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Background The aim of this study is to estimate the appropriateness of recommended dispositions made in response to calls to after hours services offering telephone triage, usually involving nurses. The setting was five local trials sponsored by the Australian government aimed at addressing problems in after hours general practice service provision. All five trials offered telephone triage though the form of this varied considerably. Methods The study was a prospective service audit. Simulated patient calls using validated patient care scenarios with different levels of clinical significance were developed by a consensus panel of experts. Sixty telephone calls were monitored by a member of the research team to assess whether provider responses were in conformity with recommended dispositions. Results Services fell well short of a 100% appropriate response rate across all five trials. Services generally performed poorly for cases with high clinical implications such as presumed meningococcal meningitis and gastroenteritis with dehydration in a child. In general, problems of undertriage were more common than overtriage. Conclusions The safety of dispositions of telephone triage services requires further study. Simulated patient calls may be more useful for quality improvement purposes than the usual method of random audit of audiotaped calls of real patients using service records. [ABSTRACT FROM AUTHOR]

Abstract Background Chemotaxis is crucial for the colonisation/infection of hosts with Campylobacter jejuni. Central to chemotaxis are the group A chemotaxis genes that are responsible for sensing the external environment. The distribution of group A chemoreceptor genes, as found in the C. jejuni sequenced strains, tlp1-4, 7, 10 and 11 were determined in 33 clinical human and avian isolates. Results Group A tlp gene content varied among the strains with genes encoding tlp1 (aspartate receptor, ccaA) and tlp7 present in all strains tested, where as tlp11 was present in only one of our international collection clinical isolates, C. jejuni 520, but was more prevalent (9/13) in the freshly isolated clinical stains from patients who required hospitalisation due to C. jejuni infection (GCH1-17). Relative expression levels of the group A tlp genes were also determined in C. jejuni reference strains NCTC 11168-GS, 11168-O and 81116 using cells grown in vitro at 37°C, 42°C and maintained at room temperature and with cells isolated directly from murine and avian hosts by immune magnetic separation without subsequent culture. Gene expression of tlp genes was varied based on strain, growth conditions and in vivo isolation source. Tlp1, although the most conserved, showed the lowest and most varied mRNA expression and protein production under laboratory conditions. Tlp7 was highly expressed at most conditions tested, and gene expression was not influenced by the tlp7 gene encoding a full length protein or one expressed as separate periplasmic and cytoplasmic domains. Conclusion We have shown that chemosensory receptor set variation exists among C. jejuni strains, but is not dependent on the isolation source.

Objective: Rare cases of monogenic obesity, which may respond to specific therapeutics, can remain undetected in populations in which polygenic obesity is prevalent. This study examined rare DNA variation in established monogenic obesity genes within a community using whole-exome sequence data from 6803 longitudinally studied individuals., Methods: Exome data across 15 monogenic obesity genes were analyzed for nonsynonymous variants observed in any child with a maximum BMI z score > 2 (N = 279) but not observed in a child with a maximum BMI z score ≤ 0 (n = 1542) or that occurred in adults in the top 5th percentile of BMI (n = 263) but not in adults below the median BMI (n = 2629). Variants were then functionally analyzed using luciferase assays., Results: The comparisons between cases of obesity and controls identified eight missense variants in six genes: DYRK1B, KSR2, MC4R, NTRK2, PCSK1, and SIM1. Among these, MC4R p.A303P and p.R165G were previously shown to impair MC4R function. Functional analyses of the remaining six variants suggest that KSR2 p.I402F and p.T193I and NTRK2 p.S249Y alter protein function., Conclusions: In addition to MC4R, rare missense variants in KSR2 and NTRK2 may potentially explain the severe obesity observed for the carriers., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Background: The role of neighborhood factors in the association between adverse childhood experiences (ACEs) and body mass index (BMI) has not been widely studied. A neighborhood ACEs index (NAI) captures neighborhood environment factors associated with ACE exposure. This study examined associations between BMI and an NAI among New York City (NYC) youth. An exploratory objective examined the NAI geographic distribution across NYC neighborhoods. Methods: Data for students attending NYC public general education schools in kindergarten-12th grade from 2006-2017 ( n = 1,753,867) were linked to 25 geospatial datasets capturing neighborhood characteristics for every census tract in NYC. Multivariable hierarchical linear regression tested associations between BMI and the NAI; analyses also were conducted by young (<8 years), school age (8-12 years), and adolescent (>12 years) subgroups. In addition, NAI was mapped by census tract, and local Moran's I identified clusters of high and low NAI neighborhoods. Results: Higher BMI was associated with higher NAI across all sex and age groups, with largest magnitude of associations for girls (medium NAI vs. low NAI: unstandardized β = 0.112 (SE 0.008), standardized β [effect size]=0.097, p < 0.001; high NAI vs. low NAI: unstandardized β = 0.195 (SE 0.008), standardized β = 0.178, p < 0.001) and adolescents (medium NAI vs. low NAI: unstandardized β = 0.189 (SE 0.014), standardized β = 0.161, p < 0.001, high NAI vs. low NAI: unstandardized β = 0.364 (SE 0.015), standardized β = 0.334, p < 0.001 for adolescent girls; medium NAI vs. low NAI: unstandardized β = 0.122 (SE 0.014), standardized β = 0.095, p < 0.001, high NAI vs. low NAI: unstandardized β = 0.217 (SE 0.015), standardized β = 0.187, p < 0.001 for adolescent boys). Each borough of NYC included clusters of neighborhoods with higher and lower NAI exposure, although clusters varied in size and patterns of geographic dispersion across boroughs. Conclusions: A spatial index capturing neighborhood environment factors associated with ACE exposure is associated with higher BMI among NYC youth. Findings complement prior literature about relationships between neighborhood environment and obesity risk, existing research documenting ACE-obesity associations, and the potential for neighborhood factors to be a source of adversity. Collectively, evidence suggests that trauma-informed place-based obesity reduction efforts merit further exploration as potential means to interrupt ACE-obesity associations.

Background: Fewer than 1/4th of US children and adolescents meet physical activity (PA) guidelines, leading to health disparities that track into adulthood. Neighborhood opportunity may serve as a critical modifiable factor to improve fitness attainment and reduce these disparities. We drew data from the Child Opportunity Index to examine associations between neighborhood indicators of opportunity for PA and multiple fitness indicators among New York City public school youth. Methods: Multilevel generalized linear mixed models were used to estimate the overall and sex-stratified associations between neighborhood indicators (green space, healthy food, walkability, commute time) and indicators for physical fitness [curl-ups, push-ups, Progressive Aerobic Cardiovascular Endurance Run (PACER), sit-and-reach] using the New York City FITNESSGRAM data set. Results: The analytic sample [ n  = 299,839; median (interquartile range) age = 16 (12-17)] was 50.1% female, 37.5% Hispanic, 26.2% non-Hispanic Black, and most (69.5%) qualified for free/reduced price school meals. Neighborhood indicators were positively associated with higher values of indicators for physical fitness. The strongest associations were observed between walkability and both BMI and PACER, and commute time with BMI, push-ups, and PACER. For example, walkability had the greatest magnitude of effects for BMI and muscular strength and endurance (BMI: β : -0.75, 95% confidence interval, CI: -1.01 to -0.49; PACER: β : 1.98, 95% CI: 1.59 to 2.37), and particularly for girls compared with boys (BMI, girls: β : -0.91, 95% CI: -1.22 to -0.66); BMI, boys: β : -0.56, 95% CI: -0.86 to -0.25); PACER, girls: β : 2.11, 95% CI: 1.68 to 2.54; push-ups, boys: β : 1.71, 95% CI: 1.31 to 2.12). Conclusion: Neighborhood indicators were associated with multiple measures of youth fitness. Continued research on neighborhood opportunity and youth fitness may better inform place-based public health interventions to reduce disparities.

