Metal availability shapes early life microbial ecology and community succession.

The gut microbiota plays a critical role in human health and disease. Microbial community assembly and succession early in life are influenced by numerous factors. In turn, assembly of this microbial community is known to influence the host, including immune system development, and has been linked to outcomes later in life. To date, the role of host-mediated nutritional immunity and metal availability in shaping microbial community assembly and succession early in life has not been explored in depth. Using a human infant cohort, we show that the metal-chelating protein calprotectin is highly abundant in infants. Taxa previously shown to be successful early colonizers of the infant gut, such as Enterococcus, Enterobacteriaceae, and Bacteroides, are highly resistant to experimental metal starvation in culture. Lactobacillus, meanwhile, is highly susceptible to metal restriction, pointing to a possible mechanism by which host-mediated metal limitation shapes the fitness of early colonizing taxa in the infant gut. We further demonstrate that formula-fed infants harbor markedly higher levels of metals in their gastrointestinal tract compared to breastfed infants. Formula-fed infants with high levels of metals harbor distinct microbial communities compared to breastfed infants, with higher levels of Enterococcus, Enterobacter, and Klebsiella, taxa which show increased resistance to the toxic effects of high metal concentrations. These data highlight a new paradigm in microbial community assembly and suggest an unappreciated role for nutritional immunity and dietary metals in shaping the earliest colonization events of the microbiota.IMPORTANCEEarly life represents a critical window for microbial colonization of the human gastrointestinal tract. Surprisingly, we still know little about the rules that govern the successful colonization of infants and the factors that shape the success of early life microbial colonizers. In this study, we report that metal availability is an important factor in the assembly and succession of the early life microbiota. We show that the host-derived metal-chelating protein, calprotectin, is highly abundant in infants and successful early life colonizers can overcome metal restriction. We further demonstrate that feeding modality (breastmilk vs formula) markedly impacts metal levels in the gut, potentially influencing microbial community succession. Our work suggests that metals, a previously unexplored aspect of early life ecology, may play a critical role in shaping the early events of microbiota assembly in infants.

Barriers to and facilitators of physical activity in pediatric pulmonary hypertension.

Therapeutic exercise has not been widely adopted in pediatric pulmonary hypertension (PH), despite adult data supporting its safety and efficacy. While physical limitations may prevent children with PH from participating in physical activity, other barriers to and facilitators of physical activity are unknown. Youth ages 8-18 years with World Symposium of PH diagnostic Groups 1-4, functional class I or II, and ambulatory status were prospectively enrolled in a cross-sectional study including separate 30-min participant and caregiver interviews regarding attitudes toward physical activity and a proposed exercise intervention in pediatric PH. Interview questions were guided by Social Cognitive Theory and explored autonomy, self-confidence, and self-efficacy. Interviews were transcribed, coded, and analyzed using an iterative process to determine themes and patterns. Demographics and relevant PH condition-specific data were abstracted from the medical record. Thirty PH participant/caregiver dyads were interviewed. Facilitators of physical activity included enjoyment/interest in the activity, socialization, incentivization, and feelings of safety and normalcy. Barriers to physical activity included lack of interest, fear/anxiety, and self-consciousness. Findings were similar in children and adults. Participants rarely reported restriction of activity by caregivers or medical providers. Attitudes toward engagement in a proposed exercise program were generally positive and reflected personal experiences with physical activity. Monitored exercise interventions that focus on patients' interests, cultivate confidence, respect limitations, and acknowledge the need for extrinsic incentivization may have benefits in pediatric PH. Future trials should test the impact of these characteristics on patient wellbeing and clinical outcomes.

The Cross-Sectional Relation of Body Mass Index to Adiposity among 8- to 19-Year-Olds within Several Races and Ethnicities.

