RND3 Potentiates Proinflammatory Activation through NOTCH Signaling in Activated Macrophages.

Macrophage activation is a complex process with multiple control elements that ensures an adequate response to the aggressor pathogens and, on the other hand, avoids an excess of inflammatory activity that could cause tissue damage. In this study, we have identified RND3, a small GTP-binding protein, as a new element in the complex signaling process that leads to macrophage activation. We show that RND3 expression is transiently induced in macrophages activated through Toll receptors and potentiated by IFN-γ. We also demonstrate that RND3 increases NOTCH signaling in macrophages by favoring NOTCH1 expression and its nuclear activity; however, Rnd3 expression seems to be inhibited by NOTCH signaling, setting up a negative regulatory feedback loop. Moreover, increased RND3 protein levels seem to potentiate NFκB and STAT1 transcriptional activity resulting in increased expression of proinflammatory genes, such as Tnf-α, Irf-1, or Cxcl-10. Altogether, our results indicate that RND3 seems to be a new regulatory element which could control the activation of macrophages, able to fine tune the inflammatory response through NOTCH.

NOTCH4 potentiates the IL-13 induced genetic program in M2 alternative macrophages through the AP1 and IRF4-JMJD3 axis.

IL-13 signaling polarizes macrophages to an M2 alternatively activated phenotype, which regulates tissue repair and anti-inflammatory responses. However, an excessive activation of this pathway leads to severe pathologies, such as allergic airway inflammation and asthma. In this work, we identified NOTCH4 receptor as an important modulator of M2 macrophage activation. We show that the expression of NOTCH4 is induced by IL-13, mediated by Janus kinases and AP1 activity, probably mediated by the IL-13Rα1 and IL-13Rα2 signaling pathway. Furthermore, we demonstrate an important role for NOTCH4 signaling in the IL-13 induced gene expression program in macrophages, including various genes that contribute to pathogenesis of the airways in asthma, such as ARG1, YM1, CCL24, IL-10, or CD-163. We also demonstrate that NOTCH4 signaling modulates IL-13-induced gene expression by increasing IRF4 activity, mediated, at least in part, by the expression of the histone H3K27me3 demethylase JMJD3, and by increasing AP1-dependent transcription. In summary, our results provide evidence for an important role of NOTCH4 signaling in alternative activation of macrophages by IL-13 and suggest that NOTCH4 may contribute to the increased severity of lesions in M2 inflammatory responses, such as allergic asthma, which points to NOTCH4 as a potential new target for the treatment of these pathologies.

Impacto de la ecografía clínica en pacientes con insuficiencia cardíaca atendidos en hospitalización a domicilio / Impact of clinical ultrasound in patients with heart failure treated in home

Antecedentes y objetivo: En España, más del 10% de los pacientes con insuficiencia cardíaca aguda (ICA) dados de alta son reingresados en los primeros 30 días. Se diseña este trabajo para valorar si el tratamiento dela ICA guiado por ecografía clínica (EC) en el ámbito de hospitalización a domicilio (HAD) reduce la incidencia de reingreso y mortalidad respecto al abordaje estándar (AE).Pacientes y métodosSe diseñó un ensayo clínico aleatorizado (ECA), abierto, paralelo, unicéntrico y controlado (NT05042752). Se incluyeron de forma consecutiva a pacientes>18 años ingresados por ICA en HAD desde enero del 2021 hasta abril del 2021 en el Hospital Reina Sofía de Tudela. Los pacientes se aleatorizaron a «grupo ecografía (GE)» (realización de AE y EC) y «grupo control (GC)» (AE). El tratamiento diurético fue modificado según los hallazgos del AE junto con la EC o según los hallazgos del AE, respectivamente. Las variables principales fueron el riesgo relativo (RR) de reingreso y mortalidad por ICA.ResultadosUn total de 79 pacientes fueron aleatorizados, 39 a GE y 40 a GC. De ellos, solo completaron la intervención 35 del GC y 35 del GE. El riesgo de reingreso por ICA se redujo un 60% en el GE respecto del GC (RR 0,4; IC del 95%: 0,1-1) y el de mortalidad en un 30% (RR 0,7; IC del 95%: 0,2-2,2). A pesar de la relevante magnitud del efecto encontrado, los resultados no alcanzan la significación estadística por falta de potencia.ConclusiónNuestros resultados sugieren que en HAD, el tratamiento de la ICA guiado por EC podría reducir el riesgo de reingreso y mortalidad respecto al AE, aunque hacen falta estudios con mayor potencia estadística que confirmen estos resultados. (AU)

