Objectives
This study aimed to evaluate the effectiveness of de-training after a combined intervention of leucine-enriched whey protein supplementation and resistance training on skeletal muscle mass ...and strength in older adults with sarcopenia.
Design
A randomized controlled trial.
Setting
A community in Hyogo, Japan.
Participants
The study included older adults aged ≥ 65 years who were screened for sarcopenia at the Care Center from, a community in Hyogo, Japan. The participants were randomly allocated to one of three groups: whey protein supplementation after resistance training (RT + PRO; n = 27), resistance training only (RT; n = 27), and whey protein supplementation only (PRO; n = 27).
Interventions
An intervention program was conducted over a period of 24 weeks. The program included RT and/or PRO supplementation twice a week for 24 weeks, followed by a de-training period for another 24 weeks. PRO supplementation included 11.0 g of protein and 2,300 mg of leucine. The total energy and protein intake amounts for the participants in all groups were controlled to achieve at least 30 kcal/kg ideal body weight (IBW)/day and 1.2 g/kg IBW/day, respectively, during the intervention and de-training periods.
Measurements
The primary outcomes, such as mean change of appendicular skeletal muscle mass index (ΔASMI), and secondary outcomes, such as handgrip strength (ΔHGS), were measured at baseline, the end of intervention, and at 12 and 24 weeks of de-training.
Results
Compared to baseline, ASMI and HGS increased significantly at the end of the intervention period in the RT+PRO group (ASMI and HGS, p < 0.01); however, there were no significant differences in ΔASMI and ΔHGS between each group. At 24 weeks of the de-training period, ΔASMI and ΔHGS were higher in the RT + PRO group than in the RT group (p < 0.05 and p < 0.01, respectively).
Conclusion
We demonstrated that combined intervention of RT and PRO showed long-term maintenance in treating sarcopenia than RT only at 24 weeks after de-training. Therefore, PRO intake after RT may be useful in the treatment of sarcopenia in older adults.
We investigate rates of pathologic complete response (pCR) and tumor expression of ER, PgR, HER2 discordance after neoadjuvant chemotherapy using Japanese breast cancer registry data.
Records of more ...than 300 000 breast cancer cases treated at 800 hospitals from 2004 to 2013 were retrieved from the breast cancer registry. After data cleanup, we included 21 755 patients who received neoadjuvant chemotherapy and had no distant metastases. pCR was defined as no invasive tumor in the breast detected during surgery after neoadjuvant chemotherapy. HER2 overexpression was determined immunohistochemically and/or using fluorescence in situ hybridization.
pCR was achieved in 5.7% of luminal tumors (n = 8730), 24.6% of HER2-positive tumors (n = 4403), and 18.9% of triple-negative tumors (n = 3660). Among HER2-positive tumors, pCR was achieved in 31.6% of ER-negative tumors (n = 2252), 17.0% of ER-positive ones (n = 2132), 31.4% of patients who received trastuzumab as neoadjuvant chemotherapy (n = 2437), and 16.2% of patients who did not receive trastuzumab (n = 1966). Of the 2811 patients who were HER2-positive before treatment, 601 (21.4%) had HER2-negative tumors after neoadjuvant chemotherapy, whereas 340 (3.4%) of the 9947 patients with HER2-negative tumors before treatment had HER2-positive tumors afterward. Of the 10 973 patients with ER-positive tumors before treatment, 499 (4.6%) had ER-negative tumors after neoadjuvant chemotherapy, whereas 519 (9.3%) of the 5607 patients who were ER-negative before treatment had ER-positive tumors afterward.
We confirmed that loss of HER2-positive status can occur after neoadjuvant treatment in patients with primary HER2-positive breast cancer. We also confirmed that in practice, differences in pCR rates between breast cancer subtypes are the same as in clinical trials. Our data strongly support the need for retest ER, PgR, HER2 of surgical sample after neoadjuvant therapy in order to accurately determine appropriate use of targeted therapy.
The local mechanical behavior near symmetric tilt grain boundaries in aluminum bicrystals were studied by the nanoindentation technique as well as by computer simulations. Experimentally, grain ...boundaries with misorientation angles 8.7°, 13.8° and 18.8° were examined. Two well pronounced pop-in events were observed on the load – penetration depth curves measured during indentation in the close vicinity of the studied boundaries. The load of the pop-ins, observed close to the boundaries, practically did not differ from that obtained in the grain interior. This was interpreted as evidence that the boundaries with misorientations in the examined angular range do not represent specific sites for sources of lattice dislocations. The load, at which the second pop-ins took place, substantially increased with increasing misorientation angle of the examined boundaries. Quasistatic molecular dynamics simulations were performed to identify the details of the interaction between grain boundary and dislocations generated during indentation. For this purpose, the bicrystals with similar geometry and misorientation angles, as investigated experimentally, were computed. The simulation results showed that the direct transmission of incoming dislocations across the grain boundary was the primary mechanism for the plastic flow transfer past the boundary. The analysis of the results of both experiments and simulations provided evidence that the capability of grain boundaries to act as a barrier for the motion of incoming dislocations depends crucially on grain boundary structure.
