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Background: The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods: For this analysis, we constructed burden-weighted dose-response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15-95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. Findings: The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15-39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0-0) and 0·603 (0·400-1·00) standard drinks per day, and the NDE varied between 0·002 (0-0) and 1·75 (0·698-4·30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0·114 (0-0·403) to 1·87 (0·500-3·30) standard drinks per day and an NDE that ranged between 0·193 (0-0·900) and 6·94 (3·40-8·30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59·1% (54·3-65·4) were aged 15-39 years and 76·9% (73·0-81·3) were male. Interpretation: There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Research reported in this publication was supported by the Bill & Melinda Gates Foundation. S Afzal acknowledges the support for intellectual contributions to this manuscript by the Department of Community Medicine and Epidemiology at King Edward Medical University, Lahore, Pakistan. T Bärnighausen was supported by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research. L Belo acknowledges support from FCT in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of UCIBIO and the project LA/P/0140/2020 of i4HB. D Bennett is supported by the UK Medical Research Council Population Health Research Unit at the University of Oxford (Oxford, UK). M Carvalho acknowledges support from FCT in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of UCIBIO and the project LA/P/0140/2020 of i4HB. L Castro-de-Araujo was funded by the Medical Research Council (UK), Grant no. MR/T03355X/1 and by the National Institute of Mental Health Grant no. R01MH128911. FJ Elgar is supported by the Canada Research Chairs program. F Greaves acknowledges support from the NIHR Applied Research Collaboration for NW London. V K Gupta acknowledges funding support from the National Health and Medical Research Council (NHMRC), Australia. VB Gupta acknowledges funding support from the National Health and Medical Research Council (NHMRC), Australia. C Herteliu is partially supported by a grant from the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. C Herteliu is partially supported by a grant from the Romanian Ministry of Research Innovation and Digitalization, MCID, project number ID-585-CTR-42-PFE-2021. S Hussain was supported by the Operational Programme Research, Development and Education –Project, Postdoc2MUNI “(No. CZ.02.2.69/0.0/0.0/18_053/0016952). S M S Islam is funded by the National Health and Medical Research Council and received funding from the National Heart Foundation of Australia. The Serbian part of this GBD-related contribution has been co-financed through Grant OI 175 014 of the Ministry of Education Science and Technological Development of the Republic of Serbia. M Kivimaki was supported by the Wellcome Trust (221854/Z/20/Z), the UK Medical Research Council (MR/S011676/1), the US National Institute on Aging (R01AG056477), and the Academy of Finland (350426). K Krishan is supported by the UGC Centre of Advanced Study (Phase II), awarded to the Department of Anthropology, Panjab University, Chandigarh, India. B Lacey acknowledges support from the UK Biobank, funded largely by the UK Medical Research Council and Wellcome. S Lorkowski acknowledges institutional support from the Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig (Germany; German Federal Ministry of Education and Research; grant agreement number 01EA1808A). G Lucchetti received a productivity scholarship from the Brazilian National Council for Scientific and Technological Development — CNPq (Level 1D). J McGrath was supported by the Danish National Research Foundation (Niels Bohr Professor). J McGrath is employed by the Queensland Centre for Mental Health Research (Australia), which receives support from the Queensland Health Department. C Parry acknowleges the South African Medical Research Council. A Peden is supported by a National Health and Medical Research Council Emerging Leadership Fellowship (Grant ID: APP2009306). M R Phillips was supported in part by the Global Alliance for Chronic Diseases - National Natural Science Foundation of China (NSFC. No. 81761128031). M Pinheiro acknowledges FCT for funding through program DL 57/2016 – Norma transitória. A Rahman acknowledges the support from the Data Science Research Unit in Charles Sturt University (Bathurst, NSW, Australia). U Saeed would like to acknowledge the International Center of Medical Sciences Research (ICMSR), Islamabad, Pakistan. A M Samy acknowledges support from Ain Shams University (Cairo, Egypt) and the Egyptian Fulbright Mission Program. N Senthil Kumar acknowledges the DBT, New Delhi sponsored Advanced State Level Biotech Hub (BT/NER/143/SP44475/2021), Mizoram University (Aizawl, Mizoram, India) for facilitating this work. F Sha is supported by the Shenzhen Science and Technology Program (Grant No. KQTD20190929172835662). A Shetty acknowledges Kasturba Medical College (Mangalore, India) and Manipal Academy of Higher Education (Manipal, India) for all the academic support. R Shrestha acknowledges a career development award from the National Institutes of Health (K01DA051346). D Silva was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brazil (CAPES)-Finance Code 001 and is supported in part by CNPq - Brazil (309589/2021-5). D Sleet acknowledges partial support from Veritas Management Group, Inc and The Bizzell Group, LLC. S Trias-Llimós acknowledges research funding from the Juan de la Cierva-Formación program of the Spanish Ministry of Science and Innovation (FJC-2019-039314-I). Sí

Background People with intermediate hyperglycemia (IH), including impaired fasting glucose and/or impaired glucose tolerance, are at higher risk of developing type 2 diabetes (T2D) than those with normoglycemia. We aimed to evaluate the performance of published T2D risk prediction models in Chinese people with IH to inform them about the choice of primary diabetes prevention measures. Methods A systematic literature search was conducted to identify Asian-derived T2D risk prediction models, which were eligible if they were built on a prospective cohort of Asian adults without diabetes at baseline and utilized routinely-available variables to predict future risk of T2D. These Asian-derived and five prespecified non-Asian derived T2D risk prediction models were divided into BASIC (clinical variables only) and EXTENDED (plus laboratory variables) versions, with validation performed on them in three prospective Chinese IH cohorts: ACE (n = 3241), Luzhou (n = 1333), and TCLSIH (n = 1702). Model performance was assessed in terms of discrimination (C-statistic) and calibration (Hosmer–Lemeshow test). Results Forty-four Asian and five non-Asian studies comprising 21 BASIC and 46 EXTENDED T2D risk prediction models for validation were identified. The majority were at high (n = 43, 87.8%) or unclear (n = 3, 6.1%) risk of bias, while only three studies (6.1%) were scored at low risk of bias. BASIC models showed poor-to-moderate discrimination with C-statistics 0.52–0.60, 0.50–0.59, and 0.50–0.64 in the ACE, Luzhou, and TCLSIH cohorts respectively. EXTENDED models showed poor-to-acceptable discrimination with C-statistics 0.54–0.73, 0.52–0.67, and 0.59–0.78 respectively. Fifteen BASIC and 40 EXTENDED models showed poor calibration (P NAVIGATOR model showed the best discrimination in the three cohorts but had poor calibration (P Conclusions In Chinese people with IH, previously published BASIC models to predict T2D did not exhibit good discrimination or calibration. Several EXTENDED models performed better, but a robust Chinese T2D risk prediction tool in people with IH remains a major unmet need.

Context Circulating branched-chain amino acids (BCAAs) are associated with the risk of type 2 diabetes (T2D). Objective We examined to what extent lifestyle intervention aiming to prevent T2D interacts with this association and how BCAA concentrations change during the intervention. Methods We computed trajectory clusters by k-means clustering of serum fasting BCAAs analyzed annually by mass spectrometry during a 4-year intervention. We investigated whether baseline BCAAs, BCAA trajectories, and BCAA change trajectories predicted T2D and whether BCAAs predicted T2D differently in the intervention (n = 198) and control group (n = 196). Results Elevated baseline BCAAs predicted the incidence of T2D in the control group (hazard ratio [HR] 1.05 per 10 μmol/L, P = 0.01), but not in the intervention group. BCAA concentration decreased during the first year in the whole cohort (mean −14.9 μmol/L, P Conclusion Lifestyle intervention modified the association of the baseline BCAA concentration and BCAA trajectories with the incidence of T2D. Our study adds to the accumulating evidence on the mechanisms behind the effect of lifestyle changes on the risk of T2D.

