During an infection, one of the principal challenges for the host is to detect the pathogen and activate a rapid defensive response. The Toll-like family of receptors (TLRs), among other pattern recognition receptors (PRR), performs this detection process in vertebrate and invertebrate organisms. These type I transmembrane receptors identify microbial conserved structures or pathogen-associated molecular patterns (PAMPs). Recognition of microbial components by TLRs initiates signaling transduction pathways that induce gene expression. These gene products regulate innate immune responses and further develop an antigen-specific acquired immunity. TLR signaling pathways are regulated by intracellular adaptor molecules, such as MyD88, TIRAP/Mal, between others that provide specificity of individual TLR-mediated signaling pathways. TLRmediated activation of innate immunity is involved not only in host defense against pathogens but also in immune disorders. The involvement of TLR-mediated pathways in auto-immune and inflammatory diseases is described in this review article.

The vancomycin loading dose (LD) of 25 to 30 mg/kg is a frequently practiced strategy to achieve effective concentrations from the first-treatment dose. However, considering only the body weight for dosing might be inadequate in critically ill patients due to pharmacokinetics changes. We sought to assess achieving optimal trough serum levels of vancomycin and AUC 0 -24 /MIC in the first 24 h of treatment by using an LD based on population pharmacokinetic parameters of critically ill patients. We performed a concurrent cohort study over 22 months of patients with severe sepsis who received intravenous vancomycin. The patients were treated with three different strategies to initiate vancomycin: without an LD (group A), with an LD of 25 to 30 mg/kg (group B), and with an LD based on population pharmacokinetic parameters of the critically ill patient (group C). An optimal trough serum concentration was achieved in 5, 9, and 83% of patients in groups A, B, and C, respectively. The number of patients that reached optimal AUC 0 -24 was 2 of 18 (11%), 5 of 11 (46%), and 11 of 12 (92%) in groups A, B, and C, respectively. The statistical analysis for both parameters revealed significant differences in group C with respect to other groups. The administration of the LD calculated from population pharmacokinetic parameters from the beginning of therapy is a more efficient strategy to obtain adequate trough serum concentrations and AUC 0 -24 /MIC in critical patients.

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Inflammatory bowel diseases (IBD) are inflammatory diseases with a multifactorial component that involve the intestinal tract. The two relevant IBD syndromes are Crohn's disease (CD) and ulcerative colitis (UC). One factor involved in IBD development is a genetic predisposition, associated to NOD2/CARD15 and Toll-like receptor 4 (TLR4) polymorphisms that might favor infectious enterocolitis that is possibly associated to the development of IBD. The identification of specific immunologic alterations in IBD and their relationship to the etiology of the disease is a relevant research topic. The role of intra and extracellular molecules, such as transcription factors and cytokines that are involved in the inflammatory response, needs to be understood. The relevance of immunologic molecules that might drive the immune response to a T helper (Th) 1, Th 2 or the recently described Th 17 phenotype, has been demonstrated in animal models and clinical studies with IBD patients. CD and UC predominantly behave with a Th 1 and Th 2 immune phenotype, respectively. Recently, an association between CD and Th 17 has been reported. The knowledge acquired from immunologic and molecular research will help to develop accurate diagnostic methods and efficient therapies (Rev Méd Chile 2008; 136: 367-75). (

We were able to validate the international recommendations on the diagnostic accuracy of this simple combination of two tests in serum for monoclonal gammopathy.

