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High salt conditions and subsequent hyperosmolarity are injurious cellular stresses that can activate immune signaling. Nuclear factor of activated T-cells 5 (NFAT5) is an essential transcription factor that induces osmoprotective genes such as aldose reductase (AR) and betaine-GABA transporter 1 (BGT1). High salt stress-mediated NFAT5 activation is also reported to accelerate the inflammatory response and autoimmune diseases. However, the systemic regulation of NFAT5 remains unclear. Here, we performed a genome-wide siRNA screen to comprehensively identify the regulators of NFAT5. We monitored NFAT5 nuclear translocation and identified one of the Notch signaling effectors, Hairy and enhancer of split-1 (HES1), as a positive regulator of NFAT5. HES1 was induced by high salinity via ERK signaling and facilitated NFAT5 recruitment to its target promoter region, resulting in the proper induction of osmoprotective genes and cytoprotection under high salt stress. These findings suggest that, though HES1 is well known as a transcriptional repressor, it positively regulates NFAT5-dependent transcription in the context of a high salinity/hyperosmotic response., (© 2024. The Author(s).)

Extracellular signal-regulated kinase (ERK) signaling is essential to regulated cell behaviors, including cell proliferation, differentiation, and apoptosis. The influence of cell-cell contacts on ERK signaling is central to epithelial cells, yet few studies have sought to understand the same in cancer cells, particularly with single-cell resolution. To acquire same-cell measurements of both phenotypic (cell-contact state) and targeted-protein (ERK phosphorylation) profiles, we prepend high-content, whole-cell imaging prior to end-point cellular-resolution Western blot analyses for each of hundreds of individual HeLa cancer cells cultured on that same chip, which we call contact Blot. By indexing the phosphorylation level of ERK in each cell or cell cluster to the imaged cell-contact state, we compare the ERK signaling between isolated and in-contact cells. We observe attenuated (∼2×) ERK signaling in HeLa cells that are in-contact versus isolated. Attenuation is sustained when the HeLa cells are challenged with hyperosmotic stress. Our findings show the impact of cell-cell contacts on ERK activation with isolated and in-contact cells while introducing a multi-omics tool for control and scrutiny of cell-cell interactions.

Extracellular signal-regulated kinase (ERK) signaling is essential to regulated cell behaviors, including cell proliferation, differentiation, and apoptosis. The influence of cell-cell contacts on ERK signaling is central to epithelial cells, yet few studies have sought to understand the same in cancer cells, particularly with single-cell resolution. To acquire same-cell measurements of both phenotypic (cell-contact state) and targeted-protein profile (ERK phosphorylation), we prepend high-content, whole-cell imaging prior to endpoint cellular-resolution western blot analyses for each of hundreds of individual HeLa cancer cells cultured on that same chip, which we call contact Blot. By indexing the phosphorylation level of ERK in each cell or cell-cluster to the imaged cell-contact state, we compare ERK signaling between isolated and in-contact cells. We observe attenuated (~2×) ERK signaling in HeLa cells which are in-contact versus isolated. Attenuation is sustained when the HeLa cells are challenged with hyperosmotic stress. Our findings show the impact of cell-cell contacts on ERK activation with isolated and in-contact cells, while introducing a multi omics tool for control and scrutiny of cell-cell interactions.

Background: While rapid population ageing is occurring worldwide, its speed is especially prominent in Asian countries. In Asia, cultural diversity might significantly affect care burden; however, few studies have investigated the differences in care burden, and mental, physical and social conditions among Asian countries. This study aimed to clarify the situations of and differences in family caregivers (FCs) of older persons in Japan and Thailand, and evaluate the factors associated with care burden in both countries., Methods: A cross-national survey of 217 in-home FCs was conducted in Japan and Thailand and mainly included items regarding care burden and psychosocial conditions. Differences between the two countries were obtained, and the factors associated with care burden were analysed by multiple regression analyses., Results: The FCs' and care receivers' mean ages (64.8 ± 11.1 and 84.8 ± 8.6 years, respectively) in Japan were significantly higher than the mean ages (49.1 ± 13.3 and 77.1 ± 9.5 years) in Thailand. In Japan, FCs had more severe care burden, loneliness, and stress compared to those in Thailand. In Thailand, FCs had more social connections and informal support than those in Japan. The factors associated with care burden were different in each country; thus, severe stress, low emotional care preparation, and low willingness to continue care at home were significantly associated with severe care burden in Japan, whereas poor relationships with care receivers, few social connections, low confidence in providing care, low emotional care preparation, and lack of informal support were significantly associated with severe care burden in Thailand., Conclusions: Despite there being a long-term care insurance system in Japan, which is absent in Thailand, care burden and psychosocial conditions of FCs might be worse in Japan. There was a clear difference in the factors associated with care burden between Japan and Thailand., (© 2024 Japanese Psychogeriatric Society.)

