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Background We sought to clarify the impact of adolescent alcohol misuse on adult physical health and subjective well-being. To do so, we investigated both the direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction and the indirect effects on these outcomes attributable to subsequent alcohol problems. Method The sample included 2733 twin pairs (32% monozygotic; 52% female) from the FinnTwin16 study. Adolescent alcohol misuse was a composite of frequency of drunkenness, frequency of alcohol use, and alcohol problems at ages 16, 17, and 18.5. The early midlife outcomes included somatic symptoms, self-rated health, and life satisfaction at age 34. The mediators examined as part of the indirect effect analyses included alcohol problems from the Rutgers Alcohol Problem Index at ages 24 and 34. Serial mediation and co-twin comparison models were applied and included covariates from adolescence and early midlife. Results There were weak direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction. However, there was stronger evidence for indirect effects, whereby young adult and early midlife alcohol problems serially mediated the relationship between adolescent alcohol misuse and early midlife somatic symptoms (beta = 0.03, 95% CI [0.03, 0.04]), self-rated health (beta = -0.02, 95% CI [-0.03, -0.01]), and life satisfaction (beta = -0.03, CI [-0.04, -0.02]). These serial mediation effects were robust in co-twin comparison analyses. Conclusions These results provide evidence that alcohol problems are a primary driver linking adolescent alcohol misuse and poor health outcomes across the lifespan.

Background The heritability of traits such as body mass index (BMI), a measure of obesity, is generally estimated using family and twin studies, and increasingly by molecular genetic approaches. These studies generally assume that genetic effects are uniform across all trait values, yet there is emerging evidence that this may not always be the case. Method/Subjects This paper analyzes twin data using a recently developed measure of heritability called the heritability curve. Under the assumption that trait values in twin pairs are governed by a flexible Gaussian mixture distribution, heritability curves may vary across trait values. The data consist of repeated measures of BMI on 1506 monozygotic (MZ) and 2843 like-sexed dizygotic (DZ) adult twin pairs, gathered from multiple surveys in older Finnish Twin Cohorts. Results The heritability curve and BMI value-specific MZ and DZ pairwise correlations were estimated, and these varied across the range of BMI. MZ correlations were highest at BMI values from 21 to 24, with a stronger decrease for women than for men at higher values. Models with additive and dominance effects fit best at low and high BMI values, while models with additive genetic and common environmental effects fit best in the normal range of BMI. Conclusions We demonstrate that twin and molecular genetic studies need to consider how genetic effects vary across trait values. Such variation may reconcile findings of traits with high heritability and major differences in mean values between countries or over time.

Obesity is considered an important global public health challenge, and its prevalence is rapidly increasing in children. We investigated in this study if the upper-normal TSH level may be associated with metabolic syndrome parameters, including obesity, high blood pressure, and dyslipidemia and changes in insulin sensitivity in overweight and obese children. We also investigated whether there is a relationship between BMI and these parameters. This prospective case-control study comprised 145 participants (74 females, 71 males) aged 5–18 years. Participants were divided into three groups according to their BMI z-score, as overweight, obese and control. The control group included 35 age and sex-matched healthy subjects. Thyroid stimulating hormone levels of control, overweight and obese groups were 2.14 ± 1.27, 2.97 ± 1.26 and 3.13 ± 1.11, respectively (p

Aim: To investigate the relationship between the eccentricity of the body as a function of mass, height, circumference and body mass index of the body in the section of equal torques of the upper and lower part of body. Results: 62 people between the age of 18 and 28 were examined. Very good correlations between the eccentricity of the equal torques of the upper and lower parts of the body and body mass, height, BMI and circumference of the body in the section were derived. We were hypothesized that the cross section of equal torques is an area in which all body movements are focused. We are considering this area as "kinetic center" of the body. As proof of the reality of this center it was point out the infrared photos of the human body. The position of the ‘kinetic center’ on infrared body image appears point on spinal cord with highest temperature. Conclusions: The obtained results can find applications in solving various scientific problems.

Introduction: Using data from the TackSHS survey, we aim to provide updated estimates on the prevalence and determinants of overweight and obesity in Europe. Methods: A face-to-face survey was conducted in 2017–2018 in 12 European countries (Bulgaria, England, France, Germany, Greece, Ireland, Italy, Latvia, Poland, Portugal, Romania, and Spain). Overall, 10,810 participants, representative in each country of the general adult population, provided information on self-reported height and weight. Results: Almost half of participants (48.1%; 95% confidence interval, CI: 47.2–49.1) reported to be overweight or obese (54.1% in men and 42.5% in women) and 12.6% (95% CI: 12.0–13.2) obese (11.3% in men and 13.8% in women). Obesity prevalence was lowest in Italy (7.5%) and France (8.8%) and highest in Greece (19.7%) and Romania (21.1%). Multilevel logistic random-effects analyses showed that prevalence of obesity was related with higher age and lower level of education and socioeconomic status. As compared to northern European countries, Western and Southern European ones showed a significantly lower obesity prevalence. When compared to a companion study conducted in 2010, Eastern and Northern European countries showed an increased trend in obesity prevalence. Conversely, countries with the lowest obesity prevalence (less than 10%), such as Italy and France, showed a decreased trend. Conclusions: Despite a large heterogeneity across countries, overweight and obesity prevalence estimates in Europe are alarming, with most of the countries reporting obesity prevalence approaching 20% or more, particularly in Eastern and Northern Europe. Since 2010, obesity prevalence increased in most of these countries.

Although the composition and functional potential of the human gut microbiota evolve over the lifespan, kinship has been identified as a key covariate of microbial community diversification. However, to date, sharing of microbiota features within families has mostly been assessed between parents and their direct offspring. Here we investigate the potential transmission and persistence of familial microbiome patterns and microbial genotypes in a family cohort (n = 102) spanning 3 to 5 generations over the same female bloodline. We observe microbiome community composition associated with kinship, with seven low abundant genera displaying familial distribution patterns. While kinship and current cohabitation emerge as closely entangled variables, our explorative analyses of microbial genotype distribution and transmission estimates point at the latter as a key covariate of strain dissemination. Highest potential transmission rates are estimated between sisters and mother–daughter pairs, decreasing with increasing daughter’s age and being higher among cohabiting pairs than those living apart. Although rare, we detect potential transmission events spanning three and four generations, primarily involving species of the genera Alistipes and Bacteroides. Overall, while our analyses confirm the existence of family-bound microbiome community profiles, transmission or co-acquisition of bacterial strains appears to be strongly linked to cohabitation., Quantitative metagenomic analyses of gut microbiomes reveals kinship, together with current cohabitation, as drivers of microbial community transmission and persistence between family members over three to five generations.

Objective:To explore the relationships between dental problems and underweight status among rural women in Burkina Faso by using nationally representative data.Design:This was a cross-sectional secondary study of primary data obtained by the 2013 WHO Stepwise Approach to Surveillance survey conducted in Burkina Faso. Descriptive and analytical analyses were performed using Student’s t test, ANOVA, the χ2 test, Fisher’s exact test and logistic regression.Setting:All thirteen Burkinabè regions were categorised using quartiles of urbanisation rates.Participants:The participants were 1730 rural women aged 25–64 years.Results:The prevalence of underweight was 16·0 %, and 24·1 % of participants experienced dental problems during the 12-month period. The women with dental problems were more frequently underweight (19·9 % and 14·7 %; P < 0·05) and had a lower mean BMI (21·1 ± 3·2 and 21·6 ± 3·7 kg/m2, P < 0·01) than those without dental problems. More risk factors for underweight were observed in less urbanised regions among elderly individuals (> 49 years old) and smokeless tobacco users. Age > 49 years, professions with inconsistent income, a lack of education, smokeless tobacco use and low BMI were factors that were significantly associated with dental problems, while residency in a low-urbanisation area was a protective factor.Conclusion:The prevalence of underweight in rural Burkinabè women is among the highest in sub-Saharan Africa, and women with dental problems are more frequently affected than those without dental problems. Public health measures for the prevention of these disorders should specifically target women aged over 49 years and smokeless tobacco users.

BackgroundFat deposition is associated with adverse outcomes. Waist-to-hip (WHR) ratio is a simple feasible index to assess fat distribution. Lipoprotein particle composition in relation to WHR and to what extent their association is mediated by insulin sensitivity are less investigated.MethodsIn 504 randomly recruited Flemish (mean age: 48.9 years; women: 51.6%), we analyzed the lipoprotein particle constitutions using nuclear magnetic resonance spectroscopy. WHR obesity described a WHR of ≥ 0.85 for women or 0.9 for men. Insulin sensitivity was evaluated by the homeostasis model assessment-estimated insulin resistance (HOMA-IR). SCORE-2 risk algorithm was applied to estimate 10-year cardiovascular risk. Statistical methods included multivariable-adjusted linear regression analysis, logistic regression analysis, and mediation analysis.ResultsThe prevalence of WHR obesity was 54.6%, approximately 3 times of BMI-determined obesity (19.1%). Individuals with WHR obesity had significantly higher metabolic complications, such as hypertension (57.1%), dyslipidemia (61.8%), and insulin resistance (14.2%). WHR and WHR obesity were positively associated with total very-low-density lipoprotein (VLDL) particle concentration, remnant cholesterol, and triglycerides, but were negatively associated with VLDL particle size (P ≤ 0.027), independent of body mass index and other covariates. WHR was inversely associated with total high-density lipoprotein (HDL) particle concentration, whereas WHR obesity was inversely associated with HDL cholesterol (P ≤ 0.039). Neither WHR nor WHR obesity was associated with the concentration of total low-density lipoprotein (LDL) particles, LDL particle size, and LDL cholesterol (P ≥ 0.089). In the mediation analysis, insulin sensitivity significantly mediated the effect of WHR on total VLDL particle concentration (mediation percentage: 37.0%), remnant cholesterol (47.7%), and HDL cholesterol (41.1%). Individuals with WHR obesity were at increased cardiovascular risk, regardless of LDL cholesterol (P ≤0.028). In WHR obesity, higher total VLDL particle concent36ration and remnant cholesterol, and lower HDL cholesterol were associated with an increased cardiovascular risk (P≤ 0.002).ConclusionsUpper-body fat deposition was independently associated with an unfavorable lipoprotein profile, and insulin sensitivity significantly mediated this association. LDL cholesterol might underestimate lipid abnormality for people with upper-body obesity and lowering VLDL particles and remnant cholesterol might potentially reduce the residual cardiovascular risk.

