A human immune data-informed vaccine concept elicits strong and broad T-cell specificities associated with HIV-1 control in mice and macaques

Background: None of the HIV T-cell vaccine candidates that have reached advanced clinical testing have been able to induce protective T cell immunity. A major reason for these failures may have been suboptimal T cell immunogen designs. Methods: To overcome this problem, we used a novel immunogen design approach that is based on functional T cell response data from more than 1,000 HIV-1 clade B and C infected individuals and which aims to direct the T cell response to the most vulnerable sites of HIV-1. Results: Our approach identified 16 regions in Gag, Pol, Vif and Nef that were relatively conserved and predominantly targeted by individuals with reduced viral loads. These regions formed the basis of the HIVACAT T-cell Immunogen (HTI) sequence which is 529 amino acids in length, includes more than 50 optimally defined CD4+ and CD8+ T-cell epitopes restricted by a wide range of HLA class I and II molecules and covers viral sites where mutations led to a dramatic reduction in viral replicative fitness. In both, C57BL/6 mice and Indian rhesus macaques immunized with an HTI-expressing DNA plasmid (DNA.HTI) induced broad and balanced T-cell responses to several segments within Gag, Pol, and Vif. DNA.HTI induced robust CD4+ and CD8+ T cell responses that were increased by a booster vaccination using modified virus Ankara (MVA.HTI), expanding the DNA.HTI induced response to up to 3.2% IFN-γ T-cells in macaques. HTI-specific T cells showed a central and effector memory phenotype with a significant fraction of the IFN-γ+ CD8+ T cells being Granzyme B+ and able to degranulate (CD107a+). Conclusions: These data demonstrate the immunogenicity of a novel HIV-1 T cell vaccine concept that induced broadly balanced responses to vulnerable sites of HIV-1 while avoiding the induction of responses to potential decoy targets that may divert effective T-cell responses towards variable and less protective viral determinants.

Síntese enzimática de butirato de isoamila empregando lipases microbianas comerciais

Isoamyl butyrate production was investigated using free and immobilized lipases by esterification of butyric acid with isoamyl alcohol in a solvent-free system and in an organic media. Among the enzymes studied, Lipozyme TL IM was found to be the most active catalyst in n-hexane as a solvent. The effects of different solvents and the amount of water added on conversion rates were studied. A maximum conversion yield of 80% in n-hexano at 48 h was obtained under the following conditions: 3 g L-1 of Lipozyme TL IM, 30 ºC, 180 rpm of agitation, isoamyl alcohol to butyric acid molar ratio of 1:1 and acid substrate concentration of 0.06 M.

Fitoquímica e quimiossistemática de Conchocarpus marginatus e C. inopinatus (Rutaceae)

Phytochemical studies of the leaves and stem have led to the identification of the known acridone alkaloids arborinine, methyl-arborinine, 1-hydroxy-3-methoxy-N-methyl acridone, xanthoxoline, 1,2,3,5-tetramethoxy-N-methylacridone, toddaliopsin C and the new seco acridone alkaloid inopinatin. The known quinoline alkaloids 2-phenyl-1-methyl-quinolin-4(1H)-one, 2-phenyl-1-methyl-7-methoxy-quinolin-4(1H)-one, dictamnine, and the coumarins scopoletin and marmesin were also isolated. The isolated compounds and the distribution of secondary metabolites, which are systematically important, obtained from literature, clearly confirmed that some species formerly described in the genera Angostura and Galipea in fact shall belong to the genus Conchocarpus.

Application of fourier transform infrared spectroscopy, chemical and chemometrics analyses to the characterization of agro-industrial waste

Agroindustrial waste in general presents significant levels of nutrients and organic matter and has therefore been frequently put to agricultural use. In this context, the objective of this study was to determine the chemical composition, nitrogen, phosphorus, potassium, calcium, magnesium and carbon content, as well as the qualitative characteristics through Fourier transform infrared spectroscopy of four samples of poultry litter and one sample of cattle manure, from the southwestern region of Paraná, Brazil. Results revealed that, in general, the poultry litter presented higher amount of nutrients and carbon than the cattle manure. The infrared spectra allowed identification of the functional groups present and the differences in degree of sample humification. The statistical treatment confirmed the quantitative and qualitative differences revealed.

Sukupuolittuneita teemoja keskiajalta

Kirjallisuusarvostelu

SISTEMAS ALTERNATIVOS DE CALIBRAÇÃO PARA DETERMINAÇÃO ESPECTROFOTOMÉTRICA SIMULTÂNEA DE ESPÉCIES COM INTERFERÊNCIA ESPECTRAL

Two simple and efficient procedures have been developed for the rapid simultaneous determination of compounds with mutual spectral interference (rifampicin (RIF) and isoniazid (INH)). The first method was based on the UV–Vis spectral signal (190–600 nm) of synthetic RIF and INH aqueous solutions, whereas the second method involved the visible spectral signal registered between 350 and 800 nm after the reaction of INH with a Cu2+/neocuproine complex. Both multivariate spectrophotometric methods show excellent prevision capacity, providing results that are statistically equivalent with those provided by the standard chromatographic procedure. The methods were validated according to criteria established by ANVISA, showing precision, accuracy and robustness compatible with the requirements for new analytical methods, additionally allowing the reduction of waste generation.

