Forever-Fit Summer Camp: The Impact of a 6-Week Summer Healthy Lifestyle Day Camp on Anthropometric, Cardiovascular, and Physical Fitness Measures in Youth With Obesity

Pediatric obesity is a public health concern with lifestyle intervention as the first-line treatment. Forever-Fit Summer Camp (FFSC) is a 6-week summer day program offering physical activity, nutrition education, and well-balanced meals to youth at low cost. The aim of the study was to assess the efficacy of this program that does not emphasize weight loss rather emphasizes healthy behaviors on body mass index, cardiovascular and physical fitness. Methods: The inclusion criteria were adolescents between 8 and 12 years and body mass index (BMI) ≥85th percentile. The data were collected at baseline and week 6 (wk-6) and was analyzed for 2013-2018 using paired-sample t tests. Results: The participants' (N = 179) average age was 10.6 ± 1.6 years with a majority of females (71%) and black race/ethnicity (70%). At wk-6, BMI and waist circumference decreased by 0.8 ± 0.7 kg/m2 and 1.0 ± 1.3 in, respectively. Resting heart rate, diastolic and systolic blood pressure decreased by 8.5 ± 11.0 bpm, 6.3 ± 8.8 mmHg, and 6.4 ± 10.1 mmHg, respectively. The number of pushups, curl-ups, and chair squats were higher by 5.8 ± 7.5, 6.7 ± 9.1, and 7.7 ± 8.5, respectively. Conclusion: The FFSC is efficacious for improving BMI, cardiovascular, and physical fitness in the short term. The effect of similar episodic efforts that implement healthy lifestyle modifications throughout the school year should be investigated

Methylomic profiling of cortex samples from completed suicide cases implicates a role for PSORS1C3 in major depression and suicide.

This is the final version of the article. Available from Nature Publishing Group via the DOI in this record.Major depressive disorder (MDD) represents a major social and economic health issue and constitutes a major risk factor for suicide. The molecular pathology of suicidal depression remains poorly understood, although it has been hypothesised that regulatory genomic processes are involved in the pathology of both MDD and suicidality. In this study, genome-wide patterns of DNA methylation were assessed in depressed suicide completers (n=20) and compared with non-psychiatric, sudden-death controls (n=20) using tissue from two cortical brain regions (Brodmann Area 11 (BA11) and Brodmann Area 25 (BA25)). Analyses focused on identifying differentially methylated regions (DMRs) associated with suicidal depression and epigenetic variation were explored in the context of polygenic risk scores for major depression and suicide. Weighted gene co-methylation network analysis was used to identify modules of co-methylated loci associated with depressed suicide completers and polygenic burden for MDD and suicide attempt. We identified a DMR upstream of the PSORS1C3 gene, subsequently validated using bisulfite pyrosequencing and replicated in a second set of suicide samples, which is characterised by significant hypomethylation in both cortical brain regions in MDD suicide cases. We also identified discrete modules of co-methylated loci associated with polygenic risk burden for suicide attempt, but not major depression. Suicide-associated co-methylation modules were enriched among gene networks implicating biological processes relevant to depression and suicidality, including nervous system development and mitochondria function. Our data suggest that there are coordinated changes in DNA methylation associated with suicide that may offer novel insights into the molecular pathology associated with depressed suicide completers.We are grateful to all of the patients and control subjects who contributed to this study. The authors would like to acknowledge support of the Brain and Behaviour Research Foundation through a NARSAD Young Investigator Grant to TMM and from the UK Medical Research Council (MRC) (grant number MR/K013807/1) to JM. ZK would like to acknowledge funding from the NIH grant (grant number NIMH 1R21MH094771). The Douglas Bell Canada Brain Bank is supported by the FRQS through the Quebec Network on Suicide, Mood Disorders and Related Disorders, and by Brain Canada through an infrastructure grant. We acknowledge Niamh Mullins and Professor Catherine Lewis, King’s College London, for kindly supplying us with the suicide attempt GWAS data

Play Across Boston: A Community Initiative to Reduce Disparities in Access to After-School Physical Activity Programs for Inner-City Youths

