Differential changes in appetite hormones post-prandially based on menstrual cycle phase and oral contraceptive use: A preliminary study.

This was a preliminary study that examined whether appetite regulation is altered during the menstrual cycle or with oral contraceptives. Ten naturally cycling females (NON-USERS) and nine tri-phasic oral contraceptive using females (USERS) completed experimental sessions during each menstrual phase (follicular phase: FP; ovulatory phase: OP; luteal phase: LP). Appetite perceptions and blood samples were obtained fasted, 30, 60, and 90 min post-prandial to measure acylated ghrelin, active glucagon-like peptide-1 (GLP-1), and total peptide tyrosine tyrosine (PYY). Changes were considered important if p < 0.100 and the effect size was ≥medium. There appeared to be a three-way (group x phase x time) interaction for acylated ghrelin where concentrations appeared to be greater in USERS versus NON-USERS during the OP 90-min post-prandial and during the LP fasted, and 90-min post-prandial. In USERS, ghrelin appeared to be greater 90-min post-prandial in the OP versus the FP with no other apparent differences between phases. There were no apparent differences between phases in NON-USERS. There appeared to be a three-way interaction for PYY where concentrations appeared to be greater in USERS during the FP 60-min post-prandial and during the OP 30-min post-prandial. In USERS PYY appeared to be greater 60-min post-prandial during the OP versus the LP with no other apparent differences. There were no apparent differences between phases in NON-USERS. There appeared to be no effect of group or phase on GLP-1, or appetite perceptions. These data demonstrate small effects of menstrual cycle phase and oral contraceptive use on the acylated ghrelin and total PYY response to a standardized meal, with no effects on active GLP-1 or perceived appetite, though more work with a large sample size is necessary.

Risk of bias in exercise science: A systematic review of 340 studies.

Risk of bias can contribute to irreproducible science and mislead decision making. Analyses of smaller subsections of the exercise science literature suggest many exercise science studies have unclear or high risk of bias. The current review (osf.io/jznv8) assesses whether this unclear or high risk of bias is more widespread in the exercise science literature and whether this bias has decreased since the publication of the 1996 Consolidated Standards of Reporting Trials (CONSORT) guidelines. We report significant reductions in selection, performance, detection, and reporting biases in 2020 compared with 1995 in the 340 of 5,451 studies assessed using the Cochrane Risk of Bias tool. Despite these improvements, most 2020 studies still had unclear or high risks of bias. These results underscore the need for methodological vigilance, adherence to reporting standards, and education on experimental bias. Factors contributing to these improvements, such advancements in education and journal requirements, remain uncertain.

Increasing aerobic exercise intensity fails to consistently improve the glycemic response in people living with prediabetes or type 2 diabetes mellitus: the INTENSITY trial.

Some individuals with prediabetes or type 2 diabetes mellitus (T2DM) who engage in exercise will not experience the anticipated improvements in glycemic control, referred to as non-responders. Increasing exercise intensity may improve the proportion of individuals who become responders. The objectives were to (i) identify responders and non-responders based on changes in glycated hemoglobin (HbA1c) in individuals with prediabetes or T2DM following 16 weeks of aerobic exercise; (ii) investigate if increasing exercise intensity enhances the responders' status for individuals not previously responding favourably to the intervention. Participants (n = 40; age = 58.0 years (52.0-66.0); HbA1c = 7.0% (6.0-7.2)) engaged in a two-phase, randomized study design. During phase one, participants performed 16 weeks of treadmill-based, supervised, aerobic exercise at 4.5 metabolic equivalents (METs) for 150 min per week. Thereafter, participants were categorized as responders, non-responders, or unclear based on the 90% confidence interval above, below, or crossing a 0.3% reduction in HbA1c. For phase two, participants were randomized to a maintained intensity (4.5 METs) or increased intensity (6.0 METs) group for 12 weeks. Following phase one, two (4.1%) participants were categorized as responders, four (8.2%) as non-responders, and 43 (87.7%) as unclear. Following phase two, two from the increased intensity group and one from the maintained intensity group experienced an improvement in response categorization. There were no significant between or within group (maintained vs. increased) differences in HbA1c. For most people with prediabetes or T2DM, increasing exercise intensity by 1.5 METs does not improve response categorization.