Recent national trends in the United States indicate a significant increase in childhood obesity, a major public health concern with documented physical and mental comorbidities and sociodemographic disparities. We aimed to estimate the prevalence of obesity and severe obesity among youth in New York City (NYC) before the COVID-19 pandemic and examine time trends overall and by key characteristics. We included all valid height and weight measurements of kindergarten through 8th grade public school students aged 5 to 15 from school years 2011-12 through 2019-20 (N = 1,370,890 unique students; 5,254,058 observations). Obesity and severe obesity were determined using age- and sex-specific body mass index percentiles based on the Centers for Disease Control and Prevention growth charts. Analyses were performed using multivariate logistic regression models with repeated cross-sectional observations weighted to represent the student population for each year and clustered by student and school. Among youth attending public elementary and middle schools in NYC, we estimate that 20.9% and 6.4% had obesity and severe obesity, respectively, in 2019-20. While consistent declines in prevalence were observed overall from 2011-12 to 2019-20 (2.8% relative decrease in obesity and 0.2% in severe obesity, p<0.001), increasing trends were observed among Black, Hispanic, and foreign-born students, suggesting widening disparities. Extending previous work reporting prevalence estimates in this population, nearly all groups experienced significant increases in obesity and severe obesity from 2016-17 to 2019-20 (relative change = 3.5% and 6.7%, respectively, overall; p<0.001). Yet, some of the largest increases in obesity were observed among those already bearing the greatest burden, such as Black and Hispanic students and youth living in poverty. These findings highlight the need for greater implementation of equity-centered obesity prevention efforts. Future research should consider the influence of the COVID-19 pandemic and changes in clinical guidance on childhood obesity and severe obesity in NYC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Purpose: This paper aims to examine the association between asthma severity and one-year lagged fitness in New York City Public school youth by neighborhood opportunity., Methods: Using the Child Opportunity Index 2.0 and individual-level repeated measures NYC Office of School Health (OSH) fitness surveillance data (2010-2018), we ran multilevel mixed models stratified by neighborhood opportunity, adjusting for sex, race/ethnicity, grade level, poverty status, and time. Asthma severity was based on a physician-completed Asthma Medication Administration Form (MAF) from each school year and drawn from the Automated Student Health Record (ASHR)., Results: Across all youth in grades 4-12 (n = 939,598; 51.7 % male; 29.9 % non-Hispanic Black, 39.3 % Hispanic; 70.0 % high poverty), lower neighborhood opportunity was associated with lower subsequent fitness. Youth with severe asthma and very low and low neighborhood opportunity had the lowest 1-year lagged fitness z-scores - 0.24 (95 % CI, -0.34 to -0.14) and - 0.26 (95 % CI, -0.32 to -0.20), respectively, relative to youth with no asthma and very high opportunity., Conclusions: An inverse longitudinal relationship between asthma severity and subsequent fitness was observed. Study findings have implications for public health practitioners to promote physical activity and improved health equity for youth with asthma, taking neighborhood factors into account., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

ABSTRACT Smiles provide information about a social partner's affect and intentions during social interaction. Although always encountered within a specific situation, the influence of contextual information on smile evaluation has not been widely investigated. Moreover, little is known about the reciprocal effect of smiles on evaluations of their accompanying situations. In this research, we assessed how different smile types and situational contexts affected participants' social evaluations. In Study 1, 85 participants rated reward, affiliation, and dominance smiles embedded within either enjoyable, polite, or negative (unpleasant) situations. Context had a strong effect on smile ratings, such that smiles in enjoyable situations were rated as more genuine and joyful, as well as indicating less superiority than those in negative situations. In Study 2, 200 participants evaluated the situations that these smiles were perceived within (rather than the smiles themselves). Although situations paired with reward (vs. affiliation) smiles tended to be rated more positively, this effect was absent for negative situations. Ultimately, the findings point toward a reciprocal relationship between smiles and contexts, whereby the face influences evaluations of the situation and vice versa.

Vaccination is an indispensable tool to reduce negative outcomes due to COVID-19. Although COVID-19 disproportionately affected lower income and Black and Hispanic communities, these groups have had lower population-level uptake of vaccines. Using detailed cross-sectional data, we examined racial and ethnic group differences in New York City schoolchildren becoming fully vaccinated (two doses) within 6 months of vaccine eligibility. We matched school enrollment data to vaccination data in the Citywide Immunization Registry, a census of all vaccinations delivered in New York City. We used ordinary least squares regression models to predict fully vaccinated status, with key predictors of race and ethnicity using a variety of different control variables, including residential neighborhood or school fixed effects. We also stratified by borough and by age. The sample included all New York City public school students enrolled during the 2021-2022 school year. Asian students were most likely to be vaccinated and Black and White students least likely. Controlling for student characteristics, particularly residential neighborhood or school attended, diminished some of the race and ethnicity differences. Key differences were also present by borough, both overall and by racial and ethnic groups. In sum, racial and ethnic disparities in children's COVID-19 vaccination were present. Vaccination rates varied by the geographic unit of borough; controlling for neighborhood characteristics diminished some disparities by race and ethnicity. Neighborhood demographics and resources, and the attributes, culture and preferences of those who live there may affect vaccination decisions and could be targets of future efforts to increase vaccination rates., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Neighborhood environments can support fitness-promoting behavior, yet little is known about their influence on youth physical fitness outcomes over time. We examined longitudinal associations between neighborhood opportunity and youth physical fitness among New York City (NYC) public school youth. The Child Opportunity Index (COI), a composite index of 29 indicators measuring neighborhood opportunity at the census-tract level, along with scores on 4 selected COI indicators were linked to NYC FITNESSGRAM youth data at baseline. Fitness outcomes (measured annually, 2011-2018) included body mass index, curl-ups, push-ups, and Progressive Aerobic Cardiovascular Endurance Run (PACER) laps. Unstratified and age-stratified, adjusted, 3-level generalized linear mixed models, nested by census tract and time, estimated the association between COI and fitness outcomes. The analytical sample (n = 204,939) lived in very low (41%) or low (30%) opportunity neighborhoods. Unstratified models indicated that overall COI is modestly associated with improved youth physical fitness outcomes. The strongest opportunity-fitness associations were observed for PACER. Stratified models show differences in associations across younger vs. older youth. We find that neighborhood factors are associated with youth fitness outcomes over time, with the strength of the associations dependent on age. Future implications include better informed place-based interventions tailored to specific life stages to promote youth health., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study assessed associations between school nurse workload and student health and academic outcomes. We hypothesized that lower school nurse workload would be associated with better student outcomes, with associations being greater for members of groups who experience health disparities. Our methods entailed secondary analysis of data for New York City school students in kindergarten through 12th grade during 2015-2016 ( N = 1,080,923), using multilevel multivariate regression as the analytic approach. Results demonstrated lower school nurse workload was associated with better outcomes for student participation in asthma education but not chronic absenteeism, early dismissals, health office visits, immunization compliance, academic achievement, or overweight/obesity. Our findings suggest school nurses may influence proximal outcomes, such as participation in disease-related education, more easily than downstream outcomes, such as absenteeism or obesity. While contrary to our hypotheses, results align with the fact that school nurses deliver community-based, population health-focused care that is inherently complex, multilevel, and directly impacted by social determinants of health. Future research should explore school nurses' perspectives on what factors influence their workload and how they can best impact student outcomes.

