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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Epilepsy is characterised by disturbed neuronal activity in the brain rendering it more susceptible to seizures. An understanding of the molecular mechanisms by which the balance between excitability and inhibition in neuronal networks is controlled will help to devise better treatment options. Hyperpolarising synaptic inhibition through GABAA (γ aminobutyric acid type A) and glycine receptors depends on the presence of the neuronal cation-chloride-cotransporter protein, KCC2. Several transcriptional and post-transcriptional mechanisms have been shown to regulate KCC2 and thereby affect the polarity and efficacy of inhibitory synaptic transmission. However, it is unknown whether regulation of KCC2 enables the transporter to attain different levels of activity, thus allowing a neuron to modulate the strength of inhibitory synaptic transmission to its changing requirements. We therefore investigated whether phosphorylation can allow KCC2 to achieve distinct levels of intracellular chloride ion concentrations in neurons. ⋯ Royal Society.
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Uniquely, alloantigen is recognised by two pathways: as intact antigen on the surface of donor antigen-presenting cells (direct) and as self-restricted processed allopeptide (indirect). The indirect pathway is believed to be longlasting, and is generally considered to be a single entity. Here we address how indirect responses against different alloantigens differ in their strength and longevity, and how this knowledge could be used to direct immunoregulatory therapy with antigen-specific regulatory T cells (Tregs). ⋯ Wellcome Trust Clinical Research Training Fellowship.
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Patients with loss-of-function mutation in neurokinin B (NKB) and its receptor show hypogonadotropic hypogonadism characterised by failure to progress through puberty, indicating the involvement of this newly described hypothalamic peptide in human reproduction. However the role of NKB in regulating ovarian function in adult women is unknown. We tested the hypothesis that a NKB antagonist would decrease gonadotropin secretion and inhibit folliculogenesis in healthy women. ⋯ Wellcome Trust through the Scottish Translational and Therapeutics Initiative.
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The management of atrial fibrillation remains a challenge. This condition remodels atrial electrical properties, which promote resistance to treatment. Although remodelling has long been a therapeutic target in atrial fibrillation, its causes remain incompletely understood. We aimed to evaluate the role of miR-31-dependent reduction in dystrophin and neuronal nitric oxide synthase (nNOS, also known as NOS1) on atrial electrical properties and atrial fibrillation inducibility. ⋯ British Heart Foundation (BHF) Programme grant (for BC and XL), BHF Centre of Excellence in Oxford (SR), Leducq Foundation (in part for BC and SR), the European Union's seventh Framework Programme Grant Agree.