Fe-Ni-based alloys as highly active and low-cost oxygen evolution reaction catalyst in alkaline media.

NiFe-based oxo-hydroxides are highly active for the oxygen evolution reaction but require complex synthesis and are poorly durable when deposited on foreign supports. Herein we demonstrate that easily processable, Earth-abundant and cheap Fe-Ni alloys spontaneously develop a highly active NiFe oxo-hydroxide surface, exsolved upon electrochemical activation. While the manufacturing process and the initial surface state of the alloys do not impact the oxygen evolution reaction performance, the growth/composition of the NiFe oxo-hydroxide surface layer depends on the alloying elements and initial atomic Fe/Ni ratio, hence driving oxygen evolution reaction activity. Whatever the initial Fe/Ni ratio of the Fe-Ni alloy (varying between 0.004 and 7.4), the best oxygen evolution reaction performance (beyond that of commercial IrO2) and durability was obtained for a surface Fe/Ni ratio between 0.2 and 0.4 and includes numerous active sites (high NiIII/NiII capacitive response) and high efficiency (high Fe/Ni ratio). This knowledge paves the way to active and durable Fe-Ni alloy oxygen-evolving electrodes for alkaline water electrolysers.

Divergent directed evolution of a TetR-type repressor towards aromatic molecules.

Reprogramming cellular behaviour is one of the hallmarks of synthetic biology. To this end, prokaryotic allosteric transcription factors (aTF) have been repurposed as versatile tools for processing small molecule signals into cellular responses. Expanding the toolbox of aTFs that recognize new inducer molecules is of considerable interest in many applications. Here, we first establish a resorcinol responsive aTF-based biosensor in Escherichia coli using the TetR-family repressor RolR from Corynebacterium glutamicum. We then perform an iterative walk along the fitness landscape of RolR to identify new inducer specificities, namely catechol, methyl catechol, caffeic acid, protocatechuate, L-DOPA, and the tumour biomarker homovanillic acid. Finally, we demonstrate the versatility of these engineered aTFs by transplanting them into the model eukaryote Saccharomyces cerevisiae. This work provides a framework for efficient aTF engineering to expand ligand specificity towards novel molecules on laboratory timescales, which, more broadly, is invaluable across a wide range of applications such as protein and metabolic engineering, as well as point-of-care diagnostics.

Disappearance and dissemination of sleep symptoms: the importance of sleep medicine expertise for psychiatry. A comment on Forbes et al.

Commentary of 'Elemental psychopathology: distilling constituent symptoms and patterns of repetition in the diagnostic criteria of the DSM-5' Vincent P. Martin 1, Régis Lopez 2,3, Jean-Arthur Micoulaud-Franchi 4,5, Christophe Gauld 4,6,.

Prediction of Surface Segregation of Fluorinated Additives from Measurement of Wettability Properties of Polymer-Based Blends.

The aim of this work is to describe the segregation phenomenon of random perfluorinated copolymers toward the surface of a polystyrene (PS) matrix. Three random perfluorinated copolymers, named POISE-a (Polymer prOcessing Interface StabilizEr), synthesized with different amounts of chemically bound fluorine, were mixed with a commercial PS matrix by a solvent casting process. Their effect on the wettability properties of PS as a function of their concentration was measured first under static conditions with different liquids (water, formamide, diethylene glycol) and then under dynamic conditions with water. The evolution of the cosine of the static and dynamic advancing contact angles as a function of the fluorine content by weight in the bulk was predicted using an original physical law, in which the different parameters were related to the morphology of the additivated polymers as revealed by experimental X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy-energy dispersive X-ray (SEM-EDX) measurements. This law has been successfully used to predict the wetting properties of other polymer blends and has contributed to a better understanding of the phase segregation mechanism of additives migrating to the PS surface, at the origin of the increase in hydrophobicity.

Motor disorders related to oxaliplatin-induced peripheral neuropathy: long-term severity and impact on quality of life.

