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Box Elder, WA, United States

Brown S.E.,Center on Human Development and Disability | Guralnick M.J.,University of Washington
Infants and Young Children | Year: 2012

With almost universal ratification of the Convention on the Rights of the Child and the growing number of States Parties that have signed or ratified the Convention on the Rights of Persons with Disabilities, the majority of countries in the world have now committed to implementing the human rights articulated in these treaties. In this article, first, we provide an overview of both Conventions, highlight the articles in the treaties that are relevant to early intervention for infants and young children with disabilities, and describe the specific duties required of States Parties to ensure compliance including international cooperation. Second, a series of early intervention action principles is put forward that can help States Parties translate the underlying values of the Conventions into practice. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source


Curtis B.,Infant Primate Research Laboratory | Curtis B.,Center on Human Development and Disability | Liberato N.,Infant Primate Research Laboratory | Liberato N.,Center on Human Development and Disability | And 22 more authors.
Environmental Health Perspectives | Year: 2015

Background: In the 1990s, the mercury-based preservative thimerosal was used in most pediatric vaccines. Although there are currently only two thimerosal-containing vaccines (TCVs) recommended for pediatric use, parental perceptions that vaccines pose safety concerns are affecting vaccination rates, particularly in light of the much expanded and more complex schedule in place today. oBjectives: The objective of this study was to examine the safety of pediatric vaccine schedules in a non-human primate model. Methods: We administered vaccines to six groups of infant male rhesus macaques (n = 12–16/ group) using a standardized thimerosal dose where appropriate. Study groups included the recommended 1990s Pediatric vaccine schedule, an accelerated 1990s Primate schedule with or without the measles–mumps–rubella (MMR) vaccine, the MMR vaccine only, and the expanded 2008 schedule. We administered saline injections to age-matched control animals (n = 16). Infant development was assessed from birth to 12 months of age by examining the acquisition of neonatal reflexes, the development of object concept permanence (OCP), computerized tests of discrimination learning, and infant social behavior. Data were analyzed using analysis of variance, multi level modeling, and survival analyses, where appropriate. results: We observed no group differences in the acquisition of OCP. During discrimination learning, animals receiving TCVs had improved performance on reversal testing, although some of these same animals showed poorer performance in subsequent learning-set testing. Analysis of social and non social behaviors identified few instances of negative behaviors across the entire infancy period. Although some group differences in specific behaviors were reported at 2 months of age, by 12 months all infants, irrespective of vaccination status, had developed the typical repertoire of macaque behaviors. conclusions: This comprehensive 5-year case–control study, which closely examined the effects of pediatric vaccines on early primate development, provided no consistent evidence of neuro -developmental deficits or aberrant behavior in vaccinated animals. © 2015, Public Health Services, US Dept of Health and Human Services. All rights reserved. Source


Su W.,University of Washington | Kang J.,University of Washington | Sopher B.,University of Washington | Gillespie J.,University of Washington | And 8 more authors.
Journal of Neurochemistry | Year: 2016

Microglia are a specialized population of myeloid cells that mediate CNS innate immune responses. Efforts to identify the cellular and molecular mechanisms that regulate microglia behaviors have been hampered by the lack of effective tools for manipulating gene expression. Cultured microglia are refractory to most chemical and electrical transfection methods, yielding little or no gene delivery and causing toxicity and/or inflammatory activation. Recombinant adeno-associated viral (rAAVs) vectors are non-enveloped, single-stranded DNA vectors commonly used to transduce many primary cell types and tissues. In this study, we evaluated the feasibility and efficiency of utilizing rAAV serotype 2 (rAAV2) to modulate gene expression in cultured microglia. rAAV2 yields high transduction and causes minimal toxicity or inflammatory response in both neonatal and adult microglia. To demonstrate that rAAV transduction can induce functional protein expression, we used rAAV2 expressing Cre recombinase to successfully excise a LoxP-flanked miR155 gene in cultured microglia. We further evaluated rAAV serotypes 5, 6, 8, and 9, and observed that all efficiently transduced cultured microglia to varying degrees of success and caused little or no alteration in inflammatory gene expression. These results provide strong encouragement for the application of rAAV-mediated gene expression in microglia for mechanistic and therapeutic purposes. Neonatal microglia are functionally distinct from adult microglia, although the majority of in vitro studies utilize rodent neonatal microglia cultures because of difficulties of culturing adult cells. In addition, cultured microglia are refractory to most methods for modifying gene expression. Here, we developed a novel protocol for culturing adult microglia and evaluated the feasibility and efficiency of utilizing Recombinant Adeno-Associated Virus (rAAV) to modulate gene expression in cultured microglia. Neonatal microglia are functionally distinct from adult microglia, although the majority of in vitro studies utilize rodent neonatal microglia cultures because of difficulties of culturing adult cells. In addition, cultured microglia are refractory to most methods for modifying gene expression. Here, we developed a novel protocol for culturing adult microglia and evaluated the feasibility and efficiency of utilizing Recombinant Adeno-Associated Virus (rAAV) to modulate gene expression in cultured microglia. This article is part of the Special Issue "Neuroinflammation - A Two Way Street Directing CNS Injury and Repair". © 2015 International Society for Neurochemistry. Source


Robinson J.F.,University of Washington | Robinson J.F.,Institute for Risk Analysis and Risk Communication | Robinson J.F.,Center for Child Environmental Health Risks Research | Guerrette Z.,University of Washington | And 13 more authors.
Birth Defects Research Part B - Developmental and Reproductive Toxicology | Year: 2010

BACKGROUND: Aberrations during neurulation due to genetic and/or environmental factors underlie a variety of adverse developmental outcomes, including neural tube defects (NTDs). Methylmercury (MeHg) is a developmental neurotoxicant and teratogen that perturbs a wide range of biological processes/pathways in animal models, including those involved in early gestation (e.g., cell cycle, cell differentiation). Yet, the relationship between these MeHg-linked effects and changes in gestational development remains unresolved. Specifically, current information lacks mechanistic comparisons across dose or time for MeHg exposure during neurulation. These detailed investigations are crucial for identifying sensitive indicators of toxicity and for risk assessment applications. METHODS: Using a systems-based toxicogenomic approach, we examined dose- and time-dependent effects of MeHg on gene expression in C57BL/6 mouse embryos during cranial neural tube closure, assessing for significantly altered genes and associated Gene Ontology (GO) biological processes. Using the GO-based application GO-Quant, we quantitatively assessed dose- and time-dependent effects on gene expression within enriched GO biological processes impacted by MeHg. RESULTS: We observed MeHg to significantly alter expression of 883 genes, including several genes (e.g., Vangl2, Celsr1, Ptk7, Twist, Tcf7) previously characterized to be crucial for neural tube development. Significantly altered genes were associated with development cell adhesion, cell cycle, and cell differentiation-related GO biological processes. CONCLUSIONS: Our results suggest that MeHg-induced impacts within these biological processes during gestational development may underlie MeHg-induced teratogenic and neurodevelopmental toxicity outcomes. © 2010 Wiley-Liss, Inc. Source

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