Environmental factors in a population-based inception cohort of inflammatory bowel disease patients in Europe--an ECCO-EpiCom study.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageThe incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe possibly due to changes in environmental factors towards a more "westernised" standard of living. The aim of this study was to investigate differences in exposure to environmental factors prior to diagnosis in Eastern and Western European IBD patients.The EpiCom cohort is a population-based, prospective inception cohort of 1560 unselected IBD patients from 31 European countries covering a background population of 10.1 million. At the time of diagnosis patients were asked to complete an 87-item questionnaire concerning environmental factors.A total of 1182 patients (76%) answered the questionnaire, 444 (38%) had Crohn's disease (CD), 627 (53%) ulcerative colitis (UC), and 111 (9%) IBD unclassified. No geographic differences regarding smoking status, caffeine intake, use of oral contraceptives, or number of first-degree relatives with IBD were found. Sugar intake was higher in CD and UC patients from Eastern Europe than in Western Europe while fibre intake was lower (p<0.01). Daily consumption of fast food as well as appendectomy before the age of 20 was more frequent in Eastern European than in Western European UC patients (p<0.01). Eastern European CD and UC patients had received more vaccinations and experienced fewer childhood infections than Western European patients (p<0.01).In this European population-based inception cohort of unselected IBD patients, Eastern and Western European patients differed in environmental factors prior to diagnosis. Eastern European patients exhibited higher occurrences of suspected risk factors for IBD included in the Western lifestyle.Danish Colitis Crohn Patients Organisation (CCF) Vibeke Binder and Povl Riis Foundation Scientific Council at Herlev Hospital Sigrid Rignnor Moran Foundation, Aage and Johanne Louis-Hansens Foundation Munkholm Foundation C.C. Klestrup and Henriette Klestrup Foundation Knud and Dagny Gad Andresens Foundation Else and Mogens Wedell-Wedellsborgs Foundation Direktor Jacob Madsen and Olga Madsen's Foundation, Scan Ve

Yeast IME2 Functions Early in Meiosis Upstream of Cell Cycle-Regulated SBF and MBF Targets

BACKGROUND: In Saccharomyces cerevisiae, the G1 cyclin/cyclin-dependent kinase (CDK) complexes Cln1,-2,-3/Cdk1 promote S phase entry during the mitotic cell cycle but do not function during meiosis. It has been proposed that the meiosis-specific protein kinase Ime2, which is required for normal timing of pre-meiotic DNA replication, is equivalent to Cln1,-2/Cdk1. These two CDK complexes directly catalyze phosphorylation of the B-type cyclin/CDK inhibitor Sic1 during the cell cycle to enable its destruction. As a result, Clb5,-6/Cdk1 become activated and facilitate initiation of DNA replication. While Ime2 is required for Sic1 destruction during meiosis, evidence now suggests that Ime2 does not directly catalyze Sic1 phosphorylation to target it for destabilization as Cln1,-2/Cdk1 do during the cell cycle. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that Sic1 is eventually degraded in meiotic cells lacking the IME2 gene (ime2Δ), supporting an indirect role of Ime2 in Sic1 destruction. We further examined global RNA expression comparing wild type and ime2Δ cells. Analysis of these expression data has provided evidence that Ime2 is required early in meiosis for normal transcription of many genes that are also periodically expressed during late G1 of the cell cycle. CONCLUSIONS/SIGNIFICANCE: Our results place Ime2 at a position in the early meiotic pathway that lies upstream of the position occupied by Cln1,-2/Cdk1 in the analogous cell cycle pathway. Thus, Ime2 may functionally resemble Cln3/Cdk1 in promoting S phase entry, or it could play a role even further upstream in the corresponding meiotic cascade

Natural Disease Course of Ulcerative Colitis During the First Five Years of Follow-up in a European Population-based Inception Cohort-An Epi-IBD Study

International audienceBackground and Aims: Few population-based cohort studies have assessed the disease course of ulcerative colitis [UC] in the era of biological therapy and widespread use of immunomodulators. The aim of this study was to assess the 5-year outcome and disease course of patients with UC in the Epi-IBD cohort. Methods: In a prospective, population-based inception cohort of unselected patients with UC, patients were followed up from the time of their diagnosis, which included the collection of their clinical data, demographics, disease activity, medical therapy, and rates of surgery, cancers, and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis. Results: A total of 717 patients were included in the study. During follow-up, 43 [6%] patients underwent a colectomy and 163 [23%] patients were hospitalised. Of patients with limited colitis [distal to the left flexure], 90 [21%] progressed to extensive colitis. In addition, 92 [27%] patients with extensive colitis experienced a regression in disease extent, which was associated with a reduced risk of hospitalisation (hazard ratio [HR]: 0.5 95% CI: 0.3-0.8]. Overall, patients were treated similarly in both geographical regions; 80 [11%] patients needed biological therapy and 210 [29%] patients received immunomodulators. Treatment with immunomodulators was found to reduce the risk of hospitalisation [HR: 0.5 95% CI: 0.3-0.8]. Conclusions: Although patients in this population-based cohort were treated more aggressively with immunomodulators and biological therapy than in cohorts from the previous two decades, their disease outcomes, including colectomy rates, were no different. However, treatment with immunomodulators was found to reduce the risk of hospitalisation

