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Physiological response to physical exercise through analysis of cardiopulmonary measurements has been shown to be predictive of a variety of diseases. Nonetheless, the clinical use of exercise testing remains limited because interpretation of test results requires experience and specialized training. Additionally, until this work no methods have identified which dynamic gas exchange or heart rate responses influence an individual's decision to start or stop physical activity. This research examines the use of advanced machine learning methods to predict completion of a test consisting of multiple exercise bouts by a group of healthy children and adolescents. All participants could complete the ten bouts at low or moderate-intensity work rates, however, when the bout work rates were high-intensity, 50% refused to begin the subsequent exercise bout before all ten bouts had been completed (task failure). We explored machine learning strategies to model the relationship between the physiological time series, the participant's anthropometric variables, and the binary outcome variable indicating whether the participant completed the test. The best performing model, a generalized spectral additive model with functional and scalar covariates, achieved 93.6% classification accuracy and an F1 score of 93.5%. Additionally, functional analysis of variance testing showed that participants in the 'failed' and 'success' groups have significantly different functional means in three signals: heart rate, oxygen uptake rate, and carbon dioxide uptake rate. Overall, these results show the capability of functional data analysis with generalized spectral additive models to identify key differences in the exercise-induced responses of participants in multiple bout exercise testing.

Spanish Ministry of Economy and Competitiveness, Grant/Award Number: DEP2013--47540, DEP2016-79512--R and DEP2017--91544--EXP; Spanish Ministry of Economy, Industry and Competitiveness (MINECO); European Regional Development Fund (FEDER), Grant/Award Number: RYC--2016--21199 and ENDORE SAF2017--87526--R; Junta de Andalucia, Grant/Award Number: BIO--302 and US--1254251; University of Jaen, Grant/Award Number: PAIUJA--EI_CTS02; Spanish Ministry of Education, Culture and Sport, Grant/Award Number: FPU 16/02760; NIH, Grant/Award Number:UO1 TR002004; PERC Systems Biology Fund; Unit of Excellence on EXERNET Research Network on Exercise and Health in Special Populations; Alicia Koplowitz Foundation; Henning Och Johan Throne--Holsts Stiftelse Grant; University of Granada, Plan Propio de Investigacion 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES); Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades and European Regional Development Fund (ERDF), Grant/Award Number: SOMM17/6107/UGR; European Regional Development Funds, Grant/Award Number: B--CTS-355--UGR18 and B--CTS--500--UGR18; Funding for open access charge: Universidad de Granada/CBUA, Objectives: High cardiorespiratory fitness (CRF) levels reduce the risk of developing cardiovascular disease (CVD) during adulthood. However, little is known about the molecular mechanisms underlying the health benefits of high CRF levels at the early stage of life. This study aimed to analyze the whole-blood transcriptome profile of fit children with overweight/obesity (OW/OB) compared to unfit children with OW/OB. Design: 27 children with OW/OB (10.14 ± 1.3 years, 59% boys) from the ActiveBrains project were evaluated. VO2peak was assessed using a gas analyzer, and participants were categorized into fit or unfit according to the CVD risk-related cut-points. Whole-blood transcriptome profile (RNA sequencing) was analyzed. Differential gene expression analysis was performed using the limma R/Bioconductor software package (analyses adjusted by sex and maturational status), and pathways’ enrichment analysis was performed with DAVID. In addition, in silico validation data mining was performed using the PHENOPEDIA database. Results: 256 genes were differentially expressed in fit children with OW/OB compared to unfit children with OW/OB after adjusting by sex and maturational status (FDR < 0.05). Enriched pathway analysis identified gene pathways related to inflammation (eg, dopaminergic and GABAergic synapse pathways). Interestingly, in silico validation data mining detected a set of the differentially expressed genes to be related to CVD, metabolic syndrome, hypertension, inflammation, and asthma. Conclusion: The distinct pattern of whole-blood gene expression in fit children with OW/OB reveals genes and gene pathways that might play a role in reducing CVD risk factors later in life., Spanish Ministry of Economy and Competitiveness DEP2013-47540 DEP2016-79512-R DEP2017-91544-EXP, Spanish Ministry of Economy, Industry and Competitiveness (MINECO), European Commission RYC-2016-21199, ENDORE SAF2017-87526-R, Junta de Andalucia BIO-302 US-1254251, University of Jaen PAIUJA-EI_CTS02, Spanish Ministry of Education, Culture and Sport FPU 16/02760, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA UO1 TR002004, PERC Systems Biology Fund, Unit of Excellence on EXERNET Research Network on Exercise and Health in Special Populations, Alicia Koplowitz Foundation, Henning Och Johan Throne-Holsts Stiftelse Grant, University of Granada, Unit of Excellence on Exercise and Health (UCEES), Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades and European Regional, Development Fund (ERDF) SOMM17/6107/UGR European Commission B-CTS-355-UGR18 B-CTS-500-UGR18, Universidad de Granada/CBUA

Physiological response to physical exercise through analysis of cardiopulmonary measurements has been shown to be predictive of a variety of diseases. Nonetheless, the clinical use of exercise testing remains limited because interpretation of test results requires experience and specialized training. Additionally, until this work no methods have identified which dynamic gas exchange or heart rate responses influence an individual’s decision to start or stop physical activity. This research examines the use of advanced machine learning methods to predict completion of a test consisting of multiple exercise bouts by a group of healthy children and adolescents. All participants could complete the ten bouts at low or moderate-intensity work rates, however, when the bout work rates were high-intensity, 50% refused to begin the subsequent exercise bout before all ten bouts had been completed (task failure). We explored machine learning strategies to model the relationship between the physiological time series, the participant’s demographic variables, and the binary outcome variable indicating whether the participant completed the test. The best performing model, a generalized spectral additive model with functional and scalar covariates, achieved 93.6% classification accuracy and an F1 score of 93.5%. Additionally, functional analysis of variance testing showed that participants in the ’failed’ and ’success’ groups have significantly different functional means in three signals: heart rate, oxygen uptake rate, and carbon dioxide uptake rate. Overall, these results show the capability of functional data analysis with generalized spectral additive models to identify key differences in the exercise-induced responses of participants in multiple bout exercise testing.