Background Living in single parent and blended families or as an only child-compared to living in two-parent biological families or with siblings, respectively-is associated with a higher body mass index (BMI) in cross-sectional studies. However, longitudinal research addressing the children's BMI in this context is scarce. Further, little is known about the association between family structure and metabolic health. Objectives This study aimed at investigating the association between both aspects of family structure with BMI and a metabolic score (MetS). Methods Cross-sectional data from 7804 children participating in the European multi-center I.Family study (2013/2014) and longitudinal data from 5621 children who also participated previously in the IDEFICS study (2007-2010) were used. Family structure was assessed by a detailed interview. BMI z-score and the MetS were based on measured anthropometry, blood pressure, high-density lipoprotein, blood glucose, and triglycerides. Linear regressions were performed to model associations between family structure with BMI and MetS. Results Children from single-parent families had higher BMI z-scores in the cross-sectional (beta = 0.09, 95% confidence interval [CI]: 0.001 to 0.18) and longitudinal analyses compared to those from two-parent families. Cross-sectionally, the number of siblings was associated with lower BMI z-scores (beta = -0.07, 95% CI: -0.10 to -0.03) and lower MetS (beta = -0.14, 95% CI: -0.26 to -0.01). Longitudinally, only children between baseline and follow-up had higher BMI z-scores at follow-up (beta = 0.07, 95% CI: 0.01 to 0.14) compared to stable siblings. Conclusion Obesity prevention measures should focus on single-parent households and families with an only child.

Aim: To determine the extent to which change in (i.e., start and end of) workplace bullying can be predicted by employee responses to standard workplace surveys. Methods: Responses to an 87-item survey from 48,537 Finnish public sector employees at T1 (2017-2018) and T2 (2019-2020) were analyzed with least-absolute-shrinkage-and-selection-operator (LASSO) regression. The predictors were modelled both at the individual- and the work unit level. Outcomes included both the start and the end of bullying. Predictive performance was evaluated with C-indices and density plots.Results: The model with best predictive ability predicted the start of bullying with individual-level predictors, had a C-index of 0.68 and included 25 variables, of which 6 remained in a more parsimonious model: discrimination at work unit, unreasonably high workload, threat that some work tasks will be terminated, working in a work unit where everyone did not feel they are understood and accepted, having a supervisor who was not highly trusted, and a shorter time in current position. Other models performed even worse, either from the point of view of predictive performance, or practical useability.Discussion: While many bivariate associations between socioeconomic characteristics, work characteristics, leadership, team climate, and job satisfaction were observed, reliable individualized detection of individuals at risk of becoming bullied at workplace was not successful. The predictive performance of the developed risk scores was suboptimal, and we do not recommend their use as an individual-level risk prediction tool. However, they might be useful tool to inform decision-making when planning the contents of interventions to prevent bullying at an organizational level.

Background Disturbed sleep is associated with mood disorders. Both depression and insomnia may increase the risk of disability retirement. The longitudinal links among insomnia, depression and work incapacity are poorly known. Methods We examined association of self-reported sleep quality with incident symptoms of depression and disability retirement due to depressive disorders in a longitudinal population-based sample of twins ( n =12,063 individuals). These adults were categorized by their sleep quality in 1975 and 1981, excluding individuals with depressed mood in 1975/1981. The outcomes were the Beck Depression Inventory (BDI tot ) and its subscale Negative Attitudes Towards Self (BDI NATS ) in 1990 as dichotomized measures, and the incidence of disability retirement due to depressive disorder during 1991–2004. Results Onset of poor sleep between 1975 and 1981 predicted incident depression (BDI tot OR=4.5, 95% CI: 2.7–7.4, BDI NATS OR=2.0, 95% CI: 1.4–2.7), while persistent poor sleep showed somewhat weaker effects (BDI tot ; OR=2.5, 95% CI: 1.0–6.0, BDI NATS OR=1.9, 95% CI: 1.1–3.3). Among those with few recent stressful life events, onset of poor sleep predicted strongly depression (BDI NATS OR=9.5, 95% CI: 3.7–24.2). Likewise onset of poor sleep by 1981 increased the risk of disability retirement due to depression (OR=2.9, 95% CI: 1.8–4.9) with a similar risk among those with persistent poor sleep (OR=2.7, 95% CI: 1.3–5.7). Limitations Lack of baseline diagnostic interviews; sleep quality based on self-report. Conclusions Poor sleep is of importance in etiology of depression and disability retirement due to depression. This emphasizes the importance of early detection and treatment of sleep disturbances.

Introduction: The 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) multidomain lifestyle intervention trial (NCT01041989) demonstrated beneficial effects on cognition. We investigated whether sociodemographics, socioeconomic status, baseline cognition, or cardiovascular factors influenced intervention effects on cognition. Methods: The FINGER recruited 1260 people from the general Finnish population (60-77 years, at risk for dementia). Participants were randomized 1: 1 to multidomain intervention (diet, exercise, cognition, and vascular risk management) and regular health advice. Primary outcome was change in cognition (Neuropsychological Test Battery z-score). Prespecified analyses to investigate whether participants' characteristics modified response to intervention were carried out using mixed-model repeated-measures analyses. Results: Sociodemographics (sex, age, and education), socioeconomic status (income), cognition (Mini-Mental State Examination), cardiovascular factors (body mass index, blood pressure, cholesterol, fasting glucose, and overall cardiovascular risk), and cardiovascular comorbidity did not modify response to intervention (P-values for interaction > .05). Conclusions: The FINGER intervention was beneficial regardless of participants' characteristics and can thus be implemented in a large elderly population at increased risk for dementia. (C) 2017 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.

Objectives To gain a deeper understanding of fourth year medical students’ reflections on emotions in the context of breaking bad news (BBN). Methods During the years 2010–2012, students reflected on their emotions concerning BBN in a learning assignment at the end of the communications skills course. The students were asked to write a description of how they felt about a BBN case. The reflections were analysed using qualitative content analysis. Results 351 students agreed to participate in the study. We recognized ten categories in students’ reflections namely empathy, insecurity, anxiety, sadness, ambivalence, guilt, hope, frustration, gratefulness and emotional detachment. Most students expressed empathy, but there was a clear tension between feeling empathy and retaining professional distance by emotional detachment. Conclusions Students experience strong and perplexing emotions during their studies, especially in challenging situations. A deeper understanding of students' emotions is valuable for supporting students’ professional development and coping in their work in the future. Practice implications Medical students need opportunities to reflect on emotional experiences during their education to find strategies for coping with them. Emotions should be actively discussed in studies where the issues of BBN are addressed. Teachers need education in attending emotional issues constructively.

Our aim is to describe the study recruitment and baseline characteristics of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) study population. Potential study participants (age 60–77 years, the dementia risk score ≥6) were identified from previous population-based survey cohorts and invited to the screening visit. To be eligible, cognitive performance measured at the screening visit had to be at the mean level or slightly lower than expected for age. Of those invited (n = 5496), 48% (n = 2654) attended the screening visit, and finally 1260 eligible participants were randomized to the intervention and control groups (1:1). The screening visit non-attendees were slightly older, less educated, and had more vascular risk factors and diseases present. The mean (SD) age of the randomized participants was 69.4 (4.7) years, Mini-Mental State Examination 26.7 (2.0) points, systolic blood pressure 140.1 (16.2) mmHg, total serum cholesterol 5.2 (1.0) mmol/L for, and fasting glucose 6.1 (0.9) mmol/L for, with no difference between intervention and control groups. Several modifiable risk factors were present at baseline indicating an opportunity for the intervention. The FINGER study will provide important information on the effect of lifestyle intervention to prevent cognitive impairment among at risk persons.

