Targeting BPTF Sensitizes Pancreatic Ductal Adenocarcinoma to Chemotherapy by Repressing ABC-Transporters and Impairing Multidrug Resistance (MDR).

Pancreatic ductal adenocarcinoma (PDA) is characterized by an extremely poor prognosis due to its late diagnosis and strong chemoresistance to the current treatments. Therefore, finding new therapeutic targets is an urgent need nowadays. In this study, we report the role of the chromatin remodeler BPTF (Bromodomain PHD Finger Transcription Factor) as a therapeutic target in PDA. BPTF-silencing dramatically reduced cell proliferation and migration in vitro and in vivo in human and mouse PDA cell lines. Moreover, BPTF-silencing reduces the IC50 of gemcitabine in vitro and enhanced its therapeutic effect in vivo. Mechanistically, BPTF is required for c-MYC recruitment to the promoter of ABC-transporters and its downregulation facilitates gemcitabine accumulation in tumour cells, increases DNA damage, and a generates a strong synergistic effect in vivo. We show that BPTF is a therapeutic target in pancreatic ductal adenocarcinoma due to its strong effect on proliferation and in response to gemcitabine.

Percepciones de los profesionales de enfermería sobre los cuidados en el paciente geriátrico / Perceptions of Nursing professionals about care in the geriatric patient

Objetivos: Conocer y describir cómo perciben las enfermeras que trabajan con pacientes geriátricos los cuidados de enfermería proporcionados, los problemas con los que se encuentran, así como las soluciones para mejorarlos. Métodos: Estudio cualitativo de tipo fenomenológico basado en entrevistas semiestructuradas. La información obtenida se analizó mediante análisis de contenido y se verificó con la triangulación de los resultados. Resultados: Emergieron siete categorías coincidentes en todas las entrevistas realizadas: percepciones de las enfermeras sobre los cuidados de enfermería en el paciente geriátrico, calidad de los cuidados de enfermería, dificultades al proporcionar los cuidados de enfermería, propuestas de mejoras de enfermería, satisfacción del paciente y familia con la enfermera, presente y futuro de la profesión enfermera, y el trabajo de equipo. Las enfermeras consideran el cuidado como un arte y la esencia de la profesión; la persona enferma es la pieza clave que justifica la profesión. Conclusiones: os profesionales consideran que son fundamentales: el reconocimiento de las especialidades de enfermería, la formación continua, que las administraciones motiven a sus profesionales, prevenir el síndrome de estar quemado, enseñar a trabajar en equipo y avanzar hacia la seguridad del paciente y del profesional (AU)

Objectives: Objectives: to know and describe how nurses perceive the care they provide in the daily work with geriatric patients, the problems they find as well as the solutions to improve them. Methods: qualitative phenomenological study based on semi-structured interviews. The information obtained was analyzed by content analysis and verified with the triangulation of the results. Results: Seven matching categories emerged in all the conducted interviews: nurses perceptions about the care of geriatric patient, quality of nursing care, difficulties to apply nursing care, proposals for improvement of nursing, patient and family satisfaction with the nurse work, present and future of the nursing profession, and the teamwork. Nurses consider care as an art and the essence of the profession; the sick person is the key piece that justifies the profession. Conclusions: professionals believe that, are fundamental: the recognition of nursing specialties, continuous education and training, that the administrations to motivate their professionals, prevention of the burnt-out syndrome, teach to work as a team, and move towards patient and professional safety (AU)

Myc-Related Mitochondrial Activity as a Novel Target for Multiple Myeloma.

Mitochondria are involved in the development and acquisition of a malignant phenotype in hematological cancers. Recently, their role in the pathogenesis of multiple myeloma (MM) has been suggested to be therapeutically explored. MYC is a master regulator of b-cell malignancies such as multiple myeloma, and its activation is known to deregulate mitochondrial function. We investigated the impact of mitochondrial activity on the distinct entities of the disease and tested the efficacy of the mitochondrial inhibitor, tigecycline, to overcome MM proliferation. COXII expression, COX activity, mitochondrial mass, and mitochondrial membrane potential demonstrated a progressive increase of mitochondrial features as the disease progresses. In vitro and in vivo therapeutic targeting using the mitochondrial inhibitor tigecycline showed promising efficacy and cytotoxicity in monotherapy and combination with the MM frontline treatment bortezomib. Overall, our findings demonstrate how mitochondrial activity emerges in MM transformation and disease progression and the efficacy of therapies targeting these novel vulnerabilities.

