Auditing the Representation of Females Versus Males in Heat Adaptation Research.

The aim of this audit was to quantify female representation in research on heat adaptation. Using a standardized audit tool, the PubMed database was searched for heat adaptation literature from inception to February 2023. Studies were included if they investigated heat adaptation among female and male adults (≥18-50 years) who were free from noncommunicable diseases, with heat adaptation the primary or secondary outcome of interest. The number and sex of participants, athletic caliber, menstrual status, research theme, journal impact factor, Altmetric score, Field-Weighted Citation Impact, and type of heat exposure were extracted. A total of 477 studies were identified in this audit, including 7,707 participants with ∼13% of these being female. Most studies investigated male-only cohorts (∼74%, n = 5,672 males), with ∼5% (n = 360 females) including female-only cohorts. Of the 126 studies that included females, only 10% provided some evidence of appropriate methodological control to account for ovarian hormone status, with no study meeting best-practice recommendations. Of the included female participants, 40% were able to be classified to an athletic caliber, with 67% of these being allocated to Tier 2 (i.e., trained/developmental) or below. Exercise heat acclimation was the dominant method of heat exposure (437 interventions), with 21 studies investigating sex differences in exercise heat acclimation interventions. We recommend that future research on heat adaptation in female participants use methodological approaches that consider the potential impact of sexual dimorphism on study outcomes to provide evidence-based guidelines for female athletes preparing for exercise or competition in hot conditions.

Aspects of human uterine creatine metabolism during the menstrual cycle and at term pregnancy†.

Creatine metabolism likely contributes to energy homeostasis in the human uterus, but whether this organ synthesizes creatine and whether creatine metabolism is adjusted throughout the menstrual cycle and with pregnancy are largely unknown. This study determined endometrial protein expression of creatine-synthesizing enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), creatine kinase (CKBB), and the creatine transporter (SLC6A8) throughout the menstrual cycle in fertile and primary infertile women. It also characterized creatine metabolism at term pregnancy, measuring aspects of creatine metabolism in myometrial and decidual tissue. In endometrial samples, AGAT, GAMT, SLC6A8, and CKBB were expressed in glandular and luminal epithelial cells. Except for SLC6A8, the other proteins were also located in stromal cells. Irrespective of fertility, AGAT, GAMT, and SLC6A8 high-intensity immunohistochemical staining was greatest in the early secretory phase of the menstrual cycle. During the proliferative phase, staining for SLC6A8 protein was greater (P = 0.01) in the primary infertile compared with the fertile group. Both layers of the term pregnant uterus contained creatine, phosphocreatine, guanidinoacetic acid, arginine, glycine, and methionine; detectable gene and protein expression of AGAT, GAMT, CKBB, and ubiquitous mitochondrial CK (uMt-CK); and gene expression of SLC6A8. The proteins AGAT, GAMT, CKBB, and SLC6A8 were uniformly distributed in the myometrium and localized to the decidual glands. In conclusion, endometrial tissue has the capacity to produce creatine and its capacity is highest around the time of fertilization and implantation. Both layers of the term pregnant uterus also contained all the enzymatic machinery and substrates of creatine metabolism.

A Comparison of Sodium Citrate and Sodium Bicarbonate Ingestion: Blood Alkalosis and Gastrointestinal Symptoms.

This study compared the recommended dose of sodium citrate (SC, 500 mg/kg body mass) and sodium bicarbonate (SB, 300 mg/kg body mass) for blood alkalosis (blood [HCO3-]) and gastrointestinal symptoms (GIS; number and severity). Sixteen healthy individuals ingested the supplements in a randomized, crossover design. Gelatin capsules were ingested over 15 min alongside a carbohydrate-rich meal, after which participants remained seated for forearm venous blood sample collection and completion of GIS questionnaires every 30 min for 300 min. Time-course and session value (i.e., peak and time to peak) comparisons of SC and SB supplementation were performed using linear mixed models. Peak blood [HCO3-] was similar for SC (mean 34.2, 95% confidence intervals [33.4, 35.0] mmol/L) and SB (mean 33.6, 95% confidence intervals [32.8, 34.5] mmol/L, p = .308), as was delta blood [HCO3-] (SC = 7.9 mmol/L; SB = 7.3 mmol/L, p = .478). Blood [HCO3-] was ≥6 mmol/L above baseline from 180 to 240 min postingestion for SC, significantly later than for SB (120-180 min; p < .001). GIS were mostly minor, and peaked 80-90 min postingestion for SC, and 35-50 min postingestion for SB. There were no significant differences for the number or severity of GIS reported (p > .05 for all parameters). In summary, the recommended doses of SC and SB induce similar blood alkalosis and GIS, but with a different time course.

