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Genetic Determinants Of Diabetes

Genetic Determinants Of Type 2 Diabetes Mellitus.

Genetic Determinants Of Type 2 Diabetes Mellitus.

Genetic determinants of type 2 diabetes mellitus. (1)John P. Robarts Research Institute, London, Ontario, Canada N6A 5K8. Type 2 diabetes refers to a group of disparate metabolic diseases, which aretypically characterized by insulin resistance in peripheral tissues, togetherwith impaired insulin secretion from pancreatic beta-cells. The complexity oftype 2 diabetes is related to factors such as genetic heterogeneity, interactionsbetween genes, and the modulating role played by the environment. Recent progresshas included defining the molecular basis of monogenic forms of type 2 diabetes, such as familial partial lipodystrophy and the subtypes of maturity-onsetdiabetes of the young (MODY), and also the identification of chromosomal regions that may harbor type 2 diabetes susceptibility genes. Many common variants infunctional and positional candidate genes, including ADRB3, PPARG, ENPP1, andCAPN10, have also been studied for their possible role as determinants of type 2 diabetes, with varying levels of agreement between studies. The availability of arelatively complete sequence of the human genome will increase the amount ofgenetic information that can be used to evaluate hypotheses for the genetic basisof type 2 diabetes. To make sense of human type 2 diabetes in the post-genomicera, it is essential to have well-defined phenotypes in addition to sufficientnumbers of individuals with the appropriate pedigree structure from familiesand/or communities. Continue reading >>

Genetic And Non-genetic Determinants Of Drug Response In Type 2 Diabetes

Genetic And Non-genetic Determinants Of Drug Response In Type 2 Diabetes

Genetic and non-genetic determinants of drug response in type 2 diabetes Genetic and non-genetic determinants of drug response in type 2 diabetes Student thesis: Doctoral Thesis Doctor of Medicine Background:Approximately 415 million people live with diabetes worldwide. Type 2 diabetes(T2D) accounts for 85%95% of the cases. Despite the availability of severaldrugs, considerable interindividual variation in response to medicationsresults in unnecessary treatment failure. In addition to non-genetic factors, geneticfactors are thought to contribute to such variability. Aim: This thesisattempts to investigate genetic and non-genetic factors underlying thevariability in response to commonly used drugs in T2D. Methods:We assessed drug response as efficacy and/or adverse effect following treatmentusing data gathered from medical records mainly from the Diabetes Research forPatient Stratification (DIRECT) consortium and the Genetics of Diabetes Auditand Research Tayside Study (GoDARTS). Genetic data was obtained usingchip-based arrays followed by imputation and TaqMan genotyping. Subsequentcandidate gene and genome wide association (GWAS) analyses were conducted usinglinear and logistic regressions followed by meta-analyses. In addition,downstream rare variant burden test and pathway analyses were performed. Results:We showed robust association of metformin use with fasting glucagon likepeptide-1 (GLP-1) levels in diabetic and non-diabetic subjects. Gastrointestinal(GI) irritation is the most common side effect of metformin. Concomitantadministration of metformin with gut metformin transporter inhibiting drugssuch as tricyclic antidepressants, proton pump inhibitors and codeine increasedthe odds of GI intolerance. Moreover we showed association of the G allele atrs3889348-SLC2 Continue reading >>

Genetic Determinants Of Serum 25-hydroxyvitamin D Concentration During Pregnancy And Type 1 Diabetes In The Child

Genetic Determinants Of Serum 25-hydroxyvitamin D Concentration During Pregnancy And Type 1 Diabetes In The Child

