The multidrug efflux pump regulator AcrR directly represses motility in Escherichia coli.

Efflux and motility are two key biological functions in bacteria. Recent findings have shown that efflux impacts flagellum biosynthesis and motility in Escherichia coli and other bacteria. AcrR is known to be the major transcriptional repressor of AcrAB-TolC, the main multidrug efflux pump in E. coli and other Enterobacteriaceae. However, the underlying molecular mechanisms of how efflux and motility are co-regulated remain poorly understood. Here, we have studied the role of AcrR in direct regulation of motility in E. coli. By combining bioinformatics, electrophoretic mobility shift assays (EMSAs), gene expression, and motility experiments, we have found that AcrR represses motility in E. coli by directly repressing transcription of the flhDC operon, but not the other flagellum genes/operons tested. flhDC encodes the master regulator of flagellum biosynthesis and motility genes. We found that such regulation primarily occurs by direct binding of AcrR to the flhDC promoter region containing the first of the two predicted AcrR-binding sites identified in this promoter. This is the first report of direct regulation by AcrR of genes unrelated to efflux or detoxification. Moreover, we report that overexpression of AcrR restores to parental levels the increased swimming motility previously observed in E. coli strains without a functional AcrAB-TolC pump, and that such effect by AcrR is prevented by the AcrR ligand and AcrAB-TolC substrate ethidium bromide. Based on these and prior findings, we provide a novel model in which AcrR senses efflux and then co-regulates efflux and motility in E. coli to maintain homeostasis and escape hazards. IMPORTANCE Efflux and motility play a major role in bacterial growth, colonization, and survival. In Escherichia coli, the transcriptional repressor AcrR is known to directly repress efflux and was later found to also repress flagellum biosynthesis and motility by Kim et al. (J Microbiol Biotechnol 26:1824-1828, 2016, doi: 10.4014/jmb.1607.07058). However, it remained unknown whether AcrR represses flagellum biosynthesis and motility directly and through which target genes, or indirectly because of altering the amount of efflux. This study reveals that AcrR represses flagellum biosynthesis and motility by directly repressing the expression of the flhDC master regulator of flagellum biosynthesis and motility genes, but not the other flagellum genes tested. We also show that the antimicrobial, efflux pump substrate, and AcrR ligand ethidium bromide regulates motility via AcrR. Overall, these findings support a novel model of direct co-regulation of efflux and motility mediated by AcrR in response to stress in E. coli.

Comparative analysis of the myoglobin gene in whales and humans reveals evolutionary changes in regulatory elements and expression levels.

Cetacea and other diving mammals have undergone numerous adaptations to their aquatic environment, among them high levels of the oxygen-carrying intracellular hemoprotein myoglobin in skeletal muscles. Hypotheses regarding the mechanisms leading to these high myoglobin levels often invoke the induction of gene expression by exercise, hypoxia, and other physiological gene regulatory pathways. Here we explore an alternative hypothesis: that cetacean myoglobin genes have evolved high levels of transcription driven by the intrinsic developmental mechanisms that drive muscle cell differentiation. We have used luciferase assays in differentiated C2C12 cells to test this hypothesis. Contrary to our hypothesis, we find that the myoglobin gene from the minke whale, Balaenoptera acutorostrata, shows a low level of expression, only about 8% that of humans. This low expression level is broadly shared among cetaceans and artiodactylans. Previous work on regulation of the human gene has identified a core muscle-specific enhancer comprised of two regions, the "AT element" and a C-rich sequence 5' of the AT element termed the "CCAC-box". Analysis of the minke whale gene supports the importance of the AT element, but the minke whale CCAC-box ortholog has little effect. Instead, critical positive input has been identified in a G-rich region 3' of the AT element. Also, a conserved E-box in exon 1 positively affects expression, despite having been assigned a repressive role in the human gene. Last, a novel region 5' of the core enhancer has been identified, which we hypothesize may function as a boundary element. These results illustrate regulatory flexibility during evolution. We discuss the possibility that low transcription levels are actually beneficial, and that evolution of the myoglobin protein toward enhanced stability is a critical factor in the accumulation of high myoglobin levels in adult cetacean muscle tissue.

Successful Pancreatic Cancer Screening Among Individuals at Elevated Risk Using Endoscopic Ultrasound and Magnetic Resonance Imaging: A Community Hospital Experience.

OBJECTIVES: Guidelines for testing individuals at risk (IAR) for developing pancreatic duct adenocarcinoma (PC) are being advanced from university hospital populations. We implemented a screen-in criteria and protocol for IAR for PC in our community hospital setting. METHODS: Eligibility was based on germline status and/or family history of PC. Longitudinal testing continued, alternating between endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI). The primary objective was to analyze pancreatic conditions and their associations with risk factors. The secondary objective was to evaluate the outcomes and complications resulting from testing. RESULTS: Over 93 months, 102 individuals completed baseline EUS, and 26 (25%) met defined endpoints of any abnormal findings in the pancreas. Average enrollment was 40 months, and all participants with endpoints continued standard surveillance. Two participants (1.8%) had endpoint findings requiring surgery for premalignant lesions. Increasing age predicted for endpoint findings. Analysis of longitudinal testing suggested reliability between the EUS and MRI results. CONCLUSIONS: In our community hospital population, baseline EUS was effective in identifying the majority of findings; advancing age correlated with a greater chance of abnormalities. No differences were observed between EUS and MRI findings. Screening programs for PC among IAR can be successfully performed in the community setting.

