Effects of heavy-load strength training during (neo-)adjuvant chemotherapy on muscle strength, muscle fiber size, myonuclei, and satellite cells in women with breast cancer.

To investigate the effects of heavy-load strength training during (neo-)adjuvant chemotherapy in women with breast cancer on muscle strength, body composition, muscle fiber size, satellite cells, and myonuclei. Women with stage I-III breast cancer were randomly assigned to a strength training group (ST, n = 23) performing supervised heavy-load strength training twice a week during chemotherapy, or a usual care control group (CON, n = 17). Muscle strength and body composition were measured and biopsies from m. vastus lateralis collected before the first cycle of chemotherapy (T0) and after chemotherapy and training (T1). Muscle strength increased significantly more in ST than in CON in chest-press (ST: +10 ± 8%, p < .001, CON: -3 ± 5%, p = .023) and leg-press (ST: +11 ± 8%, p < .001, CON: +3 ± 6%, p = .137). Both groups reduced fat-free mass (ST: -4.9 ± 4.0%, p < .001, CON: -5.2 ± 4.9%, p = .004), and increased fat mass (ST: +15.3 ± 16.5%, p < .001, CON: +16.3 ± 19.8%, p = .015) with no significant differences between groups. No significant changes from T0 to T1 and no significant differences between groups were observed in muscle fiber size. For myonuclei per fiber a non-statistically significant increase in CON and a non-statistically significant decrease in ST in type I fibers tended (p = .053) to be different between groups. Satellite cells tended to decrease in ST (type I: -14 ± 36%, p = .097, type II: -9 ± 55%, p = .084), with no changes in CON and no differences between groups. Strength training during chemotherapy improved muscle strength but did not significantly affect body composition, muscle fiber size, numbers of satellite cells, and myonuclei compared to usual care.

Muscle memory in humans: evidence for myonuclear permanence and long-term transcriptional regulation after strength training.

The objective of this work was to investigate myonuclear permanence and transcriptional regulation as mechanisms for cellular muscle memory after strength training in humans. Twelve untrained men and women performed 10 weeks of unilateral elbow-flexor strength training followed by 16 weeks of de-training. Thereafter, 10 weeks' re-training was conducted with both arms: the previously trained arm and the contralateral untrained control arm. Muscle biopsies were taken from the trained arm before and after both training periods and from the control arm before and after re-training. Muscle biopsies were analysed for fibre cross-sectional area (fCSA), myonuclei and global transcriptomics (RNA sequencing). During the first training period, myonuclei increased in type 1 (13 ± 17%) and type 2 (33 ± 23%) fibres together with a 30 ± 43% non-significant increase in mixed fibre fCSA (P = 0.069). Following de-training, fCSA decreased in both fibre types, whereas myonuclei were maintained, resulting in 33% higher myonuclear number in previously trained vs. control muscle in type 2 fibres. Furthermore, in the previously trained muscle, three differentially expressed genes (DEGs; EGR1, MYL5 and COL1A1) were observed. Following re-training, the previously trained muscle showed larger type 2 fCSA compared to the control (P = 0.035). However, delta change in type 2 fCSA was not different between muscles. Gene expression was more dramatically changed in the control arm (1338 DEGs) than in the previously trained arm (822 DEGs). The sustained higher number of myonuclei in the previously trained muscle confirms myonuclear accretion and permanence in humans. Nevertheless, because of the unclear effect on the subsequent hypertrophy with re-training, the physiological benefit remains to be determined. KEY POINTS: Muscle memory is a cellular mechanism that describes the capacity of skeletal muscle fibres to respond differently to training stimuli if the stimuli have been previously encountered. This study overcomes past methodological limitations related to the choice of muscles and analytical procedures. We show that myonuclear number is increased after strength training and maintained during de-training. Increased myonuclear number and differentially expressed genes related to muscle performance and development in the previously trained muscle did not translate into a clearly superior responses during re-training. Because of the unclear effect on the subsequent hypertrophy and muscle strength gain with re-training, the physiological benefit remains to be determined.

Aerobic exercise training resets the human skeletal muscle methylome 10 years after breast cancer treatment and survival.

