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1.  Cardiorespiratory Characteristics and Cholesterol Responses to a Single Session of Heavy Leg Press Exercise 
The effect of resistance exercise on blood lipids is not clear yet. The purpose of this study was to examine the cholesterol responses to a heavy resistance leg press exercise emphasizing on the eccentric movement 24 and 48 hours following exercise and to quantify the cardiorespiratory responses of the exercise bout in an attempt to clarify the exercise characteristics that may be responsible for the effects of heavy resistance exercise on blood lipids. Nine healthy, untrained male volunteers aged 27.2 ± 1.1 yrs (76.2 ± 2.5 kg, 1.79 ± 0.02 m) performed a session of heavy RE emphasizing on the eccentric movement consisting of eight sets of inclined leg presses at six repetition maximum with 3-min rest intervals. Venous blood samples were obtained at rest (control) and 24 and 48 hours following exercise. Average VO2 at rest was 4.0 ± 0.4 ml·min−1·kg−1, during exercise 19.6 ± 0.2 ml·min−1·kg−1 and during the 180 sec recovery period between sets 12.5 ± 0.2 ml·min−1·kg−1. RER values decreased with the progression of the exercise and were significantly lower during the last four sets compared with the first four sets of the exercise session. Resting heart rate was 67 ± 2 bpm, and maximum heart rate during exercise was 168 ± 1 bpm. Serum creatine kinase was significantly elevated on day 1 (1090 ± 272 U·L−1, p < 0.03) and peaked on day 2 (1230 ± 440 U·L−1 p < 0. 01). Total cholesterol, HDL cholesterol and calculated LDL cholesterol concentration did not change significantly following with exercise. This protocol of heavy resistance exercise has no effect on TC or cholesterol sub-fraction concentration 24 and 48 hours following exercise which may be due to the low energy expenditure of the exercise and/or to the gender of the participants.
Key pointsRepeated sets of heavy resistance exercise significantly increase oxygen uptake both during exercise and the following recovery period.Even though exercise was of low volume (8 sets x 6 repetitions) the elevated oxygen uptake during the rest intervals in combination with the total exercise session duration (26 min) resulted in aerobic energy expenditure that is equivalent to low to moderate intensity cycling.Leg press resistance exercise emphasizing on the eccentric movement that caused muscle damage had no effect on total cholesterol, HDL-C and LDL-C during the two days following exercise in young healthy male subjects.
PMCID: PMC3761812  PMID: 24149784
Muscle damage; energy expenditure; total cholesterol; HDL; oxygen uptake.
2.  Peak Fat Oxidation Rate During Walking in Sedentary Overweight Men and Women 
The aim of this study was to determine the relative exercise intensity that elicits maximal fat oxidation during walking in inactive and overweight men and women and evaluate any possible sex differences. Forty six healthy, sedentary, overweight men (age: 36.3 ± 1.3 years, body fat: 28.8 ± 0.8%, n = 28, mean ± SE) and women (age: 36.6 ± 1.8 years, body fat: 37.1 ± 0.8%, n = 18) participated in the study. Fat oxidation was calculated from expired air analysis using indirect calorimetry during an incremental treadmill walking test. Peak fat oxidation rate (PFO) was higher in men compared to women (0.31 ± 0.02 vs. 0.20 ± 0.02 g.min-1; p < 0.001), but this difference disappeared when PFO was scaled per kg fat-free mass (4. 36 ± 0.23 vs. 3.99 ± 0.37 fat free mass-1.min-1). Also, the relative exercise intensity at which PFO occurred was similar for men and women and corresponded to 40.1 ± 1.8 and 39. 5 ± 2.3% of maximal oxygen uptake (VO2max) and 60.0 ± 1.4 and 57.8 ± 1.4% of maximal heart rate, respectively. The walking speed corresponding to PFO was 5.5 ± 0.2 and 5.0 ± 0.1 km·h-1 for men and women, respectively. Regression analysis showed that sex, FFM and VO2max were significant predictors of PFO expressed in g.min-1 (adjusted R2 = 0.48, p = 0.01). However when PFO was scaled per kg FFM, only a small part of the variance was explained by VO2max (adjusted R2 = 0.12, p < 0.05). In conclusion, peak fat oxidation rate and the corresponding relative exercise intensity were similar in male and female overweight and sedentary individuals, but lower compared to those reported for leaner and/or physically active persons. Walking at a moderate speed (5.0-5.5 km·h-1) may be used as a convenient way to exercise at an intensity eliciting peak fat oxidation in overweight individuals.
Key pointsPeak fat oxidation rate scaled per kg fat-free mass and the corresponding relative exercise intensity are similar in male and female overweight and sedentary individuals, but lower compared to those reported for leaner and/or physically active persons.Walking at a moderate speed (5.0-5.5 km.h-1) may be used as a convenient way to exercise at an intensity eliciting peak fat oxidation in overweight individuals.The relationship between %HRmax and %VO2max in overweight individuals is different from that reported for normal-weight adults and should be taken into account to optimize exercise intensity using heart rate in obese individuals.Due to the low intensity corresponding to peak fat oxidation in overweight and sedentary persons and the inter-individual differences, exercise intensity for health benefits should be prescribed following individual testing.
PMCID: PMC3761910  PMID: 24149961
Exercise intensity; calorimetry; substrate utilisation
3.  How to Regulate the Acute Physiological Response to “Aerobic” High-Intensity Interval Exercise 
The acute physiological processes during “aerobic” high-intensity interval exercise (HIIE) and their regulation are inadequately studied. The main goal of this study was to investigate the acute metabolic and cardiorespiratory response to long and short HIIE compared to continuous exercise (CE) as well as its regulation and predictability. Six healthy well-trained sport students (5 males, 1 female; age: 25.7 ± 3.1 years; height: 1.80 ± 0.04 m; weight: 76.7 ± 6.4 kg; VO2max: 4.33 ± 0.7 l·min-1) performed a maximal incremental exercise test (IET) and subsequently three different exercise sessions matched for mean load (Pmean) and exercise duration (28 min): 1) long HIIE with submaximal peak workloads (Ppeak = power output at 95 % of maximum heart rate), peak workload durations (tpeak) of 4 min, and recovery durations (trec) of 3 min, 2) short HIIE with Ppeak according to the maximum power output (Pmax) from IET, tpeak of 20 s, and individually calculated trec (26.7 ± 13.4 s), and 3) CE with a target workload (Ptarget) equating to Pmean of HIIE. In short HIIE, mean lactate (Lamean) (5.22 ± 1.41 mmol·l-1), peak La (7.14 ± 2.48 mmol·l-1), and peak heart rate (HRpeak) (181.00 ± 6.66 b·min-1) were significantly lower compared to long HIIE (Lamean: 9.83 ± 2.78 mmol·l-1; Lapeak: 12.37 ± 4.17 mmol·l-1, HRpeak: 187.67 ± 5.72 b·min-1). No significant differences in any parameters were found between short HIIE and CE despite considerably higher peak workloads in short HIIE. The acute metabolic and peak cardiorespiratory demand during “aerobic” short HIIE was significantly lower compared to long HIIE and regulable via Pmean. Consequently, short HIIE allows a consciously aimed triggering of specific and desired or required acute physiological responses.
Key pointsHigh-intensity interval exercise (HIIE) with short peak workload durations (tpeak) induce a lower acute metabolic and peak cardiorespiratory response compared to intervals with long tpeak despite higher peak workload intensities (Ppeak) and identical mean load (Pmean).Short HIIE response is the same as in continuous exercise (CE) matched for Pmean.It is possible to regulate and predict the acute physiological response by means of Pmean for short HIIE but not for long HIIE.The use of fixed percentages of maximal heart rate (HRmax) for exercise intensity prescription yields heterogeneous exercise stimuli across subjects. Therefore, objective individual markers such as the first and the second lactate turn point are recommend prescribing exercise intensity not only for continuous but also for intermittent exercise.
PMCID: PMC4306779  PMID: 25729286
Intermittent exercise; exercise prescription; acute physiological demand; mean load; peak workload duration
4.  Gender differences in injuries among rural youth. 
Injury Prevention  1995;1(1):15-20.
