Mechanisms of relapse in rheumatoid arthritis following B-lymphocyte depletion

An open label trial of B-lymphocyte depletion therapy (BLDT) based on rituximab in 5 patients with rheumatoid arthritis, initiated in 1998, had shown that this therapy was associated with major clinical improvement. B-lymphocyte repopulation had occurred before relapse in all patients and, interestingly, it had not been always associated with relapse. This thesis starts with an extension of the initial open label trial to 22 patients with results suggesting a dose response to rituximab. Further follow up of these and an additional 18 patients revealed that, although all patients eventually relapsed, as in the previous small study, relapse could occur either at the time of B-lymphocyte repopulation of the peripheral blood or at a variable time after this time point, up to almost 3 years. Re-treatment with BLDT was found to be well tolerated and effective. Upon re-treatment, patients usually repeated the same pattern of relapse. Disease-associated autoantibodies, rheumatoid factor of immunoglobulin A, G and M classes and antibodies to cyclic citrullinated peptides, fell in all patients following BLDT but only decreased significantly in those who responded to treatment. Comparison with changes observed in total immunoglobulin levels and anti-microbial antibodies, suggested a specific effect on autoantibodies. Relapse was almost always preceded or associated with a rise in autoantibody levels, particularly rheumatoid factor of immunoglobulin M isotype, and was more closely associated with a rise in autoantibody levels than with the presence of B lymphocytes per se. B-lymphocyte stimulator (BLyS) serum levels increased following BLDT. Levels decreased following B-lymphocyte repopulation but tended to be lower at the time of repopulation in the group of patients who relapsed at this time point. Immunophenotyping of peripheral blood B lymphocytes showed that depletion was major but not complete and that it involved all B-lymphocyte subpopulations. It suggested that a quantitative threshold of depletion needed to be reached for patients to respond to therapy. B-lymphocyte repopulation occurred mainly from naive cells with immature B lymphocytes present in increased numbers and frequency. Patients who relapsed at the time of B-lymphocyte repopulation tended to show increased frequency and increased numbers of circulating memory B lymphocytes at the time of repopulation. Immunophenotyping studies of bone marrow aspirates in 6 patients, 3 months after treatment with BLDT, showed that the frequency of cells of B-lymphocyte lineage at this time point varied between patients. The variable relationships between the frequencies of more immature and more mature B-lymphocyte precursors in the samples suggested different degrees of depletion. Samples from patients who relapsed the earliest showed a pattern suggesting less efficient depletion. In conclusion, the results presented here suggest that relapse following BLDT in patients with rheumatoid arthritis can be attributed to incomplete depletion of pathogenic B-lymphocyte clones, persistence of long-lived plasma cells producing pathogenic autoantibodies or to a combination of both. This will contribute to hypothesis-based development of B-lymphocyte targeting therapies

Influence Of Coarse Aggregate On Concrete's Elasticity Modulus

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)The modulus of elasticity of concrete is an important property because it is crucial for the control of deformation. The impossibility of obtaining concrete with higher elasticity modulus rates may cause economic liabilities due to the need for larger structural elements. Current paper evaluates three compressive strength classes (20, 30 and 40MPa) of concrete produced with two types of coarse aggregate, basalt and dolomite rock from the Triangulo Mineiro region, Brazil. Further, 459 cylindrical test specimens were cast for the experimental study. The experimental results of the elasticity modulus rates were compared and with formulations prescribed by four standards: ABNT NBR 6118, ACI 318, Eurocode 2 and FIB Model Code. Comparisons demonstrated that the effect of coarse aggregate on the elasticity modulus was negligible when compared to the concrete's resistance class.3911725CAPES (Federal Agency for the Support and Updating of Higher Education)FAPEMIG (Research Foundation of the State of Minas Gerais)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Integration of resources for access to Multimodal Learning Objects

