OGG1 and MUTYH repair activities promote telomeric 8-oxoguanine induced senescence in human fibroblasts.

Telomeres are hypersensitive to the formation of the common oxidative lesion 8-oxoguanine (8oxoG), which impacts telomere stability and function. OGG1 and MUTYH glycosylases initiate base excision repair (BER) to remove 8oxoG or prevent mutation. Here, we show OGG1 loss or inhibition, or MUTYH loss, partially rescues telomeric 8oxoG-induced premature senescence and associated proinflammatory responses, while loss of both glycosylases causes a near complete rescue in human fibroblasts.

Refractory fungal infection: Three case reports highlighting good practice.

Refractory invasive fungal disease is a significant clinical problem, with high morbidity, mortality and costs. The complex causes of refractory infection include breakthrough infection due to antifungal resistance (both innate and acquired), suboptimal therapy and impaired immune responses in critically ill or immunocompromised patients. This case series details three reports on the identification and management of refractory fungal infections, two cases of azole resistance and one case of resistant candidiasis, highlighting the importance of accurate diagnosis, monitoring, implementation of biomarkers (serological markers, PCR), antifungal susceptibility testing and antifungal stewardship to optimise management and minimise risks of emergence of drug resistance.

A service evaluation of the implementation of a novel digital intervention for hypertension self-monitoring and management system in primary care (SHIP): protocol for a mixed methods study.

Background: Hypertension is a key risk factor for death and disability, and blood pressure reduction is associated with significant reductions in cardiovascular risk. Large trials have shown that interventions including self-monitoring of blood pressure can reduce blood pressure but real-world data from wider implementation are lacking.

Aim: The self-monitoring and management service evaluation in primary care (SHIP) study will evaluate a novel digital intervention for hypertension management and medication titration platform ("Hypertension-Plus") that is currently undergoing initial implementation into primary care in several parts of the UK.

Chemogenetic engagement of different GPCR signaling pathways segregates the orexigenic activity from the control of whole-body glucose metabolism by AGRP neurons.

Objective: The control of energy balance involves neural circuits in the central nervous system, including AGRP neurons in the arcuate nucleus of the hypothalamus (ARC). AGRP neurons are crucial for energy balance and their increased activity during fasting is critical to promote feeding behavior. The activity of these neurons is influenced by multiple signals including those acting on G-protein coupled receptors (GPCR) activating different intracellular signaling pathways.