Interventions to treat methicillin-susceptible Staphylococcus aureus bacteremia: many methodological concerns.

The aim of this letter was to point out some methodological concerns about an article written by Shi et al. and published in the journal. There is an increasing trend in the isolation of Methicillin-susceptible Staphylococcus aureus bacteremia and a variety of questions regarding the best therapy to treat this condition. These concerns might lead to selection, publication and information bias that prevent the generalization and application of these results in our clinical practice.

[Urban outbreak of leishmaniasis in Colombia]. / Brote urbano de leishmaniasis en Colombia.

OBJECTIVES: To describe the epidemiology, clinical characteristics and treatment of children with visceral Leishmaniasis in Neiva- Huila, from April to June 2012. METHODOLOGY: We performed a descriptive study of an outbreak of visceral leshmaniasis in children from the urban area of Neiva. RESULTS: There were seven cases in children younger than five years. All of them had prolonged fever, hepato-splenomegaly, severe anemia and leukopenia. Five were admitted with severe thrombocytopenia, without hemorrhagic manifestations. Six patients received first-line treatment with miltefosine, five of them had treatment failure requirirng therapy escalation to amphotericin B, two received liposomal amphotericin B and three deoxycholate amphotericin B. The main vector identified was the Lutzomyia gomezi and its main reservoir were canines. CONCLUSION: We describe the first visceral leishmaniasis outbreak in children living in an urban area, with no mortality. Most of the cases had a good response to amphotericin B.

OBJETIVOS: Describir las características epidemiológicas, clínicas y el tratamiento de niños con leishmaniasis visceral en Neiva, Huila. METODOLOGIA: Se realizó un estudio descriptivo del brote de leshmaniasis visceral en niños de la zona urbana de Neiva, Huila, entre los meses de abril a junio de 2012. RESULTADOS: Se presentaron siete casos, en niños menores de cinco años, con fiebre prolongada, hepato-esplenomegalia, anemia severa y leucopenia. Cinco ingresaron con trombocitopenia severa, sin manifestaciones hemorrágicas. Seis pacientes recibieron manejo de primera línea con miltefosine, cinco presentaron fracaso terapéutico y se escalonó tratamiento a anfotericina B, de los cuales dos recibieron anfotericina liposomal y tres anfotericina deoxicolato. El principal vector identificado fue la Lutzomyia gomezi y los reservoirios indentifiacados fueron caninos. CONCLUSIÓN: Se describe el primer brote de leishmaniasis visceral en zona urbana, en población pediátrica sin casos de mortalidad. La mayoría de los casos con buena respuesta a Anfotericina B.

Brote urbano de leishmaniasis en Colombia / Urban outbreak of leishmaniasis in Colombia

RESUMEN Objetivos Describir las características epidemiológicas, clínicas y el tratamiento de niños con leishmaniasis visceral en Neiva, Huila. Metodologia Se realizó un estudio descriptivo del brote de leshmaniasis visceral en niños de la zona urbana de Neiva, Huila, entre los meses de abril a junio de 2012. Resultados Se presentaron siete casos, en niños menores de cinco años, con fiebre prolongada, hepato-esplenomegalia, anemia severa y leucopenia. Cinco ingresaron con trombocitopenia severa, sin manifestaciones hemorrágicas. Seis pacientes recibieron manejo de primera línea con miltefosine, cinco presentaron fracaso terapéutico y se escalonó tratamiento a anfotericina B, de los cuales dos recibieron anfotericina liposomal y tres anfotericina deoxicolato. El principal vector identificado fue la Lutzomyia gomezi y los reservoirios indentifiacados fueron caninos. Conclusión Se describe el primer brote de leishmaniasis visceral en zona urbana, en población pediátrica sin casos de mortalidad. La mayoría de los casos con buena respuesta a Anfotericina B.(AU)

ABSTRACT Objectives To describe the epidemiology, clinical characteristics and treatment of children with visceral Leishmaniasis in Neiva- Huila, from April to June 2012. Methodology We performed a descriptive study of an outbreak of visceral leshmaniasis in children from the urban area of Neiva. Results There were seven cases in children younger than five years. All of them had prolonged fever, hepato-splenomegaly, severe anemia and leukopenia. Five were admitted with severe thrombocytopenia, without hemorrhagic manifestations. Six patients received first-line treatment with miltefosine, five of them had treatment failure requirirng therapy escalation to amphotericin B, two received liposomal amphotericin B and three deoxycholate amphotericin B. The main vector identified was the Lutzomyia gomezi and its main reservoir were canines. Conclusion We describe the first visceral leishmaniasis outbreak in children living in an urban area, with no mortality. Most of the cases had a good response to amphotericin B.(AU)

A practical synthesis of xylo- and arabinofuranoside precursors by diastereoselective reduction using Corey-Bakshi-Shibata catalyst.

