Synthesis, purification and crystallization of a putative critical bulge of HAR1 RNA.

Non-coding RNAs have raised a lot of interest because of their capabilities to perform enzymatic reactions and regulate gene expression in various ways. Human Accelerated Region 1 (HAR1) has been identified during the search for highly conserved regions in mammalian genomes, over one hundred base pairs long, and with high rates of substitution in the human genome. Its potential for coding for a protein is very minimal. However, the HAR1 transcript has been computationally predicted to have a stable secondary structure. Previous structure-probing experiments have suggested that the majority of differences between human and chimp constructs are in helices, designated C and D. For this reason, a 47nt construct consisting of the C and D helices along with two additional C-G pairs was synthesized, purified, and crystallized, and its x-ray structure is reported in this study. The final structure is an artificial dimer, with a bulge that forms different conformations on each monomer. This bulge has been observed in predicted secondary structures, footprinting assays, enzymatic degradation assays, NMR studies, in silico studies, and in this crystalized dimer structure. It is proposed that the HAR1 transcript is a non-coding RNA that interacts with an unknown binding partner responsible for brain development through this inherent structural motif of bulged adenosines.

Quantification of α-Acids in Fresh Hops by Reverse-Phase High-Performance Liquid Chromatography.

This publication describes a method for the quantification by high-performance liquid chromatography (HPLC) of resinous compounds known as α-acids found in freshly harvested, unprocessed hops. This method provides consistent, efficient, and accurate results as well as the theories and rationale involved in HPLC method development. A system of quality checks was utilized as well as the validation of numerous developmental variables. By starting with a theoretical approach in preparation, extraction, and instrumental techniques and then further developing these practices by experimentation, a reproducible method was developed. Following the validation, fresh cascade hops grown in Sonoma County were analyzed during the 2017 harvest season and found to be within the predicted range specific to this cultivar. This method encompasses the techniques necessary to analyze fresh or dried hops, considering variability between different laboratories.

[Pneumonia associated with mechanical ventilation. Update and recommendations inter- Societies SADI-SATI]. / Neumonía asociada a ventilación mecánica. Actualización y recomendaciones inter-sociedades, Sociedad Argentina de Infectología - Sociedad Argentina de Terapia Intensiva.

Representatives of the Argentine Society of Infectious Diseases (SADI) and the Argentine Society of Intensive Therapy (SATI) worked together on the development of specific recommendations for the diagnosis, treatment and prevention of ventilator-associated pneumonia (VAP). The methodology used was the analysis of the literature published in the last 15 years, complemented with the opinion of experts and local data. This document aims to offer basic tools to optimize diagnosis based on clinical and microbiological criteria, orientation in empirical and targeted antibiotic schemes, news on posology and administration of antibiotics in critical patients and to promote effective measures to reduce the risk of VAP. It also offers a diagnostic and treatment algorithm and considerations on inhaled antibiotics. The joint work of both societies -infectious diseases and intensive care- highlights the concern for the management of VAP and the importance of ensuring improvement in daily practices. This guideline established recommendations to optimize the diagnosis, treatment and prevention of VAP in order to reduce morbidity and mortality, days of hospitalization, costs and resistance to antibiotics due to misuse of antimicrobials.

Neumonía asociada a ventilación mecánica: Actualización y recomendaciones inter-sociedades, Sociedad Argentina de infectología - Sociedad Argentina de terapia intensiva / Pneumonia associated with mechanical ventilation. Update and recommendations inter- Societies SADI-SATI