GOAL: This paper presents injury data from the first year of a three year longitudinal study of risk taking behaviors among adolescents. SAMPLE: Study subjects were a cohort of 758 rural students from Maryland's Eastern Shore who were in the eighth grade in 1987. METHODS: Students completed a 45 minute, self administered survey in which they reported numbers of injuries experienced in the past year, risk taking behaviors, anger expression, delinquency, alcohol and drug use, physical exercise, work experience, and level of parental supervision. In addition, students had their height and weight measurements taken by trained research staff and completed a self rating of pubertal development using Tanner drawings. RESULTS: Slightly more than half (53.2%) of the boys and over one third (37.7%) of the girls reported experiencing one or more medically attended injuries during the last year. Poisson regression analyses were conducted to estimate the extent to which gender differences in injuries could be accounted for by adolescent behaviors. Gender effects became non-significant when adjustments were made for risk taking, school discipline problems, and exercise frequency. Gender differences in injuries were reduced but remained significant when substance use, employment, and anger were controlled. Poisson regression analyses were conducted separately for males and females to assess whether factors associated with injuries were similar across genders. For boys, risk taking, anger, and school discipline problems were significantly related to number of injuries. Boys with a low body mass index and late pubertal development (mean ratio 3.09), as well as those with high body mass index and early pubertal development (mean ratio 2.16), reported greater numbers of injuries than average boys. For girls, substance use, cruising, risk taking, anger, and exercise frequency were significantly associated with injuries. Girls with an early onset of menses reported, on average, twice the number of injuries than those who were on time. Girls with high body mass index who were late in their pubertal development reported, on average, five times more injuries than other girls. CONCLUSIONS: Although gender is a significant risk factor for injuries, certain behaviors like risk taking, school related delinquency, and physical exercise partially explain the higher number of injuries among adolescent males in this study. For both males and females, indicators of pubertal and physical development are important factors to consider in studies of injuries during early adolescence.
PMCID: PMC1067535  PMID: 9345987
5.  Ventilatory response to exercise in adolescents with cystic fibrosis and mild-to-moderate airway obstruction 
SpringerPlus  2014;3:696.
Data regarding the ventilatory response to exercise in adolescents with mild-to-moderate cystic fibrosis (CF) are equivocal. This study aimed to describe the ventilatory response during a progressive cardiopulmonary exercise test (CPET) up to maximal exertion, as well as to assess the adequacy of the ventilatory response for carbon dioxide (CO2) exhalation. Twenty-two adolescents with CF (12 boys and 10 girls; mean ± SD age: 14.3 ± 1.3 years; FEV1: 78.6 ± 17.3% of predicted) performed a maximal CPET. For each patient, data of a sex- and age matched healthy control was included (12 boys and 10 girls; mean ± SD age: 14.3 ± 1.4 years). At different relative exercise intensities of 25%, 50%, 75%, and 100% of peak oxygen uptake (VO2peak), breathing pattern, estimated ventilatory dead space ventilation (VD/VT ratio), minute ventilation (VE) to CO2 production relationship (VE/VCO2-slope), partial end-tidal CO2 tension (PETCO2), and the VE to the work rate (VE/WR) ratio were examined. VO2peak was significantly reduced in CF patients (P = 0.01). We found no differences in breathing pattern between both groups, except for a significantly higher VE at rest and a trend towards a lower VE at peak exercise in patients with CF. Significantly higher values were found for the estimated VD/VT ratio throughout the CPET in CF patients (P < 0.01). VE/VCO2-slope and PETCO2 values differed not between the two groups throughout the CPET. VE/WR ratio values were significantly higher in CF during the entire range of the CPET (P < 0.01). This study found an exaggerated ventilatory response (high VE/WR ratio values), which was adequate for CO2 exhalation (normal VE/VCO2-slope and PETCO2 values) during progressive exercise up to maximal exhaustion in CF patients with mild-to-moderate airway obstruction.
PMCID: PMC4254890  PMID: 25512888
Pulmonary physiology; Ventilation; Breathing pattern; Children
6.  The Effect of High Intensity Interval Exercise in High / Low Temperatures on Exercise-Induced Bronchoconstriction (EIB) in Trained Adolescent Males 
Tanaffos  2013;12(3):29-43.
Exercise-induced bronchoconstriction (EIB) describes airway narrowing that occurs in association with exercise. Exercise in hot and cold environments has been reported to increase exercise-induced bronchoconstriction (EIB) in subjects with asthma. However, to our knowledge, the effect of hot and cold environment on pulmonary function and EIB in trained males has not been previously studied. The main goal of this research was to examine the influence of environmental temperature and high intensity interval exercise on pulmonary function in trained teenage males. Also, this study sought to assess the influence of exercise and environmental temperature on EIB.
Materials and Methods
Thirty trained subjects (mean age 16.56±0.89 yrs, all males) underwent high intensity interval exercise testing (22 minutes) by running on a treadmill in hot and cold environments under standardized conditions (10 °C and 45 °C with almost 50% relative humidity in random order in winter and summer). Lung function (flow volume loops) was measured before and 1, 5, 15, 30 and 60 min after the exercise by digital spirometer. Data was analyzed using SPSS software and P < 0.05 was considered significant. The diagnosis of EIB was made by 10% fall in FEV1 post-exercise.
The post-exercise maximal reduction in forced expiratory volume in 1s (FEV1), peak expiratory flow (PEF) and average forced expiratory flow rate over the middle 50% of the FVC (FEF25-75) increased significantly compared to pre-exercise at 10 °C with almost 50% relative humidity (cold air). The obtained values were: -15.93(15min post-exercise), -22.53 (1 min post-exercise) and -18.25%(5min post-exercise). Post-exercise maximal reduction in FEV1, PEF and FEF25-75 increased significantly compared to pre-exercise value at 45 °C with almost 50% relative humidity (hot air). Obtained values were: -10.35 (1 min post-exercise), -9.16 (1 min post-exercise) and -7.39 (5 min post-exercise). Changes in FEV1, PEF and FEF25-75 reduction in cold air was significantly greater than in hot air (P < 0.05). Maximal prevalence of exercise-induced bronchoconstriction (EIB) in cold and hot air was 60% (18 of 30 subjects) and 40% (12 of 30 subjects), respectively.
This study demonstrated that pulmonary function in hot and cold air was influenced by temperature (in the same relative humidity (50%) and also high intensity interval exercise. Prevalence of EIB after high intensity exercise in hot and cold air increased in trained adolescent males; however, these changes in cold air were greater than in hot air among trained adolescent males. Therefore, results of this study suggest that adolescents (although trained) should avoid high intensity (95% maximal heart rate) exercise in winter (extremely low temperature) and summer (extremely high temperature) to prevent EIB.
PMCID: PMC4153253  PMID: 25191471
Temperature; Exercise-Induced Bronchoconstriction; Exercise
7.  Abnormal haemodynamic response to exercise in heart failure with preserved ejection fraction 
European Journal of Heart Failure  2011;13(12):1296-1304.
Peak oxygen uptake (VO2) is diminished in patients with heart failure with preserved ejection fraction (HFpEF) suggesting impaired cardiac reserve. To test this hypothesis, we assessed the haemodynamic response to exercise in HFpEF patients.
Methods and results
Eleven HFpEF patients (73 ± 7 years, 7 females/4 males) and 13 healthy controls (70 ± 4 years, 6 females/7 males) were studied during submaximal and maximal exercise. The cardiac output (Qc, acetylene rebreathing) response to exercise was determined from linear regression of Qc and VO2 (Douglas bags) at rest, ∼30% and ∼60% of peak VO2, and maximal exercise. Peak VO2 was lower in HFpEF patients than in controls (13.7 ± 3.4 vs. 21.6 ± 3.6 mL/kg/min; P < 0.001), while indices of cardiac reserve were not statistically different: peak cardiac power output [CPO = Qc × mean arterial pressure (MAP); HFpEF 1790 ± 509 vs. controls 2119 ± 581 L/mmHg/min; P = 0.20]; peak stroke work [SW = stroke volume (SV) × MAP; HFpEF 13 429 ± 2269 vs. controls 13 200 ± 3610 mL/mmHg; P = 0.80]. The ΔQc/ΔVO2 slope was abnormally elevated in HFpEF patients vs. controls (11.2 ±3.6 vs. 8.3 ± 1.5; P = 0.015).
