Gait kinematics differ by bout duration and setting.

BACKGROUND: Gait kinematics differ between settings and among young and older adults with and without knee osteoarthritis. Out-of-lab data has a variety of walking bout characteristics compared to controlled in-lab settings. The effect of walking bout duration on gait analysis results is unclear, and there is no standardized procedure for segmenting or selecting out-of-lab data for analysis. RESEARCH QUESTION: Do gait kinematics differ by bout duration or setting in young and older adults with and without knee osteoarthritis? METHODS: Ten young (28.1±3.5 yrs), ten older adults (60.8±3.3 yrs), and ten older adults with knee osteoarthritis (64.1±3.6 yrs) performed a standard in-lab gait analysis followed by a prescribed walking route outside the lab at a comfortable speed with four IMUs. Walking speed, stride length, and sagittal hip, knee, and ankle angular excursion (ROM) were calculated for each identified stride. Out-of-lab strides included straight-line, level walking divided into strides that occurred during long (>60 s) or short (≤60 s) bouts. Gait kinematics were compared between in-lab and both out-of-lab bout durations among groups. RESULTS: Significant main effects of setting or duration were found for walking speed and stride length, but there were no significant differences in hip, knee, or ankle joint ROM. Walking speed and stride length were greater in-lab followed by long and short bout out-of-lab. No significant interaction was observed between group and setting or bout duration for any spatiotemporal variables or joint ROMs. SIGNIFICANCE: Out-of-lab gait data can be beneficial in identifying gait characteristics that individuals may not encounter in the traditional lab setting. Setting has an impact on walking kinematics, so comparisons of in-lab and free-living gait may be impacted by the duration of walking bouts. A standardized approach for to analyzing out-of-lab gait data is important for comparing studies and populations.

Revisiting the concept of bout: associations of moderate-to-vigorous physical activity sessions and non-sessions with mortality.

INTRODUCTION: Current physical activity guidelines recommend 150 min of moderate-to-vigorous physical activity (MVPA) for health benefits, regardless of the pattern of MVPA. However, MVPA that occurs in sessions (MVPA-S) may have different health implications compared to MVPA that is not accumulated in sessions (MVPA-nonS). This study aimed to investigate the associations of MVPA-S and MVPA-nonS with mortality. METHODS: We conducted a cohort study of the National Health and Nutrition Examination Survey 2003-2006 (n = 5,658) with accelerometer-measured physical activity at baseline and mortality followed through December 31, 2019. A session was defined as a time window of 30 min or longer where the average intensity was at or above 2020 counts/minute. MVPA accumulated within such sessions was quantified as MVPA-S, while MVPA accumulated outside the sessions was quantified as MVPA-nonS. We examined the joint association of MVPA-S and MVPA-nonS by classifying the participants into four groups (both < 75 min/week [referent], MVPA-S ≥ 75 and MVPA-nonS < 75, MVPA-S < 75 and MVPA-nonS ≥ 75, and both ≥ 75). We used 75 min as the cut-point because it is half of the guideline-recommended MVPA volume where a strong MVPA-mortality association has been observed in previous studies, and because it was close to the median of MVPA-nonS (75 min/week was the 54th percentile), allowing a sufficient sample size in each group for testing statistical significance. The hazard ratios and 95% confidence intervals were estimated with adjustment for important confounders. RESULTS: During 13.9 years of follow-up (74,988 person-years), there were 1,424 deaths, out of which 472 were related to cardiovascular diseases (CVD). Compared to the referent combination (both < 75), the hazard ratios in the other three combinations were 0.48 (0.33-0.69), 0.85 (0.71-1.01), and 0.45 (0.30-0.67) for all-cause mortality; and were 0.34 (0.17-0.70), 0.96 (0.69-1.33), and 0.40 (0.17-0.90) for CVD mortality, respectively. Results were largely consistent in the spline-based models, age- and sex-stratified analyses, complete-case analysis, competing risk analysis, and the analysis excluding deaths within two years of follow-up. CONCLUSION: In conclusion, MVPA accumulated in sessions that lasted at least 30 min was associated with significant reductions in all-cause and CVD-specific mortality risks. The health implications of MVPA that were not accumulated in such sessions warrant further investigation.

