No abstract

Glycemic traits are used to diagnose and monitor type 2 diabetes, and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here, we aggregated genome-wide association studies in up to 281,416 individuals without diabetes (30% non-European ancestry) with fasting glucose, 2h-glucose post-challenge, glycated hemoglobin, and fasting insulin data. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P <5x10 -8 ), 80% with no significant evidence of between-ancestry heterogeneity. Analyses restricted to European ancestry individuals with equivalent sample size would have led to 24 fewer new loci. Compared to single-ancestry, equivalent sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase understanding of diabetes pathophysiology by use of trans-ancestry studies for improved power and resolution.

The LIFE Child study is a large population-based longitudinal childhood cohort study conducted in the city of Leipzig, Germany. As a part of LIFE, a research project conducted at the Leipzig Research Center for Civilization Diseases, it aims to monitor healthy child development from birth to adulthood and to understand the development of lifestyle diseases such as obesity. The study consists of three interrelated cohorts; the birth cohort, the health cohort, and the obesity cohort. Depending on age and cohort, the comprehensive study program comprises different medical, psychological, and sociodemographic assessments as well as the collection of biological samples. Optimal data acquisition, process management, and data analysis are guaranteed by a professional team of physicians, certified study assistants, quality managers, scientists and statisticians. Due to the high popularity of the study, more than 3000 children have already participated until the end of 2015, and two-thirds of them participate continuously. The large quantity of acquired data allows LIFE Child to gain profound knowledge on the development of children growing up in the twenty-first century. This article reports the number of available and analyzable data and demonstrates the high relevance and potential of the study.

Metabolic syndrome (MetS) is recognized as an escalating major health risk in adults as well as in children and adolescents. Its prevalence ranges from 6 to 39% depending on the applied definition criteria. To date, there is no consensus on a MetS definition for children and adolescents. However, most authors agree on essential components such as glucose intolerance, central obesity, hypertension, and dyslipidemia; each representing a risk for cardiovascular disease. Recently, associations between MetS and non-alcoholic fatty liver disease, hyperuricemia, and sleep disturbances have emerged. Biomarkers like adipocytokines are a subject of current research as they are implicated in the pathogenesis of the MetS. Epigenetics and gestational programming, especially the role of microRNA, comprise a novel, rapidly developing and promising research focus on the topic of MetS. MicroRNAs are increasingly valued for potential roles in the diagnosis, stratification, and therapeutics of MetS. Early detection of risk factors, screening for metabolic disturbances, and the identification of new therapies are major aims to reduce morbidity and mortality related to MetS. Dietary modification and physical activity are currently the only adopted treatment approaches. Pharmacological therapies and bariatric surgery are still contradictory and, therefore, are only recommended in selected high-risk cases.

Background: There is concern that pandemic measures put a strain on the health and well-being of children. We investigated the effects of the COVID-19 pandemic, the lockdown, and social distancing on the well-being, media use, and emotions of children and adolescents between 9 and 18 years. Methods:We used linear and proportional odds logistic regression correcting for age, sex, and socioeconomic status (SES) and to compare media use, peers/social support, physical, and psychological well-being between 2019 (pre-COVID baseline) and two time points shortly after the start of the lockdown (last week of March and April 2020, respectively) in 391 9-19-year-old healthy children and adolescents of the LIFE Child cohort. COVID-19-related feelings and their relationship to age, sex, and SES were assessed at two time points during lockdown. Results:We found significantly lower scores in physical and psychological wellbeing during lockdown compared to baseline. The effect was significantly stronger in children with medium/low SES. Perceived social support scores were also significantly lower during the lockdown. The percentage of children who had no contact with their peers (in-person or online) increased from 3% pre-COVID to 14% and 13% in April and March 2020, respectively. About 80% of the children missed in-person contacts with friends. Most of the children worried more about the health of their families than their own. Sixty percent worried about the international situation at least moderately, whereas only 20% were afraid of COVID-19 itself. The percentage of children who believed it would never be as before COVID-19 rose from 7.4% at the beginning lockdown end of March to 16.2% a month later. In contrast, all other COVID-19-related worries, showed a (nonsignificant) decline during the same period. Conclusion:Our study supports the notion that pandemic measures have to be balanced against adverse public health effects. Especially vulnerable groups have to be protected. -19, wellbeing, worries, children, adolescents This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. K E Y W O R D S COVID

Neutrophils are thought to rely solely on nonspecific immune mechanisms. Here we provide molecular biological, immunological, ultrastructural, and functional evidence for the presence of a T cell receptor (TCR)-based variable immunoreceptor in a 5-8% subpopulation of human neutrophils. We demonstrate that these peripheral blood neutrophils express variable and individualspecific TCR␣␤ repertoires and the RAG1͞RAG2 recombinase complex. The proinflammatory cytokine granulocyte colonystimulating factor regulates expression of the neutrophil immunoreceptor and RAG1͞RAG2 in vivo. Specific engagement of the neutrophil TCR complex protects from apoptosis and stimulates secretion of the neutrophil-activating chemokine IL-8. Our results, which also demonstrate the presence of the TCR in murine neutrophils, suggest the coexistence of a variable and an innate host defense system in mammalian neutrophils.innate immune system ͉ neutrophil granulocyte ͉ T cell receptor

Current reference values of ALT, AST, and GGT serum levels were calculated for children between 11 months and 16.0 years, using modern analytical and statistical methods. This study extends the current knowledge about transaminases by revealing influences of age, sex, BMI, and puberty on serum concentrations of all three parameters and has for these parameters one of the largest sample sizes published so far. (Hepatology 2017).

The use of electronic media has increased substantially and is already observable in young children. The present study explored associations of preschoolers’ use of electronic media with age, gender, and socio-economic status, investigated time trends, and examined reciprocal longitudinal relations between children’s use of electronic media and their behavioral difficulties. The study participants included 527 German two- to six-year-old children whose parents had provided information on their use of electronic media and their behavioral difficulties at two time points, with approximately 12 months between baseline and follow-up. The analyses revealed that older vs. younger children, as well as children from families with a lower vs. higher socio-economic status, were more often reported to use electronic media. Furthermore, the usage of mobile phones increased significantly between 2011 and 2016. Most interestingly, baseline usage of computer/Internet predicted more emotional and conduct problems at follow-up, and baseline usage of mobile phones was associated with more conduct problems and hyperactivity or inattention at follow-up. Peer relationship problems at baseline, on the other hand, increased the likelihood of using computer/Internet and mobile phones at follow-up. The findings indicate that preschoolers’ use of electronic media, especially newer media such as computer/Internet and mobile phones, and their behavioral difficulties are mutually related over time.