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This study investigated microplastic distribution characteristics by collecting surface seawater from sea areas to the south of Jeju Island in August 2020. The average microplastic abundance was 0.46 ± 0.27 particles/L (n = 23), and PE had a high ratio, averaging 53%. The levels of fragments and fibers were observed to be 69% and 31% on average, respectively. The most common size of the microplastics was on average 0.02–0.30 mm at a level of 69%. We found a higher abundance of microplastics in the study area than in other open waters such as the Arctic Central Basin and the Atlantic Ocean, whereas the abundance was lower than that in previous studies on coastal areas. We studied an area of open sea connecting China, Japan, and the Pacific Ocean, and, in this region, the microplastic distribution varies depending on sea currents in the surrounding areas. In the summer, the western and central regions of the study sea area have low salinity levels due to discharge from China’s Yangtze River. This generally indicates that high-density plastic deposits are found in the Yangtze River estuary, and low-density plastics are found in the study area. Furthermore, this implies that low- and high-density plastics are transported in water for long periods of time due to the Taiwan Warm Current and because the eastern sea area has high salinity.

Background: A temporary increase in the occurrence of cerebrovascular diseases (CVDs) after the Great East Japan Earthquake and Tsunami of 2011 was reported; however, no studies have been conducted to investigate long-term effects. We assessed the long-term impact of the disaster on the incidence of CVDs. Methods: Incidence data for CVDs from 2008 to 2017 were acquired from the population-based Stroke Registry with an inventory survey of Iwate Prefecture, Japan. Part of the coastal area in Iwate Prefecture was mildly flooded and the other part was severely flooded. Age-adjusted incidence rates of CVDs (according to the Japanese standard population) were calculated for each area. The relative risk (RR) of incidence based on the years before the disaster (2008–2010), adjusted by stratified age groups, was calculated for the year of the disaster (2011), and the years after the disaster (2012–2017) in each area. Results: The age-adjusted incidence rates gradually decreased in all areas, with the exception of a temporary increase among men who lived on the coast the year the disaster occurred. The adjusted RR in the disaster year were not significant in any area and those of the postdisaster years were 0.91 (95% CI 0.87–0.96) for all inland men, 0.93 (0.89–0.97) for all inland women, 0.85 (0.78–0.93) for all coastal men, 0.87 (0.81–0.94) for all coastal women, 0.88 (0.80–0.98) for men at mildly flooded coast, 0.82 (0.75–0.89) for women at mildly flooded coast, 0.79 (0.68–0.91) for men at severely flooded coast, and 0.98 (0.86–1.11) for women at severely flooded coast. Conclusions: The occurrence of CVDs in the flooded coastal areas did not increase in the year of the Great East Japan Earthquake and Tsunami; furthermore, it decreased for men according to the severity of flood damage in the subsequent years; this can be attributed to supportive activities for the tsunami victims and the migration of the population.

Mercury (Hg), cadmium (Cd), and lead (Pb) concentrations in marketed cigarettes from South Korea, Vietnam, Japan, Indonesia, Taiwan, Thailand, the United Kingdom (UK), Belgium, Italy, Finland, and France were investigated. The cigarettes from Vietnam and Thailand had the highest trend of Hg. Meanwhile, Cd was found higher in cigarettes from Thailand, the UK, and Belgium. Pb concentrations in cigarettes from Belgium, the UK, and Korea were higher than others. The average of these heavy metals concentrated in cigarettes was in the order of Pb > Cd > Hg. Furthermore, the contents of these heavy metals in cigarette leaves were much higher than in filter and rolling paper. There was a significant positive correlation between Hg and Cd, but no correlation between Cd and Pb and between Hg and Pb. Significant positive correlations of nicotine with Hg and Cd but not Pb in the cigarette were observed. Activated carbon filters (Ce-C) absorb Cd and Pb from cigarette leaves and rolling paper indicated a higher trapping trend than cellulose acetate filter without activated carbon (Ce). The trapping ratios of Ce-C (Cd: 5.53%, Pb:5.41%) were higher than Ce (Cd:3.09%, Pb:5.49%). On the other hand, Hg had lower absorption by both types of filters (Ce:0.15%, Ce-C:0.02%). This revealed that Hg, Cd and Pb absorption ability by both filters was relatively lower to the total concentration of these metals in tobacco leaves and rolling paper. The concern was that the higher concentrations of metals such as Hg, Cd and Pb in cigarettes might exist in mainstream smoke.

