Niveles de burnout y de exposición a conflicto ético de los profesionales de enfermería de cuidados intensivos / Levels of burnout and exposure to ethical conflict and assessment of the practice environment in nursing professionals of intensive care

Introducción: Los profesionales de enfermería que trabajan en unidades de cuidados intensivos (UCI) poseen un alto riesgo de desarrollar respuestas emocionales negativas, así como problemas emocionales y espirituales relacionados con cuestiones éticas. El diseño de estrategias efectivas que mejoren estos aspectos viene determinado por el conocimiento de los niveles de burnout y conflicto ético de dichos profesionales, así como la influencia que el entorno de la práctica puede tener en ellos. Objetivo: Analizar la relación existente entre niveles de burnout, exposición a conflicto ético y la percepción del ambiente de la práctica entre sí y con las variables sociodemográficas de los diferentes profesionales de enfermería de cuidados intensivos. Metodología: Estudio transversal correlacional en una UCI de un hospital universitario de nivel terciario. Se evaluó el nivel de burnout con la escala Maslach Burnout Inventory-Human-Services Survey; el nivel de conflicto ético, con el cuestionario de conflictividad ética para enfermeros, y la percepción del entorno, con la escala Practice-Environment-Scale of the Nursing-Work-Index. La asociación entre variables categóricas ha sido analizada mediante el test exacto de Fisher de chi-cuadrado (χ2). Resultados: Se evaluaron 39 enfermeras y 8 auxiliares, obteniendo una tasa de participación del 82,93%. El 31,10% de los profesionales de enfermería presentaron signos de burnout, el 14,89% consideraron que trabajan en un entorno desfavorable y el 87,23% presentaron un índice de exposición a conflicto ético medio-alto.El nivel educativo (χ2=11,084, p=0,011) y la categoría profesional (χ2=5,007, p=0,025) influyeron en el nivel de burnout, presentando las auxiliares mayores niveles del mismo...(AU)

Background: Nursing professionals working in intensive care units (ICU) are at high risk of developing negative emotional responses as well as emotional and spiritual problems related to ethical issues. The design of effective strategies that improve these aspects is determined by knowing the levels of burnout and ethical conflict of these professionals, as well as the influence that the practice environment might have on them. Objectives: To analyze the relationship between levels of burnout, the exposure to ethical conflicts and the perception of the practice environment among themselves and with sociodemographic variables of the different intensive care nursing professionals. Methods: Descriptive, correlational, cross-sectional, observational study in an ICU of a tertiary level university hospital. The level of burnout was evaluated with the Maslach Burnout Inventory Human Services Survey scale; the level of ethical conflict with the Ethical Conflict Questionnaire for Nurses; and the perception of the environment with the Practice Environment Scale of the Nursing Work Index. Descriptive and inferential statistics were performed. The association between categorical variables was analyzed using Fisher's exact chi-square test (χ2). Results: 31 nurses and 8 nursing assistants were evaluated, which meant a participation rate of 82.93%. 31.10% of the nursing professionals presented signs of burnout, 14.89% considered that they work in an unfavorable environment and 87.23% presented a medium-high index of exposure to ethical conflict. The educational level (χ2=11.084, P=.011) and the professional category (χ2=5.007, P=.025) influenced the level of burnout: nursing assistants presented higher levels of this. When comparing the level of burnout with the environment and the index of ethical conflict, there were no statistically significant differences...(AU)

Levels of burnout and exposure to ethical conflict and assessment of the practice environment in nursing professionals of intensive care.

BACKGROUND: Nursing professionals working in Intensive Care Units (ICU) are at high risk of developing negative emotional responses as well as emotional and spiritual problems related to ethical issues. The design of effective strategies that improve these aspects is determined by knowing the levels of burnout and ethical conflict of these professionals, as well as the influence that the practice environment might have on them. OBJECTIVES: To analyze the relationship between levels of burnout, the exposure to ethical conflicts and the perception of the practice environment among themselves and with sociodemographic variables of the different intensive care nursing professionals. METHODS: Descriptive, correlational, cross-sectional, observational study in an ICU of a tertiary level university hospital. The level of burnout was evaluated with the Maslach Burnout Inventory Human Services Survey scale; the level of ethical conflict with the Ethical Conflict Questionnaire for Nurses and the perception of the environment with the Practice Environment Scale of the Nursing Work Index. Descriptive and inferential statistics were performed. The association between categorical variables was analyzed using Fisher's exact chi-square test (χ2) RESULTS: 31 nurses and 8 nursing assistants were evaluated, which meant a participation rate of 82,93%. 31,10% of the nursing professionals presented signs of burnout, 14,89% considered that they work in an unfavorable environment and 87,23% presented a medium-high index of exposure to ethical conflict. The educational level (χ2=11.084, p=0.011) and the professional category (χ2=5.007, p=0.025) influenced the level of burnout: nursing assistants presented higher levels of this. When comparing the level of burnout with the environment and the index of ethical conflict, there were no statistically significant differences. CONCLUSIONS: The absence of association found in the study between Burnout and ethical conflict with the perception of the practice environment suggests that personal factors may influence its development.

