134 research outputs found

    CORELLATION OF LATE TRIASSIC AND EARLY JURASSIC LOFER-TYPE CARBONATES FROM THE PELOPONNESUS PENINSULA, GREECE

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    Correlation of the Late Triassic carbonate successions, formed at the passive Pelagonian margin (SE of Dhidymi Mt.) with the Early-Middle Liassic successions of the Gavrovo-Tripolitza zone (SE of Leonidion), in eastern and central Peloponnesus respectively, is attempted. Detailed microfacies analysis revealed that the studied carbonate formations were deposited in analogous restricted inner-platform environments (lagoon-peritidal domain) and are composed of meter-scale, shallowing-upward, mostly incomplete peritidal cycles. The top of the supratidal and/ or shallow subtidal deposits are often affected by meteoric diagenesis tracing sea-level lowering and periodic emersions episodes. The well-developed pedogenic features observed in the Early Jurassic platform carbonates indicate long-lasting subaerial exposure intervals and semi-arid to arid climate. Instead, the Late Triassic strata preserve vadose diagenetic indices which point to shorter exposure events, weaker meteoric alteration and slightly wetter climatic conditions. The detected sedimentological features suggest the occurrence of wide lagoonal-peritidal depositional systems during Late Triassic and Early Jurassic, eastern and western of the Pindos basin, respectively. The basic facies pattern and the meter-scale cyclicity show many analogies with the Lofer cycles of the Alpine Triassic, supporting that in the Hellenides the Dachstein-type platform systems evolved till Early-Middle Liassic (Gavrovo-Tripolitza zone)

    Requirements and validation of a prototype learning health system for clinical diagnosis

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    Introduction Diagnostic error is a major threat to patient safety in the context of family practice. The patient safety implications are severe for both patient and clinician. Traditional approaches to diagnostic decision support have lacked broad acceptance for a number of well-documented reasons: poor integration with electronic health records and clinician workflow, static evidence that lacks transparency and trust, and use of proprietary technical standards hindering wider interoperability. The learning health system (LHS) provides a suitable infrastructure for development of a new breed of learning decision support tools. These tools exploit the potential for appropriate use of the growing volumes of aggregated sources of electronic health records. Methods We describe the experiences of the TRANSFoRm project developing a diagnostic decision support infrastructure consistent with the wider goals of the LHS. We describe an architecture that is model driven, service oriented, constructed using open standards, and supports evidence derived from electronic sources of patient data. We describe the architecture and implementation of 2 critical aspects for a successful LHS: the model representation and translation of clinical evidence into effective practice and the generation of curated clinical evidence that can be used to populate those models, thus closing the LHS loop. Results/Conclusions Six core design requirements for implementing a diagnostic LHS are identified and successfully implemented as part of this research work. A number of significant technical and policy challenges are identified for the LHS community to consider, and these are discussed in the context of evaluating this work: medico-legal responsibility for generated diagnostic evidence, developing trust in the LHS (particularly important from the perspective of decision support), and constraints imposed by clinical terminologies on evidence generation

    Vacancy-Driven Noncubic Local Structure and Magnetic Anisotropy Tailoring in FeₓO-Fe₃-{δ}_O₄ Nanocrystals

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    In contrast to bulk materials, nanoscale crystal growth is critically influenced by size- and shape-dependent properties. However, it is challenging to decipher how stoichiometry, in the realm of mixed-valence elements, can act to control physical properties, especially when complex bonding is implicated by short- and long-range ordering of structural defects. Here, solution-grown iron-oxide nanocrystals (NCs) of the pilot wüstite system are found to convert into iron-deficient rock-salt and ferro-spinel subdomains but attain a surprising tetragonally distorted local structure. Cationic vacancies within chemically uniform NCs are portrayed as the parameter to tweak the underlying properties. These lattice imperfections are shown to produce local exchange-anisotropy fields that reinforce the nanoparticles’ magnetization and overcome the influence of finite-size effects. The concept of atomic-scale defect control in subcritical-size NCs aspires to become a pathway to tailor-made properties with improved performance for hyperthermia heating over defect-free NCs

    Preliminary results of high resolution paleoceanography and paleoclimatology during sapropel S1 deposition (South Limnos Basin, North Aegean Sea).

