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This study examined the acute performance, cardiovascular and local muscular responses to perceived exertion-based high-intensity interval exercise using either double- or single-leg cycling. Fifteen healthy middle-aged adults completed, on separate occasions, ten 30-s double-leg intervals interspersed with 60 s passive recovery and twenty (ten with each leg) 30-s single-leg intervals interspersed with 60 s passive recovery. Impedance cardiography, blood pressure, muscle oxygenation and total haemoglobin content (near-infrared spectroscopy), oxygen consumption and power output were measured throughout each session. Normalised to the lean mass used during each trial, single-leg cycling resulted in lower power output (single-leg: 8.92 ± 1.74 W kg

[Image: see text] FKBP12 ligands such as FK506 have been shown to activate the BMP signaling pathway and facilitate tissue regeneration. However, the immunosuppressive activity of FK506 limits its clinical application. Using Heck reaction, we generated nonimmunosuppressive analogs of FK506 by fusing heterocycles to the calcineurin (CN) binding domain of FK506. Structure–activity relationships provided novel mechanistic insights into the FK506–CN interaction that can be exploited for rational design of future analogs.

The global population is aging at an unprecedented rate giving rise to a greater prevalence of age-related illnesses such as dementia and vascular disease. Dementia affects approximately 47 million individuals globally with projections of 130 million by the year 2050. Late-onset Alzheimer's disease is the most common form of dementia, accounting for approximately 75% of all cases and is characterized by a progressive decline in cognitive function, memory, and cerebral volume. The pathogenesis of Alzheimer's disease is poorly understood; however, aging, genetics, and an individual's diet and lifestyle over several decades appear to be key determinants. As there is no current cure for Alzheimer's disease, postponing or preventing the onset of Alzheimer's disease and dementia through therapeutic methods should, therefore, be targeted at individuals decades prior to an individual showing signs or symptoms of decline. As a preventative tool, resistance exercise improves memory, attention, spatial awareness, reaction time, planning, and information processing. Improvements in cognitive performance following resistance exercise and training may be mediated by peripheral elevations in the physiological biomarkers (i.e., neural and vascular) explored in this review. The purpose of this review is to discuss vascular and neuronal degeneration as a cause or consequence of dementia and Alzheimer's disease, and the biological markers of neurogenesis and blood vessel growth, function, and regulation. We will also explore the merits of acute and chronic resistance training as a strategy to postpone the onset of cognitive decline, dementia, and Alzheimer's disease.

Mild traumatic brain injury (mTBI) accounts for a large majority of traumatic brain injuries sustained globally each year. Older adults, who are already susceptible to age-related declines to neurocognitive health, appear to be at an increased risk of both sustaining an mTBI and experiencing slower or impaired recovery. There is also growing evidence that mTBI is a potential risk factor for accelerated cognitive decline and neurodegeneration. Lifestyle-based interventions are gaining prominence as a cost-effective means of maintaining cognition and brain health with age. Consequently, inter-individual variations in exercise, sleep, and dietary patterns could influence the trajectory of post-mTBI neurocognitive recovery, particularly in older adults. This review synthesises the current animal and human literature centred on the mechanisms through which lifestyle-related habits and behaviours could influence acute and longer-term neurocognitive functioning following mTBI. Numerous neuroprotective processes which are impacted by lifestyle factors have been established in animal models of TBI. However, the literature is characterised by a lack of translation to human samples and limited appraisal of the interaction between ageing and brain injury. Further research is needed to better establish the therapeutic utility of applying lifestyle-based modifications to improve post-mTBI neurocognitive outcomes in older adults.

The post‐exercise hepcidin response during prolonged ( > 2 weeks) hypoxic exposure is not well understood. We compared plasma hepcidin levels 3 h after exercise [6 × 1000 m at 90% of maximal aerobic running velocity (vVO2max)] performed in normoxia and normobaric hypoxia (3000 m simulate altitude) 1 week before, and during 14 days of normobaric hypoxia [196.2 ± 25.6 h (median: 200.8 h; range: 154.3–234.8 h) at 3000 m simulated altitude] in 10 well‐trained distance runners (six males, four females). Venous blood was also analyzed for hepcidin after 2 days of normobaric hypoxia. Hemoglobin mass (Hbmass) was measured via CO rebreathing 1 week before and after 14 days of hypoxia. Hepcidin was suppressed after 2 (Cohen's d = −2.3, 95% confidence interval: [−2.9, −1.6]) and 14 days of normobaric hypoxia (d = −1.6 [−2.6, −0.6]). Hepcidin increased from baseline, 3 h post‐exercise in normoxia (d = 0.8 [0.2, 1.3]) and hypoxia (d = 0.6 [0.3, 1.0]), both before and after exposure (normoxia: d = 0.7 [0.3, 1.2]; hypoxia: d = 1.3 [0.4, 2.3]). In conclusion, 2 weeks of normobaric hypoxia suppressed resting hepcidin levels, but did not alter the post‐exercise response in either normoxia or hypoxia, compared with the pre‐exposure response.

This study examined the test-retest reliability of near-infrared spectroscopy (NIRS), laser Doppler flowmetry (LDF) and Doppler ultrasound to assess exercise-induced haemodynamics. Nine men completed two identical trials consisting of 25-min submaximal cycling at first ventilatory threshold followed by repeated 30-s bouts of high-intensity (90% of peak power) cycling in 32.8 ± 0.4°C and 32 ± 5% relative humidity (RH). NIRS (tissue oxygenation index [TOI] and total haemoglobin [tHb]) and LDF (perfusion units [PU]) signals were monitored continuously during exercise, and leg blood flow was assessed by Doppler ultrasound at baseline and after exercise. Cutaneous vascular conductance (CVC; PU/mean arterial pressure (MAP)) was expressed as the percentage change from baseline (%CVCBL). Coefficients of variation (CVs) as indicators of absolute reliability were 18.7–28.4%, 20.2–33.1%, 42.5–59.8%, 7.8–12.4% and 22.2–30.3% for PU, CVC, %CVCBL, TOI and tHb, respectively. CVs for these variables improved as e...

