Passive heat therapy: a promising preventive measure for people at risk of adverse health outcomes during heat extremes.

The world is experiencing increased frequency, duration, and severity of life-threatening heat extremes. Most hospitalizations and excess deaths during extreme heat events are associated with preexisting diseases in older adults. As climate change persists, the global population ages and the number of individuals with chronic diseases expands, more people are at risk of adverse health outcomes during extreme heat events. Therefore, proactive preventive measures are urgently needed to mitigate heat-related health risks within these populations. In this context, passive heat therapy (e.g., hot baths, saunas, and water-perfused suits) emerges as a promising countermeasure to improve physiological resilience to a warming planet. Passive heating improves cardiovascular function and overall health in older adults and individuals living with chronic diseases, offering the prospect of reducing cardiovascular strain during hotter days. Moreover, some studies suggest that passive heat therapy can be an effective strategy for heat acclimation (i.e., improved thermoregulation). This review describes the existing literature on the effects of passive heat therapy on cardiovascular and thermoregulatory responses in individuals with higher heat-related health risks and explores the use of passive heating as a strategy for heat acclimation to mitigate health risks during extreme heat events.NEW & NOTEWORTHY Passive heat therapy improves cardiovascular function and health in middle-aged and older adults living with or without chronic diseases. In addition, preliminary studies indicate that passive heat interventions can induce heat acclimation, improving thermoregulatory responses. Thus, passive heat therapy could serve as a preventive measure for people at risk of adverse health outcomes during extreme heat events, improving resilience to ongoing climate change.

Why Humble Farmers May in Fact Grow Bigger Potatoes: A Call for Street-Smart Decision-Making in Sport.

BACKGROUND: The main task of applied sport science is to inform decision-making in sports practice, that is, enabling practitioners to compare the expectable outcomes of different options (e.g. training programs). MAIN BODY: The "evidence" provided may range from group averages to multivariable prediction models. By contrast, many decisions are still largely based on the subjective, experience-based judgement of athletes and coaches. While for the research scientist this may seem "unscientific" and even "irrational", it is important to realize the different perspectives: science values novelty, universal validity, methodological rigor, and contributions towards long-term advancement. Practitioners are judged by the performance outcomes of contemporary, specific athletes. This makes out-of-sample predictive accuracy and robustness decisive requirements for useful decision support. At this point, researchers must concede that under the framework conditions of sport (small samples, multifactorial outcomes etc.) near certainty is unattainable, even with cutting-edge methods that might theoretically enable near-perfect accuracy. Rather, the sport ecosystem favors simpler rules, learning by experience, human judgement, and integration across different sources of knowledge. In other words, the focus of practitioners on experience and human judgement, complemented-but not superseded-by scientific evidence is probably street-smart after all. A major downside of this human-driven approach is the lack of science-grade evaluation and transparency. However, methods are available to merge the assets of data- and human-driven strategies and mitigate biases. SHORT CONCLUSION: This work presents the challenges of learning, forecasting and decision-making in sport as well as specific opportunities for turning the prevailing "evidence vs. eminence" contrast into a synergy.

Does Higher Intensity Increase the Rate of Responders to Endurance Training When Total Energy Expenditure Remains Constant? A Randomized Controlled Trial.

BACKGROUND: Standardized training prescriptions often result in large variation in training response with a substantial number of individuals that show little or no response at all. The present study examined whether the response in markers of cardiorespiratory fitness (CRF) to moderate intensity endurance training can be elevated by an increase in training intensity. METHODS: Thirty-one healthy, untrained participants (46 ± 8 years, BMI 25.4 ± 3.3 kg m-2 and [Formula: see text]O2max 34 ± 4 mL min-1 kg-1) trained for 10 weeks with moderate intensity (3 day week-1 for 50 min per session at 55% HRreserve). Hereafter, the allocation into two groups was performed by stratified randomization for age, gender and VO2max response. CON (continuous moderate intensity) trained for another 16 weeks at moderate intensity, INC (increased intensity) trained energy-equivalent for 8 weeks at 70% HRreserve and then performed high-intensity interval training (4 × 4) for another 8 weeks. Responders were identified as participants with VO2max increase above the technical measurement error. RESULTS: There was a significant difference in [Formula: see text]O2max response between INC (3.4 ± 2.7 mL kg-1 min-1) and CON (0.4 ± 2.9 mL kg-1 min-1) after 26 weeks of training (P = 0.020). After 10 weeks of moderate training, in total 16 of 31 participants were classified as VO2max responders (52%). After another 16 weeks continuous moderate intensity training, no further increase of responders was observed in CON. In contrast, the energy equivalent training with increasing training intensity in INC significantly (P = 0.031) increased the number of responders to 13 of 15 (87%). The energy equivalent higher training intensities increased the rate of responders more effectively than continued moderate training intensities (P = 0.012). CONCLUSION: High-intensity interval training increases the rate of response in VO2max to endurance training even when the total energy expenditure is held constant. Maintaining moderate endurance training intensities might not be the best choice to optimize training gains. Trial Registration German Clinical Trials Register, DRKS00031445, Registered 08 March 2023-Retrospectively registered, https://www.drks.de/DRKS00031445.