SignificanceGrowing levels of obesity and metabolic syndrome have driven demand for more advanced forms of body composition assessment. While various techniques exist to measure body composition, devices are typically expensive and not portable, involve radiation [in the case of dual-energy x-ray absorptiometry (DXA)], and are limited to analysis of adiposity while metabolic information from blood supply and oxygenation are not considered.AimWe evaluate whether diffuse optical spectroscopic imaging (DOSI) can be used to predict site-specific adiposity and percent fat (whole body) while simultaneously providing information about local tissue hemoglobin levels and oxygenation.ApproachDOSI measures of tissue composition in gastrocnemius, quadriceps, abdomen, and biceps, DXA whole-body composition, and ultrasound-derived skin and adipose tissue thickness (SATT) in the quadriceps were obtained from 99 individuals aged 7 to 34 years old.ResultsVarious DOSI-derived parameters were correlated with SATT and an optical method is proposed for estimating SATT using a newly defined parameter, the optical fat fraction (OFF), which considers all parameters that correlate with SATT. Broadband absorption and scattering spectra from study participants with the thinnest (SATT ≈ 0.25 ± 0.02 cm) and thickest SATT (SATT ≈ 1.55 ± 0.14 cm), representing best estimates for pure in vivo lean and fatty tissue, respectively, are reported. Finally, a trained prediction model is developed which allows DOSI assessment of OFF to predict DXA body-fat percentage, demonstrating that DOSI can be used to quantify body composition.ConclusionsThis study shows that DOSI can be used to assess the adiposity of specific tissues or the entire human body, and the OFF parameter is defined for corroboration and further evaluation in future research.

Background Youth populations with overweight/obesity (OW/OB) exhibit heterogeneity in cardiometabolic health phenotypes. The underlying mechanisms for those differences are still unclear. This study aimed to analyze the whole-blood transcriptome profile (RNA-seq) of children with metabolic healthy overweight/obesity (MHO) and metabolic unhealthy overweight/obesity (MUO) phenotypes. Methods Twenty-seven children with OW/OB (10.1 ± 1.3 years, 59% boys) from the ActiveBrains project were included. MHO was defined as having none of the following criteria for metabolic syndrome: elevated fasting glucose, high serum triglycerides, low high-density lipoprotein-cholesterol, and high systolic or diastolic blood pressure, while MUO was defined as presenting one or more of these criteria. Inflammatory markers were additionally determined. Total blood RNA was analyzed by 5'-end RNA-sequencing. Results Whole-blood transcriptome analysis revealed a distinct pattern of gene expression in children with MHO compared to MUO children. Thirty-two genes differentially expressed were linked to metabolism, mitochondrial, and immune functions. Conclusions The identified gene expression patterns related to metabolism, mitochondrial, and immune functions contribute to a better understanding of why a subset of the population remains metabolically healthy despite having overweight/obesity. Impact A distinct pattern of whole-blood transcriptome profile (RNA-seq) was identified in children with metabolic healthy overweight/obesity (MHO) compared to metabolic unhealthy overweight/obesity (MUO) phenotype. The most relevant genes in understanding the molecular basis underlying the MHO/MUO phenotypes in children could be: RREB1, FAM83E, SLC44A1, NRG1, TMC5, CYP3A5, TRIM11, and ADAMTSL2. The identified whole-blood transcriptome profile related to metabolism, mitochondrial, and immune functions contribute to a better understanding of why a subset of the population remains metabolically healthy despite having overweight/obesity.

PurposeThe electronic health record, data science advances, and dynamic environmental and infectious threats to child health highlight the need for harmonized and interoperable approaches to pediatric cardiopulmonary exercise testing (CPET). Accordingly, we developed a terminology harmonization in exercise medicine and exercise science domain analysis model (THEMES DAM) to structure CPET data elements.MethodsTHEMES DAM identified 114 data elements, including participant information, calibration, equipment, protocols, laboratory personnel, encouragement strategies, and analysis procedures. We used the THEMES DAM, vetted by the international data standards organization HL7, to construct a current-state survey of pediatric CPET centers in the United States. Forty-eight of 101 centers responded to a questionnaire covering seven major topic areas (38 items).ResultsCenters predominantly performed between 100 and 500 tests annually. Cardiac disease represented 55% of referrals. Almost all centers calibrated gas concentrations and flow daily, but 42% never calibrated their treadmill or cycle ergometers. All centers measured V̇O2peakbut calculated differently. Centers used a variety of protocols (e.g., for treadmill: 61%, Bruce; 43%, modified Bruce; 59%, other); 44% calculated CPET slopes from submaximal portions of CPET (e.g., V̇O2-HR). All centers verbally encouraged participants, but only 40% used a standardized approach. The interpretation of CPET was done by physicians (60%), exercise physiologists (25%), exercise technicians (10%), nurses (1%), or others (4%). Ninety-one percent would agree to collaborate in multicenter research, 89% to establish dynamic reference values, and 83% to better interpret CPET.ConclusionsThe survey data and the implementation of THEMES DAM could accelerate interoperability across multiple centers. This would facilitate a nimble approach to create pediatric reference values responsive to the constantly changing health environment and stimulate novel approaches to CPET research and clinical application.

