0.726), GRACE (0.612), and EDACS (0.631) scores. Among patients identified by each score as being at low risk, the MACE rate was the lowest for the HEART score (5.7%), followed by the TIMI (8.8%), EDACS (11.2%), and GRACE (12.2%) scores. At a sensitivity level of a < 2% rate of misses, the negative predictive value of the HEART score (1.0) outperformed those of the GRACE (0.932) and EDACS (0.964). The HEART score appeared to be more predictive of MACEs than the TIMI, GRACE, and EDACS in patients with chest pain or anginal equivalents. However, previously suggested cutoff could not safely identify low-risk patients for early discharge because of the unacceptably high rate of missed MACEs. A double-edged sword: e-cigarettes, and other electronic nicotine delivery systems (ENDS): reply Is delayed cardioversion the better approach in recent-onset atrial fibrillation? No Abstract Symptomatic atrial fibrillation (AF) is a common cause of emergency department (ED) referrals. In case of hemodynamic stability, the choice to either perform early cardioversion (pharmacologic or electrical) or to prescribe rate-lowering drugs and differ any attempts to restore sinus rhythm (i.e., wait-and-see approach) has been widely debated. Results of the recent Rate Control versus Electrical Cardioversion Trial 7-Acute Cardioversion versus Wait and See (RACE 7 ACWAS) have been considered a strong argument in favor of the wait-and-see approach. In this debate, we discuss several issues that would support early cardioversion, ranging from patients' satisfaction and costs to concerns about safety. Furthermore, the wait-and-see approach may translate into a missed opportunity to encourage widespread use of a "pill-in-the-pocket" home treatment: this underused option could allow rapid solving of many AF episodes, potentially avoiding future ED referrals. Our opinion is that a delayed cardioversion may introduce unneeded complications in the straightforward management of a common clinical problem. Therefore, early cardioversion should continue to be the preferred option because of its proven efficacy, safety and convenience. Correction to: Incidence of hyperkalemia in the emergency department: a 10-year retrospective study In the original publication of the article, the 3rd author name was swapped. The correct author name should read as Damien Masson. Treatment with ferric carboxymaltose in stable patients with severe iron deficiency anemia in the emergency department Abstract The AABB Choosing Wisely Campaign recommends "don't transfuse for iron deficiency without hemodynamic instability". However, the management of iron deficiency anemia (IDA) in the emergency department (ED) is heterogeneous and patients are often over-transfused. Intravenous iron is effective in correcting anemia and new formulations, including ferric carboxymaltose (FCM), allow the administration of high doses with low immunogenicity. The aim of this retrospective study was to analyze the management of hemodynamically stable patients aged 18–55 years with severe IDA (hemoglobin < 8 g/dL), who presented to the ED from January 2014 to July 2018. Patients who received FCM (FCM1) and those who did not receive FCM (FCM0) were compared. Efficacy and safety of FCM at follow-up were evaluated. Seventy-one subjects fulfilled the inclusion criteria (FCM0 n = 48; FCM1 n = 23). The mean Hb at admission was 6.6 g/dL. 40% in the FCM0 and 13% in FCM1 were transfused (p = 0.02). 21% of FCM0 patients were admitted to the ward, while all FCM1 were discharged (p = 0.02). Within 2 weeks, the Hb increase was 2.8 ± 1 g/dL in the FCM1 group. Sixteen FCM1 patients were evaluated at 52 ± 28 days (median 42, range 27–122): the average Hb increase was 5.3 ± 1.4 g/dL. In summary, we showed that FCM administration in the ED in hemodynamically stable patients was associated with fewer transfusions and hospital admissions compared to the FCM0 group; moreover, it succeeded in safely, effectively and rapidly increasing Hb levels after discharge from the ED. Further studies are needed to develop recommendations for IDA in the ED and to identify transfusion thresholds for non-hospitalized patients. A double-edged sword: E-cigarettes, and other electronic nicotine delivery systems (ENDS) Presence of air in the inferior vena cava: an uncommon radiologic presentation of emphysematous pyelonephritis Two different techniques of ultrasound-guided peripheral venous catheter placement versus the traditional approach in the pre-hospital emergency setting: a randomized study Abstract We performed a randomized pre-hospital clinical study to compare two different techniques of ultrasound-guided peripheral venous catheter (PVC) insertion and the conventional cannulation technique in the pre-hospital emergency setting, with a specific focus on the procedural success rate and the time required to introduce PVC. This pre-hospital prospective controlled randomized clinical trial allocated patients treated by emergency medical service to undergo PVC insertion fully controlled by ultrasound (ultrasound guidance of the PVC tip until it penetrates the lumen, group A), PVC insertion partially controlled by ultrasound (target vein identification only, group B) or to receive PVC without any ultrasound guidance (group C). The study outcomes were monitored until the patient was admitted to the hospital. A total of 300 adult patients were enrolled. The success of the first attempt (group A: 88%, group B: 94%, group C: 76%, p < 0.001) and overall success rate (A: 99%, B: 99%, C: 90%, p < 0.001) were significantly higher in the group A, followed by group B when compared to group C. The number of attempts was significantly lower (A: 1.18 ± 0.54, B: 1.05 ± 0.22, C: 1.22 ± 0.57, p < 0.001) and the time required for the procedure shorter (A: 75.3 ± 60.6, B: 43.5 ± 26.0, C: 82.3 ± 100.9 s, p < 0.001) in group B compared to groups A and C. Both techniques of ultrasound-guided PVC placement were associated with higher success rates than the conventional method. However, PVC insertion partially controlled by ultrasound was superior to full ultrasound guidance in terms of time and number of cannulation attempts required.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Achieving the Lowest Effective Antipsychotic Dose for Patients with Remitted Psychosis: A Proposed Guided Dose-Reduction Algorithm Abstract Continuing antipsychotic treatment in patients with schizophrenia under clinical remission remains controversial. Even though the mainstream opinion declares an outweighed balance against medication discontinuation, recent reviews and critiques suggest that some patients may remain symptom free and well functioning after stopping antipsychotics, but few predictors can identify who can try medication discontinuation, whilst no guidelines exist for reducing medication to reach the lowest effective dose safely. Analyzing the findings from studies employing different methodologies, adopting evidence from pharmacodynamic research, and observing dose reduction in stable patients, as well as taking inspiration from the metaphor of the Cantor set in natural philosophy, we introduce an alternative solution and propose a guided dose-reduction algorithm that follows a set of clear precautions and instructions. The algorithm recommends only a fraction (no more than 25%) of the dosage to be reduced at a time, with at least a 6-month stabilization period required before reducing another 25% of the dose. Patients are empowered to actively participate in decision making when they are ready for further dose tapering, or should they retreat to a previous dosage if warning signs of a relapse re-emerge. An intermittent or irregular dosing schedule can be used to adapt this algorithm to real-world practice. Our preliminary findings suggest that patients with remitted psychosis can do well along this path. We anticipate that this approach can help optimize the risk–benefit ratio and instill a hope in patients with schizophrenia that they can maintain in stable remission under a lower antipsychotic dose without an increased risk of relapse. Acknowledgement to Referees Adverse Events Associated with Melatonin for the Treatment of Primary or Secondary Sleep Disorders: A Systematic Review AbstractBackground Melatonin is widely available either on prescription for the treatment of sleep disorders or as an over-the-counter dietary supplement. Melatonin has also recently been licensed in the UK for the short-term treatment of jetlag. Little is known about the potential for adverse events (AEs), in particular AEs resulting from long-term use. Concern has been raised over the possible risks of exposure in certain populations including pre-adolescent children and patients with epilepsy or asthma.Objectives The aim of this systematic review was to assess the evidence for AEs associated with short-term and longer-term melatonin treatment for sleep disorders.Methods A literature search of the PubMed/Medline database and Google Scholar was conducted to identify randomised, placebo-controlled trials (RCTs) of exogenous melatonin administered for primary or secondary sleep disorders. Studies were included if they reported on both the types and frequencies of AEs. Studies of pre-term infants, studies of < 1 week in duration or involving single doses of melatonin and studies in languages other than English were excluded. Findings from open-label studies that raised concerns relating to AE reports in patients were also examined. Studies were assessed for quality of reporting against the Consolidated Standards of Reporting Trials (CONSORT) checklist and for risk of bias against the Cochrane Collaboration risk-of-bias criteria.Results 37 RCTs met criteria for inclusion. Daily melatonin doses ranged from 0.15 mg to 12 mg. Subjects were monitored for up to 29 weeks, but most studies were of much shorter duration (4 weeks or less). The most frequently reported AEs were daytime sleepiness (1.66%), headache (0.74%), other sleep-related AEs (0.74%), dizziness (0.74%) and hypothermia (0.62%). Very few AEs considered to be serious or of clinical significance were reported. These included agitation, fatigue, mood swings, nightmares, skin irritation and palpitations. Most AEs either resolved spontaneously within a few days with no adjustment in melatonin, or immediately upon withdrawal of treatment. Melatonin was generally regarded as safe and well tolerated. Many studies predated publication of the CONSORT checklist and consequently did not conform closely to the guidelines. Similarly, only eight studies were judged 'good' overall with respect to the Cochrane risk-of-bias criteria. Of the remaining papers, 16 were considered 'fair' and 13 'poor' but publication of almost half of the papers preceded that of the earliest version of the guidelines.Conclusion Few, generally mild to moderate, AEs were associated with exogenous melatonin. No AEs that were life threatening or of major clinical significance were identified. The scarcity of evidence from long-term RCTs, however, limits the conclusions regarding the safety of continuous melatonin therapy over extended periods. There are insufficient robust data to allow a meaningful appraisal of concerns that melatonin may result in more clinically significant adverse effects in potentially at-risk populations. Future studies should be designed to comply with appropriate quality standards for RCTs, which most past studies have not. Fingolimod Increases Brain-Derived Neurotrophic Factor Level Secretion from Circulating T Cells of Patients with Multiple Sclerosis AbstractBackground The pathophysiology of multiple sclerosis involves an autoimmune and a neurodegenerative mechanism. Central nervous system-infiltrating immune cells in multiple sclerosis also possess a neuroprotective activity through secretion of neurotrophins, such as brain-derived neurotrophic factor. Fingolimod was shown to slow the progression of disability and loss of brain volume.Objective The objective of this study was to explore whether fingolimod induces secretion of neurotrophins by immune cells.Methods Blood was drawn from 21 patients before the initiation of treatment with fingolimod and at 6 and 12 months of follow-up. The levels of the neurotrophic factors brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, β-nerve growth factor, neurotrophin-3, neurotrophin-4, basic fibroblast growth factor, epidermal growth factor, and vascular endothelial growth factor were screened in the supernatants of separated T cells and monocyte cultures using a customized, multiplex enzyme-linked immunosorbent assay. Brain-derived neurotrophic factor levels were further validated by a specific enzyme-linked immunosorbent assay.Results Treatment with fingolimod significantly increased brain-derived neurotrophic factor secretion from T cells. A specific enzyme-linked immunosorbent assay confirmed these results in the supernatant of T cells after 6 and 12 months of therapy.Conclusions T cells that reach the bloodstream of fingolimod-treated patients with multiple sclerosis may contribute to the neuroprotective effect of this therapy by increased secretion of brain-derived neurotrophic factor. This mechanism of action of fingolimod in patients with multiple sclerosis has not been previously reported. An Update on Vitamin D and Disease Activity in Multiple Sclerosis Abstract Vitamin D and its main active metabolite 1,25-dihydroxyvitamin D serve a crucial role in maintenance of a healthy calcium metabolism, yet have additional roles in immune and central nervous system cell homeostasis. Serum levels of 25-hydroxyvitamin D are a biomarker of future disease activity in patients with early relapsing–remitting multiple sclerosis (RRMS), and vitamin D supplementation in patients with low circulating 25-dihydroxyvitamin D levels has been anticipated as a potential efficacious treatment strategy. The results of the first large randomized clinical trials (RCTs), the SOLAR and CHOLINE studies, have now been published. The SOLAR study compared 14,000 IU of vitamin D3 (cholecalciferol) per day with placebo for 48 weeks in 232 randomized patients, whereas CHOLINE compared vitamin D3 100,000 IU every other week with placebo for 96 weeks in 129 randomized patients. All patients in both studies also used interferon-β-1a. None of the studies met their primary endpoints, which were no evidence of disease activity (NEDA-3) at 48 weeks in SOLAR and annualized relapse rate at 96 weeks in CHOLINE. Both studies did, however, suggest modest effects on secondary endpoints. Thus, vitamin D reduced the number of new or enlarging lesions and new T2 lesions in SOLAR, and the annualized relapse rate and number of new T1 lesions, volume of hypointense T1 lesions, and disability progression in the 90 patients who completed 96 weeks' follow-up in CHOLINE. We conclude that none of the RCTs on vitamin supplementation in MS have met their primary clinical endpoint in the intention to treat cohorts. This contrasts the observation studies, where each 25 nmol/l increase in 25-hydroxyvitamin D levels were associated with 14–34% reduced relapse risk and 15–50% reduced risk of new lesions on magnetic resonnance imaging. This discrepancy may have several explanations, including confounding and reverse causality in the observational studies. The power calculations of the RCTs have been based on the observational studies, and the RCTs may have been underpowered to detect less prominent yet important effects of vitamin D supplementation. Although the effect of vitamin D supplementation is uncertain and less pronounced than suggested by observational studies, current evidence still support that people with MS should avoid vitamin D insufficiency, and preferentially aim for vitamin D levels around 100 nmol/L or somewhat higher. Ischemic and Thrombotic Events Associated with Concomitant Xa-inhibiting Direct Oral Anticoagulants and Antiepileptic Drugs: Analysis of the FDA Adverse Event Reporting System (FAERS) AbstractIntroduction Factor Xa-inhibiting direct oral anticoagulants (FXa-DOACs) undergo hepatic metabolism via cytochrome P-450 (CYP450). Concomitant use of rifampicin, an inducer of these enzymes, with FXa-DOACs, has been shown to decrease FXa-DOAC concentrations in healthy subjects. Several common antiepileptic drugs (AEDs) are known to induce CYP450 enzymes as well. However, little is known regarding the impact of this potential interaction on treatment outcomes with FXa-DOACs.Methods We analyzed adverse event cases submitted to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from January 2013 to December 2018. We compared the proportion of cases reporting thromboembolic and ischemic adverse events (TAIAEs) with the concomitant use of FXa-DOACs and enzyme-inducing AEDs to the proportion of cases with FXa-DOACs and other AEDs.Results During this period, 9693 adverse event cases reported concomitant use of FXa-DOACs and AEDs. Almost all reports (> 99%) involved the use of rivaroxaban or apixaban. Compared with other AEDs, enzyme-inducing AEDs were associated with an 86% increase in the odds of reporting TAIAEs [reporting odds ratio (ROR) 1.86, 95% confidence interval (CI) 1.61–2.15; p < 0.0001]. In secondary separate analyses of rivaroxaban and apixaban, enzyme-inducing AEDs were similarly associated with increased reporting of a TAIAE (ROR 1.79, 95% CI 1.50–2.12, and ROR 1.88, 95% CI 1.41–2.48, respectively).Conclusion Using real world data, we observed an increase in the odds of reporting anticoagulation treatment failure among patients treated with FXa-DOACs and concomitant enzyme-inducing AEDs compared to those treated with other AEDs. Risk Factors Associated with the Occurrence of Neonatal Opioid Withdrawal Syndrome: A Review Abstract In a number of countries, the prevalence of neonatal opioid withdrawal syndrome (NOWS) is increasing. While NOWS is ultimately the result of opioid exposure in utero, a wide range of risk factors have been associated with the prevalence of NOWS, extending beyond just drug exposure. This article reviews the available literature on factors associated with the incidence of NOWS in opioid-exposed neonates. A range of risk factors have been associated with NOWS, including features of neonatal drug exposure, maternal and neonatal characteristics, aspects of labor and delivery, and genetics. Increased length of gestation and higher birth weight were consistently associated with an increased risk of NOWS, while breast feeding and 'rooming-in' were associated with a reduced risk of NOWS. Additionally, several genetic factors have also been associated with NOWS severity. There is conflicting evidence on the association between NOWS and other risk factors including opioid dose, neonate sex, and the use of some medications during pregnancy. This may be in part attributable to differences in how NOWS is diagnosed and the variety of methodologies across studies. While a large number of risk factors associated with NOWS are non-modifiable, encouraging pregnant women to reduce other drug use (including smoking), breast feed their child, and the judicious use of medications during pregnancy may help reduce the prevalence of NOWS. The presence or absence of NOWS in an opioid-exposed neonate is associated with a wide range of factors. Some of these modifiable risk factors may be potential targets for the primary prevention of NOWS. Recent Advances in Pharmacotherapy for Episodic Migraine Abstract In 2018, three calcitonin gene-related peptide (CGRP) pathway monoclonal antibodies, erenumab, fremanezumab and galcanezumab, were approved in various parts of the world, including Europe and the US, and another, eptinezumab, is pending, for the prevention of migraine. In this article, episodic migraine treatment is reviewed, although these medicines are approved and are just as effective for chronic migraine. These new medicines usher a new phase in the preventive management of migraine with migraine-specific treatments. Data from phase III trials of CGRP pathway monoclonal antibodies have shown they are efficacious, with adverse effect rates comparable to placebo. The combination of clear efficacy and excellent tolerability will be welcome in an area where poor adherence to current preventives is common. Rimegepant, ubrogepant and lasmiditan are migraine-specific acute therapies yet to be approved by regulators. Phase III data for the respective CGRP receptor antagonists, the gepants, and the serotonin 5-HT1F receptor agonist, the ditan, have been positive and free of cardiovascular adverse effects. These medicines are not vasoconstrictors. When approved, they could meet the acute therapy demand of patients with cardiovascular risk factors where triptans are contraindicated. Beyond this, gepants will see the most disruptive development in migraine management in generations with medicines that can have both acute and preventive effects, the latter evidenced by data from the discontinued drug telcagepant and the early-phase drug atogepant. Moreover, one can expect no risk of medication overuse syndromes with gepants since the more patients take, the less migraines they have. During the next years, as experience with monoclonal antibodies grows in clinical practice, we can expect an evolution in migraine management to take shape. Clinicians will be able to offer treatment patients want rather than trying to fit migraineurs into therapeutic boxes for their management. Despite pessimistic susurrations of a largely addlepated form, many patients, and physicians, will welcome new options, and the challenges of new treatment paradigms, with optimism. Targeting Iron Dyshomeostasis for Treatment of Neurodegenerative Disorders Abstract While iron has an important role in the normal functioning of the brain owing to its involvement in several physiological processes, dyshomeostasis has been found in many neurodegenerative disorders, as evidenced by both histopathological and imaging studies. Although the exact causes have remained elusive, the fact that altered iron levels have been found in disparate diseases suggests that iron may contribute to their development and/or progression. As such, the processes involved in iron dyshomeostasis may represent novel therapeutic targets. There are, however, many questions about the exact interplay between neurodegeneration and altered iron homeostasis. Some insight can be gained by considering the parallels with respect to what occurs in healthy aging, which is also characterized by increased iron throughout many regions in the brain along with progressive neurodegeneration. Nevertheless, the exact mechanisms of iron-mediated damage are likely disease specific to a certain degree, given that iron plays a crucial role in many disparate biological processes, which are not always affected in the same way across different neurodegenerative disorders. Moreover, it is not even entirely clear yet whether iron actually has a causative role in all of the diseases where altered iron levels have been noted. For example, there is strong evidence of iron dyshomeostasis leading to neurodegeneration in Parkinson's disease, but there is still some question as to whether changes in iron levels are merely an epiphenomenon in multiple sclerosis. Recent advances in neuroimaging now offer the possibility to detect and monitor iron levels in vivo, which allows for an improved understanding of both the temporal and spatial dynamics of iron changes and associated neurodegeneration compared to post-mortem studies. In this regard, iron-based imaging will likely play an important role in the development of therapeutic approaches aimed at addressing altered iron dynamics in neurodegenerative diseases. Currently, the bulk of such therapies have focused on chelating excess iron. Although there is some evidence that these treatment options may yield some benefit, they are not without their own limitations. They are generally effective at reducing brain iron levels, as assessed by imaging, but clinical benefits are more modest. New drugs that specifically target iron-related pathological processes may offer the possibility to prevent, or at the least, slow down irreversible neurodegeneration, which represents an unmet therapeutic target. The Potential Therapeutic Capacity of Inhibiting the Brain Renin–Angiotensin System in the Treatment of Co-Morbid Conditions in Epilepsy Abstract Epilepsy is one of the most prevalent neurological diseases and although numerous novel anticonvulsants have been approved, the proportion of patients who are refractory to medical treatment of seizures and have progressive co-morbidities such as cognitive impairment and depression remains at about 20–30%. In the last decade, extensive research has identified a therapeutic capacity of the components of the brain renin–angiotensin system (RAS) in seizure- and epilepsy-related phenomena. Alleviating the activity of RAS in the central nervous system is considered to be a potential adjuvant strategy for the treatment of numerous detrimental consequences of epileptogenesis. One of the main advantages of RAS is associated with its modulatory influence on different neurotransmitter systems, thereby exerting a fine-tuning control mechanism for brain excitability. The most recent scientific findings regarding the involvement of the components of brain RAS show that angiotensin II (Ang II), angiotensin-converting enzyme (ACE), Ang II type 1 (AT1) and type 2 (AT2) receptors are involved in the control of epilepsy and its accompanying complications, and therefore they are currently of therapeutic interest in the treatment of this disease. However, data on the role of different components of brain RAS on co-morbid conditions in epilepsy, including hypertension, are insufficient. Experimental and clinical findings related to the involvement of Ang II, ACE, AT1, and AT2 receptors in the control of epilepsy and accompanying complications may point to new therapeutic opportunities and adjuvants for the treatment of common co-morbid conditions of epilepsy.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Predictors and prevalence of bipolar disorders in patients with a major depressive disorder Reda M Ismail, Hala T Mohamed, Rania A Hamed, Sherif A Helal Egyptian Journal of Psychiatry 2019 40(3):127-136 Introduction Onset of bipolar disorder (BD) involves a major depressive episode (MDE) in approximately half of type-I (BD-I) patients and three-quarters of those diagnosed with type-II (BD-II). Aim To detect the soft signs and the predictors of BD in patients with a MDE. Participants and methods A sample of 500 patients was solicited fulfilling the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnostic criteria for a current MDE. Patients were given the HCL-32-R2 questionnaire to assess the presence of manic/hypomanic symptoms; those scoring less than 14 were considered bipolar. We also examined whether demographics, psychiatric history, clinical characteristics, and the incidence of comorbid conditions differed significantly between patients with BD and unipolar disorder. Results A number of factors were highly predictive of bipolarity, including age at illness onset, family history of bipolarity, seasonality, mixed state, manic switch, mood irritability, and mood reactivity. Of the comorbidities examined, thyroid disorders, cardiovascular disorders, generalized anxiety disorder, presence of psychotic features, and borderline personality disorder occurred at a higher rate in patients with BDs than in those with unipolar disorders. Conclusion A number of factors in the patient's psychiatric history as well as clinical aspects of the episode itself may signal an increased likelihood of bipolarity. Schizophrenia symptom dimensions in correlation to patients' demographic and clinical characteristics Samah Rabei, Haitham Osama ElBoraie, Nesrin Elsaadouni, Mohamed Ezzat Elhadidy Egyptian Journal of Psychiatry 2019 40(3):137-140 Background Schizophrenia symptom dimensions could vary with clinical and demographic variables. Materials and methods A total of 100 patients with schizophrenia were diagnosed based on the Diagnostic and statistical manual criteria of the American Psychiatric association. Positive and negative symptom scale was used to assess schizophrenia symptoms. The search for possible correlations between dimensions and demographic and clinical variables was done by Pearson correlation coefficient. Results and conclusion Symptom dimensions showed a correlation with age, onset, duration, hospitalization, compliance to medication, duration without treatment, and family history of schizophrenia. Intercorrelation of symptom dimensions in patients with schizophrenia Nesrin Elsaadouni, Haitham Elboraie, Samah Rabei, Ahmed Elboraie Egyptian Journal of Psychiatry 2019 40(3):141-146 Background The heterogeneity of schizophrenia symptoms is well documented. The positive and negative distinction is limited to cover the entire spectrum of schizophrenia phenomenology. Aim The aim of the study is to find out the major symptom dimensions of phenomenology in a sample of schizophrenic patients. Materials and methods We recruited 100 schizophrenic patients. Diagnosis was based on diagnostic and statistical manual criteria. Positive and negative symptoms scale was used to assess schizophrenia symptoms. Patients' scores were subjected to factor analysis with varimax rotation. Internal consistency was determined by the use of Cronbach's α. Results Five dimensions (factors) were produced: negative, excitement, positive, depressive, and cognitive dimensions. Internal consistency was quite satisfactory. Psychosocial aspects and personality dimensions among a sample of patients with irritable bowel syndrome Hala M Abd Elaziz, Reda M Ismail, Hala T Mohammed, Shimaa Y Abd Elaziz Egyptian Journal of Psychiatry 2019 40(3):147-154 Background Irritable bowel syndrome (IBS) is a chronic functional disorder of the gastrointestinal tract, a burden to society through total direct costs, reduced social functioning, and quality of life impairment. Aim The aim of the study was to determine the associated psychosocial risk factors and personality traits in a sample of IBS patients. Participants and methods A total of 100 patients of IBS were recruited from the Gastroenterology and Internal Medicine Outpatient Clinics Departments at Al Zahraa University Hospital during the period from January 2018 to August 2018 and 100 apparently healthy participants as the control group (aged 18–45 years) were subjected to clinical psychiatric assessment, Eysenck's Personality Questionnaire, Stressor life events questionnaire, and Structured Clinical Interview for DSM-IV Axis I. Results The total number of cases was 100 [25 (25%) men and 75 (75%) women] with a mean age of 34.18±6.4 years; there was statistical significance regarding age, sex, marital status, and high significance in family history of IBS, education, employment; 51% had long duration of illness of more than 5 years. High neuroticism score was detected in 63% of the patients versus (VS) 20% of the control group and 52% of the patients had low extroversion VS 16% in the control group. There was high statistical significance in family, economic, social, emotional, health, and personal stressors. Moreover, 66% of the patients had psychiatric comorbidity, high statistical significance with generalized anxiety disorder and hypochondriasis, and statistical significance with somatization, dysthymic disorder, mixed anxiety depression, and panic disorder. Conclusion In this study, we found that IBS was associated with significant psychological distress and psychiatric comorbidities as psychosocial factors, so good assessment and early recognition will permit early intervention to improve outcome of the IBS and quality of life. Effect of adult attention-deficit hyperactivity on disability and quality of life of bipolar patients Amira A Fouad, Heba A Fouad, Shimaa I Amin Egyptian Journal of Psychiatry 2019 40(3):155-161 Background Attention-deficit hyperactivity disorder (ADHD) is a common psychiatric disease, usually first diagnosed during childhood or adolescence. A significant portion (∼50–65%) of ADHD symptoms persist into adulthood. Adult ADHD and bipolar disorder (BD) are common comorbid psychiatric conditions. Comorbidity between BD and adult ADHD has been reported in both ADHD and BD cases. Aim To determine the effect of comorbid adult ADHD on disability and quality of life of patients with bipolar disorder. Patients and methods This is a cross-sectional study that was done at the Psychiatric Department in the Zagazig University Hospitals, Sharkia Governorate, Egypt, during the period from May to November, 2017. One hundred and two euthymic patients with Diagnostic and statistical manual of mental disorders, 4th ed. − text revision diagnosis of BD I were selected by simple random probability sampling from the patients with bipolar disorder who came for follow-up and to receive their medications from psychiatric outpatient clinic. Results The mean age of the participants ranged from 18 to 40 years, and 51% were female. Patients with bipolar disorder with adult ADHD had more disability in work, social life, and family life than patients with pure bipolar disorder. Moreover, patients with bipolar disorder without adult ADHD had significant better quality of life in all domains as reflected by higher scores in WHO quality-of-life scale than patients with adult ADHD. Conclusion Adult ADHD is a frequent comorbid disorder in patients with BD. Adult ADHD comorbidity negatively affects functioning and quality of life of patients with BD. Psychiatric aspects of children who witness domestic violence Zeinab Gomma, El Sayed Saleh, Yomna Rizk, Dalia Asfour Egyptian Journal of Psychiatry 2019 40(3):162-169 Background The presence of domestic violence witnessed by children leads to development of different mental disorders of childhood. Objectives This study was aimed to assess the prevalence of psychiatric disorders in children who witness domestic violence. Patients and methods A community-based case–control study was designed to assess the prevalence of psychiatric disorder in children who witness domestic violence of both sexes aged 6–18 years old with different socioeconomic classes. Tools of measurement used in the current study were Hurt, Insulted, Threatened with Harm and Screamed tool; socioeconomic scale by El-Gilany; symptoms check list (SCL-90); and Structured Clinical Interview for DSM-IV Childhood Diagnoses for child's interview. Results The most common disorders among children witness domestic violence is conduct disorder (15%), major depressive disorder (10%), and attention-deficit hyperactive disorder (8.3%). Children who are not affected among studied families (cases) represented 33.3%. There was a statistically significant difference among cases that witness domestic violence and controls who did not witness it regarding additional signs, loss of appetite, insomniac problems, death ideas, aggressive symptom, and reactive sensitivity symptoms reported as well as global stress indices measured by SCL-90. The most common reason for domestic violence was the financial reasons. Fathers are more responsible for most of the violence incidents. Conclusions Ignoring of suffering and the long duration spent with domestic violent atmosphere without seeking help increase the risk for psychiatric disorder in those children. So legal empowerment and aid projects are essential in raising awareness to influence cultural change and put an end to domestic violence.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Multicellular growth of the Basidiomycota phytopathogen fungus Sporisorium reilianum induced by acid conditions Abstract Fungi are considered model organisms for the analysis of important phenomena of eukaryotes. For example, some of them have been described as models to understand the phenomenon of multicellularity acquisition by different unicellular organisms phylogenetically distant. Interestingly, in this work, we describe the multicellular development in the model fungus S. reilianum. We observed that Sporisorium reilianum, a Basidiomycota cereal pathogen that at neutral pH grows with a yeast-like morphology during its saprophytic haploid stage, when incubated at acid pH grew in the form of multicellular clusters. The multicellularity observed in S. reilianum was of clonal type, where buds of "stem" cells growing as yeasts remain joined by their cell wall septa, after cytokinesis. The elaboration and analysis of a regulatory network of S. reilianum showed that the putative zinc finger transcription factor CBQ73544.1 regulates a number of genes involved in cell cycle, cellular division, signal transduction pathways, and biogenesis of cell wall. Interestingly, homologous of these genes have been found to be regulated during Saccharomyces cerevisiae multicellular growth. In adddition, some of these genes were found to be negatively regulated during multicellularity of S. reilianum. With these data, we suggest that S. reilianum is an interesting model for the study of multicellular development. Combination of mass spectrometry and DNA sequencing for detection of antibiotic resistance in diagnostic laboratories Abstract In the last two decades, microbiology laboratories have radically changed by the introduction of novel technologies, like Next-Generation Sequencing (NGS) and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS). Nevertheless, emergence of antibiotic-resistant microorganisms represents a global threat of current medicine, being responsible for increasing mortality and health-care direct and indirect costs. In addition, the identification of antibiotic-resistant microorganisms, like OXA-48 carbapenemase-producing Enterobacteriaceae, has been changeling for clinical microbiology laboratories. Even the cost of NGS technology and MALDI-TOF MS equipment is relatively high, both technologies are increasingly used in diagnostic and research protocols. Therefore, the aim of this review is to present applications of these technologies used in clinical microbiology, especially in detection of antibiotic resistance and its surveillance, and to propose a combinatory approach of MALDI-TOF MS and NGS for the investigation of microbial associated infections. Assessing the intestinal carriage rates of vancomycin-resistant enterococci (VRE) at a tertiary care hospital in Hungary Abstract Excessive use of antibiotics contributes to the selection of resistant bacteria and intestinal colonization with multiresistant pathogens poses a risk factor for subsequent infections. The present study assessed vancomycin-resistant enterococci (VRE) carriage rates in patients admitted to our tertiary care hospital. Stool samples sent for routine culturing were screened with vancomycin containing solid or broth enrichment media. VRE isolates were identified with matrix-assisted laser desorption/ionization-time of flight mass spectrometry and antibiotic susceptibilities were tested by E-test. Vancomycin resistance genes were detected by polymerase chain reaction. Medical records of carriers were examined for suspected risk factors for colonization. Altogether 3025 stool specimens were analyzed. Solid media identified a VRE carriage rate of 2.2% while broth enrichment detected 5.8%. Seventy percent of the isolates were Enterococcus faecium. VanB genotype was detected in 38.2%, VanA in 37.3%, VanC1 in 22.6%, and VanC2 in 1.9%. All VRE were sensitive to linezolid, daptomycin, and tigecycline. Collective risk factors for carriage were diabetes, normal flora absence, Clostridioides difficile positivity, longer hospital stay, and advanced age. 78.5% of the carriers received antibiotic therapy which was metronidazole in most cases (47.3%). We recommend regular screening of risk groups such as patients with diabetes, history of recent hospitalization, or former C. difficile infection as an imperative step for preventing VRE dissemination. Atypical URA5 gene restriction fragment length polymorphism banding profile in Cryptococcus neoformans strains Abstract URA5-RFLP is one of the most widely used genotyping methods relating to Cryptococcus neoformans and C. gattii consensus genotype nomenclature. In order to identify a molecular type, this method uses a visual comparison of digested PCR products of tested and reference strains, therefore any anomaly in RFLP patterns of studied isolates makes recognition difficult or impossible. This report describes a strain of VNIV type showing an atypical URA5-RFLP pattern as well as a group of AD hybrids displaying the same anomaly. The atypical RFLP pattern is the result of a point mutation and emergence of a new restriction site. Emergence of the allele presenting a new banding pattern may lead to misidentification using the URA5-RFLP technique; the results of this study as well as the literature data may suggest the spread of the allele in the environment. Production of pyruvic acid from glycerol by Yarrowia lipolytica Abstract The aim of the study was to screen Yarrowia lipolytica strains for keto acid production and determine optimal conditions for pyruvic acid biosynthesis from glycerol by the best producer. The analyzed parameters were thiamine concentration, medium pH, stirring speed, and substrate concentration. The screening was performed in flask cultures, whereas pyruvic acid production was carried out in 5-L stirred-tank reactor with 2 L of working volume. In total, 24 Y. lipolytica strains were compared for their abilities to produce pyruvic and α-ketoglutaric acids. The total concentration of both acids ranged from 0.1 to 15.03 g/L. Ten strains were selected for keto acid biosynthesis in bioreactor. The Y. lipolytica SKO 6 strain was identified as the best producer of pyruvic acid. In the selected conditions (thiamine concentration 1.5 μg/L, pH 4.0, stirring speed 800 rpm, 150 g/L of glycerol), the strain Y. lipolytica SKO 6 produced 99.3 g/L of pyruvic acid, with process yield of 0.63 g/g and volumetric production rate of 1.18 g/L/h. Higher titer of pyruvic acid was obtained during fed-batch culture with 200 g/L of glycerol, reaching 125.8 g/L from pure glycerol (yield 0.68 g/g) and 124.4 g/L from crude glycerol (yield 0.62 g/g). Results obtained for the strain Y. lipolytica SKO 6 proved the suitability of microbial production of pyruvic acid at industrial scale. Characterization of Salmonella Typhimurium and its monophasic variant 1,4, [5],12:i:- isolated from different sources Abstract In order to characterize the most commonly detected Salmonella serotypes, we tested 124 isolates of S. Typhimurium and 89 isolates of the monophasic variant of S. Typhimurium (S. 1,4, [5],12:i:-) for their antimicrobial susceptibility by means of the Kirby–Bauer disk-diffusion method, and for the detection of 19 genes (four Phage Markers (g13, Sieb, eat, g8), ten prophage-related virulence genes (gipA, gtgB, nanH, gogB, grvA, sopE, sspH1, sspH2, sodC1, gtgE), and five plasmid-borne virulence genes (spvC, pefA, mig5, rcK, srgA)) by means of PCR-based assays. A total of 213 strains were analyzed from, humans (n = 122), animals (n = 25), food (n = 46), and irrigation water (n = 20). S. Typhimurium isolates showed higher variability, in both their resistance profiles and molecular typing, than S. 1,4, [5],12:i:-. Strains from irrigation water displayed significantly higher susceptibility to antibiotics than those from the other sources. Resistance to ampicillin, streptomycin, sulfonamide, and tetracycline was the most commonly detected resistance profile (R-type), being in serovar S. 1,4, [5],12:i:-, frequently associated to resistance to other antimicrobials. Significant differences in genetic profiles in the two abovementioned Salmonella serotypes were found. None of the plasmid-borne virulence genes investigated were detected in S. 1,4, [5],12:i:- isolates, while those genes, characterized 37.9% of the S. Typhimurium strains. Differences in the prevalence of some molecular targets between the two Salmonella serotypes deserve further study. Importantly, the grvA gene was found exclusively in S. Typhimurium strains, whereas sopE, sodC, gtgB, and gipA were mainly detected, with a statistically significant difference, in S. 1,4, [5],12:i:- isolates. Metabolic profiling of Fusarium oxysporum f. sp. conglutinans race 2 in dual cultures with biocontrol agents Bacillus amyloliquefaciens , Pseudomonas aeruginosa , and Trichoderma harzianum Abstract There are increasing efforts to identify biocontrol-active microbial metabolites in order to improve strategies for biocontrol of phytopathogens. In this work, Fusarium oxysporum f. sp. conglutinans was confronted with three different biocontrol agents: Trichoderma harzianum, Bacillus amyloliquefaciens, and Pseudomonas aeruginosa in dual culture bioassays. Metabolites produced during the microbial interactions were screened by a matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). T. harzianum exhibited the strongest inhibition of growth of F. oxysporum resulting in overlay of the pathogen colony with its mycelium. Recorded metabolite profiles suggested a direct attack of F. oxysporum mycelium by T. harzianum and B. amyloliquefaciens by means of membrane-attacking peptaibols and a set of antimicrobial lipopeptides and siderophores, respectively. The direct mode of the biocontrol activity of T. harzianum and B. amyloliquefaciens corresponded to their ability to suppress F. oxysporum production of mycotoxin beauvericin suggesting that this ability is not specific only for Trichoderma species. In the case of P. aeruginosa, siderophores pyoverdine E/D and two rhamnolipids were produced as major bacterial metabolites; the rhamnolipid production was blocked by F. oxysporum. The results showed that this type of biocontrol activity was the least effective against F. oxysporum. The effective application of MALDI-MS profiling to the screening of nonvolatile microbial metabolites produced during the interaction of the phytopathogen and the biocontrol microorganisms was demonstrated. The acid phosphatase Pho5 of Saccharomyces cerevisiae is not involved in polyphosphate breakdown Abstract Inorganic polyphosphate is involved in architecture and functioning of yeast cell wall. The strain of Saccharomyces cerevisiae constitutively overexpressing acid phosphatase Pho5 was constructed for studying the Pho5 properties and its possible participation in polyphosphate metabolism. The parent strain was transformed by the vector carrying the PHO5 gene under a strong constitutive promoter of glyceraldehyde-3-phosphate dehydrogenase of S. cerevisiae. The culture liquid and biomass of transformant strain contained approximately equal total acid phosphatase activity. The levels of acid phosphatase activity associated with the cell wall and culture liquid increased in the transformant strain compared to the parent strain ~ 10- and 20-fold, respectively. The Pho5 preparation (specific activity of 46 U/mg protein and yield of 95 U/L) was obtained from culture liquid of overproducing strain. The overproducing strain had no changes in polyphosphate level. The activity of Pho5 with long-chained polyP was negligible. We concluded that Pho5 is not involved in polyphosphate metabolism. Purified Pho5 showed a similar activity with p-nitrophenylphosphate, ATP, ADP, glycerophosphate, and glucose-6-phosphate. The substrate specificity of Pho5 and its extracellular localization suggest its function: the hydrolysis of organic compounds with phosphoester bonds at phosphate limitation. The influence of N and S poles of static magnetic field (SMF) on Candida albicans hyphal formation and antifungal activity of amphotericin B Abstract Due to the increasing number of Candida albicans' infections and the resistance of this pathogenic fungus to drugs, new therapeutic strategies are sought. One of such strategies may be the use of static magnetic field (SMF). C. albicans cultures were subjected to static magnetic field of the induction 0.5 T in the presence of fluconazole and amphotericin B. We identified a reduction of C. albicans hyphal length. Also, a statistically significant additional effect on the viability of C. albicans was revealed when SMF was combined with the antimycotic drug amphotericin B. The synergistic effect of this antimycotic and SMF may be due to the fact that amphotericin B binds to ergosterol in plasma membrane and SMF similarly to MF could influence domain orientation in plasma membrane (PM). Community structures and comparison of nosZ and 16S rRNA genes from culturable denitrifying bacteria Abstract The objectives of this study were (i) to isolate and characterize of cultivable denitrifying bacteria using classic microbiological and molecular methods, (ii) to compare of 16S rRNA and nosZ genes as molecular markers, (iii) to determine bacterial community structure and diversity in soil samples using single-strand conformation polymorphism (SSCP) analysis. In this study, 49 bacterial isolates were cultivated and phylogenetic analyses grouped them into two phyla: Proteobacteria (37 species) and Firmicutes (12 species). Our study showed that the nosZ functional gen could be used to identify denitrifying bacteria abundance in environment but could not be used to identify pure bacterial cultures. In addition, the bacterial community structure showed significant differences among the various soil types. Phylogenetic analysis of community structure indicated that 51 clones could be divided into 2 phylotypes. Uncultured bacteria (80.4%) and Gammaproteobacteria (19.6%) were the dominant components of the soil bacterial community. For 16S rRNA, PCR products of 49 bacteria were obtained with 27F-1492R primer pairs. For nosZ, PCR products were obtained with primers 1F-1R (259 bp), 2F-2R (267 bp), and F-1622R (453 bp) of 39 bacteria that the single nosZ band provided on the agarose gel. The bacterial 16S rRNA gene clone library was dominated by Gammaproteobacteria and Bacilli. The nosZ clone sequences did not represent the bacteria from which they were obtained but were found to be closer to the environmental clones. Our study showed that the nosZ functional gene could be used to identify denitrification abundance in environment but could not be used to identify pure bacterial cultures. It was also found that the nosZ sequences showed uncultured denitrifier species.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Spatiotemporal clustering of suicides in the US from 1999 to 2016: a spatial epidemiological approach AbstractPurpose This study aims to describe and characterize the spatial and temporal clustering patterns of suicide in the ten states with the greatest suicide burden in the United States from 1999 to 2016.Methods All suicide deaths from January 1, 1999 to December 31, 2016 in the United States were identified using data from the Wide-ranging Online Data for Epidemiologic Research (WONDER) dataset. The ten states with the highest age-adjusted suicide rates were Montana, Alaska, Wyoming, New Mexico, Nevada, Utah, Idaho, Colorado, Arizona, and Oklahoma. A spatiotemporal scan statistic using a discrete Poisson model was employed to retrospectively detect spatiotemporal suicide clusters.Results From 1999 to 2016, a total of 649,843 suicides were recorded in the United States. Nineteen statistically significant spatiotemporal suicide mortality clusters were identified in the states with the greatest suicide rates, and 13.53% of the suicide cases within these states clustered spatiotemporally. The risk ratio of the clusters ranged from 1.45 to 3.64 (p < 0.001). All states had at least one cluster, with three clusters spanning multiple states, and four clusters were found in Arizona. While there was no clear secular trend in the average size of suicide clusters, the number of clusters increased from 1999 to 2016.Conclusions Hot spots for suicidal behavior in the United States warrant public health intervention and continued surveillance. As suicide rates in the US continue to increase annually, public health efforts could be maximized by focusing on regions with substantial clustering. Predictive factors for changes in quality of life among children and adolescents in youth welfare institutions AbstractPurpose Children and adolescents living in youth welfare institutions often have a below average quality of life (QoL), for reasons that include developmental difficulties, history of traumatic experiences, and mental disorders. Youth welfare measures are needed that would have a positive impact, but there is a lack of longitudinal research on which measures are most effective. This study investigated what factors are associated with an improvement in QoL during residential stay.Methods Residents of youth care facilities in Switzerland and their professional caregivers completed questionnaires that addressed QoL, psychopathology, and experience of traumatic events at two time points. In addition, information regarding mental disorders was obtained through structured clinical interviews. Analyses were conducted on the data obtained from 204 respondents aged 11–18 years. Comparisons with a school sample were conducted.Results Compared to a school sample, a majority of participants rated their QoL equal, whereas their caregivers rated it as lower. Factors predictive of a poorer QoL were high levels of internalizing and externalizing psychopathology, presence of co-morbidities, and female gender. At the second assessment, the caregivers reported a small improvement, which was associated with reductions in both internalizing and externalizing psychopathology.Conclusions The finding that a reduction in severity of psychopathology may result in an improvement in QoL underlines the importance of providing professional support for mentally ill residents of youth welfare institutions. Further research is needed to determine the causality of this association. Depressive symptoms, suicidal ideation, and mental health care-seeking in central Mozambique AbstractPurpose There is scant research on depressive symptoms (DS), suicidal ideation (SI), and mental health care-seeking in Mozambique.Methods Generalized estimating equations were used to assess factors associated with DS, SI, and mental health care-seeking among 3080 individuals interviewed in a representative household survey in Sofala and Manica provinces, Mozambique.Results 19% (CI 17–21%) of respondents reported DS in the past year and 17% (CI 15–18%) lifetime SI. Overall, only 10% (CI 8–11%) of respondents ever sought any care for mental illness, though 26% (CI 23–29%) of those reporting DS and/or SI sought care. 90% of those who sought care for DS received treatment; however, only 46% of those who sought care for SI received treatment. Factors associated with DS and SI include: female gender, divorced/separated, widowed, and > 55 years old. Respondents in the bottom wealth quintile reported lower DS, while those in upper wealth quintiles reported higher prevalence of SI. Individuals with DS or SI had significantly elevated measures of disability—especially in doing household chores, work/school activities, standing for long periods, and walking long distances. Factors associated with care-seeking include: female gender, rural residence, divorced/separated, and > 45 years old. Individuals in lower wealth quintiles and with no religious affiliation had lower odds of seeking care.Conclusions DS and SI are prevalent in central Mozambique and treatment gaps are high (68% and 89%, respectively). An urgent need exists for demand- and supply-side interventions to optimize the delivery of comprehensive community-based mental healthcare in Mozambique. Factors associated with discontinuation of antidepressant treatment after a single prescription among patients aged 55 or over: evidence from English primary care AbstractPurpose Antidepressants are frequently prescribed to older people with depression but little is known on predictors of discontinuation in this population. We, therefore, investigated factors associated with early discontinuation of antidepressants in older adults with new diagnoses or symptoms of depression in English primary care.Methods Data from a nationally representative cohort of patients aged 55 and over were used to evaluate the association between discontinuation of antidepressant medication after a single prescription and potential explanatory variables, including socio-demographic factors, polypharmacy and age-related problems such as dementia.Results Overall, during the study period we observed 34,715 new courses of antidepressant treatment initiated after recorded symptoms or diagnoses of depression. Antidepressant discontinuation after a single prescription was more common in people with depressive symptoms (32%) than in those with diagnosed depression (21.6%). In those diagnosed with depression and in women with depressive symptoms we found that, after adjusting for confounders, the odds of early discontinuation significantly increased after age 65 with a peak at around age 80 and then either levelled or reduced thereafter. Early discontinuation was also significantly less common in people with dementia and in those with diagnosed depression living in more rural areas.Conclusions Early discontinuation of antidepressants increases in the post-retirement years and is higher in those with no formal diagnosis of depression, those without dementia and those with diagnosed depression living in urban areas. Alternative treatment strategies, such as non-drug therapies, or more active patient follow-up should be further considered in these circumstances. Physical activity of people with mental disorders compared to the general population: a systematic review of longitudinal cohort studies AbstractPurpose We investigated if (a) people with lower physical activity have an increased risk of subsequent mental disorders (compared to those with higher physical activity); and (b) people with mental disorders have reduced subsequent physical activity (compared to those without mental disorders).Methods A systematic review of population-based longitudinal studies examining physical activity and mental disorders was conducted. Mental disorders were defined by International Classification of Diseases or Diagnostic and Statistical Manual of Mental Disorders. The results were described in a narrative summary.Results Twenty-two studies were included. The majority (19) examined mood disorders and physical activity. Only two studies found consistent association between lower physical activity and a reduced risk of subsequent mental disorders. One study found the bidirectional association between physical activity and major depression. Twelve studies found mixed results (i.e., no consistency in direction and significance of the findings), and seven studies found no association between the variables of interest.Conclusions There is a lack of consistent evidence linking physical activity to be either a risk factor or consequence of mental disorders.PROSPERO registration ID CRD42017071737. Concurrent use of benzodiazepines, antidepressants, and opioid analgesics with zolpidem and risk for suicide: a case–control and case–crossover study AbstractPurpose To evaluate whether the concurrent use of benzodiazepines, antidepressants, and opioid analgesics with zolpidem increases the risk of suicide or triggers suicide compared with the use of zolpidem alone.Methods We conducted a case–control and case–crossover study using the Korean National Health Insurance Service-National Sample Cohort database. Cases were older than 20 years with a suicide record (International Codes of Disease 10th Revision codes: X-60-X84 and Y87.0 intentional self-harm) between January 1, 2004, and December 31, 2013. For case–control design, ten controls were matched to each case by age, sex, index year, region, income, and health insurance type. For case–crossover analysis, we set hazard period to 60 days and assigned five corresponding sets of control periods of equal length. Exposure was assessed during 60 days before suicide for combinations of benzodiazepines, antidepressants, opioid analgesics with zolpidem against zolpidem alone. We conducted a conditional logistic regression to estimate odds ratios (ORs) and their 95% confidence intervals (CIs).Results In the case–control study, the risk of suicide was 2.80-fold higher in cases taking benzodiazepines and antidepressants with zolpidem than in those taking zolpidem alone (adjusted OR [aOR], 2.80; 95% CI, 1.38–5.70). However, in the case–crossover study, suicide risk showed no significant difference (crude OR [cOR], 0.92; 95% CI, 0.55–1.52) and was underpowered.Conclusions The results of the traditional case–control study confirmed that the concurrent use of benzodiazepines and antidepressants with zolpidem was associated with an increased risk of suicide compared with the use of zolpidem alone. However, there was no significant difference in the magnitude of risk in the within-person comparison design. Barriers and predictors of medication use for childhood ADHD: findings from a UK population-representative cohort AbstractPurpose Little is known about sociodemographic and clinical factors that predict and act as barriers to ADHD medication independently of symptom severity. We examined the proportion of children using medication for ADHD, age of initiation of medication, and predictors of medication use in a population-representative cohort.Methods Data from the Millennium Cohort Study on child ADHD, medication use for ADHD at age 14 (in 2014–2015) and child, parent and sociodemographic variables were collated. Logistic regression models were used to identify factors that predict medication use for ADHD (the main outcome measure), adjusting for symptom severity at age seven.Results The weighted prevalence of ADHD was 3.97% (N = 11,708). 45.57% of children with ADHD (N = 305) were taking medication. The median age at initiation was 9 years (range 3–14). Male gender (AOR 3.66, 95% CI 1.75, 7.66) and conduct problems at age seven (AOR 1.24 95% CI 1.04, 1.47) and 14 predicted medication use at age 14 after adjusting for symptom severity.Conclusions Our study is the first to assess predictors of medication whist adjusting for ADHD symptom severity. Girls with ADHD were less likely to be prescribed medication, even when they displayed similar ADHD symptom levels to boys. Conduct problems also predicted medication independently of ADHD symptoms. ADHD may be more often medicated in boys because clinicians may think a prototypical ADHD child is male, and perhaps conduct problems make boys more disruptive in the classroom, leading to boys being more often treated. The role of neuroticism in self-harm and suicidal ideation: results from two UK population-based cohorts AbstractBackground Self-harm is common, debilitating and associated with completed suicide and increased all-cause mortality, but there is uncertainty about its causal risk factors, limiting risk assessment and effective management. Neuroticism is a stable personality trait associated with self-harm and suicidal ideation, and correlated with coping styles, but its value as an independent predictor of these outcomes is disputed.Methods Prior history of hospital-treated self-harm was obtained by record-linkage to administrative health data in Generation Scotland:Scottish Family Health Study (N = 15,798; self-harm cases = 339) and by a self-report variable in UK Biobank (N = 35,227; self-harm cases = 772). Neuroticism in both cohorts was measured using the Eysenck Personality Questionnaire-Short Form. Associations of neuroticism with self-harm were tested using multivariable regression following adjustment for age, sex, cognitive ability, educational attainment, socioeconomic deprivation, and relationship status. A subset of GS:SFHS was followed-up with suicidal ideation elicited by self-report (n = 3342, suicidal ideation cases = 158) and coping styles measured by the Coping Inventory for Stressful Situations. The relationship of neuroticism to suicidal ideation, and the role of coping style, was then investigated using multivariable logistic regression.Results Neuroticism was positively associated with hospital-associated self-harm in GS:SFHS (per EPQ-SF unit odds ratio 1.2 95% credible interval 1.1–1.2, pFDR 0.0003) and UKB (per EPQ-SF unit odds ratio 1.1 95% confidence interval 1.1–1.2, pFDR 9.8 × 10−17). Neuroticism, and the neuroticism-correlated coping style, emotion-oriented coping (EoC), were also associated with suicidal ideation in multivariable models.Conclusions Neuroticism is an independent predictor of hospital-treated self-harm risk. Neuroticism and emotion-orientated coping styles are also predictive of suicidal ideation. Suicide mortality follow-up of the Swiss National Cohort (1990–2014): sex-specific risk estimates by occupational socio-economic group in working-age population AbstractPurpose To identify occupations and socio-economic groups with detrimental or protective effect on suicide mortality.Methods For every occupation and economic activity/industry, we computed directly age-standardized mortality rates (DSRs) using the age structure of the European population (2010) and standardized mortality ratios (SMRs) for suicide using national cause-specific mortality rates. We further stratified analyses by socio-economic variables, job-skill level, and by three calendar periods (1990–1998/1999–2006/2007–2014).Results The study sample comprised 5,834,618 participants (94,918,456 person-years). The highest DSRs were observed among unemployed/job-seeking group, in agricultural, fishery and related male workers, and in health and social activities female workers. The lowest DSRs were observed in real estate and renting, research and development, IT and other business activities in men and in agriculture, hunting and forestry industry in women. A consistent reduction in DSRs across three calendar periods was observed in men. In female corporate managers, DSRs increased over the 2007–2014 period compared with 1999–2006. Compared to general working-age population, unemployed/job-seeking people, manufacturing labourers, personal care and related workers, and motor vehicle drivers of both sexes were identified at risk of suicide. Moreover, an excess of suicide was observed among male material recording and transport clerks; nursing and midwife-associated professionals; and agricultural workers as well as among female writers and performing artists.Conclusions The findings suggest the detrimental effect of low socioeconomic positions, including unemployment, with respect to suicide mortality and a relationship between suicide and poor psychosocial working conditions in elementary occupations. Sex-specific results need further investigation. Identifying typologies among persons admitted to hospital for non-fatal intentional self-harm in Victoria, Australia AbstractPurpose The aim of this study was to determine whether people who have been hospitalised as the result of non-fatal self-harm form meaningful groups based on mechanism of injury, and demographic and mental health-related factors.Methods A retrospective analysis of 18,103 hospital admissions for self-harm in Victoria, Australia over the 3-year period 2014/2015–2016/2017 recorded on the Victorian Admitted Episodes Dataset (VAED). The VAED records all hospital admissions in public and private hospitals in Victoria. The primary analysis used a two-step method of cluster analysis. Initial analysis determined two distinct groups, one composed of individuals who had a recorded mental illness diagnosis and one composed of individuals with no recorded mental illness diagnosis. Subsequent cluster analysis identified four subgroups within each of the initial two groups.Results Within the diagnosed mental illness subgroups, each subgroup was characterised by a particular mental disorder or a combination of disorders. Within the no diagnosis of mental illness groups, the youngest group was also the most homogenous (all females who self-poisoned), the oldest group had a high proportion of rural/regional residents, the group with the highest proportion of males also had the highest proportion of people who used cutting as the method of self-harm, and the group with the highest proportion of metropolitan residents also had the highest proportion of people who were married.Conclusions Preventative interventions need to take into account that those who are admitted to hospital for self-harm are a heterogeneous group.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Thyroidology and public health: Challenges within the medical profession Sanjay Kalra Thyroid Research and Practice 2019 16(3):93-94 Assessment of serum midkine level in benign and malignant thyroid nodules. Can midkine be a marker of thyroid malignancy? Nermin Ahmed Sheriba, Maram Mohamed Mahdy, Rana Hashem Ibrahim Elattary, Maha Mohamed El-Nabarawy Thyroid Research and Practice 2019 16(3):95-99 Background: Thyroid nodules are a common clinical problem. The prevalence of malignancy in thyroid nodules is currently about 5%–15%. Fine-needle aspiration biopsy (FNAB) has improved the preoperative prediction of malignancy, but still has disadvantages including operator variability and nondiagnostic reports. Midkine (MK) is a novel heparin-binding growth factor; MK levels have been proposed as indicative of malignancy in numerous tumors. MK overexpression in thyroid cancer has been reported to be in correlation with clinicopathological features of the tumor, hypothesizing that MK might play a role as a biomarker for diagnosis and more aggressive behavior of thyroid cancer. Aim: The aim of this study is to evaluate the value of serum MK (SMK) as a marker of malignancy in patients with nodular thyroid disease. Patients and Methods: The current study included 75 individuals with age ranging from 25 to 80 years divided into 25 with malignant thyroid nodule (Group A), 25 with benign thyroid nodule (Group B), and 25 healthy individuals as a control group (Group C). Free triiodothyronine, free thyroxin, thyroid-stimulating hormone, and SMK levels were assessed. Individuals with thyroid nodules were submitted for neck ultrasonography and FNAB. Results: On comparing the three studied groups, a high statistically significant difference in plasma MK levels was found (P < 0.001), being higher in Group A (malignant nodule) with a mean of 1.127 ± 0.527 than Group B (benign nodule) with a mean of 0.536 ± 0.301 with P < 0.001* and also higher in Group A (malignant nodule) with a mean of 1.127 ± 0.527 than Group C (control) with a mean of 0.366 ± 0.230 with P < 0.001*. There was significant difference regarding MK levels, with thyroid nodule contour being higher in thyroid nodule with irregular contour than thyroid nodule with regular contour (P < 0.001*) and calcification being higher in microcalcification than macrocalcification (P = 0.006*). There was high statistically significant difference regarding the level of MK between papillary carcinoma and follicular carcinoma (P < 0.001*). Conclusions: SMK might be the indicator of malignant thyroid cytopathology, suggesting that MK might serve as a novel biomarker in the assessment of thyroid nodules. The present study explored the usefulness of MK as a biomarker in the differentiation between benign and malignant thyroid nodules in samples from serum. Morphological variations of the thyroid gland: An insight on embryological and clinicoanatomical considerations Honnegowda Thittamaranahalli Muguregowda, G Krishna, KG Prakash Thyroid Research and Practice 2019 16(3):100-104 Background: The thyroid gland, a highly vascular endocrine gland, is composed of two lateral lobes connected by isthmus. A wide range of morphological alterations of the thyroid gland such as hypoplasia, ectopy to hemiagenesis, and genesis are common because of disturbed embryogenesis. The significance of diagnosing such extensions of the thyroid gland is crucial. It may alter the normal anatomical relationship of the thyroid gland with other adjacent cervical structures. Further, it may be confused with a tumor mass on magnetic resonance imaging and scintillation scans. Methods: The primary aim is to study the thyroid gland for gross anatomical variations (weight, height, and breadth) and secondarily to document the morphometric and congenital/developmental variation gross of the thyroid gland in 65 cadavers from the coastal belt of South India. The glands were according to the various age groups of the cadavers. Results: The mean thyroid weight was 26.01 ± 7.14 g. In males, it was 26.59 ± 6.96 g, whereas in females, it was 20.93 ± 8.98 g. The pyramidal lobe was present in 35 (53.8%), and the presence of the levator glandulae thyroideae was noted in 25 (38.48%) of male cadavers. Agenesis of the isthmus was found in 20 (30.76%). However, the accessory thyroid tissue was found in only one female cadaver. Conclusions: Our morphometric study on cadaveric thyroid glands highlights individual and ethnic variations. Knowledge of various developmental anomalies and unusual variations of the thyroid gland is of paramount importance to differentiate it from other pathologies such as autonomous thyroid nodule and thyroiditis. Role of nuclear grooves in the cytological diagnosis of papillary carcinoma thyroid Archana S Bhat, Lisa Varma, Hilda Fernandes, CS Jayaprakash Thyroid Research and Practice 2019 16(3):105-107 Introduction: It is well known that nuclear grooves play a major role in the diagnosis of papillary carcinoma thyroid (PCT). Furthermore, grooves are found in many nonneoplastic lesions of thyroid. Aims: The aim of this study is to calculate the percentage of nuclear grooves in histopathologically proven cases of papillary carcinoma and nonneoplastic lesions (Hashimoto's thyroiditis and colloid goiter). Materials and Methods: This retrospective study was carried out by reviewing the data and cytology smears of 21 histopathologically confirmed cases of PCT and 10 cases each of Hashimoto's thyroiditis and colloid goiter. The percentage of nuclear grooves was calculated in oil immersion by counting 100–500 cells depending on the cellularity. Results: The percentage of nuclear grooving ranged from 15% to 85% in the papillary carcinoma cases. Greater than 20% nuclear grooves were observed in 19 (90.4%) of the cases. Nuclear crowding and overlapping, pale chromatin, nuclear grooves, nuclear enlargement, and prominent nucleoli were seen in all (100%) cases. Intranuclear cytoplasmic pseudoinclusions were seen in only 5 (23.8%) of the cases. Histiocytes, metaplastic cells, and multinucleated giant cells were seen in 12 (57.1%), 10 (47.6%), and 6 (28.5%) of the cases. The percentage of nuclear grooves in nonneoplastic cases overall observed was <10%. The sensitivity and specificity of grooves for PCT at ≥20% were 90.5% and 100%, respectively. Conclusion: Whenever in doubt, a diagnosis of papillary carcinoma can be offered confidently by this semiquantitative approach for grooves in combination with other features. Iodine nutrition status in Graves' disease: A single-center study from Bangladesh Md Abu Jar Gaffar, A B. M. Kamrul-Hasan, Afsar Ahammed, Muhammad Abul Hasanat, Md Fariduddin Thyroid Research and Practice 2019 16(3):108-112 Context: An increase in occurrence of Graves' disease (GD) has been reported in many countries after the introduction of the salt iodization program. Aims: To observe iodine nutrition status in GD. Settings and Design: Cross-sectional observational study conducted in the Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from May 2013 to September 2014. Methods and Material: This study included 140 GD patients (55 newly detected, 85 already under treatment). Urinary iodine concentration (UIC) was measured in spot urine sample following wet digestion method. The iodine nutrition status was categorized according to the internationally recommended cutoffs of UIC (excessive: ≥300 μg/L, more than optimal: 200-299 μg/L, optimal: 100-199 μg/L, deficiency: <100 μg/L). Results: The median UIC in subjects with Graves' disease was 96.69 μg/L. 21.2% of the study subjects had iodine status to be considered as more than optimal or excessive, 25.7% had optimal iodine level, and more than half (51.4%) had iodine deficiency. The mean UIC were similar in newly diagnosed and treated groups, and among subjects with different thyroid functional status. UIC did not differ among male and female subjects and among subjects from different socioeconomic groups. UIC showed no correlations with age, socioeconomic condition, the family history of thyroid disease, TSH, FT4, and thyroid function status of the study participants. Conclusions: Effective monitoring of salt iodization program is needed to prevent iodine-excess related increase in the prevalence of Graves' disease. Prognostic efficacy of thyroid profile with sequential organ failure assessment score in predicting mortality in intensive care unit patients Arvind Mishra, Rohin Saini, Madhukar Mittal, Dandu Himanshu, Kamlesh Kumar Gupta, Abbas Ali Mahdi Thyroid Research and Practice 2019 16(3):113-120 Introduction and Objectives: Thyroid hormone changes in critically ill patients are commonly observed phenomenon. This is known as sick euthyroid syndrome. Sequential organ faillure assessment (SOFA) score is used to track and determine the extent of a person's organ function or its rate of failure. We performed a prospective observation study to analyze the prognostic rather than diagnostic efficacy of thyroid function test (TFT) (T3, T4, thyroid-stimulating hormone [TSH], free triiodothyronine [fT3], and free thyroxine [fT4]) in unselected critically ill patients and compare the prognostic efficacy of fT3, fT4, TSH, T3, and T4 with SOFAS in predicting mortality in critically ill patients. Materials and Methods: We studied a sample of unselected 338 patients admitted in the intensive care unit (ICU) and measured their TFT, routine biochemical parameters within 48 h of admission along with SOFA scores and assessed their individual and combined efficacy in predicting mortality. All patients with known thyroid illness were excluded from this study. Results: There were 200 survivors and 138 nonsurvivors, the nonsurvivors had higher SOFAS score and lower free T3 levels and lower T3 levels compared to survivors. ICU survival was predicted using SOFAS score alone and a combination of TFT with SOFA score. Conclusions: In critically ill patients with higher SOFA score, lower values of serum fT3 and T3 levels were clinically significantly associated with mortality and free T3 have additional powers to improve predictive ability to SOFAS in predicting mortality in ICU patients. Severe hypothyroidism-associated acute renal failure – A case series from North India and review of literature Namrata S Rao, Abhilash Chandra, Kiran Preet Malhotra Thyroid Research and Practice 2019 16(3):121-127 Background: Several cases of complete or partially reversible renal failure have been reported in association with severe hypothyroidism, which have responded to thyroxine replacement. However, its risk factors, pathology, pathophysiology, and time of recovery remain unclear. Aim: We report our experience with 31 cases of renal failure in association with severe hypothyroidism, from a goiter-endemic belt in North India, along with a review of existing literature. Materials and Methods: We retrieved cases presenting to our centre, from August 2013 to April 2018 and collected information regarding clinical presentation, laboratory parameters including renal and thyroid function tests, creating kinase, urinary findings and follow-up data pertaining to time and extent of renal function recovery. In three cases, renal biopsies were also done, and these were reviewed by a pathologist. Results: In our study, females slightly outnumber males. More than one-third of patients were known hypothyroid and had defaulted on medications. The severity of serum thyroid-stimulating hormone and CK elevation were not associated with the severity of renal failure or its extent or time of recovery. Older age, coexistence of diabetes mellitus and/or hypertension, higher serum creatinine at presentation, and urinary abnormalities (proteinuria and/or active sediments) correlated significantly with lack of complete renal recovery. All the three biopsies revealed significant tubulointerstitial fibrosis. Conclusions: Thyroid function tests should be performed in the evaluation of unexplained renal failure, even in cases with underlying chronic kidney disease. It is also an important preventable cause of renal failure in known hypothyroid patients. A case-based approach to aggressive variants of papillary thyroid carcinoma with literature review Joseph Antoine Flordelis Chatto, Annette Laurente Salillas Thyroid Research and Practice 2019 16(3):128-136 Papillary thyroid caarcinoma (PTC) is the most common thyroid and endocrine malignancy. Although considered to be indolent, aggressive variants have been identified, including the Tall Cell (TCV), Columnar Cell (CCV), Hobnail (HPTC) and Solid Variants (SVPTC). The objective of this study is to pre-operatively recognize the cytologic features of these variants. Four cases with final diagnoses of TCV, CCV, HPTC and SVPTC were reviewed and compared with Fine Needle Aspiration Biopsy (FNAB) smears. The first case is a 44-year-old female diagnosed with TCV pre-operatively through FNAB and was confirmed through tissue biopsy showing malignant glands in papillary formation with greater than 50% of tall cells. The second patient is a 54-year-old female with CCV showing stratified columnar cells with cytoplasmic supranuclear and subnuclear vacuoles. Third is a 57-year-old female with HPTC exhibiting eccentrically-located nuclei imparting a hobnail appearance with cellular dyscohesiveness. The fourth case is a 59-year-old female diagnosed with SVPTC showing predominantly solid sheets surrounded by thin, delicate fibrous stroma. They all have nuclear features of PTC. TCV, CCV, HPTC and SVPTC are related to extrathyroidal extension, angiolymphatic invasion, positive surgical margin and lymph node metastasis. FNAB is an important tool to recognize these variants preoperatively and plan for amore comprehensive management. Extensive squamous metaplasia in papillary carcinoma of the thyroid: A potential diagnostic pitfall Subhash Yadav, Rajiv Kumar, Munita Bal, Asawari Patil Thyroid Research and Practice 2019 16(3):137-139 It is a rare event to find squamous cells in the thyroid gland. Squamous metaplasia (SM) of the thyroid follicular epithelium is one of such conditions. SM can occur in association with nonneoplastic as well as neoplastic thyroid lesions. Here, we report a case of papillary carcinoma of the thyroid in a 26-year-old female showing extensive SM. On immunohistochemistry, squamous as well as papillary carcinoma component expresses CK7 and thyroglobulin. High molecular weight cytokeratin and p63 were positive in only in the squamous area, while TTF-1 was negative in these cells. Extensive SM in the thyroid can be misinterpreted as primary or metastatic squamous cell carcinoma. Further, the tumor may be mislabeled as collision tumors of thyroid. As it might lead to therapeutic implications, the distinction of SM in thyroid is necessary. Diagnostic issue and caveats of immunoreactivity for Ki67 in hyalinizing trabecular neoplasm with a review of literature Veer Karuna, Priya Gupta, Mamta Gupta, Kriti Grover Thyroid Research and Practice 2019 16(3):140-143 Few benign and malignant tumors of thyroid lesion share many histological features, including papillary and trabecular pattern, hyalinized stroma, calcification, nuclear grooving, and nuclear inclusion. The lesions those have these common features are hyalinizing trabecular tumor, papillary thyroid carcinoma, medullary carcinoma, paraganglioma, trabecular follicular adenoma (TFA), and poorly differentiated tumor (PDT). These tumors are derived from thyroid follicular cell except PDT and paraganglioma. Hyalinized trabecular tumor and TFA are rare tumors. Due to these common features, they create a diagnostic pitfall for a false-positive or false-negative diagnosis. Therefore, histopathological and immunohistochemical studies are needed to make a definite diagnosis. The present case describes a relatively rare thyroid tumor – hyalinizing trabecular tumor – with its varied morphological features creating diagnostic difficulties and role of immunohistochemistry in formulating definitive diagnosis.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Standard safety policy: a retrospect of the Korean chicken egg crisis in 2017 Abstract On August 14, 2017, a report released by the Ministry of Agriculture, Food, and Rural Affairs confirmed the presence of pesticides in chicken eggs in South Korea. The literature has identified various causes for the crisis, such as the lack of criteria for permissible amounts of residual pesticides, and dichotomized management and supervision systems. This study investigated current laws and enactments relevant to South Korea's 2017 crisis of pesticide-contaminated eggs, seeking to extract applicable safety standards. Of the 12 laws directly related to eggs, eight contained a combined total of 19 safety standards. The main problems of these standards include the lack of criteria to regulate permissible amounts of residual pesticides, the lack of standardized countermeasures against residual chemicals, conflicting standards between higher-ranking and lower-ranking legal norms, and confusing misuse of terminology. It is suggested that these problems in egg-related safety standards can be addressed by South Korea adopting the internationally recognized Codex Alimentarius standard, with strengthened application of stricter administrative measures exceeding the Maximum Residue Levels in the field, using unified terminology. Thus, the present study aims to investigate the 2017 crisis to extract safety standards from the law and analyze related problems. The study also makes suggestions to improve applicable safety standards in the hope of preventing the recurrence of similar crises. PAGIF method to verify animal species in dairy products: improved separation performance, sensitivity and efficiency Abstract Over more than 20 years, isoelectric focusing (IEF) in a polyacrylamide gel (PAGIF) has been the only official method in Germany to verify the animal species in dairy products, including cheese. The method remains valid until now, using the analytical standards and the detection and quantification limits of that time. With the introduction of faster, cheaper and more sensitive methods, the PAGIF is in danger to lose importance in food control. Therefore, based on the § 64 method(s) of the German Food and Feed Code (LFGB), the pH gradient has been optimized, on the one hand, to sharpen the protein bands and thus to improve the detection limit (cow's milk: 0.1%, previously 1%) and on the other hand, to make it possible to analyze simultaneously several animal species, such as cow, sheep, goat and buffalo in one single gel. By condensing the workflow and improving the original performance data, the revised PAGIF will continue to be the official method in food control alongside new analytical methods. Prevalence of Salmonella spp. in Egyptian dairy products: molecular, antimicrobial profiles and a reduction trial using d -tryptophan Abstract The study aims to determine the prevalence and serotypes of Salmonella spp. in milk and dairy products sold on Egyptian markets, characterize their virulence-associated genes, and assess their antimicrobial profile. Furthermore, d-tryptophan was used as a new approach for controlling the growth of Salmonella in combination with heat stress. A total of 125 samples (raw market milk, bulk tank milk, Kareish cheese, white soft cheese, and small scale ice cream, 25 each) were used for assessing the prevalence of Salmonella spp. Nine Salmonella isolates with different serotypes were recovered from bulk tank milk (4/9; 44.44%) and Kariesh cheese (5/9; 55.55%), respectively. Antimicrobial susceptibility testing indicated that all isolates were resistant to streptomycin and erythromycin. PCR analysis revealed that 100%, 66.67% and 88.89% of the obtained isolates possessed invA, avrA and stn genes, respectively. d-Tryptophan (40 mM) in combination with heat stress had a significant inhibitory effect on Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) added to control milk samples. The results indicate insufficient hygienic measures adopted during handling by dairies in Egypt. Therefore, strict hygienic approaches are recommended during milking, processing and distribution of dairy products in Egypt. A synergistic effect of d-tryptophan and heat stress is considered as a promising tool for controlling growth of Salmonella in milk. Stichprobenplanung in der Lebensmittelüberwachung: Reduktion des notwendigen Stichprobenumfangs durch Pooling Zusammenfassung Es wird ein Verfahren zur Berechnung des notwendigen Stichprobenumfangs in einem Pooling-Design zur Ermittlung des Substanzgehalts in Lebensmitteln beschrieben. Mit diesem kann die Poolgröße und die Anzahl notwendiger Messungen zur Bestimmung eines Mittelwerts mit einer vorgegebenen Konfidenzintervallbreite berechnet werden. Wie stark sich die Anzahl analytischer Messungen durch Pooling mehrerer Proben in einer Sammelprobe reduzieren lässt, hängt dabei von der Relation zwischen biologischer Varianz (Variation zwischen Proben unterschiedlichen Ursprungs) und technischer Varianz (Variation zwischen Wiederholungsmessungen) ab. Die Anwendung der Methode wird am Beispiel der Bestimmung von Dioxinen und polychlorierten Biphenylen (PCB) in Hühnereiern erläutert, kann jedoch auf andere Kontaminanten und Lebensmittel übertragen werden. Toy swords revisited: identification of additional odour-active contaminants Abstract Odorants related to offensive odours in three children's toy swords were identified and characterized by human sensory and chemical analyses. Samples were initially evaluated by a trained sensory panel. Panellists reported unpleasant smells in all samples that were dominated by mothball-like, phenolic and rubber-like notes and additionally almond-like and fatty notes. The odorants from the samples were then extracted using dichloromethane and subsequent solvent-assisted flavour evaporation distillation. Enriched distillates were then analysed by means of single and two-dimensional gas chromatography–mass spectrometry/olfactometry. An additional screening analysis for polycyclic aromatic hydrocarbons was also performed on all samples. The most predominant odorants identified in the samples were naphthalene, 1- and 2-methylnaphthalene and diverse dimethylnaphthalene isomers with gasoline-like smells. Acetophenone, with an almond-like, flowery smell, was also detected. Furthermore, the phenolic/leather-like smelling substances 3-ethylphenol, 3-hydroxyacetophenone, and 3-methoxyacetophenone were identified in one sample. Characteristics of enterotoxin-producing methicillin-resistant Staphylococcus aureus strains isolated from meat in Tehran, Iran Abstract In this study, we investigated the clonality, antibiotic susceptibility and presence of different enterotoxin genes among 49 methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from 131 fresh raw meat samples in Tehran, Iran during 2016. 47% of beef, 30% of chicken and 27% of turkey samples were MRSA positive. PhenePlate (PhP typing) revealed the presence of 12 PhP types consisting of five common types and seven single types, and 86% of the strains harbored staphylococcal cassette chromosome mec (SCCmec) type III and type 3 cassette chromosome recombinases (ccr). Moreover, SCCmec type IVa was positive in all isolates with SGA prophage types. High level resistance to ciprofloxacin, erythromycin, tobramycin and kanamycin was also observed. The rate of resistance to most of the antibiotics tested was higher in chicken samples compared to other meat samples. Out of eleven different enterotoxin genes found, sea, sek and seq were the dominant genes in all strains. Our results illustrate the presence and persistence of highly resistant clonal groups of enterotoxin-producing MRSA in meat samples. These isolates had PhP and SCCmec types and prophage patterns which were similar to the clinical isolates previously reported in Iran, supporting the notion of dissemination of the MRSA in the hospital, community, as well food products in Iran.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Understanding high ε-poly- l -lysine production by Streptomyces albulus using pH shock strategy in the level of transcriptomics Abstract ε-Poly-l-lysine (ε-PL) is a natural food preservative, which exhibits antimicrobial activity against a wide spectra of microorganisms. The production of ε-PL was significantly enhanced by pH shock in our previous study, but the underlying mechanism is poorly understood. According to transcriptional and physiological analyses in this study, the mprA/B and pepD signal transduction system was first proved to be presented and activated in Streptomyces albulus M-Z18 by pH shock, which positively regulated the transcription of ε-PL synthetase (Pls) gene and enhanced the Pls activity during fermentation. Furthermore, pH shock changed the ratio of unsaturation to saturation fatty acid in the membrane through up-regulating the transcription of fatty acid desaturase genes (SAZ_RS14940, SAZ_RS14945). In addition, pH shock also enhanced the transcription of cytochrome c oxidase (SAZ_RS15070, SAZ_RS15075), ferredoxin reductase (SAZ_RS34975) and iron sulfur protein (SAZ_RS31410) genes, and finally resulted in the improvement of cell respiratory activity. As a result, pH shock was considered to influence a wide range of proteins including regulators, fatty acid desaturase, respiratory chain component, and ATP-binding cassette transporter during fermentation. These combined influences might contribute to enhanced ε-PL productivity with pH shock. Adaptive mechanism of Acidithiobacillus thiooxidans CCTCC M 2012104 under stress during bioleaching of low-grade chalcopyrite based on physiological and comparative transcriptomic analysis Abstract Acidithiobacillus thiooxidans (A. thiooxidans) is often used for sulfur-bearing ores bioleaching, but its adaptive mechanism to harsh environments remains unclear. Here, we explored the adaptive mechanism of A. thiooxidans in the process of low-grade chalcopyrite bioleaching based on the physiology and comparative transcriptome analysis. It was indicated that A. thiooxidans maintains intracellular pH homeostasis by regulating unsaturated fatty acids, especially cyclopropane fatty acids, intracellular ATP, amino acid metabolism, and antioxidant factors. Comparative transcriptome analysis indicated that the key genes involved in sulfur oxidation, sor and soxABXYZ, were significantly up-regulated, generating more energy to resist extreme environmental stress by more active sulfur metabolism. Confocal laser scanning microscope analysis found that down-regulation of flagellar-related genes was likely to promote the biofilm formation. System-level understanding of leaching microorganisms under extreme stress can contribute to the evolution of these extremophiles via genetic engineering modification work, which further improves bioleaching in future. Enhanced production of heterologous proteins via engineering the cell surface of Bacillus licheniformis Abstract Cell surface engineering was proven as the efficient strategy for enhanced production of target metabolites. In this study, we want to improve the yield of target protein by engineering cell surface in Bacillus licheniformis. First, our results confirmed that deletions of d-alanyl-lipoteichoic acid synthetase gene dltD, cardiolipin synthase gene clsA and CDP-diacylglycerol-serine O-phosphatidyltransferase gene pssA were not conducive to cell growth, and the biomass of gene deletion strains were, respectively, decreased by 10.54 ± 1.43%, 14.17 ± 1.51%, and 17.55 ± 1.28%, while the concentrations of total extracellular proteins were improved, due to the increases of cell surface net negative charge and cell membrane permeability. In addition, the activities of target proteins, nattokinase, and α-amylase were also improved significantly in gene deletion strains. Furthermore, the triplicate gene (dltD, clsA, and pssA) deletion strain was constructed, which further led to the 45.71 ± 2.43% increase of cell surface net negative charge and 26.45 ± 2.31% increase of cell membrane permeability, and the activities of nattokinase and α-amylase reached 37.15 ± 0.89 FU/mL and 305.3 ± 8.4 U/mL, increased by 46.09 ± 3.51% and 96.34 ± 7.24%, respectively. Taken together, our results confirmed that cell surface engineering via deleting dltD, clsA, and pssA is an efficient strategy for enhanced production of target proteins, and this research provided a promising host strain of B. licheniformis for efficient protein expression. Identification and characterization of the ZRT, IRT-like protein (ZIP) family genes reveal their involvement in growth and kojic acid production in Aspergillus oryzae Abstract The ZRT, IRT-like protein (ZIP) family exists in many species and plays an important role in many biological processes, but little is known about ZIP genes in Aspergillus oryzae. Here, 10 ZIP genes in A. oryzae were identified and these were classified into four groups based on phylogenetic analysis. The structures of these AoZip genes were determined, which indicated a great divergence of AoZip members from different groups. Synteny analysis revealed that AoZip7, AoZip8, and AoZip10 are conserved among Aspergillus species. We also found that the promoter regions of AoZip2, AoZip7, AoZip8, and AoZip10 contain multiple conserved response elements. Expression analysis revealed that AoZips exhibited different expression patterns in response to different metal treatments. Moreover, overexpression and RNA-interference (RNAi) of AoZip2 led to a decrease in mycelium growth diameter and inhibited conidia formation. AoZip2 overexpression and RNAi strains showed distinct sensitivity to severely Zn/Mn-depleted stress. In addition, kojic acid production was markedly lower in AoZip2 overexpression and RNAi strains than in the control strains, and the expression of kojA, kojR, and kojT was down-regulated in AoZip2 overexpression and RNAi strains. This study provides new insights into our understanding of ZIP genes and lays a foundation for further investigation of their roles in Aspergillus oryzae. The expression, secretion and activity of the aspartic protease MpAPr1 in Metschnikowia pulcherrima IWBT Y1123 Abstract Protease-secreting yeasts have broad biotechnological potential for application to various industrial processes, including winemaking. However, this activity is influenced by the yeast response to environmental factors such as nitrogen and protein sources, as are found in grape juice. In this study, the wine-relevant yeast Metschnikowia pulcherrima IWBT Y1123, with known protease-secreting ability, was subjected to different nitrogen-containing compounds to monitor their impact on protease secretion and activity. Protease activity increased above basal levels for haemoglobin-containing treatments, indicating an inductive influence of proteins. On the other hand, treatments containing both haemoglobin and assimilable nitrogen sources led to a delayed increase in protease activity and protein degradation, suggesting a nitrogen catabolite repression mechanism at work. Protease activity and expression were furthermore evaluated in grape juice, which revealed increased expression and activity levels over time as promising results for further investigations into the impact of this yeast on wine properties. Redirecting the lipid metabolism of the yeast Starmerella bombicola from glycolipid to fatty acid production Abstract Free fatty acids are basic oleochemicals implemented in a range of applications including surfactants, lubricants, paints, plastics, and cosmetics. Microbial fatty acid biosynthesis has gained much attention as it provides a sustainable alternative for petrol- and plant oil-derived chemicals. The yeast Starmerella bombicola is a microbial cell factory that naturally employs its powerful lipid metabolism for the production of the biodetergents sophorolipids (> 300 g/L). However, in this study we exploit the lipidic potential of S. bombicola and convert it from the glycolipid production platform into a free fatty acid cell factory. We used several metabolic engineering strategies to promote extracellular fatty acid accumulation which include blocking competing pathways (sophorolipid biosynthesis and β-oxidation) and preventing free fatty acid activation. The best producing mutant (Δcyp52m1Δfaa1Δmfe2) secreted 0.933 g/L (± 0.04) free fatty acids with a majority of C18:1 (43.8%) followed by C18:0 and C16:0 (40.0 and 13.2%, respectively). Interestingly, deletion of SbFaa1 in a strain still producing sophorolipids also resulted in 25% increased de novo sophorolipid synthesis (P = 0.0089) and when oil was supplemented to the same strain, a 50% increase in sophorolipid production was observed compared to the wild type (P = 0.03). We believe that our work is pivotal for the further development and exploration of S. bombicola as a platform for synthesis of environmentally friendly oleochemicals. Microbial production of O -methylated flavanones from methylated phenylpropanoic acids in engineered Escherichia coli Abstract Methylated flavonoids possess improved bioactivities compared to their unmethylated counterparts. In this study, for the efficient production of O-methylated flavonoids from simple methylated phenylpropanoic acids, a recombinant Escherichia coli strain expressing 4-coumarate:coenzyme A ligase (4CL) from Oryza sativa and chalcone synthase (CHS) from Hordeum vulgare was constructed; this strain produced significant amount of homoeriodictyol (~ 52 mg/L) as well as a few amount of hesperetin (0.4 mg/L), respectively, from ferulic acid and 4-methylcaffeic acid. This demonstrates, for the first time, that the scarce but valuable methylated flavanones can be successfully produced from methylated phenylpropanoic acids in a microbial host via an artificial biosynthetic pathway consisting of 4CL and CHS that can accept O-methylated precursors. Beneficial mutations for carotenoid production identified from laboratory-evolved Saccharomyces cerevisiae Abstract Adaptive laboratory evolution (ALE) is a powerful tool used to increase strain fitness in the presence of environmental stressors. If production and strain fitness can be coupled, ALE can be used to increase product formation. In earlier work, carotenoids hyperproducing mutants were obtained using an ALE strategy. Here, de novo mutations were identified in hyperproducers, and reconstructed mutants were explored to determine the exact impact of each mutation on production and tolerance. A single mutation in YMRCTy1-3 conferred increased carotenoid production, and when combined with other beneficial mutations led to further increased β-carotene production. Findings also suggest that the ALE strategy selected for mutations that confer increased carotenoid production as primary phenotype. Raman spectroscopy analysis and total lipid quantification revealed positive correlation between increased lipid content and increased β-carotene production. Finally, we demonstrated that the best combinations of mutations identified for β-carotene production were also beneficial for production of lycopene. Efficient production of glutathione with multi-pathway engineering in Corynebacterium glutamicum Abstract Glutathione is a bioactive tripeptide composed of glycine, l-cysteine, and l-glutamate, and has been widely used in pharmaceutical, food, and healthy products. The current metabolic studies of glutathione were mainly focused on the native producing strains with precursor amino acid supplementation. In the present work, Corynebacterium glutamicum, a workhorse for industrial production of a series of amino acids, was engineered to produce glutathione. First, the introduction of glutathione synthetase gene gshF from Streptococcus agalactiae fulfilled the ability of glutathione production in C. glutamicum and revealed that l-cysteine was the limiting factor. Then, considering the inherent capability of l-glutamate synthesis and the availability of external addition of low-cost glycine, l-cysteine biosynthesis was enhanced using a varieties of pathway engineering methods, such as disrupting the degradation pathways of l-cysteine and l-serine, and removing the repressor responsible for sulfur metabolism. Finally, the simultaneously introduction of gshF and enhancement of cysteine formation enabled C. glutamicum strain to produce glutathione greatly. Without external addition of l-cysteine and l-glutamate, 756 mg/L glutathione was produced. This is first time to demonstrate the potential of the glutathione non-producing strain C. glutamicum for glutathione production and provide a novel strategy to construct glutathione-producing strains. Biological functions of nirS in Pseudomonas aeruginosa ATCC 9027 under aerobic conditions Abstract Through our previous study, we found an up-regulation in the expression of nitrite reductase (nirS) in the isothiazolone-resistant strain of Pseudomonas aeruginosa. However, the definitive molecular role of nirS in ascribing the resistance remained elusive. In the present study, the nirS gene was deleted from the chromosome of P. aeruginosa ATCC 9027 and the resulting phenotypic changes of ΔnirS were studied alongside the wild-type (WT) strain under aerobic conditions. The results demonstrated a decline in the formations of biofilms but not planktonic growth by ΔnirS as compared to WT, especially in the presence of benzisothiazolinone (BIT). Meanwhile, the deletion of nirS impaired swimming motility of P. aeruginosa under the stress of BIT. To assess the influence of nirS on the transcriptome of P. aeruginosa, RNA-seq experiments comparing the ΔnirS with WT were also performed. A total of 694 genes were found to be differentially expressed in ΔnirS, of which 192 were up-regulated, while 502 were down-regulated. In addition, these differently expressed genes were noted to significantly enrich the carbon metabolism along with glyoxylate and dicarboxylate metabolisms. Meanwhile, results from RT-PCR suggested the contribution of mexEF-oprN to the development of BIT resistance by ΔnirS. Further, c-di-GMP was less in ΔnirS than in WT, as revealed by HPLC. Taken together, our results confirm that nirS of P. aeruginosa ATCC 9027 plays a role in BIT resistance along with biofilm formation and further affects several metabolic patterns under aerobic conditions.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Deoxyribonucleic Acid Repair Activity Is Associated with Healed Coronary Plaque Rupture by Optical Coherence Tomography Abstract Deoxyribonucleic acid (DNA) damage and repair signaling cascades are related to the development of atherosclerosis. Pathological studies have demonstrated that healed coronary plaque rupture (HCPR) contributes to plaque progression and predisposes to sudden ischemic cardiac death. The objective of this study is to investigate the relationship between HCPR detected by optical coherence tomography (OCT) and DNA ligase. Forty-two patients with both OCT and DNA ligase were prospectively enrolled. The population included patients with stable angina pectoris (SA) and non-ST-elevation myocardial infarction (NSTEMI). It was found that the prevalence of HCPR was greater in subjects with higher DNA ligase activity (correlation coefficient 0.36, p = 0.019). The presence of HCPR in patients with NSTEMI was greater than in patients with SA per OCT analysis; however, there was no statistical difference in this limited population (22.53% versus 12.83%, respectively, p = 0.116). DNA repair activity by DNA ligase was associated with HCPR in advanced coronary artery plaque by OCT. Amyloid Cardiomyopathy in the Rare Transthyretin Tyr78Phe Mutation Abstract Tyr78Phe is a rare pathogenic transthyretin (TTR) mutation. Few previous reports described a late-onset hereditary transthyretin-related amyloidosis (ATTR-m) form with a variable phenotype, mainly dominated by neurological manifestations. We describe the case of a 69-year-old male with massive but asymptomatic cardiac infiltration and only subclinical neurological involvement, and review the literature to depict characteristics of the Tyr78Phe TTR mutation. Application of Proteomics Profiling for Biomarker Discovery in Hypertrophic Cardiomyopathy Abstract High-throughput proteomics profiling has never been applied to discover biomarkers in patients with hypertrophic cardiomyopathy (HCM). The objective was to identify plasma protein biomarkers that can distinguish HCM from controls. We performed a case-control study of patients with HCM (n = 15) and controls (n = 22). We carried out plasma proteomics profiling of 1129 proteins using the SOMAscan assay. We used the sparse partial least squares discriminant analysis to identify 50 most discriminant proteins. We also determined the area under the curve (AUC) of the receiver operating characteristic curve using the Monte Carlo cross validation with balanced subsampling. The average AUC was 0.94 (95% confidence interval, 0.82–1.00) and the discriminative accuracy was 89%. In HCM, 13 out of the 50 proteins correlated with troponin I and 12 with New York Heart Association class. Proteomics profiling can be used to elucidate protein biomarkers that distinguish HCM from controls. Oxidized HDL, as a Novel Biomarker for Calcific Aortic Valve Disease, Promotes the Calcification of Aortic Valve Interstitial Cells Abstract Calcific aortic valve disease (CAVD) is characterized by progressive mineralization of the aortic valve. Lipid infiltration and oxidative stress are the driving forces for the initiation and development of this disease. However, it remains unknown whether oxidized high-density lipoprotein (ox-HDL) plays a role in the mineralization of aortic valve interstitial cells (AVICs). Serum ox-HDL levels were determined in 168 severe CAVD patients and 168 age- and gender-matched non-CAVD controls. Results showed that ox-HDL concentrations were significantly increased in CAVD compared with the control group (131.52 ± 30.96 ng/mL vs. 112.58 ± 32.20 ng/mL, P < 0.001) and were correlated with CAVD severity. Multivariable logistic regression revealed that ox-HDL levels were independently associated with CAVD after adjusting for the incidence of coronary artery disease (CAD) (odds ratio 1.019, 95% CI 1.012–1.027, P < 0.001) or atherosclerotic risk factors (odds ratio 1.027, 95% CI 1.017–1.037, P < 0.001). Chronic ox-HDL stimulation of AVICs increased alkaline phosphatase activity (ALP) and calcium deposits in AVICs in vitro. Mechanistic studies further showed that ox-HDL upregulated several osteogenic factors, including BMP-2, Runx2, and Msx2 expressions in AVICs. This is the first study to demonstrate a relationship between increased ox-HDL concentration and CAVD incidence. Exercise Attenuates Acute β-Adrenergic Overactivation – Induced Cardiac Fibrosis by Modulating Cytokines Abstract During acute sympathetic stress, the overactivation of β-adrenergic receptors (β-ARs) causes cardiac fibrosis by triggering inflammation and cytokine expression. It is unknown whether exercise training inhibits acute β-AR overactivation–induced cytokine expression and cardiac injury. Here, we report that running exercise inhibited cardiac fibrosis and improved cardiac function in mice treated with isoproterenol (ISO), a β-AR agonist. A cytokine antibody array revealed that running exercise prevented most of the changes in cytokine expression induced by ISO. Specifically, ISO-induced upregulation of 18 cytokines was prevented by running exercise. A Kyoto encyclopedia of genes and genomes analysis of these cytokines revealed that Hedgehog and RAP1 signaling pathways were involved in the regulation of cytokine expression by exercise. The changes in the expression of some cytokines that were prevented by exercise were verified by an enzyme-linked immunosorbent assay and real-time PCR. In conclusion, running exercise prevented the cytokine expression changes after acute β-AR overactivation and therefore attenuated cardiac fibrosis. Acute sympathetic stress is an important risk factor for the patients with cardiovascular diseases, and the present study revealed that exercise training can prevent against the upregulation of cytokines and the subsequent cardiac injury induced by acute sympathetic stress, suggesting that exercise training may be beneficial for cardiovascular patients who are in risk of acute sympathetic stress. This finding provides a theoretical basis for the application of exercise training in patients who may suffer from acute sympathetic stress. 3D Myocardial Scar Prediction Model Derived from Multimodality Analysis of Electromechanical Mapping and Magnetic Resonance Imaging Abstract Many cardiac catheter interventions require accurate discrimination between healthy and infarcted myocardia. The gold standard for infarct imaging is late gadolinium–enhanced MRI (LGE-MRI), but during cardiac procedures electroanatomical or electromechanical mapping (EAM or EMM, respectively) is usually employed. We aimed to improve the ability of EMM to identify myocardial infarction by combining multiple EMM parameters in a statistical model. From a porcine infarction model, 3D electromechanical maps were 3D registered to LGE-MRI. A multivariable mixed-effects logistic regression model was fitted to predict the presence of infarct based on EMM parameters. Furthermore, we correlated feature-tracking strain parameters to EMM measures of local mechanical deformation. We registered 787 EMM points from 13 animals to the corresponding MRI locations. The mean registration error was 2.5 ± 1.16 mm. Our model showed a strong ability to predict the presence of infarction (C-statistic = 0.85). Strain parameters were only weakly correlated to EMM measures. The model is accurate in discriminating infarcted from healthy myocardium. Unipolar and bipolar voltages were the strongest predictors. Early Wave Reflection and Pulse Wave Velocity Are Associated with Diastolic Dysfunction in Rheumatoid Arthritis Abstract Rheumatoid arthritis (RA) impacts arterial and diastolic function. This study examined whether arterial properties can determine diastolic function in RA. In 173 RA patients, arterial function measures including carotid femoral pulse wave velocity (PWV), central systolic and pulse pressure, pulse pressure amplification, and the magnitude and timing of the forward and reflected waves were measured using applanation tonometry. Diastolic function parameters including the ratio of early-to-late transmitral velocity (E/A) and ratio of E to the mean of the lateral and septal wall myocardial tissue lengthening (e') were measured using echocardiography. The timing of the reflected wave was associated with E/A; PWV was related to E/e'. The timing of the reflected wave, forward wave magnitude, and pulse pressure amplification were associated with impaired relaxation; PWV was related to increased left ventricular (LV) filling pressure. Early wave reflection and PWV are associated with LV-impaired relaxation and increased filling pressure, respectively, in RA. Prevalence of Cardiac Amyloidosis in Patients with Carpal Tunnel Syndrome Abstract Carpal tunnel syndrome (CTS) is a common finding among patients with cardiac amyloidosis. We sought to determine the prevalence of cardiac amyloidosis in patients who had undergone CTS surgery. From 2005 to 2014, 308 patients ≥ 60 years underwent CTS surgery. Of these, 233 (76%) agreed to participate in the study and 101 (73 ± 8 years; 68% females) showed left ventricular hypertrophy (LVH) ≥ 12 mm and underwent additional studies to diagnose AL and ATTR amyloidosis. Based on complementary studies, three patients were diagnosed with cardiac amyloidosis (two wild-type ATTR and one AL). The three patients showed bilateral CTS with no occupational risk factors. Prevalence of cardiac amyloidosis in the overall cohort was only 1.2% (3/233), but among patients with LVH and bilateral CTS, the prevalence was 5.5% (3/55) and 13.6% (3/22) if cases with an occupational risk factor were excluded. Cardiac amyloidosis should be excluded in the presence of bilateral CTS and particularly if an occupational risk factor is absent. The Influence of Aortic Valve Obstruction on the Hyperemic Intracoronary Physiology: Difference Between Resting Pd/Pa and FFR in Aortic Stenosis Abstract The reliability of fractional flow reserve (FFR) in aortic stenosis (AS) has been questioned because of the uncertain response to vasodilators. A retrospective multicenter cohort of 114 AS patients who underwent coronary physiology assessment was compared with 154 controls before and after propensity matching adjustment. The difference between resting distal coronary vs aortic pressure ratio (Pd/Pa) and FFR (ΔPd/Pa-FFR) was tested against the severity of AS. ΔPd/Pa-FFR was not influenced by the severity of AS in terms of aortic valve area (r = − 0.02, p = 0.83) and gradient (r = − 0.05, p = 0.64) or by the left ventricle hypertrophy (r = − 0.03, p = 0.88). Conversely, ΔPd/Pa-FFR was influenced by the presence of diabetes (r = − 0.24, p = 0.005), peripheral vascular disease (r = − 0.16, p = 0.047), and chronic kidney disease (r = − 0.19, p = 0.03). No significant difference was observed in the ΔPd/Pa-FFR between patients with AS and matched controls. Further studies are warranted to validate the FFR-guided revascularization in patients with AS. Curcumin Induces Endothelium-Dependent Relaxation by Activating Endothelial TRPV4 Channels Abstract It is well-known that curcumin, as a plant substance, has vascular protective effects. TRPV4 (transient receptor potential vanilloid 4) is a highly Ca2+-selective channel in vascular endothelium. In our study, fluorescent Ca2+ imaging in mesenteric arterial endothelial cells (MAECs) and overexpressed TRPV4 human embryonic kidney (HEK293) cells showed that curcumin dose-dependently stimulated Ca2+ influx. Whole-cell patch clamp proved that curcumin stimulated the TRPV4-mediated currents in TRPV4-HEK293 cells. The TRPV4-specific blocker HC067047 markedly decreased the whole-cell current. Molecular modeling and docking showed that the binding site of curcumin and TRPV4 was mainly in the amino acid sequence LYS340-LEU349 of TRPV4 protein. Furthermore, curcumin dose-dependently induced the endothelium-dependent vessel dilatation in small mesenteric arteries. Therefore, our results demonstrated that curcumin stimulates Ca2+ entry in endothelial cells and improves endothelium-dependent vessel relaxation by activating TRPV4 channels. Moreover, we identified the specific binding sites of curcumin and TRPV4, thereby highlighting its potential therapeutic target of cardiovascular diseases.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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The utility of thromboelastography and tranexamic acid in plasminogen activator inhibitor deficiency during pregnancy: a rare case report Complete plasminogen activator inhibitor-1 (PAI-1) deficiency is a very rare genetic disorder that is associated with an increased risk of bleeding diathesis. Patients with PAI-1 deficiency are also known to be at increased risk for massive postpartum hemorrhage. We discuss one such rare case of PAI-1 deficiency in a young pregnant patient at 22 weeks of gestation with history of prolonged bleeding. Tranexamic acid was administered for menorrhagia and resumed later for labor and continued into the postpartum period since antifibrinolytics have been the mainstay in the management of PAI-1 deficiency. The patient delivered a healthy infant at 39 weeks. As PAI-1 deficiency causes increased fibrinolysis, the patient's coagulation panel was monitored by performing serial thromboelastograms to monitor for any increase in fibrinolysis. We believe that thromboelastograms might be a useful tool in the monitoring and management of fibrinolytic conditions such as PAI-1 deficiency. Correspondence to Nitya Prabhakaran, MD, Resident, Post Graduate Year 4, Pathology and Anatomic Sciences, Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, M263 Medical School Building, One Hospital Drive, Columbia, MO 65212, USA Tel: +1 573 882 1201; e-mail: prabhakarann@health.missouri.edu Received 29 May, 2019 Revised 21 October, 2019 Accepted 25 October, 2019 Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved. von Willebrand factor alloantibodies in type 3 von Willebrand disease The development of neutralizing antibodies is a rare complication of von Willebrand disease treatment. In major surgical procedures for severe forms of the disease, the recognition of ineffective therapy and alternative treatment protocols are lifesaving. We report the case of a 6-year-old girl with type 3 von Willebrand disease in whom inhibitors were sought due to ineffective haemostasis together with lower than expected von Willebrand factor (VWF) recoveries after a surgical procedure. Replacement therapy first with recombinant factor VIIa and then with high doses of recombinant factor VIII in continuous infusion successfully stopped the bleeding. A high level of anti-VWF antibodies was determined by the immunological method. A frameshift mutation associated with premature termination codon (c.2435delC, p.Pro812ArgfsTer31) was determined in our patient. Although the reports on association of this mutation with inhibitor risk are inconsistent, it represents an evidence-based diagnostic and management practice in recognition of high-risk VWF genotype. Correspondence to Barbara Faganel Kotnik, MD, PhD, Department of Haematology and Oncology, University Medical Centre Ljubljana, University Children's Hospital, Bohoričeva 20, 1000 Ljubljana, Slovenia. Tel: +386 1 522 9215; fax: +386 1 522 4038; e-mail: barbara.faganel@kclj.si Received 16 May, 2019 Revised 22 August, 2019 Accepted 26 September, 2019 Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved. Evaluation of biomarkers for monitoring thrombogenic potential of FXaI16L A zymogen-like activated factor X variant (FXaI16L) is being developed for treating acute bleeding conditions. Activated factor V is an essential cofactor to FXaI16L for activating prothrombin to thrombin. Thrombi/emboli formation was observed microscopically in FXaI16L toxicity studies in animals. The objective of this research was to evaluate candidate biomarkers for FXaI16L-induced thrombi/emboli formation to inform safety monitoring and dose-escalation decisions in FXaI16L clinical trials. Effects of intravenous FXaI16L administration on platelets, fibrinogen, activated partial thromboplastin time (aPTT), prothrombin time (PT), D-dimer, tissue factor pathway inhibitor, thrombin : antithrombin complex, antithrombin, and factor V, and protein C (PC) activities were evaluated in mice, rats, and monkeys. Mice had endogenous factor V activity 10× that of monkeys and were overly sensitive to FXaI16L-induced thrombi/emboli formation. In monkeys, decreases in fibrinogen and prolongation in aPTT and PT emerged as potential biomarkers for impending FXaI16L-induced thrombi/emboli formation, based on association of changes with microscopically observable thrombi/emboli (0–97 thrombi/emboli per monkey). PC decreases, measured by a clot-based assay, were also observed. A similar reduction in PC activity, when measured by clot-based assay, was observed in a phase 1 clinical trial. However, an in-vitro experiment with human plasma spiked with increasing concentrations of FXaI16L indicated dose-dependent FXaI16L-induced interference with clot-based assays and no depletion of PC or S by FXaI16L in non-clot-based assays. Nonclinical biomarker studies identified fibrinogen, aPTT and PT as potential biomarkers for monitoring the clinical safety of FXaI16L. Results of clot-based assays with FXaI16L treatment should be interpreted with caution. Correspondence to Michael W. Bolt, PhD, DABT, Drug Safety Research and Development, Pfizer Inc, 1 Portland St, Cambridge, MA 02139, USA Tel: +1 617 674 6408; e-mail: Michael.Bolt@Pfizer.com Received 3 May, 2019 Revised 27 August, 2019 Accepted 26 September, 2019 Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved. Congenital afibrinogenemia in a patient with vascular abnormalities and a novel variant: clinical-molecular description and literature review The objective is to report a patient with congenital afibrinogenemia and vascular abnormalities and also review the clinical and molecular issues. The female proband, diagnosed with congenital afibrinogenemia, was admitted at a hospital due to a hemorrhagic shock. Angiotomography revealed ectasias from ascending branch to the abdominal aorta, with multiple calcifications and atheroma. Clinical exome identified a homozygous novel pathogenic variant in FGG gene. In our review the main symptom, at diagnosis, was umbilical cord bleeding and the degree of clinical involvement varied from asymptomatic to severe. The FGA gene was the most affected and possible hot spots were observed. Variants considered as loss of function were the most frequent. The association of vascular abnormalities in a patient with congenital afibrinogenemia alerts for a closer follow-up of vascular issues in these patients. Correspondence to Luiza A. Virmond, Clinical Genetics Department, Universidade Federal de São Paulo, Rua Botucatu, 394, Vila Clementino, São Paulo 04023-061, SP, Brazil E-mail: virmondluiza@gmail.com Received 2 August, 2019 Accepted 15 October, 2019 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.bloodcoagulation.com). Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.bloodcoagulation.com). Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved. An obscure case of using apixaban anti-Xa levels in a morbidly obese patient who was nil per os with enterocutaneous fistula Apixaban anti-Xa levels have been introduced to monitor apixaban activity. Presented is a fundamental use of anti-Xa monitoring in questionable absorption in enterocutaneous fistula. A 57-year-old morbidly obese male (150 kg, BMI 42.5) presented to the emergency department with deep venous thromboses and pulmonary embolisms. He also had high-output enterocutaneous fistula managed with an abdominal collection device, total parental nutrition therapy, and nil per os status. He was able to take some oral (PO) medications; however, he reported finding whole capsules in his collection device. He refused enoxaparin injections for venous thromboembolism treatment. The decision was made to load with apixaban therapy with anti-Xa monitoring. After two 10-mg doses, peak apixaban anti-Xa level was 146 ng/ml which fell within on-therapy levels in the AMPLIFY study, prothrombin time 18 s, partial thromboplastin time 35.5 s, international normalized ration 1.5. Monitoring was an important factor in this patient with questionable absorption and further complicated by his morbid obesity which has not been adequately studied in clinical trials. Correspondence to Jennifer L. Cole, PharmD, BCPS, BCCCP, Clinical Pharmacy Specialist, Veterans Healthcare System of the Ozarks, Department of Pharmacy, 1100 North College Avenue, Fayetteville, AR 72703, USA Tel: +1 479 444 4020; e-mail: Jennifer.cole@va.gov Received 24 June, 2019 Revised 15 August, 2019 Accepted 6 October, 2019 Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved. Investigating the influence of LCT rs3754689 polymorphism on inhibitor development in Iranian and Afghan patients with severe hemophilia A Development of alloantibodies against factor VIII (FVIII) in patients with severe hemophilia A is the main complication of FVIII replacement therapy. There are many studies indicating several genetic factors associated with inhibitor development. A recent study showed that there is a correlation between the risk of inhibitor development and LCT rs3754689 polymorphism among Italian hemophilia A patients. The aim of this study was to speculate whether LCT rs3754689 polymorphism is correlated to inhibitor development in Afghan and Iranian patients. In addition, we assessed the association of F8 gene mutations and inhibitor development in Iranian patients. This case–control study was conducted on 33 severe hemophilia A patients with inhibitor and 119 samples without inhibitor. Genotyping was performed by Sanger sequencing, inverse and multiplex PCR. According to the obtained data, we found a significant correlation between LCT rs3754689 polymorphism and the risk of inhibitor development in Afghan patients (observed risk, 0.11; 95% confidence interval, 0.01–0.88; P = 0.012). Among Iranian patients, rs3754689 polymorphism showed no significant association with inhibitor development against FVIII (P > 0.05). However, we found a significant correlation between the risk of inhibitor formation and large deletions and nonsense mutations in F8 gene among Iranian patients (observed risk, 7.25; 95% confidence interval, 1.93–27.18; P = 0.003). Lack of association of rs3754689 polymorphism in Iranian population shows the various effects of genetic markers in different populations. More studies in different ethnicities or larger sample sizes are recommended. Correspondence to Sirous Zeinali, Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran; Dr Zeinali's Medical Genetics Laboratory, Kawsar Human Genetics Research Center, Tehran, Iran; Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran E-mail: zeinali@kawsar.ir Received 18 June, 2019 Revised 29 August, 2019 Accepted 26 September, 2019 Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved. Thrombin generation test with the calibrated automated thrombogram and anticoagulant activity of Mentha crispa Evaluate the in-vitro effect of Mentha crispa extract on blood coagulation, compare the conventional coagulometric tests with thrombin generation test (TGT), and study the qualitative micromolecular composition of M. crispa. Extract of M. crispa was incubated with plasma and used in the coagulometric tests: prothrombin and activated partial thromboplastin times, fibrinogen, and TGT. A phytochemical prospection was performed to evaluate the chemical composition of this extract. The extract was efficient in prolonging prothrombin time and activated partial thromboplastin time, and reducing fibrinogen levels and TGT parameters, indicating that the extract of M. crispa inhibited the intrinsic and extrinsic pathways of blood coagulation. The results obtained in TGT are in agreement with the results of conventional coagulometric tests and the in-vitro anticoagulant activity of M. crispa suggests that its use by patients using oral anticoagulants deserves caution. Correspondence to Paula M. Leite, Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Belo Horizonte, Minas Gerais, Brazil. Tel: +55 31 3409 6936; fax: +55 31 3409 6935; e-mail: paulamleite02@gmail.com; ORCID ID 0000-0002-8499-5791 Received 27 June, 2019 Revised 13 September, 2019 Accepted 26 September, 2019 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.bloodcoagulation.com). Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Comparing Nonopioids Versus Opioids for Acute Pain in the Emergency Department: A Literature Review Background: Pain is the most common reason for patient visits in the emergency department (ED). Opioids have been long considered the standard of care for acute pain in the ED. Because of the opioid crisis, investigation and implementation of novel practices to manage pain is needed. The use of various nonopioids has been suggested as a plausible alternative to opioids, with emerging literature to support its use for acute pain in the ED. Study Question: To evaluate the safety, efficacy, opioid-sparing effects of nonopioids in patients who present with acute pain in the ED. Data Sources: We systematically searched PubMed and EMBASE (July 1970 to January 2019). Study Design: Randomized controlled trials that evaluated nonopioids versus opioids in the ED were eligible. The clinical outcomes measured were change in pain scores compared with baseline, the incidence of adverse events, and use of rescue analgesia. Results: Twenty-five randomized controlled trials that evaluated the use of nonopioids in 2323 patients [acetaminophen (APAP) (n = 651), diclofenac (n = 547), ketamine (n = 272), ketorolac (n = 225), lidocaine (n = 219), ibuprofen (n = 162), ibuprofen & APAP (n = 162), hydroxyzine & dihydroergotamine (n = 85)] met inclusion criteria. Four trials found significant greater reductions in pain scores, favoring nonopioids. In all trials, the duration of pain relief provided by nonopioids was not sustained over an extended period. Eighteen trials reported no significant differences in reduction of pain scores. Two trials reported improved pain reduction with opioids and one trial reported noninferiority. Conclusions: Evidence from primary literature suggests that nonopioids could be a feasible alternative to opioids for management of acute pain in the ED as it is effective, safe, and decreases the need for rescue analgesia. Address for correspondence: Assistant Director of Pharmacy, Mount Sinai Queens, Long Island City, Queens NY, 25–10 30th Avenue, Long Island City, NY 11102. E-mail: billy.sin@mountsinai.org The authors have no conflicts of interest to declare. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.americantherapeutics.com). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. Acetazolamide-Associated Hyperosmolar Hyperglycemic Nonketotic Syndrome No abstract available Carfilzomib-Induced Pulmonary Hypertension No abstract available Inappropriate Use of Aztreonam Background: Aztreonam is not a preferred empiric antibiotic because of variable susceptibilities compared with alternative agents. In addition, it has no Gram-positive activity, necessitating coadministration with vancomycin when used empirically, and is more costly when compared with other Gram-negative active agents. Aztreonam is often given to patients with a reported penicillin allergy without further investigation into the reaction or other relevant allergy information. Study Question: How frequently is aztreonam being used inappropriately? Study Design: We conducted a retrospective chart review at an academic medical center to assess the appropriateness of our aztreonam use. Measures and Outcomes: Our primary outcome was frequency of appropriate aztreonam use, based on a true IgE-mediated allergy reported for each patient. We evaluated whether the patients had tolerated a beta-lactam in the past, and what the reported allergic reaction was. Results: We included 165 patients and found that 46.7% of our aztreonam use was inappropriate, based on previous use of a beta-lactam, or no documentation of an IgE-mediated response. Of the patients with a documented beta-lactam allergy, 63 (38.2%) patients had no allergy manifestation listed, and 37 (22.4%) patients had a non–IgE-mediated allergy manifestation. Of the total population, 61 (37%) patients had tolerated a beta-lactam in the past. Conclusions: Aztreonam should be avoided, except in the case of a true IgE-mediated allergic reaction. Our goal was to reduce the inappropriate use of aztreonam at our institution by one or more of the following: educating providers, reviewing aztreonam orders, requiring answering of order questions, or requiring an indication for use. Penicillin skin testing and desensitization are options as well. Address for correspondence: 600 S 43rd Street, 108T, Philadelphia, PA 19104. E-mail: mking3509@gmail.com L. Rose is on the speakers' bureau for Allergan. M. King is on the speakers' bureau for Tetraphase. The remaining authors have no conflicts of interest to declare. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. Hundred Years of Insulin Therapy: Purified Early Insulins Background: The discovery of insulin has changed dramatically the outcome of patients with type 1 diabetes, giving them the possibility to survive. This is of particular concern due to the fact that type 1 diabetes most frequently occurs in children who were destined to die in ketoacidosis coma. Areas of Uncertainty: From insulin discovery to the availability of human insulin and human insulin analogs to be used in diabetes therapy, a series of problems have arisen as the difficulty of insulin purifications, the animal insulin used by the first researches were in fact contaminated by proteins, fats, and other impurities, and the presence of side effects such as allergy, antibodies generation, and lipoatrophy. Data Source Literature: Data strictly related to the argument have been searched in Pub Med and used. Results: Starting from insulin discovery in 1921 to nowadays, significant efforts have been made by a series of researches to purify animal insulin, discover the molecular structure of human insulin, and develop methods to synthetize human insulin and then insulin analogs. Conclusions: The history of insulin discovery here reported is fascinating; insulin is a hormone, a product of biotechnology, a field of research that saved and save the life of many diabetic patients. Address for correspondence: E-mail: annunziata.lapolla@unipd.it The authors have no conflicts of interest to declare. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. Examining the Causes and Consequences of Increasing Insulin Costs With Prospective Interventions No abstract available Paliperidone-Associated Priapism in an Autistic Child No abstract available Cefepime-Associated Myoclonic Seizures No abstract available Angioedema in an Immunocompromised Patient No abstract available Insulin Therapy and Diabetic Pregnancy Background: A good metabolic control before conception and throughout pregnancy with diabetes decreases the risk of short- and long-term adverse outcomes of the mothers and their offsprings. Insulin treatment remains the gold standard treatment recommended for any type of diabetes. New technologies including new insulins and insulin analogues, continuous subcutaneous insulin infusion without and with sensors, the low-glucose predictive suspension function, and closed-loop systems that persistently and automatically self-adjust according to patients' continuous glucose monitoring readings have expanded the offer to clinicians for achieving tight glucose control. Areas of Uncertainty: Unsafe effects of insulin and insulin analogues in pregnancy with diabetes could be linked with changes in insulin immunogenicity, teratogenicity, and mitogenicity. Second-generation insulin analogues need to be tested and proven. Effectiveness and safety of new insulin delivery systems in real life of diabetic women in pregnancy need further confirmations. Sources: MEDLINE, EMBASE, Web of Science, Cochrane Library, randomized controlled trials, systematic review and meta-analysis, observational prospective and retrospective studies, case series reports for the most recent insulin analogues, published in English impacted journals, and consensus statements from scientific societies I excluded 60 from 221 papers as not suitable for the purpose of the subject. Results: Subcutaneous insulin infusion can be safely used during pregnancy and delivery of well-trained women. Sensors are increasingly accurate tools that improve the efficacy and safety of integrated systems' functioning. Continuous glucose monitoring provides metrics ("time in range" time in "hypoglycemia" and in "hyperglycemia," glucose variability, average glucose levels in different time intervals) used as a guide to diabetes management; these new metrics are object of discussion in special populations. Randomized controlled trials have shown that sensor-augmented pump therapy improves pregnancy outcomes in women with type 1 diabetes. Closed-loop insulin delivery provides better glycemic control than sensor-augmented pump therapy during pregnancy, before, and after delivery. Conclusion: Second-generation insulin analogues and newer insulin infusion systems that automatically self-adjust according to patients continuous glucose monitor readings are important tools improving the treatment and quality of life of these women. Multi-institutional and disciplinary teams are working to develop and evaluate a pregnancy-specific artificial pancreas. Address for correspondence: Professor of Endocrinology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psycology, "Sapienza" University of Rome, via di Grottarossa, 1035, CAP 00189, Rome, Italy. E-mail: angela.napoli@uniroma1.it Grant from Medtronic to "Clinical and Molecular Department" of "Sapienza" University, Rome. The author has no conflicts of interest to declare. Clinical Trials Identifier: NCT03761615. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