Background and objective: In Spain, more than 10% of patients discharged with acute heart failure (AHF) are readmitted in the first 30 days. This study is designed to assess whether the treatment of AHF guided by clinical ultrasound (CU) in the setting of hospitalization at home (HAH) reduces the incidence of readmission and mortality compared to the standard care (SC).Patients and methodsA randomized, open, parallel, single-center and controlled clinical trial (RCT) was designed (NT05042752). Patients >18 years of age admitted for AHF to HAD from January 2021 to April 2021 at the Reina Sofía Hospital in Tudela were consecutively included. The patients were randomized to the UG-ultrasound group (SC and CU performed) and the CG-control group (SC). The diuretic treatment was tailored according to the findings of the SC together with the CU or according to the findings of the SC respectively. The main variables were the relative risk of readmission and mortality from AHF.ResultsA total of 79 patients were randomized, 39 to UG and 40 to CG. Of these, only 35 of the UG and 35 of the CG completed the intervention. The risk of readmission due to AHF was reduced by 60% in UG compared to CG (RR 0.4; 95% CI: 0.1–1) and mortality by 30% (RR 0.7; 95% CI: 0.2–2.2). Despite the relevant magnitude of the effect found, the results did not reach statistical significance due to lack of power.ConclusionOur results suggest that in HAH, a CE guided strategy for AHF could reduce the risk of readmission and mortality compared to SC alone. However, studies with greater statistical power are needed to confirm these results. (AU)

Covid-19 y brotes laborales en la Comunidad de Madrid / Covid-19 outbreaks in the workplace in the autonomous Community of Madrid (CM)

Introducción: En el control de la COVID-19 en el ámbito laboral, ha sido imprescindible la colaboración de empresas y servicios prevención riesgos laborales con Salud Pública. Material y Métodos: Descriptivo de brotes laborales en la Comunidad de Madrid (julio 2020 - noviembre 2021). Variables: actividad económica de empresa y centro de trabajo, nº casos, y momento epidémico. Se catalogan algunos según comportamiento epidémico observado en determinadas actividades. Resultados: Se estudiaron 993 brotes laborales. Las actividades con más brotes: sanitaria y servicios sociales, comercio y reparación de vehículos de motor, y hostelería. Por centro laboral, las oficinas fueron las más afectadas. Se describieron seis tipos de brotes por su especificidad, recogiéndose las medidas más efectivas. Conclusiones: Las características de los brotes laborales covid-19 dependen de la actividad desarrollada y condiciones de trabajo, y exigen medidas preventivas específicas. El conocimiento aprendido durante la pandemia ha supuesto un mejor control de los mismos. (AU)

Introduction: The collaboration between companies and occupational health services with the public health administration service has played an important role to control COVID-19 in the workplace. Material and Method: Descriptive study of covid-19 outbreaks in workplace in CM (July 2020 - November 2021). Variables: economic activity of the company and workplace, number of cases, and epidemic period. Some of them are classified according to the specific epidemic behavior observed. Results: 993 outbreaks were studied. The activities with the highest number of outbreaks: were health and social services, trade and repair of motor vehicles, and hospitality. Among workplaces, offices were the most affected ones. Six types of outbreaks were described due to their specificity, and their most effective measures were collected. Conclusions: The characteristics of these outbreaks depend on the activities carried out and the working conditions, and require specific preventive measures. Knowledge acquired has provided better control of them. (AU)

Impact of clinical ultrasound in patients with heart failure treated in home. / Impacto de la ecografía clínica en pacientes con insuficiencia cardíaca atendidos en hospitalización a domicilio.

