Heavy metals and trace elements in maternal blood and prevalence of congenital limb abnormalities among newborns: the Japan Environment and Children's Study.

BACKGROUND: Heavy metals such as lead (Pb) and cadmium (Cd) have been associated with adverse pregnancy and developmental outcomes, including congenital abnormalities. This study investigated the association between exposure to heavy metals and trace elements during fetal life and congenital limb abnormalities in infants. METHODS: This study is based on a prospective ongoing nationwide birth cohort from the Japan Environment and Children's Study (JECS). The concentrations of Cd, Pb, mercury (Hg), selenium (Se), and manganese (Mn) were measured in maternal blood collected during the mid-late trimesters. Inclusion criteria were available from questionnaires filled in during pregnancy, including information about congenital limb abnormalities at birth or at one month. To examine the associations with limb anomalies and individual chemicals, logistic regression models were applied following log-transformation or division into quartiles of Cd, Pb, Hg, Se, and Mn concentrations. To assess the associations with the heavy metals and trace elements mixture, quantile g-computation was employed. All models were adjusted for age, maternal smoking history, maternal alcohol intake, history of smoking, and infant sex. RESULTS: Data from 90,163 participants were included in the analysis, of whom 369 had congenital limb abnormalities in any of the collected information, and 89,794 had none. Among the 369 cases of congenital limb abnormalities, there were 185 and 142 cases of polydactyly and syndactyly, respectively. The median concentrations of Pb, Cd, Hg, Se, and Mn were 5.85, 0.66, 3.64, 168, and 15.3 ng/g, respectively. There were no associations between maternal blood concentrations of Pb [adjusted odd ratio = 0.83; 95% confidence interval = 0.61, 1.11], Cd [0.87; 0.68, 1.10], Hg [0.88; 0.73, 1.07], Se [1.07; 0.44, 2.59], and Mn [0.91; 0.64, 1.30] with congenital limb abnormalities. No significant association was observed between the mixture of heavy metals and trace elements [0.85; 0.72, 1.02] and any congenital limb abnormalities. Moreover, there was no association with all polydactylies and all syndactylies, or any type of abnormality as a subdivision. CONCLUSION: At the maternal exposure levels of Cd, Pb, Hg, Se, and Mn assessed in the present study, no association was identified with the risk of developing congenital limb abnormalities in children.

Maternal pre-pregnancy body mass index and related factors: A cross-sectional analysis from the Japan Environment and Children's Study.

Socioeconomic status and smoking are reportedly associated with underweight and obesity; however, their associations among pregnant women are unknown. This study aimed to investigate whether socioeconomic factors, namely educational attainment, household income, marital status, and employment status, were associated with pre-pregnancy body mass index (BMI) categories, including severe-moderate underweight (BMI ≤ 16.9 kg/m2), mild underweight (BMI, 17.0-18.4 kg/m2), overweight (BMI, 25.0-29.9 kg/m2), and obese (BMI ≥ 30.0 kg/m2) among Japanese pregnant women using data from the Japan Environment and Children's Study (JECS). In total, pregnant women were included 96,751. Age- and parity-adjusted multivariable multinomial logistic regression analyses assessed socioeconomic factors and smoking associations with falling within abnormal BMI categories (normal BMI as the reference group). Lower education and lower household were associated with overweight and obesity, and, especially, lowest education and household income had relatively higher point estimate relative ratios (RRs) of 3.97 and 2.84, respectively. Regarding the risks for underweight, however, only junior high school education had a significantly higher RR for severely to moderately underweight. Regarding occupational status, homemakers or the unemployed had a higher RR for severe-moderate underweight, overweight, and obesity. Unmarried, divorced, or bereaved women had significantly higher RRs for mildly underweight status. Quitting smoking early in pregnancy/still smoking had higher RRs for all four not having normal BMI outcomes; however, quitting smoking before pregnancy had a higher RR only for obese individuals. Lower educational attainment and smoking are essential intervention targets for obesity and severe-moderate underweight prevention in younger women. Lower household income is also a necessary target for obesity.

Factors related to the resignation and migration of physicians in public health administration agencies using nationwide survey data in Japan.

