Development and implementation of natural killer cell simultaneous ADCC and direct killing assay

Assays to quantify natural killer (NK) cell killing efficacy have traditionally focused on assessing either direct killing or antibody dependent cell-mediated cytotoxicity (ADCC) independently. Due to the probability that immunotherapeutic interventions affect NK cell-mediated direct killing and NK cell-mediated ADCC differently, we developed an assay with the capacity to measure NK cell-mediated direct killing and ADCC simultaneously with cells from the same human donor. Specifically, this design allows for a single NK cell population to be split into several experimental conditions (e.g., direct killing, ADCC), thus controlling for potential confounders associated with human-to-human variation when assessing immunotherapy impacts. Our Natural Killer cell Simultaneous ADCC and Direct Killing Assay (NK-SADKA) allows researchers to reproducibly quantify both direct killing and ADCC by human NK cells. Furthermore, this optimized experimental design allows for concurrent analysis of the NK cells via flow cytometric immunophenotyping of NK cell populations which will facilitate the identification of relationships between NK cell phenotype and the subsequent killing potential. This assay will be valuable for assessing the broader impact(s) of immunotherapy strategies on both modes of NK cell killing

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Quantifying human natural killer cell-mediated direct killing of target cells

Peripheral blood mononuclear cells (PBMCs) include cells that are essential to the functions of the immune system, both in the innate and adaptive immune responses. Natural killer (NK) cells are a primary cell type responsible for executing innate responses. NK cells can recognize and kill infected or malignant cells without the need for memory functions or antigen specificity. However, NK cells can also destroy their targets using antibody-dependent cellular cytotoxicity, or ADCC (the topic of a separate presentation by fellow lab member, Cami Bisson). Direct killing requires only that target cells be recognized as “diseased” by the natural killer cells. Typically, this recognition is made based on target cells lacking expression of a normally present cell surface marker (i.e., MHC-I). Following the target cell recognition, NK cells initiate a cytotoxic response that lyses the target cell. Our lab has developed a testing system, referred to as the Natural Killer cell Simultaneous ADCC and Direct Killing Assay (NK-SADKA), that allows for the analysis of both ADCC and direct killing. The same donor samples are used for both the direct killing and ADCC portions of the assay to control for donor response variation. Within the direct killing portion of the assay (the focus of this presentation), MHC-I-deficient human leukemia cells (e.g., K562s) are labeled with a fluorescent dye to distinguish them from the unlabeled human NK effector cells. Target and effector cells are combined (5:1 effector to target ratio) and co-incubated (2 hours). Killing capacity is analyzed using a flow cytometer. Our direct killing arm of the NK-SADKA is functioning properly, as demonstrated by our data showing substantial killing following the coincubation relative to the viability of targets or effectors incubated alone. Data-to-date will be presented. Our NK-SADKA, including the direct killing arm described herein, will have impacts on clinical trial interpretations and designs, particularly when those trials are using interventions (e.g., immunotherapies) intended to alter NK cell killing capacities