Contrary to our hypothesis, cardiac reserve is not significantly impaired in well-compensated outpatients with HFpEF. The abnormal haemodynamic response to exercise (decreased peak VO2, increased ΔQc/ΔVO2 slope) is similar to that observed in patients with mitochondrial myopathies, suggesting an element of impaired skeletal muscle oxidative metabolism. This impairment may limit functional capacity by two mechanisms: (i) premature skeletal muscle fatigue and (ii) metabolic signals to increase the cardiac output response to exercise which may be poorly tolerated by a left ventricle with impaired diastolic function.
PMCID: PMC3220394  PMID: 21979991
Cardiac output response to exercise; Haemodynamic response to exercise; Heart failure with preserved ejection fraction; Exercise capacity; Myocardial contractile reserve; Oxygen consumption
8.  Gender Differences in Adolescent Premarital Sexual Permissiveness in Three Asian Cities: Effects of Gender-Role Attitudes 
Gender is an important factor in understanding premarital sexual attitudes and behaviors. Many studies indicate that males are more likely to initiate sexual intercourse and have more permissive perceptions about sex than females. Yet few studies have explored possible reasons for these gender differences. With samples of unmarried adolescents in three Asian cities influenced by Confucian cultures, this paper investigates the relationship between underlying gender norms and these differences in adolescents’ premarital sexual permissiveness.
16,554 unmarried participants aged 15–24 were recruited in the Three-City Asian Study of Adolescents and Youth, a collaborative survey conducted in 2006–2007 in urban and rural areas of Hanoi, Shanghai and Taipei, with 6204, 6023 and 4327 from each city respectively. All of the adolescents were administered face-to-face interviews, coupled with Computer Assisted Self Interview (CASI) for sensitive questions. Scales on gender-role attitudes and on premarital sexual permissiveness for both male and female respondents were developed and applied to our analysis of the data. Multi-linear regression was used to analyze the relationship between gender-role attitudes and sexual permissiveness.
Male respondents in each city held more permissive attitudes towards premarital sex than did females with both boys and girls expressing greater permissiveness to male premarital sexual behaviors. Boys also expressed more traditional attitudes to gender roles (condoning greater inequality) than did girls in each city. Adolescents’ gender-role attitudes and permissiveness to premarital sex varied considerably across the three cities, with the Vietnamese the most traditional, the Taiwanese the least traditional, and the adolescents in Shanghai in the middle. A negative association between traditional gender roles and premarital sexual permissiveness was only found among girls in Shanghai and Taipei. In Shanghai, female respondents who held more traditional gender role attitudes were more likely to exercise a double standard with respect to male as opposed to female premarital sex (OR=1.18). This relationship also applied to attitudes of both girls and boys in Taipei (OR=1.20 and OR=1.22, respectively).
Although with variation across sites, gender differences in premarital sexual permissiveness and attitudes to gender roles among adolescents were very significant in each of the three Asian cities influenced by Confucian-based values. Traditional gender norms may still be deeply rooted in the three cities, especially among females, while it is important to advocate gender equity in adolescent reproductive health programs, the pathway of traditional gender norms in influencing adolescent reproductive health outcomes must be understood, as must differences and similarities across regions.
PMCID: PMC4235609  PMID: 22340852
Gender role; Premarital sex; Attitudes; Asian; Confucian
9.  Comparison of rehydration regimens for rehabilitation of firefighters performing heavy exercise in thermal protective clothing: A report from the Fireground Rehab Evaluation (FIRE) trial 
Fire suppression activities results in cardiovascular stress, hyperthermia, and hypohydration. Fireground rehabilitation (rehab) is recommended to blunt the deleterious effects of these conditions.
We tested the hypothesis that three rehydration fluids provided after exercise in thermal protective clothing (TPC) would produce different heart rate or core temperature responses during a second bout of exercise in TPC.
On three occasions, 18 euhydrated firefighters (16 males, 2 females) wearing TPC completed a standardized, 50-minute bout of upper and lower body exercise in a hot room that mimicked the National Fire Protection Association (NFPA) rehabilitation guidelines of “two cylinders before rehab” (20 min work, 10 min recovery, 20 min work). After an initial bout of exercise, subjects were randomly assigned water, sport drink, or an intravenous (IV) infusion of normal saline equal to the amount of body mass lost during exercise. After rehydration, the subject performed a second bout of exercise. Heart rate, core and skin temperature, and exercise duration were compared with a two-way ANOVA.
Subjects were firefighters aged 28.2±11.3 years with a VO2peak of 37.4±3.4 ml/kg/min. 527±302 mL of fluid were provided during the rehabilitation period. No subject could complete either the pre- or post-rehydration 50-minute bout of exercise. Mean (SD) time to exhaustion (min) was longer (p<0.001) in bout 1 (25.9±12.9 min. water, 28.0±14.1 min. sport drink, 27.4±13.8 min. IV) compared to bout 2 (15.6±9.6 min. water, 14.7±8.6 min. sport drink, 15.7±8.0 min. IV) for all groups but did not differ by intervention. All subjects approached age predicted maximum heart rate at the end of bout 1 (180±11 bpm) and bout 2 (176±13 bpm). Core temperature rose 1.1±0.7°C during bout 1 and 0.5±0.4°C during bout 2. Core temperature, heart rate, and exercise time during bout 2 did not differ between rehydration fluids.
Performance during a second bout of exercise in TPC did not differ when firefighters were rehydrated with water, sport drink, or IV normal saline when full rehydration is provided. Of concern was the inability of all subjects to complete two consecutive periods of heavy exercise in TPC suggesting the NFPA “two cylinders before rehab” guideline may not be appropriate in continuous heavy work scenarios.
PMCID: PMC2867093  PMID: 20095824
Cardiovascular strain; Thermal Stress; Performance; Hydration
10.  Association between heart rate at rest and myocardial perfusion in patients with acute myocardial infarction undergoing cardiac rehabilitation – a pilot study 
This study was conducted to determine if there was a link among heart rate at rest (rHR), muscle volume changes, and single photon emission computed tomography (SPECT) parameters after 6-month cardiac rehabilitation in patients with acute myocardial infarction (AMI).
Material and methods
Twenty-nine consecutive AMI patients (mean age: 63.0 ±9.1 years) who received appropriate percutaneous coronary intervention on admission were enrolled. 99mTc-Sestamibi myocardial SPECT images were obtained at the early (30 min) and delayed (4 h) phases after tracer injection at 2 weeks (0M) and 6 months (6M) after the onset of AMI. Within a few days of SPECT, all patients underwent cardiopulmonary exercise test for evaluation of cardiac rehabilitation effects. Before the initiation of exercise test, leg muscle volume was measured. All patients were stratified into the ≥ 70 beats per minute (bpm) (n = 15) or < 70 bpm (n = 14) group based on rHR at 6M.
There were no significant differences in the recanalization time, peak cardiac enzyme, or initial left ventricular ejection fraction between the two groups. After the 6-month training, the muscle volume changes in the lower limbs (< 70 bpm, 0.23 ±0.22; ≥ 70 bpm, –0.07 ±0.26, p < 0.05) were significantly greater in the < 70 bpm group than the ≥ 70 bpm group. The decreased rate of rHR had a significant correlation with the improved global severity (r = 0.62, p = 0.001) and extent (r = 0.48, p = 0.017) of left ventricle evaluated by 99mTc-Sestamibi myocardial SPECT delayed phase.
The result of this preliminary study demonstrated that improved myocardial perfusion was closely related to decreased rHR after cardiac rehabilitation.