Background and Purpose: High blood pressure increases bleeding risk during treatment with antithrombotic medication. The association between blood pressure levels and the risk of recurrent stroke during long-term secondary stroke prevention with thienopyridines (particularly prasugrel) has not been well studied. Methods: This was a post hoc analysis of the randomized, double-blind, multicenter PRASTRO-I trial (Comparison of Prasugrel and Clopidogrel in Japanese Patients With Ischemic Stroke-I). Patients with noncardioembolic stroke were randomly assigned (1:1) to receive prasugrel 3.75 mg/day or clopidogrel 75 mg/day for 96 to 104 weeks. Risks of any ischemic or hemorrhagic stroke, combined ischemic events, and combined bleeding events were determined based on the mean level and visit-to-visit variability, including successive variation, of systolic blood pressure (SBP) throughout the observational period. These risks were also compared between quartiles of mean SBP level and successive variation of SBP. Results: A total of 3747 patients (age 62.1±8.5 years, 797 women), with a median average SBP level during the observational period of 132.5 mm Hg, were studied. All the risks of any stroke (146 events; hazard ratio, 1.318 [95% CI, 1.094–1.583] per 10-mm Hg increase), ischemic stroke (133 events, 1.219 [1.010–1.466]), hemorrhagic stroke (13 events, 3.247 [1.660–6.296]), ischemic events (142 events, 1.219 [1.020–1.466]), and bleeding events (47 events, 1.629 [1.172–2.261]) correlated with increasing mean SBP overall. Similarly, an increased risk of these events correlated with increasing successive variation of SBP (hazard ratio, 3.078 [95% CI, 2.220–4.225] per 10-mm Hg increase; 3.051 [2.179–4.262]; 3.276 [1.172–9.092]; 2.865 [2.042–4.011]; 2.764 [1.524–5.016], respectively). Event rates did not differ between the clopidogrel and prasugrel groups within each quartile of SBP or successive variation of SBP. Conclusions: Both high mean SBP level and high visit-to-visit variability in SBP were significantly associated with the risk of recurrent stroke during long-term medication with either prasugrel or clopidogrel after stroke. Control of hypertension would be important regardless of the type of antiplatelet drugs. Registration: URL: https://www.clinicaltrials.jp ; Unique identifier: JapicCTI-111582.

Objectives The risk factors that contribute to future functional disability after heart failure (HF) are poorly understood. The aim of this study was to determine potential risk factors to future functional disability after HF in the general older adult population in Japan. Methods The subjects who were community-dwelling older adults aged 65 or older without a history of cardiovascular diseases and functional disability were followed in this prospective study for 11 years. Two case groups were determined from the 4,644 subjects: no long-term care insurance (LTCI) after HF (n = 52) and LTCI after HF (n = 44). We selected the controls by randomly matching each case of HF with three of the remaining 4,548 subjects who were event-free during the period: those with no LTCI and no HF with age +/-1 years and of the same sex, control for the no LTCI after HF group (n = 156), and control for the LTCI after HF group (n = 132). HF was diagnosed according to the Framingham diagnostic criteria. Individuals with a functional disability were those who had been newly certified by the LTCI during the observation period. Objective data including blood samples and several socioeconomic items in the baseline survey were assessed using a self-reported questionnaire. Results Significantly associated risk factors were lower educational levels (odds ratio (OR) [95% confidence interval (CI)]: 3.72 [1.63–8.48]) in the LTCI after HF group and hypertension (2.20 [1.10–4.43]) in no LTCI after HF group. Regular alcohol consumption and unmarried status were marginally significantly associated with LTCI after HF (OR [95% CI]; drinker = 2.69 [0.95–7.66]; P = 0.063; unmarried status = 2.54 [0.91–7.15]; P = 0.076). Conclusion Preventive measures must be taken to protect older adults with unfavorable social factors from disability after HF via a multidisciplinary approach.

Mercury (Hg) is one of the most harmful metals and has been a public health concern according to the World Health Organization (WHO). Artisanal and small-scale gold mining (ASGM) is the world’s fastest-growing source of Hg and can release Hg into the atmosphere, hydrosphere, and geosphere. Hg has been widely used in ASGM industries throughout Southeast Asia countries, including Cambodia, Indonesia, Laos, Malaysia, Myanmar, the Philippines, and Thailand. Here, 16 relevant studies were systematically searched by performing the PRISMA flow, combining the keywords of “Hg”, “ASGM”, and relevant study areas. Mercury concentrations exceeding the WHO and United States Environmental Protection Agency guideline values were reported in environmental (i.e., air, water, and soil) and biomonitoring samples (i.e., plants, fish, and human hair). ASGM-related health risks to miners and nonminers, specifically in Indonesia, the Philippines, and Myanmar, were also assessed. The findings indicated severe Hg contamination around the ASGM process, specifically the gold-amalgamation stage, was significantly high. To one point, Hg atmospheric concentrations from all observed studies was shown to be extremely high in the vicinity of gold operating areas. Attentions should be given regarding the public health concern, specifically for the vulnerable groups such as adults, pregnant women, and children who live near the ASGM activity. This review summarizes the effects of Hg in Myanmar and other Southeast Asian countries. In the future, more research and assessment will be required to investigate the current and evolving situation in ASGM communities.

