Inhibition of influenza A virus replication by a marine derived quinolone alkaloid targeting virus nucleoprotein

alexandrossfakianakis shared this article with you from Inoreader Inhibition of influenza A virus replication by a marine derived quinolone alkaloid targeting virus nucleoprotein via Journal of Medical Virology Abstract Owing to the emergence of drug resistance and high morbidity and mortality, the need for novel anti-influenza A virus (IAV) drugs with divergent targets is highly sought after. Herein, a novel quinolone alkaloid (QLA) derived from marine fungus was discovered with broad-spectrum anti-IAV activities with low toxicity. Distinct from current anti-IAV drugs, QLA may block virus replication and viral RNA (vRNA) export from the nucleus by targeting virus nucleoprotein (NP). QLA can block the binding of chromosome region maintenance 1 (CRM1) to nuclear export signal 3 (NES3) of NP to inhibit the nuclear export of NP and vRNP. QLA may also affect vRNP assembly by interfering with the binding of NP to RNA rather than NP oligomerization. Arg305 and Phe488-Gly490 may be required for the interaction between QLA and NP, and the binding pocket around these amino acids may be a promising target for anti-IAV drugs. Importantly, oral administration of QLA can protect the mice against IAV-induced d eath and weight loss, superior to the effects of the clinical drug oseltamivir. In summary, the marine derived compound QLA has the potential to be developed into a novel anti-IAV agent targeting virus NP protein in the future. This article is protected by copyright. All rights reserved. View on Web

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Osseointegration and Bone Resorption of Scapula Tip Free Flaps in Mandibular Reconstruction

alexandrossfakianakis shared this article with you from Inoreader Osseointegration and Bone Resorption of Scapula Tip Free Flaps in Mandibular Reconstruction via The Laryngoscope Few studies have shown significant bone resorption over time in scapula free flaps for mandibulectomy defects. Our series show high rates of osseous union and limited bone resorption that is equivalent to other vascularized osseous flaps. Objectives Bone resorption of more conventional vascularized bone grafts have been well described showing minimal resorption over time. Few studies have evaluated osseous union and bone resorption in scapula tip free flaps (STFF) in the reconstruction of mandibulectomy defects. We aimed to describe our series on STFF with respect to osseous union and bone resorption over time. Methods Retrospective chart review of patients receiving STFF from January 2014–January 2017 (n = 25). A neuroradiologist analyzed follow-up CT scans to assess (1) STFF complete, partial, or no osseous union with native mandible and (2) STFF volume change over time in a subset with multiple follow-up scans (n = 18). Results Twenty-three of 25 patients (92%) showed complete or partial STFF osseous union with native mandible either distally or proximally. STFF volume change ranged from +4.8 to −54% (median −0.5%) over median follow-up interval of 23 months. History of chemoradiation therapy, bisphophonate use, sex, age, or smoking history did not correlate with bone resorption. Conclusions STFFs shows high rates of osseous union and limited bone resorption that is equivalent to, or less than, vascularized fibular and iliac crest flaps. Clinically, this translates into both optimal healing and functional and cosmetic outcomes, especially in the setting of prior therapies. Level of Evidence 4 Laryngoscope, 2023 View on Web

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The Efficacy of Human Papillomavirus Vaccination as an Adjuvant Therapy in Recurrent Respiratory Papillomatosis

alexandrossfakianakis shared this article with you from Inoreader The Efficacy of Human Papillomavirus Vaccination as an Adjuvant Therapy in Recurrent Respiratory Papillomatosis via The Laryngoscope A systematic review and meta-analysis was done to characterize the efficacy of human papillomavirus (HPV) vaccination as an adjuvant therapy in recurrent respiratory papillomatosis (RRP). The addition of HPV vaccination was associated with an increase in time between surgeries, and reduced the number of surgical procedures required for patients with RRP. HPV vaccination may be a beneficial adjuvant treatment for RRP. Objective To characterize the efficacy of human papillomavirus (HPV) vaccination as an adjuvant therapy in recurrent respiratory papillomatosis (RRP). Data Sources PubMed, Embase, Cochrane, Google Scholar, ClinicalTrials.gov, and Web of Science databases were queried for articles published before April 2021. Review Methods All retrieved studies (n = 870) were independently analyzed by two reviewers according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement using predefined inclusion and exclusion criteria. 13 studies met inclusion criteria. A random-effects meta-analysis was performed to study intersurgical interval (ISI) and number of surgical procedures per year before and after vaccination. Results The systematic review included 13 studies, comprising 243 patients. All studies utilized the Gardasil® quadrivalent vaccine, and one study (Yiu et al. 2019) utilized both the quadrivalent and Gardasil® 9-valent vaccines. Our meta-analysis included 62 patients with ISI data across 4 studies, and 111 patients with data on the number of surgical procedures per month across 7 studies. The mean number of surgical procedures decreased by 4.43 per year after vaccination (95% CI, −7.48 to −1.37). Mean ISI increased after vaccination, with a mean difference of 15.73 months (95% CI, 1.46–29.99). Two studies reported on HPV sero-conversion, with HPV seropositivity of 100% prior to vaccination and 25.93% after vaccination. Conclusion The addition of HPV vaccination was associated with an increase in time between surgeries and reduction in the number of surgical procedures required. HPV vaccination may be a beneficial adjuvant treatment for RRP. Level of Evidence N/A Laryngoscope, 2023 View on Web

