Progress report of the Tohoku Medical Megabank Community-Based Cohort Study: Study profile of the repeated center-based survey during second period in Miyagi Prefecture.

BACKGROUND: The purpose of this study was to report the basic profile of the Miyagi Prefecture part of a repeated center-based survey during the second period (2nd period survey) of the Tohoku Medical Megabank Community-Based Cohort Study (TMM CommCohort Study), as well as the participants' characteristics based on their participation type in the baseline survey. METHODS: The 2nd period survey, conducted from June 2017 to March 2021, included participants of the TMM CommCohort Study (May 2013 to March 2016). In addition to the questionnaire, blood, urine, and physiological function tests were performed during the 2nd period survey. There were three main ways of participation in the baseline survey: Type 1, Type 1 additional, or Type 2 survey. The 2nd period survey was conducted in the same manner as the Type 2 survey, which was based on the community support center (CSC). RESULTS: In Miyagi Prefecture, 29,383 (57.7%) of 50,967 participants participated in the 2nd period survey. The participation rate among individuals who had visited the CSC was approximately 80%. Although some factors differed depending on the participation type in the baseline survey, the 2nd period survey respondents in the Type 1 and Type 2 survey groups at baseline had similar traits. CONCLUSIONS: The 2nd period survey of the TMM CommCohort Study provided detailed follow-up information. Following up on the health conditions of the participants will clarify the long-term effects of disasters and contribute to personalized prevention.

Detection and Correction of Sample Misidentifications in a Biobank Using the MassARRAY System and Genomic Information.

With the number of samples increasing in many biobanks, one of the most pressing tasks is recording the correct relationships between information and the specimens. Genomic information is useful in determining the identity of these specimens. The Tohoku Medical Megabank Organization is running one of the largest biobanks in Japan. Here, we introduce a management system, which includes the development of a new probe set for the MassARRAY system for use during the production of proliferating T cells (T cells) and lymphoblastoid cell lines (LCLs). We selected single nucleotide variants that could be detected by next-generation sequencing and showed high resolution with ∼0.5 minor allele frequencies. After checking the set of probes against 96 samples from 48 people, we obtained no contradictory results in comparison with our genome sequence information. When we applied the set to our 3035 LCLs and 2256 T cells, the result showed 98.93% consistency with the corresponding genomic information. We surveyed the handling records of the 1.07% of samples that showed inconsistencies, and found that most had resulted from human errors (ID swapping between samples) during manual operations. After improving a few error-prone protocols, the error rate dropped to 0.47% for LCLs and 0% for T cells. Overall, the system that we developed shows high accuracy with easy and fast operability, and provides a good opportunity to improve the validation procedure to facilitate high-quality banking, especially in cases involving genomic information.

Secretin receptor-deficient mice exhibit robust food anticipatory activity.

In mammals, the suprachiasmatic nucleus (SCN) is a principal circadian pacemaker that optimizes the timing of behavioral rhythms and physiological events. Normally, circadian behavioral rhythms are entrained by the environmental light-dark (LD) cycle via the SCN. However, daily rhythms of other synchronizing signals, such as food availability, also emerge. When food availability is restricted to a single recurring daytime meal in nocturnal rodents, they exhibit increased activity during the hours immediately preceding feeding time; this is called food anticipatory activity (FAA). Many reports suggest that FAA is mediated by the food-entrainable oscillator (FEO) with circadian properties, but not the SCN. However, the neural locus and timekeeping mechanisms of the FEO, including its relationship with gastrointestinal hormone signaling, remain unclear. Herein, to examine whether secretin receptor signaling is necessary for the FEO, the effect of daily food restriction was studied in secretin receptor-deficient (Sctr-/-) mice. Adult wild-type (WT) and Sctr-/- mice were housed in separate cages containing a running wheel, with ad libitum food access and in a LD cycle (12 hours:12 hours) for at least 2 weeks. After acclimation to the condition, food access times were gradually restricted and 4-hour restricted feeding lasted over 10 days. Subsequently, mice had ad libitum food access for 2 days and then fasted for 2 days. Thereafter, robust FAAs were observed in both WT and Sctr-/- mice during restricted feeding and subsequent fasting. These results indicate that secretin receptor signaling is not essential for the timekeeping mechanism of FEO.

