Endostatin- and interleukin-2-expressing retroviral bicistronic vector for gene therapy of metastatic renal cell carcinoma

Background Metastatic renal cell carcinoma (mRCC) is one of the most treatment-resistant malignancies. Despite all new therapeutic advances, almost all patients develop resistance to treatment and cure is rarely seen. In the present study, we evaluated the antitumor effect of a bicistronic retrovirus vector encoding both endostatin (ES) and interleukin (IL)-2 using an orthotopic metastatic RCC mouse model. Methods Balb/C-bearing Renca cells were treated with NIH/3T3-LendIRES-IL-2-SN cells. In the survival studies, mice were monitored daily until they died. At the end of the in vivo experiment, serum levels of IL-2 and ES were measured, the lung was weighed, and the number of metastatic nodules, nodule area, tumor vessels and proliferation of tumor-infiltrating Renca cells were determined. Results Inoculation of NIH/3T3-LendIRES-IL-2-SN cells resulted in an increase in ES and IL-2 levels in the treated group (p < 0.05). There was a significant decrease in lung wet weight, lung nodule area and tumor vessels in the treated group compared to the control group (p < 0.001). The proliferation of Renca cells in the bicistronic-treated group was significantly reduced compared to the control group (p < 0.05). Kaplan-Meier survival curves showed that the probability of survival was significantly higher for mice submitted to bicistronic therapy (log-rank test, p = 0.0016). Bicistronic therapy caused an increase in the infiltration of CD4, CD4 interferon (IFN)gamma-producing, CD8, CD8 IFN gamma-producing and natural killer (CD49b) cells. Conclusions Retroviral bicistronic gene transfer led to the secretion of functional ES and IL-2 that was sufficiently active to: (i) inhibit tumor angiogenesis and tumor cell proliferation and (ii) increase the infiltration of immune cells (C) Copyright. 2011 John Wiley & Sons, Ltd.

Endostatin gene therapy enhances the efficacy of IL-2 in suppressing metastatic renal cell carcinoma in mice

We investigated whether the administration of IL-2 combined with endostatin gene therapy was able to produce additive or even synergistic immunomodulatory activity in a mouse model of metastatic renal carcinoma. Renca cells were injected into the tail vein of BALB/c mice. After 24 h, the animals were randomly divided into four groups (5 mice/group). One group of mice was the control, the second group received treatment with 100,000 UI of Recombinant IL-2 (Proleukin, Chiron) twice a day, 1 day per week during 2 weeks (IL-2), the third group received treatment with a subcutaneous inoculation of 3.6 x 10(6) endostatin-producing cells, and the fourth group received both therapies (IL-2 + ES). Mice were treated for 2 weeks. In the survival studies, 10 mice/group daily, mice were monitored daily until they died. The presence of metastases led to a twofold increase in endostatin levels. Subcutaneous inoculation of NIH/3T3-LendSN cells resulted in a 2.75 and 2.78-fold increase in endostatin levels in the ES and IL-2 + ES group, respectively. At the end of the study, there was a significant decrease in lung wet weight, lung nodules area, and microvascular area (MVA) in all treated groups compared with the control group (P < 0.001). The significant difference in lung wet weight and lung nodules area between groups IL-2 and IL-2 + ES revealed a synergistic antitumor effect of the combined treatment (P < 0.05). The IL-2 + ES therapy Kaplan-Meier survival curves showed that the probability of survival was significantly higher for mice treated with the combined therapy (log-rank test, P = 0.0028). Conjugated therapy caused an increase in the infiltration of CD4, CD8 and CD49b lymphocytes. An increase in the amount of CD8 cells (P < 0.01) was observed when animals received both ES and IL-2, suggesting an additive effect of ES over IL-2 treatment. A synergistic effect of ES on the infiltration of CD4 (P < 0.001) and CD49b cells (P < 0.01) was also observed over the effect of IL-2. Here, we show that ES led to an increase in CD4 T helper cells as well as cytotoxic lymphocytes, such as NK cells and CD8 cells, within tumors of IL-2 treated mice. This means that ES plays a role in supporting the actions of T cells.

