Sirtuins family as a target in endothelial cell dysfunction: implications for vascular ageing.

The vascular endothelium is a protective barrier between the bloodstream and the vasculature that may be disrupted by different factors such as the presence of diseased states. Diseases like diabetes and obesity pose a great risk toward endothelial cell inflammation and oxidative stress, leading to endothelial cell dysfunction and thereby cardiovascular complications such as atherosclerosis. Sirtuins are NAD+-dependent histone deacetylases that are implicated in the pathophysiology of cardiovascular diseases, and they have been identified to be important regulators of endothelial cell function. A handful of recent studies suggest that disbalance in the regulation of endothelial sirtuins, mainly sirtuin 1 (SIRT1), contributes to endothelial cell dysfunction. Herein, we summarize how SIRT1 and other sirtuins may contribute to endothelial cell function and how presence of diseased conditions may alter their expressions to cause endothelial dysfunction. Moreover, we discuss how the beneficial effects of exercise on the endothelium are dependent on SIRT1. These mainly include regulation of signaling pathways related to endothelial nitric oxide synthase phosphorylation and nitric oxide production, mitochondrial biogenesis and mitochondria-mediated apoptotic pathways, oxidative stress and inflammatory pathways. Sirtuins as modulators of the adverse conditions in the endothelium hold a promising therapeutic potential for health conditions related to endothelial dysfunction and vascular ageing.

Low implementation of Xpert MTB/RIF among HIV/TB co-infected adults in the International epidemiologic Databases to Evaluate AIDS (IeDEA) program.

OBJECTIVE: Xpert MTB/RIF is recommended by the World Health Organization (WHO) as the initial tuberculosis (TB) diagnostic test in individuals suspected of HIV-associated TB. We sought to evaluate field implementation of Xpert among a cohort of HIV/TB co-infected individuals, including availability, utilization and outcomes. DESIGN: Observational cohort study (patient-level data) and cross-sectional study (site-level Xpert availability data). METHODS: Data were collected at 30 participating International epidemiologic Databases to Evaluate AIDS (IeDEA) sites in 18 countries from January 2012-January 2016. All patients were HIV-infected and diagnosed with TB, either bacteriologically or clinically, and followed until a determination of TB treatment outcome. We used multivariable modified Poisson regression to estimate adjusted relative risk (RR) and 95% confidence intervals for unfavorable TB treatment outcomes. RESULTS: Most sites (63%) had access to Xpert, either in the clinic (13%), in the same facility (20%) or offsite (30%). Among 2722 HIV/TB patients included, median age was 35.4 years and 41% were female; BMI and CD4 count were low. Overall, most patients (76%) received at least one TB test; 45% were positive. Only 4% of all patients were tested using Xpert: 64% were Xpert-positive, 13% showed rifampicin (RIF) resistance and 30% were extrapulmonary (EPTB) or both pulmonary-EPTB. Treatment outcomes were mostly favorable (77%) and we found little association between Xpert use and an unfavorable TB treatment outcome (RR 1.25, 95%CI: 0.83, 1.90). CONCLUSIONS: In this cohort, Xpert utilization was low even though the majority of sites had access to the test. Our findings show the need for expanded implementation and further research exploring barriers to use in low-resource settings.