08:55

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Sphingadienes show therapeutic efficacy in neuroblastoma in vitro and in vivo by targeting the AKT signaling pathway The authors would like to note an omission of disclosure in this paper. Author JDS is cofounder, equity-holder, and consultant of GILTRx Therapeutics. Correction to: Inhibitory effects of tea polyphenols by targeting cyclooxygenase-2 through regulation of nuclear factor kappa B, Akt and p53 in rat mammary tumors The authors regret to inform that there were unknowing errors in figures. The corrected images are given below. These figures are not affecting the results and conclusion of the manuscript. Hence, the text in original paper remains unchanged. Axitinib pharmacologic therapeutic monitoring reveals severe under-exposure despite titration in patients with metastatic renal cell carcinoma Summary Introduction New therapeutic strategies combining axitinib and immune checkpoint blockers are ongoing in metastatic renal cell carcinoma (mRCC). These strategies do not consider the pharmacokinetic variability of axitinib. We aimed to describe the risk of axitinib under-exposure using routine pharmacologic therapeutic monitoring (PTM). Methods We analyzed axitinib dosage in nine patients with mRCC. Routine axitinib concentration measurements were centralized at Henri Mondor University Hospital (Créteil, France) using a validated method. The primary objective was to describe the evolution of Cmax dosages (1 to 6 h after oral intake) during routine axitinib titration. Results Nine patients with available Cmax axitinib dosages were included. Four out of the nine patients had axitinib titration and Cmax dosages were performed before and after titration. All but one corrected their plasma axitinib exposure after titration, suggesting of a titration success. The last patient was monitored in the Henri Mondor Hospital routine PTM program and a pharmacokinetic profiling was performed after controlled oral intake. Results suggested a poor axitinib absorption. This patient experienced early tumor progression as best response. Conclusion We report a patient with significant axitinib under-exposure, possibly due to a poor absorption. PTM should be evaluated and considered in drug developments evaluating combination therapies based on axitinib. Delineation of proapoptotic signaling of anthracene-shelled M 2 L 4 metallacapsules and their synergistic activity with curcumin in cisplatin-sensitive and resistant tumor cell lines Summary Since the introduction of cisplatin into clinical practice a few decades ago, the topic of metal-based drugs has expanded significantly. Recent examples emphasize on metallosupramolecules as an emerging class of compounds with diverse properties. They can trigger unique cellular events in malignant cells or serve as molecular hosts for various biologically active compounds, including anticancer agents. The anthracene-shelled M2L4 coordination nanocapsules under research have already proved very high anticancer potency with remarkable selectivity and lack of cross-resistance. In this study, we provide an oncopharmacological evaluation of the Pt(II)- and Pd(II)-clipped M2L4 nanocapsules; we report a thorough analysis of their synergistic effects in combined treatments with the pleiotropic anticancer agent curcumin. We examined changes in cellular expression of several apoptosis-related proteins in a panel of tumor cell lines with different chemosensitivity towards cisplatin, i.e. HT-29, HL-60 and its resistant strains HL-60/CDDP and HL-60/Dox, in order to assess the molecular mechanisms of their antitumor activity The results of the immunoassay concluded activation of the mitochondrial apoptotic pathway in all the screened tumor lines. A prevalent modulation of the extrinsic apoptotic signaling cascade was observed in the chemoresistant variants. Curcumin interactions of the tested compounds were estimated against the cisplatin-refractory cell line HT-29 via the Chou-Talalay method (CTM), whereby the palladium species yielded superior synergistic activity as compared to their platinum analogues. Synergistic effect and reduced toxicity by intratumoral injection of cytarabine-loaded hyaluronic acid hydrogel conjugates combined with radiotherapy on lung cancer Summary The aim of this study was to explore the synergistic anti-tumor effects of cytarabine hyaluronic acid-tyramine (Ara-HA-Tyr) hydrogel conjugates and radiotherapy (RT) in the Lewis lung cancer (LLC) xenograft model, and the mechanisms involved. The radiotherapy sensitization ratio (SER) of 0.5 μg cytarabine (Ara-C) was 1.619 in the LLC cells. Ara-HA-Tyr was prepared by encapsulating Ara-C into hyaluronic acid-tyramine (HA-Tyr) conjugates. The hydrogels were formed through the oxidative coupling of tyramines by hydrogen peroxide (H2O2) and horseradish peroxidase (HRP). Mice engrafted with the LLC cells were given intra-tumoral injections of saline, Ara-C or Ara-HA-Tyr, with or without RT. The combination of Ara-HA-Tyr and RT increased survival compared to free Ara-C and RT (p < 0.05), and prolonged tumor growth delay (TGD). Furthermore, the RT + Ara-HA-Tyr combination therapy significantly reduced 18F-FDG uptake, induced cell cycle arrest at G2/M-phase, increased apoptosis and histone H2AX phosphorylation (γ-H2AX), and decreased the proliferation index (Ki67) in tumor cells compared to either monotherapy. Taken together, Ara-C encapsulated with HA-Tyr effectively sensitized tumor xenografts to RT and showed significantly less systemic toxicity. Graphical abstract In this work, Ara-C encapsulated with hyaluronic acid–tyramine conjugates (HA–Tyr) was prepared and used to investigate its synergistic anti-tumor efficacy by combination with radiotherapy in the Lewis lung cancer xenograft model. The synergistic mechanism may be related to tumor cell cycle redistribution, apoptosis and expression of histone H2AX phosphorylation. Clinical outcomes of advanced stage cancer patients treated with sequential immunotherapy in phase 1 clinical trials Summary Background Given the increasing number of available immunotherapeutic agents, more patients are presenting after failing immunotherapy in need of new treatment options. In this study, we investigated the clinical outcomes of patients treated with sequential immunotherapy. Methods We performed a retrospective review of 90 advanced stage cancer patients treated on immunotherapy-based phase 1 clinical trials at Winship Cancer Institute from 2009 to 2017. We included 49 patients with an immune checkpoint inhibitor (ICI)-indicated histology. Patients were analyzed based on whether they had received prior ICI. Clinical outcomes were overall survival (OS), progression-free survival (PFS), and clinical benefit (best response of complete response, partial response, or stable disease). Univariate analysis (UVA) and multivariate analysis (MVA) were performed using Cox proportional hazard or logistic regression model. Covariates included age, liver metastases, number of prior lines of therapy, histology, and Royal Marsden Hospital (RMH) risk group. Results The most common histologies were melanoma (61%) and lung/head and neck cancers (37%). More than half of patients (n = 27, 55%) received at least one ICI prior to trial enrollment: ten received anti-PD-1, two received anti-CTLA-4, five received anti-PD-1/CTLA-4 combination, and ten received multiple ICI. In MVA, ICI-naïve patients had significantly longer OS (HR: 0.22, CI: 0.07–0.70, p = 0.010) and trended towards higher chance of CB (HR: 2.52, CI: 0.49–12.97, p = 0.268). Patients who received prior ICI had substantially shorter median OS (10.9 vs 24.3 months, p = 0.046) and PFS (2.8 vs. 5.1 months, p = 0.380) than ICI-naïve patients per Kaplan-Meier estimation. Within the ICI-naïve group, 78% (7 of 9) of patients who received prior interleukin (IL-2) or interferon gamma (IFNγ) experienced disease control for at least 6 months, compared to a disease control rate of 15% (2 of 13) in patients who had received chemotherapy, targeted therapy, or no prior treatment. Conclusions ICI-naïve patients may experience improved clinical outcomes on immunotherapy-based phase 1 clinical trials than patients who have received prior ICI. This may be particularly true for patients who received prior IL-2 or IFNγ. Further development of immunotherapy combination therapies is needed to improve clinical outcomes of these patients. These results should be validated in a larger study. Increased DKC1 expression in glioma and its significance in tumor cell proliferation, migration and invasion Summary The dyskeratosis congenita 1 (DKC1) gene is located on the X chromosome at Xq28. Dyskerin encoded by the DKC1 gene is associated with the formation of certain small RNAs and the telomerase activity. Inherited mutations in DKC1 inactivate the dyskerin and causes dyskeratosis congenital, which is characterized by skin defects, hematopoiesis failure, and increased susceptibility to cancer. DKC1 reportedly up-regulates in several human cancers, including renal cell carcinoma and prostate cancer. Dyskerin is deregulated in B-chronic lymphocytic leukemia and breast carcinomas, but its expression and function in glioma have hardly been investigated. Hence, we were prompted to collect tissue samples and implement cell experiments. Our study reveals that DKC1 expression is significantly increased in the pathological tissues of glioma compared with that in normal tissues. The increased staining of DKC1 is related to the World Health Organization stages of tumors. DKC1 knockdown also significantly inhibits glioma cell growth by altering the expression of cell cycle-relative molecules to arrest at the G1 phase. In the transwell chamber, DKC1 knockdown glioma cells exhibit low motility. Consistent with classic oncogenic pathways, N-cadherin, HIF-1α, and MMP2 expression levels are lower compared with those of the control group. Therefore, DKC1 up-regulation in gliomas is common and necessary for extensive tumor growth. The phenotype of glioma cell lines after DKC1 down-regulation suggests its use as a valuable clinical treatment strategy. A high-throughput drug screen identifies auranofin as a potential sensitizer of cisplatin in small cell lung cancer Summary Small cell lung cancer (SCLC) is a highly lethal malignancy with the 5-year survival rate of less than 7%. Chemotherapy-resistance is a major challenge for SCLC treatment in clinic. In the study, we developed a high-throughput drug screen strategy to identify new drugs that can enhance the sensitivity of chemo-drug cisplatin in SCLC. This screen identified auranofin, a US Food and Drug Administration (FDA)-approved drug used therapeutically for rheumatoid arthritis, as a sensitizer of cisplatin. Further study validated that auranofin synergistically enhanced the anti-tumor activity of cisplatin in chemo-resistant SCLC cells, which was accompanied by the enhanced induction of cell cycle arrest and apoptosis. The synergistic action of auranofin and cisplatin was through ROS overproduction, thereby leading to mitochondrial dysfunction and DNA damage. Furthermore, in vivo study demonstrated that the combination treatment of auranofin and cisplatin dramatically inhibited tumor growth in SCLC. Therefore, our study provides a rational basis for further clinical study to test whether auranofin could enhance the sensitivity of cisplatin-based therapy in SCLC patients. LEF1-AS1 contributes to proliferation and invasion through regulating miR-544a/ FOXP1 axis in lung cancer Summary Long non-coding RNAs (lncRNAs) are increasingly recognized as important regulators in tumor development. This study aims to investigate the potential role oflncRNALEF1-AS1, in the progression of lung cancer. Quantitative real-time PCR (qRT-PCR) and western blot assays showed that LEF1-AS1 was upregulated while miR-544a was downregulated in lung cancer specimens and cells. Overexpression of LEF1-AS1 led to the enhancement of cell proliferation and invasion, revealed by CCK-8 assay and transwell assay. A negative correlation was found between LEF1-AS1 and miR-544a. BLAST analysis and dual-luciferase assay confirmed that FOXP1 is a downstream effector of miR-544a. Therefore, the LEF1-AS1/miR-544a/FOXP1 axis is an important contributor to lung cancer progression. Collectively, our novel data uncovers a new mechanism that governs tumor progression in lung cancer and provides new targets that may be used for disease monitoring and therapeutic intervention of lung cancer. Discovery and anticancer evaluation of a formononetin derivative against gastric cancer SGC7901 cells Summary Background Gastric cancer (GC) is the second most common cause of cancer-related death worldwide. Novel anticancer drugs against gastric cancer are urgently needed. Methods Compound 10 was designed and synthesized via a molecular hybridization strategy based on the natural product formononetin. It was evaluated for their antiproliferative activity against three gastric cancer cell lines (SGC7901, MKN45 and MGC803). Results Derivative 10 displayed potently antiproliferative activity with an IC50 value of 1.07 μM against SGC7901 cells. Derivative 10 could inhibit the growth and migration against gastric cancer SGC7901 cells through the Wnt/β-Catenin and AKT/mTOR pathways. From the in vivo expremints, it could effectively inhibited SGC7901 xenograft tumor growth in vivo without significant loss of the body weight. Conclusion Derivative 10 is an novel antitumor agent with potential for further clinical applications to treat gastric cancer. Graphical abstract