PURPOSE: Sensory chemotherapy-induced peripheral neuropathy (CIPN) is well-recognized, but motor CIPN remains understudied. This secondary analysis focused on the long-term severity and impact of motor disorders, their relation to sensory CIPN, neuropathic pain, psychological distress, and health-related quality of life (HRQoL) after oxaliplatin-based chemotherapy in colorectal cancer (CRC) survivors. METHODS: Data from a multicenter, cross-sectional study were re-analyzed to explore motor CIPN among CRC survivors up to 5 years post-chemotherapy, with no longitudinal follow-up. Questionnaires assessed sensory and motor CIPN (QLQ-CIPN20), neuropathic pain (DN4), anxiety and depression (HADS), and HRQoL (QLQ-C30). RESULTS: Among 405 CRC survivors, 31.1% had sensory CIPN as previously described. When categorizing the 405 CRC survivors based on the years since their last oxaliplatin-based chemotherapy, the motor scores derived from the QLQ-CIPN20 showed no significant difference between years (p = 0.08). Motor CIPN scores correlated with female gender, higher oxaliplatin dose intensity, sensory CIPN, and neuropathic pain. Motor CIPN also linked to decreased HRQoL and increased psychological distress. CONCLUSION: The study underscores the detrimental impact of motor disorders on CRC survivors post-oxaliplatin-based chemotherapy. Oncologists should prioritize assessing and managing motor manifestations alongside sensory symptoms to enhance post-cancer quality of life. TRIAL REGISTRATION: NCT02970526 (2016-11-22). https://classic. CLINICALTRIALS: gov/ct2/show/NCT02970526?term=NCT02970526&draw=2&rank=1 .

Combined Endurance and Strength or Only Endurance Training? Effects of Training Mode on Neuromuscular Characteristics and Functional Abilities in Obese Adolescent Girls Enrolled in a Weight-Reduction Program.

The aim of the present study was to examine whether combining strength and endurance training would promote better improvements in neuromuscular characteristics and functional abilities than endurance training alone in obese adolescent girls enrolled in a weight-reduction program. Twenty-four obese adolescent girls (12-15 years) volunteered to participate in a 9-month training program. Participants were allocated into two groups following either (i) combined training (endurance + strength; E+ST) or (ii) endurance training (ET) program. Absolute and specific maximal torque, muscle size, and maximal voluntary activation level (VA) of the knee extensor (KE) and plantar flexor (PF) muscles were assessed. Moreover, functional abilities such as balance and fatigability during a maximal isometric intermittent contraction test of the KE muscles were measured before and after the intervention. The force of the adductor pollicis (AP) muscles was used as a control to account for any effect of growth or mechanical unloading on neuromuscular properties and muscle size. While absolute and specific torque of the KE (+14.7 ± 12.1% and +14.4 ± 15.5%; p < 0.05) and PF (+19.2 ± 16.7% and +18.3 ± 17.5%; p < 0.001) muscles increased in the E+ST group, PF torque decreased, and KE torque did not change in the ET group (-22.6 ± 10.5% and -15.0 ± 17.2%; p < 0.001). Moreover, the VA of the KE muscles increased for the E+ST (+6.1 ± 5.6%; p < 0.01) group and decreased for the ET group (-5.4 ± 5.4%; p < 0.05). In contrast, VA remained similar in the PF muscles for both groups. The number of repetitions during the fatigability test increased in the ET group (38.4 ± 22.3 vs. 84.1 ± 33.3; p = 0.032) and was unchanged in the E+ST group (50.8 ± 14.1 vs. 54.2 ± 37.8), but it was associated with a higher force level. Moreover, balance improved in the E+ST group, but not in the ET group. To conclude, physical training combining strength and endurance training promoted larger improvement in neuromuscular characteristics and functional abilities than endurance training alone in obese adolescent girls. Greater neuromuscular adaptations resulting from the E+ST training may be beneficial for preserving or even increasing functional abilities and possibly induce greater engagement in the active lifestyle of obese adolescents. However, the endurance component seems necessary in training programs to reduce fatigability during daily living activities.

