68 research outputs found

    Proteomic characterization of human coronary thrombus in patients with ST-segment elevation acute myocardial infarction

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    Acute myocardial infarction with ST-segment elevation (STEMI) initiates with intraluminal thrombosis and results in total occlusion of the coronary artery. To date, characterization of the coronary thrombus proteome in STEMI patients has not been yet accomplished. Therefore, we aimed to perform an in-depth proteomic characterization of the human coronary thrombus by means of three different approaches: 2-DE followed by mass spectrometry (MALDI MS/MS), 1-DE combined either with liquid chromatography coupled to mass spectrometry in a MALDI TOF/TOF (LC-MALDI-MS/MS), or in a LTQ-Orbitrap (LC-ESI-MS/MS). This approach allowed us to identify a total of 708 proteins in the thrombus. Expression in coronary thrombi (n=20) of 14 proteins was verified, and the expression of fibrin and 6 cell markers (platelets, monocytes, neutrophils, eosinophils, T-cells and B-cells) quantified by selected reaction monitoring (SRM). A positive correlation of 5 proteins (fermitin homolog 3, thrombospondin-1, myosin-9, beta parvin and ras-related protein Rap-1b) with CD41 was found, pointing out the potential activation of a focal adhesion pathway within thrombus platelets. DIDO1 protein was found to correlate negatively with thrombus fibrin, and was found up-regulated in the plasma of these STEMI patients, which may constitute a starting point for further analyses in the search for biomarkers of thrombosis. BIOLOGICAL SIGNIFICANCE: The proteomic characterization of the human coronary thrombus may contribute to a better understanding of the mechanisms involved in acute coronary syndrome, and thus pave the road for the identification of new therapeutic targets that may help addressing this and other thrombotic diseases. A novel methodology to characterize thrombus composition and expression of a sub-group of proteins is hereby described, which allowed linking protein expression with cellular and ECM matrix composition of the thrombus. Five proteins (fermitin homolog 3, thrombospondin-1, myosin-9, beta parvin and ras-related protein Rap-1b) co-express within the human coronary thrombus with CD41, pointing out the potential activation of a focal adhesion pathway within thrombus platelets during thrombus formation. Besides, the protein death-inducer obliterator 1, found to be expressed within the human coronary thrombus, has been proved to increase in the plasma of STEMI patients, which constitutes an important starting point for further analyses in the search for biomarkers of thrombosis.This work was supported by grants from the Instituto de Salud Carlos III (FIS PI070537, PI11/02239), Fondos Feder, Redes temáticas de Investigación Cooperativa en Salud (RD12/0042/ 0071, RD06/0014/1015), and Fundación para la Investigación Sanitaria de Castilla-La Mancha (FISCAM PI2008-08, PI2008-28, PI2008-52). These results are lined up with the Spanish initiative on the Human Proteome Project (SpHPP). The CNIC is supported by the Spanish Ministerio de Economia y Competitividad and the Fundacion Pro-CNIC. We would like to thank Dr. Gloria Alvarez-Llamas for her kind suggestions for the manuscript; Gemma Barroso from Proteomic Unit, Hospital Nacional de Paraplejicos, for her help and dedication to this work, as well as Veronica Moral and Ana Gallardo from the same Unit, and TamaraSastre andCarmenBermudez for their technical support.S

    Roadmap on measurement technologies for next generation structural health monitoring systems

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    Structural health monitoring (SHM) is the automation of the condition assessment process of an engineered system. When applied to geometrically large components or structures, such as those found in civil and aerospace infrastructure and systems, a critical challenge is in designing the sensing solution that could yield actionable information. This is a difficult task to conduct cost-effectively, because of the large surfaces under consideration and the localized nature of typical defects and damages. There have been significant research efforts in empowering conventional measurement technologies for applications to SHM in order to improve performance of the condition assessment process. Yet, the field implementation of these SHM solutions is still in its infancy, attributable to various economic and technical challenges. The objective of this Roadmap publication is to discuss modern measurement technologies that were developed for SHM purposes, along with their associated challenges and opportunities, and to provide a path to research and development efforts that could yield impactful field applications. The Roadmap is organized into four sections: distributed embedded sensing systems, distributed surface sensing systems, multifunctional materials, and remote sensing. Recognizing that many measurement technologies may overlap between sections, we define distributed sensing solutions as those that involve or imply the utilization of numbers of sensors geometrically organized within (embedded) or over (surface) the monitored component or system. Multi-functional materials are sensing solutions that combine multiple capabilities, for example those also serving structural functions. Remote sensing are solutions that are contactless, for example cell phones, drones, and satellites. It also includes the notion of remotely controlled robots

    Outcomes of nonagenarians after transcatheter aortic valve implantation

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    Introduction and objectives: Nonagenarians are a fast-growing age group among cardiovascular patients, especially with aortic stenosis, but data about their prognosis after transcatheter aortic valve implantation (TAVI) is scarce. The objective of our study is to analyze the baseline characteristics of nonagenarians treated with TAVI and determine whether age = 90 years is associated with a worse prognosis compared to non-nonagenarian patients. Methods: We included all patients =75 years enrolled in the multicenter prospective Spanish TAVI registry between 2009 and 2018. Patients < 75 years were excluded. Results: A total of 8073 elderly patients (= 75 years) from 46 Spanish centers were enrolled in the Spanish TAVI registry; 7686 were between = 75 and < 90 years old (95.2%), and 387 were nonagenarian patients (4.79%). A gradual increase of nonagenarians was observed. The transfemoral access was used in 91.6% of the cases, predominantly among the nonagenarian patients (91.4% vs 95.1%, P = .01). Nonagenarians were more likely to die during their hospital stay (4.3% vs 7.0% among nonagenarians, P = .01). However, no difference was seen in the all-cause mortality rates reported at the 1-year follow-up (8.8% vs 11.3%, P =.07). In the multivariate analysis, age = 90 years was not independently associated with a higher adjusted all-cause mortality rate (HR, 1.37, 95%CI, 0.91–1.97, P = .14). The baseline creatinine levels, and the in-hospital bleeding complications were all associated with a worse long-term prognosis in nonagenarians treated with TAVI. Conclusions: Nonagenarians are a very high-risk and growing population with severe AS in whom TAVI may be a safe and effective strategy. Careful patient selection by the TAVI heart team is mandatory to achieve maximum efficiency in this population where the baseline kidney function and bleeding complications may determine the long-term prognosis after TAVI. © 2021 Sociedad Española de Cardiología. Published by Permanyer Publications
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