PMCID: PMC3460498  PMID: 23056072
cardiac rehabilitation; exercise capacity; myocardial infarction; skeletal muscle; single photon emission computed tomography
11.  Inspiratory Muscle Fatigue Following Moderate-Intensity Exercise in the Heat 
Heavy exercise has been shown to elicit reductions in inspiratory muscle strength in healthy subjects. Our purpose was to determine the combined effects of moderate-intensity endurance exercise and a thermal load on inspiratory muscle strength in active subjects. Eight active, non heat-acclimatized female subjects (23.5 ± 1.4 yr; VO2max = 39.8 ± 2.4 randomly performed two 40 min endurance exercise bouts (60% VO2max) in either a thermo-neutral (22°C/21% RH) or hot (37°C/33% RH) environment on separate days. Maximal sustained inspiratory mouth pressure (PImax) was obtained pre and post exercise as an index of inspiratory muscle strength. Additional variables obtained every 10 min during the endurance exercise bouts included: rectal temperature (TRE), heart rate (HR), minute ventilation (VE), oxygen uptake (VO2), tidal volume (VT), breathing frequency (Fb), and ratings of perceived exertion and dyspnea (RPE/RPD). Data were analyzed with repeated measures ANOVA. PImax was significantly reduced (p < 0.05) after exercise in the hot environment when compared to baseline and when compared to post exercise values in the thermo-neutral environment. PImax was unchanged from baseline following exercise in the thermo-neutral environment. HR and TRE were significantly higher (p < 0.05) in the hot compared to the thermo-neutral environment. VE and VO2 were not significantly different between conditions. VT was unchanged between conditions whereas Fb was higher (p < 0.05) in the hot condition compared to thermo-neutral. RPE was not significantly different between conditions. RPD was significantly higher (p < 0.05) in the hot compared to the thermo-neutral environment. We conclude that moderate-intensity endurance exercise (60% VO2max) in a hot environment elicits significant reductions in inspiratory muscle strength in unfit females. This finding is novel in that previous studies conducted in a thermo-neutral environment have shown that an exercise intensity of >80% VO2max is required to elicit reductions in inspiratory muscle strength. In addition, dyspnea perception during exercise is greater in a hot environment, compared to thermo-neutral, at a similar level of VE and VO2.
Key PointsThe combined effects of a heat load and exercise on inspiratory muscle strength were investigated in untrained female subjects.Previous studies have shown that a very high exercise intensity (> 80% VO2max) is required to elicit reductions in inspiratory muscle strength.Prolonged submaximal exercise (40-min/60% VO2max) in a hot environment significantly reduced inspiratory muscle strength in untrained females whereas the same intensity in a thermo-neutral environment had no effect on inspiratory muscle function.These reductions in inspiratory muscle strength may be related to competition for blood flow among the locomotor, inspiratory, and cutaneous circulations.
PMCID: PMC3887326  PMID: 24453527
Control of breathing; endurance; respiratory function; thermal load
12.  Continuous low- to moderate-intensity exercise training is as effective as moderate- to high-intensity exercise training at lowering blood HbA1c in obese type 2 diabetes patients 
Diabetologia  2009;52(9):1789-1797.
Exercise represents an effective interventional strategy to improve glycaemic control in type 2 diabetes patients. However, the impact of exercise intensity on the benefits of exercise training remains to be established. In the present study, we compared the clinical benefits of 6 months of continuous low- to moderate-intensity exercise training with those of continuous moderate- to high-intensity exercise training, matched for energy expenditure, in obese type 2 diabetes patients.
Fifty male obese type 2 diabetes patients (age 59 ± 8 years, BMI 32 ± 4 kg/m2) participated in a 6 month continuous endurance-type exercise training programme. All participants performed three supervised exercise sessions per week, either 55 min at 50% of whole body peak oxygen uptake \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ \left( {\mathop V\limits^{ \cdot } {\text{O}}_{{2{\text{peak}}}} } \right) $$\end{document} (low to moderate intensity) or 40 min at 75% of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ \mathop V\limits^{ \cdot } {\text{O}}_{{2{\text{peak}}}} $$\end{document} (moderate to high intensity). Oral glucose tolerance, blood glycated haemoglobin, lipid profile, body composition, maximal workload capacity, whole body and skeletal muscle oxidative capacity and skeletal muscle fibre type composition were assessed before and after 2 and 6 months of intervention.
The entire 6 month intervention programme was completed by 37 participants. Continuous endurance-type exercise training reduced blood glycated haemoglobin levels, LDL-cholesterol concentrations, body weight and leg fat mass, and increased \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ \mathop V\limits^{ \cdot } {\text{O}}_{{2{\text{peak}}}} $$\end{document}, lean muscle mass and skeletal muscle cytochrome c oxidase and citrate synthase activity (p < 0.05). No differences were observed between the groups training at low to moderate or moderate to high intensity.
When matched for energy cost, prolonged continuous low- to moderate-intensity endurance-type exercise training is equally effective as continuous moderate- to high-intensity training in lowering blood glycated haemoglobin and increasing whole body and skeletal muscle oxidative capacity in obese type 2 diabetes patients.
Trial registration:
PMCID: PMC2723667  PMID: 19370339
Diabetes; Glycaemic control; Lifestyle intervention; Training modalities
13.  Effect of Intermittent Sub-Maximal Exercise on Percent Body Fat Using Leg-To-Leg Bioelectrical Impedance Analysis in Children 
The purpose of this investigation was to determine the effect of intermittent sub-maximal exercise on percent body fat (%BF) estimated by leg-to-leg bioelectrical impedance analysis (LBIA) in children. Fifty-nine children (29 girls; 30 boys) mean age 9.0 ± 1.3 years participated in this study. LBIA measured %BF values were obtained immediately before and within five minutes after completing an intermittent exercise protocol consisting of three 8-minute sub-maximal exercise bouts (2.74 km·hr-1, 0% grade; 4.03 km·hr-1, 0% grade; and 5.47 km·hr-1, 0% grade) each separated by a 5-min seated rest period. The three exercise bouts corresponded to 56%, 61% and 71% of maximal heart rate. Significant differences (p < 0.001) were observed for fat mass, fat free mass, total body water, and body weight, post-exercise in both groups. Significant reductions (p < 0.001) in %BF were observed post-exercise in the female (23.1 ± 9.9 vs. 21.8 ± 9. 9 %) and male (23.3 ± 10.5 vs. 21.8 ± 10.2 %) children when compared to pre-exercise values. However, for the majority of the subjects (females = 86%; males = 73%) the decrease in %BF post- exercise was less than 2.0 %BF. These data indicate that sub-maximal intermittent exercise, that may be representative of daily free-form activities in children, will most likely have a limited impact on %BF estimates when the assessment is performed immediately post-exercise.
Key PointsLBIA measures of body weight, percent body fat, fat mass, fat free mass and total body water were significantly lower after the intermittent sub-maximal exercise.The reductions in percent body fat for girls (1.4%) and boys (1.5%) compare favorably to previous investigations.Intermittent exercise, that may be representative of daily free-form activities in children, will most likely have a limited impact on LBIA percent body fat estimates
PMCID: PMC3842143  PMID: 24353460
Bioelectrical impedance analysis; body fat; sub-maximal exercise; children
14.  Lactate and Glucose Exchange across the Forearm, Legs, and Splanchnic Bed during and after Prolonged Leg Exercise 
The net exchange of glucose and lactate across the leg and the splanchnic bed and the arterialdeep venous (A-DV) differences for these substrates in the forearm were determined in healthy subjects during 3-3.5 h of leg exercise (bicycle ergometer) at 58% maximum O2 uptake and during a 40-min post-exercise recovery period.
Leg glucose uptake rose 16-fold during exercise and throughout the exercise period exceeded splanchnic glucose output. The latter reached a peak increment (3.5 times basal) at 90 min and fell by 60% during the third hour. As a result, blood glucose declined 40%, reaching frank hypoglycemia (blood glucose, <45 mg/dl) in 50% of subjects at 3.5 h.
Splanchnic lactate uptake rose progressively during exercise to values four times the basal rate at 3 h in association with a rise in arterial lactate to 1.5 mM. There was, however, no significant net output of lactate from the legs beyond 90 min of exercise. In contrast, the A-DV lactate difference in the forearm became progressively more negative throughout exercise, reaching values three times the basal level at 3.5 h. The rise in arterial lactate during exercise was proportional to the elevation in plasma epinephrine, which rose ninefold.
During recovery, splanchnic lactate uptake rose further to values six times the basal rate, whereas lactate output by the legs was no greater than in the basal state. The A-DV lactate difference in the forearm became even more negative than during exercise, reaching values four times basal. During exercise as well as recovery, forearm uptake of blood glucose could account for no more than 25-67% of forearm lactate release. Leg glucose uptake during recovery was threefold to fivefold higher than in the basal state in the face of plasma insulin concentrations that were 60% below basal and in association with a respiratory exchange ratio of 0.7.