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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A Narrative Literature Review of the Identity Negotiation of Bilingual Students Who are Labelled ESL Abstract English as a second language or ESL instruction is said to be for students who have moved to the United States (or Canada) from another country and temporarily need assistance in learning the English language. However, statistically, a vast majority of ESL students in the United States were born in the US and are US citizens. When students are labelled as ESL and placed in this tract of alternative education, there is an othering process going on. This narrative literature review questions how do these ESL students negotiate their own identity. It is shown that ESL students are socialized into a deficit model, placed in classrooms where the discourse is hegemonic and are placed in location of constant power play where the system is set up against them. Correction to: Subject Advisers' Perception of Curriculum Delivery in the Intermediate Phase in South Africa In the original publication of the article, the authors' institution name was published incorrectly. The correct institution name is given in this Correction. What are the Qualities of Good Citizenship in Post-genocide Rwanda? High School Teachers Speak Through a Q-Methodological Approach Abstract Teachers play a crucial role in the political socialization of adolescents. Using Q-Methodology, we explored high school teachers' conceptions of good citizenship in post-genocide Rwanda. Teachers ranked 50 statements, describing a 'good citizen', on a 9-column grid, anchored by 'least important citizenship behaviour' and 'most important citizenship behaviour'. The four perspectives that emerged viewed good citizenship as (a) being mindful or considerate of the 1994 genocide perpetrated against the Tutsi and promoting unity as well as reconciliation among Rwandans; (b) being morally upright and demonstrating a strong sense of patriotism; (c) being politically enthusiastic; and (d) promoting justice. The study argues for a shift towards more critical forms of citizenship. It also advocates the reinforcement of democratic and participatory skills among teachers. The Data of Deviance: Disintegrative Shaming and Exclusion in Queensland Schools Abstract It is the purpose of this study to determine the extent to which the implementation of the Positive Behaviour for Learning (PBL) model and its focus on data-driven behaviour management has impacted on exclusion rates in Queensland public schools and, as such, the commitment of Queensland public schools to reintegration of students with behavioural issues. Using the open source data on student exclusion rates and the reasons for exclusion, it is possible to determine shifting patterns over the last 10 years. In doing so, it has been possible to identify how the approach to exclusion in Queensland public schools has changed in the period since the introduction of the OneSchool data aggregation software. An analysis of exclusion data shows that while long-term suspensions have decreased over the last 10 years, the rate of short-term suspension and exclusion has increased. There has been a particular increase in disciplinary absences related to conduct issues like refusal to participate in class, rather than more serious violations like physical violence or drug use. Using Braithwaite's reintegrative shaming model as a framework to analyse this behavioural exclusion data indicates that an over-reliance on exclusion is steering Queensland schools away from the principles of restorative justice, and has a negative impact on student outcomes. Implications of the Legalization of Marijuana in Canada Affecting Educational Policy Abstract This research attempts to explore the implications of Bill C-45: The Cannabis Act and how this could influence educational policy in schools. The researchers sought the perspectives of multiple stakeholders involved in education, specifically their views on mitigating the transition, and other topics such as attitudes towards policy change, drug testing, and the impacts on students and teachers. This research includes components of qualitative research, statistical analysis, and review of academic literature and policy. The qualitative research portion was undertaken through in-person interviews with three teachers, four principals, and a board of education trustee in a large city in Western Canada. The statistical analysis portion of the investigation was conducted through a survey distributed to a sample of 384 people of the general public over the age of 18. This article focuses on three of the five predominate themes found in the research: (i) sustainable approaches to educating stakeholders about cannabis following legalization, (ii) comparison of views for and against drug testing between educators and the general public, and (iii) the nature of consumption does matter. There will inevitably be countless implications to follow based upon this political shift in Canada that will directly and indirectly affect stakeholders in education. Findings addressing these perceived impacts and considerations can help educational professionals mitigate the possible negative consequences of Bill C-45. Disarming Privilege to Achieve Equitable School Communities: A Spiritually-Attuned School Leadership Response to Our Storied Lives Abstract This conceptual paper addresses the nature of white male privilege within school administration and how that privilege, through an examination and clarification of equity as justice, can be checked, interrogated and possibly moderated by a reflection on the spiritual nature of leading for democratic change. Conditioning Tendency Among Preschool and Primary School Children: Cross-Sectional Research Abstract The present study aims to understand children's behavior within classroom settings in terms of conditioning theories. It was designed based on grounded theory. Data were collected through participant observation and 98 children whose ages varied between 6 and 10 years were observed. Data were inductively analyzed. Findings indicated that kindergarteners and first graders tend toward classical conditioning and need more teacher control to adjust to classroom settings, whereas children aged from 9 to 10 years behave based on operant conditioning. It is proposed that differences in conditioning stem from teachers' classroom management strategies, and cognitive development. A Dialogue of Shared Discoveries on Immigration: A Duoethnography of International Students in Canada Abstract International students are believed to contribute significantly in education and research as they bring a rich variety of perspectives, experiences, and languages. International students are frequently categorized into one homogenous group; however, this categorization dishonours their complex intersectional diversity and background that provides cultural capital. There is a need to understand the many manifestations of the complex and intersectional diversity in the backgrounds of international students. These students have many different reasons to immigrate to developed countries and undertake a rigorous academic program, including pursuing high academic goals, gaining personal knowledge, developing research skills, and widening employment opportunities. Using a duoethnographic dialogical approach, this article focuses on the experiences of two female international PhD students, one from Nigeria and the other from Costa Rica as they embark on a journey of shared self-discoveries on their mobility to Canada. Our paper takes a broad perspective on the processes behind mobility coming from different cultures and nationalities that meet in Canada. Some of our findings include the impact of background when transitioning to a new country, the role of reflective dialogue when questioning the source of our cultural assumptions and ethical judgments. In addition, we find that duoethnography has a strong effect to re-story our own narratives and perspectives. Finally, this dialogue allows us to broaden how we come to understand and extract meaning from our experiences as international students. Second Language Reading from an Hegelian Perspective Abstract Second language research has traditionally been characterized by the cognitive perspective which focuses on how the individual processes language. There has been an emerging trend over the past few decades on taking into consideration the social influences on second language learning based on diverse theoretical frameworks. Research on second language reading is no exception. Hegel points out the unique features of publicity, persistence over time, resistance to negation, universality and objectivity of the written form. These features enable the written form to perform some social and collective functions such as cultural preservation and enforcement of contracts that cannot be replaced by the spoken form. Hegel's philosophy also suggests that reading in a second language is qualitatively different from reading in a first language, and second language reading is an enculturation process. Hegel's accounts on these three aspects of second language reading provide new insights to both theories and practice of the teaching of second language reading. Why on Earth Would Some People Reject Democracy? An Autoethnographic Reflection on Education and Democracy in Egypt Abstract In 2013, thousands of Egyptians protested in the streets of Cairo in an effort to overthrow the country's first democratically elected president only 1 year after he took office. Some of my acquaintances participated in those protests, chanting "we do not want democracy." Several observers tried to analyze and understand this strange phenomenon of declining democracy after many Egyptians had waited so many years for it. However, using an autoethnographic method, I argue that any analysis of this phenomenon that does not include curriculum and education is inadequate. This autoethnographic essay argues that Egypt's curriculum and its schooling system are fundamental factors that contributed to this phenomenon. Fundamentally, this paper discusses the theoretical and practical relationship between curriculum and democracy from an autoethnographic perspective by assessing the nature of this relationship both in democratic societies and in Egypt. Furthermore, an overview of the Egyptian educational system is provided to answer the basic question of this paper: why would some people reject democracy?

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Genetic analysis of resistance to bacterial leaf spot in the heirloom lettuce cultivar Reine des Glaces Abstract Bacterial leaf spot (BLS) is a disease that affects lettuce (Lactuca sativa L.) worldwide. The disease is caused by the bacterium Xanthomonas campestris pathovar vitians (Xcv), which exclusively infects lettuce and is particularly devastating in warm humid climates. Reine des Glaces (RG), an old Batavia-type cultivar, exhibited an uninvestigated partial resistance to Xcv. Quantitative trait loci (QTLs) were analyzed using two recombinant inbred line (RIL) populations derived from RG × Eruption and RG × Delsay using three isolates collected in California and Canada, each representing a different race, and an isolate collected in France. A major QTL was identified in linkage group 2 in both populations; additional, minor QTLs were also detected in other linkage groups. The major QTL collocates with the Xanthomonas resistance 1 (Xar1) and Xanthomonas campestris vitians resistance (Xcvr) genes that had previously been identified using RIL populations derived from Salinas 88 × La Brillante and PI 358001-1 × Tall Guzmaine. RG provides another resistance resource for combating BLS using data provided by this study for marker-assisted selection. Current understanding of genetic and molecular basis of cold tolerance in rice Abstract Rice (Oryza sativa L.) is one of the most important crops worldwide, but its growth and production can be severely affected by climate change. As a tropical species, rice is in general vulnerable to the adverse effects of low temperature. To cope with or adapt to cold stress condition, rice has evolved elaborate regulatory mechanisms under both natural and artificial selection. Over the past few decades, intensive research efforts have been focused on abiotic stress biology in rice with genetic, genomic, and molecular strategies, disclosing a series of potential genetic determinants and mechanisms controlling cold stress tolerance. Here, we review cold tolerance (CT)-related quantitative trait loci (QTLs) identified by linkage and association mapping, together with key genes involved in cold sensing, signaling, and response. More importantly, recent studies have shown that CT-related QTLs/genes can be employed in genomic breeding aiming at developing cold-tolerant rice. Overall, the recent research progresses in understanding the complex genetic and molecular mechanisms of CT provide a substantial basis for CT improvement in rice. Dissecting the genetic architecture of important traits that enhance wild germplasm resource usage in modern maize breeding Abstract Domestication and improvement of maize (Zea mays L.) from ~ 10,000 years ago has produced remarkable alterations from its wild ancestor, teosinte. To investigate the genetic basis of changes in plant and inflorescence traits, we developed a teosinte–maize intermated population. More than 200 common quantitative trait loci (QTLs) and 44 QTL clusters were identified underlying 13 vegetative and reproductive traits. Among them, few common QTLs with major effects were observed, which supported previous hypotheses that a small number of major loci can explain a large portion of phenotypic changes during domestication. Additionally, we found many moderate or minor QTLs that might have critical roles in shaping plant architecture and enhancing grain yield of modern maize. Although maize has better performance for the traits studied here, teosinte still harbored desirable alleles in some of the common QTLs. Furthermore, we integrated multiple datasets and predicted candidate genes underlying these QTLs. This study elucidates the genetic basis of these vegetative and reproductive traits in maize and teosinte, and suggests the possibility of improving maize by teosinte re-domestication using a small number of loci. Peptidomics-based study reveals that GAPEP1, a novel small peptide derived from pathogenesis-related (PR) protein of cotton, enhances fungal disease resistance Abstract Peptides play important roles in many important biological processes. For instance, plant antimicrobial peptides, which are essential components of innate immunity and exert rapid defense response, have a broad activity against pathogenic bacteria, fungi, enveloped viruses, and parasites. Verticillium wilt, caused by the soil-borne fungus Verticillium dahliae, is a destructive vascular disease in plants. In this study, we used mass spectrometry approach to detect and characterize important peptides, especially antimicrobial peptides from roots of Gossypium arboretum and to evaluate their inhibitory activities against phytopathogenic fungi. We have identified a novel small peptide, GAPEP1, which is derived from the N-terminal of Pathogenesis-related protein STH-2 protein and upregulated by V. dahliae inoculation. GAPEP1 is localized in the nucleus and cell membrane. Plants with exogenous treatment or overexpressing GAPEP1 both exhibited enhanced disease resistance as compared with the control group. Our results provide the cotton endogenous peptides library that could potentially be used to develop natural, targeted, and environmentally friendly strategies to enhance the resistance of Gossypium species against biotic attackers. Transcriptome analysis reveals genes commonly responding to multiple abiotic stresses in rapeseed Abstract Rapeseed production is limited by abiotic stresses such as drought, salinity, and low temperature. Evidences suggest that common stress response genes are shared by multiple stresses. To study how rapeseed responds to abiotic stresses at transcriptional level and identify genes that regulate multiple abiotic stress tolerance, we investigated transcriptional dynamics of the rapeseed treated by abscisic acid (ABA), salt, dehydration, and cold stresses at two different time points, respectively. A total of 30,908 differentially expressed genes (DEGs) under 4 abiotic stresses were identified. There were 2568 upregulated and 4376 downregulated DEGs (2-fold change) commonly shared by four stresses. Analysis of the DEGs identified significantly enriched gene ontology biological processes under multiple stress conditions. The commonly shared DEGs included 225 upregulated and 294 downregulated transcription factors belonging to 35 and 40 different families, respectively. The representative mostly upregulated and downregulated DEGs at each time point of abiotic stress treatment were presented. We identified a list of core abiotic stress genes commonly regulated by four stresses, which mainly included ERD15, RAB18, LEA14, and transcription factors belonging to ERF, bZIP, and MYBR1 families. The findings of shared abiotic stress responsive genes may help develop strategies for breeding rapeseed varieties with improved tolerance to multiple abiotic stresses. Basmati rice lines development carrying multiple bacterial blight resistance genes pyramided using the marker-assisted backcross breeding approach Abstract Basmati rice is treated as one of the world's best rice due to its extra-long grain and unique aroma,. Over the last decade, Pakistan has earned more than US$2 billion through basmati export. Unfortunately, basmati rice is being threatened with bacterial leaf blight (BLB) disease that leads to poor production and quality. We attempted pyramiding of BLB genes through marker-assisted backcross breeding using Super Basmati as the recipient and IRBB60 as the donor parent. BLB resistance genes Xa4, xa5, and Xa21 were used for introgression. Molecular markers MP1 and MP2, RM122, and pTA248 were used for Xa4, xa5, and Xa21 genes respectively for foreground selection. The 85 SSR polymorphic molecular markers were used for background selection, which showed a more than 90% recurrent parent genome recovery. Phenotypic traits for grain dimensions were also considered while selecting backcross female parents from BC1F1 to BC5F1, which resulted in saving the resources from background selection before the selfing of backcrossed lines. Multiple lines carrying BLB resistance genes combinations Xa4 + xa5 and Xa4 + xa5 + Xa21 were developed. The BC5F4 uniform lines showed resistance against BLB disease at hotspot locations. One of the developed lines, PKBB15–116, which has a yield advantage of more than 10%, tolerant to lodging, and has basmati quality. These pyramided lines in basmati background will also be helpful for breeders to incorporate resistance genes in a shorter period of time, in order to develop new basmati rice varieties in future. An update on molecular mechanism of disease resistance genes and their application for genetic improvement of rice Abstract Multiple pathogens cause rice various diseases affecting its yield and quality. Pyramiding resistance genes or quantitative traits loci into rice cultivars to enhance their resistance is an operable and optimal strategy for rice genetic improvement. New technologies and methods accelerate the identification and cloning of the resistance genes from landraces, domesticated and wild rice germplasm accessions. Some of these superior resistance genes have been successfully pyramided into diverse rice cultivars worldwide based on molecular marker-assisted selection. The underlying molecular mechanisms of some resistance genes have been uncovered which support their stacking into rice cultivars in a proper manner. The genetically improved rice lines show broad spectrum and durable resistance to different pathogens, which can greatly contribute to high yield and outstanding quality of rice cultivars. This paper summarizes the cloned major resistance genes, elucidates the underlying molecular mechanisms, and proposes the operable strategies to use these genes for rice genetic improvement. Genetic variation analysis of field isolates of clubroot and their responses to Brassica napus lines containing resistant genes CRb and PbBa8.1 and their combination in homozygous and heterozygous state Abstract Brassica napus is one of the most important oilseed crops in the world and Plasmodiophora brassicae is a serious threat causing yield reduction. CRb and PbBa8.1 resistance genes are known to be highly effective against P. brassicae race 4. Here, we combined two clubroot resistance (CR) genes through marker-assisted selection (MAS) and developed CR homozygous lines. The CR parental and pyramided lines were crossed with genetically male sterile (GMS) plants to generate heterozygous lines. In order to confirm their differences on resistance, the parental and generated lines were inoculated with 9 P. brassicae field isolates in the greenhouse and resistant test also evaluated in different naturally infested fields. The CR pyramiding lines exhibited high levels of resistance to the most isolates than line containing any single resistance gene; comparatively, the homozygous lines demonstrated a higher resistance than the heterozygous. The genetic variation among P. brassicae isolates was analyzed through simple sequence repeat (SSR) marker and significant divergences were recorded among the 9 tested field isolates and the result was consistent with data acquired from the greenhouse and natural field experiments. This study will certainly provide a novel molecular strategy for the breeding of the durable CR B. napus varieties in future breeding programs. Multi-environments and multi-models association mapping identified candidate genes of lint percentage and seed index in Gossypium hirsutum L. Abstract Upland cotton (Gossypium hirsutum L.) accounts most of the natural fiber production worldwide. Lint percentage (LP) and seed index (SI) are important components of cotton fiber yield, which is a constant breeding goal of cotton. So, the loci underpinning LP and SI should be extensively dissected. Here, one single-locus and four multi-locus genome-wide association study (GWAS) models were employed to detect candidate loci for lint percentage and seed index under seven environments with 196 upland cotton accessions and 41,815 single nucleotide polymorphism (SNP) markers. Totally, 39 and 45 significant quantitative trait locus (QTL) were identified in at least two environments or two models, including 24 previously reported QTLs and six pleiotropic QTLs. Referred to the genome and gene expression database of TM-1, 614 candidate genes were detected for lint percentage and seed index, including 103 genes preferentially expressed in fiber or ovule. The gene Gh_A10G0378, functioned in potassium ion transport, was considered to be related to lint percentage. Collectively, the associated markers and promising genes detected herein will help to elucidate the genetic architecture of lint percentage and facilitate fiber yield improvement in cotton. Genome-wide association analysis in tetraploid potato reveals four QTLs for protein content Abstract Valorisation of tuber protein is relevant for the potato starch industry to create added-value and reduce impact on the environment. Hence, protein content has emerged as a key quality trait for innovative potato breeders. In this study, we estimated trait heritability, explored the relationship between protein content and tuber under-water weight (UWW), inferred haplotypes underlying quantitative trait loci (QTLs) and pinpointed candidate genes. We used a panel of varieties (N = 277) that was genotyped using the SolSTW 20 K Infinium single-nucleotide polymorphism (SNP) marker array. Protein content data were collected from multiple environments and years. Our genome-wide association study (GWAS) identified QTLs on chromosomes 3, 5, 7 and 12. Alleles of StCDF1 (maturity) were associated with QTLs found on chromosome 5. The QTLs on chromosomes 7 and 12 are presented here for the first time, whereas those on chromosomes 3 and 5 co-localized with loci reported in earlier studies. The candidate genes underlying the QTLs proposed here are relevant for functional studies. This study provides resources for genomics-enabled breeding for protein content in potato.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

08:54

Who Burns out More? Comparison of Burnout Levels Between Teachers and Physicians in the Czech Republic Abstract Despite burnout being considered primarily a syndrome related to medical professionals, it is now known that it affects a wider range of professions as well. It is seen as a state of complete physical, emotional, and cognitive depletion. In physicians, not only can burnout lead to work-related absenteeism but also it may affect their patients while teachers' burnout may affect the mental well-being of their students. This study explored whether teachers have higher or comparable rates of burnout with the burnout rates of physicians. Furthermore, we compared them to the norms we established in the Czech Republic in the previous year. Cross-sectional data collection was utilized through a combination of multiple questionnaires. The questionnaires analyzed for the purpose of this study were the SMBM and BDI-II. Regardless of gender, physicians suffer from significantly higher burnout symptomatology when compared with teachers. These differences were found to be statistically significant. Furthermore, significant differences were also found between males with depressive symptomatology. We did not observe this difference in females. Our results suggest that, although burnout is a syndrome that appears regardless of profession, its manifestation can be quite different depending on the type of job. Overall, higher levels of burnout were found among female teachers compared with their male counterparts; between physicians, the situation was reversed; burnout affected more males than females. In all categories, more females were within the norm of Czech population. Nonetheless, the risk of burnout should not be underestimated in either of these professions. Chalmers' Principle of Organizational Invariance Makes Consciousness Fundamental but Meaningless Spectator of Its Own Drama Abstract The principles of classical physics, including deterministic dynamics and observability of physical states, are incompatible with the existence of unobservable conscious minds that possess free will. Attempts to directly accommodate consciousness in a classical world lead to philosophical paradoxes such as causally ineffective consciousness and possibility of alternate worlds in which functional brain isomorphs behave identically but lack conscious experiences. Here, we show that because Chalmers' principle of organizational invariance is based on a deficient nineteenth century classical physics, it is inherently flawed and implies evolutionary inexplicable epiphenomenal consciousness. Consequently, if consciousness is a fundamental ingredient of physical reality, no psychophysical laws such as Chalmers' principle of organizational invariance are needed to establish correspondence between conscious experiences and brain function. Quantum mechanics is the most successful and only modern physical theory capable of naturally accommodating consciousness without violation of physical laws. Twin Loss in the Uterus: Neurodevelopmental Impairment and Reduced Resilience? Abstract Spontaneous loss of a twin most often occurs in the first trimester. This phenomenon is called vanishing twin. Foetuses are especially vulnerable to various stress-related factors. As a result, twin loss in the uterus can produce deep and long-lasting consequences on mental health and may increase the risk of a variety of disease states in the surviving twin. In addition, twin loss may generate strong non-conscious stress that creates epigenetic alterations that impair the brain's development endocrine and inflammatory substances produced by perturbed signalling pathways. These altered signalling pathways may generate lasting dysfunctions in various areas of the limbic system, predisposing the surviving twin to psychological and emotional problems later in life. We also hypothesise that specific cfDNA and other substances from the dead twin during its reabsorption may affect the surviving twin's neurodevelopmental and emotional (e.g. resilience) development. 5-Methoxy- N,N -dimethyltryptamine: An Ego-Dissolving Endogenous Neurochemical Catalyst of Creativity Abstract 5-Methoxy-N,N-dimethyltryptamine (acronymized as 5-MeO-DMT) is sui generis among the numerous naturally occurring psychoactive substances due to its unparalleled ego-dissolving effects which can culminate in a state of nondual consciousness that is phenomenologically similar to transformative peak experiences described in various ancient contemplative traditions (e.g., Advaita Vedānta, Mahāyāna Buddhism, inter alia). The enigmatic molecule is endogenous to the human brain and has profound psychological effects which are hitherto only very poorly understood due to the absence of scientifically controlled human experimental trials. Its exact neuronal receptor binding profile is a matter of ongoing research; however, empirical evidence indicates that its remarkable psychoactivity is partially mediated via agonism of the 5-HT1A/2A (serotonin) receptor subtypes. Anthropological/ethnopharmacological evidence indicates that various cultures utilized 5-MeO-DMT containing plants for medicinal, psychological, and spiritual purposes for millennia. We propose that this naturally occurring serotonergic compound could be fruitfully utilized as a neurochemical research tool with the potential to significantly advance our understanding of the psychological and neuronal processes which underpin cognition and creativity (e.g., downregulation of the default mode network, increased global functional connectivity, neuroplasticity, σ1 receptor interactions, etc.). An eclectic interdisciplinary perspective is adopted, and we present converging evidence from a plurality of sources in support of our conjecture. Specifically, we argue that 5-MeO-DMT has significant neuropsychopharmacological potential due to its incommensurable capacity to completely disintegrate self-referential cognitive/neuronal processes (viz., ego death). The importance of unbiased systematic scientific research on naturally occurring endogenous psychoactive compounds is discussed from a Jamesian radical empiricism perspective, and potential scenarios of abuse are addressed, particularly in the context of neuroethics, cybernetic manipulation, and military research on torture. Assessment of Theory of Mind in Adults: Beyond False Belief Tasks Abstract Theory of Mind, or the ability to attribute mental states to the self and others, forms the foundation of social cognitive processes or social cognition. Since its conception in 1978, the construct has been enjoying increasing attention from researchers and it has been widely studied in the context of autism spectrum disorder. This paper tries to review the issues surrounding the assessment of the construct. Theory of Mind (ToM) assessment goes almost synonymously with false belief tests. And assessing ToM with false belief tasks did not pose a problem because the construct had traditionally been studied mostly, if not exclusively on children. This paper discusses the danger of testing theory of mind with false belief tasks only and the serious necessity to study the construct in the adult population. The paper also discusses why the construct needs to be assessed in a culture-specific manner, the problems with the existing recent tools that have been developed to measure the construct, the complexity of simulating real social stimuli, and the subtleties around the construct that is to be taken care of while developing assessment measures. Isomorphism: Abstract and Concrete Representations Abstract Looking at concrete representations of mathematical problems from an isomorphic perspective, this article suggests that every concrete representation of a mathematical concept is understood by reference to an underlying abstract representation in the mind of the comprehender. The complex form of every abstract representation of a problem is created by the gradual development of its elementary form. Throughout the process of cognitive development, new features are added to the elementary form of abstract representation, which leads to gradual formation of a fully developed abstract representation in the mind. Every developed abstract representation of a problem is the underlying source for understanding an infinite number of concrete isomorphic representations. Deep or abstract representations of a problem are shared by the concrete realizations or concrete forms of that problem. In other words, concrete representations of a problem are the realizations of a single abstract representation. This discussion is extended to mind-brain relationship and the possible isomorphism that could exist between mind and brain. The Dorsolateral Prefrontal Cortex, the Apathetic Syndrome, and Free Will Abstract The prefrontal cortex is deputed to higher functions, such as behavior and personality. It includes three regions: ventromedial, orbitofrontal, and dorsolateral. Each of them has a function. Devising, programming, and planning are all conditions related to the dorsolateral cortex, also responsible for rational content and decision. Damage to this region results in apathetic syndrome, a condition that causes loss of interest, initiative, and attention, and in the most severe cases leads to a lethargic state. It is also known as a form of secondary depression, the so-called pseudo-depression syndrome, according to Karl Kleist or apathetic-abulic-akinetic syndrome, according to Alexander Luria. The prefrontal dorsolateral syndrome is responsible for the reduction or abolition of free will. Free will is an expression of individual freedom. It allows the human being to have and express own opinions as well as to respect those of others. Free will is related to moral sense, a binomial which directs the individual towards a proper social conduct. In this review, we describe the effects of the pseudo-depression syndrome on free will, of which we treat both the anatomical site and the social aspect. ADHD and Time Perception: Findings and Treatments Abstract This mini review aims to explore the intricate connection between ADHD and time perception along with some new findings on new treatments to manage ADHD symptoms. The topic of time perception is addressed from a variety of perspectives and with an understanding that although differences in time perception are not listed among the primary symptoms of the disorder, they are of the utmost importance to understand the condition and possibly new treatment plans. We also review some of the new findings on ADHD and time perception, and look at the usefulness of certain psychometric tools like the Zimbardo Time Perspective Inventory recent research into educational video games and apps for managing the disorder. Analysis of Differential Expression of Neurotransmitter Receptors with TNF-a Treatment in Rat Primary Hypothalamic Cell Abstract In this study, tumor necrosis factor-alpha (TNF-α) was incubated to primary hypothalamic cell culture of rat as an important inflammatory cytokine and the effect of TNF-α to neurotransmitter receptors of the hypothalamus in vitro by real-time fluorescence quantitative PCR with PCR array for researching the effect of TNF-α to neuroendocrine system was analyzed. The result showed that the expression level of Avpr1a, Gabrr1, Grin1, Htr4, and Tspo 5 genes was obviously up and the other Adrb2, Cckbr, Chrm5, Chrna6, Gabra5, Gabra6, Grm8, Htr2c, Htr3a, Sstr1, and Tacr1 11 genes were down. Especially, Grin1 and Tacr1 were affected obviously, increased 3.12 and decreased 2.76, respectively. So, TNF-α can modulate the expression of many receptors of neurotransmitters of the hypothalamus by the special cell signal transduction pathways and alter the responsibility and exciting of these neurons to neurotransmitters corresponding. Furthermore, these changes can affect many hormone secretion of the hypothalamus and affect neuroendocrine function of rat. On Minds that Interpret Quantum Mechanics: a Tribute to Henry Stapp Abstract This essay describes what an anthropologist has learned from his ethnographic research with physicists who are engaged in quantum physics interpretation, including Henry Stapp. I argue that meta-physical considerations about "mind" among physicists often obscure the possibility of empirical research on concrete and individual minds and the role they play in quantum interpretation. Therefore, the philosophical rigor of quantum interpretation could benefit if individual interpreters could find an interest in discovering a manner of analyzing their own style of interpretation such that their own style would be communicable with others as a topic of conversation, rather than simply repeated dogmatically and argumentatively. Such considerations would require greater empirical attention to human thought itself, such that "mind" becomes less abstract and mystified, and thus more knowable and self-conscious.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

08:53

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

08:53

Associations Between Depression Literacy and Help-Seeking Behavior for Mental Health Services Among High School Students Abstract Despite the growth in school-based mental health services (SBMHS), rates of mental health help-seeking among adolescents remain low, especially for ethnic minority youth. This study examined factors associated with adolescents' help-seeking of mental health services among a sample of 369 racially diverse high school students (age M = 15.5 years, SD = 0.72, 81.3% were ethnic minorities). We examined the relationships among mental health literacy for depression, knowledge barriers related to services and providers, perceived stigmatization by others, emotional/behavioral difficulties, and actual help-seeking behavior. Logistic regression results showed that adolescents with higher mental health literacy for depression and more emotional/behavioral difficulties are more likely to report seeking help in general and from providers outside of school specifically, but not for services inside of school alone. Asian-American students were less likely to seek help than Caucasian peers. It is important to promote mental health literacy to encourage help-seeking among high school students. Leveraging Technology to Facilitate Teachers' Use of a Targeted Classroom Intervention: Evaluation of the Daily Report Card.Online (DRC.O) System Abstract Historically, teachers' uptake and implementation of empirically supported classroom interventions have involved substantial face-to-face consultation. However, most schools do not have the resources to provide this intensive level of support and many teachers may not need it. Thus, evaluation of alternative supports is warranted. In this pilot study, we evaluated the feasibility and effectiveness of an interactive web-based technology [i.e., the Daily Report Card.Online (DRC.O)] designed to facilitate teachers' use of the DRC with minimal external support and examined individual teacher characteristics associated with DRC use. Elementary school teachers (N = 54) were given access to the DRC.O Web site and asked to use it to implement a DRC with one child. With regard to implementation, 16% were short-term adopters (less than 1 month) and 39% were long-term adopters (1–7 months of use). On average, short-term adopters adhered to 37% of data entry procedures, whereas long-term adopters adhered to 74% of data entry procedures. Higher teacher stress was associated with shorter use and lower adherence. Web site analytics revealed that, on average, long-term adopters completed all steps of DRC development in less than 1 h and spent only 3 min per day engaged in data entry for progress monitoring. The magnitude of change in student target behaviors and Strengths and Difficulties Questionnaire scores was moderate to large. These results reveal the feasibility and promise of the DRC.O and generate hypotheses for future research. Implications for additional evaluation of technology-driven implementation supports for teachers are discussed. Effectiveness Trial of Brief Indicated Cognitive-Behavioral Group Depression Prevention in French-Canadian Secondary Schools Abstract Most adolescent depression prevention programs have been tested in the USA and other Anglo-Saxon countries. Their effects in other contexts are less clear. We conducted a pilot trial aimed at testing the effectiveness of the Blues program, a brief indicated cognitive-behavioral (CB) group program to prevent depression originally developed in the USA, in French-Canadian secondary schools. CB group facilitators were endogenous school clinicians. A total of 74 students (mean age= 15.50; 66% female) with elevated depressive symptoms were randomized to CB group (n = 37) or educational brochure control (n = 37). Participants completed diagnostic interviews and surveys at pretest, posttest, and 6-month follow-up. Results showed that CB group had a large, statistically significant effect on MDD onset at 6-month follow-up. CB group also had a positive effect on depressive symptoms, intermediate outcomes (pleasant activities, negative thoughts), and one secondary outcome (improved interaction with parents) at posttest. These effects were not maintained at follow-up. This trial replicates results from a previous US effectiveness trial. The clinically meaningful effects of brief indicated CB group prevention, at least with regard to the prevention of MDD onset, hold in French-Canadian students when the intervention is implemented by school clinicians. Work is still needed to augment and maintain CB effects in real-world practice. "Lost in Transition": A Systematic Mixed Studies Review of Problems and Needs Associated with School Reintegration After Psychiatric Hospitalization Abstract The purpose of this review was to identify the problems and needs associated with school reintegration after psychiatric hospitalization. Principles outlined by the Evidence for Policy and Practice Information and Coordinating Centre (EPPI-Centre) for systematic mixed studies reviews were used to search 14 electronic databases with all possible literature from inception to September 2017. Quality was appraised by two sets of two independent reviewers using an adapted version of the Mixed Methods Appraisal Tool. Fourteen studies met the inclusion criteria. The key themes revolve around the different systems of the bioecological model: the youth ontosystem, microsystems (family, school) and mesosystems (family–hospital, family–school, school–hospital). Predominant emergent themes of each system converged toward a better communication, collaboration and coordination among all concerned actors. Many problems seem to alter school reintegration after psychiatric hospitalization and different needs are still required to be met. Future research directions and implications for intervention are discussed. Loneliness and Personality Profiles Involved in Bullying Victimization and Aggressive Behavior Abstract Bullying is a worrisome reality due to its harmful consequences. Although many constructs have been associated with bullying victimization and aggressive behavior, its relationship both with loneliness and personality has received little attention. The main objective of this study is to identify differences in bullying victimization and aggressive behavior scores based on a typology of personality and loneliness profiles. Six hundred and four middle school students (54% female) from the province of León (Spain), aged between 12 and 15 (Mage = 13.3 ± 1.12), completed the Eysenck Junior Personality Inventory, the Loneliness Scales, the Bullying Victimization Scale, and the Short Aggression Questionnaire. Correlations, linear regressions, and latent profile analysis (LPA) were performed. Age (β = − 0.90, p < 0.001), peer loneliness (β = 0.70, p < 0.001), isolation (β = 0.18, p < 0.001), neuroticism (β = 0.06, p = 0.048), and psychoticism (β = 0.06, p = 0.026) predicted bullying victimization. Moreover, the LPA distinguished five distinct profiles based on the loneliness and personality subscales. The disruptive and peer-alienated profiles obtained the highest scores in bullying victimization, and the former also had the highest aggression scores. Loneliness and personality are closely linked to victimization and aggressive behavior. It is crucial for health and school communities to identify and address these vulnerabilities for the prevention of bullying victimization and aggression. Multi-tiered Approaches to Trauma-Informed Care in Schools: A Systematic Review Abstract Childhood trauma can adversely impact academic performance, classroom behaviour, and student relationships. Research has gradually explored integrated approaches to care for traumatised students in schools. Increasingly, research has pointed to implementation of multi-tiered programs to trauma-informed care for traumatised students in schools. However, evaluations of these programs are limited and no systematic review of the existing evidence has been conducted. The aim of this research was to be the first systematic review to explore evidence on multi-tiered, trauma-informed approaches to address trauma in schools. Results of this systematic review yielded 13 published and unpublished studies. Findings indicated that further research, guided by empirical evidence of the effectiveness of multi-tiered and trauma-sensitive approaches in schools, is required. Recommendations for research in the area of trauma-sensitive, multi-tiered care in schools are provided. Benefits of a Highly Entitative Class for Adolescents' Psychological Well-Being in School Abstract Previous studies of the protective factors for adolescents' psychological well-being in school have focused on the emotional relationships under the classroom climate. In contrast, the present study focused on the structural relationships among students. To investigate this issue, we examined the effects of class entitativity, that is, the extent that a class is a coherent group rather than a number of students, on students' attitudes about themselves, their peers, and the whole class. A total of 408 adolescents completed measures of perceived class entitativity (i.e., homogeneity and interaction among students), self-efficacy, peer trust, and identification with the class. The results of a structural equation model analysis indicated that class entitativity was positively correlated with students' self-efficacy and their identification with the class, which were in turn correlated with students' trust of their peers. Further analysis revealed that homogeneity was positively associated with students' self-efficacy, while higher level of interaction was associated with stronger identification with the class. These findings highlight the essential role of structural relationships between students in their psychological well-being and have implications for student-oriented practices in schools. Efficacy of a Combined Approach to Tier 2 Social-Emotional and Behavioral Intervention and the Moderating Effects of Function Abstract Systematic literature reviews have supported the effectiveness of behavioral Tier 2 interventions, with research being particularly plentiful in relation to Check-In/Check-Out (CICO) and social skills training (SST). Though findings indicate either approach is effective in isolation, a recent study suggested these approaches might be particularly effective when integrated. The purpose of the current study was to build upon this initial single-case design study with a larger sample within a randomized controlled trial. Participants included 91 elementary students who had been identified as being at risk of social-emotional and behavioral difficulties. Students were randomized into three intervention conditions: CICO only, SST only, and CICO + SST. Prior to intervention, information was collected regarding the function of student problem behavior and the extent of social skill deficits. Systematic direct observation data were then completed at pre- and post-test regarding student positive and negative social engagement. Multivariate general linear models were then conducted, with pre-test scores serving as covariates and intervention group and behavioral function serving as fixed factors. Results indicated that implementation of CICO, SST, and a combined CICO + SST was functionally related to a reduction in negative social engagement. Follow-up post hoc tests indicated that after adjusting for pre-test responding, the difference between conditions in effectiveness was moderated by behavioral function. Specifically, SST was less effective for students whose behavior functioned to escape social and academic situations. No such differences were noted between students whose behavior functioned to attain adult or peer attention. Implications for practice, methodological limitations, and directions for future research are reviewed. Child Maltreatment Knowledge and Responses Among Teachers: A Training Needs Assessment Abstract Knowledge gaps, false beliefs, and limited skills with regard to child maltreatment are commonly found among teachers, despite their vital role in the lives of maltreated children. In Canada, little has been done to develop training or other supports for teachers around detecting and responding to child maltreatment. This study conducted a multi-informant assessment of teachers' child maltreatment training needs, as well as identified factors that may influence teachers' training participation and use of maltreatment-related knowledge and skills. We gathered qualitative information from three informant groups in one Canadian city, namely 19 school social workers, 9 child welfare practitioners, and 21 foster caregivers. Participants shared their experiences when working with teachers to support maltreated children, as well as their beliefs about gaps in teachers' maltreatment-related knowledge and skills. Participants were also asked about factors that might influence the delivery of child maltreatment training to teachers and teachers' responses to maltreatment-related behaviour at school. Findings showed consensus across all three participant groups that child maltreatment training for teachers is currently inadequate. Participants identified gaps in knowledge and skills among teachers in the detection and reporting of suspected maltreatment, as well as in their use of trauma-sensitive classroom strategies. Findings also highlighted multi-level factors that may affect teachers' decision-making and actions in response to child maltreatment, especially school- (e.g. inadequate educational resources) and teacher-level influences (e.g. teacher overburden). Recommendations for teacher training, implications for school staff and other professionals, and future directions for research are discussed. How Do Parent Psychopathology and Family Income Impact Treatment Gains in a School-Based Intervention for Trauma? Abstract The current study examined the impacts of parent psychopathology and family socioeconomic status on symptom reduction for children participating in Bounce Back, a school-based intervention for elementary students exposed to trauma. Participants in this study were 52 first through fourth graders (Mage= 7.76; 65% male) who were predominately Latinx (82%). Schools were randomly assigned to immediate treatment or waitlist control. Children whose parents reported higher socioeconomic status showed steeper declines in symptoms compared to lower socioeconomic status. Further, children of parents who endorsed high PTSD symptoms reported attenuated treatment effects, whereas children of parents who endorsed high hostility reported enhanced treatment effects. Although Bounce Back is an effective intervention for reducing PTSD symptoms and improving coping skills among children exposed to trauma and other ongoing stressors, treatment gains are attenuated for children from families with low socioeconomic status, and parent psychopathology also impacts treatment effects. The effectiveness of Bounce Back may vary based on socioeconomic status and parent psychopathology. Future research should examine methods of tailoring Bounce Back for children coping with economic stress and parent psychopathology.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

08:52

Frau Univ. Lekt. DDr. Irmgard Simma mit dem Professorentitel ausgezeichnet DGfAN Ärzte für Akupunktur Nachruf auf Medizinalrat Dr. Gerhart Feucht Chinesische Ernährungstherapie bei Fluor vaginalis Vergessen wir die Männer nicht 15. Festspielgespräche zur Ganzheitsmedizin DÄGfA Editorial Qigongtherapie in der Frauenheilkunde

Frau Univ. Lekt. DDr. Irmgard Simma mit dem Professorentitel ausgezeichnetDGfANÄrzte für AkupunkturNachruf auf Medizinalrat Dr. Gerhart FeuchtChinesische Ernährungstherapie bei Fluor vaginalisVergessen wir die Männer nicht15. Festspielgespräche zur GanzheitsmedizinDÄGfAEditorialQigongtherapie in der Frauenheilkunde