Summary
Although dysphagia is a life‐threatening problem in patients with Parkinson's disease (PD), the pathophysiology of oropharyngeal dysphagia is yet to be understood. This study investigated the ...tongue motor function during swallowing in relation to dysphagia and the severity of PD. Thirty patients with PD (14 males and 16 females; average age, 69.4 years), Hoehn and Yahr stage II‐IV, in Osaka University Hospital are participated in this study. During swallowing 5 ml of water, tongue pressure on the hard palate was measured using a sensor sheet with 5 measuring points. The maximal tongue pressure at each measuring point during swallowing was compared between patients with PD and healthy controls. Subjective assessment of oropharyngeal dysphagia was performed using Swallowing Disturbance Questionnaire‐Japanese. The maximal tongue pressure at each measuring point was significantly lower in patients with PD than in healthy controls (8 males and 12 females; average age, 71.6 years). Furthermore, the maximal tongue pressure was significantly lower in dysphagic PD patients than non‐dysphagic PD patients. Loss of tongue pressure production at the anterior part of the hard palate was strongly related to dysphagia in the oral phase as well as in the pharyngeal phase. An abnormal pattern of tongue pressure production was more frequently observed in dysphagic PD patients than in non‐dysphagic PD patients. The results suggest that tongue pressure measurement might be useful for early and quantitative detection of tongue motor disability during swallowing in patients with PD.
Abstract Metastatic melanoma is highly resistant to drug treatment, and the underlying mechanisms of this resistance remain unclear. Increased tissue stiffness is correlated with tumor progression, ...but whether increased tissue stiffness contributes to treatment resistance in melanoma is not known. To investigate the effect of substrate stiffness on melanoma cell treatment responsiveness, PEG hydrogels were utilized as a cell culture system to precisely vary matrix elasticity and investigate melanoma cell responses to a commercially available pharmacological inhibitor (PLX4032). The tensile moduli were varied between 0.6 and 13.1 kPa ( E ) and the effects of PLX4032 on metabolic activity, apoptosis, and proliferation were evaluated on human cell lines derived from radial growth phase (WM35) and metastatic melanoma (A375). The A375 cells were found to be stiffness-independent; matrix elasticity did not alter cell morphology or apoptosis with PLX4032 treatment. The WM35 cells, however, were more dependent on substrate modulus, displaying increased apoptosis and smaller focal adhesions on compliant substrates. Culturing melanoma cells on PEG hydrogels revealed stage-dependent responses to PLX4032 that would have otherwise been masked if cultured strictly on TCPS. These findings demonstrate the utility of PEG hydrogels as a versatile in vitro culture platform with which to investigate the molecular mechanisms of melanoma biology and treatment responsiveness.
COVID-19 vaccine hesitancy/fatigue is increasing as the pandemic enters the endemic phase. The present study aimed to explore current perceptions about COVID-19 booster vaccination among the Japanese ...public.
This was a cross-sectional study.
This cross-sectional study used data from the Japan COVID-19 and Society Internet Survey conducted in September 2021 and September 2022. The public's perceptions of COVID-19 vaccination and factors associated with COVID-19 booster vaccine hesitancy were analyzed.
In total, 56,735 respondents were included. In the Japan COVID-19 and Society Internet Survey 2021, 75.1% of the participants (21,126/28,118) had completed the primary vaccination series. In the 2022 survey, 74.1% of the respondents (21,216/28,617) completed the primary series of vaccination with booster doses. The proportion of fear toward COVID-19 and obtaining information about COVID-19 has decreased from 2021 to 2022. Factors independently associated with booster vaccine hesitancy were young age (range: 18–29 years; adjusted odds ratio aOR: 6.56), history of COVID-19 (aOR: 1.82), distrust of the Japanese government's COVID-19 prevention measures (aOR: 1.55), lack of confidence in COVID-19 vaccine efficacy (aOR: 1.30), lack of confidence in COVID-19 vaccine safety (aOR: 1.62), low reliance on the COVID-19 vaccine (aOR: 1.92), and belief in COVID-19 conspiracy theories (aOR: 1.77).
Providing clear and trustworthy information is critically important, especially targeted and tailored messages for the young generation, to promoting COVID-19 booster vaccination. Policymakers should therefore develop consistent and transparent communication strategies and the ability to respond promptly and flexibly to mitigate the negative impact of COVID-19 on the public while preparing for the next pandemic.
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