Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: Social environment is often associated with health outcomes, but epidemiological evidence for its effect on oral frailty, a potential risk factor for aspiration, is sparse. This study aimed to assess the association between social environment and tongue pressure, as an important measure of oral function. The study focused on family structure, social networks both with and beyond neighbours, and participation in leisure activities. DESIGN: A population-based cross-sectional study. SETTING: Annual health check-ups in a rural community in Japan. PARTICIPANTS: A total of 1982 participants, all over 40 years old. Anyone with missing data for the main outcome (n=14) was excluded. OUTCOME MEASURES: Tongue pressure was measured three times, and the maximum tongue pressure was used for analysis. A multivariable adjusted regression model was used to calculate parameter estimates (B) for tongue pressure. RESULTS: Having a social network involving neighbours (B=2.43, P=0.0001) and taking part in leisure activities (B=1.58, P=0.005) were independently associated with higher tongue pressure, but there was no link with social networks beyond neighbours (B=0.23, P=0.77). Sex-specific analyses showed that for men, having a partner was associated with higher tongue pressure, independent of the number of people in the household (B=2.26, P=0.01), but there was no association among women (B=-0.24, P=0.72; P-interaction=0.059). CONCLUSIONS: Having a social network involving neighbours and taking part in leisure activities were independently associated with higher tongue pressure. Marital status may be an important factor in higher tongue pressure in men.

DOI： 10.1136/bmjopen-2016-014878

DOI： 10.1136/bmjopen-2016-014878

PubMed

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.atherosclerosis.2016.06.040

DOI： 10.1016/j.atherosclerosis.2016.06.040

Language：English   Publishing type：Research paper (scientific journal)  

DOI： http://dx.doi.org/10.1136/thoraxjnl-2015-206871

DOI： http://dx.doi.org/10.1136/thoraxjnl-2015-206871

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1097/PSY.0000000000000121

DOI： 10.1097/PSY.0000000000000121

Language：English   Publishing type：Research paper (scientific journal)  

DOI： https://doi.org/10.1161/JAHA.114.001241

DOI： https://doi.org/10.1161/JAHA.114.001241

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： https://doi.org/10.2188/jea.JE20110109

DOI： https://doi.org/10.2188/jea.JE20110109

Authorship：Lead author  

DOI： 10.1007/s11325-009-0319-6.

DOI： 10.1007/s11325-009-0319-6.

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Epidemiological Association  

BACKGROUND: Environmental and genetic factors are suggested to exhibit factor-based association with HDL-cholesterol (HDL-C) levels. However, the population-based effects of environmental and genetic factors have not been compared clearly. We conducted a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study to evaluate the population-based impact of smoking, drinking, and genetic factors on low HDL-C. METHODS: Data from 11,498 men and women aged 35-69 years were collected for a genome-wide association study (GWAS). Sixty-five HDL-C-related SNPs with genome-wide significance (P < 5 × 10-8) were selected from the GWAS catalog, and seven representative SNPs were defined, and the population-based impact was estimated using population attributable fraction (PAF). RESULTS: We found that smoking, drinking, daily activity, habitual exercise, egg intake, BMI, age, sex and the SNPs CETP rs3764261, APOA5 rs662799, LIPC rs1800588, LPL rs328, ABCA1 rs2575876, LIPG rs3786247, and APOE rs429358 were associated with HDL-C levels. The gene-environmental interactions on smoking and drinking were not statistically significant. The PAF for low HDL-C was the highest in men (63.2%) and in rs3764261 (31.5%) of the genetic factors, and the PAFs of smoking and drinking were 23.1% and 41.8%, respectively. CONCLUSIONS: The present study showed that the population-based impact of genomic factor CETP rs3764261 for low HDL-C was higher than that of smoking and lower than that of drinking.

DOI： 10.2188/jea.JE20210142

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Atherosclerosis Society  

AIMS: The association between dietary patterns and serum low density lipoprotein (LDL) cholesterol would be changing in recent dietary habits in Japan. We investigated the relationship between dietary patterns and serum LDL cholesterol in a large general population. METHODS: From the baseline survey of Japan Multi-Institutional Collaborative Cohort Study between 2005 and 2013, 27,237 participants (13,994 were women) aged 35-69 years were cross-sectionally analyzed. Using a semi-quantitative food frequency questionnaire, five major sex-specific dietary patterns were identified using factor analysis. We assessed serum LDL cholesterol by quintiles of dietary pattern factor score. RESULTS: We identified dietary patterns; "vegetable rich pattern" , "meat and fried food rich pattern" and "high bread and low rice pattern" in women and men; "fish and shellfish rich pattern" and "high confectioneries and low alcohol pattern" in men; "healthy Japanese diet pattern" and "high alcohol and low rice pattern" in women. Serum LDL cholesterol in men was associated with "high bread and low rice pattern" score (Q5 was 4.2 mg/dL higher than Q1, p for trend ＜0.001) and "high confectioneries and low alcohol pattern" scores (Q5 was 9.5 mg/dL higher than Q1, p for trend ＜0.001). In women, serum LDL cholesterol was associated with "high bread and low rice pattern" score (Q5 was 7.1 mg/dL higher than Q1, p for trend ＜0.001). CONCLUSION: Some recent dietary patterns in Japan were associated with serum LDL cholesterol. Serum LDL cholesterol was associated with high bread and low rice pattern in both sex, and high confectioneries and low alcohol pattern in men.

DOI： 10.5551/jat.63675

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Association of Exercise Epidemiology  

DOI： 10.24804/ree.2154

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: Previous studies using objective parameters have shown that irregular sleep is associated with the disease incidence, progression, or mortality. This study aimed to determine the association between subjective sleep duration and sleep regularity, with mortality in a large population. METHODS: Participants were from the Japan Multi-Institutional Collaborative Cohort study. We obtained information from each participant on sleep duration, sleep regularity, and demographics and overall lifestyle using self-administered questionnaires. We defined sleep regularity according to participants' subjective assessment of sleep/wake time regularity. Participants (n = 81,382, mean age: 58.1 ± 9.1years, males: 44.2%) were classified into 6 groups according to sleep duration and sleep regularity. Hazard ratios (HR) for time-to-event of death were calculated using the Cox proportional hazards model. RESULTS: The mean follow-up period was 9.1 years and the mean sleep duration was 6.6 h/day. Irregular sleep significantly increased the risk of all-cause mortality in all models compared with regular sleep (HR 1.30, 95% confidence interval; CI, 1.18-1.44), regardless of sleep duration. Multivariable analysis of the 6 groups by sleep pattern (sleep regularity and duration) showed irregular sleep and sleep durations of <6 h/day, 6 to <8 h/day, or ≥8 h/day were associated with a 1.2-1.5-fold increases in mortality, compared to regular sleep and sleep duration of 6 to <8 h/day. CONCLUSIONS: Our study shows an association between sleep irregularity and all-cause mortality in a large Japanese population. Our findings provide further confirmation of the need to consider not only sleep duration, but also the regularity aspect of sleep schedules.

DOI： 10.1016/j.sleh.2022.08.010

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.sleep.2022.09.020

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/OBJECTIVES: Low-carbohydrate diets (LCD) are useful for weight reduction, and 50-55% carbohydrate consumption is associated with minimal risk. Genetic differences were related to nutritional consumption, food preferences, and dietary patterns, but whether particular genetic differences in individuals influence LCD adherence is unknown. SUBJECTS/METHODS: We conducted a GWAS on adherence to LCD utilizing 14,076 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a previously validated semiquantitative food frequency questionnaire to estimate food consumption. Association of the imputed variants with the LCD score by Halton et al. we used linear regression analysis adjusting for sex, age, total dietary energy consumption, and components 1 to 10 by principal component analysis. We repeated the analysis with adjustment for alcohol consumption (g/day) in addition to the above-described variables. RESULTS: Men and women combined analysis without adjustment for alcohol consumption; we found 395 variants on chromosome 12 associated with the LCD score having P values <5 × 10-8. A conditional analysis with the addition of the dosage data of rs671 on chromosome 12 as a covariate, P values for all 395 SNPs on chromosome 12 turned out to be insignificant. In the analysis with additional adjustment for alcohol consumption, we did not identify any SNPs associated with the LCD score. CONCLUSION: We found rs671 was inversely associated with adherence to LCD, but that was strongly confounded by alcohol consumption.

