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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Metabolically unhealthy obesity is associated with adipose tissue inflammation and increased risk of type 2 diabetes. Dysfunctional adipose tissue remodelling has been implicated in development of metabolically unhealthy obesity, but the pathogenesis remains poorly characterised. We hypothesised that in health, tissue inhibitor of metalloproteinases 3 (TIMP3) modulates adipose tissue remodelling by regulating extracellular matrix turnover and shedding of the adipogenic regulator DLK1, but that in adipose tissue inflammation it might drive development of metabolically unhealthy obesity. ⋯ British Heart Foundation, Diabetes Research and Wellness Foundation Open Funding 2011.
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Heart failure is a complex clinical syndrome that occurs at the end stage of heart disease. Despite advances in therapy for heart failure, improvement of clinical outcomes remains a challenge for physicians. The identification of treatment response early in the course of disease would be useful to improve management of these patients. The aim of this study was to identify novel biomarkers in plasma that could predict treatment response in patients with heart failure. ⋯ European Union's Seventh Framework Programme (BIOSTAT-CHF), John and Lucille van Geest Foundation.
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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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As the general population ages and life expectancy increases, health-care use by elderly people increases, including intensive care. Rationing and variation of access are ethically and politically challenging. We aimed to characterise the population-based incidence of intensive care unit (ICU) admissions of elderly people in Scotland; compare ICU admission and mortality between elderly and younger populations; and compare treatment intensity between these groups. ⋯ Funding assistance for AD's MPH from Scottish Intensive Care Society, Scottish Society of Anaesthetists, Edinburgh Anaesthetics Research and Education Fund.