EPMA-World Congress 2015: Bonn, Germany. 3-5 September 2015

Table of contents A1 Predictive and prognostic biomarker panel for targeted application of radioembolisation improving individual outcomes in hepatocellular carcinoma Jella-Andrea Abraham, Olga Golubnitschaja A2 Integrated market access approach amplifying value of “Rx-CDx” Ildar Akhmetov A3 Disaster response: an opportunity to improve global healthcare Russell J. Andrews, Leonidas Quintana A4 USA PPPM: proscriptive, profligate, profiteering medicine-good for 1 % wealthy, not for 99 % unhealthy Russell J. Andrews A5 The role of IDO in a murine model of gingivitis: predictive and therapeutic potentials Babak Baban, Jun Yao Liu, Xu Qin, Tailing Wang, Mahmood S. Mozaffari A6 Specific diets for personalised treatment of diabetes type 2 Viktoriia V. Bati, Tamara V. Meleshko, Olga B. Levchuk, Nadiya V. Boyko A7 Towards personalized physiotherapeutic approach Joanna Bauer, Ewa Boerner, Halina Podbielska A8 Cells, animal, SHIME and in silico models for detection and verification of specific biomarkers of non-communicable chronic diseases Alojz Bomba, Viktor O. Petrov, Volodymyr G. Drobnych, Rostyslav V. Bubnov, Oksana M. Bykova, Nadiya V. Boyko A9 INTERACT-chronic care model: Self-treatment by patients with decision support e-Health solution Hans-Peter Brunner-La Rocca, Lutz Fleischhacker, Olga Golubnitschaja, Frank Heemskerk, Thomas Helms, Tiny Jaarsma, Judita Kinkorova, Jan Ramaekers, Peter Ruff, Ivana Schnur, Emilio Vanoli, Jose Verdu A10 PPPM in cardiovascular medicine in 2015 Hans-Peter Brunner-La Rocca A11 Magnetic resonance imaging of nanoparticles in mice, potential for theranostic and contrast media development – pilot results Rostyslav V. Bubnov, Sergiy A. Grabovetskyi, Olena M. Mykhalchenko, Natalia O. Tymoshok, Oleksandr B. Shcherbakov, Igor P. Semeniv, Mykola Y. Spivak A12 Ultrasound diagnosis for diabetic neuropathy - comparative study Rostyslav V. Bubnov, Tetyana V. Ostapenko A13 Ultrasound for stratification patients with diabetic foot ulcers for prevention and personalized treatment - pilot results Rostyslav V. Bubnov, Nazarii M. Kobyliak, Nadiya M. Zholobak, Mykola Ya. Spivak A14 Project ImaGenX – designing and executing a questionnaire on environment and lifestyle risk of breast cancer John Paul Cauchi A15 Genomics – a new structural brand of predictive, preventive and personalized medicine or the new driver as well? Dmitrii Cherepakhin, Marina Bakay, Artem Borovikov, Sergey Suchkov A16 Survey of questionnaires for evaluation of the quality of life in various medical fields Barbara Cieślik, Agnieszka Migasiewicz, Maria-Luiza Podbielska, Markus Pelleter, Agnieszka Giemza, Halina Podbielska A17 Personalized molecular treatment for muscular dystrophies Sebahattin Cirak A18 Secondary mutations in circulating tumour DNA for acquired drug resistance in patients with advanced ALK + NSCLC Marzia Del Re, Paola Bordi, Valentina Citi, Marta Palombi, Carmine Pinto, Marcello Tiseo, Romano Danesi A19 Recombinant species-specific FcεRI alpha proteins for diagnosis of IgE-mediated allergies in dogs, cats and horses Lukas Einhorn, Judit Fazekas, Martina Muhr, Alexandra Schoos, Lucia Panakova, Ina Herrmann, Krisztina Manzano-Szalai, Kumiko Oida, Edda Fiebiger, Josef Singer, Erika Jensen-Jarolim A20 Global methodology for developmental neurotoxicity testing in humans and animals early and chronically exposed to chemical contaminants Arpiné A. Elnar, Nadia Ouamara, Nadiya Boyko, Xavier Coumoul, Jean-Philippe Antignac, Bruno Le Bizec, Gauthier Eppe, Jenny Renaut, Torsten Bonn, Cédric Guignard, Margherita Ferrante, Maria Liusa Chiusano, Salvatore Cuzzocrea, Gerard O'Keeffe, John Cryan, Michelle Bisson, Amina Barakat, Ihsane Hmamouchi, Nasser Zawia, Anumantha Kanthasamy, Glen E. Kisby, Rui Alves, Oscar Villacañas Pérez, Kim Burgard, Peter Spencer, Norbert Bomba, Martin Haranta, Nina Zaitseva, Irina May, Stéphanie Grojean, Mathilde Body-Malapel, Florencia Harari, Raul Harari, Kristina Yeghiazaryan, Olga Golubnitschaja, Vittorio Calabrese, Christophe Nemos, Rachid Soulimani A21 Mental indicators at young people with attributes hypertension and pre-hypertension Maria E. Evsevyeva, Elena A. Mishenko, Zurida V. Kumukova, Evgeniy V. Chudnovsky, Tatyana A. Smirnova A22 On the approaches to the early diagnosis of stress-induced hypertension in young employees of State law enforcement agencies Maria E. Evsevyeva, Ludmila V. Ivanova, Michail V. Eremin, Maria V. Rostovtseva A23 Сentral aortic pressure and indexes of augmentation in young persons in view of risk factors Maria E. Evsevyeva, Michail V. Eremin, Vladimir I. Koshel, Oksana V. Sergeeva, Nadesgda M. Konovalova A24 Breast cancer prediction and prevention: Are reliable biomarkers in horizon? Shantanu Girotra, Olga Golubnitschaja A25 Flammer Syndrome and potential formation of pre-metastatic niches: A multi-centred study on phenotyping, patient stratification, prediction and potential prevention of aggressive breast cancer and metastatic disease Olga Golubnitschaja, Manuel Debald, Walther Kuhn, Kristina Yeghiazaryan, Rostyslav V. Bubnov, Vadym M. Goncharenko, Ulyana Lushchyk, Godfrey Grech, Katarzyna Konieczka A26 Innovative tools for prenatal diagnostics and monitoring: improving individual pregnancy outcomes and health-economy in EU Olga Golubnitschaja, Jan Jaap Erwich, Vincenzo Costigliola, Kristina Yeghiazaryan, Ulrich Gembruch A27 Immunohistochemical assessment of APUD cells in endometriosis Vadym M. Goncharenko, Vasyl O. Beniuk, Olga V. Kalenska, Rostyslav V. Bubnov A28 Updating personalized management algorithm of endometrial hyperplasia in pre-menopause women Vadym M. Goncharenko, Vasyl O. Beniuk, Rostyslav V. Bubnov, Olga Melnychuk A29 The personified treatment approach of polimorbid patients with periodontal inflammatory diseases Irina A. Gorbacheva, Lyudmila Y. Orekhova, Vadim V. Tachalov A30 Ukrainian experience in hybrid war – the challenge to update algorithms for personalized care and early prevention of different military injuries Olena I. Grechanyk, Rizvan Ya. Abdullaiev, Rostyslav V. Bubnov A31 Tear fluid biomarkers: a comparison of tear fluid sampling and storage protocols Suzanne Hagan, Eilidh Martin, Ian Pearce, Katherine Oliver A32 The correlation of dietary habits with gingival problems during menstruation Cenk Haytac, Fariz Salimov, Servin Yoksul, Anatoly A. Kunin, Natalia S. Moiseeva A33 Genomic medicine in a contemporary Spanish population of prostate cancer: our experience Bernardo Herrera-Imbroda, Sergio del Río-González, Maria Fernanda Lara, Antonia Angulo, Francisco Javier Machuca Santa-Cruz A34 Challenges, opportunities and collaborations for personalized medicine applicability in uro-oncological disease Bernardo Herrera-Imbroda, Sergio del Río-González, Maria Fernanda Lara A35 Metabolic hallmarks of cancer as targets for a personalized therapy John Ionescu A36 Influence of genetic polymorphism as a predictor of the development of periodontal disease in patients with gastric ulcer and 12 duodenal ulcer Alfiya Z. Isamulaeva, Anatoly A. Kunin, Shamil Sh. Magomedov, Aida I. Isamulaeva A37 Challenges in diabetic macular edema Tatjana Josifova A38 Overview of the EPMA strategies in laboratory medicine relevant for PPPM Marko Kapalla, Juraj Kubáň, Olga Golubnitschaja, Vincenzo Costigliola A39 EPMA initiative for effective organization of medical travel: European concepts and criteria Vincenzo Costigliola, Marko Kapalla, Juraj Kubáň, Olga Golubnitschaja A40 Design and innovation in e-textiles: implications for PPPM Anthony Kent, Tom Fisher, Tilak Dias A41 Biobank in Pilsen as a member of national node BBMRI_CZ Judita Kinkorová, Ondřej Topolčan A42 Big data in personalized medicine: hype and hope Matthias Kohl A43 The 3P approach as the platform of the European Dentistry Department (DPPPD) Anatoly A. Kunin, Natalia S. Moiseeva A44 The endometrium cytokine patterns for predictive diagnosis of proliferation severity and cancer prevention Andrii I. Kurchenko, Vasyl A. Beniuk, Vadym M. Goncharenko, Rostyslav V. Bubnov, Nadiya V. Boyko, Andriy M. Strokan A45 A monocyte-based in-vitro system for testing individual responses