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Hypobaria and hypoxia exert independent effects on oxidative stress during exercise, while combined effectson the post-exercise recovery period remain unclear.Accordingly, this study examined the recovery period during lab-simulated hypoxic and hypobaric conditions following exercise-induced oxidative stress. Participants (n=13) performed 60-minutes of cycling (70% watts max) in a normobaric normoxic environment followed by a four-hour recovery under three conditions; 1000m normobaric normoxia (NN, 675mmHg), 4400m normobaric hypoxia (NH, 675mmHg), or 4400m hypobaric hypoxia (HH, 440mmHg). Blood samples collected at Pre, Post, 2-Hours (2-HR), and 4-Hours (4-HR) post-exercise were analyzed fora potential increase in biochemical modifications of proteins(protein carbonyls, PC; 3-nitrotyrosines, 3NT) lipids (lipid hydroperoxides, LOOH; 8-isoprostanes, 8-ISO), and antioxidant capacity (FRAP, TEAC). Gene transcripts (EPAS, HMOX1, SOD2, NFE2L2) were quantified by qRT-PCR from muscle biopsies taken Pre and Post exercise. Hypoxia and hypobaria had no effect throughout recovery. Post-exercise TEAC (p=0.041), FRAP (p=0.013), and 8-ISO (p=0.044) increased, while PC (p=0.002) and 3-NT (p=0.032) were decreased. LOOH was lower in Post (p=0.018) NH trial samples. Exercise-dependent increases occurred in NFE2L2 (p=0.003), HMXO1 (p0.001), SOD2 (p=0.046), and EPAS (p=0.038). Exercise recovery under conditions of NH and HH did not impact blood oxidative stress or redox-sensitive gene transcripts.

ObjectivesInforming research participants of the results of studies in which they took part is viewed as an ethical imperative. However, there is little guidance in the literature about how to do this. The Fluoxetine Or Control Under Supervision trial randomised 3127 patients with a recent acute stroke to 6 months of fluoxetine or placebo and was published in the Lancet on 5 December 2018. The trial team decided to inform the participants of the results at exactly the same time as the Lancet publication, and also whether they had been allocated fluoxetine or placebo. In this report, we describe how we informed participants of the results.DesignIn the 6-month and 12-month follow-up questionnaires, we invited participants to provide an email address if they wished to be informed of the results of the trial. We re-opened our trial telephone helpline between 5 December 2018 and 31 March 2019.SettingUK stroke services.Participants3127 participants were randomised. 2847 returned 6-month follow-up forms and 2703 returned 12-month follow-up forms; the remaining participants had died (380), withdrawn consent or did not respond.ResultsOf those returning follow-up questionnaires, a total of 1845 email addresses were provided and a further 50 people requested results to be sent by post. Results were sent to all email and postal addresses provided; 309 emails were returned unrecognised. Seventeen people replied, of whom three called the helpline and the rest responded by email.ConclusionIt is feasible to disseminate results of large trials to research participants, though only around 60% of those randomised wanted to receive the results. The system we developed was efficient and required very little resource, and could be replicated by trialists in the future.Trial registration numberISRCTN83290762; Post-results.

Background The prevalence of azole resistance in Aspergillus fumigatus is uncertain in Australia. Azole exposure may select for resistance. We investigated the frequency of azole resistance in a large number of clinical and environmental isolates. Methods A. fumigatus isolates [148 human, 21 animal and 185 environmental strains from air (n = 6) and azole-exposed (n = 64) or azole-naive (n = 115) environments] were screened for azole resistance using the VIPcheck™ system. MICs were determined using the Sensititre™ YeastOne YO10 assay. Sequencing of the Aspergillus cyp51A gene and promoter region was performed for azole-resistant isolates, and cyp51A homology protein modelling undertaken. Results Non-WT MICs/MICs at the epidemiological cut-off value of one or more azoles were observed for 3/148 (2%) human isolates but not amongst animal, or environmental, isolates. All three isolates grew on at least one azole-supplemented well based on VIPcheck™ screening. For isolates 9 and 32, the itraconazole and posaconazole MICs were 1 mg/L (voriconazole MICs 0.12 mg/L); isolate 129 had itraconazole, posaconazole and voriconazole MICs of >16, 1 and 8 mg/L, respectively. Soil isolates from azole-exposed and azole-naive environments had similar geometric mean MICs of itraconazole, posaconazole and voriconazole (P > 0.05). A G54R mutation was identified in the isolates exhibiting itraconazole and posaconazole resistance, and the TR34/L98H mutation in the pan-azole-resistant isolate. cyp51A modelling predicted that the G54R mutation would prevent binding of itraconazole and posaconazole to the haem complex. Conclusions Azole resistance is uncommon in Australian clinical and environmental A. fumigatus isolates; further surveillance is indicated.

Background. The presence of patent foramen ovale (PFO) has been linked to many illness, including cryptogenic stroke, transient ischemic attack, migraine, platypnea-orthodeoxia syndrome and decompression sickness in scuba divers. Transesophageal echocardiography is the gold standard technique for the visualization of atrial septal anatomy, but it is a secondary level exam, not always available, with additional associated costs and not completely free from procedural risks. Standard transthoracic echocardiography (TTE) has a too low sensitivity for PFO screening. Purpose. The aim of the study was to assess the role of TTE associated with agitated saline contrast injection (contrast-TTE) as a gatekeeper for the identification of PFO in a large cohort of patients undergoing selection for percutaneous closure. Methods. A total of 200 patients undergoing a diagnostic work-up for the identification of PFO was imaged by contrast-TTE at rest and after provocative maneuvers (PM: Valsalva in all cases). Contrast TTE was graded from 0 to 4 on the bases of bubbles counting (0: no bubbles; 1: 30 bubbles; 4: complete LV opacification). PFO closure was performed after a consensual clinical decision by the cardiologist and the neurologist taking into account comprehensive imaging, clinical evaluation and thrombophilia screening. PFO closure was always monitored by intracardiac echocardiography. Results. At baseline contrast TTE was positive (≥2) in 34 patients (17%) while contrast TTE with PM was positive in 94 cases (47%). 27 out of 200 patients (14%) had an interatrial septal aneurysms. PFO closure was performed in 34 cases (17%). All of these had severe right-to-left shunting (≥3) at contrast TTE and 9 cases had also an interatrial septal aneurysms. The procedure was aborted in only 1 patient due to a complex defect anatomy. Conclusion. Contrast TTE with PM may be not only considered an accurate tool for the detection of PFO but may be also inserted in the diagnostic work- up as a primary gatekeeper for percutaneous closure. Severe shunting at contrast TTE influences final decision making in a large cohort of cases undergoing screening for PFO closure.

