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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.

Food consumption remains the commonest pathway through which humans ingest higher levels of mercury (Hg). Long-term exposure to Hg through Hg-contaminated food may result in acute or chronic Hg toxicity. Incessant discharge of Hg waste from ASGM facilities into nearby farms contaminates food crops. Ingestion of such food crops by residents may lead to detrimental human health effects. The human health risks upon exposure to total mercury (THg) and methylmercury (MeHg) in farmland soils and plantains from farms sited near ASGM facilities were studied in four communities around Obuasi, Ghana. The human health risk assessment was evaluated using hazard quotient (HQ), estimated average daily intake (e AvDI), hazard index (HI) and Hg elimination and retention kinetics. Tweapease, Nyamebekyere and Ahansonyewodea had HQ, e AvDI and HI for THg of plantains for both adults and children below the recommended USEPA limit of 1, 3 × 10-4 mg/kg/day and 1, respectively. Odumase had HQ, e AvDI and HI for THg of plantains for both adults and children, higher than the guideline values. This meant that only Odumase may cause non-carcinogenic human health effects upon repeated exposure. The HQ, e AvDI and HI values of MeHg for all the study areas were far below guideline values, hence may not pose any non-carcinogenic human health risks to residents even upon repeated exposure. Retention and elimination kinetics of Hg also showed that only plantains from Odumase may pose significant non-carcinogenic human health risks to residents because the final amount of inorganic mercury exceeded the extrapolated USEPA guideline value of 0.393 μg/kg/year.

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.

BACKGROUND Left ventricular hypertrophy (LVH) is a common predictor of the cardiovascular prognosis in chronic kidney disease (CKD). However, whether or not electrocardiography-derived LVH (ECG-LVH) has prognostic value in patients with various degrees of CKD and improves the cardiovascular risk stratification based on traditional risk factors remains unclear. METHODS A total of 7206 participants at least 40 years of age who were free from cardiovascular events in a general population were followed for the incidence of cardiovascular events. CKD was confirmed by either the presence of a reduced estimated glomerular filtration rate (eGFR) (

Equine estrogens (EQs) are steroidal hormones isolated from the urine of pregnant mares and are used in the formulation of human medications. This study initially investigated the embryonic developmental toxicity of equilin (Eq) and equilenin (Eqn) in medaka (Oryzias latipes). Malformations were observed in embryos exposed to nominal concentrations of 1 and 10 mg/L of Eq and Eqn. Delayed hatching was observed at 1 mg/L of Eq. To further investigate the molecular mechanism of developmental toxicity caused by Eq and Eqn, transcriptome and bioinformatics analyses were performed. Among 2016 and 3855 total differentially expressed genes (DEGs), 1117 DEGs overlapped between Eq. (55.4 % of total DEGs) and Eq. (29.0 % of total DEGs). Gene ontology indicated effects in terms related to blood circulation and cell junctions. Pathway analyses using DEGs revealed that both Eq and Eqn treatments at 10 mg/L affected various KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, such as neuroactive ligand-receptor interaction, mitogen-activated protein kinase signaling, retinol metabolism, and cytokine-cytokine receptor interaction. These results suggest that the disruption of these KEGG pathways is involved in the developmental toxicity of EQs in medaka embryos.

The removal of Hg from solid waste plays a key role in environmental protection. In this study, a fast, simple, and effective method for the removal of Hg by acid extraction, using a combination of vortex agitation and ultrasonic irradiation along with hydrobromic acid (HBr), was established using Hg-containing solid wastes. The optimal durations of vortex agitation and ultrasonic irradiation with 48% v/v of HBr were 5 and 6 min, respectively, and total Hg (T-Hg) extraction was achieved within 21 min. The proposed method was validated using the Certified Reference Material (CRM) ERM CC580 (estuarine sediment) and CRM NMIJ 7302-a (marine sediment). Under the optimized conditions, the efficiency rates of T-Hg extraction in both CRMs were 99.5% and 94.2%, with repeatabilities of 3.21% RSD and 2.31% RSD, respectively. The proposed extraction method can also be used for the remediation of Hg in other environmental matrices.

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.