Severe persistent childhood asthma is associated with low physical activity and may be associated with poor physical fitness. Research on the asthma severity-fitness association longitudinally and across sociodemographic subgroups is needed to inform fitness interventions targeting youth with asthma. We evaluated the relationship between asthma severity (categorized as severe, mild, or no asthma) and subsequent fitness in New York City (NYC) public school youth enrolled in grades 4-12 using the NYC Fitnessgram dataset (2010-2018). Longitudinal mixed models with random intercepts were fit to test the association between asthma severity and one-year lagged fitness z-scores by clustering repeated annual observations at the student level. Models were adjusted for sex, race/ethnicity, grade level, poverty status, time, and stratified by sociodemographic factors. The analytic sample included 663,137 students (51% male; 31% non-Hispanic Black, 40% Hispanic; 55% in grades 4-8, 70% high poverty; 87%, 11% and 1% with no, mild, and severe asthma, respectively). Students with severe asthma and mild asthma demonstrated -0.19 (95% CI, -0.20 to -0.17) and - 0.10 (95% CI, -0.11 to -0.10), respectively, lower fitness z-scores in the subsequent year relative to students without asthma. After stratifying by demographics, the magnitude of the asthma severity-fitness relationship was highest for non-Hispanic white vs. all other racial/ethnic subgroups, and was similar across sex, grade level, and household poverty status. Overall, we observed an inverse longitudinal relationship between asthma severity and subsequent fitness among urban youth, particularly non-Hispanic Whites. Future research should examine how neighborhood-level factors impact the asthma severity-fitness relationship across racial/ethnic subgroups., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Child weight status is inversely associated with fitness, but less is known about this relationship across fitness domains. This study examined the longitudinal association between weight status and fitness domains in a large, diverse sample of children. Methods: Data were drawn from the New York City Fitnessgram (2010-2011 to 2017-2018). Height and weight were collected annually and converted to weight status using Centers for Disease Control and Prevention growth charts. Aerobic capacity, muscular strength, and endurance were measured as age and sex standardized z -scores based on the fitness performance tests. Repeated-measures multilevel models were run testing the association between weight status and 1-year lagged fitness domains. Results: The sample included 917,554 children (51.8% male, 39.3% Hispanic, 29.9% non-Hispanic Black, 13.9%, 4.7%, and 1.7% class I, II, and III obesity, respectively). For each fitness domain, fitness scores decreased with increasing weight status across all demographic categories, with the lowest fitness scores observed in children with the most severe obesity, and highest magnitude of effects for aerobic capacity, and particularly among boys, non-Hispanic Whites, and older youth. For example, compared with youth with healthy weight, youth with overweight had 0.28 standard deviation lower aerobic capacity performance [confidence interval (95% CI): -0.29 to -0.28], followed by class 1 obesity ( β  = -0.57, 95% CI: -0.58 to -0.57), class 2 obesity ( β  = -0.88, 95% CI: -0.88 to -0.88), and class 3 obesity ( β  = -1.19, 95% CI: -1.20 to -1.18). Conclusions: Compared with youth with healthy weight, youth at every other weight status had lower subsequent fitness, with the magnitude of the relationship increasing as weight status increased. Future research should examine interventions targeting aerobic capacity to reduce fitness disparities.

NYC FITNESSGRAM, monitored by the New York City (NYC) Department of Education and the NYC Department of Health and Mental Hygiene, functions as the NYC Department of Education's citywide youth fitness surveillance program. Here we present the methods, characteristics, and data used in this surveillance system to monitor physical fitness in public school students (grades kindergarten through 12; initiated in 2006; n = 6,748,265 observations; mean sample of 519,097 observations per year to date) in New York, New York. Youth physical fitness prevalence estimates, longitudinal trends, and spatial analyses may be investigated using continuous fitness composite percentile scores and Cooper Institute for Aerobic Research-defined sex- and age-specific Healthy Fitness Zones. Healthy Fitness Zones are based on individual-child fitness test performance, with standard errors clustered at the school and student levels and adjusted for sociodemographic characteristics. Results may be used to show trends in youth fitness attainment over time and highlight disparities in the fitness prevalence of NYC students. In sum, continuous fitness composite percentile scores offer the opportunity for prospective tracking of shifts in youth physical fitness on a population scale and across subpopulations. NYC FITNESSGRAM can accompany a growing body of surveillance tools demonstrating the potential for population-level surveillance tools to promote global public health., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Obesity is associated with poorer youth fitness. However, little research has examined the magnitude of this relationship in youth with severe obesity. Therefore, we sought to determine the relationship between increasing weight status and fitness within a sample of children and adolescents from New York City public schools., Methods: This study utilized longitudinal data from the NYC Fitnessgram dataset years 2010-2018. Height and weight along with fitness were measured annually during physical education classes. Severity of obesity was defined using body mass index relative to the 95th percentile and then categorized into classes. A composite measure of fitness was calculated based on scores for three fitness tests: aerobic capacity, muscular strength, and muscular endurance. To examine the weight status-fitness relationship, repeated measures mixed models with random-intercepts were constructed. Stratified models examined differences by demographic factors., Results: The sample included 917,554 youth (51.8% male, 39.3% Hispanic, 29.9% non-Hispanic Black, 14.0%, 4.6%, and 1.6% class I, II and III obesity, respectively). Compared to youth with healthy weight, increasing severity of obesity was associated with decreased fitness: overweight (β = - 0.28, 95% CI:-0.29;-0.28), class I obesity (β = - 0.60, 95% CI:-0.60; - 0.60), class II obesity (β = - 0.94, 95% CI:-0.94; - 0.93), and class III obesity (β = - 1.28; 95% CI:-1.28; - 1.27). Stratified models showed the association was stronger among male and non-Hispanic White youth., Conclusion: Findings revealed that more severe obesity was associated with lower fitness. Future research is needed to develop targeted interventions to improve fitness in youth with obesity., (© 2023. The Author(s).)

Introduction: Research showing that place of birth (POB) predicts excess weight gain and obesity risk among Latino adults has not prompted similar research in Latino children, although childhood is a critical period for preventing obesity. Objective: To identify differences in obesity risk among Latino children by POB. Methods: Longitudinal cohort observational study on public school children self-identified by parent/guardian as Latino in grades K-12 for school years 2006-07 through 2016-17 with measured weight and height ( n  = 570,172 students ; 3,103,642 observations ). POB reported by parent/guardian was categorized as continental United States [not New York City (NYC)] ( n  = 295,693), NYC ( n  = 166,361), South America ( n  = 19,452), Central America ( n  = 10,241), Dominican Republic ( n  = 57,0880), Puerto Rico ( n  = 9687), and Mexico ( n  = 9647). Age- and sex-specific BMI percentiles were estimated based on established growth charts. Data were analyzed in 2020. Results: Prevalence of obesity was highest among US (non-NYC)-born girls (21%) and boys (27%), followed by NYC-born girls (19%) and boys (25%). Among girls, South Americans (9%) had the lowest prevalence of all levels of obesity, while Puerto Ricans (19%) and Dominicans (15%) had the highest prevalence. Among boys, South Americans also had the lowest prevalence of all levels of obesity (15%), while Puerto Ricans (22%) and Mexicans (21%) had the highest. In adjusted models, obesity risk was highest in US (non-NYC)-born children, followed by children born in NYC ( p  < 0.001). Immigrant Latino children exhibited an advantage even after controlling for individual and neighborhood sociodemographic features, particularly Dominicans, South Americans, and Puerto Ricans. Conclusions: The heterogeneity of obesity risk among Latino children highlights the importance of POB.