This study aimed to determine the physiological and thermoregulatory responses of individuals exercising in the heat (US military red flag conditions, wet-bulb globe temperature 31.5-32.2ºC) while consuming varied volumes of ambient temperature water and ice slurry.Participants (N = 12) walked on a treadmill for 3 hours at approximately 40% peak aerobic capacity in a hot environment while consuming ambient temperature (35.5°C) water (W), ice slurry (0°C, two-thirds shaved ice and one-third water) at a ratio of 2 g·kg(-1) body mass every 10 minutes (FS), and reduced volume ice slurry as described at a rate of 1 g·kg(-1) body mass every 10 minutes (HS). Trials were completed at least 14 days apart, in a randomized, repeated measures design.Percent body weight loss was higher during the HS trial (1.8 ± 0.01%) compared with FS (0.5 ± 0.01%; P.001) and W (0.6 ± 0.01%; P.001). Mean rectal temperature at 3 hours was lower during FS (37.8 ± 0.7°C) compared with HS (38.1 ± 0.8°C) and W (38.2 ± 0.8°C) (P = .04 vs HS, and P = .005 vs W, main effect for trial). No differences were found in rectal temperature between HS and W. Heart rate was lower at the end of the third hour during FS (141 ± 10 beats/min) compared with HS (157 ± 19 beats/min) and W (154 ± 18 beats/min) (P = .001 and P = .007, respectively, time × trial interaction). There were no differences in heart rate between HS and W.The temperature of consumed fluids may be as important as the volume for the management of thermoregulation and other physiological responses for extended work in hot environments.

A variety of dietary choices are marketed to enhance glycogen recovery after physical activity. Past research informs recommendations regarding the timing, dose, and nutrient compositions to facilitate glycogen recovery. This study examined the effects of isoenergetic sport supplements (SS) vs. fast food (FF) on glycogen recovery and exercise performance. Eleven males completed two experimental trials in a randomized, counterbalanced order. Each trial included a 90-min glycogen depletion ride followed by a 4-hr recovery period. Absolute amounts of macronutrients (1.54 ± 0.27 g·kg-1 carbohydrate, 0.24 ± 0.04 g·kg fat-1, and 0.18 ± 0.03g·kg protein-1) as either SS or FF were provided at 0 and 2 hr. Muscle biopsies were collected from the vastus lateralis at 0 and 4 hr post exercise. Blood samples were analyzed at 0, 30, 60, 120, 150, 180, and 240 min post exercise for insulin and glucose, with blood lipids analyzed at 0 and 240 min. A 20k time-trial (TT) was completed following the final muscle biopsy. There were no differences in the blood glucose and insulin responses. Similarly, rates of glycogen recovery were not different across the diets (6.9 ± 1.7 and 7.9 ± 2.4 mmol·kg wet weight- 1·hr-1 for SS and FF, respectively). There was also no difference across the diets for TT performance (34.1 ± 1.8 and 34.3 ± 1.7 min for SS and FF, respectively. These data indicate that short-term food options to initiate glycogen resynthesis can include dietary options not typically marketed as sports nutrition products such as fast food menu items.

Altitude exposure and exercise elicit oxidative stress in blood; however, exercise recovery at 5000 m attenuates oxidative stress. The purpose was to determine the altitude threshold at which blood oxidative stress is blunted during exercise recovery. Twelve males 18-28 years performed four-cycle ergometry bouts (60 min, 70% VO2max, at 975 m). In a randomised counterbalanced crossover design, participants recovered 6 h at 0, 1667, 3333 and 5000 m in a normobaric hypoxia chamber (recovery altitudes were simulated by using a computerised system in an environmental chamber by lowering the partial pressure of oxygen to match that of the respective altitude). Oxygen saturation was monitored throughout exercise recovery. Blood samples obtained pre-, post-, 1 h post- and 5 h post-exercise were assayed for ferric-reducing antioxidant plasma, Trolox equivalent antioxidant capacity, uric acid, lipid hydroperoxides and protein carbonyls. Muscle biopsies obtained pre and 6 h were analysed by real-time polymerase chain reaction to quantify expression of hemeoxgenase 1, superoxide dismutase 2 and nuclear factor (euthyroid-derived 2)-like factor. Pulse oximetry data were similar during exercise, but decreased for the three highest recovery elevations (0 m = 0%, 1667 m = -3%; 3333 m = -7%; 5000 m = -17%). A time-dependent oxidative stress occurred following exercise for all variables, but the two highest recovery altitudes partially attenuated the lipid hydroperoxide response (0 m = +135%, 1667 m = +251%, 3333 m = +99%; 5000 m = +108%). Data may indicate an altitude threshold between 1667 and 3333 m, above which the oxidative stress response is blunted during exercise recovery.

