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DNA methylation-based biomarkers of aging are highly correlated with actual age. Departures of methylation-estimated age from actual age can be used to define epigenetic measures of child development or age acceleration (AA) in adults. Very little is known about genetic or environmental determinants of these epigenetic measures of aging. We obtained DNA methylation profiles using Infinium HumanMethylation450 BeadChips across five time-points in 1018 mother-child pairs from the Avon Longitudinal Study of Parents and Children. Using the Horvath age estimation method, we calculated epigenetic age for these samples. AA was defined as the residuals from regressing epigenetic age on actual age. AA was tested for associations with cross-sectional clinical variables in children. We identified associations between AA and sex, birth weight, birth by caesarean section and several maternal characteristics in pregnancy, namely smoking, weight, BMI, selenium and cholesterol level. Offspring of non-drinkers had higher AA on average but this difference appeared to resolve during childhood. The associations between sex, birth weight and AA found in ARIES were replicated in an independent cohort (GOYA). In children, epigenetic AA measures are associated with several clinically relevant variables, and early life exposures appear to be associated with changes in AA during adolescence. Further research into epigenetic aging, including the use of causal inference methods, is required to better our understanding of aging.

Jewish suicides increased heavily under Nazi-rule. This research investigated risk factors for dying from suicide according to sociodemographic characteristics, local context, and time periods. Nazi-registration of Amsterdam residents of Jewish origin in 1941 linked to death and suicide lists. The added suicides after the Nazi-invasion (1940, n = 115) and the suicides when deportation trains ran (1942/1943, n = 182) were each matched to 25 controls using sex and age. Suicide was compared across migrant, occupational, marital, and religious status and neighborhood religiosity. Conditional logistic regression was applied, stratified by time period. In 1940, immigrant (cf. native born, odds ratio (OR) 1.89, 95%CI 1.21–2.96, p =.005) and married Jews (cf. previously married) showed higher suicide risk; members of Israelite Congregations (cf. nonmembers, OR 0.35, 95%CI 0.22–0.56, p <.001) showed reduced risk. Jews living in low synagogue rate neighborhoods showed higher risk compared to those living in neighborhoods without any synagogues (OR 2.48, 95%CI 1.65–3.72, p <.001) while those living in high synagogue rate neighborhoods showed no increased risk (OR 0.58, 95%CI 0.30–1.11, p =.10). In 1942/1943, the association between religious status (OR 1.07, 95%CI 0.67, 1.72, p =.77), synagogue rate (OR 1.27, 95%CI 0.91–1.77, p =.16), immigrant status (OR 1.30, 95%CI 0.92–1.84, p =.14) and suicide attenuated; Jews in managerial/professional occupations (cf. workers) or unmarried (cf. married) showed higher risk. In 1940, immigrants' higher suicide risk likely indicates greater fear of Nazis while religious affiliation's lower risk might indicate a protective effect of religious belief. In 1942/1943, risk differences markedly attenuated likely indicating increased fear of Nazis among all Jews. Religiously affiliated Jews showed reduced risk of dying from suicide after the Nazi-invasion Jewish immigrants showed higher risk of dying from suicide after the Nazi-invasion By 1942/1943, these risks attenuated indicating fear of the Nazis spread and nullified religion's protection [ABSTRACT FROM AUTHOR]

Background: Identifying strategies that reduce the risk of illness and injury is an objective of sports science and medicine teams. No studies have examined the relationship between oxidative stress (OS) and illness or injury in international athletes undergoing periods of intensified training and competition. Purpose: The authors aimed to identify relationships between illness, injury, and OS. Methods: A longitudinal, observational study of elite male rowers (n = 10) was conducted over 18 weeks, leading into World Championships. Following a recovery day and a 12-hour fast, hydroperoxides (free oxygen radicals test) and total antioxidant capacity (free oxygen radicals defense) were measured in venous blood, with the ratio calculated as the oxidative stress index (OSI). At all study time points, athletes were independently dichotomized as ill or not ill, injured or not injured. OS data were compared between groups using independent t tests. A Cox proportional hazard model was used to assess the association of OS with injury and illness while adjusting for age and body mass index. Results: Free oxygen radicals defense was lower (P <.02) and OSI was higher (P <.001) with illness than without illness. Free oxygen radicals test and OSI were higher with injury than without injury (P <.001). A 0.5 mmol·L−1 increase in free oxygen radicals defense was associated with a 30.6% illness risk reduction (95% confidence interval, 7%–48%, P =.014), whereas 0.5 unit increase in OSI was related to a 11.3% increased illness risk (95% confidence interval, 1%–23%, P =.036). Conclusions: OS is increased in injured and ill athletes. Monitoring OS may be advantageous in assessing recovery from and in reducing injury and illness risk given the association. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES Early right-sided heart failure (RHF) was seen in 22% of recipients of a left ventricular assist device (LVAD) in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). However, the optimal treatment of post-LVAD RHF is not well known. Levosimendan has proven to be effective in patients with cardiogenic shock and in those with end-stage heart failure. We sought to evaluate the efficacy of levosimendan on post-LVAD RHF and 30-day and 1-year mortality. METHODS The EUROMACS Registry was used to identify adults with mainstream continuous-flow LVAD implants who were treated with preoperative levosimendan compared to a propensity matched control cohort. RESULTS In total, 3661 patients received mainstream LVAD, of which 399 (11%) were treated with levosimendan pre-LVAD. Patients given levosimendan had a higher EUROMACS RHF score [4 (2– 5.5) vs 2 (2– 4); P  < 0.001], received more right ventricular assist devices (RVAD) [32 (8%) vs 178 (5.5%); P  = 0.038] and stayed longer in the intensive care unit post-LVAD implant [19 (8–35) vs 11(5–25); P  < 0.001]. Yet, there was no significant difference in the rate of RHF, 30-day, or 1-year mortality. Also, in the matched cohort (357 patients taking levosimendan compared to an average of 622 controls across 20 imputations), we found no evidence for a difference in postoperative severe RHF, RVAD implant rate, length of stay in the intensive care unit or 30-day and 1-year mortality. CONCLUSIONS In this analysis of the EUROMACS registry, we found no evidence for an association between levosimendan and early RHF or death, albeit patients taking levosimendan had much higher risk profiles. For a definitive conclusion, a multicentre, randomized study is warranted. [ABSTRACT FROM AUTHOR]