Extracellular vesicles-based biomarkers represent a promising liquid biopsy in endometrial cancer

Tumor-derived extracellular vesicles (EVs) are secreted in large amounts into biological fluids of cancer patients. The analysis of EVs cargoes has been associated with patient´s outcome and response to therapy. However, current technologies for EVs isolation are tedious and low cost-e cient for routine clinical implementation. To explore the clinical value of circulating EVs analysis we attempted a proof-of-concept in endometrial cancer (EC) with ExoGAG, an easy to use and highly e cient new technology to enrich EVs. Technical performance was first evaluated using EVs secreted by Hec1A cells. Then, the clinical value of this strategy was questioned by analyzing the levels of two well-known tissue biomarkers in EC, L1 cell adhesion molecule (L1CAM) and Annexin A2 (ANXA2), in EVs purified from plasma in a cohort of 41 EC patients and 20 healthy controls. The results demonstrated the specific content of ANXA2 in the purified EVs fraction, with an accurate sensitivity and specificity for EC diagnosis. Importantly, high ANXA2 levels in circulating EVs were associated with high risk of recurrence and non-endometrioid histology suggesting a potential value as a prognostic biomarker in EC. These results also confirmed ExoGAG technology as a robust technique for the clinical implementation of circulating EVs analysesThis research was funded by Instituto de Salud Carlos III, grant PI17/01919, co-financed by the European Regional Development Fund (FEDER), and by Fundación Científica de la Asociación Española Contra el Cáncer (AECC), Grupos Clínicos Coordinados 2018. Carolina Herrero is supported by a predoctoral i-PFIS fellowship from Instituto de Salud Carlos III (IFI17/00047); Laura Muinelo is supported by Asociación Española Contra el Cáncer (AECC)

Internal structure of the nanogratings generated inside bulk fused silica by ultrafast laser direct writing

The aim of the present work was to characterize the internal structure of nanogratings generated inside bulk fused silica by ultrafast laser processing and to study the influence of diluted hydrofluoric acid etching on their structure. The nanogratings were inscribed at a depth of 100μm within fused silica wafers by a direct writing method, using 1030nm radiation wavelength and the following processing parameters: E=5μJ, τ=560 fs, f=10kHz, and v=100μm/s. The results achieved show that the laser-affected regions are elongated ellipsoids with a typical major diameter of about 30μm and a minor diameter of about 6μm. The nanogratings within these regions are composed of alternating nanoplanes of damaged and undamaged material, with an average periodicity of 351±21nm. The damaged nanoplanes contain nanopores randomly dispersed in a material containing a large density of defects. These nanopores present a roughly bimodal size distribution with average dimensions for each class of pores 65±20×16±8×69±16nm 3 and 367±239×16±8×360±194nm 3, respectively. The number and size of the nanopores increases drastically when an hydrofluoric acid treatment is performed, leading to the coalescence of these voids into large planar discontinuities parallel to the nanoplanes. The preferential etching of the damaged material by the hydrofluoric acid solution, which is responsible for the pores growth and coalescence, confirms its high defect density

Diagnóstico etiológico de la disfunción ventricular izquierda con tomografía computarizada: comparación con coronariografía y cardiorresonancia