Craniopharyngiomas: A clinicopathological and molecular study of 52 cases - Experience in the Complejo Hospitalario de Toledo and Hospital Universitario 12 de Octubre (Madrid).

Craniopharyngiomas (CPs) are histologically benign tumors that are associated with high levels of morbidity. Two clinicopathological variants - adamantinomatous (ACP) and papillary (PCP) - have been described. They differ in their molecular features, whereby activating mutations in BRAF (V600E) and CTNNB1 genes characterize PCP and ACP, respectively. Recently, both variants have been shown to express elevated PD-L1 protein expression, but ACP also exhibited tumor cell-intrinsic PD-1 expression. In this study we analyze these molecular alterations in 52 cases with a long follow-up and examine their associations with immunohistochemical and clinical characteristics. ACPs comprise 73.1% of cases, while 21.2% are PCPs. Aberrant nuclear immunoreactivity for ß-catenin was observed in all ACPs. BRAF p.V600E mutations were observed in 90.9% of PCPs. Only one ACP case featured both alterations. Both types of CP exhibited strong nuclear staining for p63 with diffuse and basal distribution. ACP and PCP consistently expressed PD-L1, most in a substantial percentage of tumor cells, with a distinctive spatial distribution of expression in each subtype; only ACP demonstrated PD-1 expression. There was no evidence of differences in clinical prognosis between ACPs and PCPs. The identification of hallmark molecular signatures in the two CP variants is useful for sub-categorization in routine histopathology reporting. It is also pertinent to personalized therapy and for the development of improved non-invasive therapeutic strategies in this disease.

"Puerta giratoria" a la situación sin hogar. Influencia de la salud, consumo de alcohol y padecimiento de sucesos vitales estresantes en el número de episodios en la situación sin hogar / The revolving door to homelessness. The influence of health, alcohol consumption and stressful life events on the number of episodes of homelessness

Objetivos: Analizar la incidencia de diferentes variables en el padecimiento de reiterados episodios en la situación sin hogar. Método: El trabajo se realizó a partir de los datos obtenidos de una muestra representativa de las personas en situación sin hogar en Madrid (España) (n=188). Resultados: El padecimiento de una enfermedad grave o crónica ejerce un efecto en la "puerta giratoria" a la situación sin hogar mediado por una percepción subjetiva muy negativa de la propia salud que, a su vez, se encuentra mediada por el padecimiento de alguna discapacidad. El consumo excesivo de alcohol ejerce un efecto en la "puerta giratoria" a la situación sin hogar mediado por el acceso a tratamiento por problemas derivados de dicho consumo. Padecer una enfermedad grave o crónica correlaciona con tener o haber tenido problemas derivados de un consumo excesivo de alcohol. El padecimiento de múltiples sucesos vitales estresantes ejerce un efecto directo en la "puerta giratoria" a la situación sin hogar. Conclusiones: Para prevenir la "puerta giratoria" a la situación sin hogar hay que eliminar las barreras que dificultan el acceso a los recursos normalizados de salud a las personas en exclusión social, a la vez que implementar programas continuados de apoyo para las personas sin hogar o en riesgo que incluyan prioritariamente cuestiones de salud

Objectives: To analyse the impact of different variables on repeated episodes of homelessness. Method: The study was conducted based on data obtained from a representative sample of homeless people in Madrid (Spain) (n=188). Results: Suffering from a serious or chronic illness has an effect on the revolving door to homelessness, which is mediated by a highly negative subjective perception of the individual's own health, which is in turn mediated by suffering from a disability. Excessive alcohol consumption has an effect on the revolving door to homelessness, mediated by access to treatment for problems caused by alcohol consumption. Suffering from a serious or chronic illness correlates with having problems caused by excessive alcohol consumption. Experiencing multiple stressful life events has a direct effect on the revolving door to homelessness. Conclusions: To prevent the revolving door to homelessness, it is necessary to remove the barriers that hinder access to normal health resources which are experienced by people suffering from social exclusion, while implementing on going support programmes for homeless people or those at risk of homelessness, which primarily deal with health issues

Alcohol, pobreza y exclusión social: Consumo de alcohol entre personas sin hogar y en riesgo de exclusión en Madrid / Alcohol, poverty and social exclusion: Alcohol consumption among the homeless and those at risk of social exclusion in Madrid