Including supramaximal verification reduced uncertainty in VO2peak response rate.

Many reports describe using a supramaximal verification phase-exercising at a power output higher than the highest power output recorded during an incremental cardiopulmonary test-to validate VO2max. The impact of verification phases on estimating the proportion of individuals who increased VO2peak in response to high-intensity interval training (HIIT) remains an underexplored area in the individual response literature. This analysis investigated the influence of same-day and separate-day verification phases during repeated measurements (incremental tests-INCR1 and INCR2; incremental tests + supramaximal verification phases-INCR1+ and INCR2+) of VO2peak on typical error (TE) and the proportion of individuals classified as responders (i.e., the response rate) following 4 weeks of HIIT (n = 25) or a no-exercise control period (n = 9). Incorporation of supramaximal verification consistently reduced the standard deviation of individual response, TE, and confidence interval (CI) widths. However, variances were statistically similar across all groups (p > 0.05). Response rates increased when incorporating either one (INCR1 to INCR1+; 24%-48%, p = 0.07) or two (INCR2 to INCR2+; 28%-48%, p = 0.063) supramaximal verification phases. However, response rates remained unchanged when either zero-based thresholds or smallest worthwhile difference response thresholds were used (50% and 90% CIs, all p > 0.05). Supramaximal verification phases reduced random variability in VO2peak response to HIIT. Compared with separate-day testing (INCR2 and INCR2+), the incorporation of a same-day verification (INCR1+) reduced CI widths the most. Researchers should consider using a same-day verification phase to reduce uncertainty and better estimate VO2peak response rate to HIIT.

AMPK and PGC-α following maximal and supramaximal exercise in men and women: a randomized cross-over study.

We tested the hypothesis that AMPK activation and peroxisome proliferator gamma coactivator 1 alpha (PGC-1α) expression are not augmented as exercise intensity (power output) increases from maximal to supramaximal intensities and conducted an exploratory analysis comparing AMPK activation and PGC-1α expression in males and females. Seventeen (n = 9 males; n = 8 females) recreationally active, healthy, young individuals volunteered to participate in the current study. Participants completed work matched interval exercise at 100% (Max) and 133% (Supra) of peak work rate (WRpeak). Intervals were 1 min in duration and participants were prescribed 6 and 8 intervals of Max and Supra, respectively, to equate external work across protocols. PGC-1α mRNA expression and activation of AMPK (p-ACC) were examined in muscle biopsy samples. Interval WR (watts; W), intensity (%WRpeak) and average HR (bpm), blood lactate (mmol/L) and rating of perceived exertion were all higher (all p < 0.05) in Supra. Fatigue was greater (p < 0.05) in Supra. PGC-1α mRNA expression significantly increased after exercise in Max (p < 0.01) and Supra (p < 0.01), but was not significantly different (p = 0.71) between intensities. A main effect of time (Pre - 0 h) (p < 0.01) was observed for p-ACC; however, no effect of intensity (p = 0.08) or interaction (p = 0.97) was observed. No significant effects of time (p = 0.05) intensity (p = 0.42), or interaction (p = 0.97) were observed for p-AMPK (Thr172). Exploratory sex analysis demonstrated a main effect of sex for p-ACC (greater p-ACC in males; p < 0.05) but not for p-AMPK or PGC-1α expression. Our results confirm that AMPK-PGC-1α signalling is not augmented following supramaximal exercise and provide novel data demonstrating a decrease in AMPK activation (p-ACC) in females compared to men. Trial registration: https://doi.org/10.17605/OSF.IO/U7PX9.

CARM1 drives mitophagy and autophagy flux during fasting-induced skeletal muscle atrophy.