Skeletal muscle is highly plastic and dynamically regulated by the body's physical demands. This study aimed to determine the plasticity of skeletal muscle DNA methylation in response to 8 weeks of supervised exercise training in volunteers with a range of insulin sensitivities. We studied 13 sedentary participants and performed euglycemic hyperinsulinemic clamps with basal vastus lateralis muscle biopsies and peak aerobic activity (VO2 peak) tests before and after training. We extracted DNA from the muscle biopsies and performed global methylation using Illumina's Methylation EPIC 850K BeadChip. Training significantly increased peak aerobic capacity and insulin-stimulated glucose disposal. Fasting serum insulin and insulin levels during the steady state of the clamp were significantly lower post-training. Insulin clearance rates during the clamp increased following the training. We identified 13 increased and 90 decreased differentially methylated cytosines (DMCs) in response to 8 weeks of training. Of the 13 increased DMCs, 2 were within the following genes, FSTL3 , and RP11-624M8.1 . Of the 90 decreased DMCs, 9 were within the genes CNGA1 , FCGR2A , KIF21A , MEIS1 , NT5DC1 , OR4D1 , PRPF4B , SLC26A7 , and ZNF280C . Moreover, pathway analysis showed an enrichment in metabolic and actin-cytoskeleton pathways for the decreased DMCs, and for the increased DMCs, an enrichment in signal-dependent regulation of myogenesis, NOTCH2 activation and transmission, and SMAD2/3: SMAD4 transcriptional activity pathways. Our findings showed that 8 weeks of exercise training alters skeletal muscle DNA methylation of specific genes and pathways in people with varying degrees of insulin sensitivity.

Aims and Context: This paper reports the evaluation of the Doorway program (2015-18) in Melbourne, Australia. Doorway extends the original Housing First (HF) model in providing housing support to people with precarious housing at-risk of homelessness with Serious and Persistent Mental Illnesses (SPMIs) receiving care within Victoria's public mental health system. Doorway participants source and choose properties through the open rental market, and receive rental subsidies, assistance, advocacy and brokerage support through their Housing and Recovery Worker (HRW). The aim of this study is to estimate Doorway's impact on participants' housing, quality of life and mental health service use., Methodology: The study employed a a quasi-experimental study design with a comparison group, adjusted for ten potential confounders. The primary outcome measure was days of secure housing per participant. Secure housing status, health service usage and quality of life (HoNOS) data were extracted from participants' electronic hospital and Doorway records in deidentified, non-reidentifiable form. Analysis for continuous outcome variables was based on multivariate GLM modelling., Results: Doorway housed 89 (57%) of 157 accepted participants. The 157 Doorway participants overall were also housed for significantly more days (119.4 extra days per participant) than control participants, albeit after some delay in locating and moving into housing (mean 14 weeks). There was a significant, positive Doorway effect on health outcomes (all and one dimension of the HoNOS). Doorway participants had significantly reduced length of stay during acute and community hospital admissions (7.4 fewer days per participant) compared with the control group., Conclusion: The Doorway model represents a new and substantial opportunity to house, enhance health outcomes and reduce mental health service use for people with SPMIs from the public mental health sector and at-risk of homelessness.

Objective: This study aimed to identify genetic variants enriched in Southwest American Indian (SWAI) individuals that associate with BMI., Methods: Whole genome sequencing data (n = 296) were used to identify potentially functional variants that are common in SWAI individuals (minor allele frequency ≥10%) but rare in other ethnic groups (minor allele frequency < 0.1%). Enriched variants were tested for association with BMI in 5,870 SWAI individuals. One variant was studied using a luciferase reporter, and haplotypes that included this variant were analyzed for association with various measures of obesity (n = 917-5,870), 24-hour energy expenditure (24-h EE; n = 419), and skeletal muscle biopsy expression data (n = 207)., Results: A 5' untranslated region variant in cytochrome b5 type A (CYB5A), rs548402150, met the enrichment criteria and associated with increased BMI (β = 2%, p = 0.004). Functionally, rs548402150 decreased luciferase expression by 30% (p = 0.003) and correlated with decreased skeletal muscle CYB5A expression (β = -0.5 SD, p = 0.0008). Combining rs548402150 with two splicing quantitative trait loci in CYB5A identified a haplotype carried almost exclusively in SWAI individuals that associated with increased BMI (β = 3%, p = 0.0003) and decreased CYB5A expression, whereas the most common haplotype in all ethnic groups associated with lower BMI and percentage of body fatness, increased 24-h EE, and increased CYB5A expression., Conclusions: Further studies on the effects of CYB5A on 24-h EE and BMI may provide insights into obesity-related physiology., (Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society (TOS).)

The Office of School Health, a joint program of the Departments of Health and Education, administers New York City's (NYC) body mass index (BMI) surveillance system to monitor childhood obesity. We describe the context, importance, and process for creating a multi-agency, school-based BMI surveillance system using BMI collected from annual FITNESSGRAM® physical fitness assessments conducted as part of a larger physical activity and wellness curriculum in NYC public schools. We also summarize our current system and methodology, highlighting the types of data and data sources that comprise the system and partnership between the Departments of Health and Education that enable data sharing. Strategies for addressing threats to data quality, including missing data, biologically implausible values, and imprecise/subjective weight or height equipment are discussed. We also review current and future surveillance data products, and provide recommendations for collecting, analyzing, interpreting, and reporting BMI data for childhood obesity surveillance. Collaboration between Departments of Health and Education as well as attention to safeguards of BMI reporting and data quality threats have enabled NYC to collect high quality BMI data to accurately monitor childhood obesity trends. These findings have implications for youth BMI surveillance systems in the United States and globally., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

