Although strenuous exercise may expose sickle cell disease (SCD) patients to risks of vaso-occlusive crisis, evidence suggests that regular endurance exercise may be beneficial. This study aimed to ...test (i) the safety and usefulness of a submaximal incremental exercise in evaluating physical ability of SCD patients and identify a marker for the management of endurance exercise and (ii) the feasibility of endurance exercise sessions in SCD patients.
Twenty adults with SCD (12 men and 8 women) performed a submaximal incremental exercise used to determine the first lactate threshold (LT1) and stopped as soon as blood lactate concentration (lactateb) reached ≥4 mmol·L. Fifteen of those patients (8 men and 7 women) also performed three 30-min endurance exercise sessions at ~2.5 mmol·L of lactateb on separate occasions.
LT1 occurred at 47 ± 3 and 33 ± 3 W for men and women, respectively, demonstrating the extreme deconditioning and, thus, low physical ability of adult SCD patients. During endurance exercise, peripheral oxygen saturation and lactateb most often remained stable and within acceptable ranges.
The proposed strategy of submaximal incremental exercise allowed safe determination of LT1, an important parameter of patients' physical ability. The study also demonstrated the feasibility and safety of individually tailored endurance exercises at ~2.5 mmol·L of lactateb. These latter results suggest that endurance training programs may be considered for adult SCD patients and that the method proposed here may be helpful in that regard.
Abstract This study aimed to evaluate the sex difference in active muscle stiffness of the tibialis anterior muscle (TA) through shear modulus measurements performed using supersonic shear imaging ...(SSI) technique. Twenty-five women and twenty-one men participated in this study. Joint torque, electromyographic (EMG) activity and shear modulus were measured during two sets of submaximal dorsiflexions performed at 20, 30, 40, 50 and 60% of maximal voluntary contraction (MVC) in a random order. The first set was devoted to the EMG recordings and the second set was devoted to the elastographic measurements. For each set, subjects performed three 5-s trials at each level of submaximal voluntary contraction. Stiffness indexes were calculated as the slopes of the linear regressions established between shear modulus and joint torque (SITORQUE ) or estimated TA EMG levels (SIEMG ). In the present study, no sex effect was reported for SITORQUE , SIEMG ( p =0.76 and p =0.86, respectively), and shear modulus measured at various contraction levels. The results highlight that men and women presented similar TA active stiffness indexes determined using SSI. Regardless of sex, this result suggests similar intrinsic stiffness for the contracting TA.
ABSTRACT
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.
Despite interest in the possibility of females outperforming males in ultraendurance sporting events, little is known about the sex differences in fatigue during prolonged locomotor exercise. This ...study investigated possible sex differences in central and peripheral fatigue in the knee extensors and plantar flexors resulting from a 110-km ultra-trail-running race.
Neuromuscular function of the knee extensors and plantar flexors was evaluated via transcranial magnetic stimulation (TMS) and electrical nerve stimulation before and after an ultra-trail-running race in 20 experienced ultraendurance trail runners (10 females and 10 males matched by percent of the winning time by sex) during maximal and submaximal voluntary contractions and in relaxed muscle.
Maximal voluntary knee extensor torque decreased more in males than in females (-38% vs -29%, P = 0.006) although the reduction in plantar flexor torque was similar between sexes (-26% vs -31%). Evoked mechanical plantar flexor responses decreased more in males than in females (-23% vs -8% for potentiated twitch amplitude, P = 0.010), indicating greater plantar flexor peripheral fatigue in males. Maximal voluntary activation assessed by TMS and electrical nerve stimulation decreased similarly in both sexes for both muscle groups. Indices of knee extensor peripheral fatigue and corticospinal excitability and inhibition changes were also similar for both sexes.
Females exhibited less peripheral fatigue in the plantar flexors than males did after a 110-km ultra-trail-running race and males demonstrated a greater decrease in maximal force loss in the knee extensors. There were no differences in the magnitude of central fatigue for either muscle group or TMS-induced outcomes. The lower level of fatigue in the knee extensors and peripheral fatigue in the plantar flexors could partly explain the reports of better performance in females in extreme duration running races as race distance increases.
