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Background: Anorexia of aging (AA) is a condition in older adults that includes loss of appetite and reduced food intake. There is a lack of detailed analysis of the potential influence of educational initiatives in addressing AA. This study aimed to clarify the current state of knowledge and practice regarding AA and its relationship with the availability of continuing education opportunities among Japanese healthcare professionals involved in treating older patients., Methods: The Japan Geriatrics Society and the Japanese Association on Sarcopenia and Frailty, in collaboration with the Society on Sarcopenia, Cachexia, and Wasting Disorders, conducted an online questionnaire survey on the knowledge and practices in AA detection and management. Questions were asked in the areas of demographics, screening, definition/diagnosis, treatment, referral, and awareness, with those who 'participate' in continuing education and professional development programmes in nutrition for their patients were classified as the 'education group' and those who 'do not participate' were classified as the 'non-education group'. The results for each question were compared., Results: The analysis included 870 participants (physicians, 48%; registered dietitians, 16%; rehabilitation therapists, 14%; pharmacists, 12%; nurses, 6%; and other professionals, 5%). The education group (45%) was more likely than the non-education group (55%) to use the Mini-Nutritional Assessment Short Form (MNA-SF) to screen for AA (49% vs. 27%) and less likely not to use a validated tool (33% vs. 47%). More participants used evidence-based tools and materials for AA care (38% vs. 12%), and fewer used their clinical judgement (23% vs. 35%) or were unaware of the tools and materials (9% vs. 23%). The proportion using a team of professionals experienced in AA care were 47% and 24% of the education and non-education groups, respectively. By profession, few physicians used specific validated tools and resources for AA screening and treatment. More than half of the dietitians used the MNA-SF regardless of training opportunity availability. Regarding professional availability and team use, differences in educational opportunities were particularly large among physicians., Conclusions: Participation in continuing education programmes on nutrition is associated with responsiveness to AA screening and treatment and the availability of a team of professionals, which may influence the quality of AA treatment. Nutrition education may support the confidence of healthcare professionals working with older adults in AA with complex clinical signs and encourage them to conduct evidence-based practice., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Aim: The Questionnaire for Medical Checkup of Old-Old (QMCOO) has been used nationwide in Japan as part of the health checkup for latter-stage older adults since the financial year 2020. Although the QMCOO is useful in screening for frailty, its cutoff values for predicting adverse health outcomes have rarely been assessed. Therefore, this study aimed to calculate the cutoff values for predicting all-cause mortality and disability incidence and to evaluate their predictive validity., Methods: This study included 3837 health checkup recipients aged ≥75 years residing in Higashiura Town, Aichi Prefecture, Japan. The health checkup was conducted from June 1, 2020, to January 31, 2021. Mortality and disability incidence were analyzed separately. For the latter, participants with a disability history were excluded, leaving 3040 available for analysis., Results: During the follow-up of 11 191 and 8550 person-years, 276 died and 438 developed a disability, respectively. The areas under the receiver operating characteristic curve (95% confidence intervals) for all-cause mortality and disability incidence were 0.68 (0.65-0.71) and 0.66 (0.63-0.68), respectively, with QMCOO cutoff values at 3/4 and 2/3 points. Cox proportional hazard models adjusted for age, sex, body mass index, self-reported diseases, and frequency of alcohol consumption demonstrated the predictive validity of those cutoff values., Conclusions: The optimal cutoff value of the QMCOO for predicting all-cause mortality was 3/4, while the optimal cutoff value for predicting disability incidence was 2/3 among an older Japanese population. Geriatr Gerontol Int 2024; ••: ••-••., (© 2024 Japan Geriatrics Society.)