Landscape of electrophilic and inflammatory stress-mediated gene regulation in human lymphoblastoid cell lines.

Human lymphoblastoid cell lines (LCLs) are valuable for the functional analyses of diseases. We have established more than 4200 LCLs as one of the resources of an integrated biobank. While oxidative and inflammatory stresses play critical roles in the onset and progression of various diseases, the responsiveness of LCLs, especially that of biobank-made LCLs, to these stresses has not been established. To address how LCLs respond to these stresses, in this study, we performed RNA sequencing of eleven human LCLs that were treated with an electrophile, diethyl maleate (DEM) and/or an inflammatory mediator, lipopolysaccharide (LPS). We found that over two thousand genes, including those regulated by a master regulator of the electrophilic/oxidative stress response, NRF2, were upregulated in LCLs treated with DEM, while approximately three hundred genes, including inflammation-related genes, were upregulated in LPS-treated LCLs. Of the LPS-induced genes, a subset of proinflammatory genes was repressed by DEM, supporting the notion that DEM suppresses the expression of proinflammatory genes through NRF2 activation. Conversely, a part of DEM-induced gene was repressed by LPS, suggesting reciprocal interference between electrophilic and inflammatory stress-mediated pathways. These data clearly demonstrate that LCLs maintain, by and large, responsive pathways against oxidative and inflammatory stresses and further endorse the usefulness of the LCL supply from the biobank.

Secretin receptor-deficient mice exhibit altered circadian rhythm in wheel-running activity.

In mammals, the timing of behavior and physiological activity is controlled by the suprachiasmatic nucleus (SCN) in the hypothalamus. Incidentally, secretin is a peptide hormone that promotes digestive activities and regulates water reabsorption. In recent studies, exogenous administration of secretin has been reported to induce secretion of oxytocin in the supraoptic nucleus of the hypothalamus and modulate social behavior. These results indicate that secretin is involved in the neural network that controls social behavior and plays important roles in the central nervous system. In the present study, we investigated the effects of secretin on circadian rhythms, by assessing circadian rhythms during wheel-running behavior in secretin receptor-deficient (Sctr-/-) mice. Male adult wild-type (WT) and Sctr-/- mice were housed in separate cages containing a wheel. Every minute of the wheel-running activity was monitored during the normal light-dark (LD) cycle (12:12 h) and in constant darkness (DD). Significant differences were observed in the free-running period between the WT and Sctr-/- mice. However, no significant differences were observed in the daily wheel-running revolutions between WT and Sctr-/- mice, in the LD and DD conditions. Moreover, the ratio of the daily activity phase to the rest phase (α/ρ) was significantly smaller in Sctr-/- than that in WT mice in the DD condition. Secretin receptors were expressed in the SCN cells. These findings suggest that secretin receptors are involved in the central circadian clock in the SCN and the circadian system in general.

Update on the prevalence and determinants of folic acid use in Japan evaluated with 91,538 pregnant women: the Japan Environment and Children's Study.

Objective: To provide the latest and most promising evidence on the prevalence and determinants for folic acid supplementation in pregnant women in Japan, including differences in prevalence between interview years and determinants across regions.Materials and methods: The study participants were enrolled from 15 regional centers across Japan between January 2011 and March 2014. Information on the use of folic acid supplementation before and during pregnancy and the characteristics of the participants were collected using questionnaires, medical chart reviews, and interviews by research coordinators.Results: Data for 91,538 women who provided sufficient data on folic acid supplementation were analyzed. The prevalence of adequate users was 8.0%, which, although low, tended to improve over the 4-year recruitment period. Various kinds of sociodemographic factors, lifestyle habits, and obstetrical and medication use history were significant and independent determinants for folic acid use. Associations between adequate preconception folic acid use and its major determinants tended to be similar across regions.Conclusions: Although the prevalence of adequate folic acid use was low, it increased from 2011 to 2014. Reproductive-aged women who have determinants for inadequate folic acid use should be informed about the need for preconception folic acid supplementation to help prevent neural tube defects.

Biobank Establishment and Sample Management in the Tohoku Medical Megabank Project.