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    Οι παλαιοπεριβαλλοντικές συνθήκες κατά τη διάρκεια απόθεσης του σαπροπηλού S1 στο Βόρειο Αιγαίο (πυρήνας βαρύτητας Μ-4, μήκους 2,53 m, λεκάνης νότιας Λήμνου) προσδιορίζονται με βάση την ποσοτική ανάλυση μικροπαλαιοντολογικών (βενθονικά και πλαγκτονικά τρηματοφόρα) και γεωχημικών (OC, δ13Corg) δεικτών. Χαρακτηριστικό του πυρήνα Μ-4 είναι η μεγάλη εμφάνιση του S1 που φτάνει το πάχος των 96 cm. Η μελέτη κατέδειξε ότι, το κατώτερο σαπροπηλικό στρώμα S1a αποτέθηκε σε θερμότερες συνθήκες, εντονότερης δυσοξίας, σε σχέση με το ανώτερο σαπροπηλικό στρώμα S1b.. Αύξηση της παραγωγικότητας και καλύτερη διατήρηση του οργανικού υλικού πιστοποιήθηκαν στο κατώτερο τμήμα του S1. Η διακοπή των σαπροπηλικών συνθηκών στα 8,0 Ka BP που χαρακτηρίζεται κυρίως από την αύξηση της σχετικής συχνότητας των συμφυρματοπαγών μορφών των βενθονικών τρηματοφόρων υποστηρίζει συνθήκες υψηλής οξυγόνωσης του πυθμένα και εισροή γλυκών υδάτων.The paleoenviromental conditions during the depositional interval of sapropel S1 in the northeastern Aegean (gravity core M-4, length 2.53 m; south Limnos basin) are studied based on quantitative micropaleontological (benthic and planktonic foraminifera) and geochemical (OC, δ13Corg) analyses. Special feature of core M-4 is the thickness of S1 layer (96 cm). Our study points that sapropelic layer S1a has been deposited in more dysoxic and warmer conditions in respect to S1b. Both primary productivity and preservation of organic material are more intense during the lower part of S1. An interruption of the sapropelic conditions at 8.0 Ka BP which is mainly characterized by the increase of agglutinated foraminiferal forms confirms both higher oxygen bottom conditions and freshwater input

    Determination of the effect of collars containing 10% w/w imidacloprid and 4.5% w/w flumethrin (SerestoÂŽ) on the incidence of Leishmania and other canine vector-borne pathogen infections in Greece

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    Background: The objective of this field study was to assess the effect of treating a considerable portion of a dog population naturally exposed to canine vector-borne pathogens (CVBPs) in endemic areas with a 10% w/w imidacloprid/4.5% w/w flumethrin collar (SerestoŽ) on the transmission of CVBPs and the resulting incidence of infection. Methods: A total of 479 dogs from two sites were enrolled in the study. Collars were placed on all dogs continuously for 21 months, with replacement of the collar every 7 months. All dogs were examined, including body weight and blood/conjunctival swab collections, every 7 months. Serum samples were analysed for the presence of antibodies against Leishmania infantum, Ehrlichia canis and Anaplasma phagocytophilum. PCR assays were also performed on blood samples and conjunctival swab collected from the dogs for the presence of L. infantum, and on blood samples only for the presence of Ehrlichia spp. and Anaplasma spp. Sand flies were collected, identified to species level and molecularly tested for L. infantum throughout two vector activity seasons. Results: The results showed that the Seresto collar was safe with continuous use. At study inclusion, 419, 370 and 453 dogs tested negative for L. infantum, Ehrlichia spp. and Anaplasma spp., respectively (353 dogs tested negative for any pathogen). Overall, 90.2% of the dogs were protected from L. infantum infection on both sites combined. The entomological survey confirmed the presence of competent vectors of L. infantum at all monitored locations, namely the sand flies Phlebotomus neglectus and Phlebotomus tobbi, both of which are regarded as the most important competent vectors in the Mediterranean basin. All captured sand flies tested negative for L. infantum. Protection against ticks and fleas was high, with only two dogs showing a low number of ticks and seven dogs having low numbers of fleas at single evaluation time points. Across the entire study population, a number of dogs became infected with tick-transmitted pathogens, but prevention of transmission was 93% for E. canis and 87.2% for Anaplasma spp. when all cases from both sites were combined. Conclusions: The SerestoŽ (10% w/w imidacloprid/4.5% w/w flumethrin) collar significantly reduced the risk of CVBP transmission when compared to previously observed incidences of CVBP infections in two highly endemic areas under field conditions