Cancer survivors suffer impairments in skeletal muscle in terms of reduced mass and function. Interestingly, human skeletal muscle possesses an epigenetic memory of earlier stimuli, such as exercise. Long-term retention of epigenetic changes in skeletal muscle following cancer survival and/or exercise training has not yet been studied. We, therefore, investigated genome-wide DNA methylation (methylome) in skeletal muscle following a 5-month, 3/week aerobic-training intervention in breast cancer survivors 10-14 years after diagnosis and treatment. These results were compared to breast cancer survivors who remained untrained and to age-matched controls with no history of cancer, who undertook the same training intervention. Skeletal muscle biopsies were obtained from 23 females before(pre) and after(post) the 5-month training period. InfiniumEPIC 850K DNA methylation arrays and RT-PCR for gene expression were performed. The breast cancer survivors displayed a significant retention of increased DNA methylation (i.e., hypermethylation) at a larger number of differentially methylated positions (DMPs) compared with healthy age-matched controls pre training. Training in cancer survivors led to an exaggerated number of DMPs with a hypermethylated signature occurring at non-regulatory regions compared with training in healthy age-matched controls. However, the opposite occurred in important gene regulatory regions, where training in cancer survivors elicited a considerable reduction in methylation (i.e., hypomethylation) in 99% of the DMPs located in CpG islands within promoter regions. Importantly, training was able to reverse the hypermethylation identified in cancer survivors back toward a hypomethylated signature that was observed pre training in healthy age-matched controls at 300 (out of 881) of these island/promoter-associated CpGs. Pathway enrichment analysis identified training in cancer survivors evoked a predominantly hypomethylated signature in pathways associated with cell cycle, DNA replication/repair, transcription, translation, mTOR signaling, and the proteosome. Differentially methylated region (DMR) analysis also identified genes: BAG1, BTG2, CHP1, KIFC1, MKL2, MTR, PEX11B, POLD2, S100A6, SNORD104, and SPG7 as hypermethylated in breast cancer survivors, with training reversing these CpG island/promoter-associated DMRs toward a hypomethylated signature. Training also elicited a largely different epigenetic response in healthy individuals than that observed in cancer survivors, with very few overlapping changes. Only one gene, SIRT2, was identified as having altered methylation in cancer survivors at baseline and after training in both the cancer survivors and healthy controls. Overall, human skeletal muscle may retain a hypermethylated signature as long as 10-14 years after breast cancer treatment/survival. Five months of aerobic training reset the skeletal muscle methylome toward signatures identified in healthy age-matched individuals in gene regulatory regions.

Transdermal oestradiol and exercise in androgen deprivation therapy (ESTRACISE): protocol.

OBJECTIVE: To report the protocol of a study evaluating the efficacy of transdermal oestradiol (E2) gel in reducing the adverse effects of androgen deprivation therapy (ADT), specifically on sexual function, and to assess the utility of E2 in combination with supervised exercise. STUDY DESIGN AND METHODS: The primary endpoint of this open-label Phase IIA randomized controlled trial is the efficacy of transdermal E2 gel. Secondary endpoints include: (i) the occurrence of ADT-induced adverse effects; (ii) the safety and tolerability of E2; (iii) the impact of E2 with or without exercise on physical, physiological, muscle, and systemic biomarkers; and (iv) quality of life. The trial will recruit high-risk PCa patients (n = 310) undergoing external beam radiation therapy with adjuvant subcutaneous ADT. Participants will be stratified and randomized in a 1:1 ratio to either the E2 + ADT arm or the ADT-only control arm. Additionally, a subset of patients (n = 120) will be randomized into a supervised exercise programme. RESULTS: The primary outcome is assessed according to the efficacy of E2 in mitigating the deterioration of Expanded Prostate Cancer Index Composite sexual function domain scores. Secondary outcomes are assessed according to the occurrence of ADT-induced adverse effects, safety and tolerability of E2, impact of E2 with or without exercise on physical performance, body composition, bone mineral density, muscle size, systematic biomarkers, and quality of life. CONCLUSION: The ESTRACISE study's innovative design can offer novel insights about the benefits of E2 gel, and the substudy can reinforce the benefits resistance training and deliver valuable new novel insights into the synergistic benefits of E2 gel and exercise, which are currently unknown. TRIAL REGISTRATION: The protocol has been registered in euclinicaltrials.eu (2023-504704-28-00) and in clinicaltrials.gov (NCT06271551).

Superiority of High-Load vs. Low-Load Resistance Training in Military Cadets.

