Aims: Regeneration in skeletal muscle relies on regulated myoblast migration and differentiation, in which the transcription factor nuclear factor of activated T-cells 5 (NFAT5) participates. Impaired muscle regeneration and chronic inflammation are prevalent in myositis. Little is known about the impact of inflammation on NFAT5 localization and expression in this group of diseases. The goal of this study was to investigate NFAT5 physiology in unaffected myoblasts exposed to cytokine or hyperosmolar stress and in myositis.Methods: NFAT5 intracellular localization and expression were studied in vitro using a cell culture model of myositis. Myoblasts were exposed to DMEM solutions enriched with pro-inflammatory cytokines IFN-γ with IL-1β or hyperosmolar DMEM obtained by NaCl supplementation. NFAT5 localization was visualized using immunohistochemistry (IHC) and Western blotting (WB) in fractionated cell lysates. NFAT5 expression was assessed by WB and RT-qPCR. In vivo localization and expression of NFAT5 were studied in muscle biopsies of patients diagnosed with polymyositis (n = 6), dermatomyositis (n = 10), inclusion body myositis (n = 11) and were compared to NFAT5 localization and expression in non-myopathic controls (n = 13). Muscle biopsies were studied by means of quantitative IHC and WB of total protein extracts.Results: In unaffected myoblasts, hyperosmolar stress ensues in NFAT5 nuclear translocation and increased NFAT5 mRNA and protein expression. In contrast, pro-inflammatory cytokines did not lead to NFAT5 nuclear translocation nor increased expression. Cytokines IL-1β with IFN-γ induced colocalization of NFAT5 with histone deacetylase 6 (HDAC6), involved in cell motility. In muscle biopsies from dermatomyositis and polymyositis patients, NFAT5 colocalized with HDAC6, while in IBM, this was often absent.Conclusions: Our data suggest impaired NFAT5 localization and expression in unaffected myoblasts in response to inflammation. This disturbed myogenic NFAT5 physiology could possibly explain deleterious effects on muscle regeneration in myositis.
Mobile WebpISSN 2093-4777 eISSN 2093-6931 INTERNATIONAL NEUROUROLOGY JOURNALPurpose: Clean intermittent self-catheterization (CISC) is now considered the gold standard for the management of urinary retention. In the literature, several articles on patients' perspectives on CISC and adherence to this technique have been published. No studies have yet explored the points of view of professional caregivers, such as nurses and doctors. The aim of this study was to explore the opinions of urologists about CISC and to evaluate the need for dedicated nurses specialized in CISC through a self-administered questionnaire. Methods: A questionnaire was developed to explore the opinions of professional caregivers about self-catheterization and to evaluate the need to provide nurses with specialized education in CISC. Questionnaires were sent to 244 urologists through email. We received 101 completed questionnaires. The response rate was 41.4%. Results: Hand function, the presence or absence of tremor, and visual acuity were rated as the most important determinants for proposing CISC to a patient. Twenty-five percent of the urologists reported that financial remuneration would give them a greater incentive to propose CISC. The lack of dedicated nurses was reported by half of the urologists as a factor preventing them from proposing CISC. A meaningful number of urologists thought that patients perceive CISC as invasive and unpleasant. Although most urologists would choose CISC as a treatment option for themselves, almost 1 urologist out of 5 would prefer a permanent catheter. Conclusions: This questionnaire gave valuable insights into urologists' perceptions of CISC, and could serve as the basis for a subsequent broader international study. Further research should also focus on the opinions of nurses and other caregivers involved in incontinence management. Apart from financial remuneration, it is also clear that ensuring sufficient expertise and time for high-quality CISC care is important. This could be a potential role for dedicated nurses.
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