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Religious Attendance and the Social Support Trajectories of Older Mexican Americans Abstract In this paper, we directly assessed the extent to which the association between religious attendance and the social support trajectories of older Mexican Americans is due to selection (spurious) processes related to personality, health status, and health behavior. We employed seven waves of data from the Hispanic Established Populations for the Epidemiologic Study of the Elderly (1993–2010) to examine the association between religious attendance and perceived social support trajectories (n = 2479). We used growth mixture modeling to estimate latent classes of social support trajectories and multivariate multinomial logistic regression models to predict membership in the social support trajectory classes. Growth mixture estimates revealed three classes of social support trajectories: high, moderate, and low. Multinomial logistic regression estimates showed that the odds of membership in the low support trajectory class (versus the high social support trajectory class) were lower for respondents who attended religious services yearly, monthly, weekly, and more than weekly than for respondents who never attend religious services. Religious attendance could not distinguish between membership in the moderate and high support trajectory classes. These results persisted with adjustments for age, gender, immigrant status, language proficiency, education, income, religious affiliation, marital status, living arrangements, contact with family/friends, secular group memberships, self-esteem, smoking, heavy drinking, depression, cognitive functioning, and physical mobility. We conclude that the association between religious attendance and the social support trajectories of older Mexican Americans is primarily driven by processes related to social integration, not selection. Do Income Supplemental Programs for Older Adults' Help Reduce Primary Caregiver Burden? Evidence from Mexico Abstract In countries such as Mexico without formal public long-term care policies, informal care becomes the main source of support for older adults. Alternative social programs, such as supplemental income programs, for older adults could alleviate caregiver burden, especially if supplemental income were to be used for paid care or to compensate non-paid family caregivers. This work is the first to analyze the effects of a supplemental income program for older adults on primary caregiver burden. To identify how such a program might affect caregiver burden, we analyze rich panel data on 433 adults 70 years and older in two communities, one receiving a supplemental income program and the other not, in Yucatan, Mexico. Data were collected in 2008 and 2009 among treatment and control groups before and 6 months after program introduction. We employ a difference-in-differences approach. In our sample, most care is provided by non-paid female caregivers. We find that individuals in both the treatment and control groups received fewer hours of care over time. The decrease was lower for older adults who received the supplemental income, but the difference with those who did not was not statistically significant. We also observe few changes on caregiving burden; even after program introduction, more than 98% of caregivers remained unpaid and the same primary caregiver remained. Altogether, our work suggests supplemental income programs have negligible effects on caregiving, making evident the urgent need for other strategies to support non-paid caregivers who bear most of the burden for old-age care in Mexico. Characteristics and Consequences of Family Support in Latino Dementia Care Abstract The purpose of this study is to explore variations in family support for Latino dementia caregivers and describe the role of the family in dementia caregiver stress processes. Content analysis is utilized with themes derived inductively from 16 in-depth interviews with Latino caregivers recruited in California from 2002 to 2004. Three types of family support are described: extensive (instrumental and emotional support from family, n = 3), limited (instrumental support from one family member, n = 7), and lacking (no support from family, n = 6). Most caregivers report limited support, high risk for burnout and distress, and that dementia-related neuropsychiatric symptoms are obstacles to family unity. Caregivers with extensive support report a larger family size, adaptable family members, help outside of the family, and formalized processes for spreading caregiving duties across multiple persons. Culturally competent interventions should take into consideration diversity in Latino dementia care by (a) providing psychoeducation on problem solving and communication skills to multiple family members, particularly with respect to the nature of dementia and neuropsychiatric symptoms, and by (b) assisting caregivers in managing family tensions — including, when appropriate, employing tactics to mobilize family support. Community Gerontology Model for Healthy Aging Developed in Mexico Framed in Resilience and Generativity Abstract Background: The aims of this paper are to present the evolutionary development of the Community Model of Healthy Aging (CMHA) and to show the main results of the community gerontology studies framed in each of the stages of the CMHA. Method: The study employs a qualitative community-based participatory research approach. We also measured several biochemical parameters, social support networks, and indicators of physical and cognitive functioning. Results: We identified three stages in the development of the CMHA. The first stage was informative (CMHA-I, 1994-2000) with more than 70% of the older adults participating in self-care programs for health. The second stage was formative (CMHA-F, 2001-2015) with more than 80% of older adults participating in self-care, mutual aid, and self-management programs. The third stage was emancipatory (CMHA-E, 2016-2018). In this last stage, we added resilience and generativity as basic elements to strengthen and enhance human capacities during aging, and more than 90% of older adults made optimal use of social support networks as a key strategy. Conclusion: Our findings suggest that the addition of resilience and generativity in the CMHA contributed to the active participation of older adults in the maintenance of functioning and the prevention and control of diseases linked to aging. Overcoming a Bad Day: a Qualitative Look into the Dementia Caregiving Experiences of Mexican-Origin Women in East Los Angeles Abstract The number of Latinos with Alzheimer's disease (AD) is projected to more than double by 2030. Yet, the current literature is lagging on Alzheimer's caregiving among Latinos. This study explores how Mexican origin women experience dementia caregiving, and the coping strategies they use to manage their caregiving situations. Nine women were identified as caregivers of a family member with AD or dementia from a larger study on caregiving. Interviews with them were collected and subsequently analyzed using a modified grounded theory approach to reduce the data to identify thematic content. All but one participant described caregiving as "tiring," "wearing," or "hard." They reported suffering from stress, insomnia, nervousness, migraines, and/or depression because of their caregiving experiences. Participants engaged in various coping strategies to help combat the perceived negative consequences of their caregiving experiences. The most commonly reported strategies were various forms of distraction, and meditation or prayer. The Mexican origin women in this study experience faced two types of interpersonal challenges related to dementia caregiving: changes in the care receiver's personality and behaviors, and physical care needs. They engaged in various coping to strategies to address the difficulties of their situation. This study provides formative research for identifying research questions and topics of examination in the future. Aging and the Hidden Costs of Going Home to Mexico Abstract Data from the Mexican Census reveal that between 2005 and 2015, nearly two million migrants returned voluntarily to Mexico from the United States. Currently, high rates of voluntary-return migration to Mexico continue at the same time that migration flows to the U.S. steadily decline. This return migration trend presents serious challenges for Mexico, a country that has long struggled to satisfy the health care demands of its population. However, little is known about return migrants' health care needs. In this study, we examine the health risk profiles and healthcare utilization for Mexican return migrants and the non-migrant population. We examine how these outcomes are affected by both the migration and return migration experience of the returnee population, while paying close attention to age-group differences. We employ inverse probability weighting regression adjustment (IPWRA) and logistic regression analysis of a sample of 348,450 respondents from the 2014 National Survey of Demographic Dynamics (ENADID) to test for differences in health conditions between those Mexican return migrants and non-migrants. We then turn to the Survey of Migration at Mexico's Northern Border (EMIF Norte, for its Spanish acronym) for the 2014–2017 period to further assess whether certain characteristics linked to aging and the migration experience influence the prevalence of chronic health conditions, and health insurance coverage among 17,258 returned migrants. Findings reveal that compared to non-migrants, returnees are more likely to be physically impaired. These poor health outcomes are influenced by the migration and return migration experience and vary by age group and duration of residence, the time that has elapsed since returning to Mexico. We do not find an association between return migration and mental or emotional distress. Policy implications are discussed in light of immigration reform and restrictions on eligibility for health insurance coverage for older adults in Mexico. Coping Strategies Utilized by Middle-Aged and Older Latino Caregivers of Loved Ones with Alzheimer's Disease and Related Dementia Abstract We aimed to explore the coping strategies utilized by Latino caregivers of people with Alzheimer's disease or related dementia (ADRD). We conducted 16 semi-structured interviews with Latinos family caregivers. The interviews explored the caregivers' experiences utilizing coping strategies. Coping strategies were identified based on a direct content analysis of the interviews. Participants were 50 to 75 years old, majority female, and from Mexico. The most common coping strategies adopted were: rationalization, social interactions, physical activity, and leisure activities. Other strategies used included avoidance, keeping busy, self-care, and spirituality or faith. Strategies such as using social interactions and spirituality and faith may be rooted in Latino cultural values such as familismo and fatalismo. The possible origin from cultural values might make some of the coping strategies more prevalent or effective in Latinos. Effective interventions aiming to reduce stress in Latino caregivers should prioritize culturally relevant problem-focused coping strategies. Differences within Differences: Gender Inequalities in Caregiving Intensity Vary by Race and Ethnicity in Informal Caregivers Abstract Among the 50+ million informal caregivers in the US, substantial gender, racial/ethnic, and socioeconomic disparities in caregiving intensity are well-documented. However, those disparities may be more nuanced: gender disparities in caregiving intensity may vary by race/ethnicity (White, Black, and Hispanic) and socioeconomic status (SES). We used data from the 2011 National Study of Caregiving and applied generalized linear models to estimate associations between three measures of caregiver intensity (ADLs, IADLs, and hours caregiving/month) and the three sociodemographic factors with their interaction terms. Black female caregivers provided significantly higher levels of care than White females and males for both IADL caregiving and hours/month spent caregiving. Black caregivers spent an average of 28.5 more hours/month (95%CI 1.7–45.2) caregiving than White caregivers. These findings highlight the need to understand the complex disparities within population subgroups and how intersections between gender, race/ethnicity, and SES can be used to develop effective policies to reduce disparities and improve caregiver quality-of-life. Family-Centred Interventions for Elder Abuse: a Narrative Review Abstract Information about elder abuse has not only been sparse due to factors such as underreporting or lack of standardized research, but also in defining elder abuse. However elder abuse is commonly understood to be a single/repeated act, or lack of appropriate action, occurring within any relationship which embodies an expectation of trust, which causes harm or distress to elderly individual. In elder abuse, the relationship of trust usually entails the family, as it family members who are noted to be the most likely perpetrators of elder abuse With the increased prevalence of elder abuse in developed countries and a proclivity towards individualized interventions, this narrative review sought to explore family-centered interventions used to address elder abuse by using a RE-AIM framework. Environmental Challenges in the Home for Ageing Societies: a Comparison of Sweden and Japan Abstract Sweden and Japan are developed welfare countries facing serious societal and public health challenges due to demographic ageing. The objective of the present study was to provide a background to environmental challenges in the home, related to demographic ageing. Specific aims were to compare: 1) demography and household composition 2) physical housing stocks 3) indoor accidents and 4) housing adaptations between the two countries. Descriptive analyses were conducted using secondary data sources. Demographic ageing is projected to accelerate faster in Japan compared to Sweden, with overall lower fertility rates expected in Japan. In 2050, 39% of the Japanese population is projected to be aged 65 years or older, compared to 23% of the Swedish population. The Swedish ordinary housing stock was markedly older than the Japanese housing stock, with almost 80% of the dwellings built before 1980, while in Japan about 65% were built after 1980. High occurrences of fatal indoor accidents were noted in both countries, but for different reasons. In Sweden, falls was the dominant cause of fatal accidents among older people, while in Japan, in addition to falls, drowning and suffocation caused most of the fatal accidents. Housing adaptations were less frequent in Japan compared to Sweden, and the procedure for evaluating, granting and carrying out housing adaptations appeared to be more complicated in Japan. To decrease the occurrence of indoor accidents, identifying and removing "risk barriers" could be instrumental. In both countries, large-scale efforts are imperative to improve the housing situation for the ageing population.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Effect of quality-switched laser exposure in patients with history of edible gold consumption Abstract Injectable gold is known to deposit in the dermis for life, and such patients are at risk of developing chrysiasis post-laser exposure. It is unknown if patients with history of edible gold consumption would develop a similar reaction after quality-switched laser exposure. Our aim is to assess if patients with history of edible gold consumption develop chrysiasis after quality-switched laser exposure. This is a proof of concept pilot study conducted between September 2017 and September 2018 at two dermatology clinics in Riyadh, Saudi Arabia. Adult patients who have history of edible gold consumption were recruited to receive a spot test with different quality-switched lasers in a hidden, non-sun-exposed skin site. The test area was photographed before, immediately after, and 10 min after laser exposure. The test area was examined by two independent investigators for the development of chrysiasis. A total of 10 patients (five male and five female) were enrolled. The mean age was 31.7 years. Forty percent of subjects consumed edible gold more than once, and the duration of last intake ranged from 3 weeks to 3 months. Chocolate was the main source of edible gold. All participants had no chrysiasis reaction post-quality-switched laser exposure. Contrary to our hypothesis, all participants with history of short-term edible gold consumption did not develop chrysiasis after quality-switched laser exposure. Further controlled studies including more patients with longer duration and higher frequency of edible gold consumption are needed. Combination laser therapy as a non-surgical method for treating congenital melanocytic nevi from cosmetically sensitive locations on the body Photobiomodulation-induced analgesia in experimental temporomandibular disorder involves central inhibition of fractalkine Abstract Temporomandibular disorder (TMD) is a collective term that encompasses a set of clinical problems that affect the masticatory muscles, the temporomandibular joint, and associated structures. Despite their high clinical prevalence, the mechanisms of chronic craniofacial muscle pain are not yet well understood. Treatments for TMD pain relief and control should be minimally invasive, reversible, and conservative. Photobiomodulation (PBM) is a promising option once it is known to inhibit inflammatory response and to relief painful symptoms. Herein, the effects of PBM (660 nm, 30 mW, 16 J/cm2, 0.2 cm2, 15 s in a continuous frequency) on the pain sensitivity of rats submitted to an experimental model of TMD induced by CFA was evaluated. Experimental TMD was induced in rats by the injection of complete Freund's adjuvant (CFA) injection into the masseter muscle. Nociceptive behavior was evaluated by electronic von Frey before CFA and after 1 h, 3 h, 6 h, and 24 h and 7, 14, and 21 days after PBM treatment. Inflammatory infiltrate was evaluated by histology of the masseter muscle and fractalkine expression was evaluated by immunohistochemistry of the trigeminal ganglia. PBM reversed the mechanical hypersensitivity of the animals by inhibiting the local inflammatory response, observed by the decrease of the inflammatory infiltrate in the masseter muscle of rats and by a central inhibition of fractalkine observed in the trigeminal ganglion. These data provide new insights into the mechanisms involved in the effects of photobiomodulation therapy emphasizing its therapeutic potential in the treatment of TMD. Early intervention with pulse dye and CO 2 ablative fractional lasers to improve cutaneous scarring post-lumpectomy: a randomized controlled trial on the impact of intervention on final cosmesis Abstract Light-based modalities appear to be effective for ameliorating surgical scar appearance; however, protocols for achieving such outcomes have yet to be established. We studied the safety and efficacy of a combination of pulsed dye laser (PDL) and fractional ablative CO2 laser (FACL) for the attenuation of post-lumpectomy scarring. We conducted a prospective, evaluator-blinded, comparative split-scar study in post-lumpectomy patients. One-half of the scar was treated with three sessions of 595-nm PDL and FACL at 1-month intervals, starting within 6 weeks after suture removal. The entire scar was also treated with standard moisturizers and silicone gels. Six months after the last treatment, the two halves of the scar were assessed by three uninvolved physicians who used the Observer Scar Assessment Scale as well as by the patients who used the Patient and Observer Scar Assessment Scale. Eighteen female patients (mean age, 51.3 years) with a mean scar length of 7.8 cm completed the treatment and follow-up. Six months after the last treatment, both the physician evaluators and the patients noted significant improvements for all assessed scar parameters in the laser-treated scar area compared with the untreated scar area. The treatment was well tolerated, and no remarkable adverse events were reported. All 18 participants were satisfied with the treated scar areas. A combination PDL and FACL protocol starting up to 6 weeks after suture removal is a safe and effective method for the attenuation of post-lumpectomy scar formation. Topical and intradermal delivery of PpIX precursors for photodynamic therapy with intense pulsed light on porcine skin model Abstract In order to purposely decrease the time of the photodynamic therapy (PDT) sessions, this study evaluated the effects of PDT using topical and intradermal delivery of two protoporphyrin (PpIX) precursors with intense pulsed light (IPL) as irradiation source. This study was performed on porcine skin model, using an IPL commercial device (Intense Pulse Light, HKS801). IPL effect on different administration methods of two PpIX precursors (ALA and MAL) was investigated: a topical cream application and an intradermal application using a needle-free, high-pressure injection system. Fluorescence investigation showed that PpIX distribution by needle-free injection was more homogeneous than that by cream, suggesting that a shorter drug-light interval in PDT protocols is possible. The damage induced by IPL-PDT assessed by histological analysis mostly shows modifications in collagens fibers and inflammation signals, both expected for PDT. This study suggested an alternative protocol for the PDT treatment, possibility half of the incubation time and with just 3 min of irradiation, making the IPL-PDT, even more, promising for the clinical treatment. Application of temporal correlation algorithm to interpret laser Doppler perfusion imaging A randomized, investigator-blinded, controlled, split-scalp study of the efficacy and safety of a 1550-nm fractional erbium-glass laser, used in combination with topical 5% minoxidil versus 5% minoxidil alone, for the treatment of androgenetic alopecia Abstract Fractional 1550-nm erbium-glass (Er:Glass) laser therapy is effective in inducing hair regrowth. Combining fractional Er:Glass laser therapy with topical minoxidil may yield therapeutic benefits for patients with androgenetic alopecia (AGA). To compare the efficacy and safety of fractional Er:Glass laser used in combination with topical 5% minoxidil versus 5% minoxidil alone for the treatment of male AGA, 30 men with AGA were randomized to 24 weeks of split-scalp treatment using fractional Er:Glass laser and 5% minoxidil on one side (combined therapy) or 5% minoxidil alone on the other side (monotherapy). The primary outcome was the difference in hair density and diameter, from baseline, between two treatment sides, at week 24. The secondary outcome was a global photographic assessment, evaluated by two dermatologists and the participants. Adverse events were evaluated. Twenty-nine participants completed the 24-week study period. Combination therapy provided significantly superior results for both the primary and secondary outcomes (all p < 0.05). No serious adverse events were identified for either treatment. In conclusion, combination therapy, consisting of fractional Er:Glass laser and topical minoxidil, is a promising treatment option for AGA. Laser-induced photothermolysis and the formation of effective routes for transdermal drug delivery are possible mechanisms. clinicaltrials.in.th, identifier TCTR20160912001 Label-free diagnosis of lung cancer with tissue-slice surface-enhanced Raman spectroscopy and statistical analysis Abstract Despite the rapid development of medical science, the diagnosis of lung cancer is still quite challenging. Due to the ultrahigh detection sensitivity of surface-enhanced Raman spectroscopy (SERS), SERS has a broad application prospect in biomedicine, especially in the field of tumor blood detection. Although Raman spectroscopy can diagnose lung cancer through tissue slices, its weak cross sections are problematic. In this study, silver nanoparticles (AgNPs) were added to the surface of lung tissue slices to enhance the Raman scattering signals of biomolecules. The electromagnetic field distribution of AgNPs prepared was simulated using the COMSOL software. SERS obtained from the slices reflected the difference in biochemical molecules between normal (n = 23) and cancerous (n = 23) lung tissues. Principal component-linear discriminate analysis (PCA-LDA) was utilized to classify lung cancer and healthy lung tissues. The receiver operating characteristic curve gave the sensitivity (95.7%) and specificity (95.7%) of the PCA-LDA method. This study sheds new light on the general applicability of SERS analysis of tissue slices in clinical trials. Different photodynamic effects of blue light with and without riboflavin on methicillin-resistant Staphylococcus aureus (MRSA) and human keratinocytes in vitro Abstract Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of infections in humans. Photodynamic therapy using blue light (450 nm) could possibly be used to reduce MRSA on different human tissue surfaces without killing the human cells. It could be less harmful than 300–400 nm light or common disinfectants. We applied blue light ± riboflavin (RF) to MRSA and keratinocytes, in an in vitro liquid layer model, and compared the effect to elimination using common disinfection fluids. MRSA dilutions (8 × 105/mL) in wells were exposed to blue light (450 nm) ± RF at four separate doses (15, 30, 56, and 84 J/cm2). Treated samples were cultivated on blood agar plates and the colony forming units (CFU) determined. Adherent human cells were cultivated (1 × 104/mL) and treated in the same way. The cell activity was then measured by Cell Titer Blue assay after 24- and 48-h growth. The tested disinfectants were chlorhexidine and hydrogen peroxide. Blue light alone (84 J/cm2) eliminated 70% of MRSA. This dose and riboflavin eradicated 99–100% of MRSA. Keratinocytes were not affected by blue light alone at any dose. A dose of 30 J/cm2 in riboflavin solution inactivated keratinocytes completely. Disinfectants inactivated all cells. Blue light alone at 450 nm can eliminate MRSA without inactivation of human keratinocytes. Hence, a high dose of blue light could perhaps be used to treat bacterial infections without loss of human skin cells. Photodynamic therapy using riboflavin and blue light should be explored further as it may perhaps be possible to exploit in treatment of skin diseases associated with keratinocyte hyperproliferation. Fractional carbon dioxide laser and topical tioconazole in the treatment of fingernail onychomycosis Abstract Onychomycosis is a common chronic-resistant nail disease. Traditional treatment has its limitations and side effects. This study aimed to evaluate the role of fractional CO2 laser and topical tioconazole 28% nail lacquer in the treatment of fingernail onychomycosis, as sole treatment modalities and in combination. Thirty patients with culture-proven onychomycosis were included and randomly divided into three equal groups. Laser group received six fractional carbon dioxide (CO2) laser sessions at monthly intervals; topical group received topical tioconazole 28% nail lacquer twice daily for 6 months, and combined group received six fractional CO2 laser sessions at monthly intervals with topical tioconazole twice daily for 6 months. Treatment outcome was evaluated through physician's evaluation of improvement using onychomycosis severity index score (OSI), patients' satisfaction, side effect evaluation, and mycological culture (assessed after the end of treatment). At the end of treatment, both laser and combined groups showed significantly better degrees of improvement (P = 0.036, 0.024, respectively) and patient's satisfaction (P = 0.046, 0.003, respectively) in comparison with topical group. Mycological clearance in fungal cultures was significantly higher in combined group than topical group after the end of treatment (P = 0.007). Fractional CO2 laser is a safe and effective treatment modality for onychomycosis. Its efficacy approximates that of fractional CO2 laser combined with topical tioconazole 28% nail lacquer and surpasses that of topical tioconazole 28% monotherapy. It is expected to be an excellent choice for patients in whom systemic antifungals are contraindicated or who are unresponsive or intolerant to topical antifungals.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Adult Granulosa Cell Tumor of Ovary: Clinical Study of 10 Cases AbstractPurpose To evaluate the clinicopathological entities of adult granulosa cell tumor of ovary.Method A retrospective analysis of ten cases of adult granulosa cell tumor of ovary managed in a tertiary care center (VPS Lakeshore hospital, Kochi) from 2004 to 2018.Results Ten cases were identified to have adult granulosa cell tumor (GCT). Mean age was 45.3 years (range 31–63 years). Irregular cycles, palpable mass and pain abdomen were presenting complains. Palpable abdomino-pelvic mass was present in 7 (70%). Only one case had preoperative rise in serum Ca125 level. Serum inhibin analysis was done in postoperative period only, and one case had raised inhibin. Out of ten cases, 6 underwent laparoscopic surgery for adnexal mass and diagnosis of GCT was made in the final histopathology report. Five of them underwent completion surgery later on. Adjuvant chemotherapy was given in three of the cases. Total of 7 cases (70%) had recurrence. Pelvis was common site of recurrence, and mean duration of recurrence was 5.08 years (24–132 months). Mean disease-free period was 3.97 years (6–132 months). There were four mortalities. The longest follow-up duration for single case till the date was 13 years with recurrence in between.Conclusion Granulosa cell tumor of ovary is rare form of ovarian malignancy. Stage is the important prognostic factor. It has good prognosis compared to epithelial ovarian neoplasm. It is difficult to predict preoperatively. Care should be taken to prevent spillage while dealing with adnexal mass which occurs commonly in minimal access surgery and mini-laparotomy. Addition of Etoricoxib During Concurrent Chemo-radiation of Cervical Cancer Patients Could Result in Faster Resolution of Gross Disease: A Prospective Single-Institution Study AbstractObjective A prospective study was conducted to assess the effect of adding COX-2 inhibitor Etoricoxib during concurrent chemo-radiotherapy schedule of cervical cancer patients on tumour response and acute toxicities.Materials and Methods Forty patients of carcinoma cervix [mostly locally advanced] were treated using external beam radiotherapy (EBRT) [telecobalt, 45 Gy/20F/5F per week] concurrent with weekly cisplatin- or cisplatin + paclitaxel-based chemotherapy. Low-dose-rate (LDR) intracavitary brachytherapy (ICBT) 30 Gy to point A was delivered in between EBRT fractions in a single setting. Patients were prospectively allocated either to receive Etoricoxib 90 mg OD during the entire course of chemo-radiation [arm A] or not [arm B]. Weekly assessment with clinical evaluation and routine blood tests were done during the course of treatment, with pre-ICBT clinical evaluation taken into consideration for disease response comparison between arms.Results When evaluated clinically before intracavitary brachytherapy procedure, the gross disease was found to have regressed more in the arm receiving Etoricoxib [p = 0.042]. Acute grade-3 toxicities ranged between 5 and 15% for patients who received Etoricoxib and 10–15% for those who did not. Difference in toxicities was not statistically significant.Conclusion Addition of COX-2 inhibitor [Etoricoxib] during concurrent chemo-radiation results in a faster response of the primary disease in locally advanced cervical cancer patients, without a significant difference in acute toxicities. A Suggested Strategy to Reduce Stump Carcinoma After Performing "Obligatory" Subtotal Hysterectomy Patterns of First Relapse and Outcome in Patients with Locally Advanced Cervical Cancer After Radiochemotherapy: A Single Institutional Experience AbstractPurpose Radiochemotherapy followed by brachytherapy is the standard treatment in locally advanced cervical cancer. The aim of this study was to evaluate the patterns of first relapse, the treatment given and its outcome.Methods This is a retrospective analysis of electronic records of locally advanced cervical cancer patients treated in prospective trials from 2003 to 2014.Results Out of 1388 patients, relapse was seen in 316 (23%). Relapse was seen as—pelvic: 105 (7.6%), distant: 136 (10%), and both: 75 (5.4%). Local, regional, paraaortic and systemic relapses were seen in 148 (10.8%), 65 (4.7%), 102 (7.4%) and 163 (11.8%) patients, respectively. Post-relapse, 201/316 (63.6%) received palliative care alone. Treatment in the form of concurrent or sequential chemo-radiotherapy, surgery, stereotactic body radiotherapy and reirradiation using brachytherapy was received by 15 (4.7%), 7 (2.2%), 1 (0.3%) and 1(0.3%) patients, respectively; 65 (20.6%) received palliative chemotherapy, and 28 (8.9%) received palliative radiotherapy. Median post-relapse survival was 7 months (95% CI 5.9–8.1); and in those who received treatment versus supportive care was 10 (95% CI 7.0–13.0) versus 5 (95% CI 3.9–6.1) months (p < 0.001). The proportion of patients with > 1-year post-relapse survival was 85.7% in surgery, 66.7% in concurrent or sequential chemotherapy plus radiation, 32.3% in palliative chemotherapy, 14.3% in palliative radiotherapy and 13.4% in supportive care.Conclusion Distant failure is the predominant pattern of relapse seen in patients undergoing radiochemotherapy for locally advanced cervical cancer. Well-selected single-site relapses treated with surgery or chemotherapy plus radiation can have good post-relapse survival. Challenges in Detection and Management of Pre-invasive Glandular Lesions of the Cervix Abstract Despite the success of cervical screening, we continue to see an increase in pre-invasive glandular lesions, and subsequent adenocarcinomas of the cervix. Atypical glandular cells are reported in approximately 0.17–0.6% of cervical cytology samples; up to one-third have underlying pathology that requires further treatment. Glandular lesions of the cervix present unique diagnostic and therapeutic challenges. Colposcopy is often less reliable for assessment of glandular lesions. The role of HPV testing and ECC in diagnosis and surveillance is unclear. Conventional belief is that cold knife conization is superior to LEEP for management of adenocarcinoma in situ (AIS); however, more recent reviews suggest the procedures are oncologically equivalent so long as margins are interpretable and negative. As many young women with AIS desire fertility preservation, evidence on oncologic and obstetric outcomes following conservative management is emerging. The purpose of this review is to discuss some of the common challenges, from a clinician's perspective, around detection and management of pre-invasive lesions of the cervix. Editorial Technical Aspects of Endosurgical Extraperitoneal Aortic Lymph Node Dissection in Gynaecologic Oncology AbstractIntroduction Laparoscopic aortic node dissection can be performed using extraperitoneal techniques. The surgical technique has been made much easier by the development of multifunction instruments, combining sophisticated bipolar thermal fusion and sharp incision, or using harmonic hemostasis. These instruments improve ergonomy, and may reduce the lymphocyst formation rate, the more frequent complication of extraperitoneal lymph node dissection. Robotic assistance is feasible and safe, but that does not provide significant improvement in perioperative outcomes. Laparoscopic or robot-assisted single port has been used by several investigators, which led to the same conclusions. Interestingly, the left lateral extraperitoneal approach can be extended to the left pelvic sidewall, allowing to resect suspicious nodes, sentinel nodes or to complete left pelvic lymph node dissection.Materials and Methods In this paper, a review of the technical aspects including surgical steps, instrumentation, and comparative studies of perioperative outcomes has been carried out. A PubMed search was carried out from the year 1995, including the terms "extraperitoneal" "aortic" "lymph node dissection". Comparative studies investigating the benefits of the extraperitoneal approach compared to the transperitoneal approach were carefully screened. One animal randomized study and one clinical randomized study are available, along with meta-analyses or reviews of retrospective comparative studies.Results No difference was observed in terms of duration of the surgery, blood loss, postoperative complications, hospital stay, and node yield. The extraperitoneal technique overall generates less adhesions, and the intraoperative complication rate is significantly lower than in the transperitoneal approach. The proportion of patients in whom the operation can be satisfactorily completed by this approach is over 90%. The advantages of the extraperitoneal approach are more in obese patients, in relation to the absence of interference of the bowel loops in the operative field, and a higher feasibility.Conclusion The extraperitoneal endosurgical approach is an indispensable tool which must be mastered by gynaecologic oncologists. Extraperitoneal aortic lymph node dissection can be used as a staging procedure, or a part of a full endoscopic operation encompassing intraperitoneal steps like omentectomy and hysterectomy in the surgical staging of endometrial and ovarian cancer. Surgery for Cervical Cancer: Perspectives from Low- and Middle-Income Countries AbstractPurpose This review and opinion provides a very brief overview of current thinking about surgery for cervical cancer. The aim is to add the perspectives of gynaecologic oncologists working in low- and middle-income countries and consider where these may differ from the oft-quoted perspectives of professionals in high-income settings.Methods This article firstly explores aspects of cervical cancer and its treatment that differ between low- and middle-income countries (LMICs) and high-income countries. Secondly, newer developments in the surgical management of primary and recurrent cervical cancers are considered. Lastly, it is discussed where and why perspectives from LMIC may be different from the 'global standard'.Results The reader will be challenged to rethink the applicability of widely published current opinions to all areas in the world. It is acknowledged that LMIC represents a large spectrum over multiple continents and that considerations will not apply to all settings. Some developments may be detrimental to countries without disease control, while other concepts offer hope and innovation.Conclusion Different conditions in LMIC and the solutions found by health professionals working there, must be noted by the wide fraternity as a contribution to science. Adherence to global guidelines should not be expected. Making of a Gynecologic Oncologist Abstract It takes a special person to be a gynecologic oncologist, requiring special surgical skills, empathy and knowledge of female cancer. American Board of Obstetrics and Gynecology started a division of subspecialty in gynecology oncology in 1974 to train gynecologic oncologists in taking care of women with gynecologic malignancies. The curriculum was developed for candidates in training, and institutes were selected based on their expertise and availability of surgical, chemotherapy and radiation specialists following their board certification in obstetrics and gynecology. This article specifies all the current requirements and what it takes to be a gynecological oncologist for a person who is certified in obstetrics and gynecology and fits the criteria to become a gynecologic oncologist. Review of the Outcomes of Ovarian Cancer Treated with Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy Abstract Ovarian, fallopian tube and primary peritoneal carcinomas (OVCA) most commonly present in advanced stages and despite aggressive surgical resection and chemotherapy will likely recur. Although OVCA can recur in the liver, chest or brain, it most commonly recurs within the peritoneal cavity. Peritoneal spread is problematic and often results in bowel obstruction and the inability to maintain nutritional goals. Given the lethality of peritoneal disease as well as the difficulty in treating this recurrence pattern, novel tactics to treat peritoneal dissemination have been a focus of research in OVCA. Heated intraperitoneal chemotherapy (HIPEC) has been well studied and is utilized to treat appendiceal malignancies, which similarly involve the peritoneum. HIPEC has been shown to improve survival and decrease the risk of peritoneal recurrence in patients with appendiceal malignancies. This technique has also been shown to improve outcomes in patients with peritoneal metastases due to colorectal cancers and gastric cancers. Over the past three decades, HIPEC has been used to treat OVCA with mixed results. The aim of this paper is to review the use of HIPEC in the treatment of OVCA in the upfront and recurrent setting.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Association of daily physical activity with cognition and mood disorders in treatment-naive patients with early-stage Parkinson's disease Abstract To determine the association of daily physical activity with cognition, mood disorders, and olfactory function in treatment-naive patients with early-stage Parkinson's disease (PD). The study subjects were 52 treatment-naive patients with early-stage PD (< 80 years). Daily physical activity was measured using a wearable sensor with a built-in triaxial accelerometer, and its association with cognition [mini-mental state examination (MMSE), clock-drawing test (CDT), frontal assessment battery (FAB), and behavioral assessment of the dysexecutive syndrome (BADS)], depressive symptoms [Beck Depression Inventory-Second Edition (BDI-II)], apathy [Starkstein Apathy Scale (AS)], and olfactory function [Odor Stick Identification Test for the Japanese (OSIT-J)] was analyzed using multiple linear regression after adjustment for age, sex, and education status. The daily physical activity (0.42 ± 0.11 m/s2) of the PD group was significantly lower than that of healthy controls (p < 0.001). Moreover, the daily physical activity of the PD group was significantly associated with FAB (β = 0.337, p = 0.027) and BADS (β = 0.374, p = 0.017) scores, but not with MMSE, CDT, BDI-II, AS, and OSIT-J scores. The daily physical activity is significantly reduced in treatment-naive patients with early-stage PD, and the low activity correlates with frontal/executive function. Macular ganglion-cell-complex layer thinning and optic nerve integrity in drug-naïve Parkinson's disease Abstract To reveal the macular inner retinal change linked to axonal degeneration in Parkinson's disease (PD), we performed macular optical coherence tomography scan and diffusion tensor imaging of the retrobulbar optic nerve on both eyes of 36 drug-naïve PD patients. Thicknesses of inner retinal layers were automatically measured, and correlation analysis was conducted between the retinal thickness and diffusion parameters of the optic nerve. PD patients showed thinning of the inner retinal layers compared to control data. Thicknesses of the ganglion cell and inner plexiform layers were both correlated positively with fractional anisotropy and negatively with diffusivity indices of ipsilateral optic nerve (FDR-adjusted p < 0.05). This study revealed a novel in vivo connection between macular parafoveal ganglion cell change and integrity in the retrobulbar optic nerve in drug-naïve PD. Molecular determinants of behavioral changes induced by neonatal ketamine and dexmedetomidine application Abstract Ketamine (KET), an anesthetic, analgesic, and a sedative N-methyl-d-aspartate (NMDA) receptor antagonist agent, exposure during neonatal period may lead to learning impairment, behavioral abnormalities, and cognitive decline in the later years of life. In recent studies, it has been reported that sedative-acting α2 agonist dexmedetomidine (DEX), which is commonly used in clinical practice with KET, has neuroprotective effects and prevents the undesirable effects of anesthesia. To elucidate the underlying mechanisms of these actions, we investigated the interaction between NMDA receptors α2 adrenoceptor and adulthood behaviors in neonatally KET and/or DEX administrated mice. Balb/c male mice were administrated with saline, KET (75 mg/kg), DEX (10 µg/kg), or KET + DEX (75 mg/kg + 10 µg/kg) on postnatal day 7. During adulthood (8–10 weeks old) mice were subjected to elevated plus maze, open field, and Morris water maze tests. After behavioral tests, hippocampus samples were extracted for mRNA expression studies of NMDAR subunits (GluN1, GluN2A, and GluN2B) and α2 adrenoceptor subunits (α2A, α2B, and α2C) by real-time PCR. Ketamine increased horizontal and vertical locomotor activity (p < 0.01) and impaired spatial learning-memory (p < 0.05). DEX increased anxiety-like behavior (p < 0.01), but did not affect spatial learning-memory and locomotor activity. KET + DEX impaired spatial learning-memory (p < 0.01), increased horizontal locomotor activity (p < 0.01), and anxiety-like behavior (p < 0.05). Our study implies that DEX cannot prevent the adverse effects of KET, on spatial learning-memory, and locomotor activity. In addition to this, it can be thought that during brain development, there is an interaction between NMDAR and α2 adrenoceptor systems. Mesenchymal stem cells inhibited the inflammation and oxidative stress in LPS-activated microglial cells through AMPK pathway Abstract Microglia are the resident mononuclear immune cells of the central nervous system (CNS) and the activation of microglia contributes to the production of excessive neurotoxic factors. In particular, the overproduction of neurotoxic factors has critical effects on the development of brain injuries and neurodegenerative diseases. The human bone marrow-derived mesenchymal stem cells (hBM-MSCs) have blossomed into an effective approach with great potential for the treatment of neurodegenerative diseases and gliomas. The present study aimed to investigate the mechanism behind the therapeutic effect of hBM-MSCs on the activation of microglia in vitro. Specifically, the hBM-MSCs significantly inhibited the proliferation of lipopolysaccharide-activated microglial cells (LPS)-activated microglial cells. Additionally, we investigated whether the adenosine-monophosphate-activated protein kinase signaling (AMPK) pathway was involved in this process. Our data demonstrated that hBM-MSCs significantly increased the phosphorylated AMPK in LPS-activated microglial cells. In addition, our study indicated the inhibitory effect of hBM-MSCs on the pro-inflammatory mediators and oxidative stress by the AMPK pathway in LPS-activated microglial cells. These results could shed light on the understanding of the molecular basis for the inhibition of hBM-MSCs on LPS-activated microglial cells and provide a molecular mechanism for the hBM-MSCs implication in brain injuries and neurodegenerative diseases. Association between cognitive performance and SYT1 -rs2251214 among women with cocaine use disorder Abstract The SNP rs2251214 of the SYT1 gene was recently associated with externalizing phenotypes, including ADHD and cocaine use disorder (CUD). Here, we investigated whether SYT1-rs2251214 could also be implicated with cognitive performance variations among women with CUD. Results showed that G homozygous (n = 146) have lower cognitive performance in the Stroop, Trail Making and Matrix Reasoning tests compared with A-allele carriers (n = 64), suggesting that rs2251214 may influence the severity of cognitive impairments in CUD. Vitamin D rise enhances blood perfusion in patients with multiple sclerosis Abstract The chemical structure of vitamin D resembles steroids and anabolics. Following activation by enzymatic hydroxylation, vitamin D enhances numerous body functions. We determined 25-hydroxy-vitamin D, number of erythrocytes, haematocrit, mean corpuscular haemoglobin and mean corpuscular volume in 97 patients with multiple sclerosis initially and 6 months later. Patients with deficient levels of 25-hydroxyvitamin D (< 30 ng/mL) were advised to perform vitamin D supplementation and received a prescription of a vitamin D formulation. Six months later we observed a rise of 25-OH-vitamin D, as to be expected, and a modified constellation of blood parameters such as elevation of mean corpuscular haemoglobin concentration and fall of mean corpuscular volume. Mean corpuscular haemoglobin and number of erythrocytes remained stable. The haematocrit went down. We suggest that vitamin D elevation may be beneficial in disorders characterised by chronic neuroinflammation and neurodegeneration, since changes of blood perfusion parameters may enhance cellular tissue oxygenation. Comparing lanbotulinumtoxinA (Hengli ® ) with onabotulinumtoxinA (Botox ® ) and incobotulinumtoxinA (Xeomin ® ) in the mouse hemidiaphragm assay Abstract LanbotulinumtoxinA (LAN) is manufactured and registered in China since 1994. Despite its widespread use in China and its increasing use in other Asian countries and in South America, it is not yet well known elsewhere. We wanted to compare its potency labelling using the mouse diaphragm assay (MDA), an isolated muscle model for botulinum toxin (BT) potency measurements, which is superior to clinical tests and which was recently refined as an alternative batch release assay for BT manufacturing. We also wanted to estimate LAN manufacturing quality by testing its inter-batch potency consistency. Potencies of 20, 60 and 100 MU of LAN, onabotulinumtoxinA (ONA) and incobotulinumtoxinA (INCO) were measured by the inversely related paresis time (PT) in the MDA. The PT (M ± SD) of all doses of LAN, ONA and INCO was 90.4 ± 27.0 min, 114.9 ± 46.5 min and 94.3 ± 29.9 min, respectively. Statistical analysis demonstrated indistinguishable potency labelling of LAN and INCO, but revealed a slightly lower potency of ONA compared to LAN and INCO. PT of LAN batch 1 and LAN batch 2 was 86.9 ± 21.2 min and 94.0 ± 32.8 min, respectively (no statistically significant difference), suggesting an adequate LAN manufacturing consistency. The MDA is an appropriate instrument for potency testing of BT drugs, including new ones currently under development. Our results allow comparing therapeutic effects, adverse effects and economics of LAN, ONA and INCO. They also suggest adequate manufacturing consistency of LAN. Theta burst stimulation for the treatment of obsessive–compulsive disorder: a pilot study Abstract A non-negligible part of patients with obsessive–compulsive disorder (OCD) experiences inadequate response to pharmacological and cognitive therapies. Therefore, new approaches are required to overcome this problem. The present pilot study estimates the capacity of theta burst stimulation (TBS) in reducing OCD symptoms, also focusing on the neurophysiological basis of TBS aftereffects. Ten patients with OCD who were unsatisfactorily responsive to the pharmacological and neuropsychological treatment, participated to the present randomized crossover pilot study, in which they were subjected to a real or sham intermittent TBS (iTBS) paradigm over the left dorsolateral prefrontal cortex (L-DLPFC) as add-on treatment. They were randomly assigned to a real or sham iTBS in a 1:1 allocation ratio. Patients received the TBS treatment every morning, 5 days a week for 1 month, and were clinically and electrophysiologically evaluated (EEG phase synchronization and coherence) before, immediately after (T0), and one (T1), three (T3) and six (T6) months after the end of the TBS treatment. Then, each patient was subjected to the alternative treatment (that was not practiced before), and followed up to 6 months. We found that all the patients improved in OCD symptomatology up to T1, while four among them improved up to T3. These patients were those showing a more extensive reshape of frontal areas phase synchronization and frontoparietal coherence compared to the other participants. Our pilot study suggests that iTBS over L-DLPFC may represent a feasible approach to improve OCD symptoms. The efficacy of iTBS seems to depend on the extent of frontal and frontoparietal connectivity modulation. Covariation bias in depression - a predictor of treatment response? Abstract Covariation bias, defined as an overestimation of the relationship between fear-relevant stimuli and aversive consequences, is a well-investigated cognitive bias in anxiety disorders. As patients with affective disorders also show biased information processing, the aim of the present study was to investigate whether depressed patients also display a covariation bias between negative stimuli and aversive consequences. Covariation estimates of 62 inpatients with a current severe depressive episode were assessed at admission (n = 31) or after 6 weeks of treatment (n = 31) and were compared in a between-group design with 31 age- and sex-matched healthy controls. All participants showed a covariation bias for the relationship between negative stimuli and aversive consequences. Moreover, covariation bias at admission was significantly associated with various clinician- and self-reported dimensional measures of treatment response assessed 6 weeks later (Global Assessment of Functioning, Clinical Global Impression Scale, and Beck Depression Inventory), i.e., patients with a stronger bias showed greater impairment after 6 weeks of treatment. Categorical analyses revealed that overall, treatment non-responders—but not responders—were characterized by a covariation bias. The naturalistic study design without standardized pharmacological and psychotherapeutic treatments is a central limitation. We conclude that the covariation bias may constitute a possible marker in the field of emotional information processing in the search for effective predictors of therapy outcome. High ultrasensitive serum C-reactive protein may be related to freezing of gait in Parkinson's disease patients Abstract C-reactive protein (CRP) is a biomarker of systemic inflammation that has been linked to accelerated decline in walking speed in older adults. The aim of the present study was to compare the CRP levels of PD patients with vs patients without freezing of gait (FOG). Patients and controls participating in the COPPADIS-2015 study that performed blood extraction for determining molecular serum biomarkers were included. Patients with FOG were identified as those with a score of 1 or greater on item-3 of the Freezing of Gait Questionnaire (FOG-Q). Immunoassay was used for determining ultrasensitive CRP (US-CRP) level (mg/dL). In the PD group (n = 225; 61.8 ± 9.5 years old, 61.8% males), 32% of the patients presented FOG but none in the control group (n = 65; 60.3 ± 6.1 years old, 56.9% males) (p < 0.0001). Differences in US-CRP level were significant in patients with FOG vs patients without FOG and vs controls (0.31 ± 0.52 vs 0.16 ± 0.21 vs 0.21 ± 0.22; p = 0.04). Significant differences were also observed between patients with vs without FOG (p = 0.001) but not between patients and controls (p = 0.163). US-CRP level was related to FOG (OR = 4.369; 95% CI 1.105–17.275; p = 0.036) along with H&Y (OR = 2.974; 95% CI 1.113–7.943; p = 0.030) and non-motor symptoms burden (NMSS total score; OR = 1.017; 95% CI 1.005–1.029; p = 0.006) after adjusting for age, gender, disease duration, equivalent daily levodopa dose, number of non-antiparkinsonian drugs per day, motor fluctuations, cognition, motor phenotype, and chronic use of anti-inflammatory drugs. The present study suggests that serum US-CRP level is related to FOG in PD patients. Inflammation could be linked to FOG development.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

08:50

Diagnosis of coronary artery disease in patients with atrial fibrillation using low tube voltage coronary CT angiography with isotonic low-concentration contrast agent Abstract This prospective study evaluated the image quality and accuracy of coronary computed tomography angiography (CCTA) for diagnosing coronary artery disease (CAD) in patients with atrial fibrillation (AF), in which CCTA used adaptive iterative dose reduction (AIDR) with a low tube voltage and low concentration of isotonic contrast agent. Sixty-eight consecutive patients with AF and suspected CAD were equally and randomly apportioned to two groups and underwent CCTA. In the experimental group, the contrast agent was iodixanol (270 mg I/mL), patients were scanned with 100 kV, and reconstruction was by AIDR. In the conventional scanning (control) group, the contrast agent was iopromide (370 mg I/mL), patients were scanned with 120 kV, and reconstruction was by filtered back projection. The image quality, effective radiation dose (E), and total iodine intake of the groups were compared. Thirty-nine patients with coronary artery stenosis later were given invasive coronary angiography (ICA). The groups were similar with regard to mean CT value, noise, and signal-to-noise and contrast-to-noise ratios. The figure of merit of the experimental group was significantly higher than that of the control group, while the E and total iodine were significantly lower. Using ICA as the diagnostic reference, the groups shared similar sensitivity, specificity, and false positive and false negative rates for diagnosing coronary artery stenosis. For determining CAD in patients with AF, CCTA with isotonic low-concentration contrast agent and low-voltage scanning is a feasible alternative that improves accuracy and reduces radiation dose and iodine intake. Denoising and artefact removal for transthoracic echocardiographic imaging in congenital heart disease: utility of diagnosis specific deep learning algorithms Abstract Deep learning (DL) algorithms are increasingly used in cardiac imaging. We aimed to investigate the utility of DL algorithms in de-noising transthoracic echocardiographic images and removing acoustic shadowing artefacts specifically in patients with congenital heart disease (CHD). In addition, the performance of DL algorithms trained on CHD samples was compared to models trained entirely on structurally normal hearts. Deep neural network based autoencoders were built for denoising and removal of acoustic shadowing artefacts based on routine echocardiographic apical 4-chamber views and performance was assessed by visual assessment and quantifying cross entropy. 267 subjects (94 TGA and atrial switch and 39 with ccTGA, 10 Ebstein anomaly, 9 with uncorrected AVSD and 115 normal controls; 56.9% male, age 38.9 ± 15.6 years) with routine transthoracic examinations were included. The autoencoders significantly enhanced image quality across diagnostic subgroups (p < 0.005 for all). Models trained on congenital heart samples performed significantly better when exposed to examples from congenital heart disease patients. Our study demonstrates the potential of autoencoders for denoising and artefact removal in patients with congenital heart disease and structurally normal hearts. While models trained entirely on samples from structurally normal hearts perform reasonably in CHD, our data illustrates the value of dedicated image augmentation systems trained specifically on CHD samples. Novel mesh-derived right ventricular free wall longitudinal strain analysis by intraoperative three-dimensional transoesophageal speckle-tracking echocardiography: a comparison with conventional parameters Abstract Longitudinal right ventricular (RV) function is substantial and might be reflected by free wall longitudinal strain (FWLS). Software solutions for FWLS analysis by two-dimensional (2D) and three-dimensional (3D) transesophageal echocardiography (TEE) are available, but data on validation are sparse. In this study, a novel method for FWLS analysis on 3D meshes ("mesh surface", MS-FWLS,) was tested for feasibility and compared to available parameters. 80 patients undergoing left-sided cardiac valve surgery with intraoperative TEE were included retrospectively. 2D-FWLS, 3D-derived (3Dd)-FWLS (assessed in optimized four-chamber views after volume analysis) and MS-FWLS were measured and compared to conventional parameters (3Dd-TAPSE, FAC and RVEF). The mean FWLS values did not differ significantly between methods (− 19.0 ± 6.1%, − 20.0 ± 7.3%, − 19.5 ± 7.3% for 2D-, 3Dd- and MS-FWLS, respectively). No significant differences in the mean FWLS between patients with normal or increased pulmonary artery pressures as well as normal or reduced left ventricular ejection fraction were observed. Agreement was best between 3Dd- and MS-FWLS (r = 0.89, bias = − 1.0%, LOA ± 6.9%). Conventional echocardiographic parameters yielded poorer intermodality agreement. In patients with discrepant results between 2D- and 3Dd-FWLS, 3Dd-FWLS and MS-FWLS yielded similar results (r = 0.82, bias = − 0.3%, LOA ± 8.6%), while 2D-FWLS and MS-FWLS did not. Intra- and interobserver variabilities of strain analyses were low. MS-FWLS might represent a promising method to overcome artefacts associated with 2D analysis. Its prognostic relevance needs to be investigated in prospective studies. Evaluation of left atrial volume and function in patients with coronary slow flow phenomenon using real-time three-dimensional echocardiography Abstract This study aimed to evaluate the left atrial (LA) volume and phasic functions using real-time three-dimensional echocardiography (RT3DE) in coronary slow flow phenomenon (CSFP) patients with preserved left ventricular ejection fraction (LVEF). 56 patients with CSFP (36 males, 20 females) and 48 controls with normal coronary flow (27 males, 21 females) were prospectively enrolled. Comprehensive transthoracic echocardiographic examination and RT3DE for the assessment of LA dynamics were performed in all participants. LA maximum, minimum, and pre-atrial contraction volumes (LAV-max, LAV-min, and LAV-preA) were obtained for every subject. Conventional echocardiographic parameters, except for isovolumetric relaxation time and transmitral deceleration time, did not differ in two groups. RT3DE demonstrated higher LAV-max, LAV-min, LAV-preA, indexed LAV-max (LAVi-max), LA total emptying volume, and LA active emptying volume and fraction for CSFP patients compared with controls (all P < 0.05). In addition, LA total emptying fraction and LA passive emptying fraction were found to be lower in CSFP patients than in controls (all P < 0.05). Moreover, there were positive correlations between mean thrombolysis in myocardial infarction frame count values and LAV-max, LAV-min, LAV-preA, LAVi-max, and LA total and active emptying volumes. CSFP was associated with enlarged LA volumes, impaired LA reservoir and conduit function and enhanced contractile function. Evaluation of LA dynamics using RT3DE could facilitate recognition of subtle myocardial alterations related with CSFP. Patients with high left ventricular filling pressure may be missed applying 2016 echo guidelines: a pilot study Abstract 2016 guidelines for the echographic evaluation of left ventricular filling pressure (LVFP) proposed a single algorithm with limited number of criteria (E/A ratio, tricuspid regurgitation velocity, left atrial volume index and average E/e′) mainly related to left atrial pressure. Pulmonary venous flow analysis, evaluating more specifically left ventricular end diastolic pressure (LVEDP) has been withdrawn. We aim to evaluate the proportion of patients diagnosed with normal LVFP according to 2016 recommendations, despite an abnormal pulmonary venous flow profile suggesting high LVEDP. We prospectively studied patients with stable ischemic cardiomyopathy and aortic stenosis, before cardiac surgery. Extensive echocardiography was performed including pulmonary and mitral A wave durations. We included 76 patients (mean age 72 ± 10 years, 78% were men), 37 (49%) with aortic stenosis and 22 (29%) with ischemic cardiomyopathy. Mean left ventricular ejection fraction was 67 ± 11%. Applying recommendations, 58 patients had normal LVFP and 15 patients had high LVFP. Among the 58 patients with normal LVFP, 26 patients had Apd–Amd duration > 30 ms highly suggestive of high LVEDP. These patients had higher LV mass (112 ± 30 g/m2 vs. 86 ± 20 g/m2, p = 0.004) and shorter A wave duration (120 ± 13.6 ms vs. 132 ± 16.5 ms, p = 0.006) as compared to the remaining 15 patients with concordant evaluation (normal LVFP and normal Apd–Amd). In the present study, we found that 26/58 patients with low LVFP according to the 2016 recommendations had Apd–Amd suggestive of high LVEDP. Pulmonary venous flow should be added to the algorithm, particularly in patients with unexplained symptom, high LV mass or truncated mitral A wave. Diagnostic and prognostic value of cardiac magnetic resonance in acute myocarditis: a systematic review and meta-analysis Abstract While diagnostic criteria were elaborated for acute myocarditis using cardiac magnetic resonance (CMR) in 2009, studies have since examined the yield of traditional and novel CMR parameters to achieve greater accuracy and to predict clinical outcomes. The purpose of this systematic review and meta-analysis was to determine the diagnostic and prognostic value of CMR parameters for acute myocarditis. MEDLINE and EMBASE were systematically searched for original studies that reported CMR parameters in adult patients suspected of acute myocarditis. Each CMR parameter's binary prevalence, mean value and standard deviation were extracted. Parameters were meta-analyzed using a random-effects model to generate standardized mean differences. After screening 1492 abstracts, 53 studies were included encompassing 2823 myocarditis patients and 803 controls. Pooled standardized mean differences between myocarditis patients and controls were: T2 mapping time 2.26 (95% CI 1.50–3.02), extracellular volume 1.64 (95% CI 0.87–2.42), LGE percentage 1.30 (95% CI 0.95–1.64), T1 mapping time 1.18 (95% CI 0.35–2.01), T2 ratio 1.17 (95% CI 0.80–1.54), and EGE ratio 0.93 (95% CI 0.66–1.19). Prolonged T1 mapping time had the highest sensitivity (82%), pericardial effusion had the highest specificity (99%). Baseline LV dysfunction and the presence of LGE were predictive of major adverse cardiac events. The results support integration of parametric mapping criteria in the diagnostic criteria for myocarditis. The presence of baseline LV dysfunction and LGE predict patients at higher risk of adverse events. Impact of lesion angle on optical coherence tomography findings and clinical outcomes after drug-eluting stent implantation in curved vessels Abstract Tortuous coronary lesions are associated with adverse outcomes after implantation of bare metal or first-generation drug-eluting stents (DESs). We investigated the impact of lesion angle on vessel wall injuries and stent apposition as assessed by optical coherence tomography (OCT) after second- and newer-generation DES implantation. We investigated 95 de novo lesions treated with a single DES (62 platinum-chromium everolimus-eluting stents and 33 bioresorbable-polymer sirolimus-eluting stents). Post-intervention OCT findings were compared between angled lesions (≥ 45°; n = 33) and non-angled lesions (< 45°; n = 62). The 12-month clinical outcomes were also compared between the groups. Cross-sectional OCT analysis revealed that compared to non-angled lesions, angled ones had a significantly higher incidence of intra-stent dissection around the centre of the angle (19.7% vs. 10.8%, p = 0.01) and incomplete stent apposition (ISA) in the distal and proximal sub-segments (10.0% vs. 4.1%, p = 0.002; 15.3% vs. 7.9%, p < 0.001, respectively). Strut-based analysis also showed that angled lesions demonstrated a higher rate of malapposed strut in the distal and proximal sub-segments (3.0% vs. 0.9%, p < 0.001; 4.3% vs. 1.8%, p < 0.001, respectively). The 12 month clinical outcomes were comparable between the groups. Compared to non-angled lesions, angled coronary lesions were associated with a higher incidence of intra-stent dissection and ISA on post-intervention OCT after implantation of second- and newer-generation DESs. Impact of two formulas to calculate percentage diameter stenosis of coronary lesions: from stenosis models (phantom lesion model) to actual clinical lesions Abstract Percentage diameter stenosis (%DS) by angiography is still commonly used to determine luminal obstruction of coronary artery disease (CAD) lesions. While visual estimation of %DS is widespread, because of high inter-operator variability, quantitative coronary arteriography (QCA) analysis is the gold standard. There are two %DS formulas: %DS1 averages the proximal and distal reference vessel diameter (RVD); %DS2 interpolates the RVD. This study aims to evaluate the difference between %DS assessed by QCA in two datasets, phantom lesion models and CAD patients. Ten phantom lesion models (PLMs) and 354 CAD lesions from the FIRST trial were assessed by QCA. In the latter, two scenarios were assessed: Scenario A (worst view), the most common approach in the clinical setting; and Scenario B (average of two complementary views), the standard core-laboratory analysis. In the PLMs, %DS1 and %DS2 mean ± standard deviation (median) was 58.5 ± 21.7 (61.6) and 58.7 ± 21.6 (61.8), respectively, with a signed difference of − 0.2% ± 0.3% (− 0.1%). In Scenario A, the mean %DS1 was 43.8 ± 9.1 (43.3) and 44.0 ± 9.1 (42 .9) in %DS2. In Scenario B, the mean %DS1 was 45.3 ± 8.8 (45.1) and 45.5 ± 9.0 (45.1) in %DS2. The signed difference was − 0.2% ± 2.4% (0.0%) and − 0.2% ± 2.1% (0.0%) in Scenario A and B, respectively. These differences between formulas ranged from − 1.2 to 0.5% for the phantom cases compared to − 17.7% to 7.7% in Scenario A and to − 15.5% to 7.1% in Scenario B. Although the overall means of the formulas provide similar results, significant lesion-level differences are observed. The use of the worst view versus the average of two views provided similar results. Subclinical left ventricular dysfunction assessed by two-dimensional speckle tracking echocardiography in asymptomatic patients with carotid stenosis Abstract The relationship between subclinical left ventricular (LV) dysfunction and atherosclerosis may have been underestimated in the past, which might be responsible for the high incidence of premature death in individuals with carotid stenosis. We sought to evaluate the underlying myocardial dysfunction in asymptomatic carotid stenosis patients using speckle tracking echocardiography (STE). Fifty patients with carotid stenosis ≥ 50% and a preserved LV ejection fraction (LVEF), and 45 controls without carotid stenosis who were matched in terms of vascular comorbidities were enrolled. All participants underwent carotid ultrasound and echocardiographic examination. The global LV longitudinal strain (GLS) was measured using STE. Compared with the control group, the e' of the mitral annular velocity and GLS were decreased in asymptomatic carotid stenosis patients (p < 0.05), however, the LVEF was well preserved. Based on a predefined cutoff for subclinical LV systolic dysfunction that was defined at a GLS < − 18%, this dysfunction was detected in 22 patients with carotid stenosis (44%) and in 10 patients in the control group (22%) (p < 0.05). The GLS was negatively correlated with the levels of low-density lipoprotein cholesterol (r = − 0.356, p < 0.05) and triglyceride (r = − 0.396, p < 0.05). In conclusion, LV diastolic and systolic functioning were significantly decreased in patients with asymptomatic carotid stenosis, and dyslipidemia likely contributed to the subclinical LV dysfunction in these patients. Our findings indicated the importance of detecting LV subclinical dysfunction and early intervention in this patient population. Conservative gadolinium administration to patients with Duchenne muscular dystrophy: decreasing exposure, cost, and time, without change in medical management Abstract Cardiac MR (CMR) is increasingly used to assess for cardiac involvement in patients with Duchenne muscular dystrophy (DMD). The frequent use of gadolinium based contrast agents (GBCAs) has been called into question with reports of intracranial gadolinium deposition in patients receiving multiple administrations. We adopted a conservative GBCA administration policy, limiting the frequency of GBCA exposure in patients with previously documented late gadolinium enhancement. The aim of our study was to evaluate the clinical effects of this policy change. Data were retrospectively reviewed on 405 consecutive patients with DMD who underwent CMR evaluation. Patients were grouped into conservative GBCA administration or historical control. CMR reports were evaluated and clinical reports were reviewed to determine actionable changes. Ohio Medicaid reimbursements were used to estimate costs. A total of 187 patients comprised the conservative GBCA group and 218 patients the historical cohort. The conservative GBCA group had lower contrast administration rates (84% vs. 99%, p < 0.0001), shorter scan times (35.2 vs. 39.0 min, p < 0.0001), and lower estimated medical costs ($339 vs. $351/study). There was no change regarding the initial presence of first-time late gadolinium enhancement, and no difference in actionable change. Contrast administration substantially decreased 7 months post-policy change (65%) compared to the initial 7 months (96%, p < 0.0001). In the current era with unclear concern for intracranial gadolinium deposition, thoughtful GBCA administration is warranted in patients anticipated to undergo multiple CMRs. Our updated approach has resulted in fewer patients receiving contrast, shorter scan times, and less medical costs, without appreciable changes to patient management.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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The Explanatory Role of Basic Psychological Need Experiences in the Relation between Dependency, Self-Criticism and Psychopathology in Adolescence Abstract According to Blatt's theory on personality development, adolescents with high levels of self-criticism and dependency are more vulnerable to diverse types of psychopathology. However, relatively little is known about intervening processes involved in this personality-based vulnerability. The goal of this study is to examine, on the basis of Self-Determination Theory, the explanatory role of the psychological needs for autonomy, competence, and relatedness in associations between self-criticism and dependency on the one hand and adolescents' internalizing and externalizing problems on the other hand. In this cross-sectional and multi-informant study, 284 adolescents (58,5% female; mean age = 14.15; SD = .93) and their parents reported about the adolescent's internalizing and externalizing problems. Adolescents also completed measures assessing self-criticism, dependency, and psychological needs experiences. Data were analyzed using structural equation modeling. Self-criticism and dependency were significantly related to higher levels of both internalizing and externalizing problems, with psychological need frustration fully mediating these associations. This study suggests that psychological need frustration is an important explanatory mechanism in personality-related vulnerability for adolescent psychopathology. More generally, it provides further evidence for the integration between two major theoretical approaches in the domain of adolescent development and psychopathology. Moderated Mediation of the Link between Parent-Adolescent Conflict and Adolescent Risk-Taking: the Role of Physiological Regulation and Hostile Behavior in an Experimentally Controlled Investigation Abstract Compared to childhood and adulthood, adolescence is a time of greater risk-taking behavior, potentially resulting in serious consequences. Theories of adolescent brain development highlight the imbalance between neural circuitry for reward vs. regulation. Although this imbalance may make adolescents more vulnerable to impaired decision-making in the context of heightened arousal, not all adolescents exhibit problematic risk behavior, suggesting other factors are involved. Relatedly, parent-adolescent conflict increases in mid-adolescence, and is linked to negative outcomes like substance use related risk-taking. However, the mechanism by which parent-adolescent conflict and risk-taking are linked is still unknown. Therefore, we investigated this association using a multi-method experimental design. Parent-adolescent dyads were randomly assigned to complete a discussion task together on the topic of either the adolescent's dream vacation or an adolescent-identified conflict topic. During the task, adolescent peripheral psychophysiology was measured for later calculation of heart rate variability (HRV), an index of self-regulation. Immediately after the discussion task, adolescents completed a performance-based measure of risk-taking propensity that indexes real-world risk behaviors. We hypothesized that parent-adolescent conflict would predict greater adolescent risk-taking propensity, and that increased behavioral arousal in the context of conflict, coupled with impaired self-regulation, would explain this link. Results indicated no direct effect of parent-adolescent conflict on adolescent risk-taking propensity. However, there was a significant conditional indirect effect: lower HRV, indexing worse regulatory ability, mediated the relation between conflict and risk-taking propensity but only for adolescents exhibiting behavioral arousal during the discussion task. We discuss implications for understanding adolescent risk-taking behavior. Cognitive Styles in Preschool-Age Children: Associations with Depression Risk and Evidence of Stability Abstract Evidence suggests cognitive styles are associated with depression; however, little research has examined cognitive styles in early childhood. Using developmentally appropriate, stress-inducing laboratory paradigms to assess young children's cognitive vulnerability, the current study assessed negative and positive cognitive styles, their concurrent associations with well-established risk factors for depression in early childhood, and their stability from early to middle childhood. Participants included 173 preschool-aged children and their parents. Cognitive styles were assessed by coding children's negative and positive self-referent and non-self-referent verbalizations and assistance-seeking verbalizations during stress-inducing laboratory tasks during early childhood (Wave 1; ages 3–5) and middle childhood (Wave 2; ages 6–10). Children's Wave 1 verbalizations were concurrently associated with exposure to maternal depression, child negative and positive temperamental emotionality, and child externalizing psychopathology. Assistance-seeking verbalizations demonstrated homotypic continuity from Wave 1 to Wave 2, and both assistance-seeking verbalizations and negative non-self-referent verbalizations at Wave 1 predicted increases in negative self-referent verbalizations from Wave 1 to Wave 2. Findings suggest that cognitive styles can be observed in young children when using an ecologically valid assessment and are linked to risk factors for depression. Further research is warranted to elucidate the development of cognitive vulnerability in young children, which may inform prevention and early interventions targeting cognitive risk for depression. Emotion Sensitivity of the Error-Related Negativity in Hoarding Individuals Abstract Emerging research suggests that hoarding individuals display atypical activation in their anterior cingulate cortex (ACC). Hemodynamic studies have found a biphasic pattern of ACC activity in hoarding individuals that appears sensitive to possession-related decision-making. Electrophysiological studies suggest that hoarding individuals display a blunted error-related negativity (ERN); an event-related potential originating from the ACC that indexes error-detection. These neural abnormalities may reflect an error sensitivity in hoarding individuals as they acquire and discard, however it may also reflect the hyper-emotionality often reported by individuals who hoard. The present study aimed to examine the emotional sensitivity of the error-related negativity in hoarding individuals outside a possession-related context. Seventeen hoarding individuals and 16 healthy controls underwent continuous electroencephalography (EEG) as they completed Go/No-Go (GNGT) tasks design to elicit the ERN. Identical GNGT tasks were completed both before and after watching a negative mood induction video, and self-reported distress was measured throughout. Neither group displayed any neural effect of the negative mood induction, however the hoarding group displayed a pattern of blunted ERN consistent with previous research. This study provides additional evidence that hoarding individuals display blunted indices of error-detection outside possession-related decision-making. Future research could explore if this reflects a pathophysiology shared with other psychiatric disorders that feature a blunted ERN, and if error-detection is also abnormal as hoarding individuals acquire and discard their possessions. A Psychometric Evaluation of the Revised Childhood Anxiety Sensitivity Index (CASI-R) in a Child and Adolescent Sample Abstract The multifactorial nature of anxiety sensitivity (AS) in children has been assessed almost solely with the Childhood Anxiety Sensitivity Index (CASI; Silverman et al. Journal of Clinical Child Psychology, 20(2), 162–168, 1991); however, multiple studies have suggested that the item content of the CASI is too limited to adequately assess multiple AS factors in youth. Here we examined the psychometric properties of the Revised Childhood Anxiety Sensitivity Index (CASI-R; Muris Behaviour Research and Therapy, 40, 299–311, 2002), developed to assess a higher-order global AS factor and four lower-order factors. In a non-clinical sample of youth aged 8–14 we (a) examined the psychometric properties of the CASI-R, comparing findings for children aged 11 and younger with those aged 12 and older, (b) evaluated and compared the internal consistency of the four-factor CASI-R and the three- and four-factor CASI, and (c) examined and compared the convergent validity of the CASI and CASI-R subscales with child-reported anxiety symptoms. Reliability estimates for the CASI-R total, Cardiovascular, and Respiratory scales were high for all youth; the Cognitive Dyscontrol and Publicly Observable Reactions scales yielded low estimates of internal consistency for the younger group. Compared to the parallel CASI scales, these CASI-R scales demonstrated stronger internal consistency in both the older and younger groups. Comparatively larger correlations between the CASI-R physical and cognitive scales with symptoms of panic and between the CASI-R social scale and symptoms of social anxiety were observed. These findings suggest continued use and examination of the CASI-R in child and adolescent non-clinical and clinical samples to comprehensively assess the AS construct in youth. Differences and Similarities in how Psychopathic Traits Predict Attachment Insecurity in Females and Males Abstract We examined whether there are differential associations between latent psychopathy (Interpersonal, Affective, Lifestyle, Antisocial) and adult attachment anxiety and avoidance factors, and if sex moderated the associations in a large sample of young adults (n = 590). Participants completed the Self-Report Psychopathy-Short Form (SRP-SF) and the Experiences in Close Relationships (ECR) attachment scale. Based on norms from the SRP Manual (Paulhus et al. 2017), 19.1% reported an elevated SRP total score (T-score = 60). Multiple group structural equation modeling (MGSEM) was conducted with item factor loadings and thresholds constrained to be equal across male and female subsamples. The MGSEM results indicated excellent model fit (CFI = .95; RMSEA = .04), thus providing evidence of strong invariance and assurance of equvalence of measurement across sex. The pattern of SEM results across males and females revealed both similar and differential relations between specific psychopathy and attachment factors. For both sexes, the Affective psychopathy factor had a significant effect on Avoidant attachment (Males, β = .48; Females, β = .48). In contrast, for males, the Avoidant attachment factor was linked with the Lifestyle factor (β = .47), while for females, the Antisocial factor had a negative effect on Avoidant attachment (β = −.23). The findings highlight both similarities and differences across sex regarding the associations between psychopathic trait domains and disturbances in adult attachment consistent with previous studies. Discussion of this pattern of results and their implications for further understanding of psychopathic traits in males versus females are provided. Distinguishing SCT Symptoms from ADHD in Children: Internal and External Validity in Turkish Culture Abstract In this study, our aim was to evaluate the internal and external validity of Sluggish Cognitive Tempo (SCT) and to determine if it is an independent factor from Attention Deficit Hyperactivity Disorder (ADHD) in Turkish children, like in other cultures. Two hundred sixty-one children (6–12 years of age) who applied to Ankara University Child and Adolescent Psychiatry outpatient clinics and diagnosed with ADHD recruited the study. All children were evaluated with the Schedule for Affective Disorders and Schizophrenia for School-Age Children Present and Lifetime Version which is a semi-structured diagnostic interview (K-SADS-PL) for ADHD diagnosis. Child Behavior Checklist for ages 6–18, The Barkley's Child SCT Ratings Scale, SNAP-IV Parent and Teacher Scale, and Sociodemographic Information Form were enrolled by the parents and teachers of the children. Our results demonstrated that SCT symptoms formed two distinct but interrelated factors (Sluggish and Daydreaming) separate from those for ADHD. Due to regression analyses, higher levels of SCT predicted higher levels of ADHD-IN (Inattentive) and internalizing symptoms including anxiety-depression, social problems, and social withdrawal. These findings distinguished SCT cases from ADHD-IN in Turkish children. Results also indicated that ADHD- IN symptoms are risk factors for lower academic achievement while SCT symptoms haven't such an effect. Our study is the first which demonstrates SCT's construct validity relative to ADHD-IN by parental and teacher ratings in Turkey. Similar findings with Turkish children to the findings with children from other cultures would increase our confidence in the transcultural generalizability of SCT's internal-external validity. Interrelations among Biologically Relevant Personality Traits, Emotion Regulation Strategies, and Clinical Symptoms Abstract Biologically relevant personality traits of weak inhibitory control (disinhibition) and threat sensitivity confer vulnerability to various clinical problems. Difficulties with emotion regulation have also been studied extensively in relation to risk for and maintenance of psychopathology. However, it remains unclear how emotion regulation strategies interface with dispositional vulnerabilities in affecting clinical symptomatology. The current study provided an initial examination of the roles of disinhibition, threat sensitivity, and use of key emotion regulation strategies (cognitive reappraisal, expressive suppression) in the occurrence of distress-related symptoms (i.e., depressivity, anxiousness, and borderline personality features). Analyses revealed that trait disinhibition and lowered use of cognitive reappraisal were related to each form of distress symptomatology, with the predictive relationship for disinhibition accounting entirely for that of reappraisal. This finding suggests that deficient top-down control capacity (i.e., disinhibition) is integral to failures in the use of an adaptive but cognitively demanding regulation strategy (i.e., reappraisal). By contrast, threat sensitivity was related both to anxiousness and use of expressive suppression, with the latter two variables unrelated to one another. Anxious individuals may avoid emotionally evocative situations, negating the downstream need to engage in the maladaptive strategy of expressive suppression. Despite certain study limitations (a cross-sectional, self-report design; modest sample size), the current study yielded evidence in line with study hypotheses, indicating a pivotal role for dispositional traits in associations between cognitive-behavioral processes and clinical problems. Motives for Nonsuicidal Self-Injury in Individuals with Lifetime Depressive Disorders and Posttraumatic Stress Disorder Abstract Although researchers have identified a number of factors that may motivate individuals to engage in nonsuicidal self-injury (NSSI), few studies have examined whether motives for NSSI differ as a function of psychiatric diagnosis. Therefore, the goal of the present study was to examine motives for lifetime NSSI among individuals with a history of psychiatric disorders associated with elevated rates of NSSI: depressive disorders and posttraumatic stress disorder (PTSD). Young adults (N = 139) with a history of NSSI completed several diagnostic interviews and questionnaires, including a measure of lifetime NSSI motives. Results demonstrated that participants with (vs. without) a lifetime depressive disorder reported significantly lower levels of interpersonal influence motives for NSSI, and participants with (vs. without) lifetime PTSD reported significantly higher levels of emotional relief and feeling generation motives. Further, results revealed a significant interaction between lifetime depressive disorders and PTSD for interpersonal communication motives; specifically, whereas participants with lifetime diagnoses of both a depressive disorder and PTSD did not differ significantly in reported interpersonal communication motives from participants with neither diagnosis, those with lifetime PTSD but without a lifetime depressive disorder reported significantly higher levels of interpersonal communication motives than those without either diagnosis. Results suggest that a history of depression and PTSD (alone and in combination) may be associated with different motives for NSSI. Schizotypy from the Perspective of the DSM-5 Alternative Model of Personality Traits: a Study on a Sample of 1056 Italian Adult University Students Abstract To assess the relationships between schizotypy measures and DSM-5 Alternative Model of Personality Disorders (AMPD) traits, 1056 (69.4% female; mean age = 23.30 years) University students, were administered the Italian translation of the Schizotypal Personality Questionnaire (SPQ), Schizotypal Personality Scale (STA), Schizotypy Scale (SS), and Personality Inventory for DSM-5 (PID-5). Exploratory structural equation modeling (ESEM) suggested that the SPQ, STA, and SS Schizofrenism scale total scores may represent primary measures of schizotypy/Schizotypal personality disorder (PD), whereas the SS anhedonia (AH) total score represent an index of the general anhedonia level. MAMBAC, MAXCOV, and LMode taxometric analyses showed that both schizotypy and anhedonia constructs had a dimensional distribution (all comparison curve fit index values<.40). Bayesian confirmatory factor analysis (CFA) supported a two-factor model of SPQ, STA, SS SZ and SS AH scale total scores. Hierarchical regression analyses showed that DSM-5 AMPD traits that were hypothesized to define the Schizotypal PD profile (i.e., Cognitive and Perceptual Dysregulation, Unusual Beliefs and Experiences, Eccentricity, Restricted Affectivity, Withdrawal, and Suspiciousness), as well as the additional specifiers (i.e., Anxiousness, and Depressivity) explained 66.0% of the systematic variance in the schizotypy factor scale scores. Our findings suggested that schizotypy could be represented as a continuously-distributed latent variable which may be effectively described in terms of a coherent system of dysfunctional personality traits.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Public Solicitation and The Canadian Media: Two Cases of Living Liver Donation, Two Different Stories Background . Two stories of public solicitation for living liver donors received substantial Canadian media attention in 2015: The Wagner family, with twin toddlers, each needing transplants, and Eugene Melnyk, wealthy owner of a professional hockey team. This study compared the print media coverage of these 2 stories to understand how public solicitation was portrayed and whether coverage differed depending on the individual making the plea. Methods. We conducted a content analysis on 155 relevant Canadian newspaper articles published between January 1, 2015 and December 31, 2016. Articles were analyzed for their description of public solicitation, benefits and issues associated with public solicitation, and overall tone with respect to public solicitation. Results. The foregrounding of public solicitation and associated ethical issues featured heavily in articles focused on Melnyk but were largely absent when discussing the Wagner family. The fairness of Melnyk's solicitation was the most prominent ethical issue raised. Laws and policies surrounding public solicitation also featured in the Melnyk story but not in articles focused on the Wagners. Public solicitation was portrayed more negatively in the Melnyk articles, but overall, was portrayed positively in relation to both Melnyk and the Wagner family. Conclusions. Public solicitation was generally portrayed as a positive phenomenon in Canadian print media, yet there were stark differences in how these cases were presented. The Wagner story was largely portrayed as a human-interest piece about a family in dire circumstances, whereas Melnyk's wealth, status, and influence raised questions of the fairness of his transplant. Published online 15 November, 2019. Received 4 September 2019. Revision received 18 September 2019. Accepted 19 September 2019. Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.transplantationdirect.com). Supported by Genome Canada and Genome Alberta: Precision Medicine Applying Precision Medicine Technologies in Canada to Prevent Antibody Mediated Rejection and Premature Kidney Transplant Loss (CanPREVENT AMR) and Canadian Institutes of Health Research and the Kidney Foundation of Canada: The Canadian National Transplant Research Program: Increasing Donation and Improving Transplantation Outcomes. A.R.M., M.T., T.C. designed the study. A.R.M. compiled and analyzed the data with assistance from M.T., A.R.M., and M.T. wrote the initial drafts of the article. A.R.M., M.T., and T.C. edited, revised, and contributed to the final version of the article. The authors declare no conflicts of interest. Correspondence: Maeghan Toews, LLM, Adelaide Law School Room 2.05 Ligertwood Bldg University of Adelaide, N Trc Adelaide SA 5005, Australia. (maeghan.toews@adelaide.edu.au). This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. © 2019 The Authors. Published by Wolters Kluwer Health, Inc. Whole Body CT Imaging in Deceased Donor Screening for Malignancies Background. In most western countries, the median donor age is increasing. The incidence of malignancies in older populations is increasing as well. To prevent donor-derived malignancies we evaluated radiologic donor screening in a retrospective donor cohort. Methods. This study analyzes the efficacy of a preoperative computed tomography (CT) scan on detecting malignancies. All deceased organ donors in the Netherlands between January 2013 and December 2017 were included. Donor reports were analyzed to identify malignancies detected before or during organ procurement. Findings between donor screening with or without CT-scan were compared. Results. Chest or abdominal CT-scans were performed in 17% and 18% of the 1644 reported donors respectively. Screening by chest CT-scan versus radiograph resulted in 1.5% and 0.0% detected thoracic malignancies respectively. During procurement no thoracic malignancies were found in patients screened by chest CT compared with 0.2% malignancies in the radiograph group. Screening by abdominal CT-scan resulted in 0.0% malignancies, compared with 0.2% in the abdominal ultrasound group. During procurement 1.0% and 1.3% malignancies were found in the abdominal CT-scan and ultrasound groups, respectively. Conclusions. Screening by CT-scan decreased the perioperative detection of tumors by 30%. A preoperative CT-scan may be helpful by providing additional information on (aberrant) anatomy to the procuring or transplanting surgeon. In conclusion, donor screening by CT-scan could decrease the risk of donor-derived malignancies and prevents unnecessary procurements per year in the Netherlands. Published online 15 November, 2019. Received 5 September 2019. Accepted 29 September 2019. The authors declare no funding or conflicts of interest. Author contributions A.E.B., I.P.J.A., and J.W.M. participated in research design. J.W.M. participated in data collection. A.E.B., R.A.P., and J.W.M. participated in data analysis. All authors participated in construction and critical revision of the article. Correspondence: J.W. Mensink, MD, Department of Surgery, Division of Transplantation, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. (j.w.mensink@hotmail.com). This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. © 2019 The Authors. Published by Wolters Kluwer Health, Inc. Comparison of a Behavioral Versus an Educational Weight Management Intervention After Renal Transplantation: A Randomized Controlled Trial Background. In the first year following renal transplantation, preventing weight gain to minimize overweight or obesity is particularly important. The aim of this study is to test the effect of an 8-month behavioral intervention BMI and physical activity. Methods. This randomized controlled study included 123 adult kidney or kidney-pancreas recipients. Patients were randomized to usual (1 educational session, then weight self-monitoring) and intervention care (usual care plus 7–8 counseling sessions). Alongside weight, body composition, and physical activity, satisfaction and perceptions regarding care were measured at weeks 2–6 (baseline), then at months 8 and 12. Results. Both groups reported comparably high satisfaction. The intervention group (IG) reported more chronic care-related activities. In patients with BMIs ≥ 18.5, mean weight gain (from baseline) was unexpectedly low in both groups: at month 8, +0.04 kg/m2 in IG patients and +0.14 kg/m2 in the control group (P = 0.590), and respectively, +0.03 kg/m2 and +0.19 kg/m2 at month 12 (P = 0.454). Both groups were physically active, walking averages of 10 807 (IG) and 11 093 (control group) steps per day at month 8 (P = 0.823), and respectively 9773 and 11 217 at month 12 (P = 0.195). Conclusions. The behavioral intervention had high patient acceptance and supported patients in maintaining their weight, but had no superior effect on a single educational session. Further research is needed to assess patient weight gain risk profiles to stratify the intervention. Published online 15 November, 2019. Received 5 July 2019. Accepted 26 July 2019. Trial registration number: NCT02282124 (ClinicalTrials.gov) G.S-M. performed the writing of the article, designing the study, and study management. P.Z. performed the co-writing of the article and development and provision of the intervention. N.G. performed the co-writing of the article and statistical analysis. P.W. performed the co-designing and implementation of intervention in clinical practice and critical revision of article. T.F.M. performed the critical revision of article R.W. performed the implementation of study in clinical practice. L.H. performed the data management. T.F. is the second senior author and performed the co-designing of the study and intervention and critical revision of article. R.S. performed the co-designing of the study and the intervention and critical revision of article. T.F. and R.S. are both senior author. The authors declare no conflicts of interest. Supported by an unrestricted grant from Astellas Pharma Switzerland, Novartis Pharma Switzerland, and the Béatrice Ederer-Weber Stiftung Switzerland. Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.transplantationdirect.com). Correspondence: Gabriela Schmid-Mohler, PhD, RN, Center of Clinical Nursing Science, University Hospital Zurich, Ramistrasse 100, CH-8091 Zurich, Switzerland. (gabriela.schmid@usz.ch). This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. © 2019 The Authors. Published by Wolters Kluwer Health, Inc. Insights Into the Experience of Liver Transplant Recipients With Alcoholic Liver Disease: A Descriptive Qualitative Study Background. Alcoholic liver disease (ALD) due to alcohol use disorder (AUD) is the primary cause of liver transplantation (LT) in the United States. Studies have found that LT recipients experience a range of physical and emotional difficulties posttransplantation including return to alcohol use, depression, and anxiety. The aim of this study is to better understand the experiences of LT recipients with ALD because they recovered posttransplant to inform the development of a patient-centered intervention to assist patients during recovery. Methods. Using qualitative methods, researchers conducted semi-structured interviews with 16 ALD LT recipients. The primary topics of the interview were physical recovery, mental health, substance use including alcohol and tobacco use, and financial experiences. Common patient themes were identified and coded. Results. Within the domain of physical health, patients stressed that undergoing LT was a near-death experience, they were helpless, changes in weight influenced their perception of their illness, and they have ongoing medical problems. In the domain of mental health, patients described cognitive impairments during their initial recovery, difficulty in processing the emotions of having a terminal condition, ongoing depression, anxiety, and irritability. The patients also described their perception of having AUD, the last time they used alcohol and their attitude to AUD treatment posttransplant. Patients also described their reliance on one member of their social support network for practical assistance during their recovery and identified one member of their medical team as being of particular importance in providing emotional as well as medical support during recovery. Conclusions. The patient's description of their lived experience during the months following transplant informed the development of a patient-centered intervention that colocates behavioral health components with medical treatment that helps broaden their social network while addressing topics that emerged from this study. Published online 15 November, 2019. Received 29 January 2019. Revision received 20 September 2019. Accepted 21 September 2019. The authors declare no conflicts of interest. This work was supported by Agency for Healthcare Research and Quality #5R24HS022135-04/PI. M.H. conducted interviews and participated in creating coding scheme, coding transcripts, and writing the preliminary draft of the article. M.L.M. participated in research design and creating coding scheme, conducted interviews, participated in coding transcripts, and contributed to major editing of the draft. M.T. and J.L.M. and M.C. participated in research design, reviewed coding scheme, and reviewed and edited the article. P.S. conceptualized the study and provided oversight of research design, participated in creating coding scheme and writing preliminary draft of the article, and reviewed and substantially edited the final article. Correspondence: Martin Hochheimer, MSW, University of Maryland School of Social Work, 525 W Redwood St, Baltimore, MD 21201. (mhochheimer@ssw.umaryland.edu). This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. © 2019 The Authors. Published by Wolters Kluwer Health, Inc. Evaluation of Intrahepatic Lactate/Pyruvate Ratio As a Marker for Ischemic Complications Early After Liver Transplantation—A Clinical Study Background. Lactate/pyruvate ratio has been introduced as a sensitive marker for ischemia in the transplanted liver. In the present study, we aimed to evaluate lactate/pyruvate ratio measured in the liver by microdialysis as a marker for ischemic complications early after liver transplantation. Methods. Forty-five patients undergoing liver transplantation were included in the study. A microdialysis catheter was placed in the liver graft directly following liver transplantation and the metabolites lactate and pyruvate measured for up to 6 days and the lactate/pyruvate ratio calculated. The association between increased intrahepatic lactate/pyruvate ratio and ischemic complications was studied. Results. One of 45 patients developed hepatic arterial thrombosis. Forty-four events with increased lactate/pyruvate ratio were identified in 24 patients. In none of the 24 patients that had a raised lactate/pyruvate ratio could we detect occurrence of any ischemic complication. In the patient that did have hepatic arterial thrombosis, the lactate/pyruvate ratio did not show a significant prolonged rise. Conclusions. An increase in the intrahepatic lactate/pyruvate ratio is not necessarily indicative of ischemic complications and is thus not a reliable marker for monitoring of clinically significant ischemia in the liver early after transplantation. Published online 15 November, 2019. Received 7 June 2016. Revision received 16 September 2019. Accepted 25 September 2019. A.v.P. involved in collection and analyzing of data and writing article. M.A.D.S. involved in analyzing of data and writing article. O.R. involved in writing article. G.N. involved in study design, collection and analyzing of data, and writing article This work was supported by CMA Microdialysis AB, Stockholm, Sweden. Pregraduate School of Clinical Science, Karolinska Institute. The authors declare no conflicts of interest. Correspondence: Anna von Platen, MD, Division of Transplantation Surgery, CLINTEC, Karolinska Institute, Karolinska University Hospital Huddinge F82, 141 86 Stockholm, Sweden. (annavonplaten@sll.se). This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. © 2019 The Authors. Published by Wolters Kluwer Health, Inc.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Water Quality Assessment and Variation Trends Analysis of the Min River Sea-Entry Section, China Abstract In order to further understand the status of the water quality of Min River's sea-entry section, the index systems for water environmental quality assessment was built based on twenty evaluation parameters including dissolved oxygen (DO), permanganate index (CODMn), chemical oxygen demand (CODCr), biochemical oxygen demand (BOD5), ammonia (NH3-N), total phosphorus (TP), and total nitrogen (TN). Water environmental quality of Min River's sea-entry section in 2015–2017 was evaluated by utilizing the entire-array-polygon synthesis illustration method, accompanied by the time-dependent trend analysis. The results demonstrated that the water environmental quality of Min River's sea-entry section was between the levels I and II of the Environmental Quality Standards for Surface Water (EQSSW, GB3838-2002) in 2015–2017, indicating a generally good water quality. The water quality was affected by both natural factors (such as temperature, rainfall, and runoff) and human factors and had a tendency to deteriorate at the duration of 2015–2017. The research results are of great significance for further understanding of the discharge of pollutants from the Min River basin and will be a strong support for the scientific decision-making of marine management in Fujian Province. Influence of Heavy Metals on Seed Germination and Seedling Growth of Wheat, Pea, and Tomato Abstract Experiments were conducted under lead (Pb), cadmium (Cd), and copper (Cu) exposure to observe germination and seedling growth of wheat (Triticum aestivum L), pea (Pisum sativum), and tomato (Solanum lycopersicum L.). Metals were applied in five concentrations (20, 65, 110, 175, and 220 ppm) and Hoagland solution was used to feed the seedlings. Irrespective of the tested crop seeds, copper revealed maximum effect (51.2%) on germination followed by lead (47.5%) and cadmium (35.3%). Tomato seeds were most sensitive in germination stage followed by pea and wheat. In seedling stage, tomato also showed highest sensitivity to both Cd and Cu. However, pea seedlings showed higher tolerance to Pb and wheat seedlings had the highest tolerance to both Cu and Cd. Toxicity and tolerance of metals was found to vary with crops and growth stages. Higher transfer of metals (Pb, Cd, and Cu) in wheat seedling indicates higher risk of food chain contamination when grown in polluted soil. Higher mobility and uptake of Cd in tomato and wheat seedlings even under lower concentration of exposure needs further study. Paracetamol Degradation Performance and Mechanisms Using Microwave-Assisted Heat-Activated Persulfate in Solutions Abstract A microwave (MW) heat-activated the persulfate (PS) process was employed to treat paracetamol (PAM) in wastewater, and the powder-activated carbon (PAC) be used is used as a catalyst to accelerate this reaction process. The PAM added (100 mg) to the solution was nearly completely removed within 70 min, and the PH, temperature, PAC, and PS dosage have great influence on the degradation process; the total organic carbon (TOC) removal rate reached 98%. The PAC1 still had a good catalytic effect after being reused six times. The radical mechanism was investigated to determine the type of dominant active species involved in PAM degradation. Sulfate radicals ($ {\mathrm{SO}}_4^{-\bullet } $) were the dominant oxidizing agent for PAM degradation under acidic conditions. The degradation mechanism was proposed based on the PAM degradation intermediates, which were identified using ultra-high-performance liquid chromatography coupled with linear trap quadrupole orbitrap mass spectrometry. Three types of possible reaction pathways for PAM were identified as follows: including hydroxylation of the benzene ring, amine group oxidation at the benzene ring, and amine (HN–C=O) functional group N–C bond cleavage. A Chemical Time Bomb: Future Risks of Microplastics Abstract Despite the controversy, the ecological risk of microplastics research has increased sharply from only one in 1966 to 495 in 2018, according to Web of Science with microplastics as keyword. To date, an upward trend of global microplastics mass emission was confirmed by many environmental scientists. The ocean is the ultimate destination of land-based microplastics sources; therefore, most of efforts were concentrated on microplastics in aquatic environment. In this brief article, the global release of microplastics and flux into the ocean in the recent decade were estimated roughly. The plastics fragmentation in the marine environment only accounted for 22% of total microplastics release (assuming defined emission rate per capita and fragmentation rate of plastics). Future research is needed for microplastics generation and retention in the terrestrial system, especially indoor environments. The accumulated microplastics over the environmental self-purification capacity certainly increases stress for the marine, freshwater and terrestrial ecosystem. The Effect of Temperature Oscillations and Sediment Texture on Fecal Indicator Bacteria Survival in Sediments Abstract Fecal indicator bacteria (FIB) inhabiting stream sediments have become a concern with regard to recreational and irrigation water quality. Sediments contain higher concentrations of E. coli and other FIB than the overlying water column. The objective of this work was to evaluate the effect of temperature oscillations on the populations of both E. coli and enterococci in sediments and the water column. The study was conducted in a microcosm system with flow-through chambers representing a small stream with two different sediment textures. Bovine manure was freshly collected and mixed with both clayey and sandy sediment. Temperatures within the chambers oscillated from 17° to 28 °C which is representative of a diurnal summer temperature range for Maryland; the control chambers were kept at 22 °C. The effect of temperature oscillations differed depending on the sediment texture. Bacterial populations in the sandy sediment immediately increased before net die-off began. Conversely, in the chambers with the clayey sediments, there was no immediate increase in concentrations in the oscillation chambers as compared to the controls. There were significantly higher populations of both E. coli and enterococci within the oscillation sandy texture chambers compared to the control constant temperature chambers; that was not the case in the clayey sediment chambers. The die-off rates in the sandy sediments were greater than those in the clayey sediments; in the latter, bacteria populations remained almost constant throughout the experiment. Temperature oscillations should be simulated in experiments designed to estimate and compare inactivation rates for fecal indicator bacteria in sediments for future inferences on microbial water quality. Spatial and Temporal Evolution Characteristics of Drought in Yunnan Province from 1969 to 2018 Based on SPI/SPEI Abstract The objective of this article is to describe the effect of precipitation and temperature on the drought characteristics of Yunnan province in China. The rainfall and temperature data from 10 national meteorological stations in Yunnan province during 1969 to 2018 were used to investigate the spatial and temporal evolution of drought in Yunnan province and the difference of drought index based on Standardized Precipitation Index (SPI) and Standardized Precipitation Evapotranspiration Index (SPEI) at nearly 50a different time scales. The results showed that Yunnan province had a frequent alternation of drought and flood, and the larger the time scale, the gentler the SPI and SPEI changes. The recent 50a drought mainly occurred in 1980–1982, 1988–1990, 2003–2007, and 2010–2015, and there was continuous drought and the duration was prolonged. The changes of SPI and SPEI showed a downward trend in different seasons. The linear slopes of SPI and SPEI in spring, summer, autumn, and winter were − 0.0064, − 0.0088, − 0.0057 and − 0.0.0111, respectively, and the drought trend was the most serious in winter. Continuous spring drought occurred in 2009–2010 and 2012–2014. The SPEI values in 2009–2010 and 2012–2014 were − 0.80, − 0.64, − 0.75, − 1.23, and − 1.17, respectively. The spatial distribution of drought frequency in Yunnan province was greatly different, and its distribution rule was more in the north and east, less in the south and west. The drought frequency in Zhaotong (northeast Yunnan) was the highest at 36.53%, the drought frequency in Deqin and Lijiang (northwest Yunnan) were 33.11% and 33.28%, and the drought frequency in Kunming (central Yunnan) Lincang, Lancang, and Simao (southwest Yunnan) were 29.35%, 30.73%, 32.77%, and 28.35%, respectively. This study provided a scientific basis for revealing the spatial and temporal variation rules, evolution trends, regional drought, and drought impact assessment and risk management of drought in Yunnan province. Soil Heavy Metal(loid) Pollution and Phytoremediation Potential of Native Plants on a Former Gold Mine in Ghana Abstract This study investigated the soil pollution level and evaluated the phytoremediation potential of 25 native plant species on a former gold mine-tailing site in Ghana. Plant shoots and associated soil samples were collected from a tailing deposition site and analyzed for total element concentration of As, Hg, Pb, and Cu. Soil metal(loid) content, bioaccumulation factor (BAFshoots), and hyperaccumulator thresholds were also determined to assess the current soil pollution level and phytoextraction potential. The concentration of As and Hg in the soil was above international risk thresholds, while that of Pb and Cu were below those thresholds. None of the investigated plant species reached absolute hyperaccumulator standard concentrations. Bioavailability of sampled metal(loid)s in the soil was generally low due to high pH, organic matter, and clay content. However, for Cu, relatively high bioaccumulation values (BAFshoots > 1) were found for 12 plant species, indicating the potential for selective heavy-metal extraction via phytoremediation by those plants. The high levels of As at the study site constitute an environmental and health risk but there is the potential for phytoextraction of Cu (e.g., Aspilia africana) and reclamation by afforestation using Leucaena leucocephala and Senna siamea. Role of AM Fungi in the Uptake and Accumulation of Cd and Ni by Luffa aegyptiaca Abstract Sponge gourd (Luffa aegyptiaca) was grown in pots with and without inoculation with two arbuscular mycorrhizal (AM) fungi, viz., Glomus macrocarpum and Glomus monosporum singly and in combination. Seven-day-old plants were treated with 18.9 μg Cd g−1 soil and 155.4 μg Ni g−1 soil alone and in combination. At 90 days old stage, dry weight of root, shoot, and fruit; uptake of heavy metals in root, stem, leaves, and fruits; percent mycorrhizal root colonization; and spore number in the root zone were determined. When applied singly, the uptake of Cd and Ni in host plants was enhanced more effectively by G. monosporum than G. macrocarpum. The larger proportion of Cd uptake in uninoculated host was retained in the roots but in inoculated plants (with both Glomus sp.), major amounts of the Cd were translocated to the above ground parts including fruits. The leaves were the main sinks of Ni in inoculated plants. The overall tissue burden of both heavy metals in the host was enhanced relatively more effectively on association with G. monosporum as compared with G. macrocarpum. The uptake of Cd was relatively higher in plants treated with both the metals and both the AM fungi. Despite the relatively higher uptake of both the heavy metals in inoculated plants, the host dry weight was significantly higher compared with uninoculated plants. The percent mycorrhizal root colonization of the host by both AM fungi was higher in plants grown without either of the heavy metals. The combined application of both the heavy metals reduced the spore density in the root zone soil of host. The results show that the AM fungi enhanced the uptake of Cd and Ni by the host but alleviated the toxicity by promoting plant growth. The Azo Dye Degradation and Differences Between the Two Anodes on the Microbial Community in a Double-Anode Microbial Fuel Cell Abstract The anode configuration determined the performance of power generation and contaminant removal in microbial fuel cell (MFC). In this study, double anodes were constructed along an up-flow MFC for mitigating the suppression of refractory organic azo dye Reactive Brilliant Red X-3B and increasing the power output. Results revealed that high concentration of X-3B suppressed the power generation of MFC. The maximum power density decreased from 0.413 to 0.161 W/m3, and the inner resistance rose from 448 to 698 Ω. However, double anodes weakened the suppression of X-3B to the current generation. Compared with single anode, the attenuation of MFC current decreased from 48 to 40%. Meanwhile, the X-3B removal efficiency in double-anode MFC was 19.81% higher compared with a single-anode condition when the X-3B was 1000 mg/L. The degradation pathway analysis indicated that aromatic amines formation and further oxidation were achieved sequentially in the MFC. Furthermore, microbial communities in the lower and upper anodes were analyzed, revealing that the microorganisms in the lower anode were more inclined to degrade the pollutant, whereas those in the upper anode were more inclined to generate electricity. This double-anode structure showed the potential for large concentration range of azo dye removal and the current recovery in real textile wastewater. Removal of Cu and Zn from Aqueous Solutions by Selected Tree Leaves with Phytoremediation Potential Abstract In this study, some different selected plant leaves grown in Jordan such as Citrus limon (Rutaceae), Ceratonia siliqua L., Olea europaea (Oleaceae), Washingtonia filifera, and Myoporum (Myoporaceae) were examined for removal of copper (Cu) and zinc (Zn) ions from aqueous solutions. Cu and Zn were analyzed by atomic absorption spectrometry. A pH S-2 acidometer was used for determining the acidity of leaves solution system. Our findings showed the plants leaves were relatively efficient for removal of Cu and Zn compared to activated carbon. Removal of a 5 mg/L aqueous metal solution of Cu and Zn was treated with 2.5 g oven-dried plant in a 50 mL deionized water. The removal of Cu and Zn was expressed in terms of a time function ranged between 0 and 192 hours of contact time. The uptake of Cu and Zn by plant leaves was arranged in the following order: Cu: Activated carbon > Washingtonia filifera > Ceratonia siliqua L. > Olea europaea (Oleaceae) > Myoporum (Myoporaceae) > Citrus limon (Rutaceae) Zn: Activated carbon > Olea europaea (Oleaceae) > Citrus limon (Rutaceae) > Ceratonia siliqua L. > Washingtonia filifera > Myoporum (Myoporaceae)