Background: In 1999, the Centers for Disease Control and Prevention (CDC) funded Play Across Boston to address disparities in access to physical activity facilities and programs for Boston, Mass, inner-city youths. Context: Local stakeholders worked with the Harvard School of Public Health Prevention Research Center and Northeastern University's Center for the Study of Sport in Society to improve opportunities for youth physical activity through censuses of facilities and programs and dissemination of results. Methods: Play Across Boston staff conducted a facility census among 230 public recreational complexes and a program census of 86% of 274 physical activity programs for Boston inner-city youths aged 5 to 18 years during nonschool hours for the 1999 to 2000 school year and summer of 2000. Comparison data were collected from three suburban communities: one low income, one medium income, and one high income. Consequences: Although Boston has a substantial sports and recreational infrastructure, the ratio of youths to facilities in inner-city Boston was twice the ratio found in the medium- and high-income suburban comparison communities. The low-income suburban comparison community had the highest number of youths per recreational facility with 137 youths per facility, followed by Boston with 117 youths per facility. The ratio of youths to facilities differed among Boston neighborhoods. Boston youths participated less in school-year physical activities than youths in medium- and high-income communities, and less advantaged Boston neighborhoods had lower levels of participation than more advantaged Boston neighborhoods. Girls participated less than boys. Interpretation: Play Across Boston successfully developed and implemented a rigorous needs assessment with local relevance and important implications for public health research on physical activity and the environment. Boston Mayor Thomas M. Menino called the Play Across Boston report a "playbook" for future sports and recreation planning by the city of Boston and its community partners

Dual functions of Macpiwi1 in transposon silencing and stem cell maintenance in the flatworm Macrostomum lignano

PIWI proteins and piRNA pathways are essential for transposon silencing and some aspects of gene regulation during animal germline development. In contrast to most animal species, some flatworms also express PIWIs and piRNAs in somatic stem cells, where they are required for tissue renewal and regeneration. Here, we have identified and characterized piRNAs and PIWI proteins in the emerging model flatworm Macrostomum lignano. We found that M. lignano encodes at least three PIWI proteins. One of these, Macpiwi1, acts as a key component of the canonical piRNA pathway in the germline and in somatic stem cells. Knockdown of Macpiwi1 dramatically reduces piRNA levels, derepresses transposons, and severely impacts stem cell maintenance. Knockdown of the piRNA biogenesis factor Macvasa caused an even greater reduction in piRNA levels with a corresponding increase in transposons. Yet, in Macvasa knockdown animals, we detected no major impact on stem cell self-renewal. These results may suggest stem cell maintenance functions of PIWI proteins in flatworms that are distinguishable from their impact on transposons and that might function independently of what are considered canonical piRNA populations

Systematic under-estimation of the epigenetic clock and age acceleration in older subjects

Background: The Horvath epigenetic clock is widely used. It predicts age quite well from 353 CpG sites in the DNA methylation profile in unknown samples and has been used to calculate 'age acceleration’ in various tissues and environments. Results: The model systematically underestimates age in tissues from older people. This is seen in all examined tissues but most strongly in the cerebellum and is consistently observed in multiple datasets. Age acceleration is thus age-dependent, and this can lead to spurious associations. The current literature includes examples of association tests with age acceleration calculated in a wide variety of ways. Conclusions: The concept of an epigenetic clock is compelling, but caution should be taken in interpreting associations with age acceleration. Association tests of age acceleration should include age as a covariate

A Proinflammatory Cytokine Inhibits P53 Tumor Suppressor Activity

p53 has a key role in the negative regulation of cell proliferation, in the maintenance of genomic stability, and in the suppression of transformation and tumorigenesis. To identify novel regulators of p53, we undertook two functional screens to isolate genes which bypassed either p53-mediated growth arrest or apoptosis. In both screens, we isolated cDNAs encoding macrophage migration inhibitory factor (MIF), a cytokine that was shown previously to exert both local and systemic proinflammatory activities. Treatment with MIF overcame p53 activity in three different biological assays, and suppressed its activity as a transcriptional activator. The observation that a proinflammatory cytokine, MIF, is capable of functionally inactivating a tumor suppressor, p53, may provide a link between inflammation and tumorigenesis

Short-Term Change in Measures of Glycemia in Obese Youth Meeting Criteria for Prediabetes: A Retrospective Chart Review

