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)

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

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

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Is there a common pattern of future gas-phase air pollution in Europe under diverse climate change scenarios?

Climate change alone influences future levels of tropospheric ozone and their precursors through modifications of gas-phase chemistry, transport, removal, and natural emissions. The goal of this study is to determine at what extent the modes of variability of gas-phase pollutants respond to different climate change scenarios over Europe. The methodology includes the use of the regional modeling system MM5 (regional climate model version)-CHIMERE for a target domain covering Europe. Two full-transient simulations covering from 1991–2050 under the SRES A2 and B2 scenarios driven by ECHO-G global circulation model have been compared. The results indicate that the spatial patterns of variability for tropospheric ozone are similar for both scenarios, but the magnitude of the change signal significantly differs for A2 and B2. The 1991–2050 simulations share common characteristics for their chemical behavior. As observed from the NO2 and α-pinene modes of variability, our simulations suggest that the enhanced ozone chemical activity is driven by a number of parameters, such as the warming-induced increase in biogenic emissions and, to a lesser extent, by the variation in nitrogen dioxide levels. For gas-phase pollutants, the general increasing trend for ozone found under A2 and B2 forcing is due to a multiplicity of climate factors, such as increased temperature, decreased wet removal associated with an overall decrease of precipitation in southern Europe, increased photolysis of primary and secondary pollutants as a consequence of lower cloudiness and increased biogenic emissions fueled by higher temperatures