Skeletal muscle index measurement via dual-energy X-ray absorptiometry or bioelectrical impedance analysis is used to evaluate muscle mass when diagnosing sarcopenia. However, inherent challenges exist with these methods. We previously focused on muscle mass evaluation in the quadriceps femoris by using computed tomography (CT). In this observational study, we utilized a new ultrasound device with a wide field of view that can obtain CT-like images and investigated its usefulness. Reproducibility was investigated by calculating the intra- and inter-examiner intraclass correlation coefficient (ICC) by using three examiners and performing five measurements in 12 participants. In 123 participants (48 men, 75 women, mean age 78.2 ± 8.1 years), we investigated the correlation between the quadriceps cross-sectional area measured with supine ultrasound and CT images as well as between supine and sitting ultrasound images. Unadjusted, age-adjusted, and age-sex-adjusted correlations were calculated. Reproducibility was excellent (intra-examiner ICC[1,1]: 0.978, 0.987, and 0.994; inter-examiner ICC[2,1]: 0.993). The unadjusted, age-adjusted, and age-sex-adjusted correlations between the quadriceps cross-sectional area measured using supine ultrasound and CT were 0.949, 0.940, and 0.894, respectively. For sitting ultrasound, the corresponding values were 0.958, 0.953, and 0.912, respectively. Correlations between the supine and sitting ultrasound measurements were also good, with corresponding values of 0.952, 0.945, and 0.904, respectively. The tested ultrasound device showed excellent measurement reproducibility and had good correlations with CT images. Further studies with an increased numbers of clinical cases and additional evaluations should allow the device to become a screening tool for diagnosing sarcopenia., Competing Interests: This study was conducted based on the collaborative research contract between National Center for Geriatrics and Gerontology and Furuno Electric Co., Ltd. but this does not alter our adherence to PLOS ONE policies on sharing data and materials, as detailed online in our guide for authors http://journals.plos.org/plosone/s/competinginterests, if there are restrictions on sharing of data and/or materials., (Copyright: © 2024 Matsui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: This study investigated the relationship between food group and the changes in sarcopenia parameters in 1 year among older outpatients., Methods: A prospective cohort study conducted between July 2017 and April 2021 included patients aged ≥ 65 years attending a frailty clinic. Food group consumption adjusted for energy and body weight was conducted using a self-administered dietary history questionnaire. Ordinal logistic regression analysis was used to examine the association between tertiles of adjusted food group consumption and outcomes, including a handgrip strength decline, prolonged five-time chair stand test (5CST), decreased skeletal muscle mass index (SMI), and decreased gait speed in 1 year. Covariates included age, sex, height, energy intake, number of comorbidities, and the Baecke activity score., Results: In the analysis of 165 participants (mean age 77.6 ± 6.1 years, 107 women), individuals with higher consumption of sugar and sweeteners had a significantly increased risk for handgrip strength decline (OR 2.46, 95% CI 1.15-5.23, P = 0.020) and prolonged 5CST (OR 3.14, 95% CI 1.38-7.13, P = 0.006). Higher consumption of beverages increased the risk of handgrip strength decline (OR 2.30, 95% CI 1.11-4.76, P = 0.025). Conversely, higher legume consumption decreased the risk of SMI reduction (OR 0.35, 95%CI 0.16-0.76, P = 0.008), higher fruit consumption reduced the risk of prolonged 5CST time (OR 0.29, 95% CI 0.13-0.67, P = 0.004), and higher green yellow vegetables consumption decreased the risk of reduced gait speed (OR 0.38, 95% CI 0.17-0.84, P = 0.017)., Conclusion: Sugar, sweeteners, and beverages are associated with worsened sarcopenia parameters, whereas consumption of legumes, vegetables, and fruits is associated with a lower risk., (© 2024. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Objectives: The purpose of this study was to determine the associations of vision impairment, hearing impairment, and comorbid vision and hearing impairment [ie, dual sensory impairment (DSI)] on admission to hospital with falls within 3 months of discharge in older patients., Design: This prospective multicenter study included patients admitted to and discharged from geriatric wards at 3 university hospitals and 1 national medical center in Japan between October 2019 and July 2023., Setting and Participants: Of 1848 individuals enrolled during the study period, 1141 were excluded, leaving 707 for inclusion in the analysis., Methods: Participants' background factors were compared in terms of whether they had a fall during the 3 months postdischarge. Logistic regression analysis was then performed using the presence or absence of falls after discharge as the objective variable. Three models were created using vision impairment, hearing impairment, and DSI as covariates. Other covariates included physical function, cognitive function, and depression. In addition, logistic regression analysis was performed with falls during hospitalization as the objective variable., Results: DSI was significantly more common in the falls group (P = .004). Logistic regression analysis showed that the risk of falls after discharge was higher in patients with DSI (odds ratio 3.432, P = .006) than in those with vision or hearing impairment alone. When adjusted for physical function, cognitive function, depression, and discharge location, DSI was significantly associated with an increased risk of falls after discharge (odds ratio 3.107, P = .021). The association between DSI and falls during hospitalization did not reach statistical significance, but a trend was observed., Conclusions and Implications: This study is the first to show an association between DSI and falls after discharge. Simple interventions for patients with DSI may be effective in preventing falls, and we suggest that they be actively implemented early during hospitalization., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aims to evaluate the utility of body mass index (BMI)-adjusted calf circumference (CC) in estimating skeletal muscle mass and diagnosing sarcopenia, as well as its association with falls, a common adverse event in sarcopenia., Methods: This study used cross-sectional and longitudinal designs. The CC cut-off values and the diagnosis of sarcopenia were based on valid diagnostic criteria. BMI-adjusted CC was based on previous studies, with muscle mass measured by dual-energy X-ray absorptiometry. To evaluate the diagnostic performance of BMI-adjusted CC for low muscle mass and sarcopenia, receiver operating characteristic curves were generated, and the area under the curve (AUC) values were compared using DeLong's test. Over a 1 year follow-up period, factors associated with falls were examined using logistic regression analysis., Results: In the study of 901 older adults (77.6 ± 6.1 years, 63.6% women), 38.1% of men and 42.1% of women had a BMI outside the 18.5-24.9 kg/m 2 range. BMI-adjusted CC significantly lowered the AUC values for diagnosing low skeletal muscle mass and sarcopenia in both sexes (P < 0.001). Longitudinal univariate logistic regression analysis in women revealed that unadjusted CC was not significantly associated with fall risk, whereas BMI-adjusted CC significantly reduced fall risk at higher values. However, this association was no longer present in the multivariate analysis., Conclusion: The utility of BMI-adjusted CC in assessing skeletal muscle mass was not confirmed. The potential value of BMI-adjusted CC has been suggested regarding falls. Further research is warranted to better elucidate these findings., (© 2024. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Aims/introduction: The clinical significance of age-related biomarkers in patients with diabetes has not been fully elucidated. In this study, we aimed to establish models to predict the progression of aging in patients with diabetes using biomarkers., Materials and Methods: This single-center, retrospective cohort study included 115 Japanese patients with diabetes aged ≥60 years. Age-related adverse health outcomes were defined as emergency hospitalization, any increase in the level of nursing care certification, admission to a nursing home or death. The associations of age-related biomarker levels (adiponectin, growth differentiation factor 15 [GDF15], C-X-C motif chemokine ligand 9 and apelin) and clinical indicators with age-related adverse health outcomes were evaluated. Factors that predominantly influenced the occurrence of age-related adverse health outcomes were explored using the Cox proportional hazards model., Results: The mean age of the 115 participants was 73 years, 50.6% were men, the mean body mass index and hemoglobin A1c level were 25.3 kg/m 2 and 9.79%, respectively. There were 26 age-related adverse health outcomes during the study period (median 1.93, range 0-4.65 years). In a model combining clinical indicators and biomarkers, including the Barthel Index, GDF15 and adiponectin, the occurrence of age-related adverse health outcomes was found to be significantly associated with GDF15 and Barthel Index. The group with both GDF15 and adiponectin levels higher than the median proved to be significantly higher than the group with both lower., Conclusions: The measurement of GDF15 and adiponectin levels and the Barthel Index might be useful for predicting age-related adverse health outcomes in patients with diabetes., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Purpose: This study aimed to investigate how intrinsic capacity (IC) deficit is associated with oral functional decline., Methods: This cross-sectional study enrolled older adults at a research hospital frailty clinic between July 2021 and May 2023. IC evaluation included the locomotion, cognition, vitality, psychology, and sensory domains. Criteria for deficits were established within each domain, and the number of IC deficit domains was calculated for each patient. Oral function assessment included oral hygiene, oral dryness, occlusal force, tongue-lip motor function, tongue pressure, masticatory function, and swallowing function. Patients who met three or more criteria were classified into the oral hypofunction (OHF) group. Univariate and multivariate logistic regression analyses were performed to investigate the relationship between IC deficit and OHF., Results: Of 222 included patients (mean age 78.3 ± 6.3 years; 39.6% men), 105 (47.3%) met the criteria for OHF. This OHF group showed a significantly higher prevalence of locomotion, cognition, psychology, and sensory domain deficits than the normal oral function group. Multivariate analysis adjusted for age and sex revealed a significant association between IC deficits and OHF (odds ratio [OR], 1.33; 95% confidence interval [CI] 1.04-1.70). A significant association was also observed between the locomotion domain and OHF (OR, 2.06; 95% CI 1.13-3.76)., Conclusion: This study highlights the potential relationship between the number of IC domain deficits and oral functional decline, with the most significant domain being locomotion. Furthermore, it suggests a possible link between sensory and oral function., (© 2024. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Background: Japan, which has the world's longest life expectancy, has been reporting rejuvenation of physical function among its older adult population. However, evidence for the incidence of functional disability is limited. This study aimed to investigate the comparison in the incidence of functional disability., Design: We used data from the Japan Gerontological Evaluation Study., Setting and Participants: The participants were 2 nonoverlapping cohorts of 22,522 (2010-2013 cohort) and 26,284 (2016-2019 cohort) individuals aged 65 years and older from 5 municipalities who were followed for 3 years each., Methods: The incidence rates of functional disability during the 3-year follow-up period were compared between cohorts. To examine the incident differences between the cohorts, we adjusted for social participation and 9 additional factors that would be expected to improve with social participation using the Weibull survival models adjusting for municipalities as random effects. The analysis was stratified by age groups (65-74 years old and ≥75)., Results: The incidence rate of functional disability per 10,000 person-years decreased from 68.6 (2010-2013 cohort) to 51.4 (2016-2019 cohort) in the 65 to 74 years old group and 380.0 (2010-2013 cohort) to 282.6 (2016-2019 cohort) in the ≥75 group; the hazard ratios (95% CIs) were 0.75 (0.64-0.89) and 0.73 (0.67-0.80), respectively. However, these significant decreases disappeared with adjustments for social participation and additional factors., Conclusions and Implications: The incidence of functional disability decreased in a recent cohort, which may be explained by social participation and possibly related factors. Promoting social participation could contribute to a decreasing incidence of functional disability among older adults., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

[Purpose] Although many studies have shown that patients have difficulty in climbing or descending stairs after undergoing total knee replacement, no study so far has compared the difficulty of stair ascent and descent based on objective indicators. This study compared stair ascending and descending processes based on three indicators and clarified which was more difficult. [Participants and Methods] We defined 1) movement method, 2) the necessity for handrail use, and 3) speed as objective indicators. Seventy-eight patients who underwent total knee replacement participated in this study. Three months after the surgery, we examined 1) whether the patients could ascend or descend in a step-over-step or step-by-step manner, 2) whether the patients required handrail support, and measured 3) the time required to ascend and descend for four steps. [Results] The step-by-step movement and handrail requirement rates associated with stair descent were higher than the corresponding rates associated with stair ascent. In addition, the time required for stair descent was greater than that required for ascent. [Conclusion] We found that stair descent was more challenging than stair ascent in terms of all three objective indices: movement method, handrail use, and speed. The results indicate that rehabilitation after total knee replacement should focus more on stair descent than on stair ascent., Competing Interests: The authors declare no conflict of interest., (2024©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Background: At present, there are no consistent findings regarding the association between physical health loss and mental health in older adults. Some studies have shown that physical health loss is a risk factor for worsening of mental health. Other studies revealed that declining physical health does not worsen mental health. This study aimed to clarify whether the relationship between physical health loss and emotional distress varies with age in older inpatients post receiving acute care., Methods: Data for this study were collected from 590 hospitalized patients aged ≥ 65 years immediately after their transfer from an acute care ward to a community-based integrated care ward. Emotional distress, post-acute care physical function, and cognitive function were assessed using established questionnaires and observations, whereas preadmission physical function was assessed by the family members of the patients. After conducting a one-way analysis of variance (ANOVA) and correlation analysis by age group for the main variables, a hierarchical multiple regression analysis was conducted with emotional distress as the dependent variable, physical function as the independent variable, age as the moderator variable, and cognitive and preadmission physical function as control variables., Results: The mean GDS-15 score was found to be 6.7 ± 3.8. Emotional distress showed a significant negative correlation with physical function in younger age groups (65-79 and 80-84 years); however, no such association was found in older age groups (85-89, and ≥ 90 years). Age moderated the association between physical function and emotional distress. Poor physical function was associated with higher emotional distress in the younger patients; however, no such association was observed in the older patients., Conclusions: Age has a moderating effect on the relationship between physical health loss and increased emotional distress in older inpatients after acute care. It was suggested that even with the same degree of physical health loss, mental damage differed depending on age, with older patients experiencing less damage., (© 2024. The Author(s).)

