The safety and immunogenicity of a bivalent conjugate vaccine against Salmonella enterica Typhi and Paratyphi A in healthy Indian adults: a phase 1, randomised, active-controlled, double-blind trial.

BACKGROUND: Enteric fever caused by Salmonella enterica Typhi and Salmonella Paratyphi A is an important public health problem, especially in low-income and middle-income countries with limited access to safe water and sanitation. We present results from, to our knowledge, the first ever human study of a bivalent paratyphoid A-typhoid conjugate vaccine (Sii-PTCV). METHODS: In this double-blind phase 1 study, 60 healthy Indian adults were randomly assigned (1:1) to receive a single intramuscular dose of either Sii-PTCV or typhoid conjugate vaccine (Typbar-TCV). Safety was assessed by observing solicited adverse events for 1 week, unsolicited events for 1 month, and serious adverse events (SAEs) over 6 months. Immunogenicity at 1 month and 6 months was assessed by measuring anti-capsular polysaccharide antigen Vi (anti-Vi) IgG and IgA against Salmonella Typhi and anti-lipopolysaccharide (LPS) IgG against Salmonella Paratyphi A by ELISA, and functional antibodies using serum bactericidal assay (SBA) against Salmonella Paratyphi A. This study is registered with Clinical Trial Registry-India (CTRI/2022/06/043608) and is completed. FINDINGS: 60 participants were enrolled. Of these 60 participants, 57 (95%) participants were male and three (5%) participants were female. Solicited adverse events were observed in 27 (90%) of 30 participants who received Sii-PTCV and 26 (87%) of 30 participants who received Typbar-TCV. The most common local solicited event was pain in 27 (90%) participants who received Sii-PTCV and in 23 (77%) participants who received Typbar-TCV. The most common solicited systemic event was myalgia in five (17%) participants who received Sii-PTCV, whereas four (13%) participants who received Typbar-TCV had myalgia and four (13%) had headache. No vaccine-related unsolicited adverse events or SAEs were reported. The seroconversion rates on day 29 were 96·7% (95% CI 82·8-99·9) with Sii-PTCV and 100·0% (88·4-100·0) with Typbar-TCV for anti-Vi IgG; 93·3% (77·9-99·2) with Sii-PTCV and 100·0% (88·4-100·0) with Typbar-TCV for anti-Vi IgA; 100·0% (88·4-100·0) with Sii-PTCV and 3·3% (0·1-17·2) with Typbar-TCV for anti-LPS (paratyphoid); and 93·3% (77·9-99·2) with Sii-PTCV and 0% (0·0-11·6) with Typbar-TCV for SBA titres (paratyphoid). Paratyphoid anti-LPS immune responses were sustained at day 181. INTERPRETATION: Sii-PTCV was safe and immunogenic for both typhoid and paratyphoid antigens indicating its potential for providing comprehensive protection against enteric fever. FUNDING: Serum Institute of India.

Pain quality patterns in delayed onset muscle soreness of the lower back suggest sensitization of fascia rather than muscle afferents: a secondary analysis study.

Delayed onset muscle soreness (DOMS) of the lower back is considered a surrogate for acute low back pain (aLBP) in experimental studies. Of note, it is often unquestioningly assumed to be muscle pain. To date, there has not been a study analyzing lumbar DOMS in terms of its pain origin, which was the aim of this study. Sixteen healthy individuals (L-DOMS) were enrolled for the present study and matched to participants from a previous study (n = 16, L-PAIN) who had undergone selective electrical stimulation of the thoracolumbar fascia and the multifidus muscle. DOMS was induced in the lower back of the L-DOMS group using eccentric trunk extensions performed until exhaustion. On subsequent days, pain on palpation (100-mm analogue scale), pressure pain threshold (PPT), and the Pain Sensation Scale (SES) were used to examine the sensory characteristics of DOMS. Pain on palpation showed a significant increase 24 and 48 h after eccentric training, whereas PPT was not affected (p > 0.05). Factor analysis of L-DOMS and L-PAIN sensory descriptors (SES) yielded a stable three-factor solution distinguishing superficial thermal ("heat pain ") from superficial mechanical pain ("sharp pain") and "deep pain." "Heat pain " and "deep pain" in L-DOMS were almost identical to sensory descriptors from electrical stimulation of fascial tissue (L-PAIN, all p > 0.679) but significantly different from muscle pain (all p < 0.029). The differences in sensory description patterns as well as in PPT and self-reported DOMS for palpation pain scores suggest that DOMS has a fascial rather than a muscular origin.

