A 2-hydroxybutyrate-mediated feedback loop regulates muscular fatigue.

Several metabolites have been shown to have independent and at times unexpected biological effects outside of their metabolic pathways. These include succinate, lactate, fumarate, and 2-hydroxyglutarate. 2-Hydroxybutyrate (2HB) is a byproduct of endogenous cysteine synthesis, produced during periods of cellular stress. 2HB rises acutely after exercise; it also rises during infection and is also chronically increased in a number of metabolic disorders. We show here that 2HB inhibits branched-chain aminotransferase enzymes, which in turn triggers a SIRT4-dependent shift in the compartmental abundance of protein ADP-ribosylation. The 2HB-induced decrease in nuclear protein ADP-ribosylation leads to a C/EBPß-mediated transcriptional response in the branched-chain amino acid degradation pathway. This response to 2HB exposure leads to an improved oxidative capacity in vitro. We found that repeated injection with 2HB can replicate the improvement to oxidative capacity that occurs following exercise training. Together, we show that 2-HB regulates fundamental aspects of skeletal muscle metabolism.

Comparing The Effects of Compression Contrast Therapy and Dry Needling on Muscle Functionality, Pressure Pain Threshold, and Perfusion after Isometric Fatigue in Forearm Muscles of Combat Sports Athletes: A Single-Blind Randomized Controlled Trial.

The aim of this study was to compare the acute effects of compression contrast therapy (CT) and dry needling therapy (DN) on muscle tension (MT), muscle strength (Fmax), pressure pain threshold (PPT), and perfusion (PU) following fatigue of forearm muscles (e.g., flexor carpi radialis) in combat sports athletes. A single-blind randomized controlled trial was employed. Participants first underwent muscle fatigue induction, which involved sustaining an isometric handgrip at 60% of their maximum voluntary contraction in 5-second cycles. This was followed by exposure to one of the regenerative therapies. Forty-five participants were randomly assigned to one of three groups: CT/DN (n = 15), CT/ShDN (n = 15), and ShCT/DN (n = 15). The sham condition (Sh) involved a simulated version of the technique. Measurements were taken at four time points: (i) at rest; (ii) immediately after exercise that led to a state of fatigue; (iii) 5 minutes after therapy (PostTh5min); and (iv) 24 hours after therapy (PostTh24h). Each participant was exposed to one experimental condition and one control condition, thereby undergoing evaluation in two sessions. Significant differences between groups were found in MT during the PostTh5min (p = 0.005), as well as in PU during the PostTh5min (p < 0.001) and PU during the PostTh24h (p < 0.001). All groups showed significant improvements at 5 minutes post-therapy compared to immediately post-muscle fatigue. As conclusions, CT/DN seems to be significantly better for enhancing MT and PU after 5 minutes of muscle fatigue induction. Using either CT, DN, or both combined is recommended to enhance the recovery of muscle functionality and properties, favoring recovery and potentially speeding up performance enhancement.

6'-Sialyllactose Alleviates Muscle Fatigue through Reduced Blood Lactate Level after Treadmill Exercise in Mice.

6'-Sialyllactose (6'-SL), found in human breast milk, exhibits anti-inflammatory, immune function-enhancing, brain development-promoting, and gut health-improving effects. However, its effects on muscle fatigue remain unknown. Here, we aimed to investigate the effects of 6'-SL on blood lactate level, muscle fiber type, and oxidative phosphorylation protein complexes (OXPHOS) in muscle after exercise using C57BL/6J male mice. C57BL/6J mice were randomly assigned to control or 100 mg/kg 6'-SL. After 12 weeks of 6'-SL administration, the mice were made to perform treadmill exercise; their blood lactate and glucose levels were measured at the basal level (rest) and 0, 5, and 10 min after treadmill exercise. Results showed that 6'-SL treatment in C57BL/6J mice significantly reduced blood lactate level and improved blood glucose level. Moreover, 6'-SL increased the expression of slow-myosin heavy chain (MHC) and OXPHOS in gastrocnemius muscle. In addition, 6'-SL treatment for 12 weeks did not affect food intake, serum biomarkers of tissue injury, and lipid profiles compared with those of the controls. These findings indicate that non-toxic 6'-SL suppressed muscle fatigue during exercise by promoting protein expression of muscle fibers, especially slow-twitch muscle fibers characterized by abundant OXPHOS complexes and decreased blood lactate level. This study suggests that 6'-SL holds promise as a nutritional supplement in exercise and clinical settings, subject to further validation.

