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  1. Muscular Dystrophy

    MedlinePlus

    ... depending on the type of muscular dystrophy. Duchenne muscular dystrophy About half of people with muscular dystrophy have ... muscles Muscle pain and stiffness Learning disabilities Becker muscular dystrophy Signs and symptoms are similar to those of ...

  2. Muscular Dystrophy

    MedlinePlus

    ... Devices The Search for a Cure en español Distrofia muscular About MD Muscular dystrophy (MD) is a ... muscles and cause different degrees of muscle weakness. Duchenne muscular dystrophy is the most common and the ...

  3. Muscular Dystrophy

    MedlinePlus

    ... It Like for Teens With MD? en español Distrofia muscular Aside from seeing the telethon on Labor ... which weakens different muscle groups in various ways: Duchenne (pronounced: due-SHEN) muscular dystrophy (DMD) , the most ...

  4. Muscular Dystrophy

    MedlinePlus

    Muscular dystrophy (MD) is a group of more than 30 inherited diseases. They all cause muscle weakness and ... ability to walk. There is no cure for muscular dystrophy. Treatments can help with the symptoms and prevent ...

  5. Muscular dystrophy

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/001190.htm Muscular dystrophy To use the sharing features on this page, please enable JavaScript. Muscular dystrophy is a group of inherited disorders that cause ...

  6. Muscular Dystrophy

    MedlinePlus

    ... in Duchenne muscular dystrophy. Dev. Med. Child Neurol. Mar 1995;37(3):260-269. 4. Centers for ... DM1) . The International Myotonic Dystrophy Consortium (IDMC). Neurology. Mar 28 2000;54(6):1218-1221. 5. Harper ...

  7. Muscular Dystrophy

    MedlinePlus

    ... affects about 1 out of every 3,500 boys. (Girls can carry the gene that causes the disease, ... and heart problems. Limb-girdle muscular dystrophy affects boys and girls equally. Symptoms usually start when kids are between ...

  8. Muscular Dystrophy

    MedlinePlus

    ... be affected. Limb-girdle muscular dystrophy (LGMD) affects boys and girls equally, weakening muscles in the shoulders and upper ... weakness and poor muscle tone. Occurring in both girls and boys, it can have different symptoms. It varies in ...

  9. Muscular dystrophy - resources

    MedlinePlus

    Resources - muscular dystrophy ... The following organizations are good resources for information on muscular dystrophy : Muscular Dystrophy Association -- www.mdausa.org National Institute of Neurological Disorders and Stroke -- www.ninds.nih. ...

  10. Meaning of Muscular Dystrophy

    MedlinePlus

    ... Video: Getting an X-ray The Meaning of Muscular Dystrophy KidsHealth > For Kids > The Meaning of Muscular Dystrophy ... you know someone who has MD. What Is Muscular Dystrophy? Muscular dystrophy (say: MUS-kyoo-lur DIS-troh- ...

  11. Flexibility and Muscular Strength.

    ERIC Educational Resources Information Center

    Liemohn, Wendell

    1988-01-01

    This definition of flexibility and muscular strength also explores their roles in overall physical fitness and focuses on how increased flexibility and muscular strength can help decrease or eliminate lower back pain. (CB)

  12. Becker muscular dystrophy

    MedlinePlus

    ... and wheelchairs may improve movement and self-care. Genetic counseling may be recommended. Daughters of a man with ... Genetic counseling may be advised if there is a family history of Becker muscular dystrophy.

  13. Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Registry

    ClinicalTrials.gov

    2016-08-26

    Myotonic Dystrophy; Facioscapulohumeral Muscular Dystrophy; Muscular Dystrophy; Myotonic Dystrophy Type 1; Myotonic Dystrophy Type 2; Congenital Myotonic Dystrophy; PROMM (Proximal Myotonic Myopathy); Steinert's Disease; Myotonic Muscular Dystrophy

  14. Evaluation of Limb-Girdle Muscular Dystrophy

    ClinicalTrials.gov

    2014-03-06

    Becker Muscular Dystrophy; Limb-Girdle Muscular Dystrophy, Type 2A (Calpain-3 Deficiency); Limb-Girdle Muscular Dystrophy, Type 2B (Miyoshi Myopathy, Dysferlin Deficiency); Limb-Girdle Muscular Dystrophy, Type 2I (FKRP-deficiency)

  15. Learning about Duchenne Muscular Dystrophy

    MedlinePlus

    ... form of muscular dystrophy that occurs primarily in boys. It is caused by an alteration (mutation) in ... to date, which encodes the muscle protein, dystrophin. Boys with Duchenne muscular dystrophy do not make the ...

  16. Duchenne muscular dystrophy.

    PubMed

    Yiu, Eppie M; Kornberg, Andrew J

    2015-08-01

    Duchenne muscular dystrophy, an X-linked disorder, has an incidence of one in 5000 boys and presents in early childhood with proximal muscle weakness. Untreated boys become wheelchair bound by the age of 12 years and die of cardiorespiratory complications in their late teens to early 20s. The use of corticosteroids, non-invasive respiratory support, and active surveillance and management of associated complications have improved ambulation, function, quality of life and life expectancy. The clinical features, investigations and management of Duchenne muscular dystrophy are reviewed, as well as the latest in some of the novel therapies.

  17. Facioscapulohumeral muscular dystrophy.

    PubMed

    Statland, Jeffrey; Tawil, Rabi

    2014-08-01

    Facioscapulohumeral muscular dystrophy (FSHD) is a common type of adult muscular dystrophy and is divided into types 1 and 2 based on genetic mutation. Clinically, both FSHD types often show asymmetric and progressive muscle weakness affecting initially the face, shoulder, and arms followed by the distal then proximal lower extremities. Approximately 95% of patients, termed FSHD1, have a deletion of a key number of repetitive elements on chromosome 4q35. The remaining 5%, termed FSHD2, have no deletion on chromosome 4q35. Nevertheless, both types share a common downstream mechanism, making it possible for future disease-directed therapies to be effective for both FSHD types.

  18. Meaning of Muscular Dystrophy

    MedlinePlus

    ... MD Living With MD en español Qué significa distrofia muscular Over Labor Day, just as you're ... grown-up. This article talks about two types: Duchenne and Becker MD. Generally, only boys get Duchenne ...

  19. Spinal Muscular Atrophy (SMA)

    MedlinePlus

    ... Lessons? Visit KidsHealth in the Classroom What Other Parents Are Reading Your Child's Development (Birth to 3 Years) Feeding Your 1- to 3-Month-Old Feeding Your 4- to 7-Month-Old Feeding Your 8- to 12-Month-Old Feeding Your 1- to 2-Year-Old Spinal ... > For Parents > Spinal Muscular Atrophy (SMA) Print A A A ...

  20. Facioscapulohumeral muscular dystrophy.

    PubMed

    Tawil, Rabi

    2008-10-01

    Facioscapulohumeral muscular dystrophy (FSHD), a dominantly inherited disorder, is the third most common dystrophy after Duchenne and myotonic muscular dystrophy. No known effective treatments exist for FSHD. The lack of an understanding of the underlying pathophysiology remains an obstacle in the development of targeted therapeutic interventions. The genetic defect is a loss of a critical number of a repetitive element (D4Z4) in the 4q subtelomeric region. The loss of the repeats results in specific changes in chromatin structure, although neither the molecular nor the cellular consequences of this change are known. Nevertheless, these epigenetic changes in chromatin structure offer a potential therapeutic target. This review discusses current management strategies in FSHD as well as potential therapeutic interventions to slow down or reverse the progressive muscle atrophy and weakness.

  1. Translational Research for Muscular Dystrophy

    DTIC Science & Technology

    2012-05-01

    REPORT TYPE Annual 3. DATES COVERED 1 MAR 2011 - 30 APR 2012 4. TITLE AND SUBTITLE Translational Research for Muscular Dystrophy 5a. CONTRACT...SUPPLEMENTARY NOTES 14. ABSTRACT The goal of this work is to increase the availability of critical mouse models of human muscular dystrophy (MD...3 W81XWH-11-1-0330 Cox, Gregory A 4 4 11 11 12 Translational Research for Muscular Dystrophy W81XWH-11-1-0330 Gregory A

  2. Cardio-Muscular Conditioner

    NASA Technical Reports Server (NTRS)

    1993-01-01

    In the mid-sixties, Gary Graham, a Boeing designer, developed a cardiovascular conditioner for a planned Air Force orbiting laboratory. After the project was cancelled, Graham participated in space station conditioning studies for the Skylab program. Twenty years later, he used this expertise to develop the Shuttle 2000-1, a physical therapy and athletic development conditioner, available through Contemporary Designs. The machine is used by football teams, sports clinics and medical rehabilitation centers. Cardiovascular fitness and muscular strength development are promoted through both kinetic and plyometric exercises.

  3. Therapeutic advances in muscular dystrophy

    PubMed Central

    Leung, Doris G; Wagner, Kathryn R

    2013-01-01

    The muscular dystrophies comprise a heterogeneous group of genetic disorders that produce progressive skeletal muscle weakness and wasting. There has been rapid growth and change in our understanding of these disorders in recent years, and advances in basic science are being translated into increasing numbers of clinical trials. This review will discuss therapeutic developments in 3 of the most common forms of muscular dystrophy: Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, and myotonic dystrophy. Each of these disorders represents a different class of genetic disease (monogenic, epigenetic, and repeat expansion disorders), and the approach to therapy addresses the diverse and complex molecular mechanisms involved in these diseases. The large number of novel pharmacologic agents in development with good biologic rationale and strong proof of concept suggests there will be an improved quality of life for individuals with muscular dystrophy. PMID:23939629

  4. Retinal AO OCT

    NASA Astrophysics Data System (ADS)

    Zawadzki, Robert J.; Miller, Donald T.

    The last two decades have witnessed extraordinary advances in optical technology to image noninvasively and at high resolution the posterior segment of the eye. Two of the most impactful technological advancements over this period have arguably been optical coherence tomography (OCT) and adaptive optics (AO). The strengths of these technologies complement each other and when combined have been shown to provide unprecedented, micron-scale resolution (<3 μm) in all three dimensions and sensitivity to image the cellular retina in the living eye. This powerful extension of OCT, that is AO-OCT, is the focus of this chapter. It presents key aspects of designing and implementing AO-OCT systems. Particular attention is devoted to the relevant optical properties of the eye that ultimately define these systems, AO componentry and operation tailored for ophthalmic use, and of course use of the latest technologies and methods in OCT for ocular imaging. It surveys the wide range of AO-OCT designs that have been developed for retinal imaging, with AO integrated into every major OCT design configuration. Finally, it reviews the scientific and clinical studies reported to date that show the exciting potential of AO-OCT to image the microscopic retina and fundus in ways not previously possible with other noninvasive methods and a look to future developments in this rapidly growing field.

  5. Wasting Mechanisms in Muscular Dystrophy

    PubMed Central

    Shin, Jonghyun; Tajrishi, Marjan M.; Ogura, Yuji; Kumar, Ashok

    2013-01-01

    Muscular dystrophy is a group of more than 30 different clinical genetic disorders that are characterized by progressive skeletal muscle wasting and degeneration. Primary deficiency of specific extracellular matrix, sarcoplasmic, cytoskeletal, or nuclear membrane protein results in several secondary changes such as sarcolemmal instability, calcium influx, fiber necrosis, oxidative stress, inflammatory response, breakdown of extracellular matrix, and eventually fibrosis which leads to loss of ambulance and cardiac and respiratory failure. A number of molecular processes have now been identified which hasten disease progression in human patients and animal models of muscular dystrophy. Accumulating evidence further suggests that aberrant activation of several signaling pathways aggravate pathological cascades in dystrophic muscle. Although replacement of defective gene with wild-type is paramount to cure, management of secondary pathological changes has enormous potential to improving the quality of life and extending lifespan of muscular dystrophy patients. In this article, we have reviewed major cellular and molecular mechanisms leading to muscle wasting in muscular dystrophy. PMID:23669245

  6. Ageing with Muscular Disease

    PubMed Central

    Martinsen, Bente; Dreyer, Pia

    2016-01-01

    Background: The demographic development with an ageing population is predicted to be the next global public health challenge. Advances in medicine and the socioeconomic development have reduced mortality and morbidity due to infectious conditions and non-communicable diseases. The increase in longevity will not be restricted to healthy people. Objective: To understand how people with muscular diseases experience ageing. Method: A literature review was conducted using the Matrix Method developed by Garrard (2007). This systematic method was used to identify, describe and interpret studies, irrespective of the methods applied. To avoid the exclusion of important sources, experiences and topics, we chose an integrative approach that accommodates the inclusion of studies with different methodologies. People with MD have gradually extended their life expectancy during the last 30 years. Thus, we reviewed the literature regarding MD and ageing without time limit. Results: We identified three themes: 1) Slowing down early 2) Accepting lifelong deterioration and 3) Striving for normality. Conclusion: People with MD live in a field of tension between a feeling of autonomy and normality and difficulties coping with reduced physical abilities. Getting older accentuates this tension since the physical strength diminishes and it is harder to maintain autonomy. The bodily challenges may coincide with the end of the rehabilitation people living with MD have received. Seemingly, no age-related rehabilitation is offered, and people living with MD are thus at risk of an unnecessarily passive life. PMID:28144383

  7. Bed Rest Muscular Atrophy

    NASA Technical Reports Server (NTRS)

    Greenleaf, John E.

    2000-01-01

    A major debilitating response from prolonged bed rest (BR) is muscle atrophy, defined as a "decrease in size of a part of tissue after full development has been attained: a wasting away of tissue as from disuse, old age, injury or disease". Part of the complicated mechanism for the dizziness, increased body instability, and exaggerated gait in patients who arise immediately after BR may be a result of not only foot pain, but also of muscular atrophy and associated reduction in lower limb strength. Also, there seems to be a close association between muscle atrophy and bone atrophy. A discussion of many facets of the total BR homeostatic syndrome has been published. The old adage that use determines form which promotes function of bone (Wolff's law) also applies to those people exposed to prolonged BR (without exercise training) in whom muscle atrophy is a consistent finding. An extreme case involved a 16-year-old boy who was ordered to bed by his mother in 1932: after 50 years in bed he had "a lily-white frame with limbs as thin as the legs of a ladder-back chair". These findings emphasize the close relationship between muscle atrophy and bone atrophy. In addition to loss of muscle mass during deconditioning, there is a significant loss of muscle strength and a decrease in protein synthesis. Because the decreases in force (strength) are proportionately greater than those in fiber size or muscle cross-sectional area, other contributory factors must be involved; muscle fiber dehydration may be important.

  8. Muscular dystrophy in a dog resembling human becker muscular dystrophy.

    PubMed

    Baroncelli, A B; Abellonio, F; Pagano, T B; Esposito, I; Peirone, B; Papparella, S; Paciello, O

    2014-05-01

    A 3-year-old, male Labrador retriever dog was presented with clinical signs of progressive exercise intolerance, bilateral elbow extension, rigidity of the forelimbs, hindlimb flexion and kyphosis. Microscopical examination of muscle tissue showed marked variability in myofibre size, replacement of muscle with mature adipose tissue and degeneration/regeneration of muscle fibres, consistent with muscular dystrophy. Immunohistochemical examination for dystrophin showed markedly reduced labelling with monoclonal antibodies specific for the rod domain and the carboxy-terminal of dystrophin, while expression of β-sarcoglycan, γ-sarcoglycan and β-dystroglycan was normal. Immunoblotting revealed a truncated dystrophin protein of approximately 135 kDa. These findings supported a diagnosis of congenital canine muscular dystrophy resembling Becker muscular dystrophy in man.

  9. Spinal muscular atrophy

    PubMed Central

    2011-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle weakness and paralysis. Estimated incidence is 1 in 6,000 to 1 in 10,000 live births and carrier frequency of 1/40-1/60. This disease is characterized by generalized muscle weakness and atrophy predominating in proximal limb muscles, and phenotype is classified into four grades of severity (SMA I, SMAII, SMAIII, SMA IV) based on age of onset and motor function achieved. This disease is caused by homozygous mutations of the survival motor neuron 1 (SMN1) gene, and the diagnostic test demonstrates in most patients the homozygous deletion of the SMN1 gene, generally showing the absence of SMN1 exon 7. The test achieves up to 95% sensitivity and nearly 100% specificity. Differential diagnosis should be considered with other neuromuscular disorders which are not associated with increased CK manifesting as infantile hypotonia or as limb girdle weakness starting later in life. Considering the high carrier frequency, carrier testing is requested by siblings of patients or of parents of SMA children and are aimed at gaining information that may help with reproductive planning. Individuals at risk should be tested first and, in case of testing positive, the partner should be then analyzed. It is recommended that in case of a request on carrier testing on siblings of an affected SMA infant, a detailed neurological examination should be done and consideration given doing the direct test to exclude SMA. Prenatal diagnosis should be offered to couples who have previously had a child affected with SMA (recurrence risk 25%). The role of follow-up coordination has to be managed by an expert in neuromuscular disorders and in SMA who is able to plan a multidisciplinary intervention that includes pulmonary, gastroenterology/nutrition, and orthopedic care. Prognosis depends on the phenotypic

  10. Porcine models of muscular dystrophy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Duchenne muscular dystrophy is a progressive, fatal, X-linked disease caused by a failure to accumulate the cytoskeletal protein, dystrophin. This disease is modeled by a variety of animal models including several fish models, mice, rats, and dogs. While these models have contributed substantially t...

  11. Learning about Spinal Muscular Atrophy

    MedlinePlus

    ... causes the disorder. Top of page NHGRI Clinical Research on Spinal Muscular Atrophy Currently, NHGRI is not conducting studies on SMA. The National Institutes of Health is conducting clinical trials identified as enrolling individuals with SMA: Quantitative Analysis of SMN1 and SMN2 Gene Based on ...

  12. Wasting mechanisms in muscular dystrophy.

    PubMed

    Shin, Jonghyun; Tajrishi, Marjan M; Ogura, Yuji; Kumar, Ashok

    2013-10-01

    Muscular dystrophy is a group of more than 30 different clinical genetic disorders that are characterized by progressive skeletal muscle wasting and degeneration. Primary deficiency of specific extracellular matrix, sarcoplasmic, cytoskeletal, or nuclear membrane protein results in several secondary changes such as sarcolemmal instability, calcium influx, fiber necrosis, oxidative stress, inflammatory response, breakdown of extracellular matrix, and eventually fibrosis which leads to loss of ambulance and cardiac and respiratory failure. A number of molecular processes have now been identified which hasten disease progression in human patients and animal models of muscular dystrophy. Accumulating evidence further suggests that aberrant activation of several signaling pathways aggravate pathological cascades in dystrophic muscle. Although replacement of defective gene with wild-type is paramount to cure, management of secondary pathological changes has enormous potential to improving the quality of life and extending lifespan of muscular dystrophy patients. In this article, we have reviewed major cellular and molecular mechanisms leading to muscle wasting in muscular dystrophy. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.

  13. Chronic spinal muscular atrophy of facioscapulohumeral type.

    PubMed Central

    Furukawa, T; Toyokura, Y

    1976-01-01

    Chronic spinal muscular atrophy of FSH type affecting a mother and her son and daughter is reported. The relevant literature is reviewed and the relation between this conditon and Kugelberg-Welander (K-W) disease is discussed. Chronic spinal muscular atrophy of FSH type is considered to be a different entity from the eponymous K-W disease. Each type of muscular dystrophy, e.g. limb-girdle, FSH, distal, ocular, or oculopharyngeal type, has its counterpart of nuclear origin. A classification of the chronic spinal muscular atrophies is suggested following the classification of muscular dystrophy. Images PMID:957378

  14. Phase 3 Study of Ataluren in Patients With Nonsense Mutation Duchenne Muscular Dystrophy

    ClinicalTrials.gov

    2016-08-02

    Muscular Dystrophy, Duchenne; Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn

  15. AO Group Annual Report

    SciTech Connect

    Olivier, S

    2005-10-04

    The Adaptive Optics (AO) Group in I Division develops and tests a broad range of advanced wavefront control technologies. Current applications focus on: Remote sensing, High power lasers, Astronomy, and Human vision. In the area of remote sensing, the AO Group leads a collaborative effort with LLNL's Nonproliferation, Arms Control & International Security (NAI) Directorate on Enhanced Surveillance Imaging. The ability to detect and identify individual people or vehicles from long-range is an important requirement for proliferation detection and homeland security. High-resolution imaging along horizontal paths through the atmosphere is limited by turbulence, which blurs and distorts the image. For ranges over {approx}one km, visible image resolution can be reduced by over an order of magnitude. We have developed an approach based on speckle imaging that can correct the turbulence-induced blurring and provide high resolution imagery. The system records a series of short exposure images which freeze the atmospheric effects. We can then estimate the image magnitude and phase using a bispectral estimation algorithm which cancels the atmospheric effects while maintaining object information at the diffraction limit of the imaging system.

  16. [Fractures in spinal muscular atrophy].

    PubMed

    Febrer, Anna; Vigo, Meritxell; Rodríguez, Natalia; Medina, Julita; Colomer, Jaume; Nascimento, Andrés

    2013-09-01

    Objetivo. Determinar la frecuencia de fracturas en pacientes con atrofia muscular espinal, mecanismo de produccion, edad de aparicion y repercusion funcional. Pacientes y metodos. Se estudian 65 pacientes con atrofia muscular espinal. Se recogen las fracturas diagnosticadas mediante radiografia y se analizan los siguientes parametros: tipo de atrofia muscular espinal, marcha, edad en el momento de la fractura, mecanismo de produccion, localizacion, tratamiento aplicado y repercusion funcional. Resultados. Presentaron fracturas 13 pacientes (20%), con un total de 20 (cuatro presentaron dos o mas fracturas). La edad media fue de 6,35 años. La localizacion fue en su mayoria en el femur y el mecanismo de produccion, en 12 casos por caidas y en 8 por traumatismo menor. No detectamos ninguna fractura vertebral. Todas se trataron de manera conservadora. El unico paciente ambulante que presento una fractura dejo de caminar despues de la inmovilizacion. Conclusiones. La existencia de fracturas en estos pacientes interfiere en su calidad de vida y en el nivel funcional. Es importante la prevencion de las mismas en el manejo del paciente y vigilando la correcta postura en la silla de ruedas con sistemas de sujecion Deberian emprenderse mas estudios sobre la perdida de densidad mineral osea en estos pacientes y su posible relacion con las fracturas.

  17. Age-Related Differences in Muscular Strength and Muscular Endurance among Female Masters Swimmers.

    ERIC Educational Resources Information Center

    Dummer, Gail M.; And Others

    1985-01-01

    This study investigated age-related differences in muscular strength and muscular endurance among 73 female masters swimmers aged 24 to 71 years. While an age-related decline in muscular strength was apparent, the results failed to reveal a similar trend for endurance, suggesting that swimming influences endurance more than strength among women.…

  18. Validity of Field Tests of Upper Body Muscular Strength.

    ERIC Educational Resources Information Center

    Pate, Russell, R; And Others

    1993-01-01

    Examined the validity of field tests of elementary students' upper body muscular strength and endurance. Field tests were found to be moderately valid measures of weight-relative muscular strength but not of absolute strength and muscular endurance. (SM)

  19. Translational Research for Muscular Dystrophy

    DTIC Science & Technology

    2014-05-01

    JAX stock 18018: B10ScSn.Cg-Prkdcscid Dmdmdx/J Like human patients who suffer from one of the most common neuromuscular diseases, Duchenne muscular...overt phenotype in BL10.mdx mice. However, the muscle wasting and kyphosis of the D2.mdx mouse is evident at this early adult age. Figure 3...and whe antitative is a very e. Our atic loss X mice train at any re shown ness is total force per eakness ch earlier in, the of

  20. Nutrition Considerations in Duchenne Muscular Dystrophy.

    PubMed

    Davis, Jillian; Samuels, Emily; Mullins, Lucille

    2015-08-01

    Duchenne muscular dystrophy (DMD) is a serious degenerative muscular disease affecting males. Diagnosis usually occurs in childhood and is confirmed through genetic testing and/or muscle biopsy. Accompanying the disease are several nutrition-related concerns: growth, body composition, energy and protein requirements, constipation, swallowing difficulties, bone health, and complementary medicine. This review article addresses the nutrition aspects of DMD.

  1. [Congenital muscular dystrophies in children].

    PubMed

    Scavone-Mauro, Cristina; Barros, Graciela

    2013-09-06

    From the clinical and genetic point of view, congenital muscular dystrophies (CMD) are a heterogenic group of diseases within neuromuscular pathologies. The best known forms are: merosin deficiency CMD, collagen VI deficiency CMD, LMNA-related CMD, selenoprotein-related CMD (SEPN1) and alpha-dystroglycan-related CMD. They present with a broad spectrum of clinical phenotypes. Most of them are transmitted by recessive autosomal inheritance. The initial manifestations very often begin in infancy or in the neonatal period. There are clinical suspicions of the existence of hypotonia and paresis, and they are characterised by a dystrophic pattern in the muscular biopsy (muscle replaced by fibroadipose tissue, with necrosis and cell regeneration). Advances in the understanding of the molecular pathogenesis of CMD have made it possible to make further progress in the classification of the different subtypes. The aim of this review is to comment on the advances made in recent years as regards the classification of CMD in terms of genetics, the proteins involved and their clinical presentation.

  2. [Autosomal recessive limb-girdle muscular dystrophy].

    PubMed

    Hernández-Caballero, Marta E; Miranda-Duarte, Antonio; Escobar-Cedillo, Rosa E; Villegas-Castrejon, Hilda

    2010-10-16

    Muscular dystrophies are a heterogeneous group of hereditary diseases characterized by loss of muscle and weakness of non neurogenic origin. They are caused by mutations in one or more genes involved in the formation of muscle cells. The discovery of several proteins in the muscle began with the discovery of dystrophin, 130 years after the clinical description of muscular dystrophy. Currently, due to a better understanding of the biology of normal and diseased muscle, has achieved a classification at the molecular level of different types of muscular dystrophies, according to the protein that is affected. This has been particularly important for limb girdle muscular dystrophies, which present clinical features that can lead to confusion with Duchenne muscular dystrophy. Moreover, in recent years has encouraged the development of therapies in the near future could provide a solution for restoring the function of the muscle fiber.

  3. Dysregulation of calcium homeostasis in muscular dystrophies.

    PubMed

    Vallejo-Illarramendi, Ainara; Toral-Ojeda, Ivan; Aldanondo, Garazi; López de Munain, Adolfo

    2014-10-08

    Muscular dystrophies are a group of diseases characterised by the primary wasting of skeletal muscle, which compromises patient mobility and in the most severe cases originate a complete paralysis and premature death. Existing evidence implicates calcium dysregulation as an underlying crucial event in the pathophysiology of several muscular dystrophies, such as dystrophinopathies, calpainopathies or myotonic dystrophy among others. Duchenne muscular dystrophy is the most frequent myopathy in childhood, and calpainopathy or LGMD2A is the most common form of limb-girdle muscular dystrophy, whereas myotonic dystrophy is the most frequent inherited muscle disease worldwide. In this review, we summarise recent advances in our understanding of calcium ion cycling through the sarcolemma, the sarcoplasmic reticulum and mitochondria, and its involvement in the pathogenesis of these dystrophies. We also discuss some of the clinical implications of recent findings regarding Ca2+ handling as well as novel approaches to treat muscular dystrophies targeting Ca2+ regulatory proteins.

  4. Physiology of respiratory disturbances in muscular dystrophies

    PubMed Central

    Lo Mauro, Antonella

    2016-01-01

    Muscular dystrophy is a group of inherited myopathies characterised by progressive skeletal muscle wasting, including of the respiratory muscles. Respiratory failure, i.e. when the respiratory system fails in its gas exchange functions, is a common feature in muscular dystrophy, being the main cause of death, and it is a consequence of lung failure, pump failure or a combination of the two. The former is due to recurrent aspiration, the latter to progressive weakness of respiratory muscles and an increase in the load against which they must contract. In fact, both the resistive and elastic components of the work of breathing increase due to airway obstruction and chest wall and lung stiffening, respectively. The respiratory disturbances in muscular dystrophy are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and sleep disordered breathing. They can be present at different rates according to the type of muscular dystrophy and its progression, leading to different onset of each symptom, prognosis and degree of respiratory involvement. Key points A common feature of muscular dystrophy is respiratory failure, i.e. the inability of the respiratory system to provide proper oxygenation and carbon dioxide elimination. In the lung, respiratory failure is caused by recurrent aspiration, and leads to hypoxaemia and hypercarbia. Ventilatory failure in muscular dystrophy is caused by increased respiratory load and respiratory muscles weakness. Respiratory load increases in muscular dystrophy because scoliosis makes chest wall compliance decrease, atelectasis and fibrosis make lung compliance decrease, and airway obstruction makes airway resistance increase. The consequences of respiratory pump failure are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and

  5. Osteoprotegerin protects against muscular dystrophy.

    PubMed

    Dufresne, Sébastien S; Dumont, Nicolas A; Bouchard, Patrice; Lavergne, Éliane; Penninger, Josef M; Frenette, Jérôme

    2015-04-01

    Receptor-activator of NF-κB, its ligand RANKL, and the soluble decoy receptor osteoprotegerin are the key regulators of osteoclast differentiation and bone remodeling. Although there is a strong association between osteoporosis and skeletal muscle atrophy/dysfunction, the functional relevance of a particular biological pathway that synchronously regulates bone and skeletal muscle physiopathology still is elusive. Here, we show that muscle cells can produce and secrete osteoprotegerin and pharmacologic treatment of dystrophic mdx mice with recombinant osteoprotegerin muscles. (Recombinant osteoprotegerin-Fc mitigates the loss of muscle force in a dose-dependent manner and preserves muscle integrity, particularly in fast-twitch extensor digitorum longus.) Our data identify osteoprotegerin as a novel protector of muscle integrity, and it potentially represents a new therapeutic avenue for both muscular diseases and osteoporosis.

  6. Statistical insights into major human muscular diseases.

    PubMed

    Gupta, Shakti; Kim, Sung-Min; Wang, Yu; Dinasarapu, Ashok Reddy; Subramaniam, Shankar

    2014-07-15

    Muscular diseases lead to muscle fiber degeneration, impairment of mobility, and in some cases premature death. Many of these muscular diseases are largely idiopathic. The goal of this study was to identify biomarkers based on their functional role and possible mechanisms of pathogenesis, specific to individual muscular disease. We analyzed the muscle transcriptome from five major muscular diseases: acute quadriplegic myopathy (AQM), amyotrophic lateral sclerosis (ALS), mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), dermatomyositis (DM) and polymyositis (PM) using pairwise statistical comparison to identify uniquely regulated genes in each muscular disease. The genome-wide information encoded in the transcriptome provided biomarkers and functional insights into dysregulation in each muscular disease. The analysis showed that the dysregulation of genes in forward membrane pathway, responsible for transmitting action potential from neural excitation, is unique to AQM, while the dysregulation of myofibril genes, determinant of the mechanical properties of muscle, is unique to ALS, dysregulation of ER protein processing, responsible for correct protein folding, is unique to DM, and upregulation of immune response genes is unique to PM. We have identified biomarkers specific to each muscular disease which can be used for diagnostic purposes.

  7. Porcine models of muscular dystrophy.

    PubMed

    Selsby, Joshua T; Ross, Jason W; Nonneman, Dan; Hollinger, Katrin

    2015-01-01

    Duchenne muscular dystrophy is a progressive, fatal, X-linked disease caused by a failure to accumulate the cytoskeletal protein dystrophin. This disease has been studied using a variety of animal models including fish, mice, rats, and dogs. While these models have contributed substantially to our mechanistic understanding of the disease and disease progression, limitations inherent to each model have slowed the clinical advancement of therapies, which necessitates the development of novel large-animal models. Several porcine dystrophin-deficient models have been identified, although disease severity may be so severe as to limit their potential contributions to the field. We have recently identified and completed the initial characterization of a natural porcine model of dystrophin insufficiency. Muscles from these animals display characteristic focal necrosis concomitant with decreased abundance and localization of dystrophin-glycoprotein complex components. These pigs recapitulate many of the cardinal features of muscular dystrophy, have elevated serum creatine kinase activity, and preliminarily appear to display altered locomotion. They also suffer from sudden death preceded by EKG abnormalities. Pig dystrophinopathy models could allow refinement of dosing strategies in human-sized animals in preparation for clinical trials. From an animal handling perspective, these pigs can generally be treated normally, with the understanding that acute stress can lead to sudden death. In summary, the ability to create genetically modified pig models and the serendipitous discovery of genetic disease in the swine industry has resulted in the emergence of new animal tools to facilitate the critical objective of improving the quality and length of life for boys afflicted with such a devastating disease.

  8. Duchenne muscular dystrophy: current cell therapies

    PubMed Central

    Sienkiewicz, Dorota; Okurowska-Zawada, Bożena; Paszko-Patej, Grażyna; Kawnik, Katarzyna

    2015-01-01

    Duchenne muscular dystrophy is a genetically determined X-linked disease and the most common, progressive pediatric muscle disorder. For decades, research has been conducted to find an effective therapy. This review presents current therapeutic methods for Duchenne muscular dystrophy, based on scientific articles in English published mainly in the period 2000 to 2014. We used the PubMed database to identify and review the most important studies. An analysis of contemporary studies of stem cell therapy and the use of granulocyte colony-stimulating factor (G-CSF) in muscular dystrophy was performed. PMID:26136844

  9. Reality television and the muscular male ideal.

    PubMed

    Dallesasse, Starla L; Kluck, Annette S

    2013-06-01

    Although researchers have examined the negative effects of viewing reality television (RTV) on women's body image, this research has not been extended to men. Exploring the extent to which RTV depicts men who embody the muscular ideal may enhance our understanding of the potential influence of this media genre. We explored the extent to which RTV depicted men who embodied the muscular ideal using a quantitative content analysis. Based on binomial tests, the primary male cast members of programs airing on networks popular among young adult men during the Fall 2009 broadcast season were more muscular, with lower levels of body fat, than average U.S. men. The chest-to-waist and shoulder-to-waist ratios of these cast members did not differ as a function of program type (i.e., reality drama, endurance, and romance). Young men who view RTV programs included in the present study would be exposed to an unrepresentative muscular ideal.

  10. Genetics Home Reference: Fukuyama congenital muscular dystrophy

    MedlinePlus

    ... Fujii T, Aiba H, Toda T. Seizure-genotype relationship in Fukuyama-type congenital muscular dystrophy. Brain Dev. ... healthcare professional . About Genetics Home Reference Site Map Customer Support Selection Criteria for Links USA.gov Copyright ...

  11. Genetics Home Reference: oculopharyngeal muscular dystrophy

    MedlinePlus

    ... usually droopy eyelids ( ptosis ), followed by difficulty swallowing (dysphagia). The swallowing difficulties begin with food, but as ... Encyclopedia: Ptosis Health Topic: Muscular Dystrophy Health Topic: Swallowing Disorders Genetic and Rare Diseases Information Center (1 link) ...

  12. How Do People Cope with Muscular Dystrophy?

    MedlinePlus

    ... section. How do people cope with muscular dystrophy (MD)? Although MD presents many challenges in many different aspects of daily life, those with MD enjoy full lives. Advances in drug therapies, physical ...

  13. Targeting latent TGFβ release in muscular dystrophy.

    PubMed

    Ceco, Ermelinda; Bogdanovich, Sasha; Gardner, Brandon; Miller, Tamari; DeJesus, Adam; Earley, Judy U; Hadhazy, Michele; Smith, Lucas R; Barton, Elisabeth R; Molkentin, Jeffery D; McNally, Elizabeth M

    2014-10-22

    Latent transforming growth factor-β (TGFβ) binding proteins (LTBPs) bind to inactive TGFβ in the extracellular matrix. In mice, muscular dystrophy symptoms are intensified by a genetic polymorphism that changes the hinge region of LTBP, leading to increased proteolytic susceptibility and TGFβ release. We have found that the hinge region of human LTBP4 was also readily proteolysed and that proteolysis could be blocked by an antibody to the hinge region. Transgenic mice were generated to carry a bacterial artificial chromosome encoding the human LTBP4 gene. These transgenic mice displayed larger myofibers, increased damage after muscle injury, and enhanced TGFβ signaling. In the mdx mouse model of Duchenne muscular dystrophy, the human LTBP4 transgene exacerbated muscular dystrophy symptoms and resulted in weaker muscles with an increased inflammatory infiltrate and greater LTBP4 cleavage in vivo. Blocking LTBP4 cleavage may be a therapeutic strategy to reduce TGFβ release and activity and decrease inflammation and muscle damage in muscular dystrophy.

  14. [Ceruloplasmin in patients with Duchenne muscular dystrophy].

    PubMed

    Reyes, J; Holmgren, J; Colombo, M

    1991-03-01

    Duchenne muscular dystrophy is a well defined form of sex linked inherited muscular disease. Approximately 1/3 of cases are the product of a new mutation. We studied 20 patients with this disease and 19 heterozygous females. Ceruloplasmin levels were significantly higher in patients compared to controls. A possible protective role of this enzyme against oxydating agents may help prevent peroxydation of lipids from the smooth muscle cell membrane.

  15. Duchenne muscular dystrophy: the management of scoliosis

    PubMed Central

    Gardner, Adrian C.; Roper, Helen P.; Chikermane, Ashish A.; Tatman, Andrew J.

    2016-01-01

    This study summaries the current management of scoliosis in patients with Duchenne Muscular Dystrophy. A literature review of Medline was performed and the collected articles critically appraised. This literature is discussed to give an overview of the current management of scoliosis within Duchenne Muscular Dystrophy. Importantly, improvements in respiratory care, the use of steroids and improving surgical techniques have allowed patients to maintain quality of life and improved life expectancy in this patient group. PMID:27757431

  16. Muscular fatigue: considerations for dance.

    PubMed

    Wyon, Matthew A; Koutedakis, Yiannis

    2013-01-01

    Muscular fatigue can be defined as the failure to maintain an expected power output. It is a multifaceted phenomenon that incorporates metabolic, neural and neuromuscular components, among others. Metabolic causes of fatigue are associated with the ability to maintain energy supply during exercise, the speed at which homeostasis is achieved post-exercise, and the effects of high intensity exercise by-products on the peripheral neuromuscular system. Research has indicated that the central nervous system plays a protective role in preventing catastrophic muscle damage by reducing the intensity and frequency of propagation founded on biofeedback from the muscle cells. The duration and particularly the type of physical activity play a role in the development of muscle fatigue, with impact or weightbearing exercises, such as dance, producing increased symptoms compared to non-impact or non-weightbearing equivalents. The effects of prolonged exercise and the associated increased levels of muscle fatigue that may lead to compromises in neuromuscular propagation need to be considered in dance.

  17. Therapeutics in duchenne muscular dystrophy.

    PubMed

    Strober, Jonathan B

    2006-04-01

    Duchenne muscular dystrophy (DMD) is a fatal disorder affecting approximately 1 in 3,500 live born males, characterized by progressive muscle weakness. Several different strategies are being investigated in developing a cure for this disorder. Until a cure is found, therapeutic and supportive care is essential in preventing complications and improving the afflicted child's quality of life. Currently, corticosteroids are the only class of drug that has been extensively studied in this condition, with controversy existing over the use of these drugs, especially in light of the multiple side effects that may occur. The use of nutritional supplements has expanded in recent years as researchers improve our abilities to use gene and stem cell therapies, which will hopefully lead to a cure soon. This article discusses the importance of therapeutic interventions in children with DMD, the current debate over the use of corticosteroids to treat this disease, the growing use of natural supplements as a new means of treating these boys and provides an update on the current state of gene and stem cell therapies.

  18. Bone and Spinal Muscular Atrophy.

    PubMed

    Vai, Silvia; Bianchi, Maria Luisa; Moroni, Isabella; Mastella, Chiara; Broggi, Francesca; Morandi, Lucia; Arnoldi, Maria Teresa; Bussolino, Chiara; Baranello, Giovanni

    2015-10-01

    Spinal Muscular Atrophy (SMA) is an autosomal recessive neuromuscular disease, leading to progressive denervation atrophy in the involved skeletal muscles. Bone status has been poorly studied. We assessed bone metabolism, bone mineral density (BMD) and fractures in 30 children (age range 15-171 months) affected by SMA types 2 and 3. Eighteen children (60%) had higher than normal levels of CTx (bone resorption marker); 25-OH vitamin D was in the lower range of normal (below 20 ng/ml in 9 children and below 12 ng/ml in 2). Lumbar spine BMAD (bone mineral apparent density) Z-score was below -1.5 in 50% of children. According to clinical records, four children had sustained four peripheral fractures; on spine X-rays, we observed 9 previously undiagnosed vertebral fractures in 7 children. There was a significant inverse regression between PTH and 25-OH D levels, and a significant regression between BMC and BMAD values and the scores of motor-functional tests. Even if this study could not establish the pathogenesis of bone derangements in SMA, its main findings - reduced bone density, low 25OH vitamin D levels, increased bone resorption markers and asymptomatic vertebral fractures also in very young patients - strongly suggest that even young subjects affected by SMA should be considered at risk of osteopenia and even osteoporosis and fractures.

  19. [Upper limb functional assessment scale for children with Duchenne muscular dystrophy and Spinal muscular atrophy].

    PubMed

    Escobar, Raúl G; Lucero, Nayadet; Solares, Carmen; Espinoza, Victoria; Moscoso, Odalie; Olguín, Polín; Muñoz, Karin T; Rosas, Ricardo

    2017-02-01

    Duchenne muscular dystrophy (DMD) and Spinal muscular atrophy (SMA) causes significant disability and progressive functional impairment. Readily available instruments that assess functionality, especially in advanced stages of the disease, are required to monitor the progress of the disease and the impact of therapeutic interventions.

  20. Feline Muscular Dystrophy with Dystrophin Deficiency

    PubMed Central

    Carpenter, James L.; Hoffman, Eric P.; Romanul, Flaviu C. A.; Kunkel, Louis M.; Rosales, Remedios K.; Ma, Nancy S. F.; Dasbach, James J.; Rae, John F.; Moore, Frances M.; McAfee, Mary B.; Pearce, Laurie K.

    1989-01-01

    This is the first description of a dystrophin-Deficient muscular dystrophy in domestic cats. The disorder appears to be of X-linked inheritance because it affected both males of a litter of four kittens. Immunoblotting and immunofluorescent detection of dystrophin showed dystrophin present in control cat muscle but no detectable dystrophin in either affected cat. The feline muscular dystrophy was progressive and histopathologically resembled human Duchenne/Becker muscular dystrophy except for the lack of fat infiltration and the presence of prominent hypertrophy of both muscle fibers and muscles groups in the feline disorder. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7Figure 8Figure 9 PMID:2683799

  1. Job rotation: Effects on muscular activity variability.

    PubMed

    Rodriguez, Andres C; Barrero, Lope H

    2017-04-01

    Job rotation strategies have been used for years as an administrative intervention to reduce the risk of musculoskeletal disorders. The benefits of job rotation have been hypothesized to occur via changes in muscular activity variability (MAV). However, the effect of job rotation on MAV has not been fully analyzed in a literature review. A wide search was conducted to identify studies testing the effect of different job rotation strategies on MAV. Twenty-six studies of acceptable quality were included. Several studies on different types of tasks supported the view that job rotation can increase muscular activity variability, particularly with strategies such as alternating tasks and pace changes. However, it remains uncertain whether such variability changes immediately translate into benefits for the worker because little evidence was found that showed simultaneous changes in different muscular groups. Additionally, variability was occasionally achieved at the expense of average activity in the assessed muscles.

  2. Circulating Biomarkers for Duchenne Muscular Dystrophy

    PubMed Central

    Aartsma-Rus, Annemieke; Spitali, Pietro

    2015-01-01

    Abstract Duchenne muscular dystrophy is the most common form of muscular dystrophy. Genetic and biochemical research over the years has characterized the cause, pathophysiology and development of the disease providing several potential therapeutic targets and/or biomarkers. High throughput – omic technologies have provided a comprehensive understanding of the changes occurring in dystrophic muscles. Murine and canine animal models have been a valuable source to profile muscles and body fluids, thus providing candidate biomarkers that can be evaluated in patients. This review will illustrate known circulating biomarkers that could track disease progression and response to therapy in patients affected by Duchenne muscular dystrophy. We present an overview of the transcriptomic, proteomic, metabolomics and lipidomic biomarkers described in literature. We show how studies in muscle tissue have led to the identification of serum and urine biomarkers and we highlight the importance of evaluating biomarkers as possible surrogate endpoints to facilitate regulatory processes for new medicinal products. PMID:27858763

  3. Genetics Home Reference: limb-girdle muscular dystrophy

    MedlinePlus

    ... girdle muscular dystrophy is classified based on its inheritance pattern and genetic cause. Limb-girdle muscular dystrophy type ... includes forms of the disorder that have an inheritance pattern called autosomal dominant . Mutations in the LMNA gene ...

  4. Advances in gene therapy for muscular dystrophies

    PubMed Central

    Abdul-Razak, Hayder; Malerba, Alberto; Dickson, George

    2016-01-01

    Duchenne muscular dystrophy (DMD) is a recessive lethal inherited muscular dystrophy caused by mutations in the gene encoding dystrophin, a protein required for muscle fibre integrity. So far, many approaches have been tested from the traditional gene addition to newer advanced approaches based on manipulation of the cellular machinery either at the gene transcription, mRNA processing or translation levels. Unfortunately, despite all these efforts, no efficient treatments for DMD are currently available. In this review, we highlight the most advanced therapeutic strategies under investigation as potential DMD treatments. PMID:27594988

  5. Cellular and molecular mechanisms underlying muscular dystrophy

    PubMed Central

    2013-01-01

    The muscular dystrophies are a group of heterogeneous genetic diseases characterized by progressive degeneration and weakness of skeletal muscle. Since the discovery of the first muscular dystrophy gene encoding dystrophin, a large number of genes have been identified that are involved in various muscle-wasting and neuromuscular disorders. Human genetic studies complemented by animal model systems have substantially contributed to our understanding of the molecular pathomechanisms underlying muscle degeneration. Moreover, these studies have revealed distinct molecular and cellular mechanisms that link genetic mutations to diverse muscle wasting phenotypes. PMID:23671309

  6. 9 CFR 311.35 - Muscular inflammation, degeneration, or infiltration.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Muscular inflammation, degeneration, or infiltration. 311.35 Section 311.35 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... PARTS § 311.35 Muscular inflammation, degeneration, or infiltration. (a) If muscular lesions are...

  7. Cometas: Das Lendas aos Fatos

    NASA Astrophysics Data System (ADS)

    Voelzke, M. R.

    O descobrimento de cometas, devido ao seu aparecimento espetacular, tem registro nas mais antigas culturas humanas. A primeira referência situa-se no ano de 1095 antes de Cristo [a.C.; HO; HO, 1962]. A quantidade de registros de descobrimentos cometários, principalmente provenientes do território chinês em particular e do oriente em geral, aumentou gradualmente a partir do quarto século depois de Cristo (d.C.). É de origem chinesa a primeira referência ao cometa P/Halley no ano de 240 a.C. [VOELZKE, 1993]. Com o desenvolvimento da astronomia relativamente às técnicas observacionais os descobrimentos bem como as observações cometárias aumentaram sensivelmente a partir do século XVII, sendo que a partir do século XIX um novo incremento ocorreu devido ao emprego da fotografia e a resultante melhora de sensibilidade na observação.

  8. Red-Green Color Vision Impairment in Duchenne Muscular Dystrophy

    PubMed Central

    Costa, Marcelo Fernandes ; Oliveira, Andre Gustavo Fernandes ; Feitosa-Santana, Claudia ; Zatz, Mayana ; Ventura, Dora Fix 

    2007-01-01

    The present study evaluated the color vision of 44 patients with Duchenne muscular dystrophy (DMD) (mean age 14.8 years; SD 4.9) who were submitted to a battery of four different color tests: Cambridge Colour Test (CCT), Neitz Anomaloscope, Ishihara, and American Optical Hardy-Rand-Rittler (AO H-R-R). Patients were divided into two groups according to the region of deletion in the dystrophin gene: upstream of exon 30 (n=12) and downstream of exon 30 (n=32). The control group was composed of 70 age-matched healthy male subjects with no ophthalmological complaints. Of the patients with DMD, 47% (21/44) had a red-green color vision defect in the CCT, confirmed by the Neitz Anomaloscope with statistical agreement (P<.001). The Ishihara and the AO H-R-R had a lower capacity to detect color defects—5% and 7%, respectively, with no statistical similarity between the results of these two tests nor between CCT and Anomaloscope results (P>.05). Of the patients with deletion downstream of exon 30, 66% had a red-green color defect. No color defect was found in the patients with deletion upstream of exon 30. A negative correlation between the color thresholds and age was found for the controls and patients with DMD, suggesting a nonprogressive color defect. The percentage (66%) of patients with a red-green defect was significantly higher than the expected <10% for the normal male population (P<.001). In contrast, patients with DMD with deletion upstream of exon 30 had normal color vision. This color defect might be partially explained by a retina impairment related to dystrophin isoform Dp260. PMID:17503325

  9. Red-green color vision impairment in Duchenne muscular dystrophy.

    PubMed

    Costa, Marcelo Fernandes; Oliveira, Andre Gustavo Fernandes; Feitosa-Santana, Claudia; Zatz, Mayana; Ventura, Dora Fix

    2007-06-01

    The present study evaluated the color vision of 44 patients with Duchenne muscular dystrophy (DMD) (mean age 14.8 years; SD 4.9) who were submitted to a battery of four different color tests: Cambridge Colour Test (CCT), Neitz Anomaloscope, Ishihara, and American Optical Hardy-Rand-Rittler (AO H-R-R). Patients were divided into two groups according to the region of deletion in the dystrophin gene: upstream of exon 30 (n=12) and downstream of exon 30 (n=32). The control group was composed of 70 age-matched healthy male subjects with no ophthalmological complaints. Of the patients with DMD, 47% (21/44) had a red-green color vision defect in the CCT, confirmed by the Neitz Anomaloscope with statistical agreement (P<.001). The Ishihara and the AO H-R-R had a lower capacity to detect color defects--5% and 7%, respectively, with no statistical similarity between the results of these two tests nor between CCT and Anomaloscope results (P>.05). Of the patients with deletion downstream of exon 30, 66% had a red-green color defect. No color defect was found in the patients with deletion upstream of exon 30. A negative correlation between the color thresholds and age was found for the controls and patients with DMD, suggesting a nonprogressive color defect. The percentage (66%) of patients with a red-green defect was significantly higher than the expected <10% for the normal male population (P<.001). In contrast, patients with DMD with deletion upstream of exon 30 had normal color vision. This color defect might be partially explained by a retina impairment related to dystrophin isoform Dp260.

  10. Complete atrioventricular block in Duchenne muscular dystrophy.

    PubMed

    Fayssoil, A; Orlikowski, D; Nardi, O; Annane, D

    2008-11-01

    Duchenne muscular dystrophy (DMD) is an inherited myogenic disorder due to mutations in the dystrophin gene on chromosome Xp21.1. It is characterized by progressive muscle wasting and weakness of variable distribution and severity. Heart is involved leading to heart failure. Conduction abnormalities are unusual. We report a case of complete atrio-ventricular block in a DMD patient.

  11. Coaction Effects on a Muscular Endurance Task

    ERIC Educational Resources Information Center

    Martens, Rainer; Landers, Daniel M.

    1969-01-01

    A common procedure in administering muscular endurance tests is to have several individuals perform the same task at the same time. A very old psychological concept known as social facilitation suggests that an individual's performance may be affected by the presence of others. (CK)

  12. [Muscular metastases. A case report (author's transl)].

    PubMed

    Trèves, R; Barruche, D; Desproges-Gotteron, R

    Muscular metastases are exceptionally reported. The authors present a case of crural neuralgia in relation with a localisation in the psoas iliacus of a gastric carcinoma. A review of literature defines the rarity of this facts (156 cases) the etiology (carcinome more often) and the explication who is still obscur.

  13. Visuospatial Attention Disturbance in Duchenne Muscular Dystrophy

    ERIC Educational Resources Information Center

    De Moura, Maria Clara Drummond Soares; do Valle, Luiz Eduardo Ribeiro; Resende, Maria Bernadete Dutra; Pinto, Katia Osternack

    2010-01-01

    Aim: The cognitive deficits present in the Duchenne muscular dystrophy (DMD) are not yet well characterized. Attention, considered to be the brain mechanism responsible for the selection of sensory stimuli, could be disturbed in DMD, contributing, at least partially, to the observed global cognitive deficit. The aim of this study was to…

  14. Prevalence of congenital muscular dystrophy in Italy

    PubMed Central

    Graziano, Alessandra; Bianco, Flaviana; D'Amico, Adele; Moroni, Isabella; Messina, Sonia; Bruno, Claudio; Pegoraro, Elena; Mora, Marina; Astrea, Guja; Magri, Francesca; Comi, Giacomo P.; Berardinelli, Angela; Moggio, Maurizio; Morandi, Lucia; Pini, Antonella; Petillo, Roberta; Tasca, Giorgio; Monforte, Mauro; Minetti, Carlo; Mongini, Tiziana; Ricci, Enzo; Gorni, Ksenija; Battini, Roberta; Villanova, Marcello; Politano, Luisa; Gualandi, Francesca; Ferlini, Alessandra; Muntoni, Francesco; Santorelli, Filippo Maria; Bertini, Enrico; Pane, Marika

    2015-01-01

    Objective: We provide a nationwide population study of patients with congenital muscular dystrophy in Italy. Methods: Cases were ascertained from the databases in all the tertiary referral centers for pediatric neuromuscular disorders and from all the genetic diagnostic centers in which diagnostic tests for these forms are performed. Results: The study includes 336 patients with a point prevalence of 0.563 per 100,000. Mutations were identified in 220 of the 336 (65.5%). The cohort was subdivided into diagnostic categories based on the most recent classifications on congenital muscular dystrophies. The most common forms were those with α-dystroglycan glycosylation deficiency (40.18%) followed by those with laminin α2 deficiency (24.11%) and collagen VI deficiency (20.24%). The forms of congenital muscular dystrophy related to mutations in SEPN1 and LMNA were less frequent (6.25% and 5.95%, respectively). Conclusions: Our study provides for the first time comprehensive epidemiologic information and point prevalence figures for each of the major diagnostic categories on a large cohort of congenital muscular dystrophies. The study also reflects the diagnostic progress in this field with an accurate classification of the cases according to the most recent gene discoveries. PMID:25653289

  15. [Duchenne and Becker muscular dystrophy in Chile].

    PubMed

    Holmgren, J; Reyes, J; Colombo, M; Blanco, M A

    1992-03-01

    Duchenne muscular dystrophy is one of the best known forms of muscular dystrophy. The incidence in different countries varies from 130 to 390 per million male live births. Becker variety may be considered a mild form of Duchenne dystrophy, with an incidence 10 times lower. A sex linked recessive inheritance is involved in both forms, the affected gene is placed at locus X21. The incidence of both forms in Chile is similar to that reported worldwide, and has been increasing since 1950. Increased CK and LDH levels are confirmed in patients, and overall, they are also higher in female carriers. However only 26% of carriers have increased CK levels and 21% increased LDH levels, compared to normal subjects. Electromyograms show myopathic characteristics in all carrier women. The scope of a prospective clinical, genetic and epidemiologic study currently underway is discussed.

  16. Progress in therapy for Duchenne muscular dystrophy.

    PubMed

    Fairclough, Rebecca J; Bareja, Akshay; Davies, Kay E

    2011-11-01

    Duchenne muscular dystrophy is a devastating muscular dystrophy of childhood. Mutations in the dystrophin gene destroy the link between the internal muscle filaments and the extracellular matrix, resulting in severe muscle weakness and progressive muscle wasting. There is currently no cure and, whilst palliative treatment has improved, affected boys are normally confined to a wheelchair by 12 years of age and die from respiratory or cardiac complications in their twenties or thirties. Therapies currently being developed include mutation-specific treatments, DNA- and cell-based therapies, and drugs which aim to modulate cellular pathways or gene expression. This review aims to provide an overview of the different therapeutic approaches aimed at reconstructing the dystrophin-associated protein complex, including restoration of dystrophin expression and upregulation of the functional homologue, utrophin.

  17. Congenital muscular torticollis: experience of 14 cases.

    PubMed

    Das, B K; Matin, A; Hassan, G Z; Hossain, M Z; Zaman, M A

    2010-10-01

    Congenital Muscular Torticollis (CMT) is a postural deformity of head and neck detected at birth or shortly after birth, primarily resulting from unilateral shortening of Sternocleidomastoid Muscle (SCM). In neonates and infants, patient may cure conservatively by physiotherapy but surgery is the treatment of choice for children and adolescents. There are various techniques of surgery. Here we show our experience regarding management of congenital muscular torticollis. In the present retrospective case series, fourteen patients of congenital muscular torticollis were treated. The cases were enrolled between Nov' 2005 to Oct' 2007 in Bangabandhu Sheikh Mujib Medical University, Gonosasthaya Somaj Vittik Medical College Hospital, Dhaka and different private clinics of Dhaka city of Bangladesh. Neonates and infants were treated conservatively with physiotherapy and others treated surgically by transection of both sternal and clavicular head of SCM under general anesthesia. Operated patients were released on following post operative day with advised to do physiotherapy. Patients age range from 7 days to 15 years of which ten were female and four male. SCM was shortened in all cases (8 on right side and 6 on left side). Eleven were female and three male. Of 14 patients, 2 neonates, 7 infants and 5 were more than 1 year age. There was no associated anomaly. Out of 9 neonates and infants 8 cured conservatively with physiotherapy and another one significantly improved. Six were treated surgically including one failed physiotherapy. Post operative period was uneventful and there was no complication. Results were evaluated clinically and comments of peers. Most of the patient of congenital muscular torticollis can be treated conservatively during infancy. Division of both sternal and clavicular head of SCM is easy and safe surgical technique for the treatment of CMT of older children and adolescents.

  18. Very severe spinal muscular atrophy (Type 0).

    PubMed

    Al Dakhoul, Suleiman

    2017-01-01

    This case report describes a rare phenotype of very severe spinal muscular atrophy (SMA) in a newborn who presented with reduced fetal movements in utero and significant respiratory distress at birth. The patient was homozygously deleted for exon 7 and exon 8 of the survival motor neuron gene 1. Very severe SMA should be considered in the differential diagnosis of respiratory distress at birth, and more research should be dedicated to investigate the genetic determinants of its widely variable phenotypes.

  19. Very severe spinal muscular atrophy (Type 0)

    PubMed Central

    Al Dakhoul, Suleiman

    2017-01-01

    This case report describes a rare phenotype of very severe spinal muscular atrophy (SMA) in a newborn who presented with reduced fetal movements in utero and significant respiratory distress at birth. The patient was homozygously deleted for exon 7 and exon 8 of the survival motor neuron gene 1. Very severe SMA should be considered in the differential diagnosis of respiratory distress at birth, and more research should be dedicated to investigate the genetic determinants of its widely variable phenotypes. PMID:28182029

  20. Diaphragmatic function in advanced Duchenne muscular dystrophy.

    PubMed

    Beck, Jennifer; Weinberg, Jan; Hamnegård, Carl-Hugo; Spahija, Jadranka; Olofson, Jan; Grimby, Gunnar; Sinderby, Christer

    2006-03-01

    The aim of this study was to assess diaphragm electrical activation and diaphragm strength in patients with advanced Duchenne muscular dystrophy during resting conditions. Eight patients with advanced Duchenne muscular dystrophy (age of 25 +/- 2 years) were studied during tidal breathing, maximal inspiratory capacity, maximal sniff inhalations, and magnetic stimulation of the phrenic nerves. Six patients were prescribed home mechanical ventilation (five non-invasive and one tracheotomy). Transdiaphragmatic pressure and diaphragm electrical activation were measured using an esophageal catheter. During tidal breathing (tidal volume 198 +/- 83 ml, breathing frequency 25 +/- 7), inspiratory diaphragm electrical activation was clearly detectable in seven out of eight patients and was 12 +/- 7 times above the noise level, and represented 45 +/- 19% of the maximum diaphragm electrical activation. Mean inspiratory transdiaphragmatic pressure during tidal breathing was 1.5 +/- 1.2 cmH2O, and during maximal sniff was 7.6 +/- 3.6 cmH2O. Twitch transdiaphragmatic pressure deflections could not be detected. This study shows that despite near complete loss of diaphragm strength in advanced Duchenne muscular dystrophy, diaphragm electrical activation measured with an esophageal electrode array remains clearly detectable in all but one patient.

  1. Diagnostic approach to the congenital muscular dystrophies

    PubMed Central

    Bönnemann, Carsten G.; Wang, Ching H.; Quijano-Roy, Susana; Deconinck, Nicolas; Bertini, Enrico; Ferreiro, Ana; Muntoni, Francesco; Sewry, Caroline; Béroud, Christophe; Mathews, Katherine D.; Moore, Steven A.; Bellini, Jonathan; Rutkowski, Anne; North, Kathryn N.

    2017-01-01

    Congenital muscular dystrophies (CMDs) are early onset disorders of muscle with histological features suggesting a dystrophic process. The congenital muscular dystrophies as a group encompass great clinical and genetic heterogeneity so that achieving an accurate genetic diagnosis has become increasingly challenging, even in the age of next generation sequencing. In this document we review the diagnostic features, differential diagnostic considerations and available diagnostic tools for the various CMD subtypes and provide a systematic guide to the use of these resources for achieving an accurate molecular diagnosis. An International Committee on the Standard of Care for Congenital Muscular Dystrophies composed of experts on various aspects relevant to the CMDs performed a review of the available literature as well as of the unpublished expertise represented by the members of the committee and their contacts. This process was refined by two rounds of online surveys and followed by a three-day meeting at which the conclusions were presented and further refined. The combined consensus summarized in this document allows the physician to recognize the presence of a CMD in a child with weakness based on history, clinical examination, muscle biopsy results, and imaging. It will be helpful in suspecting a specific CMD subtype in order to prioritize testing to arrive at a final genetic diagnosis. PMID:24581957

  2. Aerosol Observing System (AOS) Handbook

    SciTech Connect

    Jefferson, A

    2011-01-17

    The Aerosol Observing System (AOS) is a suite of in situ surface measurements of aerosol optical and cloud-forming properties. The instruments measure aerosol properties that influence the earth’s radiative balance. The primary optical measurements are those of the aerosol scattering and absorption coefficients as a function of particle size and radiation wavelength and cloud condensation nuclei (CCN) measurements as a function of percent supersaturation. Additional measurements include those of the particle number concentration and scattering hygroscopic growth. Aerosol optical measurements are useful for calculating parameters used in radiative forcing calculations such as the aerosol single-scattering albedo, asymmetry parameter, mass scattering efficiency, and hygroscopic growth. CCN measurements are important in cloud microphysical models to predict droplet formation.

  3. Ways of increasing muscular activity by means of isometric muscular exertion

    NASA Technical Reports Server (NTRS)

    Kovalik, A. V.

    1980-01-01

    The effect of isometric muscular exertion on the human body was investigated by having subjects perform basic movements in a sitting position in the conventional manner with additional muscle tension at 50% maximum force and at maximum force. The pulse, arterial pressure, skin temperature, respiratory rate, minute respiratory volume and electrical activity of the muscles involved were all measured. Performance of the exercises with maximum muscular exertion for 20 sec and without movement resulted in the greatest shifts in these indices; in the conventional manner substantial changes did not occur; and with isometric muscular exertion with 50% maximum force with and without movement, optimal functional shifts resulted. The latter is recommended for use in industrial exercises for the prevention of hypodynamia. Ten exercises are suggested.

  4. Threatened masculinity and muscularity: an experimental examination of multiple aspects of muscularity in men.

    PubMed

    Hunt, Christopher John; Gonsalkorale, Karen; Murray, Stuart B

    2013-06-01

    Two studies examined the threatened masculinity theory of male body dissatisfaction, which posits that threats to masculinity result in increased muscle dissatisfaction. In Study 1, a masculinity threat was followed by tasks examining confidence in physical ability and perceptions of current and ideal body shapes. Results showed that men who experienced a masculinity threat reported lower confidence in their physical ability and perceived themselves as less muscular than men who experienced an affirmation of their masculinity. In Study 2, men were asked to report their intention to increase muscularity and their appearance anxiety following a threat to masculinity. Results showed that men reported lower appearance anxiety and drive for muscularity when their masculinity was threatened than when their masculinity was affirmed. This apparent contradiction can be explained by noting that men may be motivated to deny appearance concerns following a threat to masculinity, as such concerns are equated with femininity.

  5. Media's influence on the drive for muscularity in undergraduates.

    PubMed

    Cramblitt, Brooke; Pritchard, Mary

    2013-12-01

    Although research has found that body ideals presented by the media influence women's body dissatisfaction, less is known about media's influence on men's body satisfaction. An online survey examining media use, the drive for muscularity, and internalization of appearance and body shape ideals was given to a sample of 311 participants comprised of both men and women. Results indicated (a) the more time men and women reported watching television, the higher their reported drive for muscularity (b) total hours of viewing sports-related, image-focused, and entertainment television related to increased drive for muscularity in women (c) drive for muscularity in men related to watching image-focused television and reading men's health magazines, and (d) internalization of athletic attitudes towards appearance mediated the relationship between total television watched and drive for muscularity in both genders. Clinicians may wish to utilize these findings when treating men and women suffering from drive for muscularity and body dysmorphia.

  6. SRAO: the first southern robotic AO system

    NASA Astrophysics Data System (ADS)

    Law, Nicholas M.; Ziegler, Carl; Tokovinin, Andrei

    2016-08-01

    We present plans for SRAO, the first Southern Robotic AO system. SRAO will use AO-assisted speckle imaging and Robo-AO-heritage high efficiency observing to confirm and characterize thousands of planet candidates produced by major new transit surveys like TESS, and is the first AO system to be capable of building a comprehensive several-thousand-target multiplicity survey at sub-AU scales across the main sequence. We will also describe results from Robo-AO, the first robotic LGS-AO system. Robo-AO has observed tens of thousands of Northern targets, often using a similar speckle or Lucky-Imaging assisted mode. SRAO will be a moderate-order natural-guide-star adaptive optics system which uses an innovative photoncounting wavefront sensor and EMCCD speckle-imaging camera to guide on faint stars with the 4.1m SOAR telescope. The system will produce diffraction-limited imaging in the NIR on targets as faint as mν = 16. In AO-assisted speckle imaging mode the system will attain the 30-mas visible diffraction limit on targets at least as faint as mν = 17. The system will be the first Southern hemisphere robotic adaptive optics system, with overheads an order of magnitude smaller than comparable systems. Using Robo-AO's proven robotic AO software, SRAO will be capable of observing overheads on sub-minute scales, allowing the observation of at least 200 targets per night. SRAO will attain three times the angular resolution of the Palomar Robo-AO system in the visible.

  7. [Treatment progress of Duchenne Muscular Dystrophy (DMD)].

    PubMed

    Smogorzewska, Elzbieta Monika; Weinberg, Kenneth I

    2004-01-01

    Duchenne muscular dystrophy (DMD) is a common lethal disease for which no effective treatment is currently available. There exists a mouse model of the disease in which the usefulness of gene therapy was established. However, no progress towards human application was made due to the lack of a proper method for gene delivery. During the past several years, researchers acquired data which led them to believe that bone marrow stem cells are capable of generating not only blood cells, but also liver, heart, skin, muscle, and other tissue. Although the term "stem cell plasticity" became very popular, other studies have suggested that bone marrow might contain different types of stem cells that can produce non-hematopoietic cells. For example, mesenchymal stem cell (MSC) in bone marrow give rise to osteocytes, chondrocytes, adipocytes, and skeletal muscle. Recently, researchers have been able to show that transplanted bone marrow cells can contribute to muscle cells in a human patient who was diagnosed with two genetic diseases: severe combined immunodeficiency (SCID) and Duchenne muscular dystrophy. The odds of this happening is estimated at one in seven million. The results of studying this patient's medical history were reported by collaborating researchers at Children's Hospital, Los Angeles and Children's Hospital, Boston in an article titled "Long-term persistence of donor nuclei in a Duchenne muscular dystrophy (DMD) patient receiving bone marrow transplantation" published in the September 2002 issue of the Journal of Clinical Investigation. This patient was transplanted 15 years ago at Children's Hospital Los Angeles with paternal HLA-haploidentical T cell-depleted bone marrow. He engrafted and became a hematopoietic chimera having T and NK lymphocytes of donor origin. Studies performed on the muscle biopsy from the patient 13 years after transplantation demonstrated that the muscle showed evidence of donor derived nuclei. In addition, analysis of his bone marrow

  8. Exon skipping therapy for Duchenne muscular dystrophy.

    PubMed

    Kole, Ryszard; Krieg, Arthur M

    2015-06-29

    Duchenne muscular dystrophy (DMD) is caused mostly by internal deletions in the gene for dystrophin, a protein essential for maintaining muscle cell membrane integrity. These deletions abrogate the reading frame and the lack of dystrophin results in progressive muscle deterioration. DMD patients experience progressive loss of ambulation, followed by a need for assisted ventilation, and eventual death in mid-twenties. By the method of exon skipping in dystrophin pre-mRNA the reading frame is restored and the internally deleted but functional dystrophin is produced. Two oligonucleotide drugs that induce desired exon skipping are currently in advanced clinical trials.

  9. Spinal and Bulbar Muscular Atrophy Overview

    PubMed Central

    Fischbeck, Kenneth H.

    2016-01-01

    Spinal and bulbar muscular atrophy is an X-linked neuromuscular disease caused by an expanded repeat in the androgen receptor gene. The mutant protein is toxic to motor neurons and muscle. The toxicity is ligand-dependent and likely involves aberrant interaction of the mutant androgen receptor with other nuclear factors leading to transcriptional dysregulation. Various therapeutic strategies have been effective in transgenic animal models, and the challenge now is to translate these strategies into safe and effective treatment in patients. PMID:26547319

  10. MagAO: status and science

    NASA Astrophysics Data System (ADS)

    Morzinski, Katie M.; Close, Laird M.; Males, Jared R.; Hinz, Phil M.; Esposito, Simone; Riccardi, Armando; Briguglio, Runa; Follette, Katherine B.; Pinna, Enrico; Puglisi, Alfio; Vezilj, Jennifer; Xompero, Marco; Wu, Ya-Lin

    2016-07-01

    "MagAO" is the adaptive optics instrument at the Magellan Clay telescope at Las Campanas Observatory, Chile. MagAO has a 585-actuator adaptive secondary mirror and 1000-Hz pyramid wavefront sensor, operating on natural guide stars from R-magnitudes of -1 to 15. MagAO has been in on-sky operation for 166 nights since installation in 2012. MagAO's unique capabilities are simultaneous imaging in the visible and infrared with VisAO and Clio, excellent performance at an excellent site, and a lean operations model. Science results from MagAO include the first ground-based CCD image of an exoplanet, demonstration of the first accreting protoplanets, discovery of a new wide-orbit exoplanet, and the first empirical bolometric luminosity of an exoplanet. We describe the status, report the AO performance, and summarize the science results. New developments reported here include color corrections on red guide stars for the wavefront sensor; a new field stop stage to facilitate VisAO imaging of extended sources; and eyepiece observing at the visible-light diffraction limit of a 6.5-m telescope. We also discuss a recent hose failure that led to a glycol coolant leak, and the recovery of the adaptive secondary mirror (ASM) after this recent (Feb. 2016) incident.