CARM1 (coactivator associated arginine methyltransferase 1) has recently emerged as a powerful regulator of skeletal muscle biology. However, the molecular mechanisms by which the methyltransferase remodels muscle remain to be fully understood. In this study, carm1 skeletal muscle-specific knockout (mKO) mice exhibited lower muscle mass with dysregulated macroautophagic/autophagic and atrophic signaling, including depressed AMP-activated protein kinase (AMPK) site-specific phosphorylation of ULK1 (unc-51 like autophagy activating kinase 1; Ser555) and FOXO3 (forkhead box O3; Ser588), as well as MTOR (mechanistic target of rapamycin kinase)-induced inhibition of ULK1 (Ser757), along with AKT/protein kinase B site-specific suppression of FOXO1 (Ser256) and FOXO3 (Ser253). In addition to lower mitophagy and autophagy flux in skeletal muscle, carm1 mKO led to increased mitochondrial PRKN/parkin accumulation, which suggests that CARM1 is required for basal mitochondrial turnover and autophagic clearance. carm1 deletion also elicited PPARGC1A (PPARG coactivator 1 alpha) activity and a slower, more oxidative muscle phenotype. As such, these carm1 mKO-evoked adaptations disrupted mitophagy and autophagy induction during food deprivation and collectively served to mitigate fasting-induced muscle atrophy. Furthermore, at the threshold of muscle atrophy during food deprivation experiments in humans, skeletal muscle CARM1 activity decreased similarly to our observations in mice, and was accompanied by site-specific activation of ULK1 (Ser757), highlighting the translational impact of the methyltransferase in human skeletal muscle. Taken together, our results indicate that CARM1 governs mitophagic, autophagic, and atrophic processes fundamental to the maintenance and remodeling of muscle mass. Targeting the enzyme may provide new therapeutic approaches for mitigating skeletal muscle atrophy.

No acute hyperglycemia induced impairment in brachial artery flow-mediated dilation before or after aerobic exercise training in young recreationally active males.

There is some evidence that transient endothelial dysfunction induced by acute hyperglycemia may be attenuated by a single bout of aerobic exercise. However, the impact of aerobic exercise training on acute hyperglycemia-induced endothelial dysfunction has not been explored. The purpose of this study was to determine the impact of aerobic exercise training on the endothelial function response to acute hyperglycemia. Brachial artery flow-mediated dilation (FMD) was assessed in 24 healthy males (21 ± 1 years) pre-, 60 and 90 min post ingestion of 75 g of glucose. Participants completed a four-week control (CON; n = 13) or exercise training (EX; n = 11) intervention. The EX group completed four weeks of cycling exercise (30 min, 4×/week at 65% work rate peak). Cardiorespiratory fitness ([Formula: see text]O2peak) increased and resting HR decreased in EX, but not CON post-intervention (p < 0.001). Glucose and insulin increased (p < 0.001) following glucose ingestion, with no significant difference pre- and post-intervention. In contrast to previous research, FMD was unaffected by glucose-ingestion, pre- and post-intervention in both groups. In conclusion, acute hyperglycemia did not impair endothelial function, before or after exercise training. Relatively high baseline fitness ([Formula: see text]O2peak ~ 46 mL/kg/min) and young age may have contributed to the lack of impairment observed. Further research is needed to examine the impact of exercise training on hyperglycemia-induced impairments in endothelial function in sedentary males and females.

Impacts of altered exercise volume, intensity, and duration on the activation of AMPK and CaMKII and increases in PGC-1α mRNA.

The purpose of this review is to explore and discuss the impacts of augmented training volume, intensity, and duration on the phosphorylation/activation of key signaling protein - AMPK, CaMKII and PGC-1α - involved in the initiation of mitochondrial biogenesis. Specifically, we explore the impacts of augmented exercise protocols on AMP/ADP and Ca2+ signaling and changes in post exercise PGC - 1α gene expression. Although AMP/ADP concentrations appear to increase with increasing intensity and during extended durations of higher intensity exercise AMPK activation results are varied with some results supporting and intensity/duration effect and others not. Similarly, CaMKII activation and signaling results following exercise of different intensities and durations are inconsistent. The PGC-1α literature is equally inconsistent with only some studies demonstrating an effect of intensity on post exercise mRNA expression. We present a novel meta-analysis that suggests that the inconsistency in the PGC-1α literature may be due to sample size and statistical power limitations owing to the effect of intensity on PGC-1α expression being small. There is little data available regarding the impact of exercise duration on PGC-1α expression. We highlight the need for future well designed, adequately statistically powered, studies to clarify our understanding of the effects of volume, intensity, and duration on the induction of mitochondrial biogenesis by exercise.

