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101. Global plasma protein profiling reveals DCM characteristic protein signatures

Author

Matthias Nauck, Cristina Pop, Kerstin Weitmann, Sabine Ameling, Daniel Beug, Praveen K. Sappa, Stephan B. Felix, Marcus Dörr, Elke Hammer, Heinz-Peter Schultheiss, Uwe Völker, Martin Andreas Feig, Uwe Kühl, K Lehnert, and Gourav Bhardwaj

Subjects
0301 basic medicine, Cardiomyopathy, Dilated, Male, Proteomics, medicine.medical_specialty, Myocarditis, Apolipoprotein B, Biophysics, Biochemistry, Mass Spectrometry, 03 medical and health sciences, Plasma, Internal medicine, medicine, Humans, cardiovascular diseases, Blood Coagulation, Inflammation, Ejection fraction, 030102 biochemistry & molecular biology, biology, business.industry, Aryldialkylphosphatase, Gene Expression Profiling, Acute-phase protein, Dilated cardiomyopathy, Stroke Volume, Middle Aged, medicine.disease, Lipid Metabolism, PON1, Blood proteins, 030104 developmental biology, Cystatin C, biology.protein, Cardiology, Female, business, Biomarkers, Acute-Phase Proteins
Abstract

To identify potential biomarkers supporting better phenotyping and to improve understanding of the pathophysiology of dilated cardiomyopathy (DCM), this study comparatively analyzed plasma protein profiles of DCM patients and individuals with low normal and normal left ventricular ejection fraction (LVEF) by mass spectrometry. After plasma depletion using a MARS Hu-6 column, global proteome profiling was performed using a LTQ-Orbitrap Velos mass spectrometer. To compare and confirm results, two different discovery sets of samples were investigated. Differentially abundant proteins are involved in lipid metabolism, coagulation, and acute phase response. Serum paraoxonase 1 (PON1), cystatin C, lysozyme C, apolipoprotein A-II, and apolipoprotein M were validated by targeted protein analysis in a third independent patient cohort. Additionally, PON1 levels were also determined by an ELISA. These data highlight PON1 as a potential marker for differentiating DCM patients not only from patients with normal LVEF, but also from heart failure patients with preserved ejection fraction. The results highlight lipid metabolism and inflammation as the major pathways being altered in DCM patients in comparison to patients presenting with suspicious myocarditis to the hospital. Significance Several studies focused on the identification of heart failure (HF) associated protein signatures in blood plasma, but only few that are largely based on only small sample series considered specific HF pathologies. Therefore, we performed a comparative global blood plasma protein profiling of a larger sample of individuals with reduced left ventricular ejection fraction (LVEF) classified as dilated cardiomyopathy patients and individuals with normal LVEF but presenting with suspicious myocarditis. DCM patients displayed altered levels of proteins involved in lipid metabolism, coagulation, and acute phase response. The most reliable candidates, such as serum paraoxonase 1 (PON1), cystatin C, lysozyme C, apolipoprotein A-II, and apolipoprotein M were validated by targeted protein analysis in an independent patient cohort. PON1 levels were also determined by an ELISA. These data highlight PON1 as a potential marker for differentiating DCM patients not only from patients with normal LVEF, but also from heart failure patients with preserved ejection fraction.

Published
2019

102. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial

Author

Hertzel C Gerstein, Helen M Colhoun, Gilles R Dagenais, Rafael Diaz, Mark Lakshmanan, Prem Pais, Jeffrey Probstfield, Fady T Botros, Matthew C Riddle, Lars Rydén, Denis Xavier, Charles Messan Atisso, Leanne Dyal, Stephanie Hall, Purnima Rao-Melacini, Gloria Wong, Alvaro Avezum, Jan Basile, Namsik Chung, Ignacio Conget, William C Cushman, Edward Franek, Nicolae Hancu, Markolf Hanefeld, Shaun Holt, Petr Jansky, Matyas Keltai, Fernando Lanas, Lawrence A Leiter, Patricio Lopez-Jaramillo, Ernesto German Cardona Munoz, Valdis Pirags, Nana Pogosova, Peter J Raubenheimer, Jonathan E Shaw, Wayne H-H Sheu, Theodora Temelkova-Kurktschiev, Mercedes Abella, Andrea Alebuena, Sandra Almagro, Eduardo Amoroso, Paula Anadon, Elizabeth Andreu, Guillermo Aristimuño, Maria Arzadun, Maria Barbieri, Raul Barcudi, Ines Bartolacci, Gabriel Bolobanich, Anselmo Bordonava, Miguel Bustamante Labarta, Betina Bustos, Alberto Caccavo, Alejandra Camino, Maria Cantero, Maria Carignano, Luis Cartasegna, Marcela Cipullo, Víctor Commendatore, Victoria Conosciuto, Osvaldo Costamagna, Claudia Crespo, Jose Cuello, Carlos Cuneo, Sandra Cusimano, Sofia Dean, Claudio Dituro, Andrea Dominguez, Miguel Farah, Alberto Fernandez, Florencia Fernandez, Adriana Ferrari, Patricia Flammia, Jose Fuentealba, Karina Beatriz Gallardo, Celso Garcia, Ruben Garcia Duran, Marcelo Garrido, Rodolfo Gavicola, Claudio Gerbaudo, Graciela Gilli, Ana Paula Giotto, Pedro Godoy Bolzán, Oscar Gomez Vilamajo, Fernando Guerlloy, Cristian Guridi, Narcisa Gutierrez Garrido, Eduardo Hasbani, Sonia Hermida, Miguel Hominal, Adrian Hrabar, Adrián Ingaramo, Alejandra Izzicupo, Mario Krynski, Mariana Lagrutta, Paulina Lanchiotti, Maria Langhe, Veronica Leonard, Javier Llanos, Ricardo Lopez Santi, Jorge Lowenstein, Cecilia Luquez, Ignacio Mackinnon, Melina Mana, Sara Manzur, Javier Marino, Carolina Martella, Roger Martinez, Re Matias, Javier Matkovich, Monica Meritano, Oscar Montaña, María Mulazzi, Juan Ochoa, Gustavo Paterlini, María Pelagagge, Maria Elena Peralta Lopez, Aldo Prado, Lorena Pruyas, Martín Racca, Carola Ricotti, Carolina Rodriguez, Mariano Romero Vidomlansky, Ricardo Ronderos, Ana Laura Sadowski, Jorgelina Sala, Alejandro Sánchez, Andrea Santoro, Lilia Schiavi, Mariano Sein, Virginia Sernia, Leonardo Serra, Maximiliano Sicer, Tomas Smith, Leonardo Soso, Georgina Sposetti, Andrea Steinacher, Jorge Stival, Jorge Tedesco, Hugo Tonin, Mauro Tortolo, Maria Ulla, Julio Vallejos, Marisa Vico, Luciana Virgillito, Virginia Visco, Daniel Vogel, Florencia Waisman, César Zaidman, Noemi Zucchiatti, Imran Badshah, Neale Cohen, Peter Colman, David Colquhoun, Timothy Davis, Spiros Fourlanos, Greg Fulcher, Jane Hamlyn, Cilla Haywood, Samantha Hocking, Maeve Huchinson, William Jeffries, Mervyn Kyl, Clement Lo, PeakMann Mah, Ashley Makepeace, Dolly Marope, Natalie Nanayakkar, Alison Nankervis, Neil Palmer, Barbara Palolus, Satish Pillai, Sarah Price, Joseph Proietto, Anne Reutens, Natassia Rodrigo, Abdul Sheikh, Greg Smith, Michelle So, Georgia