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Abstract. Time perspectives may change as people age and become more aware of their limited time remaining in life. A research question is whether awareness of one’s limited time remaining associates with pet ownership among older adults. Although owning pets in old age involves both benefits and risks, the association between pet ownership and subjective remaining time in life remains understudied. The present study examines the associations between pet ownership and the subjective perception of time remaining in life among older adults. We assessed the experience of pet ownership (dog or cat) and age-related future time perspectives of 329 community-dwelling older adults in Japan. By adopting three constructs of the Future Time Perspective scale, we found that current dog ownership was associated with more limited future opportunities but not with limited time left or future constraints. Older dog owners may focus on the present rather than new future opportunities, yet they may see the future of their dogs that require care. Yet no such association was observed among current cat owners. The present findings extend the previous research of age-related future time perspectives by suggesting that pet ownership in late adulthood may be another contributing factor that needs to be better understood.

This is a review article based on the international symposium report of the "US-Japan Conference on Advances in Oncology: Cancer and Infectious Diseases" held online on June 25, 2021, which provided an update on the association between oncology and infectious disease research from cutting-edge basic science to high-impact clinical trials.

A dearth of evidence remains regarding the acceptance of care technologies by middle-aged adults that will need long-term care in the future. Therefore, we identified the factors associated with the acceptance of care technologies for bathing among middle-aged adults in Japan. Of the 1937 participants, 1553 participants were willing to receive bathing assistance from care technologies. The factors positively related to the acceptance of care technologies were female sex and higher educational levels.

A dearth of evidence remains regarding the acceptance of care technologies by middle-aged adults that will need long-term care in the future. Therefore, we identified the factors associated with the acceptance of care technologies for bathing among middle-aged adults in Japan. Of the 1937 participants, 1553 participants were willing to receive bathing assistance from care technologies. The factors positively related to the acceptance of care technologies were female sex and higher educational levels.

Periodontitis is a prevalent human disease of inflammation-induced bone destruction. Through studies in patient lesions of rare and common forms of periodontitis and animal model experimentation, Th17/IL-17 related immune pathways have emerged as mediators of disease pathology. In this focused review, we examine mechanisms of induction, amplification and pathogenicity of Th17 cells in periodontitis.

Identity and integrity (i.e., a sense of coherence and wholeness) are important elements for psychosocial development in later stages of life as described in Erikson’s life-span developmental theory. This study aimed to develop an intervention program to increase the sense of identity and integrity among older adults. The program included two types of workshops to examine the combined impact of searching for one’s post-retirement identity and clarifying personal goals and purpose for later life. The first workshop, Introductory of Active Aging, focused on providing the knowledge and skills necessary to prepare for life after retirement. The second workshop, Creating Your Life History, focused on a life review and composing one’s life history using the guided autobiography method developed by Birren. The study used a crossover design with a one-week break interval between the two workshops. Each workshop was conducted weekly with a two-hour session over four weeks. Thirty-eight participants aged 60 to 80 attended both workshops between October and December 2021 at a community center in Tokyo, Japan. The sense of identity and integrity were assessed using the Japanese version of the Erikson Psychosocial Inventory Scale (EPSI) at baseline and after completing both workshops (9th week). The scores of both identity and integrity increased significantly among participants who completed two workshops in sequence. This crossover study showed no statistical difference in the effects of each workshop. Further work is needed to monitor the long-term impact of these workshops in clarifying one’s identity and achieving satisfaction with self in later life.

Dental enamel, the hardest tissue in the human body, is derived from dental epithelial cell ameloblast-secreted enamel matrices. Enamel mineralization occurs in a strictly synchronized manner along with ameloblast maturation in association with ion transport and pH balance, and any disruption of these processes results in enamel hypomineralization. G protein–coupled receptors (GPCRs) function as transducers of external signals by activating associated G proteins and regulate cellular physiology. Tissue-specific GPCRs play important roles in organ development, although their activities in tooth development remain poorly understood. The present results show that the adhesion GPCR Gpr115 (Adgrf4) is highly and preferentially expressed in mature ameloblasts and plays a crucial role during enamel mineralization. To investigate the in vivo function of Gpr115, knockout (Gpr115-KO) mice were created and found to develop hypomineralized enamel, with a larger acidic area because of the dysregulation of ion composition. Transcriptomic analysis also revealed that deletion of Gpr115 disrupted pH homeostasis and ion transport processes in enamel formation. In addition, in vitro analyses using the dental epithelial cell line cervical loop–derived dental epithelial (CLDE) cell demonstrated that Gpr115 is indispensable for the expression of carbonic anhydrase 6 (Car6), which has a critical role in enamel mineralization. Furthermore, an acidic condition induced Car6 expression under the regulation of Gpr115 in CLDE cells. Thus, we concluded that Gpr115 plays an important role in enamel mineralization via regulation of Car6 expression in ameloblasts. The present findings indicate a novel function of Gpr115 in ectodermal organ development and clarify the molecular mechanism of enamel formation.

