Women's Knowledge of Genomic Testing and Precision Medicine in Breast Cancer Treatment Decision-Making.

PURPOSE: To understand awareness of genetic and genomic testing, as well as decision-making, in women diagnosed with breast cancer. PARTICIPANTS & SETTING: 29 African American/Black and Latina/Hispanic women diagnosed with breast cancer. METHODOLOGIC APPROACH: A semistructured interview guide was used in focus groups conducted via videoconference. Transcripts were analyzed using thematic analysis. FINDINGS: Many of the women understood the concept of genetic testing to identify the BRCA1/BRCA2 variant, but none of them were aware of genomic testing and its implications for personalized medicine. Participants discussed provider and patient roles in treatment decision-making, identifying roles that the physician might play in treatment planning, from primary decision-maker to collaborator. IMPLICATIONS FOR NURSING: As the number of precision cancer treatments expands, patients must be able to comprehend the information provided to make informed decisions about their treatment. Providers should do a better job of explaining potential treatments so that patients feel they are part of the decision-making process. Addressing gaps in treatment access and uptake requires providers to prioritize patient engagement and understanding.

A cell wall-anchored glycoprotein confers resistance to cation stress in Actinomyces oris biofilms.

Actinomyces oris plays an important role in oral biofilm development. Like many gram-positive bacteria, A. oris produces a sizable number of surface proteins that are anchored to bacterial peptidoglycan by a conserved transpeptidase named the housekeeping sortase SrtA; however, the biological role of many A. oris surface proteins in biofilm formation is largely unknown. Here, we report that the glycoprotein GspA-a genetic suppressor of srtA deletion lethality-not only promotes biofilm formation but also maintains cell membrane integrity under cation stress. In comparison to wild-type cells, under elevated concentrations of mono- and divalent cations the formation of mono- and multi-species biofilms by mutant cells devoid of gspA was significantly diminished, although planktonic growth of both cell types in the presence of cations was indistinguishable. Because gspA overexpression is lethal to cells lacking gspA and srtA, we performed a genetic screen to identify GspA determinants involving cell viability. DNA sequencing and biochemical characterizations of viable clones revealed that mutations of two critical cysteine residues and a serine residue severely affected GspA glycosylation and biofilm formation. Furthermore, mutant cells lacking gspA were markedly sensitive to sodium dodecyl sulfate, a detergent that solubilizes the cytoplasmic membranes, suggesting the cell envelope of the gspA mutant was altered. Consistent with this observation, the gspA mutant exhibited increased membrane permeability, independent of GspA glycosylation, compared to the wild-type strain. Altogether, the results support the notion that the cell wall-anchored glycoprotein GspA provides a defense mechanism against cation stress in biofilm development promoted by A. oris.

Antioxidant Defenses of Francisella tularensis Modulate Macrophage Function and Production of Proinflammatory Cytokines.

Francisella tularensis, the causative agent of a fatal human disease known as tularemia, has been used in the bioweapon programs of several countries in the past, and now it is considered a potential bioterror agent. Extreme infectivity and virulence of F. tularensis is due to its ability to evade immune detection and to suppress the host's innate immune responses. However, Francisella-encoded factors and mechanisms responsible for causing immune suppression are not completely understood. Macrophages and neutrophils generate reactive oxygen species (ROS)/reactive nitrogen species as a defense mechanism for the clearance of phagocytosed microorganisms. ROS serve a dual role; at high concentrations they act as microbicidal effector molecules that destroy intracellular pathogens, and at low concentrations they serve as secondary signaling messengers that regulate the expression of various inflammatory mediators. We hypothesized that the antioxidant defenses of F. tularensis maintain redox homeostasis in infected macrophages to prevent activation of redox-sensitive signaling components that ultimately result in suppression of pro-inflammatory cytokine production and macrophage microbicidal activity. We demonstrate that antioxidant enzymes of F. tularensis prevent the activation of redox-sensitive MAPK signaling components, NF-κB signaling, and the production of pro-inflammatory cytokines by inhibiting the accumulation of ROS in infected macrophages. We also report that F. tularensis inhibits ROS-dependent autophagy to promote its intramacrophage survival. Collectively, this study reveals novel pathogenic mechanisms adopted by F. tularensis to modulate macrophage innate immune functions to create an environment permissive for its intracellular survival and growth.

