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1.  Aspirin and Clopidogrel Alter Core Temperature and Skin Blood Flow during Heat Stress 
Antithrombotic therapy with oral aspirin or clopidogrel (PlavixR) is associated with an attenuated skin vasodilator response and a greater rate of rise in core temperature in healthy, middle-aged individuals during passive heating in a water perfused suit.
The present double-blind, crossover study examined the functional consequences of 7 days of low-dose aspirin (ASA, 81 mg/day) vs. clopidogrel (CLO, 75 mg/day) treatment in 14 healthy, middle-aged (50–65 yrs) men and women during passive heating in air (40 min at 30°C, 40% rh) followed by exercise (60% V̇O2peak).
Oral temperature (Tor) was measured in the antechamber (23.0 ± 0.1°C) before entering a warm environmental chamber. After 40 minutes of rest subjects cycled on a recumbent cycle ergometer for up to 120 minutes. Esophageal temperature (Tes) and laser Doppler flux were measured continuously, and the latter was normalized to maximal cutaneous vascular conductance (%CVCmax).
Prior to entry into the environmental chamber there were no differences in Tor among treatments; however, after 40 minutes of rest in the heat, Tes was significantly higher for ASA and CLO vs. placebo (37.2±0.1°C, 37.3±0.1°C, vs. 37.0±0.1°C, both P<0.001), a difference that persisted throughout exercise (P<0.001 vs. placebo). The mean body temperature thresholds for the onset of cutaneous vasodilation were shifted to the right for both ASA and CLO during exercise (P<0.05).
ASA and CLO resulted in elevated core temperatures during passive heat stress and shifted the onset of peripheral thermoeffector mechanisms toward higher body temperatures during exercise heat stress.
PMCID: PMC3594134  PMID: 23135368
acetylsalicylic acid; PlavixR; esophageal temperature; laser Doppler flowmetry
2.  Influence of diet, exercise and serum vitamin D on sarcopenia in post-menopausal women 
To investigate the effects of 12 months of dietary weight loss and/or aerobic exercise on lean mass and the measurements defining sarcopenia in postmenopausal women, and to examine the potential moderating effect of serum 25-hydroxyvitamin D (25(OH)D) and age.
439 overweight and obese postmenopausal women were randomized to: diet modification (N=118); exercise (N=117), diet+exercise (N=117), or control (N=87). The diet intervention was a group-based program with a 10% weight loss goal. The exercise intervention was 45 mins/day, 5 days/week of moderate-to-vigorous intensity aerobic activity. Total and appendicular lean mass were quantified by dual Xray absorptiometry (DXA) at baseline and 12 months. A skeletal muscle index (SMI=appendicular lean mass (kg)/m2) and the prevalence of sarcopenia (SMI<5.67 kg/m2) were calculated. Serum 25(OH)D was assayed using a competitive chemiluminescent immunoassay.
Dietary weight loss resulted in a significant decrease in lean mass, and a borderline significant decrease in appendicular lean mass and SMI compared to controls. In contrast, aerobic exercise significantly preserved appendicular lean mass and SMI. Diet + exercise attenuated the loss of appendicular lean mass and SMI compared to diet alone, and did not result in significant loss of total- or appendicular lean mass compared to controls. Neither serum 25(OH)D nor age were significant moderators of the intervention effects.
Aerobic exercise added to dietary weight loss can attenuate the loss of appendicular lean mass during weight loss, and may be effective for the prevention and treatment of sarcopenia among overweight and obese postmenopausal women.
PMCID: PMC3594522  PMID: 23190588
caloric restriction; weight loss; 25-hydroxyvitamin D; ageing
3.  Subconcussive Head Impact Biomechanics: Comparing Differing Offensive Schemes 
Recent literature suggests that sub-concussive impacts may influence cognitive functioning across the lifespan. These effects are suggested to manifest as functional and possibly structural changes. Head impact biomechanics during American football have been characterized from the high school to professional level, but style of play has not been considered.
The aim of this investigation was to quantify and compare head impact frequencies and magnitudes between two different offensive schemes.
We investigated the frequencies and magnitudes (linear acceleration [g], rotational acceleration [rad/s2], and HITsp) of head impacts sustained by 83 high school football athletes, playing for schools employing two different offensive schemes. The two schemes comprised of a run first offense (42 athletes) and a pass first offense (41 athletes). The Head Impact Telemetry System was used to record head impact measures.
A total of 35,620 impacts were recorded across two seasons. Athletes in the run first offense sustained an average of 456 head impacts per season (41 practices and 9 games) while the pass first offense athletes sustained an average of 304 head impacts per season (44 practices and 9 games). The pass first offense however sustained significantly higher impact magnitudes (p’s<0.05; 28.56g, 1777.58rad/s2, and 16.24) than the run first offense (25.67g, 1675.36rad/s2, and 15.48) across a season.
These data provide a first look at how different offensive strategies may influence head impact exposure in football athletes. In the study population, a run first offense was associated with more frequent head impacts, of smaller magnitude, than a pass first offense.
PMCID: PMC3605196  PMID: 23135370
4.  Physical Activity, Genes for Physical Fitness, and Risk of Coronary Heart Disease 
Both physical activity and physical fitness are associated with decreased coronary heart disease (CHD) risk. Our objective was to determine whether genes associated with physical fitness modify the association between physical activity and CHD.