Genetic determinants of serum 25-hydroxyvitamin D concentration during pregnancy and type 1 diabetes in the child Roles Conceptualization, Data curation, Investigation, Resources, Writing original draft, Writing review & editing Affiliations Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom, University of Essex, Essex, United Kingdom Roles Conceptualization, Data curation, Methodology, Resources, Visualization, Writing original draft, Writing review & editing Affiliation Genomics and Biomarkers Unit, National Institute for Health and Welfare, Helsinki, Finland Roles Conceptualization, Formal analysis, Methodology, Resources, Visualization, Writing review & editing Affiliations Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland, Folkhlsan Institute of Genetics, Folkhlsan Research Center, Helsinki, Finland, Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland, Research Program Unit, Diabetes and Obesity, Helsinki, Finland Roles Data curation, Investigation, Resources, Writing review & editing Affiliation Vaccination Programme Unit, National Institute for Health and Welfare, Helsinki, Finland Roles Data curation, Investigation, Resources, Writing review & editing Affiliation Translational Cancer Biology Research Program, University of Helsinki, Helsinki, Finland Roles Conceptualization, Investigation, Methodology, Resources, Writing review & editing Affiliation Impact Assessment Unit, National Institute for Health and Welfare, Oulu, Finland Roles Conceptualization, Funding acquisition, Methodology, Project administration, Supervision, Writing review & editing Affiliation Department of Food and Environ Continue reading >>

Impact Of Common Genetic Determinants Of Hemoglobin A1c On Type 2 Diabetes Risk And Diagnosis In 1 Ancestrally Diverse Populations: A Transethnic Genome-wide Meta-analysis

Impact Of Common Genetic Determinants Of Hemoglobin A1c On Type 2 Diabetes Risk And Diagnosis In 1 Ancestrally Diverse Populations: A Transethnic Genome-wide Meta-analysis

Impact of Common Genetic Determinants of Hemoglobin A1c on Type 2 Diabetes Risk and Diagnosis in 1 Ancestrally Diverse Populations: A Transethnic Genome-Wide Meta-Analysis Wong, A; (2017) Impact of Common Genetic Determinants of Hemoglobin A1c on Type 2 Diabetes Risk and Diagnosis in 1 Ancestrally Diverse Populations: A Transethnic Genome-Wide Meta-Analysis. PLoS Medicine 10.1371/journal.pmed.1002383 . BACKGROUND: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes. METHODS AND FINDINGS Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassi Continue reading >>

Aspph | Bu Identifies Genetic Determinants Of Diabetes In African Americans

Aspph | Bu Identifies Genetic Determinants Of Diabetes In African Americans

BU Identifies Genetic Determinants of Diabetes in African Americans A new multi-ethnic study by an international team led by researchers from Boston University School of Public Health (BUSPH) and Massachusetts General Hospital has found that African Americans and white share some genetic determinants of Type 2 diabetes, while also carrying some unique genetic loci. The study, published online in the American Journal of Human Genetics , found that about half of gene variants identified in people of European ancestry were shared by African Americans, suggesting that genetic determinants of human glucose regulation are more similar than different across human populations. The study also identified two new genetic variants, bringing to 56 the number of Type 2 diabetes fasting-glucose and fasting-insulin-associated loci. Dr. Ching-Ti Liu, a lead author and associate professor of biostatistics at BUSPH, said the study is an important step to illuminating genetic variation underlying type 2 diabetes, which affects more than 400 million people globally. Racial and ethnic differences in diabetes have been understudied, Dr. Liu said. We feel strongly that the trans-ethnic approach, combined with the genomic annotation information we used, will lead the way forward to understand the implications of the genetic variations underlying type 2 diabetes and other complex disorders. To read more about the study, go to: Continue reading >>

Dr Raymond Noordam, Genetic Determinants For Insulin-dependent Type 2 Diabetes Mellitus

Dr Raymond Noordam, Genetic Determinants For Insulin-dependent Type 2 Diabetes Mellitus