Aim: To understand whether the sleep quality of the caregivers of elderly inpatients is associated with their own characteristics and with the characteristics or sleep quality of the elderly inpatients., Design: A cross-sectional study design that recruited participants from September to December 2020 was adopted, in which 106 pairs of elderly inpatients and caregivers were recruited., Methods: Data collected from the elderly inpatients included demographic characteristics as well as the numerical rating scale (NRS) score, Charlson Comorbidity Index (CCI), Geriatric Depression Scale Short Form (GDS-SF) score, and Pittsburgh Sleep Quality Index (PSQI). Caregiver data included demographic characteristics and PSQI., Results: In the regression analysis of caregiver characteristics and caregiver sleep quality, only caregiver age and the relationship between caregiver and inpatient (other vs. spouse) were correlated with caregiver sleep quality. In the regression analysis of elderly inpatient characteristics, caregiver characteristics, and caregiver sleep quality, only the PSQI of elderly inpatients and the relationship between caregiver and inpatient (other vs. spouse) were correlated with caregiver sleep quality., Patient or Public Contribution: Poor caregiver sleep quality was more likely to manifest when the elderly inpatients had poor sleep quality, when the caregivers themselves were older, and when the caregiver was the inpatient's spouse., (© 2023 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

This study aimed to evaluate the effects of a virtual reality intervention for dementia care education in Japanese acute care nurses. Non-randomised controlled trial was used to assess the effectiveness of the intervention pre- and post-intervention and at a 1-month follow-up. This study enrolled 20 and 19 nurses in the intervention and control groups, respectively. Generalized estimating equation analyses revealed significant differences in scores on the Dementia Nursing Competency Scale in Acute Hospitals and Staff Experiences of Working with Dementia Residents questionnaire in the intervention group. A post hoc test revealed significantly higher scores on the Dementia Nursing Competency Scale in Acute Hospitals at 1 month after compared with pre-intervention. Staff Experiences of Working with Dementia Residents questionnaire scores were significantly lower at pre- than that at post-intervention and 1 month after intervention. These findings could improve competency of dementia nursing care and attitudes toward people with dementia., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Type 2 diabetes mellitus (T2DM), common in older people, is an important reason for muscle loss in Japanese and Taiwanese populations. However, little is known about the association between lifestyle behaviours and muscle quality. We aimed to compare the lifestyle behaviours of Japanese and Taiwanese older adults with T2DM and to the identify lifestyle factors associated with muscle quality., Methods: This cross-sectional study was conducted among community-dwelling individuals with T2DM aged ≥65 years in Taiwan and Japan. Totally, 114 Japanese and 226 Taiwanese participants were enrolled in the study. Outcomes were measured by blood biochemical examinations, body composition analyses and structured self-reported questionnaires to assess lifestyle behaviours and muscle quality. Linear regression models were used to examine the relationship between lifestyle factors and muscle quality using SPSS version 27.0 with a statistical significance level of P < 0.05., Results: Japanese subjects were more likely to be smokers and alcohol consumers, and they were less likely to have well-balanced diets and engage in more physical activity as compared to Taiwanese subjects. The muscle quality in the Japanese subjects was significantly poorer than that in the Taiwanese subjects. Physical activity, dietary habits and smoking were associated with muscle quality, after adjusting for age, gender and body mass index., Conclusions: Physical activity of insufficient intensity, unhealthy dietary habits and smoking could be risk factors for poor muscle quality. These findings can contribute to the development of effective strategies to improve muscle quality in community-dwelling older Asian people with T2DM., (© 2022 Japanese Psychogeriatric Society.)

