Neurodevelopmental associations of prenatal and postnatal methylmercury exposure among first-grade children in the Kinan region, Japan.

The most severe effects of methylmercury (MeHg) exposure during child development are thought to result from exposure during fetal life and childhood. However, comparing the neurodevelopmental effects of prenatal and postnatal MeHg exposure (PreMeHg and PostMeHg, respectively) remains unclear. We aimed to investigate the associations between neurodevelopmental indicators and PreMeHg or PostMeHg. The participants were 134 children in the first grade of elementary schools aged 7-8 years from the Kinan region, an area with high consumption of MeHg-rich whales and tunas in Japan. We measured MeHg levels in preserved umbilical cord tissues and total mercury (T-Hg) levels in children's hair to estimate PreMeHg and PostMeHg levels, respectively. Neuropsychological (intelligence quotient testing and Boston Naming Test) and neurophysiological (brainstem auditory evoked potential [BAEP], visual evoked potential [VEP], and color vision tests) studies were performed to evaluate the neurodevelopmental status. Multiple regression analyses were conducted according to sex. The geometric mean MeHg levels in preserved umbilical cord tissues and T-Hg levels in children's hair were 0.11 µg/g and 2.94 µg/g, respectively. Neither PreMeHg nor PostMeHg was related to neuropsychological indicators. Some associations between MeHg exposure and neurophysiological results were observed only in boys. N145 latency in VEPs was significantly prolonged with increasing PreMeHg (ß: 12.01, 95% confidence interval [CI]: 0.648, 23.38). The III-V interpeak intervals in BAEP were significantly prolonged with increasing PreMeHg or PostMeHg (ß [95% CI]: 0.142 [0.041, 0.243] and 0.159 [0.052, 0.265], respectively). After adjusting for PreMeHg, the association between PostMeHg and BAEP latencies disappeared. In conclusion, the latency in the auditory and visual pathways was significantly prolonged with increasing PreMeHg in boys. These findings suggest that male fetuses may be more susceptible to MeHg exposure.

Cesarean delivery rates for overall and multiple pregnancies in Japan: A descriptive study using nationwide health insurance claims data.

AIM: Due to the lack of national perinatal registries, population-wide descriptive statistics on cesarean deliveries in Japan are unknown. We aim to describe cesarean deliveries for overall and multiple pregnancies using the Japan National Database of health insurance claims. METHODS: We calculated the national and prefectural cesarean delivery rates for overall and multiple pregnancies in 2014. We described maternal morbidities (e.g., blood transfusion) and the place and type of the institutions providing prenatal and perinatal care. RESULTS: The national cesarean delivery rates were 18.6% overall and 82.7% for women with multiple pregnancies. Prefectural cesarean delivery rates for overall and multiple pregnancies varied from 12.5% to 24.2% and from 49.2% to 100%, respectively, showing a moderate positive correlation (r = 0.59, p < 0.001). Overall, 1.4% of cesarean patients received an allogeneic blood transfusion, compared to 3.2% for those with multiple pregnancies. In addition, 65.9% of overall cesarean deliveries occurred at hospitals with ≥20 beds, whereas 94.6% of cesarean patients with multiple pregnancies delivered at hospitals. Older patients were more likely to receive their cesarean section at a different institution than their first visit within the same prefecture, but trans-prefectural movement during pregnancy covered by health insurance was most frequent among those in their early thirties: 7.0% overall and 10.7% for multiple pregnancies. CONCLUSIONS: The overall cesarean delivery rate in Japan was optimal, but the rate was high for multiple pregnancies, with large regional differences. Data on patient movement across institutions and areas would help to improve the perinatal care system.

Plasma and red blood cells distribution of total mercury, inorganic mercury, and selenium in maternal and cord blood from a group of Japanese women.