Soldatos, Bronwyn Stuckey, Priya Sumithran, Helena Teede, Parind Vora, Lyn Williams, Eduardo Abib, Christiani Adão Poço, Érica Ferreira Alves, Janaina Andreatta Bernardi Barea, Livia Avezum Oliveira, Denise Ludovico da Costa de Castro, Ivan Correa da Cruz, Midiã Costa, Ivan Cruz, Sidney Cunha, Marco Antonio Vieira Da Silva, Renata de Carvalho Camara Bona, Bruna de Paula, Freddy Eliaschewitz, Guilherme Fazolli, Carlos Alberto Ferreira Filho, Jose Fortes, Cesar França, Denise Reis Franco, Paulo Roberto Genestreti, Flavio Giorgeto, Rodrigo Marques Gonçalves, Michele Elka Grossman, Ana Claudia Henrique Marcelino, Mauro Hernandes, Ana Horta, Cristiano Jaeger, Midia Kaneblai, Cecilia Kauffman Rutenberg, Jose Francisco Kerr Saraiva, Maria Angelica Lemos, Lilia Maia, Euler Roberto Manenti, Mariana Marques, Cynthia Melissa Valerio, Rodrigo Moreira, Flávia Mothé, Osana Maria Mouco, Philip Moura, José Carlos Moura Jorge, Carlos Nakashima, Marcelo Nakazone, Thiago Napoli, Cristiane Nunes, Joao Eduardo Nunes Salles, Karla Oliveira, Marcela Oliveira, Gracielly de Souza Pantano, Fabio Petri, Leonardo Piazza, Andreia Carla Pires, Patricia Pizzato, Sergio Prata, Dalton Precoma, Rafael Rech, Gilmar Reis, Heleno Reis, Elisabete Resende, Jose Ribas Fortes, Sylka Rodovalho, Fabio Rossi dos Santos, Joao Eduardo Salles, Célia Regina Sampaio, Thiago Santos, Vanessa Santos dos Santos, Tulio Silva e Quadros, Daniel Silveira, Katia Nunes Siqueira, M Teireira, Marcelo Uehara, C Valerio, Henrique Vianna, Maria Helena Vidotti, Guilherme de Lima Visconti, Maria Teresa Zanella, Viktoriya Andreeva, Radoslav Borisov, Nikolay Botushanov, Georgi Dimitrov, Kameliya Dimova, Tsvetan Dragoychev, Valentina Grigorova, Valentina Gushterova, Ivaylo Ivanov, Tatyana Kocelova, Dimo Kurktschiev, Milena Miletieva, Neli Nenkova-Gugusheva, Ralitsa Pancheva, Maria Pavlova, Dimitar Raev, Vesela Spasova, Anastas Stoikov, Dimitar Troev, Todor Yanev, Mariana Yoncheva-Mihaylova, Alexander Abitbol, Buki Ajala, Abdullh Alguwaihes, Jean-Luc Ardilouze, Nahla Aris-Jilwan, Amel Arnaout, Ronnie Aronson, Nadeem Aslam, Sandra Babin, Jean-Patrice Bailargeon, Allan Bailey, Harpreet Bajaj, Christian Beauchesne, Sorin Beca, Andre Belanger, Alan Bell, Diego Bellabarba, Lori Berard, Brian Berenbaum, Vincent Bergeron, Joseph Berlingieri, Frédéric Bernier, Phoebe Bishara, David Blank, Ian Blumer, Suzanne Brault, Donald Breton, André Carpentier, James Cha, Prakash Chandra, Jean-Louis Chiasson, James R Conway, Ghyslaine Couture, Nathalie Couture, Gilles Dagenais, Dyotirmoy Datta, Giuseppe D'Ignazio, Richard Dumas, Didier Fay, Andre Frechette, Louise Frenette, Daisy Fung, Nathalie Gagnon, Meri Galter, Jean Garon, Jean Sebastien Gauthier, Christian Geadah, Jeremy Gilbert, Ronald Girard, Ronald Goldenberg, Loren David Grossman, Nikhil Gupta, Jean-Pierre Halle, Marie-France Hivert, Ghislaine Houde, Robyn Houlden, Irene Hramiak, Ted Jablonski, Akshay Jain Jain, Hasnain Khandwala, Munish Khosla, C Lachance, Emilie Laflamme, Marie-France Langlois, Luc Larivee, Joanne Liutkus, Heather Lochnan, Saleem Malik, Charlotte McDonald, Pravinsagar Mehta, John Mihailidis, Alain Milot, Priya Narula, Patrice Nault, Arun Nayar, William Nisker, Gilles Ouellet, Jean Palardy, Minta Patel, Terri Paul, Sue Pedersen, Patrice Perron, Marie-Hélène Pesant, Paul Poirier, Marie-Claude Poulin, Zubin Punthakee, Waheed Rehman, Stuart Ross, P Sagar, Nouhad Saliba, Sam Sandler, Alicia Schiffrin, Robert Schlosser, Anila Seth-Sharma, Mark Sherman, David Sionit, Tharsan Sivakumar, Juan Soto, Eric St-Amour, Oren Steen, Jack Sussman, Adam Telner, Sheldon Tobe, David-Yaw Twum-Barima, Audrey Van Zanten, Nicole VanRossum, Jonathan Vecchiarelli, Rick Ward, John Wessengel, Stanley Weisnagel, Igor Wilderman, Vincent Woo, Natalia Yakubovich, Jean-Francois Yale, Zeina Yared, Monica Acevedo, Maria Loreto Aguirre, Andres Aizman, Maria Soledad Barroso, Leonardo Cobos, Alfredo Danin Vargas, Barbara Descalzi, Gonzalo Godoy, Elio Grumberg, Rodolfo Lahsen, Gladys Larenas, Eugenia Ortiz, Javier Paredes, Sergio Potthoff, Eva Retamal, Luis Rojas, Manuel Salgado, Claudio Santibanez, Carmen Solis, Benjamin Stokins, Jose Accini, Javier Acebedo, Lina Maria Agudelo Baena, Soraya Alarcon, Juliana Angel, Edgar Arcos, M Aroca Martinez, Leonor Atuesta, Jose Balaguera, Doris Ballestas, Sandra Isabel Barrera, Rosmy Barrios Reyes, Adolfo Bayona, Andres Bermudez, Diego Zarate Bernal, Marco Blanquicett, Victor Bravo, Wendy Bueno, Alvaro Burbano Delgado, Alberto Cadena, Andres Cadena, Sandra Caicedo, Carlos Celemin, Ricardo Consuegra, Cristhian Contreras Pimienta, Kelly Johenis Corredor, Carlos Cure, Lizeth Dayana De La Hoz Rueda, Erika Delgado, Sarahy Diaz, Marta Diego, Anabell Donado, William Encinales Sanabria, Juliana Escobar, Gillian Escorcia, Leonardo Forero, Laura Fuentes, Maria Garcia, Henry Garcia Lozada, Luis Garcia Ortiz, Angela Giraldo, Laura Gomez Gonzalez, Javier Granada, Corina Gutierrez, Natalia Henao, Edwin Hernandez, Olga Maria Herrera Uejbe, Juan Diego Higuera Cobos, Jaime Ibarra Gómez, Edwin Hernandez Jaimes, Monica Jaramillo, Nicolas Jaramillo, Carlos Jaramillo Gomez, Monica Jaramillo Sanchez, Ivonne Jarava Durán, Catalina Lopez Ceballos, Claudia Madrid, Elias María Amastha, Jennifer Mercado, Dora Ines Molina, Jessica Molina Soto, Carlos Montoya, Alexander Morales, Carolina Muñoz, Luis Alejandro Orozco, Oscar Osorio, Jorge Mario Palmera Sanchez, Adwar Peña, Jose Perez, Juan Perez Agudelo, Germán Pérez Amador, Carlos Pertuz, Irina Posada, Carlos Puerta, Adalberto Quintero, Diana Quiroz, Carmen Rendon, Alberto Reyes, Alvaro Reyes, Diana Ripoll, Carlos Rivera, Maria Rocha, Jose F Rodriguez, Kervis Asid Rodriguez Villanueva, Javier Emilio Rodriguez Zabala, Sindy Rojas, Maria Romero, Ricardo Rosero, Angelica Rocio Rosillo Cardenas, Lina Rueda, Gregorio Sanchez, Tatiana Sanchez, Arístides Sotomayor Herazo, Monica Suarez, Mariana Torres, Freddy Trujillo, Miguel Urina, Lazaro Van Strahlen, Carlos Velandia, Carolina Velasquez Guzman, Elizabeth Velazquez, Tatiana Vidal Prada, Juan Pablo Yepez Alvaran, Diego Zarate, Jana Andelova, Radka Benesova, Barbara Buzova, Vladimir Cech, Ida Chodova, Miroslav Choura, Antonin Dufka, Andrea Gamova, Jakub Gorgol, Tomas Hala, Hana Havlova, Dagmar Hlavkova, Petra Horanska, Juliana Ilcisin-Valova, Petra Jenickova, Ondrej Jerabek, Ilona Kantorova, Katerina Kolomaznikova, Iva Kopeckova, Miroslava Kopeckova, Karel Linhart, Tomas Linhart, Jan Malecha, Emilia Malicherova, Dana Neubauerova, Martina Oznerova, Radan Partys, Eva Pederzoliova, Maria