Frequent discharge of mercury waste from artisanal and small-scale gold mining (ASGM) facilities into nearby farms may contaminate foodstuffs and the entire farms. High contamination levels may result in ecological risks to the soil, plants, animals, humans, and the entire farm ecosystem. This original research is the first study within the catchment areas that describes the effects of mercury waste on the entire farm ecosystem. In this study, the contamination levels and the associated ecological risks of farmland soils, plantains, and cassavas from farms sited near ASGM facilities in four communities around Obuasi, Ghana, were evaluated using the Hakanson (1980) model. Results showed that all samples except for the edible parts of plantains from Tweapease, Nyamebekyere, and Ahansonyewodea and plantain peels from Nyamebekyere and Ahansonyewodea were contaminated and may pose moderate to very high ecological risks. All farms were also contaminated and may pose considerable to very high ecological risks. The farms at Odumase were the highest contaminated with degree of contamination (C

Urban dust has been contaminated with toxic heavy metals from various diffused sources. On August 28, 2019, the compact fluorescence lamp (CFL) factory that generates light for Rang Dong Light Source and Vacuum Flask in Hanoi City in Vietnam was accidentally fired. The assessment for Hg contamination and its human health impact 2 months after the incident was conducted in autumn 2019. The heavy Hg pollution is still found near CFL. Additionally, localized Hg pollution by air and wind direction was identified at sites in the northeast direction from CFL. Namely, in the area located downstream of the southwest monsoon wind, Hg had a trend higher than other directions. The hazard quotient (HQ) and the hazard index (HI) were evaluated by four routes of Hg exposure pathways. The HI values for children and adults in the most polluted site (Site 15) were 0.968 and 0.468, respectively. This meant that children who lived around this site and commuted to schools were the most at risk regarding the potential adverse health effects of Hg in street dust around the polluted areas. This study also showed that Hg levels were affected by wind direction and that the higher Hg levels in the most polluted sites resulted from the wind flow to the sites. This study revealed that street dust may be a useful tool for the assessment of human and environmental health.

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.

The contents and spatial distribution of mercury (Hg), including soil-Hg fractionation and Hg-containing native earthworm Bimastos parvus (B. parvus) species, were investigated in the leachate-contaminated zone of a large traditional landfill, Japan. Soil-Hg was fractionated into 5 categories: F1/water soluble Hg (Hg-w), F2/human stomach acid soluble Hg (Hg-h), F3/organic-chelated (Hg-o), F4/elemental Hg (Hg-e), and F5/mercuric sulfide (Hg-s). The total mercury (T-Hg) and methylmercury (MeHg) of native B. parvus, and the geochemical properties of soils were examined in this study. Soil T-Hg concentration ranged between 0.227 and 2.919 mg kg−1 dry weight (dw). The T-Hg and MeHg concentrations of B. parvus species ranged from 1.242 to 6.775 mg kg−1 dw and from 0.031 to 0.218 mg kg−1 dw, respectively. Percentages of soil-Hg fractions were in the order of F3/Hg-o > F4/ Hg-e > F5/Hg-s > F1/Hg-w > F2/Hg-h, and the fractions of Hg-o and Hg-e were 55.50% and 35.31%, respectively. Similar distributions and close correlations between the levels of B. parvus Hg and soil Hg-o, Hg-e, and Hg-s were observed in this study. The distribution of Hg in B. parvus was associated with soil organic matter (SOM) content and particle size (sand, clay); however, it was not correlated with Hg-w or Hg-h. The results indicated that easily bioavailable and soluble Hg fractions (Hg-w, Hg-h) of the soil were not appropriate to illustrate the distribution of Hg in native B. parvus. Instead, the stable soil-Hg fractions (Hg-o, Hg-e, and Hg-s) demonstrated good relationships of spatial distribution with B. parvus Hg in leachate-contaminated soil. It is advisable to preclude the evaluation of Hg biological distribution using soluble Hg fractions only. Stable Hg fractions in leachate-contaminated soil should also be included for assessing the biological distribution of Hg in leachate-contaminated soils.

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 accuracy of a stroke registration program in Iwate prefecture was greatly affected by cooperation from medical facilities and doctors in the field. The number of registered cases from noncore hospitals was less, but the accuracy of registration was unknown. This report presents the impact and effectivity of an inventory survey of the stroke registry. Subjects and Methods Details of subjects living in coastal and northern regions of Iwate Prefecture who developed a cerebrovascular attack between 2012 and 2014 were obtained from the Iwate Stroke Registry through an inventory survey. Annual incidence rate from core hospitals and noncore hospitals were compared. To evaluate factors registered from noncore hospitals, multivariate analyses were performed for sex, age, living area, type of stroke, and past history of cerebrovascular diseases. Results Annual crude incidence rate for 100,000 residual populations were 428.8 in men and 351.2 in women from core hospitals and 38.5 in men and 43.7 in women from noncore hospitals. Ratios of noncore hospitals against all the hospitals were 8.3% for men and 11.1% for women. Multivariate analyses for age, ischemic type of stroke, past history of cerebrovascular diseases, and living in areas without a core hospital were significant; however, sex was not a significant factor. Conclusion The inventory survey of the stroke registry program in the Iwate prefecture was useful to prevent missing data of stroke cases from noncore hospitals, including patients who are elderly, with ischemic stroke onset, with a past history of stroke, or living in areas without core hospitals.

