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Algunos estudios han reportado un aumento en la frecuencia e importancia de las interacciones del itraconazol en pacientes bajo polifarmacia con fármacos que afectan el sistema enzimático de la citocromo P450 y modifican el metabolismo del azol. Con el propósito de determinar las características epidemiológicas, farmacológicas y clínicas de las interacciones medicamentosas en pacientes bajo tratamiento con itraconazol para diferentes tipos de micosis, se realizó un estudio descriptivo transversal retrospectivo en el que se analizaron 21 historias clínicas de pacientes atendidos en la Corporación para Investigaciones Biológicas durante el período 1994-1997. Entre la población estudiada, seis pacientes presentaron paracoccidioidomicosis; cinco, cromoblastomicosis; cuatro, histoplasmosis; cuatro, criptococosis, y dos, aspergilosis. En promedio, la dosis de itraconazol, la duración y el número de fármacos recibidos concomitantes fueron 223,8 mgldia, 44,3 semanas y 2,7 fármacos, respectivamente. En 10 individuos, se presentaron enfermedades de base y en 15, enfermedades concomitantes. Se documentó interacción medicamentosa (niveles no detectables o no terapéuticos de itraconazol) en 18 pacientes, de los cuales 17 presentaban sospecha clínica y 14 sospecha paraclínica de interacción. El medicamento más frecuentemente involucrado con interacción fue la rifampicina, seguido de los inhibidores H, antiácidos y fenitoina. Similar a lo encontrado en otros estudios, la administración concomitante de estos fármacos con el itraconazol, reduce los niveles séricos de este último y altera la respuesta clínica al tratamiento. Este estudio es una aproximación inicial, aún no realizada en nuestra población, que permitirá establecer protocolos para el manejo y prevención de interacciones medicamentosas en pacientes en tratamiento con itraconazol y otros fármacos.

Previous BAC clone analysis of the Platyrrhini owl monkey KIRs have shown an unusual genetic structure in some loci. Therefore, cDNAs encoding KIR molecules from eleven Aotus vociferans monkeys were characterized here; ten putative KIR loci were found, some of which encoded atypical proteins such as KIR4DL and transcripts predicted to encode a D0+D1 configuration (AOTVOKIR2DL1*01v1) which appear to be unique in the Aotus genus. Furthermore, alternative splicing was found as a likely mechanism for producing activator receptors in A. vociferans species. KIR proteins from New World monkeys may be split into three new lineages according to domain by domain phylogenetic analysis. Although the A. vociferans KIR family displayed a high divergence among paralogous genes, individual loci were limited in their genetic polymorphism. Selection analysis showed that both constrained and rapid evolution may operate within the AvKIR family. The frequent alternative splicing (as a likely mechanism generating activator receptors), the presence of KIR4DL and KIR2DL1 (D0+D1) molecules and other data reported here suggest that the KIR family in Aotus has had a rapid evolution, independent from its Catarrhini counterparts.

En el desarrollo de este artículo se realiza un análisis de los diferentes regímenes y elementos de responsabilidad que le son aplicables a las situaciones en las que se presenta un traslado tardío de los pacientes por parte de las E.S.E. Adicionalmente, se profundiza en la normatividad y jurisprudencia sobre el tema, lo cual se complementa con informes en investigaciones alternas sobre los protocolos de traslado de pacientes; todo esto con el fin de aportar una herramienta más de estudio para quienes se interesen sobre esta problemática.

A completely effective vaccine for malaria (one of the major infectious diseases worldwide) is not yet available; different membrane proteins involved in parasite-host interactions have been proposed as candidates for designing it. It has been found that proteins encoded by the merozoite surface protein (msp)-7 multigene family are antibody targets in natural infection; the nucleotide diversity of three Pvmsp-7 genes was thus analyzed in a Colombian parasite population. By contrast with P. falciparum msp-7 loci and ancestral P. vivax msp-7 genes, specie-specific duplicates of the latter specie display high genetic variability, generated by single nucleotide polymorphisms, repeat regions, and recombination. At least three major allele types are present in Pvmsp-7C, Pvmsp-7H and Pvmsp-7I and positive selection seems to be operating on the central region of these msp-7 genes. Although this region has high genetic polymorphism, the C-terminus (Pfam domain ID: PF12948) is conserved and could be an important candidate when designing a subunit-based antimalarial vaccine.