Moderate intensity intermittent lifestyle physical activity is associated with better executive function in older adults.

Executive functions are among the first cognitive abilities to decline with age and age-related executive function slowing predisposes older adults to cognitive disorders and disease. Intermittent Lifestyle Physical Activity (ILPA) reflects brief, unplanned activity that occurs during routine daily activities and is operationalized as activity bouts <60s. Our understanding of short bouts of habitual physical activity and executive functions is limited. We tested the hypothesis that greater amounts of ILPA in moderate and vigorous intensity domains would be associated with better executive function in older adults. Forty older adults (26 females, 68 ± 6, >55 years; body mass index: 26.6 ± 4.3 kg/m2) completed a Trail-Making-Task and wore an activPAL 24-hr/day for 6.2 ± 1.8-days. For each intensity, total time and time spent in bouts <60 s were determined. Trail A (processing speed) and Trail B (cognitive flexibility) were completed in 25.8 ± 8.2 s and 63.2 ± 26.2 s, respectively. Non-parametric Spearman's rank correlations report that moderate ILPA (3.2 ± 3.2 min/day) and total-moderate physical activity (20.1 ± 16.0 min/day) were associated with faster Trail A (total-moderate physical activity: ρ=-0.48; moderate-ILPA: ρ = -0.50; both, p < 0.003) and Trail B time (total-moderate physical activity: ρ = 0.36; moderate-ILPA: ρ = -0.46; both, p < 0.020). However, the results show no evidence of an association with either vigorous physical activity or light physical activity (total time or ILPA bouts: all, p > 0.180). Moderate physical activity accumulated in longer bouts (>60 s) was not associated with Trail B time (p = 0.201). Therefore, more total moderate physical activity and shorter bouts (<60 s) may result in better executive functions in older adults.

Acute physical exercise prevents memory amnesia caused by protein synthesis inhibition in rats' hippocampus.

The benefits of physical exercise (PE) on memory consolidation have been well-documented in both healthy and memory-impaired animals. However, the underlying mechanisms through which PE exerts these effects are still unclear. In this study, we aimed to investigate the role of hippocampal protein synthesis in memory modulation by acute PE in rats. After novel object recognition (NOR) training, rats were subjected to a 30-min moderate-intensity acute PE on the treadmill, while control animals did not undergo any procedures. Using anisomycin (ANI) and rapamycin (RAPA), compounds that inhibit protein synthesis through different mechanisms, we manipulated protein synthesis in the CA1 region of the hippocampus to examine its contribution to memory consolidation. Memory was assessed on days 1, 7, and 14 post-training. Our results showed that inhibiting protein synthesis by ANI or RAPA impaired NOR memory consolidation in control animals. However, acute PE prevented this impairment without affecting memory persistence. We also evaluated brain-derived neurotrophic factor (BDNF) levels after acute PE at 0.5h, 2h, and 12h afterward and found no differences in levels compared to animals that did not engage in acute PE or were only habituated to the treadmill. Therefore, our findings suggest that acute PE could serve as a non-pharmacological intervention to enhance memory consolidation and prevent memory loss in conditions associated with hippocampal protein synthesis inhibition. This mechanism appears not to depend on BDNF synthesis in the early hours after exercise.

Reduction in systemic muscle stress markers after exercise-induced muscle damage following concurrent training and supplementation with specific collagen peptides - a randomized controlled trial.

