Changes in nerve growth factor in vastus lateralis muscle after the first versus second bout of one-leg eccentric cycling.

Delayed onset muscle soreness (DOMS) develops after performing unaccustomed eccentric exercises. Animal studies have shown that DOMS is mechanical hyperalgesia through nociceptor sensitization induced by nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) upregulated by cyclooxygenase-2 (COX-2). However, no previous study has investigated these in relation to DOMS in humans. This study compared the first and second bouts of one-leg eccentric cycling (ECC) for changes in NGF, GDNF, and COX-2 mRNA in the vastus lateralis (VL). Seven healthy adults (18-40 years) performed two bouts of ECC (10 sets of 50 contractions) with 80% maximal voluntary concentric peak torque separated by 2 weeks (ECC1, ECC2). Muscle soreness that was assessed by a visual analog scale and maximal voluntary isometric contraction (MVC) torque of the knee extensors were measured before, immediately after (MVC only), 24 and 48 h post-exercise. Muscle biopsy was taken from the VL before the first bout from nonexercised leg (control) and 24 h after each bout from the exercised leg, and analyzed for NGF, GDNF, and COX-2 mRNA. Peak DOMS was more than two times greater and MVC torque at 48 h post-exercise was approximately 20% smaller after ECC1 than ECC2 (p < 0.05), suggesting the repeated bout effect. NGF mRNA level was higher (p < 0.05) post-ECC1 (0.79 ± 0.68 arbitrary unit) than control (0.06 ± 0.07) and post-ECC2 (0.08 ± 0.10). GDNF and COX-2 mRNA did not show significant differences between control, post-ECC1, and post-ECC2. These results suggest that an increase in NGF is associated with the development of DOMS in humans.

Exercise builds the scaffold of life: muscle extracellular matrix biomarker responses to physical activity, inactivity, and aging.

Skeletal muscle extracellular matrix (ECM) is critical for muscle force production and the regulation of important physiological processes during growth, regeneration, and remodelling. ECM remodelling is a tightly orchestrated process, sensitive to multi-directional tensile and compressive stresses and damaging stimuli, and its assessment can convey important information on rehabilitation effectiveness, injury, and disease. Despite its profound importance, ECM biomarkers are underused in studies examining the effects of exercise, disuse, or aging on muscle function, growth, and structure. This review examines patterns of short- and long-term changes in the synthesis and concentrations of ECM markers in biofluids and tissues, which may be useful for describing the time course of ECM remodelling following physical activity and disuse. Forces imposed on the ECM during physical activity critically affect cell signalling while disuse causes non-optimal adaptations, including connective tissue proliferation. The goal of this review is to inform researchers, and rehabilitation, medical, and exercise practitioners better about the role of ECM biomarkers in research and clinical environments to accelerate the development of targeted physical activity treatments, improve ECM status assessment, and enhance function in aging, injury, and disease.

The effects of home-based exercise therapy for breast cancer-related fatigue induced by radical radiotherapy.

BACKGROUND: Radiotherapy (RT) can lead to cancer-related fatigue (CRF) and decreased health-related quality of life (HRQoL) in breast cancer patients. The purpose of this trial was to examine the feasibility and efficacy of a home-based resistance and aerobic exercise intervention for reducing CRF and improving HRQoL in breast cancer patients during RT. METHODS: Women with breast cancer (N = 106) commencing RT were randomized to 12 weeks of home-based resistance and aerobic exercise (EX) or usual care/control (CON). The primary endpoint was CRF, with secondary endpoints of HRQoL, sleep duration and quality, and physical activity. Measurements were undertaken prior to RT, at completion of RT (~ 6 weeks), at completion of the intervention (12 weeks), and 6 and 12 months after RT completion, while CRF was also measured weekly during RT. RESULTS: Eighty-nine women completed the study (EX = 43, CON = 46). Over the 12-week intervention, EX completed 1-2 resistance training sessions and accumulated 30-40 min of aerobic exercise weekly. For CRF, EX had a quicker recovery both during and post-RT compared to CON (p < 0.05). Moreover, there was a significant difference in HRQoL between groups at RT completion, with HRQoL unchanged in CON and higher in EX (p < 0.05). There was no change in sleep duration or quality for either group and there were no exercise-related adverse effects. CONCLUSIONS: Home-based resistance and aerobic exercise during RT is safe, feasible, and effective in accelerating CRF recovery and improving HRQoL. Improvements in CRF and HRQoL for these patients can be achieved with smaller exercise dosages than stated in the generic recommendations for breast cancer.

Elastic tubes: the ideal equipment for telehealth exercise medicine in the management of prostate cancer?

