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Men with the TT genotype of the CYP19A1 polymorphism exhibited higher circulating estradiol levels than the TC + CC genotype. The TT genotype in the CYP19A1 polymorphism and the C allele of the ESR1 polymorphism, an allele increasing ESR1 expression, were associated with low serum CK activity after the ultramarathon. A combination of these polymorphisms was correlated with changes in the serum CK activity. Therefore, estrogen-related genetic polymorphisms partially predict exercise-induced muscle damage, that is, skeletal muscle membrane disruption.

Background Marital transitions are associated with adverse health events, such as mortality and cardiovascular disease. Since marital transitions (e.g., becoming widowed) are unavoidable life events, it is necessary to identify modifiable intermediate outcomes. Thus, we examined the association between marital transitions and vegetable intake among middle-aged and older Japanese adults. Methods This longitudinal study included Japanese adults aged 40-79 years who received an annual health checkup between 2007 and 2011 (baseline) and five years later (follow-up). Marital transitions were classified as whether and what type of transition occurred during the five-year period and comprised five groups: consistently married, married to widowed, married to divorced, not married to married, and remained not married. Changes in total vegetable, green and yellow vegetable, and light-colored vegetable intake from baseline to follow-up were calculated using the Food Frequency Questionnaire. Results Data from 4813 participants were analyzed (mean age: 59.4 years; 44.1% women). Regarding marital transitions, 3,960 participants were classified as "consistently married," 135 as "married to widowed," 40 as "married to divorced," 60 as "not married to married," and 529 as "remained not married." Multivariable linear regression analysis revealed that compared to consistently married, married to widowed was inversely associated with the change in total vegetable intake (β = -16.64, SE = 7.68, p = 0.030) and light-colored vegetable intake (β = -11.46, SE = 4.33, p = 0.008). Conclusion Our findings suggest that being widowed could result in a reduced intake of vegetables. Hence, dietary counseling according to marital situation is necessary.

Background We aimed to examine the association between educational history and second-hand smoke (SHS) exposure in Japanese adults. Methods We conducted a repeated cross-sectional study using data from the 2007-2011 baseline and the 2013-2016 follow-up survey in a Japanese suburban area. Overall, 5,562 male and 5,381 female non-smokers participated in the study, which evaluated the SHS exposure and educational history of the participants through self-reported questionnaires. We performed a multilevel ordered logistic regression analysis with survey year as the first level and the individual as the second level, SHS exposure as the dependent variable, educational history as the explanatory variable, and age, smoking history, marital status as covariates, stratified by gender and working status. Results The prevalence of SHS exposure was 45.4% in males and 41.9% in females in the 2007-2011 survey, and 31.6% in males and 28.7% in females in the 2013-2016 survey. Multilevel analysis indicated that less educational history was associated with higher SHS exposure in both genders (among males, the odds ratio compared with ≥13 years was 1.75 for 10-12 years and 1.64 for ≤9 years; among females, it was 1.79 for 10-12 years and 2.43 for ≤9 years). Stratified analysis by working status showed that for females, education-based inequalities in SHS exposure more strongly impacted for workers than non-workers (p for interaction Conclusions Education-based inequalities in SHS exposure exist in Japan and might be severe among female workers. Key messages Measures against SHS in Japan should be promoted to reduce social and gender inequalities.

Background It is known that physical activity affects glucose metabolism. However, there have been no reports on the influence of physical activity earlier in life on subsequent glucose metabolism. Therefore, we analyzed the influence of physical activity in earlier decades of life on insulin resistance in middle aged and older residents in Japan. Methods The subjects were 6,883 residents of Okazaki City between the ages of 40 and 79 years who underwent physical examinations at the Okazaki City Medical Association Public Health Center from April 2007 through August 2011. They gave informed consent for participation in the study. Data on individual characteristics were collected via a questionnaire and from the health examination records. Fasting blood glucose and insulin levels were used to calculate the homeostatic model assessment of insulin resistance (HOMA-IR). HOMA-IR >1.6 was considered to indicate insulin resistance for the purpose of logistic regression models. Results The study sample included 3,683 men and 3,200 women for whom complete information was available. For those who exercised regularly throughout their teens to their 30s-40s, the odds ratio for having insulin resistance was 0.75 (95% confidence interval [CI], 0.58-0.96) for men and 0.76 (95% CI, 0.58-0.99) for women after adjusting for other variables, including age, body mass index, and present physical activity. A linear trend was also observed in both men and women. Conclusions Subjects who have exercised regularly in the early decades of life are less likely to have insulin resistance later in life.