The purpose of this study was to investigate the effects of pneumatic compression pants on postexercise glycogen resynthesis. Active male subjects (n = 10) completed 2 trials consisting of a 90-minute glycogen depleting ride, followed by 4 hours of recovery with either a pneumatic compression device (PCD) or passive recovery (PR) in a random counterbalanced order. A carbohydrate beverage (1.8 g·kg bodyweight) was provided at 0 and 2 hours after exercise. Muscle biopsies (vastus lateralis) were obtained immediately and 4 hours after exercise for glycogen analyses. Blood samples were collected throughout recovery to measure glucose and insulin. Eight fingerstick blood samples for lactate were collected in the last 20 minutes of the exercise period and during the initial portion of the recovery period. Heart rate was monitored throughout the trial. During the PCD trial, subjects recovered using a commercially available recovery device (NormaTec PCD) operational at 0-60 and 120-180 minutes into recovery period. The same PCD was worn during the PR trial but was not turned on to create pulsatile pressures. There was no difference in muscle glycogen resynthesis during the recovery period (6.9 ± 0.8 and 6.9 ± 0.5 mmol·kg wet wt·h for the PR and PCD trials, respectively). Blood glucose, insulin, and lactate concentrations changed with respect to time but were not different between trials (p > 0.05). The use of PCD did not alter the rate of muscle glycogen resynthesis, blood lactate, or blood glucose and insulin concentrations associated with a postexercise oral glucose load.

Background The ability to physically perform at high altitude may require unique strategies to acclimatize before exposure. The effect of acute hypoxic exposure on the metabolic response of the skeletal muscle may provide insight into the value of short-term preacclimatization strategies. Objective To determine the human skeletal muscle response to a single acute bout of exercise in a hypoxic environment on metabolic gene expression. Methods Eleven recreationally active male participants (24 ± 4 years, 173 ± 20 cm, 82 ± 12 kg, 15.2 ± 7.1% fat, 4.0 ± 0.6 L/min maximal oxygen consumption) completed two 1-hour cycling exercise trials at 60% of peak power followed by 4 hours of recovery in ambient environmental conditions (975 m) and at normobaric hypoxic conditions simulating 3000 m in a randomized counterbalanced order. Muscle biopsies were obtained from the vastus lateralis before exercise and 4 hours after exercise for real-time polymerase chain reaction analysis of select metabolic genes. Results Gene expression of hypoxia-inducible factor 1 alpha, cytochrome c oxidase subunit 4, peroxisome proliferator-activated receptor gamma coactivator 1 alpha, hexokinase, phosphofructokinase, mitochondrial fission 1, and mitofusin-2 increased with exercise ( P P > .05). Optic atrophy 1 did not increase with exercise or differ between environmental conditions ( P > .05). Conclusions The improvements in mitochondrial function reported with intermittent hypoxic training may not be explained by a single acute hypoxic exposure, and thus it appears that a longer period of preacclimatization than a single exposure may be required.

Hypoxia due to altitude diminishes performance and alters exercise oxidative stress responses. While oxidative stress and exercise are well studied, the independent impact of hypoxia on exercise recovery remains unknown. Accordingly, we investigated hypoxic recovery effects on post-exercise oxidative stress. Physically active males (n = 12) performed normoxic cycle ergometer exercise consisting of ten high:low intensity intervals, 20 min at moderate intensity, and 6 h recovery at 975 m (normoxic) or simulated 5,000 m (hypoxic chamber) in a randomized counter-balanced cross-over design. Oxygen saturation was monitored via finger pulse oximetry. Blood plasma obtained pre- (Pre), post- (Post), 2 h post- (2Hr), 4 h post- (4Hr), and 6 h (6Hr) post-exercise was assayed for Ferric Reducing Ability of Plasma (FRAP), Trolox Equivalent Antioxidant Capacity (TEAC), Lipid Hydroperoxides (LOOH), and Protein Carbonyls (PC). Biopsies from the vastus lateralis obtained Pre and 6Hr were analyzed by real-time PCR quantify expression of Heme oxygenase 1 (HMOX1), Superoxide Dismutase 2 (SOD2), and Nuclear factor (euthyroid-derived2)-like factor (NFE2L2). PCs were not altered between trials, but a time effect (13 % Post-2Hr increase, p = 0.044) indicated exercise-induced blood oxidative stress. Plasma LOOH revealed only a time effect (p = 0.041), including a 120 % Post-4Hr increase. TEAC values were elevated in normoxic recovery versus hypoxic recovery. FRAP values were higher 6Hr (p = 0.045) in normoxic versus hypoxic recovery. Exercise elevated gene expression of NFE2L2 (20 % increase, p = 0.001) and SOD2 (42 % increase, p = 0.003), but hypoxic recovery abolished this response. Data indicate that recovery in a hypoxic environment, independent of exercise, may alter exercise adaptations to oxidative stress and metabolism.

To evaluate the previously developed physiological strain index (PSI) model using heart rate and skin temperature to provide further insight into the detection and estimation of thermal and physiological heat strain indices. A secondary aim was to characterize individuals who excel in their performance in the heat.56 male participants completed 2 walking trials (3.5 miles per hour, 5% grade) in controlled environments of 43.3 °C and 15.5 °C (40% humidity). Core and skin temperature, along with heart rate and PSI, were continually monitored during exercise. Participants completed a physical fitness test.The logistic regression model exhibited 4 false positives and 1 false negative at the 40% decision boundary. The "Not at Risk" group (N = 33) had higher body weight (84 ± 13 vs. 77 ± 10 kg, respectively) compared to the "At Risk" (N = 23) group, p0.05. The "Not at Risk" group had a faster 3-mile run time compared to the "At Risk" group (21:53 ± 3:13 vs. 25:16 ± 2:37, respectively), p0.05. During the Heat Trial, the "At Risk" group had a higher rating of perceived exertion at 60 and 90 minutes compared to the "Not at Risk" group (13.5 ± 2.8 vs. 11.5 ± 1.8 and 14.8 ± 3.2 vs. 12.2 ± 2.0 for "At Risk" vs. "Not at Risk" at 60 and 90 minutes, respectively), p0.05.The previously developed model relating heart rate and skin temperature to PSI is highly accurate at assessing heat risk status. Participants classified as "At Risk" had lower physical performance scores and different body weights compared to the "Not at Risk" group and perceived themselves as working harder during exercise in the heat.