Aim and Objectives: The purpose of this study was to investigate which factors are associated with the quality of dementia care in acute care hospitals., Background: The number of people with dementia who are admitted to acute care hospitals is increasing. Improving the quality of dementia care in acute care hospitals is an important issue. Prior studies have demonstrated that not only knowledge and nursing experience, but also psychological factors and the nursing practice environment are related to high-quality care on general wards., Design: Cross-sectional hypothesis-testing design., Methods: Participants were nurses providing care to people with dementia at acute care hospitals. Questionnaires were distributed to 300 acute care hospitals in Japan, 10 copies each and 773 valid responses were received. Based on the hypothesis model, variables were tested using multiple regression analysis. The model described the relationship between quality of care, personal attributes and the nursing practice environment. The Strengthening the Reporting of Observational Studies in Epidemiology checklist was used., Results: Almost 90% of the study sample was female, the mean age was 37.4 ± 9.3 years, and the mean nursing experience was 14.0 ± 8.7 years. The results showed that nursing foundations for quality of care, staffing and resource adequacy, specialist consultation, promoting systematic recreation and exchange, knowledge, and feelings towards people with dementia were associated with the quality of dementia care in acute care hospitals. The adjusted coefficient of determination was 0.367., Conclusion: This study identified factors associated with the quality of dementia care in acute care hospitals. Knowledge and feelings towards people with dementia are important, and the nursing practice environment plays an important role in improving the quality of dementia care., Relevance to Clinical Practice: Not only improving nurse's practical ability but also a supportive nursing practice environment enhances the quality of dementia care in acute care hospitals., (© 2021 John Wiley & Sons Ltd.)

Aim: The aim of this study was to clarify the association between dietary protein intake and decline in the estimated glomerular filtration rate (eGFR) among Japanese older adults., Methods: We used the data of the Septuagenarians, Octogenarians and Nonagenarians Investigation with Centenarians (SONIC) study, an ongoing narrow-age range cohort study: 69-71 years, 79-81 years and 89-91 years. The outcome variable, change in eGFR, was estimated from serum creatinine measured at the baseline and 3-year follow up, and the exposure variable, protein intake, was calculated using the brief-type self-administered diet history questionnaire at the baseline. Associations between eGFR change and protein intake were determined by multiple linear regression analysis., Results: The mean eGFR change per year was -1.89 mL/min/1.73 m 2 . The mean protein intake was 1.50 g/kg/day. The results of this study showed that there was no significant association between protein or animal protein intake and change in eGFR per year in the entire population of participants, including the very elderly, but there was a significant positive association in those whose renal function fell into chronic kidney disease stage G3 or G4., Conclusions: Protein intake among community-dwelling older adults was not associated with lower eGFR, and for older chronic kidney disease patients, protein and animal protein intakes were more beneficial in maintaining eGFR. The results provide evidence that protein intake should not be restricted for older patients with chronic kidney disease, including the very elderly. Geriatr Gerontol Int 2022; 22: 286-291., (© 2022 The Authors. Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Objective: To examine the effect of employment status on sleep, care burden, and negative affect among family caregivers (FCs) at home., Methods: An intensive longitudinal design was applied in which 25 FCs underwent in-home assessments for up to 56 days. At baseline, demographic data and employment status were collected. FCs wore a wrist-worn device with an accelerometer to assess objective total sleep time (TST) for consecutive 24-hour periods. FCs answered the Zarit Burden Interview (ZBI) and Positive and Negative Affect Schedule (PANAS) every night before sleep. Linear mixed model analysis was used to examine the effect of objective sleep status on ZBI and PANAS scores the following day., Results: Mean participant age was 66.3 ± 10.8 years (72.0% female), and mean survey period was 29.1 ± 9.6 days (866 observations). Mean TST of FCs was 5.7 ± 1.4 hours. In total, 32.0% of FCs were employed either full- or part-time. TST of employed FCs was significantly associated with care burden and negative affect (B = -0.4 and -1.3, respectively); however, positive affect was not associated with TST. FCs who were unemployed experienced less care burden and negative affect (rate of change: -7.7 and -8.0, respectively). Additionally, TST of unemployed FCs was associated with negative affect; thus, when they slept 1 hour longer than their mean TST, they experienced less negative affect the following day., Conclusion: A reduction in TST could lead to increased care burden and more severe negative affect the following day, which may be moderated by employment status.