Objectives: This study examined the diagnostic concordance and characteristics of the oral frailty five-item checklist (OF-5) and oral hypofunction (OHF)., Materials and Methods: In this extensive cross-sectional study, older adults were enrolled at a research hospital frailty clinic between July 2021 and July 2023. The diagnosis of OF-5 and OHF was conducted using the proposed assessment methods. The concordance rate of these criteria was determined by evaluating each patient and calculating the number of patients meeting each diagnosis's criteria. Patients who tested negative for the OF-5 and OHF criteria and those who met only one criterion were included in the OF-5 and OHF characteristic analysis., Results: A total of 248 patients were included in the analysis (mean age 77.6 ± 6.8 years; 36.7 % men). Among the patients, 114 (46.0 %) and 116 (46.8 %) met the OF-5 and OHF criteria, respectively. Furthermore, 78 (31.5 %) participants met both the OF-5 and OHF criteria, whereas 96 (38.7 %) did not meet either criterion. Moreover, 36 (14.5 %) and 38 (15.3 %) patients tested exclusively positive for OF-5 and OHF, respectively. The OF-5-positive and OHF-negative group showed an older age, lower Mini Nutritional Assessment Short Form score, and higher fall risk than the OF-5-negative and OHF-negative group. However, no significant differences were observed between the OF-5-negative and OHF-positive and OF-5-negative and OHF-negative groups., Conclusion: The concordance rate of OF-5 and OHF diagnoses was 70.2 %. OF-5 showed a potential association with nutritional status and fall risk. Further longitudinal analyses are warranted to explore our study results., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Zinc is crucial in the pathogenesis of hepatocellular carcinoma; however, no reports have examined its association with clinical parameters and zinc transporter 1 (ZNT1) expression intensity. This study aimed to assess the association between ZNT1 expression and prognosis in patients with hepatocellular carcinoma., Methods: This retrospective study included 65 patients who underwent surgical hepatocellular carcinoma resection at a single center between January 2011 and June 2015. ZNT1 expression on hepatocellular carcinoma cells from specimens was assessed using immunohistochemistry, and the relationship between its intensity and various clinical indexes was examined with univariate and multivariable analyses and the Mann-Whitney U, Kruskal-Wallis, Bonferroni, and log-rank tests., Results: ZNT1 expression on the hepatocellular carcinoma cell membrane was negative in 31 patients and positive in 34 patients, including nine patients showing strongly positive expression. Patients with and without ZNT1 expression had similar blood zinc concentrations, α-fetoprotein levels, protein induced by vitamin K absence-antagonist-II levels, gross classification, maximal tumor diameters, and background liver disease. The blood zinc concentrations were significantly lower in patients with strongly positive ZNT1 expression (57.0 ± 22.1 μg/dL) than in those with positive ZNT1 expression (71.1 ± 14.2 μg/dL; P = 0.015) or those with no ZNT1 expression (72.9 ± 14.1 μg/dL; P = 0.043). Overall survival was significantly shorter in ZNT1-expressing patients than in non-expressing patients (log-rank test, P = 0.024). Multivariable analysis using the Cox proportional hazards model identified maximal tumor diameter (hazard ratio, 1.018; 95% confidence interval, 1.002-1.034; P = 0.026) and ZNT1 expression status (hazard ratio, 2.082; 95% confidence interval, 1.196-3.621; P = 0.010) as prognostic contributing factors., Competing Interests: Declaration of Competing Interest All authors have declare: no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

The specification of the embryonic central nervous system (CNS) into future brain (forebrain, midbrain, or hindbrain) and spinal cord (SC) regions is a critical step of CNS development. A previous chicken embryo study indicated that anterior epiblast cells marked by Sox2 N2 enhancer activity are specified to the respective brain regions during the transition phase of the epiblast to the neural plate-forming neural primordium. The present study showed that the SC precursors positioned posterior to the hindbrain precursors in the anterior epiblast migrated posteriorly in contrast to the anterior migration of brain precursors. The anteroposterior specification of the CNS precursors occurs at an analogous time (∼E7.5) in mouse embryos, in which an anterior-to-posterior incremental gradient of Wnt signal strength was observed. To examine the possible Wnt signal contribution to the anteroposterior CNS primordium specification, we utilized mouse epiblast stem cell (EpiSC)-derived neurogenesis in culture. EpiSCs maintained in an activin- and FGF2-containing medium start neural development after the removal of activin, following a day in a transitory state. We placed activin-free EpiSCs in EGF- and FGF2-containing medium to arrest neural development and expand the cells into neural stem cells (NSCs). Simultaneously, a Wnt antagonist or agonist was added to the culture, with the anticipation that different levels of Wnt signals would act on the transitory cells to specify CNS regionality; then, the Wnt-treated cells were expanded as NSCs. Gene expression profiles of six NSC lines were analyzed using microarrays and single-cell RNA-seq. The NSC lines demonstrated anteroposterior regional specification in response to increasing Wnt signal input levels: forebrain-midbrain-, hindbrain-, cervical SC-, and thoracic SC-like lines. The regional coverage of these NSC lines had a range; for instance, the XN1 line expressed Otx2 and En2, indicating midbrain characteristics, but additionally expressed the SC-characteristic Hoxa5. The ranges in the anteroposterior specification of neural primordia may be narrowed as neural development proceeds. The thoracic SC is presumably the posterior limit of the contribution by anterior epiblast-derived neural progenitors, as the characteristics of more posterior SC regions were not displayed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nakamura, Watanabe, Boitet, Satake, Iida, Yoshihi, Ishii, Kato and Kondoh.)

Background: Although body mass index (BMI) and grip strength (GS) are both predictors of disability, their joint effect on predicting incident disability remains uncertain. We examined whether the effect of BMI on incident disability can be modulated by GS in community-dwelling older people in Japan., Methods: A total of 1486 community-dwellers in Japan (731 men and 755 women, aged 65-82 years) who participated in the 2nd to 7th waves of the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) project, were followed up to 20 years. Twelve subgroups were created according to the intersections of GS (sex-specific tertiles: low, intermediate, and high) and BMI (underweight 1, <18.5; underweight 2, 18.5-<21.5; normal, 21.5-<25.0; and overweight/obese, ≥25.0 kg/m 2 ). Incident disability was defined as requiring care need level 1 or higher, as per the long-term care insurance system in Japan. The hazard ratios (HR) and corresponding 95% confidence intervals (CI) of incident disability (the 'high GS-normal BMI' subgroup was used as the reference) were calculated using a multivariable-adjusted Cox proportional hazards model. The model was adjusted for baseline characteristics on sex, participation wave, smoking, depressive symptoms, total physical activity, disease history, education level, residential status, and energy intake., Results: Compared with that for participants in the 'high GS-normal BMI' group, the risk of incident disability was higher for participants in the 'low GS-normal BMI', 'low GS-overweight/obese', 'intermediate GS-underweight 1' and 'intermediate GS-overweight/obese' groups. The multivariable-adjusted HR (95% CI) were 1.72 (1.27-2.32, P value<0.001), 1.81 (1.27-2.58, P value = 0.001), 2.42 (1.35-4.32, P value = 0.003) and 1.53 (1.06-2.20, P value = 0.023), respectively. The results did not change substantially when participants with disability occurring within 1 and 2 years of follow-up were excluded, or when the competing events were death without incident disability or dementia., Conclusions: The joint effect of BMI and GS was more pronounced in those of normal weight or overweight/obese status and low GS, along with underweight or overweight/obese status and intermediate GS in predicting disability. The lack of observed joint effect for those underweight with low GS was likely due to insufficient sample size. GS consideration is necessary for weight management in older adults, and interventions for individuals who are underweight or overweight/obese with adequate GS need not be prioritized for disability prevention., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Introduction: Dysregulation of pro-inflammatory chemokines is considered a potential mechanism for the development of age-related medical conditions such as frailty. However, evidence linking circulating chemokines with frailty remains lacking., Materials and Methods: We performed a case-control study including 48 cases and 48 controls aged 65-90 years, using the National Center for Geriatrics and Gerontology outpatient registry data. Cases were outpatients with physical frailty and low habitual daily activity. Controls were robust outpatients who performed habitual daily activities. The Japanese version of the Cardiovascular Health Study criteria was used to diagnose physical frailty, and the modified Baecke questionnaire was used to evaluate habitual daily activities. Serum CXCL9 and CXCL10 levels were measured using enzyme-linked immunosorbent assay., Results: The median age (interquartile range) in cases and controls was 78 (73-83) and 76 (72-80) years, with the proportions of men were 47.9% and 43.8%, respectively. In the logistic regression model with adjustment for age, sex, and other confounding factors, the multivariable odds ratios (95% confidence intervals) for the highest versus lowest tertile of CXCL9 and CXCL10 levels were 7.90 (1.61-49.80) and 1.61 (0.42-6.30), respectively. However, we did not observe a linear association between CXCL9 levels and physical frailty components., Discussion/conclusion: Our preliminary data exhibit that circulating CXCL9 levels were positively associated with the odds of physical frailty. However, these findings lack evidence of a dose-response relationship between CXCL9 levels and physical frailty components. Further research with a larger sample size is required to confirm these findings., (© 2023 S. Karger AG, Basel.)