ABSTRACT: Øfsteng, SF, Hammarström, D, Knox, S, Jøsok, Ø, Helkala, K, Koll, L, Hanestadhaugen, M, Raastad, T, Rønnestad, BR, and Ellefsen, S. Superiority of high-load vs. low-load resistance training in military cadets. J Strength Cond Res 38(9): 1584-1595, 2024-Muscle strength and power are important determinants of soldiers' performance in modern warfare. Here, we compare the efficacy of 22 weeks of whole-body resistance training with high load (HL, 10 repetitions maximum/RM) and low load (LL, 30RM) for developing maximal muscle strength and power, performance, and muscle mass in moderately trained cadets (20 ± 1 year, f; n = 5, m; n = 22). Outcome measures were assessed at baseline and at week 22, in addition to a mid-intervention assessment at week 10. Twenty-two weeks of HL led to greater increases in muscle strength (upper limb, Δ 10%, 95% CI [2.8, 17.1], p = 0.01; lower limb, Δ 9.9%, CI [1.1, 18.6], p = 0.029), jump height (Δ 5.5%, CI [1.4, 9.6], p = 0.011), and upper limb lean mass (Δ 5.2%, CI [1, 9.4], p = 0.018) compared with LL. HL and LL led to similar changes in agility, muscle endurance performance, lower limb muscle mass, and cross-sectional area in m. vastus lateralis. For all variables, training-associated changes occurred primarily during the initial 10 weeks of the intervention, including the differential responses to HL and LL. In conclusion, although 22 weeks of HL led to greater increases in lower and upper limb muscle strength, power, and upper limb lean mass than LL, the 2 load conditions led to similar improvements in agility performance and lower limb muscle mass. Our results thus indicate that both loading regimes elicit multifaceted physiological improvements important for military readiness.

Pre-treatment levels of inflammatory markers and chemotherapy completion rates in patients with early-stage breast cancer.

BACKGROUND: Chemotherapy efficacy is largely dependent on treatment adherence, defined by the relative dose intensity (RDI). Identification of new modifiable risk factors associated with low RDI might improve chemotherapy delivery. Here, we evaluated the association between low RDI and pre-chemotherapy factors, including patient- and treatment-related characteristics and markers of inflammation. METHODS: This exploratory analysis assessed data from 267 patients with early-stage breast cancer scheduled to undergo (neo-)adjuvant chemotherapy included in the Physical training and Cancer (Phys-Can) trial. The association between low RDI, defined as < 85%, patient-related (age, body mass index, co-morbid condition, body surface area) and treatment-related factors (cancer stage, receptor status, chemotherapy duration, chemotherapy dose, granulocyte colony-stimulating factor) was investigated. Analyses further included the association between RDI and pre-chemotherapy levels of interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP) and Tumor Necrosis Factor-alpha (TNF-α) in 172 patients with available blood samples. RESULTS: An RDI of < 85% occurred in 31 patients (12%). Univariable analysis revealed a significant association with a chemotherapy duration above 20 weeks (p < 0.001), chemotherapy dose (p = 0.006), pre-chemotherapy IL-8 (OR 1.61; 95% CI (1.01; 2.58); p = 0.040) and TNF-α (OR 2.2 (1.17; 4.53); p = 0.019). In multivariable analyses, inflammatory cytokines were significant association with low RDI for IL-8 (OR: 1.65 [0.99; 2.69]; p = 0.044) and TNF-α (OR 2.95 [1.41; 7.19]; p = 0.007). CONCLUSIONS: This exploratory analysis highlights the association of pre-chemotherapy IL-8 and TNF-α with low RDI of chemotherapy for breast cancer. IL-8 and TNF-α may therefore potentially help to identify patients at risk for experiencing dose reductions. Clinical trial number NCT02473003 (registration: June 16, 2015).

Comparison of methods to identify individuals with obesity at increased risk of functional impairment among a population of home-dwelling older adults.