We conclude that (a) during prolonged leg exercise at 58% maximum O2 uptake an imbalance between splanchnic glucose production and leg glucose utilization results in a fall in blood glucose that may reach hypoglycemic levels in healthy subjects; (b) there is a marked increase in the uptake of lactate by the splanchnic bed that cannot be attributed to increased output of lactate from the exercising legs; (c) lactate is released by forearm muscle and, together with other relatively inactive muscle, may be an important source of the increased lactate turnover during and after prolonged leg exercise; (d) the increasingly negative A-DV lactate difference in the forearm cannot be accounted for by uptake of blood glucose, suggesting the breakdown of glycogen in forearm muscle during and after leg exercise; (e) increased glucose uptake by the legs in association with hypoinsulinemia during recovery suggests an increase in insulin sensitivity that permits glycogen repletion in previously exercising muscle in the absence of food ingestion; and (f) the evidence for increased lactate output in the forearm and augmented glucose uptake in the legs during recovery raises the possibility that after leg exercise glycogen stores are decreasing in muscle that was relatively inactive (e.g., that of the forearm) while increasing in the previously exercising leg muscles.
PMCID: PMC371167  PMID: 7054242
15.  Ischemic preconditioning accelerates muscle deoxygenation dynamics and enhances exercise endurance during the work-to-work test 
Physiological Reports  2015;3(5):e12395.
Ischemic preconditioning (IPC) improves maximal exercise performance. However, the potential mechanism(s) underlying the beneficial effects of IPC remain unknown. The dynamics of pulmonary oxygen uptake (VO2) and muscle deoxygenation during exercise is frequently used for assessing O2 supply and extraction. Thus, this study examined the effects of IPC on systemic and local O2 dynamics during the incremental step transitions from low- to moderate- and from moderate- to severe-intensity exercise. Fifteen healthy, male subjects were instructed to perform the work-to-work cycling exercise test, which was preceded by the control (no occlusion) or IPC (3 × 5 min, bilateral leg occlusion at >300 mmHg) treatments. The work-to-work test was performed by gradually increasing the exercise intensity as follows: low intensity at 30 W for 3 min, moderate intensity at 90% of the gas exchange threshold (GET) for 4 min, and severe intensity at 70% of the difference between the GET and VO2 peak until exhaustion. During the exercise test, the breath-by-breath pulmonary VO2 and near-infrared spectroscopy-derived muscle deoxygenation were continuously recorded. Exercise endurance during severe-intensity exercise was significantly enhanced by IPC. There were no significant differences in pulmonary VO2 dynamics between treatments. In contrast, muscle deoxygenation dynamics in the step transition from low- to moderate-intensity was significantly faster in IPC than in CON (27.2 ± 2.9 vs. 19.8 ± 0.9 sec, P < 0.05). The present findings showed that IPC accelerated muscle deoxygenation dynamics in moderate-intensity exercise and enhanced severe-intensity exercise endurance during work-to-work test. The IPC-induced effects may result from mitochondrial activation in skeletal muscle, as indicated by the accelerated O2 extraction.
PMCID: PMC4463825  PMID: 25952936
Exercise; mitochondria; near-infrared spectroscopy; nitric oxide; skeletal muscle
16.  Male Circumcision at Different Ages in Rwanda: A Cost-Effectiveness Study 
PLoS Medicine  2010;7(1):e1000211.
Agnes Binagwaho and colleagues predict that circumcision of newborn boys would be effective and cost-saving as a long-term strategy to prevent HIV in Rwanda.
There is strong evidence showing that male circumcision (MC) reduces HIV infection and other sexually transmitted infections (STIs). In Rwanda, where adult HIV prevalence is 3%, MC is not a traditional practice. The Rwanda National AIDS Commission modelled cost and effects of MC at different ages to inform policy and programmatic decisions in relation to introducing MC. This study was necessary because the MC debate in Southern Africa has focused primarily on MC for adults. Further, this is the first time, to our knowledge, that a cost-effectiveness study on MC has been carried out in a country where HIV prevalence is below 5%.
Methods and Findings
A cost-effectiveness model was developed and applied to three hypothetical cohorts in Rwanda: newborns, adolescents, and adult men. Effectiveness was defined as the number of HIV infections averted, and was calculated as the product of the number of people susceptible to HIV infection in the cohort, the HIV incidence rate at different ages, and the protective effect of MC; discounted back to the year of circumcision and summed over the life expectancy of the circumcised person. Direct costs were based on interviews with experienced health care providers to determine inputs involved in the procedure (from consumables to staff time) and related prices. Other costs included training, patient counselling, treatment of adverse events, and promotion campaigns, and they were adjusted for the averted lifetime cost of health care (antiretroviral therapy [ART], opportunistic infection [OI], laboratory tests). One-way sensitivity analysis was performed by varying the main inputs of the model, and thresholds were calculated at which each intervention is no longer cost-saving and at which an intervention costs more than one gross domestic product (GDP) per capita per life-year gained. Results: Neonatal MC is less expensive than adolescent and adult MC (US$15 instead of US$59 per procedure) and is cost-saving (the cost-effectiveness ratio is negative), even though savings from infant circumcision will be realized later in time. The cost per infection averted is US$3,932 for adolescent MC and US$4,949 for adult MC. Results for infant MC appear robust. Infant MC remains highly cost-effective across a reasonable range of variation in the base case scenario. Adolescent MC is highly cost-effective for the base case scenario but this high cost-effectiveness is not robust to small changes in the input variables. Adult MC is neither cost-saving nor highly cost-effective when considering only the direct benefit for the circumcised man.
The study suggests that Rwanda should be simultaneously scaling up circumcision across a broad range of age groups, with high priority to the very young. Infant MC can be integrated into existing health services (i.e., neonatal visits and vaccination sessions) and over time has better potential than adolescent and adult circumcision to achieve the very high coverage of the population required for maximal reduction of HIV incidence. In the presence of infant MC, adolescent and adult MC would evolve into a “catch-up” campaign that would be needed at the start of the program but would eventually become superfluous.
Please see later in the article for the Editors' Summary
Editors' Summary
Acquired immunodeficiency syndrome (AIDS) has killed more than 25 million people since 1981 and more than 31 million people (22 million in sub-Saharan Africa alone) are now infected with the human immunodeficiency virus (HIV), which causes AIDS. There is no cure for HIV/AIDS and no vaccine against HIV infection. Consequently, prevention of HIV transmission is extremely important. HIV is most often spread through unprotected sex with an infected partner. Individuals can reduce their risk of HIV infection, therefore, by abstaining from sex, by having one or a few sexual partners, and by always using a male or female condom. In addition, male circumcision—the removal of the foreskin, the loose fold of skin that covers the head of penis—can halve HIV transmission rates to men resulting from sex with women. Thus, as part of its HIV prevention strategy, the World Health Organization (WHO) recommends that male circumcision programs be scaled up in countries where there is a generalized HIV epidemic and where few men are circumcised.
Why Was This Study Done?
One such country is Rwanda. Here, 3% of the adult population is infected with HIV but only 15% of men are circumcised—worldwide, about 30% of men are circumcised. Demand for circumcision is increasing in Rwanda but, before policy makers introduce a country-wide male circumcision program, they need to identify the most cost-effective way to increase circumcision rates. In particular, they need to decide the age at which circumcision should be offered. Circumcision soon after birth (neonatal circumcision) is quick and simple and rarely causes any complications. Circumcision of adolescents and adults is more complex and has a higher complication rate. Although several studies have investigated the cost-effectiveness (the balance between the clinical and financial costs of a medical intervention and its benefits) of circumcision in adult men, little is known about its cost-effectiveness in newborn boys. In this study, which is one of several studies on male circumcision being organized by the National AIDS Control Commission in Rwanda, the researchers model the cost-effectiveness of circumcision at different ages.
What Did the Researchers Do and Find?
