New genomic technologies for the study of OA

Molecular Epidemiolog

Artrose; van diversiteit in moleculaire paden tot effectieve therapie op maat

Oratie uitgesproken door Prof.dr. I. Meulenbelt bij de aanvaarding van het ambt van hoogleraar op het gebied van Moleculaire Biologie van Artrose aan de Universiteit Leiden op vrijdag 19 januari 2018Oratie uitgesproken door Prof.dr. I. Meulenbelt bij de aanvaarding van het ambt van hoogleraar op het gebied van Moleculaire Biologie van Artrose aan de Universiteit Leiden op vrijdag 19 januari 2018LUMC / Geneeskunde Repositoriu

Summary of the OA biomarkers workshop 2010 – genetics and genomics: new targets in OA

SummaryOn November fourth and fifth 2010 a group of more than 100 international investigators gathered in Atlanta for the second Osteoarthritis (OA) Biomarkers Global Initiative workshop titled “Genetics and Genomics: New Targets in OA”. The first workshop took place in April 2009 and focused on in vitro (soluble) biomarkers whilst the third and final workshop will take place in 2012 and will focus on imaging biomarkers. The OA Research Society International (OARSI) has organized the workshops. In addition to OARSI, the National Institute of Arthritis, Musculoskeletal and Skin Diseases, the Arthritis Foundation, Amgen, Genzyme, the American Orthopaedic Society for Sports Medicine and Pfizer sponsored the second meeting. It was clear from this meeting that experiments in the genetics, epigenetics and genomics of OA, are yielding valuable insights into the etiology of this heterogeneous disease but that much still needs to be learnt. Combining genetic insights with conventional biomarkers and imaging modalities may provide scientists with the enhanced tools to understand this complex disease. With those tools in hand, clinicians and industry can develop protocols to ultimately improve patient care

Еліпсис – один із найважливіших шляхів поповнення складу мінімальних фразеологічних одиниць

Стаття присвячена актуальній науковій проблемі, пов'язаній із аналізом спеціального фрагмента фразеологічного корпусу української мови - мінімальним ідіомам. Описуються два види фразеологічного еліпсиса.Статья посвящена актуальной научной проблеме, связанной с анализом специального фрагмента фразеологического корпуса украинского языка - минимальным идиомам. Описываются два вида фразеологического элипсиса.The article is dedicated to the scientific actual problem, connected with the analysis of special fragment in phraseological structure of the Ukrainian language - minimal idioms. Two types of phraseological ellipsis described

Acute intoxications among humans and animals. National Poisons Information Centre. Annual Report, 2005-2006

Het Nationaal Vergiftigingen Informatie Centrum (NVIC) ontving in 2005 36.375 en in 2006 37.088 informatieverzoeken over acute intoxicaties van mensen en dieren. Deze informatievragen betroffen circa 50.000 blootstellingen aan lichaamsvreemde stoffen per jaar. Ruim de helft van deze intoxicaties betrof overdoseringen met geneesmiddelen. Het aantal vergiftigingen met pijnstillers die zonder recept verkrijgbaar zijn, zoals paracetamol en ibuprofen, is in 2005 en 2006 weer toegenomen. Daarnaast is bij volwassenen het aantal meldingen over melatonine de afgelopen jaren sterk gestegen, van 3 in 2001 naar 76 in 2006. Een relatief nieuw verschijnsel waar het NVIC in 2006 over geraadpleegd werd, waren de zogenaamde crofty-bommen: doe-het-zelfbommen gemaakt met gootsteenontstopper. Bij ontploffing van crofty-bommen en aanraking met de vloeistof, kunnen ernstige chemische letsels ontstaan aan huid en ogen. Het aantal meldingen over drugs is voor het eerst in jaren afgenomen, van 1.383 in 2005 naar 1.146 in 2006. Het aantal meldingen over amfetamine-intoxicaties is sinds 2005 echter sterk gestegen, van 31 in 2004 naar 114 in 2005 en 97 in 2006. Het aantal vergiftigingen met efedra is na 2004 met 57% afgenomen. De wetswijziging in 2004, waardoor efedra-bevattende producten uitsluitend nog als geneesmiddel mogen worden verhandeld, is hier mogelijk de oorzaak van. Nadat in november 2006 Alexander Litvinenko in Londen werd vergiftigd met radioactief polonium-210, heeft het Rijksinstituut voor Volksgezondheid en Milieu (RIVM) urinemonsters geanalyseerd van 11 mogelijk blootgestelde Nederlanders. Het NVIC heeft daarbij een actieve rol gespeeld in de opsporing van de betreffende Nederlanders en de medische beoordeling van de resultaten. Het persbericht over het RIVM onderzoek heeft veel media-aandacht getrokken, waardoor het NVIC 73 maal is geconsulteerd over het poloniumincident.In 2005 the National Poisons Information Centre (NVIC) received 36,375 enquiries and in 2006, 37,088, all on acute intoxications of humans and animals. These enquiries concerned about 50,000 exposures to chemical substances per year. More than half of these intoxications were due to a medication overdose. The number of intoxications due to over-the-counter painkillers, such as paracetamol and ibuprofen, increased again in 2005 and in 2006. In addition, the number of consultations on melatonin exposure in adults increased sharply the last few years, from 3 in 2001 to 76 in 2006. A relatively new phenomenon calling for NVIC consultation in 2006 were the so-called crofty bombs (do-it-yourself bombs made from caustic soda). Explosion of a crofty bomb and contact with the liquid can result in serious chemical injuries to skin and eyes. For the first time in years, the number of consultations on drugs decreased, from 1,383 in 2005 to 1,146 in 2006. However, the number of enquiries about intoxications with amphetamines increased sharply compared to 2004, from 31 in 2004 to 114 in 2005 and 97 in 2006. After 2004, the number of intoxications with ephedra decreased by 57%. The amendment of the law in 2004, stating that ephedra-containing products could, with immediate effect, only be marketed as medicinal products, may have induced this decrease. Following the poisoning of Alexander Litvinenko in London with radioactive polonium-210 in November 2006, the National Institute for Public Health and the Environment (RIVM) analysed urine samples from 11 Dutch citizens who had possibly been exposed. The NVIC played an active role here in tracing the people concerned and in the medical evaluation of the results. The press release on the RIVM study attracted considerable attention from the media, resulting in 73 enquiries to the NVIC for information on the polonium incident.Directie Publieke Gezondhei