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Carolyn's Window Approach to Unilateral Frontal Sinus Surgery

alexandrossfakianakis shared this article with you from Inoreader Carolyn's Window Approach to Unilateral Frontal Sinus Surgery via The Laryngoscope Carolyn's window approach aims to remove the limitation created by the anterior-posterior depth to make a Draft 2a frontal sinusotomy easier for the surgeon. The approach is a 0° endoscope technique and provides an excellent view of the frontal sinus and recess. Objectives Due to the complexity and variety of the frontal recess and sinus anatomy, traditional Draf 2a frontal sinus surgery is challenging. The thickness of the nasofrontal beak and anterior–posterior dimensions of the frontal recess contribute to this complexity. Carolyn's window technique eliminates the limitation of anterior–posterior depth to facilitate a Draf 2a frontal sinusotomy. The approach is a 0° endoscope technique and provides an excellent view of the frontal sinus and recess. We describe Carolyn's window approach to frontal sinus surgery and the perioperative outcomes. Methods Consecutive adult patients in whom Carolyn's window technique was applied for frontal sinus dissection as part of the endoscopic management of both inflammatory and neoplastic disease were assessed. The primary outcome was frontal sinus patency. Secondary outcomes were surgical morbidity, defined as early (<90 days) or late (>90 days). Results Forty-five patients (49.1 ± 17.9 years, 48.9% Female) were assessed. All patients had successful frontal sinus patency (100% [95CI: 92.1%–100%]). Morbidities were adhesion (4.8%), crusting (2.4%), pain (1.2%), and bleeding (1.2%) in the early postoperative period. There were no other morbidities in the early and late postoperative periods. Conclusion Carolyn's window approach to frontal sinusotomy is a technique that evolves from previously described approaches. Successful frontal sinus patency with very low morbidities is achieved while still working with a 0° endoscope. The "axillectomy" performed simplifies frontal recess surgery by removing the anteroposterior diameter limitation and the dexterity required in angled endoscopy and instrumentation. The inferior-based lateral wall mucosal flap and free mucosal grafting expedite the mucosal healing process. Laryngoscope, 2023 View on Web

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Practitioner Review: It's time to bridge the gap – understanding the unmet needs of consumers with attention‐deficit/hyperactivity disorder – a systematic review and recommendations

alexandrossfakianakis shared this article with you from Inoreader Practitioner Review: It's time to bridge the gap – understanding the unmet needs of consumers with attention‐deficit/hyperactivity disorder – a systematic review and recommendations via Journal of Child Psychology and Psychiatry Objective Understanding the unmet needs of healthcare consumers with attention-deficit/hyperactivity disorder (ADHD) (individuals with ADHD and their caregivers) provides critical insight into gaps in services, education and research that require focus and funding to improve outcomes. This review examines the unmet needs of ADHD consumers from a consumer perspective. Methods A standardised search protocol identified peer-reviewed studies published between December 2011 and December 2021 focusing on consumer-identified needs relating to ADHD clinical care or research priorities. Results 1,624 articles were screened with 23 studies that reviewed examining the needs of ADHD consumers from Europe, the U.K., Hong Kong, Iran, Australia, the U.S.A. and Canada. Consumer-identified needs related to: treatment that goes beyond medication (12 studies); improved ADHD-related education/training (17 studies); improved access to clinical services, carer support and financial assistance (14 studies); school accommodations/support (6 studies); and ongoing treatment efficacy research (1 study). Conclusion ADHD consumers have substantial unmet needs in clinical, psychosocial and research contexts. Recommendations to address these needs include: improving access to and quality of multimodal care provision; incorporating recovery principles into care provision; fostering ADHD health literacy; and increasing consumer participation in research, service development and ADHD-related training/education. View on Web