Introduction: Collagen peptide supplementation in conjunction with exercise has been shown to improve structural and functional adaptations of both muscles and the extracellular matrix. This study aimed to explore whether specific collagen peptide (SCP) supplementation combined with a concurrent training intervention can improve muscular stress after exercise-induced muscle damage, verified by reliable blood markers. Methods: 55 sedentary to moderately active males participating in a concurrent training (CT) intervention (3x/week) for 12 weeks were administered either 15 g of SCP or placebo (PLA) daily. Before (T1) and after the intervention (T2), 150 muscle-damaging drop jumps were performed. Blood samples were collected to measure creatine kinase (CK), lactate dehydrogenase (LDH), myoglobin (MYO) and high-sensitivity C-reactive protein (hsCRP) before, after, and at 2 h, 24 h and 48 h post exercise. Results: A combination of concurrent training and SCP administration showed statistically significant interaction effects, implying a lower increase in the area under the curve (AUC) of MYO (p = 0.004, ηp2 = 0.184), CK (p = 0.01, ηp2 = 0.145) and LDH (p = 0.016, ηp2 = 0.133) in the SCP group. On closer examination, the absolute mean differences (ΔAUCs) showed statistical significance in MYO (p = 0.017, d = 0.771), CK (p = 0.039, d = 0.633) and LDH (p = 0.016, d = 0.764) by SCP supplementation. Conclusion: In conclusion, 12 weeks of 15 g SCP supplementation combined with CT intervention reduced acute markers of exercise-induced muscle damage and improved post-exercise regenerative capacity, as evidenced by the altered post-exercise time course. The current findings indicate that SCP supplementation had a positive effect on the early phase of muscular recovery by either improving the structural integrity of the muscle and extracellular matrix during the training period or by accelerating membrane and cytoskeletal protein repair. Clinical trial registration: https://www.clinicaltrials.gov/study/NCT05220371?cond=NCT05220371&rank=1, NCT05220371.

Reduced plasma calcitonin gene-related peptide level identified in cluster headache: A prospective and controlled study.

BACKGROUND: The role of calcitonin gene-related peptide (CGRP) in the cyclic pattern of cluster headache is unclear. To acquire biological insight and to comprehend why only episodic cluster headache responds to CGRP monoclonal antibodies, we examined whether plasma CGRP changes between disease states (i.e. bout, remission and chronic) and controls. METHODS: The present study is a prospective case-control study. Participants with episodic cluster headache were sampled twice (bout and remission). Participants with chronic cluster headache and controls were sampled once. CGRP concentrations were measured in plasma with a validated radioimmunoassay. RESULTS: Plasma was collected from 201 participants diagnosed with cluster headache according to the International Classification of Headache Disorders, 3rd edition, and from 100 age- and sex-matched controls. Overall, plasma CGRP levels were significantly lower in participants with cluster headache compared to controls (p < 0.05). In episodic cluster headache, CGRP levels were higher in bout than in remission (mean difference: 17.1 pmol/L, 95% confidence interval = 9.8-24.3, p < 0.0001). CGRP levels in bout were not different from chronic cluster headache (p = 0.266). CONCLUSIONS: Plasma CGRP is unsuitable as a diagnostic biomarker of cluster headache or its disease states. The identified reduced CGRP levels suggest that CGRPs role in cluster headache is highly complex and future investigations are needed into the modulation of CGRP and its receptors.

Fractional amplitude of low-frequency fluctuations associated with µ-opioid and dopamine receptor distributions in the central nervous system after high-intensity exercise bouts.

Introduction: Dopaminergic, opiod and endocannabinoid neurotransmission are thought to play an important role in the neurobiology of acute exercise and, in particular, in mediating positive affective responses and reward processes. Recent evidence indicates that changes in fractional amplitude of low-frequency fluctuations (zfALFF) in resting-state functional MRI (rs-fMRI) may reflect changes in specific neurotransmitter systems as tested by means of spatial correlation analyses. Methods: Here, we investigated this relationship at different exercise intensities in twenty young healthy trained athletes performing low-intensity (LIIE), high-intensity (HIIE) interval exercises, and a control condition on three separate days. Positive And Negative Affect Schedule (PANAS) scores and rs-fMRI were acquired before and after each of the three experimental conditions. Respective zfALFF changes were analyzed using repeated measures ANOVAs. We examined the spatial correspondence of changes in zfALFF before and after training with the available neurotransmitter maps across all voxels and additionally, hypothesis-driven, for neurotransmitter maps implicated in the neurobiology of exercise (dopaminergic, opiodic and endocannabinoid) in specific brain networks associated with "reward" and "emotion." Results: Elevated PANAS Positive Affect was observed after LIIE and HIIE but not after the control condition. HIIE compared to the control condition resulted in differential zfALFF decreases in precuneus, temporo-occipital, midcingulate and frontal regions, thalamus, and cerebellum, whereas differential zfALFF increases were identified in hypothalamus, pituitary, and periaqueductal gray. The spatial alteration patterns in zfALFF during HIIE were positively associated with dopaminergic and µ-opioidergic receptor distributions within the 'reward' network. Discussion: These findings provide new insight into the neurobiology of exercise supporting the importance of reward-related neurotransmission at least during high-intensity physical activity.

