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1. Guidelines for mouse and human DC generation

Author

Manfred B. Lutz, Shafaqat Ali, Cindy Audiger, Stella E. Autenrieth, Luciana Berod, Venetia Bigley, Laura Cyran, Marc Dalod, Jan Dörrie, Diana Dudziak, Georgina Flórez‐Grau, Lucila Giusiano, Gloria J. Godoy, Marion Heuer, Anne B. Krug, Christian H. K. Lehmann, Christian T. Mayer, Shalin H. Naik, Stefanie Scheu, Gerty Schreibelt, Elodie Segura, Kristin Seré, Tim Sparwasser, Jurjen Tel, Huaming Xu, Martin Zenke, University of Würzburg, Institute of Medical Microbiology and Hospital Hygiene (University of Düsseldorf), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], The Walter and Eliza Hall Institute of Medical Research (WEHI), University of Melbourne, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University of Tübingen, University Medical Center of the Johannes Gutenberg-University Mainz, Newcastle University [Newcastle], Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universitätsklinikum Erlangen [Erlangen], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), University Hospital Erlangen = Uniklinikum Erlangen, Radboud Institute for Molecular Life Sciences [Nijmegen, the Netherlands], Ludwig Maximilian University [Munich] (LMU), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL), Universitätsklinikum RWTH Aachen - University Hospital Aachen [Aachen, Germany] (UKA), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Eindhoven University of Technology [Eindhoven] (TU/e), University of Duisburg-Essen, and Dalod, Marc

Subjects
In vitro, Immunology, Generation, Immunology and Allergy, endritic cells, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Isolation
Abstract

European journal of immunology (2022). doi:10.1002/eji.202249816, Published by Wiley-VCH, Weinheim

Published
2022

2. Viscoelastic properties of suspended cells measured with shear flow deformation cytometry

Author

Richard Gerum, Elham Mirzahossein, Mar Eroles, Jennifer Elsterer, Astrid Mainka, Andreas Bauer, Selina Sonntag, Alexander Winterl, Johannes Bartl, Lena Fischer, Shada Abuhattum, Ruchi Goswami, Salvatore Girardo, Jochen Guck, Stefan Schrüfer, Nadine Ströhlein, Mojtaba Nosratlo, Harald Herrmann, Dorothea Schultheis, Felix Rico, Sebastian Müller, Stephan Gekle, Ben Fabry, Biophysics Group Friedrich-Alexander University, Van der Waals-Zeeman Institute, University of Amsterdam [Amsterdam] (UvA), Adhésion et Inflammation (LAI), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Max Planck Institute for the Science of Light, Max-Planck-Gesellschaft, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Universitätsklinikum Erlangen [Erlangen], University Hospital Erlangen = Uniklinikum Erlangen, Deutsche Forschungsgemeinschaft TRR-SFB 225 subprojects A01 Elham MirzahosseinHorizon 2020 No 812772 Mar ErolesHorizon 2020 No 953121 Mar Eroles Deutsche Forschungsgemeinschaft B07 Stephan GekleDeutsche Forschungsgemeinschaft A07 Stefan Schruefer, European Project: 812772,Phys2BioMed, and European Project: 953121

Subjects
General Immunology and Microbiology, Viscosity, [SDV]Life Sciences [q-bio], ddc:570, General Neuroscience, Stress, Mechanical, General Medicine, Flow Cytometry, Rheology, Elasticity, General Biochemistry, Genetics and Molecular Biology
Abstract

Numerous cell functions are accompanied by phenotypic changes in viscoelastic properties, and measuring them can help elucidate higher level cellular functions in health and disease. We present a high-throughput, simple and low-cost microfluidic method for quantitatively measuring the elastic (storage) and viscous (loss) modulus of individual cells. Cells are suspended in a high-viscosity fluid and are pumped with high pressure through a 5.8 cm long and 200 µm wide microfluidic channel. The fluid shear stress induces large, ear ellipsoidal cell deformations. In addition, the flow profile in the channel causes the cells to rotate in a tank-treading manner. From the cell deformation and tank treading frequency, we extract the frequency-dependent viscoelastic cell properties based on a theoretical framework developed by R. Roscoe [1] that describes the deformation of a viscoelastic sphere in a viscous fluid under steady laminar flow. We confirm the accuracy of the method using atomic force microscopy-calibrated polyacrylamide beads and cells. Our measurements demonstrate that suspended cells exhibit power-law, soft glassy rheological behavior that is cell-cycle-dependent and mediated by the physical interplay between the actin filament and intermediate filament networks.Cells in the human body are viscoelastic: they have some of the properties of an elastic solid, like rubber, as well as properties of a viscous fluid, like oil. To carry out mechanical tasks – such as, migrating through tissues to heal a wound or to fight inflammation – cells need the right balance of viscosity and elasticity. Measuring these two properties can therefore help researchers to understand important cell tasks and how they are impacted by disease. However, quantifying these viscous and elastic properties is tricky, as both depend on the time-scale they are measured: when pressed slowly, cells appear soft and liquid, but they turn hard and thick when rapidly pressed. Here, Gerum et al. have developed a new system for measuring the viscosity and elasticity of individual cells that is fast, simple, and inexpensive. In this new method, cells are suspended in a specialized solution with a consistency similar to machine oil which is then pushed with high pressure through channels less than half a millimeter wide. The resulting flow of fluid shears the cells, causing them to elongate and rotate, which is captured using a fast camera that takes 500 images per second. Gerum et al. then used artificial intelligence to extract each cell’s shape and rotation speed from these images, and calculated their viscosity and elasticity based on existing theories of how viscoelastic objects behave in fluids. Gerum et al. also investigated how the elasticity and viscosity of cells changed with higher rotation frequencies, which corresponds to shorter time-scales. This revealed that while higher frequencies made the cells appear more viscous and elastic, the ratio between these two properties remained the same. This means that researchers can compare results obtained from different experimental techniques, even if the measurements were carried out at completely different frequencies or time-scales. The method developed by Gerum et al. provides a fast an inexpensive way for analyzing the viscosity and elasticity of cells. It could also be a useful tool for screening the effects of drugs, or as a diagnostic tool to detect diseases that affect the mechanical properties of cells.

Published
2022

3. SCCS OPINION on Acid Yellow 3 – C054 (CAS No. 8004-92-0, EC. No 305-897-5) - Submission II - SCCS/1631/21 – Final Opinion

Author

Bernauer, Ulrike, Bodin, Laurent, Chaudhry, Qasim, Coenraads, Pieter J., Dusinska, Maria, Ezendam, Janine, Gaffet, Eric, Galli, Corrado Lodovico, Granum, Berit Brunstad, Panteri, Eirini, Rogiers, Vera, Rousselle, Christophe, Stepnik, Maciej, Vanhaecke, Tamara, Wijnhoven, Susan, Koutsodimou, Aglaia, Uter, Wolfgang, von Götz, Natalie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Scientific Committee for Consumer Safety (SCCS) (SCCS), Institut Jean Lamour (IJL), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Scientific Committee for Consumer Safety (SCCS), Publications Office of the European Union, German Federal Institute for Risk Assessment [Berlin] (BfR), CEA- Saclay (CEA), University of Chester, University Medical Center Groningen [Groningen] (UMCG), Norwegian Institute for Air Research (NILU), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Università degli Studi di Milano = University of Milan (UNIMI), Norwegian Institute of Public Health [Oslo] (NIPH), National and Kapodistrian University of Athens (NKUA), Vrije Universiteit Brussel (VUB), Direction des affaires européennes et internationales (DAEI), QSAR lab, General Chemical State Laboratory (GCSL), University Hospital Erlangen = Uniklinikum Erlangen, Swiss Federal Office of Public Health, Scientific Committee for Consumer Safety (European Commission), Université de Lorraine (UL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Milan, University-Hospital Erlangen, University of Erlangen-Nuremberg - Universität tsstr. 21-23, 91054 Erlangen DE, and Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)

Subjects
Acid Yellow 3, hair dye, SCCS, CAS Number 8004-92-0, Regulation 1223/2009, EC No 305-897-5, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], scientific opinion
Abstract

International audience; SCCS OPINION on Acid Yellow 3 – C054 (CAS No. 8004-92-0, EC. No 305-897-5) - Submission II - SCCS/1631/21 – Final OpinionU. Bernauer, L. Bodin, Q. Chaudhry, P.J. Coenraads, M. Dusinska, J. Ezendam, E. Gaffet, C. L. Galli, B. Granum, E. Panteri, V. Rogiers, Ch. Rousselle, M. Stepnik, T. Vanhaecke, S. Wijnhoven, A. Koutsodimou, W. Uter, N. von GoetzThe SCCS adopted this document by written procedure on 23 July 2021 (31 Pages)Mise en ligne le 26 Juillet 2021 https://ec.europa.eu/health/sites/default/files/scientific_committees/consumer_safety/docs/sccs_o_253.pdfConclusion of the opinion: (1) In light of the data provided, does the SCCS consider Acid Yellow 3, safe when used in non-oxidative hair colouring products up to a maximum on-head concentration of 0.5 %?Based on the data provided in the dossier, the SCCS considers that Acid Yellow 3 is safe when used in non-oxidative hair colouring products at on-head concentrations of up to 0.5%.(2) Does the SCCS have any further scientific concerns with regard to the use of Acid Yellow 3 in cosmetic products?A detailed analytical report on the test substance in representative batches and results of the stability tests should be provided to exclude the possibility of the presence of any impurities that may be of concern.Keywords:SCCS, scientific opinion, Acid Yellow 3, hair dye, Regulation 1223/2009, CAS Number 8004-92-0, EC No 305-897-5Opinion to be cited as:SCCS (Scientific Committee on Consumer Safety), Opinion on Acid Yellow 3 – C054 (CAS Number 8004-92-0, EC No 305-897-5), submission II, preliminary version of 7 May 2021, final version of 23 July 2021, SCCS/1631/21.

Published
2022

4. Biology of BCG response in non-muscle invasive bladder cancer - 2021 IBCN Updates Part III

Author

M.J. Reike, M.A. Ingersoll, D.C. Müller, T.C.M. Zuiverloon, T. Strandgaard, A.M. Kamat, S.B. Williams, R. Seiler, T. Todenhöfer, L. Dyrskjøt, R. Nawroth, P. Goebell, B. Schmitz-Dräger, J.P. Sfakianos, J. Meeks, A. Horowitz, P.C. Black, University of British Columbia [Vancouver], Inflammation et immunité des muqueuses - Mucosal Inflammation and Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of Basel (Unibas), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Aarhus University Hospital, Aarhus University [Aarhus], The University of Texas Medical School at Houston, The University of Texas Medical Branch (UTMB), Technische Universität München = Technical University of Munich (TUM), University Hospital Erlangen = Uniklinikum Erlangen, Icahn School of Medicine at Mount Sinai [New York] (MSSM), and Northwestern University Feinberg School of Medicine

Subjects
MESH: Humans, Bacillus Calmette-Guerin (BCG), MESH: Immunotherapy, Urology, [SDV]Life Sciences [q-bio], Bladder cancer, MESH: Non-Muscle Invasive Bladder Neoplasms, MESH: Adjuvants, Immunologic, MESH: Neoplasm Invasiveness, MESH: Urinary Bladder Neoplasms, MESH: BCG Vaccine, SDG 3 - Good Health and Well-being, Oncology, MESH: Biology, Immunotherapy, MESH: Neoplasm Recurrence, Local, MESH: Administration, Intravesical
Abstract

International audience; Bacillus Calmette-Guerin (BCG) remains the only FDA-approved first-line therapy in patients with high-risk non-muscle invasive bladder cancer. Recurrences, even after adequate BCG therapy, are common and the efficacy of second-line therapies remains modest. Therefore, early identification of patients likely to recur and treatment after recurrence remain critical unmet needs in the clinical care of bladder cancer patients. To address these deficits, a better understanding of the mechanisms of resistance to BCG-therapy is needed. The virtual update of the International Bladder Cancer Network (IBCN) on the biology of response to BCG focused on potential mechanisms and markers of resistance to intravesical BCG therapy. The insights from this meeting will be highlighted and put into context of previously reported mechanisms of resistance to BCG in this review.

Published
2022

5. NT-proBNP and stem cell factor plasma concentrations are independently associated with cardiovascular outcomes in end-stage renal disease hemodialysis patients

Author

P Rossignol, K Duarte, E Bresso, Åsberg A, M D Devignes, N Eriksson, N Girerd, R Glerup, A G Jardine, H Holdaas, Z Lamiral, C Leroy, Z Massy, W März, B Krämer, P H Wu, R Schmieder, I Soveri, J H Christensen, M Svensson, F Zannad, B Fellström, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Hôpital Princesse Grace [Monaco], Computational Algorithms for Protein Structures and Interactions (CAPSID), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Complex Systems, Artificial Intelligence & Robotics (LORIA - AIS), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Department of Transplantation Medicine Oslo University Hospital-Rikshospitalet, University of Oslo (UiO), UCR Uppsala Clinical Research Center, Uppsala Science Park, Department of Nephrology, Aalborg University Hospital, British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), University of Glasgow-NHS Greater Glasgow and Clyde, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service Néphrologie/Dialyse [AP-HP Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], University Hospital Mannheim | Universitätsmedizin Mannheim, Medical University of Graz, Uppsala Universitet [Uppsala], Kaohsiung Medical University Hospital [Kaohsiung, Taïwan], Kaohsiung Medical University [Kaohsiung, Taïwan] (KMU), University Hospital Erlangen = Uniklinikum Erlangen, Aarhus University Hospital, The original AURORA trial was sponsored by Astra ZENECA. The present analyses and statistical work presented in this paper were jointly sponsored by the involved universities (R.S., A.J., H.H., B.F., W.M., and B.K.K.), ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), and ANR-15-IDEX-0004,LUE,Isite LUE(2015)

Subjects
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, NT-proBNP, Urologi och njurmedicin, Urology and Nephrology, Cardiovascular, Prognosis, Chronic hemodialysis, Cardiovascula, Stem cell factor
Abstract

AimsEnd-stage renal disease (ESRD) treated by chronic hemodialysis (HD) is associated with poor cardiovascular (CV) outcomes, with no available evidence-based therapeutics. A multiplexed proteomic approach may identify new pathophysiological pathways associated with CV outcomes, potentially actionable for precision medicine.Methods and resultsThe AURORA trial was an international, multicentre, randomized, double-blind trial involving 2776 patients undergoing maintenance HD. Rosuvastatin vs. placebo had no significant effect on the composite primary endpoint of death from CV causes, nonfatal myocardial infarction or nonfatal stroke. We first compared CV risk-matched cases and controls (n = 410) to identify novel biomarkers using a multiplex proximity extension immunoassay (276 proteomic biomarkers assessed with OlinkTM). We replicated our findings in 200 unmatched cases and 200 controls. External validation was conducted from a multicentre real-life Danish cohort [Aarhus-Aalborg (AA), n = 331 patients] in which 92 OlinkTM biomarkers were assessed. In AURORA, only N-terminal pro-brain natriuretic peptide (NT-proBNP, positive association) and stem cell factor (SCF) (negative association) were found consistently associated with the trial's primary outcome across exploration and replication phases, independently from the baseline characteristics. Stem cell factor displayed a lower added predictive ability compared with NT-ProBNP. In the AA cohort, in multivariable analyses, BNP was found significantly associated with major CV events, while higher SCF was associated with less frequent CV deaths.ConclusionsOur findings suggest that NT-proBNP and SCF may help identify ESRD patients with respectively high and low CV risk, beyond classical clinical predictors and also point at novel pathways for prevention and treatment.

Published
2022

6. Reproducibility of mRNA-Based Testing of ESR1, PGR, ERBB2, and MKI67 Expression in Invasive Breast Cancer—A Europe-Wide External Quality Assessment

Author

Thomas Mairinger, Giuseppe Viale, Tamara Caniego Casas, Paul Jank, Frédérique Penault-Llorca, Iris M. Simon, Fulvia Ferrazzi, Peter A. Fasching, Robert Stöhr, Jodi Weidler, Elena Guerini Rocco, Anne Cayre, Belén Pérez-Mies, Hanna Huebner, Ramona Erber, Carsten Denkert, José Palacios, Miriam Zentgraf, Lina Khoury, Arndt Hartmann, Verena Popp, Josephine Fischer, Steffi Becker, Matthias W. Beckmann, Matthias Ruebner, University Hospital Erlangen [Germany], European Institute of Oncology [Milan] (ESMO), University of Milan, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Instituto Ramon y Cajal de Investigacion Sanitaria [Madrid, Spain] (IRYCIS), Universidad de Alcalá - University of Alcalá (UAH), Instituto de Salud Carlos III [Madrid] (ISC), Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá de Henares (UAH), Philipps University of Marburg, Helios Hospital, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), University Hospital Erlangen = Uniklinikum Erlangen, Università degli Studi di Milano = University of Milan (UNIMI), and Philipps Universität Marburg = Philipps University of Marburg

Subjects
Oncology, Cancer Research, medicine.medical_specialty, MKI67, [SDV]Life Sciences [q-bio], STRAT4, Estrogen receptor, GeneXpert, In situ hybridization, 03 medical and health sciences, breast cancer, 0302 clinical medicine, Breast cancer, Internal medicine, Progesterone receptor, External quality assessment, medicine, ddc:610, Xpert, skin and connective tissue diseases, PGR, RC254-282, 030304 developmental biology, 0303 health sciences, business.industry, mRNA expression testing, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, ESR1, Gold standard (test), medicine.disease, 3. Good health, ERBB2, 030220 oncology & carcinogenesis, Immunohistochemistry, business, Estrogen receptor alpha
Abstract

Estrogen receptor (ER), progesterone receptor (PgR), Ki-67, and HER2 immunohistochemistry (IHC) together with HER2 in situ hybridization (ISH) are utilized to classify invasive breast cancer (IBC) into predictive molecular subtypes. As IHC evaluation may be hampered by analytical errors, gene expression assays could offer a reliable alternative. In this first Europe-wide external quality assessment (EQA) study, we investigated performance of mRNA-based Xpert® Breast Cancer STRAT4 (CE-IVD) in five European laboratories. The cohort comprised ten pre-therapy IBC core biopsies diagnosed in the coordinating center (CC). STRAT4 binary (positive or negative) mRNA results of each marker (ESR1, PGR, ERBB2,&nbsp, MKI67) were compared with the gold standard IHC/ISH performed by the CC. Sensitivity, specificity, and accuracy of ESR1 and ERBB2 mRNA were 100% for all samples. In contrast, PGR expression was falsely negative for one case by two sites and MKI67 falsely negative for two cases (respectively by four and one sites). These cases had STRAT4 expression values close to assay cut-offs and immunohistochemically presented heterogeneous low positive PgR and heterogeneous Ki-67. Our EQA shows that STRAT4 mRNA assay may be a reproducible method to evaluate ER, PgR, HER2, and Ki-67 status. However, cases with expression values close to assay cut-offs should be carefully reviewed.