In the first few hours following Newcastle disease viral infection of human monocyte-derived dendritic cells, the induction of IFNB1 is extremely low and the secreted type I interferon response is below the limits of ELISA assay. However, many interferon-induced genes are activated at this time, for example DDX58 (RIGI), which in response to viral RNA induces IFNB1. We investigated whether the early induction of IFNBI in only a small percentage of infected cells leads to low level IFN secretion that then induces IFN-responsive genes in all cells. We developed an agent-based mathematical model to explore the IFNBI and DDX58 temporal dynamics. Simulations showed that a small number of early responder cells provide a mechanism for efficient and controlled activation of the DDX58-IFNBI positive feedback loop. The model predicted distributions of single cell responses that were confirmed by single cell mRNA measurements. The results suggest that large cell-to-cell variation plays an important role in the early innate immune response, and that the variability is essential for the efficient activation of the IFNB1 based feedback loop.

T-cell receptor gene rearrangements were studied in Aotus monkeys developing high antibody titers and sterilizing immunity against the Plasmodium falciparum malaria parasite upon vaccination with the modified synthetic peptide 24112, which was identified in the Merozoite Surface Protein 2 (MSP-2) and is known to bind to HLA-DRbeta1*0403 molecules with high capacity. Spectratyping analysis showed a preferential usage of Vbeta12 and Vbeta6 TCR gene families in 67% of HLA-DRbeta1*0403-like genotyped monkeys. Docking of peptide 24112 into the HLA-DRbeta1*0401-HA peptide-HA1.7TCR complex containing the VDJ rearrangements identified in fully protected monkeys showed a different structural signature compared to nonprotected monkeys. These striking results show the exquisite specificity of the TCR/pMHCII complex formation needed for inducing sterilizing immunity and provide important hints for a logical and rational methodology to develop multiepitopic, minimal subunit-based synthetic vaccines against infectious diseases, among them malaria.

Los métodos de rutina utilizados en el laboratorio para detectare identificar micobacterias en muestras clínicas de pacientes consintomatología sospechosa pueden tardar varias semanas, ya que son complejos y requieren un crecimiento adecuado en cultivo para ser completados. Actualmente se buscan métodos alternativos que permitan diagnosticar infecciones causadas por micobacterias de una manera más rápida y confiable, debido al incremento en la aparición de enfermedades causadas por estos microorganismos y a la diferencia en el tratamiento efectivo para cada una de ellas. Este estudio busca evaluar el método molecular descrito por Telenti (1), para identificar especies de micobacterias, aplicando una reacción en cadena de polimerasa (PCR) y digestión con enzimas de restricción.

La edad moderna ha traído consigo el confort, los computadores, las tarjetas de crédito, los avances científicos, las telecomunicaciones, la rapidez, la velocidad de la información, la facilidad de las cosas a corto plazo, el ya, el momento y el ahora.

El presente articulo da cuenta del trabajo de grado en la modalidad de pasantía desarrollado; por las estudiantes Carolina López Díaz y Andrea María Perozo bajo la dirección de la docente Martha Torres de Tovar, como requisito para optar por el título de Terapeutas Ocupacionales. Este, es un intento por acercar el conocimiento profesional fundamentado en el contexto, el hombre, la ocupación y el desempeño ocupacional al campo de la orientación ocupacional-profesional en el sector educativo, con el propósito de construir una instancia que fortalezca la escolaridad de secundaria en términos de la ocupación de estudiantes del grado décimo y facilite el paso al medio laboral a través de la elección acertada de una profesión.

Abstract Little is known about the features and outcomes of Brazilian patients with pancreatic cancer. We sought to describe the socio-economic characteristics, patterns of health care access, and survival of patients diagnosed with malignant pancreatic tumors from 2000 to 2014 in São Paulo, Brazil. We included patients with malignant exocrine and non-classified pancreatic tumors according to the International Classifications of Disease (ICD)-O-2 and -O-3, diagnosed from 2000 to 2014, who were registered in the FOSP database. Prognostic factors for overall survival (OS) in the subgroup of patients with ductal or non-specified (adeno)carcinoma were evaluated using Cox proportional hazard model. The study population consists of 6855 patients. Median time from the first visit to diagnosis and treatment were 13 (Interquartile range [IQR] 4–30) and 24 (IQR 8–55) days, respectively. Both intervals were longer for patients treated in the public setting. Median OS was 4.9 months (95% confidence interval [95% CI] 4.7–5.2). Increasing age, male gender, lower educational level, treatment in the public setting, absence of treatment, advanced stage, and treatment from 2000 to 2004 were associated with inferior OS. From 2000–2004 to 2010–2014, no improvement in OS was seen for patients treated in the public setting. Survival of patients with malignant pancreatic tumors remains dismal. Socioeconomical variables, especially health care funding, are major determinants of survival. Further work is necessary to decrease inequalities in access to medical care for patients with pancreatic cancer in Brazil.