Supplemental digital content is available in the text., Purpose Although several genetic factors may play a role in leisure-time exercise behavior, there is currently no evidence of a significant genomewide association, and candidate gene replication studies have produced inconsistent results. Methods We conducted a two-stage genomewide association study and candidate single-nucleotide polymorphisms (SNP) association study on leisure-time exercise behavior using 13,980 discovery samples from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study, and 2036 replication samples from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center-2 study. Leisure-time physical activity was measured using a self-administered questionnaire that inquired about the type, frequency and duration of exercise. Participants with ≥4 MET·h·wk−1 of leisure-time physical activity were defined as exhibiting leisure-time exercise behavior. Association testing using mixed linear regression models was performed on the discovery and replication samples, after which the results were combined in a meta-analysis. In addition, we tested six candidate genetic variants derived from previous genomewide association study. Results We found that one novel SNP (rs10252228) located in the intergenic region between NPSR1 and DPY19L1 was significantly associated with leisure-time exercise behavior in discovery samples. This association was also significant in replication samples (combined P value by meta-analysis = 2.2 × 10−9). Several SNP linked with rs10252228 were significantly associated with gene expression of DPY19L1 and DP19L2P1 in skeletal muscle, heart, whole blood, and the nervous system. Among the candidate SNP, rs12612420 in DNAPTP6 demonstrated nominal significance in discovery samples but not in replication samples. Conclusions We identified a novel genetic variant associated with regular leisure-time exercise behavior. Further functional studies are required to validate the role of these variants in exercise behavior.

Coffee is one of the most widely consumed beverages worldwide, and its role in human health has received much attention. Although genome-wide association studies (GWASs) have investigated genetic variants associated with coffee consumption in European populations, no such study has yet been conducted in an Asian population. Here, we conducted a GWAS to identify common genetic variations that affected coffee consumption in a Japanese population of 11,261 participants recruited as a part of the Japan Multi-Institutional Collaborative Cohort (J-MICC) study. Coffee consumption was collected using a self-administered questionnaire, and converted from categories to cups/day. In the discovery stage (n = 6,312), we found 2 independent loci (12q24.12–13 and 5q33.3) that met suggestive significance (P −6). In the replication stage (n = 4,949), the lead variant for the 12q24.12–13 locus (rs2074356) was significantly associated with habitual coffee consumption (P = 2.2 × 10−6), whereas the lead variant for the 5q33.3 locus (rs1957553) was not (P = 0.53). A meta-analysis of the discovery and replication populations, and the combined analysis using all subjects, revealed that rs2074356 achieved genome-wide significance (P = 2.2 × 10−16 for a meta-analysis). These findings indicate that the 12q24.12-13 locus is associated with coffee consumption among a Japanese population.

The number of older adults who continue working after retirement is increasing in Japan. Little is known about how job conditions affect older adults' health. We examined the association between job conditions and health-related quality of life (HRQOL) during a five-year follow-up study.This study included participants aged 65 years or older from the Japan Multi-Institutional Collaborative Cohort Study in the Okazaki area recruited at baseline between 2007 and 2011 and followed up five years later. Participants completed a self-reported questionnaire on the physical and mental health aspects of HRQOL (SF-8™), employment status, and job conditions (job satisfaction, skill use, and job suitability).Data of 1,146 men and 522 women were analyzed (mean age: 69.1 and 68.6 years, respectively). Generalized mixed linear regression analysis revealed that, compared to the not-working group, skill use was positively associated with mental health aspects among men (skill use × time: β = 0.16, SE = 0.08, p0.05), while poor job satisfaction and job suitability were negatively associated with mental health aspects among women (job satisfaction, not satisfied × time: β = -0.93, SE = 0.47, p0.05; job suitability, not suitable × time: β = -1.06, SE = 0.50, p0.05).Regarding job conditions among older adults, skill use in men was marginally associated with mental health, and poor job satisfaction and suitability in women were negatively associated with mental health. Considering the job conditions of older workers is necessary to protect their mental health.

SummaryObjective Inconsistent results have been found in prior studies investigating the accuracy of self-reported waist circumference, and no study has investigated the validity of self-reported waist circumference among Japanese individuals. This study used the diagnostic standard of metabolic syndrome to assess the accuracy of individual's self-reported height, weight, and waist circumference in a Japanese sample. Methods Study participants included 7,443 Japanese men and women aged 35–79 years. They participated in a cohort study's baseline survey between 2007 and 2011. Participants' height, weight, and waist circumference were measured and their body mass index (BMI) was calculated. Self-reported values were collected through a questionnaire before the examination. Results Strong correlations between measured and self-reported values for height, weight, and BMI were detected. The correlation was lowest for waist circumference (men, 0.87; women, 0.73). Men significantly overestimated their waist circumference (mean difference, 0.8 cm), whereas women significantly underestimated theirs (mean difference, 5.1 cm). The sensitivity of self-reported waist circumference using the cut-off value of metabolic syndrome was 0.83 for men and 0.57 for women. Conclusions Due to systematic and random errors, the accuracy of self-reported waist circumference was low. Therefore, waist circumference should be measured without relying on self-reported values, particularly in the case of women.