The Tohoku Medical Megabank biobank (TMM biobank) is the first major population-based biobank established in Japan. The TMM biobank was established based on two population cohorts and is a reconstruction program from the Great East Japan Earthquake and Tsunami of 2011. The biobank stores more than 3.4 million tubes of biospecimens and associated health and analytic data obtained from approximately 150,000 TMM cohort participants between May 2013 and December 2018, and the TMM biobank currently shares high-quality specimens and data. Various biospecimens, including peripheral and cord blood mononuclear cells, buffy coat, plasma, serum, urine, breast milk and saliva have been collected in the TMM biobank. To minimize human error and maintain the quality of data and specimens, we have been utilizing laboratory information management system into various biobank procedures from registration to storage with various automation systems, such as liquid dispensing, DNA extraction and their storage. The biobank procedures for the quality management system (ISO 9001:2015) and information security management system (ISO 27001:2013) are certified by the International Organization for Standardization. The quality of our biobank samples fulfills the pre-analytical requirements for researchers conducting next-generation whole genome sequencing, DNA array analyses, proteomics, metabolomics, etc. We established analytical centers to conduct standard genomic and multiomic analyses in-house and share the generated data. Additionally, we generate thousands of Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines and proliferating T cells for functional studies. The TMM biobank serves as an indispensable infrastructure for academic, clinical and industrial research to actualize next-generation medicine in Japan.

The risk of secondary sex ratio imbalance and increased monozygotic twinning after blastocyst transfer: data from the Japan Environment and Children's Study.

BACKGROUND: Some studies have suggested that blastocyst transfer is associated with i) imbalance in the secondary sex ratio (SSR) (which favors male offspring), ii) increased incidence of monozygotic twins (MZT). In contrast, others have not found these changes. In this study, we evaluated the association between blastocyst transfer and SSR and MZT, considering potential parental confounders. METHODS: The Japan Environment and Children's Study is a large, nationwide longitudinal birth cohort study funded by the Ministry of the Environment of Japan. We used this large dataset, including 103,099 pregnancies, to further investigate the association between blastocyst transfer, SSR and MZT, using spontaneously conceived pregnancies, non-assisted reproductive technology (non-ART) treatment (intrauterine insemination and ovulation induction with timed intercourse) and cleavage stage embryo transfer for comparison. We evaluated the association with each group, the SSR, and the frequency of MZT, calculating the adjusted odds ratio (AOR) using multivariable logistic regression analyses, adjusting for potential parental confounders such as basic health and socioeconomic status. RESULTS: For each group (spontaneous conception vs. non-ART treatment vs. cleavage stage embryo transfer vs. blastocyst transfer), the percentages of males were 51.3% vs 50.7% vs 48.9% vs 53.4% and the monozygotic twinning rates per pregnancy were 0.27% vs 0.11% vs 0.27% vs 0.99% respectively. Multivariate logistic regression analyses indicated that blastocyst transfer was significantly associated with a higher SSR and higher incidence of MZT than the other three groups (SSR: AOR 1.095, 95% CI1.001-1.198; MZT: AOR 4.229, 95% CI 2.614-6.684). CONCLUSIONS: There are significant relationships between blastocyst transfer and SSR imbalance and a higher occurrence of MZT.

Blood pressure changes during twin pregnancies: the Japan Environment and Children's Study.

OBJECTIVES: Although a twin pregnancy is a risk factor for hypertensive disorders of pregnancy, studies investigating longitudinal blood pressure changes during twin pregnancies are uncommon. The aims of this study were to evaluate the longitudinal blood pressure changes during twin pregnancies and to compare blood pressure levels between twin and singleton pregnancies. METHODS: Five hundred dichorionic diamniotic twin, 240 monochorionic diamniotic twin, and 80 775 singleton pregnancies were included in this Japanese prospective birth cohort study. A marginal model was applied to evaluate the SBP, DBP, and mean arterial pressure levels during early gestation, mid-gestation, and late gestation. RESULTS: The blood pressure levels fell from early-to-mid-gestation and rose after mid-gestation in the dichorionic and monochorionic diamniotic twin pregnancies. The SBP and mean arterial pressure levels during early gestation and the DBP and mean arterial pressure levels during late gestation were higher in the dichorionic diamniotic twin pregnancies than those in the singleton pregnancies. The blood pressure levels in the monochorionic diamniotic twin pregnancies were higher than those in the singleton pregnancies at each gestational stage, except for the SBP during late gestation. CONCLUSION: Although the longitudinal blood pressure changes during twin pregnancies were similar to those during singleton pregnancies, the blood pressure levels during twin pregnancies were higher. Further studies that examine the associations between the longitudinal blood pressure changes during pregnancy and the perinatal outcomes in twin pregnancies are necessary.

