Study Profile of the Tsuruoka Metabolomics Cohort Study (TMCS).

The Tsuruoka Metabolomics Cohort Study (TMCS) is an ongoing population-based cohort study being conducted in the rural area of Yamagata Prefecture, Japan. This study aimed to enhance the precision prevention of multi-factorial, complex diseases, including non-communicable and aging-associated diseases, by improving risk stratification and prediction measures. At baseline, 11,002 participants aged 35-74 years were recruited in Tsuruoka City, Yamagata Prefecture, Japan, between 2012 and 2015, with an ongoing follow-up survey. Participants underwent various measurements, examinations, tests, and questionnaires on their health, lifestyle, and social factors. This study used an integrative approach with deep molecular profiling to identify potential biomarkers linked to phenotypes that underpin disease pathophysiology and provide better mechanistic insights into social health determinants. The TMCS incorporates multi-omics data, including genetic and metabolomic analyses of 10,933 participants and comprehensive data collection ranging from physical, psychological, behavioral, and social to biological data. The metabolome is used as a phenotypic probe because it is sensitive to changes in physiological and external conditions. The TMCS focuses on collecting outcomes for cardiovascular disease, cancer incidence and mortality, disability, functional decline due to aging and disease sequelae, and the variation in health status within the body represented by omics analysis that lies between exposure and disease. It contains several sub-studies on aging, heated tobacco products, and women's health. This study is notable for its robust design, high participation rate (89%), and long-term repeated surveys. Moreover, it contributes to precision prevention in Japan and East Asia as a well-established multi-omics platform.

Quantitative prediction of the growth inhibition of various harmful chemicals by statistical analysis of delayed fluorescence decay curves obtained from the green alga Raphidocelis subcapitata.

The toxicity of chemical substances to algal growth is generally measured by the 72-96 h algal growth inhibition test. We have developed a method to assess the toxicity of chemicals in aquatic environments more quickly and simply than conventional testing methods by delayed fluorescence (DF), which reflects the photosynthetic capacity of algae. The DF method is based on a technique for evaluating the amount of change in the decay curve due to the effects of chemicals ([Formula: see text], DF inhibition). Various studies on DF have been reported; however, few reports have evaluated the decay curve of DF by approach using inductive modeling based on measurement data such as principal component analysis (PCA) and partial least squares regression analysis (PLS). Therefore, the purpose of this study is to examine methods for estimating the magnitude and type of toxicity of chemicals by means of a principal component model (PC model) and multiple regression model (MR model) derived from changes in the decay curves of DF of algae exposed to a wide range of 37 toxic substances that have an effect of clear magnitude on algal growth. The changes in the DF decay curves due to exposure the 37 toxic substances to algae were summarized in the PC model composed of eigenvectors and scores of four principal components. For validation of usefulness, a hierarchical cluster analysis (HCA) of the amount of change in four PC scores revealed that the growth inhibition rate was more influential than the chemical type. We also found the possibility of quantitatively predicting the growth inhibition of chemicals by MR model by the amount of change in the PC scores.

Changes in Smoking Habits and Behaviors Following the Introduction and Spread of Heated Tobacco Products in Japan and Its Effect on FEV1 Decline: A Longitudinal Cohort Study.

BACKGROUND: Heated tobacco product (HTP) use in Japan has rapidly increased. Despite this rapid spread, little is known about the health effects of HTP use. We conducted a longitudinal cohort study to investigate the change in smoking habits following the spread of HTP use and its effect on forced expiratory volume in 1 second (FEV1) decline. METHODS: Participants consisted of a resident population (n = 2,612; mean age, 67.7 years) with FEV1 measurement in 2012-2014 and 2018-2019, and a worksite population (n = 722; mean age 49.3 years) without FEV1 data. Participants were categorized as combustible cigarette-only smokers, HTP-only users, dual users, past smokers, and never smokers. The association between smoking group and the change in smoking consumption over a mean 5.6 years was examined. Differences in annual FEV1 change between smoking groups were examined in the resident population. RESULTS: Prevalence of HTP-only and dual users in 2018-2019 was 0.8% and 0.6% in the resident population, and 5.0% and 1.9% in the worksite population, respectively. The overall number of tobacco products smoked/used increased in dual users compared to baseline, but not in others. Annual FEV1 decline in dual users tended to be greater than that in cigarette-only smokers (16; 95% confidence interval, -34 to 2 mL/year after full adjustment). Participants switching to HTP-only use 1.7 years before had a similar FEV1 decline as cigarette-only smokers. CONCLUSIONS: HTP use, including dual use, is prevalent even in a rural region of Japan. Dual users appear to smoke/use tobacco products more and have a greater FEV1 decline. Tobacco policy should consider dual use as high-risk.