Published
2021

7. Opinion on Methyl salicylate (methyl 2-hydroxybenzoate) - Submission I - SCCS/1633/21- Preliminary Opinion

Author

Bernauer, Ulrike, Bodin, Laurent, Chaudhry, Qasim, Coenraad, Pieter J., Dusinska, Maria, Ezendam, Janine, Gaffet, Eric, Galli, Corrado Lodovico, Granum, Berit Brunstad, Panteri, Eirini, Rogiers, Vera, Rousselle, Christophe, Stepnik, Maciej, Vanhaecke, Tamara, Wijnhoven, Susan, Koutsodimou, Aglaia, Uter, Wolfgang, von Goetz, Natalie, German Federal Institute for Risk Assessment [Berlin] (BfR), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Scientific Committee for Consumer Safety (SCCS) (SCCS), University of Chester, University Medical Center Groningen [Groningen] (UMCG), Norwegian Institute for Air Research (NILU), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Institut Jean Lamour (IJL), Université de Lorraine (UL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Milan, Norwegian Institute of Public Health [Oslo] (NIPH), National and Kapodistrian University of Athens (NKUA), Vrije Universiteit Brussel (VUB), Direction des affaires européennes et internationales (DAEI), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), QSAR lab, General Chemical State Laboratory (GCSL), University-Hospital Erlangen, University of Erlangen-Nuremberg - Universität tsstr. 21-23, 91054 Erlangen DE, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Swiss Federal Office of Public Health, Scientific Committee for Consumer Safety (European Commission), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano = University of Milan (UNIMI), and University Hospital Erlangen = Uniklinikum Erlangen

Subjects
Methyl 2-hydroxybenzoate, SCCS, Regulation 1223/2009, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], Scientific opinion, Methyl salicylate
Abstract

International audience; SCCS OPINION on Methyl salicylate (methyl 2-hydroxybenzoate) - Submission I - SCCS/1633/21- Preliminary OpinionU. Bernauer, L. Bodin, Q. Chaudhry, P.J. Coenraad, M. Dusinska, J. Ezendam, E. Gaffet, C. L. Galli, B. Granum, E. Panteri, V. Rogiers, Ch. Rousselle, M. Stepnik, T. Vanhaecke, S. Wijnhoven, A. Koutsodimou, W. Uter, N. von GoetzThe SCCS adopted this document at its plenary meeting on 24-25 June 2021 ( (80 pages)Mise en ligne le 9 Juillet 2021https://ec.europa.eu/health/sites/default/files/scientific_committees/consumer_safety/docs/sccs_o_255.pdfConclusion of the opinion: (1) In light of the data provided and taking under consideration the RAC Opinion on Methyl salicylate and the expected new classification as Toxic for Reproduction Category 2 of Methyl salicylate (to be introduced by an update of Annex VI Reg. 1272/2008), does the SCCS consider Methyl salicylate safe when used up to the maximum concentrations provided in the dossier submitted by the applicant?The SCCS considers Methyl salicylate safe when used in cosmetic products up to the maximum concentrations provided in the dossier submitted by the applicant as detailed in Table 1, except for mouth washes used below 10 years old.(2) Does the SCCS have any further scientific concerns with regard to the use of Methyl salicylate in cosmetic products, also in relation to the RAC recommended classification of Methyl salicylate as ‘Skin sensitizer Category 1B’?Methyl salicylate should be considered as a weak skin sensitiser in humans and eye irritant.Moreover the SCCS would like also to express other concerns related to the use of methyl salicylate:- Methyl salicylate can be used in consumer products other than cosmetic products, such as household cleaning products, air care products, biocides (e.g. disinfectants, pest control products), polishes and waxes which may increase the systemic exposure dose with a possibility to exceed the safe level.- Methyl salicylate will be metabolised in the body to salicylic acid which is also classified as a reprotoxicant and used in cosmetic products (see opinion SCCS/1601/18). Therefore the combined exposure to cosmetic products containing various salicylates may increase the systemic exposure dose with a possibility to exceed the safe level.The SCCS also notices that wintergreen oil that is used in cosmetic products may contain up to 99% methyl salicylate. Therefore when calculating the content of methyl salicylate in a cosmetic product, any fraction coming from wintergreen oil should also be considered.Keywords:SCCS, scientific opinion, methyl salicylate, methyl 2-hydroxybenzoate, Regulation 1223/2009Opinion to be cited as:SCCS (Scientific Committee on Consumer Safety), Opinion on methyl salicylate (methyl 2-hydroxybenzoate), preliminary version of 24-25 June, SCCS/1633/21.

Published
2021

8. Opinion of the Scientific Committee on Consumer safety (SCCS) – Final Opinion on propylparaben (CAS No 94-13-3, EC No 202-307-7)

Author

Eric Gaffet, Ulrike Bernauer, Corrado Ludovico Galli, Natalie von Goetz, Tamara Vanhaecke, Pieter J. Coenraads, Maciej Stępnik, Wolfgang Uter, Janine Ezendam, Eirini Panteri, Laurent Bodin, A. Koutsodimou, Christophe Rousselle, Susan Wijnhoven, Vera Rogiers, Berit Granum, Qasim Chaudhry, Maria Dusinska, CEA- Saclay (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Scientific Committee for Consumer Safety (SCCS) (SCCS), Vrije Universiteit Brussel (VUB), German Federal Institute for Risk Assessment [Berlin] (BfR), University of Chester, University Medical Center Groningen [Groningen] (UMCG), Norwegian Institute for Air Research (NILU), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Institut Jean Lamour (IJL), Université de Lorraine (UL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Milan, Norwegian Institute of Public Health [Oslo] (NIPH), National and Kapodistrian University of Athens (NKUA), Direction des affaires européennes et internationales (DAEI), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), QSAR lab, General Chemical State Laboratory (GCSL), University-Hospital Erlangen, University of Erlangen-Nuremberg - Universität tsstr. 21-23, 91054 Erlangen DE, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Swiss Federal Office of Public Health, Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano = University of Milan (UNIMI), University Hospital Erlangen = Uniklinikum Erlangen, Pharmaceutical and Pharmacological Sciences, and Experimental in vitro toxicology and dermato-cosmetology

Subjects
Preservative, Parabens, 010501 environmental sciences, Toxicology, 01 natural sciences, Consumer safety, Propylparaben, EC No 202-307-7, 03 medical and health sciences, chemistry.chemical_compound, Human health, SCCS/1623/20, Medicine, Humans, Scientific opinion, CAS No 94-13-3, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0105 earth and related environmental sciences, 0303 health sciences, Dose-Response Relationship, Drug, business.industry, Regulation 1223/2009, Preservatives, Pharmaceutical, Subject (documents), General Medicine, 3. Good health, SCCS, chemistry, 13. Climate action, Consumer Product Safety, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], Endocrine effects, Point of departure, business
Abstract

In cosmetic products, the ingredient propylparaben (CAS No 94-13-3, EC No 202-307-7) with the chemical names Propyl 4-hydroxybenzoate and 4-Hydroxybenzoic acid propyl ester is currently regulated as a preservative in a concentration up to 0.14% (as acid) (Annex V/12a). In addition, a safe concentration was established for mixtures of parabens, where the sum of the individual concentrations should not exceed 0.8% (as acid). However, in such mixtures the sum of the individual concentrations of butyl- and propylparaben and their salts should not exceed 0.14%. Propylparaben was subject to different safety evaluations in 2005 (SCCP/0874/05), 2006 (SCCP/1017/06), 2008 (SCCP/1183/08), 2010 (SCCS/1348/10), 2011 (SCCS/1446/11), and in 2013 (SCCS/1514/13). On the basis of the safety assessment of propylparaben, and considering the concerns related to potential endocrine disrupting properties, the SCCS has concluded that propylparaben is safe when used as a preservative in cosmetic products up to a maximum concentration of 0.14%. The available data on propylparaben provide some indications for potential endocrine effects. However, the current level of evidence is not sufficient to regard it as an endocrine disrupting substance, or to derive a toxicological point of departure based on endocrine disrupting properties for use in human health risk assessment. The SCCS mandate does not address environmental aspects. Therefore, this assessment did not cover the safety of propylparaben for the environment. Link to the Opinion (SCCS/1623/20): https://ec.europa.eu/health/sites/default/files/scientific_committees/consumer_safety/docs/sccs_o_243.pdf

Published
2021

9. SCCS Opinion on Homosalate - SCCS/1622/20 - Final Opinion

Author

Bernauer, U., Bodin, L., Chaudhry, Q., Coenraads, P.J., Dusinska, M., Ezendam, J., Gaffet, E., Galli, C. L., Granum, B., Panteri, E., Rogiers, V., Rousselle, Ch., Stepnik, M., Vanhaecke, T., Wijnhoven, S., Koutsodimou, A., Uter, W., Goetz, N. Von, German Federal Institute for Risk Assessment [Berlin] (BfR), CEA- Saclay (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Scientific Committee for Consumer Safety (SCCS) (SCCS), University of Chester, University Medical Center Groningen [Groningen] (UMCG), Norwegian Institute for Air Research (NILU), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Institut Jean Lamour (IJL), Université de Lorraine (UL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Milan, Norwegian Institute of Public Health [Oslo] (NIPH), National and Kapodistrian University of Athens (NKUA), Vrije Universiteit Brussel (VUB), Direction des affaires européennes et internationales (DAEI), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), QSAR lab, General Chemical State Laboratory (GCSL), University-Hospital Erlangen, University of Erlangen-Nuremberg - Universität tsstr. 21-23, 91054 Erlangen DE, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Swiss Federal Office of Public Health, Scientific Committee for Consumer Safety (European Commission), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano = University of Milan (UNIMI), University Hospital Erlangen = Uniklinikum Erlangen, Scientific Committee for Consumer Safety (SCCS), and Publications Office of the European Union

Subjects
SCCS, CAS No 118-56-9, Regulation 1223/2009, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], UV-filter, EC No 204-260-8, scientific opinion, homosalate
Abstract

International audience; Conclusion of the opinion:1. In light of the data provided and taking under consideration the concerns related to potential endocrine disrupting properties of homosalate, does the SCCS consider homosalate safe when used as a UV-filter in cosmetic products up to a maximum concentration of 10 %?On the basis of safety assessment of homosalate, and considering the concerns related to potential endocrine disrupting properties, the SCCS has concluded that homosalate is not safe when used as a UV-filter in cosmetic products at concentrations of up to 10%.2. Alternatively, what is according to the SCCS, the maximum concentration considered safe for use of homosalate as a UV-filter in cosmetic products?In the SCCS’s opinion, the use of homosalate as a UV filter in cosmetic products is safe for the consumer up to a maximum concentration of 0.5% homosalate in the final product.3. Does the SCCS have any further scientific concerns with regard to the use of homosalate in cosmetic products?It needs to be noted that the SCCS has regarded the currently available evidence for endocrine disrupting properties of homosalate as inconclusive, and at best equivocal. This applies to all of the available data derived from in silico modelling, in vitro tests and in vivo studies, when considered individually or taken together. The SCCS considers that, whilst there are indications from some studies to suggest that homosalate may have endocrine effects, the evidence is not conclusive enough at present to enable deriving a specific endocrine-related toxicological point of departure for use in safety assessment.Exposure to homosalate from other products than those in this Opinion has not been considered.Combined exposure to salicylic acid either formed by metabolic transformation from homosalate, other salicylates (e.g. methylsalicylate) or directly from salicylic acid itself has not been considered in this opinion.The use of Homosalate at the lower concentrations may have a bearing on efficacy as UV-filter, however this is outside the SCCS remit to assess the efficacy of cosmetic ingredients.Keywords: SCCS, scientific opinion, homosalate, UV-filter, Regulation 1223/2009, CAS No 118-56-9, EC No 204-260-8Opinion to be cited as:SCCS (Scientific Committee on Consumer Safety), Opinion on homosalate (CAS No 118-56-9, EC No 204-260-8), preliminary version of 27-28 October 2020, final version of 24-25 June 2021, SCCS/1622/20.

Published
2021

10. SCCS OPINION on Acid Yellow 3 – C054 (CAS No. 8004-92-0, EC. No 305-897-5) - Submission II - SCCS/1631/21 – Preliminary Version

Author

Bernauer, Ulrike, Bodin, Laurent, Chaudhry, Qasim, Coenraads, Pieter J., Dusinska, Maria, Ezendam, Janine, Gaffet, Eric, Galli, Corrado Lodovico, Granum, Berit Brunstad, Panteri, Eirini, Rogiers, Vera, Rousselle, Christophe, Stepnik, Maciej, Vanhaecke, Tamara, Wijnhoven, Susan, Koutsodimou, Aglaia, Uter, Wolfgang, von Götz, Natalie, German Federal Institute for Risk Assessment [Berlin] (BfR), Scientific Committee for Consumer Safety (SCCS) (SCCS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of Chester, University Medical Center Groningen [Groningen] (UMCG), Norwegian Institute for Air Research (NILU), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Institut Jean Lamour (IJL), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano = University of Milan (UNIMI), Norwegian Institute of Public Health [Oslo] (NIPH), National and Kapodistrian University of Athens (NKUA), Vrije Universiteit Brussel (VUB), Direction des affaires européennes et internationales (DAEI), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), QSAR lab, General Chemical State Laboratory (GCSL), University Hospital Erlangen = Uniklinikum Erlangen, Swiss Federal Office of Public Health, Scientific Committee for Consumer Safety (European Commission), Université de Lorraine (UL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Milan, University-Hospital Erlangen, University of Erlangen-Nuremberg - Universität tsstr. 21-23, 91054 Erlangen DE, and Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)

Subjects
Acid Yellow 3, hair dye, SCCS, CAS Number 8004-92-0, Regulation 1223/2009, EC No 305-897-5, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], scientific opinion
Abstract

International audience; SCCS OPINION on Acid Yellow 3 – C054 (CAS No. 8004-92-0, EC. No 305-897-5) - Submission II - SCCS/1631/21 – Preliminary VersionU. Bernauer, L. Bodin, Q. Chaudhry, P.J. Coenraads, M. Dusinska, J. Ezendam, E. Gaffet, C. L. Galli, B. Granum, E. Panteri, V. Rogiers, Ch. Rousselle, M. Stepnik, T. Vanhaecke, S. Wijnhoven, A. Koutsodimou, W. Uter, N. von GötzThe SCCS adopted this document by written procedure on 7 May 2021 (32 Pages)Mise en ligne 10 Mai 2021 https://ec.europa.eu/health/sites/default/files/scientific_committees/consumer_safety/docs/sccs_o_253.pdfOn request from: European CommissionSCCS Number: SCCS/1631/21Adopted on: 7 May 2021Conclusion of the opinion: (1) In light of the data provided, does the SCCS consider Acid Yellow 3, safe when used in non-oxidative hair colouring products up to a maximum on-head concentration of 0.5 %?Based on the data provided in the dossier, the SCCS considers that Acid Yellow 3 is safe when used in non-oxidative hair colouring products at on-head concentrations of up to 0.5%. (2) Does the SCCS have any further scientific concerns with regard to the use of Acid Yellow 3 in cosmetic products?A detailed analytical report on the test substance in representative batches and results of the stability tests should be provided to exclude the possibility of the presence of any impurities that may be of concern.Keywords:SCCS, scientific opinion, Acid Yellow 3, hair dye, Regulation 1223/2009, CAS Number 8004-92-0, EC No 305-897-5Opinion to be cited as:SCCS (Scientific Committee on Consumer Safety), Opinion on Acid Yellow 3 – C054 (CAS Number 8004-92-0, EC No 305-897-5), submission II, preliminary version of 7 May 2021, SCCS/1631/21.