We conducted a prospective cohort study among 23,016 initially healthy women in the Women’s Genome Health Study. Leisure-time physical activity was reported at entry and during follow-up. 58 single nucleotide polymorphisms associated with physical fitness were identified from published literature and summed to create four separate genetic scores related to phenotypes of endurance, muscle strength, VO2max, and overall fitness.
During a median of 14.4 years, 320 incident CHD events occurred. Increased physical activity was associated with lower CHD risk in multivariable-adjusted models (P = 0.0008). Independent of physical activity, only muscle strength genetic score was inversely associated with CHD risk (P = 0.05). There was no evidence that the inverse relation between physical activity and CHD was modified by any of the genetic scores for physical fitness. For overall fitness genetic score, the hazard ratio (HR) per 500 kcal/week of physical activity was 0.85 (95% CI: 0.72, 1.00) in the highest quartile of genetic score; 0.79 (95% CI: 0.67, 0.92) in the lowest quartile (P, interaction = 0.50). For VO2max genetic score, the HR was 0.86 (95% CI 0.72, 1.02) and 0.84 (95% CI 0.72, 0.98), respectively (P, interaction = 0.59).
In this large prospective cohort of women, genes associated with physical fitness did not modify the inverse association between physical activity and CHD risk.
PMCID: PMC3605203  PMID: 23073218
exercise; epidemiology; genetics; cardiovascular disease
5.  Head Impact Exposure Sustained by Football Players on Days of Diagnosed Concussion 
This study compares the frequency and severity of head impacts sustained by football players on days with and without diagnosed concussion and to identify the sensitivity and specificity of single impact severity measures to diagnosed injury.
1,208 players from eight collegiate and six high school football teams wore instrumented helmets to measure head impacts during all team sessions, of which 95 players were diagnosed with concussion. Eight players sustained two injuries and one three, providing 105 injury cases. Measures of head kinematics (peak linear and rotational acceleration, Gadd Severity Index (GSI), Head Injury Criteria (HIC15), change in head velocity (Δv)) and the number of head impacts sustained by individual players were compared between days with and without diagnosed concussion. Receiver operator characteristic curves were generated to evaluate the sensitivity and specificity of each kinematic measure to diagnosed concussion using only those impacts that directly preceded diagnosis.
Players sustained a higher frequency of impacts and impacts with more severe kinematic properties on days of diagnosed concussion than on days without diagnosed concussion. Forty-five injury cases were immediately diagnosed following head impact. For these cases, peak linear acceleration and HIC15 were most sensitive to immediately diagnosed concussion (AUC = 0.983). Peak rotational acceleration was less sensitive to diagnosed injury than all other kinematic measures (p = 0.01) which are derived from linear acceleration (peak linear, HIC15, GSI, and Δv).
Players sustain more impacts and impacts of higher severity on days of diagnosed concussion than on days without diagnosed concussion. Additionally, of historical measures of impact severity, those associated with peak linear acceleration are the best predictors of immediately diagnosed concussion.
PMCID: PMC3605215  PMID: 23135363
HIT System; Sport; impact biomechanics; MTBI; TBI; injury threshold
6.  Cardiorespiratory Fitness, Waist Circumference and Alanine Aminotransferase in Youth 
Non-alcoholic fatty liver disease (NAFLD) is considered the liver component of the metabolic syndrome and is strongly associated with cardiometabolic diseases. In adults, cardiorespiratory fitness (CRF) is inversely associated with alanine aminotransferase (ALT), a blood biomarker for NAFLD. However, information regarding these associations is scarce for youth.
To examine associations between CRF, waist circumference (WC) and ALT in youth.
Data were obtained from youth (n=2844, 12-19 years) in the National Health and Nutrition Examination Survey (NHANES) 2001-2004. CRF was dichotomized into youth FITNESSGRAM® categories of “low” and “adequate” CRF. Logistic and quantile regression were used for a comprehensive analysis of associations, and variables with previously-reported associations with ALT were a priori included in the models.
Results from logistic regression suggested that youth with low CRF had 1.5 times the odds of having an ALT>30 than youth with adequate CRF, although the association was not statistically significant (P=0.09). However, quantile regression demonstrated that youth with low CRF had statistically significantly higher ALT (+1.04, +1.05, and +2.57 U/L) at the upper end of the ALT distribution (80th, 85th, and 90th percentiles, respectively) than youth with adequate CRF. For every 1-cm increase in WC, the odds of having an ALT>30 increased by 1.06 (P<0.001), and the strength of this association increased across the ALT distribution.
Future studies should examine whether interventions to improve CRF can decrease hepatic fat and liver enzyme concentrations in youth with ALT ≥80th percentile or in youth diagnosed with NAFLD.
PMCID: PMC3605269  PMID: 23190589
Adolescents; Exercise; Metabolic Syndrome X; Non-alcoholic Fatty Liver Disease
7.  Timing of Concussion Diagnosis is Related to Head Impact Exposure Prior to Injury 
Concussions are commonly undiagnosed in an athletic environment because the post-injury signs and symptoms may be mild, masked by the subject, or unrecognized. This study compares measures of head impact frequency, location and kinematic response prior to cases of immediate and delayed concussion diagnosis.
