The hidden burden of eating disorders : an extension of estimates from the Global Burden of Disease Study 2019

Background: Anorexia nervosa and bulimia nervosa are the only eating disorders included in the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, yet binge-eating disorder and other specified feeding or eating disorder (OSFED) are more prevalent. This study sought to estimate the prevalence and burden of binge-eating disorder and OSFED globally and present a case for their inclusion in GBD. Methods: We sourced studies from the GBD 2019 anorexia nervosa and bulimia nervosa epidemiological databases, two systematic reviews that included studies with epidemiological estimates of binge-eating disorder and OSFED, and experts in the field. Studies, published between Jan 1, 1998, and March 1, 2019, were included if they reported non-zero prevalence of two or more eating disorders (anorexia nervosa, bulimia nervosa, binge-eating disorder, or OSFED) and diagnosed cases according to DSM-IV or DSM-5. The proportions of total eating disorder cases that met diagnostic criteria for each individual eating disorder were estimated via network meta-regression and simulation using studies reporting eating disorder prevalence. The global cases unrepresented in GBD 2019 were estimated using the proportions from the simulation and the GBD 2019 eating disorder prevalence. Disability weights for binge-eating disorder and OSFED were then estimated along with disability-adjusted life-years (DALYs). Estimates are presented with 95% uncertainty intervals (UIs). Findings: 54 studies, of which 36 were from high-income countries, were included in the analysis. The number of global eating disorder cases in 2019 that were unrepresented in GBD 2019 was 41·9 million (95% UI 27·9–59·0), and consisted of 17·3 million (11·3–24·9) people with binge-eating disorder and 24·6 million (14·7–39·7) people with OSFED (vs 13·6 million [10·2–17·5] people with eating disorders in GBD 2019). Together, binge-eating disorder and OSFED caused 3·7 million (95% UI 2·0–6·5) DALYs globally, bringing the total eating disorder DALYs to 6·6 million (3·8–10·6) in 2019. Interpretation: Binge-eating disorder and OSFED accounted for the majority of eating disorder cases and DALYs globally. These findings warrant the inclusion of binge-eating disorder and OSFED in future iterations of GBD, which will bring the burden experienced by people living with these disorders to the attention of policy makers with the means to target this burden. Funding: Queensland Health, Australian National Health and Medical Research Council, and Bill & Melinda Gates Foundation

Earlier onset of tumoral anglogenesis in matrix metalloproteinase-19-deficient mice

Among matrix metalloproteinases (MMP), MMP-19 displays unique structural features and tissue distribution. In contrast to most MMPs, MMP-19 is expressed in normal human epidermis and down-regulated during malignant transformation and dedifferentiation. The contribution of MMP-19 during tumor angiogenesis is presently unknown. In an attempt to give new insights into MMP-19 in vivo functions, angiogenic response of mutant mice lacking MMP-19 was analyzed after transplantation of murine malignant PDVA keratinocytes and after injection of Matrigel supplemented with basic fibroblast growth factor. In situ hybridization and immunohistochemical analysis revealed that MMP-19 is produced by host mesenchymal cells but not by endothelial capillary cells or CD11b-positive inflammatory cells. Based on a new computer-assisted method of quantification, we provide evidence that host MMP-19 deficiency was associated with an increased early angiogenic response. In addition, increased tumor invasion was observed in MMP-19-/- mice. We conclude that, in contrast to most MMPs that promote tumor progression, MMP-19 is a negative regulator of early steps of tumor angiogenesis and invasion. These data highlight the requirement to understand the individual functions of each MMP to improve anticancer strategies

Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (P-Bonferroni <1.06 x 10(-7)). In additional analyses in 7,278 participants,Peer reviewe

The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects

The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.Peer reviewe

Comparison of smoking-related DNA methylation between newborns from prenatal exposure and adults from personal smoking.

Aim: Cigarette smoking influences DNA methylation genome wide, in newborns from pregnancy exposure and in adults from personal smoking. Whether a unique methylation signature exists for in utero exposure in newborns is unknown. Materials & methods: We separately meta-analyzed newborn blood DNA methylation (assessed using Illumina450k Beadchip), in relation to sustained maternal smoking during pregnancy (9 cohorts, 5648 newborns, 897 exposed) and adult blood methylation and personal smoking (16 cohorts, 15907 participants, 2433 current smokers). Results & conclusion: Comparing meta-analyses, we identified numerous signatures specific to newborns along with many shared between newborns and adults. Unique smoking-associated genes in newborns were enriched in xenobiotic metabolism pathways. Our findings may provide insights into specific health impacts of prenatal exposure on offspring

The lymphatic ring assay: a 3D-culture model of lymphangiogenesis.

peer reviewedLymphangiogenesis, the formation of new lymphatic vessels, is associated to numerous pathologies1 and understanding the molecular and cellular basis of this complex process is essential for the development of novel therapeutic strategies. Studies on lymphangiogenesis have been hampered by difficulties in culturing lymphatic capillaries as three-dimensional (3D) structures in vitro that mimic the in vivo features of lymphatic vessels and lymphangiogenesis. The lymphatic ring assay described here phenocopies the different steps of lymphangiogenesis, including the spreading from a preexisting vessel, cell proliferation, migration and differentiation into capillaries. It consists on the adaptation of the aortic ring assay that has proved to be useful to investigate the molecular basis of angiogenesis2-4. The lymphatic ring model is an ideal assay for testing the activity of lymphangiogenic agonists or antagonists. The absence of inflammatory cells allows a simple interpretation of results and the determination of direct effects of compounds on lymphatic endothelial cell properties. Another advantage of the lymphatic ring assay is that cell outgrowing are primary cells which have not been modified by repeated passages or immortalization. This culture model bridges the gap between in vitro and in vivo studies and allows genetic analysis by using thoracic ducts from genetically modified mice

DNA Methylation in Newborns and Maternal Smoking in Pregnancy:Genome-wide Consortium Meta-analysis

Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value &lt;2.2 x 10(-16)). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.</p