3,725 research outputs found

    Non-Coding RNAs in Cell-to-Cell Communication: Exploiting Physiological Mechanisms as Therapeutic Targets in Cardiovascular Pathologies

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    Cardiovascular disease, the leading cause of death worldwide, has been characterized at the molecular level by alterations in gene expression that contribute to the etiology of the disease. Such alterations have been shown to play a critical role in the development of atherosclerosis, cardiac remodeling, and age-related heart failure. Although much is now known about the cellular and molecular mechanisms in this context, the role of epigenetics in the onset of cardiovascular disease remains unclear. Epigenetics, a complex network of mechanisms that regulate gene expression independently of changes to the DNA sequence, has been highly implicated in the loss of homeostasis and the aberrant activation of a myriad of cellular pathways. More specifically, non-coding RNAs have been gaining much attention as epigenetic regulators of various pathologies. In this review, we will provide an overview of the ncRNAs involved in cell-to-cell communication in cardiovascular disease, namely atherosclerosis, cardiac remodeling, and cardiac ageing, and the potential use of epigenetic drugs as novel therapeutic targets

    Systems Engineering Solution

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    The development and realisation of urban infrastructural projects such as bridges is getting increasingly more difficult and complex to manage. The challenge for the actors to develop an effective solution for the project within the traditional dimensions of time, budget and quality is still very present. But society also calls for more sustainable solutions which minimizes an eventual negative impact on the environment and takes into account the interests of stakeholders. The introduction of national and EU regulated procurement methods such as the Most Economically Advantageous Tenders (MEAT), has opened the way towards a more active and balanced involvement of actors and stakeholders in the development and realisation of urban construction projects. In this new environment, the client, consultant, contractor and stakeholders strive to work together in order to realise a sustainable solution. This document describes a methodology for the management of project processes with the aim of achieving a lawful, effective and sustainable construction process. The methodology is based on the principle of Life Cycle Systems Engineering, and facilitates and structures the introduction of sustainability and stakeholders issues in the design and build process. The method uses manly existing guidelines and standards for Life Cycle Systems Engineering

    Case report of a medication error by look-alike packaging: a classic surrogate marker of an unsafe system

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    Background: The acronym LASA (look-alike sound-alike) denotes the problem of confusing similar- looking and/or sounding drugs accidentally. The most common causes of medication error jeopardizing patient safety are LASA as well as high workload. Case presentation: A critical incident report of medication errors of opioids for postoperative analgesia by lookalike packaging highlights the LASA aspects in everyday scenarios. A change to a generic brand of medication saved costs of up to 16% per annum. Consequently, confusion of medication incidents occurred due to the similar appearance of the newly introduced generic opioid. Due to consecutive underdosing no life-threatening situation arose out of this LASA based medication error. Conclusion: Current recommendations for the prevention of LASA are quite extensive; still, in a system with a lump sum payment per case not all of these security measures may be feasible. This issue remains to be approached on an individual basis, taking into consideration local set ups as well as financial issues

    Growth factors for clinical-scale expansion of human articular chondrocytes : Relevance for automated bioreactor systems

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    The expansion of chondrocytes in automated bioreactors for clinical use requires that a relevant number of cells be generated, starting from variable initial seeding densities in one passage and using autologous serum. We investigated whether the growth factor combination transforming growth factor beta 1/fibroblast growth factor 2/platelet-derived growth factor BB (TFP), recently shown to enhance the proliferation capacity of human articular chondrocytes (HACs), allows the efficiency of chondrocyte use to be increased at different seeding densities and percentages of human serum (HS). HACs were seeded at 1,000, 5,000, and 10,000 celIS/cm(2) in medium containing 10 bovine serum or 10,000 cells/cm(2) with 1 chondrogenic capacity of post-expanded HACs was then assessed in pellet cultures. Expansion with TFP allowed a sufficient number of HACs to be obtained in one passage even at the lowest seeding density and HS percentage and variability in cartilage-forming capacity of HACs expanded under the different conditions to be reduced. Instead, larger variations and insufficient yields were found in the absence of TFP. By allowing large numbers of cells to be obtained, starting from a wide range of initial seeding densities and HS percentages, the use of TFP may represent a viable solution for the efficient expansion of HACs and addresses constraints of automated clinical bioreactor systems

    Role of macrophages in experimental group B streptococcal arthritis.

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    Septic arthritis is a clinical manifestation of group B Streptococcus (GBS) infection in both neonates and adults. Because macrophages are known to participate in tissue injury, the role of this cell population in GBS-induced arthritis was investigated. Mice were rendered monocytopenic by administration of etoposide, a drug that selectively depletes the monocyte/macrophage population and then injected with GBS (1 x 10(7) colony-forming units per mouse). Appearance of arthritis, mortality, GBS growth in the organs, and local and systemic cytokine production were examined. Etoposide-treated mice had a significantly less severe arthritis than control animals. Histopathological analysis of the joints confirmed clinical observations. Decreased joint levels of the proinflammatory cytokines interleukin 1 (IL-1) beta and IL-6 accompanied the less severe development of arthritis in monocytopenic mice. In contrast, mortality was increased in the etoposide-treated mice compared with controls. Monocytopenic mice exhibited elevated bacterial load in the blood and kidneys at all time points examined. These results indicate that lack of macrophages leads to less severe joint lesions, but also results in impaired clearance of bacteria, and consequent enhancement of mortality rates

    The Comparative Exploration of the Ice Giant Planets with Twin Spacecraft: Unveiling the History of our Solar System

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    In the course of the selection of the scientific themes for the second and third L-class missions of the Cosmic Vision 2015-2025 program of the European Space Agency, the exploration of the ice giant planets Uranus and Neptune was defined "a timely milestone, fully appropriate for an L class mission". Among the proposed scientific themes, we presented the scientific case of exploring both planets and their satellites in the framework of a single L-class mission and proposed a mission scenario that could allow to achieve this result. In this work we present an updated and more complete discussion of the scientific rationale and of the mission concept for a comparative exploration of the ice giant planets Uranus and Neptune and of their satellite systems with twin spacecraft. The first goal of comparatively studying these two similar yet extremely different systems is to shed new light on the ancient past of the Solar System and on the processes that shaped its formation and evolution. This, in turn, would reveal whether the Solar System and the very diverse extrasolar systems discovered so far all share a common origin or if different environments and mechanisms were responsible for their formation. A space mission to the ice giants would also open up the possibility to use Uranus and Neptune as templates in the study of one of the most abundant type of extrasolar planets in the galaxy. Finally, such a mission would allow a detailed study of the interplanetary and gravitational environments at a range of distances from the Sun poorly covered by direct exploration, improving the constraints on the fundamental theories of gravitation and on the behaviour of the solar wind and the interplanetary magnetic field.Comment: 29 pages, 4 figures; accepted for publication on the special issue "The outer Solar System X" of the journal Planetary and Space Science. This article presents an updated and expanded discussion of the white paper "The ODINUS Mission Concept" (arXiv:1402.2472) submitted in response to the ESA call for ideas for the scientific themes of the future L2 and L3 space mission
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