Association between alcohol consumption during pregnancy and hypertensive disorders of pregnancy in Japan: the Japan Environment and Children's Study.

This study examined the association between maternal alcohol consumption during pregnancy and hypertensive disorders of pregnancy in the Japan Environment and Children's Study, a nationwide birth cohort study. A total of 76 940 pregnant women were included in the analysis. Information about alcohol consumption during pregnancy was obtained using two questionnaires: T1 and T2. The mean (standard deviation) gestational age in the T1 and T2 questionnaires were 16.5 (5.8) and 27.9 (3.7) weeks, respectively. Alcohol consumption was considered as an exposure, hypertensive disorders of pregnancy as an outcome, and possible confounding factors were included in a generalized linear mixed-effects model with a logit link function. Among the study subjects, 2 348 (3.1%) women developed hypertensive disorders of pregnancy. Compared with 25 300 women who never drank alcohol, 43 women who drank alcohol according to the T1 questionnaire and continued to drink ≥150 g ethanol/week according to the T2 questionnaire had significantly higher odds of hypertensive disorders of pregnancy. The adjusted odds ratio was 3.98 (95% confidence interval [CI], 1.33-11.9). In conclusion, alcohol consumption of ≥150 g ethanol/week during pregnancy is better avoided because of the high odds of developing hypertensive disorders of pregnancy. It may be meaningful that healthcare providers confirm information about alcohol consumption during pregnancy. Moreover, discontinuation of alcohol consumption is recommended to prevent the onset of hypertensive disorders of pregnancy in Japan.

Drug Use before and during Pregnancy in Japan: The Japan Environment and Children's Study.

Purpose: To elucidate drug use before and during pregnancy in Japan. Methods: The Japan Environment and Children's Study (JECS) is an ongoing nationwide birth cohort study. We analyzed data from JECS involving cases where drugs were used for 12 months before pregnancy was diagnosed, between the time of diagnosis of pregnancy until week 12 of pregnancy, and after week 12 of pregnancy. Results: We analyzed data from 97,464 pregnant women. The percentages of pregnant women who had taken one or more drugs and supplements before diagnosis of pregnancy, between the time of diagnosis of pregnancy until week 12 of pregnancy, and after week 12 of pregnancy, were 78.4%, 57.1%, and 68.8% respectively. Excluding iron supplements, folic acid, and other vitamins and minerals, the percentages of women taking supplements were 75.3%, 36.0%, and 51.7% at each respective time point. The following drugs and supplements were frequently used for 12 months before pregnancy diagnosis: Commercially available antipyretics, analgesics, and/or medicine for treating common cold (34.7%), antipyretics, analgesics, and/or medicine for treating common colds, which were prescribed in hospitals (29.8%), antimicrobial drugs (14.0%), and anti-allergy drugs (12.5%). The following drugs and supplements were frequently used from the time of pregnancy diagnosis until week 12 of pregnancy, and after week 12 of pregnancy: folic acid (28.9% and 26.2%), antipyretics, analgesics and/or medicines for treating common cold, that were prescribed in hospitals (7.8% and 13.3%), Chinese herbal medicines (6.0% and 9.4%, and uterine relaxants (5.1% and 15.2%). Conclusions: The analysis of a nationwide cohort study showed that a high percentage of Japanese pregnant women were taking medicinal drugs. Further research is required to elucidate the relationship between drug use during pregnancy and birth defects in Japan.

Pregnant Women's Awareness of Social Capital in the Great East Japan Earthquake-Affected Areas of Miyagi Prefecture: The Japan Environment and Children's Study.

