Urinary thymidine dimer excretion reflects personal ultraviolet radiation exposure levels.

Exposure to ultraviolet radiation (UVR) leads to skin DNA damage, specifically in the form of cyclobutane pyrimidine dimers, with thymidine dimers being the most common. Quantifying these dimers can indicate the extent of DNA damage resulting from UVR exposure. Here, a new liquid chromatography-mass spectrometry (LC-MS) method was used to quantify thymidine dimers in the urine after a temporary increase in real-life UVR exposure. Healthy Danish volunteers (n = 27) experienced increased UVR exposure during a winter vacation. Individual exposure, assessed via personally worn electronic UVR dosimeters, revealed a mean exposure level of 32.9 standard erythema doses (SEDs) during the last week of vacation. Morning urine thymidine dimer concentrations were markedly elevated both 1 and 2 days post-vacation, and individual thymidine dimer levels correlated with UVR exposure during the last week of the vacation. The strongest correlation with erythema-weighted personal UVR exposure (Power model, r2 = 0.64, p < 0.001) was observed when both morning urine samples were combined to measure 48-h thymidine dimer excretion, whereas 24-h excretion based on a single sample provided a weaker correlation (Power model, r2 = 0.55, p < 0.001). Sex, age, and skin phototype had no significant effect on these correlations. For the first time, urinary thymidine dimer excretion was quantified by LC-MS to evaluate the effect of a temporary increase in personal UVR exposure in a real-life setting. The high sensitivity to elevated UVR exposure and correlation between urinary excretion and measured SED suggest that this approach may be used to quantify DNA damage and repair and to evaluate photoprevention strategies.

Skeletal muscle phenotype and game performance in elite women football players.

We combined game activity analyses with skeletal muscle phenotypes and comprehensive physiological testing to elucidate factors of importance for physical performance in elite women's football. GPS-data from an experimental game, sprint and endurance testing, and muscle tissue analysis of metabolic enzyme activity, protein expression and fiber type composition were completed for international top-level women players (n = 20; age; 23 ± 4 yrs, height; 166 ± 10 cm, weight; 60 ± 8 kg; VO2max ; 51 ± 6 ml/min/kg). Muscle monocarboxylate transporter 4 (MCT4) protein expression explained 46% of the variance in total game distance, while the ability to maintain high-intensity running (HIR) during the final 15 min of the game correlated to myosin heavy chain 1 (MHCI) and Na+ -K+ ATPase ß1, FXYD1 (phospholemman) and superoxide dismutase 2 (SOD2) protein expression (range: r = 0.51-0.71; all p < 0.05). Total HIR distance correlated with (MHCIIa) protein expression (r = 0.51; p < 0.05), while muscle Na+ /H+ exchanger 1 (NHE1) protein explained 36% of the variance in game sprint distance (p < 0.05). Total game accelerations (actions >4 m/s2 ) correlated with platelet endothelial cell adhesion molecule (PECAM-1) protein expression (r = 0.51; p < 0.05), while concentric knee flexor strength explained 42-62% of the variance in intense decelerations (>4 m/s2 ). In conclusion, for elite women players' game endurance performance and resistance to end-game fatigue were affected by monocarboxylate transporter expression and myosin heavy chain profile. HIR was also correlated to ion transporter expression and muscle antioxidative capacity. Finally, the importance of functional strength and measures of muscle vascularization in relation to total game decelerations and accelerations, respectively, illustrates the complex physiological demands in elite women's football.

Quantifying the impact of heat on human physical work capacity; part III: the impact of solar radiation varies with air temperature, humidity, and clothing coverage.