In this study, we determined the concentration of equine estrogens, such as equilin (Eq) and equilenin (Eqn), in the river water collected from nine research stations in Hokkaido, Japan. The LC–MS/MS analysis revealed that Eq concentrations were 2.7 ± 6.7, 0.22 ± 0.12, and 1.2 ± 0.64 ng/L in Sep 2015, Feb 2016, and Jul 2016, respectively. Eqn had concentration levels similar to those of Eq. Comparison of the concentrations at nine research stations showed that seasonal variation was observed in the detected Eq and Eqn concentration levels. This study was the first to show the occurrences and seasonal variation of Eq and Eqn in the river water of Japan. We further investigated the reproductive and transgenerational effects of Eq in Japanese medaka (Oryzias latipes) exposed to 10, 100, and 1000 ng/L for 21 days and assessed the transcriptional profiles of the estrogen-responsive genes in the livers of both sexes. The reproduction assay demonstrated that 1000 ng/L of Eq adversely affected the reproduction (i.e. fecundity) in the F0 generation and that the hatching of F1 generation fertilized eggs was reduced in the 100 and 1000 ng/L treatment groups. Our qRT-PCR assay revealed that the mRNA expression levels of hepatic vitellogenin 1 and 2, choriogenin L and H, and estrogen receptor α were significantly up-regulated in males exposed to 100 and/or 1000 ng/L of Eq. In contrast, the transcriptional levels of several genes, such as pregnane X receptor and cytochrome P450 3A, were down-regulated in the livers of males after the 21-d exposure. These results suggest that Eq has endocrine-disrupting potential such as reproductive and transgenerational effects by the modulation of hepatic estrogen-responsive genes expression on medaka.

BACKGROUND The appearance of left ventricular hypertrophy on 12-lead electrocardiography (ECG-LVH) has been clarified to be associated with the risk of incidence of cardiovascular events (CVEs) in hypertensive individuals and the general population, but not enough in non-hypertensive individuals. METHODS A total of 4,927 non-hypertensive individuals ≥40 years of age who were free of CVE in the general population were followed for the incidence of CVE. ECG-LVH was defined according to criteria of the Sokolow-Lyon (SL) voltage, Cornell voltage (CV), or Cornell voltage product (CP). RESULTS During the average 9.8 ± 2.0 years of follow-up, 267 individuals (5.4%) had their first CVE. The hazard ratio (HR) for the incidence of CVE after full adjustment by potential confounders significantly increased in the individuals with ECG-LVH by any criteria of the SL voltage, CV, and CP (HR = 1.77, P < 0.001) compared to those with no ECG-LVH. This association was also significant in individuals without any of obesity, dyslipidemia, and diabetes mellitus or those with systolic blood pressure (BP) CONCLUSIONS In the absence of hypertension, ECG-LVH parameters are associated with the increased risk of developed CVEs independent of the established risk factors and provide the additional prognostic value in an assessment of the CVE risk using the traditional risk factors.

Diabetes mellitus is characterized by alterations in blood glucose (BG) metabolism, and glycated hemoglobin (HbA1c) has been widely used as a marker of the BG concentration. Diabetes often coexists with high blood pressure (BP). High BP and hyperglycemia are well-known risk factors of stroke. We examined the extent to which the increased risk of stroke in diabetic individuals is attributable to BP and BG using prospectively collected data from the Japanese general population. During an average 8.3 ± 2.2 years of follow-up, out 1606 diabetic individuals aged ≥40 years who were free of cardiovascular disease, 119 participants (7.4%) developed stroke. In multivariable analysis, a significant difference in the risk of incident stroke was noted among the BP categories, including normotension (BP1), prehypertension (BP2), and hypertension (BP3; P for trend = 0.001). By contrast, no difference was noted among the BG categories, including HbA1c levels

Total mercury (THg) and methylmercury (MeHg) bioaccumulation was explored in the Bimastus parvus species of earthworm (B. parvus) native to the leachate-contaminated forest soils around a Hg-polluted traditional landfill in Japan. General soil properties and concentrations of THg and MeHg in forest soils and in B. parvus were determined. The results indicated that the average THg concentrations in B. parvus and in forest soils in the leachate-contaminated sites were 10.21 and 14.90 times higher than those in the reference sites, respectively, whereas similar average MeHg concentrations were observed in forest soils (< 0.01 mg kg-1) and in B. parvus (0.100-0.114 mg kg-1) across all sampled sites. The average bioaccumulation factors of THg in B. parvus (BAFTHg) in forest soil were similar between the leachate-contaminated sites and the reference sites. Cluster and regression analyses demonstrated that the B. parvus Hg (THg and MeHg) and soil THg were positively correlated with each other and with soil organic matter (SOM) and clays, but were negatively correlated with sand and hardly correlated with silts and pH in leachate-contaminated forest soils. From these results, it was proposed that Hg exposure to food chains is possible through B. parvus, because B. parvus showed a high ability to accumulate THg and MeHg in both leachate-contaminated and reference forest soils. Together, these findings indicated that the role of B. parvus in MeHg production is not clear, and it is possible that the MeHg in B. parvus was firstly formed within forest soils and then accumulated in their tissues.