The purpose of this investigation was to determine the impact of post-exercise environmental cold exposure on muscle glycogen, PGC-1α, and downstream transcription factors.Eight males cycled for 1h and recovered in either 7 °C (cold) or 20 °C (room temp) environment for 4h. Muscle biopsies were obtained pre, post, and 4h post exercise for the analysis of muscle glycogen and mRNA. During recovery participants consumed 1.8 g kg⁻¹ of body weight of an oral dextrose solution immediately following the post biopsy and 2h into recovery. Blood samples were obtained post exercise and at 30, 60, 120, 150, 180, and 240 min post exercise for the analysis of serum glucose and insulin AUC.Oxygen uptake was lower during room temp than during cold recovery (0.40 ± 0.05 L x min⁻¹ vs. 0.80 ± 0.12 L x min⁻¹; p0.01). There was no effect of temperature on muscle glycogen recovery or glucose AUC. However, insulin AUC was greater during the room temp trial compared to the cold trial (5139 ± 1412 vs. 4318 ± 1272, respectively; p=0.025). PGC-1α gene expression was higher (p=0.029), but ERRα and NRF2 were lower (p=0.019 and p=0.046, respectively) after recovery in the cold. There were no differences in NRF1 (p=.173) or TFAM (p=0.694).This investigation shows no effect of a cold recovery environment on glycogen re-synthesis but does demonstrate reduced ERRα and NRF2 mRNA despite elevations in PGC-1α mRNA when recovery post-exercise takes place in a cold environment.

The purpose of this study was to assess the physiological adaptations in physically fit individuals to a period of intensified training. Ten trained males cycled outdoors ~170 km day(-1) on 19 out of 21 days. Expired gas was collected on days 1 and 21 during maximal graded exercise and used for the determination of gross efficiency and whole body substrate use. Muscle biopsies were obtained before and after exercise on days 2 and 22 for the determination of mtDNA/gDNA ratio, gene expression, metabolic enzyme activity and glycogen use. Muscle glycogen before and after exercise, fat oxidation, and gross efficiency increased, carbohydrate oxidation decreased (p < 0.05), and VO(2max) did not change over the 21 days of training. Citrate synthase (CS), β-hydroxyacyl CoA dehydrogenase (β-HAD) and cytochrome c oxidase (COX) enzyme activity did not change with training. CS and β-HAD mRNA did not change with acute exercise or training. COX (subunit IV) mRNA increased with acute exercise (p < 0.05) but did not change over the 21 days. PGC-1α mRNA increased with acute exercise, but did not increase to the same degree on day 22 as it did on day 2 (p < 0.05). UCP3 mRNA decreased with training (p < 0.05). Acute exercise caused an increase in mitofusin2 (MFN2) mRNA (p < 0.05) and a trend for an increase in mtDNA/gDNA ratio (p = 0.057). However, training did not affect MFN2 mRNA or mtDNA/gDNA ratio. In response to 3,211 km of cycling, changes in substrate use and gross efficiency appear to be more profound than mitochondrial adaptations in trained individuals.

The aim of the present investigation was to examine the response of 80 plasma inflammatory analytes during five days of exercise in a hot (38 °C, 40% relative humidity) environment. 15 male participants (25±4yrs, 54±6 ml kg −1 min −1 VO 2 max), with no heat exposure within the previous 3 weeks, were asked to cycle in a hot environment at 70% of their VO 2 max workload until their terminal temperature was obtained, for 5 consecutive days. Terminal temperature was determined as the core temperature at volitional exhaustion or a core temperature of 39.5 °C, whichever came first. Blood samples were collected pre- and post-exercise on day 1 and day 5. Pre-trial urine specific gravity and body weight was not different on day 1 and day 5. Exercise time and heart rate at terminal temperature did not change during the five days. Of the 52 plasma analytes that increased in concentration on day 1, only 30 demonstrated increased concentrations at terminal temperature on day 5. Resting concentrations of 18, both pro- (IL-12p40, IL-15) and anti-inflammatory (IL-1ra, IL-10, IL-13) analytes were elevated on day 5 compared to day 1. We conclude that individuals completing consecutive days of exercise in the heat, but not definitively attaining heat acclimation, have increased resting levels of many inflammatory analytes associated with heat illness, but also demonstrate a reduced inflammatory response to a subsequent bout of exercise in the heat.

Purpose:The purpose of this study was to determine the metabolic profile during the 2006 Ironman World Championship in Kailua-Kona, Hawaii.Methods:One recreational male triathlete completed the race in 10:40:16. Before the race, linear regression models were established from both laboratory and feld measures to estimate energy expenditure and substrate utilization. The subject was provided with an oral dose of 2H218O approximately 64 h before the race to calculate total energy expenditure (TEE) and water turnover with the doubly labeled water (DLW) technique. Body weight, blood sodium and hematocrit, and muscle glycogen (via muscle biopsy) were analyzed pre- and postrace.Results:The TEE from DLW and indirect calorimetry was similar: 37.3 MJ (8,926 kcal) and 37.8 MJ (9,029 kcal), respectively. Total body water turnover was 16.6 L, and body weight decreased 5.9 kg. Hematocrit increased from 46 to 51% PCV. Muscle glycogen decreased from 152 to 48 mmoL/kg wet weight pre- to postrace.Conclusion:These data demonstrate the unique physiological demands of the Ironman World Championship and should be considered by athletes and coaches to prepare sufficient nutritional and hydration plans.