Fetuses are a high-risk group for methylmercury (MeHg) exposure. The main objective of this study was to compare the characteristic profiles of total mercury (THg), inorganic mercury (IHg), MeHg, and selenium in plasma and red blood cells (RBCs) between maternal and cord blood at parturition collected from a group of Japanese women. Furthermore, correlations of THg in RBCs, which is a biomarker of MeHg, and THg in plasma, which is an IHg exposure biomarker, were examined in maternal and cord blood. Fifty-five pairs of maternal and cord blood samples obtained at parturition were collected from pregnant women in Fukuoka, Japan. THg in RBCs and plasma were significant correlated between maternal and cord blood. THg in RBCs was 13.9 ng/mL for cord and 9.16 ng/mL for maternal blood, with a cord:maternal RBCs ratio for THg of 1.58, suggesting that MeHg is actively transferred from the mother to the fetus via the placenta. THg in plasma showed a positive correlation with THg in RBCs for maternal and cord blood. This result suggests that measuring THg in plasma can overestimate the exposure level to IHg in fish-eating populations. The percentages of IHg in cord plasma and RBCs were 31% and 1.7%, respectively, and those in maternal plasma and RBCs were 46% and 5.9%, respectively. These results suggest that cord blood is rich in MeHg and can easily transfer to the fetal brain. Selenium in cord plasma was 67 ng/mL and that in maternal plasma was 97 ng/mL, with a cord:maternal plasma ratio for Se of 0.69, suggesting that the protective effects of Se against MeHg toxicity in fetuses may be weaker than those expected in adult mothers.

Associations between blood arsenic and urinary arsenic species concentrations as an exposure characterization tool.

Blood arsenic has various toxicities including carcinogenicity, but urinary concentrations are often substituted to determine the exposure level. Since there is little information on the relation of urinary arsenic species to blood arsenic, the aim was to investigate relationships between blood total arsenic (T-As) and the urinary species adjusted by creatinine and specific gravity (SG). Blood and spot urine samples were collected from 109 Japanese subjects aged 18-66 years without occupational exposure. Positive correlations of blood T-As (median, 3.49 µg/L) with urinary creatinine-adjusted and SG-adjusted T-As and arsenobetaine were statistically significant and greater than those with the unadjusted ones. The magnitude of associations of blood T-As with creatinine-adjusted arsenic species was significantly larger than those with unadjusted or SG-adjusted ones. Most of the correlation coefficients among urinary arsenic species concentrations were significant in three adjustment methods, but there was not a significant correlation between monomethylarsonic acid and arsenobetaine after urinary creatinine and SG corrections. Given multiple regression analysis, plasma T-As concentrations showed significant relations to creatinine-adjusted T-As, dimethylarsinic acid, and arsenobetaine concentrations, but erythrocyte T-As did hardly reflect the variation of urinary arsenic species. In conclusion, creatinine-adjusted arsenic concentrations are suggested to be the most appropriate predictor of blood T-As; by contrast, use of the urinary unadjusted arsenic concentration may result in a misleading interpretation of inorganic arsenic toxicity because the associations between inorganic and organic arsenic species based on the unadjusted concentration were mutually close. Plasma T-As appeared to be the best indicator of low-level exposure in blood samples.

Prenatal and postnatal lead exposures and intellectual development among 12-year-old Japanese children.

BACKGROUND: Low-level lead exposure during childhood is associated with deficit in child IQ. However, the association between prenatal lead exposure and child IQ remains inconsistent. The objective of our study was to examine the association between prenatal/postnatal lead exposure and child IQ at the age of 12. METHODS: We obtained data pertaining to cord-blood and child-blood lead levels and IQ for 286 children from a prospective birth cohort study (Tohoku Study of Child Development). IQ was assessed using the Wechsler Intelligence Scale for Children-Fourth Edition. Simultaneously, the Boston Naming Test (BNT) was used to assess the children's language ability. RESULTS: The median lead level in the cord blood was 0.8 µg/dL (5th-95th percentiles, 0.4-1.4 µg/dL), and that in the blood of 12-year-old children was 0.7 µg/dL (0.4-1.1 µg/dL). IQ and BNT scores were significantly lower in boys than in girls; therefore, multiple regression analysis was conducted separately for boys and girls. Among boys, IQ was associated with child-blood lead (B = -16.362, p = 0.033) but not cord-blood lead (B = -6.844, p = 0.309). When boys were divided into four groups according to the child-blood lead levels, there was a significant decreasing trend for IQ. The score with cues of the BNT was associated with both cord-blood (B = -5.893, p = 0.025) and child-blood (B = -7.108, p = 0.022) lead concentrations in boys. Among girls, there was no significant association of the outcomes with cord-blood or child-blood lead level. CONCLUSIONS: These findings suggest that postnatal lead exposure adversely affects the intellectual ability in boys. Furthermore, the language ability is sensitive to prenatal/postnatal lead exposure in boys.

Clinical Assessment of Scleral Canal Area in Glaucoma Using Spectral-Domain Optical Coherence Tomography.