Auditory results from cochlear implants in elderly people

According to data from the Brazilian Institute of Geography and Statistics, the elderly population grew 47.8% in the last decade in Brazil. A portion of this population has severe and/or profound hearing loss and do not benefit from conventional hearing aids. Thus, the use of cochlear implant is required. Aim: To analyze the benefits of cochlear implants in the elderly based on the comparison of primary auditory thresholds before and after the operation, discrimination of sentences in speech and in talking on the telephone. Methodology: Retrospective cohort study, analyzing medical records from patients aged over 60 years, users of cochlear implant for at least 1 year. Results: Fourteen medical records were analyzed. Mean age of patients was 63.07 years. The mean pure tone thresholds between 500Hz, 1kHz, 2kHz and 4kHz before the implantation was 113dBHL. None of the patients, before operation, could discriminate sentences in open sets and only 3 scored 17% in closed sets sentence recognition. After one year of implantation, the mean sound field thresholds reached 34dBHL, and open set sentences recognition of 93.57%, while 71% of the patients had become able to have a conversation on the telephone. Conclusion: The elderly users of cochlear implant showed important outcomes, with significant improvement in understanding in the open set and in using the telephone.

Microangiopathy of the inner ear, deafness, and cochlear implantation in a patient with Susac syndrome

Conclusion: The cochlear implant was beneficial as an attempt to restore hearing and improve communication abilities in this patient with profound sensorineural hearing loss secondary to Susac syndrome. Objective: To report the audiological outcomes of cochlear implantation (CI) in a young woman with Susac syndrome after a 6-month follow-up period. Susac syndrome is a rare disorder. It is clinically characterized by a typical triad of sensorineural deafness, encephalopathy, and visual defect, due to microangiopathy involving the brain, inner ear, and retina. Methods: This was a retrospective review of a case at a tertiary referral center. After diagnosis, the patient was evaluated by a multidisciplinary team and received a cochlear implant in her right ear. Results: The patient achieved 100% open-set sentence recognition in noise conditions and 92% monosyllable and 68% medial consonant recognition in quiet conditions after 6 months of implant use. She reported the use of the telephone 3 months after activation.

Higher prevalence of obsessive-compulsive spectrum disorders in rheumatic fever

Objective: This study aims to compare the prevalence of obsessive-compulsive spectrum disorders (OCSD) in psychiatric outpatients with and without a history of rheumatic fever (RF). Methods: An analytical cross-sectional study assessing a large sample of consecutive psychiatric outpatients at a Brazilian private practice was conducted during a 10-year period. Psychiatric diagnoses were made by a senior psychiatrist based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Best-estimate diagnosis procedure was also performed. Results: The total sample comprised 678 subjects, 13 of whom (1.92%) presented with a previous history of RF. This group showed a higher prevalence of subclinical obsessive-compulsive disorder (P=.025) and OCSD (P=.007) when compared to individuals with no such history. Conclusions: A previous history of RF was associated with OCSD. These results suggest that clinicians should be encouraged to actively investigate obsessive-compulsive symptoms and related disorders in patients with a positive history of RF. (C) 2009 Published by Elsevier Inc.

Application of recombinant antibody library for screening specific antigens in a bovine sperm cell subpopulation

Antibody phage display libraries are a useful tool in proteomic analyses. This study evaluated an antibody recombinant library for identification of sex-specific proteins on the sperm cell surface. The Griffin.1 library was used to produce phage antibodies capable of recognizing membrane proteins from Nelore sperm cells. After producing soluble monoclonal scFv, clones were screened on Simental sperm cells by flow cytometry and those that bound to 40-60% of cells were selected. These clones were re-analyzed using Nelore sperm cells and all clones bound to 40-60% of cells. Positive clones were submitted to a binding assay against male and female bovine leukocytes by flow cytometry and one clone preferentially bound to male cells. The results indicate that phage display antibodies are an alternative method for identification of molecules markers on sperm cells. (C) 2007 Elsevier B.V. All rights reserved.

