Molecular Transducers of Physical Activity Consortium (MoTrPAC): Mapping the Dynamic Responses to Exercise.

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.

Whole-blood transcriptome analysis reveals distinct gene expression signatures in paediatric patients with sickle cell anaemia before and after exercise.

Sickle cell anaemia (SCA) patients display elevated levels of circulating pro-inflammatory cytokines and endothelial activation markers compared to healthy peers. The impact of exercise on the pro-inflammatory state in SCA remains unclear. This study aimed to characterize the whole-blood transcriptome profile in response to an acute bout of exercise in paediatric SCA patients. Twenty-three SCA participants (13 ± 3 years, 52% girls) and 17 healthy controls (14 ± 3 years, 29% girls) performed eight 2-min bouts of cycle ergometry interspersed with 1-min rest intervals. Whole-blood transcriptome profile (RNA-seq) was performed before and after exercise. At baseline, gene pathways associated with gas transport in erythrocytes were up-regulated in SCA patients compared to controls. Following exercise, gene pathways associated with innate immunity were altered in both groups. Interaction analyses revealed 160 annotated genes (101 up- and 59 down-regulated) that differentially altered by exercise in SCA patients. Moreover, genes that exhibited a blunted response to exercise in SCA patients were enriched in the IL-17 signalling pathway, suggesting an impaired innate immune response to exercise. This data will contribute to the development of evidence-based exercise prescription guidelines for this patient population.

Targeted proteomics involved in cardiovascular health and heart rate variability in children with overweight/obesity.

BACKGROUND: Children with overweight/obesity often exhibit alterations in their plasma protein profiles and reduced heart rate variability (HRV). Plasma proteomics is at the forefront of identifying biomarkers for various clinical conditions. We aimed to examine the association between plasma-targeted proteomics involved in cardiovascular health and resting vagal-related HRV parameters in children with overweight/obesity. METHODS: Forty-four children with overweight/obesity (10.2 ± 1.1 years old; 52% boys) participated in the study. Olink's technology was used to quantify 92 proteins involved in cardiovascular health. HRV was measured using a heart rate monitor (Polar RS800CX). Four resting vagal-related HRV parameters were derived in time- and frequency-domain. RESULTS: Eight proteins (KIM1, IgG Fc receptor II-b, IDUA, BOC, IL1RL2, TNFRSF11A, VSIG2, and TF) were associated with at least one out of the four vagal-related HRV parameters (ß values ranging from -0.188 to 0.288; all p < .05), while KIM1, IDUA, and BOC associated with ≥ three vagal-related HRV parameters. Multiple hypothesis testing corrections did not reach statistical significance (false discovery rate [FDR >0.05]). CONCLUSION: Plasma-targeted proteomics suggested novel biomarkers for resting vagal-related HRV parameters in children with overweight/obesity. Future studies using larger cohorts and longitudinal designs should confirm our findings and their potential clinical implications.

Effects of exercise on whole-blood transcriptome profile in children with overweight/obesity.

BACKGROUND: The current knowledge about the molecular mechanisms underlying the health benefits of exercise is still limited, especially in childhood. We set out to investigate the effects of a 20-week exercise intervention on whole-blood transcriptome profile (RNA-seq) in children with overweight/obesity. METHODS: Twenty-four children (10.21 ± 1.33 years, 46% girls) with overweight/obesity, were randomized to either a 20-week exercise program (intervention group; n = 10), or to a no-exercise control group (n = 14). Whole-blood transcriptome profile was analyzed using RNA-seq by STRT technique with GlobinLock technology. RESULTS: Following the 20-week exercise intervention program, 161 genes were differentially expressed between the exercise and the control groups among boys, and 121 genes among girls (p-value <0.05), while after multiple correction, no significant difference between exercise and control groups persisted in gene expression profiles (FDR >0.05). Genes enriched in GO processes and molecular pathways showed different immune response in boys (antigen processing and presentation, infections, and T cell receptor complex) and in girls (Fc epsilon RI signaling pathway) (FDR <0.05). CONCLUSION: These results suggest that 20-week exercise intervention program alters the molecular pathways involved in immune processes in children with overweight/obesity.

Safety of maximal cardiopulmonary exercise testing in individuals with sickle cell disease: a systematic review.

OBJECTIVE: We 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. DESIGN: Systematic review. DATA SOURCES: Systematic 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 STUDIES: Two 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. RESULTS: In 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. CONCLUSION: Maximal 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.