Petrusova, Vera Prymkova, Eva Racicka, Ida Reissova, Eva Roderova, Libor Stanek, Alena Striova, Dana Svarcova, Petr Svoboda, Emilia Szeghy Malicharova, Jan Urge, Ladislav Vesely, Bedich Wasserburger, Hilde Wasserburgerova, Emil Zahumensky, Vaclav Zamrazil, Hasan Alawi, Ernestos Anastasiadis, Elisabeth Axthelm, Tasso Bieler, Christina Buhrig, Elizaveta Degtyareva, Frank Dellanna, Karl-Michael Derwahl, Stephan Diessel, Barbara Dogiami, Kirsten Dorn-Weitzel, Monika Ernst, Grit Faulmann, Baerbel Fetscher, Thomas Forst, Gabriele Freyer-Lahres, Klaus Funke, Xenia Ganz, Christiane Gleixner, Christoph Hanefeld, Sven Heinrichs, Stephanie Helleberg, Elena Henkel, Gerd Ruediger Hetzel, Caren Hoffmann, Frohmut Jacob, Stephan Jacob, Franziska John, Antonius Jonczyk, Wolfram Kamke, Christiane Klein, Martina Kleinhardt, Werner Kleophas, Christine Kosch, Kristin Kreutzmann, Achim Kühn, Young Hee Lee-Barkey, Alexander Lier, Sarah Maatouk, Joachim Minnich, Michael Mitry, Ilona Muessig, Diana Nicula, Martina Niemann, Joerg Nothroff, Petra Ott, Andreas Pfuetzner, Andreas Pfützner, Frank Pistrosch, Wildgard Pohl, Zdenka Prochazkova, Marlena Retkowska, Heiko Rosin, Daniela Sachsenheimer, Holger Samer, Mazin Sanuri, Axel Schaefer, Frank Schaper, Erik-Delf Schulze, Marita Schulze, Martina Schumann, Thomas Segiet, Veronika Sowa, Hans-Detlev Stahl, Franziska Steinfeldt, Madlen Teige, Bjoern Trieb, Diethelm Tschoepe, Peter Uebel, Bernd Warken, Ingo Weigmann, Klaus Weyland, Klara Wilhelm, Timea Balo, Miklos Balsay, Ilona Bende, Katalin Bezzegh, Zita Birkus, Barbara Buday, Melinda Csomai, Laszlo Deak, Eniko Dezso, Peter Faludi, M Faluvegi, Ilona Fazekas, Agota Feher, Csaba Fejer, Ervin Finta, Agnes Fulcz, Zsolt Gaal, Mihaly Gurzo, Krisztina Hati, Gabriella Herczeg, Ildiko Jozsef, Marta Juhasz, Katalin Keltai, Laszlo Koranyi, Eniko Kulcsar, Krisztina Kun, Andrea Laczko, Botond Literáti-Nagy, Izabella Mezo, Margit Mileder, I Moricz, Károly Nagy, Bela Nagybaczoni, Csaba Nemeth, Agnes Oze, Jozsef Pauer, Eva Peterfai, Bela Polocsanyi, Ferenc Poor, István Reiber, Csaba Salamon, Julia Sebestyen, Ildiko Torok, Marianna Tuu, Andrea Varga, Viktor Vass, Chul Min Ahn, Chulwoo Ahn, Park ByungWon, Hyuk-Jae Chang, Kiyuk Chang, Eui-Young Choi, Han Seok Choi, Jin-Wook Chung, Bum- Kee Hong, Young Joon Hong, Min Su Hyon, Myung Ho Jeong, Shinae Kang, Byeong-Keuk Kim, Ji-Hyun Kim, Ju Han Kim, Kee-Sik Kim, Moo Hyun Kim, Pum-Joon Kim, Soon-Kil Kim, Yong-Seok Kim, Young Kwon Kim, Yoon Seok Koh, Hyuck Moon Kwon, Byoung Kwon Lee, Byung-Wan Lee, Jin Bae Lee, Myoung-Mook Lee, Young-Mee Lim, Pil Ki Min, Jong Sung Park, Jongsuk Park, Keun Ho Park, Sungha Park, Wook Bum Pyun, Se Joong Rim, Dong-Ryeol Ryu, Hong-Seog Seo, Ki Bae Seung, Dong-Ho Shin, Doo Sun Sim, Young Won Yoon, Ilze Andersone, Kristine Babicka, Inga Balcere, Roberts Barons, Inguna Capkovska, Kristine Geldnere, Inese Grigane, Baiba Jegere, Ilze Lagzdina, Lija Mora, Sigita Pastare, Rota Ritenberga, Janina Romanova, Inta Saknite, Natalja Sidlovska, Jelena Sokolova, Sandra Steina, Iveta Strizko, Dace Teterovska, Brigita Vizina, Lina Barsiene, Gintare Belozariene, Laura Daugintyte-Petrusiene, Nijole Drungiliene, Nijole Garsviene, Ala Grigiene, Vytautas Grizas, Virginija Jociene, Dalia Kalvaitiene, Jugeta Kaupiene, Jurate Kavaliauskiene, Dalia Kozloviene, Ilona Lapteva, Birute Maneikiene, Jolanta Marcinkeviciene, Vaidilija Markauskiene, Salomeja Meiluniene, Almantas Norkus, Rita Norviliene, Vladimiras Petrenko, Ruta Radzeviciene, Gintare Sakalyte, Gediminas Urbonas, Skaiste Urbutiene, Donatas Vasiliauskas, Dzilda Velickiene, Carlos Aguilar, Marco Alcocer, Juan Antonio Avalos-Ramirez, Ramiro Banda-Elizondo, Rubria Bricio-Ramirez, Karla Cardenas Mejia, Francisco Cavazos, Jesus Chapa, Erika Cienfuegos, Astrid De la Peña, Gilberto de la Peña Topete, Manuel Odin De los Rios Ibarra, Daniel Elias, Claudia Flores-Moreno, Pedro Garcia Hernandez, Luis Gerardo Gonzalez, Rosa Linda Guerra Moya, Arturo Guerra-Lopez, Raymundo Hernandez Baylon, Carolina Herrera Colorado, Marisol Herrera-Marmolejo, Neri Islas-Palacios, Esteban Lopez, Fernando Lopez, Agustin Lopez Alvarado, Rosa Isela Luna Ceballos, Enrique Morales Villegas, Gualberto Moreno-Virgen, Rosa Linda Parra Perez, Sara Pascoe Gonzalez, Irving Peralta-Cantu, Roopa Previn, Rosa Ramirez, Rubria Ramirez, Maria Guadalupe Ramos Zavala, Monica Rodriguez, Rocio Salgado-Sedano, Ana Claudia Sanchez-Aguilar, Edith Santa Rosa Franco, Leobardo Sauque-Reyna, Rodrigo Suarez Otero, Ivonne Torres, Enrique Velarde-Harnandez, Juan Villagordoa, Efrain Villeda-Espinoza, Jorge Vital-Lopez, Cristian Jair Zavala- Bello, John Baker, Elaine Barrington-Ward, Thomas Brownless, Richard Carroll, Simon Carson, Michelle Choe, Andrew Corin, Brian Corley, Richard Cutfield, Neelam Dalaman, Paul Dixon, Paul Drury, Keith Dyson, Chris Florkowski, Monica Ford, William Frengley, Colin Helm, Colin Katzen, Jane Kerr, Manish Khanolkar, David Kim, Renata Koops, Jeremy Krebs, Robert Leikis, Kwan Low, Alison Luckey, Richard Luke, Susan Macaulay, Rodney Marks, Catherine McNamara, Dean Millar-Coote, Steven Miller, Naomi Mottershead, James Reid, Narcisa Robertson, Ian Rosen, David Rowe, Ole Schmiedel, Russell Scott, Jeffrey Sebastian, Davitt Sheahan, Victoria Stiebel, Ian Ternouth, Chris Tofield, Dirk Venter, Michael Williams, Miles Williams, Fiona Wu, Simon Young, Malgorzata Arciszewska, Anna Bochenek, Piotr Borkowski, Przemyslaw Borowy, Tomasz Chrzanowski, Edward Czerwinski, Marek Dwojak, Agnieszka Grodzicka, Izabela Janiec, Joanna Jaruga, Ewa Krystyna Jazwinska-Tarnawska, Krystyna Jedynasty, Danuta Juzwiak-Czapiewska, Jadwiga Karczewicz-Janowska, Jan Konieczny, Marek Konieczny, Marek Korol, Maciej Kozina, Ewa Krzyzagorska, Ewa Kucharczyk-Petryka, Roman Laz, Anna Majchrzak, Zdzislawa Mrozowska, Michal Mularczyk, Elzbieta Nowacka, Jadwiga Peczynska, Robert Petryka, Radoslaw Pietrzak, Dorota Pisarczyk-Wiza, Aleksandra Rozanska, Zofia Ruzga, Emilia Rzeszotarska, Malgorzata Sacha, Marzenna Sekulska, Anna Sidorowicz-Bialynicka, Teresa Stasinska, Agnieszka Strzelecka-Sosik, Teresa Swierszcz, Katarzyna Miroslawa Szymkowiak, Olga Turowska, Krystyna Wisniewska, Maciej Wiza, Iwona Wozniak, Katarzyna Zelazowska, Bernadetta Ziolkowska-Gawron, Danuta Zytkiewicz-Jaruga, Adrian Albota, Carmina Alexandru, Rodica Avram, Cornelia Bala, Diana Barbonta, Roxana Barbu, Daniela Braicu, Nicoleta Calutiu, Doina Catrinoiu, Anca Cerghizan, Alina Ciorba, Anca Craciun, Rodica Doros, Livia Duma, Ancuta Dumitrache, Ioana Ferariu, Anca Ferician Moza, Alexandrina Ghergan, Gheorghe