Dr Raymond Noordam, Genetic determinants for insulin-dependent type 2 diabetes mellitus Dr Raymond Noordam, Genetic determinants for insulin-dependent type 2 diabetes mellitus Principal Investigator: Dr Raymond Noordam Tags: 22474 , diabetes , genetics , insulin-depedent 1a: Type 2 diabetes mellitus (T2D) is a heterogeneous disease caused by different mechanisms, including insulin resistance and pancreatic malfunction. Of the patients diagnosed with T2D, a fair amount of the patients requires insulin analogs shortly (e.g., within 1 year) after diagnoses, which is indicative of a major role for pancreatic malfunction already at the moment of diagnosis. Malfunction of the pancreas results in an insulin-dependent T2D phenotype. In this project, we will investigate genetic determinants for insulin-dependent type 2 diabetes mellitus as defined by the use of insulin analogs within 1 year after diagnosis. 1b: The prevalence and incidence of type 2 diabetes mellitus is increasing. After diagnosis, patients with type 2 diabetes are often prescribed oral glucose-lowering drugs, but treatment response is often insufficient or associated with serious adverse drug reactions. A better understanding of the pathophysiological mechanisms present in the patient is pivotal to select the right treatment with a high probability of success. In the proposed project, we will use genetic analyses to determine whether there are different pathophysiological mechanisms involved in patients that do or do not start insulin analogs shortly after diagnosis of type 2 diabetes mellitus. 1c: We will conduct a Genome-Wide association study on the following outcomes: Type 2 diabetes mellitus; those that start insulin analogs shortly after diagnosis Type 2 diabetes mellitus; those that dont start insulin a Continue reading >>

Genetic Determinants Of Type 2 Diabetes Mellitus: Lessons Learned From Family Studies.

Genetic Determinants Of Type 2 Diabetes Mellitus: Lessons Learned From Family Studies.

Genetic determinants of type 2 diabetes mellitus: lessons learned from family studies. Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France. Non insulin dependent diabetes mellitus (Type 2) is a multifactorial disease, with a polygenic inheritance and environmental factors contributing to its clinical expression. The search for the genetic determinants of Type 2 diabetes began when several genes involved in the mechanisms of insulin secretion or action were cloned, localized in the human genome, and when informative polymorphisms were described within or in the vicinity of these genes. It then became possible to compare, in groups of patients and normoglycaemic controls from various populations, the frequency of the different alleles of polymorphic markers of various candidate genes (e.g. insulin, insulin receptor, glucose transporters). The conflicting results observed in these studies can be ascribed to the small size of the population samples, to the genetic heterogeneity of Type 2 diabetes mellitus, but also to the methodology used therein. Indeed, these studies searched for a correlation between the frequency of certain alleles or genotypes and the phenotype of diabetes (studies of associations in affected populations compared to healthy controls). However in order to attribute to a gene the responsibility for a disease it is necessary to demonstrate the cotransmission in affected kindreds of a morbid allele of the gene along with the disease (familial or linkage analysis). The aim of this review is to summarize the results of family studies of Type 2 diabetes and Maturity Onset Diabetes of the Young (MODY), particularly with concern to the mutations described in candidate genes, and the implication of glucokinase in these disorders. Continue reading >>

Genetic Determinants Of Type 2 Diabetes.

Genetic Determinants Of Type 2 Diabetes.

Institute of Biology-CNRS 8090, Institut Pasteur de Lille, France. Hyperglycemia of type 2 diabetes mellitus (T2DM) results from a complex interplay of genetic and environmental factors that influence a number of intermediate traits (e.g., beta-cell mass, insulin secretion, insulin action, fat distribution, obesity). The primary biochemical events leading to diabetes are still unknown in most cases. Although several monogenic forms of diabetes have been identified, T2DM seems to be a polygenic disorder in the majority of cases. T2DM is probably also multigenic, meaning that many different combinations of gene defects may exist among diabetic patients. Significant results were obtained in the identification of the genetic determinants of monogenic forms of diabetes with young age of onset. However, despite the evidence for a strong genetic background, little of the genetic risk factors for the more-common forms of polygenic T2DM are known to date. The goal of this chapter is to summarize and discuss the significant results of recent literature on the genetics of both the monogenic and polygenic forms of T2DM. Continue reading >>

