森 千里

In the modern society, people are exposed to various pollutants during their lifetime. Worldwide, the status of children's health has changed in recent decades. Some studies have attempted to identify the causes of these changes and whether they relate to pollutant exposure; however, such attempts have faced major challenges because human life is complex, involving many social and environmental factors. Several long-term cohort studies are being conducted to determine the relationship between diseases and social and environmental factors in children. Even before we establish complete proof of adverse effects, we should attempt to decrease risk to future generations by adopting precautionary principles. Environmental exposure to persistent organic pollutants can be reduced throughout the stages of life-the fetal period, newborn and infant periods, childhood, adolescence and adulthood (preconception) by individuals as well as by society as a whole. Through reducing environmental exposure to pollutants, adverse health effects can also be reduced, which will contribute to healthier future generations. Here, we suggest a virtuous cycle for improving the health of future generations through reduced exposure to persistent pollutants.

Several intrauterine environmental factors can increase the future risk of type 2 diabetes. The microbiome can influence the balance between health and disease. However, the influence of the maternal gut microbiome on the future risk of diabetes in the fetus is unknown. The present study investigated the associations between maternal gut microbiome and differentially methylated regions of diabetes-associated genes in umbilical cord samples. The present study included 10 pregnant participants from a birth cohort study. 16S ribosomal ribonucleic acid metagenome analysis of maternal stool samples and deoxyribonucleic acid methylation assays of umbilical cord samples were carried out. The present study found that changes in the UBE2E2 and KCNQ1 methylation rates in umbilical cord samples were associated with the proportion of Firmicutes in the maternal gut, albeit with marginal correlations after adjustment for age and body mass index. These findings suggest a link between the methylation of diabetes-associated genes in fetuses and maternal microbiota components during pregnancy.

There is worldwide concern about the effects of environmental factors on children's health and development. The Miami Declaration was signed at the G8 Environment Ministers Meeting in 1997 to promote children's environmental health research. The following ministerial meetings continued to emphasize the need to foster children's research. In response to such a worldwide movement, the Ministry of the Environment, Japan (MOE), launched a nationwide birth cohort study with 100,000 pairs of mothers and children, namely, the Japan Environment and Children's Study (JECS), in 2010. Other countries have also started or planned large-scale studies focusing on children's environmental health issues. The MOE initiated dialogue among those countries and groups to discuss and share the various processes, protocols, knowledge, and techniques for future harmonization and data pooling among such studies. The MOE formed the JECS International Liaison Committee in 2011, which plays a primary role in promoting the international collaboration between JECS and the other children's environmental health research projects and partnership with other countries. This review article aims to present activities that JECS has developed. As one of the committee's activities, a workshop and four international symposia were held between 2011 and 2015 in Japan. In these conferences, international researchers and government officials, including those from the World Health Organization, have made presentations on their own birth cohort studies and health policies. In 2015, the MOE hosted the International Advisory Board meeting and received constructive comments and recommendations from the board. JECS is a founding member of the Environment and Child Health International Birth Cohort Group, and has discussed harmonization of exposure and outcome measurements with member parties, which will make it possible to compare and further combine data from different studies, considering the diversity in the measurements of variables between the studies. JECS is expected to contribute to the international environmental health research community and policy-making. More international collaboration would enhance our understanding of the possible environmental causes of diseases and disabilities.

For a longitudinal prospective cohort study to be successful, participants' motivation to provide information must be maintained. Therefore, this study aimed to identify items that effectively promote participants' motivation. Questionnaires were mailed to 4541 mothers and expectant mothers in Chiba Prefecture, Japan who participated in a nationwide birth cohort. A total of 2387 (52.6%) responses were received. The following items were identified as primary motivating factors among our cohort: "benefits to the participants' children", "monetary compensation" and "contribution to a better future environment". More than 30% of the respondents expressed a lack of understanding regarding the study purpose and requirements for participation. About 14% were concerned about the leakage of personal information, and 13% felt burdened by having to make a long-term commitment to the study. Cluster analysis identified four groups, two of which, one with extremely low levels of motivation and the other motivated by only money or goods, lacked an understanding of the study and tended to be concerned about the associated risks and burdens. Participants in these groups were considered to be at a high risk of dropout. Therefore, implementing measures to provide participants with a better understanding of cohort studies could lead to more successful results.