Twelve-Month Outcomes of the AFFINITY Trial of Fluoxetine for Functional Recovery After Acute Stroke: AFFINITY Trial Steering Committee on Behalf of the AFFINITY Trial Collaboration

Background and Purpose: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. Methods: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. Results: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76–1.14]; P =0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P =0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P =0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P =0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P =0.64) at 12 months. Conclusions: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. REGISTRATION: URL: http://www.anzctr.org.au/ ; Unique identifier: ACTRN12611000774921

Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

none724siBackground The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally.Methods Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Data were assessed overall and by WHO regions, sex, and index versus non-index cases.Findings Of the 61 612 individuals in the registry, 42 167 adults (21 999 [53.6%] women) from 56 countries were included in the study. Of these, 31 798 (75.4%) were diagnosed with the Dutch Lipid Clinic Network criteria, and 35 490 (84.2%) were from the WHO region of Europe. Median age of participants at entry in the registry was 46.2 years (IQR 34.3-58.0); median age at diagnosis of familial hypercholesterolaemia was 44.4 years (32.5-56.5), with 40.2% of participants younger than 40 years when diagnosed. Prevalence of cardiovascular risk factors increased progressively with age and varied by WHO region. Prevalence of coronary disease was 17.4% (2.1% for stroke and 5.2% for peripheral artery disease), increasing with concentrations of untreated LDL cholesterol, and was about two times lower in women than in men. Among patients receiving lipid-lowering medications, 16 803 (81.1%) were receiving statins and 3691 (21.2%) were on combination therapy, with greater use of more potent lipid-lowering medication in men than in women. Median LDL cholesterol was 5.43 mmol/L (IQR 4.32-6.72) among patients not taking lipid-lowering medications and 4.23 mmol/L (3.20-5.66) among those taking them. Among patients taking lipid-lowering medications, 2.7% had LDL cholesterol lower than 1.8 mmol/L; the use of combination therapy, particularly with three drugs and with proprotein convertase subtilisin-kexin type 9 inhibitors, was associated with a higher proportion and greater odds of having LDL cholesterol lower than 1.8 mmol/L. Compared with index cases, patients who were non-index cases were younger, with lower LDL cholesterol and lower prevalence of cardiovascular risk factors and cardiovascular diseases (all p&lt;0.001).Interpretation Familial hypercholesterolaemia is diagnosed