Hughes, LJ, Banyard, HG, Dempsey, AR, Peiffer, JJ, and Scott, BR. Using load-velocity relationships to quantify training-induced fatigue. J Strength Cond Res 33(3): 762-773, 2019-The purpose of this study was to investigate using load-velocity relationships to quantify fluctuations in maximal strength (1 repetition maximum [1RM]), which occur as a result of training-induced fatigue. The 19 well-trained men (age: 24.3 ± 2.9 years, height: 180.1 ± 5.9 cm, body mass: 84.2 ± 10.5 kg, and squat 1RM: 151.1 ± 25.7 kg) who were recruited for this study attended 5 sessions. After baseline strength testing, individual load-velocity relationships were established using mean concentric velocity during visits 2, 4, and 5, with visit 3 consisting of a bout of fatiguing exercise (5 sets of squats performed to muscular failure with 70% 1RM). Predicted 1RM values were calculated using the minimal velocity threshold (1RMMVT), load at zero velocity (1RMLD0), and force-velocity (1RMFV) methods. Measured 1RM, maximal voluntary contractions, and perceived muscle soreness were used to examine the effects of fatigue in relation to the predicted 1RM scores. The 1RMMVT and 1RMLD0 demonstrated very strong and strong correlations with measured 1RM during each of the sessions (r = 0.90-0.96 and r = 0.77-0.84, respectively), while no strong significant correlations were observed for the 1RMFV. Further analysis using Bland-Altman plots demonstrated substantial interindividual variation associated with each method. These results suggest that load-velocity-based 1RM predictions are not accurate enough to be used for daily training load prescription, as has been previously suggested. Nevertheless, these predictions are practical to implement during an individual's warm-up and may be useful to indicate general fluctuations in performance potential, particularly if used in conjunction with other common monitoring methods.

Several prospective cohort studies have reported an association between higher levels of physical activity and decreased risk of cognitive decline and dementia, years later. To support physical activity as a preventative measure against dementia, including Alzheimer's disease (AD; the most common form of dementia), evidence regarding the underlying mechanisms is vital. Here, we review previous work examining the role of physical activity in modulating levels of AD pathological hallmarks, beta-amyloid (Aβ) and tau (in the brain, cerebrospinal fluid and blood). Robust evidence from transgenic animal studies suggests that physical activity (voluntary wheel running) and exercise (forced wheel running) are implicated in lowering levels of brain Aβ and tau. Nevertheless, evidence from human studies, utilising measurements from positron emission tomography and cerebrospinal fluid biomarkers, is less consistent. Rigorous randomised controlled trials utilising long exercise interventions are vital to further understand the relationship between physical activity and Alzheimer's disease.

Summary The combination of AMD3100 and low-dose FK506 has been shown to accelerate wound healing in vivo. Although AMD3100 is known to work by releasing hematopoietic stem cells into circulation, the mechanism of FK506 in this setting has remained unknown. In this study, we investigated the activities of FK506 in human cells and a diabetic-rat wound model using a non-immunosuppressive FK506 analog named FKVP. While FKVP was incapable of inhibiting calcineurin, wound-healing enhancement with AMD3100 was unaffected. Further study showed that both FK506 and FKVP activate BMP signaling in multiple cell types through FKBP12 antagonism. Furthermore, selective inhibition of BMP signaling abolished stem cell recruitment and wound-healing enhancement by combination treatment. These results shed new light on the mechanism of action of FK506 in acceleration of wound healing, and raise the possibility that less toxic FKBP ligands such as FKVP can replace FK506 for the treatment of chronic wounds.

Introduction: Blood flow restriction (BFR) during low-load resistance exercise increases muscle size similarly to high-load training, and may be an alternative to lifting heavy weights for older people at risk of sarcopenia. However, few studies have addressed the safety of such exercise in older people, or whether this is impacted by the actual exercises performed during training. This study aimed to compare the acute hemodynamic and perceptual responses during low-load BFR exercise to unrestricted low-load and high-load exercise in older women, and to determine whether these responses depend on the type of exercise performed. Methods: Fifteen older women (63–75 year) were assessed for maximal strength (1RM) in the leg press and leg extension. Participants then completed three protocols using these exercises in a randomized order: (1) low-load exercise (LL); (2) low-load exercise with BFR (LLBFR), and; (3) high-load exercise (HL). Blood pressure was assessed at baseline and after each set, and impedance cardiography measured cardiovascular function during trials. Rating of perceived exertion (RPE) and muscle soreness scores were obtained throughout trials. Results: Baseline hemodynamic values were consistent between trials. Systolic, diastolic, and mean arterial pressures were higher in LLBFR compared with HL and LL (p ≤ 0.021). The LL condition resulted in lower heart rate (p ≤ 0.002) and rate-pressure product (p ≤ 0.011) responses compared with LLBFR and HL. The leg press generally conferred greater hemodynamic and perceptual demands than the leg extension for all conditions (p ≤ 0.002). RPE was lower during LL compared with LLBFR and HL (p ≤ 0.008), and there were no between-condition differences in perceived muscle soreness. Conclusion: The blood pressure data indicate that LLBFR causes greater stress on the vasculature than LL and HL exercise, and that the leg press was generally more demanding than the leg extension. While additional cardiovascular measures were similar between LLBFR and HL conditions, caution should be advised when prescribing BFR exercise for individuals with compromised cardiac or vascular function. Nevertheless, LLBFR and HL exercise were perceived similarly, indicating that BFR training may be viable for healthy older people.

Purpose: To examine the effect of environmental temperature (TA) on performance and physiological responses (eg, body temperature, cardiopulmonary measures) during a high-intensity aerobic interval session. It was hypothesized that power output would be highest in the 13°C condition and lower in the 5°C, 22°C, and 35°C conditions. Methods: Eleven well-trained cyclists randomly completed 4 interval sessions at 5°C, 13°C, 22°C, and 35°C (55% [13%] relative humidity), each involving five 4-min intervals interspersed with 5 min of recovery. During the intervals, power output, core temperature (TC), skin temperature, VO2, and heart rate were recorded. Results: Mean session power output for 13°C (366 [32] W) was not higher than 5°C (363 [32] W; P = 1.00, effect size = 0.085), 22°C (364 [36] W; P = 1.00, effect size = 0.061), or 35°C (352 [31] W; P = .129, effect size = 0.441). The 5th interval of the 35°C condition had a lower power output compared with all other TA. TC was higher in 22°C compared with both 5°C and 13°C (P = .001). VO2 was not significantly different across TA (P = .187). Heart rate was higher in the 4th and 5th intervals of 35°C compared with 5°C and 13°C. Conclusions: This study demonstrates that while mean power outputs for intervals are similar across TA, hot TA (≥35°C) reduces interval power output later in a training session. Well-trained cyclists performing maximal high-intensity aerobic intervals can achieve near-optimal power output over a broader range of TA than previous literature would indicate.