FITNESSGRAM® is the most widely used criterion-referenced tool to assess/report on student health-related fitness across the US. Potential weight-related biases with the two most common tests of musculoskeletal fitness-the trunk extension and Back-Saver Sit-and-Reach (sit-and-reach)-have been hypothesized, though have not been studied. To determine the association between musculoskeletal fitness test performance and weight status, we use data from 571,133 New York City public school 4th-12th grade students (85% non-White; 75% qualified for free or reduced-price meals) with valid/complete 2017-18 FITNESSGRAM® data. Adjusted logistic mixed effects models with a random effect for school examined the association between weight status and whether a student was in the Healthy Fitness Zone (HFZ; met sex- and age-specific criterion-referenced standards) for the trunk extension and sit-and-reach. Compared to students with normal weight, the odds of being in the HFZ for trunk extension were lower for students with underweight (OR = 0.77; 95% CI: 0.741, 0.795) and higher for students with overweight (OR = 1.10; 95% CI: 1.081, 1.122) and obesity (OR = 1.11; 95% CI: 1.090, 1.13). The odds of being in the HFZ for sit-and-reach were lower for students with underweight OR = 0.85; 95% CI: 0.826, 0.878), overweight (OR = 0.83; 95% CI: 0.819, 0.844) and obesity (OR = 0.65; 95% CI: 0.641, 0.661). Students with overweight and obesity perform better on the trunk extension, yet worse on the sit-and-reach, compared to students with normal weight. Teachers, administrators, and researchers should be aware of the relationship of BMI with student performance in these assessments., Competing Interests: Dr. Andjelka Pavlovic, Ph.D. is the Director of Research and Education in the Division of Youth Education for the Cooper Institute, which is responsible for the FITNESSGRAM®. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The mechanisms of weight loss and metabolic improvements following bariatric surgery in skeletal muscle are not well known; however, epigenetic modifications are likely to contribute. The aim of our study was to investigate skeletal muscle DNA methylation after weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Muscle biopsies were obtained basally from seven insulin-resistant obese (BMI > 40 kg/m 2 ) female subjects (45.1 ± 3.6 years) pre- and 3-month post-surgery with euglycemic hyperinsulinemic clamps to assess insulin sensitivity. Four lean (BMI < 25 kg/m 2 ) females (38.5 ± 5.8 years) served as controls. We performed reduced representation bisulfite sequencing next generation methylation on DNA isolated from the vastus lateralis muscle biopsies., Results: Global methylation was significantly higher in the pre- (32.97 ± 0.02%) and post-surgery (33.31 ± 0.02%) compared to the lean (30.46 ± 0.02%), P < 0.05. MethylSig analysis identified 117 differentially methylated cytosines (DMCs) that were significantly altered in the post- versus pre-surgery (Benjamini-Hochberg q < 0.05). In addition, 2978 DMCs were significantly altered in the pre-surgery obese versus the lean controls (Benjamini-Hochberg q < 0.05). For the post-surgery obese versus the lean controls, 2885 DMCs were altered (Benjamini-Hochberg q < 0.05). Seven post-surgery obese DMCs were normalized to levels similar to those observed in lean controls. Of these, 5 were within intergenic regions (chr11.68,968,018, chr16.73,100,688, chr5.174,115,531, chr5.1,831,958 and chr9.98,547,011) and the remaining two DMCs chr17.45,330,989 and chr14.105,353,824 were within in the integrin beta 3 (ITGB3) promoter and KIAA0284 exon, respectively. ITGB3 methylation was significantly decreased in the post-surgery (0.5 ± 0.5%) and lean controls (0 ± 0%) versus pre-surgery (13.6 ± 2.7%, P < 0.05). This decreased methylation post-surgery was associated with an increase in ITGB3 gene expression (fold change + 1.52, P = 0.0087). In addition, we showed that ITGB3 promoter methylation in vitro significantly suppressed transcriptional activity (P < 0.05). Transcription factor binding analysis for ITGB3 chr17.45,330,989 identified three putative transcription factor binding motifs; PAX-5, p53 and AP-2alphaA., Conclusions: These results demonstrate that weight loss after RYGB alters the epigenome through DNA methylation. In particular, this study highlights ITGB3 as a novel gene that may contribute to the metabolic improvements observed post-surgery. Future additional studies are warranted to address the exact mechanism of ITGB3 in skeletal muscle.

Objective: In an ongoing effort to identify the genetic variation that contributes to obesity in American Indians, known Bardet-Biedl syndrome (BBS) genes were analyzed for an effect on BMI and leptin signaling., Methods: Potentially deleterious variants (Combined Annotation Dependent Depletion score > 20) in BBS genes were identified in whole-exome sequence data from 6,851 American Indians informative for BMI. Common variants (detected in ≥ 10 individuals) were analyzed for association with BMI; rare variants (detected in < 10 individuals) were analyzed for mean BMI of carriers. Functional assessment of variants' effect on signal transducer and activator of transcription 3 (STAT3) activity was performed in vitro., Results: One common variant, rs59252892 (Thr549Ile) in BBS9, was associated with BMI (P = 0.0008, β = 25% increase per risk allele). Among rare variants for which carriers had severe obesity (mean BMI > 40 kg/m 2 ), four were in BBS9. In vitro analysis of BBS9 found the Ile allele at Thr549Ile had a 20% increase in STAT3 activity compared with the Thr allele (P = 0.01). Western blot analysis showed the Ile allele had a 15% increase in STAT3 phosphorylation (P = 0.006). Comparable functional results were observed with Ser545Gly and Val209Leu but not Leu665Phe and Lys810Glu., Conclusions: Potentially functional variants in BBS genes in American Indians are reported. However, functional evidence supporting a causal role for BBS9 in obesity is inconclusive., (© 2021 Regeneron Pharmaceuticals Inc. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Standardized physical fitness monitoring provides a more accurate proxy for youth health when compared with physical activity. Little is known about the utilization of broad-scale individual-level youth physical fitness testing to explore health disparities. We examined longitudinal trends in population-level fitness for 4th-12th grade New York City youth during 2006/7-2016/17 (average n = 510,293 per year). Analyses were performed in 2019. The primary outcome was whether or not youth achieved sex-/age-specific performance levels (called the Healthy Fitness Zone) on the aerobic capacity, muscular strength and muscular endurance tests using the NYC FITNESSGRAM. The Cooper Institute's most recent Healthy Fitness Zone criteria were applied to all tests and years. Prevalence estimates were weighted, accounted for school clustering, adjusted for student-level sociodemographics, and run by sociodemographic subgroups and year. The overall prevalence for meeting 3 Healthy Fitness Zones increased from 15.5% (95%CI: 13.9%-17.0%) in 2006/7 to 23.3% (95%CI: 22.2%-24.4%) in 2016/17 for students in grades 4-12. Fitness for all student groups increased over time, although Hispanic and non-Hispanic black girls consistently had the lowest prevalence of meeting 3 Healthy Fitness Zones as compared to all other race/sex subgroups. Also, 9th-12th graders had a lower prevalence of meeting 3 Healthy Fitness Zones as compared to 4th-8th graders. Given forecasted sharp increases in cardiovascular disease prevalence, routine youth fitness surveillance using standardized, criterion referenced methods can identify important fitness disparities and inform interventions., Competing Interests: The authors have declared that no competing interests exist.

Objective: This study aimed to estimate population-level prevalence of obesity and severe obesity for New York City youth and examine the most recent trends over time., Methods: All public school youth in grades kindergarten through eighth (K-8) (2011-2012 through 2016-2017) with valid weight and height measures were included (N = 1,137,782 unique students; 3,720,297 observations). Age- and sex-specific BMI percentiles for obesity and severe obesity were estimated using Centers for Disease Control and Prevention growth charts. Repeated cross-sectional analyses were conducted using logistic regression, weighting for missing or invalid responses and accounting for clustering by students and schools to examine trends over time and by sociodemographics., Results: Among youth in K-8 (aged 5-15 years, 48.8% girls), the prevalence of obesity and severe obesity in 2011-2012 was 21.5% and 6.4%, respectively, compared with 20.2% and 6.0%, respectively, in 2016-2017. Since 2011-2012, decreasing trends in obesity and severe obesity (relative declines: 6.0% and 6.3%, respectively, P < 0.001) have been observed. Significant decreases were observed for all subgroups (P < 0.001), although there remained disparities in relative declines over time by race/ethnicity and poverty., Conclusions: Decreasing trends in obesity and severe obesity among all New York City K-8 public school youth are promising; however, persistent disparities highlight the need to improve intervention design and implementation strategies for groups disproportionately burdened by obesity., (© 2020 The Obesity Society.)