Island populations are on average smaller, genetically less diverse, and at a higher risk to go extinct than mainland populations. Low genetic diversity may elevate extinction probability, but the genetic component of the risk can be affected by the mode of diversity loss, which, in turn, is connected to the demographic history of the population. Here, we examined the history of genetic erosion in three Fennoscandian ringed seal subspecies, of which one inhabits the Baltic Sea ‘mainland’ and two the ‘aquatic islands’ composed of Lake Saimaa in Finland and Lake Ladoga in Russia. Both lakes were colonized by marine seals after their formation c. 9500 years ago, but Lake Ladoga is larger and more contiguous than Lake Saimaa. All three populations suffered dramatic declines during the 20th century, but the bottleneck was particularly severe in Lake Saimaa. Data from 17 microsatellite loci and mitochondrial control-region sequences show that Saimaa ringed seals have lost most of the genetic diversity present in their Baltic ancestors, while the Ladoga population has experienced only minor reductions. Using Approximate Bayesian computing analyses, we show that the genetic uniformity of the Saimaa subspecies derives from an extended founder event and subsequent slow erosion, rather than from the recent bottleneck. This suggests that the population has persisted for nearly 10,000 years despite having low genetic variation. The relatively high diversity of the Ladoga population appears to result from a high number of initial colonizers and a high post-colonization population size, but possibly also by a shorter isolation period and/or occasional gene flow from the Baltic Sea.

Backgrounds. Research findings suggest that the mind can cause physical disease. To plan the best quality of care, general practitioner needs to understand an individual's health problems in physical, social, and psychological dimensions. This study sought to establish whether adverse life events occurring in childhood and adolescence are associated with diabetes. Methods. The cohort was collected from the health and social support (HeSSup) study—a postal follow-up survey of randomized working-aged Finns initiated in 1998. The response rate was 40.0% and the final cohort size 24057. Data on reimbursed diabetes medication during the years 1998–2006 were obtained from the Social Insurance Institute of Finland registers. Subjects were divided into insulin, tablet, combination therapy, and drug-naive groups together with a control group without diabetes. The prevalence of childhood adversities was assessed based on answers to six survey questions. Results. Childhood adversities showed predominant linkage to diabetes type 2 groups, especially to the combination therapy group requiring combined insulin and tablet treatment. No connection was found between childhood adversities and insulin use. Cumulative adversities did not markedly increase the association. Conclusions. Stressful events in childhood are associated with diabetes combination therapy in working age. The meaning of the relationship remains unsolved.

To analyze the effects of genetic and environmental factors on sense of coherence (SOC) in young adulthood and whether family environment measured in childhood modifies these effects.SOC was measured at 20-27 years of age in 3,193 Finnish twins using the Antonovsky's 13-item short scale. The twins and their parents had rated their emotional family environment independently when the twins were 12 years of age. The data were analyzed using applications of structural linear equation modeling to twin data.Females rated SOC 2.42 points lower than males. Additive genetic factors explained 39% of the variation of SOC in males and 49% in females, whereas the rest of the variation was explained by environmental factors unique to each twin individual. For the dimensions of SOC, the highest genetic correlation was found between comprehensibility and manageability (0.90 in males and 0.97 in females). SOC was strongest in the participants who had reported supportive family atmosphere and low relational tensions to parents in childhood. These participants also had higher genetic variance and lower unique environmental variance of SOC when compared to those who reported emotionally more stressful family environment. The results were similar when we used parental rating of family environment.Genetic factors are important for SOC, but genetic influences are much greater in supportive family environments. This emphasizes the importance of childhood home for the development of strong SOC.

OBJECTIVE Melatonin synthesis and secretion are partly modulated by estrogen and progesterone. Changes in melatonin concentrations, possibly related to the menopausal transition, may be associated with climacteric mood, sleep, and vasomotor symptoms. The aims of this study were to compare the serum concentrations of melatonin in perimenopausal and postmenopausal women and to evaluate melatonin's influence on mood, sleep, vasomotor symptoms, and quality of life. METHODS We analyzed the data of 17 healthy perimenopausal women (aged 43-51 y) and 18 healthy postmenopausal women (aged 58-71 y) who participated in a prospective study. On study night (9:00 pm-9:00 am), serum melatonin was sampled at 20-minute (9:00 pm-12:00 midnight; 6:00-9:00 am) and 1-hour (12:00 midnight-6:00 am) intervals. Questionnaires were used to assess depression (Beck Depression Inventory), anxiety (State-Trait Anxiety Inventory), insomnia and sleepiness (Basic Nordic Sleep Questionnaire [BNSQ]), subjective sleep quality, vasomotor symptoms, and quality of life (EuroQoL). RESULTS Postmenopausal women had lower nighttime serum melatonin concentrations than perimenopausal women. The duration of melatonin secretion tended to be shorter in postmenopause, whereas melatonin peak time did not differ. Mean melatonin concentrations and exposure levels did not correlate with follicle-stimulating hormone level, estradiol level, body mass index, Beck Depression Inventory score, State-Trait Anxiety Inventory score, BNSQ insomnia score, BNSQ sleepiness score, subjective sleep score, climacteric vasomotor score, or quality of life. In perimenopause, the later is the melatonin peak, the higher is the level of anxiety (P = 0.022), and the longer is the melatonin secretion, the better is the quality of life (P < 0.001). CONCLUSIONS Longitudinal research is needed to better understand the possible contributory role of menopause in lower melatonin levels.

The aim of this study was to determine the prevalence of impaired glucose regulation in male Finnish former elite athletes and age- and area-matched controls. We hypothesised that vigorous physical activity during young adulthood protects from disturbances in glucose regulation in later life.In 2008, 392 former male elite athletes (mean age 72.7 ± 6.1 years) and 207 controls (mean age 71.6 ± 5.6 years) participated in a clinical study (participation rate: 50.6%). The former athletes were divided into three groups based on their active career sport: endurance, mixed and power sports. Participants without a history of diabetes (n = 537) underwent a 2 h 75 g OGTT. Current volume of leisure-time physical activity (LTPA) was determined by self-reported questionnaires and expressed in metabolic equivalent hours (MET-h). Data on reimbursable diabetes medication from participants and non-participants was obtained from the register of the Finnish Social Insurance Institution.Compared with the controls, the former elite athletes had a significantly lower risk of type 2 diabetes (OR 0.72, 95% CI 0.53, 0.98). The risk of type 2 diabetes decreased with increased LTPA volume (OR 0.98, 95% CI 0.97, 0.99 per 1 MET-h/week). The former elite athletes also had a significantly lower risk of impaired glucose tolerance (IGT) than the controls (OR 0.58, 95% CI 0.38, 0.87).A former career as an elite athlete protected from both type 2 diabetes and IGT in later life. In addition, the volume of current LTPA was inversely associated with the prevalence of type 2 diabetes.

The purpose of the present study was to examine the combined effects of aging and lifelong ethanol exposure on the levels of monoamine neurotransmitters in different regions of the brain. This work is part of a project addressing interactions of aging and lifelong ethanol consumption in alcohol-preferring AA (Alko Alcohol) line of rats, selected for high voluntary consumption of ethanol. Intake of ethanol on the level of 4.5–5 g/kg/day for about 20 months induced only limited changes in the neurotransmitter levels; the concentration of noradrenaline was significantly reduced in the frontal cortex. There was also a trend towards lower levels of dopamine and 5-hydroxytryptamine (5-HT) in the frontal cortex, and towards a lower noradrenaline level in the dorsal cortex. Aging was associated with a decreased concentration of dopamine in the dorsal cortex and with a declining trend in the striatum. The levels of 5-HT in the limbic forebrain were higher in the aged than in the young animals, and in the striatum, there was a trend towards higher levels in older animals. The data suggest that a continuous intake of moderate amounts of ethanol does not enhance the age-related alterations in brain monoamine neurotransmission, while the decline in the brain level of dopamine associated with aging may be a factor contributing to age-related neurological disorders.