The purpose of this study was to impose a period of quantifiable intensified training to determine if commonly used diagnostic markers of overtraining parallel changes in physical performance and thus overtraining status. Eight trained male cyclists (24 ± 1 years, 71 ± 3 kg, VO2peak = 4.5 ± 0.1·L·min⁻¹) performed 21 days (3,211 km) of intensified training in the field where volume and intensity were increased over normal training. Salivary IgA, testosterone, and cortisol, 1-hour time trial performance, heart rate response, and profile of mood states (POMS) were collected and analyzed throughout the 21-day training period. The POMS category vigor declined from day 1 to day 4 and remained lower throughout (p0.05). There were no other statistical changes in overtraining parameters. However, individuals who demonstrated 2 or more symptoms of overtraining at any point throughout the 21 days were considered symptomatic and had a lower (p0.05) VO2peak (4.2 ± 0.1·vs. 4.7 ± 0.1 L·min⁻¹) and lower (p0.05) average workload during the initial 1-hour time trial (253 ± 5 vs. 288 ± 14 W). Interestingly, the 1-hour time trial power in these individuals with symptoms of overtraining did not decline (p0.05). These data demonstrate that markers of overtraining do not parallel a decrease in performance and should be interpreted with caution.

The purpose of this study was to determine the effects of a recovery beverage immediately after exercise on rates of muscle glycogen resynthesis in response to road cycling when nutritional supplementation was supplied during exercise and a solid meal was served two hours after exercise. Eight trained male cyclists, (25+/-4 years, 69.3+/-5.2 kg, VO2 peak=4.5+/-0.4 L.min(-1)) performed two 62 km outdoor training rides in a double-blind, randomized cross-over experiment. Subjects received a food bar and a commercial sport drink during each ride. A recovery beverage (40 g CHO+20 g PRO) or a placebo (PL) was administered 30 min post-exercise. At 2 h post-exercise, a solid meal was provided for both trials. There was no difference between trials at any time point for glycogen (140+/-9, 56+/-8, and 70+/-8 mmol.kg(-1)wet wt.(-1).hr.(-1) for pre, post, and 4 h post, respectively). The addition of a supplemental recovery beverage ingested soon after exercise did not significantly increase the rate of muscle glycogen resynthesis after 4 h of recovery when nutritional supplementation is provided during exercise and a meal is consumed 2 h after exercise.

The purpose of this study was to determine the effect of adding fenugreek extract (FG) to post-exercise carbohydrate feeding on glycogen resynthesis and subsequent exercise performance in normoglycemic male endurance athletes. A muscle biopsy sample was obtained from the vastus lateralis from subjects prior to exercise for 5 h at 50% of peak cycling power (52.1 +/- 3.3% of VO(2) peak). A second muscle biopsy sample was obtained immediately after exercise. Immediately after and 2 h after the second biopsy subjects ingested either an oral dose of dextrose (GLU) (1.8 g x kg BW(-1)) or GLU with FG containing 1.99 +/- 0.20 mg x kg(-1) 4-hydroxyisoleucine (GLU + FG) in a randomized, cross-over, double blind design. At 4 h post-exercise a third biopsy was taken and subjects received a standardised meal along with FG or a placebo capsule. At 15 h post-exercise subjects underwent their final muscle biopsy before completing a simulated 40 km cycling time trial. There was no difference in muscle glycogen at any time between GLU and GLU + FG. Additionally, 40 km time trial performance was similar for average power output (221 +/- 28 vs. 213 +/- 16 watts) and for time to completion (69.7 +/- 3.7 vs. 70.5 +/- 2.2 min) for the GLU and GLU + FG, respectively. Despite earlier data to the contrary, the present results do not support an effect of fenugreek supplementation on glycogen resynthesis, even though this may have been the result of differences in experimental protocol.

The purpose of this study was to compare glucose and insulin responses during an oral glucose tolerance test (OGTT) in cold (C), neutral (N), and hot (H) environments.Eleven males completed three 4-hour climate-controlled OGTT trials (C, 7.2°C; N, 22°C; and H, 43°C). Participants remained semireclined for 60 minutes before ingesting a 1.8 g/kg glucose beverage. Skin and rectal core temperatures were continuously monitored. Blood was collected just before glucose ingestion (time 0) and at 15, 30, 60, 90, 120, and 180 minutes, and analyzed for serum glucose, insulin, hematocrit, and hemoglobin. Expired gases were collected upon entering the chamber (-60 minutes), before glucose ingestion (0 minutes), and at 60, 120, and 180 minutes to determine V(O2) and respiratory exchange ratio.Rectal core temperature was greater in the H condition compared with both C and N (P.001). Rectal core temperature was not different between C and N, whereas skin temperature was different across all trials (H greater than N greater than C). The V(O2) was greater in C than in both H and N during all time points. Carbohydrate oxidation was greater in C compared with H and N (P0.001). Glucose was higher during H compared with C and N (P ≤ 0.002). Glucose was elevated in C compared with N. Insulin was higher in H compared with C (P = 0.009). Area under the curve for serum glucose was greater in H compared with C and N (P ≤ 0.001); however, there was no significant difference in area under the curve for insulin.These data indicate that after an OGTT, glucose and insulin are elevated in a hot environment.