Tumor metastasis is the leading cause of death worldwide and involves an extremely complex process composed of multiple steps. Our previous study demonstrated that apoptosis signal-regulating kinase 1 (ASK1) deficiency in mice attenuates tumor metastasis in an experimental lung metastasis model. However, the steps of tumor metastasis regulated by ASK1 remain unclear. Here, we showed that ASK1 deficiency in mice promotes natural killer (NK) cell-mediated intravascular tumor cell clearance in the initial hours of metastasis. In response to tumor inoculation, ASK1 deficiency upregulated immune response-related genes, including interferon-gamma (IFNγ). We also revealed that NK cells are required for these anti-metastatic phenotypes. ASK1 deficiency augmented cytokine production chemoattractive to NK cells possibly through induction of the ligand for NKG2D, a key activating receptor of NK cells, leading to further recruitment of NK cells into the lung. These results indicate that ASK1 negatively regulates NK cell-dependent anti-tumor immunity and that ASK1-targeted therapy can provide a new tool for cancer immunotherapy to overcome tumor metastasis., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

We investigated the association of systolic blood pressure (SBP) level with physical frailty and cognitive function in community-dwelling older Japanese. Using the 'Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians' survey as the baseline, we performed a cross-sectional analysis of people aged 70 ± 1 (n = 1000), 80 ± 1 (n = 978), and 90 ± 1 (n = 272) years. Medical histories and medications were collected via interviews conducted by medical professionals. Blood pressure (BP), grip strength, gait speed, and cognitive function were examined on site. Trend analysis and multiple regression analysis were used to determine the association of the SBP level with physical frailty and cognitive function. The principal finding was that the association of SBP with physical frailty and cognitive function varied depending on characteristics such as age, physical and cognitive function, and antihypertensive medication use. A lower SBP level was associated with a higher prevalence of physical frailty only among 80-year-olds who were on antihypertensive medication. A significant association was found between higher SBP and lower cognitive function among 70-year-olds, while among 90-year-olds, the opposite was found. No association was found among participants who were 80 years old or among participants of all ages without antihypertensive medication. Our finding that an inverted association between SBP and geriatric syndrome exists suggests that the treatment of older patients must be individualized to prevent geriatric syndrome.

One of the fundamental processes in morphogenesis is dome formation, but many of the mechanisms involved are unexplored. Previous in vitro studies showed that an osmotic gradient is the driving factor of dome formation. However, these investigations were performed without extracellular matrix (ECM), which provides structural support to morphogenesis. With the use of ECM, we observed that basal hypertonic stress induced stable domes in vitro that have not been seen in previous studies. These domes developed as a result of ECM swelling via aquaporin water transport activity. Based on computer simulation, uneven swelling, with a positive feedback between cell stretching and enhanced water transport, was a cause of dome formation. These results indicate that osmotic gradients induce dome morphogenesis via both enhanced water transport activity and subsequent ECM swelling., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Aim: Several studies have reported a negative correlation between depressive symptoms and family caregivers' (FCs) subjective sleep status. However, there is a paucity of information on the association between objective/subjective sleep status, care burden, and related factors., Methods: Participants were 23 pairs of care receivers (CRs; M age = 82.7 ± 8.5 years; 69.6% women) receiving long-term care at home and their FCs (M age = 66.9 ± 11.0 years; 69.6% women). At baseline, demographic data, subjective sleep status (Pittsburgh Sleep Quality Index; PSQI), WHO-5 well-being, depressive mood, and frequency of going outdoors were collected. FCs wore a small, wrist-worn device with an accelerometer to assess objective sleep status for a consecutive 24-h 2-week period, and they answered the Zarit Burden Interview short version (ZBI) every night before sleep. After 3 months, CR status was collected and analysed retrospectively., Results: The mean total sleep time over 2 weeks was 349.5 ± 69.6 min. The mean ZBI score over 2 weeks was 8.8 ± 6.8, which was significantly correlated with total sleep time (r = -0.42; P < 0.05), total time in bed (r = -0.44; P < 0.05), PSQI (r = 0.62; P < 0.01), frequency of going outdoors by CRs (r = -0.42; P < 0.05), and WHO-5 well-being among CRs (r = -0.50; P < 0.05). Multiple regression analyses revealed that total sleep time (β = -0.51; P < 0.05) was significantly associated with care burden (adjusted R 2 = 0.45). At the 3-month follow-up, four CRs had been hospitalised or died, and their FCs displayed significantly severe care burden and slept less than at baseline., Conclusions: Reduced objective total sleep time is significantly associated with the severity of care burden among FCs. Home-based care is critical in Japan; therefore, it is meaningful to determine how to reduce care burden., (© 2020 The Authors Psychogeriatrics published by John Wiley & Sons Australia, Ltd on behalf of Japanese Psychogeriatric Society.)