Objective Patients show substantial differences in response to rehabilitation therapy after stroke. We hypothesized that specific genetic profiles might explain some of this variance and, secondarily, that genetic factors are related to cerebral atrophy post-stroke. Methods The phase 3 ICARE study examined response to motor rehabilitation therapies. In 216 ICARE enrollees, DNA was analyzed for presence of the BDNF val66met and the ApoE ε4 polymorphism. The relationship of polymorphism status to 12-month change in motor status (Wolf Motor Function Test, WMFT) was examined. Neuroimaging data were also evaluated (n=127). Results Subjects were 61±13 years old (mean±SD) and enrolled 43±22 days post-stroke; 19.7% were BDNF val66met carriers and 29.8% ApoE ε4 carriers. Carrier status for each polymorphism was not associated with WMFT, either at baseline or over 12 months of follow-up. Neuroimaging, acquired 5±11 days post-stroke, showed that BDNF val66met polymorphism carriers had a 1.34-greater degree of cerebral atrophy compared to non-carriers (P=.01). Post hoc analysis found that age of stroke onset was 4.6 years younger in subjects with the ApoE ε4 polymorphism (P=.02). Conclusion Neither the val66met BDNF nor ApoE ε4 polymorphism explained inter-subject differences in response to rehabilitation therapy. The BDNF val66met polymorphism was associated with cerebral atrophy at baseline, echoing findings in healthy subjects, and suggesting an endophenotype. The ApoE ε4 polymorphism was associated with younger age at stroke onset, echoing findings in Alzheimer’s disease and suggesting a common biology. Genetic associations provide insights useful to understanding the biology of outcomes after stroke.

BackgroundIncreased physical activity (PA) may protect against asthma but PA can trigger asthma symptoms.ObjectiveTo investigate relationships between moderate-to-vigorous PA (MVPA) assessed during routine care visits and incident asthma.MethodsFor this retrospective cohort, 542,486 children between 2 and 17 years from 2010 to 2017 were included who had an MVPA assessment (exercise vital sign) during routine care visits. The association of MVPA and asthma was analyzed using Cox proportional hazards regression models as a function of age, with MVPA and body mass index (BMI) being time-varying factors, adjusted for race and ethnicity, socioeconomic status, and air pollution.ResultsThe mean MVPA was 5.4 (standard deviation: 4.4) hours/week. Crude asthma incidence density rate (IDR) was highest in children with

INTRODUCTION: Physical activity and fitness are essential for healthy growth in children. The National Health and Nutrition Examination Survey (NHANES) evaluated fitness by estimating [Formula: see text] max from submaximal measurements of heart rate (HR) during graded treadmill exercise. Our aims were (a) to examine how well NHANES methodology used to estimate [Formula: see text] max correlated with actual VO(2)max and (b) to evaluate a novel fitness metric using actual data collected during exercise and its relationship to physical activity and sedentary time, lipid profiles, and body composition. METHODS: Fifty-three adolescents completed NHANES submaximal exercise protocol and maximal graded cardiopulmonary exercise testing. We used a novel approach to quantifying fitness (Δvelocity × incline × body mass (VIM)/ΔHR slopes) and evaluated its relationship to physical activity and sedentary time using NHANES data (n = 4498). In a subset (n = 740), we compared ΔVIM/ΔHR slopes to NHANES estimated [Formula: see text] max and examined their relationship to cardiovascular risk factors (BMI percentiles and lipid levels). RESULTS: Measured [Formula: see text] peak was moderately correlated with NHANES estimated [Formula: see text] max (r = 0.53, P < 0.01). Significantly higher ΔVIM/ΔHR slopes were associated with increased physical activity and decreased sedentary time. ΔVIM/ΔHR slopes were negatively associated with LDL, triglycerides, and BMI percentiles (P < 0.01). In general, the two fitness models were similar; however, ΔVIM/ΔHR was more discriminating than NHANES in quantifying the relationship between fitness and LDL levels. CONCLUSION: We found that the NHANES estimated [Formula: see text] max accounted for approximately 28% of the variability in the measured [Formula: see text] peak. Our approach to estimating fitness (ΔVIM/ΔHR slopes) using actual data provided similar relationships to lipid levels. We suggest that fitness measurements based on actually measured data may produce more accurate assessments of fitness and, ultimately, better approaches linking exercise to health in children.