  11. Dysphagia in Duchenne Muscular Dystrophy Assessed by Validated Questionnaire

    ERIC Educational Resources Information Center

    Archer, Sally K.; Garrod, Rachel; Hart, Nicholas; Miller, Simon

    2013-01-01

    Background: Duchenne muscular dystrophy (DMD) leads to progressive muscular weakness and death, most typically from respiratory complications. Dysphagia is common in DMD; however, the most appropriate swallowing assessments have not been universally agreed and the symptoms of dysphagia remain under-reported. Aims: To investigate symptoms of…

  12. Systemic vascular function is associated with muscular power in adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-associated loss of muscular strength and muscular power are critical determinants of loss of physical function and progression to disability in older adults. In this study, we examined the association of systemic vascular function and measures of muscle strength and power in older adults. Measu...

  13. Contingent muscular tension during a choice reaction task.

    PubMed

    Araki, Masanobu; Choshi, Koji

    2006-06-01

    This study examined the effects of contingent muscular tension on a choice reaction task, and especially, the effects various amounts of muscular tension have on the information processing of choice reaction time. The reactive movement task included a choice reaction task. Ten right-handed healthy men (ages 18 to 19 years) underwent trials with stimulus presentation probabilities of 50% and 20% on the muscular tension task and choice reaction tasks. The conditions for the muscular tension tasks were divided into seven different conditions: 0%, 10%, 20%, 30%, 40%, 50%, and 60% of maximum voluntary contraction. On these tasks, subjects performed isometric contraction of the biceps brachii. The choice reaction task was a rapid extension of the left or right knee as a choice reaction. Measures were choice reaction time, movement time, and total reaction time. Analysis indicated that shortening choice reaction time of the left and right feet was observed under 10% muscular tension of maximum strength. Muscular tension appreciably influenced information processing, including choice reaction time. Muscular tension did not affect movement time. Results are discussed with respect to previous research and the optimal muscular tension for best performance.

  14. [Cardiac involvement in Duchenne muscular dystrophy].

    PubMed

    Fayssoil, Abdallah; Orlikowski, David; Nardi, Olivier; Annane, Djillali

    2008-04-01

    Duchenne muscular dystrophy (DMD) is an X-linked hereditary dystrophinopathy due to the absence of dystrophin, a cytoskeleton protein; it is the most frequent of the dystrophinopathies. DMD affects one newborn boy in 3500. The disease locus is found on the short arm of the X chromosome (Xp21). Dystrophin plays an important role in the maintenance of the cellular architecture and permits signal transduction between the cytoskeleton and the extracellular matrix. Its absence is expressed by peripheral muscular damage, most often at the pelvic girdle, and sometimes associated with pseudohypertrophy of the calf. The disease is very often complicated by cardiac damage that develops towards the end of adolescence, together with restrictive lung disease that will usually end up requiring respiratory support. The prognosis is severe. Doppler examination of the myocardial tissue helps to screen for subclinical myocardial damage. Therapeutic management is multidisciplinary. Medical treatment of cardiac involvement relies on the drugs already proved effective in chronic heart failure. Ongoing research is currently studying gene therapy.

  15. The superhealing MRL background improves muscular dystrophy

    PubMed Central

    2012-01-01

    Background Mice from the MRL or “superhealing” strain have enhanced repair after acute injury to the skin, cornea, and heart. We now tested an admixture of the MRL genome and found that it altered the course of muscle pathology and cardiac function in a chronic disease model of skeletal and cardiac muscle. Mice lacking γ-sarcoglycan (Sgcg), a dystrophin-associated protein, develop muscular dystrophy and cardiomyopathy similar to their human counterparts with limb girdle muscular dystrophy. With disruption of the dystrophin complex, the muscle plasma membrane becomes leaky and muscles develop increased fibrosis. Methods MRL/MpJ mice were bred with Sgcg mice, and cardiac function was measured. Muscles were assessed for fibrosis and membrane leak using measurements of hydroxyproline and Evans blue dye. Quantitative trait locus mapping was conducted using single nucleotide polymorphisms distinct between the two parental strains. Results Introduction of the MRL genome reduced fibrosis but did not alter membrane leak in skeletal muscle of the Sgcg model. The MRL genome was also associated with improved cardiac function with reversal of depressed fractional shortening and the left ventricular ejection fraction. We conducted a genome-wide analysis of genetic modifiers and found that a region on chromosome 2 was associated with cardiac, diaphragm muscle and abdominal muscle fibrosis. Conclusions These data are consistent with a model where the MRL genome acts in a dominant manner to suppress fibrosis in this chronic disease setting of heart and muscle disease. PMID:23216833

  16. Congenital muscular torticollis: evaluation and classification.

    PubMed

    Tatli, Burak; Aydinli, Nur; Caliskan, Mine; Ozmen, Meral; Bilir, Feride; Acar, Gonul

    2006-01-01

    In this investigation of congenital muscular torticollis, 311 infants treated consecutively for congenital torticollis over an 8-year period (1995-2003) at the Pediatric Neurology Clinic of Istanbul Medical Faculty, Istanbul University, Turkey were reviewed retrospectively. The clinical presentation, associated abnormalities, treatment, and outcomes of the overall group and of subgroups divided according to an ultrasonography-based classification were evaluated. All patients were evaluated using a standard approach: cervical ultrasonography was performed, and the patients were divided into two subgroups. Each group was scanned for other anomalies, and outcomes were compared. The mean age at diagnosis was 2.3 months; patients included in this study were 138 males and 173 females. Two clinical subgroups, comprised of sternomastoid tumors 85% and postural torticollis 15%, were identified. Passive range of motion was the initial treatment recommended for all of the patients. Follow-up data were available for all 311 patients; 95% experienced total resolution and 5% experienced subtotal resolution. We conclude that the majority of children with congenital muscular torticollis experience total resolution of symptoms. The success rate of conservative treatment is primarily dependent on the patients' age at the initiation of exercises and ultrasonographic findings.

  17. Elevated Expression of Moesin in Muscular Dystrophies.

    PubMed

    Pines, Mark; Levi, Oshrat; Genin, Olga; Lavy, Adi; Angelini, Corrado; Allamand, Valérie; Halevy, Orna

    2017-03-01

    Fibrosis is the main complication of muscular dystrophies. We identified moesin, a member of the ezrin-radixin-moesin family, in dystrophic muscles of mice representing Duchenne and congenital muscular dystrophies (DMD and CMD, respectively) and dysferlinopathy, but not in the wild type. High levels of moesin were also observed in muscle biopsy specimens from DMD, Ullrich CMD, and merosin-deficient CMD patients, all of which present high levels of fibrosis. The myofibroblasts, responsible for extracellular matrix protein synthesis, and the macrophages infiltrating the dystrophic muscles were the source of moesin. Moesin-positive cells were embedded within the fibrotic areas between the myofibers adjacent to the collagen type I fibers. Radixin was also synthesized by the myofibroblasts, whereas ezrin colocalized with the myofiber membranes. In animal models and patients' muscles, part of the moesin was in its active phosphorylated form. Inhibition of fibrosis by halofuginone, an antifibrotic agent, resulted in a major decrease in moesin levels in the muscles of DMD and CMD mice. In summary, the results of this study may pave the way for exploiting moesin as a novel target for intervention in MDs, and as part of a battery of biomarkers to evaluate treatment success in preclinical studies and clinical trials.

  18. Upper Girdle Imaging in Facioscapulohumeral Muscular Dystrophy

    PubMed Central

    Tasca, Giorgio; Monforte, Mauro; Iannaccone, Elisabetta; Laschena, Francesco; Ottaviani, Pierfrancesco; Leoncini, Emanuele; Boccia, Stefania; Galluzzi, Giuliana; Pelliccioni, Marco; Masciullo, Marcella; Frusciante, Roberto; Mercuri, Eugenio; Ricci, Enzo

    2014-01-01

    Background In Facioscapulohumeral muscular dystrophy (FSHD), the upper girdle is early involved and often difficult to assess only relying on physical examination. Our aim was to evaluate the pattern and degree of involvement of upper girdle muscles in FSHD compared with other muscle diseases with scapular girdle impairment. Methods We propose an MRI protocol evaluating neck and upper girdle muscles. One hundred-eight consecutive symptomatic FSHD patients and 45 patients affected by muscular dystrophies and myopathies with prominent upper girdle involvement underwent this protocol. Acquired scans were retrospectively analyzed. Results The trapezius (100% of the patients) and serratus anterior (85% of the patients) were the most and earliest affected muscles in FSHD, followed by the latissimus dorsi and pectoralis major, whilst spinati and subscapularis (involved in less than 4% of the patients) were consistently spared even in late disease stages. Asymmetry and hyperintensities on short-tau inversion recovery (STIR) sequences were common features, and STIR hyperintensities could also be found in muscles not showing signs of fatty replacement. The overall involvement appears to be disease-specific in FSHD as it significantly differed from that encountered in the other myopathies. Conclusions The detailed knowledge of single muscle involvement provides useful information for correctly evaluating patients' motor function and to set a baseline for natural history studies. Upper girdle imaging can also be used as an additional tool helpful in supporting the diagnosis of FSHD in unclear situations, and may contribute with hints on the currently largely unknown molecular pathogenesis of this disease. PMID:24932477

  19. Sleep disordered breathing in facioscapulohumeral muscular dystrophy.

    PubMed

    Della Marca, Giacomo; Frusciante, Roberto; Dittoni, Serena; Vollono, Catello; Buccarella, Cristina; Iannaccone, Elisabetta; Rossi, Monica; Scarano, Emanuele; Pirronti, Tommaso; Cianfoni, Alessandro; Mazza, Salvatore; Tonali, Pietro A; Ricci, Enzo

    2009-10-15

    Facioscapulohumeral muscular dystrophy (FSHD) is one of the most frequent forms of muscular dystrophy. The aims of this study were: 1) to evaluate the prevalence of sleep disordered breathing (SDB) in patients with FSHD; 2) to define the sleep-related respiratory patterns in FSHD patients with SDB; and 3) to find the clinical predictors of SDB. Fifty-one consecutive FSHD patients were enrolled, 23 women, mean age 45.7+/-12.3 years (range: 26-72). The diagnosis of FSHD was confirmed by genetic tests. All patients underwent medical and neurological evaluations, subjective evaluation of sleep and full-night laboratory-based polysomnography. Twenty patients presented SDB: 13 presented obstructive apneas, four presented REM related oxygen desaturations and three showed a mixed pattern. Three patients needed positive airways pressure. SDB was not related to the severity of the disease. Body mass index, neck circumference and daytime sleepiness did not allow prediction of SDB. In conclusion, the results suggest a high prevalence of SDB in patients with FSHD. The presence of SDB does not depend on the clinical severity of the disease. SDB is often asymptomatic, and no clinical or physical measure can reliably predict its occurrence. A screening of SDB should be included in the clinical assessment of FSHD.

  20. Social dominance orientation predicts drive for muscularity among British men.

    PubMed

    Swami, Viren; Neofytou, Rudolfos-Valentino; Jablonska, Joanna; Thirlwell, Holly; Taylor, Donna; McCreary, Donald R

    2013-09-01

    The present study tested the hypothesis that men's drive for muscularity would be associated with their valuation of domination, power, status, and aggression over others. A community sample of 359 men from London, UK, completed measures of drive for muscularity, social dominance orientation, right-wing authoritarianism, trait aggression, and need for power, as well as their demographic details. Bivariate correlations showed that greater drive for muscularity was significantly correlated with most of the measures and their subscales. However, in a multiple regression analysis, the only significant predictor of drive for muscularity was support for group-based dominance hierarchies (Adj. R(2)=.17). These results suggest that men's drive for muscularity is associated with a socio-political ideology that favours social dominance.

  1. Consensus statement on standard of care for congenital muscular dystrophies.

    PubMed

    Wang, Ching H; Bonnemann, Carsten G; Rutkowski, Anne; Sejersen, Thomas; Bellini, Jonathan; Battista, Vanessa; Florence, Julaine M; Schara, Ulrike; Schuler, Pamela M; Wahbi, Karim; Aloysius, Annie; Bash, Robert O; Béroud, Christophe; Bertini, Enrico; Bushby, Kate; Cohn, Ronald D; Connolly, Anne M; Deconinck, Nicolas; Desguerre, Isabelle; Eagle, Michelle; Estournet-Mathiaud, Brigitte; Ferreiro, Ana; Fujak, Albert; Goemans, Nathalie; Iannaccone, Susan T; Jouinot, Patricia; Main, Marion; Melacini, Paola; Mueller-Felber, Wolfgang; Muntoni, Francesco; Nelson, Leslie L; Rahbek, Jes; Quijano-Roy, Susana; Sewry, Caroline; Storhaug, Kari; Simonds, Anita; Tseng, Brian; Vajsar, Jiri; Vianello, Andrea; Zeller, Reinhard

    2010-12-01

    Congenital muscular dystrophies are a group of rare neuromuscular disorders with a wide spectrum of clinical phenotypes. Recent advances in understanding the molecular pathogenesis of congenital muscular dystrophy have enabled better diagnosis. However, medical care for patients with congenital muscular dystrophy remains very diverse. Advances in many areas of medical technology have not been adopted in clinical practice. The International Standard of Care Committee for Congenital Muscular Dystrophy was established to identify current care issues, review literature for evidence-based practice, and achieve consensus on care recommendations in 7 areas: diagnosis, neurology, pulmonology, orthopedics/rehabilitation, gastroenterology/ nutrition/speech/oral care, cardiology, and palliative care. To achieve consensus on the care recommendations, 2 separate online surveys were conducted to poll opinions from experts in the field and from congenital muscular dystrophy families. The final consensus was achieved in a 3-day workshop conducted in Brussels, Belgium, in November 2009. This consensus statement describes the care recommendations from this committee.

  2. Consensus Statement on Standard of Care for Congenital Muscular Dystrophies

    PubMed Central

    Wang, Ching H.; Bonnemann, Carsten G.; Rutkowski, Anne; Sejersen, Thomas; Bellini, Jonathan; Battista, Vanessa; Florence, Julaine M.; Schara, Ulrike; Schuler, Pamela M.; Wahbi, Karim; Aloysius, Annie; Bash, Robert O.; Béroud, Christophe; Bertini, Enrico; Bushby, Kate; Cohn, Ronald D.; Connolly, Anne M.; Deconinck, Nicolas; Desguerre, Isabelle; Eagle, Michelle; Estournet-Mathiaud, Brigitte; Ferreiro, Ana; Fujak, Albert; Goemans, Nathalie; Iannaccone, Susan T.; Jouinot, Patricia; Main, Marion; Melacini, Paola; Mueller-Felber, Wolfgang; Muntoni, Francesco; Nelson, Leslie L.; Rahbek, Jes; Quijano-Roy, Susana; Sewry, Caroline; Storhaug, Kari; Simonds, Anita; Tseng, Brian; Vajsar, Jiri; Vianello, Andrea; Zeller, Reinhard

    2016-01-01

    Congenital muscular dystrophies are a group of rare neuromuscular disorders with a wide spectrum of clinical phenotypes. Recent advances in understanding the molecular pathogenesis of congenital muscular dystrophy have enabled better diagnosis. However, medical care for patients with congenital muscular dystrophy remains very diverse. Advances in many areas of medical technology have not been adopted in clinical practice. The International Standard of Care Committee for Congenital Muscular Dystrophy was established to identify current care issues, review literature for evidence-based practice, and achieve consensus on care recommendations in 7 areas: diagnosis, neurology, pulmonology, orthopedics/rehabilitation, gastroenterology/ nutrition/speech/oral care, cardiology, and palliative care. To achieve consensus on the care recommendations, 2 separate online surveys were conducted to poll opinions from experts in the field and from congenital muscular dystrophy families. The final consensus was achieved in a 3-day workshop conducted in Brussels, Belgium, in November 2009. This consensus statement describes the care recommendations from this committee. PMID:21078917

  3. Congenital muscular torticollis and positional plagiocephaly.

    PubMed

    Kuo, Alice A; Tritasavit, Sophie; Graham, John M

    2014-02-01

    On the basis of observational studies, child health practitioners in primary care settings should consider the diagnosis of congenital muscular torticollis (CMT)in infants with risk factors from birth history for intrauterine malpositioning or constraint (C). On the basis of observational studies, CMT is often associated with other conditions, including positional plagiocephaly and gross motor delays from weakened truncal muscles and/or lack of head control in early infancy (C). On the basis of observational studies, child health practitioners should counsel parents that infants should be on their stomachs frequently whenever they are awake and under direct adult supervision to develop their prone motor skills (C). On the basis of consensus, early identification of CMT(with or without positional plagiocephaly) and prompt referral to a physical therapist experienced in the treatment of CMT should be considered to avoid more costly or invasive treatments, such as cranial orthoses or surgery (D).

  4. [Statin intolerance and associated muscular dysfunctions].

    PubMed

    Boulanger-Piette, Antoine; Bergeron, Jean; Desgreniers, Joël; Côté-Levesque, Michèle; Brassard, Dominic; Joanisse, Denis R; Frenette, Jérôme

    2015-12-01

    Hypercholesterolemia is a major risk factor for cardiovascular diseases. The 2012-2013 survey of Canada's public health measures revealed that dyslipidemia was present in 38% of the respondents aged between 18 and 79 years. According to the American College of Cardiology, the American Heart Association, the Canadian Cardiovascular Society and the Canadian Working Group Consensus, statins remain the treatment of choice for dyslipidemia and the reduction of cardiovascular risk. However, concerns and questions persist regarding statins use and safety, potential and harmful muscular side-effects, interactions with exercise, and molecular mechanisms of myotoxicity. The goal of the present review is to provide a clear picture of the clinical situation and to investigate possible mechanisms of statin-induced myopathy. A better understanding of muscle pathology in statin users is absolutely essential to minimize their muscle symptoms and to provide a sound clinical basis for the management of cardiovascular risk.

  5. [Vitamin D: skeletal and muscular effects].

    PubMed

    Thomas, Thierry; Briot, Karine

    2013-10-01

    Insufficient serum levels of 25-hydroxyvitamin D [25(OH)D] is a risk factor for osteoporosis. A new paradigm is emerging with the locally synthesized 1,25(OH)2D within osteoblasts and osteoclasts as the essential pathway for the effects of 25(OH)D in regulating bone remodeling via direct or indirect activation of the specific receptor VDR. Vitamin D has positive effects on fracture risk, muscular function and risk of falls; these effects are observed when serum levels of 25(OH)D are above 30 ng/ml (75 nmol/l). Vitamin D dosing interval may be relevant for reducing the risk of fracture, with evidence suggesting positive effects with short intervals of 3 months or less. It is recommended to maintain an optimal serum level of 25(OH)D when managing patients with osteoporosis or at risk of this bone disease.

  6. Neonatal muscular manifestations in mitochondrial disorders.

    PubMed

    Tulinius, Már; Oldfors, Anders

    2011-08-01

    During the last decade rapid development has occurred in defining nuclear gene mutations causing mitochondrial disease. Some of these newly defined gene mutations cause neonatal or early infantile onset of disease, often associated with severe progressive encephalomyopathy combined with other multi-organ involvement such as cardiomyopathy or hepatopathy and with early death. Findings suggesting myopathy in neonates are hypotonia, muscle weakness and wasting, and arthrogryposis. We aim to describe the clinical findings of patients with mitochondrial disease presenting with muscular manifestations in the neonatal period or in early infancy and in whom the genetic defect has been characterized. The majority of patients with neonatal onset of mitochondrial disease have mutations in nuclear genes causing dysfunction of the mitochondrial respiratory chain, leading to defective oxidative phosphorylation.

  7. Effects of muscular strength on cardiovascular risk factors and prognosis.

    PubMed

    Artero, Enrique G; Lee, Duck-chul; Lavie, Carl J; España-Romero, Vanesa; Sui, Xuemei; Church, Timothy S; Blair, Steven N

    2012-01-01

    Physical fitness is one of the strongest predictors of individual future health status. Together with cardiorespiratory fitness (CRF), muscular strength has been increasingly recognized in the pathogenesis and prevention of chronic disease. We review the most recent literature on the effect of muscular strength in the development of cardiovascular disease, with special interest in elucidating its specific benefits beyond those from CRF and body composition. Muscular strength has shown an independent protective effect on all-cause and cancer mortality in healthy middle-aged men, as well as in men with hypertension and patients with heart failure. It has also been inversely associated with age-related weight and adiposity gains, risk of hypertension, and prevalence and incidence of the metabolic syndrome. In children and adolescents, higher levels of muscular fitness have been inversely associated with insulin resistance, clustered cardiometabolic risk, and inflammatory proteins. Generally, the influence of muscular fitness was weakened but remained protective after considering CRF. Also, interestingly, higher levels of muscular fitness seems to some extent counteract the adverse cardiovascular profile of overweight and obese individuals. As many of the investigations have been conducted with non-Hispanic white men, it is important to examine how race/ethnicity and gender may affect these relationships. To conclude, most important effects of resistance training are also summarized, to better understand how higher levels of muscular fitness may result in a better cardiovascular prognosis and survival.

  8. Contribution of trunk muscularity on sprint run.

    PubMed

    Kubo, T; Hoshikawa, Y; Muramatsu, M; Iida, T; Komori, S; Shibukawa, K; Kanehisa, H

    2011-03-01

    This study aimed to investigate how the trunk muscularity is related to sprint running performance. In 23 youth soccer players, the cross-sectional images at the mid level of each of L1-L2, L2-L3, L3-L4, L4-L5, and L5-S1 were obtained using magnetic resonance imaging to determine the cross-sectional areas (CSAs) of rectus abdominis, oblique, psoas major, quadratus lumborum and erector spinae muscles. The times taken to sprint over 20 m were measured, and the mean velocity of running was calculated for each of the 2 distances (V (10 m) and V (20 m)) and for the distance from 10 m to 20 m (V (10-20 m)). The CSA values of the 5 slice levels for all muscles except for the quadratus lumborum and those of the 3 slice levels (L1-L2, L2-L3 and L3-L4) for the quadratus lumborum were averaged and expressed relative to the two-third power of body mass (CSA/BM (2/3)). The CSA/BM (2/3) values of the erector spinae and quadratus lumborum were selected as significant contributors to predict V (10 m) ( R(2)=0.450), V (20 m) ( R(2)=0.504) and V (10-20 m) ( R(2)=0.420). The current results indicate that the muscularity of the erector spinae and quadratus lumborum contributes to achieving a high performance in sprint running over distances of less than 20 m.

  9. Respiratory muscle dysfunction in facioscapulohumeral muscular dystrophy.

    PubMed

    Santos, Dante Brasil; Boussaid, Ghilas; Stojkovic, Tanya; Orlikowski, David; Letilly, Nadege; Behin, Anthony; Butel, Sandrine; Lofaso, Frédéric; Prigent, Hélène

    2015-08-01

    Respiratory insufficiency in facioscapulohumeral muscular dystrophy has rarely been studied. We compared two age- and sex-matched groups of 29 patients, with and without respiratory dysfunction. Tests in the 29 patients with respiratory dysfunction suggested predominant expiratory muscle dysfunction, leading to ineffective cough in 17 patients. Supine and upright vital capacities were not different (P = 0.76), suggesting absence of diaphragmatic dysfunction. By stepwise regression, only expiratory reserve volume correlated with the Walton and Gardner-Medwin score (R(2) = 0.503; P = 0.001). Compared to controls, patients with respiratory dysfunction had higher values for the Walton and Gardner-Medwin score (6.1 ± 1.9 vs. 3.2 ± 1.2; P <0.0001) and body mass index (26.9 ± 6.0 vs. 22.9 ± 4.0 kg/m(2); P = 0.003) and a smaller number of D4Z4 allele repeats (4.8 ± 1.6 vs. 5.7 ± 1.8; P = 0.05). Mechanical ventilation was required eventually in 20 patients, including 14 who were wheelchair bound. Three patients had acute respiratory failure requiring mechanical ventilation; 16 patients had poor airway clearance, including 10 with sleep apnea syndrome, responsible in 7 for chronic hypercapnia. Two patients presented isolated severe sleep apnea syndrome. Respiratory dysfunction in facioscapulohumeral muscular dystrophy is predominantly related to expiratory muscle weakness. Respiratory function and cough effectiveness should especially be monitored in patients with severe motor impairment and high body mass index.

  10. Determination of muscular fatigue in elite runners.

    PubMed

    Hanon, Christine; Thépaut-Mathieu, Chantalle; Vandewalle, Henry

    2005-05-01

    This study analyses the changes in the electromyographic activity (EMG) of six major muscles of the leg during an incremental running test carried out on a treadmill. These muscles, the gluteus maximus (GM), biceps femoris (BF), vastus lateralis (VL), rectus femoris (RF), tibialis anterior (TA) and gastrocnemius (Ga) are known to have quite different functions during running. The aim of this study was to develop a methodology adapted to the analysis of integrated EMG (iEMG) running results, and to test the chronology of the onset of fatigue of the major muscles involved in running. Nine well-trained subjects [VO(2max) 76 (2.9) ml.min(-1).kg(-1)] took part in this study. They completed a running protocol consisting of 4 min stages, incrementally increasing in speed until exhaustion. The EMG signal was recorded during ten bursts of activation analysed separately at 45 s and 3 min 40 s of each stage. During running, consideration of the alteration in stride frequency with either an increase in speed or the onset of fatigue appears to be an indispensable part of the assessment of muscular fatigue. This allows the comparison of muscular activation between the various stage speeds by the use of common working units. Distance seems to be the only working unit that allows this comparison and thus the determination of the appearance of fatigue during running. The biarticular hip-mobilising muscles (RF and BF), which present two different bursts of activation during one running cycle, are the muscles that show the earliest signs of fatigue.

  11. Genetics and emerging treatments for Duchenne and Becker muscular dystrophy.

    PubMed

    Wein, Nicolas; Alfano, Lindsay; Flanigan, Kevin M

    2015-06-01

    Mutations in the DMD gene result in Duchenne or Becker muscular dystrophy due to absent or altered expression of the dystrophin protein. The more severe Duchenne muscular dystrophy typically presents around ages 2 to 5 with gait disturbance, and historically has led to the loss of ambulation by age 12. It is important for the practicing pediatrician, however, to be aware of other presenting signs, such as delayed motor or cognitive milestones, or elevated serum transaminases. Becker muscular dystrophy is milder, often presenting after age 5, with ambulation frequently preserved past 20 years and sometimes into late decades.

  12. How Physicians Support Mothers of Children with Duchenne Muscular Dystrophy.

    PubMed

    Fujino, Haruo; Saito, Toshio; Matsumura, Tsuyoshi; Shibata, Saki; Iwata, Yuko; Fujimura, Harutoshi; Shinno, Susumu; Imura, Osamu

    2015-09-01

    Communicating about Duchenne muscular dystrophy and its prognosis can be difficult for affected children and their family. We focused on how physicians provide support to the mothers of children with Duchenne muscular dystrophy who have difficulty communicating about the condition with their child. The eligible participants were certified child neurologists of the Japanese Society of Child Neurology. Participants responded to questionnaires consisting of free descriptions of a vignette of a child with Duchenne muscular dystrophy and a mother. We analyzed 263 responses of the participants. We found 4 themes on advising mothers, involving encouraging communication, family autonomy, supporting family, and considering the child's concerns. These results provide a better understanding of the communication between physicians and family members who need help sharing information with a child with Duchenne muscular dystrophy. These findings will assist clinical practitioners in supporting families and the affected children throughout the course of their illness.

  13. Efficacy of bipolar release in neglected congenital muscular torticollis patients.

    PubMed

    Seyhan, Nevra; Jasharllari, Lorenc; Keskin, Mustafa; Savacı, Nedim

    2012-06-01

    Surgical correction of the congenital muscular torticollis (CMT) is recommended for patients with unsuccessful conservative treatment. The aim of this study is to evaluate the efficacy of surgical release of congenital muscular torticollis in neglected cases. We retrospectively evaluated the data of our patients in terms of age, sex, clinical presentation, localization of the lesion, diagnostic tests, and additional abnormalities. The age at operation ranged from 6 to 23 years. Complete muscular release as determined by pre-operative and postoperative range of motion measurements was achieved in all of the patients by bipolar release. In this study, neck motion and head tilt showed marked improvement with surgical treatment in cases with CMT who were admitted to the hospital lately. Congenital muscular torticollis patients can benefit from surgical intervention above the age of 5. Bipolar release is an adequate and complication-free method.

  14. Perspectives of stem cell therapy in Duchenne muscular dystrophy.

    PubMed

    Meregalli, Mirella; Farini, Andrea; Belicchi, Marzia; Parolini, Daniele; Cassinelli, Letizia; Razini, Paola; Sitzia, Clementina; Torrente, Yvan

    2013-09-01

    Muscular dystrophies are heritable and heterogeneous neuromuscular disorders characterized by the primary wasting of skeletal muscle, usually caused by mutations in the proteins forming the link between the cytoskeleton and the basal lamina. As a result of mutations in the dystrophin gene, Duchenne muscular dystrophy patients suffer from progressive muscle atrophy and an exhaustion of muscular regenerative capacity. No efficient therapies are available. The evidence that adult stem cells were capable of participating in the regeneration of more than their resident organ led to the development of potential stem cell treatments for degenerative disorder. In the present review, we describe the different types of myogenic stem cells and their possible use for the progression of cell therapy in Duchenne muscular dystrophy.

  15. Low-intensity exercise, vascular occlusion, and muscular adaptations.

    PubMed

    Teramoto, Masaru; Golding, Lawrence A

    2006-01-01

    The study investigated the effects of low-intensity exercise on muscular fitness when combined with vascular occlusion. Nineteen college male and female students performed two sets of a 5-min step exercise using a 12-inch bench three times per week for 5 weeks. During the step exercise, blood flow to one leg was restricted (vascular occlusion) with a blood pressure cuff, while the other leg was not occluded. Muscular strength of the occluded leg was significantly increased over the nonoccluded leg (p < 0. 05). Muscular endurance and muscle mass were improved after 5 weeks of training (p < 0.05); however, the changes between the two legs were not significantly different (p > 0.05). Exercise with vascular occlusion has the potential to be an alternative form of training to promote muscular strength.

  16. Prospect of gene therapy for cardiomyopathy in hereditary muscular dystrophy

    PubMed Central

    Yue, Yongping; Binalsheikh, Ibrahim M.; Leach, Stacey B.; Domeier, Timothy L.; Duan, Dongsheng

    2016-01-01

    Introduction Cardiac involvement is a common feature in muscular dystrophies. It presents as heart failure and/or arrhythmia. Traditionally, dystrophic cardiomyopathy is treated with symptom-relieving medications. Identification of disease-causing genes and investigation on pathogenic mechanisms have opened new opportunities to treat dystrophic cardiomyopathy with gene therapy. Replacing/repairing the mutated gene and/or targeting the pathogenic process/mechanisms using alternative genes may attenuate heart disease in muscular dystrophies. Areas covered Duchenne muscular dystrophy is the most common muscular dystrophy. Duchenne cardiomyopathy has been the primary focus of ongoing dystrophic cardiomyopathy gene therapy studies. Here, we use Duchenne cardiomyopathy gene therapy to showcase recent developments and to outline the path forward. We also discuss gene therapy status for cardiomyopathy associated with limb-girdle and congenital muscular dystrophies, and myotonic dystrophy. Expert opinion Gene therapy for dystrophic cardiomyopathy has taken a slow but steady path forward. Preclinical studies over the last decades have addressed many fundamental questions. Adeno-associated virus-mediated gene therapy has significantly improved the outcomes in rodent models of Duchenne and limb girdle muscular dystrophies. Validation of these encouraging results in large animal models will pave the way to future human trials. PMID:27340611

  17. Outside in: The matrix as a modifier of muscular dystrophy.

    PubMed

    Quattrocelli, Mattia; Spencer, Melissa J; McNally, Elizabeth M

    2017-03-01

    Muscular dystrophies are genetic conditions leading to muscle degeneration and often, impaired regeneration. Duchenne Muscular Dystrophy is a prototypical form of muscular dystrophy, and like other forms of genetically inherited muscle diseases, pathological progression is variable. Variability in muscular dystrophy can arise from differences in the manner in which the primary mutation impacts the affected protein's function; however, clinical heterogeneity also derives from secondary mutations in other genes that can enhance or reduce pathogenic features of disease. These genes, called genetic modifiers, regulate the pathophysiological context of dystrophic degeneration and regeneration. Understanding the mechanistic links between genetic modifiers and dystrophic progression sheds light on pathologic remodeling, and provides novel avenues to therapeutically intervene to reduce muscle degeneration. Based on targeted genetic approaches and unbiased genomewide screens, several modifiers have been identified for muscular dystrophy, including extracellular agonists of signaling cascades. This review will focus on identification and possible mechanisms of recently identified modifiers for muscular dystrophy, including osteopontin, latent TGFβ binding protein 4 (LTBP4) and Jagged1. Moreover, we will review the investigational approaches that aim to target modifier pathways and thereby counteract dystrophic muscle wasting.

  18. PSF reconstruction for AO photometry and astrometry

    NASA Astrophysics Data System (ADS)

    Ascenso, J.; Neichel, B.; Silva, M.; Fusco, T.; Garcia, P.

    2015-12-01

    Extracting accurate photometry (and astrometry) from images taken with adaptive optics assisted instruments is particularly challenging. Current post-processing tools are not prepared to achieve high accuracy from AO data, especially in limiting cases of crowded fields and marginally resolved sources. We quantify the limitations of these tools with synthetic images, and present a proof-of-concept study showing the potential of using reconstructed PSFs from the (GL)AO system telemetry to increase the measured photometric accuracy. We show that the photometric accuracy is significantly improved with a good PSF reconstruction in considerably crowded regions. We demonstrate the need for a dedicated post-processing tool that incorporates available information about the PSF, as well as the ability to adjust to the spatial variations of the PSF characteristic of AO data.

  19. Cardiac asynchrony in Duchenne muscular dystrophy.

    PubMed

    Fayssoil, Abdallah; Nardi, Olivier; Orlikowski, David; Annane, Djillali

    2013-10-01

    Duchenne muscular dystrophy (DMD) is an inherited myogenic disorder due to mutations in the dystrophin gene on chromosome Xp21.1. Heart failure is a classical complication in this disease. Little data are available about systolic dyssynchrony in DMD. We sought to assess the prevalence of left ventricular dysfunction and systolic asynchrony in DMD patients using echocardiographic parameters. We performed electrocardiography and echocardiography for adult's patients with DMD. For systolic dyssynchrony assessment, echocardiography-Doppler was performed and completed by tissular Doppler imaging. 48 DMD were included in our study. Age ranged from 20 to 37 years. QRS duration >120 ms was present in 10 patients/48 and 1 patient disclosed a QRS duration >150 ms. Left ventricular (LV) ejection fraction (EF) ranged from 10 to 62 % with a median of 43 %. Inter-ventricular asynchrony was found in 11.9 % of patients with EF < 35 % and in 2.6 % of patients with EF > 35 %. Intra-ventricular asynchrony was present in 6 % of patients with EF < 35 %. We found a high prevalence of LV dysfunction in DMD. Systolic ventricular asynchrony seems frequent particularly in patients with EF < 35 %.

  20. Optimizing Bone Health in Duchenne Muscular Dystrophy

    PubMed Central

    Buckner, Jason L.; Bowden, Sasigarn A.; Mahan, John D.

    2015-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by progressive muscle weakness, with eventual loss of ambulation and premature death. The approved therapy with corticosteroids improves muscle strength, prolongs ambulation, and maintains pulmonary function. However, the osteoporotic impact of chronic corticosteroid use further impairs the underlying reduced bone mass seen in DMD, leading to increased fragility fractures of long bones and vertebrae. These serious sequelae adversely affect quality of life and can impact survival. The current clinical issues relating to bone health and bone health screening methods in DMD are presented in this review. Diagnostic studies, including biochemical markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry (DXA), as well as spinal imaging using densitometric lateral spinal imaging, and treatment to optimize bone health in patients with DMD are discussed. Treatment with bisphosphonates offers a method to increase bone mass in these children; oral and intravenous bisphosphonates have been used successfully although treatment is typically reserved for children with fractures and/or bone pain with low bone mass by DXA. PMID:26124831

  1. Molecular diagnosis of Duchenne muscular dystrophy.

    PubMed

    Nallamilli, Babi Ramesh Reddy; Ankala, Arunkanth; Hegde, Madhuri

    2014-10-01

    Duchenne Muscular Dystrophy (DMD) is an X-linked inherited neuromuscular disorder caused by mutations in the dystrophin gene (DMD; locus Xp21.2). The mutation spectrum of DMD is unique in that 65% of causative mutations are intragenic deletions, with intragenic duplications and point mutations (along with other sequence variants) accounting for 6% to 10% and 30% to 35%, respectively. The strategy for molecular diagnostic testing for DMD involves initial screening for deletions/duplications using microarray-based comparative genomic hybridization (array-CGH) followed by full-sequence analysis of DMD for sequence variants. Recently, next-generation sequencing (NGS)-based targeted gene analysis has become clinically available for detection of point mutations and other sequence variants (small insertions, deletions, and indels). This unit initially discusses the strategic algorithm for establishing a molecular diagnosis of DMD and later provides detailed protocols of current molecular diagnostic methods for DMD, including array-CGH, PCR-based Sanger sequencing, and NGS-based sequencing assay.

  2. Lipomatous muscular 'dystrophy' of Piedmontese cattle.

    PubMed

    Biasibetti, E; Amedeo, S; Brugiapaglia, A; Destefanis, G; Di Stasio, L; Valenza, F; Capucchio, M T

    2012-11-01

    Lipomatous myopathy is a degenerative muscle pathology characterized by the substitution of muscle cells with adipose tissue, sporadically reported in cattle, pigs, and rarely in sheep, horses and dogs. This study investigated the pathology of this myopathy in 40 muscle samples collected from regularly slaughtered Piedmontese cattle living in Piedmont region (Italy). None of the animals showed clinical signs of muscular disease. Muscle specimens were submitted to histological and enzymatic investigations. Gross pathology revealed a different grade of infiltration of adipose tissue, involving multiple or single muscles. The most affected regions were the ventral abdomen and the shoulders, especially the cutaneous muscles and the muscles of the thoracic group. Morphological staining revealed an infiltration of adipose tissue varying in distribution and severity, changes in muscle fibre size and increased number of fibres with centrally located nuclei, suggesting muscle degeneration-regeneration. Necrosis and non-suppurative inflammatory cells were also seen. Furthermore, proliferation of connective tissue and non-specific myopathic changes were present. Chemical and physical characteristics of the affected tissue were also evaluated. The authors discuss about the aetiopathogenesis and classification of this muscle disorder whose histological lesions were similar to those reported in human dystrophies.

  3. Limb-girdle muscular dystrophy 2A.

    PubMed

    Gallardo, Eduard; Saenz, Amets; Illa, Isabel

    2011-01-01

    Limb-girdle muscular dystrophy type 2A (LGMD2A) is caused by mutations in the gene CAPN3 located in the chromosome region 15q15.1-q21.1. To date more than 300 mutations have been described. This gene encodes for a 94-kDa nonlysosomal calcium-dependent cysteine protease and its function in skeletal muscle is not fully understood. It seems that calpain-3 has an unusual zymogenic activation that involves, among other substrates, cytoskeletal proteins. Calpain-3 is thought to interact with titin and dysferlin. Calpain-3 deficiency produces abnormal sarcomeres that lead eventually to muscle fiber death. Hip adductors and gluteus maximus are the earliest clinically affected muscles. No clinical differences have been reported depending on the type of mutation in the CAPN3 gene. The muscle biopsy shows variability of fiber size, interstitial fibrosis, internal nuclei, lobulated fibers, and, in some cases, presence of eosinophils. Recent gene expression profiling studies have shown upregulation of interleukin-32 and immunoglobulin genes, which may explain the eosinophilic infiltration. Two mouse knockout models of CAPN3 have been characterized. There are no curative treatments for this disease. However, experimental therapeutics using mouse models conclude that adeno-associated virus (AAV) vectors seem to be one of the best approaches because of their efficiency and persistency of gene transfer.

  4. Throwing performance is associated with muscular power.

    PubMed

    Bourdin, M; Rambaud, O; Dorel, S; Lacour, J-R; Moyen, B; Rahmani, A

    2010-07-01

    The aim of the present study was to test the hypothesis that performance in throwing events is associated with muscular characteristics of both upper and lower limbs. Thirty-eight male throwers volunteered to participate. Bench press and half squat tests were conducted on a guided barbell. The barbell displacement signal was recorded using a kinematic system. Maximal power, corresponding optimal velocity and force (P(max)S, V(opt)S, F(opt)S and P(max)BP, V(opt)BP, F(opt)BP for half squat and bench press, respectively) were extrapolated from the power-velocity relationship. Lower limb stiffness (K) was determined during maximal hopping. The results demonstrated that P(max)S and P(max)BP were correlated with each thrower's season's best performance (SBP, R=0.54, P<0.01 and R=0.71, P<0.001, respectively). P(max)S expressed relative to body mass was not correlated with SBP. K was significantly correlated with SBP (R=0.66, P<0.001). The relationship between P (max)BP expressed relative to body mass and SBP remained significant ( R=0.54, P<0.001). The results of the study suggest that high strength and stiffness values for lower limbs and strength and velocity characteristics for upper limbs may be associated with athletic throwing performance.

  5. Spinal Muscular Atrophy: Current Therapeutic Strategies

    NASA Astrophysics Data System (ADS)

    Kiselyov, Alex S.; Gurney, Mark E.

    Proximal spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by death of motor neurons in the spinal cord. SMA is caused by deletion and/or mutation of the survival motor neuron gene (SMN1) on chromosome 5q13. There are variable numbers of copies of a second, related gene named SMN2 located in the proximity to SMN1. Both genes encode the same protein (Smn). Loss of SMN1 and incorrect splicing of SMN2 affect cellular levels of Smn triggering death of motor neurons. The severity of SMA is directly related to the normal number of copies of SMN2 carried by the patient. A considerable effort has been dedicated to identifying modalities including both biological and small molecule agents that increase SMN2 promoter activity to upregulate gene transcription and produce increased quantities of full-length Smn protein. This review summarizes recent progress in the area and suggests potential target product profile for an SMA therapeutic.

  6. Molecular analysis of facioscapulohumeral muscular dystrophy (FSHD)

    SciTech Connect

    Upadhyaya, M.; Maynard, J.; Osborn, M.

    1994-09-01

    Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder characterized by progressive muscle weakness. The disease locus maps to 4q35 and is associated with a de novo DNA rearrangement, detected by a probe p13E-11 (D4F104S1) which maps proximal to the disease locus. An informative distal flanking marker for this condition is still required. Using p13E-11, we have analyzed 35 FSHD families in which the disease is apparently associated with a new mutation. Twenty three of these cases were found to have a smaller rearranged DNA fragment which was not present in either of the parents. Pulsed-field gel analysis of 5 of these families also revealed evidence of DNA deletion. During the course of this study, we identified one case with a DNA rearrangement which was also present in the unaffected mother, but at very low intensity. This finding has been confirmed by pulsed-field gel analysis, and indicates that the mother is probably a gonosomal mosaic. In order to saturate the FSHD region with new DNA markers, a laser microdissection and microcloning technique was used to construct a genomic library from the distal end of chromosome 4. Of the 72 microclones analyzed, 42 mapped into the relevant 4q35 region. 4 sequences were conserved and may be considered potential candidate genes for FSHD. The microclones mapping to 4q35 are under study to identify additional polymorphic markers for the FSHD region.

  7. Twelve thousand laser-AO observations: first results from the Robo-AO large surveys

    NASA Astrophysics Data System (ADS)

    Law, Nicholas M.; Baranec, Christoph; Riddle, Reed L.

    2014-07-01

    Robo-AO is the first AO system which can feasibly perform surveys of thousands of targets. The system has been operating in a fully robotic mode on the Palomar 1.5m telescope for almost two years. Robo-AO has completed nearly 12,000 high-angular-resolution observations in almost 20 separate science programs including exoplanet characterization, field star binarity, young star binarity and solar system observations. We summarize the Robo-AO surveys and the observations completed to date. We also describe the data-reduction pipeline we developed for Robo-AO—the first fully-automated AO data-reduction, point-spread-function subtraction and companion-search pipeline.

  8. Muscular factors are of importance in tension-type headache.

    PubMed

    Jensen, R; Bendtsen, L; Olesen, J

    1998-01-01

    Recent studies have indicated that muscular disorders may be of importance for the development of increased pain sensitivity in patients with chronic tension-type headache. The objective of the present study was to investigate this hypothesis by examining the pain perception in tension-type headache with and without muscular disorders defined as increased tenderness. We examined 28 patients with episodic tension-type headache, 28 patients with chronic tension-type headache, and 30 healthy controls. Pericranial myofascial tenderness was recorded with manual palpation, and pressure pain detection and tolerances in cephalic and extracephalic locations with an electronic pressure algometer. In addition, thermal pain sensitivity and electromyographic activity were recorded. The main result was significantly lower pressure pain detection thresholds and tolerances in all the examined locations in patients with chronic tension-type headache with a muscular disorder compared to those without a muscular disorder. There were no such differences in any of the examined locations when the two subgroups of patients with episodic tension-type headache were compared. Thermal pain sensitivity did not differ between patients with and without a muscular disorder, while electromyographic activity levels were significantly higher in patients with chronic tension-type headache with than in those without a muscular disorder. Our results strongly indicate that prolonged nociceptive stimuli from the pericranial myofascial tissue sensitize the central nervous system and, thereby, lead to an increased general pain sensitivity. Muscular factors may, therefore, be of major importance for the conversion of episodic into chronic tension-type headache. The present study complements the understanding of the important interactions between peripheral and central factors in tension-type headache and may lead to a better prevention and treatment of the most prevalent type of headache.

  9. Characterization of an AO-OCT system

    SciTech Connect

    Evans, J W; Zawadzki, R J; Jones, S; Olivier, S; Werner, J S

    2007-07-26

    Adaptive optics (AO) and optical coherence tomography (OCT) are powerful imaging modalities that, when combined, can provide high-volumetric-resolution, images of the retina. The AO-OCT system at UC Davis has been under development for 2 years and has demonstrated the utility of this technology for microscopic, volumetric, in vivo retinal imaging [1]. The current system uses an AOptix bimorph deformable mirror (DM) for low-order, high-stroke correction [2] and a 140-actuator Boston Micromachines DM for high-order correction [3]. We are beginning to investigate the potential for increasing the image contrast in this system using higher-order wavefront correction. The first step in this analysis is to quantify the residual wavefront error (WFE) in the current system. Developing an error budget is a common tool for improved performance and system design in astronomical AO systems [4, 5]. The process for vision science systems is also discussed in several texts e.g. [6], but results from this type of analysis have rarely been included in journal articles on AO for vision science. Careful characterization of the AO system will lead to improved performance and inform the design of a future high-contrast system. In general, an AO system error budget must include an analysis of three categories of residual WFE: errors in measuring the phase, errors caused by limitations of the DM(s), and errors introduced by temporal variation. Understanding the mechanisms and relative size of these errors is critical to improving system performance. In this paper we discuss the techniques for characterizing these error sources in the AO-OCT system. It is useful to first calculate an error budget for the simpler case using a model eye, and then add the additional errors introduced for the case of a human subject. Measurement error includes calibration error, wavefront sensor (WFS) CCD noise, and sampling errors. Calibration errors must be measured by an external system. Typically this

  10. The burden of Duchenne muscular dystrophy

    PubMed Central

    Landfeldt, Erik; Lindgren, Peter; Bell, Christopher F.; Schmitt, Claude; Guglieri, Michela; Straub, Volker; Lochmüller, Hanns

    2014-01-01

    Objective: The objective of this study was to estimate the total cost of illness and economic burden of Duchenne muscular dystrophy (DMD). Methods: Patients with DMD from Germany, Italy, United Kingdom, and United States were identified through Translational Research in Europe–Assessment & Treatment of Neuromuscular Diseases registries and invited to complete a questionnaire online together with a caregiver. Data on health care use, quality of life, work status, informal care, and household expenses were collected to estimate costs of DMD from the perspective of society and caregiver households. Results: A total of 770 patients (173 German, 122 Italian, 191 from the United Kingdom, and 284 from the United States) completed the questionnaire. Mean per-patient annual direct cost of illness was estimated at between $23,920 and $54,270 (2012 international dollars), 7 to 16 times higher than the mean per-capita health expenditure in these countries. Indirect and informal care costs were substantial, each constituting between 18% and 43% of total costs. The total societal burden was estimated at between $80,120 and $120,910 per patient and annum, and increased markedly with disease progression. The corresponding household burden was estimated at between $58,440 and $71,900. Conclusions: We show that DMD is associated with a substantial economic burden. Our results underscore the many different costs accompanying a rare condition such as DMD and the considerable economic burden carried by affected families. Our description of the previously unknown economic context of a rare disease serves as important intelligence input to health policy evaluations of intervention programs and novel therapies, financial support schemes for patients and their families, and the design of future cost studies. PMID:24991029

  11. Modeling Spinal Muscular Atrophy in Drosophila

    PubMed Central

    Mukherjee, Ashim; Kankel, Mark W.; Sen, Anindya; Sridhar, Vasanthi; Fulga, Tudor A.; Hart, Anne C.; Van Vactor, David; Artavanis-Tsakonas, Spyros

    2008-01-01

    Spinal Muscular Atrophy (SMA), a recessive hereditary neurodegenerative disease in humans, has been linked to mutations in the survival motor neuron (SMN) gene. SMA patients display early onset lethality coupled with motor neuron loss and skeletal muscle atrophy. We used Drosophila, which encodes a single SMN ortholog, survival motor neuron (Smn), to model SMA, since reduction of Smn function leads to defects that mimic the SMA pathology in humans. Here we show that a normal neuromuscular junction (NMJ) structure depends on SMN expression and that SMN concentrates in the post-synaptic NMJ regions. We conducted a screen for genetic modifiers of an Smn phenotype using the Exelixis collection of transposon-induced mutations, which affects approximately 50% of the Drosophila genome. This screen resulted in the recovery of 27 modifiers, thereby expanding the genetic circuitry of Smn to include several genes not previously known to be associated with this locus. Among the identified modifiers was wishful thinking (wit), a type II BMP receptor, which was shown to alter the Smn NMJ phenotype. Further characterization of two additional members of the BMP signaling pathway, Mothers against dpp (Mad) and Daughters against dpp (Dad), also modify the Smn NMJ phenotype. The NMJ defects caused by loss of Smn function can be ameliorated by increasing BMP signals, suggesting that increased BMP activity in SMA patients may help to alleviate symptoms of the disease. These results confirm that our genetic approach is likely to identify bona fide modulators of SMN activity, especially regarding its role at the neuromuscular junction, and as a consequence, may identify putative SMA therapeutic targets. PMID:18791638

  12. Duchenne Muscular Dystrophy: From Diagnosis to Therapy.

    PubMed

    Falzarano, Maria Sofia; Scotton, Chiara; Passarelli, Chiara; Ferlini, Alessandra

    2015-10-07

    Duchenne muscular dystrophy (DMD) is an X-linked inherited neuromuscular disorder due to mutations in the dystrophin gene. It is characterized by progressive muscle weakness and wasting due to the absence of dystrophin protein that causes degeneration of skeletal and cardiac muscle. The molecular diagnostic of DMD involves a deletions/duplications analysis performed by quantitative technique such as microarray-based comparative genomic hybridization (array-CGH), Multiple Ligation Probe Assay MLPA. Since traditional methods for detection of point mutations and other sequence variants require high cost and are time consuming, especially for a large gene like dystrophin, the use of next-generation sequencing (NGS) has become a useful tool available for clinical diagnosis. The dystrophin gene is large and finely regulated in terms of tissue expression, and RNA processing and editing includes a variety of fine tuned processes. At present, there are no effective treatments and the steroids are the only fully approved drugs used in DMD therapy able to slow disease progression. In the last years, an increasing variety of strategies have been studied as a possible therapeutic approach aimed to restore dystrophin production and to preserve muscle mass, ameliorating the DMD phenotype. RNA is the most studied target for the development of clinical strategies and Antisense Oligonucleotides (AONs) are the most used molecules for RNA modulation. The identification of delivery system to enhance the efficacy and to reduce the toxicity of AON is the main purpose in this area and nanomaterials are a very promising model as DNA/RNA molecules vectors. Dystrophinopathies therefore represent a pivotal field of investigation, which has opened novel avenues in molecular biology, medical genetics and novel therapeutic options.

  13. Neuropsychological profile of duchenne muscular dystrophy.

    PubMed

    Perumal, Anna Roshini; Rajeswaran, Jamuna; Nalini, Atchayaram

    2015-01-01

    Duchenne muscular dystrophy (DMD) is an inherited myogenic disorder characterized by progressive muscle wasting. DMD is a fatal X-linked recessive disorder with an estimated prevalence of 1 in 3,500 male live births. This disease has long been associated with intellectual impairment. Research has shown that boys with DMD have variable intellectual performance, indicating the presence of specific cognitive deficits. The aim of the study was to use a battery of intelligence, learning, and memory tests to identify a neuropsychological profile in boys with DMD. A total of 22 boys diagnosed with DMD in the age range of 6 to 10 years old were evaluated using the Wechsler Intelligence Scale for Children-Third Edition, Rey's Auditory Verbal Learning Test, and the Memory for Designs Test. The data were interpreted using means, standard deviations, percentages, and percentiles. Normative data were also used for further interpretation. The results showed that boys with DMD had a significantly lower IQ (88.5). Verbal IQ (86.59) was found to be lower than Performance IQ (92.64). There was evidence of impaired performance on the Processing Speed, Freedom From Distractibility, and Verbal Comprehension Indexes. Specific deficits in information processing, complex attention, immediate verbal memory span, verbal working memory, verbal comprehension, vocabulary, visuoconstruction ability, and verbal learning and encoding were observed. However, perceptional organization, general fund of information, abstract reasoning, visual discrimination and acuity, visual learning and memory, and verbal memory were adequate. The neuropsychological findings support the hypothesis that these children have specific cognitive deficits as opposed to a global intellectual deficit.

  14. Neurocognitive Profiles in Duchenne Muscular Dystrophy and Gene Mutation Site

    PubMed Central

    D’Angelo, Maria Grazia; Lorusso, Maria Luisa; Civati, Federica; Comi, Giacomo Pietro; Magri, Francesca; Del Bo, Roberto; Guglieri, Michela; Molteni, Massimo; Turconi, Anna Carla; Bresolin, Nereo

    2011-01-01

    The presence of nonprogressive cognitive impairment is recognized as a common feature in a substantial proportion of patients with Duchenne muscular dystrophy. To investigate the possible role of mutations along the dystrophin gene affecting different brain dystrophin isoforms and specific cognitive profiles, 42 school-age children affected with Duchenne muscular dystrophy, subdivided according to sites of mutations along the dystrophin gene, underwent a battery of tests tapping a wide range of intellectual, linguistic, and neuropsychologic functions. Full-scale intelligence quotient was approximately 1 S.D. below the population average in the whole group of dystrophic children. Patients with Duchenne muscular dystrophy and mutations located in the distal portion of the dystrophin gene (involving the 140-kDa brain protein isoform, called Dp140) were generally more severely affected and expressed different patterns of strengths and impairments, compared with patients with Duchenne muscular dystrophy and mutations located in the proximal portion of the dystrophin gene (not involving Dp140). Patients with Duchenne muscular dystrophy and distal mutations demonstrated specific impairments in visuospatial functions and visual memory (which seemed intact in proximally mutated patients) and greater impairment in syntactic processing. PMID:22000308

  15. Intrathecal Injections in Children With Spinal Muscular Atrophy

    PubMed Central

    Swoboda, Kathryn J.; Sethna, Navil; Farrow-Gillespie, Alan; Khandji, Alexander; Xia, Shuting; Bishop, Kathie M.

    2016-01-01

    Nusinersen (ISIS-SMNRx or ISIS 396443) is an antisense oligonucleotide drug administered intrathecally to treat spinal muscular atrophy. We summarize lumbar puncture experience in children with spinal muscular atrophy during a phase 1 open-label study of nusinersen and its extension. During the studies, 73 lumbar punctures were performed in 28 patients 2 to 14 years of age with type 2/3 spinal muscular atrophy. No complications occurred in 50 (68%) lumbar punctures; in 23 (32%) procedures, adverse events were attributed to lumbar puncture. Most common adverse events were headache (n = 9), back pain (n = 9), and post–lumbar puncture syndrome (n = 8). In a subgroup analysis, adverse events were more frequent in older children, children with type 3 spinal muscular atrophy, and with a 21- or 22-gauge needle compared to a 24-gauge needle or smaller. Lumbar punctures were successfully performed in children with spinal muscular atrophy; lumbar puncture–related adverse event frequency was similar to that previously reported in children. PMID:26823478

  16. Congenital segmental spinal muscular atrophy: a case report.

    PubMed

    Savaş, Tülin; Erol, Ilknur; Özkale, Yasemin; Saygi, Semra

    2015-03-01

    Spinal muscular atrophies are genetic disorders in which anterior horn cells in the spinal cord and motor nuclei of the brainstem are progressively lost. We present a patient with arthrogryposis due to congenital spinal muscular atrophy predominantly affecting the upper limbs. Spinal muscular atrophies with onset at birth may be a cause of arthrogryposis. Localized forms of neurogenic arthrogryposis have been divided into cervical and caudal forms. Our case is similar to the cases described by Hageman et al (J Neurol Neurosurg Psychiatry 1993;56:365-368): severe symmetric lower motor neuron deficit in the upper extremities at the time of birth, no history of injury to the cervical spinal cord or the brachial plexus during delivery, and severe muscle wasting suggesting chronic denervation in utero. Because there was improvement of our patient's situation, her disease was also possibly nonprogressive and sporadic. To our knowledge, this is the first reported case of a Turkish patient with congenital cervical spinal muscular atrophy. Congenital cervical spinal muscular atrophy affecting predominantly the upper limbs is a relatively rare form of motor neuron disease and should be considered in the differential diagnosis of infants with congenital contractures and severe muscle weakness by wasting mainly confined to the upper limbs.

  17. Inhibition of Prostaglandin D Synthase Suppresses Muscular Necrosis

    PubMed Central

    Mohri, Ikuko; Aritake, Kosuke; Taniguchi, Hidetoshi; Sato, Yo; Kamauchi, Shinya; Nagata, Nanae; Maruyama, Toshihiko; Taniike, Masako; Urade, Yoshihiro

    2009-01-01

    Duchenne muscular dystrophy is a fatal muscle wasting disease that is characterized by a deficiency in the protein dystrophin. Previously, we reported that the expression of hematopoietic prostaglandin D synthase (HPGDS) appeared in necrotic muscle fibers from patients with either Duchenne muscular dystrophy or polymyositis. HPGDS is responsible for the production of the inflammatory mediator, prostaglandin D2. In this paper, we validated the hypothesis that HPGDS has a role in the etiology of muscular necrosis. We investigated the expression of HPGDS/ prostaglandin D2 signaling using two different mouse models of muscle necrosis, that is, bupivacaine-induced muscle necrosis and the mdx mouse, which has a genetic muscular dystrophy. We treated each mouse model with the HPGDS-specific inhibitor, HQL-79, and measured both necrotic muscle volume and selected cytokine mRNA levels. We confirmed that HPGDS expression was induced in necrotic muscle fibers in both bupivacaine-injected muscle and mdx mice. After administration of HQL-79, necrotic muscle volume was significantly decreased in both mouse models. Additionally, mRNA levels of both CD11b and transforming growth factor β1 were significantly lower in HQL-79-treated mdx mice than in vehicle-treated animals. We also demonstrated that HQL-79 suppressed prostaglandin D2 production and improved muscle strength in the mdx mouse. Our results show that HPGDS augments inflammation, which is followed by muscle injury. Furthermore, the inhibition of HPGDS ameliorates muscle necrosis even in cases of genetic muscular dystrophy. PMID:19359520

  18. Muscular activity and its relationship to biomechanics and human performance

    NASA Technical Reports Server (NTRS)

    Ariel, Gideon

    1994-01-01

    The purpose of this manuscript is to address the issue of muscular activity, human motion, fitness, and exercise. Human activity is reviewed from the historical perspective as well as from the basics of muscular contraction, nervous system controls, mechanics, and biomechanical considerations. In addition, attention has been given to some of the principles involved in developing muscular adaptations through strength development. Brief descriptions and findings from a few studies are included. These experiments were conducted in order to investigate muscular adaptation to various exercise regimens. Different theories of strength development were studied and correlated to daily human movements. All measurement tools used represent state of the art exercise equipment and movement analysis. The information presented here is only a small attempt to understand the effects of exercise and conditioning on Earth with the objective of leading to greater knowledge concerning human responses during spaceflight. What makes life from nonliving objects is movement which is generated and controlled by biochemical substances. In mammals. the controlled activators are skeletal muscles and this muscular action is an integral process composed of mechanical, chemical, and neurological processes resulting in voluntary and involuntary motions. The scope of this discussion is limited to voluntary motion.

  19. TRIM proteins in therapeutic membrane repair of muscular dystrophy.

    PubMed

    Alloush, Jenna; Weisleder, Noah

    2013-07-01

    Muscular dystrophy represents a major unmet medical need; only palliative treatments exist for this group of debilitating diseases. Because multiple forms of muscular dystrophy arise from compromised sarcolemmal membrane integrity, a therapeutic approach that can target this loss of membrane function could be applicable to a number of these distinct diseases.One promising therapeutic approach involves the process the cell uses to repair injuries to the plasma membrane. Recent discoveries of genes associated with the membrane repair process provide an opportunity to promote this process as a way to treat muscular dystrophy. One such gene is mitsugumin 53 (MG53), a member of the tripartite motif (TRIM) family of proteins (TRIM72), which is an essential component of the membrane repair pathway in muscle. Recent results indicate that MG53/TRIM72 protein can be directly applied as a therapeutic agent to increase membrane repair capacity of many cell types and treat some aspects of the disease in mouse models of muscular dystrophy. There is great potential for the use of recombinant human MG53 in treating muscular dystrophy and other diseases in which compromised membrane integrity contributes to the disease. Other TRIM family proteins may provide additional targets for therapeutic intervention in similar disease states.

  20. Muscular, skeletal, and neural adaptations following spinal cord injury.

    PubMed

    Shields, Richard K

    2002-02-01

    Spinal cord injury is associated with adaptations to the muscular, skeletal, and spinal systems. Experimental data are lacking regarding the extent to which rehabilitative methods may influence these adaptations. An understanding of the plasticity of the muscular, skeletal, and spinal systems after paralysis may be important as new rehabilitative technologies emerge in the 21st century. Moreover, individuals injured today may become poor candidates for future scientific advancements (cure) if their neuromusculoskeletal systems are irreversibly impaired. The primary purpose of this paper is to explore the physiological properties of skeletal muscle as a result of spinal cord injury; secondarily, to consider associated changes at the skeletal and spinal levels. Muscular adaptations include a transformation to faster myosin, increased contractile speeds, shift to the right on the torque-frequency curve, increased fatigue, and enhanced doublet potentiation. These muscular adaptations may be prevented in individuals with acute paralysis and partially reversed in individuals with chronic paralysis. Moreover, the muscular changes may be coordinated with motor unit and spinal circuitry adaptations. Concurrently, skeletal adaptations, as measured by bone mineral density, show extensive loss within the first six months after paralysis. The underlying science governing neuromusculoskeletal adaptations after paralysis will help guide professionals as new rehabilitation strategies evolve in the future.

  1. Psychometric properties of Yelland and Tiggemann's Drive for Muscularity Scale.

    PubMed

    Tod, David; Morrison, Todd G; Edwards, Christian

    2012-06-01

    The purpose of the current study was to examine the dimensionality and validity of Yelland and Tiggemann's Drive for Muscularity Scale (YT-DMS). Participants were college students (305 women, M(AGE)=20.15 years, SD=4.00; 356 men, M(AGE)=20.24 years, SD=3.85) who completed the YT-DMS, the Drive for Muscularity Attitudes Questionnaire, the Drive for Leanness Scale, the Drive for Thinness Scale, and a socio-demographic questionnaire. Results indicated the YT-DMS had a stable unidimensional factor structure in both genders, and the pattern of relationships generally supported the measure's criterion and construct validity. These results reveal the YT-DMS has promise, but helps identify possible areas for improvement, such as a greater focus on sampling the content domain associated with the drive for muscularity.

  2. Psychosocial predictors of drive for muscularity in male collegiate athletes.

    PubMed

    Galli, Nick; Petrie, Trent; Reel, Justine J; Greenleaf, Christy; Carter, Jennifer E

    2015-06-01

    The purpose of this study was to examine the simultaneous relation of general and sport-specific pressures about body weight and shape, negative affect, and body satisfaction to drive for muscularity (DM) in male collegiate athletes. Participants were 183 male athletes who were drawn from three NCAA Division I institutions and represented 17 different sports. As hypothesized, after controlling for BMI and sport type, sport-specific pressures, negative affect, and body satisfaction were significant predictors, and accounted for 15-34% of the variance in muscularity-oriented body image and muscularity behaviors; general pressures however were not significantly related. These findings offer insight into the personal and social antecedents of DM in male athletes, and serve as a starting point for future research on DM in this population.

  3. Recapitulation of developing artery muscularization in pulmonary hypertension.

    PubMed

    Sheikh, Abdul Q; Lighthouse, Janet K; Greif, Daniel M

    2014-03-13

    Excess smooth muscle accumulation is a key component of many vascular disorders, including atherosclerosis, restenosis, and pulmonary artery hypertension, but the underlying cell biological processes are not well defined. In pulmonary artery hypertension, reduced pulmonary artery compliance is a strong independent predictor of mortality, and pathological distal arteriole muscularization contributes to this reduced compliance. We recently demonstrated that embryonic pulmonary artery wall morphogenesis consists of discrete developmentally regulated steps. In contrast, poor understanding of distal arteriole muscularization in pulmonary artery hypertension severely limits existing therapies that aim to dilate the pulmonary vasculature but have modest clinical benefit and do not prevent hypermuscularization. Here, we show that most pathological distal arteriole smooth muscle cells, but not alveolar myofibroblasts, derive from pre-existing smooth muscle. Furthermore, the program of distal arteriole muscularization encompasses smooth muscle cell dedifferentiation, distal migration, proliferation, and then redifferentiation, thereby recapitulating many facets of arterial wall development.

  4. Cognitive and Neurobehavioral Profile in Boys With Duchenne Muscular Dystrophy.

    PubMed

    Banihani, Rudaina; Smile, Sharon; Yoon, Grace; Dupuis, Annie; Mosleh, Maureen; Snider, Andrea; McAdam, Laura

    2015-10-01

    Duchenne muscular dystrophy is a progressive neuromuscular condition that has a high rate of cognitive and learning disabilities as well as neurobehavioral disorders, some of which have been associated with disruption of dystrophin isoforms. Retrospective cohort of 59 boys investigated the cognitive and neurobehavioral profile of boys with Duchenne muscular dystrophy. Full-scale IQ of < 70 was seen in 27%; learning disability in 44%, intellectual disability in 19%; attention-deficit/hyperactivity disorder in 32%; autism spectrum disorders in 15%; and anxiety in 27%. Mutations affecting Dp260 isoform and 5'untranslated region of Dp140 were observed in 60% with learning disability, 50% intellectual disability, 77% with autism spectrum disorders, and 94% with anxiety. No statistically significant correlation was noted between comorbidities and dystrophin isoforms; however, there is a trend of cumulative loss of dystrophin isoforms with declining full-scale IQ. Enhanced psychology testing to include both cognitive and neurobehavioral disorders is recommended for all individuals with Duchenne muscular dystrophy.

  5. Effects of yoga practice on muscular endurance in young women.

    PubMed

    Shiraishi, Juliana Costa; Bezerra, Lídia Mara Aguiar

    2016-02-01

    The aim of this study was to verify the effects of a systematized yoga practice on muscular endurance in young women. Twenty six women (24 ± 3.5 years old) participated in six weeks of yoga classes, and twenty one women (25 ± 5.1 years old) participated as the control group. The yoga intervention was composed of eighteen sessions, three times per week, at 1 h per session. The muscular endurance of upper limbs (push-up) and abdominal (sit-up) was assessed through the protocol suggested by Gettman (1989) [1] and Golding, Myers and Sinning (1989) [2] to the maximum repetitions performed in 1 min. To verify the significant differences intra groups and between groups a SPANOVA was performed, and the level of significance was p ≤ 0.05. The findings suggest that yoga provides improvement in upper limb and in abdominal muscular endurance.

  6. Respiratory surveillance of patients with Duchenne and Becker muscular dystrophy.

    PubMed

    Spehrs-Ciaffi, Virginia; Fitting, Jean William; Cotting, Jacques; Jeannet, Pierre-Yves

    2009-01-01

    Duchenne muscular dystrophy is is the most common form of the childhood muscular dystrophies. It follows a predictable clinical course marked by progressive skeletal muscle weakness, lost of ambulation before teen-age and death in early adulthood secondary to respiratory or cardiac failure. Becker muscular dystrophy is less common and has a milder clinical course but also results in respiratory and cardiac failure.Altough recent advances in respiratory care and new technologies have improved the outlook many patients already received only a traditional non-interventional approach. The aims of this work are: to analyse the pathophysiology and natural history of respiratory function in these diseases, to descript their clinical manifestations, to present the diagnostics tools and to provide recommendations for an adequated respiratory care in this particular population based on the updated literature referenced.

  7. Gene therapy for muscular dystrophy: moving the field forward.

    PubMed

    Al-Zaidy, Samiah; Rodino-Klapac, Louise; Mendell, Jerry R

    2014-11-01

    Gene therapy for the muscular dystrophies has evolved as a promising treatment for this progressive group of disorders. Although corticosteroids and/or supportive treatments remain the standard of care for Duchenne muscular dystrophy, loss of ambulation, respiratory failure, and compromised cardiac function is the inevitable outcome. Recent developments in genetically mediated therapies have allowed for personalized treatments that strategically target individual muscular dystrophy subtypes based on disease pathomechanism and phenotype. In this review, we highlight the therapeutic progress with emphasis on evolving preclinical data and our own experience in completed clinical trials and others currently underway. We also discuss the lessons we have learned along the way and the strategies developed to overcome limitations and obstacles in this field.

  8. Preclinical studies for gene therapy of Duchenne muscular dystrophy.

    PubMed

    Odom, Guy L; Banks, Glen B; Schultz, Brian R; Gregorevic, Paul; Chamberlain, Jeffrey S

    2010-09-01

    The muscular dystrophies are a diverse group of genetic disorders without an effective treatment. Because they are caused by mutations in various genes, the most direct way to treat them involves correcting the underlying gene defect (ie, gene therapy). Such a gene therapy approach involves delivering a therapeutic gene cassette to essentially all the muscles of the body in a safe and efficacious manner. The authors describe gene delivery methods using vectors derived from adeno-associated virus that are showing great promise in preclinical studies for treatment of Duchenne muscular dystrophy. It is hoped that variations on these methods might be applicable for most, if not all, of the different types of muscular dystrophy.

  9. Evaluation of muscular stabilization ability during a static workout.

    PubMed

    Staniszewski, Michał; Urbanik, Czesław; Staniszewski, Tadeusz

    2010-01-01

    The aim of this research was to determine the moving and stabilizing functions of selected groups of muscles during the process of static workout. 15 students of the Academy of Physical Education were tested in non-competitive training. Muscular torques achieved during flexing and extending big limb joints were used as the determinant of force. Comparative analysis of torque values achieved in passive stabilization (with support) and muscular stabilization (without support) in elbow and knee joints was carried out. The value of the force applied to the passively stabilizing element in a given measurement during the flexion of elbow and the extension of knee joint was tested. The results of these tests allowed us to learn the value of muscular torques and - after statistical analysis - the relationship between them in particular functions.

  10. Idiopathic intracranial hypertension in a child with Duchenne muscular dystrophy.

    PubMed

    Weig, Spencer G; Zinn, Matthias M; Howard, James F

    2011-12-01

    Duchenne muscular dystrophy is an X-linked, recessively inherited disorder characterized by progressive weakness attributable to the absence of dystrophin expression in muscle. In multiple studies, the chronic administration of corticosteroids slowed the loss of ambulation that develops in mid to late childhood. Corticosteroids, however, frequently produce unacceptable side effects, including Cushingoid appearance and weight gain. Deflazacort, an oxazoline analogue of prednisolone, produces equivalent benefits on muscle with fewer reported Cushingoid side effects. We present a 9-year-old boy with Duchenne muscular dystrophy who developed morbid obesity and subsequent idiopathic intracranial hypertension after 2 years of receiving deflazacort. Although deflazacort is typically thought to produce less obesity than prednisone, severe Cushingoid side effects may occur in some individuals. To our knowledge, this description is the first of idiopathic intracranial hypertension complicating chronic corticosteroid treatment of Duchenne muscular dystrophy.

  11. Pharmacologic and genetic therapy for childhood muscular dystrophies.

    PubMed

    Escolar, D M; Scacheri, C G

    2001-03-01

    The outstanding advances in the molecular characterization of muscle diseases, including muscular dystrophies, inflammatory myopathies, and ion channel disorders, have resulted in the identification of potential targets for pharmacologic and genetic therapy in the best characterized of these diseases. The most common myopathy in children, Duchenne muscular dystrophy (DMD), is the focus of active pharmacologic clinical trials. Genetic transfer therapy research for this and other dystrophies is rapidly moving forward. However, as new approaches for treatment are being actively investigated, the current modality of treatment for all myopathies is still in the realm of physical medicine and rehabilitation. The focus of this review is on the advances in pharmacologic and genetic therapy research in DMD and limb girdle muscular dystrophies.

  12. Jagged 1 rescues the Duchenne muscular dystrophy phenotype

    PubMed Central

    Vieira, Natassia M.; Elvers, Ingegerd; Alexander, Matthew S.; Moreira, Yuri B.; Eran, Alal; Gomes, Juliana P.; Marshall, Jamie L.; Karlsson, Elinor K.; Verjovski-Almeida, Sergio; Lindblad-Toh, Kerstin; Kunkel, Louis M.; Zatz, Mayana

    2015-01-01

    Summary Duchenne muscular dystrophy, caused by mutations at the dystrophin gene, is the most common form of Muscular Dystrophy. There is no cure for DMD and current therapeutic approaches to restore dystrophin expression are only partially effective. The absence of dystrophin in muscle results in dysregulation of signaling pathways which could be targets for disease therapy and drug discovery. Previously we identified two exceptional Golden Retriever Muscular Dystrophy (GRMD) dogs that are mildly affected, have functional muscle and normal lifespan despite the complete absence of dystrophin. Now, our data on linkage, whole genome sequencing and transcriptome analyses of these dogs compared to severely affected GRMD and control animals reveal that increased expression of Jagged1 gene, a known regulator of the Notch signaling pathway, is a hallmark of the mild phenotype. Functional analyses demonstrate that Jagged1 overexpression ameliorates the dystrophic phenotype, suggesting that Jagged1 may represent a target for DMD therapy in a dystrophin-independent manner. PMID:26582133

  13. MEMS DM development at Iris AO, Inc.

    NASA Astrophysics Data System (ADS)

    Helmbrecht, Michael A.; He, Min; Kempf, Carl J.; Besse, Marc

    2011-03-01

    Iris AO is actively developing piston-tip-tilt (PTT) segmented MEMS deformable mirrors (DM) and adaptive optics (AO) controllers for these DMs. This paper discusses ongoing research at Iris AO that has advanced the state-of-the-art of these devices and systems over the past year. Improvements made to open-loop operation and mirror fabrication enables mirrors to open-loop flatten to 4 nm rms. Additional testing of an anti snap-in technology was conducted and demonstrates that the technology can withstand 100 million snap-in events without failure. Deformable mirrors with dielectric coatings are shown that are capable of handling 630 W/cm2 of incident laser power. Over a localized region on the segment, the dielectric coatings can withstand 100kW/cm2 incident laser power for 30 minutes. Results from the first-ever batch of PTT489 DMs that were shipped to pilot customers are reported. Optimizations made to the open-loop PTT controller are shown to have latencies of 157.5 μs and synchronous array update rates of nearly 6.5 kHz. Finally, plans for the design and fabrication of the next-generation PTT939 DM are presented.

  14. Structural deterioration of tendon collagen in genetic muscular dystrophy.

    PubMed

    Stinson, R H

    1975-08-19

    The structure of gastrocnemius tendons from chickens with genetically induced muscular dystrophy has been studied by low-angle X-ray diffraction. Compared with normal samples there is poor alignment of collagen within the tendons. This difference is quite pronounced at eight weeks when the affected birds are still in comparatively good physical condition. Similar changes have been reported for birds with nutritionally induced muscular dystrophy (Bartlett, M. W., Egelstaff, P. A., Holden, T. M., Stinson, R. H. and Sweeny, P. R. (1973) Biochim. Biophys. Acta 328, 213-220).

  15. Congenital contractural arachnodactyly with neurogenic muscular atrophy: case report.

    PubMed

    Scola, R H; Werneck, L C; Iwamoto, F M; Ribas, L C; Raskin, S; Correa Neto, Y

    2001-06-01

    We report the case of a 3-(1/2)-year-old girl with hypotonia, multiple joint contractures, hip luxation, arachnodactyly, adducted thumbs, dolichostenomelia, and abnormal external ears suggesting the diagnosis of congenital contractural arachnodactyly (CCA). The serum muscle enzymes were normal and the needle electromyography showed active and chronic denervation. The muscle biopsy demonstrated active and chronic denervation compatible with spinal muscular atrophy. Analysis of exons 7 and 8 of survival motor neuron gene through polymerase chain reaction did not show deletions. Neurogenic muscular atrophy is a new abnormality associated with CCA, suggesting that CCA is clinically heterogeneous.

  16. The paradox of muscle hypertrophy in muscular dystrophy.

    PubMed

    Kornegay, Joe N; Childers, Martin K; Bogan, Daniel J; Bogan, Janet R; Nghiem, Peter; Wang, Jiahui; Fan, Zheng; Howard, James F; Schatzberg, Scott J; Dow, Jennifer L; Grange, Robert W; Styner, Martin A; Hoffman, Eric P; Wagner, Kathryn R

    2012-02-01

    Mutations in the dystrophin gene cause Duchenne and Becker muscular dystrophy in humans and syndromes in mice, dogs, and cats. Affected humans and dogs have progressive disease that leads primarily to muscle atrophy. Mdx mice progress through an initial phase of muscle hypertrophy followed by atrophy. Cats have persistent muscle hypertrophy. Hypertrophy in humans has been attributed to deposition of fat and connective tissue (pseudohypertrophy). Increased muscle mass (true hypertrophy) has been documented in animal models. Muscle hypertrophy can exaggerate postural instability and joint contractures. Deleterious consequences of muscle hypertrophy should be considered when developing treatments for muscular dystrophy.

  17. An Exploration of the Drive for Muscularity in Adolescent Boys and Girls.

    ERIC Educational Resources Information Center

    McCreary, Donald R.; Sasse, Doris K.

    2000-01-01

    Investigated the drive for muscularity among high school adolescents using the Drive for Muscularity Scale. Results indicated that the scale was reliable. High-drive students were mainly boys trying to gain weight and muscle mass. Drive related to poor self-esteem and higher depression levels among boys, but not girls. Drive for muscularity was…

  18. Be careful about abdominal discomfort in adult patients with muscular dystrophy.

    PubMed

    Fayssoil, A; Ritzenthaler, T; Luis, D; Hullin, T; Clair, B; Annane, D; Orlikowski, D

    2014-01-01

    Muscular dystrophies are genetic muscular disease with disability. Heart failure is a classical complication mainly in Duchenne muscular dystrophy (DMD). We report 2 cases of severe acute heart failure revealed by abdominal discomfort in a patient with DMD and in a patient with gamma-sarcoglycanopathy.

  19. Molecular genetics of facioscapulohumeral muscular dystrophy (FSHD).

    PubMed

    Fisher, J; Upadhyaya, M

    1997-01-01

    Facioscapulohumeral muscular dystrophy (FSHD; MIM 158900), is an autosomal dominant neuromuscular disorder. The disease is characterized by the weakness of the muscles of the face, upper-arm and shoulder girdle. The gene for FSHD has been mapped to 4q35 (FSHD1A) and is closely linked to D4F1O4S1, which detects two highly polymorphic loci (located at 4q35 and 10q26), with restriction enzyme EcoRI. The polymorphic EcoRI fragment detected with D4F1O4S1 is composed almost entirely of D4Z4 (3.3 kb) tandem repeats. In FSHD patients a deletion of the integral number of D4Z4 repeats generates a fragment which is usually smaller than 35 kb, whereas in normal controls, the size usually ranges from 50 to 300 kb. These 'small' EcoRI fragments segregate with FSHD in families but appear as de novo deletions in the majority of sporadic cases. Each 3.3 kb repeat contains two homeobox domains neither of which has yet been proven to encode a protein. D4Z4 is located adjacent to the 4q telomere and cross hybridizes to several different regions of the genome. Although D4Z4 probably does not encode a protein with any direct association to FSHD, a clear correlation has been shown between the deletion size at this locus and the age at onset of the disease in FSHD patients. In approximately 5-10% of FSHD families the disease locus is unlinked to 4q35 (locus designated FSHD1B), however, none of the non 4q35 loci for FSHD have yet been chromosomally located. Thus so far, only one gene, FRG1 (FSHD region gene 1) has been identified from the FSHD candidate region on 4q35. The apparent low level of expressed sequences from within this region, the integral deletions of D4Z4 repeats observed in FSHD patients and the close proximity of these repeats to the 4q telomere, all suggest that the disease may be the result of position effect variegation. To date, the molecular diagnosis of FSHD with D4F104S1 has been most secure in those families which are linked to other 4q35 markers. Recent studies

  20. Drive for muscularity and muscularity-oriented disordered eating in men: the role of set shifting difficulties and weak central coherence.

    PubMed

    Griffiths, Scott; Murray, Stuart B; Touyz, Stephen

    2013-09-01

    Set shifting difficulties and weak central coherence are information-processing biases associated with thinness-oriented eating and body image pathology in women. However, little is known about the relationship between these processing biases and muscularity-oriented eating and body image pathology. We investigated whether set shifting and central coherence were uniquely related to the drive for muscularity and muscularity-oriented disordered eating in a sample of 91 male undergraduates. Participants completed the Wisconsin Card Sort Test, the Matching Familiar Figures Task, the Drive for Muscularity scale, and a modified Eating Disorders Examination-Questionnaire. Results indicated that set shifting difficulties and weak central coherence were both uniquely positively associated with the drive for muscularity, and that set shifting difficulties were uniquely positively associated with muscularity-oriented disordered eating. Results are discussed with regard to the male experience of body image and eating pathology, and in regard to muscle dysmorphia.

  1. Cardiomyopathy in Duchenne muscular dystrophy: pathogenesis and therapeutics.

    PubMed

    Fayssoil, Abdallah; Nardi, Olivier; Orlikowski, David; Annane, Djillali

    2010-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by the absence of dystrophin, a sarcolemmal protein which links the cytoskeleton to the extracellular matrix by interacting with a large number of proteins. Heart failure is a classic complication of this disease. The authors review the pathogenesis and therapeutics of cardiac involvement in DMD.

  2. Neural Issues in the Control of Muscular Strength

    ERIC Educational Resources Information Center

    Kamen, Gary

    2004-01-01

    During the earliest stages of resistance exercise training, initial muscular strength gains occur too rapidly to be explained solely by muscle-based mechanisms. However, increases in surface-based EMG amplitude as well as motor unit discharge rate provide some insight to the existence of neural mechanisms in the earliest phases of resistance…

  3. Instructions to Adopt an External Focus Enhance Muscular Endurance

    ERIC Educational Resources Information Center

    Marchant, David C.; Greig, Matt; Bullough, Jonathan; Hitchen, Daniel

    2011-01-01

    The influence of internal (movement focus) and external (outcome focus) attentional-focusing instructions on muscular endurance were investigated using three exercise protocols with experienced exercisers. Twenty-three participants completed a maximal repetition, assisted bench-press test on a Smith's machine. An external focus of attention…

  4. Gene therapy for duchenne muscular dystrophy: expectations and challenges.

    PubMed

    Rodino-Klapac, Louise R; Chicoine, Louis G; Kaspar, Brian K; Mendell, Jerry R

    2007-09-01

    Duchenne muscular dystrophy is a debilitating X-linked disease with limited treatment options. We examined the possibility of moving forward with gene therapy, an approach that demonstrates promise for treating Duchenne muscular dystrophy. Gene therapy is not limited to replacement of defective genes but also includes strategies using surrogate genes with alternative but effective means of improving cellular function or repairing gene mutations. The first viral-mediated gene transfer for any muscle disease was carried out at Columbus Children's Research Institute and Ohio State University for limb girdle muscular dystrophy type 2D, and the first viral-mediated trial of gene transfer for Duchenne muscular dystrophy is under way at the same institutions. These studies, consisting of intramuscular injection of virus into a single muscle, are limited in scope and represent phase 1 clinical trials with safety as the primary end point. These initial clinical studies lay the foundation for future studies, providing important information about dosing, immunogenicity, and viral serotype in humans. This article highlights the challenges and potential pitfalls as the field advances this treatment modality to clinical reality.

  5. Swallow Characteristics in Patients with Oculopharyngeal Muscular Dystrophy

    ERIC Educational Resources Information Center

    Palmer, Phyllis M.; Neel, Amy T.; Sprouls, Gwyneth; Morrison, Leslie

    2010-01-01

    Purpose: This prospective investigation evaluates oral weakness and its impact on swallow function, weight, and quality of life in patients with oculopharyngeal muscular dystrophy (OPMD). Method: Intraoral pressure, swallow pressure, and endurance were measured using an Iowa Oral Performance Instrument in participants with OPMD and matched…

  6. Local muscular fatigue and attentional processes in a fencing task.

    PubMed

    Devienne, M F; Audiffren, M; Ripoll, H; Stein, J F

    2000-02-01

    Study of the effects of brief exercise on mental processes by Tomporowski and Ellis (1986) has shown that moderate muscular tension improves cognitive performance while low or high tension does not. Improvements in performance induced by exercise are commonly associated with increase in arousal, while impairments are generally attributed to the effects of muscular or central fatigue. To test two hypotheses, that (1) submaximal muscular exercise would decrease premotor time and increase would increase the attentional and preparatory effects observed in premotor time 9 men, aged 20 to 30 years, performed an isometric test at 50% of their maximum voluntary contraction between blocks of a 3-choice reaction-time fencing task. Analysis showed (1) physical exercise did not improve postexercise premotor time, (2) muscular fatigue induced by isometric contractions did not increase motor time, (3) there was no effect of exercise on attentional and preparatory processes involved in the postexercise choice-RT task. The invalidation of hypotheses was mainly explained by disparity in directional effects across subjects and by use of an exercise that was not really fatiguing.

  7. Congenital nutritional muscular dystrophy in a beef calf.

    PubMed

    Abutarbush, Sameeh M; Radostits, Otto M

    2003-09-01

    A 13-hour-old Aberdeen-Angus was involuntarily recumbent since birth. Congenital nutritional muscular dystrophy was suspected based on clinical findings, increased serum creatine kinase, and decreased serum vitamin E and selenium levels. Recovery followed after supportive therapy and parenteral vitamin E and selenium. Reports of this disease in newborn calves are unusual.

  8. Muscle Weakness and Speech in Oculopharyngeal Muscular Dystrophy

    ERIC Educational Resources Information Center

    Neel, Amy T.; Palmer, Phyllis M.; Sprouls, Gwyneth; Morrison, Leslie

    2015-01-01

    Purpose: We documented speech and voice characteristics associated with oculopharyngeal muscular dystrophy (OPMD). Although it is a rare disease, OPMD offers the opportunity to study the impact of myopathic weakness on speech production in the absence of neurologic deficits in a relatively homogeneous group of speakers. Methods: Twelve individuals…

  9. Phonological Awareness Skills in Young Boys with Duchenne Muscular Dystrophy

    ERIC Educational Resources Information Center

    Waring, Phoebe; Woodyatt, Gail

    2011-01-01

    Substantial research has detailed the reading deficits experienced by children with Duchenne muscular dystrophy (DMD). Although phonological awareness (PA) is vital in reading development, little is known about PA in the DMD population. This pilot study describes the PA abilities of a group of five young children with DMD, comparing the results…

  10. Occupational Potential in a Population with Duchenne Muscular Dystrophy.

    ERIC Educational Resources Information Center

    Schkade, Janette K.; And Others

    1987-01-01

    Twenty-five males with Duchenne muscular dystrophy were tested to assess their potential for occupational activity. Tests measured possible sensory deficits, strength, endurance, and fatigue in response to sustained fine motor activity. Results indicate that, within limitations, persons with this diagnosis can engage in activity leading to skill…

  11. The Assessment of Intelligence in Boys with Duchenne Muscular Dystrophy.

    ERIC Educational Resources Information Center

    Mearig, Judith S.

    1979-01-01

    Challenges assumptions and research procedures leading to the position that below-average intellectual potential is an integral part of Duchenne muscular dystrophy. A study of 58 boys (ages 5 to 18) from urban, suburban, and rural settings indicated IQ range of 59 to 131 and no evidence of significant verbal deficit (reported in earlier studies).…

  12. Dasatinib as a treatment for Duchenne muscular dystrophy.

    PubMed

    Lipscomb, Leanne; Piggott, Robert W; Emmerson, Tracy; Winder, Steve J

    2016-01-15

    Identification of a systemically acting and universal small molecule therapy for Duchenne muscular dystrophy would be an enormous advance for this condition. Based on evidence gained from studies on mouse genetic models, we have identified tyrosine phosphorylation and degradation of β-dystroglycan as a key event in the aetiology of Duchenne muscular dystrophy. Thus, preventing tyrosine phosphorylation and degradation of β-dystroglycan presents itself as a potential therapeutic strategy. Using the dystrophic sapje zebrafish, we have investigated the use of tyrosine kinase and other inhibitors to treat the dystrophic symptoms in this model of Duchenne muscular dystrophy. Dasatinib, a potent and specific Src tyrosine kinase inhibitor, was found to decrease the levels of β-dystroglycan phosphorylation on tyrosine and to increase the relative levels of non-phosphorylated β-dystroglycan in sapje zebrafish. Furthermore, dasatinib treatment resulted in the improved physical appearance of the sapje zebrafish musculature and increased swimming ability as measured by both duration and distance of swimming of dasatinib-treated fish compared with control animals. These data suggest great promise for pharmacological agents that prevent the phosphorylation of β-dystroglycan on tyrosine and subsequent steps in the degradation pathway as therapeutic targets for the treatment of Duchenne muscular dystrophy.

  13. Poor Facial Affect Recognition among Boys with Duchenne Muscular Dystrophy

    ERIC Educational Resources Information Center

    Hinton, V. J.; Fee, R. J.; De Vivo, D. C.; Goldstein, E.

    2007-01-01

    Children with Duchenne or Becker muscular dystrophy (MD) have delayed language and poor social skills and some meet criteria for Pervasive Developmental Disorder, yet they are identified by molecular, rather than behavioral, characteristics. To determine whether comprehension of facial affect is compromised in boys with MD, children were given a…

  14. The Child with Muscular Dystrophy in School. Revised.

    ERIC Educational Resources Information Center

    Schock, Nancy C.

    Practical information on children with muscular dystrophy is intended to help parents and teachers facilitate their inclusion in mainstreamed classrooms. Major topics addressed include the following: transportation arrangements; providing full information to the teacher regarding the child's specific abilities and physical limitations;…

  15. Phosphorylation of intact erythrocytes in human muscular dystrophy

    SciTech Connect

    Johnson, R.M.; Nigro, M.

    1986-04-01

    The uptake of exogenous /sup 32/Pi into the membrane proteins of intact erythrocytes was measured in 8 patients with Duchenne muscular dystrophy. No abnormalities were noted after autoradiographic analysis. This contrasts with earlier results obtained when isolated membranes were phosphorylated with gamma-(/sup 32/P)ATP, and suggests a possible reinterpretation of those experiments.

  16. Muscular Dystrophies at Different Ages: Metabolic and Endocrine Alterations

    PubMed Central

    Cruz Guzmán, Oriana del Rocío; Chávez García, Ana Laura; Rodríguez-Cruz, Maricela

    2012-01-01

    Common metabolic and endocrine alterations exist across a wide range of muscular dystrophies. Skeletal muscle plays an important role in glucose metabolism and is a major participant in different signaling pathways. Therefore, its damage may lead to different metabolic disruptions. Two of the most important metabolic alterations in muscular dystrophies may be insulin resistance and obesity. However, only insulin resistance has been demonstrated in myotonic dystrophy. In addition, endocrine disturbances such as hypogonadism, low levels of testosterone, and growth hormone have been reported. This eventually will result in consequences such as growth failure and delayed puberty in the case of childhood dystrophies. Other consequences may be reduced male fertility, reduced spermatogenesis, and oligospermia, both in childhood as well as in adult muscular dystrophies. These facts all suggest that there is a need for better comprehension of metabolic and endocrine implications for muscular dystrophies with the purpose of developing improved clinical treatments and/or improvements in the quality of life of patients with dystrophy. Therefore, the aim of this paper is to describe the current knowledge about of metabolic and endocrine alterations in diverse types of dystrophinopathies, which will be divided into two groups: childhood and adult dystrophies which have different age of onset. PMID:22701119

  17. Modifying muscular dystrophy through transforming growth factor-β.

    PubMed

    Ceco, Ermelinda; McNally, Elizabeth M

    2013-09-01

    Muscular dystrophy arises from ongoing muscle degeneration and insufficient regeneration. This imbalance leads to loss of muscle, with replacement by scar or fibrotic tissue, resulting in muscle weakness and, eventually, loss of muscle function. Human muscular dystrophy is characterized by a wide range of disease severity, even when the same genetic mutation is present. This variability implies that other factors, both genetic and environmental, modify the disease outcome. There has been an ongoing effort to define the genetic and molecular bases that influence muscular dystrophy onset and progression. Modifier genes for muscle disease have been identified through both candidate gene approaches and genome-wide surveys. Multiple lines of experimental evidence have now converged on the transforming growth factor-β (TGF-β) pathway as a modifier for muscular dystrophy. TGF-β signaling is upregulated in dystrophic muscle as a result of a destabilized plasma membrane and/or an altered extracellular matrix. Given the important biological role of the TGF-β pathway, and its role beyond muscle homeostasis, we review modifier genes that alter the TGF-β pathway and approaches to modulate TGF-β activity to ameliorate muscle disease.

  18. Advances in genetic therapeutic strategies for Duchenne muscular dystrophy

    PubMed Central

    Guiraud, Simon; Chen, Huijia; Burns, David T.

    2015-01-01

    New Findings What is the topic of this review? This review highlights recent progress in genetically based therapies targeting the primary defect of Duchenne muscular dystrophy. What advances does it highlight? Over the last two decades, considerable progress has been made in understanding the mechanisms underlying Duchenne muscular dystrophy, leading to the development of genetic therapies. These include manipulation of the expression of the gene or related genes, the splicing of the gene and its translation, and replacement of the gene using viral approaches. Duchenne muscular dystrophy is a lethal X‐linked disorder caused by mutations in the dystrophin gene. In the absence of the dystrophin protein, the link between the cytoskeleton and extracellular matrix is destroyed, and this severely compromises the strength, flexibility and stability of muscle fibres. The devastating consequence is progressive muscle wasting and premature death in Duchenne muscular dystrophy patients. There is currently no cure, and despite exhaustive palliative care, patients are restricted to a wheelchair by the age of 12 years and usually succumb to cardiac or respiratory complications in their late 20s. This review provides an update on the current genetically based therapies and clinical trials that target or compensate for the primary defect of this disease. These include dystrophin gene‐replacement strategies, genetic modification techniques to restore dystrophin expression, and modulation of the dystrophin homologue, utrophin, as a surrogate to re‐establish muscle function. PMID:26140505

  19. Therapeutic Potential of Immunoproteasome Inhibition in Duchenne Muscular Dystrophy.

    PubMed

    Farini, Andrea; Sitzia, Clementina; Cassani, Barbara; Cassinelli, Letizia; Rigoni, Rosita; Colleoni, Federica; Fusco, Nicola; Gatti, Stefano; Bella, Pamela; Villa, Chiara; Napolitano, Filomena; Maiavacca, Rita; Bosari, Silvano; Villa, Anna; Torrente, Yvan

    2016-11-01

    Duchenne muscular dystrophy is an inherited fatal genetic disease characterized by mutations in dystrophin gene, causing membrane fragility leading to myofiber necrosis and inflammatory cell recruitment in dystrophic muscles. The resulting environment enriched in proinflammatory cytokines, like IFN-γ and TNF-α, determines the transformation of myofiber constitutive proteasome into the immunoproteasome, a multisubunit complex involved in the activation of cell-mediate immunity. This event has a fundamental role in producing peptides for antigen presentation by MHC class I, for the immune response and also for cytokine production and T-cell differentiation. Here, we characterized for the first time the presence of T-lymphocytes activated against revertant dystrophin epitopes, in the animal model of Duchenne muscular dystrophy, the mdx mice. Moreover, we specifically blocked i-proteasome subunit LMP7, which was up-regulated in dystrophic skeletal muscles, and we demonstrated the rescue of the dystrophin expression and the amelioration of the dystrophic phenotype. The i-proteasome blocking lowered myofiber MHC class I expression and self-antigen presentation to T cells, thus reducing the specific antidystrophin T cell response, the muscular cell infiltrate, and proinflammatory cytokine production, together with muscle force recovery. We suggest that i-proteasome inhibition should be considered as new promising therapeutic approach for Duchenne muscular dystrophy pathology.

  20. The role of stem cells in muscular dystrophies.

    PubMed

    Meregalli, Mirella; Farini, Andrea; Colleoni, Federica; Cassinelli, Letizia; Torrente, Yvan

    2012-06-01

    Muscular dystrophies are heterogeneous neuromuscular disorders of inherited origin, including Duchenne muscular dystrophy (DMD). Cell-based therapies were used to promote muscle regeneration with the hope that the host cells repopulated the muscle and improved muscle function and pathology. Stem cells were preferable for therapeutic applications, due to their capacity of self-renewal and differentiative potential. In the last years, encouraging results were obtained with adult stem cells to treat muscular dystrophies. Adult stem cells were found into various tissues of the body and they were able to maintain, generate, and replace terminally differentiated cells within their own specific tissue because of cell turnover or tissue injury. Moreover, it became clear that these cells could participate into regeneration of more than just their resident organ. Here, we described multiple types of muscle and non muscle-derived myogenic stem cells, their characterization and their possible use to treat muscular dystrophies. We also underlined that most promising possibility for the management and therapy of DMD is a combination of different approaches, such as gene and stem cell therapy.

  1. Deformable mirror designs for extreme AO (XAO)

    NASA Astrophysics Data System (ADS)

    Cavaco, Jeffrey; Wirth, Allan

    2014-08-01

    One of the science missions for the next generation of extremely large ground based telescopes (30-42m apertures) is the imaging and spectroscopy of exoplanets. To achieve that goal an Adaptive Optics (AO) subsystem with a very large number of corrected modes is required. To provide contrast ratios in the range of 10-9 or better for a 42m telescope an AO system with 25,000 to 60,000 channels will be needed. This is approximately an order of magnitude beyond the current state of the art. Adaptive Optics Associates Xinetics has developed the Photonex Module Deformable Mirror (DM) technology specifically to address the needs of extreme AO for high contrast applications. A Photonex Module is a monolithic block of electrostrictive ceramic in which a high density of individually addressable actuators are formed by screen printing of electrodes and partial wire saw cutting of the ceramic. The printed electrode structures also allow all electrical connections to be made at the back surface of the module via flex circuits. Actuator spacings of 1mm or less have been achieved using this approach. The individual modules can be edge butted and bonded to achieve high actuator count. The largest DMs fabricated to date have 4096 actuators in a 64X64mm array. In this paper the engineering challenges in extending this technology by a factor of ten or more in actuator count will be discussed. A conceptual design for a DM suitable for XAO will be presented. Approaches for a support structure that will maintain the low spatial frequency surface figure of this large (~0.6m) DM and for the electrical interface to the tens of thousands of actuators will be discussed. Finally, performance estimates will be presented.

  2. AO corrected satellite imaging from Mount Stromlo

    NASA Astrophysics Data System (ADS)

    Bennet, F.; Rigaut, F.; Price, I.; Herrald, N.; Ritchie, I.; Smith, C.

    2016-07-01

    The Research School of Astronomy and Astrophysics have been developing adaptive optics systems for space situational awareness. As part of this program we have developed satellite imaging using compact adaptive optics systems for small (1-2 m) telescopes such as those operated by Electro Optic Systems (EOS) from the Mount Stromlo Observatory. We have focused on making compact, simple, and high performance AO systems using modern high stroke high speed deformable mirrors and EMCCD cameras. We are able to track satellites down to magnitude 10 with a Strehl in excess of 20% in median seeing.

  3. Targeting mRNA for the treatment of facioscapulohumeral muscular dystrophy

    PubMed Central

    Bao, Bo; Maruyama, Rika; Yokota, Toshifumi

    2016-01-01

    Summary Facioscapulohumeral muscular dystrophy (FSHD) is an inherited autosomal dominant disorder characterized clinically by progressive muscle degeneration. Currently, no curative treatment for this disorder exists. FSHD patients are managed through physiotherapy to improve function and quality of life. Over the last two decades, FSHD has been better understood as a disease genetically characterized by a pathogenic contraction of a subset of macrosatellite repeats on chromosome 4. Specifically, several studies support an FSHD pathogenesis model involving the aberrant expression of the double homeobox protein 4 (DUX4) gene. Hence, potential therapies revolving around inhibition of DUX4 have been explored. One of the potential treatment options is the use of effective antisense oligonucleotides (AOs) to knockdown expression of the myopathic DUX4 gene and its downstream molecules including paired-like homeodomain transcription factor 1 (PITX1). Success in the suppression of PITX1 expression has already been demonstrated systemically in vivo in recent studies. In this article, we will review the pathogenesis of FSHD and the latest research involving the use of antisense knockdown therapy. PMID:27672539

  4. Microdystrophin Ameliorates Muscular Dystrophy in the Canine Model of Duchenne Muscular Dystrophy

    PubMed Central

    Shin, Jin-Hong; Pan, Xiufang; Hakim, Chady H; Yang, Hsiao T; Yue, Yongping; Zhang, Keqing; Terjung, Ronald L; Duan, Dongsheng

    2013-01-01

    Dystrophin deficiency results in lethal Duchenne muscular dystrophy (DMD). Substituting missing dystrophin with abbreviated microdystrophin has dramatically alleviated disease in mouse DMD models. Unfortunately, translation of microdystrophin therapy has been unsuccessful in dystrophic dogs, the only large mammalian model. Approximately 70% of the dystrophin-coding sequence is removed in microdystrophin. Intriguingly, loss of ≥50% dystrophin frequently results in severe disease in patients. To test whether the small gene size constitutes a fundamental design error for large mammalian muscle, we performed a comprehensive study using 22 dogs (8 normal and 14 dystrophic). We delivered the ΔR2-15/ΔR18-19/ΔR20-23/ΔC microdystrophin gene to eight extensor carpi ulnaris (ECU) muscles in six dystrophic dogs using Y713F tyrosine mutant adeno-associated virus (AAV)-9 (2.6 × 1013 viral genome (vg) particles/muscle). Robust expression was observed 2 months later despite T-cell infiltration. Major components of the dystrophin-associated glycoprotein complex (DGC) were restored by microdystrophin. Treated muscle showed less inflammation, fibrosis, and calcification. Importantly, therapy significantly preserved muscle force under the stress of repeated cycles of eccentric contraction. Our results have established the proof-of-concept for microdystrophin therapy in dystrophic muscles of large mammals and set the stage for clinical trial in human patients. PMID:23319056

  5. Microdystrophin ameliorates muscular dystrophy in the canine model of duchenne muscular dystrophy.

    PubMed

    Shin, Jin-Hong; Pan, Xiufang; Hakim, Chady H; Yang, Hsiao T; Yue, Yongping; Zhang, Keqing; Terjung, Ronald L; Duan, Dongsheng

    2013-04-01

    Dystrophin deficiency results in lethal Duchenne muscular dystrophy (DMD). Substituting missing dystrophin with abbreviated microdystrophin has dramatically alleviated disease in mouse DMD models. Unfortunately, translation of microdystrophin therapy has been unsuccessful in dystrophic dogs, the only large mammalian model. Approximately 70% of the dystrophin-coding sequence is removed in microdystrophin. Intriguingly, loss of ≥50% dystrophin frequently results in severe disease in patients. To test whether the small gene size constitutes a fundamental design error for large mammalian muscle, we performed a comprehensive study using 22 dogs (8 normal and 14 dystrophic). We delivered the ΔR2-15/ΔR18-19/ΔR20-23/ΔC microdystrophin gene to eight extensor carpi ulnaris (ECU) muscles in six dystrophic dogs using Y713F tyrosine mutant adeno-associated virus (AAV)-9 (2.6 × 10(13) viral genome (vg) particles/muscle). Robust expression was observed 2 months later despite T-cell infiltration. Major components of the dystrophin-associated glycoprotein complex (DGC) were restored by microdystrophin. Treated muscle showed less inflammation, fibrosis, and calcification. Importantly, therapy significantly preserved muscle force under the stress of repeated cycles of eccentric contraction. Our results have established the proof-of-concept for microdystrophin therapy in dystrophic muscles of large mammals and set the stage for clinical trial in human patients.

  6. Evaluation of muscular lesions in connective tissue diseases: thallium 201 muscular scans

    SciTech Connect

    Guillet, G.; Guillet, J.; Sanciaume, C.; Maleville, J.; Geniaux, M.; Morin, P.

    1988-04-01

    We performed thallium 201 muscle scans to assess muscular involvement in 40 patients with different connective tissue diseases (7 with dermatomyositis, 7 with systemic lupus erythematosus, 12 with progressive systemic scleroderma, 2 with calcinosis, Raynaud's phenomenon, esophageal involvement, sclerodactyly, and telangiectasia (CREST) syndrome, 3 with monomelic scleroderma, 6 with morphea, and 3 with Raynaud's disease). Only 12 of these patients complained of fatigability and/or myalgia. Electromyography was performed and serum levels of muscle enzymes were measured in all patients. Comparison of thallium 201 exercise recording with the other tests revealed that scan sensitivity is greater than electromyographic and serum muscle enzymes levels. Thallium 201 scans showed abnormal findings in 32 patients and revealed subclinical lesions in 18 patients, while electromyography findings were abnormal in 25 of these 32 patients. Serum enzyme levels were raised in only 8 patients. Thallium 201 scanning proved to be a useful guide for modifying therapy when laboratory data were conflicting. It was useful to evaluate treatment efficacy. Because our data indicate a 100% positive predictive value, we believe that thallium 201 scanning should be advised for severe systemic connective tissue diseases with discordant test results.

  7. AO Observations of Three Powerful Radio Galaxies

    SciTech Connect

    de Vries, W; van Bruegel, W; Quirrenbach, A

    2002-08-01

    The host galaxies of powerful radio sources are ideal laboratories to study active galactic nuclei (AGN). The galaxies themselves are among the most massive systems in the universe, and are believed to harbor supermassive black holes (SMBH). If large galaxies are formed in a hierarchical way by multiple merger events, radio galaxies at low redshift represent the end-products of this process. However, it is not clear why some of these massive ellipticals have associated radio emission, while others do not. Both are thought to contain SMBHs, with masses proportional to the total luminous mass in the bulge. It either implies every SMBH has recurrent radio-loud phases, and the radio-quiet galaxies happen to be in the ''low'' state, or that the radio galaxy nuclei are physically different from radio-quiet ones, i.e. by having a more massive SMBH for a given bulge mass. Here we present the first results from our adaptive optics imaging and spectroscopy pilot program on three nearby powerful radio galaxies. Initiating a larger, more systematic AO survey of radio galaxies (preferentially with Laser Guide Star equipped AO systems) has the potential of furthering our understanding of the physical properties of radio sources, their triggering, and their subsequent evolution.

  8. A Prospective Investigation of Interpersonal Influences on the Pursuit of Muscularity in Late Adolescent Boys and Girls

    PubMed Central

    Shomaker, Lauren B.; Furman, Wyndol

    2010-01-01

    This project examined whether interpersonal pressure to be muscular predicted late adolescents’ pursuit of muscularity. Participants were 199 adolescents (16–19 years), mothers (n=175), and friends (n=159), assessed at two annual times. Pressure to be muscular was assessed with adolescents’, mothers’, and friends’ reports of their relationships. Adolescents reported pressure from fathers and romantic partners, appearance satisfaction, disordered eating, and pursuit of muscularity. Adolescents,’ mothers’, and friends’ reports of pressure related to pursuit of muscularity at both times. Adolescents’ perceptions and mothers’ reports prospectively predicted pursuit of muscularity. Findings highlight the relevance of relationships to pursuit of muscularity in late adolescents. PMID:20348360

  9. Muscular activity may improve in edentulous patients after implant treatment.

    PubMed

    Afrashtehfar, Kelvin I; Schimmel, Martin

    2016-12-01

    Data sourcesMedline via Pubmed and the Cochrane Library were searched from January 1980 to September 2013. This was complemented by a manual search of the magazines Deutsche Zahnaerztliche Zeitung, Quintessenz, Zeitschrift für Zahnärztliche Implantologie, Schweizerische Monatszeitschrift and Implantologie. Additionally, the list of reference s of all selected full-text articles and related reviews were further scrutinised for potential included studies in English or German.Study selectionThree review authors independently searched for clinical trials that assessed the muscular activity in the intervention groups: edentulous patients treated with implant-overdentures (IODs) and implant-supported fixed dental prostheses (ISFDPs) and the comparison groups: dentates and edentulous patients treated with mucosa-borne complete removable dental prostheses (CRDPs).Data extraction and synthesisThe primary outcome was the muscular activity (measured by electromyography [EMG]) in masseter or temporalis muscle of the participants during clenching and chewing. The data extraction of each included study consisted of author, year, age range, treatment, number of participants, number of implants inserted, arch treated, opposite jaw, kind and side of the muscles that were measured. EMG gain or loss (unit measured: volt) was considered by using the effect size. For the meta-analyses only the studies that included masseter muscle measured separately from temporalis were considered. Concerning the side of measurement (right and left side measured together or right and left side measured separately), only the dominant type in each category was included.ResultsSixteen articles, out of the initial 646 retrieved abstracts, were analysed. The muscular activity of edentulous subjects increased after implant support therapy during clenching (effect size [ES]: 2.18 [95% confidence interval [CI]: 1.14, 3.23]) and during chewing (ES: 1.45 [95 % CI: 1.21, 1.69]). In addition, the pooled EMG

  10. Diferentes Metodologias Aplicadas ao Ensino de Astronomia

    NASA Astrophysics Data System (ADS)

    Albrecht, E.; Voelzke, M. R.

    2007-08-01

    Espera-se que o educando ao final da educação básica, adquira uma compreensão atualizada das hipóteses, modelos e formas de investigação sobre a origem e evolução do Universo em que vive. O presente trabalho tem como principal objetivo compreender dentre três práticas pedagógicas adotadas no Ensino de Astronomia, na terceira série do Ensino Médio, da Escola Estadual Colônia dos Pescadores, qual melhor cumpre o papel de formação e aprendizagem para vida. A pesquisa preliminar foi através de um questionário onde o intuito foi diagnosticar o conhecimento já existente acerca do tema em questão. O questionário é composto de vinte questões dissertativas e objetivas, onde os educandos das três turmas envolvidas o responderam. Este trabalho utiliza as seguintes metodologias: a tradicional, onde o professor é um repassador de informações, fazendo uso exclusivo de lousa e giz; a segunda também de forma tradicional, porém com auxílio de multimídia para desenvolvimento das aulas e aterceira sob forma de seminários, elaborados e apresentados pelos educandos, no qual o educador faz apenas as intervenções necessárias. Ao final do trabalho os alunos responderão novamente o questionário inicial para diagnosticar dentre as três metodologias utilizadas qual apresentou melhor resultado. Os resultados preliminares obtidos, já podem ser observados e, dos 119 alunos entrevistados, as respostas obtidas são as mais diversas e evidenciam que a grande maioria nunca teve em sua vida escolar o tema Astronomia. Ao serem questionados se já haviam estudado Astronomia as respostas foram: turma A: sim 43%; turma B: sim: 21%; turma C: sim: 24%. Porém quando questionados a respeito do significado de Astronomia observou-se que: turma A: 100% de acertos; turma B: 64% acertos; turma C: 84% de acertos, demonstrando claramente a aprendizagem em diferentes esferas, não dependendo unicamente da escola. Até o presente momento, verificou-se que há interesse em

  11. AO Infrared Imaging of M71 Core

    NASA Astrophysics Data System (ADS)

    Ruberg, Andres; Richer, H.; Brewer, J.; Davis, S.; Hickson, P.; Knigge, C.; Dieball, A.; Hurley, J.; Shara, M.; Hansen, B.; Gebhardt, K.; Fahlman, G.

    2007-05-01

    In this poster we present infrared H and K AO data taken with ALTAIR/NIRI on Gemini North of the globular cluster Messier 71. This data represents approximately 22ks of observations in H and 17ks in K, in a field 22x22 arcsec centered on the core of the cluster. These data were secured under superb conditions and will provide an excellent opportunity to pursue our scientific goals. These goals include the observation of the end of hydrogen-burning main sequence in a moderately metal-rich globular cluster and, by fitting the brightness profile and looking for deviations from a King model, we will search for evidence for a central black hole in this cluster.

  12. Mechanisms and assessment of statin-related muscular adverse effects.

    PubMed

    Moßhammer, Dirk; Schaeffeler, Elke; Schwab, Matthias; Mörike, Klaus

    2014-09-01

    Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers.

  13. Biomechanical analysis of the muscular power of martial arts athletes.

    PubMed

    Machado, S M; Osório, R A L; Silva, N S; Magini, M

    2010-06-01

    This study analyzes the performance of knee extension and flexion of Taekwondo and Kickboxing athletes. The power values were extracted through electromyography obtained by an isokinetic dynamometer at 60 degrees per second. These values are resulted from the square of the electromyography signal. The analysis of kick power was made using a modified wavelet algorithm considering values with 95% significance. Both groups presented equivalent power and torque capacity with different training times and experience, on the other hand, the wavelet analysis showed better results in muscular recruitment performance in athletes with more experience, in other words, power is not only performance but also power plus recruitment produces better results. This study uniquely showed that muscular enhancement capacity is not only related to the power capacity of contraction but also to motor coordination.

  14. Muscular dystrophy meets protein biochemistry, the mother of invention.

    PubMed

    Funk, Steven D; Miner, Jeffrey H

    2017-03-01

    Muscular dystrophies result from a defect in the linkage between the muscle fiber cytoskeleton and the basement membrane (BM). Congenital muscular dystrophy type MDC1A is caused by mutations in laminin α2 that either reduce its expression or impair its ability to polymerize within the muscle fiber BM. Defects in this BM lead to muscle fiber damage from the force of contraction. In this issue of the JCI, McKee and colleagues use a laminin polymerization-competent, designer chimeric BM protein in vivo to restore function of a polymerization-defective laminin, leading to normalized muscle structure and strength in a mouse model of MDC1A. Delivery of such a protein to patients could ameliorate many aspects of their disease.

  15. Fibrogenic Cell Plasticity Blunts Tissue Regeneration and Aggravates Muscular Dystrophy.

    PubMed

    Pessina, Patrizia; Kharraz, Yacine; Jardí, Mercè; Fukada, So-ichiro; Serrano, Antonio L; Perdiguero, Eusebio; Muñoz-Cánoves, Pura

    2015-06-09

    Preservation of cell identity is necessary for homeostasis of most adult tissues. This process is challenged every time a tissue undergoes regeneration after stress or injury. In the lethal Duchenne muscular dystrophy (DMD), skeletal muscle regenerative capacity declines gradually as fibrosis increases. Using genetically engineered tracing mice, we demonstrate that, in dystrophic muscle, specialized cells of muscular, endothelial, and hematopoietic origins gain plasticity toward a fibrogenic fate via a TGFβ-mediated pathway. This results in loss of cellular identity and normal function, with deleterious consequences for regeneration. Furthermore, this fibrogenic process involves acquisition of a mesenchymal progenitor multipotent status, illustrating a link between fibrogenesis and gain of progenitor cell functions. As this plasticity also was observed in DMD patients, we propose that mesenchymal transitions impair regeneration and worsen diseases with a fibrotic component.

  16. The importance of genetic diagnosis for Duchenne muscular dystrophy

    PubMed Central

    Aartsma-Rus, Annemieke; Ginjaar, Ieke B; Bushby, Kate

    2016-01-01

    Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy are caused by mutations in the dystrophin-encoding DMD gene. Large deletions and duplications are most common, but small mutations have been found as well. Having a correct diagnosis is important for family planning and providing proper care to patients according to published guidelines. With mutation-specific therapies under development for DMD, a correct diagnosis is now also important for assessing whether patients are eligible for treatments. This review discusses different mutations causing DMD, diagnostic techniques available for making a genetic diagnosis for children suspected of DMD and the importance of having a specific genetic diagnosis in the context of emerging genetic therapies for DMD. PMID:26754139

  17. Satellite Cells in Muscular Dystrophy - Lost in Polarity.

    PubMed

    Chang, Natasha C; Chevalier, Fabien P; Rudnicki, Michael A

    2016-06-01

    Recent findings employing the mdx mouse model for Duchenne muscular dystrophy (DMD) have revealed that muscle satellite stem cells play a direct role in contributing to disease etiology and progression of DMD, the most common and severe form of muscular dystrophy. Lack of dystrophin expression in DMD has critical consequences in satellite cells including an inability to establish cell polarity, abrogation of asymmetric satellite stem-cell divisions, and failure to enter the myogenic program. Thus, muscle wasting in dystrophic mice is not only caused by myofiber fragility but is exacerbated by intrinsic satellite cell dysfunction leading to impaired regeneration. Despite intense research and clinical efforts, there is still no effective cure for DMD. In this review we highlight recent research advances in DMD and discuss the current state of treatment and, importantly, how we can incorporate satellite cell-targeted therapeutic strategies to correct satellite cell dysfunction in DMD.

  18. Mindfulness, body image, and drive for muscularity in men.

    PubMed

    Lavender, Jason M; Gratz, Kim L; Anderson, Drew A

    2012-03-01

    Studies have shown that dispositional mindfulness, a construct characterized by awareness and attention to present moment experiences, is associated with body image constructs in women. However, little is known about the relationship between dispositional mindfulness and body image among men. Therefore, this study examined the unique associations between dispositional mindfulness and three body image variables in men: overall appearance evaluation, satisfaction with distinct body areas, and drive for muscularity. Undergraduate men (N=296) completed the Multidimensional Body Self-Relations Questionnaire-Appearance Scales, the Drive for Muscularity Scale, the Mindful Attention Awareness Scale, and the Positive and Negative Affect Schedule. A series of hierarchical regression analyses revealed that mindfulness was uniquely associated with all three body image variables after accounting for body mass index and negative affect. Results are discussed with regard to the potential role of dispositional mindfulness in body dissatisfaction among men.

  19. Spinal muscular atrophy: development and implementation of potential treatments.

    PubMed

    Arnold, W David; Burghes, Arthur H M

    2013-09-01

    In neurodegenerative disorders, effective treatments are urgently needed, along with methods to determine whether treatment worked. In this review, we discuss the rapid progress in the understanding of recessive proximal spinal muscular atrophy and how this is leading to exciting potential treatments of the disease. Spinal muscular atrophy is caused by loss of the survival motor neuron 1 (SMN1) gene and reduced levels of SMN protein. The critical downstream targets of SMN deficiency that result in motor neuron loss are not known. However, increasing SMN levels has a marked impact in mouse models, and these therapeutics are rapidly moving toward clinical trials. Promising preclinical therapies, the varying degree of impact on the mouse models, and potential measures of treatment effect are reviewed. One key issue discussed is the variable outcome of increasing SMN at different stages of disease progression.

  20. Eyeball pseudo-muscular actuators for an android face

    NASA Astrophysics Data System (ADS)

    Carpi, Federico; De Rossi, Danilo

    2005-05-01

    The human attention system is based on the capability of the eye of focusing and tracking. These actions are performed by the eyeball muscle system, as a consequence of visual stimuli. The F.A.C.E. (Facial Automaton for Conveying Emotions) project at our lab concerns the development of an android face endowed with dynamic expressiveness and artificial vision. Aimed at realising an artificial attention system for such an automaton, we present here a study for the development of pseudo-muscular polymer actuators for its eyeballs. The system is based on the mimicry of the muscular architecture of the human eye. In particular, linear actuators made of dielectric elastomers have been designed to replicate actions exerted by the main ocular muscles.

  1. Gene Therapy for Muscular Dystrophies: Progress and Challenges

    PubMed Central

    Oh, Donghoon

    2010-01-01

    Muscular dystrophies are groups of inherited progressive diseases of the muscle caused by mutations of diverse genes related to normal muscle function. Although there is no current effective treatment for these devastating diseases, various molecular strategies have been developed to restore the expressions of the associated defective proteins. In preclinical animal models, both viral and nonviral vectors have been shown to deliver recombinant versions of defective genes. Antisense oligonucleotides have been shown to modify the splicing mechanism of mesenger ribonucleic acid to produce an internally deleted but partially functional dystrophin in an experimental model of Duchenne muscular dystrophy. In addition, chemicals can induce readthrough of the premature stop codon in nonsense mutations of the dystrophin gene. On the basis of these preclinical data, several experimental clinical trials are underway that aim to demonstrate efficacy in treating these devastating diseases. PMID:20944811

  2. Halofuginone promotes satellite cell activation and survival in muscular dystrophies.

    PubMed

    Barzilai-Tutsch, Hila; Bodanovsky, Anna; Maimon, Hadar; Pines, Mark; Halevy, Orna

    2016-01-01

    Halofuginone is a leading agent in preventing fibrosis and inflammation in various muscular dystrophies. We hypothesized that in addition to these actions, halofuginone directly promotes the cell-cycle events of satellite cells in the mdx and dysf(-/-) mouse models of early-onset Duchenne muscular dystrophy and late-onset dysferlinopathy, respectively. In both models, addition of halofuginone to freshly prepared single gastrocnemius myofibers derived from 6-week-old mice increased BrdU incorporation at as early as 18h of incubation, as well as phospho-histone H3 (PHH3) and MyoD protein expression in the attached satellite cells, while having no apparent effect on myofibers derived from wild-type mice. BrdU incorporation was abolished by an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated protein kinase, suggesting involvement of this pathway in mediating halofuginone's effects on cell-cycle events. In cultures of myofibers and myoblasts isolated from dysf(-/-) mice, halofuginone reduced Bax and induced Bcl2 expression levels and induced Akt phosphorylation in a time-dependent manner. Addition of an inhibitor of the phosphinositide-3-kinase/Akt pathway reversed the halofuginone-induced cell survival, suggesting this pathway's involvement in mediating halofuginone's effects on survival. Thus, in addition to its known role in inhibiting fibrosis and inflammation, halofuginone plays a direct role in satellite cell activity and survival in muscular dystrophies, regardless of the mutation. These actions are of the utmost importance for improving muscle pathology and function in muscular dystrophies.

  3. Gene therapy for muscular dystrophy: lessons learned and path forward.

    PubMed

    Mendell, Jerry R; Rodino-Klapac, Louise; Sahenk, Zarife; Malik, Vinod; Kaspar, Brian K; Walker, Christopher M; Clark, K Reed

    2012-10-11

    Our Translational Gene Therapy Center has used small molecules for exon skipping and mutation suppression and gene transfer to replace or provide surrogate genes as tools for molecular-based approaches for the treatment of muscular dystrophies. Exon skipping is targeted at the pre-mRNA level allowing one or more exons to be omitted to restore the reading frame. In Duchenne Muscular Dystrophy (DMD), clinical trials have been performed with two different oligomers, a 2'O-methyl-ribo-oligonucleoside-phosphorothioate (2'OMe) and a phosphorodiamidate morpholino (PMO). Both have demonstrated early evidence of efficacy. A second molecular approach involves suppression of stop codons to promote readthrough of the DMD gene. We have been able to establish proof of principle for mutation suppression using the aminoglycoside, gentamicin. A safer, orally administered, alternative agent referred to as Ataluren (PTC124) has been used in clinical trials and is currently under consideration for approval by the FDA. Using a gene therapy approach, we have completed two trials and have initiated a third. For DMD, we used a mini-dystrophin transferred in adeno-associated virus (AAV). In this trial an immune response was seen directed against transgene product, a quite unexpected outcome that will help guide further studies. For limb girdle muscular dystrophy 2D (alpha-sarcoglycan deficiency), the transgene was again transferred using AAV but in this study, a muscle specific creatine kinase promoter controlled gene expression that persisted for six months. A third gene therapy trial has been initiated with transfer of the follistatin gene in AAV directly to the quadriceps muscle. Two diseases with selective quadriceps muscle weakness are undergoing gene transfer including sporadic inclusion body myositis (sIBM) and Becker muscular dystrophy (BMD). Increasing the size and strength of the muscle is the goal of this study. Most importantly, no adverse events have been encountered in any of

  4. Muscular pattern in three species of Macrostomum (platyhelminthes, macrostomorpha).

    PubMed

    Adami, Mariana L; Brusa, Francisco; Ronderos, Jorge R; Damborenea, Cristina

    2017-02-01

    Previous studies demonstrated complex architecture of the muscular system of Macrostomum species, especially in the rostrum area and the pharynx. However, little is known about the differences in muscular pattern between species of the genus. This study examines and compares the muscular systems of specimens belonging to three freshwater Macrostomum species (M. quiritium, M. tuba and M. velastylum), labeled with phalloidin-rhodamine and studied by confocal microscopy. Our results agree with the previous descriptions, confirming that the muscular patterns for the body wall, rostrum area, pharynx and caudal region differ among species. The muscles of the body wall follow the typical architecture, but the number of fibers in the species analyzed varies between dorsal and ventral surfaces, ranging from 80 to 100 fibers, this record being higher than previous observations. The arrangement of the fibers in the rostrum is complex, especially in the brain area. Macrostomum tuba and M. quiritium have a set of two muscles crossing at brain level and forming an "X," which is not evident in M. velastylum. We identified five different sets of fibers associated to the pharynx and mouth at ventral, medium and deep levels. These different sets are present in all three species studied. The caudal plate in M. tuba has an additional layer of diagonal fibers in the body wall, which is not evident in the other two species. The muscles of the reproductive system are independent of the body wall musculature in the species analyzed, but connected to the intestinal wall by specific fibers that may serve as an anchor. J. Morphol. 278:264-282, 2017. © 2016 Wiley Periodicals,Inc.

  5. Therapy for Duchenne muscular dystrophy: renewed optimism from genetic approaches.

    PubMed

    Fairclough, Rebecca J; Wood, Matthew J; Davies, Kay E

    2013-06-01

    Duchenne muscular dystrophy (DMD) is a devastating progressive disease for which there is currently no effective treatment except palliative therapy. There are several promising genetic approaches, including viral delivery of the missing dystrophin gene, read-through of translation stop codons, exon skipping to restore the reading frame and increased expression of the compensatory utrophin gene. The lessons learned from these approaches will be applicable to many other disorders.

  6. RESPIRATORY DYSFUNCTION IN UNSEDATED DOGS WITH GOLDEN RETRIEVER MUSCULAR DYSTROPHY

    PubMed Central

    DeVanna, Justin C.; Kornegay, Joe N.; Bogan, Daniel J.; Bogan, Janet R.; Dow, Jennifer L.; Hawkins, Eleanor C.

    2013-01-01

    Golden retriever muscular dystrophy (GRMD) is a well-established model of Duchenne muscular dystrophy. The value of this model would be greatly enhanced with practical tools to monitor progression of respiratory dysfunction during treatment trials. Arterial blood gas analysis, tidal breathing spirometry, and respiratory inductance plethysmography (RIP) were performed to determine if quantifiable abnormalities could be identified in unsedated, untrained, GRMD dogs. Results from 11 dogs with a mild phenotype of GRMD and 11 age-matched carriers were compared. Arterial blood gas analysis was successfully performed in all dogs, spirometry in 21 of 22 (95%) dogs, and RIP in 18 of 20 (90%) dogs. Partial pressure of carbon dioxide and bicarbonate concentration were higher in GRMD dogs. Tidal breathing peak expiratory flows were markedly higher in GRMD dogs. Abnormal abdominal motion was present in 7 of 10 (70%) GRMD dogs. Each technique provided objective, quantifiable measures that will be useful for monitoring respiratory function in GRMD dogs during clinical trials while avoiding the influence of sedation on results. Increased expiratory flows and the pattern of abdominal breathing are novel findings, not reported in people with Duchenne muscular dystrophy, and might be a consequence of hyperinflation. PMID:24295812

  7. Muscular dystrophy in PTFR/cavin-1 null mice

    PubMed Central

    Ding, Shi-Ying; Pilch, Paul F.

    2017-01-01

    ice and humans lacking the caveolae component polymerase I transcription release factor (PTRF, also known as cavin-1) exhibit lipo- and muscular dystrophy. Here we describe the molecular features underlying the muscle phenotype for PTRF/cavin-1 null mice. These animals had a decreased ability to exercise, and exhibited muscle hypertrophy with increased muscle fiber size and muscle mass due, in part, to constitutive activation of the Akt pathway. Their muscles were fibrotic and exhibited impaired membrane integrity accompanied by an apparent compensatory activation of the dystrophin-glycoprotein complex along with elevated expression of proteins involved in muscle repair function. Ptrf deletion also caused decreased mitochondrial function, oxygen consumption, and altered myofiber composition. Thus, in addition to compromised adipocyte-related physiology, the absence of PTRF/cavin-1 in mice caused a unique form of muscular dystrophy with a phenotype similar or identical to that seen in humans lacking this protein. Further understanding of this muscular dystrophy model will provide information relevant to the human situation and guidance for potential therapies. PMID:28289716

  8. Molecular Signatures of Membrane Protein Complexes Underlying Muscular Dystrophy*

    PubMed Central

    Turk, Rolf; Hsiao, Jordy J.; Smits, Melinda M.; Ng, Brandon H.; Pospisil, Tyler C.; Jones, Kayla S.; Campbell, Kevin P.; Wright, Michael E.

    2016-01-01

    Mutations in genes encoding components of the sarcolemmal dystrophin-glycoprotein complex (DGC) are responsible for a large number of muscular dystrophies. As such, molecular dissection of the DGC is expected to both reveal pathological mechanisms, and provides a biological framework for validating new DGC components. Establishment of the molecular composition of plasma-membrane protein complexes has been hampered by a lack of suitable biochemical approaches. Here we present an analytical workflow based upon the principles of protein correlation profiling that has enabled us to model the molecular composition of the DGC in mouse skeletal muscle. We also report our analysis of protein complexes in mice harboring mutations in DGC components. Bioinformatic analyses suggested that cell-adhesion pathways were under the transcriptional control of NFκB in DGC mutant mice, which is a finding that is supported by previous studies that showed NFκB-regulated pathways underlie the pathophysiology of DGC-related muscular dystrophies. Moreover, the bioinformatic analyses suggested that inflammatory and compensatory mechanisms were activated in skeletal muscle of DGC mutant mice. Additionally, this proteomic study provides a molecular framework to refine our understanding of the DGC, identification of protein biomarkers of neuromuscular disease, and pharmacological interrogation of the DGC in adult skeletal muscle https://www.mda.org/disease/congenital-muscular-dystrophy/research. PMID:27099343

  9. Gene therapy for muscular dystrophy: current progress and future prospects.

    PubMed

    Trollet, Capucine; Athanasopoulos, Takis; Popplewell, Linda; Malerba, Alberto; Dickson, George

    2009-07-01

    Muscular dystrophies refer to a group of inherited disorders characterized by progressive muscle weakness, wasting and degeneration. So far, there is no effective treatment but new gene-based therapies are currently being developed with particular noted advances in using conventional gene replacement strategies, RNA-based approaches, or cell-based gene therapy with a main focus on Duchenne muscular dystrophy (DMD). DMD is the most common and severe form of muscular dystrophy and current treatments are far from adequate. However, genetic and cell-based therapies, in particular exon skipping induced by antisense strategies, and corrective gene therapy via functionally engineered dystrophin genes hold great promise, with several clinical trials ongoing. Proof-of-concept of exon skipping has been obtained in animal models, and most recently in clinical trials; this approach represents a promising therapy for a subset of patients. In addition, gene-delivery-based strategies exist both for antisense-induced reading frame restoration, and for highly efficient delivery of functional dystrophin mini- and micro-genes to muscle fibres in vivo and muscle stem cells ex-vivo. In particular, AAV-based vectors show efficient systemic gene delivery to skeletal muscle directly in vivo, and lentivirus-based vectors show promise of combining ex vivo gene modification strategies with cell-mediated therapies.

  10. COUP-TFII regulates satellite cell function and muscular dystrophy

    PubMed Central

    Xie, Xin; Tsai, Sophia Y.

    2016-01-01

    Duchenne muscular dystrophy (DMD) is a severe and progressive muscle-wasting disease caused by mutations in the dystrophin gene. Although dystrophin deficiency in myofiber triggers the disease’s pathological changes, the degree of satellite cell (SC) dysfunction defines disease progression. Here, we have identified chicken ovalbumin upstream promoter–transcription factor II (COUP-TFII) hyperactivity as a contributing factor underlying muscular dystrophy in a dystrophin-deficient murine model of DMD. Ectopic expression of COUP-TFII in murine SCs led to Duchenne-like dystrophy in the muscles of control animals and exacerbated degenerative myopathies in dystrophin-deficient mice. COUP-TFII–overexpressing mice exhibited regenerative failure that was attributed to deficient SC proliferation and myoblast fusion. Mechanistically, we determined that COUP-TFII coordinated a regenerative program through combined regulation of multiple promyogenic factors. Furthermore, inhibition of COUP-TFII preserved SC function and counteracted the muscle weakness associated with Duchenne-like dystrophy in the murine model, suggesting that targeting COUP-TFII is a potential treatment for DMD. Together, our findings reveal a regulatory role of COUP-TFII in the development of muscular dystrophy and open up a potential therapeutic opportunity for managing disease progression in patients with DMD. PMID:27617862

  11. Genetic Engineering of Dystroglycan in Animal Models of Muscular Dystrophy.

    PubMed

    Sciandra, Francesca; Bigotti, Maria Giulia; Giardina, Bruno; Bozzi, Manuela; Brancaccio, Andrea

    2015-01-01

    In skeletal muscle, dystroglycan (DG) is the central component of the dystrophin-glycoprotein complex (DGC), a multimeric protein complex that ensures a strong mechanical link between the extracellular matrix and the cytoskeleton. Several muscular dystrophies arise from mutations hitting most of the components of the DGC. Mutations within the DG gene (DAG1) have been recently associated with two forms of muscular dystrophy, one displaying a milder and one a more severe phenotype. This review focuses specifically on the animal (murine and others) model systems that have been developed with the aim of directly engineering DAG1 in order to study the DG function in skeletal muscle as well as in other tissues. In the last years, conditional animal models overcoming the embryonic lethality of the DG knock-out in mouse have been generated and helped clarifying the crucial role of DG in skeletal muscle, while an increasing number of studies on knock-in mice are aimed at understanding the contribution of single amino acids to the stability of DG and to the possible development of muscular dystrophy.

  12. Muscular activation patterns of the bow arm in recurve archery.

    PubMed

    Ertan, Hayri

    2009-05-01

    In archery shooting, the archer should hold the bow in place using only the pressure produced through drawing back the bowstring. Most coaches discourage the archer from gripping the bow as this is believed to produce a sideways deflecting torque on the bow and arrow during the release. The purpose of this study was to compare the bow hand forearm muscular activation patterns of elite archers with beginners to define the muscular contraction-relaxation strategies in the bow hand forearm muscles during archery shooting and investigate the effects of performance level on these strategies. Electromyographic activity of the M. flexor digitorum superficialis and the M. extensor digitorum of 10 elite and 10 beginner archers were recorded together with a pulse synchronized with the clicker snap. Raw electromyographic records as 1s before and after the clicker pulse were rectified, integrated, and normalized. The data was then averaged for successive shots of each subject and later for both groups of archers. The main difference between the elite and beginner archers was that the elite archers had a greater activation of the M. extensor digitorum, which indicates that they avoid gripping the bow-handle not only relaxing the flexor muscles, but also contracting the extensor muscle groups. This muscular contraction strategy secures the archer to not interfere with the forward movement of the bow, which is the forward acceleration of the bow caused by the pushing power of the bowstring.

  13. Eteplirsen in the treatment of Duchenne muscular dystrophy

    PubMed Central

    Lim, Kenji Rowel Q; Maruyama, Rika; Yokota, Toshifumi

    2017-01-01

    Duchenne muscular dystrophy is a fatal neuromuscular disorder affecting around one in 3,500–5,000 male births that is characterized by progressive muscular deterioration. It is inherited in an X-linked recessive fashion and is caused by loss-of-function mutations in the DMD gene coding for dystrophin, a cytoskeletal protein that stabilizes the plasma membrane of muscle fibers. In September 2016, the US Food and Drug Administration granted accelerated approval for eteplirsen (or Exondys 51), a drug that acts to promote dystrophin production by restoring the translational reading frame of DMD through specific skipping of exon 51 in defective gene variants. Eteplirsen is applicable for approximately 14% of patients with DMD mutations. This article extensively reviews and discusses the available information on eteplirsen to date, focusing on pharmacological, efficacy, safety, and tolerability data from preclinical and clinical trials. Issues faced by eteplirsen, particularly those relating to its efficacy, will be identified. Finally, the place of eteplirsen and exon skipping as a general therapeutic strategy in Duchenne muscular dystrophy treatment will be discussed. PMID:28280301

  14. Lipogenesis mitigates dysregulated sarcoplasmic reticulum calcium uptake in muscular dystrophy.

    PubMed

    Paran, Christopher W; Zou, Kai; Ferrara, Patrick J; Song, Haowei; Turk, John; Funai, Katsuhiko

    2015-12-01

    Muscular dystrophy is accompanied by a reduction in activity of sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) that contributes to abnormal Ca(2+) homeostasis in sarco/endoplasmic reticulum (SR/ER). Recent findings suggest that skeletal muscle fatty acid synthase (FAS) modulates SERCA activity and muscle function via its effects on SR membrane phospholipids. In this study, we examined muscle's lipid metabolism in mdx mice, a mouse model for Duchenne muscular dystrophy (DMD). De novo lipogenesis was ~50% reduced in mdx muscles compared to wildtype (WT) muscles. Gene expressions of lipogenic and other ER lipid-modifying enzymes were found to be differentially expressed between wildtype (WT) and mdx muscles. A comprehensive examination of muscles' SR phospholipidome revealed elevated phosphatidylcholine (PC) and PC/phosphatidylethanolamine (PE) ratio in mdx compared to WT mice. Studies in primary myocytes suggested that defects in key lipogenic enzymes including FAS, stearoyl-CoA desaturase-1 (SCD1), and Lipin1 are likely contributing to reduced SERCA activity in mdx mice. Triple transgenic expression of FAS, SCD1, and Lipin1 (3TG) in mdx myocytes partly rescued SERCA activity, which coincided with an increase in SR PE that normalized PC/PE ratio. These findings implicate a defect in lipogenesis to be a contributing factor for SERCA dysfunction in muscular dystrophy. Restoration of muscle's lipogenic pathway appears to mitigate SERCA function through its effects on SR membrane composition.

  15. Respiratory dysfunction in unsedated dogs with golden retriever muscular dystrophy.

    PubMed

    DeVanna, Justin C; Kornegay, Joe N; Bogan, Daniel J; Bogan, Janet R; Dow, Jennifer L; Hawkins, Eleanor C

    2014-01-01

    Golden retriever muscular dystrophy (GRMD) is a well-established model of Duchenne muscular dystrophy. The value of this model would be greatly enhanced with practical tools to monitor progression of respiratory dysfunction during treatment trials. Arterial blood gas analysis, tidal breathing spirometry, and respiratory inductance plethysmography (RIP) were performed to determine if quantifiable abnormalities could be identified in unsedated, untrained, GRMD dogs. Results from 11 dogs with a mild phenotype of GRMD and 11 age-matched carriers were compared. Arterial blood gas analysis was successfully performed in all dogs, spirometry in 21 of 22 (95%) dogs, and RIP in 18 of 20 (90%) dogs. Partial pressure of carbon dioxide and bicarbonate concentration were higher in GRMD dogs. Tidal breathing peak expiratory flows were markedly higher in GRMD dogs. Abnormal abdominal motion was present in 7 of 10 (70%) GRMD dogs. Each technique provided objective, quantifiable measures that will be useful for monitoring respiratory function in GRMD dogs during clinical trials while avoiding the influence of sedation on results. Increased expiratory flows and the pattern of abdominal breathing are novel findings, not reported in people with Duchenne muscular dystrophy, and might be a consequence of hyperinflation.

  16. Computational modeling of muscular thin films for cardiac repair

    NASA Astrophysics Data System (ADS)

    Böl, Markus; Reese, Stefanie; Parker, Kevin Kit; Kuhl, Ellen

    2009-03-01

    Motivated by recent success in growing biohybrid material from engineered tissues on synthetic polymer films, we derive a computational simulation tool for muscular thin films in cardiac repair. In this model, the polydimethylsiloxane base layer is simulated in terms of microscopically motivated tetrahedral elements. Their behavior is characterized through a volumetric contribution and a chain contribution that explicitly accounts for the polymeric microstructure of networks of long chain molecules. Neonatal rat ventricular cardiomyocytes cultured on these polymeric films are modeled with actively contracting truss elements located on top of the sheet. The force stretch response of these trusses is motivated by the cardiomyocyte force generated during active contraction as suggested by the filament sliding theory. In contrast to existing phenomenological models, all material parameters of this novel model have a clear biophyisical interpretation. The predictive features of the model will be demonstrated through the simulation of muscular thin films. First, the set of parameters will be fitted for one particular experiment documented in the literature. This parameter set is then used to validate the model for various different experiments. Last, we give an outlook of how the proposed simulation tool could be used to virtually predict the response of multi-layered muscular thin films. These three-dimensional constructs show a tremendous regenerative potential in repair of damaged cardiac tissue. The ability to understand, tune and optimize their structural response is thus of great interest in cardiovascular tissue engineering.

