Vertical mother-to-infant transmission of herpes simplex virus 2 is correlated with tropism due to mutations in viral UL13.

Although neonates are commonly exposed to vaginal herpes simplex virus (HSV)-2, neonatal herpes is rare. Therefore, we analyzed paired infant and maternal HSV-2 isolates from two cases of mother-to-infant transmission to identify viral factors contributing to vertical transmission. Sixteen infant isolates with neonatal herpes and 27 genital isolates in their third trimester were included. The infant isolates were significantly more temperature-independent than the maternal isolates. Sequence comparison revealed viral UL13 protein kinase (UL13-PK) mutation in the infant isolates in both cases. In the expanded cohort, infant isolates (5/18) had significantly more UL13-PK mutations than genital isolates (1/29). Isolates within 8 days post-birth (3/4) had a significantly higher frequency of UL13-PK mutation than those after 9 days (2/14), suggesting a close association between UL13-PK mutations and vertical transmission. Elongation factor 1-delta was identified as a target of UL13-PK by proteomic analysis of UL13-PK-positive and -negative HepG2 cells. The mixed infant isolates with the intact and mutated UL13-PK conferred altered cell tropism, temperature independence adapting to fetal temperature, and better growth properties in Vero and hepatoblastoma HepG2 cells than in HSV-2 with intact and mutated UL13-PK alone, indicating that viral UL13-PK mutation is essential for vertical HSV-2 transmission.

Bivalent mRNA vaccine effectiveness against COVID-19 among older adults in Japan: a test-negative study from the VENUS study.

BACKGROUND: Bivalent COVID-19 vaccines have been implemented worldwide since the booster vaccination campaigns of autumn of 2022, but little is known about their effectiveness. Thus, this study holistically evaluated the effectiveness of bivalent vaccines against infection in older adults in Japan. METHODS: We adopted the test-negative design using COVID-19 test data of individuals, aged ≥ 65 years, residing in three municipalities in Japan, who underwent tests in medical institutions between October 1 and December 30, 2022. Logistic regression analyses were conducted to estimate the odds of testing positive according to vaccination status. Vaccine effectiveness was defined as (1 - odds ratio) × 100%. RESULTS: A total of 3,908 positive and 16,090 negative results were included in the analyses. Receiving a bivalent dose in addition to ≥ 2 monovalent doses was 33.6% (95% confidence interval [CI]: 20.8, 44.3%) more effective than receiving no vaccination, and 18.2% (95% CI: 9.4, 26.0%) more effective than receiving ≥ 2 monovalent doses but not receiving a bivalent vaccination. In addition, the effectiveness peaked at 14-20 days after administration and then gradually declined over time. Furthermore, a bivalent booster dose provided 18.6% (95% CI: 9.9, 26.5%) additional protection among those vaccinated with ≥ 2 monovalent doses, in the absence of a previous infection history. However, we did not find sufficient evidence of effectiveness of bivalent vaccines among previously infected older adults. CONCLUSIONS: Bivalent vaccines are effective against COVID-19 infections among older adults without a history of infection.

Changes in the utilization of outpatient and visiting dental care and per-attendance care cost by age groups during COVID-19 pandemic waves in Japan: A time-series analysis from LIFE study.

BACKGROUND: The influence of the coronavirus disease (COVID-19) pandemic on dental care utilization may have differed according to individual characteristics or type of dental care provision. This study aimed to evaluate the changes in dental care utilization and per-attendance costs by age group and type of dental care during the COVID-19 pandemic in Japan. METHODS: This time-series study used healthcare insurance claims data from 01/07/2019 to 09/27/2021 (143 weeks) from nine municipalities in Japan. Dental care utilization rate per week and average dental care cost per attendance by age groups (0-19y/20-64y/65-74y/≥ 75y) and types of dental care (outpatient/visiting) were used as outcome variables. COVID-19 pandemic waves in Japan were used as predictors: 1st (03/23/2020-05/17/2020), 2nd (06/22/2020-09/27/2020), 3rd (10/26/2020-02/21/2021), 4th (02/22/2021-06/07/2021), and 5th (07/05/2021-09/13/2021) waves. Fixed effect models were employed to estimate the proportional changes. RESULTS: In the fixed effect model, we observed large declines in dental care utilization during the 1st (17.0-22.0%) and 2nd waves (3.0-13.0%) compared to the non-pandemic wave period in all age groups. In contrast, the average dental care cost per attendance increased in all age groups by 5.2-8.6% during the 1st wave. CONCLUSIONS: During the initial wave of the COVID-19 pandemic in Japan, dental care utilization decreased in all age groups, whereas the average dental care cost per attendance increased. The COVID-19 pandemic may have changed the dental care provision pattern towards less frequent and more concentrated dental care to avoid the risk of infection.

