Prevalence and Prognostic Impact of Multiple Frailty Domain in Japanese Older Adults.

OBJECTIVES: In this observational study, we aimed to evaluate the independent and overlapping effects of multiple frailty domains on long-term care insurance (LTCI) use. DESIGN: Population-based cohort design. SETTING AND PARTICIPANTS: In total, 9804 community-dwelling older adults were recruited from the National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes. METHODS: The physical domain of frailty was assessed using the revised Japanese version of the Cardiovascular Health Study criteria. The cognitive domain of frailty was identified as impairment of memory, attention, executive function, or processing speed using standardized thresholds established for each domain in population-based cohorts. The social domain was operationalized using the National Center for Geriatrics and Gerontology-Social Frailty Scale. The use of LTCI was prospectively determined over 60 months using data extracted from the Japanese long-term care insurance system. RESULTS: The data from 7745 participants were analyzed, of whom 793 (10.2%) required LTCI certification within 60 months (interquartile range: 60-60 months). The Kaplan-Meier curve analysis demonstrated that a high number of frailty domains was associated with incident LTCI use. The proportions of incident LTCI use were 6.0%, 12.4%, 30.1%, and 43.9% for non-frail participants and those with impairments in 1, 2, and 3 frailty domains, respectively. In the multivariate Cox regression model, physical, cognitive, and social domain impairments independently increased the risk of incident LTCI use [physical domain impairment, hazard ratio (HR), 1.67; 95% CI, 1.39-2.01; cognitive domain impairment, HR, 1.59; 95% CI, 1.37-1.84; social domain impairment, HR, 1.26; 95% CI, 1.05-1.50]. CONCLUSIONS AND IMPLICATIONS: Overlapping frailty domains were strongly associated with incident LTCI use among community-dwelling older adults. These findings emphasize the importance of assessing multiple frailty domains and tailoring interventions according to the unique circumstances of older adults to prevent functional disabilities.

Validation of the Optimal University of California Los Angeles Loneliness Scale Cutoff Score in Screening for the Prevention of Disability Occurrence Among Older Japanese Adults.

OBJECTIVES: The association between loneliness and disability is a growing public health priority. While the University of California Los Angeles Loneliness Scale (UCLA-LS) has been internationally used as an indicator for assessing loneliness, its optimal cutoff point in relation to disability occurrence has not yet been examined. Therefore, we aimed to determine the optimal cutoff point of the UCLA-LS regarding future disability. METHODS: This longitudinal cohort study was conducted in Tokai City, Aichi Prefecture, Japan. Overall, 4536 community-dwelling older adults (age: 73.8 ± 5.5 years; females: 55.2%) were followed up for 2 years. The area under the curve of the receiver operating characteristic analysis was calculated to evaluate the optimal cutoff point of the UCLA-LS in relation to future disability occurrence using the Youden index, which maximized the sensitivity and specificity of the UCLAS-LS. A survival analysis was conducted to test this cutoff value's external validity, using the presence or absence of disability occurrence as the dependent variable. RESULTS: The cutoff score of the UCLA-LS in relation to future disability was 44 points. An association was found between new disability occurrence and loneliness based on this cutoff value (hazard ratio: 1.67, 95% confidence interval: 1.29-2.16). CONCLUSIONS: Although cultural context should be taken into account, the optimal cutoff scores for the loneliness scale related to disability identified in this study may be a useful indicator for early recognition of loneliness as a global public health problem and for promoting social participation as one of the disability prevention strategies.

Association between social isolation and diversity in food intake by gender in community-dwelling older adults: A cross-sectional study.

