O objetivo deste estudo é estimar o risco de infecção congênita pelo vírus da vacina contra rubéola e estimar o risco de ocorrência de aborto, baixo peso e prematuridade nas gestantes suscetíveis e imunes para rubéola identificando os fatores de risco associados a estes eventos. Embora não tenham havido manifestações clínicas compatíveis com SRC, observou-se uma ocorrência aumentada de baixo peso ao nascer e prematuridade entre os RN infectados quando comparados com as crianças não infectadas também nascidas de mães susceptíveis. No modelo final das análises utilizando a regressão logística multivariada, entretanto, a suscetibilidade para rubéola não esteve associada com a ocorrência de baixo peso e nem com prematuridade. Estes resultados sugerem que a recomendações de não vacinar gestantes para rubéola ainda deve ser mantida / The objective of this study is to evaluate the risk of congenital infection due to rubella vaccine virus and the occurrence of premature labor, miscarriage, and low birth weight in susceptible and immune pregnant women vaccinated during pregnancy, identifying the risk factors associated. We observe a high incidence of low birth weight and prematurity in the infected newborns, when compared with the children not infected, also born of susceptible mothers. In the final model of the logistic regression we didn't find association with rubella susceptibility and the predictors miscarriage, low birth weight and premature labor. These results suggest that the recommendations to not vaccinate pregnant women against rubella must be sustained

O objetivo deste estudo é estimar o risco de infecção congênita pelo vírus da vacina contra rubéola e estimar o risco de ocorrência de aborto, baixo peso e prematuridade nas gestantes suscetíveis e imunes para rubéola identificando os fatores de risco associados a estes eventos. Embora não tenham havido manifestações clínicas compatíveis com SRC, observou-se uma ocorrência aumentada de baixo peso ao nascer e prematuridade entre os RN infectados quando comparados com as crianças não infectadas também nascidas de mães susceptíveis. No modelo final das análises utilizando a regressão logística multivariada, entretanto, a suscetibilidade para rubéola não esteve associada com a ocorrência de baixo peso e nem com prematuridade. Estes resultados sugerem que a recomendações de não vacinar gestantes para rubéola ainda deve ser mantida / The objective of this study is to evaluate the risk of congenital infection due to rubella vaccine virus and the occurrence of premature labor, miscarriage, and low birth weight in susceptible and immune pregnant women vaccinated during pregnancy, identifying the risk factors associated. We observe a high incidence of low birth weight and prematurity in the infected newborns, when compared with the children not infected, also born of susceptible mothers. In the final model of the logistic regression we didn't find association with rubella susceptibility and the predictors miscarriage, low birth weight and premature labor. These results suggest that the recommendations to not vaccinate pregnant women against rubella must be sustained

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Rehabilitation and education are faced with the growing need for adequate and appropriate assessment tools for over 9,000 congenitally deaf-blind persons in this country. These tools are needed to help form the basis for evaluation of these clients/students so that programs appropriate to their specific needs can be determined. In the past, assessment of the functional development of this population has been based on tests standardized on populations of non-handicapped individuals. These measuring primarily language abilities, and experiential factors. Observational procedures can examine the spontaneous behavior of subjects over a long period of time. This is an alternative to standardized instruments. One of these in current use is the Basic Life Skills Screening Inventory. This instrument was developed in 1982 for the purpose of assisting educators and counselors in establishing the readiness of deaf-blind, developmentally disabled clients/students for vocational and life skills training. Though useful in its original form, this instrument has two major limitations. One is the fact that the rater is given only limited choices, resulting in a ceiling effect and a pronounced skew of many of its scales. Another limitation is its lengthy 283 item format, requiring too much administration time to be practical on a daily basis. The present study focused on making needed modifications in this instrument that would help alleviate these limitations, and continue to maintain high psychometric properties within the instrument. In doing this, rater choices were expanded from three (3) to five (5) column headings, and the instrument was reduced from 283 items to 145 items. This study was designed to answer the following questions: (1) Can the Basic Life Skills Screening Inventory be modified in such a way as to give the rater a greater response choice, thus allowing for a more refined assessment? (2) Can the 283 item, Basic Life Skills Screening Inventory be shortened by approximately 50%, to allow for an easier and more practical administration, and continue to maintain high psychometric properties? Results indicate that, despite the modifications, a very high overall consistency among the items was maintained with a total average alpha of 9935.5.