Representantes de la Sociedad Argentina de Infectología (SADI) y la Sociedad Argentina de Terapia Intensiva (SATI) se unieron para trabajar en la elaboración de recomendaciones de diagnóstico, tratamiento y prevención de la neumonía asociada a ventilación mecánica (NAVM). La metodología utilizada fue el análisis de la bibliografía publicada en los últimos 15 años, complementada con la opinión de expertos y los datos locales. En este documento se pretende ofrecer herramientas básicas de optimización del diagnóstico en base a criterios clínicos y microbiológicos, orientación en los esquemas antibióticos empíricos y dirigidos, novedades en posología y administración de antibióticos en pacientes críticos y promocionar las medidas efectivas para reducir el riesgo de NAVM. Asimismo, ofrece un algoritmo de diagnóstico y tratamiento y consideraciones sobre antibióticos inhalados. El trabajo conjunto de ambas sociedades, infectólogos y terapistas, pone en evidencia la preocupación por el manejo de la NAVM y la importancia de velar por la mejora en las prácticas cotidianas. A través de esta recomendación se establecen pautas locales para optimizar el diagnóstico, tratamiento y prevención de la NAVM con el objeto de disminuir la morbimortalidad, días de internación, costos y resistencia a antibióticos debida al mal uso de los antimicrobianos.

Representatives of the Argentine Society of Infectious Diseases (SADI) and the Argentine Society of Intensive Therapy (SATI) worked together on the development of specific recommendations for the diagnosis, treatment and prevention of ventilator-associated pneumonia (VAP). The methodology used was the analysis of the literature published in the last 15 years, complemented with the opinion of experts and local data. This document aims to offer basic tools to optimize diagnosis based on clinical and microbiological criteria, orientation in empirical and targeted antibiotic schemes, news on posology and administration of antibiotics in critical patients and to promote effective measures to reduce the risk of VAP. It also offers a diagnostic and treatment algorithm and considerations on inhaled antibiotics. The joint work of both societies -infectious diseases and intensive care- highlights the concern for the management of VAP and the importance of ensuring improvement in daily practices. This guideline established recommendations to optimize the diagnosis, treatment and prevention of VAP in order to reduce morbidity and mortality, days of hospitalization, costs and resistance to antibiotics due to misuse of antimicrobials.

Bacteriemias por bacilos Gram negativos multirresistentes en neutropénicos febriles con enfermedades hematológicas / Bacteremia due to multiresistant Gram-negative bacilli in febrile neutropenic patients with hematological diseases

Las infecciones por bacilos Gram negativos multiresistentes (BGN-MR) son frecuentes en nuestro hospital. Presentan limitadas opciones terapéuticas e importante impacto en la morbimortalidad y costos. Objetivo: analizar los factoes de riesgo y evolución de las bacteriemias por BGN-MR en pacientes neutropénicos febriles con patologías hematológicas. Materiales y métodos: estudio prospectivo, descriptivo y observacional de los factores de riesgo para BGN-MR en la población descripta. Se realizó análisis univariado y multivariado de variables clínicas, epidemiológicas, microbiológicas y evolutivas. Resultados: El 27 % de los episodios de neutropenia y fiebre cursaron con bacteriemias por BGN, 42 % de ellos fueron producidos por BGN-MR. En el análisis univariado, dichas bacteriemias se asociaron al uso previo de antibióticos; a las bacteriemias de brecha y neutropenias mayores a 7 días. En el análisis multivariado la bacteriemia de brecha mantuvo su significancia estadística (P<0,001; OR: 5,17; IC 95 % 2,1-12,7). Acinetobacter spp fue el BGN-MR más frecuentemente aislado incluso en los pacientes fallecidos. No se detectó el foco en el 45,9 % de los episodios. Los tratamientos inadecuados fueron significativamente más frecuentes en los pacientes con BGN-MR y la mortalidad tanto global como atribuible también se asoció significativamente al tratamiento inadecuado de las bacteriemias por BGN-MR (P<0,04;RR: 2,46;IC 95 % 1,03-5,9 y P< 0,014; RR: 3,02; IC 95 % 1,22-0,45 respectivamente). Conclusiones: Las bacteriemias por BGN-MR son frecuentes en la población estudiada en especial los que han recibido ATB previo y en las que surgen intratratamiento ATB. Recibieron con mayor frecuencia tratamiento empírico inadecuado, lo que se asoció a mayor mortalidad...

