Publications
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Amindari A, Saltik L, Kirkkopru K, et al., 2017, Assessment of calcified aortic valve leaflet deformations and blood flow dynamics using fluid-structure interaction modeling, Informatics in Medicine Unlocked, Vol: 9, Pages: 191-199, ISSN: 2352-9148
Aortic valve diseases are among the most common cardiovascular defects. Since a non-functioning valve results in disturbed blood flow conditions, the diagnosis of such defects is based on identification of stenosis via echocardiography. Calculation of disease parameters such as valve orifice area or transvalvular pressure gradient using echocardiography is associated with substantial errors. Computational fluid dynamics (CFD) modeling has emerged as an alternative approach for accurate assessment of aortic valve hemodynamics. Fluid-structure interaction (FSI) modeling is adapted in these models to account for counter-interacting forces of flowing blood and deforming leaflets for most accurate results. However, implementation of this approach is difficult using custom built codes and algorithms. In this paper, we present an FSI modeling methodology for aortic valve hemodynamics using a commercial modeling software, ANSYS. We simulated the problem using fluid flow solver FLUENT and structural solver MECHANICAL APDL under ANSYS and coupled the solutions using System Coupling Module to enable FSI. This approach minimized adaptation problems that would raise if separate solvers were used. As an example case, we investigated influence of leaflet calcification on hemodynamic stresses and flow patterns. Model geometries were generated using b-mode echocardiography images of an aortic valve. A Doppler velocity measurement was used as velocity inlet boundary condition in the models. Simulation results were validated by comparing leaflet movements in the simulations with b-mode echo recordings. Wall shear stress levels, pressure levels and flow patterns agree well with previous studies demonstrating the accuracy of our results. Our modeling methodology can be easily adopted by researchers that are familiar with ANSYS and other similar CFD software to investigate similar biomedical problems.
El-Sherbiny IM, Sedki M, Soliman H, et al., 2017, Hydrogels for Pulmonary Drug Delivery, FUNCTIONAL HYDROGELS IN DRUG DELIVERY: KEY FEATURES AND FUTURE PERSPECTIVES, Editors: Spizzirri, Cirillo, Publisher: CRC PRESS-TAYLOR & FRANCIS GROUP, Pages: 327-351, ISBN: 978-1-4987-4901-5
Bednarczuk-Kaniewska E, Mielcarek M, Chester AH, et al., 2016, Oxidized low-density lipoproteins enhance expression and activity of CD39 and CD73 in the human aortic valve endothelium., Nucleosides, Nucleotides and Nucleic Acids, Vol: 35, Pages: 713-719, ISSN: 1525-7770
Extracellular nucleotides regulate thrombosis, inflammation and immune response.Ectonucleoside triphosphate diphosphohydrolase 1 (CD39) and ecto-5'-nucleotidase (CD73)convert extracellular nucleotides in a sequential order: ATP to ADP, AMP and then toadenosine. In this study, we aimed to test an effect of oxidized LDL (ox-LDL) on CD39 andCD73 in endothelial cells.Human aortic valve endothelial cells were exposed to oxidized low-densitylipoprotein, for 24-48 h. Next, the activity, protein expression and mRNA transcripts level ofCD39 and CD73 were characterised by: an incubation with ATP or AMP followed by HPLCanalysis of media as well as western blots and qPCR. Results are presented as mean ± SEM.CD73 activity in human valve endothelial cells was increased in presence of ox-LDL(4.04±0.32 nmol/mg prot./min) as compared to control (2.75±0.21 nmol/mg prot/min). Therewas almost no effect of ox-LDL on CD39 activity. A similar effect was observed for mRNAand protein expression.In conclusion, we found that ox-LDL modulated CD39 and CD73 activity in theendothelium, which may contribute to relevant pathologies and featured treatments.