Estudamos, através de modelagem matemática, aspectos estacionários, espaciais e temporais relacionados à propagação e controle de doenças infecciosas de transmissão direta por contato pessoa-a-pessoa. Elaboramos modelos matemáticos determinísticos fundamentados no princípio de ação de massas em Epidemiologia, levando em consideração a simetria no número de contatos entre suscetíveis e infectados, o que nos permitiu estimar a taxa per capita de contatos potencialmente infectantes e, por conseguinte, a força de infecção e os possíveis efeitos de diferentes programas de vacinação. O desenvolvimento do modelo de estado estacionário foi feito com base em dados sorológicos de rubéola (Azevedo Neto 1992) para uma população que ainda não havia sido imunizada por meio de vacinação. Analisamos, então, o efeito de três diferentes esquemas de vacinação para a rubéola, nos seguintes intervalos de idade: de 1 a 2 anos, de 7 a 8 anos e de 14 a 15 anos. A incerteza estatística na idade média de infecção foi estimada com o auxílio do método de Monte Carlo e tal metodologia foi aplicada a dados de varicela e hepatite A. Estudamos também o aspecto espacial, com a inclusão da variável distância na formulação de um modelo SIR e análise da influência do alcance de interação entre indivíduos. E, através do estudo da força de infecção em função da idade e do tempo, pudemos analisar, de modo qualitativo, diferentes cenários na evolução temporal de uma doença infecciosa. / We have studied, based on mathematical modelling, stationary, spatial and temporal features related to the propagation and control of directly transmitted infectious diseases through person-to-person contact. We have developed deterministic mathematical models founded on the mass-action principle of Epidemiology, taking into account the symmetry of contacts among susceptible and infectious individuals. Such symmetry enabled us to estimate the potentially infective per capita contact rate and, therefore, the force of infection and the possible effects of different vaccination programmes. The steady state modelling has been based on rubella serological data of a non-immunized population (Azevedo Neto 1992) and we have analysed three different vaccination schemes against rubella in the following age intervals: from 1 to 2 years of age, from 7 to 8 years of age, and from 14 to 15 years of age. The serological data variability has been considered in the estimation of the statistical uncertainty of the average age at infection by means of the Monte Carlo method and we have applied this methodology to varicella and hepatitis A data. The spatial feature in a SIR model has been studied with the analysis of the influence of the interaction range among individuals. We have also studied the force of infection as a function of age and time and we have analysed, in a qualitative way, different situations in the time evolution of an infectious disease.

