Bacteria efflux pumps: characterization and molecular modelisation for which perspectives?

Since their discovery, antibiotic have cured a large number of bacterial infections and improved human life expectancy. However, the use of antibiotics has also led inexorably to the progressive development of bacterial resistance. Among the strategies developed by bacteria to overcome the action of antibiotics, impermeability of the wall and especially active efflux of antibiotics contributed to the emergence of resistance. Efflux pumps are ubiquitous bacterial proteins that recognize in the first place physiological substrates. However, opportunistic antibiotic transport activity by these systems, combined with other resistance mechanisms are responsible for the selection of strains highly resistant to multiple antibiotics, resulting in therapeutic failures. Research data provided by the characterization and molecular modelization of bacterial efflux pumps has been used to define strategies which may lead to the development of new molecules able to inhibit these systems. Meanwhile, new methods for the routine detection of efflux pumps by hospital laboratories are needed to limit the development of high-level multidrug resistance.Depuis la découverte et l'utilisation des antibiotiques, l'antibiothérapie a permis le traitement d'un grand nombre d'infections bactériennes, voire parasitaires et d'améliorer l'espérance de vie humaine. Néanmoins, l'utilisation des antibiotiques a conduit inexorablement au développement progressif de résistances bactériennes. Parmi les stratégies développées par les bactéries pour s'affranchir de l'action souvent létale des antibiotiques, l'imperméabilité de la paroi et en particulier les phénomènes d'efflux actifs des antibiotiques participent à l'émergence de résistances. Les pompes à efflux sont des protéines bactériennes ubiquitaires qui reconnaissent de façon primaire des substrats physiologiques. L'activité de transport opportuniste des antibiotiques par ces systèmes, en association avec d'autres mécanismes de résistance, est responsable de la sélection de souches multi-résistantes de haut niveau à l'origine d'impasses thérapeutiques. Les données récoltées par la caractérisation et la modélisation moléculaire du fonctionnement des pompes à efflux bactériennes, permettent actuellement de définir des stratégies qui pourront conduire au développement de nouvelles molécules capables d'inhiber ces systèmes. En attendant, des méthodes applicables en routine dans les laboratoires hospitaliers doivent être proposées pour détecter les pompes à efflux et limiter ainsi les phénomènes de résistance de haut niveau, redoutés en thérapeutique

Unruptured ectopic pregnancy: diagnosis and treatment. State of art

It is advisable to do the non-invasive diagnosis of ectopic pregnancy precociously, before there is the tube rupture, combining for that the transvaginal ultrasonography with the dosage of the b-fraction of the chorionic gonadotrophin. A range of treatment options may be used. Either a surgical intervention or a clinical treatment may be taken into consideration. Laparotomy is indicated in cases of hemodynamic instability. Laparoscopy is the preferential route for the treatment of tube pregnancy. Salpingectomy should be performed in patients having the desired number of children, while salpingostomy should be indicated in patients willing to have more children, when the b-hCG titers are under 5,000 mUI/mL and the surgical conditions are favorable. The use of methotrexate (MTX) is a consecrated clinical procedure and should be indicated as the first option of treatment. The main criteria for MTX indication are hemodynamic stability, b-hCG 5,000 mUI/mL and no alive embryo. Indication for local treatment with an injection of MTX (1 mg/kg) guided by transvaginal ultrasonography should occur in cases of alive embryos, but with an atypical localization. An expectant conduct should be indicated in cases of decrease in the b-hCG titers within 48 hous before the treatment, and when the initial titers are under 1,500 mUI/mL. There are controversies between salpingectomy and salpingostomy, concerning the reproductive future. Till we reach an agreement in the literature, the advice to patients who are looking forward to a future gestation, is to choose either surgical or clinical conservative conducts.O diagnóstico não invasivo da gravidez ectópica deve ser realizado precocemente, antes de ocorrer a ruptura tubária, combinando a ultra-sonografia transvaginal com a dosagem da fração beta do hormônio gonadotrófico coriônico. Diversas opções de tratamento podem ser utilizadas. Devemos respeitar as indicações tanto das intervenções cirúrgicas como do tratamento clínico. A laparotomia está indicada nos casos de instabilidade hemodinâmica. A laparoscopia é a via preferencial para o tratamento da gravidez tubária. A salpingectomia deve ser realizada nas pacientes com prole constituída. A salpingostomia é indicada nas pacientes com desejo reprodutivo, quando os títulos da b-hCG forem inferiores a 5000 mUI/mL e as condições cirúrgicas forem favoráveis. O tratamento com metotrexato (MTX) é uma conduta consagrada, podendo ser indicado como primeira opção de tratamento. Os principais critérios para indicação do MTX são estabilidade hemodinâmica, b-hCG 5.000 mUI/mL e ausência de embrião vivo. A indicação do tratamento local com injeção de MTX (1 mg/kg) guiada por ultra-sonografia transvaginal é na presença de embrião vivo nos casos de localização atípica. A conduta expectante deve ser indicada nos casos de declínio dos títulos da b-hCG em 48 horas antes do tratamento e quando os títulos iniciais são inferiores a 1.500 mUI/mL. Em relação ao futuro reprodutivo, existem controvérsias entre a salpingectomia e a salpingostomia. Até obtermos um consenso na literatura, orientamos às pacientes desejosas de uma futura gestação a optar pelas condutas conservadoras, tanto cirúrgicas como clínicas.Universidade Federal de São Paulo (UNIFESP) Departamento de ObstetríciaHospital São JoãoUniversidade do Porto Faculdade de MedicinaUniversidade Federal de São Paulo (UNIFESP)UNIFESP, Depto. de ObstetríciaUNIFESPSciEL

