Clinical management of severe infections caused by carbapenem-resistant Gram-negative bacteria: a worldwide cross-sectional survey addressing the use of antibiotic combinations.

OBJECTIVES: Optimal treatment of carbapenem-resistant Gram-negative (CR-GNB) infections is uncertain due to the lack of good-quality evidence and the limited effectiveness of available antibiotics. The aim of this survey was to investigate clinicians' prescribing strategies for treating CR-GNB infections worldwide. METHODS: A 36-items-questionnaire was developed addressing the following aspects of antibiotic prescribing: respondent's background, diagnostic and therapeutic availability, preferred antibiotic strategies and rationale for selecting combination therapy. Prescribers were recruited following the snowball-sampling approach, and a post-stratification correction with inverse proportional weights was used to adjust the sample's representativeness. RESULTS: 1012 respondents from 95 countries participated in the survey. Overall, 298 (30%) of respondents had local guidelines for treating CR-GNB at their facility and 702 (71%) had access to Infectious Diseases consultation, with significant discrepancies according to country economic status: 85% (390/502) in High-Income-Countries vs 59% (194/283) in Upper-Medium-Income-Countries and 30% (118/196) in Lower-Middle-Income-Countries/Lower-Income-Countries). Targeted regimens varied widely, ranging from 40 regimens for CR-Acinetobacter spp. to more than 100 regimens for CR-Enterobacteriaceae. Although the majority of respondents acknowledged the lack of evidence behind this choice, dual combination was the preferred treatment scheme and carbapenem-polymyxin was the most prescribed regimen, irrespective of pathogen and infection source. Respondents noticeably disagreed around the meaning of 'combination therapy' with 20% (150/783) indicating the simple addition of multiple compounds, 42% (321/783) requiring the presence of in vitro activity and 38% (290/783) of in vitro-synergism. CONCLUSIONS: Management of CR-GNB infections is far from being standardized. Strategic public health focussed randomised controlled trials are urgently required to inform evidence-based treatment guidelines

Fungal G-protein-coupled receptors::mediators of pathogenesis and targets for disease control

G-protein signalling pathways are involved in sensing the environment, enabling fungi to coordinate cell function, metabolism and development with their surroundings, thereby promoting their survival, propagation and virulence. G-protein-coupled receptors (GPCRs) are the largest class of cell surface receptors in fungi. Despite the apparent importance of GPCR signalling to fungal biology and virulence, relatively few GPCR–G-protein interactions, and even fewer receptor-binding ligands, have been identified. Approximately 40% of current pharmaceuticals target human GPCRs, due to their cell surface location and central role in cell signalling. Fungal GPCRs do not belong to any of the mammalian receptor classes, making them druggable targets for antifungal development. This Review Article evaluates developments in our understanding of fungal GPCR-mediated signalling, while substantiating the rationale for considering these receptors as potential antifungal targets. The need for insights into the structure–function relationship of receptor–ligand interactions is highlighted, which could facilitate the development of receptor-interfering compounds that could be used in disease control

Aspergillus nidulans protein kinase A plays an important role in cellulase production

BACKGROUND: The production of bioethanol from lignocellulosic feedstocks is dependent on lignocellulosic biomass degradation by hydrolytic enzymes. The main component of lignocellulose is cellulose and different types of organisms are able to secrete cellulases. The filamentous fungus Aspergillus nidulans serves as a model organism to study cellulase production and the available tools allow exploring more in depth the mechanisms governing cellulase production and carbon catabolite repression. RESULTS: In A. nidulans, microarray data identified the cAMP-dependent protein kinase A (PkaA) as being involved in the transcriptional modulation and the production of lignocellulolytic enzymes in the presence of cellulose. Deletion of pkaA resulted in increased hydrolytic enzyme secretion, but reduced growth in the presence of lignocellulosic components and various other carbon sources. Furthermore, genes involved in fungal development were increased in the ΔpkaA strain, probably leading to the increased hyphal branching as was observed in this strain. This would allow the secretion of higher amounts of proteins. In addition, the expression of SynA, encoding a V-SNARE synaptobrevin protein involved in secretion, was increased in the ΔpkaA mutant. Deletion of pkaA also resulted in the reduced nuclear localization of the carbon catabolite repressor CreA in the presence of glucose and in partial de-repression when grown on cellulose. PkaA is involved in the glucose signaling pathway as the absence of this protein resulted in reduced glucose uptake and lower hexokinase/glucokinase activity, directing the cell to starvation conditions. Genome-wide transcriptomics showed that the expression of genes encoding proteins involved in fatty acid metabolism, mitochondrial function and in the use of cell storages was increased. CONCLUSIONS: This study shows that PkaA is involved in hydrolytic enzyme production in A. nidulans. It appears that this protein kinase blocks the glucose pathway, hence forcing the cell to change to starvation conditions, increasing hydrolytic enzyme secretion and inducing the usage of cellular storages. This work uncovered new regulatory avenues governing the tight interplay between the metabolic states of the cell, which are important for the production of hydrolytic enzymes targeting lignocellulosic biomass. Deletion of pkaA resulted in a strain with increased hydrolytic enzyme secretion and reduced biomass formation