OBJECTIVE: We aimed to clarify the correlation between the 2011 Great East Japan Earthquake and pregnant women's awareness of social capital 3 to 9 months after the tsunami disaster. METHODS: We analyzed data on responses to a questionnaire by 7451 pregnant women in their second to third trimesters. The proportions of social capital-related items were calculated in the north and south coastal areas of Miyagi Prefecture and were compared with national samples. The factors associated with social capital were estimated by use of multivariate logistic regression analyses. RESULTS: The proportion of women feeling that they had helpful neighbors was higher (69.0% vs 56.7%, P=0.0005), the proportion of women regarding their communities as safe and secure was lower (51.7% vs 62.4%, P=0.002), and the proportion of women feeling that most people were trustworthy was lower (23.7% vs 32.9%, P=0.006) in the north coastal area than nationwide. Such differences were not observed in the less severely affected south coastal area. Age of 35 years or older, extended family, college or university graduation, and being multiparous were associated with the feeling of having helpful neighbors. CONCLUSION: The current status of pregnant women's awareness of social capital in disaster-affected areas was revealed. Continuous monitoring and support may be necessary to address this issue.(Disaster Med Public Health Preparedness. 2017;11:355-364).

Activation of Supraoptic Oxytocin Neurons by Secretin Facilitates Social Recognition.

BACKGROUND: Social recognition underlies social behavior in animals, and patients with psychiatric disorders associated with social deficits show abnormalities in social recognition. Oxytocin is implicated in social behavior and has received attention as an effective treatment for sociobehavioral deficits. Secretin receptor-deficient mice show deficits in social behavior. The relationship between oxytocin and secretin concerning social behavior remains to be determined. METHODS: Expression of c-Fos in oxytocin neurons and release of oxytocin from their dendrites after secretin application were investigated. Social recognition was examined after intracerebroventricular or local injection of secretin, oxytocin, or an oxytocin receptor antagonist in rats, oxytocin receptor-deficient mice, and secretin receptor-deficient mice. Electron and light microscopic immunohistochemical analysis was also performed to determine whether oxytocin neurons extend their dendrites into the medial amygdala. RESULTS: Supraoptic oxytocin neurons expressed the secretin receptor. Secretin activated supraoptic oxytocin neurons and facilitated oxytocin release from dendrites. Secretin increased acquisition of social recognition in an oxytocin receptor-dependent manner. Local application of secretin into the supraoptic nucleus facilitated social recognition, and this facilitation was blocked by an oxytocin receptor antagonist injected into, but not outside of, the medial amygdala. In the medial amygdala, dendrite-like thick oxytocin processes were found to extend from the supraoptic nucleus. Furthermore, oxytocin treatment restored deficits of social recognition in secretin receptor-deficient mice. CONCLUSIONS: The results of our study demonstrate that secretin-induced dendritic oxytocin release from supraoptic neurons enhances social recognition. The newly defined secretin-oxytocin system may lead to a possible treatment for social deficits.

Selective serotonin reuptake inhibitors and risk of major congenital anomalies for pregnancies in Japan: A nationwide birth cohort study of the Japan Environment and Children's Study.

We analyzed data from the Japan Environment and Children's Study (JECS), on the association between selective serotonin reuptake inhibitors (SSRI) use during pregnancy and the risk of developing of major congenital anomalies in Japan. JECS is an ongoing nationwide birth cohort study. The study includes 95 994 single pregnant women and their offspring. Among them, 172 used any SSRI up to the 12th gestational week. Crude analyses show a significantly increased incidence of upper limb, abdominal, and urogenital abnormalities. In particular, the incidence of microcephaly, hydrencephalus, esophageal atresia, small intestinal atresia, and achondroplasia was significantly higher with than without exposure to these substances. On multivariate analyses, urogenital abnormality was significant (odds ratio 3.227; 95% confidence interval: 1.460-7.134). This Japanese nationwide birth cohort survey clarified that the use of any SSRI until the 12th gestational week was associated with urogenital abnormality in children. The survey for association with minor classification abnormality needs further examination in Japan.

Prevalence and determinants of inadequate use of folic acid supplementation in Japanese pregnant women: the Japan Environment and Children's Study (JECS).