Aim: The objective of this study was to clarify the relationship between cognitive function and the serum albumin/globulin ratio (A/G ratio) in community-dwelling Japanese older adults., Methods: Randomly extracted residents in both urban and rural parts of Japan were enrolled in this study. A total of 1827 participants with a mean age of 70 or 80 years were recruited. A venue survey method was carried out with comprehensive studies, including interviews, blood collection, physical examination and cognitive function tests., Results: Univariate analysis showed a significant positive correlation between the total Japanese version of the Montreal Cognitive Assessment score and the serum A/G ratio at the age of 70 and 80 years, in which better cognitive function was associated with a high serum A/G ratio. Multiple regression analysis with the total Japanese version of the Montreal Cognitive Assessment score as the dependent variable showed that the serum albumin level, serum globulin level, serum A/G ratio, C-reactive protein, years of formal education and sex were related to the Japanese version of the Montreal Cognitive Assessment total score at the age of 70 years, and that the serum albumin level, serum globulin level, serum A/G ratio, C-reactive protein, years of formal education and stroke were related at the age of 80 years. The serum A/G ratio showed a better correlation than the serum globulin levels at the age of 70 and 80 years (70 years: β = 0.131 vs -0.111, 80 years: β = 0.108 vs -0.071)., Conclusions: We found a correlation between cognitive function and the serum A/G ratio in community-dwelling older people, suggesting that nutritional status and chronic inflammation might influence cognitive function. Geriatr Gerontol Int 2019; 19: 967-971., (© 2019 Japan Geriatrics Society.)

Aim: To critically analyse the concept of dementia nursing competency in acute care settings., Backgrounds: The nursing care needs of patients with dementia are increasing in acute care settings. However, a framework for the dementia nursing competency has not been explicitly outlined., Design: Rodgers' evolutionary method for concept analysis., Data Sources: Competenc* AND dementia AND nurs* AND acute OR hospital OR clinical were selected from the MEDLINE, CINAHL, PsycINFO, CiNii, and Google Scholar for publication from 2006 to 2017., Review Methods: All 29 articles were identified. Data were analysed with a particular focus on the attributes, antecedents, and consequences of the concept., Results: Six attributes were identified: respecting patient individuality, applying ethical considerations, providing person-centred care, possessing responsibility, coordinating external environments, and possessing care coordination and facilitation skills. Identified antecedents included building theoretical and clinical knowledge, developing an awareness of dementia and its risk behaviours, performing assessments of dementia nursing practice, developing relationships with patients with dementia, and applying a team approach. Applying the competency led to positive consequences for patients, nurses, and patient-nurse and nursing team relationships., Conclusion: Developing the dementia nursing competency results in stronger emotional interventions and adds a human-to-human connection., (© 2019 John Wiley & Sons Australia, Ltd.)

Staphylococcus aureus formed bacterial aggregates in the plasma fraction of the hemolymph of silkworm, the larva of Bombyx mori, in a growth-dependent manner. The addition of arabinose or galactose inhibited the formation of S. aureus aggregates in the silkworm plasma. Formation of the bacterial aggregates depended on S. aureus genes required for the synthesis of bacterial surface polysaccharides-ypfP and ltaA, which are involved in lipoteichoic acid synthesis, and the tagO gene, which is involved in wall teichoic acid synthesis. These findings suggest that S. aureus forms bacterial aggregates in the silkworm plasma via bacterial surface teichoic acids., Competing Interests: The authors have declared that no competing interests exist.

