Involvement of extracellular vesicles in the macrophage-tumor cell communication in head and neck squamous cell carcinoma

Exosomes; Larynx cancer cells; MacrophagesExosomes; Cèl·lules cancerígenes de la laringe; MacròfagsExosomas; Células cancerosas de laringe; MacrófagosBackground: Exosomes are cell-derived vesicles that mediate cellular communication in health and multiple diseases, including cancer. However, its role in head and neck cancer has been poorly defined. Here, we investigated the relevance of exosomes in the signaling between larynx cancer cells and macrophages. Methods: Exosomes from THP1 macrophages and BICR18 cells (a larynx squamous cell carcinoma cell line) were purified and their role in the cancer cell migration, macrophage phenotype and immunosuppressive activity was evaluated. The activation of STAT3 signal transduction in macrophages in response to exosomes obtained from cancer cells was also evaluated. Results: Macrophages foster the cancer cell migration and this effect is mediated by exosome signaling. On the other hand, exosomes also induce the expression of IL-10 in macrophages and PD-L1 in cancer cells, thus resulting in the promotion of an immunosuppressive environment. Moreover, we observed that the effects induced in cancer cells are mediated by the exosome-depending activation of STAT-3 signal transduction pathway. Conclusions: Our study indicates that exosomes released by both macrophages and cancer cells plays a critical role in tumor progression in larynx cancer and might be a potential target for therapeutic intervention in head and neck cancer.This work was supported by a research grant from the Carlos III Institute of Health with reference FIS PI16/00060 (D.C.), co-funded with European Union ERDF funds (European Regional Development Fund)

Reconstrucciones paleoclimáticas de la Península Ibérica desde una perspectiva de modelización

Ponencia presentada en: VII Congreso de la Asociación Española de Climatología: clima, ciudad y ecosistemas, celebrado en Madrid entre el 24 y 26 de noviembre de 2010.[ES]Se ha realizado una simulación de la evolución del clima en la Península Ibérica en el último milenio con el Modelo de Circulación Regional MM5 implementado con una resolución espacial de 30 km. Las condiciones de contorno para el modelo regional se han tomado del Modelo de Circulación General ECHO-G, que implementa una resolución espacial de 300 km aproximadamente sobre la Península Ibérica. Los forzamientos externos de ambos modelos están basados en reconstrucciones de la evolución de la potencia solar, concentraciones de gases de efecto invernadero y efectos radiativos debidos a grandes erupciones volcánicas. El modelo regional mejora la reproducción del clima en la península y es capaz de detectar diferencias regionales que el modelo global no capta. Por lo tanto, esta nueva simulación contribuye a entender mejor los mecanismos físicos responsables de eventos climáticos del pasado, y así mejorar nuestra comprensión de la evolución del clima en el futuro.[EN]A simulation of the climate of the Iberian Peninsula (IP) for the last millennium has been performed with the Regional Circulation Model MM5, implemented with a spatial resolution of 30 km. The experiment is driven by the General Circulation Model ECHO-G, which implements a spatial resolution about 300 km over the IP. External forcings are based on reconstructions of the evolution of the solar constant power, Green House Gases and the radiative effects of big volcano events. The regional model improves the simulation of the local climate, and depicts important differences respect to the global model. This simulation contributes to the understanding the physical mechanism under important past climate events, and hence improves our comprehension of the evolution of the future climate

Análisis de extremos de temperatura en un conjunto de proyecciones de cambio climático para la Península Ibérica