Considerando os diferentes meios de acesso aos conteúdos educacionais tais como computador, mídia impressa, dispositivos móveis, etc. e as limitações de cada meio, deve-se atentar para a elaboração de conteúdos que possam ser acessados por diferentes meios, independente de local ou situação. Este artigo analisa algumas possibilidades de acesso a Objetos de Aprendizagem, bem como as preferências dos alunos em relação aos meios utilizados para estudo. Nesse contexto, o artigo apresenta uma proposta de OA e alguns resultados referentes à utilização do OA proposto.Considering the different means of access to educational content such as computer, print media, mobile devices, etc., and limitations of each means, should to attention to the development of content that can be accessed by different means, regardless of location or situation. This article examines some possibilities of access to learning objects, as well as the preferences of students in relation to the means employed to study. In this context, the paper presents a proposal for LO and some results concerning the use of LO

Positive selection evidence in xylose-related genes suggests methylglyoxal reductase as a target for the improvement of yeasts' fermentation in industry

Xylose assimilation and fermentation are important traits for second generation ethanol production. However, some genomic features associated with this pentose sugar's metabolism remain unknown in yeasts. Comparative genomics studies have led to important insights in this field, but we are still far from completely understanding endogenous yeasts' xylose metabolism. In this work, we carried out a deep evolutionary analysis suited for comparative genomics of xylose-consuming yeasts, searching for of positive selection on genes associated with glucose and xylose metabolism in the xylose-fermenters' clade. Our investigation detected positive selection fingerprints at this clade not only among sequences of important genes for xylose metabolism, such as xylose reductase and xylitol dehydrogenase, but also in genes expected to undergo neutral evolution, such as the glycolytic gene phosphoglycerate mutase. In addition, we present expansion, positive selection marks, and convergence as evidence supporting the hypothesis that natural selection is shaping the evolution of the little studied methylglyoxal reductases. We propose a metabolic model suggesting that selected codons among these proteins caused a putative change in cofactor preference from NADPH to NADH that alleviates cellular redox imbalance. These findings provide a wider look into pentose metabolism of yeasts and add this previously overlooked piece into the intricate puzzle of oxidative imbalance. Although being extensively discussed in evolutionary works the awareness of selection patterns is recent in biotechnology researches, rendering insights to surpass the reached status quo in many of its subareas11719231938COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPnão tem2013/08293-7; 2015/05578-6; 2017/07008-8; 2017/08519-

GESTÃO FINANCEIRA: UM ESTUDO COM OS SERVIDORES PÚBLICOS DA PREFEITURA DE TANGARÁ DA SERRA - MT

The objective of the research was to identify the financial management perception of public servants in the city of Tangará da Serra - MT. This is a descriptive study, with a quantitative approach, using the case study as a method, the sample comprised 162 civil servants who work directly in the city hall building. The data collection instrument was a structured questionnaire, segregated into three blocks: block I - addresses the socioeconomic profile; block II - seeks to identify how financial management is carried out and; block III - aims to get to know personal perception in relation to the good financial manager. The data were organized using Microsoft Office Excel software and presented in tables and graphs. For the open questions, the WordArt tool was used to elaborate the “Word Cloud”. Regarding the socioeconomic profile of civil servants, most are female, aged between 36 and 45 years and complete higher education, have a family net monthly income of up to 5 minimum wages and work for more than 10 years in the public service. Regarding the management of resources, the majority revealed to have good financial attitudes, although in some aspects they presented negative results. The male gender demonstrated greater mastery in financial management.O objetivo da pesquisa foi identificar a percepção de gestão financeira dos servidores públicos da prefeitura de Tangará da Serra – MT. Trata-se de um estudo descritivo, com abordagem quantitativa, utilizou como método o estudo de caso, a amostra compreendeu 162 servidores que trabalham diretamente no prédio da prefeitura municipal. O instrumento de coleta de dados foi questionário estruturado, segregado em três blocos: bloco I – aborda o perfil socioeconômico; bloco II – busca identificar como é realizada a gestão financeira e; bloco III - visa conhecer percepção pessoal em relação ao bom gestor financeiro. Os dados foram organizados com uso software Microsoft Office Excel e apresentados em tabelas e gráficos, para as questões abertas utilizou a ferramenta WordArt para elaborar a “Nuvem de Palavras”. Quanto ao perfil socioeconômico dos servidores públicos a maioria é do gênero feminino, com faixa etária entre 36 a 45 anos e nível superior completo, possuem renda mensal líquida familiar de até 5 salários mínimos e atuam a mais de 10 anos no serviço público. Referente a gestão dos recursos, a maioria revelou ter boas atitudes financeiras, apesar de em alguns quesitos apresentarem resultados negativos. O gênero masculino demonstrou maior domínio em gestão financeira