PURPOSE: To investigate anterior scleral canal (ASC) area in the eyes with glaucoma using spectral-domain optical coherence tomography (SDOCT). DESIGN: Cross-sectional study. METHODS: This study included 206 eyes of 103 patients with glaucoma, classified as 66 eyes of 33 patients with unilateral glaucoma and 140 eyes of 70 patients with bilateral glaucoma. Radial scan enhanced depth imaging SDOCT centered on the optic disc was performed, and parameters that present ASC area such as ASC opening and the largest ASC area were obtained in each eye. The largest ASC area was the largest cross-sectional area of the ASC region identified between the ASC opening and anterior lamina cribrosa insertion. These parameters were compared between eyes with and without glaucoma in unilateral glaucoma, and eyes with worse and better visual field defect (VFD) in bilateral glaucoma. RESULTS: In the patients with unilateral glaucoma, ASC opening and largest ASC area were significantly larger in the eyes with glaucoma than in those without glaucoma (both P < .001). In bilateral glaucoma, these parameters were significantly larger in the eyes with worse VFD than in those with better VFD (P = .0080 and P = .0018, respectively). Intereye differences of the ASC parameters in the glaucoma patients were significantly greater than that in the normal subjects. CONCLUSIONS: Significantly larger ASC area was first observed in the living human eyes with glaucoma compared to the normal eyes. Further longitudinal studies are required to determine if the ASC area is useful in the prevention and treatment of glaucoma.

Dose-dependent associations between prenatal caffeine consumption and small for gestational age, preterm birth, and reduced birthweight in the Japan Environment and Children's Study.

BACKGROUND: Few previous studies have investigated the association between prenatal caffeine intake and birth size (small for gestational age [SGA], preterm birth, and birthweight Z-score) in Japan. OBJECTIVES: We examined the dose-dependency of this association (prenatal caffeine consumption and birth size) as part of the Japan Environment and Children's Study. METHODS: A prospective birth cohort included 94 876 fetuses in Japan. Participants were enrolled between January 2011 and March 2014. Adjusted multiple linear regression and Cox regression models were used to examine the association between prenatal caffeine levels and infant birth size. RESULTS: The median estimated caffeine consumption during pregnancy was 125.5 mg/day, as determined by self-administered questionnaires. There were 7252 SGA infants (7.6%) and 4281 preterm birth infants (4.5%). Compared with infants of mothers whose caffeine consumption during pregnancy was in the lowest quartile (4.2 to <86.4 mg/day), infants of mothers whose caffeine consumption was in the highest quartile 4 (205.5-5080.0 mg/day) were at an increased risk of SGA (relative risk [RR] 1.18, 95% confidence interval [CI] 1.10, 1.27), and at an increased risk of preterm birth at the second trimester of gestation (RR 1.94, 95% CI 1.12, 3.37), with a 0.32-day reduction in gestational age (95% CI -0.52, -0.12) and with a 0.07 reduction in birthweight Z-score observed (95% CI -0.09, -0.05). CONCLUSIONS: Prenatal caffeine consumption was associated with birth size. However, as the association between prenatal caffeine consumption and birth size was likely confounded by unpredicted potential factors, our confidence in the true causality of the association is moderate.

Hospital-based screening to detect patients with cadmium nephropathy in cadmium-polluted areas in Japan.

BACKGROUND: In health examinations for local inhabitants in cadmium-polluted areas, only healthy people are investigated, suggesting that patients with severe cadmium nephropathy or itai-itai disease may be overlooked. Therefore, we performed hospital-based screening to detect patients with cadmium nephropathy in two core medical institutes in cadmium-polluted areas in Akita prefecture, Japan. METHODS: Subjects for this screening were selected from patients aged 60 years or older with elevated serum creatinine levels and no definite renal diseases. We enrolled 35 subjects from a hospital in Odate city and 22 from a clinic in Kosaka town. Urinary ß2-microglobulin and blood and urinary cadmium levels were measured. RESULTS: The criteria for renal tubular dysfunction and the over-accumulation of cadmium were set as a urinary ß2-microglobulin level higher than 10,000 µg/g cr. and a blood cadmium level higher than 6 µg/L or urinary cadmium level higher than 10 µg/g cr., respectively. Subjects who fulfilled both criteria were diagnosed with cadmium nephropathy. Six out of 57 patients (10.5% of all subjects) had cadmium nephropathy. CONCLUSIONS: This hospital-based screening is a very effective strategy for detecting patients with cadmium nephropathy in cadmium-polluted areas, playing a complementary role in health examinations for local inhabitants. REGISTRATION NUMBER: No. 6, date of registration: 6 June, 2010 (Akita Rosai Hospital), and No. 1117, date of registration: 26 December, 2013 (Akita University).