to the implanted material: future for personalized implant construction Julia Kzhyshkowska, Alexandru Gudima, Ksenia S. Stankevich, Victor D. Filimonov4, Harald Klüter, Evgeniya M. Mamontova, Sergei I. Tverdokhlebov A46 Prediction and prevention of adverse health effects by meteorological factors: Biomarker patterns and creation of a device for self-monitoring and integrated care Ulyana B. Lushchyk, Viktor V. Novytskyy, Igor P. Babii, Nadiya G. Lushchyk, Lyudmyla S. Riabets, Ivanna I. Legka A47 Targeting "disease signatures" towards personalized healthcare Mira Marcus-Kalish, Alexis Mitelpunkt, Tal Galili, Neta Shachar, Yoav Benjamini A48 Influence of the skin imperfection on the personal quality of life and possible tools for objective diagnosis Agnieszka Migasiewicz, Markus Pelleter, Joanna Bauer, Ewelina Dereń, Halina Podbielska A49 The new direction in caries prevention based on the ultrastructure of dental hard tissues and filling materials Natalia S. Moiseeva, Anatoly A. Kunin, Dmitry A. Kunin A50 The use of LED radiation in prevention of dental diseases Natalia S. Moiseeva, Yury A. Ippolitov, Dmitry A. Kunin, Alexei N. Morozov, Natalia V. Chirkova, Nakhid T. Aliev A51 Status of endothelial progenitor cells in diabetic nephropathy: predictive and preventive potentials Mahmood S. Mozaffari, Jun Yao Liu, Babak Baban A52 The status of glucocorticoid-induced leucine zipper protein in salivary gland in Sjögren’s syndrome: predictive and personalized treatment potentials Mahmood S. Mozaffari, Jun Yao Liu, Rafik Abdelsayed, Xing-Ming Shi, Babak Baban A53 Maximal aerobic capacity - important quality marker of health Jaroslav Novák, Milan Štork, Václav Zeman A54 The EMPOWER project: laboratory medicine and Horizon 2020 Wytze P. Oosterhuis, Elvar Theodorsson A55 Personality profile manifestations in patient’s attitude to oral care and adherence to doctor’s prescriptions Lyudmila Y. Orekhova, Tatyana V. Kudryavtseva, Elena R. Isaeva, Vadim V. Tachalov, Ekaterina S. Loboda A56 Results of an European survey on personalized medicine addressed to directions of laboratory medicine Mario Pazzagli, Francesca Malentacchi, Irene Mancini, Ivan Brandslund, Pieter Vermeersch, Matthias Schwab, Janja Marc, Ron H.N. van Schaik, Gerard Siest, Elvar Theodorsson, Chiara Di Resta A57 MCI or early dementia predictive speech based diagnosis techniques Matus Pleva, Jozef Juhar A58 Personalized speech based mobile application for eHealth Matus Pleva, Jozef Juhar A59 Circulating tumor cell-free DNA as the biomarker in the management of cancer patients Jiří Polívka jr., Filip Janků, Martin Pešta, Jan Doležal, Milena Králíčková, Jiří Polívka A60 Complex stroke care – educational programme in Stroke Centre University Hospital Plzen Jiří Polívka, Alena Lukešová, Nina Müllerová, Petr Ševčík, Vladimír Rohan A61 Sleep apnea and sleep fragmentation contribute to brain aging Kneginja Richter, Lence Miloseva, Günter Niklewski A62 Personalised approach for sleep disturbances in shift workers Kneginja Richter, Jens Acker, Guenter Niklewski A63 Medical travel and innovative PPPM clusters: new concept of integration Olga Safonicheva, Vincenzo Costigliola A64 Medical travel and women health Olga Safonicheva A65 Continuity of generations in the training of specialists in the field of reconstructive microsurgery Maxim Sautin, Janna Sinelnikova, Sergey Suchkov A66 Telemonitoring of stroke patients – empirical evidence of individual risk management results from an observational study in Germany Songül Secer, Stephan von Bandemer A67 Women’s increasing breast cancer risk with n-6 fatty acid intake explained by estrogen-fatty acid interactive effect on DNA damage: implications for gender-specific nutrition within personalized medicine Niva Shapira A68 Cytobacterioscopy of the gingival crevicular fluid as a method for preventive diagnosis of periodontal diseases Aleksandr Shcherbakov, Anatoly A. Kunin, Natalia S. Moiseeva A69 Use of specially treated composites in dentistry to avoid violations of aesthetics Bogdan R. Shumilovich, Zhanna Lipkind, Yulia Vorobieva, Dmitry A. Kunin, Anastasiia V. Sudareva A70 National eHealth system – platform for preventive, predictive and personalized diabetes care Ivica Smokovski, Tatjana Milenkovic A72 The common energy levels of Prof. Szent-Györgyi, the intrinsic chemistry of melanin, and the muscle physiopathology. Implications in the context of Preventive, Predictive, and Personalized Medicine Arturo Solís-Herrera, María del Carmen Arias-Esparza, Sergey Suchkov A73 Plurality and individuality of hepatocellular carcinoma: PPPM perspectives Krishna Chander Sridhar, Olga Golubnitschaja A74 Strategic aspects of higher medical education reforms to secure newer educational platforms for getting biopharma professionals matures Maria Studneva, Sihong Song, James Creeden, Мark Мandrik, Sergey Suchkov A75 Overview of the strategies and activities of the European Federation of Clinical Chemistry and Laboratory Medicine, (EFLM) Elvar Theodorsson, EFLM A76 New spectroscopic techniques for point of care label free diagnostics Syed A. M. Tofail A77 Tumor markers for personalized medicine and oncology - the role of Laboratory Medicine Ondřej Topolčan, Judita Kinkorová, Ondřej Fiala, Marie Karlíková, Šárka Svobodová, Radek Kučera, Radka Fuchsová, Vladislav Třeška, Václav Šimánek, Ladislav Pecen, Jan Šoupal, Štěpán Svačina2 A78 Modern medical terminology (MMT) as a driver of the global educational reforms Evgeniya Tretyak, Maria Studneva, Sergey Suchkov A79 Juvenile hypertension; the relevance of novel predictive, preventive and personalized assessment of its determinants Francesca M. Trovato, G. Fabio Martines, Daniela Brischetto, Daniela Catalano, Giuseppe Musumeci, Guglielmo M. Trovato A80 Proteomarkers Biotech George Th. Tsangaris, Athanasios K. Anagnostopoulos A81 Proteomics and mass spectrometry based non-invasive prenatal testing of fetal health and pregnancy complications George Th. Tsangaris, Athanasios K. Anagnostopoulos A82 Integrated Ecosystem for an Integrated Care model for Heart Failure (HF) patients including related comorbidities (ZENITH) José Verdú, German Gutiérrez, Jordi Rovira, Marta Martinez, Lutz Fleischhacker, Donna Green, Arthur Garson, Elena Tamburini, Stefano Cuomo, Juan Martinez-Leon, Teresa Abrisqueta, Hans-Peter Brunner-La Rocca, Tiny Jaarsma, Teresa Arredondo, Cecilia Vera, Giuseppe Fico, Olga Golubnitschaja, Fernando Arribas, Martina Onderco, Isabel Vara, on behalf of ZENITH consortium A83 Predictive, preventive and personalized medicine in diabetes onset and complication (MOSAIC project) José Verdú, Francesco Sambo, Barbara Di Camillo, Claudio Cobelli, Andrea Facchinetti, Giuseppe Fico, Riccardo Bellazzi, Lucia Sacchi, Arianna Dagliati, Daniele Segnani, Valentina Tibollo, Manuel Ottaviano, Rafael Gabriel, Leif Groop, Jacqueline Postma, Antonio Martinez, Liisa Hakaste, Tiinamaija Tuomi, Konstantia Zarkogianni, on behalf of MOSAIC consortium A84 Possibilities for personalized therapy of diabetes using in vitro screening of insulin and oral hypoglycemic agents Igor Volchek, Nina Pototskaya, Andrey Petrov A85 The innovative technology for personalized therapy of human diseases based on in vitro drug screening Igor Volchek, Nadezhda Pototskaya, Andrey Petrov A86 Bone destruction and temporomandibular joint: predictive markers, pathogenetic aspects and quality of life Ülle Voog-Oras, Oksana Jagur, Edvitar Leibur, Priit Niibo, Triin Jagomägi, Minh Son Nguyen, Chris Pruunsild, Dagmar Piikov, Mare Saag A87 Sub-optimal health management – global vision for concepts in medical travel Wei Wang A88 Sub-optimal health management: synergic PPPM-TCAM approach Wei Wang A89 Innovative technologies for minimal invasive diagnostics Andreas Weinhäusel, Walter Pulverer, Matthias Wielscher, Manuela Hofner, Christa Noehammer, Regina Soldo, Peter Hettegger, Istvan Gyurjan, Ronald Kulovics, Silvia Schönthaler, Gabriel Beikircher, Albert Kriegner, Stephan Pabinger, Klemens Vierlinger A90 Rare disease diobanks for personalized medicine Ayşe Yüzbaşıoğlu, Meral Özgüç, Member of EuroBioBank - European Network of DNA, Cell and Tissue Banks for Rare Disease