A principal component analysis of metabolome and cognitive decline among Japanese older adults: cross-sectional analysis using Tohoku Medical Megabank Cohort Study.

BackgroundDementia is the leading cause of disability and imposes a significant burden on society. Previous studies have suggested an association between metabolites and cognitive decline. Although the metabolite composition differs between Western and Asian populations, studies targeting Asian populations remain scarce.MethodsThis cross-sectional study used data from a cohort survey of community-dwelling older adults aged ≥ 60 years living in Miyagi, Japan, conducted by Tohoku Medical Megabank Organization between 2013 and 2016. Forty-three metabolite variables quantified using nuclear magnetic resonance spectroscopy were used as explanatory variables. Dependent variable was the presence of cognitive decline (≤ 23 points), assessed by the Mini-Mental State Examination. Principal component (PC) analysis was performed to reduce the dimensionality of metabolite variables, followed by logistic regression analysis to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for cognitive decline.ResultsA total of 2,940 participants were included (men: 49.0%, mean age: 67.6 years). Among them, 1.9% showed cognitive decline. The first 12 PC components (PC1-PC12) accounted for 71.7% of the total variance. Multivariate analysis showed that PC1, which mainly represented essential amino acids, was associated with lower odds of cognitive decline (OR = 0.89; 95% CI, 0.80-0.98). PC2, which mainly included ketone bodies, was associated with cognitive decline (OR = 1.29; 95% CI, 1.11-1.51). PC3, which included amino acids, was associated with lower odds of cognitive decline (OR = 0.81; 95% CI, 0.66-0.99).ConclusionAmino acids are protectively associated with cognitive decline, whereas ketone metabolites are associated with higher odds of cognitive decline.

Tooth loss mediates the association between smoking and an increased risk of dementia among older adults: The JAGES prospective cohort study.

AIM: Tooth loss has various causes; however, its cause-specific effects on health outcomes remain unclear. This study evaluated whether the association between past/current smoking and risk of dementia was mediated by tooth loss. MATERIALS AND METHODS: This 9-year-follow-up prospective cohort study targeted adults aged ≥65 years. Dementia incidence during 2013-2019, smoking status (never, past/current) in 2010 and the number of remaining teeth (≤19, ≥20) in 2013 were the outcome, exposure and mediator, respectively. We used causal mediation analysis to fit the Cox proportional hazards model and estimated the hazard ratio (HR) and 95% confidence interval (CI) of the natural indirect effect (NIE) of smoking on dementia incidence through tooth loss and their mediated proportions. RESULTS: Among 32,986 participants (mean age 72.6 years [1 SD = 5.4]; men 48.4%), the dementia incidence during follow-up was 2.11/100 person-years. Tooth loss significantly mediated the association between past/current smoking and dementia incidence; the NIE of fewer remaining teeth for past/current smokers compared to never smokers was HR = 1.03 (95% CI: 1.02-1.05), and the mediated proportion was 18.0%. CONCLUSIONS: Tooth loss significantly mediates the association between past/current smoking and an increased risk of dementia among older adults.

Association between consumption of small fish and all-cause mortality among Japanese: the Japan Multi-Institutional Collaborative Cohort Study.

OBJECTIVE: Although small fish are an important source of micronutrients, the relationship between their intake and mortality remains unclear. This study aimed to clarify the association between intake of small fish and all-cause and cause-specific mortality. DESIGN: We used the data from a cohort study in Japan. The frequency of the intake of small fish was assessed using a validated FFQ. The hazard ratio (HR) and 95 % confidence interval (CI) for all-cause and cause-specific mortality according to the frequency of the intake of small fish by sex were estimated using a Cox proportional hazard model with adjustments for covariates. SETTING: The Japan Multi-Institutional Collaborative Cohort Study. PARTICIPANTS: A total of 80 802 participants (34 555 males and 46 247 females), aged 35-69 years. RESULTS: During a mean follow-up of 9·0 years, we identified 2482 deaths including 1495 cancer-related deaths. The intake of small fish was statistically significantly and inversely associated with the risk of all-cause and cancer mortality in females. The multivariable-adjusted HR (95 % CI) in females for all-cause mortality according to the intake were 0·68 (0·55, 0·85) for intakes 1-3 times/month, 0·72 (0·57, 0·90) for 1-2 times/week and 0·69 (0·54, 0·88) for ≥ 3 times/week, compared with the rare intake. The corresponding HR (95 % CI) in females for cancer mortality were 0·72 (0·54, 0·96), 0·71 (0·53, 0·96) and 0·64 (0·46, 0·89), respectively. No statistically significant association was observed in males. CONCLUSIONS: Intake of small fish may reduce the risk of all-cause and cancer mortality in Japanese females.

