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Objectives: We investigated whether the positivity of anti-citrullinated peptide antibody (ACPA) is associated with cigarette-smoking status and human T-cell leukaemia virus type 1 (HTLV-1) infection in a general population in Nagasaki, Japan, which is an ageing and HTLV-1-endemic area. Method: Baseline data from community-dwelling people in the Nagasaki Islands Study (NaIS) were included in this cross-sectional analysis. ACPA and HTLV-1 were measured in 3887 subjects without a history of treatment for rheumatoid arthritis. A logistic regression analysis was performed to assess the relationship between ACPA positivity and candidates of correlation with ACPA, i.e. the cigarette-smoking status quantified by Brinkman's index (BI) and HTLV-1 positivity. Results: Fifty-one subjects (1.3%) showed ACPA positivity, and 650 subjects (16.6%) were HTLV-1 carriers. In an age- and gender-adjusted logistic regression analysis, the BI [odds ratio (OR) 1.09, 95% confidence interval (CI)1.02–1.14, p = 0.0031] and a BI value > 500 (OR 3.92, 95% CI 1.72–9.22, p = 0.0014) were each significantly associated with ACPA positivity. HTLV-1 positivity did not show any association with ACPA positivity. Conclusion: A significant effect of cigarette-smoking status on ACPA production was revealed, whereas HTLV-1 positivity was not associated with ACPA production in this general population. [ABSTRACT FROM AUTHOR]

The magnitude of the effect of human T-lymphotropic virus 1 (HTLV-1) infection on uveitis remains unclear. We conducted a cross-sectional study in a highly endemic area of HTLV-1 in Japan. The study included 4265 residents (men, 39.2%), mostly middle-aged and older individuals with a mean age of 69.9 years, who participated in our surveys between April 2016 and September 2022. We identified HTLV-1 carriers by screening using chemiluminescent enzyme immunoassays and confirmatory tests, and the proportion of carriers was 16.1%. Participants with uveitis were determined from the medical records of all hospitals and clinics where certified ophthalmologists practiced. We conducted logistic regression analyses in an age- and sex-adjusted model to compute the odds ratio (OR) and 95% confidence interval (CI) of uveitis according to HTLV-1 infection status. Thirty-two (0.8%) participants had uveitis. For HTLV-1 carriers, the age- and sex-adjusted OR (95% CI) of uveitis was 3.27 (1.57-6.72) compared with noncarriers. In conclusion, HTLV-1 infection was associated with a higher risk of uveitis among mostly middle-aged and older Japanese residents in a highly endemic HTLV-1 area. Our findings suggest that physicians who treat HTLV-1 carriers should assess ocular symptoms, and those who diagnose patients with uveitis should consider HTLV-1 infection., (© 2024 Wiley Periodicals LLC.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tsuji, Koga, Nonaka, Nobusue, Kawashiri, Yamanashi, Maeda, Arima, Aoyagi, Takahashi, Kawaguchi, Matsuda, Fujii, Kawano, Nakamura, Kawakami and Tamai.)

Height loss starting in middle age is reportedly significantly associated with death due to cardiovascular disease. Impaired blood flow is the main pathology in cardiovascular disease. Hematopoietic stem cells such as CD34-positive cells play an important role in maintaining the microcirculation and preventing impaired blood flow by activating endothelial repair and angiogenesis. Therefore, circulating CD34-positive cell count could be associated with height loss. To clarify the association between circulating CD34-positive cell count and height loss, we conducted a follow-up study of 363 Japanese men aged 60-69 years over 2 years. Height loss was defined as being in the highest quartile of height decrease per year. Independent of known cardiovascular risk factors, circulating CD34-positive cell count was significantly inversely associated with height loss. The fully adjusted odds ratio (OR) and 95% confidence interval (CI) of height loss for circulating CD34-positive cell count (logarithmic values) was 0.49 (0.32, 0.74). This study suggests that a lower capacity to maintain the microcirculation due to a fewer CD34-positive cells might affect height loss., (© 2022. The Author(s).)