Validity Assessment of Self-reported Medication Use for Hypertension, Diabetes, and Dyslipidemia in a Pharmacoepidemiologic Study by Comparison With Health Insurance Claims.

BACKGROUND: Although self-reported questionnaires are widely employed in epidemiologic studies, their validity has not been sufficiently assessed. The aim of this study was to evaluate the validity of a self-reported questionnaire on medication use by comparison with health insurance claims and to identify individual determinants of discordance in the Tsuruoka Metabolomics Cohort Study. METHODS: Participants were 2,472 community-dwellers aged 37 to 78 years from the Tsuruoka Metabolomics Cohort Study. Information on lifestyle and medications was collected through a questionnaire. Sensitivity and specificity were determined using health insurance claims from November 2014 to March 2016, which were used as a standard. Potential determinants of discordance were assessed using multivariable logistic regression. RESULTS: The self-reported questionnaire on medication use showed high validity. Sensitivity and specificity were 0.95 (95% CI, 0.93-0.96) and 0.97 (95% CI, 0.96-0.98) for antihypertensive medications, 0.94 (95% CI, 0.91-0.97) and 0.98 (95% CI, 0.98-0.99) for diabetes medications, and 0.84 (95% CI, 0.82-0.87) and 0.98 (95% CI, 0.97-0.99) for dyslipidemia medications, respectively. Males without high education and those who currently smoke cigarettes were found to be associated with discordant reporting which affected sensitivity, especially those with medication use for dyslipidemia. CONCLUSIONS: In this population-based cohort study, we found that the self-reported questionnaire on medication use was a valid measure to capture regular medication users. Sensitivity for dyslipidemia medications was lower than those for the other medications. Type of medication, sex, education years, and smoking status influenced discordance, which affected sensitivity in self-reporting.

Risk of bladder cancer in male Japanese workers exposed to ortho-toluidine and other aromatic amines.

PURPOSE: Nine bladder cancer (BCa) cases were reported among aromatic amine-exposed male workers at a factory manufacturing organic dye/pigment intermediates in Japan. We aimed to evaluate the characteristics of aromatic amine-exposed workers by cross-sectional observation, and the risk of BCa by assessing the standardized incidence ratio (SIR). METHODS: In the cross-sectional study, our subjects were: 9 BCa patients, 36 aromatic amine-exposed non-patients, and 79 non-exposed workers from 3 factories. We evaluated the subjects' medical history, urinalysis, qualitative determination of nuclear matrix protein 22, and urinary cytology. For SIR assessment, 98 aromatic amine-exposed workers from 1 factory were included, and the Japanese general male population was used as a referent population. Since no direct aromatic amine-exposure data were available, we calculated surrogate exposure levels using information on job sites, exposure potency, and duration. RESULTS: Coexistent aromatic amines were ortho-toluidine (OT), aniline, para-toluidine, ortho-anisidine, 2,4-xylidine, and ortho-chloroaniline. The prevalence rates of cystitis and bladder lesion-related symptoms in both BCa patients and aromatic amine-exposed non-patient workers were significantly higher than those of non-exposed workers. Overall, the SIR for BCa in OT-exposed workers was 56.8 (95% CI 27.7-104.3) and apparent dose-response relationships were revealed between the SIR and the surrogate exposure level in the 0-10-year lagged analyses. Overall, SIRs in other aromatic amine-exposed workers were also significantly high but no or unclear dose-response relationships were observed. CONCLUSIONS: We conclude that OT may be responsible for the increased risk of BCa. Regular monitoring of bladder lesion-related symptoms is essential for the early identification of BCa.

Association of blood cadmium levels in pregnant women with infant birth size and small for gestational age infants: The Japan Environment and Children's study.

BACKGROUND: There is growing evidence of an association between cadmium (Cd) and unfavorable birth outcomes. The effect of Cd exposure on anthropometric measures at birth or small for gestational age (SGA) infants in a large, nationwide Japanese cohort remains to be clarified. OBJECTIVES: To analyze the association between maternal blood Cd levels at different sampling times and sex-dependent infant birth size, weight, body length, chest, and head circumferences, in addition to SGA. METHODS: Data of 17,584 pregnant women in the Japan Environment and Children's Study were analyzed for anthropometric measurements. For SGA determination, 13,969 cases of vaginal delivery were analyzed after excluding infants born by cesarean section. Maternal blood Cd levels were categorized into quartiles (Q1-Q4), and the Q1 was used as a reference. Multiple linear regression analysis was performed for anthropometric measurements, and multiple logistic regression analysis was used to investigate the association of maternal blood Cd levels with the risk of SGA. RESULTS: Birth weight tended to decrease according to the increase in quartiles of blood Cd levels (15.63 g decrease [95% confidence level (CI): -33.26, 2.01] for Q4). The overall analysis revealed no decreases in body length and head and chest circumference, but subgroup analysis revealed that chest circumference tended to decrease according to the increase in quartiles in the female sex/third-trimester stratification (0.16 cm decrease [95% CI: -0.32, 0.00] for Q4). SGA risk was also higher and paralleled the increase in blood Cd levels associated with the female sex/third-trimester group (Odds Ratio 1.90 [95% CI: 1.23, 2.94] for Q4). CONCLUSION: Our results provide further evidence of sex-specific health risks associated with Cd exposure in early life in a large Japanese pregnancy cohort.

Association between Asian dust exposure and respiratory function in children with bronchial asthma in Nagasaki Prefecture, Japan.

BACKGROUND: Studies on the adverse effects of Asian dust (AD) on respiratory function in children are scarce. The objective of this study was to examine the association between AD and respiratory function by measuring peak expiratory flow rates (PEFRs) in asthmatic children. METHODS: The study was carried out from March to May from 2014 through 2016. One hundred ten children with bronchial asthma were recruited from four hospitals in the Goto Islands and south Nagasaki area in Nagasaki prefecture. The parents were asked to record their children's PEFRs every morning/evening and clinical symptoms in an asthma diary. AD was assessed from light detection and ranging data, and a linear mixed-effects model was used to estimate the effects of AD on daily PEFR. Time-stratified case-crossover analyses were performed to examine the association between AD and asthma attacks defined by reduction levels in PEFR. RESULTS: AD was detected on 11 days in the Goto Islands, and on 23 days in the south Nagasaki area. After adjusting for age, sex, temperature, and daily oxidants, we found a consistent association between AD and a 1.1% to 1.7% decrease in PEFR in the mornings and a 0.7% to 1.3% decrease in the evenings at a lag of 0 to 5 days. AD was not associated with the number of asthma attacks, respiratory symptoms, or other symptoms at any lag days examined. CONCLUSIONS: Exposure to AD was associated with reduced PEFR, although the effects were not large enough to induce clinically apparent symptoms, in clinically well-controlled asthmatic children.

Predictive factors for liver volume and function recovery after resection using three-dimensional analysis.

BACKGROUND: Clinical and biological factors that predict liver volume recovery rate (LVRR) after liver resection of different resected volume (RV) have not been studied extensively. Moreover, it remains uncertain whether remnant liver volume influences the liver function recovery rate (LFRR). This study examined the predictive factors for LVRR after liver resections of different RV and investigated LFRR by focusing on LVRR improvements after hepatectomy. METHODS: Patients who underwent hepatectomy between January 2013 and August 2015 were reviewed retrospectively. LVRR and LFRR were assessed at postoperative months (POMs) 3, 6, and 12. LVRR was evaluated on the basis of RV (0%-15%, 15%-30%, 30%-45%, and >45%). LFRR was evaluated using total bilirubin, prothrombin time, and platelet count. RESULTS: LVRR was lower with more extensive liver resections. Significant independent predictors of LVRR were type IV collagen 7s domain levels and resection magnitude. Platelet count correlated positively with LVRR at all POMs. CONCLUSIONS: Resected livers regenerated after surgery but did not reach preoperative volumes. Preserving the liver as much as possible during resection can result in greater LFRR after hepatectomy. Therefore, decisions regarding liver resection volume should be made very carefully, particularly in patients with higher type IV collagen 7s domain levels.

Efficient hydrogen production using photosystem I enhanced by artificial light harvesting dye.

In this study, we improved the hydrogen production efficiency by combining photosystem I with an artificial light harvesting dye, Lumogen Red. In the reaction system, Lumogen Red allows light absorption and energy transfer to photosystem I by Förster resonance energy transfer; therefore, the Pt nanoparticles act as active sites for hydrogen generation.

Association between blood manganese level during pregnancy and birth size: The Japan environment and children's study (JECS).

BACKGROUND: Manganese (Mn) is both an essential element and a potential toxicant. Although a few studies have suggested a nonlinear relationship between the maternal whole blood Mn level at delivery and infant birth weight, little is known about the effects of Mn levels during pregnancy on fetal growth, particularly with regard to sex-specific differences. METHODS: In this nationwide birth cohort study, we examined the association of maternal blood Mn level during pregnancy with infant birth weight, length, and head circumference in 16,473 mother-infant pairs. Pregnant women living in 15 regions across Japan were recruited between January 2011 and March 2014. The analysis of birth size (8,484 males and 7,989 females) was conducted using a nonlinear spline, followed by the use of quadratic regression or linear regression models. The analysis of small-for-gestational-age (SGA) (6,962 males and 6,528 females born vaginally) was conducted using multivariate logistic regression. Additionally, subgroup analysis was conducted according to the timing of blood sampling. RESULTS: The median maternal blood Mn level during pregnancy (i.e., 2nd and 3rd trimesters) was 16.2 µg/L (range, 4.3-44.5 µg/L). A positive linear association between the log blood Mn level and head circumference was observed in both male and female infants. However, a nonlinear relationship between the log blood Mn level and birth weight was observed only in male infants, such that the birth weight increased up to a blood Mn level of 18.6 µg/L. In the subgroup analysis stratified by the timing of maternal blood sampling, this nonlinear relationship was obvious only when sampling was performed in the 3rd trimester. Male infants in the lowest blood Mn level quartile (≤ 13.2 µg/L) faced an increased risk of SGA (odds ratio [95% confidence interval] = 1.35 [1.04-1.74]), as did those in the highest blood Mn level quartile (≥ 21.0 µg/L) when sampling was performed during the 3rd trimester (odds ratio [95% confidence interval] = 1.62 [1.10 to 2.39]), compared to those in the third blood Mn level quartile (the category including 18.6 µg/L). No association of blood Mn level with birth weight was observed among female infants, and blood Mn level was not associated with birth length in either male or female infants. CONCLUSION: A low blood Mn level during pregnancy or a high blood Mn level during the 3rd trimester was associated with a lower birth weight and increased risk of SGA in male infants, but not in female infants. A low blood Mn level was found to correlate slightly with a small head circumference among infants of both sexes.

KRAS mutations in cell-free DNA from preoperative and postoperative sera as a pancreatic cancer marker: a retrospective study.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has very poor prognosis despite existing multimodal therapies. This study aimed to investigate whether KRAS mutations at codons 12/13 in cell-free DNA (cfDNA) from preoperative and postoperative sera from patients with PDAC can serve as a predictive biomarker for treatment response and outcomes after surgery. METHODS: Preoperative and postoperative serum samples obtained from 45 patients with PDAC whom underwent curative pancreatectomy at our institution between January 2013 and July 2016 were retrospectively analysed. Peptide nucleic acid-directed PCR clamping was used to identify KRAS mutations in cfDNA. RESULTS: Among the 45 patients enrolled, 11 (24.4%) and 20 (44.4%) had KRAS mutations in cfDNA from preoperative and postoperative sera, respectively. Multivariate analysis revealed that KRAS mutations in postoperative serum (hazard ratio (HR)=2.919; 95% confidence interval (CI)=1.109-5.621; P=0.027) are an independent prognostic factor for disease-free survival. Furthermore, the shift from wild-type KRAS in preoperative to mutant KRAS in postoperative cfDNA (HR=9.419; 95% Cl=2.015-44.036; P=0.004) was an independent prognostic factor for overall survival. CONCLUSIONS: Changes in KRAS mutation status between preoperative and postoperative cfDNA may be a useful predictive biomarker for survival and treatment response.

Post-progression survival following second-line chemotherapy in patients with advanced pancreatic cancer previously treated with gemcitabine: a meta-analysis.

Background Post-progression survival (PPS) could be a confounding element in interpreting data from clinical trials of second-line chemotherapy in patients with advanced pancreatic cancer (PC) previously treated with gemcitabine (GEM) because a recent meta-analysis of oxaliplatin combination therapy showed statistical heterogeneity for overall survival (OS) but not for progression-free survival (PFS). This study aimed to improve the understanding of the impact of PPS on OS in this setting. Methods Databases were searched to identify randomized controlled trials (RCTs) in the salvage setting. We evaluated relationships between OS and PFS, PPS, and other variables. Results Totally, 17 RCTs with 3253 patients were identified. Median OS was strongly and moderately associated with median PPS and PFS, respectively (r = 0.913; p < 0.001 and 0.780; p < 0.001, respectively). The proportion of patients with good performance status was significantly associated with both PPS and PFS (r = 0.574, p < 0.001 and 0.492, p < 0.001, respectively). The induction rate of subsequent chemotherapy was related to the duration of PPS and OS (r = 0.640, p < 0.001 and 0.647, p < 0.001, respectively). Median PPS and OS were significantly longer in recent trials than those in older trials (3.55 versus 2.78 months, p < 0.001 and 6.29 versus 5.02 months, p < 0.001). Conclusions Median PPS was strongly correlated with median OS. Given the recently increased opportunity for subsequent chemotherapy and supportive care, PPS may serve as an important element to clarify problems in this setting.

Community-wide physical activity intervention based on the Japanese physical activity guidelines for adults: A non-randomized controlled trial.

Very few community intervention studies that promote physical activity (PA) using guidelines and its dissemination and implementation have been conducted. Consequently, we evaluated the effectiveness of a community-wide intervention (CWI) of PA with adults based on the Japanese guidelines for promoting PA. This was a non-randomized controlled trial, with four administrative districts in Fujisawa city assigned to the intervention group and nine to the control group. The CWI, conducted from 2013 to 2015, comprised information dissemination, education, and community support. The primary outcome was change in PA participation. Secondary outcomes were CWI awareness and PA guideline knowledge. Outcomes were assessed using questionnaires distributed to two independent, random samples of 3000 community-based adults (aged ≥20years). Two separate samples-1230 adults at baseline and 1393 at the two-year follow-up-responded to the survey. The median time spent in PA did not differ between intervention and control groups after adjusting for potential confounders (adjusted difference between groups=-0.02min/day [95% confidence interval (CI): -0.11, 0.10]). However, intervention group participants were more aware of the CWI (33.8%) than were control group participants (25.2%) at the two-year follow-up (odds ratio=1.44 [95% CI: 1.06, 1.95]). A significant difference was also observed in participants' PA guideline knowledge (adjusted difference between groups=0.82% [95% CI: 0.33, 1.31]). Although significant differences in awareness and knowledge were observed between groups, this CWI did not change PA levels over two years. Future studies should investigate the long-term effects of CWIs beyond two years. TRIAL REGISTRATION NUMBER: UMIN-CTR UMIN000018389.

Questionnaire results on exposure characteristics of pregnant women participating in the Japan Environment and Children Study (JECS).

BACKGROUND: The Japan Environment and Children's Study (JECS) is a nation-wide birth cohort study investigating environmental effects on children's health and development. In this study, the exposure characteristics of the JECS participating mothers were summarized using two questionnaires administered during pregnancy. METHODS: Women were recruited during the early period of their pregnancy. We intended to administer the questionnaire during the first trimester (MT1) and the second/third trimester (MT2). The total number of registered pregnancies was 103,099. RESULTS: The response rates of the MT1 and MT2 questionnaires were 96.8% and 95.1%, respectively. The mean gestational ages (SDs) at the time of the MT1 and MT2 questionnaire responses were 16.4 (8.0) and 27.9 (6.5) weeks, respectively. The frequency of participants who reported "lifting something weighing more than 20 kg" during pregnancy was 5.3% for MT1 and 3.9% for MT2. The Cohen kappa scores ranged from 0.07 to 0.54 (median 0.31) about the occupational chemical use between MT1 and MT2 questionnaires. Most of the participants (80%) lived in either wooden detached houses or steel-frame collective housing. More than half of the questionnaire respondents answered that they had "mold growing somewhere in the house". Insect repellents and insecticides were used widely in households: about 60% used "moth repellent for clothes in the closet," whereas 32% applied "spray insecticide indoors" or "mosquito coil or an electric mosquito repellent mat." CONCLUSIONS: We summarized the exposure characteristics of the JECS participants using two maternal questionnaires during pregnancy.

Cardiovascular events and death in Japanese patients with chronic kidney disease.

The incidence of cardiovascular disease (CVD) is higher in patients with chronic kidney disease (CKD) than in the general population, and the risk of CVD increases with reductions in renal function. However, the incidence of CVD in Japanese patients with CKD has not been sufficiently investigated. To measure this we conducted the Chronic Kidney Disease Japan Cohort (CKD-JAC) Study over four years in 2,966 Japanese patients with CKD to examine the incidence of CVD and all-cause death. These patients had an estimated glomerular filtration rate (eGFR) of 10-59 ml/min/1.73 m2, were under nephrologist care, and pooled from 17 medical institutions in Japan. At the median follow-up of 3.9 years, 69 patients had died, 217 had cardiovascular events, and 514 started maintenance dialysis therapy. The incidences of cardiovascular events were 11.9, 19.1, 25.0, and 39.4 per 1,000 person-years at eGFRs of 45-59, 30-44, 15-29, and under 15 ml/min/1.73 m2, respectively. The adjusted Cox proportional hazards models showed that the risk of cardiovascular events increased as the eGFR decreased, with a significant difference only between CKD stage G5 (eGFR: under 15 ml/min/1.73 m2) and CKD stage G3a (eGFR: 45-59 ml/min/1.73 m2) (hazard ratio 3.16, 95% confidence interval 1.28 to 7.76). Thus, the risk of CVD and all-cause death was related to the decrease in eGFR, but not necessarily elevated in proportion to progression of the CKD stage in Japanese patients with predialysis CKD under a nephrologist's care.

Risk factors for CKD progression in Japanese patients: findings from the Chronic Kidney Disease Japan Cohort (CKD-JAC) study.

BACKGROUND: Chronic kidney disease (CKD) eventually progresses to end-stage renal disease (ESRD). However, risk factors associated with CKD progression have not been well characterized in Japanese patients with CKD who are less affected with coronary disease than Westerners. METHODS: A large-scale, multicenter, prospective, cohort study was conducted in patients with CKD and under nephrology care, who met the eligibility criteria [Japanese; age 20-75 years; and estimated glomerular filtration rate (eGFR): 10-59 mL/min/1.73 m2]. The primary endpoint was a composite of time to a 50 % decline in eGFR from baseline or time to the initiation of renal replacement therapy (RRT). The secondary endpoints were the rate of decline in eGFR from baseline, time to a 50 % decline in eGFR from baseline, time to the initiation of RRT, and time to doubling of serum creatinine (Cre) concentration. RESULTS: 2966 patients (female, 38.9 %; age, 60. 3 ± 11.6 years) were enrolled. The incidence of the primary endpoint increased significantly (P < 0.0001) in concert with CKD stage at baseline. The multivariate Cox proportional hazards models revealed that elevated systolic blood pressure (SBP) [hazard ratio (HR) 1.203, 95 % confidence interval (CI) 1.099-1.318)] and increased albumin-to-creatinine ratio (UACR ≥ 1000 mg/g Cre; HR: 4.523; 95 % CI 3.098-6.604) at baseline were significantly associated (P < 0.0001, respectively) with the primary endpoint. CONCLUSIONS: Elevated SBP and increased UACR were risk factors that were significantly associated with CKD progression to ESRD in Japanese patients under nephrology care. UMIN clinical trial registry number: UMIN000020038.

The effects of community-wide dissemination of information on perceptions of palliative care, knowledge about opioids, and sense of security among cancer patients, their families, and the general public.