Matrix metalloproteinase-9 (MMP-9) is a secreted zinc-dependent endopeptidase that degrades the extracellular matrix and basement membrane of neurons, and then contributes to synaptic plasticity by remodeling the extracellular matrix. Inhibition of MMP-9 activity has therapeutic potential for neurodegenerative diseases such as fragile X syndrome. This paper reports the molecular design, synthesis, and in vitro studies of novel indole derivatives as inhibitors of proMMP-9 activation. High-throughput screening (HTS) of our internal compound library and subsequent merging of hit compounds 1 and 2 provided compound 4 as a bona-fide lead. X-ray structure-based design and subsequent lead optimization led to the discovery of compound 33, a highly potent and selective inhibitor of proMMP-9 activation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Although frailty is a geriatric syndrome that is associated with disability, hospitalization, and mortality, it can be reversible and preventable with the appropriate interventions. Additionally, as the current diagnostic criteria for frailty include only physical, psychological, cognitive, and social measurements, there is a need for promising blood-based molecular biomarkers to aid in the diagnosis of frailty., Methods: To identify candidate blood-based biomarkers that can enhance current diagnosis of frailty, we conducted a comprehensive analysis of clinical data, messenger RNA-sequencing (RNA-seq), and aging-related factors using a total of 104 older adults aged 65-90 years (61 frail subjects and 43 robust subjects) in a cross-sectional case-control study., Results: We identified two candidate biomarkers of frailty from the clinical data analysis, nine from the RNA-seq analysis, and six from the aging-related factors analysis. By using combinations of the candidate biomarkers and clinical information, we constructed risk prediction models. The best models used combinations that included skeletal muscle mass index measured by dual-energy X-ray absorptiometry (adjusted p = 0.026), GDF15 (adjusted p = 1.46E-03), adiponectin (adjusted p = 0.012), CXCL9 (adjusted p = 0.011), or apelin (adjusted p = 0.020) as the biomarker. These models achieved a high area under the curve of 0.95 in an independent validation cohort (95% confidence interval: 0.79-0.97). Our risk prediction models showed significantly higher areas under the curve than did models constructed using only basic clinical information (Welch's t test p &lt; 0.001)., Conclusion: All five biomarkers showed statistically significant correlations with components of the frailty diagnostic criteria. We discovered several potential biomarkers for the diagnosis of frailty. Further refinement may lead to their future clinical use., (© 2024 S. Karger AG, Basel.)

Sarcopenia is a geriatric disease associated with increased mortality and disability. Early diagnosis and intervention are required to prevent it. This study investigated biomarkers for sarcopenia by using a combination of comprehensive clinical data and messenger RNA-sequencing (RNA-seq) analysis obtained from peripheral blood mononuclear cells. We enrolled a total of 114 older adults aged 66-94 years (52 sarcopenia diagnosed according to the Asian Working Group for Sarcopenia 2019 consensus and 62 normal older people). We used clinical data which were not included diagnosis criteria of sarcopenia, and stride length showed significance by logistic regression analysis (Bonferroni corrected p = .012, odds ratio = 0.14, 95% confidence interval [CI]: 0.05-0.40). RNA-seq analysis detected 6 differential expressed genes (FAR1, GNL2, HERC5, MRPL47, NUBP2, and S100A11). We also performed gene-set enrichment analysis and detected 2 functional modules (ie, hub genes, MYH9, and FLNA). By using any combination of the 9 candidates and basic information (age and sex), risk-prediction models were constructed. The best model by using a combination of stride length, HERC5, S100A11, and FLNA, achieved a high area under the curve (AUC) of 0.91 in a validation cohort (95% CI: 0.78-0.95). The quantitative PCR results of the 3 genes were consistent with the trend observed in the RNA-seq results. When BMI was added, the model achieved a high AUC of 0.95 (95% CI: 0.84-0.99). We have discovered potential biomarkers for the diagnosis of sarcopenia. Further refinement may lead to their future practical use in clinical use., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Sarcopenic dysphagia (SD) is an emerging concern in geriatric medicine. This study aimed to identify the prevalence, progression, and distinct attributes of SD in patients in the Department of Geriatric Medicine. Older adult patients admitted between 2021 and 2022 were enrolled. The department conducts a comprehensive geriatric assessment (CGA) combined with a multidisciplinary team-based intervention, setting the standard for medical care. We diligently assessed the occurrence and development of dysphagia at both the admission and discharge phases. Of the 180 patients analyzed (38.9% male, mean age 86.0 ± 6.6 years), 22.8% were diagnosed with SD at admission, thrice the rate of other dysphagia variants. Only one patient had new-onset dysphagia during hospitalization, attributed to SD. Patients with SD showed a better recovery rate (18.9%) than those with other dysphagia types. Patients with diminished swallowing capacity had compromised nutritional profiles, diminished energy and protein consumption, and extended fasting durations. Although sarcopenia is a prevalent inducer of dysphagia in older adults, an integrated approach in geriatric medicine involving rehabilitation, nutrition, and dentistry is pivotal. Strategies rooted in CGA promise potential for addressing dysphagia.

To determine whether the mechanical properties of joint soft tissues such as cartilage can be calculated from quantitative magnetic resonance imaging (MRI) data, we investigated whether the mechanical properties of articular cartilage and meniscus scheduled to be resected during arthroplasty are correlated with the T2 relaxation time on quantitative MRI at the same location. Six patients who had undergone knee arthroplasty and seven who had undergone hip arthroplasty were examined. For the knee joint, the articular cartilage and lateral meniscus of the distal lateral condyle of the femur and proximal lateral tibia were examined, while for the hip joint, the articular cartilage above the femoral head was studied. We investigated the relationship between T2 relaxation time by quantitative MRI and stiffness using a hand-made compression tester at 235 locations. The patient-individualized template technique was used to align the two measurement sites. The results showed a negative correlation (from -0.30 to -0.35) in the less severely damaged articular cartilage and meniscus. This indicates that tissue mechanical properties can be calculated from T2 relaxation time, suggesting that quantitative MRI is useful in determining when to start loading after interventional surgery on cartilage tissue and in managing the health of elderly patients.

Cumulenes have attracted considerable attention due to their unique structural and electronic properties. Despite their high potential for constructing condensed π-conjugated molecules, the synthetic utility of longer cumulenes remains to be established owing to their inherently high reactivity. Conjugated bisbutatrienes having two cumulene moieties linked by a spacer as a mimic of a longer cumulene were evaluated. Here, the synthesis and characterization of hexafluorocyclopentane-bridged bisbutatrienes are described. These bisbutatrienes underwent various cyclizations, to construct the unique π-extended frameworks inaccessible by other methodologies. The bisbutatrienes were converted into fulvenes, pentalene, germacycle, and benzocyclobutene under various conditions. Furthermore, a cyclooctatetraene derivative was synthesized by a one-step dimerization of the bisbutatriene., (© 2023 Wiley-VCH GmbH.)

Aim: Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the standard surgical treatment modality for familial adenomatous polyposis (FAP). It is challenging to perform proctectomy and preserve anal sphincter function. In this video, precise mucosectomy of the anal canal via transanal minimally invasive surgery (MAC-TAMIS) is reported., Methods: An asymptomatic 35-year-old man was found to have a positive faecal occult blood test in routine screening examination and was diagnosed with FAP on colonoscopic examination. The patient was scheduled for total proctocolectomy with IPAA using the TAMIS approach combined with transanal total mesorectal excision. MAC-TAMIS was performed to preserve the internal anal sphincter during laparoscopy., Results: The total duration of surgery was 543 min, blood loss was minimal, and the postoperative course was uneventful. The postoperative hospital stay was 12 days. The pathological findings demonstrated no evidence of malignancy. Gastrographic imaging from the ileostomy showed sufficient size of the J pouch and good tonus of the anus at 6 months after surgery. The Wexner scores at 1, 3 and 6 months after ileostomy closure were 5, 3 and 0, respectively., Conclusion: The MAC-TAMIS technique is safe and feasible during total proctocolectomy with IPAA in patients with FAP. This technique allows us to precisely preserve the internal anal sphincter using a laparoscopic approach., (© 2023 The Association of Coloproctology of Great Britain and Ireland.)

