Increasing Equity of Physical Activity Promotion for Optimal Cardiovascular Health in Adults: A Scientific Statement From the American Heart Association.

Fewer than 1 in 4 adults achieves the recommended amount of physical activity, with lower activity levels reported among some groups. Addressing low levels of physical activity among underresourced groups provides a modifiable target with the potential to improve equity in cardiovascular health. This article (1) examines physical activity levels across strata of cardiovascular disease risk factors, individual level characteristics, and environmental factors; (2) reviews strategies for increasing physical activity in groups who are underresourced or at risk for poor cardiovascular health; and (3) provides practical suggestions for physical activity promotion to increase equity of risk reduction and to improve cardiovascular health. Physical activity levels are lower among those with elevated cardiovascular disease risk factors, among certain groups (eg, older age, female, Black race, lower socioeconomic status), and in some environments (eg, rural). There are strategies for physical activity promotion that can specifically support underresourced groups such as engaging the target community in designing and implementing interventions, developing culturally appropriate study materials, identifying culturally tailored physical activity options and leaders, building social support, and developing materials for those with low literacy. Although addressing low physical activity levels will not address the underlying structural inequities that deserve attention, promoting physical activity among adults, especially those with both low physical activity levels and poor cardiovascular health, is a promising and underused strategy to reduce cardiovascular health inequalities.

Metal Ions Can Modulate the Self-Assembly and Activity of Catalytic Peptide Amyloids.

Rational design of peptides has become a powerful tool to produce self-assembled nanostructures with the ability to catalyze different chemical reactions, paving the way to develop minimalistic enzyme-like nanomaterials. Catalytic amyloid-like assemblies have emerged among the most versatile and active, but they often require additional factors for activity. Elucidating how these factors influence the structure and activity is key for the design. Here, we showed that biologically relevant metal ions can guide and modulate the self-assembly of a small peptide into diverse amyloid architectures. The morphology and catalytic activity of the resulting fibrils were tuned by the specific metal ion decorating the surface, whereas X-ray structural analysis of the amyloids showed ion-dependent shape sizes. Molecular dynamics simulations showed that the metals can strongly affect the local conformational space, which can trigger major rearrangements of the fibrils. Our results demonstrate that the conformational landscape of catalytic amyloids is broad and tunable by external factors, which can be critical for future design strategies.

Preventing Suicide and Promoting Mental Health Among Student-Athletes From Diverse Backgrounds.

Suicide and contributing mental health conditions in athletes are shared concerns within health care and society at large. This commentary focuses on suicide risk among athletes and the role of sports medicine professionals in preventing suicide and promoting mental health. In this commentary, we draw on the scientific literature and our clinical experiences to pose and answer these questions: Does suicide risk among athletes vary by sociodemographic factors (eg, sex, gender, race/ethnicity, family income, sexual orientation) or if injured? Do sociodemographic differences influence access to and benefits from services among athletes? How do I know my athletes are at risk for suicide? What do I do if one of my athletes shares with me that they have considered suicide? Within our commentary, we review the current literature and clinical practices regarding these questions and close with actionable suggestions and recommendations for future directions.

Supporting Physical Activity in Patients and Populations During Life Events and Transitions: A Scientific Statement From the American Heart Association.

Achieving recommended levels of physical activity is important for optimal cardiovascular health and can help reduce cardiovascular disease risk. Emerging evidence suggests that physical activity fluctuates throughout the life course. Some life events and transitions are associated with reductions in physical activity and, potentially, increases in sedentary behavior. The aim of this scientific statement is to first provide an overview of the evidence suggesting changes in physical activity and sedentary behavior across life events and transitions. A second aim is to provide guidance for health care professionals or public health workers to identify changes and promote physical activity during life events and transitions. We offer a novel synthesis of existing data, including evidence suggesting that some subgroups are more likely to change physical activity behaviors in response to life events and transitions. We also review the evidence that sedentary behavior changes across life events and transitions. Tools for health care professionals to assess physical activity using simple questions or wearable devices are described. We provide strategies for health care professionals to express compassion as they ask about life transitions and initiate conversations about physical activity. Last, resources for life phase-specific, tailored physical activity support are included. Future research needs include a better characterization of physical activity and sedentary behavior across life events and transitions in higher-risk subgroups. Development and testing of interventions designed specifically to combat declines in physical activity or increases in sedentary behavior during life events and transitions is needed to establish or maintain healthy levels of these cardiovascular health-promoting behaviors.