Published
2021

11. SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) - SCCS/1625/20 - Final Opinion

Author

Bernauer, U., Bodin, L., Chaudhry, Q., Coenraads, P.J., Dusinska, M., Ezendam, J., Gaffet, E., Galli, C. L., Granum, B., Panteri, E., Rogiers, V., Rousselle, Ch., Stepnik, M., Vanhaecke, T., Wijnhoven, S., Koutsodimou, A., Uter, W., Goetz, N. Von, German Federal Institute for Risk Assessment [Berlin] (BfR), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Scientific Committee for Consumer Safety (SCCS) (SCCS), University of Chester, University Medical Center Groningen [Groningen] (UMCG), Norwegian Institute for Air Research (NILU), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Institut Jean Lamour (IJL), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano = University of Milan (UNIMI), Norwegian Institute of Public Health [Oslo] (NIPH), National and Kapodistrian University of Athens (NKUA), Vrije Universiteit Brussel (VUB), Direction des affaires européennes et internationales (DAEI), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), QSAR lab, General Chemical State Laboratory (GCSL), University Hospital Erlangen = Uniklinikum Erlangen, Swiss Federal Office of Public Health, Scientific Committee for Consumer Safety (European Commission), Université de Lorraine (UL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Milan, University-Hospital Erlangen, University of Erlangen-Nuremberg - Universität tsstr. 21-23, 91054 Erlangen DE, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), and Publications Office of the European Union

Subjects
SCCS, Benzophenone-3, Regulation 1223/2009, EC No 205-031-5, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], CAS Number 131-57-7, scientific opinion, UV filter
Abstract

International audience; Conclusion of the opinion:(1) In light of the data provided and taking under consideration the concerns related to potential endocrine disrupting properties of Benzophenone-3, does the SCCS consider Benzophenone-3 safe when used as a UV-filter in cosmetic products up to a maximum concentration of 6% and up to 0.5% in cosmetic products to protect product formulation?On the basis of safety assessment, and considering the concerns related to potential endocrine disrupting properties of benzophenone-3 (BP-3), the SCCS has concluded that:a. The use of BP-3 as a UV-filter up to a maximum concentration of 6% in sunscreen products, either in the form of body cream, sunscreen propellant spray or pump spray, is not safe for the consumer.b. The use of BP-3 as a UV-filter up to a maximum concentration of 6% in face cream, hand cream, and lipsticks is safe for the consumer.c. The use of BP-3 up to 0.5% in cosmetic products to protect the cosmetic formulation is safe for the consumer.(2) Alternatively, what is according to the SCCS the maximum concentration considered safe for use of Benzophenone-3 as a UV-filter in cosmetic products?In the SCCS’s opinion, the use of BP-3 as a UV filter in the following sunscreen products is safe for the consumer up to a maximum concentration of:a. 2.2% in body creams, in propellant sprays and in pump sprays, provided that there is no additional use of BP-3 at 0.5% in the same formulation for protecting the cosmetic formulation.b. Where BP-3 is also used at 0.5% in the same formulation, the levels of BP-3 used as UV filter should not exceed 1.7% in body creams, in propellant sprays and in pump sprays.(3) Does the SCCS have any further scientific concerns with regard to the use of Benzophenone-3 in cosmetic products?It needs to be noted that the SCCS has regarded the currently available evidence for endocrine disrupting properties of BP-3 as inconclusive, and at best equivocal. This applies to all of the available data derived from in silico modelling, in vitro tests and in vivo studies, either considered individually or taken together. The SCCS considers that, whilst there are indications from some studies to suggest that BP-3 may have endocrine effects, the overall evidence is not conclusive enough at present for the SCCS to ascertain whether or not BP-3 is an ED substance, and this warrants further investigations.The SCCS mandates do not address environmental aspects. Therefore, this assessment did not cover the safety of BP-3 for the environment.Opinion to be cited as:SCCS (Scientific Committee on Consumer Safety), Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5), preliminary version of 15 December 2020, final version of 30-31 March 2021, SCCS/1625/20.

Published
2021

12. SCCS OPINION on Resorcinol- SCCS/1619/20 - Final Opinion

Author

Bernauer, Ulrike, Bodin, Laurent, Chaudhry, Qasim, Coenraads, Pieter J., Dusinska, Maria, Ezendam, Janine, Gaffet, Eric, Galli, Corrado Lodovico, Granum, Berit Brunstad, Panteri, Eirini, Rogiers, Vera, Rousselle, Christophe, Stepnik, Maciej, Vanhaecke, Tamara, Wijnhoven, Susan, Koutsodimou, Aglaia, Uter, Wolfgang, von Götz, Natalie, German Federal Institute for Risk Assessment [Berlin] (BfR), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Scientific Committee for Consumer Safety (SCCS) (SCCS), University of Chester, University Medical Center Groningen [Groningen] (UMCG), Norwegian Institute for Air Research (NILU), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Institut Jean Lamour (IJL), Université de Lorraine (UL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Milan, Norwegian Institute of Public Health [Oslo] (NIPH), National and Kapodistrian University of Athens (NKUA), Vrije Universiteit Brussel (VUB), Direction des affaires européennes et internationales (DAEI), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), QSAR lab, General Chemical State Laboratory (GCSL), University-Hospital Erlangen, University of Erlangen-Nuremberg - Universität tsstr. 21-23, 91054 Erlangen DE, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Swiss Federal Office of Public Health, Scientific Committee for Consumer Safety (European Commission), Gaffet, Eric, Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Scientific Committee for Consumer Safety (SCCS), Publications Office of the European Union, Università degli Studi di Milano = University of Milan (UNIMI), and University Hospital Erlangen = Uniklinikum Erlangen

Subjects
hair dye, stomatognathic diseases, SCCS, Resorcinol, EC No 203-585-2, integumentary system, Regulation 1223/2009, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], CAS Number 108-46-3, [PHYS.COND.CM-MS] Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], scientific opinion
Abstract

International audience; Conclusion of the opinion:1/ In light of the data provided and taking under consideration the concerns related to potential endocrine disrupting properties of Resorcinol, does the SCCS consider Resorcinol safe when used as an oxidative hair dye in products intended for hair and eyelashes up to 1.25 % and up to 0.5 % in hair lotions and shampoos?Keeping in view the evidence on endocrine disrupting properties of resorcinol, the SCCS assessment shows that resorcinol is safe when used as an oxidative hair dye in products intended for hair and eyelashes up to 1.25 % and up to 0.5 % in hair lotions and shampoos.2/ Alternatively, what is according to the SCCS, the maximum concentration considered safe for use of Resorcinol as an oxidative hair dye in products intended for hair and eyelashes and for hair lotions and shampoos?/3/ Does the SCCS have any further scientific concerns with regard to the use of Resorcinol in cosmetic products?Resorcinol is a moderate skin sensitiser based on data from animal studies. Clinical studies show that the frequency of contact sensitisation in humans is low.The SCCS mandates do not address environmental aspects. Therefore, this assessment did not cover the safety of resorcinol for the environment.Opinion to be cited as:SCCS (Scientific Committee on Consumer Safety), Opinion on Resorcinol (CAS No 108-46-3, EC No 203-585-2), preliminary version of 16 October 2020, final version of 30-31 March 2021, SCCS/1619/20

Published
2021

13. SCCS OPINION ON Propylparaben - SCCS/1623/20 - Final Opinion

Author

Bernauer, U., Bodin, L., Chaudhry, Q., Coenraads, P.J., Dusinska, M., Ezendam, J., Gaffet, E., Galli, C. L., Granum, B., Panteri, E., Rogiers, V., Rousselle, Ch., Stepnik, M., Vanhaecke, T., Wijnhoven, S., Koutsodimou, A., Simonnard, A., Uter, W., Goetz, N. Von, German Federal Institute for Risk Assessment [Berlin] (BfR), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Scientific Committee for Consumer Safety (SCCS) (SCCS), University of Chester, University Medical Center Groningen [Groningen] (UMCG), Norwegian Institute for Air Research (NILU), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Institut Jean Lamour (IJL), Université de Lorraine (UL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Milan, Norwegian Institute of Public Health [Oslo] (NIPH), National and Kapodistrian University of Athens (NKUA), Vrije Universiteit Brussel (VUB), Direction des affaires européennes et internationales (DAEI), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), QSAR lab, General Chemical State Laboratory (GCSL), Institut national de recherche et de sécurité (Paris) (INRS (Paris)), University-Hospital Erlangen, University of Erlangen-Nuremberg - Universität tsstr. 21-23, 91054 Erlangen DE, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Swiss Federal Office of Public Health, Scientific Committee for Consumer Safety (European Commission), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano = University of Milan (UNIMI), University Hospital Erlangen = Uniklinikum Erlangen, Scientific Committee for Consumer Safety (SCCS), and Publications Office of the European Union

Subjects
EC No 202-307-7, SCCS, Regulation 1223/2009, preservative, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], CAS No 94-13-3, scientific opinion, Propylparaben
Abstract

International audience; Conclusion of the opinion:1. In light of the data provided and taking under consideration the concerns related to potential endocrine disrupting properties of Propylparaben, does the SCCS consider Propylparaben safe when used as a preservative in cosmetic products up to a maximum concentration of 0.14 %?On the basis of the safety assessment of Propylparaben, and considering the concerns related to potential endocrine disrupting properties, the SCCS has concluded that propylparaben is safe when used as a preservative in cosmetic products up to a maximum concentration of 0.14 %.2. Alternatively, what is according to the SCCS, the maximum concentration considered safe for use of Propylparaben as a preservative in cosmetic products?/3. Does the SCCS have any further scientific concerns with regard to the use of Propylparaben in cosmetic products?The available data on Propylparaben provide some indications for potential endocrine effects. However, the current level of evidence is not sufficient to regard it as an endocrine disrupting substance, or to derive a toxicological point of departure based on endocrine disrupting properties for use in human health risk assessment.The SCCS mandates do not address environmental aspects. Therefore, this assessment did not cover the safety of propylparaben for the environment.Opinion to be cited as:SCCS (Scientific Committee on Consumer Safety), Opinion on Propylparaben (CAS No 94-13-3, EC No 202-307-7), preliminary version of 27-28 October 2020, final version of 30-31 March 2021, SCCS/1623/20.

Published
2021

14. Final Opinion on the safety of presence of BPA in clothing articles : Results of the public consultation

Author

Bernauer, Ulrike, Bodin, Laurent, Chaudhry, Qasim, Coenraads, Pieter J., Dusinska, Maria, Ezendam, Janine, Gaffet, Eric, Galli, Corrado Lodovico, Granum, Berit Brunstad, Panteri, Eirini, Rogiers, Vera, Rousselle, Christophe, Stepnik, Maciej, Vanhaecke, Tamara, Wijnhoven, Susan, Koutsodimou, Aglaia, Uter, Wolfgang, von Götz, Natalie, German Federal Institute for Risk Assessment [Berlin] (BfR), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Scientific Committee for Consumer Safety (SCCS) (SCCS), University of Chester, University Medical Center Groningen [Groningen] (UMCG), Norwegian Institute for Air Research (NILU), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Institut Jean Lamour (IJL), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano = University of Milan (UNIMI), Norwegian Institute of Public Health [Oslo] (NIPH), National and Kapodistrian University of Athens (NKUA), Vrije Universiteit Brussel (VUB), Direction des affaires européennes et internationales (DAEI), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), QSAR lab, General Chemical State Laboratory (GCSL), University Hospital Erlangen = Uniklinikum Erlangen, Swiss Federal Office of Public Health, Scientific Committee for Consumer Safety (European Commission), Université de Lorraine (UL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Milan, University-Hospital Erlangen, University of Erlangen-Nuremberg - Universität tsstr. 21-23, 91054 Erlangen DE, and Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)

Subjects
[PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci]
Abstract

International audience; The European Commission and its Scientific Committee on Consumer Safety (SCCS) published the final Opinion on the safety of presence of BPA in clothing articles.A public consultation on the preliminary Opinion on the safety of presence of BPA in clothing articles was open on the website of the Scientific Committees from 16 October to 7 December 2020. Information about the public consultation was broadly communicated to national authorities, international organisations and other stakeholders. The SCCS received 25 comments from six different interested parties.Each comment and reference submitted during this time was carefully considered by the SCCS. Where appropriate, the text of the relevant sections of the Opinion was edited or explanations were added to pertinent comments. The literature list has been updated with relevant publications

Published
2021

15. SCIENTIFIC ADVICE on the safety of nanomaterials in cosmetics (SCCS) - SCCS/1618/2020 – Final Advice - Corrigendum of 8 March 2021

Author

Bernauer, Ulrike, Bodin, Laurent, Chaudhry, Qasim, Coenraads, Pieter J., Dusinska, Maria, Gaffet, Eric, Panteri, Eirini, Rousselle, Christophe, Stepnik, Maciej, Wijnhoven, Susan, de Jong, Wolfgang, von Götz, Natalie, Bundesinstitut für Risikobewertung - Federal Institute for Risk Assessment (BfR), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Scientific Committee for Consumer Safety (SCCS) (SCCS), University of Chester, University Medical Center Groningen [Groningen] (UMCG), Norwegian Institute for Air Research (NILU), Institut Jean Lamour (IJL), Université de Lorraine (UL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), National and Kapodistrian University of Athens (NKUA), Direction des affaires européennes et internationales (DAEI), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), QSAR lab, National Institute for Public Health and the Environment [Bilthoven] (RIVM), University-Hospital Erlangen, University of Erlangen-Nuremberg - Universität tsstr. 21-23, 91054 Erlangen DE, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Swiss Federal Office of Public Health, Scientific Committee for Consumer Safety (SCCS, European Commission), Scientific Committee for Consumer Safety (European Commission), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), and University Hospital Erlangen = Uniklinikum Erlangen

Subjects
Safety Assessment, Scientific advice, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], Cosmetics, Nanomaterials, Regulation
Abstract

International audience; The SCCS adopted this Advice by written procedure on 8 January 2021 - Corrigendum of 8 March 2021 The SCCS concludes the following:1. The SCCS is requested to determine the nanomaterials, as published in the recent catalogue of nanomaterials of 2019, for which specific concerns can be identified and justified in order to establish a priority list of nanomaterials for risk assessment (Article 16(4) Reg.1223/2009). More specifically, the SCCS is requested to provide a description of the specific concerns that have been identified for the nanomaterials mentioned above. This process should be based on the currently available scientific literature and SCCS’ expert judgement.*Through a review of the available information and expert judgment, the SCCS has identified certain aspects of nanomaterials that constitute a basis for concern over safety to consumers’ health when used in cosmetic products. These include:• Physicochemical aspects relating to: very small dimensions of the constituent particles; solubility/persistence; chemical nature and toxicity of the nanomaterial; physical/morphological features of the constituent particles; surface chemistry and surface characteristics (surface modifications/coatings);• Exposure aspects relating to: the frequency and the amounts used, whether the number/type of consumer product(s) used is relatively high; and whether there is a potential for systemic exposure of the consumer to nanoparticles and potential accumulation in the body;• Other aspects relating to: novel properties, activity or function, and specific concern arising from the type of application.A detailed account of these aspects has been presented in this Advice. Also, the nanomaterials listed in the EC catalogue of nanomaterials of 2019 have been tabulated in an order of priority according to risk potential in Annex 1 of this Advice.2. For the nanomaterials with inconclusive SCCS opinions, such as [Colloidal Silver (nano) (SCCS/1596/18), Styrene/Acrylates copolymer (nano) + Sodium styrene/Acrylates copolymer (nano) (SCCS/1595/18) and Silica, Hydrated Silica, and Silica Surface Modified with Alkyl Silylates (nano form) (SCCS/1545/15)], the SCCS is requested to assess if a potential risk can be identified according to Article 16(6) Reg. 1223/2009. Such assessment, regardless of the data previously submitted by the respective applicants, should be based on the available scientific literature and SCCS’ expert judgement (i.e. systemic or local availability; harmful effects specifically related to nano-form; surface catalysed reactions in nano-form, absorption (or potential absorption) from dermal and inhalation routes, potential of nano-form to deliver ionic forms, etc.).*The SCCS has reviewed previous inconclusive opinions on three nanomaterials (SCCS/1596/18; SCCS/1595/18 and SCCS/1545/15), in conjunction with any further relevant information available in published literature to identify whether there is a scientific basis for concern over their safety to consumers’ health when used in cosmetic products. The SCCS has identified certain aspects relating to each of the nanomaterials that raise a safety concern. These have been detailed in three separate annexes (2, 3 and 4) to this Advice.