Ponencia presentada en: VII Congreso de la Asociación Española de Climatología: clima, ciudad y ecosistemas, celebrado en Madrid entre el 24 y 26 de noviembre de 2010.[ES]Uno de los aspectos más interesantes del cambio climático es su efecto sobre fenómenos extremos. Para conseguir proyecciones de futuro fiables de fenómenos extremos es conveniente contar con simulaciones de alta resolución espacial en las que se tengan en cuenta efectos locales. Los modelos regionales de simulación climática son una herramienta muy utilizada para este propósito. Sin embargo, las fuentes de incertidumbre que afectan a este tipo de simulaciones van desde el escenario de emisiones futuro que se considere hasta la propia configuración física del modelo regional. En este trabajo se evalúan las incertidumbres asociadas a la configuración física de un modelo regional a partir de un conjunto de proyecciones de futuro de extremos de temperatura para la Península Ibérica. Concretamente se analizan los cambios proyectados para las funciones de distribución de probabilidad de la temperatura máxima diaria de verano. Los resultados muestran que el aumento de la temperatura media ira acompañado por una mayor variabilidad y asimetría de las funciones de distribución, y que la incertidumbre que introduce elegir unas u otras parametrizaciones físicas es del orden del 50% de los cambios medios que se proyectan. Sin embargo, la evaluación de la bondad de las simulaciones del presente permite discriminar cuales son a priori las proyecciones más fiables.[EN]The effect of climate change over extreme events is one of the most interesting aspect for researches. In order to gain confidence in future projections of extreme events, high resolution simulations in which local effects are taken into account are required. Regional climate models are a very used tool to get them. Nevertheless, these simulations are affected by several sources of uncertainty, from the future emission scenario to the physics configuration of the regional model. In this work, the uncertainties due to the physics configuration of a regional model are evaluated through an ensemble of future projections of temperature extremes over the Iberian Peninsula. In concrete, the projected changes of the probability density functions of summer season daily maximum temperature are analyzed. Results show that the increase of the mean temperature will be accompained by a greater variability and a greater assimetry of the distribution functions, and also that the uncertainty due to the election of the physic parameterizations is about 50% of the mean projected changes. Nevertheless, evaluating the performance of the present simulations allows to discriminate the most reliable projections

Climatología del viento sobre la Península Ibérica: observaciones y modelos

Ponencia presentada en: IX Congreso de la Asociación Española de Climatología celebrado en Almería entre el 28 y el 30 de octubre de 2014.[ES]En este trabajo se presenta la climatología del viento en la Península Ibérica (PI) obtenida a partir de datos de más de 500 estaciones con registros horarios para el periodo 1999-2007. Se describen distintos aspectos; rosa de los vientos, funciones de distribución de probabilidad, ciclo anual y respuesta a distintos tipos de circulación del campo de vientos a escala regional (20 regiones). Las regiones fueron obtenidas a partir de un análisis clúster imponiendo máxima similitud temporal entre las series observacionales.[EN]In this work the wind climatology of the Iberian Peninsula is presented. It has been obtained using more tan 500 weather stations with hourly records for the period 1999-2007. Wind Roses, annual cycles and probability distribution functions as well as the response of the wind field to circulation types are characterized at regional scale. Regions are obtained using a a cluster analysis, grouping places with similar temporal variability.Este trabajo ha sido financiado por el Gobierno de España y el Fondo Europeo de Desarrollo Regional (FEDER) por medio de los proyectos MINIEOLICA (PSE.120000.2007.14), CORWES (CGL210-22158) y SPEQ-TRES (CGL2011-29672-C02-02)

Proyecciones a medio plazo de cambios climáticos en los recursos solar y eólico sobre la Península Ibérica

Ponencia presentada en: IX Congreso de la Asociación Española de Climatología celebrado en Almería entre el 28 y el 30 de octubre de 2014.[ES]Las energías renovables son parte fundamental de las estrategias de mitigación del cambio climático, pero también un sector potencialmente afectado por este último. La Península Ibérica (PI) presenta también esta doble faceta: un gran potencial para el desarrollo, en particular, de parques solares y eólicos y una alta vulnerabilidad al cambio climático. En este contexto, el objetivo de este trabajo es investigar los cambios proyectados a medio plazo, y las incertidumbres asociadas, en los campos de viento y de radiación solar superficiales.[EN]Renewable energies are an important part of the mitigation strategies aimed at abating climate change, but simultaneously they are one of the sectors threatened by this latter. The Iberian Peninsula (IP) shows also a similar twofold: a great potential for the development of solar plants and wind farms, in particular, and a high vulnerability to climate change effects. In such a context, the objective of this work is to investigate medium-term projected changes, and associated uncertainties, in the surface wind and solar radiation fields