COMERCIALIZAÇÃO DE PRODUTOS AGRÍCOLAS ORGÂNICOS COMO FATOR DE INCLUSÃO SOCIAL E ECONÔMICA

Este artigo analisa o processo de implantação da agricultura orgânica em assentamentos de reforma agrária, ainda recente no Brasil, e que trouxe consigo uma rápida transformação para a agricultura familiar. Procura analisar a contribuição da agricultura orgânica como alternativa de sustentabilidade sócio- econômica e ambiental da produção e entender o processo de reforma agrária brasileira e suas dificuldades, mostrando os possíveis caminhos para o agricultor assentado agregar valor à produção e se inserir em uma economia de mercado. Além do que, analisa os impactos identificados na elevação da renda familiar e melhoria nas condições de vida. Procurou-se analisar o caso do assentamento Ronda/Chico Mendes, no município de Pombos, em Pernambuco. A pesquisa constou de entrevistas e aplicação de questionários aos assentados, que levantou informações sobre a produção do assentamento e outros aspectos relevantes, a exemplo da implementação da produção orgânica e conseqüente comercialização desses produtos. Observou-se que quase a metade dos assentados vivia com menos de R$200,00 por mês, e hoje com as feiras orgânicas apenas 5$200,00. O maior acréscimo observado foi no percentual de assentados que possuía uma renda de R$300,00 a menos de R$400,00. 19% dos agricultores entrevistados passaram a ter uma renda de mais de R$500,00 por mês, o que não acontecia nem antes nem depois da criação do assentamento. Os agricultores que possuem uma renda superior a 1 salário mínimo representam 81$200,00 for month, and today with organic fairs only 5% lives with an income below to R$200,00. The biggest observed addition was in the percentage of farmers that earned an income of R$300,00 to less of R$400,00. 19$500,00 for month, what it did not happen neither at that time nor afterwards of the creation of the nesting. The small farmers who possess a superior income the 1 minimum wage represent 81%. In the study of presented case we could verify how much organic agriculture in the nesting is promising, in terms of its contribution for setting of the man to the field and the generation of income for the small farmers of agrarian reform.Pequena agricultura familiar, reforma agrária, assentamentos e agricultura orgânica, small agriculture, agrarian reform, nesting, organic agriculture, Farm Management,

Anomalias da inervação do trato digestório de fetos de ratas expostas à etilenotioureia