Background The relative and absolute risks of stroke and heart failure attributable to atrial fibrillation (AF) have not been sufficiently examined. Methods A prospective study of 23,731 community-dwelling Japanese individuals was conducted. Participants were divided into two groups based on the presence or absence of prevalent AF (n = 338 and n = 23,393, respectively). Excess events (EE) due to AF and relative risks (RRs) determined using the non-AF group as the reference for incident stroke and heart failure were estimated using Poisson regression stratified by age groups (middle-aged: 40–69 years old; elderly: 70 years of age or older) after adjustment for sex and age. Results There were 611 cases of stroke and 98 cases of heart failure during the observation period (131,088 person-years). AF contributed to a higher risk of stroke both in middle-aged individuals (EE 10.4 per 1000 person-years; RR 4.88; 95% confidence interval [CI], 2.88–8.29) and elderly individuals (EE 18.3 per 1000 person-years; RR 3.05; 95% CI, 2.05–4.54). AF also contributed to a higher risk of heart failure in middle-aged individuals (EE 3.7 per 1000 person-years; RR 8.18; 95% CI, 2.41–27.8) and elderly individuals (EE 15.4 per 1000 person-years; RR 7.82; 95% CI, 4.11–14.9). Results obtained from multivariate-adjusted analysis were similar (stroke: EE 8.9 per 1000 person-years; RR 4.40; 95% CI, 2.57–7.55 in middle-aged and EE 17.4 per 1000 person-years; RR 2.97; 95% CI, 1.99–4.43 in elderly individuals; heart failure: EE 3.1 per 1000 person-years; RR 7.22; 95% CI, 2.06–25.3 in middle-aged and EE 14.1 per 1000 person-years; RR 7.41; 95% CI, 3.86–14.2 in elderly individuals). Conclusions AF increased the risk of stroke by the same magnitude as that reported previously in Western countries. AF increased the RR of heart failure more than that in Western populations., Highlights • Incidence rates for stroke and HF were estimated in Japanese community dwellers. • Subjects were divided into AF and non-AF groups separately by age (40–69 and ≥70). • AF increased the risk of stroke by the same magnitude as in Western populations. • AF increased the risk of HF more than that in Western populations. • The absolute risk differences of outcomes were larger in the elderly individuals.

Background: Cerebrovascular diseases are a major cause of death for Japanese people, but up-to-date national or prefectural incidences are unknown. We calculated the last 10-year cerebrovascular diseases incidence in an aging local prefecture in Japan with 1.2 million inhabitants and used the data to predict the future incidence. Methods: We retrospectively analyzed inventory surveys from the Iwate Stroke Registry (data from the whole Iwate Prefecture) from 2008 to 2017. We compared age-adjusted and age-specific incidence rates between the first half period from 2008 to 2012 and the last half period from 2013 to 2017. We used the incidence change rate and the forecasted population number to predict the future incidence. Results: In a decade, the age-adjusted cerebrovascular diseases incidence rate per 100,000 person-years in the Japan standard population decreased from 212.1 to 176.8 in men and from 123.1 to 97.0 in women. The age-specific incidence rates and the number of incidences of those younger than 55 years decreased only slightly, but those of people 55 years or older decreased. The total number of incidence in 2040 will decrease to two-thirds of the value in 2015, but the number of incidence of those 85 years and older will increase by 2040. Conclusions: The cerebrovascular diseases rate and number of incidence decreased during the last decade and will decrease in the future, but the incidence in the oldest-old will increase. Specific nursing care and social measures to treat cerebrovascular diseases in the oldest-old will be needed.

Introduction: Previous studies have indicated that the female gender is one of the important risk factors for disability after stroke; however, most studies have been conducted in Western countries, and the higher risk of disability after stroke observed in women is thought to be different in Japan, where the proportion of hemorrhagic stroke (HS) is relatively higher than that in Western countries. Hypothesis: We assessed the hypothesis that the higher risk of disability after stroke attributable to the female gender was different between ischemic stroke (IS) and HS. Methods: We used 10-year community-based cohort data of 8,698 participants aged 65 years or older without cardiovascular disease or long-term care insurance (LTCI) at the time of the baseline survey. The stroke incidence was confirmed by reviewing the Iwate Stroke Registry. Functional disability was defined as being newly certified by the LTCI system. Participants were classified into three groups: G1, event-free (no stroke and no disability, n=7,950); G2, no disability after stroke (IS=177, HS=55); and G3, disability after stroke (IS=346, HS=170). Multivariate-adjusted odds ratios (ORs) of the female gender in G2 and G3 (reference: G1) were calculated using multinomial logistic regression with adjustments for age, hypertension, diabetes, dyslipidemia, overweight, current smoking, regular alcohol consumption, and regular exercise separately in those with IS and HS. Results: The ORs of the female gender were not high in G3 in IS, while the OR (95% confidence interval) was significantly high in G3 (1.55 (1.03-2.34)) in HS (see table). Conclusions: The proportion of females in the subjects with disabilities after HS was significantly higher than the proportion of males after multivariate adjustment. This suggested that the female gender was a significant risk factor for disability after HS, but not after IS in Japanese community-dwelling individuals.

Total mercury (THg) and methylmercury (MeHg) bioaccumulation was explored in the Bimastus parvus species of earthworm (B. parvus) native to the leachate-contaminated forest soils around a Hg-polluted traditional landfill in Japan. General soil properties and concentrations of THg and MeHg in forest soils and in B. parvus were determined. The results indicated that the average THg concentrations in B. parvus and in forest soils in the leachate-contaminated sites were 10.21 and 14.90 times higher than those in the reference sites, respectively, whereas similar average MeHg concentrations were observed in forest soils (0.01 mg kg

This study aimed to develop a simpler method for determining total mercury (T-Hg) and methylmercury (MeHg) in biological samples by using methyl isobutyl ketone (MIBK) in the degreasing step. The fat in the samples was extracted by MIBK to the upper phase. T-Hg transferred into the water phase. This was followed by the extraction of MeHg from the water phase using HBr, CuCl2 and toluene. The MeHg fraction was reverse-extracted into L-cysteine-sodium acetate solution from toluene. The concentrations of T-Hg and MeHg were determined by heating vaporization atomic absorption spectrometry. Certified reference materials for T-Hg and MeHg in hair and fish were accurately measured using this method. This method was then applied to determine T-Hg and MeHg concentrations in the muscle, liver and gonads of seafood for the risk assessment of MeHg exposure. The mean T-Hg and MeHg concentrations in squid eggs were 0.023 and 0.022 µg/g, and in squid nidamental glands 0.052 and 0.049 µg/g, respectively. The MeHg/T-Hg ratios in the eggs and nidamental glands of squid were 94.4% and 96.5%, respectively. The mean T-Hg and MeHg concentrations in the gonads of sea urchins were 0.043 and 0.001 µg/g, respectively, with a MeHg/T-Hg ratio of 3.5%. We developed an efficient analytical method for T-Hg and MeHg using MIBK in the degreasing step. The new information on MeHg concentration and MeHg/T-Hg ratios in the egg or nidamental glands of squid and gonads of sea urchin will also be useful for risk assessment of mercury in seafood.

BACKGROUND The ability of cardiovascular biomarkers to predict the incidence of stroke subtypes remains ill-defined in the general population.Methods and Results:The blood levels of B-type natriuretic peptide (BNP) and high-sensitivity C-reactive protein (hs-CRP) and urinary albumin corrected by urinary creatinine (UACR) were determined in a general population (n=13,575). The ability to predict the incidence of ischemic stroke subtypes (lacunar, atherothrombotic, cardioembolic) for each biomarker was assessed based on the area under the receiver-operating characteristic curve (AUC-ROC) and using Cox proportional hazard modeling. The predictive abilities of UACR and hs-CRP for any subtype of ischemic event were found to be suboptimal. However, the ability of BNP to predict the incidence of cardioembolic stroke was excellent (AUC-ROC=0.81). When BNP was added to established stroke risk factors, the ability to predict cardioembolic stroke in terms of the AUC-ROC significantly improved (4-year follow-up, P=0.018; 8-year follow-up, P=0.009). Furthermore, when BNP was added to the JPHC score, the ability to predict cardioembolic stroke was significantly improved (net reclassification improvement=0.968, P

People are exposed to methylmercury (MeHg) mainly through fish consumption, which is increasing in Vietnam. However, little information is available on estimating the health risk of MeHg exposure through fish consumption in Vietnam. The present study examined the association between mercury (Hg) levels in hair and selenium (Se) levels in toenails of 196 Vietnamese people and their fish consumption, using a dietary questionnaire to obtain information pertinent for assessing health risk owing to MeHg exposure. The geometric mean of Hg levels in the hair of males and females was 617 ng/g and 575 ng/g, respectively. We found that Hg levels in the hair of 98% of the Vietnamese study subjects were lower than the provisional tolerable weekly intake for MeHg (1.6 µg Hg/kg body weight; which is equivalent to a hair Hg concentration of approximately 2,300 ng/g, with an uncertainty factor of 6.4). There were significant differences in the age-adjusted geometric mean of Hg levels found in hair from females related to their frequency of freshwater fish consumption. The levels of Hg in hair and Se in toenails increased with an increased frequency of marine fish consumption, and both showed a significant positive correlation in subjects who consumed marine fish ≥ once/week. This is the first cross-sectional study to investigate the association between hair Hg levels and fish consumption in Vietnam. These findings provide valuable information for future assessments of the health risk of MeHg exposure through fish consumption in Vietnam.

Background: Smoking is an important risk factor for cardiovascular disease, however, to what extent smoking increases excessive deaths and strokes in a general population has not been sufficiently examined especially in women. Methods: A total of 10,382 female and male participants aged 65 years or older were divided into two groups according to smoking status (current smoker; never smoker). Past smokers were excluded. Main outcomes were all-cause death and incident stroke. Age-adjusted mortality and incidence rates were estimated in the groups using Poisson’s regression analysis. Age-adjusted rate ratios (RR) and excess events (EE per 1000 person-years) attributable to smoking were determined using the rate in never smokers as a reference. Results: There were 1410 deaths and 735 strokes during the 9.0-year observation period (90,099 person-years). Smoking contributed to a 2.3-fold higher risk of death in women and 1.8-fold higher risk in men. It contributed to 12 excess deaths per 1000 person-years in both men and women. The rate ratio and excessive events of stroke were likely to be higher in women than those in men (RR: 2.6 vs. 1.6; EE: 9.3 vs 5.0, see table). Conclusion: Smoking significantly increases risks of death and stroke not only in men but also in women. Absolute risk difference of stroke attributable to smoking is likely to be larger in women than in men.