BACKGROUND AND OBJECTIVE: In Spain, more than 10% of patients discharged with acute heart failure (AHF) are readmitted in the first 30 days. This study is designed to assess whether the treatment of AHF guided by clinical ultrasound (CU) in the setting of hospitalization at home (HAH) reduces the incidence of readmission and mortality compared to the standard care (SC). PATIENTS AND METHODS: A randomized, open, parallel, single-center and controlled clinical trial (RCT) was designed (NT05042752). Patients >18 years of age admitted for AHF to HAD from January 2021 to April 2021 at the Reina Sofía Hospital in Tudela were consecutively included. The patients were randomized to the UG-ultrasound group (SC and CU performed) and the CG-control group (SC). The diuretic treatment was tailored according to the findings of the SC together with the CU or according to the findings of the SC respectively. The main variables were the relative risk of readmission and mortality from AHF. RESULTS: A total of 79 patients were randomized, 39 to UG and 40 to CG. Of these, only 35 of the UG and 35 of the CG completed the intervention. The risk of readmission due to AHF was reduced by 60% in UG compared to CG (RR 0.4; 95% CI: 0.1-1) and mortality by 30% (RR 0.7; 95% CI: 0.2-2.2). Despite the relevant magnitude of the effect found, the results did not reach statistical significance due to lack of power. CONCLUSION: Our results suggest that in HAH, a CE guided strategy for AHF could reduce the risk of readmission and mortality compared to SC alone. However, studies with greater statistical power are needed to confirm these results.

Different Expression Levels of DLK2 Inhibit NOTCH Signaling and Inversely Modulate MDA-MB-231 Breast Cancer Tumor Growth In Vivo.

NOTCH signaling is implicated in the development of breast cancer tumors. DLK2, a non-canonical inhibitor of NOTCH signaling, was previously shown to be involved in skin and breast cancer. In this work, we studied whether different levels of DLK2 expression influenced the breast cancer characteristics of MDA-MB-231 cells. We found that DLK2 overexpression inhibited NOTCH activation in a dose-dependent manner. Moreover, depending on the level of inhibition of NOTCH1 activation generated by different levels of DLK2 expression, cell proliferation, cell cycle dynamics, cell apoptosis, cell migration, and tumor growth in vivo were affected in opposite directions. Low levels of DLK2 expression produced a slight inhibition of NOTCH1 activation, and enhanced MDA-MB-231 cell invasion in vitro and cell proliferation both in vitro and in vivo. In contrast, MDA-MB-231 cells expressing elevated levels of DLK2 showed a strong inhibition of NOTCH1 activation, decreased cell proliferation, increased cell apoptosis, and were unable to generate tumors in vivo. In addition, DLK2 expression levels also affected some members of other cell signaling pathways implicated in cancer, such as ERK1/2 MAPK, AKT, and rpS6 kinases. Our data support an important role of DLK2 as a protein that can finely regulate NOTCH signaling and affect the tumor properties and growth dynamics of MDA-MB-231 breast cancer cells.

[Contribution of the occupational health to the COVID-19 pandemic control.] / Contribución de la salud laboral al control de la pandemia por covid-19 en España.

When the World Health Organization declared Covid-19 as a public health emergency of international concern, the Spanish Ministry of Health called the health, labor, social security authorities, Labor and Social Security Inspection, National Institute of Security and Occupational Health, employers, unions, occupational risk prevention services, mutual societies and scientific societies of occupational medicine and nursing, to collaborate in the control of the transmission of SARS-CoV-2 in companies. The Occupational Health Group of the Public Health Commission of the Interterritorial Council of the National Health System, developed the Procedure for the prevention of occupational risks in the face of exposure to SARS-CoV-2, which has been updated 15 times until the date. It contains the prevention measures to be implemented in the workplaces: organizational and collective protection, personal protection, especially vulnerable worker and risk level, study and management of cases and contacts that occurred in the company, collaboration in the management of temporary disability and, more recently, reincorporation and management of vaccinated workers. As a result of these cooperation and collaboration frameworks, a series of activities were deployed in the workplace, which are described in this article.