Developmental disparities in sedentary time by period of the day among US youth: a cross-sectional study.

BACKGROUND: Definitive evidence shows sedentary time (ST) is an independent risk factor for chronic disease, irrespective of physical activity. Despite calls to limit youth ST, studies demonstrate a spike in ST at the transition from childhood to adolescence. Identifying periods of the day (e.g., before school, during school, afterschool, and evenings) during which ST is higher in adolescents vs. children-that is, specifying when within daily routines ST disparities emerge-may be important to inform intervention strategies, as periods of the day correspond with variations in setting and supervision. The purpose of this study was to examine device-assessed ST engagement by period of day and developmental stage in a nationally representative sample of United States youth. METHODS: Youth (N = 2,972 between 6-18 years) from the 2003-2004 and 2005-2006 waves of NHANES reported demographic variables and wore an accelerometer for seven consecutive days to determine ST. Linear regression analyses were applied to study associations between ST and developmental stage (childhood or adolescence) by period of the week and weekend days, while controlling for sex, race/ethnicity, annual family income, and body mass index. RESULTS: Adjusted linear regressions (p-values < 0.0001) showed that adolescents were more sedentary than children during school, afterschool, and weekday evening periods as well as all the weekend periods. However, during school (36.3 ± 7.3 vs. 28.2 ± 7.2 min/hour; b = -7.4 [-8.1, -6.6]) and afterschool periods (31.1 ± 7.7 vs. 22.7 ± 7.0 min/hour; b = -7.8 [-8.6, -7.0]) showed the largest weekly ST disparities by developmental stage. Overall, the during school and after school hours constitute most (during school = 35% and afterschool = 16%) of the weekly ST disparity between children and adolescents. CONCLUSIONS: Our data provide interventionists with estimates of the potential for ST reduction in each setting and period of the day among US adolescents. Future research should gather information about the barriers and facilitators of ST in adolescents by period of the day to help understand factors driving disparities.

Association of physical activity levels and brain white matter in older Latino adults.

OBJECTIVE: Investigate the associations between self-reported physical activity (PA) engagement and white matter (WM) health (i.e. volume, integrity, and hyperintensities) in older Latinos. DESIGN: Cross-sectional study with community-dwelling older adults from predominantly Latino neighborhoods. Participants: Thirty-four cognitively healthy older Latinos from two different cohorts. Measurements: Participants self-reported demographic information, PA engagement [Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults] and magnetic resonance imaging (MRI). We used high-resolution three-dimensional T1- and T2-FLAIR weighted images and diffusion tensor imaging acquired via 3 T MRI. We performed a series of hierarchical linear regression models with the addition of relevant covariates to examine the associations between self-reported PA levels and WM volume, integrity, and hyperintensities (separately). We adjusted p-values with the use of the Benjamini-Hochberg's false discovery rate procedure. RESULTS: Higher reported levels of leisure-time moderate-to-vigorous PA were significantly associated with higher WM volume of the posterior cingulate (ß = 0.220, SE = 0.125, 95% CI 0.009-0.431, p = 0.047) and isthmus cingulate (ß = 0.212, SE = 0.110, 95% CI 0.001-0.443, p = 0.044) after controlling for intracranial volume. Higher levels of total PA were significantly associated with higher overall WM volume of these same regions (posterior cingulate: ß = 0.220, SE = 0.125, CI 0.024-0.421, p = 0.046; isthmus cingulate: ß = 0.220, SE = 0.125, 95% CI 0.003-0.393; p = 0.040). Significant p-values did not withstand Benjamini-Hochberg's adjustment. PA was not significantly associated with WM integrity or WM hyperintensities. CONCLUSION: Higher levels of PA, particularly higher leisure-time moderate-to-vigorous PA, might be associated with greater WM volume in select white matter regions key to brain network integration for physical and cognitive functioning in older Latinos. More research is needed to further confirm these associations.