DOI： 10.1038/s41430-022-01090-w

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PURPOSE: The association between metabolic syndrome (MetS) and the risk of death from cancer is still a controversial issue. The purpose of this study was to examine the associations of MetS and metabolically unhealthy obesity (MUHO) with cancer mortality in a Japanese population. METHODS: We used data from the Japan Multi-Institutional Collaborative Cohort Study. The study population consisted of 28,554 eligible subjects (14,103 men and 14,451 women) aged 35-69 years. MetS was diagnosed based on the criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) and the Japan Society for the Study of Obesity (JASSO), using the body mass index instead of waist circumference. The Cox proportional hazards analysis was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for total cancer mortality in relation to MetS and its components. Additionally, the associations of obesity and the metabolic health status with cancer mortality were examined. RESULTS: During an average 6.9-year follow-up, there were 192 deaths from cancer. The presence of MetS was significantly correlated with increased total cancer mortality when the JASSO criteria were used (HR = 1.51, 95% CI 1.04-2.21), but not when the NCEP-ATP III criteria were used (HR = 1.09, 95% CI 0.78-1.53). Metabolic risk factors, elevated fasting blood glucose, and MUHO were positively associated with cancer mortality (P <0.05). CONCLUSION: MetS diagnosed using the JASSO criteria and MUHO were associated with an increased risk of total cancer mortality in the Japanese population.

DOI： 10.1371/journal.pone.0269550

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s12529-021-10020-2

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Other Link： https://link.springer.com/article/10.1007/s12529-021-10020-2/fulltext.html

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Previous studies have reported that the number of pregnancies and childbirths affected the risk of cardiovascular diseases (CVDs). However, the influence of reproductive history on hypertension and obesity, which are important risk factors for CVDs, is still unclear. Moreover, this association may vary depending on menopausal status. We evaluated the association of reproductive history with hypertension and obesity using a large cross-sectional dataset from the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study). At the baseline survey, physical data, blood samples, and self-reported health questionnaires were collected. Participants with insufficient data were excluded, and 24,558 women from eight study regions were included in this study. Logistic regression analysis was conducted to evaluate the association of reproductive history with hypertension and obesity using multivariable-adjusted odds ratios. In premenopausal women, childbirth showed a generally protective effect on hypertension but not on obesity. In postmenopausal women, childbirth was positively associated with obesity and hypertension but not with hypertension after adjusting for BMI. In conclusion, reproductive history was associated with hypertension and obesity in a large Japanese population, and this association differed between premenopausal and postmenopausal women.

DOI： 10.1038/s41440-021-00820-0

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Previous studies have investigated the usefulness of microRNA (miRNA/miR) expression data for the early detection of colorectal cancer (CRC). However, limited data are available regarding miRNAs that detect CRC before clinical diagnoses. Accordingly, the present study investigated the early detectability of CRC by miRNAs using the preserved serum samples of the cohort participants affected with CRC within 2 years of study enrollment. First, the significant miRNAs were revealed using clinical CRC samples for a (seven early CRCs and seven controls) microarray analysis based on significance analysis of microarrays. Next, replicability was verified by reverse transcription-quantitative (RT-q)PCR (eight early CRCs and eight controls, together with 12 CRCs and 12 controls). Finally, early detectability was tested using the cohort samples of Japan Multi-Institutional Collaborative Cohort Study (17 CRCs and 17 controls) to reveal how a certain number of patients developed CRC within 2 years after participation. In the discovery phase, miRNA expression measurements were conducted using a 3D-Gene Human miRNA Oligo Chip for 2,555 miRNAs, and RT-qPCR analyses were performed to validate the replicability. In the first validation set with eight CRCs with early clinical stage and eight age- and gender-matched controls, miR-26a-5p and miR-223-3p demonstrated the highest diagnostic accuracy of area under the curve (AUC)=1.000 (sensitivity and specificity 100%). In an examination of the predictability of CRC incidence using pre-clinical cohort samples, miR-26a-5p demonstrated good predictability of advanced CRC incidence with an AUC of 0.840. Overall, the present study revealed serum miR-26a-5p as a potential early detection marker for CRC.

DOI： 10.3892/ol.2022.13207

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: The aim of the present study was to investigate the associations between breastfeeding and the prevalence of metabolic syndrome in community-dwelling parous women and to clarify whether the associations depend on age. METHODS: The present cross-sectional study included 11,118 women, aged 35-69 years. Participants' longest breastfeeding duration for one child and their number of breastfed children were assessed using a self-administered questionnaire, and their total breastfeeding duration was approximated as a product of the number of breastfed children and the longest breastfeeding duration. The longest and the total breastfeeding durations were categorized into none and tertiles above 0 months. Metabolic syndrome and cardiovascular risk factors (obesity, hypertension, dyslipidemia, and hyperglycemia) were defined as primary and secondary outcomes, respectively. Associations between breastfeeding history and metabolic syndrome or each cardiovascular risk factor were assessed using multivariable unconditional logistic regression analysis. RESULTS: Among a total of 11,118 women, 10,432 (93.8%) had ever breastfed, and 1,236 (11.1%) had metabolic syndrome. In participants aged <55 years, an inverse dose-response relationship was found between the number of breastfed children and the prevalence of metabolic syndrome; multivariable-adjusted odds ratios for 1, 2, 3, and ≥4 breastfed children were 0.60 (95% confidence interval [CI]: 0.31 to 1.17), 0.50 (95% CI: 0.29 to 0.87), 0.44 (95% CI: 0.24 to 0.84), and 0.35 (95% CI: 0.14 to 0.89), respectively. The longest and total breastfeeding durations of longer than 0 months were also associated with lower odds of metabolic syndrome relative to no breastfeeding history in participants aged <55 years. In contrast, all measures of breastfeeding history were not significantly associated with metabolic syndrome and cardiovascular risk factors in participants aged ≥55 years old. CONCLUSIONS: Breastfeeding history may be related to lower prevalence of metabolic syndrome in middle-aged parous women.

DOI： 10.1371/journal.pone.0262252

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Epidemiological Association  

BACKGROUND: The Japan Multi-institutional Collaborative Cohort (J-MICC) study was launched in 2005 to examine gene-environment interactions in lifestyle-related diseases, including cancers, among the Japanese. This report describes the study design and baseline profile of the study participants. METHODS: The participants of the J-MICC Study were individuals aged 35 to 69 years enrolled from respondents to study announcements in specified regions, inhabitants attending health checkup examinations provided by local governments, visitors at health checkup centers, and first-visit patients at a cancer hospital in Japan. At the time of the baseline survey, from 2005 to 2014, we obtained comprehensive information regarding demographics, education, alcohol consumption, smoking, sleeping, exercise, food intake frequency, medication and supplement use, personal and family disease history, psychological stress, and female reproductive history, and collected peripheral blood samples. RESULTS: The baseline survey included 92,610 adults (mean age: 55.2 [9.4] years, 44.1% men) from 14 study regions in 12 prefectures. The participation rate was 33.5%, with participation ranging from 19.7% to 69.8% in different study regions. The largest number of participants was in the age groups of 65-69 years for men and 60-64 years for women. There were differences in body mass index, educational attainment, alcohol consumption, smoking, and sleep duration between men and women. CONCLUSIONS: The J-MICC Study collected lifestyle and clinical data and biospecimens from over 90,000 participants. This cohort is expected to be a valuable resource for the national and international scientific community in providing evidence to support longer healthy lives.

DOI： 10.2188/jea.JE20200147

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

Introduction: Reduced tongue pressure is one of the causes of dysphagia. The purpose of this study was to investigate the relationship between dental findings and tongue pressure, and whether prosthetic treatment prevents reduced tongue pressure. Methods: This was a cross-sectional study. Participants were 745 community-dwelling adults and elderly persons in the Goto Islands in Nagasaki, who underwent a health checkup for residents in 2015 and 2016. Data were collected on gender; age; grip strength; hemoglobin; Creatinine (Cr); glycated hemoglobin (HbA1c); history of stroke; smoking, drinking, exercise, and walking habits; number of teeth; wearing of removable dentures; functional units of natural teeth (n-FTUs), fixed prostheses (nif-FTUs), and removable dentures (t-FTUs); and tongue pressure. The associations between each variable and tongue pressure were examined using multiple regression analysis. Next, those with 3 or fewer n-FTUs were selected, and differences in tongue pressure were compared between those with 3 or fewer nif-FTUs and those with 4 or more nif-FTUs, using a propensity score matching method. Results: Male gender, weak grip strength, low HbA1c, no drinking, and a low number of teeth were independent factors significantly associated with lower tongue pressure. Among participants with 3 or fewer n-FTUs, the 43 with 4 or more nif-FTUs showed significantly higher tongue pressure than the 43 with 3 or fewer nif-FTUs after propensity score matching, although the number of t-FTUs was not associated with tongue pressure. Discussion/Conclusion: Tooth loss was significantly associated with lower tongue pressure. It was suggested that fixed prosthesis treatment might prevent the reduction of tongue pressure, but removable dentures did not have such an effect.