Heat stress decreases human physical work capacity (PWC), but the extent to which solar radiation (SOLAR) compounds this response is not well understood. This study empirically quantified how SOLAR impacts PWC in the heat, considering wide, but controlled, variations in air temperature, humidity, and clothing coverage. We also provide correction equations so PWC can be quantified outdoors using heat stress indices that do not ordinarily account for SOLAR (including the Heat Stress Index, Humidex, and Wet-Bulb Temperature). Fourteen young adult males (7 donning a work coverall, 7 with shorts and trainers) walked for 1 h at a fixed heart rate of 130 beats∙min-1, in seven combinations of air temperature (25 to 45°C) and relative humidity (20 or 80%), with and without SOLAR (800 W/m2 from solar lamps). Cumulative energy expenditure in the heat, relative to the work achieved in a cool reference condition, was used to determine PWC%. Skin temperature was the primary determinant of PWC in the heat. In dry climates with exposed skin (0.3 Clo), SOLAR caused PWC to decrease exponentially with rising air temperature, whereas work coveralls (0.9 Clo) negated this effect. In humid conditions, the SOLAR-induced reduction in PWC was consistent and linear across all levels of air temperature and clothing conditions. Wet-Bulb Globe Temperature and the Universal Thermal Climate Index represented SOLAR correctly and did not require a correction factor. For the Heat Stress Index, Humidex, and Wet-Bulb Temperature, correction factors are provided enabling forecasting of heat effects on work productivity.

The HEAT-SHIELD project - Perspectives from an inter-sectoral approach to occupational heat stress.

OBJECTIVES: To provide perspectives from the HEAT-SHIELD project (www.heat-shield.eu): a multi-national, inter-sectoral, and cross-disciplinary initiative, incorporating twenty European research institutions, as well as occupational health and industrial partners, on solutions to combat negative health and productivity effects caused by working on a warmer world. METHODS: In this invited review, we focus on the theoretical and methodological advancements developed to combat occupational heat stress during the last five years of operation. RESULTS: We outline how we created climate forecast models to incorporate humidity, wind and solar radiation to the traditional temperature-based climate projections, providing the basis for timely, policy-relevant, industry-specific and individualized information. Further, we summarise the industry-specific guidelines we developed regarding technical and biophysical cooling solutions considering effectiveness, cost, sustainability, and the practical implementation potential in outdoor and indoor settings, in addition to field-testing of selected solutions with time-motion analyses and biophysical evaluations. All recommendations were adjusted following feedback from workshops with employers, employees, safety officers, and adjacent stakeholders such as local or national health policy makers. The cross-scientific approach was also used for providing policy-relevant information based on socioeconomic analyses and identification of vulnerable regions considered to be more relevant for political actions than average continental recommendations and interventions. DISCUSSION: From the HEAT-SHIELD experiences developed within European settings, we discuss how this inter-sectoral approach may be adopted or translated into actionable knowledge across continents where workers and societies are affected by escalating environmental temperatures.

Direct exposure of the head to solar heat radiation impairs motor-cognitive performance.

Health and performance impairments provoked by thermal stress are societal challenges geographically spreading and intensifying with global warming. Yet, science may be underestimating the true impact, since no study has evaluated effects of sunlight exposure on human brain temperature and function. Accordingly, performance in cognitively dominated and combined motor-cognitive tasks and markers of rising brainstem temperature were evaluated during exposure to simulated sunlight (equal to ~1000 watt/m2). Acute exposure did not affect any performance measures, whereas prolonged exposure of the head and neck provoked an elevation of the core temperature by 1 °C and significant impairments of cognitively dominated and motor task performances. Importantly, impairments emerged at considerably lower hyperthermia levels compared to previous experiments and to the trials in the presents study without radiant heating of the head. These findings highlight the importance of including the effect of sunlight radiative heating of the head and neck in future scientific evaluations of environmental heat stress impacts and specific protection of the head to minimize detrimental effects.

Impact of adrenaline and metabolic stress on exercise-induced intracellular signaling and PGC-1α mRNA response in human skeletal muscle.

This study tested the hypothesis that elevated plasma adrenaline or metabolic stress enhances exercise-induced PGC-1α mRNA and intracellular signaling in human muscle. Trained (VO2-max: 53.8 ± 1.8 mL min(-1) kg(-1)) male subjects completed four different exercise protocols (work load of the legs was matched): C - cycling at 171 ± 6 W for 60 min (control); A - cycling at 171 ± 6 W for 60 min, with addition of intermittent arm exercise (98 ± 4 W). DS - cycling at 171 ± 6 W interspersed by 30 sec sprints (513 ± 19 W) every 10 min (distributed sprints); and CS - cycling at 171 ± 6 W for 40 min followed by 20 min of six 30 sec sprints (clustered sprints). Sprints were followed by 3:24 min:sec at 111 ± 4 W. A biopsy was obtained from m. vastus lateralis at rest and immediately, and 2 and 5 h after exercise. Muscle PGC-1α mRNA content was elevated (P < 0.05) three- to sixfold 2 h after exercise relative to rest in C, A, and DS, with no differences between protocols. AMPK and p38 phosphorylation was higher (P < 0.05) immediately after exercise than at rest in all protocols, and 1.3- to 2-fold higher (P < 0.05) in CS than in the other protocols. CREB phosphorylation was higher (P < 0.05) 2 and 5 h after exercise than at rest in all protocols, and higher (P < 0.05) in DS than CS 2 h after exercise. This suggests that neither plasma adrenaline nor muscle metabolic stress determines the magnitude of PGC-1α mRNA response in human muscle. Furthermore, higher exercise-induced changes in AMPK, p38, and CREB phosphorylation are not associated with differences in the PGC-1α mRNA response.