Football players from eight collegiate and six high school teams wore instrumented helmets during play (n=1,208), of which ninety-five were diagnosed with concussion (105 total cases). Acceleration data recorded by the instrumented helmets was reduced to five kinematic metrics: peak linear and rotational acceleration, GSI, HIC15, and change in head velocity (Δv). Additionally, each impact was assigned to one of four general location regions (Front, Back, Side, and Top), and the number of impacts sustained prior to injury was calculated over two time periods (one and seven days).
All head kinematic measures associated with injury, except peak rotational acceleration (p = 0.284), were significantly higher for cases of immediate diagnosis than delayed diagnosis (p<0.05). Players with delayed diagnosis sustained a significantly higher number of head impacts on the day of injury (32.9 ±24.9; p < 0.001) and within seven days of injury (69.7 ±43.3; p = 0.006) than players with immediate diagnosis (16.5 ±15.1 and 50.2 ±43.6). Impacts associated with concussion occurred most frequently to the Front of the head (46%) followed by the Top (25%), Side (16%), and Back (13%) with the number of impacts by location independent of temporal diagnosis (χ2(3) = 4.72; p = 0.19).
Concussions diagnosed immediately after an impact event are associated with the highest kinematic measures, while those characterized by delayed diagnosis are preceded by a higher number of impacts.
PMCID: PMC3605273  PMID: 23135364
HIT System; impact biomechanics; MTBI; TBI; injury threshold; symptomatology
8.  Exercise-Induced Pain Requires NMDA Receptor Activation in the Medullary Raphe Nuclei 
Pain in response to physical activity is common in people with chronic musculoskeletal pain and is likely a barrier to regular exercise, which would lead to a sedentary lifestyle. We recently developed a model of exercise-induced pain that is associated with increased activation of neurons in the medullary raphe nuclei, i.e., the nucleus raphe obscurus (NRO) and nucleus raphe pallidus (NRP). Because the NRO and NRP not only modulate motor output but also respond to noxious stimuli, we hypothesized that the NRO and NRP were key nuclei in the interaction between pain and exercise. We tested whether exercise enhances hyperalgesia through activation of N-methyl D-aspartate (NMDA) receptors in the NRO/NRP.
Muscle insult was induced by two injections of pH 5.0 saline 5 d apart into one gastrocnemius muscle. We initially tested whether hyperalgesia developed in mice injected with acidic saline (pH 5.0) into the gastrocnemius muscle immediately after a 30-min or 2-h exercise task or 2 h after a 2-h exercise task. Next, we tested whether blockade of NMDA receptors in the NRO/NRP during the exercise task prevented the development of exercise-induced hyperalgesia. Finally, we evaluated changes in phosphorylation of the NR1 subunit of the NMDA receptor (pNR1) after the exercise task at times in which muscle insult was given in behavioral experiments, i.e., immediately after a 30-min or 2-h exercise task or 2 h after the 2-h exercise task.
All exercise conditions enhanced nociception (hyperalgesia) after combining with two injections of pH 5.0 saline. Microinjection of AP5 (1.0–0.1 nmol; 2-amino-5-phophonopenanoate) dose-dependently prevented the development of exercise-induced hyperalgesia. All exercise conditions increased pNR1 in the NRO and NRP.
Thus, exercise-induced pain in sedentary mice is associated with increased phosphorylation and activation of NMDA receptors in the NRO/NRP, suggesting that changes in central excitability mediate an interaction between unaccustomed exercise and pain.
PMCID: PMC3955196  PMID: 21795998
9.  Do Athletes Excel at Everyday Tasks? 
Cognitive enhancements are associated with sport training. We extended the sport-cognition literature by using a realistic street crossing task to examine the multitasking and processing speed abilities of collegiate athletes and nonathletes.
Pedestrians navigated trafficked roads by walking on a treadmill in a virtual world, a challenge that requires the quick and simultaneous processing of multiple streams of information.
Athletes had higher street crossing success rates than nonathletes, as reflected by fewer collisions with moving vehicles. Athletes also showed faster processing speed on a computer-based test of simple reaction time, and shorter reaction times were associated with higher street crossing success rates.
The results suggest that participation in athletics relates to superior street crossing multitasking abilities and that athlete and nonathlete differences in processing speed may underlie this difference. We suggest that cognitive skills trained in sport may transfer to performance on everyday fast-paced multitasking abilities.
PMCID: PMC3953501  PMID: 21407125
10.  Advances in Exercise, Fitness, and Performance Genomics in 2010 (Medicine and Science in Sports and Exercise) 
This review of the exercise genomics literature emphasizes the strongest papers published in 2010 as defined by sample size, quality of phenotype measurements, quality of the exercise program or physical activity exposure, study design, adjustment for multiple testing, quality of genotyping, and other related study characteristics. One study on voluntary running wheel behavior was performed in 448 mice from 41 inbred strains. Several quantitative trait loci for running distance, speed, and duration were identified. Several studies on the alpha-3 actinin (ACTN3) R577X nonsense polymorphism and the angiotensin converting enzyme (ACE) I/D polymorphism were reported with no clear evidence for a joint effect, but the studies were generally underpowered. Skeletal muscle RNA abundance at baseline for 29 transcripts and 11 single nucleotide polymorphisms (SNPs) were both found to be predictive of the VO2max response to exercise training in one report from multiple laboratories. None of the 50 loci associated with adiposity traits is known to influence physical activity behavior. However, physical activity appears to reduce the obesity-promoting effects of at least 12 of these loci. Evidence continues to be strong for a role of gene-exercise interaction effects on the improvement in insulin sensitivity following exposure to regular exercise. SNPs in the cAMP responsive element binding position 1 (CREB1) gene were associated with training-induced heart rate response, in the C-reactive protein (CRP) gene with training-induced changes in left ventricular mass, and in the methylenetetrahydrofolate reductase (MTHFR) gene with carotid stiffness in low-fit individuals. We conclude that progress is being made but that high-quality research designs and replication studies with large sample sizes are urgently needed.
