Repurposing disulfiram, an alcohol-abuse drug, in neuroblastoma causes KAT2A downregulation and in vivo activity with a water/oil emulsion.

Neuroblastoma, the most common type of pediatric extracranial solid tumor, causes 10% of childhood cancer deaths. Despite intensive multimodal treatment, the outcomes of high-risk neuroblastoma remain poor. We urgently need to develop new therapies with safe long-term toxicity profiles for rapid testing in clinical trials. Drug repurposing is a promising approach to meet these needs. Here, we investigated disulfiram, a safe and successful chronic alcoholism treatment with known anticancer and epigenetic effects. Disulfiram efficiently induced cell cycle arrest and decreased the viability of six human neuroblastoma cell lines at half-maximal inhibitory concentrations up to 20 times lower than its peak clinical plasma level in patients treated for chronic alcoholism. Disulfiram shifted neuroblastoma transcriptome, decreasing MYCN levels and activating neuronal differentiation. Consistently, disulfiram significantly reduced the protein level of lysine acetyltransferase 2A (KAT2A), drastically reducing acetylation of its target residues on histone H3. To investigate disulfiram's anticancer effects in an in vivo model of high-risk neuroblastoma, we developed a disulfiram-loaded emulsion to deliver the highly liposoluble drug. Treatment with the emulsion significantly delayed neuroblastoma progression in mice. These results identify KAT2A as a novel target of disulfiram, which directly impacts neuroblastoma epigenetics and is a promising candidate for repurposing to treat pediatric neuroblastoma.

Evaluación del estado emocional de personas con diabetes mellitus en la práctica ambulatoria / Evaluation of the emotional state of people with diabetes mellitus in outpatient practice

La aparición de una enfermedad crónica, como la diabetes mellitus (DM), pone a prueba la respuesta del universo físico y psíquico de un individuo. Como objetivo general, se propone evaluar el estado emocional de las personas con DM en la consulta ambulatoria. Como objetivo particular, detectar y monitorear las necesidades psicológicas que deben formar parte integral del cuidado de la DM mediante el uso de métodos validados. El cuestionario WHO-5 se incluye como índice de bienestar general, el PAID-5 revela la existencia de una posible angustia emocional vinculada a la enfermedad, y el PHQ- 9 como índice de depresión. Ante esta situación, el Comité de Aspectos Psicosociales recomienda explorar estos aspectos para optimizar el control y el tratamiento de la enfermedad, proponiendo estas herramientas para que el equipo de salud las emplee en la detección y el reconocimiento del estado emocional de las personas con DM

Occurrence of a chronic disease, such as diabetes, prove the response of the physical and psychic universe of individuals. As a general objective, is proposed to evaluate emotional state of people with diabetes in the outpatient clinic. As principal objective, detection and monitoring the psychological needs should be a main part of diabetes care, using validated tools to evaluate this aspect. WHO-5 questionnaire is included as an index of general well-being, PAID-5, reveals the existence of a possible emotional distress linked to disease, and PHQ-9 is used as an index of depression. At this situation, the Committee on Psycho-Social Aspects recommends explore these psychological aspects, as a way to optimize the control and treatment of disease, and propose the cited tools, to be used by the health team, in detection and recognition of emotional state in people with diabetes.

Evaluación del estado emocional de personas con diabetes mellitus en la práctica ambulatoria / Evaluation of the emotional state of people with diabetes mellitus in outpatient practice

Resumen La aparición de una enfermedad crónica, como la diabetes mellitus (DM), pone a prueba la respuesta del universo físico y psíquico de un individuo. Como objetivo general, se propone evaluar el estado emocional de las personas con DM en la consulta ambulatoria. Como objetivo particular, detectar y monitorear las necesidades psicológicas que deben formar parte integral del cuidado de la DM mediante el uso de métodos validados. El cuestionario WHO-5 se incluye como índice de bienestar general, el PAID-5 revela la existencia de una posible angustia emocional vinculada a la enfermedad, y el PHQ-9 como índice de depresión. Ante esta situación, el Comité de Aspectos Psicosociales recomienda explorar estos aspectos para optimizar el control y el tratamiento de la enfermedad, proponiendo estas herramientas para que el equipo de salud las emplee en la detección y el reconocimiento del estado emocional de las personas con DM.

Abstract Occurrence of a chronic disease, such as diabetes, prove the response of the physical and psychic universe of individuals. As a general objective, is proposed to evaluate emotional state of people with diabetes in the outpatient clinic. As principal objective, detection and monitoring the psychological needs should be a main part of diabetes care, using validated tools to evaluate this aspect. WHO-5 questionnaire is included as an index of general well-being, PAID-5, reveals the existence of a possible emotional distress linked to disease, and PHQ-9 is used as an index of depression.