The heterogeneity of response to neoadjuvant chemoradiotherapy (NCRT) is still a challenge in locally advanced rectal cancer (LARC). The evaluation of thymidylate synthase (TYMS) and RAD23 homolog B (RAD23B) expression in circulating tumor cells (CTCs) provides complementary clinical information. CTCs were prospectively evaluated in 166 blood samples (63 patients) with LARC undergoing NCRT. The primary objective was to verify if the absence of RAD23B/TYMS in CTCs would correlate with pathological complete response (pCR). Secondary objectives were to correlate CTC kinetics before (C1)/after NCRT (C2), in addition to the expression of transforming growth factor-β receptor I (TGF-βRI) with survival rates. CTCs were isolated by ISET and evaluated by immunocytochemistry (protein expression). At C1, RAD23B was detected in 54.1% of patients with no pCR and its absence in 91.7% of patients with pCR (p = 0.014); TYMS− was observed in 90% of patients with pCR and TYMS+ in 51.7% without pCR (p = 0.057). Patients with CTC2 > CTC1 had worse disease-free survival (DFS) (p = 0.00025) and overall survival (OS) (p = 0.0036) compared with those with CTC2 ≤ CTC1. TGF-βRI expression in any time correlated with worse DFS (p = 0.059). To conclude, RAD23B/TYMS and CTC kinetics may facilitate the personalized treatment of LARC.

Objective. To evaluate the HER2 expression on gastric adenocarcinoma from a Brazilian population and also to analyze the relations between the receptor and clinical characteristics, as well as the survival status. Materials and Methods. A retrospective analysis was conducted from January of 2008 to July of 2012, considering only gastrectomies with curative intent. Tumors were tested for HER2 status using immunohistochemistry. The relation between HER2 status and clinical aspects, surgical findings, and survival were also analyzed. Results. 222 patients with gastric carcinoma were submitted to surgery during that period, but only 121 (54,5%) were with curative intention. The immunohistochemistry revealed that 4 patients (3,3%) were HER2-positive, 6 patients (4,9%) HER2-undetermined, and 111 patients (91,7%) HER2-negative. There was no statistical concordance between HER2 status and survival or the clinical aspects. Conclusion. The HER2 overexpression rate was very low in this Brazilian population sample and cannot be considered as a prognostic factor.

Observa-se o aumento do número de óbitos tipo suicídio no país, em indivíduos envelhescentes. O trabalho consiste em levantar e comparar dados referentes a estes óbitos, em indivíduos entre 40 e 60 anos, no Estado do Rio de Janeiro. A metodologia baseia-se na investigação quantitativa com análise dos dados obtidos no Sistema de Informação sobre Mortalidade, no período de 2000 a 2005. Esses dados permitem identificar que os suicídios nestes indivíduos aparecem de forma expressiva.

The thyroid hormone receptor (TR) is essential for the proper regulation of metabolism and development, as it regulates gene expression in response to thyroid hormone. Nuclear localization signals (NLSs) and nuclear export signals (NESs) allow for TR transport into and out of the nucleus, respectively. Previous research suggests that nuclear import, nuclear retention, and nuclear export of TR are associated with modulation of gene expression, the alteration of which can contribute to various diseases. Here, we examined the impact of cancer-associated mutations on TR localization patterns as a way of analyzing key structural components of TR and to further explore the correlation between TR trafficking, misfolding, and disease. Through mammalian cell transfection of expression plasmids for green fluorescent protein (GFP) and mCherry-tagged TRα1 and quantitative fluorescence microscopy, we examined particular groups of TRα1 mutations that were observed in patients with hepatocellular carcinoma, renal cell carcinoma, and thyroid cancer, and are associated with NLSs and NESs of TRα1. We also investigated structural alterations of the mutants by in silico modeling. Our results show striking shifts towards a more cytoplasmic localization for many of the mutants and an increased tendency to form cytosolic and nuclear aggregates., Competing Interests: Competing Interests The authors declare no competing interests.

Objective . To evaluate the HER2 expression on gastric adenocarcinoma from a Brazilian population and also to analyze the relations between the receptor and clinical characteristics, as well as the survival status. Materials and Methods . A retrospective analysis was conducted from January of 2008 to July of 2012, considering only gastrectomies with curative intent. Tumors were tested for HER2 status using immunohistochemistry. The relation between HER2 status and clinical aspects, surgical findings, and survival were also analyzed. Results . 222 patients with gastric carcinoma were submitted to surgery during that period, but only 121 (54,5%) were with curative intention. The immunohistochemistry revealed that 4 patients (3,3%) were HER2-positive, 6 patients (4,9%) HER2-undetermined, and 111 patients (91,7%) HER2-negative. There was no statistical concordance between HER2 status and survival or the clinical aspects. Conclusion . The HER2 overexpression rate was very low in this Brazilian population sample and cannot be considered as a prognostic factor., Competing Interests: The authors declare no competing interests.