Home visit nurses (HVNs) are crucial in psychiatric home visit nursing (PHVN) in Japan. However, little is known about violence toward HVNs in PHVN and non-PHVN settings. The current study aimed to clarify nurses' experiences of violence in these settings, their implementation of preventive measures, and related associations. Questionnaires were distributed to HVNs who provided PHVN and non-PHVN services. Sixty-nine (38%) of 184 participants had experienced at least one form of violence during the past 12 months, and 87 (47%) had experienced violence during their PHVN career. In non-PHVN settings, violence was experienced by 94 (51%) participants in the past 12 months and 119 (65%) participants during their career. Low use of preventive measures was found. The management of visiting schedules and confirmation of HVNs' locations during visits were negatively associated with exposure to violence in PHVN settings. It is important to promote measures to prevent high exposure to violence, emphasize the monitoring of visits, and have nursing agencies clarify HVNs' concerns in PHVN settings. [Journal of Psychosocial Nursing and Mental Health Services, 57(4), 40-48.]., (© 2018 Fujimoto, Greiner, Hirota, Yamaguchi, Ryuno, Hashimoto.)

Background: Chronic and lifestyle-related diseases and social status were reported to be associated with long-term care (LTC). The social factors should be treated as social sub-groups of which characteristics show social profiles. However, few previous studies considered that. The present study aimed to investigate the associations between LTC and chronic and lifestyle-related diseases, and whether the associations were modified by the social sub-groups in the community-dwelling elderly., Method: A cross-sectional study was conducted among 1004 community-dwelling participants aged 80 and 90. LTC was used as the outcome. Chronic and lifestyle-related diseases (i.e., stroke, heart disease, joint pain, osteoporosis, lung disease, cancer, hypertension, dyslipidemia, and diabetes) were used as the predictors. Education, household income, residential area, and support environment were analyzed by latent class analysis (LCA) to derive social profiles. We obtained odds ratios (ORs) of LTC from those diseases and tested interactions between those diseases and the social profiles by logistic regression analyses., Result: The participants were categorized into two sub-groups of social factors (n = 675 and 329) by LCA. Logistic regression analyses showed ORs (95% CI) of LTC were 4.69 (2.49, 8.71) from stroke, 2.22 (1.46, 3.38) from joint pain, 1.99 (1.22, 3.25) from osteoporosis, and 2.05 (1.22, 3.40) from cancer adjusting for the social sub-groups. There were no significant interactions between the social subgroups and those diseases in relation to LTC except for osteoporosis., Conclusion: The associations between LTC and chronic and lifestyle-related diseases were significant with adjusting for the social sub-groups, and not modified by that except osteoporosis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Growing evidence suggests that oral health may be an important factor associated with cognitive function in aged populations. However, many previous studies on this topic used insensitive oral indicators or did not include certain essential covariates. Thus, we examined the association between occlusal force and cognitive function in a large sample of older adults, controlling for dietary intake, vascular risk factors, inflammatory biomarkers, depression, and genetic factors., Methods: In this cross-sectional study of older community-dwelling Japanese adults, we examined data collected from 994 persons aged 70 years and 968 persons aged 80 years. Cognitive function was measured using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). Oral status and function were evaluated according to the number of remaining teeth, periodontal pocket depth, and maximal occlusal force. Associations between MoCA-J scores and occlusal force were investigated via bivariate and multivariate analyses., Results: Education level, financial status, depression score, and intake of green and yellow vegetables, as well as number of teeth and occlusal force, were significantly correlated with MoCA-J scores in both age groups. Among individuals aged 80 years, CRP and periodontal status were weakly but significantly associated with MoCA-J score. After controlling for all significant variables via bivariate analyses, the correlation between maximal occlusal force and cognitive function persisted. A path analysis confirmed the hypothesis that cognitive function is associated with occlusal force directly as well as indirectly via food intake., Conclusions: After controlling for possible factors, maximal occlusal force was positively associated with cognitive function directly as well as indirectly through dietary intake.