Obesity is associated with increased muscle mass and muscle strength. Methods taking into account the total body mass to reveal obese older individuals at increased risk of functional impairment are needed. Therefore, we aimed to detect methods to identify obese older adults at increased risk of functional impairment. Home-dwelling older adults (n 417, ≥ 70 years of age) were included in this cross-sectional study. Sex-specific cut-off points for two obesity phenotypes (waist circumference (WC) and body fat mass (FM %)) were used to divide women and men into obese and non-obese groups, and within-sex comparisons were performed. Obese women and men, classified by both phenotypes, had similar absolute handgrip strength (HGS) but lower relative HGS (HGS/total body mass) (P < 0·001) than non-obese women and men, respectively. Women with increased WC and FM %, and men with increased WC had higher appendicular skeletal muscle mass (P < 0·001), lower muscle quality (HGS/upper appendicular muscle mass) (P < 0·001), and spent longer time on the stair climb test and the repeated sit-to-stand test (P < 0·05) than non-obese women and men, respectively. Absolute muscle strength was not able to discriminate between obese and non-obese older adults. However, relative muscle strength in particular, but also muscle quality and physical performance tests, where the total body mass was taken into account or served as an extra load, identified obese older adults at increased risk of functional impairment. Prospective studies are needed to determine clinically relevant cut-off points for relative HGS in particular.

Muscular heat shock protein response and muscle damage after semi-professional football match.

PURPOSE: A typical football match leads to neuromuscular fatigue and physical performance impairments up to 72-96 h post-match. While muscle damage is thought to be a major factor, damage on the ultrastructural level has never been documented. The purpose of this study was to investigate post-match cellular muscle damage by quantifying the heat shock protein (HSP) response as a proxy for protein damage. METHODS: Muscle biopsies, blood samples, countermovement jumps, and perception of muscle soreness were obtained from twelve semi-professional football players 1, 24, 48, and 72 h after a 90-min football match. Muscle biopsies were analyzed for αB-crystallin and HSP70 in the cytosolic and cytoskeletal sub-cellular fractions by Western blotting. Fiber type-specific αB-crystallin and HSP70 staining intensity, and tenascin-C immunoreactivity were analyzed with immunohistochemistry. Blood samples were analyzed for creatine kinase and myoglobin. RESULTS: Within 24 h post-match, a 2.7- and 9.9-fold increase in creatine kinase and myoglobin were observed, countermovement jump performance decreased by -9.7% and muscle soreness increased by 0.68 units. αB-crystallin and HSP70 accumulated in cytoskeletal structures evident by a 3.6- and 1.8-fold increase in the cytoskeletal fraction and a parallel decrease in the cytosolic fraction. In type I and II fibers, αB-crystallin staining intensity increased by 15%-41% and remained elevated at 72 h post-match. Lastly, the percentage of fibers with granular staining of αB-crystallin increased 2.2-fold. CONCLUSIONS: Football match play induced a muscular HSP stress response 1-72 h post-match. Specifically, the accumulation of HSPs in cytoskeletal structures and the granular staining of αB-crystallin suggests occurrence of ultrastructural damage. The damage, indicated by the HSP response, might be one reason for the typically 72 h decrease in force-generating capacity after football matches.

Technical match actions and plasma stress markers in elite female football players during an official FIFA Tournament.

This study analyzed the impact of performing four consecutive football matches separated by 48-72 hours during a FIFA tournament on physical load, technical performance and plasma markers of redox state, muscle damage and inflammation in elite female players. Forty-eight players from three national teams were evaluated at seven time points: before (baseline) and throughout the tournament (after each match and before two training sessions). Only data from players who played all matches were included in the analyses (N = 13). The players were divided into high-rank (N = 6) and low-rank (N = 7) team players according to FIFA standards. Plasma creatine kinase (CK), C-reactive protein (CRP), total antioxidant status (TAS), and uric acid (UA) were analyzed at the selected time points. Technical performance and physical load were also quantified according to team rank. Players from low-rank teams played significantly more time than high-rank players (85 ± 10 vs 67 ± 15 minutes; P = .02; d = 1.51). Low-rank team players presented higher values in technical performance actions than the high-rank team players, but most of the differences were explained by the longer match time played. UA content differed across the matches, increasing from baseline (F(4,40)  = 3.90; P = .01) and more in the high-rank team players (F(1,10)  = 20.46; P = .001), while CRP only differed across the matches (F(4,36)  = 2.66; P = .05), also increasing from baseline. A large time effect was shown for UA only in the high-rank players (η2 p  = 0.50; P = .02). Four consecutive matches did not result in considerable alterations in plasma stress markers, physical load, and technical performance in elite female football players from distinct rank levels.

Chronic obstructive pulmonary disease does not impair responses to resistance training.