Associations of environmental exposures to methylmercury and selenium with female infertility: A case-control study.

BACKGROUND: Methylmercury exposure is a common health risk resulting from daily fish intake. However, studies addressing the link between methylmercury and infertility are limited and also inconsistent. In addition, no previous epidemiological studies have accounted for the interaction between methylmercury and selenium. We aimed to investigate the association between environmental exposures to metals and female fertility. METHODS: This case-control study included 98 infertile women receiving fertility treatment (infertile group) and 43 female workers in their thirties (control group) who provided blood samples and returned a questionnaire on lifestyles and dietary characteristics. Blood levels of mercury, lead, cadmium, arsenic, manganese, zinc, and selenium were compared between the groups. Spearman correlation analyses between anti-Müllerian hormone and the metals were conducted. RESULTS: The mean selenium level in blood (±â€¯SD) and the selenium/mercury molar ratio were significantly lower in the infertile group (189 ±â€¯25 µg/L and 94.6 ±â€¯44.3, respectively) than in the control group (200 ±â€¯25 µg/L and 118.4 ±â€¯70.5). By contrast, blood mercury levels after adjusting for blood selenium and age were significantly higher in the infertile group than in the control group. Multiple logistic regression analyses with the adjustment for the other metals and potential confounders confirmed significant associations of infertility with elevated mercury and reduced selenium levels. No significant correlations were observed between anti-Müllerian hormone and metals. CONCLUSIONS: Methylmercury and selenium exposures appear to have adverse and protective effects on female fertility, respectively. This is the first report to suggest the antagonistic interaction between methylmercury and selenium in relation to human female fertility.

[Mercury as a Global Pollutant and Mercury Exposure Assessment and Health Effects].

Mercury and its compounds are classified into three main groups: metallic mercury (Hg0), inorganic mercury (Hg2+), and organic mercury (methyl mercury: CH3Hg+, etc.). Metallic mercury is the only metal that is liquid at ambient temperature and normal pressure, which readily forms an amalgam with other metals. Therefore, mercury has long been used for refining various metals, and mercury amalgam has been used for dental treatment. Mercury has also been used in measuring instruments such as thermometers, barometers and blood pressure monitors, as well as electric appliances such as lighting equipment and dry batteries. Large amounts of metallic mercury are still used in other countries as a catalyst in the production of caustic soda by electrolysis. In addition, mercury compounds have been used in various chemicals such as mercurochrome, agricultural chemicals, and mildew-proofing agents. However, the use of mercury has also caused health problems for people. Minamata disease in Japan is a typical example. Also, since mercury is highly volatile, it is discharged as a product of industrial activities or derived from volcanoes, and it has been concluded on the basis of the findings of the United Nations Environment Program (UNEP) that it is circulating globally. Therefore, with the aim of establishing an internationally legally binding treaty for the regulation of mercury use to reduce risk, an intergovernmental negotiating committee was established in 2009. Japan actively contributed to this negotiation owing to its experience with Minamata disease, which led to the Convention on the regulation of mercury use being discharged as the "Minamata Convention on Mercury" and the treaty came into force on August 16, 2017. In this review, we introduce 1) the Global Mercury Assessment by UNEP; 2) mercury kinetics, exposure assessment and toxicity of different chemical forms; 3) large-scale epidemics of methylmercury poisoning; 4) methylmercury exposure assessment and health survey in whale-eating populations; 5) elemental mercury exposure assessment and health survey of mercury mine workers in China.

Two-year follow-up of a randomized controlled trial: knowledge and reproductive outcome after online fertility education.