PMCID: PMC3951763  PMID: 21499051
Genetics; exercise training; candidate genes; gene-exercise interaction; single nucleotide polymorphism; quantitative trait locus; genomic predictors
11.  Oxidative Stress and COPD: The Impact of Oral Antioxidants on Skeletal Muscle Fatigue 
Oxidative stress may contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). This study sought to determine the effect of an acute oral antioxidant cocktail (AOC: vitamins C, E, and alpha-lipoic acid) on skeletal muscle function during dynamic quadriceps exercise in COPD.
Ten patients with COPD performed knee extensor exercise to exhaustion and isotime trials following either the AOC or placebo (PL). Pre- to post-exercise changes in quadriceps maximal voluntary contractions (MVCs) and potentiated twitch forces (Qtw,pot) quantified quadriceps fatigue.
Under PL conditions, the plasma electron paramagnetic resonance (EPR) spectroscopy signal was inversely correlated with the forced expiratory volume in one second to forced vital capacity ratio (FEV1/FVC), an index of lung dysfunction (r=−0.61, p=0.02), and MVC force (r=−0.56, p=0.04). AOC consumption increased plasma ascorbate levels (10.1±2.2 to 24.1±3.8 ug/ml, p<0.05) and attenuated the area under the curve of the EPR spectroscopy free radical signal (11.6±3.7 to 4.8±2.2 AU, p<0.05), but did not alter endurance time or quadriceps fatigue. The ability of the AOC to decrease the EPR spectroscopy signal, however, was prominent in those with high basal free radicals (n=5, PL: 19.7±5.8 to AOC: 5.8±4.5 AU, p<0.05) with minimal effects in those with low levels (n=5, PL: 1.6±0.5 to AOC: 3.4±1.1 AU).
These data document a relationship between directly measured free radicals and lung dysfunction, and the ability of the AOC to decrease oxidative stress in COPD. Acute amelioration of free radicals, however, does not appear to impact dynamic quadriceps exercise performance.
PMCID: PMC3947987  PMID: 23299763
Free radicals; electron paramagnetic resonance spectroscopy; peripheral fatigue; knee extensor
12.  Hamstring Strength and Morphology Progression after Return to Sport from Injury 
Hamstring strain re-injury rates can reach 30% within the initial two weeks following return to sport (RTS). Incomplete recovery of strength may be a contributing factor. However, relative strength of the injured and unaffected limbs at RTS is currently unknown. PURPOSE: Characterize hamstring strength and morphology at the time of RTS and six months later. METHODS: Twenty-five athletes that experienced an acute hamstring strain injury participated, following completion of a controlled rehabilitation program. Bilateral isokinetic strength testing and magnetic resonance imaging (MRI) were performed at RTS and 6-months later. Strength (knee flexion peak torque, work, angle of peak torque) and MRI (muscle and tendon volumes) measures were compared between limbs and over time using repeated measures ANOVA. RESULTS: The injured limb showed a peak torque deficit of 9.6% compared to the uninjured limb at RTS (60°/s, p<0.001), but not 6-months following. The knee flexion angle of peak torque decreased over time for both limbs (60°/s, p<0.001). MRI revealed that 20.4% of the muscle cross-sectional area showed signs of edema at RTS with full resolution by the 6-month follow-up. Tendon volume of the injured limb tended to increase over time (p=0.108), while muscle volume decreased 4–5% in both limbs (p<0.001). CONCLUSION: Residual edema and deficits in isokinetic knee flexion strength were present at RTS, but resolved during the subsequent six months. This occurred despite MRI evidence of scar tissue formation (increased tendon volume) and muscle atrophy, suggesting that neuromuscular factors may contribute to the return of strength.
PMCID: PMC3580023  PMID: 23059864
magnetic resonance imaging; knee flexion torque; rehabilitation; muscle volume
13.  Acute effects of exercise and calorie restriction on triglyceride metabolism in women 
The mechanisms by which exercise reduces fasting plasma triglyceride (TG) concentrations in women and the effect of negative energy balance independent of muscular contraction are not known.
The aim of this study was to evaluate the effects of equivalent energy deficits induced by exercise or calorie restriction on basal very low-density lipoprotein (VLDL) TG metabolism in women.
Eleven healthy women (age: 23.5±2.7 years, BMI: 21.6±1.4 kg/m2) underwent a stable isotopically labeled tracer infusion study to determine basal VLDL-TG kinetics after performing, in random order, three experimental trials on the previous day: i) a single exercise bout (brisk walking at 60% of peak oxygen consumption for 123±18 min, with a net energy expenditure of 2.06±0.39 MJ (~500 kcal)), ii) dietary energy restriction of 2.10±0.41 MJ, and iii) a control day of isocaloric feeding and rest (zero energy balance).
