Endurance training improves oxygen uptake/demand mismatch, metabolic flexibility and recovery in patients with sickle cell disease.

Patients with sickle cell disease (SCD) display lower slope coefficients of the oxygen uptake (V_O2) vs. work rate (W) relationship (delineating an O2 uptake/demand mismatch) and a poor metabolic flexibility. Because endurance training (ET) increases the microvascular network and oxidative enzymes activity including one involved in lipid oxidation, ET might improve the slope coefficient of the V_O2 vs. W curve and the metabolic flexibility of SCD patients. ET may also contribute to improve patient post-exercise cardiopulmonary and metabolic recovery. Fifteen patients with SCD performed a submaximal incremental test on a cycle ergometer before (SIT1) and after (SIT2) 8 weeks of ET. Minute ventilation, ventilation rate (VR), heart rate (HR), V_O2, CO2 production, respiratory exchange ratio, carbohydrate/lipid utilization and partitioning (including %Lipidox) and blood lactate concentration ([lactate]b) were measured during and after SIT1 and SIT2. At baseline, the slope coefficient of the V_O2 vs. W curve positively correlated with total hemoglobin, mean corpuscular hemoglobin and percentage of HbF. After training, the slope coefficient of the V_O2 vs. W curve was significantly higher and the [lactate]b increase was delayed. If patients' energy metabolism apparently relied largely on carbohydrate sources during SIT1, %Lipidox tended to increase at low exercise intensities during SIT2, supporting a training-induced improvement of metabolic flexibility in patients with SCD. Post-exercise recovery of VR, V_E/V_CO2, HR and [lactate]b was faster after training. We concluded that ET in patients with SCD i) ameliorated the oxygen uptake/demand mismatch, ii) blunted the metabolic inflexibility, and iii) improved post-exercise cardiopulmonary and metabolic responses.

Soft-Tissue Vibrations and Fatigue During Prolonged Running: Does an Individualized Midsole Hardness Play a Role?

Footwear has the potential to reduce soft-tissue vibrations (STV) but responses are highly subject-specific. Recent evidence shows that compressive garments minimizing STV have a beneficial effect on neuromuscular (NM) fatigue. The aim was to determine whether an individualized midsole hardness can minimize STV and NM fatigue during a half marathon. Twenty experienced runners were recruited for three visits: a familiarization session including the identification of midsole minimizing and maximizing STV amplitude (MIN and MAX, respectively), and two half marathon sessions at 95% of speed at the second ventilatory threshold. STV of the gastrocnemius medialis (GM) muscle, running kinetics, foot strike pattern, rating perceived exhaustion (RPE), and midsole liking were recorded every 3 km. NM fatigue was assessed on plantar flexors (PF) before (PRE) and after (POST) the half marathon. At POST, PF central and peripheral alterations and changes in contact time, step frequency, STV median frequency, and impact force frequency as well as foot strike pattern were found in both MIN and MAX. No significant differences in damping, STV main frequency, flight time, duty factor, and loading rate were observed between conditions whatever the time period. During the half marathon, STV amplitude of GM significantly increased over time for the MAX condition (+13.3%) only. Differences between MIN and MAX were identified for RPE and midsole liking. It could be hypothesized that, while significant, the effect of midsole hardness on STV is too low to substantially affect NM fatigue.

Occurrence of focal myositis during Behçet's disease: The identification of a specific vasculitis-associated focal myopathy.

AIMS: This study aimed to report the association of focal myositis (FM) and Behçet's disease (BD) and to analyse the main characteristics of such an association. METHODS: This is a retrospective multicentre study of patients with BD and FM (BD + FM+ group) and those without FM (BD - FM+ group). Clinical, laboratory, radiological, pathological, treatment and outcome data were analysed. RESULTS: The BD + FM+ group included 10 patients; the median [interquartile range] age at BD diagnosis was 25 [16-35] years, and at FM diagnosis, it was 30 [26-42] years. The diagnosis of BD preceded FM in the majority of cases (n = 8/10). FM occurrence was associated with BD flare-ups in three cases. The creatine kinase levels remained normal or slightly increased. Histological analyses identified relatively preserved muscle tissue, associated with vasculitis (n = 5/6). All patients required treatment; most patients relapsed (n = 9/10). The BD - FM+ group included 35 patients. A comparison of the groups identified a trend towards a younger median age at diagnosis of FM among those with BD (p = 0.063) and more frequent focal muscle swelling in the BD + FM+ group (p = 0.029). The pathological analysis identified significantly less frequent muscle alterations in the BD + FM+ group (muscle fibre size heterogeneity, p = 0.021; necrosis, p = 0.007; and fibrosis, p = 0.027). BD + FM+ patients had a higher frequency of relapse (p = 0.003) and systematic treatment (p = 0.042). CONCLUSIONS: FM occurring during BD appears to be part of the systemic vasculitis process and presents as a vasculitis-associated focal myopathy with a specific clinico-histological pattern. Patients with this association require long-term follow-up and adapted management. This case series also highlights the need for research on BD diagnostic criteria in cases of FM.