Aim: Stroke is associated closely with vascular homeostasis, and several complex processes and interacting pathways, which involve various genetic and environmental factors, contribute to the risk of stroke. Although adrenomedullin (ADM) has a number of physiological and vasoprotective functions, there are few studies of the ADM receptor system in humans. The ADM receptor comprises a calcitonin-receptor-like receptor (CLR) and receptor activity-modifying proteins (RAMPs). We analyzed single nucleotide polymorphisms (SNPs) in the RAMP2 and CLR genes to determine their association with stroke in the light of gene-environment interactions. Methods: Using cross-sectional data from the Japan Multi-Institutional Collaborative Cohort Study in the baseline surveys, 14,087 participants from 12 research areas were genotyped. We conducted a hypothesis-based association between stroke prevalence and SNPs in the RAMP2 and CLR genes based on data abstracted from two SNPs in RAMP2 and 369 SNPs in CLR. We selected five SNPs from among the CLR variants (rs77035639, rs3815524, rs75380157, rs574603859, and rs147565266) and one RAMP2 SNP (rs753152), which were associated with stroke, for analysis. Results: Five of the SNPs (rs77035639, rs3815524, rs75380157, rs147565266, and rs753152) showed no significant association with obesity, ischemic heart disease, hypertension, dyslipidemia, and diabetes. In the logistic regression analysis, rs574603859 had a lower odds ratio (0.238; 95% confidence interval, 0.076–0.745, adjusted for age, sex, and research area) and the other SNPs had higher odds ratios for association with stroke. Conclusions: This was the first study to investigate the relationships between ADM receptor genes (RAMP2 and CLR) and stroke in the light of gene-environment interactions in human.

INTRODUCTION AND OBJECTIVE:Development of kidney stones has been linked to metabolic syndrome, which is characterized by insulin resistance (IR). In this prospective study, we followed the baseline...

Background: Second-hand smoke exposure has been associated with poor mental health. However, among Japanese adults, little is known about the association between second-hand smoking and depressive symptoms. We examined this association in a cross-sectional study among a Japanese general adult population sample. Methods: Japanese adults were recruited from the Japan Multi-Institutional Collaborative Cohort Study in the Okazaki area between 2012 and 2017. Second-hand smoke exposure and smoking status were assessed using a self-administered questionnaire. Based on their frequency of exposure to second-hand smoke, non-smokers and smokers were categorized as “almost never,” “sometimes,” and “almost every day”. Depressive symptoms were defined by a Kessler 6 score ≥5 points. We performed a multivariable Poisson regression analysis to obtain adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs) for depressive symptoms. Results: Overall, 5,121 participants (4,547 non-smokers and 574 smokers) were included whose mean age was 63.6 (standard deviation [SD], 10.3) years for non-smokers and 59.33 (SD, 10.2) years for smokers. The association between second-hand smoking and depressive symptoms was significant among non-smokers, but not among smokers. Among non-smokers, PRs compared with “almost never” were 1.25 (95% CI, 1.09–1.42) for “sometimes” and 1.41 (95% CI, 1.09–1.84) for “almost every day” (P for trend

Family caregiver burden is associated with higher psychological distress. However, little is known about the impact of neighbourhood relationships on caregivers' psychological distress. We examined whether neighbourhood relationships of caregivers moderate the association between family caregiver burden and psychological distress.This was a cross-sectional study.We recruited 5321 Japanese adults who participated in the Japan Multi-Institutional Collaborative Cohort Study in the Okazaki area between 2013 and 2017. Participants completed self-reported questionnaires to measure psychological distress (Kessler 6: K6), subjective caregiver burden, and neighbourhood relationships. We performed a multivariable linear regression analysis in which caregiver burden was designated as an independent variable and the K6 score as a dependent variable, adjusting for demographics. The interaction term between caregiver burden and neighbourhood relationships was also included in the analysis.Data from a total of 5069 participants were included (mean age [standard deviation]: 63.1 years [10.3 years]; 2226 [43.9%] female). Caregiver burden was significantly and positively associated with psychological distress (compared with no burden, mild burden: β = 0.24, P = 0.197; severe burden: β = 0.60, P 0.01; P for trend 0.01). There was a significant negative interaction effect of caregiver burden × neighbourhood relationship on psychological distress (severe burden × good neighbourhood relationship: β = -3.29, P 0.01).A higher caregiver burden was associated with higher psychological distress, and neighbourhood relationships moderated this association. Our findings suggest that good neighbourhood relationships can buffer caregiving-associated psychological distress.

INTRODUCTION AND OBJECTIVES:Kidney stone development has been linked to metabolic syndrome (MetS), which is characterized by insulin resistance. In a previous cross-sectional analysis, we reported ...

ObjectiveWe aimed to examine missing data in FFQ and to assess the effects on estimating dietary intake by comparing between multiple imputation and zero imputation.DesignWe used data from the Okazaki Japan Multi-Institutional Collaborative Cohort (J-MICC) study. A self-administered questionnaire including an FFQ was implemented at baseline (FFQ1) and 5-year follow-up (FFQ2). Missing values in FFQ2 were replaced by corresponding FFQ1 values, multiple imputation and zero imputation.SettingA methodological sub-study of the Okazaki J-MICC study.ParticipantsOf a total of 7585 men and women aged 35–79 years at baseline, we analysed data for 5120 participants who answered all items in FFQ1 and at least 50% of items in FFQ2.ResultsAmong 5120 participants, the proportion of missing data was 3·7%. The increasing number of missing food items in FFQ2 varied with personal characteristics. Missing food items not eaten often in FFQ2 were likely to represent zero intake in FFQ1. Most food items showed that the observed proportion of zero intake was likely to be similar to the probability that the missing value is zero intake. Compared with FFQ1 values, multiple imputation had smaller differences of total energy and nutrient estimates, except for alcohol, than zero imputation.ConclusionsOur results indicate that missing values due to zero intake, namely missing not at random, in FFQ can be predicted reasonably well from observed data. Multiple imputation performed better than zero imputation for most nutrients and may be applied to FFQ data when missing is low.