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Julia Dahlvik (2018): Inside Asylum Bureaucracy: Organizing Refugee Status Determination in Austria Mayer, Stefanie (2018): Politik der Differenzen. Ethnisierung, Rassismen und Antirassismus im weißen feministischen Aktivismus in Wien Zwischen Statuskrise und Autonomiebegehren: Solo-Selbstständigkeit als generationstypische Bearbeitung des Wandels von Arbeit und Biografie Zusammenfassung Der vorliegende Beitrag untersucht soloselbstständige Erwerbstätigkeit aus einer biografieanalytischen und generationalen Perspektive. Anhand einer Einzelfallanalyse wird nachgezeichnet, welche Anforderungen an die biografische Selbstgestaltung die Solo-Selbstständigkeit als individualisiertes Muster der Lebensführung stellt. Die Frage nach den Möglichkeiten und Normierungen des biografischen Handelns führt in einem weiteren Analyseschritt zu einer Betrachtung des Generationszusammenhangs der Interviewten, dem Milieu der akademischen Kulturberufe sowie dem marktlichen Bewährungskontext der Tätigkeit. Erkennbar wird ein generationsspezifisches Individuationsbegehren, welches auf der Erfahrung wohlfahrtsstaatlicher Sicherung fußt und auf die Erosion eines Bildungs- und Aufstiegsversprechens trifft. In der Folge konstituiert eine spannungsreiche Verknüpfung von Selbstentfaltung und Statusunklarheit die Auseinandersetzung mit der sozialen Institution Biografie. Solo-Selbstständigkeit zeigt sich somit als ein hochgradig individualisiertes Erwerbsmuster, dessen Anschlussfähigkeit für das Projekt des „authentischen Selbst" erst vor dem Hintergrund generationsspezifischer Erfahrungen gewährter und entzogener Wohlfahrtsstaatlichkeit plausibel wird. „Alltagsgeschichte" als Exploration kleiner Lebenswelten Zusammenfassung Elizabeth T. Spira hat mit ihrem ganz eigenen Blick interessante Betrachtungsweisen zur österreichischen Gesellschaft und Alltagskultur geliefert. Anlässlich ihres Todes wird deshalb an ihre Leistungen als Sozialreporterin erinnert, auf soziologisch relevante Aspekte verwiesen und ihre Arbeit kritisch gewürdigt. Darüber hinaus werden zu diesem Anlass die Verbindungen und Abgrenzungen zwischen Sozialreportage und (Teilen der) Soziologie thematisiert. Anhand der Liebesg'schichten und Heiratssachen, vor allem aber der Alltagsgeschichten wird geprüft, inwiefern für die Soziologie und die Frage nach dem Zugang zur sozialen Wirklichkeit von den Arbeiten Spiras Impulse und Denkanstöße ausgehen können. Digitale Gesundheit: Was ändert sich für den Gesundheitsbegriff? Zusammenfassung Dieser Beitrag untersucht, wie sich mit der Entwicklung digitaler Gesundheitstechnologien das Verständnis von Krankheit und Gesundheit ändert. Digitale Technologien sind in einem bedeutsamen Sinn transgressiv. Sie gehen über die kurative und präventive Medizin hinaus und überschreiten die Grenzen zu einer wunscherfüllenden Medizin, die nach Verbesserung und Optimierung des menschlichen Körpers und seiner Leistungsfähigkeit sucht. Vor allem ist digitale Medizin eine Vision. Nicht, was es bereits gibt, sondern was möglich sein könnte, wird mit diesem Begriff in Verbindung gebracht. Digitale Medizin gibt ein Versprechen ab: Wenn es gelingt, medizinisches Wissen und gesundheitsbezogene Daten umfassend zu integrieren, wird es möglich, Krankheiten besser zu heilen, ja sogar ihr Auftreten zu verhindern. In Form eines medizinischen Avatars gießt sich diese Vision in eine konkrete technologische Gestalt. Ein solcher digitaler Zwilling stellt ein Abbild aller physiologischen und psychischen Vorgänge bereit, auf dessen Basis gesundheitsbezogene Prozessabläufe simuliert und therapeutische Maßnahmen evaluiert werden können. Aufgabe sozialwissenschaftlicher Reflexion ist es nun, im Sinne eines Vision Assessments die Implikationen neuer Technologien zu diskutieren, bevor sie Realität geworden sind. Besonders bedeutsam sind im diskutierten Zusammenhang die technologisch vermittelten Möglichkeiten eines lückenlosen Monitorings und einer umfassenden Simulation. Durch digitale Gesundheitstechnologien ändert sich nicht nur der Interventionsmodus medizinischen Handelns, sondern auch das, was wir autonomes Subjekt nennen. Gesundheit wird zu einer quantifizierbaren Zielvorgabe und zu einer Optimierungspraxis. Letztlich befördert dies die Ökonomisierung des Sozialen und verändert in tiefgreifender Weise, wie wir uns verhalten, um unsere Gesundheit zu erhalten, Krankheiten heilen oder präventiv verhindern. Im Feld der Verschwörungstheorien – Interaktionsregeln und kollektive Identitäten einer verschwörungstheoretischen Bewegung Zusammenfassung Trotz der steigenden politischen Bedeutung von Verschwörungstheorien gibt es bislang keine qualitativen soziologischen Auseinandersetzungen mit diesem Phänomen. Der vorliegende Beitrag versucht, diese Forschungslücke anhand von qualitativen Interviews mit Mitgliedern einer verschwörungstheoretischen Bewegung zu schließen. Dabei steht die Frage im Zentrum, wie Teilnehmerinnen dieser Bewegung mit internen inhaltlichen Differenzen umgehen und aller Heterogenität zum Trotz eine kollektive Identität ausbilden. Dabei zeigt sich, dass inhaltliche Differenzen ausgeklammert oder ignoriert werden. Während Verschwörungstheoretikerinnen von der Öffentlichkeit zumeist wörtlich, aber nicht ernst genommen werden, verhält es sich im Feld der Verschwörungstheorien umgekehrt. Verschwörungstheorien werden ernst, aber nicht wörtlich genommen. Die kollektive Identität der untersuchten Bewegung ergibt sich nicht aus einem geteilten Glauben an bestimmte Theorien, sondern aus einer kollektiven Opposition zur hegemonialen Wissensproduktion sowie dem gemeinsamen Zelebrieren herrschaftskritischer Lebensstile. Proving the world more imaginary? Abstract Sustainability research has set itself the double-challenge of uncovering the complexity of a globally, locally and historically unsustainable development path, and of contributing to a search process for more sustainable development paths for humanity. A small number of researchers involved in this area have suggested "that maybe the challenge of sustainability isn't to prove the world more real […] but to prove the world more imaginary" (Robinson as quoted in Taylor 2012, n. p.). Taking up this invocation of the imaginary, the article investigates some imaginaries and imagination of sustainability at play in sustainability research. Four relatively distinct approaches to sustainability research are identified, characterized and differentiated: "triple bottom-line", "sustainability transformation", "holistic healing/biophilia", and "culture of qualitative complexity". They each develop a specific focus, are nourished by partly different imaginaries and develop their imaginations in distinct directions. In this article, imagination is understood as an individual and social, perceptive and creative process by which we shape realities in our encounters with the world; whereas the imaginary is understood as a deep symbolic matrix that enables our access to the world. Imaginaries are not just made up and imposed on the world by the humans, but the result of an imaginative encounter with the human and other-than-human world. Focused attention on imagination and imaginaries not only allows to observe the area of sustainability research through a differentiating perspective that helps understand certain contrasting and/or shared features across different approaches to sustainability research. This focused attention also bears a potentially instrumental value for inter- and transdisciplinary sustainability research itself, because it encourages sustainability researchers to further reflect on the importance, modalities and different framings of creative and reflective approaches to futures-oriented research agendas. The creative exercise of the imagination is not only at the core of "anticipatory competences" (Wiek et al. 2011, p. 7) for sustainability, but also at the core of percipience to nature-culture's dynamic complexity. In this respect, sustainability research needs to develop its self-reflexivity beyond discourse-rational approaches to narratives, with a deeper understanding of both embodied cognition and of culture. Reflection on, and radically imaginative work with both dominant and alternative imaginaries that sustainability researchers operate from, such as the four imaginaries discussed in this article, are a precondition to any movement beyond institutional path-dependency to a globally unsustainable development. Social imaginaries and the limits of differential meaning Abstract Elaborating on theories of the social imaginary, this contribution addresses the shortcomings of a differential conception of meaning, which is widespread in the social and cultural sciences. After a brief literature review, a preliminary concept of the social imaginary and its sociological relevance will be outlined drawing on the works of Taylor and others. The theoretical argument of this article, the fundamental difference and complementarity between the differential logic of the symbolic and the fuzzy logic of the imaginary, will be developed in a discussion of structuralism and one of its most fervent critics: Castoriadis. The latter developed his account of the social imaginary as a critique of Marxist reductionism, of the structuralist analysis of language and totemism, and of "ensemblistic-identitarian logic" in general. The implications of Castoriadis' "imaginary significations"—a "magma" of meaning not exhausted by the differential order of signs—will be demonstrated discussing two contemporary sociological theories informed by structuralism as well as poststructuralism: Luhmann's system theory and the cultural sociology of Alexander and Smith. The social imaginary, as a reservoir of meaning and condition for the emergence of new meanings, not only illuminates the blind spots in these theories, but also has the potential to transform our thinking about culture and society. Das Imaginäre der Praxis Zusammenfassung Gegenwärtige Praxistheorie tendiert, so der Ausgangspunkt des Artikels, zu einem Ordnungsbias. Sie sieht letztlich keinen systematischen Ort für das Denken und Aufspüren von Momenten vor, die sich dem Gelingen von Praktiken entziehen oder widersetzen. Entsprechend thematisiert sie Probleme nahezu ausschließlich als interne Vollzugsprobleme, nicht aber als in Praktiken bearbeitete Bezugsprobleme. Mit Castoriadis' Begriff des Imaginären als einer schöpferischen Kraft, die sich in einem Andersmachen entfalten kann, bringen wir demgegenüber ein Beobachtungskonzept in die Praxistheorien ein, das es der praxeologischen Analyse erlaubt, aufzuspüren und zur Sprache zu bringen, was eine gegebene Ordnung auf etwas hin überschreitet, das in ihr angelegt, aber (noch) nicht entfaltet ist. Exemplarisch wird der mit Castoriadis zu erringende wissenschaftliche Landgewinn an Gegenwartsdiagnosen angedeutet, einem historischen Typ der symbolischen Repräsentation von Gesellschaft, der Bezugsprobleme erzeugt, vor deren Sinnhorizont sich die symbolische Ordnung in der Moderne entwirft. Am empirischen Beispiel der gegenwartsdiagnostisch durch Umweltdiskurse informierten Praktiken eines Öko-Dorfes wird aufgewiesen, dass einem solchen Entwurf über Planungsrationalität hinaus stets auch ein Potential der Kritik innewohnt, das Alternativen zum Bestehenden eröffnet. Auf dieser theoretischen und empirischen Folie mündet der Artikel in eine (Selbst‑)Kritik gegenwärtiger Praxistheorie und einen Ausblick auf Praxiskonzeptionen, die dem Ordnungsbias zu entgehen versprechen. Theorien des gesellschaftlichen Imaginären Zusammenfassung Im Anschluss an Cornelius Castoriadis' Konzept der Gesellschaft als imaginäre Institution lotet der Beitrag das theoretische und gesellschaftsanalytische Potential der Kategorie des gesellschaftlichen Imaginären aus. Die These ist: „Gesellschaft" erscheint in dieser französischen Theorietradition als dreifach kontrafaktische Imagination: als vorgestellte Identität in der Zeit; als vorgestellte Einheit der Mitglieder; als Fundierung des Kollektivs im imaginären Außen oder dem gesellschaftlichen Grund. Eine solche Theorie interessiert sich für die Konstitution von Gesellschaften, indem sie diese nicht allein auf die Identitätsbildung via Differenz bezieht, sondern ebenso auf die Erfindung einer Identität in der Zeit und vor allem das fundierende Außen. Der Beitrag zielt auf eine umfassende Theorie der Gesellschaft als imaginärer Institution. Dazu bezieht er neben Castoriadis weitere Konzepte ein, klassische Traditionen (Émile Durkheim, Henri Bergson) und an Castoriadis anschließende, historisch-vergleichende Gesellschaftsanalysen (Marcel Gauchet, Claude Lefort). Schließlich wird das gegenwartsanalytische Potential einer solchen Theorie des gesellschaftlichen Imaginären angedeutet.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Infectious Disease Management and Control with Povidone Iodine In the original publication, Figure 1 was incorrectly published. The correct figure is given here. Specific Varicella-Related Complications and Their Decrease in Hospitalized Children after the Introduction of General Varicella Vaccination: Results from a Multicenter Pediatric Hospital Surveillance Study in Bavaria (Germany) AbstractBackground Universal varicella vaccination (UVV) for children introduced in Germany in 2004 resulted in a significant overall decline of varicella-related hospitalizations (VRHs). We investigated the incidence of specific types of varicella-related complications (VRCs) in hospitalized children and the impact of UVV on VRCs during the first 7 years of UVV.Methods Children < 17 years of age hospitalized with an ICD-10-based (International Classification of Diseases, 10th Revision) discharge diagnosis of varicella were identified as VRH in pediatric hospitals in Bavaria by annual standardized data queries of the hospital databases (2005–2011). For each VRH, the hospitals reported basic demographic data, duration of hospital stay, all diagnostic and procedural codes, and outcome. VRCs were reported overall, per year, and by immune status. Complication rates were calculated as mean number per complication category per hospital and per year; VRC trends over time were assessed by linear regression.Results Between 78% (2005) and 61% (2011) of Bavarian hospitals participated and reported a total of 1263 VRHs. Specific VRCs were reported in 954 (76%) children. Complication rates per hospital and year decreased from 6.7 [95% confidence interval (CI): 5.1–8.3] in 2005 to 1.5 (95% CI: 0.8–2.3) in 2011, with the strongest reduction of 90% in children < 5 years of age from 5.3 (95% CI: 4.0–6.6) in 2005 to 0.5 (95% CI: 0.1–0.9) in 2011. Significant decreases were observed for children with upper respiratory tract (URT, by 97%), lower respiratory tract (LRT, by 90%), skin (by 81%), gastrointestinal (by 78%), and neurologic (by 65%) VRCs. Forty-eight children with VRCs were immunocompromised; their annual rate decreased by 87%.Discussion Corresponding to increasing varicella vaccination coverage in the population, the incidence of VRC decreased by 77% from 2005 to 2011, with the most substantial decrease in the target group for UVV.Conclusion Within 7 years, UVV in Germany led to a decrease of about 77% of all types of VRCs, with the highest reductions observed for VRCs of the respiratory tract. A Community-Based Survey to Assess Knowledge, Attitudes, Beliefs and Practices Regarding Herpes Zoster in an Urban Setting AbstractIntroduction In the USA, nearly one in three people will experience herpes zoster (HZ) in their lifetime. Underserved communities may be at even higher risk due to several factors, including access to healthcare, education, and co-morbid conditions. The purpose of this study was to investigate current knowledge, attitudes, beliefs and practices (KABP) relative to HZ and HZ vaccines in a large urban city.Methods A cross-sectional KABP survey was conducted via in-person interview among 381 participants aged ≥ 50 years in Detroit, MI, USA, from June to August 2018. Survey results were stratified into two groups [< 60 and ≥ 60 years of age (YO)] for comparison.Results Of the 381 participants, 373 reported their age (110 < 60 YO and 263 ≥ 60 YO). Overall, the majority of participants reported having heard of HZ and HZ vaccines. In addition, receiving a recommendation from a healthcare provider (37.5%) followed by gaining a better understanding of HZ vaccine (36.7%) and of HZ (29.9%) were leading factors that influenced participants' willingness to receive the vaccine. Of note, 65.5% of participants < 60 YO reported the belief that HZ is preventable versus only 53.2% in those ≥ 60 YO (p = 0.001).Conclusion Our findings underscore the need to educate patients in underserved communities about HZ as well as new HZ vaccine recommendations to improve vaccination rates and reduce the incidence of HZ and its associated sequelae. Immunological and Clinical Benefits of Maternal Immunization Against Pertussis: A Systematic Review Abstract Infants are vulnerable to pertussis infection particularly before initiation of pertussis vaccination. Maternal pertussis vaccination during pregnancy has been introduced in a number of countries in order to confer on young infants indirect protection from the disease through transplacental transfer of maternal antibodies. We reviewed the evidence on the immunogenicity and efficacy of maternal pertussis vaccination during pregnancy. A systematic search of PubMed/MEDLINE, EMBASE, Scopus, Cochrane Database of Systematic Reviews, ProQuest, and Science Direct was undertaken to identify studies published between January 1995 and December 2018. This review was not specific to any particular pertussis vaccine but included applicable data on available pertussis vaccines administered to pregnant women. The search identified 40 publications for inclusion in this review. Vaccination during pregnancy elicited robust maternal immune responses against all vaccine antigens and resulted in high placental transfer of pertussis antibodies to the infant that persisted well beyond delivery. Vaccination during the second or early third trimesters was considered ideal for antibody quantity and functionality. Although blunting of immune responses to some antigens in the primary immunization series was documented in neonates born to women vaccinated during pregnancy, there was no apparent adverse effect on vaccine efficacy. Multiple studies conducted in diverse settings have confirmed the effectiveness of maternal pertussis vaccination during pregnancy in preventing pertussis in infants prior to receipt of their first primary vaccine dose and beyond. These findings collectively underscore the value of maternal pertussis vaccination during pregnancy in protecting vulnerable infants too young to be vaccinated. Funding Sanofi Pasteur. Plain Language Summary Plain language summary available for this article. Safety, Resistance, and Efficacy Results from a Phase IIIb Study of Conventional- and Double-Dose Oseltamivir Regimens for Treatment of Influenza in Immunocompromised Patients AbstractIntroduction Immunocompromised patients infected with influenza exhibit prolonged viral shedding and higher risk of resistance. Optimized treatment strategies are needed to reduce the risk of antiviral resistance. This phase IIIb, randomized, double-blind study (NCT00545532) evaluated conventional-dose or double-dose oseltamivir for the treatment of influenza in immunocompromised patients.Methods Patients with primary or secondary immunodeficiency and influenza infection were randomized 1:1 to receive conventional-dose oseltamivir (75 mg adolescents/adults [≥ 13 years]; 30–75 mg by body weight in children [1–12 years]) or double-dose oseltamivir (150 or 60–150 mg, respectively), twice daily for an extended period of 10 days. Nasal/throat swabs were taken for virology assessments at all study visits. Co-primary endpoints were safety/tolerability and viral resistance. Secondary endpoints included time to symptom alleviation (TTSA) and time to cessation of viral shedding (TTCVS).Results Of 228 patients enrolled between February 2008 and May 2017, 215 (199 adults) were evaluable for safety, 167 (151 adults) for efficacy, and 152 (138 adults) for resistance. Fewer patients experienced an adverse event (AE) in the conventional-dose group (50.5%) versus the double-dose group (59.1%). The most frequently reported AEs were nausea, diarrhea, vomiting, and headache. Fifteen patients had post-baseline resistance, more commonly in the conventional-dose group (n = 12) than in the double-dose group (n = 3). In adults, median TTSA was similar between arms, while median TTCVS was longer with conventional dosing.Conclusions Oseltamivir was well tolerated, with a trend toward better safety/tolerability for conventional dosing versus double dosing. Resistance rates were higher with conventional dosing in this immunocompromised patient population.Trial Registration ClinicalTrials.gov identifier: NCT00545532.Funding F. Hoffmann-La Roche Ltd. Use of Antifungals and Outcomes Among Inpatients at Risk of Invasive Aspergillosis or Mucormycosis in the USA: A Retrospective Cohort Study AbstractIntroduction Prophylaxis and treatment of invasive aspergillosis (IA) and mucormycosis (IM) within a real-world US inpatient setting is undocumented since the introduction of isavuconazole. This retrospective medical record review aimed to describe characteristics, triazole use, and outcomes among inpatients across the USA who initiated antifungal monotherapy (AFMT) as prophylaxis or treatment of IA/IM.Methods A convenience sample of US physicians abstracted data from randomly selected records of hospitalized patients aged ≥ 18 years initiating AFMT (amphotericin B, isavuconazole, voriconazole, or posaconazole) as prophylaxis or treatment of IA/IM between 2013 and 2017. Retrieved data included background characteristics, dosage and duration of AFMT, healthcare resource use, and survival. Characteristics and outcomes were compared (prophylaxis vs treatment) using Fisher's exact and one-way analysis of variance tests where applicable. Exploratory Kaplan–Meier analyses described overall and inpatient survival.Results Physicians (n = 23) retrieved 124 patient records (43 prophylaxis; 81 treatment). Median duration of first-line AFMT was 14 days (range 1–603 days) and 19 days (range 3–351 days) in the prophylaxis and treatment groups, respectively. One patient received second-line therapy. Median duration of hospitalization was 29 days (range 4–259 days) and 31 days (range 6–980 days) in the prophylaxis and treatment groups, respectively. Admission to intensive care occurred in 14% and 52% of patients in the prophylaxis and treatment groups, respectively. At the time of data retrieval, overall and inpatient survival rates in the prophylaxis group were 88% and 87%, respectively, and in the treatment group were 66% and 76%, respectively.Conclusions This study documented real-world prophylactic and therapeutic AFMT use for IA/IM and associated outcomes among hospitalized patients in the USA since approval of isavuconazole. IA/IM were associated with lengthy hospital stays commonly requiring intensive care. Prophylactic and therapeutic AFMT dosages and duration generally followed recommendations and switching between agents was rare.Funding Astellas Pharma Global Development, Inc., Northbrook, IL, USA. Incidence and Prevention of Invasive Meningococcal Disease in Global Mass Gathering Events AbstractIntroduction Mass gathering events involve close contact among large numbers of people in a specific location at the same time, an environment conducive to transmission of respiratory tract illnesses including invasive meningococcal disease (IMD). This report describes IMD incidence at mass gatherings over the past 10 years and discusses strategies to prevent IMD at such events.Methods A PubMed search was conducted in December 2018 using a search string intended to identify articles describing IMD at mass gatherings, including religious pilgrimages, sports events, jamborees, and refugee camps. The search was limited to articles in English published from 2008 to 2018. Articles were included if they described IMD incidence at a mass gathering event.Results A total of 127 articles were retrieved, of which 7 reported on IMD incidence at mass gatherings in the past 10 years. Specifically, in Saudi Arabia between 2002 and 2011, IMD occurred in 16 Hajj pilgrims and 1 Umrah pilgrim; serotypes involved were not reported. At a youth sports festival in Spain in 2008, 1 case of serogroup B IMD was reported among 1500 attendees. At the 2015 World Scout Jamboree in Japan, an outbreak of serogroup W IMD was identified in five scouts and one parent. At a refugee camp in Turkey, one case of serogroup B IMD was reported in a Syrian girl; four cases of serogroup X IMD occurred in an Italian refugee camp among refugees from Africa and Bangladesh. In 2017, a funeral in Liberia resulted in 13 identified cases of serogroup C IMD. Requiring meningococcal vaccination for mass gathering attendees and vaccinating refugees might have prevented these IMD cases.Conclusions Mass gathering events increase IMD risk among attendees and their close contacts. Vaccines preventing IMD caused by serogroups ACWY and B are available and should be recommended for mass gathering attendees.Funding Pfizer. Infectious Disease Management and Control with Povidone Iodine Abstract With reports of vancomycin-resistant enterococci recently emerging in hospital settings, renewed focus is turning to the importance of multifaceted infection prevention efforts. Careful compliance with established hygiene practices by healthcare workers together with effective antiseptic options is essential for the protection of patients from infectious agents. For over 60 years, povidone iodine (PVP-I) formulations have been shown to limit the impact and spread of infectious diseases with potent antiviral, antibacterial and antifungal effects. In addition to a lack of reported resistance, the benefits of PVP-I include an excellent safety profile and a broad spectrum of effect due to its multimodal action. Studies have shown that hand washing with PVP-I-based antiseptics is effective for the decontamination of skin, while PVP-I mouthwashes and gargles significantly reduce viral load in the oral cavity and the oropharynx. The importance of PVP-I has been emphasised by its inclusion in the World Health Organization's list of essential medicines, and high potency for virucidal activity has been observed against viruses of significant global concern, including hepatitis A and influenza, as well as the Middle-East Respiratory Syndrome and Sudden Acute Respiratory Syndrome coronaviruses. Together with its diverse applications in antimicrobial control, broad accessibility across the globe, and outstanding safety and tolerability profile, PVP-I offers an affordable, potent, and widely available antiseptic option. Funding Mundipharma Singapore Holding Pte Limited. Safety of Maternal Immunization Against Pertussis: A Systematic Review Abstract The WHO recommends vaccination of all children against pertussis. However, newborn infants remain vulnerable to infection. Pertussis vaccination during pregnancy has been introduced in several countries to protect newborns via transplacental transfer of maternal pertussis antibodies to the infant. We reviewed the impact of maternal pertussis vaccination on the health of pregnant women, the developing fetus, and health of the newborn. We searched PubMed/MEDLINE, EMBASE, Scopus (Elsevier), Cochrane Database of Systematic Reviews, ProQuest, and Science Direct to identify studies that assessed the safety of maternal pertussis vaccination. Twenty-seven English language publications published between January 1995 and December 2018 were included in this review. Pregnant women receiving pertussis vaccines did not have increased rates of systemic or local reactions. There were no safety concerns with repeat vaccination with other tetanus-containing vaccines or their concomitant administration with influenza vaccines. Maternal pertussis vaccination did not adversely affect pregnancy, birth or neonatal outcomes. This review confirms the safety of maternal pertussis vaccination during pregnancy.Funding Sanofi Pasteur.Plain Language Summary Plain language summary available for this article. The Intestinal Microbiota as a Reservoir and a Therapeutic Target to Fight Multi-Drug-Resistant Bacteria: A Narrative Review of the Literature Abstract The appearance and dissemination of antibiotic-resistant bacteria, particularly in specific closed environments such as intensive care units of acute care hospitals, have become a major health concern. The intestinal microbiota has various functions including host protection from overgrowth or colonization by unwanted bacteria. The exposure to antibiotics significantly reduces the bacterial density of intestinal microbiota leaving an ecologic void that can be occupied by potentially pathogenic and/or resistant bacteria frequently present in hospital settings. Consequently, the intestinal microbiota of inpatients acts as a major reservoir and plays a critical role in perpetuating the spread of resistant bacteria. There are novel innovative methods to protect the host microbiota during antibiotic treatment, but they do not offer a solution for already established colonization by resistant microorganisms. Fecal microbiota transfer (FMT) is a promising intervention to achieve this goal; however, controlled trials report lower success rates than initial retrospective studies, especially in case of gram negatives. The aim of the present article is to highlight the importance of the intestinal microbiota in the global spread of multi-drug-resistant (MDR) microorganisms and to review the recent advances to protect the human microbiota from the action of antibiotics as well as a critical discussion about the evidence of decolonization of MDR microorganisms by FMT.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Effects of a Self-Management with Peer Training Intervention on Academic Engagement for High School Students with Autism Spectrum Disorder Abstract Self-management interventions have been shown to improve behavioral, social, and academic outcomes across age-groups and settings; yet, a dearth of research exists on the impact of self-management interventions on academic engagement of high school students with autism spectrum disorder (ASD). The present study uses an ABAB withdrawal design to examine the effects of a self-management with peer trainer (SM + PT) intervention on the academic engagement of two high school students with ASD. The peer trainer in this study also had ASD. Additionally, the study examines the extent to which the peer trainer with ASD implemented a peer training session with fidelity and the social validity of the SM + PT intervention. Based on the What Works Clearinghouse Procedures and Standards Handbook guidelines (Institute of Education Sciences 2017), this study found moderate evidence for a causal relationship of the SM + PT intervention and academic engagement for both students. Data suggest that the peer trainer implemented the peer training component with fidelity. Social validity results suggest that the intervention was feasible, acceptable, and effective. Limitations include the presence of naturally occurring variations in the teacher-assigned tasks, school-imposed time constraints, and data outliers in both students' second baseline phases. Future research is needed to investigate the extent to which SM + PT interventions can be effectively implemented and generalized to more inclusive high school settings. Teaching Leisure Activities with Social Initiations Through Video Prompting Abstract Children with autism typically have a limited repertoire of activities they engage in during their free time and are often observed to engage in inappropriate or non-functional play. Previous research has suggested that deficits in leisure skills are not only a factor of the diagnosis, but also influenced by structural constraints such as lack of resources, support, and opportunity. This study used a multiple probe across participants design to assess the effects of video prompting and error correction on the acquisition of a leisure activity and social initiation for three children with autism. Results indicate that video prompting may be effective in increasing appropriate engagement in a leisure activity. However, findings are mixed concerning the use of video prompting to teach a social initiation. This study expands on previous research by systematically selecting a leisure activity to teach and by including a social component. Incorporating the Portable Operant Research and Teaching Laboratory into Undergraduate Introduction to Behavior Analysis Courses Abstract The use of operant chambers for research and teaching in behavior analysis is in decline due to the expense, maintenance, and ethical considerations of such complex mechanical apparati (Venneman and Knowles in Teach Psychol 32(1):66–68, 2005. https://doi.org/10.1207/s15328023top3201_13). Other technologies for testing and demonstrating behavioral principles have emerged in the pursuit of creating free operant paradigms that are accessible and effective for students and economical for institutions. One example is virtual programs that emulate the behavior of organisms such as CyberRat and Sniffy (Graham et al. in Behav Res Methods Instrum Comput 26(2):134–141, 1994. https://doi.org/10.3758/bf03204606; Ray in CyberRat (version 1.0), Brown & Benchmark, Madison, 1996; Behav Philos 39:203–301, 2011). Recently, a new instrument has been developed—the Portable Operant Research and Teaching Lab (PORTL; Rosales-Ruiz and Hunter in Operants 4:34–36, 2016). PORTL is a tabletop apparatus comprised of various objects and tools that enable students to experience and manage free operant situations. In addition to its instructional benefits, PORTL provides a setting for basic research to be completed quickly and ethically with human participants. The purpose of this paper is to outline how to incorporate PORTL into undergraduate behavior analysis courses. Several examples of how PORTL has been incorporated into such courses, including sample exercises, are provided as a model for other course instructors. Interdependent Group Contingencies Reduce Disruption in Alternative High School Classrooms Abstract Group contingencies have been indicated to be effective in reducing disruptive behavior and increasing academic engagement in school settings. Previous research has demonstrated their efficacy with a wide range of student ages, but there have been few studies with older students who engage in severe disruptive behavior. In the current study, we implemented an interdependent group contingency in three high school classrooms of students aged 14–19 years with histories of delinquency, emotional and behavioral disorder diagnoses, or both. Results indicated that interdependent group contingencies can be effective in reducing the disruptive classroom behavior of these students. Implications for future research and special considerations for this population are discussed. The Effects of the Concrete-Representational-Abstract Sequence for Students at Risk for Mathematics Failure Abstract Students who have difficulty with mathematics may have trouble understanding underlying concepts of numbers and operations. The concrete-representational-abstract (CRA) instructional sequence of instruction provides a way for teachers to help students gain meaning from numbers and the mathematical concepts those numbers represent. This study addresses evidence-based practices and applies CRA methods to instruction address concepts such as rounding, regrouping, and equivalent fractions. The purpose of this study was to investigate the effects of CRA instruction on the performance of elementary students across varied areas of need related to poor conceptual understanding and proficiency in completing tasks related to numbers and operations. The researchers implemented a multiple baseline across behaviors design for two students who were at risk for mathematics failure. A functional relation was found for CRA intervention and rounding, regrouping, and fraction concepts for the two students. Results and implications are discussed. Using Brief Experimental Analysis to Identify the Right Math Intervention at the Right Time Abstract Brief experimental analysis (BEA) is a methodology of rapidly implementing interventions and observing the effect each has on student performance. Extensive research exists demonstrating the utility of BEA in identifying effective reading interventions for students, but comparatively little research exists regarding BEA and mathematics. The current study utilized BEA procedures to identify an intervention targeting skill- or performance-based deficits that would be effective for remediating 4 middle school students' two-digit by two-digit multiplication skills. Each student had a clearly differentiated intervention identified by BEA as being most effective. Findings from the current study provide evidence for the utility of BEA in matching deficits with mathematics interventions and illustrate their sensitivity to changes in student performance. Exploring Procedural Manipulations to Enhance Student Performance on SAFMEDS in Undergraduate Introduction to Behavior Analysis Courses Abstract Research into the fluency-building tactic named Say All Fast Minute Every Day Shuffled (SAFMEDS) has implications for instruction at all academic levels. Several researchers have studied the effects of SAFMEDS in undergraduate courses; however, not all of the salient variables, or the relationships among variables, have been fully analyzed. The numerous procedural variations may pose specific challenges for college instructors who wish to implement SAFMEDS in their course design or for students who are attempting to use SAFMEDS on their own. We collected behavioral data across four semesters of undergraduate introductory behavior analysis courses. The effects of two procedural manipulations were evaluated in relation to undergraduate students' performance frequencies on weekly checkouts with two or four decks of see term/say definition SAFMEDS. The authors describe how SAFMEDS were implemented and modified over the course of four semesters of instruction. SAFMEDS' procedures were modified each semester based on student outcomes in the prior semester in an effort to improve our student outcomes and to assist other course instructors who might wish to utilize SAFMEDS in their university courses. An overview of the decision-making process and student outcomes allows for the authors to make recommendations for course instructors who employ SAFMEDS in their courses and suggestions for future research to improve our understanding of how SAFMEDS affect student performance. Effect of Task Sequence and Preference on On-Task Behavior Abstract This study compared effects of student choice of task sequence to two variations in teacher-manipulated task sequences on on-task behavior of elementary-aged students with disabilities. Researchers modified Call et al.'s (J Appl Behav Anal 42: 723–728, 2009) demand assessment to determine high-, moderate-, and low-probability tasks. Next, researchers applied the results from the demand assessment to inform teacher-manipulated variations in task sequences: a high- to low-probability task sequence and low- to high-probability task sequence. These sequences were then embedded in a visual activity schedule (VAS). Results of task sequence manipulation embedded in a VAS indicated slightly higher median percentages of on-task behavior for the high- to low-probability task sequence. Future directions for research based on these preliminary data are discussed. A Systematic and Quality Review of Parent-Implemented Language and Communication Interventions Conducted via Telepractice Abstract The purpose of this study was to systematically review the literature researching telepractice and parent-implemented language and communication interventions. A total of 12 studies met inclusion criteria and comprise the final study sample. A majority of the included articles were single-case research studies, and two were randomized controlled trials. We analyzed participant characteristics, intervention types, outcomes, and research quality in all 12 studies. All telepractice-based parent-implemented interventions reported improvements in parent and/or child outcomes. We evaluated the rigor of the studies against single-case research and group design quality indicators as well as What Works Clearinghouse standards. Of the 10 single-case research studies, one met single-case research design standards and six met standards with reservations, and of the two group design studies, only one met all quality indicators and standards. Results are discussed and future directions are provided. Effects of Response Cards on Fourth-Grade Students' Participation and Disruptive Behavior During Language Arts Lessons in an Inclusive Elementary Classroom Abstract Many teachers state that disruptive behavior in their classroom is one of their main challenges, and it often results in a loss of instructional time. Teachers also have difficulty in providing opportunities for their students to be actively engaged in their own learning. This study used an ABAB reversal design to investigate the effects of preprinted response cards on students' participation and disruptive behavior in a fourth-grade inclusive elementary classroom during language arts instruction. The findings of this study showed that the use of preprinted response cards resulted in increased participation for all five target students. Limitations of the study, areas for future research to investigate, and implications for practice are discussed.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Neurosurgical Interventions for Neurotrauma in the Obstetric Population: A Systematic Review Trauma requiring neurosurgical intervention in the obstetric population is rare. Provision of care must include consideration for both maternal and fetal well-being, and conflicts may arise. Management strategies to reduce elevated maternal intracranial pressure (ICP) and provide adequate surgical exposure, for example, may compromise uteroplacental perfusion. There is scarce literature to guide anesthetic care and few resources summarizing management of these uncommon cases. We conducted a systematic literature search for English publications of neurosurgical interventions on obstetric patients following trauma. We searched MEDLINE, EMBASE, and Google Scholar from inception to May 1, 2019. We identified 18 cases from 13 publications including 9 case reports and 4 case series. Median Glasgow coma scale on presentation was 6, good maternal outcome occurred in 39% of cases, and good fetal outcome occurred in 67% of cases. Qualitative review of the articles suggests an initially low Glasgow coma scale on admission commonly resulted in worse maternal and fetal outcomes. Delivery occurred postneurosurgical intervention in the majority of viable fetuses. Few details were available regarding anesthetic management, and ICP management strategies varied widely. Our review identified only a small number of case reports and case series. Maternal outcomes were generally poor, although the majority of fetal outcomes were good. Although there seems to be a relationship between outcomes and severity of maternal injury on presentation, it is difficult to draw conclusions or make recommendations because of limited data on perioperative anesthetic and ICP management strategies. Regardless of gestational age, maternal supremacy must be upheld. Our results are limited by the quality of the available research and potential selection bias. Previous presentations of this work: oral and poster presentation at the American Society of Anesthesiologists (ASA) Annual Meeting. Additional poster presentation at the Society for Neuroscience in Anesthesiology and Critical Care (SNACC) Annual Meeting (October 2018; San Francisco, CA). The authors have no funding or conflicts of interest to disclose. Address correspondence to: Christie M. Addison, MD. E-mail: Christie.fitch@alumni.ubc.ca. Received May 10, 2019 Accepted October 15, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved JNA Is Looking Forward to 2020 and Beyond No abstract available Perceived Benefits and Barriers to a Career in Neuroanesthesiology: A Pilot Survey of Anesthesiology Clinicians Background: Despite advances in perioperative neuroscience, there is low interest among anesthesiology trainees to pursue subspecialty training in neuroanesthesiology. We conducted a pilot survey to assess attitudes about neuroanesthesiology fellowship training. Materials and Methods: A confidential survey was distributed to an international cohort of anesthesiology attendings and trainees between January 15, 2017 and February 26, 2017. Results: A total of 463 responses were received. Overall, 309 (67%), 30 (6%), 116 (25%), and 8 (2%) of respondents identified themselves as attendings, fellows, residents, and "other," respectively. In total, 390 (84%) of respondents were from the United States. Individuals typically pursue anesthesiology fellowship training because of interest in the subspecialty, acquisition of a special skill set, and the role of fellowship training in career planning and advancement. Overall, 64% of attendings, 56% of fellows, and 55% of residents favored accreditation of neuroanesthesiology fellowships, although opinion was divided regarding the role of accreditation in increasing interest in the specialty. Respondents believe that increased opportunities for research and greater exposure to neurocritical care and neurological monitoring methods would increase interest in neuroanesthesiology fellowship training. Perceived barriers to neuroanesthesiology fellowship training were perceptions that residency provides adequate training in neuroanesthesiology, that a unique skill set is not acquired, and that there are limited job opportunities available to those with neuroanesthesiology fellowship training. Conclusions: In this pilot survey, we identified several factors that trainees consider when deciding to undertake subspecialty training and barriers that might limit interest in pursuing neuroanesthesiology subspecialty training. Our findings may be used to guide curricular development and identify factors that might increase interest among trainees in pursuing neuroanesthesiology fellowship training. Presented in abstract form at the 45th Annual Meeting of the Society for Neuroscience in Anesthesiology and Critical Care in Boston, MA on October 20, 2017. The authors have no funding or conflicts of interest to disclose. Address correspondence to: Shobana Rajan, MD. E-mail: shobanarajan5@gmail.com. Received June 26, 2019 Accepted September 16, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved Erector Spine Plane Block at the T12 Level may not Provide Good Postoperative Pain Relief Following Lumbosacral Spine Surgery No abstract available Reporting Quality Analysis of Randomized Controlled Trials in Journal of Neurosurgical Anesthesiology: A Methodological Assessment Background: Randomized controlled trials (RCTs) are considered to provide high levels of evidence to optimize decision-making for patient care, although there can be a risk bias in their design, conduct, and analysis. Quality assessment of RCTs is necessary to assess whether they provide reliable results with little bias. Materials and Methods: We assessed the reporting quality of RCTs published in the Journal of Neurosurgical Anesthesiology (JNA) between January 1, 2000 and December 31, 2017 using the Jadad scale, van Tulder scale, and Cochrane Collaboration Risk of Bias Tool (CCRBT). Results: We identified 130 RCTs and 570 original articles. Among the 130 RCTs, 92 (70.8%) presented an appropriate blinding method, and 70 (53.8%) described an appropriate allocation method. For the entire period, the percentages of high-quality reporting articles were 71.5%, 73.1%, and 13.8% in the Jadad scale, van Tulder scale, and CCRBT assessments, respectively. There was an improvement in the van Tulder scale over time (coefficients [95% confidence interval {CI}]=0.08 [0.01-0.15]; P=0.02). Appropriate reporting of allocation in the Jadad scale (coefficients [95% CI]=1.68 [1.28-2.07]; P<0.001) and van Tulder scale (coefficients [95% CI]=2.34 [1.97-2.70]; P<0.001), and reporting of blinding in the Jadad (coefficients [95% CI]=1.09 [0.66-1.52]; P<0.001) and van Tulder scores (coefficients [95% CI]=1.85 [1.45- 2.25]; P<0.001), were associated with high-quality reporting. Conclusions: The ratio of high-quality reporting RCTs in JNA was consistently high compared with other journals. Thorough consideration of allocation concealment during the peer review process can further improve the reporting quality of RCTs in JNA. The authors have no funding or conflicts of interest to disclose. Address correspondence to: Kyu Nam Kim, MD, PhD. E-mail: vesicle100@naver.com. Received June 5, 2019 Accepted September 24, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved Assessment of Anesthesia Practice Patterns for Endovascular Therapy for Acute Ischemic Stroke: A Society for Neuroscience in Anesthesiology and Critical Care (SNACC) Member Survey Background: The choice of general anesthesia (GA) or conscious sedation (CS) may impact neurological outcomes of patients undergoing endovascular therapy (EVT) for acute ischemic stroke (AIS). The aim of this survey was to describe the practice patterns of members of the Society for Neuroscience in Anesthesiology and Critical Care (SNACC) for anesthetic management of AIS. Methods: Following institutional review board approval, a 16-question online survey assessing anesthetic management of patients with AIS undergoing EVT was circulated to members of SNACC. Results: A total of 76 SNACC members from 52 institutions and 11 countries completed the survey (12.5% response rate). Overall, 33% of institutions reported dedicated neuroanesthesia teams for EVT. Patients treated with GA ranged from 5% to 100% between centers. In total 51% and 49% of centers in the United States reported preferentially providing GA and CS, respectively, compared with 34% and 66%, respectively, in European centers. Reported anesthetic induction agents are propofol (64%), etomidate (4%) and either medication (33%). For maintenance of GA, volatile anesthetic is used more often (54%) than propofol (16%). There was wide variation in medications used for CS. Arterial catheter placement was reported by 75% and 43% of respondents for patients undergoing GA and CS, respectively. Systolic blood pressure >140 mm Hg was targeted by 35.7% of respondents, with others targeting mean arterial pressure within 10%, 20% or 30% of baseline values. Phenylephrine and norepinephrine were the most commonly used vasopressors. Conclusions: There is wide variation in anesthesia technique and hemodynamic management during EVT for AIS, and no consensus on the choice of, or preferred medications for, GA or CS, or target blood pressure and management of hypotension during the procedure. C.P. and D.S. are members of the Editorial Board of the Journal of Neurosurgical Anesthesiology. The remaining authors have no conflicts of interest to disclose. Address correspondence to: Deborah A. Rusy, MD, MBA. E-mail: darusy@wisc.edu. Received March 23, 2019 Accepted October 1, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved Anesthesia During Positive-pressure Myelogram: A New Role for Cerebral Oximetry Background: Positive-pressure myelogram (PPM) is an emerging radiologic study used to localize spinal dural defects. During PPM, cerebrospinal fluid pressure (CSFp) is increased by injecting saline with contrast into the cerebrospinal fluid. This has the potential to increase intracranial pressure and compromise cerebral perfusion. Methods: We performed a retrospective chart review and analysis of 11 patients. The aim was to describe the periprocedural anesthetic management of patients undergoing PPM. Results: All patients underwent PPM with general anesthesia and intra-arterial blood pressure and near-infrared spectroscopy monitoring of regional cerebral tissue oxygen saturation. Mean±SD maximum lumbar CSFp was 58±12 mm Hg. Upon intrathecal injection, mean systolic blood pressure increased from 115±21 to 142±32 mm Hg (P<0.001), diastolic blood pressure from 68±12 to 80±20 mm Hg (P≤0.001), and mean blood pressure from 87±10 to 98±14 mm Hg (P=0.02). Ten of 11 patients received blood pressure augmentation with phenylephrine to minimize the risk of reduced cerebral perfusion secondary to increased CSFp after intrathecal injection. The mean heart rate before and following injection was similar (68±15 vs. 70±15 bpm, respectively; P=0.16). There was a decrease in regional cerebral oxygen saturation after positioning from supine to prone position (79±10% to 74±9%, P=0.02) and a further decrease upon intrathecal injection (75±10% to 69±9%, P≤0.01). Conclusions: Systemic blood pressure increased following intrathecal injection during PPM, possibly due to a physiologic response to intracranial hypertension/reduced cerebral perfusion or administration of phenylephrine. Regional cerebral oxygen saturation decreased with the change to prone position and further decreased upon intrathecal injection. Cerebral near-infrared spectroscopy has a potential role to monitor the adequacy of cerebral perfusion and guide adjustment of systemic blood pressure during PPM. The authors have no conflicts of interest to disclose. Address correspondence to: Tasha L. Welch, MD. E-mail: welch.tasha@mayo.edu. Received May 14, 2019 Accepted August 20, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved Power and Challenges of Big Data: Why Clinical Researchers Should Not Be Ignored No abstract available Recent Preoperative Concussion and Postoperative Complications: A Retrospective Matched-cohort Study Background: Physiological alterations during the perianesthetic period may contribute to secondary neurocognitive injury after a concussion. Methods: Patients exposed to concussion and who received an anesthetic within 90 days were matched to unexposed patients without concussion. Intraoperative and postoperative events were compared. Subgroup analyses assessed relationships among patients with a concussion in the prior 30, 31 to 60, and 61 to 90 days and their respective unexposed matches. To facilitate identification of potential targets for further investigation, statistical comparisons are reported before, as well as after, correction for multiple comparisons. Results: Sixty concussion patients were matched to 176 unexposed patients. Before correction, 28.3% postconcussion versus 14.8% unexposed patients reported postanesthesia care unit pain score≥7 (P=0.02); 16.7% concussion versus 6.5% unexposed patients reported headache within 90 days of anesthesia (P=0.02) and 23.5% of patients who received surgery and anesthesia within 30 days of concussion experienced headache within 90 days of anesthesia compared with 7.1% in the unexposed group (P=0.01). Patients who experienced concussion and had anesthesia between 31 and 60 days after injury had a postanesthesia care unit Richmond Agitation and Sedation Scale score of −1.61±1.29 versus a score of −0.2±0.45 in unexposed patients (P=0.002). After adjusting the P-value threshold for multiple comparisons, the P-value for significance was instead 0.0016 for the overall cohort. Our study revealed no significant associations with application of adjusted significance thresholds. Conclusions: There were no differences in intraoperative and postoperative outcomes in patients with recent concussion compared with unexposed patients. Before correction for multiple comparisons, several potential targets for further investigation are identified. Well-powered studies are warranted. Presented in abstract form at the Annual Meeting of the Society for Neuroscience in Anesthesiology and Critical Care in San Francisco, CA, October 12, 2018. The authors have no funding or conflicts of interest to disclose. Address correspondence to: Arnoley S. Abcejo, MD. E-mail: abcejo.arnoley@mayo.edu. Received March 5, 2019 Accepted September 19, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved Intraoperative Magnetic Resonance Imaging–induced Oropharyngeal Thermal Injury in a Patient With Acromegaly No abstract available