Endotoxin Tolerance Acquisition and Altered Hepatic Fatty Acid Profile in Aged Mice.

(1) Background: Aging is linked to an altered immune response and metabolism. Inflammatory conditions, such as sepsis, COVID-19, and steatohepatitis are more prevalent in the elderly and steatosis is linked both to severe COVID-19 and sepsis. We hypothesized that aging is linked to a loss of endotoxin tolerance, which normally protects the host from excessive inflammation, and that this is accompanied by elevated levels of hepatic lipids. (2) Methods: An in vivo lipopolysaccharide (LPS) tolerance model in young and old mice was used and the cytokine serum levels were measured by ELISA. Cytokine and toll-like receptor gene expression was determined by qPCR in the lungs and the liver; hepatic fatty acid composition was assessed by GC-MS. (3) Results: The old mice showed a distinct potential for endotoxin tolerance as suggested by the serum cytokine levels and gene expression in the lung tissue. Endotoxin tolerance was less pronounced in the livers of the aged mice. However, the fatty acid composition strongly differed in the liver tissues of the young and old mice with a distinct change in the ratio of C18 to C16 fatty acids. (4) Conclusions: Endotoxin tolerance is maintained in advanced age, but changes in the metabolic tissue homeostasis may lead to an altered immune response in old individuals.

Forecasting football injuries by combining screening, monitoring and machine learning.

Identifying players or circumstances associated with an increased risk of injury is fundamental for successful risk management in football. So far, time-constant and volatile risk factors are generally considered separately in either a screening (constant) or a monitoring (volatile) approach each resulting in a restricted set of explanatory variables. Consequently, improvements in predictive accuracy may be expected when screening and monitoring data are combined, especially when analysed with current machine learning (ML) techniques.This trial was designed as a prospective observational cohort study aiming to forecast non-contact time-loss injuries in male professional football (soccer). Injuries were registered according to the Fuller consensus. Gradient boosting with ROSE upsampling within a leave-one-out cross-validation was used for data analysis. The hierarchical data structure was considered throughout. Different splits of the original dataset were used to probe the robustness of results.Data of 88 players from 4 teams and 51 injuries could be analysed. The cross-validated performance of the gradient boosted model (ROC area under the curve 0.61) was promising and higher compared to models without integration of screening data. Importantly, holdout test set performance was similar (ROC area under the curve 0.62) indicating prospect of generalizability to new cases. However, the variation of predictive accuracy and feature importance with different splits of the original dataset reflects the relatively low number of events.It is concluded that ML-based injury forecasting based on the integration of screening and monitoring data is promising. However, external prospective verification and continued model development are required.

Individualised reference ranges for markers of muscle recovery assessment in soccer.