Oral digoxin effects on exercise performance, K+ regulation and skeletal muscle Na+ ,K+ -ATPase in healthy humans.

We investigated whether digoxin lowered muscle Na+ ,K+ -ATPase (NKA), impaired muscle performance and exacerbated exercise K+ disturbances. Ten healthy adults ingested digoxin (0.25 mg; DIG) or placebo (CON) for 14 days and performed quadriceps strength and fatiguability, finger flexion (FF, 105%peak-workrate , 3 × 1 min, fourth bout to fatigue) and leg cycling (LC, 10 min at 33% V O 2 peak ${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ and 67% V O 2 peak ${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ , 90% V O 2 peak ${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ to fatigue) trials using a double-blind, crossover, randomised, counter-balanced design. Arterial (a) and antecubital venous (v) blood was sampled (FF, LC) and muscle biopsied (LC, rest, 67% V O 2 peak ${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ , fatigue, 3 h after exercise). In DIG, in resting muscle, [3 H]-ouabain binding site content (OB-Fab ) was unchanged; however, bound-digoxin removal with Digibind revealed total ouabain binding (OB+Fab ) increased (8.2%, P = 0.047), indicating 7.6% NKA-digoxin occupancy. Quadriceps muscle strength declined in DIG (-4.3%, P = 0.010) but fatiguability was unchanged. During LC, in DIG (main effects), time to fatigue and [K+ ]a were unchanged, whilst [K+ ]v was lower (P = 0.042) and [K+ ]a-v greater (P = 0.004) than in CON; with exercise (main effects), muscle OB-Fab was increased at 67% V O 2 peak ${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ (per wet-weight, P = 0.005; per protein P = 0.001) and at fatigue (per protein, P = 0.003), whilst [K+ ]a , [K+ ]v and [K+ ]a-v were each increased at fatigue (P = 0.001). During FF, in DIG (main effects), time to fatigue, [K+ ]a , [K+ ]v and [K+ ]a-v were unchanged; with exercise (main effects), plasma [K+ ]a , [K+ ]v , [K+ ]a-v and muscle K+ efflux were all increased at fatigue (P = 0.001). Thus, muscle strength declined, but functional muscle NKA content was preserved during DIG, despite elevated plasma digoxin and muscle NKA-digoxin occupancy, with K+ disturbances and fatiguability unchanged. KEY POINTS: The Na+ ,K+ -ATPase (NKA) is vital in regulating skeletal muscle extracellular potassium concentration ([K+ ]), excitability and plasma [K+ ] and thereby also in modulating fatigue during intense contractions. NKA is inhibited by digoxin, which in cardiac patients lowers muscle functional NKA content ([3 H]-ouabain binding) and exacerbates K+ disturbances during exercise. In healthy adults, we found that digoxin at clinical levels surprisingly did not reduce functional muscle NKA content, whilst digoxin removal by Digibind antibody revealed an ∼8% increased muscle total NKA content. Accordingly, digoxin did not exacerbate arterial plasma [K+ ] disturbances or worsen fatigue during intense exercise, although quadriceps muscle strength was reduced. Thus, digoxin treatment in healthy participants elevated serum digoxin, but muscle functional NKA content was preserved, whilst K+ disturbances and fatigue with intense exercise were unchanged. This resilience to digoxin NKA inhibition is consistent with the importance of NKA in preserving K+ regulation and muscle function.