Subjective age (i.e., how old one feels) has been found to be a biopsychosocial marker of aging. This study examined the associations between subjective age and the frequency of information and communication technology (ICT) usage by older adults. Data were collected via an online survey conducted in 2020 during the COVID-19 pandemic. The study analyzed responses from participants aged 65 to 89 (M = 71.9, SD = 3.9) who resided in Japan (N = 1631, 52.8% female). Subjective age was indexed by asking participants to specify in years how old they felt. Proportional discrepancy scores (PDS) were calculated to indicate younger or older subjective age and were used as an independent variable. Participants were asked about the frequency of computer, smartphone, flip phone, tablet, and social networking service (SNS) use. Two-thirds of the participants (63.6%) reported feeling younger than their actual age. Nearly 90% reported using computers for more than 2–3 days a week, while 64.3% reported smartphone use, 22.9% reported flip phone use, and 36.6% reported SNS use. Logistic regression analyses revealed that a lower PDS (i.e., feeling younger) was associated with a significantly higher frequency of smartphone use (OR: 0.77; 95% CI: 0.60, 0.98) after adjusting for potential confounders. No such association was found for computer, flip phone, tablet, or SNS use. Our study found that feeling younger was associated with a higher frequency of smartphone use. The daily use of smartphones may have helped older adults stay in touch with family and friends and obtain the information that they needed, which may have contributed to better psychological well-being outcomes, especially during the COVID-19 pandemic.

In 2000, Japan introduced a mandatory long-term care insurance program to facilitate aging-in-place of older care recipients; there has been a great demand for assistive technologies such as AI (artificial intelligence) and robots in care settings to reduce the burden of caregivers and long-term care costs in society. This study examined the relationship between the trust in social security and acceptance of assistive technology for ADL help and discussed the challenges in introducing technology in a well-developed social security system. An online survey was conducted in August 2020 among community-dwelling individuals aged between 40 and 89 across Japan to find out their acceptance of help provided via AI or robotics technology in five dimensions of ADL. In addition, a 5-point Likert scale was used to assess the trust in social security.A total of 4,047 respondents were analyzed in this study. The respondents’ mean age was 60.6 (SD=11.3), and 53.2% of them were female. Of those, 13.2% preferred help from humans in ADL, while for 86.8%, the use of some assistive technology was acceptable. Logistic regression revealed that the female and younger respondents and those who had better health and had completed higher education were more likely to accept AI or robotics technology in all/some ADL if they needed assistance; those with higher trust in social security, however, were less likely to accept technology (OR=.894; p=.011).The challenges in introducing assistive technology under a well-developed social security system will be discussed.

Background Subjective age (SA) (i.e., felt age) has been found to be a biopsychosocial marker of aging. This study examined the associations between SA and frequency of technology usage of older adults. Methods Data were collected via an online survey conducted in 2020. The study analyzed participants aged 65 to 89 (M = 71.9, SD = 3.91) years resided in Japan (N = 1855, 54.3% women). SA was indexed by asking participants to specify in years how old they felt. Proportional discrepancy scores (PDS) ((SA - chronological age) / chronological age) were calculated to indicate younger or older SAs and used as an independent variable. Participants were asked about the frequency of computer, smartphone, flip phone, and SNS use. Results Nearly 90% reported using computers for more than 2-3 days a week, 64.3% smartphones, 22.9% flip phones, and 36.6% SNS. Logistic regression analyses revealed that lower PDS (i.e., feeling younger) was associated with a significantly higher frequency of smartphone use (OR: 0.75; 95% CI: 0.59, 0.96) after adjusting for age, gender, education, and subjective health. No such association was found for computer, flip phone, and SNS use. Implications: Older adults who use smartphones daily may feel younger than those who do not. Since the present study was administered during the COVID-19 pandemic, the daily use of smartphones may have helped older adults stay in touch with friends and family members and obtain information they need. The use of smartphones possibly contributed to better mental health outcomes while practicing social distancing.

The shortage of human resources in Japan has become a serious social issue in nursing care services owing to the rapid increase in the demand and the declining working population. Although the use of intelligent technologies such as robots, AI, and IT is expected to offer solutions, little progress has been made in the introduction and extensive use of these technologies in nursing care services. In this study, we aimed to clarify the factors that increase the preference for technology use in nursing care services from the perspective of trust. We conducted an online survey on attitudes towards nursing care and technologies in Japan, and statistically analyzed the relationships among the preference for technology use in nursing care, trust in technologies, and personal characteristics. The results revealed that those with high trust in intelligent technologies were more likely to prefer the use of such technologies in nursing care services.

Aim Cognitive decline increases mortality risk through dementia-related pathways and might be associated with increased healthcare costs. Using up to 12 years of repeated measures data, we identified trajectories in cognitive function among community-dwelling older Japanese adults. We then examined whether these trajectories were associated with all-cause and cause-specific mortality, and differences in healthcare costs. Methods A total of 1736 adults aged ≥65 years who were free of disabling dementia completed annual assessments during 2002-2014. Cognitive function was assessed with the Mini-Mental State Examination. The average number of follow-up assessments was 3.9, and the total number of observations was 6824 during the follow-up period. Results We identified five trajectory patterns in cognitive function (high, second, third, fourth, and low) during the 12-year follow-up period. The low (2.0%) and fourth (2.2%) trajectory groups had higher hazard ratios for cardiovascular disease mortality, and hazard ratios for other cause mortality were significantly higher for the third (16.8%) and second (38.8%) trajectory groups than for the high trajectory group (40.3%). Until 5 years of follow up, participants in the two lower-trajectory groups had higher mean combined monthly medical and long-term care costs. After 8 years of follow up, mean costs were highest for the third trajectory. Conclusions The risk of death from cardiovascular disease was higher in the two lower-trajectory groups in cognitive function, and they showed higher healthcare costs during the first 5 years of follow up. After 8 years of follow up, the third trajectory had the highest healthcare costs, perhaps because of hospitalizations attributable to gradual cognitive decline. Geriatr Gerontol Int 2019; 19: 1236-1242.