Angiogenesis inhibition therapy causes hypertension by increasing peripheral vascular resistance. Vasa vasorum angiogenesis plays a crucial role in the development of atherosclerosis. Since vascular endothelial growth factor (VEGF), which contributes to the progress of angiogenesis, is reported to be inversely associated with the minor allele of polymorphism rs3025039, the minor allele of rs3025039 could be inversely associated with atherosclerosis among individuals with hypertension. A cross-sectional study of 1793 older Japanese adults aged 60-89 years with hypertension who participated in general health check-ups was conducted. Atherosclerosis was defined as carotid intima-media thickness (CIMT) ≥ 1.1 mm. The minor allele of polymorphism rs3025020 was positively associated with VEGF. Therefore, in addition to known cardiovascular risk factors, rs3025020 genotype acted as a confounding factor in the present study. Independent of known confounding factors, the minor allele of rs3025039 was inversely associated with atherosclerosis among older Japanese adults with hypertension. The fully adjusted odds ratio (OR) and 95% confidence interval (CI) for atherosclerosis with the minor allele of rs3025039 was 0.78 (0.64, 0.96). The angiogenesis-related polymorphism rs3025039 was associated with the development of atherosclerosis among older Japanese individuals. This study indicates that the development of atherosclerosis among older individuals might partly indicate a capacity for angiogenesis., (© 2022. The Author(s).)

Background: Aging is a process that increases oxidative stress. Increased oxidative stress leads to the development of atherosclerosis and mitochondrial dysfunction. Mitochondria contribute to energy production that might have a beneficial influence on maintaining muscle strength. Therefore, the height-related single nucleotide polymorphism (SNP) rs17081935, which is also reported to be associated with mitochondrial metabolism, might be associated with reduced muscle strength and this association might be affected by atherosclerosis status. To clarify those associations, a cross-sectional study of 1374 elderly Japanese individuals aged 60-89 years was conducted., Methods: Logistic regression was used to clarify the association between rs17081935 and reduced handgrip strength. Since atherosclerosis might affect handgrip strength, participants were stratified by atherosclerosis status. Reduced handgrip strength was defined as being in the lowest quintile of handgrip strength (< 25.6 kg for men and < 16.1 kg for women)., Results: No significant associations were found between a minor allele of rs17081935 and reduced handgrip strength among elderly participants without atherosclerosis. A significant inverse association was observed among elderly participants with atherosclerosis. After adjusting for known cardiovascular risk factors and height, the adjusted odd ratio (OR) and 95% confidence interval (CI) for reduced handgrip strength and a minor allele of rs17081935 were 1.13 (0.86, 1.43) for elderly participants without atherosclerosis and 0.55 (0.36, 0.86) for those with atherosclerosis, respectively., Conclusion: A minor allele of the height-related SNP rs17081935 was significantly inversely associated with reduced handgrip strength among older individuals with atherosclerosis, but not among those without atherosclerosis., (© 2021. The Author(s).)

Background: A positive association between handgrip strength and blood pressure has been reported. Since these factors are linked to the condition of the endothelium, the activity of endothelial repair might influence the association between handgrip strength and hypertension., Methods: A cross-sectional study was conducted with 257 Japanese men aged 60-69 years who underwent an annual health checkup. As individuals with high level of circulating CD34-positive cells might show active endothelial repair, which plays an important role in vascular homeostasis, participants were stratified by circulating CD34-positive cell levels, using the median value of this population (0.96 cells/μL) as the cutoff., Results: Independent of known cardiovascular risk factors, for participants with a high CD34-positive cell, handgrip strength is significantly positively associated with hypertension (odds ratio and 95% confidence interval of hypertension for 1 standard deviation increment of handgrip strength were 1.85 (1.19, 2.88) but not for participants with a low CD34-positive cell (0.91 (0.61, 1.37))., Conclusion: The positive association between handgrip strength and hypertension is limited to high CD34-positive cells. This result may help clarify the role of vascular homeostasis in maintaining muscle strength.