late. Guideline-recommended LDL cholesterol concentrations are infrequently achieved with single-drug therapy. Cardiovascular risk factors and presence of coronary disease were lower among non-index cases, who were diagnosed earlier. Earlier detection and greater use of combination therapies are required to reduce the global burden of familial hypercholesterolaemia. Copyright (C) 2021 Elsevier Ltd. All rights reserved.mixedVallejo-Vaz, Antonio J.; Stevens, Christophe A.T.; Lyons, Alexander R.M.; Dharmayat, Kanika I.; Freiberger, Tomas; Hovingh, G. 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David; März, Winfried; Mirrakhimov, Erkin; Miserez, André R.; Mitchenko, Olena; Nawawi, Hapizah; Nordestgaard, Børge G.; Panayiotou, Andrie G.; Paragh, György; Petrulioniene, Zaneta; Pojskic, Belma; Postadzhiyan, Arman; Raslova, Katarina; Reda, Ashraf; Reiner, Željko; Sadiq, Fouzia; Sadoh, Wilson Ehidiamen; Schunkert, Heribert; Shek, Aleksandr B.; Stoll, Mario; Stroes, Erik; Su, Ta-Chen; Subramaniam, Tavintharan; Susekov, Andrey V.; Tilney, Myra; Tomlinson, Brian; Truong, Thanh Huong; Tselepis, Alexandros D.; Tybjærg-Hansen, Anne; Vázquez Cárdenas, Alejandra; Viigimaa, Margus; Wang, Luya; Yamashita, Shizuya; Kastelein, John J.P.; Bruckert, Eric; Vohnout, Branislav; Schreier, Laura; Pang, Jing; Ebenbichler, Christoph; Dieplinger, Hans; Innerhofer, Reinhold; Winhofer-Stöckl, Yvonne; Greber-Platzer, Susanne; Krychtiuk, Konstantin; Speidl, Walter; Toplak, Hermann; Widhalm, Kurt; Stulnig, Thomas; Huber, Kurt; Höllerl, Florian; Rega-Kaun, Gersina; Kleemann, Lucas; Mäser, Martin; Scholl-Bürgi, Sabine; Säly, Christoph; Mayer, Florian J.; Sablon, Gaelle; Tarantino, Eric; Nzeyimana, Charlotte; Pojskic, Lamija; Sisic, Ibrahim; Nalbantic, Azra D.; Jannes, Cinthia E.; Pereira, Alexandre C.; Krieger, Jose E.; Petrov, Ivo; Goudev, Assen; Nikolov, Fedya; Tisheva, Snejana; Yotov, Yoto; Tzvetkov, Ivajlo; Baass, Alexis; Bergeron, Jean; Bernard, Sophie; Brisson, Diane; Brunham, Liam R.; Cermakova, Lubomira; Couture, Patrick; Francis, Gordon A.; Gaudet, Daniel; Hegele, Robert A.; Khoury, Etienne; Mancini, G.B. 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Ulrich; Klose, Gerald; König, Christel; Gouni-Berthold, Ioanna; Otte, Britta; Böll, Gereon; Kirschbaum, Anja; Merke, Jürgen; Scholl, Johannes; Segiet, Thomas; Gebauer, Marco; Predica, Florentina; Mayer, Manfred; Leistikow, Frank; Füllgraf-Horst, Sabine; Müller, Cornelius; Schüler, Melanie; Wiener, Judith; Hein, Konrad; Baumgartner, Peter; Kopf, Stefan; Busch, Reinhold; Schömig, Michael; Matthias, Stephan; Allendorf-Ostwald, Nicole; Fink, Bruno; Böhm, Dieter; Jäkel, Alexander; Koschker, Ann-Cathrin; Schweizer, Rüdiger; Vogt, Anja; Parhofer, Klaus; König, Wolfgang; Reinhard, Wibke; Bäßler, Andrea; Stadelmann, Alexander; Schrader, Volker; Katzmann, Julius; Tarr, Adrienne; Steinhagen-Thiessen, Elisabeth; Kassner, Ursula; Paulsen, Gerret; Homberger, Jürgen; Zemmrich, Claudia; Seeger, Wolfgang; Biolik, Kathrin; Deiss, Dorothee; Richter, Corinna; Pantchechnikova, Elina; Dorn, Elena; Schatz, Ulrike; Julius, Ulrich; Spens, Antje; Wiesner, Tobias; Scholl, Michael; Rizos, Christos