Ghise, Mariana Graur, Mihaela Gribovschi, Bogdan Mihai, Laura Mihalache, Madalina Mihalcea, Nicoleta Mindrescu, Magdalena Morosanu, Andrea Morosoanu, Maria Mota, Anca Moza, Valerica Nafornita, Narcisa Natea, Simona Nicodim, Cristina Nita, Adriana Onaca, Mircea Onaca, Cristina Pop, Lavinia Pop, Amorin Popa, Alexandrina Popescu, Luchiana Pruna, Gabriela Roman, Mihaela Rosu, Alexandra Sima, Doina Sipciu, Carmen Narcisa Sitterli-Natea, Iosif Szilagyi, Minodora Tapurica, Adrian Tase, Adriana-Carmen Tutescu, Luminita Vanghelie, Ioana Verde, Adrian Vlad, Mihaela Zarnescu, Roman Akhmetov, Irina Allenova, Irina Avdeeva, Oksana Baturina, Irina Biserova, Nikolay Bokovin, Irina Bondar, Natalia Burova, Galina Chufeneva, Elena Chumachek, Marina Demidova, Alexander Demin, Vera Drobysheva, Irina Egorova, Lev Esenyan, Ekaterina Gelig, Sergey Gilyarevsky, Maria Golshmid, Arseniy Goncharov, Anastasia Gorbunova, Ivan Gordeev, Vera Gorelysheva, Tatiana Goryunova, Irina Grebenshchikova, Roman Ilchenko, Maria Ivannikova, Saule Karabalieva, Juliya Karpeeva, Elena Khaykina, Zhanna Kobalava, Irina Kononenko, Oxana Korolik, Anna Korshunova, Victor Kostenko, Irina Krasnopevtseva, Ludmila Krylova, Polina Kulkova, Irina Kuzmina, Alla Ledyaeva, Sergey Levashov, Natalia Lokhovinina, Vadim Lvov, Narine Martirosyan, Sergey Nedogoda, Rostislav Nilk, Yulia Osmolovskaya, Alexey Panov, Olga Paramonova, Ekaterina Pavlova, Elena Pekareva, Nina Petunina, Svetlana Ponamareva, Galina Reshedko, Alla Salasyuk, Malvina Sepkhanyan, Alexandr Serebrov, Olesya Shabelnikova, Andrey Skvortsov, Olga Smirnova, Oxana Spiridonova, Svetlana Strogova, Evgeny Taratukhin, Sergey Tereschenko, Lubov Trukhina, Olga Tsarkova, Vera Tsoma, Farid Tumarov, Natalya Tyan, Tatiana Tyurina, Svetlana Villevalde, Elena Yankovaya, Ludmila Zarutskaya, Elena Zenkova, Aysha Badat, Frederik Bester, Suzanne Blignaut, Dirk Blom, Susan Booysen, Warren Boyd, Brigitte Brice, Susan Brown, Lesley Burgess, Reina Cawood, Kathleen Coetzee, Hillet Conradie, Tanja Cronje, Douwe de Jong, Graham Ellis, Shaunagh Emanuel, Ingrid Engelbrecht, Sharne Foulkes, Done Fourie, Gilbert Gibson, Thirumani Govender, Sumayah Hansa, Allana Colleen Hemus, Firzana Hendricks, Marshall Heradien, Chantelle Holmgren, Zaheer Hoosain, Emile Horak, Johannes Howard, Ignatius Immink, E. Janari, Daksha Jivan, Karl Klusmann, Weik Labuschagne, Yen-yu Lai, Gulam Latiff, J. Lombaard, Hanlie Lottering, Ronel Meeding, Shirley Middlemost, Haroon Mitha, Ismail Mitha, Sandile Mkhwanazi, Rajendran Moodley, Almeri Murray, Dany Musungaie, Yasmin Osman, Kirsten Peacey, Larisha Pillay-Ramaya, Catharina Pretorius, Hans Prozesky, Mahomed Sarvan, E Scholtz, Attila Sebesteny, Bianca Skinner, Michael Skriker, M Smit, Anna-Marie Stapelberg, Nicolaas Swanepoel, Dorothea Urbach, Dina van Aswegen, Francois van Zyl, Louis Van Zyl, Esme Venter, Shahid Wadvalla, Jeffrey Wing, Karen Wolmarans, Cristina Abreu, Pilar Aguilà, Eva Aguilera, Nuria Alonso, Carmen Alvarez, Priscila Cajas, Jose Carlos Castro, Roger Codinachs, Jose Contreras, Maria Jose Coves, Carmen Fajardo, Juan Carlos Ferrer, Neus Font, Mar Garcia, Maria Apolonia Gil, Fernando Gomez, Lluis Alberto Gomez, Jose Gonzalbez, Jose Luis Griera, Luís Masmiquel, Didac Mauricio, Silvia Narejos Perez, Juana Ana Nicolau, Olga Noheda Contreras, Josefina Olivan, Josefina Olivares, Emilio Ortega, Silvia Pellitero, Salvador Pertusa, Ferran Rius, Irene Rodriguez, Carlos Sánchez-Juan, Dolores Santos, Berta Soldevila, David Subias, Manel Terns, Carlos Trescoli, Judith Vilaplana, Alicia Villanueva, Jaan Albo, Kjell Antus, Mattias Axelsson, Lisa Bergström, Emil Binsell-Gerdin, Kurt Boman, Fabian Botond, Annika Dotevall, Anna Graipe, C Jarnet, Jessica Kaminska, Anders Kempe, Michael Korhonen, Carina Linderfalk, Bo Liu, Karl Ljungstroem, Karl Ljungström, Lennart Malmqvist, Linda Mellbin, Thomas Mooe, Peter Nicol, Anders Norrby, Ake Ohlsson, Annika Rosengren, Jan Saaf, Staffan Salmonsson, Olof Strandberg, Karl-Axel Svensson, Bengt-Olov Tengmark, Georgios Tsatsaris, Anders Ulvenstam, Peter Vasko, Chwen-Tzuei Chang, Hsin-Mei Chang, Jung-Fu Chen, To-Pang Chen, Ming-Min Chung, Chia-Po Fu, Te-Lin Hsia, Shih-Che Hua, Ming-Chun Kuo, Chia-ln Lee, I-Te Lee, Kae-Woei Liang, Shih Yi Lin, Chieh-Hsiang Lu, Wen-Ya Ma, Dee Pei, Feng-Chih Shen, Ching-Chieh Su, Shuo-Wei Su, Tsai-Sung Tai, Wan-Ni Tsai, Yi-Ting Tsai, Shih-Chen Tung, Jun-Sing Wang, Hui-I Yu, Ahmed Al-Qaissi, Vijayaraman Arutchelvam, Stephen Atkin, Simon Au, Myint Myint Aye, Stephen Bain, Cristina Bejnariu, Patrick Bell, Deepak Bhatnagar, Rudy Bilous, Neil Black, Ursula Brennan, Barbara Brett, Jana Bujanova, Elaine Chow, Andrew Collier, Amanda Combe, Christopher Courtney, Hamish Courtney, James Crothers, Patrick Eavis, Jackie Elliott, Salvatore Febbraro, Jim Finlayson, Rajiv Gandhi, Sharon Gillings, Jonathan Hamling, Roy Harper, Tim Harris, Kahal Hassan, Simon Heller, Alison Jane, Zeeshan Javed, Tim Johnson, Stephen Jones, Adele Kennedy, David Kerr, Brian Kilgallon, Judith Konya, John Lindsay, Lina Lomova-Williams, Helen Looker, David MacFarlane, Sandra Macrury, Iqbal Malik, Rory McCrimmon, Douglas McKeith, John McKnight, Biswa Mishra, Racha Mukhtar, Ciara Mulligan, Maurice O'Kane, Tolu Olateju, Ian Orpen, Tristan Richardson, Desmond Rooney, Shorsha Bae Ross, Thozhukat Sathyapalan, Naveen Siddaramaiah, Lee Euan Sit, Jeffrey Stephens, Frances Turtle, Ammar Wakil, Emma Walkinshaw, Asem Ali, Robert Anderson, Richard Arakaki, Omar Aref, Mehrdad Kevin Ariani, David Arkin, Salomon Banarer, George Barchini, Arti Bhan, Kelley Branch, Donald Brautigam, Stephen Brietzke, Maridez Brinas, Yudit Brito, Casey Carter, Kimberely Casagni, Sabina Casula, Simon Chakko, Seth Charatz, Dale Childress, Lisa Chow, Malgorzata Chustecka, Subha Clarke, Lisa Cohen, Barry Collins, Gildred Colon Vega, Angel Comulada-Rivera, Gregorio Cortes-Maisonet, Matthew Davis, Jose de Souza, Cyrus Desouza, Mary Dinnan, Bobbi Duffy-Hidalgo, Barbara Dunn, Julia Dunn, Marshall Elman, James Felicetta, Stuart Finkelstein, David Fitz-Patrick, Hermes Florez, Alan Forker, Wayne Fowler, Sonja Fredrickson, Zachary Freedman, Brooke Gainey Narron, Kristin Gainey-Ferree, Michael Gardner, Christian Gastelum, Stephen Giddings, Eve Gillespie, Michael Paul Gimness, Gary Goldstein, Maria Gomes, Nelson Gomez, Timothy Gorman, Ketan Goswami, Arthur Graves, Scott Hacking, Charles Hall, Lenita Hanson, Sherman Harman, David Heber, Robert Henry, Janette Hiner, Irl Hirsch, Priscilla Hollander, Thomas Hooker, Barry Horowitz, Laura Hoste, Loli Huang, Minh Huynh, Dan