Bacterial infections by multiresistant Gram-negative bacilli (BGN-MR) are an increasing problem in our hospital with a major impact on morbidity, mortality and costs. Objective: to analize risk factors and outcome in bacteremia due to multiresistant Gram-negative bacilli in febrile neutropenic patients with hematologic diseases. Material and Methods: We conducted a prospective, descriptive and observational study to describe the risk factors and outcome of BGN-MR bacteremia in these patients. Results: Twenty seven percent of neutropenia and fever episodes had Gram-negative bacilli bacteremia and 42 % of them were caused by BGN-MR. Previous use of antibioteics, breakthrough bacteremia and prolonged neutropenia (<7 days) were significant in univariate analysis. In multivariate analysis only breakthrough bacteremia was significant (P< 0.001; OR 5,17;IC 95 % 2.1-12.7). Acinetobactersppp was the most common BGN-MR isolated in blood-stream infections and in patients who died. The source of infections was unknown in 45,9 % of the episodes. Inadequate empirical therapy was most common in BGN-MR bacteremia and it was associated with increased overall and attributable mortality (P<0.04; RR: 2.46; IC 95 % 1.03-5.9 y P<0.014; RR: 3.02; IC 95 % 1.22-7.45). Conclusions: BGN-MR was frequent in neutropenic patients with hematological diseases specially in those exposed to antibiotics and in breakthroug bacteremia. Inappropiate antimicrobial therapy was common and is associated with adverse outcome...

[First Travel Medicine Center in a public hospital from Buenos Aires Province, Argentina Republic: The first 2 years of experience]. / Primer Centro de Medicina del Viajero en un hospital público de la Provincia de Buenos Aires, República Argentina: Dos años de experiencia.

INTRODUCTION: Although Buenos Aires is the biggest province in Argentina, there was no program for Travel Medicine in any public hospital until 2008, when the Travel Medicine Center (CEMEVI) was established in our hospital. OBJECTIVE: To analyze the first 24 months of experience in the CEMEVI. RESULTS: A total of 278 travelers were assisted. Most of them consulted before traveling (pre-travel visits). The most common destinations were countries in South America and urban as well as rural areas. Travelling to malaria and yellow fever endemic countries represented 35% and 16% of the total of destinations, respectively. Only 4% were post-travel interviews. CONCLUSION: It is feasible and fruitful to implement a Travel Medicine Center in the public health system.

Primer Centro de Medicina del Viajero en un hospital público de la Provincia de Buenos Aires, República Argentina: Dos años de experiencia / First Travel Medicine Center in a public hospital from Buenos Aires Province, Argentina Republic: The first 2 years of experience

Introduction: Although Buenos Aires is the biggest province in Argentina, there was no program for Travel Medicine in any public hospital until 2008, when the Travel Medicine Center (CEMEVI) was established in our hospital. Objective: To analyze the first 24 months of experience in the CEMEVI. Results: A total of 278 travelers were assisted. Most of them consulted before traveling (pre-travel visits). The most common destinations were countries in South America and urban as well as rural areas. Travelling to malaria and yellow fever endemic countries represented 35% and 16% of the total of destinations, respectively. Only 4% were post-travel interviews. Conclusion: It is feasible and frutful to implement a Travel Medicine Center in the public health system.

Introducción: La Provincia de Buenos Aires, a pesar de ser la mayor de nuestro país, no contaba con ningún sitio de asesoramiento al viajero instalado en un hospital público, hasta que en el año 2008 se crea el Centro de Medicina del Viajero (CEMEVI) en nuestro hospital. Objetivo: analizar de manera retrospectiva los primeros 24 meses de experiencia en el CEMEVI. Resultados: Recibimos un total de 278 consultas, la mayoría durante el pre-viaje, a países de América del Sur, a sitios urbanos- rurales, de los cuales 35 y 16% de los viajeros visitaron zonas de riesgo para malaria y fiebre amarilla, respectivamente. Sólo 4% de las consultas fueron en el post-viaje. Conclusión: Es posible y fructífero implementar un Centro de Medicina del Viajero en el sector público de salud.

