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BACKGROUND Diffusely abnormal white matter (DAWM) regions are observed in magnetic resonance images of secondary progressive multiple sclerosis (SPMS) patients. However, their role in clinical progression is still not established. OBJECTIVES To characterize the longitudinal volumetric and intensity evolution of DAWM and focal white matter lesions (FWML) and assess their associations with clinical outcomes and progression in SPMS. METHODS Data include 589 SPMS participants followed up for 3 years (3951 time points). FWML and DAWM were automatically segmented. Screening DAWM volumes that transformed into FWML at the last visit (DAWM-to-FWML) and normalized T1-weighted intensities (indicating severity of damage) in those voxels were calculated. RESULTS FWML volume increased and DAWM volume decreased with an increase in disease duration (p less then 0.001). The Expanded Disability Status Scale (EDSS) was positively associated with FWML volumes (p = 0.002), but not with DAWM. DAWM-to-FWML volume was higher in patients who progressed (2.75 cm3 vs. 1.70 cm3; p less then 0.0001). Normalized T1-weighted intensity of DAWM-to-FWML was negatively associated with progression (p less then 0.00001). CONCLUSION DAWM transformed into FWML over time, and this transformation was associated with clinical progression. DAWM-to-FWML voxels had greater normalized T1-weighted intensity decrease over time, in keeping with relatively greater tissue damage. Evaluation of DAWM in progressive multiple sclerosis provides a useful measure for therapies aiming to protect this at-risk tissue with the potential to slow progression.DNA methylation is dynamic, varies throughout the life course, and its levels are influenced by lifestyle and environmental factors, as well as by genetic variation. The leading genetic variants at stroke risk loci identified to date explain roughly 1-2% of stroke heritability. Most of these single nucleotide polymorphisms are situated within a regulatory sequence marked by DNase I hypersensitivity sites, which would indicate involvement of an epigenetic mechanism. To detect epigenetic variants associated with stroke occurrence and stroke subtypes.A two-stage case-control epigenome-wide association study was designed. The discovery sample with 401 samples included 218 ischaemic stroke (IS) patients, assessed at Hospital del Mar (Barcelona, Spain) and 183 controls from the REGICOR cohort. In two independent samples (N = 226 and N = 166), we replicated 22 CpG sites differentially methylated in IS in 21 loci, including 2 CpGs in locus ZFHX3, which includes known genetic variants associated with stroke. The pathways associated with these loci are inflammation and angiogenesis. The meta-analysis identified 384 differentially methylated CpGs, including loci of known stroke and vascular risk genetic variants, enriched by loci involved in lipid metabolism, adipogenesis, circadian clock, and glycolysis pathways.We identified a set of 22 CpGs in 21 loci associated with IS. Our analysis suggests that DNA methylation changes may contribute to orchestrating gene expression that contributes to IS.BACKGROUND Environmental factors are associated with acquiring multiple sclerosis (MS) particularly in adolescence. OBJECTIVE To test for association between MS and exposure to passive smoking at the age of 10-19. METHODS A total of 919 patients from the Danish MS Registry and Biobank and 3419 healthy blood donors who had not smoked before the age of 19 were targeted. We analyzed separately for each sex and for those never-smokers (cohort 1) and active smokers above the age of 19 (cohort 2). https://www.selleckchem.com/products/bay80-6946.html All participants completed standardized questionnaires about smoking and lifestyle. We matched cases and controls in the ratio of 12 by propensity scores discarding unmatchable individuals and used logistic regression adjusted for all covariates and interactions. RESULTS After matching, we included 110/213 male cases/controls and 232/377 female case/controls in cohort 1. In cohort 2, the numbers were 160/320 and 417/760, respectively. Among women in cohort 1, the odds ratio (OR) for MS by passive smoking at the age of 10-19 was 1.432 (p = 0.037) but in men it was 1.232 (p = 0.39). Among men in cohort 2, OR was 1.593 (p = 0.022) but among women it was only 1.102 (p = 0.44). CONCLUSION Among never smokers, female MS cases were more often than female controls reported with passive smoking between the age of 10 and 19, and among smokers above the age of 19, male MS patients were more often than male controls reported with passive smoking.The long-armed scarab (Cheirotonus gestroi) is an endangered large insect in southwestern China and neighboring countries; however, limited information is available regarding its population genetics, hindering conservation efforts. Therefore, we investigated the population genetic structure and evolutionary history of C. gestroi in southwestern China. Twenty-five haplotypes were obtained from 47 specimens across five populations. The Dawei Mountain (DWS) population differed from other populations by a high genetic distance. Population structure analysis generated three distinct clades, corresponding to Hengduan Mountains (HM), Ailao Mountains (AM), and Dawei Mountains (DM), and high-level genetic diversity was found in two HM populations. Collectively, the strong genetic differentiation among populations might be due to limited gene flow, geographical isolation, and habitat fragmentation. Therefore, while developing a conservation strategy, HM, AM, and DM groups should be defined as separate management units. Additionally, the DWS population should be given priority protection due to its uniqueness and low genetic diversity.The aim of this study was to assess outcomes from a multilevel social network intervention to promote the health of Black men. Through a community-academic collaboration and using a participatory research approach, we implemented the intervention over 4 years in a 110-block area of an urban neighborhood. The project aimed to implement a neighborhood peer outreach and leadership network to strengthen social support of Black men and increase community and family engagement. Intervention activities included three 12-month intergenerational peer support groups (N = 46), a door-to-door outreach campaign (N = 186), media and communication efforts, and a community partner network. Primary outcomes for the peer support groups were measured using a pretest/posttest cohort design and included social support, perceived stress, social capital, and global self-esteem. Primary outcomes for the door-to-door outreach campaign were measured using a repeated cross-sectional design and included a sense of community, neighborhood social interaction, perceived neighborhood control, and self-rated health status.
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