Dog, cat, bird, fish, and other pet ownership and mortality: Evidence from the HILDA cohort.

This study used the nationally representative prospective study of the Household, Income and Labour Dynamics in Australia (HILDA) survey cohort to examine the association of pet ownership (dog, cat, bird, fish, and others) with the risk of all-cause mortality using propensity score matching based on a wide range of factors. The study sample included 15,735 participants who completed the questionnaire on pet ownership in 2018. The HILDA survey sample was matched to the National Death Index through 2022 to assess death during the follow-up period. Statistical analysis was weighted by the inverse of the propensity score in the generalized estimating equation. During the 4-year follow-up period, 377 of 15,735 (2.4%) participants died. The odds ratios (ORs) for all-cause mortality were 0.77 (95%CI: 0.59-0.99) for dog owners compared to non-pet owners after controlling for related socio-demographic, physical, psychological, and social factors. The Sobel test showed a partial mediating effect of physical activity level on the relationship between dog ownership and all-cause mortality. Ownership of cats, birds, fish, and others showed no clear association with mortality, despite owners having similar socio-demographics characteristics to dog owners. Companionship and exercise of a pet dog may be recommended as a component of health promotion policy, and may have an important role to play in promoting health aging.

Transcription factor Tox2 is required for metabolic adaptation and tissue residency of ILC3 in the gut.

Group 3 innate lymphoid cells (ILC3) are the major subset of gut-resident ILC with essential roles in infections and tissue repair, but how they adapt to the gut environment to maintain tissue residency is unclear. We report that Tox2 is critical for gut ILC3 maintenance and function. Gut ILC3 highly expressed Tox2, and depletion of Tox2 markedly decreased ILC3 in gut but not at central sites, resulting in defective control of Citrobacter rodentium infection. Single-cell transcriptional profiling revealed decreased expression of Hexokinase-2 in Tox2-deficient gut ILC3. Consistent with the requirement for hexokinases in glycolysis, Tox2-/- ILC3 displayed decreased ability to utilize glycolysis for protein translation. Ectopic expression of Hexokinase-2 rescued Tox2-/- gut ILC3 defects. Hypoxia and interleukin (IL)-17A each induced Tox2 expression in ILC3, suggesting a mechanism by which ILC3 adjusts to fluctuating environments by programming glycolytic metabolism. Our results reveal the requirement for Tox2 to support the metabolic adaptation of ILC3 within the gastrointestinal tract.

Epithelial-derived interleukin-23 promotes oral mucosal immunopathology.

At mucosal surfaces, epithelial cells provide a structural barrier and an immune defense system. However, dysregulated epithelial responses can contribute to disease states. Here, we demonstrated that epithelial cell-intrinsic production of interleukin-23 (IL-23) triggers an inflammatory loop in the prevalent oral disease periodontitis. Epithelial IL-23 expression localized to areas proximal to the disease-associated microbiome and was evident in experimental models and patients with common and genetic forms of disease. Mechanistically, flagellated microbial species of the periodontitis microbiome triggered epithelial IL-23 induction in a TLR5 receptor-dependent manner. Therefore, unlike other Th17-driven diseases, non-hematopoietic-cell-derived IL-23 served as an initiator of pathogenic inflammation in periodontitis. Beyond periodontitis, analysis of publicly available datasets revealed the expression of epithelial IL-23 in settings of infection, malignancy, and autoimmunity, suggesting a broader role for epithelial-intrinsic IL-23 in human disease. Collectively, this work highlights an important role for the barrier epithelium in the induction of IL-23-mediated inflammation.

Dissociation of murine oral mucosal tissues for single cell applications.

Single-cell RNA sequencing and flow cytometry approaches have been instrumental in understanding cellular states within various tissues and organs. However, tissue dissociation methods can potentially alter results and create bias due to preferential recovery of particular cell types. Here we present efforts to optimize methods for dissociation of murine oral mucosal tissues and provide three different protocols that can be utilized to isolate major cell populations in the oral mucosa. These methods can be used both in health and in states of inflammation, such as periodontitis. The optimized protocols use different enzymatic approaches (collagenase II, collagenase IV and the Miltenyi whole skin dissociation kit) and yield preferential recovery of immune, stromal and epithelial cells, respectively. We suggest choosing the dissociation method based on the cell population of interest to study, while understanding the limitations of each approach.

Protective effects of dog ownership against the onset of disabling dementia in older community-dwelling Japanese: A longitudinal study.