Análisis del papel de la elección en la base de datos reticular observacional en la evaluación de modelos climáticos regionales

Ponencia presentada en: VIII Congreso de la Asociación Española de Climatología celebrado en Salamanca entre el 25 y el 28 de septiembre de 2012.[ES]En este trabajo se presentan los resultados de la evaluación de la habilidad de todos los miembros de dos conjuntos de simulaciones regionales climáticas para la reproducción de la precipitación y temperaturas máximas y mínimas utilizando tres bases de datos reticulares diferentes (SPAIN02, AEMET y E-OBS), que tienen una resolución espacial similar (aprox 25 km). El primer conjunto es multifísica (30 km) y consta de ocho miembros. El segundo conjunto es multimodelo (ESCENA) y consta de 5 miembros (25 km de resolución). Los resultados indican que la bondad de los miembros del conjunto en la reproducción de la climatología observada sobre España depende de las base de datos seleccionada.[EN]This paper presents the results of the skill evaluation of the members of two ensembles of regional climate simulations in reproducing precipitation and maximum and minimum temperatures using three different grid databases (SPAIN02, AEMET and E-OBS ), which have similar spatial resolution (approximately 25 km). The first set is multiphysics (30 km) and consists of eight members. The second set is multi-model (ESCENA) and consists of 5 members (25 km resolution). The results indicate that the skill of the ensemble members in reproducing the observed climate over Spain depends on the selected database

SDCBP Modulates Stemness and Chemoresistance in Head and Neck Squamous Cell Carcinoma through Src Activation

Cèl·lules mare del càncer; QuimioresistènciaCélulas madre del cáncer; QuimiorresistenciaCancer stem cells; ChemoresistanceTo characterize the mechanisms that govern chemoresistance, we performed a comparative proteomic study analyzing head and neck squamous cell carcinoma (HNSCC) cells: CCL-138 (parental), CCL-138-R (cisplatin-resistant), and cancer stem cells (CSCs). Syntenin-1 (SDCBP) was upregulated in CCL-138-R cells and CSCs over parental cells. SDCBP depletion sensitized biopsy-derived and established HNSCC cell lines to cisplatin (CDDP) and reduced CSC markers, Src activation being the main SDCBP downstream target. In mice, SDCBP-depleted cells formed tumors with decreased mitosis, Ki-67 positivity, and metastasis over controls. Moreover, the fusocellular pattern of CCL-138-R cell-derived tumors reverted to a more epithelial morphology upon SDCBP silencing. Importantly, SDCBP expression was associated with Src activation, poor differentiated tumor grade, advanced tumor stage, and shorter survival rates in a series of 382 HNSCC patients. Our results reveal that SDCBP might be a promising therapeutic target for effectively eliminating CSCs and CDDP resistance.This research was supported by grants from the Instituto de Salud Carlos III (ISCIII): PI15/01262 and CP03/00101 (M.E.LL.), PI19/00560 (J.G.-P.), and CIBERONC (M.E.LL. and IDI2018/155 J.P.R.) and was co-financed by the European Regional Fund (ERDF) and AECC (Spanish Association of Cancer Research) Founding Ref. GC16173720CARR (M.E.LL.). Y.G.M. and C.M. were supported by the VHIR and iP-FIS (ISCIII) fellowships, respectively. We acknowledge the Principado de Asturias BioBank (PT17/0015/0023)

Evaluation of C-reactive protein, Haptoglobin and cardiac Troponin 1 levels in brachycephalic dogs with upper airway obstructive syndrome