<p>The toxicity of decabromodiphenyl ether (BDE-209) has been reported in several studies. However, there is not much known about the toxicological biomarkers that characterize BDE-209 exposure. In this study, we subcutaneously exposed mice to 0.025 mg/kg/day BDE-209 on postnatal days 1‑5 and sacrificed the animals at 12 weeks of age (day 84). Flow injection analysis and hydrophilic interaction chromatography-triple quadrupole mass spectrometry were used to determine the serum metabolomes of these mice in order to characterize the effects of BDE-209 exposure. Data analysis showed a good separation between control and exposed mice (R² = 0.953, Q² = 0.728, and ANOVA of the cross‑validated residuals (CV‑ANOVA): P‑value = 0.0317) and 54 metabolites were identified as altered in the exposed animals. These were selected using variable importance (VIP) and loadings scaled by a correlation coefficient criteria and orthogonal partial least squares discriminant analysis (OPLS‑DA). BDE‑209‑exposed mice showed lower levels of long-chain acylcarnitines and citrate cycle-related metabolites, and higher levels of some amino acids, long-chain phospholipids, and short-chain acylcarnitines. The disruption of fatty acid, carbohydrate, and amino acid metabolism observed in the serum metabolome might be related to the previously observed impaired spermatogenesis in mice with early postnatal exposure to a low dose of BDE-209.</p>

Carotid-cavernous sinus fistula (CCF) is a rare complication occurring after the Le Fort osteotomy. We aimed to elucidate the cause of CCF in the Le Fort osteotomy. Methods Eleven fresh cadavers were used. After craniotomy, a Le Fort III bipartition osteotomy was then performed. On the left side, both the lateral wall of the maxilla and the pterygomaxillary junction (PMJ) were divided, in addition to the conventional osteotomy line. On the right side, those parts were kept intact. After the osteotomy, a tensiometer was fixed to the skull base. The sensor was linked with the wall of the carotid artery in the cavernous portion. A down-fracture was then performed initially from the left, followed by the right. Tensile force data of both sides were recorded. Results In all cases, a higher tensile load was observed on the right side compared to the left side. In right side, two skull base fractures complexed with high pterygoid process fractures, and nine pure high fractures of the pterygoid process were identified. Conclusions During down-fracture, the wall of the carotid artery experiences significant tensile load. The tensile load on the arterial wall may collapse the fine branches of the carotid artery in the cavernous portion.

© 2015 Takehiro Michikawa et al. Background: The Japan Environment and Children's Study (JECS) is an ongoing nationwide birth cohort study launched in January 2011. In this progress report, we present data collected in the first year to summarize selected maternal and infant characteristics. Methods: In the 15 Regional Centers located throughout Japan, the expectant mothers were recruited in early pregnancy at obstetric facilities and/or at local government offices issuing pregnancy journals. Self-administered questionnaires were distributed to the women during their first trimester and then again during the second or third trimester to obtain information on demographic factors, physical and mental health, lifestyle, occupation, environmental exposure, dwelling conditions, and socioeconomic status. Information was obtained from medical records in the first trimester and after delivery on medical history, including gravidity and related complications, parity, maternal anthropometry, and infant physical examinations. Results: We collected data on a total of 9819 expectant mothers (mean age = 31.0 years) who gave birth during 2011. There were 9635 live births. The selected infant characteristics (singleton births, gestational age at birth, sex, birth weight) in the JECS population were similar to those in national survey data on the Japanese general population. Conclusions: Our final birth data will eventually be used to evaluate the national representativeness of the JECS population. We hope the JECS will provide valuable information on the impact of the environment in which our children live on their health and development.