This prospective study examined the associations of dog/cat ownership with incident disabling dementia using propensity score matching based on the physical, social, and psychological characteristics of dog and cat owners. We also examined associations of the interaction between dog/cat ownership and exercise habit and social isolation with dementia. Overall, 11,194 older adults selected using stratified and random sampling strategies in 2016 were analyzed. Dog/cat ownership was defined as "current" or "past and never". Disabling dementia was defined according to physicians' rating in the long-term care insurance system in Japan during the approximately 4-year follow-up period. Statistical analysis was weighted by the inverse of the propensity score in the generalized estimating equation after adjusting for follow-up period. Current dog owners (8.6 %) had an odds ratio (OR) of 0.60 (95 %CI: 0.37-0.977) of having disabling dementia compared to past and never owners. For cat ownership, the corresponding OR was 0.98 (95 %CI: 0.62-1.55). Current dog owners with a regular exercise habit had an OR of 0.37 (0.20-0.68) compared to past and never dog owners with no exercise habit. Further, current dog owners with no social isolation had an OR of 0.41 (0.23-0.73) compared to past and never dog owners with social isolation. Dog ownership had a suppressive effect on incident disabling dementia after adjusting for background factors over a 4-year follow-up period. Specifically, dog owners with an exercise habit and no social isolation had a significantly lower risk of disabling dementia.

Neutrophil extracellular traps and extracellular histones potentiate IL-17 inflammation in periodontitis.

Neutrophil infiltration is a hallmark of periodontitis, a prevalent oral inflammatory condition in which Th17-driven mucosal inflammation leads to destruction of tooth-supporting bone. Herein, we document that neutrophil extracellular traps (NETs) are early triggers of pathogenic inflammation in periodontitis. In an established animal model, we demonstrate that neutrophils infiltrate the gingival oral mucosa at early time points after disease induction and expel NETs to trigger mucosal inflammation and bone destruction in vivo. Investigating mechanisms by which NETs drive inflammatory bone loss, we find that extracellular histones, a major component of NETs, trigger upregulation of IL-17/Th17 responses, and bone destruction. Importantly, human findings corroborate our experimental work. We document significantly increased levels of NET complexes and extracellular histones bearing classic NET-associated posttranslational modifications, in blood and local lesions of severe periodontitis patients, in the absence of confounding disease. Our findings suggest a feed-forward loop in which NETs trigger IL-17 immunity to promote immunopathology in a prevalent human inflammatory disease.

Exploratory study on the factors related with the early detection of missing older persons with dementia living alone in Japan.

AIM: To clarify the factors related to the early detection of missing older persons with dementia (PwD) who lived alone in Japan. METHODS: We carried out a multiple regression analysis with data from 88 missing PwD. RESULTS: The location of the discovery was within the municipality where the missing PwD lived. Furthermore, the use of long-term care insurance services was significantly associated with early detection. CONCLUSION: Missing PwD were located within the municipality in which they lived, which meant that the individual was found before they went far. In addition, with the long-term care insurance services, professionals should regularly visit the home of PwD according to a care plan. Planned regular visits might trigger the early recognition of a missing person with dementia and enable early search activities. Therefore, use of long-term care insurance services might lead to the early detection of missing PwD living alone. Geriatr Gerontol Int 2023; 23: 362-365.

Deficiency of G protein-coupled receptor Gpr111/Adgrf2 causes enamel hypomineralization in mice by alteration of the expression of kallikrein-related peptidase 4 (Klk4) during pH cycling process.

Enamel is formed by the repetitive secretion of a tooth-specific extracellular matrix and its decomposition. Calcification of the enamel matrix via hydroxyapatite (HAP) maturation requires pH cycling to be tightly regulated through the neutralization of protons released during HAP synthesis. We found that Gpr115, which responds to changes in extracellular pH, plays an important role in enamel formation. Gpr115-deficient mice show partial enamel hypomineralization, suggesting that other pH-responsive molecules may be involved. In this study, we focused on the role of Gpr111/Adgrf2, a duplicate gene of Gpr115, in tooth development. Gpr111 was highly expressed in mature ameloblasts. Gpr111-KO mice showed enamel hypomineralization. Dysplasia of enamel rods and high carbon content seen in Gpr111-deficient mice suggested the presence of residual enamel matrices in enamel. Depletion of Gpr111 in dental epithelial cells induced the expression of ameloblast-specific protease, kallikrein-related peptidase 4 (Klk4), suggesting that Gpr111 may act as a suppressor of Klk4 expression. Moreover, reduction of extracellular pH to 6.8 suppressed the expression of Gpr111, while the converse increased Klk4 expression. Such induction of Klk4 was synergistically enhanced by Gpr111 knockdown, suggesting that proper enamel mineralization may be linked to the modulation of Klk4 expression by Gpr111. Furthermore, our in vitro suppression of Gpr111 and Gpr115 expression indicated that their suppressive effect on calcification was additive. These results suggest that both Gpr111 and Gpr115 respond to extracellular pH, contribute to the expression of proteolytic enzymes, and regulate the pH cycle, thereby playing important roles in enamel formation.