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.

Equine estrogens (EEs) are widely used in hormone replacement therapy pharmaceuticals for postmenopausal women. Previous studies have shown that EEs occur in the aquatic environment; however, the potential estrogenicity and risk of EEs in aquatic organisms, including fish, have yet to be studied in detail. Therefore, we evaluated the estrogenic potential of major EEs, namely equilin (Eq), 17α-dihydroequilin (17α-Eq), 17β-dihydroequilin (17β-Eq), equilenin (Eqn), 17α-dihydroequilenin (17α-Eqn), and 17β-dihydroequilenin (17β-Eqn), on medaka (Oryzias latipes) using in vivo and in silico assays. Quantitative real-time RT-PCR analyses revealed that expression levels of choriogenin L (ChgL) and choriogenin H (ChgH) in medaka embryos responded to various types and concentrations of EEs in a concentration-dependent manner, whereas transcription levels of vitellogenin 1 were not significantly affected by any of the EEs in the concentration range tested. The order of the in vivo estrogenic potencies of EEs was as follows: 17β-Eq > Eq > 17β-Eqn > Eqn > 17α-Eqn > 17α-Eq. Additionally, the 50% effective concentrations (EC50) of 17β-Eq was lower than that of 17β-estradiol. We also investigated the interaction potential of EEs with medaka estrogen receptor (ER) subtypes in silico using a three-dimensional model of the ligand-binding domain (LBD) for each ER and docking simulations. All six EEs were found to interact with the LBDs of ERα, ERβ1, and ERβ2. The order of the in silico interaction potentials of EEs with each ER LBD was as follows: 17β-Eq > 17α-Eq > Eq > 17β-Eqn > 17α-Eqn > Eqn. Furthermore, we identified the key amino acids that interact with EEs in each ER LBD; our findings suggest that amino acids and/or their hydrogen bonding may be responsible for the ligand-specific interactions with each ER. This study is the first to comprehensively analyze the estrogenic potential of EEs in medaka both in vivo and in silico.

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

In the present study, we investigated transcriptional profiles of estrogen-responsive genes, such as vitellogenins (Vtg1 and Vtg2), choriogenins (ChgL and ChgH) and estrogen receptor subtypes (ERα, ERβ1, and ERβ2), in the liver of male medaka fish (Oryzias latipes) that were exposed to six equine estrogens (1-300 ng l(-1) ) for 3 days. Our quantitative reverse transcription-polymerase chain reaction (RT-PCR) analyses revealed that the expression levels of hepatic Vtg, Chg and ERα genes in male medaka responded to various types and concentrations of equine estrogens. The estrogenic potentials of the tested chemicals were in the order of equilin > 17β-estradiol > equilenin > 17β-dihydroequilin > 17β-dihydroequilenin > 17α-dihydroequilin > 17α-dihydroequilenin, showing the higher estrogenic potential of equilin than that of 17β-estradiol. Our results also showed that the estrogenicities of 17β-dihydroequilin and 17β-dihydroequilenin were more potent than that of 17α-dihydroequilin and 17α-dihydroequilenin. Furthermore, in gene expression analyses of hepatic ER subtypes, observations were made to note that 17β-estradiol and equilin induced ERα transcription in male medaka, and the ERα transcription level had significantly positive correlations with the expression of Vtg and Chg genes. In contrast, in the same 17β-estradiol and equilin treatment groups, it was shown that the transcription levels of hepatic ERβ1 and/or ERβ2 had significantly negative correlations with the expression of Vtg and Chg genes. These results suggested some potential involvement of the ER subtypes in the regulation of Vtg and Chg gene expressions in the liver. This is the first report describing the comprehensive analyses of in vivo estrogenicity of the equine estrogens in male medaka. Copyright © 2016 John Wiley & Sons, Ltd.