We propose a model for obesity development that traces a considerable part of its origins to the social domain (mainly different forms of prolonged social adversity), both within and across generations, working in tandem with a genetic predisposition. To facilitate overview of social pathways, we place particular focus on three areas that form a cascading sequence: (A) social adversity within the family (parents having a low education, a low social position, poverty and financial insecurity; offspring being exposed to gestational stress, unmet social and emotional needs, abuse, maltreatment and other negative life events, social deprivation and relationship discord); (B) increasing levels of insecurity, negative emotions, chronic stress, and a disruption of energy homeostasis; and (C) weight gain and obesity, eliciting further social stress and weight stigma in both generations. Social adversity, when combined with genetic predisposition, thereby substantially contributes to highly effective transmission of obesity from parents to offspring, as well as to obesity development within current generations. Prevention efforts may benefit from mitigating multiple types of social adversity in individuals, families, and communities, notably poverty and financial strain, and by improving education levels.

Background: To investigate the possible associations between childhood noninfectious uveitis and cardio-respiratory fitness, physical activity, health related quality of life and fatigue. Methods: Cross-sectional analysis of 23 patients with noninfectious uveitis, aged 8-18 years. BMI, exercise capacity, muscle strength and physical activity were measured. Health-related quality of life and fatigue were assessed. The results were compared to standardized values for age matched healthy children. Results: Twenty-three patients were included. Children with uveitis had a higher bodyweight and body mass index. Children with uveitis had lower cardio-respiratory fitness and they were less physically active, but they experienced a normal quality of life and normal fatigue. Parents of children with uveitis reported a lower quality of life and more fatigue for their children than parents of healthy children. Conclusion: Our study indicates that children with noninfectious uveitis are at risk of developing lower physical and psychosocial health.

Summary: Individuals with low socio-economic status (SES) have a more than 25% higher risk of fragility fractures than individuals with high SES. Body mass index and lifestyle appear to mediate the effect of SES on fracture risk. Strategies to prevent fractures should aim to reduce unhealthy behaviours through tackling structural inequalities. Introduction: This systematic review and meta-analysis aimed to evaluate the impact of socio-economic status (SES) on fragility fracture risk. Methods: Medline, Embase, and CINAHL databases were searched from inception to 28 April 2021 for studies reporting an association between SES and fragility fracture risk among individuals aged ≥50 years. Risk ratios (RR) were combined in meta-analyses using random restricted maximum likelihood models, for individual-based (education, income, occupation, cohabitation) and area-based (Index of Multiple Deprivation, area income) SES measures. Results: A total of 61 studies from 26 different countries including more than 19 million individuals were included. Individual-based low SES was associated with an increased risk of fragility fracture (RR 1.27 [95% CI 1.12, 1.44]), whilst no clear association was seen when area-based measures were used (RR 1.08 [0.91, 1.30]). The strength of associations was influenced by the type and number of covariates included in statistical models: RR 2.69 [1.60, 4.53] for individual-based studies adjusting for age, sex and BMI, compared with RR 1.06 [0.92, 1.22] when also adjusted for health behaviours (smoking, alcohol, and physical activity). Overall, the quality of the evidence was moderate. Conclusion: Our results show that low SES, measured at the individual level, is a risk factor for fragility fracture. Low BMI and unhealthy behaviours are important mediators of the effect of SES on fracture risk. Strategies to prevent fractures and reduce unhealthy behaviours should aim to tackle structural inequalities in society thereby reducing health inequalities in fragility fracture incidence.

Objectives: Obesity is associated with increased risk of depression, but the extent to which this association is symptom-specific is unknown. We examined the associations of overweight and obesity with individual depressive symptoms. Methods: We pooled data from 15 population-based cohorts comprising 57,532 individuals aged 18 to 100 years at study entry. Primary analyses were replicated in an independent cohort, the UK Biobank study (n = 122,341, age range 38 to 72). Height and weight were assessed at baseline and body mass index (BMI) was computed. Using validated self-report measures, 24 depressive symptoms were ascertained once in 16 cross-sectional, and twice in 7 prospective cohort studies (mean follow-up 3.2 years). Results: In the pooled analysis of the primary cohorts, 22,045 (38.3 %) participants were overweight (BMI between 25 and 29.9 kg/m(2)), 12,025 (20.9 %) class I obese (BMI between 30 and 34.9 kg/m(2)), 7,467 (13.0 %) class II-III obese (BMI >= 35 kg/m(2)); and 7,046 (12.3 %) were classified as depressed. After multivariable adjustment, obesity class I was cross-sectionally associated with 1.11-fold (95 % confidence interval 1.01-1.22), and obesity class II-III with 1.31-fold (1.16-1.49) higher odds of overall depression. In symptom-specific analyses, robust associations were apparent for 4 of the 24 depressive symptoms ('could not get going/lack of energy', 'little interest in doing things', 'feeling bad about yourself, and 'feeling depressed'), with confounder-adjusted odds ratios of having 3 or 4 of these symptoms being 1.32 (1.10-1.57) for individuals with obesity class I, and 1.70 (1.34-2.14) for those with obesity class II-III. Elevated C-reactive protein and 21 obesity-related diseases explained 23 %-31 % of these associations. Symptom-specific associations were confirmed in longitudinal analyses where obesity preceded symptom onset, were stronger in women compared with men, and were replicated in UK Biobank. Conclusions: Obesity is associated with a distinct set of depressive symptoms. These associations are partially explained by systemic inflammation and obesity-related morbidity. Awareness of this obesity-related symptom profile and its underlying biological correlates may inform better targeted treatments for comorbid obesity and depression.

Objectives There are studies on associations between obesity and mortality in nursing home (NH) residents, but the presence of concomitant muscle weakness has not been examined. We considered that self-reported weakness might be a low muscle strength proxy marker. We aimed to examine associations of obesity alone, self-reported muscle weakness alone, and their combination with mortality in NH residents. Methods This is a retrospective longitudinal follow-up study. We noted age, sex, nutritional status, functionality, number of chronic diseases, and regular medication. Obesity was assessed by the body fat-percentage method estimated by bioimpedance analysis. Weakness was identified by self-reported muscle weakness. Survival was evaluated with a univariate log-rank test and multivariate Cox regression analyses. Results We included 214 participants. In a median follow-up time of 46 months, mortality occurred in 37.4%. In multivariate analysis adjusted by age, sex, undernutrition, number of chronic diseases, and regular medication, functional scores; \"non-weak non-obese\" participants or \"weak alone\" participants or \"weak+obese\" participants had higher mortality risk when compared with the \"obesity alone\" participants [hazard ratio (HR) = 2.6, 95% confidence interval (CI) = 1.2-5.5, p = 0.01; HR = 2.6, 95% CI = 1.2-5.9, p = 0.02; HR = 3.0, 95% CI = 1.2-7.7, p = 0.02]. Conclusion This is the first report showing that obesity was associated with lower mortality risk if the weakness was not present in NH residents. However, obesity with concomitant weakness was associated with mortality risk similar to non-weak non-obese or weak alone participants. Our study suggests a simple consideration of weakness that can easily be integrated into everyday practice.

PERMUTE: et al., Studies in genetically ‘identical’ individuals indicate that as much as 50% of complex trait variation cannot be traced to genetics or to the environment. The mechanisms that generate this ‘unexplained’ phenotypic variation (UPV) remain largely unknown. Here, we identify neuronatin (NNAT) as a conserved factor that buffers against UPV. We find that Nnat deficiency in isogenic mice triggers the emergence of a bi-stable polyphenism, where littermates emerge into adulthood either ‘normal’ or ‘overgrown’. Mechanistically, this is mediated by an insulin-dependent overgrowth that arises from histone deacetylase (HDAC)-dependent β-cell hyperproliferation. A multi-dimensional analysis of monozygotic twin discordance reveals the existence of two patterns of human UPV, one of which (Type B) phenocopies the NNAT-buffered polyphenism identified in mice. Specifically, Type-B monozygotic co-twins exhibit coordinated increases in fat and lean mass across the body; decreased NNAT expression; increased HDAC-responsive gene signatures; and clinical outcomes linked to insulinemia. Critically, the Type-B UPV signature stratifies both childhood and adult cohorts into four metabolic states, including two phenotypically and molecularly distinct types of obesity., This work was supported by funding from the MPG, the VAI, the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 675610, the Novo Nordisk Foundation, European Foundation for the Study of Diabetes and the Danish Council for Independent Research and National Institutes of Health awards R21HG011964 and 1R01HG012444. The LCAT cohort was supported by grants from AK German Research Foundation CRC1052 (no. 209933838), project C05 and KO3512/3-1, the German Diabetes Association and the Federal Ministry of Education and Research, Germany, FKZ, 01EO1001 (Integrated Research and Treatment Center Adiposity Diseases). TwinsUK is funded by the Wellcome Trust, Medical Research Council, European Union, Chronic Disease Research Foundation, Zoe Global Ltd. and the National Institute for Health Research-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London.

