Japan's population is aging more rapidly than that of any other country. Frailty has recently been recognized as an important priority. Understanding the basic epidemiology of frailty in Japan, which ...is an example of a rapidly aging society, will be beneficial for Japan as well as other countries expecting an aging population. A systematic literature search of 11 electronic databases was conducted in March 2016 using a comprehensive set of Medical Subject Heading and text terms for any studies published in 2000 or later that report the prevalence of frailty among Japanese community-dwelling older people aged 65 years or older. A total of 1529 studies were identified in the systematic search, of which five studies were included in this review. The pooled prevalence of frailty, prefrailty, and robustness was 7.4% (95% confidence interval CI, 6.1%–9.0%), 48.1% (95% CI, 41.6%–54.8%), and 44.4% (95% CI, 37.2%–51.7%), respectively. A significant degree of heterogeneity was observed. There was no evidence of publication bias. Age-stratified meta-analyses of four studies showed the pooled prevalence of frailty was 1.9%, 3.8%, 10.0%, 20.4%, and 35.1% for those aged 65–69, 70–74, 75–79, 80–84, and ≥85 years, respectively. Pooled prevalence of frailty was 8.1% for women and 7.6% for men. This review showed an overall pooled prevalence of frailty among Japanese community-dwelling older people of 7.4%. The age-stratified analysis suggested that Japanese older people are less frail before their late 70's but frailer in later life than older people in other countries. These findings provide important basic information for all parties involved in Japanese frailty research.
•Frailty is an important priority in Japan, where the population is aging rapidly.•Japan is a good example of a rapidly aging society for frailty research.•Five studies were included in this systematic review and meta-analysis study.•Pooled prevalence of frailty in Japanese in the community aged >65 years is 7.4%.
Distribution of relaxation times (DRT) analysis is a powerful assistant tool for electrochemical impedance spectroscopy (EIS) deconvolution. In the present work, electrode degradation is evaluated by ...estimation of polarization resistances using DRT analysis. Five or six DRT peaks are detected for anode-supported microtubular solid oxide fuel cells (SOFCs) at 600–650 °C. In a reduction-oxidation (redox) cycling test, the polarization resistance of charge transfer and ionic conduction processes in the anode increases due to the decrease in triple phase boundary (TPB) length. On the other hand, initial electrode degradation is also successfully evaluated using DRT analysis during a galvanostatic test. The rapid growth of nickel grains in the anode and the relatively slow growth of La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) grains in the cathode are observed after the test, which corresponds with the increase in the polarization resistance of charge transfer and ionic conduction processes in the anode and that of oxygen surface exchange and diffusion processes in the cathode, respectively.
The ability to utilize preclinical models to predict the clinical toxicity of chimeric antigen receptor (CAR) T cells in solid tumors is tenuous, thereby necessitating the development and evaluation ...of gated systems. Here we found that murine GD2 CAR-T cells, specific for the tumor-associated antigen GD2, induce fatal neurotoxicity in a costimulatory domain-dependent manner. Meanwhile, human B7H3 CAR-T cells exhibit efficacy in preclinical models of neuroblastoma. Seeking a better CAR, we generated a SynNotch gated CAR-T, GD2-B7H3, recognizing GD2 as the gate and B7H3 as the target. GD2-B7H3 CAR-T cells control the growth of neuroblastoma in vitro and in metastatic xenograft mouse models, with high specificity and efficacy. These improvements come partly from the better metabolic fitness of GD2-B7H3 CAR-T cells, as evidenced by their naïve T-like post-cytotoxicity oxidative metabolism and lower exhaustion profile.
Gait speed in laboratory settings (in-laboratory gait speed) is one of the important indicators associated with the decline in functional abilities in older adulthood. Recently, it has become ...possible to measure gait speed during daily living (daily gait speed) using accelerometers. However, the relationship between these two gait speed parameters is unclear. This study aimed to compare in-laboratory gait speed, measured by a sheet-type pressure sensor, and daily gait speed, measured by an accelerometer, in healthy community-dwelling older adults. Participants were aged ≥60 years, residing in Takahama city, Aichi, Japan. To calculate daily gait speed, participants were instructed to wear a tri-axial accelerometer on their waist. A total of 1965 participants were included in the final analysis. The results showed a weak association (r = 0.333, p < 0.001) between the two gait speed parameters. Furthermore, average daily gait speed was significantly lower than average in-laboratory gait speed. However, both gait speed parameters declined significantly with age. These results suggest that, in addition to in-laboratory gait speed, daily gait speed may be a helpful parameter for predicting decline in functional abilities.
