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mes in the high-hyperopia subgroup.Aside from the first week postnatal, murine heart regeneration is restricted and responses to damage follow classic fibrotic remodeling. Recent transcriptomic analyses have suggested that significant cross talk with the sterile immune response could maintain a more embryonic-like signaling network that promotes acute, transient responses. However, with age, this response-likely mediated by neonatal yolk sac macrophages-then transitions to classical macrophage-mediated, cardiac fibroblast (CF)-based remodeling of the extracellular matrix (ECM) after myocardial infarction (MI). The molecular mechanisms that govern the change with age and drive fibrosis via inflammation are poorly understood. Using multiple ribonucleic acid sequencing (RNA-Seq) datasets, we attempt to resolve the relative contributions of CFs and macrophages in the bulk-healing response of regenerative (postnatal day 1) and nonregenerative hearts (postnatal day 8+). We performed an analysis of bulk RNA-Seq datasets from myocardium and cardiac fiys, and molecules that regulate this behavior are unclear. By comparing RNA-Seq datasets from regenerative mouse hearts and older, nonregenerative hearts, we are able to identify biological processes that are hallmarks of regeneration. We find that sterile inflammatory processes are upregulated in nonregenerative hearts, initiating profibrotic gene programs 3 days after myocardial infarction that can cause myocardial disease.Heart failure (HF) is a multifactorial syndrome that remains a leading cause of worldwide morbidity. Despite its high prevalence, only half of patients with HF respond to guideline-directed medical management, prompting therapeutic efforts to confront the molecular underpinnings of its heterogeneity. In the current study, we examined epigenetics as a yet unexplored source of heterogeneity among patients with end-stage HF. Specifically, a multicohort-based study was designed to quantify cardiac genome-wide cytosine-p-guanine (CpG) methylation of cardiac biopsies from male patients undergoing left ventricular assist device (LVAD) implantation. In both pilot (n = 11) and testing (n = 31) cohorts, unsupervised multidimensional scaling of genome-wide myocardial DNA methylation exhibited a bimodal distribution of CpG methylation found largely to occur in the promoter regions of metabolic genes. Among the available patient attributes, only categorical self-identified patient race could delineate this methylation sigoportionately affect metabolic signaling pathways. Socioeconomic factors are associated with racial differences in the cardiac methylome among men with end-stage heart failure.The detailed physiological consequences of aerobic training, in patients with hypertrophic cardiomyopathy (HCM), are not well understood. In athletes and nonathletes with HCM, there are two hypothetical concerns with respect to exercise exercise-related worsening of the phenotype (e.g., promoting hypertrophy and fibrosis) and/or triggering of arrhythmia. The former concern is unproven and animal studies suggest an opposite effect, where exercise has been shown to be protective. The main reason for exercise restriction in HCM is fear of exercise-induced arrhythmia. Although the safety of sports in HCM has been reviewed, even more recent data suggest a substantially lower risk for sudden cardiac death (SCD) in HCM than previously thought, and there is an ongoing debate about restrictions of exercise imposed on individuals with HCM. This review outlines the pathophysiology of HCM, the impact of acute and chronic exercise (and variations of exercise intensity, modality, and athletic phenotype) in HCM including changes in autonomic function, blood pressure, cardiac dimensions and function, and cardiac output, and the underlying mechanisms that may trigger exercise-induced lethal arrhythmias. It provides a critical evaluation of the evidence regarding risk of SCD in athletes and the potential benefits of targeted exercise prescription in adults with HCM. Finally, it provides considerations for personalized recommendations for sports participation based on the available data.Nicotinic receptors (NRs) play an important role in the cholinergic regulation of heart functions, and converging evidence suggests a diverse repertoire of NR subunits in the heart. A recent hypothesis about the plasticity of β NR subunits suggests that β2-subunits and β4-subunits may substitute for each other. In our study, we assessed the hypothetical β-subunit interchangeability in the heart at the level of mRNA. Using two mutant mice strains lacking β2 or β4 NR subunits, we examined the relative expression of NR subunits and other key cholinergic molecules. We investigated the physiology of isolated hearts perfused by Langendorff's method at basal conditions and after cholinergic and/or adrenergic stimulation. Lack of β2 NR subunit was accompanied with decreased relative expression of β4-subunits and α3-subunits. No other cholinergic changes were observed at the level of mRNA, except for increased M3 and decreased M4 muscarinic receptors. Isolated hearts lacking β2 NR subunit showed different dynamics in to a high dose of acetylcholine upon adrenergic stimulation.In this study, we investigated whether human umbilical cord mesenchymal stem cell (hUCMSC) fibrin patches loaded with nerve growth factor (NGF) poly(lactic-co-glycolic acid) (PLGA) nanoparticles could enhance the therapeutic potency of hUCMSCs for myocardial infarction (MI). In vitro, NGF significantly improved the proliferation of hUCMSCs and mitigated