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Introduction: To allow the identification of IgG4-related disease (IgG4-RD) from a subclinical phase as it is important to understand the risk of elevated serum IgG4 levels. We planned to evaluate serum IgG4 levels in the participants of the Nagasaki Islands Study (NaIS), a large-scale health checkup cohort study. Methods: This study included 3,240 individuals who participated in the NaIS between 2016 and 2018 and consented to participate in the study. Serum IgG4, IgG, and IgE levels and human leukocyte antigen (HLA) genotyping results of the NaIS subjects as well as lifestyle habits and peripheral blood test results were analyzed. The magnetic bead panel assay (MBA) and the standard nephelometry immunoassay (NIA) were used to measure serum IgG4 levels. The data were evaluated using multivariate analysis to identify lifestyle and genetic factors associated with elevated serum IgG4 levels. Results: Serum IgG4 levels measured with the NIA and MBA showed a tight positive correlation between the two groups (correlation coefficient 0.942). The median age of the participants in the NaIS was 69 years [63–77]. The median serum IgG4 level was 30.2 mg/dL [IQR 12.5–59.8]. Overall, 1019 (32.1%) patients had a history of smoking. When the subjects were stratified into three groups based on the smoking intensity (pack-year), the serum IgG4 level was significantly higher among those with a higher smoking intensity. Accordingly, the multivariate analysis identified a significant relationship between smoking status and serum IgG4 elevation. Conclusion: In this study, smoking was identified as a lifestyle factor correlating positively with elevated serum IgG4 levels., Frontiers in Immunology, 14, art. no. 1124417; 2023

Structural arterial stiffness can be evaluated with carotid intima-media thickness (CIMT). Functional arterial stiffness can be evaluated with cardio-ankle vascular index (CAVI). A positive association between CIMT and tooth loss has been reported, but no studies have evaluated the association between CIMT and tooth loss in relation to functional arterial stiffness (functional atherosclerosis). A cross-sectional study of 1235 Japanese individuals aged 40–89 years was conducted. Tooth loss was defined as being in the lowest tertile for the number of remaining teeth (≤20 in men and ≤19 in women). Functional atherosclerosis was defined as CAVI ≥ 9.0. Independent of known confounding factors, CIMT was positively associated with tooth loss only in participants without functional atherosclerosis. Adjusted odds ratios for tooth loss and a 1 standard deviation increment in CIMT were 1.27 (1.04–1.55) for participants without functional atherosclerosis and 0.99 (0.77–1.26) for participants with functional atherosclerosis. CIMT and functional atherosclerosis had a significant effect on tooth loss; the fully adjusted p-value for the interaction on tooth loss was 0.019. Independent of known confounding factors, CIMT is positively associated with tooth loss only in participants without functional atherosclerosis. This finding helps clarify the influence of the progression of arterial stiffness on tooth loss because the progression of structural atherosclerosis might have a beneficial influence on the maintenance of the microcirculation., Journal of Clinical Medicine, 11 (14), art. no. 3993; 2022

Previous studies have reported a close correlation between vascular endothelial growth factor (VEGF), which plays an important role in angiogenesis, and human T-cell leukemia virus 1 (HTLV-1). However, an association between genetic characteristics related to VEGF and HTLV-1 infection has not yet been reported. Because the VEGF polymorphism rs3025039 is inversely associated with serum concentrations of VEGF, we focus on rs3025039 in the present study. To clarify the association between the VEGF polymorphism rs3025039 and HTLV-1 infection, a cross-sectional study of 1924 Japanese individuals aged 60–79 years who participated in general health check-ups was conducted. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) for HTLV-1 infection in relation to rs3025039 genotype were calculated with adjustment for known confounders. Compared with rs3025039 CC-homozygotes, (T) allele carriers had a significantly lower OR for HTLV-1 infection. The adjusted OR and 95% CI for HTLV-1 infection was 0.70 (0.54–0.91) (p = 0.009). Genetic characteristics related to lower angiogenesis activity might be associated with a lower chance of establishing HTLV-1 infection. Although further investigation is necessary, angiogenesis might play a crucial role in the establishment of HTLV-1 infection., Bioengineering, 9(10), art. no. 527; 2022