Hyman, Soha Idriss, Ali Iranmanesh, Dennis Karounos, Moti Kashyap, Lois Katz, William Kaye, Yevgeniy Khaiton, Romesh Khardori, Timothy Kitchen, Andrew Klein, Wendi Knffem, Mikhail Kosiborod, Nicola Kreglinger, Davida Kruger, Anubhav Kumar, Ivan Laboy, Patricia Larrabee, Laura Larrick, Donna Lawson, Mike Ledet, James Lenhard, James Levy, George Li, Zhaoping Li, David Lieb, April Limcolioc, Jane Lions-Patterson, Daniel Lorber, Daniel Lorch, Michael Lorrello, Peter Lu, Kathryn Jean Lucas, Siu-Ling Ma, Michael MacAdams, Michelle Magee, Alexander Magno, Aparna Reddy Mahakala, Jennifer Marks, Anthony McCall, William McClanahan, Carole McClary, Lydia Melendez, John Melish, Deanna Michaud, Christopher Miller, Neil Miller, Pablo Mora, Marriyam Moten, Sunder Mudaliar, Gregory Myrick, Puneet Narayan, Mike Nassif, Karena Neri, Tabitha Newton, Patricia Niblack, Philip Nicol, Ebenezer Nyenwe, A. Ola Odugbesan, Yolanda Okorocha, Ramón Ortiz Carrasquillo, Kwame Osei, Coromoto Palermo, Hiren Patel, Krishna Patel, Cindy Pau, Michael Perley, Sanford Plevin, Elena Plummer, Richard Powell, Mohammed Qintar, Rex Rawls, John Reyes-Castano, Lillian Reynolds, Robert Richards, Julio Rosenstock, Caroline Rowe, Jahandar Saleh, Sony Sam, Alfredo Sanchez, Donald Sander, Bruce Sanderson, Virginia Savin, Elizabeth Seaquist, Jayendra Shah, Serena Shi, Vijay Shivaswamy, Tammi Shlotzhauer, David Shore, Bobbie Skukowski, Kyaw Soe, Vesna Solheim, Joseph Soufer, Helmut Steinberg, Jaime Steinsapir, Phillip Tarkington, Debra Thayer, Stephen Thomson, James Thrasher, Joseph Tibaldi, Jeff Tjaden, Oberto Tores, Dace Trence, Subbulaxmi Trikudanathan, Jagdeesh Ullal, Gabriel Uwaifo, Anthony Vo, Kenny Vu, Damandeep Walia, Karen Weiland, Fred Whitehouse, Thomas Wiegmann, Kathleen Wyne, Alan Wynne, Kevin Yuen, Joel Zaretzky, James Zebrack, Franklin Zieve, William Zigrang, and Everest

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Recombinant Fusion Proteins, Placebo-controlled study, Glucagon-Like Peptides, 030204 cardiovascular system & hematology, Placebo, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, law, Internal medicine, Medicine, Albuminuria, Humans, Hypoglycemic Agents, Diabetic Nephropathies, 030212 general & internal medicine, Renal replacement therapy, Aged, Intention-to-treat analysis, business.industry, Hazard ratio, General Medicine, Middle Aged, medicine.disease, Immunoglobulin Fc Fragments, Diabetes Mellitus, Type 2, Creatinine, Dulaglutide, Female, business, medicine.drug, Kidney disease, Glomerular Filtration Rate
Abstract

Digital, Background: Two glucagon-like peptide-1 (GLP-1) receptor agonists reduced renal outcomes in people with type 2 diabetes at risk for cardiovascular disease. We assessed the long-term effect of the GLP-1 receptor agonist dulaglutide on renal outcomes in an exploratory analysis of the REWIND trial of the effect of dulaglutide on cardiovascular disease. Methods: REWIND was a multicentre, randomised, double-blind, placebo-controlled trial at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo and followed up at least every 6 months for outcomes. Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs) were estimated from urine and serum values measured in local laboratories every 12 months. The primary outcome (first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes), secondary outcomes (including a composite microvascular outcome), and safety outcomes of this trial have been reported elsewhere. In this exploratory analysis, we investigate the renal component of the composite microvascular outcome, defined as the first occurrence of new macroalbuminuria (UACR >33·9 mg/mmol), a sustained decline in eGFR of 30% or more from baseline, or chronic renal replacement therapy. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01394952. Findings: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). At baseline, 791 (7·9%) had macroalbuminuria and mean eGFR was 76·9 mL/min per 1·73 m2 (SD 22·7). During a median follow-up of 5·4 years (IQR 5·1-5·9) comprising 51 820 person-years, the renal outcome developed in 848 (17·1%) participants at an incidence rate of 3·5 per 100 person-years in the dulaglutide group and in 970 (19·6%) participants at an incidence rate of 4·1 per 100 person-years in the placebo group (hazard ratio [HR] 0·85, 95% CI 0·77-0·93; p=0·0004). The clearest effect was for new macroalbuminuria (HR 0·77, 95% CI 0·68-0·87; p, Ciencias Médicas y de la Salud

Published
2019

103. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial

Author

Hertzel C Gerstein, Helen M Colhoun, Gilles R Dagenais, Rafael Diaz, Mark Lakshmanan, Prem Pais, Jeffrey Probstfield, Jeffrey S Riesmeyer, Matthew C Riddle, Lars Rydén, Denis Xavier, Charles Messan Atisso, Leanne Dyal, Stephanie Hall, Purnima Rao-Melacini, Gloria Wong, Alvaro Avezum, Jan Basile, Namsik Chung, Ignacio Conget, William C Cushman, Edward Franek, Nicolae Hancu, Markolf Hanefeld, Shaun Holt, Petr Jansky, Matyas Keltai, Fernando Lanas, Lawrence A Leiter, Patricio Lopez-Jaramillo, Ernesto German Cardona Munoz, Valdis Pirags, Nana Pogosova, Peter J Raubenheimer, Jonathan E Shaw, Wayne H-H Sheu, Theodora Temelkova-Kurktschiev, Mercedes Abella, Andrea Alebuena, Sandra Almagro, Eduardo Amoroso, Paula Anadon, Elizabeth Andreu, Guillermo Aristimuño, Maria Arzadun, Maria Barbieri, Raul Barcudi, Ines Bartolacci, Gabriel Bolobanich, Anselmo Bordonava, Miguel Bustamante Labarta, Betina Bustos, Alberto Caccavo, Alejandra Camino, Maria Cantero, Maria Carignano, Luis Cartasegna, Marcela Cipullo, Víctor Commendatore, Victoria Conosciuto, Osvaldo Costamagna, Claudia Crespo, Jose Cuello, Carlos Cuneo, Sandra Cusimano, Sofia Dean, Claudio Dituro, Andrea Dominguez, Miguel Farah, Alberto Fernandez, Florencia Fernandez, Adriana Ferrari, Patricia Flammia, Jose Fuentealba, Karina Beatriz Gallardo, Celso Garcia, Ruben Garcia Duran, Marcelo Garrido, Rodolfo Gavicola, Claudio Gerbaudo, Graciela Gilli, Ana Paula Giotto, Pedro Godoy Bolzán, Oscar Gomez Vilamajo, Fernando Guerlloy, Cristian Guridi, Narcisa Gutierrez Garrido, Eduardo Hasbani, Sonia Hermida, Miguel Hominal, Adrian Hrabar, Adrián Ingaramo, Alejandra Izzicupo, Mario Krynski, Mariana Lagrutta, Paulina Lanchiotti, Maria Langhe, Veronica Leonard, Javier Llanos, Ricardo Lopez Santi, Jorge Lowenstein, Cecilia Luquez, Ignacio Mackinnon, Melina Mana, Sara Manzur, Javier Marino, Carolina Martella, Roger Martinez, Re Matias, Javier Matkovich, Monica Meritano, Oscar Montaña, María Mulazzi, Juan Ochoa, Gustavo Paterlini, María Pelagagge, Maria Elena Peralta