Molecular and Antigenic Characterization of Reassortant H3N2 Viruses from Turkeys with a Unique Constellation of Pandemic H1N1 Internal Genes

Triple reassortant (TR) H3N2 influenza viruses cause varying degrees of loss in egg production in breeder turkeys. In this study we characterized TR H3N2 viruses isolated from three breeder turkey farms diagnosed with a drop in egg production. The eight gene segments of the virus isolated from the first case submission (FAV-003) were all of TR H3N2 lineage. However, viruses from the two subsequent case submissions (FAV-009 and FAV-010) were unique reassortants with PB2, PA, nucleoprotein (NP) and matrix (M) gene segments from 2009 pandemic H1N1 and the remaining gene segments from TR H3N2. Phylogenetic analysis of the HA and NA genes placed the 3 virus isolates in 2 separate clades within cluster IV of TR H3N2 viruses. Birds from the latter two affected farms had been vaccinated with a H3N4 oil emulsion vaccine prior to the outbreak. The HAl subunit of the H3N4 vaccine strain had only a predicted amino acid identity of 79% with the isolate from FAV-003 and 80% for the isolates from FAV-009 and FAV-0010. By comparison, the predicted amino acid sequence identity between a prototype TR H3N2 cluster IV virus A/Sw/ON/33853/2005 and the three turkey isolates from this study was 95% while the identity between FAV-003 and FAV-009/10 isolates was 91%. When the previously identified antigenic sites A, B, C, D and E of HA1 were examined, isolates from FAV-003 and FAV-009/10 had a total of 19 and 16 amino acid substitutions respectively when compared with the H3N4 vaccine strain. These changes corresponded with the failure of the sera collected from turkeys that received this vaccine to neutralize any of the above three isolates in vitro

Development of pharyngeal arch arteries in early mouse embryo

The formation and transformation of the pharyngeal arch arteries in the mouse embryo, from 8.5 to 13 days of gestation (DG), was observed using scanning electron microscopy of vascular casts and graphic reconstruction of 1-µm serial epoxy-resin sections. Late in 8.5–9DG (12 somites), the paired ventral aortae were connected to the dorsal aortae via a loop anterior to the foregut which we call the ‘primitive aortic arch’, as in the chick embryo. The primitive aortic arch extended cranio-caudally to be transformed into the primitive internal carotid artery, which in turn gave rise to the primitive maxillary artery and the arteries supplying the brain. The second pharyngeal arch artery (PAA) appeared late in 9–9.5DG (16–17 somites), and the ventral aorta bent dorsolaterally to form the first PAA anterior to the first pharyngeal pouch by early in 9.5–10DG (21–23 somites). The third PAA appeared early in 9.5–10DG (21–23 somites), the fourth late in 9.5–10DG (27–29 somites), and the sixth at 10DG (31–34 somites). By 10.5DG (35–39 somites), the first and second PAAs had been transformed into other arteries, and the third, fourth and sixth PAAs had developed well, though the PAA system still exhibited bilateral symmetry. By 13DG, the right sixth PAA had disappeared, and the remaining PAAs formed an aortic-arch system that was almost of the adult type

Effects of prenatal phthalate exposure on thyroid hormone levels, mental and psychomotor development of infants : The Hokkaido Study on Environment and Children's Health

Di (2-ethylhexyl) phthalate (DEHP) is commonly used phthalates and concerns of adverse effects of prenatal DEHP exposure on neonatal thyroid hormone (TH) and neurodevelopment are increasing. However, there is no report regarding association between prenatal DEHP exposure and infant neurodevelopment including TH levels in Japanese population. Thus the aim of present study was to evaluate the associations between prenatal DEHP exposure and mental and psychomotor development of infants 6 and 18 months along with investigating influence on neonatal free thyroxine (FT4) and thyroid stimulating hormone (TSH) levels in the prospective birth cohort study. Maternal blood samples collected between 23-41 weeks of gestation was analyzed for mono (2-ethylhexyl) phthalate (MEHP), metabolite of DEHP levels. Neonatal FT4 and TSH were obtained from mass screening data. Infant neurodevelopment was assessed by Bayley Scale of Infant Development second edition at 6 and 18 month of age. For the final analysis, 328 participants were included. The median levels of maternal MEHP was 10.6 ng/ml, neonatal TSH and FT4 was 2.20 μU/ml and 2.03 ng/ml, respectively. We did not find any associations between prenatal DEHP exposure and neonatal TH levels or infant mental and psychomotor development at 6 and 18 month. In this study, prenatal DEHP exposure did not show adverse effects on infant TH levels or mental and psychomotor development in early life stage. However, our previous study revealed negative effects of prenatal DEHP exposure on sex hormone levels, continuous investigation on neurodevelopment in later life in association with prenatal DEHP exposure is necessary

Sex-specific differences in effect of prenatal exposure to dioxin-like compounds on neurodevelopment in Japanese children : Sapporo cohort study