Higher cardiorespiratory fitness has been associated with better cognitive function in older adults; yet, this relationship demonstrates a degree of variability across the older adult population. Thus, it is hypothesised that variation in genetic factors may influence the relationship between fitness and cognitive health. One such genetic factor is the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, which has previously been shown to moderate the relationship between self-reported physical activity and memory performance. In this study we aim to investigate the interaction between BDNF Val66Met polymorphism and objectively-measured cardiorespiratory fitness on performance on tasks assessing verbal and visuospatial memory. Data from ninety-nine cognitively normal men and women aged 60–80 years were used. Fitness was assessed by peak oxygen consumption, and verbal and visuospatial memory were evaluated using well-validated measures. Participants were categorised into: lower-fit Met carriers, higher-fit Met carriers, lower-fit Val/Val, or higher-fit Val/Val. Higher-fit individuals performed better on a task assessing visuospatial memory, compared with lower-fit individuals. Furthermore, an interaction between BDNF Val66Met and fitness was observed in terms of visuospatial memory performance on a continuous paired associate learning task; whereby lower-fit Met carriers performed 1 standard deviation worse than higher-fit Met carriers. No differences were observed between the higher-fit and lower-fit Val/Val homozygotes. Future intervention studies should evaluate the effect of structured exercise on cognitive health between BDNF Val66Met carriers and Val/Val homozygotes.

Higher cardiorespiratory fitness has been associated with enhanced cognitive function in older adults; yet, this relationship demonstrates a degree of variability. Thus, it is hypothesised that variation in genetic factors may influence the relationship between fitness and cognitive health. In this study we evaluate whether the BDNF Val66Met polymorphism moderates the relationship between cardiorespiratory fitness and verbal and visuospatial memory. Data from ninety-nine cognitively normal men and women aged 60 – 80 years were used. Fitness was assessed by peak oxygen consumption, and verbal and visuospatial memory were evaluated using well-validated measures. Participants were categorised into: lower-fit Met carriers, higher-fit Met carriers, lower-fit Val/Val, or higher-fit Val/Val. A significant interaction was observed between BDNF Val66Met and fitness on visuospatial memory performance; whereby lower-fit Met carriers performed 1SD lower than higher-fit Met carriers (p=0.04). We observed higher levels of fitness mitigated the deleterious effect of BDNF Met allele carriage on visuospatial memory. Future intervention studies should evaluate the effect of structured exercise on cognitive health between BDNF Val66Met carriers and Val/Val homozygotes.

Purpose:To examine the effect of postexercise cold-water immersion (CWI) protocols, compared with control (CON), on the magnitude and time course of core temperature (Tc) responses.Methods:Pooled-data analyses were used to examine theTcresponses of 157 subjects from previous postexercise CWI trials in the authors’ laboratories. CWI protocols varied with different combinations of temperature, duration, immersion depth, and mode (continuous vs intermittent).Tcwas examined as a double difference (ΔΔTc), calculated as the change inTcin CWI condition minus the corresponding change in CON. The effect of CWI on ΔΔTcwas assessed using separate linear mixed models across 2 time components (component 1, immersion; component 2, postintervention).Results:Intermittent CWI resulted in a mean decrease in ΔΔTcthat was 0.25°C (0.10°C) (estimate [SE]) greater than continuous CWI during the immersion component (P = .02). There was a significant effect of CWI temperature during the immersion component (P = .05), where reductions in water temperature of 1°C resulted in decreases in ΔΔTcof 0.03°C (0.01°C). Similarly, the effect of CWI duration was significant during the immersion component (P = .01), where every 1 min of immersion resulted in a decrease in ΔΔTcof 0.02°C (0.01°C). The peak difference inTcbetween the CWI and CON interventions during the postimmersion component occurred at 60 min postintervention.Conclusions:Variations in CWI mode, duration, and temperature may have a significant effect on the extent of change inTc. Careful consideration should be given to determine the optimal amount of core cooling before deciding which combination of protocol factors to prescribe.

What is the central question of this study? Does 14 days of live-high, train-low simulated altitude alter an individual's metabolomic/metabolic profile? What is the main finding and its importance? This study demonstrated that ∼200 h of moderate simulated altitude exposure resulted in greater variance in measured metabolites between subject than within subject, which indicates individual variability during the adaptive phase to altitude exposure. In addition, metabolomics results indicate that altitude alters multiple metabolic pathways, and the time course of these pathways is different over 14 days of altitude exposure. These findings support previous literature and provide new information on the acute adaptation response to altitude.The purpose of this study was to determine the influence of 14 days of normobaric hypoxic simulated altitude exposure at 3000 m on the human plasma metabolomic profile. For 14 days, 10 well-trained endurance runners (six men and four women; 29 ± 7 years of age) lived at 3000 m simulated altitude, accumulating 196.4 ± 25.6 h of hypoxic exposure, and trained at ∼600 m. Resting plasma samples were collected at baseline and on days 3 and 14 of altitude exposure and stored at -80°C. Plasma samples were analysed using liquid chromatography-high-resolution mass spectrometry to construct a metabolite profile of altitude exposure. Mass spectrometry of plasma identified 36 metabolites, of which eight were statistically significant (false discovery rate probability 0.1) from baseline to either day 3 or day 14. Specifically, changes in plasma metabolites relating to amino acid metabolism (tyrosine and proline), glycolysis (adenosine) and purine metabolism (adenosine) were observed during altitude exposure. Principal component canonical variate analysis showed significant discrimination between group means (P 0.05), with canonical variate 1 describing a non-linear recovery trajectory from baseline to day 3 and then back to baseline by day 14. Conversely, canonical variate 2 described a weaker non-recovery trajectory and increase from baseline to day 3, with a further increase from day 3 to 14. The present study demonstrates that metabolomics can be a useful tool to monitor metabolic changes associated with altitude exposure. Furthermore, it is apparent that altitude exposure alters multiple metabolic pathways, and the time course of these changes is different over 14 days of altitude exposure.