Context Early growth is associated with childhood adiposity, but the influence of lifestyle remains unknown. Objective This work aimed to investigate the association of growth profiles from high-risk pregnancies with adiposity at age 5 years, taking into account lifestyle and several antenatal/postnatal exposures. Methods This prospective cohort study included 609 children born during the Finnish Gestational Diabetes Prevention Study (RADIEL), recruiting women with body mass index (BMI) greater than or equal to 30 and/or prior gestational diabetes mellitus (GDM) (2008-2013). Altogether 332 children attended the 5-year follow-up (2014-2017). Main outcome measures included growth profiles based on ponderal index (PI = weight/height3), investigated using latent class mixed models. Adiposity was assessed with anthropometrics and body composition (InBody720). Results We identified 3 growth profiles: ascending (n = 82), intermediate (n = 351), and descending (n = 149). Children with ascending growth had a higher body fat percentage, ISO-BMI, and waist circumference (P Conclusion Accelerated early growth was associated with higher adiposity in 5-year-old children from high-risk pregnancies, even when adjusted for lifestyle. Reducing cesarean deliveries and promoting breastfeeding may be beneficial for postnatal growth.

Background Advanced maternal age and obesity are associated with impaired female fertility. Moreover, fatty acids (FA) in follicular fluid (FF) play important roles in oocyte maturation and embryo development. However, the effects of body mass index (BMI), age, and FF FA composition on embryo development between days 3 and 5 and blastocyst stage on day 5 are still unclear. Methods This study included 138 patients undergoing assisted reproductive technology (ART), which were divided into three BMI groups (18.5–24.9 kg/m2 vs. 25.0–29.9 kg/m2 vs. ≥ 30.0 kg/m2) and three age-related groups (20–30 years vs. 31–34 years vs. ≥ 35 years) which were compared for ART outcomes. Further, observations were divided into quartiles based on either of three parameters related to embryo outcome, i.e. (i) embryos developing between days 3 and 5 (ED3-5) and (ii) expanded blastocysts on day 5 (EB5), both expressed proportionally to the number of oocytes with two pronuclei (2PN), as well as (iii) the embryo utilization rate (EUR). Proportions of FF FA were then compared between Q1 and Q4, representing the quartile with the worst vs. the best embryo outcome, respectively. Finally, regression models were created to assess the relationships between BMI, age, FF total FA (TFA) concentration, relative proportions of specific FA and embryo outcome. Results Patients of Q1 had higher proportions of FF C20:5n-3, C22:6n-3 and total n-3 PUFA than Q4 patients. Furthermore, Q4 patients tended to be younger than Q1 patients. Within the whole cohort, the proportion of C20:5n-3 negatively correlated with ED3-5/2PN and EUR, while EB5/2PN tended to be negatively correlated with age. Regression models within the overweight and obese group confirmed the negative relation between C20:5n-3 and ED3-5/2PN, but also indicated additional associations: C18:1n-9 and C20:4n-6 were positively associated with ED3-5/2PN and EUR, respectively while the proportion of C18:0 was negatively associated with EUR. Conclusion The proportions of n-3 PUFA, particularly C20:5n-3 and C22:6n-3 were reduced in the patients’ quartile with the best embryo outcome. This group of patients was also younger. However, the embryo quality parameters of overweight/obese patients were not associated with age but were positively associated with FF C18:1n-9 and negatively with the proportions of C18:0 or C20:5n-3. Trial registration This study’ registration number was B670201627735.

Background It has been hypothesised that greater maternal adiposity before or during pregnancy causes greater offspring adiposity in childhood and adulthood, via causal intrauterine or periconceptional mechanisms. Previous Mendelian randomization (MR) estimates were imprecise, with wide confidence intervals that included potentially important protective or adverse effects, and may have been biased by collider effects or imperfect adjustment for genetic inheritance. Here we use an improved MR approach to investigate whether associations between maternal pre-/early pregnancy body mass index (BMI) and offspring adiposity from birth to adolescence are causal, or are instead due to confounding. Methods and findings We undertook confounder adjusted multivariable (MV) regression and Mendelian randomization (MR) using mother-offspring pairs from two UK cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) and Born in Bradford (BiB). In ALSPAC and BiB the outcomes were birthweight (BW; N = 9339) and BMI at age 1 (N = 8659) and 4 years (N = 7575), and in ALSPAC only we investigated BMI at 10 (N = 4476) and 15 years (N = 4112) and dual-energy X-ray absorptiometry (DXA) determined fat mass index (FMI) from age 10– 18 years (N = 2659 to 3855). We compared MR results from several polygenic risk scores (PRS), calculated from maternal non-transmitted alleles at between 29 and 80,939 single nucleotide polymorphisms (SNPs). MV and MR showed a consistent positive association of maternal BMI with BW, but for adiposity at most older ages MR estimates were weaker than MV estimates. In MV regression a one standard deviation (SD) higher maternal BMI was associated with a 0.13 (95% confidence interval [CI]: 0.10, 0.16) SD increase in offspring BW. The corresponding MR estimate from the strongest PRS (including up to 80,939 SNPs) was 0.14 (95% CI: 0.05, 0.23), with no difference between the two estimates (Pdifference = 0.84). For 15 year BMI the MV and MR estimates (80,939 SNPs) were 0.32 (95% CI: 0.29, 0.36) and 0.13 (95% CI: 0.01, 0.24) respectively (Pdifference = 1.0e-3). Results for FMI were similar to those for adolescent BMI. As the number of SNPs included in the PRS increased, the MR confidence intervals narrowed and the effect estimates for adolescent adiposity became closer to the MV estimates. Sensitivity analyses suggested the stronger effects with more SNPs were explained by horizontal pleiotropic bias away from zero. Consequently, the unbiased difference between the MV and MR estimates is probably greater than shown in our main analyses. Furthermore, MR estimates from IVs with fewer SNPs provided no strong evidence for a causal effect on adolescent adiposity. Conclusions Our results suggest that higher maternal pre-/early-pregnancy BMI is not a key driver of higher adiposity in the next generation. Thus, they support interventions that target the whole population for reducing overweight and obesity, rather than a specific focus on women of reproductive age.

INTRODUCTION Shoulder dystocia has remained an unpredictable and feared emergency in obstetrics. Some risk factors have been identified but nevertheless there is a lack of risk evaluation tools in clinical practice. The aim of this study was to evaluate the incidence and risk factors of shoulder dystocia in the Finnish population and to develop a shoulder dystocia risk score tool. MATERIAL AND METHODS This retrospective, population-based study included all deliveries in Finland between 2004 and 2017 (n = 800 484). The annual numbers of shoulder dystocia diagnoses were gathered from nationwide Finnish Medical Birth Register and Hospital Discharge Register. The incidence of shoulder dystocia was calculated in subgroups according to the mode of delivery, maternal diabetes status, body mass index (BMI), age, parity and gestational age. Based on these numbers, a shoulder dystocia risk score tool was created. RESULTS The overall incidence of shoulder dystocia was 0.18%. It increased significantly during the study period from 0.10% to 0.32% (P

Background/objective Children BMI is a longitudinal phenotype, developing through interplays between genetic and environmental factors. Whilst childhood obesity is escalating, we require a better understanding of its early origins and variation across generations to prevent it. Subjects/methods We designed a cross-cohort study including 12,040 Finnish children from the Northern Finland Birth Cohorts 1966 and 1986 (NFBC1966 and NFBC1986) born before or at the start of the obesity epidemic. We used group-based trajectory modelling to identify BMI trajectories from 2 to 20 years. We subsequently tested their associations with early determinants (mother and child) and the possible difference between generations, adjusted for relevant biological and socioeconomic confounders. Results We identified four BMI trajectories, 'stable-low' (34.8%), 'normal' (44.0%), 'stable-high' (17.5%) and 'early-increase' (3.7%). The 'early-increase' trajectory represented the highest risk for obesity. We analysed a dose-response association of maternal pre-pregnancy BMI and smoking with BMI trajectories. The directions of effect were consistent across generations and the effect sizes tended to increase from earlier generation to later. Respectively for NFBC1966 and NFBC1986, the adjusted risk ratios of being in the early-increase group were 1.08 (1.06-1.10) and 1.12 (1.09-1.15) per unit of pre-pregnancy BMI and 1.44 (1.05-1.96) and 1.48 (1.17-1.87) in offspring of smoking mothers compared to non-smokers. We observed similar relations with infant factors including birthweight for gestational age and peak weight velocity. In contrast, the age at adiposity peak in infancy was associated with the BMI trajectories in NFBC1966 but did not replicate in NFBC1986. Conclusions Exposures to adverse maternal predictors were associated with a higher risk obesity trajectory and were consistent across generations. However, we found a discordant association for the timing of adiposity peak over a 20-year period. This suggests the role of residual environmental factors, such as nutrition, and warrants additional research to understand the underlying gene-environment interplay.