BACKGROUND: Consistent reports are not available on the effects of dioxin-like polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins (PCDD)/ polychlorinated dibenzofurans (PCDF) (dioxin-like compounds [DLCs]) on child neurodevelopment. Further, the effect of background-level exposure to individual DLC isomers is not known. OBJECTIVES: We carried out the Sapporo cohort study to evaluate the effect of prenatal exposure to each DLC isomer on child neurodevelopment at 6 and 18 months of age, and assessed sex-specific differences in these effects. METHODS: The levels of all and each individual DLC isomers were estimated in maternal peripheral blood. Neurodevelopment was evaluated using the Bayley Scales of Infant Development-2nd Edition for 6-month-old infants (n = 190) and 18-month-old children (n = 121). RESULTS: In male children, levels of 10 DLC isomers were significantly negatively associated with the Psychomotor Developmental Index (PDI) at 6 months of age after adjustment for potential confounding variables. However, at 18 months of age, these associations were absent. In female children, the level of only one DLC isomer was significantly negatively associated with PDI at 6 months of age. However, in contrast to the male children, the levels of six DLC isomers in 18-month-old female children were significantly positively associated with the Mental Developmental Index. CONCLUSIONS: These findings indicate that adverse neurodevelopmental effects of prenatal background-level exposure to DLCs may be stronger in male children

Association between maternal antenatal depression and infant development : a hospital-based prospective cohort study

Objective To examine the association between antenatal depression and infant development after controlling for confounding factors. Methods A hospital-based prospective cohort study (Hokkaido Study on Environment and Children’s Health) was conducted between July 2002 and October 2005 in Sapporo, Japan. Of 309 mothers who delivered at Sapporo Toho Hospital during the study period and who agreed with the clinical assessment of depression, 154 mother–infant pairs were eligible for analysis. Antenatal depression was assessed between the second and third trimesters using the Edinburgh Postnatal Depression Scale (EPDS), and infant development was assessed at 6 months by the Bayley Scales of Infant Development II (BSID-II). Data on potential confounders, including socioeconomic status, birth complications, postnatal depression and child care environment, were obtained from medical records and self-administered questionnaires. Univariable and multivariable analyses were conducted in which the EPDS score was entered as an independent variable and the BSID-II scores as a dependent variable, adjusting for confounders. Results Although the antenatal EPDS score tended to be related to the BSID-II score in the univariable analysis, this correlation was lost in the multivariable analysis. However, based on a series of linear regression analyses, antenatal depression was found to be significantly related to shorter gestational age (β = −0.25, 95 % confidence interval (CI) [−1.20, −0.17]), and shorter gestational age was significantly related to a lower BSID-II (mental development) score (β = 0.23, 95 % CI [0.00, 0.00]). Conclusions Gestational age is an important confounder in the association between maternal antenatal depression and infant development. A delay in infant development may be related to a shorter gestational period caused by maternal depression during pregnancy

Association between Maternal Exposure to di(2-ethylhexyl) Phthalate and Reproductive Hormone Levels in Fetal Blood: The Hokkaido Study on Environment and Children's Health

Prenatal di(2-ethylhexyl) phthalate (DEHP) exposure can produce reproductive toxicity in animal models. Only limited data exist from human studies on maternal DEHP exposure and its effects on infants. We aimed to examine the associations between DEHP exposure in utero and reproductive hormone levels in cord blood. Between 2002 and 2005, 514 pregnant women agreed to participate in the Hokkaido Study Sapporo Cohort. Maternal blood samples were taken from 23–35 weeks of gestation and the concentration of the primary metabolite of DEHP, mono(2-ethylhexyl) phthalate (MEHP), was measured. Concentrations of infant reproductive hormones including estradiol (E2), total testosterone (T), and progesterone (P4), inhibin B, insulin-like factor 3 (INSL3), steroid hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone were measured from cord blood. Two hundred and two samples with both MEHP and hormones' data were included in statistical analysis. The participants completed a self-administered questionnaire regarding information on maternal characteristics. Gestational age, birth weight and infant sex were obtained from birth records. In an adjusted linear regression analysis fit to all study participants, maternal MEHP levels were found to be associated with reduced levels of T/E2, P4, and inhibin B. For the stratified analyses for sex, inverse associations between maternal MEHP levels T/E2, P4, inhibin B, and INSL3 were statistically significant for males only. In addition, the MEHP quartile model showed a significant p-value trend for P4, inhibin B, and INSL3 decrease in males. Since inhibin B and INSL3 are major secretory products of Sertoli and Leydig cell, respectively, the results of this study suggest that DEHP exposure in utero may have adverse effects on both Sertoli and Leydig cell development in males, which agrees with the results obtained from animal studies. Comprehensive studies investigating phthalates' exposure in humans, as well as their long-term effects on reproductive development are needed