AIM: Few studies have investigated the relationship between low dietary variety and clearly defined social isolation by gender. This study explored the association between dietary variety and social isolation, classified by operational definition, separately by gender in community-dwelling older adults. METHODS: This cross-sectional study recruited respondents via mail. A total of 4798 participants aged ≥65 years participated in the on-site assessment. Social isolation was assessed by "lack of conversation," "lack of passive support," "lack of offering support," and "lack of social participation." Dietary variety was evaluated using the Dietary Variety Score (DVS). RESULTS: The participants' median age was 73 (interquartile range 25-75: 69-77) years, and 2147 (44.7%) were male. After adjusting for covariates, with regard to male participants, a lack of offering support (ß = -0.051, P = 0.019) and a lack of social participation (ß = -0.089, P < 0.001) were associated with a low DVS. For female participants, only a lack of social participation was related to a low DVS (ß = -0.067, P < 0.001). A lack of conversation and passive support were not associated with a low DVS for both genders (P >0.05). CONCLUSION: The results indicate that encouraging social participation, regardless of gender, as well as preventing a lack of offering support for others among men, may contribute to improving individuals' DVS. Geriatr Gerontol Int 2024; ••: ••-••.

Association between the level of social participation and depressive symptoms among older Japanese adults: a cross-sectional survey.

BACKGROUND: Social participation is recommended for older adults to remain actively involved in daily life. Social participation is a broad concept, ranging from 'interacting with others without doing a specific activity with them' to 'actively contributing to society.' However, previous studies have not taken into account the components of social participation. Depressive symptoms are significant outcomes in older adults. Social participation mitigates these risks owing to its association with reduced mortality and enhanced quality of life. This study aimed to examine the association between the level of social participation and depressive symptoms in community-dwelling older adults. METHODS: We included 17 040 individuals aged ≥65 years. Social participation was categorised into Level 3, interacting with others without doing a specific activity with them; Level 4, engaging in an activity with others; Level 5, helping others; and Level 6, contributing to society, based on a previous study by Levasseur et al. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale. Logistic regression models were used to examine the association between the level of social participation and depressive symptoms. RESULTS: Overall, 15 069 older adults met the inclusion criteria. A higher level of social participation was associated with lower odds ratios (ORs) for depressive symptoms (Level 6 = OR: 0.43, 95% confidence interval (CI): 0.37-0.50; Level 5 = OR: 0.50, 95% CI: 0.41-0.60; and Level 4 = OR: 0.60, 95% CI: 0.52-0.69). Subgroup analyses based on age and sex yielded similar results across all participants. CONCLUSIONS: Among older adults in Japan, a higher level of social participation was associated with lower rates of depressive symptoms. The relationship between depressive symptoms and the levels of social participation may help develop measures to reduce or prevent depressive symptoms in older adults.

Combined effects of loneliness and diabetes mellitus on disability incidence among older Japanese adults.

BACKGROUND: Developed countries worldwide face the challenge of aging populations in which loneliness is problematic, leading to mental and physical health issues. Diabetes mellitus (DM) can cause decreased physical activity, reduced functioning, and depressive symptoms. However, how interactions between loneliness and DM influence health outcomes remains unclear. We aimed to determine the effects of loneliness and DM-related complications on the incidence of disability among older individuals. METHODS: We analyzed data from the Japanese National Center for Geriatrics and Gerontology Study of Geriatric Syndromes for community-dwelling adults aged ≥65 years without initial long-term care needs. Loneliness was assessed using the University of California Los Angeles Loneliness Scale, and DM status was determined based on medical history obtained through face-to-face interviews. Disability incidence was identified by monthly tracking of certifications under the Japanese long-term care insurance system. The combined effect of DM and loneliness on care needs was examined using Cox proportional hazard regression models. RESULTS: Among 5,160 participants, 298 (5.8 %) developed incident disabilities within 24 months. Cox models adjusted for potential confounders revealed a significantly increased disability risk among persons with DM and loneliness. Having DM without loneliness and vice versa were not significant risk factors for disability incidence compared with having neither. CONCLUSIONS: The combination of loneliness with DM was a risk factor for disability development among community-dwelling older adults. Loneliness and DM might be interrelated and associated with disability development, suggesting that support along with assessments of mental health and illness might help to avoid disability in this population.

Risk of dementia with hearing impairment and social isolation.