Hypoxic exercise is characterized by workloads decrements. Because exercise and high altitude independently elicit redox perturbations, the study purpose was to examine hypoxic and normoxic steady-state exercise on blood oxidative stress. Active males (n = 11) completed graded cycle ergometry in normoxic (975 m) and hypoxic (3,000 m) simulated environments before programing subsequent matched intensity or workload steady-state trials. In a randomized counterbalanced crossover design, participants completed three 60-min exercise bouts to investigate the effects of hypoxia and exercise intensity on blood oxidative stress. Exercise conditions were paired as such; 60% normoxic VO2peak performed in a normoxic environment (normoxic intensity-normoxic environment, NI-NE), 60% hypoxic VO2peak performed in a normoxic environment (HI-NE), and 60% hypoxic VO2peak performed in a hypoxic environment (HI-HE). Blood plasma samples drawn pre (Pre), 0 (Post), 2 (2HR) and 4 (4HR) hr post exercise were analyzed for oxidative stress biomarkers including ferric reducing ability of plasma (FRAP), trolox equivalent antioxidant capacity (TEAC), lipid hydroperoxides (LOOH) and protein carbonyls (PCs). Repeated-measures ANOVA were performed, a priori significance of p ≤ .05. Oxygen saturation during the HI-HE trial was lower than NI-NE and HI-NE (p < .05). A Time × Trial interaction was present for LOOH (p = .013). In the HI-HE trial, LOOH were elevated for all time points post while PC (time; p = .001) decreased post exercise. As evidenced by the decrease in absolute workload during hypoxic VO2peak and LOOH increased during HI-HE versus normoxic exercise of equal absolute (HI-NE) and relative (NI-NE) intensities. Results suggest acute hypoxia elicits work decrements associated with post exercise oxidative stress.

Background Heat stress down-regulates mitochondrial function, while carbohydrate supplementation attenuates the exercise induced stimulation of mitochondrial biogenesis in humans. The effects of exogenous carbohydrate during exercise in the heat on metabolic mRNA have not been investigated in humans. The purpose of this study was to determine the impact of exercise with and without carbohydrate supplementation on skeletal muscle metabolic response in the heat. Methods Eight recreationally active males (4.05 ± 0.2 L.min-1) completed 2 trials which included 1 hr of cycling at 70% workload max and 3 hr recovery in a hot environment. Both trials were conducted in a climate controlled environmental chamber (38°C and 40% RH). The trials differed by the consumption of either a 6% carbohydrate (CHO) containing beverage (8 ml.kg-1.hr-1) or placebo (P) during exercise in random order. Muscle biopsies were obtained from the vastus lateralis before exercise, immediately post-exercise and at the end of the 3 hr recovery period. Muscle was analyzed for muscle glycogen and mRNA related to metabolic and mitochondrial development (MFN2, PGC-1α, GLUT4, UCP3). Expired gases were measured to determine whole body substrate use during exercise. Results Carbohydrate oxidation and muscle glycogen utilization did not differ between trials, whereas fat oxidation was elevated during exercise in P. Exercise caused an increase in PGC-1α, and GLUT4 (P

Background Special Tactics Officer (STO) selection is conducted to select officers to enter the combat controller training pipeline. The aims were to determine physical activity patterns, estimate energy expenditure, and identify whether return and/or unsuccessful candidates demonstrated differences in cortisol responses compared to non-selected and/or first-time attendees. Methods Participants completed the STO selection, consisting of 5 days of physical and mental challenges. Participants were equipped with ActiCals®, and saliva samples were collected throughout the STO selection. Results Average activity counts were 684 ± 200 counts∙min−1, with no group differences. Estimated energy expenditure was 4,105 ± 451 kcal∙day−1. Cortisol was elevated following extended physical training but returned to baseline during rest. Return candidates had significantly lower cortisol responses compared to first-timers, 0.43 ± 0.06 μg∙dl−1 versus 0.76 ± 0.18 μg∙dl−1, respectively, p Conclusions An individual's salivary cortisol response to the stresses incurred during the STO selection has the potential to be incorporated into the entire picture of a candidate's performance and ability to handle stress.

The purpose of this study was to determine the impact of increased local muscle temperature independent of core temperature on glycogenesis during recovery from exercise when adequate carbohydrate provisions were supplied. Nine rec- reationally active males (age, 23 ± 4 years; height, 178 ± 6 cm; weight 79 ± 9 kg) cycled for 92 min and recovered for 4 h. During recovery the subject's legs were randomly assigned as the heated limb (heat pack application) and control limb (exposed to room air). Participants received 2 carbohydrate feedings (1.8 g·kg -1 of body weight) at 0 and 2 h of recovery. Core temperature, intramuscular temperature, and leg circumference were monitored throughout recovery. Skeletal muscle biopsies samples of the vastus lateralis were obtained at the beginning and end of the 4-h recovery period on both legs and analyzed for glycogen and lactate. Core temperature did not change from throughout recovery. Muscle temperature in the heated limb was higher by 15 min and remained elevated throughout recovery compared with the control limb (p < 0.05). Leg circumference was not different between limbs. Lactate increased from postexercise to 4 h postexercise regardless of trial (p < 0.05). Muscle glycogen concentration increased with recovery and carbohydrate feeding in both limbs (p < 0.05) but was 22% higher in the heated limb compared with the control limb (p < 0.05). This study demonstrates increased glyco- genesis when local muscle temperature is increased independent of core temperature.