OBJECTIVE: To assess the screening ability of a high body mass index (BMI) for high adiposity among 8- to 19-year-olds. STUDY DESIGN: This cross-sectional study included 6454 National Health and Nutrition Survey participants from 2011 through 2018. Fat and lean mass were measured with dual-energy X-ray absorptiometry (DXA). We expressed adiposity as fat mass index (FMI, kg ÷ m2) and %fat. RESULTS: Based on the Centers for Disease Control and Prevention 95th percentile, a high BMI correctly classified a high FMI for about 95% of participants in each racial and ethnic group. About 81% (Blacks) to 90% (Hispanics) of participants with a high BMI also had a high FMI. Further, children with a high BMI were 17 (Hispanics) to 46 (Blacks) times more likely to have a high FMI than those with a "normal" BMI. The screening ability of high BMI for high %fat was weaker because levels of %fat are influenced by both fat mass (numerator) and lean mass (denominator). CONCLUSIONS: Despite differences in body composition, a high BMI is a very good screening tool for identifying high FMI not only among White 8- to 19-year-olds but also among Asians, Blacks, and Hispanics. Compared with %fat, FMI is likely a better adiposity metric among children and adolescents.

Alendronate preserves bone mineral density in adults with sickle cell disease and osteoporosis.

Low bone mineral density is highly prevalent in sickle cell disease (SCD); whether bisphosphonates can safely preserve or increase bone mass in SCD adults remains unknown. In this study, lumbar spine bone density remained stable with alendronate use, and treatment-related side effects were mostly mild and self-limited. PURPOSE: To describe the effects of alendronate in adults with sickle cell disease (SCD) and osteoporosis. METHODS: We reviewed retrospective clinical data from adults with SCD and osteoporosis treated with alendronate at a single center in Brazil (2009-2019). Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) of the lumbar spine, femoral neck, and total hip. We analyzed BMD changes by alendronate treatment duration (months), stratified by sex, skeletal site, and SCD genotype. RESULTS: Sixty-four SCD adults with osteoporosis (69% females, 73% HbSS, mean age ± standard deviation 42.4 ± 10.9 years) received alendronate for a median (interquartile range) of 48 (29, 73) months. Compared with males, females had significantly lower baseline BMD (g/cm2) at the femoral neck (0.72 vs 0.85, p = < 0.001) and total hip (0.79 vs 0.88, p = 0.009). The between-sex differences in BMD changes were insignificant. Mean lumbar spine BMD significantly changed by 0.0357 g/cm2 (p = 0.028) in those on alendronate for > 5 years. Four adults (6.3%) reported mild therapy-related side effects. An atypical femoral diaphysis fracture, attributed to alendronate, was incidentally noted in a 37-year-old man on treatment for 4 years. CONCLUSION: In this retrospective cohort of adults with SCD and osteoporosis on alendronate for a median of 48 months, we found no significant interactions between sex and changes in lumbar spine, femoral neck, or total hip BMD with alendronate. Lumbar spine BMD was stable in those on alendronate for < 5 years. Side effects of alendronate were mild, though one patient developed an atypical femoral fracture.

3D chromatin-based variant-to-gene maps across 57 human cell types reveal the cellular and genetic architecture of autoimmune disease susceptibility.

A portion of the genetic basis for many common autoimmune disorders has been uncovered by genome-wide association studies (GWAS), but GWAS do not reveal causal variants, effector genes, or the cell types impacted by disease-associated variation. We have generated 3D genomic datasets consisting of promoter-focused Capture-C, Hi-C, ATAC-seq, and RNA-seq and integrated these data with GWAS of 16 autoimmune traits to physically map disease-associated variants to the effector genes they likely regulate in 57 human cell types. These 3D maps of gene cis-regulatory architecture are highly powered to identify the cell types most likely impacted by disease-associated genetic variation compared to 1D genomic features, and tend to implicate different effector genes than eQTL approaches in the same cell types. Most of the variants implicated by these cis-regulatory architectures are highly trait-specific, but nearly half of the target genes connected to these variants are shared across multiple autoimmune disorders in multiple cell types, suggesting a high level of genetic diversity and complexity among autoimmune diseases that nonetheless converge at the level of target gene and cell type. Substantial effector gene sharing led to the common enrichment of similar biological networks across disease and cell types. However, trait-specific pathways representing potential areas for disease-specific intervention were identified. To test this, we pharmacologically validated squalene synthase, a cholesterol biosynthetic enzyme encoded by the FDFT1 gene implicated by our approach in MS and SLE, as a novel immunomodulatory drug target controlling inflammatory cytokine production by human T cells. These data represent a comprehensive resource for basic discovery of gene cis-regulatory mechanisms, and the analyses reported reveal mechanisms by which autoimmune-associated variants act to regulate gene expression, function, and pathology across multiple, distinct tissues and cell types.

Creating a digital approach for promoting physical activity in pediatric pulmonary hypertension: A framework for future interventions.