  17. LGS-AO Imaging of Every Kepler Planet Candidate: the Robo-AO KOI Survey

    NASA Astrophysics Data System (ADS)

    Baranec, Christoph; Law, Nicholas; Morton, Timothy; Ziegler, Carl; Nofi, Larissa; Atkinson, Dani; Riddle, Reed

    2015-12-01

    The Robo-AO Kepler Planetary Candidate Survey is observing every Kepler planet candidate host star with laser adaptive optics imaging, to search for blended nearby stars which may be physically associated companions and/or responsible for transit false positives. We will present the results from searching for companions around over 3,000 Kepler planet hosts in 2012-2015. We will describe our first data release covering 715 planet candidate hosts, and give a preview of ongoing results including improved statistics on the likelihood of false positive planet detections in the Kepler dataset, many new planets in multiple star systems, and new exotic multiple star systems containing Kepler planets. We will also describe the automated Robo-AO survey data reduction methods, including a method of using the large ensemble of target observations as mutual point-spread-function references, along with a new automated companion-detection algorithm designed for extremely large adaptive optics surveys. Our first data release covered 715 objects, searching for companions from 0.15” to 2.5” separation with contrast up to 6 magnitudes. We measured the overall nearby-star-probability for Kepler planet candidates to be 7.4+/-1.0%, and we will detail the variations in this number with stellar host parameters. We will also discuss plans to extend the survey to other transiting planet missions such as K2 and TESS as Robo-AO is in the process of being re-deployed to the 2.1-m telescope at Kitt Peak for 3 years and a higher-contrast Robo-AO system is being developed for the 2.2-m UH telescope on Maunakea.

  18. Review of AO calibrations, or how to best educate your AO system

    NASA Astrophysics Data System (ADS)

    Kolb, Johann

    2016-07-01

    If the Real-Time Computer is the heart of an AO system, the Wavefront Sensor (WFS) its eyes, the Deformable Mirror (DM) its hands and the control strategy its nervous system, the sum of all those parts is made into a harmonious entity thanks to calibrations. This paper does not have the ambition to provide an overview of all the currently existing calibration strategies, but rather to focus on a few challenging problems and their recent evolution in the era of adaptive telescopes, mostly based on the experience of ESO's Adaptive Optics Instruments in general and the AO Facility in particular. Single most important calibration in post-focal AO system, the recording of the Interaction Matrix (IM) between WFS and DM has since long evolved to use fast modulation techniques, has shown to be feasible on-sky and is now almost free from measurements thanks to its pseudo-synthetic generation, quasi-mandatory solution in an adaptive telescope. Pseudo- because it requires an unprecedented knowledge of the components' characteristics, especially the WFS, DM and the optical registration between the two. Bigger telescopes and the use of Laser Guide Stars (LGS) also mean that the properties of the system will change in time and thus need to be constantly updated thanks to online diagnosis tools for spot size measurement, atmosphere monitoring, Wavefront Sensing and control optimization. New loops come into play like the one to minimize LGS Jitter and the one taking over the telescope active optics by means of offloading the DM low orders, and they all require calibration. More calibration means more time and one has to carefully balance the calibrations that require precious telescope night time, day time or for the best, no telescope time at all. Their importance sometimes underestimated, calibrations have repeatedly shown to be a vital part in the optimum functioning of present and future AO systems.

  19. Directly Imaging Planets with SCExAO: First Results

    NASA Astrophysics Data System (ADS)

    Currie, Thayne M.; Guyon, Olivier; Jovanovic, Nemanja; Lozi, Julien; Tamura, Motohide; Kudo, Tomoyuki; Uyama, Taichi; Garcia, Eugenio

    2017-01-01

    We present the first science results from the newly commissioned Subaru Coronagraphic Extreme Adaptive Optics project, an experimental system dedicated to image faint jovian planets around nearby stars. SCExAO is now achieving true extreme AO capability. We describe the typical performance of SCExAO, the first images of benchmark exoplanets and planet-forming disks, and SCExAO’s first science results. Finally, we briefly chart the path forward for SCExAO to achieve its full scientific capability, including imaging mature planets in reflected light.

  20. Aerobic interval exercise with an eccentric contraction induces muscular hypertrophy and augmentation of muscular strength in rats.

    PubMed

    Tsumiyama, Wakako; Oki, Sadaaki; Takamiya, Naomi; Umei, Namiko; Shimizu, Michele Eisemann; Ono, Takeya; Otsuka, Akira

    2015-04-01

    [Purpose] The purpose of this study was to examine whether an aerobic interval exercise using an eccentric contraction would result in skeletal muscular hypertrophy and augmentation of muscular strength in rats. [Subjects and Methods] Twenty-one female Wistar rats were used in this study. The rats were randomly divided into three groups. The control group performed no exercise. The aerobic endurance exercise group ran for 90 min. The aerobic interval exercise group ran for a total of 90 minutes in 5 minute bouts separated by 2 minute rest periods. The exercise groups ran on a downhill treadmill incline, once every three days, for a total of twenty sessions. [Results] The muscle wet weights, the muscle fiber cross-section minor axes, and the tetanus tension results of the aerobic endurance and aerobic interval exercise groups were significantly larger than those of the control group. [Conclusion] These results indicate that aerobic interval exercise may be an effective method of inducing hypertrophy and augmenting muscular strength in skeletal muscle.

  1. Drive for muscularity is heightened in body-dissatisfied men who socially compare.

    PubMed

    Bucchianeri, Michaela M; Serrano, Jamie L; Pastula, Adrienne; Corning, Alexandra F

    2014-01-01

    Men's drive for muscularity refers to the degree to which men wish to increase their muscularity. Men who are more extreme in their drive for muscularity face dangerous consequences, such as increased levels of eating pathology and use of performance-enhancing substances. The aim of this study was to predict men's drive for muscularity, and to test whether hypothesized predictive factors vary across age groups. Participants were 226 men ages 18-67. It was hypothesized that body dissatisfaction would predict men's drive for muscularity. More substantively, however, it was hypothesized that having a strong tendency to compare oneself with others would exacerbate the relationship between men's body dissatisfaction and their drive for muscularity. Results of a hierarchical multiple regression analysis supported these hypotheses. Furthermore, this exacerbating effect was present regardless of men's age. Implications for assessment, clinical practice, research, and prevention efforts are discussed.

  2. Drive for muscularity and disordered eating among French adolescent boys: a sociocultural model.

    PubMed

    Rodgers, Rachel F; Ganchou, Camille; Franko, Debra L; Chabrol, Henri

    2012-06-01

    The pursuit of muscularity is an important body image concern among boys which has been described within sociocultural models of risk for eating disorders. This study explored a sociocultural model of disordered eating in which drive for thinness and pursuit of muscularity were both pathways to disordered eating among French adolescent boys. A sample of 146 adolescents completed a questionnaire assessing drive for thinness, drive for muscularity, media-ideal internalization, appearance comparison, and sociocultural pressure. The model was a good fit to the data and both drive for thinness and the pursuit of muscularity were related to disordered eating. Furthermore, internalization and appearance comparison mediated the relationships between pressure to increase muscle and both drive for muscularity and drive for thinness. Longitudinal research could help clarify the role of the pursuit of muscularity in the development of disordered eating and extreme body shape changing behaviors.

  3. The link between stress disorders and autonomic dysfunction in muscular dystrophy

    PubMed Central

    Sabharwal, Rasna

    2014-01-01

    Muscular dystrophy is a progressive disease of muscle weakness, muscle atrophy and cardiac dysfunction. Patients afflicted with muscular dystrophy exhibit autonomic dysfunction along with cognitive impairment, severe depression, sadness, and anxiety. Although the psychological aspects of cardiovascular disorders and stress disorders are well known, the physiological mechanism underlying this relationship is not well understood, particularly in muscular dystrophy. Therefore, the goal of this perspective is to highlight the importance of autonomic dysfunction and psychological stress disorders in the pathogenesis of muscular dystrophy. This article will for the first time—(i) outline autonomic mechanisms that are common to both psychological stress and cardiovascular disorders in muscular dystrophy; (ii) propose therapies that would improve behavioral and autonomic functions in muscular dystrophy. PMID:24523698

  4. Electromagnetic DM technology meets future AO demands

    NASA Astrophysics Data System (ADS)

    Hamelinck, Roger; Rosielle, Nick; Steinbuch, Maarten; Doelman, Niek

    New deformable mirror technology is developed by the Technische Universiteit Eindhoven, Delft University of Technology and TNO Science and Industry. Several prototype adaptive deformable mirrors are realized mirrors, up to 427 actuators and ∅150mm diameter, with characteristics suitable for future AO systems. The prototypes consist of a 100µm thick, continuous facesheet on which low voltage, electromagnetic, push-pull actuators impose out-of-plane displacements. The variable reluctance actuators with ±10µm stroke and nanometer resolution are located in a standard actuator module. Each module with 61 actuators connects to a single PCB with dedicated, 16 bit, PWM based, drivers. A LVDS multi-drop cable connects up to 32 actuator modules. With the actuator module, accompanying PCB and multi-drop system the deformable mirror technology is made modular in its mechanics and electronics. An Ethernet-LVDS bridge enables any commercial PC to control the mirror using the UDP standard. Latest results of the deformable mirror technology development are presented.

  5. [Features of bone and muscular diseases in accordance with physical exertion level in workers].

    PubMed

    Vlasova, E M; Alekseev, V B

    2012-01-01

    The authors studied changes in development and structure of bone and muscular disorders in industrial workers of Perm area. The workers' examination considered features of physical overload during the working process. The authors revealed developmental peculiarities of bone and muscular system in various occupational groups of metallurgists, oil extractors, machinery building workers. The article shows necessity of interdisciplinary approach and observation of the workers to prevent progression of bone and muscular disorders.

  6. Translational Studies of GALGT2 Gene Therapy for Duchenne Muscular Dystrophy

    DTIC Science & Technology

    2014-10-01

    Therapy for Duchenne Muscular Dystrophy PRINCIPAL INVESTIGATOR: Paul T. Martin, PhD CONTRACTING ORGANIZATION: The Research Institute...for Duchenne Muscular Dystrophy 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0416 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Paul T. Martin...translational studies in support of developing GALGT2 gene therapy for use in Duchenne Muscular dystrophy patients. In year 2, we have completed

  7. The Effect of Aging on Muscular Dynamics Underlying Movement Patterns Changes

    PubMed Central

    Vernooij, Carlijn A.; Rao, Guillaume; Berton, Eric; Retornaz, Frédérique; Temprado, Jean-Jacques

    2016-01-01

    Introduction: Aging leads to alterations not only within the complex subsystems of the neuro-musculo-skeletal system, but also in the coupling between them. Here, we studied how aging affects functional reorganizations that occur both within and between the behavioral and muscular levels, which must be coordinated to produce goal-directed movements. Using unimanual reciprocal Fitts' task, we examined the behavioral and muscular dynamics of older adults (74.4 ± 3.7 years) and compared them to those found for younger adults (23.2 ± 2.0 years). Methods: To achieve this objective, we manipulated the target size to trigger a phase transition in the behavioral regime and searched for concomitant signatures of a phase transition in the muscular coordination. Here, muscular coordination was derived by using the method of muscular synergy extraction. With this technique, we obtained functional muscular patterns through non-negative matrix factorization of the muscular signals followed by clustering the resulting synergies. Results: Older adults showed a phase transition in behavioral regime, although, in contrast to young participants, their kinematic profiles did not show a discontinuity. In parallel, muscular coordination displayed two typical signatures of a phase transition, that is, increased variability of coordination patterns and a reorganization of muscular synergies. Both signatures confirmed the existence of muscular reorganization in older adults, which is coupled with change in dynamical regime at behavioral level. However, relative to young adults, transition occurred at lower index of difficulty (ID) in older participants and the reorganization of muscular patterns lasted longer (over multiple IDs). Discussion: This implies that consistent changes occur in coordination processes across behavior and muscle. Furthermore, the repertoire of muscular patterns was reduced and somewhat modified for older adults, relative to young participants. This suggests that

  8. A Laboratory Experiment on Muscular Metabolism and Fatigue Using the Isolated Frog Muscle Preparation.

    ERIC Educational Resources Information Center

    Ianuzzo, C. David; And Others

    1987-01-01

    Describes an experiment which demonstrates the association of particular metabolic biochemical changes and muscular fatigue. Highlights applications related to cellular energy metabolism, metabolic regulation, and muscle energetics. (ML)

  9. NFIRAOS Multiconjugate AO System for TMT

    NASA Astrophysics Data System (ADS)

    Herriot, Glen; Andersen, David; Atwood, Jenny; Byrnes, Peter; Boyer, Corinne; Caputa, Kris; Correia, Carlos; Dunn, Jennifer; Ellerbroek, Brent; Fitzsimmons, Joeleff; Gilles, Luc; Hickson, Paul; Hill, Alexis; Pazder, John; Reshetov, Vlad; Smith, Malcolm; Véran, Jean-Pierre; Wang, Lianqi; Wevers, Ivan

    2011-09-01

    NFIRAOS, the Adaptive Optics system for the Thirty Meter Telescope, is a Multiconjugate Adaptive Optics System of order 60x60 with two deformable mirrors and six laser guide star wavefront sensors. NFIRAOS is 8 x 10 x 5 m (L x W x H) on a Nasmyth Platform and supports three client instruments operating over 0.8 - 2.5 μm wavelength range. In this paper we discuss: NFIRAOS' requirements and architecture; changes to NFIRAOS since the last AO4ELT conference; interior details of NFIRAOS; interfaces to instruments; integration and verification plans. Top-level science requirements include 50% sky coverage at the galactic pole with <187 nm wavefront error. Astrometry is an important science driver - to minimize image distortion, we have recently revised the optical design to use four off-axis paraboloidal mirrors. We have vastly simplified the laser WFS zoom optics and moved them inside the cold enclosure. To control image magnification, differential magnification and tip/tilt/focus, NFIRAOS' client instruments have three low-order warfront sensors monitoring near-infrared natural guide stars. These stars are sharpened by NFIRAOS, which assists sky coverage. NFIRAOS will have high throughput and low thermal background - it will be cooled to -30 °C. The insulated walls have a buried cold plate to intercept heat leakage and isothermalize the interior of NFIRAOS. Instruments have stringent requirements on heat leakage and must provide their own rotator and interface to NFIRAOS, including a rotating seal. For wavelength and flat field calibration of client instruments, a NFIRAOS Science Calibration Unit (NSCU) feeds light in the entrance window, through NFIRAOS, to instruments. Inside NFIRAOS are deployable light sources simulating natural and laser guide stars, a focal plane mask with pinholes illuminated by the NSCU, as well as a turbulence phase screen. A prototype screen has been manufactured by magneto-rheological machining. We are currently updating the NFIRAOS

  10. WIYN active optics: a platform for AO

    NASA Astrophysics Data System (ADS)

    Code, Arthur D.; Claver, Charles F.; Goble, Larry W.; Jacoby, George H.; Sawyer, David G.

    1998-09-01

    The WIYN 3.5 meter telescope is situated on the southwest ridge of Kitt Peak yielding excellent atmosphere seeing conditions. As such, the telescope and enclosure design was directed towards exploiting this feature. The primary mirror was spun cast and figured by the Steward Observatory Mirror Laboratory and the secondary mirror by Contraves. In both cases the performance exceeded the design specifications. The borosilicate primary is actively temperature controlled to within 0.2 C of the desired temperature, typically 0.5 degrees C below the ambient air. The telescope structure is also temperature controlled and the enclosure is opened to the outside ion all sides, which all heat sources are vented to ducts carrying air downwind of the facility. The primary mirror is actively controlled for low order aberrations by 66 axial actuators which are adjusted open loop via force matrix look-up tables and closed loop via real-time wavefront curvature sensing measurements. The active optics also included real-time collimation and focus control. The telescope drive and guider are capable of providing tracking to a few hundredths of a second of arc. By employing active telescope control at this level, it is possible to maintain telescope and local wavefront distortion to a level where atmospheric effects dominate the image quality. Since a significant fraction of the power in the atmospheric disturbances is contained in image motion the first step in adaptive optics control will be simple tip tilt. Studies of higher order AO system are being carried out, as well as additional test characterizing the telescope and site. It is intended to continue such studies in an attempt to establish long term variances.

  11. Robo-AO: Performance and Characterization at Palomar Observatory

    NASA Astrophysics Data System (ADS)

    Tendulkar, Shriharsh P.; Baranec, C.; Riddle, R. L.; Ramaprakash, A. N.; Law, N. M.; Kulkarni, S. R.; Dekany, R.; Bui, K.; Davis, J.; Burse, M.; Das, H.; Punnadi, S.; Chordia, P.

    2013-01-01

    Hosted at the Palomar 60-inch telescope, Robo-AO is the world's first completely autonomous, laser-beacon supported adaptive optics (AO) system, delivering diffraction-limited images in the visible and IR wavelengths. With simultaneous turbulence monitoring using a MASS-DIMM instrument, we have characterized the performance of Robo-AO as a function of local seeing, turbulence profile, laser return power and the brightness of the tip-tilt star. We shall present the various AO metrics: The full-width at half maxima of the point spread function, the Strehl ratio, the isoplanatic angle and their variations with the atmospheric and operating conditions. Strategies for optimizing robotic AO observations based on varying conditions will be discussed.

  12. Tracking the Development of Muscular Myoglobin Stores in Mysticete Calves

    PubMed Central

    Cartwright, Rachel; Newton, Cori; West, Kristi M.; Rice, Jim; Niemeyer, Misty; Burek, Kathryn; Wilson, Andrew; Wall, Alison N.; Remonida-Bennett, Jean; Tejeda, Areli; Messi, Sarah; Marcial-Hernandez, Lila

    2016-01-01

    For marine mammals, the ability to tolerate apnea and make extended dives is a defining adaptive trait, facilitating the exploitation of marine food resources. Elevated levels of myoglobin within the muscles are a consistent hallmark of this trait, allowing oxygen collected at the surface to be stored in the muscles and subsequently used to support extended dives. In mysticetes, the largest of marine predators, details on muscular myoglobin levels are limited. The developmental trajectory of muscular myoglobin stores has yet to be documented and any physiological links between early behavior and the development of muscular myoglobin stores remain unknown. In this study, we used muscle tissue samples from stranded mysticetes to investigate these issues. Samples from three different age cohorts and three species of mysticetes were included (total sample size = 18). Results indicate that in mysticete calves, muscle myoglobin stores comprise only a small percentage (17–23%) of conspecific adult myoglobin complements. Development of elevated myoglobin levels is protracted over the course of extended maturation in mysticetes. Additionally, comparisons of myoglobin levels between and within muscles, along with details of interspecific differences in rates of accumulation of myoglobin in very young mysticetes, suggest that levels of exercise may influence the rate of development of myoglobin stores in young mysticetes. This new information infers a close interplay between the physiology, ontogeny and early life history of young mysticetes and provides new insight into the pressures that may shape adaptive strategies in migratory mysticetes. Furthermore, the study highlights the vulnerability of specific age cohorts to impending changes in the availability of foraging habitat and marine resources. PMID:26788728

  13. Genetic epidemiology of muscular dystrophies resulting from sarcoglycan gene mutations.

    PubMed Central

    Fanin, M; Duggan, D J; Mostacciuolo, M L; Martinello, F; Freda, M P; Sorarù, G; Trevisan, C P; Hoffman, E P; Angelini, C

    1997-01-01

    BACKGROUND: The autosomal recessive limb-girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous muscle diseases characterised by progressive proximal limb muscle weakness. Six different loci have been mapped and pathogenetic mutations in the genes encoding the sarcoglycan complex components (alpha-, beta-, gamma-, and delta-sarcoglycan) have been documented. LGMD patients affected with primary "sarcoglycanopathies" are classified as LGMD2D, 2E, 2C, and 2F, respectively. METHODS: A geographical area in north east Italy (2,319,147 inhabitants) was selected for a genetic epidemiological study on primary sarcoglycanopathies. Within the period 1982 to 1996, all patients living in this region and diagnosed with muscular dystrophy were seen at our centre. Immunohistochemical and immunoblot screening for alpha-sarcoglycan protein deficiency was performed on all muscle biopsies from patients with a progressive muscular dystrophy of unknown aetiology and normal dystrophin. Sarcoglycan mutation analyses were conducted on all patient muscle biopsies shown to have complete or partial absence of alpha-sarcoglycan immunostaining or a decreased quantity of alpha-sarcoglycan protein on immunoblotting. RESULTS: Two hundred and four patient muscle biopsies were screened for alpha-sarcoglycan protein deficiency and 18 biopsies showed a deficiency. Pathogenetic mutations involving one gene for sarcoglycan complex components were identified in 13 patients: alpha-sarcoglycan in seven, beta-sarcoglycan in two, gamma-sarcoglycan in four, and none in the delta-sarcoglycan gene. The overall prevalence of primary sarcoglycanopathies, as of 31 December 1996, was estimated to be 5.6 x 10(-6) inhabitants. CONCLUSION: The prevalence rate estimated in this study is the first to be obtained after biochemical and molecular genetic screening for sarcoglycan defects. PMID:9429136

  14. Halofuginone improves muscle-cell survival in muscular dystrophies.

    PubMed

    Bodanovsky, Anna; Guttman, Noga; Barzilai-Tutsch, Hila; Genin, Ola; Levy, Oshrat; Pines, Mark; Halevy, Orna

    2014-07-01

    Halofuginone has been shown to prevent fibrosis via the transforming growth factor-β/Smad3 pathway in muscular dystrophies. We hypothesized that halofuginone would reduce apoptosis--the presumed cause of satellite-cell depletion during muscle degradation-in the mdx mouse model of Duchenne muscular dystrophy. Six-week-old mdx mouse diaphragm exhibited fourfold higher numbers of apoptotic nuclei compared with wild-type mice as determined by a TUNEL assay. Apoptotic nuclei were found in macrophages and in Pax7-expressing cells; some were located in centrally-nucleated regenerating myofibers. Halofuginone treatment of mdx mice reduced the apoptotic nuclei number in the diaphragm, together with reduction in Bax and induction in Bcl2 levels in myofibers isolated from these mice. A similar effect was observed when halofuginone was added to cultured myofibers. No apparent effect of halofuginone was observed in wild-type mice. Inhibition of apoptosis or staurosporine-induced apoptosis by halofuginone in mdx primary myoblasts and C2 myogenic cell line, respectively, was reflected by less pyknotic/apoptotic cells and reduced Bax expression. This reduction was reversed by a phosphinositide-3-kinase and mitogen-activated protein kinase/extracellular signal-regulated protein kinase inhibitors, suggesting involvement of these pathways in mediating halofuginone's effects on apoptosis. Halofuginone increased apoptosis in α smooth muscle actin- and prolyl 4-hydroxylase β-expressing cells in mdx diaphragm and in myofibroblasts, the major source of extracellular matrix. The data suggest an additional mechanism by which halofuginone improves muscle pathology and function in muscular dystrophies.

  15. Tracking the Development of Muscular Myoglobin Stores in Mysticete Calves.

    PubMed

    Cartwright, Rachel; Newton, Cori; West, Kristi M; Rice, Jim; Niemeyer, Misty; Burek, Kathryn; Wilson, Andrew; Wall, Alison N; Remonida-Bennett, Jean; Tejeda, Areli; Messi, Sarah; Marcial-Hernandez, Lila

    2016-01-01

    For marine mammals, the ability to tolerate apnea and make extended dives is a defining adaptive trait, facilitating the exploitation of marine food resources. Elevated levels of myoglobin within the muscles are a consistent hallmark of this trait, allowing oxygen collected at the surface to be stored in the muscles and subsequently used to support extended dives. In mysticetes, the largest of marine predators, details on muscular myoglobin levels are limited. The developmental trajectory of muscular myoglobin stores has yet to be documented and any physiological links between early behavior and the development of muscular myoglobin stores remain unknown. In this study, we used muscle tissue samples from stranded mysticetes to investigate these issues. Samples from three different age cohorts and three species of mysticetes were included (total sample size = 18). Results indicate that in mysticete calves, muscle myoglobin stores comprise only a small percentage (17-23%) of conspecific adult myoglobin complements. Development of elevated myoglobin levels is protracted over the course of extended maturation in mysticetes. Additionally, comparisons of myoglobin levels between and within muscles, along with details of interspecific differences in rates of accumulation of myoglobin in very young mysticetes, suggest that levels of exercise may influence the rate of development of myoglobin stores in young mysticetes. This new information infers a close interplay between the physiology, ontogeny and early life history of young mysticetes and provides new insight into the pressures that may shape adaptive strategies in migratory mysticetes. Furthermore, the study highlights the vulnerability of specific age cohorts to impending changes in the availability of foraging habitat and marine resources.

  16. Clinical and Laboratory Features Distinguishing Juvenile Polymyositis and Muscular Dystrophy

    PubMed Central

    MAMYROVA, GULNARA; KATZ, JAMES D.; JONES, ROBERT V.; TARGOFF, IRA N.; LACHENBRUCH, PETER A.; JONES, OLCAY Y.; MILLER, FREDERICK W.; RIDER, LISA G.

    2016-01-01

    Objective To differentiate juvenile polymyositis (PM) and muscular dystrophy, both of which may present with chronic muscle weakness and inflammation. Methods We studied 39 patients with probable or definite juvenile PM and 9 patients with muscular dystrophies who were initially misdiagnosed as having juvenile PM. Differences in demographic, clinical, and laboratory results; outcomes; and treatment responses were evaluated by Fisher’s exact and rank sum tests. Random forests classification analysis and logistic regression were performed to examine significant differences in multivariable models. Results Clinical features and serum muscle enzyme levels were similar between juvenile PM and dystrophy patients, except 89% of dystrophy patients had muscle atrophy compared with 46% of juvenile PM patients. Dystrophy patients had a longer delay to diagnosis (median 12 versus 4 months) and were less frequently hospitalized than juvenile PM patients (22% versus 74%). No dystrophy patients, but 54% of juvenile PM patients, had a myositis autoantibody. Dystrophy patients more frequently had myopathic features on muscle biopsy, including diffuse variation of myofiber size, fiber hypertrophy, and myofiber fibrosis (44–100% versus 8–53%). Juvenile PM patients more frequently had complex repetitive discharges on electromyography and a complete response to treatment with prednisone or other immunosuppressive agents than dystrophy patients (44% versus 0%). Random forests analysis revealed that the most important features in distinguishing juvenile PM from dystrophies were myositis autoantibodies, clinical muscle atrophy, and myofiber size variation on biopsy. Logistic regression confirmed muscle atrophy, myofiber fibrosis, and hospitalization as significant predictors. Conclusion Muscular dystrophy can present similarly to juvenile PM. Selected clinical and laboratory features are helpful in combination in distinguishing these conditions. PMID:23925923

  17. Physical management of muscular low back pain in the athlete.

    PubMed

    Smith, C F

    1977-09-17

    The Canadian medical staff at the 1976 Olympic Games found that muscular low back pain was a common problem among the athletes. The problem had usually developed during training as a result of neglect of certain anatomic areas, particularly the abdominal region. A five-point treatment and prevention program was used with good results. It included (a) relief of spasm and pain, (b) stretching, (c) exercise, (d) alteration of the training program and (e) education to prevent future problems or worsening of the present problem.

  18. Usefulness of myocardial strain imaging in Duchenne muscular dystrophy.

    PubMed

    Fayssoil, A

    2010-04-01

    Duchenne muscular dystrophy is an X-linked recessive disorder caused by the absence of dystrophin. Heart involvement is a classical complication in this disease and leads progressively to heart failure. Detecting latent myocardial involvement is essential in this disease because early use of drugs like angiotensin-converting enzyme inhibitors may delay the progression of heart disease. Myocardial strain imaging is an application of the tissue Doppler imaging. By assessing regional myocardial function, this tool might help clinicians to detect latent myocardial involvement in DMD patients.

  19. [Congenital unilateral muscular hyperplasia of the hand - a rare malformation].

    PubMed

    Pillukat, T; Lanz, U

    2004-01-01

    This is a report on eight cases of a rare congenital malformation in the upper extremity, consisting of a unilateral muscular hyperplasia. In addition to the hand, all segments of the upper extremity may be affected. The hyperplasia is always unilateral, preferably on the right hand side, in combination with accessory muscles. Hereditary dependence or association with other malformations has not been observed. Six of eight patients were male. Shoulder and arm function were normal in all cases. Ulnar drift of the fingers in the metacarpophalangeal joints (six of eight patients), flexion contractures of the metacarpophalangeal joints (six of eight patients) and extension contractures of the wrist (three of eight patients) to various degrees were seen. A prominence of the second and third metacarpal head with an enlarged space between them gave the affected hands a very typical appearance (six of eight patients). Deformities and functional limitations requiring surgical treatment were present in six patients. In all cases, accessory muscles were found intraoperatively and resected. The macroscopic and microscopic appearance of the muscle specimen did not differ from normal muscular tissue. In all cases, additional procedures were necessary to improve the overall function. Nevertheless, the reconstructive efforts did not lead to an entirely normal hand function or appearance. The malformation we describe can clearly be distinguished from other malformations such as arthrogryposis multiplex congenita, Freeman-Sheldon syndrome or macrodactyly. Up to now, only two other reports were found in the literature showing characteristics similar to those in our own cases. Four similar cases were observed by Benatar. From a pathomechanical point of view, a disturbance in the muscular balance seems to cause the deformities and functional limitations. This imbalance could be related to accessory muscles which are not opposed by defined antagonists or to an unbalanced hyperplasia of

  20. Cellular Therapies for Muscular Dystrophies: Frustrations and Clinical Successes.

    PubMed

    Negroni, Elisa; Bigot, Anne; Butler-Browne, Gillian S; Trollet, Capucine; Mouly, Vincent

    2016-02-01

    Cell-based therapy for muscular dystrophies was initiated in humans after promising results obtained in murine models. Early trials failed to show substantial clinical benefit, sending researchers back to the bench, which led to the discovery of many hurdles as well as many new venues to optimize this therapeutic strategy. In this review we summarize progress in preclinical cell therapy approaches, with a special emphasis on human cells potentially attractive for human clinical trials. Future perspectives for cell therapy in skeletal muscle are discussed, including the perspective of combined therapeutic approaches.

  1. Cardiac involvement in a female carrier of Duchenne muscular dystrophy.

    PubMed

    Walcher, Thomas; Kunze, Markus; Steinbach, Peter; Sperfeld, Anne-Dorte; Burgstahler, Christof; Hombach, Vinzenz; Torzewski, Jan

    2010-02-04

    A 42 year-old female carrier of Duchenne muscular dystrophy (DMD) was referred with suspected subacute myocarditis and non-sustained ventricular tachycardia. Echochardiography and cardiac catheterization revealed severely reduced left ventricular function (LVF). Coronary artery disease was excluded. Cardiac magnetic resonance imaging showed transmural, intramural and subepicardial late gadolinium enhancement. Myocardial biopsy excluded viral infection and showed severe myopathic changes with abnormal expression of dystrophin and utrophin. Moleculargenetic analysis of the DMD gene revealed frameshift duplication of exon 2. The patient received conventional heart failure therapy, implantable cardioverter/defibrillator-implantation and prednisolone to attenuate cardiac degradation. 6 months later she had improved clinically though LVF was still severely reduced.

  2. Fasciculations masquerading as minipolymyoclonus in bulbospinal muscular atrophy

    PubMed Central

    Bhat, Sushanth; Ma, Wei; Kozochonok, Elena; Chokroverty, Sudhansu

    2015-01-01

    Minipolymyoclonus has been described in both anterior horn cell disorders and central nervous system degenerative conditions. While its etiology remains unclear and speculative, a central generator has been previously proposed. We describe a case of bulbospinal muscular atrophy (Kennedy's disease), where minipolymyoclonus-like movements corresponded to fasciculations in neurophysiological studies. Our novel finding suggests that the etiologies of minipolymyoclonus in central and peripheral nervous system disorders are distinct, despite outward clinical similarity. The term “minipolyfasciculations” may be more reflective of the underlying process causing minipolymyoclonus-like movements in lower motor neuron disorders. PMID:26019432

  3. [First facioscapulohumeral muscular dystrophy prenatal diagnosis in a Bulgarian family].

    PubMed

    Buzhkov, B Ts; Vŭzharova, R; Dimitrova, V; Dimova, I; Tŭrnev, I; van der Wielen, M; van der Maarel, S; Bakker, B

    2005-01-01

    Facioscapulohumeral muscular dystrophy (FSHD) is the third most common myopathy. It is characterized by progressive descendent involvement of facial, shoulder girdle, truncal and lower extremities muscles. FSHD locus was mapped on the terminal part of the long arm of chromosome 4 (4q35). The disease is caused by a deletion of an integral number of tandem D4Z4 repeats and dimension of the pathological fragments < or = 38kb. Prenatal diagnosis of FSHD is possible but it is potentially difficult because of the big amount and high quality of DNA required. Hereby we describe the first prenatal tests performed for a Bulgarian family.

  4. Corticosteroid Treatment Impact on Spinal Deformity in Duchenne Muscular Dystrophy

    PubMed Central

    Sanzarello, Ilaria; Merlini, Luciano; Traina, Francesco; Rosa, Michele Attilio; Faldini, Cesare

    2014-01-01

    Duchenne muscular dystrophy is a progressive disease with loss of ambulation at around 9-10 years of age, followed, if untreated, by development of scoliosis, respiratory insufficiency, and death in the second decade of life. This review highlights the natural history of the disease, in particular, with regard to the development of the spinal deformity and how this complication has been modified by surgical interventions and overall by corticosteroid treatment. The beneficial effect of corticosteroids may have also an impact on the clinical trial design of the new emerging causative therapies. PMID:27382620

  5. The path to visible extreme adaptive optics with MagAO-2K and MagAO-X

    NASA Astrophysics Data System (ADS)

    Males, Jared R.; Close, Laird M.; Guyon, Olivier; Morzinski, Katie M.; Hinz, Philip; Esposito, Simone; Pinna, Enrico; Xompero, Marco; Briguglio, Runa; Riccardi, Armando; Puglisi, Alfio; Mazin, Ben; Ireland, Michael J.; Weinberger, Alycia; Conrad, Al; Kenworthy, Matthew; Snik, Frans; Otten, Gilles; Jovanovic, Nemanja; Lozi, Julien

    2016-07-01

    The next generation of extremely large telescopes (ELTs) have the potential to image habitable rocky planets, if suitably optimized. This will require the development of fast high order "extreme" adaptive optics systems for the ELTs. Located near the excellent site of the future GMT, the Magellan AO system (MagAO) is an ideal on-sky testbed for high contrast imaging development. Here we discuss planned upgrades to MagAO. These include improvements in WFS sampling (enabling correction of more modes) and an increase in speed to 2000 Hz, as well as an H2RG detector upgrade for the Clio infrared camera. This NSF funded project, MagAO-2K, is planned to be on-sky in November 2016 and will significantly improve the performance of MagAO at short wavelengths. Finally, we describe MagAO-X, a visible-wavelength extreme-AO "afterburner" system under development. MagAO-X will deliver Strehl ratios of over 80% in the optical and is optimized for visible light coronagraphy.

  6. AO 0235+164 and Surrounding Field: Surprising HST Results

    NASA Technical Reports Server (NTRS)

    Burbidge, E. M.; Beaver, E. A.; Cohen, Ross D.; Junkkarinen, V. T.; Lyons, R. W.

    1996-01-01

    Results obtained with the Hubble Space Telescope on the highly variable radio, x-ray, and gamma-ray emitting QSO (or BL Lac object) AO 0235 + 164 are presented and analyzed. WFPC2 images were obtained in 1994 June, when AO 0235 + 164 was bright (m approx. 17), and the results are described in Sec. 3. After subtraction of the PSF of the QSO, hereafter called AO following the nomenclature of Yanny et al. (1989), the companion object named A, 2 sec south of AO, is discovered not to be an elliptical galaxy as hypothesized earlier, but to be an AGN object, with a central UV-bright point-source nucleus and faint surrounding nebulosity extending to AO. The second companion object 1.3 sec east of AO discovered by Yanny et al. (1989) and named object Al, appears more like a normal spiral galaxy. We have measured the positions, luminosities, and colors of some 30 faint objects in the field around AO 0235 + 16; most are extended and may be star-forming galaxies in a loose group or cluster. Our most surprising result of the HST observations comes from FOS spectra obtained in 1995 July, discussed in Sec. 4. Because of a positioning error of the telescope and AO's faintness at that time (m approx. 20), object A was observed instead of the intended target AO. Serendipitously, we discovered A to have broad deep BALQSO-type absorptions of C IV, Si IV, N V shortward of broad emissions. A is thus ejecting high velocity, highly ionized gas into the surrounding IGM. We discuss in Sec. 5 the relationship of the objects in the central 10 sec X 1O sec region around AO, where redshifts z(sub e) = 0.94, z(sub a) = 0.524, 0.851 in AO, (sub e) = 0.524 and Z(sub BAL)=0.511 in A, are found. We hypothesize that some of the 30 faint objects in the 77 sec. x 77 sec. field may be part of a large star-forming region at z approx. 0.5, as suggested for a few objects by Yanny et al. (1989). The proximity of two highly active extragalactic objects, AO 0235+164 and its AGN companion A, is remarkable and

  7. The Relationship between Selected Body Composition Variables and Muscular Endurance in Women

    ERIC Educational Resources Information Center

    Esco, Michael R.; Olson, Michele S.; Williford, Henry N.

    2010-01-01

    The primary purpose of this study was to determine if muscular endurance is affected by referenced waist circumference groupings, independent of body mass and subcutaneous abdominal fat, in women. This study also explored whether selected body composition measures were associated with muscular endurance. Eighty-four women were measured for height,…

  8. Scalpel or Straitjacket: CRISPR/Cas9 Approaches for Muscular Dystrophies.

    PubMed

    Himeda, Charis L; Jones, Takako I; Jones, Peter L

    2016-04-01

    Versatility of CRISPR/Cas9-based platforms makes them promising tools for the correction of diverse genetic/epigenetic disorders. Here we contrast the use of these genome editing tools in two myopathies with very different molecular origins: Duchenne muscular dystrophy, a monogenetic disease, and facioscapulohumeral muscular dystrophy, an epigenetic disorder with unique therapeutic challenges.

  9. Some Dynamics of Personality Development in Boys Suffering from Muscular Dystrophy

    ERIC Educational Resources Information Center

    Mearig, Judith S.

    1973-01-01

    Discussed are personality aspects of Duchenne or pseudohypertrophic muscular dystrophy, a progressive wasting of muscular tissue, which afflicts only boys, and usually has its noticeable onset before the age of 6 years; and described is the development of three male dystrophic siblings. (DB)

  10. Meeting the Assistive Technology Needs of Students with Duchenne Muscular Dystrophy

    ERIC Educational Resources Information Center

    Heller, Kathryn Wolff; Mezei, Peter J.; Avant, Mary Jane Thompson

    2009-01-01

    Students with Duchenne muscular dystrophy (DMD) have a degenerative disease that requires ongoing changes in assistive technology (AT). The AT team needs to be knowledgeable about the disease and its progression in order to meet these students' changing needs in a timely manner. The unique needs of students with Duchenne muscular dystrophy in…

  11. A Cross-Sectional Study of School Experiences of Boys with Duchenne and Becker Muscular Dystrophy

    ERIC Educational Resources Information Center

    Soim, Aida; Lamb, Molly; Campbell, Kimberly; Pandya, Shree; Peay, Holly; Howard, James F., Jr.; Fox, Deborah

    2016-01-01

    The objectives of this study were to investigate types of supportive school services received and factors related to provision of these services. We conducted a cross-sectional study to describe the school experience of males with Duchenne and Becker muscular dystrophies. Study subjects were identified through the Muscular Dystrophy Surveillance,…

  12. Investigation of Poor Academic Achievement in Children with Duchenne Muscular Dystrophy

    ERIC Educational Resources Information Center

    Hinton, V. J.; De Vivo, D. C.; Fee, R.; Goldstein, E.; Stern, Y.

    2004-01-01

    Duchenne Muscular Dystrophy (DMD) is a neurogenetic developmental disorder that presents with progressive muscular weakness. It is caused by a mutation in a gene that results in the absence of specific products that normally localize to muscle cells and the central nervous system (CNS). The majority of affected individuals have IQs within the…

  13. Effects of Manual Negative Accentuated Resistance on Strength and/or Muscular Endurance.

    ERIC Educational Resources Information Center

    Johnson, Robert M.

    The purpose of this study was to determine the effects of manual negative accentuated resistance on strength and/or muscular endurance. Three strength and/or muscular endurance tests were administered to male and female physical education majors enrolled in a required exercise class at the beginning and end of the semester. Push-ups, chin-ups, and…

  14. Effects of Three Resistance Training Programs on Muscular Strength and Absolute and Relative Endurance.

    ERIC Educational Resources Information Center

    Anderson, Tim; Kearney, Jay T.

    1982-01-01

    The effects of three resistance training programs on male college students' muscular strength and absolute and relative muscular endurance were investigated. Results show that human skeletal muscle makes both general and specific adaptations to a training stimulus, and that the balance of these adaptations is to some extent dependent upon the…

  15. The Subaru Coronagraphic Extreme AO Project: Progress and Upgrades

    NASA Astrophysics Data System (ADS)

    Jovanovic, Nemanja; Martinache, F.; Guyon, O.; Clergeon, C.; Garrel, V.

    2013-01-01

    The Subaru Coronagraphic Extreme AO (SCExAO) instrument consists of a high performance Phase Induced Amplitude Apodisation (PIAA) coronagraph combined with an extreme Adaptive Optics (AO) system operating in the near-infrared (H band). The extreme AO system driven by the 2000 element deformable mirror will allow for Strehl ratios>90% to be achieved in the H-band when it goes closed loop. This makes the SCExAO instrument a powerful platform for high contrast imaging down to angular separations of the order of 1 λ/D. In this paper we report on the recent progress in regards to the development of the instrument, which includes the addition of a visible bench that makes use of the light at shorter wavelengths not currently utilized by SCExAO and closing the loop on the tip/tilt wavefront sensor. We will also discuss two exciting guest instruments which will expand the capabilities of SCExAO over the next few years; namely CHARIS which is a integral field spectrograph as well as VAMPIRES, a visible aperture masking experiment based on polarimetric analysis of circumstellar disks.

  16. Nitric oxide synthase deficiency and the pathophysiology of muscular dystrophy

    PubMed Central

    Tidball, James G; Wehling-Henricks, Michelle

    2014-01-01

    The secondary loss of neuronal nitric oxide synthase (nNOS) that occurs in dystrophic muscle is the basis of numerous, complex and interacting features of the dystrophic pathology that affect not only muscle itself, but also influence the interaction of muscle with other tissues. Many mechanisms through which nNOS deficiency contributes to misregulation of muscle development, blood flow, fatigue, inflammation and fibrosis in dystrophic muscle have been identified, suggesting that normalization in NO production could greatly attenuate diverse aspects of the pathology of muscular dystrophy through multiple regulatory pathways. However, the relative importance of the loss of nNOS from the sarcolemma versus the importance of loss of total nNOS from dystrophic muscle remains unknown. Although most current evidence indicates that nNOS localization at the sarcolemma is not required to achieve NO-mediated reductions of pathology in muscular dystrophy, the question remains open concerning whether membrane localization would provide a more efficient rescue from features of the dystrophic phenotype. PMID:25194047

  17. Thigh muscularity and strength in teenage soccer players.

    PubMed

    Hoshikawa, Y; Iida, T; Muramatsu, M; Ii, N; Nakajima, Y; Chumank, K; Kanehisa, H

    2013-05-01

    This study examined the thigh muscularity and strength capability in early adolescent soccer players. The cross-sectional areas (CSAs) of the thigh muscles and dynamic strength during knee extension and flexion at 1.05 rad/s were determined twice at an interval of 6 months in 24 male soccer players aged 12-13 years and 11 age- and body height-matched non-athletes. After 6 months, muscle CSA and dynamic strength increased without significant interaction of time and group. Thigh total muscle CSA was not significantly affected by group, but the value relative to either thigh CSA or body mass was higher in soccer players. While knee flexion strength was similar between the 2 groups, knee extension strength was greater in soccer players than in non-athletes, even in terms of strength relative to CSA. The current results indicate that, compared with age- and body height-matched non-athletes, early adolescent soccer players are characterized by higher relative distribution of muscle mass within the thigh and higher knee extension strength relative to the quadriceps CSA. During the growth stage in which body height begins to increase markedly, however, participation in competitive soccer training does not increase the rate of development in thigh muscularity and strength.

  18. The genetic basis of undiagnosed muscular dystrophies and myopathies

    PubMed Central

    Savarese, Marco; Di Fruscio, Giuseppina; Torella, Annalaura; Fiorillo, Chiara; Magri, Francesca; Fanin, Marina; Ruggiero, Lucia; Ricci, Giulia; Astrea, Guja; Passamano, Luigia; Ruggieri, Alessandra; Ronchi, Dario; Tasca, Giorgio; D'Amico, Adele; Janssens, Sandra; Farina, Olimpia; Mutarelli, Margherita; Marwah, Veer Singh; Garofalo, Arcomaria; Giugliano, Teresa; Sanpaolo, Simone; Del Vecchio Blanco, Francesca; Esposito, Gaia; Piluso, Giulio; D'Ambrosio, Paola; Petillo, Roberta; Musumeci, Olimpia; Rodolico, Carmelo; Messina, Sonia; Evilä, Anni; Hackman, Peter; Filosto, Massimiliano; Di Iorio, Giuseppe; Siciliano, Gabriele; Mora, Marina; Maggi, Lorenzo; Minetti, Carlo; Sacconi, Sabrina; Santoro, Lucio; Claes, Kathleen; Vercelli, Liliana; Mongini, Tiziana; Ricci, Enzo; Gualandi, Francesca; Tupler, Rossella; De Bleecker, Jan; Udd, Bjarne; Toscano, Antonio; Moggio, Maurizio; Pegoraro, Elena; Bertini, Enrico; Mercuri, Eugenio; Angelini, Corrado; Santorelli, Filippo Maria; Politano, Luisa; Bruno, Claudio; Comi, Giacomo Pietro

    2016-01-01

    Objective: To apply next-generation sequencing (NGS) for the investigation of the genetic basis of undiagnosed muscular dystrophies and myopathies in a very large cohort of patients. Methods: We applied an NGS-based platform named MotorPlex to our diagnostic workflow to test muscle disease genes with a high sensitivity and specificity for small DNA variants. We analyzed 504 undiagnosed patients mostly referred as being affected by limb-girdle muscular dystrophy or congenital myopathy. Results: MotorPlex provided a complete molecular diagnosis in 218 cases (43.3%). A further 160 patients (31.7%) showed as yet unproven candidate variants. Pathogenic variants were found in 47 of 93 genes, and in more than 30% of cases, the phenotype was nonconventional, broadening the spectrum of disease presentation in at least 10 genes. Conclusions: Our large DNA study of patients with undiagnosed myopathy is an example of the ongoing revolution in molecular diagnostics, highlighting the advantages in using NGS as a first-tier approach for heterogeneous genetic conditions. PMID:27281536

  19. Mitochondrial implications in bulbospinal muscular atrophy (Kennedy disease).

    PubMed

    Finsterer, Josef; Mishra, Anushree; Wakil, Salma; Pennuto, Maria; Soraru, Gianni

    2015-01-01

    There is increasing evidence that mitochondrial functions are secondarily disturbed in bulbospinal muscular atrophy (BSMA). This review focuses on the relation between BSMA and the effect of the expanded polyglutamine (poly-Q) androgen receptor (AR) on mitochondrial functions. Mitochondrial functions in bulbospinal muscular atrophy (SBMA) are affected on the molecular, clinical, and therapeutic level. On the molecular level there is down-regulation of various nuclear-DNA-encoded mitochondrial proteins by mutant androgen receptor (mAR), colocalization of the mAR with various mitochondrial proteins, association of mAR aggregates with mitochondria resulting in abnormal distribution of mitochondria, mtDNA depletion or multiple mtDNA deletions, mitochondrial membrane depolarization, increase in reactive oxidative species, and activation of the mitochondrial caspase pathway. On the clinical level various mitochondrial disorders mimic SBMA, and on the therapeutic level pioglitazone expresses PPAR-γ, cyclosporine-A restores mitochondrial membrane potentials, coenzyme-Q and idebenone reduce oxidative stress, and geldanamycin up-regulates protective mitochondrial heat shock proteins. In conclusion, in BSMA mitochondrial dysfunction results from various interactions of elongated poly-Q AR with mitochondria, mitochondrial proteins, nuclear or mitochondrial DNA, causing oxidative stress, decreased mitochondrial membrane potential, or activation of the mitochondrial caspase pathway. Additionally, mitochondrial disease may mimic BSMA and therapeutic approaches may depend on modifications of mitochondrial pathways.

  20. Numerical modelling of crural fascia mechanical interaction with muscular compartments.

    PubMed

    Pavan, Piero G; Pachera, Paola; Natali, Arturo N

    2015-05-01

    The interaction of the crural fascia with muscular compartments and surrounding tissues can be at the origin of different pathologies, such as compartment syndrome. This pathology consists in the onset of excessive intracompartmental pressure, which can have serious consequences for the patient, compromising blood circulation. The investigation of compartment syndrome etiology also takes into account the alteration of crural fascia mechanical properties as a cause of the syndrome, where the fascial stiffening would result in the rise of intracompartmental pressure. This work presents a computational approach toward evaluating some biomechanical aspects of the problem, within the context of a more global viewpoint. Finite element analyses of the interaction phenomena of the crural fascia with adjacent regions are reported here. This study includes the effects of a fascial stiffness increase along the proximal-distal direction and their possible clinical implications. Furthermore, the relationship between different pre-strain levels of the crural fascia in the proximal-distal direction and the rise of internal pressure in muscular compartments are considered. The numerical analyses can clarify which aspects could be directly implied in the rise of compartment syndrome, leading to greater insight into muscle-fascia mechanical phenomena, as well as promoting experimental investigation and clinical analysis of the syndrome.

  1. Dystrophin in frameshift deletion patients with Becker Muscular Dystrophy

    SciTech Connect

    Gangopadhyay, S.B.; Ray, P.N.; Worton, R.G.; Sherratt, T.G.; Heckmatt, J.Z.; Dubowitz, V.; Strong, P.N.; Miller, G. ); Shokeir, M. )

    1992-09-01

    In a previous study the authors identified 14 cases with Duchenne muscular dystrophy (DMD) or its milder variant, Becker muscular dystrophy (BMD), with a deletion of exons 3-7, a deletion that would be expected to shift the translational reading frame of the mRNA and give a severe phenotype. They have examined dystrophin and its mRNA from muscle biopsies of seven cases with either mild or intermediate phenotypes. In all cases they detected slightly lower-molecular-weight dystrophin in 12%-15% abundance relative to the normal. By sequencing amplified mRNA they have found that exon 2 is spliced to exon 8, a splice that produces a frameshifted mRNA, and have found no evidence for alternate splicing that might be involved in restoration of dystrophin mRNA reading frame in the patients with a mild phenotype. Other transcriptional and posttranscriptional mechanisms such as cryptic promoter, ribosomal frameshifting, and reinitiation are suggested that might play some role in restoring the reading frame. 34 refs., 5 figs. 1 tab.

  2. Dystrophin-deficient muscular dystrophy in a Norfolk terrier.

    PubMed

    Beltran, E; Shelton, G D; Guo, L T; Dennis, R; Sanchez-Masian, D; Robinson, D; De Risio, L

    2015-05-01

    A six-month-old male entire Norfolk terrier was presented with a 3-month history of poor development, reluctance to exercise and progressive and diffuse muscle atrophy. Serum creatine kinase concentration was markedly elevated. Magnetic resonance imaging of the epaxial muscles revealed asymmetrical streaky signal changes aligned within the muscle fibres (hyperintense on T2-weighted images and short-tau inversion recovery with moderate contrast enhancement on T1-weighted images). Electromyography revealed pseudomyotonic discharges and fibrillation potentials localised at the level of the supraspinatus, epaxial muscles and tibial cranialis muscles. Muscle biopsy results were consistent with dystrophin-deficient muscular dystrophy. The dog remained stable 7 months after diagnosis with coenzyme Q10 and l-carnitine; however after that time, there was a marked deterioration and the owners elected euthanasia. This case report describes the clinical presentation, magnetic resonance imaging, electrodiagnostic and histopathological findings with immunohistochemical analysis in a Norfolk terrier with confirmed dystrophin-deficient muscular dystrophy, which has not been previously described in this breed.

  3. Facioscapulohumeral muscular dystrophy in mice overexpressing FRG1.

    PubMed

    Gabellini, Davide; D'Antona, Giuseppe; Moggio, Maurizio; Prelle, Alessandro; Zecca, Chiara; Adami, Raffaella; Angeletti, Barbara; Ciscato, Patrizia; Pellegrino, Maria Antonietta; Bottinelli, Roberto; Green, Michael R; Tupler, Rossella

    2006-02-23

    Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disorder that is not due to a classical mutation within a protein-coding gene. Instead, almost all FSHD patients carry deletions of an integral number of tandem 3.3-kilobase repeat units, termed D4Z4, located on chromosome 4q35 (ref. 3). D4Z4 contains a transcriptional silencer whose deletion leads to inappropriate overexpression in FSHD skeletal muscle of 4q35 genes located upstream of D4Z4 (ref. 4). To identify the gene responsible for FSHD pathogenesis, we generated transgenic mice selectively overexpressing in skeletal muscle the 4q35 genes FRG1, FRG2 or ANT1. We find that FRG1 transgenic mice develop a muscular dystrophy with features characteristic of the human disease; by contrast, FRG2 and ANT1 transgenic mice seem normal. FRG1 is a nuclear protein and several lines of evidence suggest it is involved in pre-messenger RNA splicing. We find that in muscle of FRG1 transgenic mice and FSHD patients, specific pre-mRNAs undergo aberrant alternative splicing. Collectively, our results suggest that FSHD results from inappropriate overexpression of FRG1 in skeletal muscle, which leads to abnormal alternative splicing of specific pre-mRNAs.

  4. Spinal muscular atrophy: from tissue specificity to therapeutic strategies

    PubMed Central

    Iascone, Daniel M.; Lee, Justin C.

    2015-01-01

    Spinal muscular atrophy (SMA) is the most frequent genetic cause of death in infants and toddlers. All cases of spinal muscular atrophy result from reductions in levels of the survival motor neuron (SMN) protein, and so SMN upregulation is a focus of many preclinical and clinical studies. We examine four issues that may be important in planning for therapeutic success. First, neuromuscular phenotypes in the SMNΔ7 mouse model closely match those in human patients but peripheral disease manifestations differ, suggesting that endpoints other than mouse lifespan may be more useful in predicting clinical outcome. Second, SMN plays important roles in multiple central and peripheral cell types, not just motor neurons, and it remains unclear which of these cell types need to be targeted therapeutically. Third, should SMN-restoration therapy not be effective in all patients, blocking molecular changes downstream of SMN reduction may confer significant benefit, making it important to evaluate therapeutic targets other than SMN. Lastly, for patients whose disease progression is slowed, but who retain significant motor dysfunction, additional approaches used to enhance regeneration of the neuromuscular system may be of value. PMID:25705387

  5. Elevated satellite cell number in Duchenne muscular dystrophy.

    PubMed

    Kottlors, Michael; Kirschner, Janbernd

    2010-06-01

    The regenerative potential of muscle tissue relies mostly on satellite cells situated between the muscular basal membrane and the sarcolemma. The regeneration of muscle tissue comprises proliferation, the propagation of satellite cells, and their subsequent differentiation with the expression of multiple muscle-specific proteins. However, in Duchenne muscular dystrophy (DMD), regeneration cannot compensate for the loss of muscle tissue. To examine the regenerative potential in DMD, satellite cell nuclei number and markers of differentiation in DMD muscle from various disease states were compared with control muscle. Differentiation of satellite cells is characterized by the helix-loop-helix factor myogenin, which is never co-expressed with Pax7, whereas MyoD1 and Myf5 are co-expressed with Pax7, with Myf5 being present even in muscle of controls. The results indicate that satellite cell number is elevated in DMD in comparison with control muscle, even in advanced stages of dystrophy, suggesting that exhaustion of satellite cells is not the primary cause for failed regeneration. The expression of myogenin is correlated neither with fibrosis nor with age. We suggest variable factors influencing the differentiation of satellite cells in DMD.

  6. Morphometric studies of the muscular branch of the median nerve.

    PubMed Central

    Olave, E; Prates, J C; Gabrielli, C; Pardi, P

    1996-01-01

    The branch from the median nerve to the thenar muscles has a proximal and lateral (recurrent) course and is vulnerable to lesions that affect these muscles. Because of its anatomical-clinical importance, this branch was studied in 60 palmar regions from 30 cadavers of adult individuals of both sexes, aged between 23 and 77 y. It arose from the lateral branch of the median nerve in 83.3% of the cases. Its origin was distal to the flexor retinaculum in 48.3%, at the distal margin of the retinaculum in 31.6%, in the carpal tunnel in 18.3% and proximal to the retinaculum in 1.7%; it pierced the retinaculum in 15%. The point of recurrence of the branch was localised topographically to 34.6 +/- 3.6 mm from the distal wrist crease; the angle between its recurrent course and the longitudinal axis of the hand averaged 66.8 degrees. In 50% of the cases the muscular branch innervated abductor pollicis brevis (APB), opponens pollicis (OP) and the superficial head of flexor pollicis brevis (FPB), in 40% it supplied only APB and OP, and in 10% a short muscular branch gave rise to independent branches in the palm and which supplied APB, OP and the superficial head of FPB. The so called "accessory thenar branch' was found in 38.3%. Images Fig. 1 Fig. 2 PMID:8886966

  7. Saccadic eye movements are impaired in Duchenne muscular dystrophy.

    PubMed

    Lui, F; Fonda, S; Merlini, L; Corazza, R

    2001-11-01

    Extraocular muscles are generally considered to be spared in Duchenne Muscular Dystrophy (DMD). However, this assumption is based mainly on clinical observations, as systematic eye movement recordings have been performed in a very limited number of cases. Our goal was to analyze several saccade parameters in a higher number of cases, in order to reveal a possible ocular-motor impairment in DMD. Data were collected from a population of 9 subjects with DMD and 9 healthy male subjects of comparable age as controls. We used the electrooculographic (EOG) technique coupled with advanced digital signal processing; saccade duration, amplitude, mean velocity, peak velocity and K factor (ratio mean/peak velocity) were measured. The DMD group showed saccades with significantly longer duration and lower velocity, with respect to controls; these differences were accounted for mainly by the largest movements, whereas there were no significant differences at the smallest eccentricity tested (3 deg). Neither amplitude nor K factor were significantly different from controls for any of the eccentricities tested. To our knowledge. this is the first study to suggest significant impairment of eye movements in Duchenne muscular dystrophy.

  8. Reassessing the improbability of a muscular crinoid stem

    NASA Astrophysics Data System (ADS)

    Gorzelak, Przemysław; Głuchowski, Edward; Salamon, Mariusz A.

    2014-08-01

    Muscular articulations in modern stalked crinoids are only present in the arms. Although it has been suggested that certain coiled-stemmed fossil taxa may have been functionally adapted to utilize muscles, evidence supporting this interpretation is lacking. Here, we use cathodoluminescence and SEM to reveal the skeletal microstructure of the enigmatic coiled-stemmed taxon Ammonicrinus (Flexibilia). Based on the well-established link between skeletal microstructure and the nature of infilling soft tissues in modern echinoderms, we reconstructed the palaeoanatomy of the Middle Devonian ammonicrinids. We show that their median columnals with elongated lateral columnal enclosure extensions (LCEE) have stereom microstructure unexpectedly resembling that in the crinoid muscular arm plates. In particular, large ligamentary facets, that are present on each side of a transverse ridge, are mainly comprised of fine galleried stereom that is indicative of the mutable collagenous tissues. In contrast, fine labyrinthic stereom, commonly associated with muscles, is situated in the periphery on each side of the surface of elongated LCEE. Our findings thus strongly suggest that the muscles may have also been present in the stem of ammonicrinids. These results reassess the previous hypotheses about evolution of muscles in crinoids and provide new insights into the mode of life of Ammonicrinus.

  9. Identification of muscle-specific microRNAs in serum of muscular dystrophy animal models: promising novel blood-based markers for muscular dystrophy.

    PubMed

    Mizuno, Hideya; Nakamura, Akinori; Aoki, Yoshitsugu; Ito, Naoki; Kishi, Soichiro; Yamamoto, Kazuhiro; Sekiguchi, Masayuki; Takeda, Shin'ichi; Hashido, Kazuo

    2011-03-30

    Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder caused by mutations in the dystrophin gene, which encodes a cytoskeletal protein, dystrophin. Creatine kinase (CK) is generally used as a blood-based biomarker for muscular disease including DMD, but it is not always reliable since it is easily affected by stress to the body, such as exercise. Therefore, more reliable biomarkers of muscular dystrophy have long been desired. MicroRNAs (miRNAs) are small, ∼22 nucleotide, noncoding RNAs which play important roles in the regulation of gene expression at the post-transcriptional level. Recently, it has been reported that miRNAs exist in blood. In this study, we hypothesized that the expression levels of specific serum circulating miRNAs may be useful to monitor the pathological progression of muscular diseases, and therefore explored the possibility of these miRNAs as new biomarkers for muscular diseases. To confirm this hypothesis, we quantified the expression levels of miRNAs in serum of the dystrophin-deficient muscular dystrophy mouse model, mdx, and the canine X-linked muscular dystrophy in Japan dog model (CXMD(J)), by real-time PCR. We found that the serum levels of several muscle-specific miRNAs (miR-1, miR-133a and miR-206) are increased in both mdx and CXMD(J). Interestingly, unlike CK levels, expression levels of these miRNAs in mdx serum are little influenced by exercise using treadmill. These results suggest that serum miRNAs are useful and reliable biomarkers for muscular dystrophy.

  10. Biological, Psychological, and Sociocultural Factors Contributing to the Drive for Muscularity in Weight-Training Men.

    PubMed

    Schneider, Catharina; Rollitz, Laura; Voracek, Martin; Hennig-Fast, Kristina

    2016-01-01

    The drive for muscularity and associated behaviors (e.g., exercising and dieting) are of growing importance for men in Western societies. In its extreme form, it can lead to body image concerns and harmful behaviors like over-exercising and the misuse of performance-enhancing substances. Therefore, investigating factors associated with the drive for muscularity, especially in vulnerable populations like bodybuilders and weight trainers can help identify potential risk and protective factors for body image problems. Using a biopsychosocial framework, the aim of the current study was to explore different factors associated with drive for muscularity in weight-training men. To this purpose, German-speaking male weight trainers (N = 248) completed an online survey to determine the extent to which biological, psychological, and sociocultural factors contribute to drive for muscularity and its related attitudes and behaviors. Using multiple regression models, findings showed that media ideal body internalization was the strongest positive predictor for drive for muscularity, while age (M = 25.9, SD = 7.4) held the strongest negative association with drive for muscularity. Dissatisfaction with muscularity, but not with body fat, was related to drive for muscularity. The fat-free mass index, a quantification of the actual degree of muscularity of a person, significantly predicted drive for muscularity-related behavior but not attitudes. Body-related aspects of self-esteem, but not global self-esteem, were significant negative predictors of drive for muscularity. Since internalization of media body ideals presented the highest predictive value for drive for muscularity, these findings suggest that media body ideal internalizations may be a risk factor for body image concerns in men, leading, in its most extreme form to disordered eating or muscle dysmorphia. Future research should investigate the relations between drive for muscularity, age, body composition

  11. Biological, Psychological, and Sociocultural Factors Contributing to the Drive for Muscularity in Weight-Training Men

    PubMed Central

    Schneider, Catharina; Rollitz, Laura; Voracek, Martin; Hennig-Fast, Kristina

    2016-01-01

    The drive for muscularity and associated behaviors (e.g., exercising and dieting) are of growing importance for men in Western societies. In its extreme form, it can lead to body image concerns and harmful behaviors like over-exercising and the misuse of performance-enhancing substances. Therefore, investigating factors associated with the drive for muscularity, especially in vulnerable populations like bodybuilders and weight trainers can help identify potential risk and protective factors for body image problems. Using a biopsychosocial framework, the aim of the current study was to explore different factors associated with drive for muscularity in weight-training men. To this purpose, German-speaking male weight trainers (N = 248) completed an online survey to determine the extent to which biological, psychological, and sociocultural factors contribute to drive for muscularity and its related attitudes and behaviors. Using multiple regression models, findings showed that media ideal body internalization was the strongest positive predictor for drive for muscularity, while age (M = 25.9, SD = 7.4) held the strongest negative association with drive for muscularity. Dissatisfaction with muscularity, but not with body fat, was related to drive for muscularity. The fat-free mass index, a quantification of the actual degree of muscularity of a person, significantly predicted drive for muscularity-related behavior but not attitudes. Body-related aspects of self-esteem, but not global self-esteem, were significant negative predictors of drive for muscularity. Since internalization of media body ideals presented the highest predictive value for drive for muscularity, these findings suggest that media body ideal internalizations may be a risk factor for body image concerns in men, leading, in its most extreme form to disordered eating or muscle dysmorphia. Future research should investigate the relations between drive for muscularity, age, body composition

  12. Drive for thinness and drive for muscularity: opposite ends of the continuum or separate constructs?

    PubMed

    Kelley, Courtney C Galliger; Neufeld, Jennie M; Musher-Eizenman, Dara R

    2010-01-01

    The goal of this study was to examine whether the drive for thinness and the drive for muscularity occur concurrently among late adolescents and to understand the body attitudes associated with desiring a thinner and/or a more muscular physique. Participants included 235 college freshmen who participated in a larger study of body image and eating attitudes. The majority of individuals reported having both a high drive for thinness and a high drive for muscularity (65.4%). Additionally, the presence of both drives significantly predicted body compulsivity and body anxiety among females, and body-esteem among males. Results of the current study provide considerable evidence that a drive for thinness and a drive for muscularity are not mutually exclusive. Furthermore, the degree to which an individual strives for thinness and/or muscularity has differential effects on their body attitudes.

  13. Trends with corticosteroid use in males with Duchenne muscular dystrophy born 1982-2001.

    PubMed

    Fox, Deborah J; Kumar, Anil; West, Nancy A; DiRienzo, A Gregory; James, Katherine A; Oleszek, Joyce

    2015-01-01

    This study examines trends in corticosteroid use for males with Duchenne muscular dystrophy by birth year, race/ethnicity, and knowledge of Duchenne muscular dystrophy family history. Firstborn males (n = 521) selected from a population-based surveillance system of Duchenne muscular dystrophy were analyzed using Kaplan Meier and regression methods. Comparing males born 1982 to 1986 with males born 1997 to 2001, steroid use increased from 54% to 72% and mean age at steroid initiation decreased from 8.2 to 7.1 years. Hispanics and non-Hispanic Black males used steroids less frequently and delayed initiation compared to white males. Compared to males without a Duchenne muscular dystrophy family history, males with known family history were half as likely to use steroids. Duration of steroid use increased over time and age at initiation decreased. Racial/ethnic disparities exist for steroid use and should be addressed to improve outcome and quality of life for boys with Duchenne muscular dystrophy.

  14. Gaming magazines and the drive for muscularity in preadolescent boys: a longitudinal examination.

    PubMed

    Harrison, Kristen; Bond, Bradley J

    2007-09-01

    The development of a drive for muscularity among boys has been linked to various cultural influences, one of which is exposure to mass media depicting the muscular male body ideal. We sought to determine whether self-reported exposure to four ideal-body magazine genres (health/fitness, fashion, sports, and gaming) predicted an increased drive for muscularity 1 year later. A sample of 104 Black and 77 White preadolescent boys (mean age 8.77) participated in a 2-wave longitudinal panel study. Controlling Wave 1 grade, perceived thinness/adiposity, and drive for muscularity, exposure to video gaming magazines predicted a significant increase in Wave 2 drive for muscularity, but only for White boys. Discussion calls for the inclusion of video gaming magazine exposure measures in future research on print media and male body ideals, along with empirical exploration of racial themes in gaming magazines.

  15. SCExAO: First Results and On-Sky Performance

    NASA Astrophysics Data System (ADS)

    Currie, Thayne; Guyon, Olivier; Martinache, Frantz; Clergeon, Christophe; McElwain, Michael; Thalmann, Christian; Jovanovic, Nemanja; Singh, Garima; Kudo, Tomoyuki

    2014-01-01

    We present new on-sky results for the Subaru Coronagraphic Extreme Adaptive Optics imager (SCExAO) verifying and quantifying the contrast gain enabled by key components: the closed-loop coronagraphic low-order wavefront sensor (CLOWFS) and focal plane wavefront control (``speckle nulling''). SCExAO will soon be coupled with a high-order, Pyramid wavefront sensor which will yield > 90% Strehl ratio and enable 106-107 contrast at small angular separations allowing us to image gas giant planets at solar system scales. Upcoming instruments like VAMPIRES, FIRST, and CHARIS will expand SCExAO's science capabilities.

  16. SCExAO: First Results and On-Sky Performance

    NASA Technical Reports Server (NTRS)

    Currie, Thayne; Guyon, Olivier; Martinache, Frantz; Clergeon, Christophe; McElwain, Michael; Thalmann, Christian; Jovanovic, Nemanja; Singh, Garima; Kudo, Tomoyuki

    2013-01-01

    We present new on-sky results for the Subaru Coronagraphic Extreme Adaptive Optics imager (SCExAO) verifying and quantifying the contrast gain enabled by key components: the closed-loop coronagraphic low-order wavefront sensor (CLOWFS) and focal plane wavefront control ("speckle nulling"). SCExAO will soon be coupled with a high-order, Pyramid wavefront sensor which will yield greater than 90% Strehl ratio and enable 10(exp 6) -10(exp 7) contrast at small angular separations allowing us to image gas giant planets at solar system scales. Upcoming instruments like VAMPIRES, FIRST, and CHARIS will expand SCExAO's science capabilities.

  17. The Robo-AO automated intelligent queue system

    NASA Astrophysics Data System (ADS)

    Riddle, Reed L.; Hogstrom, Kristina; Papadopoulos, Athanasios; Baranec, Christoph; Law, Nicholas M.

    2014-07-01

    Robo-AO is the first automated laser adaptive optics instrument. In just its second year of scientific operations, it has completed the largest adaptive optics surveys to date, each comprising thousands of targets. Robo-AO uses a fully automated queue scheduling system that selects targets based on criteria entered on a per observing program or per target basis, and includes the ability to coordinate with US Strategic Command automatically to avoid lasing space assets. This enables Robo-AO to select among thousands of targets at a time, and achieve an average observation rate of approximately 20 targets per hour.

  18. Developmental Defects in a Zebrafish Model for Muscular Dystrophies Associated with the Loss of Fukutin-Related Protein (FKRP)

    ERIC Educational Resources Information Center

    Thornhill, Paul; Bassett, David; Lochmuller, Hanns; Bushby, Kate; Straub, Volker

    2008-01-01

    A number of muscular dystrophies are associated with the defective glycosylation of [alpha]-dystroglycan and many are now known to result from mutations in a number of genes encoding putative or known glycosyltransferases. These diseases include severe forms of congenital muscular dystrophy (CMD) such as Fukuyama type congenital muscular dystrophy…

  19. Air stacking: effects on pulmonary function in patients with spinal muscular atrophy and in patients with congenital muscular dystrophy*,**

    PubMed Central

    Marques, Tanyse Bahia Carvalho; Neves, Juliana de Carvalho; Portes, Leslie Andrews; Salge, João Marcos; Zanoteli, Edmar; Reed, Umbertina Conti

    2014-01-01

    OBJECTIVE: Respiratory complications are the main causes of morbidity and mortality in patients with neuromuscular disease (NMD). The objectives of this study were to determine the effects that routine daily home air-stacking maneuvers have on pulmonary function in patients with spinal muscular atrophy (SMA) and in patients with congenital muscular dystrophy (CMD), as well as to identify associations between spinal deformities and the effects of the maneuvers. METHODS: Eighteen NMD patients (ten with CMD and eight with SMA) were submitted to routine daily air-stacking maneuvers at home with manual resuscitators for four to six months, undergoing pulmonary function tests before and after that period. The pulmonary function tests included measurements of FVC; PEF; maximum insufflation capacity (MIC); and assisted and unassisted peak cough flow (APCF and UPCF, respectively) with insufflations. RESULTS: After the use of home air-stacking maneuvers, there were improvements in the APCF and UPCF. In the patients without scoliosis, there was also a significant increase in FVC. When comparing patients with and without scoliosis, the increases in APCF and UPCF were more pronounced in those without scoliosis. CONCLUSIONS: Routine daily air-stacking maneuvers with a manual resuscitator appear to increase UPCF and APCF in patients with NMD, especially in those without scoliosis. PMID:25410841

  20. Translating golden retriever muscular dystrophy microarray findings to novel biomarkers for cardiac/skeletal muscle function in Duchenne Muscular Dystrophy

    PubMed Central

    Galindo, Cristi L.; Soslow, Jonathan H.; Brinkmeyer-Langford, Candice L.; Gupte, Manisha; Smith, Holly M.; Sengsayadeth, Seng; Sawyer, Douglas B.; Benson, D. Woodrow; Kornegay, Joe N.; Markham, Larry W.