APOE3 Christchurch modulates tau phosphorylation and ß-catenin/Wnt/Cadherin signaling in induced pluripotent stem cell-derived cerebral organoids from Alzheimer's cases.

Alzheimer's disease (AD) is the most common cause of dementia among older adults. APOE3 Christchurch (R136S, APOE3Ch ) variant homozygosity was reported in an individual with extreme resistance to autosomal dominant AD due to the PSEN1 E280A mutation. This subject had a delayed clinical age at onset and resistance to tauopathy and neurodegeneration despite extremely high amyloid plaque burden. We established induced pluripotent stem (iPS) cell-derived cerebral organoids from this resistant case and from a non-protected kindred control (with PSEN1 E280A and APOE3/3 ). We used CRISPR/Cas9 gene editing to successfully remove the APOE3Ch to wild type in iPS cells from the protected case and to introduce the APOE3Ch as homozygote in iPS cells from the non-protected case to examine causality. We found significant reduction of tau phosphorylation (pTau 202/205 and pTau396) in cerebral organoids with the APOE3Ch variant, consistent with the strikingly reduced tau pathology found in the resistant case. We identified Cadherin and Wnt pathways as signaling mechanisms regulated by the APOE3Ch variant through single cell RNA sequencing in cerebral organoids. We also identified elevated ß-catenin protein, a regulator of tau phosphorylation, as a candidate mediator of APOE3Ch resistance to tauopathy. Our findings show that APOE3Ch is necessary and sufficient to confer resistance to tauopathy in an experimental ex-vivo model establishing a foundation for the development of novel, protected case-inspired therapeutics for tauopathies, including Alzheimer's.

TPEN selectively eliminates lymphoblastic B cells from bone marrow pediatric acute lymphoblastic leukemia patients.

B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic disorder characterized by the abnormal proliferation and accumulation of immature B-lymphoblasts arrested at various stages of differentiation. Despite advances in treatment, a significant percentage of pediatric patients with precursor B-ALL still relapse. Therefore, alternative therapies are needed to improve the cure rates for pediatric patients. TPEN (N, N, N', N'-tetrakis(2-pyridylmethyl)-ethylenediamine) is a pro-oxidant agent capable of selectively inducing apoptosis in leukemia cell lines. Consequently, it has been suggested that TPEN could be a potential agent for oxidative therapy. However, it is not yet known whether TPEN can selectively destroy leukemia cells in a more disease-like model, for example, the bloodstream and bone marrow (BM), ex vivo. This investigation is an extension of a previous study that dealt with the effect of TPEN on ex vivo isolated/purified refractory B-ALL cells. Here, we evaluated the effect of TPEN on whole BM from nonleukemic patients (control) or pediatric patients diagnosed with de novo B-ALL or refractory B-ALL cells by analyzing the hematopoietic cell lineage marker CD34/CD19. Although TPEN was innocuous to nonleukemic BM (n = 3), we found that TPEN significantly induced apoptosis in de novo (n = 5) and refractory B-ALL (n = 6) leukemic cell populations. Moreover, TPEN significantly increased the counts of cells positive for the oxidation of the stress sensor protein DJ-1, a sign of the formation of H2O2, and significantly increased the counts of cells positive for the pro-apoptotic proteins TP53, PUMA, and CASPASE-3 (CASP-3), indicative of apoptosis, in B-ALL cells. We demonstrate that TPEN selectively eliminates B-ALL cells (CD34 + /CD19 +) but no other cell populations in BM (CD34 + /CD19-; CD34-/CD19 + ; CD34-/CD19-) independent of age, diagnosis status (de novo or refractory), sex, karyotype, or immunophenotype. Understanding TPEN-induced cell death in leukemia cells provides insight into more effective therapeutic oxidation-inducing anticancer agents.