Lactational Exposure to Polybrominated Diphenyl Ethers and Its Relation to Social and Emotional Development among Toddlers

Background: Polybrominated diphenyl ethers (PBDEs) have been widely used as flame retardants and are ubiquitous environmental contaminants. PBDEs have been linked to adverse neurodevelopment in animals and humans

Brominated Flame Retardants in Breast Milk and Behavioral and Cognitive Development at 36 Months

Polybrominated diphenyl ethers (PBDEs) are persistent flame retardants found in the environment, in household dust, and in humans. Breast feeding is a prominent route of exposure in infancy. PBDEs adversely affect neurodevelopment in animals. Here, we estimate associations between PBDEs in breast milk and behavior and cognitive skills in children at 36 months of age

Citrullinated vimentin presented on MHC-II in tumor cells is a target for CD4+ T-cell-mediated antitumor immunity

Stressful conditions in the harsh tumor microenvironment induce autophagy in cancer cells as a mechanism to promote their survival. However, autophagy also causes post-translational modification of proteins that are recognized by the immune system. In particular, modified self-antigens can trigger CD4(+) T-cell responses that might be exploited to boost antitumor immune defenses. In this study, we investigated the ability of CD4 cells to target tumor-specific self-antigens modified by citrullination, which converts arginine residues in proteins to citrulline. Focusing on the intermediate filament protein vimentin, which is frequently citrullinated in cells during epithelial-to-mesenchymal transition of metastasizing epithelial tumors, we generated citrullinated vimentin peptides for immunization experiments in mice. Immunization with these peptides induced IFN?- and granzyme B-secreting CD4 T cells in response to autophagic tumor targets. Remarkably, a single immunization with modified peptide, up to 14 days after tumor implant, resulted in long-term survival in 60% to 90% of animals with no associated toxicity. This antitumor response was dependent on CD4 cells and not CD8(+) T cells. These results show how CD4 cells can mediate potent antitumor responses against modified self-epitopes presented on tumor cells, and they illustrate for the first time how the citrullinated peptides may offer especially attractive vaccine targets for cancer therapy

Lactational exposure to polychlorinated biphenyls, dichlorodiphenyltrichloroethane, and dichlorodiphenyldichloroethylene and infant growth: an analysis of the Pregnancy, Infection, and Nutrition Babies Study: Lactational exposure to persistent environmental pollutants

Polychlorinated biphenyls (PCBs), 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (p,p’-DDT) and 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene (p,p’-DDE), the most stable metabolite of p,p’-DDT, are persistent organic pollutants and environmental endocrine disruptors. Infant exposure to these chemicals through breast feeding may influence children’s growth, but this potential adverse effect could be complicated by the co-existing benefits of breast feeding. This study examined the associations between lactational exposure to these chemicals and infant growth in the first 12 months by using data from the Pregnancy, Infection and Nutrition Babies Study in central North Carolina, United States, 2004–2006. The study population was restricted to the infants who were breastfed for 6 months or longer. PCBs, p,p’-DDT and p,p’-DDE were measured in breast milk at 3 months postpartum. Lactational exposure through 12 months was estimated as the product of chemical concentrations and the duration of breast feeding. The infant’s weight and length were recorded from the medical record for each routine pediatric well-child visit in the first 12 months. Women-child pairs who breastfed for 6 months or longer and returned the growth card (n=210), were included in the study. Linear mixed effects models were used to assess the associations between chemical concentrations in breast milk and longitudinal infant weight and length measurements in the first 6 months. Multivariable linear regression models were used to assess the relationships between lactational exposure to chemicals through 12 months and the z-scores of infant weight, length and weight-for-length at 12 months. Overall, no association was observed. Breast feeding for 6 months or longer, with lactational exposure to PCBs, p,p’-DDT and p,p’-DDE at the low background level concentrations studied here, results in no measurable influence on infant growth in the first 12 months

Lactational Exposure to Polychlorinated Biphenyls, Dichlorodiphenyltrichloroethane, and Dichlorodiphenyldichloroethylene and Infant Neurodevelopment: An Analysis of the Pregnancy, Infection, and Nutrition Babies Study

BackgroundPolychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT) are persistent, bioaccumulative, and toxic pollutants that were broadly used in the United States until the 1970s. Common exposure to PCBs, DDT, and dichlorodiphenyldichloroethylene (DDE), the most stable metabolite of DDT, may influence children’s neurodevelopment, but study results are not consistent.ObjectivesWe examined the associations between lactational exposure to PCBs, DDT, and DDE and infant development at 12 months, using data from the Pregnancy, Infection, and Nutrition Babies Study, 2004–2006.MethodsWe measured PCBs, DDT, and DDE in breast milk at the third month postpartum. Lactational exposure of these chemicals was estimated by the product of chemical concentrations and the duration of breast-feeding. Infant development at 12 months of age was measured by the Mullen Scales of Early Learning (n = 231) and the Short Form: Level I (infant) of the MacArthur–Bates Communicative Development Indices (n = 218).ResultsNo consistent associations were observed between lactational exposure to PCBs, DDT, and DDE through the first 12 months and the measures of infant development. However, DDE was associated with scoring below average on the gross motor scale of the Mullen among males only (adjusted odds ratio = 1.9; 95% confidence interval, 1.1–3.3).ConclusionInfant neurodevelopment at 12 months of age was not impaired by PCBs, DDT, and DDE at the concentrations measured here, in combination with benefits from long duration of breast-feeding in this population