This study examined the effect of 2 forms of exercise on glucose tolerance and the concurrent changes in markers associated with the interleukin (IL)-6 pathways. Fifteen sedentary, overweight males (29.0 ± 3.1 kg/m2) completed 2 separate, 3-day trials in randomised and counterbalanced order. An oral glucose tolerance test (OGTT; 75 g) was performed at the same time on each day of the trial. Day 2 of each trial consisted of a single 30-min workload-matched bout of either high-intensity intermittent exercise (HIIE; alternating 100% and 50% of peak oxygen uptake) or continuous moderate-intensity exercise (CME; 60 % of peak oxygen uptake) completed 1 h prior to the OGTT. Venous blood samples were collected before, immediately after, 1 h after, and 25 h after exercise for measurement of insulin, C-peptide, IL-6, and the soluble IL-6 receptors (sIL-6R; soluble glycoprotein 130 (sgp130)). Glucose area under the curve (AUC) was calculated from capillary blood samples collected throughout the OGTT. Exercise resulted in a modest (4.4%; p = 0.003) decrease in the glucose AUC when compared with the pre-exercise AUC; however, no differences were observed between exercise conditions (p = 0.65). IL-6 was elevated immediately after and 1 h after exercise, whilst sgp130 and sIL-6R concentrations were reduced immediately after exercise. In summary, exercise was effective in reducing glucose AUC, which was attributed to improvements that took place between 60 and 120 min into the OGTT, and was in parallel with an increased ratio of IL-6 to sIL-6R, which accords with an increased activation via the “classical” IL-6 signalling pathway. Our findings suggest that acute HIIE did not improve glycaemic response when compared with CME.

Ratings of perceived exertion (RPE) and effort are considered extremely important in the regulation of intensity during self-paced physical activity. While effort and exertion are slightly different constructs, these terms are often used interchangeably within the literature. The development of perceptions of both effort and exertion is a complicated process involving numerous neural processes occurring in various regions within the brain. It is widely accepted that perceptions of effort are highly dependent on efferent copies of central drive which are sent from motor to sensory regions of the brain. Additionally, it has been suggested that perceptions of effort and exertion are integrated based on the balance between corollary discharge and actual afferent feedback; however, the involvement of peripheral afferent sensory feedback in the development of such perceptions has been debated. As such, this review examines the possible difference between effort and exertion, and the implications of such differences in understanding the role of such perceptions in the regulation of pace during exercise.

This study compared the effect of passive rest (CON) and water immersion at 8.6±0.2°C (CWI9), 14.6±0.3°C (CWI15) and 35.0±0.4°C (thermoneutral water immersion [TWI]) on post-exercise heart rate variability (HRV) indices. In a climate chamber (32.8±0.4°C, 32±5% relative humidity), nine men completed 25 min of cycling at the first ventilatory threshold and repeated 30-second bouts at 90% of peak power followed by a 5-minute recovery treatment in a randomised crossover manner. All water immersion re-established the HRV indices (natural logarithm of the square root of the mean sum squared differences between RR intervals [ln rMSSD], low-frequency [lnLF] and high-frequency power densities [lnHF] and Poincaré plotderived measures [lnSD1 and lnSD2]) to the pre-exercise levels at 60 min post immersion; however, only CWI9 accelerated parasympathetic reactivation during immersion. CWI9 increased lnLF and lnSD2 during immersion when compared with CON (p0.80) on all HRV indices during immersion when compared with CON, between-conditions differences were observed only in lnLF and lnSD2 (p=.017-.023). CWI15 had a large positive ES on ln rMSSD and lnSD1 when compared with CON (both p=.064). Sympathovagal antagonism (i.e., SD ratio

Context: Night games are a regular occurrence for team-sport athletes, yet sleep complaints following night competitions are common. The mechanisms responsible for reported sleep difficulty in athletes are not understood. Methods: An observational crossover design investigating a night netball game and a time-matched rest day in 12 netball athletes was conducted to ascertain differences in physiological (core temperature), psychometric (state and trait), and neuroendocrine (adrenaline, noradrenaline, and cortisol) responses. Results: Following the night game, athletes experienced reduced sleep durations, lower sleep efficiency, early awakenings, and poorer subjective sleep ratings compared with the rest day. No differences were found between core temperature, state psychometric measures, and cortisol at bedtime. Adrenaline and noradrenaline concentrations were elevated compared with the time-matched rest day prior to (26.92 [15.88] vs 12.90 [5.71] and 232.6 [148.1] vs 97.83 [36.43] nmol/L, respectively) and following the night game (18.67 [13.26] vs 11.92 [4.56] and 234.1 [137.2] vs 88.58 [54.08] nmol/L, respectively); however, the concentrations did not correlate to the sleep variables (duration, efficiency, and sleep-onset latency). A correlation (rs = −.611) between sleep efficiency and hyperarousal (trait psychometric measure) was found. Conclusions: Athletes experienced poor sleep following a night game. Furthermore, results suggest that athletes who have a tendency toward a high trait arousal may be more susceptible to sleep complaints following a night game. These data expand knowledge and refute frequently hypothesized explanations for poor sleep following night competition. The results may also help support staff and coaches target strategies for individual athletes at a higher risk of sleep complaints.

This review evaluated the effects of precooling via cold water immersion (CWI) and ingestion of ice slurry/slushy or crushed ice (ICE) on endurance performance measures (e.g. time-to-exhaustion and time trials) and psychophysiological parameters (core [T

Introduction Inconsistent results from previous studies of exercise and cognitive function suggest that rigorously designed randomized controlled trials are urgently needed. Here, we describe the design of the Intense Physical Activity and Cognition (IPAC) study, which will assess the impact of a 6-month high-intensity exercise intervention on cognitive function and biomarkers of dementia risk, compared with a 6-month moderate-intensity exercise intervention and control group (no study-related exercise). Methods One-hundred and five cognitively healthy men and women aged between 60 and 80 years are randomized into a high-intensity exercise, moderate-intensity exercise, or control group. Individuals randomized to an exercise intervention undertake 6 months of cycle-based exercise twice a week, at 50 minutes per session. All participants undergo comprehensive neuropsychological testing, blood sampling, brain magnetic resonance imaging, fitness testing, and a body composition scan at baseline, 6 months (immediately after intervention), and 18 months (12 months after intervention). Discussion The IPAC study takes a multidisciplinary approach to investigating the role of exercise in maintaining a healthy brain throughout aging. Rigorous monitoring of exertion and adherence throughout the intervention, combined with repeated measures of fitness, is vital in ensuring an optimum exercise dose is reached. Results from the IPAC study will be used to inform a large-scale multicentre randomized controlled trial, with the ultimate aim of pinpointing the frequency, duration, and intensity of exercise that provides the most benefit to the brain, in terms of enhancing cognitive function and reducing dementia risk in older adults.