Ancient origin of the biosynthesis of lignin precursors

BACKGROUND: Lignin plays an important role in plant structural support and water transport, and is considered one of the hallmarks of land plants. The recent discovery of lignin or its precursors in various algae has raised questions on the evolution of its biosynthetic pathway, which could be much more ancient than previously thought. To determine the taxonomic distribution of the lignin biosynthesis genes, we screened all publicly available genomes of algae and their closest non-photosynthetic relatives, as well as representative land plants. We also performed phylogenetic analysis of these genes to decipher the evolution and origin(s) of lignin biosynthesis. RESULTS: Enzymes involved in making p-coumaryl alcohol, the simplest lignin monomer, are found in a variety of photosynthetic eukaryotes, including diatoms, dinoflagellates, haptophytes, cryptophytes as well as green and red algae. Phylogenetic analysis of these enzymes suggests that they are ancient and spread to some secondarily photosynthetic lineages when they acquired red and/or green algal endosymbionts. In some cases, one or more of these enzymes was likely acquired through lateral gene transfer (LGT) from bacteria. CONCLUSIONS: Genes associated with p-coumaryl alcohol biosynthesis are likely to have evolved long before the transition of photosynthetic eukaryotes to land. The original function of this lignin precursor is therefore unlikely to have been related to water transport. We suggest that it participates in the biological defense of some unicellular and multicellular algae. REVIEWERS: This article was reviewed by Mark Ragan, Uri Gophna, Philippe Deschamps

Discriminatory ability of calcaneal quantitative ultrasound in the assessment of bone status in patients with inflammatory bowel disease

A high incidence of bone disease in patients with inflammatory bowel disease (IBD) requires frequent monitoring of skeletal status and, for that reason, evaluation of radiation-free technology is an issue of interest. Our objective was to appraise the parameters of calcaneal quantitative ultrasound (QUS): broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (QUI), and establish their t-score values to investigate discriminatory ability of QUS in IBD patients with metabolic bone disease. The study included 126 patients (Crohn's disease [n = 94] and ulcerative colitis [n = 32]), and 228 age- and sex-matched healthy volunteers. Bone status was evaluated on the same day by calcaneal QUS and dual-energy x-ray absorptiometry (DXA) at spine (L1-L4) and total hip. All QUS measurements were lower in patients compared with healthy controls (BUA p < 0.001; SOS p < 0.001; QUI p < 0.001) and correlated significantly but inversely with disease duration (r = -0.3, p = 0.002). There was no difference with respect to type of disease (Crohn's disease or ulcerative colitis) or corticosteroid therapy. All three QUS t-scores were significantly lower in patients who had previously sustained fragile fractures (n = 28) than in those without fracture in their history (n = 98) (t-scores: BUA -2.0 vs. -1.3, p = 0.008; SOS -2.1 vs. -1.4, p = 0.02: QUI -2.3 vs. -1.5, p = 0.009). Axial DXA was not significantly different between the fracture and nonfracture patients (-1.7 vs. -1.2, p = 0.1), whereas total hip DXA showed a discriminatory power between the two (-1.6 vs. -0.7, p = 0.001). Patients with t-score < -1.0 scanned by DXA were classified as bone disease. The sensitivity of QUS to identify bone disease was 93% and specificity 63%. The sensitivity of QUS to detect osteopenia was 84% and 72% for osteoporosis. Alternatively, lower negative QUS t-score cutoff </= -1.8 identified 83% of osteoporosis at lumbar spine and 100% at total hip. All three QUS variables had t-scores less than -1.8 when osteoporosis was detected at both spine and hip. However, the subgroup of IBD patients with QUI t-score cutoff </= -1.8 still included 26% of individuals with normal bone status. Calcaneal QUS measurements may identify patients with IBD who are at a higher risk of fracture independently of DXA measurements. However, QUS showed poor agreement with bone status scanned by DXA and a low discriminatory power between osteopenia and osteoporosis

Development of application ontology of Lenke's classification of scoliosis - OBR-Scolio

© 2015 IEEE. The objective of this paper is to demonstrate the creation process of the application ontology of scoliosis OBR-Scolio using the OBR reference ontology, which is spread over anatomy, physiology and pathology domains. Since OBR reference ontology exists only as a preliminary classification and does not possess taxonomy of pathological structure, we created the OBR-Scolio ontology by employing analogy with taxonomy of anatomical structure of the FMA reference ontology of anatomy. Also, we obtained the hierarchy of object and data properties of the OBR-Scolio ontology on the basic of FMA reference ontology. The OBR-Scolio ontology is employed in the web-based information system for visualization, monitoring and diagnosing of idiopathic scoliosis - ScolioMedIS. Considering that the key ontological concepts of the OBR-Scolio ontology are intended to define Lenke's classification of scoliosis, some of the main functionalities of this part of the information system ScolioMedIS include automation of process of determining Lenke's type of scoliosis and statistical demographic analysis of frequency of occurrence of each specific characteristic of scoliosis according to Lenke classification. In addition, this part of the system allows continuous monitoring of progression/regression of spinal curvatures for each registered patient with scoliosis, which could help in the process of management of medical treatment of scoliosis