The association between objective and subjective oral health conditions and the presence of anorexia of aging among Japanese older Adults1.

Anorexia of aging is a risk factor for malnutrition among older adults. This study aimed to evaluate the association between objective and subjective oral health and anorexia among independent older adults. This cross-sectional study targeted independent older adults aged ≥65 years who participated in the Japan Gerontological Evaluation Study conducted in 2022. The outcome variable was the presence of anorexia, as assessed by the Simplified Nutritional Appetite Questionnaire. Exposure variables were dental status (≥20 teeth, 10-19 teeth with/without dentures, and 0-9 teeth with/without dentures) as objective oral health and oral health-related quality of life measured by five items of the short version of the Oral Impacts on Daily Performances (OIDP) (eating, speaking, smiling, emotional stability, and enjoying with others) as subjective oral health. We fitted the Poisson regression model, including possible confounders, and estimated prevalence ratios (PRs) and 95% confidence intervals. Among 19,787 participants (mean age: 74.6 years [1SD = 6.2], male: 48.5%), 9.0% were classified as having anorexia. After adjusting possible confounders, those with ≤19 teeth had a higher proportion of experiencing anorexia compared to those with ≥20 teeth; however, the association was less pronounced among those with dentures (0-9 teeth with dentures: PR = 1.48 [1.31-1.68], and 0-9 teeth without dentures: PR = 2.08 [1.65-2.63]). Even after adjusting for dental status, each item of OIDP was significantly associated with the presence of anorexia (all p < 0.05). The results showed that both objective and subjective poor oral health were significantly associated with a higher probability of developing anorexia of aging. Therefore, improving both objective and subjective oral health through appropriate dental care could contribute to maintaining appetite in later life.

Differences in prevalence of self-reported oral hypofunction between older adult patients with rheumatoid arthritis and the general older population: A cross-sectional study using propensity score matching.

OBJECTIVE: To examine the association between rheumatoid arthritis (RA) and oral hypofunction (OHF) using propensity score matching (PSM) to adjust for differences between older adults with RA and the general older adult population. METHODS: We conducted a cross-sectional survey among 189 older adults with RA in 2019 (mean age, 71.9 ± 3.6) and 47 178 independent older adult residents in 2016 (mean age, 71.6 ± 4.0), respectively. The questionnaire covered information on socio-demographic characteristics and OHF for both groups. Age, sex, educational level and smoking history were used to determine PSM. Prevalence ratios (PRs) and 95% confidence intervals (CIs) of self-reported OHF (fewer remaining teeth, decreased masticatory function, deterioration of swallowing function and oral dryness) were estimated using Poisson regressions. RESULT: OHF was observed in 44.4% of patients with RA and 27.5% of residents. Before PSM, the prevalence of OHF among patients with RA was higher than that of residents (PR, 1.75; 95% CI, 1.50-2.05). After PSM, there were 189 patients with RA and residents, and the prevalence of OHF among patients with RA was still higher (PR, 1.61; 95% CI, 1.22-2.13). Poisson regression showed that the prevalence of 19 or fewer teeth (PR, 1.06; 95% CI, 0.82-1.36), difficulties eating tough foods (PR, 1.18; 95% CI, 0.90-1.55), difficulties swallowing tea or soup (PR, 1.77; 95% CI, 1.19-2.63), and dry mouth (PR, 2.79; 95% CI, 1.90-4.07) was higher among patients with RA than residents. CONCLUSION: Compared with the general older adult population, patients with RA have a higher prevalence of self-reported OHF.

Dental prosthesis use moderates association between tooth loss and risk of depressive symptoms in older adults with severe tooth loss: The JAGES cohort trial.