Evaluación de la funcionalidad del eje hipotálamo-hipófiso-adrenal a través del test de respuesta del cortisol al despertar en pacientes con diabetes mellitus tipo 1 con y sin depresión: Estudio Multicéntrico Argentino (EMA-1) / Evaluation of the hypothalamo-pituitary-adrenal axis using the cortisol awakening response test in patients with type 1 diabetes mellitus with and without depression: Multicenter Argentine Study (EMA-1)

Introducción: la depresión (DP) tiene una alta prevalencia en pacientes con diabetes mellitus tipo 1 (DM1) y se asocia a repercusiones clínicas negativas como mayor morbimortalidad cardiovascular y complicaciones crónicas. Existen pocos estudios publicados sobre la funcionalidad del eje hipotálamo-hipófiso-adrenal (H-H-A) en DM1 con DP, y la relación entre la DP y el test de respuesta del cortisol al despertar (RCD) con el control glucémico (CG). Objetivos: analizar la funcionalidad del eje H-H-A a través de la evaluación del RCD en pacientes con DM1 (PD1) con y sin DP. Como objetivos secundarios, conocer la prevalencia de DP en PD1 y ver si existe relación entre el RCD y CG, y entre DP y CG. Materiales y métodos: estudio observacional, prospectivo, de corte transversal, multicéntrico, nacional. Se incluyeron PD1 mayores de 18 años; se utilizó cuestionario Patient Health Questionnaire-9 (PHQ-9) para diagnóstico de DP. Se tomaron muestras de cortisol salival al despertar y a los 30 minutos (RCD), y se consideró RCD bloqueado si el valor de cortisol de los 30 minutos no aumentaba más del 50% del basal. Además se tomaron muestras de sangre en ayunas para medir glucemia, fructosamina y HbA1c. Resultados: se incluyeron 79 pacientes, 39% hombres, edad promedio 38±15 años, duración de la diabetes de 16±13 años; 53% casados/en pareja y 87% con ingresos económicos estables. El 68% de los PD1 presentó el RCD bloqueado. En PD1 con DP el 85% presentó el RCD bloqueado vs el 60% en los no deprimidos y dicha diferencia fue marginalmente significativa (p=0,05). La prevalencia de DP fue de 39%. No se encontró ninguna relación significativa entre RCD bloqueado y control glucémico (p>0,05). Los PD1 con DP moderada-severa presentaron un peor control glucémico en relación a los PD1 sin depresión (evaluado por glucemia mayor de 120 mg/dl, fructosamina mayor de 285 umol/l; p<0,05) y la relación no fue significativa para HbA1c aunque mostró una tendencia. Conclusiones: en pacientes con DM1 y DP se halló el RCD bloqueado en un alto porcentaje. Dado que la DP se asocia a mayor morbimortalidad cardiovascular, podría utilizarse el test de RCD como biomarcador de DP, y podría servir para estratificar esta sub-población de alto de riesgo. La depresión moderada-severa se asoció a peor control glucémico, por lo tanto, diagnosticar y tratar adecuadamente la DP en PD1 podría contribuir a prevenir la aparición o progresión de complicaciones crónicas.

Introduction: depression (DP) has a high prevalence in patients with type 1 diabetes mellitus (DM1) and is associated with negative clinicals consequences like more cardiovascular morbimortality and chronic complications. There are few studies published about the dysregulation of hypothalamopituitary-adrenal axis (H-P-A) in DM1 with DP and the relation between DP and the Cortisol Awakening Response Test (CAR) with the glycemic control (GC). Objectives: examine the functionality of the H-P-A axis using the Cortisol Awakening Response Test (CAR), in patients with DM1 (PD1) with and without DP. Determine the prevalence of DP in PD1 and examine if there is any relation between CAR and GC and DP and poorer GC. Materials and methods: observational, prospective, national, multicenter study. Patients with DM1, older than 18 years old; Patient Health-9 questionnaire (PHQ-9) was used to diagnose DP and 2 samples of salivary cortisol, and blood samples for glycemia, glycated albumin and Hba1c. Results: 79 patients with DM1 (PD1) were included, 39% male, mean age 38± 15 years old, an average of 16±13 years evolution of diabetes; 53 % married/couple and 87 % have a regular incomes. 68% of PD1 presented CAR blunted. In PD1 with DP 85% has CAR blunted versus 60% in those without DP, and this difference was marginally significant (p=0.05). The prevalence of DP was 39%. No significant relation was found between CAR blunted and glycemic control (p>0.05).PD1 with Moderate-severe DP showed worse metabolic control than the PD1 without DP (evaluated by glycemia higher than 120 mg/dl, glycated albumin higher than 285 umol/l); p<0.05) and the relation was not significant with HbA1c but it showed a trend. Conclusions: patients with DM1 and DP presented a high prevalence of CAR blunted. DP is related with higher cardiovascular morbi-mortality, thus CAR would be useful as a biomarker of DP and would be used to stratify this population of high risk. DP moderate-severe was related to worse glycemic control, hence diagnose and treat correctly DP in PD1 would contribute to prevent the onset or the evolution of chronic complications.