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Projets actuels de télémédecine dans le domaine du diabète Focus sur les projets de télésuivi 2.0 et sur l'expérience strasbourgeoise à travers le projet DIABETe Emmanuel Andrès, Laurent Meyer, Abrar-Ahmad Zulfiqar, Mohamed Hajjam, Samy Talha, Sylvie Ervé, Jawad Hajjam, Jean Doucet, Nathalie Jeandidier, Amir Hajjam El Hassani Il a été démontré que le contrôle intensif de la glycémie retarde ou prévient le développement de complications micro- et macrovasculaires liées au diabète. Toutefois, on estime que 43,2 à 55,6 % des adultes atteints de diabète de type 2 n'atteignent pas la cible de référence pour le contrôle glycémique (hémoglobine glyquée [HbA1c] < 7,0 %). En pratique, les principales causes de détérioration du diabète nécessitant une intervention médicale sont liées [...] » Lire la suite

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

08:43

Performative Compliance and the State–Corporate Structuring of Neglect in a Residential Care Home for Older People Abstract The abuse and neglect of older people in care homes is widespread across England, but current causative explanations are limited and frequently fail to highlight the economic and political factors underpinning poor care. Informed by social harm and state–corporate crime perspectives, this study uses ethnographic data gathered through a nine-month period of working in an older person's residential care home to show how neglect is embedded in working routines. Three aspects of care are interrogated to reveal the embedded nature of harm in the home; all reveal the rift between official, regulatory rules and informal working practices shaped by material constraints of the labor process. This article explores the role of regulatory regimes in actively legitimizing sectors, such as the residential care industry, even in the face of routine violence, by bureaucratically ensuring the appearance of compliance with formal rules. While the harms of contemporary institutionalized care for older people have its roots in material conditions, performative compliance through regulation guarantees that these injurious outcomes are concealed. This article contends that malpractice (and harm) can be explained with reference to conjoint state–corporate relationships and practices. Valeria Vegh Weis: Marxism and Criminology: A History of Criminal Selectivity The Electronic Monitoring of Offenders in Context: From Policy to Political Logics Abstract The electronic monitoring (EM) of offenders is a subject that has been researched widely within criminology. Theoretical engagement with this instrument has been limited, however. The criminological literature, in fact, has focused primarily on empirical assessments of EM's financial and technical aspects, as well as on the legal implications of EM and its impact on reoffending. Against this backdrop, this article provides a critical examination of EM, focussing on how policy construes this penal measure, using Scotland as an example. In addition, drawing on Foucault's notion of governmentality, this article explores and problematizes the political logics (neoliberal, nationalist and techno-communitarian) which inform EM policy in the context of Scotland. The final section shifts the focus from exposing the political milieu within which EM policy emerges to contesting its possible effects, thereby extending the political critique of EM policy. The overarching aim is to contribute toward a nuanced political assessment of EM, while presenting directions for future engagement with this subject. Systemic Endangerment: A Tale of Neoliberal "Slumcare" Abstract In this case study of neoliberal responsibilization (Garland 1996), I used grounded theory methods to explore practitioners' experiences of Therapeutic Crisis Intervention at a for-profit, violence-prevention, group home for troubled youth. While previous research has shown that responsibilization can create spaces for on-the-ground resistance to post-welfarism and the reemergence of rehabilitative practices, this study shows that it can also lead to irresponsibly dangerous practices. As a result of this analysis, I introduce the concept of "slumcare" to capture a broad array of egregiously substandard behavioral-healthcare interventions that are provided throughout the United States in the name of crime prevention. While systemic endangerment is just one illustration of "slumcare," I contend that three interrelated processes—priority corruption, a paper trail of propriety, and the evasion of criticism—explain how the neoliberal state enables a host of "slumcare practices"—including systemic endangerment—to persist beyond the walls of this particular site. Governance Through Diversion in Neoliberal Times and the Possibilities for Transformative Social Justice Abstract Over the last decade, the dramatic increase in the number of young people diverted from formal processing through the youth justice system in England and Wales, and the equally sharp drop in the rate of youth custody suggest that the neoliberal formula for the penal governance of young people who offend has been undergoing significant reshaping. This article draws on research which interrogates the changes that are currently taking place, particularly the proliferation of "out of court" community-based measures of diversion and offense resolution, to develop a more fine-tuned conceptualization of the complexities of neoliberal youth penality. We base our findings principally on England and Wales, although it is likely that our analysis is applicable in other settings. With the extensive reduction in the capacity of the state to exert direct measures of institutional and community-based coercion, we seek to identify other, less overt processes that also aspire to maintain order and reproduce social relations favorable to the neoliberal project. In lieu of ending on a purely pessimistic note, we conclude with a brief outline of the potential for alternative, progressive strategies that seek to challenge rather than simply modify or incorporate previous modes of regulation and control. How Contemporary Rehabilitation Fails Youth and Sabotages the American Juvenile Justice System: A Critique and Call for Change Abstract Long a cornerstone of the American juvenile justice system, the idea that youth can change, and merit chances to do so, has enjoyed new life after decades of punitive erosion. Unfortunately, the rehabilitation offered to youth is largely shortsighted and inadequate. In this article, I argue that the juvenile justice system embraces a "myopic model" of rehabilitation that loses touch with the social roots of youth problems and focuses too heavily on improving internal thoughts and behaviors through short-term "pills and programs" (Goshe 2019). By losing sight of the societal harms at the root of delinquent behaviors, the myopic model advances a limited and ultimately unsustainable model of change. In contrast, this article contends that robust rehabilitation treats the social and the personal as crucial to the rehabilitative equation and offers a pathway to meaningful change for youth and the juvenile justice system. Challenging the Logics of Reformism and Humanism in Juvenile Justice Rhetoric Abstract This article draws on contemporary policy discourse in order to advance claims about the intractable figure of the "bad" child in contemporary juvenile justice reforms in the United States (US). The article focuses in particular on the discourses of trauma and "brain science" to point to a form of neo-positivism that has arguably emerged and which challenges efforts to engage in systematic decarceration. The article also focuses on the idea of the "bad child" that persists in the commitment of some reformers to the necessity of confinement for some children. The article questions the extent to which new forms of positivism challenge our ability to leverage structural claims. Young People, Shadow Carceral Innovations, and the Reproduction of Inequality Abstract The rate of detention for juveniles in the United States (US) is half what it was 20 years ago, and arrest rates have declined as well. Scholars, however, have illuminated more subtle processes of criminalization, such as through school disciplinary practices and civil penalties for low-level infractions in the community. Recognizing the presence and importance of such "shadow measures" helps us to understand how the carceral state penetrates deeper into the lives of (young) people, even in the midst of emerging reforms that would seem to dull the sharpest edges of the US criminal justice system. In this article, we delineate some of the ways that "shadow measures" help to sustain and legitimate deep economic, social, and justice system inequalities in the present-day US. Specifically, we describe how several "shadow carceral innovations" in the school and community mark some young people as "dangerous," "high-risk," or "unsafe," and show how these experiences are measured and judged across a variety of institutions. Ultimately, we argue that these "shadow measures" structure the day-to-day lives of youth outside the workforce and the cellblock, functioning as a key mechanism for maintaining inequality in the second decade of this century. Illicit Drug Markets, Consumer Capitalism and the Rise of Social Media: A Toxic Trap for Young People Abstract This article explores young people's involvement in illicit drug markets in England. It focuses in particular on why young people become involved in illicit drug distribution, the extent to which their involvement is predicated on adults' use of threats and violence, and how young people frame the morality of drug dealing. The article's findings are based on a unique dataset generated by a six-month period of online social media platform analysis, alongside additional data drawn from periods of observation, focus groups and interviews with young people and professionals. In short, I argue that drug prohibition, consumer capitalism, severe levels of inequality, and emerging problems associated with the rise of online social media are combining to produce a toxic trap that is dragging tens of thousands of young people into street-level drug dealing. Considered in this context, the inadequacy of the UK government's response to some of the main harms associated with illicit drug markets is clear: children and young people will continue to be coerced and exploited until either drug markets are legalized and regulated, or they have realistic opportunities to pursue lives that offer genuine meaning, decent levels of income, and levels of status and respect that are comparable to those provided by drug distribution.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

08:37

Distinct evolution of toll-like receptor signaling pathway genes in cetaceans AbstractBackground The relatively rapid spread and diversity of marine pathogens posed an initial and ongoing challenge for cetaceans (whales, dolphins, and porpoises), descendants of terrestrial mammals that transitioned from land to sea approximately 56 million years ago. Toll-like receptors (TLRs) play important roles in regulating immunity against pathogen infections by detecting specific molecular patterns and activating a wide range of downstream signaling pathways. The ever-increasing catalogue of mammalian genomes offers unprecedented opportunities to reveal genetic changes associated with evolutionary and ecological processes.Objective This study aimed to explore the molecular evolution of TLR signaling pathway genes in cetaceans.Methods Genes involved in the TLR signaling pathway were retrieved by BLAST searches using human coding sequences as queries. We tested each gene for positive selection along the cetacean branches using PAML and Hyphy. Physicochemical property changes of amino acids at all positively selected residues were assessed by TreeSAAP and visualized with WebLogo. Bovine and dolphin TLR4 was assessed using human embryonic kidney cell line HEK293, which lacks TLR4 and its co-receptor MD-2.Results We demonstrate that eight TLR signaling pathway genes are under positive selection in cetaceans. These include key genes in the response to Gram-negative bacteria: TLR4, CD14, and LY96 (MD-2). Moreover, 41 out of 65 positively selected sites were inferred to harbor substitution that dramatically changes the physicochemical properties of amino acids, with most of them situated in or adjacent to functional regions. We also found strong evidence that positive selection occurred in the lineage of the Yangtze finless porpoise, likely reflecting relatively recent adaptions to a freshwater milieu. Species-specific differences in TLR4 response were observed between cetacean and terrestrial species. Cetacean TLR4 was significantly less responsive to lipopolysaccharides from a terrestrial E. coli strain, possibly a reflection of the arms race of host–pathogen co-evolution faced by cetaceans in an aquatic environment.Conclusion This study provides further impetus for studies on the evolution and function of the cetacean immune system. A thiosemicarbazone derivative induces triple negative breast cancer cell apoptosis: possible role of miRNA-125a-5p and miRNA-181a-5p AbstractBackground Breast cancer, the most commonly diagnosed malignancy in women, accounts for the highest cancer-related deaths worldwide. Triple negative breast cancer (TNBC), lacking the expression of estrogen, progesterone and HER2 receptors, has an aggressive clinical phenotype and is susceptible to chemotherapy but not to hormonal or targeted immunotherapy. In an attempt to identify potent and selective anti-TNBC agents, a set of thiosemicarbazone derivatives were screened for their cytotoxic activity against MDA-MB 231 breast cancer cell line.Methods MTT assay was used to examine cell viability. P53 phosphorylation status, poly (ADP-ribose) polymerase (PARP) cleavage as well as Bcl2 and Bax protein levels were assessed by Western blot. Quantitative Real Time-PCR was carried out to characterize miRNAs expression levels.Results Combining Cisplatin + thiosemicarbazone compound 4 showed potent anti-TNBC potential. Cisplatin + compound 4 significantly enhanced p53 phosphorylation, induced Bax amount, reduced Bcl2 protein levels, enhanced PARP cleavage and modulated miRNAs expression profile in TNBCs, with a particular overexpression of miR-125a-5p and miR-181a-5p. Intriguingly, miR-125a-5p and miR-181a-5p could significantly downregulate BCL2 expression by binding to their target sites in the 3′UTR.Conclusions Collectively, our results demonstrate an anti-TNBC activity of Cisplatin + thiosemicarbazone compound 4 combination mediated via induction of apoptosis. Transcriptome analysis to characterize the genes related to gonad growth and fatty acid metabolism in the sea urchin Strongylocentrotus intermedius AbstractBackground Sea urchin gonads of both sexes, commonly termed "roe", are highly valued seafood delicacies, and Strongylocentrotus intermedius is considered one of the tastiest sea urchins. In order to produce high-quality gonads for consumption and clarify the mechanism of gonad growth and development of the sea urchin, more genetic information, especially at the transcriptome level, is needed.Objective A more thorough understanding of sea urchin gonad growth and development in both sexes could enable regulation of these processes at several stages with the aim of suppressing gametogenesis in order to produce high-quality gonads for consumption.Methods The adult sea urchins S. intermedius were cultured for 3 months, and were sampled for the gonadal transcriptome analysis which has been performed on the RNAs of three male and female adults of S. intermedius in each gonad development stage.Results Illumina sequencing raw sequence data was deposited in the NCBI Sequence Read Archive (SRA) database (PRJNA532998). It generated 560,196,356 raw reads and 548,956,944 clean reads were acquired, which were assembled into 107,850 transcripts with 44,124 genes. Comparative analysis showed the differentially expressed genes (DEGs) from 114 to 2566. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to determine the functional significance of these DEGs. We have selected 9 genes related to growth and 12 genes related to fatty acid biosynthesis and metabolism in sea urchin gonads.Conclusion These data for sea urchins were intended to provide markers for gonad growth and development that can be accumulated for use in aquaculture applications. Study on the differential gene expression of elm leaves fed on by Tetraneura akinire Sasaki AbstractBackground To study the essential molecular mechanism of gall formation is very important.Objective To investigate the differential gene expression in leaves fed on by Tetraneura akinire Sasaki and to provide a basis for the better understanding of the essential molecular mechanism of gall formation.Methods The infected leaves of the elm were divided into three periods: initial formation period (T2), growth and differentiation period (T3), and cracking period (T4). The untouched leaves were used as the control (T1). RNA-Seq was performed, and the high-quality sequences were mapped to the reference genome and the elm gene database to obtain the gene expression profiles. The expression level of each gene was calculated by the RPKM method. A combination of FDR ≤ 0.01 and the absolute value of |log2 ratio (T/CK)| ≥ 2 was used as the threshold to determine the significance of gene expression. Finally, GO and pathway enrichment analyses were used to identify the significantly enriched functional classification and metabolic pathways in DEGs.Results The results revealed that approximately 244 mRNAs were detected between T1 and T2, including 192 up-regulated and 52 down-regulated mRNAs; approximately 175 mRNAs were detected between T1 and T3, including 145 up-regulated and 30 down-regulated mRNAs; and approximately 372 mRNAs were detected between T1 and T4, including 360 up-regulated and 12 down-regulated mRNAs. Approximately 34 differentially expressed genes were identified by Venn analysis. Comparing the three infection periods to the control, there were 28 up-regulated and six down-regulated mRNAs. Additionally, 562 genes were used for cluster analysis, which revealed that the gene expression in T2 and T3 changed greatly. Genes related to cell proliferation and respiration, such as microtubulin and 6-phosphoric acid fructose kinase were mainly up-regulated during the T2 period. Genes encoding lipoxygenase, glutathione-S-transferase, superoxide dismutase and protease inhibitor were up-regulated during T2 and T3. Genes encoding lignocellulose synthase were up-regulated during T4, which suggests the reinforcement of the cell wall to improve the resistance to the damage of the Tetraneura akinire Sasaki.Conclusions The results showed that the feeding of Tetraneura akinire Sasaki caused the differential expression of elm genes and influenced cellular energy metabolism. These changes in physiological response and gene expression of the elm compose the physiological and molecular basis of the gall formation and may improve the resistance of elm to Tetraneura akinire Sasaki. A core set of microsatellite loci for yellow-throated marten, Martes flavigula : a case of inferences of family relationships AbstractBackground Microsatellite markers are an ideal molecular marker for population genetic studies such as population structure, pedigree, and kinship. The yellow-throated marten (Martes flavigula) is widely distributed in coniferous and deciduous forests of eastern Asia and plays the role of an indicator and umbrella species in South Korea, given the absence of top predators such as tiger and leopard.Objective The aim of our study was to establish a core set of microsatellite markers that could be used for a population genetics study on M. flavigula.Methods We characterized 21 di-motif microsatellites for M. flavigula by Illumina next-generation sequencing. We evaluated them for a population genetics study against five established criteria together with 33 previously developed microsatellites. We calculated relatedness values between individual yellow-throated martens in two groups that were suspected to be siblings using the selected core set of markers to confirm applicability.Results Twenty-three loci were determined as the core set of microsatellite markers. The probability of identity P(ID) and probability of identity between siblings P(ID)sib of the core set was estimated as 2−15 and 2.2−7, respectively. Relatedness values between individuals in the two groups of M. flavigula revealed that one of the pairs was sisters, confirming that the core set can be applied to kinship studies.Conclusion The developed microsatellite core set in this study is expected to contribute to studies on molecular ecology and population structure of M. flavigula. Comparative transcript profiling and cytological observation of the newly bred recessive genic male sterility non-heading Chinese cabbage ( Brassica rapa ssp. chinensis) line WS24-3A AbstractBackground WS24-3A is a newly bred non-heading Chinese cabbage genic male-sterile line, in which sterility is controlled by a recessive gene, designated as Bra2ms. WS24-3A has been used for hybrid breeding.Objective To reveal the underlying molecular mechanisms responsible for the sterility of WS24-3A.Methods Cytological observation of the process of sterile/fertile anther development was performed to determine the tissue and stage in which sterility occurs. Phenotyping and transcriptomic analyses were performed to identify differentially expressed genes (DEGs) between sterile and fertile flower buds at different stages.Results Cytological analysis revealed no tetrads at stage 7 or at later stages of anther development, and the degradation of callose was delayed. Abnormal meiocytes were surrounded by sustaining callose that degenerated gradually in WS24-3A. Comparative transcript profiling identified 3282 DEGs during three anther developmental stages, namely, pre-meiotic anther, meiotic anther, and anthers with single-celled pollen stage. The difference in DEG percentage between up-regulated and down-regulated at meiotic anther stage was obviously larger than at the other two stages; further, most DEGs are important for male meiosis, callose synthesis and dissolution, and tapetum development. Ten DEGs were found to be involved in anther and pollen development, which were analyzed by quantitative PCR.Conclusion Bra2ms affected gene expression in meiocytes and associated with callose synthesis, degradation and tapetum development. Our results provide clues to elucidate the molecular mechanism of genic male sterility in non-heading Chinese cabbage. A transcriptome analysis uncovers Panax notoginseng resistance to Fusarium solani induced by methyl jasmonate AbstractBackground Panax notoginseng is a famous Chinese herbal medicine, but the root rot disease mainly caused by Fusarium solani severely reduces the yield and quality of its medicinal materials.Objective The defense priming in P. notoginseng through exogenous application of signaling molecule will supply theoretical support for the exogenous regulation of disease resistance in P. notoginseng.Methods In this study, the exogenous application of methyl jasmonate (MeJA) increased P. notoginseng's resistance to F. solani. Furthermore, the P. notoginseng transcriptome during F. solani infection was investigated through next-generation sequencing to uncover the resistance mechanism of P. notogingseng induced by MeJA.Results The de novo assembly of transcriptome sequences produced 80,551 unigenes, and 36,771 of these unigenes were annotated by at least one database. A differentially expressed gene analysis revealed that a large number of genes related to terpenoid backbone biosynthesis, phenylalanine metabolism, and plant–pathogen interactions were predominantly up-regulated by MeJA. Moreover, jasmonic acid (JA) biosynthesis-related genes and the JA signaling pathway genes, such as linoleate 13S-lipoxygenase, allene oxide cyclase, allene oxide synthase, TIFY, defensin, and pathogenesis-related proteins, showed increased transcriptional levels after inoculation with F. solani. Notably, according to the gene expression analysis, JA and ethylene signaling pathways may act synergistically to positively regulate the defense responses of P. notoginseng to F. solani.Conclusion JA signaling appears to play a vital role in P. notoginseng responses to F. solani infection, which will be helpful in improving the disease resistance of P. notoginseng cultivars as well as in developing an environmentally friendly biological control method for root rot disease. Up-regulation of miR-27 extenuates lipopolysaccharide-induced injury in H9c2 cells via modulating ICAM1 expression AbstractBackground MiR-27 has been found to present an overt myocardial expression during cardiogenesis. However, whether miR-27 involves in myocarditis development and the possible molecular mechanism remain unknown. The purpose of this study was to investigate the biological characteristic of miR-27 in LPS-damaged H9c2 cells.Methods H9c2 cells were treated with lipopolysaccharide (LPS, 10 µg/ml) for 12 h to form cell injury. MiR-27 mimic and inhibitor were used to up-regulate or down-regulate miR-27 expression. MTT assay and flow cytometry analysis were conducted to test cell viability and apoptosis. The relative RNA expression level of miR-27 and intercellular adhesion molecule 1 (ICAM1) was determined by qRT-PCR. Luciferase reporter gene assay was utilized to confirm the interaction between miR-27 and ICAM1. Western blot was used to determine the protein expression levels.Results We observed that LPS treatment significantly decreased the level of miR-27 in H9c2 cells. Moreover, LPS exposure suppressed cell viability, promoted cell apoptosis and increased the relative expression of p-NF-κB p65/NF-κB p65 and p-IκBα/IκBα. Up-regulation of miR-27 increased cell proliferation and reduced cell apoptosis, while down-regulation of miR-27 suppressed cell growth and promoted cell apoptosis. ICAM1 was predicted and verified as a target of miR-27, and the expression of ICAM1 is negatively regulated by miR-27. The relative expression of p-NF-κB p65/NF-κB p65 and p-IκBα/IκBα was dramatically decreased by miR-27 mimic and increased by miR-27 inhibitor.Conclusion Our study illustrated that up-regulation of miR-27 exhibits a protective effect on LPS-damaged H9c2 cells, which may be achieved by regulating ICAM1 and NF-κB signaling. Integrated analysis of quantitative proteome and transcriptional profiles reveals abnormal gene expression and signal pathway in bladder cancer AbstractBackground Bladder cancer (BCa) is a tumor associated with high morbidity and mortality and its incidence is increasing worldwide. However, the pathogenesis of bladder cancer is not well understood.Objective To further illustrate the molecular mechanisms involved in the pathogenesis of BCa and identify potential therapeutic targets, we combined the transcriptomic analysis with RNA sequencing and tandem mass tags (TMT)-based proteomic methods to quantitatively screen the differentially expressed genes and proteins between bladder cancer tissues (BC) and adjacent normal tissues (AN).Results Transcriptome and proteome studies indicated 7094 differentially expressed genes (DEGs) and 596 differentially expressed proteins (DEPs) between BC and AN, respectively. GO enrichment analyses revealed that cell adhesion, calcium ion transport, and regulation of ATPase activity were highly enriched in BCa. Moreover, several key signaling pathway were identified as of relevance to BCa, in particular the ECM-receptor interaction, cell adhesion molecules (CAMs), and PPAR signaling pathway. Interestingly, 367 genes were shared by DEGs and DEPs, and a significant positive correlation between mRNA and translation profiles was found.Conclusion In summary, this joint analysis of transcript and protein profiles provides a comprehensive reference map of gene activity regarding the disease status of BCa. Analysis of differential gene expression in cold-tolerant vs. cold-sensitive varieties of snap bean ( Phaseolus vulgaris L.) in response to low temperature stress AbstractBackground Snap bean, Phaseolus vulgaris L., as a warm-season vegetable, low temperature stress seriously affect the yield and quality. At present, little is known about the genes and molecular regulation mechanism in cold response in snap bean exposed to low temperature.Objectives Our objectives were to identify the low temperature response genes in snap bean and to examine differences in the gene response between cold-tolerant and cold-sensitive genotypes.Methods We used two highly inbred snap bean lines in this study, the cold-tolerant line '120', and the cold-sensitive line '093'. The plants were grown to the three leaf and one heart stage and exposed to 4 °C low temperature. We used RNA sequencing (RNA-seq) to analyze the differences of gene expression.Results 988 and 874 cold-responsive genes were identified in 'T120 vs CK120' and 'T093 vs CK093' ('T' stands for low temperature treatment, and 'CK' stands for control at room temperature), respectively. Of these, 555 and 442 genes were unique to cold-stressed lines '120' and '093', respectively compared to the control. Our analysis of these differentially expressed genes indicates that Ca2+, ROS, and hormones act as signaling molecules that play important roles in low temperature response in P. vulgaris. Altering the expression of genes in these signaling pathways activates expression of downstream response genes which can interact with other signaling regulatory networks. This may maintained the balance of ROS and hormones, making line '120' more cold-tolerant than line '093'.Conclusion Our results provide a preliminarily understanding of the molecular basis of low temperature response in snap bean, and also establish a foundation for the future genetic improvement of cold sensitivity in snap bean by incorporating genes for cold tolerance.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

08:36

Emodin Attenuates Severe Acute Pancreatitis via Antioxidant and Anti-inflammatory Activity Abstract There is no specific drug to treat severe acute pancreatitis (SAP), which induces substantial medical and social burden. Many studies have reported the beneficial effects of emodin against SAP in vivo and in vitro. However, the underlying mechanism has been unclear. This paper described the design and implementation of anti-inflammatory and antioxidant activity of emodin. Emodin restored the pathological damage of SAP and simultaneously decreased the high levels of serum amylase, lipase, TNF-α, and IL-18 in the peripheral blood of SAP rat. Emodin reversed reactive oxygen species (ROS) in neutrophils derived from SAP rat. The levels of voltage-dependent anion channel 1 (VDAC1), NOD-like receptor protein 3 (NLRP3), caspase-1, and IL-18 were examined to analyze the change of inflammasome-related mediators between SAP and emodin treatment. These findings suggest that emodin plays its protective role on SAP against oxidative stress and inflammasome signals. Characterization of Circular RNA and microRNA Profiles in Septic Myocardial Depression: a Lipopolysaccharide-Induced Rat Septic Shock Model Abstract Septic shock with heart dysfunction is common in intensive care units. However, the mechanism underlying myocardial depression is still unclear. Whether circular RNA (circRNA) or microRNA (miRNA) profiles differ between patients with and without myocardial depression is unknown. We generated a hypodynamic septic shock model induced by lipopolysaccharide (LPS) in adolescent rats. A total of 12 rats were utilized and heart tissue from each was collected. RNA sequencing was performed on left ventricular tissue. We focused on features of circRNAs and miRNAs, predicting their function by bioinformatic analysis and constructing circRNA-associated and miRNA-associated regulatory networks in heart tissue. We detected 851 circRNAs in heart samples, and 11 showed differential expression. A total of 639 annotated miRNAs and 91 novel miRNAs were explored including 78 showing differential expression between the two groups. We then constructed the most comprehensive circRNA-associated and miRNA-associated networks to explore their regulatory relationship in septic heart tissue, and demonstrated that different networks could potentially participate in and regulate the pathological process of sepsis. Furthermore, gene ontology term enrichment indicated miRNAs, and miRNA-mRNA networks could be associated with regulation and metabolic process, or influence cellular functions. The construction of regulator networks could improve the understanding of the basic molecular mechanisms underlying myocardial depression. It will be important for future investigations to ascertain the biological mechanisms present during the development of sepsis-induced myocardial depression to influence approaches to treatment. Potential Anti-Inflammatory Effect of Escitalopram in Iodoacetamide-Induced Colitis in Depressed Ovariectomized Rats: Role of α7-nAChR Abstract Escitalopram, a drug of choice in the treatment of depression, was recently shown to possess an anti-inflammatory activity. The aim of the present study was to elucidate the effect of escitalopram on peripheral inflammatory cascades in iodoacetamide-induced colitis associated with depressive behavior in ovariectomized rats. Moreover, the role of α-7 nicotinic acetylcholine receptor in mediating the anti-colitic effect of escitalopram was examined using a nicotinic receptor antagonist methyllycaconitine citrate. Colitis was induced by intracolonic injection of 4% iodoacetamide in ovariectomized rats. Escitalopram (10 mg/kg/day, i.p.) was then injected for 1 week and several parameters including macroscopic (colon mass index and ulcerative area), microscopic (histopathology and scoring), and biochemical (myeloperoxidase and tumor necrosis factor-α) were determined. Colitis induction in ovariectomized rats resulted in a marked increase in colon mass index, ulcerative area, histopathological scoring, myeloperoxidase activity and tumor necrosis factor-α levels. These effects were ameliorated by escitalopram, even in the presence of methyllycaconitine indicating that α-7 nicotinic acetylcholine receptor does not mediate the anti-inflammatory effect of escitalopram. The present study revealed the beneficial effect of escitalopram in iodoacetamide induced colitis in ovariectomized rats and suggests that it may represent a new therapeutic agent for the treatment of inflammatory bowel disease, especially in patients with or at high risk of depressive behavior. Inhibition of Fibroblast Growth Factor Receptor by AZD4547 Protects Against Inflammation in Septic Mice Abstract Sepsis is a life-threatening condition caused by the dysregulated host immune response to infection characterized by excessive secretion of inflammatory factors. AZD4547 is a selective inhibitor of fibroblast growth factor receptors that participates in the inflammatory response. The aim of this study was to investigate the inflammation-targeting effects and related molecular mechanisms of AZD4547 in sepsis using a cecal ligation and puncture model and RAW264.7 macrophages stimulated with lipopolysaccharide. AZD4547 improved the survival of CLP mice and exhibited a robust protective function against lung damage histologically. Pretreatment with AZD4547 significantly alleviated the expression of the pro-inflammatory factors IL-1β, IL-6, TNF-α, MMP9, and CXCL10 both in vivo and in vitro. In addition, AZD4547 suppressed the proliferative activity of macrophages in lung tissue and RAW264.7 macrophages. In addition, the LPS-induced phosphorylation of key proteins of NF-κB/MAPK/STAT3 pathways in RAW264.7 macrophages, such as p65, IκB-α, Erk1/2, JNK, and STAT3 proteins, could be inhibited by AZD4547 pretreatment. In conclusion, AZD4547 exerts a protective effect against excessive inflammatory damage in septic mice and may have the potential for use as an effective drug for the management of sepsis. The Role of Decidual PD-1 + Treg Cells in Adverse Pregnancy Outcomes due to Toxoplasma gondii Infection Abstract Toxoplasma gondii infection during pregnancy can result in adverse pregnancy outcomes. Previously, we have reported that these outcomes are associated with the impaired function of decidual Treg cells; however, the detailed mechanisms involved were unclear. It has been reported that the suppressive capacity of Treg cells is dependent on PD-1 expression. The present study explored the role of decidual PD-1+ Treg cell function in adverse pregnancy outcomes due to T. gondii infection. Toxoplasma gondii–infected pregnant mice were sacrificed on gestational day 14 and their pregnancy outcomes were observed. The expression of PD-1 on decidual Treg cells and expressions of Foxp3, CTLA-4, TGF-β, and IL-10 on decidual PD-1+ and PD-1− Treg cells were determined using flow cytometry. The results showed that the expression of PD-1 on decidual Treg cells was clearly higher in the T. gondii–infected mice than in the normal mice. Meanwhile, the expressions of Foxp3, CTLA-4, TGF-β, and IL-10 on decidual PD-1+ Treg cells were higher in the infected mice than in the normal mice. The expressions were higher in decidual PD1+ Treg cells than in PD-1− Treg cells in the infected mice. However, these expressions on PD-1− Treg cells did not significantly differ between the infected and normal mice. Nonetheless, the absolute percentages of decidual PD-1+ Treg cells decreased significantly in the infected mice compared with those in the normal mice. These results suggest that T. gondii infection mainly influences the function of decidual PD-1+ Treg cells, which would result in an insufficiently immunotolerant microenvironment and consequently in adverse pregnancy outcomes. Damage and Phenotype Change in PC12 Cells Induced by Lipopolysaccharide Can Be Inhibited by Antioxidants Through Reduced Cytoskeleton Protein Synthesis Abstract The present study investigated changes in cellular phenotype and oxidative stress during the inflammatory response in PC12 cells stimulated by lipopolysaccharide (LPS) and assessed the effects of minocycline, astragalus (AST), and baicalin on inflammation. PC12 cells were exposed to LPS with or without minocycline, AST, or baicalin. Cell viability was measured by a thiazolyl blue tetrazolium bromide (MTT) assay. Contrast and laser confocal microscopy were used to analyze changes in cellular phenotype and cytoskeleton synthesis. Western blotting tested the expression of α7nAChR and vimentin. Inhibitory ratio of superoxide dismutase (SOD) activity and leakage of lactate dehydrogenase (LDH) were detected to evaluate cellular oxidative stress. Results showed that LPS could attenuate PC12 cell viability in a time- and dose-dependent manner, which could be rescued by minocycline. In addition, minocycline could reverse PC12 cell phenotypic change and the synthesis of the mesenchymal cytoskeleton protein vimentin, both induced by LPS. During LPS-initiated inflammation, α7nAChR and vimentin expression were obviously inhibited by minocycline, AST, or baicalin. The inhibitory rate of SOD activity and LDH leakage in PC12 cells were increased by LPS and attenuated significantly when exposed to minocycline, AST, or baicalin. These findings suggest phenotype change, altered cytoskeleton protein synthesis, and oxidative stress are all involved in the inflammatory response in PC12 cells during which α7 nicotinic acetylcholine receptor (α7nAChR) is induced by LPS stimulation. Minocycline, AST, and baicalin have a protective effect against PC12 cell injury, acting as antioxidants and inhibitors of mesenchymal proteins. Investigation of Extracellular Matrix Protein Expression Dynamics Using Murine Models of Systemic Inflammation Abstract Extracellular matrix (ECM) proteins form the structural support for migration of leukocytes and provide multiple signals to assist in their functions during inflammatory conditions. Presence of pro-inflammatory mediators in the tissues results in the remodelling of matrices which could modify the functions of extravasated leukocytes. Previous reports have shown changes in the expression of ECM proteins during local inflammatory responses. In this study, we have investigated the time- and tissue-specific expression profile of key ECM proteins in systemic inflammation using lipopolysaccharide (LPS)-induced endotoxemia and cecal ligation and puncture (CLP) mouse models. The results show that compared to naïve tissues, within 12 h following CLP surgery, a 20–30-fold increase was observed in the expression of collagen-IV (Col-IV) transcripts in the mesentery tissues with a 2.4-fold increase in the protein by 24 h. However, Western blot band intensities indicated that vimentin and fibrinogen were remarkably expressed in more quantity compared to Col-IV. Secondly, in CLP group of mice, fibrinogen showed 6–40-fold increase in mRNA level in various tissues with about 2-fold increase in the protein level compared to respective naïve tissues. Similar studies in the LPS-injected mice showed up to 2–3 fold increase in the expression of Col-IV, fibrinogen and vimentin at protein level in the lungs. In such animals, although similar pattern was observed for fibrinogen in kidney and liver tissues, the mesentery showed prominent changes in Col-IV and vimentin mRNA compared to CLP. Further, bioinformatics analysis showed multiple pathways which could be associated with vimentin, Col-IV and fibrinogen under inflammatory conditions both in human and mouse. The current study will help in better understanding of possible signalling from ECM proteins in inflammatory microenvironment and may contribute in development of cell adhesion-based therapeutics. Role of JNK Signaling Pathway in Dexmedetomidine Post-Conditioning-Induced Reduction of the Inflammatory Response and Autophagy Effect of Focal Cerebral Ischemia Reperfusion Injury in Rats Abstract To investigate the effect of dexmedetomidine post-conditioning on the inflammatory response and autophagy effect of focal cerebral ischemia reperfusion injury in rats, and further to study its potential mechanisms. Water maze was conducted to evaluate spatial learning and memory ability of middle cerebral artery occlusion (MCAO) rats. TTC staining was used to observe the area of cerebral infarction. The expressions of inflammatory factors in serum were detected by ELISA. TUNEL assay, HE staining, and transmission electron microscopy were used to detect the apoptosis of neurons, neuro-cytopathic changes, and the formation of auto-phagosome in hippocampus CA1 region, respectively. The mRNA and protein expression of Beclin-1, Caspase-3, and light chain 3 (LC3) were detected by qRT-PCR and Western blot. Moreover, the activity of C-Jun N-terminal kinase (JNK) pathway was detected by Western blot. The escape latency (EL); cerebral infarction area ratio; positive apoptosis; neuron pathological changes; auto-phagosome numbers; inflammatory factor contents; mRNA and protein expressions of Beclin-1, Caspase-3 and LC3II/I; and the phosphorylation level of JNK were decreased, while the times across platform and the times stayed in the quadrant of the original platform were increased after dexmedetomidine treatment. However, the protective effect of dexmedetomidine on brain injury in MCAO rats was reversed by JNK pathway activator. Dexmedetomidine post-conditioning could improve learning and memory dysfunction caused by MCAO in rats and reduce the inflammatory response and autophagy effect. The mechanism may be related to inhibition of JNK pathway activation. Pleural Effusion IL-33/sST2 Levels and Effects of Low and High IL-33/sST2 Levels on Human Mesothelial Cell Adhesion and Migration Abstract Interleukin 33 (IL-33) is an alarmin with multiple roles in immunity and cell homeostasis, highly expressed in barrier sites, acting via the suppression of tumorigenicity 2 receptor (ST2). Production of IL-33 and soluble ST2 (sST2), a decoy receptor for IL-33, has been implicated in several pulmonary diseases, but both have been scarcely investigated in pleural diseases. The aim of this study was to determine the levels of IL-33 and sST2 in transudative (TrPEs), malignant (MPEs), and parapneumonic (PPEs) pleural effusions (PEs) and investigate the effect of PE fluids from each group with low and high IL-33/sST2 levels on MeT-5A cell adhesion and migration. IL-33 and sST2 pleural fluid levels were similar among TrPEs, MPEs, and PPEs. However, a significant correlation was found between IL-33 and LDH and in sST2 levels with lymphocyte counts in TrPEs. Additionally, in MPEs the levels of IL-33 correlated with the levels of sST2 and with the red blood cell counts. Furthermore, incubation of MeT-5A cells with MPEs and PPEs bearing low or high levels of IL-33/sST2 yielded significant differential effects on MeT-5A cell adhesion and migration. In MPEs, high IL-33/sST2 levels led to increased adhesion and migration of MeT-5A cells, while in PPEs the effect was the opposite, while no effect in both cell phenotypes was determined for TrPEs. These results reveal a clinical context dependent effect of the IL-33/sST2 axis in PEs. Immunomodulatory and Anti-Inflammatory Potential of Curcumin for the Treatment of Allergic Asthma: Effects on Expression Levels of Pro-inflammatory Cytokines and Aquaporins Abstract Curcumin is well known for possessing anti-inflammatory properties and for its beneficial effects in the treatment of asthma. Current study investigates the immunomodulatory and anti-inflammatory effects of curcumin using mouse model of ovalbumin-induced allergic asthma. BALB/c mice were immunized with ovalbumin on day 0 and 14 to induce allergic asthma. Animals were treated with two different doses of curcumin (20 mg/kg and 100 mg/kg) and methylprednisolone from day 21 to 28. Mice were also daily challenged intranasally with ovalbumin during treatment period, and all groups were sacrificed at day 28. Histopathological examination showed amelioration of allergic asthma in treated groups as evident by the attenuation of infiltration of inflammatory cells, goblet cell hyperplasia, alveolar thickening, and edema and vascular congestion. Curcumin significantly reduced total and differential leukocyte counts in both bronchoalveolar lavage fluid and blood. Reverse transcription polymerase chain reaction analysis showed significantly suppressed mRNA expression levels of IL-4 and IL-5 (pro-inflammatory cytokines), TNF-α, TGF-β (pro-fibrotic cytokines), eotaxin (chemokine), and heat shock protein 70 (marker of airway obstruction) in treated groups. Attenuation of these pro-inflammatory markers might have led to the suppression of airway inflammation. The expression levels of aquaporin-1 (AQP) and AQP-5 were found significantly elevated in experimental groups which might be responsible for reduction of pulmonary edema. In conclusion, curcumin significantly ameliorated allergic asthma. The anti-asthmatic effect might be attributed to the suppression of pro-inflammatory cytokines, and elevation of aquaporin expression levels, suggesting further studies and clinical trials to establish its candidature in the treatment of allergic asthma.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

08:36

Response to the comments made by Möller, P., E. Rosenthal, E. and Siebert, C. to the paper "The Sdom evaporite formation in Israel and its relationship with the Messinian Salinity Crisis" by J. Charrach Abstract I thank the discussors for their critique of the above paper. In geology there are rarely any absolute models but working hypotheses, which will be modified with new data. The paper under discussion, Charrach (Carbonates Evaporites 33:727–766, 2018a), presents a very new large data set, which is multi-disciplinary and integrated the most recent research. The critique by Möller et al. (Carbonates Evaporites https://doi.org/10.1007/s13146-019-00486-3, 2019) and their paper of 2018 (Int J Earth Sci 107:2409–2431, 2018), presents a computer simulation, which must be validated with field evidence and recent research in the area, and not based on assumptions, which have turned into facts over time. The discussors may be unfamiliar with the geological research that has been published over the last 20 years in the areas under consideration. Furthermore, the research on marine–non-marine evaporite formations is hardly considered in their discussion, yet much has been published. Comments on "The Sdom evaporite formation in Israel and its relationship with the Messinian Salinity Crisis" by J. Charrach Abstract According to J. Charrach, the Sdom formation is a major non-marine evaporite sequence deposited during the climax of the Mediterranean Salinity Crisis (MSC). Hydrochemical studies, however, reveal that the evaporites of the Sdom and Zemah stratigraphic columns dominantly originate from evaporated Tethys seawater mixed with some local drainage water. The formation of evaporites in the northern and southern Inland Sea lasted about 2 Ma, a period that could only be pre-Messinian, i.e., most probably Tortonian. Introductory editorial Abstract In order to understand the genesis of a carbonate (karst) aquifer from its initial stage to a fully developed karst system number of different methods have been developed over the last 50 years. Nevertheless, with the continued progress of new technologies developing, the groundwater genesis of the karst aquifer becoming more and more precisely defined. Still, more investigation, specific forums and scientific discussion as well as publications are necessary to improve the knowledge of groundwater genesis within carbonate aquifers, as a main step of karst groundwater protection and utilization. With increasing demands on water resources protection, water supply, urbanisation, construction of large dams, reservoirs, tunnels, railways, roads, mines, tailings and waste disposal structures also increase necessity for close co-operation of a wide spectrum of scientist in precise defining and modeling of groundwater genesis. Groundwater from carbonate aquifer as a rule have good physic-chemical characteristics, and inside of the carbonate rocks can accumulate a large quantities of groundwater, which are ideal for watersupply. On the other hand, they are characterized with high vulnerability to pollution, due to weak autopurification properties of the medium, and big variation in discharging. In order of properly using of karst natural resources, the good knowledge of the hydrogeological system genesis is necessary, meaning primarily on carbonate or evaporitic formation with well-developed dissolution porosity. In a case of defining of groundwater genesis of carbonat aquifer as well as protection, a large number of methodological approaches can be applied in order to define the recharge zone and connection between the underground and surface waters, the mean residence time, as well as groundwater interaction with the hostrock, which have influence on chemical composition and temperature regime of discharged water. This special thematic edition partly includes extended versions of the selected papers that will have been presented at the International Symposium KARST 2018, which deals with the above presented and discussed topics precisely through the works of a large number of world-renowned authors. A number of papers will be presented by invitation, and will directly refer to specific areas of karst exploration: hydrogeology, geomorphology, engineering geology, speleology, all relating to the sustainable use of karst waters as an essential natural resource. The papers will cover a wide range of recent scientific research that was carried out in karst terrains all over the world (China, USA, Canada, Russia, Iran, Peru, Turkey, Malaysia and many European countries). Microfacies and depositional environments of the Qom Formation in Barzok area, SW Kashan, Iran Abstract Qom Formation (Oligo-Miocene marine deposits of Middle Iran) in the southwestern Kashan was studied to determine its microfacies and depositional environments. Outcrops of the Qom Formation in the study area with 410 m, consist mainly of limestone, sandy limestone, shale and marl. Study section is unconformably underlain by the Eocene volcanic rocks and overlain by alluvium. Biogenic components of the Qom Formation comprise mainly of larger benthic foraminifera, coralline red algae and corals. Based on the presence of Nummulites spp. (Nummulites fichteli, Nummulites vascus, Nummulites cf. vascus, Nummulites sp.) throughout the study section, the Qom Formation is considered to be Rupelian in age. Microfacies analysis and field investigations on the study section led to recognition of six carbonate microfacies and two marl and shale facies. Two major depositional environments were identified in the study area including lagoon and open marine. Based on the recognized microfacies and field investigations, deposition of the Qom Formation in Barzok area took place on a carbonate ramp; besides, most of the carbonate parts of the study section are deposited in the open-marine settings. The high abundance of larger benthic foraminifera, coralline red algae and corals indicates that deposition took place in the tropical warm waters. Delineation of groundwater potential zones using remote sensing (RS), geographical information system (GIS) and analytic hierarchy process (AHP) techniques: a case study in the Leylia–Keynow watershed, southwest of Iran Abstract In this research, a standard methodology has been applied to delineate groundwater resource potential zonation based on integrated remote sensing (RS), geographic information system (GIS), and analytical hierarchy process (AHP) techniques in Leylia–Keynow watershed, southwest of Iran. A total of five sets of criteria/factors (including lineament density, rainfall, lithology, slope, and drainage density) believed to be influencing groundwater storage potential in the area were selected. Each criterion/factor was assigned appropriate weight based on Saaty's 9-point scale and the weights were normalized through the analytic hierarchy process (AHP). The process was integrated in the GIS environment to produce the groundwater potential prediction map for the area. The fi9-p groundwater prospect map obtained was classified as excellent potential, very good potential, good potential, moderate potential, and poor potential zone. The obtained results indicated that only 21% (122 km2) of the study area exhibit poor groundwater potential, whereas most of the regions (326 km2) in the research showed good to excellent groundwater potential. Also, about 24% (141 km2) was classified as having moderate groundwater potential. The good to excellent potential zones are characterized by the higher lineament density, higher rainfall, and lithology type such as limestone, whereas the poor to moderate groundwater potential zones are characterized by the lesser lineament density, lower rainfall, lithology type of shale and marl as well as shale and limestone. Based on the obtained evidences, the tectonic structures had an important role in fracturing and crushing of limestone units in the area and so are vital for karst and ground water sources development. The demarcation of groundwater potential zones in the Leylia–Keynow watershed will be helpful for future planning, development and management of the groundwater resources. Formation of $${\text {CaCO}}_3$$CaCO3 varieties from a carbonated aqueous solution Abstract Experimental studies have been conducted to clarify the paragenetic conditions of ${\text {CaCO}}_3$ varieties, calcite and aragonite formed from the same wall rock. In addition, the solubility dependence of calcite, aragonite, and limestone formed from limestone cave in ${\text {CO}}_2$-saturated solutions was compared with the previous studies. First, the calcite and aragonite were powdered to below 200 meshes. In addition, the powders were, respectively, added into the ${\text {CO}}_2$-saturated distilled water at 8, 13, 18, and $22 \,^\circ {\text {C}}$ and were kept constant for 15 days. The amount of dissolved ${\text {CaCO}}_3$ was then measured. The solubility of aragonite was higher than that of calcite, and the solubility decreased exponentially with increasing temperature. Simultaneous production and growth of calcite and aragonite proceeded only when the saturation of aragonite was reached in aqueous carbonate solution. Conversely, when the dissolved amount of ${\text {CaCO}}_3$ has not been reached, calcite is only formed and grown. In these solutions, aragonite crystals dissolve and calcite crystals grow. The degree of saturation of aragonite can be reached by rapid evaporation of solvent, ${\text {CO}}_2$ gas degassing, and the presence of Mg. However, paragenesis of calcite and aragonite in natural caves can be explained by rapid evaporation of the solvent. A rapid evaporation of the solvent may occur at a place, where a small amount of karst solution flows and a large amount of air flows. In such places, paragenesis of calcite and aragonite is possible. Khuzestan plain continental sabkhas, southwest Iran Abstract Khuzestan Plain is part of the Zagros basin that is located in the southwest of Iran. So far, no comprehensive study has been carried out on these sabkha in Khuzestan plain. This research is the first study on these environments in Khuzestan plain. In this study, continental sabkha of Khuzestan have been divided into four groups: playa, sabkha of dried floodplains, sabkha of dried lagoons, sabkha of ephemeral saline lake (pans). A playa, called Maleh, four sabkha of dried floodplains, with the names of east Zohreh, east Jarrahi, west Jarrahi–east Karoon and west Karoon, two sabkha of dried lagoons, called Hor Al-Azim and Shadegan as well as five sabkha of ephemeral saline lakes were identified in this plain. A total of 87 specimens were collected from the continental sabkha sediments of Khuzestan which classified according Shepard (J Sediment Petrol 24:151–158, 1954). Silt and then clayey silt and sandy silt are the most abundant sediments of continental sabkha of Khuzestan. Origin of crystal dolomite and its reservoir formation mechanism in the Xixiangchi Formation, Upper Cambrian in Southeastern Sichuan basin Abstract This paper takes the thick and widely distributed crystal dolomite of Xixiangchi Formation, Upper Cambrian in Southeastern Sichuan basin as an example, the reservoir characteristics and main controlling factors of crystal dolomite have been analyzed systematically, and the genesis and reservoir formation mechanism of crystal dolomite have been discussed. It shows that the main reservoir rocks of crystal dolomite include powder crystalline dolomite and finely crystalline dolomites, and the intercrystal pores and dissolved intercrystal pores are the main reservoir spaces, with few dissolved vugs and fractures developed in the reservoir. The pore structure analysis shows that the throats of crystal dolomite reservoir are mainly lamellar, reflecting a good configuration between pores and throats, medium- low porosity and low permeability, representing typical porous-type reservoir. Dolomitization analysis indicates that the dolomitization occurred in the penecontemporaneous or early diagenetic stage. The degree of dolomitization decreased gradually from the top to the bottom in each sedimentary cycle, and distribution of dolomite in the study area shows that the content of dolomites decreases from the west to the east, which reflects the degree of dolomitization weakening eastward. Combined with the geochemical research of crystal dolomite, the C and O isotope data reflect the same characteristics of seawater during the late Cambrian. It indicates that the dolomitization might be related to the seepage-reflux of seawater in the early time. Recrystallization played an important role in the genesis of the crystal dolomite, because most of crystal dolomites remain residual granular texture. The intercrystal pores formed by seepage–reflux dolomitization acted as superior seepage channels for the reservoir transformation, and the recrystallization adjusted the previous pores and made them better, while the karstification was the key to the dissolved pore formation. Difference in the relationship between soil CO 2 concentration and the karst-related carbon cycle under different land use types in southwest China Abstract As an important driving force for karstification, soil CO2 has a close relation with karst-related carbon cycle. However, their relationship may be disturbed when H2SO4 and HNO3 participate in karstification. Here, soil CO2 and spring water samples were collected from two catchments to examine the dynamics of carbon under different land use types. The net CO2 consumption at the Baishuwan spring catchment (BSW; range 1.7–2.69 mmol/L, average of 2.21 mmol/L) was higher than it was at the Hougou spring catchment (HG; range − 0.63 to 0.02 mmol/L, average of − 0.24 mmol/L). Due to the participation of H2SO4 and HNO3, CO2 was released from bedrock and reduced net CO2 consumption when this portion of CO2 escaped from the water. With regard to soil CO2 concentration, a bidirectional gradient of CO2 concentration occurred at BSW, while alternating bidirectional and unidirectional gradients occurred at HG. However, the δ13C of soil CO2 could not confirm whether the vertical changes in soil CO2 concentration as well as net CO2 consumption were related to the CO2 released from bedrock to soil. With regard to seasonal changes, net CO2 consumption was consistent with soil CO2 concentration at BSW, while the reverse relationship was found at HG. These observations indicated that soil CO2 concentration was not the dominant factor controlling net CO2 consumption at HG, which was affected by H2SO4 and HNO3, and more CO2 escaped from the water due to the reduced water–rock reaction time in the rainy season. Some carbonate rocks utilized as a building material rocks, Egypt Abstract Studies of the geochemical, mineralogical, petrographical characteristics and the physicochemical properties were carried out on some carbonate rocks, so as to throw light on the possibility of utilizing them as a building stones. The dolomitic and dolostone rocks of Gebel Ataqa and Giran El-Ful quarries have been acquiring potential application in building and industry. Petrographically, the dolomite rocks of the Gebel Ataqa quarries are characterized by dolo-biomicrosparite and dolomitic limestone microfacies for Hassan Alaam quarry and dolosparite microfacies for Arab Contractors quarry, while those of Giran El-Ful (Abu Roash area) are mainly dolo-biomicite microfacies and dolostones. They are deposited in mixing zone environment. Mineralogically, XRD patterns indicate the dolomites of the Ataqa and Giran El-Ful quarries are non-stoichiometric. XRD with DTA revealed that the rocks of the three quarries are consisting mainly of dolomite (Ataqa quarries), calcite and ankarite (Abo Roash quarry), as the main constituents, besides quartz and halite as minor constituents. Geochemically, the normative dolomite contents in the studied rocks with an average ~ 90, ~ 35, and ~ 31% for Arab Contractors, Hassan Alaam and Giran El-Ful quarries; respectively. Thus, the dolomitization was more effective in the Cretaceous carbonates at Arab Contractors quarry than those in the Middle Eocene in Hassan Alaam and Giran El-Ful quarries. Arab Contractors have very high Mg content followed by Hassan Alaam, though impoverished in Na2O, K2O, Al2O3, Fe2O3, SO3, SiO2, TiO2, and Cl. Giran El-Ful quarry has very high Fe2O3 and MgO contents; on the other hand, poor in Na2O, K2O, Al2O3, SO3, SiO2, TiO2, and Cl. Sr contents indicate that the dolomite crystals were deposited in mixing zone environments. The total radioactivity measurements are ranging from 2 to 8 ppm for U and from 3 to 9 ppm for Th. The radioactivity measurements are approximately against to the background level of carbonates, and they are in the permissible limits for carbonates used in cement industries and as building stones. The dolomitic and dolostone rocks of the three quarries are proved chemically suitable for the industries relevant to crushed aggregates and lime production. Physically–mechanically examination revealed that the youngest carbonate deposits in the Middle Eocene (Hassan Alaam quarry) rocks have relatively low porosity, water absorption, and crushability, and highest compressive strength compared with those carbonate rocks of the two other quarries of Upper Cretaceous (Arab Contractors and Giran El-Ful). The petrographical, geochemical, and physical–mechanical observations recommended that the carbonates rocks of Hassan Alaam and Arab Contractors quarries in Gebel Ataqa area clearly can be used in the production of crushed aggregates to utilize in the concrete works. On the other hand, Giran El-Ful quarry can be used only in the mechanical sawing and in the production of limestone blocks.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