Published
2021

16. SCCS OPINION ON Octocrylene - SCCS/1627/21- Preliminary Opinion

Author

Bernauer, Ulrike, Bodin, Laurent, Chaudhry, Qasim, Coenraads, Pieter J., Dusinska, Maria, Ezendam, Janine, Gaffet, Eric, Galli, Corrado Lodovico, Granum, Berit Brunstad, Panteri, Eirini, Rogiers, Vera, Rousselle, Christophe, Stepnik, Maciej, Vanhaecke, Tamara, Wijnhoven, Susan, Koutsodimou, Aglaia, Uter, Wolfgang, von Götz, Natalie, German Federal Institute for Risk Assessment [Berlin] (BfR), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Scientific Committee for Consumer Safety (SCCS) (SCCS), University of Chester, University Medical Center Groningen [Groningen] (UMCG), Norwegian Institute for Air Research (NILU), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Institut Jean Lamour (IJL), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano = University of Milan (UNIMI), Norwegian Institute of Public Health [Oslo] (NIPH), National and Kapodistrian University of Athens (NKUA), Vrije Universiteit Brussel (VUB), Direction des affaires européennes et internationales (DAEI), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), QSAR lab, General Chemical State Laboratory (GCSL), University Hospital Erlangen = Uniklinikum Erlangen, Swiss Federal Office of Public Health, Scientific Committee for Consumer Safety (European Commission), Université de Lorraine (UL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Milan, University-Hospital Erlangen, University of Erlangen-Nuremberg - Universität tsstr. 21-23, 91054 Erlangen DE, and Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)

Subjects
Octocrylene, SCCS, Regulation 1223/2009, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], UV-filter, EC No 228-250-8, scientific opinion, CAS No 6197-30-4
Abstract

International audience; "SCCS OPINION ON Octocrylene"SCCS/1627/21- Preliminary OpinionU. Bernauer, L. Bodin, Q. Chaudhry, P.J. Coenraads, M. Dusinska, J. Ezendam, E. Gaffet, C. L. Galli, B. Granum, E. Panteri, V. Rogiers, Ch. Rousselle, M. Stepnik, T. Vanhaecke, S. Wijnhoven, A. Koutsodimou, W. Uter, N. von GoetzThe SCCS adopted this document by written procedure on 15 January 2021 (47 Pages)Mise en ligne 18 January 2021https://ec.europa.eu/health/sites/health/files/scientific_committees/consumer_safety/docs/sccs_o_249.pdfSCCS members: U. Bernauer, L. Bodin, Q. Chaudhry (Rapporteur), P.J. Coenraads (Chairperson), M. Dusinska, J. Ezendam, E. Gaffet, C. L. Galli, B. Granum (Rapporteur), E. Panteri, V. Rogiers, Ch. Rousselle, M. Stepnik, T. Vanhaecke, S. WijnhovenSCCS external expert: A. Koutsodimou, W. Uter, N. von Goetz (Rapporteur)Contact: SANTE-C2-SCCS@ec.europa.euOn request from: European CommissionSCCS Number: SCCS/1627/21Adopted on: 15 January 2021Conclusion of the opinion:1. In light of the data provided and taking under consideration the concerns related to potential endocrine disrupting properties of Octocrylene, does the SCCS consider Octocrylene safe when used as a UV-filter in cosmetic products up to a maximum concentration of 10% (as acid)?On the basis of safety assessment, and considering the concerns related to potential endocrine disrupting properties of Octocrylene (CAS No 6197-30-4), the SCCS considers that it is safe at concentrations of up to 10% when used individually or together as a UV-filter in cosmetic products, i.e. in sunscreen cream/lotion, sunscreen pump spray, face cream, hand cream and lipstick.Also, the use of sunscreen propellant spray is considered safe at concentrations of up to 10% when used individually but not safe when used together with face cream, hand cream, and lipstick.2. Alternatively, what is according to the SCCS the maximum concentration considered safe for use of Octocrylene as a UV-filter in cosmetic products?The use of Octocrylene in sunscreen propellant spray is considered safe when its concentration does not exceed 9% when used together with face cream, hand cream and lipstick containing 10% Octocrylene.3. Does the SCCS have any further scientific concerns with regard to the use of Octocrylene in cosmetic products?The SCCS considers that, whilst there are indications from some in vivo studies to suggest that Octocrylene may have endocrine effects, the evidence is not conclusive enough at present to enable deriving a specific endocrine-related toxicological point of departure for use in safety assessment.Contact sensitisation to Octocrylene has been reported, however, taking into consideration the widespread use of Octocrylene in cosmetic products, the number of reported cases of allergic contact dermatitis appears to be negligible.It should be noted that occurrence of photoallergy to Octocrylene is strongly related to a previous photoallergy to topical ketoprofen. Exposure to Octocrylene from other products than those in this Opinion has not been considered.Keywords:SCCS, scientific opinion, Octocrylene, UV-filter, Regulation 1223/2009, CAS No 6197-30-4, EC No 228-250-8Opinion to be cited as:SCCS (Scientific Committee on Consumer Safety), Opinion on Octocrylene (CAS No 6197-30-4, EC No 228-250-8), preliminary version of 15 January 2021, SCCS/1627/21.

Published
2021

17. Making sense of missense variants in TTN-related congenital myopathies

Author

Anna Sarkozy, Erik-Jan Kamsteeg, Mark Pfuhl, Nicol C. Voermans, Martin Rees, Corrie E. Erasmus, Hülya-Sevcan Daimagüler, Steven A. Moore, Rahul Phadke, Mark R. Holt, Rolf Schröder, Istvan Bodi, Carla Grosmann, Sebahattin Cirak, E. Matthews, Ay Lin Kho, Peter Van den Bergh, Christian Thiel, Shane McKee, Joel Victor Fluss, Roksana Nikoopour, Charu Deshpande, Jens Reimann, Emily C. Oates, Maria Elena Farrugia, Özkan Özdemir, Isabelle Richard, Cristina Domínguez-González, Chaminda Konersman, Ekkehard Wilichowski, Birgit Brandmeier, Atsushi Fukuzawa, Ana Ferreiro, Heinz Jungbluth, Ros Quinlivan, Sandya Tirupathi, Mathias Gautel, Gabriele Dekomien, Cheryl Longman, Miguel A Fernandez-Garcia, Francesco Muntoni, Michael G. Hanna, Elizabeth Wraige, Elke Hobbiebrunken, Sarah Grover, UCL - SSS/IONS - Institute of NeuroScience, UCL - (SLuc) Service de neurologie, UCL - (SLuc) Centre de référence neuromusculaire, King‘s College London, Evelina London Children's Hospital, Guy's Hospital [London], University of Cologne, Children’s University Hospital of Geneva [Switzerland], Queen Elizabeth University Hospital (Glasgow), National Hospital for Neurology and Neurosurgery [London, UK], Great Ormond Street Hospital for Children [London] (GOSH), University College of London [London] (UCL), University of New South Wales [Sydney] (UNSW), Westmead Hospital [Sydney], University Hospital Erlangen [Germany], Universitätsklinikum Erlangen [Erlangen], University of Bonn Medical Centre [Bonn], Radboud university [Nijmegen], Rady Children's Hospital, Belfast City Hospital, Royal Belfast Hospital for Sick Children, University of Iowa [Iowa City], University of Göttingen - Georg-August-Universität Göttingen, Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, Généthon, Saint-Luc University Hospital [Brussels, Belgium], Hospital Universitario 12 de Octubre [Madrid], Université de Paris (UP), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), King's College Hospital (KCH), MRC Centre for Neuromuscular Diseases [London, UK], University Hospital Erlangen = Uniklinikum Erlangen, Radboud University [Nijmegen], Radboud University Medical Center [Nijmegen], Gillette Children's Specialty Healthcare [St Paul], Georg-August-University = Georg-August-Universität Göttingen, Ruhr-Universität Bochum [Bochum], Université Paris Cité (UPCité), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)

Subjects
Adult, Male, 0301 basic medicine, Weakness, Adolescent, Myotonia Congenita, Mutation, Missense, Other Research Donders Center for Medical Neuroscience [Radboudumc 0], Extraocular muscles, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], Pathology and Forensic Medicine, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Humans, Medicine, Missense mutation, Connectin, Child, Myopathy, Aged, Muscle contracture, Genetics, Phenocopy, Original Paper, biology, business.industry, Infant, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Middle Aged, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], medicine.disease, Congenital myopathy, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Child, Preschool, biology.protein, Female, Titin, Neurology (clinical), medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract

Mutations in the sarcomeric protein titin, encoded byTTN, are emerging as a common cause of myopathies. The diagnosis of aTTN-related myopathy is, however, often not straightforward due to clinico-pathological overlap with other myopathies and the prevalence ofTTNvariants in control populations. Here, we present a combined clinico-pathological, genetic and biophysical approach to the diagnosis ofTTN-related myopathies and the pathogenicity ascertainment ofTTNmissense variants. We identified 30 patients with a primaryTTN-related congenital myopathy (CM) and two truncating variants, or one truncating and one missenseTTNvariant, or homozygous for oneTTNmissense variant. We found that TTN-related myopathies show considerable overlap with other myopathies but are strongly suggested by a combination of certain clinico-pathological features. Presentation was typically at birth with the clinical course characterized by variable progression of weakness, contractures, scoliosis and respiratory symptoms but sparing of extraocular muscles. Cardiac involvement depended on the variant position. Our biophysical analyses demonstrated that missense mutations associated with CMs are strongly destabilizing and exert their effect when expressed on a truncating background or in homozygosity. We hypothesise that destabilizingTTNmissense mutations phenocopy truncating variants and are a key pathogenic feature of recessive titinopathies that might be amenable to therapeutic intervention.

Published
2021

18. ADDENDUM to the scientific opinion SCCS/1613/19 on the safety of aluminium in cosmetic products (lipstick) - Submission II - SCCS/1626/20 - Addendum (lipstick) – Final version

Author

Coenraads, Pieter J., Rogiers, Vera, Chaudhry, Qasim, Bodin, Laurent, Bernauer, Ulrike, Dusinska, Maria, Ezendam, Janine, Gaffet, Eric, Galli , Lodovico Corrado, Granum , Berit Brunstad, Panteri, Eirini, Rousselle, Christophe, Stępnik, Maciej, Vanhaecke, Tamara, Wijnhoven, Susan, Koutsodimou, Aglaia, Uter, Wolfgang, Götz, Natalie von, Gaffet, Eric, Scientific Committee for Consumer Safety (European Commission), University Medical Center Groningen [Groningen] (UMCG), Vrije Universiteit Brussel (VUB), University of Chester, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Scientific Committee for Consumer Safety (SCCS) (SCCS), German Federal Institute for Risk Assessment [Berlin] (BfR), Norwegian Institute for Air Research (NILU), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Institut Jean Lamour (IJL), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano = University of Milan (UNIMI), Norwegian Institute of Public Health [Oslo] (NIPH), National and Kapodistrian University of Athens (NKUA), Direction des affaires européennes et internationales (DAEI), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), QSAR lab, General Chemical State Laboratory (GCSL), University Hospital Erlangen = Uniklinikum Erlangen, Swiss Federal Office of Public Health, Université de Lorraine (UL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Milan, University-Hospital Erlangen, University of Erlangen-Nuremberg - Universität tsstr. 21-23, 91054 Erlangen DE, and Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)

Subjects
Lipstick, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], Aluminium, Scientific opinion, [PHYS.COND.CM-MS] Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci]
Abstract

International audience; Conclusion of the opinion:1. In light of the new data provided, does the SCCS consider Aluminium safe when used in lipsticks up to a maximum concentration of 14%? In the event that the estimated exposure to Aluminium from lipsticks of cosmetic products is found to be of concern, SCCS is asked to recommend safe concentration limits.In the light of the new data provided, the SCCS considers that the use of aluminium compounds is safe at the following equivalent aluminium concentrations up to:· 6.25% in non-spray deodorants or non-spray antiperspirants·10.60% in spray deodorants or spray antiperspirants·2.65% in toothpaste and·14% in lipstick2. Does the SCCS have any further scientific concerns regarding the use of Aluminium substances in cosmetic products taking into account the newly submitted information on aggregate exposure from cosmetics?The SCCS considers that the systemic exposure to aluminium via daily applications of cosmetic products does not add significantly to the systemic body burden of aluminium from other sources. Exposure to aluminium may also occur from sources other than cosmetic products, and a major source of aluminium in the population is the diet. This assessment has not taken into account the daily dietary intake of aluminium.Keywords:SCCS, scientific opinion, aluminium, addendum, lipstick, Regulation 1223/2009Opinion to be cited as:SCCS (Scientific Committee on Consumer Safety), Addendum to the scientific opinion SCCS/1613/19 on the safety of aluminium in cosmetic products - Submission II, preliminary version of 15 December 2020, final version of 30-31 March 2021, SCCS/1626/20.

Published
2021

19. SCCS SCIENTIFIC ADVICE ON on the threshold for the warning ‘contains formaldehyde’ in Annex V, preamble point 2 for formaldehyde-releasing substances - SCCS/1632/21– Scientific advice

Author

Bernauer, Ulrike, Bodin, Laurent, Chaudhry, Qasim, Coenraads, Pieter J., Dusinska, Maria, Ezendam, Janine, Gaffet, Eric, Galli, Corrado Lodovico, Granum, Berit Brunstad, Panteri, Eirini, Rogiers, Vera, Rousselle, Christophe, Stepnik, Maciej, Vanhaecke, Tamara, von Götz, Natalie, Wijnhoven, Susan, Koutsodimou, Aglaia, Uter, Wolfgang, Gaffet, Eric, Scientific Committee for Consumer Safety (European Commission), German Federal Institute for Risk Assessment [Berlin] (BfR), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Scientific Committee for Consumer Safety (SCCS) (SCCS), University of Chester, University Medical Center Groningen [Groningen] (UMCG), Norwegian Institute for Air Research (NILU), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Institut Jean Lamour (IJL), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano = University of Milan (UNIMI), Norwegian Institute of Public Health [Oslo] (NIPH), National and Kapodistrian University of Athens (NKUA), Vrije Universiteit Brussel (VUB), Direction des affaires européennes et internationales (DAEI), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), QSAR lab, Swiss Federal Office of Public Health, General Chemical State Laboratory (GCSL), University Hospital Erlangen = Uniklinikum Erlangen, Scientific Committee for Consumer Safety (SCCS), Publications Office of the European Union, Université de Lorraine (UL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Milan, University-Hospital Erlangen, University of Erlangen-Nuremberg - Universität tsstr. 21-23, 91054 Erlangen DE, and Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)

Subjects
SCCS, Regulation 1223/2009, Formaldehyde, CAS No. 50-00-0, SCCS/1632/21, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], EC No. 200-001-8, scientific advice, [PHYS.COND.CM-MS] Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci]
Abstract

International audience; SCCS SCIENTIFIC ADVICE ON on the threshold for the warning ‘contains formaldehyde’ in Annex V, preamble point 2 for formaldehyde-releasing substances - SCCS/1632/21– Scientific adviceU. Bernauer, L. Bodin, Q. Chaudhry, P.J. Coenraads, M. Dusinska, J. Ezendam, E. Gaffet, C. L. Galli, B. Granum, E. Panteri, V. Rogiers, Ch. Rousselle, M. Stepnik, T. Vanhaecke, N. von Götz, S. Wijnhoven, A. Koutsodimou, W. UterThe SCCS adopted this document by written procedure on 7 May 2021 (12 Pages)Mise en ligne 10 Mai 2021 https://ec.europa.eu/health/sites/default/files/scientific_committees/consumer_safety/docs/sccs_o_254.pdfOn request from: European CommissionSCCS Number: SCCS/1632/21Adopted on: 7 May 2021Conclusion of the opinion:1. In light of the data provided and taking under consideration the available scientific literature, does the SCCS consider the 0.05% threshold for labelling formaldehyde releasing substances adequate to protect consumers?The SCCS considers that the present threshold does not sufficiently protect consumers sensitised to formaldehyde from exposure to free formaldehyde from formaldehyde releasers.2. Does the SCCS consider necessary to change the 0.05% threshold and at which level?Reducing the present threshold by a factor of 50, that is, to 0.001% (10 ppm), will protect the vast majority of consumers sensitised to formaldehyde. This threshold applies to the total free formaldehyde irrespective of whether a product contains one or more formaldehyde releaser(s).Keywords:SCCS, scientific advice, formaldehyde, Regulation 1223/2009, CAS No. 50-00-0, EC No. 200-001-8, SCCS/1632/21Opinion to be cited as:SCCS (Scientific Committee on Consumer Safety), Scientific advice on the threshold for the warning ‘contains formaldehyde’ in Annex V, preamble point 2 for formaldehyde-releasing substances, final version of 7 May 2021, SCCS/1632/21.

Published
2021

20. Real-world experience of leadless left ventricular endocardial cardiac resynchronization therapy: A multicenter international registry of the WiSE-CRT pacing system

Author

Mauro Biffi, Jonathan M. Behar, David Keane, Martin Arnold, Sam Riahi, Igor Diemberger, Benjamin Sieniewicz, Pasquale Vergara, Lucas V.A. Boersma, Petr Neuzil, Christian Butter, Richard J. Schilling, Simon James, Christopher A. Rinaldi, Martin Seifert, Pascal Defaye, Anthony Chow, Jean Claude Deharo, Andrew J. Turley, Timothy R. Betts, St Thomas’ Hospital, Oxford University Hospitals NHS Trust, University of Oxford [Oxford], James Cook University Hospital, Immanuel Klinikum Bernau Herzzentrum Brandenburg, St. Antonius Ziekenhuis, Aalborg University Hospital, Na Homolce Hospital, Prague, Czech Republic., Policlinico S’Orsola, San Raffaele Hospital, University Hospital Erlangen, St Vincent's University Hospital, Centre Hospitalier Universitaire [Grenoble] (CHU), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département de Cardiologie [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM), St Bartholomew's Hospital, King‘s College London, WiSE-CRT, Cardiology, ACS - Heart failure & arrhythmias, University of Oxford, University Hospital Erlangen = Uniklinikum Erlangen, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Guieu, régis, Sieniewicz B.J., Betts T.R., James S., Turley A., Butter C., Seifert M., Boersma L.V.A., Riahi S., Neuzil P., Biffi M., Diemberger I., Vergara P., Arnold M., Keane D.T., Defaye P., Deharo J.-C., Chow A., Schilling R., Behar J., and Rinaldi C.A.

