First order transitions by conduction calorimetry: Application to deuterated potassium dihydrogen phosphate ferroelastic crystal under uniaxial pressure

The specific heat c and the heat power W exchanged by a Deuterated Potassium Dihydrogen Phosphate ferroelectric-ferroelastic crystal have been measured simultaneously for both decreasing and increasing temperature at a low constant rate (0.06 K/h) between 175 and 240 K. The measurements were carried out under controlled uniaxial stresses of 0.3 and 4.5±0.1 bar applied to face (110). At Tt=207.9 K, a first order transition is produced with anomalous specific heat behavior in the interval where the transition heat appears. This anomalous behavior is explained in terms of the temperature variation of the heat power during the transition. During cooling, the transition occurs with coexistence of phases, while during heating it seems that metastable states are reached. Excluding data affected by the transition heat, the specific heat behavior agrees with the predictions of a 2-4-6 Landau potential in the range of 4–15 K below Tt while logarithmic behavior is obtained in the range from Tt to 1 K below Tt. Data obtained under 0.3 and 4.5 bar uniaxial stresses exhibit the same behavior.Dirección General de Investigación Científica y Técnica. Gobierno de España-PB91-60

Estudio de la distribución de hidrógeno en una contención PWR con códigos CFD

Durante el desarrollo de un accidente severo en un reactor PWR, se pueden generar grandes cantidades de hidrógeno por la oxidación de los metales presentes en el núcleo, principalmente el zirconio de las vainas del combustible. Este hidrógeno, junto con vapor y otros gases, puede ser liberado a la atmósfera de la contención por una fuga o rotura en el circuito primario y alcanzar condiciones en las que pueda darse combustión. La combustión provoca cargas térmicas y de presión que pueden dañar los sistemas de seguridad y la integridad del edificio de contención, última barrera de confinamiento de los materiales radiactivos. La principal condición que define las características de la combustión es la concentración de especies, por lo que el conocimiento detallado de la distribución de hidrógeno resulta muy importante para predecir correctamente los posibles daños en la contención en el caso de que se produjera combustión

Insights into the procoagulant profile of patients with systemic lupus erythematosus without antiphospholipid antibodies

We aimed to identify the key players in the prothrombotic profile of patients with systemic lupus erythematosus (SLE) not mediated by antiphospholipid antibodies, as well as the potential utility of global coagulation tests to characterize hemostasis in these patients. Patients with SLE without antiphospholipid antibodies and without signs of thrombosis were included. The kinetics of clot formation were determined by ROTEM®. Platelet activation markers were determined by flow cytometry. Thrombin generation associated with Neutrophil Extracellular Traps (NETs) and microparticles (MPs) was measured by calibrated automated thrombogram (CAT). The plasma levels of PAI-1 were also determined. ROTEM® showed a procoagulant profile in SLE patients. SLE patients had activated platelets and more leukocyte/platelet aggregates at basal conditions. The plasma PAI-1 and platelet aggregates correlated with several ROTEM® parameters. The thrombin generation associated withthe tissue factor (TF) content of MPs and with NETs was increased. Our results suggest the utility of global tests for studying hemostasis in SLE patients because they detect their procoagulant profile, despite having had neither antiphospholipid antibodies nor any previous thrombotic event. A global appraisal of hemostasis should, if possible, be incorporated into clinical practice to detect the risk of a thrombotic event in patients with SLE and to consequently act to prevent its occurrenceThis work was supported by grant from the FIS-FONDOS FEDER (PI19/00772, NVB). E.M.M. holds a predoctoral fellowship from Fundación Española de Trombosis y Hemostasia (FETH-SETH

IAA : Información y actualidad astronómica (31)

Sumario : Relámpagos en las alturas.-- El misterio de Di Herculis.-- Jets en galaxias activas.-- HISTORIAS DE ASTRONOMÍA. Los All-Star de la física.-- DECONSTRUCCIÓN Y otros ENSAYOS. Cómo “encender” un cuásar .-- EL “MOBY DICK” DE... María Rosa Zapatero Osorio (CAB, CSIC-INTA).-- ACTUALIDAD.-- ENTRE BASTIDORES.-- CIENCIA: PILARES E INCERTIDUMBRES : El Sistema Solar: ¿conocemos de verdad nuestro vecindario?.-- ACTIVIDADES IAA, AGENDA Y RECOMENDADOS.N

Splicing factor SF3B1 is overexpressed and implicated in the aggressiveness and survival of hepatocellular carcinoma