PURPOSE: The pathophysiology of abnormalities associated with myenteric plexus lesions remains imperfectly understood. Such abnormalities have been correlated with subocclusive intestinal conditions in children with Hirschsprung's disease, cases of chronic constipation and, postoperatively, in cases of anorectal anomalies. This study evaluated abnormalities of the myenteric plexus in fetus from female rats that received ethylenethiourea. METHODS: Female rats were exposed to ethylenethiourea on the 11th day of pregnancy (experimental group) or to 0.9% physiological solution (control group). Abnormalities were only found in the experimental group. The digestive tract muscle layer was analyzed morphometrically and changes to the frequencies of nerve plexus cells and interstitial cells of Cajal were evaluated, using hematoxylin-eosin, S-100 protein, neuron-specific enolase and C-Kit, respectively. RESULTS: Muscle and skeletal abnormalities were observed in 100%, anorectal anomalies in 86%, absent tail in 71%, short tail in 29%, duodenal atresia in 5%, esophageal atresia in 5% and persistent omphalomesenteric duct in 5%. Histopathological analysis showed a thinner muscle layer associated with lower frequencies of ganglion cells and interstitial cells of Cajal, in all gastrointestinal tract. CONCLUSION: Severe nerve plexus abnormalities associated with muscle layer atrophy were observed throughout the gastrointestinal tract in newborn rats exposed to ethylenethiourea.OBJETIVO: As anomalias associadas a lesões dos plexos mioentéricos permanecem sem plena compreensão da sua fisiopatologia. Alterações nos plexos nervosos têm sido correlacionadas com quadros suboclusivos intestinais em crianças portadoras de doença de Hirschsprung, em constipação crônica e no pós-operatório de anomalias anorretais. Este estudo avaliou as anomalias do plexo mioentérico em fetos de ratos fêmea que ingeriram etilenotioureia (ETU). MÉTODOS: Ratos fêmea foram expostos no 11º dia de gestação a ETU 1% no Grupo Experimento e a solução fisiológica 0,9% no Grupo Controle. Foram observadas anomalias apenas no Grupo experimento, sendo realizada morfometria da camada muscular e avaliadas alterações da frequência celular nos gânglios do plexo mioentérico e nas células intersticiais de Cajal (CIC) utilizando hematoxilina-eosina, P S-100, Enolase Neurônio Específica e C-KIT. RESULTADOS: Foram observadas anomalias musculoesqueléticas (100%), anorretais (86%), ausência de cauda (71%), cauda curta (29%), atresia duodenal (5%), atresia esofágica (5%) e conduto onfalomesentérico persistente (5%). A análise histopatológica mostrou adelgaçamento da camada muscular associada às alterações da frequência das células ganglionares e das CIC em todos os segmentos do trato gastrointestinal. CONCLUSÃO: Foram observadas alterações graves nos plexos nervosos associadas ao adelgaçamento da camada muscular de todo o trato gastrointestinal nos fetos expostos a ETU.UNIVASFUniversidade Federal de São Paulo (UNIFESP) Department of Surgery Pediatric Surgery DivisionFederal Rural University Department of Veterinary MedicineFederal Rural University Department of Animal Morphology and PhysiologyUNIFESP, Department of Surgery Pediatric Surgery DivisionSciEL

Experiência de 20 anos em adrenalectomia videolaparoscópica

Introdução: As operações na glândula adrenal são realizadas para determinados cânceres, todas as massas biologicamente ativas, metástases, massas com mais de 4-5 cm encontradas incidentalmente e hiperplasia adrenal primária. Métodos: Estudo transversal e descritivo. Foram analisados os prontuários dos pacientes submetidos a adrenalectomia videolaparoscópica entre agosto de 1994 e novembro de 2014. Resultados: Foram realizadas 146 adrenalectomias videolaparoscópicas. Em 134 casos, foi realizada com sucesso, mas em 12 casos (8,2%), o procedimento foi convertido. Foram 97 pacientes do sexo feminino e 49 do sexo masculino, com idade variando de 9 a 81 anos (média de 46,7 anos). Foram removidas 56 adrenais direitas, 75 esquerdas e 15 bilaterais. O tamanho médio das adrenais foi de 5,7 cm, variando de 0,9 a 15 cm. A mediana do tempo de internação hospitalar pós-operatória foi de 4,5 dias. A mediana do tempo de cirurgia foi de 144 minutos. Houve complicações em 22,5% dos casos (maiores – casos em que houve conversão para cirurgia aberta, necessidade de reinternação hospitalar e óbito– e menores), sendo 10,9% complicações intraoperatórias e 11,6% pós-operatórias. Apenas sete (4,7%) pacientes foram considerados complicações maiores. Conclusão: A cirurgia realizada em nosso serviço está de acordo com o descrito na literatura, com taxas aceitáveis de complicações, com motivos de conversão compatíveis e com as indicações totalmente aceitáveis e condizentes. A adrenalectomia videolaparoscópica é a cirurgia de escolha para patologias cirúrgicas da glândula adrenal, exceto em casos de carcinoma adrenal localmente invasivo com comprometimento de outras estruturas.Introduction: Adrenal gland surgery is performed for some types of cancer, all biologically active masses, metastases, masses larger than 4-5 cm found incidentally, and primary adrenal hyperplasia. Methods: A cross-sectional, descriptive study. Medical records of patients who underwent laparoscopic adrenalectomy from August 1994 to November 2014 were analyzed. Results: A total of 146 laparoscopic adrenalectomies were performed. In 134 cases, laparoscopic adrenalectomy was successfully performed, but in 12 cases (8.2%), the procedure was converted. There were 97 female patients and 49 male patients. Fifty-six right adrenal glands and 75 left adrenal glands were removed, and 15 patients had both of them removed. The average size of adrenal glands was 5.7 cm, ranging from 0.9 to 1.5 cm. The median length of postoperative hospital stay was 4.5 days, ranging from 1 to 55 days. The median surgery time was 144 minutes. There were 22.5% of complications (major ones – cases that required conversion to open surgery, hospital readmission, and death – and minor ones), of which 10.9% were intraoperative and 11.6% were postoperative. Only seven (4.7%) patients were classified as having major complications. Conclusion: The surgery performed in our department is consistent with the literature, showing acceptable rates of complications, compatible reasons for conversion, and completely acceptable and consistent indications. Laparoscopic adrenalectomy is the surgery of choice for diseases of the adrenal gland, except for locally invasive adrenal carcinoma compromising other structures