PURPOSE: Prejudices against palliative care are a potential barrier to quality end-of-life care. There have been few large-scale community-wide interventions to distribute appropriate information about palliative care, and no studies have investigated their impact on cancer patients, their families, and the general public. Thus, we conducted a 3-year community intervention and evaluated the effects of distributing such information at the community level, and explored associations among levels of exposure, perceptions, knowledge, and the sense of security achieved. METHODS: Over a period of 3 years, we provided flyers, booklets, posters, and public lectures about palliative care in four regions of Japan, and carried out pre- and post-intervention surveys with repeated cross-sectional samplings of cancer patients (pre 859, post 857), bereaved family members (1110, 1137), and the general public (3984, 1435). The levels of exposure to the provided information were measured by a multiple-choice questionnaire after intervention. Multiple logistic regression analyses were used to estimate multivariable-adjusted odds ratios (ORs) for perceptions of palliative care, knowledge about opioids, and sense of security among the exposure groups. RESULTS: Overall perceptions of palliative care, opioids, and receiving care at home improved significantly among the general public and families, but not among the patients at the community level. However, multiple regression revealed that patients of extensive exposure category had significantly more positive perceptions of palliative care to those of non-exposure category (p = 0.02). The sense of security regarding cancer care of all patients, family members, and the general public improved. Among others, the respondents who reported extensive exposure in the general public and family members scored significantly higher sense of security. CONCLUSION: Our findings indicate that providing palliative care information via small media and lectures in the community is effective in improving perceptions of palliative care and knowledge about opioids among the community dwellers, especially for caregivers of the patients. The acquisition of adequate knowledge about palliative care from various information sources may improve people's sense of security regarding cancer.

Asian Dust and Pediatric Emergency Department Visits Due to Bronchial Asthma and Respiratory Diseases in Nagasaki, Japan.

BACKGROUND: The adverse health effects of Asian dust (AD) on the respiratory system of children are unclear. We hypothesized that AD events may lead to increased visits by children to emergency medical centers due to bronchial asthma and respiratory diseases, including bronchial asthma. METHODS: We used anonymized data on children receiving primary emergency treatment at Nagasaki Municipal Primary Emergency Medical Center, Japan between March 2010 and September 2013. We used Light Detection and Ranging (LIDAR) data to assess AD exposure and performed time-stratified case-crossover analyses to examine the association between AD exposure and emergency department visits. The main analysis was done with data collected from March through May each year. RESULTS: The total number of emergency department visits during the study period was 756 for bronchial asthma and 5421 for respiratory diseases, and the number of "AD days" was 47. In school children, AD events at lag day 3 and lag day 4 were associated with increased emergency department visits due to bronchial asthma, with odds ratios of 1.837 (95% confidence interval [CI], 1.212-2.786) and 1.829 (95% CI, 1.179-2.806), respectively. AD events were significantly associated with respiratory diseases among preschool children at lag day 0, lag day 1, and lag day 2, with odds ratios of 1.244 (95% CI, 1.128-1.373), 1.314 (95% CI, 1.189-1.452), and 1.273 (95% CI, 1.152-1.408), respectively. These associations were also significant when the results were adjusted for meteorological variables and other air pollutants. CONCLUSIONS: The study findings suggested that AD exposure increases emergency department visits by children.

Metabolomic profiling reveals novel biomarkers of alcohol intake and alcohol-induced liver injury in community-dwelling men.

OBJECTIVE: Metabolomics is a promising approach to the identification of biomarkers in plasma. Here, we performed a population-based, cross-sectional study to identify potential biomarkers of alcohol intake and alcohol-induced liver injury by metabolomic profiling using capillary electrophoresis-mass spectrometry (CE-MS). METHODS: Fasting plasma samples were collected from 896 Japanese men who participated in the baseline survey of the Tsuruoka Metabolomics Cohort Study, and 115 polar metabolites were identified and absolutely quantified by CE-MS. Information on daily ethanol intake was collected through a standardized, self-administered questionnaire. The associations between ethanol intake and plasma concentration of metabolites were examined. Relationships between metabolite concentrations or their ratios and serum liver enzyme levels in the highest ethanol intake group (>46.0 g/day) were then examined by linear regression analysis. Replication analysis was conducted in 193 samples collected from independent population of this cohort. RESULTS: Nineteen metabolites were identified to have an association with daily alcohol consumption both in the original and replication population. Three of these metabolites (threonine, glutamine, and guanidinosuccinate) were found to associate well with elevated levels of serum liver enzymes in the highest ethanol intake group, but not in the non-drinker group. We also found that the glutamate/glutamine ratio had a much stronger relation to serum γ-glutamyltransferase, aspartate transaminase, and alanine transaminase than glutamate or glutamine alone (standardized beta = 0.678, 0.558, 0.498, respectively). CONCLUSIONS: We found 19 metabolites associated with alcohol intake, and three biomarker candidates (threonine, guanidinosuccinate and glutamine) of alcohol-induced liver injury. Glutamate/glutamine ratio might also be good biomarker.