BACKGROUND: Physicians in public health administration agencies (public health physicians: PHP) play important roles in public health; however, there are not enough such physicians in Japan. This study aimed to elucidate the factors related to the resignation and migration of PHPs using nationwide survey data. METHODS: Data from the Survey of Physicians, Dentists, and Pharmacists (2010, 2012, 2014, and 2016) were analyzed. The outcome was the resignation of PHPs or migration to public health administration agencies. The explanatory variables in the resignation analysis were age, sex, workplace, and board certification status. The type of work was added as an explanatory variable in the migration analysis, and clinical specialty was added to the clinical doctor-restricted analysis. The odds ratios (ORs) of the explanatory variables were calculated using generalized estimation equations. RESULTS: In the resignation analysis among PHPs, women had a significantly lower OR, whereas younger PHPs and those with board certifications had significantly higher ORs. In the migration to public health administration agencies analysis among medical doctors, women and those aged between 35 and 39 years had significantly higher ORs, but those with board certifications had significantly lower ORs. Hospital/clinic founders or directors had significantly lower ORs, but the clinic staff and 'others/not working' had significantly higher ORs. In the migration to public health administration agencies analysis among clinical physicians, those aged between 35 and 39 years had significantly higher ORs. Still, those with two or more board certifications had significantly lower ORs. Hospital/clinic founders or directors had significantly lower ORs, but the clinic staff had significantly higher ORs. Clinical doctors specializing in surgery and other specialties had significantly lower ORs, but those specializing in pediatrics and psychiatry/psychosomatic medicine had significantly higher ORs. CONCLUSIONS: Having board certifications were significantly related to the resignation of PHPs and migration to public health administration agencies. Women migrated to public health administration agencies more than men and younger PHPs were more likely to resign. However, medical doctors aged between 35 and 39 years were more likely to migrate to public health administration agencies. Similarly, clinic staff, non-clinical physicians, and those whose specialties were pediatrics and psychiatry/psychosomatic medicine were more likely to migrate to public health administration agencies.

Evaluating association of smoking status during pregnancy with adverse birth outcomes using urinary cotinine concentration: The Japan environment and Children's study (JECS).

Urinary cotinine concentration (UCC) reflects smoking status. However, in pregnant women, its association with adverse birth outcomes related to fetal growth is not widely known. Thus, we aimed to explore this relationship by focusing on dose-response relationships. We investigated 86,638 pregnant women enrolled between 2011 and 2014 in a prospective cohort study in Japan and observed three birth outcomes (preterm birth, low birth weight, and small-for-gestational age). We measured UCC in the second or third trimester, and categorized the participants using cut-off values (negative cotinine concentration, passive cotinine concentration, and active cotinine concentration corresponding to non-smokers, passive smokers, and active smokers, respectively). Logistic regression analyses were conducted to evaluate the risks, and dose-response relationships were visualized using restricted cubic spline curves. Analyses based on self-reported smoking status were also performed. We found that in low active and highly active cotinine concentrations, the adjusted odds ratios (aORs) of birth outcomes were significantly increased (preterm birth, 1.24 [95% CI 1.06-1.46], 1.39 [95% CI 1.19-1.62]; low birth weight, 1.40 [95% CI 1.24-1.58], 2.27 [95% CI 2.05-2.53]; small-for-gestational age, 1.35 [95% CI 1.19-1.52], 2.39 [95% CI 2.16-2.65]). Restricted cubic spline curves demonstrated risk elevations in the active cotinine concentration range. Our research revealed dose-response relationships between UCC during pregnancy and the risks of preterm birth, low birth weight, and small-for-gestational age. Measurement of UCC to ascertain smoking status during pregnancy may be a useful approach for predicting the risks of these birth outcomes.

Association between maternal caffeine intake during pregnancy and child development at 6 and 12 months: The Japan Environment and Children's Study.