Background: Physical frailty is related to adverse outcomes, and poor oral health has been linked to malnourishment. Subjective measures of oral health-related quality of life (OHRQoL) have been used as indicators of the oral health problems of older adults, and they have been associated with malnourishment. This study aimed to assess OHRQoL's association with physical frailty., Methods: Cross-sectional study was conducted using data from the Nagasaki Islands Study that enrolled participants aged ≥60 years at Japanese national medical check-ups from 2014 to 2019. Physical frailty phenotype criteria were determined using the modified Fried frailty phenotype model. OHRQoL was assessed using the Geriatric Oral Health Assessment Index (GOHAI). Dentists conducted clinical dental examinations. Simple correlation and linear regression analyses were performed to investigate the associations of number of physical frailty phenotype criteria with GOHAI and other oral health indicators., Results: Among 1341 participants with a mean age of 72 years, GOHAI score was significantly associated with number of physical frailty phenotype criteria ( B  = -0.01, 95% confidence interval: -0.02 to -0.01, p  < 0.001). The association remained significant after adjustment for age, sex, body mass index, history of hypertension, history of diabetes mellitus, smoking status, Kessler-6 score, and number of remaining teeth., Conclusions: Oral health-related quality of life was associated with physical frailty in Japanese community-dwelling older adults., Competing Interests: The authors have stated explicitly that there are no conflicts of interest in connection with this article., (© 2021 The Authors. Journal of General and Family Medicine published by John Wiley & Sons Australia, Ltd on behalf of Japan Primary Care Association.)

Background: Recently, short stature has been revealed to be positively associated with hypertension, possibly because this indicates lower activity of vascular maintenance, such as angiogenesis. Vascular endothelial growth factor (VEGF) polymorphism (rs3025020) plays an important role in the progression of angiogenesis and may be associated with both hypertension and hypertension-associated short stature., Methods: A cross-sectional study of 1377 elderly Japanese individuals aged 60-89 years was conducted. Short stature was defined as the lowest tertile of height (< 160.8 cm for men and < 148.7 cm for women). Hypertension was defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg and/or antihypertensive medication use., Results: Independent of known cardiovascular risk factors, short stature was found to be positively associated with hypertension; the fully adjusted odds ratio (OR) and 95% confidence interval (CI) for hypertension were 1.51 (1.17, 1.96). With the reference group of carriers of the major allele of rs3025020, TT-homozygotes showed significantly lower OR for hypertension and short stature; the fully adjusted ORs (and 95% CIs) were 0.60 (0.41, 0.90) for hypertension and 0.59 (0.38, 0.91) for short stature, respectively., Conclusions: Angiogenesis-related genetic factor (rs3025020) is associated with hypertension and short stature, whereas short stature is positively associated with hypertension. Further investigation is necessary in this regard; the capacity for angiogenesis might partly explain the mechanism underlying the inverse association between height and hypertension.

Background: We investigated the association between psychological distress and oral health status/oral health-related quality of life (OHQoL) in Japanese community-dwelling people., Methods: We conducted a cross-sectional study using data from the Nagasaki Islands Study. A total of 1183 (455 men and 728 women) has been analyzed in this study. Psychological distress was measured using the Kessler Psychological Distress Scale (K6). Oral health status was measured by dental examination. The OHQoL was measured using the General Oral Health Assessment Index (GOHAI). We defined the total score of ≥5 points on the K6 as high psychological distress (high-K6 group)., Results: The multiple linear regression analysis to identify the GOHAI showed that gender, K6, the total number of teeth, the number of dental caries, and visiting a dental clinic within the past 6 months significantly associated with the GOHAI. Among all of these variables, high-K6 (≥ 5) was a substantial contributing factor of the GOHAI (β = - 0.23, 95% Cl - 2.31 to -1.41, p < 0.0001)., Conclusions: It is likely that the individual with high psychological distress was strongly related to poor OHQoL even in the general population.