Phycocyanin attenuates skeletal muscle damage and fatigue via modulation of Nrf2 and IRS-1/AKT/mTOR pathway in exercise-induced oxidative stress in rats.

Prolonged strenuous exercise induces oxidative stress, leading to oxidative damage, skeletal muscle fatigue, and reduced exercise performance. The body compensates for oxidative stress through antioxidant actions, while related enzymes alone may not overcome excessive oxidative stress during prolonged strenuous exercise. Phycocyanin is an important antioxidant supplement derived from blue-green algae, which may be helpful in this type of situation. This study determined the effects of phycocyanin on exercise performance from prolonged strenuous exercise. Forty Sprague Dawley male rats were divided into 5 groups (n = 8 /group); Control group (C), Exercise group (E), and Exercise with supplement groups receiving low dose (Phycocyanin = 100 mg/kg BW; ELP) and high dose (Phycocyanin = 200 mg/kg BW; EHP) or vitamin C (Vitamin C = 200 mg/kg BW; VC). Phycocyanin was found to decrease oxidative damage markers, muscle fatigue, and muscle atrophy through the activated AKT/mTOR pathway. This was also found to have greater increases in antioxidants via Nrf2 signaling and increases ATP synthesis, GLUT4 transporters, and insulin signaling due to increased IRS-1/AKT signaling. In conclusion, phycocyanin was found to reduce oxidative damage and muscle atrophy, including an increase in insulin signaling in skeletal muscles leading to increased exercise performance in rats.

The deflection of fatigued neck.

The human neck is a unique mechanical structure, highly flexible but fatigue prone. The rising prevalence of neck pain and chronic injuries has been attributed to increasing exposure to fatigue loading in activities such as prolonged sedentary work and overuse of electronic devices. However, a causal relationship between fatigue and musculoskeletal mechanical changes remains elusive. This work aimed to establish this relationship through a unique experiment design, inspired by a cantilever beam mechanical model of the neck, and an orchestrated deployment of advanced motion-force measurement technologies including dynamic stereo-radiographic imaging. As a group of 24 subjects performed sustained-till-exhaustion neck exertions in varied positions-neutral, extended, and flexed, their cervical spine musculoskeletal responses were measured. Data verified the occurrence of fatigue and revealed fatigue-induced neck deflection which increased cervical lordosis or kyphosis by 4-5° to 11°, depending on the neck position. This finding and its interpretations render a renewed understanding of muscle fatigue from a more unified motor control perspective as well as profound implications on neck pain and injury prevention.

Influence of an inspiratory muscle fatigue protocol on healthy youths on respiratory muscle strength, vertical jump performance and muscle oxygen saturation: a randomized controlled trial.

BACKGROUND: Inspiratory muscle fatigue has been shown to have effects on limbs blood flow and physical performance. This study aimed to evaluate the influence of an inspiratory muscle fatigue protocol on respiratory muscle strength, vertical jump performance and muscle oxygen saturation in healthy youths. METHODS: A randomized and double-blinded controlled clinical trial, was conducted. Twenty-four participants aged 18-45 years, non-smokers and engaged in sports activity at least three times a week for a minimum of one year were enrolled in this investigation. Participants were randomly assigned to three groups: Inspiratory Muscle Fatigue (IMFG), Activation, and Control. Measurements of vertical jump, diaphragmatic ultrasound, muscle oxygen saturation, and maximum inspiratory pressure were taken at two stages: before the intervention (T1) and immediately after treatment (T2). RESULTS: The IMFG showed lower scores in muscle oxygen saturation and cardiorespiratory variables after undergoing the diaphragmatic fatigue intervention compared to the activation and control groups (p < 0.05). For the vertical jump variables, intragroup differences were found (p < 0.01), but no differences were shown between the three groups (p > 0.05). CONCLUSIONS: Inspiratory muscle fatigue appears to negatively impact vertical jump performance, muscle oxygen saturation and inspiratory muscle strength in healthy youths. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT06271876. Date of registration 02/21/2024. https://clinicaltrials.gov/study/NCT06271876 .

The validity and reliability of quadriceps twitch force as a measure of skeletal muscle fatigue while cycling.