Recently an individualisation algorithm has been developed and shown to significantly improve the diagnostic accuracy of creatine kinase (CK) and urea in endurance sports and Badminton. In this study, the applicability and benefit of this algorithm was evaluated using repeated measures data from 161 professional German soccer players monitored during the 2015-2017 seasons. Venous blood samples were collected after a day off (recovered state) and after a minimum of two strenuous training sessions within 48 h (non-recovered state) and analysed for CK and urea. Group-based reference ranges were derived from that same dataset to ensure the best possible reference for comparison. A z-test was conducted to analyse differences in error rates between individualised and group-based classifications. CK values for the individualised approach showed significantly lower error rates in the assessment of muscle recovery compared to both a population-based (p < .001; z-value: -17.01; test-pass error rate: 21 vs. 67%; test-fail: 19 vs. 64%) and a group-based cut-off (p < .001; z-value: -15.29; test-pass error rate: 65%; test-fail: 67%). It could be concluded that the assessment of muscle recovery in soccer using individualised interpretations of blood-borne markers may offer higher diagnostic accuracy than a population-based and a sample-specific group-based approach.HighlightsAssessing muscle recovery via CK using individualised ranges seems to offer a higher diagnostic accuracy than a sample-specific group-based analysis.Using an individualised algorithm seems to be a promising approach to overcome diagnostic problems arising from large inter- and intraindividual variability in blood parameters as it significantly improved the diagnostic accuracy of CK as a recovery marker.As recovery assessment in elite soccer ultimately aims at the accurate detection of differences in the individual player this algorithm seems to offer coaches and sport scientists a more sensitive approach compared to group-specific evaluations.

Dealing with small samples in football research.

In football research, 'small' trials with low statistical power are common. On the elite level, the inherently low number of participants obviously conflicts with the relevance of even tiny effects. However, general characteristics of football also contribute (e.g. multifactorially influenced and/or complex outcomes). Importantly, small sample sizes are problematic regardless of the study outcome with issues ranging from inconclusive results and low precision to unrepeatable 'discoveries' and overestimation of effect sizes. Therefore, meeting the calculated, target sample size is the first priority. If a suboptimal sample size must be accepted, a range of tools can improve insights. To begin with, some general aspects of data collection and analysis become more important and should be optimally implemented (e.g. reliability of measures). Building on this foundation, specific amendments are available on the levels of data collection (e.g. aggregated single-subject designs) and data analysis (e.g. Bayesian methods). The present commentary aims to give an overview of selected, practical tools for dealing with small sample sizes in football research and provide recommendations for their application in scenarios typical for the field. Importantly, versatility and adaptability are mirrored by the need for utmost transparency including a predetermined (ideally preregistered) study plan. Collaboration or counselling with an expert statistician is strongly encouraged.

Dwarfs on the Shoulders of Giants: Bayesian Analysis With Informative Priors in Elite Sports Research and Decision Making.

While sample sizes in elite sports are necessarily small, so are the effects that may be relevant. This conundrum is complicated by an understandable reluctance of athletes to comply with extensive study requirements. In Bayesian analyses, pre-existing knowledge (e.g., from sub-elite trials) can be formally included to supplement scarce data. Moreover, some design specifics for small sample research extend to the extreme case of a single subject. This provides the basis for actionable feedback (e.g., about individual responses) thereby incentivising participation. As a proof-of-concept, we conducted a replicated cross-over trial on the effect of cold-water immersion (CWI) on sprint performance recovery in soccer players. Times for 30 m linear sprint and the initial 5 m section, respectively, were measured by light gates before and 24 h after induction of fatigue. Data were analysed by Bayesian and by standard frequentist methods. Informative priors are based on a published metaanalysis. Seven players completed the trial. Sprint performance was 4.156 ± 0.193 s for 30 m linear sprint and 0.978 ± 0.064 s for the initial 5 m section. CWI improved recovery of sprint time for the initial 5 m section (difference to control: -0.060 ± 0.060 s, p = 0.004) but not for the full 30 m sprint (0.002 ± 0.115 s, p = 0.959), with general agreement between Bayesian and frequentist interval estimates. On the individual level, relevant differences between analytical approaches were present for most players. Changes in the two performance measures are correlated (p = 0.009) with a fairly good reproducibility of individual response patterns. Bayesian analyses with informative priors may be a practicable and meaningful option particularly for very small samples and when the analytical aim is decision making (use / don't use in the specific setting) rather than generalizable inference.

Poor Reliability of Measurement Instruments to Assess Acute Responses to Load in Soccer Players Irrespective of Biological Maturity Status.