PURPOSE: Depression is a leading cause of disability. Although tooth loss increases the risk of depressive symptoms, it is unclear whether dental prosthesis use moderates this risk. This study aimed to investigate whether dental prosthesis use moderates the association between tooth loss and new depressive symptoms in older adults. METHODS: This cohort study used data from the 2016 and 2019 Japan Gerontological Evaluation Study (JAGES). The participants were independent older adults aged ≥65 years without depressive symptoms in 2016. The onset of depressive symptoms in 2019 was the outcome variable. The explanatory variables were dental status (≥20 teeth, 10-19 teeth with or without dental prostheses, and 0-9 teeth with or without dental prostheses) in 2016. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated using Poisson regression models with potential confounders as covariates. RESULTS: The analysis included 50,169 participants (mean age: 72.8 [standard deviation, 5.4] years). During follow-up, the incidence of depressive symptoms was 11.3%. Compared to those who had ≥20 teeth, the RR of depressive symptom onset was highest among those who had 0-9 teeth without dental prostheses (RR, 1.27; 95% CI, 1.04-1.56), after the adjustment for confounders. However, this risk was lower in those with 0-9 teeth and dental prostheses (RR, 1.08; 95% CI, 1.01-1.15). CONCLUSIONS: These data highlight the potential of dental prostheses as an important factor in reducing the risk of depressive symptoms among individuals with severe tooth loss.

Association between Number of Teeth and Eating out of Home: A 2019 Statistical Survey of the Japanese Representative Population.

Eating out of home (EOH), with its diverse food options, can benefit those with difficulty preparing their meals, especially older adults. Oral health status may be a determinant of EOH, as food accessibility is influenced by oral health, but this association remains unclear. This cross-sectional study used merged data from two national statistical surveys conducted in 2019. Participants were individuals aged ≥ 65 years who responded to both surveys. The frequency of EOH (

Social disconnection and suicide mortality among Japanese older adults: A seven-year follow-up study.

BACKGROUND: Few prospective studies have examined the association between social disconnection and late-life suicide. Therefore, we conducted a large-scale prospective study of older adults in Japan to examine differences in suicide mortality according to specific aspects of social disconnectedness. METHODS: We conducted a nationwide baseline survey of functionally independent older adults (age ≥65 years) from 12 municipalities in Japan from 2010 to 2011. We followed the participants (n = 46,144) for cause of death through December 2017 using vital statistics. Social disconnection was assessed based on the indicators of eating alone, a lack of instrumental/emotional support, no participation in community activities, and no contact with friends. We adopted Cox regression models with multiple imputation for missing values and calculated the population-attributable fraction (PAF). RESULTS: A total of 55 suicide deaths were recorded during an average follow-up of 7 years. Older adults with social disconnection had a marginally increased risk of suicide. The hazard ratio for eating alone vs. eating together was 2.81 (95% confidence interval [CI]: 1.47-5.37). The direction of these associations and point estimations did not largely change after controlling for depressive symptoms, an evident risk factor for suicidal behavior. The PAF indicated that eating alone was attributable to around 1800 (29%) of the suicide deaths among older adults annually in Japan. CONCLUSION: Avoidance of not only depressive symptoms, but also social disconnection including eating alone, is useful in suicide prevention among older adults.

Validity of claims-based definition of number of remaining teeth in Japan: Results from the Longevity Improvement and Fair Evidence Study.

BACKGROUND: Secondary healthcare data use has been increasing in the dental research field. The validity of the number of remaining teeth assessed from Japanese dental claims data has been reported in several studies, but has not been tested in the general population in Japan. OBJECTIVES: To evaluate the validity of the number of remaining teeth assessed from Japanese dental claims data and assess its predictability against subsequent health deterioration. METHODS: We used the claims data of residents of a municipality that implemented oral health screening programs. Using the number of teeth in the screening records as the reference standard, we assessed the validity of the claims-based number of teeth by calculating the mean differences. In addition, we assessed the association between the claims-based number of teeth and pneumococcal disease (PD) or Alzheimer's disease (AD) in adults aged ≥65 years using Cox proportional hazards analyses. RESULTS: Of the 10,154 participants, the mean number of teeth assessed from the claims data was 20.9, that in the screening records was 20.5, and their mean difference was 0.5. During the 3-year follow-up, PD or AD onset was observed in 10.4% (3,212/30,838) and 5.3% (1,589/30,207) of participants, respectively. Compared with participants with ≥20 teeth, those with 1-9 teeth had a 1.29 (95% confidence interval [CI]: 1.17-1.43) or 1.19 (95% CI: 1.04-1.36) times higher risk of developing PD or AD, respectively. CONCLUSION: High validity of the claims-based number of teeth was observed. In addition, the claims-based number of teeth was associated with the risk of PD and AD.