Usual sleep duration has substantial heritability and is associated with various physical and psychiatric conditions as well as mortality. However, for its genetic locus, only PAX8 and VRK2 have been replicated in previous genome-wide association studies (GWAS). We conducted a GWAS meta-analysis of self-reported usual sleep duration using three population-based cohorts totaling 31 230 Japanese individuals. A genome-wide significant locus was identified at 12q24 (p-value < 5.0 × 10-8). Subsequently, a functional variant in the ALDH2 locus, rs671, was replicated in an independent sample of 5140 Japanese individuals (p-value = 0.004). The association signal, however, disappeared after adjusting for alcohol consumption, indicating the possibility that the rs671 genotype modifies sleep duration via alcohol consumption. This hypothesis explained a modest genetic correlation observed between sleep duration and alcohol consumption (rG = 0.23). A Mendelian randomization analysis using rs671 and other variants as instrumental variables confirmed this by showing a causal effect of alcohol consumption, but not of coffee consumption on sleep duration. Another genome-wide significant locus was identified at 5q33 after adjusting for drinking frequency. However, this locus was not replicated, nor was the PAX8 and VRK2. Our study has confirmed that a functional ALDH2 variant, rs671, most strongly influences on usual sleep duration possibly via alcohol consumption in the Japanese population, and presumably in East Asian populations. This highlights the importance of considering the involvement of alcohol consumption in future GWAS of usual sleep duration, even in non-East Asian populations, where rs671 is monomorphic.

Purpose The purpose of this study was to evaluate the reproducibility and validity of a short food frequency questionnaire (FFQ) for food group intake in Japan, the reproducibility and partial validity of which were previously confirmed for nutrients. Methods A total of 288 middle-aged healthy volunteers from 11 different areas of Japan provided nonconsecutive 3-day weighed dietary records (DRs) at 3-month intervals over four seasons. We evaluated reproducibility based on the first (FFQ1) and second (FFQ2) questionnaires and their validity against the DRs by comparing the intake of 20 food groups. Spearman’s rank correlation coefficients (SRs) were calculated between energy-adjusted intake from the FFQs and that from the DRs. Results The intake of 20 food groups estimated from the two FFQs was mostly equivalent. The median energy-adjusted SRs between the FFQ1 and FFQ2 were 0.61 (range 0.38–0.86) for men and 0.66 (0.45–0.84) for women. For validity, the median de-attenuated SRs between DRs and the FFQ1 were 0.51 (0.17–0.76) for men and 0.47 (0.23–0.77) for women. Compared with the DRs, the proportion of cross-classification into exact plus adjacent quintiles with the FFQ1 ranged from 58 to 86% in men and from 57 to 86% in women. According to the robust Z scores and the Bland–Altman plot graphs, the underestimation errors in the FFQ1 tended to be greater in individuals with high mean levels of consumption for meat for men and for other vegetables for both men and women. Conclusion The FFQ demonstrated high reproducibility and reasonable validity for food group intake. This questionnaire is short and remains appropriate for identifying associations between diet and health/disease among adults in Japan.

There remain liver-related safety concerns, regarding potential hepatotoxicity in humans, induced by green tea intake, despite being supposedly beneficial. Although many randomized controlled trials (RCTs) of green tea extracts have been reported in the literature, the systematic reviews published to date were only based on subjective assessment of case reports. To more objectively examine the liver-related safety of green tea intake, we conducted a systematic review of published RCTs. A systematic literature search was conducted using three databases (PubMed, EMBASE and Cochrane Central Register of Controlled Trials) in December 2013 to identify RCTs of green tea extracts. Data on liver-related adverse events, including laboratory test abnormalities, were abstracted from the identified articles. Methodological quality of RCTs was assessed. After excluding duplicates, 561 titles and abstracts and 119 full-text articles were screened, and finally 34 trials were identified. Of these, liver-related adverse events were reported in four trials; these adverse events involved seven subjects (eight events) in the green tea intervention group and one subject (one event) in the control group. The summary odds ratio, estimated using a meta-analysis method for sparse event data, for intervention compared with placebo was 2.1 (95% confidence interval: 0.5–9.8). The few events reported in both groups were elevations of liver enzymes. Most were mild, and no serious liver-related adverse events were reported. Results of this review, although not conclusive, suggest that liver-related adverse events after intake of green tea extracts are expected to be rare.