The S.P.A.C.E Hypothesis: Physical Activity as Medium - Not Medicine - for Public Health Impact.

Most scientifically tested physical activity interventions end when research funding ends; interventions that last struggle to sustain benefits. We hypothesize that long-term public health impact will benefit from a shift in how interventionists conceptualize physical activity - from a form of medicine, of value for its innate health benefits, to a malleable medium, of value for the dynamic contexts it creates.

After-School Programs and Children's Mental Health: Organizational Social Context, Program Quality, and Children's Social Behavior.

OBJECTIVE: The current study examined associations among organizational social context, after-school program (ASP) quality, and children's social behavior in a large urban park district. METHOD: Thirty-two park-based ASPs are included in the final sample, including 141 staff and 593 children. Staff reported on organizational culture (rigidity, proficiency, resistance) and climate (engagement, functionality, stress), and children's social skills and problem behaviors. Children and their parents reported on program quality indicators (e.g., activities, routines, relationships). Parents also completed a children's mental health screener. RESULTS: A series of Hierarchical Linear Models revealed that proficiency and stress were the only organizational predictors of program quality; associations between stress and program quality were moderated by program enrollment and aggregated children's mental health need. Higher child- and parent-perceived program quality related to fewer staff-reported problem behaviors, while overall higher enrollment and higher aggregated mental health need were associated with fewer staff-reported social skills. CONCLUSIONS: Data are informing ongoing efforts to improve organizational capacity of urban after-school programs to support children's positive social and behavior trajectories.

Exercise and Academic Performance Among Children With Attention-Deficit Hyperactivity Disorder and Disruptive Behavior Disorders: A Randomized Controlled Trial.

PURPOSE: To examine effects of a 10-week after-school physical activity (PA) program on academic performance of 6- to 12-year-old African American children with behavior problems. METHODS: Participants were randomized to PA (n = 19) or sedentary attention control (n = 16) programs. Academic records, curriculum-based measures, and classroom observations were obtained at baseline, postintervention, and/or follow-up. Mixed models tested group × time interactions on academic records and curriculum-based measures. One-way analysis of variance or Kruskal-Wallis tested for differences in postintervention classroom observations. RESULTS: Intent-to-treat analyses demonstrated a moderate effect within groups from baseline to postintervention on disciplinary referrals (PA: d = -0.47; attention control: d = -0.36) and a null moderate effect on academic assessments (PA: d = 0.11 to 0.36; attention control: d = 0.05 to 0.40). No significant group × time interactions emerged on direct academic assessments (all Ps ≥ .05, d = -0.23 to 0.26) or academic records (all Ps ≥ .05, d = -0.28 to 0.16). Classroom observations revealed that intervention participants were off-task due to moving at twice the rate of comparative classmates (F = 15.74, P < .001) and were off-task due to talking 33% more often (F = 1.39, P = .257). CONCLUSION: Academic outcome improvements were small within and between groups and did not sustain at follow-up. Academic benefits of after-school PA programs for children with attention-deficit hyperactivity disorder and/or disruptive behavior disorders were smaller than neurobiological, behavioral, and cognitive outcomes as previously reported.

Characterization of molecular scores and gene expression signatures in primary breast cancer, local recurrences and brain metastases.