The researchers developed a simple cost-effectiveness model and applied it to three hypothetical groups of Rwandans: newborn boys, adolescent boys, and adult men. For their model, the researchers calculated the effectiveness of male circumcision (the number of HIV infections averted) by estimating the reduction in the annual number of new HIV infections over time. They obtained estimates of the costs of circumcision (including the costs of consumables, staff time, and treatment of complications) from health care providers and adjusted these costs for the money saved through not needing to treat HIV in males in whom circumcision prevented infection. Using their model, the researchers estimate that each neonatal male circumcision would cost US$15 whereas each adolescent or adult male circumcision would cost US$59. Neonatal male circumcision, they report, would be cost-saving. That is, over a lifetime, neonatal male circumcision would save more money than it costs. Finally, using the WHO definition of cost-effectiveness (for a cost-effective intervention, the additional cost incurred to gain one year of life must be less than a country's per capita gross domestic product), the researchers estimate that, although adolescent circumcision would be highly cost-effective, circumcision of adult men would only be potentially cost-effective (but would likely prove cost-effective if the additional infections that would occur from men to their partners without a circumcision program were also taken into account).
What Do These Findings Mean?
As with all modeling studies, the accuracy of these findings depends on the many assumptions included in the model. However, the findings suggest that male circumcision for infants for the prevention of HIV infection later in life is highly cost-effective and likely to be cost-saving and that circumcision for adolescents is cost-effective. The researchers suggest, therefore, that policy makers in Rwanda and in countries with similar HIV infection and circumcision rates should scale up male circumcision programs across all age groups, with high priority being given to the very young. If infants are routinely circumcised, they suggest, circumcision of adolescent and adult males would become a “catch-up” campaign that would be needed at the start of the program but that would become superfluous over time. Such an approach would represent a switch from managing the HIV epidemic as an emergency towards focusing on sustainable, long-term solutions to this major public-health problem.
Additional Information
Please access these Web sites via the online version of this summary at
This study is further discussed in a PLoS Medicine Perspective by Seth Kalichman
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
Information is available from the Joint United Nations Programme on HIV/AIDS (UNAIDS) on HIV infection and AIDS and on male circumcision in relation to HIV and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on HIV and AIDS in Africa, and on circumcision and HIV (some information in English and Spanish)
More information about male circumcision is available from the Clearinghouse on Male Circumcision
The National AIDS Control Commission of Rwanda provides detailed information about HIV/AIDS in Rwanda (in English and French)
PMCID: PMC2808207  PMID: 20098721
17.  The oxygen delivery response to acute hypoxia during incremental knee extension exercise differs in active and trained males 
It is well known that hypoxic exercise in healthy individuals increases limb blood flow, leg oxygen extraction and limb vascular conductance during knee extension exercise. However, the effect of hypoxia on cardiac output, and total vascular conductance is less clear. Furthermore, the oxygen delivery response to hypoxic exercise in well trained individuals is not well known. Therefore our aim was to determine the cardiac output (Doppler echocardiography), vascular conductance, limb blood flow (Doppler echocardiography) and muscle oxygenation response during hypoxic knee extension in normally active and endurance-trained males.
Ten normally active and nine endurance-trained males (VO2max = 46.1 and 65.5 mL/kg/min, respectively) performed 2 leg knee extension at 25, 50, 75 and 100% of their maximum intensity in both normoxic and hypoxic conditions (FIO2 = 15%; randomized order). Results were analyzed with a 2-way mixed model ANOVA (group × intensity).
The main finding was that in normally active individuals hypoxic sub-maximal exercise (25 – 75% of maximum intensity) brought about a 3 fold increase in limb blood flow but decreased stroke volume compared to normoxia. In the trained group there were no significant changes in stroke volume, cardiac output and limb blood flow at sub-maximal intensities (compared to normoxia). During maximal intensity hypoxic exercise limb blood flow increased approximately 300 mL/min compared to maximal intensity normoxic exercise.
Cardiorespiratory fitness likely influences the oxygen delivery response to hypoxic exercise both at a systemic and limb level. The increase in limb blood flow during maximal exercise in hypoxia (both active and trained individuals) suggests a hypoxic stimulus that is not present in normoxic conditions.
PMCID: PMC2526084  PMID: 18700024
18.  Physiological response to a breed evaluation field test in Icelandic horses 
Animal  2014;8(3):431-439.
This study examined the response in terms of heart rate (HR), respiratory rate (RR), haematocrit (Htc), rectal temperature (RT), and some plasma variables in Icelandic horses of different sexes and ages performing the riding assessment in a breed evaluation field test (BEFT). The study was conducted in Iceland on 266 horses (180 mares and 86 stallions, divided into four age groups; 4, 5, 6 and ⩾7 years old). RT and RR were recorded and blood samples were taken before the warm-up and after the riding assessment. Horse HR, velocity and distance were recorded during the warm-up, the riding assessment and a 5-min recovery period. The distance covered in the BEFT was 2.9±0.4 km (range: 1.8 to 3.8 km, n=248), the duration was 9:37±1:22 min:s (range: 5:07 to 15:32 min:s, n=260) and the average speed was 17.8±1.4 km/h (range: 13.2 to 21.3 km/h, n=248). Average HR was 184±13 b.p.m. (range: 138 to 210 b.p.m., n=102) and peak HR 224±9 b.p.m. (range: 195 to 238 b.p.m., n=102), and 36% of the BEFT was performed at HR ⩾200 b.p.m. Post-exercise plasma lactate concentration (Lac) was 18.0±6.5 mmol/l (range: 2.1 to 34.4 mmol/l, n=266), and there was an increase in total plasma protein, plasma creatine kinase and aspartate amino transferase concentration, as well as RR, RT and Htc. Stallions covered a longer total distance (in the warm-up and BEFT) (P<0.05), at a faster speed during BEFT (P<0.001) than mares and had higher Htc and lower HR and post-exercise Lac values. There were few effects of age, but the 4- and 5-year-old horses had lower Htc than older horses and 4-year-old horses had higher post-exercise RR than older horses, although they were ridden for a shorter distance, shorter duration and at lower peak velocity (P<0.1). The results showed that the riding assessment in the BEFT is a high-intensity exercise. The results also showed that aerobic fitness was higher in stallions and that age had a limited effect on the physiological response. It is suggested that these results should be used as a guide for the development of training programmes and fitness tests in Icelandic horses that would improve both performance and welfare of the horse.
PMCID: PMC3942816  PMID: 24387835
exercise physiology; hematological parameters; lactate; heart rate; Icelandic horse
19.  Assessing Causality in the Association between Child Adiposity and Physical Activity Levels: A Mendelian Randomization Analysis 
PLoS Medicine  2014;11(3):e1001618.
Here, Timpson and colleagues performed a Mendelian Randomization analysis to determine whether childhood adiposity causally influences levels of physical activity. The results suggest that increased adiposity causes a reduction in physical activity in children; however, this study does not exclude lower physical activity also leading to increasing adiposity.
Please see later in the article for the Editors' Summary
Cross-sectional studies have shown that objectively measured physical activity is associated with childhood adiposity, and a strong inverse dose–response association with body mass index (BMI) has been found. However, few studies have explored the extent to which this association reflects reverse causation. We aimed to determine whether childhood adiposity causally influences levels of physical activity using genetic variants reliably associated with adiposity to estimate causal effects.
Methods and Findings
The Avon Longitudinal Study of Parents and Children collected data on objectively assessed activity levels of 4,296 children at age 11 y with recorded BMI and genotypic data. We used 32 established genetic correlates of BMI combined in a weighted allelic score as an instrumental variable for adiposity to estimate the causal effect of adiposity on activity.
In observational analysis, a 3.3 kg/m2 (one standard deviation) higher BMI was associated with 22.3 (95% CI, 17.0, 27.6) movement counts/min less total physical activity (p = 1.6×10−16), 2.6 (2.1, 3.1) min/d less moderate-to-vigorous-intensity activity (p = 3.7×10−29), and 3.5 (1.5, 5.5) min/d more sedentary time (p = 5.0×10−4). In Mendelian randomization analyses, the same difference in BMI was associated with 32.4 (0.9, 63.9) movement counts/min less total physical activity (p = 0.04) (∼5.3% of the mean counts/minute), 2.8 (0.1, 5.5) min/d less moderate-to-vigorous-intensity activity (p = 0.04), and 13.2 (1.3, 25.2) min/d more sedentary time (p = 0.03). There was no strong evidence for a difference between variable estimates from observational estimates. Similar results were obtained using fat mass index. Low power and poor instrumentation of activity limited causal analysis of the influence of physical activity on BMI.