Volumes de substratos comerciais, solo e composto orgânico afetando a formação de mudas de maracujazeiro-amarelo em diferentes ambientes de cultivo

Este trabalho teve como objetivo avaliar o crescimento de mudas de maracujazeiro- amarelo em três diferentes tamanhos de recipientes, em três condições de cultivo protegido, utilizando seis diferentes substratos. Foram empregados três ambientes de cultivo: (A1) estufa em arco, coberta de filme de polietileno de 150 μm, abertura zenital e tela termorrefletora de 50% sob o filme; (A2) viveiro agrícola de tela de monofilamento, com 50% de sombra; e (A3) viveiro agrícola de tela termorrefletora, com 50% de sombra. Foram testados três volumes (V1 = xx cm³ -sacolas de polietileno de 7,5 x 11,5 cm; V2 = xx cm33 - sacolas de polietileno 10,0 x 16,5 cm; e V3 = xx cm33 -sacolas de polietileno de 15,0 x 21,5 cm) e seis substratos (S1 = solo; S2 = Plantmax®; S3 = vermiculita; S4 = fibra de coco; S5 = fibra de coco chips; e S6 = Organosuper®, composto orgânico comercial). O delineamento experimental foi inteiramente casualizado, em esquema de parcelas subsubdivididas, em que os ambientes foram as parcelas, os recipientes de diferentes volumes as subparcelas e os substratos as subsubparcelas. Aos 50 dias após a semeadura, foram medidos a altura das plantas, o comprimento da raiz, a massa de matéria seca da parte aérea e das raízes. A partir das massas de matéria seca determinaram-se a relação massa de matéria seca de parte aérea e raiz e massa de matéria seca total. A estufa foi o melhor ambiente quando se utilizou o recipiente de XX cm33 o qual proporcionou mudas maiores, com maior biomassa seca aérea, radicular e total. A vermiculita foi o melhor substrato, porém o solo adubado é uma alternativa menos dispendiosa para a região.

Perspectiva histórica em administração: novos objetos, novos problemas, novas abordagens

A pesquisa busca contribuir para uma melhor compreensão do pensamento administrativo por meio da análise da utilização da perspectiva histórica em administração. Embora a aproximação entre administração e história não seja recente, ainda não avançou substancialmente de forma a viabilizar seu potencial ontológico, epistemológico e metodológico. De forma a aprofundar essa discussão, classificamos três abordagens do pensar administrativo relacionando-as com a discussão paradigmática da história, quais sejam: a história dos negócios (business history); a história da gestão (management history); e a história organizacional (organizational history). Tal enquadramento permitiu identificar que a perspectiva histórica da nova história inserida numa posição reorientacionista possibilita: a) refletir sobre a práxis social do pesquisador; b) considerar novos objetos, problemas e abordagens de pesquisa; e c) perceber que novas perguntas podem deslocar o foco de análise do exógeno para o local, o que contribui para o desenvolvimento de análises mais críticas sobre ideologias administrativas.

Revisitando os Clássicos da RAP

Este artigo revisita uma investigação realizada pelo Programa de Estudos de Administração Brasileira (Abras) em 2002, sobre os Clássicos da Revista de Administração Pública (RAP). Originalmente divulgado no formato de CD-ROM, como parte dos eventos comemorativos dos 35 anos de publicação ininterrupta daquele periódico, o texto discorre sobre a metodologia daquela investigação e revela 10 trabalhos que podem ser considerados os clássicos da revista. O banco de dados gerado pela pesquisa analisou cerca de 4.500 artigos de 13 revistas acadêmicas, registrando 887 citações aos artigos publicados pela RAP (total: cerca de 1.440) ao longo dos primeiros 35 anos de sua existência.

Políticas públicas para as comunicações no Brasil: adequação tecnológica e liberdade de expressão

Pouco se tem debatido, no campo da pesquisa acadêmica em administração, as políticas públicas para as comunicações no Brasil. Este artigo analisa essas políticas de acordo com uma perspectiva histórica a partir de 1964 até o presente, utilizando como fonte trabalhos acadêmicos, não-acadêmicos e o manancial legal existente. Tem como focos, dentro do âmbito das comunicações, a radiodifusão e a mídia impressa. A análise foi feita com base em princípios e postulados tidos como essenciais: ao funcionamento do setor, como a independência da imprensa em relação ao Estado; a interesses privados e a participação que esse ator tem na formação da infra-estrutura necessária às comunicações. Assim, o debate se divide em duas dimensões originais: a tecnológica, referente à montagem da infra-estrutura existente; e a informacional, dependente da regulação da liberdade de expressão pelo Estado. As considerações finais apontam para o caráter questionável da independência da mídia brasileira; a vinculação entre atores e interesses públicos e privados; e a confusão proposital entre liberdade de imprensa e de empresa.