DOI： 10.1159/000513599

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

<title>Abstract</title>Gout is a common type of acute arthritis that results from elevated serum uric acid (SUA) levels. Recent genome-wide association studies (GWASs) have revealed several novel single nucleotide polymorphism (SNPs) associated with SUA levels. Of these, rs10821905 of <italic>A1CF</italic> and rs1178977 of <italic>BAZ1B</italic> showed the greatest and the second greatest significant effect size for increasing SUA level in the Japanese population, but their association with gout is not clear. We examined their association with gout using 1411 clinically-defined Japanese gout patients and 1285 controls, and meta-analyzed our previous gout GWAS data to investigate any association with gout. Replication studies revealed both SNPs to be significantly associated with gout (<italic>P</italic> = 0.0366, odds ratio [OR] with 95% confidence interval [CI]: 1.30 [1.02–1.68] for rs10821905 of <italic>A1CF</italic>, <italic>P</italic> = 6.49 × 10^–3, OR with 95% CI: 1.29 [1.07–1.55] for rs1178977 of <italic>BAZ1B</italic>). Meta-analysis also revealed a significant association with gout in both SNPs (<italic>P</italic>_{<italic>meta</italic>} = 3.16 × 10^–4, OR with 95% CI: 1.39 [1.17–1.66] for rs10821905 of <italic>A1CF</italic>, <italic>P</italic>_{<italic>meta</italic>} = 7.28 × 10^–5, OR with 95% CI 1.32 [1.15–1.51] for rs1178977 of <italic>BAZ1B</italic>). This study shows the first known association between SNPs of <italic>A1CF</italic>, <italic>BAZ1B</italic> and clinically-defined gout cases in Japanese. Our results also suggest a shared physiological/pathophysiological background between several populations, including Japanese, for both SUA increase and gout susceptibility. Our findings will not only assist the elucidation of the pathophysiology of gout and hyperuricemia, but also suggest new molecular targets.

DOI： 10.1007/s13577-021-00485-4

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Other Link： http://link.springer.com/article/10.1007/s13577-021-00485-4/fulltext.html

Language：English   Publishing type：Research paper (scientific journal)  

DOI： https://doi.org/10.1159/000513599

DOI： https://doi.org/10.1159/000513599

Language：Japanese   Publishing type：Research paper (scientific journal)  

Prostate cancer is emerging as a significant global public health burden. The incidence and prevalence of prostate cancer has increased in Japan, as westernized lifestyles become more popular. Recent advances in genetic epidemiology, including genome-wide association studies (GWASs), have identified considerable numbers of human genetic factors associated with diseases. Several GWASs have reported significant loci associated with serum prostate-specific antigen (PSA) levels. One GWAS, which was based on classic GWAS microarray measurements, has been reported for Japanese so far. In the present study, we conducted a GWAS of serum PSA using 1000Genomes imputed GWAS data (n =1,216) from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study, to detect candidate novel genetic loci that influence serum PSA levels in Japanese. The association of SNPs/genetic variants with serum PSA as a continuous variable was tested using the linear Wald test. SNP rs10000006 in SGMS2 (sphingomyelin synthase 2) on chromosome 4 had genome-wide significance (P <5×10-8), and eight variants on three chromosomes (chromosomes 12, 14, 15) had genome-wide suggestive levels of significance (P <1×10-6). With an independent data set from the J-MICC Shizuoka Study (n = 2,447), the association of the SGMS2 SNP with blood PSA levels was not replicated. Although our GWAS failed to detect novel loci associated with serum PSA levels in the Japanese cohort, it confirmed the significant effects of previously reported genetic loci on PSA levels in Japanese. Importantly, our results confirmed the significance of KLK3 SNPs also in Japanese, implying that consideration of individual genetic information in prostate cancer diagnosis may be possible in the future.

DOI： 10.18999/nagjms.83.1.183

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

<title>Abstract</title><sec>
<title>Background</title>
Sarcopenia is associated with increased mortality among older adults. Sleep-related problems have been studied as factors related to sarcopenia. This study was conducted to determine the relationship between sleep-related problems and sarcopenia among Japanese community-dwelling older adults using data from the Nagasaki Islands Study.


</sec><sec>
<title>Methods</title>
This cross-sectional study analyzed data collected from 2017 to 2018. A total of 1592 older adults (575 men, 36.1%) aged 65 years or older participated. Sarcopenia was evaluated using the skeletal muscle mass index and grasp powers based on the criteria of the Asian Working Group for Sarcopenia. Odds ratios for sarcopenia were calculated using logistic regression analysis. Furthermore, subgroup analysis was performed based on the following tertiles of age: 65–70 years, 71–78 years, and 79–98 years.


</sec><sec>
<title>Results</title>
The number of participants with sarcopenia was 238 (14.9%). The median age of participants in the sarcopenia group (80 years; interquartile range: 74–84) was significantly higher than in the non-sarcopenia group (73 years; interquartile range 69–79; <italic>P</italic> &lt;  0.001). In the sarco<italic>p</italic>enia group, 70.9% of participants had difficulty initiating and/or maintaining sleep, sleep duration tended to be longer (<italic>P</italic> &lt;  0.001), and 33.3% of participants’ sleep duration was over 9 h. In a logistic regression analysis for sarcopenia, advancing age was the most prominent factor, and the adjusted odds ratio (95% confidence interval) of facing difficulty initiating and/or maintaining sleep was 1.60 (1.14–2.25). Despite longer sleep duration being a significant factor in the univariable analysis, it was not significant in the multivariable analysis. In the logistic regression analysis for sarcopenia among older adults aged 79–98 years, the odds ratio (95% confidence interval) among women was significantly low at 0.53 (0.33–0.83).


</sec><sec>
<title>Conclusions</title>
Sarcopenia is associated with difficulty initiating and/or maintaining sleep among Japanese older adults. In sarcopenia control measures, sleep/wake disorders related to insomnia are required to be evaluated in detail to help inform nursing and medical policy.


</sec>

DOI： 10.1186/s12877-020-01658-w

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Other Link： https://link.springer.com/article/10.1186/s12877-020-01658-w/fulltext.html

Language：English   Publishing type：Research paper (scientific journal)   Publisher：BMJ  

<sec><title>Background:</title>Anti-citrullinated protein antibody (ACPA) production is observed in several organs even prior to the onset of rheumatoid arthritis (RA), and oral mucosa is considered to be one of the important tissues. The presence of HLA-DRB1*SE closely associates with ACPA production. Saliva is considered to reflect the oral microbiota including periodontal disease. Alteration of oral microbiota of RA becomes to be normalized by DMARDs treatment, however, the interaction of HLA-DRB1*SE, ACPA and oral microbiota of RA patients remains to be elucidated.

</sec><sec><title>Objectives:</title>The Nagasaki Island Study, which had started in 2014 collaborating with Goto City, is intended for research of the preclinical stage of RA, including ACPA/HLA genotype screening and ultrasound and magnetic resonance imaging examinations in high-risk subjects. Using the samples accumulated in this cohort, we have tried to investigate the difference of oral microbiota among RA patients and healthy subjects regarding to ACPA and HLA-DRB1*SE.

</sec><sec><title>Methods:</title>Blood and salivary samples were obtained from 1422 subjects out of 4276 who have participated in the Nagasaki Island Study from 2016 to 2018. ACPA positivity was 1.7 % in total. Some of RA patients resided in Goto City participated in the Nagasaki Island Study. At this point, we selected 291 subjects, who were ACPA positive non-RA healthy subjects (n=22) and patients with RA (n=33, 11 subjects were ACPA positive and 22 ACPA negative respectively) as the case, age and gender matched ACPA negative non-RA healthy subjects (n=236) as the control. ACPA was measured by an enzyme-linked immunosorbent assay, and HLA genotyping was quantified by next-generation sequencing (Ref.1). The operational taxonomic unit (OUT) analysis using 16S rRNA gene sequencing were performed. The richness of microbial diversity within-subject (alpha diversity) was scaled via Shannon entropy. The dissimilarity between microbial community composition was calculated using Bray-Curtis distance as a scale, and differences between groups (beta diversity) were tested by permutational multivariate analysis of variance (PERMANOVA). In addition, UniFrac distance calculated in consideration of the distance on the phylogenetic tree were performed.