Background: Microbiota have been reported to influence the development of various gastrointestinal neoplasms through the mechanism of sustained inflammation; however, few data are available regarding their influence on intraductal papillary mucinous neoplasms. The aim of this study was to assess the association between specific microbiota and the clinicopathologic characteristics of intraductal papillary mucinous neoplasms of the pancreas., Methods: DNA was extracted from formalin-fixed, paraffin-embedded samples of 30 patients who underwent pancreatectomy for intraductal papillary mucinous neoplasm, and polymerase chain reaction was used to create sequence libraries using the primer set for the V3 and V4 region of 16S recombinant DNA. Filtered sequence reads were then processed into operational taxonomic units with a 97% identity threshold and the relative abundance of bacteria compared between the 2 groups using operational taxonomic units., Results: There was a trend toward fewer Firmicutes and more Proteobacteria and Fusobacteria in the relative abundance of main duct operational taxonomic units than in branch duct operational taxonomic units. The relative abundances of Bacteroidetes (P < .01) and Fusobacteria (P = .04) were significantly higher in invasive intraductal papillary mucinous neoplasms than in noninvasive intraductal papillary mucinous neoplasms. The relative abundance of the intestinal type was significantly lower in Firmicutes than the relative abundance of the nonintestinal type (P = .04). Notably, main duct operational taxonomic units with the intestinal subtype were affected by increased proportions of Proteobacteria and Fusobacteria, and Fusobacteria were abundant in the intestinal type of invasive main duct operational taxonomic units., Conclusion: Intratumoral microbiota may be involved in the progression of operational taxonomic units., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Osteosarcopenia is a new definitional approach that can increase the risk of falls and fractures in elderly compared with that of osteoporosis and sarcopenia alone. However, biomarkers for osteosarcopenia have not been well identified. Thus, we aimed to explore the biomarkers of osteosarcopenia, including bone, muscle, and geriatric markers. Outpatients attending a frailty clinic were enrolled in the study. Osteosarcopenia was defined as the coexistence of osteoporosis and sarcopenia. Osteoporosis was defined according to the criteria of the Japan Osteoporosis Society. Sarcopenia was defined according to the Asian Working Group for Sarcopenia consensus (2019). We selected 35 blood/serum pathological parameters, including bone, inflammation, nutritional, and aging markers for the study. Logistic regression analysis for osteosarcopenia was performed to explore the biomarkers of osteosarcopenia. Of the total 600 patients with a mean age of 76.6 years, 595 were enrolled in the registry during the study period. Logistic regression analysis for osteosarcopenia showed that elevated thyroid-stimulating hormone (TSH) (odds ratio [OR]:1.375; 95 % confidence interval [CI]: 1.092-1.731), bone-specific alkaline phosphatase (BAP) (OR: 1.059; 95 % CI: 1.002-1.120), and estimated glomerular filtration rate (eGFR) (OR: 1.029; 95 % CI: 1.007-1.053) increased the likelihood of osteosarcopenia. On the other hand, elevated 25-hydroxyvitamin D (25OHD) (OR: 0.905; 95 % CI: 0.841-0.974), blood urea nitrogen (BUN) (OR: 0.895; 95 % CI: 0.829-0.966) and K (OR: 0.241; 95 % CI: 0.081-0.717) decreased the likelihood of osteosarcopenia. It is worthwhile to examine these biomarkers for older adult outpatients attending a frailty clinic for screening osteosarcopenia. Further studies are needed to investigate the effects of other markers of bone metabolism., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Previous studies suggest that lower serum levels of dehydroepiandrosterone sulfate (DHEA-S) are associated with physical frailty. Associations with subtypes of physical frailty have not been studied. This study aimed to investigate associations between serum DHEA-S levels and physical frailty and its subtypes in older Japanese community-dwellers using panel data., Methods: This study was conducted within the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA). Repeated measurement data were collected from 1,886 older community-dwellers (60-91 years). Frailty was identified according to modified Cardiovascular Health Study criteria (weight loss, weakness, slowness, exhaustion, low physical activity) and was classified into following subtypes: mobility (weakness/slowness), non-mobility (weight loss/exhaustion), and low physical activity. Associations with serum DHEA-S (sex-specific tertiles [T1-T3]) were estimated by random-effects logistic regression models adjusting for age, sex, education, disease history (stroke, hypertension, heart disease, diabetes), smoking status, depressive symptoms, and survey wave., Results: We found an average prevalence of 6.0% for frailty (mobility subtype, 7.0%; non-mobility subtype, 34.8%; low physical activity subtype, 9.4%) across survey waves. Mean (SD) sex-specific DHEA-S levels (μg/dL) at T1, T2, and T3 were 46.8 (20.8), 88.7 (28.4), and 158.0 (58.9), respectively. Compared with T1, the adjusted ORs (95% CIs) for frailty were 0.69 (0.44, 1.08) for T2 and 0.50 (0.30, 0.83) for T3 (P trend = 0.007). The corresponding values for mobility subtype were 0.80 (0.51, 1.24) for T2 and 0.55 (0.33, 0.90) for T3., Conclusion: Higher serum DHEA-S levels were associated with lower risk of frailty, especially mobility-subtype frailty, in older community-dwellers., Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2022. Published by Elsevier B.V.)

Objectives: The FRAIL-NH scale was developed to identify frailty status in nursing home residents. The purpose of this study was to examine the utility of the FRAIL-NH scale for predicting nursing home admission among patients in post-acute care settings. Design/ Setting/ Participants: This single-center, prospective, observational cohort study included participants aged 65 years or older who were admitted to a community-based integrated care ward (CICW) between July 2015 and November 2020., Measurements: Using the CICW database, we retrospectively classified participants as robust, prefrail, or frail based on the FRAIL-NH scale the score by identifying variables from our database that were most representative of each component. The following data were collected: examination findings, CICW admission and discharge information, length of CICW stay, and nursing home admission. The participants were divided into two groups based on whether or not they were admitted to a nursing home after CICW discharge. The hazard ratios (HRs) and 95% confidence intervals (CIs) for nursing home admission were calculated according to the FRAIL-NH categories using the Cox proportional hazards models with reference to the robust group. In the multivariate adjusted model, we adjusted for age, sex, nutritional status, cognitive function, living status, and economic status., Results: Data of 550 older adults were analyzed, of which 118 were admitted and 432 were not admitted to a nursing home. The frail group had a higher risk of nursing home admission (HR, 2.22; 95% CI 1.32-3.76) than the robust group., Conclusions: This study showed that the FRAIL-NH scale was beneficial for predicting nursing home admission among older adults in the post-acute care setting. Thus, assessment using the FRAIL-NH scale may help to consider preparation and support for life after discharge., Competing Interests: The authors declare no conflict of interest.

Introduction: This study aimed to assess the clinical significance of eligibility criteria determined by phase 3 clinical trials in the clinical practice of patients with advanced gastric cancer who underwent chemotherapy., Methods: Patients with stage IV gastric cancer who received chemotherapy between February 2002 and December 2021 were retrospectively enrolled and divided into two groups (the eligible vs. ineligible group) based on eligibility criteria determined by the SPIRITS (S-1 vs. S-1 plus cisplatin) trial., Results: Among the 207 patients, 103 (49.8%) and 104 (50.2%) patients were classified into eligible and ineligible groups, respectively. Eligibility criteria were significantly correlated with age, the first-line regimen of chemotherapy, the presence or absence of conversion surgery, and tumor response to the first-line chemotherapy (all p < 0.01). The eligible group had a significantly higher induction of post-progression chemotherapy after first- and second-line chemotherapy than did the ineligible group (all p < 0.01). The ineligible group had significantly poorer prognoses than the eligible group (p < 0.0001). Multivariate analysis showed that peritoneal dissemination, tumor response, conversion surgery, and eligibility criteria were independent prognostic factors (all p < 0.05)., Conclusion: Eligibility criteria determined by the SPIRITS trial may have clinical utility for predicting tumor response, the induction of conversion surgery, and prognosis in patients with advanced gastric cancer who underwent chemotherapy., (© 2022 S. Karger AG, Basel.)