Romeih S, Aguib H, Yacoub M, 2016, Utility of 4D Flow mapping in Eisenmenger syndrome with pulmonary atresia., Cardiol Young, Vol: 26, Pages: 1581-1589
Management of patients with Eisenmenger syndrome with pulmonary atresia is challenging because of the complexity of the structure-function relationship of the components of the syndrome. Multi-modality imaging including cardiac magnetic resonance (CMR) 4D Flow offers unprecedented opportunities to unravel, at least in part, some of these components, and thus help in the management of these patients. In this study, we describe the use of these integrated methods with particular reference to CMR 4D Flow in a patient with Eisenmenger syndrome and pulmonary atresia and outline both the utility and the limitations. A comprehensive cardiac magnetic resonance (CMR) 4D Flow analysis was performed preoperatively and postoperatively, during peak systole, late systole, early diastole, and late diastole. The focus of the present study was to investigate the pattern of flow and dynamic changes at different levels of the aorta, as well as in the duct and the pulmonary arteries. Preoperatively, a right-handed helix and a vortex were observed in the dilated ascending aorta, and the duct flow was mainly dependent on reverse, upstream flow from the descending aorta, distal to the duct, during diastole, denoting low pulmonary vascular capacitance. Following repair, the flow in the ascending aorta and the descending aorta changed markedly. These changes included both timing and intensity of the right-handed helix, as well as the vortex in the ascending aorta. The significance of the observed changes in flow pattern and their influence on wall structure and function are discussed. Our study demonstrates the extremely powerful potential of CMR 4D Flow in the management of complex congenital anomalies.
Mahmoud HM, Hosny M, Philip P, et al., 2016, An interatrial tunnel: a rare form of atrial septal defects., Echocardiography, Vol: 33, Pages: 1781-1784
Atrial septal defects (ASDs) account for approximately 6%-10% of congenital heart defects. The well-known types of atrial septal communications are the ostium secundum, ostium primum, sinus venosus types, and coronary sinus defects. A 50-year-old female was referred for TEE for better assessment of MR severity and mechanism. 2D/3D-TEE showed a rare combination of different abnormalities; bi-leaflet mitral valve prolapse, cleft P2, cor triatriatum sinister, and a tunnel-shaped IAS communication. To the best of our knowledge, this is a very rare case with a rare form of atrial septal defect that was not described before. We named this defect an interatrial tunnel.
Hassan M, Said K, Rizk H, et al., 2016, Segmental peri-coronary epicardial adipose tissue volume and coronary plaque characteristics., Eur Heart J Cardiovasc Imaging, Vol: 17, Pages: 1169-1177
AIMS: Epicardial adipose tissue (EAT) has been proposed to modulate underlying coronary plaque features. The study aimed to determine the relation between segmental EAT (sEAT) volume, assessed by cardiac magnetic resonance (CMR), and underlying coronary plaque characteristics, as estimated by multidetector computed tomography (CT) (MDCT). METHODS AND RESULTS: The study included 32 male patients with stable angina pectoris and 11 age-matched healthy controls. For each CAD patient, sEAT volume around 8 coronary segments (3 in left anterior descending artery, 3 in right coronary artery, and 2 in left circumflex artery) was quantified by CMR. By MDCT, plaques in each coronary segment were characterized in terms of plaque volume, type, CT attenuation, and severity of luminal stenosis. Serum levels of adipokines were measured. Total EAT volume was significantly higher in CAD patients than in control group. Serum resistin showed significant correlation with EAT volume (r = 0.69, P < 0.001). Analysis of 256 coronary segments showed larger sEAT volume with increasing luminal stenosis of the corresponding segment (mild: 8.2 cm(3); moderate: 11 cm(3); severe: 11.8 cm(3), P < 0.001). sEAT volume was larger in segments with mixed than those with calcified or non-calcified plaques (12.1 vs. 10.2 vs. 9.5 cm(3), respectively, P = 0.015). sEAT volume was larger in segments with low CT attenuation non-calcified plaques compared with non-calcified plaques with CT attenuation >30 HU (10.5 vs. 8.2 mm(3), P < 0.001). CONCLUSION: Peri-coronary epicardial adipose tissue volume is significantly associated with the extent and severity of coronary atherosclerosis and may be a determinant of plaque vulnerability.