BACKGROUND: Subjects with chronic obstructive pulmonary disease (COPD) are prone to accelerated decay of muscle strength and mass with advancing age. This is believed to be driven by disease-inherent systemic pathophysiologies, which are also assumed to drive muscle cells into a state of anabolic resistance, leading to impaired abilities to adapt to resistance exercise training. Currently, this phenomenon remains largely unstudied. In this study, we aimed to investigate the assumed negative effects of COPD for health- and muscle-related responsiveness to resistance training using a healthy control-based translational approach. METHODS: Subjects with COPD (n = 20, GOLD II-III, FEV1predicted 57 ± 11%, age 69 ± 5) and healthy controls (Healthy, n = 58, FEV1predicted 112 ± 16%, age 67 ± 4) conducted identical whole-body resistance training interventions for 13 weeks, consisting of two weekly supervised training sessions. Leg exercises were performed unilaterally, with one leg conducting high-load training (10RM) and the contralateral leg conducting low-load training (30RM). Measurements included muscle strength (nvariables = 7), endurance performance (nvariables = 6), muscle mass (nvariables = 3), muscle quality, muscle biology (m. vastus lateralis; muscle fiber characteristics, RNA content including transcriptome) and health variables (body composition, blood). For core outcome domains, weighted combined factors were calculated from the range of singular assessments. RESULTS: COPD displayed well-known pathophysiologies at baseline, including elevated levels of systemic low-grade inflammation ([c-reactive protein]serum), reduced muscle mass and functionality, and muscle biological aberrancies. Despite this, resistance training led to improved lower-limb muscle strength (15 ± 8%), muscle mass (7 ± 5%), muscle quality (8 ± 8%) and lower-limb/whole-body endurance performance (26 ± 12%/8 ± 9%) in COPD, resembling or exceeding responses in Healthy, measured in both relative and numeric change terms. Within the COPD cluster, lower FEV1predicted was associated with larger numeric and relative increases in muscle mass and superior relative improvements in maximal muscle strength. This was accompanied by similar changes in hallmarks of muscle biology such as rRNA-content↑, muscle fiber cross-sectional area↑, type IIX proportions↓, and changes in mRNA transcriptomics. Neither of the core outcome domains were differentially affected by resistance training load. CONCLUSIONS: COPD showed hitherto largely unrecognized responsiveness to resistance training, rejecting the notion of disease-related impairments and rather advocating such training as a potent measure to relieve pathophysiologies. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02598830. Registered November 6th 2015, https://clinicaltrials.gov/ct2/show/NCT02598830.

Frequent blood flow restricted training not to failure and to failure induces similar gains in myonuclei and muscle mass.

The purpose of the present study was to compare the effects of short-term high-frequency failure vs non-failure blood flow-restricted resistance exercise (BFRRE) on changes in satellite cells (SCs), myonuclei, muscle size, and strength. Seventeen untrained men performed four sets of BFRRE to failure (Failure) with one leg and not to failure (Non-failure; 30-15-15-15 repetitions) with the other leg using knee-extensions at 20% of one repetition maximum (1RM). Fourteen sessions were distributed over two 5-day blocks, separated by a 10-day rest period. Muscle samples obtained before, at mid-training, and 10-day post-intervention (Post10) were analyzed for muscle fiber area (MFA), myonuclei, and SC. Muscle size and echo intensity of m.rectus femoris (RF) and m.vastus lateralis (VL) were measured by ultrasonography, and knee extension strength with 1RM and maximal isometric contraction (MVC) up until Post24. Both protocols increased myonuclear numbers in type-1 (12%-17%) and type-2 fibers (20%-23%), and SC in type-1 (92%-134%) and type-2 fibers (23%-48%) at Post10 (p < 0.05). RF and VL size increased by 5%-10% in both legs at Post10 to Post24, whereas the MFA of type-1 fibers in Failure was decreased at Post10 (-10 ± 16%; p = 0.02). Echo intensity increased by ~20% in both legs during Block1 (p < 0.001) and was ~8 to 11% below baseline at Post24 (p = 0.001-0.002). MVC and 1RM decreased by 5%-10% after Block1, but increased in both legs by 6%-11% at Post24 (p < 0.05). In conclusion, both short-term high-frequency failure and non-failure BFRRE induced increases in SCs, in myonuclei content, muscle size, and strength, concomitant with decreased echo intensity. Intriguingly, the responses were delayed and peaked 10-24 days after the training intervention. Our findings may shed light on the mechanisms involved in resistance exercise-induced overreaching and supercompensation.

Does exercise intensity matter for fatigue during (neo-)adjuvant cancer treatment? The Phys-Can randomized clinical trial.