Factors Influencing Blood Alkalosis and Other Physiological Responses, Gastrointestinal Symptoms, and Exercise Performance Following Sodium Citrate Supplementation: A Review.

This review aimed to identify factors associated with (a) physiological responses, (b) gastrointestinal (GI) symptoms, and (c) exercise performance following sodium citrate supplementation. A literature search identified 33 articles. Observations of physiological responses and GI symptoms were categorized by dose (< 500, 500, and > 500 mg/kg body mass [BM]) and by timing of postingestion measurements (in minutes). Exercise performance following sodium citrate supplementation was compared with placebo using statistical significance, percentage change, and effect size. Performance observations were categorized by exercise duration (very short < 60 s, short ≥ 60 and ≤ 420 s, and longer > 420 s) and intensity (very high > 100% VO2max and high 90-100% VO2max). Ingestion of 500 mg/kg BM sodium citrate induced blood alkalosis more frequently than < 500 mg/kg BM, and with similar frequency to >500 mg/kg BM. The GI symptoms were minimized when a 500 mg/kg BM dose was ingested in capsules rather than in solution. Significant improvements in performance following sodium citrate supplementation were reported in all observations of short-duration and very high-intensity exercise with a 500 mg/kg BM dose. However, the efficacy of supplementation for short-duration, high-intensity exercise is less clear, given that only 25% of observations reported significant improvements in performance following sodium citrate supplementation. Based on the current literature, the authors recommend ingestion of 500 mg/kg BM sodium citrate in capsules to induce alkalosis and minimize GI symptoms. Supplementation was of most benefit to performance of short-duration exercise of very high intensity; further investigation is required to determine the importance of ingestion duration and timing.

Creatine metabolism in the uterus: potential implications for reproductive biology.

Creatine is an amino acid derivative synthesized from arginine, glycine and methionine. It serves as the substrate for the creatine kinase system, which is vital for maintaining ATP levels in tissues with high and fluctuating energy demand. There exists evidence that the creatine kinase system operates in both the endometrial and myometrial layers of the uterus. While use and regulation of this system in the uterus are not well understood, it is likely to be important given uterine tissues undergo phases of increased energy demand during certain stages of the female reproductive cycle, pregnancy, and parturition. This review discusses known adaptations of creatine metabolism in the uterus during the reproductive cycle (both estrous and menstrual), pregnancy and parturition, highlighting possible links to fertility and the existing knowledge gaps. Specifically, we discuss the adaptations and regulation of uterine creatine metabolite levels, cell creatine transport, de novo creatine synthesis, and creatine kinase expression in the various layers and cell types of the uterus. Finally, we discuss the effects of dietary creatine on uterine metabolism. In summary, there is growing evidence that creatine metabolism is up-regulated in uterine tissues during phases where energy demand is increased. While it remains unclear how important these adaptations are in the maintenance of healthy uterine function, furthering our understanding of uterine creatine metabolism may uncover strategies to combat poor embryo implantation and failure to conceive, as well as enhancing uterine contractile performance during labor.

Does maternal-fetal transfer of creatine occur in pregnant sheep?

Our aim was to determine the disposition of creatine in ovine pregnancy and whether creatine is transferred across the placenta from mother to fetus. Pregnant ewes received either 1) a continuous intravenous infusion of creatine monohydrate or saline from 122 to 131 days gestation, with maternal and fetal arterial blood and amniotic fluid samples collected daily for creatine analysis and fetal tissues collected at necropsy at 133 days for analysis of creatine content, or 2) a single systemic bolus injection of [13C]creatine monohydrate at 130 days of gestation, with maternal and fetal arterial blood, uterine vein blood, and amniotic fluid samples collected before and for 4 h after injection and analyzed for creatine, creatine isotopic enrichment, and guanidinoacetic acid (GAA; precursor of creatine) concentrations. Presence of the creatine transporter-1 (SLC6A8) and l-arginine:glycine amidinotransferase (AGAT; the enzyme synthesizing GAA) proteins were determined by Western blots of placental cotyledons. The 10-day creatine infusion increased maternal plasma creatine concentration three- to fourfold (P < 0.05) without significantly changing fetal arterial, amniotic fluid, fetal tissues, or placental creatine content. Maternal arterial 13C enrichment was increased (P < 0.05) after bolus [13C]creatine injection without change of fetal arterial 13C enrichment. SLC6A8 and AGAT proteins were identified in placental cotyledons, and GAA concentration was significantly higher in uterine vein than maternal artery plasma. Despite the presence of SLC6A8 protein in cotyledons, these results suggest that creatine is not transferred from mother to fetus in near-term sheep and that the ovine utero-placental unit releases GAA into the maternal circulation.