Under the assumption that tryptophan (TRP) metabolism may be modulated by the intensity, duration, and total exercise/energy expenditure of the ultra-marathon, we evaluated the changes in two major TRP metabolic pathway substances [serotonin (5-HT) and kynurenine (KYN)] during a two-day ultra-marathon race. Blood was sampled at three different time points: before the race (baseline), after running 45 km on the first day, and after running 135 km on the second day. Serum TRP concentrations decreased in proportion to the distance covered, and the levels after running 135 km were significantly lower than at baseline and after running 45 km. Serum serotonin (5-HT) concentrations increased significantly after running 45 km but reduced towards baseline levels after running 135 km. Serum kynurenine (KYN) concentrations hardly changed after running 45 km but increased significantly after running 135 km compared with after running 45 km values. Serum FFAs levels increased significantly after running 45 km compared with baseline values, and they elevated even further after running 135 km. Serum albumin concentrations reduced significantly after running 45 km but remained at almost the same level after running 135 km. Serum 5-HT levels tended to be consistently correlated to the completion times on the first and second days. Serum 5-HT concentrations are known to be associated with central fatigue, and may predict exercise performance. KYN levels appeared to reflect the intensity of physical exercise, and its pathway may play a role in reactive oxygen species scavenging systems during a long-duration exercise.

We examined the association between family caregiver burden and subjective well-being with social participation&rsquo, s moderating effect among Japanese adults. Data were obtained from a cross-sectional survey by the Japan Multi-Institutional Collaborative Cohort Study in the Okazaki area between 2013 and 2017. Study participants included 5321 adults who visited the Public Health Center for annual health check-ups and answered a questionnaire regarding health status and lifestyle. Subjective well-being was assessed by a single item, out of 10 points, and analyzed with multivariable linear regression analysis models by subjective family caregiver burden (&ldquo, none&rdquo, &ldquo, mild&rdquo, severe&rdquo, ), stratified by gender. Ultimately, 2857 men and 2223 women were included. Mean participant age (standard deviation) in years was 64.7 (10.4) for men and 61.3 (10.0) for women. Multivariable analysis revealed that, among women, higher caregiver burden was inversely associated with subjective well-being (p for trend &lt, 0.001), and the interaction of severe caregiver burden and social participation on subjective well-being was positive and significant (p for interaction &lt, 0.05). High family caregiver burden was inversely associated with subjective well-being among Japanese women, but moderated by the caregiver&rsquo, s social participation, suggesting the importance of community development that enables family caregivers&rsquo, social participation to protect their subjective well-being.

The incidence rate of stomach cancer in Bali, Indonesia, is estimated to be strikingly lower than that in Japan. We conducted an on-site ecological study to investigate the association between the stomach cancer incidence and Helicobacter pylori (H. pylori) infection. Recruiting 291 healthy persons (136 men and 155 women) from the general population in Bali, Indonesia, we conducted a urea breath test (UBT) to examine H. pylori infection, along with a pepsinogen test to detect chronic atrophic gastritis and urine analysis to estimate sodium and potassium excretion. UBT positivities were 9% (2-15, 95% confidence interval) for men and 7% (1-12) for women, and positive cases for H. pylori IgG antibodies were 1% (0-3) for men and 3% (0-5) for women, significantly lower than the respective values in Japan. Positive pepsinogen tests in Bali were 0% (0-0) for men and 1% (0-4) for women, also significantly lower than the Japanese figures. Computed values for daily salt excretion were 13.3±4.1 g (mean ± SD) for men and 11.1±3.1 g for women, as high as corresponding Japanese consumption values. Moreover, the estimated potassium excretion was 3.2±0.7 g for men and 2.8±0.6 g for women in Bali, significantly higher than the figures in Japan. There were no associations across genetic polymorphisms of IL-beta, TNF-alpha, and PTPN11 with UBT positivity. The low incidence of stomach cancer in Bali may thus mainly be due to the rare H. pylori infection. Namely, the bacterium infection seems to be a critical factor for gastric cancer rather than host or other environmental factors.

Background: Helicobacter pylori is an important gastrointestinal pathogen related to the development of not only atrophic gastritis and peptic ulcer, but also gastric cancer. Human leukocyte antigens (HLA) may play particular roles in host immune responses to bacterial antigens. This study aimed to investigate the association between HLA-DQA1 and DQB1 genotypes and haplotypes vs H. pylori infection in an Indonesian population. Methods: We selected 294 healthy participants in Mataram, Lombok Island, Indonesia. H. pylori infection was determined by urea breath test (UBT). We analyzed HLA-DQA1 and DQB1 genotypes by PCR-RFLP and constructed haplotypes of HLA-DQA1 and DQB1 genes. Multiple comparisons were conducted according to the Bonferroni method. Results: The H. pylori infection rate was 11.2% in this Indonesian population. The DQB1*0401 genotype was noted to be associated with a high risk of H. pylori infection, compared with the DQB1*0301 genotype. None of the HLA-DQA1 or DQB1 haplotypes were related to the risk of H. pylori infection. Conclusions: The study suggests that HLADQB1 genes play important roles in H. pylori infection, but there was no statistically significant association between HLA-DQA1 or DQB1 haplotypes and H.pylori infection in our Lombok Indonesian population.

