daptive coping strategies.Emergency clinicians worldwide are demonstrating increasing concern about the effect of climate change on the health of the populations they serve. The movement for sustainable healthcare is being driven by the need to address the climate emergency. SBE-β-CD cost Globally, healthcare contributes significantly to carbon emissions, and the healthcare sector has an important role to play in contributing to decarbonisation of the global economy. In this article, we consider the implications for emergency medicine of climate change, and suggest ways to improve environmental sustainability within emergency departments. We identify examples of sustainable clinical practice, as well as outlining research proposals to address the knowledge gap that currently exists in the area of provision of environmentally sustainable emergency care.Overview of Curtis HJ, Walker AJ, MacKenna B, et al Prescription of suboptimal statin treatment regimens a retrospective cohort study of trends and variation in English primary care. Br J Gen Pract 2020;70e525-e533.A major limitation to understanding the associations of human leukocyte antigen (HLA) and CD8+ and CD4+ T cell receptor (TCR) genes with disease pathophysiology is the technological barrier of identifying which HLA molecules, epitopes, and TCRs form functional complexes. Here, we present a high-throughput epitope identification system that combines capture of T cell-secreted cytokines by barcoded antigen-presenting cells (APCs), cell sorting, and next-generation sequencing to identify class I- and class II-restricted epitopes starting from highly complex peptide-encoding oligonucleotide pools. We engineered APCs to express anti-cytokine antibodies, a library of DNA-encoded peptides, and multiple HLA class I or II molecules. We demonstrate that these engineered APCs link T cell activation-dependent cytokines with the DNA that encodes the presented peptide. We validated this technology by showing that we could select known targets of viral epitope-, neoepitope-, and autoimmune epitope-specific TCRs, starting from mixtures of peptide-encoding oligonucleotides. Then, starting from 10 TCRβ sequences that are found commonly in humans but lack known targets, we identified seven CD8+ or CD4+ TCR-targeted epitopes encoded by the human cytomegalovirus (CMV) genome. These included known epitopes, as well as a class I and a class II CMV epitope that have not been previously described. Thus, our cytokine capture-based assay makes use of a signal secreted by both CD8+ and CD4+ T cells and allows pooled screening of thousands of encoded peptides to enable epitope discovery for orphan TCRs. Our technology may enable identification of HLA-epitope-TCR complexes relevant to disease control, etiology, or treatment.Therapeutic options for autoimmune diseases typically consist of broad and targeted immunosuppressive agents. However, sustained clinical benefit is rarely achieved, as the disease phenotype usually returns after cessation of treatment. To better understand tissue-resident immune memory in human disease, we investigated patients with atopic dermatitis (AD) who underwent short-term or long-term treatment with the IL-4Rα blocker dupilumab. Using multi-omics profiling with single-cell RNA sequencing and multiplex proteomics, we found significant decreases in overall skin immune cell counts and normalization of transcriptomic dysregulation in keratinocytes consistent with clearance of disease. However, we identified specific immune cell populations that persisted for up to a year after clinical remission while being absent from healthy controls. These populations included LAMP3+CCL22+ mature dendritic cells, CRTH2+CD161+ T helper (“TH2A”) cells, and CRTAM+ cytotoxic T cells, which expressed high levels of CCL17 (dendritic cells) and IL13 (T cells). TH2A cells showed a characteristic cytokine receptor constellation with IL17RB, IL1RL1 (ST2), and CRLF2 expression, suggesting that these cells are key responders to the AD-typical epidermal alarmins IL-25, IL-33, and TSLP, respectively. We thus identified disease-linked immune cell populations in resolved AD indicative of a persisting disease memory, facilitating a rapid response system of epidermal-dermal cross-talk between keratinocytes, dendritic cells, and T cells. This observation may help to explain the disease recurrence upon termination of immunosuppressive treatments in AD, and it identifies potential disease memory-linked cell types that may be targeted to achieve a more sustained therapeutic response.

Although the literature supporting the use of point-of-care ultrasound (POCUS) continues to grow, incomplete reporting of primary diagnostic accuracy studies has previously been identified as a barrier to translating research into practice and to performing unbiased systematic reviews. This study assesses POCUS investigator and journal editor attitudes towards barriers to adhering to the Standards for Reporting of Diagnostic Accuracy Studies (STARD) 2015 guidelines.

Two separate surveys using a 5-point Likert scale were sent to POCUS study investigators and journal editors to assess for knowledge, attitude and behavioural barriers to the complete reporting of POCUS research. Respondents were identified based on a previous study assessing STARD 2015 adherence for POCUS studies published in emergency medicine, anaesthesia and critical care journals. Responses were anonymously linked to STARD 2015 adherence data from the previous study. Written responses were thematically grouped into the following categoriepen Science Framework Registry (https//osf.io/5pzxs/).TRAIL (Tnfsf10/TRAIL/CD253/Apo2L) is an important immune molecule that mediates apoptosis. TRAIL can play key roles in regulating cell death in the tumor and autoimmune microenvironments. However, dissecting TRAIL function remains difficult because of the lack of optimal models. We have now generated a conditional knockout (Tnfsf10L/L) for cell type-specific analysis of TRAIL function on C57BL/6, BALB/c, and NOD backgrounds. Previous studies have suggested a role for TRAIL in regulatory T cell (Treg)-mediated suppression. We generated mice with a Treg-restricted Tnfsf10 deletion and surprisingly found no impact on tumor growth in C57BL/6 and BALB/c tumor models. Furthermore, we found no difference in the suppressive capacity of Tnfsf10-deficient Tregs and no change in function or proliferation of T cells in tumors. We also assessed the role of TRAIL on Tregs in two autoimmune mouse models the NOD mouse model of autoimmune diabetes and the myelin oligodendrocyte glycoprotein (MOG) C57BL/6 model of experimental autoimmune encephalomyelitis.