Lancet
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Implementation of the National Early Warning Score in the National Health Service (NHS) has renewed focus on prompt identification and referral of the deteriorating ward patient. A large body of published work suggests that delay in both referral and admission to critical care can be associated with poor outcomes. We sought to explore factors associated with early provision of respiratory support in a cohort of deteriorating ward patients referred to the critical care team. ⋯ Wellcome Trust, National Institute for Health Service Support Costs, Intensive Care National Audit & Research Centre.
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Innate immune cells are major targets of glucocorticoids as anti-inflammatory therapies. Glucocorticoids are metabolic hormones that provide natural feedback regulation of immune function. They are widely prescribed, but use is restricted by side-effects. Much of our knowledge about how glucocorticoids work comes from studies in mice. However, since mice are imperfect models of human macrophage biology, for example in inflammation, whether this knowledge can be directly translated to man is uncertain. We aimed to address this uncertainty. ⋯ Wellcome Trust.
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The mechanism responsible for left ventricular dysfunction after cardiac surgery is only partly understood. In isolated rat hearts subjected to an ischaemia-reperfusion protocol, left ventricular dysfunction was associated with uncoupling of endothelial nitric oxide synthase (NOS) activity secondary to oxidation of the NOS cofactor, tetrahydrobiopterin (BH4). Here we investigated the effect of cardiopulmonary bypass and reperfusion on myocardial nitroso-redox balance in patients undergoing cardiac surgery. ⋯ British Heart Foundation.
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Enhanced complement C3 incorporation into the fibrin network in diabetes is one mechanism for impaired fibrinolysis and increased thrombosis risk in this condition. Our aim was to develop new strategies to modulate fibrinolysis in diabetes by interfering with fibrin-C3 interaction. ⋯ Sir Jules Thorn Charitable Trust.
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DNA damage transactivates tumour protein p53 (TP53)-regulated surveillance, crucial in suppressing tumorigenesis. TP53 mediates this process directly by transcriptionally modulating gene and microRNA (miRNA) expression and indirectly by regulating miRNA biogenesis. However, the role of TP53 in regulating miRNA-AGO2 loading and global changes in AGO2 binding to its gene targets in response to DNA damage are unknown. These processes might be novel mechanisms by which TP53 regulates miRNAs in response to DNA damage. ⋯ UK Medical Research Council, Action Against Cancer.