The measurement of skeletal muscle fatigue in response to cycling exercise is commonly done in isometric conditions, potentially limiting its ecological validity, and creating challenges in monitoring the time course of muscle fatigue across an exercise bout. This study aimed to determine if muscle fatigue could be reliably assessed by measuring quadriceps twitch force evoked while pedaling, using instrumented pedals. Nine participants completed three laboratory visits: a step incremental test to determine power output at lactate threshold, and on separate occasions, two constant-intensity bouts at a power output 10% above lactate threshold. Femoral nerve electrical stimulation was applied to elicit quadriceps twitch force both while pedaling (dynamic) and at rest (isometric). The test-retest reliability of the dynamic twitch forces and the agreement between the dynamic and isometric twitch forces were evaluated. Dynamic twitch force was found to have excellent reliability in an unfatigued state (intraclass correlation coefficient (ICC) = 0.920 and mean coefficient of variation (CV) = 7.5%), and maintained good reliability at task failure (ICC = 0.846 and mean CV = 11.5%). When comparing dynamic to isometric twitch forces across the task, there was a greater relative decline in the dynamic condition (P = 0.001). However, when data were normalized to the 5 min timepoint when potentiation between conditions was presumed to be more similar, this difference disappeared (P = 0.207). The reliability of this method was shown to be commensurate with the gold standard method utilizing seated isometric dynamometers and offers a new avenue to monitor the kinetics of muscle fatigue during cycling in real time.

The effects of fatigue on the relationship between ankle angle at initial contact and the knee and hip joints in landing: Assessing the risk of ACL injury.

BACKGROUND: Anterior cruciate ligament (ACL) injuries may correlate with lower limb angles and biomechanical factors in both dominant and non-dominant legs at initial contact (IC) post-landing. This study aims to investigate the correlation between ankle angles in three axes at IC and knee and hip joint angles during post-spike landings in professional volleyball players, both pre- and post-fatigue induction. RESEARCH QUESTION: To what extent does fatigue influence lower limb joint angles, and what is the relationship between ankle joint angles and hip and knee angles at IC during the landing phase following a volleyball spike? METHODS: Under conditions involving the peripheral fatiguing protocol, the lower limb joint angles at IC following post-spike landings were measured in 28 professional male volleyball players aged between 19 and 28 years, who executed the Bosco fatigue protocol both before and after inducing fatigue. A paired t-test was utilized to compare the joint angles pre- and post-fatigue in both dominant and non-dominant legs. Furthermore, Pearson's correlation test was conducted to explore the relationship between ankle angles at IC and the corresponding knee and hip joint angles. RESULTS: The findings of the study revealed that fatigue significantly increased hip external rotation and decreased knee joint flexion and external rotation in both the dominant and non-dominant legs (p < 0.05). Additionally, correlation analysis demonstrated that the ankle joint's positioning in the frontal and horizontal planes was significantly associated with hip flexion and external rotation at the IC, as well as with knee flexion and rotation (0.40 < r < 0.80). CONCLUSION: Fatigue increased hip external rotation and ankle internal rotation, weakening the correlation between these joints while strengthening the ankle-knee relationship, indicating a reduced hip control in jumps. This suggests a heightened ACL injury risk in the dominant leg due to the weakened ankle-hip connection, contrasting with the non-dominant leg.

Sustained submaximal isometric wrist flexion and wrist extension contractions uniquely impair maximal voluntary contraction force in the antagonist wrist action.

When fatigued, the wrist extensors, which are the primary wrist stabilizers, impair distal upper limb motor performance in a surprisingly similar way as when fatiguing the wrist flexors. It is possible that the wrist extensors are so active as antagonists that they develop an equal degree of fatigue during wrist flexion contractions, making it difficult to truly isolate their impact on performance. Thus, the purpose of this study was to examine how wrist flexion/extension forces are impaired following either agonist or antagonist sustained submaximal wrist contractions. 13 male participants attended four laboratory sessions. In these sessions, fatigue was induced via a sustained submaximal isometric contraction of either wrist flexion or extension. These contractions were held for up to 10 min at 20% of the participant's baseline maximal voluntary contraction (MVC) force. Throughout the sustained contraction, intermittent agonist (matching the sustained contraction) or antagonist (opposing the sustained contraction) MVCs were performed. Unsurprisingly, agonist MVC forces decreased significantly more than antagonist (Agonist: 58.5%, Antagonist: 86.5% of MVC, P < 0.001). However, while there were no differences in antagonist wrist extension and flexion MVC decreases (Wrist Flexion: 87.5%, Wrist Extension: 85.5%, P = 0.41), wrist extension MVCs did decrease significantly more than wrist flexion MVCs when forces were expressed relative to the agonist (P = 0.036). These findings partially support the hypothesis that the wrist extensors may be more susceptible to developing fatigue when functioning as antagonists than the wrist flexors. This work will help equip future research into the motor control of the upper limb and the prevention of forearm-related musculoskeletal disorders.