Cancer is a major problem in public health and is one of the leading causes of mortality worldwide. Many types of cancer cells exhibit aberrant cellular signal transduction in response to stress, which often leads to oncogenesis. Mitogen-activated protein kinase (MAPK) signal cascades are one of the important intracellular stress signaling pathways closely related to cancer. The key molecules in MAPK signal cascades that respond to various types of stressors are apoptosis signal-regulating kinase (ASK) family members; ASK1, ASK2 and ASK3. ASK family members are activated by a wide variety of stressors, and they regulate various cellular responses, such as cell proliferation, inflammation and apoptosis. In this review, we will discuss both the oncogenic and anti-oncogenic roles of the ASK family members in various contexts of cancer development with deeper insights into the involvement of ASK family members in cancer pathology., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aim: Previous literature has found positive correlations between social capital and health in older adults, fewer studies have investigated the subdimension's effects of social capital on health. We aimed to determine the individual social capital subfactors in community-dwelling older adults in Japan, and to analyze the associations of these factors with physical and mental health., Method: We sent a self-administered questionnaire assessing their perception of social group activity as the individual social capital, and mental and physical health (measured by the Medical Outcomes Study Short Form-36) to 4320 randomly selected older people., Results: There were 1836 valid responses. We clarified that people who participated in any social activity group were in significantly better physical and mental health compared with the people who did not. By the factor analysis of the perception for the social group activity, we identified three components of the individual social capital aspect that we termed harmonious, hierarchic and diversity. Using multiple linear regression, we found the hierarchic aspect was significantly negatively associated with mental health, whereas the harmonious aspect was significantly positively associated with mental and physical health, and diversity was significantly positively associated with mental health., Conclusion: As the previous research literature on social capital has mainly emphasized its positive health consequences, the present findings provide a novel demonstration that some aspects of individual social capital can have negative associations with health outcomes in community-dwelling older people. For the practical application of promoting a healthier society, it is important to consider both the positive and negative sides of social capital. Geriatr Gerontol Int 2017; 17: 2427-2434., (© 2017 Japan Geriatrics Society.)

Both hypertension and diabetes in middle-aged individuals have been suggested to be predictive indicators of cognitive decline. However, the association of hypertension, diabetes and their combination with cognitive functioning is still controversial in older people. The purpose of this study was to investigate the association between cognitive decline and hypertension, diabetes, and their combination in 70-year-old people based on a 3-year longitudinal analysis. Four hundred and fifty-four people aged 70 (±1) years who participated in the Japanese longitudinal cohort study of Septuagenarians, Octogenarians and Nonagenarians Investigation with Centenarians (SONIC) were recruited randomly from a general population and were monitored for 3 years. The data, including most of the demographics, cognitive functioning measured by the Montreal Cognitive Assessment Japanese version (MoCA-J), blood pressure, blood chemistry and other medical histories, were collected at baseline and during the follow-up. The prevalence of hypertension noted in the follow-up survey was significantly higher than than noted at baseline. The mean MoCA-J score at follow-up was not significantly different from the score obtained at baseline. However, the participants with diabetes, especially combined with hypertension at baseline, had significantly lower MoCA-J scores than those without lifestyle-related diseases. The combination of hypertension and diabetes was still a significant risk factor for cognitive decline, considering the MoCA-J scores obtained during the follow-up after adjustments at baseline, relative to sex, body mass index, dyslipidemia, smoking, excessive alcohol intake, antihypertensive treatment and education level (β=-0.14; P<0.01). Our findings indicate that diabetes and the combination of hypertension and diabetes are clear risk factors for future cognitive decline in elderly individuals who are 70 years of age.

Background: The minor alleles of 3 FOXO3 single nucleotide polymorphisms (SNPs)- rs2802292 , rs2253310 , and rs2802288 -are associated with human longevity. The aim of the present study was to test these SNPs for association with blood pressure (BP) and essential hypertension (EHT)., Methods: In a primary study involving Americans of Japanese ancestry drawn from the Family Blood Pressure Program II we genotyped 411 female and 432 male subjects aged 40-79 years and tested for statistical association by contingency table analysis and generalized linear models that included logistic regression adjusting for sibling correlation in the data set. Replication of rs2802292 with EHT was attempted in Japanese SONIC study subjects and of each SNP in a meta-analysis of genome-wide association studies of BP in individuals of European ancestry., Results: In Americans of Japanese ancestry, women homozygous for the longevity-associated (minor) allele of each FOXO3 SNP had 6mm Hg lower systolic BP and 3mm Hg lower diastolic BP compared with major allele homozygotes (Bonferroni corrected P < 0.05 and >0.05, respectively). Frequencies of minor allele homozygotes were 3.3-3.9% in women with EHT compared with 9.5-9.6% in normotensive women ( P = 0.03-0.04; haplotype analysis P = 0.0002). No association with BP or EHT was evident in males. An association with EHT was seen for the minor allele of rs2802292 in the Japanese SONIC cohort ( P = 0.03), while in European subjects the minor allele of each SNP was associated with higher systolic and diastolic BP., Conclusion: Longevity-associated FOXO3 variants may be associated with lower BP and EHT in Japanese women.

