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Study primary outcomes include RAO and haematoma; secondary outcomes are compression time, patient discomfort, time to discharge and ease of use of the intervention technique by the healthcare staff. χ

test will be used to compare the categorical outcomes between two arms and student's t-test for continuous outcomes. A p value of <0.05 will be considered significant.

Ethical approval for the study has been obtained from the Institutional Review Board of Tabba Heart Institute number IORG0007863. Findings will be disseminated through seminars and scientific publications.

NCT04380883; Pre-results.

NCT04380883; Pre-results.

To develop and validate a prediction model for predicting in-hospital mortality in patients with acute pancreatitis (AP).

A retrospective observational cohort study based on a large multicentre critical care database.

All subject data were collected from the eICU Collaborative Research Database (eICU-CRD), which covers 200 859 intensive care unit admissions of 139 367 patients in 208 US hospitals between 2014 and 2015.

A total of 746 patients with AP were drawn from eICU-CRD. Due to loss to follow-up (four patients) or incomplete data (364 patients), 378 patients were enrolled in the primary cohort to establish a nomogram model and to conduct internal validation.

The outcome of the prediction model was in-hospital mortality. All risk factors found significant in the univariate analysis were considered for multivariate analysis to adjust for confounding factors. Then a nomogram model was established. The performance of the nomogram model was evaluated by the concordance index (C-index) and the calibrdily available data, exhibited high predictive value for predicting in-hospital mortality in AP.

C-reactive protein (CRP), a biomarker of infection, has been used widely in high-income settings to guide antibiotic treatment in patients presenting with respiratory illnesses in primary care. Recent trials in low- and middle-income countries showed that CRP testing could safely reduce antibiotic use in patients with non-severe acute respiratory infections (ARIs) and fever in primary care. The studies, however, were conducted in a research-oriented context, with research staff closely monitoring healthcare behaviour thus potentially influencing healthcare workers' prescribing practices. For policy-makers to consider wide-scale roll-out, a pragmatic implementation study of the impact of CRP point of care (POC) testing in routine care is needed.

A pragmatic, cluster-randomised controlled trial, with two study arms, consisting of 24 commune health centres (CHC) in the intervention arm (provision of CRP tests with additional healthcare worker guidance) and 24 facilities acting as controls (routine care). Comrence07/HDDD-NDTW/2019). Results from this study will be disseminated via meetings with stakeholders, conferences and publications in peer-reviewed journals. Authorship and reporting of this work will follow international guidelines.

NCT03855215; Pre-results.

NCT03855215; Pre-results.

Childhood and adolescence are crucial life stages for health trajectories and the development of health inequalities in later life. The relevance of schools for health and well-being of children and adolescents has long been recognised, and there is some research regarding the association of contextual and compositional characteristics of schools and classes with health, health behaviour and well-being in this population. Little is known about the role of meso-level characteristics in relation to health inequalities. The aim of this scoping review is to retrieve and synthesise evidence about the mediating or moderating role of compositional or contextual characteristics of schools for the association between students' socioeconomic position and health in primary and secondary education.

We will conduct a systematic search of electronic databases in PubMed/Medline, Web of Science and Education Resources Information Center. Studies must meet the following inclusion criteria (1) The population must be studenry data and only include secondary data derived from previously published studies. Therefore, ethical approval is not required. We intend to publish our findings in an international peer-reviewed journal and to present them at national and international conferences.

Transcranial direct current stimulation (tDCS) is a potentially novel strategy for cognitive enhancement in patients with disorders. We present a study protocol for a randomised controlled trial designed to evaluate the safety and efficacy of tDCS combined with cognitive tasks on cognition in such patients.

This is a two-arm, parallel-design, randomised, sham-controlled trial, in which participants and raters will be blinded at a single centre. Stratified randomisation will be conducted, and a randomisation sequence will be generated through the Electronic Data Capture system. Patients who met the Diagnostic and Statistical Manual of Mental Disorders-5 criteria for neurocognitive disorders will be recruited and randomised to receive either active (2 mA for 20 min) or sham (stimulation ramped up and down for 1 min) stimulation in 10 sessions over five consecutive days. A direct current will be transferred by a 35 cm

saline-soaked sponge electrode. An anode will be placed over the left dorsolateral prefroroved this study. The results of this study will be published in a scientific peer-reviewed journal.

Japan Registry of Clinical Trials jRCTs032180016.

