Alzheimer's disease (AD) is a neurodegenerative disorder, and its pathogenesis is not fully known. Although there are several hypotheses, such as neuroinflammation, tau hyperphosphorylation, amyloid-β plaques, neurofibrillary tangles, and oxidative stress, none of them completely explain the origin and progression of AD. Emerging evidence suggests that gut microbiota and epigenetics can directly influence the pathogenesis of AD via their effects on multiple pathways, including neuroinflammation, oxidative stress, and amyloid protein. Various gut microbes such as Actinobacteria, Bacteroidetes, E. coli, Firmicutes, Proteobacteria, Tenericutes, and Verrucomicrobia are known to play a crucial role in the pathogenesis of AD. These microbes and their metabolites modulate various physiological processes that contribute to AD pathogenesis, such as neuroinflammation and other inflammatory processes, amyloid deposition, cytokine storm syndrome, altered BDNF and NMDA signaling, impairing neurodevelopmental processes. Likewise, epigenetic markers associated with AD mainly include histone modifications and DNA methylation, which are under the direct control of a variety of enzymes, such as acetylases and methylases. The activity of these enzymes is dependent upon the metabolites generated by the host's gut microbiome, suggesting the significance of epigenetics in AD pathogenesis. It is interesting to know that both gut microbiota and epigenetics are dynamic processes and show a high degree of variation according to diet, stressors, and environmental factors. The bidirectional relation between the gut microbiota and epigenetics suggests that they might work in synchrony to modulate AD representation, its pathogenesis, and progression. They both also provide numerous targets for early diagnostic biomarkers and for the development of AD therapeutics. This review discusses the gut microbiota and epigenetics connection in the pathogenesis of AD and aims to highlight vast opportunities for diagnosis and therapeutics of AD.Thanks to the improvement in mitral regurgitation (MR) diagnostic and therapeutic management, with the introduction of minimally invasive techniques which have considerably reduced the individual surgical risk, the optimization of the timing for MR "open" or percutaneous surgical treatment has become a main concern which has highly raised scientific interest. In fact, the current indications for intervention in MR, especially in asymptomatic patients, rely on echocardiographic criteria with high severity cut-offs that are fulfilled only when not only mitral valve apparatus but also the cardiac chambers' structure and function are severely impaired, which results in poor benefits for post-operative clinical outcome. This led to the need of new indices to redefine the optimal surgical timing in these patients. Speckle tracking echocardiography provides early markers of cardiac dysfunction due to subtle myocardial impairment; therefore, it could offer pivotal information in this setting. In fact, left ventricular and left atrial strains have already shown evidence about their usefulness in recognizing MR impact not only on symptoms and quality of life but also on cardiovascular events and new-onset atrial fibrillation in these patients. Moreover, right ventricular strain could be used to identify those patients with advanced cardiac damage and different grades of right ventricular dysfunction, which entails higher risks for cardiac surgery that could overweigh surgical benefits. Divarasib This review aims to describe the importance of reconsidering the timing of intervention in MR and to analyze the potential additive value of speckle tracking echocardiography in this clinical setting.Obesity has been linked with heart failure (HF) with preserved left ventricular (LV) ejection fraction (HFpEF). This link has been attributed to obesity-induced metabolic and inflammatory disturbances leading to HFpEF. However, HF is a syndrome in which disease evolvement is associated with a dynamic unraveling of functional and structural changes leading to unique disease trajectories, creating a spectrum of phenotypes with overlapping distinct characteristics extending beyond the LV ejection fraction (LVEF). In this regard, despite quantitative differences between the two extremes (HFpEF and HF with reduced LVEF, HFrEF), there is important overlap between the phenotypes along the entire spectrum. In this paper, we describe the systemic pro-inflammatory state that is present throughout the HF spectrum and emphasize that obesity intertwines with HF beyond the LVEF construct. The efficacy of inhaled budesonide for managing moderate-to-severe acute exacerbations in children is not clear. Therefore, this study aimed to evaluate hospital admission rates, need for use of systemic corticosteroids, length of hospital stay and adverse events when inhaled budesonide is added to standard pediatric emergency department management of moderate-to-severe acute exacerbations of asthma. A systematic search was conducted in PubMed, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials) and Google scholar databases. Randomized controlled trials that evaluated the effect of nebulized budesonide in moderate-to-severe acute exacerbations of asthma in pediatric patients were included for this meta-analysis. Statistical analysis was done using STATA version 13.0. A total of 16 RCTs were included. Children receiving nebulized budesonide had 43% lower risk of being hospitalized (RR 0.57; 95% CI, 0.39; 0.85)and66% lower risk ofrequiring systemic corticosteroids(RR 0.34; 95 % CI, 0.21; 0.55) compared with those receiving placebo. There were no differences in the length of hospital stay (Hedges's g standardized mean difference - 1.53; 95% CI, - 3.64; 0.58) and risk of adverse events (RR 0.87, 95% CI; 0.65; 1.17) between the two groups. There was no evidence of publication bias for any of the outcomes considered. The findings of this meta-analysis support the use of inhaled budesonide in reducing risk of hospitalization and the need for systemic corticosteroids among children with acute moderate-to-severe asthma exacerbation.The findings of this meta-analysis support the use of inhaled budesonide in reducing risk of hospitalization and the need for systemic corticosteroids among children with acute moderate-to-severe asthma exacerbation.

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