An Arduino-Based Talking Calorimeter for Inclusive Lab Activities

UID/QUI/50006/2019 POCI-01-0145-FEDER-007265 PEest/UID/CEC/04516/2019 02/2018/ARNI (International Academic Mobility Program.PMAI) 10/2018/PROPPIT (Course Completion Work Program.PROTCC)This work describes a simple talking calorimeter for the visually impaired based on the Arduino Uno without any shield. An electronic interface was designed using a Wheatstone bridge, a thermistor, or an operational amplifier (opamp). The temperature values are communicated by a loudspeaker connected to pulse-width modulation (PWM) digital output pins 3 and 11 of the Arduino Uno. The system is based on the Talkie library for Arduino Uno. This library was developed using Linear Predictive Coding and includes about 1000 English words. Two new Talkie libraries were constructed, one for Portuguese and another for German. This device can be easily implemented in any teaching laboratory with extremely reduced costs.publishersversionpublishe

An Approach for Reducing the Gap between BPMN Models and Implementation Artifacts

The need for using high-level modeling tools (e.g. BPMN) isincreasing considerably. The proliferation of the service oriented architectures (SOA) is also apparent. In this context, there is a gap between the developed model and its execution. This work introduces the MoSC Translator which translates models produced in BPMN into executable WS-BPEL processes

Towards Generating Richer Code by Binding Security Abstractions to BPMN Task Types

This paper presents an approach for binding security requirements to different BPMN task types to create secure executable business processes.This paper presents an approach for binding security requirements to different BPMN task types to create secure executable business processes

Species which may act as vectors or reservoirs of diseases covered by the Animal Health Law: Listed pathogens of fish

Vector or reservoir species of five fish diseases listed in the Animal Health Law were identified, based on evidence generated through an extensive literature review (ELR), to support a possible updating of Regulation (EU) 2018/1882. Fish species on or in which highly polymorphic region-deleted infectious salmon anaemia virus (HPR∆ ISAV), Koi herpes virus (KHV), epizootic haematopoietic necrosis virus (EHNV), infectious haematopoietic necrosis virus (IHNV) or viral haemorrhagic septicaemia virus (VHSV) were detected, in the field or during experiments, were classified as reservoir species with different levels of certainty depending on the diagnostic tests used. Where experimental evidence indicated transmission of the pathogen from a studied species to another known susceptible species, the studied species was classified as a vector species. Although the quantification of the risk of spread of the pathogens by the vectors or reservoir species was not part of the terms or reference, such risks do exist for the vector species, since transmission from infected vector species to susceptible species was proven. Where evidence for transmission from infected fish was not found, these were defined as reservoirs. Nonetheless, the risk of the spread of the pathogens from infected reservoir species cannot be excluded. Evidence identifying conditions that may prevent transmission by vectors or reservoir fish species during transport was collected from scientific literature. For VHSV, IHNV or HPR∆ ISAV, it was concluded that under transport conditions at temperatures below 25°C, it is likely (66–90%) they will remain infective. Therefore, vector or reservoir species that may have been exposed to these pathogens in an affected area in the wild, aquaculture establishments or through water supply can possibly transmit VHSV, IHNV or HPR∆ ISAV into a non-affected area when transported at a temperature below 25°C. The conclusion was the same for EHN and KHV; however, they are likely to remain infective under all transport temperatures.info:eu-repo/semantics/publishedVersio

Clostridia in Premature Neonates' Gut: Incidence, Antibiotic Susceptibility, and Perinatal Determinants Influencing Colonization