    2016-01-01

    Background In Duchenne muscular dystrophy (DMD), abnormal cardiac function is typically preceded by a decade of skeletal muscle disease. Molecular reasons for differences in onset and progression of these muscle groups are unknown. Human biomarkers are lacking. Methods We analyzed cardiac and skeletal muscle microarrays from normal and golden retriever muscular dystrophy (GRMD) dogs (ages 6, 12, or 47+ months) to gain insight into muscle dysfunction and to identify putative DMD biomarkers. These biomarkers were then measured using human DMD blood samples. Results We identified GRMD candidate genes that might contribute to the disparity between cardiac and skeletal muscle disease, focusing on brain-derived neurotropic factor (BDNF) and osteopontin (OPN/SPP1). BDNF was elevated in cardiac muscle of younger GRMD but was unaltered in skeletal muscle, while SPP1 was increased only in GRMD skeletal muscle. In human DMD, circulating levels of BDNF were inversely correlated with ventricular function and fibrosis, while SPP1 levels correlated with skeletal muscle function. Conclusion These results highlight gene expression patterns that could account for differences in cardiac and skeletal disease in GRMD. Most notably, animal model-derived data were translated to DMD and support use of BDNF and SPP1 as biomarkers for cardiac and skeletal muscle involvement, respectively. PMID:26672735

  1. LGS-AO Imaging of Every Kepler Planet Candidate: the Robo-AO KOI Survey

    NASA Astrophysics Data System (ADS)

    Law, Nicholas Michael; Baranec, Christoph; Morton, Timothy; Ziegler, Carl; Atkinson, Dani; Riddle, Reed

    2015-08-01

    The Robo-AO Kepler Planetary Candidate Survey is observing every Kepler planet candidate host star with laser adaptive optics imaging, to search for blended nearby stars which may be physically associated companions and/or responsible for transit false positives. We will present the results from searching for companions around over 3,000 Kepler planet hosts in 2012-2015. We will describe our first data release covering 715 planet candidate hosts, and give a preview of ongoing results including improved statistics on the likelihood of false positive planet detections in the Kepler dataset, many new planets in multiple star systems, and new exotic multiple star systems containing Kepler planets.We will also describe the automated Robo-AO survey data reduction methods, including a method of using the large ensemble of target observations as mutual point-spread-function references, along with a new automated companion-detection algorithm designed for extremely large adaptive optics surveys.Our first data release covered 715 objects, searching for companions from 0.15” to 2.5” separation with contrast up to 6 magnitudes. We measured the overall nearby-star-probability for Kepler planet candidates to be 7.4+/-1.0%, and we will detail the variations in this number with stellar host parameters. We will also discuss several KOIs of particular interest, including KOI-191 and KOI-1151, which are both multi-planet systems with detected stellar companions whose unusual planetary system architecture might be best explained if they are ``coincident multiple'' systems, with several transiting planets shared between the two stars. Finally, we will discuss and update the 98%-confidence evidence from our survey that third bodies in star/planet systems produce an excess of close-in giant planets.

  2. Real-time processing for the ATST AO system

    NASA Astrophysics Data System (ADS)

    Richards, K.; Rimmele, T.

    The real-time processing requirements for the four meter Advanced Technology Solar Telescope extended source high order adaptive optics system will be approximately 15 times that of the Dunn Solar Telescope AO systems on which the ATST AO system is based. The ATST AO, with its approximately 1232 subapertures, will use massively parallel processing and is based on Analog Devices TigerSHARC DSPs as the central processing units. We will discuss the requirements for processing and data handling and the architecture of the correlating Shack-Hartmannn and reconstructor processing unit and present the results of bench-mark testing of the DSP hardware that was selected for the ATST AO system.

  3. Inspiratory flow reserve in boys with Duchenne muscular dystrophy.

    PubMed

    De Bruin, P F; Ueki, J; Bush, A; Y Manzur, A; Watson, A; Pride, N B

    2001-06-01

    Patients with advanced muscular dystrophy frequently develop ventilatory failure. Currently respiratory impairment usually is assessed by measuring vital capacity and the mouth pressure generated during a maximal inspiratory maneuver (PI,max), neither of which directly measures ventilatory capacity. We assessed inspiratory flow reserve in 26 boys [mean (SD) age 12.8 (3.8) years] with Duchenne muscular dystrophy (DMD) without ventilatory failure and in 28 normal boys [mean (SD) age 12.6 (1.9) years] by analyzing the ratio between the largest inspiratory flow during tidal breathing (V'I,max(t)) and during a forced vital capacity maneuver (V'I,max(FVC), (V'I,max(t)/V'I,maxFVC). We have compared this ratio with the forced vital capacity FVC and PI,max measured at functional residual capacity. Mean PI,max was -90(30)cmH2O, average 112% (range 57-179%) of predicted values in control boys and -31(11)cmH2O, average 40% predicted values in DMD boys (control vs DMD, P < 0.001). FVC was reduced in DMD boys [59(20)% predicted values vs 86(10)% predicted values in controls, P < 0.01]. Absolute V'I,max(FVC) was strongly related to FVC in both control and DMD boys; V'I,max(FVC) (expressed as FVC. s(-1)) was not related to PI,max in either group. The mean V'I,max(t)/V'I,max(FVC); ratio was higher in DMD 0.22 (0.08) than in controls 0.12 (0.03) (P < 0.001) indicating a reduction in inspiratory flow reserve in DMD. Inspiratory flow reserve was within the normal range in 8 of 19 DMD patients with PI,max less than 50% of predicted values. We conclude that measurement of inspiratory flow reserve (V'I,max(t)/V'I,maxFVC ratio) provides a simple and direct assessment of dynamic inspiratory muscle function which is not replicated by static measurement of PI,max or vital capacity and might be useful in assessment of respiratory impairment in boys with Duchenne muscular dystrophy. Follow-up studies are required to establish whether measures of inspiratory flow reserve are of clinical value

  4. Visible AO Observations at Halpha for Accreting Young Planets

    NASA Astrophysics Data System (ADS)

    Close, L. M.; Follette, K.; Males, J. R.; Morzinski, K.; Rodigas, T. J.; Hinz, P.; Wu, Y.-L.; Apai, D.; Najita, J.; Puglisi, A.; Esposito, S.; Riccardi, A.; Bailey, V.; Xompero, M.; Briguglio, R.; Weinberger, A.

    2014-01-01

    We utilized the new high-order (250-378 mode) Magellan Adaptive Optics system (MagAO) to obtain very high-resolution science in the visible with MagAO's VisAO CCD camera. In the good-median seeing conditions of Magellan (0.5-0.7'') we find MagAO delivers individual short exposure images as good as 19 mas optical resolution. Due to telescope vibrations, long exposure (60s) r' (0.63μm) images are slightly coarser at FWHM = 23-29 mas (Strehl ~ 28%) with bright (R < 9 mag) guide stars. These are the highest resolution filled-aperture images published to date. Images of the young (~ 1 Myr) Orion Trapezium θ1 Ori A, B, and C cluster members were obtained with VisAO. In particular, the 32 mas binary θ1 Ori C 1 C 2 was easily resolved in non-interferometric images for the first time. Relative positions of the bright trapezium binary stars were measured with ~ 0.6-5 mas accuracy. In the second commissioning run we were able to correct 378 modes and achieved good contrasts (Strehl>20% on young transition disks at Hα). We discuss the contrasts achieved at Hα and the possibility of detecting low mass (~ 1-5 Mjup) planets (past 5AU) with our new SAPPHIRES survey with MagAO at Hα.

  5. Bioelectrical Impedance Vector Analysis and Muscular Fitness in Healthy Men

    PubMed Central

    Rodríguez-Rodríguez, Fernando; Cristi-Montero, Carlos; González-Ruíz, Katherine; Correa-Bautista, Jorge Enrique; Ramírez-Vélez, Robinson

    2016-01-01

    Muscle strength can define the general muscular fitness (MF) measurable through hand-grip strength (HG), which is a factor that relates to the health of people of different ages. In this study we evaluated the muscle strength together with a bioimpedance electric analysis in 223 healthy Colombian adult subjects. The bioelectrical impedance vector analysis (BIVA) was conducted to determine the resistance (R), reactance (Xc) and phase angle (PhA). We classified the subjects into three groups (for tertiles), obtaining lower values of R and Xc in subjects with lower HG, plus a high correlation between PhA and HG. An increase in the level of PhA is associated with a high level of MF in a sample of healthy Latin American adult men. The BIVA’s parameters and PhA are a potentially effective preventive measure to be integrated into routine screening in the clinical setting. PMID:27384579

  6. Spinal muscular atrophy: Factors that modulate motor neurone vulnerability.

    PubMed

    Tu, Wen-Yo; Simpson, Julie E; Highley, J Robin; Heath, Paul R

    2017-02-02

    Spinal muscular atrophy (SMA), a leading genetic cause of infant death, is a neurodegenerative disease characterised by the selective loss of particular groups of motor neurones in the anterior horn of the spinal cord with concomitant muscle weakness. To date, no effective treatment is available, however, there are ongoing clinical trials are in place which promise much for the future. However, there remains an ongoing problem in trying to link a single gene loss to motor neurone degeneration. Fortunately, given successful disease models that have been established and intensive studies on SMN functions in the past ten years, we are fast approaching the stage of identifying the underlying mechanisms of SMA pathogenesis Here we discuss potential disease modifying factors on motor neurone vulnerability, in the belief that these factors give insight into the pathological mechanisms of SMA and therefore possible therapeutic targets.

  7. Congenital muscular dystrophy type 1A with residual merosin expression.

    PubMed

    Kim, Hyo Jeong; Choi, Young-Chul; Park, Hyung Jun; Lee, Young-Mock; Kim, Heung Dong; Lee, Joon Soo; Kang, Hoon-Chul

    2014-03-01

    Congenital muscular dystrophy type 1A (MDC1A) is an autosomal recessive disorder characterized by hypotonia, elevated serum creatine kinase level, delayed motor milestones, white matter changes observed by brain magnetic resonance imaging, and normal intelligence. A mutation in the laminin α2 (LAMA2) gene, located at 6q22-23, is a genetic cause of MDC1A. Patients have merosin (laminin α2)-deficient skeletal muscles. However, the degree of merosin expression ranges from total absence to partial reduction. Patients with residual merosin expression have more variable and milder phenotypes than those with absolute merosin deficiency. We observed a Korean girl with MDC1A with residual merosin expression. Clinical presentation of this patient was typical except for late onset of the disease and external capsule involvement. Immunohistochemical staining of muscle fibers including merosin, is important to evaluate patients with hypotonia, delayed motor development, and abnormal white matter changes.

  8. Human X chromosome markers and Duchenne muscular dystrophy.

    PubMed Central

    Davies, K E; Speer, A; Herrmann, F; Spiegler, A W; McGlade, S; Hofker, M H; Briand, P; Hanke, R; Schwartz, M; Steinbicker, V

    1985-01-01

    Two DNA markers, a random DNA fragment 754 and the cDNA sequence encoding the gene for ornithine transcarbamylase (OTC) have been studied in kindreds segregating for Duchenne muscular dystrophy. 754 and OTC are located close physically to the mutation in the region Xp21 below the breakpoints in two Duchenne females. The genetic distance was found to be approximately 10cM between 754 and DMD (two crossovers in 26 meioses) and to be approximately 10cM between OTC and DMD (two crossovers in 26 meioses). Physical data suggest the order DMD-754-OTC. The frequency of recombination compared to physical distance between these markers and DMD suggests that there may be a hot spot of recombination. The relevance of these observations for the isolation of the DMD mutation and clinical use of these probes is discussed. Images PMID:3859837

  9. Laminins in peripheral nerve development and muscular dystrophy.

    PubMed

    Yu, Wei-Ming; Yu, Huaxu; Chen, Zu-Lin

    2007-06-01

    Laminins are extracellular matrix (ECM) proteins that play an important role in cellular function and tissue morphogenesis. In the peripheral nervous system (PNS), laminins are expressed in Schwann cells and participate in their development. Mutations in laminin subunits expressed in the PNS and in skeleton muscle may cause peripheral neuropathies and muscular dystrophy in both humans and mice. Recent studies using gene knockout technology, such as cell-type specific gene targeting techniques, revealed that laminins and their receptors mediate Schwann cell and axon interactions. Schwann cells with disrupted laminin expression exhibit impaired proliferation and differentiation and also undergo apoptosis. In this review, we focus on the potential molecular mechanisms by which laminins participate in the development of Schwann cells.

  10. Genome Editing Gene Therapy for Duchenne Muscular Dystrophy.

    PubMed

    Hotta, Akitsu

    2015-09-22

    Duchenne muscular dystrophy (DMD) is a severe genetic disorder caused by loss of function of the dystrophin gene on the X chromosome. Gene augmentation of dystrophin is challenging due to the large size of the dystrophin cDNA. Emerging genome editing technologies, such as TALEN and CRISPR-Cas9 systems, open a new erain the restoration of functional dystrophin and are a hallmark of bona fide gene therapy. In this review, we summarize current genome editing approaches, properties of target cell types for ex vivo gene therapy, and perspectives of in vivo gene therapy including genome editing in human zygotes. Although technical challenges, such as efficacy, accuracy, and delivery of the genome editing components, remain to be further improved, yet genome editing technologies offer a new avenue for the gene therapy of DMD.

  11. [Development of therapeutics for spinal and bulbar muscular atrophy (SBMA)].

    PubMed

    Sobue, Gen

    2003-11-01

    Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a hereditary motor neuron disease that affects males, caused by the expansion of a polyglutamine (polyQ) tract in androgen receptor (AR). Female carriers are usually asymptomatic. The transgenic mouse (Tg) model carrying a full-length human AR with expanded polyQ has significant gender-related motor impairment. This phenotype is inhibited by castration, which prevents nuclear translocation of mutant AR. Leuprorelin, an LHRH agonist that reduces testosterone release from the testis, also rescues motor dysfunction and nuclear accumulation of mutant AR in the male Tg. Over-expression of a molecular chaperone HSP70, which renatures misfolded mutant AR, ameliorates neuromuscular phenotypes of the Tg by reducing nuclear-localized mutant AR. HSP70 appears to enhance the degradation of mutant AR via ubiquitin-proteasome pathway. These experimental approaches indicate the possibility of clinical application of drugs, such as leuprorelin, for SBMA patients.

  12. RASCH ANALYSIS OF CLINICAL OUTCOME MEASURES IN SPINAL MUSCULAR ATROPHY

    PubMed Central

    CANO, STEFAN J.; MAYHEW, ANNA; GLANZMAN, ALLAN M.; KROSSCHELL, KRISTIN J.; SWOBODA, KATHRYN J.; MAIN, MARION; STEFFENSEN, BIRGIT F.; BÉRARD, CAROLE; GIRARDOT, FRANÇOISE; PAYAN, CHRISTINE A.M.; MERCURI, EUGENIO; MAZZONE, ELENA; ELSHEIKH, BAKRI; FLORENCE, JULAINE; HYNAN, LINDA S.; IANNACCONE, SUSAN T.; NELSON, LESLIE L.; PANDYA, SHREE; ROSE, MICHAEL; SCOTT, CHARLES; SADJADI, REZA; YORE, MACKENSIE A.; JOYCE, CYNTHIA; KISSEL, JOHN T.

    2015-01-01

    Introduction Trial design for SMA depends on meaningful rating scales to assess outcomes. In this study Rasch methodology was applied to 9 motor scales in spinal muscular atrophy (SMA). Methods Data from all 3 SMA types were provided by research groups for 9 commonly used scales. Rasch methodology assessed the ordering of response option thresholds, tests of fit, spread of item locations, residual correlations, and person separation index. Results Each scale had good reliability. However, several issues impacting scale validity were identified, including the extent that items defined clinically meaningful constructs and how well each scale measured performance across the SMA spectrum. Conclusions The sensitivity and potential utility of each SMA scale as outcome measures for trials could be improved by establishing clear definitions of what is measured, reconsidering items that misfit and items whose response categories have reversed thresholds, and adding new items at the extremes of scale ranges. PMID:23836324

  13. Descriptive epidemiology of spinal muscular atrophy type I in Estonia.

    PubMed

    Vaidla, Eve; Talvik, Inga; Kulla, Andres; Kahre, Tiina; Hamarik, Malle; Napa, Aita; Metsvaht, Tuuli; Piirsoo, Andres; Talvik, Tiina

    2006-01-01

    Spinal muscular atrophy is the second most frequent autosomal-recessive disorder in Europeans. There are no published epidemiological data on SMA in Estonia and other Baltic countries. The aim of this study was to estimate the incidence of SMA I in Estonia. All patients with SMA I diagnosed between January 1994 and December 2003 were included in the study. The diagnosis was established on the basis of neurological evaluation, ENMG findings, molecular studies and muscle biopsy. PCR and restriction enzyme analysis was used to detect the homozygous deletion of the SMN1 gene. A total of 9 cases of SMA I were identified during this 10-year period. The incidence of SMA I in Estonia is 1 in 14,400 live births, which is similar to the result from Hungary but lower than average incidence in the world. Only one of the patients was female. Typical SMN1 gene deletion was found in all cases.

  14. Dropped-head in recessive oculopharyngeal muscular dystrophy.

    PubMed

    Garibaldi, Matteo; Pennisi, Elena Maria; Bruttini, Mirella; Bizzarri, Veronica; Bucci, Elisabetta; Morino, Stefania; Talerico, Caterina; Stoppacciaro, Antonella; Renieri, Alessandra; Antonini, Giovanni

    2015-11-01

    A 69-year-old woman presented a dropped head, caused by severe neck extensor weakness that had started two years before. She had also developed a mild degree of dysphagia, rhinolalia, eyelid ptosis and proximal limb weakness during the last months. EMG revealed myopathic changes. Muscle MRI detected fatty infiltration in the posterior neck muscles and tongue. Muscle biopsy revealed fiber size variations, sporadic rimmed vacuoles, small scattered angulated fibers and a patchy myofibrillar network. Genetic analysis revealed homozygous (GCN)11 expansions in the PABPN1 gene that were consistent with recessive oculopharyngeal muscular dystrophy (OPMD). There are a few reports of the recessive form, which has a later disease onset with milder symptoms and higher clinical variability than the typical dominantly inherited form. This patient, who is the first Italian and the eighth worldwide reported case of recessive OPMD, is also the first case of OPMD with dropped-head syndrome, which thus expands the clinical phenotype of recessive OPMD.

  15. Whole-body MRI evaluation of facioscapulohumeral muscular dystrophy

    PubMed Central

    Leung, Doris G.; Carrino, John A.; Wagner, Kathryn R.; Jacobs, Michael A.

    2015-01-01

    Introduction Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary disorder that causes progressive muscle wasting. Increasing knowledge of the pathophysiology of FSHD has stimulated interest in developing biomarkers of disease severity. Methods Two groups of MRI scans were analyzed: whole-body scans from 13 subjects with FSHD, and upper and lower extremity scans from 34 subjects with FSHD who participated in the MYO-029 clinical trial. Muscles were scored for fat infiltration and edema-like changes. Fat infiltration scores were compared to muscle strength and function. Results Our analysis reveals a distinctive pattern of both frequent muscle involvement and frequent sparing in FSHD. Averaged fat infiltration scores for muscle groups in the legs correlated with quantitative muscle strength and 10-meter walk times. Discussion Advances in MRI technology allow for the acquisition of rapid, high-quality whole-body imaging in diffuse muscle disease. This technique offers a promising disease biomarker in FSHD and other muscle diseases. PMID:25641525

  16. Drug Discovery of Therapies for Duchenne Muscular Dystrophy.

    PubMed

    Blat, Yuval; Blat, Shachar

    2015-12-01

    Duchenne muscular dystrophy (DMD) is a genetic, lethal, muscle disorder caused by the loss of the muscle protein, dystrophin, leading to progressive loss of muscle fibers and muscle weakness. Drug discovery efforts targeting DMD have used two main approaches: (1) the restoration of dystrophin expression or the expression of a compensatory protein, and (2) the mitigation of downstream pathological mechanisms, including dysregulated calcium homeostasis, oxidative stress, inflammation, fibrosis, and muscle ischemia. The aim of this review is to introduce the disease, its pathophysiology, and the available research tools to a drug discovery audience. This review will also detail the most promising therapies that are currently being tested in clinical trials or in advanced preclinical models.

  17. [Potential of the zebrafish model to study congenital muscular dystrophies].

    PubMed

    Ryckebüsch, Lucile

    2015-10-01

    In order to better understand the complexity of congenital muscular dystrophies (CMD) and develop new strategies to cure them, it is important to establish new disease models. Due to its numerous helpful attributes, the zebrafish has recently become a very powerful animal model for the study of CMD. For some CMD, this vertebrate model is phenotypically closer to human pathology than the murine model. Over the last few years, researchers have developed innovative techniques to screen rapidly and on a large scale for muscle defects in zebrafish. Furthermore, new genome editing techniques in zebrafish make possible the identification of new disease models. In this review, the major attributes of zebrafish for CMD studies are discussed and the principal models of CMD in zebrafish are highlighted.

  18. Duchenne muscular dystrophy drugs face tough path to approval.

    PubMed

    Hodgkinson, L; Sorbera, L; Graul, A I

    2016-03-01

    Highly anticipated as new disease-modifying treatments for Duchenne muscular dystrophy (DMD), therapeutics by BioMarin Pharmaceutical (Kyndrisa™; drisapersen) and Sarepta Therapeutics (eteplirsen; AVI-4658) both recently received negative FDA reviews and are now facing battles for approval in the U.S. At present, BioMarin is committed to working with the FDA to forge a pathway to approval following the failure of its NDA, while Sarepta awaits the formal decision on its NDA, which is expected by late May 2016. Despite the critical nature of both reviews, analysts consider that there is still a narrow possibility of approval of both drugs. According to Consensus forecasts from Thomson Reuters Cortellis for Competitive Intelligence, Kyndrisa is forecast to achieve sales of USD 533.71 million in 2021.

  19. Study of muscular deformation based on surface slope estimation

    NASA Astrophysics Data System (ADS)

    Carli, M.; Goffredo, M.; Schmid, M.; Neri, A.

    2006-02-01

    During contraction and stretching, muscles change shape and size, and produce a deformation of skin tissues and a modification of the body segment shape. In human motion analysis, it is very important to take into account these phenomena. The aim of this work is the evaluation of skin and muscular deformation, and the modeling of body segment elastic behavior obtained by analysing video sequences that capture a muscle contraction. The soft tissue modeling is accomplished by using triangular meshes that automatically adapt to the body segment during the execution of a static muscle contraction. The adaptive triangular mesh is built on reference points whose motion is estimated by using non linear operators. Experimental results, obtained by applying the proposed method to several video sequences, where biceps brachial isometric contraction was present, show the effectiveness of this technique.

  20. Independent Association of Muscular Strength and Carotid Intima-Media Thickness in Children.

    PubMed

    Melo, X; Santa-Clara, H; Santos, D A; Pimenta, N M; Minderico, C S; Fernhall, B; Sardinha, L B

    2015-07-01

    The aim of this cross-sectional study was to examine the influence of muscular strength on carotid intima-media thickness (cIMT) in children, controlling for the effect of cardiorespiratory fitness (CRF) and central adiposity and to examine if differences among muscular strength tertiles translate to physiological differences. We assessed cIMT of the common carotid artery in 366 children between 11-12 years of age (191 girls). Measures included cIMT assessed with high-resolution ultrasonography, a maximal handgrip strength test, body fat mass and lean mass from DXA and CRF determined using a maximal cycle ergometer test. Association between muscular strength and cIMT adjusted for CRF and central adiposity, as measured by trunk fat, was tested with multiple linear regression analysis. Differences in risk factors among muscular strength groups were tested with ANOVA. The Muscular Strength Index (MSI) was inversely associated with cIMT independently of CRF and central adiposity (p<0.05). The low MSI group had the highest values of cIMT, waist circumference and systolic blood pressure and the lowest CRF (p<0.05). There was an inverse and independent association between muscular strength and cIMT. Low muscular strength was associated with higher levels of cardiovascular disease risk factors in children.

  1. Drive for muscularity and social physique anxiety mediate the perceived ideal physique muscle dysmorphia relationship.

    PubMed

    Thomas, Adam; Tod, David A; Edwards, Christian J; McGuigan, Michael R

    2014-12-01

    This study examined the mediating role of drive for muscularity and social physique anxiety (SPA) in the perceived muscular male ideal physique and muscle dysmorphia relationship in weight training men. Men (N = 146, mean ± SD; age, 22.8 ± 5.0 years; weight, 82.0 ± 11.1 kg; height, 1.80 ± 0.07 m; body mass index, 25.1 ± 3.0) who participated in weight training completed validated questionnaires measuring drive for muscularity, SPA, perceived muscular male ideal physique, global muscle dysmorphia, and several characteristics of muscle dysmorphia (exercise dependence, diet manipulation, concerns about size/symmetry, physique protection behavior, and supplementation). Perceived ideal physique was an independent predictor of muscle dysmorphia measures except physique protection (coefficients = 0.113-0.149, p ≤ 0.05). Perceived ideal physique also predicted muscle dysmorphia characteristics (except physique protection and diet) through the indirect drive for muscularity pathway (coefficients = 0.055-0.116, p ≤ 0.05). Perceived ideal physique also predicted size/symmetry concerns and physique protection through the indirect drive for muscularity and SPA pathway (coefficients = 0.080-0.025, p ≤ 0.05). These results extend current research by providing insights into the way correlates of muscle dysmorphia interact to predict the condition. The results also highlight signs (e.g., anxiety about muscularity) that strength and conditioning coaches can use to identify at-risk people who may benefit from being referred for psychological assistance.

  2. [Genetic Diagnosis and Molecular Therapies for Duchenne Muscular Dystrophy].

    PubMed

    Takeshima, Yasuhiro

    2015-10-01

    Duchenne muscular dystrophy (DMD) is the most common form of inherited muscle disease and is characterized by progressive muscle wasting, ultimately resulting in the death of patients in their twenties or thirties. DMD is characterized by a deficiency of the muscle dystrophin as a result of mutations in the dystrophin gene. Currently, no effective treatment for DMD is available. Promising molecular therapies which are mutation-specific have been developed. Transformation of an out-of-frame mRNA into an in-frame dystrophin message by inducing exon skipping is considered one of the approaches most likely to lead to success. We demonstrated that the intravenous administration of the antisense oligonucleotide against the splicing enhancer sequence results in exon skipping and production of the dystrophin protein in DMD case for the first time. After extensive studies, anti-sense oligonucleotides comprising different monomers have undergone clinical trials and provided favorable results, enabling improvements in ambulation of DMD patients. Induction of the read-through of nonsense mutations is expected to produce dystrophin in DMD patients with nonsense mutations, which are detected in 19% of DMD cases. The clinical effectiveness of gentamicin and PTC124 has been reported. We have demonstrated that arbekacin-mediated read-through can markedly ameliorate muscular dystrophy in vitro. We have already begun a clinical trial of nonsense mutation read-through therapy using arbekacin. Some of these drug candidates are planned to undergo submission for approval to regulatory agencies in the US and EU. We hope that these molecular therapies will contribute towards DMD treatment.

  3. Tadalafil alleviates muscle ischemia in patients with Becker muscular dystrophy.

    PubMed

    Martin, Elizabeth A; Barresi, Rita; Byrne, Barry J; Tsimerinov, Evgeny I; Scott, Bryan L; Walker, Ashley E; Gurudevan, Swaminatha V; Anene, Francine; Elashoff, Robert M; Thomas, Gail D; Victor, Ronald G

    2012-11-28

    Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease for which there is no treatment. Like Duchenne muscular dystrophy (DMD), BMD is caused by mutations in the gene encoding dystrophin, a structural cytoskeletal protein that also targets other proteins to the muscle sarcolemma. Among these is neuronal nitric oxide synthase (nNOSμ), which requires certain spectrin-like repeats in dystrophin's rod domain and the adaptor protein α-syntrophin to be targeted to the sarcolemma. When healthy skeletal muscle is subjected to exercise, sarcolemmal nNOSμ-derived NO attenuates local α-adrenergic vasoconstriction, thereby optimizing perfusion of muscle. We found previously that this protective mechanism is defective-causing functional muscle ischemia-in dystrophin-deficient muscles of the mdx mouse (a model of DMD) and of children with DMD, in whom nNOSμ is mislocalized to the cytosol instead of the sarcolemma. We report that this protective mechanism also is defective in men with BMD in whom the most common dystrophin mutations disrupt sarcolemmal targeting of nNOSμ. In these men, the vasoconstrictor response, measured as a decrease in muscle oxygenation, to reflex sympathetic activation is not appropriately attenuated during exercise of the dystrophic muscles. In a randomized placebo-controlled crossover trial, we show that functional muscle ischemia is alleviated and normal blood flow regulation is fully restored in the muscles of men with BMD by boosting NO-cGMP (guanosine 3',5'-monophosphate) signaling with a single dose of the drug tadalafil, a phosphodiesterase 5A inhibitor. These results further support an essential role for sarcolemmal nNOSμ in the normal modulation of sympathetic vasoconstriction in exercising human skeletal muscle and implicate the NO-cGMP pathway as a putative new target for treating BMD.

  4. Current and emerging treatment strategies for Duchenne muscular dystrophy

    PubMed Central

    Mah, Jean K

    2016-01-01

    Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood. It is caused by mutations of the DMD gene, leading to progressive muscle weakness, loss of independent ambulation by early teens, and premature death due to cardiorespiratory complications. The diagnosis can usually be made after careful review of the history and examination of affected boys presenting with developmental delay, proximal weakness, and elevated serum creatine kinase, plus confirmation by muscle biopsy or genetic testing. Precise characterization of the DMD mutation is important for genetic counseling and individualized treatment. Current standard of care includes the use of corticosteroids to prolong ambulation and to delay the onset of secondary complications. Early use of cardioprotective agents, noninvasive positive pressure ventilation, and other supportive strategies has improved the life expectancy and health-related quality of life for many young adults with DMD. New emerging treatment includes viral-mediated microdystrophin gene replacement, exon skipping to restore the reading frame, and nonsense suppression therapy to allow translation and production of a modified dystrophin protein. Other potential therapeutic targets involve upregulation of compensatory proteins, reduction of the inflammatory cascade, and enhancement of muscle regeneration. So far, data from DMD clinical trials have shown limited success in delaying disease progression; unforeseen obstacles included immune response against the generated mini-dystrophin, inconsistent evidence of dystrophin production in muscle biopsies, and failure to demonstrate a significant improvement in the primary outcome measure, as defined by the 6-minute walk test in some studies. The long-term safety and efficacy of emerging treatments will depend on the selection of appropriate clinical end points and sensitive biomarkers to detect meaningful changes in disease progression. Correction of the underlying

  5. Muscular strength profile in Tunisian male national judo team

    PubMed Central

    Ghrairi, Mourad; Hammouda, Omar; Malliaropoulos, Nikos

    2014-01-01

    Summary Background: it is well established that muscle strength is a determinant factor in judo. However, little data are available for African athletes. Therefore, the aim of this study was to provide reference data of the muscular strength profile (MSP) for an African team, Tunisian judo team. Methods: the study was conducted among ten international judo athletes from Tunisia. To determine their MSP, we used an isokinetic dynamometer to assess Hamstrings, Quadriceps of both knees and external, internal rotators of both shoulders. The angular velocities of the assessments were; 90, 180, 240°/s for the knees and 60, 120°/s for the shoulders. Results: MSP was determined based on two parameters; the maximum peak torque (PT) of each muscle and the ratio agonistic/antagonistic muscles (R). The knee extensors and flexors in the “supporting leg” had higher PT than in the “attacking leg”; respectively, 245N.m versus 237 (p<0.05) and 147 N.m versus 145 (p>0.05). R was normal for both legs. Furthermore, both rotators of the dominant shoulder had higher PT; 84 N.m versus 71 for the internal rotators (p<0.05) and 34,7 N.m versus 29,0 for the lateral rotators (p<0.05). Inversely, R was higher in the non-dominant side; 45% versus 35, p<0.05). Conclusion: the MSP of the selected elites Tunisian judo athletes was characterized by 3 major features; a strength of the quadriceps in the standing leg significantly higher than in the attacking leg, a normal muscular balance Hamstrings/quadriceps in both legs and a strength of the shoulder’ rotators higher in the dominant side. PMID:25332926

  6. Motor unit reorganization in progressive muscular dystrophies and congenital myopathies.

    PubMed

    Szmidt-Sałkowska, Elżbieta; Gaweł, Małgorzata; Lipowska, Marta

    2015-01-01

    The aim of this study was to analyze motor unit reorganization in different types of progressive muscular dystrophies and congenital myopathies. The study population consisted of patients with genetically verified progressive muscular dystrophies: Duchenne (DMD) (n=54), Becker (BMD) (n=30), facio-scapulo-humeral (FSHD) (n=37), and Emery-Dreifuss (E-DD) (n=26). Patients with probable limb-girdle dystrophy (L-GD) (n=58) and congenital myopathies (n=35) were also included in the study. Quantitative EMG recordings were obtained from 469 muscles. Muscle activity at rest and during slight voluntary and maximal muscle contraction was analyzed. The motor unit activity potential (MUAP) duration, amplitude, area, size index (SI), polyphasicity, and the presence of "outliers" were evaluated. Diminished values of MUAP parameters and decreased maximal amplitude of maximal muscle contraction were recorded most frequently in DMD and mainly in the biceps brachii muscles. SI was the most frequently changed EMG parameter. "Outliers" with amplitude below the normal range were recorded more frequently then a decreased mean MUAP amplitude (what could indicate a very high sensitivity of this EMG parameter). Pathological interference pattern was recorded in 34.7% of biceps brachii and in 21.2% of rectus femoris muscles. In FSHD, decreased MUAP duration and SI and pathological interference pattern with low amplitude were recorded most frequently in the tibial anterior and deltoid muscles. The presence of potentials with reduced parameters is a result of decreasing motor unit area (reduced number and size of muscle fibers), while high amplitude potentials recorded in BMD and E-DD could indicate a slow and mild course of disease and muscle regeneration.

  7. [The ultrasound assessment of neuro-muscular apparatus by the radial nerve injuries].

    PubMed

    Golubev, V G; Kkhir Bek, M; Iulov, V V; Goncharov, N G

    2011-01-01

    The use of ultrasound (US) scanning to assess the muscular function during the reinnervation is a new concept in medicine. The US signs of muscle denervation were thoroughly described in the article. The US muscle monitoring was performed by the complete and partial radial nerve injury in various follow-up periods. Absolute and relative indications for surgery were determined. The comparative characteristics of structural muscular changes, together with the US test for the assessment of the treatment efficacy and nerval and muscular recovery were suggested.

  8. Neuroblastoma in a Patient With Spinal Muscular Atrophy Type I: Is It Just a Coincidence?

    PubMed

    Sag, Erdal; Sen, Hilal Susam; Haliloglu, Goknur; Yalcin, Bilgehan; Kutluk, Tezer

    2015-07-01

    Spinal muscular atrophy is an autosomal recessive disorder characterized by progressive degeneration of anterior horn cells of the spinal cord resulting in hypotonia, skeletal muscle atrophy, and weakness. Herein, we report a 4-month-old male infant who presented to our hospital with an abdominal mass that was diagnosed as neuroblastoma and spinal muscular atrophy type I. We would like to discuss the course and differential diagnosis with an algorithm leading to the diagnosis in this peculiar patient. To our knowledge, coexistence of spinal muscular atrophy type I and neuroblastoma is defined for the first time in the literature.

  9. The Intriguing Regulators of Muscle Mass in Sarcopenia and Muscular Dystrophy

    PubMed Central

    Sakuma, Kunihiro; Aoi, Wataru; Yamaguchi, Akihiko

    2014-01-01

    Recent advances in our understanding of the biology of muscle have led to new interest in the pharmacological treatment of muscle wasting. Loss of muscle mass and increased intramuscular fibrosis occur in both sarcopenia and muscular dystrophy. Several regulators (mammalian target of rapamycin, serum response factor, atrogin-1, myostatin, etc.) seem to modulate protein synthesis and degradation or transcription of muscle-specific genes during both sarcopenia and muscular dystrophy. This review provides an overview of the adaptive changes in several regulators of muscle mass in both sarcopenia and muscular dystrophy. PMID:25221510

  10. A ubiquitous wearable unit for controlling muscular fatigue during cycling exercise sessions.

    PubMed

    Kiryu, Tohru; Yamashita, Kazuki

    2007-01-01

    For health promotion and motor rehabilitation, controlling muscular fatigue on-site is important during exercise sessions. We have developed a ubiquitous wearable unit with a Linux board and tried to apply it to the control of a torque-assisted bicycle with a biosignal-based fuzzy system designed for a cycle ergometer. The results showed that an appropriate design for the cycle ergometor (indoor exercise) would be sufficiently applicable for the torque-assisted bicycle (outdoor exercise) in terms of heart rate, but was not sufficient in terms of muscular fatigue. It needs more detailed control for muscular activity.

  11. Serum profiling identifies novel muscle miRNA and cardiomyopathy-related miRNA biomarkers in Golden Retriever muscular dystrophy dogs and Duchenne muscular dystrophy patients.

    PubMed

    Jeanson-Leh, Laurence; Lameth, Julie; Krimi, Soraya; Buisset, Julien; Amor, Fatima; Le Guiner, Caroline; Barthélémy, Inès; Servais, Laurent; Blot, Stéphane; Voit, Thomas; Israeli, David

    2014-11-01

    Duchenne muscular dystrophy (DMD) is a fatal, X-linked neuromuscular disease that affects 1 boy in 3500 to 5000 boys. The golden retriever muscular dystrophy dog is the best clinically relevant DMD animal model. Here, we used a high-thoughput miRNA sequencing screening for identification of candidate serum miRNA biomarkers in golden retriever muscular dystrophy dogs. We confirmed the dysregulation of the previously described muscle miRNAs, miR-1, miR-133, miR-206, and miR-378, and identified a new candidate muscle miRNA, miR-95. We identified two other classes of dysregulated serum miRNAs in muscular dystrophy: miRNAs belonging to the largest known miRNA cluster that resides in the imprinting DLK1-DIO3 genomic region and miRNAs associated with cardiac disease, including miR-208a, miR-208b, and miR-499. No simple correlation was identified between serum levels of cardiac miRNAs and cardiac functional parameters in golden retriever muscular dystrophy dogs. Finally, we confirmed a dysregulation of miR-95, miR-208a, miR-208b, miR-499, and miR-539 in a small cohort of DMD patients. Given the interspecies conservation of miRNAs and preliminary data in DMD patients, these newly identified dysregulated miRNAs are strong candidate biomarkers for DMD patients.

  12. Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet): case definition in surveillance for childhood-onset Duchenne/Becker muscular dystrophy.

    PubMed

    Mathews, Katherine D; Cunniff, Chris; Kantamneni, Jiji R; Ciafaloni, Emma; Miller, Timothy; Matthews, Dennis; Cwik, Valerie; Druschel, Charlotte; Miller, Lisa; Meaney, F John; Sladky, John; Romitti, Paul A

    2010-09-01

    The Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) is a multisite collaboration to determine the prevalence of childhood-onset Duchenne/Becker muscular dystrophy and to characterize health care and health outcomes in this population. MD STARnet uses medical record abstraction to identify patients with Duchenne/Becker muscular dystrophy born January 1, 1982 or later who resided in 1 of the participating sites. Critical diagnostic elements of each abstracted record are reviewed independently by >4 clinicians and assigned to 1 of 6 case definition categories (definite, probable, possible, asymptomatic, female, not Duchenne/Becker muscular dystrophy) by consensus. As of November 2009, 815 potential cases were reviewed. Of the cases included in analysis, 674 (82%) were either ''definite'' or ''probable'' Duchenne/Becker muscular dystrophy. These data reflect a change in diagnostic testing, as case assignment based on genetic testing increased from 67% in the oldest cohort (born 1982-1987) to 94% in the cohort born 2004 to 2009.

  13. Beyond the Blur: Construction and Characterization of the First Autonomous AO System, and, An AO Survey of Magnetar Proper Motions

    NASA Astrophysics Data System (ADS)

    Tendulkar, Shriharsh Prakash

    Adaptive optics (AO) corrects distortions created by atmospheric turbulence and delivers diffraction-limited images on ground-based telescopes. The vastly improved spatial resolution and sensitivity has been utilized for studying everything from the magnetic fields of sunspots upto the internal dynamics of high-redshift galaxies. This thesis about AO science from small and large telescopes is divided into two parts: Robo-AO and magnetar kinematics. In the first part, I discuss the construction and performance of the world's first fully autonomous visible light AO system, Robo-AO, at the Palomar 60-inch telescope. Robo-AO operates extremely efficiently with an overhead < 50s, typically observing about 22 targets every hour. We have performed large AO programs observing a total of over 7,500 targets since May 2012. In the visible band, the images have a Strehl ratio of about 10% and achieve a contrast of upto 6 magnitudes at a separation of 1‧‧. The full-width at half maximum achieved is 110-130 milli-arcsecond. I describe how Robo-AO is used to constrain the evolutionary models of low-mass pre-main-sequence stars by measuring resolved spectral energy distributions of stellar multiples in the visible band, more than doubling the current sample. I conclude this part with a discussion of possible future improvements to the Robo-AO system. In the second part, I describe a study of magnetar kinematics using high-resolution near-infrared (NIR) AO imaging from the 10-meter Keck II telescope. Measuring the proper motions of five magnetars with a precision of upto 0.7 milli-arcsecond/yr -1, we have more than tripled the previously known sample of magnetar proper motions and proved that magnetar kinematics are equivalent to those of radio pulsars. We conclusively showed that SGR 1900+14 and SGR 1806-20 were ejected from the stellar clusters with which they were traditionally associated. The inferred kinematic ages of these two magnetars are 6 +/- 1.8 kyr and 650 +/-3 00

  14. Characterizing and mitigating vibrations for SCExAO

    NASA Astrophysics Data System (ADS)

    Lozi, Julien; Guyon, Olivier; Jovanovic, Nemanja; Singh, Garima; Goebel, Sean; Norris, Barnaby; Okita, Hirofumi

    2016-07-01

    The Subaru Coronagraphic Extreme Adaptive Optics (SCExAO) instrument, under development for the Subaru Telescope, has currently the fastest on-sky wavefront control loop, with a pyramid wavefront sensor running at 3.5 kHz. But even at that speed, we are still limited by low-frequency vibrations. The current main limitation was found to be vibrations attributed mainly to the rotation of the telescope. Using the fast wavefront sensors, cameras and accelerometers, we managed to identify the origin of most of the vibrations degrading our performance. Low-frequency vibrations are coming from the telescope drive in azimuth and elevation, as well as the elevation encoders when the target is at transit. Other vibrations were found at higher frequency coming from the image rotator inside Subaru's adaptive optics facility AO188. Different approaches are being implemented to take care of these issues. The PID control of the image rotator has been tuned to reduce their high-frequency contribution. We are working with the telescope team to tune the motor drives and reduce the impact of the elevation encoder. A Linear Quadratic Gaussian controller (LQG, or Kalman filter) is also being implemented inside SCExAO to control these vibrations. These solutions will not only improve significantly SCExAOs performance, but will also help all the other instruments on the Subaru Telescope, especially the ones behind AO188. Ultimately, this study will also help the development of the TMT, as these two telescopes share very similar drives.

  15. Antisense Oligonucleotides Used to Target the DUX4 mRNA as Therapeutic Approaches in FaciosScapuloHumeral Muscular Dystrophy (FSHD)

    PubMed Central

    Ansseau, Eugénie; Vanderplanck, Céline; Wauters, Armelle; Harper, Scott Q.; Coppée, Frédérique; Belayew, Alexandra

    2017-01-01

    FacioScapuloHumeral muscular Dystrophy (FSHD) is one of the most prevalent hereditary myopathies and is generally characterized by progressive muscle atrophy affecting the face, scapular fixators; upper arms and distal lower legs. The FSHD locus maps to a macrosatellite D4Z4 repeat array on chromosome 4q35. Each D4Z4 unit contains a DUX4 gene; the most distal of which is flanked by a polyadenylation site on FSHD-permissive alleles, which allows for production of stable DUX4 mRNAs. In addition, an open chromatin structure is required for DUX4 gene transcription. FSHD thus results from a gain of function of the toxic DUX4 protein that normally is only expressed in germ line and stem cells. Therapeutic strategies are emerging that aim to decrease DUX4 expression or toxicity in FSHD muscle cells. We review here the heterogeneity of DUX4 mRNAs observed in muscle and stem cells; and the use of antisense oligonucleotides (AOs) targeting the DUX4 mRNA to interfere either with transcript cleavage/polyadenylation or intron splicing. We show in primary cultures that DUX4-targeted AOs suppress the atrophic FSHD myotube phenotype; but do not improve the disorganized FSHD myotube phenotype which could be caused by DUX4c over-expression. Thus; DUX4c might constitute another therapeutic target in FSHD. PMID:28273791

  16. Antisense Oligonucleotides Used to Target the DUX4 mRNA as Therapeutic Approaches in FaciosScapuloHumeral Muscular Dystrophy (FSHD).

    PubMed

    Ansseau, Eugénie; Vanderplanck, Céline; Wauters, Armelle; Harper, Scott Q; Coppée, Frédérique; Belayew, Alexandra

    2017-03-03

    FacioScapuloHumeral muscular Dystrophy (FSHD) is one of the most prevalent hereditary myopathies and is generally characterized by progressive muscle atrophy affecting the face, scapular fixators; upper arms and distal lower legs. The FSHD locus maps to a macrosatellite D4Z4 repeat array on chromosome 4q35. Each D4Z4 unit contains a DUX4 gene; the most distal of which is flanked by a polyadenylation site on FSHD-permissive alleles, which allows for production of stable DUX4 mRNAs. In addition, an open chromatin structure is required for DUX4 gene transcription. FSHD thus results from a gain of function of the toxic DUX4 protein that normally is only expressed in germ line and stem cells. Therapeutic strategies are emerging that aim to decrease DUX4 expression or toxicity in FSHD muscle cells. We review here the heterogeneity of DUX4 mRNAs observed in muscle and stem cells; and the use of antisense oligonucleotides (AOs) targeting the DUX4 mRNA to interfere either with transcript cleavage/polyadenylation or intron splicing. We show in primary cultures that DUX4-targeted AOs suppress the atrophic FSHD myotube phenotype; but do not improve the disorganized FSHD myotube phenotype which could be caused by DUX4c over-expression. Thus; DUX4c might constitute another therapeutic target in FSHD.

  17. Columbia SMA Project: A Randomized, Control Trial of the Effects of Exercise on Motor Function and Strength in Patients With Spinal Muscular Atrophy (SMA)

    DTIC Science & Technology

    2011-06-01

    www.CQillmbiasma.org No. 1994 ?. 2 Musc::ular Dystrophy Assoc1at1on (hUAJ Clinic Spinal Muscular Atrophy Clinical (SMA) Research Center Nan<:y E. Strauss, M.D...3 ~ COLUMBIA UNIVERSIT~ 0 ~ Muscutar Dystrophy Association (MDA) Clinic \\WI M C Spinal Muscular Atrophy Clinical {SMA) - EDICAL ENTER Research...9lu mbi~_rlli:’U~t9 0000000000 p.1 Muscular Dystrophy Association (MDA) Clinic Spinal Muscular Atrophy Clinical (SMA) Research Center Nancy E

  18. Predicting muscularity-related behavior, emotions, and cognitions in men: The role of psychological need thwarting, drive for muscularity, and mesomorphic internalization.

    PubMed

    Edwards, Christian; Tod, David; Molnar, Gyozo; Markland, David

    2016-09-01

    We examine the relationships that internalization, need thwarting (NT), and drive for muscularity (DFM), along with their interactions, had with weightlifting, muscle dissatisfaction (MD), and muscle-related-worry (MRW). A sample of 552 men (MAge=20.5 years, SD=3.1) completed the Psychological Need Thwarting Scale, the Internalization subscale of the male version of the Sociocultural Attitudes Towards Appearance Questionnaire, the Drive for Muscularity Scale-Attitudes subscale, the Male Body Attitudes Scale-Muscularity subscale, the Body Change Inventory-Worry subscale, and an inventory assessing weightlifting behavior. DFM significantly predicted weightlifting, MRW, and MD. Internalization significantly predicted weightlifting and MRW. NT significantly predicted weightlifting and MD, and its relationship with MRW approached significance. The interaction terms did not predict weightlifting or MRW. The NT/DFM and NT/Internalization interaction terms predicted MD. These results highlight the role of NT in predicting appearance variables in men.

  19. The effects of exposure to slender and muscular images on male body dissatisfaction.

    PubMed

    Galioto, Rachel; Crowther, Janis H

    2013-09-01

    This research examined the effects of appearance-based comparisons to muscular and slender idealized male bodies and the contribution of internalization and social comparison to change in body dissatisfaction. Participants were 111 male undergraduates who completed measures of body dissatisfaction, internalization, and social comparison and viewed images of either muscular or slender men in advertisements or product-only advertisements. Results indicated that exposure to both muscular and slender images was associated with an increase in body dissatisfaction, with no significant differences in the change in body dissatisfaction between the two image conditions. Internalization and trait social comparison were each associated with an increase in body dissatisfaction; however, upward social comparison was only a significant predictor of a change in body dissatisfaction for the males who viewed muscular images. These results highlight the impact of slender models on young men's body dissatisfaction and support the examination of media literacy interventions with this population.

  20. The drive for muscularity in men: media influences and objectification theory.

    PubMed

    Daniel, Samantha; Bridges, Sara K

    2010-01-01

    Presently, objectification theory has yielded mixed results when utilized to explain body image concerns in men. An online survey assessing internalization of media ideals, self-objectification, body surveillance, body shame, the drive for muscularity, and body mass index (BMI) was completed by 244 predominantly college-aged males. Path analyses were used to investigate relationships among these variables where it was hypothesized that objectification variables would mediate the relationship between internalization of media ideals and the drive for muscularity. Internalization of media ideals was the strongest predictor of the drive for muscularity, followed by BMI, though variables of objectification theory had no impact on the drive for muscularity contrary to hypotheses. The results suggest that objectification theory may not be applicable to men as it is currently measured.

  1. Appearance-based comments, body dissatisfaction and drive for muscularity in males.

    PubMed

    Nowell, Carly; Ricciardelli, Lina A

    2008-12-01

    This study examined the role of positive and negative appearance-based comments on body dissatisfaction and drive for muscularity among young adult males. The direct and moderating effect of self-esteem were also investigated; and BMI, age, and social desirability were included as covariates. The participants were 214 males aged between 18 and 30 years. More frequent negative comments were associated with higher body dissatisfaction whilst more frequent positive comments were associated with lower body dissatisfaction. However, both frequent negative and positive commentary were associated with higher drive for muscularity. Self-esteem was also associated with both body dissatisfaction and the drive for muscularity, but it did not moderate that influence of either positive or negative messages. Longitudinal research is now needed to determine the directionality of these relationships. Further research is required to establish the contexts in which positive and negative messages are associated with body dissatisfaction and the drive for muscularity.

  2. Predicting drive for muscularity behavioural engagement from body image attitudes and emotions.

    PubMed

    Tod, David; Edwards, Christian

    2013-01-01

    We examined the potential moderating effects of appearance investment, body image disturbance, and situational body image dysphoria on the drive for muscularity attitude-behaviour relationship. Participants (339 British college men, M(AGE)=20.00 years, SD=2.59) completed drive for muscularity attitude and behaviour, appearance investment, body image disturbance, and situational body image dysphoria measures. Results indicated higher levels of appearance investment, body image disturbance, and situational body image dysphoria were associated with increases in the drive for muscularity attitude's relationship with physique-enhancing behavioural engagement. Results help extend recent research that has moved beyond identifying correlates to examining ways that groups of variables interact to predict drive for muscularity behavioural engagement and may contribute to theory development.

  3. Clinical and genetic diversity of SMN1-negative proximal spinal muscular atrophies

    PubMed Central

    Jordanova, Albena

    2014-01-01

    Hereditary spinal muscular atrophy is a motor neuron disorder characterized by muscle weakness and atrophy due to degeneration of the anterior horn cells of the spinal cord. Initially, the disease was considered purely as an autosomal recessive condition caused by loss-of-function SMN1 mutations on 5q13. Recent developments in next generation sequencing technologies, however, have unveiled a growing number of clinical conditions designated as non-5q forms of spinal muscular atrophy. At present, 16 different genes and one unresolved locus are associated with proximal non-5q forms, having high phenotypic variability and diverse inheritance patterns. This review provides an overview of the current knowledge regarding the phenotypes, causative genes, and disease mechanisms associated with proximal SMN1-negative spinal muscular atrophies. We describe the molecular and cellular functions enriched among causative genes, and discuss the challenges in the post-genomics era of spinal muscular atrophy research. PMID:24970098

  4. The muscular organization of the stomach of capybara (Hydrochoerus hydrochaeris): an architectural view.

    PubMed

    Moraes, Priscilla Teixeira de Barros; de Souza, Wilson Machado; da Silva Neto, Paulo Bezerra; Barretto, Carla Siqueira de Figueiredo; Ribeiro, Antonio Augusto Coppi Maciel

    2005-03-01

    Twenty-two stomachs from adult capybaras were used in this study, and an acid digestion mesoscopic technique was pursued using different concentrations of nitric acid to observe the muscular organization of the stomach. The capybara's stomach possessed a muscular coat composed of four layers or strata: external longitudinal, external oblique, circular and internal oblique. Also, the cardiac and pyloric sphincter muscles were comprised of three or two different layers, respectively. Furthermore, the internal oblique fibres were observed extending from the cardiac portion of the stomach to the smaller curvature, where they participated in the formation of the Ansa cardiaca together with the external longitudinal fibres. This muscular architectural arrangement was compared to that in small rodents (rat, hamster, guinea pig), as well as in rabbits and pigs. In conclusion, the stomach of the capybara has a very particular, complex and defined muscular organization that differs from that in other rodents, or domestic animals, in particular, pigs.

  5. Daily sesame oil supplement attenuates joint pain by inhibiting muscular oxidative stress in osteoarthritis rat model.

    PubMed

    Hsu, Dur-Zong; Chu, Pei-Yi; Jou, I-Ming

    2016-03-01

    Osteoarthritis (OA) is the most common form of arthritis, affecting approximately 15% of the population. The aim of this study was to evaluate the efficacy of sesame oil in controlling OA pain in rats. Rat joint pain was induced by medial meniscal transection in Sprague-Dawley rats and assessed by using hindlimb weight distribution method. Muscular oxidative stress was assessed by determining lipid peroxidation, reactive oxygen species and circulating antioxidants. Sesame oil significantly decreased joint pain compared with positive control group in a dose-dependent manner. Sesame oil decreased lipid peroxidation in muscle but not in serum. Further, sesame oil significantly decreased muscular superoxide anion and peroxynitrite generations but increased muscular glutathione and glutathione peroxidase levels. Further, sesame oil significantly increased nuclear factor erythroid-2-related factor (Nrf2) expression compared with positive control group. We concluded that daily sesame oil supplement may attenuate early joint pain by inhibiting Nrf2-associated muscular oxidative stress in OA rat model.

  6. Reconstruction Approach to a Rare Case of Acquired Scrotal Giant Muscular Hamartoma

    PubMed Central

    Bogetti, Paolo; Rolle, Luigi; Baglioni, Elisabetta Adelaide; Parisi, Andrea; Spaziante, Luca; Rivarossa, Filippo; Ceruti, Carlo; Preto, Mirko; Bocchiotti, Maria Alessandra

    2016-01-01

    Summary: Acquired scrotal giant muscular hamartoma is an uncommon benign lesion with fewer than 10 documented cases all over the world. It is characterized by a proliferation of dermal smooth muscle bundles of scrotum dartos fascia. The authors report a rare case of acquired scrotal giant muscular hamartoma, which occurred in a 70-year-old severely obese and diabetic man presenting with a progressive scrotal enlargement and swelling in the last year, causing marked reduction in quality of life and cosmetic problems. The patient underwent a wide excision of the hamartomatous lesion, and then, a reductive scrotoplasty and autologous skin grafting of penis were performed. Anatomopathological examination showed an acquired scrotal giant muscular hamartoma arising from muscular fascia of dartos. This surgical technique is a valid, safe, effective, and minimally invasive option to treat this pathology, achieving both excellent functional and aesthetic results, with a marked improvement of the patient’s quality of life. PMID:27757322

  7. Spinal Muscular Atrophy Type I: Is It Ethical to Standardize Supportive Care Intervention in Clinical Trials?

    PubMed Central

    Finkel, Richard S.; Bishop, Kathie M.; Nelson, Robert M.

    2016-01-01

    The natural history of spinal muscular atrophy type I (SMA-I) has changed as improved medical support has become available. With investigational drugs for spinal muscular atrophy now in clinical trials, efficient trial design focuses on enrolling recently diagnosed infants, providing best available supportive care, and minimizing subject variation. The quandary has arisen whether it is ethically appropriate to specify a predefined level of nutritional and/or ventilation support for spinal muscular atrophy type I subjects while participating in these studies. We conducted a survey at 2 spinal muscular atrophy investigator meetings involving physician investigators, clinical evaluators, and study coordinators from North America, Europe, and Asia-Pacific. Each group endorsed the concept that having a predefined degree of nutritional and ventilation support was warranted in this context. We discuss how autonomy, beneficence/non-maleficence, noncoercion, social benefit, and equipoise can be maintained when a predefined level of supportive care is proposed, for participation in a clinical trial. PMID:27760875

  8. Cortico-muscular coherence increases with tremor improvement after deep brain stimulation in Parkinson's disease.

    PubMed

    Park, Hame; Kim, June Sic; Paek, Sun Ha; Jeon, Beom Seok; Lee, Jee Young; Chung, Chun Kee

    2009-10-28

    Deep brain stimulation on the subthalamic nucleus has been used to relieve Parkinsonian motor symptoms. However, the underlying physiological mechanism has not been fully understood. Beta-band cortico-muscular coherence increases when healthy humans perform isometric contraction. We hypothesized that this might be a measure of symptomatic improvement in motor performance after subthalamic nucleus deep brain stimulation. Here, we measured the beta-band cortico-muscular coherence with magnetoencephalography from three Parkinson's disease patients. We then compared the coherence values for stimulator on-state and off-state. We found that when the stimulator is on, the beta cortico-muscular coherence elevates significantly for the tremorous hand compared with that when the stimulator is off. This suggests that deep brain stimulation resulted in better cortico-muscular coordination.

  9. Muscular strength is associated with self-esteem in college men but not women.

    PubMed

    Ciccolo, Joseph T; SantaBarbara, Nicholas J; Dunsiger, Shira I; Busch, Andrew M; Bartholomew, John B

    2016-12-01

    Muscular strength is a well-known predictor of morbidity and mortality. Similarly, self-esteem is a predictor of health and well-being. The relationship between these two variables, however, is currently unknown. This study examined the cross-sectional relationship between maximal muscular strength (i.e. handgrip and one-repetition-maximum (1-RM) squat) and global self-esteem in 126 college students. Significant correlations were found between both measures of muscular strength and self-esteem. Further analyses revealed that these relationships were only significant for men. Based on these results, additional research is needed to further explore the relationship between muscular strength and self-esteem, especially in other demographic groups and longitudinally.

  10. Drive for muscularity and drive for thinness: the impact of pro-anorexia websites.

    PubMed

    Juarez, Lilia; Soto, Ernesto; Pritchard, Mary E

    2012-01-01

    In recent years, websites that stress the message of thinness as the ideal and only choice have surfaced on the internet. The possibility that pro-anorexia websites may reinforce restrictive eating and exercise behaviors is an area of concern. In addition, friends may be influencing one another to view these websites, further contributing to drive for thinness in women and drive for muscularity in men. Three hundred male and female undergraduate psychology students responded to questionnaires assessing: internalization of pro-anorexia website content, internalization of general media content, influence of friends to view pro-anorexia websites, peer influence, drive for muscularity, and drive for thinness. Results showed internalization of pro-anorexia website content was positively correlated with drive for thinness in women, and negatively correlated with drive for muscularity in men. Internalization of pro-anorexia website content was found to be related to both drive for thinness in women and drive for muscularity in men.

  11. The effect of thin and muscular images on women's body satisfaction.

    PubMed

    Benton, Catherine; Karazsia, Bryan T

    2015-03-01

    A substantial body of research documents that exposure to images depicting a "thin ideal" body figure effects women's state-oriented body satisfaction. However, there is evidence that the societal ideal body figure of females is evolving to be not just thin, but also muscular or toned. Therefore, the purpose of this research was to test the effect of exposure to ideal body figures that are both thin and muscular on female state body satisfaction. Researchers recruited female participants (N=366) from an online community (Amazon's Mechanical Turk) and randomly assigned them to view images in one of four conditions: thin, thin and muscular, thin and hypermuscular, and control (images of cars). Results indicated that state-oriented body satisfaction decreased in the thin condition and thin and muscular condition, but not the hypermuscular or control conditions. These findings have implications for clinical initiatives as well as future research.

  12. Rimmed vacuoles in Becker muscular dystrophy have similar features with inclusion myopathies.

    PubMed

    Momma, Kazunari; Noguchi, Satoru; Malicdan, May Christine V; Hayashi, Yukiko K; Minami, Narihiro; Kamakura, Keiko; Nonaka, Ikuya; Nishino, Ichizo

    2012-01-01

    Rimmed vacuoles in myofibers are thought to be due to the accumulation of autophagic vacuoles, and can be characteristic in certain myopathies with protein inclusions in myofibers. In this study, we performed a detailed clinical, molecular, and pathological characterization of Becker muscular dystrophy patients who have rimmed vacuoles in muscles. Among 65 Becker muscular dystrophy patients, we identified 12 patients who have rimmed vacuoles and 11 patients who have deletions in exons 45-48 in DMD gene. All patients having rimmed vacuoles showed milder clinical features compared to those without rimmed vacuoles. Interestingly, the rimmed vacuoles in Becker muscular dystrophy muscles seem to represent autophagic vacuoles and are also associated with polyubiquitinated protein aggregates. These findings support the notion that rimmed vacuoles can appear in Becker muscular dystrophy, and may be related to the chronic changes in muscle pathology induced by certain mutations in the DMD gene.

  13. Muscarinic antagonists microinjected into the subthalamic nucleus decrease muscular rigidity in reserpinized rats.

    PubMed

    Hernández-López, S; Flores, G; Rosales, M G; Sierra, A; Martínez-Fong, D; Aceves, J

    1996-08-09

    The ability of anticholinergic agents microinjected into the subthalamic nucleus to reduce reserpine-induced muscular rigidity was assessed in rats. The electromyographical activity of the gastrocnemius-soleus muscle was used as a parameter of muscular rigidity. Reserpine (5 mg/kg i.p.) produced the appearance of electromyographical activity. The muscarinic antagonists M3 (1.27 nmol of 4-DAMP) and M1 (2.36 nmol of pirenzepine) markedly reduced the reserpine-induced electromyographical activity, whereas the M2 antagonist AFDX-116 (2.37 nmol) had no effect. These results suggest that a high cholinergic tone in the subthalamic nucleus is associated with the reserpine-induced muscular rigidity. Moreover, the M3 muscarinic antagonist is more effective than the M1 muscarinic antagonist in reducing the muscular rigidity in reserpinized rats, a model of Parkinson's disease, by blocking the high cholinergic tone in the subthalamic nucleus.

  14. Second generation Robo-AO instruments and systems

    NASA Astrophysics Data System (ADS)

    Baranec, Christoph; Riddle, Reed; Law, Nicholas M.; Chun, Mark R.; Lu, Jessica R.; Connelley, Michael S.; Hall, Donald; Atkinson, Dani; Jacobson, Shane

    2014-07-01

    The prototype Robo-AO system at the Palomar Observatory 1.5-m telescope is the world's first fully automated laser adaptive optics instrument. Scientific operations commenced in June 2012 and more than 12,000 observations have since been performed at the ~0.12" visible-light diffraction limit. Two new infrared cameras providing high-speed tip-tilt sensing and a 2' field-of-view will be integrated in 2014. In addition to a Robo-AO clone for the 2-m IGO and the natural guide star variant KAPAO at the 1-m Table Mountain telescope, a second generation of facility-class Robo-AO systems are in development for the 2.2-m University of Hawai'i and 3-m IRTF telescopes which will provide higher Strehl ratios, sharper imaging, ~0.07", and correction to λ = 400 nm.

  15. Complementary and Alternative Medicine for Duchenne and Becker Muscular Dystrophies: Characteristics of Users and Caregivers

    PubMed Central

    Zhu, Yong; Romitti, Paul A.; Conway, Kristin M.; Andrews, Jennifer; Liu, Ke; Meaney, F. John; Street, Natalie; Puzhankara, Soman; Druschel, Charlotte M.; Matthews, Dennis J.

    2015-01-01

    BACKGROUND Complementary and alternative medicine is frequently used in the management of chronic pediatric diseases, but little is known about its use by those with Duchenne or Becker muscular dystrophy. METHODS Complementary and alternative medicine use by male patients with Duchenne or Becker muscular dystrophy and associations with characteristics of male patients and their caregivers were examined through interviews with 362 primary caregivers identified from the Muscular Dystrophy Surveillance, Tracking, and Research Network. RESULTS Overall, 272 of the 362 (75.1%) primary caregivers reported that they had used any complementary and alternative medicine for the oldest Muscular Dystrophy Surveillance, Tracking, and Research Network male in their family. The most commonly reported therapies were from the mind-body medicine domain (61.0%) followed by those from the biologically based practice (39.2%), manipulative and body-based practice (29.3%), and whole medical system (6.9%) domains. Aquatherapy, prayer and/or blessing, special diet, and massage were the most frequently used therapies. Compared with nonusers, male patients who used any therapy were more likely to have an early onset of symptoms and use a wheel chair; their caregivers were more likely to be non-Hispanic white. Among domains, associations were observed with caregiver education and family income (mind-body medicines [excluding prayer and/or blessing only] and whole medical systems) and Muscular Dystrophy Surveillance, Tracking, and Research Network site (biologically based practices and mind-body medicines [excluding prayer and/or blessing only]). CONCLUSIONS Complementary and alternative medicine use was common in the management of Duchenne and Becker muscular dystrophies among Muscular Dystrophy Surveillance, Tracking, and Research Network males. This widespread use suggests further study to evaluate the efficacy of integrating complementary and alternative medicine into treatment regimens for

  16. Cornerstones in reconstructive plastic surgery: Argentinian development of muscular, myocutaneous, and fasciocutaneous flaps.

    PubMed

    Kostianovsky, A S; Sostaric, N M

    1992-01-01

    This article pays tribute to two Argentinian surgeons whose work has been published in their local journals but is unknown internationally. Goldtraj's pioneering work on the treatment of vascular ulcers of the leg using a muscular flap, presented in 1954, and Spadafora's work on the treatment of tissue defects with myocutaneous and fasciocutaneous flaps, presented in 1964, are discussed. Both papers deserve a place among the pioneering contributions on the subject of muscular as well as myocutaneous and fasciocutaneous flaps.

  17. Translational Studies of GALGT2 Gene Therapy for Duchenne Muscular Dystrophy

    DTIC Science & Technology

    2013-10-01

    Gene Therapy for Duchenne Muscular Dystrophy PRINCIPAL INVESTIGATOR: Paul T. Martin, Ph.D. CONTRACTING ORGANIZATION: The Research...Therapy for Duchenne Muscular Dystrophy 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0416 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Paul T...maximal specific force and force drop during eccentric contractions (Task 3, Milestone 1 and Task 7, Milestone 2) and EDL and TA muscles for

  18. Decreased Insulin Receptors but Normal Glucose Metabolism in Duchenne Muscular Dystrophy

    NASA Astrophysics Data System (ADS)

    de Pirro, Roberto; Lauro, Renato; Testa, Ivano; Ferretti, Ginofabrizio; de Martinis, Carlo; Dellantonio, Renzo

    1982-04-01

    Compared to matched controls, 17 patients with Duchenne muscular dystrophy showed decreased insulin binding to monocytes due to decreased receptor concentration. These patients showed no signs of altered glucose metabolism and retrospective analysis of the clinical records of a further 56 such patients revealed no modification in carbohydrate metabolism. These data suggest that reduced insulin receptor number does not produce overt modifications of glucose metabolism in Duchenne muscular dystrophy.

  19. Standard Operating Procedures (SOPs) for Evaluating the Heart in Preclinical Studies of Duchenne Muscular Dystrophy.

    PubMed

    Duan, Dongsheng; Rafael-Fortney, Jill A; Blain, Alison; Kass, David A; McNally, Elizabeth M; Metzger, Joseph M; Spurney, Christopher F; Kinnett, Kathi

    2016-02-01

    A recent working group meeting focused on contemporary cardiac issues in Duchenne muscular dystrophy (DMD) was hosted by the National Heart, Lung, and Blood Institute in collaboration with the Parent Project Muscular Dystrophy. An outcome of this meeting was to provide freely available detailed protocols for preclinical animal studies. The goal of these protocols is to improve the quality and reproducibility of cardiac preclinical studies aimed at developing new therapeutics for the prevention and treatment of DMD cardiomyopathy.

  20. Proteomics profiling of urine reveals specific titin fragments as biomarkers of Duchenne muscular dystrophy.

    PubMed

    Rouillon, Jeremy; Zocevic, Aleksandar; Leger, Thibaut; Garcia, Camille; Camadro, Jean-Michel; Udd, Bjarne; Wong, Brenda; Servais, Laurent; Voit, Thomas; Svinartchouk, Fedor

    2014-07-01

    Diagnosis of muscular dystrophies is currently based on invasive methods requiring muscle biopsies or blood tests. The aim of the present study was to identify urinary biomarkers as a diagnostic tool for muscular dystrophies. Here, the urinary proteomes of Duchenne muscular dystrophy (DMD) patients and healthy donors were compared with a bottom-up proteomic approach. Label-free analysis of more than 1100 identified proteins revealed that 32 of them were differentially expressed between healthy controls and DMD patients. Among these 32 proteins, titin showed the highest fold change between healthy subjects and DMD patients. Interestingly, most of the sequenced peptides belong to the N-terminal and C-terminal parts of titin, and the presence of the corresponding fragments in the urine of DMD patients was confirmed by Western blot analysis. Analysis of a large cohort of DMD patients and age-matched controls (a total of 104 individuals aged from 3 to 20 years) confirmed presence of the N-ter fragment in all but two patients. In two DMD patients aged 16 and 20 years this fragment was undetectable and two healthy controls of 16 and 19 years with serum CK >800 IU/L demonstrated a low level of the fragment. N- and C-terminal titin fragments were also detected in urine from patients with other muscular dystrophies such as Becker muscular dystrophy and Limb-girdle muscular dystrophy (type 1D, 2D and 2J) but not in neurogenic spinal muscular atrophy. They were also present in urine of dystrophin-deficient animal models (GRMD dogs and mdx mice). Titin is the first urinary biomarker that offers the possibility to develop a simple, non-invasive and easy-to-use test for pre-screening of muscular dystrophies, and may also prove to be useful for the non-invasive follow up of DMD patients under treatment.

