Television viewing and low leisure-time physical activity in adolescence independently predict the metabolic syndrome in mid-adulthood

Objective: We investigated whether television (TV) viewing and low leisure-time physical activity in adolescence predict the metabolic syndrome in mid-adulthood. Research design and methods: TV viewing habits and participation in leisure-time physical activity at age 16 years were assessed by self-administered questionnaires in a population-based cohort in Northern Sweden. The presence of the metabolic syndrome at age 43 years was ascertained in 888 participants (82% of the baseline sample) using the International Diabetes Federation criteria. Odds ratios (ORs) and CIs were calculated using logistic regression. Results: The overall prevalence of the metabolic syndrome at age 43 years was 26.9%. Adjusted OR for the metabolic syndrome at age 43 years was 2.14 (95% CI 1.24–3.71) for those who reported “watching several shows a day” versus “one show/week” or less and 2.31 (1.13–4.69) for leisure-time physical activity “several times/month” or less compared with “daily” leisure-time physical activity at age 16 years. TV viewing at age 16 years was associated with central obesity, low HDL cholesterol, and hypertension at age 43 years, whereas low leisure-time physical activity at age 16 years was associated with central obesity and triglycerides at age 43 years. Conclusions: Both TV viewing and low leisure-time physical activity in adolescence independently predicted the metabolic syndrome and several of the metabolic syndrome components in mid-adulthood. These findings suggest that reduced TV viewing in adolescence, in addition to regular physical activity, may contribute to cardiometabolic health later in life

How does social support shape the association between depressive symptoms and labour market participation:a four-way decomposition

Background Little is known about factors that may explain the association between depressive symptoms and poor labour market participation (LMP). The aim of this study is to examine the mediation and interaction effects of social support on the association between depressive symptoms and LMP. Methods Data were used from 985 participants (91% of the initial cohort) of the Northern Swedish Cohort, a longitudinal study of Swedish participants followed from adolescence throughout adulthood. Depressive symptoms were measured at age 16, social support at age 21 and LMP from age 30 to 43. Poor LMP was defined as being unemployed for a total of 6 months or more between the ages of 30 and 43. A four-way decomposition approach was applied to identify direct, mediation and interaction effects, together and separately. Results Both depressive symptoms during adolescence and social support at young adulthood were associated with poor LMP [odds ratio (OR) = 1.70, 95% confidence interval (CI) 1.17-2.47 and OR = 2.56, 95% CI 1.78-3.68 respectively]. The association between depressive symptoms and poor LMP was partially mediated by a lack of social support. No interaction effect of a lack of social support was found. Conclusion The results suggest that depressive symptoms influence not only later LMP but also the intermediary level of social support, and in turn influencing later LMP. Recommendations for public health are to detect and treat depressive symptoms at an early stage and to focus on the development of social skills, facilitating the increased availability of social support, thereby improving future LMP

Is body size at birth related to circadian salivary cortisol levels in adulthood? Results from a longitudinal cohort study

<p>Abstract</p> <p>Background</p> <p>The hypothesis of fetal origins of adult disease has during the last decades received interest as an explanation of chronic, e.g. cardiovascular, disease in adulthood stemming from fetal environmental conditions. Early programming and enduring dysregulations of the hypothalamic-pituitary-adrenal (HPA axis), with cortisol as its end product, has been proposed as a possible mechanism by which birth weight influence later health status. However, the fetal origin of the adult cortisol regulation has been insufficiently studied. The present study aims to examine if body size at birth is related to circadian cortisol levels at 43 years.</p> <p>Methods</p> <p>Participants were drawn from a prospective cohort study (n = 752, 74.5%). Salivary cortisol samples were collected at four times during one day at 43 years, and information on birth size was collected retrospectively from delivery records. Information on body mass during adolescence and adulthood and on health behavior, medication and medical conditions at 43 years was collected prospectively by questionnaire and examined as potential confounders. Participants born preterm or < 2500 g were excluded from the main analyses.</p> <p>Results</p> <p>Across the normal spectrum, size at birth (birth weight and ponderal index) was positively related to total (area under the curve, AUC) and bedtime cortisol levels in the total sample. Results were more consistent in men than in women. Descriptively, participants born preterm or < 2500 g also seemed to display elevated evening and total cortisol levels. No associations were found for birth length or for the cortisol awakening response (CAR).</p> <p>Conclusions</p> <p>These results are contradictory to previously reported negative associations between birth weight and adult cortisol levels, and thus tentatively question the assumption that only low birth weight predicts future physiological dysregulations.</p