Neuromuscular and autonomic function is fully recovered within 24 h following a sprint interval training session.

BACKGROUND: Recovery is a key factor to promote adaptations and enhance performance. Sprint Interval Training (SIT) is known to be an effective approach to improve overall physical function and health. Although a 2-day rest period is given between SIT sessions, the time-course of recovery after SIT is unknown. PURPOSE: The aim of this study was to determine whether the neuromuscular and autonomic nervous systems would be impaired 24 and 48 h after an SIT session. METHODS: Twenty-five healthy subjects performed an 8 × 15 s all-out session on a braked cycle ergometer with 2 min of rest between repetitions. Isometric maximal voluntary contraction (iMVC) and evoked forces to electrical nerve stimulation during iMVC and at rest were used to assess muscle contractile properties and voluntary activation before (Pre), 1 (Post24h), and 2 (Post48h) days after the session. Two maximal 7 s sprints with two different loads were performed at those same time-points to evaluate the maximal theoretical force (F0), velocity (V0) and maximal power (Pmax) production during a dynamic exercise. Additionally, nocturnal heart rate variability (HRV) was assessed the previous and the three subsequent nights to the exercise bout. RESULTS: No significant impairments were observed for the iMVC or for the force evoked by electrical stimulation 1 day after the session. Similarly, F0, V0, and Pmax were unchanged at Post24h and Post48h. Furthermore, HRV did not reveal any temporal or frequential significant difference the nights following SIT compared to Pre. CONCLUSION: The results of this study show a full recovery of neuromuscular and autonomic functions a day after an all-out SIT session.

Cardiorespiratory Fitness and Neuromuscular Function of Mechanically Ventilated ICU COVID-19 Patients.

OBJECTIVES: The aim of the current study was to investigate the level of cardiorespiratory fitness and neuromuscular function of ICU survivors after COVID-19 and to examine whether these outcomes are related to ICU stay/mechanical ventilation duration. DESIGN: Prospective nonrandomized study. SETTING: Patients hospitalized in ICU for COVID-19 infection. PATIENTS: Sixty patients hospitalized in ICU (mean duration: 31.9 ± 18.2 d) were recruited 4-8 weeks post discharge from ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients visited the laboratory on two separate occasions. The first visit was dedicated to quality of life questionnaire, cardiopulmonary exercise testing, whereas measurements of the knee extensors neuromuscular function were performed in the second visit. Maximal oxygen uptake (V o2 max) was 18.3 ± 4.5 mL·min -1 ·kg -1 , representing 49% ± 12% of predicted value, and was significantly correlated with ICU stay/mechanical ventilation (MV) duration ( R = -0.337 to -0.446; p < 0.01 to 0.001), as were maximal voluntary contraction and electrically evoked peak twitch. V o2 max (either predicted or in mL· min -1 ·kg -1 ) was also significantly correlated with key indices of pulmonary function such as predicted forced vital capacity or predicted forced expiratory volume in 1 second ( R = 0.430-0.465; p ≤ 0.001) and neuromuscular function. Both cardiorespiratory fitness and neuromuscular function were correlated with self-reported physical functioning and general health status. CONCLUSIONS: V o2 max was on average only slightly above the 18 mL·min -1 ·kg -1 , that is, the cut-off value known to induce difficulty in performing daily tasks. Overall, although low physical capacities at admission in ICU COVID-19 patients cannot be ruled out to explain the association between V o2 max or neuromuscular function and ICU stay/MV duration, altered cardiorespiratory fitness and neuromuscular function observed in the present study may not be specific to COVID-19 disease but seem applicable to all ICU/MV patients of similar duration.

Sex-related differences and effects of short and long trail running races on resting muscle-tendon mechanical properties.