PURPOSE: To assess the short-term reliability of measurement instruments to quantify the acute psychophysiological response to load in adolescent soccer players in relation to biological maturity. METHODS: Data were collected from 108 U12 to U17 soccer players on 2 consecutive weeks (pre, n = 32; at, n = 34; and post, n = 42 estimated peak height velocity). Measurements consisted of the Short Recovery and Stress Scale, a countermovement jump, assessment of leg stiffness, and a submaximal run to assess exercise heart rate and heart rate recovery. Test-retest reliability was assessed with the coefficient of variation (CV) and intraclass correlation coefficient (ICC). RESULTS: Items of the Short Recovery and Stress Scale showed poor reliability across maturity groups (CV = 7.0%-53.5%; ICC = .28 to .79). Only few countermovement jump variables (jump height, concentric impulse, and concentric velocity) possessed good reliability. For most variables of the countermovement jump, reliability was better for the post peak height velocity group followed by at-peak height velocity and prepeak height velocity. Very high levels of reliability across maturity groups were observed for exercise heart rate (CV < 1.8%; ICC > .94), while heart rate recovery was more variable (CV < 16.5%; ICC > .48). CONCLUSION: Results suggest that the majority of investigated variables have poor reliability, questioning their ability to detect small, yet meaningful changes in acute responses to load in adolescent soccer players.

Individual physiological and mitochondrial responses during 12 weeks of intensified exercise.

AIM: Observed effects of exercise are highly variable between individuals, and subject-by-training interaction (i.e., individual response variability) is often not estimated. Here, we measured mitochondrial (citrate synthetase, cytochrome-c oxidase, succinate dehydrogenase, and mitochondrial copy-number), performance markers (Wpeak , lactate threshold [LT], and VO2peak ), and fiber type proportions/expression (type I, type IIa, and type IIx) in multiple time points during 12-week of high-intensity interval training (HIIT) to investigate effects of exercise at the individual level. METHODS: Sixteen young (age: 33.1 ± 9.0 years), healthy men (VO2peak 35-60 ml/min/kg and BMI: 26.4 ± 4.2) from the Gene SMART study completed 12-week of progressive HIIT. Performance markers and muscle biopsies were collected every 4 weeks. We used mixed-models and bivariate growth models to quantify individual response and to estimate correlations between variables. RESULTS: All performance markers exhibited significant (Wpeak 0.56 ± 0.33 p = 0.003, LT 0.37 ± 0.35 p = 0.007, VO2peak 3.81 ± 6.13 p = 0.02) increases overtime, with subject-by-training interaction being present (95% CI: Wpeak 0.09-0.24, LT 0.06-0.18, VO2peak 0.27-2.32). All other measurements did not exhibit significant changes. Fiber type IIa proportions at baseline was significantly associated with all physiological variables (p < 0.05), and citrate synthetase and cytochrome-c oxidase levels at baseline and overtime (i.e., intercept and slope) presented significant covariance (p < 0.05). Finally, low correlations between performance and mitochondrial markers were observed. CONCLUSION: We identified a significant subject-by-training interaction for the performance markers. While for all other measures within-subject variability was too large and interindividual differences in training efficacy could not be verified. Changes in measurements in response to exercise were not correlated, and such disconnection should be further investigated by future studies.

Recovery-Stress Response of Blood-Based Biomarkers.

The purpose of this study was to investigate blood-based biomarkers and their regulation with regard to different recovery-stress states. A total of 35 male elite athletes (13 badminton, 22 soccer players) were recruited, and two venous blood samples were taken: one in a 'recovered' state (REC) after a minimum of one-day rest from exercise and another one in a 'non-recovered' state (NOR) after a habitual loading microcycle. Overall, 23 blood-based biomarkers of different physiologic domains, which address inflammation, muscle damage, and tissue repair, were analyzed by Luminex assays. Across all athletes, only creatine kinase (CK), interleukin (IL-) 6, and IL-17A showed higher concentrations at NOR compared to REC time points. In badminton players, higher levels of CK and IL-17A at NOR were found. In contrast, a higher value for S100 calcium-binding protein A8 (S100A8) at REC was found in badminton players. Similar differences were found for BDNF in soccer players. Soccer players also showed increased levels of CK, and IL-6 at NOR compared to REC state. Several molecular markers were shown to be responsive to differing recovery-stress states, but their suitability as biomarkers in training must be further validated.

Construct validity of age at predicted adult height and BAUS skeletal age to assess biological maturity in academy soccer.

