Finite temperature effects on the structural stability of Si-doped HfO2_{2} using first-principles calculations

The structural stabilities of the monoclinic and tetragonal phases of Si-doped HfO$_{2}$ at finite temperatures were analyzed using a computational scheme to assess the effects of impurity doping. The finite temperature effects considered in this work represented lattice vibration and impurity configuration effects. The results show that 6% Si doping stabilizes the tetragonal phase at room temperature, although a higher concentration of Si is required to stabilize the tetragonal phase at zero temperature. These data indicate that lattice vibration and impurity configuration effects are important factors determining structural stability at finite temperatures.Comment: 5 pages, 3 figure

A multi-center study on low-frequency rTMS combined with intensive occupational therapy for upper limb hemiparesis in post-stroke patients

<p>Abstract</p> <p>Background</p> <p>Both low-frequency repetitive transcranial magnetic stimulation (rTMS) and intensive occupational therapy (OT) have been recently reported to be clinically beneficial for post-stroke patients with upper limb hemiparesis. Based on these reports, we developed an inpatient combination protocol of these two modalities for the treatment of such patients. The aims of this pilot study were to confirm the safety and feasibility of the protocol in a large number of patients from different institutions, and identify predictors of the clinical response to the treatment.</p> <p>Methods</p> <p>The study subjects were 204 post-stroke patients with upper limb hemiparesis (mean age at admission 58.5 ± 13.4 years, mean time after stroke 5.0 ± 4.5 years, ± SD) from five institutions in Japan. During 15-day hospitalization, each patient received 22 treatment sessions of 20-min low-frequency rTMS and 120-min intensive OT daily. Low-frequency rTMS of 1 Hz was applied to the contralesional hemisphere over the primary motor area. The intensive OT, consisting of 60-min one-to-one training and 60-min self-exercise, was provided after the application of low-frequency rTMS. Fugl-Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT) were performed serially. The physiatrists and occupational therapists involved in this study received training prior to the study to standardize the therapeutic protocol.</p> <p>Results</p> <p>All patients completed the protocol without any adverse effects. The FMA score increased and WMFT log performance time decreased significantly at discharge, relative to the respective values at admission (change in FMA score: median at admission, 47 points; median at discharge, 51 points; p < 0.001. change in WMFT log performance time: median at admission, 3.23; median at discharge, 2.51; p < 0.001). These changes were persistently seen up to 4 weeks after discharge in 79 patients. Linear regression analysis found no significant relationship between baseline parameters and indexes of improvement in motor function.</p> <p>Conclusions</p> <p>The 15-day inpatient rTMS plus OT protocol is a safe, feasible, and clinically useful neurorehabilitative intervention for post-stroke patients with upper limb hemiparesis. The response to the treatment was not influenced by age or time after stroke onset. The efficacy of the intervention should be confirmed in a randomized controlled study including a control group.</p

Long-term efficacy and safety of canagliflozin in combination with insulin in Japanese patients with type 2 diabetes mellitus

Aim: The aim of this study was to assess the long-term efficacy and safety of canagliflozin as add-on therapy in Japanese patients with type 2 diabetes mellitus who had inadequate glycaemic control with insulin. Materials and methods: The study comprised a 16-week, double-blind period in which patients were randomized to either placebo (P; N = 70) or canagliflozin (100 mg, CAN; N = 76), followed by a 36-week open-label period in which all patients received canagliflozin. The efficacy endpoints included the change in HbA1c from baseline to end of treatment. The safety endpoints were adverse events, hypoglycaemic events, and laboratory test values. Results: The changes from baseline (mean ± standard deviation, last observation carried forward) in the P/CAN and CAN/CAN groups, respectively, were −1.09% ± 0.85% and −0.88% ± 0.86% for HbA1c, −1.40% ± 2.54% and −2.14% ± 2.75% for body weight, and 7.84% ± 14.37% and 8.91% ± 10.80% for HOMA2-%B (all, P < .001). Adverse events occurred in 85.1% of the P/CAN group and 92.0% of the CAN/CAN group. Hypoglycaemic events occurred in 43.3% and 54.7%, respectively. All hypoglycaemic events were mild in severity and insulin dose reduction decreased the incidence rate of hypoglycaemic events. Post-hoc ordinal logistic modelling/logistic modelling showed that lower serum C-peptide at Week 0 was a risk factor for hypoglycaemia in both the P and CAN groups in the double-blind period as well as in the canagliflozin all-treatment period. Conclusions: This study demonstrates the long-term efficacy and safety of canagliflozin combined with insulin in Japanese patients

Anti-tumor effects of a nonsteroidal anti-inflammatory drug zaltoprofen on chondrosarcoma via activating peroxisome proliferator-activated receptor gamma and suppressing matrix metalloproteinase-2 expression.