The Corey-Bakshi-Shibata (CBS) catalyst provides an efficient mechanism to reduce ketones and achieve desired enantiopure alcohols. Herein, the diastereoselective reduction of C-2' and C-3'-keto ribofuranoside derivatives to the corresponding arabino- and xylofuranosides in greater than 95% diastereomeric excess is reported. The stereo-directed substitution with an azido group as well as the synthesis of prodrugs cytarabine and vidarabine are also described. The reported strategy offers superior diastereoselectivity, shorter reaction times, and obviates cooling required with comparable protocols involving achiral reductants.

Estrategias que modulan el síndrome de Burnout en enfermeros (as): una revisión bibliográfica / Strategies that modulate the Burnout syndrome in nurses: a bibliographic review / Estratégias que modulam a síndrome de Burnout em enfermeiros (as): uma revisão de literatura

Introducción: el síndrome de Burnout es la sensación de agotamiento y pérdida de interés por el trabajo que surge en profesionales que mantienen contacto diario con otras personas. Metodología: se realizó una revisión de artículos que reportan estrategias para modular el Burnout en profesionales de enfermería, en las siguientes bases de datos: Scielo, ProQuest, Sciencie Direct, Ovid Nursing, EBSCO, Medline, Pubmed y Wiley Online Library. Los descriptores en español, inglés y portugués utilizados fueron: Burnout, enfermeras, intervenciones. Se encontraron 1.833 artículos, de los cuales 17 cumplieron con los criterios de selección. Resultados: el efecto de las intervenciones pre y post para el Burnout fue medido con el Maslach Burnout Inventory y la Escala de Depresión y Ansiedad Hospitalaria, entre otros. Las intervenciones más reportadas fueron apoyo social, psico-educación, entrenamiento en la solución de problemas y en habilidades de comunicación. 16 artículos reportaron disminución o ausencia del Burnout después de las intervenciones, con cambios en las variables propuestas por Maslach y Jackson o en la sostenibilidad en el tiempo. Conclusión: se reportan estrategias para el Burnout sin distinción de las variables del mismo; sin embargo, se evidencian diferencias en los resultados frente a cambios positivos en cansancio emocional, en comparación con las otras variables.

Introduction: the Burnout syndrome is the feeling of exhaustion and loss of interest in the work that emerges in professionals that maintain daily contact with other people. Methodology: A review of articles that report strategies to modulate the Burnout in nursing professionals was performed in the following databases: Scielo, ProQuest, ScienceDirect, Ovid Nursing, EBSCO, Medline, Pubmed and Wiley Online Library. The descriptors used in Spanish, English and Portuguese were: Burnout, nurses, interventions. 1833 articles were found, in which 17 met the criteria of selection. Results: the effects of pre and post interventions for the Burnout was measured with the Maslach Burnout Inventory and the Hospital Anxiety and Depression Scale, among others. The interventions most reported were social support, psychoeducation, problem solving training and communication skills. 16 articles reported the decrease or absence of Burnout after the interventions, with changes in the variables proposed by Maslach and Jackson or in the sustainability over time. Conclusion: strategies for the Burnout are reported without distinction of the variables; however, differences are evidenced on the results regarding positive changes in emotional tiredness, compared to other variables

Introdução: a síndrome de Burnout é um transtorno adaptativo crônico associado às demandas e exigências laborais, cujo desenvolvimento é insidioso e frequentemente não reconhecido pelo indivíduo, que gera cansaço emocional, sensação de esgotamento e perda de interesse pelo trabalho, principalmente apresentando-se em professionais que mantem contato diário com outras pessoas. Metodologia: realizou-se uma revisão de artigos que reportam estratégias para modular o Burnout em professionais de enfermagem, nas seguintes bases de dados: Scielo, ProQuest, Sciencie Direct, Ovid Nursing, EBSCO, Medline, Pubmed e Wiley Online Library. Os descritores utilizados em espanhol, inglês e português foram: Burnout, enfermeiras, intervenções. Encontraram-se 1.833 artigos, dos quais 17 cumpriram com os critérios de seleção. Resultados: o efeito das intervenções pré e pós para o Burnout foi medido com o Maslach Burnout Inventory e a Escala de Depressão e Ansiedade Hospitalar, entre outros. As intervenções mais reportadas foram apoio social, psico-educação, treinamento na solução de problemas e em habilidades de comunicação. 16 artigos reportaram diminuição ou ausência do Burnout depois das intervenções, com mudanças nas variáveis propostas por Maslach e Jackson ou na sustentabilidade no tempo. Conclusão: se reportam estratégias para o Burnout sim distinção das variáveis do mesmo; porém, se evidenciam diferenças nos resultados frente a mudanças positivas em cansaço emocional, em comparação com as outras variáveis.