Specificity and Sensitivity of Screening for Anti-HLA Antibodies in Kidney Allograft Dysfunction

BACKGROUND: Prospective testing for posttransplant circulating anti-HLA antibodies seems to be a critical noninvasive tool, but confirmatory data are lacking. MATERIALS AND METHODS: Over the last 3 years, peritubular capillary (PTC) C4d deposition was prospectively sought by an immunofluorescence technique applied to frozen tissue in biopsies obtained for allograft dysfunction. Screening for circulating anti-HLA class I/II alloantibodies (AlloAb) by the flow cytometric test was performed simultaneously. RESULTS: We evaluated 132 sets of biopsies and simultaneous serum samples. PTC C4d deposition was demonstrated in 15.9% (21/132) of biopsies. Circulating anti-HLA I/II AlloAb were detected in 25% (33/132) of serum samples. Employing receiver-operator characteristic (ROC) curves for all C4d-positive biopsies, screening for AlloAb showed a global specificity of 82% and sensitivity of 61.9%. When this analysis was restricted to biopsies obtained in the first month posttransplantation, the sensitivity increased to 81.8%, but the specificity decreased to 76.9%. After the first month posttransplantation, we observed sensitivity of 40.0% and a specificity of 86.4%. In the first month posttransplantation, all patients with a diagnosis of acute antibody-mediated rejection displayed circulating anti-HLA class I/II, but not always at the same time as the C4d-positive biopsy. CONCLUSIONS: In the first month posttransplantation, prospective monitoring of anti-HLA antibodies may be useful. The high sensitivity allows the identification of patients at risk, affording an earlier diagnosis of antibody-mediated rejection. After the first month, the test can be used to evaluate allograft dysfunction episodes, since positivity is highly suggestive of an antibody-mediated process.

A interacção oral na sala de aula como desafio ao professor de Língua Estrangeira

O presente relatório foi elaborado no âmbito do estágio de Prática Educativa I, II e III, do curso de 2.º ciclo do Mestrado em Ensino do Inglês e Francês ou Espanhol no Ensino Básico, da Escola Superior de Educação. Ao longo deste relatório reflicto sobre as minhas práticas, incidindo em dois aspectos basilares para a realização deste trabalho: o modo como se processam as estratégias que concorrem para que seja possível promover a interacção oral dos alunos em sala de aula, e consequente desenvolvimento da sua competência comunicativa em língua estrangeira; e a forma como planifiquei actividades assentes em recursos diversificados, nomeadamente, jogos, histórias, flashcards, vídeo, roleplay, canções e debate. De forma a documentar as minhas reflexões, faço uma análise a algumas planificações de aulas em que utilizei os recursos mencionados, incluindo algumas imagens ilustrativas desses momentos. Concluo o relatório tecendo algumas considerações finais sobre o percurso que tracei na qualidade de aluna deste mestrado e de futura professora, reflectindo sobre alguns aspectos que considero relevantes na construção da profissionalidade docente.

Perspetivas interdisciplinares na planificação didática de Línguas e Culturas Estrangeiras

O presente Relatório Final de Estágio concretiza-se num trabalho de reflexão crítica sobre as práticas realizadas como professora estagiária de Inglês e de Espanhol no âmbito das Unidades Curriculares de Prática Educativa I, II e III, do Curso de Mestrado em Ensino de Inglês e Francês ou Espanhol, da Escola Superior de Educação, do Instituto Politécnico do Porto. A problemática que se apresenta decorre da perspetiva de que o ensino e aprendizagem de uma língua estrangeira baseados na articulação entre disciplinas do currículo contribui para uma aprendizagem holística, desenvolvendo competências que permitem um entendimento geral e global dos fenómenos humanos proporcionando aos alunos a compreensão do saber escolar como um todo articulável, contribuindo para uma leitura lógica e completa da realidade. A sua concretização na sala de aula impõe que o professor planifique atividades e opte por estratégias de ensino e de aprendizagem diversificadas, onde convergem finalidades, conceitos e metodologias de diversas disciplinas do currículo. Assim, este trabalho descreve a planificação de práticas de ensino e aprendizagem de Inglês e Espanhol em articulação com os conteúdos e os objetivos da disciplina de Estudo do Meio no Primeiro Ciclo. A planificação de práticas de Inglês no Segundo Ciclo foi realizada em articulação com a disciplina de História e Geografia de Portugal, com base na metodologia de projeto. As opções adotadas na planificação didática são consideradas estratégicas para uma aprendizagem significativa. Palavras-chave: perspetiva interdisciplinar do ensino; planificação didática de línguas estrangeiras; compreensão integrada do saber escolar; aprendizagem por projeto