The purpose of the study was to assess sex-related differences in resting mechanical properties and adaptations of skeletal muscles and tendons in response to trail running races of different distances using multi-site shear wave elastography assessments of the lower limb, force capacity and blood analyses. Sex differences in resting mechanical properties of knee extensor and plantar flexor muscles and tendons were characterized by shear wave velocity (SWV) measurements in healthy males (N = 42) and females (N = 25) trained in long-distance running. Effects of running distance on muscle and tendon properties were assessed in short (<60 km, N = 23) vs. long (>100 km, N = 26) distance races. Changes in isometric maximal voluntary contraction torque, serum C-reactive protein and creatine kinase activity were also quantified after running races. Higher SWV of relaxed triceps surae muscle was detected in females as compared to males before running races (+4.8%, p = 0.006), but the significant increases in triceps surae muscle group (+7.0%, p = 0.001) and patellar tendon SWV (+15.4%, p = 0.001) after short-distance races were independent of sex. A significant decrease in triceps surae muscle SWV was found after long-distance races in the whole experimental population (-3.1%, p = 0.049). Post-races increase in C-reactive protein and creatine kinase activity were significantly correlated to the relative decreases in triceps surae and quadriceps femoris skeletal muscle SWV (ρ = -0.56, p = 0.001 and ρ = -0.51, p = 0.001, respectively). Resting mechanical properties of muscles and tendons are affected by sex, and adaptations to trail races are related to running distance. Exercise-induced changes in resting skeletal muscle mechanical properties are associated with enhanced indirect markers of inflammation and muscle damage.

Acute effects of quadriceps muscle versus tendon prolonged local vibration on force production capacities and central nervous system excitability.

PURPOSE: The present study aimed to directly compare the effects of 30 min muscle (VIBmuscle) vs. tendon (VIBtendon) local vibration (LV) to the quadriceps on maximal voluntary isometric contraction (MVIC) and rate of torque development (RTD) as well as on central nervous system excitability (i.e. motoneuron and cortical excitability). METHODS: Before (PRE) and immediately after (POST) LV applied to the quadriceps muscle or its tendon, we investigated MVIC and RTD (STUDY #1; n = 20) or vastus lateralis (VL), vastus medialis (VM) and rectus femoris (RF) electromyography responses to thoracic electrical stimulation (TMEPs; motoneuron excitability) and transcranial magnetic stimulation (MEPs; corticospinal excitability) (STUDY #2; n = 17). MEP/TMEP ratios were further calculated to quantify changes in cortical excitability. RESULTS: MVIC decreased at POST (P = 0.017) without any difference between VIBtendon and VIBmuscle, while RTD decreased for VIBtendon (P = 0.013) but not VIBmuscle. TMEP amplitudes were significantly decreased for all muscles (P = 0.014, P < 0.001 and P = 0.004 for VL, VM and RF, respectively) for both LV sites. While no changes were observed for MEP amplitude, MEP/TMEP ratios increased at POST for VM and RF muscles (P = 0.009 and P = 0.013, respectively) for both VIBtendon and VIBmuscle. CONCLUSION: The present results suggest that prolonged muscle and tendon LV are similarly effective in modulating central nervous system excitability and decreasing maximal force. Yet, altered explosive performance after tendon but not muscle LV suggests greater neural alterations when tendons are vibrated.

A Single Bout of Ultra-Endurance Exercise Reveals Early Signs of Muscle Aging in Master Athletes.

Middle-aged and master endurance athletes exhibit similar physical performance and long-term muscle adaptation to aerobic exercise. Nevertheless, we hypothesized that the short-term plasticity of the skeletal muscle might be distinctly altered for master athletes when they are challenged by a single bout of prolonged moderate-intensity exercise. Six middle-aged (37Y) and five older (50Y) master highly-trained athletes performed a 24-h treadmill run (24TR). Vastus lateralis muscle biopsies were collected before and after the run and assessed for proteomics, fiber morphometry, intramyocellular lipid droplets (LD), mitochondrial oxidative activity, extracellular matrix (ECM), and micro-vascularisation. Before 24TR, muscle fiber type morphometry, intramyocellular LD, oxidative activity, ECM and micro-vascularisation were similar between master and middle-aged runners. For 37Y runners, 24TR was associated with ECM thickening, increased capillary-to-fiber interface, and an 89% depletion of LD in type-I fibers. In contrast, for 50Y runners, 24TR did not alter ECM and capillarization and poorly depleted LDs. Moreover, an impaired succinate dehydrogenase activity and functional class scoring of proteomes suggested reduced oxidative phosphorylation post-24TR exclusively in 50Y muscle. Collectively, our data support that middle-aged and master endurance athletes exhibit distinct transient plasticity in response to a single bout of ultra-endurance exercise, which may constitute early signs of muscle aging for master athletes.