Background Using data from a large-scale community-based Japanese population, we attempted to identify factors associated with tooth loss in middle-aged and elderly men. Methods A total of 8352 men aged 40 to 79 years who lived in the north of the main island of Japan and underwent health checkups were enrolled between 2002 and 2005. Number of teeth was assessed by the question, “How many teeth do you have (0, 1–9, 10–19, or ≥20)?”. On the basis of the answer to this question, participants were classified into 2 groups (≤19 teeth or ≥20 teeth). Using multivariate logistic regression, factors related to having 19 or fewer teeth were estimated. Results The numbers (percentages) of participants who had 0, 1 to 9, 10 to 19, and 20 or more teeth were 1764 (21.1%), 1779 (21.3%), 1836 (22.0%), and 2973 (35.6%), respectively. Among the participants overall and those aged 65 to 79 years, having 19 or fewer teeth was significantly associated with older age, smoking status (current smoking and ex-smoking), and low education level. In addition, men with 19 or fewer teeth were more likely to have a low body mass index and low serum albumin level and less likely to be current alcohol drinkers. Among men aged 40 to 64 years, but not men aged 65 to 79 years, those with 19 or fewer teeth were more likely to have a low serum high-density lipoprotein cholesterol level and high glycosylated hemoglobin (HbA1c) level. Conclusions Smoking, low education level, and poor nutritional status were associated with tooth loss among middle-aged and elderly Japanese men.

【目的】頸動脈プラークに対する抗血小板薬の適応とその効果に関する報告はさまざまで確立されたものがない．今回われわれは，頸動脈病変を有する症例に対して，血管内皮機能改善作用を持つ抗血小板薬(シロスタゾール)を投与し，プラークの体積および形態の変化を三次元(3D)超音波検査法により経時的に測定し，その治療効果を脂質代謝の面から検討した．【対象】頸動脈プラークを有し，過去6カ月以上内服薬の変更のない脳梗塞患者21症例(男性16例，女性5例，年齢67±7歳)．【方法】シロスタゾール200 mg/日を経口投与し，治療前および治療3カ月後に3D頸動脈超音波検査を施行して，プラーク体積とその形態学的な変化を観察した．同時にシロスタゾール投与前後の血液生化学データの比較検討を行った．頸動脈超音波検査は，3D超音波測定装置：VOLUSON 730 EXPERT，3D4D probe(GE Healthcare)を用いた．【結果】シロスタゾール投与3カ月後にプラークの体積は0.44±0.39 cm3から0.39±0.40 cm3に退縮傾向を認めた(p=0.005)．このうち，シロスタゾール投与3カ月後にプラーク体積が退縮(15例)または不変(4例)であった19例について検討すると，血清HDL-C値は59±22 mg/dlから65±23 mg/dlに上昇傾向を認めた(p=0.017)．【結論】シロスタゾール投与により，頸動脈プラークの体積は退縮した．これはシロスタゾールの持つ血管内皮機能改善作用に加え，脂質代謝改善作用が関与していることが考えられた．

Seasonal and diurnal fluctuations in pharmaceuticals and personal care products (PPCPs) concentrations in residential sewage water were ascertained in an area with no businesses industry (e.g., plants or offices) upstream. PPCPs with high detection rates included ibuprofen, acetaminophen and indomethacin (antipyretic analgesics), atenolol and disopyramide (antiarrhythmics), clarithromycin (antibiotic), levofloxacin (synthetic antimicrobial agent) and triclosan (disinfectant). In summer, the concentration of triclosan was the highest, while in winter, the concentrations of ibuprofen and acetaminophen were higher than the others. Moreover, three types of diurnal fluctuations were observed: no marked diurnal changes (triclosan), high daytime concentrations (disopyramide) and high nighttime concentrations (acetaminophen)., Journal of Health Science, 54(2), pp.240-243; 2008

Ferritic stainless steels such as Fe-2.25Cr-1Mo-1Zr, Fe-25Cr-1Zr and Fe-13Cr-8Ni-2Mo-1Zr with ultra-fine grain size of 0.2μm were prepared by hot extrusion after mechanical alloying. Axial fatigue life tests for plane round bar specimens of these steels were conducted at 473K. The higher fatigue strengths of these steels at 473K were observed as compared with those of conventional steels such as SAE8740 and SNB16. Fatigue strength expressed as maximum stress at 3 × 106 cycles for Fe-2.25Cr-1Mo-1Zr, Fe-13Cr-8Ni-2Mo-1Zr and Fe-25Cr-1Zr were 1150, 1150 and 1350MPa, respectively. Transranular fracture surfaces were predominantly observed at crack initiation and propagation area. Striation was observed at defined region of crack propagation area. It can be concluded that the higher fatigue strength of ferritic stainless steels with ultra-fine grain size of 0.2μm is strongly governed by delay of crack initiation.

Background While it is assumed that dialysis patients in Japan have a higher prevalence of atrial fibrillation (AF) than the general population, the magnitude of this difference is not known. Methods Standardized prevalence ratios (SPRs) for AF in dialysis patients (n = 1510) were calculated compared to data from the general population (n = 26 454) living in the same area. Results The prevalences of AF were 3.8% and 1.6% in dialysis patients and the general population, respectively. In male subjects, these respective values were 4.9% and 3.3%, and in female subjects they were 1.6% and 0.6%. The SPRs for AF were 2.53 (95% confidence interval [CI], 1.88-3.19) in all dialysis patients, 1.80 (95% CI, 1.30-2.29) in male dialysis patients, and 2.13 (95% CI, 0.66-3.61) in female dialysis patients. Conclusions The prevalence of AF in dialysis patients was twice that in the population-based controls. Since AF strongly contributes to a higher risk of cardiovascular mortality and morbidity in the general population, further longitudinal studies should be conducted regarding the risk of several outcomes attributable to AF among Japanese dialysis patients.