Objective. To evaluate oral health literacy, independent of other oral health determinants, as a risk indicator for self-reported oral health. Methods. A cross-sectional population-based survey conducted in Tehran, Iran. Multiple logistic regression analysis served to estimate the predictive effect of oral health literacy on self-reported oral health status (good versus poor) controlling for socioeconomic and demographic factors and tooth-brushing behavior. Results. In all, among 1031 participants (mean age 36.3 (SD 12.9); 51% female), women reported brushing their teeth more frequently (P<0.001) and scored higher for oral health literacy (mean 10.9 versus 10.2, P<0.001). In the adjusted model, high age (OR = 1.01, 95% CI 1.003–1.034), low education (OR = 1.88, 95% CI 1.23–2.87), small living area in square meters per person (OR = 1.85, 95% CI 1.003–3.423), poor tooth brushing behavior (OR = 3.35, 95% CI 2.02–5.57), and low oral health literacy scores (OR = 1.58, 95% CI 1.02–2.45) were significant risk indicators for poor self-reported oral health. Conclusions. Low oral health literacy level, independent of education and other socioeconomic determinants, was a predictor for poor self-reported oral health and should be considered a vital determinant of oral health in countries with developing health care systems.

WOS:000310015700004 Background and purpose The risk of revision due to infection after primary total hip arthroplasty (THA) has been reported to be increasing in Norway. We investigated whether this increase is a common feature in the Nordic countries (Denmark, Finland, Norway, and Sweden). Materials and methods The study was based on the Nordic Arthroplasty Register Association (NARA) dataset. 432,168 primary THAs from 1995 to 2009 were included (Denmark: 83,853, Finland 78,106, Norway 88,455, and Sweden 181,754). Adjusted survival analyses were performed using Cox regression models with revision due to infection as the endpoint. The effect of risk factors such as the year of surgery, age, sex, diagnosis, type of prosthesis, and fixation were assessed. Results 2,778 (0.6%) of the primary THAs were revised due to infection. Compared to the period 1995-1999, the relative risk (with 95% CI) of revision due to infection was 1.1 (1.0-1.2) in 2000-2004 and 1.6 (1.4-1.7) in 2005-2009. Adjusted cumulative 5-year revision rates due to infection were 0.46% (0.42-0.50) in 1995-1999, 0.54% (0.50-0.58) in 2000-2004, and 0.71% (0.66-0.76) in 2005-2009. The entire increase in risk of revision due to infection was within 1 year of primary surgery, and most notably in the first 3 months. The risk of revision due to infection increased in all 4 countries. Risk factors for revision due to infection were male sex, hybrid fixation, cement without antibiotics, and THA performed due to inflammatory disease, hip fracture, or femoral head necrosis. None of these risk factors increased in incidence during the study period. Interpretation We found increased relative risk of revision and increased cumulative 5-year revision rates due to infection after primary THA during the period 1995-2009. No change in risk factors in the NARA dataset could explain this increase. We believe that there has been an actual increase in the incidence of prosthetic joint infections after THA.

Objective. Our aim was to explore perceptions of periodontal health and illness and to examine attitudes and beliefs regarding prevention of gum diseases among Iranian adults. Methods. Our qualitative approach included focus-group discussions among adults aged 18 and above based on convenient and purposive sampling in Tehran. Transcripts of the four focus-group discussions were analyzed by two independent reviewers using a content analysis method. Results. Two major themes in the analyses emerged: the common perception of periodontal health and illness and the attitude towards prevention. The study demonstrated the subjects’ good understanding of prevention of periodontal disease, but their lack of knowledge of the aetiology of the diseases, and an inability to differentiate aetiology, symptoms, and prevention of dental caries and periodontal disease. Conclusion. This study revealed a need for oral health education among Iranian adults to improve their knowledge and change their attitudes to achieve deeper understanding of the aetiology and prevention of periodontal disease. Health promotion programs should address misconceptions about prevention of gum disease.

ObjectiveA low socio-economic status (SES) is related to less healthy dietary habits, but the reasons for this remain unclear. We examined whether the absolute or relative importance of various food choice motives contributed to SES disparities in vegetable/fruit and energy-dense food intake.DesignWe analysed cross-sectional data from the FINRISK Study 2007 by means of structural equation modelling and used a shortened version of the Food Choice Questionnaire to assess the absolute importance of health, pleasure, convenience, price, familiarity and ethicality motives. We calculated the relative importance of each motive by dividing the participant's rating of it by his/her mean score on all motives. Dietary intake was measured with an FFQ.SettingA population-based survey in Finland.SubjectsMen (n 1691) and women (n 2059) aged 25–64 years.ResultsHigher education and income were related to a greater vegetable/fruit intake (β = 0·12, P < 0·001), while education was associated negatively with the consumption of energy-dense foods (β = −0·09, P < 0·001). Socio-economically disadvantaged individuals considered price and/or familiarity more important in their food choices in both absolute and relative terms. A higher income was related to a greater relative importance of health considerations. Relative motives were more strongly associated with vegetable/fruit and energy-dense food consumption than absolute motives and the relative importance of price, familiarity and health partly mediated the effects of the SES indicators on the consumption of these food items.ConclusionsIndividual priorities in food choice motives, rather than the absolute importance of single motives, play a role in producing SES disparities in diet.

Retirement from paid work is a major life event facing increasingly large numbers of people in the coming years. We examined trajectories of mental health five years before and five years after old-age and disability retirement using data on purchases of psychotropic drugs.The study included all employees from the City of Helsinki, Finland, retiring between 2000-2008 due to old age (N=4456) or disability (N=2549). Purchases of psychotropic drugs were analyzed in 20 3-month intervals before and after retirement using graphical methods and growth curve models.Old-age retirement was unrelated to purchases of psychotropic drugs. Among disability retirees, psychotropic medication tripled before retirement. The average increase was 0.95 [95% confidence interval (95% CI) 0.73-1.16] daily defined doses (DDD) 5-1.5 years before retirement; from 1.5 years until retirement it was 5.68 DDD (95% CI 5.33-6.03) for each 3-month interval. After disability retirement, purchases of antidepressants decreased on average by 0.40 DDD (95% CI 0.57-0.23) for each 3-month interval, those of hypnotics and sedatives increased by 0.30 DDD (95% CI 0.12-0.47), and no changes were seen for other psychotropic drugs. The changes before and after retirement were largest among those who retired due to mental disorders and those whose retirement had been granted as temporary.While no overall decrease in psychotropic medication after retirement was observed, purchases of antidepressants decreased after disability retirement. Long-term trajectories suggest that disability retirement might be prevented if mental health problems were tackled more efficiently earlier in the pre-retirement period.

Aims Smoking initiation during childhood or adolescence is strongly associated with friends’ smoking. Likewise, adverse living conditions increase the likelihood of future deviant behaviour. We examine whether smoking by a best friend and family members during school years as well as adverse childhood experiences are associated with smoking in adulthood. Data and Design We have analysed the responses of Finnish working-aged respondents in 1998 (N=25901) and 2003 (N=20773) to questions on the smoking status of friends and family members during school years as well as their answers on a six-item scale of childhood adversities. A case-control study design was used to compare current cigarette smokers (1998 and 2003) to non-smokers (1998 and 2003). Results If a best friend during school years was a smoker, the subject s odds ratio (OR) of being a smoker in adulthood was 4.43 among females and 3.91 among males compared to those with a non-smoking best friend in multivariate models adjusted for smoking by family members during school years and by six childhood adversities. These associations did not differ by age. Smoking in adulthood was associated with childhood adversities, most strongly with parental divorce or separation during the subjects’ school years. Conclusion Smoking by a best friend and parental divorce or separation during school years appears to be a strong factor of smoking in later life.

Animal studies have suggested that angiopoietin-like 4 (Angptl4) regulates adiposity through central and peripheral mechanisms. The aim of this study was to investigate whether serum concentration and adipose tissue expression of Angptl4 are associated with obesity-related parameters in humans. Altogether, 75 dizygotic (DZ) and 46 monozygotic (MZ) twin pairs were studied, from the FinnTwin12 and FinnTwin16 cohorts. Among the MZ pairs, 21 were discordant for body mass index (BMI) (intra-pair BMI-difference >2.5 kg/m², age 23-33 years). Serum Angptl4 (s-Angptl4) levels were measured by ELISA, and adipose tissue gene expression was analyzed by genome-wide transcript profiling. In MZ twin pairs discordant for BMI, s-Angptl4 and adipose tissue ANGPTL4 mRNA (at-ANGPTL4) levels were significantly decreased (P = 0.04 and P = 0.03, respectively) in obese twins as compared with their nonobese cotwins. In all twins, intra-pair differences in s-Angptl4 levels were inversely correlated with intra-pair differences in BMI (r = -0.27, P = 0.003). In individual MZ twins, at-ANGPTL4 expression was inversely correlated with BMI (r = -0.44, P = 0.001) and positively correlated with at-LIPE (r = 0.24, P = 0.01) and at-ABHD5 (r = 0.41, P = 0.005) expression. Our results demonstrated that variation in Angptl4 concentration was only modestly accounted for by genetic factors and suggest a role for Angptl4 in acquired obesity in humans.

