pinecone/core-2020-05-10-deduplication huggingface dataset:
A severe congenital myasthenic syndrome with "dropped head" caused by novel MUSK mutations

INTRODUCTION: Congenital myasthenic syndromes are rare. Mutations in MUSK were first described in 2004. Thirteen patients have been reported to date, mostly with a relatively mild course. The molecular diagnosis has implications for choice of treatment and genetic counseling.\ud
METHODS: Clinical course and electrophysiological, pathological, and genetic findings were assessed.\ud
RESULTS: We describe the case of a boy with prenatal onset and severe respiratory symptoms with a persisting need for ventilation. The patient had severe bulbar symptoms, marked axial weakness causing a "dropped head," and some facial and proximal weakness. Ophthalmoparesis developed during the first year of life. Salbutamol led to improvement, 3,4-diaminopyridine had a modest effect, but pyridostigmine produced deterioration. Two novel mutations in MUSK were found by whole exome sequencing.\ud
CONCLUSIONS: We expand the phenotype of congenital myasthenic syndromes with MUSK mutations, describing a more severe clinical course with prenatal onset. Predominant bulbar and respiratory weakness with facial and axial weakness and ophthalmoparesis are diagnostic clues
Magnetic stimulation supports muscle and nerve regeneration after trauma in mice

Magnetic stimulation (MS) has the ability to induce muscle twitch and has long been proposed as a therapeutic modality for skeletal muscle diseases. However, the molecular mechanisms underlying its means of action have not been defined.; Muscle regeneration after trauma was studied in a standard muscle injury mouse model. The influence of MS on the formation of motor units, posttrauma muscle/nerve regeneration, and vascularization was investigated.; We found that MS does not cause systemic or muscle damage but improves muscle regeneration by significantly minimizing the presence of inflammatory infiltrate and formation of scars after trauma. It avoids posttrauma muscle atrophy, induces muscle hypertrophy, and increases the metabolism and turnover of muscle. It triples the expression of muscle markers and significantly improves muscle functional recovery after trauma.; Our results indicate that MS supports muscle and nerve regeneration by activating muscle-nerve cross-talk and inducing the maturation of neuromuscular junctions. Muscle Nerve 53: 598-607, 2016
Peripheral and central fatigue after high intensity resistance circuit training

Introduction: The aim of this study was to investigate
the effects of high intensity resistance circuit (HIRC) and
traditional strength training (TST) on neuromuscular fatigue and
metabolic responses. Methods: Twelve trained young subjects
performed HIRC and TST in a counterbalanced order with 1
week rest in-between. The amount of workload and the interset
time for each local muscle group were matched (180 s),
however, the time between successive exercises differed. The
twitch interpolation technique was used to test neuromuscular
function of the knee extensor muscles. Blood lactate concentration
was used to evaluate metabolic responses. Results: Maximum
voluntary contraction and resting potentiated twitch
amplitude (Qtw) were significantly reduced after HIRC, but there
were not changes after TST, while reductions in voluntary activation
were similar. Lactate concentration increased significantly
more after HIRC. Conclusions: The higher lactate concentration
after HIRC probably impaired excitation-contraction coupling,
indicating larger peripheral fatigue than after TST.Actividad Física y Deport
Improvement in muscle strength with low-load isotonic training depends on fascicle length but not joint angle

Introduction: In this study we investigate whether low‐load isotonic training will elicit greater improvement in muscle strength at the same fascicle length, rather than at the same joint angle. Methods: Sixteen healthy men (24.1 ± 2.5 years of age) were randomly divided into intervention and control groups. Pre‐ and posttraining maximum isometric and isokinetic strengths and fascicle lengths of the medial gastrocnemius muscle were measured. Isotonic resistance training at 15 ° to 30 ° ankle plantarflexion at low intensity was conducted for 4 weeks. Results: The maximum isometric and isokinetic strength of the intervention group increased significantly only at 15 ° dorsiflexion and 8 ° to 12 ° dorsiflexion. Fascicle length during maximum voluntary contraction at 15 ° dorsiflexion to 0 ° was similar to fascicle length under training conditions. Discussion: It is possible that the improvement in muscle strength with low‐load training depends on fascicle length rather than joint angle
Combined xIL-6R and urocortin-2 treatment restores mdx diaphragm muscle force

Introduction: Duchenne muscular dystrophy (DMD) is characterized by progressive muscle degeneration leading to immobility, respiratory failure, and premature death. As chronic inflammation and stress are implicated in DMD pathology, the efficacy of an anti-inflammatory and anti-stress intervention strategy in ameliorating diaphragm dysfunction was investigated. Methods: Diaphragm muscle contractile function was compared in wild-type and dystrophin-deficient mdx mice treated with saline, anti-interleukin-6 receptor antibodies (xIL-6R), the corticotrophin-releasing factor receptor 2 (CRFR2) agonist, urocortin 2, or both xIL-6R and urocortin 2. Results: Combined treatment with xIL-6R and urocortin 2 rescued impaired force in mdx diaphragms. Mechanical work production and muscle shortening was also improved by combined drug treatment. Conclusions: Treatment which neutralizes peripheral IL-6 signaling and stimulates CRFR2 recovers force-generating capacity and the ability to perform mechanical work in mdx diaphragm muscle. These findings may be important in the search for therapeutic targets in DMD
An autopsy study of a familial oculopharyngeal muscular dystrophy (OPMD) with distal spread and neurogenic involvement

An 81-year-old man from a family with a history of oculopharyngeal muscular dystrophy (OPMD) involving 6 members over 4 generations is described. The patient first noted drooping of his eyelids at the age of 65. Dysphagia and dysarthria occurred soon thereafter. At age 78, impairment of gait developed and progressive wasting occurred in the limbs with an initial distal distribution. Electromyography of several limb muscles displayed a mixed myopathic and neurogenic pattern with giant potentials. Examination at autopsy revealed slight loss of neurons in the anterior horns of the spinal cord, with scanty ghost cells, neuronophagia, and central chromatolysis. By light microscopy the limb muscles showed moderate small-group atrophy with severe myopathy and target fibers. The viscerocranial muscles, including the ocular, vocal, and tongue muscles, demonstrated only myopathic change with the typical features of progressive muscular dystrophy. Advanced replacement by fibrous connective tissue and fat had occurred in both the viscerocranial and the lower limb muscles. The significance of neurogenic involvement in OPMD is discussed.
Adynamia episodica hereditaria with myotonia: A non-inactivating sodium current and the effect of extracellular pH

To study the mechanism of periodic paralysis, we investigated the properties of intact muscle fibers biopsied from a patient who had adynamia episodica hereditaria with electromyographic signs of myotonia. When the potassium concentration in the extracellular medium, [K]e, was 3.5 mmol/l, force of contraction, membrane resting potential, and intracellular sodium activity were normal, but depolarizing voltage clamp steps revealed the existence of an abnormal inward current. This current was activated at membrane potentials less negative than -80 mV, reached a maximum within 50 msec, and was not inactivated with time. The inward current was completely and reversibly blocked by tetrodotoxin, which indicates that it was carried by sodium ions. In a solution containing 9 mmol/l potassium, normal muscle would depolarize to -63 mV and yet be capable of developing full tetanic force upon stimulation. The muscle from the patient depolarized to -57 mV and became inexcitable, i.e., it was paralyzed. A contracture did not develop. Lowering of the extracellular pH did not influence the resting potential, but it effectively antagonized or prevented the paralytic effect of high [K]e by changing the inactivation characteristics of the sodium channels. Hydrochlorothiazide, which had a therapeutic effect on the patient, did not prevent paralysis in vitro. An abnormal rise of the intracellular sodium activity was recorded when the extracellular potassium concentration was raised to 10 mmol/l.
Enhancement of K+ conductance improves in vitro the contraction force of skeletal muscle in hypokalemic periodic paralysis

An abnormal ratio between Na+ and K+ conductances seems to be the cause for the depolarization and paralysis of skeletal muscle in primary hypokalemic periodic paralysis. Recently we have shown that the k+ channel opener cromakalim hyperpolarizes mammalian skeletal muscle fibers. Now we have studied the effects of this drug on the twitch force of muscle biopsies from normal and diseased human skeletal muscle. Cromakalim had little effect on the twitch force of normal muscle whereas it strongly improved the contraction force of fibers from patients suffering from hypokalemic periodic paralysis. Recordings of intracellular K+ and Cl- activities in human muscle and isolated rat soleus muscle support the view that cromakalim enhances the membrane K+ conductance (gK+). These data indicate that K+ channel openers may have a beneficial effect in primary hypokalemic periodic paralysis.
Restoration of conduction in the spinal roots correlates with clinical recovery from experimental autoimmune encephalomyelitis

In the Lewis rat, acute experimental autoimmune encephalomyelitis (EAE) induced by inoculation with myelin basic protein (MBP) and adjuvants is characterized by tail and hindlimb weakness that resolves spontaneously after several days. In rats with neurological signs of this form of EAE (MBP-EAE) we have previously demonstrated demyelination and nerve conduction block in the proximal peripheral nervous system (PNS) and in the central nervous system (CNS). The present study was performed to assess conduction in the PNS and CNS, after recovery from acute MBP-EAE, using direct recordings from surgically exposed spinal roots and spinal cord dorsal columns. The study revealed that 1-2 weeks after clinical recovery from tail paralysis there was almost complete restoration of conduction in the sacral spinal roots but persistent severe conduction abnormalities in the dorsal columns. Significant restoration of conduction through the dorsal columns occurred over the following 2 weeks. These findings indicate that PNS conduction block due to a demyelinating polyradiculitis is a major cause of the neurological signs of acute MBP-EAE in the Lewis rat
Glycogenosis type II (acid maltase deficiency)

Glycogen storage disease type II (GSD II/glycogenosis type II/Pompe's disease/acid maltase deficiency) is caused by the deficiency of lysosomal α-glucosidase resulting in lysosomal accumulation of glycogen. The disease is inherited as an autosomal recessive trait and is clinically heterogeneous. Early and late onset phenotypes are distinguished. Insight in the molecular nature of the lysosomal α-glucosidase deficiency and the underlying genetic defect has increased significantly during the past decade. This minireview on GSD II was written at the occasion of The International Symposium on Glycolytic and Mitochondrial Defects in Muscle and Nerve, held in Osaka, Japan, July 1994. It is an update of current literature, but also includes original data from the collaborating authors on mutations occurring in the lysosomal α-glucosidase gene and on prenatal diagnosis by chorionic villus sampling. The genotype–phenotype correlation and the prospects for therapy are addressed
Discussion of the paper: "Rock nail reinforcement of a free surface"

International audienceThe paper by Papamichos and Vardoulakis represents a contribution to the mechanical modelling of a rock material reinforced by the introduction of metallic bolts or nails, with a special emphasis on the way the interactions between the nails and the rock may be captured by means of a specific constitutive law. Leaving aside Section 2, which is devoted to the analysis of a single nail embedded in a rock specimen subject to plane-strain compression, our comments and criticisms will be focused on Section 3 (and secondarily Section 4), where the compression of a rectangular block of rock reinforced by an array of regularly distributed nails, is considered
Estimation of crack opening from a two-dimensional continuum-based finite element computation

Damage models are capable of representing crack initiation and mimicking crack propagation within a continuum framework. Thus, in principle, they do not describe crack openings. In durability analyses of concrete structures however, transfer properties are a key issue controlled by crack propagation and crack opening. We extend here a one dimensional approach for estimating a crack opening from a continuum based fi nite element calculation to two dimensional cases. The technique operates in the case of mode I cracking described in a continuum setting by a nonlocal isotropic damage model. We used the global tracking method to compute the idealized crack location as a post treatment procedure. The orig inal one dimensional problem devised in Dufour et al . [4] is recovered as pro fi les of deformation orthog onal to the idealized crack direction are computed. An estimate of the crack opening and an error indicator are computed by comparing fi nite element deformation pro fi les and theoretical pro fi les corresponding to a displacement discontinuity. Two estimates have been considered: In the strong approach, the maxima of the pro fi les are assumed to be equal; in the weak approach, the integrals of each pro fi le are set equal. Two dimensional numerical calculations show that the weak estimates perform better than do the strong ones. Error indicators, de fi ned as the distance between the numerical and theoretical pro fi les, are less than a few percentages. In the case of a three point bending, test results are in good agreement with experimental data, with an error lower than 10% for widely opened crack ( > 40 m m )Peer ReviewedPostprint (author's final draft
A finite element approach to the simulation of hydraulic fractures with lag

We presented a finite-element-based algorithm to simulate plane-strain, straight hydraulic fractures in an impermeable elastic medium. The algorithm acCOllllts for the nonlinear coupling between the fluid pressure and the crack opening and separately tracks the evolution of the crack tip and the fluid front. It therefore allows the existence of a fluid lag. The fluid front is advanced explicitly in time, but an implicit strategy is needed for the crack tip to guarantee the satisfaction of Griffith's criterion at each time step. We enforced the coupling between the fluid and the rock by simultaneously solving for the pressure field in the fluid and the crack opening at each time step. We provided verification of our algorithm by performing sample simulations and comparing them with two known similarity solutions.Peer ReviewedPostprint (author’s final draft
An approach to the modeling of viscoelastic damage. Application to the long-term creep of gypsum rock materials

International audienceA three-dimensional phenomenological model is developed to describe the long-term creep of gypsum rock materials. The approach is based on the framework of continuum damage mechanics where coupling with viscoelasticity is adopted. Specifically, a local damage model based on the concept of yield surface is proposed and deeply investigated. Among the many possibilities, we choose in this work its coupling with a generalized Kelvin-Voigt rheological model to formulate the whole behavior. Long-term as well as short-term relaxation processes can be integrated in the model by means of as many as necessary viscoelastic processes. The numerical discretization is described for an easy integration within a finite element procedure. Finally, a set of numerical simulations is given to show the possibilities of the presented model. It shows good agreement with some experimental results found in the literature
Modelling of steady-state fluid flow in 3D fractured isotropic porous media: Application to effective permeability calculation

International audienceIn this paper, 3D steady-state fluid flow in a porous medium with many intersecting fractures is derived numerically by using collocation method. Fluid flow, in the matrix and fractures, are described by Darcy's law and Poisseuille's law, respectively. The recent theoretical development presented a general potential solution to model the steady-state flow in fractured porous media under a far-field condition. This solution is a hypersingular integral equation with pressure field in the fracture surfaces as the main unknown. The numerical procedure can resolve the problem for any form of fractures and also takes into account the interactions and the intersection between fractures. Once the pressure field, and then the flux field in fractures have been determined, the pressure field in the porous matrix is computed completely. The basic problem of a single fracture is investigated and a semi-analytical solution is presented. Using the solution obtained for a single fracture, Mori-Tanaka and self-consistent schemes are employed for upscalling the effective permeability of 3D fractured porous media
Thermal recovery from a fractured medium in local thermal non‐equilibrium

International audienceThermal recovery from a hot dry rock (HDR) reservoir viewed as a deformable fractured medium is investigated with a focus on the assumption of local thermal non-equilibrium (LTNE). Hydraulic diffusion, thermal diffusion, forced convection and deformation are considered in a two-phase framework, the solid phase being made by impermeable solid blocks separated by saturated fractures. The finite element approximation of the constitutive and field equations is formulated and applied to obtain the response of a generic HDR reservoir to circulation tests. A change of time profile of the outlet fluid temperature is observed as the fracture spacing increases, switching from a single-step pattern to a double-step pattern, a feature which is viewed as characteristic of established LTNE. A dimensionless number is proposed to delineate between local thermal equilibrium (LTE) and non-equilibrium. This number embodies local physical properties of the mixture, elements of the geometry of the reservoir and the production flow rate. All the above properties being fixed, the resulting fracture spacing threshold between LTNE and LTE is found to decrease with increasing porosity or fluid velocity. The thermally induced effective stress is tensile near the injection well, illustrating the thermal contraction of the rock, while the pressure contribution of the fracture fluid is negligible during the late period
Simulation of long-term consolidation behavior of soft sensitive clay using an elasto-viscoplastic constitutive model

The phenomenon of excess pore water pressure increase or stagnation and continuing large ground deformation in soft sensitive clay following the completion of construction of embankment is simulated for a case study at Saint Alban, Quebec, Canada. The present model employs an updated Lagrangian finite element framework and is combined with an automatic time increment selection scheme. The simulation based on an elasto-viscoplastic constitutive model considers soil-structure degradation effect. It is shown that without consideration for the microstructural degradation effect, it is not possible to reproduce the field responses of soft sensitive clay even during the construction of the embankment. When the soil-structure degradation effect is considered, the present model can offer reasonably accurate prediction for the consolidation behavior of soft sensitive clay, including the so-called anomalous pore water pressure generation and continuing large deformation even after the end of construction, which has been posing numerous uncertainties on the long-term performance of earth structures
A homogenization approach for evaluating the longitudinal shear stiffness of reinforced soils: column versus cross trench configuration

International audienceThe macroscopic linear elastic behaviour of inclusion reinforced soils, regarded as periodic composite media, is investigated by means of the homogenization theory. Special attention is given here to the determination of their longitudinal shear stiffness properties, which strongly govern the reinforced ground response under lateral loading. Combining the use of analytical, variational as well as numerical methods, three particular engineering relevant configurations are more thoroughly examined: single trench, column and cross trench reinforcements. Fairly accurate closed-form expressions are thus obtained giving the value of the reinforced soil longitudinal shear stiffness as a function of the individual components shear moduli and reinforcement volume fraction. It is shown in particular that adopting a cross trench reinforcement layout instead of the classical column configuration results in a much higher improvement of the longitudinal shear stiffness. The results are then applied to assessing the reduction of soil liquefaction risk which can be attributed to the presence of the reinforcing inclusions. Again, they clearly demonstrate the excellent performance of the cross trench configuration as compared to the complete inefficiency of the column reinforcement technique
Granite rock fragmentation at percussive drilling - experimental and numerical investigation

International audienceThe aim of this study is to numerically model the fracture system at percussive drilling. Due to the complex behavior of rock materials, a continuum approach is employed relying upon a plasticity model with yield surface locus as a quadratic function of the mean pressure in the principal stress space coupled with an anisotropic damage model. In particular, Bohus granite rock is investigated and the material parameters are defined based on previous experiments. This includes different tests such as direct tension and compression, three point bending and quasi-oedometric tests to investigate the material behavior at both tension and confined compression stress states. The equation of motion is discretized using a FE approach and the explicit time integration method is employed. EOI (Edge-On Impact) tests are performed and the results are used to validate the numerical model. The percussive drilling problem is then modeled in 3D and the bit-rock interaction is considered using contact mechanics. The fracture mechanism in the rock and the bit penetration- resisting force response are realistically captured by the numerical model