V.; Sakkas, Nikolaos; Elisaf, Moses; Skoumas, Ioannis; Tziomalos, Konstantinos; Rallidis, Loukianos; Kotsis, Vasileios; Doumas, Michalis; Athyros, Vasileios; Skalidis, Emmanouil; Kolovou, Genovefa; Garoufi, Anastasia; Bilianou, Eleni; Koutagiar, Iosif; Agapakis, Dimitrios; Kiouri, Estela; Antza, Christina; Katsiki, Niki; Zacharis, Evangelos; Attilakos, Achilleas; Sfikas, George; Koumaras, Charalambos; Anagnostis, Panagiotis; Anastasiou, Georgia; Liamis, George; Koutsogianni, Amalia-Despoina; Karányi, Zsolt; Harangi, Mariann; Bajnok, László; Audikovszky, Mária; Márk, László; Benczúr, Béla; Reiber, István; Nagy, Gergely; Nagy, András; Reddy, Lakshmi L.; Shah, Swarup A.V.; Ponde, Chandrashekhar K.; Dalal, Jamshed J.; Sawhney, Jitendra P.S.; Verma, Ishwar C.; Altaey, Mays; Al-Jumaily, Khalid; Rasul, Dilshad; Abdalsahib, Ali F.; Jabbar, Amer A.; Al-ageedi, Mohanad; Agar, Ruth; Cohen, Hofit; Ellis, Avishay; Gavishv, Dov; Harats, Dror; Henkin, Yaacov; Knobler, Hila; Leavit, Leah; Leitersdorf, Eran; Rubinstein, Ardon; Schurr, Daniel; Shpitzen, Shoshi; Szalat, Auryan; Casula, Manuela; Zampoleri, Veronica; Gazzotti, Marta; Olmastroni, Elena; Sarzani, Riccardo; Ferri, Claudio; Repetti, Elena; Sabbà, Carlo; Bossi, Antonio Carlo; Borghi, Claudio; Muntoni, Sandro; Cipollone, Francesco; Purrello, Francesco; Pujia, Arturo; Passaro, Angelina; Marcucci, Rossella; Pecchioli, Valerio; Pisciotta, Livia; Mandraffino, Giuseppe; Pellegatta, Fabio; Mombelli, Giuliana; Branchi, Adriana; Fiorenza, Anna Maria; Pederiva, Cristina; Werba, Josè Pablo; Parati, Gianfranco; Carubbi, Francesca; Iughetti, Lorenzo; Iannuzzi, Arcangelo; Iannuzzo, Gabriella; Calabrò, Paolo; Averna, Maurizio; Biasucci, Giacomo; Zambon, Sabina; Roscini, Anna Rita; Trenti, Chiara; Arca, Marcello; Federici, Massimo; Del Ben, Maria; Bartuli, Andrea; Giaccari, Andrea; Pipolo, Antonio; Citroni, Nadia; Guardamagna, Ornella; Bonomo, Katia; Benso, Andrea; Biolo, Gianni; Maroni, Lorenzo; Lupi, Alessandro; Bonanni, Luca; Zenti, Maria Grazia; Matsuki, Kota; Hori, Mika; Ogura, Masatsune; Masuda, Daisaku; Kobayashi, Takuya; Nagahama, Kumiko; Al-Jarallah, Mohammed; Radovic, Mirjana; Lunegova, Olga; Bektasheva, Erkayim; Khodzhiboboev, Elyor; Erglis, Andrejs; Gilis, Dainus; Nesterovics, Georgijs; Saripo, Vita; Meiere, Ruta; Upena-RozeMicena, Arta; Terauda, Elizabete; Jambart, Selim; Khoury, Petra E.; Elbitar, Sandy; Ayoub, Carine; Ghaleb, Youmna; Aliosaitiene, Urte; Kutkiene, Sandra; Kasim, Noor A.M.; Nor, Noor S.M.; Ramli, Anis S.; Razak, Suraya A.; Al-Khateeb, Alyaa; Kadir, Siti H.S.A.; Muid, Suhaila A.; Rahman, Thuhairah A.; Kasim, Sazzli S.; Radzi, Ahmad B.M.; Ibrahim, Khairul S.; Razali, Salmi; Ismail, Zaliha; Ghani, Rohana A.; Hafidz, Muhammad I.A.; Chua, Ang L.; Rosli, Marshima M.; Annamalai, Muthukkaruppan; Teh, Lay K.; Razali, Rafezah; Chua, Yung A.; Rosman, Azhari; Sanusi, Abdul R.; Murad, Nor A.A.; Jamal, A. Rahman A.; Nazli, Sukma A.; Razman, Aimi Z.; Rosman, Norhidayah; Rahmat, Radzi; Hamzan, Nur S.; Azzopardi, C.; Mehta, Roopa; Martagon, Alexandro J.; Ramirez, Gabriela A.G.; Villa, Neftali E.A.; Vazquez, Arsenio V.; Elias-Lopez, Daniel; Retana, Gustavo G.; Rodriguez, Betsabel; Macías, Jose J.C.; Zazueta, Alejandro R.; Alvarado, Rocio M.; Portano, Julieta D.M.; Lopez, Humberto A.; Sauque-Reyna, Leobardo; Herrera, Laura G.G.; Mendia, Luis E.S.; Aguilar, Humberto Garcia; Cooremans, Elizabeth