BACKGROUND: Caffeine intake by pregnant women may have neurodevelopmental effects on the fetus due to adenosine antagonism. However, there are insufficient data and inconsistent results from epidemiological studies on the effect of maternal caffeine intake on child development. AIMS: This study examined the association between mothers' estimated caffeine intake during pregnancy and their children's score on the Japanese version of the Ages & Stages Questionnaires™ (J-ASQ) at 6 and 12 months of age. STUDY DESIGN: The study is a part of nationwide prospective birth-cohort study: the Japan Environment and Children's Study. SUBJECTS: In total, 87,106 participants with the Food Frequency Questionnaire (FFQ) data and J-ASQ at 6 or 12 months of age were included in the study. OUTCOME MEASURES: The data were analyzed by logistic regression analysis to determine whether the scores of the five subscales on the J-ASQ were below the cutoff point as the dependent variable. RESULTS: The results showed that children born to mothers who consumed >300 mg caffeine per day had a 1.11-fold increased odds of gross motor developmental delay at 12 months of age (adjusted odds ratio [AOR] = 1.114 [95 % CI: 1.013-1.226]). CONCLUSIONS: Issues in gross motor development can emerge prior to future developmental issues. Therefore, further studies on developmental outcomes in older children, including the future outcomes of the children who participated in this study, are needed.

Five-minute test to prevent postcardiotomy reexploration.

Objective: To evaluate the effectiveness of the 5-minute test (FMT), developed to record the amount of pericardial bleeding in patients undergoing general cardiac surgery, and determine the relationship between this test and postcardiotomy bleeding. Methods: The medical records of 573 patients who underwent adult cardiac surgery between January 2016 and December 2019 were reviewed retrospectively. Patients were divided into 2 groups: the FMT group included patients who underwent general cardiac surgery between January 2018 and December 2019 (n = 278), and the control group included patients who underwent general cardiac surgery between January 2016 and December 2017 (n = 295). The postcardiotomy reexploration rate due to intrapericardial bleeding or cardiac tamponade within 1 week after surgery and the amount of bleeding until 2 days after surgery were compared. The FMT procedure involved counting the amount of bleeding by packing 4 to 6 surgical gauze sheets for 5 minutes. Sternal closure was performed when the amount of blood measured by the FMT was <100 g. Results: Compared with the control group, the FMT group had a significantly lower incidence of postcardiotomy reexploration (1.5% vs 5.7%; P = .007) and a reduced amount of bleeding after cardiac surgery (median, 1165 mL [interquartile range (IQR), 756.2-1743.8 mL] versus 1440 mL [IQR, 825.0-2130.0 mL]; P = .005). There was a significant positive correlation between the FMT gauze sheet weight and postcardiotomy bleeding (r = 0.322; P < .001). Conclusions: The FMT is an objective and effective tool for estimating postoperative bleeding during cardiac surgery that can prevent postcardiotomy reexploration and reduce the amount of postcardiotomy bleeding.

Recombinant Activated Factor VII in Aortic Surgery for Patients Under Hypothermic Circulatory Arrest.

Purpose: We aimed to identify the risk factors of critical bleeding and investigate the safety of recombinant activated factor VII (rFVIIa) in aortic surgery under hypothermic circulatory arrest (HCA). Patients and Methods: The present single-center retrospective study compared the baseline characteristics of 144 patients who underwent aortic surgery under HCA at our institute. Among the total cohort of 144 patients, 42 received rFVIIa (rFVIIa group), while the remaining 102 patients did not (non-rFVIIa group). Perioperative bleeding and transfusions, postoperative 30-day mortality, and adverse events (AEs) were analyzed in 29 propensity score-matched pairs. Results: Before surgery, the rFVIIa group demonstrated a greater number of shocks (p=0.019), higher JapanSCORE II mortality rate (p=0.033), low platelet count (p=0.015) and fibrinogen (p<0.001) level, prolonged activated partial thromboplastin time (aPTT) (p=0.005) and prothrombin time international normalized ratio (PT-INR) (p=0.006), and longer aortic cross clamp time (p=0.049). Postoperative bleeding, transfusion, 30-day mortality, and AEs were comparable between the groups both in the entire-unmatched cohort and propensity score matching cohort. Conclusion: Preoperative shock, higher JapanSCORE II mortality rates, low platelet and fibrinogen levels, prolonged aPTT and PT-INR, and longer aortic clamping time might be risk factors for excessive bleeding and indicate the need for rFVIIa treatment. The present study suggests that rFVIIa can be safely used to address critical and continuous bleeding in spite of adequate transfusion and supplementation of other coagulation factors in aortic surgery under HCA, without an increase in 30-day mortality and AEs.