Does Smartphone Use Make Older Adults Feel Younger? A Cross-Sectional Online Survey during the COVID-19 Pandemic.

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.

Pet ownership-related differences in medical and long-term care costs among community-dwelling older Japanese.

This study examined the differences in medical and long-term care costs over 18 months between pet owners and non-owners among community-dwelling older Japanese. Pet ownership data were collected from 460 community-dwelling adults age 65 years and older. These data were matched with data from the National Health Insurance, health insurance for older people, and Long-Term Care Insurance beneficiaries for 17 months back from the survey on pet ownership. Pet-ownership group-specific trajectories in monthly medical and long-term care costs were modeled by a generalized estimating equation. Among pet owners (n = 96, 20.9%) and non-pet owners (n = 364, 79.1%) there were no significant differences in baseline demographic or health characteristics including chronic disease and self-reported long-term care level. At baseline, pet owners had estimated monthly medical costs of ¥48,054 (SE = 0.11; $418), compared to ¥42,260 (SE = 0.06; $367) for non-pet owners. The monthly medical costs did not differ significantly between the two groups during the 18-month follow-up period. At baseline, estimated monthly long-term care costs of pet owners and non-pet owners were ¥676 (SE = 0.75; $6) and ¥1,420 (SE = 0.52; $12), respectively. During the follow-up period, the non-pet owner to owner ratio of monthly long-term care costs was 1.2 at minimum and 2.3 at maximum. This study showed that monthly long-term care costs for pet owners were approximately half those of non-pet owners. Pet owners might use long-term care services less frequently, or use lighter care services.

Impact of number of functional teeth on independence of Japanese older adults.

AIM: To examine the relationship between the number of present and functional teeth at baseline and future incidence of loss of independence. METHODS: Participants were community-dwelling older individuals who participated in a comprehensive geriatric health examination conducted in Kusatsu town, Japan, between 2009 and 2015. The primary endpoint was the incidence of loss of independence among participants, defined as the first certification of long-term care insurance in Japan. The numbers of present and functional teeth at baseline were determined via an oral examination. Demographics, clinical variables (e.g., history of chronic diseases and psychosocial factors), blood nutritional markers, physical functions, and perceived masticatory function were assessed. RESULTS: This study included 1121 individuals, and 205 individuals suffered from loss of independence during the follow-up period. Kaplan-Meier estimates of loss of independence for participants with smaller numbers of present and functional teeth were significantly greater than for those with larger numbers of teeth. Cox proportional hazard analyses indicated that a smaller number of present teeth was not a significant risk factor after adjusting for demographic characteristics. However, the number of functional teeth was a significant risk factor after the adjustment (hazard ratio: 1.975 [1.168-3.340]). Additionally, higher hazard ratios were observed in other adjusted models, but they were not statistically significant. CONCLUSIONS: The number of functional teeth may be more closely related to the future incidence of loss of independence than the number of present teeth. This novel finding suggests that prosthodontic rehabilitation for tooth loss possibly prevents the future incidence of this life-event. Geriatr Gerontol Int 2022; 22: 1032-1039.

Osteoimmunology in periodontitis; a paradigm for Th17/IL-17 inflammatory bone loss.

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.

Factors Related to Acceptance to Use Care Technologies for Bathing Among Middle-Aged Adults: A Cross-Sectional Study.

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.

Evidence that dog ownership protects against the onset of disability in an older community-dwelling Japanese population.

OBJECTIVES: This study examined the association between dog and cat ownership, the onset of disability and all-cause mortality in an older population. Dog and cat owners take more regular exercise and have closer social relationships than non-owners. We further assess the beneficial effects of these moderating variables on the onset of disability and mortality. METHODS: Dog and cat ownership data were collected from 11233 community-dwelling adults age 65 years and older. These data were matched with data about the onset of disability held by the Japanese long-term care insurance system. Local registry data were used to ascertain all-cause mortality. RESULTS: During the approximately 3.5 year follow-up period, 17.1% of the sample suffered onset of disability, and 5.2% died. Logistic regression analysis indicated that, compared with a reference group of those who had never owned a dog (odds ratio fixed at 1.0), older adults who were currently dog owners had a significantly lower odds ratio of onset of disability (OR = 0.54 95% CI: 0.37-0.79). Our results further show that regular exercise interacts with dog ownership to reduce the risk of disability. The association of dog and/or cat ownership with all-cause mortality was not statistically significant. CONCLUSIONS: Dog ownership appears to protect against incident disability among older Japanese adults. Additional benefits are gained from ownership combined with regular exercise. Daily dog care may have an important role to play in health promotion and successful aging.

Association between Experience of Pet Ownership and Psychological Health among Socially Isolated and Non-Isolated Older Adults.

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.

Advances in Oncology in US and Japan: Focusing on Cancer and Infectious Diseases.

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.