Adherence to the WHO recommendation of three weekly days of vigorous intensity activities in children: an accelerometry study of vigorous physical activity bouts.

Background: The World Health Organization (WHO) recommends that children and adolescents incorporate vigorous intensity activities (VIAs) at least three days a week. This recommendation has not been sufficiently studied using objective methods, such as accelerometry. Physical education classes and extracurricular sports activities are optimal opportunities for compliance with this recommendation. Objective: To identify VIAs through bouts of vigorous physical activity (VPA-Bouts) evaluated with accelerometry and, with this, to know the compliance with the recommendation on VIAs. Methods: A cross-sectional study of the habitual physical activity of 353 children (8-9 years old) was carried out using accelerometry and participation in organized extracurricular sports activities was asked through a questionnaire. School days with and without physical education class, weekends, and the average weekly day were identified, as well as school time and out-of-school time. A VPA-Bout was defined as an interval of at least 60 minutes with a proportion of VPA of at least 16.7% in boys and 12.5% in girls (10.0 and 7.5 minutes/hour of VPA, respectively). Results: The average daily time in organized extracurricular sports activities declared by questionnaire and the average daily duration of the VPA-Bouts evaluated with accelerometers in the extracurricular period was 21.3 (SD 19.8) and 23.9 (SD 31.2) minutes, respectively, in boys, whereas, in girls it was 20.2 (SD 17.4) and 11.0 (SD 16.9) minutes, respectively. In school time including a physical education class, there was a higher proportion of VPA-Bouts than without these classes (with: 28.6%, without: 2.1%, p < 0.001). Children who reported at least three weekly hours of organized extracurricular sports activities accumulated a higher proportion of school afternoons with VPA-Bouts than those with fewer weekly hours of this type of activities (≥3 hours/week: 27.5%, <3 hours/week: 9.3%, p < 0.001). On the weekend, boys who reported at least three weekly hours of organized extracurricular sports activities performed more VPA-Bouts than those participating in less weekly hours, while in girls no significant differences were observed (weekend; boys, ≥3 hours/week: 26.0%, <3 hours/week: 9.0%, p < 0.001; girls: 8.3%, 8.0%, p = 0.917). Compliance with the recommendation to incorporate VIAs at least three days a week was 23.8%. Children who reported at least three weekly hours of extracurricular sports activities achieved higher compliance than those who reported fewer extracurricular activities (≥3 hours/week: 35.1%, <3 hours/week: 12.7%, p < 0.001). Additionally, boys showed higher compliance rates than girls (boys: 32.9%, girls: 15.3%, p < 0.001). Conclusion: One in every four children met the WHO recommendation to incorporate VIAs at least three days a week, as evaluated by accelerometry. Physical education classes and extracurricular organized sports activities contributed to compliance with this recommendation.

Effects of single and repeated bouts of flywheel exercise on jump performance and muscle damage in athletes and non athletes.

