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Standard cardiopulmonary exercise testing (CPET) produces a rich dataset but its current analysis is often limited to a few derived variables such as maximal or peak oxygen uptake (V̇O2). We tested whether breath‐by‐breath CPET data could be used to determine sample entropy (SampEn) in 81 healthy children and adolescents (age 7–18 years old, equal sex distribution). To overcome challenges of the relatively small time‐series CPET data size and its nonstationarity, we developed a Python algorithm for short‐duration physiological signals. Comparing pre‐ and post‐ventilatory threshold (VT1) CPET phases, we found: (1) SampEn decreased by 9.46% for V̇O2 and 5.01% for V̇CO2 (p < 0.05), in the younger, early‐pubertal participants; and (2) HR SampEn fell substantially by 70.8% in the younger and 77.5% in the older participants (p < 0.001). Across all ages, females exhibited greater HR SampEn than males during both pre‐ and post VT1 CPET phases by 14.10% and 23.79%, respectively, p < 0.01. In females, late‐pubertal had 17.6% lower HR SampEn compared to early‐pubertal participants (p < 0.05). Breath‐by‐breath gas exchange and HR data from CPET are amenable to SampEn analysis that leads to novel insight into physiological responses to work intensity, and sex and maturational effects. [ABSTRACT FROM AUTHOR]

Natural patterns of physical activity in youth are characterized by brief periods of exercise of varying intensity interspersed with rest. To better understand systemic physiologic response mechanisms in children and adolescents, we examined five responses [heart rate (HR), respiratory rate (RR), oxygen uptake (V̇O2), carbon dioxide production (V̇CO2), and minute ventilation (V̇E), measured breath‐by‐breath] to multiple brief exercise bouts (MBEB). Two groups of healthy participants (early pubertal: 17 female, 20 male; late‐pubertal: 23 female, 21 male) performed five consecutive 2‐min bouts of constant work rate cycle‐ergometer exercise interspersed with 1‐min of rest during separate sessions of low‐ or high‐intensity (~40% or 80% peak work, respectively). For each 2‐min on‐transient and 1‐min off‐transient we calculated the average value of each cardiopulmonary exercise testing (CPET) variable (Y̅). There were significant MBEB changes in 67 of 80 on‐ and off‐transients. Y̅ increased bout‐to‐bout for all CPET variables, and the magnitude of increase was greater in the high‐intensity exercise. We measured the metabolic cost of MBEB, scaled to work performed, for the entire 15 min and found significantly higher V̇O2, V̇CO2, and V̇E costs in the early‐pubertal participants for both low‐ and high‐intensity MBEB. To reduce breath‐by‐breath variability in estimation of CPET variable kinetics, we time‐interpolated (second‐by‐second), superimposed, and averaged responses. Reasonable estimates of τ (<20% coefficient of variation) were found only for on‐transients of HR and V̇O2. There was a remarkable reduction in τHR following the first exercise bout in all groups. Natural patterns of physical activity shape cardiorespiratory responses in healthy children and adolescents. Protocols that measure the effect of a previous bout on the kinetics of subsequent bouts may aid in the clinical utility of CPET. [ABSTRACT FROM AUTHOR]

BACKGROUND Low 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). METHODS: A 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. RESULTS: Sixteen 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. CONCLUSIONS: SB‐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. [ABSTRACT FROM AUTHOR]

Introduction: Physical activity and fitness are essential for healthy growth in children. The National Health and Nutrition Examination Survey (NHANES) evaluated fitness by estimating V̇O2max from submaximal measurements of heart rate (HR) during graded treadmill exercise. Our aims were (a) to examine how well NHANES methodology used to estimate V̇O2max correlated with actual VO2max 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 V̇O2max and examined their relationship to cardiovascular risk factors (BMI percentiles and lipid levels). Results: Measured V̇O2peak was moderately correlated with NHANES estimated V̇O2max (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 V̇O2max accounted for approximately 28% of the variability in the measured V̇O2peak. 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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]