Clinical evaluation of a novel subcutaneous lactate monitor.

Lactate levels are commonly used as an indirect measure to assess metabolic stress in clinical conditions like sepsis. Dynamic lactate measurements are recommended to assess and guide treatment in patients with shock and other critical care conditions. A minimally invasive, continuous lactate monitor has potential to improve clinical decisions and patient care. The purpose of the study was to evaluate continuous lactate measurements of a novel enzymatic Continuous Lactate Monitor (CLM) developed in our laboratory. Lactate levels were monitored during incremental cycling exercise challenges as a tool for hyperlactatemia. Six healthy individuals 18-45 y/o (4 males, 2 females) participated in the study. CLM devices were inserted subcutaneously in the postero-lateral trunk below the renal angle, one hour before the exercise challenge. Each exercise challenge consisted of a 3 to 12-min warm up period, followed by up to 7, 4-min incremental workload bouts separated by rest intervals. Continuous lactate measurements obtained from CLM were compared with commercial lactate analyzer (Abbott iSTAT) measurements of venous blood (plasma) drawn from the antecubital vein. Blood was drawn at up to 25 time points spanning the duration of before exercise, during exercise, and up to 120 min post exercise. Area under the curve (AUC), and delay time were calculated to compare the CLM readings with plasma lactate concentration. Average plasma lactate concentration increased from 1.02 to 16.21 mM. Ratio of AUC derived from CLM to plasma lactate was 1.025 (0.990-1.058). Average dynamic delay time of CLM to venous plasma lactate was 5.22 min (2.87-10.35). Insertion sites examined 48 h after CLM removal did not show signs of side effects and none required medical attention upon examination. The newly developed CLM has shown to be a promising tool to continuously measure lactate concentration in a minimally invasive fashion. Results indicate the CLM can provide needed trends in lactate over time. Such a device may be used in the future to improve treatment in clinical conditions such as sepsis.

Kids With Altitude: Acute Mountain Sickness and Changes in Body Mass and Total Body Water in Children Travelling to 3800 m.

INTRODUCTION: 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 (SpO2) during 1 week of acclimatization to 3800 m. METHODS: In 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), SpO2 (pulse oximetry), AMS (Lake Louise Questionnaire), and ELW (transthoracic echocardiography) were measured. RESULTS: No differences were found between children and adults in SpO2 or ELW. At 3800 m 7 of 10 children were AMS+ vs 4 of 10 adults. Among those AMS+ at 3800 m, the severity was greater in children compared to adults (5±1 vs 3 ± 0; P=0.005). Loss of body mass occurred more quickly in children (day 5 vs day 7) and to a greater extent (-7±3% vs -2±2%; P<0.001); these changes were mediated via a larger relative loss in total body water in children than in adults (-6±5% vs -2±2%; P=0.027). CONCLUSIONS: Children 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.

Distinct whole-blood transcriptome profile of children with metabolic healthy overweight/obesity compared to metabolic unhealthy overweight/obesity.

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.

SARS-CoV-2 vaccine testing and trials in the pediatric population: biologic, ethical, research, and implementation challenges.

As the nation implements SARS-CoV-2 vaccination in adults at an unprecedented scale, it is now essential to focus on the prospect of SARS-CoV-2 vaccinations in pediatric populations. To date, no children younger than 12 years have been enrolled in clinical trials. Key challenges and knowledge gaps that must be addressed include (1) rationale for vaccines in children, (2) possible effects of immune maturation during childhood, (3) ethical concerns, (4) unique needs of children with developmental disorders and chronic conditions, (5) health inequities, and (6) vaccine hesitancy. Because COVID-19 is minimally symptomatic in the vast majority of children, a higher acceptable risk threshold is required when evaluating pediatric clinical trials. Profound differences in innate and adaptive immunity during childhood and adolescence are known to affect vaccine responsiveness for a variety of childhood diseases. COVID-19 and the accompanying social disruption, such as the school shutdowns, has been disproportionately damaging to minority and low-income children. In this commentary, we briefly address each of these key issues, specify research gaps, and suggest a broader learning health system approach to accelerate testing and clinical trial development for an ethical and effective strategy to implement a pediatric SARS-CoV-2 vaccine as rapidly and safely as possible. IMPACT: As the US begins an unprecedented implementation of SARS-CoV-2 vaccination, substantial knowledge gaps have yet to be addressed regarding vaccinations in the pediatric population. Maturational changes in the immune system during childhood have influenced the effectiveness of pediatric vaccines for other diseases and conditions, and could affect SARS-CoV-2 vaccine responsiveness in children. Given that COVID-19 disease is far milder in the majority of children than in adults, the risk-benefit of a pediatric SARS-CoV-2 vaccine must be carefully weighed. The needs of children with developmental disabilities and with chronic disease must be addressed. Minority and low-income children have been disproportionately adversely affected by the COVID-19 pandemic; care must be taken to address issues of health equity regarding pediatric SARS-CoV-2 vaccine trials and allocation. Research and strategies to address general vaccine hesitancy in communities must be addressed in the context of pediatric SARS-CoV-2 vaccines.