Sex-Related Neuromuscular Adaptations to Youth Obesity: Force, Muscle Mass, and Neural Issues.

Young obese are generally stronger than their typically developing counterparts. Strength differences could be partly ascribed to nervous adaptations, due to the loading effect of carrying overweight. We hypothesized that central adaptations of the muscles highly involved in weight bearing, i.e., plantar flexors (PF) and knee extensors (KE) could be greater in girls than boys due to their reduced potential for muscle hypertrophy. Furthermore, it is possible that neuromuscular adaptations in weight-bearing muscles will be greater compared to the unloaded muscles such as the adductor pollicis (AP).Twenty-four non-obese and 21 obese (body mass index: 33 ± 4 kg·m-2) adolescent girls and boys (12-15 years) performed maximal voluntary isometric contractions (MVC) of the PF and KE muscles. Voluntary activation (VA), assessed with the twitch interpolation technique, the antagonist co-activation (Co-Act) level, and the normalized root-mean-square value (RMS) of the agonist muscles were measured to account for central adaptations.The results revealed a weight status effect (p < 0.001) on the absolute MVC torque and VA of both KE and PF muscles. Moreover, these differences were also related to the sex of the participants (p < 0.05) for the PF muscles. While the VA, absolute, and specific MVC torque were greater in obese compared with non-obese girls, no difference was found between boys. A similar Co-Act level was observed between groups, whatever the sex and muscle group considered. Finally, no significant differences were found for the AP regarding peripheral and neural factors.This study highlighted a favorable effect of obesity on the central mechanisms (i.e., VA) responsible for force production within the lower limb muscles. However, obesity-related central adaptation was only observed in girls for the PF muscles. Thus, the excess of body mass supported by the muscles involved in weight-bearing could act as a chronic training stimulus responsible for these adaptations in obese adolescents but mostly in girls.

Is Physical Activity an Efficient Strategy to Control the Adverse Effects of Persistent Organic Pollutants in the Context of Obesity? A Narrative Review.

Obesity affects nearly 660 million adults worldwide and is known for its many comorbidities. Although the phenomenon of obesity is not fully understood, science regularly reveals new determinants of this pathology. Among them, persistent organic pollutants (POPs) have been recently highlighted. Mainly lipophilic, POPs are normally stored in adipose tissue and can lead to adverse metabolic effects when released into the bloodstream. The main objective of this narrative review is to discuss the different pathways by which physical activity may counteract POPs' adverse effects. The research that we carried out seems to indicate that physical activity could positively influence several pathways negatively influenced by POPs, such as insulin resistance, inflammation, lipid accumulation, adipogenesis, and gut microbiota dysbiosis, that are associated with the development of obesity. This review also indicates how, through the controlled mobilization of POPs, physical activity could be a valuable approach to reduce the concentration of POPs in the bloodstream. These findings suggest that physical activity should be used to counteract the adverse effects of POPs. However, future studies should accurately assess its impact in specific situations such as bariatric surgery, where weight loss promotes POPs' blood release.

CRISPR-Cas tools to study gene function in cytokinesis.

Cytokinesis is the process that separates a cell into two daughter cells at the end of mitosis. Most of our knowledge of cytokinesis comes from overexpression studies, which affects our interpretation of protein function. Gene editing can circumvent this issue by introducing functional mutations or fluorescent probes directly into a gene locus. However, despite its potential, gene editing is just starting to be used in the field of cytokinesis. Here, we discuss the benefits of using gene editing tools for the study of cytokinesis and highlight recent studies that successfully used CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) technology to answer critical questions regarding the function of cytokinesis proteins. We also present methodologies for editing essential genes and discuss how CRISPR interference (CRISPRi) and activation (CRISPRa) can enable precise control of gene expression to answer important questions in the field. Finally, we address the need for gene editing to study cytokinesis in more physiologically relevant contexts. Therefore, this Review provides a roadmap for gene editing to be used in the study of cytokinesis and other cellular processes.