Head-neck cooling effects on central and peripheral fatigue, motor accuracy, and blood markers of stress in men with multiple sclerosis and healthy men: A randomized crossover study.

BACKGROUND: The present study aimed to investigate whether head and neck cooling (at 18 °C next to the skin) and fatiguing submaximal exercise at a thermoneutral ambient temperature can induce peripheral and central responses in healthy men and those with multiple sclerosis (MS). METHODS: A local head-neck cooling (at 18 °C next to the skin) intervention in men with a relapsing-remitting form of MS (n = 18; age 30.9 ± 8.1 years) and healthy men (n = 22; age 26.7 ± 5.9 years) was assessed. Men in both groups performed 100 intermittent isometric knee extensions with 5 s contractions and 20 s of rest. The primary variables were measured before exercise, after 50 and 100 repetitions, and 1 h after recovery. The central activation ratio, maximal voluntary contraction, electrically induced force, electromyography, contractile properties, blood markers, muscle temperature, and perception of effort were measured. RESULTS: Compared with noncooled conditions, head and neck cooling increased the central capacity to activate exercising muscles but resulted in greater exercise-induced peripheral fatigue in men with MS (p < 0.05). Local cooling did not affect motor accuracy or the amplitude of electromyography signals; however, these factors were related to the intensity of the motor task (p > 0.05). The changes in central and peripheral fatigability induced by local cooling during submaximal exercise were more pronounced in men with MS than in healthy men (p < 0.05). CONCLUSION: Head and neck cooling enhances central activation of muscles during exercise, leading to improved exercise performance compared with noncooled conditions in men with MS.

Variability in musculoskeletal fatigue responses associated with repeated exposure to an occupational overhead drilling task completed on successive days.

Emerging research suggests that muscular and kinematic responses to overhead work display a high degree of variability in fatigue-related muscular and kinematics changes, both between and within individuals when evaluated across separate days. This study examined whether electromyographic (EMG), kinematic, and kinetic responses to an overhead drilling task performed until volitional fatigue were comparable to those of a repeated identical exposure of the task completed 1 week later. Surface EMG and intramuscular EMG, sampled from 7 shoulder muscles, and right upper limb kinematics and kinetics were analyzed from 15 male and 14 female participants. No significant day-to-day changes in EMG mean power frequency (MPF) were observed, though serratus anterior displayed significantly less fatigue-related increase in EMG root-mean-squared (RMS) signal amplitude on day 2. Unfatigued upper kinematics on day 2 featured an increase in thoracohumeral elevation, elbow flexion, and decrease in wrist ulnar deviation compared to unfatigued state on day 1. Fatigue-related changes in shoulder joint flexion moment that were present on day 1 were reduced on day 2, suggesting that a more efficient overhead work strategy was learned and preserved across successive days. Day-to-day changes in upper limb joint angle variability, quantified by median absolute deviation (MdAD), were joint dependent. Despite yielding a variable fatigue-related kinetic strategy on both days, kinematic and kinetic fatigue-related changes on a second day of completing an overhead drilling task suggested a potential kinematic learning effect.

Activation of skeletal muscle mechanoreceptors and nociceptors reduces the exercise performance of the contralateral homologous muscles.