Short Duration Heat Acclimation in Australian Football Players.

This study examined if five sessions of short duration (27 min), high intensity, interval training (HIIT) in the heat over a nine day period would induce heat acclimation in Australian football (AF) players. Fourteen professional AF players were matched for VO2peak (mL·kg(-1)·min(-1)) and randomly allocated into either a heat acclimation (Acc) (n = 7) or Control (Con) group (n = 7). The Acc completed five cycle ergometer HIIT sessions within a nine day period on a cycle ergometer in the heat (38.7 ± 0.5 °C; 34.4 ± 1.3 % RH), whereas Con trained in thermo-neutral conditions (22.3 ± 0.2 °C; 35.8 ± 0. % RH). Four days prior and two days post HIIT participants undertook a 30 min constant load cycling test at 60% V̇O2peak in the heat (37.9 ± 0.1 °C; 28.5 ± 0.7 % RH) during which VO2, blood lactate concentration ([Lac(-)]), heart rate (HR), rating of perceived exertion (RPE), thermal comfort, core and skin temperatures were measured. Heat acclimation resulted in reduced RPE, thermal comfort and [Lac(-)] (all p < 0.05) during the submaximal exercise test in the heat. Heart rate was lower (p = 0.007) after HIIT, in both groups. Heat acclimation did not influence any other measured variables. In conclusion, five short duration HIIT sessions in hot dry conditions induced limited heat acclimation responses in AF players during the in-season competition phase. In practice, the heat acclimation protocol can be implemented in a professional team environment; however the physiological adaptations resulting from such a protocol were limited. Key pointsSome minor heat acclimation adaptations can be induced in professional AF players with five 27 min non-consecutive, short duration HIIT sessions in the heat.The heat acclimation protocol employed in this study was able to be implemented in a professional team sport environment during an actual competitive season.Elevating and maintaining a high core temperature sufficient for heat acclimation likely requires a longer heat training session or some pre-heating prior to exercise.

Fluid intake, hydration, work physiology of wildfire fighters working in the heat over consecutive days.

PURPOSE: (i) To evaluate firefighters' pre- and post-shift hydration status across two shifts of wildfire suppression work in hot weather conditions. (ii) To document firefighters' fluid intake during and between two shifts of wildfire suppression work. (iii) To compare firefighters' heart rate, activity, rating of perceived exertion (RPE), and core temperature across the two consecutive shifts of wildfire suppression work. METHOD: Across two consecutive days, 12 salaried firefighters' hydration status was measured immediately pre- and post-shift. Hydration status was also measured 2h post-shift. RPE was also measured immediately post-shift on each day. Work activity, heart rate, and core temperature were logged continuously during each shift. Ten firefighters also manually recorded their food and fluid intake before, during, and after both fireground shifts. RESULTS: Firefighters were not euhydrated at all measurement points on Day one (292±1 mOsm l(-1)) and euhydrated across these same time points on Day two (289±0.5 mOsm l(-1)). Fluid consumption following firefighters' shift on Day one (1792±1134ml) trended (P = 0.08) higher than Day two (1108±1142ml). Daily total fluid intake was not different (P = 0.27), averaging 6443±1941ml across both days. Core temperature and the time spent ≥ 70%HRmax were both elevated on Day one (when firefighters were not euhydrated). Firefighters' work activity profile was not different between both days of work. CONCLUSION: There was no difference in firefighters' pre- to post-shift hydration within each shift, suggesting ad libitum drinking was at least sufficient to maintain pre-shift hydration status, even in hot conditions. Firefighters' relative hypohydration on Day one (despite a slightly lower ambient temperature) may have been associated with elevations in core temperature, more time in the higher heart rate zones, and 'post-shift' RPE.