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Heart Ventricles, [SDV]Life Sciences [q-bio], Mean QRS Duration, Cardiac resynchronization therapy, Postmarketing surveillance, Heart failure, 030204 cardiovascular system & hematology, Ventricular Function, Left, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Physiology (medical), Internal medicine, Medicine, Humans, cardiovascular diseases, 030212 general & internal medicine, Cardiac Resynchronization Therapy Devices, Prospective Studies, Registries, Aged, Ejection fraction, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Nonresponder, Stroke Volume, Equipment Design, medicine.disease, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV] Life Sciences [q-bio], Treatment Outcome, Endocardial pacing, Operator training, Leadless pacing, cardiovascular system, Etiology, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Endocardium
Abstract

International audience; BACKGROUND Biventricular endocardial pacing (BiV ENDO) is a therapy for heart failure patients who cannot receive transvenous epicardial cardiac resynchronization therapy (CRT) or have not responded adequately to CRT. BiV ENDO CRT can be delivered by a new wireless LV ENDO pacing system (WiSE-CRT system; EBR Systems, Sunnyvale, CA), without the requirement for lifelong anticoagulation.OBJECTIVE The purpose of this study was to assess the safety and efficacy of the WiSE-CRT system during real-world clinical use in an international registry.METHODS Data were prospectively collected from 14 centers implanting the WiSE-CRT system as part of the WiCS-LV Post Market Surveillance Registry. (ClinicalTrials.gov Identifier: NCT02610673).RESULTS Ninety patients from 14 European centers underwent implantation with the WiSE-CRT system. Patients were predominantly male, age 68.2 +/- 10.5 years, left ventricular ejection fraction 30.6% +/- 8.9%, mean QRS duration 180.7 +/- 27.0 ms, and 40% with ischemic etiology. Successful implantation and delivery of BiV ENDO pacing was achieved in 94.4% of patients. Acute (

Published
2020

21. De novo mutations in the X-linked TFE3 gene cause intellectual disability with pigmentary mosaicism and storage disorder-like features

Author

Bertrand Isidor, Rami Abou Jamra, Virginie Carmignac, Yannis Duffourd, Helio Pedro, Eriko Koshimizu, Maja Hempel, Tobias Bartolomaeus, Martin Chevarin, Floor A. M. Duijkers, Maria J. Guillen Sacoto, Erin Torti, David Geneviève, David J. Harris, Valerie Loik Ramey, Klaske D. Lichtenbelt, Arthur Sorlin, Miriam Maik, Anne Guimier, Paul Kuentz, Tatjana Bierhals, Orly Elpeleg, Yoshiko Murakami, Laurence Faivre, Jean Baptiste Rivière, Jill Clayton-Smith, Laurent Pasquier, Yuichi Abe, Edgard Verdura, Aviva Fattal, Judith St-Onge, Daphné Lehalle, Joerg Betschinger, Krista Sondergaard-Schatz, Laurie Simone, Christa W. Habela, Ivon Cusco, Mieke M. van Haelst, Pierre Vabres, Laurence Duplomb, Magali Avila, Sakoto Miyakate, Koen L.I. van Gassen, Julien Thevenon, Eveline S. J. M. de Bont, Benjamin Cogné, Pia Zacher, Silvana van Koningsbruggen, Thibaud Jouan, Irene Valenzuela, Christel Thauvin-Robinet, Salvy-Córdoba, Nathalie, FHU TRANSLAD (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Génétique médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), GeneDx [Gaithersburg, MD, USA], National Center for Child Health and Development [Tokyo], University Hospital Leipzig, Manchester Centre for Genomic Medicine [Manchester, UK] (MCGM), St Mary's Hospital Manchester-Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester]-University of Manchester [Manchester]-Manchester University NHS Foundation Trust (MFT)-Faculty of Biology, Medicine and Health [Manchester, UK], University of Manchester [Manchester], Centre hospitalier universitaire de Nantes (CHU Nantes), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Vall d'Hebron University Hospital [Barcelona], University Medical Center Groningen [Groningen] (UMCG), VU University Medical Center [Amsterdam], Department of Genetics and Metabolic Diseases and the Monique and Jacques Roboh Department of Genetic Research, Hadassah Hebrew University Medical Center [Jerusalem], Tel Aviv Sourasky Medical Center [Te Aviv], Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Boston Children's Hospital, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Brain Centre Rudolf Magnus [Utrecht], University Medical Center [Utrecht], Hackensack University Medical Center [Hackensack], Yokohama City University (YCU), Osaka University [Osaka], CHU Pontchaillou [Rennes], Johns Hopkins University School of Medicine [Baltimore], Child Health and Human Development Program [Montréal, QC, Canada], McGill University Health Center [Montreal] (MUHC), Centre Hospitalier Universitaire [Grenoble] (CHU), University Hospital Erlangen = Uniklinikum Erlangen, Department of Clinical Genetics, Academic Medical Centre, Amsterdam, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), CIBER de Enfermedades Raras (CIBERER), Kleinwachau - Saxon Epilepsy Center Radeberg, Department of Human Genetics [Montréal], McGill University = Université McGill [Montréal, Canada], Friedrich Miescher Institute for Biomedical Research (FMI), Novartis Research Foundation, Human Genetics, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, and Amsterdam Reproduction & Development (AR&D)

Subjects
0301 basic medicine, MESH: Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Intellectual disability, TFE3, Biology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, MESH: Intellectual Disability, 03 medical and health sciences, Exon, 0302 clinical medicine, MESH: Whole Exome Sequencing, MESH: Child, Genetics, medicine, Missense mutation, Gene, Genetics (clinical), Exome sequencing, Pigmentary mosaicism, MESH: Pathology, Molecular, MESH: Adolescent, MESH: Humans, Alternative splicing, Lysosomal metabolism, MESH: Child, Preschool, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Adult, medicine.disease, Phenotype, MESH: Infant, MESH: Male, Storage disorder, 030104 developmental biology, MESH: Genes, X-Linked, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH: Young Adult, MESH: Epilepsy, MESH: Mosaicism, MESH: Pigmentation Disorders, MESH: Female, 030217 neurology & neurosurgery
Abstract

IntroductionPigmentary mosaicism (PM) manifests by pigmentation anomalies along Blaschko’s lines and represents a clue toward the molecular diagnosis of syndromic intellectual disability (ID). Together with new insights on the role for lysosomal signalling in embryonic stem cell differentiation, mutations in the X-linked transcription factor 3 (TFE3) have recently been reported in five patients. Functional analysis suggested these mutations to result in ectopic nuclear gain of functions.Materials and methodsSubsequent data sharing allowed the clustering of de novo TFE3 variants identified by exome sequencing on DNA extracted from leucocytes in patients referred for syndromic ID with or without PM.ResultsWe describe the detailed clinical and molecular data of 17 individuals harbouring a de novo TFE3 variant, including the patients that initially allowed reporting TFE3 as a new disease-causing gene. The 12 females and 5 males presented with pigmentation anomalies on Blaschko’s lines, severe ID, epilepsy, storage disorder-like features, growth retardation and recognisable facial dysmorphism. The variant was at a mosaic state in at least two male patients. All variants were missense except one splice variant. Eleven of the 13 variants were localised in exon 4, 2 in exon 3, and 3 were recurrent variants.ConclusionThis series further delineates the specific storage disorder-like phenotype with PM ascribed to de novo TFE3 mutation in exons 3 and 4. It confirms the identification of a novel X-linked human condition associated with mosaicism and dysregulation within the mechanistic target of rapamycin (mTOR) pathway, as well as a link between lysosomal signalling and human development.

Published
2020

22. Proceedings from the 3rd European Clinical Consensus Conference for clinical trials in device-based hypertension therapies

Author

Costas Tsioufis, Michael Böhm, David E. Kandzari, William Wijns, Faisal Sharif, Felix Mahfoud, Atul Pathak, Christian Ukena, Massimo Volpe, L. M. Ruilope, Gianfranco Parati, Sverre E. Kjeldsen, Markus P. Schlaich, Roland E. Schmieder, Atif Shahzad, Ajay J. Kirtane, Horst Sievert, Guido Grassi, Isabelle Durand Zaleski, Michael A. Weber, Michael Joner, John W. McEvoy, Michel Azizi, Gilles Chatellier, Sebastian Ewen, Peter J. Blankestijn, Andrew S.P. Sharp, Thomas F. Lüscher, Patrick Rossignol, Melvin D. Lobo, Michel Burnier, Massachusetts Institute of Technology (MIT), Universität des Saarlandes [Saarbrücken], CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Princesse Grace, Utrecht Brain Center [UMC], University Medical Center [Utrecht], Université de Lausanne = University of Lausanne (UNIL), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Deutsches Herzzentrum München (DHM), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Piedmont Heart Institute, Columbia University Irving Medical Center (CUIMC), Oslo University Hospital [Oslo], Queen Mary University of London (QMUL), Imperial College London, Universität Zürich [Zürich] = University of Zurich (UZH), National University of Ireland [Galway] (NUI Galway), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hospital Universitario 12 de Octubre [Madrid], The University of Western Australia (UWA), Baker Heart and Diabetes Institute (AUSTRALIA), University Hospital Galway, University Hospital of Wales (UHW), University of Exeter, Anglia Ruskin University (ARU), University of California [San Francisco] (UC San Francisco), University of California (UC), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), State University of New York (SUNY), University Hospital Erlangen = Uniklinikum Erlangen, National and Kapodistrian University of Athens (NKUA), HULOT, Jean-Sébastien, Mahfoud, F, Azizi, M, Ewen, S, Pathak, A, Ukena, C, Blankestijn, P, Böhm, M, Burnier, M, Chatellier, G, Durand Zaleski, I, Grassi, G, Joner, M, Kandzari, D, Kirtane, A, Kjeldsen, S, Lobo, M, Lüscher, T, Mcevoy, J, Parati, G, Rossignol, P, Ruilope, L, Schlaich, M, Shahzad, A, Sharif, F, Sharp, A, Sievert, H, Volpe, M, Weber, M, Schmieder, R, Tsioufis, C, and Wijns, W

Subjects
safety, medicine.medical_specialty, hypertension, [SDV]Life Sciences [q-bio], Calidad de vida, therapy, device, guidelines, Enfermedad cardiovascular, MEDLINE, 030204 cardiovascular system & hematology, medical devices, Consensus, Humans, Hypertension/drug therapy, Medical History Taking, 03 medical and health sciences, Tratamiento médico, 0302 clinical medicine, Hipertensión, medicine, 030212 general & internal medicine, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, business.industry, Consensus conference, Medicamentos cardiovasculares, [SDV] Life Sciences [q-bio], Clinical trial, Current Opinion, consensus, RDN, baroreceptor activation therapy, Cardiology and Cardiovascular Medicine, business
Abstract

Sin financiación 22.673 JCR (2019) Q1, 2/138 Cardiac & Cardiovascular Systems 5.883 SJR (2019) Q1, 4/362 Cardiology and Cardiovascular Medicine No data IDR 2019 UEM

Published
2020

23. Genome-wide association study identifies multiple new loci associated with Ewing sarcoma susceptibility

Author

Ana Patiño-García, Thomas G. P. Grunewald, David G. Cox, Lindsay M. Morton, Michelle Manning, Sandrine Grossetête-Lalami, Gaëlle Pierron, Nadège Corradini, Stephen J. Chanock, Kathleen Wyatt, Udo Kontny, Gregory T. Armstrong, Jean Michon, Sakina Zaidi, Didier Surdez, Wolfgang Hartmann, Heinrich Kovar, Olivier Delattre, Jennifer Kriebel, Nathalie Gaspar, Perrine Marec Bérard, Valérie Laurence, Casey L. Dagnall, Thomas Kirchner, Stéphanie Reynaud, Uta Dirksen, Nathaniel Rothman, Konstantin Strauch, Margaret A. Tucker, Lisa Mirabello, Smita Bhatia, Markus Metzler, Laurie Burdett, Neal D. Freedman, Rebeca Alba Rubio, Franck Tirode, Andreas E. Kulozik, Meredith Yeager, Kristine Jones, Javier Alonso, Stelly Ballet, Olivier Mirabeau, Eve Lapouble, Robert N. Hoover, Weiyin Zhou, Wendy M. Leisenring, Leslie L. Robison, Piero Picci, Javed Khan, Thomas Meitinger, Anna González-Neira, Eric Karlins, Mitchell J. Machiela, Unión Europea, TIRODE, Franck, Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Laboratory for Pediatric Sarcoma Biology [Munich, Germany], Ludwig-Maximilian-Universität München Pathologisches Institut [Germany], German Cancer Consortium [Heidelberg] (DKTK), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Unité de Génétique Somatique, Institut Curie [Paris], Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Oncologie Médicale [Institut Curie, Paris], Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, Frederick National Laboratory for Cancer Research (FNLCR), Unité de Génétique Somatique [Institut Curie, Paris], Children’s Cancer Research Institute [Vienna, Austria], Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Division of Pediatric Hematology, Oncology and Stem Cell Transplantation [Aechen, Germany], Genotyping Unit (CeGen), Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Istituto Ortopedico Rizzoli [Bologna, Italy], Unidad de Tumores Sólidos Infantiles – Unidad de Investigación Biomédica [Madrid, Spain], Instituto de Salud Carlos III [Madrid] (ISC)- Instituto de Investigación en Enfermedades Raras (IIER), Center for Applied Medical Research [Plamplona] (CIMA), Universidad de Navarra [Pamplona] (UNAV), Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Clinical Genetics Branch, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Department of Epidemiology and Cancer Control [Memphis, TN, USA], Cancer Prevention and Clinical Statistics Program [Seattle, WA, USA], Institute for Cancer Outcomes and Survivorship [Birmingham, AL, USA], University Children's Hospital of Heidelberg [Heidelberg, Germany], Research Unit of Molecular Biology [Neuherberg, Germany], Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), German Center for Diabetes Diseases [Neuherberg, Germany] (DZD), Institute of Human Genetics [Neuherberg] (IHG), Helmholtz Zentrum München = German Research Center for Environmental Health, Institute of Human Genetics [Munich, Germany], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Pediatric Oncology and Hematology [Erlangen, Germany], University Hospital Erlangen = Uniklinikum Erlangen, Gerhard-Domagk-Institute of Pathology, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Institute of Genetic Epidemiology [Neuherberg, Germany], Chair of Genetic Epidemiology [Munich, Germany] (IBE), Institute of Pathology [Munich, Germany], University Children's Hospital of Essen [Essen, Germany], This work was supported by the Intramural Research Program of the U.S. NationalCancer Institute and the Intramural Research Program of the American Cancer Society.This work was supported by grants from the Institut Curie, the Inserm, the LigueNationale Contre le Cancer (Equipe labellisée, Carte d’Identité des Tumeurs programand Recherche Epidémiologique 2009 program), the ANR-10-EQPX-03 from the AgenceNationale de la Recherche, the European PROVABES (ERA-649 NET TRANSCAN JTC2011), and ASSET (FP7-HEALTH-2010-259348) projects. This research was supportedby FP7 grant 'EURO EWING Consortium' No. 602856 and the following associations:Courir pour Mathieu, Dans les pas du Géant, Les Bagouzamanon, Enfants et Santé, M lavie avec Lisa, Lulu et les petites bouilles de lune, les Amis de Claire, l’Etoile de Martin andthe Société Française de lutte contre les Cancers et les leucémies de l’Enfant et del’adolescent. The laboratory of T. G. P. Grünewald is supported by grants from the‘Verein zur Förderung von Wissenschaft und Forschung an der Medizinischen Fakultätder LMU München (WiFoMed)’, by LMU Munich’s Institutional Strategy LMU excellentwithin the framework of the German Excellence Initiative, the ‘Mehr LEBEN für krebskranke Kinder—Bettina-Bräu-Stiftung’, the Walter Schulz Foundation, the WilhelmSander-Foundation (2016.167.1), and by the German Cancer Aid (DKH-111886 andDKH-70112257). D. Surdez is supported by SiRIC (Grant « INCa-DGOS-4654). Wethank the following clinicians for providing samples used in this study: C. Alenda, F.Almazán, D. Ansoborlo, L. Aymerich, L. Benboukbher, C. Beléndez, C. Berger, C. Bergeron, P. Biron, J.Y. Blay, E. Bompas, H. Bonnefoi, P. Boutard, B. Bui-Nguyen, D.Chauveaux, C. Calvo, A. Carboné, C. Clement, T. Contra, N. Corradini, A.S. Defachelles,V. Gandemer-Delignieres, A. Deville, A. Echevarria, J. Fayette, M. Fraga, D. Frappaz, J.L.Fuster, P. García-Miguel, J.C. Gentet, P. Kerbrat, V. Laithier, V. Laurence, P. Leblond, O.Lejars, R. López-Almaraz, B. López-Ibor, P. Lutz, J.F. Mallet, L. Mansuy, P. Marec Bérard,G. Margueritte, A. Marie Cardine, C. Melero, L. Mignot, F. Millot, O. Minckes, G.Margueritte, C. Mata, M.E. Mateos, M. Melo, C. Moscardó, M. Munzer, B. Narciso, A.Navajas, D. Orbach, C. Oudot, H. Pacquement, C. Paillard, Y. Perel, T. Philip, C. Piguet,M.I. Pintor, D. Plantaz, E. Plouvier, S. Ramirez-Del-Villar, I. Ray-Coquard, Y. Reguerre,M. Rios, P. Rohrlich, H. Rubie, A. Sastre, G. Schleiermacher, C. Schmitt, P. Schneider, L.Sierrasesumaga, C. Soler, N. Sirvent, S. Taque, E. Thebaud, A. Thyss, R. Tichit, J.J. Uriz, J.P. Vannier, F. Watelle-Pichon. This work was supported by the Instituto de SaludCarlos III (PI16CIII/00026) and the Asociación Pablo Ugarte, Fundación Sonrisa deAlex, ASION-La Hucha de Tomás, Sociedad Española de Hematología y OncologíaPediátricas. The Childhood Cancer Survivor Study is supported by the NationalCancer Institute (CA55727, G.T. Armstrong, Principal Investigator), with funding forgenotyping from the Intramural Research Program of the National Institutes ofHealth, National Cancer Institute. The KORA study was initiated and financed by theHelmholtz Zentrum München—German Research Center for Environmental Health,which is funded by the German Federal Ministry of Education and Research (BMBF) andby the State of Bavaria. Furthermore, KORA research was supported within the MunichCenter of Health Sciences (MC-Health), Ludwig-Maximilians-Universität, as part ofLMUinnovativ, Helmholtz-Zentrum München (HZM), University Hospital Erlangen [Germany], Westfälische Wilhelms-Universität Münster (WWU), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Candidate gene, Oncogene Proteins, Fusion, Medizin, General Physics and Astronomy, Genome-wide association study, Cell Cycle Proteins, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, lcsh:Science, Genetics, Multidisciplinary, Nuclear Proteins, 3. Good health, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Homeobox Protein Nkx-2.2, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Quality Control, Risk, Genotype, Science, European Continental Ancestry Group, Quantitative Trait Loci, Single-nucleotide polymorphism, Locus (genetics), [SDV.CAN]Life Sciences [q-bio]/Cancer, Sarcoma, Ewing, Biology, Quantitative trait locus, Polymorphism, Single Nucleotide, Article, White People, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Humans, Genetic Predisposition to Disease, Allele, Alleles, Cell Proliferation, Homeodomain Proteins, Proto-Oncogene Protein c-fli-1, Gene Expression Profiling, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, General Chemistry, Zebrafish Proteins, Pediatric cancer, 030104 developmental biology, Expression quantitative trait loci, lcsh:Q, RNA-Binding Protein EWS, Transcription Factors, Genome-Wide Association Study
Abstract

Ewing sarcoma (EWS) is a pediatric cancer characterized by the EWSR1-FLI1 fusion. We performed a genome-wide association study of 733 EWS cases and 1346 unaffected individuals of European ancestry. Our study replicates previously reported susceptibility loci at 1p36.22, 10q21.3 and 15q15.1, and identifies new loci at 6p25.1, 20p11.22 and 20p11.23. Effect estimates exhibit odds ratios in excess of 1.7, which is high for cancer GWAS, and striking in light of the rarity of EWS cases in familial cancer syndromes. Expression quantitative trait locus (eQTL) analyses identify candidate genes at 6p25.1 (RREB1) and 20p11.23 (KIZ). The 20p11.22 locus is near NKX2-2, a highly overexpressed gene in EWS. Interestingly, most loci reside near GGAA repeat sequences and may disrupt binding of the EWSR1-FLI1 fusion protein. The high locus to case discovery ratio from 733 EWS cases suggests a genetic architecture in which moderate risk SNPs constitute a significant fraction of risk., Ewing sarcoma (EWS) is a rare pediatric bone cancer typically involving the EWSR1-FLI1 fusion. Here the authors perform a genome-wide association study and report three new EWS risk loci that reside near GGAA repeat sequences, and identify candidate genes (RREB1 and KIZ) from eQTL analysis.