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., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.

Age-related physical changes, such as low-grade inflammation and increased oxidative stress, induce endothelial repair and cause active arterial wall thickening by stimulating the production of CD34+ cells (the principal mediators of atherosclerosis). Despite this, aggressive endothelial repair (progressing atherosclerosis) might cause a wasting reduction in CD34+ cells, which could result in a lower capacity of endothelial repair and hypertension. As yet, no prospective study has clarified the association of circulating CD34+ cells with active arterial wall thickening. We conducted a prospective study of 363 men aged 60-69 years who participated in a general health check-up at least twice from 2014-2017. The circulating CD34+ cell count was significantly positively associated with active arterial wall thickening among subjects without hypertension (n = 236), but not among subjects with hypertension (n = 127). The fully adjusted odds ratios (ORs) of active arterial wall thickening for the logarithmic circulating CD34+ cell count were 1.83 (1.19, 2.84) and 0.69 (0.36, 1.32) for subjects without and with hypertension, respectively. Circulating CD34+ cells are positively associated with active arterial wall thickening in subjects without hypertension. This study demonstrates a means to clarify the mechanisms of endothelial repair in elderly subjects.

Background: Even though there is bidirectional association between hypertension and atherosclerosis, atherosclerosis itself is involved in the process of endothelial repair. To clarify the association of endothelial repair with hypertension, a cross-sectional study was conducted., Methods: We conducted a cross-sectional study of 562 elderly Japanese men aged 60-69. As gamma-glutamyl transpeptidase (γ-GTP) could act as a marker of oxidative stress that injures endothelial cell and higher levels of CD34-positive cell indicate a higher activity of endothelial repair, we therefore performed a CD34-positive level specific analysis of γ-GTP on atherosclerosis and hypertension., Results: In the present study population, hypertension was independently and positively associated with atherosclerosis (multivariable odds ratio (OR) = 2.09 (1.30, 3.35)). Among participants with high CD34-positive cells, γ-GTP showed significant and positive association with atherosclerosis (OR of the log-transformed value of γ-GTP (OR) = 2.26 (1.32, 3.86)) but not with hypertension (OR = 0.77 (0.51, 1.17)). Among participants with low CD34-positive cells, even γ-GTP showed no significant association with atherosclerosis (OR = 0.92 (0.51, 1.68)), but was significantly and positively associated with hypertension (OR = 1.99 (1.27, 3.12))., Conclusions: γ-GTP revealed to have ambivalent association with hypertension and atherosclerosis. Active endothelial repair that is associated with atherosclerosis might have beneficial association with hypertension.

In order to identify the causative agent of imported strongyloidiasis found in a Japanese mammalogist, who participated in a field survey in Tanzania, the hyper-variable region IV (HVR-IV) of 18S ribosomal DNA and partial mitochondrial cytochrome c-oxidase subunit 1 gene (cox1) were analyzed and compared with Strongyloides fuelleborni collected from apes and monkeys of Africa and Japan, and S. stercoralis from humans, apes and dogs. The HVR-IV and cox1 of the patient's worms were identical to or only slightly differed from those of worms parasitic in Tanzanian chimpanzees and yellow baboons, demonstrating that the patient acquired the infection during her field survey in Tanzania. Phylogenetic analysis with the maximum-likelihood method largely divided isolates of S. fuelleborni into three groups, which corresponded to geographical localities but not to host species. Meanwhile, isolates of S. stercoralis were grouped by the phylogenetic analysis into dog-parasitic and primate-parasitic clades, and not to geographical regions. It is surmised that subspeciation has occurred in S. fuelleborni during the dispersal of primates in Africa and Asia, while worldwide dispersal of S. stercoralis seems to have occurred more recently by migration and the activities of modern humans.