Background Obesity susceptibility genes are highly expressed in the brain suggesting that they might exert their influence on body weight through eating-related behaviors. Objectives To examine whether the genetic susceptibility to obesity is mediated by eating behavior patterns. Methods Participants were 3977 twins (33% monozygotic, 56% females), aged 31–37 y, from wave 5 of the FinnTwin16 study. They self-reported their height and weight, eating behaviors (15 items), diet quality, and self-measured their waist circumference (WC). For 1055 twins with genome-wide data, we constructed a polygenic risk score for BMI (PRSBMI) using almost 1 million single nucleotide polymorphisms. We used principal component analyses to identify eating behavior patterns, twin modeling to decompose correlations into genetic and environmental components, and structural equation modeling to test mediation models between the PRSBMI, eating behavior patterns, and obesity measures. Results We identified 4 moderately heritable (h2 = 36–48%) eating behavior patterns labeled “snacking,” “infrequent and unhealthy eating,” “avoidant eating,” and “emotional and external eating.” The highest phenotypic correlation with obesity measures was found for the snacking behavior pattern (r = 0.35 for BMI and r = 0.32 for WC; P < 0.001 for both), largely due to genetic factors in common (bivariate h2 > 70%). The snacking behavior pattern partially mediated the association between the PRSBMI and obesity measures (βindirect = 0.06; 95% CI: 0.02, 0.09; P = 0.002 for BMI; and βindirect = 0.05; 95% CI: 0.02, 0.08; P = 0.003 for WC). Conclusions Eating behavior patterns share a common genetic liability with obesity measures and are moderately heritable. Genetic susceptibility to obesity can be partly mediated by an eating pattern characterized by frequent snacking. Obesity prevention efforts might therefore benefit from focusing on eating behavior change, particularly in genetically susceptible individuals.

A comprehensive overview is presented of the nutritional issues faced by people who use drugs or are undergoing treatment for recovery. Chronic substance use affects a person’s nutritional status and body composition through decreased intake, nutrient absorption, and dysregulation of hormones that alter the mechanisms of satiety and food intake. Anthropometrics alone is not the best indicator of nutritional status, because this population has hidden deficiencies and disturbed metabolic parameters. Socioeconomic factors (eg, higher education, higher income, presence of a partner, living at home) positively affect nutritional status. Scarce available data on users undergoing treatment indicate improvement in anthropometric and metabolic parameters but with micronutrient intake remaining suboptimal. Weight gain is noted especially among women who use drugs and potentially increases their risk of relapse. Finally, specific amino acids and omega-3 fatty acids are promising in decreasing relapse and improving mental health during treatment; however, additional high-quality studies are needed. Nutrition intervention for people who use drugs or are undergoing treatment for recovery is underused; comprehensive programs addressing this population’s unique needs are necessary. Future research will identify which components are needed.

INTRODUCTION: Regional outcomes after implantation of continuous-flow left ventricular assist devices (LVADs) have not been described. We examined differences in patient selection, survival, and adverse events across 3 geographic regions of the world: the Americas, Asia-Pacific, and Europe. METHODS: Using data from The International Society for Heart and Lung Transplantation Mechanically Assisted Circulatory Support registry, all adult patients implanted with a continuous-flow LVADs were included in this International Society for Heart and Lung Transplantation Mechanically Assisted Circulatory Support analysis (n = 15,560), of whom, 9,988 (64%) received axial-flow devices and 5,572 (36%) received centrifugal-flow devices. RESULTS: There were significant interregional differences in the rate of implantation of patients aged >70 years (Americas: 14%, Asia-Pacific: 1%, Europe: 5%; p < 0.0001), morbidly obese (Americas: 5%, Asia-Pacific: 1%, Europe: 1%; p < 0.0001), male (Americas: 79%, Asia-Pacific: 77%, Europe: 85%; p < 0.0001), and implanted as destination therapy (Americas: 48%, Asia-Pacific: 4%, Europe: 22%; p < 0.0001). The rates of centrifugal pump usage varied by region (Americas: 30%, Asia-Pacific: 34%, Eu: 74%; p < 0.0001). Survival rates varied by region and the type of pump flow, with survival at 12 and 48 months (axial flow vs centrifugal flow) being 82% vs 82% and 52% vs 53 in Americas; 92% vs 86% and 83% vs 74% in Asia-Pacific; and 80% vs 75% and 69% vs 53% in Europe, respectively (regional survival p < 0.0001). CONCLUSION: There are marked global differences in LVAD recipient characteristics, device utilization, and post-operative care. These heterogeneities along with differences in patient management and transplantation rates may impact long-term survival. Regional differences in adverse event incidence warrant further investigation. ispartof: JOURNAL OF HEART AND LUNG TRANSPLANTATION vol:39 issue:9 pages:904-914 ispartof: location:United States status: published

Cardiometabolic risk factors may be of key importance in the development of future brain diseases like dementia or depression. However, it remains unclear how these risk factors exactly affect the brain. Advanced MR imaging methods such as, diffusion weighted and functional MRI, can provide detailed insights into subtle brain changes, and potentially into early development of disease. In this narrative review, we summarize the available evidence on the associations of cardiometabolic risk factors with subtle changes in brain MRI measures. We found clear evidence that hyperglycemia, physical inactivity, central obesity, and hypertension are associated with both structural and functional brain alterations, while the role of dyslipidemia is far less clear. However, longitudinal evidence that assesses temporality of the associations with more advanced and thus more precise brain imaging methods is needed to improve our insights into the complex etiology of brain diseases.

Diet has important effects on normal physiology and the potential deleterious effects of high fat diets and obesity on male reproductive health are being increasingly described. We conducted a histological review of the effects of chronic high fat (HF) diet (using a mouse model fed a 45% fat diet for 21 weeks) with a discovery proteomic study to assess for changes in the abundance of proteins in the testis. Mice on a HF diet became obese and developed glucose intolerance. Using mass spectrometry, we identify 102 proteins affected in the testis of obese mice. These included structural proteins important for the blood testis barrier (filamin A, FLNA), proteins involved in oxidative stress responses (spermatogenesis associated 20, SPATA-20) and lipid homoeostasis (sterol regulatory element-binding protein 2, SREBP2 and apolipoprotein A1, APOA1). In addition, an important regulator protein paraspeckle component 1, PSPC-1, which interacts with the androgen receptor was significantly downregulated. Proteomic data was validated using both Western blotting and immunostaining which confirmed and localised protein expression in both mouse and human testis using biopsy specimens. This study focused mainly on the abnormalities that occurred at the protein level and as a result, we have identified several candidate proteins and conducted pathway analysis around the effects of HF diet on the testis providing novel insights not previously described. Some of the identified targets could be targeted therapeutically and future work is directed in this area.

Background Risankizumab is a humanized IgG monoclonal antibody that selectively inhibits interleukin-23 through binding the p19 subunit. In Phase 3 trials, risankizumab demonstrated superior efficacy compared with adalimumab and ustekinumab in patients with moderate-to-severe plaque psoriasis. Here, we evaluated the impact of baseline characteristics on efficacy of risankizumab compared with ustekinumab in patients with moderate-to-severe plaque psoriasis. Methods This analysis included all patients initially randomized to risankizumab or ustekinumab from the replicate, double-blinded, randomized, placebo-controlled phase 3 trials, UltIMMa-1 (NCT02684370) and UltIMMa-2 (NCT02684357). Patients received either risankizumab (150 mg) or ustekinumab (weight-based; 45 or 90 mg per label) at weeks 0, 4, 16, 28 and 40. Efficacy was assessed as the proportion of patients achieving >= 90% improvement in Psoriasis Area and Severity Index (PASI 90) at weeks 16 and 52 by baseline patient demographics, disease characteristics and prior biologic exposure. Mean per cent improvement in PASI was calculated by body weight and body mass index at week 52. Missing efficacy data were imputed as non-responders for categorical variables and last observation carried forward for continuous variables. Logistic regression analyses assessed for interactions between treatment and five independent variables (age, sex, weight, baseline PASI score and presence of psoriatic arthritis) at both weeks 16 and 52. Results Baseline patient demographics, disease characteristics and prior biologic exposure were similar between patients randomized to risankizumab (n = 598) and ustekinumab (n = 199). At weeks 16 and 52, risankizumab demonstrated superior efficacy compared with ustekinumab across these patient characteristics (P < 0.01). Logistic regression analyses demonstrated that risankizumab was superior to ustekinumab at weeks 16 and 52 in all models tested (P < 0.0001 for all). Conclusions Risankizumab demonstrated consistent and superior efficacy compared with ustekinumab regardless of patient demographics, disease characteristics or prior biologic exposure.

