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Lorenz, Matthias ; Gao, Lu ; Ziegelbauer, Kathrin ; Norata, Giuseppe Danilo ; Empana, Jean Philippe ; Schmidtmann, Irene ; Lin, Hung-Ju ; McLachlan, Stela ; Bokemark, Lena ; Ronkainen, Kimmo ; Amato, Mauro ; Schminke, Ulf ; Srinivasan, Sathanur R. ; Lind, Lars ; Okazaki, Shuhei ; Stehouwer, Coen D. A. ; Willeit, Peter ; Polak, Joseph F. ; Steinmetz, Helmuth ; Sander, Dirk ; Poppert, Holger ; Desvarieux, Moise ; Ikram, M. Arfan ; Johnsen, Stein Harald ; Staub, Daniel ; Sirtori, Cesare R. ; Iglseder, Bernhard ; Beloqui, Oscar ; Engström, Gunnar ; Friera, Alfonso ; Rozza, Francesco ; Xie, Wuxiang ; Parraga, Grace ; Grigore, Liliana ; Plichart, Matthieu ; Blankenberg, Stefan ; Su, Ta-Chen ; Schmidt, Caroline ; Tuomainen, Tomi-Pekka ; Veglia, Fabrizio ; Völzke, Henry ; Nijpels, Giel ; Willeit, Johann ; Sacco, Ralph L. ; Franco, Oscar H. ; Uthoff, Heiko ; Hedblad, Bo ; Suarez, Carmen ; Izzo, Raffaele ; Zhao, Dong ; Wannarong, Thapat ; Catapano, Alberico ; Ducimetiere, Pierre ; Espinola-Klein, Christine ; Chien, Kuo-Liong ; Price, Jackie F. ; Bergström, Göran ; Kauhanen, Jussi ; Tremoli, Elena ; Dörr, Marcus ; Berenson, Gerald ; Kitagawa, Kazuo ; Dekker, Jacqueline M. ; Kiechl, Stefan ; Sitzer, Matthias ; Bickel, Horst ; Rundek, Tatjana ; Hofman, Albert ; Mathiesen, Ellisiv B. ; Castelnuovo, Samuela ; Landecho, Manuel F. ; Rosvall, Maria ; Gabriel, Rafael ; De Luca, Nicola ; Liu, Jing ; Baldassarre, Damiano ; Kavousi, Maryam ; De Groot, Eric ; Bots, Michiel L. ; Yanez, David N. ; Thompson, Simon G.
Aims: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk.
Methods and results: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies.
In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95–1.02) in group A, 0.98 (0.93–1.04) in group B, and 0.95 (0.89–1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07–1.23) in group A, 1.13 (1.05–1.22) in group B, and 1.12 (1.05–1.20) in group C.
Conclusions: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.
Escott-Price, Valentina ; Bellenguez, Céline ; Wang, Li-San ; Choi, Seung-Hoan ; Harold, Denise ; Jones, Lesley ; Holmans, Peter ; Gerrish, Amy ; Vedernikov, Alexey ; Richards, Alexander ; DeStefano, Anita L. ; Lambert, Jean-Charles ; Ibrahim-Verbaas, Carla A. ; Naj, Adam C. ; Sims, Rebecca ; Jun, Gyungah ; Bis, Joshua C. ; Beecham, Gary W. ; Grenier-Boley, Benjamin ; Russo, Giancarlo ; Thornton-Wells, Tricia A. ; Denning, Nicola ; Smith, Albert V. ; Chouraki, Vincent ; Thomas, Charlene ; Ikram, M. Arfan ; Zelenika, Diana ; Vardarajan, Badri N. ; Kamatani, Yoichiro ; Lin, Chiao-Feng ; Schmidt, Helena ; Kunkle, Brian ; Dunstan, Melanie L. ; Vronskaya, Maria ; Johnson, Andrew D. ; Ruiz, Agustin ; Bihoreau, Marie-Thérèse ; Reitz, Christiane ; Pasquier, Florence ; Hollingworth, Paul ; Hanon, Olivier ; Fitzpatrick, Annette L. ; Buxbaum, Joseph