Evaluation of dengue NS1 antigen detection for diagnosis in public health laboratories, São Paulo State, 2009

The present work evaluated the diagnostic accuracy of detection of Dengue NS1 antigen employing two NS1 assays, an immunochromatographic assay and ELISA, in the diagnostic routine of Public Health laboratories. The results obtained with NS1 assay were compared with virus isolation and, in a subpopulation of cases, they were compared with the IgM-ELISA results obtained with convalescent samples. A total of 2,321 sera samples were analyzed by one of two NS1 techniques from March to October 2009. The samples were divided into five groups: groups I, II and III included samples tested by NS1 and virus isolation, and groups IV and V included patients with a first sample tested by NS1 and a second sample tested by IgM-ELISA. Sensitivity, specificity, positive and negative predictive values, Kappa Index and Kappa Concordance were calculated. The results showed that NS1 testing in groups I, II and III had high sensitivity (98.0%, 99.5% and 99.3%), and predictive values and Kappa index between 0.9 - 1.0. Groups IV and V only had Kappa Concordance calculated, since the samples were analyzed according to the presence of NS1 antigen or IgM antibody. Concordance of 92.1% was observed when comparing the results of NS1-negative samples with IgM-ELISA. Based on the findings, it is possible to suggest that the tests for NS1 detection may be important tools for monitoring the introduction and spread of Dengue serotypes.

The Role of Sensory Modulation Deficits and Behavioral Symptoms in a Diagnosis for Early Childhood

To contribute to the validation of the sensory and behavioral criteria for Regulation Disorders of Sensory Processing (RDSP) (DC:0-3R, 2005), this study examined a sample of toddlers in a clinical setting to analyze: (1) the severity of sensory modulation deficits and the behavioral symptoms of RDSP; (2) the associations between sensory and behavioral symptoms; and (3) the specific role of sensory modulation deficits in an RDSP diagnosis. Based on clinical observations, 78 toddlers were classified into two groups: toddlers with RDSP (N = 18) and those with‘‘other diagnoses in Axis I/II of the DC:0-3R’’ (OD3R; N = 60). The parents completed the Infant Toddler Sensory Profile and the Achenbach Checklist. The results revealed that the RDSP group had more severe sensory modulation deficits and specific behavioral symptoms; stronger, although not significant, associations between most sensory and behavioral symptoms; and a significant sensory modulation deficit effect. These findings support the validity of RDSP.

Validating Regulatory Sensory Processing Disorders Using the Sensory Profile and Child Behavior Checklist (CBCL 1 –5)

The objective was to validate Regulatory Sensory Processing Disorders’ criteria (DC:0-3R, 2005) using empirical data on the presence and severity of sensory modulation deficits and specific psychiatric symptoms in clinical samples. Sixty toddlers who attended a child mental health unit were diagnosed by a clinical team. The following two groups were created: toddlers with RSPD(N = 14) and those with ‘‘other diagnoses in Axis I/II of the DC:0-3R00(OD3R) (N = 46). Independently of the clinical process, parents completed the Infant Toddler Sensory Profile (as a checklist for sensory symptoms) and the Achenbach Behavior Checklist for ages 1/2–5 (CBCL 1/2–5). The scores from the two groups were compared. The results showed the following for the RSPD group: a higher number of affected sensory areas and patterns than in the OD3R group; a higher percentage of sensory deficits in specific sensory categories; and a higher severity of behavioral symptoms such as withdrawal, inattention, other externalizing problems and pervasive developmental problems in CBCL 1/2–5. The results confirmed our hypotheses by indicating a higher severity of sensory symptoms and identifying specific behavioral problems in children with RSPD. The results revealed convergent validity between the instruments and the diagnostic criteria for RSPD and supported the validity of RSPD as a unique diagnosis. The findings also suggested the importance of identifying sensory modulation deficits in order to develop an early intervention to enhance the sensory capacities of children who do not fully satisfy the criteria for some DSM-IV-TR disorders.