Pathway elucidation and microbial synthesis of proaporphine and bis-benzylisoquinoline alkaloids from sacred lotus (Nelumbo nucifera).

Sacred lotus (Nelumbo nucifera) has been utilized as a food, medicine, and spiritual symbol for nearly 3000 years. The medicinal properties of lotus are largely attributed to its unique profile of benzylisoquinoline alkaloids (BIAs), which includes potential anti-cancer, anti-malarial and anti-arrhythmic compounds. BIA biosynthesis in sacred lotus differs markedly from that of opium poppy and other members of the Ranunculales, most notably in an abundance of BIAs possessing the (R)-stereochemical configuration and the absence of reticuline, a major branchpoint intermediate in most BIA producers. Owing to these unique metabolic features and the pharmacological potential of lotus, we set out to elucidate the BIA biosynthesis network in N. nucifera. Here we show that lotus CYP80G (NnCYP80G) and a superior ortholog from Peruvian nutmeg (Laurelia sempervirens; LsCYP80G) stereospecifically convert (R)-N-methylcoclaurine to the proaporphine alkaloid glaziovine, which is subsequently methylated to pronuciferine, the presumed precursor to nuciferine. While sacred lotus employs a dedicated (R)-route to aporphine alkaloids from (R)-norcoclaurine, we implemented an artificial stereochemical inversion approach to flip the stereochemistry of the core BIA pathway. Exploiting the unique substrate specificity of dehydroreticuline synthase from common poppy (Papaver rhoeas) and pairing it with dehydroreticuline reductase enabled de novo synthesis of (R)-N-methylcoclaurine from (S)-norcoclaurine and its subsequent conversion to pronuciferine. We leveraged our stereochemical inversion approach to also elucidate the role of NnCYP80A in sacred lotus metabolism, which we show catalyzes the stereospecific formation of the bis-BIA nelumboferine. Screening our collection of 66 plant O-methyltransferases enabled conversion of nelumboferine to liensinine, a potential anti-cancer bis-BIA from sacred lotus. Our work highlights the unique benzylisoquinoline metabolism of N. nucifera and enables the targeted overproduction of potential lotus pharmaceuticals using engineered microbial systems.

Circulating microRNA levels after exercise-induced muscle damage and the repeated bout effect.

The neuromuscular system can quickly adapt to exercise-induced muscle damage (EIMD), such that it is less affected by subsequent damaging exercise, a phenomenon known as the repeated bout effect (RBE). Circulating muscle-specific microRNAs (myomiRs) may be able to potentially predict the long-lasting maximal voluntary contraction (MVC) torque deficit (>24 h), an indicator of EIMD. We aimed to investigate: 1) how plasma myomiR levels are modified by the RBE and 2) whether plasma myomiRs can predict the long-lasting MVC torque deficit. Nineteen participants performed two identical bouts of loaded downhill walking separated by 2 wk. MVC torque, creatine kinase (CK) activity, myoglobin (Mb) concentration, and myomiR levels were measured before and up to 48 h after exercise. Correlation and multiple regression analyses were performed to assess the ability of these markers to predict the largest MVC torque loss beyond 24 h postexercise. Similar to MVC torque, CK activity, and the Mb concentration, the relative abundance of certain myomiRs (hsa-miR-1-3p, and hsa-miR-133a-3p) was less affected after the second bout of exercise relative to the first bout. The CK activity, Mb concentration, and level of several myomiRs (hsa-miR-1-3p, hsa-miR-133a-3p, and hsa-miR-206) correlated with long-lasting MVC torque loss. Multiple regression showed that the best combination of markers to predict the long-lasting deficit of MVC torque included several myomiRs, Mb, and CK. Certain myomiR levels increased less after exercise bout 2 than after exercise bout 1, indicating the presence of the RBE. The measurement of myomiR levels in combination with Mb concentrations and CK activity could improve the prediction of the long-lasting MVC torque deficit.NEW & NOTEWORTHY The present study is the first to show that plasma muscle-specific microRNA (myomiR) levels can be modified by the repeated bout effect, as their levels increased less after the second exercise bout relative to the first. This study is also the first to suggest that myomiR levels could be used to partially predict maximal voluntary contraction torque loss at 24 h postexercise (i.e., the magnitude of exercise-induced muscle damage). Interestingly, the combined measurement of certain myomiR levels with those of myoglobin and creatine kinase improved the predictive value.