    Report of the Regional Coordination Meeting for the North Atlantic (RCM NA) 2015

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    The 12th RCM North Atlantic was held in Hamburg (Germany) 14-18 September 2015. The main purpose of the RCM is to coordinate the National Programmes (NP) of the Member States (MS) in the North Atlantic region. National Programmes for 2011-2013 have been rolled over for the period 2014-2016. Therefore, the main focus at this year was to improve regional data collection, analysis and storage and the evolution towards Regional Coordination Groups (RCG).The impact of the introduction of the landing obligation and preparations for its implementation was also discussed taking into account possible changes in scientific sampling schemes. The participation of four National Correspondents make possible to address National administration issues related to the oncoming EU MAP. A data call was launched by the chairs of the RCM NA, RCM Baltic and RCM NS&EA where MS were requested to upload data for 2014 in the regional database (RDB Fishframe) hosted by ICES. All MS except France and Northern Ireland complied with this request on landings and effort data. All MS except France uploaded sample data for 2014. French data were available for the meeting using a web base interface. Evaluation of the data call for submission data to the RDB revealed the numbers of species in landings and sample data and the numbers of metiers in effort data are in general data stable. RCM NA see big improvements in the work MS are doing regarding data calls coming from a situation where some countries didn´t provide any data to a new scenario where everyone is providing data; at the same time the overall quality has significantly improved, which is a large step forward. Regional data collection, analysis, storage and the evolution towards Regional Coordination Groups (RCG). Optimizing and harmonizing fisheries management across MS is dependent on improving regional coordination. The group discussed various needs and aspects relevant for facilitating future work of the RCM. Future tasks for the RCM don’t differ much from the current tasks. The discussion was focused on the structure of the RCGs, funding and short term needs to address tasks in an efficient way in the future. Regional coordination encompasses many different aspects, ranging from regional cooperation, sampling design, quality control procedures, data storage and analysis to the actual coordination, reporting and accountancy. Current task sharing and coordination procedures as well as future mechanisms are partially covered under the current MARE study 2014/19 (FISHPI). The project and its progress were presented to the group. The outcomes of this study will demonstrate future procedures based on case studies. As substantial effort and costs are involved to facilitate the process of regional coordination, the group highlighted the importance to access to budgets to cover these costs. Development of the RDB is also crucial for future work of the RCGs; funds are needed for the development. Additionally, RCM NA identified 4 supra regional topics where work can be done intersesionally in cooperation with the rest of RCMs: (1) Cost sharing of funding surveys; (2) Impact of landing obligation; (3) reviewing the ICES list of data needs ; and (4) review and follow up on RDB upload logs. Due to the importance to moving to a regional catch sampling scheme, an exercise was realised using the distribution of landings by harbour and fleet segment as a proxy of sampling frames that could hypothetically operate in a regional probability based design. The exercise was based on landing weight, for the simple reason that this was the only complete variable that was available for all the various national data sets. A regional sampling design can however be optimized in any number of ways (e.g. by landings value, by métier diversity, by species diversity, by number of fishing trips). The aims and aspirations of the end users need to be defined to ascertain which is most appropriate. It is one of the overriding advantages of a regional sampling design (as opposed to the aggregation of national designs) that the overall coverage can be set out to achieve regional goals. The RCM NA analyzed and discussed the main achievements of WKISCON2. It was clear that concurrent sampling at-sea is a long-established practice in most MS and that, where it was applied, concurrent sampling of fishing trips on-shore resulted in substantial increases in species collected without jeopardizing the main uses of data. Stock assessment and discard estimation and management are the major current uses of concurrent sampling data. Concurrent sampling has also been providing other benefits than its initial reason, such as advice to local, national and international authorities, research on MSFD descriptors, mixed fisheries and gear interactions and on mortality of rare species, data-poor stocks and PETS. It was clear that concurrent sampling being a statistically valid method for species selection which has proven to fulfil different end-users needs, implementation constraints hinder concurrent sampling on-shore. Thus, in order to meet end-users needs and to overcome the constraints that may arise from the implementation of concurrent sampling in some countries, particularly on-shore, RCM NA considers that different statistically sound approaches other than concurrent sampling must be developed to be tested in the field, so they may provide useful alternatives. Introduction of the landing obligation and its impact in the implementation in scientific sampling schemes. In terms of evaluating the impact of the introduction of the Landing Obligation (LO) regulation on data collection, there is only limited experience as the current implementation only covers Pelagic and Industrial fisheries in this region but MS have or are preparing for the implementation where they can. It is currently perceived that this year is a transition period for the pelagic fisheries and that these fisheries and control agencies are not fully implementing the LO (managing but not enforcing). As a result MS did not have a lot of comments on the current year and are in general preparing for next year. During the meeting it was decided to gather further information to address this issue by getting member states who were present to fill in a table on “Monitoring the impact of the landing obligation on data collection in the North Atlantic region” outlining the current state of play. This table could be considered as a live document which should be filled in year by year as the Landing Obligation is phased in. This table will then serve to provide an historical record as countries can document the changes year by year and will also provide guidance and act as a learning tool to all member states on how other countries are implementing the LO. National administrations The group discussed the proposal for task sharing and criteria for joint surveys. RCM NS&EA and RCM NA 2014 discussed a cost model for the present joint MS financed surveys and for future joint surveys. In addition to this model, the RCM NA 2015 highlighted that four categories of surveys should be considered in relation to task sharing and criteria for joint surveys. In the light of cost sharing, the group commented that the current DCF recast proposal refers to ‘exploitation of stocks’ rather than EU TAC or landings. Given the relative stability, EU TAC shares are the preferred basis for sharing costs. The exploitation of stocks shall be interpreted as EU-TAC share as a default. In specific cases, RCGs can in the future agree on different interpretation where needed and feasible. Fully agreement among the group was concerning to the engagement and participation of National Correspondent (NC) in this meeting. The future role of the NCs in the RCG context was discussed, indicating a formal role for the NCs in the RCG process to approve and agree on regional arrangements. However, the current recast of the DCF doesn’t include the formal involvement of the NCs in the coordination procedures and meetings. RCM NA highlights this as potentially problematic for the foreseen formal role of the NCs. Other items on the agenda were the consideration of the follow up of relevant recommendations made last years by Liaison Meeting and presentations and relevant development from ICES, EC and SC-RDB