El trabajo analiza diferentes aspectos relativos al consumo de alcohol entre personas en situación de pobreza y/o exclusión social. La información se recogió a partir de una muestra representativa de las personas sin hogar en Madrid (n = 188) y una muestra de personas en riesgo de exclusión social (n = 164) equiparada en sexo, edad y procedencia (españoles vs. extranjeros). Los resultados obtenidos indican que las personas sin hogar presentan un mayor consumo de alcohol y han padecido más problemas derivados de dicho consumo que las personas en riesgo de exclusión. La mayoría de personas sin hogar que tuvieron problemas con el alcohol padecieron estos de forma previa a encontrarse en la situación sin hogar, manifestaron tener peor salud y haberse encontrado en un mayor número de ocasiones en la situación sin hogar. Pese al importante problema que supone el consumo de alcohol entre los entrevistados, tan sólo un pequeño porcentaje había accedido a programas de tratamiento para problemas derivados del consumo de esta sustancia

The work analyzes different aspects related to alcohol consumption among homeless people and people at risk of social exclusion. The data was gathered from a representative sample of homeless people in Madrid (n = 188) and a sample of people at risk of social exclusion (n = 164) matched in sex, age, and origin (Spaniards vs. foreigners). The results showed that homeless people present a greater consumption of alcohol and have experienced more problems derived from its consumption than people at risk of social exclusion. Most of the homeless people who had alcohol-related problems had had them prior to their homelessness, and they stated they had poorer health and had experienced a greater number of homelessness episodes. Despite the relevance of problems related to alcohol among our sample, only a small percentage of the sample had participated in treatment programs for alcohol consumption

Alcohol, poverty and social exclusion: Alcohol consumption among the homeless and those at risk of social exclusion in Madrid. / Alcohol, pobreza y exclusión social: Consumo de alcohol entre personas sin hogar y en riesgo de exclusión en Madrid.

The work analyzes different aspects related to alcohol consumption among homeless people and people at risk of social exclusion. The data was gathered from a representative sample of homeless people in Madrid (n = 188) and a sample of people at risk of social exclusion (n = 164) matched in sex, age, and origin (Spaniards vs. foreigners). The results showed that homeless people present a greater consumption of alcohol and have experienced more problems derived from its consumption than people at risk of social exclusion. Most of the homeless people who had alcohol-related problems had had them prior to their homelessness, and they stated they had poorer health and had experienced a greater number of homelessness episodes. Despite the relevance of problems related to alcohol among our sample, only a small percentage of the sample had participated in treatment programs for alcohol consumption.

El trabajo analiza diferentes aspectos relativos al consumo de alcohol entre personas en situación de pobreza y/o exclusión social. La información se recogió a partir de una muestra representativa de las personas sin hogar en Madrid (n = 188) y una muestra de personas en riesgo de exclusión social (n = 164) equiparada en sexo, edad y procedencia (españoles vs. extranjeros). Los resultados obtenidos indican que las personas sin hogar presentan un mayor consumo de alcohol y han padecido más problemas derivados de dicho consumo que las personas en riesgo de exclusión. La mayoría de personas sin hogar que tuvieron problemas con el alcohol padecieron estos de forma previa a encontrarse en la situación sin hogar, manifestaron tener peor salud y haberse encontrado en un mayor número de ocasiones en la situación sin hogar. Pese al importante problema que supone el consumo de alcohol entre los entrevistados, tan sólo un pequeño porcentaje había accedido a programas de tratamiento para problemas derivados del consumo de esta sustancia.

Proteomic analysis reveals heat shock protein 70 has a key role in polycythemia Vera.

JAK-STAT signaling through the JAK2V617F mutation is central to the pathogenesis of myeloproliferative neoplasms (MPN). However, other events could precede the JAK2 mutation. The aim of this study is to analyze the phenotypic divergence between polycytemia vera (PV) and essential thrombocytemia (ET) to find novel therapeutics targets by a proteomic and functional approach to identify alternative routes to JAK2 activation. Through 2D-DIGE and mass spectrometry of granulocyte protein from 20 MPN samples, showed differential expression of HSP70 in PV and ET besides other 60 proteins. Immunohistochemistry of 46 MPN bone marrow samples confirmed HSP70 expression. The median of positive granulocytes was 80% in PV (SD 35%) vs. 23% in ET (SD 34.25%). In an ex vivo model KNK437 was used as an inhibition model assay of HSP70, showed dose-dependent inhibition of cell growth and burst formation unit erythroid (BFU-E) in PV and ET, increased apoptosis in the erythroid lineage, and decreased pJAK2 signaling, as well as a specific siRNA for HSP70. These data suggest a key role for HSP70 in proliferation and survival of the erythroid lineage in PV, and may represent a potential therapeutic target in MPN, especially in PV.