Introduction The objective of this study was to evaluate the relationship between self-reported exercise levels and Alzheimer's disease (AD) biomarkers, in a cohort of autosomal dominant AD mutation carriers. Methods In 139 presymptomatic mutation carriers from the Dominantly Inherited Alzheimer Network, the relationship between self-reported exercise levels and brain amyloid load, cerebrospinal fluid (CSF) Aβ 42, and CSF tau levels was evaluated using linear regression. Results No differences in brain amyloid load, CSF Aβ 42 , or CSF tau were observed between low and high exercise groups. Nevertheless, when examining only those already accumulating AD pathology (i.e., amyloid positive), low exercisers had higher mean levels of brain amyloid than high exercisers. Furthermore, the interaction between exercise and estimated years from expected symptom onset was a significant predictor of brain amyloid levels. Discussion Our findings indicate a relationship exists between self-reported exercise levels and brain amyloid in autosomal dominant AD mutation carriers.

A large body of epidemiological and experimental data exploring the relationship between physical activity (PA) and Alzheimer’s disease (AD) are now available. Despite observational evidence supporting a role for PA in delaying the onset of AD, randomised controlled trials have reported mixed findings, likely due to the heterogeneity in study cohorts, outcome measures, and the adopted PA intervention. The primary objective of this narrative review is to evaluate the extant evidence on the relationship between PA, cognitive decline and AD in older populations. The interaction between PA and the putative mechanisms underlying AD progression, including genetic factors and amyloid-β levels will be explored. In this context, particular attention will be given to studies assessing PA in the early clinical and preclinical, asymptomatic stages of AD. Based on current evidence, clinical considerations for implementation of exercise-based interventions are discussed, along with limitations of previous research and directions for future studies.

Objectives Blood flow restriction (BFR) during interval cycling may stimulate aerobic and anaerobic adaptations. However, acute physiological responses to BFR interval cycling have not been extensively investigated. Design Eighteen males completed low-intensity (LI), low-intensity with BFR (LIBFR) and high-intensity (HI) interval cycling sessions in randomised and counterbalanced order. These included a standardised warm-up and three two-min intervals interspersed with two-min recovery. Interval intensity during HI, LI and LIBFR were 85%, 40% and 40% of peak power output obtained during graded exercise tests. Methods During LIBFR, 80% arterial occlusion was applied to both legs during the interval efforts and removed during recovery. Continuous measures of heart rate (HR), cardiac output (CO) and oxygen consumption (View the MathML sourceV˙O2) were recorded. Blood pressure (BP) and rating of perceived exertion (RPE) were measured following intervals. Blood lactate concentration was measured pre- and post-exercise. Results BP, HR, CO, View the MathML sourceV˙O2, lactate and RPE were greatest during HI. During the active intervals, BP, HR and CO were greater during LIBFR than LI. View the MathML sourceV˙O2 during recovery periods were greater in LIBFR than LI. Post-session lactate was greater during LIBFR than LI. Importantly, mean arterial pressure during interval three was significantly greater in LIBFR (124 ± 2 mmHg) than HI (114 ± 3 mmHg). Conclusions LIBFR increases cardiovascular and metabolic stress compared with LI and could provide an alternative aerobic training method for individuals unable to perform high-intensity exercise. However, increases in mean arterial pressure during LIBFR indicates high myocardial workload, and practitioners should therefore use caution if prescribing LIBFR for vascular compromised individuals.

Epstein-Barr virus (EBV) is a ubiquitous human gammaherpesvirus that establishes a latency reservoir in B cells. In this work, we show that ibrutinib, idelalisib, and dasatinib, drugs that block B cell receptor (BCR) signaling and are used in the treatment of hematologic malignancies, block BCR-mediated lytic induction at clinically relevant doses. We confirm that the immunosuppressive drugs cyclosporine and tacrolimus also inhibit BCR-mediated lytic induction but find that rapamycin does not inhibit BCR-mediated lytic induction. Further investigation shows that mammalian target of rapamycin complex 2 (mTORC2) contributes to BCR-mediated lytic induction and that FK506-binding protein 12 (FKBP12) binding alone is not adequate to block activation. Finally, we show that BCR signaling can activate EBV lytic induction in freshly isolated B cells from peripheral blood mononuclear cells (PBMCs) and that activation can be inhibited by ibrutinib or idelalisib. IMPORTANCE EBV establishes viral latency in B cells. Activation of the B cell receptor pathway activates lytic viral expression in cell lines. Here we show that drugs that inhibit important kinases in the BCR signaling pathway inhibit activation of lytic viral expression but do not inhibit several other lytic activation pathways. Immunosuppressant drugs such as cyclosporine and tacrolimus but not rapamycin also inhibit BCR-mediated EBV activation. Finally, we show that BCR activation of lytic infection occurs not only in tumor cell lines but also in freshly isolated B cells from patients and that this activation can be blocked by BCR inhibitors.

Scott, BR, Peiffer, JJ, and Goods, PSR. The effects of supplementary low-load blood flow restriction training on morphological and performance-based adaptations in team sport athletes. J Strength Cond Res 31(8): 2147-2154, 2017-Low-load resistance training with blood flow restriction (BFR) may be a method to enhance muscular development even in trained athletes. This study aimed to assess whether supplemental low-load BFR training can improve muscle size, strength, and physical performance characteristics in team sport athletes. Twenty-one semiprofessional Australian football athletes were assessed for 3-repetition maximum (3RM) and muscular endurance in the back squat, vastus lateralis muscle architecture, and performance in sprint and vertical jump tasks. Participants then undertook a 5-week training program, consisting of normal high-load resistance training supplemented by low-load squats with (LLBFR) or without (LL) BFR. Participants also performed regular conditioning and football training during this period. After the training intervention, participants again completed the pretraining testing battery. Squat 3RM and endurance increased from pretraining levels in both LL (3RM = 12.5% increase; endurance = 24.1% increase; p ≤ 0.007) and LLBFR (3RM = 12.3% increase; endurance = 21.2% increase; p = 0.007) groups, though there were no between-group differences. No post-training changes were observed for muscle architecture, or performance in sprinting and jumping tasks. Although squat 3RM and endurance performance increased in both groups, adding BFR during supplemental exercise did not enhance these responses. Similarly, there were no large differences in the assessments of sprint, acceleration, and jumping performance between the groups after training. These findings suggest that although LLBFR did not negatively affect adaptive responses to resistance training, this training strategy may not provide added benefit for healthy Australian football athletes already undertaking a rigorous training schedule.