Cuando la Organización Mundial de la Salud declaró la Covid-19 como una emergencia de salud pública de importancia internacional, el Ministerio de Sanidad convocó a las autoridades sanitarias, laborales, de seguridad social, Inspección de Trabajo y Seguridad Social, Instituto Nacional de Seguridad y Salud en el Trabajo, empresarios, sindicatos, servicios de prevención de riesgos laborales, mutuas y sociedades científicas de la medicina y enfermería del trabajo, para colaborar en el control de la transmisión del SARS-CoV-2 en el ámbito de las empresas. La Ponencia de Salud Laboral de la Comisión de Salud Pública del Consejo Interterritorial del Sistema Nacional de Salud, elaboró el Procedimiento para los servicios de prevención de riesgos laborales frente a la exposición al SARS-CoV-2, que se ha actualizado 15 veces hasta la fecha. En él se recogen las medidas de prevención a implantar en los centros de trabajo: de carácter organizativo y de protección colectiva, de protección personal, de trabajador especialmente vulnerable y nivel de riesgo, de estudio y manejo de casos y contactos ocurridos en la empresa, de colaboración en la gestión de la incapacidad temporal y, más recientemente, de reincorporación y gestión de las y los trabajadores vacunados. Como resultado de esos marcos de cooperación y colaboración se desplegaron una serie de actividades en los lugares de trabajo que son descritas en este artículo.

NOTCH Receptors and DLK Proteins Enhance Brown Adipogenesis in Mesenchymal C3H10T1/2 Cells.

The NOTCH family of receptors and ligands is involved in numerous cell differentiation processes, including adipogenesis. We recently showed that overexpression of each of the four NOTCH receptors in 3T3-L1 preadipocytes enhances adipogenesis and modulates the acquisition of the mature adipocyte phenotype. We also revealed that DLK proteins modulate the adipogenesis of 3T3-L1 preadipocytes and mesenchymal C3H10T1/2 cells in an opposite way, despite their function as non-canonical inhibitory ligands of NOTCH receptors. In this work, we used multipotent C3H10T1/2 cells as an adipogenic model. We used standard adipogenic procedures and analyzed different parameters by using quantitative-polymerase chain reaction (qPCR), quantitative reverse transcription-polymerase chain reaction (qRT-PCR), luciferase, Western blot, and metabolic assays. We revealed that C3H10T1/2 multipotent cells show higher levels of NOTCH receptors expression and activity and lower Dlk gene expression levels than 3T3-L1 preadipocytes. We found that the overexpression of NOTCH receptors enhanced C3H10T1/2 adipogenesis levels, and the overexpression of NOTCH receptors and DLK (DELTA-like homolog) proteins modulated the conversion of cells towards a brown-like adipocyte phenotype. These and our prior results with 3T3-L1 preadipocytes strengthen the idea that, depending on the cellular context, a precise and highly regulated level of global NOTCH signaling is necessary to allow adipogenesis and determine the mature adipocyte phenotype.

Higher prevalence of psoriatic arthritis in the adult population in Spain? A population-based cross-sectional study.

OBJECTIVE: The prevalence of psoriatic arthritis (PsA) is very heterogeneous. There are no data on its frequency in the general population in Spain. The aim of EPISER2016 study was to estimate the prevalence of PsA in people aged ≥20 years in Spain. METHODS: Cross-sectional multicenter population-based study. Subjects from all the autonomous communities in Spain were randomly selected using multistage stratified cluster sampling. Participants in each of the municipalities randomly selected for the study were administered a telephone-based questionnaire to screen for the study diseases. If the participant reported being previously diagnosed, rheumatologists from the participant's reference hospital confirmed the diagnosis based on a review of the clinical history. Subjects not previously diagnosed but whose screening result was positive based on symptoms received a second telephone call from the investigating rheumatologist in order to evaluate the suspicion. If the suspicion remained, an appointment was made at the reference hospital to complete the diagnostic confirmation process according to CASPAR criteria. To calculate the prevalence and its 95% confidence interval (CI), the sample design was taken into account and weighing was calculated considering age, sex and geographic origin. RESULTS: The sample comprised 4916 subjects. The prevalence of PsA was 0.58% (95%CI: 0.38-0.87). All but 1 of the 27 cases (96.30%) had been diagnosed prior to EPISER2016. CONCLUSION: The prevalence of PsA in Spain was among the highest reported to date, only below that reported in Norway (0.67%) and slightly higher than that reported in Italy (0.42%).