    Report of the 12th Liaison Meeting

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    The 12th Liaison meeting was held in Brussels on 8th and 9th October 2015 to address the following Terms of Reference: TOR 1. Discussion on possible follow-­‐‑up to the main outputs/recommendations of: • The 2015 RCMs -­‐‑ specific recommendations addressed to the Liaison Meeting • PGECON, PGDATA, PGMed – outcomes and recommendations from their 2015 meeting • STECF EWG and STECF Plenary -­‐‑ outcomes and recommendations from their 2015 meetings • Data end users (ICES, STECF, RFMOs – GFCM, IATTC, ICCAT, IOTC, WCPFC, NAFO, SPRFMO, CECAF, WECAFC) TOR2. End user feedback on data transmission and related issues • Discuss feedback received from data end-­‐‑users on data transmission: main issues and possible harmonization of end user feedback to the Commission • JRC data transmission IT platform: experience gained and future steps • Discuss best practices on automatization of data upload by MS: data validation tools used by end users • Discussion on new set-­‐‑up for STECF evaluation of AR2014 & data transmission 2014 used in 2015 – continue like this next year? • Harmonisation and dissemination of DCF metadata: codelists, metiers, nomenclatures, best practices, standards • RCM data calls – overview of how MS responded TOR 3. Regional cooperation • Call for proposals MARE/2014/19 'ʹStrengthening Regional Cooperation in the area of fisheries data collection– state of play'ʹ. Presentation by a representative of the two RCG grants and discussions by LM thereafter. What should be the way forward? • Regional databases • Overview of use of the Regional Databases for RCMs in 2015 and problems identified • Other developments (RDB trainings in 2015, RDB Med&BS development) • Changes for the future – any recommendations from the LM? • Future role of RCMs and DCF-­‐‑related meetings: best practices, coordination, cohesion and common structure in line with emerging needs of DCF TOR 4. EU MAP • Discuss recommendations/ output of RCMs: List of proposed stocks, landing obligation, metiers • Discuss design-­‐‑based sampling in relation to DCF: does it fulfil DCF requirements? TOR 5. Availability of data • Overview of latest developments (DCF Database Feasibility Study and plans for a follow-­‐‑up study to this) TOR 6. AOB • Agree on a list of recommendations relating to DCF (that MS will need to report on in their AR2015) – COM will provide a compilation of proposed recommendations from LM & STECF Plenaries in 2014 as input • Prepare a list of recommended meetings for 2016 as guidance for MS • Review and prioritize DCF-­‐‑related study proposals from RCMs, PGECON, EGs etc • ICES update on workshop on concurrent sampling and plans to re-­‐‑evaluate survey

