RESUMEN
Wearable devices for the quantification of walking have recently been adopted for gait rehabilitation. To apply this method in subacute rehabilitation settings, this approach must be effective in these populations and implemented as a feasible method in terms of adherence and safety, especially the risk of falling. This study aimed to investigate the feasibility and efficacy of an activity monitoring approach in subacute rehabilitation using a commercially available pedometer validated with slow walking. This randomized controlled study with blinded assessors recruited 29 patients admitted to a rehabilitation ward. The participants were randomly assigned to either the feedback (intervention) or the no-feedback (control) group. Participants in both groups received at least 120â min of therapy sessions every day for 6 or 7 days per week while wearing pedometers on their unaffected ankles from the day they were permitted to walk independently till discharge. Only participants in the feedback group received weekly encouragement and the next goals. The primary outcome was the change in the 6-minute walking distance (Δ6MD). Feasibility (percentage of pedometer data acquisition days in the total observational period and the number of falls) and other efficacy outcomes (step counts, gait speed, 30-seconds chair stand test, Berg Balance Scale, and Timed Up and Go Test) were also evaluated. Regarding feasibility outcomes, the data acquisition rate was 94.1% and the number of falls during the observation period was one in the feedback group. Regarding efficacy outcomes, Δ6MD was not significantly greater in the feedback group [mean (standard deviation): 79.1 (51.7) m] than in the no-feedback group [86.1 (65.4) m] (p = 0.774) and the other five secondary outcomes showed no between-group difference. Considering the large number of steps per day in both groups [6,912 (4,751) and 5,600 (5,108) steps in the feedback and no-feedback group, respectively], the effect of the intended intervention might have been masked by the effect of simply wearing pedometers in the control group. This study revealed that the activity monitoring approach using an ankle-worn pedometer was practical in terms of adherence and safety. Further clinical trials are required to elucidate ways to effectively use wearable devices in subacute rehabilitation.
RESUMEN
The Goto-Kakizaki (GK) rat is a spontaneous animal model of type 2 diabetes and early stage of diabetic nephropathy. However, the pathophysiological mechanisms contributing to the progression of diabetic nephropathy in GK rats remain unclear. Kidneys from 15-week old male diabetic GK/Jcl rats and age-matched Wistar rats, which have the same genetic background as GK rats, were used. Proteomic analyses of GK and Wistar kidneys were performed using two-dimensional fluorescence difference gel electrophoresis (2D-DIGE). Differentially expressed proteins in GK rats were subjected to pathway analysis, and expression levels of hypoxia inducible factor 1α (HIF-1α) and transforming growth factor-ß1 (TGF-ß1), and fumarate accumulation in GK kidneys were examined. Azan staining and immunohistochemical staining of α-smooth muscle actin were performed in relation to fibrosis in GK kidneys. Proteomic analysis using 2D-DIGE, analysis of fumarate content, and expression analysis of HIF-1α, TGF-ß1, and α-smooth muscle actin of GK rat's kidney, suggested the mechanism of fibrosis characterized as two stages in diabetic nephropathy of GK rats. Abnormalities of glucose metabolism such as elevated levels of 2-oxoglutarate dehydrogenase and reduction of fumarate hydratase caused the accumulation of fumarate followed by the upregulation of HIF-1α and TGF-ß1 leading to fibrosis in diabetic nephropathy. Alterations in proteins involved in the tricarboxylic acid cycle are associated with fibrosis through fumarate accumulation in diabetic nephropathy of GK rats.
Asunto(s)
Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Fumaratos/metabolismo , Riñón/patología , Animales , Ciclo del Ácido Cítrico , Regulación hacia Abajo , Fibrosis , Masculino , RatasRESUMEN
BAG-6/Scythe/BAT3 is a ubiquitin-like protein that was originally reported to be the product of a novel gene located within the human major histocompatibility complex, although the mechanisms of its function remain largely obscure. Here, we demonstrate the involvement of BAG-6 in the degradation of a CL1 model defective protein substrate in mammalian cells. We show that BAG-6 is essential for not only model substrate degradation but also the ubiquitin-mediated metabolism of newly synthesized defective polypeptides. Furthermore, our in vivo and in vitro analysis shows that BAG-6 interacts physically with puromycin-labeled nascent chain polypeptides and regulates their proteasome-mediated degradation. Finally, we show that knockdown of BAG-6 results in the suppressed presentation of MHC class I on the cell surface, a procedure known to be affected by the efficiency of metabolism of defective ribosomal products. Therefore, we propose that BAG-6 is necessary for ubiquitin-mediated degradation of newly synthesized defective polypeptides.