Variability and resistance mutations in the hepatitis C virus NS3 protease in patients not treated with protease inhibitors

The goal of treatment of chronic hepatitis C is to achieve a sustained virological response, which is defined as exhibiting undetectable hepatitis C virus (HCV) RNA levels in serum following therapy for at least six months. However, the current treatment is only effective in 50% of patients infected with HCV genotype 1, the most prevalent genotype in Brazil. Inhibitors of the serine protease non-structural protein 3 (NS3) have therefore been developed to improve the responses of HCV-infected patients. However, the emergence of drug-resistant variants has been the major obstacle to therapeutic success. The goal of this study was to evaluate the presence of resistance mutations and genetic polymorphisms in the NS3 genomic region of HCV from 37 patients infected with HCV genotype 1 had not been treated with protease inhibitors. Plasma viral RNA was used to amplify and sequence the HCV NS3 gene. The results indicate that the catalytic triad is conserved. A large number of substitutions were observed in codons 153, 40 and 91; the resistant variants T54A, T54S, V55A, R155K and A156T were also detected. This study shows that resistance mutations and genetic polymorphisms are present in the NS3 region of HCV in patients who have not been treated with protease inhibitors, data that are important in determining the efficiency of this new class of drugs in Brazil.

Evaluación económica de la monoterapia con tocilizumab frente a adalimumab en artritis reumatoide.

BACKGROUND Tocilizumab (TCZ) was superior to adalimumab (ADA), as monotherapy, in reducing signs and symptoms of adult rheumatoid arthritis (RA) when methotrexate (MTX) treatment is poorly tolerated or inappropriate. The aim of the study was to analyze the cost-effectiveness of TCZ vs ADA in these patients. METHODS Economic evaluation of the cost per response or remission of TCZ vs ADA from ADACTA (time horizon: 24 weeks). Clinical response criteria ACR or disease remission criteria, DAS28. PERSPECTIVE National Health System. The costs included (acquisition, administration and monitoring of medicines; € 2012) were obtained from Spanish sources. Simple univariate sensitivity analyzes were performed. RESULTS ACR20, ACR50 and ACR70 response rates with TCZ and ADA were obtained in 65% and 49.4% (p <0.01), 47.2% and 27.8% (p <0.01); and 32.5% and 17.9% (p <0.01) of patients, respectively. DAS28 remission occurred in 39.9% and 10.5%, respectively (p <0.0001). The cost per response was lower with TCZ than with ADA (ACR20: € 8,105 and € 11,553; ACR50: € 11,162 and € 20,529; ACR70: € 16,211 and € 31,882) respectively. The cost of DAS28 remission was € 13,204 and € 54,352, respectively. Treatment with TCZ was dominant (more effective, with lower costs vs ADA) in all scenarios analyzed. CONCLUSIONS According to this analysis, in Spain TCZ monotherapy is an efficient strategy vs ADA for treating RA patients intolerant to MTX or in which there is inappropriate response.

Manejo de la violencia psicológica: una revisión bibliográfica

Publicado en la plataforma de la Red Sabia (Red de Salud y Buen Trato a la Infancia y la Adolescencia. http://www.redsabia.org/) de la Consejería de Igualdad, Salud y Políticas Sociales

Zika virus damages the human placental barrier and presents marked fetal neurotropism

An unusually high incidence of microcephaly in newborns has recently been observed in Brazil. There is a temporal association between the increase in cases of microcephaly and the Zika virus (ZIKV) epidemic. Viral RNA has been detected in amniotic fluid samples, placental tissues and newborn and fetal brain tissues. However, much remains to be determined concerning the association between ZIKV infection and fetal malformations. In this study, we provide evidence of the transplacental transmission of ZIKV through the detection of viral proteins and viral RNA in placental tissue samples from expectant mothers infected at different stages of gestation. We observed chronic placentitis (TORCH type) with viral protein detection by immunohistochemistry in Hofbauer cells and some histiocytes in the intervillous spaces. We also demonstrated the neurotropism of the virus via the detection of viral proteins in glial cells and in some endothelial cells and the observation of scattered foci of microcalcifications in the brain tissues. Lesions were mainly located in the white matter. ZIKV RNA was also detected in these tissues by real-time-polymerase chain reaction. We believe that these findings will contribute to the body of knowledge of the mechanisms of ZIKV transmission, interactions between the virus and host cells and viral tropism.

"Francisci Barbari liber de re uxoria" (3), avec des lettres de Pogge (2, 47v).

Acquis parmi 44 mss. provenant du cabinet du pape Pie VI (Giovanni-Angelo Braschi) "peu après l'envoi principal des mss. du Vatican en 1797"; cf. B.n.F., département des Manuscrits, Archives Modernes 492, registre des acquisitions du département des Manuscrits an II-an XIV (1793-1805), f. 49, description éditée par M.-P. Laffitte, Bulletin du Bibliophile, 1989/2, 310.

Le Panégyrique de Monseigneur le Duc de Beaufort Pair de France

[Mazarinade. 1649]

Le cavalier d'outre-mer

[Mazarinade. 1649]

L'achat de Mazarin, en vers burlesques.

[Mazarinade. 1649]

Realizar pesquisa sem ação ou pesquisa-ação na área de Administração? Uma reflexão metodológica

Neste artigo, o objetivo é analisar como a pesquisa-ação tem sido aplicada nos estudos da área de Administração no Brasil. Apresenta-se um recorte da pesquisa-ação nos estudos brasileiros em Administração, escrutinando trabalhos de 44 periódicos nacionais de Administração, e 38 encontros ou simpósios da Associação Nacional de Pós-Graduação e Pesquisa em Administração (Anpad), entre os anos de 2000 e 2010. Identificaram-se 22 artigos em periódicos e quatro em eventos da Anpad que referenciavam pesquisa-ação, porém, apenas 21 compuseram o estrato final de artigos examinados. Analisaram-se objetivos, procedimentos, nível de engajamento de outsiders e consequências do ciclo acadêmico e do ciclo da ação, tanto para a ciência quanto para a realidade sob intervenção. Nos resultados da pesquisa, indica-se que, no geral, os autores não distinguem apropriadamente as duas intenções da metodologia, salvo poucas exceções. Especula-se, então, sobre a utilização da pesquisa-ação no campo de estudo da administração no Brasil. Conclui-se que o conceito de pesquisa-ação é reconhecido e internalizado pelos autores, mas os relatos de sua aplicação ainda são deficientes. Por fim, argumenta-se que pesquisa e ação na área de Administração podem e devem caminhar juntas e propõem-se algumas sugestões de pesquisas.

Le bandeau de l'honneur. En vers burlesques.

[Mazarinade. 1649]

Soupirs françois redoublez, sur la paix italienne. Magna est veritas & prævalet !

[Mazarinade. 1649]

L'Agatonphile de la France

[Mazarinade. 1649]

Le portraict de l'inconstance des armes

[Mazarinade. 1649]