Objective: To investigate the utility of fluid-attenuated inversion recovery (FLAIR) imaging for diagnosing multiple system atrophy-parkinsonism (MSA-P). Methods: We retrospectively evaluated 49 subjects (19 with MSA-P including 11 with early-stage disease, 15 with Parkinson’s disease and 15 matched controls) in order to compare the diagnostic value of FLAIR imaging to detect a hyperintense putaminal rim (HPR) with that of T2-weighted (T2W) imaging. Results: Compared with T2W imaging, FLAIR imaging detected HPR more conspicuously in the 19 MSA-P patients (p = 0.01); this trend was also observed in 11 early-stage MSA-P patients (p = 0.01). Furthermore, FLAIR imaging tended to increase sensitivity of detecting HPR compared with T2W imaging (all patients: 89 vs. 58%, p = 0.07; early-stage patients: 100 vs. 55%, p = 0.06). Conclusions: FLAIR imaging might be more useful for detecting HPR in MSA-P patients, even though they are at an early stage.

The purpose of this research was to develop an infrared spectroscopic technique (Fourier transform infrared spectroscopy with attenuated total reflectance system; FTIR-ATR) for non-invasive measurement of saturated and unsaturated fatty acid compositions in human oral mucosa obtained from three nationalities; Iranian, Vietnamese, and Indonesian. The histogram patterns of fatty acid compositions for three nationalities suggest that the pattern of unsaturated fatty acids were quite different, although the distribution profiles of fatty acid to lipid ratios in FTIR-ATR has a similar normal pattern with small difference in skewness and mode. The second derivative infrared spectra of the mucosal tissues in the wavenumber regions from 1,600 to 1,760 cm(-1) and 2,800 to 3,050 cm(-1) were analyzed with partial least squares (PLS) multivariate regression analysis method. With this analysis method we compared predicted values with the measured values of ten categorized fatty acid compositions, i.e., a(saturated C17 or lower), b(C16:1 + C17:1), c(C18:0), d(C18:1), e(C18:2), f(saturated C20 or longer), g(C20:3 + C20:4), h(C22:1 + C24:1), i(C22:6), j(gammaC18:3). Almost all fatty acid compositions of oral mucosa were well predicted with differences between predicted and measured values within +/-5% of total, however, errors were relatively larger in minor components such as C22:6 than major components.

To investigate associations between plasma carotenoids, alpha-tocopherol and retinol with colorectal adenomas risk, we measured concentrations in 224 asymptomatic colorectal adenoma cases and 230 population-based controls matched for age and sex. After adjustment for age, history of colorectal adenomas and cancers, BMI, smoking, drinking status, multivitamin consumption and plasma total cholesterol, the risk of colorectal adenomas in the highest quartile was approximately half of that of men in the lowest quartile for alpha-carotene (OR=0.38; 95% CI: 0.18-0.84; P(trend)=0.01), beta-carotene (OR=0.51; 95% CI: 0.24-1.07; P(trend)=0.03) and total carotenoids (OR=0.48; 95% CI: 0.22-1.03; P(trend)=0.04). In addition, a protective association for alpha-carotene in women was also indicated, but which did not reach statistical significance (OR=0.53; 95% CI: 0.19-1.52; P(trend)=0.35). Our findings suggest a protective effect of carotenoids against the development of colorectal adenomas.

To investigate the correlation between the Helicobacter pylori (H. pylori) infection and host genetic background of healthy populations in Indonesia.In March 2007, epidemiological studies were undertaken on the general population of a city in Indonesia (Mataram, Lombok). The participants included 107 men and 187 women, whose ages ranged from 6 to 74 years old, with an average age of 34.0 (± 14.4) (± SD). The H. pylori of subject by UBT method determination, and through the polymerase chain reaction with confronting two-pair primers (PCR-CTPP) method parsing the single nucleotide polymorphism of interleukin (IL)-8, IL-4, IL-1β, CD14, tumor necrosis factor (TNF-α) and tyrosine-protein phosphates non-receptor type 11 (PTPN11) genotypes. The experimental data were analyzed by the statistical software SAS.The H. pylori infection rates in the healthy Indonesian population studied were 8.4% for men and 12.8% for women; no obvious differences were noted for H. pylori infection rates by sex or age. TC genotypes of IL-4, TC and CC genotypes of TNF-α, and GA genotypes of PTPN11, were higher in frequency. Both CC and TC genotype of TNF-α T-1031C loci featured higher expressions in the healthy Indonesian population Indonesia studied of (OR = 1.99; 95%CI: 0.67-5.89) and (OR = 1.66; 95%CI: 0.73-3.76), respectively. C allele of IL-1β T-31C gene locus was at a higher risk (OR = 1.11; 95%CI: 0.70-1.73) of H. pylori infection, but no statistical significance was found in our study.We reveal that the association between the TNF-α and IL-1β genotypes may be the susceptibility of H. pylori in the studied population.

Kazuyuki Arakawa,1,2 Akihiro Hosono,2 Kiyoshi Shibata,3 Reza Ghadimi,4 Mizuho Fuku,5 Chiho Goto,6 Nahomi Imaeda,7 Yuko Tokudome,8 Hideki Hoshino,9 Mitsuhiro Marumoto,1,2 Masaaki Kobayashi,10 Sadao Suzuki,2 Shinkan Tokudome1,2,11 1Department of Health and Nutrition Policy, 2Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; 3Department of Public Health and Nutrition, Aichi Gakusen University, Okazaki, Japan; 4Social Determinants of Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; 5Department of Rehabilitation Medicine, Yokohama Stroke and Brain Center, Yokohama, Japan; 6Department of Health and Nutrition, Nagoya Bunri University, Inazawa, Japan; 7Department of Food Science and Nutrition, Nagoya Women’s University, Nagoya, Japan; 8Department of Nutritional Sciences, Nagoya University of Arts and Sciences, Nisshin, Japan; 9Department of Early Childhood Studies, Aichi Bunkyo Women’s College, Inazawa, Japan; 10Department of Orthopaedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; 11National Institute of Health and Nutrition, Tokyo, Japan Abstract: We studied changes in blood markers of 18 nonprofessional, middle-aged runners of a 2-day, 130 km ultramarathon. Blood was sampled at baseline, after the goals on the first and second day, and at three time points (1, 3, and 5/6 days) after the race. Blood indices showed three patterns. First pattern indices showed essentially no changes after the two goals and after the race, including red blood cell indices, gamma-glutamyl transferase, and tumor necrosis factor-α. Second pattern markers, including the majority of indices, were elevated during the race (and also after the race for some parameters) and then returned to baseline afterward, including hemolysis/red blood cell destruction markers (indirect bilirubin) and an iron reservoir index (ferritin), muscle damage parameters (uric acid, creatine kinase, lactate dehydrogenase, and aspartate aminotransferase), renal function markers (creatinine and blood urea nitrogen), liver injury index (alanine aminotransferase), lipid metabolism indices (free fatty acid), reactive oxygen species and inflammation parameters (white blood cells, interleukin-6, and C-reactive protein), and energy production and catecholamines (adrenaline, noradrenaline, and dopamine). Third pattern index of a lipid metabolism marker – triglyceride – decreased during the race periods and started returning to baseline from then onward. Some hormonal markers such as insulin, leptin, and adiponectin showed unique patterns. These findings appeared informative for nonprofessional athletes to know about an optimal physical activity level, duration, and total exercise for elevating physical performance and monitoring physical/mental conditioning as well as for prevention of overtraining and physical injuries. Keywords: long-distance running, blood biochemical markers, anemia, muscle damage, lipid metabolism, inflammation

Changes in plasma thioredoxin (TRX) concentrations before, during, and after a 130-km endurance race were measured with the aim of elucidating the relationship between exercise and oxidative stress (OS).Blood samples were taken from 18 runners participating in a 2-day-long 130-km ultra-marathon during the 2 days of the race and for 1 week thereafter. There were six sampling time points: at baseline, after the goal had been reached on the first and second day of the endurance race, respectively, and on 1, 3, and 5/6 days post-endurance race. The samples were analyzed for plasma TRX concentrations, platelet count, and blood lipid profiles.Concentrations of plasma TRX increased from 17.9 ± 1.2 ng/mL (mean ± standard error of the mean) at baseline to 57.3 ± 5.0 ng/mL after the first day's goal had been reached and to 70.1 ± 6.9 ng/mL after the second day's goal had been reached; it then returned to the baseline level 1 day after the race. Platelet counts of 21.3 ± 1.2 × 10(4) cell/μL at baseline increased to 23.9 ± 1.5 × 10(4) cells/μL on Day 1 and to 26.1 ± 1.0 × 10(4) cells/μL on Day 2. On Day 7, the platelet counts had fallen to 22.1 ± 1.2 × 10(4) cell/μL. There was a significant positive correlation between plasma TRX and platelet count.These data suggest that plasma TRX is an OS marker during physical exercise. Further studies are needed to determine the appropriate level of exercise for the promotion of health.

Epidemiologic studies of n-3 fatty acids (FAs) and risk of colorectal cancer have generated inconsistent results, and relations with precursor colorectal adenomas (CRA) have not been evaluated in detail. We here focused on possible associations of serum FAs with CRA in the Japanese population.We conducted a case-control study of 203 asymptomatic CRA cases (148 men, 55 women) and 179 healthy controls (67 men, 112 women) during 1997-2003 in Nagoya, Japan. Baseline information was obtained using a lifestyle questionnaire and serum FA levels were measured by gas chromatography.A non-significant inverse association with CRA was observed for eicosapentaenoic acid (EPA) among women. Moreover, the concentrations of docosahexaenoeic acid (DHA), a major component of n-3 highly-unsaturated FAs (HUFAs), were significantly lower in cases in both sexes. In addition, serum concentrations of total FAs, saturated FAs (SFAs) and mono-unsaturated FAs (MUFAs) had strong positive links with CRA risk. In contrast, arachidonic acid (AA) and DHA were inversely related, with 66% and 59% risk reduction, respectively. Ratios of SFAs/n-3 PUFAs and SFAs/n-3 HUFAs exhibited significant positive relations with CRA risk but there was no clear link with n-6 PUFAs/n-3 PUFAs.Our findings suggest a promoting influence of SFAs and MUFAs along with a protective effect of DHA on CRA risk. However, further research is needed to investigate the observed discrepancy with the generally accepted roles of the AA cascade in carcinogenesis.