Muscle variables of importance for physiological performance in competitive football.

PURPOSE: To examine how match performance parameters in trained footballers relate to skeletal muscle parameters, sprint ability and intermittent exercise performance. METHODS: 19 male elite football players completed an experimental game with physical performance determined by video analysis and exercise capacity assessed by intermittent Yo-Yo IR1 and IR2 tests, and a repeated sprint test (RST). Muscle tissue was obtained for analysis of metabolic enzyme maximal activity and key muscle protein expression. RESULTS: Total game distance, distance deficit from first to second half and high-intensity running in the final 15 min of the game were all correlated to the players' Yo-Yo IR1 performance (r = 0.55-0.87) and beta-hydroxyacyl-CoA-dehydrogenase (HAD) maximal activity (r = 0.55-0.65). Furthermore, platelet/endothelial cell adhesion molecule-1 (PECAM1) protein expression was weakly (r = 0.46) correlated to total game distance. Peak 5-min game distance faster than 21 km h(-1) was related to the Na(+)-K(+) ATPase subunit (α1, α2, ß1 and FXYD1) protein levels (r = 0.54-0.70), while Yo-Yo IR2 performance explained 40 % of the variance in high-intensity game distance. Total and 1-min peak sprint distance correlated to myosin heavy chain II/I ratio (MHCII/I ratio) and sarcoendoplasmic reticulum Ca(2+) ATPase isoform-1 (SERCA1) protein (r = 0.56-0.86), while phosphofructokinase (PFK) maximal activity also correlated to total sprint distance (r = 0.46). CONCLUSION: The findings emphasize the complexity of parameters predicting physical football performance with Yo-Yo IR1 and HAD as the best predictors of total distance, while high expression of Na(+)-K(+) ATPase proteins and the Yo-Yo IR2 test are better predictors of high-intensity performance. Finally, sprint performance relates to skeletal muscle fiber-type composition.

Thigh oxygen uptake at the onset of intense exercise is not affected by a reduction in oxygen delivery caused by hypoxia.

In response to hypoxic breathing most studies report slower pulmonary oxygen uptake (Vo2) kinetics at the onset of exercise, but it is not known if this relates to an actual slowing of the Vo2 in the active muscles(.) The aim of the present study was to evaluate whether thigh Vo2 is slowed at the onset of intense exercise during acute exposure to hypoxia. Six healthy male subjects (25.8 ± 1.4 yr, 79.8 ± 4.0 kg, means ± SE) performed intense (100 ± 6 watts) two-legged knee-extensor exercise for 2 min in normoxia (NOR) and hypoxia [fractional inspired oxygen concentration (Fi(O2)) = 0.13; HYP]. Thigh Vo2 was measured by frequent arterial and venous blood sampling and blood flow measurements. In arterial blood, oxygen content was reduced (P < 0.05) from 191 ± 5 ml O2/l in NOR to 180 ± 5 ml O2/l in HYP, and oxygen pressure was reduced (P < 0.001) from 111 ± 4 mmHg in NOR to 63 ± 4 mmHg in HYP. Thigh blood flow was the same in NOR and HYP, and thigh oxygen delivery was consequently reduced (P < 0.05) in HYP, but femoral arterial-venous oxygen difference and thigh Vo(2) were similar in NOR and HYP. In addition, muscle lactate release was the same in NOR and HYP, and muscle lactate accumulation during the first 25 s of exercise determined from muscle biopsy sampling was also similar (0.35 ± 0.07 and 0.36 ± 0.07 mmol·kg dry wt(-1)·s(-1) in NOR and HYP). Thus the increase in thigh Vo2 was not attenuated at the onset of intense knee-extensor exercise despite a reduction in oxygen delivery and pressure.