R.; Aparicio, Berenice P.; Zubieta, Victoria M.; Gonzalez, Perla A.C.; Ferreira-Hermosillo, Aldo; Portilla, Nacu C.; Dominguez, Guadalupe J.; Garcia, Alinna Y.R.; Cazares, Hector E.A.; Gonzalez, Jesus R.; Valencia, Carla V.M.; Padilla, Francisco G.; Prado, Ramon M.; De los Rios Ibarra, Manuel O.; Villicaña, Ruy D.A.; Rivera, Karina J.A.; Carrera, Ricardo A.; Alvarez, Jose A.; Martinez, Jose C.A.; de los Reyes Barrera Bustillo, Manuel; Vargas, Gonzalo C.; Chacon, Roberto C.; Andrade, Mario H.F.; Ortega, Ashanty F.; Alcala, Hector G.; de Leon, Laura E.G.; Guzman, Berenice G.; Garcia, Jose J.G.; Cuellar, Juan C.G.; Cruz, Jose R.G.; Garcia, Anell Hernandez; Almada, Jesus R.H.; Herrera, Ursulo J.; Sobrevilla, Fabiola L.; Rodriguez, Eduardo M.; Sibaja, Cristina M.; Rodriguez, Alma B.M.; Oyervides, Jose C.M.; Vazquez, Daniel I.P.; Rodriguez, Eduardo A.R.; Osorio, Ma L.R.; Saucedo, Juan R.; Tamayo, Margarita T.; Talavera, Luis A.V.; Arroyo, Luis E.V.; Carrillo, Eloy A.Z.; Isara, Alphonsus; Obaseki, Darlington E.; Al-Waili, Khalid; Al-Zadjali, Fahad; Al-Zakwani, Ibrahim; Al-Kindi, Mohammed; Al-Mukhaini, Suad; Al-Barwani, Hamida; Rana, Asim; Shah, Lahore S.U.; Starostecka, Ewa; Konopka, Agnieszka; Lewek, Joanna; Bartłomiejczyk, Marcin; Gąsior, Mariusz; Dyrbuś, Krzysztof; Jóźwiak, Jacek; Gruchała, Marcin; Pajkowski, Marcin; Romanowska-Kocejko, Marzena; Żarczyńska-Buchowiecka, Marta; Chmara, Magdalena; Wasąg, Bartosz; Parczewska, Aleksandra; Gilis-Malinowska, Natasza; Borowiec-Wolna, Justyna; Stróżyk, Aneta; Woś, Marlena; Michalska-Grzonkowska, Aleksandra; Medeiros, Ana M.; Alves, Ana C.; Silva, Francisco; Lobarinhas, Goreti; Palma, Isabel; de Moura, Jose P.; Rico, Miguel T.; Rato, Quitéria; Pais, Patrícia; Correia, Susana; Moldovan, Oana; Virtuoso, Maria J.; Salgado, Jose M.; Colaço, Ines; Dumitrescu, Andreea; Lengher, Calin; Mosteoru, Svetlana; Meshkov, Alexey; Ershova, Alexandra; Rozkova, Tatiana; Korneva, Victoria; Yu, Kuznetsova T.; Zafiraki, Vitaliy; Voevoda, Mikhail; Gurevich, Victor; Duplyakov, Dmitry; Ragino, Yulia; Safarova, Maya; Shaposhnik, Igor; Alkaf, Fahmi; Khudari, Alia; Rwaili, Nawal; Al-Allaf, Faisal; Alghamdi, Mohammad; Batais, Mohammed A.; Almigbal, Turky H.; Kinsara, Abdulhalim; AlQudaimi, Ashraf H.A.; Awan, Zuhier; Elamin, Omer A.; Altaradi, Hani; Rajkovic, Natasa; Popovic, Ljiljana; Singh, Sandra; Stosic, Ljubica; Rasulic, Iva; Lalic, Nebojsa M.; Lam, Carolyn; Le, Tan J.; Siang, Eric L.T.; Dissanayake, Sanjaya; I-Shing, Justin T.; Shyong, Tai E.; Jin, Terrance C.S.; Balinth, Karin; Buganova, Ingrid; Fabryova, Lubomira; Kadurova, Michaela; Klabnik, Alexander; Kozárová, Miriam; Sirotiakova, Jana; Battelino, Tadej; Kovac, Jernej; Mlinaric, Matej; Sustar, Ursa; Podkrajsek, Katarina T.; Fras, Zlatko; Jug, Borut; Cevc, Matija; Pilcher, Gillian J.; Blom, D.J.; Wolmarans, K.H.; Brice, B.C.; Muñiz-Grijalvo, Ovidio; Díaz-Díaz, Jose L.; de Isla, Leopoldo P.; Fuentes, Francisco; Badimon, Lina; Martin, François; Lux, Angela; Chang, Nien-Tzu; Ganokroj, Poranee; Akbulut, Mehmet; Alici, Gökhan; Bayram, Fahri; Can, Levent H.; Celik, Ahmet; Ceyhan, Ceyhun; Coskun, Fatma Y.; Demir, Mesut; Demircan, Sabri; Dogan, Volkan; Durakoglugil, Emre; Dural, Ibrahim