INTRODUÇÃO: Em 1999 e 2000, a ocorrência de surtos de rubéola, com maior acometimento entre adultos jovens, refletiu no aumento da síndrome da rubéola congênita. Como estratégia de controle da doença, foram realizadas campanhas de vacinação contra a rubéola em mulheres em idade fértil em vários Estados do País. Em razão das controvérsias existentes na literatura geradas quanto ao emprego da vacina de vírus vivos atenuados em gestantes, não se recomendou sua utilização durante a gravidez e até um mês após a aplicação da vacina. No entanto, 6.473 mulheres foram inadvertidamente vacinadas no Estado de São Paulo, sendo encaminhadas a serviços de referência para acompanhamento dessas gestações, dentre eles, o HCFMUSP. OBJETIVO: Este estudo buscou descrever as características clínicas e epidemiológicas das gestantes atendidas no HCFMUSP e obter os resultados dessas gestações. MÉTODO: Foi realizado um estudo epidemiológico descritivo, utilizando-se como fonte de dados as notificações das gestantes inadvertidamente vacinadas contra a rubéola e atendidas no HCFMUSP entre novembro de 2001 a dezembro de 2002. Para obter o desfecho das gestações, utilizou-se a base de dados dos nascidos vivos do Município de São Paulo (SINASC). RESULTADOS: No HCMFUSP, foram atendidas e notificadas 409 gestantes. Destas, 49,1% foram vacinadas no primeiro mês de gravidez e 26,2% engravidaram até um mês após a vacinação. Em relação a condição sorológica durante o pré-natal, 16,9% das gestantes apresentaram sorologia reagente para rubéola. Do relacionamento com a base de dados do SINASC, foram localizados os dados do parto de 63,3% das gestantes, sendo detectadas duas malformações congênitas no SINASC e um abortamento, porém, não se pode atribuir estes resultados à vacina, pois, as sorologias das mães não permitem determinar se estas mulheres eram realmente suscetíveis. CONSIDERAÇÕES FINAIS: O estudo apresentou o fluxo de informação estabelecido frente a um evento inusitado. Além disso, o uso de bases de dados secundárias contribuiu para o aprimoramento dos dados coletados, resultando na melhora da qualidade das informações. Os Núcleos de Epidemiologia Hospitalar são fundamentais na articulação entre a equipe assistencial e o Sistema de Vigilância e colaboram para discussão na padronização de Sistemas de Informação para permitir melhor integração entre as informações geradas pelos Serviços de Saúde. / INTRODUCTION: In the years 1999 and 2000, rubella outbreaks reaching mostly young adults resulted in an increased number of cases of Congenital Rubella Syndrome in Brazil. State Vaccination Campaigns aiming at women at childbearing age were promoted around the country to control the disease, recommending that vaccination of pregnant women should be avoided and pregnancy should be postponed for at least a month after vaccination. Despite the recommendations, 6.473 pregnant women were accidentally vaccinated in the State of São Paulo and therefore sent to reference obstetrical services for prenatal care. A study was conducted to describe the cases assisted at the University of São Paulo, School of Medicine, General Hospital and notified to Public Health and also to obtain information on the pregnancy outcomes. METHODS: This descriptive epidemiological study used notification by the Hospital Epidemiology Service as source of information on pregnant women accidentally vaccinated against rubella that received care from November 2001 to December 2002 at the School of Medicine, General Hospital. The City of São Paulo Newborn Database was searched for pregnancy outcomes. RESULTS: Among the 409 notified cases, 49,1% were women accidentally vaccinated during fist trimester of pregnancy and 26,2% women that became pregnant within less than a month after vaccination. Positive serological tests were found in 16,9% of women during prenatal care. Newborn data base search yielded pregnancy outcome for 63,3%. The findings of 2 cases of Congenital Rubella Syndrome and 1miscarriage cannot be surely attributed to vaccination because immediate previous immunization status was unknown. CONCLUSIONS: The study described the information flow established for an unexpected adverse event and the use of secondary data to improve quality of information. Hospital Epidemiology Services have a fundamental role in connecting health assisting professionals to Public Surveillance Systems and in setting standards for information generated by Health Assistance.