Children with pulmonary hypertension (PH) often demonstrate limited exercise capacity. Data support exercise as an effective nonpharmacologic intervention among adults with PH. However, data on exercise training in children and adolescents are limited, and characteristics of the optimal exercise program in pediatric PH have not been identified. Exercise programs may have multiple targets, including muscle deficits which are associated with exercise limitations in both adult and pediatric PH. Wearable accelerometer sensors measure physical activity volume and intensity in the naturalistic setting and can facilitate near continuous data transfer and bidirectional communication between patients and the study team when paired with informatics tools during exercise interventions. To address the knowledge gaps in exercise training in pediatric PH, we designed a prospective, single arm, nonrandomized pilot study to determine feasibility and preliminary estimates of efficacy of a 16-week home exercise intervention, targeting lower extremity muscle mass and enriched by wearable mobile health technology. The exercIse Training in pulmONary hypertEnsion (iTONE) trial includes (1) semistructured exercise prescriptions tailored to the participant's baseline level of activity and access to resources; (2) interval goal setting fostering self-efficacy; (3) real time monitoring of activity via wearable devices; (4) a digital platform enabling communication and feedback between participant and study team; (5) multiple avenues to assess participant safety. This pilot intervention will provide information on the digital infrastructure needed to conduct home-based exercise interventions in PH and will generate important preliminary data on the effect of exercise interventions in youth with chronic cardiorespiratory conditions to power larger studies in the future.

Shared and unique 3D genomic features of substance use disorders across multiple cell types.

Recent genome-wide association studies (GWAS) have revealed shared genetic components among alcohol, opioid, tobacco and cannabis use disorders. However, the extent of the underlying shared causal variants and effector genes, along with their cellular context, remain unclear. We leveraged our existing 3D genomic datasets comprising high-resolution promoter-focused Capture-C/Hi-C, ATAC-seq and RNA-seq across >50 diverse human cell types to focus on genomic regions that coincide with GWAS loci. Using stratified LD regression, we determined the proportion of genomewide SNP heritability attributable to the features assayed across our cell types by integrating recent GWAS summary statistics for the relevant traits: alcohol use disorder (AUD), tobacco use disorder (TUD), opioid use disorder (OUD) and cannabis use disorder (CanUD). Statistically significant enrichments (P<0.05) were observed in 14 specific cell types, with heritability reaching 9.2-fold for iPSC-derived cortical neurons and neural progenitors, confirming that they are crucial cell types for further functional exploration. Additionally, several pancreatic cell types, notably pancreatic beta cells, showed enrichment for TUD, with heritability enrichments up to 4.8-fold, suggesting genomic overlap with metabolic processes. Further investigation revealed significant positive genetic correlations between T2D with both TUD and CanUD (FDR<0.05) and a significant negative genetic correlation with AUD. Interestingly, after partitioning the heritability for each cell type's cis-regulatory elements, the correlation between T2D and TUD for pancreatic beta cells was greater (r=0.2) than the global genetic correlation value. Our study provides new genomic insights into substance use disorders and implicates cell types where functional follow-up studies could reveal causal variant-gene mechanisms underpinning these disorders.

Screening Accuracy of BMI for Adiposity Among 8- to 19-Year-Olds.

BACKGROUND AND OBJECTIVES: Although the limitations of BMI have long been recognized, there are recent concerns that it is not a good screening tool for adiposity. We therefore examined the cross-sectional relation of BMI to adiposity among 6923 8- to 19-year-olds in the National Health and Nutrition Survey from 2011 through 2018. METHODS: Participants were scanned with dual-energy x-ray absorptiometry. Adiposity was expressed as fat mass index (FMI, fat mass kg ÷ m2) and percentage of body fat (%fat). Lean mass was expressed as lean mass index (LMI, lean mass ÷ m2). Regression models and 2 × 2 tables were used to assess the relation of BMI to FMI, %fat, and LMI. RESULTS: Age and BMI accounted (R2) for 90% to 94% of the variability of FMI and LMI in each sex. Associations with %fat were weaker (R2s ∼0.70). We also examined the screening abilities of a BMI ≥ Centers for Disease Control and Prevention 95th percentile for high levels of adiposity and LMI. Cut points were chosen so that prevalences of high values of these variables would be similar to that for high BMI. Of participants with a high BMI, 88% had a high FMI, and 76% had a high %fat. Participants with a high BMI were 29 times more likely to have a high FMI than those with lower BMIs; comparable relative risks were 12 for high %fat and 14 for high LMI. CONCLUSIONS: Despite its limitations, a high BMI is a very good screening tool for identifying children and adolescents with elevated adiposity.