RNAi and small interfering RNAs in human disease therapeutic applications.

Small interfering RNAs (siRNAs) have been shown to effectively downregulate gene expression in human cells, giving them potential to eradicate disease. Prospects for clinical applications are discussed in this review, along with an overview of recent history and our current understanding of siRNAs used for therapeutic application in human diseases, such as cancer and viral infections. Over recent years, progress has been made in lipids, ligands, nanoparticles, polymers and viral vectors as delivery agents and for gene-based expression of siRNA to enhance the efficacy and specificity of these methods while at the same time reducing toxicity. It has become apparent that given the recent advances in chemistry and delivery, RNAi will soon prove to be an important and widely used therapeutic modality.

Infección Fúngica oportunista en un trabajador rural viviendo con VIH/sida / Opportunitic funal infection in a rural worker infected with HIV

Las infecciones fúngicas invasivas son una importante causa de morbimortalidad en los pacientes inmunocomprometidos. Diversos factores han producido, en los últimos años, un cambio en la epidemiología de éstas, con aislamiento de hongos infrecuentes hasta hace dos décadas (zygomicetos; Fusarium spp y Scedosporium spp), presentando un desafío diagnóstico y terapéutico. En este reporte describimos un paciente con diagnóstico reciente de VIH/sida, trabajador rural, con antecedentes de fiebre, diarrea y cuadro respiratorio, quien durante la internación presentó un cuadro de neutropenia febril, desarrollando una infección diseminada por Scedosporium prolificans, tratado con éxito con voriconazol.(AU)

Invasive fungal disease is a major cause of morbidity and mortality in immunocompromised patients. Over recent decades numerous factors have contributed to a change in the apidemiology of invasive mycoses. There have been increasing reports of infections due to new and emerging pathogens such as zygomycetes, Fusarium spp and Scedosporium spp, which pose a major diagnostic and therapeutic challenge...(AU)

Infección Fúngica oportunista en un trabajador rural viviendo con VIH/sida / Opportunitic funal infection in a rural worker infected with HIV

Las infecciones fúngicas invasivas son una importante causa de morbimortalidad en los pacientes inmunocomprometidos. Diversos factores han producido, en los últimos años, un cambio en la epidemiología de éstas, con aislamiento de hongos infrecuentes hasta hace dos décadas (zygomicetos; Fusarium spp y Scedosporium spp), presentando un desafío diagnóstico y terapéutico. En este reporte describimos un paciente con diagnóstico reciente de VIH/sida, trabajador rural, con antecedentes de fiebre, diarrea y cuadro respiratorio, quien durante la internación presentó un cuadro de neutropenia febril, desarrollando una infección diseminada por Scedosporium prolificans, tratado con éxito con voriconazol.

Invasive fungal disease is a major cause of morbidity and mortality in immunocompromised patients. Over recent decades numerous factors have contributed to a change in the apidemiology of invasive mycoses. There have been increasing reports of infections due to new and emerging pathogens such as zygomycetes, Fusarium spp and Scedosporium spp, which pose a major diagnostic and therapeutic challenge...

[Nosocomial bloodstream infections caused by gram-negative bacilli: epidemiology and risk factors for mortality]. / Epidemiología y factores de riesgo de mortalidad de las bacteriemias intrahospitalarias por bacilos gramnegativos.

Nosocomial bacteremia is a major cause of hospital infection, associated with high rate of morbidity and mortality, prolonged hospital stay and higher costs. However, few prospective studies analyse the prognostic factors associated with mortality of gramnegative rods bloodstream infections in hospital wards outside of intensive care units. A prospective/descriptive study was conducted from March to December 2006. All patients with nosocomial-acquired bloodstream infection due to gramnegative rods were included. Epidemiology and clinical features were analysed as potential prognostic factors for mortality. During the study period, 84 cases were detected, being A. baumannii, Burkholderia sp and E. coli the most frequent isolates, with a mortality of 48%>. Bacteremia derived from a high-mortality associated septic focus (RR 4.9, IC95%> 1.3 - 18.8) and admission to intensive care unit (RR 4.78, IC95%> 1.7- 13.1) were independent variables associated with mortality. Inappropriate empirical antibiotic treatment was not associated with greater risk of mortality. Nosocomial gramnegative bloodstream infections in our series were mainly due to non-fermentative bacilli and were associated with high mortality rates when their origin was a high risk septic focus or the patient was admitted to intensive care unit.