Microbiological diagnosis in febrile neutropenia secondary to chemotherapy for hematologicmalignancy. A cohort description / Diagnóstico microbiológico en neutropenia febril secundaria a quimioterapia por malignidad hematológica Descripción de una cohorte

Abstract Objective: to describe the demographic, clinical, therapeutic and microbiological characteristics of patients with hematological malignancies undergoing chemotherapy who develop febrile neutropenia during treatment, as well as the mortality at discharge. Methods: a retrospective cohort study of patients with hematologic neoplasms who developed febrile neutropenia and were seen at the Hospital Universitario San Vicente Fundación in Medellín. Results: records of 110 episodes of febrile neutropenia were obtained. The mean age was 45 years. In 55.4%, a microbiological diagnosis was obtained; bacteremia was documented in 83.8% of these. The most common microorganisms wereK.pneumoniae(30%) andE. coli(18%). Antibiotic resistance due to ESBLs or carbapenemases ingram negativebacilli was 33%. Death occurred in 17% of patients. Acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML) were the most prevalent underlying diagnoses; the most prevalent clinical focus was bacteremia (24.5%). Conclusion: in our case series, there are significant differences in the percentage of patients with bacteremia, as well as in global mortality, compared to the rest of the cohorts in the region. A new research study needs to be carried out to clarify the source of these differences.(Acta Med Colomb 2020; 45. DOI:https://doi.org/10.36104/amc.2020.1386).

Resumen Objetivo: describir las características demográficas, clínicas, terapéuticas y microbiológicas de los pacientes con malignidad hematológica en quimioterapia que desarrollan neutropenia febril durante el tratamiento, así como la mortalidad al egreso. Métodos: estudio de cohorte retrospectivo en pacientes con neoplasia hematológica que desarrollaron neutropenia febril evaluados en el Hospital Universitario San Vicente Fundación de Medellín. Resultados: se obtuvo el registro de 110 episodios de neutropenia febril. Media de edad 45 años. En 55.4% se obtuvo diagnóstico microbiológico, la bacteriemia fue documentada en 83.8% de ellos. Los microorganismos más comunes fueronK.pneumoniae(30%) yE. coli(18%). La resistencia a antibióticos por presencia de BLEE o carbapenemasas en bacilosgram negativosfue de 33%. La mortalidad ocurrió en 17% de los pacientes. La leucemia linfoide aguda (LLA) y leucemia mieloide aguda (LMA) fueron los diagnósticos de base más prevalentes, el foco clínico más prevalente fue bacteriemia (24.5%). Conclusión: en nuestra cohorte se encontró diferencias significativas en cuanto al porcentaje de pacientes con bacteriemia, así como en la mortalidad global respecto al resto de cohortes de la región, es necesario desarrollar un nuevo trabajo de investigación que permita aclarar el origen de estas diferencias.(Acta Med Colomb 2020; 45. DOI:https://doi.org/10.36104/amc.2020.1386).

A vueltas con los registros: el valor de la comunicación de la sospecha de enfermedad profesional en la prevención de daños / Once again going about records: the value of communication of the suspicion of professional disease to prevent harms

No disponible

Voluntariado y cooperación en estudiantes universitarios del Grado de Medicina. Estudio observacional mediante cuestionario / Volunteering and cooperation among medical students. An observational questionnaire study

No disponible

Prevalencia de enfermedades reumáticas en población adulta en España (estudio EPISER 2016). Objetivos y metodología / Prevalence of rheumatic diseases in adult population in Spain (EPISER 2016 study): Aims and methodology