Japan Registry of Clinical Trials jRCTs032180016.Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection.The initial activation step in the gating of ubiquitously expressed Orai1 calcium (Ca2+) ion channels represents the activation of the Ca2+-sensor protein STIM1 upon Ca2+ store-depletion of the endoplasmic reticulum. Previous studies using constitutively active Orai1 mutants gave rise to, but did not directly test, the hypothesis that STIM1-mediated Orai1 pore opening is accompanied by a global conformational change of all Orai TM helices within the channel complex. We prove that a local conformational change spreads omnidirectionally within the Orai1 complex. Our results demonstrate that these locally induced global, opening-permissive TM domain motions are indispensable for pore opening and require clearance of a series of Orai1 gating checkpoints. We discovered these gating checkpoints in middle and cytosolic extended TM domain regions. Our findings are based on a library of double point mutants that contain each one loss-of-function (LoF) with one gain-of-function (GoF) point mutation in a series of possible combinations. We demonstrated that an array of LoF mutations are dominant over most GoF mutations within the same as well as of an adjacent Orai subunit. We further identified inter- and intramolecular salt-bridge interactions of Orai subunits as a core element of an opening-permissive Orai channel architecture. Collectively, clearance and synergistic action of all these gating checkpoints are required to allow STIM1 coupling and Orai1 pore opening. Our results unravel novel insights in the preconditions of the unique fingerprint of CRAC channel activation, provide a valuable source for future structural resolutions and help to understand the molecular basis of disease-causing mutations.Hub proteins are central nodes in protein-protein interaction networks with critical importance to all living organisms. Recently, a new group of folded hub domains, the αα-hubs, was defined based on a shared αα-hairpin super-secondary structural foundation. The members PAH, RST, TAFH, NCBD and HHD are found in large proteins such as Sin3, RCD1, TAF4, CBP and harmonin, which organize disordered transcriptional regulators and membrane scaffolds in interactomes of importance to human diseases and plant quality. In this review, studies of structures, functions, and complexes across the αα-hubs are described and compared to provide a unified description of the group. This analysis expands the associated molecular concepts of "one domain - one superbinding site", motif-based ligand binding, and coupled folding and binding of intrinsically disordered ligands to additional concepts of importance to signal fidelity. These include context, motif reversibility, multivalency, complex heterogeneity, synergistic αα-hubligand folding, accessory binding-sites, and supramodules. We propose that these multifaceted protein-protein interaction properties are made possible by the characteristics of the αα-hub fold, including super-site properties, dynamics, variable topologies, accessory helices and malleability and abetted by adaptability of the disordered ligands. Critically, these features provide additional filters for specificity. With the presentations of new concepts, this review opens for new research questions addressing properties across the group, which are driven from concepts discovered in studies of the individual members. Combined, the members of the αα-hubs are ideal models for deconvoluting signal fidelity maintained by folded hubs and their interactions with intrinsically disordered ligands.Mutations in voltage-gated sodium channels (Navs) can cause alterations in pain sensation, such as chronic pain diseases like inherited erythromelalgia (IEM). selleck chemicals llc The IEM-causing mutation Nav1.7 p.I848T is known to induce a hyperpolarized shift in the voltage dependence of activation in Nav1.7. So far, however, the mechanism to explain this increase in voltage sensitivity remains unknown. In the present study, we show that phosphorylation of the newly introduced Thr residue explains the functional change. We expressed either wild type human Nav1.7, the I848T mutant, or other mutations in HEK293T cells and performed whole-cell patch-clamp electrophysiology. As the insertion of a Thr residue potentially creates a novel phosphorylation site for Ser/Thr kinases and because Nav1.7 had been shown in Xenopus oocytes to be affected by protein kinases C (PKC) and A (PKA), we used different non-selective and selective kinase inhibitors and activators to test the effect of phosphorylation on Nav1.7 in a human system. We identify PKC, but not PKA, to be responsible for the phosphorylation of T848 and thereby for the shift in voltage sensitivity. Introducing a negatively charged amino acid instead of the putative phosphorylation site mimics the effect on voltage gating to a lesser extent. 3D modelling using the published cryo-EM structure of human Nav1.7 showed that introduction of this negatively charged site seems to alter the interaction of this residue with surrounding amino acids and thus to influence channel function. These results could provide new opportunities for the development of novel treatment options for chronic pain patients.

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