STUDY QUESTION: What are the long-term effects of fertility education on knowledge and reproductive outcome? SUMMARY ANSWER: Participants in the intervention group retained some knowledge after 2 years and the partnered women had a new child more quickly than the comparison group. WHAT IS KNOWN ALREADY: Fertility education improves knowledge, at least in the short-term. Attitudes toward childbearing and its timing can change after exposure to educational materials. STUDY DESIGN, SIZE, DURATION: Participants were recruited via an online social research panel. In the original randomized controlled trial (RCT), knowledge of reproductive-aged participants was assessed before (T1) and immediately after (T2) receiving one of three information brochures: fertility (intervention group), healthy pre-pregnancy (focused on intake of folic acid during pregnancy, control group 1), or family policies in Japan (childcare provision, control group 2). The present follow-up study was conducted 2 years later in January 2017 (T3) with the same participants. PARTICIPANTS/MATERIALS, SETTING, METHODS: Of the T1 participants (n = 1455), 383 men and 360 women (51%) responded to the T3 survey. Fertility knowledge measured with the Japanese version of the Cardiff Fertility Knowledge Scale (CFKS-J) and fertility status (e.g. new births, new medical consultations, and the timing of new birth) was assessed. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline (T1) characteristics of the T3 participants were well balanced between groups, but T3 participants were older, married, and more educated compared to those lost to follow-up. A repeated-measures analysis of variance showed significant knowledge gains among the intervention group from T1 to T3 (11.2% and 7.0% among men and women, respectively) but no significant change over time for the control groups. There were no differences between groups in the incidence of new births or new medical consultations. However, subgroup analysis showed that timing of new births was accelerated for partnered individuals in the intervention group. Specifically, the proportion of partnered participants at T1 who had a new birth in the first year subsequent to presentation of information was higher in the intervention group versus control group 1 (folic acid): 8.8% versus 1.4% (P = 0.09) among men and 10.6% versus 2.3% (P = 0.03) among women, respectively. The odds ratios (adjusted for age) were 7.8 (95% CI: 0.86-70.7) and 5.2 (95% CI: 1.09-25.0) among men and women, respectively. The timing of births and the proportion of new births during the 2-year follow-up period in the intervention group were similar to that of control group 2 (family policy). The incidence of new medical consultation was higher in the male intervention group (12.0%) than in male control group 2 (family policy, 1.5%, P = 0.04) but similar among women in all groups. LIMITATIONS REASONS FOR CAUTION: First, the high attrition rate may limit the generalizability of these findings for longer-term acquisition of fertility knowledge, especially when applied to younger people who were more likely to be lost to follow-up. Second, this is a 2-year follow-up study and the results may change in the longer-term. Finally, we relied on self-reported questionnaire data and there is a possibility that some women were unknowingly pregnant at T1 but this risk should be distributed equally in the three groups through randomization. WIDER IMPLICATIONS OF THE FINDINGS: Effects of one-time education were limited but retained beyond baseline levels. Importantly, education was found to potentially accelerate decision-making about achieving births in partnered subgroups compared to receiving healthy pre-pregnancy information. However, this finding should be confirmed in future stratified RCTs designed to evaluate effects in these subgroups. Follow-up 'booster' education sessions might help people retain knowledge and facilitate reproductive decisions for longer. In view of the high attrition rate, especially among young populations, novel educational strategies to retain young people in fertility education cohorts should be explored. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by National Center for Child Health and Development, the Daiwa Anglo-Japanese Foundation, Pfizer Health Research Foundation, and the Japan Society for the Promotion of Science. E.M. reports joint research funds from a public interest incorporated foundation '1 more Baby Ohendan.'

Health Impacts and Biomarkers of Prenatal Exposure to Methylmercury: Lessons from Minamata, Japan.

The main chemical forms of mercury are elemental mercury, inorganic divalent mercury, and methylmercury, which are metabolized in different ways and have differing toxic effects in humans. Among the various chemical forms of mercury, methylmercury is known to be particularly neurotoxic, and was identified as the cause of Minamata disease. It bioaccumulates in fish and shellfish via aquatic food webs, and fish and sea mammals at high trophic levels exhibit high mercury concentrations. Most human methylmercury exposure occurs through seafood consumption. Methylmercury easily penetrates the blood-brain barrier and so can affect the nervous system. Fetuses are known to be at particularly high risk of methylmercury exposure. In this review, we summarize the health effects and exposure assessment of methylmercury as follows: (1) methylmercury toxicity, (2) history and background of Minamata disease, (3) methylmercury pollution in the Minamata area according to analyses of preserved umbilical cords, (4) changes in the sex ratio in Minamata area, (5) neuropathology in fetuses, (6) kinetics of methylmercury in fetuses, (7) exposure assessment in fetuses.

Methylmercury Exposure and Developmental Outcomes in Tohoku Study of Child Development at 18 Months of Age.