Beneficial effects of endurance exercise training on skeletal muscle microvasculature in sickle cell disease patients.

Sickle cell disease (SCD) is a genetic hemoglobinopathy leading to 2 major clinical manifestations: severe chronic hemolytic anemia and iterative vaso-occlusive crises. SCD is also accompanied by profound muscle microvascular remodeling. The beneficial effects of endurance training on microvasculature are widely known. The aim of this study was to evaluate the effects of an endurance training program on microvasculature of skeletal muscle in SCD patients. A biopsy of the vastus lateralis muscle and submaximal incremental exercise was performed before and after the training period. Of the 40 randomized SCD patients, complete data sets from 32 patients were obtained. The training group (n = 15) followed a personalized moderate-intensity endurance training program, while the nontraining (n = 17) group maintained a normal lifestyle. Training consisted of three 40-minute cycle ergometer exercise sessions per week for 8 weeks. Histological analysis highlighted microvascular benefits in the training SCD patients compared with nontraining patients, including increases in capillary density (P = .003), number of capillaries around a fiber (P = .015), and functional exchange surface (P < .0001). Conversely, no significant between-group difference was found in the morphology of capillaries. Indexes of physical ability also improved in the training patients. The moderate-intensity endurance exercise training program improved the muscle capillary network and partly reversed the microvascular defects commonly observed in skeletal muscle of SCD patients. This trial was registered at www.clinicaltrials.gov as #NCT02571088.

Is constitutional thinness really different from anorexia nervosa? A systematic review and meta-analysis.

A growing interest in constitutional thinness has been observed in the last decades, but the publications however cover various fields of study and report equivocal results. The present work systematically reviewed any clinical trials enrolling participants with constitutional thinness and bibliographic researches were performed between December 2018 and June 2020. From a total of 1 212 records initially identified, 402 records were removed as duplicates, 381 articles were excluded based on titles or abstracts and 390 references were excluded against eligibility criteria. Thirty-nine articles were finally included in the systematic review. The results showed that constitutionally thin people seem to be underweight but not underfat and present a fat-free mass as blunted as anorexic patients, despite being a little less underweight. The meta-analysis confirmed that constitutionally thin people present normal energy intake and revealed a trend toward a higher resting metabolic rate to fat-free mass ratio which suggests a highly metabolic fat-free mass. Contrary to patients with anorexia nervosa, constitutionally thin people present normal levels of insulin-like growth factor 1, estradiol, growth hormone, follicle-stimulating hormone, and luteinizing hormone. An intermediate level of leptin between anorexic and control participants was however observed in constitutional thinness. While all the studies reported normal free triiodothyronine and cortisol levels in constitutionally thin individuals, a higher fasting free triiodothyronine level (p = 0.033) and a lower 24 h mean cortisol level (p = 0.005) were observed for the first time. Present results give robust evidence that constitutionally thin people present an atypical phenotype highly different from anorexia nervosa.

Deep phenotyping of an international series of patients with late-onset dysferlinopathy.

BACKGROUND: To describe the clinical, pathological, and molecular characteristics of late-onset (LO) dysferlinopathy patients. METHODS: Retrospective series of patients with LO dysferlinopathy, defined by an age at onset of symptoms ≥30 years, from neuromuscular centers in France and the International Clinical Outcome Study for dysferlinopathy (COS). Patients with early-onset (EO) dysferlinopathy (<30 years) were randomly selected from the COS study as a control group, and the North Star Assessment for Dysferlinopathy (NSAD) and Activity Limitation (ACTIVLIM) scores were used to assess functionality. Muscle biopsies obtained from 11 LO and 11 EO patients were revisited. RESULTS: Forty-eight patients with LO dysferlinopathy were included (28 females). Median age at onset of symptoms was 37 (range 30-57) years and most patients showed a limb-girdle (n = 26) or distal (n = 10) phenotype. However, compared with EO dysferlinopathy patients (n = 48), LO patients more frequently showed atypical phenotypes (7 vs. 1; p = 0.014), including camptocormia, lower creatine kinase levels (2855 vs. 4394 U/L; p = 0.01), and higher NSAD (p = 0.008) and ACTIVLIM scores (p = 0.016). Loss of ambulation in LO patients tended to occur later (23 ± 4.4 years after disease onset vs. 16.3 ± 6.8 years; p = 0.064). Muscle biopsy of LO patients more frequently showed an atypical pattern (unspecific myopathic changes) as well as significantly less necrosis regeneration and inflammation. Although LO patients more frequently showed missense variants (39.8% vs. 23.9%; p = 0.021), no differences in dysferlin protein expression were found on Western blot. CONCLUSIONS: Late-onset dysferlinopathy patients show a higher frequency of atypical presentations, are less severely affected, and show milder dystrophic changes in muscle biopsy.

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.

Muscle Proteomic and Transcriptomic Profiling of Healthy Aging and Metabolic Syndrome in Men.

(1) Background: Aging is associated with a progressive decline in muscle mass and function. Aging is also a primary risk factor for metabolic syndrome, which further alters muscle metabolism. However, the molecular mechanisms involved remain to be clarified. Herein we performed omic profiling to decipher in muscle which dominating processes are associated with healthy aging and metabolic syndrome in old men. (2) Methods: This study included 15 healthy young, 15 healthy old, and 9 old men with metabolic syndrome. Old men were selected from a well-characterized cohort, and each vastus lateralis biopsy was used to combine global transcriptomic and proteomic analyses. (3) Results: Over-representation analysis of differentially expressed genes (ORA) and functional class scoring of pathways (FCS) indicated that healthy aging was mainly associated with upregulations of apoptosis and immune function and downregulations of glycolysis and protein catabolism. ORA and FCS indicated that with metabolic syndrome the dominating biological processes were upregulation of proteolysis and downregulation of oxidative phosphorylation. Proteomic profiling matched 586 muscle proteins between individuals. The proteome of healthy aging revealed modifications consistent with a fast-to-slow transition and downregulation of glycolysis. These transitions were reduced with metabolic syndrome, which was more associated with alterations in NADH/NAD+ shuttle and ß-oxidation. Proteomic profiling further showed that all old muscles overexpressed protein chaperones to preserve proteostasis and myofiber integrity. There was also evidence of aging-related increases in reactive oxygen species but better detoxifications of cytotoxic aldehydes and membrane protection in healthy than in metabolic syndrome muscles. (4) Conclusions: Most candidate proteins and mRNAs identified herein constitute putative muscle biomarkers of healthy aging and metabolic syndrome in old men.

Skeletal Ryanodine Receptors Are Involved in Impaired Myogenic Differentiation in Duchenne Muscular Dystrophy Patients.

Duchenne muscular dystrophy (DMD) is characterized by progressive muscle wasting following repeated muscle damage and inadequate regeneration. Impaired myogenesis and differentiation play a major role in DMD as well as intracellular calcium (Ca2+) mishandling. Ca2+ release from the sarcoplasmic reticulum is mostly mediated by the type 1 ryanodine receptor (RYR1) that is required for skeletal muscle differentiation in animals. The study objective was to determine whether altered RYR1-mediated Ca2+ release contributes to myogenic differentiation impairment in DMD patients. The comparison of primary cultured myoblasts from six boys with DMD and five healthy controls highlighted delayed myoblast differentiation in DMD. Silencing RYR1 expression using specific si-RNA in a healthy control induced a similar delayed differentiation. In DMD myotubes, resting intracellular Ca2+ concentration was increased, but RYR1-mediated Ca2+ release was not changed compared with control myotubes. Incubation with the RYR-calstabin interaction stabilizer S107 decreased resting Ca2+ concentration in DMD myotubes to control values and improved calstabin1 binding to the RYR1 complex. S107 also improved myogenic differentiation in DMD. Furthermore, intracellular Ca2+ concentration was correlated with endomysial fibrosis, which is the only myopathologic parameter associated with poor motor outcome in patients with DMD. This suggested a potential relationship between RYR1 dysfunction and motor impairment. Our study highlights RYR1-mediated Ca2+ leakage in human DMD myotubes and its key role in myogenic differentiation impairment. RYR1 stabilization may be an interesting adjunctive therapeutic strategy in DMD.

