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partnership, including the human-animal bond, will help inform the guide dog industry of how best to support their clients during this time and when transitioning to another dog. Findings may be applied to other service/assistance dog users and the pet owning community.Heart failure with preserved ejection fraction (HFpEF) is a major public health problem with growing prevalence and poor outcomes, mainly due to the lack of an effective treatment. HFpEF pathophysiology is heterogeneous and complex. Recently a "new paradigm" has been proposed, suggesting that cardiovascular and non-cardiovascular coexisting comorbidities lead to a systemic inflammatory state, perturbing the physiology of the endothelium and the perivascular environment and engaging molecular pathways that ultimately converge to myocardial fibrosis. If inflammation and fibrosis are the "fil rouge" in the heterogeneous spectrum of HFpEF, anti-fibrotic and anti-inflammatory drugs may have a role in its treatment. Pirfenidone is an orally bioavailable drug with antifibrotic and anti-inflammatory properties already approved for the treatment of idiopathic pulmonary fibrosis. Pirfenidone has been recently tested in animal models of myocardial fibrosis with promising results. Here we will review the rationale underlying the potential therapeutic effect of Pirfenidone in HFpEF.Background Endothelial cells (ECs) play a critical role in the maintenance of vascular homeostasis and in heart function. It was shown that activated fibroblast-derived exosomes impair cardiomyocyte function in hypertrophic heart, but their effect on ECs is not yet clear. Thus, we hypothesized that activated cardiac fibroblast-derived exosomes (FB-Exo) mediate EC dysfunction, and therefore modulation of FB-exosomal contents may improve endothelial function. Methods and Results Exosomes were isolated from cardiac fibroblast (FB)-conditioned media and characterized by nanoparticle tracking analysis and electron microscopy. ECs were isolated from mouse heart. ECs were treated with exosomes isolated from FB-conditioned media, following FB culture with TGF-β1 (TGF-β1-FB-Exo) or PBS (control) treatment. TGF-β1 significantly activated fibroblasts as shown by increase in collagen type1 α1 (COL1α1), periostin (POSTN), and fibronectin (FN1) gene expression and increase in Smad2/3 and p38 phosphorylation. Impaired endothelial cell function (as characterized by a decrease in tube formation and cell migration along with reduced VEGF-A, Hif1α, CD31, and angiopoietin1 gene expression) was observed in TGF-β1-FB-Exo treated cells. Furthermore, TGF-β1-FB-Exo treated ECs showed reduced cell proliferation and increased apoptosis as compared to control cells. TGF-β1-FB-Exo cargo analysis revealed an alteration in fibrosis-associated miRNAs, including a significant increase in miR-200a-3p level. Interestingly, miR-200a-3p inhibition in activated FBs, alleviated TGF-β1-FB-Exo-mediated endothelial dysfunction. Conclusions Taken together, this study demonstrates an important role of miR-200a-3p enriched within activated fibroblast-derived exosomes on endothelial cell biology and function.Objective To determine the effect of renal artery stenosis (RAS) resulting from acute type B aortic dissection (ATBAD) with thoracic endovascular aortic repair (TEVAR) on early prognosis in patients with ATBAD. Methods A total of 129 ATBAD patients in the National Acute Aortic Syndrome Database (AASCN) who underwent TEVAR between 2019 and 2020 were enrolled in our study. Patients were divided into two groups the RAS group and the non-RAS group. Results There were 21 RAS patients (16.3%) and 108 non-RAS patients (83.7%) in our cohort. No patient in our cohort died during the 1-month follow-up. There was no significant difference in preoperative creatinine clearance rate (CCr) between the two groups (90.6 ± 46.1 μmol/L in the RAS group vs. 78.7 ± 39.2 μmol/L in the non-RAS group, P = 0.303) but the RAS group had a significantly lower estimated glomerular filtration rate (eGFR) than the non-RAS group (83.3 ± 25.0 vs. 101.9 ± 26.9 ml/min, respectively; P = 0.028).One month after TEVAR, CCr was significantly higher (99.0 ± 68.1 vs. 78.5 ± 25.8 ml/min, P = 0.043) and eGFR (81.7 ± 23.8 vs. 96.0 ± 20.0 ml/min, P = 0.017) was significantly lower in the RAS group than in the non-RAS group. Conclusions In ATBAD, RAS could result in acute kidney injury (AKI) in the early stage after TEVAR. The RAS group had a high incidence of hypertension. These results suggest that patients with RAS may need further treatment.Epicardial adipose tissue (EAT) is correlated with endothelial dysfunction, metabolic syndrome, increased mortality and recent studies showed a possible association with the increased risk of stroke. We performed a systematic review of studies evaluating the association between EAT and stroke. Eighty studies met the inclusion criteria and were consequently analyzed. The review had Five main findings. First, the increased epicardial fat thickness (EFT) may be associated with the stroke episode. Second, regardless of the imaging method (echocardiography, MRI, and CT) this association remains. ICG-001 mw Third, the association of metabolic syndrome and atrial fibrillation seems to increase the risk of stroke. Fourth, this systematic review was considered as low risk of bias. Despite being unable to establish a clear association between EAT and stroke, we have organized and assessed all the research papers on this topic, analyzing their limitations, suggesting improvements in future pieces of research and pointing out gaps in the literature. Furthermore, the mechanistic links between increased EAT and stroke incidence remains unclear, thus, further research is warranted.Contemporary surgical and transcatheter aortic valve interventions offer effective therapy for a broad range of patients with severe symptomatic aortic valve disease. Both approaches have seen significant advances in recent years. Guidelines have previously emphasized 'surgical risk' in the decision between surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR), although this delineation becomes increasingly obsolete with more evidence on the effectiveness of TAVR in low surgical risk candidates. More importantly, decisions in tailoring aortic valve interventions should be patient-centered, accounting not only for operative risk, but also anatomy, lifetime management and specific co-morbidities. Aspects to be considered in a patient-tailored aortic valve intervention are discussed in this article.