Cet article traite de la facon dont certains scientifiques de la periode precedant la seconde guerre mondiale ont utilise un programme d'euthanasie, provoquant la mort de milliers d'enfants handicapes et d'adultes pour beneficier d'une matiere propice au developpement de leurs recherches. La valeur scientifique de ces recherches et un jugement ethique sur ces agissements sont ici clairement exposes

Objectives: The objective of this study to report on the development and psychometric analysis of a scale to measure post exercise exhaustion. Design: This study utilised the Rasch measurement model for the psychometric analysis of a new scale aimed at measuring acute onset exhaustion in athletes. Method: An extensive literature review, feedback from athletes and an expert panel from educators in psychology, sports science and exercise physiology provided feedback on the scale, providing evidence of content validity. A final survey, consisting of the 25 items and completed by three hundred and seventynine athletes (Sport: 187 tri-athletes and 192 cyclists; gender: 211 males, and 168 females; age: 18e25 [31], 26e35 [114], 36e45 [120], and 46þ [114]), was submitted to Rasch analysis. Results: After amendments a final 14 item scale provided internally consistent and reliable measures of exhaustion for participants. The items of the final scale have good fit, and the scale has high PSI providing statistical evidence of reliability. The scale could benefit from items dealing with mid-range levels of exhaustion. The correlational association between the new scale and a similar scale was positive and significant correlation adding to the evidence of the validity of the new scale. Conclusions: The scale appears to be a valuable tool for the assessment of exercise-induced acute onset exhaustion and may be an attractive option for researchers, clinicians, and coaches seeking to measure the levels of exhaustion in individuals. In addition to its valid theoretical structure and sound psychometric properties, the scale has advantages over other exhaustion or fatigue scales as it is not disease-specific. © 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

Influence of contrast shower and water immersion on recovery in elite netballers. J Strength Cond Res 28(8): 2353–2358, 2014—Contrast water therapy is a popular recovery modality in sport; however, appropriate facilities can often be difficult to access. Therefore, the present study examined the use of contrast showers as an alternative to contrast water therapy for team sport recovery. In a randomized, crossover design, 10 elite female netball athletes (mean ± SD: age, 20 ± 0.6 years; height, 1.82 ± 0.05 m; body mass, 77.0 ± 9.3 kg) completed 3 experimental trials of a netball specific circuit followed by one of the following 14-minute recovery interventions: (a) contrast water therapy (alternating 1 minute 38° C and 1 minute 15° C water immersion), (b) contrast showers (alternating 1 minute 38° C and 1 minute 18° C showers), or (c) passive recovery (seated rest in 20° C). Repeated agility, skin and core temperature, and perception scales were measured before, immediately after, 5 and 24 hours postexercise. No significant differences in repeated agility were evident between conditions at any time point. No significant differences in core temperature were observed between conditions; however, skin temperature was significantly lower immediately after contrast water therapy and contrast showers compared with the passive condition. Overall perceptions of recovery were superior after contrast water therapy and contrast showers compared with passive recovery. The findings indicate contrast water therapy and contrast showers did not accelerate physical recovery in elite netballers after a netball specific circuit; however, the psychological benefit from both interventions should be considered when determining the suitability of these recovery interventions in team sport.

Two studies were conducted to examine the effects of ice slushy ingestion (ICE) and cold water immersion (CWI) on thermoregulatory and sweat responses during constant (study 1) and self-paced (study 2) exercise. In study 1, 11 men cycled at 40-50% of peak aerobic power for 60 min (33.2 ± 0.3°C, 45.9 ± 0.5% relative humidity, RH). In study 2, 11 men cycled for 60 min at perceived exertion (RPE) equivalent to 15 (33.9 ± 0.2°C and 42.5 ± 3.9%RH). In both studies, each trial was preceded by 30 min of CWI (~22°C), ICE or no cooling (CON). Rectal temperature (Tre), skin temperature (Tsk), thermal sensation, and sweat responses were measured. In study 1, ICE decreased Tre-Tsk gradient versus CON (p = 0.005) during first 5 min of exercise, while CWI increased Tre-Tsk gradient versus CON and ICE for up to 20 min during the exercise (p0.05). Increased Tre-Tsk gradient by CWI improved MPO while ICE reduced Tre but did not confer any ergogenic effect. Both precooling treatments attenuated the thermal efferent signals until a specific body temperature threshold was reached.

Juliff, LE, Halson, SL, Hebert, JJ, Forsyth, PL, and Peiffer, JJ. Longer sleep durations are positively associated with finishing place during a national multiday netball competition. J Strength Cond Res 32(1): 189-194, 2018-Sleep is often regarded as the single best recovery strategy available to an athlete, yet little is known about the quality and quantity of sleep in athletes during multiday competitions. This study objectively evaluated sleep characteristics of athletes during a national netball tournament. Using wrist actigraphy monitors and sleep diaries, 42 netballers from 4 state teams were monitored for the duration of a tournament (6 days) and 12 days before in home environments. Significant differences were found between teams based on final competition standings, suggesting enhanced sleep characteristics in athlete's whose team finished higher in the tournament standings. The top 2 placed teams when compared with the lower 2 placed teams slept longer (8:02 ± 36:43; 7:01 ± 27:33), had greater time in bed (9:03 ± 0:52; 7:59 ± 0:54) and reported enhanced subjective sleep ratings (2.6 ± 0.5; 2.3 ± 0.6). Sleep efficiency was no different between teams. A strong correlation (r = -0.68) was found indicating longer sleep durations during competition were associated with higher final tournament positions. Encouraging athletes to aim for longer sleep durations in competition, where possible, may influence the outcome in tournament style competitions.

Purpose:To examine the influence of manipulating aerobic contribution after whole-blood removal on pacing patterns, performance, and energy contribution during self-paced middle-distance cycling.Methods:Seven male cyclists (33 ± 8 y) completed an incremental cycling test followed 20 min later by a 4-min self-paced cycling time trial (4MMP) on 6 separate occasions over 42 d. The initial 2 sessions acted as familiarization and baseline testing, after which 470 mL of blood was removed, with the remaining sessions performed 24 h, 7 d, 21 d, and 42 d after blood removal. During all 4MMP trials, power output, oxygen uptake, and aerobic and anaerobic contribution to power were determined.Results:4MMP average power output significantly decreased by 7% ± 6%, 6% ± 8%, and 4% ± 6% at 24 h, 7 d, and 21 d after blood removal, respectively. Compared with baseline, aerobic contribution during the 4MMP was significantly reduced by 5% ± 4%, 4% ± 5%, and 4% ± 10% at 24 h, 7 d, and 21 d, respectively. The rate of decline in power output on commencement of the 4MMP was significantly attenuated and was 76% ± 20%, 72% ± 24%, and 75% ± 35% lower than baseline at 24 h, 21 d, and 42 d, respectively.Conclusion:Removal of 470 mL of blood reduces aerobic energy contribution, alters pacing patterns, and decreases performance during self-paced cycling. These findings indicate the importance of aerobic energy distribution during self-paced middle-distance events.