We investigated the possible influence of an exhaustive physical exercise on mental stress biomarkers (serotonin, tryptophan, and beta-endorphin) along with dopamine, noradrenaline and free fatty acids in an ultramarathon race in which 45 km was run on the first day and 90 km on the second. We obtained serum samples at 6 different time points during and after the race from 18 Japanese male runners who completed the marathon. Overall changes of serum serotonin and tryptophan concentrations were statistically significant according to ANOVA for repeated measurements (p < 0.05). Serum serotonin levels elevated rapidly on the first day with the post hoc Tukey's test. Tryptophan concentrations inversely decreased during the race, possibly because of utilization for synthesis of serotonin. Levels of beta-endorphin appeared to increase on the first and second days, but were not statistically significant. In conclusion, serum serotonin, tryptophan and beta-endorphin appeared to be used for mental stress markers in physical exercise.

The great variability in gastric cancer rates across Asia, with very high incidences in Japan and Korea, and exceedingly low incidences in ethnic Malays, whether in Malaysia or Indonesia, appears largely due to variation in Helicobacter pylori infection rates. While between 2% and 10.6% of gastric cancers in a recent Japanese survey were considered to be negative for bacterial infection on the basis of seropositivity and H. pylori-dependent mucosal atrophy, it is notoriously difficult to preclude past infection. The situation is greatly complicated by reported differences in the etiology of gastric cardia and non-cardia cancers. In the Western world there do appear to be tumours arising close to the esophageal-gastric junction which are not related to H. pylori and associated inflammation, but in most Asian populations these appear to be very rare. Therefore preventive efforts, and particularly screening, should be focused on markers of bacterial infection, with avoidance of unnecessary exposure to X-ray radiation.

To clarify host and environmental factors for gastric carcinogenesis, we obtained information about gastric cancer mortality in Babol, in the North of Iran, and recruited 130 participants aged 30-80 years from the general population of Babol in 2004. A urea breath test, assessment of IgG antibodies to Helicobacter pylori, a pepsinogen test, a marker of chronic atrophic gastritis, and determination of urinary excretions of sodium and potassium were performed. Diet and lifestyle information was also obtained using a questionnaire. The stomach cancer mortality rate for men in Babol (38.2/10 5 ) was found to be somewhat lower than that for Japanese men (45.1 /10 5 ), while the mortality for women (26.9/10 5 ) was higher than for Japanese women (20.9/10 5 ). Positive rates for the urea breath test were 77.5 and 81.8% for Iranian men and women, respectively. Helicobacter pylori IgG antibodies were present in 68.7 and 73.7% of Iranian men and women, respectively, both values being marginally higher than for Japanese. We also found 51.0 and 52.8% to be positive for a pepsinogen test, significantly higher than the Japanese values. Urinary excretions of salt and potassium in this population appeared approximately the same as the consumption in Japanese. The elevated gastric cancer mortality in both men and women in Babol seems, by and large, to be related to higher H. pylori infection rates and prevalence of chronic atrophic gastritis. Certain factors, including H. pylori DNA diversity, host factors and their interactions, together with the level of medical practice, prevalence of and access to secondary prevention of stomach cancer, may also be associated with the relatively high mortality.

The gastric cancer incidence in Semarang, Indonesia, is exceedingly low: only approximately 1/100th of the level in Japan. To elucidate the reason, we carried out an ecological study recruiting 69 male and 102 female participants from the general populace in January 2005. Positive urea breath tests were 0% for both men and women, and Helicobacter pylori (H. pylori) IgG antibodies were found in 2% (0–5, 95% confidence interval) of men and 2% (0–4) of women, significantly lower than the 62% (58–65) and 57% (53–60), respectively, in Japan. Furthermore, there were no positive findings with the pepsinogen tests in Semarang, again significant in comparison with the 23% (22–25) and 22% (20–23) in Japan. Variation in smoking levels and consumption of NaCl, vegetables and fruit were found, but not to an extent that would allow explanation of the major differences in gastric cancer incidence. We may conclude that the very low prevalence of H. pylori infection and thus chronic atrophic gastritis account for the rarity of stomach cancer in Semarang, Indonesia. (Cancer Sci 2005; 96: 873–875)

conceivably 100% attributable to H. pylori infection, acting in combination with other environmental/behavioral/lifestyle factors [1,9]. Accordingly, we feel that more stress should be placed on categorizing stomach cancer as one of the infection-related malignancies. Prevention of H. pylori infection and eradication measures appear to be crucial for the prevention and control of noncardia gastric cancer.

factors for cardia andnoncardia stomach and esophageal cancer from EPIC-EURO-GAST, a large prospective study. Vegetable intake was foundto be related to a lowered risk of intestinal type gastric cancerand adenocarcinoma of the esophagus, and citrus fruit con-sumption appeared to have a role in protection against cardiagastric cancer and adenocarcinoma of the esophagus.