A role for primary cilia in coral calcification?

xlomafota.13 shared this article with you from Inoreader A role for primary cilia in coral calcification? Via Latest Results for Cell and Tissue Research Abstract Cilia are evolutionarily conserved organelles that extend from the surface of cells and are found in diverse organisms from protozoans to multicellular organisms. Motile cilia play various biological functions by their beating motion, including mixing fluids and transporting food particles. Non-motile cilia act as sensors that signal cells about their microenvironment. In corals, cilia have been described in some of the cell layers but never in the calcifying epithelium, which is responsible for skeleton formation. In the present study, we used scanning electron microscopy and immunolabelling to investigate the cellular ciliature of the different tissue layers of the coral Stylophora pistillata, with a focus on the calcifying calicoblastic ectoderm. We show that the cilium of the calcifying cells is different from the cilium of the other cell layers. It is much shorter, and more importantly, its base is structurally distinct from the base observed in cil ia of the other tissue layers. Based on these structural observations, we conclude that the cilium of the calcifying cells is a primary cilium. From what is known in other organisms, primary cilia are sensors that signal cells about their microenvironment. We discuss the implications of the presence of a primary cilium in the calcifying epithelium for our understanding of the cellular physiology driving coral calcification and its environmental sensitivity. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Extracranial dose and the risk of radiation-induced malignancy after intracranial stereotactic radiosurgery: is it time to establish a therapeutic reference level?

xlomafota.13 shared this article with you from Inoreader Extracranial dose and the risk of radiation-induced malignancy after intracranial stereotactic radiosurgery: is it time to establish a therapeutic reference level? Via Latest Results for Acta Neurochirurgica Abstract Background To measure extracranial doses from Gamma Knife Perfexion (GKP) intracranial stereotactic radiosurgery (SRS) and model the risk of malignancy after SRS for different treatment platforms. Methods Doses were measured for 20 patients undergoing SRS on a GKP at distances of 18, 43 and 75 cm from the target, corresponding to the approximate positions of the thyroid, breast and gonads respectively. A literature review was conducted to collect comparative data from other radiosurgery platforms. All data was used to calculate the dose to body organs. The National Cancer Institute (NCI) RadRAT calculator was used to estimate excess lifetime cancer risk from this exposure. Five different age groups covering childhood and younger adults were modelled for both sexes. Results Extracranial doses delivered during SRS with the GKP were a median 0.04%, 0.008% and 0.002% of prescription dose at 18 cm, 43 cm and 70 cm from the isocentre respectively. Comparison with the literature revealed that the extracranial dose was lowest from GKP, then linacs equipped with micro-multileaf collimators (mMLC), then linacs equipped with circular collimators (cones), and highest from Cyberknife (CK). Estimated lifetime risks of radiation-induced malignancy in the body for patients treated with SRS aged 5–45 years were 0.03–0.88%, 0.36–11%, 0.61–18% and 2.2–39% for GKP, mMLC, cones and CK respectively. Conclusions We have compared typical extracranial doses from different platforms and quantified the lifetime risk of radiation-induced malignancy. The risk varies with platform. This should be taken into account when treating children and young adults with SRS. The concept of a therapeutic reference level (TRL), similar to the diagnostic reference level (DRL) established in radiology, is proposed. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Impact of bridging thrombolysis on clinical outcome in stroke patients undergoing endovascular thrombectomy: a retrospective analysis of a regional stroke registry

