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  • Bernstein Bowers posted an update 15 days ago

    In conclusion, TRAN can be proposed as an effective drug to attenuate MTX-induced organ toxicity via modulation of apoptosis-induced tissue proliferation pathway. © 2020 Wiley Periodicals, Inc.Baloxavir marboxil is a novel endonuclease inhibitor licensed for treatment of otherwise healthy or high-risk individuals infected with influenza. Viruses with reduced baloxavir susceptibility due to amino acid substitutions at residue 38 of the PA have been detected in some individuals following treatment. Here, we describe a genotypic pyrosequencing method that can be used to rapidly screen circulating influenza A and B viruses for substitutions in the PA/I38 codon and to quantify mixed viral populations. This method is suitable for surveillance of baloxavir susceptibility and to analyse samples from hospitalised patients undergoing baloxavir treatment to aid in clinical decision making. © 2020 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.Typically, the morphologies of the self-assembled nanostructures from block copolymers are limited to spherical micelles, wormlike micelles and vesicles. Herein, we report a new generation of materials with unique shape and structures, cylindrical soft matter particles (tubisomes), obtained from the hierarchical self- assembly of cyclic peptide-bridged amphiphilic diblock copolymers. Additionally, the capacity of obtained photo-responsive tubisomes as potential drug carriers is evaluated. The supramolecular tubisomes described here paves an alternative way for fabricating polymeric tubular structures, and will expand the toolbox for the rational design of functional hierarchical nanostructures. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.We report a RhIII -catalyzed regio- and diastereoselective synthesis of δ-lactams from readily available acrylamide derivatives and unactivated alkenes. The reaction provides a rapid route to a diverse set of δ-lactams in good yield and stereoselectivity, which serve as useful building blocks for substituted piperidines. The regioselectivity of the reaction with unactivated terminal alkene is significantly improved by using Cpt ligand on the RhIII catalyst. TASIN-30 datasheet The synthetic utility of the reaction is demonstrated by the preparation of a potential drug candidate containing a trisubstituted piperidine moiety. Mechanistic studies show that the reversibility of the C-H activation depends on the choice of Cp ligand on the RhIII catalyst. The irreversible C-H activation is observed and becomes turnover-limiting with [Cpt RhCl2 ]2 as catalyst. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.INTRODUCTION The COPD Assessment Test (CAT) is utilised to evaluate the treatment outcome regarding the health status in idiopathic interstitial pneumonia (IIP). However, the ability of the CAT to evaluate the lung-specific quality of life in systemic sclerosis-associated interstitial lung disease (SSc-ILD) is not established. Therefore, we investigated whether CAT scores can be used to evaluate SSc-ILD as they are for IIP. METHODS A total of 150 patients with IIP or SSc-ILD who were evaluated by the CAT were retrospectively assigned to this study. Clinical data at the visit for the CAT were analysed. RESULTS The forced vital capacity and distance walked during the 6-minute walk test (6MWD) were significantly correlated with the CAT score for SSc-ILD and IIP, and the CAT scores were similarly distributed in SSc-ILD and IIP. The CAT score of SSc-ILD patients was negatively affected by pulmonary arterial hypertension, but not by corticosteroids, which affected it in IIP patients. CAT scores of patients with either disease receiving home oxygen therapy were poor. In multiple regression analysis, pulmonary arterial hypertension and 6MWD were independent predictors for the CAT score in patients with SSc-ILD, while corticosteroid administration was selected as an independent factor in patients with IIP. CONCLUSIONS Our study suggests that the CAT can be applied to evaluate the lung-specific quality of life in SSc-ILD similar to IIP regarding the pulmonary function, but it should be noted that pulmonary arterial hypertension in SSc-ILD influences the CAT score. © 2020 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.Dysregulation of lung endothelial barrier function may lead to lethal outcomes, as demonstrated in the case of the acute respiratory distress syndrome (ARDS). p53 participates in the regulation of the lung endothelial barrier, and it has been associated both in vivo and in vitro with protective effects against the LPS-induced hyperpermeability. Family members of the never in mitosis A-related kinases (NEKs) are crucial mediators of fundamental cellular processes, including mitosis, and have been shown to posttranslationally modify p53. Since such modifications affect p53 stability and activity, it is highly probable that NEK kinases are also regulators of lung endothelial permeability. Thus, they may serve as possible therapeutic targets for treatment of pathologies associated with endothelial barrier dysfunction. © 2020 International Union of Biochemistry and Molecular Biology.BACKGROUND Service user and carer perspectives on safety issues in mental health services are not well known and may be important in preventing and reducing harm. The development of the Yorkshire Contributory Factors Framework-Mental Health (YCFF-MH) provides a broad structure within which to explore these perspectives. OBJECTIVE To explore what service users of mental health services and their carers consider to be safety issues. DESIGN, SETTING AND PARTICIPANTS Qualitative interviews with 13 service users and 7 carers in the UK. Participants were asked about their experiences and perceptions of safety within mental health services. Perceived safety issues were identified using framework analysis, guided by the YCFF-MH. RESULTS Service users and carers identified a broad range of safety issues. These were categorized under ‘safety culture’ and included psychological concepts of safety and raising concerns; ‘social environment’ involved threatened violence and sexual abuse; ‘individual service user and staff factors’ dominated by not being listened to; ‘management of staff and staffing levels’ resulting in poor continuity of care; and ‘service process’ typified by difficulty accessing services during a crisis.

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