Activity

Construction workers are exposed to a mixture of substances in the workplace considered carcinogenic. This study aimed to characterise gene-specific changes in DNA methylation over the workweek in this population as this type of environmental exposure has not been studied extensively.

We evaluated their DNA methylation in 4 gene-promoter regions (

and

) and 2 repeat elements (

and

) in blood samples obtained on the first and fifth day of the same workweek of a group of 39 male construction workers. DNA methylation was measured by bisulphite-PCR-Pyrosequencing. We also measured the levels of trace elements in the whole blood by ICP-MS.

Only the

gene had significant differences in the average methylation level between the first and fifth day of the workweek. We also observed that the levels of Cu, Pb, Se, Mn, and Ti decreased during the fifth day of exposure, and only lead, titanium and copper showed a low significant correlation with the methylation level mean for three specific CpG sites of the

.

In summary, the data suggest that altered levels of

methylation in construction workers may be a potential biomarker of recent exposure in this environment.

In summary, the data suggest that altered levels of CDKN2A methylation in construction workers may be a potential biomarker of recent exposure in this environment.Background Among older patients with atrial fibrillation, there are limited data examining clinically meaningful changes in quality of life (QoL). We examined the extent of, and factors associated with, clinically meaningful change in QoL over 1-year among older adults with atrial fibrillation. Methods and Results Patients from cardiology, electrophysiology, and primary care clinics in Massachusetts and Georgia were enrolled in a cohort study (2015-2018). The Atrial Fibrillation Effect on Quality-of-Life questionnaire was used to assess overall QoL and across 3 subscales symptoms, daily activities, and treatment concern. learn more Clinically meaningful change in QoL (ie, difference between 1-year and baseline QoL score) was categorized as either a decline (≤-5.0 points), no clinically meaningful change (-5.0 to +5.0 points), or an increase (≥+5.0 points). Ordinal logistic models were used to examine factors associated with QoL changes. Participants (n=1097) were on average 75 years old, 48% were women, and 87% White. Approximately 40% experienced a clinically meaningful increase in QoL and 1 in every 5 patients experienced a decline in QoL. After multivariable adjustment, women, non-Whites, those who reported depressive and anxiety symptoms, fair/poor self-rated health, low social support, heart failure, or diabetes mellitus experienced clinically meaningful declines in QoL. Conclusions These findings provide insights to the magnitude of, and factors associated with, clinically meaningful change in QoL among older patients with atrial fibrillation. Assessment of comorbidities and psychosocial factors may help identify patients at high risk for declining QoL and those who require additional surveillance to maximize important clinical and patient-centered outcomes.Background Vascular calcification (VC) is associated with high morbidity and mortality among older adults, a population that exhibits a higher tendency for developing frailty at the same time. Whether VC serves as a risk factor for the development of frailty in this population remains unclear. Methods and Results We analyzed a prospectively assembled cohort of community-dwelling older adults between 2014 and 2017 (n=1783). Frailty and prefrailty were determined on the basis of the Study of Osteoporotic Fractures criteria, and VC was measured using semiquantitative aortic arch calcification (AAC) and abdominal aortic calcification scoring. We conducted multiple logistic regression with prefrailty or frailty as the dependent variable, incorporating sociodemographic profiles, comorbidities, medications, laboratory data, AAC status/severity, and other geriatric phenotypes. Among all participants, 327 (18.3%) exhibited either prefrailty (15.3%) or frailty (3.1%), and 648 (36.3%) exhibited AAC. After adjusting for multiple confounders, we found that AAC incidence was associated with a substantially higher probability of prefrailty or frailty (odds ratio [OR], 11.9; 95% CI, 7.9-15.4), with a dose-responsive relationship (OR for older adults with AAC categories 1, 2, and 3 was 9.3, 13.6, and 52.5, respectively). Similar association was observed for older adults with abdominal aortic calcification (OR, 5.0; 95% CI, 1.3-19.5), and might be replicable in another cohort of patients with end-stage renal disease. Conclusions Severity of VC exhibited a linear positive relationship with frailty in older adults. Our findings suggest that a prompt diagnosis and potential management of VC may assist in risk mitigation for patients with frailty.Background Assessment of atherosclerotic cardiovascular disease (ASCVD) risk is crucial for prevention and management, but the performance of the pooled cohort equations in older adults with frailty and multimorbidity is unknown. We evaluated the pooled cohort equations in these subgroups and the impact of competing risks. Methods and Results In 4249 community-dwelling adults, aged ≥65 years, from the CHS (Cardiovascular Health Study), we calculated 10-year risk of hard ASCVD. Frailty was determined using the Fried phenotype. Latent class analysis was used to identify individuals with multimorbidity patterns using chronic conditions. We assessed discrimination using the C-statistic and calibration by comparing predicted ASCVD risks with estimated risk using cause-specific and cumulative incidence models, by multimorbidity patterns and frailty status. A total of 917 (21.6%) participants had an ASCVD event, and 706 (16.6%) had a competing event of death. C-statistic was 0.68 in men and 0.69 in women; calibration was good when compared with cause-specific and cumulative incidence estimated risks (males, -0.1% and 3.3%; females, 0.6% and 1.4%). Latent class analysis identified 4 patterns minimal disease, cardiometabolic, low cognition, musculoskeletal-lung depression. In the cardiometabolic pattern, ASCVD risk was overpredicted compared with cumulative incidence risk in men (7.4%) and women (6.8%). Risk was underpredicted in men (-10.7%) and women (-8.2%) with frailty compared with cause-specific risk. Miscalibration occurred mostly at high predicted risk ranges. Conclusions ASCVD prediction was good in this cohort of adults aged ≥65 years. Although calibration varied by multimorbidity patterns, frailty, and competing risks, miscalibration was mostly present at high predicted risk ranges and thus less likely to alter decision making for primary prevention therapy.