RESUMENEl artículo describe una propuesta de visualización exploratoria e interactiva para modelos de minería de datos generado con la técnica regla de asociación, aplicándole la técnica Self-Organizing Map (SOM) sobre cada componente o regla, junto a vistas proporcionadas por elementos gráficos implementados para complementar esta visualización. Esto busca establecer esquemas de visualización, que soporten la exploración visual del modelo en la etapa de ajuste del modelo de un proceso de minería de datos, y con esto responder preguntas genéricas de analistas de datos respecto del funcionamiento interno del modelo, y lograr apoyar en la comprensión del modelo generado. Este esquema de visualización propuesto se implementa por medio de un software experimental donde los analistas de datos disponen de diversos mecanismos de interacción que les permiten interactuar y explorar cada componente del modelo, con las vistas complementarias descritas con anterioridad. Finalmente, se analizan los resultados obtenidos desde un experimento controlado, llevado a cabo con un grupo de usuarios, y cuyo análisis preliminar de esta evaluación permite, por un lado, corroborar la utilidad del esquema de visualización propuesto sobre modelos de reglas de asociación, y su nivel de eficiencia en apoyar la comprensión del modelo generado.Palabras clave: Minería de datos, minería de datos visual, visualización de modelos de minería de datos, visualización de reglas de asociación. ABSTRACTThe paper describes a proposal for interactive visualization for exploratory data mining models generated with association rule technique, applying the Self-Organizing Map (SOM) technique on each component or rule, with a view provided by graphic elements implemented to complement this visualization. This seeks to establish visualization schemes, which support the visual exploration stage model fit of a data mining process, and with this answer generic questions regarding data analysts inner workings of the model, and achieve support in understanding generated model. This proposed scheme is implemented visualization through experimental software where data analysts have different interaction mechanisms that allow them to interact and explore each component model, with additional views described above. Finally, results from a controlled experiment, conducted with a group of users whose preliminary analysis of this evaluation allow one hand confirm the usefulness of the proposed scheme on display models of association rules, and analyzes level of efficiency in support understanding of the generated model.

Multiple myeloma (MM) is a plasma cell dyscrasia characterized by bone marrow plasma cell infiltration and the secretion of monoclonal immunoglobulin (Ig) in the serum or urine. Median survival in MM patients is approximately 5 years and significant morbidity may be experienced. The course is progressive and although, always incurable, the prognosis is highly variable. The two more widely used staging systems in MM are by Durie and Salmon and the International Staging System (ISS). Others have been studied, including serum free light chain (sFLC) concentrations and ratio (sFLCr). Methods: We measured sFLC in 27 newly diagnosed MM (21 Intact Ig MM, 5 light chain MM, 1 non secretory MM) at our center (Hospital del Salvador, Santiago de Chile) from October 2013 until June 2015. The sFLCr was calculated with the involved monoclonal light chain as the numerator. The median sFLCr was 17. Patients were divided into a "low group" (<17 sFLCr) and a "high group" (>17 sFLCr). We also analyzed these patients using the cut off (sFLCr of 50) previously reported by Garcia de Veas Silva et al. [Hematology reports 2015; 7 (s1) p23] The median follow-up was 16 months. Results: During the period of study there were 8 deaths (29,7%). Seven (87,5%) of these deaths presented with an ISS score of 3 (table 1). Mortality rates were lower in the group of patients with "low" sFLCr (15,3%, 2 deaths in a group of 13 patients), as compared to patients with a "high" sFLCr (42,9%, 6 deaths in a group of 14 patients) (table 2). Using the cutoff established by Garcia de Veas Silva et al, the mortality rate for patients with sFLCr >50 was 66,7% vs. 11,1% in for patients in the <50 sFLCr group (table 3). Discussion: Although a short follow up period was available for analysis, we believe these results are promising. sFLCr can be used as an easy prognostic indicator in newly diagnosed, symptomatic MM, especially when high risk patients (>50 sFLCr) are identified. The introduction of biomarkers in the evaluation of MM patients will enable better risk assessment and rational follow up. Table 1. International Staging System. Stratification of our study population. ISS N Patients N Deaths Mortality (%) 1 2 0 0 2 12 1 8,3 3 13 7 53,9 Table 2. Mortality rate in our study population using the median sFLCr as a cut off value. Mortality MM N Patients N Deaths Mortality (%) All 27 8 29,6 sFLCr>17 14 6 42,9 sFLCr<17 13 2 15,4 Table 3. Mortality rate in our population using the published cut off sFLCr value. Mortality MM N Patients N Deaths Mortality (%) All 27 8 29,6 sFLCr>50 9 6 66,7 sFLCr<50 18 2 11,1 Disclosures Delgado: The Binding Site: Employment.

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