Our results suggest that increased adiposity causes a reduction in physical activity in children and support research into the targeting of BMI in efforts to increase childhood activity levels. Importantly, this does not exclude lower physical activity also leading to increased adiposity, i.e., bidirectional causation.
Please see later in the article for the Editors' Summary
Editors' Summary
The World Health Organization estimates that globally at least 42 million children under the age of five are obese. The World Health Organization recommends that all children undertake at least one hour of physical activity daily, on the basis that increased physical activity will reduce or prevent excessive weight gain in children and adolescents. In practice, while numerous studies have shown that body mass index (BMI) shows a strong inverse correlation with physical activity (i.e., active children are thinner than sedentary ones), exercise programs specifically targeted at obese children have had only very limited success in reducing weight. The reasons for this are not clear, although environmental factors such as watching television and lack of exercise facilities are traditionally blamed.
Why Was This Study Done?
One of the reasons why obese children do not lose weight through exercise might be that being fat in itself leads to a decrease in physical activity. This is termed reverse causation, i.e., obesity causes sedentary behavior, rather than the other way around. The potential influence of environmental factors (e.g., lack of opportunity to exercise) makes it difficult to prove this argument. Recent research has demonstrated that specific genotypes are related to obesity in children. Specific variations within the DNA of individual genes (single nucleotide polymorphisms, or SNPs) are more common in obese individuals and predispose to greater adiposity across the weight distribution. While adiposity itself can be influenced by many environmental factors that complicate the interpretation of observed associations, at the population level, genetic variation is not related to the same factors, and over the life course cannot be changed. Investigations that exploit these properties of genetic associations to inform the interpretation of observed associations are termed Mendelian randomization studies. This research technique is used to reduce the influence of confounding environmental factors on an observed clinical condition. The authors of this study use Mendelian randomization to determine whether a genetic tendency towards high BMI and fat mass is correlated with reduced levels of physical activity in a large cohort of children.
What Did the Researchers Do and Find?
The researchers looked at a cohort of children from a large long-term health research project (the Avon Longitudinal Study of Parents and Children). BMI and total body fat were recorded. Total daily activity was measured via a small movement-counting device. In addition, the participants underwent genotyping to detect the presence of several SNPs known to be linked to obesity. For each child a total BMI allelic score was determined based on the number of obesity-related genetic variants carried by that individual. The association between obesity and reduced physical activity was then studied in two ways. Direct correlation between actual BMI and physical activity was measured (observational data). Separately, the link between BMI allelic score and physical activity was also determined (Mendelian randomization or instrumental variable analysis). The observational data showed that boys were more active than girls and had lower BMI. Across both sexes, a higher-than-average BMI was associated with lower daily activity. In genetic analyses, allelic score had a positive correlation with BMI, with one particular SNP being most strongly linked to high BMI and total fat mass. A high allelic score for BMI was also correlated with lower levels of daily physical activity. The authors conclude that children who are obese and have an inherent predisposition to high BMI also have a propensity to reduced levels of physical activity, which may compound their weight gain.
What Do These Findings Mean?
This study provides evidence that being fat is in itself a risk factor for low activity levels, separately from external environmental influences. This may be an example of “reverse causation,” i.e., high BMI causes a reduction in physical activity. Alternatively, there may be a bidirectional causality, so that those with a genetic predisposition to high fat mass exercise less, leading to higher BMI, and so on, in a vicious circle. A significant limitation of the study is that validated allelic scores for physical activity are not available. Thus, it is not possible to determine whether individuals with a high allelic score for BMI also have a propensity to exercise less, or whether it is simply the circumstance of being overweight that discourages activity. This study does suggest that trying to persuade obese children to lose weight by exercising more is likely to be ineffective unless additional strategies to reduce BMI, such as strict diet control, are also implemented.
Additional Information
Please access these websites via the online version of this summary at
The US Centers for Disease Control and Prevention provides obesity-related statistics, details of prevention programs, and an overview on public health strategy in the United States
A more worldwide view is given by the World Health Organization
The UK National Health Service website gives information on physical activity guidelines for different age groups
The International Obesity Task Force is a network of organizations that seeks to alert the world to the growing health crisis threatened by soaring levels of obesity
MedlinePlus—which brings together authoritative information from the US National Library of Medicine, National Institutes of Health, and other government agencies and health-related organizations—has a page on obesity
Additional information on the Avon Longitudinal Study of Parents and Children is available
The British Medical Journal has an article that describes Mendelian randomization
PMCID: PMC3958348  PMID: 24642734
20.  Low-dose propranolol and exercise capacity in postural tachycardia syndrome 
Neurology  2013;80(21):1927-1933.
To determine the effect of low-dose propranolol on maximal exercise capacity in patients with postural tachycardia syndrome (POTS).
We compared the effect of placebo vs a single low dose of propranolol (20 mg) on peak oxygen consumption (VO2max), an established measure of exercise capacity, in 11 patients with POTS and 7 healthy subjects in a randomized, double-blind study. Subjects exercised on a semirecumbent bicycle, with increasing intervals of resistance to maximal effort.
Maximal exercise capacity was similar between groups following placebo. Low-dose propranolol improved VO2max in patients with POTS (24.5 ± 0.7 placebo vs 27.6 ± 1.0 mL/min/kg propranolol; p = 0.024), but not healthy subjects. The increase in VO2max in POTS was associated with attenuated peak heart rate responses (142 ± 8 propranolol vs 165 ± 4 bpm placebo; p = 0.005) and improved stroke volume (81 ± 4 propranolol vs 67 ± 3 mL placebo; p = 0.013). In a separate cohort of POTS patients, neither high-dose propranolol (80 mg) nor metoprolol (100 mg) improved VO2max, despite similar lowering of heart rate.
These findings suggest that nonselective β-blockade with propranolol, when used at the low doses frequently used for treatment of POTS, may provide a modest beneficial effect to improve heart rate control and exercise capacity.
Classification of evidence:
This study provides Class II evidence that a single low dose of propranolol (20 mg) as compared with placebo is useful in increasing maximum exercise capacity measured 1 hour after medication.
PMCID: PMC3716342  PMID: 23616163
21.  Gender differences in myocardial function and arterio-ventricular coupling in response to maximal exercise in adolescent floor-ball players 
The hemodynamic and cardiac responses to exercise have been widely investigated in adults. However, little is known regarding myocardial performance in response to a short bout of maximal exercise in adolescents. We therefore sought to study alterations in myocardial function and investigate sex-influences in young athletes after maximal cardiopulmonary testing.
51 adolescent (13-19 years old) floor-ball players (24 females) were recruited. All subjects underwent a maximal exercise test to determine maximal oxygen uptake (VO2max) and cardiac output. Cardiac performance was investigated using conventional and tissue velocity imaging, as well as 2D strain echocardiography before and 30 minutes following exercise. Arterio-ventricular coupling was evaluated by means of single beat ventricular elastance and arterial elastance.
Compared to baseline the early diastolic myocardial velocity (E′LV) at the basal left ventricular (LV) segments declined significantly (females: E′LV: 14.7 +/- 2.6 to 13.6 +/- 2.9 cm/s; males: 15.2 +/- 2.2 to 13.9 +/- 2.3 cm/s, p < 0.001 for both). Similarly, 2D strain decreased significantly following exercise (2D strain LV: from 21.5 +/- 2.4 to 20.2 +/- 2.7% in females, and from 20 +/- 1 to 17.9 +/- 1.5% in males, p < 0.05 for both). However, there were no significant changes in LV contractility estimated by elastance in either sex following exercise (p > 0.05). Arterial elastance) Ea) at baseline was identified as the only predictor of VO2max in males (r = 0.76, p < 0.001) but not in females (p > 0.05).
The present study demonstrates that vigorous exercise of short duration results in a significant decrease of longitudinal myocardial motion in both sexes. However, in view of unaltered end systolic LV elastance (Ees), these reductions most probably reflect changes in the loading conditions and not an attenuation of myocardial function per se. Importantly, we show that arterial load at rest acts as a strong predictor of VO2max in males but not in female subjects.