BACKGROUND: Breast cancer is a leading cause of cancer-related death in women worldwide. Despite extensive studies in all areas of basic, clinical and applied research, accurate prognosis remains elusive, thus leading to overtreatment of many patients. Diagnosis could be improved by introducing multigene molecular scores in standard clinical practice. Several tests that work with formalin-fixed tissue have become routine. Molecular scores usually include several genes representing processes, response to oestrogens, progestogens and human epidermal growth factor receptor 2 (Her2), respectively, which are combined additively in single values. These multi-gene scores have the advantage of being more robust and reproducible than single-gene scores. Their utility may be further enhanced by combining them with classical diagnostic parameters. Here, we present an exploratory study comparing the RISK and research versions of Oncotype DX recurrence score (RS), Prosigna Risk of Recurrence (ROR) and EndoPredict (EP) with respect to their prognostic potential for ipsilateral recurrence and/or distant relapse in brain, and we compared the scores to the intrinsic subtypes based on PAM50. METHODS: RNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue cores of primary tumours, local recurrences and brain metastases. Gene expression was measured on a NanoString nCounter Analysis System. Intrinsic subtypes and molecular scores were computed according to published literature and RISK, RS, ROR and EP were compared against each other and to the intrinsic subtypes Luminal A (lumA), Luminal B (lumB), Her2-enriched (Her2↑), Basal-like (basal), and Normal-like (normal) of PAM50. Local recurrences and brain metastases were compared to their corresponding primary tumours. RESULTS: All four molecular scores were highly correlated. Highest correlations were observed among genes related to proliferation while lower correlations were found among oestrogen-related genes. The scores were significantly higher in primary tumours progressing to brain metastases as compared to recurrence-free primary tumours and primary tumours that relapsed as local recurrences. CONCLUSIONS: RISK and ROR-P are prognostic for primary tumours metastasizing to the brain. All four scores, RISK, RS, EP and ROR-P failed to discriminate between primary tumours that remained recurrence-free and primary tumours relapsing as local recurrences.

Analysis of cellular autofluorescence in touch samples by flow cytometry: implications for front end separation of trace mixture evidence.

The goal of this study was to survey optical and biochemical variation in cell populations deposited onto a surface through touch or contact and identify specific features that may be used to distinguish and then sort cell populations from separate contributors in a trace biological mixture. Although we were not able to detect meaningful biochemical variation in touch samples deposited by different contributors through preliminary antibody surveys, we did observe distinct differences in red autofluorescence emissions (650-670 nm), with as much as a tenfold difference in mean fluorescence intensities observed between certain pairs of donors. Results indicate that the level of red autofluorescence in touch samples can be influenced by a donor's contact with specific material prior to handling the substrate from which cells were collected. In particular, we observed increased red autofluorescence in cells deposited subsequent to handling laboratory gloves, plant material, and certain types of marker ink, which could be easily visualized microscopically or using flow cytometry, and persisted after hand washing. To test whether these observed optical differences could potentially be used as the basis for a cell separation workflow, a controlled two-person touch mixture was separated into two fractions via fluorescence-activated cell sorting (FACS) using gating criteria based on intensity of 650-670 nm emissions and then subjected to DNA analysis. Genetic analysis of the sorted fractions provided partial DNA profiles that were consistent with separation of individual contributors from the mixture suggesting that variation in autofluorescence signatures, even if driven by extrinsic factors, may nonetheless be a useful means of isolating contributors to some touch mixtures. Graphical Abstract Conceptual workflow diagram. Trace biological mixtures containing cells from multiple individuals are analyzed by flow cytometry. Cells are then physically separated into two populations based on intensity of red autofluorescence using Fluorescence Activated Cell Sorting. Each isolated cell fraction is subjected to DNA analysis resulting in a DNA profile for each contributor.

Biochemical Analysis of Two Single Mutants that Give Rise to a Polymorphic G6PD A-Double Mutant.

