Mammalian biology adapts to physical activity but the molecular mechanisms sensing the activity remain enigmatic. Recent studies have revealed how Piezo1 protein senses mechanical force to enable vascular development. Here, we address Piezo1 in adult endothelium, the major control site in physical activity. Mice without endothelial Piezo1 lack obvious phenotype but close inspection reveals a specific effect on endothelium-dependent relaxation in mesenteric resistance artery. Strikingly, the Piezo1 is required for elevated blood pressure during whole body physical activity but not blood pressure during inactivity. Piezo1 is responsible for flow-sensitive non-inactivating non-selective cationic channels which depolarize the membrane potential. As fluid flow increases, depolarization increases to activate voltage-gated Ca2+ channels in the adjacent vascular smooth muscle cells, causing vasoconstriction. Physical performance is compromised in mice which lack endothelial Piezo1 and there is weight loss after sustained activity. The data suggest that Piezo1 channels sense physical activity to advantageously reset vascular control.

For patients hospitalized with ACS in England and Wales, there have been substantial reductions in in-hospital mortality rates from 2003 to 2010 across all age groups. The temporal improvements in mortality were similar for sex and type of acute myocardial infarction. Age-dependent inequalities in the management of ACS were apparent.

♦ Background:Patients are satisfied with their kidney care but want more support in making dialysis choices. Predialysis leaflets vary across services, with few being sufficient to enable patients' informed decision making. We describe the acceptability of a patient decision aid and feasibility of evaluating its effectiveness within usual predialysis practice.♦ Methods:Prospective non-randomized comparison design, Usual Care or Usual Care Plus Yorkshire Dialysis Decision Aid Booklet (+YoDDA), in 6 referral centers (Yorkshire-Humber, UK) for patients with sustained deterioration of kidney function. Consenting (C) patients completed questionnaires after predialysis consultation (T1), and 6 weeks later (T2). Measures assessed YoDDA's utility to support patients' decisions and integration within usual care.♦ Results:Usual Care (n = 105) and +YoDDA (n = 84) participant characteristics were similar: male (62%), white (94%), age (mean = 62.6; standard deviation [SD] 14.4), kidney disease severity (glomerular filtration rate [eGFR] mean = 14.7; SD 3.7); decisional conflict was < 25; choice-preference for home versus hospital dialysis approximately 50:50. Patients valued receiving YoDDA, reading it on their own (96%), and sharing it with family (72%). The +YoDDA participants had higher scores for understanding kidney disease, reasoning about options, feeling in control, sharing their decision with family. Study engagement varied by center (estimated range 14 – 49%; mean 45%); participants varied in completion of decision quality measures.♦ Conclusions:Receiving YoDDA as part of predialysis education was valued and useful to patients with worsening kidney disease. Integrating YoDDA actively within predialysis programs will meet clinical guidelines and patient need to support dialysis decision making in the context of patients' lifestyle.

This study reports preliminary evidence suggesting that the higher AMD risk genotypes in CFH, VEGF and HTRA1 may influence the short-term response to treatment with ranibizumab for neovascular AMD.

Many patients have ilio-femoral vessel anatomy unsuitable for conventional transfemoral (TF) trans-catheter aortic valve implantation (TAVI). Safe and practical alternatives to the TF approach are therefore needed. This study compared outcomes of alternative non-femoral routes, trans-apical (TA), direct aortic (DA) and subclavian (SC), with standard femoral access. In this retrospective study, data from 3,962 patients in the UK TAVI registry were analysed. All patients who received TAVI via a femoral, subclavian, transapical or direct aortic approach were eligible for inclusion. The primary outcome measure was survival up to two years. Median Logistic EuroSCORE was similar for SC, DA, and TA, but significantly lower in the TF cohort (22.1% vs 20.3% vs 21.2% vs 17.0% respectively, p<0.0001). Estimated oneyear survival was similar for TF (84.6±0.7%) and SC (80.5±3%, p=0.27), but significantly worse for TA (74.7±1.6%, p<0.001) and DA (75.2±3.3%, p<0.001). A Cox proportional hazard model was used to analyse survival up to 2-years. Survival in the SC group was not significantly different to the TF group (HR 1.22, 95% CI 0.88-1.70, p=0.24). In contrast, survival in the TA (HR 1.74, 95% CI 1. 43-2.11;p<0.001) and DA (HR 1.55, 95% CI 1.13-2.14; p<0.01) cohorts was significantly reduced compared to TF. In conclusion, trans-apical and direct aortic TAVI were associated with similar survival, both significantly worse than with the trans-femoral route. In contrast, subclavian access was not significantly different to trans-femoral, and may represent the safest non-femoral access route for TAVI.