金沢大学医薬保健研究域医学系Surgical resection is the only treatment for chondrosarcomas, because of their resistance to chemotherapy and radiotherapy; therefore, additional strategies are crucial to treat chondrosarcomas. Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor, which has been reported as a possible therapeutic target in certain malignancies including chondrosarcomas. In this study, we demonstrated that a nonsteroidal anti-inflammatory drug, zaltoprofen, could induce PPARγ activation and elicit anti-tumor effects in chondrosarcoma cells. Zaltoprofen was found to induce expressions of PPARγ mRNA and protein in human chondrosarcoma SW1353 and OUMS27 cells, and induce PPARγ-responsible promoter reporter activities. Inhibitory effects of zaltoprofen were observed on cell viability, proliferation, migration, and invasion, and the activity of matrix metalloproteinase-2 (MMP2); these effects were dependent on PPARγ activation and evidenced by silencing PPARγ. Moreover, we showed a case of a patient with cervical chondrosarcoma (grade 2), who was treated with zaltoprofen and has been free from disease progression for more than 2 years. Histopathological findings revealed enhanced expression of PPARγ and reduced expression of MMP2 after administration of zaltoprofen. These findings demonstrate that zaltoprofen could be a promising drug against the malignant phenotypes in chondrosarcomas via activation of PPARγ and inhibition of MMP2 activity. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.2957320

Development of an implicit method for directing weight shifting to the affected side in patients with stroke: a proof of concept study

Abstract Weight-shift training during stroke rehabilitation requires patient effort, potentially causing leg spasticity and anxiety, which disturb motor learning. The purpose of this study was (1) to devise an implicit guidance method for weight bearing that uses vibratory cues (and is therefore low exertion) and (2) to determine if the implicit guidance method is feasible. The first experiment included 12 healthy subjects. We conducted an experiment to produce a Weber’s fraction capable of calculating a just-noticeable difference during a weight-shifting task. We then applied this Weber’s fraction to a weight-shifting task in a patient with stroke. Using the implicit guidance method, the patient did not perceive an increase in weight bearing while weight shifting. Furthermore, the implicit guidance method appeared to reduce anxiety during training. This implicit guidance system warrants further investigation

Efficacy and safety of canagliflozin in combination with insulin: A double-blind, randomized, placebo-controlled study in Japanese patients with type 2 diabetes mellitus

Background: Combination therapy with canagliflozin and insulin was investigated in a prescribed substudy of the canagliflozin Cardiovascular Assessment Study (CANVAS); however, it was not evaluated in Japanese patients with type 2 diabetes mellitus (T2DM). Since the usage profile of insulin therapy and pathologic features of Japanese patients differ from those of Caucasian patients, we determined the clinical benefit of such a combination therapy in Japanese patients. Methods: Patients who had inadequate glycemic control despite insulin, diet and exercise therapies were randomized into placebo (n = 70) and canagliflozin 100 mg (n = 76) groups that were administered once daily in addition to their prior insulin therapy in this double-blind, placebo-controlled study. The primary endpoint was the change in glycated hemoglobin (HbA1c) levels from the baseline to week 16. Results: There was a statistically significant decrease in HbA1c levels from the baseline in the canagliflozin group ( 0.97 ± 0.08 %) compared with the placebo group (0.13 ± 0.08 %) at week 16 [last observation carried forward (LOCF)]. The decrease in HbA1c levels in the canagliflozin group was independent of the insulin regimen (premixed, long-acting and long-acting plus rapid- or short-acting). Compared with the placebo group, canagliflozin significantly decreased fasting plasma glucose levels (-34.1 ± 4.8 vs -1.4 ± 5.0 mg/dL) and body weights (-2.13 ± 0.25 vs 0.24 ± 0.26 %), and significantly increased HDL cholesterol (3.3 ± 1.0 vs -0.5 ± 1.0 mg/dL) and HOMA2- %B (10.15 ± 1.37 vs 0.88 ± 1.42 %). The overall incidence of adverse events was similar between the two groups. The incidence and incidence per subject-year exposure of hypoglycemia (hypoglycemic symptoms and/or decreased blood glucose) were slightly higher in the canagliflozin group (40.0 % and 7.97) than in the placebo group (29.6 % and 4.51). However, hypoglycemic events in both groups were mild in severity and dose-reduction of insulin by <10 % from the baseline following hypoglycemic events decreased the incidence per subject-year exposure in the canagliflozin group. The incidence of hypoglycemia between the groups did not differ according to the insulin regimen. Conclusion: Canagliflozin in combination with insulin was effective in improving glycemic control and reducing body weight and well tolerated by Japanese patients with T2DM. Trial Registration ClinicalTrials.gov identifier: NCT0222092