BACKGROUND: The assessment of biological maturity status plays an important role in talent identification and development programs. AIM: To compare age at predicted adult height and BAUS skeletal age as indicators of biological maturity status in youth soccer players using a construct-validity approach. SUBJECTS AND METHODS: Participants were 114 players from the U12 to U17 age groups of a professional youth soccer academy. Maturity status was determined via percentage of predicted adult height based upon the Khamis-Roche method (somatic maturity) and assessed via the SonicBone BAUSTM system (skeletal maturity). Convergent and known-groups validity were evaluated between maturity assessment methods and by comparing maturity-related selection biases across age groups. RESULTS: Although maturity status indicators were largely interrelated (r = .94, 95%CL 0.91-0.96), concordance (κ = 0.31 to 0.39) and Spearman's rank-order correlations (ρ = 0.45-0.52) of classification methods were moderate. A selection bias towards early maturing players emerged in the U14 age group which remained relatively consistent through to the U17 age group. CONCLUSIONS: Results confirm the construct-validity of both methods to assess biological maturity status although further validation relative to established indicators of biological maturity is needed. Furthermore, caution is also warranted when interpreting maturity status classification methods interchangeably given the poor concordance between classification methods.

Improved Strength and Recovery After Velocity-Based Training: A Randomized Controlled Trial.

PURPOSE: The present intervention study examined the effects of intensity-matched velocity-based strength training with a 10% velocity loss (VL10) versus traditional 1-repetition maximum (1RM) based resistance training to failure (TRF) on 1RM and maximal oxygen uptake (V˙O2max) in a concurrent training setting. METHODS: Using the minimization method, 21 highly trained rowers (4 females and 17 males; 19.6 [2.1] y, 1.83 [0.07] m, 74.6 [8.8] kg, V˙O2max: 64.9 [8.5] mL·kg-1·min-1) were either assigned to VL10 or TRF. In addition to rowing endurance training (about 75 min·d-1), both groups performed strength training (5 exercises, 80% 1RM, 4 sets, 2-3 min interset recovery, 2 times/week) over 8 weeks. Squat, deadlift, bench row, and bench press 1RM and V˙O2max rowing-ergometer ramp tests were completed. Overall recovery and overall stress were monitored every evening using the Short Recovery and Stress Scale. RESULTS: Large and significant group × time interactions (P < .03, ηp2>.23, standard mean differences [SMD] > 0.65) in favor of VL10 (averaged +18.0% [11.3%]) were observed for squat, bench row, and bench press 1RM compared with TRF (averaged +8.0% [2.9%]). V˙O2max revealed no interaction effects (P = .55, ηp2=.01, standard mean difference < .23) but large time effects (P < .05, ηp2>.27). Significant group × time interactions (P = .001, ηp2>.54, SMD > |0.525|) in favor of VL10 were also observed for overall recovery and overall stress 24 and 48 hours after strength training. CONCLUSIONS: VL10 serves as a promising means to improve strength capacity at lower repetitions and stress levels in highly trained athletes. Future research should investigate the interference effects of VL10 in strength endurance sports and its effects when increasing weekly VL10 sessions within one macrocycle.

Menstrual cycle phase and elite female soccer match-play: influence on various physical performance outputs.

INTRODUCTION: The aim of the study was to investigate whether menstrual cycle phases influence the physical performance during soccer match-play. METHODS: Fifteen elite female soccer players, with physiologically normal menstrual cycles, competed in matches over a four-month period. Physical performance was assessed via GPS and expressed as meters per minute, and separated into four individualised thresholds (low, high, very high and sprinting). Seventy-six complete individual match observations, 36 from the follicular and 40 from the luteal phase were recorded. The differences in physical match performance parameters between the cycle phases were evaluated using a mixed linear model. RESULTS: The results of the current study indicate that very high-intensity running distance was significantly greater during the luteal phase compared to the follicular phase (5.90 ± 2.16 m.min-1 vs. 6.64 ± 2.72 m.min-1; p = 0.02). However, this finding was accompanied by large variations across matches (CV = 39.5%). CONCLUSIONS: Overall, the results suggest that the menstrual cycle phase does not influence match physical performance of female soccer players to a significant degree. Therefore, at present, interventions or other methods of coping with menstrual cycle phase do not seem necessary on a group/team level to maximise competitive physical performance.

Does Cold-Water Immersion After Strength Training Attenuate Training Adaptation?