Lopez, Aldo Prado, Lorena Pruyas, Martín Racca, Carola Ricotti, Carolina Rodriguez, Mariano Romero Vidomlansky, Ricardo Ronderos, Ana Laura Sadowski, Jorgelina Sala, Alejandro Sánchez, Andrea Santoro, Lilia Schiavi, Mariano Sein, Virginia Sernia, Leonardo Serra, Maximiliano Sicer, Tomas Smith, Leonardo Soso, Georgina Sposetti, Andrea Steinacher, Jorge Stival, Jorge Tedesco, Hugo Tonin, Mauro Tortolo, Maria Ulla, Julio Vallejos, Marisa Vico, Luciana Virgillito, Virginia Visco, Daniel Vogel, Florencia Waisman, César Zaidman, Noemi Zucchiatti, Imran Badshah, Neale Cohen, Peter Colman, David Colquhoun, Timothy Davis, Spiros Fourlanos, Greg Fulcher, Jane Hamlyn, Cilla Haywood, Samantha Hocking, Maeve Huchinson, William Jeffries, Mervyn Kyl, Clement Lo, PeakMann Mah, Ashley Makepeace, Dolly Marope, Natalie Nanayakkar, Alison Nankervis, Neil Palmer, Barbara Palolus, Satish Pillai, Sarah Price, Joseph Proietto, Anne Reutens, Natassia Rodrigo, Abdul Sheikh, Greg Smith, Michelle So, Georgia Soldatos, Bronwyn Stuckey, Priya Sumithran, Helena Teede, Parind Vora, Lyn Williams, Eduardo Abib, Christiani Adão Poço, Érica Ferreira Alves, Janaina Andreatta Bernardi Barea, Livia Avezum Oliveira, Denise Ludovico da Costa de Castro, Ivan Correa da Cruz, Midiã Costa, Ivan Cruz, Sidney Cunha, Marco Antonio Vieira Da Silva, Renata de Carvalho Camara Bona, Bruna de Paula, Freddy Eliaschewitz, Guilherme Fazolli, Carlos Alberto Ferreira Filho, Jose Fortes, Cesar França, Denise Reis Franco, Paulo Roberto Genestreti, Flavio Giorgeto, Rodrigo Marques Gonçalves, Michele Elka Grossman, Ana Claudia Henrique Marcelino, Mauro Hernandes, Ana Horta, Cristiano Jaeger, Midia Kaneblai, Cecilia Kauffman Rutenberg, Jose Francisco Kerr Saraiva, Maria Angelica Lemos, Lilia Maia, Euler Roberto Manenti, Mariana Marques, Cynthia Melissa Valerio, Rodrigo Moreira, Flávia Mothé, Osana Maria Mouco, Philip Moura, José Carlos Moura Jorge, Carlos Nakashima, Marcelo Nakazone, Thiago Napoli, Cristiane Nunes, Joao Eduardo Nunes Salles, Karla Oliveira, Marcela Oliveira, Gracielly de Souza Pantano, Fabio Petri, Leonardo Piazza, Andreia Carla Pires, Patricia Pizzato, Sergio Prata, Dalton Precoma, Rafael Rech, Gilmar Reis, Heleno Reis, Elisabete Resende, Jose Ribas Fortes, Sylka Rodovalho, Fabio Rossi dos Santos, Joao Eduardo Salles, Célia Regina Sampaio, Thiago Santos, Vanessa Santos dos Santos, Tulio Silva e Quadros, Daniel Silveira, Katia Nunes Siqueira, M Teireira, Marcelo Uehara, C Valerio, Henrique Vianna, Maria Helena Vidotti, Guilherme de Lima Visconti, Maria Teresa Zanella, Viktoriya Andreeva, Radoslav Borisov, Nikolay Botushanov, Georgi Dimitrov, Kameliya Dimova, Tsvetan Dragoychev, Valentina Grigorova, Valentina Gushterova, Ivaylo Ivanov, Tatyana Kocelova, Dimo Kurktschiev, Milena Miletieva, Neli Nenkova-Gugusheva, Ralitsa Pancheva, Maria Pavlova, Dimitar Raev, Vesela Spasova, Anastas Stoikov, Dimitar Troev, Todor Yanev, Mariana Yoncheva-Mihaylova, Alexander Abitbol, Buki Ajala, Abdullh Alguwaihes, Jean-Luc Ardilouze, Nahla Aris-Jilwan, Amel Arnaout, Ronnie Aronson, Nadeem Aslam, Sandra Babin, Jean-Patrice Bailargeon, Allan Bailey, Harpreet Bajaj, Christian Beauchesne, Sorin Beca, Andre Belanger, Alan Bell, Diego Bellabarba, Lori Berard, Brian Berenbaum, Vincent Bergeron, Joseph Berlingieri, Frédéric Bernier, Phoebe Bishara, David Blank, Ian Blumer, Suzanne Brault, Donald Breton, André Carpentier, James Cha, Prakash Chandra, Jean-Louis Chiasson, James R Conway, Ghyslaine Couture, Nathalie Couture, Gilles Dagenais, Dyotirmoy Datta, Giuseppe D'Ignazio, Richard Dumas, Didier Fay, Andre Frechette, Louise Frenette, Daisy Fung, Nathalie Gagnon, Meri Galter, Jean Garon, Jean Sebastien Gauthier, Christian Geadah, Jeremy Gilbert, Ronald Girard, Ronald Goldenberg, Loren David Grossman, Nikhil Gupta, Jean-Pierre Halle, Marie-France Hivert, Ghislaine Houde, Robyn Houlden, Irene Hramiak, Ted Jablonski, Akshay Jain Jain, Hasnain Khandwala, Munish Khosla, C Lachance, Emilie Laflamme, Marie-France Langlois, Luc Larivee, Joanne Liutkus, Heather Lochnan, Saleem Malik, Charlotte McDonald, Pravinsagar Mehta, John Mihailidis, Alain Milot, Priya Narula, Patrice Nault, Arun Nayar, William Nisker, Gilles Ouellet, Jean Palardy, Minta Patel, Terri Paul, Sue Pedersen, Patrice Perron, Marie-Hélène Pesant, Paul Poirier, Marie-Claude Poulin, Zubin Punthakee, Waheed Rehman, Stuart Ross, P Sagar, Nouhad Saliba, Sam Sandler, Alicia Schiffrin, Robert Schlosser, Anila Seth-Sharma, Mark Sherman, David Sionit, Tharsan Sivakumar, Juan Soto, Eric St-Amour, Oren Steen, Jack Sussman, Adam Telner, Sheldon Tobe, David-Yaw Twum-Barima, Audrey Van Zanten, Nicole VanRossum, Jonathan Vecchiarelli, Rick Ward, John Wessengel, Stanley Weisnagel, Igor Wilderman, Vincent Woo, Natalia Yakubovich, Jean-Francois Yale, Zeina Yared, Monica Acevedo, Maria Loreto Aguirre, Andres Aizman, Maria Soledad Barroso, Leonardo Cobos, Alfredo Danin Vargas, Barbara Descalzi, Gonzalo Godoy, Elio Grumberg, Rodolfo Lahsen, Gladys Larenas, Eugenia Ortiz, Javier Paredes, Sergio Potthoff, Eva Retamal, Luis Rojas, Manuel Salgado, Claudio Santibanez, Carmen Solis, Benjamin Stokins, Jose Accini, Javier Acebedo, Lina Maria Agudelo Baena, Soraya Alarcon, Juliana Angel, Edgar Arcos, M Aroca Martinez, Leonor Atuesta, Jose Balaguera, Doris Ballestas, Sandra Isabel Barrera, Rosmy Barrios Reyes, Adolfo Bayona, Andres Bermudez, Diego Zarate Bernal, Marco Blanquicett, Victor Bravo, Wendy Bueno, Alvaro Burbano Delgado, Alberto Cadena, Andres Cadena, Sandra Caicedo, Carlos Celemin, Ricardo Consuegra, Cristhian Contreras Pimienta, Kelly Johenis Corredor, Carlos Cure, Lizeth Dayana De La Hoz Rueda, Erika Delgado, Sarahy Diaz, Marta Diego, Anabell Donado, William Encinales Sanabria, Juliana Escobar, Gillian Escorcia, Leonardo Forero, Laura Fuentes, Maria Garcia, Henry Garcia Lozada, Luis Garcia Ortiz, Angela Giraldo, Laura Gomez Gonzalez, Javier Granada, Corina Gutierrez, Natalia Henao, Edwin Hernandez, Olga Maria Herrera Uejbe, Juan Diego Higuera Cobos, Jaime Ibarra Gómez, Edwin Hernandez Jaimes, Monica Jaramillo, Nicolas Jaramillo, Carlos Jaramillo Gomez, Monica Jaramillo Sanchez, Ivonne Jarava Durán, Catalina Lopez Ceballos, Claudia Madrid, Elias María Amastha, Jennifer Mercado, Dora Ines Molina, Jessica Molina Soto, Carlos Montoya, Alexander Morales, Carolina Muñoz, Luis Alejandro Orozco, Oscar Osorio, Jorge Mario Palmera Sanchez, Adwar Peña, Jose Perez, Juan Perez Agudelo, Germán Pérez Amador, Carlos Pertuz, Irina Posada, Carlos Puerta, Adalberto Quintero, Diana Quiroz, Carmen