Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta?=??0.0264, p value?=?3.5?×?10–8) in the discovery panel and was replicated in replication panel (beta?=??0.07, p value?=?0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value?=?1.4?×?10–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.
Our objectives were to assess sperm alteration and adipose tissue (AT) genes expression related to steroid metabolism subsequent to fatty acids consumption. Twenty‐nine mature male mice were divided into: fat diet (FD; n = 15) and the control group (n = 14). FD group was fed with low level of trans and saturated fatty acids source for 60 days. Sperm parameters, levels of hormones and the mRNA abundance of the target genes in AT were assessed. The sperm concentration, total and progressive motilities were lower in FD group compared to that of control (p < 0.01). Blood estradiol levels increased in FD (p < 0.001), whereas no significant difference was observed in testosterone. The mRNA levels of StAR, CYP11A1, CYP17A1, 17βHSD7 and 17βHSD12 in AT of FD were higher than those of the control (p < 0.05). In contrast, mRNA level of Cyp19a1 in FD was significantly (p < 0.05) lower than that of control. 17βHSD12 and 17βHSD7 (as oestrogenic genes) increased, while 17βHSD5 and 17βHSD3 (as androgenic genes) remained unchanged, indicating that dietary trans/saturated fatty acids affect AT genes expression. Probably, sperm parameters were altered by increment of expression level of genes involved in oestrogenic metabolism rather than those engaged in androgenic metabolism after fatty acids consumption. 相似文献
Analyzing the structure and function of the brain from a network perspective has increased considerably over the past two decades, with regional subnetwork analyses becoming prominent in the recent literature. However, despite the fact that the brain, as a complex system of interacting subsystems (i.e., subnetworks), cannot be fully understood by analyzing its constituent parts as independent elements, most studies extract subnetworks from the whole and treat them as independent networks. This approach entails neglecting their interactions with other brain regions and precludes identifying potential compensatory mechanisms outside the analyzed subnetwork. In this study, using simulated and empirical data, we show that the analysis of brain subnetworks within the context of their whole‐brain networks, that is, including their interactions with other brain regions, can yield different outcomes when compared to analyzing them as independent networks. We also provide a multivariate mixed‐effects modeling framework that allows analyzing subnetworks within the context of their whole‐brain networks, and show that it can better disentangle global (whole‐brain) and local (subnetwork) differences when compared to standard t‐test analyses. T‐test analyses may produce misleading results in identifying complex global and local level differences. The provided multivariate model is an extension of a previously developed model for global, system‐level hypotheses about the brain. The modified version detailed here provides the same utilities as the original model—quantifying the relationship between phenotypes and brain connectivity, comparing brain networks among groups, predicting brain connectivity from phenotypes, and simulating brain networks—but for local, subnetwork‐level hypotheses. 相似文献
Preoperative embolisation is a commonly performed adjunct to microsurgical excision of brain arteriovenous malformations (bAVMs), with aims such as lessening the technical difficulty of the microsurgical procedure, reducing operative time, decreasing blood loss, and improving patient functional outcomes. We aim to perform a systematic review of randomised trials and cohort studies evaluating preoperative embolisation of bAVMs published between 01 January 2000 and 31 March 2021 and appraise its role in clinical practice. A MEDLINE search was performed, and articles reporting on outcomes following preoperative embolisation, as an adjunct to microsurgery, were eligible for inclusion. PRISMA reporting and Cochrane Handbook guidelines were followed. The primary outcome measure was the risk of complications associated with preoperative embolisation. The study was registered with PROSPERO (CRD42021244231). Of the 1661 citations, 8 studies with 588 patients met predefined inclusion criteria. No studies specifically compared outcomes of surgical excision of bAVMs between those with and without preoperative embolisation. Spetzler Martin (SM) grading was available in 301 cases. 123 of 298 (41?28%) patients presented with haemorrhage. Complications related to embolisation occurred in 175/588 patients (29.4%, 95% CI 19.6–40.2). Permanent neurological deficits occurred in 36/541 (6%, 95% CI 3.9–8.5) and mortality in 6/588 (0.41%, 95% CI 0–1.4). This is the first systematic review evaluating preoperative embolisation of bAVMs. Existing studies assessing this intervention are of poor quality. Associated complication rates are significant. Based on published literature, there is currently insufficient evidence to recommend preoperative embolisation of AVMs. Further studies are required to ascertain if there are benefits of this procedure and if so, in which cases.
There are likely to be differences in alcohol consumption levels and patterns across local areas within a country, yet survey data is often collected at the national or sub-national/regional level and is not representative for small geographic areas. This paper presents a method for reweighting national survey data—the Health Survey for England—by combining survey and routine data to produce simulated locally representative survey data and provide statistics of alcohol consumption for each Local Authority in England. We find a 2-fold difference in estimated mean alcohol consumption between the lightest and heaviest drinking Local Authorities, a 4.5-fold difference in abstention rates, and a 3.5-fold difference in harmful drinking. The method compares well to direct estimates from the data at regional level. The results have important policy implications in itself, but the reweighted data can also be used to model local policy effects. This method can also be used for other public health small area estimation where locally representative data are not available. 相似文献