Background Although meals that combine a staple food, main dish, and side dish (balanced meals) are recommended in Japan, the health effects of such meals are unclear. We investigated the association of frequency of eating balanced meals with frailty among community-dwelling older Japanese. Methods We analyzed data from 912 persons aged 65 years or older who participated in the Hatoyama Cohort Study or Kusatsu Longitudinal Study. The frequency of eating two or more balanced meals daily was self-reported as ≤1 day/week, 2 or 3 days/week, 4 or 5 days/week, and daily. Frailty was defined as the presence of at least three, and pre-frailty as the presence of one or two, of the following criteria: weight loss, muscle weakness, exhaustion, slowness, and low physical activity. Adjusted logistic regression was used to study associations of frequency of balanced-meal consumption with frailty (prefrailty and frailty combined) and frailty criteria. Results Participants reporting a frequency of balanced-meal consumption of ≤2 or 3 days/week had a higher prevalence of frailty (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.21-2.64) than did those reporting a frequency of daily. Lower frequency of balanced-meal consumption was also associated with higher prevalences of weight loss (OR, 4.10; 95% CI, 1.90-8.85), exhaustion (OR, 6.35; 95% CI, 2.49-16.17), and low physical activity (OR, 1.92; 95% CI, 1.22-3.01). Conclusions Our findings suggest that more frequent twice daily consumption of meals with a staple food, main dish, and side dish decreases the risks of prefrailty and frailty.

Glioblastoma (GBM) is pathologically characterized by highly malignant neoplastic cells, focal necrosis and aberrant blood vessels composed of disorganized endothelial cells and pericytes. The recent cancer microarray database revealed upregulation of fibulin-7 (Fbln7), a member of the fibulin family, but provided no information on the tissue localization or biological function. In the present study, we demonstrated that Fbln7 is markedly overexpressed by the GBM tissue among astrocytic tumors, and immunolocalized mainly to endothelial cells and pericytes of the glomeruloid and hypertrophied microvessels. The production of Fbln7 by endothelial cells and pericytes was confirmed in cultured human umbilical vein endothelial cells (HUVEC) and human brain vascular pericytes (HBVP) and vascular endothelial growth factor (VEGF) stimulated the Fbln7 expression in HUVEC. Fbln7 bound to angiopoietin-1, but not angiopoietin-2 or Tie2 receptor, through interaction between the N-terminal portions of Fbln7 and angiopoietin-1, and it blocked phosphorylation of Tie2 receptor in HUVEC. In a coculture assay using HUVEC and HBVP, multilayered and irregular-shaped tube-like structures of HUVEC were induced by treatment with a high concentration of VEGF. This was accompanied by Fbln7 overproduction by HUVEC and angiopoietin-1 expression by HBVP. The production of aberrant VEGF-induced tube-like structures was attenuated by treatment with antibody or synthetic peptides specific to the Fbln7 N-terminal domain or knockdown of Fbln7. These data demonstrate that Fbln7 is overexpressed by endothelial cells and pericytes of the abnormal microvessels in GBM, and suggest that Fbln7 may contribute to the aberrant vessel formation by modulation of the angiopoietin-1/angiopoietin-2-Tie2 axis.

Background Preventing and reducing frailty is an important challenge for Japan in the next decade, especially in metropolitan areas. We launched a community-wide intervention trial (the Ota Genki Senior Project) in 2016 to develop effective community-based strategies for frailty prevention in metropolitan areas. This report describes the study design and baseline survey. Methods This study is a community-wide intervention trial that integrates participatory action research into a cluster non-randomized controlled trial for adults aged 65 years or older living in Ota City, Tokyo. We allocated 3 of 18 districts to an intervention group and the other 15 to a control group. Using a mailed self-administered questionnaire, we conducted a baseline survey of 15,500 residents (8,000 and 7,500 in the intervention and control groups, respectively) from July through August 2016. In addition to socioeconomic status and lifestyle variables, we assessed frailty status (primary outcome) and physical, nutritional, and psychosocial variables (secondary outcomes). Based on the baseline findings, an intervention to improve outcomes will be implemented as participatory action research. Follow-up surveys will be conducted in the same manner as the baseline survey. Results A total of 11,925 questionnaires were returned (76.9% response rate; 6,105 [76.3%] and 5,820 [77.6%] in the intervention and control groups, respectively), and 11,701 were included in the analysis (mean age, 74.3 [standard deviation, 5.5] years; 48.5% were men). Conclusions This study is expected to contribute to development of a prototype of a community-wide frailty prevention strategy, especially in metropolitan areas in Japan. Trial registration UMIN Clinical Trials Registry (UMIN000026515).

Background: Serum albumin and hemoglobin levels are independently associated with subsequent cognitive deterioration in older adults. This prospective study used repeated measures analysis to identify aging trajectories in serum albumin and hemoglobin levels and investigated if these trajectories were associated with incident disabling dementia among community-dwelling older Japanese. Methods: A total of 2,005 adults aged 65–90 years participated in annual geriatric health assessments during the period from June 2002 through July 2017; the total number of observations was 9,330. A review of a municipal database of the Japanese public long-term care insurance system identified 1,999 of 2,005 adults without dementia at baseline, 278 (13.9%) of whom developed disabling dementia during the follow-up period (June 2002 through December 2017). Results: We identified three trajectory patterns (high, moderate, and low) for serum albumin and hemoglobin levels for the age period 65 through 90 years. After controlling for potential confounders, participants with moderate and low trajectories for serum albumin level had hazard ratios of 1.27 (95% confidence interval 0.94–1.72) and 2.07 (1.37–3.11), respectively, for the development of incident disabling dementia, with the high trajectory group as reference. The respective hazard ratios for hemoglobin level were 1.31 (0.93–1.85) and 1.58 (1.04–2.40), respectively. Conclusion: Dementia risk was higher for individuals with low trajectories for serum albumin and hemoglobin levels. This finding highlights the importance of interventions that improve nutritional status and control relevant diseases in middle-aged and older adults with low serum albumin and hemoglobin levels.