The well-established central deficit in ultraendurance running races is not understood. The use of transcranial magnetic stimulation (TMS) in parallel with peripheral nerve stimulation provides ...insight into the source of these central changes. The aims of this study were to determine the presence and magnitude of voluntary activation deficits, especially supraspinal deficits, after a mountain trail-running race and to determine whether this can be explained by simultaneous changes in corticospinal excitability and intracortical inhibition.
Neuromuscular function (TMS and femoral nerve electrical stimulation) of the knee extensors was evaluated before and after a 110-km ultratrail in 25 experienced ultraendurance trail runners during maximal and submaximal voluntary contractions and in relaxed muscle.
Voluntary activation assessed by both femoral nerve electrical stimulation (-26%) and TMS (-16%) decreased and were correlated (P < 0.01). Decreases in potentiated twitch and doublet amplitudes were correlated with decreased voluntary activation assessed by TMS (P < 0.05). There was increased motor-evoked potential (MEP) amplitude (P < 0.05) without change in cortical silent period (CSP) elicited by TMS at optimal stimulus intensity. Conversely, CSP at suboptimal TMS intensity increased (P < 0.05) without concurrent change in MEP amplitude.
The present results demonstrate the development of a large central activation deficit assessed by TMS, indicating that cortical motoneurons are severely impaired in their ability to fire at optimal frequency or be fully recruited after an ultraendurance running race. MEP and CSP responses suggest a shift in the sigmoidal MEP-stimulus intensity relationship toward larger MEP at higher TMS intensity without change in inflection point of the curve and a left shift in the CSP-stimulus intensity relationship.
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.
Granulomatous myositis (GM) is a rare condition that has generally been described in association with sarcoidosis. In the absence of sarcoidosis or other underlying disease, a diagnosis of isolated ...GM is considered. Only one study has focused on the clinical difference between isolated GM and sarcoid myopathy (SM). We report 13 cases of symptomatic GM; 8 had sarcoidosis. All patients with sarcoidosis had predominantly proximal, symmetrical lower‐limb weakness, and 3 subsequently developed upper‐limb or distal involvement. Three of the five patients with isolated GM had predominantly distal muscle involvement, and two had dysphagia. Corticosteroid treatment was followed by prolonged improvement in only one patient with sarcoidosis. One patient had acute sarcoid myositis and benefited from methotrexate; other immunosuppressants and etanercept proved ineffective in chronic sarcoid myopathy. Three of the five patients with isolated GM responded to corticosteroid treatment. When last examined, three patients with sarcoidosis had severe disability, whereas patients with isolated GM showed milder weakness. Thus, SM was frequently associated with severe disability and rarely improved after corticosteroid treatment, whereas most patients with isolated GM improved. Muscle Nerve, 2006
In 2017, a new treatment by nusinersen, an antisense oligonucleotide delivered by repeated intrathecal injections, became available for patients with spinal muscular atrophy (SMA), whereas clinical ...trials had mainly involved children. Since 2020, the oral, selective SMN2-splicing modifier risdiplam has been available with restrictions evolving with time. In this peculiar context of lack of data regarding adult patients, many questions were raised to define the indications of treatment and the appropriate follow-up in this population. To homogenize access to treatment in France, a national multidisciplinary team meeting dedicated to adult SMA patients, named SMA multidisciplinary team meeting, (SMDTs) was created in 2018. Our objective was to analyze the value of SMDTs in the decision-making process in SMA adult patients and to provide guidelines about treatment.
From October 2020 to September 2021, data extracted from the SMDT reports were collected. The primary outcome was the percentage of cases in which recommendations on validating treatment plans were given. The secondary outcomes were type of treatment requested, description of expectations regarding treatment and description of recommendations or follow-up and discontinuation. Data were analyzed using descriptive statistics. Comparisons between the type of treatment requested were performed using Mann-Whitney test or the Student t test for quantitative data and the Fisher's exact test or the χ
test for qualitative data.