Exploring interindividual differences in fasting and postprandial insulin sensitivity adaptations in response to sprint interval exercise training.

Previous studies have concluded that wide variance in changes in insulin sensitivity markers following exercise training demonstrates heterogeneity in individual trainability. However, these studies frequently don't account for technical, biological, and random within-subject measurement error. We used the standard deviation of individual responses (SDIR) to determine whether interindividual variability in trainability exists for fasting and postprandial insulin sensitivity outcomes following low-volume sprint interval training (SIT). We pooled data from 63 untrained participants who completed 6 weeks of SIT (n = 49; VO2max: 35 (7) mL⋅kg-1⋅min-1) or acted as no-intervention controls (n = 14; VO2max: 34 (6) mL⋅kg-1⋅min-1). Fasting and oral glucose tolerance test (OGTT)-derived measures of insulin sensitivity were measured pre- and post-intervention. SDIR values were positive and exceeded a small effect size threshold for changes in fasting glucose (SDIR = 0.27 [95%CI 0.07,0.38] mmol⋅L-1), 2-h OGTT glucose (SDIR = 0.89 [0.22,1.23] mmol⋅L-1), glucose area-under-the-curve (SDIR = 66.4 [-81.5,124.3] mmol⋅L-1⋅120min-1) and The Cederholm Index (SDIR = 7.2 [-16.0,19.0] mg⋅l2⋅mmol-1⋅mU-1⋅min-1), suggesting meaningful individual responses to SIT, whilst SDIR values were negative for fasting insulin, fasting insulin resistance and insulin AUC. For all variables, the 95% CIs were wide and/or crossed zero, highlighting uncertainty about the existence of true interindividual differences in exercise trainability. Only 2-22% of participants could be classified as responders or non-responders with more than 95% certainty. Our findings demonstrate it cannot be assumed that variation in changes in insulin sensitivity following SIT is attributable to inherent differences in trainability, and reiterate the importance of accounting for technical, biological, and random error when examining heterogeneity in health-related training adaptations.Highlights This study tested whether true interindividual variability exists for changes in insulin sensitivity and glyceamic control following 6-weeks of low volume sprint interval training (SIT).The high level of technical, biological, and random error associated with repeated measurements of insulin sensitivity and glycaemic control, means we can neither confidently conclude that there is evidence of true interindividual differences in the trainability of these outcomes following SIT, nor confidently identify responders or non-responders for such parameters.Researchers contrasting responders vs. non-responders for a given parameter, either to understand mechanisms of adaptation and/or develop physiological/genetic/epigenetic predictors of response, need to be aware that identification of responders and non-responders with sufficient certainty may not be achievable for parameters with a high level of technical, biological, and random error.

Interindividual Differences in Trainability and Moderators of Cardiorespiratory Fitness, Waist Circumference, and Body Mass Responses: A Large-Scale Individual Participant Data Meta-analysis.

Although many studies have assumed variability reflects variance caused by exercise training, few studies have examined whether interindividual differences in trainability are present following exercise training. The present individual participant data (IPD) meta-analysis sought to: (1) investigate the presence of interindividual differences in trainability for cardiorespiratory fitness (CRF), waist circumference, and body mass; and (2) examine the influence of exercise training and potential moderators on the probability that an individual will experience clinically important differences. The IPD meta-analysis combined data from 1879 participants from eight previously published randomized controlled trials. We implemented a Bayesian framework to: (1) test the hypothesis of interindividual differences in trainability by comparing variability in change scores between exercise and control using Bayes factors; and (2) compare posterior predictions of control and exercise across a range of moderators (baseline body mass index (BMI) and exercise duration, intensity, amount, mode, and adherence) to estimate the proportions of participants expected to exceed minimum clinically important differences (MCIDs) for all three outcomes. Bayes factors demonstrated a lack of evidence supporting a high degree of variance attributable to interindividual differences in trainability across all three outcomes. These findings indicate that interindividual variability in observed changes are likely due to measurement error and external behavioural factors, not interindividual differences in trainability. Additionally, we found that a larger proportion of exercise participants were expected to exceed MCIDs compared with controls for all three outcomes. Moderator analyses identified that larger proportions were associated with a range of factors consistent with standard exercise theory and were driven by mean changes. Practitioners should prescribe exercise interventions known to elicit large mean changes to increase the probability that individuals will experience beneficial changes in CRF, waist circumference and body mass.