Magnetic, thermal and spectral properties of Ni(II) 2,3- , 3,5- and 2,6-dimethoxybenzoates

Complexes of Ni(II) 2,3-, 3,5- and 2,6-dimethoxybenzoates have been synthesized, their physico-chemical properties have been compared and the influence of the position of -OCH3 substituent on their properties investigated. The analysed compounds are crystalline, hydrated salts with green colour. The carboxylate ions show a bidentate chelating or bridging coordination modes. The thermal stabilities of Ni(II) dimethoxybenzoates were investigated in air in the range of 293-1173 K. The complexes decompose in three steps, yelding the NiO as the final product of decomposition. Their solubilities in water at 293 K are in the order of 10-2-10-4 mol×dm-3. The magnetic susceptibilities for the analysed dimethoxybenzoates of Ni(II) were measured over the range of 76-303 K and the magnetic moments were calculated. The results reveal that the complexes are the high-spin ones and the ligands form the weak electrostatic field in the octahedral coordination sphere of the central Ni(II) ion. The various position -OCH3 groups in benzene ring cause the different steric, mesomeric and inductive effects on the electron density in benzene ring.

Implantação das Diretrizes Curriculares Nacionais na graduação em Medicina no Paraná

A aprovação da nova LDB, em 1996, levou à elaboração de Diretrizes Curriculares Nacionais (DCN) baseadas em competências necessárias para os médicos atuarem frente às novas tecnologias e para enfrentarem os desafios do desenvolvimento do SUS. Analisar a implantação das DCN no Paraná, verificando as características da formação dos profissionais de Medicina, foi o objetivo desta publicação específica, que faz parte dos dados coletados numa pesquisa mais ampla, apoiada pelo edital universal do CNPq (Proc. 474.029/2003-04). O estudo foi realizado com uma abordagem qualitativa e análise de conteúdo. Fez-se um levantamento das Instituições de Ensino Superior (IES) que oferecem cursos de Medicina, coletando-se os dados por questionário e pelas informações dos Projetos Político-Pedagógicos (PPP) obtidos, com instrumento baseado em sete eixos das DCN. Dois cursos apresentam grau avançado de implantação das DCN, um mostra iniciativa da implantação de alguns aspectos, e dois outros seguem formatos curriculares bem tradicionais. Os dados obtidos sugerem a existência de uma motivação para a inovação do ensino médico no Paraná, o que se traduz em currículos idealizados com vários princípios inspirados nas DCN.

O uso de portfólio na prática de atendimento domiciliar a idosos no curso de Medicina

Este trabalho apresenta e analisa a utilização do portfólio na prática de atendimento domiciliar a idosos no Módulo do Envelhecimento do segundo ano do curso de Medicina da Universidade Estadual de Londrina. As informações analisadas foram obtidas dos 40 portfólios apresentados pelos alunos na conclusão do módulo em 2006. O portfólio é estruturado com dados de identificação, anamnese, exame físico, medicamentos, exames complementares e avaliações funcionais, cognitivas e sociais. As seguintes informações foram selecionadas para análise: descrição das visitas domiciliares e avaliação individual dos alunos. As principais vantagens identificadas pelos alunos foram à possibilidade de aplicação do conhecimento adquirido (50,0%), a criação de vínculos (37,2%) e o desenvolvimento da relação médico-paciente (35,9%). Como principais dificuldades, apontaram insegurança (26,9%), dúvida em relação ao consentimento (15,4%) e invasão de privacidade (12,8%). A análise sugere que a prática de atendimento domiciliar a idosos é importante para a formação de profissionais com condições de atender à população idosa. Além disso, o portfólio mostrou ser um recurso pedagógico que proporciona um aprendizado ativo e garante o envolvimento do aluno com o conteúdo proposto para a atividade.

Comunicação no ensino médico: estruturação, experiência e desafios em novos currículos médicos

Este artigo relata a experiência de um grupo de docentes do curso de Medicina da Universidade Estadual de Londrina no ensino de comunicação no módulo de Habilidades do currículo integrado. A constatação da importância da comunicação no relacionamento médico-paciente e na evolução de doenças levou à elaboração de uma estrutura com dificuldades progressivas ao longo dos quatro primeiros anos do curso. Os conteúdos abordados variam desde a observação de pacientes em sala de espera até a discussão técnica sobre a abordagem da transmissão de informações, adesão ao tratamento e manejo de grupos especiais de pacientes em diferentes fases da vida. As estratégias utilizadas incluem observação de pacientes, entrevistas, discussões em grupo, dramatizações, filmes, mesas-redondas, conferências e depoimentos de pacientes. A avaliação é feita em duas partes, formativa e cognitiva. O treinamento da comunicação visa desenvolver a competência do aluno em aprimorar seu vínculo com o paciente, potencializar os processos de obtenção e transmissão de informações, o manejo do paciente e a promoção da adesão ao tratamento.

Factors associated with depressive symptoms in a sample of Brazilian medical students

OBJECTIVES: 1 - Verify the prevalence of depressive symptoms in first to fourth-year medical students using the Beck Depression Inventory (BDI). 2 - Establish correlations between target factors and higher or lower BDI scores. 3 - Investigate the relationship between the prevalence of depressive symptoms and the demand for psychological care offered by the Centro Universitário Lusíada. METHOD: Cross-sectional study of 290 first to fourth-year medical students; implementation of the BDI, socio-demographic survey, and evaluation of satisfaction with progress. RESULTS: The study sample was 59% female and 41% male. Mean BDI was 6.3 (SD 5.8). Overall prevalence of depressive symptoms was 23.1%. The following associations were statistically significant (p<0.05): among students for whom the course failed to meet original expectations, who were dissatisfied with the course, or who came from the interior of the State (20.5%, 12.5%, and 24.4% of the total sample, respectively), for 40%, 36.1% and 36.4%, respectively, the BDI was consistent with some degree of depression. CONCLUSION: The study showed that there is higher prevalence of depressive symptoms in medical students than in the general population