Genetic Determinants Of Lipoprotein (a) Levels Related To Risk Of Atherosclerosis

Genetic Determinants Of Lipoprotein (a) Levels Related To Risk Of Atherosclerosis

General Research Subject: Both Type 1 and Type 2 Diabetes Focus: Complications, Complications\Macrovascular-Atherosclerotic CVD and Human Diabetes, Complications\Diabetic Dyslipidemia, Genetics, Genetics\Type 2 Diabetes The incidence of cardiovascular disease (CVD) in patients with diabetes is markedly increased. A high cholesterol level in the blood is an important independent risk factor for atherosclerosis, the underlying cause of CVD. Recent evidence from large cohorts suggest that a particular protein that is associated with cholesterol, called Lp(a) may be an important determinant of coronary heart disease and stroke. Lp(a) levels are genetically determined; however, the specific genes involved are not completely known. Moreover, no practical method for pharmacologic lowering of Lp(a) levels is currently available. The objective of this proposal is to define the genetic architecture of Lp(a) to glean insights into mechanisms of Lp(a) regulation in patients with diabetes. They propose to use a multi-pronged high-throughput genomics approach to identify specific gene variations that influence Lp(a) levels. They will sequence genes on two chromosomal regions that they have previously found to be associated with Lp(a) levels in the Old Order Amish. The gene variations they identify will be prioritized and the most likely functional variations further tested to see if they are associated with changes in the expression of genes, Lp(a) levels, and atherosclerosis in patients. Identification of the genes that influence Lp(a) levels may lead to the design of novel therapeutic strategies to lower Lp(a) levels to prevent or treat CVD in patients with diabetes. What area of diabetes research does your project cover? What role will this particular project play in preventing, Continue reading >>

Genetic Determinants Of Type 1 Diabetes

Genetic Determinants Of Type 1 Diabetes

Medicine Endocrinology and Metabolism "Type 1 Diabetes - Pathogenesis, Genetics and Immunotherapy" , book edited by David Wagner, ISBN 978-953-307-362-0, Published: November 25, 2011 under CC BY 3.0 license . The Author(s). Figure 1. Diagrammatic presentation of effects of cytokines gene polymorphisms in T1D.This schematic diagram explains the possible effects of cytokines in the initiation triggering of T1D by signals from either environmental factors A or immunogenic factors B or both. Release of IL-6 would change the counterbalance between TH1/TH2 C cytokines level. Increase level of TH1, IFN-, cause the cytotoxic process of break down of -cell by CD8. As a result of deviation of cytokine cross regulation to TH1 dominance TH3 lymphocyte subset produce immunosuppressive cytokines, TGF- 1, however, due to genetic malfunction this cytokines are proved not to be able to bring TH1/TH2 back to normal position, D. Which will lead to the death of pancreatic cell. This is a simplified schematic descriptions of the impact of cytokines in the pathogenesis of T1D, for detail please refer to Jahromi et al 2000, 2000a and 2010. [1] Salmaniya Medical Complex, Ministry of Health,, Kingdom of Bahrain Type 1 diabetes is (T1D) is an autoimmune disorder characterized by the T-cell-mediated destruction of the insulin-secreting cells of the pancreatic islet of Langerhans. T1D is heterogeneous in terms of age at diabetes development with as many adults developing the disorder as children( Barnett et al 1981 ). Genetic susceptibility is dependent on the degree of genetic identity with the proband, and the risk of diabetes in families has a non-linear correlation with the number of alleles shared with the proband. The highest risk is naturally observed in monozygotic twins (100% sharing) fo Continue reading >>