Background Ancient DNA analysis offers a way to detect changes in populations over time. To date, most studies of ancient cattle have focused on their domestication in prehistory, while only a limited number of studies have analysed later periods. Conversely, the genetic structure of modern cattle populations is well known given the undertaking of several molecular and population genetic studies. Results Bones and teeth from ancient cattle populations from the North-East Baltic Sea region dated to the Prehistoric (Late Bronze and Iron Age, 5 samples), Medieval (14), and Post-Medieval (26) periods were investigated by sequencing 667 base pairs (bp) from the mitochondrial DNA (mtDNA) and 155 bp of intron 19 in the Y-chromosomal UTY gene. Comparison of maternal (mtDNA haplotypes) genetic diversity in ancient cattle (45 samples) with modern cattle populations in Europe and Asia (2094 samples) revealed 30 ancient mtDNA haplotypes, 24 of which were shared with modern breeds, while 6 were unique to the ancient samples. Of seven Y-chromosomal sequences determined from ancient samples, six were Y2 and one Y1 haplotype. Combined data including Swedish samples from the same periods (64 samples) was compared with the occurrence of Y-chromosomal haplotypes in modern cattle (1614 samples). Conclusions The diversity of haplogroups was highest in the Prehistoric samples, where many haplotypes were unique. The Medieval and Post-Medieval samples also show a high diversity with new haplotypes. Some of these haplotypes have become frequent in modern breeds in the Nordic Countries and North-Western Russia while other haplotypes have remained in only a few local breeds or seem to have been lost. A temporal shift in Y-chromosomal haplotypes from Y2 to Y1 was detected that corresponds with the appearance of new mtDNA haplotypes in the Medieval and Post-Medieval period. This suggests a replacement of the Prehistoric mtDNA and Y- chromosomal haplotypes by new types of cattle.

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Aim The aim of this study was to investigate inflammatory and respiratory responses to welding fume exposure in patients with suspected occupational asthma. Methods Sixteen patients referred to the Finnish Institute of Occupational Health underwent mild steel (MS) and stainless steel (SS) welding challenge tests, due to suspicion of OA. Platelet count, leucocytes and their differential count, hemoglobin, sensitive CRP, lipids, glucose and fibrinogen were analyzed in addition to interleukin (IL)-1β, IL-6, IL-8, TNF-α, endothelin-1, and E-selectin in plasma samples. Peak expiratory flow (PEF), forced expiratory volume in 1 min (FEV 1 ) and exhaled nitric oxide (NO) measurements were performed before and after the challenge test. Personal particle exposure was assessed using IOM and a mini sampler. Particle size distribution was measured by an Electric Low Pressure Impactor (ELPI). Results The number of leukocytes, neutrophils, and platelets increased significantly, and the hemoglobin level and number of erythrocytes decreased significantly after both the MS and SS exposure tests. Five of the patients were diagnosed with OA, and their maximum fall in FEV 1 values was 0.70 l (±0.32) 4 h after SS exposure. MS welding generated an average inhalable particle mass concentration of 31.6, and SS welding of 40.2 mg/m 3 . The mean particle concentration measured inside the welding face shields by the mini sampler was 30.2 mg/m 3 and 41.7 mg/m 3 , respectively. Conclusions Exposure to MS and SS welding fume resulted in a mild systemic inflammatory response. The particle concentration from the breathing zones correlated with the measurements inside the welding face shields.

Background Migraine is a common comorbidity among individuals with bipolar disorder, but the underlying mechanisms for this co-occurrence are poorly understood. The aim of this study was to investigate the genetic background of bipolar patients with and without migraine. Methods We performed a genome-wide association analysis contrasting 460 bipolar migraneurs with 914 bipolar patients without migraine from the Bipolar Genome Study (BiGS). Results We identified one genome-wide significant association between migraine in bipolar disorder patients and rs1160720, an intronic single nucleotide polymorphism (SNP) in the NBEA gene ( P =2.97×10 −8 , OR: 1.82, 95% CI: 1.47–2.25), although this was not replicated in a smaller sample of 289 migraine cases. Limitations Our study is based on self-reported migraine. Conclusions NBEA encodes neurobeachin, a scaffolding protein primarily expressed in the brain and involved in trafficking of vesicles containing neurotransmitter receptors. This locus has not previously been implicated in migraine per se. We found no evidence of association in data from the GWAS migraine meta-analysis consortium ( n =118,710 participants) suggesting that the association might be specific to migraine co-morbid with bipolar disorder.

In the middle of the 1980?s, I heard a highly profiled professor making a comment after a lecture about a brand new technique, the polymerase chain reaction (PCR). His comment was full of doubt about this novel technology, and the message was something like: ? it [PCR] can never become a widely used diagnostic tool due to the unavoidable contamination? . However, the PCR revolutionized life sciences from medicine to conservation genetics, the inventor was awarded with the Noble Prize, and many of us made careers using the very technique. Scientists, clinical diagnostics and forensic laboratories and others using PCR quickly learned to deal with contamination and build mechanisms to monitor for it. The contamination was there, but, it could be managed with the right laboratory environment, sample flow, and careful experimental design including proper sample handling and a set of controls.