Rendon, Alberto Reyes, Alvaro Reyes, Diana Ripoll, Carlos Rivera, Maria Rocha, Jose F Rodriguez, Kervis Asid Rodriguez Villanueva, Javier Emilio Rodriguez Zabala, Sindy Rojas, Maria Romero, Ricardo Rosero, Angelica Rocio Rosillo Cardenas, Lina Rueda, Gregorio Sanchez, Tatiana Sanchez, Arístides Sotomayor Herazo, Monica Suarez, Mariana Torres, Freddy Trujillo, Miguel Urina, Lazaro Van Strahlen, Carlos Velandia, Carolina Velasquez Guzman, Elizabeth Velazquez, Tatiana Vidal Prada, Juan Pablo Yepez Alvaran, Diego Zarate, Jana Andelova, Radka Benesova, Barbara Buzova, Vladimir Cech, Ida Chodova, Miroslav Choura, Antonin Dufka, Andrea Gamova, Jakub Gorgol, Tomas Hala, Hana Havlova, Dagmar Hlavkova, Petra Horanska, Juliana Ilcisin-Valova, Petra Jenickova, Ondrej Jerabek, Ilona Kantorova, Katerina Kolomaznikova, Iva Kopeckova, Miroslava Kopeckova, Karel Linhart, Tomas Linhart, Jan Malecha, Emilia Malicherova, Dana Neubauerova, Martina Oznerova, Radan Partys, Eva Pederzoliova, Maria Petrusova, Vera Prymkova, Eva Racicka, Ida Reissova, Eva Roderova, Libor Stanek, Alena Striova, Dana Svarcova, Petr Svoboda, Emilia Szeghy Malicharova, Jan Urge, Ladislav Vesely, Bedich Wasserburger, Hilde Wasserburgerova, Emil Zahumensky, Vaclav Zamrazil, Hasan Alawi, Ernestos Anastasiadis, Elisabeth Axthelm, Tasso Bieler, Christina Buhrig, Elizaveta Degtyareva, Frank Dellanna, Karl-Michael Derwahl, Stephan Diessel, Barbara Dogiami, Kirsten Dorn-Weitzel, Monika Ernst, Grit Faulmann, Baerbel Fetscher, Thomas Forst, Gabriele Freyer-Lahres, Klaus Funke, Xenia Ganz, Christiane Gleixner, Christoph Hanefeld, Sven Heinrichs, Stephanie Helleberg, Elena Henkel, Gerd Ruediger Hetzel, Caren Hoffmann, Frohmut Jacob, Stephan Jacob, Franziska John, Antonius Jonczyk, Wolfram Kamke, Christiane Klein, Martina Kleinhardt, Werner Kleophas, Christine Kosch, Kristin Kreutzmann, Achim Kühn, Young Hee Lee-Barkey, Alexander Lier, Sarah Maatouk, Joachim Minnich, Michael Mitry, Ilona Muessig, Diana Nicula, Martina Niemann, Joerg Nothroff, Petra Ott, Andreas Pfuetzner, Andreas Pfützner, Frank Pistrosch, Wildgard Pohl, Zdenka Prochazkova, Marlena Retkowska, Heiko Rosin, Daniela Sachsenheimer, Holger Samer, Mazin Sanuri, Axel Schaefer, Frank Schaper, Erik-Delf Schulze, Marita Schulze, Martina Schumann, Thomas Segiet, Veronika Sowa, Hans-Detlev Stahl, Franziska Steinfeldt, Madlen Teige, Bjoern Trieb, Diethelm Tschoepe, Peter Uebel, Bernd Warken, Ingo Weigmann, Klaus Weyland, Klara Wilhelm, Timea Balo, Miklos Balsay, Ilona Bende, Katalin Bezzegh, Zita Birkus, Barbara Buday, Melinda Csomai, Laszlo Deak, Eniko Dezso, Peter Faludi, M Faluvegi, Ilona Fazekas, Agota Feher, Csaba Fejer, Ervin Finta, Agnes Fulcz, Zsolt Gaal, Mihaly Gurzo, Krisztina Hati, Gabriella Herczeg, Ildiko Jozsef, Marta Juhasz, Katalin Keltai, Laszlo Koranyi, Eniko Kulcsar, Krisztina Kun, Andrea Laczko, Botond Literáti-Nagy, Izabella Mezo, Margit Mileder, I Moricz, Károly Nagy, Bela Nagybaczoni, Csaba Nemeth, Agnes Oze, Jozsef Pauer, Eva Peterfai, Bela Polocsanyi, Ferenc Poor, István Reiber, Csaba Salamon, Julia Sebestyen, Ildiko Torok, Marianna Tuu, Andrea Varga, Viktor Vass, Chul Min Ahn, Chulwoo Ahn, Park ByungWon, Hyuk-Jae Chang, Kiyuk Chang, Eui-Young Choi, Han Seok Choi, Jin-Wook Chung, Bum- Kee Hong, Young Joon Hong, Min Su Hyon, Myung Ho Jeong, Shinae Kang, Byeong-Keuk Kim, Ji-Hyun Kim, Ju Han Kim, Kee-Sik Kim, Moo Hyun Kim, Pum-Joon Kim, Soon-Kil Kim, Yong-Seok Kim, Young Kwon Kim, Yoon Seok Koh, Hyuck Moon Kwon, Byoung Kwon Lee, Byung-Wan Lee, Jin Bae Lee, Myoung-Mook Lee, Young-Mee Lim, Pil Ki Min, Jong Sung Park, Jongsuk Park, Keun Ho Park, Sungha Park, Wook Bum Pyun, Se Joong Rim, Dong-Ryeol Ryu, Hong-Seog Seo, Ki Bae Seung, Dong-Ho Shin, Doo Sun Sim, Young Won Yoon, Ilze Andersone, Kristine Babicka, Inga Balcere, Roberts Barons, Inguna Capkovska, Kristine Geldnere, Inese Grigane, Baiba Jegere, Ilze Lagzdina, Lija Mora, Sigita Pastare, Rota Ritenberga, Janina Romanova, Inta Saknite, Natalja Sidlovska, Jelena Sokolova, Sandra Steina, Iveta Strizko, Dace Teterovska, Brigita Vizina, Lina Barsiene, Gintare Belozariene, Laura Daugintyte-Petrusiene, Nijole Drungiliene, Nijole Garsviene, Ala Grigiene, Vytautas Grizas, Virginija Jociene, Dalia Kalvaitiene, Jugeta Kaupiene, Jurate Kavaliauskiene, Dalia Kozloviene, Ilona Lapteva, Birute Maneikiene, Jolanta Marcinkeviciene, Vaidilija Markauskiene, Salomeja Meiluniene, Almantas Norkus, Rita Norviliene, Vladimiras Petrenko, Ruta Radzeviciene, Gintare Sakalyte, Gediminas Urbonas, Skaiste Urbutiene, Donatas Vasiliauskas, Dzilda Velickiene, Carlos Aguilar, Marco Alcocer, Juan Antonio Avalos-Ramirez, Ramiro Banda-Elizondo, Rubria Bricio-Ramirez, Karla Cardenas Mejia, Francisco Cavazos, Jesus Chapa, Erika Cienfuegos, Astrid De la Peña, Gilberto de la Peña Topete, Manuel Odin De los Rios Ibarra, Daniel Elias, Claudia Flores-Moreno, Pedro Garcia Hernandez, Luis Gerardo Gonzalez, Rosa Linda Guerra Moya, Arturo Guerra-Lopez, Raymundo Hernandez Baylon, Carolina Herrera Colorado, Marisol Herrera-Marmolejo, Neri Islas-Palacios, Esteban Lopez, Fernando Lopez, Agustin Lopez Alvarado, Rosa Isela Luna Ceballos, Enrique Morales Villegas, Gualberto Moreno-Virgen, Rosa Linda Parra Perez, Sara Pascoe Gonzalez, Irving Peralta-Cantu, Roopa Previn, Rosa Ramirez, Rubria Ramirez, Maria Guadalupe Ramos Zavala, Monica Rodriguez, Rocio Salgado-Sedano, Ana Claudia Sanchez-Aguilar, Edith Santa Rosa Franco, Leobardo Sauque-Reyna, Rodrigo Suarez Otero, Ivonne Torres, Enrique Velarde-Harnandez, Juan Villagordoa, Efrain Villeda-Espinoza, Jorge Vital-Lopez, Cristian Jair Zavala- Bello, John Baker, Elaine Barrington-Ward, Thomas Brownless, Richard Carroll, Simon Carson, Michelle Choe, Andrew Corin, Brian Corley, Richard Cutfield, Neelam Dalaman, Paul Dixon, Paul Drury, Keith Dyson, Chris Florkowski, Monica Ford, William Frengley, Colin Helm, Colin Katzen, Jane Kerr, Manish Khanolkar, David Kim, Renata Koops, Jeremy Krebs, Robert Leikis, Kwan Low, Alison Luckey, Richard Luke, Susan Macaulay, Rodney Marks, Catherine McNamara, Dean Millar-Coote, Steven Miller, Naomi Mottershead, James Reid, Narcisa Robertson, Ian Rosen, David Rowe, Ole Schmiedel, Russell Scott, Jeffrey Sebastian, Davitt Sheahan, Victoria Stiebel, Ian Ternouth, Chris Tofield, Dirk Venter, Michael Williams, Miles Williams, Fiona Wu, Simon Young, Malgorzata Arciszewska, Anna Bochenek, Piotr Borkowski, Przemyslaw Borowy, Tomasz Chrzanowski, Edward Czerwinski, Marek Dwojak, Agnieszka Grodzicka, Izabela Janiec, Joanna Jaruga, Ewa Krystyna Jazwinska-Tarnawska, Krystyna