Objetivos: Describir la metodología del estudio de prevalencia de las enfermedades reumáticas en la población adulta en España, EPISER 2016, así como sus fortalezas y limitaciones. El objetivo del proyecto es estimar la prevalencia de artritis reumatoide (AR), artropatía psoriásica (APs), espondilitis anquilosante (EA), lupus eritematoso sistémico (LES), síndrome de Sjögren (SS), artrosis (de rodilla, cadera, manos, columna cervical y lumbar), fibromialgia, gota y fractura osteoporótica clínica. Material y método: Estudio transversal multicéntrico de base poblacional en el que participan 45 municipios de las 17 comunidades autónomas. La población de referencia está compuesta por adultos de 20 o más años residentes en España. La recogida de información se llevará a cabo mediante encuesta telefónica empleando el sistema Computer Assisted Telephone Interview (CATI). Las sospechas diagnósticas y los diagnósticos autorreferidos serán estudiadas por reumatólogos del hospital de referencia de los municipios seleccionados. Análisis estadístico: se calcularán las prevalencias de enfermedades reumáticas mediante estimadores y sus IC del 95%. Se calcularán factores de ponderación en función de la probabilidad de selección en cada una de las etapas del muestreo. Se tendrá en cuenta la distribución de la población en España según datos del Instituto Nacional de Estadística. Conclusiones: Los cambios sociodemográficos y en hábitos de vida durante los últimos 16 años justifican la realización de EPISER 2016. El estudio ofrecerá datos actualizados de prevalencia en AR, EA, APs, LES, SS, artrosis, fibromialgia, gota y fractura osteoporótica clínica. Los resultados permitirán comparar los datos con estudios de otros países y con el EPISER 2000

Aims: To describe the methodology of the EPISER 2016 (study of the prevalence of rheumatic diseases in adult population in Spain), as well its strengths and limitations. The aim of this study is to estimate the prevalence of rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), osteoarthritis (knee, hip, hands, and cervical and lumbar spine), fibromyalgia, gout and clinical osteoporotic fracture. Material and method: Population-based, multicenter, cross-sectional study, with the participation of 45 municipalities in the 17 Spanish autonomous communities. The reference population will consist of adults aged 20 years and over residing in Spain. A computer-assisted telephone interview (CATI) system will be used for data collection. Diagnostic suspicions and diagnoses received by the participants will be studied by rheumatologists in the referral hospitals in the selected municipalities. Statistical analysis: the prevalence of the rheumatic diseases will be calculated using estimators and their 95% confidence intervals. Weights will be calculated in each of the sampling stages in accordance with the probability of selection. The distribution of the population in Spain will be obtained from the Spanish Statistics Institute. Conclusions: Sociodemographic and lifestyle changes over the last 16 years justify EPISER 2016. This study will provide current data about the prevalences of RA, AS, PsA, SLE, SS, osteoarthritis, fibromyalgia, gout and clinical osteoporotic fracture. The results will allow comparisons with studies from other countries and EPISER 2000

Prevalence of rheumatic diseases in adult population in Spain (EPISER 2016 study): Aims and methodology. / Prevalencia de enfermedades reumáticas en población adulta en España (estudio EPISER 2016). Objetivos y metodología.

AIMS: To describe the methodology of the EPISER 2016 (study of the prevalence of rheumatic diseases in adult population in Spain), as well its strengths and limitations. The aim of this study is to estimate the prevalence of rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), osteoarthritis (knee, hip, hands, and cervical and lumbar spine), fibromyalgia, gout and clinical osteoporotic fracture. MATERIAL AND METHOD: Population-based, multicenter, cross-sectional study, with the participation of 45 municipalities in the 17 Spanish autonomous communities. The reference population will consist of adults aged 20 years and over residing in Spain. A computer-assisted telephone interview (CATI) system will be used for data collection. Diagnostic suspicions and diagnoses received by the participants will be studied by rheumatologists in the referral hospitals in the selected municipalities. STATISTICAL ANALYSIS: the prevalence of the rheumatic diseases will be calculated using estimators and their 95% confidence intervals. Weights will be calculated in each of the sampling stages in accordance with the probability of selection. The distribution of the population in Spain will be obtained from the Spanish Statistics Institute. CONCLUSIONS: Sociodemographic and lifestyle changes over the last 16 years justify EPISER 2016. This study will provide current data about the prevalences of RA, AS, PsA, SLE, SS, osteoarthritis, fibromyalgia, gout and clinical osteoporotic fracture. The results will allow comparisons with studies from other countries and EPISER 2000.

Author Correction: DLK proteins modulate NOTCH signaling to influence a brown or white 3T3-L1 adipocyte fate.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

DLK proteins modulate NOTCH signaling to influence a brown or white 3T3-L1 adipocyte fate.