A new manual retinal thickness measurement protocol to evaluate high myopia patients.

PURPOSE: To validate a manual measurement protocol for quantifying retinal thickness (RT) using an optical coherence tomography (OCT) device in pathologic myopia patients. METHODS: The macular Cross Hair protocol of Stratus OCT3 (Carl Zeiss Meditec, Inc., Dublin, Calif., USA) was applied and manual RT gauging was performed using the caliper tool. Foveal and paramacular RT, located at 1 and 2 mm distances from the fovea in both vertical and horizontal scans, were measured. Three consecutive RT measurements were taken to assess measurement reliability. The within-subject coefficient of variation (CVw) and intraclass correlation coefficients (ICC) were calculated to validate the manual method. RESULTS: The mean axial length of the 29 eyes assessed was 28.28 ± 2.72 mm and the mean spherical refraction was -13.61 ± 6.68 diopters. CVw ranged from 0.86 to 8.73% and ICC varied from 0.81 to 0.98. CONCLUSION: A manual RT measurement protocol could reliably be used in the daily clinic for assessing pathologic myopic patients when OCT software segmentation fails.

Oxigenoterapia de alto flujo mediante cánula nasal en urgencias pediátricas / High flow oxygen by nasal cannula in paediatric emergencies

La incorporación al servicio de urgencias pediátricas del sistema de administración de oxigenoterapia a alto flujo no invasivo ha demostrado su eficacia en el tratamiento de patologías respiratorias pediátricas, frente a los métodos tradicionales como los dispositivos de presión positiva continua (CPAP) o los sistemas de oxigenoterapia convencionales, como las gafas nasales. El sistema Vapotherm® abre la puerta a la posibilidad del control y tratamiento de patologías respiratorias en el niño que anteriormente precisaban de traslado a un servicio de cuidados críticos pediátricos. La puesta en marcha del nuevo sistema en el hospital donde trabajan los autores de este artículo hizo que se revisaran los procedimientos de actuación para los profesionales de Enfermería del citado servicio de urgencias pediátricas. El objetivo del presente trabajo es dar a conocer estos nuevos métodos que han supuesto la necesidad de creación y puesta en marcha de protocolos y programas de formación para los profesionales, permitiendo el desarrollo de nuevas competencias para mejorar la calidad científica y técnica de los cuidados enfermeros en las urgencias pediátricas (AU)

Benign fleck retinal findings on multifocal ERG, microperimetry, and OCT.

A middle-aged asymptomatic woman presented with multiple yellow-white flecks in the retinal pigment epithelium (RPE) affecting both fundi in a symmetrical pattern. The lesions were distributed around the posterior pole and midperiphery but sparing the macula, a picture similar to what was defined by Gass as benign fleck retina. Visual acuity, visual fields, full-field electroretinogram, electrooculogram, and dark adaptation were normal. Multifocal electroretinogram [0] (mfERG) was slightly subnormal in the isopters 17° to 20°. In this same area, microperimetry confirmed a mild decrease in sensitivity more patent in the upper temporal sector where some hypoautofluorescent spots were detected. Optical coherence tomography (OCT) obtained through the flecks revealed a small increase in the thickness of the RPE. Autofluorescence showed increased autofluorescence within the flecks. OCT confirmed the anatomical location of the defect, whereas mfERG and microperimetry demonstrated for the first time that benign fleck retina can entail a functional defect.

[SUGAR: a self-test to unfold glucose-affection educational requirements]. / SUGAR: Un instrumento para priorizar la educación diabetológica.

To obtain a valid, reliable, stable and easy to use questionnaire to be used by professionals non-trained in diabetes education that allowed them to decide priority for diabetical education to a diabetic patient. The initial aim of the study is considered to have been achieved.

Sugar. Un instrumento para priorizar la educación diabetológica / Sugar: a self-test to unfold glucose-afection educational requirements

Se presenta un cuestionario válido, fiable, reproducible y fácil de emplear que permita priorizar la necesidad de educación diabetológica de una persona con diabetes por personal no especializado en este área de la atención sanitaria. SUGAR permite asignar prioridad en la necesidad de recibir educación diabetológica a una persona con diabetes de forma válida, fiable, estable y sencilla, a personal sanitario no especializado en esta actividad. Estudio financiado con la beca 83/98 de la Fundación Canaria de Investigación en Salud

To obtain a valid, reliable, stable and easy to use questionnaire to be used by professionals non-trained in diabetes education that allowed them to decide priority for diabetical education to a diabetic patient. The initial aim of the study is considered to have been achieved