08:35

Which search are you on? Adapting to color while searching for shape Abstract Human observers adjust their attentional control settings when searching for a target in the presence of predictable changes in the target-defining feature dimension. We investigated whether observers also adapt to changes in a nondefining target dimension. According to feature integration theory, stimuli that are unique in their environment in a single feature dimension can be detected with little effort. In two experiments, we studied how observers searching for such singletons adapt their attentional control settings to a dynamical change in a nondefining target dimension. Participants searched for a shape singleton and freely chose between two targets in each trial. The two targets differed in color, and the ratio of distractors colored like each target varied dynamically across trials. A model-based analysis with a Bayesian estimation approach showed that participants adapted their target choices to the color ratio: They tended to select the target from the smaller color subset, and switched their preference both when the color ratio changed between gray and heterogeneous colors (Exp. 1) and when it changed between red and blue (Exp. 2). Participants thus tuned their attentional control settings toward color, although the target was defined by shape. We concluded that observers spontaneously adapted their behavior to changing regularities in the environment. Because adaptation was more pronounced when color homogeneity allowed for element grouping, we suggest that observers adapt to regularities that can be registered without attentional resources. They do so even if the changes are not relevant for accomplishing the task—a process presumably based on statistical learning. Configural superiority for varying contrast levels Abstract Observers can search for a target stimulus at a particular speed and accuracy. Adding an identical context to each stimulus can improve performance when the resulting stimuli form clearly discriminable configurations. This search advantage is known as the configural superiority effect (CSE). A recent study showed that embedding these stimuli in noise revealed lower contrast thresholds for part-stimuli compared to configural stimuli (Bratch et al., Journal of Experimental Psychology. Human Perception and Performance, 42(9), 1388–1398, 2016). This contrasts with the accuracy advantages traditionally associated with CSEs. In this study, we aimed to replicate the results of Bratch et al. and asked whether the benefit for part-stimuli held across the full psychometric function. Additionally, we tested whether embedding the stimuli in noise was crucial for obtaining their result and whether different contrast definitions affected the results. Furthermore, we used control stimuli that were more directly comparable. Our results showed a detection benefit for the Gestalt context stimuli in all conditions. Together, these results are in line with the literature on CSEs and do not seem to support the recent claim that Gestalts are processed less efficiently than part stimuli. Inspired by this, we sketch how contrast manipulations could be an additional tool to study how Gestalts are processed. An analysis of the processing of intramodal and intermodal time intervals Abstract In this 3-experiment study, the Weber fractions in the 300-ms and 900-ms duration ranges are obtained with 9 types of empty intervals resulting from the combinations of three types of signals for marking the beginning and end of the signals: auditory (A), visual (V), or tactile (T). There were three types of intramodal intervals (AA, TT, and VV) and 6 types of intermodal intervals (AT, AV, VA, VT, TA, and TV). The second marker is always the same during Experiments 1 (A), 2 (V), and 3 (T). With an uncertainty strategy where the first marker is 1 of 2 sensory signals being presented randomly from trial to trial, the study provides direct comparisons of the perceived length of the different marker-type intervals. The results reveal that the Weber fraction is nearly constant in the three types of intramodal intervals, but is clearly lower at 900 ms than at 300 ms in intermodal conditions. In several cases, the intramodal intervals are perceived as shorter than intermodal intervals, which is interpreted as an effect of the efficiency in detecting the second marker of an intramodal interval. There were no significant differences between the TA and VA intervals (Experiment 1) and between the AV and TV intervals (Experiment 2), but in Experiment 3, the AT intervals were perceived as longer than the VT intervals. The results are interpreted in terms of the generalized form of Weber's law, using the properties of the signals for explaining the additional nontemporal noise observed in the intermodal conditions. Flexible weighting of target features based on distractor context Abstract Models of attention posit that attentional priority is established by summing the saliency and relevancy signals from feature-selective maps. The dimension-weighting account further hypothesizes that information from each feature-selective map is weighted based on expectations of how informative each dimension will be. In the current studies, we investigated the question of whether attentional biases to the features of a conjunction target (color and orientation) differ when one dimension is expected to be more diagnostic of the target. In a series of color-orientation conjunction search tasks, observers saw an exact cue for the upcoming target, while the probability of distractors sharing a target feature in each dimension was manipulated. In one context, distractors were more likely to share the target color, and in another, distractors were more likely to share the target orientation. The results indicated that despite an overall bias toward color, attentional priority to each target feature was flexibly adjusted according to distractor context: RT and accuracy performance was better when the diagnostic feature was expected than unexpected. This occurred both when the distractor context was learned implicitly and explicitly. These results suggest that feature-based enhancement can occur selectively for the dimension expected to be most informative in distinguishing the target from distractors. Visual noise consisting of X-junctions has only a minimal adverse effect on object recognition Abstract In 1968, Guzman showed that the myriad of surfaces composing a highly complex and novel assemblage of volumes can readily be assigned to their appropriate volumes in terms of the constraints offered by the vertices of coterminating edges. Of particular importance was the L-vertex, produced by the cotermination of two contours, which provides strong evidence for the termination of a 2-D surface. An X-junction, formed by the crossing of two contours without a change of direction at the crossing, played no role in the segmentation of a scene. If the potency of noise elements to affect recognition performance reflects their relevancy to the segmentation of scenes, as was suggested by Guzman, gaps in an object's contours bounded by irrelevant X-junctions would be expected to have little or no adverse effect on shape-based object recognition, whereas gaps bounded by L-junctions would be expected to have a strong deleterious effect when they disrupt the smooth continuation of contours. Guzman's roles for the various vertices and junctions have never been put to systematic test with respect to human object recognition. By adding identical noise contours to line drawings of objects that produced either L-vertices or X-junctions, these shape features could be compared with respect to their disruption of object recognition. Guzman's insights that irrelevant L-vertices should be highly disruptive and irrelevant X-vertices would have only a minimal deleterious effect were confirmed. Interacting hands draw attention during scene observation Abstract In this study I examined the role of the hands in scene perception. In Experiment 1, eye movements during free observation of natural scenes were analyzed. Fixations to faces and hands were compared under several conditions, including scenes with and without faces, with and without hands, and without a person. The hands were either resting (e.g., lying on the knees) or interacting with objects (e.g., holding a bottle). Faces held an absolute attentional advantage, regardless of hand presence. Importantly, fixations to interacting hands were faster and more frequent than those to resting hands, suggesting attentional priority to interacting hands. The interacting-hand advantage could not be attributed to perceptual saliency or to the hand-owner (i.e., the depicted person) gaze being directed at the interacting hand. Experiment 2 confirmed the interacting-hand advantage in a visual search paradigm with more controlled stimuli. The present results indicate that the key to understanding the role of attention in person perception is the competitive interaction among objects such as faces, hands, and objects interacting with the person. The space contraction asymmetry in Michotte's launching effect Abstract Previous studies have found that, compared with noncausal events, spatial contraction exists between the causal object and the effect object due to the perceived causality. The present research aims to examine whether the causal object and the effect object have the same effect on spatial contraction. A modified launching effect, in which a bar bridges the spatial gap between the final position of the launcher and the initial position of the target, was adopted. Experiment 1 validates the absolute underestimation of the bar's length between the launcher and the target. Experiment 2a finds that in the direct launching effect, the perceived position of the bar's trailing edge that was contacted by the final launcher was displaced along the objects' direction of movement. Meanwhile, the perceived position of the bar's leading edge that was contacted by the initial target was displaced in opposite direction to the moving direction. The magnitude of the former's displacement was significantly larger than that of the latter, displaying a significant contraction asymmetry. Experiment 2b demonstrates that the contraction asymmetry did not result from the launcher remaining in contact with the edge of the bar. Experiment 3 indicates that contraction asymmetry showed a type of postdictive effect; that is, to some extent, this asymmetry depends on what happens after contact. In conclusion, the space between the causal object and effect object contracts asymmetrically in the launching effect, which implies that the causal object and effect object are perceived as shifting toward each other nonequidistantly in visual space. Dwelling on simple stimuli in visual search Abstract Research and theories on visual search often focus on visual guidance to explain differences in search. Guidance is the tuning of attention to target features and facilitates search because distractors that do not show target features can be more effectively ignored (skipping). As a general rule, the better the guidance is, the more efficient search is. Correspondingly, behavioral experiments often interpreted differences in efficiency as reflecting varying degrees of attentional guidance. But other factors such as the time spent on processing a distractor (dwelling) or multiple visits to the same stimulus in a search display (revisiting) are also involved in determining search efficiency. While there is some research showing that dwelling and revisiting modulate search times in addition to skipping, the corresponding studies used complex naturalistic and category-defined stimuli. The present study tests whether results from prior research can be generalized to more simple stimuli, where target-distractor similarity, a strong factor influencing search performance, can be manipulated in a detailed fashion. Thus, in the present study, simple stimuli with varying degrees of target-distractor similarity were used to deliver conclusive evidence for the contribution of dwelling and revisiting to search performance. The results have theoretical and methodological implications: They imply that visual search models should not treat dwelling and revisiting as constants across varying levels of search efficiency and that behavioral search experiments are equivocal with respect to the responsible processing mechanisms underlying more versus less efficient search. We also suggest that eye-tracking methods may be used to disentangle different search components such as skipping, dwelling, and revisiting. Comparable search efficiency for human and animal targets in the context of natural scenes Abstract In a previous series of studies, we have shown that search for human targets in the context of natural scenes is more efficient than search for mechanical targets. Here we asked whether this search advantage extends to other categories of biological objects. We used videos of natural scenes to directly contrast search efficiency for animal and human targets among biological or nonbiological distractors. In visual search arrays consisting of two, four, six, or eight videos, observers searched for animal targets among machine distractors, and vice versa (Exp. 1). Another group searched for animal targets among human distractors, and vice versa (Exp. 2). We measured search slope as a proxy for search efficiency, and complemented the slope with eye movement measurements (fixation duration on the target, as well as the proportion of first fixations landing on the target). In both experiments, we observed no differences in search slopes or proportions of first fixations between any of the target–distractor category pairs. With respect to fixation durations, we found shorter on-target fixations only for animal targets as compared to machine targets (Exp. 1). In summary, we did not find that the search advantage for human targets over mechanical targets extends to other biological objects. We also found no search advantage for detecting humans as compared to other biological objects. Overall, our pattern of findings suggests that search efficiency in natural scenes, as elsewhere, depends crucially on the specific target–distractor categories. Is it impossible to acquire absolute pitch in adulthood? Abstract Absolute pitch (AP) refers to the rare ability to name the pitch of a tone without external reference. It is widely believed to be only for the selected few with rare genetic makeup and early musical training during the critical period, and therefore acquiring AP in adulthood is impossible. Previous studies have not offered a strong test of the effect of training because of issues like small sample size and insufficient training. In three experiments, adults learned to name pitches in a computerized, gamified and personalized training protocol for 12 to 40 hours, with the number of pitches gradually increased from three to twelve. Across the three experiments, the training covered different octaves, timbre, and training environment (inside or outside laboratory). AP learning showed classic characteristics of perceptual learning, including generalization of learning dependent on the training stimuli, and sustained improvement for at least one to three months. 14% of the participants (6 out of 43) were able to name twelve pitches at 90% or above accuracy, comparable to that of 'AP possessors' as defined in the literature. Overall, AP continues to be learnable in adulthood, which challenges the view that AP development requires both rare genetic predisposition and learning within the critical period. The finding calls for reconsideration of the role of learning in the occurrence of AP, and pushes the field to pinpoint and explain the differences, if any, between the aspects of AP more trainable in adulthood and the aspects of AP that are potentially exclusive for the few exceptional AP possessors observed in the real world.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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It's Not About Ethical Dilemmas: A Survey of Bavarian Veterinary Officers' Opinions on Moral Challenges and an e-Learning Ethics Course Abstract The presented survey focused on moral challenges of Bavarian veterinary officers in their daily work and their expectations of an (e-learning) ethics module in their training program. The results suggest that Bavarian veterinary officers are confronted with morally challenging situations. However, they do not describe these challenges as dilemmas in which the veterinary officers do not know what the moral right choice would be. They are rather convinced to know what they should do from an ethical point of view but see difficulties with the realization as the crucial moral challenge of their profession. The participants in the study do not only expect ethics to help them to find a morally justified way of dealing with moral challenges, but also to gain a better understanding of essential conflicts. In regard to a possible e-learning course on ethics, most veterinary officers were skeptical or highly critical because, from their perspective, ethics needs personal exchange, promoting a dialogue with colleagues, and this is best possible in a classroom-based seminar. Therefore, according to the participants in the survey, if e-learning tools are used, this should only be in combination with classroom-based events. Genome Editing and Responsible Innovation, Can They Be Reconciled? Abstract Genome editing is revolutionising the field of genetics, which includes novel applications to food animals. Responsible research and innovation (RRI) has been advocated as a way of ensuring that a wider-range of stakeholders and publics are able to engage with new and emerging technologies to inform decision making from their perspectives and values. We posit that genome editing is now proceeding at such a fast rate, and in so many different directions, such as to overwhelm attempts to achieving a more reflective pace. An alternative location for reflection is during the much slower process of taking products from the lab to market. We suggest emphasising Responsible Innovation, putting the 'I' back into RRI, and encouraging companies to embrace an RRI approach. We review some previous attempts at developing industry-relevant frameworks for RRI. We then describe two examples of genome editing in livestock; hornless cattle and disease resistant pigs, and reflect on the sorts of questions that could be considered in these two genome editing examples. This paper seeks to take forward the discussion on RRI by extending it to bringing products to market in the context of genome edited livestock. Anthropodicy and the Fate of Humanity in the Anthropocene: From the Disenchantment of Evil to the Re-enchantment of Suffering Abstract The rise of a collective conscience of a new epoch, the Anthropocene, has brought to the fore scientists' predictions of irreversible damage done to the Earth's ecosystems within barely a decade. The passive attitude worldwide of placing the task of overcoming the evil consequences of human activity on specialized forums (e.g., national governments and international organizations) has already proved to be insufficient. In this context, Hamilton seeks to continue Becker's project of laying down the foundations of an "anthropodicy," seen as a humanistic science meant to bring a participatory dimension to the humanity's dealing with the degradation of the conditions of civilized life on Earth. Responsible Innovation for Life: Five Challenges Agriculture Offers for Responsible Innovation in Agriculture and Food, and the Necessity of an Ethics of Innovation Abstract In this special issue we will investigate, from the perspective of agricultural ethics (e.g. animal welfare, agricultural and food ethics, environmental ethics etc.) the potential to develop a Responsible Research and Innovation (RRI) approach to agriculture, and the limitations to such an enterprise. RRI is an emerging field in the European research and innovation (R&I) policy context that aims to balance economic, socio-cultural and environmental aspects in innovation processes. Because technological innovations can contribute significantly to the solution of societal challenges like climate change or food security, but can also have negative societal consequences, it is assumed that social and ethical aspects should be considered during the R&I process. For this reason, the emerging concept of RRI calls for ethical reflection on the nature, scope and applicability of responsibility and innovation in innovation practices in general, and the way social–ethical issues can be applied and addressed in agriculture. The Ethics of Biosurveillance Abstract Governments must keep agricultural systems free of pests that threaten agricultural production and international trade. Biosecurity surveillance already makes use of a wide range of technologies, such as insect traps and lures, geographic information systems, and diagnostic biochemical tests. The rise of cheap and usable surveillance technologies such as remotely piloted aircraft systems (RPAS) presents value conflicts not addressed in international biosurveillance guidelines. The costs of keeping agriculture pest-free include privacy violations and reduced autonomy for farmers. We argue that physical and digital privacy in the age of ubiquitous aerial and ground surveillance is a natural right to allow people to function freely on their land. Surveillance methods must be co-created and justified through using ethically defensible processes such as discourse theory, value-centred design and responsible innovation to forge a cooperative social contract between diverse stakeholders. We propose an ethical framework for biosurveillance activities that balances the collective benefits for food security with individual privacy: (1) establish the boundaries of a biosurveillance social contract; (2) justify surveillance operations for the farmers, researchers, industry, the public and regulators; (3) give decision makers a reasonable measure of control over their personal and agricultural data; and (4) choose surveillance methodologies that give the appropriate information. The benefits of incorporating an ethical framework for responsible biosurveillance innovation include increased participation and accumulated trust over time. Long term trust and cooperation will support food security, producing higher quality data overall and mitigating against anticipated information gaps that may emerge due to disrespecting landholder rights. Agricultural Innovation and the Role of Institutions: Lessons from the Game of Drones Abstract In 2015, observers argued that the fourth agricultural revolution had been initiated. This article focuses on one part of this high-tech revolution: the origin, development, applications, and user value of unmanned aerial systems (UAS). Institutional changes connected to the UAS innovation are analyzed, based on a Swedish case study. The methods included autoethnography. The theoretical frame was composed by four perspectives: innovation, institutions, sustainability, and ethics. UAS can help farmers cut costs and produce higher quantity with better quality, and also has environmental benefits. However, this promising innovation was exposed to institutional forces and suddenly became subordinated the Act of Camera Surveillance. This study illuminates how legislative institutions can inhibit responsible innovation. The study shows that different ethical perspectives can collide with each other. Biblical Gardens in Word Culture: Genesis and History Abstract For nearly 80 years Biblical gardens have been present in the natural and cultural landscape. The first gardens came into existence in the US. The idea to create such gardens spread from the US mainly across Europe, Australia and Israel. These gardens are being made all the time; recently we have observed their dynamic development. This study is to show the effects of the 20 years long scientific work to formulate the original genesis of the Biblical garden idea. The characteristics of 64 facilities situated in 14 countries has been presented for the first time so widely. This enabled us to show both the history of these gardens and how they are situated in the cultural and social context. The effect of various factors inspiring people of various professions to create Biblical gardens both near sacral buildings and within the secular areas has been evidenced. Biblical gardens exercise the principles of gardens of senses and learning gardens. And it is the highly developed semantic layer that makes them stand out. Ethical Concerns in Poultry Production: A German Consumer Survey About Dual Purpose Chickens Abstract The paper offers insights into the acceptability of ethical issues in poultry production and how this situation provides an opportunity to transform the prevailing system into a more sustainable one. The survey among German consumers reveals that killing day-old chicks is a well-known practice and is rated as "very problematic". In contrast, dual-purpose chickens are mostly unknown but are considered a positive alternative to killing day-old chicks (after the concept has been explained). Consumer clusters were identified regarding purchasing criteria for dual-purpose chickens, purchasing routines and socio-economic factors. Three of the five clusters—the perfectionists, idealists, and realists—turned out to be potential buyers. To develop a suitable marketing strategy, it is recommended that the added value of dual-purpose chickens be comprehensibly communicated. From a multi-level perspective, rearing dual-purpose chickens has a competitive disadvantage compared to system-compliant alternatives (in-ovo sexing, "lay hen brothers"). Through increasing external pressure, the different alternatives can jointly contribute to a regime shift. Entanglements of Water Management Abstract This review essay investigates Andrea Ballestero's A Future History of Water (Duke University Press, Durham, 2019), Jeremy Schmidt's Water: Abundance, Scarcity, and Security in the Age of Humanity (New York University Press, New York, 2017), and Wade Graham's Braided Waters: Environment and Society in Molokai, Hawai'i (University of California, Oakland, 2018) within the wider theme of water-human relationships. More specifically, these books provide insight into the human dimensions of water management as they explore the process of how water impacts and drives economic, social, and political change. By doing this, Ballestero, Schmidt, and Graham highlight water's agency and the vital role it plays in a variety of locations and situations. Broadly speaking, works like these help move water beyond discussions limited to ecological science, giving this resource a starring role in crucial discussions ranging from policy and economics to community development and social equity. In this regard, environmental issues are holistic matters that must engage cultural, economic, political, and religious dimensions as well as ecological issues. Collectively these books show that water's fluctuating nature dictates the structure of our world, permeating every issue from the daily to the global while reinforcing the need to look critically at this life-giving resource. Managing Socio-Ethical Challenges in the Development of Smart Farming: From a Fragmented to a Comprehensive Approach for Responsible Research and Innovation Abstract Smart farming (also referred to as digital farming, digital agriculture and precision agriculture) has largely been driven by productivity and efficiency aims, but there is an increasing awareness of potential socio-ethical challenges. The responsible research and innovation (RRI) approach aims to address such challenges but has had limited application in smart farming contexts. Using smart dairying research and development (R&D) in New Zealand (NZ) as a case study, we examine the extent to which principles of RRI have been applied in NZ smart dairying development and assess the broader lessons for RRI application in smart farming. We draw on insights from: a review of research on dairy technology use in NZ; interviews with smart dairying stakeholders; and the application of an analytical framework based on RRI dimensions. We conclude that smart dairying R&D and innovation activities have focused on technology development and on-farm use without considering socio-ethical implications and have excluded certain actors such as citizens and consumers. This indicates that readiness to enact RRI in this context is not yet optimal, and future RRI efforts require leadership by government or dairy sector organisations to fully embed RRI principles in the guidelines for large R&D project design (what has also been referred to as 'RRI maturity'). More broadly, enacting RRI in smart farming requires initial identification of RRI readiness in a given sector or country and devising a roadmap and coherent project portfolio to support capacity building for enacting RRI. Additionally, methods (such as RRI indicators) for operationalising RRI must be adapted to the context of the national or sectoral innovation system in which smart farming is being developed.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

08:33

Quantitative Assessment of Elagolix Enzyme-Transporter Interplay and Drug–Drug Interactions Using Physiologically Based Pharmacokinetic Modeling AbstractIntroduction Elagolix is approved for the management of moderate-to-severe pain associated with endometriosis. The aim of this analysis was to develop a physiologically based pharmacokinetic (PBPK) model that describes the enzyme-transporter interplay involved in the disposition of elagolix and to predict the magnitude of drug–drug interaction (DDI) potential of elagolix as an inhibitor of P-glycoprotein (P-gp) and inducer of cytochrome P450 (CYP) 3A4.Methods A PBPK model (SimCYP® version 15.0.86.0) was developed using elagolix data from in vitro, clinical PK and DDI studies. Data from DDI studies were used to quantify contributions of the uptake transporter organic anion transporting polypeptide (OATP) 1B1 and CYP3A4 in the disposition of elagolix, and to quantitatively assess the perpetrator potential of elagolix as a CYP3A4 inducer and P-gp inhibitor.Results After accounting for the interplay between elagolix metabolism by CYP3A4 and uptake by OATP1B1, the model-predicted PK parameters of elagolix along with the DDI AUC∞ and Cmax ratios, were within 1.5-fold of the observed data. Based on model simulations, elagolix 200 mg administered twice daily is a moderate inducer of CYP3A4 (approximately 56% reduction in midazolam AUC∞). Simulations of elagolix 150 mg administered once daily with digoxin predicted an increase in digoxin Cmax and AUC∞ by 68% and 19%, respectively.Conclusions A PBPK model of elagolix was developed, verified, and applied to characterize the disposition interplay between CYP3A4 and OATP1B1, and to predict the DDI potential of elagolix as a perpetrator under dosing conditions that were not tested clinically. PBPK model-based predictions were used to support labeling language for DDI recommendations of elagolix. Acknowledgement to Referees Fetal Physiologically Based Pharmacokinetic Models: Systems Information on Fetal Blood Components and Binding Proteins AbstractBackground Fetal blood and plasma volume and binding components are critical parameters in a fetal physiologically based pharmacokinetic model. To date, a comprehensive review of their changes during fetal development has not been reported.Objective The objective of this work was to collate and analyze physiological information on fetal blood and plasma volume and binding component data during development and to provide a mathematical description of these parameters that can be integrated within a fetal physiologically based pharmacokinetic model.Methods A comprehensive literature search was conducted on fetal blood and plasma volume and binding component parameters and their changes during growth from apparently healthy fetuses from uncomplicated pregnancies. Collated data were assessed, integrated, and analyzed to establish continuous mathematical functions describing their growth trends with fetal age and weight.Results Data were available from 14 studies for blood, ten studies for hematocrit, 12 studies for albumin, and four studies for alpha-1-acid glycoprotein, while plasma and red blood cell volumes were described based on blood and hematocrit data. Fetal physiologically based pharmacokinetic parameters, including blood, plasma and red blood cell volumes, hematocrit, serum albumin, and acid glycoprotein were quantified as a function of fetal age and weight. Variability around the mean parameters at different fetal ages was also investigated. The growth of each of these parameters was different (with respect to direction and monotonicity).Conclusions Despite the limitations identified in the availability of some values, the collected data presented in this article provide a useful resource for fetal physiologically based pharmacokinetic modeling. Potential applications include predicting xenobiotic exposure and risk assessment in the fetus following maternally administered drugs or unintended exposure to environmental toxicants. Setting the Dose of Checkpoint Inhibitors: The Role of Clinical Pharmacology Abstract Cancer immunotherapy is based on checkpoint inhibitors (CPIs) that significantly improve the clinical outcome of several malignant diseases. These inhibitors are monoclonal antibodies (mAbs) directed at cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), or programmed death-ligand 1 (PD-L1), sharing most of the clinical pharmacokinetic characteristics of mAb targeted therapies, all of which differ from those of cytotoxics and small molecules. Establishing the labeled dose of mAbs, and particularly of the CPIs, represents a true challenge. This review therefore examines the main criteria used for dose selection, along with their limits. The relationships between CPI pharmacokinetic parameters and treatment outcome (efficacy and/or toxicity) differ somewhat among the various drugs, but general features can be identified. Nevertheless, the interpretation of these relationships remains quite controversial. A first interpretation asserts that inter-individual pharmacokinetic variability in clearance has an impact on outcome and should be taken into consideration for dosing individualization. The second considers that higher clearance values observed in some patients result from characteristics associated with poor predictive factors of efficacy. Finally, the schedule, and particularly its frequency of administration, merits rethinking. Correction to: Evidence-Based Design of Fixed-Dose Combinations: Principles and Application to Pediatric Anti-Tuberculosis Therapy In the online supplementary Population Pharmacokinetics of Blinatumomab in Pediatric and Adult Patients with Hematological Malignancies AbstractBackground and objectives Blinatumomab (BLINCYTO®) is a novel bispecific T cell engager (BiTE®) approved in the USA for the treatment of relapsed or refractory B cell precursor acute lymphoblastic leukemia (ALL) in children and adults, as well as minimal residual disease ALL in adults. This analysis characterized the population pharmacokinetics of intravenous blinatumomab in pediatric and adult patients.Methods A total of 2417 serum concentrations of blinatumomab from 674 patients, including adult (n = 628) and pediatric patients (n = 46), from eight clinical studies were analyzed. The impact of covariates on pharmacokinetic parameters were explored, and significant covariates were further evaluated using a simulation approach.Results Blinatumomab pharmacokinetics were described by a one-compartment linear model with first-order elimination, a clearance (CL) of 2.22 L/h, and a central volume of 5.98 L. A statistically significant effect of body surface area (BSA) on CL was observed. The smallest BSA of 0.37 m2 in the pediatric population was associated with a 63% reduction in blinatumomab systemic CL, relative to an adult patient with the median BSA (1.88 m2), supporting the use of BSA-based dosing in patients of lower bodyweight. The BSA effect was minimal, with a ≤ 25% change in CL over the range of BSA in adults, supporting no need for BSA-based dosing.Conclusions Blinatumomab pharmacokinetics were adequately described by a one-compartment linear model with first-order elimination. No covariates other than BSA on CL were identified as significant. BSA-based dosing should be considered for lightweight patients to minimize inter-subject variability in blinatumomab exposure. Clinical Pharmacokinetics and Pharmacodynamics of Etravirine: An Updated Review Abstract Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of human immunodeficiency virus type 1 infection. It is a potent inhibitor of HIV reverse transcriptase and retains activity against wild-type and most NNRTI-resistant HIV. The pharmacokinetic profile of etravirine and clinical data support twice-daily dosing, although once-daily dosing has been investigated in treatment-naïve and treatment-experienced persons. Despite similar pharmacokinetic and pharmacodynamic results compared with twice-daily dosing, larger studies are needed to fully support once-daily etravirine dosing in treatment-naïve individuals. Etravirine is reserved for use in third- or fourth-line antiretroviral treatment regimens, as recommended, for example, in treatment guidelines by the US Department of Health and Human Services—Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Etravirine exhibits the potential for bi-directional drug–drug interactions with other antiretrovirals and concomitant medications through its interactions with cytochrome P450 (CYP) isozymes: CYP3A4, CYP2C9, and CYP2C19. This review summarizes the pharmacokinetic and pharmacodynamic parameters of etravirine, with particular attention to information on drug–drug interactions and use in special patient populations, including children/adolescents, women, persons with organ dysfunction, and during pregnancy. Population Pharmacokinetics of Mycophenolic Acid Co-Administered with Tacrolimus in Corticosteroid-Free Adult Kidney Transplant Patients AbstractBackground and Objective Mycophenolic acid is commonly prescribed to adult kidney transplant recipients. Mycophenolic acid is extensively metabolized to mycophenolic acid-glucuronide (major metabolite) and mycophenolic acid-acyl-glucuronide (minor metabolite). We hypothesized that (1) adult kidney transplant patients on corticosteroid-free regimens exhibit unique mycophenolic acid population pharmacokinetics compared with patients receiving corticosteroid-based therapy, and (2) mycophenolic acid clearance is directly dependent on glucuronide metabolite formation.Methods Non-linear mixed-effects modeling was conducted with MonolixSuite-2018R1 (n = 27). Optimal pharmacokinetic models were selected based on objective function values, standard errors, and biological plausibility.Results Clinical demographic data were sex (female, 16), age (47 ± 13 years, mean ± standard deviation), weight (70 ± 16 kg), height (165 ± 9 cm), albumin (43 ± 4 g/L), serum creatinine (102 ± 27 µmol/L), estimated glomerular filtration rate (61 ± 16 mL/min/1.73 m2), mycophenolic acid dosage (1.4 ± 0.5 g/day, as mycophenolate mofetil), and tacrolimus dosage (5 ± 3 mg/day, immediate release). The population pharmacokinetics of mycophenolic acid can be described by a two-compartment first-order absorption with lag time, and a linear elimination structural model. The apparent oral clearance estimate in the final model (population mean, relative standard error) was 2.87 L/h, 42.3%, which is lower than that reported for similar patients on corticosteroid-based regimens (11.9–26.3 L/h). Other pharmacokinetic parameters were comparable to historical data obtained in corticosteroid-based patients. Both mycophenolic acid-acyl-glucuronide trough concentration and the area under the concentration–time curve ratio were significant covariates that reduced mycophenolic acid apparent oral clearance from 16.5 (base model) to 2.87 L/h. The model was evaluated based on bootstrapping, visual predictive checks, and diagnostic plots.Conclusions Our novel findings suggest the potential need to reduce mycophenolic acid dosage in subjects on corticosteroid-free regimens. Corticosteroid-free subjects may also be more sensitive to drug/gene interactions. Requirements to Establishing Confidence in Physiologically Based Pharmacokinetic (PBPK) Models and Overcoming Some of the Challenges to Meeting Them Abstract When scientifically well-founded, the mechanistic basis of physiologically based pharmacokinetic (PBPK) models can help reduce the uncertainty and increase confidence in extrapolations outside the studied scenarios or studied populations. However, it is not always possible to establish mechanistically credible PBPK models. Requirements to establishing confidence in PBPK models, and challenges to meeting these requirements, are presented in this article. Parameter non-identifiability is the most challenging among the barriers to establishing confidence in PBPK models. Using case examples of small molecule drugs, this article examines the use of hypothesis testing to overcome parameter non-identifiability issues, with the objective of enhancing confidence in the mechanistic basis of PBPK models and thereby improving the quality of predictions that are meant for internal decisions and regulatory submissions. When the mechanistic basis of a PBPK model cannot be established, we propose the use of simpler models or evidence-based approaches. Phenotyping of Human CYP450 Enzymes by Endobiotics: Current Knowledge and Methodological Approaches Abstract Drug response is subject to an important within- and between-individual variability owing, mainly, to pharmacokinetic and pharmacodynamic factors. Pharmacokinetics includes metabolism by cytochrome P450 (CYP450), major enzymes of phase I reactions that are responsible for the biotransformation of around 60% of the currently approved drugs. CYP450 activity and/or expression are influenced by multiple intrinsic and extrinsic factors, such as drug–drug interactions or genetic polymorphisms. Present phenotyping strategies with xenobiotics used to assess CYP450 activity could be replaced by less invasive procedures using endogenous CYP450 biomarkers. In this work, we review existing knowledge on endobiotics and their ability to characterise variability of the CYP1A2, CYP2C19, CYP2D6 and CYP3A enzymes in humans. To date, it appears that there is a lack of clinical data for the majority of the endogenous compounds described in the literature or some important limitations to allow their use in clinical practice. Additional studies are needed to fill the gap or to identify new candidates, in particular through the use of metabolomics. The use of multivariate models is also a very promising approach to enhance prediction by combining several endogenous phenotyping metrics and other covariates.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

08:33

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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All Hands On Deck: Evolving Best Practices for Optimal Intraoperative Hand Hygiene No abstract available Hocus, PoCUS: OSA Diagnosis? No abstract available Descriptive Statistics in Medical Research No abstract available Hand Hygiene and Relearning Lessons From the Past No abstract available Untapped Potential of Dexmedetomidine No abstract available Perioperative Screening for Sleep Apnea: The New Frontier of Point-of-Care Ultrasound No abstract available Methadone: New Indications for an Old Drug? No abstract available Tranexamic Acid for Acute Hemorrhage: When Is Enough Evidence Enough? No abstract available Guidelines, Practice Parameters, and Consensus Statements in Anesthesiology No abstract available Methylprednisolone Does Not Reduce Acute Postoperative Pain After Cardiac Surgery: Subanalysis of a Randomized Clinical Trial BACKGROUND: Pain after cardiac surgery is largely treated with opioids, but their poor safety profile makes nonopioid medications attractive as part of multimodal pathways. Anti-inflammatory drugs reduce acute postoperative pain, but the role of steroids in reducing acute poststernotomy pain is unclear. We evaluated the association between the intraoperative administration of methylprednisolone and postoperative analgesia, defined as a composite of pain scores and opioid consumption, during the initial 24 hours after cardiac surgery. METHODS: We conducted a post hoc retrospective analysis of a large clinical trial in which adults having cardiac surgery were randomized 1:1 to receive 2 intraoperative doses of 250 mg IV methylprednisolone or placebo. Pain scores and opioid consumption were collected during the initial 24 hours after surgery. Methylprednisolone was considered to be associated with better pain control than placebo if proven noninferior (not worse) on both pain scores (defined a priori with delta of 1 point) and opioid consumption (delta of 20%) and superior to placebo in at least 1 of the 2 outcomes. This test was repeated in the opposite direction (testing whether placebo is better than methylprednisolone on postoperative pain management). RESULTS: Of 251 eligible patients, 127 received methylprednisolone and 124 received placebo. Methylprednisolone was noninferior to placebo on pain with difference in mean (CI) pain scores of −0.25 (−0.71 to 0.21); P < .001. However, methylprednisolone was not noninferior to placebo on opioid consumption (ratio of geometric means [CI]: 1.11 [0.64–1.91]; P = .37). Because methylprednisolone was not noninferior to placebo on both outcomes, we did not proceed to superiority testing based on the a priori stopping rules. Similar results were found when testing the opposite direction. CONCLUSIONS: In this post hoc analysis, we could not identify a beneficial analgesic effect after cardiac surgery associated with methylprednisolone administration. There are currently no data to suggest that methylprednisolone has significant analgesic benefit in adults having cardiac surgery.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

08:32

Refractory dependence on opioid analgesics No abstract available Itch sensitization? A systematic review of studies using quantitative sensory testing in patients with chronic itch As well established for patients with chronic pain, patients suffering from chronic itch also exhibit signs of peripheral and central sensitization. This has been linked to parallel neuroplastic sensitization processes. However, for chronic itch, sensitization has not yet been systematically assessed, studied, and hence validated. This review (Prospero CRD42016043002) summarizes and meta-analytically evaluates whether sensory aberrations including sensitization for itch occur in chronic itch. Databases PubMed, Embase, and Cochrane Library were searched for studies investigating somatosensory sensitivity assessment by quantitative sensory testing stimuli, including experimental cutaneous chemical pruritic provocations, in patients with chronic itch from skin/neurological conditions and compared with healthy controls. Outcomes were extracted for lesional and nonlesional skin, and risk of biases were assessed. Meta-analyses were performed when sufficient quantitative data were available. Of 4667 identified articles, 46 were included and 25 were eligible for meta-analyses. Patients (66% atopic dermatitis [AD]) were found more sensitive than the controls to histamine-evoked itch in lesional skin (standardized mean difference [SMD]: 0.66 confidence interval [CI]: 0.16-1.15), but not nonlesionally (SMD: −0.26 [CI: −0.58 to 0.06]). Cowhage did not evoke more itch in nonlesional skin of patients as compared to the controls (SMD: 0.38 [CI: −0.04 to 0.81]). For numerous other chemical provocations as well as for mechanical, thermal, and electrical stimulation paradigms, results were ambiguous or based on few studies. Patients with chronic itch are only robustly sensitized to various chemical pruritic stimuli when applied lesionally. More studies on somatosensory aberrations in chronic itch conditions other than AD are needed to establish whether sensitization is robustly present across chronic itch conditions. Conditioned pain modulation as a biomarker of chronic pain: a systematic review of its concurrent validity Conditioned pain modulation (CPM) is a promising psychophysical biomarker of central pain mechanisms because it significantly discriminates patients with chronic pain from healthy controls. Nevertheless, it is unclear in what extent CPM assessed experimentally is correlated with clinical manifestations of pain. To assess the concurrent validity of CPM, we performed a systematic review of the literature reporting correlations between CPM responses and pain intensity, disability, duration, and area in patients with different chronic pain conditions. We included 32 studies that altogether encompassed data from 1958 patients and provided 62 correlations. The majority of the results (69%) reported nonsignificant correlations between CPM efficiency and clinical manifestations of pain, whereas the remaining results showed a correlation between CPM reduction and worse clinical symptoms of pain. The modality of stimulation, the type of pain, and the stimulation site appear to be critical variables that influenced the pattern of results. Given that most of the studies were conducted with highly heterogeneous methodologies and unclear risk of bias, the findings highlight the need for future studies using standardized measures of clinical and experimental pain before considering CPM as a valid biomarker of pain. We discuss some guidelines to overcome the constraints in this promising line of research. A randomized pilot study to investigate the effect of opioids on immunomarkers using gene expression profiling during surgery Endogenous opioid peptides and exogenous opioids modulate immune function, and animal and human studies have shown that some have a depressant immunomodulatory effect. This is potentially of high clinical significance, eg, in cancer patients and surgery. The primary objective of this pilot study was to evaluate the effect of morphine and oxycodone on immune pathways associated with immunosuppression in gynecological laparotomy patients. Gene expression was analyzed in CD4+, CD8+, and natural killer (NK) cells using the 3′ Affymetrix microarray. Patients were randomized to receive morphine, oxycodone, or nonopioid "control" analgesia during and after surgery. Genes demonstrating differential expression were those with a ≥±2-fold difference and P-value ≤0.05 after analysis of variance. Cytometric bead array and NK cell degranulation assay were used to investigate changes in serum cytokine concentration and in NK cell cytotoxicity, respectively. Forty patients had satisfactory RNA which was hybridized to gene chips. Genes were identified (Partek Genomics Suite 6.6) at baseline, 2, 6, and 24 hours and were either ≥2-fold upregulated or downregulated from baseline. At 2 hours, a large number of genes were downregulated with morphine but not with control analgesia or oxycodone. Statistically significant increases in IL-6 concentrations were induced by morphine only; NK cell activity was suppressed with morphine, but maintained with oxycodone and epidural analgesia. Gene expression profiles suggest that at 2 hours, post incision morphine appeared to be immunosuppressive as compared to oxycodone and nonopioid control analgesia. Epidermal expression of human TRPM8, but not of TRPA1 ion channels, is associated with sensory responses to local skin cooling Human cold perception and nociception play an important role in persisting pain. However, species differences in the target temperature of thermosensitive ion channels expressed in peripheral nerve endings have fueled discussions about the mechanism of cold nociception in humans. Most frequently implicated thermosensors are members of the transient receptor potential (TRP) ion channel family TRPM8 and TRPA1. Regularly observed, distinct cold pain phenotype groups suggested the existence of interindividually differing molecular bases. In 28 subjects displaying either high or medium sensitivity to local cooling of the skin, the density at epidermal nerve fibers of TRPM8, but not that of TRPA1 expression, correlated significantly with the cold pain threshold. Moreover, reproducible grouping of the subjects, based on high or medium sensitivity to cooling, was reflected in an analogous grouping based on high or low TRPM8 expression at epidermal nerve fibers. The distribution of TRPM8 expression in epidermal nerve fibers provided an explanation for the previously observed (bi)modal distribution of human cold pain thresholds which was reproduced in this study. In the light of current controversies on the role of human TRPA1 ion channels in cold pain perception, the present observations demonstrating a lack of association of TRPA1 channel expression with cold sensitivity–related measures reinforce doubts about involvement of this channel in cold pain in humans. Since TRP inhibitors targeting TRPM8 and TRPA1 are currently entering clinical phases of drug development, the existence of known species differences, in particular in the function of TRPA1, emphasizes the increasing importance of new methods to directly approach the roles of TRPs in humans. Dermorphin [D-Arg2, Lys4] (1-4) amide inhibits below-level heat hypersensitivity in mice after contusive thoracic spinal cord injury Opioid use for chronic pain is limited by severe central adverse effects. We examined whether activating mu-opioid receptors (MORs) in the peripheral nervous system attenuates spinal cord injury (SCI) pain-like behavior in mice. We produced a contusive SCI at the T10 vertebral level and examined motor and sensory dysfunction for 6 weeks. At 6 weeks, we tested the effect of subcutaneous (s.c.) injection of dermorphin [D-Arg2, Lys4] (1-4) amide (DALDA), a peripherally acting MOR-preferring agonist, on mechanical and heat hypersensitivity. Basso mouse scale score was significantly decreased after SCI, and mice showed hypersensitivity to mechanical and heat stimulation at the hind paw beginning at 2 weeks, as indicated by increased paw withdrawal frequency to mechanical stimulation and decreased paw withdrawal latency to heat stimulation. In wild-type SCI mice, DALDA (1 mg/kg, s.c.) attenuated heat but not mechanical hypersensitivity. The effect was blocked by pretreatment with an intraperitoneal injection of methylnaltrexone (5 mg/kg), a peripherally restricted opioid receptor antagonist, and was also diminished in Pirt-MOR conditional knockout mice. DALDA did not adversely affect exploratory activity or induced preference to drug treatment in SCI mice. In vivo calcium imaging showed that DALDA (1, 10 mg/kg, s.c.) inhibited responses of small dorsal root ganglion neurons to noxious heat stimulation in Pirt-GCaMP6s mice after SCI. Western blot analysis showed upregulation of MOR in the lumbar spinal cord and sciatic nerves at 6 weeks after SCI. Our findings suggest that peripherally acting MOR agonist may inhibit heat hypersensitivity below the injury level with minimal adverse effects. Fatty acid suppression of glial activation prevents central neuropathic pain after spinal cord injury About half of patients with spinal cord injury (SCI) develop debilitating central neuropathic pain (CNP), with no effective treatments. Thus, effective, safe, and novel therapies are needed urgently. Previously, docosahexaenoic acid (DHA) was reported to confer neuroprotection in preclinical SCI models. However, its therapeutic potential on SCI-CNP remains to be elucidated. Here, we demonstrated for the first time that intravenous DHA administrations with 3-day intervals (250 nmol/kg; starting 30 minutes after injury and maintained for 6 weeks) effectively prevented SCI-CNP development in a clinically relevant rat contusion model. SCI-CNP was assessed by a novel sensory profiling approach combining evoked pain measures and pain-related ethologically relevant rodent behaviours (burrowing, thigmotaxis, and place/escape avoidance) to mimic those for measuring human (sensory, affective, cognitive, and spontaneous) pain. Strikingly, already established SCI-CNP could be abolished partially by similar DHA administrations, starting from the beginning of week 4 after injury and maintained for 4 weeks. At spinal (epicenter and L5 dorsal horns) and supraspinal (anterior cingulate cortex) levels, both treatment regimens potently suppressed microglial and astrocyte activation, which underpins SCI-CNP pathogenesis. Spinal microgliosis, a known hallmark associated with neuropathic pain behaviours, was reduced by DHA treatments. Finally, we revealed novel potential roles of peroxisome proliferator–activated and retinoid X receptors and docosahexaenoyl ethanolamide (DHA's metabolite) in mediating DHA's effects on microglial activation. Our findings, coupled with the excellent long-term clinical safety of DHA even in surgical and critically ill patients, suggest that systemic DHA treatment is a translatable, effective, safe, and novel approach for preventing and managing SCI-CNP. Motor simulation is disturbed when experiencing pain While the contribution of social processes to pain perception is well documented, surprisingly little is known about the influence of pain on social perception. In particular, an important question is how pain modulates the processing of other people's actions. To address this question, the current study tests, using automatic imitation, the hypothesis that pain interferes with motor simulation—that is, the processing of observed actions in the motor system. Participants in both experiments performed an automatic imitation task requiring them to abduct their index or little finger while they saw someone else performing either a congruent or incongruent action. Automatic imitation was measured in a pain-free context, a context where pain was coupled to the execution of a movement (experiment 1), and a context where pain occurred randomly (experiment 2). The results revealed that automatic imitation, indexed by slower responses on incongruent compared with congruent trials, was reduced when experiencing pain, both when pain was linked to movement execution and when it was not. Thus, the current study shows that pain leads to reduced motor processing of others' behavior and, as such, has important implications for understanding the social difficulties associated with pain. Brain dysfunction in chronic pain patients assessed by resting-state electroencephalography Chronic pain is a common and severely disabling disease whose treatment is often unsatisfactory. Insights into the brain mechanisms of chronic pain promise to advance the understanding of the underlying pathophysiology and might help to develop disease markers and novel treatments. Here, we systematically exploited the potential of electroencephalography to determine abnormalities of brain function during the resting state in chronic pain. To this end, we performed state-of-the-art analyses of oscillatory brain activity, brain connectivity, and brain networks in 101 patients of either sex suffering from chronic pain. The results show that global and local measures of brain activity did not differ between chronic pain patients and a healthy control group. However, we observed significantly increased connectivity at theta (4-8 Hz) and gamma (>60 Hz) frequencies in frontal brain areas as well as global network reorganization at gamma frequencies in chronic pain patients. Furthermore, a machine learning algorithm could differentiate between patients and healthy controls with an above-chance accuracy of 57%, mostly based on frontal connectivity. These results suggest that increased theta and gamma synchrony in frontal brain areas are involved in the pathophysiology of chronic pain. Although substantial challenges concerning the reproducibility of the findings and the accuracy, specificity, and validity of potential electroencephalography-based disease markers remain to be overcome, our study indicates that abnormal frontal synchrony at theta and gamma frequencies might be promising targets for noninvasive brain stimulation and/or neurofeedback approaches. Heme and sensory neuropathy: insights from novel mutations in the heme exporter feline leukemia virus subgroup C receptor 1 Hereditary sensory and autonomic neuropathies (HSANs) are a group of clinically and genetically heterogeneous disorders of the peripheral nervous system mainly characterized by impaired nociception and autonomic dysfunction. We previously identified heme metabolism as a novel pathway contributing to sensory neurons maintenance and nociception. Indeed, we reported mutations in the feline leukemia virus subgroup C receptor 1 (FLVCR1) gene in individuals affected by HSAN. FLVCR1 gene encodes for 2 heme export proteins, FLVCR1a (plasma membrane) and FLVCR1b (mitochondria), crucially involved in the regulation of cellular heme homeostasis. Here, we report on 2 additional patients carrying novel biallelic mutations in FLVCR1 translation initiation codon (c.2T>C; p.(Met1Thr) and c.3G>T; p.(Met1Ile)). We overexpressed the c.2T>C; p.(Met1Thr) mutant in human cell lines and we describe its impact on protein structure and function in comparison with other HSAN-related mutations. We found that the mutation interferes with translation in 2 different ways: by lowering levels of translation of wild-type protein and by inducing translation initiation from a downstream in-frame ATG, leading to the production of an N-terminal truncated protein that is retained in the endoplasmic reticulum. The impact of different kinds of mutations on FLVCR1a localization and structure was also described. The identification of novel FLVCR1 mutations in HSAN reinforces the crucial role of heme in sensory neuron maintenance and pain perception. Moreover, our in vitro findings demonstrate that heme export is not completely lost in HSAN patients, thus suggesting the possibility to improve FLVCR1 expression/activity for therapeutic purposes.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

08:32

Substance Use Disorders Among Industry Workers in Egypt Background and Objective: Substance abuse in the workplace is a major public health problem. The objectives of this study are to: (1) to determine the prevalence and associated risk factors of substance abuse, drug-related problems, and drug dependence among industrial workers; (2) to identify patients' views of the pros and cons of their drug use and their treatment readiness; and (3) to assess the severity of substance abuse according to the Addiction Severity Index (ASI) scale in substance users. Subjects and Methods: A total of 353 industrial workers from 5 factories in 10th of Ramadan city in Egypt were included in the study. The participants were interviewed to collect sociodemographic and clinical data using the Structural Clinical Interview for DSM-IV-Axis I (SCID-I), the Drug Use Disorder Identification Test (DUDIT), DUDIT-Extended version and the Addiction Severity Index (ASI). The participants were screened for drug abuse by urine analysis. Results: The prevalence rates of smoking and substance abuse were 27.6% and 18.3%, respectively. The most commonly abused drugs were tramadol (66.2%), cannabis (55.4%), and alcohol (38.5%). Compared with controls, smokers and substance users were more likely to be males and were older. Smokers were 7 times more likely to use substances. Substance dependence was associated with a younger age of substance use onset and alcohol abuse. Conclusions: Smoking and substance abuse are common among industrial workers. Tramadol and cannabis are the most commonly abused substances. Smoking, older age, and male sex are correlates of substance abuse. Alcohol abuse is associated with dependence. Familial Opioid Misuse and Family Cohesion: Impact on Family Communication and Well-being Objectives: This study aimed to understand family communication and overall well-being of young adults in the context of familial opioid misuse using the family systems framework. Methods: A cross-sectional, mixed-methods, online survey of young adults aged 18 to 30 years (n=137) was conducted. A cluster analysis was performed based on family organization and structural characteristics. MANCOVA was utilized to compare groups identified using the cluster analysis in terms of (1) family's belief about opioid misuse, (2) worry regarding opioid misuse, (3) family communication, and (4) overall well-being of young adults. Results: A cluster analysis resulted in three groups (group 1: no familial opioid misuse with high family cohesion; group 2: familial opioid misuse with moderate family cohesion; group 3: those with/without familial opioid misuse and low family cohesion). Group 3 had the lowest family communication compared to group 1 and group 2 (P<0.001 and P=0.001, respectively) and had lower overall well-being compared to group 1 (P=0.008). Group 2 had a higher worry score than group 1 (P<0.001). Qualitative analysis using Labov's narrative analysis elucidated that having someone misusing opioids with other substances (eg, alcohol) in the family can negatively impact the emotions of family members. Conclusions: Our findings indicated that family cohesion had a greater impact on family communication and overall well-being of young adults even in the presence of familial opioid misuse. This suggests that higher family cohesion may positively influence young adults to cope with issues related to familial opioid misuse. Pregabalin Does Not Reduce Opioid Withdrawal Symptoms: A Randomized Controlled Trial Background and Aim: Controlling the symptoms of opioid withdrawal syndrome is important for the treatment of opioid addiction. There is very limited evidence on the effectiveness of pregabalin on opioid withdrawal syndrome. The present study examines the effectiveness of pregabalin in reducing opioid withdrawal symptoms. Methods: This double-blind clinical-trial was conducted on noninjecting opioid users diagnosed with opioid dependence and referred to the Addiction Treatment Center of Khorshid Hospital in Isfahan, Iran, in 2015 and 2016. The patients were divided into intervention and control groups, and both groups received Buprenorphine for the routine management of opioid withdrawal syndrome. The intervention group additionally received 450 mg/d of pregabalin while the control group received placebos. Opioid withdrawal symptoms were evaluated using the Short Opioid Withdrawal Scale (SOWS). Data were analyzed in SPSS-20. Descriptive data were reported as mean±SD. The analytic data were analyzed using the repeated-measures ANOVA. The level of statistical significance was set at P-value<0.05. Results: The mean age was 41.58±10.09 in the intervention group and 44±8.87 years in the control group (P=0.47). None of the assessed signs and symptoms differed significantly between the 2 groups. Conclusions: The results did not show the superiority of the 450-mg/day pregabalin regimen versus the placebo for controlling the symptoms of opioid withdrawal syndrome. Further studies administering higher doses of pregabalin are recommended. The Effects of Repetitive Transcranial Magnetic Stimulation in Reducing Cocaine Craving and Use Given the scale and complexity of cocaine abuse in individual, social and public health terms, new forms of treatment are urgently needed. The therapeutic uses of Transcranial Magnetic Stimulation (TMS) for reducing consumption by those who abuse cocaine have been explored since 2003. This article reports an integrative review of seven trials carried out from 2007 to 2016, investigating the use of TMS on subjects abusing cocaine. The analysis was categorized into 5 different topics (1) area of intervention; (2) hemisphere; (3) number of pulses and intensity; (4) safety and adverse effects; and (5) other outcomes. Most of the trials found promising results of craving and/or use reduction with repetitive TMS (rTMS). Future interventions should consider the use of TMS as part of rehabilitation therapies. Game Addiction Scale for Adolescents: Arabic Version Validation Objectives: This study is aimed to translate the game addiction scale for adolescents into Arabic language and to test reliability and validity of the Arabic version. The game addiction scale for adolescents was developed to measure computer and video game addiction based on the criteria of pathological gambling in DSM-IV. Methods: The scale has been translated into Arabic. The English and Arabic versions were compared by psychiatry experts to ensure consistency and then they were administered to bilingual individuals who played computer and video games. Finally, the Arabic version was distributed among 50 school students, aged 10 to 19 years, who played computer and video games. Results and Conclusions: The data were collected from school students. The statistical analysis of the Arabic version of game addiction scale for adolescents showed that the Arabic/English validity was satisfactory, with proper internal consistency and reliability. Alcohol Consumption by Older People in Brazil: A Systematic Review of Population-based Studies Introduction: Given the rapid population aging taking place in countries like Brazil and in many other countries, understanding patterns of alcohol consumption by older people and the associated factors are important. Methods: The databases MEDLINE, Embase, and LILACS were searched for population-based studies on the prevalence of current alcohol consumption among Brazilians aged over 60. Results: Eight eligible studies were identified. Two studies reported data on binge drinking, with one national study finding a prevalence of 10.3%, while the other (male subjects only) found higher prevalences (27.1% and 13.7% at 2 sites). Heavy drinking was estimated in 4 studies with prevalences varying from 2.9% to 7.3%. Alcohol dependence was estimated in 3 studies, 1 used the DSM-IV diagnosis criteria and found a prevalence of 3.8%, while the other 2 used screening tools and found higher prevalences of 8.2% and 9.2%. Being male and younger were associated with several of the above patterns of alcohol consumption. Higher education was associated with binge and heavy drinking, and low education and socioeconomic status with alcohol dependence. Discussion/Conclusions: These findings show that in Brazil problems related to alcohol use by the elderly remain relatively unknown. There was a high heterogeneity of methodologies in the studies, making it difficult to summarize the findings and produce prevalence estimates for the different patterns of consumption. More homogenous studies using similar definitions of patterns of alcohol consumption are required to allow comparisons to be made between different Brazilian regions and other countries. Profile of Help-seeking Crack Cocaine Users in Brazil: A Comparison of 2 Cross-sectional Studies From 1997 and 2013 Objective: The purpose of this study was to compare the characteristics of treatment-seeking crack cocaine users in Brazil in 1996/1997 and 2012/2013. Methods: We analyzed data from 2 cross-sectional studies conducted 16 years apart. The first study (performed 1996-1997) included 133 crack users. The second study (performed 2012-2013) included 577 crack users. An interview based on the Intake Questionnaire and the Maudsley Addiction Profile was performed to examine sociodemographic characteristics and patterns of drug use. In both surveys, criminal and treatment history were collected. Results: The mean age of users increased from 27.3 years (SD=7.9) in 1997 to 30.8 years in 2013 (SD=7.7). The number of individuals with a high school diploma was >3 times higher in 2013, (11.7% vs. 38.9%). The mean time elapsed since first use was 3.9 years (SD=2.8) in 1997 versus 9.3 years (SD=5.8) in 2013. Other differences included higher unemployment and incarceration rates in the 1997 study. Conclusions: A change was detected in the profile of treatment-seeking crack cocaine users over the past 2 decades. Current patients appear to be older and use the drug more chronically, in addition to having a higher level of schooling and lower unemployment rates when compared with 1997 users. Clinic Payment Options as a Barrier to Accessing Medication-assisted Treatment for Opioid Use in Albuquerque, New Mexico Objectives: For patients with opioid addiction seeking treatment, an effective option is Medication-assisted Treatment (MAT). In Albuquerque, the city with the greatest number of people who use opioids in New Mexico, the demand for MAT exceeds the number of patients receiving treatment. The authors hypothesized that a primary factor in patients' ability to access treatment is clinic payment options, rather than the traditionally cited availability of providers. Methods: The authors conducted a survey assessing payment methods and corresponding availability in MAT programs for 53 of Albuquerque's ~70 providers. Results: The authors found a statistically significant (P<0.01) imbalance in treatment availability between insurance-accepting clinics (10.1% had ≥1 openings) and cash clinics (100% had ≥1 openings). Conclusions: These findings suggest that a lack of clinics accepting Medicaid and third party insurance may pose a significant treatment barrier. The authors thus conclude that more focus should be placed on increasing the number of clinicians and clinics accepting insurance.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

