Implementation of a PCR-based strategy to control an outbreak by Serratia marcescens in a Neonatal Intensive Care Unit.

OBJECTIVES: To evaluate the clinical and epidemiological impact of a new molecular surveillance strategy based on qPCR to control an outbreak by Serratia marcescens in a Neonatal Intensive Care Unit (NICU). METHODS: We design a specific qPCR for the detection of S. marcescens in rectal swabs of patients admitted to a NICU. We divided the surveillance study into two periods: (a) the pre-PCR, from the outbreak declaration to the qPCR introduction, and (b) the PCR period, from the introduction of the qPCR until the outbreak was solved. In all cases, S. marcescens isolates were recovered and their clonal relationship was analysed by PFGE. Control measures were implemented during the outbreak. Finally, the number of bloodstream infections (BSI) was investigated in order to evaluate the clinical impact of this molecular strategy. RESULTS: Nineteen patients colonized/infected by S. marcescens were detected in the pre-PCR period (October 2020-April 2021). On the contrary, after the PCR implementation, 16 new patients were detected. The PFGE revealed 24 different pulsotypes belonging to 7 different clonal groups, that were not overlapping at the same time. Regarding the clinical impact, 18 months after the qPCR implementation, no more outbreaks by S. marcescens have been declared in the NICU of our hospital, and only 1 episode of BSI has occurred, compared with 11 BSI episodes declared previously to the outbreak control. CONCLUSIONS: The implementation of this qPCR strategy has proved to be a useful tool to control the nosocomial spread of S. marcescens in the NICU.

Human EWS-FLI protein recapitulates in Drosophila the neomorphic functions that induce Ewing sarcoma tumorigenesis.

Ewing sarcoma (EwS) is a human malignant tumor typically driven by the Ewing sarcoma-Friend leukemia integration (EWS-FLI) fusion protein. A paucity of genetically modified animal models, partially owed to the high toxicity of EWS-FLI, hinders research on EwS. Here, we report a spontaneous mutant variant, EWS-FLI1FS, that circumvents the toxicity issue in Drosophila. Through proteomic and genomic analyses, we show that human EWS-FLI1FS interacts with the Drosophila homologues of EWS-FLI human protein partners, including core subunits of chromatin remodeling complexes, the transcription machinery, and the spliceosome; brings about a massive dysregulation of transcription that affects a significant fraction of known targets of EWS-FLI in human cells; and modulates splicing. We also show that EWS-FLI1FS performs in Drosophila the two major neomorphic activities that it is known to have in human cells: activation of transcription from GGAA microsatellites and out competition of ETS transcription factors. We conclude that EWS-FLI1FS reproduces in Drosophila the known oncogenic activities of EWS-FLI that drive EwS tumorigenesis in humans. These results open up an unprecedented opportunity to investigate EWS-FLI's oncogenic pathways in vivo in a genetically tractable organism.

Conflictos y cambios familiares: significados asociados al consumo de sustancias psicoactivas / Conflicts and family changes: meanings associated with the consumption of psychoactive substances / Conflitos e mudanças familiares: significados associados ao consumo de substâncias psicoativas

Resumen (analítico) Se presentan los contextos sociofamiliares coconstruidos, así como los significados dados al conflicto y a los cambios familiares asociados al consumo de sustancias psicoactivas por parte de un hijo adolescente. Es resultado de una investigación cualitativa-hermenéutica, apoyada en el método de la teoría fundamentada y su interpretación tiene como base epistemológica elementos del construccionismo social. Los resultados muestran movimientos, relaciones y estrategias que marcan: pautas de interacción que conjugan problemas y cambios sociofamiliares, alteraciones emocionales y predominancia de relaciones violentas. Concluye que la agudización del conflicto se da en el marco de relaciones fracturadas de acuerdo con el significado centrado en el rol de padre y madre, patrones relacionales violentos y emociones confusas y contradictorias en las relaciones familiares.

Abstract (analytical) The paper presents co-constructed socio-family contexts, the meanings given to conflict and the family changes associated with the consumption of psychoactive substances by a teenage child. The authors describe the results of a qualitative-hermeneutic investigation supported by the grounded theory method and its interpretation is based on epistemological elements of social constructionism. The results show movements, relationships and strategies related to: patterns of interaction that combine social and family problems and changes; emotional alterations; and the predominance of violent relationships. The authors conclude that the worsening of conflict occurs within the framework of fractured relationships that depend on the meaning related to the roles of parents, violent relational patterns and confused and contradictory emotions in family relationships.