Simple Summary The COVID-19 pandemic may have accelerated social isolation, particularly of older adults who are at increased risk of severe illness, while practicing physical distancing and self-quarantine. This study conducted in a metropolitan area of Japan hopes to provide stronger cross-cultural evidence of the positive impact of pet ownership on the psychological health of socially isolated owners with its large sample of older adults comparing two types of pet ownership (i.e., dog or cat). In this study, experience of dog or cat ownership and the presence or absence of social isolation were categorized into four groups to compare psychological health of each group. After adjusting for demographic and potential confounders, we found that socially isolated older adults who never owned a dog were more likely to report lower psychological health in comparison to socially isolated current or past dog owners. Our findings have practical implications that pets, particularly dogs, can play a role in increasing opportunities for engaging in physical and social activities and providing emotional support and thereby reducing a sense of social isolation and loneliness and improving psychological health among older adults. Abstract The psychological health effects of pet ownership have been widely studied, but only a few studies investigated its impact among socially isolated older adults. The present study aims to investigate the psychological health of older adults with or without the experience of pet (i.e., dog or cat) ownership who are socially isolated or not socially isolated. This study used cross-sectional data from 9856 community-dwelling older adults in a metropolitan area of Japan. Social and non-social isolation and type of pet ownership (i.e., dog or cat) were stratified to examine the psychological health. Logistic regression models indicated that, after adjusting for demographic and potential confounders, socially isolated older adults who never owned a dog were 1.22 times more likely to report lower psychological health in comparison to socially isolated current or past dog owners. No such difference was observed among cat owners. The results suggest that the experience of dog ownership may be effective to improve the psychological health among socially isolated older adult.

Aim Using up to 13 years of repeated-measures data, we identified aging trajectories for an index in frailty score among older Japanese undergoing health checkups. In addition, we examined whether these trajectories were associated with all-cause and cause-specific mortality and healthcare costs. Methods In total, 1698 adults aged ≥65 years completed annual assessments during 2002-2014. During follow-up, the average number of follow-up assessments was 3.9, and the total number of observations was 6373. Frailty was defined by using the following criteria from Fried's phenotype: slowness, weakness, exhaustion, low physical activity and weight loss. Results We identified four aging trajectories for frailty. Specifically, 6.5%, 47.3%, 30.3% and 16.0% of participants were in the high, second, third and low trajectory groups, respectively. As compared with the low trajectory group, the high trajectory group had greater risks of cardiovascular disease (adjusted hazard ratios of 3.42) and other-cause death (adjusted hazard ratios of 3.04). The high trajectory group had the highest medical costs until late in the eighth decade of life, costs decreased after age 70 years and were lowest at age 90 years (estimated at $116.7); however, medical and long-term care costs greatly increased after age 80 years in the second and third trajectory groups. Conclusions Higher aging trajectories in frailty score were associated with elevated risks for cardiovascular, other-cause and all-cause death among older Japanese receiving health checkups. Medical and care needs greatly increased for the second and third trajectory groups when their frailty level was progressed in later life. Geriatr Gerontol Int 2020; 20: 1072-1078..

Sjögren’s syndrome (SS) is a systemic autoimmune disease that mainly affects exocrine salivary and lacrimal glands. Local inflammation in the glands is thought to trigger glandular dysfunction and symptoms of dryness. However, the mechanisms underlying these processes are incompletely understood. Our work suggests T cell exosome–derived miR-142-3p as a pathogenic driver of immunopathology in SS. We first document miR-142-3p expression in the salivary glands of patients with SS, both in epithelial gland cells and within T cells of the inflammatory infiltrate, but not in healthy volunteers. Next, we show that activated T cells secreted exosomes containing miR-142-3p, which transferred into glandular cells. Finally, we uncover a functional role of miR-142-3p–containing exosomes in glandular cell dysfunction. We find that miR-142-3p targets key elements of intracellular Ca(2+) signaling and cAMP production — sarco(endo)plasmic reticulum Ca(2+) ATPase 2b (SERCA2B), ryanodine receptor 2 (RyR2), and adenylate cyclase 9 (AC9) — leading to restricted cAMP production, altered calcium signaling, and decreased protein production from salivary gland cells. Our work provides evidence for a functional role of the miR-142-3p in SS pathogenesis and promotes the concept that T cell activation may directly impair epithelial cell function through secretion of miRNA-containing exosomes.

Accumulating evidence from studies of human–animal interaction highlights the physiological, psychological, and social benefits for older owners of dogs and cats. This longitudinal study examined whether experience of dog/cat ownership protects against incident frailty in a population of community-dwelling older Japanese. Among 7881 non-frail community-dwelling adults aged 65 years or older who completed a mail survey in 2016, 6,197 (mean [SD] age, 73.6 [5.3] years; 53.6% women) were reevaluated in a 2018 follow-up survey. Frailty was assessed with the Kaigo-Yobo Checklist. Incident frailty was defined as a score of four or higher in the follow-up survey. Overall, 870 (14.0%) were current dog/cat owners, 1878 (30.3%) were past owners and 3449 (55.7%) were never owners. During the 2-year follow-up period, 918 (14.8%) developed incident frailty. Mixed-effects logistic regression models showed that the odds ratio for incident frailty among dog/cat owners, as compared with never owners, current owners were 0.87 (95% confidence interval [CI]: 0.69–1.09) and past owner were 0.84 (0.71–0.98), after controlling for important confounders at baseline. In stratified analysis, the risk of incident frailty was lower for past dog owners than for cat owners. Longer experience of caring for a dog requires physical activity and increases time outdoors spent dog walking and thus may have an important role in maintaining physical and social function and reducing frailty risk among older adults.