SARS-CoV-2 acquisition and immune pathogenesis among school-aged learners in four diverse schools.

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 < 0.01) and IgG positivity rates (13/66, 19.7%). School D (93% on-site learners) had the lowest infection and IgG positivity rates (1/63, 1.6%). Mitigation compliance [physical distancing (mean 87.4%) and face-covering (91.3%)] was remarkably high at all schools. Documented SARS-CoV-2-infected learners had neutralizing antibodies (94.7%), robust IFN-γ + T cell responses, and reduced monocytes. 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.

Cardiorespiratory fitness in children with overweight/obesity: Insights into the molecular mechanisms.

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. VO2 peak 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.

Exploration of Barriers and Facilitators to Implementing Best Practice in Exercise Medicine in Primary Pediatric Care-Pediatrician Perspectives.

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.

Exercise-associated prevention of adult cardiovascular disease in children and adolescents: monocytes, molecular mechanisms, and a call for discovery.

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.

Body composition and neuromotor development in the year after NICU discharge in premature infants.

BACKGROUND: Hypothesis: neuromotor development correlates to body composition over the first year of life in prematurely born infants and can be influenced by enhancing motor activity. METHODS: Forty-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. RESULTS: AIMS at 1 year correlated with LBM (r = 0.32, p < 0.001) in the whole cohort. However, there was no effect of the intervention. LBM increased by ~3685 g (p < 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 < 0.0125). LBM and bone mineral density were significantly lower and IGF-1 higher in the females at 1 year. CONCLUSIONS: We 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.

A new approach to estimate aerobic fitness using the NHANES dataset.

INTRODUCTION: Physical activity and fitness are essential for healthy growth in children. The National Health and Nutrition Examination Survey (NHANES) evaluated fitness by estimating V̇O2 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 V̇O2 max correlated with actual VO2 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 V̇O2 max and examined their relationship to cardiovascular risk factors (BMI percentiles and lipid levels). RESULTS: Measured V̇O2 peak was moderately correlated with NHANES estimated V̇O2 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 V̇O2 max accounted for approximately 28% of the variability in the measured V̇O2 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.

Expert's Choice: 2018's Most Exciting Research in the Field of Pediatric Exercise Science.

This commentary highlights 23 noteworthy publications from 2018, selected by leading scientists in pediatric exercise science. These publications have been deemed as significant or exciting in the field as they (a) reveal a new mechanism, (b) highlight a new measurement tool, (c) discuss a new concept or interpretation/application of an existing concept, or (d) describe a new therapeutic approach or clinical tool in youth. In some cases, findings in adults are highlighted, as they may have important implications in youth. The selected publications span the field of pediatric exercise science, specifically focusing on: aerobic exercise and training; neuromuscular physiology, exercise, and training; endocrinology and exercise; resistance training; physical activity and bone strength; growth, maturation, and exercise; physical activity and cognition; childhood obesity, physical activity, and exercise; pulmonary physiology or diseases, exercise, and training; immunology and exercise; cardiovascular physiology and disease; and physical activity, inactivity, and health.

Inter- and intra-subject variability of nitric oxide levels in leukocyte subpopulations.

