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Contrary to initial assumptions, selective Caspase-3 inhibitors have not reached the clinical level, while QPI-1007, a siRNA directed against Caspase-2, is currently undergoing a multicentric phase III clinical study for the treatment of ischemic optic neuropathies.Cellular senescence has been now shown to be at the root of many degenerative processes that characterize ageing. Thus, in addition to an irreversible proliferative arrest following various stresses or inappropriate stimuli, cellular senescence leads to genetic, epigenetic, metabolic, structural and functional adaptations of the cell. Moreover, senescence phenotype spreads to the surrounding tissue through a specific secretory profile. Eliminating or blocking the action of senescent cells by senotherapeutic agents prevents tissue degeneration and improves the longevity in preclinical models. In this review, we will present the latest applications in senotherapy and discuss the very promising results of the first recently published clinical trials.Health is harmony, aging and its diseases (are) functional disharmony at the molecular, cellular and tissue levels. Our observations lead us to think that there seems to be a common cause and a common mechanism for aging and its many and diverse diseases. This common cause is the oxidative damage to particular proteins emerging from a combination of imperfect folding and oxidative stress. This common cause jointly goes with the biological clock common to various age-related diseases, whose the incidence increases exponentially over time and causes 90% of human mortality. Pharmacological interventions on the common cause could avoid and simultaneously attenuate all degenerative and malignant diseases, as it is the natural case of super-centenarians.The accumulation of senescent cells accompanies organismal aging. Senescent cells produce an inflammatory microenvironment that is conducive to the development of many age-related diseases. Here we describe the different situations leading to cellular senescence and show that these situations are frequently associated with DNA damage. We also discuss the intimate link between cell aging and perturbations in the nuclear envelope, namely in nuclear lamins, as seen in progeroid syndromes. Finally, we present evidence that these alterations are associated with DNA repair defects, the persistence of DNA damage, and an inflammatory phenotype.Aging is an alteration of our physiological capacities that is accompanied by an increased susceptibility to develop a wide range of diseases and which determines in large part our longevity. compound 991 in vitro Despite intensive research on the origin of aging, its etiology is still poorly understood. We discuss here the hypothesis that the telomere shortening, programmed to start at the end of embryogenesis in numerous tissues, couples development with aging by a time-dependent regulation of a set of interconnected processes essential for the somatic maintenance of genome, epigenome, metabolism, circadian clock and immunity.Optimal primary care sector performance is vital for ensuring the delivery of quality health services and effective clinical management of populations. The Primary Care Practice Improvement Tool (PC-PIT) incorporates subjective staff input and objective indicators to measure 13 elements of organisational performance. This study aimed to measure change in organisational performance for general practices using the PC-PIT with Primary Health Network (PHN) support. A pre-post design was used for changes in PC-PIT subjective and objective scores. Practices used results with PHN support to complete two Plan Do Study Act initiatives and were reassessed 9-months later. PC-PIT scales were dichotomised into lower and higher scores, with odds ratios used to determine effect size. Staff survey response rates were 55.4% at baseline and 50.1% at follow up. There were modest increases in the likelihood of staff rating several elements higher at follow up. When implemented with PHN support staff, the PC-PIT has the potential for effective, focussed and sustained quality improvement, with capacity to support Health Care Home model transition and implementation.The aim of this study was to improve follow-up laboratory testing for children infected by Shiga toxin-producing Escherichia coli (STEC) through the provision of an information sheet to healthcare providers in the province of Alberta, Canada. An information sheet recommending the performance of laboratory tests, every 24-48h until 3 days after diarrhoea resolves or the platelet count stabilises or begins to rise, was sent to all physicians who ordered a STEC-positive stool test as of 1 November 2016. The information sheet was only distributed to physicians in one of the province's five healthcare delivery zones (i.e. intervention zone). Medical records for children aged less then 18 years with laboratory confirmed STEC-positive stool samples between November 2014 and November 2018 were reviewed to determine the performance of recommended laboratory tests. Post-intervention, follow-up testing in all categories increased significantly for cases that occurred in the intervention zone, with odds ratios (OR) ranging from 3.02 (95% CI 1.35-6.78) to 3.94 (95% CI 1.70-9.16) when compared with pre-intervention. No increase in any of the laboratory testing categories was detected outside of the intervention zone. The provision of a targeted information sheet to healthcare providers improved the monitoring of STEC-infected children.This study evaluated the role of health literacy (HL) in the self-management of diabetes. A literature search was conducted in electronic databases and studies were selected using precise eligibility criteria. A meta-analysis was conducted to estimate the HL adequacy rate, factors affecting the adequacy of HL and correlations between HL and diabetes self-management variables. Thirty-three studies were included in the analysis. The HL adequacy rate was 67% (95% confidence interval (CI) 57, 76). Compared with patients with inadequate HL, patients with adequate HL were younger (mean difference -5.2 years; 95% CI -7.2, -3.2; P less then 0.00001), more likely to have a high school or higher level of education (odds ratio (OR) 8.39; 95% CI 5.03, 13.99]; P less then 0.00001) and were less likely to belong to a low-income group (OR 0.36; 95% CI 0.23, 0.56; P less then 0.00001). HL was positively correlated with self-monitoring (r=0.19; 95% CI 0.11, 0.27; P less then 0.00001), dietary and physical care (r=0.12; 95% CI 0.

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