Pompe disease is a progressive myopathy resulting from deficiency in lysosomal enzyme acid α-glucosidase (GAA), which leads to glycogen accumulation in lysosomes primarily in skeletal and cardiac muscle. Enzyme replacement therapy (ERT) with recombinant human (rh) GAA works well in alleviating the cardiomyopathy; however, many patients continue to have progressive muscle weakness. The purpose of this study was to evaluate the effectiveness of a respiratory training combined with 24-week supervised resistance training program on muscle strength (measured by Biodex)), and respiratory function including maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP) in subjects with late onset Pompe disease receiving ERT. Ten subjects participated in a 24-week resistance exercise program, three times per week, in addition to respiratory muscle exercise training six days per week. Overall, at the end of the resistance training program, as measured by Biodex dynamometry, the leg extensor strength improved by 10.5 ± 3.2Nm. (p 0.01), leg flexors improved by 12.1 ± 4.1Nm (p 0.01), the elbow flexors improved by 5.1 ± 2.3Nm (p = 0.03), and the elbow extensor strength improved by a mean of 4.5 ± 1.9Nm. (p = 0.02). MIP improved by 8.5 ± 3.7 cm H

ObjectiveWe evaluated the safety of maximal cardiopulmonary exercise testing (CPET) in individuals with sickle cell disease (SCD). Maximal CPET using gas exchange analysis is the gold standard for measuring cardiopulmonary fitness in the laboratory, yet its safety in the SCD population is unclear.DesignSystematic review.Data sourcesSystematic search of Medline (PubMed), EMBASE, Cochrane, ClinicalTrials.gov and professional society websites for all published studies and abstracts through December 2020.Eligibility criteria for selecting studiesTwo reviewers independently extracted data of interest from studies that assessed safety outcomes of maximal CPET in children and adults with SCD. A modified version of the Newcastle-Ottawa Scale was used to assess for risk of bias in studies included.ResultsIn total, 24 studies met inclusion/exclusion criteria. Adverse events were reported separately or as part of study results in 36 (3.8%) of 939 participants with SCD undergoing maximal CPET in studies included. Most adverse events were related to transient ischaemic changes on ECG monitoring or oxygen desaturation during testing, which did not result in arrhythmias or other complications. Only 4 (0.43%) of 939 participants experienced pain events due to maximal CPET.ConclusionMaximal CPET appears to be a safe testing modality in children and adults with SCD and can be used to better understand the physiological basis of reduced exercise capacity and guide exercise prescription in this population. Some studies did not focus on reporting adverse events related to exercise testing or failed to mention safety monitoring, which contributed to risk of bias.

We explored the incidence of acute mountain sickness (AMS) and extravascular lung water (ELW) in children in relation to changes in body composition and peripheral blood oxygenation (SIn a prospective cohort study, 10 children (7 female, ages 7-14 y) and 10 sex-matched adults (ages 23-44 y) traveled via automobile from sea level to 3000 m for 2 nights, followed by 4 nights at 3800 m. Each morning, body mass and body water (bioelectrical impedance), SNo differences were found between children and adults in SChildren demonstrated a higher incidence of AMS than adults, with greater severity among those AMS+. The loss of body water and body mass at high altitude was also greater in children, albeit unrelated to AMS severity. In addition to awareness of AMS, strategies to maintain body weight and hydration in children traveling to high altitudes should be considered.

Background Understanding SARS-CoV-2 infection in children is necessary to reopen schools safely. Methods We measured SARS-CoV-2 infection in 320 learners [10.5 ± 2.1 (sd); 7–17 y.o.] at four diverse schools with either remote or on-site learning. Schools A and B served low-income Hispanic learners; school C served many special-needs learners, and all provided predominantly remote instruction. School D served middle- and upper-income learners, with predominantly on-site instruction. Testing occurred in the fall (2020), and 6–8 weeks later during the fall-winter surge (notable for a tenfold increase in COVID-19 cases). Immune responses and mitigation fidelity were also measured. Results We found SARS-CoV-2 infections in 17 learners only during the surge. School A (97% remote learners) had the highest infection (10/70, 14.3%, p Conclusions Schools can implement successful mitigation strategies across a wide range of student diversity. Despite asymptomatic to mild SARS-CoV-2 infection, children generate robust humoral and cellular immune responses. Impact Successful COVID-19 mitigation was implemented across a diverse range of schools. School-associated SARS-CoV-2 infections reflect regional rates rather than remote or on-site learning. Seropositive school-aged children with asymptomatic to mild SARS-CoV-2 infections generate robust humoral and cellular immunity.

Study Objectives Aerobic fitness (AF) and sleep are major determinants of health in adolescents and impact neurocognitive and psychological development. However, little is known about the interactions between AF and sleep during the developmental transition experienced across adolescence. This study aimed to consider the relationships between AF and habitual sleep patterns and sleep neurophysiology in healthy adolescents. Methods Subjects (mean age = 14.6 ± 2.3 years old, range 11–17, 11 females) were evaluated for AF (peak VO2 assessed by ramp-type progressive cycle ergometry in the laboratory), habitual sleep duration and efficiency (7–14 days actigraphy), and topographic patterns of spectral power in slow wave, theta, and sleep spindle frequencies in non-rapid eye movement (NREM) sleep using overnight polysomnography (PSG) with high-density electroencephalography (hdEEG, 128 channels). Results Significant relationships were observed between peak VO2 and habitual bedtime (r = −0.650, p = .009) and wake-up time (r = −0.603, p = .017), with greater fitness associated with going to bed and waking up earlier. Peak VO2 significantly predicted slow oscillations (0.5–1 Hz, p = .018) and theta activity (4.5–7.5 Hz, p = .002) over anterior frontal and central derivations (p < .001 and p = .001, respectively) after adjusting for sex and pubertal development stage. Similar associations were detected for fast sleep spindle activity (13–16 Hz, p = .006), which was greater over temporo-parietal derivations. Conclusions Greater AF was associated with a more mature pattern of topographically-specific features of sleep EEG known to support neuroplasticity and cognitive processes and which are dependent on prefrontal cortex and hippocampal function in adolescents and adults. AF was also correlated with a smaller behavioral sleep phase delay commonly seen during adolescence.