Skeletal muscle glycogen content and particle size of distinct subcellular localizations in the recovery period after a high-level soccer match.

Whole muscle glycogen levels remain low for a prolonged period following a soccer match. The present study was conducted to investigate how this relates to glycogen content and particle size in distinct subcellular localizations. Seven high-level male soccer players had a vastus lateralis muscle biopsy collected immediately after and 24, 48, 72 and 120 h after a competitive soccer match. Transmission electron microscopy was used to estimate the subcellular distribution of glycogen and individual particle size. During the first day of recovery, glycogen content increased by ~60% in all subcellular localizations, but during the subsequent second day of recovery glycogen content located within the myofibrils (Intramyofibrillar glycogen, a minor deposition constituting 10-15% of total glycogen) did not increase further compared with an increase in subsarcolemmal glycogen (-7 vs. +25%, respectively, P = 0.047). Conversely, from the second to the fifth day of recovery, glycogen content increased (53%) within the myofibrils compared to no change in subsarcolemmal or intermyofibrillar glycogen (P < 0.005). Independent of location, increment in particle size preceded increment in number of particles. Intriguingly, average particle size decreased; however, in the period from 3 to 5 days after the match. These findings suggest that glycogen storage in skeletal muscle is influenced by subcellular localization-specific mechanisms, which account for an increase in number of glycogen particles located within the myofibrils in the period from 2 to 5 days after the soccer match.

Maximal voluntary contraction force, SR function and glycogen resynthesis during the first 72 h after a high-level competitive soccer game.

The aim of this study was to examine maximal voluntary knee-extensor contraction force (MVC force), sarcoplasmic reticulum (SR) function and muscle glycogen levels in the days after a high-level soccer game when players ingested an optimised diet. Seven high-level male soccer players had a vastus lateralis muscle biopsy and a blood sample collected in a control situation and at 0, 24, 48 and 72 h after a competitive soccer game. MVC force, SR function, muscle glycogen, muscle soreness and plasma myoglobin were measured. MVC force sustained over 1 s was 11 and 10% lower (P < 0.05) after 0 and 24 h, respectively, compared with control. The rate of SR Ca(2+) uptake at 800 nM [Ca(2+)](free) was lower (P < 0.05) after 0 h (2.5 µmol Ca(2+) g prot(-1) min(-1)) than for all other time points (24 h: 5.1 µmol Ca(2+) g prot(-1) min(-1)). However, SR Ca(2+) release rate was not affected. Plasma myoglobin was sixfold higher (P < 0.05) immediately after the game, but normalised 24 h after the game. Quadriceps muscle soreness (0-10 VAS-scale) was higher (P < 0.05) after 0 h (3.6), 24 h (1.8), 48 h (1.1) and 72 h (1.4) compared with control (0.1). Muscle glycogen was 57 and 27% lower (P < 0.001) 0 and 24 h after the game compared with control (193 and 328 vs. 449 mmol kg d w(-1)). In conclusion, maximal voluntary contraction force and SR Ca(2+) uptake were impaired and muscle soreness was elevated after a high-level soccer game, with faster recovery of SR function in comparison with MVC force, soreness and muscle glycogen.

Effect of 2-wk intensified training and inactivity on muscle Na+-K+ pump expression, phospholemman (FXYD1) phosphorylation, and performance in soccer players.

The present study examined muscle adaptations and alterations in performance of highly trained soccer players with intensified training or training cessation. Eighteen elite soccer players were, for a 2-wk period, assigned to either a group that performed high-intensity training with a reduction in the amount of training (HI, n = 7), or an inactivity group without training (IN, n = 11). HI improved (P < 0.05) performance of the 4th, 6th, and 10th sprint in a repeated 20-m sprint test, and IN reduced (P < 0.05) performance in the 5th to the 10th sprints after the 2-wk intervention period. In addition, the Yo-Yo intermittent recovery level 2 test performance of IN was lowered from 845 +/- 48 to 654 +/- 30 m. In HI, the protein expression of the Na(+)-K(+) pump alpha(2)-isoform was 15% higher (P < 0.05) after the intervention period, whereas no changes were observed in alpha(1)- and beta(1)-isoform expression. In IN, Na(+)-K(+) pump expression was not changed. In HI, the FXYD1ser68-to-FXYD1 ratio was 27% higher (P < 0.01) after the intervention period, and, in IN, the AB_FXYD1ser68 signal was 18% lower (P < 0.05) after inactivity. The change in FXYD1ser68-to-FXYD1 ratio was correlated (r(2) = 0.35; P < 0.05) with change in performance in repeated sprint test. The present data suggest that short-term intensified training, even for trained soccer players, can increase muscle Na(+)-K(+) pump alpha(2)-isoform expression, and that cessation of training for 2 wk does not affect the expression of Na(+)-K(+) pump isoforms. Resting phosphorylation status of the Na(+)-K(+) pump is changed by training and inactivity and may play a role in performance during repeated, intense exercise.

Reduced volume and increased training intensity elevate muscle Na+-K+ pump alpha2-subunit expression as well as short- and long-term work capacity in humans.

The present study examined muscle adaptations and alterations in work capacity in endurance-trained runners as a result of a reduced amount of training combined with speed endurance training. For a 6- to 9-wk period, 17 runners were assigned to either a speed endurance group with a 25% reduction in the amount of training but including speed endurance training consisting of six to twelve 30-s sprint runs 3-4 times/wk (SET group n = 12) or a control group (n = 5), which continued the endurance training ( approximately 55 km/wk). For the SET group, the expression of the muscle Na(+)-K(+) pump alpha(2)-subunit was 68% higher (P < 0.05) and the plasma K(+) level was reduced (P < 0.05) during repeated intense running after 9 wk. Performance in a 30-s sprint test and the first of the supramaximal exhaustive runs was improved (P < 0.05) by 7% and 36%, respectively, after the speed endurance training period. In the SET group, maximal O(2) uptake was unaltered, but the 3-km (3,000-m) time was reduced (P < 0.05) from 10.4 +/- 0.1 to 10.1 +/- 0.1 min and the 10-km (10,000-m) time was improved from 37.3 +/- 0.4 to 36.3 +/- 0.4 min (means +/- SE). Muscle protein expression and performance remained unaltered in the control group. The present data suggest that both short- and long-term exercise performances can be improved with a reduction in training volume if speed endurance training is performed and that the Na(+)-K(+) pump plays a role in the control of K(+) homeostasis and in the development of fatigue during repeated high-intensity exercise.

Adipose triglyceride lipase in human skeletal muscle is upregulated by exercise training.

Mobilization of fatty acids from stored triacylglycerol (TG) in adipose tissue and skeletal muscle [intramyocellular triacylglycerol (IMTG)] requires activity of lipases. Although exercise training increases the lipolytic capacity of skeletal muscle, the expression of hormone-sensitive lipase (HSL) is not changed. Recently, adipose triglyceride lipase (ATGL) was identified as a TG-specific lipase in various rodent tissues. To investigate whether human skeletal muscle ATGL protein is regulated by endurance exercise training, 10 healthy young men completed 8 wk of supervised endurance exercise training. Western blotting analysis on lysates of skeletal muscle biopsy samples revealed that exercise training induced a twofold increase in skeletal muscle ATGL protein content. In contrast to ATGL, expression of comparative gene identification 58 (CGI-58), the activating protein of ATGL, and HSL protein was not significantly changed after the training period. The IMTG concentration was significantly decreased by 28% at termination of the training program compared with before. HSL-phoshorylation at Ser(660) was increased, HSL-Ser(659) phosporylation was unchanged, and HSL-phoshorylation at Ser(565) was decreased altogether, indicating an enhanced basal activity of this lipase. No change was found in the expression of diacylglycerol acyl transferase 1 (DGAT1) after training. Inhibition of HSL with a monospecific, small molecule inhibitor (76-0079) and stimulation of ATGL with CGI-58 revealed that significant ATGL activity is present in human skeletal muscle. These results suggest that ATGL in addition to HSL may be important for human skeletal muscle lipolysis.

Reduced volume but increased training intensity elevates muscle Na+-K+ pump alpha1-subunit and NHE1 expression as well as short-term work capacity in humans.