Prostate cancer (PCa) affects 1 in 8 men, but exercise therapy has been shown to be a very effective intervention not only to induce physiological benefits but to also reduce the side effects of cancer treatments typically administered during PCa. The COVID19 pandemic has restricted access to exercise clinics, a problem which always existed for people living in rural and remote areas. This caused many exercise physiologists and researchers to transition their clinic-based exercise to online, home-based exercise. We would like to propose that researchers and exercise physiologists should consider the use of elastic tubes in both research and the clinical management of PCa, when exercise programs are administered remotely, as their characteristics make them an ideal exercise equipment. In this article, the characteristics, considerations, and information on quantifying exercise dosage when using elastic tubes in remote exercise delivery are discussed.

Exercise medicine for cancer cachexia: targeted exercise to counteract mechanisms and treatment side effects.

PURPOSE: Cancer-induced muscle wasting (i.e., cancer cachexia, CC) is a common and devastating syndrome that results in the death of more than 1 in 5 patients. Although primarily a result of elevated inflammation, there are multiple mechanisms that complement and amplify one another. Research on the use of exercise to manage CC is still limited, while exercise for CC management has been recently discouraged. Moreover, there is a lack of understanding that exercise is not a single medicine, but mode, type, dosage, and timing (exercise prescription) have distinct health outcomes. The purpose of this review was to examine the effects of these modes and subtypes to identify the most optimal form and dosage of exercise therapy specific to each underlying mechanism of CC. METHODS: The relevant literatures from MEDLINE and Scopus databases were examined. RESULTS: Exercise can counteract the most prominent mechanisms and signs of CC including muscle wasting, increased protein turnover, systemic inflammation, reduced appetite and anorexia, increased energy expenditure and fat wasting, insulin resistance, metabolic dysregulation, gut dysbiosis, hypogonadism, impaired oxidative capacity, mitochondrial dysfunction, and cancer treatments side-effects. There are different modes of exercise, and each mode has different sub-types that induce vastly diverse changes when performed over multiple sessions. Choosing suboptimal exercise modes, types, or dosages can be counterproductive and could further contribute to the mechanisms of CC without impacting muscle growth. CONCLUSION: Available evidence shows that patients with CC can safely undertake higher-intensity resistance exercise programs, and benefit from increases in body mass and muscle mass.

Increases in Integrin-ILK-RICTOR-Akt Proteins, Muscle Mass, and Strength after Eccentric Cycling Training.

PURPOSE: Recently, it has been suggested that a cellular pathway composed of integrin, integrin-linked kinase (ILK), rapamycin-insensitive companion of mTOR (RICTOR), and Akt may facilitate long-term structural and functional adaptations associated with exercise, independent of the mTORC1 pathway. Therefore, we examined changes in integrin-ILK-RICTOR-Akt protein in vastus lateralis (VL) before and after 8 wk of eccentric cycling training (ECC), which was expected to increase muscle function and VL cross-sectional area (CSA). METHODS: Eleven men (23 ± 4 yr) completed 24 sessions of ECC with progressive increases in intensity and duration, resulting in a twofold increase in work from the first three (75.4 ± 14.1 kJ) to the last three sessions (150.7 ± 28.4 kJ). Outcome measures included lower limb lean mass, VL CSA, static strength, and peak and average cycling power output. These measures and VL samples were taken before and 4-5 d after the last training session. RESULTS: Significant (P < 0.05) increases in integrin-ß1 (1.64-fold) and RICTOR (2.99-fold) protein as well as the phosphorylated-to-total ILK ratio (1.70-fold) were found, but integrin-α7 and Akt did not change. Increases in lower limb, thigh, and trunk lean mass (2.8%-5.3%, P < 0.05) and CSA (13.3% ± 9.0%, P < 0.001) were observed. Static strength (18.1% ± 10.8%) and both peak (8.6% ± 10.5%) and average power output (7.4% ± 8.3%) also increased (P < 0.05). However, no significant correlations were found between the magnitude of increases in protein and the magnitude of increases in CSA, static strength, or power output. CONCLUSIONS: In addition to increased muscle mass, strength, and power, we demonstrate that ECC increases integrin-ß1 and RICTOR total protein and p-ILK/t-ILK, which may play a role in protection against muscle damage as well as anabolic signaling to induce muscle adaptations.

Radiotherapy before or during androgen-deprivation therapy does not blunt the exercise-induced body composition protective effects in prostate cancer patients: A secondary analysis of two randomized controlled trials.