cytotoxicity and apoptosis under hypoxic injury. NGF also promoted the paracrine effects of hUCMSCs on angiogenesis and cardiomyocyte protection. The tyrosine kinase A (TrkA) and phosphoinositide 3-kinase (PI3K)-serine/threonine protein kinase (Akt) signaling pathways in hUCMSCs were involved in the NGF-induced protection. NGF PLGA nanoparticles continued to release NGF for at least 1 mo and also exerted a protective effect on hUCMSCs, the same with free NGF. In vivo, we treated MI mice with nothing (MI group), a cell-free fibrin patch with blank PLGA nanoparticles (MI + OP group), a cell-free fibrin patch with NGF nanoparticles (MI + NGF group), and hUCMSC fiial apoptosis and promote angiogenesis in the mouse heart after MI.There are currently no Food and Drug Administration-approved treatments for heart failure with preserved ejection fraction (HFpEF). Here we compared the effects of exercise with and without α/β-adrenergic blockade with carvedilol in Col4a3-/- Alport mice, a model of the phenogroup 3 subclass of HFpEF with underlying renal dysfunction. Alport mice were assigned to the following groups no treatment control (n = 29), carvedilol (n = 11), voluntary exercise (n = 9), and combination carvedilol and exercise (n = 8). Selumetinib mw Cardiac function was assessed by echocardiography after 4-wk treatments. Running activity of Alport mice was similar to wild types at 1 mo of age but markedly reduced at 2 mo (1.3 ± 0.40 vs. 4.5 ± 1.02 km/day, P less then 0.05). There was a nonsignificant trend for increased running activity at 2 mo by carvedilol in the combination treatment group. Combination treatments conferred increased body weight of Col4a3-/- mice (22.0 ± 1.18 vs. 17.8 ± 0.29 g in untreated mice, P less then 0.01), suggesting e. Carvedilol alone or in combination with exercise also improved kidney function. Molecular analyses indicate that the observed improvements in cardiorenal functions were mediated at least in part by effects on serum osteopontin and related inflammatory cytokine cascades. The work presents new potential therapeutic targets and approaches for HFpEF.African American (AA) individuals are at a greater risk for the development of cardiovascular complications, such as hypertension, compared with European Americans (EAs). Higher vagally mediated heart rate variability (HRV) is typically associated with lower blood pressure (BP) and total peripheral resistance (TPR). However, research has yet to examine the differential impact of HRV on longitudinal hemodynamic activity between AAs and EAs. We sought to rectify this in a sample of 385 normotensive youths (207 AAs, 178 EAs; mean age 23.16 ± 2.9 yr). Individuals participated in two laboratory evaluations spanning approximately 6 yr. Bioimpedance was used to assess HRV at time 1 and cardiac output at both time 1 and time 2. Mean arterial pressure (MAP) was measured at both time points via an automated BP machine. TPR was calculated as MAP divided by cardiac output. Results showed AAs to have higher BP and higher TPR at time 2 compared with EAs, independent of several important covariates. Also, higher HRV at time 1 significantly predicted both lower TPR and BP at time 2 among EAs only; these associations were attenuated and not significant in AAs. HRV did not significantly predict cardiac output at time 2 in the full sample or split by ethnicity. Our findings highlight that AAs show TPR mediated long-term increases in BP irrespective of resting HRV, providing a physiological pathway linking AAs with a greater risk for mortality and morbidity from hypertension and potentially other cardiovascular disease.NEW & NEWSWORTHY African Americans and European Americans differ in hemodynamics underlying long-term blood pressure regulation. Over 6 yr, African Americans show total peripheral resistance-mediated increases in blood pressure compared with European Americans. Higher heart rate variability predicts lower blood pressure and total peripheral resistance 6 yr later in European Americans but not African Americans.In Brazil, the increasing prevalence of HIV infection in young people makes it critical to know its distribution in university communities. In this cross-sectional study, we evaluated the impact of STI/HIV testing campaigns on university campuses from 2013 to 2017. The participants took part in rapid testing for HIV, syphilis, hepatitis B and C, and counseling sessions. A total of 2691 people participated in the campaigns. Of these, 79.4% were single, and 50.3% were women. The median age was 24 years old, and 77.9% of participants had ≥12 years of formal education. Most reported having unprotected sex in the last year (87.4%). The positivity rates for HIV, syphilis, hepatitis B virus, and hepatitis C virus were 0.56%, 1.20%, 0.19%, and 0.11%, respectively. The characteristics associated with HIV infection were being men who have sex with men (MSM) (aOR = 12.06; 95% CI = 3.83-37.99) and having less then 12 years of schooling (aOR = 3.28; 95% CI = 1.03-10.38). Factors associated with syphilis seropositivity were older age (aOR = 1.06; 95% CI = 1.03-1.09), multiple partners (aOR = 2.44; 95% CI = 1.08-5.50), and being MSM (aOR = 5.40; 95% CI = 2.49-11.72). Positivity for hepatitis B tended to decrease with the years of testing (p = 0.023) and for hepatitis C to increase with age (p = 0.035). Our study observed a high vulnerability to HIV and syphilis infection in a university community, which needs an early prevention strategy, including regular testing, continuing sexual education, easy access to condoms, and pre- and postexposure HIV prophylaxis.

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