Alzheimer's disease is believed to begin with synaptic dysfunction caused by soluble Aβ oligomers. When this oligomer hypothesis was proposed in 2002, there was no direct evidence that Aβ oligomers ...actually disrupt synaptic function to cause cognitive impairment in humans. In patient brains, both soluble and insoluble Aβ species always coexist, and therefore it is difficult to determine which pathologies are caused by Aβ oligomers and which are caused by amyloid fibrils. Thus, no validity of the oligomer hypothesis was available until the Osaka mutation was discovered. This mutation, which was found in a Japanese pedigree of familial Alzheimer's disease, is the deletion of codon 693 of APP gene, resulting in mutant Aβ lacking the 22nd glutamate. Only homozygous carriers suffer from dementia. In vitro studies revealed that this mutation has a very unique character that accelerates Aβ oligomerization but does not form amyloid fibrils. Model mice expressing this mutation demonstrated that all pathologies of Alzheimer's disease can be induced by Aβ oligomers alone. In this review, we describe the story behind the discovery of the Osaka mutation, summarize the mutant's phenotypes, and propose a mechanism of its recessive inheritance.
Abstract
Solid oxide fuel cells (SOFCs) are power-generating devices with high efficiencies and considered as promising alternatives to mitigate energy and environmental issues associated with fossil ...fuel technologies. Nanoengineering of electrodes utilized for SOFCs has emerged as a versatile tool for significantly enhancing the electrochemical performance but needs to overcome issues for integration into practical cells suitable for widespread application. Here, we report an innovative concept for high-performance thin-film cathodes comprising nanoporous La
0.6
Sr
0.4
CoO
3
−
δ
cathodes in conjunction with highly ordered, self-assembled nanocomposite La
0.6
Sr
0.4
Co
0.2
Fe
0.8
O
3
−
δ
(lanthanum strontium cobalt ferrite) and Ce
0.9
Gd
0.1
O
2
−
δ
(gadolinia-doped ceria) cathode layers prepared using pulsed laser deposition. Integration of the nanoengineered cathode layers into conventional anode-supported cells enabled the achievement of high current densities at 0.7 V reaching ~2.2 and ~4.7 A/cm
2
at 650 °C and 700 °C, respectively. This result demonstrates that tuning material properties through an effective nanoengineering approach could significantly boost the electrochemical performance of cathodes for development of next-generation SOFCs with high power output.
Objectives
To determine the standard values of and age‐related changes in objective oral function of healthy older people; compare oral function of robust, prefrail, and frail older people; and ...determine the association between oral function and frailty.
Design
Cross‐sectional analysis.
Setting
General community.
Participants
Elderly adults (≥65) from the Obu Study of Health Promotion for the Elderly were included and assigned to the robust, prefrail, and frail groups (N = 4,720).
Measurements
Each participant underwent detailed physical testing to assess frailty. The frailty phenotype was defined according to the presence of limitations in three or more of the following five domains: mobility, strength, endurance, physical activity, and nutrition. The numbers of present teeth and functional teeth were counted, and occlusal force, masseter muscle thickness, and oral diadochokinesis (ODK) rate were measured, along with sociodemographic and functional status, comorbidities, and blood chemistry.
Results
The number of present teeth, occlusal force, masseter muscle thickness, and ODK rate decreased with age. The frail group had significantly fewer present teeth (women aged ≥70), lower occlusal force (women aged ≥70; men aged ≥80), lower masseter muscle thickness, and lower ODK rate than the robust group. Multivariate analysis indicated that age, Geriatric Depression Scale score, skeletal muscle mass index, Mini‐Mental State Examination score, hypertension, diabetes mellitus, albumin and triglyceride levels, and oral function were significantly associated with frailty.
Conclusion
Age‐related differences in oral function were found in older adults. Moreover, frail older individuals had significantly poorer oral function than prefrail and robust individuals. The risk of frailty was associated with lower occlusal force, masseter muscle thickness, and ODK rate.