Impaired IL-23-dependent induction of IFN-gamma underlies mycobacterial disease in patients with inherited TYK2 deficiency

Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-alpha/beta (underlying viral diseases in the patients) and to IL-12 and IL-23 (underlying mycobacterial diseases). Cells homozygous for the common P1104A TYK2 allele have selectively impaired responses to IL-23 (underlying isolated mycobacterial disease). We report three new forms of TYK2 deficiency in six patients from five families homozygous for rare TYK2 alleles (R864C, G996R, G634E, or G1010D) or compound heterozygous for P1104A and a rare allele (A928V). All these missense alleles encode detectable proteins. The R864C and G1010D alleles are hypomorphic and loss-of-function (LOF), respectively, across signaling pathways. By contrast, hypomorphic G996R, G634E, and A928V mutations selectively impair responses to IL-23, like P1104A. Impairment of the IL-23-dependent induction of IFN-gamma is the only mechanism of mycobacterial disease common to patients with complete TYK2 deficiency with or without TYK2 expression, partial TYK2 deficiency across signaling pathways, or rare or common partial TYK2 deficiency specific for IL-23 signaling.ANRS Nord-Sud ; CIBSS ; CODI ; Comité para el Desarrollo de la Investigación ; Fulbright Future Scholarshi

Genomic Instability, Defective Spermatogenesis, Immunodeficiency, and Cancer in a Mouse Model of the RIDDLE Syndrome

Eukaryotic cells have evolved to use complex pathways for DNA damage signaling and repair to maintain genomic integrity. RNF168 is a novel E3 ligase that functions downstream of ATM,γ-H2A.X, MDC1, and RNF8. It has been shown to ubiquitylate histone H2A and to facilitate the recruitment of other DNA damage response proteins, including 53BP1, to sites of DNA break. In addition, RNF168 mutations have been causally linked to the human RIDDLE syndrome. In this study, we report that Rnf168−/− mice are immunodeficient and exhibit increased radiosensitivity. Rnf168−/− males suffer from impaired spermatogenesis in an age-dependent manner. Interestingly, in contrast to H2a.x−/−, Mdc1−/−, and Rnf8−/− cells, transient recruitment of 53bp1 to DNA double-strand breaks was abolished in Rnf168−/− cells. Remarkably, similar to 53bp1 inactivation, but different from H2a.x deficiency, inactivation of Rnf168 impairs long-range V(D)J recombination in thymocytes and results in long insertions at the class-switch junctions of B-cells. Loss of Rnf168 increases genomic instability and synergizes with p53 inactivation in promoting tumorigenesis. Our data reveal the important physiological functions of Rnf168 and support its role in both γ-H2a.x-Mdc1-Rnf8-dependent and -independent signaling pathways of DNA double-strand breaks. These results highlight a central role for RNF168 in the hierarchical network of DNA break signaling that maintains genomic integrity and suppresses cancer development in mammals

Binge drinking and total alcohol consumption from 16 to 43 years of age are associated with elevated fasting plasma glucose in women : results from the northern Swedish cohort study