Change in Central Cardiovascular Function in Response to Intense Interval Training: A Systematic Review and Meta-analysis.

INTRODUCTION: High-intensity interval training and sprint interval training significantly increase maximal oxygen uptake (V̇O 2max ), which enhances endurance performance and health status. Whether this response is due to increases in central cardiovascular function (cardiac output (CO) and blood volume) or peripheral factors is unknown. PURPOSE: This study aimed to conduct a systematic review and meta-analysis to assess the effects of high-intensity interval training and sprint interval training (referred to as intense interval training) on changes in central cardiovascular function. METHODS: We performed a systematic search of eight databases for studies denoting increases in V̇O 2max in which CO, stroke volume (SV), blood volume, plasma volume, end-diastolic/systolic volume, or hematocrit were measured. RESULTS: Forty-five studies were included in this analysis, comprising 946 men and women of various health status (age and V̇O 2max , 20-76 yr and 13-61 mL·kg -1 ·min -1 ) who performed 6-96 sessions of interval training. Results showed an increase in V̇O 2max with intense interval training that was classified as a large effect ( d = 0.83). SV ( d = 0.69), and CO ( d = 0.49) had moderate effect sizes in response to intense interval training. Of 27 studies in which CO was measured, 77% exhibited significant increases in resting CO or that obtained during exercise. Similarly, 93% of studies revealed significant increases in SV in response to intense interval training. Effect sizes for these outcomes were larger for clinical versus healthy populations. Plasma volume, blood volume, and hematocrit had small effect sizes after training ( d = 0.06-0.14). CONCLUSIONS: Increases in V̇O 2max demonstrated with intense interval training are attendant with increases in central O 2 delivery with little contribution from changes in hematocrit, blood volume, or plasma volume.

Subcutaneous adipose tissue sclerostin is reduced and Wnt signaling is enhanced following 4-weeks of sprint interval training in young men with obesity.

Sclerostin is a Wnt/ß-catenin antagonist, mainly secreted by osteocytes, and most known for its role in reducing bone formation. Studies in rodents suggest sclerostin can also regulate adipose tissue mass and metabolism, representing bone-adipose tissue crosstalk. Exercise training has been shown to reduce plasma sclerostin levels; but the effects of exercise on sclerostin and Wnt/ß-catenin signaling specifically within adipose tissue has yet to be examined. The purpose of this study was to examine subcutaneous WAT (scWAT) sclerostin content and Wnt signaling in response to exercise training in young men with obesity. To this end, 7 male participants (BMI = 35 ± 4; 25 ± 4 years) underwent 4 weeks of sprint interval training (SIT) involving 4 weekly sessions consisting of a 5-min warmup, followed by 8 × 20 s intervals at 170% of work rate at VO2peak , separated by 10 s of rest. Serum and scWAT were sampled at rest both pre- and post-SIT. Despite no changes in serum sclerostin levels, we found a significant decrease in adipose sclerostin content (-37%, p = 0.04), an increase in total ß-catenin (+52%, p = 0.03), and no changes in GSK3ß serine 9 phosphorylation. There were also concomitant reductions in serum TNF-α (-0.36 pg/ml, p = 0.03) and IL-6 (-1.44 pg/ml, p = 0.05) as well as an increase in VO2peak (+5%, p = 0.03) and scWAT COXIV protein content (+95%, p = 0.04). In conclusion, scWAT sclerostin content was reduced and ß-catenin content was increased following SIT in young men with excess adiposity, suggesting a role of sclerostin in regulating human adipose tissue in response to exercise training.