Recent research demonstrates that youth fitness improvements are associated with lower absenteeism. This study assessed whether the effects of poverty on the longitudinal fitness-absenteeism relationship are consistent across poverty measures at the student, school, and neighborhood levels and across sex in New York City (NYC) public school youth individually followed over 4 years. Negative binomial longitudinal mixed models with random-intercepts were developed stratified by five dichotomized student, school and neighborhood poverty measures and sex to test the change in fitness-lagged absenteeism relationship in six cohorts of NYC middle school students (2006/7-2012/13). Models were adjusted for individual-level race/ethnicity, place of birth, change in obesity status, grade, time, and school size. The sample included 360,743 students (51% male, 39% Hispanic, 28% non-Hispanic black, 69% qualifying for free/reduced price school meals). Adjusted estimates showed an inverse dose-response fitness-absenteeism relationship in high poverty youth across all poverty measures, including the student, school and neighborhood levels. For example, in girls exposed to high poverty based on school neighborhood, absenteeism decreased by 11.3% (IRR = -0.12, 95% CI: -0.20, -0.04), 10.4% (IRR = -0.11, 95% CI: -0.21, -0.02), 6.8% (IRR = -0.07, 95% CI: -0.14, 0.00) and 4.9% (IRR = -0.05, 95% CI: -0.15, 0.04) for students who had a >20% increase, 10-20% increase, <10% change, and 10-20% decrease in fitness from the prior year, respectively, relative to the reference group (>20% decrease in fitness). Future research should explore the impact of tailored interventions for youth that aim to promote youth physical activity at each of the individual, school and neighborhood levels, and particularly among high poverty subgroups., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Extensive research demonstrates the benefits of fitness on children's health and academic performance. Although decreases in health-related fitness may increase school absenteeism, multiple years of prospective, child-level data are needed to examine whether fitness changes predict subsequent chronic absenteeism status., Methods: Six cohorts of New York City public school students were followed from grades 5-8 (2006/2007-2012/2013; N = 349,381). A longitudinal 3-level logistic generalized linear mixed model with random intercepts was used to test the association of individual children's changes in fitness and 1-year lagged chronic absenteeism., Results: The odds of chronic absenteeism increased 27% [odds ratio (OR) 95% confidence interval (CI), 1.25-1.30], 15% (OR 95% CI, 1.13-1.18), 9% (OR 95% CI, 1.07-1.11), and 1% (OR 95% CI, 0.98-1.04), for students who had a >20% decrease, 10%-20% decrease, <10% increase or decrease, and 10%-20% increase in fitness, respectively, compared with >20% fitness increase., Conclusion: These findings contribute important longitudinal evidence to a cross-sectional literature, demonstrating reductions in youth fitness may increase absenteeism. Given only 25% of youth aged 12-15 years achieve the recommended daily 60 minutes or more of moderate to vigorous physical activity, future work should examine the potential for youth fitness interventions to reduce absenteeism and foster positive attitudes toward lifelong physical activity.

Purpose: One-fifth to one-third of students in high poverty, urban school districts do not attend school regularly (missing ≥6 days/year). Fitness is shown to be associated with absenteeism, although this relationship may differ across poverty and gender subgroups., Methods: Six cohorts of New York City public school students were followed up from grades 5 to 8 during 2006/2007-2012/2013 (n = 349,381). Stratified three-level longitudinal generalized linear mixed models were used to test the association between changes in fitness and 1-year lagged child-specific days absent across gender and poverty., Results: In girls attending schools in high/very high poverty areas, greater improvements in fitness the prior year were associated with greater reductions in absenteeism (P = .034). Relative to the reference group (>20% decrease in fitness composite percentile scores from the prior year), girls with a large increase in fitness (>20%) demonstrated 10.3% fewer days absent (incidence rate ratio [IRR] 95% confidence interval [CI]: 0.834, 0.964), followed by those who had a 10%-20% increase in fitness (9.2%; IRR 95% CI: 0.835, 0.987), no change (5.4%; IRR 95% CI: 0.887, 1.007), and a 10%-20% decrease in fitness (3.8%; IRR 95% CI: 0.885, 1.045). In girls attending schools in low/mid poverty areas, fitness and absenteeism also had an inverse relationship, but no clear trend emerged. In boys, fitness and absenteeism had an inverse relationship but was not significant in either poverty group., Conclusions: Fitness improvements may be more important to reducing absenteeism in high/very high poverty girls compared with low/mid poverty girls and both high/very high and low/mid poverty boys. Expanding school-based physical activity programs for youth particularly in high poverty neighborhoods may increase student attendance., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Youth health-related fitness positively affects academic outcomes, although limited research has focused on the relationship between fitness and school absenteeism. We examined the longitudinal association between individual children's fitness and lagged school absenteeism over 4 years in urban middle schools., Methods: Six cohorts of New York City public school students were followed from grades 5 through 8 (school years 2006-2007 through 2012-2013; n = 349,381). A 3-level longitudinal generalized linear mixed model was used to test the association of change in fitness composite percentile scores and 1-year lagged child-specific days absent., Results: Adjusted 3-level negative binomial models showed that students with a more than 20% increase, 10% to 20% increase, less than 10% increase or decrease, and 10% to 20% decrease in fitness from the year prior had 11.9% (95% confidence interval [CI], 7.2-16.8), 6.1% (95% CI, 1.0-11.4), 2.6% (95% CI, -1.1 to 6.5), and 0.4% (95% CI, -4.3 to 5.4) lower absenteeism compared with students with a more than 20% fitness decrease., Conclusion: Cumulative effects of fitness improvement could have a significant impact on child absenteeism over time, particularly in high-need subgroups. Future research should examine the potential for school-based fitness interventions to reduce absenteeism rates, particularly for youths who have fitness drop-offs in adolescence.

Background: Obesity is a disease that is caused by genetic and environmental factors. However, epigenetic mechanisms of obesity are less well known. DNA methylation provides a mechanism whereby environmental factors can influence gene transcription. The aim of our study was to investigate skeletal muscle DNA methylation of sorbin and SH3 domain containing 3 ( SORBS3 ) with weight loss induced by Roux-en-Y gastric bypass (RYGB)., Results: Previously, we had shown increased methylation (5.0 to 24.4%) and decreased gene expression (fold change - 1.9) of SORBS3 with obesity (BMI > 30 kg/m 2 ) compared to lean controls. In the present study, basal muscle biopsies were obtained from seven morbidly obese (BMI > 40 kg/m 2 ) female subjects pre- and 3 months post-RYGB surgery, in combination with euglycemic-hyperinsulinemic clamps to assess insulin sensitivity. We identified 30 significantly altered promoter and untranslated region methylation sites in SORBS3 using reduced representation bisulfite sequencing (RRBS). Twenty-nine of these sites were decreased (- 5.6 to - 24.2%) post-RYGB compared to pre-RYGB. We confirmed the methylation in 2 (Chr.8:22,423,690 and Chr.8:22,423,702) of the 29 decreased SORBS3 sites using pyrosequencing. This decreased methylation was associated with an increase in SORBS3 gene expression (fold change + 1.7) post-surgery. In addition, we demonstrated that SORBS3 promoter methylation in vitro significantly alters reporter gene expression ( P  < 0.0001). Two of the SORBS3 methylation sites (Chr.8:22,423,111 and Chr.8:22,423,205) were strongly correlated with fasting plasma glucose levels ( r  = 0.9, P  = 0.00009 and r  = 0.8, P  = 0.0010). Changes in SORBS3 gene expression post-surgery were correlated with obesity measures and fasting insulin levels ( r  = 0.5 to 0.8; P  < 0.05)., Conclusions: These results demonstrate that SORBS3 methylation and gene expression are altered in obesity and restored to normal levels through weight loss induced by RYGB surgery.