D. ; Campion, Dominique ; Crane, Paul K. ; Baldwin, Clinton ; Becker, Tim ; Gudnason, Vilmundur ; Cruchaga, Carlos ; Craig, David ; Amin, Najaf ; Berr, Claudine ; Lopez, Oscar L. ; Jager, Philip L. De ; Deramecourt, Vincent ; Johnston, Janet A. ; Evans, Denis ; Lovestone, Simon ; Letenneur, Luc ; Hernández, Isabel ; Rubinsztein, David C. ; Eiriksdottir, Gudny ; Sleegers, Kristel ; Goate, Alison M. ; Fiévet, Nathalie ; Huentelman, Matthew J. ; Gill, Michael ; Brown, Kristelle ; Kamboh, M. Ilyas ; Keller, Lina ; Barberger-Gateau, Pascale ; McGuinness, Bernadette ; Larson, Eric B. ; Myers, Amanda J. ; Dufouil, Carole ; Todd, Stephen ; Wallon, David ; Love, Seth ; Rogaeva, Ekaterina ; Gallacher, John ; St George-Hyslop, Peter ; Clarimon, Jordi ; Lleo, Alberto ; Bayer, Anthony ; Tsuang, Debby W. ; Yu, Lei ; Tsolaki, Magda ; Bossù, Paola ; Spalletta, Gianfranco ; Proitsi, Petra ; Collinge, John ; Sorbi, Sandro ; Sanchez Garcia, Florentino ; Fox, Nick C. ; Hardy, John ; Deniz Naranjo, Maria Candida ; Bosco, Paolo ; Clarke, Robert ; Brayne, Carol ; Galimberti, Daniela ; Scarpini, Elio ; Bonuccelli, Ubaldo ; Mancuso, Michelangelo ; Siciliano, Gabriele ; Moebus, Susanne ; Mecocci, Patrizia ; Del Zompo, Maria ; Maier, Wolfgang ; Hampel, Harald ; Pilotto, Alberto ; Frank-García, Ana ; Panza, Francesco ; Solfrizzi, Vincenzo ; Caffarra, Paolo ; Nacmias, Benedetta ; Perry, William ; Mayhaus, Manuel ; Lannfelt, Lars ; Hakonarson, Hakon ; Pichler, Sabrina ; Carrasquillo, Minerva M. ; Ingelsson, Martin ; Beekly, Duane ; Alvarez, Victoria ; Zou, Fanggeng ; Valladares, Otto ; Younkin, Steven G. ; Coto, Eliecer ; Hamilton-Nelson, Kara L. ; Gu, Wei ; Razquin, Cristina ; Pastor, Pau ; Mateo, Ignacio ; Owen, Michael J. ; Faber, Kelley M. ; Jonsson, Palmi V. ; Combarros, Onofre ; O'Donovan, Michael C. ; Cantwell, Laura B. ; Soininen, Hilkka ; Blacker, Deborah ; Mead, Simon ; Mosley, Thomas H. ; Bennett, David A. ; Harris, Tamara B. ; Fratiglioni, Laura ; Holmes, Clive ; Bruijn, Renee F. A. G. de ; Passmore, Peter ; Montine, Thomas J. ; Bettens, Karolien ; Rotter, Jerome I. ; Brice, Alexis ; Morgan, Kevin ; Foroud, Tatiana M. ; Kukull, Walter A. ; Hannequin, Didier ; Powell, John F. ; Nalls, Michael A. ; Ritchie, Karen ; Lunetta, Kathryn L. ; Kauwe, John S. K. ; Boerwinkle, Eric ; Riemenschneider, Matthias ; Boada, Mercè ; Hiltunen, Mikko ; Martin, Eden R. ; Schmidt, Reinhold ; Rujescu, Dan ; Dartigues, Jean-François ; Mayeux, Richard ; Tzourio, Christophe ; Hofman, Albert ; Nöthen, Markus Maria ; Graff, Caroline ; Psaty, Bruce M. ; Haines, Jonathan L. ; Lathrop, Mark ; Pericak-Vance, Margaret Ann ; Launer, Lenore J. ; Broeckhoven, Christine Van ; Farrer, Lindsay A. ; Duijn, Cornelia M. van ; Ramirez, Alfredo ; Seshadri, Sudha ; Schellenberg, Gerard D. ; Amouyel, Philippe ; Williams, Julie
Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.