Although premature neonates (PN) gut microbiota has been studied, data about gut clostridial colonization in PN are scarce. Few studies have reported clostridia colonization in PN whereas Bacteroides and bifidobacteria have been seldom isolated. Such aberrant gut microbiota has been suggested to be a risk factor for the development of intestinal infections. Besides, PN are often treated by broad spectrum antibiotics, but little is known about how antibiotics can influence clostridial colonization based on their susceptibility patterns. The aim of this study was to report the distribution of Clostridium species isolated in feces from PN and to determine their antimicrobial susceptibility patterns. Additionally, clostridial colonization perinatal determinants were analyzed.Of the 76 PN followed until hospital discharge in three French neonatal intensive care units (NICUs), 79% were colonized by clostridia. Clostridium sp. colonization, with a high diversity of species, increased throughout the hospitalization. Antibiotic courses had no effect on the clostridial colonization incidence although strains were found susceptible (except C. difficile) to anti-anaerobe molecules tested. However, levels of colonization were decreased by either antenatal or neonatal (during more than 10 days) antibiotic courses (p = 0.006 and p = 0.001, respectively). Besides, incidence of colonization was depending on the NICU (p = 0.048).This study shows that clostridia are part of the PN gut microbiota. It provides for the first time information on the status of clostridia antimicrobial susceptibility in PN showing that strains were susceptible to most antibiotic molecules. Thus, the high prevalence of this genus is not linked to a high degree of resistance to antimicrobial agents or to the use of antibiotics in NICUs. The main perinatal determinant influencing PN clostridia colonization appears to be the NICU environment

Cinema, autoritarismo e política de meios na Argentina: o Festival de Mar del Plata de 1968

Objetivo/contexto: El artículo analiza el proceso de organización del IX Festival Internacional de Cine de Mar del Plata de 1968 y su desarrollo. Se reconstruyen los objetivos que la dictadura del general Juan Carlos Onganía persiguió con la realización de este Festival, hasta entonces organizado por entidades privadas, y también se elaboran las tensiones generadas dentro de la alianza del Gobierno y con grupos del campo cinematográfico. Originalidad: Hasta el momento, la historiografía ha hecho énfasis en la fuerte represión cultural de la dictadura de Onganía. Sin negar esta perspectiva, el análisis de esta experiencia de apertura selectiva aporta nuevas ideas para pensar las políticas culturales y de medios de las dictaduras como estrategia de construcción de consenso interno y legitimación del gobierno en el ámbito de las relaciones internacionales, así como su reverso, el campo cultural como territorio de disputas políticas en el marco de gobiernos autoritarios. Metodología: La investigación fue realizada principalmente a partir del análisis de múltiples publicaciones impresas de la época. Conclusiones: El trabajo propone entender esta experiencia cultural como un proceso de apertura selectivo y restringido, orientado a mejorar la imagen en el exterior del Gobierno a través de la cinematografía. Sin embargo, se trató de una experiencia fallida, porque desde el momento en que se desplegó ese objetivo el Festival se politizó y se presentó como un terreno de disputas entre distintas facciones dentro del Gobierno y del Gobierno con el mundo del cine.Objective/context: The article analyzes the organizational process and execution of the IX Mar del Plata International Film Festival of 1968. It outlines the objectives that General Juan Carlos Onganía’s dictatorship pursued with this festival, which had, until 1968, been organized by private entities. The tensions that arose between the government alliance and cinematographic groups is also discussed. Originality: Until now, historiography has emphasized the strong cultural repression of the Onganía dictatorship. Without denying this perspective, the analysis of this selective opening experience at the film festival brings to the fore new perspectives on how dictatorships used cultural and media policies as an internal consensus building strategy and as a tactic to legitimize the government internationally. Conversely, the cultural arena is seen as a territory for political disputes within the framework of authoritarian governments. Methodology: The research was conducted mainly from the analysis of multiple printed publications of the time. Conclusions: This paper proposes understanding this cultural experience as a process aimed at improving the image of the government abroad through cinematography. However, this attempt by the dictatorship failed because, from the moment that the strategy was launched, the festival became politicized and it was transformed into a terrain of disputes between different factions within the government as well as between the government and the world of cinema.Objetivo/contexto: O artigo analisa o processo de organização do IX Festival Internacional de Cinema de Mar del Plata de 1968 e seu desenvolvimento. São reconstruídos os objetivos que a ditadura do general Juan Carlos Onganía buscou com a realização desse Festival, até então organizado por entidades privadas, assim como são elaboradas as tensões geradas dentro da aliança do Governo e com grupos do campo cinematográfico. Originalidade: Até o momento, a historiografia deu ênfase na forte repressão cultural da ditadura de Onganía. Sem negar essa perspectiva, a análise dessa experiência de abertura seletiva traz novas ideias para pensar as políticas culturais e de meios das ditaduras como estratégia de construção de consenso interno e legitimação do governo no âmbito das relações internacionais, bem como o oposto, o campo cultural como território de disputas políticas no âmbito de governos autoritários. Metodologia: A pesquisa foi realizada principalmente a partir do estudo de diversas publicações impressas da época. Conclusões: O trabalho propõe entender essa experiência cultural como um processo de abertura seletivo e restrito, orientado a melhorar a imagem exterior do Governo através da cinematografia. No entanto, tratou-se de uma experiência malsucedida porque, desde o momento em que surgiu esse objetivo, o Festival se politizou, oferecendo-se como um terreno de disputas entre diferentes facções dentro do Governo e do Governo com o mundo do cinema.Fil: Ramírez Llorens, Fernando Matías. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin