Although the cognitive impairment in Alzheimer’s disease (AD) is believed to be caused by amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs), several postmortem studies have reported cognitive normal subjects with AD brain pathology. As the mechanism underlying these discrepancies has not been clarified, we focused the neuroprotective role of astrocytes. After examining 47 donated brains, we classified brains into 3 groups, no AD pathology with no dementia (N-N), AD pathology with no dementia (AD-N), and AD pathology with dementia (AD-D), which represented 41%, 21%, and 38% of brains, respectively. No differences were found in the accumulation of Aβ plaques or NFTs in the entorhinal cortex (EC) between AD-N and AD-D. Number of neurons and synaptic density were increased in AD-N compared to those in AD-D. The astrocytes in AD-N possessed longer or thicker processes, while those in AD-D possessed shorter or thinner processes in layer I/II of the EC. Astrocytes in all layers of the EC in AD-N showed enhanced GLT-1 expression in comparison to those in AD-D. Therefore these activated forms of astrocytes with increased GLT-1 expression may exert beneficial roles in preserving cognitive function, even in the presence of Aβ and NFTs.
The aim of this study was to test the clinical utility of the 6-min walk test (6MWT) for patients with moderate Parkinson's disease (PD) through a determination of factors related to this test. This was a descriptive, observational study carried out at a General Hospital, in-patients. Twenty-four patients with moderate PD were studied. We used Hoehn and Yahr stage ratings (HY stage), Unified Parkinson Disease Rating Scales (UPDRS) motor examination score, 6MWT, Berg Balance scale, Timed 'Up & Go' test (TUG), 10-m walk test (10-m walk speed, 10-m walk steps and cadence), and the energy cost of walking (Ec). The average HY stage was 3.1±0.5 and 6MWT was 340.8±110.9 m. TUG (r=-0.68, P<0.01) and Ec (r=-0.65, P<0.01) were correlated significantly with 6MWT. Multiple regression analysis with age, HY stage, TUG, cadence, and Ec as variables indicated a significant degree of variability in the 6MWT results (R=0.77, P<0.001). The TUG (β=-0.47, P<0.01) and Ec (β=-0.4, P<0.01) were correlated independently with the 6MWT results. In contrast, age, HY stage, and cadence were not independently correlated. The 6MWT is a simple tool for assessing walking capacity for patients with PD. In this study, we confirmed the convergent validity and clinical utility of the 6MWT for patients with moderate PD. The 6MWT is useful for clinical assessment to guide the planning of rehabilitation treatment for patients with moderate PD.
The Japanese version of the MPOC has good psychometric properties and can be recommended for evaluation of the processes of child rehabilitation in Japan.
The MPOC-SP has good psychometric properties and can be used to identify areas for improvement in the family-centered care provided by multidisciplinary teams in the NICUs.
Background Preoperative chemotherapy is a promising strategy for downstaging advanced gastric cancer before radical resection, although severe adverse events can occur and clinical outcomes are often unsatisfactory. To identify predictive biomarkers of drug sensitivity, we used a welldesigned functional apoptosis assay and assessed the correlations between chemosensitivity and clinical outcomes. Methods Drug sensitivity to docetaxel, cisplatin, and 5-fluorouracil was examined in 11 gastric cancer cell lines. BCL2-homology domain 3 (BH3) profiling was performed and assessed for correlations with drug sensitivity. Immunohistochemical staining of clinical gastric cancer specimens was performed before preoperative chemotherapy, and correlations with histopathological responses and clinical outcomes were assessed. Results BIM (BCL2L11)-BH3 profiling results correlated with docetaxel sensitivity and BAK protein expression, whose knockdown caused docetaxel resistance. The BAK expression indexes of 69 gastric cancer specimens before preoperative chemotherapy (including docetaxel treatment) were determined by multiplying numerical values describing the degrees of BAK positivity and staining intensity observed. Patients whose specimens showed good chemotherapeutic histopathological responses had higher BAK indexes than those with poor responses. Patients with BAK index values C3 showed improved progression-free survival (HR, 2.664; 95 % CI, 1.352-5.248; P = 0.005) and overall survival (HR, 3.390; 95 % CI,; P = 0.002). Conclusions BH3 profiling clearly showed that BIM expression, which depends on BAK expression, correlated with docetaxel sensitivity. BAK expression in gastric cancer is thus predictive of chemotherapeutic responses to docetaxel and clinical prognosis in patients treated with preoperative chemotherapy.
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