Effect of heat on firefighters' work performance and physiology.

Wildland firefighters often perform their duties under both hot and mild ambient temperatures. However, the direct impact of different ambient temperatures on firefighters' work performance has not been quantified. This study compared firefighters' work performance and physiology during simulated wildland firefighting work in hot (HOT; 32°C, 43% RH) and temperate (CON; 19°C, 56% RH) conditions. Firefighters (n=38), matched and allocated to either the CON (n=18) or HOT (n=20) condition, performed simulated self-paced wildland fire suppression tasks (e.g., hose rolling/dragging, raking) in firefighting clothing for six hours, separated by dedicated rest breaks. Task repetitions were counted (and converted to distance or area). Core temperature (Tc), skin temperature (Tsk), and heart rate were recorded continuously throughout the protocol. Urine output was measured before and during the protocol, and urine specific gravity (USG) analysed, to estimate hydration. Ad libitum fluid intake was also recorded. There were no differences in overall work output between conditions for any physical task. Heart rate was higher in the HOT (55±2% HRmax) compared to the CON condition (51±2% HRmax) for the rest periods between bouts, and for the static hose hold task (69±3% HRmax versus 65±3% HRmax). Tc and Tsk were 0.3±0.1°C and 3.1±0.2°C higher in the HOT compared to the CON trial. Both pre- and within- shift fluid intake were increased two-fold in the heat, and participants in the heat recorded lower USG results than their CON counterparts. There was no difference between the CON and HOT conditions in terms of their work performance, and firefighters in both experimental groups increased their work output over the course of the simulated shift. Though significantly hotter, participants in the heat also managed to avoid excessive cardiovascular and thermal strain, likely aided by the frequent rest breaks in the protocol, and through doubling their fluid intake. Therefore, it can be concluded that wildland firefighters are able to safely and efficiently perform their duties under hot conditions, at least over six hours.

Creatine supplementation during pregnancy: summary of experimental studies suggesting a treatment to improve fetal and neonatal morbidity and reduce mortality in high-risk human pregnancy.

While the use of creatine in human pregnancy is yet to be fully evaluated, its long-term use in healthy adults appears to be safe, and its well documented neuroprotective properties have recently been extended by demonstrations that creatine improves cognitive function in normal and elderly people, and motor skills in sleep-deprived subjects. Creatine has many actions likely to benefit the fetus and newborn, because pregnancy is a state of heightened metabolic activity, and the placenta is a key source of free radicals of oxygen and nitrogen. The multiple benefits of supplementary creatine arise from the fact that the creatine-phosphocreatine [PCr] system has physiologically important roles that include maintenance of intracellular ATP and acid-base balance, post-ischaemic recovery of protein synthesis, cerebral vasodilation, antioxidant actions, and stabilisation of lipid membranes. In the brain, creatine not only reduces lipid peroxidation and improves cerebral perfusion, its interaction with the benzodiazepine site of the GABAA receptor is likely to counteract the effects of glutamate excitotoxicity - actions that may protect the preterm and term fetal brain from the effects of birth hypoxia. In this review we discuss the development of creatine synthesis during fetal life, the transfer of creatine from mother to fetus, and propose that creatine supplementation during pregnancy may have benefits for the fetus and neonate whenever oxidative stress or feto-placental hypoxia arise, as in cases of fetal growth restriction, premature birth, or when parturition is delayed or complicated by oxygen deprivation of the newborn.

Heat Adaptation for Females: A Systematic Review and Meta-Analysis of Physiological Adaptations and Exercise Performance in the Heat.