</sec><sec><title>Results:</title>Median age 70 y.o., % Female 58.8 %. Among RA and non-RA subjects, not alpha diversity but beta diversity was statistically significance (p=0.022, small in RA). In RA subjects, both alpha and beta diversity is small (p&lt;0.0001), especially significant in ACPA positive RA (Figure 1). Amongt RA subjects, presence of HLA-DRB1*SE did not show the difference but the tendency of being small of alpha diversity (p=0.29).

</sec><sec><title>Conclusion:</title>Our study has suggested for the first time the association of oral microbiota alteration with the presence of ACPA and HLA-DRB1*SE. Oral dysbiosis may reflect the immunological status of patients with RA.

</sec><sec><title>References:</title>[1]Kawaguchi S, et al. Methods Mol Biol 2018;1802: 22

</sec><sec><title>Disclosure of Interests:</title>None declared

</sec>

DOI： 10.1136/annrheumdis-2020-eular.5147

Language：English   Publishing type：Research paper (scientific journal)  

AIM: The cardio-ankle vascular index (CAVI) reflects functional arterial stiffness, which is related to endothelial dysfunction. CD34-positive cells carry out an important function in endothelial repair. However, there have been no reports assessing the association between CAVI and the number of circulating CD34-positive cells. METHODS: We carried out a cross-sectional study of 249 Japanese men, aged 60-69 years, who underwent annual health checkups between 2013 and 2015. As individuals with high levels of circulating CD34-positive cells might indicate the influence of consumptive reduction of circulating CD34-positive cells as a result of aggressive endothelial repair, participants were stratified by circulating CD34-positive cell levels, using the median value in this population (0.95 cells/μL) as the cut-off. RESULTS: For participants with low circulating CD34-positive cell levels, logarithmic values of circulating CD34-positive cells were inversely associated with CAVI (multivariable standardized parameter estimate [β] = -0.22, P = 0.014), but not for participants with high levels (β = -0.04, P = 0.638). In addition, even when no significant associations between CAVI and carotid intima-media thickness were detected for participants with low circulating CD34-positive cell levels (β = -0.02, P = 0.865), significant positive associations were identified for participants with high levels (β = 0.22, P = 0.028). CONCLUSIONS: As circulating CD34-positive cell count might indicate endothelial repair activity, the present results show that CAVI is affected by insufficient endothelial repair in individuals with low circulating CD34-positive cell counts. Our results also show that a positive association between CAVI and carotid intima-media thickness exists only in individuals with aggressive endothelial repair, which indicates the presence of organic arterial disease, such as atherosclerosis. Geriatr Gerontol Int 2019; 19: 557-562.

DOI： 10.1111/ggi.13657

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Hypertension and atherosclerosis are bidirectionally related, while platelet count could serve as an indicator of endothelial repair. Therefore, high platelet counts could be associated with hypertension by indicating more intense endothelial repair activity. Furthermore, short stature has been shown to constitute a risk of atherosclerosis. Since inflammation-related single-nucleotide polymorphism (SNP (rs3782886)) is reportedly associated with myocardial infarction and short stature, rs3782886 could be associated with a high platelet count and thus more intense endothelial repair activity. METHODS: We conducted a cross-sectional study of 988 elderly Japanese who participated in a general health check-up. Short stature was defined as a height of at or under the 25th percentile of the study population, and high platelet count as the highest tertiles of the platelet levels. RESULTS: High platelet counts were found to be independently and positively associated with hypertension while rs3782886 was independently associated with high platelet levels and short stature. The classical cardiovascular risk factor-adjusted odds ratio (OR) and 95% confidence interval (CI) of high platelet count for hypertension was 1.34 (1.02, 1.77). With non-minor homo of the rs3782886 as the reference group, the adjusted OR and 95% CI for high platelet count and short stature of minor home were 2.40 (1.30, 4.42) and 2.21 (1.16, 4.21), respectively. CONCLUSION: SNP (rs3782886) was shown to be associated with high platelet count and short stature. This result partly explains how a genetic factor can influence the impact of height on endothelial repair.

DOI： 10.1186/s12199-019-0780-1

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND AND AIMS: Endothelial injury is well-known as a process that can lead to chronic kidney disease (CKD) and atherosclerosis. Hematopoietic activity is known to be associated inversely with CKD and positively with atherosclerosis. Since bone-derived progenitor cells (CD34-positive cells) contribute to endothelial repair (including the progression of atherosclerosis), understanding the association between CKD and carotid intima-media thickness (CIMT), in relation to circulating CD34-positive cell count, may be an efficient means of clarifying the mechanisms underlying endothelial activity. METHODS: We conducted a cross-sectional study of 570 elderly Japanese men aged 60-69 years, who underwent a general health check-up. Participants were stratified as per a median circulating CD34-positive cell count (1.01 cells/μL). RESULTS: Independent of the known cardiovascular risk factors, CIMT was found to be positively associated with CKD in the participants with high circulating CD34-positive cell counts but not in participants with low counts. Odds ratios were 1.40 (1.04, 1.89) for participants with high and 1.01 (0.72, 1.43) for participants with low circulating CD34-positive cell counts after adjustment for known cardiovascular risk factors at 95% confidence intervals for CKD with one standard deviation increment of CIMT. CONCLUSIONS: A positive association between CIMT and CKD was observed among participants with high circulating CD34-positive cell counts but not among participants with low counts. Endothelial repair activity might determine the association between CKD and CIMT.

DOI： 10.1016/j.atherosclerosis.2019.02.004

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Recent studies have revealed an inverse association between height and cardiovascular disease and that endothelial progenitor cells (CD34-positive cells) contribute to vascular maintenance, which is associated with cardiovascular disease. However, evidence of the association between height and CD34-positive positive cells among elderly participants is limited. To assess this association, we conducted a cross-sectional study of 231 elderly Japanese men aged 65-69. Since enhanced production of circulating CD34-positive cells in response to endothelial injury might act have a strong confounding effect on the association between height and circulating CD34-positive cells, the median value for the levels of these cells (0.93 cells/μL) was used to stratify the participants. Multivariable linear regression analysis demonstrated that height was significantly positively associated with circulating CD34-positive cells for those participants with low levels of circulating CD34-positive cells (n=114) but not for those with higher levels (n=117), with a multi-adjusted standardized parameter estimate (β) of 0.27 (p=0.008) for low and 0.11 (0.275) for higher circulating CD34-positive cell levels. The positive association is limited to participants with relatively low circulating CD34-positive cell levels, whose productivity of these cells is not activated. Our findings indicate that height is an indicator of vascular maintenance capability in elderly Japanese men.

DOI： 10.18632/aging.101768

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Hemoglobin concentration reportedly is positively associated with muscle strength, for example, handgrip strength. However, hemoglobin cannot repair muscle directly, but is beneficial only in a supportive role. Since hepatocyte growth factor (HGF) regulates muscle satellite cell production and differentiation, which is stimulated by organ injury, the supportive effect of hemoglobin should thus be stronger for participants with high HGF than for those with low HGF. However, the association between hemoglobin concentration and handgrip strength in relation to HGF levels remains unknown. METHODS: We conducted a cross-sectional study of 255 Japanese elderly men aged 60-69 years who participated in annual health check-ups in 2014-2015. The study population was categorized on the basis of a median value of HGF of 300.6 pg/mL. RESULTS: Among present study population, 128 participants showed low HGF. For participants with low HGF, hemoglobin concentration showed no significant association with handgrip strength (standardized parameter estimate (β) = 0.03, p = 0.767), but for those with high HGF, hemoglobin concentration was significantly positively associated with handgrip strength (β = 0.23, p = 0.014). CONCLUSIONS: A significant positive association between hemoglobin level and handgrip strength was established for elderly Japanese men aged 60-69 years with high HGF but not for participants with low HGF. Our finding indicates that HGF levels could determine the relationship of hemoglobin concentration with handgrip strength in elderly Japanese men aged 60-69 years. This result can be expected to serve as an effective tool for the clarification of the roles played by HGF and hemoglobin concentration in maintenance of muscle strength.