Liberski A, Ayad N, Wojciechowska D, et al., 2016, Knitting for heart valve tissue engineering., Glob Cardiol Sci Pract, Vol: 2016, ISSN: 2305-7823
Knitting is a versatile technology which offers a large portfolio of products and solutions of interest in heart valve (HV) tissue engineering (TE). One of the main advantages of knitting is its ability to construct complex shapes and structures by precisely assembling the yarns in the desired position. With this in mind, knitting could be employed to construct a HV scaffold that closely resembles the authentic valve. This has the potential to reproduce the anisotropic structure that is characteristic of the heart valve with the yarns, in particular the 3-layered architecture of the leaflets. These yarns can provide oriented growth of cells lengthwise and consequently enable the deposition of extracellular matrix (ECM) proteins in an oriented manner. This technique, therefore, has a potential to provide a functional knitted scaffold, but to achieve that textile engineers need to gain a basic understanding of structural and mechanical aspects of the heart valve and in addition, tissue engineers must acquire the knowledge of tools and capacities that are essential in knitting technology. The aim of this review is to provide a platform to consolidate these two fields as well as to enable an efficient communication and cooperation among these two research areas.
Mahmoud HM, Walley H, Hosny H, et al., 2016, Three-dimensional transesophageal echocardiography incremental value in a rare case of a bileaflet tricuspid valve., Echocardiography, Vol: 33, Pages: 1438-1440
Detailed assessment of the tricuspid valve using two-dimensional echocardiography is always challenging, as only two of three leaflets can be seen at a time. Three-dimensional echocardiography can provide the enface view of the tricuspid valve that allows simultaneous visualization of all of the three leaflets. In a 42-year-old male patient scheduled for pulmonary endarterectomy, 3DTEE showed that the tricuspid valve is bileaflet, with one septal and another lateral leaflet. There were two commissures, one of them is anteriorly positioned and the other one is posterior. Our findings were confirmed intra-operatively by direct surgical visualization of the tricuspid valve.
Danial JSH, Aguib Y, Yacoub MH, 2016, Advanced fluorescence microscopy techniques for the life sciences, Global Cardiology Science & Practice, Vol: 2016, ISSN: 2305-7823
The development of super-resolved fluorescence microscopy, for which the Nobel Prize was awarded in 2014, has been a topic of interest to physicists and biologists alike. It is inevitable that numerous questions in biomedical research cannot be answered by means other than direct observation. In this review, advances to fluorescence microscopy are covered in a widely accessible fashion to facilitate its use in decisions related to its acquisition and utilization in biomedical research.
Spadotto V, Voges I, Kilner PJ, et al., 2016, Juxtaposition of the atrial appendages: A nidus for thrombus in atriopulmonary Fontan?, Global Cardiology Science & Practice, Vol: 2016, ISSN: 2305-7823
Juxtaposition of atrial appendages is a rare cardiac congenital anomaly, usually associated with other cardiac malformations. Until now, it has not been linked to any significant clinical implications. We report cardiovascular magnetic resonance (CMR) findings of two adult patients who underwent atriopulmonary Fontan operation in the setting of left juxtaposition of the atrial appendages. The patients were in sinus rhythm at the time of the CMR study. Both patients had episodes of sustained atrial tachyarrhythmia requiring electrical cardioversion and were anticoagulated with warfarin with target INR 2-3. CMR images showed a thrombus located in the enlarged and juxtaposed right appendage in both patients. Blood flow frequently appears slow or sluggish in the dilated right atrium following atriopulmonary Fontan surgery. In addition, cine CMR suggested that blood flow reaches very low velocities in the massively dilated juxtaposed right atrial appendage cul-de-sac, thus potentially creating a substrate for clot formation. These findings propose that juxtaposed atrial appendages in atriopulmonary Fontan is an additional risk factor for clot formation, specifically in the dilated right atrial appendage on the left side juxtaposed with the left atrial appendage and that prophylactic anticoagulation is highly justified in these patients.