Effects of magnesium supplementation on muscle soreness in different type of physical activities: a systematic review.

BACKGROUND: Magnesium is a micronutrient and an intracellular cation responsible for different biochemical reactions involved in energy production and storage, control of neuronal and vasomotor activity, cardiac excitability, and muscle contraction. Magnesium deficiency may result in impaired physical performance. Moreover, magnesium plays an important role on delayed onset muscle soreness after training. Thus, physically active individuals and sport specialists have to pay attention to magnesium supplementation (MgS). However, the type, timing and dosage of magnesium intake are not well elucidated yet. Hence, we aimed to systematically review the literature regarding the effects of MgS on muscle soreness in physically active individuals. We focused exclusively on MgS, excluding those studies in which magnesium was administered together with other substances. METHODS: Three electronic databases and literature sources (PUBMED, SCOPUS and Web of Sciences-Core Collection) were searched, in accordance with PRISMA guidelines. After the database search, 1254 articles were identified, and after excluding duplicates, 960 articles remained. Among these, 955 were excluded following the title and abstract screening. The remaining 5 articles were screened in full text and 4 study met the eligibility criteria. RESULTS: These studies showed that MgS reduced muscle soreness, improved performance, recovery and induced a protective effect on muscle damage. CONCLUSION: To reach these positive effects, individuals engaged in intense exercise should have a Mg requirement 10-20% higher than sedentary people, to be taken in capsules and 2 h before training. Moreover, it is suggested to maintain magnesium levels in the recommended range during the off-season. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42024501822.

Brain-derived neurotrophic factor contributes to activity-induced muscle pain in male but not female mice.

Activity-induced muscle pain increases interleukin-1ß (IL-1ß) release from muscle macrophages and the development of hyperalgesia is prevented by blockade of IL-1ß in muscle. Brain derived neurotrophic factor (BDNF) is released from sensory neurons in response to IL-1ß and mediates both inflammatory and neuropathic pain. Thus, we hypothesize that in activity-induced pain, fatigue metabolites combined with IL-1ß activate sensory neurons to increase BDNF release, peripherally in muscle and centrally in the spinal dorsal horn, to produce hyperalgesia. We tested the effect of intrathecal or intramuscular injection of BDNF-Tropomyosin receptor kinase B (TrkB) inhibitors, ANA-12 or TrkB-Fc, on development of activity-induced pain. Both inhibitors prevented the hyperalgesia when given before or 24hr after induction of the model in male but not female mice. BDNF messenger ribonucleic acid (mRNA) and protein were significantly increased in dorsal root ganglion (DRG) 24hr after induction of the model in both male and female mice. Blockade of IL-1ß in muscle had no effect on the increased BNDF mRNA observed in the activity-induced pain model, while IL-1ß applied to cultured DRG significantly induced BDNF expression, suggesting IL-1ß is sufficient but not necessary to induce BNDF. Thus, fatigue metabolites, combined with IL-1ß, upregulate BDNF in primary DRG neurons in both male and female mice, but contribute to activity-induced pain only in males.

Venlafaxine-Associated Rhabdomyolysis: A Literature Review.