Background: The prevalence of youth diagnosed with prediabetes is increasing, yet there is a lack of guidelines on how to manage this condition clinically. Objectives: The aim was to determine the short-term outcomes of patients referred with prediabetes and to determine predictors of worsening dysglycemia in youth. Study Design: This is a retrospective chart review of patients referred to our Youth Diabetes Prevention Clinic (YDPC) with laboratory tests indicating an increased risk for type 2 diabetes (T2D). We defined glycemic categories by HbA1c with normoglycemia as HbA1c <5.7%, prediabetes I (P1) as HbA1c 5.7 to <6.0%, and prediabetes II (P2) as HbA1c 6.0 to <6.5%. We compared HbA1c at the time of referral (screening HbA1c) and at the YDPC visit (YDPC HbA1c) to assess for improvement or worsening. Multinomial logistic regression was used to assess predictors of prediabetes. Results: Among 562 patients seen, 336 had both screening and YDPC HbA1c values. Race (p < 0.001) and screening glycemic category (p < 0.001) were significantly associated with dysglycemia at the YDPC visit, while sex (p = 0.50), BMI z-score change (p = 0.27), and days from referral (p = 0.83) were not. As compared to those who reverted to normoglycemia, patients with prediabetes at YDPC were 7 times more likely to have a higher screening HbA1c (both P1 and P2). The majority of patients referred with prediabetes had lower HbA1c at the YDPC (75.4–82.6%). Conclusion: Patients with screening HbA1c <6% might benefit from a 4-month follow-up at primary care while recommending lifestyle changes. Patients of minority race and screening HbA1c ≥6% are more likely to have a persistent elevation of HbA1c

Functional characterization of the schizophrenia associated gene AS3MT identifies a role in neuronal development

This is the final version. Available from Wiley via the DOI in this record. DATA AVAILABILITY STATEMENT: All raw RNAseq files are available at GSE182157 and generated cell lines available on request.Genome-wide association studies (GWAS) have identified multiple genomic regions associated with schizophrenia, although many variants reside in noncoding regions characterized by high linkage disequilibrium (LD) making the elucidation of molecular mechanisms challenging. A genomic region on chromosome 10q24 has been consistently associated with schizophrenia with risk attributed to the AS3MT gene. Although AS3MT is hypothesized to play a role in neuronal development and differentiation, work to fully understand the function of this gene has been limited. In this study we explored the function of AS3MT using a neuronal cell line (SH-SY5Y). We confirm previous findings of isoform specific expression of AS3MT during SH-SY5Y differentiation toward neuronal fates. Using CRISPR-Cas9 gene editing we generated AS3MT knockout SH-SY5Y cell lines and used RNA-seq to identify significant changes in gene expression in pathways associated with neuronal development, inflammation, extracellular matrix formation, and RNA processing, including dysregulation of other genes strongly implicated in schizophrenia. We did not observe any morphological changes in cell size and neurite length following neuronal differentiation and MAP2 immunocytochemistry. These results provide novel insights into the potential role of AS3MT in brain development and identify pathways through which genetic variation in this region may confer risk for schizophrenia.Academy of Medical SciencesBiotechnology and Biological Sciences Research CouncilMedical Research CouncilMedical Research CouncilWellcome TrustWellcome TrustUniversity of Exete

Genome and transcriptome of the regeneration-competent flatworm, Macrostomum lignano.

The free-living flatworm, Macrostomum lignano has an impressive regenerative capacity. Following injury, it can regenerate almost an entirely new organism because of the presence of an abundant somatic stem cell population, the neoblasts. This set of unique properties makes many flatworms attractive organisms for studying the evolution of pathways involved in tissue self-renewal, cell-fate specification, and regeneration. The use of these organisms as models, however, is hampered by the lack of a well-assembled and annotated genome sequences, fundamental to modern genetic and molecular studies. Here we report the genomic sequence of M. lignano and an accompanying characterization of its transcriptome. The genome structure of M. lignano is remarkably complex, with ∼75% of its sequence being comprised of simple repeats and transposon sequences. This has made high-quality assembly from Illumina reads alone impossible (N50=222 bp). We therefore generated 130× coverage by long sequencing reads from the Pacific Biosciences platform to create a substantially improved assembly with an N50 of 64 Kbp. We complemented the reference genome with an assembled and annotated transcriptome, and used both of these datasets in combination to probe gene-expression patterns during regeneration, examining pathways important to stem cell function.This work is supported by National Institutes of Health Grants R37 GM062534 (to G.J.H.) and R01-HG006677 (to M.S.); National Science Foundation Grant DBI-1350041 (to M.S.); and a Swiss National Science Foundation Grant 31003A-143732 (to L.S.). This work was performed with assistance from Cold Spring Harbor Laboratory Shared Resources, which are funded, in part, by Cancer Center Support Grant 5P30CA045508.This is the final version of the article. It first appeared from PNAS via http://dx.doi.org/10.1073/pnas.151671811