  1. Initial Performance of the Keck AO Wavefront Controller System

    SciTech Connect

    Johansson, E M; Acton, D S; An, J R; Avicola, K; Beeman, B V; Brase, J M; Carrano, C J; Gathright, J; Gavel, D T; Hurd, R L; Lai, O; Lupton, W; Macintosh, B A; Max, C E; Olivier, S S; Shelton, J C; Stomski, P J; Tsubota, K; Waltjen, K E; Watson, J A; Wizinowich, P L

    2001-03-01

    The wavefront controller for the Keck Observatory AO system consists of two separate real-time control loops: a tip-tilt control loop to remove tilt from the incoming wavefront, and a deformable mirror control loop to remove higher-order aberrations. In this paper, we describe these control loops and analyze their performance using diagnostic data acquired during the integration and testing of the AO system on the telescope. Disturbance rejection curves for the controllers are calculated from the experimental data and compared to theory. The residual wavefront errors due to control loop bandwidth are also calculated from the data, and possible improvements to the controller performance are discussed.

  2. High-Performance CCSDS AOS Protocol Implementation in FPGA

    NASA Technical Reports Server (NTRS)

    Clare, Loren P.; Torgerson, Jordan L.; Pang, Jackson

    2010-01-01

    The Consultative Committee for Space Data Systems (CCSDS) Advanced Orbiting Systems (AOS) space data link protocol provides a framing layer between channel coding such as LDPC (low-density parity-check) and higher-layer link multiplexing protocols such as CCSDS Encapsulation Service, which is described in the following article. Recent advancement in RF modem technology has allowed multi-megabit transmission over space links. With this increase in data rate, the CCSDS AOS protocol implementation needs to be optimized to both reduce energy consumption and operate at a high rate.

  3. Initial performance of the Keck AO wavefront controller system

    NASA Astrophysics Data System (ADS)

    Johansson, Erik M.; Acton, D. Scott; An, Jong R.; Avicola, Kenneth; Beeman, Bart V.; Brase, James M.; Carrano, Carmen J.; Gathright, John; Gavel, Donald T.; Hurd, Randall L.; Lai, Olivier; Lupton, William; Macintosh, Bruce A.; Max, Claire E.; Olivier, Scot S.; Shelton, J. Christopher; Stomski, Paul J.; Tsubota, Kevin; Waltjen, Kenneth E.; Watson, James A.; Wizinowich, Peter L.

    2000-07-01

    The wavefront controller for the Keck Observatory AO system consists of two separate real-time control loops: a tip-tilt control loop to remove tilt from the incoming wavefront, and a deformable mirror control loop to remove higher-order aberrations. In this paper, we describe these control loops and analyze their performance using diagnostic data acquired during the integration and testing of the AO system on the telescope. Disturbance rejection curves for the controllers are calculated from the experimental data and compared to theory. The residual wavefront errors due to control loop bandwidth are also calculated from the data, and possible improvements to the controller performance are discussed.

  4. Effects of stretching on upper-body muscular performance.

    PubMed

    Torres, Earlando M; Kraemer, William J; Vingren, Jakob L; Volek, Jeff S; Hatfield, Disa L; Spiering, Barry A; Ho, Jen Yu; Fragala, Maren S; Thomas, Gwendolyn A; Anderson, Jeffrey M; Häkkinen, Keijo; Maresh, Carl M

    2008-07-01

    The purpose of this investigation was to examine the influence of upper-body static stretching and dynamic stretching on upper-body muscular performance. Eleven healthy men, who were National Collegiate Athletic Association Division I track and field athletes (age, 19.6 +/- 1.7 years; body mass, 93.7 +/- 13.8 kg; height, 183.6 +/- 4.6 cm; bench press 1 repetition maximum [1RM], 106.2 +/- 23.0 kg), participated in this study. Over 4 sessions, subjects participated in 4 different stretching protocols (i.e., no stretching, static stretching, dynamic stretching, and combined static and dynamic stretching) in a balanced randomized order followed by 4 tests: 30% of 1 RM bench throw, isometric bench press, overhead medicine ball throw, and lateral medicine ball throw. Depending on the exercise, test peak power (Pmax), peak force (Fmax), peak acceleration (Amax), peak velocity (Vmax), and peak displacement (Dmax) were measured. There were no differences among stretch trials for Pmax, Fmax, Amax, Vmax, or Dmax for the bench throw or for Fmax for the isometric bench press. For the overhead medicine ball throw, there were no differences among stretch trials for Vmax or Dmax. For the lateral medicine ball throw, there was no difference in Vmax among stretch trials; however, Dmax was significantly larger (p muscular performance in young adult male athletes, regardless of stretch mode, potentially due to the amount of rest used after stretching before the performances. Since throwing performance was largely unaffected by static or dynamic upper-body stretching, athletes competing in the field events could perform upper-body stretching, if enough time were allowed before the performance. However, prior studies on lower-body musculature have demonstrated dramatic negative effects on speed and power. Therefore, it is

  5. Adaptability and Prediction of Anticipatory Muscular Activity Parameters to Different Movements in the Sitting Position.

    PubMed

    Chikh, Soufien; Watelain, Eric; Faupin, Arnaud; Pinti, Antonio; Jarraya, Mohamed; Garnier, Cyril

    2016-08-01

    Voluntary movement often causes postural perturbation that requires an anticipatory postural adjustment to minimize perturbation and increase the efficiency and coordination during execution. This systematic review focuses specifically on the relationship between the parameters of anticipatory muscular activities and movement finality in sitting position among adults, to study the adaptability and predictability of anticipatory muscular activities parameters to different movements and conditions in sitting position in adults. A systematic literature search was performed using PubMed, Science Direct, Web of Science, Springer-Link, Engineering Village, and EbscoHost. Inclusion and exclusion criteria were applied to retain the most rigorous and specific studies, yielding 76 articles, Seventeen articles were excluded at first reading, and after the application of inclusion and exclusion criteria, 23 were retained. In a sitting position, central nervous system activity precedes movement by diverse anticipatory muscular activities and shows the ability to adapt anticipatory muscular activity parameters to the movement direction, postural stability, or charge weight. In addition, these parameters could be adapted to the speed of execution, as found for the standing position. Parameters of anticipatory muscular activities (duration, order, and amplitude of muscle contractions constituting the anticipatory muscular activity) could be used as a predictive indicator of forthcoming movement. In addition, this systematic review may improve methodology in empirical studies and assistive technology for people with disabilities.

  6. Muscular dystrophy in the Japanese Spitz: an inversion disrupts the DMD and RPGR genes.

    PubMed

    Atencia-Fernandez, Sabela; Shiel, Robert E; Mooney, Carmel T; Nolan, Catherine M

    2015-04-01

    An X-linked muscular dystrophy, with deficiency of full-length dystrophin and expression of a low molecular weight dystrophin-related protein, has been described in Japanese Spitz dogs. The aim of this study was to identify the causative mutation and develop a specific test to identify affected cases and carrier animals. Gene expression studies in skeletal muscle of an affected animal indicated aberrant expression of the Duchenne muscular dystrophy (dystrophin) gene and an anomaly in intron 19 of the gene. Genome-walking experiments revealed an inversion that interrupts two genes on the X chromosome, the Duchenne muscular dystrophy gene and the retinitis pigmentosa GTPase regulator gene. All clinically affected dogs and obligate carriers that were tested had the mutant chromosome, and it is concluded that the inversion is the causative mutation for X-linked muscular dystrophy in the Japanese Spitz breed. A PCR assay that amplifies mutant and wild-type alleles was developed and proved capable of identifying affected and carrier individuals. Unexpectedly, a 7-year-old male animal, which had not previously come to clinical attention, was shown to possess the mutant allele and to have a relatively mild form of the disease. This observation indicates phenotypic heterogeneity in Japanese Spitz muscular dystrophy, a feature described previously in humans and Golden Retrievers. With the availability of a simple, fast and accurate test for Japanese Spitz muscular dystrophy, detection of carrier animals and selected breeding should help eliminate the mutation from the breed.

  7. Erythrocyte alloantigens in the Storrs strain of hereditary muscular dystrophic chickens and segregating testcross progeny.

    PubMed

    Sanders, B G; Kline, K; Briles, W E

    1981-01-01

    The Storrs strain of muscular dystrophic chickens were typed for erythrocyte alloalleles at 10 loci, including the B locus. Gene fixation is present at five loci and expression of the predominate alloantigen varied in frequency from 0.53 to 0.91 at the other five loci tested. The Storrs strain of muscular dystrophic chickens are not fixed at the B locus, expressing the B2/B2 allelic combination 81 percent of the time and B2/B23 the remaining percentage. Testcross progeny segregating for the muscular dystrophy trait did not show any alloantigen associations at the 10 loci examined. No association of the MD train with a particular B genotype could be ascertained. CPK levels as a measure of muscle destruction in the muscular dystrophic testcross progeny segregating at the B locus did not reveal an association with any B haplotype. Serum IgG levels and low Con A response in muscular dystrophic testcross progeny also were not associated with any specific B locus alloantigen combinations. The possibility remains that the establishment of a pathological index for muscular dystrophy in MD chickens may reveal an association with the B locus.

  8. Exercise and muscular dystrophy: implications and analysis of effects on musculoskeletal and cardiovascular systems.

    PubMed

    Barnabei, Matthew S; Martindale, Joshua M; Townsend, DeWayne; Metzger, Joseph M

    2011-07-01

    The muscular dystrophies are a heterogeneous collection of progressive, inherited diseases of muscle weakness and degeneration. Although these diseases can vary widely in their etiology and presentation, nearly all muscular dystrophies cause exercise intolerance to some degree. Here, we focus on Duchenne muscular dystrophy (DMD), the most common form of muscular dystrophy, as a paradigm for the effects of muscle disease on exercise capacity. First described in the mid-1800s, DMD is a rapidly progressive and lethal muscular dystrophy caused by mutations in the dystrophin gene. Dystrophin is a membrane-associated cytoskeletal protein, the loss of which causes numerous cellular defects including mechanical instability of the sarcolemma, increased influx of extracellular calcium, and cell signaling defects. Here, we discuss the physiological basis for exercise intolerance in DMD, focusing on the molecular and cellular defects caused by loss of dystrophin and how these manifest as organ-level dysfunction and reduced exercise capacity. The main focus of this article is the defects present in dystrophin-deficient striated muscle. However, discussion regarding the effects of dystrophin loss on other tissues, including vascular smooth muscle is also included. Collectively, the goal of this article is to summarize the current state of knowledge regarding the mechanistic basis for exercise intolerance in DMD, which may serve as an archetype for other muscular dystrophies and diseases of muscle wasting.

  9. Connective tissue growth factor is overexpressed in muscles of human muscular dystrophy.

    PubMed

    Sun, Guilian; Haginoya, Kazuhiro; Wu, Yanling; Chiba, Yoko; Nakanishi, Tohru; Onuma, Akira; Sato, Yuko; Takigawa, Masaharu; Iinuma, Kazuie; Tsuchiya, Shigeru

    2008-04-15

    The detailed process of how dystrophic muscles are replaced by fibrotic tissues is unknown. In the present study, the immunolocalization and mRNA expression of connective tissue growth factor (CTGF) in muscles from normal and dystrophic human muscles were examined with the goal of elucidating the pathophysiological function of CTGF in muscular dystrophy. Biopsies of frozen muscle from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, congenital muscular dystrophy, spinal muscular atrophy, congenital myopathy were analyzed using anti-CTGF polyclonal antibody. Reverse transcription-polymerase chain reaction (RT-PCR) was also performed to evaluate the expression of CTGF mRNA in dystrophic muscles. In normal muscle, neuromuscular junctions and vessels were CTGF-immunopositive, which suggests a physiological role for CTGF in these sites. In dystrophic muscle, CTGF immunoreactivity was localized to muscle fiber basal lamina, regenerating fibers, and the interstitium. Triple immunolabeling revealed that activated fibroblasts were immunopositive for CTGF and transforming growth factor-beta1 (TGF-beta1). RT-PCR analysis revealed increased levels of CTGF mRNA in the muscles of DMD patients. Co-localization of TGF-beta1 and CTGF in activated fibroblasts suggests that CTGF expression is regulated by TGF-beta1 through a paracrine/autocrine mechanism. In conclusion, TGF-beta1-CTGF pathway may play a role in the fibrosis that is commonly observed in muscular dystrophy.

  10. Muscular forearm activation in hand-grip tasks with superimposition of mechanical vibrations.

    PubMed

    Fattorini, L; Tirabasso, A; Lunghi, A; Di Giovanni, R; Sacco, F; Marchetti, E

    2016-02-01

    The purpose of this paper is to evaluate the muscular activation of the forearm, with or without vibration stimuli at different frequencies while performing a grip tasks of 45s at various level of exerted force. In 16 individuals, 9 females and 7 males, the surface electromyogram (EMG) of extensor carpi radialis longus and the flexor carpi ulnari muscles were assessed. At a short latency from onset EMG, RMS and the level of MU synchronization were assessed to evaluate the muscular adaptations. Whilst a trend of decay of EMG Median frequency (MDFd) was employed as an index of muscular fatigue. Muscular tasks consists of the grip of an instrumented handle at a force level of 20%, 30%, 40%, 60% of the maximum voluntary force. Vibration was supplied by a shaker to the hand in mono-frequential waves at 20, 30, 33 and 40Hz. In relation to EMG, RMS and MU synchronization, the muscular activation does not seem to change with the superimposition of the mechanical vibrations, on the contrary a lower MDFd was observed at 33Hz than in absence of vibration. This suggests an early muscular fatigue induced by vibration due to the fact that 33Hz is a resonance frequency for the hand-arm system.

  11. A Prediction of the Damping Properties of Hindered Phenol AO-60/polyacrylate Rubber (AO-60/ACM) Composites through Molecular Dynamics Simulation

    NASA Astrophysics Data System (ADS)

    Yang, Da-Wei; Zhao, Xiu-Ying; Zhang, Geng; Li, Qiang-Guo; Wu, Si-Zhu

    2016-05-01

    Molecule dynamics (MD) simulation, a molecular-level method, was applied to predict the damping properties of AO-60/polyacrylate rubber (AO-60/ACM) composites before experimental measures were performed. MD simulation results revealed that two types of hydrogen bond, namely, type A (AO-60) -OH•••O=C- (ACM), type B (AO-60) - OH•••O=C- (AO-60) were formed. Then, the AO-60/ACM composites were fabricated and tested to verify the accuracy of the MD simulation through dynamic mechanical thermal analysis (DMTA). DMTA results showed that the introduction of AO-60 could remarkably improve the damping properties of the composites, including the increase of glass transition temperature (Tg) alongside with the loss factor (tan δ), also indicating the AO-60/ACM(98/100) had the best damping performance amongst the composites which verified by the experimental.

  12. Factors in delayed onset muscular soreness of man.

    PubMed

    Bobbert, M F; Hollander, A P; Huijing, P A

    1986-02-01

    In this study 11 subjects performed exercise resulting in delayed onset muscular soreness in m. gastrocnemius with one leg, the experimental leg. The other leg served as control. Pre-exercise and 24, 48 and 72 h postexercise, soreness perception, resting EMG level of m. gastrocnemius, and volume and skin temperature of both legs were measured, and a leukocyte count was performed. Perception of soreness in m. gastrocnemius reported 24, 48, and 72 h postexercise was not accompanied by an increase in resting EMG level. This result indicates that soreness perception is not related to a tonic localized spasm in sore muscles. A rise in volume of the experimental leg relative to volume of the control leg was found 24, 48, and 72 h postexercise (P less than 0.05). It is suggested that the volume rise is due to edema formation in the experimental leg and that this edema formation is responsible for soreness perception. Since granulocytosis was not found, the hypothesis that edema formation reflects muscle inflammation is not substantiated.

  13. Outcomes of asymmetry in infants with congenital muscular torticollis

    PubMed Central

    Lee, KyeongSoo; Chung, EunJung; Koh, SeongEun; Lee, Byoung-Hee

    2015-01-01

    [Purpose] The purpose of this study was to assess the outcomes of asymmetry in infants with congenital muscular torticollis (CMT). [Subjects] A total of 102 patients with CMT under the age of 6 months were studied. [Methods] Asymmety was evaluated by determining the difference in the thicknesses of the two sternocleidomastoid muscles (DTSM) using ultrasonography, head tilt (HT) based on a physical examination, and the torticollis overall assessment (TOA). Patients received ultrasound and massage therapy for 30 minutes, in conjunction with passive stretching exercises, 3 times a week. [Results] The DTSM, HT, and TOA scores were significantly different after treatment. Pretest DTSM, HT, and TOA scores and pre-posttest change scores for DTSM, HT, and TOA scores were correlated with treatment duration in infants with CMT. [Conclusion] The findings of this study suggest that treatment duration is correlated with asymmetry evaluation parameters (DTSM, HT, and TOA) in infants with CMT. We propose that these results will help in reducing the treatment duration, and also in improving communication between doctors and therapists during the diagnosis and evaluation of torticollis. PMID:25729191

  14. Tendon Extracellular Matrix Alterations in Ullrich Congenital Muscular Dystrophy

    PubMed Central

    Sardone, Francesca; Traina, Francesco; Bondi, Alice; Merlini, Luciano; Santi, Spartaco; Maraldi, Nadir Mario; Faldini, Cesare; Sabatelli, Patrizia

    2016-01-01

    Collagen VI (COLVI) is a non-fibrillar collagen expressed in skeletal muscle and most connective tissues. Mutations in COLVI genes cause two major clinical forms, Bethlem myopathy and Ullrich congenital muscular dystrophy (UCMD). In addition to congenital muscle weakness, patients affected by COLVI myopathies show axial and proximal joint contractures and distal joint hypermobility, which suggest the involvement of the tendon function. We examined a peroneal tendon biopsy and tenocyte culture of a 15-year-old patient affected by UCMD with compound heterozygous COL6A2 mutations. In patient’s tendon biopsy, we found striking morphological alterations of tendon fibrils, consisting in irregular profiles and reduced mean diameter. The organization of the pericellular matrix of tenocytes, the primary site of collagen fibril assembly, was severely affected, as determined by immunoelectron microscopy, which showed an abnormal accumulation of COLVI and altered distribution of collagen I (COLI) and fibronectin (FBN). In patient’s tenocyte culture, COLVI web formation and cell surface association were severely impaired; large aggregates of COLVI, which matched with COLI labeling, were frequently detected in the extracellular matrix. In addition, metalloproteinase MMP-2, an extracellular matrix-regulating enzyme, was increased in the conditioned medium of patient’s tenocytes, as determined by gelatin zymography and western blot. Altogether, these data indicate that COLVI deficiency may influence the organization of UCMD tendon matrix, resulting in dysfunctional fibrillogenesis. The alterations of tendon matrix may contribute to the complex pathogenesis of COLVI related myopathies. PMID:27375477

  15. Pathways Implicated in Tadalafil Amelioration of Duchenne Muscular Dystrophy.

    PubMed

    De Arcangelis, Valeria; Strimpakos, Georgios; Gabanella, Francesca; Corbi, Nicoletta; Luvisetto, Siro; Magrelli, Armando; Onori, Annalisa; Passananti, Claudio; Pisani, Cinzia; Rome, Sophie; Severini, Cinzia; Naro, Fabio; Mattei, Elisabetta; Di Certo, Maria Grazia; Monaco, Lucia

    2016-01-01

    Numerous therapeutic approaches for Duchenne and Becker Muscular Dystrophy (DMD and BMD), the most common X-linked muscle degenerative disease, have been proposed. So far, the only one showing a clear beneficial effect is the use of corticosteroids. Recent evidence indicates an improvement of dystrophic cardiac and skeletal muscles in the presence of sustained cGMP levels secondary to a blocking of their degradation by phosphodiesterase five (PDE5). Due to these data, we performed a study to investigate the effect of the specific PDE5 inhibitor, tadalafil, on dystrophic skeletal muscle function. Chronic pharmacological treatment with tadalafil has been carried out in mdx mice. Behavioral and physiological tests, as well as histological and biochemical analyses, confirmed the efficacy of the therapy. We then performed a microarray-based genomic analysis to assess the pattern of gene expression in muscle samples obtained from the different cohorts of animals treated with tadalafil. This scrutiny allowed us to identify several classes of modulated genes. Our results show that PDE5 inhibition can ameliorate dystrophy by acting at different levels. Tadalafil can lead to (1) increased lipid metabolism; (2) a switch towards slow oxidative fibers driven by the up-regulation of PGC-1α; (3) an increased protein synthesis efficiency; (4) a better actin network organization at Z-disk.

  16. Muscle Activation during Gait in Children with Duchenne Muscular Dystrophy

    PubMed Central

    Vuillerot, Carole; Tiffreau, Vincent; Peudenier, Sylviane; Cuisset, Jean-Marie; Pereon, Yann; Leboeuf, Fabien; Delporte, Ludovic; Delpierre, Yannick; Gross, Raphaël

    2016-01-01

    The aim of this prospective study was to investigate changes in muscle activity during gait in children with Duchenne muscular Dystrophy (DMD). Dynamic surface electromyography recordings (EMGs) of 16 children with DMD and pathological gait were compared with those of 15 control children. The activity of the rectus femoris (RF), vastus lateralis (VL), medial hamstrings (HS), tibialis anterior (TA) and gastrocnemius soleus (GAS) muscles was recorded and analysed quantitatively and qualitatively. The overall muscle activity in the children with DMD was significantly different from that of the control group. Percentage activation amplitudes of RF, HS and TA were greater throughout the gait cycle in the children with DMD and the timing of GAS activity differed from the control children. Significantly greater muscle coactivation was found in the children with DMD. There were no significant differences between sides. Since the motor command is normal in DMD, the hyper-activity and co-contractions likely compensate for gait instability and muscle weakness, however may have negative consequences on the muscles and may increase the energy cost of gait. Simple rehabilitative strategies such as targeted physical therapies may improve stability and thus the pattern of muscle activity. PMID:27622734

  17. Optimization of Spinal Muscular Atrophy subject's muscle activity during gait

    NASA Astrophysics Data System (ADS)

    Umat, Gazlia; Rambely, Azmin Sham

    2014-06-01

    Spinal Muscular Atrophy (SMA) is a hereditary disease related muscle nerve disorder caused by degeneration of the anterior cells of the spinal cord. SMA is divided into four types according to the degree of seriousness. SMA patients show different gait with normal people. Therefore, this study focused on the effects of SMA patient muscle actions and the difference that exists between SMA subjects and normal subjects. Therefore, the electromyography (EMG) test will be used to track the behavior of muscle during walking and optimization methods are used to get the muscle stress that is capable of doing the work while walking. Involved objective function is non-linear function of the quadratic and cubic functions. The study concludes with a comparison of the objective function using the force that sought to use the moment of previous studies and the objective function using the data obtained from EMG. The results shows that the same muscles, peroneus longus and bisepsfemoris, were used during walking activity by SMA subjects and control subjects. Muscle stress force best solution achieved from part D in simulation carried out.

  18. Muscular dystrophy in girls with X;autosome translocations.

    PubMed Central

    Boyd, Y; Buckle, V; Holt, S; Munro, E; Hunter, D; Craig, I

    1986-01-01

    Twenty known cases of X;autosome translocations with breakpoints at Xp21 associated with Duchenne or Becker muscular dystrophy in girls are reviewed. The variable severity described for different persons may reflect differences in X inactivation or in the nature of the genomic target disrupted. High resolution cytogenetic studies on 12 cases indicate breakpoints on the X chromosome at Xp21.1 or Xp21.2. Translocation chromosomes from several of these cases have been isolated in human/mouse somatic cell hybrids. Molecular heterogeneity in the breakpoint positions has been established by probing DNA from these hybrids with a range of cloned sequences known to be located within, or closely linked to, the Duchenne region. The minimum separation between the most distal and the most proximal breakpoints is 176 kb suggesting that, if a single gene is involved, it must be large. Alternatively, the translocations may affect different genes, or confer alterations to regulatory sequences which operate at a distance. Images PMID:3806636

  19. Clinical Usefulness of Sonoelastography in Infants With Congenital Muscular Torticollis

    PubMed Central

    Hong, Seong Kyung; Song, Jin Won; Woo, Seung Beom; Kim, Jong Min; Kim, Tae Eun

    2016-01-01

    Objective To evaluate the clinical usefulness of sonoelastography in infants with congenital muscular torticollis (CMT). Methods The medical records of 215 infants clinically diagnosed with CMT were retrospectively reviewed. Fifty-three infants met the inclusion criteria as follows: 1) infants diagnosed as CMT with a palpable neck mass before 3 months of age, 2) infants who were evaluated initially by both B-mode ultrasonography and sonoelastography, and 3) infants who had received physical therapy after being diagnosed with CMT. We checked the thickness of the sternocleidomastoid (SCM) muscles in B-mode ultrasonography, strain ratio of the SCM muscles in sonoelastography, and treatment duration. We evaluated the correlation between the treatment duration and the following factors: SCM muscle thickness, ratio of SCM muscle thickness on the affected to unaffected side (A/U ratio), and strain ratio. Results Both the thickness of the affected SCM muscle and the A/U ratio did not show significant correlation with the treatment duration (p=0.66, p=0.90). The strain ratio of the affected SCM muscle was significantly greater than that of the unaffected SCM muscle (p<0.001), and the strain ratio showed significant correlation with the treatment duration (p=0.001). Conclusion Sonoelastography may be a useful adjunctive tool to B-mode ultrasonography for evaluating infants with CMT, especially when predicting their rehabilitation outcomes. PMID:26949666

  20. Feeding problems and malnutrition in spinal muscular atrophy type II.

    PubMed

    Messina, Sonia; Pane, Marika; De Rose, Paola; Vasta, Isabella; Sorleti, Domenica; Aloysius, Annie; Sciarra, Federico; Mangiola, Fortunato; Kinali, Maria; Bertini, Enrico; Mercuri, Eugenio

    2008-05-01

    The aim of the study was to conduct a survey using a dedicated questionnaire to assess feeding difficulties and weight gain in a population of 122 Spinal Muscular Atrophy (SMA) type II patients, aged between 1 and 47 years. All the answers were entered in a database and were analysed subdividing the cohort into age groups (1-5, 6-10, 11-14, 15-19, 20-29, and 30-50 years). Six out of our 122 patients (5%), all younger than 11 years, had weights more than 2SD above the median for age matched controls, whilst 45 (37%) had weights less than 2SD below the median. Chewing difficulties were reported in 34 of the 122 patients (28%) and limitation in the ability to open the mouth in 36 (30%) and both were increasingly more frequent with age. Swallowing difficulties were reported in 30 patients (25%). The results of our survey suggest that a number of patients with SMA type II have limited jaw opening, and chewing and swallowing difficulties. Our findings raise a few issues concerning standards of care that should be implemented in the monitoring and management of feeding difficulties and weight gain.

  1. Placental Development in a Mouse Model of Spinal Muscular Atrophy

    PubMed Central

    Van Granigen Caesar, Gerialisa; Dale, Jeffrey M.; Osman, Erkan Y.; Garcia, Michael L.; Lorson, Christian L.; Schulz, Laura C.

    2016-01-01

    Spinal Muscular Atrophy (SMA) is an autosomal recessive disorder, leading to fatal loss of motor neurons. It is caused by loss of function of the SMN gene, which is expressed throughout the body, and there is increasing evidence of dysfunction in non-neuronal tissues. Birthweight is one of most powerful prognostic factors for infants born with SMA, and intrauterine growth restriction is common. In the SMNΔ7 mouse model of SMA, pups with the disease lived 25% longer when their mothers were fed a higher fat, “breeder” diet. The placenta is responsible for transport of nutrients from mother to fetus, and is a major determinant of fetal growth. Thus, the present study tested the hypothesis that placental development is impaired in SMNΔ7 conceptuses. Detailed morphological characterization revealed no defects in SMNΔ7 placental development, and expression of key transcription factors regulating mouse placental development was unaffected. The intrauterine growth restriction observed in SMA infants likely does not result from impaired placental development. PMID:26748185

  2. Tendon Extracellular Matrix Alterations in Ullrich Congenital Muscular Dystrophy.

    PubMed

    Sardone, Francesca; Traina, Francesco; Bondi, Alice; Merlini, Luciano; Santi, Spartaco; Maraldi, Nadir Mario; Faldini, Cesare; Sabatelli, Patrizia

    2016-01-01

    Collagen VI (COLVI) is a non-fibrillar collagen expressed in skeletal muscle and most connective tissues. Mutations in COLVI genes cause two major clinical forms, Bethlem myopathy and Ullrich congenital muscular dystrophy (UCMD). In addition to congenital muscle weakness, patients affected by COLVI myopathies show axial and proximal joint contractures and distal joint hypermobility, which suggest the involvement of the tendon function. We examined a peroneal tendon biopsy and tenocyte culture of a 15-year-old patient affected by UCMD with compound heterozygous COL6A2 mutations. In patient's tendon biopsy, we found striking morphological alterations of tendon fibrils, consisting in irregular profiles and reduced mean diameter. The organization of the pericellular matrix of tenocytes, the primary site of collagen fibril assembly, was severely affected, as determined by immunoelectron microscopy, which showed an abnormal accumulation of COLVI and altered distribution of collagen I (COLI) and fibronectin (FBN). In patient's tenocyte culture, COLVI web formation and cell surface association were severely impaired; large aggregates of COLVI, which matched with COLI labeling, were frequently detected in the extracellular matrix. In addition, metalloproteinase MMP-2, an extracellular matrix-regulating enzyme, was increased in the conditioned medium of patient's tenocytes, as determined by gelatin zymography and western blot. Altogether, these data indicate that COLVI deficiency may influence the organization of UCMD tendon matrix, resulting in dysfunctional fibrillogenesis. The alterations of tendon matrix may contribute to the complex pathogenesis of COLVI related myopathies.

  3. The Congenital Muscular Dystrophies: Recent Advances and Molecular Insights

    PubMed Central

    Mendell, Jerry R.; Boué, Daniel R.; Martin, Paul T.

    2010-01-01

    Over the past decade, molecular understanding of the congenital muscular dystrophies (CMDs) has greatly expanded. The diseases can be classified into 3 major groups based on the affected genes and the location of their expressed protein: abnormalities of extracellular matrix proteins (LAMA2, COL6A1, COL6A2, COL6A3), abnormalities of membrane receptors for the extracellular matrix (fukutin, POMGnT1, POMT1, POMT2, FKRP, LARGE, and ITGA7), and abnormal endoplasmic reticulum protein (SEPN1). The diseases begin in the perinatal period or shortly thereafter. A specific diagnosis can be challenging because the muscle pathology is usually not distinctive. Immunostaining of muscle using a battery of antibodies can help define a disorder that will need confirmation by gene testing. In muscle diseases with overlapping pathological features, such as CMD, careful attention to the clinical clues (e.g., family history, central nervous system features) can help guide the battery of immunostains necessary to target an unequivocal diagnosis. PMID:17163796

  4. Defects in Motoneuron-Astrocyte Interactions in Spinal Muscular Atrophy.

    PubMed

    Zhou, Chunyi; Feng, Zhihua; Ko, Chien-Ping

    2016-02-24

    Spinal muscular atrophy (SMA) is a motoneuron disease caused by loss or mutation in Survival of Motor Neuron 1 (SMN1) gene. Recent studies have shown that selective restoration of SMN protein in astrocytes partially alleviates pathology in an SMA mouse model, suggesting important roles for astrocytes in SMA. Addressing these underlying mechanisms may provide new therapeutic avenues to fight SMA. Using primary cultures of pure motoneurons or astrocytes from SMNΔ7 (SMA) and wild-type (WT) mice, as well as their mixed and matched cocultures, we characterized the contributions of motoneurons, astrocytes, and their interactions to synapse loss in SMA. In pure motoneuron cultures, SMA motoneurons exhibited normal survival but intrinsic defects in synapse formation and synaptic transmission. In pure astrocyte cultures, SMA astrocytes exhibited defects in calcium homeostasis. In motoneuron-astrocyte contact cocultures, synapse formation and synaptic transmission were significantly reduced when either motoneurons, astrocytes or both were from SMA mice compared with those in WT motoneurons cocultured with WT astrocytes. The reduced synaptic activity is unlikely due to changes in motoneuron excitability. This disruption in synapse formation and synaptic transmission by SMN deficiency was not detected in motoneuron-astrocyte noncontact cocultures. Additionally, we observed a downregulation of Ephrin B2 in SMA astrocytes. These findings suggest that there are both cell autonomous and non-cell-autonomous defects in SMA motoneurons and astrocytes. Defects in contact interactions between SMA motoneurons and astrocytes impair synaptogenesis seen in SMA pathology, possibly due to the disruption of the Ephrin B2 pathway.

  5. Leg muscle involvement in facioscapulohumeral muscular dystrophy assessed by MRI.

    PubMed

    Olsen, David B; Gideon, Peter; Jeppesen, Tina Dysgaard; Vissing, John

    2006-11-01

    Using MRI, we evaluated the degree of involvement of muscles in the lower extremities of 18 unselected patients with facioscapulohumeral muscular dystrophy (FSHD). Findings were correlated with fragment size of the mutated gene, age, disease duration and muscle power. Most affected muscles were the hamstrings followed by the tibialis anterior and the medial gastrocnemius. The vastus-, gluteal- and peroneal muscles were the most unaffected, and the psoas muscle did not show evidence of involvement in any of the investigated subjects. Asymmetric involvement was evident in 15% of the investigated muscles on MRI and 6% on manual muscle strength testing. MRI findings in muscle tended to correlate with disease duration (r = 0.49; p < 0.05), but not with gene fragment size or age. MRI disclosed involvement of muscles performing hip flexion and ankle dorsal flexion that could not be detected by manual muscle strength testing. Otherwise, there was a close correlation (approximately r = 0.75; p < 0.0001) between muscle strength and MRI severity score for other muscle groups. The present study shows that MRI may disclose muscle involvement in FSHD that is not apparent on manual muscle testing, and suggests that MRI of muscle may be an important assessment tool in clinical trials involving patients with FSHD.

  6. Resistance Strength Training Exercise in Children with Spinal Muscular Atrophy

    PubMed Central

    Lewelt, Aga; Krosschell, Kristin J.; Stoddard, Gregory J.; Weng, Cindy; Xue, Mei; Marcus, Robin L.; Gappmaier, Eduard; Viollet, Louis; Johnson, Barbara A.; White, Andrea T.; Viazzo-Trussell, Donata; Lopes, Philippe; Lane, Robert H.; Carey, John C.; Swoboda, Kathryn J.

    2015-01-01

    Introduction Preliminary evidence in adults with spinal muscular atrophy (SMA) and in SMA animal models suggests exercise has potential benefits in improving or stabilizing muscle strength and motor function. Methods We evaluated feasibility, safety, and effects on strength and motor function of a home-based, supervised progressive resistance strength training exercise program in children with SMA types II and III. Up to 14 bilateral proximal muscles were exercised 3 times weekly for 12 weeks. Results Nine children with SMA, aged 10.4±3.8 years, completed the resistance training exercise program. Ninety percent of visits occurred per protocol. Training sessions were pain-free (99.8%), and no study-related adverse events occurred. Trends in improved strength and motor function were observed. Conclusions A 12-week supervised, home-based, 3 days/week progressive resistance training exercise program is feasible, safe, and well tolerated in children with SMA. These findings can inform future studies of exercise in SMA. PMID:25597614

  7. Follistatin Gene Therapy Improves Ambulation in Becker Muscular Dystrophy.

    PubMed

    Al-Zaidy, Samiah A; Sahenk, Zarife; Rodino-Klapac, Louise R; Kaspar, Brian; Mendell, Jerry R

    2015-09-02

    Follistatin is a ubiquitous secretory propeptide that functions as a potent inhibitor of the myostatin pathway, resulting in an increase in skeletal muscle mass. Its ability to interact with the pituitary activin-inhibin axis and suppress the secretion of follicle-stimulating hormone (FSH) called for caution in its clinical applicability. This limitation was circumvented by the use of one of the alternatively spliced follistatin variants, FS344, undergoing post-translational modification to FS315. This follistatin isoform is serum-based, and has a 10-fold lower affinity to activin compared to FS288. Preclinical studies of intramuscular delivery of the follistatin gene demonstrated safety and efficacy in enhancing muscle mass. We herein review the evidence supporting the utility of follistatin as a genetic enhancer to improve cellular performance. In addition, we shed light on the results of the first clinical gene transfer trial using the FS344 isoform of follistatin in subjects with Becker muscular dystrophy as well as the future directions for clinical gene therapy trials using follistatin.

  8. Duchenne muscular dystrophy gene therapy in the canine model.

    PubMed

    Duan, Dongsheng

    2015-03-01

    Duchenne muscular dystrophy (DMD) is an X-linked lethal muscle disease caused by dystrophin deficiency. Gene therapy has significantly improved the outcome of dystrophin-deficient mice. Yet, clinical translation has not resulted in the expected benefits in human patients. This translational gap is largely because of the insufficient modeling of DMD in mice. Specifically, mice lacking dystrophin show minimum dystrophic symptoms, and they do not respond to the gene therapy vector in the same way as human patients do. Further, the size of a mouse is hundredfolds smaller than a boy, making it impossible to scale-up gene therapy in a mouse model. None of these limitations exist in the canine DMD (cDMD) model. For this reason, cDMD dogs have been considered a highly valuable platform to test experimental DMD gene therapy. Over the last three decades, a variety of gene therapy approaches have been evaluated in cDMD dogs using a number of nonviral and viral vectors. These studies have provided critical insight for the development of an effective gene therapy protocol in human patients. This review discusses the history, current status, and future directions of the DMD gene therapy in the canine model.

  9. Disease mechanisms and therapeutic approaches in spinal muscular atrophy.

    PubMed

    Tisdale, Sarah; Pellizzoni, Livio

    2015-06-10

    Motor neuron diseases are neurological disorders characterized primarily by the degeneration of spinal motor neurons, skeletal muscle atrophy, and debilitating and often fatal motor dysfunction. Spinal muscular atrophy (SMA) is an autosomal-recessive motor neuron disease of high incidence and severity and the most common genetic cause of infant mortality. SMA is caused by homozygous mutations in the survival motor neuron 1 (SMN1) gene and retention of at least one copy of the hypomorphic gene paralog SMN2. Early studies established a loss-of-function disease mechanism involving ubiquitous SMN deficiency and suggested SMN upregulation as a possible therapeutic approach. In recent years, greater knowledge of the central role of SMN in RNA processing combined with deep characterization of animal models of SMA has significantly advanced our understanding of the cellular and molecular basis of the disease. SMA is emerging as an RNA disease not limited to motor neurons, but one that involves dysfunction of motor circuits that comprise multiple neuronal subpopulations and possibly other cell types. Advances in SMA research have also led to the development of several potential therapeutics shown to be effective in animal models of SMA that are now in clinical trials. These agents offer unprecedented promise for the treatment of this still incurable neurodegenerative disease.

  10. Similarity of different lifting techniques in trunk muscular synergies.

    PubMed

    Mirakhorlo, Mojtaba; Azghani, Mahmood Reza

    2015-01-01

    Lifting is known to be a major reason for musculoskeletal injuries. In this way, lifting has a crucial effect on human musculoskeletal system and intensity of this impact depends slightly on the selection of techniques. Underlying mechanisms by which trunk muscles are executed during performing lifting are central to biomechanical study of lifting techniques. In the current study, the trunk muscular control mechanisms of lifting are investigated using the synergetic control analysis. Non-negative matrix factorization has been used to extract trunk muscles synergies from their activities - which are computed by a previously validated musculoskeletal model - during different lifting techniques aimed to investigate motor control strategies. Three lifting techniques are considered; stoop, squat and semi-squat. Three synergies account for variety among muscle activation of trunk muscles with related VAF (Variability Account For) of over 95%. Trunk muscle synergy weightings and related time-varying coefficients are calculated for each kind of lifting techniques considering three synergies. Paired correlation coefficients between muscle synergies are all greater than 0.91 (P < 0.05) suggesting that trunk muscle synergies are similar for examined techniques in spite of their kinematic diversity. This similarity can be a result of their common ultimate goal. The acquired results also elucidate the mechanisms of muscle activation patterns that can be exploited in future studies and ergonomic interventions.

  11. [A case of spinal muscular atrophy type 0 in Japan].

    PubMed

    Okamoto, Kentaro; Saito, Kayoko; Sato, Takatoshi; Ishigaki, Keiko; Funatsuka, Makoto; Osawa, Makiko

    2012-09-01

    The patient was a 2-month-old female infant born at 41 weeks and 2 days of gestation presenting multiple arthrogryposis, severe muscle hypotonia and respiratory distress with difficulty in feeding. She suffered from repeated complications with aspiration pneumonia. On admission to our hospital, she exhibited fasciculation and absence of deep tendon reflexes. Examination of the motor nerve conduction velocity (MCV) revealed no muscle contraction. Deletions of the SMN and NAIP genes were noted. Based on severe clinical course and disease development in utero, she was given a diagnosis of spinal muscular atrophy (SMA) type 0 (very severe type). Arthrogryposis and disappearance of MCV are exclusion criteria for SMA. However, the clinical course of the infant was very severe and included such exclusion items. Consequently, when an infant presents muscle hypotonia and respiratory distress, SMA must be considered as one of the differential diagnoses, even though arthrogryposis is an exclusion criterion for SMA. We discuss this case in relation to the few extant reports on SMA type 0 in Japanese infants in the literature.

  12. [Muscular fitness and cardiometabolic risk factors among Colombian young adults].

    PubMed

    Ramírez-Vélez, Robinson; Meneses-Echavez, José F; González-Ruíz, Katherine; Correa, Jorge Enrique

    2014-10-01

    Objetivo: Determinar la relación entre el fitness muscular (FM) con marcadores de riesgo cardio-metabólico en adultos jóvenes de Colombia. Métodos: Un total de 172 hombres (edad 19,7±2,4 años; peso 65,5±10,7 kg; IMC 22,6±2,8 kg•m-1) sin enfermedad cardiovascular previa fueron invitados a participar en el estudio. El FM se determinó mediante el test de dinamometría prensil y los resultados fueron divididos en cuartiles según los valores de FM y FM/peso corporal. Se calculó el índice lipídico-metabólico según las concentraciones de triglicéridos, c-LDL, c-HDL y glucosa. La circunferencia de cintura (CC), porcentaje de grasa, índice de adiposidad corporal (IAC) e índice de masa corporal (IMC) fueron usados como indicadores de adiposidad. Resultados: Después de ajustar por edad, IMC y CC, se observaron relaciones inversas entre el porcentaje de grasa, la CC, los niveles colesterol, HDL-c y LDL-c, con los valores de FM y FM/peso corporal (p.

  13. Beneficial effects of penicillamine treatment on hereditary avian muscular dystrophy.

    PubMed

    Chou, T; Hill, E J; Bartle, E; Woolley, K; LeQuire, V; Olson, W; Roelofs, R; Park, J H

    1975-10-01

    Hereditary muscular dystrophy in chickens of the New Hampshire strain was treated with penicillamine from the 9th day after hatching to the 425th day. The adult maintenance dose for males was 50 mg/kg per day and for females, 13-65 mg/kg per day. In avian dystrophy, deterioration of the muscle fibers is evidenced in the 2nd mo by an inability of the birds to rise after falling on their backs and by a progressive rigidity of the wings. The drug delayed the onset of symptoms and partially alleviated the debilitating aspects of the disease. Penicillamine produced three major improvements: (a) better righting ability when birds were placed on their backs; (b) greater wing flexibility; (c) and suppression of plasma creatine phosphokinase activity. The results are statistically analyzed and discussed in relationship to Duchenne dystrophy. Normal birds were not affected by penicillamine as judged by these parameters. The rationale for using penicillamine, a sulfhydryl compound with reducing properties, was (a) to attempt to protect essential thiol enzymes in the anabolic and glycolytic pathways against inactivation and (b) to prevent collagen cross-linking and deposition in muscle. Although the precise mechanism of drug action has not been determined. the possible role of penicillamine in mitigating the symptoms of genetic dystrophy in man is under consideration. Further, penicillamine may have a more generalized application i the prevention of contractures in a variety of neuromuscular disorders.

  14. Pathogenesis and therapy of spinal and bulbar muscular atrophy (SBMA).

    PubMed

    Katsuno, Masahisa; Tanaka, Fumiaki; Adachi, Hiroaki; Banno, Haruhiko; Suzuki, Keisuke; Watanabe, Hirohisa; Sobue, Gen

    2012-12-01

    Spinal and bulbar muscular atrophy (SBMA) is a late-onset motor neuron disease characterized by slowly progressive muscle weakness and atrophy. During the last two decades, basic and clinical research has provided important insights into the disease phenotype and pathophysiology. The cause of SBMA is the expansion of a trinucleotide CAG repeat encoding a polyglutamine tract within the first exon of the androgen receptor (AR) gene. SBMA exclusively affects adult males, whereas females homozygous for the AR mutation do not manifest neurological symptoms. The ligand-dependent nuclear accumulation of the polyglutamine-expanded AR protein is central to the gender-specific pathogenesis of SBMA, although additional steps, e.g., DNA binding, inter-domain interactions, and post-translational modification of AR, modify toxicity. The interactions with co-regulators are another requisite for the toxic properties of the polyglutamine-expanded AR. It is also shown that the polyglutamine-expanded AR induces diverse molecular events, such as transcriptional dysregulation, axonal transport disruption, and mitochondrial dysfunction, which play causative roles in the neurodegeneration in SBMA. The pathogenic AR-induced myopathy also contributes to the non-cell autonomous degeneration of motor neurons. Pre-clinical studies using animal models show that the pathogenic AR-mediated neurodegeneration is suppressed by androgen inactivation, the efficacy of which has been tested in clinical trials. Pharmacological activation of cellular defense machineries, such as molecular chaperones, ubiquitin-proteasome system, and autophagy, also exerts neuroprotective effects in experimental models of SBMA.

  15. Founder effect in spinal and bulbar muscular atrophy (SBMA).

    PubMed

    Tanaka, F; Doyu, M; Ito, Y; Matsumoto, M; Mitsuma, T; Abe, K; Aoki, M; Itoyama, Y; Fischbeck, K H; Sobue, G

    1996-09-01

    We analyzed the polymorphic (CAG)n and (GGC)n repeats of the androgen receptor gene in 113 unrelated X-linked spinal and bulbar muscular atrophy (SBMA) X chromosomes and 173 control X chromosomes in Japanese males. The control chromosomes had an average CAG repeat number of 21 +/- 3 with a range from 14-32 repeat units, and SBMA chromosomes had a range from 40-55 with a median of 47 +/- 3 copies. The control chromosomes had seven different alleles of the (GGC)n repeat with the range of 11 to 17; the most frequent size of (GGC)n was 16 (79%), while (GGC)17 was very rare (1%). However, in SBMA chromosomes only two alleles were seen; the most frequent size of (GGC)n was 16 (61%) followed by 17 (39%). (GGC)n size distribution was significantly different between SBMA and control chromosomes (P < 0.0001), indicating the presence of linkage disequilibrium. There was no allelic association between the (CAG)n and (GGC)n microsatellites among control subjects as well as SBMA patients, which suggests that a founder effect makes a more significant contribution to generation of Japanese SBMA chromosomes than new mutations.

  16. Transgenic mouse models of spinal and bulbar muscular atrophy (SBMA).

    PubMed

    Katsuno, M; Adachi, H; Inukai, A; Sobue, G

    2003-01-01

    Spinal and bulbar muscular atrophy (SBMA) is a late-onset motor neuron disease characterized by proximal muscle atrophy, weakness, contraction fasciculations, and bulbar involvement. Only males develop symptoms, while female carriers usually are asymptomatic. A specific treatment for SBMA has not been established. The molecular basis of SBMA is the expansion of a trinucleotide CAG repeat, which encodes the polyglutamine (polyQ) tract, in the first exon of the androgen receptor (AR) gene. The pathologic hallmark is nuclear inclusions (NIs) containing the mutant and truncated AR with expanded polyQ in the residual motor neurons in the brainstem and spinal cord as well as in some other visceral organs. Several transgenic (Tg) mouse models have been created for studying the pathogenesis of SBMA. The Tg mouse model carrying pure 239 CAGs under human AR promoter and another model carrying truncated AR with expanded CAGs show motor impairment and nuclear NIs in spinal motor neurons. Interestingly, Tg mice carrying full-length human AR with expanded polyQ demonstrate progressive motor impairment and neurogenic pathology as well as sexual difference of phenotypes. These models recapitulate the phenotypic expression observed in SBMA. The ligand-dependent nuclear localization of the mutant AR is found to be involved in the disease mechanism, and hormonal therapy is suggested to be a therapeutic approach applicable to SBMA.

  17. Reevaluating measures of disease progression in facioscapulohumeral muscular dystrophy.

    PubMed

    Statland, Jeffrey M; McDermott, Michael P; Heatwole, Chad; Martens, William B; Pandya, Shree; van der Kooi, E L; Kissel, John T; Wagner, Kathryn R; Tawil, Rabi

    2013-04-01

    Recent advances in the understanding of the molecular pathophysiology of facioscapulohumeral muscular dystrophy (FSHD) have identified potential therapeutic targets. Consequently, an accurate understanding of disease progression in FSHD is crucial for the design of future clinical trials. Data from 228 subjects in 3 clinical trials and 1 natural history study were compared to examine disease progression in FSHD. All studies utilized the same techniques for manual muscle testing and maximum voluntary isometric contraction testing. Both techniques yield a total strength score that can be followed over time as an indicator of disease progression. Whereas natural history data showed a decrease in strength over 1 year, there was an apparent increase in strength at 6 months in 2 of the 3 clinical trials in both the placebo and treatment groups, that persisted for up to 1 year for maximum voluntary isometric contraction testing. Variability estimates from the clinical trial data were consistent with those seen in the natural history data. Patients in clinical trials in FSHD may have better outcomes than those in natural history studies, regardless of treatment assignment, emphasizing the importance of placebo groups and the need for caution when interpreting the strength results of controlled and uncontrolled trials.

  18. Muscle Pathology Grade for Facioscapulohumeral Muscular Dystrophy Biopsies

    PubMed Central

    Statland, Jeffrey M; Shah, Bharati; Henderson, Don; van der Maarel, Silvere; Tapscott, Stephen J; Tawil, Rabi

    2015-01-01

    Background As we move towards planning for clinical trials in Facioscapulohumeral Muscular Dystrophy (FSHD), a better understanding of the clinical relationship with morphological changes in FSHD muscle biopsies will be important for stratifying patients and understanding post-therapeutic changes in muscle. Methods We performed a prospective cross-sectional study of quadriceps muscle biopsies in 74 genetically confirmed FSHD participants (64 FSHD1, 10 FSHD2). We compared a 12-point muscle pathology grade to genetic mutation, disease severity score, and quantitative myometry. Results Pathology grade had moderate correlations with genetic mutation (rho=−0.45, P<0.001), clinical severity score (rho=0.53, P<0.001), disease duration (rho=0.31, P=0.03), and quantitative myometry (rho=−0.47, P<0.001). We found no difference in the frequency of inflammation between FSHD types 1 and 2. Conclusions The pathology grade of quadriceps muscle may be a useful marker of disease activity in FSHD, and it may have a role in stratification for future clinical trials. PMID:25704033

  19. Therapeutic potential of matrix metalloproteinases in Duchenne muscular dystrophy

    PubMed Central

    Ogura, Yuji; Tajrishi, Marjan M.; Sato, Shuichi; Hindi, Sajedah M.; Kumar, Ashok

    2014-01-01

    Matrix metalloproteinases (MMPs) are secreted proteinases that have physiologic roles in degradation and remodeling of extracellular matrix (ECM) in almost all tissues. However, their excessive production in disease conditions leads to many pathological features including tissue breakdown, inflammation, cell death, and fibrosis. Duchenne Muscular dystrophy (DMD) is a devastating genetic muscle disorder caused by partial or complete loss of cytoskeletal protein dystrophin. Progressive muscle wasting in DMD is accompanied by myofiber necrosis followed by cycles of regeneration and degeneration and inflammation that eventually result in replacement of myofiber by connective and adipose tissues. Emerging evidence suggests that gene expression and the activity of various MMPs are aberrantly regulated in muscle biopsies from DMD patients and in skeletal muscle of animal models of DMD. Moreover, a few studies employing genetic mouse models have revealed that different MMPs play distinct roles in disease progression in DMD. Modulation of the activity of MMPs improves myofiber regeneration and enhances the efficacy of transplantation and engraftment of muscle progenitor cells in dystrophic muscle in mouse models of DMD. Furthermore, recent reports also suggest that some MMPs especially MMP-9 can serve as a biomarker for diagnosis and prognosis of DMD. In this article, we provide a succinct overview of the regulation of various MMPs and their therapeutic importance in DMD. PMID:25364719

  20. Social adjustment in adult males affected with progressive muscular dystrophy.

    PubMed

    Eggers, S; Zatz, M

    1998-02-07

    Adult male patients affected with Becker (BMD, N = 22), limb girdle (LGMD, N = 22) and facioscapulohumeral (FSHMD, N = 18) muscular dystrophy were interviewed to assess for the first time how the disease's severity and recurrence risk (RR) magnitude alter their social adjustment. BMD (X-linked recessive) is the severest form and confers an intermediate RR because all daughters will be carriers, LGMD (autosomal-recessive) is moderately severe with a low RR in the absence of consanguineous marriage, and FSHMD (autosomal-dominant) is clinically the mildest of these three forms of MD but with the highest RR, of 50%. Results of the semistructured questionnaire [WHO (1988): Psychiatric Disability Assessment Schedule] showed no significant difference between the three clinical groups, but more severely handicapped patients as well as patients belonging to lower socioeconomic levels from all clinical groups showed poorer social adjustment. Taken together, myopathic patients displayed intermediate social dysfunction compared to controls and schizophrenics studied by Jablensky [1988: WHO Psychiatric Disability Assessment Schedule]. Since the items of major dysfunction proportion among myopathic patients concern intimate relationships (70%), interest in working among those unemployed (67%), and social isolation (53%), emotional support and social and legal assistance should concentrate on these aspects. Interestingly, the results of this study also suggest that high RRs do not affect relationships to the opposite sex.

  1. Moving towards treatments for spinal muscular atrophy: hopes and limits.

    PubMed

    Wirth, Brunhilde; Barkats, Martine; Martinat, Cecile; Sendtner, Michael; Gillingwater, Thomas H

    2015-09-01

    Spinal muscular atrophy (SMA), one of the most frequent and devastating genetic disorders causing neuromuscular degeneration, has reached the forefront of clinical translation. The quite unique genetic situation of SMA patients, who lack functional SMN1 but carry the misspliced SMN2 copy gene, creates the possibility of correcting SMN2 splicing by antisense oligonucleotides or drugs. Both strategies showed impressive results in pre-clinical trials and are now in Phase II-III clinical trials. SMN gene therapy approaches using AAV9-SMN vectors are also highly promising and have entered a Phase I clinical trial. However, careful analysis of SMA animal models and patients has revealed some limitations that need to be taken very seriously, including: i) a limited time-window for successful therapy delivery, making neonatal screening of SMA mandatory; ii) multi-organ impairment, requiring systemic delivery of therapies; and iii) a potential need for combined therapies that both increase SMN levels and target pathways that preserve/rescue motor neuron function over the lifespan. Meeting these challenges will likely be crucial to cure SMA, instead of only ameliorating symptoms, particularly in its most severe form. This review discusses therapies currently in clinical trials, the hopes for SMA therapy, and the potential limitations of these new approaches.

  2. Spatial cognition in young children with spinal muscular atrophy.

    PubMed

    Rivière, James; Lécuyer, Roger

    2002-01-01

    Success in visuospatial tasks has often been demonstrated in teenagers with spinal muscular atrophy (SMA). However, what has been tested in these studies, with the Wechsler Intelligence Scale for Children-Revised (Wechsler, 1974) performance scale, does not deal with the spatial capacities that co-occur with the advent of self-produced locomotion. Indeed, various studies have shown that occurrence of locomotion in infancy is correlated with the development of visuospatial cognitive competencies, suggesting that locomotor experience might play a central role in spatial development, especially in the realm of manual search for hidden objects. It is thus of interest to assess spatial search skills in SMA young children suffering total deprivation of locomotor experience. Twelve Type-2 SMA children with a mean age of 30 months were compared with controls with respect to their spatial search skills in a memory-for-locations task. In this search task, hiding containers were rotated 180 degrees before search was permitted. The performance obtained with the SMA group did not differ from that obtained in the healthy control group. SMA patients searched correctly for a hidden object in the 3-choice search task. Locomotor impairment does not appear to be a key risk factor for dramatic slowing down or deviation in the development of spatial search skills, as assumed by some authors. Further research is needed to identify the alternative pathways to normal spatial development that are used by SMA young children.

  3. Spectrum of Neuropathophysiology in Spinal Muscular Atrophy Type I

    PubMed Central

    Harding, Brian N.; Kariya, Shingo; Monani, Umrao R.; Chung, Wendy K.; Benton, Maryjane; Yum, Sabrina W.; Tennekoon, Gihan; Finkel, Richard S.

    2014-01-01

    Neuropathological findings within the CNS and PNS in patients with spinal muscular atrophy type I (SMA-I) were examined in relation to genetic, clinical and electrophysiological features. Five infants representing the full clinical spectrum of SMAI were examined clinically for compound motor action potential amplitude and SMN2 gene copy number; morphologic analyses of postmortem CNS, neuromuscular junction and muscle tissue samples were performed and SMN protein was assessed in muscle samples. The 2 clinically most severely affected patients had a single copy of the SMN2 gene; in addition to anterior horn cells, dorsal root ganglia and thalamus, neuronal degeneration in them was widespread in cerebral cortex, basal ganglia, pigmented nuclei, brainstem and cerebellum. Two typical SMA-I patients and a milder case each had 2 copies of the SMN2 gene and more restricted neuropathological abnormalities. Maturation of acetylcholine receptor subunits was delayed and the neuromuscular junctions were abnormally formed in the SMA-1 patients. Thus, the neuropathological findings in human SMA-I are similar to many findings in animal models; factors other than SMN2 copy number modify disease severity. We present a pathophysiologic model for SMA-I as a protein deficiency disease affecting a neuronal network with variable clinical thresholds. Because new treatment strategies improve survival of infants with SMA-I, a better understanding of these factors will guide future treatments. PMID:25470343

  4. [Cascade of gene activation in Landouzy Dejerine muscular dystrophy].

    PubMed

    Belayew, A

    2010-01-01

    Our laboratory studies the Landouzy Dejerine muscular dystrophy or FSHD, a genetic disease which affects 7 in 100,000 individuals. The genetic defect is a deletion on chromosome 4 that decreases the copy number of a repeated DNA element, disturbs chromatin structure and activates the expression of neighbouring genes. The originality of our team has been to identify a gene within the repeated element itself and to show its activation in FSHD muscle cells. This gene expresses DUX4, a transcription factor that targets tens of genes, some of which express other transcription factors which target other genes, leading to a general deregulation. This DUX4-mediated cascade recapitulates by itself the major pathological features of FSHD: muscle atrophy, differentiation defect, oxidative stress... The homologous DUX4c gene located 42 kb from the repeat array expresses a protein that triggers myoblast proliferation. Its high expression level in severe cases of FSHD most probably contributes to the pathology by interfering with myoblast fusion with the muscle fibers at the last steps of muscle regeneration. We are performing global analyses of proteins and metabolites in healthy and FSHD myotubes (collaboration R Wattiez and JM Colet, UMONS) to identify abnormalities and their links with DUX4 or DUX4C.

  5. Follistatin Gene Therapy Improves Ambulation in Becker Muscular Dystrophy

    PubMed Central

    Al-Zaidy, Samiah A.; Sahenk, Zarife; Rodino-Klapac, Louise R.; Kaspar, Brian; Mendell, Jerry R.

    2015-01-01

    Abstract Follistatin is a ubiquitous secretory propeptide that functions as a potent inhibitor of the myostatin pathway, resulting in an increase in skeletal muscle mass. Its ability to interact with the pituitary activin-inhibin axis and suppress the secretion of follicle-stimulating hormone (FSH) called for caution in its clinical applicability. This limitation was circumvented by the use of one of the alternatively spliced follistatin variants, FS344, undergoing post-translational modification to FS315. This follistatin isoform is serum-based, and has a 10-fold lower affinity to activin compared to FS288. Preclinical studies of intramuscular delivery of the follistatin gene demonstrated safety and efficacy in enhancing muscle mass. We herein review the evidence supporting the utility of follistatin as a genetic enhancer to improve cellular performance. In addition, we shed light on the results of the first clinical gene transfer trial using the FS344 isoform of follistatin in subjects with Becker muscular dystrophy as well as the future directions for clinical gene therapy trials using follistatin. PMID:27858738

  6. Transcriptional profiling in facioscapulohumeral muscular dystrophy to identify candidate biomarkers

    PubMed Central

    Rahimov, Fedik; King, Oliver D.; Leung, Doris G.; Bibat, Genila M.; Emerson, Charles P.; Kunkel, Louis M.; Wagner, Kathryn R.

    2012-01-01

    Facioscapulohumeral muscular dystrophy (FSHD) is a progressive neuromuscular disorder caused by contractions of repetitive elements within the macrosatellite D4Z4 on chromosome 4q35. The pathophysiology of FSHD is unknown and, as a result, there is currently no effective treatment available for this disease. To better understand the pathophysiology of FSHD and develop mRNA-based biomarkers of affected muscles, we compared global analysis of gene expression in two distinct muscles obtained from a large number of FSHD subjects and their unaffected first-degree relatives. Gene expression in two muscle types was analyzed using GeneChip Gene 1.0 ST arrays: biceps, which typically shows an early and severe disease involvement; and deltoid, which is relatively uninvolved. For both muscle types, the expression differences were mild: using relaxed cutoffs for differential expression (fold change ≥1.2; nominal P value <0.01), we identified 191 and 110 genes differentially expressed between affected and control samples of biceps and deltoid muscle tissues, respectively, with 29 genes in common. Controlling for a false-discovery rate of <0.25 reduced the number of differentially expressed genes in biceps to 188 and in deltoid to 7. Expression levels of 15 genes altered in this study were used as a “molecular signature” in a validation study of an additional 26 subjects and predicted them as FSHD or control with 90% accuracy based on biceps and 80% accuracy based on deltoids. PMID:22988124

  7. Therapeutic potential of matrix metalloproteinases in Duchenne muscular dystrophy.

    PubMed

    Ogura, Yuji; Tajrishi, Marjan M; Sato, Shuichi; Hindi, Sajedah M; Kumar, Ashok

    2014-01-01

    Matrix metalloproteinases (MMPs) are secreted proteinases that have physiologic roles in degradation and remodeling of extracellular matrix (ECM) in almost all tissues. However, their excessive production in disease conditions leads to many pathological features including tissue breakdown, inflammation, cell death, and fibrosis. Duchenne Muscular dystrophy (DMD) is a devastating genetic muscle disorder caused by partial or complete loss of cytoskeletal protein dystrophin. Progressive muscle wasting in DMD is accompanied by myofiber necrosis followed by cycles of regeneration and degeneration and inflammation that eventually result in replacement of myofiber by connective and adipose tissues. Emerging evidence suggests that gene expression and the activity of various MMPs are aberrantly regulated in muscle biopsies from DMD patients and in skeletal muscle of animal models of DMD. Moreover, a few studies employing genetic mouse models have revealed that different MMPs play distinct roles in disease progression in DMD. Modulation of the activity of MMPs improves myofiber regeneration and enhances the efficacy of transplantation and engraftment of muscle progenitor cells in dystrophic muscle in mouse models of DMD. Furthermore, recent reports also suggest that some MMPs especially MMP-9 can serve as a biomarker for diagnosis and prognosis of DMD. In this article, we provide a succinct overview of the regulation of various MMPs and their therapeutic importance in DMD.

  8. Fixation of Winged Scapula in Facioscapulohumeral Muscular Dystrophy

    PubMed Central

    Giannini, Sandro; Faldini, Cesare; Pagkrati, Stavroula; Grandi, Gianluca; Digennaro, Vitantonio; Luciani, Deianira; Merlini, Luciano

    2007-01-01

    Objective: To verify if stabilizing the scapulothoracic joint without arthrodesis could lead to functional improvement of shoulder range of motion and clinical improvement of winged scapula, we incorporated four additional patients into our previous analysis to determine if the results obtained were long lasting, and to compare this fixation with the other techniques described in the literature, balancing the benefits with the complications. Design: A retrospective study. Participants: Thirteen patients with bilateral winged scapula affected by facioscapulohumeral muscular dystrophy. Nine of these patients had been analyzed in our previous study. Methods: Patients were operated on by bilateral fixing of the scapula to the rib cage using metal wires without arthrodesis (scapulopexy). Results: All patients experienced improvement in active range of motion of the shoulder and all of them had clinical improvement with complete resolution of the winged scapula. In all twenty-six surgical interventions of scapulopexy, a stable and long-lasting fixation of the scapula to the rib cage was achieved.The complications strictly associated to the surgical technique encountered were one pneumothorax, which was resolved spontaneously, and one wire breakage without trauma. Average follow-up was 10 years (range, 3 to 18 years). Conclusion: The scapulopexy used in this extended series of patients consisted of repositioning the scapula and fixing it to four ribs by using metal wires without performing arthrodesis.This technique has a low rate of complications, is reproducible, safe and effective, resulting in clinical and functional improvement. PMID:18056023

  9. Outcomes of asymmetry in infants with congenital muscular torticollis.

    PubMed

    Lee, KyeongSoo; Chung, EunJung; Koh, SeongEun; Lee, Byoung-Hee

    2015-02-01

    [Purpose] The purpose of this study was to assess the outcomes of asymmetry in infants with congenital muscular torticollis (CMT). [Subjects] A total of 102 patients with CMT under the age of 6 months were studied. [Methods] Asymmety was evaluated by determining the difference in the thicknesses of the two sternocleidomastoid muscles (DTSM) using ultrasonography, head tilt (HT) based on a physical examination, and the torticollis overall assessment (TOA). Patients received ultrasound and massage therapy for 30 minutes, in conjunction with passive stretching exercises, 3 times a week. [Results] The DTSM, HT, and TOA scores were significantly different after treatment. Pretest DTSM, HT, and TOA scores and pre-posttest change scores for DTSM, HT, and TOA scores were correlated with treatment duration in infants with CMT. [Conclusion] The findings of this study suggest that treatment duration is correlated with asymmetry evaluation parameters (DTSM, HT, and TOA) in infants with CMT. We propose that these results will help in reducing the treatment duration, and also in improving communication between doctors and therapists during the diagnosis and evaluation of torticollis.

  10. Establishing a standardized therapeutic testing protocol for spinal muscular atrophy.

    PubMed

    Tsai, Li-Kai; Tsai, Ming-Shung; Lin, Tzer-Bin; Hwu, Wuh-Liang; Li, Hung

    2006-11-01

    Several mice models have been created for spinal muscular atrophy (SMA); however, there is still no standard preclinical testing system for the disease. We previously generated type III-specific SMA model mice, which might be suitable for use as a preclinical therapeutic testing system for SMA. To establish such a system and test its applicability, we first created a testing protocol and then applied it as a means to investigate the use of valproic acid (VPA) as a possible treatment for SMA. These SMA mice revealed tail/ear/foot deformity, muscle atrophy, poorer motor performances, smaller compound muscle action potential and lower spinal motoneuron density at the age of 9 to 12 months in comparison with age-matched wild-type littermate mice. In addition, VPA attenuates motoneuron death, increases spinal SMN protein level and partially normalizes motor function in SMA mice. These results suggest that the testing protocol developed here is well suited for use as a standardized preclinical therapeutic testing system for SMA.

  11. Laminin-111: a potential therapeutic agent for Duchenne muscular dystrophy.

    PubMed

    Goudenege, Sébastien; Lamarre, Yann; Dumont, Nicolas; Rousseau, Joël; Frenette, Jérôme; Skuk, Daniel; Tremblay, Jacques P

    2010-12-01

    Duchenne muscular dystrophy (DMD) still needs effective treatments, and myoblast transplantation (MT) is considered as an approach to repair damaged skeletal muscles. DMD is due to the complete loss of dystrophin from muscles. The lack of link between the contracting apparatus and the extracellular matrix leads to frequent damage to the sarcolemma triggering muscle fiber necrosis. Laminins are major proteins in the extracellular matrix. Laminin-111 is normally present in skeletal and cardiac muscles in mice and humans but only during embryonic development. In this study, we showed that intramuscular injection of laminin-111 increased muscle strength and resistance in mdx mice. We also used laminin-111 as a coadjuvant in MT, and we showed this protein decreased considerably the repetitive cycles of degeneration, inflammatory reaction, and regeneration. Moreover, MT is significantly improved. To explain the improvement, we confirmed with the same myoblast cell batch that laminin-111 improves proliferation and drastically increases migration in vitro. These results are extremely important because DMD could be treated only by the injection of a recombinant protein, a simple and safe therapy to prevent loss of muscle function. Moreover, the improvement in MT would be significant to treat the muscles of DMD patients who are already weak.

  12. Chewing pattern and muscular activation in open bite patients.

    PubMed

    Piancino, Maria Grazia; Isola, Gaetano; Merlo, Andrea; Dalessandri, Domenico; Debernardi, Cesare; Bracco, Pietro

    2012-04-01

    Different studies have indicated, in open bite patients, that masticatory muscles tend to generate a small maximum bite force and to show a reduced cross-sectional area with a lower EMG activity. The aim of this study was to evaluate the kinematics parameters of the chewing cycles and the activation of masseters and anterior temporalis muscles of patients with anterior dental open bite malocclusion. There have been no previous reports evaluating both kinematic values and EMG activity of patients with anterior open bite during chewing. Fifty-two young patients (23 boys and 29 girls; mean age±SD 11.5±1.2 and 10.2±1.6years, respectively) with anterior open bite malocclusion and 21 subjects with normal occlusion were selected for the study. Kinematics parameters and surface electromyography (EMG) were simultaneously recorded during chewing a hard bolus with a kinesiograph K7-I Myotronics-Usa. The results showed a statistically significant difference between the open bite patients and the control group for a narrower chewing pattern, a shorter total and closing duration of the chewing pattern, a lower peak of both the anterior temporalis and the masseter of the bolus side. In this study, it has been observed that open bite patients, lacking the inputs from the anterior guidance, that are considered important information for establishing the motor scheme of the chewing pattern, show narrower chewing pattern, shorter lasting chewing cycles and lower muscular activation with respect to the control group.

  13. Muscular Control of Turning and Maneuvering in Jellyfish Bells

    NASA Astrophysics Data System (ADS)

    Hoover, Alexander; Miller, Laura; Griffith, Boyce

    2014-11-01

    Jellyfish represent one of the earliest and simplest examples of swimming by a macroscopic organism. Contractions of an elastic bell that expels water are driven by coronal swimming muscles. The re-expansion of the bell is passively driven by stored elastic energy. A current question in jellyfish propulsion is how the underlying neuromuscular organization of their bell allows for maneuvering. Using an immersed boundary framework, we will examine the mechanics of swimming by incorporating material models that are informed by the musculature present in jellyfish into a model of the elastic jellyfish bell in three dimensions. The fully-coupled fluid structure interaction problem is solved using an adaptive and parallelized version of the immersed boundary method (IBAMR). We then use this model to understand how variability in the muscular activation patterns allows for complicated swimming behavior, such as steering. We will compare the results of the simulations with the actual turning maneuvers of several species of jellyfish. Numerical flow fields will also be compared to those produced by actual jellyfish using particle image velocimetry (PIV).

  14. Vibroacoustic processes and structural variations in muscular tissue

    NASA Astrophysics Data System (ADS)

    Antonets, V. A.; Klochkov, B. N.; Kovaleva, E. P.

    1995-03-01

    This paper reviews the problems and results obtained in the course of experimental and theoretical investigations of the vibroacoustic activity of contracting muscles. Two types of such processes are examined: (1) acoustic vibrations due to the macromolecular recombinations of muscle proteins, which are responsible for the muscle contraction, and (2) acoustic vibrations associated with the finite accuracy and speed of the receptor-effector system that controls the muscle contraction. By investigating the acoustic vibrations, we examine structural recombinations (conformation variations) in macromolecules during mechanochemical reactions. Since chemical reactions of macromolecules are always accompanied by conformational recombinations, the generation mechanism, which is responsible for the contraction processes in a muscular tissue, can also be extended to other macromolecular media. Investigation of infrasound vibrations makes it possible to explore the quality and error of control for the processes in the muscle under different types of loading. Since a living body is controlled via perceptions, the latter can be quantitatively estimated by the parametess of infrasound vibrations.

  15. Genetic inhibition of JNK3 ameliorates spinal muscular atrophy

    PubMed Central

    Genabai, Naresh K.; Ahmad, Saif; Zhang, Zhanying; Jiang, Xiaoting; Gabaldon, Cynthia A.; Gangwani, Laxman

    2015-01-01

    Mutation of the Survival Motor Neuron 1 (SMN1) gene causes spinal muscular atrophy (SMA), an autosomal recessive neurodegenerative disorder that occurs in early childhood. Degeneration of spinal motor neurons caused by SMN deficiency results in progressive muscle atrophy and death in SMA. The molecular mechanism underlying neurodegeneration in SMA is unknown. No treatment is available to prevent neurodegeneration and reduce the burden of illness in SMA. We report that the c-Jun NH2-terminal kinase (JNK) signaling pathway mediates neurodegeneration in SMA. The neuron-specific isoform JNK3 is required for neuron degeneration caused by SMN deficiency. JNK3 deficiency reduces degeneration of cultured neurons caused by low levels of SMN. Genetic inhibition of JNK pathway in vivo by Jnk3 knockout results in amelioration of SMA phenotype. JNK3 deficiency prevents the loss of spinal cord motor neurons, reduces muscle degeneration, improves muscle fiber thickness and muscle growth, improves motor function and overall growth and increases lifespan of mice with SMA that shows a systemic rescue of phenotype by a SMN-independent mechanism. JNK3 represents a potential (non-SMN) therapeutic target for the treatment of SMA. PMID:26423457

  16. Oral approach-avoidance: affective consequences of muscular articulation dynamics.

    PubMed

    Topolinski, Sascha; Maschmann, Ira Theresa; Pecher, Diane; Winkielman, Piotr

    2014-06-01

    Can mouth movements shape attitudes? When people articulate different consonants (e.g., B or K) they press the tongue and the lips against various spots in the mouth. This allows for construction of words that feature systematic wanderings of consonantal stricture spots either from the front to the rear (inward; e.g., BENOKA) or from the rear to the front (outward; e.g., KENOBA) of the mouth. These wanderings of muscular strictures resemble the oral kinematics during either deglution (swallowing-like, inward movement) or expectoration (spitting-like, outward movement). Thus, we predicted that the articulation of inward and outward words induces motivational states associated with deglutition and expectoration--namely, approach and avoidance--which was tested in 9 experiments (total N = 822). Inward words were preferred over outward words, being labeled as nonsense words (Experiments 1, 4, 5, 6, and 9), company names (Experiment 2), or person names (Experiments 3, 7, and 8), with control words falling in between (Experiment 5). As a social-behavioral consequence, ostensible chat partners were more often chosen to interact with when having inward compared to outward names (Experiment 7). The effect was found in German-speaking (Experiments 1-5) and English-speaking (Experiment 6) samples, and it occurred even under silent reading (all experiments) and for negatively labeled targets (names of villains; Experiment 8). Showing articulation simulations as being the causal undercurrent, this effect was absent in aphasia patients who lacked covert subvocalizations (Experiment 9).

  17. Course Material Model in A&O Learning Environment.

    ERIC Educational Resources Information Center

    Levasma, Jarkko; Nykanen, Ossi

    One of the problematic issues in the content development for learning environments is the process of importing various types of course material into the environment. This paper describes a method for importing material into the A&O open learning environment by introducing a material model for metadata recognized by the environment. The first…

  18. [Translation and validation of the Egen Klassifikation scale for the Spanish population: functional assessment for non-ambulatory individuals with Duchenne's muscular dystrophy and spinal muscular atrophy].

    PubMed

    Fagoaga, Joaquín; Girabent-Farrés, Montserrat; Bagur-Calafat, Caritat; Febrer, Anna; Steffensen, Birgit F

    2013-06-01

    Introduccion. La escala Egen Klassifikation (EK) es un cuestionario que valora la capacidad funcional de personas con distrofia muscular de Duchenne y atrofia muscular espinal no ambulantes y que estan en silla de ruedas. Objetivo. Traducir y validar la EK para la poblacion espanola, como instrumento de medicion de la capacidad funcional en dichos pacientes. Pacientes y metodos. Se realiza, en primer lugar, una traduccion-retrotraduccion de la EK en la poblacion espanola y, posteriormente, se practica el estudio de fiabilidad de la version traducida al espanol de dicha escala. Se llevan a cabo tres mediciones a 30 pacientes con edades comprendidas entre 4 y 67 anos. Dos de estas mediciones se realizan por el mismo observador, y la tercera, por un segundo observador, para evaluar la concordancia intra e interobservador. Resultados. Los valores obtenidos referidos a la puntuacion total de los items de la escala, suma EK, reflejan un indice de fiabilidad del 0,995. Tambien muestran una fiabilidad superior a 0,86 en cada uno de los items, tanto en las observaciones intra como interobservador. Conclusiones. La version espanola de la EK es un instrumento valido y fiable para la poblacion espanola, como herramienta de medicion de la capacidad funcional en pacientes con distrofia muscular de Duchenne y atrofia muscular espinal no ambulantes y que estan en silla de ruedas.

  19. Expertise-dependent modulation of muscular and non-muscular torques in multi-joint arm movements during piano keystroke.

    PubMed

    Furuya, S; Kinoshita, H

    2008-10-02

    The problem of skill-level-dependent modulation in the joint dynamics of multi-joint arm movements is addressed in this study using piano keystroke performed by expert and novice piano players. Using the measured kinematic and key-force data, the time varying net, gravitational, motion-dependent interaction (INT), key-reaction (REA), and muscular (MUS) torques at the shoulder, elbow, wrist, and metacarpophalangeal (MP) joints were computed using inverse dynamics techniques. INTs generated at the elbow and wrist joints, but not those at the MP joint, were greater for the experts as compared with the novices. REA at the MP joint, but not at the other joints, was less for the experts as compared with the novices. The MUSs at the MP, wrist, and elbow joints were smaller, and that at the shoulder joint was larger for the experts as compared with the novices. The experts also had a lesser inter-strike variability of key striking force and key descending velocity as compared with the novices. These findings indicated that the relationship among the INT, REA, and MUS occurring at the joints of the upper-extremity differed between the expert and novice piano players, suggesting that the organization of multi-joint arm movement is modulated by long-term motor training toward facilitating both physiological efficiency and movement accuracy.

  20. Altered aquaporin-4 expression in human muscular dystrophies: a common feature?

    PubMed

    Frigeri, Antonio; Nicchia, Grazia Paola; Repetto, Silvia; Bado, Massimo; Minetti, Carlo; Svelto, Maria

    2002-07-01

    Duchenne Muscular Dystrophy (DMD) is a progressive lethal muscle disease that affects young boys. Dystrophin, absent in DMD and reduced in the milder form Becker Muscular Dystrophy (BMD), binds to several membrane-associated proteins known as dystrophin-associated proteins (DAPs). Once this critical structural link is disrupted, muscle fibers become more vulnerable to mechanical and osmotic stress. Recently, we have reported that the expression of aquaporin-4 (AQP4), a water-selective channel expressed in the sarcolemma of fast-twitch fibers and astrocyte end-feet, is drastically reduced in the muscle and brain of the mdx mouse, the animal model of DMD. In the present study, we analyzed the expression of AQP4 in several DMD/BMD patients of different ages with different mutations in the dystrophin gene. Immunofluorescence results indicate that, compared with healthy control children, AQP4 is reduced severely in all the DMD muscular biopsies analyzed and in 50% of the analyzed BMD. Western blot analysis revealed that the deficiency in sarcolemma AQP4 staining is due to a reduction in total AQP4 muscle protein content rather than to changes in immunoreactivity. Double-immunostaining experiments indicate that AQP4 reduction is independent of changes in the fiber myosin heavy chain composition. AQP4 and a-syntrophin analysis of BMD muscular biopsies revealed that the expression and stability of AQP4 in the sarcolemma does not always decrease when a-syntrophin is strongly reduced. Finally, limb-girdle muscular dystrophy biopsies and facioscapulohumeral muscular dystrophy revealed that AQP4 expression was not altered in these forms of muscular dystrophy. These experiments provide the first evidence of AQP4 reduction in a human pathology and show that this deficiency is an important feature of DMD/BMD.

  1. Cold modalities with different thermodynamic properties have similar effects on muscular performance and activation.

    PubMed

    Vieira, A; Oliveira, A B; Costa, J R; Herrera, E; Salvini, T F

    2013-10-01

    Although tissue cooling is widely used in the treatment of musculoskeletal injuries there is still controversy about its effects on muscular performance. The combination of cooling and exercise justifies the study of this topic. The aim was to compare the effects of ice pack and cold-water immersion on the muscular performance parameters of plantar flexors and muscular activation of the triceps surae. 41 healthy men (mean age: 22.1 years, SD: 2.9) were randomly assigned to cooling with either ice pack (n=20) or cold-water immersion (n=21). Independent variables were cold modality (ice pack or cold-water immersion) and pre- and post-cooling measurement time. Dependent variables were muscular performance (measured during isometric and concentric contractions of plantar flexors) and electromyography parameters of the triceps surae (median frequency and root mean square amplitude). Dependent-samples t-tests were used to compare pre- and post-cooling data and independent-samples t-tests were used to compare the difference (pre- and post-cooling) between groups. Ice pack increased isometric peak torque (mean: 9.00 Nm, P=0.01) and both cold modalities reduced muscular activation in triceps surae (P<0.0001); Cold-water immersion and ice pack reduced peak torque and total work during dynamic isokinetic contraction at both velocities (mean: -11,00 Nm, P<0.05) and affected muscular activation in different ways. In conclusion, ice pack increases isometric torque, while both ice pack and cold-water immersion decrease concentric muscular performance. These results indicate that these cooling methods should be chosen with caution, considering the type of task required during training or rehabilitation. New studies investigating other muscle groups and joints are necessary.

  2. Electrophysiological biomarkers in spinal muscular atrophy: proof of concept

    PubMed Central

    David Arnold, W; Porensky, Paul N; McGovern, Vicki L; Iyer, Chitra C; Duque, Sandra; Li, Xiaobai; Meyer, Kathrin; Schmelzer, Leah; Kaspar, Brian K; Kolb, Stephen J; Kissel, John T; Burghes, Arthur H M

    2014-01-01

    Objective Preclinical therapies that restore survival motor neuron (SMN) protein levels can dramatically extend survival in spinal muscular atrophy (SMA) mouse models. Biomarkers are needed to effectively translate these promising therapies to clinical trials. Our objective was to investigate electrophysiological biomarkers of compound muscle action potential (CMAP), motor unit number estimation (MUNE) and electromyography (EMG) using an SMA mouse model. Methods Sciatic CMAP, MUNE, and EMG were obtained in SMNΔ7 mice at ages 3–13 days and at 21 days in mice with SMN selectively reduced in motor neurons (ChATCre). To investigate these measures as biomarkers of treatment response, measurements were obtained in SMNΔ7 mice treated with antisense oligonucleotide (ASO) or gene therapy. Results CMAP was significantly reduced in SMNΔ7 mice at days 6–13 (P < 0.01), and MUNE was reduced at days 7–13 (P < 0.01). Fibrillations were present on EMG in SMNΔ7 mice but not controls (P = 0.02). Similar findings were seen at 21 days in ChATCre mice. MUNE in ASO-treated SMNΔ7 mice were similar to controls at day 12 and 30. CMAP reduction persisted in ASO-treated SMNΔ7 mice at day 12 but was corrected at day 30. Similarly, CMAP and MUNE responses were corrected with gene therapy to restore SMN. Interpretation These studies confirm features of preserved neuromuscular function in the early postnatal period and subsequent motor unit loss in SMNΔ7 mice. SMN restoring therapies result in preserved MUNE and gradual repair of CMAP responses. This provides preclinical evidence for the utilization of CMAP and MUNE as biomarkers in future SMA clinical trials. PMID:24511555

  3. Fibrosis, adipogenesis, and muscle atrophy in congenital muscular torticollis.

    PubMed

    Chen, Huan-Xiong; Tang, Sheng-Ping; Gao, Fu-Tang; Xu, Jiang-Long; Jiang, Xian-Ping; Cao, Juan; Fu, Gui-Bing; Sun, Ke; Liu, Shi-Zhe; Shi, Wei

    2014-11-01

    In the traditional view, muscle atrophy and interstitial fibrosis were regarded as the basic pathological features of congenital muscular torticollis (CMT). But in the ultrastructure study, the mesenchyme-like cells, myoblasts, myofibroblasts, and fibroblasts were found in the proliferation of interstitium of CMT. To investigate the characteristics of pathological features and the mechanisms of muscle atrophy in CMT, we retrospectively reviewed the medical records of 185 CMT patients from July 2009 to July 2011 in Shenzhen Children's Hospital in China and performed pathological studies. According to age, the 185 CMT patients were divided into 4 groups. All resected surgical specimens were processed for hematoxylin and eosin staining and Masson trichromic staining. Sudan III staining was used for frozen sections, whereas immunohistochemical staining for S-100, calpain-1, ubiquitin, and 20S proteasome was carried out on 40 CMT specimens. Eight adductor muscle specimens from 8 patients with development dysplasia of the hip were taken as control group in the immunohistochemical staining. By Masson trichromic staining, the differences in the percent area of fibrous tissue in each CMT groups were significant. In Sudan III staining and immunostaining for S-100, adipocyte hyperplasia was the pathological feature of CMT. Moreover, compared with controls, most atrophic muscle fibers in CMT specimens were found to show strong immunoreactivity for calpain-1, ubiquitin, and 20S proteasome. With increasing age, fibrosis peaked at both sides and it was low in middle age group. Adipocytes increased with age. The characteristics of pathological features in CMT are changeable with age. The calpain and the ubiquitin-proteasome system may play a role in muscle atrophy of CMT. In the CMT, adipogenesis, fibrogenesis, and myogenesis may be the results of mesenchyme-like cells in SCM (sternocleidomastoid muscle). In conclusion, the present study furthermore supports maldevelopment of the

  4. The role of warmup in muscular injury prevention.

    PubMed

    Safran, M R; Garrett, W E; Seaber, A V; Glisson, R R; Ribbeck, B M

    1988-01-01

    This study is an attempt to provide biomechanical support for the athletic practice of warming up prior to an exercise task to reduce the incidence of injury. Tears in isometrically preconditioned (stimulated before stretching) muscle were compared to tears in control (nonstimulated) muscle by examining four parameters: 1) force and 2) change of length required to tear the muscle, 3) site of failure, and 4) length-tension deformation. The tibialis anterior (TA), the extensor digitorum longus (EDL), and flexor digitorum longus (EDL) muscles from both hindlimbs of rabbits comprised our experimental model. Isometrically preconditioned TA (P less than 0.001), EDL (P less than 0.005), and FDL (P less than 0.01) muscles required more force to fail than their contralateral controls. Preconditioned TA (P less than 0.05), EDL (P less than 0.001), and FDL (P less than 0.01) muscles also stretched to a greater length from rest before failing than their nonpreconditioned controls. The site of failure in all of the muscles was the musculotendinous junction; thus, the site of failure was not altered by condition. The length-tension deformation curves for all three muscle types showed that in every case the preconditioned muscles attained a lesser force at each given increase in length before failure, showing a relative increase in elasticity, although only the EDL showed a statistically significant difference. From our data, it may be inferred that physiologic warming (isometric preconditioning) is of benefit in preventing muscular injury by increasing the and length to failure and elasticity of the muscle-tendon unit.

  5. The Spinal Muscular Atrophy Disease Gene Product, Smn

    PubMed Central

    Carvalho, Teresa; Almeida, Fátima; Calapez, Alexandre; Lafarga, Miguel; Berciano, Maria T.; Carmo-Fonseca, Maria

    1999-01-01

    The spliceosomal snRNAs U1, U2, U4, and U5 are synthesized in the nucleus, exported to the cytoplasm to assemble with Sm proteins, and reimported to the nucleus as ribonucleoprotein particles. Recently, two novel proteins involved in biogenesis of small nuclear ribonucleoproteins (snRNPs) were identified, the Spinal muscular atrophy disease gene product (SMN) and its associated protein SIP1. It was previously reported that in HeLa cells, SMN and SIP1 form discrete foci located next to Cajal (coiled) bodies, the so-called “gemini of coiled bodies” or “gems.” An intriguing feature of gems is that they do not appear to contain snRNPs. Here we show that gems are present in a variable but small proportion of rapidly proliferating cells in culture. In the vast majority of cultured cells and in all primary neurons analyzed, SMN and SIP1 colocalize precisely with snRNPs in the Cajal body. The presence of SMN and SIP1 in Cajal bodies is confirmed by immunoelectron microscopy and by microinjection of antibodies that interfere with the integrity of the structure. The association of SMN with snRNPs and coilin persists during cell division, but at the end of mitosis there is a lag period between assembly of new Cajal bodies in the nucleus and detection of SMN in these structures, suggesting that SMN is targeted to preformed Cajal bodies. Finally, treatment of cells with leptomycin B (a drug that blocks export of U snRNAs to the cytoplasm and consequently import of new snRNPs into the nucleus) is shown to deplete snRNPs (but not SMN or SIP1) from the Cajal body. This suggests that snRNPs flow through the Cajal body during their biogenesis pathway. PMID:10562276

  6. Creatine supplementation improves muscular performance in older women.

    PubMed

    Gotshalk, Lincoln A; Kraemer, William J; Mendonca, Mario A G; Vingren, Jakob L; Kenny, Anne M; Spiering, Barry A; Hatfield, Disa L; Fragala, Maren S; Volek, Jeff S

    2008-01-01

    Muscle power and strength decrease with age leading to reduced independence and increased health risk from falls. Creatine supplementation can increase muscle power and strength. The purpose of this study was to examine the effects of 7 days of creatine supplementation on body composition, muscular strength, and lower-body motor functional performance in older women. Thirty 58-71 year old women performed three test sessions (T1-T3) each separated by one week. Each session consisted of one repetition maximum tests for bench press and leg press, and isometric hand-grip, tandem gait, upper-body ergometer, and lower-body ergometer tests. Following T2, subjects were assigned to a creatine monohydrate (0.3 g kg body mass(-1) for 7 days) (CR: 63.31 +/- 1.22 year, 160.00 +/- 1.58 cm, 67.11 +/- 4.38 kg) or a placebo (PL: 62.98 +/- 1.11 year, 162.25 +/- 2.09 cm, 67.84 +/- 3.90 kg) supplementation group. CR significantly (P < 0.05) increased bench press (1.7 +/- 0.4 kg), leg press (5.2 +/- 1.8 kg), body mass (0.49 +/- 0.04 kg) and fat free mass (0.52 +/- 0.05) and decreased completion time on the functional tandem gait tests from T2-T3. No significant changes were found for PL on any of the measured variables. No adverse side-effects were reported by either group. Short-term creatine supplementation resulted in an increase in strength, power, and lower-body motor functional performance in older women without any adverse side effects.

  7. Computer task performance by subjects with Duchenne muscular dystrophy

    PubMed Central

    Malheiros, Silvia Regina Pinheiro; da Silva, Talita Dias; Favero, Francis Meire; de Abreu, Luiz Carlos; Fregni, Felipe; Ribeiro, Denise Cardoso; de Mello Monteiro, Carlos Bandeira

    2016-01-01

    Aims Two specific objectives were established to quantify computer task performance among people with Duchenne muscular dystrophy (DMD). First, we compared simple computational task performance between subjects with DMD and age-matched typically developing (TD) subjects. Second, we examined correlations between the ability of subjects with DMD to learn the computational task and their motor functionality, age, and initial task performance. Method The study included 84 individuals (42 with DMD, mean age of 18±5.5 years, and 42 age-matched controls). They executed a computer maze task; all participants performed the acquisition (20 attempts) and retention (five attempts) phases, repeating the same maze. A different maze was used to verify transfer performance (five attempts). The Motor Function Measure Scale was applied, and the results were compared with maze task performance. Results In the acquisition phase, a significant decrease was found in movement time (MT) between the first and last acquisition block, but only for the DMD group. For the DMD group, MT during transfer was shorter than during the first acquisition block, indicating improvement from the first acquisition block to transfer. In addition, the TD group showed shorter MT than the DMD group across the study. Conclusion DMD participants improved their performance after practicing a computational task; however, the difference in MT was present in all attempts among DMD and control subjects. Computational task improvement was positively influenced by the initial performance of individuals with DMD. In turn, the initial performance was influenced by their distal functionality but not their age or overall functionality. PMID:26766911

  8. Compliance to Care Guidelines for Duchenne Muscular Dystrophy

    PubMed Central

    Landfeldt, Erik; Lindgren, Peter; Bell, Christopher F.; Schmitt, Claude; Guglieri, Michela; Straub, Volker

    2016-01-01

    Background International care guidelines for Duchenne muscular dystrophy (DMD) were published in 2010, but compliance in clinical practice is unknown. Objective The objective of our study was to compare real-world DMD care in Germany, Italy, the UK, and the US with the clinical recommendations. Methods DMD patients from Germany, Italy, the UK, and the US were identified through Translational Research in Europe – Assessment & Treatment of Neuromuscular Diseases (TREAT-NMD) registries and invited with a caregiver to complete a questionnaire with questions regarding DMD-related healthcare. Estimates of care were stratified by disease stage (early/late ambulatory/non-ambulatory) and compared against the care guidelines. Results A total of 770 patients (173 German, 122 Italian, 191 UK, and 284 US) completed the questionnaire. Poor compliance to guidelines of routine follow-up by neuromuscular, cardiac, and respiratory specialists, physiotherapy, and access to medical devices and aids were observed in all countries. Less than 27% (209 of 770) of patients met all absolute recommendations, ranging from 9% (11 of 122) in Italy to 37% (70 of 191) in the UK, and from 49% (76 of 155) in the early ambulatory class to 16% (33 of 205) in the late non-ambulatory class. Conclusions We show that the medical management of DMD varies substantially between Germany, Italy, the UK, and the US. Experience of real-world DMD care appears to be in poor agreement with the DMD clinical guidelines and increased compliance is urgently needed to improve treatment outcomes and enable patients to lead fulfilling, independent lives into adulthood. PMID:26870664

  9. Combined application of neuromuscular electrical stimulation and voluntary muscular contractions.

    PubMed

    Paillard, Thierry

    2008-01-01

    Electromyostimulation (EMS) and voluntary muscle contraction (VC) constitute different modes of muscle activation and induce different acute physiological effects on the neuromuscular system. Long-term application of each mode of muscle activation can produce different muscle adaptations. It seems theoretically possible to completely or partially cumulate the muscle adaptations induced by each mode of muscle activation applied separately. This work consisted of examining the literature concerning the muscle adaptations induced by long-term application of the combined technique (CT) [i.e. EMS is combined with VC - non-simultaneously] compared with VC and/or EMS alone in healthy subjects and/or athletes and in post-operative knee-injured subjects. In general, CT induced greater muscular adaptations than VC whether in sports training or rehabilitation. This efficiency would be due to the fact that CT can facilitate cumulative effects of training completely or partially induced by VC and EMS practiced alone. CT also provides a greater improvement of the performance of complex dynamic movements than VC. However, EMS cannot improve coordination between different agonistic and antagonistic muscles and thus does not facilitate learning the specific coordination of complex movements. Hence, EMS should be combined with specific sport training to generate neuromuscular adaptations, but also allow the adjustment of motor control during a voluntary movement. Likewise, in a therapeutic context, CT was particularly efficient to accelerate recovery of muscle contractility during a rehabilitation programme. Strength loss and atrophy inherent in a traumatism and/or a surgical operation would be more efficiently compensated with CT than with VC. Furthermore, CT also restored more functional abilities than VC. Finally, in a rehabilitation context, EMS is complementary to voluntary exercise because in the early phase of rehabilitation it elicits a strength increase, which is necessary

  10. Evidence for heterogeneity in facioscapulohumeral muscular dystrophy (FSHD)

    PubMed Central

    Gilbert, J. R.; Stajich, J. M.; Wall, S.; Carter, S. C.; Qiu, H.; Vance, J. M.; Stewart, C. S.; Speer, M. C.; Pufky, J.; Yamaoka, L. H.; Rozear, M.; Samson, F.; Fardeau, M.; Roses, A. D.; Pericak-Vance, M. A.

    1993-01-01

    Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive primary disease of muscle which is usually inherited as an autosomal dominant disorder. FSHD has been localized to the long arm of chromosome 4, specifically to the 4q3.5-qter region. Initially published linkage studies showed no evidence for heterogeneity in FSHD. In the present study we have examined individuals in seven FSHD families. Two-point lod scores show significant evidence for linkage for D4S163 (lod score 3.04 at recombination fraction .21) and D4S139 (lod score 3.84 at recombination fraction .20). D4S171 also gave a positive score (lod score 2.56 at recombination fraction .24). Significant evidence for heterogeneity was found for each of the three markers. Multipoint linkage analysis in this region resulted in a peak multipoint lod score of 6.47. The multipoint analysis supported the two-point studies with odds of 20:1 showing linkage and heterogeneity over linkage and homogeneity. Five of the seven families gave a posterior probability of >95% of being of the linked type, while two families appeared unlinked to this region of 4q (P < .01%). Individuals in the two unlinked families met the clinical criteria for the diagnosis of FSHD, including facial weakness, clavicular flattening, scapula winging, proximal muscle weakness, and myopathic changes on muscle biopsies without inflammatory or mitochondrial pathology. This study demonstrates genetic heterogeneity in FSHD and has important implications for both genetic counseling and the elucidation of the etiology of FSHD. PMID:8328457

  11. Dysphagia in Duchenne muscular dystrophy: practical recommendations to guide management

    PubMed Central

    Toussaint, Michel; Davidson, Zoe; Bouvoie, Veronique; Evenepoel, Nathalie; Haan, Jurn; Soudon, Philippe

    2016-01-01

    Abstract Purpose: Duchenne muscular dystrophy (DMD) is a rapidly progressive neuromuscular disorder causing weakness of the skeletal, respiratory, cardiac and oropharyngeal muscles with up to one third of young men reporting difficulty swallowing (dysphagia). Recent studies on dysphagia in DMD clarify the pathophysiology of swallowing disorders and offer new tools for its assessment but little guidance is available for its management. This paper aims to provide a step-by-step algorithm to facilitate clinical decisions regarding dysphagia management in this patient population. Methods: This algorithm is based on 30 years of clinical experience with DMD in a specialised Centre for Neuromuscular Disorders (Inkendaal Rehabilitation Hospital, Belgium) and is supported by literature where available. Results: Dysphagia can worsen the condition of ageing patients with DMD. Apart from the difficulties of chewing and oral fragmentation of the food bolus, dysphagia is rather a consequence of an impairment in the pharyngeal phase of swallowing. By contrast with central neurologic disorders, dysphagia in DMD accompanies solid rather than liquid intake. Symptoms of dysphagia may not be clinically evident; however laryngeal food penetration, accumulation of food residue in the pharynx and/or true laryngeal food aspiration may occur. The prevalence of these issues in DMD is likely underestimated. Conclusions: There is little guidance available for clinicians to manage dysphagia and improve feeding for young men with DMD. This report aims to provide a clinical algorithm to facilitate the diagnosis of dysphagia, to identify the symptoms and to propose practical recommendations to treat dysphagia in the adult DMD population.Implications for RehabilitationLittle guidance is available for the management of dysphagia in Duchenne dystrophy.Food can penetrate the vestibule, accumulate as residue or cause aspiration.We propose recommendations and an algorithm to guide management of

  12. [Clinical and spirometric alterations in patients with Duchenne muscular dystrophy].

    PubMed

    Andrada, L E; De Vito, E L

    1996-01-01

    In 36 patients with Duchenne muscular dystrophy we studied the growth pattern, the type and severity of the spirometric abnormalities, the evolution of the Motor Functional Class (MFC), the infectious complications and treatments. Their age ranged from 6 to 19 years and the MFC was from 1 to 9. Regarding height, up to 12 years we verified a slope of 5.69 +/- 0.58 cm/year (r 0.872 p < 0.001) and a posterior detention was observed. Of the 36 patients, 24 were below the percentile 5. The restrictive disorder prevailed. The forced vital capacity (FVC) expressed in % of the theoretical value showed a lineal fall with age, with a negative correlation (r 0.51, p < 0.01) of -3.5 +/- 0.83%/year. The deterioration of the MFC was marked starting from 6 years; with a slope of 0.84 +/- 0.14 points between 6 to 12 years (r 0.73 p x 0.001). Up to 14 years, the slope was 0.212 +/- 0.084 (r 0.49, p < 0.05). Patients older than 14 years had reached a greater CFM of 7; starting from this MFC a progressive fall of the VC was observed with a slope of -15.29 +/- 3.39% of CVF/CF (r 0.56, p < 0.001). Nine patients with respiratory infections were documented. Four were pneumonia and 3 of them required mechanical ventilation and died. Only 50% of the patients accepted rehabilitating treatment. Four patients accepted surgery of the alterations of the feet while the patients with deformation of the column underwent spinal stabilization.

  13. Gastrointestinal Dysfunction in Patients with Duchenne Muscular Dystrophy

    PubMed Central

    Latshang, Tsogyal D.; Bluemel, Sena; Frauenfelder, Thomas; Bloch, Konrad E.

    2016-01-01

    Background In adult patients with Duchenne muscular dystrophy (DMD) life-threatening constipation has been reported. Since gastrointestinal function in DMD has not been rigorously studied we investigated objective and subjective manifestations of gastrointestinal disturbances in DMD patients. Methods In 33 patients with DMD, age 12–41 years, eating behavior and gastrointestinal symptoms were evaluated by questionnaires. Gastric emptying half time (T1/2) and oro-cecal transit time (OCTT) were evaluated by analyzing 13CO2 exhalation curves after ingestion of 13C labeled test meals. Colonic transit time (CTT) was measured by abdominal radiography following ingestion of radiopaque markers. Results The median (quartiles) T1/2 was 187 (168, 220) minutes, the OCTT was 6.3 (5.0, 7.9) hours, both substantially longer than normal data (Goetze 2005, T1/2: 107±10; Geypens 1999, OCTT 4.3±0.1 hours). The median CTT was 60 (48, 82) hours despite extensive use of laxative measures (Meier 1995, upper limit of normal: 60 hours). T1/2 and OCTT did not correlate with symptoms evaluated by the Gastroparesis Cardinal Symptom Index (GCSI) (Spearman r = -0.3, p = 0.1; and r = -0.15, p = 0.4, respectively). CTT was not correlated with symptoms of constipation assessed by ROME III criteria (r = 0.12, p = 0.5). Conclusions DMD patients have a markedly disturbed gastrointestinal motor function. Since objective measures of impaired gastrointestinal transport are not correlated with symptoms of gastroparesis or constipation our findings suggest that measures assuring adequate intestinal transport should be taken independent of the patient’s perception in order to prevent potentially life threatening constipation, particularly in older DMD patients. PMID:27736891

  14. Dysphagia in Duchenne muscular dystrophy assessed objectively by surface electromyography.

    PubMed

    Archer, Sally K; Garrod, Rachel; Hart, Nicholas; Miller, Simon

    2013-06-01

    Objective swallowing assessment is indicated in the management of patients with Duchenne muscular dystrophy (DMD). Surface electromyography (sEMG) provides a non-invasive, objective method of quantifying muscle activity. It was hypothesised that the measurement of sEMG activity during swallowing would distinguish between preserved and disordered swallow function in DMD. This comparative study investigated the peak, duration, and relative timing of muscle activity during swallowing of four muscle groups: orbicularis oris, masseter, submental, and infrahyoid. The study included three groups of participants: Nine DMD patients with dysphagia (mean age = 21.7 ± 4.2 years), six DMD patients with preserved swallow function (21.0 ± 3.0 years), and 12 healthy controls (24.8 ± 3.1 years). Dysphagic DMD participants produced significantly higher normalised peak amplitude measurements than the healthy control group for masseter (61.77 vs. 5.07; p ≤ 0.01) and orbicularis oris muscles (71.87 vs. 26.22; p ≤ 0.05). Intrasubject variability for masseter peak amplitude was significantly greater for dysphagic DMD participants than the other groups (16.01 vs. 5.86 vs. 2.18; p ≤ 0.05). There were no differences in timing measurements between groups. Different characteristic sEMG waveforms were observed for the three groups. sEMG provides useful physiological information for the evaluation of swallowing in DMD patients, justifying further study.

  15. Growth and psychomotor development of patients with Duchenne muscular dystrophy.

    PubMed

    Sarrazin, Elisabeth; von der Hagen, Maja; Schara, Ulrike; von Au, Katja; Kaindl, Angela M

    2014-01-01

    Duchenne muscular dystrophy (DMD) is one of the most common hereditary degenerative neuromuscular diseases and caused by mutations in the dystrophin gene. The objective of the retrospective study was to describe growth and psychomotor development of patients with DMD and to detect a possible genotype-phenotype correlation. Data from 263 patients with DMD (mean age 7.1 years) treated at the Departments of Pediatric Neurology in three German University Hospitals was assessed with respect to body measurements (length, weight, body mass index BMI, head circumference OFC), motor and cognitive development as well as genotype (site of mutation). Anthropometric measures and developmental data were compared to those of a reference population and deviations were analyzed for their frequency in the cohort as well as in relation to the genotypes. Corticosteroid therapy was implemented in 29 from 263 patients. Overall 30% of the patients exhibit a short statue (length < 3rd centile) with onset early in development at 2-5 years of age, and this is even more prevalent when steroid therapy is applied (45% of patients with steroid therapy). The BMI shows a rightwards shift (68% > 50th centile) and the OFC a leftwards shift (65% < 50th centile, 5% microcephaly). Gross motor development is delayed in a third of the patients (mean age at walking 18.3 months, 30% > 18 months, 8% > 24 months). Almost half of the patients show cognitive impairment (26% learning disability, 17% intellectual disability). Although there is no strict genotype-phenotype correlation, particularly mutations in the distal part of the dystrophin gene are frequently associated with short stature and a high rate of microcephaly as well as cognitive impairment.

  16. Mothers' psychological adaptation to Duchenne/Becker muscular dystrophy.

    PubMed

    Peay, Holly L; Meiser, Bettina; Kinnett, Kathleen; Furlong, Pat; Porter, Kathryn; Tibben, Aad

    2016-05-01

    Duchenne and Becker muscular dystrophy (DBMD) cause significant emotional and care-related burden on caregivers, but no studies have evaluated predictors of positive caregiver outcomes, including disorder-specific psychological adaptation. Using a community-engaged approach focused on supporting mothers in positive aspects of caregiving, this prospective study aims to assess (i) the association between child's baseline functional status and mothers' illness perceptions, resilience, and coping self-efficacy; and (ii) predictors of mothers' psychological adaptation to caring for a child with DBMD. Biological mothers with at least one living child with DBMD completed a baseline survey (n=205) with 1-year (n=147) and 2-year (n=144) follow-up surveys. Worse child's baseline function was associated not only with increased caregiver burden and reduced maternal resilience, but also with perception of positive disease impact on the family. At two follow-ups, increased psychological adaptation to DBMD was predicted by resilience (β=0.264, P=0.001) and perceived positive impact (β=0.310, P<0.001), controlling for mother's age (β=-0.305, P<0.001) and income (β=-0.088, P=0.245). Child's functional status and caregiver burden of DBMD did not predict DBMD-specific adaptation. Though clinicians caring for families with DBMD should anticipate increased caregiver burden as the disorder progresses, interventions focused on caregiver burden are not expected to influence mothers' psychosocial adaptation. Efforts to improve mothers' well-being should focus on fostering mothers' resilience and enhancing perceptions of positive disease impact (benefit finding). Results suggest that psychosocial interventions can highlight strengths and well-being rather than burden and deficit.

  17. Postural threat influences vestibular-evoked muscular responses.

    PubMed

    Lim, Shannon B; Cleworth, Taylor W; Horslen, Brian C; Blouin, Jean-Sébastien; Inglis, J Timothy; Carpenter, Mark G

    2017-02-01

    Standing balance is significantly influenced by postural threat. While this effect has been well established, the underlying mechanisms of the effect are less understood. The involvement of the vestibular system is under current debate, and recent studies that investigated the effects of height-induced postural threat on vestibular-evoked responses provide conflicting results based on kinetic (Horslen BC, Dakin CJ, Inglis JT, Blouin JS, Carpenter MG. J Physiol 592: 3671-3685, 2014) and kinematic (Osler CJ, Tersteeg MC, Reynolds RF, Loram ID. Eur J Neurosci 38: 3239-3247, 2013) data. We examined the effect of threat of perturbation, a different form of postural threat, on coupling (cross-correlation, coherence, and gain) of the vestibulo-muscular relationship in 25 participants who maintained standing balance. In the "No-Threat" conditions, participants stood quietly on a stable surface. In the "Threat" condition, participants' balance was threatened with unpredictable mediolateral support surface tilts. Quiet standing immediately before the surface tilts was compared to an equivalent time from the No-Threat conditions. Surface EMG was recorded from bilateral trunk, hip, and leg muscles. Hip and leg muscles exhibited significant increases in peak cross-correlation amplitudes, coherence, and gain (1.23-2.66×) in the Threat condition compared with No-Threat conditions, and significant correlations were observed between threat-related changes in physiological arousal and medium-latency peak cross-correlation amplitude in medial gastrocnemius (r = 0.408) muscles. These findings show a clear threat effect on vestibular-evoked responses in muscles in the lower body, with less robust effects of threat on trunk muscles. Combined with previous work, the present results can provide insight into observed changes during balance control in threatening situations.

  18. Current Translational Research and Murine Models For Duchenne Muscular Dystrophy

    PubMed Central

    Rodrigues, Merryl; Echigoya, Yusuke; Fukada, So-ichiro; Yokota, Toshifumi

    2016-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder characterized by progressive muscle degeneration. Mutations in the DMD gene result in the absence of dystrophin, a protein required for muscle strength and stability. Currently, there is no cure for DMD. Since murine models are relatively easy to genetically manipulate, cost effective, and easily reproducible due to their short generation time, they have helped to elucidate the pathobiology of dystrophin deficiency and to assess therapies for treating DMD. Recently, several murine models have been developed by our group and others to be more representative of the human DMD mutation types and phenotypes. For instance, mdx mice on a DBA/2 genetic background, developed by Fukada et al., have lower regenerative capacity and exhibit very severe phenotype. Cmah-deficient mdx mice display an accelerated disease onset and severe cardiac phenotype due to differences in glycosylation between humans and mice. Other novel murine models include mdx52, which harbors a deletion mutation in exon 52, a hot spot region in humans, and dystrophin/utrophin double-deficient (dko), which displays a severe dystrophic phenotype due the absence of utrophin, a dystrophin homolog. This paper reviews the pathological manifestations and recent therapeutic developments in murine models of DMD such as standard mdx (C57BL/10), mdx on C57BL/6 background (C57BL/6-mdx), mdx52, dystrophin/utrophin double-deficient (dko), mdxβgeo, Dmd-null, humanized DMD (hDMD), mdx on DBA/2 background (DBA/2-mdx), Cmah-mdx, and mdx/mTRKO murine models. PMID:27854202

  19. Immunoproteasome in animal models of Duchenne muscular dystrophy.

    PubMed

    Chen, Chiao-Nan Joyce; Graber, Ted G; Bratten, Wendy M; Ferrington, Deborah A; Thompson, LaDora V

    2014-04-01

    Increased proteasome activity has been implicated in the atrophy and deterioration associated with dystrophic muscles of Duchenne muscular dystrophy (DMD). While proteasome inhibitors show promise in the attenuation of muscle degeneration, proteasome inhibition-induced toxicity was a major drawback of this therapeutic strategy. Inhibitors that selectively target the proteasome subtype that is responsible for the loss in muscle mass and quality would reduce side effects and be less toxic. This study examined proteasome activity and subtype populations, along with muscle function, morphology and damage in wild-type (WT) mice and two murine models of DMD, dystrophin-deficient (MDX) and dystrophin- and utrophin-double-knockout (DKO) mice. We found that immunoproteasome content was increased in dystrophic muscles while the total proteasome content was unchanged among the three genotypes of mice. Proteasome proteolytic activity was elevated in dystrophic muscles, especially in DKO mice. These mice also exhibited more severe muscle atrophy than either WT or MDX mice. Muscle damage and regeneration, characterized by the activity of muscle creatine kinase in the blood and the percentage of central nuclei were equally increased in dystrophic mice. Accordingly, the overall muscle function was similarly reduced in both dystrophic mice compared with WT. These data demonstrated that there was transformation of standard proteasomes to immunoproteasomes in dystrophic muscles. In addition, DKO that showed greatest increase in proteasome activities also demonstrated more severe atrophy compared with MDX and WT. These results suggest a putative role for the immunoproteasome in muscle deterioration associated with DMD and provide a potential target for therapeutic intervention.

  20. Evidence for heterogeneity in facioscapulohumeral muscular dystrophy (FSHD)

    SciTech Connect

    Gilbert, J.R.; Stajich, J.M.; Wall, S.; Carter, S.C.; Qiu, H.; Vance, J.M.; Stewart, C.S.; Speer, M.C.; Pufky, J.; Yamaoka, L.H.; Rozear, M.; Roses, A.D.; Pericak-Vance, M.A. ); Samson, F.; Fardeau, M. )

    1993-08-01

    Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive primary disease of muscle which is usually inherited as an autosomal dominant disorder. FSHD has been localized to the long arm of chromosome 4, specifically to the 4q3.5-qter region. Initially published linkage studies showed no evidence for heterogeneity in FSHD. In the present study the authors have examined individuals in seven FSHD families. Two-point lod scores show significant evidence for linkage for D4S163 (lod score 3.04 at recombination fraction .21) and D4S139 (lod score 3.84 at recombination fraction .20). D4S171 also gave a positive score (lod score 2.56 at recombination fraction .24). Significant evidence for heterogeneity was found for each of the three markers. Multipoint linkage analysis in this region resulted in a peak multipoint lod score of 6.47. The multipoint analysis supported the two-point studies with odds of 20:1 showing linkage and heterogeneity over linkage and homogeneity. Five of the seven families gave a posterior probability of >95% of being of the linked type, while two families appeared unlinked to this region of 4q (P<.01%). Individuals in the two unlinked families met the clinical criteria for the diagnosis of FSHD, including facial weakness, clavicular flattening, scapula winging, proximal muscle weakness, and myopathic changes on muscle biopsies without inflammatory or mitochondrial pathology. This study demonstrates genetic heterogeneity in FSHD and has important implications for both genetic counseling and the elucidation of the etiology of FSHD. 19 refs., 3 figs., 2 tabs.

  1. Direct interplay between two candidate genes in FSHD muscular dystrophy.

    PubMed

    Ferri, Giulia; Huichalaf, Claudia H; Caccia, Roberta; Gabellini, Davide

    2015-03-01

    Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common neuromuscular disorders. The major form of the disease (FSHD1) is linked to decrease in copy number of a 3.3-kb tandem repeated macrosatellite (D4Z4), located on chromosome 4q35. D4Z4 deletion alters chromatin structure of the locus leading to aberrant expression of nearby 4q35 genes. Given the high variability in disease onset and progression, multiple factors could contribute to the pathogenesis of FSHD. Among the FSHD candidate genes are double homeobox 4 (DUX4), encoded by the most telomeric D4Z4 unit, and FSHD region gene 1 (FRG1). DUX4 is a sequence-specific transcription factor. Here, we located putative DUX4 binding sites in the human FRG1 genomic area and we show specific DUX4 association to these regions. We found also that ectopically expressed DUX4 up-regulates the endogenous human FRG1 gene in healthy muscle cells, while DUX4 knockdown leads to a decrease in FRG1 expression in FSHD muscle cells. Moreover, DUX4 binds directly and specifically to its binding site located in the human FRG1 gene and transactivates constructs containing FRG1 genomic regions. Intriguingly, the mouse Frg1 genomic area lacks DUX4 binding sites and DUX4 is unable to activate the endogenous mouse Frg1 gene providing a possible explanation for the lack of muscle phenotype in DUX4 transgenic mice. Altogether, our results demonstrate that FRG1 is a direct DUX4 transcriptional target uncovering a novel regulatory circuit contributing to FSHD.

  2. Direct interplay between two candidate genes in FSHD muscular dystrophy

    PubMed Central

    Ferri, Giulia; Huichalaf, Claudia H.; Caccia, Roberta; Gabellini, Davide

    2015-01-01

    Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common neuromuscular disorders. The major form of the disease (FSHD1) is linked to decrease in copy number of a 3.3-kb tandem repeated macrosatellite (D4Z4), located on chromosome 4q35. D4Z4 deletion alters chromatin structure of the locus leading to aberrant expression of nearby 4q35 genes. Given the high variability in disease onset and progression, multiple factors could contribute to the pathogenesis of FSHD. Among the FSHD candidate genes are double homeobox 4 (DUX4), encoded by the most telomeric D4Z4 unit, and FSHD region gene 1 (FRG1). DUX4 is a sequence-specific transcription factor. Here, we located putative DUX4 binding sites in the human FRG1 genomic area and we show specific DUX4 association to these regions. We found also that ectopically expressed DUX4 up-regulates the endogenous human FRG1 gene in healthy muscle cells, while DUX4 knockdown leads to a decrease in FRG1 expression in FSHD muscle cells. Moreover, DUX4 binds directly and specifically to its binding site located in the human FRG1 gene and transactivates constructs containing FRG1 genomic regions. Intriguingly, the mouse Frg1 genomic area lacks DUX4 binding sites and DUX4 is unable to activate the endogenous mouse Frg1 gene providing a possible explanation for the lack of muscle phenotype in DUX4 transgenic mice. Altogether, our results demonstrate that FRG1 is a direct DUX4 transcriptional target uncovering a novel regulatory circuit contributing to FSHD. PMID:25326393

  3. Dental occlusion influences knee muscular performances in asymptomatic females.

    PubMed

    Grosdent, Stéphanie; O'Thanh, Roseline; Domken, Olivier; Lamy, Marc; Croisier, Jean-Louis

    2014-02-01

    Some authors claim that occlusal appliances can enhance athletic performance. Therefore, this study investigated the influence of dental occlusion on knee muscle strength performance. Twelve healthy female subjects (mean age, 24.1 ± 3.1 years) without temporomandibular joint dysfunction participated in this study. Isokinetic quadriceps and hamstring strength were assessed in relation to 3 randomized jaw conditions: mouth closed in maximum intercuspidation without splint, mouth closed on a balanced splint which optimized contact over the dental arch, mouth closed on a piece of resin of 1 mm which created an imbalanced occlusion. Tests were performed at 60 and 240°·s in concentric and 30°·s in eccentric exertions. Concentric performances did not show any significant difference between the 3 jaw conditions (p > 0.05). In contrast, in the eccentric trials related to quadriceps performance, significant differences (p ≤ 0.05) were observed between the resin condition and the 2 other modalities (without splint or with a balanced splint). The imbalanced occlusion created by the resin component corresponded to an average decrease of 9% in eccentric peak torque. The eccentric hamstring peak torques also showed a significant difference (p ≤ 0.05) between measurements with splint and with resin (7% decrease when occlusion was imbalanced). In conclusion, among asymptomatic females, artificial imbalanced occlusion induces immediate and significant alteration of knee eccentric muscle performances. Therefore, occlusion examination should be undertaken on a regular and frequent basis for high-level athletes. Moreover, for athletes using mouthguards, muscular performance assessments should be planned with and without the dental protection.

  4. Dental occlusion influences knee muscular performances in asymptomatic females.

    PubMed

    Grosdent, Stéphanie; O'Thanh, Roseline; Domken, Olivier; Lamy, Marc; Croisier, Jean-Louis

    2013-09-14

    Some authors claim that occlusal appliances can enhance athletic performance. Therefore this study investigated the influence of dental occlusion on knee muscle strength performance. Twelve healthy female subjects (mean age 24.1 ± 3.1 years) without temporomandibular joint dysfunction participated in this study. Isokinetic quadriceps and hamstring strength were assessed in relation to three randomized jaw conditions: mouth closed in maximum intercuspidation without splint, mouth closed on a balanced splint which optimized contact over the dental arch, mouth closed on a piece of resin of 1 mm which created an imbalanced occlusion. Tests were performed at 60°/s and 240°/s in concentric and 30°/s in eccentric exertions. Concentric performances did not show any significant difference between the 3 jaw conditions (p > 0.05). By contrast, in the eccentric trials related to quadriceps performance, significant differences (p < 0.05) were observed between the resin condition and the two other modalities (without splint or with a balanced splint). The imbalanced occlusion created by the resin component corresponded to an average decrease of 9% in eccentric peak torque. The eccentric hamstring peak torques also showed a significant difference (p < 0.05) between measurements with splint and with resin (7% decrease when occlusion was imbalanced). In conclusion, among asymptomatic females, artificial imbalanced occlusion induces immediate and significant alteration of knee eccentric muscle performances. Therefore, occlusion examination should be undertaken on a regular and frequent basis for high-level athletes. Moreover, for athletes using mouthguards, muscular performance assessments should be planned with and without the dental protection.

  5. Facioscapulohumeral Muscular Dystrophy: More Complex than it Appears

    PubMed Central

    G, Ricci; M, Zatz; R, Tupler

    2014-01-01

    Facioscapulohumeral muscular dystrophy (FSHD) has been classified as an autosomal dominant myopathy, linked to rearrangements in an array of 3.3 kb tandemly repeated DNA elements (D4Z4) located at the 4q subtelomere (4q35). For the last 20 years, the diagnosis of FSHD has been confirmed in clinical practice by the detection of one D4Z4 allele with a reduced number (≤8) of repeats at 4q35. Although wide inter- and intra-familial clinical variability was found in subjects carrying D4Z4 alleles of reduced size, this DNA testing has been considered highly sensitive and specific. However, several exceptions to this general rule have been reported. Specifically, FSHD families with asymptomatic relatives carrying D4Z4 reduced alleles, FSHD genealogies with subjects affected with other neuromuscular disorders and FSHD affected patients carrying D4Z4 alleles of normal size have been described. In order to explain these findings, it has been proposed that the reduction of D4Z4 repeats at 4q35 could be pathogenic only in certain chromosomal backgrounds, defined as “permissive” specific haplotypes. However, our most recent studies show that the current DNA signature of FSHD is a common polymorphism and that in FSHD families the risk of developing FSHD for carriers of D4Z4 reduced alleles (DRA) depends on additional factors besides the 4q35 locus. These findings highlight the necessity to re-evaluate the significance and the predictive value of DRA, not only for research but also in clinical practice. Further clinical and genetic analysis of FSHD families will be extremely important for studies aiming at dissecting the complexity of FSHD. PMID:25323867

  6. Gene therapy: a promising approach to treating spinal muscular atrophy.

    PubMed

    Mulcahy, Pádraig J; Iremonger, Kayleigh; Karyka, Evangelia; Herranz-Martín, Saúl; Shum, Ka-To; Tam, Janice Kal Van; Azzouz, Mimoun

    2014-07-01

    Spinal muscular atrophy (SMA) is a severe autosomal recessive disease caused by a genetic defect in the survival motor neuron 1 (SMN1) gene, which encodes SMN, a protein widely expressed in all eukaryotic cells. Depletion of the SMN protein causes muscle weakness and progressive loss of movement in SMA patients. The field of gene therapy has made major advances over the past decade, and gene delivery to the central nervous system (CNS) by in vivo or ex vivo techniques is a rapidly emerging field in neuroscience. Despite Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis being among the most common neurodegenerative diseases in humans and attractive targets for treatment development, their multifactorial origin and complicated genetics make them less amenable to gene therapy. Monogenic disorders resulting from modifications in a single gene, such as SMA, prove more favorable and have been at the fore of this evolution of potential gene therapies, and results to date have been promising at least. With the estimated number of monogenic diseases standing in the thousands, elucidating a therapeutic target for one could have major implications for many more. Recent progress has brought about the commercialization of the first gene therapies for diseases, such as pancreatitis in the form of Glybera, with the potential for other monogenic disease therapies to follow suit. While much research has been carried out, there are many limiting factors that can halt or impede translation of therapies from the bench to the clinic. This review will look at both recent advances and encountered impediments in terms of SMA and endeavor to highlight the promising results that may be applicable to various associated diseases and also discuss the potential to overcome present limitations.

  7. New Recommendation on Biological Materials Could Hamper Muscular Dystrophy Research

    PubMed Central

    McCormack, Pauline; Woods, Simon

    2016-01-01

    The new ‘Recommendation of the Committee of Ministers to member States on research on biological materials of human origin’, adopted in Europe in May 2016 is confusing and lacks specificity on the research use of biomaterials taken from persons not able to consent. It is possible to interpret the relevant clauses in a restrictive manner and doing so would hamper biobank research, by requiring researchers or biobank curators to examine individual records in detail, to check they are adhering to the Recommendation. This would be particularly problematic for muscular dystrophy and other rare disease research, the progress of which relies increasingly on the sharing of biomaterials and data internationally, as it will add complexity to the logistics of biomaterials and data sharing and introduce barriers for researchers preparing biomaterials for sharing. Such barriers are contradictory to EC policies on promoting and funding rare disease research and removing barriers to better care and treatment. Such policies work in concert with international progress in rare disease research, in particular the NIH’s Rare Diseases Clinical Research Network and Genetic and Rare Diseases Information Centre. The rare disease community has in recent years worked to create a common framework of harmonised approaches to enable the responsible, voluntary, and secure sharing of biomaterials and data. These efforts are supported by the European Commission in such moves as FP7 funding to advance rare disease research and the introduction of National Plans for rare disease; and are bolstered by similar efforts in the USA via the Clinical and Translational Science Awards Program and the NIH/NCATS Patient Registry developments. Introducing Recommendations from the Committee of Ministers, containing clauses which are incompatible to the efforts to advance rare disease research, seems counter-productive. PMID:28133562

  8. A method to accurately estimate the muscular torques of human wearing exoskeletons by torque sensors.

    PubMed

    Hwang, Beomsoo; Jeon, Doyoung

    2015-04-09

    In exoskeletal robots, the quantification of the user's muscular effort is important to recognize the user's motion intentions and evaluate motor abilities. In this paper, we attempt to estimate users' muscular efforts accurately using joint torque sensor which contains the measurements of dynamic effect of human body such as the inertial, Coriolis, and gravitational torques as well as torque by active muscular effort. It is important to extract the dynamic effects of the user's limb accurately from the measured torque. The user's limb dynamics are formulated and a convenient method of identifying user-specific parameters is suggested for estimating the user's muscular torque in robotic exoskeletons. Experiments were carried out on a wheelchair-integrated lower limb exoskeleton, EXOwheel, which was equipped with torque sensors in the hip and knee joints. The proposed methods were evaluated by 10 healthy participants during body weight-supported gait training. The experimental results show that the torque sensors are to estimate the muscular torque accurately in cases of relaxed and activated muscle conditions.

  9. Peripheral nerve blocks as the sole anesthetic technique in a patient with severe Duchenne muscular dystrophy.

    PubMed

    Bang, Seung Uk; Kim, Yee Suk; Kwon, Woo Jin; Lee, Sang Mook; Kim, Soo Hyang

    2016-04-01

    General anesthesia and central neuraxial blockades in patients with severe Duchenne muscular dystrophy are associated with high risks of complications, including rhabdomyolysis, malignant hyperthermia, hemodynamic instability, and postoperative mechanical ventilation. Here, we describe peripheral nerve blocks as a safe approach to anesthesia in a patient with severe Duchenne muscular dystrophy who was scheduled to undergo surgery. A 22-year-old male patient was scheduled to undergo reduction and internal fixation of a left distal femur fracture. He had been diagnosed with Duchenne muscular dystrophy at 5 years of age, and had no locomotive capability except for that of the finger flexors and toe extensors. He had developed symptoms associated with dyspnea 5 years before and required intermittent ventilation. We blocked the femoral nerve, lateral femoral cutaneous nerve, and parasacral plexus under ultrasound on the left leg. The patient underwent a successful operation using peripheral nerve blocks with no complications. In conclusion general anesthesia and central neuraxial blockades in patients with severe Duchenne muscular dystrophy are unsafe approaches to anesthesia because of hemodynamic instability and respiratory depression. Peripheral nerve blocks are the best way to reduce the risks of critical complications, and are a safe and feasible approach to anesthesia in patients with severe Duchenne muscular dystrophy.

  10. Left ventriculoplasty for dilated cardiomyopathy in Fukuyama-type muscular dystrophy.

    PubMed

    Yoda, Masataka; Tanabe, Hiroaki; Nishino, Ichizo; Suma, Hisayoshi

    2011-08-01

    A 29-year-old man was hospitalized because of heart failure causing dilated cardiomyopathy (DCM). On admission, he had elevated creatinine kinase levels (hyper CKemia) (4283IUl⁻) and false enlargement of bilateral calves. By a muscular biopsy, he was diagnosed as Fukuyama-type muscular dystrophy. Although neuromuscular diseases are often related to cardiomyopathy, reports showing a relation between cardiomyopathy and Fukuyama-type muscular dystrophy have been rare. Our group performed the partial left venticulectomy of the posterior wall and approximation of the papillary muscle, mitral valve annuloplasty, and tricuspid valve annuloplasty for DCM in the patient with Fukuyama-type muscular dystrophy, after obtaining informed consent from the patient and his family. At the 1-year follow-up examination, the neuromuscular symptoms had not progressed, and the left ventricular function was improved (left ventricular end-diastolic dimension (LVDd) 77-66 mm, left ventricular end-systolic dimension (LVDs) 73-59 mm, and ejection fraction (EF) 26-30%). This is the first case report of a left ventriculoplasty in a patient with Fukuyama-type muscular dystrophy.

  11. Intrathecal Injections in Children With Spinal Muscular Atrophy: Nusinersen Clinical Trial Experience.

    PubMed

    Haché, Manon; Swoboda, Kathryn J; Sethna, Navil; Farrow-Gillespie, Alan; Khandji, Alexander; Xia, Shuting; Bishop, Kathie M

    2016-06-01

    Nusinersen (ISIS-SMNRx or ISIS 396443) is an antisense oligonucleotide drug administered intrathecally to treat spinal muscular atrophy. We summarize lumbar puncture experience in children with spinal muscular atrophy during a phase 1 open-label study of nusinersen and its extension. During the studies, 73 lumbar punctures were performed in 28 patients 2 to 14 years of age with type 2/3 spinal muscular atrophy. No complications occurred in 50 (68%) lumbar punctures; in 23 (32%) procedures, adverse events were attributed to lumbar puncture. Most common adverse events were headache (n = 9), back pain (n = 9), and post-lumbar puncture syndrome (n = 8). In a subgroup analysis, adverse events were more frequent in older children, children with type 3 spinal muscular atrophy, and with a 21- or 22-gauge needle compared to a 24-gauge needle or smaller. Lumbar punctures were successfully performed in children with spinal muscular atrophy; lumbar puncture-related adverse event frequency was similar to that previously reported in children.

  12. 64CuCl2 PET/CT imaging of mouse muscular injury induced by electroporation

    PubMed Central

    Xie, Fang; Cai, Huawei; Peng, Fangyu

    2017-01-01

    Skeletal muscle injury is common in body injuries suffered in sports and car accidents. Development of new tracers is significant for assessing muscular injury with positron emission tomography/computed tomography (PET/CT) and monitoring repair of muscle injury in response to treatment. Copper is required for wound healing and increased copper ions were detected in the soft tissue of wound in rodents and human. Based on the recent finding of increased 64Cu uptake in the traumatic brain injury, this study aimed to explore use of 64CuCl2 as a radiotracer for molecular imaging of muscular injury using PET/CT. Focally increased 64Cu uptake by the injured muscular tissue (5.4 ± 1.2% ID/g) was detected in the C57BL/6 mice with electroporation-induced skeletal muscle injury by PET/CT after intravenous injection of 64CuCl2 as a tracer, compared to low 64Cu uptake associated with muscular inflammation induced by intramuscular injection of lipopolysaccharides (0.82 ± 0.26% ID/g, P < 0.01) or physiological 64Cu uptake of the non-injured muscular tissues (0.78 ± 0.20% ID/g, P < 0.01). The findings support further investigation of 64CuCl2 as a new radiotracer for molecular imaging of skeletal muscle injury using PET/CT. PMID:28123866

  13. Maximal strength, muscular endurance and inflammatory biomarkers in young adult men.

    PubMed

    Vaara, J P; Vasankari, T; Fogelholm, M; Häkkinen, K; Santtila, M; Kyröläinen, H

    2014-12-01

    The aim was to study associations of maximal strength and muscular endurance with inflammatory biomarkers independent of cardiorespiratory fitness in those with and without abdominal obesity. 686 young healthy men participated (25±5 years). Maximal strength was measured via isometric testing using dynamo-meters to determine maximal strength index. Muscular endurance index consisted of push-ups, sit-ups and repeated squats. An indirect cycle ergometer test until exhaustion was used to estimate maximal aerobic capacity (VO2max). Participants were stratified according to those with (>102 cm) and those without abdominal obesity (<102 cm) based on waist circumference. Inflammatory factors (C-reactive protein, interleukin-6 and tumour necrosis factor alpha) were analysed from serum samples. Maximal strength and muscular endurance were inversely associated with IL-6 in those with (β=-0.49, -0.39, respectively) (p<0.05) and in those without abdominal obesity (β=-0.08, -0.14, respectively) (p<0.05) adjusted for smoking and cardio-respiratory fitness. After adjusting for smoking and cardiorespiratory fitness, maximal strength and muscular endurance were inversely associated with CRP only in those without abdominal obesity (β=-0.11, -0.26, respectively) (p<0.05). This cross-sectional study demonstrated that muscular fitness is inversely associated with C-reactive protein and IL-6 concentrations in young adult men independent of cardiorespi-ratory fitness.

  14. A Preliminary Study of Muscular Artifact Cancellation in Single-Channel EEG

    PubMed Central

    Chen, Xun; Liu, Aiping; Peng, Hu; Ward, Rabab K.

    2014-01-01

    Electroencephalogram (EEG) recordings are often contaminated with muscular artifacts that strongly obscure the EEG signals and complicates their analysis. For the conventional case, where the EEG recordings are obtained simultaneously over many EEG channels, there exists a considerable range of methods for removing muscular artifacts. In recent years, there has been an increasing trend to use EEG information in ambulatory healthcare and related physiological signal monitoring systems. For practical reasons, a single EEG channel system must be used in these situations. Unfortunately, there exist few studies for muscular artifact cancellation in single-channel EEG recordings. To address this issue, in this preliminary study, we propose a simple, yet effective, method to achieve the muscular artifact cancellation for the single-channel EEG case. This method is a combination of the ensemble empirical mode decomposition (EEMD) and the joint blind source separation (JBSS) techniques. We also conduct a study that compares and investigates all possible single-channel solutions and demonstrate the performance of these methods using numerical simulations and real-life applications. The proposed method is shown to significantly outperform all other methods. It can successfully remove muscular artifacts without altering the underlying EEG activity. It is thus a promising tool for use in ambulatory healthcare systems. PMID:25275348

  15. Repair of an inguinoscrotal hernia in a patient with Becker muscular dystrophy

    PubMed Central

    TATULLI, F.; CARAGLIA, A.; DELCURATOLO, A.; CASSANO, S.; CHETTA, G.S.

    2016-01-01

    Introduction Inguinal hernia repairs are routinely performed as outpatient procedures in most patients, whereas a few require admission due to clinical or social peculiarities. Muscular dystrophies are inherited disorders characterized by progressive muscle wasting and weakness. In case of surgery there is no definite recommendation for either general or regional anesthesia. Case report This contribution regards a 48 y. o. male patient diagnosed with Becker Muscular Dystrophy by muscle biopsy 10 years earlier. He had a left-sided sizable inguinoscrotal hernia with repeat episodes of incarceration. An elective mesh repair with suction drainage was accomplished under selective spinal anesthesia. The post-operative course was uneventful. Discussion A few inguinal hernia repairs require admission due to peculiarities such as extensive scrotal hernias requiring suction drainage. Muscular dystrophies are inherited disorders with no cure and no two dystrophy patients are exactly alike, therefore the health issues will be different for each individual. In case of surgery there is no definite recommendation for either general or regional anesthesia. This contribution regards the successful elective mesh repair with suction drainage of a large left-sided inguino-scrotal hernia in a 48 y. o. male patient affected by Becker muscular dystrophy by selective spinal anesthesia obtained by 10 milligrams of hyperbaric bupivacaine. Conclusion Effective mesh repair with suction drainage of large inguinal hernias under spinal anesthesia can be achieved in patients affected by muscular dystrophy. PMID:28098058

  16. Brillouin spectroscopy reveals changes in muscular viscoelasticity in Drosophila POMT mutants

    NASA Astrophysics Data System (ADS)

    Meng, Zhaokai; Baker, Ryan; Panin, Vladislav M.; Yakovlev, Vladislav V.

    2015-03-01

    Muscular dystrophy (MD) is a group of muscle diseases that induce weakness in skeletal muscle and cause progressive muscle degeneration. The muscular mechanical properties (i.e., viscoelasticity), however, have not been thoroughly examined before and after MD. On the other hand, Brillouin spectroscopy (BS) provides a non-invasive approach to probing the local sound speed within a small volume. Moreover, recent advances in background-free Brillouin spectroscopy enable investigators to imaging not only transparent samples, but also turbid ones. In this study, we investigated the mechanical properties of muscles while employing Drosophila model of dystroglycanopathies, human congenital muscular dystrophies resulting from abnormal glycosylation of alphadystroglycan. Specifically, we analyzed larval abdominal muscles of Drosophila with mutations in protein Omannosyltransferase (POMT) genes. As a comparison, we have also examined muscular tissues dissected from wildtype Drosophila. The Brillouin spectra were obtained by a background free VIPA (virtually imaged phased array) spectrometer described in the previous report. As a reference, the Raman spectra were also acquired for each test. Our current results indicated that POMT defects cause changes in muscle elasticity, which suggests that muscular dystrophy conditions may be also associated with abnormalities in muscle elastic properties.

  17. Bortezomib partially improves laminin α2 chain-deficient muscular dystrophy.

    PubMed

    Körner, Zandra; Fontes-Oliveira, Cibely C; Holmberg, Johan; Carmignac, Virginie; Durbeej, Madeleine

    2014-05-01

    Congenital muscular dystrophy, caused by mutations in LAMA2 (the gene encoding laminin α2 chain), is a severe and incapacitating disease for which no therapy is yet available. We have recently demonstrated that proteasome activity is increased in laminin α2 chain-deficient muscle and that treatment with the nonpharmaceutical proteasome inhibitor MG-132 reduces muscle pathology in laminin α2 chain-deficient dy(3K)/dy(3K) mice. Here, we explore the use of the selective and therapeutic proteasome inhibitor bortezomib (currently used for treatment of relapsed multiple myeloma and mantle cell lymphoma) in dy(3K)/dy(3K) mice and in congenital muscular dystrophy type 1A muscle cells. Outcome measures included quantitative muscle morphology, gene and miRNA expression analyses, proteasome activity, motor activity, and survival. Bortezomib improved several histological hallmarks of disease, partially normalized miRNA expression (miR-1 and miR-133a), and enhanced body weight, locomotion, and survival of dy(3K)/dy(3K) mice. In addition, bortezomib reduced proteasome activity in congenital muscular dystrophy type 1A myoblasts and myotubes. These findings provide evidence that the proteasome inhibitor bortezomib partially reduces laminin α2 chain-deficient muscular dystrophy. Investigation of the clinical efficacy of bortezomib administration in congenital muscular dystrophy type 1A clinical trials may be warranted.

  18. Stem Cell Differentiation Toward the Myogenic Lineage for Muscle Tissue Regeneration: A Focus on Muscular Dystrophy.

    PubMed

    Ostrovidov, Serge; Shi, Xuetao; Sadeghian, Ramin Banan; Salehi, Sahar; Fujie, Toshinori; Bae, Hojae; Ramalingam, Murugan; Khademhosseini, Ali

    2015-12-01

    Skeletal muscle tissue engineering is one of the important ways for regenerating functionally defective muscles. Among the myopathies, the Duchenne muscular dystrophy (DMD) is a progressive disease due to mutations of the dystrophin gene leading to progressive myofiber degeneration with severe symptoms. Although current therapies in muscular dystrophy are still very challenging, important progress has been made in materials science and in cellular technologies with the use of stem cells. It is therefore useful to review these advances and the results obtained in a clinical point of view. This article focuses on the differentiation of stem cells into myoblasts, and their application in muscular dystrophy. After an overview of the different stem cells that can be induced to differentiate into the myogenic lineage, we introduce scaffolding materials used for muscular tissue engineering. We then described some widely used methods to differentiate different types of stem cell into myoblasts. We highlight recent insights obtained in therapies for muscular dystrophy. Finally, we conclude with a discussion on stem cell technology. We discussed in parallel the benefits brought by the evolution of the materials and by the expansion of cell sources which can differentiate into myoblasts. We also discussed on future challenges for clinical applications and how to accelerate the translation from the research to the clinic in the frame of DMD.

  19. Endoplasmic reticulum stress in spinal and bulbar muscular atrophy: a potential target for therapy.

    PubMed

    Montague, Karli; Malik, Bilal; Gray, Anna L; La Spada, Albert R; Hanna, Michael G; Szabadkai, Gyorgy; Greensmith, Linda

    2014-07-01

    Spinal and bulbar muscular atrophy is an X-linked degenerative motor neuron disease caused by an abnormal expansion in the polyglutamine encoding CAG repeat of the androgen receptor gene. There is evidence implicating endoplasmic reticulum stress in the development and progression of neurodegenerative disease, including polyglutamine disorders such as Huntington's disease and in motor neuron disease, where cellular stress disrupts functioning of the endoplasmic reticulum, leading to induction of the unfolded protein response. We examined whether endoplasmic reticulum stress is also involved in the pathogenesis of spinal and bulbar muscular atrophy. Spinal and bulbar muscular atrophy mice that carry 100 pathogenic polyglutamine repeats in the androgen receptor, and develop a late-onset neuromuscular phenotype with motor neuron degeneration, were studied. We observed a disturbance in endoplasmic reticulum-associated calcium homeostasis in cultured embryonic motor neurons from spinal and bulbar muscular atrophy mice, which was accompanied by increased endoplasmic reticulum stress. Furthermore, pharmacological inhibition of endoplasmic reticulum stress reduced the endoplasmic reticulum-associated cell death pathway. Examination of spinal cord motor neurons of pathogenic mice at different disease stages revealed elevated expression of markers for endoplasmic reticulum stress, confirming an increase in this stress response in vivo. Importantly, the most significant increase was detected presymptomatically, suggesting that endoplasmic reticulum stress may play an early and possibly causal role in disease pathogenesis. Our results therefore indicate that the endoplasmic reticulum stress pathway could potentially be a therapeutic target for spinal and bulbar muscular atrophy and related polyglutamine diseases.