Background: Diet-induced inflammation may be associated with sarcopenia; however, few reports have examined this relationship., Aim: To examine the association between the dietary inflammatory index (DII) and sarcopenia in older adults who visited a frailty clinic in Japan., Methods: This cross-sectional study used outpatient data from the Frailty Registry Study. The DII is an index of diet-induced inflammation, and a dietary assessment was performed using a brief self-administered diet history questionnaire to calculate the DII score. We classified DII scores by quartiles (Q1-Q4), and sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia 2019 consensus. Logistic regression analyses for sarcopenia were performed. Age, sex, comorbidities, and physical activity were entered as confounding factors (Model 1) and Models 2, 3, and 4 with BMI, protein intake, and energy intake added to Model 1., Results: We included 304 patients in the analysis (mean age, 77.6 ± 6.3 years; female, 67.4%). The prevalence of sarcopenia was 14.5%. Logistic regression analyses showed that DII scores were significantly associated with sarcopenia in Model 1 and 2 (Model 1, reference: Q1, Q4: OR 3.10, P = 0.020; Model 2, Q4: OR 3.40, P = 0,022) but not in Model 3 and 4., Discussion: Diet-induced inflammation is associated with a higher likelihood of sarcopenia; however, this association disappeared after confounding for protein and energy intake., Conclusions: The results demonstrated that dietary protein and energy parameters were the main drivers for muscle health in medical patients., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Aim: The original Kihon Checklist, validated to predict the incidence of functional disability, has been modified to capture both functional ability (can/cannot) and performing state (do/do not). However, the predictive validity of the modified Kihon Checklist remains unverified. Therefore, this study intends to verify the predictive validity of the modified Kihon Checklist and to clarify whether predictive discrimination differs between the classification method of functional ability and performing state., Methods: The participants comprised 67 398 older people who responded to the Japan Gerontological Evaluation Study (2016). They were followed for 3.1 years on average. Cox's proportional hazards model with incidence of functional disability as the endpoint was used to calculate the hazard ratio, adjusted for sex and age. The independent variables were judged by two classification methods, functional ability and performing state, using nine indicators based on the modified Kihon Checklist. Additionally, we examined whether the two classification methods produced different C-index estimates., Results: Incidence of functional disability occurred in 6232 participants (9.2%). The adjusted hazard ratio of those to whom the nine indicators applied was significantly higher than that of those to whom they did not. The range of the hazard ratio was 1.50-3.82 for both classification methods. The C-index was slightly higher when the classification was based on performing state than when it was based on on functional ability., Conclusions: Although predictive discrimination was slightly higher for the performing state than for functional ability, the predictive validity of the modified Kihon Checklist was confirmed for both. Geriatr Gerontol Int 2022; 22: 667-674., (© 2022 The Authors. Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Objectives: To evaluate the contribution of a preextubation chest X-ray (CXR) to identify the risk of extubation failure in mechanically ventilated patients., Design: Retrospective cohort study., Settings: ICUs in a tertiary center (the Medical Information Mart for Intensive Care IV database)., Patients: Patients greater than or equal to 18 years old who were mechanically ventilated and extubated after a spontaneous breathing trial., Interventions: None., Measurements and Main Results: Among 1,066 mechanically ventilated patients, 132 patients (12%) experienced extubation failure, defined as reintubation or death within 48 hours of extubation. To predict extubation failure, we developed the following models based on deep learning (EfficientNet) and machine learning (LightGBM) with the training data: 1) model using only the rapid-shallow breathing index (RSBI), 2) model using RSBI and CXR, 3) model using all candidate clinical predictors (i.e., patient demographics, vital signs, laboratory values, and ventilator settings) other than CXR, and 4) model using all candidate clinical predictors with CXR. We compared the predictive abilities between models with the test data to investigate the predictive contribution of CXR. The predictive ability of the model using CXR as well as RSBI was not significantly higher than that of the model using only RSBI (c-statistics, 0.56 vs 0.56; p = 0.95). The predictive ability of the model using clinical predictors with CXR was not significantly higher than that of the model using all clinical predictors other than CXR (c-statistics, 0.71 vs 0.70; p = 0.12). Based on SHapley Additive exPlanations values to interpret the model using all clinical predictors with CXR, CXR was less likely to contribute to the predictive ability than other predictors (e.g., duration of mechanical ventilation, inability to follow commands, and heart rate)., Conclusions: Adding CXR to a set of other clinical predictors in our prediction model did not significantly improve the predictive ability of extubation failure in mechanically ventilated patients., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Self-organized structure formation in magnetically confined plasmas is one of the most attractive subjects in modern experimental physics. Nonequilibrium media are known to often exhibit phenomena that cannot be predicted by superposition of linear theories. One representative example of such phenomena is the hydrogen isotope effect in fusion plasmas, where the larger the mass of the hydrogen isotope fuel is the better the plasma confinement becomes, contrary to what simple scaling models anticipate. In this article, threshold condition of a plasma structure formation is shown to have a strong hydrogen isotope effect. To investigate the underlying mechanism of this isotope effect, the electrostatic potential is directly measured by a heavy ion beam probe. It is elucidated that the core electrostatic potential transition occurs with less input power normalized by plasma density in plasmas with larger isotope mass across the structure formation. This observation is suggestive of the isotope effect in the radial electric field structure formation., (© 2022. The Author(s).)

Background: Osteosarcopenia is a newly described, aging-associated condition. Social frailty is an important condition whose prevalence may have risen by physical distancing during the coronavirus disease 2019 pandemic. However, the relationship between these two remains unclear., Aims: To examine the association between osteosarcopenia and social frailty., Methods: This cross-sectional study was conducted using data from outpatients visiting general geriatric hospital frailty clinics. Bone mineral density (BMD) and muscle mass were measured using dual X-ray absorptiometry. Osteoporosis was defined as a BMD of < 70% of the young adult mean, according to the Japan Osteoporosis Society. Sarcopenia was diagnosed as per the Asian Working Group for Sarcopenia 2019 recommendation. Osteosarcopenia was defined as the co-existence of osteoporosis and sarcopenia. We defined social frailty using a questionnaire comprising four items: general resources, social resources, social behavior, and basic social needs. Ordinal logistic regression analysis was performed with social frailty status and osteosarcopenia as the dependent and independent variables, respectively., Results: We included 495 patients (mean age = 76.5 ± 7.2 years) in the analysis; of these, 58.2% were robust and 17.2%, 13.5%, and 11.1% had osteoporosis alone, sarcopenia alone, and osteosarcopenia, respectively. Social frailty prevalence increased stepwise from 8.0% in robust patients to 11.8%, 17.9%, and 29.1% among those with osteoporosis alone, sarcopenia alone, and osteosarcopenia, respectively (P < 0.001). Logistic regression analysis revealed that only osteosarcopenia was significantly associated with social frailty (pooled odds ratio: 2.117; 95% confidence interval: 1.104-4.213)., Discussion: Comprehensive assessment of osteosarcopenia and social frailty is needed for disability prevention in older adults., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Increasing age is associated with frailty and a higher prevalence of overactive bladder (OAB). Given the rapidly increasing proportion of older adults in Japan, a better understanding of the relationship between frailty and OAB is needed to inform future healthcare planning. This study assessed the association between frailty and OAB in older adults in Japan and evaluated the impact on their health-related quality of life (HRQoL)., Methods: This was a cross-sectional re-contact study of respondents who previously completed the National Health and Wellness Survey 2018 in Japan. Participants were aged ≥65 years and Japanese speakers and readers. As part of a customized online survey, participants were screened for frailty using the Kihon Checklist (frail = scores ≥8 points) and OAB using the overactive bladder symptom score (OAB = total score ≥ 3 points and ≥ 2 points on question 3). The primary endpoint was the odds ratio of frailty in older adults with and without OAB assessed using a multivariable logistic regression model. Secondary endpoints were the prevalence rates of OAB and frailty. Exploratory endpoints assessed HRQoL using the Medical Outcomes Study 12-Item Short Form Survey Instrument version 2 (SF-12v2)., Results: Overall, 2953 participants were included: 150 (5.1%) were frail OAB, 416 (14.1%) non-frail OAB, 287 (9.7%) frail non-OAB, and 2100 (71.1%) non-frail non-OAB. There was a statistically significant correlation between frailty and OAB demonstrated by an adjusted odds ratio (95% CI) of 2.78 (2.18-3.54; p <  0.001). The prevalence (95% CI) of OAB was 34.3% (29.9-38.8) in frail and 16.5% (15.1-18.0) in non-frail older adults; the prevalence of frailty was 26.5% (22.9-30.1) and 12.0% (10.7-13.3) in older adults with and without OAB. HRQoL was assessed in 150 participants per group. The adjusted HRQoL analyses showed significantly lower scores in participants who were frail OAB vs. frail non-OAB for most of the SF-12v2 scores/sub-component scores., Conclusions: These data highlight the statistically significant positive correlation between frailty and OAB among older adults in Japan and may provide valuable information on the burden of OAB and frailty on older adults to healthcare professionals when considering future healthcare planning., (© 2022. The Author(s).)

The Frailty screening should be widely performed; however, simple and inexpensive biomarkers are missing. Biomarkers that can be routinely assessed in many patients are desirable. Recently, the hemoglobin-to-red cell distribution width ratio (Hb/RDW, HRR) has been suggested as a new prognostic marker and has been reported to be associated with inflammation, one of the factors contributing to frailty. Therefore, we aimed to address the role of HRR in frailty among 557 older outpatients (aged 65-96 years). Frailty was assessed using the Japanese version of the Cardiovascular Health Study criteria, and HRR was calculated from clinical records. Participants were classified into five groups based on a sex-stratified quintile of HRR (Q1-Q5). Of the participants, 20.3% were frail. Using multiple logistic regression models with the Q5 group as a reference, after adjusting for sex, age, body mass index, polypharmacy, pre-orthopedic surgery, and the use of iron medications, the multivariable-adjusted odds ratios (95% confidence intervals) of the Q4 to Q1 groups were 0.92 (0.58-1.47), 1.04 (0.67-1.61), 1.29 (0.84-1.96), and 1.85 (1.22-2.82), respectively, indicating that a lower HRR was significantly associated with frailty. The robustness of these results was also shown in the multiple imputation analysis. The results suggest that HRR measurement may be one of the indicators to identify frail older adults in routine practice., Competing Interests: The authors declare no conflicts of interest in the present study.