BACKGROUND: Androgen deprivation therapy (ADT) contributes to lean mass loss and adiposity increases in prostate cancer patients. Radiotherapy during ADT might act synergistically and further worsen body composition. Previous investigations have shown that resistance training is an effective method of preserving body composition during ADT, however, most have not accounted for direct or indirect effects of other therapies, such as radiotherapy. Therefore, the purpose of this study was to examine training adaptations of the tissue composition in patients receiving radiation therapy (RT) prior or during ADT. METHODS: Analyses were performed by combining data from two previous trials for a total of 131 prostate cancer patients who underwent a combination of resistance and aerobic exercise training (N = 70, age: 68.9 ± 6.6y, RT-before: 13%, RT-during: 14%) or usual care (N = 61, age: 67.5 ± 7.9y, RT-before: 16%, RT-during: 20%) for 3 months upon ADT onset. Whole-body lean mass (LM), fat percentage and appendicular LM were determined by dual energy x-ray absorptiometry, and lower-leg muscle area and density by peripheral computed tomography at baseline (onset of ADT) and at 3 months post-intervention. Covariates included RT prior and during the intervention, demographic characteristics, physical symptoms, and chronic conditions. RESULTS: Radiotherapy before or during the intervention did not affect body composition. Only the usual care group experienced a significant decrease in whole-body LM (-994 ± 150 g, P < 0.001) and appendicular LM (-126 ± 19 g, P < 0.001), and an increase in whole-body fat percentage (1% ± 0.1%, P < 0.001). There was no change in lower-leg muscle area or density in either group. CONCLUSION: We suggest that radiation prior to and during ADT does not interfere with the beneficial effects of exercise training on body composition in men with prostate cancer.

Changes in plasma hydroxyproline and plasma cell-free DNA concentrations after higher- versus lower-intensity eccentric cycling.

PURPOSE: We examined changes in plasma creatine kinase (CK) activity, hydroxyproline and cell-free DNA (cfDNA) concentrations in relation to changes in maximum voluntary isometric contraction (MVIC) torque and delayed-onset muscle soreness (DOMS) following a session of volume-matched higher- (HI) versus lower-intensity (LI) eccentric cycling exercise. METHODS: Healthy young men performed either 5 × 1-min HI at 20% of peak power output (n = 11) or 5 × 4-min LI eccentric cycling at 5% of peak power output (n = 9). Changes in knee extensor MVIC torque, DOMS, plasma CK activity, and hydroxyproline and cfDNA concentrations before, immediately after, and 24-72 h post-exercise were compared between groups. RESULTS: Plasma CK activity increased post-exercise (141 ± 73.5%) and MVIC torque decreased from immediately (13.3 ± 7.8%) to 48 h (6.7 ± 13.5%) post-exercise (P < 0.05), without significant differences between groups. DOMS was greater after HI (peak: 4.5 ± 3.0 on a 10-point scale) than LI (1.2 ± 1.0). Hydroxyproline concentration increased 40-53% at 24-72 h after both LI and HI (P < 0.05). cfDNA concentration increased immediately after HI only (2.3 ± 0.9-fold, P < 0.001), with a significant difference between groups (P = 0.002). Lack of detectable methylated HOXD4 indicated that the cfDNA was not derived from skeletal muscle. No significant correlations were evident between the magnitude of change in the measures, but the cfDNA increase immediately post-exercise was correlated with the maximal change in heart rate during exercise (r = 0.513, P = 0.025). CONCLUSION: Changes in plasma hydroxyproline and cfDNA concentrations were not associated with muscle fiber damage, but the increased hydroxyproline in both groups suggests increased collagen turnover. cfDNA may be a useful metabolic-intensity exercise marker.

Comparison between high- and low-intensity eccentric cycling of equal mechanical work for muscle damage and the repeated bout effect.

PURPOSE: We compared high- and low-intensity eccentric cycling (ECC) with the same mechanical work for changes in muscle function and muscle soreness, and examined the changes after subsequent high-intensity ECC. METHODS: Twenty men performed either high-intensity ECC (1 min × 5 at 20% of peak power output: PPO) for two bouts separated by 2 weeks (H-H, n = 11), or low-intensity (4 min × 5 at 5% PPO) for the first and high-intensity ECC for the second bout (L-H, n = 9). Changes in indirect muscle damage markers were compared between groups and bouts. RESULTS: At 24 h after the first bout, both groups showed similar decreases in maximal isometric (70° knee angle, - 10.6 ± 11.8%) and isokinetic ( - 11.0 ± 8.2%) contraction torque of the knee extensors (KE), squat ( - 7.7 ± 10.4%) and counter-movement jump ( - 5.9 ± 8.4%) heights (p < 0.05). Changes in KE torque and jump height were smaller after the second than the first bout for both the groups (p < 0.05). Increases in plasma creatine kinase activity were small, and no significant changes in vastus lateralis or intermedius thickness nor ultrasound echo-intensity were observed. KE soreness with palpation was greater (p < 0.01) in H-H (peak: 4.2 ± 1.0) than L-H (1.4 ± 0.6) after the first bout, but greater in L-H (3.6 ± 0.9) than H-H (1.5 ± 0.5) after the second bout. This was also found for muscle soreness with squat, KE stretch and gluteal palpation. CONCLUSION: The high- and low-intensity ECC with matched mechanical work induced similar decreases in muscle function, but DOMS was greater after high-intensity ECC, which may be due to greater extracellular matrix damage and inflammation.

