Kirklandarildsen6444

A frailty index (FI) counts health deficit accumulation. Besides traditional risk factors, it is unknown whether the health deficit burden is related to the appearance of cardiovascular disease. In order to answer this question, the same multidimensional FI looking at 45-health deficits was serially calculated per participant at 4 time periods (0-16, 19-44, 45-54 and 60-64 years) using data from the 1946 Medical Research Council (MRC) British National Survey of Health and Development (NSHD)-the world's longest running longitudinal birth cohort with continuous follow-up. From these the mean and total FI for the life-course, and the step change in deficit accumulation from one time period to another was derived. Echocardiographic data at 60-64 years provided ejection fraction (EF), left ventricular mass indexed to body surface area (LVmassi, BSA), myocardial contraction fraction indexed to BSA (MCFi) and E/e'. Generalized linear models assessed the association between FIs and echocardiographic parameters after adjustment for relevant covariates. 1375 participants were included. For each single new deficit accumulated at any one of the 4 time periods, LVmassi increased by 0.91-1.44% (p  less then  0.013), while MCFi decreased by 0.6-1.02% (p  less then  0.05). A unit increase in FI at age 45-54 and 60-64, decreased EF by 11-12% (p  less then  0.013). A single health deficit step change occurring between 60 and 64 years and one of the earlier time periods, translated into higher odds (2.1-78.5, p  less then  0.020) of elevated LV filling pressure. Thus, the accumulation of health deficits at any time period of the life-course associates with a maladaptive cardiac phenotype in older age, dominated by myocardial hypertrophy and poorer function.Seamounts and oceanic islands of the Chilean Exclusive Economic Zone at the intersection of the Nazca and Salas y Gómez ridges lie within one of the least explored areas in the world. The sparse information available, mainly for seamounts outside Chilean jurisdiction and shallow-water fauna of the Desventuradas Islands, suggests that the area is a hotspot of endemism. This apparent uniqueness of the fauna motivated the creation of the large Nazca-Desventuradas Marine Park (NDMP, ~ 300,000 km2) around the small islands San Felix and San Ambrosio in 2015. We report for the first time a detailed description of benthic microhabitats (i.e., centimeter to meter scale), macrohabitats (i.e., meter to kilometer-scale) and associated megafauna within the NDMP. Descriptions were based on analysis of fauna collected by trawling and ROV video observations from ~ 50 to 370 m depth. Rocky, coarse sand and silty sediment bottom habitats were observed at island slopes. In contrast, rocky and coarse sandy bottom habitats with a predominance of rhodoliths, thanatocoenosis, and other biogenic components were observed at seamounts. Mobile fauna and predators dominated the oceanic islands and nearby seamounts, whereas seamounts farther from the islands were dominated by sessile and hemisessile fauna that were mainly suspension and deposit feeders. Based on the register of 118 taxonomic units, our results provide an expanded and updated baseline for the benthic biodiversity of NDMP habitats, which seemed pristine, without evidence of trawling or anthropogenic debris.Doxorubicin (DOX)-induced cardiotoxicity in chemotherapy is a major treatment drawback. Clinical trials on the cardioprotective effects of exercise in cancer patients have not yet been published. Thus, we conducted a systematic review and meta-analysis of preclinical studies for to assess the efficacy of exercise training on DOX-induced cardiomyopathy. We included studies with animal models of DOX-induced cardiomyopathy and exercise training from PubMed, Web of Sciences and Scopus databases. The outcome was the mean difference (MD) in fractional shortening (FS, %) assessed by echocardiography between sedentary and trained DOX-treated animals. Trained DOX-treated animals improved 7.40% (95% CI 5.75-9.05, p  less then  0.001) in FS vs. sedentary animals. Subgroup analyses revealed a superior effect of exercise training execution prior to DOX exposure (MD = 8.20, 95% CI 6.27-10.13, p = 0.010). The assessment of cardiac function up to 10 days after DOX exposure and completion of exercise protocol was also associated with superior effect size in FS (MD = 7.89, 95% CI 6.11-9.67, p = 0.020) vs. an echocardiography after over 4 weeks. Modality and duration of exercise, gender and cumulative DOX dose did were not individually associated with changes on FS. Exercise training is a cardioprotective approach in rodent models of DOX-induced cardiomyopathy. Exercise prior to DOX exposure exerts greater effect sizes on FS preservation.Cerebral ischemia (CI) is a severe cause of neurological dysfunction and mortality. Sirtuin-1 (Silent information regulator family protein 1, SIRT1), an oxidized nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, plays an important role in protection against several neurodegenerative disorders. The present study aims to investigate the protective role of SIRT1 after CI in experimental young and aged rats and humans. Also, the study examines the possible regulatory mechanisms of neuronal death in CI settings. Immunoblotting and immunohistochemistry were used to evaluate changes in the expression of SIRT1, JNK/ERK/MAPK/AKT signaling, and pro-apoptotic caspase-3 in experimental rats and CI patients. Darovasertib clinical trial The study findings demonstrated that, in aged experimental rats, SIRT1 activation positively influenced JNK and ERK phosphorylation and modulated neuronal survival in AKT-dependent manner. Further, the protection conferred by SIRT1 was effectively reversed by JNK inhibition and increased pro-apoptotic caspase-3 expression. In young experimental rats, SIRT1 activation decreased the phosphorylation of stress-induced JNK, ERK, caspase-3, and increased the phosphorylation of AKT after CI. Inhibition of SIRT1 reversed the protective effect of resveratrol. More importantly, in human patients, SIRT1 expression, phosphorylation of JNK/ERK/MAPK/AKT signaling and caspase-3 were up-regulated. In conclusion, SIRT1 could possibly be involved in the modulation of JNK/ERK/MAPK/AKT signaling pathway in experimental rats and humans after CI.