Genotipificación de Acinetobacter baumannii multi-resistente aislado en el hospital Dr. Domingo Luciani de caracas / Genotypification of multiresistant Acinetobacter baumannii isolated in the Dr. Domingo Luciani Hospital of caracas

Las técnicas de genotipificación tienen un rol fundamental en el estudio de las infecciones nosocomiales. Las infecciones nosocomiales son producidas principalmente por microorganismos que son resistentes a los antimicrobianos, que por lo general han sido seleccionados por el uso inadecuado de la terapia antimicrobiana. Entre las especies que causan frecuentemente este tipo de infecciones se encuentra A. baumannii multi-resistente. En esta investigación se planteó genotipificar mediante las técnicas ERIC-PCR y REP-PCR 19 cepas de A. baumannii multi-resistente aisladas en el hospital Dr. Domingo Luciani de Caracas. La confirmación molecular de la especie A. baumannii se realizó mediante la detección de la oxacilinasa OXA 51 por PCR, el 100% de los aislados incluidos en el estudio resultaron positivos para la detección del gen blaOXA-51-Like. La susceptibilidad antimicrobiana y la detección fenotípica de mecanismos de resistencia se efectuaron de acuerdo a las normas de la CLSI 2009. Se determinó policlonalidad en los 19 aislados de A. baumannii, con el predominio de cuatro clones en la Unidad de Terapia Intensiva de Adultos y el área de Hospitalización del Hospital Dr. Domingo Luciani de Caracas. La correlación de los datos epidemiológicos con las características de la resistencia y la información molecular de cada una de las muestras permitió identificar dos patrones de infección: infecciones de origen endógeno, las cuales se caracterizaron por la diversidad genética de los aislamientos, e infecciones cruzadas, debido al hallazgo de cepas estrechamente relacionadas en espacios cercano o distantes del centro de salud. Se demostró que ERIC-PCR y REP-PCR bajo las condiciones estandarizadas en este estudio son técnicas confiables desde el punto de vista de la estabilidad de los marcadores moleculares y la reproducibilidad para caracterizar brotes ocasionados por A. baumannii, considerándose la técnica REP-PCR más adecuada para estudios de genotipificación...

The genotypification techniques have a fundamental role in the study of nosocomial infections. These infections are produced principally by microorganisms that are antimicrobial resistant, that have benn selected by the inadequate use of antimicrobial therapy. Between the species that frequently cause these type of infections is the A baumannii multi-resistant. In this investigation we established to genotypificate by ERIC-PCR y REP-PCR techniques 19 strains of A baumannii multi-resitant isolated in the Dr. Domingo Luciani Hospital of Caracas. The molecular confirmation of the species was realized by the detection of the oxacilianse OXA 51 by PCR. 100% of the isolates included in the study resulted positive for the gen bla OXA-51-Like. The antimocrobial susceptibility and the phenotypic detection of resistance mechanism were done according the CLSI 2009 normative. We determined policlonality on the 19 isolates of A. baumannii, with the predominance of 4 clones in the Intensive Therapy unit and the hospitalization area of the hospital. The correlation of the epidemiological data with the resistance characteristics and the molecular information of each sample allowed us to identificate two patterns of infections: endogen origin infection, which was charaterized by the genetic diversity of the isolates and cross infections, due to the finding of strains closely related in spaces near o distant ffrom the health center. We demostrated that ERIC-PCR and REP-PCR under standarized conditions in this study are good techiques fron the point of view of the stability of the molecular markers and the reproducibility to characterize outbreaks occasioned by A. baumannii, consideratin the REP-PCR technique, the most adequate for genotypification of this strain.