Krishnamoorthy N, Gajendrarao P, Olivotto I, et al., 2016, Impact of disease-causing mutations on inter-domain interactions in cMyBP-C: a steered molecular dynamics study, JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, Vol: 35, Pages: 1916-1922, ISSN: 0739-1102
Remenyi B, ElGuindy A, Smith CS, et al., 2016, Erratum: Valvular heart disease 3. Valvular aspects of rheumatic heart disease. (Lancet (2016) 387 (1335-1346)), The Lancet, Vol: 387, ISSN: 0140-6736
Lee S, Aguib H, Chapron J, et al., 2016, Spatial Orientation and Morphology of the Pulmonary Artery: Relevance to Optimising Design and Positioning of a Continuous Pressure Monitoring Device, Journal of Cardiovascular Translational Research, Vol: 9, Pages: 239-248, ISSN: 1937-5387
Personalised treatment of heart disease requires an understanding of the patient-specific characteristics,which can vary over time. A newly developed implantable surface acoustic wave pressure sensor, capable ofcontinuous monitoring of the left ventricle filling pressure, is a novel device for personalised management ofpatients with heart disease. However, a one-size-fits-all approach to device sizing will affect its positioningwithin the pulmonary artery and its relationship to the interrogating device on the chest wall on a patientspecificlevel. In this paper, we analyse the spatial orientation and morphology of the pulmonary artery and itsmain branches in patients who could benefit from the device and normal controls. The results could optimisethe design of the sensor, its stent, and importantly its placement, ensuring long-term monitoring in patientgroups.
Torii R, Parker KH, Yacoub MH, 2016, Importance of Stress Mapping of Aortic Wall in Aortic Valve Disease., Journal of the American College of Cardiology, Vol: 67, Pages: 1755-1756, ISSN: 1558-3597
ElMaghawry M, Brugada J, Yacoub M, 2016, Disabling Palpitations in an Adolescent., JAMA Cardiol, Vol: 1, Pages: 107-108
Liberski A, Latif N, Raynaud C, et al., 2016, Alginate for cardiac regeneration: From seaweed to clinical trials., Glob Cardiol Sci Pract, Vol: 2016, ISSN: 2305-7823
Heart failure is a growing endemic in the aging Western population with a prevalence of over 20 million people worldwide1. Existing heart failure therapies are unable to reverse heart failure and do not address its fundamental cause, the loss of cardiomyocytes2. In order to induce myocardial regeneration for the myocardium and the heart valve, facilitate self-repair, improve tissue salvage, reduce or reverse the adverse-remodeling and ultimately achieve long-term functional stabilization and improvement in the heart function, novel strategies for therapeutic regeneration are being developed which are aiming to compensate for the insufficient and low intrinsic regenerative ability of the adult heart3. Similarly, valve replacement with mechanical or biological substitutes meets numerous hurdles. New approaches using multicellular approaches and new material are extensively studied. Most of those strategies depend on biomaterials that help to achieve functional integrated vasculogenesis and myogenesis in the heart/tissue. Especially for failed heart valve function a number of therapeutic approaches are common from corrective intervention to complete replacement4. However the complexity of the heart valve tissue and its high physical exposure has led to a variety of approaches, however therapeutic regeneration needs to be established. Beside other approaches alginate has been identified as one building block to achieve therapeutic regeneration. Alginate is a versatile and adaptable biomaterial that has found numerous biomedical applications which include wound healing, drug delivery and tissue engineering. Due to its biologically favorable properties including the ease of gelation and its biocompatibility, alginate-based hydrogels have been considered a particularly attractive material for the application in cardiac regeneration and valve replacement techniques. Here, we review current applications of alginate in cardiac regeneration as well as perspectives for the algi
Remenyi B, ElGuindy A, Smith SC, et al., 2016, Valvular heart disease 3 Valvular aspects of rheumatic heart disease, LANCET, Vol: 387, Pages: 1335-1346, ISSN: 0140-6736
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- Citations: 78
Mohamed NA, Ahmetaj-Shala B, Duluc L, et al., 2016, A New NO-Releasing Nanoformulation for the Treatment of Pulmonary Arterial Hypertension., Journal of Cardiovascular Translational Research, Vol: 9, Pages: 162-164, ISSN: 1937-5395
Pulmonary arterial hypertension (PAH) is a chronic and progressive disease which continues to carry an unacceptably high mortality and morbidity. The nitric oxide (NO) pathway has been implicated in the pathophysiology and progression of the disease. Its extremely short half-life and systemic effects have hampered the clinical use of NO in PAH. In an attempt to circumvent these major limitations, we have developed a new NO-nanomedicine formulation. The formulation was based on hydrogel-like polymeric composite NO-releasing nanoparticles (NO-RP). The kinetics of NO release from the NO-RP showed a peak at about 120 min followed by a sustained release for over 8 h. The NO-RP did not affect the viability or inflammation responses of endothelial cells. The NO-RP produced concentration-dependent relaxations of pulmonary arteries in mice with PAH induced by hypoxia. In conclusion, NO-RP drugs could considerably enhance the therapeutic potential of NO therapy for PAH.