Exercise during cancer treatment improves cancer-related fatigue (CRF), but the importance of exercise intensity for CRF is unclear. We compared the effects of high- vs low-to-moderate-intensity exercise with or without additional behavior change support (BCS) on CRF in patients undergoing (neo-)adjuvant cancer treatment. This was a multicenter, 2x2 factorial design randomized controlled trial (Clinical Trials NCT02473003) in Sweden. Participants recently diagnosed with breast (n = 457), prostate (n = 97) or colorectal (n = 23) cancer undergoing (neo-)adjuvant treatment were randomized to high intensity (n = 144), low-to-moderate intensity (n = 144), high intensity with BCS (n = 144) or low-to-moderate intensity with BCS (n = 145). The 6-month exercise intervention included supervised resistance training and home-based endurance training. CRF was assessed by Multidimensional Fatigue Inventory (MFI, five subscales score range 4-20), and Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F, score range 0-52). Multiple linear regression for main factorial effects was performed according to intention-to-treat, with post-intervention CRF as primary endpoint. Overall, 577 participants (mean age 58.7 years) were randomized. Participants randomized to high- vs low-to-moderate-intensity exercise had lower physical fatigue (MFI Physical Fatigue subscale; mean difference -1.05 [95% CI: -1.85, -0.25]), but the difference was not clinically important (ie <2). We found no differences in other CRF dimensions and no effect of additional BCS. There were few minor adverse events. For CRF, patients undergoing (neo-)adjuvant treatment for breast, prostate or colorectal cancer can safely exercise at high- or low-to-moderate intensity, according to their own preferences. Additional BCS does not provide extra benefit for CRF in supervised, well-controlled exercise interventions.

Similar Morphological and Functional Training Adaptations Occur Between Continuous and Intermittent Blood Flow Restriction.

ABSTRACT: Davids, CJ, Raastad, T, James, L, Gajanand, T, Smith, E, Connick, M, McGorm, H, Keating, S, Coombes, JS, Peake, JM, and Roberts, LA. Similar morphological and functional training adaptations occur between continuous and intermittent blood flow restriction. J Strength Cond Res 35(7): 1784-1793, 2021-The aim of the study was to compare skeletal muscle morphological and functional outcomes after low-load resistance training using 2 differing blood flow restriction (BFR) protocols. Recreationally active men and women (n = 42 [f = 21], 24.4 ± 4.4 years) completed 21 sessions over 7 weeks of load-matched and volume-matched low-load resistance training (30% 1 repetition maximum [1RM]) with either (a) no BFR (CON), (b) continuous BFR (BFR-C, 60% arterial occlusion pressure [AOP]), or (c) intermittent BFR (BFR-I, 60% AOP). Muscle mass was assessed using peripheral quantitative computed tomography before and after training. Muscular strength, endurance, and power were determined before and after training by assessing isokinetic dynamometry, 1RM, and jump performance. Ratings of pain and effort were taken in the first and final training session. An alpha level of p < 0.05 was used to determine significance. There were no between-group differences for any of the morphological or functional variables. The muscle cross sectional area (CSA) increased pre-post training (p = 0.009; CON: 1.6%, BFR-C: 1.1%, BFR-I: 2.2%). Maximal isometric strength increased pre-post training (p < 0.001; CON: 9.6%, BFR-C: 14.3%, BFR-I: 19.3%). Total work performed during an isokinetic endurance task increased pre-post training (p < 0.001, CON: 3.6%, BFR-C: 9.6%, BFR-I: 11.3%). Perceptions of pain (p = 0.026) and effort (p = 0.033) during exercise were higher with BFR-C; however, these reduced with training (p = 0.005-0.034). Overall, these data suggest that when 30% 1RM loads are used with a frequency of 3 times per week, the addition of BFR does not confer superior morphological or functional adaptations in recreationally active individuals. Furthermore, the additional metabolic stress that is proposed to occur with a continuous BFR protocol does not seem to translate into proportionally greater training adaptations. The current findings promote the use of both intermittent BFR and low-load resistance training without BFR as suitable alternative training methods to continuous BFR. These approaches may be practically applicable for those less tolerable to pain and discomfort associated with ischemia during exercise.

Thromboembolic events after high-intensity training during cisplatin-based chemotherapy for testicular cancer: Case reports and review of the literature.