Sandhoff disease (SD) is an autosomal recessive GM2 gangliosidosis caused by the defect of lysosomal beta-hexosaminidase (Hex) beta-subunit gene associated with neurosomatic manifestations. Therapeutic effects of Hex subunit gene transduction have been examined on Sandhoff disease model mice (SD mice) produced by the allelic disruption of Hexb gene encoding the murine beta-subunit. We demonstrate here that elimination of GM2 ganglioside (GM2) accumulated in the fibroblastic cell line derived from SD mice (FSD) did not occur when the HEXB gene only was transfected. In contrast, a significant increase in the HexB (betabeta homodimer) activity toward neutral substrates, including GA2 (asialo-GM2) and oligosaccharides carrying the terminal N-acetylglucosamine residues at their non-reducing ends (GlcNAc-oligosaccharides) was observed. Immunoblotting with anti-human HexA (alphabeta heterodimer) serum after native polyacrylamide gel electrophoresis (Native-PAGE) revealed that the human HEXB gene product could hardly form the chimeric HexA through associating with the murine alpha-subunit. However, co-introduction of the HEXA encoding the human alpha-subunit and HEXB genes caused significant corrective effect on the GM2 degradation by producing the human HexA. These results indicate that the recombinant human HexA could interspeciesly associate with the murine GM2 activator protein to degrade GM2 accumulated in the FSD cells. Thus, therapeutic effects of the recombinant human HexA isozyme but not human HEXB gene product could be evaluated by using the SD mice.

We have established spontaneously immortalized Schwann cell lines from dorsal root ganglia and peripheral nerves of Sandhoff mice. One of the cell lines exhibited genetically and biochemically distinct features of Sandhoff Schwann cells. The enzyme activities toward 4-methylumbelliferyl N-acetyl-beta-D-glucosamine (beta-hexosaminidases A, B, and S) and 4-methylumbelliferyl N-acetyl-beta-D-glucosamine-6-sulfate (beta-hexosaminidases A and S) were decreased, and GM2 ganglioside accumulated in lysosomes of the cells. Incorporation of recombinant human beta-hexosaminidase isozymes expressed in Chinese hamster ovary cells into the cultured Sandhoff Schwann cells via cation-independent mannose 6-phosphate receptors was found, and the incorporated beta-hexosaminidase A degraded the accumulated GM2 ganglioside. The established Sandhoff Schwann cell line is useful for investigation and development of therapies for Sandhoff disease.

Sandhoff disease is an autosomal recessive lysosomal storage disease caused by a defect of the beta-subunit gene (HEXB) associated with simultaneous deficiencies of beta-hexosaminidase A (HexA; alphabeta) and B (HexB; betabeta), and excessive accumulation of GM2 ganglioside (GM2) and oligosaccharides with N-acetylglucosamine (GlcNAc) residues at their non-reducing termini. Recent studies have shown the involvement of microglial activation in neuroinflammation and neurodegeneration of this disease. We isolated primary microglial cells from the neonatal brains of Sandhoff disease model mice (SD mice) produced by disruption of the murine Hex beta-subunit gene allele (Hexb-/-). The cells expressed microglial cell-specific ionized calcium binding adaptor molecule 1 (Iba1)-immunoreactivity (IR) and antigen recognized by Ricinus communis agglutinin lectin-120 (RCA120), but not glial fibrillary acidic protein (GFAP)-IR specific for astrocytes. They also demonstrated significant intracellular accumulation of GM2 and GlcNAc-oligosaccharides. We produced a lentiviral vector encoding for the murine Hex beta-subunit and transduced it into the microglia from SD mice with the recombinant lentivirus, causing elimination of the intracellularly accumulated GM2 and GlcNAc-oligosaccharides and secretion of Hex isozyme activities from the transduced SD microglial cells. Recomibinant HexA isozyme isolated from the conditioned medium of a Chinese hamster ovary (CHO) cell line simultaneously expressing the human HEXA (alpha-subunit) and HEXB genes was also found to be incorporated into the SD microglia via cell surface cation-independent mannose 6-phosphate receptor and mannose receptor to degrade the intracellularly accumulated GM2 and GlcNAc-oligosaccharides. These results suggest the therapeutic potential of recombinant lentivirus encoding the murine Hex beta-subunit and the human HexA isozyme (alphabeta heterodimer) for metabolic cross-correction in microglial cells involved in progressive neurodegeneration in SD mice.

Phytoestrogens and organochlorine pesticides in the diet of laboratory animals are a possible source of interference in bioassays that assess estrogenic activity. In the present study, we investigated the levels of dietary phytoestrogens, organochlorine pesticides and the estrogenic activity of various diets for an experimental fish and discuss the potential contribution of these substances to estrogenic activity, in comparison with those used in previous studies. After hydrolysis with β-glucuronidase, genistein and daidzein were detected in all of the diets, and there were no significant differences in the contents of these substances among present and previous investigations. In addition, organochlorine pesticides, such as hexachlorobenzene (HCB), β-benzene hexachloride (β-BHC), γ-BHC, trans-nonachlor, and/or endrin, were detected in most fish diets. All of these diets exhibited higher levels of activation of β estrogen receptors than with α estrogen receptors in an in vitro yeast-based bioassay. These results indicate that phytoestrogens, such as genistein and daidzein, were the main substances contributing to the estrogenic activity of the diet. Moreover, some diets may exert estrogenic activity in in vivo tests, indicating the necessity for more careful selection of the feeding diet and measurement of estrogenic substances when performing routine screening assays for endocrine-disrupting chemicals., Journal of Health Science v.51(2) p.212-219, 2005

Triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether) is widely used as antibacterial agent in various industrial products, such as textile goods, soap, shampoo, liquid toothpaste and cosmetics, and often detected in wastewater effluent. In this study, the effects of TCS on the early life stages and reproduction of medaka (Oryzias latipes) were investigated. The 96-h median lethal concentration value of TCS for 24-h-old larvae was 602 microg/l. The hatchability and time to hatching in fertilized eggs exposed to 313 microg/l TCS for 14 days were significantly decreased and delayed, respectively. An assessment of the effects of a TCS 21-day exposure period on the reproduction of paired medaka showed no significant differences in the number of eggs produced and fertility among the control and 20, 100 and 200 microg/l TCS treatment groups. However, concentrations of hepatic vitellogenin were increased significantly in males treated with TCS at 20 and 100 microg/l. In the F(1) generations, although the hatching of embryos in the 20 microg/l treatment showed adverse effects, there was no dose-response relationship between hatchability and TCS treatment levels. These results suggest that TCS has high toxicity on the early life stages of medaka, and that the metabolite of TCS may be a weak estrogenic compound with the potential to induce vitellogenin in male medaka but with no adverse effect on reproductive success and offspring.

Exposure experiments in medaka and photodecomposition tests were performed using a metabolite of bisphenol A [4-methyl-2,4-bis(p-hydroxyphenyl)-pent-1-ene; MBP], the solubility limit of which is 42 mg/l of water. Three adult medaka were kept in a 2 l glass beaker at 25 ± 1°C for 4 days. The LC50 for 96 hr was > 1000 ppb. The measured average MBP concentration in the breeding water (nominal concentration of 100 ppb) was 49.2 ppb. The average concentration in the whole bodies of medaka after 4 days was 1.92 mg/g-wet body, and the bioconcentration factor (BCF) of MBP was calculated to be 39.0. MBP in water and acetone was decomposed very easily, with about 98% of the MBP being decomposed after several hours under sunlight. MBP was also decomposed after 48 hr of illumination under a white fluorescent lamp., Journal of Health Science v.50(6) p.576-580, 2004

To understand the cause of discoloration of the sea laver "nori," which is found in the Ariake Sea, the concentrations of pigments and elements in the normal and discolored laver samples were determined. In the discolored samples, a decrease in all of the pigments, chlorophyll a and carotenoids, and proteinous pigments, phycobiliproteins, was clearly observed. This was accompanied by a decrease in the content of Fe, Zn, Mn, Cu, and P. Good correlations between these elements and chlorophyll a, as well as between these elements and phycobiliproteins, were confirmed, indicating that, in addition to the deficiency of nitrogen and phosphorus, the deficiency of trace elements (Fe, Zn, Mn, and Cu), which are specifically required for photosynthesis, could be a reason for the discoloration of nori. The cause of elemental deficiency is also discussed.

4,4'-Thiodiphenol (TDP) is a bisphenol derivative, and there has been no report on TDP removal by any plants or pure bacterial cultures. The removal of TDP by Portulaca oleracea cv., a floricultural herbal plant, was examined with a hydroculture system, and 97% of TDP was removed after 4 days culture.

The free-living nematode, Caenorhabditis elegans (C. elegans) was adopted as a multicellular biosensor of biological toxicity from alkylphenols and organotin compounds. Alkylphenols were found to affect reproduction at lower doses than indicated by the acute toxicity assay. In particular, nonylphenol altered the reproduction rate of C. elegans at a dose 10- to 100-fold lower than the 50% lethal concentration (LC50). A comparison of the number of viable worms and eggs suggested that alkylphenols and organotin compounds possess hatching toxicity. A 0.1 μM dose of organotin compounds caused a significant decrease, in the order of 20-50%, in reproduction of the worms, and an abnormal male: hermaphrodite ratio was observed. C. elegans therefore appears to represent a potent and sensitive organism with which to evaluate the biological effects of chemicals. In particular, the sensitivity of reproduction as an endpoint is highly useful for assessing the sublethal effects of chemicals., Journal of Health Science v.48(6) p.555-559, 2002

We describe a novel approach to evaluating the respiratory toxicity of chemicals in the free-living nematode Caenorhabditis elegans. Using DOX-96KT, a general purpose, multi-channel dissolved oxygen (DO) measuring system, we measured the DO concentration in culture media containing C. elegans exposed to chemicals to assay for respiratory toxicity. The current value, which is an index of the dissolved oxygen concentration in culture media, was measured every 10 sec for 30 min at 24°C. We focused on the respiration levels of the exposed worms between 500 and 1800 sec. This method produces results that are similar to the computer tracking system measuring behavioral toxicity. Since it can do multiple dilution series tests at a given time, it is useful for concentration-activity correlation studies. This novel technique is not only an alternative to the computer tracking system for measuring behavioral toxicity but also a rapid sublethal toxicity test for chemical hazard assessment., Journal of Health Science v.48(3) p.269-272, 2002