OBJECTIVE: The aim of the study was to clarify the prevalence and determinants of inadequate use of folic acid supplementation in pregnant Japanese women. METHODS: This study was part of the Japan Environment and Children's Study, a nationwide and government-funded birth cohort study. We collected information on the use of folic acid supplementation before and during pregnancy and characteristics of participants using self-administered questionnaire. RESULTS: Among 9849 women who completed the data collection for this study, the prevalence of inadequate users was 92.6% of the total population and varied from 84.5% to 96.2% among regions. On the basis of multivariate logistic regression analysis, younger age, not married, lower family income, multipara, natural conception and no history of spontaneous abortion were found to be determinants for inadequate users of folic acid supplementation. CONCLUSION: Most Japanese pregnant women show inadequate folic acid supplementation use. Japanese women of child-bearing age need to be specifically informed about the need for periconceptional intake of folic acid to prevent neural tube defects.

Incidence of Domestic Violence Against Pregnant Females After the Great East Japan Earthquake in Miyagi Prefecture: The Japan Environment and Children's Study.

OBJECTIVE: This study aimed to clarify the correlation between the 2011 Great East Japan Earthquake and domestic violence (DV) against pregnant females after the disaster in Miyagi Prefecture, an area damaged by the earthquake and tsunami. METHODS: We analyzed 7600 pregnant females from June to December 2011. The incidence of physical and mental DV and the proportions in the inland, north coastal, and south coastal areas of Miyagi Prefecture and nationwide were calculated, and a chi-square test was conducted for comparison. The risk factors for DV were estimated with multivariate logistic regression analyses on a prefecture-wide basis. RESULTS: The incidence levels for physical DV were found to be 5.9% in the north coastal area, which was significantly higher than in the inland area (1.3%, P=0.0007) and nationwide (1.5%, P<0.0001). There were no significant differences in the incidence of mental DV between the 3 areas in Miyagi Prefecture (inland 15.2%, north coast 15.7%, and south coast 18.8%) or nationwide (13.8%). Experiencing disease or injury in someone close and changes in the family structure were significantly associated with mental DV in Miyagi Prefecture. CONCLUSION: Continuous monitoring and support for pregnant females may be necessary to address this issue in disaster-affected areas. (Disaster Med Public Health Preparedness. 2017;11:216-226).

Fermented Food Consumption and Psychological Distress in Pregnant Women: A Nationwide Birth Cohort Study of the Japan Environment and Children's Study.

Health benefits of fermented foods are attracting attention worldwide, and they have been traditionally eaten in Japan. Moreover, a recent study showed the association between the higher intake of yogurt and lower prevalence of depressive symptoms during pregnancy. Psychological problems, such as anxiety and depression, during pregnancy are serious health concerns and may increase the risk of adverse outcomes in children. In this study, we explored the association between fermented food consumption and psychological distress in 10,129 pregnant Japanese women, using the fixed data of the Japan Environment and Children's Study (JECS), an ongoing nation-wide birth cohort study. Food consumption was assessed with a semi-quantitative food frequency questionnaire (FFQ), and the Kessler 6-item psychological distress scale (K6) was administered to eligible women during their second or third trimester to eliminate overlap with the period of hyperemesis gravidarum. The mean median gestation in the subjects was 24.8 weeks. In total, 9,030 subjects completed the K6 questionnaire and FFQ. Importantly, the prevalence of the K6 score of ≥ 13 was 3.1% (280 subjects). This value was lower compared to precedent studies, which may reflect that cooperative and health conscious subject participated in the survey. The multivariate logistic regression analysis indicates that the intake of yogurt, lactic acid beverages, cheese, Japanese pickles, miso soup, or fermented soybeans was not significantly associated with a K6 score of ≥ 13. In conclusion, the present cohort study shows no association between fermented food consumption and psychological distress symptoms during the second or third trimester of pregnancy.

Association between social capital and the prevalence of gestational diabetes mellitus: An interim report of the Japan Environment and Children's Study.