08:31

Myeloid Neoplasia and Other Leukemias No abstract available Unusual Presentation of Myeloid Sarcoma in a Patient With Usher Syndrome A 45-year-old woman with Usher syndrome, associated congenital deafness, progressive blindness due to retinitis pigmentosa, and latent autoimmune diabetes presented to the emergency department with malaise, dizziness, and pelvic pain following removal of an intrauterine device. A posterior vaginal wall mass was found on examination. Laboratory values demonstrated anemia, thrombocytopenia, and an elevated white blood cell count, raising concern for infection and potential onset of diabetic ketoacidosis. This prompted a peripheral blood smear review, which showed 60% monocytic blasts. A subsequent vaginal mass biopsy showed a myeloid sarcoma. Molecular studies demonstrated an NPM1 mutation in exon 12 without FLT3 mutation or internal tandem duplication. While a diagnosis of acute myeloid leukemia with mutated NPM1 was considered, cytogenetics revealed a complex karyotype with evidence of clonal evolution, consistent with acute myeloid leukemia with myelodysplasia-related changes. In addition to an unusual presentation of myeloid sarcoma, this case posed significant questions regarding management and pursuit of hematopoietic stem cell transplantation. Usher syndrome is genetically and clinically heterogeneous. While it is not known to be associated with increased risk of malignancy, mutation of genes associated with Usher syndrome has been identified in acute leukemia. Our case raises the question as to whether potential germline predisposition should be considered in a patient with a previously unassociated congenital syndrome. Chronic Myelomonocytic Leukemia in a Patient With a Germline Predisposition and Short Telomeres Myeloid neoplasms with germline predisposition are an increasingly recognized category within the World Health Organization classification. Detection requires a high degree of suspicion, with mounting awareness of clinically silent phenotypes and heterogeneous presentations, challenging diagnostic and laboratory testing considerations, need for surveillance of disease progression, and unique concerns in donor selection for stem cell transplantation. We describe the case of a patient who presented as a teenager with thrombocytopenia and was later diagnosed with chronic myelomonocytic leukemia, with eventual transformation to acute myeloid leukemia, which has relapsed after stem cell transplantation. She was found to have short telomeres and a TERT mutation, in addition to numerous features suggestive of a germline predisposition syndrome. These findings have not been specifically associated with chronic myelomonocytic leukemia and raise interesting questions about the associations between myelodysplastic/myeloproliferative neoplasms, telomere biology disorders, and the roles of specific myeloid mutations as drivers of disease. Next-Generation Sequencing Analysis in Posttransplant Relapsed Acute Myeloid Leukemia Reveals Clonal Evolution and Donor-Derived Germline Variant Indicating Bone Marrow Chimerism The era of next-generation sequencing (NGS) has led to a deeper understanding of the genetic complexity and heterogeneity of this disease, in addition to revealing mechanisms of disease relapse. Clinical NGS is becoming routine in clinical practice in both solid organ and hematologic malignancies to identify molecular markers of disease that might assist with diagnosis, prognosis, and the treatment of cancer. These tumor-specific markers also enable treatment response monitoring, as they serve as clonal markers unique to the disease. Continuous molecular monitoring also allows identification of disease recurrence with potentially new actionable mutations. This practice is complicated in the setting of allogeneic bone marrow transplant, as the admixtures of donor and recipient DNA pose unique challenges to NGS interpretation. This case highlights the importance of systematic methodological interpretation of NGS results to better understand the clinical significance and impact of new mutations discovered posttransplant and reveals another potential application of NGS for bone marrow engraftment analysis. Unclassifiable Myelodysplastic/Myeloproliferative Neoplasm With Hypocellularity: A Classification Conundrum Myelodysplastic/myeloproliferative neoplasm (MPN), unclassifiable (MDS/MPN-U), has clinical and morphologic features of both myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPNs), and does not meet diagnostic criteria for any other specific entity within MDS, MPN, or MPN, including therapy-related myeloid neoplasms, and cases evolving from a prior MDS or MPN. Diagnostic criteria for MDS/MPN-U include, among other specifications, a platelet count of greater than or equal to 450 × 10E9/L associated with bone marrow megakaryocytic proliferation. We present the case of a young adult patient with a several-year reported history of cytopenias, found to have thrombocytosis and 5% circulating blasts. Surprisingly, his bone marrow biopsy demonstrated hypocellularity (10%), with 5% to 10% blasts, myeloid hypoplasia, minimal fibrosis, and focal megakaryocytic dyspoiesis but no hyperplasia. The constellation of morphologic and clinical features presents a challenging differential diagnosis between MDS/MPN-U and MDS with excess blasts (as well as thrombocytosis). Molecular testing interestingly demonstrated an SF3B1 mutation, although no increased ring sideroblasts were found by iron staining. Cases such as these may prove instructive in refining our understanding of the MDS/MPN category, as well as its relationship to myelodysplasia and the complex molecular genetic landscape underlying myeloid neoplasia. Granulomatous Slack Skin T-Cell Lymphoma Manifesting as Ulcerative and Gangrenous Lesions With a Fatal Outcome: A Case Report and Review of the Literature Granulomatous slack skin is an extremely rare cutaneous T-cell lymphoma, which often pursues an indolent disease course. Clinically, it is characterized by areas of redundant and lax skin in flexural areas, with variable erythema. Histologic findings include granulomatous T-cell infiltrates with loss of elastic fibers and poikilodermic change. In this article, we report a patient with unusual rapidly progressive ulcerative and gangrenous skin lesions, leading to amputation and ultimately demise. We also review the literature on granulomatous slack skin with similarly aggressive clinical course and discuss the differential diagnosis. MYC Alteration by Chromothripsis Event in Aggressive High-Grade B-Cell Lymphoma Negative by Conventional Fluorescence In Situ Hybridization Analysis: A Case Report Double-hit and double-expressor phenotypes in lymphomas are characterized by activation of the expression of the MYC and BCL2 genes through diverse mechanisms including chromosomal translocations and amplifications. Herein, we report a high-grade B-cell lymphoma in a patient with evidence for a chromothripsis event (via chromosomal microarray methodology) at chromosome 8, resulting in a focal copy number gain of the MYC locus, not detected by conventional fluorescence in situ hybridization for MYC despite strong MYC expression by immunohistochemical analysis. Chromosome analysis from the biopsy was not successful because of an extensive tissue necrosis. Chromothripsis is suggested as another mechanism for the activation of MYC in non-Hodgkin lymphoma, resulting in aggressive disease course, and this case underscores the need for chromosomal microarray testing in select cases to identify aggressive biology. Unusual Cases of Hairy Cell Leukemia With Uncommon Immunophenotypes: A Diagnostic Challenge Hairy cell leukemia (HCL) is a rare indolent B-cell neoplasm with distinct morphologic and immunophenotypic features. Immunophenotypically, the neoplastic cells in HCL are strongly positive for B-cell markers, such as CD19, CD20, and CD22. They also characteristically express CD11c, CD25, CD103, and CD123, but lack CD5, CD10, and CD23. Uncommon immunophenotypes of HCL can pose diagnostic challenges. Here, we report 2 unusual cases of CD5-positive and CD10-positive HCL. Hairy Cell Leukemia Presenting as Presternal Soft Tissue Mass: A Case Report With Review of Literature Hairy cell leukemia (HCL) is an uncommon chronic lymphoproliferative disorder. Initial presentation frequently includes symptoms related to peripheral blood cytopenias. It can sometimes have atypical manifestations and can present at unusual sites. We report an unusual presentation of HCL as a presternal soft tissue mass in a 45-year-old man. His peripheral blood counts showed pancytopenia. There were no palpable lymph nodes or hepatosplenomegaly. CT-scan revealed a middle mediastinal mass with extension into the presternal soft tissue. Tissue core biopsy was taken and histopathologic findings confirmed the diagnosis of HCL. To our knowledge, this is the second reported case of HCL presenting as a presternal soft tissue mass. Although rare, HCL should be considered in the differential diagnosis of tumors involving extramedullary/extranodal sites including the soft tissue and bone, so the patient can get the utmost benefit for early diagnosis of a treatment responsive disease. Myeloid Sarcoma of the Urinary Bladder Associated With t(8;21): Case Report and Review of the Literature Myeloid sarcoma is a malignant neoplasm of myeloid lineage that occurs in extramedullary sites, frequently in patients with acute myeloid leukemia and other myeloproliferative and myelodysplastic syndromes. Myeloid sarcoma of the urinary bladder is exceptionally rare, and although the most common cytogenetic abnormality associated with this lesion is t(8;21)/RUNX-RUNX1T1, to the best of our knowledge, there are no previous reports of this in patients with bladder involvement. We report a case of a 30-year-old man with a urinary bladder mass, which was consistent with myeloid sarcoma with t(8;21). The importance of myeloid sarcoma of the bladder is that it could be misdiagnosed and must be differentiated from other poorly differentiated bladder tumors composed of round cells, mainly because it is a malignant neoplasm with a good response to treatment, which does not require surgery.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

08:31

Reversible Impaired Methotrexate Clearance After Platinum-Based Chemotherapy for Osteosarcoma Abstract: The authors present a case of an 18-year-old man with metastasized osteosarcoma, admitted for methotrexate (MTX) treatment combined with cisplatin and doxorubicin. During the first cycle, severe MTX toxicity was observed with increased MTX serum levels and delayed MTX clearance requiring rescue treatment with intensified leucovorin. In the following cycles, cisplatin and doxorubicin were discontinued, and MTX dose was reduced. The elimination half-life slowly improved over the following cycles suggesting a reversible cause responsible for reduced MTX clearance and toxicity during the first cycle. Cisplatin is well-known for its nephrotoxic effects and can induce reversible tubular injury. Previous treatment with cisplatin may well have been responsible for decreased MTX clearance, and combination treatment should be used with adequate monitoring of MTX levels. Other factors that may have contributed, such as urine alkalization, gene polymorphisms, and other drug–drug interactions are discussed. Generation and Validation of a Limited Sampling Strategy to Monitor Mycophenolic Acid Exposure in Children With Nephrotic Syndrome Background: Mycophenolate mofetil (MMF) plays an increasingly important role in the treatment of children with nephrotic syndrome, especially in steroid sparing protocols. Recent publications show the relationship of exposure to its active moiety mycophenolic acid (MPA) and clinical efficacy. Performance of full-time pharmacokinetic (PK) profiles, however, is inconvenient and laborious. Established limited sampling strategies (LSS) to estimate the area under the concentration (AUC) versus time curve of MPA (MPA-AUC) in pediatric renal transplant recipients cannot be easily transferred to children suffering from nephrotic syndrome, mainly because of the lack of concomitant immunosuppressive therapy. We therefore aimed for the generation and validation of a LSS to estimate MPA exposure to facilitate therapeutic drug monitoring in children with nephrotic syndrome. Methods: We performed 27 complete PK profiles in 23 children in remission [mean age (±SD):12.3 ± 4.26 years] to generate and validate an LSS. Sampling time points were before administration (C0) and 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours after the administration of MMF. MPA was measured by enzyme multiplied immunoassay technique. There was no concomitant treatment with calcineurin inhibitors. Results: Mean daily dose of MMF was 927 ± 209 mg/m2 of body surface area resulting in a mean MPA-AUC0-12 value of 59.2 ± 29.3 mg × h/L and a predose level of 3.03 ± 2.24 mg/L. Between-patient variability of dose-normalized MPA-AUC0-12 was high (coefficient of variation: 45.5%). Correlation of predose levels with the corresponding MPA-AUC0-12 was moderate (r2 = 0.59) in a subgroup of 18 patients (20 PK profiles, generation group). An algorithm based on 3 PK sampling time points during the first 2 hours after MMF dosing (estimated AUC0-12 = 8.7 + 4.63 × C0 + 1.90 × C1 + 1.52 × C2) was able to predict MPA-AUC with a low percentage prediction error (3.88%) and a good correlation of determination (r2 = 0.90). Validation of this algorithm in a randomized separate group of 6 patients (7 PK profiles, validation group) resulted in comparably good correlation (r2 = 0.95) and low percentage prediction error (5.57%). Conclusions: An abbreviated profile within the first 2 hours after MMF dosing gives a good estimate of MPA exposure in children with nephrotic syndrome and hence has the potential to optimize MMF therapy. Pharmacokinetics of Enteric-Coated Mycophenolate Sodium in Lupus Nephritis (POEMSLUN) Background: Mycophenolate mofetil or enteric-coated mycophenolate sodium (EC-MPS) and steroids are used for induction and maintenance therapy in severe lupus nephritis. Blood concentrations of mycophenolic acid (MPA), the active metabolite of these drugs, vary among patients with lupus nephritis. The objective of this study was to examine whether concentration-controlled (CC) dosing (through therapeutic drug monitoring) of EC-MPS results in a higher proportion of participants achieving target exposure of MPA compared with fixed-dosing (FD). An additional aim of the study was to evaluate the influence of CC dosing on clinical outcomes. Methods: Nineteen participants were randomly assigned either to the FD or CC group. All the participants were eligible to have free and total measurements of MPA over a period of 8–12 hours on 3 different occasions. Area under the concentration–time curve between 0 and 12 hours (AUC0-12) was calculated using noncompartmental methods. Dose of EC-MPS was titrated according to AUC0-12 in the CC group. Results: Thirty-two AUC0-12 measurements were obtained from 9 FD and 9 CC participants. Large inter-patient variability was observed in both groups but was more pronounced in the FD group. There were no significant differences between FD and CC participants in any pharmacokinetic parameters across the study visits, except for total C0 (FD 2.0 ± 0.3 mg/L versus CC 1.1 ± 0.3; P = 0.01) and dose-normalized C0 (FD 2.9 ± 0.2 mg/L/g versus CC 2.1 ± 0.7 mg/L/g; P = 0.04) at the second visit and total AUC0-12 (FD 66.6 ± 6.0 mg·h/L versus CC 35.2 ± 11.4 mg·h/L; P = 0.03) at the third visit. At the first study visit, 33.3% of the FD and 11.1% of the CC participants achieved the target area under the concentration–time curve (P = 0.58). From the second visit, none of the FD participants, compared with all the CC participants, achieved target AUC0-12 (P = 0.01). More CC participants achieved remission compared with FD participants (absolute difference of −22.2, 95% confidence interval JOURNAL/thdm/04.02/00007691-201912000-00003/math_3MM1/v/2019-11-14T070550Z/r/image-tiff 0.19 to 0.55; P = 0.62). The mean free MPA AUC0-12 was significantly lower in those who had complete remission. Conclusions: CC participants reached target AUC0-12 quicker. Larger studies are required to test clinical efficacy. Quality Assessment of Dried Blood Spots from Patients With Tuberculosis from 4 Countries Background: Dried blood spot (DBS) sampling is a blood collection tool that uses a finger prick to obtain a blood drop on a DBS card. It can be used for therapeutic drug monitoring, a method that uses blood drug concentrations to optimize individual treatment. DBS sampling is believed to be a simpler way of blood collection compared with venous sampling. The aim of this study was to evaluate the quality of DBSs from patients with tuberculosis all around the world based on quality indicators in a structured assessment procedure. Methods: Total 464 DBS cards were obtained from 4 countries: Bangladesh, Belarus, Indonesia, and Paraguay. The quality of the DBS cards was assessed using a checklist consisting of 19 questions divided into 4 categories: the integrity of the DBS materials, appropriate drying time, blood volume, and blood spot collection. Results: After examination, 859 of 1856 (46%) blood spots did not comply with present quality criteria. In 625 cases (34%), this was due to incorrect blood spot collection. The DBS cards from Bangladesh, Indonesia, and Paraguay seemed to be affected by air humidity, causing the blood spots not to dry appropriately. Conclusions: New tools to help obtain blood spots of sufficient quality are necessary and environmental specific recommendations to determine plasma concentration correctly. In addition, 3% of the DBS cards were rejected because the integrity of the materials suggesting that the quality of plastic ziplock bags currently used to protect the DBS cards against contamination and humidity may not be sufficient. Nonparametric Population Pharmacokinetic Modeling of Isoniazid in Colombian Patients With Tuberculosis Background: Isoniazid (INH) is a first-line antituberculosis (TB) agent with a pharmacokinetic profile characterized by high interindividual variation; however, population pharmacokinetic studies in patients with TB are scarce. The aim was to develop a population model for INH in Colombian patients with TB suitable for predicting drug exposure and assessing the probability of target attainment of pharmacodynamic goals. Methods: Ten hospitalized adult patients with TB undergoing INH treatment were recruited. After an 8-hour fasting, subjects took 300 mg of INH, and 10 samples were taken from 0 to 12 hours. INH was quantified by high-performance liquid chromatography–UV, and data were analyzed with the Pmetrics R package software. A Monte Carlo simulation with the model parameters was run to determine the probability of target attainment for optimal efficacy. Results: The best model included 2 compartments, first-order absorption (Ka), delayed absorption (Tlag), and linear clearance (CL). Median Tlag was 0.25 hours, 5.54 hour−1 for Ka, JOURNAL/thdm/04.02/00007691-201912000-00005/math_5MM1/v/2019-11-14T070550Z/r/image-tiff for CL, JOURNAL/thdm/04.02/00007691-201912000-00005/math_5MM2/v/2019-11-14T070550Z/r/image-tiff for the volume of the central compartment (Vc), 1.04 L/h for intercompartmental clearance (Q), and 788 L for the volume of the peripheral compartment (Vp). CL and Vc were allometrically scaled on basis of the normalized body weight. Conclusions: The Monte Carlo simulation indicated that 300 mg of INH per day is appropriate for Mycobacterium tuberculosis strains with minimal inhibitory concentration (MIC) up to 0.03 mg/L (target: area under the concentration–time curve/MIC >597); however, to cover strains with MIC up to 0.125 mg/L (80% of clinical isolates), a dose of 900 mg per day would be required. Comparison of the Area Under the Curve for Vancomycin Estimated Using Compartmental and Noncompartmental Methods in Adult Patients With Normal Renal Function Background: Vancomycin pharmacokinetics are best described using a 2-compartment model. However, 1-compartment population models are commonly used as the basis for dose prediction software. Therefore, the validity of using a 1-compartment model to guide vancomycin drug dosing was examined. Methods: Published plasma concentration–time data from adult subjects (n = 30) with stable renal function administered a single intravenous infusion of vancomycin were extracted from previous studies. The vancomycin area under the curve (AUC0–∞) was calculated for each subject using noncompartmental methods (AUCNCA) and by fitting 1- (AUC1CMT), 2- (AUC2CMT), and 3- (AUC3CMT) compartment infusion models. The optimal model fit was determined using the Akaike information criterion and visual inspection of the residual plots. The individual compartmental AUC0–∞ values from the 1- and 2-compartment models were compared with AUCNCA values using one-way repeated measures analysis of variance. Results: The mean (±SD) AUC estimates were similar for the different methods: AUCNCA 180 ± 86 mg·h/L, AUC1CMT 167 ± 79 mg·h/L, and AUC2CMT 183 ± 88 mg·h/L. Despite the overlapping AUC values, AUC2CMT and AUCNCA were significantly greater than AUC1CMT (P < 0.05). The 3-compartment model was excluded from the analysis because of the failure to converge in some instances. Conclusions: Dose prediction software using a 1-compartment model as the basis for Bayesian forecasting underestimates drug exposure (estimated as the AUC) by less than 10%. This is unlikely to be clinically significant with respect to dose adjustment. Therefore, a 1-compartment model may be sufficient to guide vancomycin dosing in adult patients with stable renal function. Linezolid Dosing in Patients With Liver Cirrhosis: Standard Dosing Risk Toxicity Background: Limited data regarding altered linezolid pharmacokinetics in patients with liver cirrhosis are available. The objective of this study was to evaluate the pharmacokinetics, efficacy and safety of linezolid in cirrhotic patients. Methods: A case–control 1:1 study of patients undergoing linezolid therapeutic drug monitoring was conducted between January 2015 and June 2017. Cases with liver cirrhosis were matched with controls by age, body weight, comorbidities, renal function, and intensive care unit (ICU) admission. Results: Fifty-two patients were included, 26 in each group. Patients with Child–Pugh Scores A, B, and C were 1 (3.8%), 13 (50.0%), and 12 (46.2%), respectively. Cases had higher median linezolid trough plasma concentrations than controls [20.6 (17.4) versus 2.7 (11.3); P < 0.001)] and more frequently achieved an optimal pharmacodynamic index [26 (100%) versus 16 (61.5%); P = 0.002]. In addition, potentially toxic concentrations and treatment discontinuation due to overexposure and hematological toxicity were also more frequently seen in cirrhotic patients. Overall clinical cure rate was high (67.4%), and in-hospital mortality was 28.8%. No differences in clinical outcomes were observed between both groups. Conclusions: Linezolid showed a high clinical cure rate. Nevertheless, plasma concentrations and treatment discontinuation due to hematological toxicity were higher in cirrhotic patients. Liver cirrhosis may influence linezolid pharmacokinetics and question the use of standard doses. Therapeutic drug monitoring of linezolid would be valuable in these patients. Pharmacokinetic/Pharmacodynamic Analysis of Voriconazole Against Candida spp. and Aspergillus spp. in Allogeneic Stem Cell Transplant Recipients Background: To evaluate the adequacy of different dosing regimens of voriconazole for the prophylaxis of invasive candidiasis and aspergillosis in adult allogeneic stem cell transplant recipients by means of population pharmacokinetic (PK) modelling and simulation. Methods: Allogeneic stem cell transplant recipients receiving voriconazole were included in this observational study. A population PK model was developed. Three oral voriconazole-dosing regimens were simulated: 200, 300, and 400 mg twice daily. The pharmacodynamic target was defined as fAUC0–24/0.7. A probability of target attainment ≥90% was considered optimal. The cumulative fraction of response was defined as the fraction of patients achieving the pharmacodynamic target when a population of simulated patients is matched with a simulated population of different Candida spp. and Aspergillus spp. The percentage of patients with trough plasma concentrations at steady state (Ctrough) within the reference range (1–5.5 mg/L) was also calculated. Results: A 2-compartment PK model was developed using data from 40 patients, which contributed 237 voriconazole plasma samples, including trough and maximum concentrations. Voriconazole 200, 300, and 400 mg twice daily achieved probability of target attainment ≥90% for minimal inhibitory concentration values ≤0.25, ≤0.38, and ≤0.50 mg/L, respectively. The cumulative fraction of response for A. niger, A. versicolor, and A. flavus increased >10% when increasing voriconazole dose from 200 to 400 mg twice daily (from 72.5% to 89.5% for A. niger; from 77.7% to 88.7% for A. versicolor; and from 82.4% to 94.9% for A flavus). The percentage of patients with Ctrough within the reference range increased 15% when voriconazole dose was increased from 200 to 300 mg twice daily. Conclusions: The PK simulations in this study suggest that transplant recipients on voriconazole prophylaxis against invasive candidiasis or aspergillosis are likely to achieve the target concentrations associated with the desired treatment outcomes if the maintenance dose is 200 mg twice daily. However, Aspergillus spp. with high minimal inhibitory concentrations could require higher maintenance doses. Chinese Patients With Heart Valve Replacement Do Not Benefit From Warfarin Pharmacogenetic Testing on Anticoagulation Outcomes Background: Genotype-guided warfarin dosing has been shown in some randomized trials to improve anticoagulation outcomes in individuals of European ancestry; yet, its utility in Chinese patients with heart valve replacement remains unresolved. Methods: A total of 2264 patients who underwent heart valve replacement at Wuhan Asia Heart Hospital were enrolled in this study. Patients were randomly divided into 2 groups, namely, a genotype-guided and a traditional clinically guided warfarin dosing group. In the genotype-guided group (n = 1134), genotyping for CYP2C9 and VKORC1 (−1639 G→A) was performed using TaqMan genotyping assay. Warfarin doses were predicted with the International Warfarin Pharmacogenetics Consortium algorithm. Patients in the control group (n = 1130) were clinically guided. The primary outcome was to compare the incidence of adverse events (major bleeding and thrombotic) during a 90-day follow-up period between 2 groups. Secondary objectives were to describe effects of the pharmacogenetic intervention on the first therapeutic-target-achieving time, the stable maintenance dose, and the hospitalization days. Results: A total of 2245 patients were included in the analysis. Forty-nine events occurred during follow-up. Genotype-guided dosing strategy did not result in a reduction in major bleeding (0.26% versus 0.63%; hazard ratio, 0.44; 95% confidence interval, 0.13–1.53; P = 0.20) and thrombotic events (0.89% versus 1.61%; hazard ratio, 0.56; 95% confidence interval, 0.27–1.17; P = 0.12) compared with clinical dosing group. Compared with traditional dosing, patients in the genotype-guided group reached their therapeutic international normalized ratio in a shorter time (3.8 ± 2.0 versus 4.4 ± 2.0 days, P < 0.001). There was no difference in hospitalization days (P = 0.28). Conclusions: Warfarin pharmacogenetic testing according to the International Warfarin Pharmacogenetics Consortium algorithm cannot improve anticoagulation outcomes in Chinese patients with heart valve replacement. Prednisolone Concentrations in Plasma (Total and Unbound) and Saliva of Adult Kidney Transplant Recipients Background: Prednisolone displays significant pharmacokinetic variability and exposure–outcome relationships in renal transplant recipients, suggesting a role for drug monitoring in some scenarios. It is highly protein-bound, and the free form is pharmacologically active but cumbersome to measure. Saliva concentrations might reflect free plasma prednisolone and present an alternative measurement. The aim of this study was to examine the correlation between total and free plasma and saliva prednisolone in adult renal transplant recipients. Methods: Total and free plasma and saliva prednisolone concentrations were measured in 20 patients receiving oral prednisolone 1–2 months after transplant, between pre-dose and 12 hours post-dose. Prednisolone was determined using high-performance liquid chromatography mass spectrometric detection. The Pearson coefficient was used to assess the association between plasma and salivary prednisolone concentrations and area under the concentration–time curves (AUC0–12). Results: When considering all time points, the total and free plasma prednisolone concentrations correlated well (r2 = 0.81), but there was poor correlation between saliva and free (r2 = 0.003) and total (r2 = 0.01) plasma concentrations. When concentrations before the maximum free prednisolone plasma value were excluded, the correlation between free plasma and saliva concentrations improved (r2 = 0.57). There was a moderate correlation between free and total plasma prednisolone AUC0–12 (r2 = 0.62) using all time points, but a poor correlation between free and total plasma prednisolone AUC0–12 and saliva AUC0–12 (r2 = 0.07; r2 = 0.17). Conclusions: Total and free plasma prednisolone measurements correlated poorly with saliva measurements; however, correlation improved when concentrations early in the dosing interval were excluded.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

08:31

Candida Infections in Clinical Trials of Ixekizumab (Taltz), an Interleukin-17A Monoclonal Antibody, in Patients With Psoriasis or Psoriatic Arthritis Interleukin-17 mediates immunity against pathogens such as Candida. Ixekizumab, an anti-interleukin-17A antibody, showed efficacy treating psoriasis (PsO) and psoriatic arthritis (PsA). Detailed here are Candida infections from 11 PsO and three PsA ixekizumab studies. Overall, patients received 80-mg ixekizumab every 2 or 4 weeks for 12 weeks (PsO) or 24 weeks (PsA) and then every 4 weeks. Candida (high-level term), six Candida subcategories (oral, vulvovaginal, skin, esophageal, nail, and unspecific), and four fungal infections (esophagitis, oral, oropharyngitis, and vulvovaginal mycotic) were included. Patients were counted once per category for multiple events. Analysis included 5,689 patients with PsO (12,061.5 patient-years of exposure, median exposure = 883 days) and 1,118 patients with PsA (1,373.4 patient-years of exposure, median exposure = 309 days). Overall, Candida infections were low and occurred in 4.4% (PsO incidence rate = 2.1) and 3.1% (PsA incidence rate = 2.5); most were mild or moderate in severity. The average duration of moderate and mild Candida ranged from 33 to 105 days. Most Candida infections were single events, 74% and 91%, with median onset of 328 and 146 days for PsO and PsA, respectively. Five patients (four with PsO and one with PsA) were reported to have a severe infection. Oral, skin, and vulvovaginal Candida were the most frequently reported Candida infections. Leveraging Teledermatology for Patient Triage Nurses in outpatient settings face challenges balancing heavy patient caseloads while accommodating unplanned acute visits. Nurses also spend significant time triaging patients' symptoms on the telephone. Patients often find it difficult to accurately describe symptoms, and without accompanying images, unnecessary office visits are scheduled. Teledermatology, involving the exchange of digital images remotely between patient and provider, has shown promise in accurately triaging patients and decreasing unnecessary visits. At one outpatient dermatology site at a multisite comprehensive cancer center, a 6-month performance improvement initiative was conducted to evaluate the effectiveness of teledermatology using an electronic patient portal. Nurses instructed prescreened patients to send digital images via the portal. On the basis of image appearance and patients' symptoms, nurses provided assessment and education over the phone, and patients either kept their future appointments or came in for an earlier evaluation. More complex cases were escalated to the physician. This initiative reduced the number of unnecessary patient visits, which opened more visit slots for those with acute issues. Teledermatology improved overall efficiency of care, and patients and clinicians have reported satisfaction with the process. Safe and Effective Laser Hair Removal Treatments: A Literature Review for New Providers Objective The aim of this study was to review the current literature regarding safe and effective laser hair removal (LHR) treatments. Methods Significant and current studies (2008–2017) were retrieved through a series of searches conducted in CINAHL, Cochrane, and MEDLINE databases using Boolean terms/phrases. Pertinent results are explained in narrative form with supporting tables and figures. Results Today, there is a vast amount of current literature on the need for LHR treatments and on its side effects and comparative studies using various lasers on the market. There is an ongoing concern associated with the lack of standards and guidelines. Conclusion Practitioners interested in offering LHR within the primary care setting must verify that operating a Class 4 medical device is within their scope of practice. Despite the increased popularity of LHR treatments and the advancement of technology, there are limited up-to-date information on safe and effective treatment parameters and minimal information regarding the importance of patient education. More research is necessary to determine the efficacy of LHR treatments in both men and women of all ages and skin types. With no LHR guidelines in place, the best practice for LHR treatments is contained within this literature review using the most recent research available to date. Kava-Induced Ichthyosis Acquired ichthyosis is an uncommon finding in the outpatient dermatology clinic. This case portrays a presentation of ichthyosis induced by the medicinal drink, kava, which is becoming a more mainstream beverage in American culture. This case provides an overview of the clinical presentation of ichthyosis and a historical background on kava as well as recent studies on kava-induced ichthyosis or kava dermopathy. It also highlights the need to consider the use of herbal and alternative therapies when considering the underlying causes of skin disorders. White Plaques of the Posterior Buccal Mucosa Teledermatology is a term to describe the provision of dermatologic medical services through telecommunication technology. This is a teledermatology case of oral lichen planus. Scaled Papules in an HIV-Positive Patient Teledermatology is the term used to describe the provision of dermatologic medical services through telecommunication technology. The following is a teledermatology case of scaled papules in an HIV-positive patient. Diffuse Nonresolving Violaceous Plaques This is a case of a patient presenting with nonresolving violaceous plaques for over 12 years of duration. In addition to the skin findings, the patient notes progressive arthropathy and nail changes. A multiple-choice question is presented, and readers will be challenged to diagnose this patient based on the case presentation, symptoms, and patient history. An answer is given followed by a discussion of the diagnosis, clinical features, and therapeutic management. Use of 5-Fluorouracil "Chemowraps" as a Method of Field Therapy for Actinic Keratosis and Adjunctive Therapy for Squamous Cell Carcinoma Drugs are medications or substances that are used to modify physiologic responses and alleviate associated symptoms. In dermatology, medications and substances are utilized on a daily basis and include topical treatments to anesthetics in micrographic surgery to biologic-acting immunologic agents. The purposes of this section are to focus on drug, specifically how it works and how it is utilized, and to discuss routine alternatives (if available). In this column, we will focus on the uses, mechanism of action, adverse effects, and alternatives of 5-fluorouracil used in chemowraps for actinic keratoses and squamous cell carcinoma. Skin Test No abstract available

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

08:29

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Arterialized Posterior Interosseous Nerve Graft for Digital Neuroma Painful neuromas are not uncommon following nerve injury, and are especially bothersome in the hand, with severe cases resulting in significant disability. Outcomes of neuroma surgery are unpredictable regardless of technique. It is recognized that optimal soft tissue environment influences nerve healing more than the specific nerve graft technique, and it is in this context, we present a novel technique of transferring a posterior interosseous nerve graft along with vascularized synovial and fat tissue based on a branch of the posterior interosseous artery to provide healthy soft tissue for nerve healing of neuroma in continuity about the hand and digits. Combined Pedicled Vascularized and Wedge Nonvascularized Bone Graft for Treating Scaphoid Waist Nonunion With Humpback Deformity Pedicled vascularized bone graft (VBG) is a useful method in treating the scaphoid fracture nonunion, especially when the avascular necrosis exists. Humpback deformity is an important issue that we have to correct it during the treatment. We describe a method by using combined wedge non-VBG to correct the nonunion deformity when treating scaphoid nonunion with pedicled VBG. The wedge bone graft was harvested just proximal to the 2,3 intercompartmental supraretinacular artery VBG and was used as an inlay at the volar site to correct the humpback deformity, whereas the VBG was set at the dorsal site for bone bridging and blood supply. We also present our results of 10 patients with scaphoid fracture nonunion and humpback deformity treated with this method. Bone healing was achieved and the lateral intrascaphoid angles could be improved in all the 10 patients. Functional outcomes, including the Visual Analog Pain Scale for pain during activity, grip strength, the shortened Disabilities of the Arm, Shoulder, and Hand questionnaire (QuickDASH), and the modified Mayo Wrist Scores, were significantly improved. Fixation of a Type 3 Flexor Digitorum Avulsion Injury This article describes a novel technique for flexor digitorum profundus (FDP) avulsion injuries, useful for Leddy Packer type 3, 4, and 5 injuries. Multidirectional stability is achieved with combination pull-out suture, which neutralizes the deforming force of FDP, and cerclage wire, which holds the bone fragment in an anatomic position and provides interfragmentary compression. Traditional techniques such as interosseous wires, Kirschner wires, or plating risk fragment comminution and loss of reduction due to proximal pull of FDP as demonstrated in this case report of failed Kirschner-wire fixation. The technique presented here eliminates the risk of avulsion fragment comminution and provides stable fixation that allows for early mobilization. Steindler Flexorplasty: A Description of Current Technique and Case Series This year marks the 100th anniversary of Dr Steindler's original report of a proximal transfer of the flexor pronator mass to restore elbow flexion. The authors present their updated surgical technique to perform the Steindler flexorplasty. In this procedure, the flexor-pronator mass origin on the medial epicondyle is transferred proximally to the anterior humerus to restore elbow flexion. They also report a retrospective case series of patients from 2007 to 2017 who underwent a Steindler flexorplasty at their institution to restore elbow flexion. In the series, 8 of 9 patients achieved at least 90 degrees of active antigravity (M3) or greater elbow flexion. Outcomes following the Steindler flexorplasty have been reported in the literature over the course of the past 100 years. Although alternative techniques to improve elbow flexion have been developed and performed over the last century, this time tested procedure remains a powerful reconstructive option. Anteromedial Release for Posttraumatic Flexion-pronation Contracture of the Wrist: Surgical Technique Wrist stiffness can be a complication of trauma. A small percentage of patients fail to improve with nonoperative management and require operative intervention to regain range of motion and function. These group of patients can present with a soft tissue flexion-pronation contracture, which is hypothesized to be caused by capsular contraction of the distal radioulna joint, musculotendinous contracture of the flexor carpi ulnaris, contracture of the volar ulnar carpal ligaments and of the pronator quadratus muscle. This complication significantly restricts functional dart-thrower's range of motion and is highly disabling. A surgical option to manage this condition is release of pathologic structures with an anteromedial approach to the wrist. We describe a safe, effective, and reproducible technique to treat these patients. A Novel External Fixation Technique for Injuries of the Proximal Interphalangeal Joint Digital external fixation is often used for the management of complex injuries involving the proximal interphalangeal joint, including pilon fractures of the middle phalanx base and unstable fracture-dislocations. Several dynamic "homemade" constructs have been described which utilize only K-wires and rubber bands and allow early range of motion within the construct. Although these constructs are inexpensive and their application is fairly straightforward, their designs pose a few potential problems when the construct is stressed during rehabilitation efforts. These designs utilize a blocking K-wire which relies on pin-to-pin contact to maintain reduction and creates unnecessary friction that can impede motion and result in pin loosening in bone. Furthermore, rubber band rupture can occur and destabilizes the construct. Here we present a novel technique which utilizes only K-wires and K-wire caps, provides adequate joint distraction and stabilization throughout the arc of motion, and avoids the aforementioned pitfalls of existing designs. Triquetrum Excision in Radioscapholunate Arthrodesis for Posttraumatic Radiocarpal Osteoarthritis With Ulnar Impaction Syndrome Dependent on fracture type, concomitant carpal injuries, and operative treatment, distal radius fractures can lead to symptomatic radiocarpal osteoarthritis. In addition, radial shortening can cause ulnar impaction syndrome. Radiocarpal arthrodesis and ulnar shortening osteotomy are known and frequently applied surgical procedures for each of those pathologies. There are limited data concerning treatment options for a combined disorder. The presented technique in this article demonstrates that radioscapholunate arthrodesis with distal pole scaphoidectomy and total triquetrum excision successfully treats both symptomatic radiocarpal osteoarthritis and ulnar impaction syndrome without further surgery on the ulna. Extra-articular Corrective Osteotomy With Bone Grafting to Achieve Lengthening and Regain Alignment for Distal Radius Fracture Malunion Surgical correction of the distal radius fracture malunion is challenging because of the 3-dimensional deformity. We propose a method by using the Kapandji intrafocal pinning in corrective osteotomy for treatment of the distal radius fracture malunion to facilitate the alignment correction while using the bone graft to restore the radial length. The surgery was started with the osteotomy from a volar approach, and the osteotomy gap was expanded gradually. Then, allobone grafting was performed to maintain the corrected radial length. We used the Kapandji intrafocal pinning dorsally to provide dorsal supporting force and radially to correct the radial inclination. Finally, a volar plate was used to buttress and push the distal fragment to fit as to regain the correct volar tilt. We enrolled 10 patients of distal radius fracture malunion with a mean age of 59.3 years. All patients had bone healing within 3 months after surgery. The mean lengthened distance was 5 mm. The radial inclination and volar tilt could be corrected with improved functional results. Anatomic Considerations and Reconstruction of the Thumb Flexor Pulley System Disruption to the flexor pulley system of the thumb is an infrequent but devastating injury that can lead to significant compromise in both strength and function. Acute rupture leads to pain, weakness, reduced range of motion (ROM), and potential bowstringing of the flexor tendons. Conservative treatment with a pulley ring should be considered in all patients. However, failure of conservative treatment and bowstringing of the thumb are indications for operative intervention. Reconstruction of the oblique pulley system can be performed either in situ or using a free palmaris longus graft. Care should be taken to identify the neurovascular bundles to avoid compression during the reconstruction. Conscious sedation protocols augmented by ultrasound-guided sheath blocks allow the patient to actively and strongly contract the flexor pollicis longus tendon intraoperatively to appropriately tension the construct for optimal results. Rehabilitation should be performed in a stepwise manner beginning with early passive ROM, active ROM, and finally strengthening at around 8 weeks postoperative.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

08:28

The Role of Positron Emission Tomography/Magnetic Resonance Imaging in Gynecological Malignancies Accurate oncological staging for early detection is of utmost importance in patient care and increasing the overall patient survival outcome. Hybrid imaging in the form of positron emission tomography (PET)/computed tomography has been successfully implemented in oncological imaging and, where available, has been used consistently in patients with gynecologic malignancies. The implementation of PET/magnetic resonance imaging (MRI) enables high-quality assessment of gynecological malignancies by combining the diagnostic advantages of metabolic information of PET along with the high-resolution anatomical and functional information from the MRI to provide precise information about staging, recurrence, and metastases. This article will review the various applications of PET/MRI in gynecological cancer. Ovarian Cancer Genetics and Implications for Imaging and Therapy Ovarian cancer is the second most common gynecologic malignancy in the United States. Ovarian cancer has a dismal prognosis when diagnosed at an advanced stage. Therapy for these cancers is determined not only by stage but also by their heterogeneous pathologic features, genetic mutations, and biology. In this review, we will discuss types of epithelial ovarian cancer, and their associated genetic mutations and the implications for imaging and treatment. Von Meyenburg Complex: Current Concepts and Imaging Misconceptions Von Meyenburg complexes, also known as biliary hamartomas, are ductal plate malformations that are usually diagnosed on imaging studies when there are multiple as small hepatic cysts. However, because of variations in histology, they actually have a wide spectrum of imaging appearances ranging from solid, to mixed solid and cystic, to cystic lesions. The objective of the review is to provide up-to-date information about the embryopathogenesis of von Meyenburg complexes, their imaging appearances, diagnostic pitfalls, and clinical significance. Combined Qualitative and Quantitative Assessment of Low-Attenuation Renal Lesions Improves Identification of Renal Malignancy on Noncontrast Computed Tomography Objective The objective of this study was to assess renal lesions measuring less than 20 Hounsfield units (HU) on noncontrast computed tomography (NCT). Methods Twenty-one (18.1%) of 116 consecutive pathologically proven renal cell carcinomas measured less than 20 HU on NCT and were compared with 40 confirmed benign cysts also measuring less than 20 HU. All lesions were assessed qualitatively (heterogeneous or homogenous) by 3 blinded readers and quantitatively with commercially available textural analysis software. Finally, a combined assessment was performed. Results Qualitative assessment performed well (sensitivity, 76%–90%; specificity, 70%–88%). Quantitative assessment revealed mean positive pixels as having the highest performance (area under the curve, 0.912; sensitivity, 90%; specificity, 80% at a cutoff value of 21). The combined assessment, using the mean positive pixel cutoff, improved the sensitivity (reader 1, 100%; reader 2, 95%; and reader 3, 95%). Conclusion Qualitative and quantitative assessments have relatively good performance, but the combination can nearly eliminate renal cell carcinomas being missed on NCT. Monoexponential and Biexponential Fitting of Diffusional Magnetic Resonance Imaging Signal Analysis for Prediction of Liver Fibrosis Severity Objective The objective of this study is to compare the value of monoexponential and biexponential approach to the diffusion-weighted magnetic resonance imaging signal in the prediction of the liver fibrosis. Methods Forty patients with hepatitis C were included. Quantification of the apparent diffusion coefficient (ADC) and pure molecular diffusion (D), pseudodiffusion (D*), and perfusion fraction (f) was performed using 9 b values (b = 0, 20, 50, 100, 200, 400, 600, 800, 1000 s/mm2). Results Significant fibrosis was found in 14 subjects. Monoexponentally derived ADC parameters were significantly correlated. Apparent diffusion coefficient calculated from all b values and ADC based on high b values were significantly related to the fibrosis grade (P < 0.02), and none of intravoxel incoherent motion parameters presented such an association. Apparent diffusion coefficient based on high b values was the best predictor of significant fibrosis with area under the curve of 0.81, sensitivity of 0.57, and specificity of 0.92. Conclusion Intravoxel incoherent motion parameters did not allow for prediction of the liver fibrosis. Apparent diffusion coefficient calculated based on high b values presents considerable specificity in predicting significant fibrosis. Imaging Features of Sclerosing Angiomatoid Nodular Transformation in Spleen Purpose The purpose of this study was to evaluate the features of sclerosing angiomatoid nodular transformation (SANT) in spleen on the imaging of computed tomography (CT) and magnetic resonance (MR). Materials and Methods From July 2006 to April 2017, 12 patients with SANT confirmed by pathology were evaluated in a retrospective study. Eight patients were with CT imaging only, 2 patients were with MR imaging only, and 2 patients were with both CT and MR. Three professional senior radiologists analyzed the imaging features on CT and MR. The main characteristic analysis included size, margin, density, signal intensity, and enhancement pattern. The significant enhancement was defined as the degree of enhancement of lesion that is higher than the surrounding spleen parenchyma, and the mild enhancement was defined as the degree of enhancement of lesion that is lower than the surrounding spleen parenchyma. Results All the 12 patients (5 men, 7 women; mean age, 45.8 years; age range, 21–62 years) presented as single lesion without special clinical symptoms. The range of lesions on diameter was from 25 to 80 mm. On CT images, 9 (90%) of 10 presented as hypodense in comparison with the parenchyma of spleen, 1 (10%) of 10 presented as isodense, and calcification was observed in 4 (40%) of 10 cases. On MR images, 4 (100%) of 4 manifested heterogeneous hypointensity on in-phase sequence and 3 (75%) of 4 performed as isointensity on out-of-phase sequence of T1-weighted. On the sequences of T2-weighted and diffusion-weighted image, 4 (100%) of 4 showed hypointensity. On CT and MR enhancement images, the number of significant enhancement and mild enhancement was 2 and 10, respectively. Seven (58%) of 12 showed progressive enhancement with the pattern of "spoke-wheel." Conclusions Imaging features on CT and MR have a high diagnostic value for SANT, especially when CT combined with MR examination. Whole-Body Computed Tomography Using Low-Dose Biphasic Injection Protocol With Adaptive Statistical Iterative Reconstruction V: Assessment of Dose Reduction and Image Quality in Trauma Patients Aim This study aimed to evaluate potential dose savings on a revised protocol for whole-body computed tomography and image quality after implementing Adaptive Statistical Iterative Reconstruction V (ASiR-V) algorism for trauma patients and compare it with routine protocol. Materials and Methods One hundred trauma patients were classified into 2 groups using 2 different scanning protocols. Group A (n = 50; age, 32.48 ± 8.09 years) underwent routine 3-phase protocol. Group B (n = 50; age, 35.94 ± 13.57 years) underwent biphasic injection protocol including unenhanced scan for the brain and cervical spines, followed by a 1-step acquisition of the thorax, abdomen, and pelvis. The ASiR-V level was kept at 50% for all examinations, and then studies were reconstructed at 0% ASiR-V level. Radiation dose, total acquisition time, and image count were compared between groups (A and B). Two radiologists independently graded image quality and artifacts between both groups and 2 ASiR-V levels (0 and 50%). Results The mean (±SD) dose-length product value for postcontrast scans in group A was 1602.3 ± 271.8 mGy · cm and higher when compared with group B (P < 0.001), which was 951.1 ± 359.6 mGy · cm. Biphasic injection protocol gave a dose reduction of 40.4% and reduced the total acquisition time by 11.4% and image count by 37.6%. There was no statistically significant difference between the image quality scores for both groups; however, group A scored higher grades (4.62 ± 0.56 and 4.56 ± 0.67). Similarly, the image quality scores for both ASiR-V levels in both groups were not significantly different. Conclusions Biphasic computed tomography protocol reduced radiation dose with maintenance of diagnostic accuracy and image quality after implementing ASiR-V algorism. Effective Radiation Dose Reduction in Computed Tomography With Iterative Reconstruction in Patients With Urinary Stone Purpose This study aimed to prospectively compare the image quality and visibility of urinary stone on computed tomographic (CT) images at multiple radiation exposure levels from the same patient reconstructed with sinogram-affirmed iterative reconstruction (SAFIRE). Methods This study included 760 patients with urinary stone who underwent CT with simultaneous acquisition at 6 exposures per patient (100% filtered back projection, 75%, 50%, 37.5%, 25%, and 12.5% SAFIRE). Two radiologists independently assessed overall image quality, noise, and stone visibility by using a 5-point scale. Quantitative measurements, including the CT number, image noise, signal-to-noise ratio, contrast-to-noise ratio (CNR), and corresponding figure of merit (FOM), were compared for 100% versus 5 other radiation doses. Results Qualitative overall image quality, noise, and stone visibility according to the location were not inferior at 37.5% exposure compared with 100% exposure, except for the visualization of smaller stones <3 mm. The signal-to-noise ratio and CNR of CT images were increased at 50% exposure compared with 100% exposure. Computed tomographic images at 37.5% exposure reconstructed with SAFIRE had significantly more noise and a lower CNR compared with CT images reconstructed with filtered back projection, based on FOMnoise and FOMCNR. The size-specific dose estimation was 4.1 ± 0.8 mGy at 37.5% exposure. Conclusion Computed tomography performed at 37.5% exposure with SAFIRE may be diagnostically acceptable for the detection of clinically relevant stone. Nonhemorrhagic Adrenal Infarction in Pregnancy: Magnetic Resonance Imaging and Computed Tomography Evaluation We present the case of unilateral nonhemorrhagic adrenal infarct in a 29-week pregnant 21-year-old woman. The patient presented with right upper quadrant pain, nausea, and vomiting. Ultrasonography of the right upper quadrant and appendix was negative for pathology. Magnetic resonance imaging of the abdomen demonstrated a right nonhemorrhagic adrenal infarct, subsequently confirmed with limited computed tomography of the upper abdomen. This case discusses the clinical presentation and pertinent imaging findings of adrenal infarction in pregnancy. Gastric Hepatoid Adenocarcinoma: Differentiation From Gastric Adenocarcinoma With Dynamic Contrast-Enhanced Computed Tomographic Findings Purpose This study aimed to describe the computed tomographic (CT) findings of gastric hepatoid adenocarcinoma (GHA) and determine features distinguishing it from gastric adenocarcinoma (GA). Methods Computed tomographic images of pathologically verified GHA (n = 11) and GA (n = 38) were retrospectively reviewed. α-Fetoprotein (AFP), carcinoembryonic antigen (CEA), and CT findings were assessed in our study. Computed tomographic findings included the location, distribution, growth pattern, ulceration, thickness of gastric wall, enhancement pattern, and the ratio of lesion attenuation to aorta CT attenuation. Short diameter of the metastatic lymph nodes, mean short diameter of metastatic lymph nodes, and the ratio of the number of enlarged lymph node on CT to the number of metastatic lymph nodes pathologically were measured and calculated. Data were compared using the χ2 and Student t tests; significant CT criteria were identified using receiver operating characteristic curve. Results α-Fetoprotein, CEA, and CT findings, including the longest short diameter, the mean short diameter, the ratio of the number of enlarged lymph node on CT to the number of metastatic lymph nodes pathologically, the lesion in arterial phase minus portal venous phase, and the lesion/aorta ratio, were statistically significant predictors for the differentiation of GHA from GA (P < 0.05). When only the aforementioned CT findings were used as criteria, the sensitivity and specificity for diagnosing GHA were 82.86% and 90.91%, respectively. When AFP, CEA, and CT findings were used as criteria, sensitivity of 97.14% and specificity of 90.91% were achieved. Conclusions Elevated serum AFP level and CT findings could distinguish GHA and GA with a high degree of accuracy.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Rare bleeding disorders and advances in gene therapy Rare bleeding disorders usually begin in childhood and manifest as varying degrees of bleeding, which can be life-threatening in severe cases. With the development of gene editing technology, it is expected that hereditary coagulation factor disorders will someday be fundamentally cured by gene therapy. On account of their rarity, comprehension of these diseases is essential for the application of new treatment strategies. We have compiled the features of some newly discovered mutations of prothrombin, factor VII, and factor X in recent years. In addition, this review introduces the advances and obstacles in gene therapy. Anticoagulant activity of krait, coral snake, and cobra neurotoxic venoms with diverse proteomes are inhibited by carbon monoxide Background A phenomena of interest is the in vitro anticoagulant effects of neurotoxins found in elapid venoms that kill by paralysis. These enzymes include phospholipase A2 (PLA2), and it has recently been demonstrated that carbon monoxide inhibits the PLA2-dependent neurotoxin contained in Mojave rattlesnake type A venom. The purpose of this investigation was to assess if the anticoagulant activity of elapid venoms containing PLA2 and/or three finger toxins could be inhibited by carbon monoxide. Methods Venoms collected from Bungarus multicinctus, Micrurus fulvius, and five Naja species were exposed to carbon monoxide via carbon monoxide releasing molecule-2 prior to placement into human plasma. Coagulation kinetics were assessed via thrombelastography. Results Compared with plasma without venom addition, all venoms had significant anticoagulant effects, with a 160-fold range of concentrations having similar anticoagulant effects in a species-specific manner. Carbon monoxide significantly inhibited the anticoagulant effect of all venoms tested, but inhibition was not complete in all cases. Conclusion Given that individual neurotoxin activity often depends on intact activity that includes anticoagulant action, it may be possible that carbon monoxide inhibits neurotoxicity. Future investigation is justified to assess such carbon monoxide mediated inhibition with purified neurotoxins in vitro and in vivo. Perioperative safety and haematostatic efficacy of a new bypassing agent pd-FVIIa/FX (Byclot) in haemophilia patients with high-responding type inhibitors The novel agent pd-FVIIa/FX is a 1 : 10 protein weight mixture of activated factor VII (FVIIa) and factor X (FX) derived from donated blood plasma. A phase III clinical trial of pd-FVIIa/FX revealed high efficacy for bleeding episodes in haemophilia patients with inhibitors. However, up to now, only one case of this new agent being used for surgery had been reported. The objective of this study is to evaluate the perioperative haemostatic efficacy and safety of pd-FVIIa/FX in haemophilia patients with inhibitors. We retrospectively reviewed 25 operation charts from 14 haemophilia patients with high-responding inhibitors using pd-FVIIa/FX during the perioperative period. Efficacy was evaluated by attending physicians and results divided into four groups (excellent, good, fair, and poor). The operation chart was provided by nine Japanese medical institutes with expertise in haemophilia management. Out of the total of 25 surgical procedures, 44% (11/25) were classified as major surgery and the remainders were minor surgeries. In all of the surgeries but one, rFVIIa and/or APCC were administered in combination or sequential method. In all cases except one, the haemostatic efficiency rate was judged as excellent or good by treating physicians for an overall efficacy rate of 96%. No thrombotic adverse effects were reported. This study's results suggest that both combination and sequential therapy of pd-FVIIa/FX and other bypassing agents are well tolerated and effective for the control of perioperative bleeding in haemophilia patients with high-responding inhibitors. Plasma phenotypes of protein S Lys196Glu and protein C Lys193del variants prevalent among young Japanese women Protein S Tokushima (p.Lys196Glu) and two protein C gene variants (p.Arg189Trp, p.Lys193del) are hereditary thrombophilia in Japanese and Chinese populations, respectively; however, their diagnosis by plasma analyses is difficult because of the type II deficiency phenotype. Three gene variant genotypes were examined in young Japanese women (n = 231). Plasma total protein S activity and total protein S antigen levels were measured using a total protein S assay system, protein C and protein S activities by clot-based methods, and protein C and free protein S antigen levels by latex agglutination methods. protein S Tokushima (p.Lys196Glu) and protein C p.Lys193del variants were prevalent among participants with allele frequencies of 1.08 and 0.86%, respectively, whereas any carrier of protein C p.Arg189Trp variant was not identified. The plasma phenotype of the type II deficiency of protein S Tokushima heterozygotes was demonstrated by decreased total protein S activity with a normal total protein S antigen level; however, the protein C activities of protein C p.Lys193del heterozygotes were within reference intervals, whereas their protein C antigen levels were elevated. We compared the diagnostic accuracy of the total protein S activity/total protein S antigen ratio for identifying protein S Tokushima heterozygotes with that of the clot-based protein S activity/free protein S antigen ratio and found that sensitivity and specificity of 100% each was only achieved by the former. Protein S Tokushima and protein C p.Lys193del are prevalent among young Japanese women, and a plasma analysis using the total protein S assay system is more accurate than the clot-based protein S activity/free protein S antigen ratio for diagnosing protein S Tokushima carriers. Mixing-based inhibitor screening in haemophilia A: challenges in interpretation Inhibitor development in haemophilia A patients is a dreaded complication of factor VIII (FVIII) replacement therapy. With increasing use of FVIII replacement therapy, there is an imperative need for cost-effective and standardized screening. To evaluate the efficacy of mixing-based inhibitor screening (MBIS) in the detection of FVIII inhibitors and to assess the best cut-off values for MBIS. Forty inhibitor positive and 40 inhibitor negative haemophilia A patients, diagnosed by standard criteria, with detailed clinical, haematological and on-demand treatment records were included. MBIS was evaluated in all 80 cases and a classical Bethesda assay and Nijmegen modification of Bethesda assay (NBA) were used as gold standards for inhibitor diagnosis. Classical Bethesda assay missed eight cases, most with low titres, which were confirmed by NBA. A systematic analysis of cut-offs for MBIS using a receiver operating characteristic curve fixed the cut-off at more than 5 s. MBIS detected 36 out of 40 inhibitor positive haemophilia A patients with a sensitivity, specificity, PPV and NPV of 90.0, 95, 94.7, 90.5%, respectively, whereas at the conventional cut-off of more than 10 s, MBIS detected only 25 of 40 cases with a low sensitivity of 62.5%. The likelihood ratio of a positive test was 11. The false-negative haemophilia A patients had low titres from 1.6 to 4.2 BU/ml. MBIS at a cut-off of 5 s can be considered as an effective screening test in low-resource situations. In clinical situations and in cases with clinical evidence of inhibitors we recommend that a direct NBA should be done. Congenital factor XI deficiency, complete genotype and phenotype of two Iranian families Congenital factor XI (FXI) deficiency is a mild trauma-related bleeding disorder with estimated worldwide prevalence of one per 1 million. The disorder is less frequent in Iran and a few studies have been performed on Iranian patients. In the current study, we assessed molecular, laboratory and clinical features of two Iranian patients with congenital FXI deficiency and their families. Clinical features and demographic data of the patients were assessed by the physician and a staff member trained specifically to deal with patients with bleeding disorders. FXI activity and antigen assays were performed for seven members of the two families and genotyping was performed by direct sequencing of all F11 gene exons and intron-exon boundaries as well as the untranslated regions. Five members of the two families were affected by FXI deficiency. Both patients experienced prolonged epistaxis, whereas other family members were asymptomatic. Two gene defects were observed in the patients and their families. Two disease-causing mutations were c.943G>A (p.Glu315Lys) missense and the four-nucleotide deletion (g.27849-27852del) in exon 15. The gene deletion was observed in homozygote state in the patient with severe FXI deficiency (FXI activity <1%) and heterozygote state in the parent, whereas the c.943G>A mutation was detected in heterozygote state and was accompanied by epistaxis in the patient. FXI deficiency is a mild bleeding disorder that is caused by heterogeneous molecular defects. Genetic analysis of a pedigree with hereditary coagulation factor XI deficiency To identify potential mutations of F11 gene in a family with hereditary coagulation factor XI (FXI) deficiency and explore the molecular pathogenesis. The FXI activity and FXI antigen were tested with clotting assay and ELISA, respectively. The FXI gene was amplified by PCR with direct sequencing. Three bioinformatics softwares were used to study the conservatism and harm of the mutation. The proband had a prolonged activated partial thromboplastin time (84.2 s), whose FXI activity and FXI antigen were 3.0 and 8.6%. Gene sequencing revealed that the propositus carried a heterozygous nonsense mutation c.738G>A in exon 7 resulting in a p.Trp228stop and deletions mutation c.1325delT in exon 12 resulting in a p.Leu424Cys. Two bioinformatics softwares all were indicated the mutation had affected the function of the protein. The c.738G>A heterozygous nonsense variation and the c.1325delT heterozygous deletion variation are associated with decreased FXI levels in this family, which is the first reported in the world. Severe acquired platelet dysfunction because of primary myelofibrosis with full functional and morphological recovery after allogeneic hematopoietic cell transplantation Primary myelofibrosis (PMF) is a clonal hematopoietic stem cell disorder characterized by fibrosis of the marrow cavity, marked megakaryocyte atypia and progressive cytopenias. Although thrombosis predominates, bleeding is the primary manifestation in up to 20% of patients and may be life-threatening. In this report, we document restoration of megakaryocyte and platelet structure and function in PMF after allogeneic hematopoietic cell transplantation (HCT). A 59-year-old man presented with recurrent episodes of postoperative bleeding preceding a diagnosis of primary myelofibrosis (PMF). Platelet aggregation and secretion studies showed abnormal responses to all agonists tested (epinephrine, ADP, arachidonic acid, U46619, collagen, ristocetin) despite the presence of thrombocytosis. After an allogeneic HCT, platelet morphology and function studies were all normal. The pathophysiology of platelet dysfunction in myeloid neoplasia is not well understood but, as highlighted in our report, restoration of platelet function by HCT supports a clonal process involving an early hematopoietic progenitor cell. Bernard–Soulier syndrome associated with 22q11.2 deletion and clinical features of DiGeorge/velocardiofacial syndrome Bernard–Soulier syndrome (BSS) is a rare autosomal recessive bleeding disorder caused by a defective function of glycoprotein (GP) Ib-V-IX complex. Among the genes encoding the 4 receptor subunits (GPIbα, GPIbβ, GPV and GPIX), the GPIbβ gene is located on chromosomes 22q11.2. We report a case of a girl with BSS associated with clinical features of 22q11.2 deletion syndrome (22q11.2DS) with phenotypic spectrum of DiGeorge syndrome/velocardiofacial syndrome. She has a history of life-long bleeding tendency, tetralogy of Fallot, hypothyroidism, mild facial dysmorphic signs and macrothrombocytopenia. The BBS and 22q11.2DS association could be explained by the fact that the constitutional hemizygosity of 22q11.2 may unmask an autosomal recessive disorder caused by alterations of the nondeleted GPIbβ allele. We suggest that all patients with 22q11.2DS and bleeding manifestations should be always tested for BSS. Argatroban to achieve therapeutic anticoagulation in two patients with acute thrombosis and heparin resistance We present two cases where argatroban was successfully used in patients with acute thrombosis requiring anticoagulant treatment where heparin resistance with unfractionated heparin had been encountered. The first case was a woman with abdominal arterial thrombosis, of unknown cause, treated with therapeutic low molecular weight heparin that developed pulmonary embolism despite therapeutic anticoagulation (and had evidence of heparin resistance on anti-Xa monitoring). The second patient had provoked abdominal arterial thrombosis from sepsis and could not attain therapeutic anticoagulation with intravenous unfractionated heparin. In both cases therapeutic anticoagulation was achieved with the use of argatroban, as a temporizing measure to treat the acute thrombotic event. Conventionally, argatroban has been described for use in heparin-induced thrombocytopenia. The use of argatroban is briefly discussed, especially in the context of heparin resistance where anticoagulation can be challenging. Further research using argatroban in heparin resistant patients could be justified.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

08:27

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com, Telephone consultation 11855 int 1193,

Die Fußballerhüfte Zusammenfassung Während Beschwerden und Verletzungen an Knie- und Sprunggelenk im...Die FußballerhüfteZusammenfassungWährend Beschwerden und Verletzungen an Knie- und Sprunggelenk im Fußball sehr präsent sind, wird dem Hüftgelenk bisher eine nur sehr geringe Aufmerksamkeit geschenkt. Beschwerden in diesem Bereich werden häufig auf pathologische Veränderungen in der Leistenregion zurückgeführt. Intraartikuläre Differenzialdiagnosen werden hingegen häufig nicht in Betracht gezogen....