Principal findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10−6) and 14 (IGHV1-67 p = 7.9×10−8) which indexed novel susceptibility loci.
Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
Breideband, Louise ; Wächtershäuser, Kaja N. ; Hafa, Levin ; Wieland, Konstantin ; Frangakis, Achilleas S. ; Stelzer, Ernst H. K. ; Pampaloni, Francesco
A widespread application of 3D bioprinting in basic and translational research requires accessibility to affordable printers able to produce physiologically relevant tissue models. To facilitate the use of bioprinting as a standard technique in biology, an open-source device based on a consumer-grade 3D stereolithography apparatus (SLA) printer is developed. This SLA bioprinter can produce complex constructs that preserve cell viability and recapitulate the physiology of tissues. The detailed documentation of the modifications apported to the printer as well as a throughout performance analysis allow for a straightforward adoption of the device in other labs and its customization for specific applications. Given the low cost, several modified bioprinters could be simultaneously operated for a parallelized tissue production. To showcase the capability of the bioprinter, constructs consisting of patient-derived cholangiocarcinoma organoids encapsulated in a gelatin methacrylate (GelMA)/polyethylene glycol diacrylate (PEGDA) hydrogel are produced. A thorough characterization of different GelMA/PEGDA ratios reveals that the mechanical properties of the bioprinted tumor model can be accurately fine-tuned to mimic a specific tumor micro-environment. Immunofluorescence and gene expression analyses of tumor markers confirm that the bioprinted synthetic hydrogel provides a flexible and adequate replacement of animal-derived reconstituted extracellular matrix.
Sylvester, Francisco ; Weichert, Fabian G. ; Lozano, Verónica L. ; Groh, Ksenia J. ; Bálint, Miklós ; Baumann, Lisa ; Bässler, Claus ; Brack, Werner ; Brandl, Barbara ; Curtius, Joachim ; Dierkes, Paul ; Döll, Petra ; Ebersberger, Ingo ; Fragkostefanakis, Sotirios ; Helfrich, Eric J. N. ; Hickler, Thomas ; Johann, Sarah ; Jourdan, Jonas ; Klimpel, Sven ; Kminek, Helge ; Liquin, Florencia ; Möllendorf, Darrel ; Mueller, Thomas ; Oehlmann, Jörg ; Ottermanns, Richard ; Pauls, Steffen U. ; Piepenbring, Meike ; Pfefferle, Jakob ; Schenk, Gerrit Jasper ; Scheepens, Johannes Fredericus ; Scheringer, Martin ; Schiwy, Sabrina ; Schlottmann, Antje ; Schneider, Flurina ; Schulte, Lisa Maria ; Schulze-Sylvester, Maria ; Stelzer, Ernst H. K. ; Strobl, Frederic ; Sundermann, Andrea ; Tockner, Klement ; Tröger, Tobias ; Vilcinskas, Andreas ; Völker, Carolin ; Winkelmann, Ricarda ; Hollert, Henner
The Indian species of the genera Orionis Shaw and Stenothremma Shaw (Braconidae, Euphorinae) are reviewed. Both genera are reported for the first time from India. Three new species, Orionis shillongensis Gupta, van Achterberg & Pattar sp. nov. from north-eastern India (Meghalaya), O. femorator Gupta, van Achterberg & Pattar sp. nov. from southern India (Karnataka and Tamil Nadu) and Stenothremma flavator Gupta & van Achterberg sp. nov. from southern India (Karnataka) are illustrated and described. A key to the Old World species of Orionis Shaw is provided.