Analyse protéomique des glioblastones: Quel est le meilleur contrôle?

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DNA methylation in glioblastoma: impact on gene expression and clinical outcome

International audienceBACKGROUND: Changes in promoter DNA methylation pattern of genes involved in key biological pathways have been reported in glioblastoma. Genome-wide assessments of DNA methylation levels are now required to decipher the epigenetic events involved in the aggressive phenotype of glioblastoma, and to guide new treatment strategies. RESULTS: We performed a whole-genome integrative analysis of methylation and gene expression profiles in 40 newly diagnosed glioblastoma patients. We also screened for associations between the level of methylation of CpG sites and overall survival in a cohort of 50 patients uniformly treated by surgery, radiotherapy and chemotherapy with concomitant and adjuvant temozolomide (STUPP protocol). The methylation analysis identified 616 CpG sites differentially methylated between glioblastoma and control brain, a quarter of which was differentially expressed in a concordant way. Thirteen of the genes with concordant CpG sites displayed an inverse correlation between promoter methylation and expression level in glioblastomas: B3GNT5, FABP7, ZNF217, BST2, OAS1, SLC13A5, GSTM5, ME1, UBXD3, TSPYL5, FAAH, C7orf13, and C3orf14. Survival analysis identified six CpG sites associated with overall survival. SOX10 promoter methylation status (two CpG sites) stratified patients similarly to MGMT status, but with a higher Area Under the Curve (0.78 vs. 0.71, p-value < 5e-04). The methylation status of the FNDC3B, TBX3, DGKI, and FSD1 promoters identified patients with MGMT-methylated tumors that did not respond to STUPP treatment (p-value < 1e-04). CONCLUSIONS: This study provides the first genome-wide integrative analysis of DNA methylation and gene expression profiles obtained from the same GBM cohort. We also present a methylome-based survival analysis for one of the largest uniformly treated GBM cohort ever studied, for more than 27,000 CpG sites. We have identified genes whose expression may be tightly regulated by epigenetic mechanisms and markers that may guide treatment decisions

NCBI GEO: archive for functional genomics data sets—10 years on

A decade ago, the Gene Expression Omnibus (GEO) database was established at the National Center for Biotechnology Information (NCBI). The original objective of GEO was to serve as a public repository for high-throughput gene expression data generated mostly by microarray technology. However, the research community quickly applied microarrays to non-gene-expression studies, including examination of genome copy number variation and genome-wide profiling of DNA-binding proteins. Because the GEO database was designed with a flexible structure, it was possible to quickly adapt the repository to store these data types. More recently, as the microarray community switches to next-generation sequencing technologies, GEO has again adapted to host these data sets. Today, GEO stores over 20 000 microarray- and sequence-based functional genomics studies, and continues to handle the majority of direct high-throughput data submissions from the research community. Multiple mechanisms are provided to help users effectively search, browse, download and visualize the data at the level of individual genes or entire studies. This paper describes recent database enhancements, including new search and data representation tools, as well as a brief review of how the community uses GEO data. GEO is freely accessible at http://www.ncbi.nlm.nih.gov/geo/

Conception of an anti-infectious and MRI visible mesh used for pelvic organs prolapse and abdominal hernias surgery