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Role of Angiotensin Receptor Blockers in the context of Alzheimer’s Disease

alexandrossfakianakis shared this article with you from Inoreader Role of Angiotensin Receptor Blockers in the context of Alzheimer's Disease via Fundamental & Clinical Pharmacology Abstract As the world's population ages, the prevalence of age-related neurological disorders such as Alzheimer's disease (AD) is increasing. There is currently no treatment for Alzheimer's disease, and the few approved medications have a low success rate in lowering symptoms. As a result, several attempts are underway worldwide to identify new targets for the therapy of Alzheimer's disease. In pre-clinical studies of Alzheimer's disease, it was recently found that inhibition of angiotensin-converting enzyme (ACE) and blocking of the angiotensin II receptors reduce symptoms of neurodegeneration, Aβ plaque development, and tau hyperphosphorylation. Angiotensin II type I (AT1) blockers, such as telmisartan, candesartan, valsartan, and others, have a wide safety margin and are commonly used to treat hypertension. Renal and cardiovascular failure are reduced due to their vascular protective actions. Inhibition of AT1 receptors in the brain has a neuroprotective impact in humans, reducing the risk of stroke, increasing cognition, and slowing the progression of Alzheimer's disease. The review focuses on the mechanisms via which AT1 blockers may act beneficially in Alzheimer's disease. Although their effect is evident in pre-clinical studies, clinical trials, on the other hand, are in short supply to validate the strategy. More dose-response experiments with possible AT1 blockers and brain-targeted administration will be needed in the future. View on Web

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Comparative effectiveness of different primary vaccination courses on mRNA-based booster vaccines against SARs-COV-2 infections: a time-varying cohort analysis using trial emulation in the Virus Watch community cohort

alexandrossfakianakis shared this article with you from Inoreader Comparative effectiveness of different primary vaccination courses on mRNA-based booster vaccines against SARs-COV-2 infections: a time-varying cohort analysis using trial emulation in the Virus Watch community cohort via International Journal of Epidemiology - Advance Access Abstract Background The Omicron B.1.1.529 variant increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in doubly vaccinated individuals, particularly in the Oxford–AstraZeneca COVID-19 vaccine (ChAdOx1) recipients. To tackle infections, the UK's booster vaccination programmes used messenger ribonucleic acid (mRNA) vaccines irrespective of an individual's primary course vaccine type, and prioritized the clinically vulnerable. These mRNA vaccines included the Pfizer–BioNTech COVID-19 vaccine (BNT162b2) the Moderna COVID-19 vaccine (mRNA-1273). There is limited understanding of the effectiveness of different primary vaccination courses on mRNA booster vaccines against SARs-COV-2 infections and how time-varying confounders affect these evaluations. Methods Trial emulation was applied to a prospective community observational cohort in England and Wales to reduce time-varying confounding-by-indication driv en by prioritizing vaccination based upon age, vulnerability and exposure. Trial emulation was conducted by meta-analysing eight adult cohort results whose booster vaccinations were staggered between 16 September 2021 and 05 January 2022 and followed until 23 January 2022. Time from booster vaccination until SARS-CoV-2 infection, loss of follow-up or end of study was modelled using Cox proportional hazard models and adjusted for age, sex, minority ethnic status, clinically vulnerability and deprivation. Results A total of 19 159 participants were analysed, with 11 709 ChAdOx1 primary courses and 7450 BNT162b2 primary courses. Median age, clinical vulnerability status and infection rates fluctuate through time. In mRNA-boosted adults, 7.4% (n = 863) of boosted adults with a ChAdOx1 primary course experienced a SARS-CoV-2 infection compared with 7.7% (n = 571) of those who had BNT162b2 as a primary course. The pooled adjusted hazard ratio (aHR) was 1.01 with a 95% confidence interval (CI) of: 0.90 to 1.13. Conclusion After an mRNA booster dose, we found no difference in protection comparing those with a primary course of BNT162b2 with those with a ChAdOx1 primary course. This contrasts with pre-booster findings where previous research shows greater effectiveness of BNT162b2 than ChAdOx1 in preventing infection. View on Web