Cuddy, JS, Slivka, DR, Hailes, WS, and Ruby, BC. Factors of trainability and predictability associated with military physical fitness test success. J Strength Cond Res 25(12): 3486-3494, 2011-The purpose of this study was to determine the trainability of college-aged men using varied training programs and to assess factors associated with successfully passing a Special Operations Forces (SOF) physical fitness test (PFT). One hundred thirty-five male subjects were stratified into 3 training groups (run focused, calisthenic focused, or combined run and calisthenic) and were trained 3 times·per week for 12 weeks. Body composition and accelerometer activity patterns were measured pretraining and posttraining. The PFT performance (pull-ups, sit-ups, push-ups, and 1.5-mile run time) was measured weekly throughout the study period. The subjects exhibited reduced body fat (18.4 ± 7.7 to 16.9 ± 7.3), increased fat-free mass (66.1 ± 8.2 to 67.4 ± 7.9), reduced fat mass (15.8 ± 9.2 to 14.6 ± 8.9) from pretraining to posttraining, respectively (p0.05). All groups improved in each component of PFT performance with training (p0.05). There was a significant 20 ± 35% increase in 6-day average daily activity for the run-focused training group from pretraining and posttraining. The key indicators of a candidate's potential to successfully reach SOF PFT standards (in 12 weeks) were determined to be as follows: enter the pipeline being able to run 2.4 km in ≤10:41 minutes, have a body fat percentage of ≤12.9%, and participate in a minimum of 30 min·d of vigorous physical activity. Training an individual's relative run or calisthenic deficiency did not prove to be a better training approach compared with a program that emphasizes training both running and calisthenic activities.

Context: Telemetric core-temperature monitoring is becoming more widely used as a noninvasive means of monitoring core temperature during athletic events. Objective: To determine the effects of sensor ingestion timing on serial measures of core temperature during continuous exercise. Design: Crossover study. Setting: Outdoor dirt track at an average ambient temperature of 4.4°C ± 4.1°C and relative humidity of 74.1% ± 11.0%. Patients or Other Participants: Seven healthy, active participants (3 men, 4 women; age = 27.0 ± 7.5 years, height = 172.9 ± 6.8 cm, body mass = 67.5 ± 6.1 kg, percentage body fat = 12.7% ± 6.9%, peak oxygen uptake [V˙o2peak] = 54.4 ± 6.9 mL•kg−1•min−1) completed the study. Intervention(s): Participants completed a 45-minute exercise trial at approximately 70% V˙o2peak. They consumed core-temperature sensors at 24 hours (P1) and 40 minutes (P2) before exercise. Main Outcome Measure(s): Core temperature was recorded continuously (1-minute intervals) using a wireless data logger worn by the participants. All data were analyzed using a 2-way repeated-measures analysis of variance (trial × time), Pearson product moment correlation, and Bland-Altman plot. Results: Fifteen comparisons were made between P1 and P2. The main effect of time indicated an increase in core temperature compared with the initial temperature. However, we did not find a main effect for trial or a trial × time interaction, indicating no differences in core temperature between the sensors (P1 = 38.3°C ± 0.2°C, P2 = 38.3°C ± 0.4°C). Conclusions: We found no differences in the temperature recordings between the 2 sensors. These results suggest that assumed sensor location (upper or lower gastrointestinal tract) does not appreciably alter the transmission of reliable and repeatable measures of core temperature during continuous running in the cold.

Intracranial Haemorrhage (ICH) is a feared side effect of antiplatelet and anticoagulant agents; it is of particular prominence with the advent of the novel antiplatelet and anticoagulant agents. Postmarket Reports of Bleeding with NOACs highlighted the fact that newly marketed products, by virtue of their novelty alone, may elicit adverse-event reports at high rates; reporting rates decreasing over time (the Weber effect). Hence established medications, such as Warfarin and Aspirin, would be far less likely to elicit adverse-event reports than would newer medications with similar risks. The hypothesis of this study was to examine the frequency of antiplatelet and anticoagulant associated ICH (AAICH) in a consecutive series of patients referred to a National Neurosurgical Centre. We also compared the number of referrals of AAICH to the National Neurosurgical Centre in Beaumont Hospital with the number of ICH reported to the Health Products Regulatory Authority (HPRA) as an adverse event of these medications. The National Neurosurgical Centre in Beaumont has an estimated referral population of 4 million. All consecutive referrals from July 2013 to January 2014 were reviewed. Data collected included baseline demographics, antiplatelet/anticoagulation usage and indication for same, and CT brain findings of the ICH. The HPRA were contacted and supplied their adverse event reports for the same period. There were 977 consecutive patients with an ICH referred in this period. Of these 328 (33.6%), with a mean age of 77 yrs, female 42.6%, were on an antiplatelet and/or an anticoagulant agent; ASA alone (n = 166, 50.6%), Warfarin alone (106, 32.3%), Clopidogrel alone (11, 3.3%), Rivaroxaban alone (4, 1.2%), Dabigatran alone (4, 1.2%), ASA/dipyridamole alone (3, 0.9%). Thirty one (9.4%) patients were on two agents, 19 on ASA and Clopidogrel, 7 on ASA and Warfarin, 2 on Clopidogrel and Warfarin, 2 on Rivaroxaban and ASA, and 1 patient on ASA and Prasugrel. Three patients were on 3 agents, 2 on ASA, Clopidogrel and Warfarin, one on ASA, Clopidogrel and Rivaroxaban. We excluded 22 patients who had an ICH following thrombolysis or recent heparin therapy. The HPRA received 4 reports of ICH associated with antiplatelets or anticoagulants; 2 associated with Warfarin, 1 with Rivaroxaban and 1 with Rivaroxaban and Warfarin. This study highlights ASA as the most frequently documented antiplatelet/anticoagulant agent in a real life consecutive series of patients referred to a Neurosurgical Unit with ICH. In discussing the role of anticoagulation with patients, particularly the elderly, the significant risk of bleeding with ASA needs to be considered. These results also highlight the lack of adverse reporting with new and old medications alike. It emphasises the importance of reporting to national authorities so their statistics can be a true reflection of the number of adverse events, especially when these outcomes can be catastrophic, like ICH.

