The Nß motif of NaTrxh directs secretion as an endoplasmic reticulum transit peptide and variations might result in different cellular targeting.

Soluble secretory proteins with a signal peptide reach the extracellular space through the endoplasmic reticulum-Golgi conventional pathway. During translation, the signal peptide is recognised by the signal recognition particle and results in a co-translational translocation to the endoplasmic reticulum to continue the secretory pathway. However, soluble secretory proteins lacking a signal peptide are also abundant, and several unconventional (endoplasmic reticulum/Golgi independent) pathways have been proposed and some demonstrated. This work describes new features of the secretion signal called Nß, originally identified in NaTrxh, a plant extracellular thioredoxin, that does not possess an orthodox signal peptide. We provide evidence that other proteins, including thioredoxins type h, with similar sequences are also signal peptide-lacking secretory proteins. To be a secretion signal, positions 5, 8 and 9 must contain neutral residues in plant proteins-a negative residue in position 8 is suggested in animal proteins-to maintain the Nß motif negatively charged and a hydrophilic profile. Moreover, our results suggest that the NaTrxh translocation to the endoplasmic reticulum occurs as a post-translational event. Finally, the Nß motif sequence at the N- or C-terminus could be a feature that may help to predict protein localisation, mainly in plant and animal proteins.

Multidrug-resistant Raoultella ornithinolytica misidentified as Klebsiella oxytoca carrying blaOXA ß-lactamases: antimicrobial profile and genomic characterization.

Class D ß-lactamases OXA-232 and OXA-48 hydrolyze penicillin, cephalosporins and carbapenems, limiting the pharmacological therapeutics in bacteraemia. OXA producer microorganisms are considered a great emergent threat, especially in nosocomial environments. To determine the resistance profile and genomic characterization of two isolates initially identified as potential carbapenemase-producer Klebsiella oxytoca in a third level hospital. Automated platform BD Phoenix-100 System was used to identify and to biochemically characterize both isolates. Furthermore, the resistance profile was determined through CLSI methods and the whole genome sequences were obtained using Next-Generation Sequencing. Resistance genes were analyzed, and the virtual fingerprinting was determined to corroborate the similarity with related bacteria. Both strains correspond to Raoultella ornithinolytica carrying OXA 232 and OXA-48 genes, confirming the class D ß-lactamases assay results. Here, we present the genetic and phenotypic analysis of multidrug resistance R. ornithinolytica, representing the first report in Mexico.

Klebsiella pneumoniae blaNDM-1 carrying a class 1 integron causing a hospital outbreak in a Mexican attention center.

INTRODUCTION: Infections acquired in hospitals are the cause of high morbidity and mortality and with the emergence of resistant bacteria, the problem is greater. The aim of this work was to determine the genetic characteristics and timeline of Klebsiella pneumoniae blaNDM-1 carrying a class 1 integron involved in an intrahospital outbreak. METHODOLOGY: Investigation was made from the first detection of K. pneumoniae blaNDM-1, strain "466", and the last clone "423". 16S rRNA gene analysis showed that 466 strain and clones were related to K. pneumoniae. Extended-spectrum ß-lactamases (ESBL) was detected according to the Clinical and Laboratory Standards Institute (CLSI) and real time-PCR. Typing of K. pneumoniae blaNDM-1 strains was carried by ERIC-PCR and sequencing the variable region of the integrons were performed. RESULTS: A cluster of six resistant isolates of K. pneumoniae blaNDM-1 was detected in intensive care unit (ICU), internal medicine (IM) and orthopedics (OT). Timeline revealed that the first bacterial identification was in ICU and the last clone in OT service. The array genetic of variable region was "IntI/aadA5-drfA17/qacEΔ1-Sul1". CONCLUSIONS: The evidences highlight the importance of the epidemiological surveillance of Extended-spectrum ß-lactamases (ESBL) strains, as well as the need for molecular epidemiological studies to identify the routes of transmission and the contamination sources within health personnel.

Homicide Epidemic in Cali, Colombia: A Surveillance System Data Analysis, 1993‒2018.

Objectives. To examine homicide rates in Cali, Colombia, during the 1993-2018 period, using information derived from an interagency surveillance system. Methods. We used homicide data from Cali's Epidemiological Surveillance System to examine homicide trends by victim's age and sex, time, and type of method used. We estimated trend changes and the annual percentage changes using joinpoint regression analyses. Results. Homicide rates per 100 000 inhabitants dropped from 102 in 1993 to 47.8 in 2018. We observed reductions in homicide rates across age and sex groups. Most homicide victims were men aged 20 to 39 years from poor, marginalized areas. Firearms were used in 84.9% of all cases. The average annual percentage change for the entire period was -3.6 (95% confidence interval = -6.7, -0.4). Conclusions. Fluctuations in homicide rates in Cali show a clear epidemic pattern, occurring concurrently with the "crack epidemic" in different countries. Reliable and timely information provided by an Epidemiological Surveillance System allowed opportune formulation of public policies to reduce the impact of violence in Cali.