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 relative and absolute risks of outcomes other than all-cause death (ACD) attributable to atrial fibrillation (AF) stratified age have not been sufficiently investigated. Methods A prospective study of 23,634 community dwellers aged 40years or older without organic cardiovascular disease (AF=335, non-AF=23,299) was conducted. Multivariate-adjusted rates, rate ratios (RRs) and excess deaths (EDs) for ACD, cardiovascular death (CVD) and non-cardiovascular death (non-CVD), and sex- and age-adjusted RR and ED in middle-aged (40 to 69) and elderly (70years or older) for ACD, CVD, non-CVD, sudden cardiac death (SCD), stroke-related death (Str-D), neoplasm-related death (NPD), and infection-related death (IFD) attributable to AF were estimated using Poisson regression. Results Multivariate-adjusted analysis revealed that AF significantly increased the risk of ACD (RR [95% confidence interval]:1.70 [1.23–2.95]) and CVD (3.86 [2.38–6.27]), but not non-CVD. Age-stratified analysis revealed that AF increased the risk of Str-D in middle-aged (14.5 [4.77–44.3]) and elderly individuals (4.92 [1.91–12.7]), SCD in elderly individuals (3.21 [1.37–7.51]), and might increase the risk of IFD in elderly individuals (2.02 [0.80–4.65], p =0.098). The RR of CVD was higher in middle-aged versus elderly individuals (RRs, 6.19 vs. 3.57) but the absolute risk difference was larger in elderly individuals (EDs: 7.6 vs. 3.0 per 1000person-years). Conclusions Larger absolute risk differences for ACD and CVD attributable to AF among elderly people indicate that the absolute burden of AF is higher in elderly versus middle-aged people despite the relatively small RR.

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

Although several previous studies have demonstrated the presence of equine estrogens in the aquatic environment, limited data are currently available on the endocrine-disrupting potentials in fish and the risks they pose to aquatic organisms. To investigate the interactions of major equine estrogens equilin (Eq) and equilenin (Eqn), as well as their metabolites 17α-dihydroequilin, 17β-dihydroequilin, 17α-dihydroequilenin and 17β-dihydroequilenin, with the estrogen receptor α (ERα) of medaka (Oryzias latipes), a three-dimensional model of the ligand-binding domain (LBD) of ERα was built in silico, and docking simulations were performed. The docking simulation analysis indicated that the interaction of 17β-dihydroequilenin with the ERα LBD is the most potent, followed by those of 17α-dihydroequilin and 17β-dihydroequilin, whereas those of Eq and Eqn were least potent. We further analyzed gene expression profiles in the livers of male medaka exposed to Eq and Eqn. A DNA microarray representing 6000 genes revealed that 24-h exposure to Eq and Eqn (100 ng/L) upregulated the expression of 6 and 34 genes in the livers of males, respectively. Genes upregulated by Eq included the estrogenic biomarker genes vitellogenins and choriogenins, suggesting the estrogenic potential of Eq. In contrast, Eqn exposure upregulated several cancer-related genes, such as mediator complex subunit 16 and RAS oncogene family members, suggesting a carcinogenic potential for Eqn. These results suggest that equine estrogens may have not only endocrine-disrupting potentials via the ERα signaling pathway but also carcinogenic potency in male medaka. Copyright © 2015 John Wiley & Sons, Ltd.

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.

There have been no investigations concerning the association of each blood pressure (BP) reading with future cardiovascular disease (CVD) when multiple measurements are taken on one occasion. This community-based, prospective cohort study (n = 23 344, mean age = 62.4 years) investigated the associations between the BP obtained from the first and second of two consecutive measurements on one occasion and future cardiovascular events in men and women.During the mean follow-up of 5.5 years, 624 CVD events were identified. On the Cox regression analysis of age- and BP-adjusted models, the increased CVD risk of a hypertensive first measurement (systolic BP ≥ 140 mmHg) was independent from the second measurement in men. Even in subjects without a hypertensive second measurement, the CVD risk of the hypertensive first measurement was increased in men. In women, despite a hypertensive first measurement, subjects with a systolic BP 130 mmHg on the second measurement showed a significantly reduced risk for CVD compared with subjects who retained a hypertensive level during the two measurements.An elevated BP on the first measurement should not be disregarded for CVD risk estimation in men, even if the second BP moves to the normal range. In women, elevated BP on the first measurement may have relatively less meaning for CVD prediction if the second BP shifts to a normal range.

Background: Several studies have reported on increases in the incidence of cardiovascular and cerebrovascular diseases after huge earthquakes. An increase in the incidence of cerebrovascular diseases was observed after the Great East Japan Earthquake and Tsunami of 2011. To assess whether tsunami damage or the earthquake was responsible for this trend, we assessed the relative impact of earthquake magnitude and flood damage on cerebrovascular disease. Methods: A total of 12 coastal municipalities facing the epicenter were divided into 4 flood severity groups according to the percentage of people living in the flooded areas (Results: SIRs increased with the increased flood severity: 0.94 (0.59-1.30) at Conclusions: Cerebrovascular disease incidences after the Great East Japan Earthquake and Tsunami of 2011 increased because of tsunami damage and not because of the earthquake magnitude.