The randomized "Testicular cancer and Aerobic and Strength Training trial" (TAST-trial) aimed to evaluate the effect of high-intensity interval training (HIIT) on cardiorespiratory fitness during cisplatin-based chemotherapy (CBCT) for testicular cancer (TC). Here, we report on an unexpected high number of thromboembolic (TE) events among patients randomized to the intervention arm, and on a review of the literature on TE events in TC patients undergoing CBCT. Patients aged 18 to 60 years with a diagnosis of metastatic germ cell TC, planned for 3 to 4 CBCT cycles, were randomized to a 9 to 12 weeks exercise intervention, or to a single lifestyle counseling session. The exercise intervention included two weekly HIIT sessions, each with 2 to 4 intervals of 2 to 4 minutes at 85% to 95% of peak heart rate. The study was prematurely discontinued after inclusion of 19 of the planned 94 patients, with nine patients randomized to the intervention arm and 10 to the control arm. Three patients in the intervention arm developed TE complications; two with pulmonary embolism and one with myocardial infarction. All three patients had clinical stage IIA TC. No TE complications were observed among patients in the control arm. Our observations indicate that high-intensity aerobic training during CBCT might increase the risk of TE events in TC patients, leading to premature closure of the TAST-trial.

Myocellular Adaptations to Low-Load Blood Flow Restricted Resistance Training.

Low-load blood flow restricted resistance exercise (BFRRE) can stimulate whole-muscle growth and improve muscle function. However, limited knowledge exists on the effects at the myocellular level. We hypothesize that BFRRE has the ability to produce concurrent skeletal muscle myofibrillar, mitochondrial, and microvascular adaptations, thus offering an alternative strategy to counteract decay in skeletal muscle health and function in clinical populations.

Caffeine increases strength and power performance in resistance-trained females during early follicular phase.

The effects of 4 mg·kg-1 caffeine ingestion on strength and power were investigated for the first time, in resistance-trained females during the early follicular phase utilizing a randomized, double-blind, placebo-controlled, crossover design. Fifteen females (29.8 ± 4.0 years, 63.8 ± 5.5 kg [mean ± SD]) ingested caffeine or placebo 60 minutes before completing a test battery separated by 72 hours. One-repetition maximum (1RM), repetitions to failure (RTF) at 60% of 1RM, was assessed in the squat and bench press. Maximal voluntary contraction torque (MVC) and rate of force development (RFD) were measured during isometric knee extensions, while utilizing interpolated twitch technique to measure voluntary muscle activation. Maximal power and jump height were assessed during countermovement jumps (CMJ). Caffeine metabolites were measured in plasma. Adverse effects were registered after each trial. Caffeine significantly improved squat (4.5 ± 1.9%, effect size [ES]: 0.25) and bench press 1RM (3.3 ± 1.4%, ES: 0.20), and squat (15.9 ± 17.9%, ES: 0.31) and bench press RTF (9.8 ± 13.6%, ES: 0.31), compared to placebo. MVC torque (4.6 ± 7.3%, ES: 0.26), CMJ height (7.6 ± 4.0%, ES: 0.50), and power (3.8 ± 2.2%, ES: 0.24) were also significantly increased with caffeine. There were no differences in RFD or muscle activation. Plasma [caffeine] was significantly increased throughout the protocol, and mild side effects of caffeine were experienced by only 3 participants. This study demonstrated that 4 mg·kg-1 caffeine ingestion enhanced maximal strength, power, and muscular endurance in resistance-trained and caffeine-habituated females during the early follicular phase, with few adverse effects. Female strength and power athletes may consider using this dose pre-competition and -training as an effective ergogenic aid.

Sex differences in the physiological response to a demanding military field exercise.

PURPOSE: To investigate sex differences in the effect of a military field exercise on physical performance, body composition, and blood biomarkers. METHODS: Measurements were done in 23 male and 12 female conscripts before, and 0, 1, 3, 7, and 14 days after a 6-day military field exercise. RESULTS: During the field exercise, body mass decreased more in men (-6.5 ± 1.1 kg) than in women (-2.7 ± 0.7 kg), and muscle mass decreased only in men (-2.7 ± 1.0 kg). Body composition recovered within one week. Performance decreased, with no differences between men and women for countermovement jump (CMJ,-19 ± 8 vs. -18 ± 11%), medicine ball throw (MBT, -11 ± 7 vs. -11 ± 7%), and an anaerobic performance test (EVAC, -55 ± 22 vs. -47 ± 31%, men and women, respectively). MBT and EVAC performance recovered within two weeks, whereas CMJ performance was still reduced in men (-17 ± 6%) and women (-9 ± 8%) after two weeks recovery, with a larger reduction in men. Both men and women decreased [IGF-1] (-28 ± 9 vs. -41 ± 8%) and increased [cortisol] (26 ± 26 vs. 66 ± 93%, men and women, respectively) during the exercise. Most biomarkers returned to baseline values within one week. CONCLUSIONS: Men lost more body mass and muscle mass than women during a field exercise, but these differences did not lead to sex differences in changes in explosive strength and anaerobic performance. However, women recovered explosive strength in the legs faster than men.