Environmental Phenols and Growth in Infancy: The Infant Feeding and Early Development Study.

CONTEXT: Higher mean and rapid increases in body mass index (BMI) during infancy are associated with subsequent obesity and may be influenced by exposure to endocrine-disrupting chemicals such as phenols. OBJECTIVE: In a prospective US-based cohort conducted 2010-2014, we investigated associations between environmental phenol exposures and BMI in 199 infants. METHODS: We measured seven urinary phenols at ages 6-8 and 12 weeks and assessed BMI z-score at up to 12 study visits between birth and 36 weeks. We examined individual and joint associations of averaged early infancy phenols with level of BMI z-score using mean differences (ß [95% confidence intervals (CI)]) and with BMI z-score trajectories using relative risk ratios (RR [95% CI]). RESULTS: Benzophenone-3, methyl and propyl paraben, and all phenols jointly were positively associated with higher mean BMI z-score (0.07 [-0.05, 0.18], 0.10 [-0.08, 0.27], 0.08 [-0.09, 0.25], 0.17 [-0.08, 0.43], respectively). Relative to a Stable trajectory, benzophenone-3, 2,4-dichlorophenol, 2,5-dichlorophenol, and all phenols jointly were positively associated with risk of a Rapid Increase trajectory (1.46 [0.89, 2.39], 1.33 [0.88, 2.01], 1.66 [1.03, 2.68], 1.41 [0.71, 2.84], respectively). CONCLUSION: Early phenol exposure was associated with a higher mean and rapid increase in BMI z-score across infancy, signaling potential long-term cardiometabolic consequences of exposure.

GWAS-informed data integration and non-coding CRISPRi screen illuminate genetic etiology of bone mineral density.

Over 1,100 independent signals have been identified with genome-wide association studies (GWAS) for bone mineral density (BMD), a key risk factor for mortality-increasing fragility fractures; however, the effector gene(s) for most remain unknown. Informed by a variant-to-gene mapping strategy implicating 89 non-coding elements predicted to regulate osteoblast gene expression at BMD GWAS loci, we executed a single-cell CRISPRi screen in human fetal osteoblast 1.19 cells (hFOBs). The BMD relevance of hFOBs was supported by heritability enrichment from cross-cell type stratified LD-score regression involving 98 cell types grouped into 15 tissues. 24 genes showed perturbation in the screen, with four (ARID5B, CC2D1B, EIF4G2, and NCOA3) exhibiting consistent effects upon siRNA knockdown on three measures of osteoblast maturation and mineralization. Lastly, additional heritability enrichments, genetic correlations, and multi-trait fine-mapping revealed that many BMD GWAS signals are pleiotropic and likely mediate their effects via non-bone tissues that warrant attention in future screens.

IMPROVE-BMT: A Pilot Randomized Controlled Trial of Prehabilitation Exercise for Adult Hematopoietic Stem Cell Transplant Recipients.

Background: There is limited evidence on the effects of aerobic and resistance training exercise interventions to improve physical function and patient-reported outcomes prior to autologous and allogeneic hematopoietic stem cell transplant (HSCT). IMPROVE-BMT was a single-site, pilot randomized controlled trial investigating the feasibility, acceptability, and safety of a pragmatic resistance training exercise program prior to HSCT compared to usual HSCT care. Secondary aims included differences in physical function between the exercise group (EX) and usual care control group (UC). Methods: Outcome measurements were assessed: prior to HSCT, on/around day of HSCT admission, +30 days post-HSCT, and +100 days post-HSCT. The exercise intervention was a home-based exercise program that incorporated resistance-band and bodyweight exercises. Results: Acceptability among participants was 83%; exercise adherence averaged at 92%; and there were zero exercise-related adverse or serious adverse events. The average pre-transplant exercise phase was 6.28 weeks (2.71-18.29 weeks). EX (n = 36) demonstrated larger increases in the six-minute walk test distance, short physical performance battery scores, and 30-s chair stands compared to UC (n = 38) and demonstrated significant within-group improvements for the six-minute walk test, the short physical performance battery, the 30-s chair stands, and the timed up-and-go test. Conclusions: IMPROVE-BMT demonstrates that pragmatic exercise is highly feasible for HSCT recipients and can potentially lead to enhanced recovery that may not be achievable in non-exercisers.