Risk of bias and reporting practices in studies comparing VO2max responses to sprint interval vs. continuous training: A systematic review and meta-analysis.

BACKGROUND: It remains unclear whether studies comparing maximal oxygen uptake (VO2max) response to sprint interval training (SIT) vs. moderate-intensity continuous training (MICT) are associated with a high risk of bias and poor reporting quality. The purpose of this study was to evaluate the risk of bias and quality of reporting in studies comparing changes in VO2max between SIT and MICT. METHODS: We conducted a comprehensive literature search of 4 major databases: AMED, CINAHL, EMBASE, and MEDLINE. Studies were excluded if participants were not healthy adult humans or if training protocols were unsupervised, lasted less than 2 weeks, or utilized mixed exercise modalities. We used the Cochrane Collaboration tool and the CONSORT checklist for non-pharmacological trials to evaluate the risk of bias and reporting quality, respectively. RESULTS: Twenty-eight studies with 30 comparisons (3 studies included 2 SIT groups) were included in our meta-analysis (n = 360 SIT participants: body mass index (BMI) = 25.9 ± 3.7 kg/m2, baseline VO2max = 37.9 ± 8.0 mL/kg/min; n = 359 MICT participants: BMI = 25.5 ± 3.8 kg/m2, baseline VO2max = 38.3 ± 8.0 mL/kg/min; all mean ± SD). All studies had an unclear risk of bias and poor reporting quality. CONCLUSION: Although we observed a lack of superiority between SIT and MICT for improving VO2max (weighted Hedge's g = -0.004, 95% confidence interval (95%CI): -0.08 to 0.07), the overall unclear risk of bias calls the validity of this conclusion into question. Future studies using robust study designs are needed to interrogate the possibility that SIT and MICT result in similar changes in VO2max.

Directions for Exercise Treatment Response Heterogeneity and Individual Response Research.

Treatment response heterogeneity and individual responses following exercise training are topics of interest for personalized medicine. Proposed methods to determine the contribution of exercise to the magnitude of treatment response heterogeneity and categorizing participants have expanded and evolved. Setting clear research objectives and having a comprehensive understanding of the strengths and weaknesses of the available methods are vital to ensure the correct study design and analytical approach are used. Doing so will ensure contributions to the field are conducted as rigorously as possible. Nonetheless, concerns have emerged regarding the ability to truly isolate the impact of exercise training, and the nature of individual responses in relation to mean group changes. The purpose of this review is threefold. First, the strengths and limitations associated with current methods for quantifying the contribution of exercise to observed treatment response heterogeneity will be discussed. Second, current methods used to categorize participants based on their response to exercise will be outlined, as well as proposed mechanisms for factors that contribute to response variation. Finally, this review will provide an overview of some current issues at the forefront of individual response research.

A Systematic Review Examining the Approaches Used to Estimate Interindividual Differences in Trainability and Classify Individual Responses to Exercise Training.

Background: Many reports describe statistical approaches for estimating interindividual differences in trainability and classifying individuals as "responders" or "non-responders." The extent to which studies in the exercise training literature have adopted these statistical approaches remains unclear. Objectives: This systematic review primarily sought to determine the extent to which studies in the exercise training literature have adopted sound statistical approaches for examining individual responses to exercise training. We also (1) investigated the existence of interindividual differences in trainability, and (2) tested the hypothesis that less conservative thresholds inflate response rates compared with thresholds that consider error and a smallest worthwhile change (SWC)/minimum clinically important difference (MCID). Methods: We searched six databases: AMED, CINAHL, EMBASE, Medline, PubMed, and SportDiscus. Our search spanned the aerobic, resistance, and clinical or rehabilitation training literature. Studies were included if they used human participants, employed standardized and supervised exercise training, and either: (1) stated that their exercise training intervention resulted in heterogenous responses, (2) statistically estimated interindividual differences in trainability, and/or (3) classified individual responses. We calculated effect sizes (ESIR) to examine the presence of interindividual differences in trainability. We also compared response rates (n = 614) across classification approaches that considered neither, one of, or both errors and an SWC or MCID. We then sorted response rates from studies that also reported mean changes and response thresholds (n = 435 response rates) into four quartiles to confirm our ancillary hypothesis that larger mean changes produce larger response rates. Results: Our search revealed 3,404 studies, and 149 were included in our systematic review. Few studies (n = 9) statistically estimated interindividual differences in trainability. The results from these few studies present a mixture of evidence for the presence of interindividual differences in trainability because several ESIR values lay above, below, or crossed zero. Zero-based thresholds and larger mean changes significantly (both p < 0.01) inflated response rates. Conclusion: Our findings provide evidence demonstrating why future studies should statistically estimate interindividual differences in trainability and consider error and an SWC or MCID when classifying individual responses to exercise training. Systematic Review Registration: [website], identifier [registration number].