xlomafota.13 shared this article with you from Inoreader Impact of bridging thrombolysis on clinical outcome in stroke patients undergoing endovascular thrombectomy: a retrospective analysis of a regional stroke registry Via Latest Results for Neuroradiology Abstract Purpose It is unclear whether stroke patients undergoing endovascular thrombectomy (EVT) should receive bridging intravenous thrombolysis (IVT), if eligible. This study aims at analyzing the impact of bridging IVT on short-term clinical outcome. Methods In a prospective regional stroke registry, all stroke patients with premorbid modified Rankin Scale (mRS) score of 0–2 who were admitted within 4.5 h after onset and treated with EVT were analyzed retrospectively. Patients receiving "IVT prior to EVT" (IVEVT) were compared to those undergoing "EVT only" regarding the ratio of good outcome, discharge mRS, mRS shift, hospital mortality, and occurrence of symptomatic intracranial hemorrhage. Results In total, 2022 patients were included, 816 patients (40.4%) achieved good clinical outcome; 1293 patients (63.9%) received bridging IVT. There was no significant difference between both groups regarding the ratio of good outcome (IVEVT 41.4% vs. EVT 38.5%, P = 0.231), discharge mRS (median, IVEVT 3 vs. EVT 3, P = 0.178), mRS shift (median, IVEVT 3 vs. EVT 3, P = 0.960), and hospital mortality (IVEVT 19.3% vs. EVT 19.5%, P = 0.984). Bridging IVT was not a predictor of outcome (adjusted OR 1.00, 95% CI 0.79–1.26, P = 0.979). However, it was an independent predictor of symptomatic intracranial hemorrhage (adjusted OR 1.79, 95% CI 1.21–2.72, P = 0.005). Conclusions The results of the present study suggest that bridging IVT does not seem to improve short-term clinical outcome of patients undergoing EVT. Nonetheless, there might be a subgroup of patients that benefits from IVT. This needs to be addressed in randomized controlled trials. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Feasibility and possible value of quantitative semi-automated diffusion weighted imaging volumetry of neuroblastic tumors

xlomafota.13 shared this article with you from Inoreader Feasibility and possible value of quantitative semi-automated diffusion weighted imaging volumetry of neuroblastic tumors Via Latest Results for Cancer Imaging Abstract Background To assess the feasibility and possible value of semi-automated diffusion weighted imaging (DWI) volumetry of whole neuroblastic tumors with apparent diffusion coefficient (ADC) map evaluation after neoadjuvant chemotherapy. Methods Pediatric patients who underwent surgical resection of neuroblastic tumors at our institution from 2013 to 2019 and who received a preoperative MRI scan with DWI after chemotherapy were included. Tumor volume was assessed with a semi-automated approach in DWI using a dedicated software prototype. Quantitative ADC values were calculated automatically of the total tumor volume after manual exclusion of necrosis. Manual segmentation in T1 weighted and T2 weighted sequences was used as reference standard for tumor volume comparison. The Student's t test was used for parametric data while the Wilcoxon rank sum test and the Kruskal-Wallis test were applied for non-parametric data. Results Twenty seven patients with 28 lesions (neuroblastoma (NB): n = 19, ganglioneuroblastoma (GNB): n = 7, ganglioneuroma (GN): n = 2) could be evaluated. Mean patient age was 4.5 ± 3.2 years. Median volume of standard volumetry (T1w or T2w) was 50.2 ml (interquartile range (IQR): 91.9 ml) vs. 45.1 ml (IQR: 98.4 ml) of DWI (p = 0.145). Mean ADC values (× 10− 6 mm2/s) of the total tumor volume (without necrosis) were 1187 ± 301 in NB vs. 1552 ± 114 in GNB/GN (p = 0.037). The 5th percentile of ADC values of NB (614 ± 275) and GNB/GN (1053 ± 362) provided the most significant difference (p = 0.007) with an area under the curve of 0.848 (p < 0.001). Conclusions Quantitative semi-automated DWI volumetry is feasible in neuroblastic tumors with integrated analysis of tissue characteristics by providing automatically calculated ADC values of the whole tumor as well as an ADC heatmap. The 5th percentile of the ADC values of the whole tumor volume proved to be the most significant parameter for differentiation of the histopathological subtypes in our patient cohort and further investigation seems to be worthwhile. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Adsorption of Methyl Blue onto Activated Carbon Derived from Red Oak ( Quercus rubra ) Acorns: a 2 6 Factorial Design and Analysis