[EN] Introduction and objectives To evaluate the capability of multidetector computed tomography to diagnose the coronary etiology of left ventricular dysfunction compared with using invasive coronary angiography and magnetic resonance. Methods Forty consecutive patients with left ventricular dysfunction of uncertain etiology underwent invasive coronary angiography and contrast magnetic resonance. All patients were evaluated with multidetector computed tomography including coronary calcium presence and score, noninvasive coronary angiography, and myocardial tissue assessment. Results The sensitivity and specificity of the presence of coronary calcium to identify left ventricular dysfunction was 100% and 31%, respectively. If an Agatston calcium score of >100 is taken, specificity increases to 58% with sensitivity still 100%. Sensitivity and specificity for coronary angiography by multidetector computed tomography was 100% and 96%, respectively; for identifying necrosis in contrast acquisition it was 57% and 100%, respectively; and in late acquisition, 84% and 96%, respectively. To identify coronary ventricular dysfunction with necrosis, the sensitivity and specificity was 92% and 100%, respectively. Conclusions Of all the diagnostic tools available in multidetector computed tomography, coronary angiography is the most accurate in determining the coronary origin of left ventricular dysfunction. A combination of coronary angiography and myocardial tissue study after contrast allows a single test to obtain similar information compared with the combination of invasive coronary angiography and contrast magnetic resonance.[ES] Introducción y objetivos Evaluar la capacidad de la tomografía computarizada con multidetectores en el diagnóstico de la disfunción ventricular izquierda de origen coronario y valorar su exactitud diagnóstica comparándola con la combinación de coronariografía invasiva y resonancia magnética. Métodos Se estudió a 40 pacientes consecutivos con disfunción ventricular izquierda de origen no filiado mediante coronariografía invasiva y resonancia con contraste. A todos ellos se les realizó además un estudio de tomografía computarizada con multidetectores incluyendo presencia de calcio coronario y su cuantificación, coronariografía y valoración tisular del miocardio. Resultados La sensibilidad y la especificidad de la presencia de calcio coronario para identificar la disfunción ventricular izquierda de origen coronario fueron del 100 y el 31% respectivamente. Si se considera un score de calcio por Agatston >100, la especificidad sube al 58% manteniendo la sensibilidad del 100%. Los valores de sensibilidad y especificidad de la coronariografía por tomografía computarizada con multidetectores fueron del 100 y el 96% respectivamente; para la identificación de áreas de necrosis en la adquisición precoz, del 57 y el 100% y en la adquisición tardía, del 84 y el 96%. Para identificar a los pacientes coronarios con necrosis, la sensibilidad y la especificidad fueron del 92 y el 100% respectivamente. Conclusiones De todas las herramientas diagnósticas disponibles en tomografía computarizada con multidetectores, la coronariografía es la que muestra mayor exactitud diagnóstica para determinar el origen coronario de la disfunción ventricular. La combinación del estudio coronariográfico y el estudio tisular del miocardio tras el contraste permite obtener en un solo examen información similar a la de la combinación de cateterismo y resonancia con contraste.This work was supported in part by a grant from the Fundacion Espanola del Corazon and Fuente Liviana 2009 of Sociedad Espanola de Cardiologia. F. Ridocci received assistance from the Instituto de Salud Carlos III Research Activity Intensification Programme 2010.Estornell-Erill, J.; Igual-Muñoz, B.; Monmeneu-Menadas, JV.; Soriano-Navarro, C.; Valle-Muñoz, A.; Vilar Herrero, JV.; Perez-Bosca, L.... (2012). Etiological diagnosis of left ventricular dysfunction: computed tomography compared with coronary angiography and cardiac magnetic resonance. Revista Española de Cardiología. 65(6):517-524. https://doi.org/10.1016/j.rec.2011.07.011S51752465

Etiological Diagnosis of Left Ventricular Dysfunction: Computed Tomography Compared With Coronary Angiography and Cardiac Magnetic Resonance