Long-term care facilities for older adults have been profoundly affected by the coronavirus disease 2019 (COVID-19) pandemic in Japan. This study investigated the challenges that care staff members faced by the height of the first wave (i.e., April 2020) and the height of the second wave (i.e., October 2020) of the pandemic at long-term care facilities in Japan. We mailed questionnaires in October 2020 to 5,895 care facilities throughout Japan. A total of 22.7% of the questionnaires were returned. Of those, 87.4% had at least one resident with dementia. Based on the results, 65.2% reported having restricted all visitors during the first wave. Although 42.8% reported continuing to restrict all visitors during the second wave, more than 54% allowed visitors while limiting the number of visitors or the time of each visit. Nearly 76% reported that restrictions on visitations may have exacerbated the behavioral and psychological symptoms of dementia (BPSD) among residents. In place of visitations, over 50% used video calls or phone calls to communicate with the family members, and 45.7% reported that the virtual visits were efficacious in alleviating the BPSD. However, more than 70% reported not having adequate Internet services and computer equipment at their facilities, and nearly 90% reported insufficient staffing. Our findings suggest that the pandemic may have pressed for a change of direction for dementia care with the introduction of virtual visitations and other initiatives. Nevertheless, facilities may face difficulties with implementing such changes due to inadequacies in the availability of resources.

Background Various technologies to provide long-term care have been developed in the last decade due to the shortage of caregivers in Japan. However, care technologies are not widely used in long-term care, and the reasons for the lack of acceptance of care technologies are poorly understood. Objectives To identify the factors associated with the acceptance of care technologies designed to assist with activities of daily living (i.e., bathing, dressing, toileting, transferring, and eating) among middle-aged and older adults in Japan. Design and Methods A cross-sectional survey was conducted in August 2020. The target population was middle-aged and older adults (i.e., 40–79 years) in Japan. We used an online questionnaire platform of a research company to target people throughout Japan, and measured the acceptance of care technologies to support the performance of each of five activities of daily living. Multivariable logistic regression models were fitted to identify the associated factors using the bivariate variable “willingness to use care technologies for activities of daily living” as the dependent variable. Results A total of 3261 eligible respondents were included in the analysis. The factors positively associated with the acceptance of care technologies for transferring, which had the highest level of acceptance, were female sex (adjusted odds ratio=1.25, 95% CI: 1.04–1.52), university or higher education level (1.73, 1.41–2.12), an annual income of 39000 to 58999 USD (1.47, 1.08–2.01) or greater than 99,000 USD (1.88, 1.21–2.94), experience as an informal caregiver (1.25, 1.02–1.54), the use of social networking services a few times per year (1.40, 1.11–1.78) or nearly every day (1.47, 1.19–1.82), and willingness to live in a nursing home when care is needed (1.29, 1.05–1.60). In contrast, aged 70–79 years was negatively associated with the acceptance of care technologies for transferring (0.70, 0.52–0.93). Conclusion Female sex, university or higher education level, an annual income greater than 99,000 USD, the use of social networking services a few times per year or more often, and willingness to live in a nursing home when care is needed were positively associated with the acceptance of care technologies for multiple activities of daily living. Given that many of the respondents will need care in 5–10 years, the acceptance of care technologies among those who need care will increase. Therefore, governments and developers of care technologies could consider the potential needs of this population group.

Purpose Finger sucking is the most commonly observed habit in children. However, a prolonged sucking habit may have negative effects on dentition and occlusal development, including maxillary protrusion, anterior open bite, and posterior cross-bite. For treatment of malocclusion, early detection is important, especially in children, though it is difficult to exam oral habits using typical dental examination methods. In this study, we report the relationship between a callus on the sucking finger and malocclusion. Methods While performing dental examinations, we checked the fingers of 719 children (0–6 years old) who were attending 10 different kindergartens in Sendai City, Japan, in 2009 to determine the presence of a sucking callus formed by a finger sucking habit. Results The peak ratios of children with a sucking callus and malocclusion was at the age of 2 years (13.6% and 11.0%, respectively), and then decreased with age. Maxillary protrusion was detected in 42.9%, 56.2%, 42.9%, and 37.5% of the children with a sucking callus at the age of 1, 2, 3, and 4 years old, respectively. In those with maxillary protrusion, a sucking callus was detected in 42.9%, 75%, 75%, and 60%, respectively. Conclusion We concluded that the presence of a sucking callus is a useful indicator for malocclusion caused by an oral habit.

Objectives We examined the dose-response relationships of body composition indices with mortality and identified the best predictor. Design and setting Kusatsu Longitudinal Study and Hatoyama Cohort Study, Japan. Participants In total, 1977 community-dwelling Japanese adults age ≥65 years (966 men and 1011 women) participated. Measurements Body mass index (BMI), fat mass index (FMI), fat-free mass index (FFMI), and skeletal muscle mass index (SMI) were determined by segmental multifrequency bioelectrical impedance analysis. The main outcome was all-cause mortality. We determined multivariate-adjusted hazard ratios for mortality relative to sex-specific medians of each body composition index and examined the association shapes. Results During the median follow-up of 5.3 years, 128 (13.3%) men and 75 (7.4%) women died. Compared with median BMIs (23.3 kg/m2 in men and 22.8 kg/m2 in women), a BMI >23.3 and ≤26.1 kg/m2 was associated with significantly lower mortality risk in men, and a BMI Conclusions and Implications FFMI and SMI were more definitive predictors of mortality than were BMI and FMI. The lower mortality risk with higher FFMI, regardless of FMI, may explain the age-related weakening of the association between higher BMI and mortality (the “obesity paradox”). FFMI and SMI evaluation should be introduced to clinical assessments of older adults because mortality risk might be reduced by maintaining muscle mass.