xlomafota.13 shared this article with you from Inoreader Adsorption of Methyl Blue onto Activated Carbon Derived from Red Oak ( Quercus rubra ) Acorns: a 2 6 Factorial Design and Analysis Via Latest Results for Water, Air, & Soil Pollution Abstract In this study, red oak (Quercus rubra) acorns were used as precursor for preparing activated carbon by thermal activation. Red oak activated carbon (RAC) was evaluated for the removal of methyl blue (MB), using batch adsorption experiments. SEM images taken before and after adsorption experiments showed difference of surface morphology. A 26 full factorial design approach was used to determine the main and interaction effect of independent factors on dye removal rate. The six independent factors used for this study were sorbent dosage, initial dye concentration, pH, temperature, mixing rate (rpm), and mixing time. The response of this factorial design was percentage of dye removal (R%) from an aqueous solution. All independent factors showed significant influence. Initial dye concentration and adsorbent dose exhibited largest negative and positive influence on removal rate, respectively. The factorial experiments also demonstrated significan t synergistic/ antagonistic interaction between all these factors. Optimum conditions for adsorption were adsorbent dosage = 0.25 g/50 ml, initial dye concentration = 10.0 mg L 1, pH = 10, temperature = 45 °C, mixing rate = 175 rpm, and mixing time = 2.0 h. Under these conditions, response, dye removal rate R, was maximized, with a value of 97.18%. The findings of this study could be useful for industrial wastewater treatment systems. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effectiveness of low-level laser therapy on recovery from neurosensory disturbance after sagittal split ramus osteotomy: a systematic review and meta-analysis

xlomafota.13 shared this article with you from Inoreader Effectiveness of low-level laser therapy on recovery from neurosensory disturbance after sagittal split ramus osteotomy: a systematic review and meta-analysis Via Latest Results for Maxillofacial Plastic and Reconstructive Surgery Abstract Background Orthognathic surgery such as bilateral sagittal split ramus osteotomy (BSSRO) for the treatment of mandibular deformities is one of the most common procedures in maxillofacial operations that may lead to neurosensory disturbance. In this study, we aimed to evaluate the effectiveness of low-level laser therapy (LLLT) on augmenting recovery of neurosensory disturbance of inferior alveolar nerve (IAN) in patients who underwent BSSRO surgery. Methods A comprehensive literature search was conducted by two independent authors in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Embase, and Google Scholar electronic databases. Besides, a manual search of all textbooks and relevant articles were conducted. Searches took place in August 2020 and were limited to published and peer-reviewed articles from 2000 to 2020. All analysis was performed using the comprehensive meta-analysis (CMA) and the STATA MP (version:16) software. The weighted mean difference (WMD) using the inverse variance method and the standard mean difference (SMD) was considered for continuous variables. Results Seventy-four papers were retrieved after removing duplicate studies and finally, eight studies were assessed for qualitative synthesis and five for meta-analysis. Totally, 94 patients were included in the meta-analysis. Based on the meta-analysis, it was shown that LLLT was not effective in a short interval (0 to 48 h) after surgery, but in a period of more than 1 month after surgery, the positive results of treatment can be observed strikingly. Also, LLLT side/group showed no significant difference in some aspects of neurosensory recovery such as thermal sensation compared to the placebo side/group. Conclusions The meta-analysis of randomized controlled trials revealed that LLLT generally improves IAN sensory disturbance caused by BSSRO. Further high-quality clinical trials with longer follow-up periods and larger sample sizes are recommended. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

An update on the pathogenesis of Hashimoto’s thyroiditis

xlomafota.13 shared this article with you from Inoreader An update on the pathogenesis of Hashimoto's thyroiditis Via Latest Results for Journal of Endocrinological Investigation Abstract It is 70 years since Noel Rose embarked on his pioneering studies that lead to the discovery of autoimmune thyroiditis and the elucidation of Hashimoto's thyroiditis. This short review to honour his passing focuses on the developments in our understanding of the causes and pathogenesis of HT over the last five years. Recent genetic studies have reported heritability estimates for HT and associated diseases for the first time, and emphasised the complexity of the genetic factors involved, including monogenic forms of HT. Environmental factors continue to be elucidated, especially as a side effect of drugs which modulate the immune system therapeutically. Regarding pathogenetic mechanisms, multiple cytokine networks have been identified which involve the thyroid cells in a circuit of escalating proinflammatory effects, such as the expression of inflammasome components, and an array of different defects in T regulatory cells may underlie the loss of self-tole rance to thyroid autoantigens. Finally, a number of studies have revealed fresh insights into disease associations with HT which may have both pathological and clinical significance, the most intriguing of which is a possible direct role of the autoimmune process itself in causing some of the persistent symptoms reported by a minority of patients with levothyroxine-treated HT. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The Roles of Insulin-Like Growth Factor Binding Protein Family in Development and Diseases