Glucose-6-phosphate dehydrogenase (G6PD) is a key regulatory enzyme that plays a crucial role in the regulation of cellular energy and redox balance. Mutations in the gene encoding G6PD cause the most common enzymopathy that drives hereditary nonspherocytic hemolytic anemia. To gain insights into the effects of mutations in G6PD enzyme efficiency, we have investigated the biochemical, kinetic, and structural changes of three clinical G6PD variants, the single mutations G6PD A+ (Asn126AspD) and G6PD Nefza (Leu323Pro), and the double mutant G6PD A- (Asn126Asp + Leu323Pro). The mutants showed lower residual activity (≤50% of WT G6PD) and displayed important kinetic changes. Although all Class III mutants were located in different regions of the three-dimensional structure of the enzyme and were not close to the active site, these mutants had a deleterious effect over catalytic activity and structural stability. The results indicated that the G6PD Nefza mutation was mainly responsible for the functional and structural alterations observed in the double mutant G6PD A-. Moreover, our study suggests that the G6PD Nefza and G6PD A- mutations affect enzyme functions in a similar fashion to those reported for Class I mutations.

Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets.

BACKGROUND: Methamphetamine (Meth) abuse is a major health problem linked to the aggravation of HIV- associated complications, especially within the Central Nervous System (CNS). Within the CNS, Meth has the ability to modify the activity/function of innate immune cells and increase brain viral loads. Here, we examined changes in the gene expression profile of neuron-free microglial cell preparations isolated from the brain of macaques infected with the Simian Immunodeficiency Virus (SIV), a model of neuroAIDS, and exposed to Meth. We aimed to identify molecular patterns triggered by Meth that could explain the detection of higher brain viral loads and the development of a pro-inflammatory CNS environment in the brain of infected drug abusers. RESULTS: We found that Meth alone has a strong effect on the transcription of genes associated with immune pathways, particularly inflammation and chemotaxis. Systems analysis led to a strong correlation between Meth exposure and enhancement of molecules associated with chemokines and chemokine receptors, especially CXCR4 and CCR5, which function as co-receptors for viral entry. The increase in CCR5 expression was confirmed in the brain in correlation with increased brain viral load. CONCLUSIONS: Meth enhances the availability of CCR5-expressing cells for SIV in the brain, in correlation with increased viral load. This suggests that Meth is an important factor in the susceptibility to the infection and to the aggravated CNS inflammatory pathology associated with SIV in macaques and HIV in humans.

Functional and Biochemical Characterization of Three Recombinant Human Glucose-6-Phosphate Dehydrogenase Mutants: Zacatecas, Vanua-Lava and Viangchan.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency in humans causes severe disease, varying from mostly asymptomatic individuals to patients showing neonatal jaundice, acute hemolysis episodes or chronic nonspherocytic hemolytic anemia. In order to understand the effect of the mutations in G6PD gene function and its relation with G6PD deficiency severity, we report the construction, cloning and expression as well as the detailed kinetic and stability characterization of three purified clinical variants of G6PD that present in the Mexican population: G6PD Zacatecas (Class I), Vanua-Lava (Class II) and Viangchan (Class II). For all the G6PD mutants, we obtained low purification yield and altered kinetic parameters compared with Wild Type (WT). Our results show that the mutations, regardless of the distance from the active site where they are located, affect the catalytic properties and structural parameters and that these changes could be associated with the clinical presentation of the deficiency. Specifically, the structural characterization of the G6PD Zacatecas mutant suggests that the R257L mutation have a strong effect on the global stability of G6PD favoring an unstable active site. Using computational analysis, we offer a molecular explanation of the effects of these mutations on the active site.

Glucose-6-Phosphate Dehydrogenase: Update and Analysis of New Mutations around the World.

Glucose-6-phosphate dehydrogenase (G6PD) is a key regulatory enzyme in the pentose phosphate pathway which produces nicotinamide adenine dinucleotide phosphate (NADPH) to maintain an adequate reducing environment in the cells and is especially important in red blood cells (RBC). Given its central role in the regulation of redox state, it is understandable that mutations in the gene encoding G6PD can cause deficiency of the protein activity leading to clinical manifestations such as neonatal jaundice and acute hemolytic anemia. Recently, an extensive review has been published about variants in the g6pd gene; recognizing 186 mutations. In this work, we review the state of the art in G6PD deficiency, describing 217 mutations in the g6pd gene; we also compile information about 31 new mutations, 16 that were not recognized and 15 more that have recently been reported. In order to get a better picture of the effects of new described mutations in g6pd gene, we locate the point mutations in the solved three-dimensional structure of the human G6PD protein. We found that class I mutations have the most deleterious effects on the structure and stability of the protein.