International audience; Background.We aimed to describe the immunosuppressive regimens and graft rejection rates in living-related HLA-identical (LR HLAid) renal transplantation.Methods.We performed a retrospective multicenter analysis of the French national database for LR HLAid renal transplantations performed between 2002 and 2012. Univariate and multivariate analysis were performed to determine risk factors for graft rejection in LR HLAid recipients.Results.A total of 27 218 renal transplantations were performed, of whom 163 had a LR HLAid donor. About immunosuppressive treatment

ObjectivesThis review examines how response rates to progestin treatment of low-grade endometrial cancer can be improved. In addition to providing a brief overview of the pathogenesis of low-grade endometrial cancer, we discuss limitations in the current classification of endometrial cancer and how stratification may be refined using molecular markers to reproducibly identify ‘low-risk’ cancers which may represent the best candidates for progestin therapy. We also discuss constraints in current approaches to progestin treatment of low-grade endometrial cancer and perform a systematic review of predictive biomarkers.MethodsPubMed, ClinicalTrials.gov, and Cochrane Library were searched for studies reporting pre-treatment biomarkers associated with outcome in women with low-grade endometrial cancer or endometrial hyperplasia with an intact uterus who received progestin treatment. Studies of fewer than 50 women were excluded. The study protocol was registered in PROSPERO (ID 152374). A descriptive synthesis of pre-treatment predictive biomarkers reported in the included studies was conducted.ResultsOf 1908 records reviewed, 19 studies were included. Clinical features such as age or body mass index cannot predict progestin response. Lesions defined as ‘low-risk’ by FIGO criteria (stage 1A, grade 1) can respond well; however, the reproducibility and prognostic ability of the current histopathological classification system is suboptimal. Molecular markers can be reproducibly assessed, have been validated as prognostic biomarkers, and may inform patient selection for progestin treatment. DNA polymerase epsilon (POLE)-ultramutated tumors and a subset of p53 wild-type or DNA mismatch repair (MMR)-deficient tumors with ‘low-risk’ features (eg, progesterone and estrogen receptor-positive) may have improved response rates, though this needs to be validated.DiscussionMolecular markers can identify cases which may be candidates for progestin treatment. More work is needed to validate these biomarkers and potentially identify new ones. Predictive biomarkers are anticipated to inform future research into progestin treatment of low-grade endometrial cancer and ultimately improve patient outcomes.

Background & aims: Prognostic significance of metabolically healthy overweight and obesity (MHO) is under debate. However the relationship between MHO and health-related quality of life (HRQoL) is less studied. We compared successful aging (longevity plus HRQoL) in men with MHO, metabolically healthy normal weight (MHN) and metabolically unhealthy overweight and obesity (MUO). Methods: In the Helsinki Businessmen Study longitudinal cohort, consisting of men born 1919 to 1934. In 1985/86, overweight (BMI >= 25 kg/m(2)) and metabolic health were determined in 1309 men (median age 60 years). HRQoL was assessed using RAND-36/SF-36 in 2000 and 2007, and all-cause mortality retrieved from registers up to 2018. The proportion of men reaching 90 years was also calculated. Results: Of the men, 469 (35.8%), 538 (41.1%), 276 (21.1%), and 26 (2.0%) were MHN, MHO, MUO and MUN, respectively. During the 32-year follow-up, 72.3% men died. With MHN as reference, adjusted hazard ratio with all-cause mortality was 1.08 (95% confidence interval [CI] 0.93 to 1.27) for MHO, and 1.18 (95% CI 0.95 to 1.47) for MUO. During follow-up, 273 men reached 90 years. With MHN as reference, adjusted odds ratio for MHO was 0.82 (95% CI 0.59 to 1.14) and 0.62 (95% CI 0.41 to 0.95) for MUO. Men in MHN group scored generally highest in RAND-36 HRQoL subscales in 2000 and 2007, of those significantly better in Physical functioning, Role physical, Role emotional, Bodily Pain, and General health sub-scales compared to MHO group in 2000. Conclusions: As compared to MHN, MHO in late midlife does not increase mortality, but impairs odds for successful aging. (C) 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The use of circulating biomarkers for heart failure (HF) is engrained in contemporary cardiovascular practice and provides objective information about various pathophysiological pathways associated with HF syndrome. However, biomarker profiles differ considerably among women and men. For instance, in the general population, markers of cardiac stretch (natriuretic peptides) and fibrosis (galectin‐3) are higher in women, whereas markers of cardiac injury (cardiac troponins) and inflammation (sST2) are higher in men. Such differences may reflect sex‐specific pathogenic processes associated with HF risk, but may also arise as a result of differences in sex hormone profiles and fat distribution. From a clinical perspective, sex‐related differences in biomarker levels may affect the objectivity of biomarkers in HF management because what is considered to be ‘normal’ in one sex may not be so in the other. The objectives of this review are, therefore: (i) to examine the sex‐specific dynamics of clinically relevant HF biomarkers in the general population, as well as in HF patients; (ii) to discuss the overlap between sex‐related and obesity‐related effects, and (iii) to identify knowledge gaps to stimulate research on sex‐related differences in HF.

Despite several pharmacological options, the clinical outcomes of major depressive disorder (MDD) are often unsatisfactory. Personalized psychiatry attempts to tailor therapeutic interventions according to each patient’s unique profile and characteristics. This approach can be a crucial strategy in improving pharmacological outcomes in MDD and overcoming trial-and-error treatment choices. In this narrative review, we evaluate whether sociodemographic (i.e., gender, age, race/ethnicity, and socioeconomic status) and clinical [i.e., body mass index (BMI), severity of depressive symptoms, and symptom profiles] variables that are easily assessable in clinical practice may help clinicians to optimize the selection of antidepressant treatment for each patient with MDD at the early stages of the disorder. We found that several variables were associated with poorer outcomes for all antidepressants. However, only preliminary associations were found between some clinical variables (i.e., BMI, anhedonia, and MDD with melancholic/atypical features) and possible benefits with some specific antidepressants. Finally, in clinical practice, the assessment of sociodemographic and clinical variables considered in our review can be valuable for early identification of depressed individuals at high risk for poor responses to antidepressants, but there are not enough data on which to ground any reliable selection of specific antidepressant class or compounds. Recent advances in computational resources, such as machine learning techniques, which are able to integrate multiple potential predictors, such as individual/ clinical variables, biomarkers, and genetic factors, may offer future reliable tools to guide personalized antidepressant choice for each patient with MDD.

General purpose To review the nutrition-related recommendations presented in the 2019 European Pressure Ulcer Advisory Panel, National Pressure Injury Advisory Panel, and Pan Pacific Pressure Injury Alliance Prevention and Treatment of Pressure Ulcers/Injuries: Clinical Practice Guideline with further discussion of nutrition for pressure injury management in the context of the recommendations. Target audience This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. Learning objectives/outcomes After participating in this educational activity, the participant should be better able to:1. Distinguish nutrition and malnutrition, especially as they relate to the development and healing of pressure injuries.2. Differentiate the tools and techniques that help clinicians assess nutrition status as well as the causes of pressure injuries in specific populations.3. Identify interventions for improving nutrition status and promoting pressure injury healing. Abstract Macro- and micronutrients are required by each organ system in specific amounts to promote the growth, development, maintenance, and repair of body tissues. Specifically, nutrition plays an important role in the prevention and treatment of pressure injuries. The purpose of this manuscript is to review the nutrition-related recommendations presented in the 2019 European Pressure Ulcer Advisory Panel, National Pressure Injury Advisory Panel, and Pan Pacific Pressure Injury Alliance Prevention and Treatment of Pressure Ulcers/Injuries: Clinical Practice Guideline. Nutrition for pressure injury management is discussed in the context of the recommendations.

Background Carpal tunnel release is one of the most common procedures in hand surgery. There is only scarce evidence regarding whether platelet inhibitors increase the risk of developing postoperative hemorrhage in carpal tunnel release. Methods This is a multicenter, propensity score-matched study including 635 carpal tunnel releases in 497 patients. Multivariate regression models were adjusted with the propensity score, which was developed to mitigate differences in patients with and without platelet inhibition with acetylsalicylic acid. Propensity score matching provides results close to the statistical quality of randomized controlled trials. The primary study endpoint was postoperative bleeding complication, defined as acute bleeding leading to reoperation or hematoma leading to physician visit. Patient satisfaction, functional outcome measured with the Boston Carpal Tunnel Questionnaire, and onset of surgical-site infection were also analyzed. Results Bleeding complications were observed in 56 procedures (8.8 percent). After propensity score matching, there was no significant difference between the patients with and without acetylsalicylic acid treatment (p = 0.997). History of thyroid disease (p = 0.035) and of rheumatoid arthritis (p = 0.026) were independent risk factors, whereas higher body mass index might have a beneficial effect (p = 0.006). Patients with postoperative bleeding had significantly impaired functional outcome as measured with the Boston Carpal Tunnel Questionnaire (p = 0.026). Median satisfaction in the investigated study population was 10 of 10 points and did not differ significantly between the antiplatelet and the non-antiplatelet cohorts (p = 0.072) CONCLUSION:: Carpal tunnel release under platelet inhibition with acetylsalicylic acid is safe and can be performed without interruption of such medication. Clinical question/level of evidence Therapeutic, III.

Heterogeneity of interindividual and intraindividual responses to interventions is often observed in randomized, controlled trials for obesity. To address the global epidemic of obesity and move toward more personalized treatment regimens, the global research community must come together to identify factors that may drive these heterogeneous responses to interventions. This project, called OBEDIS (OBEsity Diverse Interventions Sharing - focusing on dietary and other interventions), provides a set of European guidelines for a minimal set of variables to include in future clinical trials on obesity, regardless of the specific endpoints. Broad adoption of these guidelines will enable researchers to harmonize and merge data from multiple intervention studies, allowing stratification of patients according to precise phenotyping criteria which are measured using standardized methods. In this way, studies across Europe may be pooled for better prediction of individuals' responses to an intervention for obesity - ultimately leading to better patient care and improved obesity outcomes. © 2020 The Author(s) Published by S. Karger AG, Basel.