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Prenatal exposure to per- and polyfluoroalkyl substances and childhood autism-related outcomes

alexandrossfakianakis shared this article with you from Inoreader Prenatal exposure to per- and polyfluoroalkyl substances and childhood autism-related outcomes via Epidemiology - Published Ahead-of-Print Background: Epidemiologic evidence linking prenatal exposure to per- and polyfluoroalkyl substances (PFAS) with altered neurodevelopment is inconclusive, and few large studies have focused on autism-related outcomes. We investigated whether blood concentrations of PFAS in pregnancy are associated with child autism-related outcomes. Methods: We included ten cohorts from the National Institutes of Health (NIH)-funded Environmental influences on Child Health Outcomes (ECHO) Program (n=1429). We measured 14 PFAS analytes in maternal blood collected during pregnancy; eight analytes met detection criteria for analysis. We assessed quantitative autism-related traits in children via parent report on the Social Responsiveness Scale (SRS). In multivariable linear models, we examined relationships of each PFAS (natural log-transformed) with SRS scores. We further modeled PFAS as a complex mixture using Bayesian methods and examined modification of these relationships by child sex. Results: Most PFAS in maternal blood were not associated with child SRS T-scores. Perfluorononanoic acid (PFNA) showed the strongest and most consistent association: each 1-unit increase in ln-transformed PFNA was associated with greater autism-related traits (adj-β [95% CI]=1.5 [-0.1, 3.0]). The summed mixture, which included six PFAS detected in >70% of participants, was not associated with SRS T-scores (adj-β [95% highest posterior density interval]=0.7 [-1.4, 3.0]). We did not observe consistent evidence of sex differences. Discussion: Prenatal blood concentrations of PFNA may be associated with modest increases in child autism-related traits. Future work should continue to examine the relationship between exposures to both legacy and emerging PFAS and additional dimensional, quantitative measures of childhood autism-related outcomes. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved. View on Web

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Douching and genital talc use: Patterns of use and reliability of self-reported exposure

alexandrossfakianakis shared this article with you from Inoreader Douching and genital talc use: Patterns of use and reliability of self-reported exposure via Epidemiology - Published Ahead-of-Print Background: Feminine hygiene products contain chemicals that may be harmful to human health. Observational studies of the long-term health effects of such products largely rely on self-reported, recalled exposure. We sought to capture patterns of use over the life-course and evaluate the reliability of self-reported data. Methods: We collected retrospective data on douching and genital talc use in the US-based Sister Study at two time points and evaluated the consistency of reporting. At enrollment (2003-09), participants were asked to report use in the last year and during ages 10-13. On a follow-up questionnaire (2017-19), participants were asked about their use of douche or genital talc over their lifetimes. Results: Among 36,202 women who completed both questionnaires, 14% initially reported ever douching and 27% initially reported ever using genital talc. On the follow-up questionnaire, 51% of participants reported ever douching and 32% reported ever using genital talc. Comparisons across the two questionnaires for use in the year prior to enrollment showed good consistency, with 90% providing the same responses about douching and 87% providing the same responses about genital talc use. Reliability did not vary by cancer status, race and ethnicity, attained education, or age, though there was some evidence of recall bias for genital talc use among ovarian cancer survivors. Conclusions: Classification of ever use of feminine hygiene products may be recalled with good consistency, but agreement was lower for specific time periods and trends may vary by subgroup. These potential differences warrant careful consideration in future studies. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved. View on Web

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Cardio SEM: A Novel Approach for a Traffic Light System for Heart Failure Warning Signs

alexandrossfakianakis shared this article with you from Inoreader Cardio SEM: A Novel Approach for a Traffic Light System for Heart Failure Warning Signs via Computers Informatics Nursing - Published Ahead-of-Print Existing literature on the follow-up of heart failure patients with warning signs shows that it is necessary to increase patients' knowledge and of seeking help in a timely manner. This suggests an opportunity to implement strategies that integrate technology to visualize the risk of decompensation. This article studies the acceptance of Cardio Sem, a traffic light system mobile application for patients with heart failure. A descriptive, observational pilot study was performed with 23 outpatients belonging to a heart failure program. For 4 weeks, patients used Cardio Sem, which allows visualizing the risk of decompensati on through a series of questions that patients must answer daily and provides guidance for managing signs and symptoms of decompensation. A technology acceptance questionnaire was applied to all patients, resulting in acceptance of the application, especially in the dimensions that emphasized perceived usefulness (100%), social influence (100%), and behavioral intent (99.8%). Cardio Sem is useful for early detection of symptoms that allow for early response to complications. Acceptance of the application by patients and its ease of use present the possibility to implement it as a complementary tool to promote self-care and effective management of symptoms. View on Web

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