BACKGROUND: Heat adaptation regimes are used to prepare athletes for exercise in hot conditions to limit a decrement in exercise performance. However, the heat adaptation literature mostly focuses on males, and consequently, current heat adaptation guidelines may not be optimal for females when accounting for the biological and phenotypical differences between sexes. OBJECTIVES: We aimed to examine: (1) the effects of heat adaptation on physiological adaptations in females; (2) the impact of heat adaptation on performance test outcomes in the heat; and (3) the impact of various moderators, including duration (minutes and/or days), total heat dose (°C.min), exercise intensity (kcal.min-1), total energy expended (kcal), frequency of heat exposures and training status on the physiological adaptations in the heat. METHODS: SPORTDiscus, MEDLINE Complete and Embase databases were searched to December 2022. Random-effects meta-analyses for resting and exercise core temperature, skin temperature, heart rate, sweat rate, plasma volume and performance tests in the heat were completed using Stata Statistical Software: Release 17. Sub-group meta-analyses were performed to explore the effect of duration, total heat dose, exercise intensity, total energy expended, frequency of heat exposure and training status on resting and exercise core temperature, skin temperature, heart rate and sweat rate. An explorative meta-regression was conducted to determine the effects of physiological adaptations on performance test outcomes in the heat following heat adaptation. RESULTS: Thirty studies were included in the systematic review; 22 studies were meta-analysed. After heat adaptation, a reduction in resting core temperature (effect size [ES] = - 0.45; 95% confidence interval [CI] - 0.69, - 0.22; p < 0.001), exercise core temperature (ES = - 0.81; 95% CI - 1.01, - 0.60; p < 0.001), skin temperature (ES = - 0.64; 95% CI - 0.79, - 0.48; p < 0.001), heart rate (ES = - 0.60; 95% CI - 0.74, - 0.45; p < 0.001) and an increase in sweat rate (ES = 0.53; 95% CI 0.21, 0.85; p = 0.001) were identified in females. There was no change in plasma volume (ES = - 0.03; 95% CI - 0.31, 0.25; p = 0.835), whilst performance test outcomes were improved following heat adaptation (ES = 1.00; 95% CI 0.56, 1.45; p < 0.001). Across all moderators, physiological adaptations were more consistently observed following durations of 451-900 min and/or 8-14 days, exercise intensity ≥ 3.5 kcal.min-1, total energy expended ≥ 3038 kcal, consecutive (daily) frequency and total heat dose ≥ 23,000 °C.min. The magnitude of change in performance test outcomes in the heat was associated with a reduction in heart rate following heat adaptation (standardised mean difference = - 10 beats.min-1; 95% CI - 19, - 1; p = 0.031). CONCLUSIONS: Heat adaptation regimes induce physiological adaptations beneficial to thermoregulation and performance test outcomes in the heat in females. Sport coaches and applied sport practitioners can utilise the framework developed in this review to design and implement heat adaptation strategies for females.

Does varying the ingestion period of sodium citrate influence blood alkalosis and gastrointestinal symptoms?

OBJECTIVES: To compare blood alkalosis, gastrointestinal symptoms and indicators of strong ion difference after ingestion of 500 mg.kg-1 BM sodium citrate over four different periods. METHODS: Sixteen healthy and active participants ingested 500 mg.kg-1 BM sodium citrate in gelatine capsules over a 15, 30, 45 or 60 min period using a randomized cross-over experimental design. Gastrointestinal symptoms questionnaires and venous blood samples were collected before ingestion, immediately post-ingestion, and every 30 min for 480 min post-ingestion. Blood samples were analysed for blood pH, [HCO3-], [Na+], [Cl-] and plasma [citrate]. Linear mixed models were used to estimate the effect of the ingestion protocols. RESULTS: For all treatments, blood [HCO3-] was significantly elevated above baseline for the entire 480 min post-ingestion period, and peak occurred 180 min post-ingestion. Blood [HCO3-] and pH were significantly elevated above baseline and not significantly below the peak between 150-270 min post-ingestion. Furthermore, blood pH and [HCO3-] were significantly lower for the 60 min ingestion period when compared to the other treatments. Gastrointestinal symptoms were minor for all treatments; the mean total session symptoms ratings (all times summed together) were between 9.8 and 11.6 from a maximum possible rating of 720. CONCLUSION: Based on the findings of this investigation, sodium citrate should be ingested over a period of less than 60 min (15, 30 or 45 min), and completed 150-270 min before exercise.