Maximal safe resection has long been the cornerstone of treatment for WHO grade I benign meningioma. However, as technology for both imaging and radiation delivery has advanced, radiation therapy has played an increasingly important role in the management of patients with WHO grade I meningioma. Radiation therapy, whether delivered as standard fractionated treatment over several weeks, stereotactic radiosurgery over 1 session, or multisession stereotactic radiation therapy, has been shown to provide excellent local control when used as an adjunct to surgery or as primary treatment. Here, we review the indications for radiation therapy for patients with WHO grade I meningioma, as well as the various techniques that have been developed. We also review the toxicities and late effects associated with treatment.

Obesity can increase the risk of complex metabolic diseases, including insulin resistance. Moreover, obesity can be caused by environmental and genetic factors. However, the epigenetic mechanisms of obesity are not well defined. Therefore, the identification of novel epigenetic biomarkers of obesity allows for a more complete understanding of the disease and its underlying insulin resistance. The aim of our study was to identify DNA methylation changes in whole-blood that were strongly associated with obesity and insulin resistance. Whole-blood was obtained from lean (n = 10; BMI = 23.6 ± 0.7 kg/m 2 ) and obese (n = 10; BMI = 34.4 ± 1.3 kg/m 2 ) participants in combination with euglycemic hyperinsulinemic clamps to assess insulin sensitivity. We performed reduced representation bisulfite sequencing on genomic DNA isolated from the blood. We identified 49 differentially methylated cytosines (DMCs; q < 0.05) that were altered in obese compared with lean participants. We identified 2 sites (Chr.21:46,957,981 and Chr.21:46,957,915) in the 5' untranslated region of solute carrier family 19 member 1 (SLC19A1) with decreased methylation in obese participants (lean 0.73 ± 0.11 vs. obese 0.09 ± 0.05; lean 0.68 ± 0.10 vs. obese 0.09 ± 0.05, respectively). These 2 DMCs identified by obesity were also significantly predicted by insulin sensitivity (r = 0.68, P = 0.003; r = 0.66; P = 0.004). In addition, we performed a differentially methylated region (DMR) analysis and demonstrated a decrease in methylation of Chr.21:46,957,915-46,958,001 in SLC19A1 of -34.9% (70.4% lean vs. 35.5% obese). The decrease in whole-blood SLC19A1 methylation in our obese participants was similar to the change observed in skeletal muscle (Chr.21:46,957,981, lean 0.70 ± 0.09 vs. obese 0.31 ± 0.11 and Chr.21:46,957,915, lean 0.72 ± 0.11 vs. obese 0.31 ± 0.13). Pyrosequencing analysis further demonstrated a decrease in methylation at Chr.21:46,957,915 in both whole-blood (lean 0.71 ± 0.10 vs. obese 0.18 ± 0.06) and skeletal muscle (lean 0.71 ± 0.10 vs. obese 0.30 ± 0.11). Our findings demonstrate a new potential epigenetic biomarker, SLC19A1, for obesity and its underlying insulin resistance.

Physical fitness in children has many beneficial effects, including the maintenance of a healthy weight. The built environment may influence youths' physical fitness by encouraging physical activity. This paper assessed whether higher density of parks, playgrounds, and sports facilities around a school is related to improvements in fitness in middle school boys and girls. Fitness scores and other student covariates collected as part of NYC FITNESSGRAM between the 2006-2007 and 2010-2011 school years were linked with school neighborhood data on characteristics of the built environment for NYC public school students in grades 6-8. Data were analyzed in 2015. Medium, but not high, density of recreational resources in the area surrounding a school was associated with greater annual improvements in fitness for both boys and girls. This association appeared to be driven mainly by the presence of parks. Findings for sports facilities and playgrounds were inconsistent. Overall, few associations were observed between recreational resources near a school and changes in student fitness. Future studies of school influences on student fitness should consider the influence of school resources and the home neighborhood.

The mechanisms of metabolic improvements after Roux-en-Y gastric bypass (RYGB) surgery are not entirely clear. Therefore, the aim of our study was to investigate the role of obesity and RYGB on the human skeletal muscle proteome. Basal muscle biopsies were obtained from seven obese (BMI >40 kg/m(2)) female subjects (45.1 ± 3.6 years) pre- and 3 months post-RYGB, and euglycemic-hyperinsulinemic clamps were used to assess insulin sensitivity. Four age-matched (48.5 ± 4.7 years) lean (BMI <25 kg/m(2)) females served as control subjects. We performed quantitative mass spectrometry and microarray analyses on protein and RNA isolated from the muscle biopsies. Significant improvements in fasting plasma glucose (104.2 ± 7.8 vs. 86.7 ± 3.1 mg/dL) and BMI (42.1 ± 2.2 vs. 35.3 ± 1.8 kg/m(2)) were demonstrated in the pre- versus post-RYGB, both P < 0.05. Proteomic analysis identified 2,877 quantifiable proteins. Of these, 395 proteins were significantly altered in obesity before surgery, and 280 proteins differed significantly post-RYGB. Post-RYGB, 49 proteins were returned to normal levels after surgery. KEGG pathway analysis revealed a decreased abundance in ribosomal and oxidative phosphorylation proteins in obesity, and a normalization of ribosomal proteins post-RYGB. The transcriptomic data confirmed the normalization of the ribosomal proteins. Our results provide evidence that obesity and RYGB have a dynamic effect on the skeletal muscle proteome., (© 2016 by the American Diabetes Association.)

Background: Obesity is a metabolic disease caused by environmental and genetic factors. However, the epigenetic mechanisms of obesity are incompletely understood. The aim of our study was to investigate the role of skeletal muscle DNA methylation in combination with transcriptomic changes in obesity., Results: Muscle biopsies were obtained basally from lean (n = 12; BMI = 23.4 ± 0.7 kg/m(2)) and obese (n = 10; BMI = 32.9 ± 0.7 kg/m(2)) participants in combination with euglycemic-hyperinsulinemic clamps to assess insulin sensitivity. We performed reduced representation bisulfite sequencing (RRBS) next-generation methylation and microarray analyses on DNA and RNA isolated from vastus lateralis muscle biopsies. There were 13,130 differentially methylated cytosines (DMC; uncorrected P < 0.05) that were altered in the promoter and untranslated (5' and 3'UTR) regions in the obese versus lean analysis. Microarray analysis revealed 99 probes that were significantly (corrected P < 0.05) altered. Of these, 12 genes (encompassing 22 methylation sites) demonstrated a negative relationship between gene expression and DNA methylation. Specifically, sorbin and SH3 domain containing 3 (SORBS3) which codes for the adapter protein vinexin was significantly decreased in gene expression (fold change -1.9) and had nine DMCs that were significantly increased in methylation in obesity (methylation differences ranged from 5.0 to 24.4 %). Moreover, differentially methylated region (DMR) analysis identified a region in the 5'UTR (Chr.8:22,423,530-22,423,569) of SORBS3 that was increased in methylation by 11.2 % in the obese group. The negative relationship observed between DNA methylation and gene expression for SORBS3 was validated by a site-specific sequencing approach, pyrosequencing, and qRT-PCR. Additionally, we performed transcription factor binding analysis and identified a number of transcription factors whose binding to the differentially methylated sites or region may contribute to obesity., Conclusions: These results demonstrate that obesity alters the epigenome through DNA methylation and highlights novel transcriptomic changes in SORBS3 in skeletal muscle.