INTRODUCTION: This study aimed to determine whether the concomitance of hearing impairment and isolation with lack of conversation, which is considered self-evident but has not been investigated extensively, is associated with the occurrence of dementia. METHODS: A total of 2745 participants were divided into four groups according to the presence/absence of hearing impairment and isolation with lack of conversation. The association of dementia with hearing impairment and isolation with lack of conversation was analyzed using Cox proportional hazards regression. RESULTS: The combined hearing impairment and isolation with lack of conversation (hazard ratio: 1.69, 95% confidence interval: 1.09-2.61) and non-hearing impairment and isolation with lack of conversation (hazard ratio: 1.60, 95% confidence: 1.07-2.39) were associated with the development of dementia. DISCUSSION: These findings emphasize the importance of promoting high-quality social relationships throughout life by adopting preventive measures against isolation with lack of conversation from the early stage of awareness of hearing impairment. Highlights: Dementia affects 12.9% of those with hearing impairment and isolation.Hearing impairment and isolation are associated with increased risk of dementia.Addressing these risk factors may help reduce the risk of developing dementia.Preventing isolation and promoting quality social relationships is important.

Development of a weighted scoring model for social activities to predict disability incidents among older Japanese adults.

BACKGROUND: Social activities contribute to health improvements in older adults, but methods for evaluating these activities are not yet established. We developed a scoring model for social activity, weighted by specific activities, to assess the association between disability incidence in older adults and social activities. METHODS: Data were obtained from Japan's National Center for Geriatrics and Gerontology Study of Geriatric Syndromes (NCGG-SGS). Social activity was evaluated across 16 domains. Disability was determined using data extracted from Japan's long-term care insurance system. RESULTS: Data from 4998 older adults were analyzed; among them, 422 (8.4 %) developed a disability within 35 months (Interquartile range: 32-39). The Cox proportional hazards model was used to assess 16 domains of social activity. The results yielded risk factors for disability incidence in six social activity domains: work, travel, hobbies, babysitting, family caregiving, and events. The coefficients for these activities were assigned weights of 3, 3, 2, 1, 1, and 1, respectively. The weighted social activity scoring model significantly improved the ability to predict disability incidence when the number of social activities in which individuals participated was considered (social activity score: area under the curve [AUC] 0.691, 95 % confidence interval [CI] 0.664-0.717; number of social activities: AUC 0.681, 95 % CI 0.654-0.707, P = 0.042). CONCLUSIONS: The composite score derived from the weighted social activity scoring model serves as a valuable tool due to its enhanced predictability, which complements established background factors associated with the incidence of disability in older adults.

Classification of social isolation and factors related to loneliness and life satisfaction among socially isolated individuals.

PURPOSE: To operationally divide social isolation into four categories and examine the factors associated with social isolation and its relationship with loneliness and life satisfaction. METHODS: The participants were community-dwelling older adults aged ≥ 60 years who underwent functional health examinations in Chita City, Aichi, Japan. Multiple regression analysis was used to examine the associations between social isolation, loneliness, and life satisfaction. RESULTS: A total of 5,066 participants (mean age 72.0 ± ± 6.3 years, female: 55.4 %) were included in the study. Multiple regression analysis showed that the number of experiences of social isolation, classified into four categories, was positively correlated with loneliness (ß = 0.188, ΔR2 = 0.244, p < 0.001) and negatively correlated with life satisfaction (ß = -0.076, ΔR2 = -0.178, p < 0.001). CONCLUSIONS: Multiple experiences of social isolation classified into four categories were found to be associated with higher loneliness and lower life satisfaction.

Rapid and reliable hybridoma screening method that is suitable for production of functional structure-recognizing monoclonal antibody.

Monoclonal antibodies are extremely valuable functional biomaterials that are widely used not only in life science research but also in antibody drugs and test drugs. There is also a strong need to develop high-quality neutralizing antibodies as soon as possible in order to stop the rapid spread of new infectious diseases such as the SARS-CoV-2 virus. This study has developed a membrane-type immunoglobulin-directed hybridoma screening (MIHS) method for obtaining high-quality monoclonal antibodies with high efficiency and high speed. In addition to these advantages, this paper demonstrates that the MIHS method can selectively obtain monoclonal antibodies that specifically recognize the functional structure of proteins. The MIHS method is a useful technology that greatly contributes to the research community because it can be easily introduced in any laboratory that uses a flow cytometer.

Coxfa4l3, a novel mitochondrial electron transport chain Complex 4 subunit protein, switches from Coxfa4 during spermatogenesis.

We identified Coxfa4l3, previously called C15orf48 or Nmes1, as a novel accessory protein of Complex IV of the mitochondrial electron transport chain (ETC). Amino acid sequence comparison, the intracellular localization and the protein expression data showed that the protein is the third isoform of Coxfa4 and the expression of Coxfa4 and Coxfa4l3 proteins during spermatogenesis showed a mutually exclusive pattern, implying that Coxfa4 replaces Coxfa4l3 in Complex IV after meiosis. These results may provide some insight into the unique mechanism of ATP production in late spermatogenesis.

Flow cytometry-based method for rapid and high-throughput screening of hybridoma cells secreting monoclonal antibody.

Monoclonal antibodies (mAbs) are a valuable biomaterial for basic life sciences and industrial purposes. The production of the mAb is time and effort intensive. In this report, we established a time- and labor-saving method for the mAb production. Because membrane-type immunoglobulin on a hybridoma cell surface and its secreted form, called as antibody, share the same binding property to the antigen, the fluorescence-labeled antigen bound to membrane-type immunoglobulin can be used as a screening marker. In the method, a hybridoma labeled by a fluorescent antigen was selected and sorted singly into 96-well plate using flow cytometer. Model experiments indicated that the method is highly efficient to obtain good mAbs suitable for Western blotting and immunofluorescence. Notably, most mAbs established by this method belonged to the IgG isotype, which is preferred over the IgM counterpart. Using a high-throughput flow cytometer, the method avoids tedious repeated screening and cloning processes. Because the method uses conventional myeloma for cell fusion and all reagents required in this method are commercially available, all research laboratories can apply the method to obtain mAbs efficiently.

Comparison between Ki67 labeling index determined using image analysis software with virtual slide system and that determined visually in breast cancer.

BACKGROUND: In recent papers, Ki67 labeling index (LI) has been used to classify breast cancer patients into the low and high Ki67LI groups for comparison studies, which showed significant differences in many prognostic factors. It has not been clarified whether image analysis software can be used for calculating LI in breast cancer. In our study, we examined whether Ki67LI in breast cancer calculated using image analysis software correlates with that measured on the basis of visual. METHODS: Fifty patients were randomly selected among breast cancer patients who underwent surgical operation from March, 2010 to May, 2010 in our hospital without preoperative chemotherapy. In this study, for the virtual slide system (VSS: VS120-L100, Olympus, Tokyo, Japan), the high-resolution VSs of all the 50 patients were prepared as samples. The image analysis software use for calculating LI was Tissuemorph Digital Pathology (Tissuemorph DP: Visiopharm, Hoersholm, Denmark). The calculated LI was extracted from 3 to 5 views containing hot spots. The LI calculated using Tissuemorph DP was designed as LI/image/T. The digital image of 3 to 5 LI/image/T views was printed out, and on the digital photograph, we counted visually the number of Ki67-immunopositive cells in exactly the same area, and the percentage of Ki67-immunopositive cells was designed as LI/direct. Moreover, a pathologist's assistant (PA) determined the tumor area in the same specimen using VSS and calculated LI using Tissuemorph DP, which was designed as LI/image/PA. The chief pathologist (CP) similarly calculated LI which was designed as LI/image/CP. We evaluated the degree of agreement between different data sets "LI/image/T and LI/direct" and "LI/image/T, LI/image/CP, and LI/image/PA" by using interclass correlation coefficient (ICC). RESULTS: The average counts of cells were as follows: LI/direct, 3209.7 ± 1970.4 (SD); LI/image/T, 2601.6 ± 1697.1; LI/image/PA, 2886.5 ± 2027.5; LI/image/CP, 18805.5 ± 22293.4. The values of LI/direct and LI/image/T showed almost perfect agreement as showed by an ICC of 0.885 (95 % CI, 0.806-0.933; p < 0.001). The agreement among three investigators was almost perfect. The obtained ICC was 0.825 (95 % CI, 0.739-0.890; p < 0.001) among the data of LI/image/T, LI/image/CP and LI/image/PA. There were five cases that immunopositivity for Ki67 showed a more than 10 % disagreement between LI/direct and LI/image/T. CONCLUSION: The merits of calculating Ki67 LI using Tissuemorph DP are as follows. First, the staining intensity of the cells to be counted can be adjusted. Second, the portion of a tumor including "hot spots" for counting can be chosen. Third, many cancer cells can be counted more rapidly using Tissuemorph DP than by visual observation. However, it is important that pathologist should check and carry out the final decision of the data, when Ki67 LI using Tissuemorph DP is calculated.

The evolution of spatial ordering of oil drops fast spreading on a water surface.

The design of dynamically self-assembled systems is of high interest in science and technology. Here, we report a unique cascade in the self-ordering of droplets accompanied by a dewetting transition. The dynamic self-emergent droplets are observed when a thin liquid layer of an immiscible fluorocarbon oil (perfluorooctyl bromide, PFOB) is placed on a water surface. Due to the gradual evaporation of PFOB, a circular PFOB-free domain appears as a result of a local dewetting transition. A circular pearling structure is generated at the rim with the growth of the dewetting hole. As the next stage, linear arrays of droplets are generated in a radial manner from the centre of the hole. These one-dimensional arrangements then evolve into two-dimensional hexagonal arrays of microdroplets through collective rhythmical shrinking/expanding motions. The emergence of such dynamic patterns is discussed in terms of the nonlinear kinetics of the dewetting transition under thermodynamically dissipative conditions.

Dysregulation of glucose, insulin, triglyceride, blood pressure, and oxidative stress after an oral glucose tolerance test in men with abdominal obesity.

Postprandial metabolic dysregulation plays a role in the development of atherosclerosis. Visceral fat accumulation is an important component of various metabolic disorders including glucose intolerance, dyslipidemia, and hypertension, which correlate with atherosclerotic cardiovascular disease. The aim of the present study was to compare the postprandial response of various metabolic parameters, blood pressure, adiponectin, and oxidative stress to 75-g oral glucose tolerance test (OGTT) in men with (n = 23) and without (n = 7) abdominal obesity based on waist circumference (WC) cutoff value of 85 cm (based on the Japanese criteria for the metabolic syndrome). The cross-sectional prospective study included 30 male subjects who were on no medications and newly diagnosed with mild hypertension and/or dyslipidemia. The percentage change in each parameter ([each parameter at 120 minutes after an OGTT - that before an OGTT]/that before an OGTT x 100) was calculated. The percentage systolic blood pressure, percentage diastolic blood pressure, and percentage triglyceride were -6.3% +/- 3.5%, -9.4% +/- 3.0%, and -10.2% +/- 2.1%, respectively, in the WC less than 85 group (vs baseline: P = .10, P < .01, and P < .001) and 2.0% +/- 1.7%, 0.9% +/- 2.4%, and 2.8% +/- 3.3%, respectively, in the WC at least 85 group (vs WC <85 group: P < .05, each). However, there were no significant differences in percentage total cholesterol and percentage high-density lipoprotein cholesterol between the 2 groups. The percentage thiobarbituric acid-reacting substances tended to be lower in the WC less than 85 group (vs baseline: P = .07), but not in the WC at least 85 group, albeit statistically insignificant (WC <85 vs >/=85 group: P = .057). The maximum carotid intima-media thickness was larger in the WC at least 85 group than the WC less than 85 group (P < .05). Evaluation of postprandial changes in obesity-related parameters may be important in preventing atherosclerotic diseases.