Background: The coronavirus disease (COVID-19) pandemic has resulted in reduced physical activity and social interaction. These restrictions may have affected the food intake habits of frail older people more than non-frail older people., Objectives: To investigate the association between frailty and change in dietary habit during the pandemic., Design: Cross-sectional mail survey., Setting: Community-based., Participants: The study questionnaire was mailed to 4,436 older residents of Higashiura, Aich Japan, who were aged ≥75 years and who did not need care as of April 1, 2020. Of these, 2,738 participants provided complete answers to the questionnaires (75-96 years old, 49.3% males)., Measurements: The participants' frailty status and changes in food consumption during social isolation were assessed. Frailty status was assessed using the five-item frailty screening index (i.e., weight loss, low physical function, low physical activity, cognition, and exhaustion). Any participant who reported an increase or a decrease in ≥1 of the 12 food categories was defined as having change in dietary habit. Using multivariate logistic regression analysis, the odds ratios (ORs) and 95% confidence intervals (CIs) of frailty for changes in diet were estimated by adjusting for age, sex, BMI, and living alone. In each of the 12 food categories, the proportion of participants with increased and decreased food intake was compared between the groups., Results: Among the participants, 470 (17.2%) were frail, and 1,097 (40.1%) experienced a change in dietary habit under social restriction. The adjusted OR (95% CI) of the frail group for a change in dietary habit was 2.01 (1.63-2.47, p<0.001). Participants with decreased consumption of meat, fish, seaweed and mushroom, and fruits and those with increased consumption of eggs, bread, and noodles tended to be frail., Conclusion: The nutritional intervention for frail older people should be strengthened during the pandemic., Competing Interests: All the authors declare no conflicts of interest in the present study.

Purpose: Osteosarcopenia and cognitive frailty are both risk factors for falls and fractures. The purpose of this study was to determine the association between osteosarcopenia and cognitive frailty., Materials and Methods: This was a cross-sectional secondary data analysis of the Frailty Registry Study with outpatients aged ≥65 years who visited a frailty clinic at a geriatric hospital. Osteoporosis was defined as a bone mineral density < 70% of the young adult mean. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia 2019 criteria. Cognitive frailty was defined as the coexistence of physical frailty and mild cognitive impairment. Physical frailty was evaluated according to Japanese Cardiovascular Health Study criteria, whereas mild cognitive impairment was defined as a Mini-Mental State Examination score ≥ 24 points and a score ≤ 25 points on the Japanese version of the Montreal Cognitive Assessment. We performed multivariable logistic regression analysis to investigate the association between osteosarcopenia and cognitive frailty., Results: The data of 432 patients were analysed. The prevalence of osteosarcopenia and cognitive frailty was 10.2% and 20.8%, respectively. Logistic regression analysis revealed that osteosarcopenia was independently associated with cognitive frailty with a higher odds ratio than osteoporosis or sarcopenia alone. Lost points in visuospatial abilities/executive functions and orientation were significantly associated with osteosarcopenia., Conclusions: Combination of osteoporosis and sarcopenia is more likely to be associated with physical and cognitive decline than osteoporosis and sarcopenia alone. The mechanism by which osteosarcopenia is associated with decreased visuospatial abilities/executive functions and orientation needs to be addressed., (Copyright © 2021. Published by Elsevier B.V.)

Competing Interests: The authors declare that they have no conflict of interest.

Background: Gait disturbance and musculoskeletal changes are evident in persons living with Alzheimer's disease (AD). Because complex gait control requires the integration of neural networks, cerebral small vessel disease (SVD), which is highly prevalent in persons with AD, might have an additional impact on gait disturbance. This study investigated whether white matter hyperintensities (WMH) are more predominantly associated with gait disturbance in persons with AD than in individuals with mild cognitive impairment (MCI) and normal cognition (NC) and further identified the regional impact of WMH on specific gait changes., Methods: This study included 396 subjects (aged 65 to 86 years, 63.9% female) diagnosed with AD (n = 187), MCI (n = 118), or NC (n = 91). WMH, lacunes, perivascular spaces, and cerebral microbleeds were assessed as markers of SVD. The volume of WMH was quantified in each brain lobe (frontal, temporal, occipital, and parietal) and sublobar regions in the basal ganglia and thalamus. Gait function was assessed using an electronic walkway. We investigated the association between regional WMH and gait disturbance in individuals with AD, MCI, and NC, adjusted for classical and musculoskeletal confounders., Results: Among markers of SVD, WMH were most associated with gait disturbance. In AD subjects, periventricular WMH in the frontal and parietal lobes were associated with slow gait speed (r s  = -0.21, P = 0.007 and r s  = -0.18, P = 0.019, respectively). These lesions were also associated with changes in stride time, double-leg support time, and walking angle (all r s  > 0.20, P < 0.01). Lesions in the basal ganglia and thalamus were associated with slow gait speed (r s  = -0.16, P = 0.034 and r s  = -0.18, P = 0.023, respectively) and greater gait speed variability (r s  = 0.16, P = 0.034 and r s  = 0.20, P = 0.010, respectively). MCI subjects showed only associations between sublobar lesions and shorter stride length (r s  = -0.24, P = 0.016) and increased walking angle (r s  = 0.32, P = 0.002). NC subjects did not show associations between WMH and gait parameters. MCI and NC subjects were more affected by muscle weakness than WMH for global gait function (r s  = 0.42, P < 0.001 and r s  = 0.23, P = 0.046, respectively)., Conclusions: Persons with AD showed a predominant association between WMH and gait disturbance compared with MCI and NC subjects, and regional WMH had a detrimental effect on specific gait changes., (© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

We assess the magnetic field configuration in modern fusion devices by comparing experiments with the same heating power, between a stellarator and a heliotron. The key role of turbulence is evident in the optimized stellarator, while neoclassical processes largely determine the transport in the heliotron device. Gyrokinetic simulations elucidate the underlying mechanisms promoting stronger ion scale turbulence in the stellarator. Similar plasma performances in these experiments suggests that neoclassical and turbulent transport should both be optimized in next step reactor designs.

Purpose: The Asian Working Group for Sarcopenia 2019 (AWGS 2019) proposed a simple assessment of sarcopenia called "possible sarcopenia" for the purpose of early detection and intervention of sarcopenia. The purpose of this study was to report the accuracy of possible sarcopenia against definitive sarcopenia and the characteristics of false-negative cases., Materials and Methods: This was a cross-sectional study using a research registry with outpatients aged ≥65 years who visited a frailty clinic at a geriatric hospital. The diagnosis of possible sarcopenia and sarcopenia was performed according to the AWGS 2019 criteria, using calf circumference (CC) for case-finding. The accuracy of the diagnosis of sarcopenia in participants with possible sarcopenia was evaluated by calculating sensitivity, specificity, and F-value., Results: Of the 349 patients (mean age, 78.0±6.0 years; 63% women) analyzed, 86 (24.6%) revealed possible sarcopenia. Possible sarcopenia predicted sarcopenia with a sensitivity of 0.893 and 0.921, specificity of 0.990 and 0.870, and F-values of 0.926 and 0.714 for men and women, respectively. When either the grip strength test or 5-time chair stand test result was examined, the sensitivity of possible sarcopenia to predict sarcopenia decreased, whereas the specificity remained at 0.990-1.000 in men and 0.890-0.940 in women. An extremely decreased CC was identified as a significant characteristic of patients with sarcopenia not detected in the simplified assessment., Conclusions: The diagnostic accuracy of possible sarcopenia for definitive sarcopenia is excellent. Sarcopenia should be actively examined in patients with extremely decreased CC., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Social frailty is associated with poor health outcomes; however, its effects on healthy aging indicators have not been adequately investigated. This study assessed the longitudinal association between social frailty and the intrinsic capacity of community-dwelling older adults., Methods: A total of 663 participants (56.7% women) aged ≥60 years from in Nagoya, Japan, were included in the study. The first measurement occurred in 2014, and annual follow-ups occurred until 2017. Social frailty was determined based on four items: financial difficulty, household status, social activity, and regular contact with others. A deficit score of 0 represented social robustness, 1 represented social prefrailty, and ≥ 2 represented social frailty. Intrinsic capacity was evaluated by the locomotion, cognition, psychological function, vitality, and sensory function domains. The longitudinal association was analyzed using generalized estimating equations., Results: The prevalence of social prefrailty and social frailty at baseline was 31.2 and 6.3%, respectively. The social prefrailty group (β = - 0.132, P < 0.001) and social frailty group (β = - 0.258, P < 0.001) were associated with a greater reduction in the composite intrinsic capacity scores than the social robustness group, especially in the cognition, psychological function, and vitality domains. Men with social prefrailty/social frailty demonstrated a greater decrease in the psychological function domain score (- 0.512 vs. - 0.278) than women. Additionally, the cognition domain score only decreased in men in the social prefrailty/social frailty group (β = - 0.122, P = 0.016)., Conclusions: Social frailty was associated with intrinsic capacity and its subdomains longitudinally. Men with social frailty were more vulnerable than women to a decline in their psychological function and cognition domains. Therefore, the advanced management of social frailty is necessary to facilitate healthy aging., (© 2021. The Author(s).)