[Results of the Program for the Rational Use of Antimicrobials in a Mexican hospital, 2013-2018Resultados de um programa para o uso racional de antimicrobianos num hospital no México, 2013-2018]. / Resultados del Programa de Uso Racional de Antimicrobianos en un hospital de México, 2013-2018.

OBJECTIVE: Describe the results of the Program for the Rational Use of Antimicrobials at Mexico's Juárez Hospital. METHODS: An observational, cross-sectional, retrospective, descriptive study was designed. For the consumption of antimicrobial agents, data from January 2013 to December 2018 were analyzed by calculating the defined daily dose (DDD). For the cost analysis, a traditional costing calculation was used. RESULTS: For the group of carbapenem agents, there was a sizeable reduction in the consumption of imipenem / cilastatin: the DDD declined from 2.3 in 2013 to 0.7 in 2018, a decrease of 70%. By contrast, for the other two agents, increases were observed. The consumption of meropenem increased by 2% (from 2.4 in 2013 to 2.5 in 2018); the consumption of ertapenem increased by 75% (from 1 in 2013 to 1.8 in 2018). The total expenditure on antimicrobial agents was USD 930 556.46 during 2013, compared to USD 856 079.10 during 2018, representing a difference of 8% or USD 74 905.61 of the total expenditure. CONCLUSIONS: Programs for the rational use of antimicrobials need to be evaluated continuously, by monitoring both consumption of agents by patients and related institutional expenditures.

OBJETIVO: Descrever os resultados do Programa para o Uso Racional de Antimicrobianos no Hospital Juárez de México. MÉTODOS: Elaboramos um estudo observacional, transversal, retrospectivo e descritivo. Analisamos o consumo de antimicrobianos de janeiro de 2013 a dezembro de 2018 pelo cálculo da dose diária definida (DDD); para a análise de custos, realizamos um cálculo de custos tradicional. RESULTADOS: No grupo dos carbapenens, a redução do consumo de imipenem/cilastatina foi notável: passou-se de uma DDD de 2,3 em 2013 para 0,7 em 2018, uma redução de 70%. Por outro lado, observou-se um aumento no uso dos dois outros medicamentos: no caso do meropenem, foi registrado um aumento de 2% (de 2,4 em 2013 a 2,5 em 2018); no consumo de ertapenem o aumento foi de 75% (de 1 em 2013 a 1,8 em 2018). No total, as despesas com antimicrobianos foram de USD 930 556,46 em 2013 e de USD 856 079,10 em 2018, uma diferença de 8%, o que equivale a uma redução de USD 74 905,61 nas despesas totais. CONCLUSÕES: É necessário avaliar continuamente os programas para o uso racional de antimicrobianos pelo monitoramento do consumo e das despesas derivadas.

Resultados del Programa de Uso Racional de Antimicrobianos en un hospital de México, 2013-2018

[RESUMEN]. Objetivo. Describir los resultados del Programa de Uso Racional de Antimicrobianos en el Hospital Juárez de México. Métodos. Se diseñó un estudio de tipo observacional, transversal, retrospectivo y descriptivo. Se analizó el consumo de antimicrobianos de enero de 2013 a diciembre de 2018 a través del cálculo de la dosis diaria definida (DDD); para el análisis de costos se realizó un cálculo de costeo tradicional. Resultados. En el grupo de los carbapenémicos, es notable la reducción en el consumo de imipenem/cilastina: se pasó de una DDD en el 2013 de 2,3 a 0,7 en el 2018, con una reducción de 70%. En cambio, en los otros dos fármacos, se ha observado un incremento. En meropenem se registró de 2% (de 2,4 en 2013 a 2,5 en 2018); en el consumo de ertapenem el incremento es de 75% (de 1 en 2013 a 1,8 en 2018). En total, el gasto de antimicrobianos durante 2013 fue de $930 556,46, mientras que en 2018 fue de $856 079,10, con una diferencia de 8%, lo que equivale a $74 905,61 del gasto total (los valores se expresan en dólares estadounidenses). Conclusiones. Se necesita evaluar de manera constante los programas para el uso racional de antimicrobianos, mediante el monitoreo del consumo y el gasto derivado.

