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Assessing Coarse-Grained MARTINI Force-Fields pertaining to Catching your Ripple Phase involving Lipid Walls.
© 2020 Société Française de Pharmacologie et de Thérapeutique.Vitamin C (VitC) is an essential vitamin that needs to be provided through exogenous sources. It is a potent anti-oxidant, and an essential cofactor for many enzymes including a group of enzymes that modulate epigenetic regulation of gene expression. Moreover, VitC has a significant influence on T-cell differentiation, and can directly interfere with T-cell signaling. Conventional CD4 and CD8 T cells express the αβ TCR and recognize peptide antigens in the context of MHC presentation. The numerically small population of γδ T cells recognizes antigens in an MHC-independent manner. γδ T cells kill a broad variety of malignant cells, and because of their unique features, are interesting candidates for cancer immunotherapy. In this review, we summarize what is known about the influence of VitC on T-cell activation and differentiation with a special focus on γδ T cells. The known mechanisms of action of VitC on αβ T cells are discussed and extrapolated to the effects observed on γδ T-cell activation and differentiation. Overall, VitC enhances proliferation and effector functions of γδ T cells and thus may help to increase the efficacy of γδ T cells applied as cancer immunotherapy in adoptive cell transfer. ©2020 Society for Leukocyte Biology.AIM Tablets can be manipulated in several ways to obtain a fraction as the dose-a practice frequently seen in paediatric care due to lack of suitable formulations. Splitting tablets prior to fragment dispersion in a small volume of liquid is one such method. The objective of this study was to investigate the accuracy and precision of this method. METHODS Four different types of aspirin tablets (two dispersible, one conventional and one chewing) were split with a tablet splitter into half and quarter fragments. The fragments were dispersed in a medicine measure or an oral syringe. The amount recovered was determined by UHPLC analysis. RESULTS The largest quarter fragments ranged from 26.7% to 31.5% of the full tablet weight. Dispersing the fragment in an oral syringe, the amount recovered was greater than 90.8% of the fragment manipulated for all four tablet types, when rinsing was performed. Dispersing the fragment in a medicine measure, the amounts recovered spanned from 32.9% for the conventional tablets to 98.7% for one of the dispersible tablets. CONCLUSION Dispersion of half or quarter tablets directly in an oral syringe, but not a medicine measure, could give satisfactory recovery from fragments of all the investigated aspirin tablets. © 2020 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.Nowadays there are approximately 80 Anglophone journals that deal primarily with disaster risk reduction (DRR) and allied fields. This large array signals a sustained, if uneven, growth in DRR scholarship but also competition between the offerings of different publishers and institutions. The purpose of this article is first to summarise the development of academic publishing on DRR from its early beginnings to the present day. The paper then evaluates the current state of publishing in this field and discusses possible future trends. Next, it identifies some possible opportunities, challenges, expectations, and commitments for journal editors both within DRR and academia more broadly, including those that refer to changes in the use of terminology, the relentless increase in the number of papers submitted, the expansion and dangers of predatory journals, different peer review models, open access versus paywalls, citations and bibliography metrics, academic social networks, and copyright and distribution issues. This article is protected by copyright. All rights reserved.OBJECTIVES The present study explored how challenge and threat responses to stress relate to performance, anxiety, confidence, team identity and team characteristics (time spent in training and postgraduate experience) in a medical simulation-based team competition. METHODS The study was conducted during a national simulation-based training event for residents, the SIMCUP Italia 2018. The SIMCUP is a simulation competition in which teams of four compete in simulated medical emergency scenarios. Cross-sectional data were collected prior to the 3 days of the competition. Subjects included 95 participants on 24 teams. Before the competition on each day, participants completed brief self-report measures that assessed demands and resources (which underpin challenge and threat responses to stress), cognitive and somatic anxiety, self-confidence and team identification. Participants also reported time (hours) spent practising as a team and years of postgraduate experience. Phlorizin clinical trial A team of referees judged each scenario forsources, and the interaction between the two. Higher levels of resources and lower demands were associated with better performance. © 2020 John Wiley & Sons Ltd and The Association for the Study of Medical Education.BACKGROUND Autosomal recessive mutations in the glucocerebrosidase gene, Beta-glucocerebrosidase 1 (GBA1), cause the lysosomal storage disorder Gaucher's disease. Heterozygous carriers of most GBA1 mutations have dramatically increased Parkinson's disease (PD) risk, but the mechanisms and cells affected remain unknown. Glucocerebrosidase expression is relatively enriched in astrocytes, yet the impact of its mutation in these cells has not yet been addressed. OBJECTIVES Emerging data supporting non-cell-autonomous mechanisms driving PD pathogenesis inspired the first characterization of GBA1-mutant astrocytes. In addition, we asked whether LRRK2, likewise linked to PD and enriched in astrocytes, intersected with GBA1 phenotypes. METHODS Using heterozygous and homozygous GBA1 D409V knockin mouse astrocytes, we conducted rigorous biochemical and image-based analyses of lysosomal function and morphology. We also examined basal and evoked cytokine response at the transcriptional and secretory levels. RESULTS The D409V knockin astrocytes manifested broad deficits in lysosomal morphology and function, as expected. This, however, is the first study to show dramatic defects in basal and TLR4-dependent cytokine production. Albeit to different extents, both the lysosomal dysfunction and inflammatory responses were normalized by inhibition of LRRK2 kinase activity, suggesting functional intracellular crosstalk between glucocerebrosidase and LRRK2 activities in astrocytes. CONCLUSIONS These data demonstrate novel pathologic effects of a GBA1 mutation on inflammatory responses in astrocytes, indicating the likelihood of broader immunologic changes in GBA-PD patients. Our findings support the involvement of non-cell-autonomous mechanisms contributing to the pathogenesis of GBA1-linked PD and identify new opportunities to correct these changes with pharmacological intervention. © 2020 International Parkinson and Movement Disorder Society. © 2020 International Parkinson and Movement Disorder Society.
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