Relation structure-fonction de FUS, une protéine de liaison à l'ARN, dans la réparation de l'ADN

Cells have evolved complex repair mechanisms to maintain the integrity of their genomes, and one of these mechanisms involves the PARP-1 enzyme and the synthesis of poly(ADP-ribose) (PAR). PARP-1 is recruited to the sites of DNA damage, where it synthesizes long negatively charged PAR chains attached to itself and other acceptor proteins. The PAR chains then act as a scaffold for the recruitment of other proteins, such as DNA repair factors, which are required for proper DNA repair.In recent studies, various RNA-binding proteins (RBPs) have been found to play a role in DNA repair. When considering DNA repair mechanisms that are dependent on PARP-1 activation, it appears that members of the FET family, particularly FUS, play a central role. FUS is recruited to DNA damage sites after laser beam exposure, and this recruitment depends on PARP-1 activity. FUS was identified in mass-spectrometry analyses of PARylated proteins following genotoxic stress and was shown to interact directly with PAR. In addition, FUS was shown to form the compartments through the interactions occurring between its low-complexity domains. Particularly, the formation of such compartments was observed at DNA damage sites following PARP-1 activation.The aim of this study is to investigate the biological functions of FUS in DNA repair mechanisms related to PARP-1 activation. FUS is known to participate in transcription by interacting with the C-terminal domain of RNA pol II and binding to nascent mRNA. Given that DNA damages often occur in open, transcriptionally-active chromatin, FUS is located in close proximity to DNA damage sites and can be rapidly directed to them. In this regard, the first question addressed in this study was the link between transcription and DNA repair in the context of FUS functions in the nucleus. Secondly, we asked whether FUS's function in PARP-1-dependent DNA repair is based on its ability to bind PAR. While other RNA-binding proteins can also bind to PAR through electrostatic interactions, FUS has a unique propensity for binding to and being PARylated. Therefore, understanding the structural characteristics that make FUS unique among other RNA-binding proteins and the nature of FUS-PAR interactions can help shed light on its role in DNA repair.In this study, we utilized a structural approach to demonstrate the specific interaction of the single RRM domain of FUS with protein-free PAR. Unlike other RNA-binding proteins, FET protein RRMs lack several aromatic residues that usually interact with RNA bases. Our NMR spectroscopy analysis shows that this provides a basis for the similar interaction of FUS RRM with RNA and PAR. Furthermore, we investigated whether FUS plays a role in controlling the overall level of PAR in the nucleus of HeLa cells following oxidative stress and transcription arrest. Our results indicate that FUS can significantly increase the level of PARylation in cells exposed to mild concentrations of hydrogen peroxide, an oxidative stress agent known to strongly activate PARP-1. This finding is consistent with the link between transcription and DNA repair, as stalling transcription significantly increases the capacity of FUS to increase the PAR level in HeLa cells exposed to hydrogen peroxide. Additionally, we identified certain residues located in the RRM of FUS, previously identified as PARylated, that control the autoPARylation of PARP-1 in vitro and the level of PARP-1 activity in cells. Overall, these results provide a basis for understanding the specific role of FUS in PARP-1-related DNA repair mechanisms.Les cellules ont développé des mécanismes de réparation complexes pour maintenir l'intégrité de leurs génomes, et l'un de ces mécanismes implique l'enzyme PARP-1 et la synthèse de poly(ADP-ribose) (PAR). PARP-1 est recruté sur les sites de dommages à l'ADN, où il synthétise de longues chaînes PAR chargées négativement attachées à lui-même et à d'autres protéines. Les chaînes PAR agissent alors comme un échafaudage pour le recrutement d'autres protéines, qui sont nécessaires à une réparation correcte de l'ADN.Dans des études récentes, diverses protéines de liaison à l'ARN se sont avérées jouer un rôle dans la réparation de l'ADN. Lorsque l'on considère les mécanismes de réparation de l'ADN qui dépendent de l'activation de PARP-1, il semble que les membres de la famille FET, en particulier FUS, jouent un rôle central. FUS est recruté sur les sites de dommages à l'ADN après exposition au faisceau laser. Il a été identifié dans des analyses par spectrométrie de masse de protéines PARylées suite à un stress génotoxique et il a été démontré qu'il interagit directement avec le PAR. De plus, FUS a été démontré comme formant des compartiments grâce à des interactions entre ses domaines de faible complexité, comme observé au niveau des sites de dommages à l'ADN suite à l'activation de PARP-1.Le but de cette étude est d'étudier les fonctions biologiques de FUS dans les mécanismes de réparation de l'ADN liés à l'activation de PARP-1. FUS est connu pour participer à la transcription en interagissant avec l'ARN Pol II et en se liant à l'ARNm naissant. Étant donné que les dommages à l'ADN se produisent souvent dans la chromatine ouverte et transcriptionnellement active, FUS est situé à proximité des sites de dommages à l'ADN et peut être rapidement dirigé vers eux. À cet égard, la première question abordée dans cette étude était le lien entre la transcription et la réparation de l'ADN dans le contexte des fonctions FUS dans le noyau. Deuxièmement, la fonction de FUS dans la réparation de l'ADN dépendante de PARP-1 est basée sur sa capacité à se lier à PAR. Alors que d'autres protéines de liaison à l'ARN peuvent également se lier au PAR par le biais d'interactions électrostatiques, FUS a une propension unique à se lier et à être PARylé. Par conséquent, comprendre les caractéristiques structurelles qui rendent FUS unique parmi les autres protéines de liaison à l'ARN et la nature des interactions FUS-PAR peut aider à faire la lumière sur son rôle dans la réparation de l'ADN.Dans cette étude, nous avons utilisé une approche structurelle pour démontrer l'interaction spécifique du domaine RRM unique de FUS avec PAR. Contrairement à d'autres protéines de liaison à l'ARN, les RRM de FUS manquent de résidus aromatiques qui interagissent généralement avec les bases de l'ARN. Notre analyse par spectroscopie RMN montre que cela fournit une base pour l'interaction similaire du FUS RRM avec l'ARN et le PAR. De plus, nous avons cherché à savoir si FUS jouait un rôle dans le contrôle du niveau global de PAR dans le noyau des cellules HeLa suite au stress oxydatif et à l'arrêt de la transcription. Nos résultats indiquent que FUS peut augmenter de manière significative le niveau de PARylation dans les cellules exposées à de faibles concentrations de peroxyde d'hydrogène, un agent de stress oxydatif connu pour activer fortement PARP-1. Cette découverte est cohérente avec le lien entre la transcription et la réparation de l'ADN, car le blocage de la transcription augmente considérablement la capacité de FUS à augmenter le niveau de PAR dans les cellules HeLa exposées au peroxyde d'hydrogène. De plus, nous avons identifié certains résidus situés dans le RRM de FUS, précédemment identifiés comme PARylés, qui contrôlent l'autoPARylation de PARP-1 in vitro et le niveau d'activité de PARP-1 dans les cellules. Dans l'ensemble, ces résultats fournissent une base pour comprendre le rôle spécifique de FUS dans les mécanismes de réparation de l'ADN liés à PARP-1