Adaptations to strength training differ between endurance-trained and untrained women.

PURPOSE: The purpose of this study was to investigate if endurance athletes, sustaining their normal endurance training, experience attenuated adaptations to strength training compared to untrained individuals. METHODS: Eleven non-strength-trained female endurance athletes (E + S) added 11 weeks of strength training to their normal endurance training (5.1 ± 1.1 h per week), and 10 untrained women (S) performed the same strength training without any endurance training. The strength training consisted of four leg exercises [3 × 4 - 10 repetition maximum (RM)], performed twice a week for 11 weeks. RESULTS: E + S and S displayed similar increases in 1RM one-legged leg press (E + S 39 ± 19%, S 42 ± 17%, p < 0.05), maximal isometric torque in knee extension (E + S 12 ± 11%, S 8 ± 10%, p < 0.05) and lean mass in the legs (E + S 3 ± 4%, S 3 ± 3%, p < 0.05). However, S displayed superior increases in peak torque in knee extension at an angular velocity of 240° sec-1 (E + S 8 ± 5%, S 15 ± 7%, p < 0.05) and maximal squat jump height (E + S 8 ± 6%, S 14 ± 7%, p < 0.05). CONCLUSIONS: In this study, concurrent training did not impair the adaptations in the ability to develop force at low contraction velocities or muscle hypertrophy. However, concurrent training attenuated strength training-associated changes in the ability to develop force at higher muscular contraction velocities.

Strength training and protein supplementation improve muscle mass, strength, and function in mobility-limited older adults: a randomized controlled trial.

BACKGROUND: Adaptation to strength training in very old mobility-limited individuals is not fully characterized. Therefore, the aim of this study was to perform a thorough investigation of the adaptation to a lower body strength training regime in this population, with particular emphasis on the relationship between changes in selected variables. METHODS: Twenty-two mobility-limited older men and women (85 ± 6 years) were randomized to either a group performing 30 min of heavy-load strength training three times a week, with daily protein supplementation, for 10 weeks (ST), or a control group. End points were leg lean mass assessed by DXA, muscle thickness assessed by ultrasound, isometric and dynamic strength, rate of torque development, and functional capacity. RESULTS: Leg lean mass increased from baseline in ST (0.7 ± 0.3 kg), along with increased thickness of vastus lateralis (4.4 ± 3.2%), rectus femoris (6.7 ± 5.1%), and vastus intermedius (5.8 ± 5.9%). The hypertrophy was accompanied by improved knee extensor strength (20-23%) and functional performance (7-11%). In ST, neither the change in leg lean mass nor muscle thickness correlated with changes in muscle strength. However, a strong correlation was observed between the change in isometric strength and gait velocity (r = 0.70). CONCLUSIONS: The mismatch between gains in muscle size and strength suggests that muscle quality-related adaptations contributed to the increases in strength. The correlations observed between improvements in strength and function suggests that interventions eliciting large improvements in strength may also be superior in terms of functional gains in this population.

Relation between testosterone levels and body composition, physical functioning and selected biochemical parameters in adult males.

INTRODUCTION: The objective of the study was to examine the relationship between the values of selected parameters of physical function, body composition, body mass index (BMI) and biochemical markers of metabolic health with the total testosterone (TT) levels in adult males. We aimed to analyse the correlation between these values and variations in the TT levels. METHODS: A total of 17 subjects (age = 50.2 ± 8.1 years, TT = 11.4 ± 3.8nmol/l) were included in the study. Subjects were tested on physical function (1RM on leg press, bench-press, handgrip, VO2max), body composition (DXA), biochemical parameters (morning fasting blood samples). RESULTS: TT was inversely correlated with abdominal circumference (AC) (p.