Background: Studies have indicated that moderate alcohol consumption is associated with lower incidence of diabetes in women. However, not only the amount but also the drinking pattern could be of importance when assessing the longitudinal relation between alcohol and glucose. Also, there is a lack of studies on alcohol use beginning in adolescence on adult glucose levels. The aim was to examine the association between total alcohol consumption and binge drinking between ages 16 and 43 and fasting plasma glucose at age 43. Methods: Data were retrieved from a 27-year prospective cohort study, the Northern Swedish Cohort. In 1981, all 9th grade students (n = 1083) within a municipality in Sweden were invited to participate. There were re-assessments at ages 18, 21, 30 and 43. This particular study sample consisted of 897 participants (82.8%). Fasting plasma glucose (mmol/L) was measured at a health examination at age 43. Total alcohol consumption (in grams) and binge drinking were calculated from alcohol consumption data obtained from questionnaires. Results: Descriptive analyses showed that men had higher levels of fasting plasma glucose as compared to women. Men also reported higher levels of alcohol consumption and binge drinking behavior. Linear regressions showed that total alcohol consumption in combination with binge drinking between ages 16 and 43 was associated with elevated fasting plasma glucose at age 43 in women (beta = 0.14, p = 0.003) but not in men after adjustment for BMI, hypertension and smoking at age 43. Conclusions: Our findings indicate that reducing binge drinking and alcohol consumption among young and middle-aged women with the highest consumption might be metabolically favorable for their future glucose metabolism

Mental health and parenthood - a longitudinal study of the relationship between self-reported mental health and parenthood

According to previous studies, the relationship between parenthood and mental health is not straightforward. One reason could be that selection effects on parenthood are seldom accounted for. Using the unique Northern Swedish Cohort dataset, following individuals from age 16 to 43 (n=1001), this study examines whether there is a selection effect of self-reported mental health in adolescence into parenthood; and whether entry into parenthood is related to subsequent mental health after controlling for prior mental health. Our results show no evidence of a selection effect for women, but men with poor mental health at age 16 were less likely to become fathers. Having children improved women's subsequent mental health after controlling for adolescent mental health, something that was not true for men. Our result reinforces the need for future research of the complex relationship between mental health and parenthood through focusing on, for example, timing of parenthood as well as through using different mental health measures

Lymph node CEA and MUC2 mRNA as useful predictors of outcome in colorectal cancer

The aim was to explore the utility for staging and prognostic impact of carcinoembryonic antigen (CEA), cytokeratin 20 (CK20), guanylyl cyclase C (GCC), CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor, and bone morphogenic protein 1) containing domain protein 1 (CDCP1) and mucin 2 (MUC2) mRNA levels in mesenteric lymph nodes of colorectal cancer (CRC) patients. Lymph nodes were collected at surgery and bisected; one half was subjected to biomarker mRNA analysis using real-time quantitative RT-PCR and the other half to routine histopathology. Lymph nodes from 174 CRC patients and 24 controls were analyzed. The median follow-up time was 59 (range 17-131) months. Cut-off levels were defined by analyzing quintiles by Cox regression model. CEA mRNA showed the best discriminating power between patients with recurrence in CRC after surgery and patients who were apparently disease-free (p = 0.015). The risk of recurrence for the CEA(+) patients was 4.6 times greater than for the CEA(-) patients (p < 0.0001). The other biomarkers gave lower hazard ratios. Cumulative survival analysis demonstrated that the average survival time was 99 months for CEA(-) patients compared to 39 months for CEA(+) patients, a difference of 60 months (p < 0.0001). Six to nine percent of the Stage I and Stage II patients [H&E(-)] had CEA(+), CK20(+), GCC(+) and/or MUC2(+) lymph nodes. Two of these patients died from recurrent CRC. Low lymph node MUC2/CEA mRNA ratio identified patients with high risk for recurrence (p = 0.011). Thus, quantitative reverse transcriptase-polymerase chain reaction of CEA mRNA is a sensitive method to identify tumor cells in lymph nodes of CRC patients and, in combination with MUC2 mRNA, allows improved prediction of clinical outcome