Risk of Adverse Outcomes in Females Taking Oral Creatine Monohydrate: A Systematic Review and Meta-Analysis.

Creatine Monohydrate (CrM) is a dietary supplement routinely used as an ergogenic aid for sport and training, and as a potential therapeutic aid to augment different disease processes. Despite its increased use in recent years, studies reporting potential adverse outcomes of CrM have been mostly derived from male or mixed sex populations. A systematic search was conducted, which included female participants on CrM, where adverse outcomes were reported, with meta-analysis performed where appropriate. Six hundred and fifty-six studies were identified where creatine supplementation was the primary intervention; fifty-eight were female only studies (9%). Twenty-nine studies monitored for adverse outcomes, with 951 participants. There were no deaths or serious adverse outcomes reported. There were no significant differences in total adverse events, (risk ratio (RR) 1.24 (95% CI 0.51, 2.98)), gastrointestinal events, (RR 1.09 (95% CI 0.53, 2.24)), or weight gain, (mean difference (MD) 1.24 kg pre-intervention, (95% CI -0.34, 2.82)) to 1.37 kg post-intervention (95% CI -0.50, 3.23)), in CrM supplemented females, when stratified by dosing regimen and subject to meta-analysis. No statistically significant difference was reported in measures of renal or hepatic function. In conclusion, mortality and serious adverse events are not associated with CrM supplementation in females. Nor does the use of creatine supplementation increase the risk of total adverse outcomes, weight gain or renal and hepatic complications in females. However, all future studies of creatine supplementation in females should consider surveillance and comprehensive reporting of adverse outcomes to better inform participants and health professionals involved in future trials.

Firefighter's Acute Inflammatory Response to Wildfire Suppression.

OBJECTIVES: The purpose of this study was to determine the inflammatory response to a 12-hour wildfire suppression shift, in firefighters attending the "Black Saturday" natural disaster. METHODS: Thirty-eight male volunteer firefighters provided venous blood samples before and after a 12-hour firefighting shift. Pre- to post-shift changes in pro-inflammatory (Interleukin [IL]-1ß, IL-2, IL-6, IL-8, IL-12P70, granulocyte macrophage-colony stimulating factor [GM-CSF], tumor necrosis factor-alpha [TNF-α], interferon-gamma [IFNγ]), and anti-inflammatory (IL-4, IL-5, IL-7, IL-10, IL-13) cytokines were measured with paired sample t tests, or Wilcoxon t tests for non-parametric data. RESULTS: Interleukin (IL)-6 (P = 0.003) and IL-8 (P = 0.017) were significantly increased following 12-hours of wildfire suppression. There was also a significant decrease in IL-10 (P = 0.021). CONCLUSIONS: The observed acute inflammatory response may have resulted from multiple stressors including physical exertion, thermal strain, or smoke inhalation experienced during the shift, and may be a necessary response for the body to adapt to stressor exposure.

Brief intense interval exercise activates AMPK and p38 MAPK signaling and increases the expression of PGC-1alpha in human skeletal muscle.

From a cell signaling perspective, short-duration intense muscular work is typically associated with resistance training and linked to pathways that stimulate growth. However, brief repeated sessions of sprint or high-intensity interval exercise induce rapid phenotypic changes that resemble traditional endurance training. We tested the hypothesis that an acute session of intense intermittent cycle exercise would activate signaling cascades linked to mitochondrial biogenesis in human skeletal muscle. Biopsies (vastus lateralis) were obtained from six young men who performed four 30-s "all out" exercise bouts interspersed with 4 min of rest (<80 kJ total work). Phosphorylation of AMP-activated protein kinase (AMPK; subunits alpha1 and alpha2) and the p38 mitogen-activated protein kinase (MAPK) was higher (P

Sodium citrate ingestion protocol impacts induced alkalosis, gastrointestinal symptoms, and palatability.