E.; Gedikli, Omer; Hacioglu, Aysa; Ildizli, Muge; Kilic, Salih; Kirilmaz, Bahadir; Kutlu, Merih; Oguz, Aytekin; Ozdogan, Oner; Onrat, Ersel; Ozer, Savas; Sabuncu, Tevfik; Sahin, Tayfun; Sivri, Fatih; Sonmez, Alper; Temizhan, Ahmet; Topcu, Selim; Tuncez, Abdullah; Vural, Mirac; Yenercag, Mustafa; Yesilbursa, Dilek; Yigit, Zerrin; Yildirim, Aytul B.; Yildirir, Aylin; Yilmaz, Mehmet B.; Atallah, Bassam; Traina, Mahmoud; Sabbour, Hani; Hay, Dana A.; Luqman, Neama; Elfatih, Abubaker; Abdulrasheed, Arshad; Kwok, See; Oca, Nicolas D.; Reyes, Ximena; Alieva, Rano B.; Kurbanov, Ravshanbek D.; Hoshimov, Shavkat U.; Nizamov, Ulugbek I.; Ziyaeva, Adolat V.; Abdullaeva, Guzal J.; Do, Doan L.; Nguyen, Mai N.T.; Kim, Ngoc T.; Le, Thanh T.; Le, Hong A.; Tokgozoglu, Lale; Catapano, Alberico L.; Ray, Kausik K.Vallejo-Vaz, Antonio J.; Stevens, Christophe A. T.; Lyons, Alexander R. M.; Dharmayat, Kanika I.; Freiberger, Tomas; Hovingh, G. Kees; Mata, Pedro; Raal, Frederick J.; Santos, Raul D.; Soran, Handrean; Watts, Gerald F.; Abifadel, Marianne; Aguilar-Salinas, Carlos A.; Alhabib, Khalid F.; Alkhnifsawi, Mutaz; Almahmeed, Wael; Alnouri, Fahad; Alonso, Rodrigo; Al-Rasadi, Khalid; Al-Sarraf, Ahmad; Al-Sayed, Nasreen; Araujo, Francisco; Ashavaid, Tester F.; Banach, Maciej; Béliard, Sophie; Benn, Marianne; Binder, Christoph J.; Bogsrud, Martin P.; Bourbon, Mafalda; Chlebus, Krzysztof; Corral, Pablo; Davletov, Kairat; Descamps, Olivier S.; Durst, Ronen; Ezhov, Marat; Gaita, Dan; Genest, Jacques; Groselj, Urh; Harada-Shiba, Mariko; Holven, Kirsten B.; Kayikcioglu, Meral; Khovidhunkit, Weerapan; Lalic, Katarina; Latkovskis, Gustavs; Laufs, Ulrich; Liberopoulos, Evangelos; Lima-Martinez, Marcos M.; Lin, Jie; Maher, Vincent; Marais, A. David; März, Winfried; Mirrakhimov, Erkin; Miserez, André R.; Mitchenko, Olena; Nawawi, Hapizah; Nordestgaard, Børge G.; Panayiotou, Andrie G.; Paragh, György; Petrulioniene, Zaneta; Pojskic, Belma; Postadzhiyan, Arman; Raslova, Katarina; Reda, Ashraf; Reiner, Željko; Sadiq, Fouzia; Sadoh, Wilson Ehidiamen; Schunkert, Heribert; Shek, Aleksandr B.; Stoll, Mario; Stroes, Erik; Su, Ta-Chen; Subramaniam, Tavintharan; Susekov, Andrey V.; Tilney, Myra; Tomlinson, Brian; Truong, Thanh Huong; Tselepis, Alexandros D.; Tybjærg-Hansen, Anne; Vázquez Cárdenas, Alejandra; Viigimaa, Margus; Wang, Luya; Yamashita, Shizuya; Kastelein, John J. P.; Bruckert, Eric; Vohnout, Branislav; Schreier, Laura; Pang, Jing; Ebenbichler, Christoph; Dieplinger, Hans; Innerhofer, Reinhold; Winhofer-Stöckl, Yvonne; Greber-Platzer, Susanne; Krychtiuk, Konstantin; Speidl, Walter; Toplak, Hermann; Widhalm, Kurt; Stulnig, Thomas; Huber, Kurt; Höllerl, Florian; Rega-Kaun, Gersina; Kleemann, Lucas; Mäser, Martin; Scholl-Bürgi, Sabine; Säly, Christoph; Mayer, Florian J.; Sablon, Gaelle; Tarantino, Eric; Nzeyimana, Charlotte; Pojskic, Lamija; Sisic, Ibrahim; Nalbantic, Azra D.; Jannes, Cinthia E.; Pereira, Alexandre C.; Krieger, Jose E.; Petrov, Ivo; Goudev, Assen; Nikolov, Fedya; Tisheva, Snejana; Yotov, Yoto; Tzvetkov, Ivajlo; Baass, Alexis; Bergeron, Jean; Bernard, Sophie; Brisson, Diane; Brunham, Liam R.; Cermakova, Lubomira; Couture, Patrick; Francis, Gordon A.; Gaudet, Daniel; Hegele, Robert A.; Khoury, Etienne; Mancini, G. B. John; Mccrindle, Brian