Operational modal monitoring of ancient structures using wireless technology

Operational Modal Analysis is currently applied in structural dynamic monitoring studies using conventional wired based sensors and data acquisition platforms. This approach, however, becomes inadequate in cases where the tests are performed in ancient structures with esthetic concerns or in others, where the use of wires greatly impacts the monitoring system cost and creates difficulties in the maintenance and deployment of data acquisition platforms. In these cases, the use of sensor platforms based on wireless and MEMS would clearly benefit these applications. This work presents a first attempt to apply this wireless technology to the structural monitoring of historical masonry constructions in the context of operational modal analysis. Commercial WSN platforms were used to study one laboratory specimen and one of the structural elements of a XV century building in Portugal. Results showed that in comparison to the conventional wired sensors, wireless platforms have poor performance in respect to the acceleration time series recorded and the detection of modal shapes. However, for frequency detection issues, reliable results were obtained, especially when random excitation was used as noise source.

A escola como estímulo ao consumo de bens culturais. Caso prático nas disciplinas de História e Geografia

Este relatório descreve a Prática de Ensino Supervisionada na Escola Secundária Miguel Torga (Monte Abraão), no ano letivo de 2012/2013, e na Escola Secundária Passos Manuel (Lisboa) durante o ano letivo de 2013/2014. A reflexão crítica centrar-se-á na observação de aulas e na prática letiva de vários níveis de ensino: em História – 7º e 10º anos; em Geografia – 10º e 11º anos de escolaridade. O relatório está dividido em duas partes. Na primeira, faz-se uma breve apresentação do tema central do trabalho – a escola como estímulo ao consumo de bens culturais – em que se justifica a escolha do tema e se analisam os resultados estatísticos obtidos a partir de um inquérito aplicado aos alunos das turmas a que lecionei, com o objetivo de diagnosticar os seus hábitos culturais e o modo como ocupam os tempos livres. Segue-se uma abordagem de conceitos relacionados com o tema – bens culturais, cultura de massas, cultura erudita e cultura alternativa – depois analisam-se as vantagens de um ensino que valoriza a educação cultural e, finalmente, discutem-se os possíveis entraves com que o professor se depara na implementação destas estratégias. Na segunda parte, descrevem-se algumas experiências de ensino-aprendizagem desenvolvidas durante a Prática de Ensino Supervisionada que tiveram por objetivo implementar estratégias valorizadoras dos conteúdos de temática cultural. Apresentam-se diversos materiais e recursos utilizados em sala de aula e justifica-se a respetiva escolha, nomeadamente no tocante à pertinência e adequação aos conteúdos do programa e à lógica destes no âmbito da formação cívica e intelectual dos estudantes. Finaliza-se o relatório com uma reflexão sobre a vivência do estagiário nas escolas.

An evolutionary multi-objective optimization system for earthworks

Earthworks involve the levelling or shaping of a target area through the moving or processing of the ground surface. Most construction projects require earthworks, which are heavily dependent on mechanical equipment (e.g., excavators, trucks and compactors). Often, earthworks are the most costly and time-consuming component of infrastructure constructions (e.g., road, railway and airports) and current pressure for higher productivity and safety highlights the need to optimize earthworks, which is a nontrivial task. Most previous attempts at tackling this problem focus on single-objective optimization of partial processes or aspects of earthworks, overlooking the advantages of a multi-objective and global optimization. This work describes a novel optimization system based on an evolutionary multi-objective approach, capable of globally optimizing several objectives simultaneously and dynamically. The proposed system views an earthwork construction as a production line, where the goal is to optimize resources under two crucial criteria (costs and duration) and focus the evolutionary search (non-dominated sorting genetic algorithm-II) on compaction allocation, using linear programming to distribute the remaining equipment (e.g., excavators). Several experiments were held using real-world data from a Portuguese construction site, showing that the proposed system is quite competitive when compared with current manual earthwork equipment allocation.

Prevalência de comportamentos alimentares disfuncionais em mulheres idosas

Dissertação de mestrado em Psicologia Aplicada (área de especialização em Psicologia Clínica e da Saúde)

Responsividade sensível da cuidadora e processamento de expressões faciais emocionais em crianças institucionalizadas: um estudo com potenciais evocados

Dissertação de mestrado em Psicologia Aplicada