The invariance of the standard model (SM) under the CPT transformation predicts equality of particle and antiparticle masses. This prediction is tested by measuring the mass difference between the top quark and antiquark (Δmt=mt−mt‾) that are produced in pp collisions at a center-of-mass energy of 8 TeV, using events with a muon or an electron and at least four jets in the final state. The analysis is based on data corresponding to an integrated luminosity of 19.6 fb−1collected by the CMS experiment at the LHC, and yields a value of Δmt=−0.15±0.19(stat)±0.09(syst) GeV, which is consistent with the SM expectation. This result is significantly more precise than previously reported measurements. © 2017 The Author(s)

Purpose:To describe the within-season external workloads of professional male road cyclists for optimal training prescription.Methods:Training and racing of 4 international competitive professional male cyclists (age 24 ± 2 y, body mass 77.6 ± 1.5 kg) were monitored for 12 mo before the world team-time-trial championships. Three within-season phases leading up to the team-time-trial world championships on September 20, 2015, were defined as phase 1 (Oct–Jan), phase 2 (Feb–May), and phase 3 (June–Sept). Distance and time were compared between training and racing days and over each of the various phases. Times spent in absolute (500 W) and relative (0–1.9, 2.0–4.9, 5.0–7.9, >8 W/kg) power zones were also compared for the whole season and between phases 1–3.Results:Total distance (3859 ± 959 vs 10911 ± 620 km) and time (240.5 ± 37.5 vs 337.5 ± 26 h) were lower (P < .01) in phase 1 than phase 2. Total distance decreased (P < .01) from phase 2 to phase 3 (10911 ± 620 vs 8411 ± 1399 km, respectively). Mean absolute (236 ± 12.1 vs 197 ± 3 W) and relative (3.1 ± 0 vs 2.5 ± 0 W/kg) power output were higher (P < .05) during racing than training, respectively.Conclusion:Volume and intensity differed between training and racing over each of 3 distinct within-season phases.

Manual therapy is suggested as a potentially therapeutic intervention that may improve pulmonary function. However, this form of therapy is largely based on clinical observations and hypothetical models rather than mechanistic knowledge. This study examined the influence of a single session of manual therapy applied to the thoracic spine and thorax on dynamic pulmonary function over an extended time frame in healthy adults. 21 healthy individuals (14 males) aged 19–35 (mean [SD] age = 23 [3.9], BMI [SD] = 22.97 [2.41]) completed one experimental testing session consisting of five pulmonary function tests and the delivery of a manual therapy intervention. Pulmonary function was measured at baseline and 1 minute, 10 minutes, 20 minutes and 30 minutes following the intervention. Baseline mean (SD) forced vital capacity (FVC), forced expired volume in 1 second (FEV1) and maximal voluntary ventilation (MVV) were 5.55(1.23 L), 4.64(0.92 L) and 165.7(40.0L min−1) respectively. The mean (SD) FEV1/FVC ratio was 0.84(0.07). There were no statistically significant changes in any of the pulmonary function measures following the manual therapy intervention. Our findings do not support the use of manual therapy to provide a short-term benefit in respiratory function to healthy adults.

© 2017 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd This study assessed whether hypoxia during high-load resistance exercise could enhance the acute physiological responses related to muscular development. Twelve trained men performed exercise in three conditions: normoxia (fraction of inspired oxygen [FIO2] = 21%), moderate-level hypoxia (FIO2 = 16%) and high-level hypoxia (FIO2 = 13%). Exercise comprised high-load squats and deadlifts (5 × 5 using 80% of 1-repetition maximum with 180-s rest). Muscle oxygenation and activation were monitored during exercise. Metabolic stress was estimated via capillary blood sampling. Perceived fatigue and soreness were also quantified following exercise. While the hypoxic conditions appeared to affect muscle oxygenation, significant differences between conditions were only noted for maximal deoxyhaemoglobin in the deadlift (P = 0·009). Blood lactate concentration increased from 1·1 to 1·2 mmol l−1 at baseline to 9·5–9·8 mmol l−1 after squats and 10·4–10·5 mmol l−1 after deadlifts (P≤0·001), although there were no between-condition differences. Perceived fatigue and muscle soreness were significantly elevated immediately and at 24 h following exercise, respectively, by similar magnitudes in all conditions (P≤0·001). Muscle activation did not differ between conditions. While metabolic stress is thought to moderate muscle activation and subsequent muscular development during hypoxic resistance training, it is not augmented during traditional high-load exercise. This may be explained by the low number of repetitions performed and the long interset rest periods employed during this training. These findings suggest that high-load resistance training might not benefit from additional hypoxia as has been shown for low- and moderate-load training.

Objectives: Research is equivocal regarding endurance performance benefits of external nasal dilators, and currently research focusing on internal nasal dilators is non-existent. Both devices are used within competitive cycling. This study examined the influence of external and internal nasal dilation on cycling economy of motion and 20-km time trial performance. Design: The study utilized a randomized, counterbalanced cross-over design. Methods: Fifteen trained cyclists completed three exercise sessions consisting of a 15min standardized warm up and 20-km cycling time trial while wearing either a Breathe Right® external nasal dilator, Turbine® internal nasal dilator or no device (control). During the warm up, heart rate, ratings of perceived exertion and dyspnea and expired gases were collected. During the time trial, heart rate, perceived exertion, and dyspnea were collected at 4-km intervals and mean 20-km power output was recorded. Results: No differences were observed for mean 20-km power output between the internal (270. ±. 45. W) or external dilator (271. ±. 44. W) and control (272. ±. 44. W). No differences in the economy of motion were observed throughout the 15-min warm up between conditions. Conclusions: The Turbine® and Breathe Right® nasal dilators are ineffective at enhancing 20-km cycling time trial performance.