Intramuscular hematoma of the vastus lateralis following percutaneous skeletal muscle microbiopsy: a case report.

Recently, percutaneous microbiopsy needles have been used as a less invasive alternative to the Bergstrom needle for obtaining human skeletal muscle biopsy to assess changes in protein content, gene expression, and enzymatic activities. Unlike the Bergstrom muscle biopsy procedure, potential complications associated with microbiopsies of human skeletal muscle have not been documented. Therefore, the present case report follows a young male's recovery from a muscle biopsy-induced hemorrhage/hematoma of the right vastus lateralis with the specific aims of (1) informing future participants, researchers, and clinicians on expected time course of recovery and (2) informing methods to minimize future participant adverse event risk during and after the percutaneous microbiopsy procedure. The present case report demonstrates that the inadvertent hemorrhaging of a neighboring vessel by percutaneous microbiopsy procedure can be debilitating. To minimize the risk of muscle biopsy-induced hemorrhage/hematoma, we advise post-biopsy compression for up to 15 min and post-biopsy follow-up should be completed for up to 72 h. When there is indication of hematoma development, compression should be applied, and the participant should avoid exercise and physical activity.

Genome wide association study of response to interval and continuous exercise training: the Predict-HIIT study.

BACKGROUND: Low cardiorespiratory fitness (V̇O2peak) is highly associated with chronic disease and mortality from all causes. Whilst exercise training is recommended in health guidelines to improve V̇O2peak, there is considerable inter-individual variability in the V̇O2peak response to the same dose of exercise. Understanding how genetic factors contribute to V̇O2peak training response may improve personalisation of exercise programs. The aim of this study was to identify genetic variants that are associated with the magnitude of V̇O2peak response following exercise training. METHODS: Participant change in objectively measured V̇O2peak from 18 different interventions was obtained from a multi-centre study (Predict-HIIT). A genome-wide association study was completed (n = 507), and a polygenic predictor score (PPS) was developed using alleles from single nucleotide polymorphisms (SNPs) significantly associated (P < 1 × 10-5) with the magnitude of V̇O2peak response. Findings were tested in an independent validation study (n = 39) and compared to previous research. RESULTS: No variants at the genome-wide significance level were found after adjusting for key covariates (baseline V̇O2peak, individual study, principal components which were significantly associated with the trait). A Quantile-Quantile plot indicates there was minor inflation in the study. Twelve novel loci showed a trend of association with V̇O2peak response that reached suggestive significance (P < 1 × 10-5). The strongest association was found near the membrane associated guanylate kinase, WW and PDZ domain containing 2 (MAGI2) gene (rs6959961, P = 2.61 × 10-7). A PPS created from the 12 lead SNPs was unable to predict V̇O2peak response in a tenfold cross validation, or in an independent (n = 39) validation study (P > 0.1). Significant correlations were found for beta coefficients of variants in the Predict-HIIT (P < 1 × 10-4) and the validation study (P < × 10-6), indicating that general effects of the loci exist, and that with a higher statistical power, more significant genetic associations may become apparent. CONCLUSIONS: Ongoing research and validation of current and previous findings is needed to determine if genetics does play a large role in V̇O2peak response variance, and whether genomic predictors for V̇O2peak response trainability can inform evidence-based clinical practice. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR), Trial Id: ACTRN12618000501246, Date Registered: 06/04/2018, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374601&isReview=true .