Seafood is an important component in a healthy diet and may contain methylmercury or other contaminants. It is important to recognize the risks and benefits of consuming seafood. A longitudinal prospective birth cohort study has been conducted to clarify the effects of neurotoxicants on child development-the Tohoku Study of Child Development (TSCD) in Japan. TSCD comprises two cohorts; a polychlorinated biphenyls (PCB) cohort (urban area) and a methylmercury cohort (coastal area). Our previous results from the coastal area showed prenatal methylmercury exposure affected psychomotor development in 18-month-olds, and boys appear to be more vulnerable to the exposure than girls. In this report, we have added the urban area cohort and we reanalyzed the impact of prenatal exposure to methylmercury, which gave the same results as before. These findings suggest prenatal exposure to low levels methylmercury may have adverse effects on child development, especially in boys.

Brain methylmercury uptake in fetal, neonate, weanling, and adult rats.

Fetuses and neonates are known to be highly susceptible to methylmercury (MeHg) toxicity, but little is known about the relative uptake of MeHg from blood to the developing brain. We measured time-course changes in mercury (Hg) concentrations in the brain of fetal, neonate, weanling, and adult rats after an injection of 0.08 µg (0.4 nmol) Hg/g MeHg. In the prenatal experiment, MeHg was subcutaneously injected to pregnant dams on embryonic days 17, 18, 18.5, 19, 19.5, or 20, and Hg concentrations in tissues were measured in both mothers and fetuses on embryonic day 21 (1 day before parturition). Brain Hg levels in fetuses peaked 2 days after injection and were approximately 1.5 times higher than in mothers. In the postnatal experiment, the same MeHg dose was injected subcutaneously to male rats on postnatal days 1 (neonates), 35 (weanlings), or 56 (adults). Mercury concentrations in tissues were measured 1, 2, 3, 4, 5, or 6 days after the injection. Brain Hg levels peaked most rapidly in neonates, and were approximately 1.5 times higher than levels in weanlings or adults. Throughout the examined period, peak Hg levels in the brain and the Hg brain/blood ratio 24 h after injection were highest in fetuses, followed by the levels in neonates, and decreased with life stage. These findings suggest that relatively higher brain MeHg uptake is an important factor in the vulnerability of fetuses and neonates to MeHg exposure.

Assessment of Cardiac Autonomic Function in Relation to Methylmercury Neurotoxicity.

After the European Food Safety Authority reviewed reports of methylmercury and heart rate variability (HRV) in 2012, the panel concluded that, although some studies of cardiac autonomy suggested an autonomic effect of methylmercury, the results were inconsistent among studies and the implications for health were unclear. In this study, we reconsider this association by adding a perspective on the physiological context. Cardiovascular rhythmicity is usually studied within different frequency domains of HRV. Three spectral components are usually detected; in humans these are centered at <0.04 Hz, 0.15 Hz (LF), and 0.3 Hz (HF). LF and HF (sympathetic and parasympathetic activities, respectively) are evaluated in terms of frequency and power. By searching PubMed, we identified 13 studies examining the effect of methylmercury exposure on HRV in human populations in the Faroe Islands, the Seychelles and other countries. Considering both reduced HRV and sympathodominant state (i.e., lower HF, higher LF, or higher LF/HF ratio) as autonomic abnormality, eight of them showed the significant association with methylmercury exposure. Five studies failed to demonstrate any significant association. In conclusion, these data suggest that increased methylmercury exposure was consistently associated with autonomic abnormality, though the influence of methylmercury on HRV (e.g., LF) might differ for prenatal and postnatal exposures. The results with HRV should be included in the risk characterization of methylmercury. The HRV parameters calculated by frequency domain analysis appear to be more sensitive to methylmercury exposure than those by time domain analysis.

[Dilemma of Environmental Health Research].

This article presents not only a brief overview of birth cohort studies focusing on environmental health in which the associations between health and environment were examined, but also a tentative plan to apply epidemiological data to benchmark dose calculation. According to the preceding studies, the checkpoints to be scrutinized when a result is not consistent with those of other researchers are as follows: (1) whether the study included all crucial confounders, (2) whether it included any exposure marker or confounder with a U-shaped dose-response curve, (3) whether the outcome measure was conducted by two or more examiners that might lead to measurement bias, (4) whether such examiners picked up information about exposure levels of the subjects before measuring the endpoints, and (5) whether subjects with different genetic factors were included in the analysis. In addition, (6) researchers conducting a children's study on developmental effects due to toxic substances must keep in mind that the impact of prenatal methylmercury exposure, independent of postnatal exposure, may continue for at least seven years. (7) When an environmental health research emphasizes to be population-based study, the levels of exposure to environmental chemical substances in developed countries with strict environmental regulations may be too low to examine a dose-response relationship for critical dose estimation. Such risk assessment should be carried out among the subjects with a wide range of exposure levels.