Human research projects must have a scientifically valid study design, analytic plan, and be operationally feasible in order to be successfully completed and thus to have translational impact. To ensure this, institutions that conduct clinical research should have a scientific review process prior to submission to the Institutional Review Committee (IRB). This paper reports the Clinical and Translational Science Award (CTSA) Consortium Scientific Review Committee (SRC) Consensus Working Group's proposed framework for a SRC process. Recommendations are provided for institutional support and roles of CTSAs, multisite research, criteria for selection of protocols that should be reviewed, roles of committee members, application process, and committee process. Additionally, to support the SCR process effectively, and to ensure efficiency, the Working Group recommends information technology infrastructures and evaluation metrics to determine outcomes are provided. [ABSTRACT FROM AUTHOR]

Inhaled corticosteroids (ICS) and β2-agonists are the primary pharmacotherapies of asthma management. However, suboptimal medication compliance is common in asthmatics and is associated with increased morbidity. We hypothesized that exhaled breath measurements of the aerosol used in the inhaled medications might prove useful as surrogate marker for asthma medication compliance. To explore this, 10 healthy controls were recruited and randomly assigned to ICS (Flovent HFA) or short acting bronchodilators (Proventil HFA). Both inhalers contain HFA-134a as aerosol propellant. Exhaled breath sampling and pulmonary function tests were performed prior to the inhaler medication dispersion, immediately after inhalation, then at 2, 4, 6, 8, 24, and 48 hours postadministration. At baseline, mean (SD) levels of HFA-134a in the breath were 252 (156) pptv. Immediately after inhalation, HFA-134a breath levels increased to 300 × 106 pptv and were still well above ambient levels 24 hours postadministration. The calculated ratio of forced expiratory volume in 1 second over forced vital capacity did not change over time following inhaler administration. This study demonstrates, for the first time, that breath HFA-134a levels can be used to assess inhaler medication compliance. It may also be used to evaluate how effectively the medicine is delivered. [ABSTRACT FROM AUTHOR]

In children, levels of play, physical activity, and fitness are key indicators of health and disease and closely tied to optimal growth and development. Cardiopulmonary exercise testing (CPET) provides clinicians with biomarkers of disease and effectiveness of therapy, and researchers with novel insights into fundamental biological mechanisms reflecting an integrated physiological response that is hidden when the child is at rest. Yet the growth of clinical trials utilizing CPET in pediatrics remains stunted despite the current emphasis on preventative medicine and the growing recognition that therapies used in children should be clinically tested in children. There exists a translational gap between basic discovery and clinical application in this essential component of child health. To address this gap, the NIH provided funding through the Clinical and Translational Science Award (CTSA) program to convene a panel of experts. This report summarizes our major findings and outlines next steps necessary to enhance child health exercise medicine translational research. We present specific plans to bolster data interoperability, improve child health CPET reference values, stimulate formal training in exercise medicine for child health care professionals, and outline innovative approaches through which exercise medicine can become more accessible and advance therapeutics across the broad spectrum of child health. [ABSTRACT FROM AUTHOR]

The article profiles the University of California in Irvine, California. It states that the university is a young and dynamic educational institution with student population of 22,000 undergraduates and 5,000 graduates. It notes that they aims to catalyze the generation of innovative methods and technologies that improve the development, testing, and implementation of diagnostics and therapeutics. It mentions that they plan to reconfigure its vision and support translational research.

MicroRNAs are increasingly seen as targets of drug discovery because they influence gene function acting both to silence and subtly modulate protein translation. Little is known about effects of dynamic physiological states on microRNA regulation in humans. We hypothesized that microRNA expression in peripheral blood mononuclear cells (PBMCs) would be affected by brief exercise. Twelve young men performed brief bouts of heavy exercise. PBMC microRNA was analyzed before and immediately after exercise using the Agilent Human microRNA V2 Microarray. Exercise altered expression level of 34 microRNAs (FDR < 0.05). Many of them play roles in inflammatory processes (e.g., miR-125b[↓], down-regulated by proinflammatory factor LPS; and miR-132[↑], 125b[↓] and let-7e[↓] involved inTLR4 signaling). Using previous exercise data in PBMCs, we linked the microRNA changes to specific gene pathways. This analysis identified 12 pathways including the TGF-β and MAPK signaling. We also compared exercise-associated microRNA changes in PBMCs with the exercise-associated microRNAs previously identified in neutrophils. Nine microRNAs were affected in both PBMCs and neutrophils, but only six changed in the same direction. A commonly occurring physiologic perturbation, brief heavy exercise, changes microRNA profiles in PBMCs, many of which are related to inflammatory processes. The pattern of change suggests that exercise differentially influences microRNAs in leukocyte subtypes. Clin Trans Sci 2012; Volume #: 1-7 [ABSTRACT FROM AUTHOR]