DOI： 10.1186/s12199-018-0744-x

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Patients with Yusho, a condition caused by exposure to dioxins and dioxin-like compounds, have diverse mental and physical complaints. However, the relationship between dioxins and sleep disorders has not yet been examined. This cross-sectional study was designed to investigate problems associated with sleep among patients with Yusho. METHODS: A total of 140 participants (52.9% men, average age: 67.1 ± 12.2 years) were examined using questionnaires and medical interviews by an expert on sleep medicine. Demographic and clinical characteristics, including blood concentrations of 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), which is the major cause of Yusho, were obtained from the results of recent surveys conducted by the Yusho Study Group. RESULTS: Moderate to severe symptoms of insomnia were present in 51.8% of the patients. The median Pittsburgh Sleep Quality Index global score (PSQI GS) was 8 (interquartile range: 5-11). The prevalence of restless legs syndrome/Willis-Ekbom disease (RLS/WED) was 30.7%; 24.3% of patients had severe RLS/WED (distressing symptoms with a frequency ≥ 1day per week). A higher blood concentration of 2,3,4,7,8-PeCDF (≥72.27 pg/g lipid) and severe RLS/WED were associated with higher odds of a PSQI GS ≥8, after adjusting for covariates (odds ratio [95% confidence interval]: 4.84 [1.10-21.25] and 4.15 [1.53-11.28], respectively). CONCLUSIONS: Symptoms of insomnia were frequent, and the prevalence of RLS/WED was high in patients with Yusho. In addition to the presence of RLS/WED, a higher blood concentration of 2,3,4,7,8-PeCDF was associated with lower subjective sleep quality.

DOI： 10.1016/j.envres.2018.05.033

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

AIM: The arterial pressure-volume index (API) and arterial velocity-pulse index (AVI) are novel measurement indices of arterial stiffness. This study was performed to examine the screening validity of the API and AVI for preclinical atherosclerosis in Japanese community-dwelling adults. METHODS: We conducted a cross-sectional study of 2,809 participants aged ≥40 years who underwent Japanese national medical check-ups from 2014 to 2016. Preclinical atherosclerosis was defined as a mean carotid intima-media thickness (CIMT) of ≥1.0 mm. Multivariable linear regression analysis was performed to investigate the association of CIMT with API and AVI, adjusting for body mass index, sex, and the Framingham-D'Agostino score. We also examined receiver operating characteristic curves, sensitivity, and specificity to predict preclinical atherosclerosis defined by the CIMT. The cardio-ankle vascular index was also measured for comparison with the API and AVI. RESULTS: Of 2,809 participants, 68 (2.4%) had preclinical atherosclerosis. In the multivariable linear regression analysis, the API and AVI maintained a positive association with the mean CIMT (B=2.6, P=0.009 and B=3.7, P=0.001, respectively). The cut-offs of the API and AVI that demonstrated better sensitivity and specificity for detection of subclinical atherosclerosis were 31 [area under the curve (AUC), 0.64] and 29 (AUC, 0.60). CONCLUSIONS: The API and AVI were positively associated with preclinical carotid atherosclerosis independent of the participants' cardiovascular risk. The ability of these scores to predict carotid atherosclerosis could make them a useful screening tool for atherosclerosis.

DOI： 10.5551/jat.43125

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Age-related low-grade inflammation causing endothelial disruption influences sarcopenia, hypertension, and atherosclerosis. We reported previously that maintenance of muscle strength in elderly hypertensive men with high platelet levels is positively associated with subclinical atherosclerosis but not in those with low platelet levels. Since reduced tongue pressure is related to sarcopenia, tongue pressure may be associated with subclinical carotid atherosclerosis in hypertensive elderly subjects, and platelet levels may function as an indicator of the association between tongue pressure and subclinical carotid atherosclerosis. METHODS: We conducted a cross-sectional study of 342 hypertensive elderly Japanese men aged 60-89 who participated in an annual health check-up in 2015 and 2016. Subclinical carotid atherosclerosis was defined as a common carotid intima-media thickness (CIMT) of 1.1 mm or more. RESULTS: In the overall study population, 171 subjects demonstrated low platelets (< 21.4 × 104/μL). Tongue pressure was significantly inversely associated with subclinical carotid atherosclerosis in these subjects, but not in subjects with high platelets. The known cardiovascular risk factor adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of subclinical carotid atherosclerosis for a 1 standard deviation (SD) increment in tongue pressure (10.4 kPa) were 0.54 (0.35, 0.85) and 1.31 (0.87, 1.96), respectively. CONCLUSION: Tongue pressure is inversely associated with subclinical carotid atherosclerosis in hypertensive elderly men with low platelet levels, but not in those with high levels. This finding may thus constitute an efficient tool for clarifying the background mechanism of age-related diseases such as sarcopenia, hypertension, and atherosclerosis.

DOI： 10.1186/s12199-018-0720-5

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

The association between human T-cell leukemia virus-1 (HTLV-1) and atherosclerosis remains to be determined. This case-control study aimed to investigate this association as measured by carotid intima-media thickness (CIMT). HTLV-1 infection was positively associated with CIMT, independent of atherosclerotic risks.

DOI： 10.1093/cid/ciy168

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

AIM: Although several risk factors contribute to the development of sarcopenia, whether preclinical atherosclerosis contributes to the risk of sarcopenia is not established. The present cross-sectional study aimed to investigate if there is an association between preclinical atherosclerosis and muscle strength among two ethnic populations. METHODS: Participants included individuals aged ≥40 years and enrolled in the third follow-up examination of the Andhra Pradesh Children and Parents Study, India, and in the baseline assessments of the Nagasaki Islands Study, Japan. Preclinical atherosclerosis was evaluated by carotid intima-media thickness, brachial-ankle pulse wave velocity, cardio-ankle vascular index. The association of carotid intima-media thickness and pulse wave velocity/cardio-ankle vascular index with handgrip strength (HGS) was analyzed separately in the sexes and for hypertensive status from the two cohorts using a multivariable linear regression model. RESULTS: Data on a total of 1501 participants in India and 3136 participants in Japan were analyzed. Carotid intima-media thickness was negatively associated with HGS in non-hypertensive Indian men (B coefficient = -5.38, P = 0.036). Arterial stiffness was also associated with HGS in non-hypertensive Indian men (B = -0.97, P = 0.001), but not in hypertensive Indian men. Same as Indian men, we found the significant associations between arterial stiffness and HGS in non-hypertensive women in both India and Japan (B = -0.44, P = 0.020, B = -0.63, P = 0.016, respectively), but not in hypertensive women. CONCLUSIONS: The negative association between preclinical atherosclerosis and HGS was dominantly found in non-hypertensive participants. Geriatr Gerontol Int 2018; 18: 1071-1078.

DOI： 10.1111/ggi.13312

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Hepatocyte growth factor (HGF) may act as a possible biochemical index for vascular damage, although evidence for the association between HGF and carotid intima-media thickness (CIMT) is limited. Since both HGF and circulating CD34-positive cells play an important role in endothelial repair, circulating CD34-positive cell levels may influence the association between HGF and CIMT. METHODS: We conducted a cross-sectional study of 269 elderly Japanese men aged 60-69 years who had undertaken an annual medical checkup from 2014 to 2015. RESULTS: The median value for circulating CD34-positive cells was 0.93 cells/μL. Among the study population, 135 men showed low circulating CD34-positive cell levels (≤ 0.93 cells/μL). By multivariable linear regression analysis, HGF was found to be significantly positively associated with CIMT only to participants with low circulating CD34-positive cell levels, with a multi-adjusted β of 0.26 (p = 0.005) and 0.002 (0.986) for low and high circulating CD34-positive cell levels, respectively. In addition, a significant interaction was observed between HGF and circulating CD34-positive cell levels (low and high) on CIMT (multivariable p value of 0.049). A positive association exists between HGF and CIMT in elderly Japanese men, limited to participants with low circulating CD34-positive cell levels. CONCLUSION: A positive association exists between HGF and CIMT in community-dwelling elderly Japanese men, which is limited to participants with low numbers of circulating CD34-positive cells. Our findings indicate that circulating CD34-positive cell levels could determine the influence of HGF on CIMT in elderly Japanese men.

DOI： 10.1186/s12199-018-0705-4

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

AIM: Maximum isometric tongue pressure (MIP) seems to have a diagnostic value for oral phase dysphagia. The present study aimed to examine the association between MIP and frailty, and to assess the screening validity of MIP for physical frailty. METHODS: We carried out a cross-sectional study, and enrolled participants aged ≥60 years from Japanese national medical check-ups in 2015 and 2016. The Fried frailty phenotype model was used. We analyzed odds ratios (OR) and 95% confidence intervals (CI) of physical frailty using one standard deviation increments of tongue pressure. Receiver operating characteristic curves were obtained to predict physical frailty using MIP values. RESULTS: Out of 1603 participants, 968 were categorized as non-frail, 605 as pre-frail and 30 as frail. In logistic regression analysis, one standard deviation increment of MIP significantly differentiated frail and pre-frail: the OR for frail with one standard deviation increment in MIP was 0.37 (95% CI 0.26-0.54, P < 0.001), and the OR for pre-frail was 0.63 (95% CI 0.57-0.70, P < 0.001). The area under the receiver operating characteristic curve for predicting frailty with MIP score was as high as 0.776 (95% CI 0.689-0.862). A point of MIP 35 kPa had a sensitivity of 90.0%, specificity of 40.4%, a positive likelihood ratio of 1.5 and a negative likelihood ratio of 0.2 for predicting frailty. CONCLUSIONS: MIP performance is independently associated with frailty. MIP also can be used as a simple screening tool for frailty. Geriatr Gerontol Int 2018; 18: 240-249.