Clinical Significance of Nonsustained Ventricular Tachycardia on Routine Monitoring of Pacemaker Patients.

BACKGROUND: Permanent pacemakers (PPMs) are capable of recording tachyarrhythmic events including nonsustained ventricular tachycardia (NSVT), though the clinical significance of NSVT on routine PPM evaluation is unknown. Our goals: assess the prevalence of NSVT on routine PPM follow-up and survival of PPM patients with NSVT, without NSVT, and with ventricular high rate (VHR) episodes of undefined origin. METHODS: A single-center retrospective, cohort study was performed on patients implanted with PPMs capable of recording NSVT, defined as ≥5 consecutive ventricular beats at ≥170/minutes lasting <30 seconds. Patients were categorized: (1) no NSVT; (2) NSVT; or (3) VHR episodes of uncertain etiology. The primary endpoint was all-cause mortality within 6 months of last follow-up. RESULTS: Note that in 1,125 enrollees (51.8% male, age 74.2 ± 15.5 years, ejection fraction 57.0 ± 9.0%), 742 (66%) had no NSVT, 223 had NSVT (20%), and 160 (14%) had VHR. There were no differences in ejection fraction, diabetes, hypertension, coronary disease, prior myocardial infarction, baseline creatinine, QRS duration, prevalence of left bundle branch block, or ß-blocker use among groups. "No NSVT" patients were older (P = 0.013), NSVT patients had more males (P = 0.012); atrial fibrillation and digoxin use were more prevalent in VHR patients (P < 0.01). During median follow-up of 2.8 years there were 93 deaths within 6 months of last follow-up with no differences in survival among groups (log rank P = 0.47). Age, ejection fraction at time of implant, and ß-blocker use were independent predictors of survival. CONCLUSION: NSVT detected on routine PPM follow-up in this patient population with a preserved ejection fraction is not associated with long-term mortality.

Independent Associations of Organized Physical Activity and Weight Status with Children's Cognitive Functioning: A Matched-Pairs Design.

PURPOSE: This study tested whether participation in organized physical activity (active vs. inactive) or weight status (normal weight vs. overweight or obese) independently relate to children's cognition, using a matched-pairs design. DESIGN AND METHODS: Normal weight, active children (8-11 yrs, 5th-75th percentile BMI) were recruited from extracurricular physical activity programs while normal weight inactive (5th-75th percentile BMI) and overweight inactive children (BMI ≥85th percentile) were recruited from local Augusta, Georgia area schools. Measures included the Cognitive Assessment System, anthropometrics, and parent- and self-report of physical activity. Paired t tests compared cognition scores between matched groups of normal weight active vs. normal weight inactive (N = 24 pairs), normal weight inactive vs. overweight inactive (N = 21 pairs), and normal weight active vs. overweight inactive children (N = 16 pairs). Children in each comparison were matched for race, gender, age, and socioeconomic status. RESULTS: Normal weight active children had higher Planning (M± SD = 109 ± 11 vs. 100 ± 11, p = .011) and Attention scores (108 ± 11 vs. 100 ± 11, p = .013) than overweight inactive children. Normal weight inactive children had higher Attention scores than overweight inactive children (105 ± 13 vs. 93 ± 12, p = .008). When compared with normal weight inactive children, normal weight active children had higher Planning (113 ± 10 vs. 102 ± 13, p = .008) and marginally higher Attention scores (111 ± 11 vs. 104 ± 12, p = .06). CONCLUSION: Findings suggest independent associations of children's weight status with selective attention, and physical activity with higher-order processes of executive function.