Capturing hammerhead ribozyme structures in action by modulating general base catalysis.

We have obtained precatalytic (enzyme-substrate complex) and postcatalytic (enzyme-product complex) crystal structures of an active full-length hammerhead RNA that cleaves in the crystal. Using the natural satellite tobacco ringspot virus hammerhead RNA sequence, the self-cleavage reaction was modulated by substituting the general base of the ribozyme, G12, with A12, a purine variant with a much lower pKa that does not significantly perturb the ribozyme's atomic structure. The active, but slowly cleaving, ribozyme thus permitted isolation of enzyme-substrate and enzyme-product complexes without modifying the nucleophile or leaving group of the cleavage reaction, nor any other aspect of the substrate. The predissociation enzyme-product complex structure reveals RNA and metal ion interactions potentially relevant to transition-state stabilization that are absent in precatalytic structures.

Epidemiología y factores de riesgo de mortalidad de las bacteriemias intrahospitalarias por bacilos gramnegativos / Nosocomial bloodstream infections caused by gram-negative bacilli: epidemiology and risk factors for mortality

Nosocomial bacteremia is a major cause of hospital infection, associated with high rate of morbidity and mortality, prolonged hospital stay and higher costs. However, few prospective studies analyse the prognostic factors associated with mortality of gramnegative rods bloodstream infections in hospital wards outside of intensive care units. A prospective/descriptive study was conducted from March to December 2006. All patients with nosocomial-acquired bloodstream infection due to gramnegative rods were included. Epidemiology and clinical features were analysed as potential prognostic factors for mortality. During the study period, 84 cases were detected, being A. baumannii, Burkholderia sp and E. coli the most frequent isolates, with a mortality of 48 percent>. Bacteremia derived from a high-mortality associated septic focus (RR 4.9, IC95 percent> 1.3 - 18.8) and admissionto intensive care unit (RR 4.78, IC95 percent> 1.7- 13.1) were independent variables associated with mortality. Inappropriate empirical antibiotic treatment was not associated with greater risk of mortality. Nosocomial gramnegative bloodstream infections in our series were mainly due to non-fermentative bacilli and were associated with high mortality rates when their origin was a high risk septic focus or the patient was admitted to intensive care unit.

La bacteriemia nosocomial es una causa importante de infección intrahospitalaria, asociada a alta morbi-mortalidad, pero pocos estudios examinan en forma prospectiva las bacteriemias por bacilos grammne-gativos (BGN) más allá de las áreas de cuidados intensivos. Se realizó un estudio descriptivo, prospectivo desde marzo a diciembre del 2006, reclutando todos los pacientes con bacteriemia por BGN de origen intra-hospitalario. Se analiza la epidemiología y características clínicas como potenciales factores pronósticos de mortalidad. En el período de estudio se detectaron 84 casos (los más frecuentes A. baumannii, Burkholderia sp. y E. coli), con una mortalidad de 48 por ciento. La bacteriemia derivada de un foco infecciosos asociada a alta mortalidad (RR 4.9, IC95 por ciento 1,3-18,8) y la internación en UCI (RR 4,78, IC95 por ciento 1,7-13,1) fueron variables independientes predictoras de mortalidad. El tratamiento antimicrobiano empírico inadecuado no se asoció a mayor mortalidad. La bacteriemia nosocomial por BGN en nuestra serie se debió principalmente a bacilos no fermentadores y ésta se asoció con alta mortalidad cuando el origen fue un foco de alto riesgo o el paciente se encontraba internado en la UCI.