In this study, Wurtz and colleagues investigated to what extent elevated body mass index (BMI) within the normal weight range has causal influences on the detailed systemic metabolite profile in early adulthood using Mendelian randomization analysis. Please see later in the article for the Editors' Summary, Background Increased adiposity is linked with higher risk for cardiometabolic diseases. We aimed to determine to what extent elevated body mass index (BMI) within the normal weight range has causal effects on the detailed systemic metabolite profile in early adulthood. Methods and Findings We used Mendelian randomization to estimate causal effects of BMI on 82 metabolic measures in 12,664 adolescents and young adults from four population-based cohorts in Finland (mean age 26 y, range 16–39 y; 51% women; mean ± standard deviation BMI 24±4 kg/m2). Circulating metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. In cross-sectional analyses, elevated BMI was adversely associated with cardiometabolic risk markers throughout the systemic metabolite profile, including lipoprotein subclasses, fatty acid composition, amino acids, inflammatory markers, and various hormones (p, Editors' Summary Background Adiposity—having excessive body fat—is a growing global threat to public health. Body mass index (BMI, calculated by dividing a person's weight in kilograms by their height in meters squared) is a coarse indicator of excess body weight, but the measure is useful in large population studies. Compared to people with a lean body weight (a BMI of 18.5–24.9 kg/m2), individuals with higher BMI have an elevated risk of developing life-shortening cardiometabolic diseases—cardiovascular diseases that affect the heart and/or the blood vessels (for example, heart failure and stroke) and metabolic diseases that affect the cellular chemical reactions that sustain life (for example, diabetes). People become unhealthily fat by consuming food and drink that contains more energy (calories) than they need for their daily activities. So adiposity can be prevented and reversed by eating less and exercising more. Why Was This Study Done? Epidemiological studies, which record the patterns of risk factors and disease in populations, suggest that the illness and death associated with excess body weight is partly attributable to abnormalities in how individuals with high adiposity metabolize carbohydrates and fats, leading to higher blood sugar and cholesterol levels. Further, adiposity is also associated with many other deviations in the metabolic profile than these commonly measured risk factors. However, epidemiological studies cannot prove that adiposity causes specific changes in a person's systemic (overall) metabolic profile because individuals with high BMI may share other characteristics (confounding factors) that are the actual causes of both adiposity and metabolic abnormalities. Moreover, having a change in some aspect of metabolism could also lead to adiposity, rather than vice versa (reverse causation). Importantly, if there is a causal effect of adiposity on cardiometabolic risk factor levels, it might be possible to prevent the progression towards cardiometabolic diseases by weight loss. Here, the researchers use “Mendelian randomization” to examine whether increased BMI within the normal and overweight range is causally influencing the metabolic risk factors from many biological pathways during early adulthood. Because gene variants are inherited randomly, they are not prone to confounding and are free from reverse causation. Several gene variants are known to lead to modestly increased BMI. Thus, an investigation of the associations between these gene variants and risk factors across the systemic metabolite profile in a population of healthy individuals can indicate whether higher BMI is causally related to known and novel metabolic risk factors and higher cardiometabolic disease risk. What Did the Researchers Do and Find? The researchers measured the BMI of 12,664 adolescents and young adults (average BMI 24.7 kg/m2) living in Finland and the blood levels of 82 metabolites in these young individuals at a single time point. Statistical analysis of these data indicated that elevated BMI was adversely associated with numerous cardiometabolic risk factors. For example, elevated BMI was associated with raised levels of low-density lipoprotein, “bad” cholesterol that increases cardiovascular disease risk. Next, the researchers used a gene score for predisposition to increased BMI, composed of 32 gene variants correlated with increased BMI, as an “instrumental variable” to assess whether adiposity causes metabolite abnormalities. The effects on the systemic metabolite profile of a 1-kg/m2 increment in BMI due to genetic predisposition closely matched the effects of an observed 1-kg/m2 increment in adulthood BMI on the metabolic profile. That is, higher levels of adiposity had causal effects on the levels of numerous blood-based metabolic risk factors, including higher levels of low-density lipoprotein cholesterol and triglyceride-carrying lipoproteins, protein markers of chronic inflammation and adverse liver function, impaired insulin sensitivity, and elevated concentrations of several amino acids that have recently been linked with the risk for developing diabetes. Elevated BMI also causally led to lower levels of certain high-density lipoprotein lipids in the blood, a marker for the risk of future cardiovascular disease. Finally, an examination of the metabolic changes associated with changes in BMI in 1,488 young adults after a period of six years showed that those metabolic measures that were most strongly associated with BMI at a single time point likewise displayed the highest responsiveness to weight change over time. What Do These Findings Mean? These findings suggest that increased adiposity has causal adverse effects on multiple cardiometabolic risk markers in non-obese young adults beyond the effects on cholesterol and blood sugar. Like all Mendelian randomization studies, the reliability of the causal association reported here depends on several assumptions made by the researchers. Nevertheless, these findings suggest that increased adiposity has causal adverse effects on multiple cardiometabolic risk markers in non-obese young adults. Importantly, the results of both the causal effect analyses and the longitudinal study suggest that there is no threshold below which a BMI increase does not adversely affect the metabolic profile, and that a systemic metabolic profile linked with high cardiometabolic disease risk that becomes established during early adulthood can be reversed. Overall, these findings therefore highlight the importance of weight reduction as a key target for metabolic risk factor control among young adults. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001765. The Computational Medicine Research Team of the University of Oulu has a webpage that provides further information on metabolite profiling by high-throughput NMR metabolomics The World Health Organization provides information on obesity (in several languages) The Global Burden of Disease Study website provides the latest details about global obesity trends The UK National Health Service Choices website provides information about obesity, cardiovascular disease, and type 2 diabetes (including some personal stories) The American Heart Association provides information on all aspects of cardiovascular disease and diabetes and on keeping healthy; its website includes personal stories about heart attacks, stroke, and diabetes The US Centers for Disease Control and Prevention has information on all aspects of overweight and obesity and information about heart disease, stroke, and diabetes MedlinePlus provides links to other sources of information on heart disease, vascular disease, and obesity (in English and Spanish) Wikipedia has a page on Mendelian randomization (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)

Physical activity increases oxidative stress and therefore the antioxidant effects of vitamin C administration might become evident in people undertaking vigorous exercise. Vitamin C is involved in the metabolism of histamine, prostaglandins, and cysteinyl leukotrienes, all of which appear to be mediators in the pathogenesis of exercise-induced bronchoconstriction (EIB). Three studies assessing the effect of vitamin C on patients with EIB were subjected to a meta-analysis and revealed that vitamin C reduced postexercise FEV1 decline by 48% (95% CI: 33% to 64%). The correlation between postexercise FEV1 decline and respiratory symptoms associated with exercise is poor, yet symptoms are the most relevant to patients. Five other studies examined subjects who were under short-term, heavy physical stress and revealed that vitamin C reduced the incidence of respiratory symptoms by 52% (95% CI: 36% to 65%). Another trial reported that vitamin C halved the duration of the respiratory symptoms in male adolescent competitive swimmers. Although FEV1 is the standard outcome for assessing EIB, other outcomes may provide additional information. In particular, the mean postexercise decline of FEF50 is twice the decline of FEV1. Schachter and Schlesinger (1982) reported the effect of vitamin C on exercise-induced FEF60 levels in 12 patients suffering from EIB and their data are analyzed in this paper. The postexercise FEF60 decline was greater than 60% for five participants and such a dramatic decline indicates that the absolute postexercise FEF60 level becomes an important outcome in its own right. Vitamin C increased postexercise FEF60 levels by 50% to 150% in those five participants, but had no significant effect in the other seven participants. Thus, future research on the effects of vitamin C on EIB should not be restricted to measuring only FEV1. Vitamin C is inexpensive and safe, and further study on those people who have EIB or respiratory symptoms associated with exercise is warranted.

Most studies that have evaluated the association between anti-diabetic medication and cancer risk have suffered from methodological drawbacks. To avoid time-related biases, we evaluated the effect of treatment duration on the cancer risk among naive users of anti-diabetic medication as compared to non-users. In addition, we addressed the influence of common risk factors such as smoking and BMI. The study population comprised 23,394 participants of FINRISK surveys. Data on cancer and anti-diabetic medication were linked with the study cohorts. We applied Lexis tabulation to the data and analyzed split records by using Poisson regression. Changes in cancer incidence in relation to treatment duration were examined by modeling the rate ratio (RR). After a median follow-up of 9 years, 53 cancer cases among users of anti-diabetic medication and 1,028 among non-users were diagnosed. No significant difference in cancer risk between users and non-users was observed after adjustment. The RR for all medication regardless of its duration was 1.01 [95% CI 0.75–1.33], and 1.37 [0.94–1.94] for period of 1–4 years. The results were similar for metformin, sulfonylurea, and insulin. This study demonstrates that evaluation of the variation in cancer risk in relation to treatment duration is of particular importance for enhancing the accuracy of conclusions on the link between exposure to anti-diabetic medication and cancer risk.