Mutations of Glucose-6-Phosphate Dehydrogenase Durham, Santa-Maria and A+ Variants Are Associated with Loss Functional and Structural Stability of the Protein.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in the world. More than 160 mutations causing the disease have been identified, but only 10% of these variants have been studied at biochemical and biophysical levels. In this study we report on the functional and structural characterization of three naturally occurring variants corresponding to different classes of disease severity: Class I G6PD Durham, Class II G6PD Santa Maria, and Class III G6PD A+. The results showed that the G6PD Durham (severe deficiency), and the G6PD Santa Maria and A+ (less severe deficiency) (Class I, II and III, respectively) affect the catalytic efficiency of these enzymes, are more sensitive to temperature denaturing, and affect the stability of the overall protein when compared to the wild type WT-G6PD. In the variants, the exposure of more and buried hydrophobic pockets was induced and monitored with 8-Anilinonaphthalene-1-sulfonic acid (ANS) fluorescence, directly affecting the compaction of structure at different levels and probably reducing the stability of the protein. The degree of functional and structural perturbation by each variant correlates with the clinical severity reported in different patients.

Diagnostic exome sequencing to elucidate the genetic basis of likely recessive disorders in consanguineous families.

Rare, atypical, and undiagnosed autosomal-recessive disorders frequently occur in the offspring of consanguineous couples. Current routine diagnostic genetic tests fail to establish a diagnosis in many cases. We employed exome sequencing to identify the underlying molecular defects in patients with unresolved but putatively autosomal-recessive disorders in consanguineous families and postulated that the pathogenic variants would reside within homozygous regions. Fifty consanguineous families participated in the study, with a wide spectrum of clinical phenotypes suggestive of autosomal-recessive inheritance, but with no definitive molecular diagnosis. DNA samples from the patient(s), unaffected sibling(s), and the parents were genotyped with a 720K SNP array. Exome sequencing and array CGH (comparative genomic hybridization) were then performed on one affected individual per family. High-confidence pathogenic variants were found in homozygosity in known disease-causing genes in 18 families (36%) (one by array CGH and 17 by exome sequencing), accounting for the clinical phenotype in whole or in part. In the remainder of the families, no causative variant in a known pathogenic gene was identified. Our study shows that exome sequencing, in addition to being a powerful diagnostic tool, promises to rapidly expand our knowledge of rare genetic Mendelian disorders and can be used to establish more detailed causative links between mutant genotypes and clinical phenotypes.

Sociodemographic disparities in sedentary time among US youth vary by period of the day.

INTRODUCTION: Studies have reported sex and race/ethnicity disparities in sedentary time (ST), but none have evaluated ST by well-defined periods of the weekday (before school, during school, afterschool, and evening) and weekend day (morning, afternoon, and evening). Comparing sex and race/ethnicity disparities in ST at different periods of a weekday and weekend day can deepen our understanding of disparities and inform intervention efforts. This study tests sex and race/ethnicity disparities in ST by period of day in a representative sample of US youth. METHODS: Youth (N = 2,972) from the 2003-2006 NHANES waves reported demographic variables and wore an accelerometer for 7 consecutive days to assess ST. Linear regressions were conducted to test relationships between sex and race/ethnicity and ST (min/hour) during each period of a weekday and weekend day. ST differences by sex and race/ethnicity were calculated to identify the periods of the day presenting the largest opportunity to reduce disparities. RESULTS: Females were more sedentary than males during school (p < 0∙0001), afterschool (p < 0∙0001), and weekday evenings (p < 0∙0001) after controlling for covariates. After controlling for covariates, race/ethnicity only was a significant predictor of ST during weekend mornings (p < 0∙0001). During school and afterschool emerged as the periods with the largest opportunities to reduce sex disparities in ST. Weekend mornings were identified as the largest opportunity to reduce race/ethnic disparities in ST. CONCLUSIONS: Sex disparities in ST appear to be driven mostly by the during school period of the day, while race/ethnic disparities in ST seem to be driven by the weekend morning period. Future intervention work should consider these periods when aiming to reduce ST disparities in youth.