Splicing alterations represent an actionable cancer hallmark. Splicing factor 3B subunit 1 (SF3B1) is a crucial splicing factor that can be targeted pharmacologically (e.g. pladienolide-B). Here, we show that SF3B1 is overexpressed (RNA/protein) in hepatocellular carcinoma (HCC) in two retrospective (n = 154 and n = 172 samples) and in five in silico cohorts (n > 900 samples, including TCGA) and that its expression is associated with tumor aggressiveness, oncogenic splicing variants expression (KLF6-SV1, BCL-XL) and decreased overall survival. In vitro, SF3B1 silencing reduced cell viability, proliferation and migration and its pharmacological blockade with pladienolide-B inhibited proliferation, migration, and formation of tumorspheres and colonies in liver cancer cell lines (HepG2, Hep3B, SNU-387), whereas its effects on normal-like hepatocyte-derived THLE-2 proliferation were negligible. Pladienolide-B also reduced the in vivo growth and the expression of tumor-markers in Hep3B-induced xenograft tumors. Moreover, SF3B1 silencing and/or blockade markedly modulated the activation of key signaling pathways (PDK1, GSK3b, ERK, JNK, AMPK) and the expression of cancer-associated genes (CDK4, CD24) and oncogenic SVs (KLF6-SV1). Therefore, the genetic and/or pharmacological inhibition of SF3B1 may represent a promising novel therapeutic strategy worth to be explored through randomized controlled trials.Las alteraciones en el splicing son un rasgo distintivo del cáncer. La subunidad 1 del factor de splicing 3B (SF3B1) es un factor de splicing crucial que puede ser objeto de tratamiento farmacológico (por ejemplo, pladienolide-B). En este estudio demostramos que SF3B1 está sobreexpresado (ARN/proteína) en el carcinoma hepatocelular (CHC) en dos cohortes retrospectivas (n = 154 y n = 172 muestras) y en cinco cohortes in silico (n > 900 muestras, incluyendo TCGA) y que su expresión está asociada con la agresividad tumoral, la expresión de variantes de splicing oncogénicas (KLF6-SV1, BCL-XL) y la disminución de la supervivencia global. In vitro, el silenciamiento de SF3B1 redujo la viabilidad, proliferación y migración celular, y su bloqueo farmacológico con pladienolide-B inhibió la proliferación, migración y formación de esferas tumorales y colonias en líneas celulares de cáncer de hígado (HepG2, Hep3B, SNU-387), mientras que sus efectos sobre la proliferación de THLE-2 derivadas de hepatocitos de tipo normal fueron insignificantes. Pladienolide-B también redujo el crecimiento in vivo y la expresión de marcadores tumorales en tumores xenoinjertados inducidos por Hep3B. Además, el silenciamiento y/o bloqueo de SF3B1 moduló notablemente la activación de vías de señalización clave (PDK1, GSK3b, ERK, JNK, AMPK) y la expresión de genes asociados al cáncer (CDK4, CD24) y de SV oncogénicos (KLF6-SV1)

CD229 (Ly9) a Novel Biomarker for B-Cell Malignancies and Multiple Myeloma

CD229 is a cell-surface molecule predominantly expressed on lymphocytes. Its expression in B-cell malignancies is poorly known. We tested the presence of this immunoreceptor on a large number of malignancies and normal tissue using a new monoclonal antibody and tissue microarrays. Our data show that CD229 expression is restricted to hematopoietic cells. It was strongly expressed in myeloma and marginal-zone lymphomas. Because of the high expression on multiple myeloma cells, we also analyze the presence of soluble CD229 in the sera of these patients. We showed that serum levels of soluble CD229 in myeloma patients, at the time of diagnosis, could be useful as a prognostic biomarker. Altogether, our results indicate that CD229 represents not only a useful disease biomarker but also an attractive therapeutic target. CD229 (Ly9) homophilic receptor, which belongs to the SLAM family of cell-surface molecules, is predominantly expressed on B and T cells. It acts as a signaling molecule, regulating lymphocyte homoeostasis and activation. Studies of CD229 function indicate that this receptor functions as a regulator of the development of marginal-zone B cells and other innate-like T and B lymphocytes. The expression on leukemias and lymphomas remains poorly understood due to the lack of CD229 monoclonal antibodies (mAb) for immunohistochemistry application (IHC). In this study, we used a new mAb against the cytoplasmic region of CD229 to study the expression of CD229 on normal tissues and B-cell malignancies, including multiple myeloma (MM), using tissue microarrays. We showed CD229 to be restricted to hematopoietic cells. It was strongly expressed in all cases of MM and in most marginal-zone lymphomas (MZL). Moderate CD229 expression was also found in chronic lymphocyte leukemia (CLL), follicular (FL), classic mantle-cell (MCL) and diffuse large B-cell lymphoma. Given the high expression on myeloma cells, we also analyzed for the presence of soluble CD229 in the sera of these patients. Serum levels of soluble CD229 (sCD229) at the time of diagnosis in MM patients could be useful as a prognostic biomarker. In conclusion, our results indicate that CD229 represents not only a useful biomarker but also an attractive therapeutic target