Post-cardiotomy pericardial effusion and postoperative atrial fibrillation risk.

Postoperative atrial fibrillation is a poor prognostic factor associated with increased mortality rates. Patients experiencing significant pericardial effusion develop postoperative atrial fibrillation; however, little is explored about the association between postoperative atrial fibrillation and post-cardiotomy pericardial effusion. This retrospective, single-center study included adult patients who underwent cardiovascular surgery via median sternotomy from January 2016 to December 2019. Patients who underwent routine postoperative computed tomography at 7 ± 3 days after surgery (n = 294) were included. Pericardial effusion was measured at the thickest point. Patients were classified into those with (n = 127) and without (n = 167) postoperative atrial fibrillation. The association of pericardial effusion with other factors was evaluated. A possible confounder-adjusted logistic regression analysis after multiple imputation was performed to obtain odds ratios for postoperative atrial fibrillation using previously published risk factors. Age, intraoperative bleeding volume, and pericardial effusion size were all significantly higher in the group with postoperative atrial fibrillation. Multivariate logistic regression after multiple imputation revealed that age, intraoperative bleeding volume, and postoperative pericardial effusion were significantly associated with postoperative atrial fibrillation. Our findings suggest that post-cardiotomy pericardial effusion is associated with postoperative atrial fibrillation. However, the causality remains unknown, making further studies mandatory.

Comparing Conscious Sedation With Regional Anesthesia Versus General Anesthesia in Minimally Invasive Mitral Valve Surgery With Right-Sided Minithoracotomy: A Retrospective Study.

OBJECTIVES: The aims of the present study were to evaluate and compare the safety and feasibility, including hospitalization, intensive care unit (ICU) stay, frequency of conversion to general anesthesia (GA), pH, PaCO2, and PaO2, of selected patients who underwent minimally invasive mitral valve surgery (MIMVS) via a right minithoracotomy under conscious sedation (CS) to avoid GA. The authors also aimed to evaluate the perioperative management of spontaneous breathing. DESIGN: A retrospective, observational study. SETTING: Single-center. PARTICIPANTS: This study enrolled 101 patients who underwent MIMVS under CS or GA. INTERVENTIONS: The patients who underwent MIMVS were managed under CS or GA according to indication criteria. MEASUREMENTS AND MAIN RESULTS: ICU stay (p = 0.010), postoperative time until first fluid intake (p < 0.0001), and duration of mechanical ventilation (p = 0.004) were shorter in the CS group than in the GA group. No patients converted to GA from CS. PaCO2 during cardiopulmonary bypass (CPB) in the CS group was significantly lower than that in the GA group. However, PaCO2 at the termination of CPB in the CS group was significantly higher than that in the GA group. CONCLUSIONS: In the CS group, advanced-age patients with comorbidities underwent mitral surgery without postoperative complications. The authors' findings suggested that MIMVS under CS could be a potentially less-invasive method, providing a quicker recovery than MIMVS under GA.

Accidental hypothermia: characteristics, outcomes, and prognostic factors-A nationwide observational study in Japan (Hypothermia study 2018 and 2019).

AIM: This study describes the clinical characteristics and outcomes as well as the prognostic factors of patients with accidental hypothermia (AH) using Japan's nationwide registry data. METHODS: The Hypothermia study 2018 and 2019, which included patients aged 18 years or older with a body temperature of 35°C or less, was a multicenter registry conducted at 87 and 89 institutions throughout Japan, with data collected from December 2018 to February 2019 and December 2019 to February 2020, respectively. RESULTS: In total, 1363 patients were enrolled in the registry, of which 1194 were analyzed in this study. The median (interquartile range) age was 79 (68-87) years, and the median (interquartile range) body temperature at the emergency department was 30.8°C (28.4-33.6°C). Forty-three percent of patients with AH had a mild condition, 35.2% moderate, and 21.9% severe. AH occurred in an indoor setting in 73.4% and was caused by acute medical illness in 49.3% of patients. A total of 101 (8.5%) patients suffered from cardiopulmonary arrest on arrival at the hospital. The overall 30-day mortality rate was 24.5%, the median (interquartile range) intensive care unit stay was 4 (2-7) days, and the median (interquartile range) hospital stay was 13 (4-27) days. In the multivariable logistic analysis, the prognostic factors were age (≥75 years old), male, activities of daily living (needing total assistance), cause of AH (trauma, alcohol), Glasgow Coma Scale score, and potassium level (>5.5 mEq/L). CONCLUSION: The mortality rate of AH was 24.5% in Japan. The prognostic factors developed in this study may be useful for the early prediction, prevention, and awareness of severe AH.