Relative leg-to-arm skeletal strength proportions in orangutans by species and sex.

Among extant great apes, orangutans climb most frequently. However, Bornean orangutans (Pongo pygmaeus) exhibit higher frequencies of terrestrial locomotion than do Sumatran orangutans (Pongo abelii). Variation in long bone cross-sectional geometry is known to reflect differential loading of the limbs. Thus, Bornean orangutans should show greater relative leg-to-arm strength than their Sumatran counterparts. Using skeletal specimens from museum collections, we measured two cross-sectional geometric measures of bone strength: the polar section modulus (Zpol) and the ratio of maximum to minimum area moments of inertia (Imax/Imin), at the midshaft of long bones in Bornean (n = 19) and Sumatran adult orangutans (n = 12) using medical CT and peripheral quantitative CT scans, and compared results to published data of other great apes. Relative leg-to-arm strength was quantified using ratios of femur and tibia over humerus, radius, and ulna, respectively. Differences between orangutan species and between sexes in median ratios were assessed using Wilcoxon rank sum tests. The tibia of Bornean orangutans was stronger relative to the humerus and the ulna than in Sumatran orangutans (p = 0.008 and 0.025, respectively), consistent with behavioral studies that indicate higher frequencies of terrestrial locomotion in the former. In three Zpol ratios, adult female orangutans showed greater leg-to-arm bone strength compared to flanged males, which may relate to females using their legs more during arboreal locomotion than in adult flanged males. A greater amount of habitat discontinuity on Borneo compared to Sumatra has been posited as a possible explanation for observed interspecific differences in locomotor behaviors, but recent camera trap studies has called this into question. Alternatively, greater frequencies of terrestriality in Pongo pygmaeus may be due to the absence of tigers on Borneo. The results of this study are consistent with the latter explanation given that habitat continuity was greater a century ago when our study sample was collected.

Bile salt hydrolase catalyses formation of amine-conjugated bile acids.

Bacteria in the gastrointestinal tract produce amino acid bile acid amidates that can affect host-mediated metabolic processes1-6; however, the bacterial gene(s) responsible for their production remain unknown. Herein, we report that bile salt hydrolase (BSH) possesses dual functions in bile acid metabolism. Specifically, we identified a previously unknown role for BSH as an amine N-acyltransferase that conjugates amines to bile acids, thus forming bacterial bile acid amidates (BBAAs). To characterize this amine N-acyltransferase BSH activity, we used pharmacological inhibition of BSH, heterologous expression of bsh and mutants in Escherichia coli and bsh knockout and complementation in Bacteroides fragilis to demonstrate that BSH generates BBAAs. We further show in a human infant cohort that BBAA production is positively correlated with the colonization of bsh-expressing bacteria. Lastly, we report that in cell culture models, BBAAs activate host ligand-activated transcription factors including the pregnane X receptor and the aryl hydrocarbon receptor. These findings enhance our understanding of how gut bacteria, through the promiscuous actions of BSH, have a significant role in regulating the bile acid metabolic network.

Paediatric dominant and non-dominant handgrip reference curves and the association with body composition.

BACKGROUND: Lack of paediatric reference data limits the utility of handgrip strength as a measure of fitness and well-being. AIM: To develop paediatric handgrip reference curves and evaluate associations with body size and composition and race/ethnicity group. SUBJECTS AND METHODS: Handgrip, body size and composition data were obtained from National Health and Nutrition Examination Survey 2011-2014 participants aged 6-20 years. Densitometry-derived fat and appendicular lean soft tissue mass index Z-scores (FMIZ, ALSTMIZ) were generated in participants >8 years. Dominant and non-dominant handgrip reference curves were created using the LMS method. Analyses included sample weights to produce nationally representative estimates. RESULTS: Differences in handgrip strength according to hand dominance increased with age. Handgrip strength was associated with height and arm length Z-scores (R = 0.42 to 0.47) and ALSTMIZ (R = 0.54). Handgrip strength was higher in the non-Hispanic Black group and lower in the Mexican American compared to non-Hispanic White group. Group differences were attenuated when adjusted for height, arm length or ALSTMIZ. CONCLUSION: Paediatric handgrip reference curves were generated from which individual Z-scores can be calculated separately for dominant versus non-dominant hand and adjusted for body size. Association with ALSTMIZ suggests handgrip Z-score may be used as a measure of functional body composition.