Angiogenesis is crucial for tissue development and homeostasis; however, excessive angiogenesis can lead to diseases, including arthritis and cancer metastasis. Some antiangiogenic drugs are available, but side effects remain problematic. Thus, alternative angiogenesis inhibition strategies are needed. Fibulin-7 (Fbln7) is a newly discovered member of the fibulin protein family, a group of cell-secreted glycoproteins, that functions as a cell adhesion molecule and interacts with other extracellular matrix (ECM) proteins as well as cell receptors. We previously showed that a recombinant C-terminal Fbln7 fragment (Fbln7-C) inhibits tube formation by human umbilical vein endothelial cells (HUVECs) in vitro. In the present study, we examined the in vivo antiangiogenic activity of recombinant full-length Fbln7 (Fbln7-FL) and Fbln7-C proteins using a rat corneal angiogenesis model. We found that both Fbln7-FL and Fbln7-C inhibited neovascularization. Fbln7-C bound to vascular endothelial growth factor receptor 2 (VEGFR2), inhibiting VEGFR2 and ERK phosphorylation and resulting in reduced HUVEC motility. HUVEC attachment to Fbln7-C occurred through an interaction with integrin α5β1 and regulated changes in cellular morphology. These results suggest that Fbln7-C action may target neovascularization by altering cell/ECM associations. Therefore, Fbln7-C could have potential as a therapeutic agent for diseases associated with angiogenesis.

As of 2015, there is only one master's program of gerontology acknowledged by each of the following countries: Japan, Taiwan, and Turkey. All three programs have fewer than 15 years of history. These three countries differ in society types based on the proportion of older adults, rate of population aging, and population size. However, in terms of gerontological education, they seem to share great commonalities. Common challenges are a lack of awareness of the field of gerontology, insufficient numbers of gerontology programs and faculty members to produce trained gerontologists within society, and the inadequacy of opportunities for trained gerontologists to play an active role in various fields. This study intends not only to compare the differences and similarities among three countries and programs, but also to elucidate characteristics of a unique gerontology program in each country and identify challenges and possibilities from the perspective of gerontological educators.

Despite the research done on pathological angiogenesis, there is still a need for the development of new therapies against angiogenesis-related diseases. Fibulin-7 (Fbln7) is a member of the extracellular matrix fibulin protein family. The Fbln7 C-terminal fragment, Fbln7-C, binds to endothelial cells and inhibits their tube formation in culture. In this study, we screened 12 synthetic peptides, covering the fibulin-globular domain of Fbln7-C, to identify active sites for endothelial cell adhesion and in vitro antiangiogenic activity. Three peptides, fc10, fc11, and fc12, promoted Human Umbilical Vein Endothelial Cells (HUVECs) adhesion, and the morphology of HUVECs on fc10 was similar to that on Fbln7-C. EDTA and the anti-integrin β1 function-blocking antibody inhibited HUVECs adhesion to both fc10 and fc12, and heparin inhibited HUVECs adhesion to both fc11 and fc12. fc10 and fc11 inhibited HUVECs tube formation. Our results suggest that three peptides from Fbln7-C are biologically active for endothelial cell adhesion and disrupt the tube formation, suggesting a potential therapeutic use of these peptides for angiogenesis-related diseases. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 184-195, 2016.

Wet age-related macular degeneration (AMD) and diabetic retinopathy are the leading causes of blindness through increased angiogenesis. Although VEGF-neutralizing proteins provide benefit, inconsistent responses indicate a need for new therapies. We previously identified the Fibulin-7 C-terminal fragment (Fbln7-C) as an angiogenesis inhibitor in vitro. Here we show that Fbln7-C inhibits neovascularization in vivo, in both a model of wet AMD involving choroidal neovascularization (CNV) and diabetic retinopathy involving oxygen-induced ischemic retinopathy. Furthermore, a short peptide sequence from Fbln7-C is responsible for the anti-angiogenic properties of Fbln7-C. Our work suggests Fbln7-C as a therapeutic candidate for wet AMD and ischemic retinopathy.

Objectives To determine whether physical activity mediates the association of gait speed with incident disability and mortality in older adults. Study design Prospective cohort data from 782 community-dwelling Japanese older adults were analyzed. The median follow-up periods for incident disability and mortality were 4.4 and 4.5 years, respectively. Main outcome measures Physical activity was assessed with the Japan Arteriosclerosis Longitudinal Study Physical Activity Questionnaire, gait speed was calculated from 5-m walking time, and incident disability was defined as long-term care insurance certification during follow-up. Results There were 247 cases of incident disability and 202 deaths during follow-up. After adjusting for potential confounders, faster gait speed was associated with decreased risk of incident disability (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.82–0.93), but physical activity level was not associated with incident disability (HR = 0.98, 95% CI = 0.95–1.01). Gait speed was associated with mortality risk in the model without physical activity (HR = 0.93, 95% CI = 0.88–1.00). When gait speed and physical activity were both included in the model, gait speed was not associated with mortality (HR = 0.95, 95% CI = 0.89–1.02) but physical activity was associated with mortality (HR = 0.95, 95% CI = 0.92–0.99). Physical activity was a mediating factor in the association between gait speed and mortality (Sobel test p = .025). Conclusions Gait speed is directly associated with incident disability and is indirectly related to mortality through physical activity in older adults.

Periodontitis is one of the most common human inflammatory diseases, yet the mechanisms that drive immunopathology and could be therapeutically targeted are not well defined. Here, we demonstrate an expansion of resident memory T helper 17 (TH17) cells in human periodontitis. Phenocopying humans, TH17 cells expanded in murine experimental periodontitis through local proliferation. Unlike homeostatic oral TH17 cells, which accumulate in a commensal-independent and interleukin-6 (IL-6)-dependent manner, periodontitis-associated expansion of TH17 cells was dependent on the local dysbiotic microbiome and required both IL-6 and IL-23. TH17 cells and associated neutrophil accumulation were necessary for inflammatory tissue destruction in experimental periodontitis. Genetic or pharmacological inhibition of TH17 cell differentiation conferred protection from immunopathology. Studies in a unique patient population with a genetic defect in TH17 cell differentiation established human relevance for our murine experimental studies. In the oral cavity, human TH17 cell defects were associated with diminished periodontal inflammation and bone loss, despite increased prevalence of recurrent oral fungal infections. Our study highlights distinct functions of TH17 cells in oral immunity and inflammation and paves the way to a new targeted therapeutic approach for the treatment of periodontitis.

Fibulin-7 (Fbln7) has been identified as the latest member of the fibulin family of secreted glycoproteins in developing teeth, functioning as a cell adhesion molecule and interacting with other matrix proteins, receptors, and growth factors. More recently, we have shown that the C-terminal Fbln7 fragment (Fbln7-C) has antiangiogenic activity in vitro. Fbln7 is also expressed in immune-privileged tissues, such as eye and placenta, but its functional significance is unknown. In the current study, we show that human monocytes adhere to both full-length Fbln7 (Fbln7-FL) and Fbln7-C, in part, via integrins α(5)β(1) and α(2)β(1). Morphologic studies and surface expression analyses of CD14, mannose receptor (CD206), major histocompatibility complex II, and CD11b receptors revealed that both Fbln7-FL and Fbln7-C inhibit M-CSF–induced monocyte differentiation. Fbln7-C had significantly greater negative effects on cell spreading and stress fiber formation, including the production of IL-6 and metalloproteinase-1/-9 compared with Fbln7-FL. Furthermore, in an LPS-induced systemic inflammation model, Fbln7-C and Fbln7-FL reduced the infiltration of immune cells, such as neutrophils and macrophages, to the inflamed peritoneum. Thus, these results suggest that Fbln7 and Fbln7-C could modulate the activity of immune cells and have therapeutic potential for inflammatory diseases.—Sarangi, P. P., Chakraborty, P., Dash, S. P., Ikeuchi, T., de Vega, S., Ambatipudi, K., Wahl, L., Yamada, Y. Cell adhesion protein fibulin-7 and its C-terminal fragment negatively regulate monocyte and macrophage migration and functions in vitro and in vivo.

Periodontitis is one of the most common human inflammatory diseases, yet the mechanisms that drive immunopathology and could be therapeutically targeted are not well defined. Here, we demonstrate an expansion of resident memory Th17 cells in human periodontitis. Phenocopying humans, Th17 cells expanded in murine experimental periodontitis through local proliferation. Unlike homeostatic oral Th17 cells, which accumulate in a commensal-independent and IL-6-dependent manner, periodontitis-associated expansion of Th17 cells was dependent upon the local dysbiotic microbiome and required both IL-6 and IL-23. Importantly, Th17 cells and associated neutrophil accumulation were necessary for inflammatory tissue destruction in experimental periodontitis. Genetic or pharmacological inhibition of Th17 cell differentiation conferred protection from immunopathology. Studies in a unique patient population with a genetic defect in Th17 cell differentiation established human relevance for our murine experimental studies. Indeed, in the oral cavity, human Th17 cell defects were associated with diminished periodontal inflammation and bone loss, despite increased prevalence of recurrent oral fungal infections. Our study highlights distinct functions of Th17 cells in oral immunity and inflammation and paves the way to a new targeted therapeutic approach for the treatment of periodontitis.

Introduction: The blood-brain barrier (BBB) breakdown occurs when the integrity of BBB components is lost as a consequence of ischemic stroke. Perlecan, a major heparan sulfate proteoglycan of basement membranes, is expressed by endothelial cells (ECs) and is adjacent to pericytes (PCs), suggesting supportive functions in the BBB. Recent studies highlight the importance of PCs in the process of repairing BBB functions, which are triggered by the upregulation of platelet-derived growth factor receptor β (PDGFRβ). We hypothesized that perlecan may play a protective role in BBB maintenance through the interaction with PCs during the repair process of the BBB disruption. Methods: We induced a 60-minute middle cerebral artery occlusion (MCAO) in adult conditional perlecan -deficient ( Perlecan -/- -Tg) mice in a C57BL/6 background, which express the perlecan transgene only in cartilage to rescue the perinatal lethality of Perlecan -/- mice. Recombinant perlecan C-terminal domain V (DV) was used for in vitro assays. Results: Perlecan -/- -Tg mice exhibited larger infarct volumes and more BBB leakage than the control mice on post-surgery day (PSD) 2 after MCAO. While the control mice showed increased numbers of PDGFRβ-positive PCs around the ischemic lesion on PSD 3, such upregulation was not observed in Perlecan -/- -Tg mice, suggesting that perlecan may participate in PC activation against the BBB breakdown. In wild-type mice, the expression of integrin α5, a potential receptor for perlecan, was upregulated both in PCs and in ECs in the ischemic lesion. In culture, PCs showed attachment activity to DV through integrin α5β1. DV induced well-assembled actin stress fibers and focal adhesions in PCs and promoted the PC migration induced by PDGF-BB. At molecular level, DV enhanced the PDGF-BB-induced phosphorylation of PDGFRβ, in addition to that of SHP-2 and FAK, suggesting that DV enhanced both PDGFRβ and integrin signaling. Conclusions: These results revealed that perlecan regulates the activation of PCs through the cooperative function of PDGFRβ and integrin α5β1, contributing to the repair process of the BBB. Perlecan DV may provide a potential therapeutic effect, based on a new approach from extracellular matrix to the disrupted BBB in ischemic stroke.