The present study examined muscle adaptations and alterations in work capacity in endurance-trained runners after a change from endurance to sprint training. Fifteen runners were assigned to either a sprint training (ST, n = 8) or a control (CON, n = 7) group. ST replaced their normal training by 30-s sprint runs three to four times a week, whereas CON continued the endurance training (approximately 45 km/wk). After the 4-wk sprint period, the expression of the muscle Na+-K+ pump alpha1-subunit and Na+/H+-exchanger isoform 1 was 29 and 30% higher (P < 0.05), respectively. Furthermore, plasma K+ concentration was reduced (P < 0.05) during repeated intense running. In ST, performance in a 30-s sprint test, Yo-Yo intermittent recovery test, and two supramaximal exhaustive runs was improved (P < 0.05) by 7, 19, 27, and 19%, respectively, after the sprint training period, whereas pulmonary maximum oxygen uptake and 10-k time were unchanged. No changes in CON were observed. The present data suggest a role of the Na+-K+ pump in the control of K+ homeostasis and in the development of fatigue during repeated high-intensity exercise. Furthermore, performance during intense exercise can be improved and endurance performance maintained even with a reduction in training volume if the intensity of training is very high.

Effect of two different intense training regimens on skeletal muscle ion transport proteins and fatigue development.

This study examined the effect of two different intense exercise training regimens on skeletal muscle ion transport systems, performance, and metabolic response to exercise. Thirteen subjects performed either sprint training [ST; 6-s sprints (n = 6)], or speed endurance training [SET; 30-s runs approximately 130% Vo(2 max), n = 7]. Training in the SET group provoked higher (P < 0.05) plasma K(+) levels and muscle lactate/H(+) accumulation. Only in the SET group was the amount of the Na(+)/H(+) exchanger isoform 1 (31%) and Na(+)-K(+)-ATPase isoform alpha(2) (68%) elevated (P < 0.05) after training. Both groups had higher (P < 0.05) levels of Na(+)-K(+)-ATPase beta(1)-isoform and monocarboxylate transporter 1 (MCT1), but no change in MCT4 and Na(+)-K(+)-ATPase alpha(1)-isoform. Both groups had greater (P < 0.05) accumulation of lactate during exhaustive exercise and higher (P < 0.05) rates of muscle lactate decrease after exercise. The ST group improved (P < 0.05) sprint performance, whereas the SET group elevated (P < 0.05) performance during exhaustive continuous treadmill running. Improvement in the Yo-Yo intermittent recovery test was larger (P < 0.05) in the SET than ST group (29% vs. 10%). Only the SET group had a decrease (P < 0.05) in fatigue index during a repeated sprint test. In conclusion, turnover of lactate/H(+) and K(+) in muscle during exercise does affect the adaptations of some but not all related muscle ion transport proteins with training. Adaptations with training do have an effect on the metabolic response to exercise and specific improvement in work capacity.

Interleukin-6 release from the human brain during prolonged exercise.

Interleukin (IL)-6 is a pleiotropic cytokine, which has a variety of physiological roles including functions within the central nervous system. Circulating IL-6 increases markedly during exercise, partly due to the release of IL-6 from the contracting skeletal muscles, and exercise-induced IL-6 may be linked with central fatigue, which is enhanced by hyperthermia. Exercise-induced IL-6 may also stimulate hepatic glycogenolysis, which is important during prolonged and repeated exercise. Thus, in a randomised order and separated by 60 min of rest, eight young male subjects completed two 60 min exercise bouts: one bout with a normal (38 degrees C) and the other with an elevated (39.5 degrees C) core temperature. The cerebral IL-6 response was determined on the basis of internal jugular venous to arterial IL-6 differences and global cerebral blood flow. There was no net release or uptake of IL-6 in the brain at rest or after 15 min of exercise, but a small release of IL-6 was observed after 60 min of exercise in the first bout (0.06 +/- 0.03 ng min(-1)). This release of IL-6 from the brain was five-fold greater at the end of the second bout (0.30 +/- 0.08 ng min(-1); P < 0.05) with no separate influence of hyperthermia. In conclusion, IL-6 is released from the brain during prolonged exercise in humans and it appears that the duration of the exercise rather than the increase in body temperature dictates the cerebral IL-6 response.