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Background To estimate cardiovascular disease (CVD) mortality in relation to obesity and gender. Methods Data from 11 prospective cohorts from four European countries including 23 629 men and 21 965 women, aged 24 to 99 years, with a median follow-up of 7.9 years were analyzed. Hazards ratios (HR) for CVD mortality in relation to baseline body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were estimated using Cox proportional hazards models with age as the timescale. Results Men had higher CVD mortality than women in all four BMI categories (

Dear Editor, Lee et al.1) carried out a meta-analysis of the potential role of exercise in preventing the common cold, and calculated that exercise might reduce the incidence of colds by 27% (relative risk [RR], 0.73; 95% confidence interval [CI], 0.56 to 0.95). However, their study has important limitations. First, one of the four included trials was a study by Chubak et al.2) although I pointed out that the total number of upper respiratory tract infections did not differ between the exercise and control groups in that study.3) Thus, although the incidence of less severe upper respiratory infections ('the common cold') was lower in the exercise group, the incidence of more severe respiratory tract infections (such as 'flu') was higher. The difference in the distribution of the severity of respiratory infections between the control and exercise groups was highly significant with P = 0.0004.3) Thus, exercise might, in fact, have caused harm by making respiratory infections more severe, without influencing their total incidence. Thus, by presenting the data for only the less severe respiratory infections ('common colds') of the Chubak et al.'s study, Lee et al. mislead the reader. Second, Lee et al.1) ignored our large cohort study which found that physical activity at work, and at leisure, had no association with the common cold risk when adjusted for potential confounders.4) We analyzed the relationship between leisure time physical activity and common cold incidence in 3,470 males who were followed up for 2 years. In contrast, the meta-analysis by Lee et al.1) included only 281 participants. Therefore, our study had much narrower CIs. For example, compared with the sedentary participants (n = 1,198), those who carried out moderate-level physical activity at leisure 3 times per week (n = 268) had a slightly higher incidence of colds with adjusted RR (1.05; 95% CI, 0.96 to 1.16).4) Such a narrow CI around the null effect is inconsistent with any substantial reduction in common cold incidence by moderate level exercise. Finally, even if Lee's estimate for the effect of exercise on common cold risk is valid (RR = 0.73), such an effect has no practical importance. Given that adults usually have 2 to 4 colds per year,5) an average person should exercise for 1 to 2 years to prevent 1 episode of the common cold on the basis of the RR = 0.73 estimate. Lee et al.1) indicated that regular exercise means having exercise sessions 5 times per week. Assuming that 1 exercise session takes 1 hour, 5 exercise sessions per week for 1 year sums up to 250 hours in total; corresponding to 10 full days. Thus, with an effect of RR = 0.73 a person should exercise a time period corresponding to over 1 week round the clock to prevent 1 episode of the common cold which usually does not last over 1 week and usually only slightly limits functional activities. Thus, more time would be used in the exercise sessions than would be saved from suffering from the cold symptoms. Exercise has a number of beneficial effects and therefore sedentary people should be encouraged to start exercise. However, there is no good evidence that exercise reduces the risk of colds. Exercise should not be encouraged with the argument that it would reduce the risk of colds. Yours Sincerely

MiRNAs are fine-tuning modifiers of skeletal muscle regulation, but knowledge of their hormonal control is lacking. We used a co-twin case-control study design, that is, monozygotic postmenopausal twin pairs discordant for estrogen-based hormone replacement therapy (HRT) to explore estrogen-dependent skeletal muscle regulation via miRNAs. MiRNA profiles were determined from vastus lateralis muscle of nine healthy 54-62-years-old monozygotic female twin pairs discordant for HRT (median 7 years). MCF-7 cells, human myoblast cultures and mouse muscle experiments were used to confirm estrogen's causal role on the expression of specific miRNAs, their target mRNAs and proteins and finally the activation of related signaling pathway. Of the 230 miRNAs expressed at detectable levels in muscle samples, qPCR confirmed significantly lower miR-182, miR-223 and miR-142-3p expressions in HRT using than in their nonusing co-twins. Insulin/IGF-1 signaling emerged one common pathway targeted by these miRNAs. IGF-1R and FOXO3A mRNA and protein were more abundantly expressed in muscle samples of HRT users than nonusers. In vitro assays confirmed effective targeting of miR-182 and miR-223 on IGF-1R and FOXO3A mRNA as well as a dose-dependent miR-182 and miR-223 down-regulations concomitantly with up-regulation of FOXO3A and IGF-1R expression. Novel finding is the postmenopausal HRT-reduced miRs-182, miR-223 and miR-142-3p expression in female skeletal muscle. The observed miRNA-mediated enhancement of the target genes' IGF-1R and FOXO3A expression as well as the activation of insulin/IGF-1 pathway signaling via phosphorylation of AKT and mTOR is an important mechanism for positive estrogen impact on skeletal muscle of postmenopausal women.

Research suggests autoimmune processes to be involved in psychiatric disorders. We aimed to address the prevalence and incidence of autoimmune diseases in a large Finnish patient cohort with anorexia nervosa, bulimia nervosa, and binge eating disorder. Methods Patients (N = 2342) treated at the Eating Disorder Unit of Helsinki University Central Hospital between 1995 and 2010 were compared with general population controls (N = 9368) matched for age, sex, and place of residence. Data of 30 autoimmune diseases from the Hospital Discharge Register from 1969 to 2010 were analyzed using conditional and Poisson regression models. Results Of patients, 8.9% vs. 5.4% of control individuals had been diagnosed with one or more autoimmune disease (OR 1.7, 95% CI 1.5–2.0, P

Governances, structures and contents of mental health services are being reformed across countries. There is a need for data to support those changes. The aim of this study was to explore the quality, i.e., diversity and community orientation, and quantity, i.e., personnel resources, of mental health and substance abuse services (MHS) and evaluate correlation between population needs and quality and quantity of MHS. The European Service Mapping Schedule—Revised (ESMS-R) was used to classify mental health and substance abuse services in southern Finland. Municipal-level aggregate data, local data on unemployment rate, length of education, age of retirement, proportion of single households, alcohol sales and a composite mental health index were used as indicators of population mental health needs. Population size correlated strongly with service diversity, explaining 84% of the variance. Personnel resources did not associate with diversity or community orientation. The indicators of mental health services need did not have the expected association with quality and quantity of services. In terms of service organization, the results may support larger population bases, at least 150,000 adult inhabitants, when aiming for higher diversity. © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)

Correction: Volume: 349 Article Number: g4921 DOI: 10.1136/bmj.g4921 OBJECTIVE: To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications. DESIGN: Cohort of protocols of randomised controlled trial and subsequent full journal publications. SETTING: Six research ethics committees in Switzerland, Germany, and Canada. DATA SOURCES: 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications. RESULTS: Of 894 protocols of randomised controlled trials, 252 (28.2%) included one or more planned subgroup analyses. Of those, 17 (6.7%) provided a clear hypothesis for at least one subgroup analysis, 10 (4.0%) anticipated the direction of a subgroup effect, and 87 (34.5%) planned a statistical test for interaction. Industry sponsored trials more often planned subgroup analyses compared with investigator sponsored trials (195/551 (35.4%) v 57/343 (16.6%), P

High throughput sequencing (HTS) generates large amounts of high quality sequence data for microbial genomics. The value of HTS for microbial forensics is the speed at which evidence can be collected and the power to characterize microbial-related evidence to solve biocrimes and bioterrorist events. As HTS technologies continue to improve, they provide increasingly powerful sets of tools to support the entire field of microbial forensics. Accurate, credible results allow analysis and interpretation, significantly influencing the course and/or focus of an investigation, and can impact the response of the government to an attack having individual, political, economic or military consequences. Interpretation of the results of microbial forensic analyses relies on understanding the performance and limitations of HTS methods, including analytical processes, assays and data interpretation. The utility of HTS must be defined carefully within established operating conditions and tolerances. Validation is essential in the development and implementation of microbial forensics methods used for formulating investigative leads attribution. HTS strategies vary, requiring guiding principles for HTS system validation. Three initial aspects of HTS, irrespective of chemistry, instrumentation or software are: 1) sample preparation, 2) sequencing, and 3) data analysis. Criteria that should be considered for HTS validation for microbial forensics are presented here. Validation should be defined in terms of specific application and the criteria described here comprise a foundation for investigators to establish, validate and implement HTS as a tool in microbial forensics, enhancing public safety and national security. Published version

Exome sequencing studies in complex diseases are challenged by the allelic heterogeneity, large number and modest effect sizes of associated variants on disease risk and the presence of large numbers of neutral variants, even in phenotypically relevant genes. Isolated populations with recent bottlenecks offer advantages for studying rare variants in complex diseases as they have deleterious variants that are present at higher frequencies as well as a substantial reduction in rare neutral variation. To explore the potential of the Finnish founder population for studying low-frequency (0.5–5%) variants in complex diseases, we compared exome sequence data on 3,000 Finns to the same number of non-Finnish Europeans and discovered that, despite having fewer variable sites overall, the average Finn has more low-frequency loss-of-function variants and complete gene knockouts. We then used several well-characterized Finnish population cohorts to study the phenotypic effects of 83 enriched loss-of-function variants across 60 phenotypes in 36,262 Finns. Using a deep set of quantitative traits collected on these cohorts, we show 5 associations (p, National Institutes of Health (U.S.) (NIH RC2 HL-102925)