Optimal reperfusion in STEMI is the key goal of the National ACS programme. Some of the aims of the programme are reperfusion time (RT) of Aim The aim of this study was to compare patients with a STEMI referred directly from the community, either by the Ambulance service or GP, with the referrals from outside hospitals ED and UHG ED relating to the goals listed above. Method We used the heart-code database in UHG to identify all Code STEMI patients in the West of Ireland in 2014. Results In 2014 there were 324 Code STEMI referrals to UHG (18.8% female, average age 63), 311 (95.9%) of the referrals underwent angiography. Of all the Code STEMI patients 262 (80.8%) had a confirmed diagnosis of STEMI, either clinically or angiographically. Of 262 STEMI patients 108 were diagnosed in the prehospital phase and referred directly to the PCI-centre at UHG. In 64 cases (59.2%) ambulances bypassed non-PCI centres. The mean DDT was 68 min (SD 32.4). 24% had a DDT >90 min. There were 112 STEMI patients transferred from outside hospitals, 52 of the patients received thrombolysis prior to transfer. Excluding the later, DDT was 170 min (SD 128.7), DDT >90 mins in 63.7% of cases. The difference in DDT between the groups is statistically significant (p 120 min in 40.6%. 48 (42.8%) of the patients transferred from an outside hospital had PPCI, RT was 179 min (SD 120), RT >120 min in 63.8%. The difference in RT is statistically significant (p = 0.009). The ED in UHG referred 38 STEMI patients. Mean door to ECG time was 32 min (SD 7.9), 62.1% were outside the recommended 10 min. 30 (78.9%) patients had PPCI, mean RT was 127.5 min (SD 100.1), 66% of cases were outside recommended door to reperfusion time. The difference in RT between the ED and community group was significant (p = 0.013). The difference in RT was not significant when compared to the group referred from outside hospitals (p = 0.80). Conclusion The findings above clearly demonstrate the ACS programme in the West of Ireland has been successful in achieving its goals in direct transfers from the community, of 80% PPCI in STEMI with a mean RT

Thrombolysis is an important reperfusion strategy where primary PCI cannot be offered to STEMI patients within recommended timelines. The National ACS programme recommends the transfer of thrombolysed STEMI patients as soon as possible to a primary PCI centre. In cases of failed thrombolysis the patient should undergo immediate angiography and rescue PCI (RPCI). If thrombolysis is successful a strategy of routine early angiography is recommended. Aim The aim of this study was to determine the number of thrombolysed patients in the West of Ireland that were appropriately deferred for routine early angiography compared to those that were brought for rescue PCI, as determined by TIMI flow at time of coronary angiography and LV function on echo. Methods Data on all Code STEMI patients admitted to UHG is collected prospectively. Using this database we identified all patients who were thrombolysed for STEMI in 2014. Results Of 324 code STEMI admissions to UHG 59 (25.4% female, average age 62, age range 30–95) had received thrombolysis in an outside hospital. 27 (45.7%) were brought immediately to the lab on arrival at UHG; 14 (51.8%) had TIMI 1 or 0 flow, 13 (48.2%) had TIMI 2–3 flow. The main indication for immediate angiography was ongoing pain and STEMI. 30 (53.3%) patients had routine angiography; 4 (13.3%) had TIMI 0 or 1 flow, 26 (86.7%) had TIMI 2 or 3 flow. 2 (3.3%) patients had no angiography, 1 (1.7%) patient was too unstable and did not survive to discharge. The total mortality in the thrombolysed group was 4. Of the group brought for RPCI 24 (89%) proceeded to PCI, no intervention required in 3 (11%) cases, 2 of these being a ‘false call’ (LBBB, pericarditis), 2 patients in this subgroup did not survive. 62% had impaired LV function on initial echo, 38% with severely impaired LV function (EF Conclusion In our cohort of thrombolyed patients from the West of Ireland we found that the appropriate patients are being identified as successfully thrombolysed and having routine early angiography in keeping with international guidelines. This is demonstrated by the statistically significant difference in TIMI flow and initial LV systolic function between the 2 groups, highlighting that the delayed group are correctly identified as having a smaller ischaemic burden.

The ingestion of carbohydrate (CHO) and caffeine (CAF) during exercise is a common nutritional strategy used during endurance exercise. Caffeine has been proposed to increase sustained exercise capacity by increasing fat oxidation and sparing muscle glycogen. However, the addition of carbohydrate to

Objective. —To determine whether an organized intervention including data feedback, training in continuous quality improvement techniques, and site visits to other medical centers could improve the hospital mortality rates associated with coronary artery bypass graft (CABG) surgery. Design. —Regional intervention study. Patient demographic and historical data, body surface area, cardiac catheterization results, priority of surgery, comorbidity, and status at hospital discharge were collected on CABG patients in Northern New England between July 1, 1987, and July 31, 1993. Setting. —This study included all 23 cardiothoracic surgeons practicing in Maine, New Hampshire, and Vermont during the study period. Patients. —Data were collected on 15 095 consecutive patients undergoing isolated CABG procedures in Maine, New Hampshire, and Vermont during the study period. Interventions. —A three-component intervention aimed at reducing CABG mortality was fielded in 1990 and 1991. The interventions included feedback of outcome data, training in continuous quality improvement techniques, and site visits to other medical centers. Main Outcome Measure. —A comparison of the observed and expected hospital mortality rates during the postintervention period. Results. —During the postintervention period, we observed the outcomes for 6488 consecutive cases of CABG surgery. There were 74 fewer deaths than would have been expected. This 24% reduction in the hospital mortality rate was statistically significant ( P =.001). This reduction in mortality rate was relatively consistent across patient subgroups and was temporally associated with the interventions. Conclusion. —We conclude that a multi-institutional, regional model for the continuous improvement of surgical care is feasible and effective. This model may have applications in other settings. ( JAMA . 1996;275:841-846)