The Influence of Heat Acclimation and Hypohydration on Post-Weight-Loss Exercise Performance.

PURPOSE: To examine the influence of fluid intake on heat acclimation and the subsequent effects on exercise performance following acute hypohydration. METHODS: Participants were randomly assigned to 1 of 2 groups, either able to consume water ad libitum (n = 10; age 23 [3] y, height 1.81 [0.09] m, body mass 87 [13] kg; HAW) or not allowed fluid (n = 10; age 26 [5] y, height 1.76 [0.05] m, body mass 79 [10] kg; HANW) throughout 12 × 1.5-h passive heat-acclimation sessions. Experimental trials were completed on 2 occasions before (2 baseline trials) and 1 following the heat-acclimation sessions. These sessions involved 3 h of passive heating (45°C, 38% relative humidity) to induce hypohydration followed by 3 h of ad libitum food and fluid intake after which participants performed a repeat sled-push test to assess physical performance. Urine and blood samples were collected before, immediately, and 3 h following hypohydration to assess hydration status. Mood was also assessed at the same time points. RESULTS: No meaningful differences in physiological or performance variables were observed between HANW and HAW at any time point. Using pooled data, mean sprint speed was significantly (P < .001) faster following heat acclimation (4.6 [0.7] s compared with 5.1 [0.8] s). Furthermore, heat acclimation appeared to improve mood following hypohydration. CONCLUSIONS: Results suggest that passive heat-acclimation protocols may be effective at improving short-duration repeat-effort performance following acute hypohydration.

Pathological mechanisms and therapeutic outlooks for arthrofibrosis.

Arthrofibrosis is a fibrotic joint disorder that begins with an inflammatory reaction to insults such as injury, surgery and infection. Excessive extracellular matrix and adhesions contract pouches, bursae and tendons, cause pain and prevent a normal range of joint motion, with devastating consequences for patient quality of life. Arthrofibrosis affects people of all ages, with published rates varying. The risk factors and best management strategies are largely unknown due to a poor understanding of the pathology and lack of diagnostic biomarkers. However, current research into the pathogenesis of fibrosis in organs now informs the understanding of arthrofibrosis. The process begins when stress signals stimulate immune cells. The resulting cascade of cytokines and mediators drives fibroblasts to differentiate into myofibroblasts, which secrete fibrillar collagens and transforming growth factor-ß (TGF-ß). Positive feedback networks then dysregulate processes that normally terminate healing processes. We propose two subtypes of arthrofibrosis occur: active arthrofibrosis and residual arthrofibrosis. In the latter the fibrogenic processes have resolved but the joint remains stiff. The best therapeutic approach for each subtype may differ significantly. Treatment typically involves surgery, however, a pharmacological approach to correct dysregulated cell signalling could be more effective. Recent research shows that myofibroblasts are capable of reversing differentiation, and understanding the mechanisms of pathogenesis and resolution will be essential for the development of cell-based treatments. Therapies with significant promise are currently available, with more in development, including those that inhibit TGF-ß signalling and epigenetic modifications. This review focuses on pathogenesis of sterile arthrofibrosis and therapeutic treatments.

Iron status markers are only transiently affected by a football game.

We examined the temporal variation of iron's status markers during a 60 h period following a football game. Thirty-four male football players were randomly assigned to a control group (CG, N = 14, participated only in measurements and training) or an experimental group (EG, N = 20, took part in a football game one week after the completion of the competitive season). All participants trained regularly for two consecutive days after the game. Training and game load was monitored with high time-resolution global positioning system (GPS) devices. Blood samples were collected and muscle damage markers and repeated sprint ability (RSA) were assessed pre-game and at 2 h, 12 h 36 h and 60 h post-game. No changes were noted in CG. Iron concentration decreased (P < 0.05) 2 h post-game and normalised thereafter whereas total iron binding capacity increased (P < 0.05) 12-60 h of recovery (P < 0.05). Erythrocytes, haemoglobin (HGB) concentration, plasma volume, haematocrit, mean cell volume, mean cell HGB, mean cell HGB concentration, red cell width-SD, red cell width-CV, ferritin concentration and transferrin saturation remained unaltered during the intervention period. Creatine kinase activity and muscle soreness increased (P < 0.05) throughout recovery in EG. RSA declined (P < 0.05) until 36 h of recovery and normalised thereafter. Our data demonstrate that iron status markers are only transiently affected by a football game.