PURPOSE: This systematic review aimed to investigate the clinical manifestations and characteristics of venlafaxine-associated rhabdomyolysis. METHODS: A systematic search was conducted in PubMed, Elsevier, Science Direct, Embase, Springer Link, Wiley Online Library, CNKI, and Wanfang databases from the date of database inception to January 2023. Previously reported cases of venlafaxine-associated rhabdomyolysis were identified, and relevant data from these cases were collected for descriptive statistical analysis. Cases that met the inclusion criteria were evaluated to determine the correlation between adverse reactions and venlafaxine. RESULTS: A total of 12 patients with venlafaxine-associated rhabdomyolysis were included. None of these patients had a history of muscle pain or discomfort. Of the 12 patients, 5 patients received venlafaxine at doses of ≤225 mg/d, whereas the remaining 7 patients received doses exceeding 225 mg/d. The main clinical symptoms included myalgia, muscle weakness, and renal injury. All 12 patients discontinued venlafaxine and received symptomatic care. CONCLUSIONS: Venlafaxine, used either as a monotherapy or in combination with other drugs, may be associated with rhabdomyolysis. Creatine kinase levels may normalize or significantly decrease after discontinuation of venlafaxine and symptomatic treatment.

Hyperexcitability of muscle spindle afferents in jaw-closing muscles in experimental myalgia: Evidence for large primary afferents involvement in chronic pain.

The goals of this review are to improve understanding of the aetiology of chronic muscle pain and identify new targets for treatments. Muscle pain is usually associated with trigger points in syndromes such as fibromyalgia and myofascial syndrome, and with small spots associated with spontaneous electrical activity that seems to emanate from fibers inside muscle spindles in EMG studies. These observations, added to the reports that large-diameter primary afferents, such as those innervating muscle spindles, become hyperexcitable and develop spontaneous ectopic firing in conditions leading to neuropathic pain, suggest that changes in excitability of these afferents might make an important contribution to the development of pathological pain. Here, we review evidence that the muscle spindle afferents (MSAs) of the jaw-closing muscles become hyperexcitable in a model of chronic orofacial myalgia. In these afferents, as in other large-diameter primary afferents in dorsal root ganglia, firing emerges from fast membrane potential oscillations that are supported by a persistent sodium current (INaP ) mediated by Na+ channels containing the α-subunit NaV 1.6. The current flowing through NaV 1.6 channels increases when the extracellular Ca2+ concentration decreases, and studies have shown that INaP -driven firing is increased by S100ß, an astrocytic protein that chelates Ca2+ when released in the extracellular space. We review evidence of how astrocytes, which are known to be activated in pain conditions, might, through their regulation of extracellular Ca2+ , contribute to the generation of ectopic firing in MSAs. To explain how ectopic firing in MSAs might cause pain, we review evidence supporting the hypothesis that cross-talk between proprioceptive and nociceptive pathways might occur in the periphery, within the spindle capsule.

Cell-free DNA kinetics in response to muscle-damaging exercise: A drop jump study.

A significant increase in circulating cell-free DNA (cfDNA) occurs with physical exercise, which depends on the type of exertion and the duration. The aims of this study were as follows: (1) to investigate the time course of cfDNA and conventional markers of muscle damage from immediately after to 96 h after muscle-damaging exercise; and (2) to investigate the relationship between cfDNA and indicators of primary (low-frequency fatigue and maximal voluntary isometric contraction) and secondary (creatine kinase and delayed-onset muscle soreness) muscle damage in young healthy males. Fourteen participants (age, 22 ± 2 years; weight, 84.4 ± 11.2 kg; height, 184.0 ± 7.4 cm) performed 50 intermittent drop jumps at 20 s intervals. We measured cfDNA and creatine kinase concentrations, maximal voluntary isometric contraction torque, low-frequency fatigue and delayed-onset muscle soreness before and at several time points up to 96 h after exercise. Plasma cfDNA levels increased from immediately postexercise until 72 h postexercise (P < 0.01). Elevation of postexercise cfDNA was correlated with both more pronounced low-frequency fatigue (r = -0.52, P = 3.4 × 10-11) and delayed-onset muscle soreness (r = 0.32, P = 0.00019). Levels of cfDNA change in response to severe primary and secondary muscle damage after exercise. Levels of cfDNA exhibit a stronger correlation with variables related to primary muscle damage than to secondary muscle damage, suggesting that cfDNA is a more sensitive marker of acute loss of muscle function than of secondary inflammation or damaged muscle fibres.

Anoctamin-5 related muscle disease: clinical and genetic findings in a large European cohort.