Epidemiological, clinical, physiological, cellular, and molecular evidence suggests that the origins of obesity and metabolic dysfunction can be traced back to intrauterine life and supports an important role for maternal nutrition prior to and during gestation in fetal programming. The elucidation of underlying mechanisms is an area of interest and intense investigation. In this perspectives paper we propose that in addition to maternal nutrition-related processes it may be important to concurrently consider the potential role of intrauterine stress and stress biology. We frame our arguments in the larger context of an evolutionary-developmental perspective that supports roles for both nutrition and stress as key environmental conditions driving natural selection and developmental plasticity. We suggest that intrauterine stress exposure may interact with the nutritional milieu, and that stress biology may represent an underlying mechanismmediating the effects of diverse intrauterine perturbations, including but not limited to maternal nutritional insults (undernutrition and overnutrition), on brain and peripheral targets of programming of body composition, energy balance homeostasis, and metabolic function.We discuss putative maternal-placentalfetal endocrine and immune/inflammatory candidate mechanisms that may underlie the long-term effects of intrauterine stress. We conclude with a commentary of the implications for future research and clinical practice. [ABSTRACT FROM AUTHOR]

The article presents a study which aims to determine possible correlations of measurements acquired through the examination of body components of preterm and term newborns. 102 preterm and term infants ready for gestation were the subject of a series of tests conducted through the use of dual X-ray absorptiometry (DXA), limb ultrasound and bone quantitative ultrasound. Little correlation is observed from measurements of bone strength when compared with DXA acquired bone mineral density (BMD).

The article discusses research being done on obesity in adolescent females. It references a study by Margaret Schneider et al published in the 2007 issue of "Obesity." Television and interactive media are evaluated to have a role in the obesity problem of adolescents. The results of a multivariate regression analysis model showed the association of interactive media with obesity.

Purpose To compare the incidence rates of diabetes mellitus and dyslipidemia in ambulatory first-time users of risperidone and olanzapine. Methods The database for the Prescription Drug Insurance Plan in the province of Quebec was used as the data source for a population-based cohort study. Denominalized data were extracted for all ambulatory patients who first received an atypical antipsychotic between 1 January 1997 and 31 August 1999. Eligible patients were categorized as taking: no antidiabetic medication; no lipid reducing medication; neither type of medication. Those who started to use an outcome drug (an antidiabetic or lipid-lowering medication) before the end of the follow-up period (31 August 2000) were considered to have developed the corresponding outcome disease. Incidence rate ratios (IRR) (and 95% confidence intervals) for initiating antihyperglycemic or lipid-lowering drug treatment, or both were calculated. Outcomes on risperidone were compared to those on olanzapine. Results A total of 19 582 eligible patients were included in the analysis. Relative to risperidone, olanzapine was associated with a higher risk of initiating a pharmacologic treatment for diabetes [IRR: 1.33 (1.03-1.74)], dyslipidemia [IRR: 1.49 (1.22-1.83)], or either condition [1.47 (1.23-1.76)]. Conclusions Olanzapine seems to be associated with a higher risk of developing diabetes and/or dyslipidemia than risperidone. Further prospective studies are needed to rigorously assess the safety of olanzapine. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

OBJECTIVEInsulin-like growth factor-I (IGF-I) levels are lower in older compared with younger subjects. We tested the hypothesis that the reduction in circulating IGF-I would be accompanied by upregulation in tissue IGF-I binding in at least some tissues. We tested erythrocyte IGF-I binding since blood is an accessible tissue in humans, and there is growing evidence to suggest that erythrocyte IGF-I binding is influenced by circulating IGF-I. DESIGN AND PATIENTSWe compared 9 healthy older males (61–68 years old) with 9 healthy younger males (15–19 years old). MEASUREMENTSStandard techniques were used to assay circulating IGF-I and IGF binding proteins 1–5 (IGFBPs 1–5). Erythrocyte IGF-I binding was first measured by studies in which native [125I]-IGF-I was displaced with unlabelled native IGF-I. In order to determine a possible role for IGF binding proteins (IGFBP), native [125I]-IGF-I was displaced with des-(1-3)IGF-I, which binds with IGF receptors but not IGFBPs. RESULTSAs expected, circulating IGF-I was significantly lower in the older compared with the younger subjects. In addition, IGFBP-3 and 5 were significantly lower, and IGFBP-4 higher, in older compared with younger subjects. When native [125I]-IGF-I was displaced with unlabelled native IGF-I, the number of IGF-I binding sites per erythrocyte was higher in the older subjects (43 ± 5 vs. 18 ± 2, older vs. younger, respectively; P < 0.05). In contrast, when native [125I]-IGF-I was displaced with des-(1-3), IGF-I binding capacity was not different between the two age groups. CONCLUSIONSErythrocyte IGF binding was increased in older compared with younger subjects. Surprisingly, the mechanism of the increase may not be a simple up regulation of IGF-I receptors in response to reduced circulating IGF-I, but possibly by an increase in the levels of as yet unidentified erythrocyte membrane-associated IGF binding proteins. [ABSTRACT FROM AUTHOR]

The article presents a study to examine the information activities of firms during periods of vulnerability in order to gain increased understanding of corporate behavior during intervals of increased risk. This study identifies firm manipulation of voluntary information announcements during periods of vulnerability. The periods of vulnerability identified were the time-spans between (1) the announcement of intent to issue new seasoned equity and (2) the conversion period following the announcement of a call on convertible debt. These periods represent intervals of time when the firm is particularly sensitive to negative pressure on the share price. A probability model was employed to compute expected levels of news announcements during the period following announcement. The study also differentiated between underwritten and non-underwritten convertible debt. Results suggest that firms employing underwritten convertible debt do not have the same motivation to withhold information. This is consistent with an insurance interpretation of the decision to underwrite. Firms which are unable or unwilling to purchase underwriting services appear to be more likely to manage voluntary information flows.

To examine the impact of brief exercise in early pubertal (EP) and late pubertal (LP) males on intracellular levels of cytokines and growth in circulating blood. Many of the health effects of exercise are influenced by the balance of stress/inflammatory related cytokines (e.g., IL-6 & TNFα) and growth factors (e.g., GH & IGF-1) that are known to be altered by physical activity. Flow cytometry is used routinely to assess changes in intracellular protein production and to identify the specific leukocyte subsets. To our knowledge, no studies have focused on the effect of exercise on intracellular mediators in children. Methods: 14-EP and 9-LP males, performed an exercise consisting of 10 two-min, bouts of constant cycle ergometry with one-min. rest interval between each bout of exercise. Blood was sampled at baseline and at the end-exercise. Flow cytometry was used to detect the percent of leukocytes positive for intracellular proteins. Conclusions: Exercise caused a differential expression of intracellular mediators in EP and LP males. These intracellular signaling patterns may be essential in preparing the organism to adapt to stressors imposed by exercise and may be influenced by pubertal status. [ABSTRACT FROM AUTHOR]

Even with brief bouts of exercise, circulating neutrophils rapidly increase, but whether or not this is accompanied by altered gene expression is not known. We hypothesized that exercise would particularly influence families of genes involved in stress and inflammation. 12 healthy men (19-29 yr old) performed 30-min constant work rate cycle ergometry (∼80% peak VO2), and neutrophils were isolated before and after. RNA was hybridized to Affymetrix U133+ 2.0 Genechip arrays. Differential gene expression was determined using stringent criteria (FDR<0.05, t-test p<0.0016). Neutrophils increased after exercise (43.5±9.2%, p<0.0001). Significant changes in expression were observed in 647 genes (up in 364). Genes related to cytokine binding and receptors (e.g., IL2RB, IL2RG, TNFL8, IL18RAP and I10R1), the Hsp family, and the immune response (e.g., CCR5, IL32 and IL18RAP) had higher expression. In contrast, genes that induce apoptosis (e.g., GADD45B, TNFSF10, and BCLAF1) had lower expression, consistent with the increased expression of MCL1, a gene involved in inhibiting apoptosis. The gene profile of circulating neutrophils dynamically changes with common activities like exercise. Neutrophils play key roles in pathogenesis of diseases like atherosclerosis and asthma. Exercise might influence these conditions by first altering neutrophil function at the level of gene expression. [ABSTRACT FROM AUTHOR]