Published
2018

24. Exploration of New Contrasts, Targets, and MR Imaging and Spectroscopy Techniques for Neuromuscular Disease – A Workshop Report of Working Group 3 of the Biomedicine and Molecular Biosciences COST Action BM1304 MYO-MRI

Author

Ralph, Sinkus, Strijkers, Gustav, Araujo, Ericky C.A., Azzabou, Noura, Bendahan, David, Blamire, Andrew, Burakiewicz, Jedrek, Carlier, Pierre, Damon, Bruce, Deligianni, Xeni, Froeling, Martijn, Heerschap, Arend, Hollingsworth, Kieren, Hooijmans, Melissa, Karampinos, Dimitrios, Loudos, George, Madelin, Guillaume, Marty, Benjamin, Nagel, Armin, Nederveen, Aart, Nelissen, Jules, Santini, Francesco, Scheidegger, Olivier, Schick, Fritz, Sinclair, Christopher, Sinkus, Ralph, de Sousa, Paulo, Straub, Volker, Walter, Glenn, Kan, Hermien, Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Myology, Nuclear Magnetic Resonance Laboratory, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Newcastle University [Newcastle], Laboratoire Spécification et Vérification [Cachan] (LSV), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), University Medical Center [Utrecht], Department of Radiology, Radboud University Medical Center [Nijmegen], Technol Educ Inst Athens, Centre de résonance magnétique des systèmes biologiques (CRMSB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Service MIRCEN (MIRCEN), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University Hospital Erlangen = Uniklinikum Erlangen, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Università degli studi di Genova = University of Genoa (UniGe), EAWAG, Dept. Surface Waters Res. & Management, Swiss Federal Insitute of Aquatic Science and Technology [Dübendorf] (EAWAG), Physique des ondes pour la médecine, Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de synthèse organique (DCSO), École polytechnique (X)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Department of Neurology, ACS - Atherosclerosis & ischemic syndromes, Amsterdam Neuroscience - Brain Imaging, Biomedical Engineering and Physics, AMS - Restoration & Development, ACS - Diabetes & metabolism, Radiology and Nuclear Medicine, ACS - Heart failure & arrhythmias, Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Pierre et Marie Curie - Paris 6 (UPMC), Résonance magnétique des systèmes biologiques (RMSB), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University-Hospital Erlangen, University of Erlangen-Nuremberg, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Dipartimento di Matematica e Informatica [Perugia] (DMI), Università degli Studi di Perugia (UNIPG), Swiss Federal Institute for Environmental Science and Technology [Dübendorf] (EAWAG), Université Paris Diderot - Paris 7 (UPD7)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), University of Genoa (UNIGE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)

Subjects
0301 basic medicine, Magnetic Resonance Spectroscopy, Neurology, muscle, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV]Life Sciences [q-bio], Contrast Media, Review, Magnetic Resonance Imaging/methods, 0302 clinical medicine, Cost action, Dog Diseases, ComputingMilieux_MISCELLANEOUS, media_common, Magnetic Resonance Spectroscopy/methods, medicine.diagnostic_test, Muscles, Outcome measures, Neuromuscular Diseases, Neuromuscular disease, Magnetic Resonance Imaging, 3. Good health, Neuromuscular Diseases/diagnostic imaging, biomarker, [SDV.IB]Life Sciences [q-bio]/Bioengineering, MRI, MRS, medicine.medical_specialty, Clinical Neurology, 03 medical and health sciences, Dogs, Muscles/diagnostic imaging, Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15], medicine, media_common.cataloged_instance, Animals, Humans, Medical physics, European Union, European union, Biomedicine, Dog Diseases/diagnostic imaging, outcome measure, business.industry, Magnetic resonance imaging, medicine.disease, Clinical trial, 030104 developmental biology, myo-mri, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Contains fulltext : 203339.pdf (Publisher’s version ) (Open Access) Neuromuscular diseases are characterized by progressive muscle degeneration and muscle weakness resulting in functional disabilities. While each of these diseases is individually rare, they are common as a group, and a large majority lacks effective treatment with fully market approved drugs. Magnetic resonance imaging and spectroscopy techniques (MRI and MRS) are showing increasing promise as an outcome measure in clinical trials for these diseases. In 2013, the European Union funded the COST (co-operation in science and technology) action BM1304 called MYO-MRI (www.myo-mri.eu), with the overall aim to advance novel MRI and MRS techniques for both diagnosis and quantitative monitoring of neuromuscular diseases through sharing of expertise and data, joint development of protocols, opportunities for young researchers and creation of an online atlas of muscle MRI and MRS. In this report, the topics that were discussed in the framework of working group 3, which had the objective to: Explore new contrasts, new targets and new imaging techniques for NMD are described. The report is written by the scientists who attended the meetings and presented their data. An overview is given on the different contrasts that MRI can generate and their application, clinical needs and desired readouts, and emerging methods.

Published
2019

25. Comparative analysis of nanosystems’ effects on human endothelial and monocytic cell functions

Author

Ruth Prassl, Iwona Cicha, Maya Juenet, Harald Unterweger, Christoph Alexiou, Stefan Lyer, Jasmin Matuszak, Isabelle Texier, Cédric Chauvierre, Amr Alaarg, Didier Letourneur, Gunter Almer, Danielle Franke, Harald Mangge, Philipp Dörfler, Josbert M. Metselaar, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Otolaryngology, University Hospital Erlangen = Uniklinikum Erlangen, Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Twente, Medical University Graz, Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), RWTH University Clinic, ANR-11-LABX-0003,ARCANE,Grenoble, une chimie bio-motivée(2011), European Project: 309820,EC:FP7:NMP,FP7-NMP-2012-LARGE-6,NANOATHERO(2013), University of Twente [Netherlands], RWTH Aachen University, Biomaterials Science and Technology, University Hospital Erlangen, and Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, monocytic cell chemotaxis, Cell Survival, Surface Properties, THP-1 Cells, Cell, Cell Culture Techniques, Biomedical Engineering, Nanoparticle, Biocompatible Materials, Cell Communication, 02 engineering and technology, endothelial migration, Toxicology, Monocytes, 03 medical and health sciences, chemistry.chemical_compound, [SPI]Engineering Sciences [physics], Cell Movement, atherothrombosis, Cell Adhesion, Human Umbilical Vein Endothelial Cells, medicine, Humans, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, Cells, Cultured, Liposome, Cell chemotaxis, Chemistry, Nanoparticles, atherothrombosis, endothelial-monocyte interactions, endothelial migration, monocytic cell chemotaxis, Chemotaxis, Cell migration, Adhesion, 021001 nanoscience & nanotechnology, n/a OA procedure, 030104 developmental biology, medicine.anatomical_structure, endothelial-monocyte interactions, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Biophysics, Nanoparticles, 0210 nano-technology, Iron oxide nanoparticles
Abstract

International audience; The objective of our work was to investigate the effects of different types of nanoparticles on endothelial (HUVEC) and monocytic cell functions. We prepared and tested 14 different nanosystems comprising liposomes, lipid nanoparticles, polymer, and iron oxide nanoparticles. Some of the tested nanosystems contained targeting, therapeutic, or contrast agent(s). The effect of particles (0-400 mu g/mL) on endothelial-monocytic cell interactions in response to TNF-alpha was investigated using an arterial bifurcation model and dynamic monocyte adhesion assay. Spontaneous HUVEC migration (0-100 mu g/mL nanoparticles) and chemotaxis of monocytic cells towards MCP-1 in presence of particles (0-400 mu g/mL) were determined using a barrier assay and a modified Boyden chamber assay, respectively. Lipid nanoparticles dose-dependently reduced monocytic cell chemotaxis and adhesion to activated HUVECs. Liposomal nanoparticles had little effect on cell migration, but one formulation induced monocytic cell recruitment by HUVECs under non-uniform shear stress by about 50%. Fucoidan-coated polymer nanoparticles (25-50 mu g/mL) inhibited HUVEC migration and monocytic cell chemotaxis, and had a suppressive effect on monocytic cell recruitment under non-uniform shear stress. No significant effects of iron oxide nanoparticles on monocytic cell recruitment were observed except lauric acid and human albumin-coated particles which increased endothelial-monocytic interactions by 60-70%. Some of the iron oxide nanoparticles inhibited HUVEC migration and monocytic cell chemotaxis. These nanoparticle-induced effects are of importance for vascular cell biology and function and must be considered before the potential clinical use of some of the analyzed nanosystems in cardiovascular applications.

Published
2019
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26. Distribution of brain sodium long and short relaxation times and concentrations: a multi-echo ultra-high field 23Na MRI study

Author

Ridley, Ben, Nagel, Armin M., Bydder, Mark, Maarouf, Adil, Stellmann, Jan-Patrick, Gherib, Soraya, Verneuil, Jeremy, Viout, Patrick, Guye, Maxime, Ranjeva, Jean-Philippe, Zaaraoui, Wafaa, Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS), University-Hospital Erlangen, University of Erlangen-Nuremberg, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), ANR-15-CE19-0019,NEUROintraSOD-7T,Nouvelles stratégies pour quantifier in vivo les concentrations cérébrales intracellulaires de sodium par IRM 7T chez l'homme. Application à l'évaluation de la neurodégénérescence corticale et sous-corticale dans la sclérose en plaques(2015), ANR-11-EQPX-0001,7T AMI,Projet d'Aix-Marseille Université pour l'IRM 7T chez l'homme(2011), ANR-11-IDEX-0001,Amidex,INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE(2011), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), and University Hospital Erlangen = Uniklinikum Erlangen

Subjects
Adult, Male, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, lcsh:R, Sodium, lcsh:Medicine, Brain, Magnetic Resonance Imaging, White Matter, Article, Young Adult, Humans, lcsh:Q, Female, Gray Matter, lcsh:Science
Abstract

International audience; Sodium (23 Na) MRI proffers the possibility of novel information for neurological research but also particular challenges. Uncertainty can arise in in vivo 23 Na estimates from signal losses given the rapidity of T2* decay due to biexponential relaxation with both short (T 2 * short) and long (T 2 * long) components. We build on previous work by characterising the decay curve directly via multi-echo imaging at 7 T in 13 controls with the requisite number, distribution and range to assess the distribution of both in vivo T 2 * short and T 2 * long and in variation between grey and white matter, and subregions. By modelling the relationship between signal and reference concentration and applying it to in vivo 23 Na-MRI signal, 23 Na concentrations and apparent transverse relaxation times of different brain regions were measured for the first time. Relaxation components and concentrations differed substantially between regions of differing tissue composition, suggesting sensitivity of multi-echo 23 Na-MRI toward features of tissue composition. As such, these results raise the prospect of multi-echo 23 Na-MRI as an adjunct source of information on biochemical mechanisms in both physiological and pathophysiological states. In the physiological state, the maintenance of the transmembrane sodium (23 Na) concentration gradient (10-15 mM intracellular sodium concentration and ~140 mM extracellular sodium concentration) is a precondition for several critical cellular functions. These include the transport of ions, neurotransmitters and nutrients; regulation of osmotic and electrostatic forces on cells and macromolecules; as well as the transmission of action potentials 1-3. In the diseased state, multiple pathological pathways can lead to aberrations of these functions. Such alterations can lead to changes in intra-and extracellular concentrations due to a reduced ability to maintain resting conditions and due to conformational changes in cells themselves as well as the cellular environment in which they are embedded. Thus, 23 Na-MRI is a potential source of more direct and quantitative biochemical information than is generally possible with conventional proton (1 H) MRI 4. As such, there is substantial interest in 23 Na-MRI regarding a range of neurological conditions despite the additional complications of acquiring 23 Na-MRI signal, including stroke 5 , epilepsy 6 , tumors 7 and neurodegenerative diseases 8-12. The quadrupolar 23 Na nucleus (spin = 3/2) is subject to the influence of fluctuations in neighbouring electric fields due to net positive and non-uniform distribution of charge 3,13-15. In the presence of a magnetic field, 23 Na nuclei exhibit four discrete energy states, with three possible (single quantum, SQ) transitions (−1/2, +1/2 "cen-tral transition"; −3/2, −1/2 and 1/2, 3/2 "satellite transitions"). In highly motile environments such as plasma or cerebrospinal fluid (CSF), the correlation time (τ C) is much shorter than the Larmor period (ω 0 −1) (ω 0 • τ C ≪ 1), leading to monoexponential longitudinal (T 1) and transverse (T 2) relaxation. This is in contrast to tissue environments such as within cells and the interstitial spaces between cells where diffusion is restricted by interactions of the 23 Na cation with macromolecular anions. Such interactions modulate decay behaviour in a measurable way: the satellite transitions are subject to additional fast relaxation processes so that both T 1 and T 2 reflect

Published
2018

27. The BEACH Protein LRBA Promotes the Localization of the Heterotrimeric G-protein Golf to Olfactory Cilia

Author

Jan Kremers, Hanns Hatt, Esther Asan, Sebastian Rasche, Eva M. Neuhaus, Siv Strömberg, Andreas Gießl, Manfred W. Kilimann, Johann Helmut Brandstätter, Jenny Atorf, Denis Hervé, Stefan Kurtenbach, Ruhr University Bochum (RUB), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Uppsala Universitet [Uppsala], Department of Ophthalmology, University Hospital Erlangen, Jena University Hospital [Jena], Institut du Fer à Moulin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Department of Molecular Neurobiology [Göttingen], Max Planck Institute of Experimental Medicine [Göttingen] (MPI), Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, HAL UPMC, Gestionnaire, University Hospital Erlangen = Uniklinikum Erlangen, and Julius-Maximilians-Universität Würzburg (JMU)

Subjects
0301 basic medicine, Multidisciplinary, Vomeronasal organ, Science, Cell- och molekylärbiologi, Cilium, Protein domain, Signal transducing adaptor protein, Sensory system, Olfaction, Biology, Bioinformatics, Cell biology, LRBA, 03 medical and health sciences, 030104 developmental biology, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Heterotrimeric G protein, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Medicine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Cell and Molecular Biology
Abstract

BEACH domain proteins are involved in membrane protein traffic and human diseases, but their molecular mechanisms are not understood. The BEACH protein LRBA has been implicated in immune response and cell proliferation, and human LRBA mutations cause severe immune deficiency. Here, we report a first functional and molecular phenotype outside the immune system of LRBA-knockout mice: compromised olfaction, manifesting in reduced electro-olfactogram response amplitude, impaired food-finding efficiency, and smaller olfactory bulbs. LRBA is prominently expressed in olfactory and vomeronasal chemosensory neurons of wild-type mice. Olfactory impairment in the LRBA-KO is explained by markedly reduced concentrations (20–40% of wild-type levels) of all three subunits αolf, β1 and γ13 of the olfactory heterotrimeric G-protein, Golf, in the sensory cilia of olfactory neurons. In contrast, cilia morphology and the concentrations of many other proteins of olfactory cilia are not or only slightly affected. LRBA is also highly expressed in photoreceptor cells, another cell type with a specialized sensory cilium and heterotrimeric G-protein-based signalling; however, visual function appeared unimpaired by the LRBA-KO. To our knowledge, this is the first observation that a BEACH protein is required for the efficient subcellular localization of a lipid-anchored protein, and of a ciliary protein.

Published
2017

28. High-frequency oscillations: The state of clinical research

Author

Jerome Engel, Eishi Asano, Jean Gotman, Fabrice Bartolomei, Yvonne Höller, Joyce Y. Wu, Birgit Frauscher, Julia Jacobs, Maryse A. van 't Klooster, Katsuhiro Kobayashi, Hiroshi Otsubo, Stefan Rampp, Jan Cimbalnik, Philippe Kahane, Queen's University [Kingston, Canada], Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Okayama University Graduate School of Medicine [Okayama, Japon], St. Anne’s University Hospital [Brno], University Medical Center [Utrecht], University Hospital Erlangen = Uniklinikum Erlangen, The Hospital for sick children [Toronto] (SickKids), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), University of California [Los Angeles] (UCLA), University of California (UC), Wayne State University [Detroit], [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Université Grenoble Alpes (UGA), Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), McGill University = Université McGill [Montréal, Canada], and Bénar, Christian-G.