Articulación entre teoría y práctica desde aprendizaje significativo en el campo de enfermería / Articulation between theory and practice from meaningful learning in the nursing field

Introdución: mediante el aprendizaje los seres vivos adquieren conocimientos sobre el mundo que los rodea, debido a que ciertas áreas cerebrales son capaces de crear redes neuronales. El aprendizaje significativo parte de las experiencias adquiridas y los conocimientos previos, considerado como la forma más completa de aprender, por lo tanto, dentro del área de la salud se requiere problematizar los procesos educativos en la generación de aprendizajes significativos. Objetivo: describir la relación entre los cuidados de enfermería y la importancia de la educación continua entre el profesional mediante el aprendizaje significativo. Material y métodos: se realizó una búsqueda en bases de datos como EBSCO, PubMed y SciELO, las palabras clave empleadas fueron: aprendizaje significativo, conocimiento, enfermería y cuidados, en donde se encontrará la asociación del aprendizaje significativo con relación a los cuidados de enfermería. Conclusión: los cuidados de enfermería y la formación de los profesionales están mediados por la construcción de conocimientos con base a experiencias previas, es decir de lo que se ha aprendido a lo largo de su formación académica, lo cual le permite ejecutar un pensamiento crítico con un aprendizaje autodirigido.

Unified Scaling of the Structure and Loading of Nanoparticles Formed by Diffusion-Limited Coalescence.

The present study establishes the scaling laws describing the structure of spherical nanoparticles formed by diffusion-limited coalescence. We produced drug-loaded nanoparticles from a poly(ethylene glycol)-poly(d,l-lactic acid) diblock polymer (PEG- b-PLA) by the nanoprecipitation method using different types of micromixing chambers to explore multiple mixing regimes and characteristic times. We first show that the drug loading of the nanoparticles is not controlled by the mixing time but solely by the drug-to-polymer ratio (D:P) in the feed and the hydrophobicity of the drug scaled via the partition coefficient P. We then procure compelling evidence that particles formed via diffusion/coalescence exhibit a relative distribution of PEG blocks between the particle core and its shell that depends only on mixing conditions (not on D:P). Scaling laws of PEG relative distribution and chain surface density were derived in different mixing regimes and showed excellent agreement with experimental data. In particular, results made evident that PEG blocks entrapment in the core of the particles occurs in the slow-mixing regime and favors the overloading (above the thermodynamic limit) of the particles with hydrophilic drugs. The present analysis compiles effective guidelines for the scale up of nanoparticles structure and properties with mixing conditions, which should facilitate their future translation to medical and industrial settings.

Psychological the most common elder abuse in a Havana neighborhood.

INTRODUCTION: Globally, older adults are a population group that often suffers abuse by their caregivers. Along with women and children, they are among those most often reported as victims of abuse of any kind in Cuba. OBJECTIVE: Characterize presence of domestic abuse of older adults in family doctor-and-nurse office No. 28 of the Carlos Manuel Portuondo University Polyclinic in Havana, Cuba, determining the main manifestations of abuse and help-seeking behavior by the older adults identified as victims. METHOD: This was a descriptive cross-sectional study of adults aged ≥ 60 years; all those not diagnosed with dementia and who agreed to participate were interviewed. In a universe of 268 older adults, 29 were living outside the area, 24 declined to participate, and 18 had a diagnosis of dementia, leaving a study population of 197 individuals. Variables included: personal experience of abuse, type of abuse, perpetrator, help sought, and reasons for not seeking help. Statistical analysis was based on percentages. RESULTS: Of 197 older adults interviewed, 88 (44.7%) reported that they were victims of domestic abuse; 50 of these were women. The most common types of abuse were psychological abuse and disrespect for personal space, reported by 69 (78.4%) and 54 (61.4%) individuals, respectively. Sons- and daughters-in-law were identified as the abusers by 68 participants and grandchildren by 65. Of the 88 victims, 67 (76.1%) stated that they did not seek help. CONCLUSIONS: The finding that substantial numbers of older adults are victims of domestic abuse brings to light a hitherto insufficiently addressed issue in the community studied. More research is needed to deepen understanding of the scope and causes of the problem to inform prevention and management strategies, not only at the level of the polyclinic catchment area, but in the health system in general.