ISOLATION AND GENOTYPING OF Toxoplasma gondii IN SERONEGATIVE URBAN RATS AND PRESENCE OF ANTIBODIES IN COMMUNICATING DOGS IN BRAZIL

The role of rodents in the epidemiology of toxoplasmosis was investigated inLondrina, Paraná State, Brazil. One hundred and eighty-one Rattus rattus and one Mus musculus were caught in 37 places. Blood and tissues were collected and submitted to the indirect fluorescence antibody test (IFAT) and the bioassay. Serum samples from 61 contacting dogs were also collected. Sixteen rats (8.8%) were positive for Toxoplasma gondii, but just two of them were positive by serology and bioassay test. Antibodies were found in nine (4.9%) rats. Tissues of nine rats bioassayed were positive and four isolates were obtained. Restriction fragment length polymorphism (RFLP) analysis was performed using 12 markers (SAG1, SAG2, SAG2-alt, C22-8, C29-2, L358, PK1, BTUB, GRA6, SAG3, Apico, CS3). Genotyping revealed that the four strains isolated from this study have been isolated before in cats and chickens from Brazil. None of the isolates was identified like clonal archetypal T-types I, II, and III. The rats presented lower serologic Toxoplasma gondii prevalence (8.8%) compared to contacting dogs (70.5%).

Differences in Nevirapine Biotransformation as a Factor for its Sex-Dependent Dimorphic Profile of Adverse Drug Reactions

OBJECTIVES: Nevirapine is widely used for the treatment of HIV-1 infection; however, its chronic use has been associated with severe liver and skin toxicity. Women are at increased risk for these toxic events, but the reasons for the sex-related differences are unclear. Disparities in the biotransformation of nevirapine and the generation of toxic metabolites between men and women might be the underlying cause. The present work aimed to explore sex differences in nevirapine biotransformation as a potential factor in nevirapine-induced toxicity. METHODS: All included subjects were adults who had been receiving 400 mg of nevirapine once daily for at least 1 month. Blood samples were collected and the levels of nevirapine and its phase I metabolites were quantified by HPLC. Anthropometric and clinical data, and nevirapine metabolite profiles, were assessed for sex-related differences. RESULTS: A total of 52 patients were included (63% were men). Body weight was lower in women (P = 0.028) and female sex was associated with higher alkaline phosphatase (P = 0.036) and lactate dehydrogenase (P = 0.037) levels. The plasma concentrations of nevirapine (P = 0.030) and the metabolite 3-hydroxy-nevirapine (P = 0.035), as well as the proportions of the metabolites 12-hydroxy-nevirapine (P = 0.037) and 3-hydroxy-nevirapine (P = 0.001), were higher in women, when adjusted for body weight. CONCLUSIONS: There was a sex-dependent variation in nevirapine biotransformation, particularly in the generation of the 12-hydroxy-nevirapine and 3-hydroxy-nevirapine metabolites. These data are consistent with the sex-dependent formation of toxic reactive metabolites, which may contribute to the sex-dependent dimorphic profile of nevirapine toxicity.

O vírus da hepatite B na doença hepática alcoólica: avaliação clínica e bioquímica

Foram estudados prospectiva e seqüencialmente 107 pacientes com doença hepática alcoólica (DHA) crônica, sendo 83 casos de cirrose e 24de hepatite alcoólica. Além do etilismo, ingestão mínima de 70 gramas de etanol puro ao dia por período superior a sete anos, todos apresentaram disfunção hepatocelular. De acordo com o perfil sorológico para o VHB os pacientes foram alocados em quatro grupos a saber: grupo I infectados: AgHBs e anti-HBc positivos; grupo II imunes: anti-HBs e anti-HBc positivos; grupo III sem marcadores do VHB: AgHBs, anti-HBc e anti-HBs negativos; grupo IV anti-HBc positivo isoladamente. A prevalência de infecção pelo VHB na DHA foi alta: 42,06% apesar dos índices pouco elevados de imunidade: 26,17% sugerindo que na DHA ocorre maior exposição ao VHB com resposta imunológica deficiente. A análise dos parâmetros clínico-bioquímicos, quando considerados isoladamente, não mostrou diferenças estatisticamente significantes entre os grupos I, II, e III, entretanto a classificação de Child/Campbell, discriminou o grupo infectado, onde houve predomínio da classe C, de pior prognóstico.

