BackgroundThere is global concern over significant threats from a wide variety of environmental hazards to which children face. Large-scale and long-term birth cohort studies are needed for better environmental management based on sound science. The primary objective of the Japan Environment and Children’s Study (JECS), a nation-wide birth cohort study that started its recruitment in January 2011, is to elucidate environmental factors that affect children’s health and development.Methods/DesignApproximately 100,000 expecting mothers who live in designated study areas will be recruited over a 3-year period from January 2011. Participating children will be followed until they reach 13 years of age. Exposure to environmental factors will be assessed by chemical analyses of bio-specimens (blood, cord blood, urine, breast milk, and hair), household environment measurements, and computational simulations using monitoring data (e.g. ambient air quality monitoring) as well as questionnaires. JECS’ priority outcomes include reproduction/pregnancy complications, congenital anomalies, neuropsychiatric disorders, immune system disorders, and metabolic/endocrine system disorders. Genetic factors, socioeconomic status, and lifestyle factors will also be examined as covariates and potential confounders. To maximize representativeness, we adopted provider-mediated community-based recruitment.DiscussionThrough JECS, chemical substances to which children are exposed during the fetal stage or early childhood will be identified. The JECS results will be translated to better risk assessment and management to provide healthy environment for next generations.

BackgroundThe Japan Environment and Children’s Study (JECS), known as Ecochil-Chosa in Japan, is a nationwide birth cohort study investigating the environmental factors that might affect children’s health and development. We report the baseline profiles of the participating mothers, fathers, and their children.MethodsFifteen Regional Centres located throughout Japan were responsible for recruiting women in early pregnancy living in their respective recruitment areas. Self-administered questionnaires and medical records were used to obtain such information as demographic factors, lifestyle, socioeconomic status, environmental exposure, medical history, and delivery information. In the period up to delivery, we collected bio-specimens, including blood, urine, hair, and umbilical cord blood. Fathers were also recruited, when accessible, and asked to fill in a questionnaire and to provide blood samples.ResultsThe total number of pregnancies resulting in delivery was 100,778, of which 51,402 (51.0%) involved program participation by male partners. Discounting pregnancies by the same woman, the study included 95,248 unique mothers and 49,189 unique fathers. The 100,778 pregnancies involved a total of 101,779 fetuses and resulted in 100,148 live births. The coverage of children in 2013 (the number of live births registered in JECS divided by the number of all live births within the study areas) was approximately 45%. Nevertheless, the data on the characteristics of the mothers and children we studied showed marked similarity to those obtained from Japan’s 2013 Vital Statistics Survey.ConclusionsBetween 2011 and 2014, we established one of the largest birth cohorts in the world.

The identity of the cellular mechanisms through which nitroglycerin (glyceryl trinitrate, GTN) elicits nitric oxide (NO)-based signaling to dilate blood vessels remains one of the longest standing foci of investigation and sources of controversy in cardiovascular biology. Recent evidence suggests an unexpected role for mitochondria. We show here that bioconversion by mitochondria of clinically relevant concentrations of GTN results in activation of guanylate cyclase, production of cGMP, vasodilation in vitro, and lowered blood pressure in vivo, which are eliminated by genetic deletion of the mitochondrial aldehyde dehydrogenase (mtALDH). In contrast, generation of vasoactivity from alternative nitro(so)-vasodilators is unaffected. In mtALDH ؊/؊ mice and their isolated vascular tissue, GTN bioactivity can still be generated, but only at substantially higher concentrations of GTN and by a mechanism that does not exhibit tolerance. Thus, mtALDH is necessary and sufficient for vasoactivity derived from therapeutic levels of GTN, and, more generally, mitochondria can serve as a source of NObased cellular signals that may originate independently of NO synthase activity.nitric oxide ͉ nitrite ͉ S-nitrosothiol ͉ nitrate tolerance T he ability of mammalian cells to convert the manmade organic nitrate, nitroglycerin (glyceryl trinitrate, GTN), to vasoactive nitric oxide (NO) or S-nitrosothiol (SNO) played a significant part in the discovery that NO or its equivalent functions as an endogenous physiological mediator (1, 2), and GTN has long served as a principal therapeutic agent for acute angina and congestive heart disease (3-7). Although multiple cellular activities mediating GTN metabolism have been characterized, the mechanisms that specifically subserve GTN bioactivation have remained elusive. Recent evidence indicates a central role for mitochondria in GTN bioactivation. In particular, it has been proposed that the mitochondrial aldehyde dehydrogenase (mtALDH), aldehyde dehydrogenase (ALDH) 2, may provide a principal enzymatic source of GTN-derived NO vasoactivity (through the intermediacy of mitochondrial nitrite) and that mechanism-based mtALDH inactivation contributes to GTN tolerance (8-10). However, this previously uncharacterized role for mitochondria in the generation of NO bioactivity remains unproven, and the centrality of mtALDH in GTN bioactivation in vivo has been disputed (5-7). The findings described in the present study establish that NO bioactivity originating in mitochondria and generated by mtALDH is necessary and sufficient to account for the vasoactivity of clinically relevant concentrations of GTN. Our results suggest, in addition, that inactivation of mtALDH is a principal component of mechanism-based GTN tolerance. Materials and Methods mtALDH ؊/؊ Mice. The generation of mtALDHϪ/Ϫ mice has been described in ref. 11. Wild-type (C57BL͞6) and mtALDH Ϫ/Ϫ mice used for comparative measurements were gender-and agematched (3-4 months). All procedures were approved by the Institutional Animal Care and...