Background: Brachycephalic dogs have unique upper respiratory anatomy with abnormal breathing patterns similar to those in humans with obstructive sleep apnea syndrome (OSAS). The objective of this study was to evaluate the correlation between anatomical components, clinical signs and several biomarkers, used to determine systemic inflammation and myocardial damage (C-reactive protein, CRP; Haptoglobin, Hp; cardiac troponin I, cTnI), in dogs with brachycephalic upper airway obstructive syndrome (BAOS). Results: Fifty brachycephalic dogs were included in the study and the following information was studied: signalment, clinical signs, thoracic radiographs, blood work, ECG, components of BAOS, and CRP, Hp and cTnI levels. A high proportion of dogs with BAOS (88%) had gastrointestinal signs. The prevalence of anatomic components of BAOS was: elongated soft palate (100%), stenotic nares (96%), everted laryngeal saccules (32%) and tracheal hypoplasia (29.1%). Increased serum levels of biomarkers were found in a variable proportion of dogs: 14% (7/50) had values of CRP > 20 mg/L, 22.9% (11/48) had values of Hp > 3 g/L and 47.8% (22/46) had levels of cTnI > 0.05 ng/dl. Dogs with everted laryngeal saccules had more severe respiratory signs (p<0.02) and higher values of CRP (p<0.044). No other statistical association between biomarkers levels and severity of clinical signs was found. Conclusions: According to the low percentage of patients with elevated levels of CRP and Hp, BAOS does not seem to cause an evident systemic inflammatory status. Some degree of myocardial damage may occur in dogs with BAOS that can be detected by cTnI concentration

A finite element-based machine learning approach for modeling the mechanical behavior of the breast tissues under compression in real-time

[EN] This work presents a data-driven method to simulate, in real-time, the biomechanical behavior of the breast tissues in some image-guided interventions such as biopsies or radiotherapy dose delivery as well as to speed up multimodal registration algorithms. Ten real breasts were used for this work. Their deformation due to the displacement of two compression plates was simulated off-line using the finite element (FE) method. Three machine learning models were trained with the data from those simulations. Then, they were used to predict in real-time the deformation of the breast tissues during the compression. The models were a decision tree and two tree-based ensemble methods (extremely randomized trees and random forest). Two different experimental setups were designed to validate and study the performance of these models under different conditions. The mean 3D Euclidean distance between nodes predicted by the models and those extracted from the FE simulations was calculated to assess the performance of the models in the validation set. The experiments proved that extremely randomized trees performed better than the other two models. The mean error committed by the three models in the prediction of the nodal displacements was under 2 man, a threshold usually set for clinical applications. The time needed for breast compression prediction is sufficiently short to allow its use in real-time (< 0.2 s).This work has been funded by the Spanish Ministry of Economy and Competitiveness (MINECO) through research projects TIN2014-52033-R and DPI2013-40859-R with the support of European FEDER funds.Martínez Martínez, F.; Rupérez Moreno, MJ.; Martínez-Sober, M.; Solves Llorens, JA.; Lorente, D.; Serrano-Lopez, A.; Martinez-Sanchis, S.... (2017). A finite element-based machine learning approach for modeling the mechanical behavior of the breast tissues under compression in real-time. Computers in Biology and Medicine. 90:116-124. https://doi.org/10.1016/j.compbiomed.2017.09.019S1161249

Procediment d’extracció de taps de cerumen

Extracció de tap de cerumen; Rentat d'orella; Infermeria en atenció primàriaExtracción de tapón de cerumen; Lavado de oreja; Enfermería en atención primariaCerumen plug removal; Ear wash; Nursing primary careAquest document presenta com cal permeabilitzar el conducte auditiu garantint la realització correcta de la tècnica de rentat d'orella i s'adreça a tot professional sanitari que hagi de procedir a l'extracció d'un tap de cerumen