BACKGROUND: Social capital is generally defined as the quality and frequency of social interactions with relatives, neighbors, and society. Social capital refers to broad concepts of social interactions and structures in individuals, communities and societies such as trust (e.g., neighborhood trust, which is social cohesion with neighbors) and social support (e.g., emotional support, which is the level of the feeling of being loved). Studies during the last few decades have shown that there is a significant inverse association between social capital and the prevalences of diseases such as depression and acute coronary syndrome. Significant inverse associations between trust, social support and the prevalence of diabetes have also been shown. However, associations between social capital and the prevalence of gestational diabetes mellitus (GDM) are less clear. METHODS: We used the primary dataset of the Japan Environment and Children's Study (JECS), including 10,228 mothers with recorded obstetric outcomes from January to December 2011. In this study, we included 8874 the 10,228 participants. Diagnosis of GDM was determined using the criteria of the Japan Diabetes Society (JDS). The quality and quantity of social capital were measured with nine questions on a self-administered questionnaire during the second or third trimester. Using principal component analysis (PCA), we distinguished the following three components (indices) of social capital: (A) index of all nine questions about social capital, (B) index of emotional support and neighborhood trust and (C) index of generalized trust. The high factor loading variants of indices were as follows; (A) all nine variants, (B) five variants about emotional support and neighborhood trust and (C) two variants about generalized trust. Multivariate random effect modeling was used to calculate the odd ratios (ORs) for evaluating the association between these indices of social capital and the prevalence of GDM. This model was adjusted for baseline characteristics such as family income, BMI before pregnancy and smoking during pregnancy. RESULTS: Of the 8874 participants, 204 women developed GDM (2.30%). Multivariable logistic regression analysis showed that index B, the index of emotional support and neighborhood trust (adjusted OR: 0.651, 95% CI: 0.429, 0.987) was significantly and independently associated with the prevalence of GDM. CONCLUSIONS: We found that the 5-question index of emotional support and neighborhood trust is significantly associated with the prevalence of GDM during pregnancy.

Psychological distress during pregnancy in Miyagi after the Great East Japan Earthquake: The Japan Environment and Children's Study.

OBJECTIVE: To examine psychological distress among pregnant women in Miyagi prefecture which was directly affected by the Great East Japan Earthquake and tsunami and compare other areas of Japan that were less damaged. METHODS: This study was conducted in conjunction with the Japan Environment and Children's Study (JECS). We examined 10,129 Japanese women using the primary fixed data of the JECS. The Kessler 6-item psychological distress scale (K6) was administered to 7473 eligible women including 998 in Miyagi unit center ('Miyagi UC') and 6475 in the other unit centers ('13UCs'). We compared the prevalence and the risk of distress (K6 ≥ 13) during pregnancy in 'Miyagi UC' and '13UCs'. RESULTS: More women in 'Miyagi UC' (4.9%) suffered psychological distress, compared with '13UCs' (3.1%) (p<0.001). A significantly higher prevalence of women in 'Miyagi UC' (55.5%) had experienced negative life events, whereas '13UCs' showed 42.7% (p<0.0001). In multivariable logistic analyses adjusted for baseline characteristics, there was a significant regional difference of psychological distress (adjusted odds ratio; aOR in Miyagi UC=1.488; 95%CI, 1.059-2.090). After further adjusting for negative life events, the association was diminished (aOR=1.338; 95%CI, 0.949-1.884). LIMITATIONS: The JECS had no data before the earthquake and the extent of damage was not investigated. Possible regional representativeness is also a limitation. CONCLUSION: After the Great East Japan Earthquake, the prevalence of pregnant women with psychological distress (K6 ≥ 13) were high in Miyagi prefecture. Especially in the coastal area directly affected by tsunami, it is high with or without negative life events experienced.

Secretin receptor involvement in prion-infected cells and animals.

The cellular mechanisms behind prion biosynthesis and metabolism remain unclear. Here we show that secretin signaling via the secretin receptor regulates abnormal prion protein formation in prion-infected cells. Animal studies demonstrate that secretin receptor deficiency slightly, but significantly, prolongs incubation time in female but not male mice. This gender-specificity is consistent with our finding that prion-infected cells are derived from females. Therefore, our results provide initial insights into the reasons why age of disease onset in certain prion diseases is reported to occur slightly earlier in females than males.