Increasing evidence suggests that activation of muscle nerve afferents may inhibit central motor drive, affecting contractile performance of remote exercising muscles. Although these effects are well documented for metaboreceptors, very little is known about the activation of mechano- and mechanonociceptive afferents on performance fatigability. Therefore, the purpose of the present study was to examine the influence of mechanoreceptors and nociceptors on performance fatigability. Eight healthy young males undertook four randomized experimental sessions on separate occasions in which the experimental knee extensors were the following: 1) resting (CTRL), 2) passively stretched (ST), 3) resting with delayed onset muscle soreness (DOMS), or 4) passively stretched with DOMS (DOMS+ST), whereas the contralateral leg performed an isometric time to task failure (TTF). Changes in maximal voluntary contraction (ΔMVC), potentiated twitch force (ΔQtw,pot), and voluntary muscle activation (ΔVA) were also assessed. TTF was reduced in DOMS+ST (-43%) and ST (-29%) compared with CTRL. DOMS+ST also showed a greater reduction of VA (-25% vs. -8%, respectively) and MVC compared with CTRL (-28% vs. -45%, respectively). Rate of perceived exertion (RPE) was significantly increased at the initial stages (20-40-60%) of the TTF in DOMS+ST compared with all conditions. These findings indicate that activation of mechanosensitive and mechanonociceptive afferents of a muscle with DOMS reduces TTF of the contralateral homologous exercising limb, in part, by reducing VA, thereby accelerating mechanisms of central fatigue.NEW & NOTEWORTHY We found that activation of mechanosensitive and nociceptive nerve afferents of a rested muscle group experiencing delayed onset muscle soreness was associated with reduced exercise performance of the homologous exercising muscles of the contralateral limb. This occurred with lower muscle voluntary activation of the exercising muscle at the point of task failure.

Effects of unilateral and bilateral lower extremity fatigue on static stance and postural adjustments response to the externally initiated perturbation.

The study investigated the effects of unilateral and bilateral lower extremity fatigue on both postural stability and postural adjustments. Fourteen young male subjects performed unilateral and bilateral dynamic lower extremity pedaling exercises with 5 sets of 20 times at 50 % maximum voluntary contraction. Center of pressure (COP) signals were recorded before and after the fatigue exercise. Electromyography activities of six trunk and leg muscles were recorded and analyzed during the anticipatory (APAs) and compensatory (CPAs) postural adjustments. The results showed that both fatiguing exercises caused an increase in COP and larger APAs and CPAs in the rectus femoris and tibialis anterior during externally initiated perturbation. However, the observed indicators showed no clear difference between unilateral and bilateral fatigue. These results validated that when enlarged APAs were not sufficient to resist the external perturbation, the central nervous system increased the strength of CPAs to maintain the stability of the body. These findings provided a perspective on the association between APAs and CPAs, which may apply to the athletic training or rehabilitation on postural control.

Neuromuscular fatigue and cognitive constraints independently modify lower extremity landing biomechanics in healthy and chronic ankle instability individuals.

The purpose was to determine the impact of both cognitive constraint and neuromuscular fatigue on landing biomechanics in healthy and chronic ankle instability (CAI) participants. Twenty-three male volunteers (13 Control and 10 CAI) performed a single-leg landing task before and immediately after a fatiguing exercise with and without cognitive constraints. Ground Reaction Force (GRF) and Time to Stabilization (TTS) were determined at landing in vertical, anteroposterior (ap) and mediolateral (ml) axes using a force plate. Three-dimensional movements of the hip, knee and ankle were recorded during landing using a motion capture system. Exercise-induced fatigue decreased ankle plantar flexion and inversion and increased knee flexion. Neuromuscular fatigue decreased vertical GRF and increased ml GRF and ap TTS. Cognitive constraint decreased ankle internal rotation and increased knee and hip flexion during the flight phase of landing. Cognitive constraint increased ml GRF and TTS in all three axes. No interaction between factors (group, fatigue, cognitive) were observed. Fatigue and cognitive constraint induced greater knee and hip flexion, revealing higher proximal control during landing. Ankle kinematic suggests a protective strategy in response to fatigue and cognitive constraints. Finally, these two constraints impair dynamic stability that could increase the risk of ankle sprain.

Analysis and study on biomarkers of local muscle fatigue caused by repetitive lifting task.