Background: Socioeconomic status (SES) impacts health outcomes. The Youth Risk Behavior Survey (YRBS), like many school-based data sources, lacks individual-level poverty information. We propose using school-level percentages of student eligibility for free/reduced-price meals (%FRPM) as a proxy for individual-level poverty., Methods: Using the New York City (NYC) 2009 YRBS, we created school-level poverty quartiles to append to individual YRBS records by ranking schools by %FRPM. We compared this with 2 other school-level poverty measures using students' home and school neighborhood-level poverty and measured the association of these 3 school-level proxies with individual's household income. Last, we evaluated health outcomes by race/ethnicity and poverty to demonstrate the importance of accounting for poverty., Results: The school-level measure that used %FRPM had the strongest association with household income. When the school-level individual poverty proxy was included in illustrative analyses using YRBS data, patterns by poverty within race/ethnicity emerged that were not seen when looking at race/ethnicity alone., Conclusions: Using a poverty measure to analyze school-based data will provide a better understanding of the impact of SES on health outcomes. Based on our evaluation, when individual-level information is not available, we propose using school-level %FRPM, which are publicly available throughout the United States., (© 2016, American School Health Association.)

Carbonic anhydrase buffers tissue pH by catalyzing the rapid interconversion of carbon dioxide (CO2) and bicarbonate (HCO3 (-)). We assessed the functional activity of CAIX in two colorectal tumor models, expressing different levels of the enzyme, by measuring the rate of exchange of hyperpolarized (13)C label between bicarbonate (H(13)CO3(-)) and carbon dioxide ((13)CO2), following injection of hyperpolarized H(13)CO3(-), using (13)C-magnetic resonance spectroscopy ((13)C-MRS) magnetization transfer measurements. (31)P-MRS measurements of the chemical shift of the pH probe, 3-aminopropylphosphonate, and (13)C-MRS measurements of the H(13)CO3(-)/(13)CO2 peak intensity ratio showed that CAIX overexpression lowered extracellular pH in these tumors. However, the (13)C measurements overestimated pH due to incomplete equilibration of the hyperpolarized (13)C label between the H(13)CO3(-) and (13)CO2 pools. Paradoxically, tumors overexpressing CAIX showed lower enzyme activity using magnetization transfer measurements, which can be explained by the more acidic extracellular pH in these tumors and the decreased activity of the enzyme at low pH. This explanation was confirmed by administration of bicarbonate in the drinking water, which elevated tumor extracellular pH and restored enzyme activity to control levels. These results suggest that CAIX expression is increased in hypoxia to compensate for the decrease in its activity produced by a low extracellular pH and supports the hypothesis that a major function of CAIX is to lower the extracellular pH., (©2015 American Association for Cancer Research.)

Purpose: To evaluate whether a change in fitness is associated with academic outcomes in New York City (NYC) middle-school students using longitudinal data and to evaluate whether this relationship is modified by student household poverty., Methods: This was a longitudinal study of 83,111 New York City middle-school students enrolled between 2006-2007 and 2011-2012. Fitness was measured as a composite percentile based on three fitness tests and categorized based on change from the previous year. The effect of the fitness change level on academic outcomes, measured as a composite percentile based on state standardized mathematics and English Language Arts test scores, was estimated using a multilevel growth model. Models were stratified by sex, and additional models were tested stratified by student household poverty., Results: For both girls and boys, a substantial increase in fitness from the previous year resulted in a greater improvement in academic ranking than was seen in the reference group (girls: .36 greater percentile point improvement, 95% confidence interval: .09-.63; boys: .38 greater percentile point improvement, 95% confidence interval: .09-.66). A substantial decrease in fitness was associated with a decrease in academics in both boys and girls. Effects of fitness on academics were stronger in high-poverty boys and girls than in low-poverty boys and girls., Conclusions: Academic rankings improved for boys and girls who increased their fitness level by >20 percentile points compared to other students. Opportunities for increased physical fitness may be important to support academic performance., (Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Although studies have shown that childhood obesity overall is on the decline among New York City (NYC) public school children, the prevalence of severe childhood obesity has not been studied., Methods: We used height and weight measurements of 947,765 NYC public school students aged 5 to 14 years in kindergarten through 8th grade (K-8), from school years 2006-07 through 2010-11. We used age- and sex-specific body mass index (BMI) percentiles according to Centers for Disease Control and Prevention growth charts to define childhood obesity (BMI ≥ 95th percentile) and severe childhood obesity (BMI ≥120% of 95th percentile) and to identify biologically implausible values (BIV). Multivariable logistic models tested for trends in obesity and severe obesity prevalence. To evaluate misclassification, we recalculated prevalence estimates for the most recent school year (2010-11) including the student records identified as BIV who were also declared severely obese (BMI ≥ 120% of 95th percentile). We refer to this subgroup of BIVs as "high BIV.", Results: Severe obesity among NYC public school students in grades K-8 decreased 9.5% from the 2006-07 school year (6.3%) to the 2010-11 school year (5.7%), and obesity decreased 5.5% (from 21.9% to 20.7%). The prevalence of severe obesity and obesity was highest among minority, poor, and male children. Severe obesity declined in prevalence among every subgroup, with the greatest effect among white students and wealthy students. Severe obesity prevalence increased with age, and obesity prevalence peaked among those aged 7 to 10 years. For the 2010-11 school year, including high BIVs increased severe obesity prevalence from 5.7% to 6.6% and increased obesity prevalence from 20.7% to 21.5%., Conclusion: Among all subgroups of NYC public school children in grades K-8, the reduction in severe obesity was greater than the reduction in overall obesity. Efforts to decrease obesity in NYC have affected the severely obese; however, monitoring of this specific subgroup should continue because of differences in trends and greater health risks.

Induced bulk orientation of nematic liquid crystal in contact with micron-scale patterned surfaces is investigated using the Landau-de Gennes theory by means of three-dimensional simulations. The effect of the size and spacing of square cross-sectional well and post patterns is investigated and shown to influence the orientation of the liquid crystal bulk, far removed from the surface. Additionally, the effective anchoring strength of the induced alignment is estimated using a modified version of the torque balance method. Both azimuthal and zenithal multistability are shown to exist within unique ranges of feature sizes.

A stereocontrolled synthesis of norphenyl hyperolactone C together with its utility as a direct precursor to the anti-HIV agent hyperolactone C and analogues by addition of organolithiums, are described. Preliminary studies to access this key building block in a catalytic enantioselective manner are also reported.