Purpose: The WHO has proposed a novel model of healthy aging called intrinsic capacity (IC). However, the association between dietary patterns and IC is unclear. We aimed to investigate the prospective associations between dietary patterns and IC trajectories over a 3-year period in community-dwelling Japanese adults aged ≥ 60 years., Methods: A prospective cohort study which contained nutritional status, mental status, and physical function was used. A validated 34-item food frequency questionnaire was used to determine dietary intake and to derive five dietary patterns ("fruits and vegetables", "sugar and fat", "salt and pickles", "noodle and alcohol", and "protein-rich") using principal component analysis. The composite IC score was calculated as the mean of the locomotion Z-score, cognition Z-score, psychological Z-score, vitality Z-score, and sensory regression score. A generalized estimating equation was applied for longitudinal analysis., Results: A total of 666 enrollees were included in the analysis. The mean baseline IC was 0.07 ± 0.47. The "fruits and vegetables" dietary pattern was positively associated with composite IC score changes after adjusting for confounders (Q4 vs. Q1: mean difference [0.069], P = 0.019). Similarly, a positive correlation was observed for the "protein-rich" dietary pattern with the composite IC score changes (Q4 vs. Q1: mean difference [0.092], Q3 vs. Q1: mean difference [0.101], Q2 vs. Q1: mean difference [0.083]; all P < 0.01). However, adherence to the "sugar and fat" dietary pattern was negatively associated with composite IC score changes (Q4 vs. Q1: mean difference [- 0.072], P = 0.026). Furthermore, the percentage of animal protein to total protein intake showed a significant incremental trend in the "protein-rich" dietary pattern (P for trend < 0.001)., Conclusion: The "fruits and vegetables" and "protein-rich" (animal-based protein in particular) dietary patterns were positively associated with IC changes, whereas the "sugar and fat" dietary pattern was negatively associated with IC changes. Identification and promotion of healthy dietary patterns in older adults may inform future health policies and research., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Frailty prevention is a cornerstone for the extension of healthy life expectancy. It is a multi-dimensional construct that includes physical, mental, and social aspects. Frailty is reversible and can be attenuated by intervention; therefore, its early detection is important in primary and community care. The mainstream of disability prevention in Japan, which comprises the Japanese and local governments as well as healthcare workers, was a high-risk approach until 2014. Given the revision on Japan's long-term care insurance law, current ageing health policies have shifted to more population centric approach. Implements group activities called "Kayoi-no-ba" has been valued in Japan as disability prevention initiative. The Kihon Checklist - a 25-item questionnaire - has been broadly used by health experts and researchers to assess frailty in Japan. However, a new 15-item questionnaire has been newly developed to identify frailty and other health-related problems in older people of 75 years and above. This will enable providing the necessary support to frail individuals at any healthcare facility in local communities. The increase in frailty prevalence in older people has been concern during the COVID-19 pandemic. Home-based physical exercise programs are expected to be effective for frailty prevention. Utilization of information and communication technologies, social network services, and video calls has attracted attention for being effective tools to facilitate communication for older people during the pandemic. Further, life course approaches are needed to clarify the midlife risk of frailty development in later life., Competing Interests: The authors have no conflicts of interest to disclose., (2021, National Center for Global Health and Medicine.)

Introduction: We report a case of COVID-19 with Legionella co-infection that was treated successfully., Case Report: A 73-year-old man presented to the hospital with symptoms of fatigue that continued for the next 5 days. The patient was receiving docetaxel and prednisolone chemotherapy for prostate cancer. Laboratory findings on admission showed positive urine Legionella antigen test and SARS-CoV-2 test. He was administered antiviral and antibacterial agents, and a corticosteroid. Pneumonia exacerbated on day 2 of hospitalization. The patient underwent tracheal intubation and began receiving multidisciplinary care. On day 8 of hospitalization, his oxygenation improved, and the patient was extubated. He discharged on day 27 of hospitalization., Conclusions: The patient had a favorable outcome with early diagnosis and early treatment of both diseases. Patients with severe COVID-19 disease need to be evaluated for co-infection. Further, early diagnosis and early treatment of the microbial bacteria causing the co-infection are important., (© 2021. The Author(s).)

Background: Despite the progress in endoscopic hemostasis and pharmacological treatment, the mortality rate of peptic ulcer bleeding remains at 5-10%. Rebleeding after peptic ulcer bleeding is believed to be a risk factor for mortality. This study aimed to evaluate whether renal dysfunction is a predictor of rebleeding after endoscopic hemostasis in patients with peptic ulcer bleeding., Methods: In this retrospective study, consecutive patients with peptic ulcer bleeding who underwent endoscopic hemostasis at our Hospital from January 2010 to December 2018 were enrolled. The relationship between rebleeding within 30 days after endoscopic hemostasis and the patients' admission and endoscopic characteristics were analyzed using univariate and multivariate regression models., Results: Out of 274 patients with peptic ulcer bleeding, 17 (6.2%) patients experienced rebleeding. In the analysis of the patients' admission characteristics, estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 was an independent risk factor for rebleeding (odds ratio 4.77, 95% confidence interval 1.168-18.211, p = 0.03). Patients with eGFR < 15 mL/min/1.73 m2 with or without hemodialysis had the highest rebleeding rate at 36.8%. With respect to endoscopic characteristics, the rate of rebleeding was associated with combination therapy (p < 0.0001) and active bleeding (p = 0.03)., Conclusion: Renal dysfunction might be an independent risk factor for rebleeding after endoscopic hemostasis in patients with peptic ulcer bleeding.

A 49-year-old man was found to have an elevated lesion on esophagogastroduodenoscopy (EGD) for gastric cancer screening. This lesion had been noted in EGD 13 years earlier, but the patient had not received EGD since then. Endoscopy showed a relatively soft subepithelial lesion (SEL) in the gastric antrum. In addition, endoscopic ultrasonography (EUS) showed a 20-mm-sized, slightly non-uniform hypoechoic mass in the submucosa. Since the diagnosis could not be confirmed by mucosal biopsy, EUS-guided fine-needle aspiration (EUS-FNA) was performed. Hematoxylin-eosin staining of EUS-FNA samples revealed deposition of acidophilic unstructured materials. The structure was positive on Congo red staining, and green polarized light was also observed under a polarizing microscope. Moreover, it was resistant to potassium permanganate reaction, negative for serum amyloid A protein, positive for anti-λ chain antibody, and negative for anti-κ chain, anti-amyloid A, anti-transthyretin, and anti-β2-microglobulin antibodies. Therefore, the lesion was diagnosed as AL-λ-type amyloidosis. No systemic amyloidosis findings were found; thus, the patient was finally diagnosed with localized gastric AL amyloidosis. If an SEL is seen without disease-specific endoscopic findings, amyloidosis should be included in the differential diagnosis, and EUS-FNA can contribute to obtaining tissue samples in such cases., (© 2021. Japanese Society of Gastroenterology.)

Background: SATAKE HotBalloon ® catheter (HBC) is a radiofrequency balloon catheter for the treatment of atrial fibrillation (AF), and was approved for use in Japan to treat drug-resistant paroxysmal AF in 2015. Post-marketing surveillance study was conducted by Toray Industries, Inc. to evaluate the efficacy and safety of HBC treatment in patients with paroxysmal AF in a real-world setting. This study is the first nation-wide survey of HBC treatment for paroxysmal AF in clinical practice in Japan., Methods and results: This was a single-arm, multicenter observational study with an observation period of 48 weeks after ablation. Pulmonary vein isolation and AF non-recurrence rates were evaluated and adverse events (AEs) were observed at 46 sites in Japan. An AF event was defined as recurrence of AF or re-ablation from 12 to 48 weeks after ablation. The success rate of pulmonary vein isolation was 99.0% (486/491) for patients with AF. The cumulative AF non-recurrence rate was 94.1% at 24 weeks and 87.8% at 48 weeks. AEs were found to occur 21.5% (114/530), and ablation-related AEs were found to occur 2.6% (14/530) during the study period, with the most common being pericardial effusion (0.8%, 4/530)., Conclusions: This study demonstrates the efficacy and safety of HBC ablation in Japanese patients with recurrent symptomatic paroxysmal AF refractory to antiarrhythmic therapy.