To compare the effect of 500 mg·kg-1 body mass (BM) sodium citrate ingested in solution or capsules on induced alkalosis, gastrointestinal symptoms and palatability. Twenty-four healthy and active participants completed two testing sessions, ingesting 500 mg·kg-1 BM sodium citrate within solution or capsules. Capillary blood samples were collected pre-ingestion, and every 30-min for 240-min post-ingestion; samples were analyzed for blood pH and [HCO3- ]. A validated questionnaire was used to quantify gastrointestinal symptoms at the same 30-min intervals. Palatability was quantified immediately after ingestion using a validated scale. There was a greater peak and change from baseline for capsules versus solution for blood pH (P < 0.001) and [HCO3- ] (P = 0.013). Blood pH and [HCO3- ] time to peak was 199 and 204 min, respectively, after capsule ingestion, both significantly later than after solution (P = 0.034, P = 0.001). Gastrointestinal symptoms were significantly elevated above baseline for both ingestion modes at each time point between 30 and 120 min after ingestion (P = 0.003), with no differences between modes at any time point (P = 0.644). Capsules were significantly more palatable than solution (P < 0.001). We recommend 500 mg·kg-1 BM sodium citrate ingestion in capsules, at least 200 min before exercise, to achieve greater alkalosis, minimize gastrointestinal symptoms, and maximize.

Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation.

Creatine monohydrate (CrM) supplementation has been shown to increase fat-free mass and muscle power output possibly via cell swelling. Little is known about the cellular response to CrM. We investigated the effect of short-term CrM supplementation on global and targeted mRNA expression and protein content in human skeletal muscle. In a randomized, placebo-controlled, crossover, double-blind design, 12 young, healthy, nonobese men were supplemented with either a placebo (PL) or CrM (loading phase, 20 g/day x 3 days; maintenance phase, 5 g/day x 7 days) for 10 days. Following a 28-day washout period, subjects were put on the alternate supplementation for 10 days. Muscle biopsies of the vastus lateralis were obtained and were assessed for mRNA expression (cDNA microarrays + real-time PCR) and protein content (Kinetworks KPKS 1.0 Protein Kinase screen). CrM supplementation significantly increased fat-free mass, total body water, and body weight of the participants (P < 0.05). Also, CrM supplementation significantly upregulated (1.3- to 5.0-fold) the mRNA content of genes and protein content of kinases involved in osmosensing and signal transduction, cytoskeleton remodeling, protein and glycogen synthesis regulation, satellite cell proliferation and differentiation, DNA replication and repair, RNA transcription control, and cell survival. We are the first to report this large-scale gene expression in the skeletal muscle with short-term CrM supplementation, a response that suggests changes in cellular osmolarity.

The influence of allopurinol on urinary purine loss after repeated sprint exercise in man.

The influence of allopurinol on urinary purine loss was examined in 7 active male subjects (age 24.9 +/- 3.0 years, weight 82.8 +/- 8.3 kg, V O2peak 48.1 +/- 6.9 mL.kg(-1).min(-1)). These subjects performed, in random order, a trial with 5 days of prior ingestion of a placebo or allopurinol. Each trial consisted of eight 10-second sprints on an air-braked cycle ergometer and was separated by at least a week. A rest period of 50 seconds separated each repeated sprint. Forearm venous plasma inosine, hypoxanthine (Hx) and uric acid concentrations were measured at rest and during 120 minutes of recovery from exercise. Urinary inosine, Hx, xanthine, and uric acid excretion were also measured before and for 24 hours after exercise. During the first 120 minutes of recovery, plasma Hx concentrations, as well as the urinary Hx and xanthine excretion rates, were higher (P < .05) with allopurinol compared with the placebo trial. In contrast, plasma uric acid concentration and urinary uric acid excretion rates were lower (P < .05) with allopurinol. The total urinary excretion of purines (inosine + Hx + xanthine + uric acid) above basal levels was higher in the allopurinol trial compared with placebo. These results indicate that the total urinary purine excretion after intermittent sprint exercise was enhanced with allopurinol treatment. Furthermore, the composition of urinary purines was markedly affected by this drug.