Oxidized low-density lipoprotein-induced expression of ABCA1 in blood monocytes precedes coronary atherosclerosis and is associated with plaque complexity in hypercholesterolemic pigs

BACKGROUND: Elevated oxidized low-density lipoprotein (oxLDL) is associated with atherosclerosis and high cardiovascular risk. Previously, we identified 18 genes in coronary plaque macrophages of hypercholesterolemic pigs that correlated with plaque oxLDL. OBJECTIVE: To determine which of these genes were differentially expressed in blood monocytes and correlated with blood and plaque oxLDL and with plaque complexity. METHODS: RNA expression in monocytes of 27 hypercholesterolemic and 12 control pigs was analyzed with quantitative real-time polymerase chain reaction. RESULTS: Five of 12 genes with detectable expression in monocytes were overexpressed (at P < 0.01 level) in blood monocytes of hypercholesterolemic pigs: ABCA1, SCD, IRF1, SDC2, and TLR2. ABCA1 RNA expression in blood monocytes correlated with blood oxLDL, and its RNA and protein expression was increased prior to atherosclerotic plaque formation. Higher expression of ABCA1 in monocytes was associated with higher plaque complexity and higher plaque oxLDL. Immunostaining of coronary plaques showed the association of ABCA1 with macrophages, lipids, and oxLDL; ABCA1 protein correlated with plaque oxLDL (R(2) = 0.66; P < 0.0001). In THP-1 monocytes, oxLDL induced ABCA1 expression. OxLDL-induced foam cell generation in THP-1 and human monocyte-derived macrophages was associated with a further increase of ABCA1 expression. CONCLUSIONS: The increase of ABCA1 in monocytes in association with blood oxLDL prior to atherosclerotic lesion formation and the association of higher ABCA1 with higher plaque complexity suggests that ABCA1 is an early biomarker of atherosclerosis. Studies in humans are warranted.     

Clinical Results of Far‐Field R‐Wave Reduction with a Short Tip‐Ring Electrode

Background: Far‐field R‐wave (FFRW) sensing of the atrial lead of AAI or DDD pacemakers causes incorrect mode switches and remains a problem in patients with atrial arrhythmias in whom low voltage sensing is essential. We studied a pacing electrode with a short tip‐ring distance (1.1 mm). We compared our findings with recordings from a conventional electrode with a larger tip‐ring distance (10 mm). Methods: Thirty‐six consecutive patients with an indication for DDD pacing were implanted with the short tip‐ring electrode. Another 23 patients received the conventional electrode. FFRW and P‐wave amplitudes during pacing and intrinsic ventricular depolarization were measured at implantation. Measurements were repeated before hospital discharge and at follow‐up between 10 and 14 days after implantation. Results: P‐wave amplitude was slightly smaller in the short tip‐ring group (2.71 ± 1.04 vs 3.17 ± 1.30 mV in the conventional group, respectively, P = NS). All P‐waves exceeded 1.2 mV. FFRW during pacing was 0.07 ± 0.05 in the short tip‐ring group and 0.54 ± 0.32 mV in the conventional group (P < 0.001). FFRW during intrinsic rhythm was 0.08 ± 0.04 and 0.55 ± 0.31 mV, respectively (P < 0.001). The ratio between P‐wave and FFRW was 48.6 ± 27.2 in the short tip‐ring group and 7.3 ± 4.4 in the conventional group (P < 0.001). FFRW and P‐wave amplitudes did not change at hospital discharge or during follow‐up. Conclusion: FFRW can be suppressed without compromising P‐wave sensing by using a pacing electrode with a short tip‐ring distance. Whether reduced FFRW amplitude results in clinical endpoints remains to be determined.     

Selectin haplotypes and the risk of venous thrombosis: influence of linkage disequilibrium with the factor V Leiden mutation

Summary.  Background:  Selectins (E-, L- and P-selectin) and their most important counter-receptor P-selectin glycoprotein ligand (SELPLG) facilitate the interaction of platelets, leukocytes and endothelial cells at inflammatory sites. Selectin polymorphisms/haplotypes have been associated with cardiovascular disease. Objectives:  We investigated the association between haplotypes (H) of these four genes and deep venous thrombosis (DVT) risk. We additionally explored the effect of linkage disequilibrium (LD) with the nearby Factor V Leiden mutation (FVL). Furthermore, interactions between SELPLG polymorphisms and selectin polymorphisms were investigated. Patients/methods:  Leiden Thrombophilia Study (LETS) subjects were genotyped for 24 polymorphisms by Taq Man or PCR–RFLP, detecting all common haplotypes in four blocks. P-selectin was analyzed in two blocks, upstream (SELPup) and downstream (SELPdown) of the recombination hotspot. Results:  In E- and L-selectin, none of the haplotypes was associated with DVT risk. In SELPup, H2-carriers had a 1.3-fold increased risk (95% CI, 1.0–1.7), whereas H4-carriers had a 1.4-fold decreased risk (95% CI, 0.5–1.0). In SELPdown, H2-carriers had a 1.3-fold increased risk (95% CI, 1.0–1.7). Because of LD with FVL, we subsequently excluded all FVL-carriers and all risks disappeared. Mutual adjustment within a logistic regression model resulted in disappearance of the risks for the SELP haplotypes, whereas FVL risk remained. Conclusions:  After adjustment for LD with FVL, none of the selectin haplotypes was associated with DVT risk, showing that the increased risks of the selectin haplotypes were a reflection of the effect of FVL on thrombosis risk.     

美国教学医院教师专业发展的全国性调查

在当前医学教育持续变革的背景中,医学教师的专业发展成为广泛关注的焦点.为了解目前美国以提高教师的教学技能为目标的教师专业发展(faculty development,FD)活动的参与率、课程设计、教学方法和评估策略等情况,美国约翰·霍普金斯大学预防、流行病学和临床研究中心采取邮件调查的方式,对美国277家教学医院进行了调查.     

包虫病病原在我国的流行现状及成因分析

目的分析青海省甘德县2017—2019年包虫病的筛查情况及治疗效果,为当地包虫病进一步的防治工作提供依据。方法收集青海省甘德县2017—2019年包虫病筛查登记、包虫病临床治疗记录、包虫病患者社区管理记录等资料,统计分析筛查阳性率及治疗效果等。结果2017—2019年青海省甘德县包虫病筛查阳性率逐年降低,不同乡镇间包虫病筛查阳性率有差异。2017年上贡麻乡筛查阳性率最高,达2.719%,2018、2019年各乡镇包虫病筛查阳性率都控制在1%以下。2017—2019年甘德县包虫病治疗人数逐年减少,治疗死亡或无效病例也在减少,至2019年全县仅有1例死亡或无效病例。结论青海省甘德县包虫病筛查和治疗工作稳步推进,下阶段应重点关注漏检、漏治人群。