Purpose:To investigate the effect of 3 swim-pacing profiles on subsequent performance during a sprint-distance triathlon (SDT). Methods:Nine competitive/trained male triathletes completed 5 experimental sessions including a graded running exhaustion test, a 750-m swim time trial (STT), and 3 SDTs. The swim times of the 3 SDTs were matched, but pacing was manipulated to induce positive (ie, speed gradually decreasing from 92% to 73% STT), negative (ie, speed gradually increasing from 73% to 92% STT), or even pacing (constant 82.5% STT). The remaining disciplines were completed at a self-selected maximal pace. Speed over the entire triathlon, power output during the cycle discipline, rating of perceived exertion (RPE) for each discipline, and heart rate during the cycle and run were determined. Results:Faster cycle and overall triathlon times were achieved with positive swim pacing (30.5 ± 1.8 and 65.9 ± 4.0 min, respectively), as compared with the even (31.4 ± 1.0 min, P = .018 and 67.7 ± 3.9 min, P = .034, effect size [ES] = 0.46, respectively) and negative (31.8 ± 1.6 min, P = .011 and 67.3 ± 3.7 min, P = .041, ES = 0.36, respectively) pacing. Positive swim pacing elicited a lower RPE (9 ± 2) than negative swim pacing (11 ± 2, P = .014). No differences were observed in the other measured variables. Conclusions:A positive swim pacing may improve overall SDT performance and should be considered by both elite and age-group athletes during racing.

Western countries are experiencing aging populations and increased longevity; thus, the incidence of dementia and Alzheimer's disease (AD) in these countries is projected to soar. In the absence of a therapeutic drug, non-pharmacological preventative approaches are being investigated. One of these approaches is regular participation in physical activity or exercise. This paper reviews studies that have explored the relationship between physical activity and cognitive function, cognitive decline, AD/dementia risk and AD-associated biomarkers and processes. There is now strong evidence that links regular physical activity or exercise to higher cognitive function, decreased cognitive decline and reduced risk of AD or dementia. Nevertheless, these associations require further investigation, more specifically with interventional studies that include long follow-up periods. In particular, relatively little is known about the underlying mechanism(s) of the associations between physical activity and AD neuropathology; clearly this is an area in need of further research, particularly in human populations. Although benefits of physical activity or exercise are clearly recognised, there is a need to clarify how much physical activity provides the greatest benefit and also whether people of different genotypes require tailored exercise regimes.

Purpose:Manufacturers of uncoupled cycling cranks claim that their use will increase economy of motion and gross efficiency. Purportedly, this occurs by altering the muscle-recruitment patterns contributing to the resistive forces occurring during the recovery phase of the pedal stroke. Uncoupled cranks use an independent-clutch design by which each leg cycles independently of the other (ie, the cranks are not fixed together). However, research examining the efficacy of training with uncoupled cranks is equivocal. The purpose of this study was to determine the effect of short-term training with uncoupled cranks on the performance-related variables economy of motion, gross efficiency, maximal oxygen uptake (VO2max), and muscle-activation patterns.Methods:Sixteen trained cyclists were matched-paired into either an uncoupled-crank or a normal-crank training group. Both groups performed 5 wk of training on their assigned cranks. Before and after training, participants completed a graded exercise test using normal cranks. Expired gases were collected to determine economy of motion, gross efficiency, and VO2max, while integrated electromyography (iEMG) was used to examine muscle-activation patterns of the vastus lateralis, biceps femoris, and gastrocnemius.Results:No significant changes between groups were observed for economy of motion, gross efficiency, VO2max, or iEMG in the uncoupled- or normal-crank group.Conclusions:Five weeks of training with uncoupled cycling cranks had no effect on economy of motion, gross efficiency, muscle recruitment, or VO2max compared with training on normal cranks.

This study examined the relationship between intensity of training and changes in hydration status, core temperature, sweat rate and composition and fluid balance in professional football players training in the heat. Thirteen professional football players completed three training sessions; "higher-intensity" (140 min; HI 140), "lower-intensity" (120 min; LI 120) and "game-simulation" (100 min; GS 100). Movement demands were measured by Global Positioning System, sweat rate and concentration were determined from dermal patches and body mass change. Despite similar environmental conditions (26.9 ± 0.1°C and 65.0 ± 7.0% relative humidity [Rh]), higher relative speeds (m · min -1) and increased perceptions of effort and thermal strain were observed in HI 140 and GS 100 compared with LI 120 (P < 0.05). Significantly (P < 0.05) greater sweat rate (L · h -1) and electrolyte losses (g) were observed in HI 140 and GS 100 compared with LI 120. Rate of rise in core temperature was correlated with mean speed (r = 0.85), session rating of perceived exertion (sRPE) (r = 0.61), loss of potassium (K +) (r = 0.51) sweat rate (r = 0.49), and total sweat loss (r = 0.53), with mean speed the strongest predictor. Sodium (Na +) (r = 0.39) and K + (r = 0.50) losses were associated with total distance covered. In hot conditions, individualised rehydration practices should be adopted following football training to account for differences in sweat rate and electrolyte losses in response to intensity and overall activity within a session. © 2012 Copyright Taylor and Francis Group, LLC.

Single-leg cycling may enhance the peripheral adaptations of skeletal muscle to a greater extent than double-leg cycling. The purpose of the current study was to determine the influence of 3 wk of high-intensity single- and double-leg cycle training on markers of oxidative potential and muscle metabolism and exercise performance. In a crossover design, nine trained cyclists (78 ± 7 kg body wt, 59 ± 5 ml·kg−1·min−1maximal O2consumption) performed an incremental cycling test and a 16-km cycling time trial before and after 3 wk of double-leg and counterweighted single-leg cycle training (2 training sessions per week). Training involved three (double) or six (single) maximal 4-min intervals with 6 min of recovery. Mean power output during the single-leg intervals was more than half that during the double-leg intervals (198 ± 29 vs. 344 ± 38 W, P < 0.05). Skeletal muscle biopsy samples from the vastus lateralis revealed a training-induced increase in Thr172-phosphorylated 5′-AMP-activated protein kinase α-subunit for both groups ( P < 0.05). However, the increase in cytochrome c oxidase subunits II and IV and GLUT-4 protein concentration was greater following single- than double-leg cycling ( P < 0.05). Training-induced improvements in maximal O2consumption (3.9 ± 6.2% vs. 0.6 ± 3.6%) and time-trial performance (1.3 ± 0.5% vs. 2.3 ± 4.2%) were similar following both interventions. We conclude that short-term high-intensity single-leg cycle training can elicit greater enhancement in the metabolic and oxidative potential of skeletal muscle than traditional double-leg cycling. Single-leg cycling may therefore provide a valuable training stimulus for trained and clinical populations.