Relation structure-fonction de FUS, une protéine de liaison à l'ARN, dans la réparation de l'ADN

Cells have evolved complex repair mechanisms to maintain the integrity of their genomes, and one of these mechanisms involves the PARP-1 enzyme and the synthesis of poly(ADP-ribose) (PAR). PARP-1 is recruited to the sites of DNA damage, where it synthesizes long negatively charged PAR chains attached to itself and other acceptor proteins. The PAR chains then act as a scaffold for the recruitment of other proteins, such as DNA repair factors, which are required for proper DNA repair.In recent studies, various RNA-binding proteins (RBPs) have been found to play a role in DNA repair. When considering DNA repair mechanisms that are dependent on PARP-1 activation, it appears that members of the FET family, particularly FUS, play a central role. FUS is recruited to DNA damage sites after laser beam exposure, and this recruitment depends on PARP-1 activity. FUS was identified in mass-spectrometry analyses of PARylated proteins following genotoxic stress and was shown to interact directly with PAR. In addition, FUS was shown to form the compartments through the interactions occurring between its low-complexity domains. Particularly, the formation of such compartments was observed at DNA damage sites following PARP-1 activation.The aim of this study is to investigate the biological functions of FUS in DNA repair mechanisms related to PARP-1 activation. FUS is known to participate in transcription by interacting with the C-terminal domain of RNA pol II and binding to nascent mRNA. Given that DNA damages often occur in open, transcriptionally-active chromatin, FUS is located in close proximity to DNA damage sites and can be rapidly directed to them. In this regard, the first question addressed in this study was the link between transcription and DNA repair in the context of FUS functions in the nucleus. Secondly, we asked whether FUS's function in PARP-1-dependent DNA repair is based on its ability to bind PAR. While other RNA-binding proteins can also bind to PAR through electrostatic interactions, FUS has a unique propensity for binding to and being PARylated. Therefore, understanding the structural characteristics that make FUS unique among other RNA-binding proteins and the nature of FUS-PAR interactions can help shed light on its role in DNA repair.In this study, we utilized a structural approach to demonstrate the specific interaction of the single RRM domain of FUS with protein-free PAR. Unlike other RNA-binding proteins, FET protein RRMs lack several aromatic residues that usually interact with RNA bases. Our NMR spectroscopy analysis shows that this provides a basis for the similar interaction of FUS RRM with RNA and PAR. Furthermore, we investigated whether FUS plays a role in controlling the overall level of PAR in the nucleus of HeLa cells following oxidative stress and transcription arrest. Our results indicate that FUS can significantly increase the level of PARylation in cells exposed to mild concentrations of hydrogen peroxide, an oxidative stress agent known to strongly activate PARP-1. This finding is consistent with the link between transcription and DNA repair, as stalling transcription significantly increases the capacity of FUS to increase the PAR level in HeLa cells exposed to hydrogen peroxide. Additionally, we identified certain residues located in the RRM of FUS, previously identified as PARylated, that control the autoPARylation of PARP-1 in vitro and the level of PARP-1 activity in cells. Overall, these results provide a basis for understanding the specific role of FUS in PARP-1-related DNA repair mechanisms.Les cellules ont développé des mécanismes de réparation complexes pour maintenir l'intégrité de leurs génomes, et l'un de ces mécanismes implique l'enzyme PARP-1 et la synthèse de poly(ADP-ribose) (PAR). PARP-1 est recruté sur les sites de dommages à l'ADN, où il synthétise de longues chaînes PAR chargées négativement attachées à lui-même et à d'autres protéines. Les chaînes PAR agissent alors comme un échafaudage pour le recrutement d'autres protéines, qui sont nécessaires à une réparation correcte de l'ADN.Dans des études récentes, diverses protéines de liaison à l'ARN se sont avérées jouer un rôle dans la réparation de l'ADN. Lorsque l'on considère les mécanismes de réparation de l'ADN qui dépendent de l'activation de PARP-1, il semble que les membres de la famille FET, en particulier FUS, jouent un rôle central. FUS est recruté sur les sites de dommages à l'ADN après exposition au faisceau laser. Il a été identifié dans des analyses par spectrométrie de masse de protéines PARylées suite à un stress génotoxique et il a été démontré qu'il interagit directement avec le PAR. De plus, FUS a été démontré comme formant des compartiments grâce à des interactions entre ses domaines de faible complexité, comme observé au niveau des sites de dommages à l'ADN suite à l'activation de PARP-1.Le but de cette étude est d'étudier les fonctions biologiques de FUS dans les mécanismes de réparation de l'ADN liés à l'activation de PARP-1. FUS est connu pour participer à la transcription en interagissant avec l'ARN Pol II et en se liant à l'ARNm naissant. Étant donné que les dommages à l'ADN se produisent souvent dans la chromatine ouverte et transcriptionnellement active, FUS est situé à proximité des sites de dommages à l'ADN et peut être rapidement dirigé vers eux. À cet égard, la première question abordée dans cette étude était le lien entre la transcription et la réparation de l'ADN dans le contexte des fonctions FUS dans le noyau. Deuxièmement, la fonction de FUS dans la réparation de l'ADN dépendante de PARP-1 est basée sur sa capacité à se lier à PAR. Alors que d'autres protéines de liaison à l'ARN peuvent également se lier au PAR par le biais d'interactions électrostatiques, FUS a une propension unique à se lier et à être PARylé. Par conséquent, comprendre les caractéristiques structurelles qui rendent FUS unique parmi les autres protéines de liaison à l'ARN et la nature des interactions FUS-PAR peut aider à faire la lumière sur son rôle dans la réparation de l'ADN.Dans cette étude, nous avons utilisé une approche structurelle pour démontrer l'interaction spécifique du domaine RRM unique de FUS avec PAR. Contrairement à d'autres protéines de liaison à l'ARN, les RRM de FUS manquent de résidus aromatiques qui interagissent généralement avec les bases de l'ARN. Notre analyse par spectroscopie RMN montre que cela fournit une base pour l'interaction similaire du FUS RRM avec l'ARN et le PAR. De plus, nous avons cherché à savoir si FUS jouait un rôle dans le contrôle du niveau global de PAR dans le noyau des cellules HeLa suite au stress oxydatif et à l'arrêt de la transcription. Nos résultats indiquent que FUS peut augmenter de manière significative le niveau de PARylation dans les cellules exposées à de faibles concentrations de peroxyde d'hydrogène, un agent de stress oxydatif connu pour activer fortement PARP-1. Cette découverte est cohérente avec le lien entre la transcription et la réparation de l'ADN, car le blocage de la transcription augmente considérablement la capacité de FUS à augmenter le niveau de PAR dans les cellules HeLa exposées au peroxyde d'hydrogène. De plus, nous avons identifié certains résidus situés dans le RRM de FUS, précédemment identifiés comme PARylés, qui contrôlent l'autoPARylation de PARP-1 in vitro et le niveau d'activité de PARP-1 dans les cellules. Dans l'ensemble, ces résultats fournissent une base pour comprendre le rôle spécifique de FUS dans les mécanismes de réparation de l'ADN liés à PARP-1