Population Attributable Fractions of Modifiable Risk Factors for Nonsyndromic Orofacial Clefts: A Prospective Cohort Study From the Japan Environment and Children's Study.

BACKGROUND: Population impact of modifiable risk factors on orofacial clefts is still unknown. This study aimed to estimate population attributable fractions (PAFs) of modifiable risk factors for nonsyndromic cleft lip with or without cleft palate (CL±P) and cleft palate only (CP) in Japan. METHODS: We conducted a prospective cohort study using data from the Japan Environment and Children's Study, which recruited pregnant women from 2011 to 2014. We estimated the PAFs of maternal alcohol consumption, psychological distress, maternal active and passive smoking, abnormal body mass index (BMI) (<18.5 and ≥25 kg/m2), and non-use of a folic acid supplement during pregnancy for nonsyndromic CL±P and CP in babies. RESULTS: A total of 94,174 pairs of pregnant women and their single babies were included. Among them, there were 146 nonsyndromic CL±P cases and 41 nonsyndromic CP cases. The combined adjusted PAF for CL±P of the modifiable risk factors excluding maternal alcohol consumption was 34.3%. Only maternal alcohol consumption was not associated with CL±P risk. The adjusted PAFs for CL±P of psychological distress, maternal active and passive smoking, abnormal BMI, and non-use of a folic acid supplement were 1.4% (95% confidence interval [CI], -10.7 to 15.1%), 9.9% (95% CI, -7.0 to 26.9%), 10.8% (95% CI, -9.9 to 30.3%), 2.4% (95% CI, -7.5 to 14.0%), and 15.1% (95% CI, -17.8 to 41.0%), respectively. We could not obtain PAFs for CP due to the small sample size. CONCLUSIONS: We reported the population impact of the modifiable risk factors on CL±P, but not CP. This study might be useful in planning the primary prevention of CL±P.

Identifying a risk score for childhood obesity based on predictors identified in pregnant women and 1-year-old infants: An analysis of the data of the Hokkaido Study on Environment and Children's Health.

This study aimed to construct a childhood obesity risk index based on predictors identified in pregnant women and 1-yr-old infants. The primary outcome was an identified obesity index of > 20% at 6-8 yr of age. Of a total sample size of 6,846 mother-child pairs, 80% and 20% were randomly allocated to the derivation and validation cohorts, respectively. For the derivation cohort, univariate and multivariate logistic regression analyses of data were conducted to identify the final predictors to determine the childhood obesity risk score algorithm. These included pre-pregnancy body mass index (BMI), child's gender, smoking during pregnancy, education, and obesity index at one yr of age. The ß coefficients for categories of predictor variables were each divided by the smallest value among them. The quotient was rounded off to the integer and assigned to the risk score, and a value of zero was assigned to reference categories. A total risk score was calculated for each individual. A cutoff point ≥ 16 had 22.2% and 21.8% positive predictive values in the derivation and validation cohorts, respectively. In conclusion, the childhood obesity risk score algorithm was constructed based on generic predictors that can be easily obtained from maternal and child health handbooks.

Acute myocardial infarction and stoke after the enactment of smoke-free legislation in public places in Bibai city: data analysis of hospital admissions and ambulance transports.

Public smoke-free legislation has been in place since July 2016 in a small city (Bibai) in Hokkaido (Japan); the effects of public smoke-free legislation in small cities in Japan on cardiovascular and cerebrovascular events have not been fully investigated. Monthly numbers of acute myocardial infarctions (AMIs) and stroke admissions were obtained from medical records, and the adjacent area, Naka-Sorachi, was used as a control region. According to the results of the Poisson regression, significant direct outcomes after the enactment of smoke-free legislation in Bibai city were not observed. After the implementation of the smoke-free legislation, the average monthly admission rates per population and risk ratios for AMI, stroke, and the combined outcome (AMI plus stroke) decreased in the Bibai region but increased in the control region (Naka-Sorachi), although there was no statistically significant difference between the two regions. However, significant interactions between the region (Bibai or Naka-Sorachi) and period (before or after the legislation) for stroke and the combined outcome were noted. Although a direct admission effect was not observed, the significant interaction indicated that Bibai had a decreasing trend in emergency admissions compared with the control region (Naka-Sorachi). Public smoke-free legislation in small cities may also decrease cardiovascular events.

Impacts of Diabetes and an SGLT2 Inhibitor on the Glomerular Number and Volume in db/db Mice, as Estimated by Synchrotron Radiation Micro-CT at SPring-8.

BACKGROUND: Recent large-scale clinical studies demonstrate that sodium-glucose cotransporter 2 (SGLT2) inhibitors protect the diabetic kidney. However, clinical and animal studies have not shown the changes of the total glomeruli in the whole kidney treated with SGLT2 inhibitors. METHODS: We performed computed tomography (CT) imaging on mice using synchrotron radiation to investigate the impact of luseogliflozin, a SGLT2 inhibitor, on the number and volume of glomeruli in the whole kidney. FINDINGS: We did not observe a significant difference in the total glomerular number (Nglom) among mice. Luseogliflozin redistributed the number of glomeruli in different regions, accompanied by the normalization of diabetes-augmented renal volume (Vkidney). Diabetic db/db mice had a larger glomerular volume in the mid-cortex than did control db/m mice, and luseogliflozin increased the glomerular volume in all renal cortical zones of the whole kidney in db/db mice. According to the multivariate regression analysis, hemoglobin A1c level was the most relevant determinant of Vkidney, not Nglom or mean glomerular volume (Vglom), indicating that hyperglycemia induced renal (tubular) hypertrophy, but not glomerular enlargement. Luseogliflozin increased hypoxia in the juxtamedullary region, sustained upregulated renal renin expression and plasma renin activity, and failed to decrease albuminuria by downregulating megalin in db/db mice. INTERPRETATION: Based on our findings, SGLT2 inhibitors may alter glomerular distribution and size in addition to their glucose-lowering effects, presumably by affecting oxygen metabolism and humoral factors. FUND: Funding for this research was provided by The Japan Society for the Promotion of Science, the Japan Diabetes Foundation, and Asahikawa Medical University.

A prospective cohort study of insomnia and chronic kidney disease in Japanese workers.

PURPOSE: The role of insomnia in chronic kidney disease (CKD) is controversial. To date, there have been no prospective studies investigating insomnia, CKD and the effect of shift work. We assessed insomnia and CKD risk in a prospective, occupational cohort study. METHODS: A total of 3600 participants with normal kidney function were followed for an average of 4.4 years. Insomnia was assessed using the Athens Insomnia Scale (AIS). CKD was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m2 at the first health examination. Cox proportional hazard regression models were used to estimate hazard ratios with 95% confidence intervals of insomnia for CKD development. RESULTS: A total of 182 CKD cases were identified. After adjustment for potential confounders, we did not observe an association between insomnia (AIS score ≥6) and CKD. However, the AIS item of awakening during the night was associated with a significantly increased CKD risk (hazard ratio = 3.10, 95% confidence interval 1.68-5.30). In further analyses, having difficulty with sleep induction was associated with an increased CKD risk among shift workers (hazard ratio = 3.34, 95% confidence interval 1.22-8.31). This association was not present among non-shift workers. CONCLUSIONS: Awakening during the night is associated with a moderately increased CKD risk.

Demographic, behavioral, dietary, and socioeconomic characteristics related to persistent organic pollutants and mercury levels in pregnant women in Japan.

Persistent organic pollutants and mercury are known environmental chemicals that have been found to be ubiquitous in not only the environment but also in humans, including women of reproductive age. The purpose of this study was to evaluate the association between personal lifestyle characteristics and environmental chemical levels during the perinatal period in the general Japanese population. This study targeted 322 pregnant women enrolled in the Hokkaido Study on Environment and Children's Health. Each participant completed a self-administered questionnaire and a food-frequency questionnaire to obtain relevant information on parental demographic, behavioral, dietary, and socioeconomic characteristics. In total, 58 non-dioxin-like polychlorinated biphenyls, 17 dibenzo-p-dioxins and -dibenzofuran, and 12 dioxin-like polychlorinated biphenyls congeners, perfluorooctane sulfonate, perfluorooctanoic acid, and mercury were measured in maternal samples taken during the perinatal period. Linear regression models were constructed against potential related factors for each chemical concentration. Most concentrations of environmental chemicals were correlated with the presence of other environmental chemicals, especially in the case of non-dioxin-like polychlorinated biphenyls and, polychlorinated dibenzo-p-dioxins and -dibezofurans and dioxin-like polychlorinated biphenyls which had similar exposure sources and persistence in the body. Maternal smoking and alcohol habits, fish and beef intake and household income were significantly associated with concentrations of environmental chemicals. These results suggest that different lifestyle patterns relate to varying exposure to environmental chemicals.

Late gadolinium enhancement on cardiac magnetic resonance represents the depolarizing and repolarizing electrically damaged foci causing malignant ventricular arrhythmia in hypertrophic cardiomyopathy.

BACKGROUND: The presence of a myocardial scar detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) has been described as a predictor of all-cause mortality in hypertrophic cardiomyopathy (HCM). However, the detailed spatial relationship between LGE site and electrical abnormality is unclear in high-risk HCM with malignant arrhythmia. OBJECTIVE: The purpose of this study was to elucidate the detailed relationship between the site on CMR imaging and the electrically damaged site, a potential origin of ventricular arrhythmias in patients with HCM. METHODS: Fifty consecutive HCM patients underwent contrast-enhanced CMR. Of those patients, 18 patients with ventricular tachycardia underwent electrophysiology study including endocardial mapping of the left ventricle (LV). The LGE area was calculated at 12 different LV sites: anterior, lateral, posterior, and septal segments of the basal, middle, and apical portions. At each LV site, the bipolar electrogram, effective refractory period (ERP), and monophasic action potential were recorded. RESULTS: LGE-positive segments demonstrated a significantly lower amplitude (4.0 ± 2.8 mV vs 7.3 ± 3.6 mV; P < .001), longer duration (54.7 ± 17.8 vs 40.6 ± 7.8 ms; P < .001), longer ERP (320 ± 42 ms vs 284 ± 37 ms; P = .001), and longer monophasic action potential duration measured at 90% repolarization (321 ± 19 ms vs 283 ± 25 ms; P < .001) than did LGE-negative segments. The LGE area negatively correlated with the amplitude (r = -0.59; P < .001) and positively correlated with the duration (r = 0.64; P < .001), ERP (r = 0.44; P < .001), and action potential duration measured at 90% repolarization (r = 0.63; P < .001). All the observed VTs originated from LGE-positive segments. CONCLUSION: The spatial distribution of LGE significantly correlates with depolarizing and repolarizing electrical damage in high-risk HCM with malignant ventricular arrhythmia.

Biomonitoring of mercury, cadmium, and lead exposure in Japanese children: a cross-sectional study.

OBJECTIVES: To measure current Hg, Cd, and Pb exposure in Japanese children, and to estimate dietary intakes of foods responsible for high body burden. METHODS: Blood, hair, and urine samples were collected from 9 to 10-year-old 229 children in Asahikawa and measured for Hg, Cd, and Pb in these matrices. Diet history questionnaire was used to estimate intake of marine foods and other food items. Hg level was measured by cold vapor atomic absorption spectrometry. Cd and Pb levels were determined with inductively coupled plasma mass spectrometry. RESULTS: Geometric mean (GM) of blood Hg, Cd, and Pb was 4.55 µg/L, 0.34 µg/L, and 0.96 µg/dL, respectively. Urinary Cd level was 0.34 µg/g creatinine (GM) and hair Hg was 1.31 µg/g (GM). Approximately one-third (35%) of blood samples had Hg level above the U.S. EPA reference dose (RfD; 5.8 µg/L). Hair Hg level exceeded U.S. EPA RfD (1.2 µg/g) in 59 % samples. Children in the upper quartile of blood Hg level had significantly higher intake of large predatory fish species compared to those in the lower quartile of blood Hg. CONCLUSIONS: Those with high blood Hg level may be explained by more frequent intake of big predatory fish. Cd and Pb exposure is generally low among Japanese children. As no safety margin exists for Pb exposure and high exposure to MeHg is noted in Japanese population; periodic biomonitoring and potential health risk assessment should continue in high-risk populations, notably among children.