    OP0163 2019 UPDATE OF THE JOINT EUROPEAN LEAGUE AGAINST RHEUMATISM AND EUROPEAN RENAL ASSOCIATION–EUROPEAN DIALYSIS AND TRANSPLANT ASSOCIATION (EULAR/ERA-EDTA) RECOMMENDATIONS FOR THE MANAGEMENT OF LUPUS NEPHRITIS

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    Background:Up to 40% of systemic lupus erythematosus (SLE) patients develop kidney disease, which represents a major cause of morbidity.Objectives:To update the 2012 EULAR/ERA-EDTA recommendations for the management of lupus nephritis (LN).Methods:We followed the EULAR standardised operating procedures for the publication of treatment recommendations. Delphi-based methodology led to 15 questions for systematic literature review (SLR), which was undertaken by three fellows.Results:The changes include recommendations for treatment targets, use of glucocorticoids and calcineurin inhibitors (CNI), and management of end-stage-kidney-disease (ESKD). The target of therapy is complete response (proteinuria 1g/24h despite renin-angiotensin-aldosterone blockade, MMF in combination with glucocorticoids is preferred. Assessment for kidney and extra-renal disease activity, and management of comorbidities is lifelong with repeat kidney biopsy in cases of incomplete response or nephritic flares. In ESKD, transplantation is the preferred kidney replacement option with immunosuppression guided by transplant protocols and/or extra-renal manifestations.Conclusion:The updated recommendations intend to inform rheumatologists, nephrologists, patients, national professional societies, hospital officials, social security agencies and regulators about the treatment of LN based on most recent evidence.Disclosure of Interests:Antonis Fanouriakis Paid instructor for: Paid instructor for Enorasis, Amgen, Speakers bureau: Paid speaker for Roche, Genesis Pharma, Mylan, Myrto Kostopoulou: None declared, Kim Cheema: None declared, Hans-Joachim Anders: None declared, Martin Aringer Consultant of: Boehringer Ingelheim, Roche, Speakers bureau: Boehringer Ingelheim, Roche, Ingeborg Bajema Consultant of: GSK, John N. Boletis Grant/research support from: GSK, Pfizer, Paid instructor for: GSK, Abbvie, UCB, Enorasis, Eleni Frangou: None declared, Frederic Houssiau Grant/research support from: UCB, Consultant of: GSK, Jane Hollis: None declared, Alexandre Karras: None declared, Francesca Marchiori: None declared, Stephen Marks: None declared, Gabriela Moroni: None declared, Marta Mosca: None declared, Ioannis Parodis: None declared, Manuel Praga: None declared, Matthias Schneider Grant/research support from: GSK, UCB, Abbvie, Consultant of: Abbvie, Alexion, Astra Zeneca, BMS, Boehringer Ingelheim, Gilead, Lilly, Sanofi, UCB, Speakers bureau: Abbvie, Astra Zeneca, BMS, Chugai, GSK, Lilly, Pfizer, Sanofi, Josef S. Smolen Grant/research support from: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Consultant of: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Vladimir Tesar: None declared, Maria Trachana: None declared, Ronald van Vollenhoven Grant/research support from: AbbVie, Amgen, Arthrogen, Bristol-Myers Squibb, GlaxoSmithKline (GSK), Janssen Research & Development, LLC, Lilly, Pfizer, Roche, and UCB, Consultant of: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, Crescendo Bioscience, GSK, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, UCB and Vertex, Speakers bureau: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, Crescendo Bioscience, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, Vertex, Alexandre Voskuyl: None declared, Y.K. Onno Teng Grant/research support from: GSK, Consultant of: GSK, Aurinia Pharmaceuticals, Novartis, Bernadette van Leeuw: None declared, George Bertsias Grant/research support from: GSK, Consultant of: Novartis, David Jayne Grant/research support from: ChemoCentryx, GSK, Roche/Genentech, Sanofi-Genzyme, Consultant of: Astra-Zeneca, ChemoCentryx, GSK, InflaRx, Takeda, Insmed, Chugai, Boehringer-Ingelheim, Dimitrios Boumpas: None declare