BACKGROUND: Work-related musculoskeletal disorders (WMSDs) show a rapid growth trend. It has brought a huge economic burden to the society and become a serious occupational health problem that needs to be solved urgently. This study aimed to analyze the local muscle response under continuous ergonomic load, screen sensitive fatigue-related biomarkers and provide data support for the early prevention of local muscle damage and the exploration of early warning indicators. METHODS: Thirteen male college student volunteers were recruited to perform simulated repetitive manual lifting tasks in the laboratory. The lifting task was designed for 4 periods which lasted for 12 min in each, and then paused for 3 min for sampling. Local muscle fatigue is assesed by the Rating of perceived exertion (RPE) and the Joint analysis of sEMG spectrum and amplitude (JASA). Elbow venous blood was collected and 14 kinds of biomarkers were analyzed, which included Metabolic markers Ammonia (AMM), Lactic acid (LAC), Creatine kinase (CK), Lactate dehydrogenase (LDH), Cartilage oligomeric matrix protein (COMP), C-telopeptide of collagen I and II (CTX-I, CTX-II) and Calcium ion (Ca2+); Oxidative stress marker Glutathione (GSH); Inflammatory markers C-reaction protein (CRP), Prostaglandin E2 (PG-E2), Interleukin-6 (IL-6) and Tumor necrosis factor α (TNF-α); Pain marker Neuropeptide Y (NPY). Repeated measures analysis of variance (Repeated ANOVA), linear regression analysis, t-test and spearman correlation analysis were used to analyze the data. RESULTS: Both subjective and objective fatigue appeared at the same period. Serum AMM, LAC, CK, LDH, COMP, CTX-II, Ca2+ and NPY after fatigue were significantly higher than those before fatigue (p < 0.05). There was a certain degree of correlation between the markers with statistical differences before and after fatigue. CONCLUSIONS: Metabolic markers (serum AMM, LAC, CK, LDH, COMP, CTX-II, Ca2+) and pain markers (serum NPY) can reflect local muscle fatigue to a certain extent in repetitive manual lifting tasks. It is necessary to further expand the research on fatigue-related biomarkers in different types of subjects and jobs in the future.

Effect of fatigue on knee biomechanics during the sidestep cutting manoeuvre: A modelling approach.

Loading both lateral and medial compartments is crucial to understanding the effect of muscle fatigue during sidestep cutting. The present study investigated the changes in tibiofemoral contact forces in the medial and lateral compartments and the muscle force contributions during the sidestep-cutting manoeuvre after a handball-specific fatigue protocol. Twenty female handball athletes performed three trials of the sidestep-cutting manoeuvre before (baseline) and after the fatigue protocol. Motion capture and ground reaction forces were measured, and the data were processed in OpenSim. The variables were compared using statistical parametric mapping (SPM), with a significance level of p < 0.05. The results showed a decreased knee flexion angle during fatigue in the early stance phase. In addition, the post-fatigue analysis demonstrated significantly reduced forces in vasti muscles. Similarly, during fatigue, the SPM analysis showed decreased tibiofemoral contact forces in the vertical and anterior directions. Vertical force applied to both medial and lateral condyles demonstrated a significant reduction after the fatigue protocol. These results indicated that forces applied to the tibiofemoral joint were reduced following the fatigue protocol compared to the baseline values. However, no consistent evidence exists that fatigue increases the risk of knee injuries.

Digital Sensing Systems for Electromyography.

Surface electromyogram (EMG) signals find diverse applications in movement rehabilitation and human-computer interfacing. For instance, future advanced prostheses, which use artificial intelligence, will require EMG signals recorded from several sites on the forearm. This requirement will entail complex wiring and data handling. We present the design and evaluation of a bespoke EMG sensing system that addresses the above challenges, enables distributed signal processing, and balances local versus global power consumption. Additionally, the proposed EMG system enables the recording and simultaneous analysis of skin-sensor impedance, needed to ensure signal fidelity. We evaluated the proposed sensing system in three experiments, namely, monitoring muscle fatigue, real-time skin-sensor impedance measurement, and control of a myoelectric computer interface. The proposed system offers comparable signal acquisition characteristics to that achieved by a clinically-approved product. It will serve and integrate future myoelectric technology better via enabling distributed machine learning and improving the signal transmission efficiency.

Insight into motor fatigue mechanisms in natalizumab treated multiple sclerosis patients with wearing off.