Subjects
0301 basic medicine, medicine.medical_specialty, Biomedical Research, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Clinical Sciences, Context (language use), [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Electroencephalography, Audiology, Neurodegenerative, Brain mapping, Article, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Clinical Research, Biological Clocks, medicine, Humans, Epilepsy surgery, Ictal, Brain Mapping, Surgical outcome, Neurology & Neurosurgery, medicine.diagnostic_test, business.industry, Neurosciences, Magnetoencephalography, Biomarker, Scalp EEG, medicine.disease, Brain Waves, Seizure, Brain Disorders, 030104 developmental biology, Clinical research, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Neurology, Neurological, Neurology (clinical), business, Sleep, Neuroscience, 030217 neurology & neurosurgery
Abstract

International audience; Modern electroencephalographic (EEG) technology contributed to the appreciation that the EEG signal outside the classical Berger frequency band contains important information. In epilepsy, research of the past decade focused particularly on interictal high-frequency oscillations (HFOs) > 80 Hz. The first large application of HFOs was in the context of epilepsy surgery. This is now followed by other applications such as assessment of epilepsy severity and monitoring of antiepileptic therapy. This article reviews the evidence on the clinical use of HFOs in epilepsy with an emphasis on the latest developments. It highlights the growing literature on the association between HFOs and postsurgical seizure outcome. A recent meta-analysis confirmed a higher resection ratio for HFOs in seizure-free versus non-seizure-free patients. Residual HFOs in the postoperative electrocorticogram were shown to predict epilepsy surgery outcome better than preoperative HFO rates. The review further discusses the different attempts to separate physiological from epileptic HFOs, as this might increase the specificity of HFOs. As an example, analysis of sleep microstructure demonstrated a different coupling between HFOs inside and outside the epileptogenic zone. Moreover, there is increasing evidence that HFOs are useful to measure disease activity and assess treatment response using noninvasive EEG and magnetoencephalography. This approach is particularly promising in children, because they show high scalp HFO rates. HFO rates in West syndrome decrease after adrenocorticotropic hormone treatment. Presence of HFOs at the time of rolandic spikes correlates with seizure frequency. The time-consuming visual assessment of HFOs, which prevented their clinical application in the past, is now overcome by validated computer-assisted algorithms. HFO research has considerably advanced over the past decade, and use of noninvasive methods will make HFOs accessible to large numbers of patients. Prospective multicenter trials are awaited to gather information over long recording periods in large patient samples.

Published
2017

29. The Nuclear Receptor Nr4a1 Acts as a Microglia Rheostat and Serves as a Therapeutic Target in Autoimmune-Driven Central Nervous System Inflammation

Author

Georg Schett, Gerhard Krönke, Tobias Rothe, Beate Winner, Daniel Metzger, Francesc Pérez-Brangulí, Hiroshi Ichinose, Maria Faas, Natacha Ipseiz, Stefanie C. Lang, University Hospital Erlangen = Uniklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Tokyo Institute of Technology [Tokyo] (TITECH), and univOAK, Archive ouverte

Subjects
Central Nervous System, 0301 basic medicine, Encephalomyelitis, Autoimmune, Experimental, Multiple Sclerosis, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.medical_treatment, Immunology, Central nervous system, Regulator, Inflammation, Biology, Nitric Oxide, Article, Mice, 03 medical and health sciences, Adenosine Triphosphate, 0302 clinical medicine, Central Nervous System Diseases, Nuclear Receptor Subfamily 4, Group A, Member 1, medicine, Animals, Humans, Immunology and Allergy, Cells, Cultured, Microglia, Multiple sclerosis, Experimental autoimmune encephalomyelitis, Neurodegenerative Diseases, Macrophage Activation, medicine.disease, Mice, Inbred C57BL, 030104 developmental biology, Cytokine, medicine.anatomical_structure, Gene Expression Regulation, nervous system, Nuclear receptor, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cytokines, medicine.symptom, Neuroscience, 030217 neurology & neurosurgery
Abstract

Microglia cells fulfill key homeostatic functions and essentially contribute to host defense within the CNS. Altered activation of microglia, in turn, has been implicated in neuroinflammatory and neurodegenerative diseases. In this study, we identify the nuclear receptor (NR) Nr4a1 as key rheostat controlling the activation threshold and polarization of microglia. In steady-state microglia, ubiquitous neuronal-derived stress signals such as ATP induced expression of this NR, which contributed to the maintenance of a resting and noninflammatory microglia phenotype. Global and microglia-specific deletion of Nr4a1 triggered the spontaneous and overwhelming activation of microglia and resulted in increased cytokine and NO production as well as in an accelerated and exacerbated form of experimental autoimmune encephalomyelitis. Ligand-induced activation of Nr4a1 accordingly ameliorated the course of this disease. Our current data thus identify Nr4a1 as regulator of microglia activation and potentially new target for the treatment of inflammatory CNS diseases such as multiple sclerosis.

Published
2017
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30. New insights into interactions between the nucleotide-binding domain of CFTR and keratin 8

Author

Premchandar, Aiswarya, Kupniewska, Anna, Bonna, Arkadiusz, Faure, Grazyna, Fraczyk, Tomasz, Roldan, Ariel, Hoffmann, Brice, Faria da Cunha, Mélanie, Herrmann, Harald, Lukacs, Gergely, Edelman, Aleksander, Dadlez, Michał, Institute of Biochemistry and Biophysics [Warsaw] (IBB), Canalopathies épithéliales: la mucoviscidose et autres maladies, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Department of Biochemistry [Cambridge], University of Cambridge [UK] (CAM), Récepteurs Canaux - Channel Receptors, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Department of Physiology [Montréal], McGill University = Université McGill [Montréal, Canada], Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Centre National de la Recherche Scientifique (CNRS), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University Hospital Erlangen = Uniklinikum Erlangen, French Cystic Fibrosis foundations Vaincre la mucoviscidose and Mucoviscidose ABCF2, MAESTRO grant from the National Science Centre, Poland, Grant number: 2014/14/A/NZ1/00306, Cystic Fibrosis Canada, Canadian Institute for Health Research, National Institute of Health, Grant number: DK075302, and GGL is a recipient of a Canada Research Chair

Subjects
intermediate filaments, NBD, LC, [SDV]Life Sciences [q-bio], SPR, Cystic Fibrosis Transmembrane Conductance Regulator, nucleotide-binding domain SPR, surface plasmon resonance cystic fibrosis, liquid chromatography MS, K8, Protein Domains, mass spectrometry NBD, HDX, liquid chromatography, [CHIM]Chemical Sciences, Humans, keratin 8, CFTR, protein structure, NBD1, mass spectrometry, keratin 8 LC, IF, hydrogen-deuterium exchange IF, Keratin-8, surface plasmon resonance cystic fibrosis CFTR keratin 8 NBD1 hydrogen-deuterium exchange mass spectrometry protein structure, Deuterium Exchange Measurement, MS, Articles, hydrogen-deuterium exchange, cystic fibrosis transmembrane conductance regulator HDX, nucleotide-binding domain, Peptides, intermediate filaments K8, hydrogen-deuterium exchange mass spectrometry
Abstract

International audience; The intermediate filament protein keratin 8 (K8) interacts with the nucleotide-binding domain 1 (NBD1) of the cystic fibrosis (CF) transmembrane regulator (CFTR) with phenylalanine 508 deletion (DF508), and this interaction hampers the biogenesis of functional DF508-CFTR and its insertion into the plasma membrane. Interruption of this interaction may constitute a new thera- peutic target for CF patients bearing the DF508 mutation. Here, we aimed to determine the binding surface between these two proteins, to facilitate the design of the interaction inhibitors. To identify the NBD1 fragments perturbed by the DF508 mutation, we used hydrogen–deuterium exchange coupled with mass spectrometry (HDX-MS) on recombinant wild-type (wt) NBD1 and DF508-NBD1 of CFTR. We then performed the same analysis in the presence of a peptide from the K8 head domain, and extended this investigation using bioinformatics procedures and surface plasmon res- onance, which revealed regions affected by the peptide binding in both wt-NBD1 and DF508-NBD1. Finally, we performed HDX-MS analysis of the NBD1 molecules and full-length K8, revealing hydrogen-bonding network changes accompanying complex formation. In conclusion, we have localized a region in the head segment of K8 that participates in its binding to NBD1. Our data also confirm the stronger binding of K8 to DF508-NBD1, which is supported by an additional binding site located in the vicinity of the DF508 mutation in NBD1.

Published
2016

31. Infections, inflammation and epilepsy

Author

Josemir W. Sander, Pierre-Marie Preux, H. Steve White, Wolfgang Löscher, Annamaria Vezzani, Robert S. Fujinami, Ingmar Blümcke, Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de l'Information Médicale et de l'Évaluation [CHU Limoges] (SIME), CHU Limoges, Laboratoire de Biostatistique et d'Informatique Médicale, Université de Limoges (UNILIM), Department of Neuropathology, University Hospital Erlangen, CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), University Hospital Erlangen = Uniklinikum Erlangen, and Grelier, Elisabeth

Subjects
0301 basic medicine, Central nervous system, Population, Epileptogenesis, Article, Pathology and Forensic Medicine, 03 medical and health sciences, Cellular and Molecular Neuroscience, Epilepsy, 0302 clinical medicine, Central Nervous System Infections, Medicine, Animals, Humans, Risk factor, education, Autoimmune encephalitis, education.field_of_study, business.industry, medicine.disease, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Immunology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), business, Meningitis, 030217 neurology & neurosurgery, Encephalitis
Abstract

International audience; Epilepsy is the tendency to have unprovoked epileptic seizures. Anything causing structural or functional derangement of brain physiology may lead to seizures, and different conditions may express themselves solely by recurrent seizures and thus be labelled "epilepsy." Worldwide, epilepsy is the most common serious neurological condition. The range of risk factors for the development of epilepsy varies with age and geographic location. Congenital, developmental and genetic conditions are mostly associated with the development of epilepsy in childhood, adolescence and early adulthood. Head trauma, infections of the central nervous system (CNS) and tumours may occur at any age and may lead to the development of epilepsy. Infections of the CNS are a major risk factor for epilepsy. The reported risk of unprovoked seizures in population-based cohorts of survivors of CNS infections from developed countries is between 6.8 and 8.3 %, and is much higher in resource-poor countries. In this review, the various viral, bacterial, fungal and parasitic infectious diseases of the CNS which result in seizures and epilepsy are discussed. The pathogenesis of epilepsy due to brain infections, as well as the role of experimental models to study mechanisms of epileptogenesis induced by infectious agents, is reviewed. The sterile (non-infectious) inflammatory response that occurs following brain insults is also discussed, as well as its overlap with inflammation due to infections, and the potential role in epileptogenesis. Furthermore, autoimmune encephalitis as a cause of seizures is reviewed. Potential strategies to prevent epilepsy resulting from brain infections and non-infectious inflammation are also considered.

Published
2016

32. T2-weighted MRI signal predicts hormone and tumor responses to somatostatin analogs in acromegaly

Author

Iulia Potorac, Patrick Petrossians, Adrian F Daly, Orsalia Alexopoulou, Sophie Borot, Mona Sahnoun-Fathallah, Frederic Castinetti, France Devuyst, Marie-Lise Jaffrain-Rea, Claire Briet, Florina Luca, Marion Lapoirie, Flavius Zoicas, Isabelle Simoneau, Alpha M Diallo, Ammar Muhammad, Fahrettin Kelestimur, Elena Nazzari, Rogelio Garcia Centeno, Susan M Webb, Marie-Laure Nunes, Vaclav Hana, Véronique Pascal-Vigneron, Irena Ilovayskaya, Farida Nasybullina, Samia Achir, Diego Ferone, Sebastian J C M M Neggers, Brigitte Delemer, Jean-Michel Petit, Christof Schöfl, Gerald Raverot, Bernard Goichot, Patrice Rodien, Bernard Corvilain, Thierry Brue, Franck Schillo, Luaba Tshibanda, Dominique Maiter, Jean-François Bonneville, Albert Beckers, Centre Hospitalier Universitaire de Liège (CHU-Liège), Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Assistance Publique - Hôpitaux de Marseille (APHM), Université libre de Bruxelles (ULB), Università degli Studi dell'Aquila () (Univaq), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg ), Centre Hospitalier Universitaire de Lyon, University Hospital Erlangen, Unité de Génétique Moléculaire Animale (UMR GMA), Université de Limoges (UNILIM)-Institut National de la Recherche Agronomique (INRA), Centre Hospitalier Universitaire de Reims (CHU Reims), Erasmus University Rotterdam, Erciyes University, University of Genoa (UNIGE), Hospital General Universitario 'Gregorio Marañón', Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), CHU Bordeaux [Bordeaux], University of Chemistry and Technology Prague (UCT Prague), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Moscow State University, Université technique de Kazan, Partenaires INRAE, Université Pierre et Marie Curie - Paris 6 (UPMC), University of Bamberg, Fonds d'Investissment pour la Recherche (FIRS) of the Centre Hospitalier Universitaire de Liege, Università degli Studi dell'Aquila = University of L'Aquila (UNIVAQ), University Hospital Erlangen = Uniklinikum Erlangen, Università degli studi di Genova = University of Genoa (UniGe), Internal Medicine, and Pediatrics

Subjects
Adenoma, Male, Cancer Research, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Treatment duration, Large population, 030209 endocrinology & metabolism, predictor, Octreotide, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Acromegaly, medicine, Humans, Insulin-Like Growth Factor I, MRI, Predictor, Somatostatin analogs, Treatment response, Female, Growth Hormone-Secreting Pituitary Adenoma, Human Growth Hormone, Middle Aged, Prognosis, Somatostatin, Treatment Outcome, Tumor Burden, Magnetic Resonance Imaging, Oncology, business.industry, treatment response, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, somatostatin analogs, Diabetes and Metabolism, Multicenter study, 030220 oncology & carcinogenesis, acromegaly, Signal intensity, business, T2 weighted, Hormone
Abstract

GH-secreting pituitary adenomas can be hypo-, iso- or hyper-intense on T2-weighted MRI sequences. We conducted the current multicenter study in a large population of patients with acromegaly to analyze the relationship between T2-weighted signal intensity on diagnostic MRI and hormonal and tumoral responses to somatostatin analogs (SSA) as primary monotherapy. Acromegaly patients receiving primary SSA for at least 3 months were included in the study. Hormonal, clinical and general MRI assessments were performed and assessed centrally. We included 120 patients with acromegaly. At diagnosis, 84, 17 and 19 tumors were T2-hypo-, iso- and hyper-intense, respectively. SSA treatment duration, cumulative and mean monthly doses were similar in the three groups. Patients with T2-hypo-intense adenomas had median SSA-induced decreases in GH and IGF-1 of 88% and 59% respectively, which were significantly greater than the decreases observed in the T2-iso- and hyper-intense groups (P P P r = 0.22), IGF-1 (P r = 0.14) and adenoma volume (P r = 0.33). The T2-weighted signal intensity of GH-secreting adenomas at diagnosis correlates with hormone reduction and tumor shrinkage in response to primary SSA treatment in acromegaly. This study supports its use as a generally available predictive tool at diagnosis that could help to guide subsequent treatment choices in acromegaly.

Published
2016

33. The second European interdisciplinary Ewing sarcoma research summit--A joint effort to deconstructing the multiple layers of a complex disease

Author

Nathan C. Sheffield, Andrei Zinovyev, Branka Radic Sarikas, Jeffrey A. Toretsky, Marc Ladanyi, Markus Metzler, Theodore Papamarkou, Guenther H. S. Richter, Enrique de Alava, Elizabeth S. Stewart, Patrick J. Grohar, Lee J. Helman, Beat W. Schäfer, Florencia Cidre-Aranaz, James F. Amatruda, Keri Schadler, Kimberly Stegmaier, Anang A. Shelat, Thomas G. P. Grunewald, Poul H. Sorensen, Paul S. Meltzer, Jaume Mora, Oscar M. Tirado, Takuro Nakamura, Joseph A. Ludwig, Olivier Delattre, Alejandro Sweet-Cordero, Uta Dirksen, Richard Moriggl, Peter J. Houghton, Claudia Rossig, Stephen L. Lessnick, Stefan Burdach, Karoly Szuhai, Elizabeth R. Lawlor, Kristiina Iljin, Franck Tirode, Wietske van der Ent, Françoise Rédini, Aykut Üren, Heinrich Kovar, Erika Brunet, Eberhard Korsching, Katia Scotlandi, Kalliopi Tsafou, Ewa Snaar-Jagalska, Unión Europea. Comisión Europea. 7 Programa Marco, Children’s Cancer Research Institute [Vienna, Austria], Department of Pediatrics [Vienna, Austria], Medizinische Universität Wien = Medical University of Vienna, Departments of Pediatrics, Molecular Biology and Internal Medicine [Dallas, TX, USA], University of Texas Southwestern Medical Center [Dallas], Structure et Instabilité des Génomes (STRING), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Children’s Cancer Research Center and Department of Pediatrics [Munich, Germany], Technical University and Comprehensive Cancer Center Munich - CCCM [Germany]-Klinikum rechts der Isar [Munich, Germany], Unidad de Tumores Sólidos Infantiles – Unidad de Investigación Biomédica [Madrid, Spain], Instituto de Salud Carlos III [Madrid] (ISC)- Instituto de Investigación en Enfermedades Raras (IIER), Laboratorio de Patología Molecular (USAL-CSIC), Centro de Investigación del Cáncer, Universitätsklinikum Münster [Munster, Germany], Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Biology [Leiden, The Netherlands], Leiden University, Center for Cancer and Cell Biology [Grand Rapids, MI, USA], Van Andel Institute [Grand Rapids]-Helen DeVos Children’s Hospital [Grand Rapids, MI, USA], Laboratory for Pediatric Sarcoma Biology [Munich, Germany], Ludwig-Maximilian-Universität München Pathologisches Institut [Germany], Center for Cancer Rearch [Bethesda, MA, USA], National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Greehey Children’s Cancer Research Institute [San Antonio, TX, USA], The University of Texas Health Science Center at Houston (UTHealth), VTT Technical Research Centre of Finland (VTT), Institute of Bioinformatics [Muenster, Germany], University of Münster, Department of Pathology and Human Oncology and Pathogenesis Program [New York, NY, USA], Memorial Sloane Kettering Cancer Center [New York], Department of Pediatrics and Department of Pathology [Ann Arbor, MI, USA], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Division of Pediatric Hematology/ Oncology/BMT [Columbus, OH, USA], Abigail Wexner Research Institute, Nationwide Children's Hospital-Nationwide Children's Hospital, Department of Sarcoma Medical Oncology [Houston, TX, USA], The University of Texas M.D. Anderson Cancer Center [Houston], Genetics Branch [Bethesda, MD, USA] (Center for Cancer Research), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Pediatric Oncology and Hematology [Erlangen, Germany], University Hospital Erlangen [Germany], Department of Pediatric Oncology [Barcelona, Spain], Hospital Sant Joan de Déu [Barcelona], Ludwig Boltzmann Institute for Cancer Research [Vienna, Austria], Institute of Animal Breeding and Genetics [Vienna, Austria] (Department for Biomedical Sciences), University of Veterinary Medicine [Vienna] (Vetmeduni), Division of Carcinogenesis [Tokyo, Japan], The Cancer Institute [Tokyo, Japan]-Japanese Foundation for Cancer Research [Tokyo, Japan], School of Mathematics and Statistics [Glasgow, UK], University of Glasgow, Research Center for Molecular Medicine of the Austrian Academy of Sciences [Vienna, Austria] (CeMM ), Austrian Academy of Sciences (OeAW), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Pediatrics Research [Houston, TX, USA], Department of Oncology and Children’s Research Center [Zurich, Switzerland], University Children’s Hospital Zurich, CRS Development of Biomolecular Therapies [Bologna, Italy] (Experimental Oncology Lab), University of Bologna-The Rizzoli Institute [Bologna, Italy], Department of Chemical Biology and Therapeutics [Memphis,TN, USA], St Jude Children's Research Hospital, Department of Molecular Oncology [British Columbia, Canada], British Columbia Cancer Research Centre [British Columbia, Canada], Department of Pediatric Oncology [Boston, MA, USA], Dana-Farber Cancer Institute [Boston], Department of Developmental Neurobiology [Memphis, TN, USA], Division of Hematology and Oncology [Stanford, CA, USA] (Department of Pediatrics), Stanford University, Department of Molecular Cell Biology [Leiden, The Netherlands], Leiden University Medical Center (LUMC), Molecular Oncology Laboratory [Barcelona, Spain] (Sarcoma Research Group), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL)-L’Hospitalet de Llobregat [Barcelona, Spain], Department of Oncology [Washington, DC, USA], Georgetown University School of Medicine [Washington, DC USA], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), The conference was supported by the European Union’s Seventh Framework Programme grants 261743 (ENCCA) and 259348 (ASSET)., European Project: 259348,EC:FP7:HEALTH,FP7-HEALTH-2010-two-stage,ASSET(2010), European Commission, Universiteit Leiden, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), University Hospital Erlangen = Uniklinikum Erlangen, Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), University of Bologna/Università di Bologna-The Rizzoli Institute [Bologna, Italy], Universiteit Leiden-Universiteit Leiden, Mines Paris - PSL (École nationale supérieure des mines de Paris), maurice, sandrine, and ASSET: Analysing and Striking the Sensitivities of Embryonal Tumours - ASSET - - EC:FP7:HEALTH2010-11-01 - 2016-04-30 - 259348 - VALID