Examining interindividual differences in select muscle and whole-body adaptations to continuous endurance training.

NEW FINDINGS: What is the central question of the study? Do interindividual differences in trainability exist for morphological and molecular skeletal muscle responses to aerobic exercise training? What is the main finding and its importance? Interindividual differences in trainability were present for some, but not all, morphological and molecular outcomes included in our study. Our findings suggest that it is inappropriate, and perhaps erroneous, to assume that variability in observed responses reflects interindividual differences in trainability in skeletal muscle responses to aerobic exercise training. ABSTRACT: Studies have interpreted a wide range of morphological and molecular changes in human skeletal muscle as evidence of interindividual differences in trainability. However, these interpretations fail to account for the influence of random measurement error and within-subject variability. The purpose of the present study was to use the standard deviation of individual response (SDIR ) statistic to test the hypothesis that interindividual differences in trainability are present for some but not all skeletal muscle outcomes. Twenty-nine recreationally active males (age: 21 ± 2 years; BMI: 24 ± 3 kg/m2 ; V̇O2peak ; 45 ± 7 ml/kg/min) completed 4 weeks of continuous training (REL; n = 14) or control (n = 15). Maximal enzyme activities (citrate synthase and ß-hydroxyacyl-CoA dehydrogenase), capillary density, fibre type composition, fibre-specific succinate dehydrogenase activity and substrate storage (intramuscular triglycerides and glycogen), and markers of mitophagy (BCL2-interacting protein 3 (BNIP3), BNIP3-like protein, parkin and PTEN-induced kinase 1) were measured in vastus lateralis samples collected before and after the intervention. We also calculated SDIR values for V̇O2peak , peak work rate and the onset of blood lactate accumulation for the REL group and a separate group that exercised at the negative talk test stage. Although positive SDIR values - indicating interindividual differences in trainability - were obtained for aerobic capacity outcomes, maximal enzyme activities, capillary density, all fibre-specific outcomes and BNIP3 protein content, the remaining outcomes produced negative SDIR values indicating a large degree of random measurement error and/or within-subject variability. Our findings question the interpretation of heterogeneity in observed responses as evidence of interindividual differences in trainability and highlight the importance of including control groups when analysing individual skeletal muscle response to exercise training.

Can non-responders be 'rescued' by increasing exercise intensity? A quasi-experimental trial of individual responses among humans living with pre-diabetes or type 2 diabetes mellitus in Canada.

INTRODUCTION: Exercise is recommended to improve glycaemic control. Yet, individual changes in glycaemic control following exercise can vary greatly, meaning while some significantly improve others, coined 'non-responders', do not. Increasing the intensity of exercise may 'rescue' non-responders and help generate a response to training. This trial will identify non-responders to changes in glycated haemoglobin (HbA1c) across inactive individuals living with pre-diabetes or type 2 diabetes mellitus following an aerobic exercise programme and evaluate if increasing training intensity will elicit beneficial changes to 'rescue' previously categorised non-responders. METHODS AND ANALYSIS: This study will recruit 60 participants for a two-phase aerobic exercise training programme. Participants will be allocated to a control group or assigned to an intervention group. Control participants will maintain their current lifestyle habits. During phase 1, intervention participants will complete 16 weeks of aerobic exercise at an intensity of 4.5 metabolic equivalents (METs) for 150 min per week. Participants will then be categorised as responders or non-responders based on the change in HbA1c. For phase 2, participants will be blocked based on responder status and randomly allocated to a maintained intensity, or increased intensity group for 12 weeks. The maintained group will continue to train at 4.5 METs, while the increased intensity group will train at 6.0 METs for 150 min per week. ETHICS AND DISSEMINATION: Results will be presented at scientific meetings and submitted to peer-reviewed journals. Publications and presentations related to the study will be authorised and reviewed by all investigators. Findings from this study will be used to provide support for future randomised control trials. All experimental procedures have been approved by the Research Ethics Board at the University of New Brunswick (REB: 2018-168). TRIAL REGISTRATION NUMBER: NCT03787836.