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21.
M. V. Petkova A. Stantzou A. Morin O. Petrova S. Morales-Gonzalez F. Seifert J. Bellec-Dyevre T. Manoliu A. Goyenvalle L. Garcia I. Richard C. Laplace-Builhé M. Schuelke H. Amthor 《Neuropathology and applied neurobiology》2020,46(6):602-614
Background
Dmdmdx, harbouring the c.2983C>T nonsense mutation in Dmd exon 23, is a mouse model for Duchenne muscular dystrophy (DMD), frequently used to test therapies aimed at dystrophin restoration. Current translational research is methodologically hampered by the lack of a reporter mouse model, which would allow direct visualization of dystrophin expression as well as longitudinal in vivo studies.Methods
We generated a DmdEGFP-mdx reporter allele carrying in cis the mdx-23 mutation and a C-terminal EGFP-tag. This mouse model allows direct visualization of spontaneously and therapeutically restored dystrophin-EGFP fusion protein either after natural fibre reversion, or for example, after splice modulation using tricyclo-DNA to skip Dmd exon 23, or after gene editing using AAV-encoded CRISPR/Cas9 for Dmd exon 23 excision.Results
Intravital microscopy in anaesthetized mice allowed live-imaging of sarcolemmal dystrophin-EGFP fusion protein of revertant fibres as well as following therapeutic restoration. Dystrophin-EGFP-fluorescence persisted ex vivo, allowing live-imaging of revertant and therapeutically restored dystrophin in isolated fibres ex vivo. Expression of the shorter dystrophin-EGFP isoforms Dp71 in the brain, Dp260 in the retina, and Dp116 in the peripheral nerve remained unabated by the mdx-23 mutation.Conclusion
Intravital imaging of DmdEGFP-mdx muscle permits novel experimental approaches such as the study of revertant and therapeutically restored dystrophin in vivo and ex vivo.22.
The degree of upper extremity active range of motion provided by an admittance control robot compared with a commercially available passive arm support for individuals with DMD who have limited arm function was investigated in this study. The reachable workspace evaluation was used to assess active range of motion provided by both devices. A visual analog scale was also used to secure participant-reported outcome measures. The admittance control robot significantly increased reachable surface area scores compared with the passive arm support for the dominant arm (Wilcoxon T = 5, P = .022, r2 = 0.263) and for the nondominant arm (paired-samples t test, t(9) = 4.66, P = .001, r2 = 0.71). The admittance control robot also significantly decreased participant-reported exertion compared with the passive arm support. Results of this study substantiated the benefits of admittance control for individuals with DMD compared with a commercially available passive arm support. 相似文献
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Florian Barthelemy PhD Jeremy D. Woods MD Shirley Nieves-Rodriguez BS Emilie D. Douine MS Richard Wang PhD Jonathan Wanagat MD PhD M. Carrie Miceli PhD Stanley F. Nelson MD 《Muscle & nerve》2020,62(6):688-698
Serial muscle biopsies within clinical trials for Duchenne muscular dystrophy (DMD) are critical to document therapeutic responses. Less invasive means of sampling muscle are needed. We analyzed a retrospective consecutive case-series cohort of vacuum-assisted core needle muscle biopsy procedures performed on healthy and dystrophic individuals at a single institution assessing for safety and reliability of obtaining sufficient high-quality biopsy tissue for histologic assessment in adult and pediatric subjects. Of 471 muscle cores from 128 biopsy procedures, 377-550 mg of total muscle tissue was obtained per procedure with mean core weight of 129 mg (SD, 25.1 mg). All biopsies were adequate for histological assessment. There were no significant adverse events. This core needle biopsy approach, when combined with improved sample processing, provides a safe means to consistently obtain muscle samples for diagnostic and clinical trial applications. 相似文献
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Guillaume Parpex Marion Demouron Konstantinos Arapis Denis Chosidow Lionel Rebibo Simon Msika 《Clinical anatomy (New York, N.Y.)》2020,33(4):562-566
The sleeve gastrectomy (SG) can be performed with or without antral preservation (distance from the pylorus <50 mm). The objective of this study was to evaluate the distance between the pylorus and the end of the left vagus nerve in order to determine whether it could be used as a constant anatomical landmark to start gastric transection. This was a prospective, nonrandomized study of 120 patients undergoing SG from January to October 2018. The distance measurement between pylorus and vagus nerve was performed at the beginning of the SG. The primary endpoint was the distance between the beginning of the pylorus and the end of the second branch of the vagus nerve on the upper edge of the antrum. The secondary endpoints was the correlation factors between the preoperative data and the position of the end of the vagus nerve. A total of 120 patients, with a mean body mass index of 42.2 kg/m2, underwent primary SG. The mean distance between pylorus and the end of the vagus nerve was 50.4 mm (35–64) on the upper part of the antrum. When considering the inferior part of the antrum, the minimum distance was 50 mm. No correlations were found between preoperative data and distance measurements. The vagus nerve can be considered as a constant and reliable anatomical landmark for performing SG with antral preservation. However, no correlation was found between the preoperative data and the location of the end of the vagus nerve. Clin. Anat. 33:562–566, 2020. © 2019 Wiley Periodicals, Inc. 相似文献
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《Brain & development》2020,42(3):311-314
BackgroundIn July 2018, a rare and serious adverse effect (AE), namely, communicating hydrocephalus unrelated to meningitis or bleeding, was reported in relation to five patients treated with nusinersen for spinal muscular atrophy (SMA). Some patients were managed using a ventriculo-peritoneal shunt (VPS) implant and continued to receive nusinersen treatment. However, there is limited information concerning the effectiveness and safety of nusinersen treatment for patients with a VPS.Case reportA female patient exhibited general hypotonia soon after birth and was diagnosed, using genetic analysis, with spinal muscular atrophy. She required permanent invasive ventilation from 2 months of age. She developed a progressive hydrocephalus and underwent placement of a VPS in infancy. Treatment with nusinersen was initiated when she was 7 years old. The neurofilament light-chain (NfL) concentration in the cerebrospinal fluid (CSF) decreased over time with nusinersen treatment. Twelve months have passed since the start of nusinersen treatment and no AEs have been observed.ConclusionNusinersen treatment may be effective and safe, even after placement of a VPS. NfL levels in the CSF could be valuable markers of disease activity/treatment response even in advanced stages of SMA. 相似文献
28.
Sarcoglycanopathies are a genetically heterogeneous group of autosomal recessive limb-girdle muscular dystrophies (LGMD) caused by mutations in sarcoglycan genes. We report a Portuguese patient with a very late-onset LGMD phenotype, whose muscle biopsy and immunostaining, in particular for α-sarcoglycan, were unrevealing. Muscle MRI showed a predominant, bilateral and symmetric involvement of the tight muscles and also, to a lesser extent, of the posterior compartment of lower legs muscles. Next generation sequencing (NGS) revealed a known homozygous c.850C > T (p.Arg284Cys) mutation in SGCA gene. Milder forms of α-sarcoglycanopathies could be a challenging diagnosis; particularly if muscle histopathology and α-sarcoglycan immunohistochemistry are unhelpful. NGS plays a crucial role not only for aiding in the establishment of a definite diagnosis, but also for expanding clinical presentations. 相似文献
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