Update On Genetic Determinants Of Type1 Diabetes

Update On Genetic Determinants Of Type1 Diabetes

1Pediatric Endocrinology Unit, Cliniques Universitaires Saint Luc, Belgium 2Pôle PEDI, Institut de Recherche Expérimentale et Clinique", Université Catholique de Louvain, Belgium Citation: Lysy PA (2014) Update on Genetic Determinants of Type 1 Diabetes. J Mol Genet Med 8:126. doi:10.4172/1747-0862.1000126 Copyright: © 2014 PALysy, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. Visit for more related articles at Journal of Molecular and Genetic Medicine Abstract Type 1 diabetes (T1D) results from a progressive destruction of insulin-secreting β cells with consecutive life-long dependence to exogenous insulin. Avoidance of end-stage β-cell mass destruction through primary and secondary prevention strategies requires understanding of initial molecular events leading to insulinopenia. Although autoimmune dysregulation is predominant in T1D, environmental and genetic predisposing factors have been identified and partly account for the heterogeneity of the disease. The use of patient databases and the development of new technologies for genetic screening will help to identify at-risk individuals in the general population or in families with affected siblings. Here we discuss the latest developments in the identification of genetic determinants of T1D and their use for evaluation of disease risk. Keywords Type 1 Diabetes; Hyperglycemia; Insulinopenia; Autoimmune disease; Proteiform disease Introduction Type 1 diabetes (T1D) is characterized by a progressive destruction of insulin-secreting β cells that results in the development of chronic hyperglycemia and ketone body form Continue reading >>

Genetic Determinants Of Diabetes And Atherosclerosis

Genetic Determinants Of Diabetes And Atherosclerosis

, Volume 4, Issue3 , pp 193198 | Cite as Genetic determinants of diabetes and atherosclerosis Common risk factors for type 2 diabetes and cardiovascular disease are suspected because of the higher than expected prevalence of cardiovascular disease in individuals with newly diagnosed type 2 diabetes and in nondiabetic individuals with impaired glucose tolerance. Some of these risk factors may be genetic in origin. The risk of diabetes and cardiovascular disease may be linked through common pathways, including insulin resistance and/or inflammation. In this review, we describe the rationale for proposing these as common mechanisms affecting both diabetes and cardiovascular risk, and we then summarize the available evidence suggesting that common genes within these pathways have pleiotropic effects influencing susceptibility to both diseases. Insulin ResistanceArterioscler Thromb Vasc BiolInsulin Resistance SyndromeCardiovascular Health StudyStrong Heart Study These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves. This is a preview of subscription content, log in to check access Unable to display preview. Download preview PDF. Mitchell BD: Macrovascular disease in diabetes. In Diabetes: Clinical Science in Practice. Edited by Leslie RDG, Robbins DC. Cambridge, UK: Cambridge University Press; 1995:222236. Google Scholar Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M: Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998, 339:229234. PubMed CrossRef Google Scholar Jarrett RJ: Type 2 (non-insulin-dependent) diabetes mellitus and coronary heart disease-chicken, Continue reading >>

Genetic Determinants (of Subtypes) Of Type 2 Diabetes Mellitus In The Uk Biobank

Genetic Determinants (of Subtypes) Of Type 2 Diabetes Mellitus In The Uk Biobank

Genetic determinants (of subtypes) of type 2 diabetes mellitus in the UK Biobank The quest to identify genetic markers for type 2 diabetes mellitus is complicated as type 2 diabetes mellitus is a heterogeneous disease condition (Groop et al, 2014, Mol Cell Endocrinology). Under physiological circumstances, increased peripheral insulin resistance is compensated by increased insulin secretion by the pancreas. However, when the pancreas is not able anymore to deliver the higher demands of insulin, glucose levels will start to rise and type 2 diabetes mellitus will eventually be diagnosed. The compensatory capacity of the pancreas varies among individuals. Consequently, individuals diagnosed with type 2 diabetes mellitus may differ in the extent to which their disease phenotype is dependent on defects in insulin secretion or insulin resistance. In patients with type 2 diabetes mellitus in whom disease pathogenesis is more critically dependent on defects in insulin secretion, conventional (first-line) treatment will be less able to show a sufficient response. We hypothesize that stratifying the type 2 diabetes mellitus phenotype according to the requirement of insulin soon after diagnosis will provide additional insights in the pathophysiological mechanisms of type 2 diabetes mellitus. Genome-wide association studies on both phenotypes will likely reveal specific loci for one of the two phenotypes. In addition, it has been described in the literature that the pathophysiological mechanisms are different for middle- and high-aged individuals (Lee et al, 2017, Diabetes Care). Notably, type 2 diabetes mellitus diagnosed at middle age might be predominantly caused by insulin resistance, whereas type 2 diabetes mellitus diagnosed at a higher age might be predominantly caused by e Continue reading >>