Ca2+, a signal for death and life, is closely involved in the regulation of numerous important cellular events. Ca2+ carries out its function through its binding to Ca2+-receptors or Ca2+-binding proteins. The EF-hand protein, with a helix-loop-helix Ca2+-binding motif, constitutes one of the largest protein families. To facilitate our understanding of the role of Ca2+ in biological systems (denoted as calciomics) using genomic information, an improved pattern search method (http://www.chemistry.gsu.edu/faculty/Yang/Calciomics.htm) for the identification of EF-hand and EF-like Ca2+-binding proteins was developed. This fast and robust method allows us to analyze putative EF-hand proteins at the genome-wide level and further visualize the evolutionary scenario of the EF-hand protein family. This prediction method further enables us to locate a putative viral EF-hand Ca2+-binding motif within the rubella virus nonstructural protease that cleaves the nonstructural protein precursor into two active replicase components. A novel grafting approach has been used to probe the metal-binding properties of this motif by engineering the predicted 12-residue Ca2+-coordinating loop into a non-Ca2+-binding scaffold protein, CD2 domain 1. Structural and conformational studies were further performed on a purified, bacterially-expressed NS protease minimal metal-binding domain spanning the Zn2+- and EF-hand Ca2+-binding motif. It was revealed that Ca2+ binding induced local conformational changes and increased thermal stability. Furthermore, functional studies were carried out using RUB infectious cDNA clone and replicon constructs. Our studies have shown that the Ca2+ binding loop played a structural role in the NS protease and was specifically required for optimal stability under physiological conditions. In addition, we have predicted and characterized a calmodulin-binding domain in the gap junction proteins connexin43 and connexin44. Peptides encompassing the CaM binding motifs were synthesized and their ability to bind CaM was determined using various biophysical approaches. Transient expression in HeLa cells of two mutant Cx43-EYFP constructs without the putative CaM-binding site eliminated the Ca2+-dependent inhibition of gap junction permeability. These results provide the first direct evidence that CaM binds to a specific region of the ubiquitous gap junction protein Cx43 and Cx44 in a Ca2+-dependent manner, providing a molecular basis for the well-characterized Ca2+-dependent inhibition of Cx43-containing gap junctions.

The ground work for this research thesis was completed seven years ago when the Dow Pharmaceutical Company selected Muncie, Indiana to test their new rubella vaccine. In the Fall of 1970, 311 seronegative elementary school children were innoculated with HPV-77, DK12 rubella vaccine. Of the 302 children who seroconverted, 98 were available for follow-up six years post innoculation. The participant's sera drawn six years previously was recovered in order to determine a six week and six year post innoculation titer on paired specimens. All 98 children, when retested, has measurable antibody. The geometric mean titer six years post innoculation was 55; a 14% decrease from the geometric titer of 64 six weeks after innoculation. At the six year point in time, there was at least a 9.2% incidence of subclinical reinfection, detected by a fourfold rise in the HI-titer, within the study group.Ball State UniversityMuncie, IN 47306

The rubella virus (RUB) capsid protein (C) is a multifunctional phosphoprotein with roles beyond encapsidation. It is able to rescue a large lethal deletion of the Q domain in the P150 replicase gene at a step in replication before detectable viral RNA synthesis, indicating a common function shared by RUB C and the Q domain. The goal of this dissertation was to use constructs containing the N-terminal 88 amino acids of RUB C, the region previously defined as the minimal region required for the rescue of Q domain mutants, to elucidate the function of RUB C in Q domain rescue and viral RNA synthesis. In the first specific aim, the rescue function of 1-88 RUB C and the importance of an arginine-rich cluster, R2, within 1-88 RUB C for rescue were confirmed. Rescue was not correlated with intracellular localization or phosphorylation status of RUB C. In the second specific aim, the involvement of RUB C in early events post-transfection with RUB RNA was analyzed. RUB C specifically protected RUB transcripts early post-transfection and protection required R2. However, it was concluded the protection observed was due to the encapsidation function of RUB C and not related to Q domain rescue. No differences in the translation of the RUB nonstructural proteins in the presence or absence of RUB C were observed. Interactions of RUB C with host cell proteins were analyzed. Although the interaction of RUB C with cellular p32 required the R2 cluster, both wild type (does not require RUB C for replication) and RQQ (requires RUB C for replication) Q domain bound p32, indicating interaction with this binding partner is not the basis of rescue. Using a human protein array phosphatidylinositol transfer protein alpha isoform (PITPα) was found to interact with RUB C but not its R2 mutant. However, co-immunoprecipitation experiments revealed that this protein binds both forms of RUB C. Although the mechanism behind the rescue of the RUB P150 Q domain by RUB C remains unknown, we propose a model that RUB C plays a role in generation of the virus replication complex in infected cells.

Thesis (M.S.P.H.)--University of South Florida, 2008. / Title from PDF of title page. Document formatted into pages; contains 58 pages. Includes bibliographical references.