DOI： 10.1111/ggi.13166

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Height is reported to be inversely associated with cardiovascular disease. And platelets play an important role in vascular remodeling by supporting CD34-positive cells. To clarify the association between height and platelet, we conducted a cross-sectional study of 219 elderly Japanese men. Since hemoglobin concentration is influenced by vascular remodeling activity, an analysis stratified by hemoglobin level was performed. An inverse association was seen between height and platelet count in subjects with a high hemoglobin concentration (≥ 14.5 g/dL), but not in subjects with a low hemoglobin concentration (< 14.5 g/dL). The standardized parameter estimates (β) were β = -0.22, p = 0.019 for subjects with high hemoglobin, and β = -0.01, p = 0.931 for subjects with low hemoglobin. We also found a positive association between platelets and carotid intima media thickness (CIMT) and circulating CD34-positive cells in subjects with high hemoglobin (partial correlation coefficient (r) = 0.21, p = 0.037 and r = 0.40, p =< 0.001), but not in subjects with low hemoglobin (r = 0.04, p = 0.710 and r = 0.06, p = 0.544). In subjects with a high hemoglobin concentration, platelets were inversely associated with height, and positively associated with CIMT and circulating CD34-positive cells. These results indicate that subjects with a short stature activate vascular remodeling to a much greater extent than subjects with a tall stature.

DOI： 10.18632/oncotarget.23660

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

AIM: Recent geriatric studies have focused on maximum voluntary tongue pressure against the palate (MTP) as a diagnostic value for dysphagia, as dysphagia causes aspiration pneumonia. Dysphagia can also cause water intake difficulties, resulting in hypernatremia by indicating the presence of hyperosmotic dehydration. However, no studies have reported on a possible association between reduced MTP and serum sodium levels. METHODS: To evaluate hyperosmotic dehydration within the normal range as an indicator of reduced MTP, we carried out a cross-sectional study of 655 older Japanese community-dwelling men (age ≥60 years) who undertook a general health check-up from 2015 to 2016. As a high concentration of glucose influences serum osmolarity, which might act as a strong confounding factor on this association, the additional analysis was limited to individuals without diabetes. Reduced MTP is defined as a tongue pressure at or under the 20th percentile of the study population (≤24.0 kPa). RESULTS: Independent of classical cardiovascular risk factors, the adjusted odds ratio of reduced MTP for a 1-standard deviation increment of serum sodium (2.21 mEq/L) was 1.29 (95% confidence interval 1.10-1.52). When the analysis was limited to individuals without diabetes, the association became slightly stronger, with an adjusted corresponding value of 1.59 (95% confidence interval 1.21-2.10). CONCLUSIONS: Serum sodium level within the normal range is independently associated with reduced MTP in older Japanese men. This finding suggests that measuring the MTP is clinically relevant for estimating the pathophysiological values (such as dysphagia risks and aspiration pneumonia risks) in daily clinical practice. Geriatr Gerontol Int 2018; 18: 183-186.

DOI： 10.1111/ggi.13152

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

AimHemoglobin is reported to be positively associated with hypertension. However, the underlying mechanism of this association is unknown. Recently, bone marrow-derived CD34-positive cells have been reported to play an important role in endothelial repair in conjunction with platelets. As the association between hypertension and endothelial dysfunction is bidirectional, the influence of endothelial repair also might strongly influence the association between hemoglobin and hypertension.
MethodsTo clarify the clinical importance of the hematological parameter on endothelial maintenance in older men, we carried out a cross-sectional study of 222 Japanese men aged 60-69years undergoing a general health checkup.
ResultsFor participants with a lower platelet count (21.0/L), hemoglobin was significantly positively associated with hypertension, but not for participants with a higher platelet count (&gt;21.0/L). The classical cardiovascular risk factor adjusted odds ratio of hypertension for 1-standard deviation increment of hemoglobin (1.0g/dL) was 2.09 (95% CI: 1.26, 3.48) for participants with a lower platelet count, and 1.07 (95% CI: 0.68, 1.67) for participants with a higher platelet count. We also found that although there was no significant correlation between hemoglobin and circulating CD34-positive cells for participants with a lower platelet count (=-0.06, P=0.603), a significant positive correlation was seen for participants with a higher platelet count (=0.29, P=0.004).
ConclusionsThe positive association between hemoglobin and hypertension was limited to participants with a lower platelet count as a result of insufficient endothelial repair. These results represent an efficient tool for clarifying the mechanism of endothelial maintenance that correlates with hypertension. Geriatr Gerontol Int 2017; 17: 2586-2592.

DOI： 10.1111/ggi.13068

Web of Science

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Triglycerides are reported to be positively associated with blood pressure (both systolic and diastolic). However, in a previous study, we reported a significant positive association between triglycerides and circulating CD34-positive cells (endothelial repair) among non-hypertensive, but not hypertensive, participants. Since hypertension and endothelial dysfunction have a bi-directional association (vicious cycle), the status of circulating CD34-positive cells may influence the association between triglycerides and hypertension. METHODS: Since antihypertensive medication use may influence results of the present study, we conducted a cross-sectional study of 327 community dwelling elderly (aged 60-69 years) Japanese participants who were not taking anti-hypertensive medication and who had participated in a general health check-up in 2013-2015. RESULTS: Participants were classified into two groups based on median values of circulating CD34-positive cells (0.93 cells/μL). For participants with lower circulating CD34-positive cells (n = 165), a significant positive association was seen between triglycerides and blood pressure, but not for participants with higher circulating CD34-positive cells (n = 162). The multivariable standardized parameter estimates (β) and p values of systolic blood pressure and diastolic blood pressure were 0.23 (p = 0.007) and 0.18 (p = 0.036) for participants with lower circulating CD34-positive cells and 0.08 (p = 0.409) and 0.03 (p = 0.786) for those with higher circulating CD34-positive cells. CONCLUSION: A significant positive association between triglycerides and blood pressure exists among those with lower, but not higher, circulating CD34-positive cells. The level of circulating CD34-positive cells acts as a determinant factor for the association between triglycerides and blood pressure.

DOI： 10.1186/s12199-017-0684-x

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

Aim: Bone-derived circulating CD34-positive cells are reported to play an important role in vascular maintenance. Additionally, height might influence age-related hematopoietic bone marrow decline, as it positively correlates with total bone marrow volume. As hypertension should mask the beneficial effects of circulating CD34-positive cells, hypertension status should account for this correlation. The present study aimed to clarify the clinical importance of height on vascular maintenance in older Japanese men.
Methods: We carried out a cross-sectional study of 343 older men aged 65-69 years who underwent a general health checkup from 2013 to 2015.
Results: Independent of known cardiovascular risk factors, height was found to be slightly, but significantly, positively correlated with the log number of circulating CD34-positive cells in systolic, but not non-systolic, hypertensive men. Multilinear regression analysis showed a parameter estimate (B) and standardized parameter estimate (beta) of 3.23 x 10(-2), 0.28 (P=0.003) for systolic hypertensive men and-0.49 x 10(-2), -0.04 (P=0.495) for non-systolic hypertensive men.
Conclusions: Height positively correlates with circulating CD34-positive cells in systolic, but not non-systolic, hypertensive men. As the beneficial effects of circulating CD34-positive cells on endothelial repair might be masked by hypertension where the production of CD34-positive cells is stimulated by hypertension-induced vascular damage, among individuals with systolic hypertension, circulating CD34-positive cells should indicate the limits of endothelial. repair. Therefore, height might indicate the capacity for adequate vascular maintenance in older men.

DOI： 10.1111/ggi.12876

Web of Science

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：IMPACT JOURNALS LLC  

Age-related disruption of microvascular endothelium exacerbates hypertension and sarcopenia; and atherosclerosis is a well-known biological response to vascular endothelial injury. Therefore, prevalence of atherosclerosis among hypertensive elderly subjects may partly indicate the presence of an appropriate response to endothelial injury. We conducted a cross-sectional study of 795 elderly hypertensive Japanese subjects aged 60-89 years. Since platelet level is an indicator of vascular repair activity, subjects were stratified by platelet counts. No significant association between handgrip strength and subclinical carotid atherosclerosis (carotid intimamedia thickness (CIMT) &gt;= 1.1mm) was observed for subjects with lower platelet counts, while a significant positive association was observed for subjects with higher platelets. Adjusted odds and 95% confidence intervals of subclinical carotid atherosclerosis for 1 standard deviation increments in handgrip strength were 0.86 (0.61, 1.22) for subjects with lower platelets and 1.82 (1.26, 2.64) for subjects with higher platelets. A positive association between handgrip strength and subclinical carotid atherosclerosis exists in hypertensive elderly subjects with higher, but not lower, platelet counts. These results lead us to speculate that subjects with a beneficial influence on prevention of sarcopenia (maintenance of handgrip strength) may possess the capacity of active endothelial repair that causes atherosclerosis.

DOI： 10.18632/oncotarget.20618

Web of Science

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

BACKGROUND: Although high-density lipoprotein-cholesterol (HDL) level is inversely correlated with cardiovascular events, HDL is also reported to be positively associated with hypertension, which is a known endothelial impairment factor. Since HDL mediates important protective actions on the vascular endothelium by increasing the number of circulating endothelial progenitor cells (CD34-positive cells), the level of circulating CD34-positive cells should influence the association between HDL and hypertension. METHODS: To investigate the association between HDL and hypertension in relation to the level of circulating CD34-positive cells, we conducted a cross-sectional study of 477 elderly men aged 60-69 years who participated in general health checkup. RESULTS: HDL was found to be significantly positively associated with hypertension in subjects with a high level of circulating CD34-positive cells, while no significant association was observed for subjects with low circulating CD34-positive cells. Known cardiovascular risk factors adjusted odds (ORs) and 95% confidence intervals (CIs) of hypertension for increments of one standard deviation (SD) in HDL (13.8 mg/dL) were 1.44 (1.06, 1.96) for subjects with a high level of circulating CD34-positive cells and 0.87 (0.63, 1.19) for subjects with low circulating CD34-positive cells. We also revealed a significant association between HDL level and CD34-positive cell level on hypertension, with fully adjusted p values for the effect of this interaction on hypertension at 0.022. CONCLUSIONS: Independent of known cardiovascular risk factors, HDL was found to be positively associated with hypertension in subjects with a high level of circulating CD34-positive cells but not for subjects with low circulating CD34-positive cells.

DOI： 10.1186/s40101-017-0143-9

Web of Science

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Background and aims: The bi-directional association between hypertension and endothelial dysfunction (vicious cycle) is crucial for the development of cardiovascular disease. Since platelets and circulating CD34-positive cells have been reported to contribute to vascular repair (endothelial repair and the development of atherosclerosis), these two factors could act as an indicator for the activity of this vicious cycle.
Methods: We conducted a cross-sectional study of 580 Japanese men aged 60-69 years who underwent an annual health check-up. Since aggressive endothelial repair might cause consumptive reduction of circulating CD34-positive cells, subjects were stratified by circulating CD34-positive count (&lt; 1.01 cells/mu L or &gt;= 1.01 cells/mu L).
Results: Platelet count is positively associated with hypertension among participants with a low CD34-positive cell count (multivariable-OR (odds ratio) for hypertension of 1 standard deviation (SD) increments in platelets (5.24 Chi 10(4)/mu L) = 1.47 (1.12, 1.91)), but not among participants with a high CD34-positive cell count (multivariable-OR = 0.91 (0.71, 1.18)). We also found that platelet count is positively associated with carotid intima-media thickness related to endothelial dysfunction among hypertensive participants with a low CD34-positive cell count (standardized parameter estimate (ss) = 0.26, p = 0.008), but not with a high CD34-positive cell count ( ss = 0.11, p = 0.234).
Conclusions: Our results indicate that the number of platelets and circulating CD34-positive cells acts as an indicator of the activity of the vicious cycle that exists between hypertension and endothelial dysfunction in elderly Japanese men. (c) 2017 Elsevier B. V. All rights reserved.

DOI： 10.1016/j.atherosclerosis.2017.02.016

Web of Science

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.14283/jfa.2016.107

DOI： doi: 10.14283/jfa.2016.107

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Background: Asian-specific single nucleotide polymorphism (SNPs) (rs3782886) is reported to be associated with myocardial infarction; sarcopenia is reported to be associated with coronary subclinical atherosclerosis. On the other hand, short stature has been revealed as an independent risk factor for cardiovascular disease. However, no studies have reported on the association between sarcopenia and short stature nor on the impact of rs3782886 on this association.
Methods: Since reduced maximum voluntary tongue pressure against the palate (MTP) reflects one aspect of sarcopenia, we conducted a cross-sectional study of 537 community-dwelling elderly Japanese participants aged 60-89 years who had participated in a general health checkup in 2015. Short stature was defined as values at or under the 25th percentile, and reduced MTP was defined as the lowest tertile of the study population (&lt;158.0 cm and &lt;26.5 kPa for men, &lt;145.0 cm and &lt;24.1 kPa for women).
Results: Independent of classical cardiovascular risk factors, short stature was revealed to be positively associated with reduced MTP. The adjusted-odds ratio (OR) and 95% confidence interval (CI) of reduced MTP for short stature was 1.87 (1.19, 2.94). We also found that independent of known cardiovascular risk factors, with the non-minor homo of rs3782886 taken as the reference group, the adjusted OR and 95% CI for short stature and reduced MTP of the minor homo allele were 3.06 (1.23, 7.63) and 3.26 (1.33, 8.03), respectively.
Conclusion: Short stature is independently associated with reduced MTP, with Asian-specific SNPs possibly playing an important role in this association.

DOI： 10.1186/s12199-017-0668-x

Web of Science

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： https://doi.org/10.1016/j.pmedr.2016.05.010

DOI： https://doi.org/10.1016/j.pmedr.2016.05.010

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s40101-016-0084-8.

DOI： 10.1186/s40101-016-0084-8.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1186/s40101-016-0085-7.

DOI： doi: 10.1186/s40101-016-0085-7.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.18632/aging.101061

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s12199-016-0532-4.

DOI： 10.1007/s12199-016-0532-4.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.18632/oncotarget.10229

DOI： 10.18632/oncotarget.10229

Language：English   Publishing type：Research paper (scientific journal)  

DOI： https://doi.org/10.1016/j.psyneuen.2016.04.005

DOI： https://doi.org/10.1016/j.psyneuen.2016.04.005

J-GLOBAL

Language：Japanese   Publisher：日本公衆衛生学会  

Language：Japanese   Publishing type：Research paper, summary (national, other academic conference)   Publisher：(一社)日本リウマチ学会  

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publisher：国立保健医療科学院  

地域の健康管理には、地域を把握するためのデータ収集・評価と、地域ぐるみで取り組むためのデータ活用が必要である。データ収集・評価では、取り組みの根拠を明確にするため、健康に関連する様々な情報を活用することが望ましい。大学と自治体が連携することで、疾病発症情報等様々な追加情報を得られることから、地域の疾病要因についての検証と評価が可能となる。また、大学が提供する分析結果を、行政や住民の強みを活かし伝わりやすい方法で示すことで、分野横断的な取り組みと、課題解決を後押しできると考えられる。本著では、大学が行う地域健診活動とコホート調査の調査手順について紹介し、地域で有用な情報を集める際の分野横断的な協働の必要性について説明した。また、自治体で入手しやすいデータの活用方法の工夫として、国保データベースシステム(KDB)データ・特定健診データの提示例と共に、公表機会の活用事例についても紹介した。分野横断的な協働の基盤となるのは、組織間や住民との信頼関係である。長崎大学と五島市の事例を通して重要であった活動基盤、視点と目標の共有、お互いの力が最大限に発揮できるよう情報提供し合える関係づくりについて説明した。(著者抄録)

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J03876&link_issn=&doc_id=20181122440004&doc_link_id=10.20683%2Fjniph.67.4_365&url=https%3A%2F%2Fdoi.org%2F10.20683%2Fjniph.67.4_365&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：日本公衆衛生学会  