3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity.

The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome-wide association study (GWAS) efforts for childhood obesity revealed 19 independent signals for the trait; however, the mechanism of action of these loci remains to be elucidated. To molecularly characterize these childhood obesity loci we sought to determine the underlying causal variants and the corresponding effector genes within diverse cellular contexts. Integrating childhood obesity GWAS summary statistics with our existing 3D genomic datasets for 57 human cell types, consisting of high-resolution promoter-focused Capture-C/Hi-C, ATAC-seq, and RNA-seq, we applied stratified LD score regression and calculated the proportion of genome-wide SNP heritability attributable to cell type-specific features, revealing pancreatic alpha cell enrichment as the most statistically significant. Subsequent chromatin contact-based fine-mapping was carried out for genome-wide significant childhood obesity loci and their linkage disequilibrium proxies to implicate effector genes, yielded the most abundant number of candidate variants and target genes at the BDNF, ADCY3, TMEM18 and FTO loci in skeletal muscle myotubes and the pancreatic beta-cell line, EndoC-BH1. One novel implicated effector gene, ALKAL2 - an inflammation-responsive gene in nerve nociceptors - was observed at the key TMEM18 locus across multiple immune cell types. Interestingly, this observation was also supported through colocalization analysis using expression quantitative trait loci (eQTL) derived from the Genotype-Tissue Expression (GTEx) dataset, supporting an inflammatory and neurologic component to the pathogenesis of childhood obesity. Our comprehensive appraisal of 3D genomic datasets generated in a myriad of different cell types provides genomic insights into pediatric obesity pathogenesis.

Bone health in children with recurrent and chronic pancreatitis: A multi-center cross sectional analysis.

BACKGROUND/OBJECTIVES: Bone health of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) is not well studied. METHODS: This retrospective study was performed at three sites and included data from INSPPIRE-2. RESULTS: Of the 87 children in the study: 46 had ARP (53%), 41 had CP (47%). Mean age was 13.6 ± 3.9 years at last DXA scan. The prevalence of low height-for-age (Z-score < -2) (13%, 10/78) and low bone mineral density (BMD) adjusted for height (Z-score < -2) (6.4%, 5/78) were higher than a healthy reference sample (2.5%, p < 0.0001 and p = 0.03, respectively). CONCLUSION: Children with ARP or CP have lower height and BMD than healthy peers. Attention to deficits in growth and bone mineral accrual in children with pancreatic disease is warranted.

Reference ranges for body composition indices by dual energy X-ray absorptiometry from the Bone Mineral Density in Childhood Study Cohort.

BACKGROUND: Body composition assessment aids evaluation of energy stores and the impact of diseases and interventions on child growth. Current United States pediatric reference ranges from the National Health and Nutrition Examination Survey (NHANES) include 20% of children with obesity, body mass index of ≥95th percentile. OBJECTIVES: This study aimed to develop dual energy X-ray absorptiometry (DXA) based reference ranges in a diverse cohort with low-obesity prevalence from the Bone Mineral Density in Childhood Study (BMDCS). METHODS: This is a secondary analysis of a longitudinal, prospective, observational cohort. Healthy children (height and BMI within 3rd to 97th percentiles, ages 5-19 y at enrollment), from 5 United States centers were measured annually for ≤7 visits. Whole body scans were acquired using Hologic scanners. A subsample underwent repeat measurements to determine precision. We generated reference ranges for appendicular and total lean soft tissue mass index (LSTM Index), fat mass index (FMI), and other body composition measures. Resulting curves were compared to NHANES and across subgroups. Sex and age-specific equations were developed to adjust body composition Z-scores for height Z score. RESULTS: We obtained 9846 scans of 2011 participants (51% female, 22% Black, 17% Hispanic, 48% White, 7% Asian/Pacific Islander, and 6% with obesity). Precision (percent coefficient of variation) ranged from 0.7% to 1.96%. Median and-2 standard deviation curves for BMDCS and NHANES were similar, but NHANES +2 standard deviation LSTM Index and FMI curves were distinctly greater than the respective BMDCS curves. Subgroup differences were more extreme for appendicular LSTM Index-Z (mean ± SD: Asian -0.52 ± 0.93 compared with Black 0.77 ± 0.87) than for FMI-Z (Hispanic 0.29 ± 0.98 compared with Black -0.14 ± 1.1) and were smaller for Z-scores adjusted for height Z-score. CONCLUSIONS: These reference ranges add to sparse normative data regarding body composition in children and adolescents and are based on a cohort with an obesity prevalence similar to current BMI charts. Awareness of subgroup differences aids in interpreting results.