W.; Paquette, Martine; Ruel, Isabelle; Cuevas, Ada; Asenjo, Sylvia; Wang, Xumin; Meng, Kang; Song, Xiantao; Yong, Qiang; Jiang, Tao; Liu, Ziyou; Duan, Yanyu; Hong, Jing; Ye, Pucong; Chen, Yan; Qi, Jianguang; Liu, Zesen; Li, Yuntao; Zhang, Chaoyi; Peng, Jie; Yang, Ya; Yu, Wei; Wang, Qian; Yuan, Hui; Cheng, Shitong; Jiang, Long; Chong, Mei; Jiao, Jian; Wu, Yue; Wen, Wenhui; Xu, Liyuan; Zhang, Ruiying; Qu, Yichen; He, Jianxun; Fan, Xuesong; Wang, Zhenjia; Chow, Elaine; Pećin, Ivan; Perica, Dražen; Symeonides, Phivos; Vrablik, Michal; Ceska, Richard; Soska, Vladimir; Tichy, Lukas; Adamkova, Vera; Franekova, Jana; Cifkova, Renata; Kraml, Pavel; Vonaskova, Katerina; Cepova, Jana; Dusejovska, Magdalena; Pavlickova, Lenka; Blaha, Vladimir; Rosolova, Hana; Nussbaumerova, Barbora; Cibulka, Roman; Vaverkova, Helena; Cibickova, Lubica; Krejsova, Zdenka; Rehouskova, Katerina; Malina, Pavel; Budikova, Milena; Palanova, Vaclava; Solcova, Lucie; Lubasova, Alena; Podzimkova, Helena; Bujdak, Juraj; Vesely, Jiri; Jordanova, Marta; Salek, Tomas; Urbanek, Robin; Zemek, Stanislav; Lacko, Jan; Halamkova, Hana; Machacova, Sona; Mala, Sarka; Cubova, Eva; Valoskova, Katerina; Burda, Lukas; Bendary, Ahmed; Daoud, Ihab; Emil, Sameh; Elbahry, Atef; Rafla, Samir; Sanad, Osama; Kazamel, Ghada; Ashraf, Mohamed; Sobhy, Mohamed; El-Hadidy, Amro; Shafy, Mohamed A.; Kamal, Saif; Bendary, Mohamed; Talviste, Grete; Angoulvant, Denis; Boccara, Franck; Cariou, Bertrand; Carreau, Valérie; Carrie, Alain; Charrieres, Sybil; Cottin, Yves; Di-Fillipo, Mathilde; Ducluzeau, Pierre H.; Dulong, Sonia; Durlach, Vincent; Farnier, Michel; Ferrari, Emile; Ferrieres, Dorota; Ferrieres, Jean; Gallo, Antonio; Hankard, Regis; Inamo, Jocelyne; Lemale, Julie; Moulin, Philippe; Paillard, François; Peretti, Noel; Perrin, Agnès; Pradignac, Alain; Rabes, Jean P.; Rigalleau, Vincent; Sultan, Ariane; Schiele, François; Tounian, Patrick; Valero, René; Verges, Bruno; Yelnik, Cécile; Ziegler, Olivier; Haack, Ira A.; Schmidt, Nina; Dressel, Alexander; Klein, Isabel; Christmann, Jutta; Sonntag, Antonia; Stumpp, Christine; Boger, Diana; Biedermann, Dana; Usme, Monica M. N.; Beil, F. Ulrich; Klose, Gerald; König, Christel; Gouni-Berthold, Ioanna; Otte, Britta; Böll, Gereon; Kirschbaum, Anja; Merke, Jürgen; Scholl, Johannes; Segiet, Thomas; Gebauer, Marco; Predica, Florentina; Mayer, Manfred; Leistikow, Frank; Füllgraf-Horst, Sabine; Müller, Cornelius; Schüler, Melanie; Wiener, Judith; Hein, Konrad; Baumgartner, Peter; Kopf, Stefan; Busch, Reinhold; Schömig, Michael; Matthias, Stephan; Allendorf-Ostwald, Nicole; Fink, Bruno; Böhm, Dieter; Jäkel, Alexander; Koschker, Ann-Cathrin; Schweizer, Rüdiger; Vogt, Anja; Parhofer, Klaus; König, Wolfgang; Reinhard, Wibke; Bäßler, Andrea; Stadelmann, Alexander; Schrader, Volker; Katzmann, Julius; Tarr, Adrienne; Steinhagen-Thiessen, Elisabeth; Kassner, Ursula; Paulsen, Gerret; Homberger, Jürgen; Zemmrich, Claudia; Seeger, Wolfgang; Biolik, Kathrin; Deiss, Dorothee; Richter, Corinna; Pantchechnikova, Elina; Dorn, Elena; Schatz, Ulrike; Julius, Ulrich; Spens, Antje; Wiesner, Tobias; Scholl, Michael; Rizos, Christos V.; Sakkas, Nikolaos; Elisaf, Moses; Skoumas, Ioannis; Tziomalos, Konstantinos; Rallidis, Loukianos; Kotsis, Vasileios; Doumas, Michalis; Athyros, Vasileios; Skalidis, Emmanouil; Kolovou, Genovefa; Garoufi, Anastasi