Establishing methods for the assessment of fetal exposure to chemicals is important for the prevention or prediction of the child's future disease risk. In the present study, we aimed to determine the influence of molecular weight on the likelihood of chemical transfer from mother to fetus via the placenta. The correlation between molecular weight and placental transfer rates of congeners/isomers of polychlorinated biphenyls (PCBs) and dioxins was examined. Twenty-nine sample sets of maternal blood, umbilical cord, and umbilical cord blood were used to measure PCB concentration, and 41 sample sets were used to analyze dioxins. Placental transfer rates were calculated using the concentrations of PCBs, dioxins, and their congeners/isomers within these sample sets. Transfer rate correlated negatively with molecular weight for PCB congeners, normalized using wet and lipid weights. The transfer rates of PCB or dioxin congeners differed from those of total PCBs or dioxins. The transfer rate for dioxin congeners did not always correlate significantly with molecular weight, perhaps because of the small sample size or other factors. Further improvement of the analytical methods for dioxin congeners is required. The findings of the present study suggested that PCBs, dioxins, or their congeners with lower molecular weights are more likely to be transferred from mother to fetus via the placenta. Consideration of chemical molecular weight and transfer rate could therefore contribute to the assessment of fetal exposure. (C) 2014 Elsevier Ltd. All rights reserved.

Sick-building syndrome (SBS) is a range of symptoms such as eye irritation, sore throat, and headaches that occur when entering a newly constructed or refurbished building. Volatile organic compounds (VOCs) are suspected to be one of the major causes of SBS. However, although Ministry of Health, Labour, and Welfare of Japan set the guideline values for 13 VOCs, the incidences of SBS patients have not decreased. In addition, there have been reports that when people complained symptoms of SBS, most of them also claimed to smell an odour. Furthermore, the occurrence of SBS symptoms depends largely on the person's sensitivity. In this study, the correlation between the sum of VOCs(C2-C16) including aldehydes (sigma VOCs) and SBS symptoms were examined by statistics. The odour was quantified using the odour threshold ratio (OTR) and the correlation between the total odour threshold ratio (TOTR: sum of the OTR) and SBS symptoms was investigated. These correlations were examined separately for sensitive and insensitive groups. TOTR and the concentration level of sigma VOCs were correlated with SBS symptoms among sensitive people. The findings indicate that TOTR, in addition to sigma VOCs, could be used as a new risk indicator for human health regarding indoor air quality.

Diethylstilbestrol (DES), an endocrine-disrupting chemical, is an infamous artificial estrogenic compound. Although neonatal exposure to DES has been shown to result in inflammation of the male reproductive system, it has not, to our knowledge, been reported to induce testicular inflammation. Here we report that neonatal exposure to DES caused granulomatous orchitis with spermatogenic disturbance in 4 of 17 ICR male mice at 12 weeks of age. In the animals with spermatogenic disturbance, we observed either seminiferous tubules containing only cells with Sertoli cell features (likely Sertoli cell syndrome), or tubule cells in maturation arrest that contained only spermatogonia and/or spermatocytes. Following neonatal DES exposure, 5-week-old mice exhibited inflammation in cauda epididymis; by 8 weeks, the inflammation had spread to all segments of epididymis but not the testis; by 12 weeks, inflammation of the epididymis was observed in all mice. These data indicated that cauda epididymis has increased sensitivity to neonatal DES exposure compared to other segments of epididymis and testis. The data also implied that neonatal DES exposure-induced inflammation in cauda epididymis extended gradually to the testis via corpus and caput during development.

Individuals' exposure to various persistent organic pollutants (POPs), including polychlorinated biphenyls (PCBs), and its adverse health effects have been a cause of concern. We measured blood PCB concentrations from samples taken from 507 Japanese individuals ranging from infants to those over 80 years of age. The blood PCB levels increased with age for both male (Spearman's r = 0.69, p &lt; 0.001) and female (Spearman's r = 0.70, p &lt; 0.001) participants. Adult men and nulliparous women showed similar increases with age. However, the PCB levels of multiparous women were lower than those of nulliparous women in their thirties (p = 0.005), probably because the PCBs were transferred from the mothers to their children during pregnancy and lactation. Among infants (&lt;2 years of age), some had as high levels of accumulated PCB levels as those in adults &gt;30 years of age. In some cases, the PCB levels were over 0.8 ng/g wet weight, similar to levels observed in adults over 50 years of age. In the future, it will be necessary to do research on the health of the children who are exposed by high concentration level of POPs.

