Association Between Regulatory T Cells and Ischemic Heart Disease: a Mendelian Randomization Study

BACKGROUND: An imbalance of innate and acquired immune responses is significantly involved in the pathophysiology of coronary atherosclerosis and the occurrence of ischemic heart disease (IHD). Regulatory T cells (Tregs) play an essential regulatory role in atherosclerotic plaque formation and maintenance; therefore, dysfunction of Tregs triggers the formation of atherosclerotic plaques and accelerates their progression. However, due to the inherent limitations of observational research, clinical evidence is limited concerning the relationship between the variation in peripheral Tregs and the risk of IHD, and the cause-and-effect relationship between these factors is unclear. Mendelian randomization (MR) uses genetic variation as a proxy for exposure and can be used to inferentially determine the causal effect of exposure on outcomes. We thus used MR analysis to investigate whether there is a causal relationship between the biomarkers of Tregs and IHD. METHODS: Selected genetic variants (P RESULTS: We identified a set of 197 single-nucleotide polymorphisms (SNPs) that served as instrumental variables (IVs) for evaluating 51 Treg subtypes. Thirteen significant variables were found to be potentially associated with IHD. After false-discovery rate (FDR) adjustment, we identified four Treg subtypes to be causally protective for IHD risk: CD28 on activated & secreting CD4 Tregs [odds ratio (OR) =0.89; 95% confidence interval (CI): 0.82-0.96; P=3.10E-03; adjusted P=0.04], CD28 on activated CD4 Tregs (OR =0.87; 95% CI: 0.80-0.95; P=3.10E-03; adjusted P=0.04), CD28 on CD4 Tregs (OR =0.87; 95% CI: 0.80-0.96; P=3.41E-03; adjusted P=0.04), and CD28 on resting CD4 Treg cell (OR =0.91; 95% CI: 0.85-0.97; P=3.48E-03; adjusted P=0.04). Reverse MR analysis found eight potential causal variables, but these associations were nonsignificant after FDR correction (all adjusted P values \u3e0.05). CONCLUSIONS: This study identified the significance of elevated CD28 expression on CD4 Tregs as a novel molecular modifier that may influence IHD occurrence, suggesting that targeting CD28 expression on CD4 Tregs could offer a promising therapeutic approach for IHD

Cortico-amygdalar connectivity and externalizing/internalizing behavior in children with neurodevelopmental disorders

Background: Externalizing and internalizing behaviors contribute to clinical impairment in children with neurodevelopmental disorders (NDDs). Although associations between externalizing or internalizing behaviors and cortico-amygdalar connectivity have been found in clinical and non-clinical pediatric samples, no previous study has examined whether similar shared associations are present across children with different NDDs. Methods: Multi-modal neuroimaging and behavioral data from the Province of Ontario Neurodevelopmental Disorders (POND) Network were used. POND participants aged 6–18 years with a primary diagnosis of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) or obsessive–compulsive disorder (OCD), as well as typically developing children (TDC) with T1-weighted, resting-state fMRI or diffusion weighted imaging (DWI) and parent-report Child Behavioral Checklist (CBCL) data available, were analyzed (total n = 346). Associations between externalizing or internalizing behavior and cortico-amygdalar structural and functional connectivity indices were examined using linear regressions, controlling for age, gender, and image-modality specific covariates. Behavior-by-diagnosis interaction effects were also examined. Results: No significant linear associations (or diagnosis-by-behavior interaction effects) were found between CBCL-measured externalizing or internalizing behaviors and any of the connectivity indices examined. Post-hoc bootstrapping analyses indicated stability and reliability of these null results. Conclusions: The current study provides evidence towards an absence of a shared linear relationship between internalizing or externalizing behaviors and cortico-amygdalar connectivity properties across a transdiagnostic sample of children with different primary NDD diagnoses and TDC. Different methodological approaches, including incorporation of multi-dimensional behavioral data (e.g., task-based fMRI) or clustering approaches may be needed to clarify complex brain-behavior relationships relevant to externalizing/internalizing behaviors in heterogeneous clinical NDD populations

Assessment of the impact of intravenous antibiotics treatment on gut microbiota in patients: Clinical data from pre-and post-cardiac surgery

Background and aimsSurgical site infection is a common complication after surgery. Periprocedural antibiotics are necessary to prescribe for preventing or treating infections. The present study aimed to explore the effect of intravenous antibiotics on gut microbiota and menaquinone biosynthesis in patients, especially in elderly patients undergoing cardiac surgery.MethodsA total of 388 fecal samples were collected from 154 cardiac surgery patients. The V3–V4 hypervariable region of the bacterial 16S rRNA gene was amplified and sequenced on a MiSeq PE300. The gut microbiota diversity of samples was analyzed in terms of α- and β-diversity at the OTU level. The different groups were classified according to antibiotics in combinations and single antibiotics. PICRUSt2 was used for preliminary prediction of the gut microbiota function for menaquinone biosynthesis.ResultsThe intravenously administered antibiotics which are excreted via bile represents the main antibiotics that could disturb the gut microbiota’s composition in cardiac surgery patients, especially for elderly patients. The effect of antibiotics on gut microbiota is produced after antibiotics treatments over one week. The recovery of gut microbiota to the state of pre-antibiotics may require over two weeks of antibiotics withdrawal. Sex factor doesn’t represent as an influencer in gut microbiota composition. Long-term use of cefoperazone-sulbactam may affect coagulation function.ConclusionsThe composition of the gut microbiota had a significant change post-intravenous antibiotics treatment in cardiac surgery patients. The richness and diversity of gut microbiota are increased in elderly patients

Criteria for determining the need for surgical treatment of tricuspid regurgitation during mitral valve replacement

<p>Abstract</p> <p>Background</p> <p>Tricuspid regurgitation (TR) is common in patients with mitral valve disease; however, there are no straightforward, rapidly determinably criteria available for deciding whether TR repair should be performed during mitral valve replacement. The aim of our retrospective study was to identify a simple and fast criterion for determining whether TR repair should be performed in patients undergoing mitral valve replacement.</p> <p>Methods</p> <p>We reviewed the records of patients who underwent mitral valve replacement with or without (control) TR repair (DeVega or Kay procedure) from January 2005 to December 2008. Preoperative and 2-year postoperative echocardiographic measurements included right ventricular and atrial diameter, interventricular septum size, TR severity, ejection fraction, and pulmonary artery pressure.</p> <p>Results</p> <p>A total of 89 patients were included (control, n = 50; DeVega, n = 27; Kay, n = 12). Demographic and clinical characteristics were similar between groups. Cardiac variables were similar between the DeVega and Kay groups. Right atrium and ventricular diameter and ejection fraction were significantly decreased postoperatively both in the control and operation (DeVega + Kay) group (<it>P </it>< 0.05). Pulmonary artery pressure was significantly decreased postoperatively in-operation groups (<it>P </it>< 0.05). Our findings indicate that surgical intervention for TR should be considered during mitral valve replacement if any of the following preoperative criteria are met: right atrial transverse diameter > 57 mm; right ventricular end-diastolic diameter > 55 mm; pulmonary artery pressure > 58 mmHg.</p> <p>Conclusions</p> <p>Our findings suggest echocardiography may be used as a rapid and simple means of determining which patients require TR repair during mitral valve replacement.</p

A study of data-driven momentum and disposition effects in the Chinese stock market by functional data analysis

We apply a functional data analysis approach to decompose the cross-sectional Fama–French three-factor model residuals in the Chinese stock market. Our results indicate that other than Fama–French three factors, there are two orthonormal asset pricing factors describing the behavioral biases in their historical performances: between winner and loser stocks, and extreme and mediocre-performing stocks, respectively. We explain these two factors through investors’ overreaction, overconfidence and the lead-lag effect. These findings empirically show the existence of momentum and disposition effects in the Chinese stock market. A buy-and-hold mean-variance optimized portfolio incorporating these two market anomalies boosts the Sharpe ratio to 1.27

Mesenchymal Stem Cells for Cardiac Regenerative Therapy: Optimization of Cell Differentiation Strategy

With the high mortality rate, coronary heart disease (CHD) has currently become a major life-threatening disease. The main pathological change of myocardial infarction (MI) is the induction of myocardial necrosis in infarction area which finally causes heart failure. Conventional treatments cannot regenerate the functional cell efficiently. Recent researches suggest that mesenchymal stem cells (MSCs) are able to differentiate into multiple lineages, including cardiomyocyte-like cells in vitro and in vivo, and they have been used for the treatment of MI to repair the injured myocardium and improve cardiac function. In this review, we will focus on the recent progress on MSCs derived cardiomyocytes for cardiac regeneration after MI