High microsatellite and SNP genotyping success rate established in a large number of genomic DNA samples extracted from mouth swabs and genotypes

In this article, we present the genomic DNA yield and the microsatellite and single nucleotide polymorphism (SNP) genotyping success rates of genomic DNA extracted from a large number of mouth swab samples. In total, the median yield and quality was determined in 714 individuals and the success rates in 378,480 genotypings of 915 individuals. The median yield of genomic DNA per mouth swab was 4.1 μg (range 0.1-42.2 μg) and was not reduced when mouth swabs were stored for at least 21 months prior to extraction. A maximum of 20 mouth swabs is collected per participant. Mouth swab samples showed in, respectively, 89% for 390 microsatellites and 99% for 24 SNPs a genotyping success rate higher than 75%. A very low success rate of genotyping (0%-10%) was obtained for 3.2% of the 915 mouth swab samples using microsatellite markers. Only 0.005% of the mouth swab samples showed a genotyping success rate lower than 75% (range 58%-71 %) using SNPs. Our results show that mouth swabs can be easily collected, stored by our conditions for months prior to DNA extraction and result in high yield and high-quality DNA appropriate for genotyping with high success rate including whole genome searches using microsatellites or SNPs

Genetic influences on disordered eating behaviour are largely independent of body mass index.

Objective: Prior studies suggest eating disorders and related characteristics are moderately to substantially heritable. We are interested in identifying the genes underlying disordered eating behaviour (DEB), and want to know how much of the genetic influence underlying DEB is attributable to genetic influences on body mass index (BMI). Method: Bivariate analyses were performed, in adolescent twins and siblings, to estimate the genetic and environmental contributions for DEB, BMI, and their overlap. Results: Shared genetic risk factors explained the overlap between BMI and DEB (genetic correlation was 0.43 in women, 0.51 in men). DEB was highly heritable in women (

Clusters of biochemical markers are associated with radiographic subtypes of osteoarthritis (OA) in subject with familial OA at multiple sites. The GARP study

SummaryObjectiveTo assess the relationship of biochemical markers and radiographic signs of osteoarthritis (ROA) in the subjects with symptomatic osteoarthritis (OA) at multiple sites of the Genetics osteoARthritis and Progression (GARP) study.MethodsWe have measured eight biochemical markers, representing tissue turnover of cartilage, bone, synovium, and inflammation. ROA was assessed in the knees, hips, hands, vertebral facet joints and spinal disc degeneration (DD) by using the Kellgren score. A proportionate score was subsequently made for each joint location based on the number of joints with ROA. Principal component and linear mixed model analyses were applied to analyze the data.ResultsThree different clusters of markers were identified that may reflect different pathophysiological processes of OA. The first component appeared to be reflected by structural markers of cartilage and bone turnover and associated especially in subjects with hip ROA. The second component was reflected by a marker of inflammation and was associated with knee ROA, high Western Ontario and McMaster Universities (WOMAC) scores and body mass index (BMI). The third component included markers of cartilage turnover and was associated with ROA at hands, spine as well as age. High familial aggregation was observed for serum cartilage oligomeric matrix protein (S-COMP) (70%) and serum N-propeptide of collagen type IIA (S-PIIANP) (62%).ConclusionUsing a large well-characterized study and eight biochemical markers, we were able to observe three components that may reflect different molecular mechanisms (bone, cartilage, synovium turnover and inflammation). Our data suggested that these components contribute differently to ROA at different joint sites