Prognostic factors in 105 Japanese cases of mycosis fungoides and Sézary syndrome: clusterin expression as a novel prognostic factor.

BACKGROUND: The analysis of prognostic factors in Japanese cases of cutaneous T-cell lymphoma (CTCL) is scarce. Clusterin is a ubiquitous 80kDa heterodimeric glycoprotein expressed on tumor cells of systemic and primary cutaneous anaplastic large cell lymphoma. The expression of clusterin in mycosis fungoides (MF) and Sézary syndrome (SS) has only been sporadically reported in a small number of cases. OBJECTIVE: To determine the long-term prognosis of Japanese patients with MF and SS, to identify clinical and pathological factors predictive of survival, and to evaluate the prognostic significance of the International Society for Cutaneous Lymphomas (ISCL) revised staging system (2007). METHODS: We performed a retrospective cohort study of 105 Japanese patients with MF and SS managed at the Department of Dermatology Asahikawa Medical University from 1976 to 2011. Formalin-fixed, paraffin-embedded sections of MF and SS were immunostained for clusterin, CD30, and Ki-67. RESULTS: No statistically significant difference in survival was found between stages IA-IIA and IIIA patients. The significant prognostic factors in the univariate analysis were higher age, TNMB classification, clinical staging, performance status, increased serum LDH level, dermal Ki-67-positive cells, and clusterin expression. In the multivariate analysis, T classification, extracutaneous disease, increased serum LDH level, clusterin expression, and performance status were the significant independent prognostic factors. CONCLUSION: Japanese stage IIIA MF/SS patients contain a subpopulation with a favorable prognosis. The most significant prognostic factor for survival of MF and SS was the presence of extracutaneous disease. Clusterin expression was shown to be a novel unfavorable prognostic factor.

Genetic association of aromatic hydrocarbon receptor (AHR) and cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) polymorphisms with dioxin blood concentrations among pregnant Japanese women.

Dioxins are metabolized by cytochrome P450, family 1 (CYP1) via the aromatic hydrocarbon receptor (AHR). We determined whether different blood dioxin concentrations are associated with polymorphisms in AHR (dbSNP ID: rs2066853), AHR repressor (AHRR; rs2292596), CYP1 subfamily A polypeptide 1 (CYP1A1; rs4646903 and rs1048963), CYP1 subfamily A polypeptide 2 (CYP1A2; rs762551), and CYP1 subfamily B polypeptide 1 (CYP1B1; rs1056836) in pregnant Japanese women. These six polymorphisms were detected in 421 healthy pregnant Japanese women. Differences in dioxin exposure concentrations in maternal blood among the genotypes were investigated. Comparisons among the GG, GA, and AA genotypes of AHR showed a significant difference (genotype model: P=0.016 for the mono-ortho polychlorinated biphenyl concentrations and toxicity equivalence quantities [TEQs]). Second, we found a significant association with the dominant genotype model ([TT+TC] vs. CC: P=0.048 for the polychlorinated dibenzo-p-dioxin TEQs; P=0.035 for polychlorinated dibenzofuran TEQs) of CYP1A1 (rs4646903). No significant differences were found among blood dioxin concentrations and polymorphisms in AHRR, CYP1A1 (rs1048963), CYP1A2, and CYP1B1. Thus, polymorphisms in AHR and CYP1A1 (rs4646903) were associated with maternal dioxin concentrations. However, differences in blood dioxin concentrations were relatively low.