Mongkoldhumrongkul N, Yacoub MH, Chester AH, 2016, Valve Endothelial Cells - Not Just Any Old Endothelial Cells, Current Vascular Pharmacology, Vol: 14, Pages: 146-154, ISSN: 1875-6212
Heart valves are sophisticated cellularised structures that perform a complex series of dynamic functions during each cardiac cycle. The endothelial cells (ECs) that cover both surfaces of the valve, play an important role in ensuring that the valve functions are in an optimal manner. They are also postulated to protect the valve against calcific disease. These functions include a role in embryonic development, regulation of cellular attachment, modulation of the mechanical properties of the valve, prevention of valve interstitial cell differentiation into pathological cell phenotypes and regulation of the valve extracellular matrix. It is believed that valve endothelial cells (VECs) are a specialised population of ECs which have a distinctive range of properties not seen elsewhere in the vasculature. This allows them to function in a unique haemodynamic environment. Each surface of the valve is exposed to vastly different patterns of blood flow and levels of shear stress, resulting in further specialisation of the VECs on the aortic and ventricular surfaces of the valve. This review will examine the role of VECs on either surface of the valve and demonstrate how they contribute to the function and durability of heart valves.
Kutryb-Zajac B, Yuen AHY, Khalpey Z, et al., 2016, Nucleotide Catabolism on the Surface of Aortic Valve Xenografts; Effects of Different Decellularization Strategies, Journal of Cardiovascular Translational Research, Vol: 9, Pages: 119-126, ISSN: 1937-5395
Extracellular nucleotide metabolism controls thrombosis and inflammation and may affect degeneration and calcification of aortic valve prostheses. We evaluated the effect of different decellularization strategies on enzyme activities involved in extracellular nucleotide metabolism. Porcine valves were tested intact or decellularized either by detergent treatment or hypotonic lysis and nuclease digestion. The rates of ATP hydrolysis, AMP hydrolysis, and adenosine deamination were estimated by incubation of aorta or valve leaflet sections with substrates followed by HPLC analysis. We demonstrated relatively high activities of ecto-enzymes on porcine valve as compared to the aortic wall. Hypotonic lysis/nuclease digestion preserved >80 % of ATP and AMP hydrolytic activity but reduced adenosine deamination to <10 %. Detergent decellularization completely removed (<5 %) all these activities. These results demonstrate high intensity of extracellular nucleotide metabolism on valve surface and indicate that various valve decellularization techniques differently affect ecto-enzyme activities that could be important in the development of improved valve prostheses.
Dokainish H, Teo K, Zhu J, et al., 2016, Heart Failure in Africa, Asia, the Middle East and South America: The INTER-CHF study, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 204, Pages: 133-141, ISSN: 0167-5273
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- Citations: 91
Hassan M, Aguib Y, Yacoub M, 2016, Molecular mechanisms of cardiovascular benefits of exercise: Running for cover from heart disease, Global Cardiology Science and Practice, Vol: 2016
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Murphy O, Bahmanyar MR, McLeod CN, et al., 2016, Beyond RF ablation other uses for RF within the body, Pages: 1362-1364
The use of high frequencies within the body is commonplace for treatment and imaging, but, other than a few examples very little exists in terms of RF sensors and for communication deep into the body. This paper will give an overview of an RF powered implantable blood pressure sensor for continuous monitoring and in doing so demonstrate the use of RF within the body.