Language：Japanese   Publisher：(公財)明治安田厚生事業団  

Andhra Pradesh Children and Parents Studyの第三次追跡調査およびNagasaki Islands Studyの2014〜2016年ベースライン調査参加者を対象とした。インドでは1501名、日本では3136名を解析した。インドでは、男性の割合が高く、年齢が若く、握力が男女ともに低く、頸動脈内膜中膜複合体厚(CIMT)も低く、高血圧症の割合が低かった。また、日本に比べて、HDLコレステロールが低く、中性脂肪が高く、中性脂肪/HDLコレステロール比が高値であった。インド男性でCIMT×高血圧症の有無を交互作用項とすると、CIMTと握力に負の関連を認めた。高血圧症での層別分析では、インドの非高血圧症男性でCIMTは握力と負の関連があった。インドの女性や日本のコホート集団においては有意な関連は認めなかった。年齢、BMI、収縮期血圧、空腹時血糖、総コレステロール、eGFR、アルブミン、脳卒中既往歴、虚血性心疾患既往歴、喫煙歴、飲酒歴、栄養摂取カロリー、蛋白摂取量、活動量を調整変数とした多変量解析で、インドのコホート集団でCIMTと四肢筋肉量との間に有意な関連は認めなかった。

CiNii Books

© 2018, Nagasaki University School of Medicine. All rights reserved. Aims: Slow walking speed in older subjects was reported to be associated with an increased risk of cardiovascular mortality. On the other hand, minor allele frequency of the single nucleotide polymorphism (SNP) rs3782886 is reported to be positively associated with coronary artery disease. Therefore, the rs3782886 genotype might be associated with walking speed later in life. However, no studies have reported on the influence of rs3782886 on walking speed in elderly subjects. Methods: To evaluate the influence of SNP rs3782886 on walking speed in later life, we conducted a cross-sectional study of 562 elderly women aged 60 years and over who had undertaken a general health check-up between 2014 and 2015. Faster walking speed was defined by a questionnaire which asked, “Do you walk faster than your contemporaries?” (yes, no). Results: Of the total study population, with regard to the rs3782886 genotype, 356 subjects showed major homo (A/A), 177 hetero (A/G) and 29 minor homo (G/G). Independent of known cardiovascular risk factors, with major homo as the reference group, the adjusted odds ratio and 95% confidence interval for faster walking speed were 0.92 (0.54, 1.58) for hetero and 0.39 (0.16, 0.97) for minor homo. Conclusion: Independent of classical cardiovascular risk factors, the SNP rs3782886 was found to be associated with faster walking speed, as defined by a questionnaire, in elderly Japanese women. This result represents an efficient tool to clarify the mechanism of rs3782886 as a risk factor for cardiovascular disease.

Scopus

J-GLOBAL

J-GLOBAL

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：(一社)日本内科学会  

BACKGROUND: Handgrip strength is a simple measurement of overall muscular strength and is used to detect sarcopenia. It also predicts adverse events in later life. Many mechanisms of sarcopenia development have been reported. A hypertensive status impairs endothelial dysfunction, which might deteriorate skeletal muscle if vascular angiogenesis is not maintained.OBJECTIVES: This study investigated muscle strength and circulating CD34-positive cells as a marker of vascular angiogenesis.DESIGN: Cross-sectional study.PARTICIPANTS: 262 male Japanese community dwellers aged 60 to 69 years.MEASUREMENTS: The participants&#039; handgrip strength, medical history, and blood samples were taken. We stratified the participants by hypertensive status to investigate the association between handgrip strength and circulating CD34-positive cells according to hypertensive status. Pearson correlation and linear regression analyses were used.RESULTS: In the Pearson correlation analysis, handgrip strength and the logarithm of circulating CD34-positive cells were significantly associated in hypertensive participants (r=0.22, p=0.021), but not in non-hypertensive participants (r=-0.01, p=0.943). This relationship was only significant in hypertensive participants (ß=1.94, p=0.021) in the simple linear regression analysis, and it remained significant after adjusting for classic cardiovascular risk factors (ß=1.92, p=0.020). The relationship was not significant in non-hypertensive participants (ß=-0.09, p=0.903).CONCLUSIONS: We found a positive association between handgrip strength and circulating CD34-positive cells in hypertensive men. Vascular maintenance attributed by circulating CD34-positive cells is thought to be a background mechanism of this association after hypertension-induced vascular injury in skeletal muscle.

DOI： 10.14283/jfa.2016.107

Scopus

PubMed

© 2017 Nagasaki University Library, All Right Reserved. Background: Although we reported in a previous study that diabetes with a high serum triglycerides to high-density lipoprotein cholesterol (TG-HDL) ratio constitutes a risk for atherosclerosis, associations in terms of TG-HDL ratio between diabetes and gamma-glutamyltransferase (GGT), which is also known as an independent risk factor for atherosclerosis, have not yet been clarified. The purpose of this study was to test the hypothesis that a positive association between GGT and diabetes may be confined to high TG-HDL. Methods: This was a cross-sectional study of 2,302 Japanese subjects who were undergoing a general health check in 2014. All subjects were divided into TG-HDL level tertiles and serum GGT and diabetes status were investigated. Results: Of 207 diabetes patients identified in this study, 94 had high TG-HDL, 63 intermediate TG-HDL, and 50 low TG-HDL. Independent of classical cardiovascular risk factors, serum GGT showed a positive association with diabetes in patients with high TG-HDL, but not in patients with intermediate and low TG-HDL diabetes. The multivariable adjusted odds ratios (OR) and 95% coincidence intervals (95%CI) of diabetes for 1 standard deviation (SD) increment of GGT were 1.64 (95%CI: 1.16-2.31) for high TG-HDL, 1.46 (95%CI: 0.95-2.26) for intermediate TG-HDL, and 1.04 (95%CI: 0.60-1.79) for low TG-HDL diabetes. Conclusion: Serum GGT is positively associated with diabetes in patients with high TG-HDL but not with intermediate or low TG-HDL diabetes. This finding may prove to be an efficient tool for estimating atherosclerotic risk in diabetes patients.

Scopus

J-GLOBAL

Event date： 2021.1

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<sec><title>Background:</title>Anti-citrullinated protein antibody (ACPA) production is observed in several organs even prior to the onset of rheumatoid arthritis (RA), and oral mucosa is considered to be one of the important tissues. The presence of HLA-DRB1*SE closely associates with ACPA production. Saliva is considered to reflect the oral microbiota including periodontal disease. Alteration of oral microbiota of RA becomes to be normalized by DMARDs treatment, however, the interaction of HLA-DRB1*SE, ACPA and oral microbiota of RA patients remains to be elucidated.

</sec><sec><title>Objectives:</title>The Nagasaki Island Study, which had started in 2014 collaborating with Goto City, is intended for research of the preclinical stage of RA, including ACPA/HLA genotype screening and ultrasound and magnetic resonance imaging examinations in high-risk subjects. Using the samples accumulated in this cohort, we have tried to investigate the difference of oral microbiota among RA patients and healthy subjects regarding to ACPA and HLA-DRB1*SE.

</sec><sec><title>Methods:</title>Blood and salivary samples were obtained from 1422 subjects out of 4276 who have participated in the Nagasaki Island Study from 2016 to 2018. ACPA positivity was 1.7 % in total. Some of RA patients resided in Goto City participated in the Nagasaki Island Study. At this point, we selected 291 subjects, who were ACPA positive non-RA healthy subjects (n=22) and patients with RA (n=33, 11 subjects were ACPA positive and 22 ACPA negative respectively) as the case, age and gender matched ACPA negative non-RA healthy subjects (n=236) as the control. ACPA was measured by an enzyme-linked immunosorbent assay, and HLA genotyping was quantified by next-generation sequencing (Ref.1). The operational taxonomic unit (OUT) analysis using 16S rRNA gene sequencing were performed. The richness of microbial diversity within-subject (alpha diversity) was scaled via Shannon entropy. The dissimilarity between microbial community composition was calculated using Bray-Curtis distance as a scale, and differences between groups (beta diversity) were tested by permutational multivariate analysis of variance (PERMANOVA). In addition, UniFrac distance calculated in consideration of the distance on the phylogenetic tree were performed.

</sec><sec><title>Results:</title>Median age 70 y.o., % Female 58.8 %. Among RA and non-RA subjects, not alpha diversity but beta diversity was statistically significance (p=0.022, small in RA). In RA subjects, both alpha and beta diversity is small (p&lt;0.0001), especially significant in ACPA positive RA (Figure 1). Amongt RA subjects, presence of HLA-DRB1*SE did not show the difference but the tendency of being small of alpha diversity (p=0.29).

</sec><sec><title>Conclusion:</title>Our study has suggested for the first time the association of oral microbiota alteration with the presence of ACPA and HLA-DRB1*SE. Oral dysbiosis may reflect the immunological status of patients with RA.

</sec><sec><title>References:</title>[1]Kawaguchi S, et al. Methods Mol Biol 2018;1802: 22

</sec><sec><title>Disclosure of Interests:</title>None declared

</sec>

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医学部4年生を対象とした科目「疫学と予防医学」のうち「疾患予防と健康施策」に関する講義を行った。