Modelos explicativos e de intervenção na promoção da saúde do trabalhador Modelos explicativos de intervención en la promoción de la salud del trabajador Explanative and intervention models in workers' health promotion

OBJETIVO: Buscar evidências científicas, na literatura, de modelos explicativos e de intervenção para promoção da saúde do trabalhador e prevenção de acidentes de trabalho com material biológico. MÉTODOS: Revisão integrativa da literatura. RESULTADOS: Onze artigos atenderam aos critérios estabelecidos, 36,4% usaram modelos explicativos centrados no comportamento individual ou possibilitaram a interação entre os indivíduos e prestadores de serviço, 63,6% usaram modelos de intervenção para a promoção da saúde de trabalhadores expostos a riscos biológicos. CONCLUSÃO: Os modelos de intervenção são os mais relevantes na área de saúde do trabalhador, pois direcionam para um modo de dispor os meios técnicos e científicos para intervir sobre riscos e danos à saúde, incorporando uma lógica que orienta as intervenções técnicas sobre os problemas e necessidades dos trabalhadores.<br>OBJETIVO: Buscar evidencias científicas, en la literatura, de modelos explicativos y de intervención para la promoción de la salud del trabajador y prevención de accidentes de trabajo con material biológico. MÉTODOS: Revisión integrada de la literatura. RESULTADOS: Once artículos atendieron a los criterios establecidos, 36,4% usaron modelos explicativos centrados en el comportamiento individual o posibilitaron la interacción entre los individuos y prestadores de servicio, 63,6% usaron modelos de intervención para la promoción de la salud de trabajadores expuestos a riesgos biológicos. CONCLUSIÓN: Los modelos de intervención son los más relevantes en el área de salud del trabajador, pues orientan hacia un modo de disponer los medios técnicos y científicos para intervenir sobre los riesgos y daños a la salud, incorporando una lógica que orienta las intervenciones técnicas sobre los problemas y necesidades de los trabajadores.<br>OBJECTIVE: To search for scientific evidence in literature of explanative and intervention models to promote workers' health and prevent occupational accidents with biological material. METHODS: Integrative literature review. RESULTS: Eleven articles met the inclusion criteria, with 36.4% of them using explanative models centered on the individual behavior or enabling the interaction between individuals and service providers; 63.6% used intervention models to promote the health of workers exposed to biological risks. CONCLUSION: Intervention models are more relevant in the worker health area, since they organize the technical and scientific means to intervene in risks and damage to health, incorporating a logic that guides the technical interventions for the problems and necessities of the workers

Religião e espiritualidade no ensino e assistência de enfermagem Religión y espiritualidad en la educación y asistencia de enfermería Religion and spirituality in education and nursing assistance

Estudo da interseção entre o discurso da enfermagem e os preceitos que albergam a religião/religiosidade e espiritualidade, e como se deu a incorporação e o reflexo desse discurso nas práticas assistenciais, no ensino e no delineamento da organização da profissão. Para revisão bibliográfica, utilizaram-se as bases de dados LILACS e BDENF, da Biblioteca Virtual de Saúde. Um total de 57 artigos completos, publicados entre 1957 e 2007, foram analisados à luz das idéias sobre " memória coletiva" , de Maurice Halbwachs. Verificou-se que há uma raiz religiosa com ramificações profundas na conformação da enfermagem brasileira. Esta configuração está tão imbricada na memória coletiva que, mesmo com a expansão de instituições que não se declaram religiosas, os pressupostos cristãos se mantêm presentes e com vitalidade.<br>Estudio de la intersección entre el discurso del oficio de enfermera y preceptos que alojan la religión/el religiosidad y el espiritualidad, y como ha dado la incorporación y a la consecuencia de este discurso en los asistencias prácticos, la educación y la delineación de la organización de la profesión. Para la revisión bibliográfica, las bases de datos LILACS y BDENF de la Biblioteca Virtual de Salud, fueron utilizadas. Un total de 57 artículos completos, publicados entre 1957 y 2007, fueron analizados a la luz de las ideas en " memoria colectiva" , de Maurice Halbwachs. Se verificó que hay una raíz religiosa con ramificaciones profundas en la conformación del oficio de enfermera brasileño. Esta configuración es tan imbricada en la memoria colectiva que, mismo con la expansión de las instituciones que non se declaran religiosas, el presupuestos cristanos se mantiene presentes y con vitalidad.<br>Intersectional study between nursing discourse and precepts which embrace religion/religiousness and spirituality, and how these were incorporated and their reflection upon nursing practice, education and the history of the organization of the profession. For bibliographic review LILACS and BDENF databases of the Electronic Health Library were used. A total of 57 full-text articles, published from 1957 to 2007, were analyzed upon the light of the ideas of Maurice Halbwachs, about " collective memory" . The results show that Brazilian nursing has a religious root with profound ramifications on its development. This configuration is so embedded in the collective memory that, even with the expansion of non-religious institutions, the Christian precepts remain present and strong