[ABSTRACT]. Objective. Describe the results of the Program for the Rational Use of Antimicrobials at Mexico’s Juárez Hospital. Methods. An observational, cross-sectional, retrospective, descriptive study was designed. For the consumption of antimicrobial agents, data from January 2013 to December 2018 were analyzed by calculating the defined daily dose (DDD). For the cost analysis, a traditional costing calculation was used. Results. For the group of carbapenem agents, there was a sizeable reduction in the consumption of imipenem / cilastatin: the DDD declined from 2.3 in 2013 to 0.7 in 2018, a decrease of 70%. By contrast, for the other two agents, increases were observed. The consumption of meropenem increased by 2% (from 2.4 in 2013 to 2.5 in 2018); the consumption of ertapenem increased by 75% (from 1 in 2013 to 1.8 in 2018). The total expenditure on antimicrobial agents was USD 930 556.46 during 2013, compared to USD 856 079.10 during 2018, representing a difference of 8% or USD 74 905.61 of the total expenditure. Conclusions. Programs for the rational use of antimicrobials need to be evaluated continuously, by monitoring both consumption of agents by patients and related institutional expenditures.

[RESUMO]. Objetivo. Descrever os resultados do Programa para o Uso Racional de Antimicrobianos no Hospital Juárez de México. Métodos. Elaboramos um estudo observacional, transversal, retrospectivo e descritivo. Analisamos o consumo de antimicrobianos de janeiro de 2013 a dezembro de 2018 pelo cálculo da dose diária definida (DDD); para a análise de custos, realizamos um cálculo de custos tradicional. Resultados. No grupo dos carbapenens, a redução do consumo de imipenem/cilastatina foi notável: passou-se de uma DDD de 2,3 em 2013 para 0,7 em 2018, uma redução de 70%. Por outro lado, observou-se um aumento no uso dos dois outros medicamentos: no caso do meropenem, foi registrado um aumento de 2% (de 2,4 em 2013 a 2,5 em 2018); no consumo de ertapenem o aumento foi de 75% (de 1 em 2013 a 1,8 em 2018). No total, as despesas com antimicrobianos foram de USD 930 556,46 em 2013 e de USD 856 079,10 em 2018, uma diferença de 8%, o que equivale a uma redução de USD 74 905,61 nas despesas totais. Conclusões. É necessário avaliar continuamente os programas para o uso racional de antimicrobianos pelo monitoramento do consumo e das despesas derivadas.

Aplanar y exhibir la variación: dos estrategias de investigación de la genética humana en México / Flattening and Unpacking Variation: Two Research Strategies of Human Genetics in Mexico / Aplanar e exibir a variação: duas estratégias de pesquisa da genética humana no México

Resumen Introducción: este artículo analiza dos estrategias de investigación puestas en acción en tres proyectos de estudio de la genética humana en México, entre 1960 y 2009. Se distingue entre una estrategia que incorpora recursos multidisciplinarios en el diseño del muestreo, el análisis e interpretación de datos (a la que se le denomina de exhibición), y una que privilegia consideraciones pragmáticas sobre los análisis multidisciplinarios (a la que se le denomina de aplanamiento). Desarrollo: se analizó el trabajo del médico hematólogo Rubén Lisker en la década de 1960, el mapeo de la diversidad genómica mexicana realizado por investigadores del Instituto Nacional de Medicina Genómica entre 2004 y 2009, y el análisis de la variación nativa llevado a cabo por el genetista Andrés Moreno (en la Universidad de Stanford en ese entonces), y sus colegas en años recientes. Conclusiones: las decisiones estratégicas que toman los científicos tienen consecuencias en la medición y caracterización de la variación genética en las poblaciones humanas, pero también sobre las prácticas sociales demográficas y biomédicas relacionadas con su estudio. Mientras la primera estrategia exhibe de forma detallada la variación genética oculta en las poblaciones humanas, favoreciendo así la precisión y el realismo, la segunda tiende a aplanar las diferencias individuales y a perder profundidad histórica, pero privilegiando la generalización y la descripción de los grandes rasgos de una población.

Abstract Introduction: This article analyzes two research strategies carried out by three projects of human genetics in Mexico, between 1960 and 2009. We distinguish between a strategy that incorporates multidiscipli-nary resources in the design of sampling, analysis and interpretation of data (which we call exhibition), and one that privileges pragmatic considerations on multidisciplinary analysis (which we call flattening). Development: We analyzed the work of the hematologist Rubén Lisker in the 1960s, the mapping of Mexican genomic diversity carried out by researchers from the National Institute of Genomic Medicine between 2004 and 2009, and the analysis of the native variation carried out by geneticist Andrés Moreno (then at Stanford University), and his colleagues in recent years. Conclusions: The strategic decisions taken by scientists have consequences in the measurement and characterization of genetic variation in human populations, but also in the demographic and biomedical social practices related to their study. While the first strategy exhibits detailed genetic variation hidden in human populations, thus favoring precision and realism, the second tends to flatten individual differences and lose historical depth, but privileging the generalization and description of the broad features of a population.

Resumo Introdução: este artigo analisa duas estratégias de pesquisa colocada em prática em três projetos de estudo da genética humana no México, entre 1960 e 2009. Distinguimos entre uma estratégia que incorpora recursos multidisciplinares no desenho da amostragem, a análise e interpretação de dados (à qual chamamos de exibição), e uma que privilegia considerações pragmáticas sobre as análises multidisciplinares (a qual chamamos de aplanamento). Desenvolvimento: analisamos o trabalho do médico hematólogo Rubén Lisker na década de 1960, o mapeamento da diversidade genômica mexicana realizado por pesquisadores do Instituto Nacional de Medicina Genômica (INMEGEN) entre 2004 e 2009, e a análise da variação nativa levado a cabo pelo geneticista Andrés Moreno (para então na Universidade de Stanford), e seus colegas em anos recentes. Conclusões: as decisões estratégicas que tomam os científicos têm consequências na medição e caracterização da variação genética nas populações humanas, mas também sobre as práticas sociais demográficas e biomédicas relacionadas com o seu estudo. Enquanto a primeira estratégia exibe de forma detalhada a variação genética oculta nas populações humanas, favorecendo assim a precisão e o realismo, a segunda tende a aplanar as diferenças individuais e a perder profundidade histórica, mas privilegiando a generalização e a descrição dos grandes rasgos de uma população.

Flattening and Unpacking Human Genetic Variation in Mexico, Postwar to Present.

Argument This paper analyzes the research strategies of three different cases in the study of human genetics in Mexico - the work of Rubén Lisker in the 1960s, INMEGEN's mapping of Mexican genomic diversity between 2004 and 2009, and the analysis of Native American variation by Andrés Moreno and his colleagues in contemporary research. We make a distinction between an approach that incorporates multiple disciplinary resources into sampling design and interpretation (unpacking), from one that privileges pragmatic considerations over more robust multidisciplinary analysis (flattening). These choices have consequences for social, demographic, and biomedical practices, and also for accounts of genetic variation in human populations. While the former strategy unpacks fine-grained genetic variation - favoring precision and realism, the latter tends to flatten individual differences and historical depth in lieu of generalization.

Sobre la supuesta inocuidad del consumo de marihuana: diferencia entre consumidores y no consumidores en encuestas nacionales en Colombia / On the supposed safety of marijuana's consumption: difference between consumers in national surveys in Colombia

Diferentes fuentes muestran que el consumo de marihuana tiene efectos negativos sobre la salud y la convivencia ciudadana. El objetivo del presente estudio fue analizar diferencias entre consumidores y no consumidores de marihuana, en variables que pudieran mostrar la tendencia a afectaciones sociales y de salud, eventualmente asociadas al consumo de la sustancia en cuestión. Se tomaron las bases de datos de los estudios nacionales de consumo de 2008 (población general de 12 a 65 años) y 2011 (población escolarizada entre 12 y 18 años). En la primera población se encontraron diferencias significativas en cuanto a accidentes laborales y consumo de riesgo y perjudicial de alcohol; en la segunda, se encontró un rendimiento académico deficitario e incidentes de agresión, a veces como víctimas, otras como victimarios, entre los consumidores. Los resultados confirman los hallazgos de otros estudios, en los cuales se ha podido establecer que, contrariamente a la creencia común entre muchos consumidores de marihuana, sí hay una asociación entre consumo de esa sustancia y problemas a nivel de conducta y de rendimiento académico. Se sugiere realizar estudios longitudinales para superar las deficiencias metodológicas derivadas de los estudios transversales...

Data from several sources show that marihuana smoking has harmful effects on health and conviviality. The purpose of this study was to analyse the differences between users and non-users of marihuana on variables potentially associated with social and health problems amongst those using marihuana. Two data bases were analyzed: one from 2008, regarding general population (12 to 65 years of age), and a second one from 2011 regarding school populations with ages between 12 and 18. In the first population significant differences were found for work accidents and alcohol abuse; in the second one the differences were related to academic failure and agression incidents, some times as victims, some times as perpetrators. The results confirm other studiesÆ findings: contrary to the common belief among marihuana users, there is a strong association between the use of the substance and behavioral and academic problems. It is suggested that longitudinal studies must be carried out in order to overcome the methodological limitations and flaws related to cross-sectional studies...