The role of NOTCH signaling in adipogenesis is highly controversial, with data indicating null, positive or negative effects on this differentiation process. We hypothesize that these contradictory results could be due to the different global NOTCH signaling levels obtained in different experimental settings, because of a specific modulation of NOTCH receptors' activity by their ligands. We have previously demonstrated that DLK1 and DLK2, two non-canonical NOTCH1 ligands that inhibit NOTCH1 signaling in a dose-dependent manner, modulate the adipogenesis process of 3T3-L1 preadipocytes. In this work, we show that over-expression of any of the four NOTCH receptors enhanced adipogenesis of 3T3-L1 preadipocytes. We also determine that DLK proteins inhibit not only the activity of NOTCH1, but also the activity of NOTCH2, 3 and 4 receptors to different degrees. Interestingly, we have observed, by different approaches, that NOTCH1 over-expression seems to stimulate the differentiation of 3T3-L1 cells towards a brown-like adipocyte phenotype, whereas cells over-expressing NOTCH2, 3 or 4 receptors or DLK proteins would rather differentiate towards a white-like adipocyte phenotype. Finally, our data also demonstrate a complex feed-back mechanism involving Notch and Dlk genes in the regulation of their expression, which suggest that a precise level of global NOTCH expression and NOTCH-dependent transcriptional activity of specific targets could be necessary to determine the final phenotype of 3T3-L1 adipocytes.

Violencia basada en género dentro del contexto universitario: Visión de los administrativos, 2013-2015 / Gender-based violence within the university context: Vision of administrative 2013-2015

Introducción: Estudiar el tema de la violencia basada en género en el contexto universitario representa un reto, dado que se considera más en el ámbito privado y no se visibiliza en lo público, además es naturalizado por la cultura. Objetivo: Comprender el fenómeno de la violencia basada en género desde la visión de los administrativos en una Institución de Educación Superior. Materiales y métodos: Estudio basado en el paradigma cualitativo con enfoque de Investigación-Acción. Como técnicas se emplearon: entrevista a informantes clave, observación participante, grupo focal y taller. Resultados: El conocimiento sobre la Violencia Basada en Género es superficial, los tipos de violencia más reconocidos fueron la violencia sexual y la psicológica, se reconoce naturalización del fenómeno en la institución y; frecuentemente se aduce que la falta de reacción mostrada por quienes la viven u observan, ocurre como resultado del miedo a represalias. Conclusiones: La visibilización del problema ayudó a comprender las directrices de un fenómeno como la violencia basada en género, que debe orientarse en múltiples escenarios académicos e institucionales y con diversas estrategias que conjuntamente orientadas pueden generar un impacto significativo.

Introduction: To study the issue of gender-based violence (GBV) in the university context is a challenge, since it is considered more in the private sphere, it is not dealt openly in public and it is naturalized by culture. Objective: Understand the phenomenon of GBV from the perspective of the administration in an institution of higher education. Materials and methods: A study based on the qualitative paradigm with action research approach was conducted. The adopted techniques were; interviews with key informants, participant observation, focus group and interventional workshop. Results: The knowledge of administrative workers on GBV is superficial. However, the types of violence more recognized were sexual and psychological violence. The naturalization of the phenomenon in the institution was recognized and it was often argued that the lack of reaction shown by those who live or observe this type of violence occurs as a result of the fear of reprisals. Conclusions: The visibility of the problem helped to understand the guidelines of a phenomenon such as gender-based violence, which should be directed in many academic and institutional scenarios and with various strategies that jointly oriented can generate a significant impact.

Improving cardiovascular health in Spanish seafarers.