xlomafota.13 shared this article with you from Inoreader The Roles of Insulin-Like Growth Factor Binding Protein Family in Development and Diseases Via Latest Results for Advances in T... Abstract The insulin-like growth factor (IGF) system comprises ligands of IGF-I/II, IGF receptors (IGFR), IGF binding proteins (IGFBPs), and IGFBP hydrolases. The IGF system plays multiple roles during various disease development as IGFs are widely involved in cell proliferation and differentiation through regulating DNA transcription. Meanwhile, IGFBPs, which are mainly synthesized in the liver, can bind to IGFs and perform two different functions: either inhibition of IGFs by forming inactive compounds with IGF or enhancement of the function of IGFs by strengthening the IGF–IGFR interaction. Interestingly, IGFBPs may have wider functions through IGF-independent mechanisms. Studies have shown that IGFBPs play important roles in cardiovascular disease, tumor progression, fetal growth, and neuro-nutrition. In this review, we emphasize that different IGFBP family members have common or unique functions in numerous diseases; moreover, IGFBPs may serve as biomarkers for dis ease diagnosis and prediction. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Efficacy of Tofacitinib in the Treatment of Psoriatic Arthritis: A Systematic Review

xlomafota.13 shared this article with you from Inoreader Efficacy of Tofacitinib in the Treatment of Psoriatic Arthritis: A Systematic Review Via Latest Results for Advances in T... Abstract Introduction Therapeutic approaches for psoriatic arthritis (PsA) include non-pharmacologic therapies, symptomatic treatments, tumor necrosis factor inhibitors, interleukin inhibitors, cytotoxic T lymphocyte antigen 4 immunoglobulin, and Janus kinase inhibitors. This systematic review aimed to provide complete and up-to-date information on efficacy of tofacitinib in the treatment of PsA, giving special attention to non-skin manifestations (peripheral arthritis, axial disease, enthesitis, and dactylitis). Methods A search of studies published between January 2016 and June 2020 was carried out on PubMed and Google Scholar. Results The number of studies with tofacitinib in PsA is limited and most of them are post hoc analyses from OPAL Broaden and OPAL Beyond. Tofacitinib has been demonstrated to be efficacious for the treatment of all disease manifestations in PsA. Superior effectivity to placebo is achieved at the earliest time point evaluated, and maintained over time. Patients who switch from placebo to tofacitinib show the same improvements; however, the time to initial response is faster in patients who firstly receive tofacitinib, compared with those switching subsequently. Additional data suggest that tofacitinib may be also effective for the treatment of the axial domain. Conclusions Tofacitinib has been demonstrated to be efficacious for the treatment of peripheral and axial involvement, enthesitis, and dactylitis manifestation in PsA. Further prospective and long-term studies are required to corroborate and complete the present results. Similarly, real-world evidence is also necessary to complement the information obtained in clinical trials, and thereby to have a better overview of real efficacy and safety of the drug. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Time to Treatment Discontinuation in German Patients with Schizophrenia: Long-Acting Injectables versus Oral Antipsychotics

xlomafota.13 shared this article with you from Inoreader Time to Treatment Discontinuation in German Patients with Schizophrenia: Long-Acting Injectables versus Oral Antipsychotics Via Latest Results for Clinical Drug Investigation Abstract Background and Objective Long-acting injectable antipsychotics (LAIs) are associated with better treatment adherence and persistence than oral antipsychotics (OAPs) in patients with schizophrenia. However, real-world evidence assessing the impact of treatment with LAIs in Germany is limited. To fill this gap, we compared antipsychotic medication adherence and risk of treatment discontinuation (TD) among schizophrenia patients newly initiated on LAI or who switched their OAP regimen (overall cohort; OC). Methods Claims data of German schizophrenia patients who initiated LAIs or switched their OAP during 2012–2016 (index date) were retrospectively analyzed. Treatment switch was defined as add-on medication to existing prescription or terminating the existing prescription and initiating another OAP. Adherence and time to treatment discontinuation (TTD) were estimated. Determinants of treatment discontinuation were analyzed using two Cox regression models. Model 1 controlled for age, sex, and Charlson Comorbidity Index (CCI); model 2 also included insurance status, and medication, visit, and psychiatric inpatient stay costs. Sensitivity analysis on patients who terminated existing prescriptions and initiated new OAPs (complete switch cohort; CSC) was performed. Results In OC (n = 2650), LAI users had better adherence (35.4% vs. 11.6%), persistence (no 60-day gap; 40.7% vs. 19.8%), and longer TTD (median [95% confidence interval (CI)] 216 [193–249] vs. 50 [46–56] days) than OAP users. OAP usage (hazard ratio [HR] 1.89, 95% CI 1.73–2.06; p < 0.001) and greater CCI (HR 1.04, 95% CI 1.00–1.07; p = 0.023) were associated with greater risk of TD in model 1. Model 2 showed similar results. LAI users in CSC also had better adherence, persistence, and longer TTD. In CSC too, OAP usage and greater CCI were associated with greater risk of TD in model 1, but only CCI was significant in model 2. Higher pre-index psychiatric inpatient costs were associated with lower risk of TD (HR 0.99, 95% CI 0.98–1.00; p = 0.014). Limitations Inherent limitations of claims data and lack of control on OAP administration may have influenced the results. Conclusion This real-world study associates LAIs with better medication adherence and lower antipsychotic discontinuation risk than OAPs. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

First-in-Man Safety, Tolerability, and Pharmacokinetics of a Novel and Highly Selective Inhibitor of Matrix Metalloproteinase-12, FP-025: Results from Two Randomized Studies in Healthy Subjects

xlomafota.13 shared this article with you from Inoreader First-in-Man Safety, Tolerability, and Pharmacokinetics of a Novel and Highly Selective Inhibitor of Matrix Metalloproteinase-12, FP-025: Results from Two Randomized Studies in Healthy Subjects Via Latest Results for Clinical Drug Investigation Abstract Background and Objectives Matrix metalloproteinases (MMPs) are proteases with different biological and pathological activities, and many have been linked to several diseases. Targeting individual MMPs may offer a safer therapeutic potential for several diseases. We assessed the safety, tolerability, and pharmacokinetics of FP-025, a novel, highly selective oral matrix metalloproteinase-12 inhibitor, in healthy subjects. Methods Two randomized, double-blind, placebo-controlled studies were conducted. Study I was a first-in-man study, evaluating eight single ascending doses (SADs) (50–800 mg) in two formulations: i.e., neat FP-025 in capsule (API-in-Capsule) and in an amorphous solid dispersion (ASD-in-Capsule) formulation. In Study II, three multiple ascending doses (MADs) (100, 200, and 400 mg, twice daily) of FP-025 (ASD-in-Capsule) were administered for 8 days, including a food-effect evaluation. Results Ninety-six subjects were dosed. Both formulations were well tolerated with one adverse event (AE) reported in the 800 mg API-in-Capsule SAD group and seven AEs throughout the MAD groups. The exposure to FP-025 was low with the API-in-Capsule formulation; it increased dose-dependently with the ASD-in-Capsule formulation, with which exposure to FP-025 increased in a greater-than-dose-proportional manner at lower doses (≤ 100 mg) but less proportionally at higher doses. The elimination half-life (t1/2) was between 6 (Study I) and 8 h (Study II). Accumulation of FP-025 was approximately 1.7-fold in the MAD study. Food intake delayed the rate of absorption, but without effect in the extent of absorption or bioavailability. Conclusion FP-025 was well tolerated and showed a favorable pharmacokinetic profile following ASD-in-Capsule dosing. Efficacy studies in target patient populations, including asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis, are warranted. Trial registration number: www.clinicaltrials.gov: NCT02238834 (Study I); NCT03304964 (Study II). Trial registration date: Study I was registered on 12 September 2014 while study II was registered on 9 October 2017. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.