BackgroundSocioeconomically disadvantaged groups tend to experience more harm from the same level of exposure to alcohol as advantaged groups. Alcohol has multiple biological effects on the cardiovascular system, both potentially harmful and protective. We investigated whether the diverging relationships between alcohol drinking patterns and cardiovascular disease (CVD) mortality differed by life course socioeconomic position (SEP).Methods and findingsFrom 3 cohorts (the Counties Studies, the Cohort of Norway, and the Age 40 Program, 1987–2003) containing data from population-based cardiovascular health surveys in Norway, we included participants with self-reported information on alcohol consumption frequency (n = 207,394) and binge drinking episodes (≥5 units per occasion, n = 32,616). We also used data from national registries obtained by linkage. Hazard ratio (HR) with 95% confidence intervals (CIs) for CVD mortality was estimated using Cox models, including alcohol, life course SEP, age, gender, smoking, physical activity, body mass index (BMI), systolic blood pressure, heart rate, triglycerides, diabetes, history of CVD, and family history of coronary heart disease (CHD). Analyses were performed in the overall sample and stratified by high, middle, and low strata of life course SEP. A total of 8,435 CVD deaths occurred during the mean 17 years of follow-up. Compared to infrequent consumption (

peated attempts to lose weight by temporary dieting may result in weight cycling, eventually further gain of body fat, and possible metabolic adaptation. We tested this with a controlled experiment in C57BL/6J mice subjected to four weight cycles (WC), continuous hypercaloric feeding (HF), or low-fat feeding (LF). To search for genes involved in an adaptive mechanism to former weight cycling and avoid acute effects of the last cycle, the last hypercaloric feeding period was prolonged by an additional 2 wk before euthanization. Total energy intake was identical in WC and HF. However, compared with HF, the WC mice gained significantly more total body mass and fat mass and showed increased levels of circulating leptin and lipids in liver. Both the HF and WC groups showed increased adipocyte size and insulin resistance. Despite these effects, we also observed an interesting maintenance of circulating adiponectin and free fatty acid levels after WC, whereas changes in these parameters were observed in HF mice. Global gene expression was analyzed by microarrays. Weight-cycled mice were characterized by a downregulation of several clock genes (Dbp, Tef, Per1, Per2, Per3, and Nr1d2) in adipose tissues, which was confirmed by quantitative PCR. In 3T3-L1 cells, we found reduced expression of Dbp and Tef early in adipogenic differentiation, which was mediated via cAMP-dependent signaling. Our data suggest that clock genes in adipose tissue may play a role in metabolic adaptation to weight cycling. caloric restriction; metabolism; clock genes; obesity; adipokines WEIGHT CYCLING RESULTING FROM INTERMITTENT OVEREATING and dieting represents a major challenge for many individuals (27,58,63) and may ultimately promote further expansion of adipose tissue (11,32,46,53,65). Evolutionary conserved molecular mechanisms allow fine-tuning of metabolic processes to environmental cues. Fat storage is a key evolutionary process conducive to survival in organisms ranging from the worm C. elegans to humans (41). The adipocyte, being the primary fat-storing cell, responds to changes in energy availability in part by releasing the peptide hormones leptin and adiponectin. These potent hormones exert local, central, and peripheral effects, coordinating the systemic response to fasting/refeeding cycles by modulating energy storage/expenditure, appetite, biological rhythms, and other functions. In adipose tissue, signals such as leptin may modulate the capacity for lipogenesis in response to weight fluctuations, predisposing to compensatory fat regain during subsequent energy surplus (28,29,59). Identification of novel genes associated with a history of weight cycling may provide novel molecular insight into the evolutionary adaptation to variable availability of energy.To our knowledge, there are no reports on the genome-wide transcriptional responses to weight cycling in adipose tissues. In rats, it has been shown previously that weight cycling increases feed efficiency (the weight gained relative to the amount of energy ingested) and resista...

Background/Objectives:Seasonal variation may reduce the validity of 25-hydroxyvitamin D (25OHD) as a biomarker of vitamin D status. Here we aimed to identify potential determinants of seasonal variation in 25OHD concentrations and to evaluate cosinor modelling as a method to adjust single 25OHD measurements for seasonal variation.Subjects/Methods:In Caucasian cardiovascular patients (1999–2004), we measured 25OHD by liquid chromatography tandem mass spectrometry in 4116 baseline and 528 follow-up samples. To baseline values, we fitted a cosinor model for monthly concentrations of 25OHD. Using the model, we estimated each patient's adjusted annual 25OHD value. Further, we studied how covariates affected the annual mean 25OHD concentration and seasonal variation of the study cohort. To evaluate the model, we predicted follow-up measurements with and without covariates and compared accuracy with carrying forward baseline values and linear regression adjusting for season, common approaches in research and clinical practice, respectively.Results:The annual mean (59.6 nmol/l) was associated with participants' age, gender, smoking status, body mass, physical activity level, diabetes diagnosis, vitamin D supplement use and study site (adjusted models, P<0.05). Seasonal 25OHD variation was 15.8 nmol/l, and older age (>62 years) was associated with less variation (adjusted model, P=0.025). Prediction of follow-up measurements was more accurate with the cosinor model compared with the other approaches (P<0.05). Adding covariates to cosinor models did not improve prediction (P>0.05).Conclusions:We find cosinor models suitable and flexible for analysing and adjusting for seasonal variation in 25OHD concentrations, which is influenced by age.

Plasma 25OHD concentrations were inversely associated with cardiovascular mortality and nonlinearly (U-shaped) associated with all-cause mortality.

The article aims to describe the association between midlife body mass index (BMI) and cardiovascular disease (CVD)- and all-cause mortality, and to use early adulthood BMI as an instrumental variable for midlife BMI, in order to obtain an estimate less distorted by midlife confounders and reverse causality. Data from Norwegian health surveys (1974–2003) (midlife BMI, smoking, blood pressure, total cholesterol, heart rate), Military Conscription Records, National Tuberculosis Screenings (early adulthood BMI), National Educational Registry and Cause of Death Registry were linked. Participants with data on BMI in early adulthood and midlife were included (n = 148.886). Hazard Ratio (HR) for CVD mortality was higher in men with midlife obesity relative to normal weight (HR = 1.46(95% CI 1.25, 1.70). For all-cause mortality, HR was higher in those with obesity or underweight in midlife relative to normal weight (Men:HR = 1.19(95% CI 1.09, 1.29), HR = 2.49(95% CI 1.81, 3.43) Women:HR = 1.33(95% CI 1.13, 1.56), HR = 1.61(95% CI 1.22, 2.13)). In instrumental variable analyses, increased BMI became more strongly associated with CVD and all-cause mortality, and the increased risk of all-cause mortality among the underweight attenuated.

Background: Individuals suffering from schizophrenia have a reduced life expectancy with cardiovascular disease (CVD) as a major contributor. Low educational attainment is associated with schizophrenia, as well as with all-cause and CVD mortality. However, it is unknown to what extent low educational attainment can explain the increased mortality in individuals with schizophrenia. Aim: Here, we quantify associations between educational attainment and allcause and CVD mortality in individuals with schizophrenia, and compare them with the corresponding associations in the general population.

Seasonings and condiments can be candidate vehicles for micronutrient fortification if consumed consistently and if dietary practices ensure bioavailability of the nutrient. In this review, we identify factors that may affect the bioavailability of iron, vitamin A, zinc, and folic acid when added to seasonings and condiments and evaluate their effects on micronutrient status. We take into consideration the chemical and physical properties of different forms of the micronutrients, the influence of the physical and chemical properties of foods and meals to which fortified seasonings and condiments are typically added, and interactions between micronutrients and the physiological and nutritional status of the target population. Bioavailable fortificants of iron have been developed for use in dry or fluid vehicles. For example, sodium iron ethylenediaminetetraacetic acid (NaFeEDTA) and ferrous sulfate with citric acid are options for iron fortification of fish and soy sauce. Furthermore, NaFeEDTA, microencapsulated ferrous fumarate, and micronized elemental iron are potential fortificants in curry powder and salt. Dry forms of retinyl acetate or palmitate are bioavailable fortificants of vitamin A in dry candidate vehicles, but there are no published studies of these fortificants in fluid vehicles. Studies of zinc and folic acid bioavailability in seasonings and condiments are also lacking.

ObjectivesWe aimed to provide an integrated picture of the relationship between different facets of adverse social behaviour (ASB) at the workplace and sick leave.MethodsData from a randomly drawn prospective cohort of the general working population. Eligible respondents were interviewed in 2009, 2013 or 2016, and were registered with an employee relationship of at least 50 working days in the national register the year following the survey interviews (n=21 674 observations/13 470 respondents). We investigated the prospective associations of self-reported exposure to ASB, including threats/acts of violence, bullying and sexual harassment, with physician-certified sick leave of 1–16 days (ie, low level of sick leave (LLSL)) and >16 days (ie, high level of sick leave (HLSL)) by means of mixed effects logistic regression.ResultsThe prevalence of sick leave was 18.4% (n=3986 observations) for LLSL and 16.1% (n=3492 observations) for HLSL. The different facets of ASB were independently associated with higher odds of sick leave, with stronger associations for HLSL than for LLSL. Adjusted for sex, age, education level, occupation, previous sickness absence level, OR (95% CI) for HLSL was 1.97 (1.61 to 2.35) for threats/acts of violence, 1.97 (1.53 to 2.54) for bullying and 1.41 (1.10 to 1.79) for sexual harassment. The population risks of LLSL and HLSL attributable to ASB were 5.27 (95% CI 1.85 to 8.81) and 8.27% (95% CI 4.01 to 12.48), respectively.ConclusionsThreats/acts of violence, bullying and sexual harassment were all independent predictors of sick leave, with threats/acts of violence appearing as the single most important factor.