Assessment of nitric oxide (NO) dynamics in immune cells, commonly measured using NO surrogates such as inducible nitric oxide synthase (iNOS) rather than NO itself, has been effective in understanding pathophysiology across a wide range of diseases. Although the intracellular measurement of NO is now feasible, many technical issues remain unresolved. The principle aim of our study was to determine the effect of storage time of whole blood on nitric oxide (NO) level expression in leukocytes. This is important because immune cells remain chemically dynamic even after they are removed from the circulation, and the impact of storage time must be known to optimally quantify the effect of a disease or condition on NO dynamics in circulating leukocytes. We measured NO levels using the fluorescent probe, diaminofluorescein (DAF-2DA), and flow cytometry in monocytes, neutrophils, and natural killer cells from healthy subjects immediately after blood draw (Time 0) and 30, 60, and 120 min following the blood draw. There was no significant difference among the 4 study time points in NO (DAF-2) levels, though there was wide intra-subject variability at all time points. Using LPS stimulation, we compared iNOS (the more traditional surrogate marker of NO dynamics) with NO (by DAF-2) in natural killer cells and monocytes and, we found no difference in the response patterns. In summary, we did find that within a 2-hour interval from blood draw to sample processing, there was a remarkably wide intra-subject variability in expression of intracellular NO (DAF-2) in leukocytes of healthy individuals at baseline and over time. The mechanism(s) for these differences are not known but could clearly confound efforts to detect changes in NO metabolism in white blood cells. We speculate that rapid pulsatility of NO could explain the wide variability seen.

Glucocorticoid receptor expression on circulating leukocytes in healthy and asthmatic adolescents in response to exercise.

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, GRß, HSP70, TGFß1, and TGFß2 was determined using reverse-transcriptase PCR (RT-PCR).ResultsPeak VO2 increased by 14.6±2.3%, indicating an effective training (P<0.01). There was a significant difference in GR expression among leukocyte subtypes, with highest expression in eosinophils. Following the exercise training intervention, there was a significant decrease in baseline GR expression (P<0.05) in leukocyte and monocyte subtypes in both healthy and asthmatic adolescents.ConclusionsThis is the first study in adolescents to show that exercise training reduces GR expression in circulating leukocytes. We speculate that exercise training downregulates the stress response in general, manifested by decreased GR expression, and may explain why improving fitness improves asthma health.

Immune Response to Exercise During Growth.

Two papers were selected for this commentary. The first paper (Citation 1) suggests that a 10-week, moderate-intensity exercise program performed early after allogeneic hematopoietic stem cell transplantation is feasible in this fragile population, and might improve cell cytotoxicity by redistributing subpopulations of NK cells. This study adds to the growing evidence that enhancing immune cell surveillance (e.g., NK cells) in response to exercise could benefit cancer patients. The second paper (Citation 2) studied neutrophil-related mediators of oxidative stress and inflammatory cytokines in response to exercise in children compared with adults. The authors found age/maturation-related differences in these responses. The paper provides a valuable introduction to the current knowledge of maturational changes in immune mediators' response to exercise. Data about leukocyte function in response to exercise in healthy children and in children with clinical conditions is scant. The need for prospective large scale pediatric clinical exercise studies is clear. Molecular approaches to understand the mechanisms through which physical activity can improve health will help to shape guidelines that optimize the mode, frequency, intensity, and duration of the training intervention.

Assessing Parent Perceptions of Physical Activity in Families of Toddlers With Neurodevelopmental Disorders: The Parent Perceptions of Physical Activity Scale (PPPAS).

PURPOSE: The purpose of this study was to examine a new tool (PPPAS = Parent Perceptions of Physical Activity Scale-Preschool) developed to study parental perceptions of physical activity (PA) among parents of toddler and preschool age children. METHOD: 143 children (mean age 31.65 months; 75% male) and their parents were recruited from a neurodevelopmental clinic. Parents completed questionnaires, and both a psychologist and a physician evaluated the children. Eighty-three percent of the children received a diagnosis of Autism Spectrum Disorder; 20% of the children had a BMI > 85th percentile. Analyses were conducted to evaluate the reliability, concurrent validity, discriminant validity, and predictive validity of PPPAS scores. RESULTS: Results supported a two-factor structure: Perceptions of the Benefits of PA and the Barriers to PA. The internal consistency of scores was good for both PPPAS subscales, derived from the two factors. Parent perceptions of barriers to PA were significantly correlated with delays in overall adaptive functioning, daily living skills, socialization, and motor skills. When a child's motor skills were delayed, parents were less likely to believe PA was beneficial and perceived more barriers to PA. Parent perceptions of barriers to PA predicted parent-reported weekly unstructured PA and ratings of how physically active their child was compared with other children. CONCLUSION: We present the PPPAS-Preschool for use in pediatric exercise research and discuss potential applications for the study of parent perceptions of PA in young children.