Anoctamin-5 related muscle disease is caused by biallelic pathogenic variants in the anoctamin-5 gene (ANO5) and shows variable clinical phenotypes: limb-girdle muscular dystrophy type 12 (LGMD-R12), distal muscular dystrophy type 3 (MMD3), pseudometabolic myopathy or asymptomatic hyperCKaemia. In this retrospective, observational, multicentre study we gathered a large European cohort of patients with ANO5-related muscle disease to study the clinical and genetic spectrum and genotype-phenotype correlations. We included 234 patients from 212 different families, contributed by 15 centres from 11 European countries. The largest subgroup was LGMD-R12 (52.6%), followed by pseudometabolic myopathy (20.5%), asymptomatic hyperCKaemia (13.7%) and MMD3 (13.2%). In all subgroups, there was a male predominance, except for pseudometabolic myopathy. Median age at symptom onset of all patients was 33 years (range 23-45 years). The most frequent symptoms at onset were myalgia (35.3%) and exercise intolerance (34.1%), while at last clinical evaluation most frequent symptoms and signs were proximal lower limb weakness (56.9%) and atrophy (38.1%), myalgia (45.1%) and atrophy of the medial gastrocnemius muscle (38.4%). Most patients remained ambulatory (79.4%). At last evaluation, 45.9% of patients with LGMD-R12 additionally had distal weakness in the lower limbs and 48.4% of patients with MMD3 also showed proximal lower limb weakness. Age at symptom onset did not differ significantly between males and females. However, males had a higher risk of using walking aids earlier (P = 0.035). No significant association was identified between sportive versus non-sportive lifestyle before symptom onset and age at symptom onset nor any of the motor outcomes. Cardiac and respiratory involvement that would require treatment occurred very rarely. Ninety-nine different pathogenic variants were identified in ANO5 of which 25 were novel. The most frequent variants were c.191dupA (p.Asn64Lysfs*15) (57.7%) and c.2272C>T (p.Arg758Cys) (11.1%). Patients with two loss-of function variants used walking aids at a significantly earlier age (P = 0.037). Patients homozygous for the c.2272C>T variant showed a later use of walking aids compared to patients with other variants (P = 0.043). We conclude that there was no correlation of the clinical phenotype with the specific genetic variants, and that LGMD-R12 and MMD3 predominantly affect males who have a significantly worse motor outcome. Our study provides useful information for clinical follow up of the patients and for the design of clinical trials with novel therapeutic agents.

Neurological manifestations of COVID-19 in adults and children.

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age.

Beyond the acute: pain in long COVID survivors at 1.5 years.

OBJECTIVE: Long COVID, characterized by persistent symptoms post-acute COVID-19, remains a subject of intense investigation. This study focuses on pain, a common and notable symptom reported by long COVID patients. METHOD: A cohort of 191 individuals, initially diagnosed with mild-to-moderate COVID-19, was followed up 1.5 years later to assess the frequency, clinical characteristics, and factors associated with pain persistence. RESULTS: Our study revealed that 31.9% of participants experienced at least one persistent pain symptom after 1.5 years. Headache emerged as the most prevalent symptom (29.8%), followed by myalgia (5.8%) and neuropathic pain (4.2%). Factors such as female gender and the presence of neuropathic pain symptom were identified as predictors of long-term headaches. Myalgia, showed associations with headache, arthralgia, and low ferritin levels. Persistent neuropathic pain symptom (4.2%) was linked to older age, female gender, sore throat, and headache. CONCLUSION: This study provides insights into the evolution of pain symptoms over time after COVID-19 infection, emphasizing the interconnection between different pain syndromes. This research contributes to understanding the diverse and evolving nature of pain in long COVID survivors, offering valuable insights for targeted interventions and further investigations into the underlying mechanisms of persistent pain.

Safety and efficacy of blood flow restriction exercise in individuals with neurological disorders: A systematic review.