Resumo (analítico) O artigo apresenta os contextos sócio-familiares co-construídos, os significados atribuídos ao conflito e as mudanças familiares associadas ao consumo de substâncias psicoativas por um filho adolescente. É o resultado de uma investigação qualitativa-hermenêutica, apoiada pelo método da teoria fundamentada e com interpretação baseada em elementos epistemológicos do construcionismo social. Os resultados assim como sua análise mostram movimentos, relações e estratégias que marcam: padrões de interação que combinam problemas e mudanças sociais e familiares, alterações emocionais, e predominância de relações violentas. Concluise que o agravamento do conflito ocorre no quadro das relações fraturadas segundo o sentido centrado no papel do pai e da mãe, nos padrões relacionais violentos e nas emoções confusas e contraditórias nas relações familiares.

RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesis.

Ewing sarcoma (EwS) is an aggressive tumor that affects adolescents and young adults. EwS is defined by a chromosomal translocation, EWSR1-FLI1 being the most common, that causes genome reprogramming through remodeling of enhancers. Here, we describe an unexpected function of RING1B, which is highly expressed in EwS. While retaining its repressive activity at Polycomb developmental regulated genes, RING1B colocalizes with EWSR1-FLI1 at active enhancers. We demonstrate that RING1B is necessary for the expression of key EWSR1-FLI1 targets by facilitating oncogene recruitment to their enhancers. Knockdown of RING1B impairs growth of tumor xenografts and expression of genes regulated by EWSR1-FLI1 bound enhancers. Pharmacological inhibition of AURKB with AZD1152 increases H2Aub levels causing down-regulation of RING1B/EWSR1-FLI1 common targets. Our findings demonstrate that RING1B is a critical modulator of EWSR1-FLI1-induced chromatin remodeling, and its inhibition is a potential therapeutic strategy for the treatment of these tumors.

Prácticas dialógicas y códigos sociolingüísticos: crisis y cambios familiares en contextos dialógicos / Dialogical Practices and Sociolinguistic Codes: Crisis and Family Changes in Dialogical Contexts / Práticas dialógicas e códigos sociolinguísticos: crise familiar e alterações nos contextos dialógicos

El presente artículo responde al objetivo central de la investigación de "comprender y explicar las prácticas dialógicas y los códigos sociolingüísticos que han utilizado las familias durante el proceso de superación de situaciones de crisis". Es un estudio cualitativo y hermenéutico, apoyado en los criterios de la Grounded Theoryy en las perspectivas sistémica y socio construccionista. Los testimonios fueron dados por integrantes de 30 familias de los municipios de Manizales, Neira y Risaralda que accedieron voluntariamente a presentar su experiencia. Se concluye que en los movimientos entre la crisis y el cambio hay quiebres en la organización y el funcionamiento familiar, desnaturalización de patrones interaccionales, reconocimientos, aprendizajes personales y sociofamiliares, y la exaltación de los procesos de crisis como potencial para ver aquello que no se debe repetir en sus vidas.

This article responds to the main objective of the research study that it describes: understand and explain the dialogical practices and the sociolinguistic codes used by families during the process of overcoming crisis situations. It is a qualitative hermeneutic study that uses the criteria of Grounded Theory and systemic and social constructionist perspectives. The testimonies were provided by members of 30 families from the municipalities of Manizales, Neira and Risaralda who voluntarily agreed to share their own experiences. It is concluded that in the transition between the crisis and subsequent change there are breakdowns in the functioning of the family and its organization, a denormalization of interaction, recognition and personal patterns, ruptures in socio-family learning and a valuing of the crisis process as having the potential to help them identify what should not be repeated in their lives.

Este artigo responde ao objetivo central da pesquisa: compreender e explicar as práticas dialógicas e códigos sociolinguísticos utilizado por famílias durante o processo de superação de situações de crise. é um estudo qualitativo e hermenéutico apoiado pelos critérios da o Grounded Theory nas perspectivas sistémica e socio-construtivista. Os testemunhos foram dados por membros de 30 famílias nos municípios de Manizales, Risaralda e Neira, que voluntariamente concordaram em apresentar a sua experiência. Conclui-se que os movimentos entre a crise e a mudança apresentam rupturas na organização e funcionamento familiar, a desnaturalização dos padrões interacionais, o reconhecimento, a aprendizagem pessoal e socio-familiar, e a exaltação dos processos de crise como o potencial para ver aquilo que não debe ser repetido na vida.