Childhood obesity/overweight is a worldwide concern and its prevalence is increasing in many countries. The first aim of this study is to analyse the trends in overweight and obesity among children under the age of five in Turkey based on the new World Health Organization (WHO) standards, using data from the ‘five-round of the Turkey Demographic and Health Surveys’ (TDHSs). The second aim is to examine whether or not the maternal/household and individual-level factors are associated with overweight/obesity using TDHS 2003, 2008, and 2013 datasets. A total sample of 14,231 children under the age of five were extracted from the TDHS in 1993, 1998, 2003, 2008, and 2013 to determine the prevalence of the trend. Pooled data from 8,812 children were included in the analysis to examine factors associated with overweight/obesity. Taking into account the clustered data structure, multilevel logistic regression models were utilised. In 1993, 1998, 2003, 2008, and 2013 the prevalence of overweight children was 5.3%, 4.9%, 10.0%, 11% and 11.6%, respectively. The factors that were independently associated with overweight/obesity were as follows: living in single-parent households (adjusted odds ratio (aOR) = 2.27, 95%CI = 1.21–4.26), compared to living in dual-parent households; having an obese mother (aOR = 4.25, 95%CI = 1.73–10.44), overweight mother (aOR = 3.15, 95%CI = 1.29–7.69), and a normal-weight mother (aOR = 2.70, 95%CI = 1.11–6.59) compared to having an underweight mother; being aged between 13–24 months (aOR = 1.72, 95%CI = 1.30 to 2.27), compared to being aged 0-12 months; male gender (aOR = 1.30, 95%CI = 1.11 to 1.53); being stunted (aOR = 2.18, 95%CI = 1.74 to 2.73); high birth weight (aOR = 1.55, 95%CI = 1.08 to 2.23) compared to low birth weight. In addition, overweight was higher in children of mothers who had completed primary school (aOR = 1.21, 95%CI = 1.01 to 1.59) than children of mothers who had not completed primary school. These findings reveal that, over the years, there has been a substantial increase in obesity/overweight among children which demonstrates the importance of evaluating the overweight indicators at the maternal/household level.

IntroductionBehavioural interventions in early life appear to show some effect in reducing childhood overweight and obesity. However, uncertainty remains regarding their overall effectiveness, and whether effectiveness differs among key subgroups. These evidence gaps have prompted an increase in very early childhood obesity prevention trials worldwide. Combining the individual participant data (IPD) from these trials will enhance statistical power to determine overall effectiveness and enable examination of intervention-covariate interactions. We present a protocol for a systematic review with IPD meta-analysis to evaluate the effectiveness of obesity prevention interventions commencing antenatally or in the first year after birth, and to explore whether there are differential effects among key subgroups.Methods and analysisSystematic searches of Medline, Embase, CENTRAL, CINAHL, PsycInfo, and trial registries for all ongoing and completed randomised controlled trials evaluating behavioural interventions for the prevention of early childhood obesity have been completed up to March 2020 and will be updated annually to include additional trials. Eligible trialists will be asked to share their IPD; if unavailable, aggregate data will be used where possible. An IPD meta-analysis and a nested prospective meta-analysis (PMA) will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome will be body mass index (BMI) z-score at age 24 +/- 6 months using World Health Organisation Growth Standards, and effect differences will be explored among pre-specified individual and trial-level subgroups. Secondary outcomes include other child weight-related measures, infant feeding, dietary intake, physical activity, sedentary behaviours, sleep, parenting measures and adverse events.Ethics and disseminationApproved by The University of Sydney Human Research Ethics Committee (2020/273) and Flinders University Social and Behavioural Research Ethics Committee (project no. HREC CIA2133-1). Results will be relevant to clinicians, child health services, researchers, policy-makers and families, and will be disseminated via publications, presentations, and media releases.RegistrationProspectively registered on PROSPERO: CRD42020177408STRENGTHS AND LIMITATIONS OF THIS STUDYThis will be the largest individual participant data (IPD) meta-analysis evaluating behavioural interventions for the prevention of early childhood obesity to date, and will provide the most reliable and precise estimates of early intervention effects to inform future decision-making.IPD meta-analysis methodology will enable unprecedented exploration of important individual and trial-level characteristics that may be associated with childhood obesity or that may be effect modifiers.The proposed innovative methodologies are feasible and have been successfully piloted by members of our group.It may not be possible to obtain IPD from all eligible trials; in this instance, aggregate data will be used where available, and sensitivity analyses will be conducted to assess inclusion bias.Outcome measures may be collected and reported differently across included trials, potentially increasing imprecision; however, we will harmonise available data where possible, and encourage those planning or conducting ongoing trials to collect common core outcomes following prospective meta-analysis methodology.

BackgroundInpatient pediatric obesity treatments are highly effective, although dropouts and weight regain threaten long-term results. Preliminary data indicate that leptin, adiponectin, and cardiometabolic comorbidities might predict treatment outcomes. Previous studies have mainly focused on the individual role of adipokines and comorbidities, which is counterintuitive, as these risk factors tend to cluster. This study aimed to predict the dropouts and treatment outcomes by pre-treatment patient characteristics extended with cardiometabolic comorbidities (individually and in total), leptin, and adiponectin.MethodsChildren aged 8–18 years were assessed before, immediately after and 6 months after a 12-month inpatient obesity treatment. Anthropometric data were collected at each visit. Pre-treatment lipid profiles; glucose, insulin, leptin, and adiponectin levels; and blood pressure were measured. The treatment outcome was evaluated by the change in body mass index (BMI) standard deviation score (SDS) corrected for age and sex.ResultsWe recruited 144 children with a mean age of 14.3 ± 2.2 years and a mean BMI of 36.7 ± 6.2 kg/m2 corresponding to 2.7 ± 0.4 BMI SDS. The 57 patients who dropped out during treatment and the 44 patients who dropped out during aftercare had a higher pre-treatment BMI compared to the patients who completed the treatment (mean BMI, 38.3 ± 6.8 kg/m2 vs 35.7 ± 5.5 kg/m2) and those who completed aftercare (mean BMI, 34.6 ± 5.3 kg/m2 vs 37.7 ± 6.3 kg/m2) (all pPatients lost on average 1.0 ± 0.4 SDS during treatment and regained 0.4 ± 0.3 SDS post-treatment corresponding to regain of 43 ± 27% (calculated as the increase in BMI SDS post-treatment over the BMI SDS lost during treatment). A higher BMI and more comorbidities inversely predicted BMI SDS reduction in linear regression (all pThe absolute BMI SDS increase after returning home was predicted by pre-treatment leptin and systolic blood pressure, whereas the post-treatment BMI SDS regain was predicted by pre-treatment age, leptin, and adiponectin levels (all pConclusionPatients who need treatment the most are at increased risk for dropouts and weight regain, emphasizing the urgent need for interventions to reduce dropout and support inpatients after discharge. Furthermore, this study is the first to report that pre-treatment leptin and adiponectin levels predict post-treatment BMI SDS regain, requiring further research.

ObjectiveTo evaluate the association between overweight and obesity on the clinical course and outcomes in patients hospitalized with COVID-19.DesignRetrospective, observational cohort study.MethodsWe performed a multicenter, retrospective, observational cohort study of hospitalized COVID-19 patients to evaluate the associations between overweight and obesity on the clinical course and outcomes.ResultsOut of 1634 hospitalized COVID-19 patients, 473 (28.9%) had normal weight, 669 (40.9%) were overweight, and 492 (30.1%) were obese. Patients who were overweight or had obesity were younger, and there were more women in the obese group. Normal-weight patients more often had pre-existing conditions such as malignancy, or were organ recipients. During admission, patients who were overweight or had obesity had an increased probability of acute respiratory distress syndrome [OR 1.70 (1.26-2.30) and 1.40 (1.01-1.96)], respectively and acute kidney failure [OR 2.29 (1.28-3.76) and 1.92 (1.06-3.48)], respectively. Length of hospital stay was similar between groups. The overall in-hospital mortality rate was 27.7%, and multivariate logistic regression analyses showed that overweight and obesity were not associated with increased mortality compared to normal-weight patients.ConclusionIn this study, overweight and obesity were associated with acute respiratory distress syndrome and acute kidney injury, but not with in-hospital mortality nor length of hospital stay.

We evaluated the epidemiological evidence on the built environment and its link to childhood obesity, focusing on environmental factors such as traffic noise and air pollution, as well as physical factors potentially driving obesity-related behaviors, such as neighborhood walkability and availability and accessibility of parks and playgrounds. Eligible studies were (i) conducted on human children below the age of 18 years, (ii) focused on body size measurements in childhood, (iii) examined at least one built environment characteristic, (iv) reported effect sizes and associated confidence intervals, and (v) were published in English language. A z test, as alternative to the meta-analysis, was used to quantify associations due to heterogeneity in exposure and outcome definition. We found strong evidence for an association of traffic-related air pollution (nitrogen dioxide and nitrogen oxides exposure, p

BackgroundAsthma is a common respiratory disease in children. We aimed to update information about the incidence and mortality and disability-adjusted life years (DALYs) of childhood asthma and provide evidence-based recommendations for childhood asthma prevention.MethodsData were obtained from the Global Burden of Disease (GBD) study, which was conducted from 1990 to 2019 in 204 countries. First, we estimated incidence, mortality and DALY rates of childhood asthma using a Bayesian meta-regression model. Second, we analyzed the relationship between the sociodemographic index (SDI) and DALYs in different age groups. Third, we studied changes in trends of the age-standardized DALY rate between 1990 and 2019 based on age group, SDI, and risk factors.ResultsGlobally, the number of deaths due to childhood asthma and the incidence and DALY rates were 12.9 thousand (95% UI 10.6 to 15.7), 22 million (95% UI 15 to 31), and 5.1 million (95% UI 3.4 to 7.5) in 2019, decreasing by 65.1% (95% UI 47.6 to 72.4), 5.3% (95% UI 2.6 to 8.8) and 30% (95% UI 18 to 41) from those in 1990, respectively. With the exception of high-SDI regions, the age-standardized DALY rate in all age groups in all SDI regions declined. In 2019, the age-standardized DALY rate in 1- to 4-year-old individuals was highest in low-SDI regions and that of 5- to 19-year-old individuals was highest in high-SDI regions. In contrast to low-SDI regions, individuals in high-SDI regions had a higher risk of DALYs due to asthma, except in those aged 1 to 4 years. A high body mass index (BMI) was a stronger risk factor than occupational asthmagens for childhood asthma.ConclusionOur findings provide insight into asthma prevention and treatment through the identification of key factors related to childhood asthma. Based on the data available, different risk factors according to age group and region/country suggest different prevention strategies, which is key for preventing childhood asthma.

We conducted a systematic review and meta-analysis of the associations between prenatal exposure to persistent organic pollutants (POPs) and childhood obesity. We focused on organochlorines (dichlorodiphenyltrichloroethane [DDT], dichlorodiphenyldichloroethylene [DDE], hexachlorobenzene [HCB], and polychlorinated biphenyls [PCBs]), perfluoroalkyl and polyfluoroalkyl substances (PFAS), and polybrominated diphenyl ethers (PBDEs) that are the POPs more widely studied in environmental birth cohorts so far. We search two databases (PubMed and Embase) through July/09/2021 and identified 33 studies reporting associations with prenatal organochlorine exposure, 21 studies reporting associations with prenatal PFAS, and five studies reporting associations with prenatal PBDEs. We conducted a qualitative review. Additionally, we performed random-effects meta-analyses of POP exposures, with data estimates from at least three prospective studies, and BMI-z. Prenatal DDE and HCB levels were associated with higher BMI z-score in childhood (beta: 0.12, 95% CI: 0.03, 0.21; I2 : 28.1% per study-specific log increase of DDE and beta: 0.31, 95% CI: 0.09, 0.53; I2 : 31.9% per study-specific log increase of HCB). No significant associations between PCB-153, PFOA, PFOS, or pentaPBDEs with childhood BMI were found in meta-analyses. In individual studies, there was inconclusive evidence that POP levels were positively associated with other obesity indicators (e.g., waist circumference). This study is an ancillary endeavor of the Science & Technology in childhood Obesity Policy (STOP) project (H2020 SC2; ref. 774548). This study was supported by the National Institute of Environmental Health Science (NIEHS, R01ES030364). Additional funding from NIEHS includes R21ES029681 (Chatzi, McConnell, Conti, Valvi, Stratakis), R01ES029944 (Chatzi, Conti, Valvi, Rock), R01ES030691 (Chatzi, McConnell, Conti, Valvi), R21ES028903 (Chatzi, McConnell, Valvi), P30ES007048 (McConnell, Chatzi, Conti, Stratakis), R21ES029328 (Valvi), and P30ES023515 (Valvi). Additional funding from NIH supported Dr. Conti (P01CA196569, R01CA140561, R01ES016813), and Dr. Stratakis (P30DK048522). Dr La Merill received additional funding from USDA National Institute of Food and Agriculture, Hatch project: 1002182.

Background: Modifiable vascular risk factors have been associated with late-life cognitive impairment. The Life Simple 7 (LS7) score comprises seven cardiovascular health metrics: smoking, diet, physical activity, body mass index, plasma glucose, total serum cholesterol, and blood pressure. Objective: To investigate the association between individual and composite LS7 metrics and rate of cognitive decline, and potential differences in these associations between young-old and old-old individuals. Methods: This cohort study included 1,950 participants aged≥60 years (M = 70.7 years) from the Swedish National Study on Aging and Care-Kungsholmen (SNAC-K), who underwent repeated neuropsychological testing (episodic and semantic memory, verbal fluency, processing speed, global cognition) across 12 years. The LS7 score was assessed at baseline and categorized as poor, intermediate, or optimal. Level and change in cognitive performance as a function of LS7 categories were estimated using linear mixed-effects models. Results: Having an optimal LS7 total score was associated with better performance (expressed in standard deviation units) at baseline for perceptual speed (β= 0.21, 95%CI 0.12–0.29), verbal fluency (β= 0.08, 0.00–0.16), and global cognition (β= 0.06, 0.00–0.12) compared to the poor group. Age-stratified analyses revealed associations for cognitive level and change only in the young-old (

Aims/hypothesis Observational studies have found an increased risk of latent autoimmune diabetes in adults (LADA) associated with low birthweight and adult overweight/obese status. We aimed to investigate whether these associations are causal, using a two-sample Mendelian randomisation (MR) design. In addition, we compared results for LADA and type 2 diabetes. Methods We identified 43 SNPs acting through the fetal genome as instrumental variables (IVs) for own birthweight from a genome-wide association study (GWAS) of the Early Growth Genetics Consortium (EGG) and the UK Biobank. We identified 820 SNPs as IVs for adult BMI from a GWAS of the UK Biobank and the Genetic Investigation of ANthropometric Traits consortium (GIANT). Summary statistics for the associations between IVs and LADA were extracted from the only GWAS involving 2634 cases and 5947 population controls. We used the inverse-variance weighted (IVW) estimator as our primary analysis, supplemented by a series of sensitivity analyses. Results Genetically determined own birthweight was inversely associated with LADA (OR per SD [~500 g] decrease in birthweight 1.68 [95% CI 1.01, 2.82]). In contrast, genetically predicted BMI in adulthood was positively associated with LADA (OR per SD [~4.8 kg/m2] increase in BMI 1.40 [95% CI 1.14, 1.71]). Robust results were obtained in a range of sensitivity analyses using other MR estimators or excluding some IVs. With respect to type 2 diabetes, the association with birthweight was not stronger than in LADA while the association with adult BMI was stronger than in LADA. Conclusions/ interpretation This study provides genetic support for a causal link between low birthweight, adult overweight/obese status and LADA. Graphical abstract

The comet assay is widely used for quantification of genomic damage in humans. Peripheral blood derived mononuclear cells (PBMCs) are the most often used cell type for this purpose. Since the comet assay can be performed in an enhanced throughput format, it can be applied to large sample collections such as biobanks. The European Prospective Investigation into Cancer and Nutrition (EPIC) study is one of the largest existing prospective cohort studies, and the German Cancer Research Institute (DKFZ) in Heidelberg is a participating center with 25.000 frozen blood samples stored from around 25 years ago, enabling retrospective assessment of disease risk factors. However, experience with decades long frozen samples in the comet assay is so far missing. In Heidelberg, 800 study participants were re-invited twice between 2010 and 2012 to donate further blood samples. Here, we analyzed 299 Heidelberg-EPIC samples, compiled from frozen PBMC and buffy coat preparations selected from the different sampling time points. In addition, 47 frozen PBMC samples from morbidly obese individuals were included. For buffy coat samples, we observed a poor correlation between DNA damage in the same donors assessed at two sampling time points. Additionally, no correlation between DNA damage in buffy coat samples and PBMCs was found. For PBMCs, a good correlation was observed between samples of the same donors at the two time points. DNA damage was not affected by age and smoking status, but high BMI (>30; obesity) was associated with increased DNA damage in PBMCs. There was no indication for a threshold of a certain BMI for increased DNA damage. In conclusion, while 25 year-long stored buffy coat preparations may require adaptation of certain experimental parameters such as cell density and electrophoresis conditions, frozen PBMC biobank samples can be analyzed in the comet assay even after a decade of storage.

Background High rates of adverse pregnancy outcomes globally raise the need to understand risk factors and develop preventative interventions. The Pregnancy Outcomes in the Era of Universal Antiretroviral Treatment in Sub-Saharan Africa (POISE Study) was a prospective, observational cohort study conducted from 2016 to 2017 in Blantyre, Malawi. We examine the associations between indicators of nutritional status, specifically mid-thigh circumference (MTC) and body-mass index (BMI), and adverse pregnancy outcomes, low birth weight (LBW), preterm birth (PTB), and small-for-gestational age (SGA), in a cohort of HIV-infected and HIV-uninfected women. Methods Sociodemographic, clinical, laboratory, and maternal height, weight and MTC data were collected immediately before or after delivery at the Queen Elizabeth Central Hospital (QEHC) and 4 affiliated health centers in Blantyre, Malawi. LBW was defined as birth weight Results Data from 1298 women were analyzed: 614 HIV-infected and 684 HIV-uninfected. MTC was inversely associated with LBW (adjusted odds ratio [aOR] = 0.95, p = 0.03) and PTB (aOR 0.92, p p = 0.53). Similarly, higher BMI was significantly associated with lower odds of PTB (aOR 0.90, p p = 0.05), and SGA (aOR 0.95, p = 0.04). Conclusions We observed an inverse relationship between MTC and adverse pregnancy outcomes in Malawi irrespective of HIV infection. MTC performs comparably to BMI; the ease of measuring MTC could make it a practical tool in resource-constrained settings for identification of women at risk of adverse pregnancy outcomes.

Objectives: This study aims to evaluate the clinical, functional, and radiological features of hand osteoarthritis (OA) and to examine their relationships in different geographic samples of the Turkish population. Patients and methods: Between April 2017 and January 2019, a total of 520 patients (49 males, 471 females; mean age: 63.6±9.8 years) with hand OA were included in the study from 26 centers across Turkey by the Turkish League Against Rheumatism (TLAR). The demographic characteristics, grip strengths with Jamar dynamometer, duration of hand pain (month), the severity of hand pain (Visual Analog Scale [VAS]), and morning stiffness were evaluated. The functional disability was evaluated with Duruöz Hand Index (DHI). The Kellgren-Lawrence (KL) OA scoring system was used to assess the radiological stage of hand OA. Results: The DHI had significant correlations with VAS-pain (r=0.367, p0.05). The differences between the groups of radiological hand OA grades in terms of age (p=0.007), VAS-pain (p0.05 for all). Conclusion: In our population, the patients with hand OA had pain, functional disability, and weak grip strength. The functional impairment was significantly correlated with the severity of the pain, and the functional status was worse in high radiological hand OA grades.

The underlying cell types mediating predisposition to obesity remain largely obscure. Here, we integrated recently published single-cell RNA-sequencing (scRNA-seq) data from 727 peripheral and nervous system cell types spanning 17 mouse organs with body mass index (BMI) genome-wide association study (GWAS) data from >457,000 individuals. Developing a novel strategy for integrating scRNA-seq data with GWAS data, we identified 26, exclusively neuronal, cell types from the hypothalamus, subthalamus, midbrain, hippocampus, thalamus, cortex, pons, medulla, pallidum that were significantly enriched for BMI heritability (p−4). Using genes harboring coding mutations associated with obesity, we replicated midbrain cell types from the anterior pretectal nucleus and periaqueductal gray (p−4). Together, our results suggest that brain nuclei regulating integration of sensory stimuli, learning and memory are likely to play a key role in obesity and provide testable hypotheses for mechanistic follow-up studies.

Background This study aimed to estimate annual health care and lost productivity costs associated with excess weight among the adult population in Belgium, using national health data. Methods Health care costs and costs of absenteeism were estimated using data from the Belgian national health interview survey (BHIS) 2013 linked with individual health insurance data (2013–2017). Average yearly health care costs and costs of absenteeism were assessed by body mass index (BMI) categories – i.e., underweight (BMI 2), normal weight (18.5 ≤ BMI 2), overweight (25 ≤ BMI 2) and obesity (BMI ≥ 30 kg/m2). Health care costs were also analysed by type of cost (i.e. ambulatory, hospital, reimbursed medication). The cost attributable to excess weight and the contribution of various other chronic conditions to the incremental cost of excess weight were estimated using the method of recycled prediction (a.k.a. standardisation). Results According to BHIS 2013, 34.7% and 13.9% of the Belgian adult population were respectively affected by overweight or obesity. They were mostly concentrated in the age-group 35–65 years and had significantly more chronic conditions compared to the normal weight population. Average total healthcare expenses for people with overweight and obesity were significantly higher than those observed in the normal weight population. The adjusted incremental annual health care cost of excess weight in Belgium was estimated at €3,329,206,657 (€651 [95% CI: €144-€1,084] and €1,015 [95% CI: €343–€1,697] per capita for individuals with overweight and obesity respectively). The comorbidities identified to be the main drivers for these incremental health care costs were hypertension, high cholesterol, serious gloom and depression. Mean annual incremental cost of absenteeism for overweight accounted for €242 per capita but was not statistically significant, people with obesity showed a significantly higher cost (p Conclusions The mean annual incremental cost of excess weight in Belgium is of concern and stresses the need for policy actions aiming to reduce excess body weight. This study can be used as a baseline to evaluate the potential savings and health benefits of obesity prevention interventions.

Background: Stroke is the second leading cause of death worldwide with heterogeneous characteristics. The subtypes of stroke are due to different pathophysiological regulations and causes. This study aimed to investigate the correlation of serum levels of apolipoprotein B 48, interleukin-1 beta and Homocysteine with BMI in patients with ischemic stroke (IS). Methods: Over one hundred controls (120) and an equal number of IS patients, including 31 women and 89 men, were recruited to participate in the case-control study conducted at Imam Reza Hospital (Tabriz, Iran) from February 2019 to March 2020. We measured serum levels of apolipoprotein B 48, interleukin-1 beta, and Homocysteine. Receiver operating characteristic analysis (ROC) was performed to evaluate the diagnostic value of these indices in patients and control groups. Results: The mean serum levels of apolipoprotein B 48, interleukin-1 beta, and Homocysteine, were significantly increased in the experimental group compared to the control group with a p-value of 0.001. The ROC curve analysis showed that the area under the curve for apo B48, IL-1 beta, hs-CRP, and Homocysteine serum levels were 0.94, 0.98, 0.99, and 1, respectively. Conclusions: The results of our current study show that the determination of serum levels of apolipoprotein B 48, interleukin-1 beta, and Homocysteine can potentially be used to monitor and diagnose IS patients. However, there was no statistically significant correlation between serum levels of apolipoprotein B 48, interleukin 1 beta and Homocysteine and BMI in the patient group. However, there was a statistically significant inverse correlation between serum levels of high-sensitivity C-reactive protein (hs-CRP) and BMI in the patient group., Research Vice-Chancellor of Tabriz University of medical sciences, Tabriz, IRAN [25992], The present study was supported by grants from the Research Vice-Chancellor of Tabriz University of medical sciences, Tabriz, IRAN grant no. 25992.

(1) Background: The association between metabolic obesity phenotypes and incident lung cancer (LC) remains unclear. (2) Methods: Based on the combination of baseline BMI categories and metabolic health status, participants were categorized into eight groups: metabolically healthy underweight (MHUW), metabolically unhealthy underweight (MUUW), metabolically healthy normal (MHN), metabolically unhealthy normal (MUN), metabolically healthy overweight (MHOW), metabolically unhealthy overweight (MUOW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). The Cox proportional hazards model and Mendelian randomization (MR) were applied to assess the association between metabolic obesity phenotypes with LC risk. (3) Results: During a median follow-up of 9.1 years, 3654 incident LC patients were confirmed among 450,482 individuals. Compared with participants with MHN, those with MUUW had higher rates of incident LC (hazard ratio (HR) = 3.24, 95% confidence interval (CI) = 1.33–7.87, p = 0.009). MHO and MHOW individuals had a 24% and 18% lower risk of developing LC, respectively (MHO: HR = 0.76, 95% CI = 0.61–0.95, p = 0.02; MHO: HR = 0.82, 95% CI = 0.70–0.96, p = 0.02). No genetic association of metabolic obesity phenotypes and LC risk was observed in MR analysis. (4) Conclusions: In this prospective cohort study, individuals with MHOW and MHO phenotypes were at a lower risk and MUUW were at a higher risk of LC. However, MR failed to reveal any evidence that metabolic obesity phenotypes would be associated with a higher risk of LC.

Background Obesity and type 2 diabetes are well-known risk factors for heart failure (HF). Although obesity has increased in type 1 diabetes, studies regarding HF in this population are scarce. Therefore, we investigated the impact of body fat distribution on the risk of HF hospitalization or death in adults with type 1 diabetes at different stages of diabetic nephropathy (DN). Methods From 5401 adults with type 1 diabetes in the Finnish Diabetic Nephropathy Study, 4668 were included in this analysis. The outcome was HF hospitalization or death identified from the Finnish Care Register for Health Care or the Causes of Death Register until the end of 2017. DN was based on urinary albumin excretion rate. A body mass index (BMI) ≥ 30 kg/m2 defined general obesity, whilst WHtR ≥ 0.5 central obesity. Multivariable Cox regression was used to explore the associations between central obesity, general obesity and the outcome. Then, subgroup analyses were performed by DN stages. Z statistic was used for ranking the association. Results During a median follow-up of 16.4 (IQR 12.4–18.5) years, 323 incident cases occurred. From 308 hospitalizations due to HF, 35 resulted in death. Further 15 deaths occurred without previous hospitalization. The WHtR showed a stronger association with the outcome [HR 1.51, 95% CI (1.26–1.81), z = 4.40] than BMI [HR 1.05, 95% CI (1.01–1.08), z = 2.71]. HbA1c [HR 1.35, 95% CI (1.24–1.46), z = 7.19] was the most relevant modifiable risk factor for the outcome whereas WHtR was the third. Individuals with microalbuminuria but no central obesity had a similar risk of the outcome as those with normoalbuminuria. General obesity was associated with the outcome only at the macroalbuminuria stage. Conclusions Central obesity associates with an increased risk of heart failure hospitalization or death in adults with type 1 diabetes, and WHtR may be a clinically useful screening tool.