Motor fatigue in Multiple Sclerosis (MS) is due to reduced motor cortex (M1) output and altered sensorimotor network (SMN) modulation. Natalizumab, a disease-modifying therapy, reduces neuroinflammation and improves fatigue. However, some patients treated with natalizumab experience fatigue recurrence ('wearing-off') before subsequent infusions. Wearing-off provides a valuable window into MS-related motor fatigue mechanisms in a controlled, clinically stable, setting. This study investigates whether wearing-off is associated with worsening motor fatigue and its neurophysiological mechanisms and assesses natalizumab's effect on MS-related fatigue. Forty-five relapsing-remitting MS patients with wearing-off symptoms were evaluated pre- and post-natalizumab infusion. Assessments included evaluating disability levels, depressive symptoms, and the impact of fatigue symptoms on cognitive, physical, and psychosocial functioning. The motor fatigue index was computed through the number of blocks completed during a fatiguing task and peripheral, central, and supraspinal fatigue (M1 output) were evaluated by measuring the superimposed twitches evoked by peripheral nerve and transcranial magnetic stimulation of M1. Transcranial magnetic stimulation-electroencephalography assessed M1 effective connectivity by measuring TMS-evoked potentials (TEPs) within the SMN before- and after the task. We found that wearing-off was associated with increased motor fatigue index, increased central and supraspinal fatigue, and diminished task-related modulation of TEPs compared to post-natalizumab infusion. Wearing-off was also associated with worsened fatigue impact and depression symptom scores. We conclude that the wearing-off phenomenon is associated with worsening motor fatigue due to altered M1 output and modulation of the SMN. Motor fatigue in MS may reflect reversible, inflammation-related changes in the SMN that natalizumab can modulate. Our findings apply primarily to MS patients receiving natalizumab, emphasizing the need for further research on other treatments with wearing-off.

The effect of individualised post-exercise blood flow restriction on recovery following strenuous resistance exercise: A randomised controlled trial.

The purpose was to clarify the effect of individualised post-exercise blood flow restriction (PE-BFR) on measures of recovery following strenuous resistance exercise. Twenty resistance-trained adults were randomised to a PE-BFR or control (CON) group and completed a fatigue protocol of five sets of 10 repetitions of maximal intensity concentric and eccentric seated knee extension exercise. Participants then lied supine with cuffs applied to the upper thigh and intermittently inflated to 80% limb occlusion pressure (PE-BFR) or 20 mmHg (CON) for 30 min (3 × 5 min per leg). Peak torque (PT), time-to-peak torque (TTP), countermovement jump height (CMJ), muscle soreness (DOMS) and perceived recovery (PR) were measured pre-fatigue, immediately post-fatigue and at 1, 24, 48 and 72 h post-fatigue. Using a linear mixed-effect model, PE-BFR was found to have greater recovery of CMJ at 48 h (mean difference [MD]=-2.8, 95% confidence interval [CI] -5.1, 0.5, p = 0.019), lower DOMS at 48 (MD = 3.0, 95% CI 1.2, 4.9, p = 0.001) and 72 h (MD = 1.95, 95% CI -1.2, 1.5, p = 0.038) and higher PR scores at 24 (MD = -1.7, 95% CI -3.4, -0.1, p = 0.038), 48 (MD = -3.1, 95% CI -4.8, -1.5, p < 0.001) and 72 h (MD = -2.2, 95% CI -3.8, -0.5, p = 0.011). These findings suggest that individualised PE-BFR accelerates recovery after strenuous exercise.

Effect of rest duration between sets on fatigue and recovery after short intense plyometric exercise.

Plyometric training is characterized by high-intensity exercise which is performed in short term efforts divided into sets. The purpose of the present study was twofold: first, to investigate the effects of three distinct plyometric exercise protocols, each with varying work-to-rest ratios, on muscle fatigue and recovery using an incline-plane training machine; and second, to assess the relationship between changes in lower limb muscle strength and power and the biochemical response to the three exercise variants employed. Forty-five adult males were randomly divided into 3 groups (n = 15) performing an exercise of 60 rebounds on an incline-plane training machine. The G0 group performed continuous exercise, while the G45 and G90 groups completed 4 sets of 15 repetitions, each set lasting 45 s with 45 s rest in G45 (work-to-rest ratio of 1:1) and 90 s rest in G90 (1:2 ratio). Changes in muscle torques of knee extensors and flexors, as well as blood lactate (LA) and ammonia levels, were assessed before and every 5 min for 30 min after completing the workout. The results showed significantly higher (p < 0.001) average power across all jumps generated during intermittent compared to continuous exercise. The greatest decrease in knee extensor strength immediately post-exercise was recorded in group G0 and the least in G90. The post-exercise time course of LA changes followed a similar pattern in all groups, while the longer the interval between sets, the faster LA returned to baseline. Intermittent exercise had a more favourable effect on muscle energy metabolism and recovery than continuous exercise, and the work-to-rest ratio of 1:2 in plyometric exercises was sufficient rest time to allow the continuation of exercise in subsequent sets at similar intensity.