Contractile properties are less affected at long than short muscle length after eccentric exercise.

PURPOSE: The aim of the present study was to investigate whether the electrically evoked muscle responses are differently affected over time by the knee joint angle after an exercise-induced muscle damage (EIMD). We hypothesized that low-frequency-evoked responses would be less affected at long than short muscle length, and that mechanisms located within the muscle and tendinous tissues would be involved. METHODS: Fifteen males performed 45 min loaded downhill walking (DW) exercise. Maximal voluntary contraction torque (MVC), optimal angle for torque production, voluntary activation level (VAL), twitch, doublet at 10 and 100 Hz (Db10 and Db100, respectively), rate of torque development (RTD), post-activation potentiation (PAP), muscle shear elastic modulus (µ) and aponeurosis stiffness were assessed before, after, and 4, 24, 48, 72 and 168 h after the exercise at a knee angle of 40°, 90° and 120° (0°: full extension). RESULTS: MVC, VAL and Db100 were similarly decreased across joint angles after the DW and optimal angle was not affected. Twitch, Db10, Db10/Db100, PAP and RTD were less affected and muscle µ more increased at long than short muscle lengths (p < 0.05), especially during the first 24 h after the DW exercise. CONCLUSION: Low-frequency-evoked responses were more preserved at long than short muscle length the first 24 h after the DW exercise, suggesting that joint angle should be taken into account to assess muscular alterations after EIMD. This length-dependence could be associated to the higher sensitivity to Ca2+ and the higher increase in muscle stiffness at long than short muscle length.

Quantification of Extramyocellular Lipids and Intramuscular Fat from Muscle Echo Intensity in Lower Limb Muscles: A Comparison of Four Ultrasound Devices against Magnetic Resonance Spectroscopy.

This study aimed to compare different ultrasound devices with magnetic resonance spectroscopy (MRS) to quantify muscle lipid content from echo intensity (EI). Four different ultrasound devices were used to measure muscle EI and subcutaneous fat thickness in four lower-limb muscles. Intramuscular fat (IMF), intramyocellular (IMCL) and extramyocellular lipids (EMCL) were measured using MRS. Linear regression was used to compare raw and subcutaneous fat thickness-corrected EI values to IMCL, EMCL and IMF. IMCL had a poor correlation with muscle EI (r = 0.17-0.32, NS), while EMCL (r = 0.41-0.84, p < 0.05-p < 0.001) and IMF (r = 0.49-0.84, p < 0.01-p < 0.001) had moderate to strong correlation with raw EI. All relationships were improved when considering the effect of subcutaneous fat thickness on muscle EI measurements. The slopes of the relationships were similar across devices, but there were some differences in the y-intercepts when raw EI values were used. These differences disappeared when subcutaneous fat thickness-corrected EI values were considered, allowing for the creation of generic prediction equations (r = 0.41-0.68, p < 0.001). These equations can be used to quantify IMF and EMCL within lower limb muscles from corrected-EI values in non-obese subjects, regardless of the ultrasound device used.

Predictive models for determining treatment response to nonprescription acute medications in migraine: Results from the American Migraine Prevalence and Prevention Study.

OBJECTIVE: To identify predictors of acute treatment response for nonprescription (over-the-counter [OTC]) medications among people with migraine and develop improved models for predicting treatment response. BACKGROUND: Pain freedom and sustained pain relief are important priorities in the acute treatment of migraine. OTC medications are widely used for migraine; however, it is not clear which treatment works best for each patient without going through the trial and error process. METHODS: A prediction model development study was completed using the 2006 American Migraine Prevalence and Prevention Study survey, from participants who were aged ≥18, met criteria and headache day frequency for episodic migraine, did not take prescription medication for migraine, and used ≥1 of the following acute migraine medication classes: acetaminophen, aspirin, NSAIDs, or caffeine containing combination products (CCP). Two items from the Migraine Treatment Optimization Questionnaire were used to evaluate treatment response, adequate 2-h pain freedom (2hPF) and 24-h pain relief (24hPR), which were defined by a response to treatment ≥half the time at 2 h and 24 h post treatment, respectively. We identified predictors of adequate treatment response and developed models to predict probability of treatment response to each medication class. RESULTS: The sample included 3852 participants (3038 [79.0%] females) with an average age of 45.0 years (SD = 12.8). Only 1602/3852 (41.6%) and 1718/3852 (44.6%) of the participants reported adequate 2hPF and 24hPR, respectively. Adequate treatment-response was significantly predicted by lower average headache pain intensity, less cutaneous allodynia, and lower depressive symptom scores. Lower migraine symptom severity was predictive of adequate 2hPF and fewer monthly headache days was predictive of adequate 24hPR. Among participants reporting OTC monotherapy (n = 2168, 56.3%) individuals taking CCP were more likely to have adequate 2hPF (OR = 1.55, 95% CI 1.23-1.95) and 24hPR (OR = 1.79, 95% CI 1.18-1.88) in comparison with those taking acetaminophen. Predictive models were modestly predictive of responders to OTC medications (c-statistics = 0.65; 95% CI 0.62-0.68). CONCLUSION: These results show that response to acute migraine treatments is not optimized in the majority of people with migraine treating with OTC medications. Predictive models can improve our ability to choose the best therapeutic option for individuals with episodic migraine and increase the proportion of patients with optimized response to treatments.

Eptinezumab for migraine prevention in patients 50 years or older.

OBJECTIVE: To evaluate the efficacy and safety of eptinezumab versus placebo in patients ≥50 years old with episodic (EM) or chronic migraine (CM). MATERIALS AND METHODS: This post hoc analysis included data from two phase 3, parallel-group, randomized, double-blind, placebo-controlled studies in adults with EM (PROMISE-1) or CM (PROMISE-2). Patients ≥50 years at baseline treated with eptinezumab 100 mg, 300 mg, or placebo were pooled from both studies to evaluate efficacy and safety. RESULTS: A total of 385/1960 (19.6%) EM and CM patients who were ≥50 years old at baseline (range, 50-71 and 50-65 years, respectively) received eptinezumab 100 mg (n = 132), 300 mg (n = 127), or placebo (n = 126) over Weeks 1-12. Reductions in mean monthly migraine days (MMDs) in ≥50-year-old EM patients were -3.8 (100 mg) and -4.4 (300 mg) with eptinezumab versus -2.6 with placebo. In ≥50-year-old CM patients, mean changes in MMDs were -7.7 (100 mg) and -8.6 (300 mg) with eptinezumab versus -6.0 with placebo. Changes in MMDs were comparable to total study results. A ≥50% MMD reduction over Weeks 1-12 was achieved by 57.9% of eptinezumab-treated versus 35.7% of patients who received placebo, and a ≥75% reduction by 30.5% versus 13.5%, respectively. The incidence of treatment-emergent adverse events (TEAEs) in EM and CM patients ≥50 years old was similar across treatment groups, with ≥96% of TEAEs mild or moderate in severity. CONCLUSIONS: Treatment with eptinezumab was efficacious, tolerable, and safe in patients ≥50 years with EM or CM, congruent with results from the overall study population.

Beneficial Effects of Linseed Supplementation on Gut Mucosa-Associated Microbiota in a Physically Active Mouse Model of Crohn's Disease.

The Western diet, rich in lipids and in n-6 polyunsaturated fatty acids (PUFAs), favors gut dysbiosis observed in Crohn's disease (CD). The aim of this study was to assess the effects of rebalancing the n-6/n-3 PUFA ratio in CEABAC10 transgenic mice that mimic CD. Mice in individual cages with running wheels were randomized in three diet groups for 12 weeks: high-fat diet (HFD), HFD + linseed oil (HFD-LS-O) and HFD + extruded linseed (HFD-LS-E). Then, they were orally challenged once with the Adherent-Invasive Escherichia coli (AIEC) LF82 pathobiont. After 12 weeks of diet, total energy intake, body composition, and intestinal permeability were not different between groups. After the AIEC-induced intestinal inflammation, fecal lipocalin-2 concentration was lower at day 6 in n-3 PUFAs supplementation groups (HFD-LS-O and HFD-LS-E) compared to HFD. Analysis of the mucosa-associated microbiota showed that the abundance of Prevotella, Paraprevotella, Ruminococcus, and Clostridiales was higher in the HFD-LS-E group. Butyrate levels were higher in the HFD-LS-E group and correlated with the Firmicutes/Proteobacteria ratio. This study demonstrates that extruded linseed supplementation had a beneficial health effect in a physically active mouse model of CD susceptibility. Additional studies are required to better decipher the matrix influence in the linseed supplementation effect.

Central fatigue aetiology in prolonged trail running races.

NEW FINDINGS: What is the central question of this study? Are spinal and/or supraspinal perturbations implicated in central fatigue induced in the plantar flexor muscles following prolonged trail running races? What is the main finding and its importance? The study confirmed the presence of central fatigue following various trail running distances from 40 to 170 km. The reduction in the V-wave in conjunction with the lack of change in the H-reflex suggests that a major component of this central fatigue may arise from supraspinal mechanisms in the plantar flexor muscles. ABSTRACT: Trail running races are known to induce considerable impairments in neuromuscular function of which central mechanisms are a substantial component. However, the loci of this central fatigue (i.e. supraspinal and/or spinal) is not well identified. The aim of this study was to better understand central fatigue aetiology induced in the plantar flexor muscles by various trail running distances from 40 to 170 km. Eighteen runners participated in the study and neuromuscular function of their plantar flexors was tested before (PRE) and after (POST) various races during the Ultra-Trail du Mont Blanc. Neuromuscular function was evaluated with voluntary and evoked contractions using electrical tibial nerve stimulation. H-reflex and V-wave responses were also measured during submaximal and maximal voluntary contraction, respectively. Reductions in maximal voluntary contraction torque (-29%; P < 0.001) and voluntary activation level (-12%; P < 0.001) were observed after trail running races. The V-wave was reduced in soleus (-35%; P = 0.003) and gastrocnemius medialis (-28%; P = 0.031), with no changes for the H-reflex in soleus (P = 0.577). The present study confirmed the presence of central fatigue following trail running exercise. The reduction in the V-wave in conjunction with the lack of change in the H-reflex suggests that a major component of this central fatigue may arise from supraspinal mechanisms.

Determinants of pain interference and headache impact in patients who have chronic migraine with medication overuse: Results from the MOTS trial.

OBJECTIVE: "Pain interference" and "headache impact" refer to negative consequences that pain and headache have on one's life. This study investigated determinants of these negative impacts in a large patient cohort who have chronic migraine with medication overuse. METHODS: Six hundred and eleven adults were enrolled from 34 headache, neurology, and primary care clinics. Negative consequences of chronic migraine with medication overuse were determined using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference 6b questionnaire and the Headache Impact Test 6. Relationships between PROMIS-6b and Headache Impact Test 6 scores with demographics, headache characteristics, medication use, anxiety symptoms, and depression symptoms were assessed with linear regression. Elastic Net regression was used to develop a multiple regression model. RESULTS: PROMIS-6b T-Scores averaged 65.2 (SD 5.4) and Headache Impact Test 6 scores averaged 65.0 (SD 5.3), indicating severe negative consequences of chronic migraine with medication overuse. Chronic migraine with medication overuse interfered with enjoyment of life, concentration, daily activities, doing tasks away from home, and socializing. Depression symptom severity had the strongest relationship with pain interference and headache impact. Moderate-to-severe headache frequency, headache intensity, and anxiety symptoms were also associated with pain interference and headache impact. CONCLUSIONS: Chronic migraine with medication overuse is associated with substantial negative consequences, the extent of which is most strongly related to depression symptoms.