BACKGROUND: Although recent studies have investigated the effects of flywheel (FW) training on muscle function, the effects of transient FW exercise on jump performance in athletes are unknown. This study examined the effects of single and repeated bouts of FW squat exercises on jump performance and muscle damage in male collegiate basketball players. METHODS: The participants were 10 healthy college-age men (nonathletes) and 11 male basketball players (athletes). The intervention involved 100 squat exercises (10 repetitions × 10 sets) using an FW device. To examine the repeated-bout effects, the protocol was conducted again after a 2-week interval. Squat jumps, countermovement jumps, drop jumps, and rebound jumps were evaluated as jump performance, while isometric maximal voluntary contraction (MVC) torque in knee extension, muscle soreness, range of motion, thigh circumference, muscle thickness, and echo intensity were evaluated as markers of muscle damage. Measurements were taken at baseline, immediately after exercise, 24 h later, and 72 h later. RESULTS: The jump performance of nonathletes decreased after exercise (p < 0.05), while that of the athletes did not. The results were similar for muscle soreness. MVC torque decreased significantly after the first exercise in both groups (p < 0.05) and was significantly lower in the nonathletes versus athletes. Significant repeated-bout effects were found for muscle soreness in nonathletes but not athletes. CONCLUSIONS: These results suggest that a single bout of FW exercise reduces jump performance in male nonathletes but not basketball players.

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.

Delayed onset muscle soreness and exercise-induced skeletal muscle memory / 中国组织工程研究

BACKGROUND:Unaccustomed exercise triggers skeletal muscle damage,but produces a specific training effect that reduces muscle re-injury to reduce pain-muscle memory. OBJECTIVE:Based on the etiology of delayed onset muscle soreness,to review the existence and possible mechanism of skeletal muscle memory in delayed onset muscle soreness and to present new insights into the prevention and treatment of delayed onset muscle soreness. METHODS:The first author searched in PubMed,Embase,Web of Science,CNKI and WanFang databases for relevant literature published from January 1990 to December 2022.The keywords were"DOMS,skeletal muscle memory,exercise skeletal muscle adaptation,repeat turn effect,exercise and autophagy,autophagy and inflammation"in English and Chinese,respectively.A total of 102 articles were finally included for review. RESULTS AND CONCLUSION:The etiology of delayed onset muscle soreness is currently believed to be an acute inflammatory response due to metabolic disorders,mechanical injury and oxidative stress,while exercise-induced skeletal muscle memory can reduce delayed onset muscle soreness and exercise re-injury.When the duration,frequency and intensity of centrifugal training are gradually increased,symptoms of the injury can be minimized or even avoided.Therefore,based on the mechanism of exercise-induced skeletal muscle memory,it is the future research direction to find more effective ways to prevent and alleviate exercise-induced muscle injury.This review aims to(1)clarify the existence of exercise-induced skeletal muscle memory;(2)explore the possible mechanisms of exercise-induced skeletal muscle memory and propose the relationship between this memory and skeletal muscle autophagy;and(3)provide new strategies for the prevention and treatment of delayed onset muscle soreness by improving the level of skeletal muscle autophagy.

The temporal structure of goal-directed and habitual operant behavior.

Operant behavior can reflect the influence of goal-directed and habitual processes. These can be distinguished by changes to response rate following devaluation of the reinforcing outcome. Whether a response is goal directed or habitual depends on whether devaluation affects response rate. Response rate can be decomposed into frequencies of bouts and pauses by analyzing the distribution of interresponse times. This study sought to characterize goal-directed and habitual behaviors in terms of bout-initiation rate, within-bout response rate, bout length, and bout duration. Data were taken from three published studies that compared sensitivity to devaluation following brief and extended training with variable-interval schedules. Analyses focused on goal-directed and habitual responding, a comparison of a habitual response to a similarly trained response that had been converted back to goal-directed status after a surprising event, and a demonstration of contextual control of habit and goal direction in the same subjects. Across experiments and despite responses being clearly distinguished as goal directed and habitual by total response rate, analyses of bout-initiation rate, within-bout rate, bout length, and bout duration did not reveal a pattern that distinguished goal-directed from habitual responding.

Influence of specific collagen peptides and 12-week concurrent training on recovery-related biomechanical characteristics following exercise-induced muscle damage-A randomized controlled trial.

