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This article discusses the development of precision diagnostics and treatment for Duchenne/Becker muscular dystrophy (DMD/BMD). It emphasizes the heterogeneity of these disorders and their impact on cardiac function and quality of life. The article suggests that a multi-faceted approach, including accurate genetic testing, personalized medicine, and clinical trials, is necessary to improve outcomes for individuals with DMD/BMD. Various researchers contribute to the article, discussing topics such as the impact on caregivers and potential treatment options. The article highlights the importance of advancing research and treatment options for DMD/BMD to enhance patient outcomes and quality of life. Another article titled "Psychological treatments, social and welfare support, and financial costs" explores the factors involved in providing support for individuals with psychological issues. It emphasizes the importance of psychological treatments and the need for social and welfare support. The article also touches on the financial costs associated with these forms of support. [Extracted from the article]

Dystrophin-deficient muscular dystrophy (Duchenne dystrophy) is characterized by impaired ion homeostasis, in which mitochondria play an important role. In the present work, using a model of dystrophin-deficient mdx mice, we revealed decrease in the efficiency of potassium ion transport and total content of this ion in the heart mitochondria. We evaluated the effect of chronic administration of the benzimidazole derivative NS1619, which is an activator of the large-conductance Ca2+-dependent K+ channel (mitoBKCa), on the structure and function of organelles and the state of the heart muscle. It was shown that NS1619 improves K+ transport and increases content of the ion in the heart mitochondria of mdx mice, but this is not associated with the changes in the level of mitoBKCa protein and expression of the gene encoding this protein. The effect of NS1619 was accompanied by the decrease in the intensity of oxidative stress, assessed by the level of lipid peroxidation products (MDA products), and normalization of the mitochondrial ultrastructure in the heart of mdx mice. In addition, we found positive changes in the tissue manifested by the decrease in the level of fibrosis in the heart of dystrophin-deficient animals treated with NS1619. It was noted that NS1619 had no significant effect on the structure and function of heart mitochondria in the wild-type animals. The paper discusses mechanisms of influence of NS1619 on the function of mouse heart mitochondria in Duchenne muscular dystrophy and prospects for applying this approach to correct pathology. [ABSTRACT FROM AUTHOR]

Background: Advances in healthcare systems with new therapeutic options improve the life expectancy of patients with neuromuscular diseases. With this, a shift in the phenotype of the diseases from the neuromuscular system towards other organs is more frequently observed, requiring closer interdisciplinary cooperation in caring for these young adults. Therefore, the transition to the adult caring system is nowadays a multilayered transfer with the need for complex care of these patients. Objective: How can the transitional process be efficiently structured to combine the therapeutic effort of each specialist discipline involved and improve the healthcare process and quality of life in young adults with neuromuscular diseases? Material and method: The Departments of Neuropediatrics and Neurology of the University Medicine Essen established the Essen transition model for a structured transitional process. A concept of care was developed for the late onset Pompe's disease, Duchenne muscular dystrophy and juvenile myasthenia gravis representatively for neuromuscular diseases. It consists of four components: 1) In a standardized operational procedure (SOP), general processes, clinical diagnostic steps and guidance of treatment between the two departments are harmonized and specified. 2) The young adults and their relatives are seen in a joint consultation of both disciplines allowing a comprehensive handover for healthcare professionals. 3) In a quarterly meeting, transition conference representatives from the different specialized disciplines from pediatric and adult medicine get together for a case-related interdisciplinary exchange. 4) An interdepartmental transitional database was created to integrate all diagnostic results and parameters as a common information platform and data basis. Conclusion: The Essen transition model aims to close a gap in the transition of patients with neuromuscular diseases and improve healthcare in these patients with their complex needs. [ABSTRACT FROM AUTHOR]

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Duchenne de Boulogne was one of the founders of clinical neurology. His name has been eponymically linked to the most common form of muscular dystrophy, originally described by him as pseudo-hypertrophic muscular paralysis or myo-sclerotic paralysis. Obtaining muscle biopsy specimens was essential to gain insight about the etiopathogenensis of the disease. Duchenne invented a novel instrument: l'emporte-pièce histologique, also known as "Duchenne's trocar," to perform muscle biopsies. Following Duchenne's design and instructions, a Parisian company, Charrière, constructed the first instrument probably in 1864. That instrument was essential for Duchenne's description of the histopathological abnormalities typical of pseudo-hypertrophic muscular paralysis. The innovative needle-biopsy technique enabled physicians to analyze the spectrum of pathological changes at varying stages of different neuromuscular diseases. Duchenne's trocar was a forerunner of several types of modern muscle-biopsy needles. His invention was instrumental in the development of the disciplines of muscle pathology and clinical myology. [ABSTRACT FROM AUTHOR]

Utrophin expression was investigated in two phenotypically discordant Duchenne muscular dystrophy half-brothers. The youngest was wheelchair-bound at age 9, while his mildly affected older brother was able to walk without difficulties at age 15. DNA analysis revealed an out-of-frame exon 2 duplication in the DMD gene, associated with muscle dystrophin protein deficiency. Utrophin localization and quantity was analyzed and compared in both sibs to verify whether this could explain the milder phenotype of the older brother. Immunofluorescence analysis showed a clear sarcolemmal labeling for utrophin in both of them, which was present in regenerating as well as in mature fibers. On western blot analysis, utrophin amount was increased 3.4 and 3.3 fold respectively, as compared to normal controls, while it was increased 1.7 to 4.0 fold in a group of DMD patients within the typical range of clinical progression. These data are in accordance with our previous observations suggesting no correlation between phenotype severity and utrophin up-regulation or sarcolemmal localization in dystrophinopathies. Finding the protective mechanisms in patients with milder course is of utmost interest to direct therapeutic targets. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD), a severe and lethal condition, is caused by the absence of muscle dystrophin. Therapeutic trials aiming at the amelioration of muscle function have been targeting the production of muscle dystrophin in affected Duchenne patients. However, how much dystrophin is required to rescue the DMD phenotype remains an open question. We have previously identified two exceptional golden retriever muscular dystrophy (GRMD) dogs with a milder course despite the total absence of muscle dystrophin. Here we report two unusual patients carrying nonsense mutations in the DMD gene and dystrophin deficiency but with an unexpectedly mild phenotype. Three reported polymorphisms, respectively in genes LTBP4, SPP1 and ACTN3 were excluded as possible DMD genetic modifiers in our patients. Finding the mechanisms that protect some rare patients and dogs from the deleterious effect of absent muscle dystrophin is of utmost importance and may lead to new avenues for treatment. Importantly, these observations indicate that it is possible to have a functional large muscle even without dystrophin. [ABSTRACT FROM AUTHOR]

During embryonic development, pluripotent cells are genetically committed to specific lineages by the expression of cell-type-specific transcriptional activators that direct the formation of specialized tissues and organs in response to developmental cues. Chromatin-modifying proteins are emerging as essential components of the epigenetic machinery, which establishes the nuclear landscape that ultimately determines the final identity and functional specialization of adult cells. Recent evidence has revealed that discrete populations of adult cells can retain the ability to adopt alternative cell fates in response to environmental cues. These cells include conventional adult stem cells and a still poorly defined collection of cell types endowed with facultative phenotype and functional plasticity. Under physiological conditions or adaptive states, these cells cooperate to support tissue and organ homeostasis, and to promote growth or compensatory regeneration. However, during chronic diseases and aging these cells can adopt a pathological phenotype and mediate maladaptive responses, such as the formation of fibrotic scars and fat deposition that progressively replaces structural and functional units of tissues and organs. The molecular determinants of these phenotypic transitions are only emerging from recent studies that reveal how dynamic chromatin states can generate flexible epigenetic landscapes, which confer on cells the ability to retain partial pluripotency and adapt to environmental changes. This review summarizes our current knowledge on the role of the epigenetic machinery as a 'filter' between genetic commitment and environmental signals in cell types that can alternatively promote skeletal muscle regeneration or fibro-adipogenic degeneration. [ABSTRACT FROM AUTHOR]

Abstract: In dystrophin-deficient fibers of mdx mice and in Duchenne muscular dystrophy, inflammation and increased production of tumor necrosis factor alpha (TNF-α) contribute to myonecrosis. We examined the effects of eicosapentaenoic acid (EPA) on dystrophic muscle degeneration. Mdx mice (14days old) received EPA for 16days. The sternomastoid, diaphragm and biceps brachii muscles were removed. Control mdx mice received vehicle. EPA decreased creatine kinase and myonecrosis and reduced the levels of TNF-α. These results suggest that EPA plays a protective role in dystrophic muscle degeneration, possibly by reducing TNF-α, and support further investigations of EPA as a potential therapy for dystrophinopathies. [Copyright &y& Elsevier]

Introduction: The development of a tracheo-arterial fistula is a rare but severe complication of tracheotomy. The reported patient presented with such a fistula involving an aberrant right subclavian artery, termed an arteria lusoria, an aortic arch abnormality which is usually asymptomatic. Case report: A 30-year-old man was admitted to our institution for bleeding through his tracheotomy. He had been treated for advanced Duchenne muscular dystrophy, involving invasive assisted ventilation, since the age of 10 years. Surgical exploration and computed tomography scanning revealed a tracheo-arterial fistula involving an aberrant right subclavian artery, associated with severe scoliosis. Emergency, transient haemostasis was achieved by over-inflation of the tracheostomy tube cuff. Aneurysm ablation was successfully achieved as the result of an endovascular interventional radiology procedure. Discussion: Arteria lusoria is one of the most common aortic arch abnormalities. The occurrence of an aneurysm of this artery in a tracheotomised patient has not previously been described. In Duchenne muscular dystrophy patients, spinal deformities may result in thoracic compression, which may alter the anatomical relations of mediastinal vessels. Such deformities are slowly progressive. Thus, vigilance is required in the long term management of Duchenne muscular dystrophy patients with a tracheostomy. [ABSTRACT FROM AUTHOR]

We have developed and characterized cultures of healthy and dystrophic canine myoblasts for the evaluation of various gene transfer protocols. The number of desmin-positive myoblasts was elevated (>>80%) in cultures of myoblasts obtained from different muscle territories, the diaphragm muscle giving rise to the purest cultures. Myoblasts from dogs turned out to be a very convenient source of well transfectable and transducible cells. Transfection with plasmid DNA allowed efficient transgene expression (50% of β-galactosidase positive cells and about 375 ng luciferase/mg protein after transfection with a calcium phosphate-precipitated plasmid). Infection with high concentrations of adenoviral and retroviral vectors allowed transgene (β-galactosidase or mini-dystrophin) detection in about 75 to 90% of the canine cells. Therefore, primary dog myoblast cultures represent a useful in vitro model for viral and non-viral gene delivery, as well as for functional evaluation and cell grafting with applications in genetic diseases, vaccination or production of circulating therapeutic proteins. [ABSTRACT FROM AUTHOR]

A total of 14 boys with the Duchenne and Becker forms of muscular dystrophy (DMD, BMD) were examined using P magnetic resonance (MR) spectroscopy; 12 boys were examined repeatedly. The results were correlated with clinical findings (including those of genetic tests) and with data obtained from examinations of an age-matched control group. Evaluation of results using principal component analysis revealed maximum variability in the following ratios: phosphocreatine/inorganic phosphate (PCr/Pi), phosphocreatine/phosphodiesters (PCr/PDe) and phosphocreatine/phosphomonoesters (PCr/PMe). A decrease in PCr/Pi correlates with weakness of the hip girdle and of the lower part of the shoulder girdle in DMD/BMD patients. The values of all ratios in the group of patients with the DMD phenotype differ significantly from results obtained in the group with the BMD phenotype. Continoous follow-up of patients using P MR spectroscopy revealed a marked decrease in PCr/Pi in DMD/BMD patients at an age that could be expected in subjects with a typical clinical course of DMD/BMD. An attempt to manage a concomitant disease with prednisone and carnitene was followed by an increase in PCr/Pi in 3 cases. A rise in the PCr/Pi ratio signalled clinical improvement in the patients. A decrease in PCr/Pi was found after controlled physical training, a finding consistent with data obtained from clinical observations describing an adverse effect of physical stress on the dystrophic process. [ABSTRACT FROM AUTHOR]

Copyright of Italian Journal of Neurological Sciences is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Neurology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Neurology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Neurology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cognitive profiles of 42 Italian school-age children with Duchenne muscular dystrophy were studied in relation to the site of mutations along the dystrophin gene, distal vs proximal, involving or sparing the expression of Dp140, respectively.