Understanding Human Carboxylesterase 2

Dissertation presented to obtain the Ph.D degree in Engineering and Technology Sciences, Biotechnology

HDL in HIV-1 infection: a quality perspective through paraoxonase-1 activities

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

Biodemes and zymodemes of Trypanosoma cruzi strains: correlations with clinical data and experimental pathology

With the objective of establishing biological and biochemical characteristics of a significant number of Trypanosoma cruzi strains from different geographical areas, 138 strains isolated from naturally infected humans, triatomine or vertebrate hosts were studied; 120 were isolated from different areas of Brazil and 18 from other South and Central American countries. Inocula from triatomine or culture forms were injected into suckling Swiss mice, followed by passages into mice 10 to 12 g. Biological characters and histopathological study permitted the inclusion of the strains into three Types or biodemes: I, II, III. Isoenzymic analysis confirmed a correspondence between the biodemes and zymodemes : Type I and Z2b, Type II and Z2, Type III and Z1. Results showed the ubiquitary distribution of the several types of strains. The predominance of the same Type and zymodeme in one geographical area was confirmed : Type II strains among the human cases from eastern Bahia and east of Goiás; Type III strains from humans of north Brazil and Central America and from silvatic vectors or vertebrates from other geographical areas. The biological types of strains correlate with different histopathological lesions considering cardiac involvement and neuronal lesions. These findings suggest that the biological behavior together with isoenzymes patterns and pathological pictures in the vertebrate host can be an important tool for establishing correlations between strains behavior and clinico-pathological manifestations of Chagas' disease in different geographical areas.

Detection of HTLV-IIa in blood donors in an urban area of the Amazon Region of Brazil (Belém, PA)

The human lymphotropic viruses type I (HTLV-I) and type II (HTLV-II) are members of a group of mammalian retroviruses with similar biological properties, and blood transfusion is an important route of transmission. HTLV-I is endemic in a number of different geographical areas and is associated with several clinical disorders. HTLV-II is endemic in several Indian groups of the Americas and intravenous drug abusers in North and South America, Europe and Southeast Asia. During the year of 1995, all blood donors tested positive to HTLV-I/II in the State Blood Bank (HEMOPA), were directed to a physician and to the Virus Laboratory at the Universidade Federal do Pará for counselling and laboratory diagnosis confirmation. Thirty-five sera were tested by an enzyme immune assay, and a Western blot that discriminates HTLV-I and HTLV-II infection. Two HTLV-II positive samples were submitted to PCR analysis of pX and env genomic region, and confirmed to be of subtype IIa. This is the first detection in Belém of the presence of HTLV-IIa infection among blood donors. This result emphasizes that HTLV-II is also present in urban areas of the Amazon region of Brazil and highlights the need to include screening tests that are capable to detect antibodies for both types of HTLV.

Formulação de Políticas Públicas no Horizonte 2013 relativas ao tema Acessibilidades e Transportes

FIGUEIRA DE SOUSA, J. e NUNES DA SILVA, F. (coord.); FONSECA; C.C.; CASTRO, H.; MARTINS, M.J.; SALVADOR, R.; CARVALHO, V.C.; GOMES, A..A.; FERNANDES, A.; MARQUES, B.P. e CONCHINHA, J.R. (2005) Formulação de Políticas Públicas no Horizonte 2013 relativas ao tema Acessibilidades e Transportes, IDE/e-GEO/CESUR para a DGDR, Lisboa.

Avaliação da eficácia terapêutica da ivermectina sobre larvas de quarto estádio de Lagochilascaris minor em gatos infectados experimentalmente

Avaliou-se a ação da ivermectina sobre larvas de quarto estádio em gatos infectados experimentalmente com Lagochilascaris minor. Foram utilizados 30 gatos (divididos, igualmente, em três grupos I, II e III), sendo que cada animal foi inoculado, por via oral, com 50 larvas de terceiro estádio do parasito. Cada animal, dos grupos I e II, foi tratado com ivermectina na dosagen de 200mig/kg, no quinto dia após o inóculo (DAI). Os animais do grupo I foram examinados, clinicamente, entre 30 e 40 dias e os do grupo II entre 180 e 190 dias sendo, em seguida, submetidos à necropsia. Os dez animais do grupo III, não foram tratados com a droga constituindo o grupo controle. Independentemente do período de observação, observou-se 100% de eficácia da droga, visto que houve total interrupção do ciclo biológico do parasito em todos animais tratados. Todos animais do grupo controle desenvolveram a infecção por Lagochilascaris minor.