International audienceLa pose chirurgicale de prothèses afin de pallier les descentes d'organes de la zone pelvienne ou pariétale est une opération de plus en plus fréquente et requière l'implantation de plus de 1 200 000 dispositifs médicaux annuellement. Or, les cas de complications et de réinterventions chirurgicales restent très élevés, principalement dus aux infections associées à une réponse inflammatoire importante, ainsi qu'aux érosions, expositions et migrations des prothèses. Ces travaux présentent différentes stratégies permettant d'apporter des propriétés de résistance à l'infection et de suivi postopératoire à l'aide d'une visibilité en IRM à des treillis. Pour cela, un enrobage de polymères dégradables (polyesters) piégeant des antibiotiques est créé à l'aide d'un aérographe autour des filaments des treillis tout en conservant leurs aspects morphologiques et leurs propriétés mécaniques. Cet enrobage temporaire permet une libération prolongée de principes actifs inhibant l'adhésion bactérienne, la formation de biofilm et la prolifération bactérienne périprothétique pendant plus de trois jours in vitro. Parallèlement, des polymères contenant des agents de contraste greffés sur leur squelette carboné ont été utilisés comme agent d'enrobage, afin d'apporter des propriétés de visibilité en IRM aux treillis. In vitro, ces treillis enrobés induisent un signal significatif en IRM expérimentale (7 Tesla) et présentent une très bonne stabilité de l'agent de contraste, quelle que soit la technique de stérilisation employée. Surgical operations for soft tissue reinforcement (i.e. pelvic organs prolapse or abdominal hernias) are common procedures and require annually at least 1,200,000 of prostheses. Unfortunately, postoperatory complications and reinterventions are still important, mainly due to infection, inflammation, erosion, exposition or meshes migration. We present here several strategies to bring to meshes anti-infective resistance and clinical follow-up capability through an MRI visible material. A coating of the mesh by degradable polymers (polyesters) trapping antibiotics was created using an airbrushing technique, without modifying dramatically the morphology and the mechanical properties of the meshes. This temporary drug reservoir-coating allows a sustained release of the drugs and hamper in vitro bacterial contamination and biofilm formation on the meshes, associated to a large periprosthetic microorganism growth inhibition for a minimum of three days. Simultaneously, magnetic resonance contras

Prevalence, evaluation and management of overactive bladder in primary care

<p>Abstract</p> <p>Background</p> <p>Patients with overactive bladder (OAB) are under-diagnosed in the primary care setting. Primary care physicians (PCP) approach to the patient and appropriate patient disclosure may contribute to under-diagnosis.</p> <p>Methods</p> <p>An outpatient primary care setting was used to determine the prevalence and characteristics of OAB. Patients who visited the family medicine outpatient clinic were invited to answer a self-administered questionnaire. It included questions on evidence of lower urinary tract symptoms (modified Overactive Bladder-Validated 8-question Screener [OAB-V8]), relevant medical and surgical history, and demographic data. Relationship between OAB and other independent variables were analyzed using chi-square and risk ratio (RR) analysis.</p> <p>Results</p> <p>Of 325 questionnaires distributed, 311 were returned completed. Patients ranged from 18 to 97 years, the majority women (74.0%) and African American (74.3%). OAB was present in 60.5% of men and 48.3% of women (<it>p </it>= 0.058). OAB was significantly associated with obesity (BMI > = 30) in women (<it>p </it>= 0.018, RR = 1.72), specifically obese premenopausal women (age < 55 years) (<it>p </it>= 0.011, RR = 1.98).</p> <p>Conclusion</p> <p>OAB prevalence is more than double and higher in men than previously reported. The relative risk for OAB is significantly greater in obese premenopausal women.</p

A structured overview of simultaneous component based data integration

<p>Abstract</p> <p>Background</p> <p>Data integration is currently one of the main challenges in the biomedical sciences. Often different pieces of information are gathered on the same set of entities (e.g., tissues, culture samples, biomolecules) with the different pieces stemming, for example, from different measurement techniques. This implies that more and more data appear that consist of two or more data arrays that have a shared mode. An integrative analysis of such coupled data should be based on a simultaneous analysis of all data arrays. In this respect, the family of simultaneous component methods (e.g., SUM-PCA, unrestricted PCovR, MFA, STATIS, and SCA-P) is a natural choice. Yet, different simultaneous component methods may lead to quite different results.</p> <p>Results</p> <p>We offer a structured overview of simultaneous component methods that frames them in a principal components setting such that both the common core of the methods and the specific elements with regard to which they differ are highlighted. An overview of principles is given that may guide the data analyst in choosing an appropriate simultaneous component method. Several theoretical and practical issues are illustrated with an empirical example on metabolomics data for <it>Escherichia coli </it>as obtained with different analytical chemical measurement methods.</p> <p>Conclusion</p> <p>Of the aspects in which the simultaneous component methods differ, pre-processing and weighting are consequential. Especially, the type of weighting of the different matrices is essential for simultaneous component analysis. These types are shown to be linked to different specifications of the idea of a fair integration of the different coupled arrays.</p