PURPOSE: Cold-water immersion is increasingly used by athletes to support performance recovery. Recently, however, indications have emerged suggesting that the regular use of cold-water immersion might be detrimental to strength training adaptation. METHODS: In a randomized crossover design, 11 participants performed two 8-week training periods including 3 leg training sessions per week, separated by an 8-week "wash out" period. After each session, participants performed 10 minutes of either whole-body cold-water immersion (cooling) or passive sitting (control). Leg press 1-repetition maximum and countermovement jump performance were determined before (pre), after (post) and 3 weeks after (follow-up) both training periods. Before and after training periods, leg circumference and muscle thickness (vastus medialis) were measured. RESULTS: No significant effects were found for strength or jump performance. Comparing training adaptations (pre vs post), small and negligible negative effects of cooling were found for 1-repetition maximum (g = 0.42; 95% confidence interval [CI], -0.42 to 1.26) and countermovement jump (g = 0.02; 95% CI, -0.82 to 0.86). Comparing pre versus follow-up, moderate negative effects of cooling were found for 1-repetition maximum (g = 0.71; 95% CI, -0.30 to 1.72) and countermovement jump (g = 0.64; 95% CI, -0.36 to 1.64). A significant condition × time effect (P = .01, F = 10.00) and a large negative effect of cooling (g = 1.20; 95% CI, -0.65 to 1.20) were observed for muscle thickness. CONCLUSIONS: The present investigation suggests small negative effects of regular cooling on strength training adaptations.

Analysis of end-spurt behaviour in elite 800-m and 1500-m freestyle swimming.

To analyse the influence of distance, time point of competition, round and finishing position on end-spurt behaviour in swimming. Race results in 800-m and 1500-m freestyle swimming from the last 8 World Championships and 5 Olympic Games (1998-2016) including 1433 races and 528 swimmers were obtained. The end-spurt for each race was determined by means of an End-Spurt Indicator (ESI). The ESI was calculated by dividing the difference between the swim velocity of the last lap (SVLL) and the mean swim velocity of the middle part of the race (SVMP) by the respective individual standard deviation of SVMP. Subsequently, ESI was used as a dependent variable and influences were analysed using a linear mixed model with fixed effects for distance, time point of competition, round and finishing position. An end-spurt was evident in most swims for both race distances. The mean change in swim velocity between the middle part of the race and the last lap was 0.06 ± 0.02 m/s (1.2 ± 0.2 s) in the 800-m and 0.07 ± 0.02 m/s (1.5 ± 0.2 s) in the 1500-m. The finishing position within a race significantly affected the ESI (P < .001, t = 7.28). Specifically, when analysing finals only, ESI was significantly greater in medallists (5.76; quantile: 3.61 and 8.06) compared to non-medallists (4.06; quantile: 1.83 and 6.82; P = .001). The between-subject standard deviation was 1.66 (Cl: 1.42-1.97) with a relative variance component of 23%, while 77% of ESI variance remained unexplained. This is the first study using a newly developed indicator of end-spurt behaviour demonstrating that particularly medallists have a more pronounced end-spurt compared to non-medallists.

Monitoring training and recovery responses with heart rate measures during standardized warm-up in elite badminton players.

PURPOSE: To investigate short-term training and recovery-related effects on heart rate during a standardized submaximal running test. METHODS: Ten elite badminton players (7 females and 3 males) were monitored during a 12-week training period in preparation for the World Championships. Exercise heart rate (HRex) and perceived exertion were measured in response to a 5-min submaximal shuttle-run test during the morning session warm-up. This test was repeatedly performed on Mondays after 1-2 days of pronounced recovery ('recovered' state; reference condition) and on Fridays following 4 consecutive days of training ('strained' state). In addition, the serum concentration of creatine kinase and urea, perceived recovery-stress states, and jump performance were assessed before warm-up. RESULTS: Creatine kinase increased in the strained compared to the recovered state and the perceived recovery-stress ratings decreased and increased, respectively (range of average effects sizes: |d| = 0.93-2.90). The overall HRex was 173 bpm and the observed within-player variability (i.e., standard deviation as a coefficient of variation [CV]) was 1.3% (90% confidence interval: 1.2% to 1.5%). A linear reduction of -1.4% (-3.0% to 0.3%) was observed in HRex over the 12-week observational period. HRex was -1.5% lower (-2.2% to -0.9%) in the strained compared to the recovered state, and the standard deviation (as a CV) representing interindividual variability in this response was 0.7% (-0.6% to 1.2%). CONCLUSIONS: Our findings suggest that HRex measured during a standardized warm-up can be sensitive to short-term accumulation of training load, with HRex decreasing on average in response to consecutive days of training within repeated preparatory weekly microcycles. From a practical perspective, it seems advisable to determine intra-individual recovery-strain responses by repeated testing, as HRex responses may vary substantially between and within players.