    2019 update of the EULAR recommendations for the management of systemic lupus erythematosus

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    Š Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ. Our objective was to update the EULAR recommendations for the management of systemic lupus erythematosus (SLE), based on emerging new evidence. We performed a systematic literature review (01/2007-12/2017), followed by modified Delphi method, to form questions, elicit expert opinions and reach consensus. Treatment in SLE aims at remission or low disease activity and prevention of flares. Hydroxychloroquine is recommended in all patients with lupus, at a dose not exceeding 5 mg/kg real body weight. During chronic maintenance treatment, glucocorticoids (GC) should be minimised to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn. Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of GC. In persistently active or flaring extrarenal disease, add-on belimumab should be considered; rituximab (RTX) may be considered in organ-threatening, refractory disease. Updated specific recommendations are also provided for cutaneous, neuropsychiatric, haematological and renal disease. Patients with SLE should be assessed for their antiphospholipid antibody status, infectious and cardiovascular diseases risk profile and preventative strategies be tailored accordingly. The updated recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion

    Central Role of SREBP-2 in the Pathogenesis of Osteoarthritis

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    Background: Recent studies have implied that osteoarthritis (OA) is a metabolic disease linked to deregulation of genes involved in lipid metabolism and cholesterol efflux. Sterol Regulatory Element Binding Proteins (SREBPs) are transcription factors regulating lipid metabolism with so far no association with OA. Our aim was to test the hypothesis that SREBP-2, a gene that plays a key role in cholesterol homeostasis, is crucially involved in OA pathogenesis and to identify possible mechanisms of action. Methodology/Principal Findings: We performed a genetic association analysis using a cohort of 1,410 Greek OA patients and healthy controls and found significant association between single nucleotide polymorphism (SNP) 1784G>C in SREBP-2 gene and OA development. Moreover, the above SNP was functionally active, as normal chondrocytes’ transfection with SREBP-2-G/C plasmid resulted in interleukin-1β and metalloproteinase-13 (MMP-13) upregulation. We also evaluated SREBP-2, its target gene 3-hydroxy-3-methylglutaryl-coenzymeA reductase (HMGCR), phospho-phosphoinositide3-kinase (PI3K), phospho-Akt, integrin-alphaV (ITGAV) and transforming growth factor-β\beta (TGF-β\beta) mRNA and protein expression levels in osteoarthritic and normal chondrocytes and found that they were all significantly elevated in OA chondrocytes. To test whether TGF-β\beta alone can induce SREBP-2, we treated normal chondrocytes with TGF-β\beta and found significant upregulation of SREBP-2, HMGCR, phospho-PI3K and MMP-13. We also showed that TGF-β\beta activated aggrecan (ACAN) in chondrocytes only through Smad3, which interacts with SREBP-2. Finally, we examined the effect of an integrin inhibitor, cyclo-RGDFV peptide, on osteoarthritic chondrocytes, and found that it resulted in significant upregulation of ACAN and downregulation of SREBP-2, HMGCR, phospho-PI3K and MMP-13 expression levels. Conclusions/Significance: We demonstrated, for the first time, the association of SREBP-2 with OA pathogenesis and provided evidence on the molecular mechanism involved. We suggest that TGF-β\beta induces SREBP-2 pathway activation through ITGAV and PI3K playing a key role in OA and that integrin blockage may be a potential molecular target for OA treatment
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