We identified SA1684 as a Staphylococcus aureus virulence gene using a silkworm infection model. The SA1684 gene product carried the DUF402 domain, which is found in RNA-binding proteins, and had amino acid sequence similarity with a nucleoside diphosphatase, Streptomyces coelicolor SC4828 protein. The SA1684-deletion mutant exhibited drastically decreased virulence, in which the LD50 against silkworms was more than 10 times that of the parent strain. The SA1684-deletion mutant also exhibited decreased exotoxin production and colony-spreading ability. Purified SA1684 protein had Mn(2+)- or Co(2+)-dependent hydrolyzing activity against nucleoside diphosphates. Alanine substitutions of Tyr-88, Asp-106, and Asp-123/Glu-124, which are conserved between SA1684 and SC4828, diminished the nucleoside diphosphatase activity. Introduction of the wild-type SA1684 gene restored the hemolysin production of the SA1684-deletion mutant, whereas none of the alanine-substituted SA1684 mutant genes restored the hemolysin production. RNA sequence analysis revealed that SA1684 is required for the expression of the virulence regulatory genes agr, sarZ, and sarX, as well as metabolic genes involved in glycolysis and fermentation pathways. These findings suggest that the novel nucleoside diphosphatase SA1684 links metabolic pathways and virulence gene expression and plays an important role in S. aureus virulence., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

High blood pressure in middle age (up to 64 years) has been proposed as a predictive indicator of dementia. However, the association between hypertension and the cognitive functioning is controversial in older age groups. The aim of this study was to investigate this association in 70-80-year-old participants in the Japanese study of Septuagenarians, Octogenarians and Nonagenarians Investigation with Centenarians (SONIC). Participants aged 70 (±1) and 80 (±1) years (n=1000 and 973, respectively) were randomly recruited from the general population in Japan. Cognitive functioning was measured by the Montreal Cognitive Assessment. Blood pressure and other medical and social variables were analyzed by multiple regression analyses. High systolic blood pressure (SBP) was significantly correlated with a reduced cognitive functioning only in participants aged 70 years. Additionally, this correlation became more marked in participants with uncontrolled blood pressure at age 70 years. In contrast, SBP was not significantly correlated with the cognitive functioning at age 80 years. Nutritional status indicators such as serum albumin and frequency of going outdoors were significantly associated with cognitive functioning at age 80 years. Our findings indicate that high SBP has a significant role in cognitive functioning at age 70 years; however, blood pressure is less important as a risk factor for cognitive decline at age 80 years.

We previously reported that the rRNA methyltransferases RsmI and RsmH, which are responsible for cytidine dimethylation at position 1402 of 16S rRNA in the decoding center of the ribosome, contribute to Staphylococcus aureus virulence. Here we evaluated other 16S rRNA methyltransferases, including KsgA (RsmA), RsmB/F, RsmC, RsmD, RsmE, and RsmG. Knockout of KsgA, which methylates two adjacent adenosines at positions 1518 and 1519 of 16S rRNA in the intersubunit bridge of the ribosome, attenuated the S. aureus killing ability against silkworms. The ksgA knockout strain was sensitive to oxidative stress and had a lower survival rate in murine macrophages than the parent strain. The ksgA knockout strain exhibited decreased translational fidelity in oxidative stress conditions. Administration of N-acetyl-l-cysteine, a free-radical scavenger, restored the killing ability of the ksgA knockout strain against silkworms. These findings suggest that the methyl-modifications of 16S rRNA by KsgA contribute to maintain ribosome function under oxidative conditions and thus to S. aureus virulence., (Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)