OBJECTIVES: This systematic review evaluated the safety and efficacy of blood flow restriction exercise (BFRE) on skeletal muscle size, strength, and functional performance in individuals with neurological disorders (ND). METHODS: A literature search was performed in PubMed, CINAHL, and Embase. Two researchers independently assessed eligibility and performed data extraction and quality assessments. ELIGIBILITY CRITERIA: Study populations with ND, BFRE as intervention modality, outcome measures related to safety or efficacy. RESULTS: Out of 443 studies identified, 16 were deemed eligible for review. Three studies examined the efficacy and safety of BFRE, one study focused on efficacy results, and 12 studies investigated safety. Disease populations included spinal cord injury (SCI), inclusion body myositis (sIBM), multiple sclerosis (MS), Parkinson's disease (PD), and stroke. A moderate-to-high risk of bias was presented in the quality assessment. Five studies reported safety concerns, including acutely elevated pain and rating of perceived exertion levels, severe fatigue, muscle soreness, and cases of autonomic dysreflexia. Two RCTs reported a significant between-group difference in physical function outcomes, and two RCTs reported neuromuscular adaptations. CONCLUSION: BFRE seems to be a potentially safe and effective training modality in individuals with ND. However, the results should be interpreted cautiously due to limited quality and number of studies, small sample sizes, and a general lack of heterogeneity within and between the examined patient cohorts.

Effects of far-infrared radiation lamp therapy on recovery from a simulated soccer-match in elite female soccer players.

We investigated the effects of far-infrared radiation (FIR) lamp therapy on changes in muscle damage and performance parameters following six sets of 15-min Loughborough intermittent shuttle test (LIST), a simulated soccer match. Twenty-four elite female soccer players (20-24 y) were assigned into FIR or sham treatment group (n = 12/group). The participants received a 60-min FIR or sham treatment (30 min per muscle) over knee extensors (KE) and flexors (KF) at 2, 25, 49, 73, and 97 h post-LIST. Maximal voluntary isometric contraction (MVC) torque and muscle soreness of the KE and KF, plasma creatine kinase (CK) activity as muscle damage markers, and several performance parameters including countermovement jump (CMJ) and Yo-Yo intermittent recovery test level 1 (YYIR1) were measured before and 1, 24, 48, 72, 96, and 120 h post-LIST. Changes in the measures were compared between groups by a mixed-design two-way ANOVA. The running distance covered during LIST and changes in the measures at 1-h post-LIST (before the treatment) were similar (p = 0.118-0.371) between groups. Changes in muscle damage markers at 24-120 h post-LIST were smaller (p < 0.05, η2 = 0.208-0.467) for the FIR (e.g., MVC-KE torque decrease at 48-h post-LIST: -1 ± 2%, peak KE soreness: 16 ± 10 mm, peak CK: 172 ± 42 IU/L) than sham group (-11 ± 9%, 33 ± 7 mm, 466 ± 220 IU/L, respectively). Performance parameters recovered faster (p < 0.05, η2 = 0.142-0.308) to baseline for the FIR (e.g., decreases at 48-h post-LIST; CMJ: 0 ± 1%, YYIR1: 0 ± 1%) than sham group (-6 ± 2%, -9 ± 6%, respectively). These results suggest that the FIR lamp therapy was effective for enhancing recovery from a soccer match.

Effect of a graded running race on lower limb muscle damage, jump performance and muscle soreness in men and women.

PURPOSE: Delayed structural and functional recovery after a 20 km graded running race was analyzed with respect to the sex effect. METHODS: Thirteen female and 14 male recreational runners completed the race and three test sessions: one before (PRE) and two after, once on Day 1 or 2 (D1-2) and then on Day 3 or 4 (D3-4). Muscle damage was assessed indirectly using ultrasonography to quantify changes in cross-sectional area (CSA) of 10 lower-limb muscles. Delayed onset of muscle soreness (DOMS) was assessed for three muscle groups. Functional recovery was quantified by kinetic analysis of a squat jump (SJ) and a drop jump (DJ) test performed on a sledge ergometer. Linear mixed models were used to assess control group reproducibility and recovery patterns according to sex. RESULTS: Regardless of sex, DOMS peaked at D1-2 for all muscle groups and resolved at D3-4. CSA was increased in each muscle group until D3-4, especially in the semimembranosus muscle. A specific increase was found in the short head of the biceps femoris in women. Regardless of sex, SJ and DJ performances declined up to D3-4. Depending on the muscle, positive and/or negative correlations were found between structural and functional changes. Some of these were sex-specific. CONCLUSION: Structural and functional recovery was incomplete in both sexes up to D3-4, although DOMS had disappeared. More emphasis should be placed on hamstring muscle recovery. Highlighting the intermuscular compensations that can occur during multi-joint testing tasks, the structural-functional relationships were either positive or negative, muscle- and sex-dependent.