It now appears that many of the health effects of exercise are influenced by the balance of stress mediators and growth factors. Related to these agents are the soluble adhesion molecules (sAM: ICAM and VCAM) and soluble selectins (sS: E, L and P-selectins) which have been linked to such illnesses as asthma and cardiovascular disease. We hypothesized that brief exercise would alter circulating levels of sAM and sS, and that the response would be modified by the child's pubertal status. 30 healthy males (14 early pubertal, EP; 16 late pubertal, LP) performed 10 2-min bouts of exercise on a cycle ergometer. Blood was sampled at pre-exercise (PE) and end-exercise (EE). Levels of sAM and sS were analyzed using commercially available ELISAs. Mean PE levels were significantly different between groups for ICAM (p<0.005) and VCAM (p<0.05) and at EE for ICAM (p<0.005). VCAM significantly increased in response to exercise in LP males (p<0.05). A significant change between groups was demonstrated for the selectins at PE (E and P p<0.005; L p<0.05) and EE (all sS p<0.05). Only LP males demonstrated a significant change from PE to EE (all sS p<0.05). Baseline levels of circulating vascular adhesion molecules are significantly different between healthy EP and LP males. Moreover, exercise in LP males caused a significant increase in these vascular mediators, possibly preparing the organism to adapt to stressors imposed by exercise and the vascular demands needed for muscle growth. [ABSTRACT FROM AUTHOR]

In patients with cystic fibrosis (CF), physical fitness is associated with enhanced longevity and improved quality of life even though cardiorespiratory responses to exercise are abnormal. Studies in CF children typically utilize prolonged or maximal exercise, protocols that do not mimic real life patterns of physical activity. We hypothesized that abnormal responses to brief exercise would occur in CF and that the abnormalities would worsen with repeated bouts. 12 CF (mild-moderate) and 39 control participants (range 9 to 15 y.o.) performed a series of 2-min constant work rate cycle ergometry (with 1-min rest intervals) at a work rate equivalent to about 70% peak. Gas exchange was measured breath-by-breath. We applied linear mixed models with quadratic form of Bout (1 to 9) and Time (1 to 2 minutes) for statistical analysis. Significant differences were found in a number of key parameters. For example, VE (Figure--group mean data) in both groups progressively increased. In CF, VE was consistently higher and recovery from each bout was prolonged. Abnormal responses were also observed for VO2 and HR. While control subjects easily completed 10 bouts, most CF subjects stopped exercise after 9. In conclusion, brief repeated bouts of exercise lead to progressive change in the kinetics of key cardiorespiratory responses in both healthy children and those with CF. In CF responses are abnormal and worsen. Ventilatory responses to exercise change dynamically and quickly in children. Prolonged recovery even after brief exercise bouts in CF children may contribute to exercise intolerance. [ABSTRACT FROM AUTHOR]

Exercise-induced leukocytosis is a striking and consistent observation. We hypothesized that pre-exercise (PreE) leukocyte levels could explain much of the variation in exercise neutrophilia. The contribution of asthma, fitness, exercise duration and PreE leukocyte levels to exercise-induced neutrophilia was analyzed using regression. Healthy (n=80) and asthmatic (n=26) children completed either 8 or 30-min of exercise at 85% of max capacity. Fitness measures included VO2max and %BF by DEXA. Blood was collected 30-min after IV placement (PreE) and immediately after exercise (PostE). Total leukocyte increased 51%, monocytes 93%, lymphs 64%, and eosinophils and basophils 30% and 18% respectively. Neutrophils increased 46% with exercise, (PreE 2878.5 + 1220.3, PostE 4058.7 + 1535.2). Higher PostE neutrophilia was associated with lower PreE neutrophils β= -0.41, higher PreE monocytes β=0.38, and greater body weight β=0.25 and duration of exercise β=0.19 (F=11.5, (4,95), p<.001). Gender, asthma, and fitness did not influence neutrophilia. Higher PreE neutrophils were associated with higher PreE leukocyte count (β=.903) increased age (β=.25), and less body wt (β=-.20, F=146.3, (3,99), p<.001). In conclusion, for both asthmatic and healthy children, pre-exercise leukocyte levels influence the acute immune response to short bouts of exercise. [ABSTRACT FROM AUTHOR]