El-Hamamsy I, Yacoub MH, 2016, Towards More Personalized Surgical Indications for Thoracic Aortic Dilatation: Are We There Yet?, Canadian Journal of Cardiology, Vol: 32, Pages: 4-7, ISSN: 1916-7075
Thoracic aortic aneurysms remain an important cause of death in the general population. The key to improving patient prognosis with thoracic aortic dilatation lies in early identification and tailored management strategies. Advances in the understanding of the molecular mechanisms of aneurysm formation, the natural history of disease, and clinical risk factors have led to significant improvements in patient management and overall outcomes. In the past decade, identification of the genetic basis of disease, together with wider availability of molecular testing, ushered in a new era for a tailored approach to the management of patients with thoracic aortic aneurysms. In this viewpoint, we explore these various iterative steps and future challenges.
Nulu S, Neely RC, Tawakol Z, et al., 2016, African leaders take action on RHD: The 4th All-Africa Workshop on Acute Rheumatic Fever and Rheumatic Heart Disease and African Union RHD Communiqué
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Murphy O, Bahmanyar MR, McLeod CN, et al., 2016, Beyond RF Ablation Other uses for RF within the body., 11th European Microwave Integrated Circuits Conference (EuMIC), Publisher: IEEE, Pages: 433-435
Levine RA, Hagege AA, Judge DP, et al., 2015, Mitral valve disease morphology and mechanisms, NATURE REVIEWS CARDIOLOGY, Vol: 12, Pages: 689-710, ISSN: 1759-5002
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- Citations: 221
Balbaa A, ElGuindy A, Pericak D, et al., 2015, An evaluation of secondary prophylaxis for rheumatic heart disease in rural Egypt., Global Cardiology Science and Practice, Vol: 2015, Pages: 40-40, ISSN: 2305-7823
BACKGROUND: Although essentially disappeared from the industrialized world, rheumatic heart disease (RHD) is still prevalent in developing countries, with 300,000 new cases identified each year. In Aswan, Egypt, RHD affects about 2.3% of children with over 90% of the cases being subclinical. Secondary prophylaxis has proved to be an effective method of preventing the progression of RHD. However, its efficacy is limited by low patient adherence. A systematic, generalizable tool is necessary to outline, and ultimately address these barriers. METHODS: A 43-item semi-structured questionnaire was developed based on the three domains outlined by Fishbein (capability, intention, and health care barriers). A preliminary evaluation of the barriers to RHD prophylaxis use in Aswan, Egypt was carried out as a pilot study using this tool. Participants were local school children diagnosed with RHD or flagged as high-risk (as per a set of echocardiographic criteria developed by the Aswan Heart Centre) through a previous screening program of randomly selected 3,062 school children in Aswan. RESULTS: 29 patients were interviewed (65.5% adherent to RHD prophylaxis). Compared to non-adherent patients, adherent patients had better understanding of the disease (68.4% versus 20% in the non-adherent group, p = 0.021), and were more aware of the consequences of missing prophylaxis doses (79% versus 40% of non-adherent patients, p = 0.005). Furthermore, 90% of non-adherent patients consciously choose to miss injection appointments (as compared to 31.6% of adherent patients, p = 0.005). Clinic wait time was the most frequently reported deterrent for both groups. CONCLUSION: A standardized tool that systematically outlines barriers to prophylaxis is a necessary first step to improving adherence to penicillin. Although individually developed tools exist for specific populations, a generalizable tool that takes into account the demographic and cultural differences
Allouba MH, ElGuindy AM, Krishnamoorthy N, et al., 2015, NaNog: A pluripotency homeobox (master) molecule., Global Cardiology Science and Practice, Vol: 2015, Pages: 36-36, ISSN: 2305-7823
One of the most intriguing aspects of cell biology is the state of pluripotency, where the cell is capable of self-renewal for as many times as deemed "necessary", then at a specified time can differentiate into any type of cell. This fundamental process is required during organogenesis in foetal life and importantly during tissue repair in health and disease. Pluripotency is very tightly regulated, as any dysregulation can result in congenital defects, inability to repair damage, or cancer. Fuelled by the relatively recent interest in stem cell biology and tissue regeneration, the molecules implicated in regulating pluripotency have been the subject of extensive research. One of the important molecules involved in pluripotency, is NaNog, the subject of this article.
Fox K, Haxby E, Fox I, et al., 2015, How should the UK pioneer innovative and untested procedures?, LANCET, Vol: 386, Pages: 1446-1446, ISSN: 0140-6736
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