Objectives The aim of this study was twofold: to investigate socioeconomic differences in disability retirement (DR) due to major diseases and find out which diseases contribute most to the overall socioeconomic differences in DR. Methods The data were longitudinal register-based (10% sample of Finns) from Statistics Finland. These data included 258 428 participants aged 35–64 years during the follow-up. The participants were employed or unemployed before the follow-up period 1997–2010. Of all participants, 14 303 men and 13 188 women ended up in DR during the follow-up. Socioeconomic status was categorized into upper- and lower-class non-manual employees, manual workers, and self-employed persons. Cox models were used to estimate hazard ratios for DR due to different diseases. Results Compared to upper-class non-manual employees, DR was especially high for manual workers whose retirement diagnoses included psychoactive substance use, musculoskeletal diseases (MSD), or cardiovascular diseases. Socioeconomic differences in DR were stronger for younger age groups and men versus women. For females and males, the largest part of the excess DR among manual workers compared to upper-class non-manual employees was due to MSD. In the age group 54–64 years, the contribution of MSD to the total excess was >50% among male manual workers and 75% among female manual workers. Excess DR due to mental disorders concerned only 35–54-year-old manual workers (among 23% men and 26% women). Conclusion The contribution of MSD to the total excess DR among lower socioeconomic groups was large. Prevention of MSD among manual workers would likely reduce socioeconomic differences in DR.

Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized. Electronic supplementary material The online version of this article (doi:10.1007/s10519-014-9654-x) contains supplementary material, which is available to authorized users.

Background Common mental disorders (CMD) are prevalent in working populations and have adverse consequences for employee well-being and work ability, even leading to early retirement. Several studies report associations between psychosocial working conditions and CMD. However, there is a lack of longitudinal research within a broad framework of psychosocial working conditions and improvement in CMD. The aim of this study was to examine the associations between several psychosocial working conditions and deteriorating and improving CMD among ageing employees over a five-to-six-year follow-up period. Methods The study is based on the Helsinki Health Study baseline survey in 2001–2002 and a follow-up in 2007 (N = 4340, response rate 83%) conducted among 40-60-year-old female and male employees. The General Health Questionnaire (GHQ-12) was used to measure common mental disorders. Psychosocial working conditions were measured in terms of job strain, organisational justice, work-family interface, social support and workplace bullying. The covariates included sociodemographic and health factors. Results Following adjustment for all the covariates, family-to-work (OR 1.41, 95% Cl 1.04-1.91) and work-to-family conflicts (OR 1.99, 95% Cl 1.42-2.78) and workplace bullying (OR 1.40, 95% Cl 1.09-1.79) were associated with deterioration, and family-to-work conflicts (OR 1.65, 95% Cl 1.66-2.34) and social support (OR 1.47, 95% Cl 1.07-2.00) with improvement in CMD. Conclusions Adverse psychosocial working conditions contribute to poor mental health among employees. Preventing workplace bullying, promoting social support and achieving a better balance between work and family may help employees to maintain their mental health.

Coronary artery disease (CAD) is a complex disease driven by myriad interactions of genetics and environmental factors. Traditionally, studies have analyzed only one disease factor at a time, providing useful but limited understanding of the underlying etiology. Recent advances in cost-effective and high-throughput technologies, such as single nucleotide polymorphism (SNP) genotyping, exome/genome sequencing, gene expression microarrays and metabolomics assays have enabled the collection of millions of data points in many thousands of individuals. In order to make sense of such 'omics' data, effective analytical methods are needed. We review and highlight some of the main results in this area, focusing on integrative approaches that consider multiple modalities simultaneously. Such analyses have the potential to uncover the genetic basis of CAD, produce genomic risk scores (GRS) for disease prediction, disentangle the complex interactions underlying disease, and predict response to treatment.

BACKGROUND: Many patients and healthcare professionals believe that work-related psychosocial stress, such as job strain, can make asthma worse, but this is not corroborated by empirical evidence. We investigated the associations between job strain and the incidence of severe asthma exacerbations in working-age European men and women. METHODS: We analysed individual-level data, collected between 1985 and 2010, from 102 175 working-age men and women in 11 prospective European studies. Job strain (a combination of high demands and low control at work) was self-reported at baseline. Incident severe asthma exacerbations were ascertained from national hospitalization and death registries. Associations between job strain and asthma exacerbations were modelled using Cox regression and the study-specific findings combined using random-effects meta-analyses. RESULTS: During a median follow-up of 10 years, 1 109 individuals experienced a severe asthma exacerbation (430 with asthma as the primary diagnostic code). In the age- and sex-adjusted analyses, job strain was associated with an increased risk of severe asthma exacerbations defined using the primary diagnostic code (hazard ratio, HR: 1.27, 95% confidence interval, CI: 1.00, 1.61). This association attenuated towards the null after adjustment for potential confounders (HR: 1.22, 95% CI: 0.96, 1.55). No association was observed in the analyses with asthma defined using any diagnostic code (HR: 1.01, 95% CI: 0.86, 1.19). CONCLUSIONS: Our findings suggest that job strain is probably not an important risk factor for severe asthma exacerbations leading to hospitalization or death.

Introduction Social determinants of health have not been intensively studied in Russia, even though the health divide has been clearly demonstrated by an increased mortality rate among those with low education. A comparative analysis of social health determinants in countries with different historical and economic backgrounds may provide useful evidence for addressing health inequalities. We aimed to assess socioeconomic determinants of self-rated health in St. Petersburg as compared to Estonia and Finland. Methods Data for women aged 18–44 were extracted from existing population-based surveys and analysed. In St. Petersburg the data were originally collected in 2003 (response rate 68%), in Estonia in 2004–2005 (54%), and in Finland in 2000–2001 (86%). The study samples comprised 865 women in St. Petersburg, 2141 in Estonia and 1897 in Finland. Results Self-rated health was much poorer in St. Petersburg than in Estonia or Finland. High education was negatively associated with poor self-rated health in all the studied populations; it was (partially) mediated via health behaviour and limiting long-term illness only in Estonia and Finland, but not in St. Petersburg. High personal income and employment did not associate with poor self-rated health among St. Petersburg women, as it did in Estonia and Finland. In St. Petersburg housewives rather than employed women had better self-rated health, unlike the two other areas. Conclusion Women’s self-rated health in St. Petersburg varied similarly by education but differently by income and employment as compared to Estonia and Finland. Education is likely the most meaningful dimension of women’s socioeconomic position in St. Petersburg. More research is needed to further clarify the pathways between socioeconomic position and health in Russia.

Length and weight in infancy are associated with neurodevelopment, but less is known about growth in other anthropometric measures. In this study we analyzed how the development in length, weight, head circumference, and chest circumference over infancy is associated with motor development in early childhood, using a twin study design. Information on physical development over infancy and the age at achievement of eight developmental milestones over early childhood was collected for 370 Japanese twin pairs. Linear mixed models were used to analyze how physical development is associated with motor development between individual twins, as well as within twin pairs, adjusting the results for shared maternal and postnatal environmental factors. Delayed motor development was associated with smaller body size over infancy, and we also found some suggestive evidence that it was associated with catch-up growth as well. When studying the associations within twin pairs discordant for motor development, similar associations were found. However, chest circumference showed the most robust association within discordant twin pairs. Smaller body size and rapid catch-up growth are associated with delayed motor development. When studying these associations within twin pairs and thus adjusting the results for gestational age as well as many other maternal and postnatal environmental factors, chest circumference showed the most robust association. Chest circumference, rarely used in developed countries, can offer additional information on prenatal conditions relevant for further motor development not achieved by more traditional anthropometric measures.