Introduction: During the COVID-19 pandemic, some K-12 schools resumed in-person classes with varying degrees of mitigation plans in the fall of 2020. Physical distancing and face coverings can minimize SARS-CoV-2 spread, the virus that causes COVID-19. However, no research has focused on mitigation strategy adherence during school days. Thus, we sought to develop a systematic observation protocol to capture COVID-19 mitigation strategy adherence in school environments: The Systematic Observation of COVID-19 Mitigation (SOCOM). Methods: We extended previously validated and internationally used tools to develop the SOCOM training and implementation protocol to assess physical distancing and face covering behaviors. SOCOM was tested in diverse indoor and outdoor settings (classrooms, lunchrooms, physical education [PE], and recess) among diverse schools (elementary, secondary, and special needs). Results: For the unique metrics of physical-distancing and face-covering behaviors, areas with more activity and a maximum of 10-15 students were ideal for accurately capturing data. Overall proportion of agreement was high for physical distancing (90.9%), face covering (88.6%), activity type (89.2%), and physical activity level (87.9%). Agreement was lowest during active recess, PE, and observation areas with ≥20 students. Conclusions: Millions of children throughout the US are likely to return to school in the months ahead despite the current surge of COVID-19 cases. SOCOM is a relatively inexpensive tool that can be implemented by schools to determine mitigation strategy adherence and assess changes to protocols to help students return to school safely and slow the spread of COVID-19 and can be used for research purposes.

Recreational cycling is a popular activity which stimulates and improves cardiovascular fitness. The corresponding benefits for bone are unclear. This study examined the effect of running (high-impact) vs. cycling (low-impact), at the same moderate-to-vigorous exercise intensity, on markers of bone formation (N-terminal propeptide of type I collagen, PINP) and bone resorption (C-telopeptide of type I collagen, CTX-1), a non-collagenous bone remodeling marker (osteocalcin), as well as bone-modulating factors, including parathyroid hormone (PTH), irisin (myokine) and sclerostin (osteokine). Thirteen healthy men (23.7 ± 1.0 y) performed two progressive exercise tests to exhaustion (peak VO2) on a cycle ergometer (CE) and on a treadmill (TM). On subsequent separate days, in randomized order, participants performed 30-min continuous running or cycling at 70% heart rate reserve (HRR). Blood was drawn before, immediately post- and 1 h into recovery. PTH transiently increased (CE, 51.7%; TM, 50.6%) immediately after exercise in both exercise modes. Sclerostin levels increased following running only (27.7%). Irisin increased following both running and cycling. In both exercise modes, CTX-1 decreased immediately after exercise, with no significant change in PINP and osteocalcin. At the same moderate-to-vigorous exercise intensity, running appears to result in a greater transient sclerostin response compared with cycling, while the responses of bone markers, PTH and irisin are similar. The longer-term implications of this differential bone response need to be further examined.

Recreational cycling is a popular activity which stimulates and improves cardiovascular fitness. The corresponding benefits for bone are unclear. This study examined the effect of running (high-impact) vs. cycling (low-impact), at the same moderate-to-vigorous exercise intensity, on markers of bone formation (N-terminal propeptide of type I collagen, PINP) and bone resorption (C-telopeptide of type I collagen, CTX-1), a non-collagenous bone remodeling marker (osteocalcin), as well as bone-modulating factors, including parathyroid hormone (PTH), irisin (myokine) and sclerostin (osteokine). Thirteen healthy men (23.7±1.0 y) performed two progressive exercise tests to exhaustion (peak VO2) on a cycle ergometer (CE) and on a treadmill (TM). On subsequent separate days, in randomized order, participants performed 30-min continuous running or cycling at 70% heart rate reserve (HRR). Blood was drawn before, immediately post- and 1h into recovery. PTH transiently increased (CE, 51.7%; TM, 50.6%) immediately after exercise in both exercise modes. Sclerostin levels increased following running only (27.7%). Irisin increased following both running and cycling. In both exercise-modes, CTX-1 decreased immediately after exercise, with no significant change in PINP and osteocalcin. At the same moderate-to-vigorous exercise intensity, running appears to result in a greater transient sclerostin response compared with cycling, while the responses of bone markers, PTH and irisin are similar. The longer-term implications of this differential bone response need to be further examined.

Cold water immersion (CWI) purportedly reduces inflammation and improves muscle recovery post exercise, yet its effectiveness in specific contexts (ultraendurance) remains unclear. Thus, our aim was to study hematological profiles, systemic inflammation, and muscle damage responses to a specific post race CWI (vs. control) during recovery after the Ironman® World Championship, a culmination of ~100,000 athletes competing in global qualifying Ironman® events each year. Twenty-nine competitors were randomized into CWI or control (CON) group. Physiological parameters and blood samples were taken pre race (BASE), after intervention (POST), and 24 (+1DAY) and 48 hours (+2DAY) following the race. Muscle damage markers (plasma myoglobin, serum creatine kinase) were elevated at POST, +1DAY, and +2DAY, while inflammatory cytokines IL-6, IL-8, and IL-10 and total leukocyte counts were increased only at POST. CWI had no effect on these markers. Numbers of the most abundant circulating cell type, neutrophils, were elevated at POST more so in CWI (p