Chiba University has participated the international solar housing competition called Solar Decathlon Europe 2012. This paper reports the design process and construction result of the proposal called Omotenashi House. Chiba University has been designing a net-zero-energy and food self-sufficient model since 2011 including insulation system, landscape, structural planning, PV system, natural and artificial lightings, and active and passive systems. Finally Omotenashi House has been exported to and reassembled in Spain in 12 days, and measured its high energy efficiency and electrical balance with low VOC emissions.

The indoor air concentrations of chemicals play an important role in the quality of air at indoor locations. Accordingly, chemicals-volatile organic compounds (VOCs) and aldehydes-at six experimental sites were measured and analyzed, and the results were compared with those of a similar study conducted two years ago. In contrast to the previous study, which reported a decline in the concentrations of VOCs over a five-year observation period, the comparison showed an increase in the concentrations. Furthermore, aldehydes with relatively low odour thresholds were found to have increased, which may explain the strong odour reported by volunteers in a test that was conducted to evaluate the quality of indoor air through human sensory perception. And it was also marked by the appearance of sesquiterpenes. Thus, these results indicate that it is necessary to recognize that the decline in indoor air concentrations of VOCs may be reversed over time. (up to 150 words).

Increasing evidence supports that harmful chemicals accumulating in the human body may pose a significant threat to infant health through foetal exposure. Persistent organic pollutants (POPs) are thought to enhance the risk for later development of allergic disease like atopic dermatitis (AD). However, few studies have evaluated the effect of foetal exposure to various POPs on the development of AD in early infancy. Here, we describe the impact of foetal exposure to a number of POPs on the occurrence of AD in 7-month-old infants. The participants were 81 infants with or without AD who participated in a birth cohort study, where the concentrations of 15 polychlorinated biphenyl (PCBs) congeners, dichlorodiphenyltrichloroethane (p,p'-DDT), dichlorodiphenyldichloroethylene (p,p'-DDE), beta-hexachlorocyclohexane (beta-HCH), hexachlorobenzene (HCB), cis-nonachlor, trans-nonachlor, mirex, oxychlordane, and 27 polybrominated diphenyl ether (PBDEs) congeners were measured in the umbilical cord tissues collected immediately after birth. At 7 months, 27 of the 81 infants (33.8%) were diagnosed with AD. Of all POPs examined, total concentrations of 27 PBDE congeners were associated with a significantly decreased incidence of AD. Notably, the concentration of 27 PBDEs was significantly lower in AD infants than in non-AD infants (P &lt; 0.01), and the risk of AD development decreased with increasing PBDE levels. These results suggest that foetal exposure to PBDEs is a possible contributing factor to reducing AD in early infancy. (C) 2013 Elsevier Ltd. All rights reserved.

Decabromodiphenyl ether (decaBDE) adversely affects reproduction and development. Our previous study showed that postnatal exposure to a low dose of decaBDE (0.025 mg/kg body weight/day) by subcutaneous injection on postnatal days (PNDs) 1 through 5 leads to reductions in testicular size and number of Sertoli cells and sperm, while higher dose of decaBDE (2.5 mg/kg body weight/day) had no significant differences about these. In the present study, we examined the molecular mechanism of these effects on mouse testes following postnatal exposure to a low decaBDE dose. We hypothesized that postnatal exposure to decaBDE may alter levels of serum thyroid hormones (THs) and testosterone, or the level of TH receptor alpha (Thra) transcripts and its splicing variants and androgen receptor (Ar) in Sertoli cells, adversely affecting spermatogenesis. To test this hypothesis, we examined serum TH and testosterone levels and the levels of transcripts of the Ar, Thra and its splicing variants, and Thra splicing factors (Hnrnpa1, Srsf1, and Hnrnph1) with qPCR in isolated mouse Sertoli cells exposed postnatally to decaBDE (0.025, 0.25, and 2.5 mg/kg). Levels of serum testosterone and transcripts encoding Ar, Thra, and its variant, Thra1, declined significantly in Sertoli cells of mice exposed to 0.025 mg decaBDE/kg. No significant differences in serum TH level or Thra2, Hnrnph1, or Srsf1 transcript levels were observed between control and decaBDE-exposed mice. However, the Thra1:Thra2 and Hnrnpa1:Srsf1 ratios were altered in Sertoli cells of mice exposed to 0.025 mg decaBDE/kg but not in cells exposed to 0.25 or 2.5 mg decaBDE/kg. These results indicate that postnatal exposure to a low dose of decaBDE on PNDs 1 through 5 lowers the testosterone level and the levels of Ar and Thra transcripts in Sertoli cells, accompanied by an imbalance in the ratios of Thra splicing variants, resulting in smaller testicular size and impaired spermatogenesis.