[EN] Introduction and objectives: To evaluate the capability of multidetector computed tomography to diagnose the coronary etiology of left ventricular dysfunction compared with using invasive coronary angiography and magnetic resonance. Methods: Forty consecutive patients with left ventricular dysfunction of uncertain etiology underwent invasive coronary angiography and contrast magnetic resonance. All patients were evaluated with multidetector computed tomography including coronary calcium presence and score, noninvasive coronary angiography, and myocardial tissue assessment. Results: The sensitivity and specificity of the presence of coronary calcium to identify left ventricular dysfunction was 100% and 31%, respectively. If an Agatston calcium score of >100 is taken, specificity increases to 58% with sensitivity still 100%. Sensitivity and specificity for coronary angiography by multidetector computed tomography was 100% and 96%, respectively; for identifying necrosis in contrast acquisition it was 57% and 100%, respectively; and in late acquisition, 84% and 96%, respectively. To identify coronary ventricular dysfunction with necrosis, the sensitivity and specificity was 92% and 100%, respectively. Conclusions: Of all the diagnostic tools available in multidetector computed tomography, coronary angiography is the most accurate in determining the coronary origin of left ventricular dysfunction. A combination of coronary angiography and myocardial tissue study after contrast allows a single test to obtain similar information compared with the combination of invasive coronary angiography and contrast magnetic resonance. © 2012 Sociedad Española de Cardiología. Published by Elsevier España, S.L. All rights reserved.[ES] Introducción y objetivos Evaluar la capacidad de la tomografía computarizada con multidetectores en el diagnóstico de la disfunción ventricular izquierda de origen coronario y valorar su exactitud diagnóstica comparándola con la combinación de coronariografía invasiva y resonancia magnética. Métodos Se estudió a 40 pacientes consecutivos con disfunción ventricular izquierda de origen no filiado mediante coronariografía invasiva y resonancia con contraste. A todos ellos se les realizó además un estudio de tomografía computarizada con multidetectores incluyendo presencia de calcio coronario y su cuantificación, coronariografía y valoración tisular del miocardio. Resultados La sensibilidad y la especificidad de la presencia de calcio coronario para identificar la disfunción ventricular izquierda de origen coronario fueron del 100 y el 31% respectivamente. Si se considera un score de calcio por Agatston > 100, la especificidad sube al 58% manteniendo la sensibilidad del 100%. Los valores de sensibilidad y especificidad de la coronariografía por tomografía computarizada con multidetectores fueron del 100 y el 96% respectivamente; para la identificación de áreas de necrosis en la adquisición precoz, del 57 y el 100% y en la adquisición tardía, del 84 y el 96%. Para identificar a los pacientes coronarios con necrosis, la sensibilidad y la especificidad fueron del 92 y el 100% respectivamente. Conclusiones De todas las herramientas diagnósticas disponibles en tomografía computarizada con multidetectores, la coronariografía es la que muestra mayor exactitud diagnóstica para determinar el origen coronario de la disfunción ventricular. La combinación del estudio coronariográfico y el estudio tisular del miocardio tras el contraste permite obtener en un solo examen información similar a la de la combinación de cateterismo y resonancia con contraste.Estornell-Erill, J.; Igual-Muñoz, B.; Monmeneu-Menadas, JV.; Soriano-Navarro, C.; Valle-Muñoz, A.; Vilar Herrero, JV.; Perez-Bosca, L.... (2012). Diagnóstico etilógico de la disfunción ventricular izquierda con tomografia computerizada: comparación con coronariografía y cardiorresonancia. Revista Española de Cardiología. 65(6):517-524. doi:10.1016/j.recesp.2011.07.012S51752465

Atomic Force Microscopy under Controlled Conditions Reveals Structure of C-Terminal Region of alpha-Synuclein in Amyloid Fibrils.

Item does not contain fulltextAtomic force microscopy (AFM) is widely used to measure morphological and mechanical properties of biological materials at the nanoscale. AFM is able to visualize and measure these properties in different environmental conditions. However, these conditions can influence the results considerably, rendering their interpretation a matter of some subtlety. We demonstrate this by imaging approximately 10 nm diameter alpha-synuclein amyloid fibrils, focusing specifically on the structure of the C-terminal part of the protein monomers incorporated into fibrils. Despite these influences leading to variations in fibril heights, we have shown that by maintaining careful control of AFM settings we can quantitatively compare the morphological parameters of fibrils imaged in air or in buffer conditions. From this comparison we were able to deduce the semiflexible character of this C-terminal region. Fibril height differences measured in air and liquid indicate that the C-terminal region collapses onto the fibril core upon drying. The fibril heights decrease upon increasing ion concentration in solution, suggesting that the C-terminal tails collapse into more compact structures as a result of charge screening. Finally, PeakForce QNM measurements show an apparent heterogeneity of C-terminal packing along the fibril length