Two new reliable immunohistochemical methods for simultaneous identification of capillaries, the three types of fibers and basal lamina in human skeletal muscle.

Capillary network of skeletal muscle has a crucial role in oxygen supply and is strongly associated with the phenotype and metabolic profile of muscle fibers. Abundant literature has explored capillarization of skeletal muscle in different populations and in response to different interventions. Capillary and fiber type identification techniques have considerably evolved over the last decades, but to the best of our knowledge, no validated immunohistochemical method has yet been developed to simultaneously identify capillaries (using CD31), the three different muscle fiber types, and basal lamina. Nine human muscle biopsies of vastus lateralis were stained using 5 different methods to test: the reliability of different CD31 antibodies for capillary identification, the reliability between single-section or serial-section methods, and the intra-experimenter reproducibility in visual detection of capillaries. High reliability for the different antibodies directed against capillaries was observed for capillary contacts (CC) measurements (intra-class correlations (ICC) [ICC95%] of 0.89 [0.72; 0.96] for type I fibers, 0.93 [0.81; 0.97] for type IIA fibers, 0.88 [0.71; 0.96] for type IIX fibers, 0.95 [0.86; 0.98] for all fiber types) as well as a high level of similarity between single and serial sections methods. A strong similarity in capillary analysis between the different methods was obtained for each sample measurements. Analysis of Lin's concordance correlation coefficients and Bland and Altman's graphics showed a strong intra-experimenter reproducibility. This article proposes two time- and tissue-sparing immunohistochemical methods to accurately assess a complete fiber typing (type I, IIA, and IIX) along with muscle capillarization on a single muscle section.

Muscle structural, energetic and functional benefits of endurance exercise training in sickle cell disease.

Sickle cell disease (SCD) patients display skeletal muscle hypotrophy, altered oxidative capacity, exercise intolerance and poor quality of life. We previously demonstrated that moderate-intensity endurance training is beneficial for improving muscle function and quality of life of patients. The present study evaluated the effects of this moderate-intensity endurance training program on skeletal muscle structural and metabolic properties. Of the 40 randomized SCD patients, complete data sets were obtained from 33. The training group (n = 15) followed a personalized moderate-intensity endurance training program, while the non-training (n = 18) group maintained a normal lifestyle. Biopsies of the vastus lateralis muscle and submaximal incremental cycling tests were performed before and after the training program. Endurance training increased type I muscle fiber surface area (P = .038), oxidative enzyme activity [citrate synthase, P < .001; ß-hydroxyacyl-CoA dehydrogenase, P = .009; type-I fiber cytochrome c oxidase, P = .042; respiratory chain complex IV, P = .017] and contents of respiratory chain complexes I (P = .049), III (P = .005), IV (P = .003) and V (P = .002). Respiratory frequency, respiratory exchange ratio, blood lactate concentration and rating of perceived exertion were all lower at a given submaximal power output after training vs non-training group (all P < .05). The muscle content of proteins involved in glucose transport and pH regulation were unchanged in the training group relative to the non-training group. The moderate-intensity endurance exercise program improved exercise capacity and muscle structural and oxidative properties. This trial was registered at www.clinicaltrials.gov as #NCT02571088.

Non-oxidative Energy Supply Correlates with Lactate Transport and Removal in Trained Rowers.

This study aimed to test if the non-oxidative energy supply (estimated by the accumulated oxygen deficit) is associated with an index of muscle lactate accumulation during exercise, muscle monocarboxylate transporter content and the lactate removal ability during recovery in well-trained rowers. Seventeen rowers completed a 3-min all-out exercise on rowing ergometer to estimate the accumulated oxygen deficit. Blood lactate samples were collected during the subsequent passive recovery to assess individual blood lactate curves, which were fitted to the bi-exponential time function: La(t)= [La](0)+A1·(1-e-γ 1 t)+A2·(1-e-γ 2 t), where the velocity constants γ1 and γ2 (min-1) denote the lactate exchange and removal abilities during recovery, respectively. The accumulated oxygen deficit was correlated with the net amount of lactate released from the previously active muscles (r =0.58, P<0.05), the monocarboxylate transporters MCT1 and MCT4 (r=0.63, P<0.05) and γ2 (r=0.55, P<0.05). γ2 and the lactate release rate at exercise completion were negatively correlated with citrate synthase activity. These findings suggest that the capacity to supply non-oxidative energy during supramaximal rowing exercise is associated with muscle lactate accumulation and transport, as well as lactate removal ability.