Headache characteristics and burden from chronic migraine with medication overuse headache: Cross-sectional observations from the Medication Overuse Treatment Strategy trial.

OBJECTIVE: To describe headache characteristics, medication use, disability, and quality of life in a large patient cohort from the United States who have chronic migraine (CM) and medication overuse headache (MOH). METHODS: In all, 610 adult patients were enrolled into the Medication Overuse Treatment Strategy trial from 34 healthcare clinics, including headache specialty, general neurology, and primary care clinics. Descriptive statistics characterize baseline demographics, headache characteristics, medication use, disability (Headache Impact Test 6 [HIT-6] and Migraine Functional Impact Questionnaire [MFIQ]), pain interference (PROMIS Pain Interference), and quality of life (EQ-5D-5L). Relationships with headache frequency were assessed. RESULTS: Mean age was 45 years (SD 13) and 531/608 (87.3%) were females. Mean headache days per 30 was 24.3 (SD 5.5), including 13.6 (SD 7.1) with moderate to severe headache. Daily headaches were reported by 36.1% (219/607) of patients. Acute headache medications were used on 21.5 (SD 7.5) per 30 days. The most commonly overused medications were simple analgesics (378/607, 62% of patients), combination analgesics (246/607, 41%), and triptans (128/607, 21%). HIT-6, MFIQ, PROMIS Pain Interference, and EQ-5D-5L scores demonstrated substantial negative impact from CM with MOH on patient functioning and quality of life. Higher headache frequency was associated with more moderate-severe headache days, more frequent acute headache medication use, greater headache-related disability, and lower quality of life. Only 272/606 (44.9%) were taking migraine preventive medication. CONCLUSIONS: CM with MOH is associated with a large burden on patients in the United States. Higher headache frequency is associated with greater impact on functioning, pain interference, and quality of life.

Effect of race distance on performance fatigability in male trail and ultra-trail runners.

The etiology of changes in lower-limb neuromuscular function, especially to the central nervous system, may be affected by exercise duration. Direct evidence is lacking as few studies have directly compared different race distances. This study aimed to investigate the etiology of deficits in neuromuscular function following short versus long trail-running races. Thirty-two male trail runners completed one of five trail-running races as LONG (>100 km) or SHORT (<60 km). Pre- and post-race, maximal voluntary contraction (MVC) torque and evoked responses to electrical nerve stimulation during MVCs and at rest were used to assess voluntary activation and muscle contractile properties of knee-extensor (KE) and plantar-flexor (PF) muscles. Transcranial magnetic stimulation (TMS) was used to assess evoked responses and corticospinal excitability in maximal and submaximal KE contractions. Race distance correlated with KE MVC (ρ = -0.556) and twitch (ρ = -0.521) torque decreases (p ≤ .003). KE twitch torque decreased more in LONG (-28 ± 14%) than SHORT (-14 ± 10%, p = .005); however, KE MVC time × distance interaction was not significant (p = .073). No differences between LONG and SHORT for PF MVC or twitch torque were observed. Maximal voluntary activation decreased similarly in LONG and SHORT in both muscle groups (p ≥ .637). TMS-elicited silent period decreased in LONG (p = .021) but not SHORT (p = .912). Greater muscle contractile property impairment in longer races, not central perturbations, contributed to the correlation between KE MVC loss and race distance. Conversely, PF fatigability was unaffected by race distance.