Perspectiva de género en la asignatura de farmacología

En este proyecto de innovación docente hemos trabajo para comenzar a poner las bases de posibles diferencias que pueden existir en la farmacología de los medicamentos, atendiendo a si la persona que los toma es un hombre o una mujer. Con alumnos del grado de Nutrición Humana y Dietética y de Odontología hemos buscado bibliografía que nos demuestre si efectivamente se dan estas diferencias en la farmacocinética, en la farmacodinamia y en los efectos adversos. Los resultados encontrados nos han permitido presentar 2 comunicaciones en congresos y realizar un TFGDepto. de Farmacología y ToxicologíaFac. de MedicinaFALSEsubmitte

Incidence, typology and measures of prevention and treatment of skin lesions associated with the use of personal protective equipment in health care professionals during the COVID-19 pandemic in Spain

Introducción: La reciente pandemia de COVID-19 ha representado la utilización por parte de los profesionales de la salud de diferentes equipos de protección individual (EPI), lo que ha dado lugar a la aparición de lesiones cutáneas asociadas a los mismos (LC-EPI). Conocer la epidemiología, las características y los factores relacionados con el uso de los diferentes tipos de EPI y la prevención y el tratamiento de las LC-EPI puede ser muy útil para comprender el alcance del problema y definir estrategias para su prevención y tratamiento en posibles pandemias futuras. Métodos: Estudio transversal realizado por el Grupo Nacional para el Estudio y Asesoramiento en Úlceras por Presión y Heridas Crónicas (GNEAUPP) en el ámbito geográfico del Estado español, mediante una encuesta autoadministrada utilizando un cuestionario de Google Forms. El universo de estudio fueron profesionales de la salud, de cualquier disciplina y nivel asistencial o tipo de institución que habían estado en contacto con pacientes o sospechosos de COVID-19 y habían utilizado EPI durante la primera ola de la pandemia de COVID-19 en España. Resultados: Se obtuvieron 2078 cuestionarios, el 75,5% de enfermeras, el 10,79% de técnicos en cuidados auxiliares de enfermería (TCAE) y el 6,6% de médicos. De los respondedores, el 84,7% eran mujeres y el 15,3% hombres con una edad media de 43,7 años. En el 18,2% de los casos, la institución del profesional contaba con un protocolo para la prevención de las LC-EPI, en el 10,2% el profesional no sabía si existía y en el 71,3% restante la institución no contaba con dicho protocolo. El 29,9% de los profesionales utilizaba siempre algún producto de prevención de LC-EPI y el 25,3% en ocasiones. El 52,4% de los encuestados informó haber presentado al menos una LC-EPI, de los cuales el 39% había presentado una, el 35,8% dos, el 14,3% tres, el 2,2% cuatro y el 8,6% más de cuatro. En relación con el tipo de lesiones, el 74,3% fueron definidas como lesiones por presión (LPP), el 11% como lesiones por fricción (LF), el 8,5% como lesiones combinadas o multicausales (LCMC) y el 6,1% como lesiones cutáneas asociadas a la humedad (LESCAH). La duración media de las lesiones incidentes fue de 11,6 días (9,7 días para las LPP, 10,2 días para las LF, 19,9 días para las LCMC y 19,4 días para las LESCAH). En el artículo se presenta información más detallada por tipo de dispositivo causante, tipología y gravedad de las lesiones por dispositivo, así como las medidas preventivas utilizadas.Introduction: The recent COVID-19 pandemic has represented the use by health care professionals (HCP) of different personal protective equipment (PPE), resulting in the appearance of skin injuries associated with PPE (PPE-SI). Knowing the epidemiology, characteristics and factors related to the use of different types of PPE and the prevention and treatment of PPE-SI can be very useful to understand the scope of the problem and to define strategies for its prevention and treatment in possible future pandemics. Methods: To this end, the GNEAUPP proposed the performance of a cross-sectional study, in the geographical area of the Spanish state, by means of a self-administered survey using a Google forms questionnaire. The study universe was HCP, from any discipline and from any level of care or type of institution with patients who have been in contact with COVID-19 patients or COVID-19 suspects and have used PPE during the first wave of the COVID-19 pandemic in Spain. Main results: We obtained 2078 questionnaires, 75.5% from nurses, 10.79% from nurse aids, and 6.6% from physicians. Of these, 84.7% were women and 15.3% were men with an average age of 43.7 years. In 18.2% of the cases the institution of the professional had a protocol for the prevention of PPE-SI, in 10.2% the professional did not know if it existed or not and in the remaining 71.3% the institution did not have such a protocol. 29.9% of the professionals always used some prevention product and 25.3% sometimes. 52.4% of respondents reported having submitted at least one PPE-SI, of which 39% had submitted one, 35.8% two, 14.3% three, 2.2% four and 8.6% more than four. In relation to PPE-SI, 74.3% were defined as pressure injuries (PI), 11% were friction injuries (FI), 8.5% were combined or multicausal injuries (CMCI) and 6.1% were skin injuries associated with moisture (MASI). The mean duration of incident injuries was 11.6 days (9.7 days for PI, 10.2 days for FI, 19.9 days for CMCI and 19.4 days for MASI). More detailed Information is presented in the paper by type of device causing, typology and severity of injuries per device as well as preventive measures used

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio