Lancet
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Incomplete understanding of mechanisms and clinicopathobiological heterogeneity in asthma hinders research progress. Pathogenic roles for T-helper-type 17 (Th17) cells and invariant T cells implied by murine data have yet to be assessed in man. We aimed to investigate the role of Th17 and mucosal associated invariant T (MAIT) cells in airway inflammation; to characterise associations between diverse clinical and immunological features of asthma; and to identify novel multidimensional asthma endotypes. ⋯ Wellcome Trust.
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Preterm infants are at increased risk of cardiometabolic disease in later life. Extrauterine growth restriction, catch-up growth, altered adiposity, and abnormal hypothalamic-pituitary-adrenal axis activity could be predisposing factors. Altered DNA methylation (5-methylcytosine, 5mC) might be one underlying mechanism. We hypothesised that preterm infants have altered 5mC at the linked differentially methylated region 2 (DMR2) of IGF2 and the H19 imprinting control region (H19 ICR) compared with term infants over the first year of life. ⋯ Chief Scientist Office of the Scottish Government.
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Acute respiratory distress syndrome (ARDS) is characterised by diffuse neutrophil-mediated alveolar inflammation. Recently, we demonstrated that blood polymorphonuclear leucocytes (PMNs) in ARDS are basally activated, and exhibit aberrant oxidative burst and survival responses. The molecular mechanisms governing ARDS PMN function and longevity are incompletely understood. We aimed to use genome-wide transcriptional profiling of ARDS blood PMNs to explore underlying disease mechanisms and identify therapeutic targets aimed at manipulating PMN function and longevity. ⋯ National Institute for Health Research, GlaxoSmithKline.
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Necrotising fasciitis due to invasive group A streptococcus (iGAS) is frequently associated with type emm1 isolates, with an attendant mortality of 40%. Some cases occur in previously healthy individuals with a history of upper respiratory tract infection, soft tissue contusion, and no obvious portal of entry. Using a new model of mild contusion injury, we set out to determine the effect of contusion on iGAS bacterial burden, phenotype, and host cytokine response. ⋯ Royal Army Medical Corps, Surgeon General's Research Strategy Group, Ministry of Defence.
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Exercise capacity in chronic obstructive pulmonary disease (COPD) is limited by both breathlessness and leg muscle fatigue. Neural respiratory drive, measured as diaphragm electromyogram (EMGdi) activity expressed as a proportion of maximum (EMGdi%max), quantifies the mechanical load on the respiratory muscles and relates closely to breathlessness. We tested the hypothesis that end-exercise EMGdi%max would be higher in patients stopping because of breathlessness than in those limited by leg fatigue. ⋯ None.