PMCID: PMC4084409  PMID: 25045524
Exercise; Echocardiography; Elastance; Tissue Doppler Imaging; Adolescent; Sex; Exercise stress test; Contractility; Peak VO2
22.  Gender impacts the post-exercise substrate and endocrine response in trained runners 
Although several studies have investigated gender differences in the substrate and endocrine responses during and following endurance exercise, few have studied sex differences during a more prolonged recovery period post endurance exercise. The purpose of this study was to compare and characterize the endocrine and substrate profiles of trained male and female adult runners during the three-and-a-half hour recovery period from an endurance run.
After consuming a euenergetic diet (1.8 g·kg-1·d-1 protein, 26% fat, 58% carbohydrates, 42.8 ± 1.2 kcal/kg body weight) for 8 days, blood was collected from trained male (n = 6, 21 yrs, 70 kg, 180 cm, 9% body fat, VO2peak 78.0 ± 3.4 mL·kg FFM-1·min-1) and female (n = 6, 23 y, 66 kg, 170 cm, 29% body fat, VO2peak 71.6 ± 4.5 mL·kg FFM-1·min-1) endurance runners at rest and during recovery from a 75 min run at 70% VO2peak. Circulating levels of glucose, lactate, free fatty acids (FFAs), insulin, cortisol, growth hormone (GH), and free insulin-like growth factor I (IGF-I) were measured.
During the recovery period, females experienced increases in glucose, lactate and insulin while no changes were noted in men (P < 0.05). Males experienced increases in GH and decreases in IGF-I levels respectively (P < 0.05) while no changes were observed in females. FFA levels increased during recovery from endurance exercise, but changes were not different between genders.
These data further document gender differences in substrate and endocrine changes during a prolonged recovery period following endurance exercise. Future studies are needed to evaluate the effect of differing diets and nutritional supplements on these gender-specific post-exercise substrate and endocrine differences.
PMCID: PMC2288589  PMID: 18302755
23.  Relative contribution of resting haemodynamic profile and lung function to exercise tolerance in male patients with chronic heart failure 
Heart  2001;85(2):179-184.
OBJECTIVE—To clarify the relative contribution of resting haemodynamic profile and pulmonary function to exercise capacity in patients with heart failure.
SETTING—Cardiology department and cardiac rehabilitation unit in a tertiary centre.
DESIGN—161 male patients (mean (SD) age 59 (9) years) with heart failure (New York Heart Association class II-IV, left ventricular ejection fraction 23 (7)%) underwent spirometry, alveolar capillary diffusing capacity (DLCO), and mouth inspiratory and expiratory pressures (MIP, MEP, respectively, in 100 patients). Right heart catheterisation and a symptom limited cardiopulmonary exercise test were performed in 137 patients within 3-4 days.
RESULTS—Mean peak exercise oxygen consumption (V̇O2) was 13 (3.9) ml/kg/min. Among resting haemodynamic variables only cardiac index showed a significant correlation with peak V̇O2. There were no differences in haemodynamic variables between patients with peak V̇O2 ⩽ or > 14 ml/kg/min. There was a moderate correlation (p < 0.05) between several pulmonary function variables and peak V̇O2. Forced vital capacity (3.5 (0.9) v 3.2 (0.8) l, p < 0.05) and DLCO (21.6 (6.9) v 17.7 (5.5) ml/mm Hg/min, p < 0.05) were higher in patients with peak V̇O2 > 14 ml/kg/min than in those with peak V̇O2 ⩽ 14 ml/kg/min. Using a stepwise regression analysis, the respiratory and haemodynamic variables which correlated significantly with peak V̇O2 were DLCO, MEP, and cardiac index, with an overall R value of 0.63.
CONCLUSIONS—The data confirm previous studies showing a poor correlation between resting indices of cardiac function and exercise capacity in heart failure. However, several pulmonary function variables were related to peak exercise V̇O2. In particular, lung diffusing capacity and respiratory muscle function seem to affect exercise tolerance during heart failure.

Keywords: heart failure; exercise; pulmonary function; alveolar-capillary diffusing capacity
PMCID: PMC1729632  PMID: 11156669
24.  Impact of a right ventricular impedance sensor on the cardiovascular responses to exercise in pacemaker dependent patients 
The evaluation of the heart rate (HR) response to exercise is important for the assessment of the rate response algorithm of sensor-controlled pacemakers. This study examined the effects of a right ventricular impedance sensor driven pacemaker on the cardiovascular responses to incremental exercise in pacemaker dependent patients.
Twelve patients (70.5 ± 9.5 years; 5 Females: 7 Males) implanted with an Inos 2+ closed loop stimulation (CLS) pacemaker were compared to 12 healthy age and sex matched controls (70.6 ± 4.8 years). All subjects performed the chronotropic assessment exercise protocol (CAEP). Variables of interest included HR, cardiac output (Q), oxygen uptake (Vo2) and blood pressure (BP). Data were analyzed at rest, throughout exercise and during recovery. Furthermore, patient chronotropic responses were compared to a reference chronotropic response slope for aerobic exercise.
There were no differences between groups for HR or Q response throughout exercise. At peak exercise, Vo2 ( was higher for the controls (p < 0.05). The patient chronotropic response slope was comparable to the CAEP reference slope from rest to both the anaerobic threshold (AT) and peak exercise. During recovery, no differences were observed between the groups for any parameters or for the HR decay slopes.
Up to the anaerobic threshold, the right ventricular impedance sensor driven pacemaker delivered a pacing rate that contributed to an overall cardiovascular response similar to that observed in healthy age matched subjects.
PMCID: PMC1431590  PMID: 16943865
cardiac pacing; exercise responses; chronotropic reserve index
25.  Maximal Oxygen Uptake cannot be Determined in the Incremental Phase of The Lactate Minimum Test on a Cycle Ergometer 
The aim of this study was to investigate the maximal oxygen uptake (VO2MAX) determined using the incremental phase of the lactate minimum test (LM) on a cycle ergometer. Fifteen trained men were submitted to a graded exercise test (GXT) to evaluate the VO2MAX and LM. The total durations of the GXT and LM were 11.2±1.8 minutes (CI95%:10.2-12.3 minutes) and 25.3±3.2 minutes (CI95%:23.5-27.0), respectively. For the variables measured at exhaustion in both the GXT and LM, the oxygen uptake (54.6 ± 8.1 ml·kg−1·min−1vs 50.0 ± 7.7 ml·kg−1·min−1), carbon dioxide production (66.1 ± 7.5 ml·kg−1·min−1 vs 50.4 ± 8.0 ml·kg−1·min−1), ventilation (153.9 ± 19.0 L·min−1 vs 129.9 ± 22.9 L·min−1), respiratory exchange ratio (1.22 ± 0.10 vs1.01 ± 0.05), maximal power output achieved (331.6 ± 45.8 W vs 242.4 ± 41.0 W), heart rate (183.1 ± 6.9 bpm vs175.9 ± 10.6 bpm) and lactate (10.5 ± 2.3 mmol·L−1 vs 6.6 ± 2.2 mmol·L−1) were statistically lower in the LM (p < 0.05). However, the values of rating of perceived exertion (17.6 ± 2.5 for GXT and 17.2 ± 2.3 for LM) did not differ (ES = 0.12 and CV = 7.8%). There was no good agreement between the values of the VO2MAX from the GXT and VO2PEAK from the LM, as evidenced in the Bland-Altman plot (4.7 ml·kg−1·min−1 and 0.34 L·min−1 of mean differences, respectively), as well as the high values of the upper and lower limits of agreement. We conclude that the VO2PEAK values obtained in the incremental phase of the LM underestimate the VO2MAX.
Key pointsThe VO2MAX is not attained during the incremental phase of the lactate minimum test;The physiological responses at exhaustion during LM are not similar to physiological responses measured during GXT;There is a weak agreement between the peak VO2 measured at exhaustion during LM and the VO2MAX measured during GXT.
PMCID: PMC4424467  PMID: 25983587
Maximal aerobic power; aerobic capacity; aerobic and anaerobic fitness

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