Mild oxidation-production of subnanometer-sized nanowindows of single wall carbon nanohorn.

The size control of nanowindows on the graphene walls is indispensable to develop innovative adsorption and separation technologies. As single wall carbon nanohorn (SWCNH) consists of graphene wall, the permeation of ions through the nanowindows can be evaluated with adsorption measurement. We regulated the nanowindow size by use of mild oxidation at 473-523 K for 20-70 h. The explicit low pressure adsorption hysteresis was observed in the N2 adsorption isotherms of thus-oxidized SWCNHs, suggesting the window size of 0.3-0.4 nm. Moreover, the aqueous phase adsorption measurement for Li+, Na+, K+, Rb+, and Cs+ indicates that the nanowindow size is smaller than about 0.37 nm, being close to the estimated size from N2 adsorption.

Focal Lamina Cribrosa Defect in Myopic Eyes With Nonprogressive Glaucomatous Visual Field Defect.

PURPOSE: To investigate focal lamina cribrosa (LC) defect that spatially correspond to the nonprogressive glaucomatous visual field defect (VFD) in myopic subjects. DESIGN: Case-control study. SUBJECTS: We included 159 myopic eyes with glaucomatous VFD under treatment and followed up for 7 years. METHODS: Serial enhanced-depth imaging spectral-domain optical coherence tomography B-scans of the optic discs were acquired at the end of the follow-up and reviewed for the LC defect. Nonprogressive VFD was defined as having ≤1 progressing point of Humphrey visual field, with a slope calculated using pointwise linear regression worse than -1.0 dB/year at P < .01. Eyes were classified as having either progressive or nonprogressive VFD, and associating factors were evaluated. RESULTS: Sixty-four subjects (40.3%) exhibited nonprogressive VFD with mean deviation change -0.06 ± 0.22 dB/year. Multivariate logistic regression analysis revealed that presence of LC defect was significantly associated with nonprogressive VFD (odds ratio, 3.96; P = .002). The location of LC defect corresponded spatially to the location of VFD. Nonprogressive eyes with LC defect exhibited lower baseline intraocular pressure (IOP) (16.6 mm Hg vs 21.0 mm Hg, P = .0030) and smaller percentage of IOP change (12.9% vs 30.5%, P < .0001) than those without LC defect, but greater myopic optic disc deformation (10.1 degrees vs 1.2 degrees in torsion angle, P < .0001). When the eyes with LC defect had higher baseline IOP, they exhibited progressive VFD. CONCLUSIONS: In myopic eyes, there are specific patters of LC defect that are suggested to be associated with nonprogressive glaucomatous VFD.

Cesarean section rates and local resources for perinatal care in Japan: A nationwide ecological study using the national database of health insurance claims.

AIM: High cesarean section (CS) rates in middle and high-income countries are partly attributable to provider factors, such as staffing patterns and fear of litigation. However, the relationship between CS rates and healthcare resources in the community is poorly understood. Official data on CS rates has been particularly limited in Japan. In this study, we examined nationwide CS statistics and evaluated the association with local resources for perinatal care. METHODS: We used accumulated data for CS registered in the Japan National Database of health insurance claims in 2013 and calculated crude and age-standardized CS rates at national and prefectural levels. We analyzed the ecological associations with supply of obstetricians and institution and scale of obstetric facilities using multiple regression models. RESULTS: There were 190 361 cesarean deliveries in 2013, giving an overall CS rate of 18.5% (elective CS rates 11.0%), which varied by prefecture from 14.0% to 25.6%. In multiple regression analyses, the areal number of obstetricians (standardized regression coefficient [ß] = -0.58), the proportion of births at small-scale institutions (ß = 0.36) and the number of beds at neonatal intensive care units per birth (ß = -0.20) were significantly associated with the age-standardized elective CS rate after adjusting for socioeconomic factors (R2 for the model = 0.40). CONCLUSIONS: Higher elective CS rates might be associated with limited or unconsolidated medical resources. Policymakers should be aware of regional differences and the possible effects of perinatal care resources on CS rates.