BACKGROUND AND AIM: There is a high prevalence in the Spanish general population of some cardiovascular risk factors like overweight, obesity and hypercholesterolaemia. But there is lack of research on Spanish seafarers. On the other hand, there is strong evidence of the cardiovascular risk predictive value of some biomarkers. The purpose of this work was to study the convenience of the introduction of detailed diet questionnaires and the measurement of some biomarkers in the pre-embarkation medical examination. MATERIALS AND METHODS: Seafarers undergoing medical checkup during 2011 in Madrid, Spain (n = 334). Overweight and obese subjects received general advice on healthy diet and physical activity. Seventy-four of them were followed up in 2012 and 2013. Glycated haemoglobin (HbA1c), high-sensitivity C-reactive protein (hs-CRP), thyrotropin (TSH) and microalbuminuria were measured in two selected groups of patients in 2011. RESULTS: Overweight and obesity were present in 207 (62%) individuals of the studied population. Those followed up in 2012 and 2013 showed a reduction of body mass index, waist circumference and total cholesterol values. We observed risk value of HbA1c in 60 (35.5%) individuals with significant association to other cardiovascular risk factors. Microalbuminuria appeared in subjects with high blood pressure. High TSH and hs-CRP were not significantly present in our population. CONCLUSIONS: 1. Measurement of HbA1c during medical checkups improves early detection of cardiovascular risk in seafarers. 2. Individuals with overweight and obesity responded positively to medical advice and diminished their risk factors, thus it may be more effective to introduce detailed questionnaires on this issue.

Lesiones por accidentes de trabajo relacionados con el tráfico ocurridas en los trabajadores de una entidad bancaria (2007-2013) / Occupational traffic injuries in workers from a spanish bank Company (2007-2013)

Objetivos: Describir las lesiones por accidentes de trabajo (LAT) relacionados con el tráfico (LATT) ocurridas en los trabajadores de una entidad bancaria desde 2007 a 2013 en España. Adicionalmente, describir las características de las LATT en función de sexo y edad de los accidentados, así como la ocurrencia de bajas médicas en relación con este tipo de lesiones. Métodos: Estudio transversal descriptivo del registro de LAT mantenido por el servicio de prevención de la empresa estudiada. Se describen las frecuencias absolutas (n) y relativas (%) en relación con las características de interés. Para las comparaciones se utiliza el test chi cuadrado. Resultados: En una plantilla total de 14.541 trabajadores, en el periodo de estudio se registraron 1.517 LAT. El 27% de estas LAT fueron LATT. El 1,3% de las LATT fueron considerados graves o mortales. Se observan relaciones significativas (p<0,05) con el sexo y la edad. Las lesiones en copilotos, las LATT 'in itinere' y el diagnóstico 'esguinces/torceduras' son más frecuentes en las mujeres. Las LATT 'en desplazamiento' y el diagnóstico'fracturas cerradas' son más frecuentes en los hombres. También es más frecuente la situación de baja médica en caso de LATT en comparación con las LAT. Conclusiones: La frecuencia de LATT sobre el total de LAT en la muestra estudiada es casi tres veces mayor que en la población laboral general española, aunque en nuestro estudio las LATT graves son menos frecuentes. Las LATT presentan diferencias en su distribución según edad y sexo de los trabajadores, y también se asocian con mayor frecuencia a baja médica en comparación con el conjunto de las LAT. La salud pública y la medicina del trabajo deben buscar estrategias para controlar este tipo de lesiones

Objective: To study physical harm caused by road accidents (LATT in Spanish) among employees of a Spanish financial institution from 2007 to 2013. Additionally, we tried to define damage features in each sex and at different ages in hurt patients, as well as work disability caused by this type of injury. Methods: Cross-sectional study of labor injuries verified by the occupational medical service of the bank. Absolute (n) and relative (%) frequencies related to interesting variables were described. Chi-square test was used to assess correlation. Results: Along the mentioned period of time, 1.517 traumatic occupational injuries were recorded on a population of 14.541 workers. 27% of them were LATT. 1,3% of these were fatal or seriously harmful, significantly associated to sex and age (p< 0,05). Co-driver damage, LATT in itinere and twist or sprain were more common in women. LATT at work and closed fractures were more frequent in men.Work disability caused by LATT was higher than other traumatic occupational injuries. Conclusions: LATT in the studied sample were almost three times higher than LATT are among general Spanish population, but serious lesions in our group were less common.We observed differences in LATT distribution by sexes and ages in workers included in this study, and also a higher incidence of work disability compared to the whole traumatic occupational injuries. Public health and occupational health authorities must find efficient strategies in order to diminish the incidence of these LATT-associated injuries