Reactivation of Epstein-Barr virus (EBV) is associated with the etiopathogenesis of a broad spectrum of diseases. This study aimed to investigate the association between psychological distress and EBV serological reactivation among community-dwelling older people and assess the role of sex differences in this association. This population-based cross-sectional survey was conducted among individuals who underwent annual health checkups (N = 2,821; median age 72.4 years). EBV serological reactivation was defined as elevation of EBV early antigen immunoglobulin G titers, and psychological distress was defined as Kessler 6 scores ≥5. Multivariable logistic regression analysis was performed to calculate odds ratios (OR) and 95% confidence intervals (CI) for EBV serological reactivation and psychological distress. EBV serological reactivation and psychological distress were detected in 16.4% and 8.7% of participants, respectively. Women accounted for 71% (328/463) of those with EBV serological reactivation. Multivariable logistic regression analysis showed psychological distress was not significantly associated with EBV serological reactivation among all participants (OR 1.31, 95% CI: 0.95, 1.82; P = 0.102). A sex-stratified multivariable analysis showed a positive association among women (OR 1.45, 95% CI: 1.01, 2.08; P = 0.043), but no association among men. EBV serological reactivation was independently associated with psychological distress in community-dwelling older women. The sex difference in our results warrants further investigation to clarify the physiological mechanisms underlying the association., Aging, 14(20), pp.8258-8269; 2022

Aggressive endothelial repair results in the progression of both structural and functional atherosclerosis, while insufficient endothelial repair worsens functional but not structural atherosclerosis. Aging increases the risk of inadequate endothelial repair. Since low-density lipoprotein cholesterol (LDLc) activates endothelial repair, LDLc may be positively associated with structural atherosclerosis but inversely associated with functional atherosclerosis in older individuals. This cross-sectional study analyzed 1458 participants aged 60 to 79 years. We defined structural atherosclerosis as a carotid intima-media thickness (CIMT) of at least 1.1 mm and functional atherosclerosis as a cardio-ankle vascular index (CAVI) of at least 9.0. LDLc was significantly positively associated with structural atherosclerosis and significantly inversely associated with functional atherosclerosis, independently of known cardiovascular risk factors. For 1 standard increment of LDLc (28 mg/dL for men and 29 mg/dL for women), the odds ratios and 95% confidence intervals after adjustment for known cardiovascular risk factors were 1.28 (1.10, 1.50) for structural atherosclerosis and 0.85 (0.75, 0.96) for functional atherosclerosis. LDLc activates endothelial repair, which results in the development of structural atherosclerosis but maintains endothelial function in older individuals. To evaluate atherosclerosis in clinical practice, the combination of structural and functional assessment of atherosclerosis could be informative., Nutrients, 15(1), art. no. 183; 2022

Sarcopenia is characterized by a progressive skeletal muscle disorder that involves the loss of muscle mass and low muscle strength, which contributes to increased adverse outcomes. Few studies have investigated the association between chronic infection and sarcopenia. This study aimed to examine the association between human T-cell lymphotropic virus type-1 (HTLV-1) and sarcopenia. We conducted a cross-sectional study and enrolled 2,811 participants aged ? 40 years from a prospective cohort study in Japanese community dwellers during 2017-2019. Sarcopenia was defined as low appendicular skeletal muscle mass and low handgrip strength. The association between HTLV-1 seropositivity and sarcopenia was assessed using multivariable logistic regression. Odds ratio (OR) and 95% confidence interval (CI) of sarcopenia were analysed using HTLV-1 seropositivity.We adjusted for age, sex, body mass index, physical activity, systolic blood pressure, glycated haemoglobin, low-density lipoprotein cholesterol, and smoking and drinking status. Of 2,811 participants, 484 (17.2%) HTLV-1 infected participants were detected. HTLV-1 infection was significantly associated with sarcopenia (adjusted OR 1.46, 95% CI 1.03-2.07, P = 0.034). HTLV-1 was associated with sarcopenia among community-dwelling adults.Active surveillance and early detection of asymptomatic HTLV-1 infection might be beneficial to reinforce countermeasures to inhibit the progress of HTLV infection-associated sarcopenia., Aging, 12(15), pp.15504-15513; 2020

BACKGROUND: Multimorbidity is the presence of two or more chronic diseases and is associated with increased adverse outcomes, including hospitalization, mortality and frequency of use of medical institutions. OBJECTIVE: This study aimed to describe multimorbidity patterns,determine whether multimorbidity was associated with high medical expenditure, and determine whether mental diseases had an interaction effect on this association.METHODS: We conducted a claims data-based observational study. Data were obtained for 7526 individuals aged 0-75 years from a medical claims data set for Goto, Japan, over a 12-month period (2016-17). Annual medical expenditure was divided into quintiles; the fifth quintile represented high medical expenditure. Multimorbidity status was defined as the occurrence of two or more health conditions from 17 specified conditions. Odds ratios (OR) and 95% confidence intervals (CI) for high medical expenditure were calculated by number of comorbidities. RESULTS: In total, 5423 (72.1%) participants had multimorbidity. Multimorbidity was significantly associated with high medical expenditure, even after adjustment for age, sex and income category (OR: 10.36, 95% CI: 7.57-14.19; P < 0.001). Mental diseases had a significant interaction effect on the association between multimorbidity and high medical expenditure (P = 0.001). CONCLUSIONS: Multimorbidity is associated with high medical expenditure in Japan. Mental diseases may contribute to increased medical costs., Family Practice, 37(4), pp.453-458; 2020