Background: Subjective age (SA) has been found to be a biopsychosocial marker of aging, yet little is known about factors that influence SA development. This study examined factors influencing SA using longitudinal data of community-dwelling older Japanese. Methods: Data drawn from the Kusatsu Longitudinal Study were collected during annual health check-ups in 2017 and 2018 from participants (aged 65-95) who completed all the measurement items used for this analysis (N=981). SA was indexed by asking participants to specify in years how old they felt. Proportional discrepancy scores ((subjective age - chronological age)/chronological age ×100) were calculated to indicate younger or older SAs and used as a dependent variable. As influencing factors of SA, chronological age, sex, years of schooling, history of smoking, cognitive function (using MMSE scores, range 14-30 at baseline), depressive symptoms, physical function (gait speed), and social function (employment status) were examined. Analyses were performed with random-effects GLS regression models. Results: Significant partial regression coefficients were found for cognitive function (0.48%, CI: 0.18, 0.79), years of schooling (-0.42%, CI: -0.69, -0.15), depressive symptoms (0.32%, CI: 0.11, 0.53), and chronological age (-0.18%, CI: -0.30, -0.68). Implications: This study found that older age and longer years of schooling were associated with younger SA, while better cognition and depressive symptoms were linked to older SA. Better cognition being associated with older SA was inconsistent with existing studies. This may be due in part to the association of better cognition and the level of satisfaction influenced by awareness of age-related physical/social changes.

Objectives: Changes in age-related future time perspective (FTP) were found to influence people’s social network characteristics (SNC). Earlier studies revealed different patterns of adaptation to their personal network among older adults with or without nuclear family members. Using the framework of socioemotional selectivity theory (SST), this study examined the differential role of living arrangement in SNC between the cultures of Germany and Japan, which share many distinct characteristics, including the types of living arrangements among older adults.Methods: Our sample consisted of 139 German (71% live alone) and 136 Japanese (49% live alone) adults ranging in age from 60 to 90. The moderating role of living alone in the three way interactions of subjective health (SH), FTP, and SNC was tested.Results: Among Germans, more extended FTP was associated with an increasing number of very close social partners, when living alone and having rather poor or average health, as well as when living with someone and having rather better health. These findings were consistent with SST. However, no such associations were found among Japanese. Our additional analysis on the interaction between the effects of culture and living alone on FTP revealed a greater cultural effect in the live-alone situation than in the not-live-alone situation.Conclusions: Our study suggests that culture-specific associations between SH, FTP, and SNC may reflect differences of living arrangements between Germany and Japan. For example, living alone may have a stronger impact on the phenomenon of SST in Germany than in Japan.

Introduction: The disruption of the blood-brain barrier (BBB) is a contributing factor for the deterioration of brain damages in ischemic stroke. Recent studies revealed that microvascular pericytes are involved in the maintenance of the BBB and in the repair process through platelet-derived growth factor receptor β (PDGFRβ), the expression of which is increased around the ischemic lesion. Here we focus on perlecan, the major heparan sulfate proteoglycan in the basement membrane (BM). It is expressed by endothelial cells in the brain and is implicated in many biological functions. In this report, we have studied the role of Perlecan in the BBB breakdown and in the subsequent repair process after ischemic stroke in a mouse model. We hypothesized that perlecan may play a protective role in the disruption of BBB through the interaction with pericytes after ischemic stroke. Methods: To elucidate the role of perlecan in the brain vasculature, we induced a 60-minute transient middle cerebral artery occlusion (MCAO) in adult conditional perlecan -deficient ( Perlecan -/- -Tg) mice, which express the perlecan transgene only in the cartilage to rescue the perinatal lethality of perlecan -deficient mice. Results: Although the BBB formation and function in the brain vasculature appeared to be unaffected in Perlecan -/- -Tg mice under healthy condition, Perlecan -/- -Tg mice demonstrated larger infarct volumes and more BBB leakage than control mice on post-surgery day (PSD) 2 after MCAO. Perlecan -/- -Tg mice exhibited less PDGFRβ-positive pericytes around the ischemic lesion on PSD 3 to 7 than control mice, suggesting that the perlecan deficiency suppressed pericyte activation. At a mechanistic level, integrin α5, a potential receptor for perlecan, was detectable in both endothelial cells and pericytes in the ischemic lesion, suggesting that endothelial cell-derived perlecan may regulate pericyte activation in response to ischemia through integrin α5. Conclusions: Our results suggest that perlecan is required for the activation of pericytes and thereby, contributing to the endothelial cell-pericyte integrity in the BBB maintenance after ischemic stroke.