Converting OBR-Scolio ontology in OWL DL

We developed the OBR-Scolio ontology that models scoliosis as pathological state of spine using the method of extracting from the FMA reference ontology in anatomical domain and the principal ontology framework of the OBR reference ontology, which is spread over anatomy, physiology and pathology domains. Following the FMA modeling framework, OBR-Scolio ontology initially is created in Protégé using its frame based representation. In order to enable more powerful reasoning support, ontology visualization, and more precise concepts' definition and description, we converted OBR-Scolio in OWL DL language, due to its higher expressiveness. The paper addresses and discusses the key conversion principles, as well as our experience in such conversion, and the results obtained from Racer reasoner

An ontology-based module of the information system ScolioMedIS for 3D digital diagnosis of adolescent scoliosis

© 2019 Elsevier B.V. Background and objective: Conventional information systems are built on top of a relational database. The main weakness of these systems is impossibility to define stable data schema ahead when the knowledge of the system is evolving and dynamic. The widely accepted alternatives to relational databases are ontologies that can be used for designing information systems. Many research papers describe various methods for improving reliability and precision in generating the type of the Lenke classification based on the image processing techniques or a computer program, but all of them require radiograph images. The main objective of this paper is to demonstrate the development of an ontology-based module of the information system ScolioMedIS for adolescent idiopathic scoliosis (AIS) diagnosis and monitoring, which uses optical 3D methods to determine the Lenke classification of AIS and to avoid harmful effects of traditional radiation diagnosis. Methods: For creating an ontology-based module of the ScolioMedIS we used the following steps: specification, conceptualization, formalization and implementation. In the specification and conceptualization phase we performed data collection and analysis to define domain, concepts and relationships for ontology design. In the formalization and implementation stage we developed the OBR-Scolio ontology and the ontology-based module of the ScolioMedIS. The module employs the Protégé-OWL API, as a collection of Java interfaces for the OBR-Scolio ontology, which enables the creating, deleting, and editing of the basic elements of the OBR-Scolio ontology, as well as the querying of the ontology. Results: The ontology-based module of ScolioMedIS is tested on the datasets of 20 female and 15 male patients with AIS between the ages of 11 and 18, to categorize spinal curvatures and to automatically generate statistical indicators about the frequency of the basic spinal curvatures, degree of progression or regression of deformity and statistical indicators about curvature characteristics according to the Lenke classification system and Lenke scoliosis types. Results are then compared with analysis of the Lenke classification of 315 observed patients, performed using traditional radiation techniques. Conclusions: This part of the system allows continuous monitoring of the progression/regression of spinal curvatures for each registered patient, which may provide a better management of scoliosis (diagnosis and treatment)

A discrete amino terminal domain of Kv1.5 and Kv1.4 potassium channels interacts with the spectrin repeats of α-actinin-2

AbstractThe interaction between the amino terminus of Kv1-type potassium channels and α-actinin-2 has been investigated. Using a combination of yeast two-hybrid analysis and in vitro binding assays, α-actinin-2 was found to bind to the N-termini of both Kv1.4 and Kv1.5 but not to the equivalent segments of Kv1.1, Kv1.2 or Kv1.3. Deletion analysis in the in vitro binding assays delineated the actinin binding region of Kv1.5 to between amino acids 73 and 148 of the channel. The Kv1.5 binding sites in α-actinin-2 were found to lie within actinin’s internal spectrin repeats. Unlike the reported interaction between actinin and the NMDA receptor, calmodulin was found to have no effect on actinin binding to Kv1.5

ScolioMedIS: Web-oriented information system for idiopathic scoliosis visualization and monitoring

Adolescent idiopathic scoliosis is the most common type of abnormal curvature observed in spine and it progresses rapidly during the puberty period. The most followed clinical way of assessing the spinal deformity is subjective by measuring the characteristic angles of spinal curve from a set of radiographic images. This paper presents a web-based information system (called ScolioMedIS) based on parameterized 3D anatomical models of the spine to quantitatively assess the deformity and to minimize the amount of radiation exposure by reducing the number of radiographs required. The main components of the system are 3D parametric solid model of spine, back surfaces, relevant clinical information and scoliosis ontology. The patient-specific spine model is regenerated from the parametric model and surface data using anatomical information extracted from radiographic images. The system is designed to take inherent advantage of Web for facilitating multi-center data collection and collaborative clinical decisions. The preliminary analysis of patient data showed promising results, which involve improved documentation standard, clinical decision knowledge base record, facilitated exchange and retrieval of medical data between institutions in multi-center clinical studies, 3D visualization of spinal deformity, and permanent monitoring of treatments. © 2012 Elsevier Ireland Ltd