Relation structure-fonction de FUS, une protéine de liaison à l'ARN, dans la réparation de l'ADN

Les cellules ont développé des mécanismes de réparation complexes pour maintenir l'intégrité de leurs génomes, et l'un de ces mécanismes implique l'enzyme PARP-1 et la synthèse de poly(ADP-ribose) (PAR). PARP-1 est recruté sur les sites de dommages à l'ADN, où il synthétise de longues chaînes PAR chargées négativement attachées à lui-même et à d'autres protéines. Les chaînes PAR agissent alors comme un échafaudage pour le recrutement d'autres protéines, qui sont nécessaires à une réparation correcte de l'ADN.Dans des études récentes, diverses protéines de liaison à l'ARN se sont avérées jouer un rôle dans la réparation de l'ADN. Lorsque l'on considère les mécanismes de réparation de l'ADN qui dépendent de l'activation de PARP-1, il semble que les membres de la famille FET, en particulier FUS, jouent un rôle central. FUS est recruté sur les sites de dommages à l'ADN après exposition au faisceau laser. Il a été identifié dans des analyses par spectrométrie de masse de protéines PARylées suite à un stress génotoxique et il a été démontré qu'il interagit directement avec le PAR. De plus, FUS a été démontré comme formant des compartiments grâce à des interactions entre ses domaines de faible complexité, comme observé au niveau des sites de dommages à l'ADN suite à l'activation de PARP-1.Le but de cette étude est d'étudier les fonctions biologiques de FUS dans les mécanismes de réparation de l'ADN liés à l'activation de PARP-1. FUS est connu pour participer à la transcription en interagissant avec l'ARN Pol II et en se liant à l'ARNm naissant. Étant donné que les dommages à l'ADN se produisent souvent dans la chromatine ouverte et transcriptionnellement active, FUS est situé à proximité des sites de dommages à l'ADN et peut être rapidement dirigé vers eux. À cet égard, la première question abordée dans cette étude était le lien entre la transcription et la réparation de l'ADN dans le contexte des fonctions FUS dans le noyau. Deuxièmement, la fonction de FUS dans la réparation de l'ADN dépendante de PARP-1 est basée sur sa capacité à se lier à PAR. Alors que d'autres protéines de liaison à l'ARN peuvent également se lier au PAR par le biais d'interactions électrostatiques, FUS a une propension unique à se lier et à être PARylé. Par conséquent, comprendre les caractéristiques structurelles qui rendent FUS unique parmi les autres protéines de liaison à l'ARN et la nature des interactions FUS-PAR peut aider à faire la lumière sur son rôle dans la réparation de l'ADN.Dans cette étude, nous avons utilisé une approche structurelle pour démontrer l'interaction spécifique du domaine RRM unique de FUS avec PAR. Contrairement à d'autres protéines de liaison à l'ARN, les RRM de FUS manquent de résidus aromatiques qui interagissent généralement avec les bases de l'ARN. Notre analyse par spectroscopie RMN montre que cela fournit une base pour l'interaction similaire du FUS RRM avec l'ARN et le PAR. De plus, nous avons cherché à savoir si FUS jouait un rôle dans le contrôle du niveau global de PAR dans le noyau des cellules HeLa suite au stress oxydatif et à l'arrêt de la transcription. Nos résultats indiquent que FUS peut augmenter de manière significative le niveau de PARylation dans les cellules exposées à de faibles concentrations de peroxyde d'hydrogène, un agent de stress oxydatif connu pour activer fortement PARP-1. Cette découverte est cohérente avec le lien entre la transcription et la réparation de l'ADN, car le blocage de la transcription augmente considérablement la capacité de FUS à augmenter le niveau de PAR dans les cellules HeLa exposées au peroxyde d'hydrogène. De plus, nous avons identifié certains résidus situés dans le RRM de FUS, précédemment identifiés comme PARylés, qui contrôlent l'autoPARylation de PARP-1 in vitro et le niveau d'activité de PARP-1 dans les cellules. Dans l'ensemble, ces résultats fournissent une base pour comprendre le rôle spécifique de FUS dans les mécanismes de réparation de l'ADN liés à PARP-1.Cells have evolved complex repair mechanisms to maintain the integrity of their genomes, and one of these mechanisms involves the PARP-1 enzyme and the synthesis of poly(ADP-ribose) (PAR). PARP-1 is recruited to the sites of DNA damage, where it synthesizes long negatively charged PAR chains attached to itself and other acceptor proteins. The PAR chains then act as a scaffold for the recruitment of other proteins, such as DNA repair factors, which are required for proper DNA repair.In recent studies, various RNA-binding proteins (RBPs) have been found to play a role in DNA repair. When considering DNA repair mechanisms that are dependent on PARP-1 activation, it appears that members of the FET family, particularly FUS, play a central role. FUS is recruited to DNA damage sites after laser beam exposure, and this recruitment depends on PARP-1 activity. FUS was identified in mass-spectrometry analyses of PARylated proteins following genotoxic stress and was shown to interact directly with PAR. In addition, FUS was shown to form the compartments through the interactions occurring between its low-complexity domains. Particularly, the formation of such compartments was observed at DNA damage sites following PARP-1 activation.The aim of this study is to investigate the biological functions of FUS in DNA repair mechanisms related to PARP-1 activation. FUS is known to participate in transcription by interacting with the C-terminal domain of RNA pol II and binding to nascent mRNA. Given that DNA damages often occur in open, transcriptionally-active chromatin, FUS is located in close proximity to DNA damage sites and can be rapidly directed to them. In this regard, the first question addressed in this study was the link between transcription and DNA repair in the context of FUS functions in the nucleus. Secondly, we asked whether FUS's function in PARP-1-dependent DNA repair is based on its ability to bind PAR. While other RNA-binding proteins can also bind to PAR through electrostatic interactions, FUS has a unique propensity for binding to and being PARylated. Therefore, understanding the structural characteristics that make FUS unique among other RNA-binding proteins and the nature of FUS-PAR interactions can help shed light on its role in DNA repair.In this study, we utilized a structural approach to demonstrate the specific interaction of the single RRM domain of FUS with protein-free PAR. Unlike other RNA-binding proteins, FET protein RRMs lack several aromatic residues that usually interact with RNA bases. Our NMR spectroscopy analysis shows that this provides a basis for the similar interaction of FUS RRM with RNA and PAR. Furthermore, we investigated whether FUS plays a role in controlling the overall level of PAR in the nucleus of HeLa cells following oxidative stress and transcription arrest. Our results indicate that FUS can significantly increase the level of PARylation in cells exposed to mild concentrations of hydrogen peroxide, an oxidative stress agent known to strongly activate PARP-1. This finding is consistent with the link between transcription and DNA repair, as stalling transcription significantly increases the capacity of FUS to increase the PAR level in HeLa cells exposed to hydrogen peroxide. Additionally, we identified certain residues located in the RRM of FUS, previously identified as PARylated, that control the autoPARylation of PARP-1 in vitro and the level of PARP-1 activity in cells. Overall, these results provide a basis for understanding the specific role of FUS in PARP-1-related DNA repair mechanisms