Trocar-guided total tension-free vaginal mesh repair of post-hysterectomy vaginal vault prolapse

Contains fulltext : 81076.pdf (publisher's version ) (Closed access)INTRODUCTION AND HYPOTHESIS: The objective of this study was to report 1 year anatomical and functional outcomes of trocar-guided total tension-free vaginal mesh (Prolift) repair for post-hysterectomy vaginal vault prolapse with one continuous piece of polypropylene mesh. METHODS: We conducted a prospective observational cohort study of 46 patients. A minimum sample size of 35 patients was needed to detect a recurrence rate of less than 20% at 12 months. Instruments of measurement used were pelvic organ prolapse quantification and validated questionnaires. RESULTS: Overall anatomical success was 91% (95% confidence interval 83-99), with significant improvement in experienced bother and quality of life. Mesh exposure occurred in seven patients (15%). No adverse effects on sexual function could be detected. CONCLUSIONS: Trocar-guided total tension-free vaginal mesh (Prolift) repair with one continuous piece of mesh for post-hysterectomy vaginal vault prolapse is well tolerated and anatomically and functionally highly effective. Results of controlled trials will determine its position in the operative armamentarium

Prevalence and risk factors for mesh erosion after laparoscopic-assisted sacrocolpopexy

The purpose of this study is to identify risk factors for mesh erosion in women undergoing minimally invasive sacrocolpopexy (MISC). We hypothesize that erosion is higher in subjects undergoing concomitant hysterectomy. This is a retrospective cohort study of women who underwent MISC between November 2004 and January 2009. Demographics, operative techniques, and outcomes were abstracted from medical records. Multivariable regression identified odds of erosion. Of 188 MISC procedures 19(10%) had erosions. Erosion was higher in those with total vaginal hysterectomy (TVH) compared to both post-hysterectomy (23% vs. 5%, p = 0.003) and supracervical hysterectomy (SCH) (23% vs. 5%, p = 0.109) groups. In multivariable regression, the odds of erosion for TVH was 5.67 (95% CI: 1.88–17.10) compared to post-hysterectomy. Smoking, the use of collagen-coated mesh, transvaginal dissection, and mesh attachment transvaginally were no longer significant in the multivariable regression model. Based on this study, surgeons should consider supracervical hysterectomy over total vaginal hysterectomy as the procedure of choice in association with MISC unless removal of the cervix is otherwise indicated

A Spaetzle-like role for nerve growth factor beta in vertebrate immunity to Staphylococcus aureus

Many key components of innate immunity to infection are shared between Drosophila and humans. However, the fly Toll ligand Spaetzle is not thought to have a vertebrate equivalent. We have found that the structurally related cystine-knot protein, nerve growth factor β (NGFβ), plays an unexpected Spaetzle-like role in immunity to Staphylococcus aureus infection in chordates. Deleterious mutations of either human NGFβ or its high-affinity receptor tropomyosin-related kinase receptor A (TRKA) were associated with severe S. aureus infections. NGFβ was released by macrophages in response to S. aureus exoproteins through activation of the NOD-like receptors NLRP3 and NLRC4 and enhanced phagocytosis and superoxide-dependent killing, stimulated proinflammatory cytokine production, and promoted calcium-dependent neutrophil recruitment. TrkA knockdown in zebrafish increased susceptibility to S. aureus infection, confirming an evolutionarily conserved role for NGFβ-TRKA signaling in pathogen-specific host immunity