  20. Intramuscular pressure and torque during isometric, concentric and eccentric muscular activity

    NASA Technical Reports Server (NTRS)

    Styf, J.; Ballard, R.; Aratow, M.; Crenshaw, A.; Watenpaugh, D.; Hargens, A. R.

    1995-01-01

    Intramuscular pressures, electromyography (EMG) and torque generation during isometric, concentric and eccentric maximal isokinetic muscle activity were recorded in 10 healthy volunteers. Pressure and EMG activity were continuously and simultaneously measured side by side in the tibialis anterior and soleus muscles. Ankle joint torque and position were monitored continuously by an isokinetic dynamometer during plantar flexion and dorsiflexion of the foot. The increased force generation during eccentric muscular activity, compared with other muscular activity, was not accompanied by higher intramuscular pressure. Thus, this study demonstrated that eccentric muscular activity generated higher torque values for each increment of intramuscular pressure. Intramuscular pressures during antagonistic co-activation were significantly higher in the tibilis anterior muscle (42-46% of maximal agonistic activity) compared with the soleus muscle (12-29% of maximal agonistic activity) and was largely due to active recruitment of muscle fibers. In summary, eccentric muscular activity creates higher torque values with no additional increase of the intramuscular pressure compared with concentric and isometric muscular activity.

  1. Age-related thoracic radiographic changes in golden and labrador retriever muscular dystrophy.

    PubMed

    Bedu, Anne-Sophie; Labruyère, Julien J; Thibaud, Jean Laurent; Barthélémy, Inès; Leperlier, Dimitri; Saunders, Jimmy H; Blot, Stéphane

    2012-01-01

    Golden retriever and Labrador retriever muscular dystrophy are inherited progressive degenerative myopathies that are used as models of Duchenne muscular dystrophy in man. Thoracic lesions were reported to be the most consistent radiographic finding in golden retriever dogs in a study where radiographs were performed at a single-time point. Muscular dystrophy worsens clinically over time and longitudinal studies in dogs are lacking. Thus our goal was to describe the thoracic abnormalities of golden retriever and Labrador retriever dogs, to determine the timing of first expression and their evolution with time. To this purpose, we retrospectively reviewed 390 monthly radiographic studies of 38 golden retrievers and six Labrador retrievers with muscular dystrophy. The same thoracic lesions were found in both golden and Labrador retrievers. They included, in decreasing frequency, flattened and/or scalloped diaphragmatic shape (43/44), pulmonary hyperinflation (34/44), hiatal hernia (34/44), cranial pectus excavatum (23/44), bronchopneumonia (22/44), and megaesophagus (14/44). The last three lesions were not reported in a previous radiographic study in golden retriever dogs. In all but two dogs the thoracic changes were detected between 4 and 10 months and were persistent or worsened over time. Clinically, muscular dystrophy should be included in the differential diagnosis of dogs with a combination of these thoracic radiographic findings.

  2. [Altered expression of myostatin gene in the progressive muscular dystrophy patients].

    PubMed

    Zhang, Yong; Chen, Yan; Chen, Jia-Wei; Zhu, Da-Hai

    2005-08-01

    Progressive muscular dystrophy is a group of inherited disorders characterized by progressive skeletal muscle wasting and weakness, which is not of neurogenic origin. Myostatin, a new member of the TGF-beta super-family, is a negative regulator of skeletal muscle growth. To investigate the possible involvement of myostatin in the development of progressive muscular dystrophy, we cloned and sequenced myostatin cDNAs from the progressive muscular dystrophy patients by RT-PCR. Levels of myostatin mRNA and protein in the patients were analyzed by semi-quantitative RT-PCR and Western blot,respectively. We did not find any mutations in the myostatin cDNA sequences from the progressive muscular dystrophy patients in this study. However, we found that the levels of myostatin transcripts were reduced in some patients and the processing and maturation of myostatin protein were inhibited in some patients. Our data demonstrated that the pathogenesis of some types or subtypes of progressive muscular dystrophy is probably associated with the altered myostatin expression and the processing inhibition of myostatin protein.

  3. The Dutch patients' perspective on oculopharyngeal muscular dystrophy: A questionnaire study on fatigue, pain and impairments.

    PubMed

    van der Sluijs, Barbara M; Knoop, Hans; Bleijenberg, Gijs; van Engelen, Baziel G M; Voermans, Nicol C

    2016-03-01

    Research on oculopharyngeal muscular dystrophy focuses mainly on genetic and pathophysiological aspects. Clinically, oculopharyngeal muscular dystrophy is often considered as a disease with a relatively mild initial disease course with no or only mild functional disabilities. However the occurrence of fatigue, pain and functional impairments other than dysphagia has never been studied systematically. The aim of this study is therefore to assess the prevalence of fatigue, pain, and functional limitations, and the social participation and psychological well-being of oculopharyngeal muscular dystrophy patients. We performed a questionnaire study on fatigue, pain, functional impairments, social participation and psychological distress in 35 genetically confirmed oculopharyngeal muscular dystrophy patients with an average disease duration of 11.6 years. We showed that 19 (54%) of the patients experienced severe fatigue and also 19 (54%) experienced pain. Limitations in daily life activities and social participation were detected in 33 (94%) of the patients. Many patients reported pelvic girdle weakness and limitations in ambulation. Fatigue severity was related to functional impairments, while pain and disease duration were not. Psychological distress was not different from healthy adults. In conclusion, fatigue and pain are present among approximately half of the patients, and almost all patients are impaired in daily life activities, social participation and ambulation. These data should be taken into account in symptomatic management of oculopharyngeal muscular dystrophy.

  4. Real-time control system verification for ELT AO systems

    NASA Astrophysics Data System (ADS)

    Basden, Alastair; Myers, Richard; Morris, Tim; Bharmal, Nazim; Bitenc, Urban; Dipper, Nigel; Reeves, Andrew; Gendron, Eric; Rousset, Gérard; Hubert, Zoltan; Vidal, Fabrice; Matin, Olivier; Gratadour, Damien; Chemla, Fanny

    2013-12-01

    ELT AO systems have demanding computational requirements for real-timecontrol. These systems are required to be fully tested and robustbefore commissioning so that valuable on-sky time is not wasted. Inthis talk I will report recent work at Durham on our ELT AO real-timecontrol system, algorithms that we use to improve robustness, anddevelopment of an end-to-end testing environment that will allow fulltesting of real-time control systems, including both Monte-Carlosimulation and hardware approaches. The talk will include experiencegained with CANARY, how the robustness of this system has beenimproved, and our experience operating with four laser guide stars. Workcarried out in this area on the DRAGON test-bench will also bedescribed.

  5. High-Resolution Imaging of Asteroids/Satellites with AO

    NASA Astrophysics Data System (ADS)

    Merline, William

    2012-02-01

    We propose to make high-resolution observations of asteroids using AO, to measure size, shape, and pole position (spin vectors), and/or to search for satellites. We have demonstrated that AO imaging allows determination of the pole/dimensions in 1 or 2 nights on a single target, rather than the years of observations with lightcurve inversion techniques that only yield poles and axial ratios, not true dimensions. Our new technique (KOALA) combines AO imaging with lightcurve and occultation data for optimum size/shape determinations. We request that LGS be available for faint targets, but using NGS AO, we will measure several large and intermediate asteroids that are favorably placed in spring/summer of 2012 for size/shape/pole. Accurately determining the volume from the often-irregular shape allows us to derive densities to much greater precision in cases where the mass is known, e.g., from the presence of a satellite. We will search several d! ozen asteroids for the presence of satellites, particularly in under-studied populations, particularly NEOs (we have recently achieved the first-ever optical image of an NEO binary [Merline et al. 2008b, IAUC 8977]). Satellites provide a real-life lab for testing collisional models. We will search for satellites around special objects at the request of lightcurve observers, and we will make a search for debris in the vicinity of Pluto, in support of the New Horizons mission. Our shape/size work requires observations over most of a full rotation period (typically several hours).

  6. LDEF results for polymer matrix composite experiment AO 180

    NASA Technical Reports Server (NTRS)

    Tennyson, R. C.

    1992-01-01

    This report represents a summary of the results obtained to-date on a polymer matrix composite experiment (AO 180) located at station D-12, about 82 deg off the 'ram' direction. Different material systems comprised of graphite, boron, and aramid (Kevlar) fiber reinforcements were studied. Although previous results were presented on in-situ thermal-vacuum cycling effects, particularly dimensional changes associated with outgassing, additional comparative data will be shown from ground-based tests on control and flight samples. The system employed was fully automated for thermal-vacuum cycling using a laser interferometer for monitoring displacements. Erosion of all three classes of materials due to atomic oxygen (AO) will also be discussed, including angle of incidence effects. Data from this experiment will be compared to published results for similar materials in other LDEF experiments. Composite materials' erosion yields will be presented on an AO design nomogram useful for estimating total material loss for given exposure conditions in low Earth orbit (LEO). Optical properties of these materials will also be compared with control samples. A survey of the damage caused by micrometeoroids/debris impacts will be addressed as they relate to polymer matrix composites. Correlations between hole size and damage pattern will be given. Reference to a new nomogram for estimating the number distribution of micrometeoroid/debris impacts for a given space structure as a function of time in LEO will be addressed based on LDEF data.

  7. Single-shot retinal imaging with AO spectral OCT

    NASA Astrophysics Data System (ADS)

    Zhang, Yan; Rha, Jungtae; Jonnal, Ravi S.; Miller, Donald T.

    2005-04-01

    We demonstrate for the first time an adaptive optics (AO) spectral OCT retina camera that acquires with unprecedented 3D resolution (2.9 μm lateral; 5.5 μm axial) single shot B-scans of the living human retina. The camera centers on a Michelson interferometer that consists of a superluminescent diode for line illuminating the subject's retinal; voice coil translator for controlling the optical path length of the reference channel; and an imaging spectrometer that is cascaded with a 12-bit area CCD array. The imaging spectrometer was designed with negligible off-axis aberrations and was constructed from stock optical components. AO was integrated into the detector channel of the interferometer and dynamically compensated for most of the ocular aberration across a 6 mm pupil. Short bursts of B-scans, with 100 Ascans each, were successfully acquired at 1 msec intervals. Camera sensitivity was found sufficient to detect reflections from all major retinal layers. Individual outer segments of photoreceptors at different retinal eccentricities were observed in vivo. Periodicity of the outer segments matched cone spacing as measured from AO flood illuminated images of the same patches of retina.

  8. AO Distal Radius Fracture Classification: Global Perspective on Observer Agreement.

    PubMed

    Jayakumar, Prakash; Teunis, Teun; Giménez, Beatriz Bravo; Verstreken, Frederik; Di Mascio, Livio; Jupiter, Jesse B

    2017-02-01

    Background The primary objective of this study was to test interobserver reliability when classifying fractures by consensus by AO types and groups among a large international group of surgeons. Secondarily, we assessed the difference in inter- and intraobserver agreement of the AO classification in relation to geographical location, level of training, and subspecialty. Methods A randomized set of radiographic and computed tomographic images from a consecutive series of 96 distal radius fractures (DRFs), treated between October 2010 and April 2013, was classified using an electronic web-based portal by an invited group of participants on two occasions. Results Interobserver reliability was substantial when classifying AO type A fractures but fair and moderate for type B and C fractures, respectively. No difference was observed by location, except for an apparent difference between participants from India and Australia classifying type B fractures. No statistically significant associations were observed comparing interobserver agreement by level of training and no differences were shown comparing subspecialties. Intra-rater reproducibility was "substantial" for fracture types and "fair" for fracture groups with no difference accounting for location, training level, or specialty. Conclusion Improved definition of reliability and reproducibility of this classification may be achieved using large international groups of raters, empowering decision making on which system to utilize. Level of Evidence Level III.

  9. [7 MHz real-time sonography of the skeletal musculature in Duchenne muscular dystrophy].

    PubMed

    Forst, R; Casser, H R

    1985-12-01

    The lumbar paravertebral musculature, the M. quadriceps femoris and M. triceps surae of boys suffering from Duchenne's muscular dystrophy of different clinical progression, were examined via sonography. The sonographic incisions were made at fixed levels. The sonographic findings were compared with those of healthy boys. The sonographic findings showed - depending on the clinical stage of Duchenne's muscular dystrophy - typical reflex patterns of different intensity determined by lipomatosis and fibrosis of the skeletal musculature, correlating with the clinical stage, and hence musclesonography is an important diagnostic element in the observation of the course and in therapy planning in Duchenne's muscular dystrophy. The 7-MHz transducer has an advantage over the low-frequency transducers mostly in use, because the image quality is substantially superior.

  10. Exercise dependence and the drive for muscularity in male bodybuilders, power lifters, and fitness lifters.

    PubMed

    Hale, Bruce D; Roth, Andrew D; DeLong, Ryan E; Briggs, Michael S

    2010-06-01

    Researchers have hypothesized differences in exercise dependence and drive for muscularity between bodybuilders and power lifters, while others have not found the predicted differences. This study assessed 146 weight lifters (bodybuilders, n=59; power lifters, n=47; fitness lifters, n=40) on the Exercise Dependence Scale, Bodybuilding Dependence Scale, and the Drive for Muscularity Scale. Results showed that bodybuilders and power lifters were significantly higher than fitness lifters on EDS Total, 7 EDS scales, and the 3 BDS scales. In contrast, power lifters were found to be significantly higher on DMS Total and DMS Behavior scales than bodybuilders. The regression results suggest that exercise dependence may be directly related to the drive for muscularity.

  11. Sexuality and the drive for muscularity: evidence of associations among British men.

    PubMed

    Swami, Viren; Diwell, Rachel; McCreary, Donald R

    2014-09-01

    Previous studies have documented associations between sexuality and body image, but the directionality of this association is unclear among men. This study examined whether men's drive for muscularity can be considered a correlate of their sexuality. A community-based sample of 292 heterosexual men from London, UK, completed a survey consisting of measures of drive for muscularity, sociosexuality, sexual assertiveness, sexual esteem, and sexual sensation seeking. A multiple regression analysis showed that greater drive for muscularity was predicted by more unrestricted sociosexuality (i.e., a greater proclivity for short-term, transient relationships), greater sexual sensation seeking, and greater sexual assertiveness, once the effects of participant age and body mass index had been accounted for. Possible avenues for intervention based on a sex-positive approach are discussed in conclusion.

  12. Temporalis muscle hypertrophy and reduced skull eccentricity in Duchenne muscular dystrophy.

    PubMed

    Straathof, C S M; Doorenweerd, N; Wokke, B H A; Dumas, E M; van den Bergen, J C; van Buchem, M A; Hendriksen, J G M; Verschuuren, J J G M; Kan, H E

    2014-10-01

    Muscle hypertrophy and muscle weakness are well known in Duchenne muscular dystrophy. Decreased muscle force can have secondary effects on skeletal growth and development such as facial and dental morphology changes. In this study, we quantified temporal muscle thickness, circumference, and eccentricity of the skull and the head on T1-weighted magnetic resonance imaging (MRI) scans of the head of 15 Duchenne muscular dystrophy patients and 15 controls. Average temporal muscle thickness was significantly increased in patients (12.9 ± 5.2 mm) compared to controls (6.8 ± 1.4 mm) (P < .0001), whereas the shape of the skull was significantly rounder compared to controls. Temporal muscle thickness and skull eccentricity were significantly negatively correlated in patients, and positively in controls. Hypertrophy of the temporal muscles and changes in skull eccentricity appear to occur early in the course of Duchenne muscular dystrophy. Further studies in younger patients are needed to confirm a causal relationship.

  13. Botulinum toxin type a in the treatment of children with congenital muscular torticollis.

    PubMed

    Oleszek, Joyce L; Chang, Nicki; Apkon, Susan D; Wilson, Pamela E

    2005-10-01

    This is a retrospective case series describing the use of botulinum toxin type A in the treatment of children with congenital muscular torticollis who fail to progress with conservative management. A total of 27 children with congenital muscular torticollis, 6-18 mos of age, received 30 botulinum toxin type A injections into their sternocleidomastoid or upper trapezius muscle, or both, at a pediatric tertiary care center between 1995 and 2001. Three children received repeat injections. Twenty of 27 children (74%) had improved cervical rotation or head tilt after the injections, and 2 of 27 (7%) experienced transient adverse events, specifically, mild dysphagia and neck weakness. This series suggests that botulinum toxin type A may be a safe and effective treatment option for children with congenital muscular torticollis who are unresponsive to a traditional regimen of physical therapy and a home program. A prospective, randomized controlled trial is necessary to definitively assess the role of botulinum toxin type A in this population.

  14. Does increased muscular tension along the torso disturb postural equilibrium more when it is asymmetrical?

    PubMed

    Hamaoui, Alain; Le Bozec, Serge

    2014-01-01

    The aim of this study was to determine whether increased muscular tension disturbs postural equilibrium more when it is asymmetrical. Ten healthy male subjects underwent a posturographic examination associated with an original uni and bilateral compressive load paradigm designed to set the active muscular tension at different controlled levels along each side of the torso. Respiratory kinematics were recorded by means of two sensing belts. Two electromyographic pre-tests were used to map out the main motor muscles of the task and to quantify the level of asymmetry induced by unilateral loads. The posturographic examination revealed that the mean deviation of the CP along the medial-lateral axis was significantly greater in unilateral than in bilateral compressive loads. It was suggested that increased muscular tension along the torso induces a more disturbing effect on posture when it is asymmetrical.

  15. The muscular force transmission system: role of the intramuscular connective tissue.

    PubMed

    Turrina, Andrea; Martínez-González, Miguel Antonio; Stecco, Carla

    2013-01-01

    The objective of this review is to analyze in detail the microscopic structure and relations among muscular fibers, endomysium, perimysium, epimysium and deep fasciae. In particular, the multilayer organization and the collagen fiber orientation of these elements are reported. The endomysium, perimysium, epimysium and deep fasciae have not just a role of containment, limiting the expansion of the muscle with the disposition in concentric layers of the collagen tissue, but are fundamental elements for the transmission of muscular force, each one with a specific role. From this review it appears that the muscular fibers should not be studied as isolated elements, but as a complex inseparable from their fibrous components. The force expressed by a muscle depends not only on its anatomical structure, but also the angle at which its fibers are attached to the intramuscular connective tissue and the relation with the epimysium and deep fasciae.

  16. Histopathological Evaluation of Skeletal Muscle with Specific Reference to Mouse Models of Muscular Dystrophy.

    PubMed

    Terry, Rebecca L; Wells, Dominic J

    2016-12-01

    The muscular dystrophies are a diverse group of degenerative diseases for which many mouse models are available. These models are frequently used to assess potential therapeutic interventions and histological evaluation of multiple muscles is an important part of this assessment. Histological evaluation is especially useful when combined with tests of muscle function. This unit describes a protocol for necropsy, processing, cryosectioning, and histopathological evaluation of murine skeletal muscles, which is applicable to both models of muscular dystrophy and other neuromuscular conditions. Key histopathological features of dystrophic muscle are discussed using the mdx mouse (a model of Duchenne muscular dystrophy) as an example. Optimal handling during dissection, processing and sectioning is vital to avoid artifacts that can confound or prevent future analyses. Muscles carefully processed using this protocol are suitable for further evaluation using immunohistochemistry, immunofluorescence, special histochemical stains, and immuoblotting. © 2016 by John Wiley & Sons, Inc.

  17. Enhanced autophagy as a potential mechanism for the improved physiological function by simvastatin in muscular dystrophy.

    PubMed

    Whitehead, Nicholas P

    2016-01-01

    Autophagy has recently emerged as an important cellular process for the maintenance of skeletal muscle health and function. Excessive autophagy can trigger muscle catabolism, leading to atrophy. In contrast, reduced autophagic flux is a characteristic of several muscle diseases, including Duchenne muscular dystrophy, the most common and severe inherited muscle disorder. Recent evidence demonstrates that enhanced reactive oxygen species (ROS) production by CYBB/NOX2 impairs autophagy in muscles from the dmd/mdx mouse, a genetic model of Duchenne muscular dystrophy. Statins decrease CYBB/NOX2 expression and activity and stimulate autophagy in skeletal muscle. Therefore, we treated dmd/mdx mice with simvastatin and showed decreased CYBB/NOX2-mediated oxidative stress and enhanced autophagy induction. This was accompanied by reduced muscle damage, inflammation and fibrosis, and increased muscle force production. Our data suggest that increased autophagy may be a potential mechanism by which simvastatin improves skeletal muscle health and function in muscular dystrophy.

  18. Distribution patterns of the muscular branch of the median nerve in the thenar region.

    PubMed Central

    Olave, E; Prates, J C; Del Sol, M; Sarmento, A; Gabrielli, C

    1995-01-01

    Studies on the distribution patterns of the muscular branch of the median nerve to the thenar muscles are scarce. Available accounts give only general descriptions. To establish the distribution pattern more precisely, we dissected 60 palmar regions from 30 cadavers of adult individuals, ranging in age from 23 to 77 y. The distribution pattern of the muscular branch was classified into 3 types. In 50% of subjects there were branches to the superficial head of flexor pollicis brevis (FPB), abductor pollicis brevis (APB) and opponens pollicis (OP) (type I). In 40% there were branches only to APB and OP (type II). In the remainder (type III) the muscular branch provided independent branches to APB, OP and FPB, to APB and OP, or to APB and FPB, after dividing precociously. Types I and II were further subdivided according to the site, direction and number of the individual branches. Images Fig. 4 Fig. 5 Fig. 6 PMID:7649846

  19. De novo and inherited deletions of the 5q13 region in spinal muscular atrophies

    SciTech Connect

    Melki, J.; Lefebvre, S.; Burglen, L.; Burlet, P.; Clermont, O.; Reboullet, S.; Benichou, B.; Zeviani, M. ); Millasseau, P. ); Le Paslier, D. )

    1994-06-03

    Spinal muscular atrophies (SMAs) represent the second most common fatal autosomal recessive disorder after cystic fibrosis. Childhood spinal muscular atrophies are divided into severe (type I) and mild forms (types II and III). By a combination of genetic and physical mapping, a yeast artificial chromosome contig of the 5q13 region spanning the disease locus was constructed that showed the presence of low copy repeats in this region. Allele segregation was analyzed at the closest genetic loci detected by markers C212 and C272 in 201 SMA families. Inherited and de novo deletions were observed in nine unrelated SMA patients. Moreover, deletions were strongly suggested in at least 18 percent of SMA type I patients by the observation of marked heterozygosity deficiency for the loci studied. These results indicate that deletion events are statistically associated with the severe form of spinal muscular atrophy. 25 refs., 5 figs.

  20. Do representations of male muscularity differ in men's and women's magazines?

    PubMed

    Frederick, David A; Fessler, Daniel M T; Haselton, Martie G

    2005-03-01

    Men overestimate the degree of muscularity that is attractive to women, and women overestimate the degree of thinness that is most attractive to men. Consistent with the thesis that sociocultural input influences such body type preferences and beliefs, we postulated that magazines aimed at a male audience would portray a more muscular male body ideal than would magazines aimed at a female audience. Systematic comparison of popular magazines (Cosmopolitan, Men's Health, Men's Fitness, and Muscle & Fitness) revealed that the ideal male body marketed to men is more muscular than the ideal male body marketed to women. We introduce the Physical Trait Overvaluation Hypothesis, which proposes that gender-specific media fuel emphasis on certain body parts in within-gender prestige competitions. The resulting competitive escalation creates a disconnect between the preferences of one gender and the personal aspirations of the other.

  1. The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy.

    PubMed

    Marshall, Jamie L; Kwok, Yukwah; McMorran, Brian J; Baum, Linda G; Crosbie-Watson, Rachelle H

    2013-09-01

    Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein-replacement therapy offers a promising approach for the treatment of muscular dystrophy. Recently, we demonstrated that sarcospan facilitates protein-protein interactions amongst the adhesion complexes and is an important potential therapeutic target. Here, we review current protein-replacement strategies, discuss the potential benefits of sarcospan expression, and identify important experiments that must be addressed for sarcospan to move to the clinic.

  2. CINRG randomized controlled trial of creatine and glutamine in Duchenne muscular dystrophy.

    PubMed

    Escolar, Diana M; Buyse, Gunnar; Henricson, Erik; Leshner, Robert; Florence, Julaine; Mayhew, Jill; Tesi-Rocha, Carolina; Gorni, Ksenija; Pasquali, Livia; Patel, Kantilal M; McCarter, Robert; Huang, Jennifer; Mayhew, Thomas; Bertorini, Tulio; Carlo, Jose; Connolly, Anne M; Clemens, Paula R; Goemans, Nathalie; Iannaccone, Susan T; Igarashi, Masanori; Nevo, Yoram; Pestronk, Alan; Subramony, S H; Vedanarayanan, V V; Wessel, Henry

    2005-07-01

    We tested the efficacy and safety of glutamine (0.6 gm/kg/day) and creatine (5 gm/day) in 50 ambulant boys with Duchenne muscular dystrophy in a 6-month, double-blind, placebo-controlled clinical trial. Drug efficacy was tested by measuring muscle strength manually (34 muscle groups) and quantitatively (10 muscle groups). Timed functional tests, functional parameters, and pulmonary function tests were secondary outcome measures. Although there was no statistically significant effect of either therapy based on manual and quantitative measurements of muscle strength, a disease-modifying effect of creatine in older Duchenne muscular dystrophy and creatine and glutamine in younger Duchenne muscular dystrophy cannot be excluded. Creatine and glutamine were well tolerated.

  3. SIMS chemical and isotopic analysis of impact features from LDEF experiments AO187-1 and AO187-2

    NASA Technical Reports Server (NTRS)

    Stadermann, Frank J.; Amari, Sachiko; Foote, John; Swan, Pat; Walker, Robert M.; Zinner, Ernst

    1995-01-01

    Previous secondary ion mass spectrometry (SIMS) studies of extended impact features from LDEF capture cell experiment AO187-2 showed that it is possible to distinguish natural and man-made particle impacts based on the chemical composition of projectile residues. The same measurement technique has now been applied to specially prepared gold target impacts from experiment AO187-1 in order to identify the origins of projectiles that left deposits too thin to be analyzed by conventional energy-dispersive x-ray (EDX) spectroscopy. The results indicate that SIMS may be the method of choice for the analysis of impact deposits on a variety of sample surfaces. SIMS was also used to determine the isotopic compositions of impact residues from several natural projectiles. Within the precision of the measurements all analyzed residues show isotopically normal compositions.

  4. Impaired Muscle Mitochondrial Biogenesis and Myogenesis in Spinal Muscular Atrophy

    PubMed Central

    Ripolone, Michela; Ronchi, Dario; Violano, Raffaella; Vallejo, Dionis; Fagiolari, Gigliola; Barca, Emanuele; Lucchini, Valeria; Colombo, Irene; Villa, Luisa; Berardinelli, Angela; Balottin, Umberto; Morandi, Lucia; Mora, Marina; Bordoni, Andreina; Fortunato, Francesco; Corti, Stefania; Parisi, Daniela; Toscano, Antonio; Sciacco, Monica; DiMauro, Salvatore; Comi, Giacomo P.; Moggio, Maurizio

    2016-01-01

    IMPORTANCE The important depletion of mitochondrial DNA (mtDNA) and the general depression of mitochondrial respiratory chain complex levels (including complex II) have been confirmed, implying an increasing paucity of mitochondria in the muscle from patients with types I, II, and III spinal muscular atrophy (SMA-I, -II, and -III, respectively). OBJECTIVE To investigate mitochondrial dysfunction in a large series of muscle biopsy samples from patients with SMA. DESIGN, SETTING, AND PARTICIPANTS We studied quadriceps muscle samples from 24 patients with genetically documented SMA and paraspinal muscle samples from 3 patients with SMA-II undergoing surgery for scoliosis correction. Postmortem muscle samples were obtained from 1 additional patient. Age-matched controls consisted of muscle biopsy specimens from healthy children aged 1 to 3 years who had undergone analysis for suspected myopathy. Analyses were performed at the Neuromuscular Unit, Istituto di Ricovero e Cura a Carattere Scientifico Foundation Ca’ Granda Ospedale Maggiore Policlinico-Milano, from April 2011 through January 2015. EXPOSURES We used histochemical, biochemical, and molecular techniques to examine the muscle samples. MAIN OUTCOMES AND MEASURES Respiratory chain activity and mitochondrial content. RESULTS Results of histochemical analysis revealed that cytochrome-c oxidase (COX) deficiency was more evident in muscle samples from patients with SMA-I and SMA-II. Residual activities for complexes I, II, and IV in muscles from patients with SMA-I were 41%, 27%, and 30%, respectively, compared with control samples (P < .005). Muscle mtDNA content and cytrate synthase activity were also reduced in all 3 SMA types (P < .05). We linked these alterations to downregulation of peroxisome proliferator–activated receptor coactivator 1α, the transcriptional activators nuclear respiratory factor 1 and nuclear respiratory factor 2, mitochondrial transcription factor A, and their downstream targets

  5. Analysing regenerative potential in zebrafish models of congenital muscular dystrophy.

    PubMed

    Wood, A J; Currie, P D

    2014-11-01

    The congenital muscular dystrophies (CMDs) are a clinically and genetically heterogeneous group of muscle disorders. Clinically hypotonia is present from birth, with progressive muscle weakness and wasting through development. For the most part, CMDs can mechanistically be attributed to failure of basement membrane protein laminin-α2 sufficiently binding with correctly glycosylated α-dystroglycan. The majority of CMDs therefore arise as the result of either a deficiency of laminin-α2 (MDC1A) or hypoglycosylation of α-dystroglycan (dystroglycanopathy). Here we consider whether by filling a regenerative medicine niche, the zebrafish model can address the present challenge of delivering novel therapeutic solutions for CMD. In the first instance the readiness and appropriateness of the zebrafish as a model organism for pioneering regenerative medicine therapies in CMD is analysed, in particular for MDC1A and the dystroglycanopathies. Despite the recent rapid progress made in gene editing technology, these approaches have yet to yield any novel zebrafish models of CMD. Currently the most genetically relevant zebrafish models to the field of CMD, have all been created by N-ethyl-N-nitrosourea (ENU) mutagenesis. Once genetically relevant models have been established the zebrafish has several important facets for investigating the mechanistic cause of CMD, including rapid ex vivo development, optical transparency up to the larval stages of development and relative ease in creating transgenic reporter lines. Together, these tools are well suited for use in live-imaging studies such as in vivo modelling of muscle fibre detachment. Secondly, the zebrafish's contribution to progress in effective treatment of CMD was analysed. Two approaches were identified in which zebrafish could potentially contribute to effective therapies. The first hinges on the augmentation of functional redundancy within the system, such as upregulating alternative laminin chains in the candyfloss

  6. In Vivo Dynamic Deformation of Articular Cartilage in Intact Joints Loaded by Controlled Muscular Contractions

    PubMed Central

    Abusara, Ziad; Von Kossel, Markus; Herzog, Walter

    2016-01-01

    When synovial joints are loaded, the articular cartilage and the cells residing in it deform. Cartilage deformation has been related to structural tissue damage, and cell deformation has been associated with cell signalling and corresponding anabolic and catabolic responses. Despite the acknowledged importance of cartilage and cell deformation, there are no dynamic data on these measures from joints of live animals using muscular load application. Research in this area has typically been done using confined and unconfined loading configurations and indentation testing. These loading conditions can be well controlled and allow for accurate measurements of cartilage and cell deformations, but they have little to do with the contact mechanics occurring in a joint where non-congruent cartilage surfaces with different material and functional properties are pressed against each other by muscular forces. The aim of this study was to measure in vivo, real time articular cartilage deformations for precisely controlled static and dynamic muscular loading conditions in the knees of mice. Fifty and 80% of the maximal knee extensor muscular force (equivalent to approximately 0.4N and 0.6N) produced average peak articular cartilage strains of 10.5±1.0% and 18.3±1.3% (Mean ± SD), respectively, during 8s contractions. A sequence of 15 repeat, isometric muscular contractions (0.5s on, 3.5s off) of 50% and 80% of maximal muscular force produced cartilage strains of 3.0±1.1% and 9.6±1.5% (Mean ± SD) on the femoral condyles of the mouse knee. Cartilage thickness recovery following mechanical compression was highly viscoelastic and took almost 50s following force removal in the static tests. PMID:26807930

  7. Overexpression of Latent TGFβ Binding Protein 4 in Muscle Ameliorates Muscular Dystrophy through Myostatin and TGFβ

    PubMed Central

    Gardner, Brandon B.; Gao, Quan Q.; Hadhazy, Michele; Vo, Andy H.; Wren, Lisa; Molkentin, Jeffery D.; McNally, Elizabeth M.

    2016-01-01

    Latent TGFβ binding proteins (LTBPs) regulate the extracellular availability of latent TGFβ. LTBP4 was identified as a genetic modifier of muscular dystrophy in mice and humans. An in-frame insertion polymorphism in the murine Ltbp4 gene associates with partial protection against muscular dystrophy. In humans, nonsynonymous single nucleotide polymorphisms in LTBP4 associate with prolonged ambulation in Duchenne muscular dystrophy. To better understand LTBP4 and its role in modifying muscular dystrophy, we created transgenic mice overexpressing the protective murine allele of LTBP4 specifically in mature myofibers using the human skeletal actin promoter. Overexpression of LTBP4 protein was associated with increased muscle mass and proportionally increased strength compared to age-matched controls. In order to assess the effects of LTBP4 in muscular dystrophy, LTBP4 overexpressing mice were bred to mdx mice, a model of Duchenne muscular dystrophy. In this model, increased LTBP4 led to greater muscle mass with proportionally increased strength, and decreased fibrosis. The increase in muscle mass and reduction in fibrosis were similar to what occurs when myostatin, a related TGFβ family member and negative regulator of muscle mass, was deleted in mdx mice. Supporting this, we found that myostatin forms a complex with LTBP4 and that overexpression of LTBP4 led to a decrease in myostatin levels. LTBP4 also interacted with TGFβ and GDF11, a protein highly related to myostatin. These data identify LTBP4 as a multi-TGFβ family ligand binding protein with the capacity to modify muscle disease through overexpression. PMID:27148972

  8. Warm-up and stretching in the prevention of muscular injury.

    PubMed

    Woods, Krista; Bishop, Phillip; Jones, Eric

    2007-01-01

    Muscular injury is one of the major problems facing today's athletes, both recreational and professional. Injuries to skeletal muscle represent >30% of the injuries seen in sports medicine clinics. As a result, it is imperative to utilise the most effective means to aid in deterring these injuries. However, there are conflicting opinions regarding methods of reducing muscular injury through warm-up and stretching techniques.Therefore, the purpose of this article is to examine the potential of a warm-up and/or stretching routine in deterring muscular injury during physical activity. The article examines a variety of studies regarding warm-up, stretching and muscular injury. The article also provides a definition of warm-up and stretching to provide clarity on this topic. Many of the differences within previous research were due to conflicting definitions. We also address this issue by examining research on muscular injury and physical adaptations to muscular injury and training. This article provides contradictory evidence to conclusions that have been drawn in previous review articles, which determined that warm-up and/or stretching protocols did not deter injury. The research included here conveys that certain techniques and protocols have shown a positive outcome on deterring injuries. As a result, a warm-up and stretching protocol should be implemented prior to physical activity. The routine should allow the stretching protocol to occur within the 15 minutes immediately prior to the activity in order to receive the most benefit. In addition, current information regarding improvements in flexibility is reviewed.

  9. Distinctive serum miRNA profile in mouse models of striated muscular pathologies.

    PubMed

    Vignier, Nicolas; Amor, Fatima; Fogel, Paul; Duvallet, Angélique; Poupiot, Jérôme; Charrier, Sabine; Arock, Michel; Montus, Marie; Nelson, Isabelle; Richard, Isabelle; Carrier, Lucie; Servais, Laurent; Voit, Thomas; Bonne, Gisèle; Israeli, David

    2013-01-01

    Biomarkers are critically important for disease diagnosis and monitoring. In particular, close monitoring of disease evolution is eminently required for the evaluation of therapeutic treatments. Classical monitoring methods in muscular dystrophies are largely based on histological and molecular analyses of muscle biopsies. Such biopsies are invasive and therefore difficult to obtain. The serum protein creatine kinase is a useful biomarker, which is however not specific for a given pathology and correlates poorly with the severity or course of the muscular pathology. The aim of the present study was the systematic evaluation of serum microRNAs (miRNAs) as biomarkers in striated muscle pathologies. Mouse models for five striated muscle pathologies were investigated: Duchenne muscular dystrophy (DMD), limb-girdle muscular dystrophy type 2D (LGMD2D), limb-girdle muscular dystrophy type 2C (LGMD2C), Emery-Dreifuss muscular dystrophy (EDMD) and hypertrophic cardiomyopathy (HCM). Two-step RT-qPCR methodology was elaborated, using two different RT-qPCR miRNA quantification technologies. We identified miRNA modulation in the serum of all the five mouse models. The most highly dysregulated serum miRNAs were found to be commonly upregulated in DMD, LGMD2D and LGMD2C mouse models, which all exhibit massive destruction of striated muscle tissues. Some of these miRNAs were down rather than upregulated in the EDMD mice, a model without massive myofiber destruction. The dysregulated miRNAs identified in the HCM model were different, with the exception of one dysregulated miRNA common to all pathologies. Importantly, a specific and distinctive circulating miRNA profile was identified for each studied pathological mouse model. The differential expression of a few dysregulated miRNAs in the DMD mice was further evaluated in DMD patients, providing new candidates of circulating miRNA biomarkers for DMD.

  10. In Vivo Dynamic Deformation of Articular Cartilage in Intact Joints Loaded by Controlled Muscular Contractions.

    PubMed

    Abusara, Ziad; Von Kossel, Markus; Herzog, Walter

    2016-01-01

    When synovial joints are loaded, the articular cartilage and the cells residing in it deform. Cartilage deformation has been related to structural tissue damage, and cell deformation has been associated with cell signalling and corresponding anabolic and catabolic responses. Despite the acknowledged importance of cartilage and cell deformation, there are no dynamic data on these measures from joints of live animals using muscular load application. Research in this area has typically been done using confined and unconfined loading configurations and indentation testing. These loading conditions can be well controlled and allow for accurate measurements of cartilage and cell deformations, but they have little to do with the contact mechanics occurring in a joint where non-congruent cartilage surfaces with different material and functional properties are pressed against each other by muscular forces. The aim of this study was to measure in vivo, real time articular cartilage deformations for precisely controlled static and dynamic muscular loading conditions in the knees of mice. Fifty and 80% of the maximal knee extensor muscular force (equivalent to approximately 0.4N and 0.6N) produced average peak articular cartilage strains of 10.5±1.0% and 18.3±1.3% (Mean ± SD), respectively, during 8s contractions. A sequence of 15 repeat, isometric muscular contractions (0.5s on, 3.5s off) of 50% and 80% of maximal muscular force produced cartilage strains of 3.0±1.1% and 9.6±1.5% (Mean ± SD) on the femoral condyles of the mouse knee. Cartilage thickness recovery following mechanical compression was highly viscoelastic and took almost 50s following force removal in the static tests.

  11. Impact of three genetic musculoskeletal diseases: a comparative synthesis of achondroplasia, Duchenne muscular dystrophy and osteogenesis imperfecta.

    PubMed

    Dogba, Maman Joyce; Rauch, Frank; Douglas, Erin; Bedos, Christophe

    2014-10-25

    Achondroplasia, Duchenne muscular dystrophy, and osteogenesis imperfecta are among the most frequent rare genetic disorders affecting the musculoskeletal system in children. Rare genetic disorders are severely disabling and can have substantial impacts on families, children, and on healthcare systems. This literature review aims to classify, summarize and compare these non-medical impacts of achondroplasia, Duchenne muscular dystrophy and osteogenesis imperfecta.

  12. Adaptations in muscular activation of the knee extensor muscles with strength training in young and older adults.

    PubMed

    Knight, C A; Kamen, G

    2001-12-01

    The purpose of this study was to compare the extent of muscular activation during maximal voluntary knee extension contractions in old and young individuals and to examine the effects of resistance training on muscular activation in each group. The interpolated twitch technique was used to estimate muscular activation during two pre-training baseline tests, and after two and six weeks of resistance training. Throughout the study, the older group was 30% less strong than the young group (p=0.02). The training protocol was effective in both groups with overall isometric strength gains of 30 and 36% in the older (p=0.01) and young (p<0.01) groups, respectively. 10-RM training loads increased by 66% in the old group (p<0.01) and by 77% in the young group (p<0.01) throughout training. At the first baseline test, a 2% difference in muscular activation between groups (p=0.3) did not explain the large disparity in strength. Muscular activation increased by 2% in both groups throughout training (p<0.01). Despite considerably less muscular strength in the older group, muscular activation was greater than 95% of maximum and appears to be equal in both young and older individuals. Both groups demonstrated similar but small increases in muscular activation throughout training.

  13. Using hegemonic masculinity to explain gay male attraction to muscular and athletic men.

    PubMed

    Lanzieri, Nicholas; Hildebrandt, Tom

    2011-01-01

    This article reviews relevant research on male homosexual attraction. Utilizing masculinity as its theoretical frame, the authors use childhood experiences with both fathers and peers, the gay community's inculcation of heteronormative ideologies, and the gay media's adherence to masculine prototypes, to provide causal explanations for the appeal of muscular, lean, and athletic physiques. While the authors acknowledge that not all individuals within the gay community look toward muscularity and athleticism as the primary components of attractiveness, it nonetheless remains important to examine the theoretical perspectives that may explain the appeal of this specific aesthetic.

  14. Becker muscular dystrophy with widespread muscle hypertrophy and a non-sense mutation of exon 2.

    PubMed

    Witting, N; Duno, M; Vissing, J

    2013-01-01

    Becker muscular dystrophy features progressive proximal weakness, wasting and often focal hypertrophy. We present a patient with pain and cramps from adolescence. Widespread muscle hypertrophy, preserved muscle strength and a 10-20-fold raised CPK were noted. Muscle biopsy was dystrophic, and Western blot showed a 95% reduction of dystrophin levels. Genetic analyses revealed a non-sense mutation in exon 2 of the dystrophin gene. This mutation is predicted to result in a Duchenne phenotype, but resulted in a mild Becker muscular dystrophy with widespread muscle hypertrophy. We suggest that this unusual phenotype is caused by translation re-initiation downstream from the mutation site.

  15. Evidence for linkage disequilibrium in chromosome 13-linked Duchenne-like muscular dystrophy

    SciTech Connect

    Othmane, K.B.; Speer, M.C.; Stauffer, J.

    1995-09-01

    Duchenne-like muscular dystrophy (DLMD) is an autosomal recessive Limb Girdle muscular dystrophy (LGMD2C) characterized by late age of onset, proximal muscle weakness leading to disability, high creatine kinase values, normal intelligence and normal dystrophin in muscle biopsy. We have shown previously that three DLMD families from Tunisia are linked to chromosome 13q12. To further localize the LGMD2C gene, we have investigated seven additional families (119 individuals). Both genotyping and two-point linkage analysis were performed as described elsewhere. 7 refs., 1 fig., 1 tab.

  16. Cytokines and Chemokines as Regulators of Skeletal Muscle Inflammation: Presenting the Case of Duchenne Muscular Dystrophy

    PubMed Central

    De Bleecker, Jan L.

    2013-01-01

    Duchenne muscular dystrophy is a severe inherited muscle disease that affects 1 in 3500 boys worldwide. Infiltration of skeletal muscle by inflammatory cells is an important facet of disease pathophysiology and is strongly associated with disease severity in the individual patient. In the chronic inflammation that characterizes Duchenne muscle, cytokines and chemokines are considered essential activators and recruiters of inflammatory cells. In addition, they provide potential beneficiary effects on muscle fiber damage control and tissue regeneration. In this review, current knowledge of cytokine and chemokine expression in Duchenne muscular dystrophy and its relevant animal disease models is listed, and implications for future therapeutic avenues are discussed. PMID:24302815

  17. [ASSOCIATION BETWEEN MUSCULAR FITNESS AND PHYSICAL HEALTH STATUS AMONG CHILDREN AND ADOLESCENTS FROM BOGOTÁ, COLOMBIA].

    PubMed

    Rodríguez Valero, Francisco Javier; Gualteros, Julian Alberto; Torres, Jorge Andres; Umbarila Espinosa, Luz Marina; Ramírez-Velez, Robinson

    2015-10-01

    Objetivo: la evidencia epidemiológica y experimental sugieren que la disminución de la fuerza muscular en las etapas tempranas de la vida se asocia de manera independiente con la presencia de factores de riesgo asociados a enfermedad cardiometabólica en la edad adulta. El objetivo de este estudio fue examinar la asociación entre el desempeño muscular y el bienestar físico de niños y adolescentes de Bogotá, Colombia. Métodos: estudio transversal, realizado en 921 niños y adolescentes de entre 9 y 17 años de Bogotá, Colombia. Se calculó el Índice General de Fuerza (IGF) como marcador del desempeño muscular con las pruebas de salto longitud sin impulso, salto vertical y dinamometría manual. El IGF se recodificó en cuartiles, siendo el cuartil (Q4) la posición con mejor valor del desempeño muscular. El índice de masa corporal (IMC), los pliegues cutáneos, la circunferencia de cintura y de cadera, la composición corporal por bioimpedancia (BIA), la tensión arterial y la autodeclaración de maduración sexual se midieron como indicadores del bienestar físico asociados a enfermedad cardiovascular futura. Resultados: la edad media de los evaluados fue 13,0 ± 2,6 años. Los participantes con mejor desempeño muscular (Q4) presentaron un bienestar físico más saludable en los indicadores IMC, tensión arterial, porcentaje de grasa y circunferencia de cintura, p (X2 lineal) = 0,01. Los individuos con menor desempeño muscular (Q1-3) presentaron 4,06 veces (IC 95% 2,60–6,34; p = 0,043) riesgo de exceso de grasa corporal y 1,57 veces (IC 95% 1,02–1,89; p = 0,020) riesgo de obesidad abdominal. Conclusión: el mejor desempeño muscular se asoció con mejores indicadores del bienestar físico. La evaluación de la fuerza muscular en edades tempranas permitirá implementar programas de prevención de riesgo cardiovascular y metabólico futuros.

  18. A longitudinal investigation of the Drive for Muscularity Scale: predicting use of performance enhancing substances and weightlifting among males.

    PubMed

    Litt, Dana; Dodge, Tonya

    2008-12-01

    The present study was designed to examine the predictive validity of the Drive for Muscularity Scale (DMS; McCreary & Sasse, 2000). The drive for muscularity scale (DMS) is comprised of two subscales: a muscularity-oriented body image (MBI) subscale and a muscularity behavior (MB) subscale. The present study tested whether these subscales predicted two behavioral outcomes in the context of a longitudinal design: use of performance enhancing substances (PES) and weightlifting behavior. One hundred and sixty-one male undergraduates completed a questionnaire that assessed the drive for muscularity, PES use and weightlifting behavior at Time 1 and again 6 weeks later. Results indicated that the MB subscale at Time 1 significantly predicted both changes in PES use and weightlifting behavior controlling for past substance use and past weightlifting behavior. The MBI subscale failed to predict either changes in PES use or weightlifting behavior. Implications and directions for future research are discussed.

  19. The effects of exposure to muscular male models among men: exploring the moderating role of gym use and exercise motivation.

    PubMed

    Halliwell, Emma; Dittmar, Helga; Orsborn, Amber

    2007-09-01

    This study examines the effects of exposure to the muscular male body ideal on body-focused negative affect among male gym users and non-exercisers. As hypothesized, the impact of media exposure depended on men's exercise status. Non-exercisers (n = 58) reported greater body-focused negative affect after exposure to images of muscular male models than after neutral images (no model controls), whereas gym users (n = 58) showed a tendency for less body-focused negative affect after the model images than after the control images. Furthermore, the extent to which gym users were motivated to increase strength and muscularity moderated these exposure effects; men who reported stronger strength and muscularity exercise motivation reported a greater degree of self-enhancement after exposure to the muscular ideal. The findings are interpreted with respect to likely differences in motives for social comparisons.

  20. Cardiac manifestations of congenital LMNA-related muscular dystrophy in children: three case reports and recommendations for care.

    PubMed

    Heller, Felice; Dabaj, Ivana; Mah, Jean K; Bergounioux, Jean; Essid, Aben; Bönnemann, Carsten G; Rutkowski, Anne; Bonne, Gisèle; Quijano-Roy, Susana; Wahbi, Karim

    2016-12-12

    Skeletal and cardiac muscle laminopathies, caused by mutations in the lamin A/C gene, have a clinical spectrum from congenital LMNA-related muscular dystrophy to later-onset Emery-Dreifuss muscular dystrophy, limb girdle muscular dystrophy, and dilated cardiomyopathy. Although cardiac involvement is observed at all ages, it has only been well described in adults. We present the evolution of cardiac disease in three children with congenital muscular dystrophy presentation of LMNA-related muscular dystrophy. In this series, atrial arrhythmia was the presenting cardiac finding in all three patients. Heart failure developed up to 5 years later. Symptoms of right heart failure, including diarrhoea and peripheral oedema, preceded a rapid decline in left ventricular ejection fraction. Recommendations for cardiac surveillance and management in these patients are made.

  1. [Evolution of functional capacity, assessed with the Egen Klassifikation scale, in the Spanish population with spinal muscular atrophy or Duchenne muscular dystrophy. A three year longitudinal study].

    PubMed

    Fagoaga, J; Girabent-Farres, M; Bagur-Calafat, C; Steffensen, B F

    2015-10-16

    Introduccion. La atrofia muscular espinal (AME) y la distrofia muscular de Duchenne (DMD) son dos enfermedades neuromusculares que evolucionan con perdida progresiva de la fuerza muscular y, en consecuencia, perdida de la capacidad funcional. La valoracion con escalas de medicion permite conocer mejor y cuantificar esta involucion, asi como tomar decisiones terapeuticas para anticiparse a los problemas y mejorar la calidad de vida de las personas afectas de estas patologias. Objetivo. Estudiar los cambios de la capacidad funcional de un grupo de pacientes con AME y DMD en un periodo de tres años. Pacientes y metodos. Diecinueve personas de la poblacion española afectas de AME o DMD, a las que se valoro con la escala Egen Klassifikation en dos ocasiones, en un periodo de tres años. Resultados. Los resultados obtenidos reflejan una disminucion de la capacidad funcional de estas personas durante este periodo de tiempo, con una diferencia significativa en la suma total de la escala (p = 0,003). Todos los items de la escala tuvieron valoraciones inferiores despues de tres años, y se llego a la significacion estadistica en la valoracion de la capacidad de mover las manos y de toser. Conclusion. La capacidad funcional de los pacientes con AME y DMD disminuye de forma significativa en tres años.

  2. [Changes of ultrastructure of the capillary endotheliocytes of ischemized and nonaffected muscular tissue after transplantation of human hemopoietic stem cells of fetal liver in experiment in vivo].

    PubMed

    Saliutin, R V; Zadorozhna, T D; Medvets'kyĭ, E B; Driuk, M F; Petrenko, A Iu

    2010-04-01

    In experiment was investigated ultrastructure of the capillaries endothelial cells and histological peculiarities of muscular tissue on various stages after transplantation of hemopoietic stem cells of fetal liver (HSCFL). There was proved, that in ischemic environment HSCFL stimulate processes of angiogenesis, and in the case of transplantation into intact muscular tissue they are differentiating into the tissue macrophages, not interfering with muscular tissue structure.

  3. Identification of system misregistrations during AO-corrected observations

    NASA Astrophysics Data System (ADS)

    Béchet, C.; Thiébaut, É.; .; Tallon, M.; Kolb, J.; Madec, P.-Y.

    2011-09-01

    The E-ELT will be equipped with a deformable mirror inside the telescope. The performance of reconstruction and control depends on the calibration of the interaction matrix- or a model of the interaction matrix- , which characterizes the system and the relationship between the commands sent to the deformable mirrors (DM) and the wavefront sensors (WFS) slopes. Such a calibration will be more complex than for the current systems at the VLT since it will have to be at least partly measured on sky and for a much larger number of degrees of freedom (more than 5000). In addition, gravity or temperature variations for instance are likely to introduce slow evolution of the matching between the M4 Deformable mirror and the WFS geometry. This can occur during observations and therefore degrade the adaptive optics (AO) correction. To relax the need of frequent painful calibrations and to prevent a loss of performance due to misregistrations, we investigate how to track the evolution of the interaction matrix errors in closed-loop without introducing any degradation in the observations. This is done thanks to identification methods and optimization theory. First, we formally describe the problem and the difficulties of such an identification in closed-loop configuration. Then, we present 2 solutions, based on the optimization of the error of estimates of the WFS slopes, at the output of the closed-loop AO. The performance of the methods and their limitations are discussed formally and thanks to numerical simulations of a high order AO system. We finally explore to which extent these methods currently studied for the Adaptive Optics Facility (AOF) at the VLT can be applied to the E-ELT.

  4. Green FLASH: energy efficient real-time control for AO

    NASA Astrophysics Data System (ADS)

    Gratadour, D.; Dipper, N.; Biasi, R.; Deneux, H.; Bernard, J.; Brule, J.; Dembet, R.; Doucet, N.; Ferreira, F.; Gendron, E.; Laine, M.; Perret, D.; Rousset, G.; Sevin, A.; Bitenc, U.; Geng, D.; Younger, E.; Andrighettoni, M.; Angerer, G.; Patauner, C.; Pescoller, D.; Porta, F.; Dufourcq, G.; Flaischer, A.; Leclere, J.-B.; Nai, A.; Palazzari, P.; Pretet, D.; Rouaud, C.

    2016-07-01

    The main goal of Green Flash is to design and build a prototype for a Real-Time Controller (RTC) targeting the European Extremely Large Telescope (E-ELT) Adaptive Optics (AO) instrumentation. The E-ELT is a 39m diameter telescope to see first light in the early 2020s. To build this critical component of the telescope operations, the astronomical community is facing technical challenges, emerging from the combination of high data transfer bandwidth, low latency and high throughput requirements, similar to the identified critical barriers on the road to Exascale. With Green Flash, we will propose technical solutions, assess these enabling technologies through prototyping and assemble a full scale demonstrator to be validated with a simulator and tested on sky. With this R&D program we aim at feeding the E-ELT AO systems preliminary design studies, led by the selected first-light instruments consortia, with technological validations supporting the designs of their RTC modules. Our strategy is based on a strong interaction between academic and industrial partners. Components specifications and system requirements are derived from the AO application. Industrial partners lead the development of enabling technologies aiming at innovative tailored solutions with potential wide application range. The academic partners provide the missing links in the ecosystem, targeting their application with mainstream solutions. This increases both the value and market opportunities of the developed products. A prototype harboring all the features is used to assess the performance. It also provides the proof of concept for a resilient modular solution to equip a large scale European scientific facility, while containing the development cost by providing opportunities for return on investment.

  5. 76 FR 4726 - Avaya Global Services, AOS Service Delivery, Worldwide Services Group, Including Workers Whose...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-26

    ... insurance (UI) tax account under the name Nortel Networks, Inc. and Avaya Global Services, AOS Service... unemployment (UI) wages are reported through Nortel Networks, Inc. and Avaya Global Services, AOS Service... Nortel Networks, Inc., Billerica, Massachusetts (TA-W-74,411B); Avaya Global Services, AOS...

  6. Measuring Geosynchronous Satellites from Stellar Appulses with AO

    DTIC Science & Technology

    2014-09-01

    geosynchronous satellites using adaptive optics on our 3.5 m telescope with a Laser Guide Star (LGS) and without a laser (Natural Guide Star, NGS), we found two...adaptive optics on our 3.5 m telescope with a Laser Guide Star (LGS) and without a laser (Natural Guide Star, NGS), we found two satellites in the... telescope using NGS AO, we targeted a geo, satellite 28868 ANIK F1-R, for study. We imaged it intermittently for 23 minutes, noticing 7 passing stars in

  7. Intramedullary locking femoral nails. Experience with the AO nail.

    PubMed Central

    Fogarty, A. B.; Yeates, H. A.

    1991-01-01

    The AO interlocking nail was introduced to the Ulster Hospital, Dundonald in 1988 and since then has been used in over 50 patients with femoral shaft fractures. We have reviewed 45 patients with 46 femoral shaft fractures treated between June 1988 and April 1990. These included four compound fractures and 13 comminuted fractures. The results compare favourably with other series. The union rate was 98% and there were no instances of deep infection. The alternative treatment methods available are discussed along with a review of the relevant literature. Images Fig 3 Fig 5 PMID:1785145

  8. LDEF (Postflight), AO201 : Interplanetary Dust Experiment, Tray C03

    NASA Technical Reports Server (NTRS)

    1990-01-01

    LDEF (Postflight), AO201 : Interplanetary Dust Experiment, Tray C03 The IDE mounting plate and the detector frames are coated with a brown stain similiar to that seen on the other experiments in this and other trays located nearby. The stain seems to be slightly darker along the lower edge of the solar sensor mounting plate. The colors and designs seen on the detectors are reflections of the surrounding area. The thin brown film on the detectors metallic surface has resulted in a duller reflection of a technician, in the upper left, and other items.

  9. Which one Enhances Muscular Performance in ACL Reconstructed Subjects

    PubMed Central

    Harput, Gulcan; Ulusoy, Burak; Atay, Ahmet Ozgur; Baltacı, Gul

    2014-01-01

    Objectives: The aim of this study was to investigate the effects of functional knee brace and kinesiotaping on muscular performance in anterior cruciate ligament reconstructed subjects who reached return to sport phase of the rehabilitation. Methods: Twenty (17 males, 3 females, Age: 24.7±7.1 years, Body weight: 74.4±12.0 kg, Height: 177.9±6.5 cm, BMI: 23.9±3.6 kg/m2) subjects who underwent anterior cruciate ligament reconstruction by using hamstring tendon auto graft were included in this study. When the subjects reached the return to sports phase of rehabilitation which was 6th months after surgery, knee muscle strength, jump performance and balance tests were performed 3 times: bare, with knee brace and with kinesio taping. The order of the tests were randomized to eliminate the effects of fatigue and motor learning. Quadriceps and hamstring muscle strength was measured on an isokinetic dynamometer at 180 °/s and 60°/s angular velocities. Vertical Jump (VJ) and One Leg Hop Tests (OLHT) were used to assess jump performance. Star Excursion Balance Test (SEBT) with anterior, posteromedial and posterolateral reach distance was used to assess the dynamic balance. When all tests were performed, the subjects were asked under which test condition they felt more confident. Repeated measures of ANOVA was used to analyze the difference among three test conditions (bare, kinesiotaping, knee brace). Bonferroni post hoc test was used for pairwise comparison. Results: SEBT posteromedial (PM)and posterolateral (PL) reach distances were found significantly different among three test conditions(PM: F(2,38)=3.42,p=0.04), PL: F(2,38)=4.37,p=0.02). Kinesiotaping increased posteromedial reach distance (p=0.03). On the other hand, brace decreased posterolateral reach distance (p=0.04). VJ and OLHT performance were also found significantly different between three test conditions (VJ: F (2,38)=3.44,p=0.04, OLHT: (F(2,38)=4.04,p=0.02). Kinesio taping increased one leg hop distance

  10. Media exposure, mediated social comparison to idealized images of muscularity, and anabolic steroid use.

    PubMed

    Melki, Jad P; Hitti, Eveline A; Oghia, Michael J; Mufarrij, Afif A

    2015-01-01

    This study examined the association between anabolic-androgenic steroid (AAS) use and dominant sociocultural factors, specifically media exposure to idealized images of male muscularity, and mediated social comparison trends among a sample of young Arab adults. The study found evidence that participants more exposed to content that promotes muscularity and those who idealize images of muscularity and perceive them as motivators for achieving muscularity are more likely to be AAS users. It also found that a significant percentage of participants used at least one kind of dietary supplement and that the level of AAS use among health club participants indicates it is a significant public health problem in Lebanon. The study suggests that dealing with this problem requires a unique approach, beyond the typical awareness of risks strategy, since some users were well aware of the risks yet continue to use AAS, and their motivations pertain more to body image and sexuality. A stronger approach that utilizes critical media literacy teaching that ingrains these issues into school and university curricula will have a more lasting impact.

  11. The Effects of Muscular Fatigue on the Kinetics of Sprint Running.

    ERIC Educational Resources Information Center

    Sprague, Paul; Mann, Ralph V.

    1983-01-01

    To compare the kinematic and kinetic effects of fatigue on the biomechanics of sprint running, male subjects were filmed performing a short maximal exertion sprint and a long fatiguing sprint. Observable differences in the productive muscular activity of the better and the poorer sprinters occurred during the ground-phase of their strides.…

  12. Cardiac Involvement Classification and Therapeutic Management in Patients with Duchenne Muscular Dystrophy.

    PubMed

    Fayssoil, Abdallah; Abasse, Soumeth; Silverston, Katy

    2017-01-01

    Duchenne muscular dystrophy (DMD) is an inherited myogenic disorder due to mutations in the dystrophin gene on chromosome Xp21.1. The clinical picture included peripheral muscle weakness, cardiomyopathy and chronic respiratory insufficiency. In this paper, the authors review cardiac involvement in patients with DMD, propose a cardiac impairment classification and discuss therapeutic management options.

  13. Na+ Dysregulation Coupled with Ca2+ Entry through NCX1 Promotes Muscular Dystrophy in Mice

    PubMed Central

    Burr, Adam R.; Millay, Douglas P.; Goonasekera, Sanjeewa A.; Park, Ki Ho; Sargent, Michelle A.; Collins, James; Altamirano, Francisco; Philipson, Kenneth D.; Allen, Paul D.; Ma, Jianjie; López, José Rafael

    2014-01-01

    Unregulated Ca2+ entry is thought to underlie muscular dystrophy. Here, we generated skeletal-muscle-specific transgenic (TG) mice expressing the Na+-Ca2+ exchanger 1 (NCX1) to model its identified augmentation during muscular dystrophy. The NCX1 transgene induced dystrophy-like disease in all hind-limb musculature, as well as exacerbated the muscle disease phenotypes in δ-sarcoglycan (Sgcd−/−), Dysf−/−, and mdx mouse models of muscular dystrophy. Antithetically, muscle-specific deletion of the Slc8a1 (NCX1) gene diminished hind-limb pathology in Sgcd−/− mice. Measured increases in baseline Na+ and Ca2+ in dystrophic muscle fibers of the hind-limb musculature predicts a net Ca2+ influx state due to reverse-mode operation of NCX1, which mediates disease. However, the opposite effect is observed in the diaphragm, where NCX1 overexpression mildly protects from dystrophic disease through a predicted enhancement in forward-mode NCX1 operation that reduces Ca2+ levels. Indeed, Atp1a2+/− (encoding Na+-K+ ATPase α2) mice, which have reduced Na+ clearance rates that would favor NCX1 reverse-mode operation, showed exacerbated disease in the hind limbs of NCX1 TG mice, similar to treatment with the Na+-K+ ATPase inhibitor digoxin. Treatment of Sgcd−/− mice with ranolazine, a broadly acting Na+ channel inhibitor that should increase NCX1 forward-mode operation, reduced muscular pathology. PMID:24662047

  14. SIRT1: A Novel Target for the Treatment of Muscular Dystrophies

    PubMed Central

    Kuno, Atsushi; Horio, Yoshiyuki

    2016-01-01

    Muscular dystrophies are inherited myogenic disorders accompanied by progressive skeletal muscle weakness and degeneration. Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy and is caused by mutations in the gene that encodes the cytoskeletal protein dystrophin. The treatment for DMD is limited to glucocorticoids, which are associated with multiple side effects. Thus, the identification of novel therapeutic targets is urgently needed. SIRT1 is an NAD+-dependent histone/protein deacetylase that plays roles in diverse cellular processes, including stress resistance and cell survival. Studies have shown that SIRT1 activation provides beneficial effects in the dystrophin-deficient mdx mouse, a model of DMD. SIRT1 activation leads to the attenuation of oxidative stress and inflammation, a shift from the fast to slow myofiber phenotype, and the suppression of tissue fibrosis. Although further research is needed to clarify the molecular mechanisms underlying the protective role of SIRT1 in mdx mice, we propose SIRT1 as a novel therapeutic target for patients with muscular dystrophies. PMID:27073590

  15. Mild and severe muscular dystrophy caused by a single gamma-sarcoglycan mutation.

    PubMed Central

    McNally, E. M.; Passos-Bueno, M. R.; Bönnemann, C. G.; Vainzof, M.; de Sá Moreira, E.; Lidov, H. G.; Othmane, K. B.; Denton, P. H.; Vance, J. M.; Zatz, M.; Kunkel, L. M.

    1996-01-01

    Autosomal recessive muscular dystrophy is genetically heterogeneous. One form of this disorder, limb-girdle muscular dystrophy type 2C (LGMD 2C), is prevalent in northern Africa and has been shown to be associated with a single mutation in the gene encoding the dystrophin-associated protein gamma-sarcoglycan. The previous mutation analysis of gamma-sarcoglycan required the availability of muscle biopsies. To establish a mutation assay for genomic DNA, the intron-exon structure of the gamma-sarcoglycan gene was determined, and primers were designed to amplify each of the exons encoding gamma-sarcoglycan. We studied a group of Brazilian muscular dystrophy patients for mutations in the gamma-sarcoglycan gene. These patients were selected on the basis of autosomal inheritance and/or the presence of normal dystrophin and/or deficiency of alpha-sarcoglycan immunostaining. Four of 19 patients surveyed had a single, homozygous mutation in the gamma-sarcoglycan gene. The mutation identified in these patients, all of African-Brazilian descent, is identical to that seen in the North African population, suggesting that even patients of remote African descent may carry this mutation. The phenotype in these patients varied considerably. Of four families with an identical mutation, three have a severe Duchenne-like muscular dystrophy. However, one family has much milder symptoms, suggesting that other loci may be present that modify the severity of the clinical course resulting from gamma-sarcoglycan gene mutations. Images Figure 2 Figure 5 PMID:8900232

  16. Changes of muscular load with aging in the motion of pulling up disposable diapers.

    PubMed

    Yoto, Tsuyoshi Yi; Sakuragawa, Satoshi; Suzuki, Taka-aki; Tamura, Hisae; Yamaki, Rumi; Fujioka, Yoshihisa; Katsuura, Tetsuo

    2010-01-01

    To elucidate how aging affects the muscular load required for pulling up pants-style disposable diapers, and why some elderly people cannot pull up the rear of their disposable diapers well, we evaluated the electromyogram (EMG) of 8 young subjects (21.5+/-1.5 years) and 7 elderly subjects (71.6+/-6.1 years). EMG was measured for four muscles--biceps brachii, deltoid, brachioradialis, and flexor carpi ulnaris. We evaluated the muscular load during a series of motions for pulling a disposable diaper up at the front and the rear of the body using an EMG-Video Synchronous Split Method. The analysis revealed that the front and the rear integral EMG of elderly subjects were both significantly larger than those of young subjects for all four muscles. For the deltoid and flexor carpi ulnaris muscles, the maximum amplitude of EMG when pulling up the rear of the disposable diapers was significantly larger in the elderly subjects than the young ones. These results suggest that the muscular load involved in pulling up the rear of disposable diapers may increase due to changes in body habitus caused by aging. Since muscular strength decreases with age, it seems likely that the elderly individuals will eventually be unable to pull up the rear of their diapers.

  17. Second international workshop for glycosylation defects in muscular dystrophies, 11-12 November, 2010, Charlotte, USA.

    PubMed

    Chan, Yiumo M; Brown, Susan C; Lu, Qi

    2011-11-01

    The second International Workshop for Glycosylation Defects in Muscular Dystrophies took place on November 11 and 12, 2010 in Charlotte, North Carolina, USA. The meeting was hosted by the Carolinas Medical Center with financial support from the Carolinas Muscular Dystrophy Research Endowment at the Carolinas HealthCare Foundation, the Muscular Dystrophy Association and funds raised by the "Jeans, Genes & Geniuses" event organized by Jane and Luther Lockwood. Since conducting the first workshop in May 2008, significant progress has been made in a subset of muscular dystrophies associated with defects in alpha-dystroglycan (α-DG) glycosylation. New findings on α-DG glycosylation and creation of novel animal models have expanded our understanding of the disease mechanism. The 2010 workshop focused on the following topics; (i) functional glycosylation of α-DG; (ii) animal models; and (iii) novel experimental therapies. The workshop brought together a total of 22 internationally renowned scientists and clinicians from US, UK, Denmark and Japan with active research and expertise in these areas. Overall, the workshop provided a unique opportunity to discuss the significance of recent progress, facilitate international collaboration, and identify new approaches to treat the disease.

  18. The time to and determinants of first fractures in boys with Duchenne muscular dystrophy.

    PubMed

    Ma, J; McMillan, H J; Karagüzel, G; Goodin, C; Wasson, J; Matzinger, M A; DesClouds, P; Cram, D; Page, M; Konji, V N; Lentle, B; Ward, L M

    2017-02-01

    Boys with vertebral fractures (VF) identified through routine spine radiographs had milder, less symptomatic, and fewer VF compared to those diagnosed with VF following consultation for back pain. Spontaneous (i.e., medication-unassisted) reshaping of fractured vertebral bodies was absent. Long bone fractures were present even before Duchenne muscular dystrophy (DMD) diagnosis in some boys.

  19. A Biopsychosocial Model of Disordered Eating and the Pursuit of Muscularity in Adolescent Boys

    ERIC Educational Resources Information Center

    Ricciardelli, Lina A.; McCabe, Marita P.

    2004-01-01

    This review provides an evaluation of the correlates and/or risk factors associated with disordered eating and the pursuit of muscularity among adolescent boys. One of the main conclusions is that similar factors and processes are associated with both behavioral problems. Several factors found to be consistently associated with disordered eating…

  20. Effects of multi-joint muscular fatigue on biomechanics of slips.

    PubMed

    Lew, Fui Ling; Qu, Xingda

    2014-01-03

    The objective of the present study was to investigate the effects of multi-joint muscular fatigue on biomechanics of slips. Both lower-limb fatigue and upper-limb fatigue were examined, and the fatiguing exercises involved multi-joint movements to replicate muscular fatigue in realistic scenarios. Sixty healthy young adults participated in the study, and were evenly categorized into three groups: no fatigue, lower-limb fatigue, and upper-limb fatigue. These participants were instructed to walk on a linear walkway, and slips were induced unexpectedly during walking. The results showed that multi-joint muscular fatigue affects biomechanics of slips in all three phases of slips (i.e. initiation, detection, and recovery). In particular, adaptive safer postural control strategies were adopted with the application of both lower-limb fatigue and upper-limb fatigue to maintain the likelihood of slip initiation as in the no fatigue condition. In the phases of detection and recovery, lower-limb fatigue was found to compromise biomechanics of slips while upper-limb fatigue did not show any effects. Based on these findings, minimizing exposures to lower-limb fatigue should be given higher priority compared to upper-limb fatigue when developing interventions to prevent slip-induced falls. In addition, these findings also suggest that interventions aimed at enhancing proprioceptive acuity and increasing muscular strength in the lower limb could also be effective in slip-induced fall prevention.