The neighborhood environment and sleep health in adolescents.

OBJECTIVE: Neighborhood-level factors, including education, health and environment, and socioeconomic exposures, are important contextual determinants of child health. We explored whether these factors, measured via the Childhood Opportunity Index 2.0, were associated with sleep health in adolescents. METHODS: Actigraphy was used to assess sleep duration, timing, and efficiency among 110 adolescents in eighth (13.9 (0.4)) and ninth (14.9 (0.4)) grade. Home addresses were geocoded and linked to Childhood Opportunity Index 2.0 scores (including 3 subtype scores and the 29 individual factor Z-scores). Mixed-effects linear regression was used to determine associations between the Childhood Opportunity Index 2.0 scores and the sleep outcomes, adjusting for sex, race, parent education, household income, school grade and weeknight status. Interactions were also tested by school grade, weeknight status, sex, and race. RESULTS: No associations were observed between overall or subtype scores with sleep outcomes in adolescents. However, we detected associations between select individual Childhood Opportunity Index 2.0 Z-scores, spanning health & environment and education domains, and sleep outcomes. For example, greater fine particulate matter was associated with later timing of sleep onset and offset; ozone concentration was associated with earlier sleep onset and offset; greater exposure to extreme temperature was associated with later sleep onset and offset and increased odds of optimal sleep efficiency. CONCLUSIONS: Specific neighborhood factors indexed by the Childhood Opportunity Index 2.0 were associated with sleep health among adolescents. In particular, neighborhood air quality measures were associated with sleep timing and efficiency, warranting further investigation.

From growth charts to growth status: how concepts of optimal growth and tempo influence the interpretation of growth measurements.

Growth measurements are largely uninterpretable without comparison to a growth chart. Consequently, the characteristics of a growth chart become an integral component of the interpretation of growth measurements. The concepts of optimal growth and tempo are well recognised by auxologists, yet their implications for interpretation of growth measurements remain problematic. This narrative review discusses the concept of optimal growth and how it serves as a guiding principle in the development and use of growth charts. The challenges of operationalising tempo for growth assessment are also discussed. Illustrative examples highlight the importance of these two central concepts in the use and interpretation of growth measurements.

Physical Activity in Youth with Down Syndrome and Its Relationship with Adiposity.

PURPOSE: The aims of this study are to (1) compare physical activity (PA) and sedentary activity (SA) in youth with and without Down syndrome (DS and non-DS) and examine the relationships of PA and SA with their traditional risk factors (age, sex, race, and body mass index Z score [BMI-Z]) and (2) explore the relationship of PA with visceral fat (VFAT) in both groups. METHODS: SenseWear accelerometry data from at least 2 weekdays and 1 weekend day were collected from youth with DS (N = 77) and non-DS (N = 57) youth. VFAT was measured by dual x-ray absorptiometry. RESULTS: In age-, sex-, race-, and BMI-Z-adjusted models, those with DS engaged in more minutes of light PA (LPA) ( p < 0.0001) and less SA ( p = 0.003) and trended toward fewer minutes of moderate-to-vigorous PA (MVPA) ( p = 0.08) than non-DS youth. No race or sex differences in MVPA were detected in those with DS, unlike non-DS. After additional adjustment for pubertal status, the relationship between MVPA and VFAT approached significance ( p = 0.06), whereas the relationships of LPA and SA with VFAT were maintained ( p ≤ 0.0001 for both). CONCLUSION: Youth with DS engage in more LPA compared with non-DS, which, in typically developing populations, can confer a more favorable weight status. Increasing the opportunity for youth with DS to engage in LPA as part of their activities of daily living may offer a viable strategy for achieving healthy weight when barriers restrict pursuit of more vigorous PA.