Densification and mechanical properties of sintered Al2 O3 -Y3 Al5 O12 ceramic composite

In this work, Al2 O3 -Y3 Al5 O12 ceramic composites were developed with different proportions of Al2 O3 -Y2 O3 , which were mixed and compacted at different pressures of 40MPa to 100MPa, being consequently sintered at 1600º C-2h. The sintered samples were characterized by X-ray diffraction presenting α−Al2 O3 and Y3 Al5 O12 as crystalline phases. Samples with relative densities ranging from 78 to 80% and 87 to 91% were obtained depending on the composition and the compaction pressure used. The hardness values obtained were of 1010 to 1080HV and 370- 470HV, for mixes Al2 O3 -Y2 O3 having the composition with levels of 20 and 36.5wt.%, respectively

Erythrina velutina Willd. alkaloids : piecing biosynthesis together from transcriptome analysis and metabolite profiling of seeds and leaves

Introduction: Natural products of pharmaceutical interest often do not reach the drug market due to the associated low yields and difficult extraction. Knowledge of biosynthetic pathways is a key element in the development of biotechnological strategies for plant specialized metabolite production. Erythrina species are mainly used as central nervous system depressants in folk medicine and are important sources of bioactive tetracyclic benzylisoquinoline alkaloids (BIAs), which can act on several pathology-related biological targets. Objectives: In this sense, in an unprecedented approach used with a non-model Fabaceae species grown in its unique arid natural habitat, a combined transcriptome and metabolome analyses (seeds and leaves) is presented. Methods: The Next Generation Sequencing-based transcriptome (de novo RNA sequencing) was carried out in a NextSeq 500 platform. Regarding metabolite profiling, the High-resolution Liquid Chromatography was coupled to DAD and a micrOTOF-QII mass spectrometer by using electrospray ionization (ESI) and Time of Flight (TOF) analyzer. The tandem MS/MS data were processed and analyzed through Molecular Networking approach. Results: This detailed macro and micromolecular approach applied to seeds and leaves of E. velutina revealed 42 alkaloids, several of them unique. Based on the combined evidence, 24 gene candidates were put together in a putative pathway leading to the singular alkaloid diversity of this species. Conclusion: Overall, these results could contribute by indicating potential biotechnological targets formodulation of erythrina alkaloids biosynthesis as well as improve molecular databases with omic data from a non-model medicinal plant, and reveal an interesting chemical diversity of Erythrina BIA harvested in Caatinga