actors suggested greater importance of hypertension, diabetes, and central adiposity in South Asian individuals. Within a large prospective study, South Asian individuals had substantially higher risk of atherosclerotic cardiovascular disease compared with individuals of European ancestry, and this risk was not captured by the Pooled Cohort Equations.Within a large prospective study, South Asian individuals had substantially higher risk of atherosclerotic cardiovascular disease compared with individuals of European ancestry, and this risk was not captured by the Pooled Cohort Equations.Rationale Phosphodiesterase-5 (PDE5) inhibition reduces the occurrence of ventricular arrhythmias following myocardial ischemia. However, the mechanisms of the anti-arrhythmic effects of PDE5 inhibition are unknown. Diastolic calcium (Ca2+) waves lead to arrhythmias by inducing delayed after-depolarizations. Ca2+ waves are initiated when sarcoplasmic reticulum (SR) Ca2+ content reaches a threshold level and the SR releases Ca2+ spontaneously and generates a depolarizing inward sodium-calcium exchange (NCX) current. Objective To determine the effects of PDE5 inhibition on the propensity for ventricular arrhythmias in a pro-arrhythmic large animal model and establish the role of alterations of intracellular Ca2+ cycling / SR Ca2+ content. Methods and Results Arrhythmia burden, monophasic action potentials and beat-to-beat variability of repolarization were measured in a sheep model using the IKr inhibitor dofetilide to induce QT prolongation and arrhythmia. Ca2+ transients, Ca2+ waves and SR Ca2+ content were m+ content and are PKG-dependent.Background The etiology of life-threatening cardiopulmonary diseases such as Pulmonary Hypertension (PH) and Chronic Obstructive Pulmonary Disease (COPD) originates from a complex interplay of environmental factors and genetic predispositions, which is not fully understood. Likewise, little is known about developmental abnormalities or epigenetic dysregulations that might predispose for PH or COPD in adult individuals. Methods To identify pathology-associated epigenetic alteration in diseased lung tissues, we screened a cohort of human PH and COPD patients for changes of histone modifications by immunofluorescence staining. To analyze the function of H4K20me2/3 in lung pathogenesis, we developed a series of Suv4-20h1 knockout mouse lines targeting cardiopulmonary progenitor cells (CPPs) and different heart and lung cell types, followed by hemodynamic studies and morphometric assessment of tissue samples. selleckchem Molecular, cellular and biochemical techniques were applied to analyze the function of Suv4-20h1-dependent4-20H1 in cardiopulmonary co-development and uncover developmental origins of cardiopulmonary diseases. We assume that the study will facilitate the understanding of pathogenic events causing PH and COPD, and aid the development of epigenetic drugs for treatment of cardiopulmonary diseases. We studied the outcomes of hip and knee arthroplasties in a high-volume arthroplasty centre to determine if patients with morbid obesity (BMI ≥ 40 kg/m ) had unacceptably worse outcomes as compared to those with BMI < 40 kg/m . In a two-year period, 4,711 patients had either total hip arthroplasty (THA; n = 2,370), total knee arthroplasty (TKA; n = 2,109), or unicompartmental knee arthroplasty (UKA; n = 232). Of these patients, 392 (8.3%) had morbid obesity. We compared duration of operation, anaesthetic time, length of stay (LOS), LOS > three days, out of hours attendance, emergency department attendance, readmission to hospital, return to theatre, and venous thromboembolism up to 90 days. Readmission for wound infection was recorded to one year. Oxford scores were recorded preoperatively and at one year postoperatively. On average, the morbidly obese had longer operating times (63 vs 58 minutes), longer anaesthetic times (31 vs 28 minutes), increased LOS (3.7 vs 3.5 days), and significantly more readmissions for wound infection (1.0% vs 0.3%). There were no statistically significant differences in either suspected or confirmed venous thromboembolism. Improvement in Oxford scores were equivalent. Although morbidly obese patients had less favourable outcomes, we do not feel that the magnitude of difference is clinically significant when applied to an individual, particularly when improvement in Oxford scores were unrelated to BMI. Cite this article 2021;2(7)515-521.Although morbidly obese patients had less favourable outcomes, we do not feel that the magnitude of difference is clinically significant when applied to an individual, particularly when improvement in Oxford scores were unrelated to BMI. Cite this article Bone Jt Open 2021;2(7)515-521. There are various reports of air leaks with coronavirus disease 2019 (COVID-19). We undertook a systematic review of all published case reports and series to analyse the types of air leaks in COVID-19 and their outcomes. The literature search from PubMed, Science Direct, and Google Scholar databases was performed from the start of the pandemic till 31 March 2021. The inclusion criteria were case reports or series on (1) laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, (2) with the individual patient details, and (3) reported diagnosis of one or more air leak syndrome (pneumothorax, subcutaneous emphysema, pneumomediastinum, pneumoperitoneum, pneumopericardium). A total of 105 studies with 188 patients were included in the final analysis. The median age was 56.02 (SD 15.53) years, 80% males, 11% had previous respiratory disease, and 8% were smokers. Severe or critical COVID-19 was present in 50.6% of the patients. Pneumothorax (68%) was the most common type of entilation and escalation of respiratory support. Peripartum cardiomyopathy (PPCM) is a life-threatening disease in women without previously known cardiovascular disease. It is characterized by a sudden onset of heart failure before or after delivery. Previous studies revealed that the generation of a 16-kDa PRL (prolactin) metabolite, the subsequent upregulation of miR-146a, and the downregulation of the target gene is a common driving factor of PPCM. miRNA profiling was performed in plasma of PPCM patients (n=33) and postpartum-matched healthy CTRLs (controls; n=36). Elevated miRNAs in PPCM plasma, potentially targeting ERBB4 (erythroblastic leukemia viral oncogene homolog 4), were overexpressed in cardiomyocytes using lentiviral vectors. Next, cardiac function, cardiac morphology, and PPCM phenotype were investigated after recurrent pregnancies of HZ (heterozygous) cardiomyocyte-specific mice ( , n=9) with their age-matched nonpregnant CTRLs (n=9-10). Here, we identify 9 additional highly conserved miRNAs (miR-199a-5p and miR-199a-3p, miR-145a-5p, miR-130a-3p, miR-135a-5p, miR-221-3p, miR-222-3p, miR-23a-3p, and miR19b-3p) that target tyrosine kinase receptor ERBB4 and are over 4-fold upregulated in plasma of PPCM patients at the time of diagnosis.