Exposure to di-(2-ethylhexyl) phthalate (DEHP) has been reported to induce spermatogenic disturbance through oxidant stress and affect the immune system as an adjuvant. However, the effect of DEHP on the testicular immune microenvironment has not yet been investigated. In the present study, we examined the testicular immune microenvironment after exposure to doses of DEHP, previously identified as no-observed-adverse-effect levels. Adult male mice were administered food containing 0%, 0.01% or 0.1% DEHP and then testes were analyzed. The results showed that a slight but significant spermatogenic disturbance appeared in the 0.1% DEHP group but not in the 0.01% DEHP group at 8 weeks. It was also demonstrated that lymphocytes and F4/80- and MHC class II- positive cells were significantly increased with the elevation of IL-10 and IFN-γ mRNA expressions in the testes of not only the 0.1% DEHP group but also the 0.01% DEHP group at 8 weeks. Histochemical analyses involving horseradish peroxidase (HRP) as a tracer showed that a little blood-borne HRP had infiltrated into the lumen of a few seminiferous tubules beyond the blood-testis-barrier in both the 0.1% and 0.01% DEHP groups at 8 weeks. This indicates that a dose of DEHP that has little effects on spermatogenesis can change the testicular immune microenvironment with functional damage of the blood-testis barrier.

The purpose of this study was to develop a prediction tool for designing and building houses with low volatile organic compounds(VOCs) to prevent people diagnose sick building syndrome. First, 116 VOCs were analyzed in detail from 124 indoor air samples collected at 29 rooms in 8 houses for over 5 years. Next, multivariate analysis was conducted to find the influencing factors and con-tribution on the VOC emission. As the results, it became clear that flooring materials, construction method and time after finishing construction were the major factors. Finally, a prediction tool of VOC level in indoor air was designed.

Background: Few reports describe devastating complications with conventional Le Fort III osteotomy; however, life-threatening complications have been reported occasionally with Le Fort III distraction. An anatomical study using cadaveric Le Fort III osteotomy models was performed to investigate the causes of untoward fractures that might induce devastating complications. Methods: The study sample consisted of 30 cadavers (60 sides). Specimens were separated into six groups depending on whether osteotomy of the lateral maxillary wall from the inferior orbital fissure to the pterygomaxillary junction (procedure A) and separation of the pterygomaxillary junction (procedure B) were performed completely, incompletely, or not at all. All osteotomy and fracture lines including the skull base and orbit were examined by computed tomography and direct observation. The separation or fracture type of the pterygoid plate of the sphenoid bone was categorized into four groups: ideal separation, low-level fracture, high-level fracture, and others. The frequency of each type of pterygoid plate fracture between controls and each group was compared. Results: High-level fractures occurred more frequently in groups with intact pterygomaxillary junctions. All specimens with untoward fractures of the sphenoid bone leading to the skull base or carotid canal accompanied high-level pterygoid fractures, occurring in groups without sufficient pterygomaxillary separation. An extraordinary orbital fracture was observed when neither procedure A nor procedure B was performed. Conclusions: Precise separation of the pterygomaxillary junction is primarily of importance for preventing devastating complications of Le Fort III osteotomy and Le Fort III distraction. Osteotomy of the lateral maxillary wall is also necessary to minimize this risk. (Plast. Reconstr. Surg. 131: 19e, 2013.)