Author(s): Krochmal, Patrick; Cooper, Dan M; Radom-Aizik, Shlomit; Lu, Kim D | Abstract: BackgroundLow physical fitness (PF) levels during childhood affect healthy growth and development, and increase the risk of cardiovascular diseases. Physical education standards exist for nearly all states in the United States, but evaluation of PF in youth has yet to be systematic, reproducible, and harmonized. The purpose of this project was to describe publicly available data of school-based PF testing (SB-PFT).MethodsA list of state-mandated SB-PFT programs published by SHAPE 2016 was confirmed by contacting appropriate authorities. SB-PFT data were obtained through each state's department of education.ResultsSixteen states mandate SB-PFT, with 10 states providing publicly available data; 92% to 100% of states perform the pacer/mile, curl-up, and push-up; 54.2% to 78.5% of elementary and 44% to 66.5% of high-school youth are in the "healthy fitness zone" for aerobic capacity.ConclusionsSB-PFT provided PF data in children across the United States. The variability and inconsistency in reporting and in the values, however, raises questions about the current status of SB-PFT data and its utility in assessing PF in children. The critical nature of PF assessments is highlighted in the current COVID-19 pandemic, during which physical education has been curtailed, and emerging data demonstrate worsening of the already low levels of PF in youth.

Author(s): Camplain, Ricky; Lopez, Nanette V; Cooper, Dan M; McKenzie, Thomas L; Zheng, Kai; Radom-Aizik, Shlomit | Abstract: IntroductionDuring the COVID-19 pandemic, some K-12 schools resumed in-person classes with varying degrees of mitigation plans in the fall 2020. Physical distancing and face coverings can minimize SARS-CoV-2 spread, the virus that causes COVID-19. However, no research has focused on adherence to mitigation strategies during school days. Thus, we sought to develop a systematic observation protocol to capture COVID-19 mitigation strategy adherence in school environments: The Systematic Observation of COVID-19 Mitigation (SOCOM).MethodsWe extended previously validated and internationally used tools to develop the SOCOM training and implementation protocols to assess physical-distancing and face-covering behaviors. SOCOM was tested in diverse indoor and outdoor settings (classrooms, lunchrooms, physical education [PE], and recess) among diverse schools (elementary, secondary, and special needs).ResultsFor the unique metrics of physical-distancing and face-covering behaviors, areas with less activity and a maximum of 10-15 students were more favorable for accurately capturing data. Overall proportion of agreement was high for physical distancing (90.9%), face covering (88.6%), activity type (89.2%), and physical activity level (87.9%). Agreement was lowest during active recess, PE, and observation areas with ≥20 students.ConclusionsMillions of children throughout the USA are likely to return to school in the months ahead. SOCOM is a relatively inexpensive research tool that can be implemented by schools to determine mitigation strategy adherence and to assess protocols that allow students return to school safely and slow the spread of COVID-19.

The impact of sickle cell anemia (SCA) and its complications on physical functioning and cardiopulmonary/aerobic fitness in affected individuals is significant. Although limited data support the safety of maximal cardiopulmonary exercise testing (CPET) for children and adults with SCA, the safety of submaximal moderate and high intensity, and longer duration, exercise in this population is not clear. The Sickle Cell Pro-Inflammatory Response to Interval Testing Study (SPRINTS) is a multicenter, randomized, prospective trial. SPRINTS leverages unique collaborations between investigators in pediatric hematology and exercise science to evaluate the impact of exercise intensity on the acute phase inflammatory response to exercise and changes in airway dynamics in children and young adults with SCA. Here we describe the study design and methodological strategies employed in SPRINTS, including an exercise challenge that mimics real-life patterns of childhood physical activity, characterized by multiple moderate and high intensity brief bouts of exercise interspersed with rest periods. Primary outcomes comprise pre- and post-exercise biomarkers of inflammation and endothelial dysfunction and spirometry. Secondary outcomes include assessment of physical activity and functioning, genomic studies and near-infrared spectroscopy measurements to assess tissue oxygenation status during exercise. SPRINTS aims to enroll 70 subjects with SCA and 70 matched, healthy controls. We anticipate that data from SPRINTS will address gaps in our understanding of exercise responses and safety in SCA and support the future development of evidence-based, exercise prescription guidelines in this population.

Purpose:Despite the known health benefits of physical activity (PA), few primary care pediatricians discuss, evaluate, or prescribe PA for children. The goal of this study was to examine pediatricians’ thoughts and practices related to child PA and the perceived facilitators and barriers to implementing PA evaluation and prescription in pediatric primary care clinics.Methods:The Consolidated Framework for Implementation Research was used to explore implementation barriers and facilitators. A mixed-method design combined questionnaires and focus groups with 27 pediatricians.Results:Despite the pediatricians’ beliefs that PA is important for patients, there was wide practice variability in their approaches to discussing PA. Several perceived barriers to implementing PA evaluation and prescription were identified, including lack of knowledge and training, managing time for PA with multiple demands, the need for a team approach and simple PA tools and resources, support for patient tailoring of PA messaging, and a need for PA best practice champions.Conclusion:The identified barriers to implementing evidence in PA suggest several directions for improvement, including a care-team approach; quick, inexpensive, and simple PA tools; community PA partnerships; PA training in medical education; evidence-based strategies; and PA directories for families. These efforts could facilitate the implementation of PA best practices in pediatrics.