Subjects
0301 basic medicine, Oncogene Proteins, Fusion, Complex disease, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, Bone Neoplasms, Computational biology, Disease, Review, Sarcoma, Ewing, Biology, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.CAN] Life Sciences [q-bio]/Cancer, SDG 3 - Good Health and Well-being, medicine, Humans, development, geography, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, therapy, Summit, geography.geographical_feature_category, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, epigenetics, Proto-Oncogene Protein c-fli-1, ta1182, Gene rearrangement, medicine.disease, ta3122, microenvironment, 3. Good health, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Susceptibility locus, Identification (biology), Sarcoma, RNA-Binding Protein EWS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Ewing sarcoma, Signal Transduction
Abstract

Despite multimodal treatment, long term outcome for patients with Ewing sarcoma is still poor. The second >European interdisciplinary Ewing sarcoma research summit> assembled a large group of scientific experts in the field to discuss their latest unpublished findings on the way to the identification of novel therapeutic targets and strategies. Ewing sarcoma is characterized by a quiet genome with presence of an EWSR1-ETS gene rearrangement as the only and defining genetic aberration. RNAsequencing of recently described Ewing-like sarcomas with variant translocations identified them as biologically distinct diseases. Various presentations adressed mechanisms of EWS-ETS fusion protein activities with a focus on EWS-FLI1. Data were presented shedding light on the molecular underpinnings of genetic permissiveness to this disease uncovering interaction of EWS-FLI1 with recently discovered susceptibility loci. Epigenetic context as a consequence of the interaction between the oncoprotein, cell type, developmental stage, and tissue microenvironment emerged as dominant theme in the discussion of the molecular pathogenesis and inter- and intratumor heterogeneity of Ewing sarcoma, and the difficulty to generate animal models faithfully recapitulating the human disease. The problem of preclinical development of biologically targeted therapeutics was discussed and promising perspectives were offered from the study of novel in vitro models. Finally, it was concluded that in order to facilitate rapid pre-clinical and clinical development of novel therapies in Ewing sarcoma, the community needs a platform to maintain knowledge of unpublished results, systems and models used in drug testing and to continue the open dialogue initiated at the first two Ewing sarcoma summits., The conference was supported by the European Union’s Seventh Framework Programme grants 261743(ENCCA) and 259348 (ASSET).

Published
2016

34. The first European interdisciplinary ewing sarcoma research summit

Author

Jozef Ban, Enrique de Alava, Pierre Åman, Stephen L. Lessnick, Dave N. T. Aryee, Stefan Burdach, Udo Kontny, Stephan Niedan, Jeffrey A. Toretsky, Simone Fulda, Lee J. Helman, Raphaela Schwentner, Selena Ventura, Angelika Eggert, Françoise Rédini, Antonio Llombart-Bosch, Markus Metzler, Poul H. Sorensen, Beat W. Schäfer, Heinrich Kovar, Argyro Fourtouna, Katia Scotlandi, Gunther Richter, Sue A. Burchill, Uta Dirksen, Olivier Delattre, Richard Moriggl, Elizabeth R. Lawlor, David Herrero-Martin, Javier Alonso, Martin S. Staege, Lucia T. Riedmann, Pancras C.W. Hogendoorn, Franck Tirode, Ruth Ladenstein, Claudia Rossig, Jenny Potratz, Children’s Cancer Research Institute [Vienna, Austria], Department of Pediatrics [Vienna, Austria], Medizinische Universität Wien = Medical University of Vienna, Unidad de Tumores Sólidos Infantiles – Unidad de Investigación Biomédica [Madrid, Spain], Instituto de Salud Carlos III [Madrid] (ISC)- Instituto de Investigación en Enfermedades Raras (IIER), Sahlgrenska Academy at University of Gothenburg [Göteborg], Leeds Institute of Molecular Medicine, University of Leeds, Children’s Cancer Research Center and Department of Pediatrics [Munich, Germany], Technical University and Comprehensive Cancer Center Munich - CCCM [Germany]-Klinikum rechts der Isar [Munich, Germany], University Hospital of Salamanca, Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Universitätsklinikum Münster [Munster, Germany], Goethe-University, Goethe-Universität Frankfurt am Main, Center for Cancer Rearch [Bethesda, MA, USA], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Leiden University Medical Center (LUMC), University Children's Hospital [Freiburg, Germany], Department of Pediatrics and Department of Pathology [Ann Arbor, MI, USA], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Department of Pathology [Ann Arbor, MI, USA] (Medical School), Huntsman Cancer Institute [Salt Lake City], University of Utah, University of Valencia, Pediatric Oncology and Hematology [Erlangen, Germany], University Hospital Erlangen [Germany], Ludwig Boltzmann Institute for Cancer Research [Vienna, Austria], Physiopathologie de la résorption osseuse et thérapie des tumeurs osseuses primitives, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Oncology and Children’s Research Center [Zurich, Switzerland], University Children’s Hospital Zurich, CRS Development of Biomolecular Therapies [Bologna, Italy] (Experimental Oncology Lab), University of Bologna-The Rizzoli Institute [Bologna, Italy], Department of Molecular Oncology [British Columbia, Canada], British Columbia Cancer Research Centre [British Columbia, Canada], Children's Cancer Research Center [Halle, Germany], Georgetown Lombardi Comprehensive Cancer Center, University Children's Hospital of Essen, Klinikum rechts der Isar [Munich, Germany]-Technical University and Comprehensive Cancer Center Munich - CCCM [Germany], TIRODE, Franck, Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), University Hospital Erlangen = Uniklinikum Erlangen, University of Bologna/Università di Bologna-The Rizzoli Institute [Bologna, Italy], and Widemann, BC

Subjects
Epigenomics, Cancer Research, Alternative medicine, Medizin, ComputingMilieux_LEGALASPECTSOFCOMPUTING, Review Article, Bioinformatics, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, drug screen, 0302 clinical medicine, Drug screen, Cancer genomics, signalling, Sarcomagenesis, 0303 health sciences, sarcomagenesis, Summit, geography.geographical_feature_category, Opinion leadership, Genomics, Laboratory results, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, animal models, 3. Good health, Animal models, Metastatic Ewing Sarcoma, Oncology, 030220 oncology & carcinogenesis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Epigenetics, Sarcoma, Immunotherapy, Prioritization, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, genomics, 030304 developmental biology, Medical education, geography, epigenetics, business.industry, biomarkers, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, Clinical trial, prognosis, business, Biomarkers, Ewing sarcoma
Abstract

This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License.-- et al., The European Network for Cancer Research in Children and Adolescents (ENCCA) provides an interaction platform for stakeholders in research and care of children with cancer. Among ENCCA objectives is the establishment of biology-based prioritization mechanisms for the selection of innovative targets, drugs, and prognostic markers for validation in clinical trials. Specifically for sarcomas, there is a burning need for novel treatment options, since current chemotherapeutic treatment protocols have met their limits. This is most obvious for metastatic Ewing sarcoma (ES), where long term survival rates are still below 20%. Despite significant progress in our understanding of ES biology, clinical translation of promising laboratory results has not yet taken place due to fragmentation of research and lack of an institutionalized discussion forum. To fill this gap, ENCCA assembled 30 European expert scientists and five North American opinion leaders in December 2011 to exchange thoughts and discuss the state of the art in ES research and latest results from the bench, and to propose biological studies and novel promising therapeutics for the upcoming European EWING2008 and EWING2012 clinical trials.

Published
2012

35. The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission

Author

Blümcke, Ingmar, Thom, Maria, Aronica, Eleonora, Armstrong, Dawna, Vinters, Harry, Palmini, Andre, Jacques, Thomas, Avanzini, Giuliano, Barkovich, James, Battaglia, Giorgio, Becker, Albert, Cepeda, Carlos, Cendes, Fernando, Colombo, Nadia, Peter, Crino, Cross, Helen, Delalande, Olivier, Dubeau, François, Duncan, John, Guerrini, Renzo, Kahane, Philippe, Mathern, Gary, Najm, Imad, Ozkara, Ciğdem, Raybaud, Charles, Represa, Alfonso, Roper, Steven, Salamon, Noriko, Schulze-Bonhage, Andreas, Tassi, Laura, Vezzani, Annamaria, Spreafico, Roberto, Department of Neuropathology, University Hospital Erlangen = Uniklinikum Erlangen, University College of London [London] (UCL)-Institute of Neurology, Department of (Neuro)Pathology, Academic Medisch Centrum, University of Amsterdam [Amsterdam] (UvA)-Stichting Epilepsie Instellingen Nederland (SEIN), Texas Children's Hospital [Houston, USA], Departments of Pathology and Laboratory Medicine (Neuropathology) and Neurology, UCLA Medical Center-David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Servico de Neurologia, Universidade Catolica do Rio Grande do Sul-Hospital Sao Lucas da Pontifica, UCL-Institute of Child Health (ICH), Great Ormond Street Hospital for Children [London] (GOSH)-Institute of Child Health, Department of Epilepsy Clinic and Experimental Neurophysiology, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Department of Neuroradiology, University of California [San Francisco] (UC San Francisco), Molecular Neuroanatomy and Pathogenesis Unit, University of Bonn Medical Center, Intellectual and Developmental Disabilities Research Center (IDDRC), UCLA Medical Center-Semel Institute, Department of Neurology, Universidade Estadual de Campinas = University of Campinas (UNICAMP), Ospedale Niguardia, PENN Epilepsy Center, University of Pennsylvania, The Prince of Wales's Chair of Childhood Epilepsy, Great Ormond Street Hospital for Children [London] (GOSH)-UCL-Institute of Child Health-National Centre for Young People with Epilepsy, Service de Neurochirurgie Pediatrique, Fondation Ophtalmologique Rotschild, Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], Department of Clinical and Experimental Epilepsy, Pediatric Neurology Unit and Laboratories, Università degli Studi di Firenze = University of Florence (UniFI)-Children's Hospital A. Meyer, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de neurologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Departments of Neurosurgery, Psychiatry and Behavioral Science, David Geffen School of Medicine [Los Angeles], Neurological Institute, Cleveland Clinic, Cerrahpasa Medical Faculty-Istanbul University, Division of Neuroradiology, Hospital for Sick Children-Department of Diagnostic Imaging, Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Neurosurgery, University of Florida [Gainesville] (UF), Departement of Radiology, Epilepsy Centre, University Hospital Freiburg, Centre « Claudio-Munari » pour la chirurgie de l'épilepsie et du Parkinson, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Department of Neuroscience, Mario Negri Institute for Pharmacological Research - Milan, Janssen- Cilag, UCB, GSK, NIH R01 NS38992, ANS - Amsterdam Neuroscience, APH - Amsterdam Public Health, Neurology, Pathology, University Hospital Erlangen, University of Amsterdam [Amsterdam] (UvA)-Stichting Epilepsie Instellingen Nederland, University of California-University of California-University of California [Los Angeles] (UCLA), University of California-University of California, University of California [San Francisco] (UCSF), University of Campinas [Campinas] (UNICAMP), University of Pennsylvania [Philadelphia], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)-Children's Hospital A. Meyer, Istanbul University -Cerrahpasa Medical Faculty, Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), and Deransart, Colin

Subjects
Cerebral Cortex, clinicopathologic spectrum, MESH: Humans, Advisory Committees, MESH: Societies, Medical, Global Health, Article, MESH: Cerebral Cortex, Malformations of Cortical Development, MESH: Malformations of Cortical Development, epilepsy, Humans, MESH: Advisory Committees, cortical dysplasia, Societies, Medical, MESH: World Health
Abstract

Focal cortical dysplasias (FCDs) are localized regions of malformed cerebral cortex and are very frequently associated with epilepsy in both children and adults. A broad spectrum of histopathology has been included in the diagnosis of FCD. Characteristic findings include aberrant radial or tangential lamination of the neocortex (FCD Type I) and cytological abnormalities (FCD Type II). An ILAE task force has re-evaluated available data and proposes a clinico-pathologic classification system of FCDs. The major change since a prior classification represents the introduction of FCD Type III, which occurs in combination with Hippocampal Sclerosis (FCD Type IIIa), or with epilepsy-associated tumors (FCD Type IIIb). FCD Type IIIc is found adjacent to vascular malformations, whereas FCD Type IIId can be diagnosed in association with epileptogenic lesions acquired in early life (i.e., traumatic injury, ischemic injury or encephalitis). Hence, FCD Type I will now refer to isolated lesions, which present either as radial (FCD Type Ia) or tangential (FCD Type Ib) dyslamination of the neocortex, microscopically identified in one or multiple lobes. FCD Type II is an isolated lesion characterized by cortical dyslamination and dysmorphic neurons without (Type IIa) or with balloon cells (Type IIb). Architectural abnormalities adjacent to or within gross malformations of cortical development are frequently observed and not distinguished as a specific FCD variant. This three-tiered classification system will help to better characterize specific clinico-pathological entities and is an important basis to further explore imaging, electro-clinical features, and postsurgical seizure control as well as underlying molecular pathomechanisms.

Published
2011

36. Approaches to Legal Rationality

Author

Shahid Rahman, Alexandre Thiercelin, Patrice Canivez, Dov M. Gabbay, Savoirs, Textes, Langage (STL) - UMR 8163 (STL), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'informatique Fondamentale de Marseille - UMR 6166 (LIF), Université de la Méditerranée - Aix-Marseille 2-Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), University Hospital Erlangen = Uniklinikum Erlangen, ADA-MESHS-STL, ANR-11-FRAL-0003,Jurilog,Théorie du Droit et Logique(2011), and University Hospital Erlangen

Subjects
Logic, ComputingMilieux_LEGALASPECTSOFCOMPUTING, Rationality, Civil Law, 0102 computer and information sciences, 0603 philosophy, ethics and religion, 01 natural sciences, Argumentation theory, Legal realism, [SHS.DROIT]Humanities and Social Sciences/Law, Legal formalism, ComputingMilieux_MISCELLANEOUS, Jurisprudence, Philosophy, epistemology, [SHS.PHIL]Humanities and Social Sciences/Philosophy, 06 humanities and the arts, 16. Peace & justice, Epistemology, Philosophy of logic, 010201 computation theory & mathematics, 060302 philosophy, Philosophy of law, Roman Law, Empirical legal studies, Law
Abstract

Legal theory, political sciences, sociology, philosophy, logic, artificial intelligence: there are many approaches to legal argumentation. Each of them provides specific insights into highly complex phenomena. Different disciplines, but also different traditions in disciplines (e.g. analytical and continental traditions in philosophy) find here a rare occasion to meet. The present book contains contributions, both historical and thematic, from leading researchers in several of the most important approaches to legal rationality. One of the main issues is the relation between logic and law: the way logic is actually used in law, but also the way logic can make law explicit. An outstanding group of philosophers, logicians and jurists try to meet this issue. The book is more than a collection of papers. However different their respective conceptual tools may be, the authors share a common conception: legal argumentation is a specific argumentation context.

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