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.

The repeated bout effect of traditional resistance training on cycling efficiency and performance.

PURPOSE: This study examined the repeated bout effect of two resistance training bouts on cycling efficiency and performance. METHODS: Ten male resistance-untrained cyclists (age 38 ± 13 years; height 180.4 ± 7.0 cm; weight 80.1 ± 10.1; kg; VO2max 51.0 ± 7.6 ml.kg-1.min-1) undertook two resistance training bouts at six-repetition maximum. Blood creatine kinase (CK), delayed-onset of muscle soreness (DOMS), counter-movement jump (CMJ), squat jump (SJ), submaximal cycling and time-trial performance were examined prior to (Tbase), 24 (T24) and 48 (T48) h post each resistance training bout. RESULTS: There were significantly lower values for DOMS (p = 0.027) after Bout 2 than Bout 1. No differences were found between bouts for CK, CMJ, SJ and submaximal cycling performance. However, jump height (CMJ and SJ) submaximal cycling measures (ventilation and perceived exertion) were impaired at T24 and T48 compared to Tbase (p < 0.05). Net efficiency during submaximal cycling improved at Bout 2 (23.8 ± 1.2) than Bout 1 (24.3 ± 1.0%). There were no changes in cycling time-trial performance, although segmental differences in cadence were observed between bouts and time (i.e. Tbase vs T24 vs T48; p < 0.05). CONCLUSION: Cyclists improved their cycling efficiency from Bout 1 to Bout 2 possibly due to the repeated bout effect. However, cyclists maintained their cycling completion times during exercise-induced muscle damage (EIMD) in both resistance training bouts, possibly by altering their cycling strategies. Thus, cyclists should consider EIMD symptomatology after resistance training bouts, particularly for cycling-specific technical sessions, regardless of the repeated bout effect.

Downhill running increases markers of muscle damage and impairs the maximal voluntary force production as well as the late phase of the rate of voluntary force development.

PURPOSE: To examined the time-course of the early and late phase of the rate of voluntary force development (RVFD) and muscle damage markers after downhill running. METHODS: Ten recreational runners performed a 30-min downhill run at 10 km h-1 and -20% (-11.3°) on a motorized treadmill. At baseline and each day up to 4 days RVFD, knee extensors maximum voluntary isometric force (MVIC), serum creatine kinase (CK) concentration, quadriceps swelling, and soreness were assessed. The early (0-50 ms) and late (100-200 ms) phase of the RVFD, as well as the force developed at 50 and 200 ms, were also determined. RESULTS: MVIC showed moderate decrements (p < 0.05) and recovered after 4 days (p > 0.05). Force at 50 ms and the early phase were not impaired (p > 0.05). Conversely, force at 200 ms and the late phase showed moderate decrements (p < 0.05) and recovered after 3 and 4 days, respectively (p > 0.05). CK concentration, quadriceps swelling, and soreness increased (p < 0.05) were overall fully resolved after 4 days (p > 0.05). CONCLUSION: Downhill running affected the knee extensors RVFD late but not early phase. The RVFD late phase may be used as an additional marker of muscle damage in trail running.

Menthol alleviates post-race elevations in muscle soreness and metabolic and respiratory stress during running.