Surface modification of biomaterials based on high-molecular polylactic acid and their effect on inflammatory reactions of primary human monocyte-derived macrophages: perspective for personalized therapy

Polylactic acid (PLA) based implants can cause inflammatory complications. Macrophages are key innate immune cells that control inflammation. To provide higher biocompatibility of PLA-based implants with local innate immune cells their surface properties have to be improved. In our study surface modification technique for high-molecular PLA (MW=1,646,600g/mol) based biomaterials was originally developed and successfully applied. Optimal modification conditions were determined. Treatment of PLA films with toluene/ethanol=3/7 mixture for 10min with subsequent exposure in 0.001M brilliant green dye (BGD) solution allows to entrap approximately 10(-9)mol/cm(2) model biomolecules. The modified PLA film surface was characterized by optical microscopy, SERS, FT-IR, UV and TG/DTA/DSC analysis. Tensile strain of modified films was determined as well. The effect of PLA films modified with BGD on the inflammatory reactions of primary human monocyte-derived macrophages was investigated. We developed in vitro test-system by differentiating primary monocyte-derived macrophages on a coating material. Type 1 and type 2 inflammatory cytokines (TNFα, CCL18) secretion and histological biomarkers (CD206, stabilin-1) expression were analyzed by ELISA and confocal microscopy respectively. BGD-modified materials have improved thermal stability and good mechanical properties. However, BGD modifications induced additional donor-specific inflammatory reactions and suppressed tolerogenic phenotype of macrophages. Therefore, our test-system successfully demonstrated specific immunomodulatory effects of original and modified PLA-based biomaterials, and can be further applied for the examination of improved coatings for implants and identification of patient-specific reactions to implants

Surface modification of biomaterials based on high-molecular polylactic acid and their effect on inflammatory reactions of primary human monocyte-derived macrophages: perspective for personalized therapy

Polylactic acid (PLA) based implants can cause inflammatory complications. Macrophages are key innate immune cells that control inflammation. To provide higher biocompatibility of PLA-based implants with local innate immune cells their surface properties have to be improved. In our study surface modification technique for high-molecular PLA (MW=1,646,600g/mol) based biomaterials was originally developed and successfully applied. Optimal modification conditions were determined. Treatment of PLA films with toluene/ethanol=3/7 mixture for 10min with subsequent exposure in 0.001M brilliant green dye (BGD) solution allows to entrap approximately 10(-9)mol/cm(2) model biomolecules. The modified PLA film surface was characterized by optical microscopy, SERS, FT-IR, UV and TG/DTA/DSC analysis. Tensile strain of modified films was determined as well. The effect of PLA films modified with BGD on the inflammatory reactions of primary human monocyte-derived macrophages was investigated. We developed in vitro test-system by differentiating primary monocyte-derived macrophages on a coating material. Type 1 and type 2 inflammatory cytokines (TNFα, CCL18) secretion and histological biomarkers (CD206, stabilin-1) expression were analyzed by ELISA and confocal microscopy respectively. BGD-modified materials have improved thermal stability and good mechanical properties. However, BGD modifications induced additional donor-specific inflammatory reactions and suppressed tolerogenic phenotype of macrophages. Therefore, our test-system successfully demonstrated specific immunomodulatory effects of original and modified PLA-based biomaterials, and can be further applied for the examination of improved coatings for implants and identification of patient-specific reactions to implants

FUS RRM regulates poly(ADP-ribose) levels after transcriptional arrest and PARP-1 activation on DNA damage

PARP-1 activation at DNA damage sites leads to the synthesis of long poly(ADP-ribose) (PAR) chains, whichserve as a signal for DNA repair. Here we show that FUS, an RNA-binding protein, is specifically directed toPAR through its RNA recognition motif (RRM) to increase PAR synthesis by PARP-1 in HeLa cells after genotoxicstress. Using a structural approach, we also identify specific residues located in the FUS RRM, whichcan be PARylated by PARP-1 to control the level of PAR synthesis. Based on the results of this work, we proposea model in which, following a transcriptional arrest that releases FUS from nascent mRNA, FUS can berecruited by PARP-1 activated by DNA damage to stimulate PAR synthesis. We anticipate that this modeloffers new perspectives to understand the role of FET proteins in cancers and in certain neurodegenerativediseases such as amyotrophic lateral sclerosis

Epma-World Congress 2015

A1 Predictive and prognostic biomarker panel for targeted application of radioembolisation improving individual outcomes in hepatocellular carcinoma, Jella-Andrea Abraham, Olga Golubnitschaja, A2 Integrated market access approach amplifying value of “Rx-CDx”, Ildar Akhmetov, A3 Disaster response: an opportunity to improve global healthcare, Russell J. Andrews, Leonidas Quintana, A4 USA PPPM: proscriptive, profligate, profiteering medicine-good for 1 % wealthy, not for 99 % unhealthy, Russell J. Andrews, A5 The role of IDO in a murine model of gingivitis: predictive and therapeutic potentials, Babak Baban, Jun Yao Liu, Xu Qin, Tailing Wang, Mahmood S. Mozaffari, A6 Specific diets for personalised treatment of diabetes type 2, Viktoriia V. Bati, Tamara V. Meleshko, Olga B. Levchuk, Nadiya V. Boyko, A7 Towards personalized physiotherapeutic approach, Joanna Bauer, Ewa Boerner, Halina Podbielska, A8 Cells, animal, SHIME and in silico models for detection and verification of specific biomarkers of non-communicable chronic diseases, Alojz Bomba, Viktor O. Petrov, Volodymyr G. Drobnych, Rostyslav V. Bubnov, Oksana M. Bykova, Nadiya V. Boyko, A9 INTERACT-chronic care model: Self-treatment by patients with decision support e-Health solution, Hans-Peter Brunner-La Rocca, Lutz Fleischhacker, Olga Golubnitschaja, Frank Heemskerk, Thomas Helms, Tiny Jaarsma, Judita Kinkorova, Jan Ramaekers, Peter Ruff, Ivana Schnur, Emilio Vanoli, Jose Verdu, A10 PPPM in cardiovascular medicine in 2015, Hans-Peter Brunner-La Rocca, A11 Magnetic resonance imaging of nanoparticles in mice, potential for theranostic and contrast media development – pilot results, Rostyslav V. Bubnov, Sergiy A. Grabovetskyi, Olena M. Mykhalchenko, Natalia O. Tymoshok, Oleksandr B. Shcherbakov, Igor P. Semeniv, Mykola Y. Spivak, A12 Ultrasound diagnosis for diabetic neuropathy - comparative study, Rostyslav V. Bubnov, Tetyana V. Ostapenko, A13 Ultrasound for stratification patients with diabetic foot ulcers for prevention and personalized treatment - pilot results, Rostyslav V. Bubnov, Nazarii M. Kobyliak, Nadiya M. Zholobak, Mykola Ya. Spivak, A14 Project ImaGenX – designing and executing a questionnaire on environment and lifestyle risk of breast cancer, John Paul Cauchi, A15 Genomics – a new structural brand of predictive, preventive and personalized medicine or the new driver as well?, Dmitrii Cherepakhin, Marina Bakay, Artem Borovikov, Sergey Suchkov, A16 Survey of questionnaires for evaluation of the quality of life in various medical fields, Barbara Cieślik, Agnieszka Migasiewicz, Maria-Luiza Podbielska, Markus Pelleter, Agnieszka Giemza, Halina Podbielska, A17 Personalized molecular treatment for muscular dystrophies, Sebahattin Cirak, A18 Secondary mutations in circulating tumour DNA for acquired drug resistance in patients with advanced ALK + NSCLC, Marzia Del Re, Paola Bordi, Valentina Citi, Marta Palombi, Carmine Pinto, Marcello Tiseo, Romano Danesi, A19 Recombinant species-specific FcεRI alpha proteins for diagnosis of IgE-mediated allergies in dogs, cats and horses, Lukas Einhorn, Judit Fazekas, Martina Muhr, Alexandra Schoos, Lucia Panakova, Ina Herrmann, Krisztina Manzano-Szalai, Kumiko Oida, Edda Fiebiger, Josef Singer, Erika Jensen-Jarolim, A20 Global methodology for developmental neurotoxicity testing in humans and animals early and chronically exposed to chemical contaminants, Arpiné A. Elnar, Nadia Ouamara, Nadiya Boyko, Xavier Coumoul, Jean-Philippe Antignac, Bruno Le Bizec, Gauthier Eppe, Jenny Renaut, Torsten Bonn, Cédric Guignard, Margherita Ferrante, Maria Liusa Chiusano, Salvatore Cuzzocrea, Gerard O'Keeffe, John Cryan, Michelle Bisson, Amina Barakat, Ihsane Hmamouchi, Nasser Zawia, Anumantha Kanthasamy, Glen E. Kisby, Rui Alves, Oscar Villacañas Pérez, Kim Burgard, Peter Spencer, Norbert Bomba, Martin Haranta, Nina Zaitseva, Irina May, Stéphanie Grojean, Mathilde Body-Malapel, Florencia Harari, Raul Harari, Kristina Yeghiazaryan, Olga Golubnitschaja, Vittorio Calabrese, Christophe Nemos, Rachid Soulimani, A21 Mental indicators at young people with attributes hypertension and pre-hypertension, Maria E. Evsevyeva, Elena A. Mishenko, Zurida V. Kumukova, Evgeniy V. Chudnovsky, Tatyana A. Smirnova, A22 On the approaches to the early diagnosis of stress-induced hypertension in young employees of State law enforcement agencies, Maria E. Evsevyeva, Ludmila V. Ivanova, Michail V. Eremin, Maria V. Rostovtseva, A23 Сentral aortic pressure and indexes of augmentation in young persons in view of risk factors, Maria E. Evsevyeva, Michail V. Eremin, Vladimir I. Koshel, Oksana V. Sergeeva, Nadesgda M. Konovalova, A24 Breast cancer prediction and prevention: Are reliable biomarkers in horizon?, Shantanu Girotra, Olga Golubnitschaja, A25 Flammer Syndrome and potential formation of pre-metastatic niches: A multi-centred study on phenotyping, patient stratification, prediction and potential prevention of aggressive breast cancer and metastatic disease, Olga Golubnitschaja, Manuel Debald, Walther Kuhn, Kristina Yeghiazaryan, Rostyslav V. Bubnov, Vadym M. Goncharenko, Ulyana Lushchyk, Godfrey Grech, Katarzyna Konieczka, A26 Innovative tools for prenatal diagnostics and monitoring: improving individual pregnancy outcomes and health-economy in EU, Olga Golubnitschaja, Jan Jaap Erwich, Vincenzo Costigliola, Kristina Yeghiazaryan, Ulrich Gembruch, A27 Immunohistochemical assessment of APUD cells in endometriosis, Vadym M. Goncharenko, Vasyl O. Beniuk, Olga V. Kalenska, Rostyslav V. Bubnov, A28 Updating personalized management algorithm of endometrial hyperplasia in pre-menopause women, Vadym M. Goncharenko, Vasyl O. Beniuk, Rostyslav V. Bubnov, Olga Melnychuk, A29 The personified treatment approach of polimorbid patients with periodontal inflammatory diseases, Irina A. Gorbacheva, Lyudmila Y. Orekhova, Vadim V. Tachalov, A30 Ukrainian experience in hybrid war – the challenge to update algorithms for personalized care and early prevention of different military injuries, Olena I. Grechanyk, Rizvan Ya. Abdullaiev, Rostyslav V. Bubnov, A31 Tear fluid biomarkers: a comparison of tear fluid sampling and storage protocols, Suzanne Hagan, Eilidh Martin, Ian Pearce, Katherine Oliver, A32 The correlation of dietary habits with gingival problems during menstruation, Cenk Haytac, Fariz Salimov, Servin Yoksul, Anatoly A. Kunin, Natalia S. Moiseeva, A33 Genomic medicine in a contemporary Spanish population of prostate cancer: our experience, Bernardo Herrera-Imbroda, Sergio del Río-González, Maria Fernanda Lara, Antonia Angulo, Francisco Javier Machuca Santa-Cruz, A34 Challenges, opportunities and collaborations for personalized medicine applicability in uro-oncological disease, Bernardo Herrera-Imbroda, Sergio del Río-González, Maria Fernanda Lara, A35 Metabolic hallmarks of cancer as targets for a personalized therapy, John Ionescu, A36 Influence of genetic polymorphism as a predictor of the development of periodontal disease in patients with gastric ulcer and 12 duodenal ulcer, Alfiya Z. Isamulaeva, Anatoly A. Kunin, Shamil Sh. Magomedov, Aida I. Isamulaeva, A37 Challenges in diabetic macular edema, Tatjana Josifova, A38 Overview of the EPMA strategies in laboratory medicine relevant for PPPM, Marko Kapalla, Juraj Kubáň, Olga Golubnitschaja, Vincenzo Costigliola, A39 EPMA initiative for effective organization of medical travel: European concepts and criteria, Vincenzo Costigliola, Marko Kapalla, Juraj Kubáň, Olga Golubnitschaja, A40 Design and innovation in e-textiles: implications for PPPM, Anthony Kent, Tom Fisher, Tilak Dias, A41 Biobank in Pilsen as a member of national node BBMRI_CZ, Judita Kinkorová, Ondřej Topolčan, A42 Big data in personalized medicine: hype and hope, Matthias Kohl, A43 The 3P approach as the platform of the European Dentistry Department (DPPPD), Anatoly A. Kunin, Natalia S. Moiseeva, A44 The endometrium cytokine patterns for predictive diagnosis of proliferation severity and cancer prevention, Andrii I. Kurchenko, Vasyl A. Beniuk, Vadym M. Goncharenko, Rostyslav V. Bubnov, Nadiya V. Boyko, Andriy M. Strokan, A45 A monocyte-based in-vitro system for testing individual responses to the implanted material: future for personalized implant construction, Julia Kzhyshkowska, Alexandru Gudima, Ksenia S. Stankevich, Victor D. Filimonov4, Harald Klüter, Evgeniya M. Mamontova, Sergei I. Tverdokhlebov, A46 Prediction and prevention of adverse health effects by meteorological factors: Biomarker patterns and creation of a device for self-monitoring and integrated care, Ulyana B. Lushchyk, Viktor V. Novytskyy, Igor P. Babii, Nadiya G. Lushchyk, Lyudmyla S. Riabets, Ivanna I. Legka, A47 Targeting "disease signatures" towards personalized healthcare, Mira Marcus-Kalish, Alexis Mitelpunkt, Tal Galili, Neta Shachar, Yoav Benjamini, A48 Influence of the skin imperfection on the personal quality of life and possible tools for objective diagnosis, Agnieszka Migasiewicz, Markus Pelleter, Joanna Bauer, Ewelina Dereń, Halina Podbielska, A49 The new direction in caries prevention based on the ultrastructure of dental hard tissues and filling materials, Natalia S. Moiseeva, Anatoly A. Kunin, Dmitry A. Kunin, A50 The use of LED radiation in prevention of dental diseases, Natalia S. Moiseeva, Yury A. Ippolitov, Dmitry A. Kunin, Alexei N. Morozov, Natalia V. Chirkova, Nakhid T. Aliev, A51 Status of endothelial progenitor cells in diabetic nephropathy: predictive and preventive potentials, Mahmood S. Mozaffari, Jun Yao Liu, Babak Baban, A52 The status of glucocorticoid-induced leucine zipper protein in salivary gland in Sjögren’s syndrome: predictive and personalized treatment potentials, Mahmood S. Mozaffari, Jun Yao Liu, Rafik Abdelsayed, Xing-Ming Shi, Babak Baban, A53 Maximal aerobic capacity - important quality marker of health, Jaroslav Novák, Milan Štork, Václav Zeman, A54 The EMPOWER project: laboratory medicine and Horizon 2020, Wytze P. Oosterhuis, Elvar Theodorsson, A55 Personality profile manifestations in patient’s attitude to oral care and adherence to doctor’s prescriptions, Lyudmila Y. Orekhova, Tatyana V. Kudryavtseva, Elena R. Isaeva, Vadim V. Tachalov, Ekaterina S. Loboda, A56 Results of an European survey on personalized medicine addressed to directions of laboratory medicine, Mario Pazzagli, Francesca Malentacchi, Irene Mancini, Ivan Brandslund, Pieter Vermeersch, Matthias Schwab, Janja Marc, Ron H.N. van Schaik, Gerard Siest, Elvar Theodorsson, Chiara Di Resta, A57 MCI or early dementia predictive speech based diagnosis techniques, Matus Pleva, Jozef Juhar, A58 Personalized speech based mobile application for eHealth, Matus Pleva, Jozef Juhar, A59 Circulating tumor cell-free DNA as the biomarker in the management of cancer patients, Jiří Polívka jr., Filip Janků, Martin Pešta, Jan Doležal, Milena Králíčková, Jiří Polívka, A60 Complex stroke care – educational programme in Stroke Centre University Hospital Plzen, Jiří Polívka, Alena Lukešová, Nina Müllerová, Petr Ševčík, Vladimír Rohan, A61 Sleep apnea and sleep fragmentation contribute to brain aging, Kneginja Richter, Lence Miloseva, Günter Niklewski, A62 Personalised approach for sleep disturbances in shift workers, Kneginja Richter, Jens Acker, Guenter Niklewski, A63 Medical travel and innovative PPPM clusters: new concept of integration, Olga Safonicheva, Vincenzo Costigliola, A64 Medical travel and women health, Olga Safonicheva, A65 Continuity of generations in the training of specialists in the field of reconstructive microsurgery, Maxim Sautin, Janna Sinelnikova, Sergey Suchkov, A66 Telemonitoring of stroke patients – empirical evidence of individual risk management results from an observational study in Germany, Songül Secer, Stephan von Bandemer, A67 Women’s increasing breast cancer risk with n-6 fatty acid intake explained by estrogen-fatty acid interactive effect on DNA damage: implications for gender-specific nutrition within personalized medicine, Niva Shapira, A68 Cytobacterioscopy of the gingival crevicular fluid as a method for preventive diagnosis of periodontal diseases, Aleksandr Shcherbakov, Anatoly A. Kunin, Natalia S. Moiseeva, A69 Use of specially treated composites in dentistry to avoid violations of aesthetics, Bogdan R. Shumilovich, Zhanna Lipkind, Yulia Vorobieva, Dmitry A. Kunin, Anastasiia V. Sudareva, A70 National eHealth system – platform for preventive, predictive and personalized diabetes care, Ivica Smokovski, Tatjana Milenkovic, A72 The common energy levels of Prof. Szent-Györgyi, the intrinsic chemistry of melanin, and the muscle physiopathology. Implications in the context of Preventive, Predictive, and Personalized Medicine, Arturo Solís-Herrera, María del Carmen Arias-Esparza, Sergey Suchkov, A73 Plurality and individuality of hepatocellular carcinoma: PPPM perspectives, Krishna Chander Sridhar, Olga Golubnitschaja, A74 Strategic aspects of higher medical education reforms to secure newer educational platforms for getting biopharma professionals matures, Maria Studneva, Sihong Song, James Creeden, Мark Мandrik, Sergey Suchkov, A75 Overview of the strategies and activities of the European Federation of Clinical Chemistry and Laboratory Medicine, (EFLM), Elvar Theodorsson, EFLM, A76 New spectroscopic techniques for point of care label free diagnostics, Syed A. M. Tofail, A77 Tumor markers for personalized medicine and oncology - the role of Laboratory Medicine, Ondřej Topolčan, Judita Kinkorová, Ondřej Fiala, Marie Karlíková, Šárka Svobodová, Radek Kučera, Radka Fuchsová, Vladislav Třeška, Václav Šimánek, Ladislav Pecen, Jan Šoupal, Štěpán Svačina2, A78 Modern medical terminology (MMT) as a driver of the global educational reforms, Evgeniya Tretyak, Maria Studneva, Sergey Suchkov, A79 Juvenile hypertension; the relevance of novel predictive, preventive and personalized assessment of its determinants, Francesca M. Trovato, G. Fabio Martines, Daniela Brischetto, Daniela Catalano, Giuseppe Musumeci, Guglielmo M. Trovato, A80 Proteomarkers Biotech, George Th. Tsangaris, Athanasios K. Anagnostopoulos, A81 Proteomics and mass spectrometry based non-invasive prenatal testing of fetal health and pregnancy complications, George Th. Tsangaris, Athanasios K. Anagnostopoulos, A82 Integrated Ecosystem for an Integrated Care model for Heart Failure (HF) patients including related comorbidities (ZENITH), José Verdú, German Gutiérrez, Jordi Rovira, Marta Martinez, Lutz Fleischhacker, Donna Green, Arthur Garson, Elena Tamburini, Stefano Cuomo, Juan Martinez-Leon, Teresa Abrisqueta, Hans-Peter Brunner-La Rocca, Tiny Jaarsma, Teresa Arredondo, Cecilia Vera, Giuseppe Fico, Olga Golubnitschaja, Fernando Arribas, Martina Onderco, Isabel Vara, on behalf of ZENITH consortium, A83 Predictive, preventive and personalized medicine in diabetes onset and complication (MOSAIC project), José Verdú, Francesco Sambo, Barbara Di Camillo, Claudio Cobelli, Andrea Facchinetti, Giuseppe Fico, Riccardo Bellazzi, Lucia Sacchi, Arianna Dagliati, Daniele Segnani, Valentina Tibollo, Manuel Ottaviano, Rafael Gabriel, Leif Groop, Jacqueline Postma, Antonio Martinez, Liisa Hakaste, Tiinamaija Tuomi, Konstantia Zarkogianni, on behalf of MOSAIC consortium, A84 Possibilities for personalized therapy of diabetes using in vitro screening of insulin and oral hypoglycemic agents, Igor Volchek, Nina Pototskaya, Andrey Petrov, A85 The innovative technology for personalized therapy of human diseases based on in vitro drug screening, Igor Volchek, Nadezhda Pototskaya, Andrey Petrov, A86 Bone destruction and temporomandibular joint: predictive markers, pathogenetic aspects and quality of life, Ülle Voog-Oras, Oksana Jagur, Edvitar Leibur, Priit Niibo, Triin Jagomägi, Minh Son Nguyen, Chris Pruunsild, Dagmar Piikov, Mare Saag, A87 Sub-optimal health management – global vision for concepts in medical travel, Wei Wang, A88 Sub-optimal health management: synergic PPPM-TCAM approach, Wei Wang, A89 Innovative technologies for minimal invasive diagnostics, Andreas Weinhäusel, Walter Pulverer, Matthias Wielscher, Manuela Hofner, Christa Noehammer, Regina Soldo, Peter Hettegger, Istvan Gyurjan, Ronald Kulovics, Silvia Schönthaler, Gabriel Beikircher, Albert Kriegner, Stephan Pabinger, Klemens Vierlinger, A90 Rare disease diobanks for personalized medicine, Ayşe Yüzbaşıoğlu, Meral Özgüç, Member of EuroBioBank - European Network of DNA, Cell and Tissue Banks for Rare DiseasesPubMe