Differences in cumulative long-term care costs by dental visit pattern among Japanese older adults: the JAGES cohort study.

BACKGROUND: Long-term care (LTC) costs create burdens on aging societies. Maintaining oral health through dental visits may result in shorter LTC periods, thereby decreasing LTC costs; however, this remains unverified. We examined whether dental visits in the past 6 months were associated with cumulative LTC insurance (LTCI) costs. METHODS: This cohort study of the Japan Gerontological Evaluation Study targeted independent adults aged ≥65 years in 2010 over an eight-year follow-up. We used data from a self-reported questionnaire and LTCI records from the municipalities. The outcome was cumulative LTCI costs, and exposure was dental visits within 6 months for prevention, treatment, and prevention or treatment. A two-part model was used to estimate the differences in the predicted cumulative LTCI costs and 95% confidence intervals (CIs) for each dental visit. RESULTS: The mean age of the 8,429 participants was 73.7 years (standard deviation [SD]=6.0), and 46.1% were men. During the follow-up period, 17.6% started using LTCI services. The mean cumulative LTCI cost was USD 4877.0 (SD=19082.1). The predicted cumulative LTCI costs were lower among those had dental visits than among those who did not. The differences in predicted cumulative LTCI cost were -USD 1089.9 (95%CI = -1,888.5 - -291.2) for dental preventive visits, -USD 806.7 (95%CI = -1,647.4 - 34.0) for treatment visits, and -USD 980.6 (95%CI = -1,835.7 - -125.5) for preventive or treatment visits. CONCLUSIONS: Dental visits, particularly preventive visits, were associated with lower cumulative LTCI costs. Maintaining oral health through dental visits may effectively reduce the LTCI costs.

Hangeshashinto-Associated Mesenteric Phlebosclerosis and Highly Atypical Adenoma Requiring Laparoscopic Right Hemicolectomy.

Mesenteric phlebosclerosis is a rare ischemic colonic disorder caused by impaired venous drainage. Its prevalence is higher in East Asia, where herbal medicine is widely used. Treatment remains controversial. A 76-year-old woman who had taken Hangeshashinto, an herbal medicine, for 11 years was admitted for endoscopic treatment of high-grade dysplasia in the ascending colon. She had diarrhea and mesenteric phlebosclerosis diagnosed by abdominal computed tomography at age 71. At age 75, small polyps were detected in the ascending colon. A subsequent study revealed an increase in polyp size to 15 mm. Endoscopic mucosal resection failed to remove the lesion. A biopsy showed high-grade dysplasia with possible colon cancer risk. Conservative therapy did not improve mesenteric phlebosclerosis-related diarrhea; therefore, a laparoscopic right hemicolectomy was performed. Intraoperatively, the cecum was adherent to the abdominal wall and the right ovary. The specimen showed high-grade dysplasia in the mucosa and severe submucosal fibrosis. No metastasis was observed. This case shows the link between mesenteric phlebosclerosis and high-grade dysplasia in the ascending colon. Endoscopic mucosal resection was unsuccessful in removing the tumor. Endoscopic submucosal dissection was an alternative, but its safety in mesenteric phlebosclerosis-affected colonic segments remains uncertain. A laparoscopic right hemicolectomy was performed.

Genetic architecture of alcohol consumption identified by a genotype-stratified GWAS and impact on esophageal cancer risk in Japanese people.

An East Asian-specific variant on aldehyde dehydrogenase 2 (ALDH2 rs671, G>A) is the major genetic determinant of alcohol consumption. We performed an rs671 genotype-stratified genome-wide association study meta-analysis of alcohol consumption in 175,672 Japanese individuals to explore gene-gene interactions with rs671 behind drinking behavior. The analysis identified three genome-wide significant loci (GCKR, KLB, and ADH1B) in wild-type homozygotes and six (GCKR, ADH1B, ALDH1B1, ALDH1A1, ALDH2, and GOT2) in heterozygotes, with five showing genome-wide significant interaction with rs671. Genetic correlation analyses revealed ancestry-specific genetic architecture in heterozygotes. Of the discovered loci, four (GCKR, ADH1B, ALDH1A1, and ALDH2) were suggested to interact with rs671 in the risk of esophageal cancer, a representative alcohol-related disease. Our results identify the genotype-specific genetic architecture of alcohol consumption and reveal its potential impact on alcohol-related disease risk.