Author(s): Cooper, Dan M; Girolami, Gay L; Kepes, Brenda; Stehli, Annamarie; Lucas, Candice Taylor; Haddad, Fadia; Zalidvar, Frank; Dror, Nitzan; Ahmad, Irfan; Soliman, Antoine; Radom-Aizik, Shlomit | Abstract: BackgroundHypothesis: neuromotor development correlates to body composition over the first year of life in prematurely born infants and can be influenced by enhancing motor activity.MethodsForty-six female and 53 male infants [27 ± 1.8 (sd) weeks] randomized to comparison or exercise group (caregiver provided 15-20 min daily of developmentally appropriate motor activities) completed the year-long study. Body composition [lean body and fat mass (LBM, FM)], growth/inflammation predictive biomarkers, and Alberta Infant Motor Scale (AIMS) were assessed.ResultsAIMS at 1 year correlated with LBM (r = 0.32, p l 0.001) in the whole cohort. However, there was no effect of the intervention. LBM increased by ~3685 g (p l 0.001)); insulin-like growth factor-1 (IGF-1) was correlated with LBM (r = 0.36, p = 0.002). IL-1RA (an inflammatory biomarker) decreased (-75%, p l 0.0125). LBM and bone mineral density were significantly lower and IGF-1 higher in the females at 1 year.ConclusionsWe found an association between neuromotor development and LBM suggesting that motor activity may influence LBM. Our particular intervention was ineffective. Whether activities provided largely by caregivers to enhance motor activity in prematurely born infants can affect the interrelated (1) balance of growth and inflammation mediators, (2) neuromotor development, (3) sexual dimorphism, and/or (4) body composition early in life remains unknown.

Purpose To examine the impact of polyphenol supplementation on the recruitment, mobilization, and activation of monocyte subsets after resistance exercise. Methods Thirty-eight recreationally active males (22.1 ± 3.1 yr; 173.9 ± 7.9 cm; 77.8 ± 14.5 kg) were assigned to 28 d of polyphenol blend (PPB) supplementation, placebo (PL), or control (CON). Blood samples were obtained before (PRE) postresistance exercise, immediately (IP) postresistance exercise, 1 h (1H) postresistance exercise, 5 h (5H) postresistance exercise, 24 h (24H) postresistance exercise, and 48 h (48H) postresistance exercise (PPB/PL) or rest (CON). Fine-needle biopsies were obtained from the vastus lateralis at PRE, 1H, 5H, and 48H. Circulating concentrations of macrophage chemoattractant protein-1 (MCP-1) and fractalkine, as well as intramuscular MCP-1 were analyzed via multiplex assay. Changes in the proportions and expression of CD11b on monocyte subsets were assessed via flow cytometry. Results Circulating MCP-1 increased in PPB and PL at IP with further increases at 5H. Intramuscular MCP-1 was increased at 1H, 5H, and 48H in all groups. Classical monocyte proportions were reduced in PPB and PL at IP, and increased at 1H. Nonclassical monocytes were increased in PPB and PL at IP, whereas intermediate monocytes were increased at IP, and reduced at 1H. Intermediate monocytes were increased in PPB at 24H and 48H. CD11b expression was reduced on PPB compared with PL and CON at PRE on intermediate and nonclassical monocytes. Conclusions Resistance exercise may elicit selective mobilization of intermediate monocytes at 24H and 48H, which may be mediated by tissue damage. Additionally, polyphenol supplementation may suppress CD11b expression on monocyte subsets at rest.

Advances in therapies have led to prolonged survival from many previously lethal health threats in children, notably among prematurely born babies and those with congenital heart disease. Evidence for catch-up growth is common in these children, but in many cases the adult phenotype is never achieved. A translational animal model is required in which specific tissues can be studied over a reasonable time interval. We investigated the impact of postnatal hypoxia (HY) (12%O2 (HY12) or 10% O2 (HY10)) on growth in rats relative to animals raised in room air. Subgroups had access to running wheels following the HY period. Growth was fully compensated in adult HY12 rats but not HY10 rats. The results of this study indicate that neonatal hypoxia can be a useful model for the elucidation of mechanisms that mediate successful catch-up growth following neonatal insults and identify the critical factors that prevent successful catch-up growth.

Introduction Aerobic fitness facilitates brain synaptic plasticity, which influences global and local sleep expression. While it is known that sleep patterns/behavior and non-rapid eye movement (NREM) sleep slow wave activity (SWA) tracks brain maturation, little is known about how aerobic fitness and sleep interact during development in youth. The aim of this pilot was to characterize relationships among aerobic fitness, measures of global/local sleep expression, and habitual sleep patterns in children and adolescents. We hypothesized that greater aerobic fitness would be associated with better sleep quality, indicated by increased SWA. Methods 20 adolescents (mean age=14.6±2.3 years old, range 11-17, 11 females) were evaluated for AF (peak VO2 assessed by ramp-type progressive cycle ergometry in the laboratory), habitual sleep duration and efficiency (continuous 7-14 day actigraphy with sleep diary), and topographic patterns of spectral power in slow wave, theta, and sleep spindle frequency ranges in non-rapid eye movement (NREM) sleep using overnight polysomnography with high-density electroencephalography (hdEEG, 128 channels). Results Significant relationships were observed between peak VO2 and habitual bedtime (r=-0.604, p=0.013) and wake-up time (r=-0.644, p=0.007), with greater fitness associated with an earlier sleep schedule (going to bed and waking up earlier). Peak VO2 was a significant predictor of slow oscillations (0.5-1Hz, p=0.018) and theta activity (4.5-7.5Hz, p=0.002) over anterior frontal and central derivations (p Conclusion Greater AF was associated with earlier habitual sleep times and with enhanced expression of developmentally-relevant sleep oscillations during NREM sleep. These data suggest that AF may 1) minimize the behavioral sleep delay commonly seen during adolescence, and 2) impact topographically-specific features of sleep physiology known to mechanistically support neuroplasticity and cognitive processes which are dependent on prefrontal cortex and hippocampal function in adolescents and adults. Support (if any) NCATS grant #UL1TR001414 & PERC Systems Biology Fund