Evaluating the Use of Circulating MicroRNA Profiles for Lung Cancer Detection in Symptomatic Patients.

Importance: The overall low survival rate of patients with lung cancer calls for improved detection tools to enable better treatment options and improved patient outcomes. Multivariable molecular signatures, such as blood-borne microRNA (miRNA) signatures, may have high rates of sensitivity and specificity but require additional studies with large cohorts and standardized measurements to confirm the generalizability of miRNA signatures. Objective: To investigate the use of blood-borne miRNAs as potential circulating markers for detecting lung cancer in an extended cohort of symptomatic patients and control participants. Design, Setting, and Participants: This multicenter, cohort study included patients from case-control and cohort studies (TREND and COSYCONET) with 3102 patients being enrolled by convenience sampling between March 3, 2009, and March 19, 2018. For the cohort study TREND, population sampling was performed. Clinical diagnoses were obtained for 3046 patients (606 patients with non-small cell and small cell lung cancer, 593 patients with nontumor lung diseases, 883 patients with diseases not affecting the lung, and 964 unaffected control participants). No samples were removed because of experimental issues. The collected data were analyzed between April 2018 and November 2019. Main Outcomes and Measures: Sensitivity and specificity of liquid biopsy using miRNA signatures for detection of lung cancer. Results: A total of 3102 patients with a mean (SD) age of 61.1 (16.2) years were enrolled. Data on the sex of the participants were available for 2856 participants; 1727 (60.5%) were men. Genome-wide miRNA profiles of blood samples from 3046 individuals were evaluated by machine-learning methods. Three classification scenarios were investigated by splitting the samples equally into training and validation sets. First, a 15-miRNA signature from the training set was used to distinguish patients diagnosed with lung cancer from all other individuals in the validation set with an accuracy of 91.4% (95% CI, 91.0%-91.9%), a sensitivity of 82.8% (95% CI, 81.5%-84.1%), and a specificity of 93.5% (95% CI, 93.2%-93.8%). Second, a 14-miRNA signature from the training set was used to distinguish patients with lung cancer from patients with nontumor lung diseases in the validation set with an accuracy of 92.5% (95% CI, 92.1%-92.9%), sensitivity of 96.4% (95% CI, 95.9%-96.9%), and specificity of 88.6% (95% CI, 88.1%-89.2%). Third, a 14-miRNA signature from the training set was used to distinguish patients with early-stage lung cancer from all individuals without lung cancer in the validation set with an accuracy of 95.9% (95% CI, 95.7%-96.2%), sensitivity of 76.3% (95% CI, 74.5%-78.0%), and specificity of 97.5% (95% CI, 97.2%-97.7%). Conclusions and Relevance: The findings of the study suggest that the identified patterns of miRNAs may be used as a component of a minimally invasive lung cancer test, complementing imaging, sputum cytology, and biopsy tests.

The glucocorticoid-induced leucine zipper mediates statin-induced muscle damage.

Statins, the most prescribed class of drugs for the treatment of hypercholesterolemia, can cause muscle-related adverse effects. It has been shown that the glucocorticoid-induced leucine zipper (GILZ) plays a key role in the anti-myogenic action of dexamethasone. In the present study, we aimed to evaluate the role of GILZ in statin-induced myopathy. Statins induced GILZ expression in C2C12 cells, primary murine myoblasts/myotubes, primary human myoblasts, and in vivo in zebrafish embryos and human quadriceps femoris muscle. Gilz induction was mediated by FOXO3 activation and binding to the Gilz promoter, and could be reversed by the addition of geranylgeranyl, but not farnesyl, pyrophosphate. Atorvastatin decreased Akt phosphorylation and increased cleaved caspase-3 levels in myoblasts. This effect was reversed in myoblasts from GILZ knockout mice. Similarly, myofibers isolated from knockout animals were more resistant toward statin-induced cell death than their wild-type counterparts. Statins also impaired myoblast differentiation, and this effect was accompanied by GILZ induction. The in vivo relevance of our findings was supported by the observation that gilz overexpression in zebrafish embryos led to impaired embryonic muscle development. Taken together, our data point toward GILZ as an essential mediator of the molecular mechanisms leading to statin-induced muscle damage.