Genetic Determinants Of Diabetic Nephropathy: The Family Investigation Of Nephropathy And Diabetes (find)

Genetic Determinants Of Diabetic Nephropathy: The Family Investigation Of Nephropathy And Diabetes (find)

Genetic Determinants of Diabetic Nephropathy: The Family Investigation of Nephropathy and Diabetes (FIND) The Family Investigation of Nephropathy and Diabetes Research Group Correspondence to Dr. Robert C. Elston, Genetic Analysis and Data Coordinating Center, Family Investigation of Nephropathy and Diabetes, Case Western Reserve University, Department of Epidemiology and Biostatistics, MetroHealth Medical Center, 2500 MetroHealth Drive, Cleveland, OH 44109. Phone: 216-778-4526; Fax: 216-778-3280; ABSTRACT. Diabetes mellitus is the leading cause of ESRD in the United States. Family-based studies and segregation analyses suggest that inherited factors play a major role in susceptibility to diabetic renal complications, including albuminuria and chronic kidney failure. The Family Investigation of Nephropathy and Diabetes (FIND) study is a multicenter consortium established by the National Institute of Diabetes, Digestive and Kidney Diseases to identify the gene(s) responsible for diabetic nephropathy. Eight participating centers will enroll nearly 10,000 individuals by September 2004. Two independent strategies to detect causative genes will be used. These include family-based linkage analyses in African-American, American-Indian, Mexican-American, and European-American families (predominantly affected and discordant relative pair analyses) and mapping by admixture linkage disequilibrium (MALD) in African and Mexican Americans. Cell lines are being created from participants, and a repository containing stored urine and serum samples has been developed. This paper describes the enrollment criteria and methods used in FIND to allow for the detection of gene(s) predisposing to diabetic nephropathy. E-mail: [email protected] Diabetic nephropathy (DN) is the most Continue reading >>

Identifying Genetic Determinants Of Diabetes In African Americans

Identifying Genetic Determinants Of Diabetes In African Americans

Identifying Genetic Determinants of Diabetes in African Americans Posted on: June 28, 2016 Topics: Type 2 diabetes The global burden of type 2 diabetes is borne disproportionately by people of non-European ancestry, especially African Americans. But those racial and ethnic disparities have received little attention from genetics researchers. Now, a new multi-ethnic study by an international team, led by researchers from the School of Public Health and Massachusetts General Hospital, has found that African Americans and whites share some genetic determinants of Type 2 diabetes, while also carrying some unique genetic loci. The study, published online in the American Journal of Human Genetics , found that about half of gene variants identified in people of European ancestry were shared by African Americans, suggesting that genetic determinants of human glucose regulation are more similar than different across human populations. The study also identified two new genetic variants, bringing to 56 the number of Type 2 diabetes fasting-glucose and fasting-insulin-associated loci. Ching-Ti Liu, a lead author and associate professor of biostatistics, said the study is an important step to illuminating genetic variation underlying type 2 diabetes, which affects more than 400 million people globally. Racial and ethnic differences in diabetes have been understudied, Liu said. We feel strongly that the trans-ethnic approach, combined with the genomic annotation information we used, will lead the way forward to understand the implications of the genetic variations underlying type 2 diabetes and other complex disorders. Co-author James Meigs of Massachusetts General Hospital and Harvard Medical School said the research team assembled the largest-ever collection of genetic information Continue reading >>

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