Fasting plasma VLDL-TG concentration was ~30% lower after the exercise trial compared to the control trial (P<0.001), whereas no significant change was detected after the calorie restriction trial (P=0.297 vs control). Relative to the control condition, exercise increased the plasma clearance rate of VLDL-TG by 22% (P=0.001) and reduced hepatic VLDL-TG secretion rate by ~17% (P=0.042), whereas hypocaloric diet had no effect on VLDL-TG kinetics (P>0.2).
(i) Exercise-induced hypotriglyceridemia in women manifests through a different mechanism (increased clearance and decreased secretion of VLDL-TG) than that previously described in men (increased clearance of VLDL-TG only), and (ii) exercise affects TG homeostasis by eliciting changes in VLDL-TG kinetics that cannot be reproduced by an equivalent diet-induced energy deficit, indicating that these changes are independent of the exercise-induced negative energy balance but instead are specific to muscular contraction.
PMCID: PMC3660976  PMID: 23073216
physical activity; hypocaloric diet; triacylglycerol; hypotriglyceridemia
US high school athletes sustain millions of injuries annually. Detailed patterns of knee injuries, among the most costly sports injuries, remain largely unknown. We hypothesize that patterns of knee injuries in US high school sports differ by sport and gender.
US High school sports-related injury data were collected for 20 sports using the National High School Sports-Related Injury Surveillance System, High School RIO™. Knee injury rates, rate ratios, and injury proportion ratios were calculated.
From 2005/06–2010/11, 5,116 knee injuries occurred during 17,172,376 athlete exposures (AEs) for an overall rate of 2.98 knee injuries per 10,000 AEs. Knee injuries were more common in competition than practice (RR 3.53, 95% CI 3.34–3.73). Football had the highest knee injury rate (6.29 per 10,000 AEs) followed by girls’ soccer (4.53) and girls’ gymnastics (4.23). Girls had significantly higher knee injury rates than boys in gender-comparable sports (soccer, volleyball, basketball, baseball/softball, lacrosse, swimming and diving, and track and field) (RR 1.52, 95% CI 1.39–1.65). The most commonly involved structure was the MCL (reported in 36.1% of knee injuries), followed by the patella/patellar tendon (29.5%), ACL (25.4%), meniscus (23.0%), LCL (7.9%), and PCL (2.4%). Girls were significantly more likely to sustain ACL injuries in gender-comparable sports (RR 2.38, 95% CI 1.91–2.95). Overall, 21.2% of knee injuries were treated with surgery; girls were more often treated with surgery than boys in gender-comparable sports (IPR 1.30, 95% CI 1.11–1.53).
Knee injury patterns differ by sport and gender. Continuing efforts to develop preventive interventions could reduce the burden of these injuries.
PMCID: PMC3768257  PMID: 23059869
sports; surveillance; meniscus; ACL
15.  Prospective BMI category change associated with cardiovascular fitness change 
Test the relationship of change in body mass index (BMI) percentile score group (from 6th to 8th grade) with change in cardiovascular fitness (CVF), baseline BMIz-score and CVF.
3,998 (92%) children in the HEALTHY trial provided complete data at the beginning of 6th and end of 8th grades. Height and weight were assessed according to standardized protocol. CVF was measured using the 20 meter shuttle run. Changes in BMI percentile were categorized into five groups: increased a BMI category, stayed obese, stayed overweight, stayed healthy weight, and decreased a BMI category. Data were analyzed separately by gender, controlling for race, parental education, change in pubertal stage, and baseline BMIz-score and CVF.
Youth (males and females) who lowered their BMI group or remained in the healthy or overweight groups had significantly larger increases in CVF, than the stayed obese or increased a BMI category groups. But these relationships accounted for a small percentage of variance (i.e. weak relationship). Staying obese was associated with the highest baseline BMIz-score, with the second highest among those who decreased a BMI category. BMI category change accounted for the most variance in baseline BMIz-score.
Changes in BMI categories were substantially more strongly related to 6th grade values of BMIz-score than to CVF changes. Since pre-existing adiposity may inhibit adiposity change, changes in CVF and adiposity should be attempted prior to middle school.
PMCID: PMC3552042  PMID: 22935738
Obesity; Overweight; Longitudinal; Children
16.  Cardiorespiratory Fitness as a Predictor of Dementia Mortality in Men and Women 
There is evidence that physical activity may reduce the risk of developing Alzheimer’s disease and dementia. However, few reports have examined the physical activity-dementia association with objective measures of physical activity. Cardiorespiratory fitness (hereafter called fitness) is an objective reproducible measure of recent physical activity habits.
We sought to determine whether fitness is associated with lower risk for dementia mortality in women and men.
We followed 14,811 women and 45,078 men, ages 20-88 at baseline, for an average of 17 years. All participants completed a preventive health examination at the Cooper Clinic in Dallas, Texas during 1970-2001. Fitness was measured with a maximal treadmill exercise test, with results expressed in maximal metabolic equivalents (METs). The National Death Index identified deaths through 2003. Cox proportional hazards models were used to examine the association between baseline fitness and dementia mortality, adjusting for age, sex, examination year, body mass index, smoking, alcohol use, abnormal ECGs, and health status.
There were 164 deaths with dementia listed as the cause during 1,012,125 person-years of exposure. Each 1-MET increase in fitness was associated with a 14% lower adjusted risk of dementia mortality (95% confidence interval, CI 6%-22%). With fitness expressed in tertiles, adjusted hazard ratios (HRs) for those in the middle and high fitness groups suggest their risk of dementia mortality was less than half that of those in the lowest fitness group (respectively: HR 0.44, CI 0.26-0.74; HR 0.49, CI 0.26-0.90).