PURPOSE: We evaluated (1) whether participating in middle- and long-distance running races augments muscle soreness, oxygen cost, respiration, and exercise exertion during subsequent running, and (2) if post-race menthol application alleviates these responses in long-distance runners. METHODS: Eleven long-distance runners completed a 1500-m race on day 1 and a 3000-m race on day 2. On day 3 (post-race day), either a 4% menthol solution (Post-race menthol) or a placebo solution (Post-race placebo) serving as a vehicle control, was applied to their lower leg skin, and their perceptual and physiological responses were evaluated. The identical assessment with the placebo solution was also conducted without race participation (No-race placebo). RESULTS: The integrated muscle soreness index increased in the Post-race placebo compared to the No-race placebo (P < 0.001), but this response was absent in the Post-race menthol (P = 0.058). Oxygen uptake during treadmill running tended to be higher (4.3%) in the Post-race placebo vs. No-race placebo (P = 0.074). Oxygen uptake was 5.4% lower in the Post-race menthol compared to the Post-race placebo (P = 0.018). Minute ventilation during treadmill running was 6.7-7.6% higher in the Post-race placebo compared to No-race placebo, whereas it was 6.6-9.0% lower in the Post-race menthol vs. Post-race placebo (all P ≤ 0.001). The rate of perceived exertion was 7.0% lower in the Post-race menthol vs. Post-race placebo (P = 0.007). CONCLUSIONS: Middle- and long-distance races can subsequently elevate muscle soreness and induce respiratory and metabolic stress, but post-race menthol application to the lower legs can mitigate these responses and reduce exercise exertion in long-distance runners.

Impact of curcumin supplementation on exercise performance and muscle damage after a soccer match: a double-blind placebo-controlled cross-over study.

PURPOSE: Curcumin ingestion can mitigate muscle damage, soreness, and inflammation following a laboratory-based eccentric exercise. Similar effects were observed in recent field-based studies wherein responses were evaluated after a soccer match. However, various potential confounding factors, such as matching opponent skill levels and daily training conditions, may have influenced the outcomes. In the present study, we investigated whether curcumin intake ameliorates changes in muscle damage markers following a soccer match while controlling for the potential confounding factors. METHODS: Fifteen collegiate athletes were tested in a randomized, double-blind, cross-over manner. They were recruited from the same college soccer team and thus followed the same daily training regimen and competition levels. Furthermore, athletes positioning during matches were counterbalanced. They consumed either 180 mg/day of curcumin or a placebo starting 1 h before the match and continuing for 2 days after a match (two 45-min plays and a 15-min half-time). Muscle soreness, jump performance (including countermovement jump and rebound jump index), and inflammatory and muscle damage markers (high-sensitive C-reactive protein, serum creatine kinase activity, and urinary N-terminal fragment of titin concentration) were evaluated before and after the match. The washout period between matches was set at 1 week. RESULTS: After the match, all markers showed similarity between the placebo and curcumin conditions (all P > 0.208). CONCLUSION: These findings indicate that ingesting 180 mg/day of curcumin may not expedite recovery from muscle damage elicited by soccer matches in collegiate soccer players.

Statins increase muscle pain or weakness at 1 y, with an absolute excess of 11 events/1000 person-y.

SOURCE CITATION: Cholesterol Treatment Trialists' Collaboration. Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials. Lancet. 2022;400:832-45. 36049498.

Innovations in the Assessment of Skeletal Muscle Health: A Glimpse into the Future.

Skeletal muscle is the largest organ system in the human body and plays critical roles in athletic performance, mobility, and disease pathogenesis. Despite growing recognition of its importance by major health organizations, significant knowledge gaps remain regarding skeletal muscle health and its crosstalk with nearly every physiological system. Relevant public health challenges like pain, injury, obesity, and sarcopenia underscore the need to accurately assess skeletal muscle health and function. Feasible, non-invasive techniques that reliably evaluate metrics including muscle pain, dynamic structure, contractility, circulatory function, body composition, and emerging biomarkers are imperative to unraveling the complexities of skeletal muscle. Our concise review highlights innovative or overlooked approaches for comprehensively assessing skeletal muscle in vivo. We summarize recent advances in leveraging dynamic ultrasound imaging, muscle echogenicity, tensiomyography, blood flow restriction protocols, molecular techniques, body composition, and pain assessments to gain novel insight into muscle physiology from cellular to whole-body perspectives. Continued development of precise, non-invasive tools to investigate skeletal muscle are critical in informing impactful discoveries in exercise and rehabilitation science.