ObjectiveTo examine the relationship between physical frailty and risk of disability, and to identify the component(s) of frailty with the most impact on disability in community-dwelling older ...adults.DesignProspective cohort study.SettingA Japanese community.Participants4341 older adults aged ≥65 living in the community participated in a baseline assessment from 2011 to 2012 and were followed for 2 years.Main outcome measuresCare-needs certification in the national long-term care insurance (LTCI) system of Japan, type of physical frailty (robust, prefrail, frail) and subitems (slowness, weakness, exhaustion, low activity, weight loss), adjusted for several potential confounders such as demographic characteristics, analysed with Kaplan-Meier survival curves for incidence of disability by frailty phenotype.ResultsDuring the 2-year follow-up period, 168 participants (3.9%) began using the LTCI system for incidence of disability. Participants classified as frail (HR 4.65, 95% CI 2.63 to 8.22) or prefrail (2.52, 1.56 to 4.07) at the baseline assessment had an increased risk of disability incidence compared with robust participants. Analyses for subitems of frailty showed that slowness (2.32, 1.62 to 3.33), weakness (1.90, 1.35 to 2.68) and weight loss (1.61, 1.13 to 2.31) were related to increased risk of disability incidence. In stratified analyses, participants who were classified as frail and who had lower cognitive function had the highest percentage (30.3%) of disability incidence during the 2 years after baseline assessment.ConclusionsPhysical frailty, even being prefrail, had a strong impact on the risk of future disability. Some components of frailty, such as slowness, weakness and weight loss, are strongly associated with incident disability in community-dwelling older adults.
Protonic ceramic fuel cells (PCFCs) are expected to achieve high power generation efficiency at intermediate temperature around 400-600 °C. In the present work, the distribution of relaxation times ...(DRT) analysis was investigated in order to deconvolute the anode and cathode polarization resistances for PCFCs supported on yttria-doped barium cerate (BCY) electrolyte in comparison with solid oxide fuel cells (SOFCs) supported on scandia-stabilized zirconia (ScSZ) electrolyte. Four DRT peaks were detected from the impedance spectra measured at 700 °C excluding the gas diffusion process for ScSZ and BCY. The DRT peaks at 5 × 10
-1 × 10
Hz and 1 × 10
-2 × 10
Hz were related to the hydrogen oxidation reaction at the anode and the oxygen reduction reaction at the cathode, respectively, for both cells. The DRT peak at 2 × 10
-1 × 10
Hz depended on the hydrogen concentration at the anode for ScSZ, while it was dependent on the oxygen concentration at the cathode for BCY. Compared to ScSZ, steam was produced at the opposite electrode in the case of BCY, which enhanced the cathode polarization resistance for PCFCs.
Although previous studies have revealed many factors related to mild cognitive impairment (MCI) reversion, information about reversible factors related MCI reversion is limited, impeding the ...development of intervention strategies. The aim of the present study was to examine whether reversible factors such as lifestyle activities are associated with MCI reversion in elderly individuals using the National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes database. A total of 396 community-living older adults (age ≥ 65 years) participated in the study. They were classified as reverters or non-reverters from mild cognitive impairment to normal cognition. We assessed lifestyle activities, potential confounding factors of cognitive decline, and reversion of mild cognitive impairment.
In a completed data set of 396 participants, 202 participants (51.0%) reverted from MCI to normal cognition. The reversion rate in participants for whom we imputed data was 34.3%. In the imputed group, a logistic regression model showed that the odds ratios (ORs) for reversion were significantly higher in participants who drove a car (OR 1.50, 95% confidence interval (CI) 1.41-1.60), used a map to travel to unfamiliar places (OR 1.12, 95% CI 1.06-1.18), read books or newspapers (OR 1.54, 95% CI 1.37-1.73), took cultural classes (OR 1.10, 95% CI 1.04-1.15), attended meetings in the community (OR 1.22, 95% CI 1.16-1.28), participated in hobbies or sports activities (OR 1.09, 95% CI 1.03-1.16), and engaged in fieldwork or gardening (OR 1.14, 95% CI 1.08-1.21). The imputed sample showed that non-reverters were more likely to discontinue fieldwork or gardening (11.0% vs. 6.1%) than reverters during the follow-up period.
Specific lifestyle activities may play important roles in MCI reversion in older adults. The longitudinal data indicate that it is reasonable to recommend that individuals continue to engage in fieldwork or gardening to increase their chance of recovery from MCI.
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