Greater fitness was associated with lower risk of mortality from dementia in a large cohort of men and women.
PMCID: PMC3908779  PMID: 21796048
physical fitness; cognitive function; Alzheimer’s disease; vascular dementia; metabolic equivalents (METs)
17.  Monthly Variation in Physical Activity Levels in Post-Menopausal Women 
Medicine and science in sports and exercise  2009;41(2):10.1249/MSS.0b013e3181864c05.
Month-to-month variation in physical activity levels in a cohort of post-menopausal women participating in a single site clinical trial undergoing lifestyle intervention was investigated prior to and after lifestyle intervention.
Participants were Caucasian and African-American women (mean age 57.0 ± 3.0) from the Women On the Move through Activity and Nutrition (WOMAN) study. Physical activity was measured subjectively by questionnaire and objectively by pedometer at baseline and at the 18-month follow-up.
At baseline, prior to intervention, pedometer steps were highest in the summer months (7,616 steps/day), lower in the fall (6,293 steps/day), lowest in winter (5,304 steps/day), and then rebounded in the spring (5,850 steps/day). Physical activity estimates from the past-week subjective measure followed the same seasonal pattern. After 18-months, the lifestyle change group significantly increased their pedometer step counts when compared to the health education group (p<0.0001). At 18-months, pedometer step counts for the health education group followed a pattern similar to that found in the entire group prior to intervention, whereas, month-to-month step counts for the lifestyle change group appeared to remain consistent throughout the year.
These results confirm previous reports that suggest physical activity levels fluctuate throughout the year. Lifestyle intervention, which includes a physical activity component, not only increases step counts, but appears to reduce some of variation in physical activity levels over the course of a year in post-menopausal women.
PMCID: PMC3880933  PMID: 19127194
pedometer; seasonality; post-menopause; lifestyle intervention
To compare daily ambulatory measures in children, adolescents, and young adults with and without metabolic syndrome, and to assess which metabolic syndrome components, demographic measures, and body composition measures are associated with daily ambulatory measures.
Two-hundred fifty subjects between the ages of 10 and 30 years were assessed on metabolic syndrome components, demographic and clinical measures, body fat percentage, and daily ambulatory strides, durations, and cadences during seven consecutive days. Forty-five of the 250 subjects had metabolic syndrome, as defined by the International Diabetes Federation.
Subjects with metabolic syndrome ambulated at a slower daily average cadence than those without metabolic syndrome (13.6 ± 2.2 strides/min vs. 14.9 ± 3.2 strides/min; p=0.012), and they had slower cadences for continuous durations of 60 minutes (p=0.006), 30 minutes (p=0.005), 20 minutes (p=0.003), 5 minutes (p=0.002), and 1 minute (p=0.001). However, the total amount of time spent ambulating each day was not different (p=0.077). After adjustment for metabolic syndrome status, average cadence is linearly associated with body fat percentage (p<0.001) and fat mass (p<0.01). Group difference in average cadence was no longer significant after adjusting for body fat percentage (p=0.683) and fat mass (p=0.973).
Children, adolescents, and young adults with metabolic syndrome ambulate more slowly and take fewer strides throughout the day than those without metabolic syndrome, even though the total amount of time spent ambulating is not different. Furthermore, the detrimental influence of metabolic syndrome on ambulatory cadence is primarily a function of body fatness.
PMCID: PMC3521853  PMID: 22811038
Ambulation; body fat; children; metabolic syndrome; physical activity
19.  25(OH) Vitamin D is Associated with Greater Muscle Strength in Healthy Men and Women 
The purpose of the study was to examine the relationship between serum 25-hydroxy vitamin D (25(OH)D) levels and muscle strength in 419 healthy men and women over a broad age range (20-76 years of age).
Isometric and isokinetic strength of the arms and legs was measured using computerized dynamometry and its relation to vitamin D was tested in multivariate models controlling for age, gender, resting heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), maximal oxygen uptake (VO2max,), physical activity counts, and season of vitamin D measurement.
Vitamin D was significantly associated with arm and leg muscle strength when controlling for age and gender. When controlling for other covariates listed above, vitamin D remained directly related to both isometric and isokinetic arm strength but only to isometric leg strength.
These data suggests that there may be a differential effect of vitamin D on upper and lower body strength. The mechanism for this difference remains unclear but could be related to differences in androgenic effects or to differences in vitamin D receptor expression. Our study supports a direct relationship between vitamin D and muscle strength and suggests that vitamin D supplementation be evaluated to determine if it is an effective therapy to preserve muscle strength in adults.
PMCID: PMC3544152  PMID: 22895376
25-Hydroxyvitamin D; Dynamometry; Androgen; VDR
20.  Metabolic Syndrome and Insulin Resistance in Division 1 Collegiate Football Players 
Medicine and science in sports and exercise  2009;41(12):10.1249/MSS.0b013e3181abdfec.
BORCHERS, J. R., K. L. CLEM, D. L. HABASH, H. N. NAGARAJA, L. M. STOKLEY, and T. M. BEST. Metabolic Syndrome and Insulin Resistance in Division 1 Collegiate Football Players. Med. Sci. Sports Exerc., Vol. 41, No. 12, pp. 2105–2110, 2009.
To estimate the prevalence of metabolic syndrome and insulin resistance in a cohort of Division 1 collegiate football players.
Ninety football players were evaluated in a cross-sectional study to estimate the prevalence of metabolic syndrome, insulin resistance, and associated risk factors. Obesity was defined as a body fat ≥25% determined by BOD POD measurements. The National Cholesterol Education Program Adult Treatment Panel III criteria were used to estimate prevalence of metabolic syndrome. Quantitative insulin sensitivity check index calculations were performed to estimate prevalence of insulin resistance. Linear regression techniques were used to determine association between body fat percentage and other measured continuous parameters. Fisher exact test was used to determine association between nominal variables, and one-way ANOVA compared the three groups defined by position.
Summary measures showed a small prevalence of abnormal individual measurements. There was an association between body fat percentage and most evaluated parameters (P < 0.05). The prevalence of obesity, insulin resistance, and metabolic syndrome was 21%, 21%, and 9%, respectively. Obesity is closely associated with metabolic syndrome (P < 0.0001) and insulin resistance (P < 0.0001) in this population. All subjects with metabolic syndrome were obese, and the odds for insulin resistance in the obese group are 10.6 times the odds for the nonobese group. Linemen (n = 29) had 19 of the 19 obese subjects, 13 of the 19 subjects with insulin resistance, and all subjects with metabolic syndrome.
There is a strong association between obesity and both metabolic syndrome and insulin resistance in Division 1 collegiate football players. Linemen are at significant risk for metabolic syndrome and insulin resistance compared with other positions. This may be predictive of future health problems in Division 1 collegiate football players, especially linemen.
PMCID: PMC3872996  PMID: 19915510
Obesity; Cardiovascular Risk Factors; Exercise; Diet
21.  A Yearlong Exercise Intervention Decreases CRP among Obese Postmenopausal Women 
Medicine and science in sports and exercise  2009;41(8):10.1249/MSS.0b013e31819c7feb.
To investigate the effect of a yearlong moderate-intensity aerobic exercise intervention on C-reactive protein (CRP), serum amyloid A (SAA), and interleukin 6 (IL-6) among overweight or obese postmenopausal women.
In a randomized controlled trial, 115 postmenopausal, overweight or obese, sedentary women, aged 50-75 years were randomized to an aerobic exercise intervention of moderate-intensity (60-75% observed maximal heart rate), for ≥45 min/day, 5 days/week (n=53), or to a 1 day/week stretching control (n=62), on an intent-to-treat basis. CRP, SAA, and IL-6 were measured at baseline, 3-months, and 12-months.
From baseline to 12-months, CRP decreased 10% in exercisers and increased 12% in controls (p=0.01); no effects were observed for SAA and IL-6. Among participants at baseline who were obese (BMI≥30kg/m2) or had abdominal obesity (waist circumference (WC)≥88cm), exercise resulted in a more pronounced reduction in CRP (BMI≥30kg/m2: p=0.002; WC≥88cm: p<0.0001), borderline for SAA (BMI≥30kg/m2: p=0.08; WC≥88cm: p=0.04); no intervention effects were observed among women who did not have these characteristics. Overall, weight loss was minimal in the exercise intervention (~1.8kg). Linear trends were observed between CRP and 12-month changes in: aerobic fitness (ptrend = 0.006), exercise adherence (ptrend = 0.004), percentage body fat (ptrend = 0.002), body weight (ptrend = 0.002), waist circumference (ptrend = 0.02), and intra-abdominal fat (ptrend = 0.03).
A moderate-intensity exercise intervention reduced CRP over 12-months among women who were obese at baseline. These findings support the role of exercise in modulating inflammatory processes that are related to increased risk of chronic disease among obese women.
PMCID: PMC3850754  PMID: 19568208
overweight; inflammation; C-reactive protein; physical activity; randomized controlled trial; serum amyloid A
22.  Genetic Variation of SCNN1A Influences Lung Diffusing Capacity in Cystic Fibrosis 
Epithelial Na+ Channels (ENaC) play a crucial role in ion and fluid regulation in the lung. In cystic fibrosis (CF) Na+ hyperabsorption results from ENaC over activity, leading to airway dehydration. Previous work has demonstrated functional genetic variation of SCNN1A (the gene encoding the ENaC α-subunit), manifesting as an alanine (A) to threonine (T) substitution at amino acid 663, with the αT663 variant resulting in a more active channel.
We assessed the influence of genetic variation of SCNN1A on the diffusing capacity of the lungs for carbon monoxide (DLCO) and nitric oxide (DLNO), together with alveolar capillary membrane conductance (DM), pulmonary capillary blood volume (VC), and alveolar volume (VA) at rest and during peak exercise in 18 patients with CF [10 homozygous for αA663 (AA group) and 8 with at least one T663 allele (AT/TT group)]. Due to the more active channel we hypothesized that the AT/TT group would show a greater increase in DLCO, DLNO, and DM with exercise due to exercise-mediated ENaC inhibition and subsequent attenuation of Na+ hyperabsorption.
The AT/TT group had significantly lower pulmonary function, weight and BMI than the AA group. Both groups had similar peak workloads, relative peak oxygen consumptions, and cardiopulmonary responses to exercise. The AT/TT group demonstrated a greater increase in DLNO, DLNO/VA, and DM in response to exercise (% increases: DLNO= 18±11vs.41±38; DLNO/VA= 14±21vs.40±37; DM= 15±11vs.41±38, AAvs.AT/TT, respectively). There were no differences between groups in absolute diffusing capacity measures at peak exercise.
These results suggest that genetic variation of the alpha-subunit of ENaC differentially affects the diffusing capacity response to exercise in patients with CF.
PMCID: PMC3501594  PMID: 22776878
exercise; cystic fibrosis; diffusing capacity; DLNO; DLCO; ENaC polymorphism
23.  Effect of BMI on prediction of accelerometry-based energy expenditure in youth 
To determine the effect of body mass index (BMI) on level of agreement between six previously established prediction equations for three commonly used accelerometers to predict summary measures of energy expenditure (EE) in youth.
One hundred thirty-one youth between the ages of 10–17 years and BMI from 15 to 44 kg/m2 were outfitted with hip-worn ActiGraph GT1M, Actical, and RT3 accelerometers and spent approximately 24 hours in a whole-room indirect calorimeter while performing structured and self-selected activities. Five commonly used regression and one propriety equations for each device were used to predict the minute-to-minute EE (normalized to metabolic equivalents, METs), daily physical activity level (PAL), and time spent in sedentary, light, moderate, and vigorous physical activity intensity categories. The calculated values were compared with criterion measurements obtained from the room calorimeter.
All predictive equations, except RT3, significantly over- or under-predicted daily PAL (p < 0.001), with large discrepancies observed in the estimate of sedentary and light activity. Discrepancies between actual and estimated PAL ranged from 0.05 to 0.68. In addition, BMI represented a modifier for two ActiGraph predictive equations (AG1 and AG2), affecting the accuracy of physical activity-related EE (PAEE) predictions.
ActiGraph (AG3) and the RT3 closely predicted overall PAL (within 4.2 and 6.8%, respectively) as a group. When adjusting for age, sex, and ethnicity, Actical (AC1 and AC2) and ActiGraph (AG3) were not influenced by BMI. However, a gap between some hip-worn accelerometer predictive and regression equations was demonstrated compared to both criterion measurement and each other, which poses a potential difficulty for inter-study (e.g. different accelerometers) and intra-study (e.g., BMI, adiposity) comparisons.
PMCID: PMC3501581  PMID: 22776880
Energy prediction; Adiposity; Actical; ActiGraph; RT3
24.  Expiratory Loading Improves Cardiac Output During Exercise In Heart Failure 
To investigate the effect of changes in expiratory intrathoracic pressure (ITP) on stroke volume (SV) at rest and during moderate exercise in patients with heart failure vs. healthy individuals.
SV was obtained by echocardiography during spontaneous breathing and during expiratory loads of 5 and 10 cm H2O produced by a ventilator in 11 patients with heart failure (61±9 years, EF: 32±4%, NYHA class I-II) and 11 age-matched healthy individuals at rest and during exercise at 60% of aerobic capacity on a semi-recumbent cycle ergometer.
At rest, expiratory loading did not change heart rate, SV index (SVI) or cardiac index (CI) in either group. During moderate exercise, expiratory loading increased SVI and CI in patients with heart failure, but decreased SVI and CI in healthy individuals. There was a negative correlation between changes in gastric pressure and SVI (r=−0.51, p<0.05) in healthy individuals, while there was a positive correlation between changes in gastric pressure accompanying expiratory loading and CI (r=0.83, p<0.01) in patients with heart failure.
Expiratory loading during moderate exercise elicited increases in SVI and CI in patients with heart failure but decreased SVI and CI in healthy individuals. Improvements in cardiac function during submaximal exercise in patients with heart failure may be caused by a beneficial reduction in LV preload.
PMCID: PMC3501573  PMID: 22776881
preload; cardiorespiratory; exercise tolerance; stroke volume
25.  Environmental And Psychological Correlates of Older Adult’s Active Commuting 
Medicine and science in sports and exercise  2011;43(7):10.1249/MSS.0b013e3182078532.
This study explored the environmental and psychological correlates of active commuting in a sample of adults from the European Prospective Investigation into Cancer (EPIC) Norfolk cohort.
Members of the cohort who were in employment, lived within 10km of work, and did not report a limitation that precluded walking were included in this analysis. Psychological factors, perceptions of the neighbourhood environment and travel mode to work were reported using questionnaires. Neighbourhood and route environmental characteristics were estimated objectively using a Geographical Information System. The mediating effects of psychological factors were assessed using a series of regression models.
1279 adults (mean age of 60.4 years SD=5.4) were included in this analysis, of which, 25% actively commuted to work. In multivariable regression analyses, those who reported strong habits for walking or cycling were more likely to actively commute, whilst those living 4-10km from work were less likely to actively commute. In addition, living in a rural area was associated with a decreased likelihood of men’s active commuting and in women, living in a neighbourhood with high road density and having a route to work which was not on a main or secondary road was associated with an increased likelihood of active commuting. There was weak evidence that habit acted to partly mediate the associations between environmental correlates and active commuting in both sexes.
The findings suggest that interventions designed to encourage the development of habitual behaviours for active commuting may be effective, especially amongst those living close to work.
PMCID: PMC3842528  PMID: 21131863
walking; cycling; EPIC-Norfolk; neighbourhood; route

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