Impact of Trail Running Races on Blood Viscosity and Its Determinants: Effects of Distance.

Blood rheology is a key determinant of tissue perfusion at rest and during exercise. The present study investigated the effects of race distance on hematological, blood rheological, and red blood cell (RBC) senescence parameters. Eleven runners participated in the Martigny-Combes à Chamonix 40 km race (MCC, elevation gain: 2300 m) and 12 others in the Ultra-Trail du Mont Blanc (UTMB, 171 km, elevation gain: 10,000 m). Blood samples were collected before and after the races. After the UTMB, the percentage of RBC phosphatidylserine (PS) exposure was not affected while RBC CD235a levels decreased and RBC-derived microparticles increased. In contrast, after the MCC, RBC PS exposure increased, while RBC CD235a and RBC-derived microparticles levels were not affected. The free hemoglobin and hemolysis rate did not change during the races. RBC aggregation and blood viscosity at moderate shear rates increased after the MCC. RBC deformability, blood viscosity at a high shear rate, and hematocrit decreased after the UTMB but not after the MCC. Our results indicate that blood rheology behavior is different between a 40 km and a 171 km mountain race. The low blood viscosity after the ultra-marathon might facilitate blood flow to the muscles and optimize aerobic performance.

Monosomy 18p is a risk factor for facioscapulohumeral dystrophy.

BACKGROUND: 18p deletion syndrome is a rare disorder caused by partial or full monosomy of the short arm of chromosome 18. Clinical symptoms caused by 18p hemizygosity include cognitive impairment, mild facial dysmorphism, strabismus and ptosis. Among other genes, structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHD1) is hemizygous in most patients with 18p deletions. Digenic inheritance of a SMCHD1 mutation and a moderately sized D4Z4 repeat on a facioscapulohumeral muscular dystrophy (FSHD) permissive genetic background of chromosome 4 can cause FSHD type 2 (FSHD2). OBJECTIVES: Since 12% of Caucasian individuals harbour moderately sized D4Z4 repeats on an FSHD permissive background, we tested if people with 18p deletions are at risk of developing FSHD. METHODS: To test our hypothesis we studied different cellular systems originating from individuals with 18p deletions not presenting FSHD2 phenotype for transcriptional and epigenetic characteristics of FSHD at D4Z4. Furthermore, individuals with an idiopathic muscle phenotype and an 18p deletion were subjected to neurological examination. RESULTS: Primary fibroblasts hemizygous for SMCHD1 have a D4Z4 chromatin structure comparable with FSHD2 concomitant with DUX4 expression after transdifferentiation into myocytes. Neurological examination of 18p deletion individuals from two independent families with a moderately sized D4Z4 repeat identified muscle features compatible with FSHD. CONCLUSIONS: 18p deletions leading to haploinsufficiency of SMCHD1, together with a moderately sized FSHD permissive D4Z4 allele, can associate with symptoms and molecular features of FSHD. We propose that patients with 18p deletion should be characterised for their D4Z4 repeat size and haplotype and monitored for clinical features of FSHD.

Evidence for a profound remodeling of skeletal muscle and its microvasculature in sickle cell anemia.

Sickle cell anemia (SCA) is a hemoglobinopathy leading to major hematologic, hemorheologic, and hemodynamic disorders that induce various complications, including organ failure, and ultimately lead to death. Here, we assessed for the first time repercussions of SCA on skeletal muscle and its microvasculature. Twenty-seven sedentary Cameroonian volunteer men participated in the study. They were assigned to one of three groups according to their hemoglobin status (healthy control subjects, n = 10; sickle cell trait carriers, n = 10; and SCA patients, n = 7) and underwent muscle biopsy of the vastus lateralis. SCA was associated with microvessel rarefaction, decrease in capillary tortuosity, and widening of microvessel diameter. The absence of capillary wall reinforcement was shown by lack of wall thickening and lack of fibrous tissue or smooth muscle in their constitution. We also observed changes in fiber type distribution, muscle atrophy, an increase in satellite cell number, and a decrease in activity of creatine kinase and several oxidative enzymes. No signs of tissue necrosis, inflammatory stress, fibrosis, or segmented fibers were observed. The present study highlighted marked effects of SCA on microvascular, structural, and energetic characteristics of skeletal muscle.