Cases of 107 patients were discussed at the SMDTs with a mean age of 35.3 (16-62). Forty-seven were SMA type 2, and 57 SMA type 3. Twelve cases were presented twice. Out of 122 presentations to the SMDTs, most of requests related to the initiation of a treatment (nusinersen (n = 46), risdiplam (n = 54), treatment without mentioning preferred choice (n = 5)) or a switch of treatment (n = 12). Risdiplam requests concerned significantly older patients (p = 0.002), mostly SMA type 2 (p < 0.0001), with greater disease severity in terms of motor and respiratory function compared to requests for nusinersen. In the year prior to presentation to the SMDTs, most of the patients experienced worsening of motor weakness assessed by functional tests as MFM32 or other meaningful scales for the most severe patients. Only 12% of the patients discussed had a stable condition. Only 49/122 patients (40.1%) expressed clear expectations regarding treatment. The treatment requested was approved by the SMDTs in 72 patients (67.2%). The most common reasons to decline treatment were lack of objective data on the disease course prior discussion to the SMDTs or inappropriate patient's expectations. Treatment requests were more likely to be validated by the SMDTs if sufficient pre-therapeutic functional assessment had been performed to assess the natural history (55% vs. 32%) and if the patient had worsening rather than stable motor function (p = 0.029). In patients with approved treatment, a-priori criteria to define a further ineffectiveness of treatment (usually after 14 months of treatment) were proposed for 67/72 patients.
In the context of costly treatments with few controlled studies in adults with SMA, in whom assessment of efficacy can be complex, SMDTs are 'real-world observatories' of great interest to establish national recommendations about indications of treatment and follow-up.
Exercise training (ExTr) is largely used to improve functional capacity in patients with chronic obstructive pulmonary disease (COPD). However, ExTr only partially restores muscle function in ...patients with COPD, suggesting that confounding factors may limit the efficiency of ExTr. In the present study, we hypothesized that skeletal muscle adaptations triggered by ExTr could be compromised in hypoxemic patients with COPD. Vastus lateralis muscle biopsies were obtained from patients with COPD who were either normoxemic (n = 15, resting arterial Po2 = 68.5 ± 1.5 mmHg) or hypoxemic (n = 8, resting arterial Po2 = 57.0 ± 1.0 mmHg) before and after a 2-mo ExTr program. ExTr induced a significant increase in exercise capacity both in normoxemic and hypoxemic patients with COPD. However, ExTr increased citrate synthase and lactate dehydrogenase enzyme activities only in skeletal muscle of normoxemic patients. Similarly, muscle fiber cross-sectional area and capillary-to-fiber ratio were increased only in patients who were normoxemic. Expression of atrogenes (MuRF1, MAFbx/Atrogin-1) and autophagy-related genes (Beclin, LC3, Bnip, Gabarapl) remained unchanged in both groups. Phosphorylation of Akt (Ser473), GSK-3β (Ser9), and p70S6k (Thr389) was nonsignificantly increased in normoxemic patients in response to ExTr, but it was significantly decreased in hypoxemic patients. We further showed on C2C12 myotubes that hypoxia completely prevented insulin-like growth factor-1-induced phosphorylation of Akt, GSK-3β, and p70S6K. Together, our observations suggest a role for hypoxemia in the adaptive response of skeletal muscle of patients with COPD in an ExTr program.
Objective
Facioscapulohumeral muscular dystrophy (FSHD) is linked to either contraction of D4Z4 repeats on chromosome 4 or to mutations in the SMCHD1 gene, both of which result in the aberrant ...expression of the transcription factor DUX4. However, it is still difficult to correlate these genotypes with the phenotypes observed in patients. Because we have recently shown that mice with disrupted Fat1 functions exhibit FSHD‐like phenotypes, we have investigated the expression of the human FAT1 gene in FSHD.
Methods
We first analyzed FAT1 expression in FSHD adult muscles and determined whether FAT1 expression was driven by DUX4. We next determined FAT1 expression levels in 64 muscles isolated from 16 control fetuses. These data were further complemented with analysis of Fat1 expression in developing mouse embryos.
Results
We demonstrated that FAT1 expression is independent of DUX4. Moreover, we observed that (1) in control fetal human biopsies or in developing mouse embryos, FAT1 is expressed at lower levels in muscles that are affected at early stages of FSHD progression than in muscles that are affected later or are nonaffected; and (2) in adult muscle biopsies, FAT1 expression is lower in FSHD muscles compared to control muscles.
Interpretation
We propose a revised model for FSHD in which FAT1 levels might play a role in determining which muscles will exhibit early and late disease onset, whereas DUX4 may worsen the muscle phenotype. Ann Neurol 2015;78:387–400
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