Search results for: lean body matrix

Authors: Leila Noori, Rosario Barone, Francesca Rappa, Antonella Marino Gammazza, Alessandra Maria Vitale, Giuseppe Donato Mangano, Giusy Sentiero, Filippo Macaluso, Kathryn H. Myburgh, Francesco Cappello, Federica Scalia

Abstract:

The neuromuscular system controls, directs, and allows movement of the body through the action of neural circuits, which include motor neurons, sensory neurons, and skeletal muscle fibers. Protein homeostasis of the involved cytotypes appears crucial to maintain the correct and prolonged functions of the neuromuscular system, and both neuronal cells and skeletal muscle fibers express significant quantities of protein chaperones, the molecular machinery responsible to maintain the protein turnover. Genetic mutations or defective post-translational modifications of molecular chaperones (i.e., genetic or acquired chaperonopathies) may lead to neuromuscular disorders called as neurochaperonopathies. The limited knowledge of the effects of the defective chaperones on skeletal muscle fibers and neurons impedes the progression of therapeutic approaches. A distinct genetic variation of CCT5 gene encoding for the subunit 5 of the chaperonin CCT (Chaperonin Containing TCP1; also known as TRiC, TCP1 Ring Complex) was recently described associated with severe distal motor neuropathy by our team. In this study, we investigated the histopathological abnormalities of the skeletal muscle biopsy of the pediatric patient affected by the mutation Leu224Val in the CCT5 subunit. We provide molecular and structural features of the diseased skeletal muscle tissue that we believe may be useful to identify undiagnosed cases of this rare genetic disorder. We investigated the histological abnormalities of the affected tissue via hematoxylin and eosin staining. Then we used immunofluorescence and qPCR techniques to explore the expression and distribution of CCT5 in diseased and healthy skeletal muscle tissue. Immunofluorescence and immunohistochemistry assays were performed to study the sarcomeric and structural proteins of skeletal muscle, including actin, myosin, tubulin, troponin-T, telethonin, and titin. We performed Western blot to examine the protein expression of CCT5 and some heat shock proteins, Hsp90, Hsp60, Hsp27, and α-B crystallin, along with the main client proteins of the CCT5, actin, and tubulin. Our findings revealed muscular atrophy, abnormal morphology, and different sizes of muscle fibers in affected tissue. The swollen nuclei and wide interfiber spaces were seen. Expression of CCT5 had been decreased and showed a different distribution pattern in the affected tissue. Altered expression, distribution, and bandage pattern were detected by confocal microscopy for the interested muscular proteins in tissue from the patient compared to the healthy control. Protein levels of the studied Hsps normally located at the Z-disk were reduced. Western blot results showed increased levels of the actin and tubulin proteins in the diseased skeletal muscle biopsy compared to healthy tissue. Chaperones must be expressed at high levels in skeletal muscle to counteract various stressors such as mechanical, oxidative, and thermal crises; therefore, it seems relevant that defects of molecular chaperones may result in damaged skeletal muscle fibers. So far, several chaperones or cochaperones involved in neuromuscular disorders have been defined. Our study shows that alteration of the CCT5 subunit is associated with the damaged structure of skeletal muscle fibers and alterations of chaperone system components and paves the way to explore possible alternative substrates of chaperonin CCT. However, further studies are underway to investigate the CCT mechanisms of action to design applicable therapeutic strategies.

Keywords: molecular chaperones, neurochaperonopathy, neuromuscular system, protein homeostasis

Procedia PDF Downloads 56

Authors: Tianqiao Zhang, Ye Tian, Yanliang Yin, Yichao Tian, Suzhai Tian, Weige Sun, Shuhui Gong, Limei Tang, Ruoliang Tang

Abstract:

Introduction: Healthcare workers, especially the nurses all over the world, are highly vulnerable to work-related musculoskeletal disorders (WMSDs), experiencing high rates of neck, shoulder, and low back injuries, due to the unfavorable working conditions. To reduce WMSDs among nursing personnel, many workplace interventions have been developed and implemented. Unfortunately, the ongoing Covid-19 (SARS-CoV-2) pandemic has posed great challenges to the ergonomic practices and interventions in healthcare facilities, particularly the hospitals, since current Covid-19 mitigation measures, such as social distancing and working remotely, has substantially minimized in-person gatherings and trainings. On the other hand, hospitals throughout the world have been short-staffed, resulting in disturbance of shift scheduling and more importantly, the increased job demand among the available caregivers, particularly the doctors and nurses. With the latest development in communication technology, remote intervention measures have been developed as an alternative, without the necessity of in-person meetings. The Omaha System (OS) is a standardized classification system for nursing practices, including a problem classification system, an intervention system, and an outcome evaluation system. This paper describes the development of an OS-based ergonomic intervention program. Methods: First, a comprehensive literature search was performed among worldwide electronic databases, including PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), between journal inception to May 2020, resulting in a total of 1,418 scientific articles. After two independent screening processes, the final knowledge pool included eleven randomized controlled trial studies to develop the draft of the intervention program with Omaha intervention subsystem as the framework. After the determination of sample size needed for statistical power and the potential loss to follow-up, a total of 94 nurses from eight clinical departments agreed to provide written, informed consent to participate in the study, which were subsequently assigned into two random groups (i.e., intervention vs. control). A subgroup of twelve nurses were randomly selected to participate in a semi-structured interview, during which their general understanding and awareness of musculoskeletal disorders and potential interventions was assessed. Then, the first draft was modified to reflect the findings from these interviews. Meanwhile, the tentative program schedule was also assessed. Next, two rounds of consultation were conducted among experts in nursing management, occupational health, psychology, and rehabilitation, to further adjust and finalize the intervention program. The control group had access to all the information and exercise modules at baseline, while an interdisciplinary research team was formed and supervised the implementation of the on-line intervention program through multiple social media groups. Outcome measures of this comparative study included biomechanical load assessed by the Quick Exposure Check and stresses due to awkward body postures. Results and Discussion: Modification to the draft included (1) supplementing traditional Chinese medicine practices, (2) adding the use of assistive patient handling equipment, and (3) revising the on-line training method. Information module should be once a week, lasting about 20 to 30 minutes, for a total of 6 weeks, while the exercise module should be 5 times a week, each lasting about 15 to 20 minutes, for a total of 6 weeks.

Keywords: ergonomic interventions, musculoskeletal disorders (MSDs), omaha system, nurses, Covid-19

Procedia PDF Downloads 152