BackgroundPoor aerobic fitness is associated with worsening of asthma symptoms, and fitness training may improve asthma control. The mechanism linking fitness with asthma is not known. We hypothesized that repeated bouts of exercise would lead to a downregulation of glucocorticoid receptor (GR) expression on circulating leukocytes, reflecting a reduced responsiveness to stress.MethodsIn a prospective exercise training intervention of healthy and asthmatic adolescents, GR expression in leukocytes was measured using flow cytometry in response to an acute exercise challenge before and after the exercise training intervention. Peripheral blood mononuclear cell (PBMC) gene expression of GR, GRβ, HSP70, TGFβ1, and TGFβ2 was determined using reverse-transcriptase PCR (RT-PCR).ResultsPeak VO2 increased by 14.6±2.3%, indicating an effective training (P

Introduction Aerobic fitness facilitates brain synaptic plasticity, which influences global and local sleep expression. While it is known that sleep patterns/behavior and non-rapid eye movement (NREM) sleep slow wave activity (SWA) tracks brain maturation, little is known about how aerobic fitness and sleep interact during growth and development in children and adolescents. The aim of this pilot study was to characterize relationships among aerobic fitness, measures of global/local sleep expression, and habitual sleep patterns in children and adolescents. We hypothesized that greater aerobic fitness would be associated with better sleep quality, indicated by increased SWA. Methods Twenty healthy youth (11-17 years-old, 11 female) were evaluated during summer vacation (no school schedule constraints). Aerobic fitness (VO2peak) was measured using ramp-type progressive cycle ergometry, habitual sleep (i.e., sleep-time consistency and circadian activity patterns) was assessed with 7-day actigraphy, and ad lib sleep was evaluated during overnight polysomnography (PSG) with high-density electroencephalography (hdEEG; 128 channels). Spectral analysis was implemented to quantify SWA (0.5-4.5Hz). Data were analyzed using linear regression analyses and exploratory independent samples t-tests. Results Negative correlations were observed between VO2peak and sleep measures including sleep-time consistency (partial r=-0.53, p=0.045) and timing/acrophase of the circadian activity rhythm (partial r=-0.64, p=0.01) while controlling for sex and age. Additionally, after accounting for Tanner stage and sex, data demonstrated significant effects in SWA at frontal derivations (p=0.024) between low and high fitness levels at topographically specific and meaningful EEG derivations, e.g. over frontal cortex. Conclusion These results suggest that children and adolescents with greater fitness have less variability in sleep-times (improved sleep consistency), tend to have a more advanced circadian activity phase (i.e., go to sleep earlier), and express greater frontal SWA, supporting the hypothesis that fitness is associated with improved local and global sleep quality. Future research with larger samples is necessary to further evaluate these relationships, and to determine if interventions that improve fitness also improve sleep and related brain plasticity. Support NCATS grant #UL1TR001414 & PERC Systems Biology Fund

Exercise provides a robust physiological stimulus that evokes cross-talk among multiple tissues that when repeated regularly (i.e., training) improves physiological capacity, benefits numerous organ systems, and decreases the risk for premature mortality. However, a gap remains in identifying the detailed molecular signals induced by exercise that benefits health and prevents disease. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to address this gap and generate a molecular map of exercise. Preclinical and clinical studies will examine the systemic effects of endurance and resistance exercise across a range of ages and fitness levels by molecular probing of multiple tissues before and after acute and chronic exercise. From this multi-omic and bioinformatic analysis, a molecular map of exercise will be established. Altogether, MoTrPAC will provide a public database that is expected to enhance our understanding of the health benefits of exercise and to provide insight into how physical activity mitigates disease.

Atherosclerosis originates in childhood and adolescence. The goal of this review is to highlight how exercise and physical activity during childhood and adolescence, critical periods of growth and development, can prevent adult cardiovascular disease (CVD), particularly through molecular mechanisms of monocytes, a key cell of the innate immune system. Monocytes are heterogeneous and pluripotential cells that can, paradoxically, play a role in both the instigation and prevention of atherosclerosis. Recent discoveries in young adults reveal that brief exercise affects monocyte gene pathways promoting a cell phenotype that patrols the vascular system and repairs injuries. Concurrently, exercise inhibits pro-inflammatory monocytes, cells that contribute to vascular damage and plaque formation. Because CVD is typically asymptomatic in youth, minimally invasive techniques must be honed to study the subtle anatomic and physiologic evidence of vascular dysfunction. Exercise gas exchange and heart rate measures can be combined with ultrasound assessments of vascular anatomy and reactivity, and near-infrared spectroscopy to quantify impaired O2 transport that is often hidden at rest. Combined with functional, transcriptomic, and epigenetic monocyte expression and measures of monocyte-endothelium interaction, molecular mechanisms of early CVD can be formulated, and then translated into effective physical activity-based strategies in youth to prevent adult-onset CVD.