Search

Potent P2Y12 receptor antagonists have been used widely for patients undergoing percutaneous coronary intervention with different results. Benefits from different regimens various between trials. Randomized controlled trials (RCTs) have restrictive inclusion and exclusion criteria; thus, they may limit the generalizability of the findings to a broader population. This study was aimed to comprehensively investigate the outcomes of potent P2Y12 inhibitors in patients undergoing PCI, including RCTs and real-world evidence (RWE) studies.Multiple electronic databases were systemically reviewed and searched on compared potent P2Y12 inhibitors with clopidogrel. The primary efficacy end point was composite ischemic cardiovascular event and primary safety endpoint was major bleeding. Overall estimates of proportions and incidence rates with 95 % confidence intervals (CI) were calculated using fixed-effects models. Total 24 studies (140,986 patients) underwent coronary intervention were included in this meta-analysis, including 18 RCTs and 6 large cohort studies with propensity score matching. The potent P2Y12 inhibitors including cangrelor, prasugrel, and ticagrelor, significantly decreased the risk of composite adverse cardiovascular ischemic events (95 % CI 0.89–0.96, p

Background: Although teachers of English are required to assess students' speaking proficiency in the Common European Framework of Reference for Languages (CEFR), their ability to rate is seldom evaluated. The application of descriptors in the assessment of English speaking on CEFR in the context of English as a foreign language has not often been investigated, either. Methods: The present study first introduced a form of rater standardization training. Two trained raters then assessed the speaking proficiency of 100 learners by means of actual corpus data. The study then compared their rating results to evaluate inter-rater reliability. Next, ten samples of exact/adjacent agreement between Raters 1 and 2 were rated by six teachers of English in tertiary education. Two of them had attended rater standardization training with Raters 1 and 2, while the other four had not received any relevant training. Results: The two raters agreed exactly in 44% of cases. The rating results between the two trained raters were closely correlated ([rho] = 0.893). Cross-tabulation showed that in one third of the samples, Rater 2 scored higher than Rater 1 and they agreed more often at the higher levels. The better rating performance of Teachers 1 and 2 suggested that rater standardization training may have helped enhance their performance. The unsatisfactory proportion of correctly assigned levels in teachers' ratings overall was probably due to the high input of subjective judgment based on vague CEFR descriptors. Conclusions: Regarding assessment, it is shown that the attendance of rater standardization training is of help in assessing learners' speaking proficiency in CEFR. This study provides a model for assessing data from spoken learner corpora, which adds an important attribute to future studies of learner corpora. The paper also raises doubts about teachers' ability to evaluate students' speaking proficiency in CEFR. As CEFR has been widely adopted in the relevant fields of English language teaching and assessment, it is suggested that the rating training framework established in this study, which uses learner corpus data, be offered to (prospective) teachers of English in tertiary education.

Atrial fibrillation (AF), characterized by structural remodeling involving atrial myocardial degradation and fibrosis, is linked with obesity and transforming growth factor beta 1 (TGF-β1). Aldehyde dehydrogenase 2 (ALDH2) deficiency, highly prevalent in East Asian people, is paradoxically associated with a lower AF risk. This study investigated the impact of ALDH2 deficiency on diet-induced obesity and AF vulnerability in mice, exploring potential compensatory upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme-oxygenase 1 (HO-1). Wild-type (WT) and ALDH2*2 knock-in (KI) mice were administered a high-fat diet (HFD) for 16 weeks. Despite heightened levels of reactive oxygen species (ROS) post HFD, the ALDH2*2 KI mice did not exhibit a greater propensity for AF compared to the WT controls. The ALDH2*2 KI mice showed equivalent myofibril degradation in cardiomyocytes compared to WT after chronic HFD consumption, indicating suppressed ALDH2 production in the WT mice. Atrial fibrosis did not proportionally increase with TGF-β1 expression in ALDH2*2 KI mice, suggesting compensatory upregulation of the Nrf2 and HO-1 pathway, attenuating fibrosis. In summary, ALDH2 deficiency did not heighten AF susceptibility in obesity, highlighting Nrf2/HO-1 pathway activation as an adaptive mechanism. Despite limitations, these findings reveal a complex molecular interplay, providing insights into the paradoxical AF–ALDH2 relationship in the setting of obesity. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor α (PPARα) plays a role in the pathogenesis of cardiac hypertrophy, although its underlying mechanism remains unclear. The purpose of this study was to evaluate the effect of PPARα activation on endothelin-1- (ET-1-) caused cardiomyocyte hypertrophy and explore its underlying mechanisms. Human cardiomyocytes (HCMs) were cultured with or without ET-1, whereafter the inhibitory effects of fenofibrate, a PPARα activator, on cell size and adiponectin protein were tested. We examined the activation of extracellular signal-regulated kinase (ERK) and p38 proteins caused by ET-1 and the inhibition of the ERK and p38 pathways on ET-1-induced cell size and adiponectin expression. Moreover, we investigated the interaction of PPARα with adiponectin and nuclear factor-κB (NF-κB) by electrophoretic mobility shift assays and coimmunoprecipitation. ET-1 treatment significantly increased cell size, suppressed PPARα expression, and enhanced the expression of adiponectin. Pretreatment with fenofibrate inhibited the increase in cell size and enhancement of adiponectin expression. ET-1 significantly activated the ERK and p38 pathways, whereas PD98059 and SB205380, respectively, inhibited them. Our results suggest that activated PPARα can decrease activation of adiponectin and NF-κB and inhibit ET-1-induced cardiomyocyte hypertrophy.