Test-retest reliability was moderate to excellent (ICC's ranging from .78 to .91) with a trend towards better performance on retest. The ESTCS increased sample size and drop-out rate up to 100 and 85%. CONCLUSIONS Fatigability is an important additional dimension of physical impairments across the severity spectrum in children and adults with SMA. The EST's are reliable and valid to document fatigability of walking, proximal- and distal arm function in SMA and thus are promising outcome measures for use in clinical trials.BACKGROUND Currently available procedures for the treatment of minimally displaced acetabular fractures include conservative treatment and minimally invasive percutaneous screw fixation. Screw fixation of acetabular fractures allows patients' early full-weight bearing due to improved biomechanic stability. Can the range of motion, pain and mobility and quality of life in patients with acetabular fractures be improved by minimally invasive screw fixation, compared to conservative treatment in the long term? METHODS Patients treated for a minimally displaced acetabular fracture, either conservatively or by closed reduction percutaneous screw fixation, in the period from 2001 to 2013 were included in this retrospective study. Minimal displacement was considered to be less than 5 mm. As well as the collection and analysis of baseline data, Harris Hip Score, Merle d'Aubigné score and Short Form 12 (SF-12) questionnaire data were recorded in the context of a clinical study. To better account for confounding factorsctures. Prospective randomised studies are recommended to allow reliable evaluation of both treatment options. TRIAL REGISTRATION Retrospectively registered.BACKGROUND The histone methyltransferase G9a has recently been identified as a potential target for epigenetic therapy of acute myeloid leukemia (AML). However, the effect of G9a inhibition on leukemia stem cells (LSCs), which are responsible for AML drug resistance and recurrence, is unclear. In this study, we investigated the underlying mechanisms of the LSC resistance to G9a inhibition. METHODS We evaluated the effects of G9a inhibition on the unfolded protein response and autophagy in AML and LSC-like cell lines and in primary CD34+CD38- leukemic blasts from patients with AML and investigated the underlying mechanisms. The effects of treatment on cells were evaluated by flow cytometry, western blotting, confocal microscopy, reactive oxygen species (ROS) production assay. RESULTS The G9a inhibitor BIX-01294 effectively induced apoptosis in AML cell lines; however, the effect was limited in KG1 LSC-like cells. BIX-01294 treatment or siRNA-mediated G9a knockdown led to the activation of the PERK/NRF2 pathway to G9a inhibition and eliminate LSCs, suggesting the potential clinical utility of these unique targeted therapies against AML.BACKGROUND Epithelial ovarian cancer (EOC) is a highly lethal malignancy. Improvement in genetic characterization of EOC patients is required to propose new potential targets, since surgical resection coupled to chemotherapy, presents several limits such as cancer recurrence and drug resistance. Targeted therapies have more efficacy and less toxicity than standard treatments. One of the most relevant cancer-specific actionable targets are protein tyrosine kinases (PTKs) whose role in EOC need to be better investigated. METHODS EOC genomic datasets are retrieved and analyzed. The biological and clinical significance of RET genomic aberrations in ovarian cancer context are investigated by a series of in vitro and in vivo experiments. RESULTS Epithelial ovarian cancer sequencing projects identify recurrent genomic RET missense mutations in 1.98% of patients, ranking as the top-five hit among the 100 receptor tyrosine kinases-encoding genes. RET mutants R693H and A750T show oncogenic transformation properties in NIH3T3 cells. Introduction of the RET mutants into human EOC cells increases RET signaling, cell viability, anchorage-independent cell growth and tumor xenograft growth in nude mice, demonstrating that they are activating mutations. RET mutants significantly enhance the activation of RET and its downstream MAPK and AKT signaling pathway in ovarian cancer cells. Vandetanib, a clinical approved RET inhibitor, inhibits the cell viability and decreases the activation of RET-MAPK signaling pathways in EOC cells expressing oncogenic RET mutants.  https://www.selleckchem.com/products/zidesamtinib.html  CONCLUSIONS The discovery of RET pathogenic variants in the EOC patients, suggests a previously underestimated role for RET in EOC tumorigenesis. The identification of the gain-of-function RET mutations in EOC highlights the potential use of RET in targeted therapy to treat ovarian cancer patients.BACKGROUND Rheumatoid arthritis (RA), a kind of autoimmune disorder, is featured by many physical symptoms and proliferation of fibroblast-like synoviocytes (FLSs). The relevance of long non-coding RNAs (lncRNAs) in the progression of RA has been probed. Hence, the goal of this report was to investigate the action of plasmacytoma variant translocation 1 (PVT1), a lncRNA, in FLSs and the basic mechanism. METHODS Initially, RA rats were developed to evaluate the expression of PVT1, microRNA-543 (miR-543), and signal peptide-CUB-EGF-like containing protein 2 (SCUBE2) in synovial tissues. Enhancement or loss of PVT1 or miR-543 was achieved to explore their effects on proliferation, cell cycle, and apoptosis of FLSs. The interaction between PVT1 and miR-543 and between miR-543 and its putative target SCUBE2 was examined to elucidate the correlations. Finally, the protein expression of proliferation- and apoptosis-associated genes were assessed by western blot assays. RESULTS PVT1 was overexpressed in synovial tissues from RA patients through microarray expression profiles. The PVT1 and SCUBE2 expression was boosted, and miR-543 was reduced in synovial tissues of rats with RA. PVT1 specifically bound to miR-543, and miR-543 negatively regulated SCUBE2 expression. Overexpression of PVT1 or silencing of miR-543 enhanced SCUBE2 expression, thereby promoting proliferation and interleukin-1β (IL-1β) secretion, while inhibiting apoptosis rate of FLSs. Conversely, si-SCUBE2 reversed the role of miR-543 inhibitor. CONCLUSION The key findings support that PVT1 knockdown has the potency to hinder RA progression by inhibiting SCUBE2 expression to sponge miR-543.