Introduction: It has been shown that short-term ingestion of collagen peptides improves markers related to muscular recovery following exercise-induced muscle damage. The objective of the present study was to investigate whether and to what extent a longer-term specific collagen peptide (SCP) supplementation combined with a training intervention influences recovery markers following eccentric exercise-induced muscle damage. Methods: Fifty-five predominantly sedentary male participants were assigned to consume either 15 g SCP or placebo (PLA) and engage in a concurrent training (CT) intervention (30 min each of resistance and endurance training, 3x/week) for 12 weeks. Before (T1) and after the intervention (T2), eccentric muscle damage was induced by 150 drop jumps. Measurements of maximum voluntary contraction (MVC), rate of force development (RFD), peak RFD, countermovement jump height (CMJ), and muscle soreness (MS) were determined pre-exercise, immediately after exercise, and 24 and 48 h post-exercise. In addition, body composition, including fat mass (FM), fat-free mass (FFM), body cell mass (BCM) and extracellular mass (ECM) were determined at rest both before and after the 12-week intervention period. Results: Three-way mixed ANOVA showed significant interaction effects in favor of the SCP group. MVC (p = 0.02, ηp2 = 0.11), RFD (p < 0.01, ηp2 = 0.18), peak RFD (p < 0.01, ηp2 = 0.15), and CMJ height (p = 0.046, ηp2 = 0.06) recovered significantly faster in the SCP group. No effects were found for muscle soreness (p = 0.66) and body composition (FM: p = 0.41, FFM: p = 0.56, BCM: p = 0.79, ECM: p = 0.58). Conclusion: In summary, the results show that combining specific collagen peptide supplementation (SCP) and concurrent training (CT) over a 12-week period significantly improved markers reflecting recovery, specifically in maximal, explosive, and reactive strength. It is hypothesized that prolonged intake of collagen peptides may support muscular adaptations by facilitating remodeling of the extracellular matrix. This, in turn, could enhance the generation of explosive force. Clinical trial registration: ClinicalTrials.gov, identifier ID: NCT05220371.

Effects of a single bout of mobile action video game play on attentional networks.

Background: Video game play has been linked to a range of cognitive advantages, and investigations in this domain have predominantly utilized cross-sectional designs or long-term training paradigms. Nevertheless, the specific effects of engaging in a single bout of video game play remain poorly understood. Consequently, the objective of this study is to examine the influence of a single session of mobile action video game (MAVG) play on attentional networks among college students. Methods: Seventy-two nonvideo game players were assigned randomly into an MAVG and a control game group. Participants in the MAVG group engaged in a 60-minute session of an action video game played on mobile phones, while the control group played a mobile card game for the same duration. All participants completed the attentional network test (ANT), which assesses alerting, orienting, and executive control network efficiencies, before and after the intervention. Results: The MAVG group had significantly improved alerting network efficiency following the intervention, compared to before (p < 0.05); the control game group did not. Neither executive control network efficiency nor orienting network efficiency were found to be improved by the intervention. Conclusion: The present data demonstrated that a single bout of MAVG play can improve alerting network efficiency selectively in young-adult college students. MAVGs may be useful for promoting attentional function with the advantages of being accessible virtually any time and anywhere.

Imiquimod-induced pruritus in female wild-type and knockin Wistar rats: underscoring behavioral scratching in a rat model for antipruritic treatments.

OBJECTIVES: Animal models of skin disease are used to evaluate therapeutics to alleviate disease. One common clinical dermatological complaint is pruritus (itch), but there is a lack of standardization in the characterization of pre-clinical models and scratching behavior, a key itch endpoint, is often neglected. One such model is the widely used imiquimod (IMQ) mouse model of psoriasis. However, it lacks characterized behavioral attributes like scratching, nor has widely expanded to other species like rats. Given these important attributes, this study was designed to broaden the characterization beyond the expected IMQ-induced psoriasis-like skin inflammatory skin changes and to validate the role of a potential therapeutic agent for pruritus in our genetic rat model. The study included female Wistar rats and genetically modified knockin (humanized proteinase-activated receptor 2 (F2RL1) female rats, with the widely used C57BL/6 J mice as a methodology control for typical IMQ dosing. RESULTS: We demonstrate that the IMQ model can be reproduced in rats, including their genetically modified derivatives, and how scratching can be used as a key behavioral endpoint. We systemically delivered an anti-PAR2 antibody (P24E1102) which reversed scratching bouts-validating this behavioral methodology and have shown its feasibility and value in identifying effective antipruritic drugs.

Adaptability to eccentric exercise training is diminished with age in female mice.

The ability of skeletal muscle to adapt to eccentric contractions has been suggested to be blunted in older muscle. If eccentric exercise is to be a safe and efficient training mode for older adults, preclinical studies need to establish if older muscle can effectively adapt and if not, determine the molecular signatures that are causing this impairment. The purpose of this study was to quantify the extent age impacts functional adaptations of muscle and identify genetic signatures associated with adaptation (or lack thereof). The anterior crural muscles of young (4 mo) and older (28 mo) female mice performed repeated bouts of eccentric contractions in vivo (50 contractions/wk for 5 wk) and isometric torque was measured across the initial and final bouts. Transcriptomics was completed by RNA-sequencing 1 wk following the fifth bout to identify common and differentially regulated genes. When torques post eccentric contractions were compared after the first and fifth bouts, young muscle exhibited a robust ability to adapt, increasing isometric torque 20%-36%, whereas isometric torque of older muscle decreased up to 18% (P ≤ 0.047). Using differential gene expression, young and older muscles shared some common transcriptional changes in response to eccentric exercise training, whereas other transcripts appeared to be age dependent. That is, the ability to express particular genes after repeated bouts of eccentric contractions was not the same between ages. These molecular signatures may reveal, in part, why older muscles do not appear to be as adaptive to exercise training as young muscles.NEW & NOTEWORTHY The ability to adapt to exercise training may help prevent and combat sarcopenia. Here, we demonstrate young mouse muscles get stronger whereas older mouse muscles become weaker after repeated bouts of eccentric contractions, and that numerous genes were differentially expressed between age groups following training. These results highlight that molecular and functional plasticity is not fixed in skeletal muscle with advancing age, and the ability to handle or cope with physical stress may be impaired.

Preventive therapy with galcanezumab for two consecutive cluster bouts in patients with episodic cluster headache: an observational multicenter study.

BACKGROUND: Cluster headache is a severe and disabling primary headache disorder. Galcanezumab is a monoclonal antibody against calcitonin gene-related peptide and a preventive therapy for episodic cluster headache. However, the approval and insurance coverage for episodic cluster headache differ in each country. Additionally, the consistency of efficacy of galcanezumab therapy has not yet been evaluated. This study aimed to assess the efficacy and safety of 240 mg of galcanezumab therapy for consecutive cluster bouts in patients with episodic cluster headache. METHODS: The study enrolled patients with episodic cluster headache who received two courses of galcanezumab therapy at three university hospitals in Republic of Korea between February 2020 and April 2022. The efficacy and safety of galcanezumab were analyzed by comparing daily headache frequency, the number of headache days, and headache intensity and adverse effects during the one-week period before and the third week after galcanezumab injection for each episode of cluster bouts. Paired t-test was used for comparing repeated data from different episodes of cluster bout. RESULTS: Sixteen patients were enrolled in this study. Fourteen patients received galcanezumab therapy for two consecutive cluster bouts. Galcanezumab was administered 24 days and 11 days after the first and second cluster bouts, respectively. The proportion of patients with 50% or more reduction in frequency of daily headache at week 3 from baseline was 86% and 64% during the first and second episodes, respectively. The proportion of patients who received transitional therapy before galcanezumab therapy was higher in the first episode of cluster bout than that in the second episode of cluster bout. No serious adverse reactions or significant differences in adverse effects between cluster bouts were noticed. Two patients received a second galcanezumab therapy during the pre-cluster period, and their cluster periods ended without typical cluster headache attacks 10-60 days after galcanezumab therapy. CONCLUSIONS: This exploratory analysis suggests that galcanezumab may be effective as a preventive therapy in subsequent cluster bouts. Patients with episodic cluster headaches who underwent galcanezumab therapy tended to receive a second round of treatment in the early stages of their next cluster bout without transitional therapy.