Azole derivatives have teratogenic effects in rodents. In the present study, malformations and their sensitive windows induced by high-dose ketoconazole (KCZ), an azole derivative, without maternal toxicity were investigated. In addition, the malformation spectrum determined was compared with that induced by vitamin A palmitate (VAP). Pregnant rats were administered a single dose of KCZ by oral gavage on specific individual days from gestational days 8 to 15 (GDs 8-15). Maternal animals were subjected to necropsy on GD 20, and the obtained fetuses were examined for external, visceral and skeletal malformations. The malformation spectrum of VAP was identified from available published data (Noda, Sato, and Udaka, 1982) and a complementary study (single administration of VAP at 1 200 000IU kg -1). Embryonic lethality was observed in dams given KCZ on GDs 9-12 with peak incidence on GDs 10 and 11 with complete resorption. KCZ induced major malformations included cleft palate, digital anomalies, misshapen limbs and unique discontinuous ribs, and the sensitive window for each was identified. Compared with the malformations induced by VAP, unique malformations (e.g. discontinuous ribs by KCZ, neural tube defects by VAP), similar malformations with similar sensitive windows (e.g. digital and limb malformations) and similar malformations with different sensitive windows (e.g. embryonic lethality and cleft palate) were distinguished, suggesting that the mechanisms of several of the types of KCZ-induced malformation are related to excessive vitamin A. © 2011 John Wiley &amp Sons, Ltd.

Background: Environmental exposure to formaldehyde is commonly associated with clinical symptoms such as mucosal irritation and olfactory disorders. However, the impact of such exposure on the development of mucosal inflammation and its outcome has not been carefully evaluated. Methods: The observational non-comparative study was planned. The study population consisted of group of 41 medical students who had signed up for a cadaver dissection course as part of their gross anatomy teaching at the school of medicine Chiba University in Japan. During such dissection course, the students are exposed to variable levels of environmental formaldehyde routinely employed for the preservation the cadavers. The subjects were evaluated by a detailed medical examination. We measured their serum IgE levels. In addition, an olfaction test and nasal mucosal sensitivity to histamine was serially determined, immediately before and after the course and 6 months after the completion of the course. Results: Olfactory abnormalities were observed in 13/41 (32%) subjects and increased nasal mucosal hypersensitivity to histamine was observed in 17/41 (41%) during and immediately after completion of the course. These subjects had evidence of preexisting allergic rhinitis. 6/41 (15%) other students with no prior evidence of allergic rhinitis also exhibited formaldehyde associated clinical symptoms during the dissecting course. However, the symptoms disappeared upon completion of the course in all subjects studied. Conclusions: Temporary abnormalities in the olfaction test and increased nasal mucosal hypersensitivity to histamine were observed in a few students with preexisting allergic rhinitis after environmental exposure of high concentrations of formaldehyde. These effects appeared to be transient. © 2011 Japanese Society of Allergology.

We measured the concentration of each polychlorinated biphenyl (PCB) congener in whole blood, plasma and blood cells, and investigated the distribution of PCBs in human blood using high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS). The PCB concentrations in plasma and whole blood in terms of lipid concentrations were almost equal, with a correlation coefficient of r = 0.972. In the blood, the ratio of PCBs in blood cells to those in plasma was generally about 1:9 and the congener distribution patterns in blood cells and plasma were similar. We performed verification of a simple mass screening method by obtaining information on the main PCB congeners for investigations on human accumulation and exposure. The total concentration of the seven PCB congeners (UNEP-7) proposed to the United Nations Environment Programme (UNEP) by Muir and Morita was about 50% of the total concentration of all PCB congeners, and UNEP-30 was about 80%. The seven main congeners in the blood (MCB-7) showed a value that was about 60%, and MCB-30 showed a value that was about 90%. Determinations with the main congeners in the blood showed a correlation of r = 0.990 or more between the main eight congeners (MCB-7 plus #74) and the total PCB concentration for all congeners. The results suggest that, although total PCB concentration can be effectively estimated from the main seven congeners, the main eight congeners would be preferable, and that the use of these congeners in the simple mass screening method would be effective for populations in areas uncontaminated by PCBs. (C) 2010 Elsevier Ltd. All rights reserved.