Epidemiology, burden and clinical spectrum of cluster headache: a global update.

BACKGROUND: This narrative review aims to broaden our understanding of the epidemiology, burden and clinical spectrum of cluster headache based on updated findings with a global perspective. METHODS: We conducted a literature search on the following topics: (a) epidemiology; (b) burden: quality of life, disability, economic burden, job-related burden and suicidality; and (c) clinical spectrum: male predominance and its changes, age, pre-cluster and pre-attack symptoms, aura, post-drome, attack characteristics (location, severity, duration and associated symptoms), bout characteristics (attack frequency, bout duration and bout frequency), circadian and seasonal rhythmicity and disease course. RESULTS: New large-scale population-based reports have suggested a lower prevalence than previous estimations. The impact of cluster headache creates a significant burden in terms of the quality of life, disability, economic and job-related burdens and suicidality. Several studies have reported decreasing male-to-female ratios and a wide age range at disease onset. The non-headache phases of cluster headache, including pre-cluster, pre-attack and postictal symptoms, have recently been revisited. The latest data regarding attack characteristics, bout characteristics, and circadian and seasonal rhythmicity from different countries have shown variability among bouts, attacks, individuals and ethnicities. Studies on the disease course of cluster headache have shown typical characteristics of attacks or bouts that decrease with time. CONCLUSIONS: Cluster headache may be more than a "trigeminal autonomic headache" because it involves complex central nervous system phenomena. The spectrum of attacks and bouts is wider than previously recognised. Cluster headache is a dynamic disorder that evolves or regresses over time.

Prolonged Sedentary Bouts Are Critically Involved in All-Cause Mortality in Patients on Chronic Hemodialysis: A Prospective Cohort Study.

We investigated the link between prolonged sedentary bouts and all-cause mortality in patients on chronic hemodialysis, using a prospective cohort. A total of 104 outpatients on chronic hemodialysis from 2013 to 2019, aged 71.4±11.4 years, were enrolled. Prolonged sedentary bouts (≥ 30 min and ≥60 min) (min and bouts) and relative prolonged sedentary bouts (≥ 30 min and ≥ 60 min) (%) on the patients' non-hemodialysis days were measured by a tri-accelerometer, and we also analyzed the patients' clinical parameters. The relationship between prolonged sedentary bouts and all-cause mortality was evaluated by a survival analysis and the Cox proportional hazard model. Thirty-five patients died during the follow-up period. A Kaplan-Meier analysis detected significant differences in the survival rate between two groups stratified by the median for all prolonged sedentary-bout parameters. After the adjustment for confounding factors, all of the prolonged sedentary-bout parameters were determinant factors for all-cause mortality. These results indicate that prolonged sedentary bouts on non-hemodialysis days were closely related to all-cause mortality in the patients on hemodialysis.

The Contralateral Repeated Bout Effect of Elbow Flexors Is Not Observed in Young Women Following Mild Muscle Damage from Eccentric Exercises.

Investigation of the contralateral repeated bout effect (CL-RBE) in women is scarce. Therefore, this study aimed at examining whether CL-RBE exists in women. Twelve healthy women (age: 20.9 ± 2.5 years) performed two bouts of maximal elbow flexor eccentric exercise (3 sets × 15 repetitions per bout) separated by 14 days, using the opposite arms. Surface Electromyography (EMG) was recorded during both exercise bouts. The isokinetic muscle strength (60°/s), muscle soreness, range of motion (ROM), limb girth, and blood creatine kinase activity were measured pre-exercise, and at 24 and 48 h post-exercise with the muscle strength being measured immediately post-exercise as well. Significant main effects of time were observed for muscle strength, muscle soreness and ROM (p < 0.05). There were no significant differences between bouts for all the measured variables including the EMG median frequency (p > 0.05). These results suggest that the CL-RBE of elbow flexors was not evident in young healthy women. This was because the mild muscle damage induced by the initial bout of exercise was either not enough to initiate the CL-RBE or the CL-RBE in women lasted shorter than two weeks. This study provides important information for future studies on CL-RBE in women.