Jedynasty, Danuta Juzwiak-Czapiewska, Jadwiga Karczewicz-Janowska, Jan Konieczny, Marek Konieczny, Marek Korol, Maciej Kozina, Ewa Krzyzagorska, Ewa Kucharczyk-Petryka, Roman Laz, Anna Majchrzak, Zdzislawa Mrozowska, Michal Mularczyk, Elzbieta Nowacka, Jadwiga Peczynska, Robert Petryka, Radoslaw Pietrzak, Dorota Pisarczyk-Wiza, Aleksandra Rozanska, Zofia Ruzga, Emilia Rzeszotarska, Malgorzata Sacha, Marzenna Sekulska, Anna Sidorowicz-Bialynicka, Teresa Stasinska, Agnieszka Strzelecka-Sosik, Teresa Swierszcz, Katarzyna Miroslawa Szymkowiak, Olga Turowska, Krystyna Wisniewska, Maciej Wiza, Iwona Wozniak, Katarzyna Zelazowska, Bernadetta Ziolkowska-Gawron, Danuta Zytkiewicz-Jaruga, Adrian Albota, Carmina Alexandru, Rodica Avram, Cornelia Bala, Diana Barbonta, Roxana Barbu, Daniela Braicu, Nicoleta Calutiu, Doina Catrinoiu, Anca Cerghizan, Alina Ciorba, Anca Craciun, Rodica Doros, Livia Duma, Ancuta Dumitrache, Ioana Ferariu, Anca Ferician Moza, Alexandrina Ghergan, Gheorghe Ghise, Mariana Graur, Mihaela Gribovschi, Bogdan Mihai, Laura Mihalache, Madalina Mihalcea, Nicoleta Mindrescu, Magdalena Morosanu, Andrea Morosoanu, Maria Mota, Anca Moza, Valerica Nafornita, Narcisa Natea, Simona Nicodim, Cristina Nita, Adriana Onaca, Mircea Onaca, Cristina Pop, Lavinia Pop, Amorin Popa, Alexandrina Popescu, Luchiana Pruna, Gabriela Roman, Mihaela Rosu, Alexandra Sima, Doina Sipciu, Carmen Narcisa Sitterli-Natea, Iosif Szilagyi, Minodora Tapurica, Adrian Tase, Adriana-Carmen Tutescu, Luminita Vanghelie, Ioana Verde, Adrian Vlad, Mihaela Zarnescu, Roman Akhmetov, Irina Allenova, Irina Avdeeva, Oksana Baturina, Irina Biserova, Nikolay Bokovin, Irina Bondar, Natalia Burova, Galina Chufeneva, Elena Chumachek, Marina Demidova, Alexander Demin, Vera Drobysheva, Irina Egorova, Lev Esenyan, Ekaterina Gelig, Sergey Gilyarevsky, Maria Golshmid, Arseniy Goncharov, Anastasia Gorbunova, Ivan Gordeev, Vera Gorelysheva, Tatiana Goryunova, Irina Grebenshchikova, Roman Ilchenko, Maria Ivannikova, Saule Karabalieva, Juliya Karpeeva, Elena Khaykina, Zhanna Kobalava, Irina Kononenko, Oxana Korolik, Anna Korshunova, Victor Kostenko, Irina Krasnopevtseva, Ludmila Krylova, Polina Kulkova, Irina Kuzmina, Alla Ledyaeva, Sergey Levashov, Natalia Lokhovinina, Vadim Lvov, Narine Martirosyan, Sergey Nedogoda, Rostislav Nilk, Yulia Osmolovskaya, Alexey Panov, Olga Paramonova, Ekaterina Pavlova, Elena Pekareva, Nina Petunina, Svetlana Ponamareva, Galina Reshedko, Alla Salasyuk, Malvina Sepkhanyan, Alexandr Serebrov, Olesya Shabelnikova, Andrey Skvortsov, Olga Smirnova, Oxana Spiridonova, Svetlana Strogova, Evgeny Taratukhin, Sergey Tereschenko, Lubov Trukhina, Olga Tsarkova, Vera Tsoma, Farid Tumarov, Natalya Tyan, Tatiana Tyurina, Svetlana Villevalde, Elena Yankovaya, Ludmila Zarutskaya, Elena Zenkova, Aysha Badat, Frederik Bester, Suzanne Blignaut, Dirk Blom, Susan Booysen, Warren Boyd, Brigitte Brice, Susan Brown, Lesley Burgess, Reina Cawood, Kathleen Coetzee, Hillet Conradie, Tanja Cronje, Douwe de Jong, Graham Ellis, Shaunagh Emanuel, Ingrid Engelbrecht, Sharne Foulkes, Done Fourie, Gilbert Gibson, Thirumani Govender, Sumayah Hansa, Allana Colleen Hemus, Firzana Hendricks, Marshall Heradien, Chantelle Holmgren, Zaheer Hoosain, Emile Horak, Johannes Howard, Ignatius Immink, E. Janari, Daksha Jivan, Karl Klusmann, Weik Labuschagne, Yen-yu Lai, Gulam Latiff, J. Lombaard, Hanlie Lottering, Ronel Meeding, Shirley Middlemost, Haroon Mitha, Ismail Mitha, Sandile Mkhwanazi, Rajendran Moodley, Almeri Murray, Dany Musungaie, Yasmin Osman, Kirsten Peacey, Larisha Pillay-Ramaya, Catharina Pretorius, Hans Prozesky, Mahomed Sarvan, E Scholtz, Attila Sebesteny, Bianca Skinner, Michael Skriker, M Smit, Anna-Marie Stapelberg, Nicolaas Swanepoel, Dorothea Urbach, Dina van Aswegen, Francois van Zyl, Louis Van Zyl, Esme Venter, Shahid Wadvalla, Jeffrey Wing, Karen Wolmarans, Cristina Abreu, Pilar Aguilà, Eva Aguilera, Nuria Alonso, Carmen Alvarez, Priscila Cajas, Jose Carlos Castro, Roger Codinachs, Jose Contreras, Maria Jose Coves, Carmen Fajardo, Juan Carlos Ferrer, Neus Font, Mar Garcia, Maria Apolonia Gil, Fernando Gomez, Lluis Alberto Gomez, Jose Gonzalbez, Jose Luis Griera, Luís Masmiquel, Didac Mauricio, Silvia Narejos Perez, Juana Ana Nicolau, Olga Noheda Contreras, Josefina Olivan, Josefina Olivares, Emilio Ortega, Silvia Pellitero, Salvador Pertusa, Ferran Rius, Irene Rodriguez, Carlos Sánchez-Juan, Dolores Santos, Berta Soldevila, David Subias, Manel Terns, Carlos Trescoli, Judith Vilaplana, Alicia Villanueva, Jaan Albo, Kjell Antus, Mattias Axelsson, Lisa Bergström, Emil Binsell-Gerdin, Kurt Boman, Fabian Botond, Annika Dotevall, Anna Graipe, C Jarnet, Jessica Kaminska, Anders Kempe, Michael Korhonen, Carina Linderfalk, Bo Liu, Karl Ljungstroem, Karl Ljungström, Lennart Malmqvist, Linda Mellbin, Thomas Mooe, Peter Nicol, Anders Norrby, Ake Ohlsson, Annika Rosengren, Jan Saaf, Staffan Salmonsson, Olof Strandberg, Karl-Axel Svensson, Bengt-Olov Tengmark, Georgios Tsatsaris, Anders Ulvenstam, Peter Vasko, Chwen-Tzuei Chang, Hsin-Mei Chang, Jung-Fu Chen, To-Pang Chen, Ming-Min Chung, Chia-Po Fu, Te-Lin Hsia, Shih-Che Hua, Ming-Chun Kuo, Chia-ln Lee, I-Te Lee, Kae-Woei Liang, Shih Yi Lin, Chieh-Hsiang Lu, Wen-Ya Ma, Dee Pei, Feng-Chih Shen, Ching-Chieh Su, Shuo-Wei Su, Tsai-Sung Tai, Wan-Ni Tsai, Yi-Ting Tsai, Shih-Chen Tung, Jun-Sing Wang, Hui-I Yu, Ahmed Al-Qaissi, Vijayaraman Arutchelvam, Stephen Atkin, Simon Au, Myint Myint Aye, Stephen Bain, Cristina Bejnariu, Patrick Bell, Deepak Bhatnagar, Rudy Bilous, Neil Black, Ursula Brennan, Barbara Brett, Jana Bujanova, Elaine Chow, Andrew Collier, Amanda Combe, Christopher Courtney, Hamish Courtney, James Crothers, Patrick Eavis, Jackie Elliott, Salvatore Febbraro, Jim Finlayson, Rajiv Gandhi, Sharon Gillings, Jonathan Hamling, Roy Harper, Tim Harris, Kahal Hassan, Simon Heller, Alison Jane, Zeeshan Javed, Tim Johnson, Stephen Jones, Adele Kennedy, David Kerr, Brian Kilgallon, Judith Konya, John Lindsay, Lina Lomova-Williams, Helen Looker, David MacFarlane, Sandra Macrury, Iqbal Malik, Rory McCrimmon, Douglas McKeith, John McKnight, Biswa Mishra, Racha Mukhtar, Ciara Mulligan, Maurice O'Kane, Tolu Olateju, Ian Orpen, Tristan Richardson, Desmond Rooney, Shorsha Bae Ross, Thozhukat Sathyapalan, Naveen Siddaramaiah, Lee Euan Sit, Jeffrey Stephens, Frances Turtle, Ammar Wakil, Emma Walkinshaw, Asem Ali, Robert Anderson, Richard Arakaki, Omar Aref, Mehrdad Kevin Ariani, David Arkin, Salomon Banarer, George Barchini, Arti Bhan, Kelley Branch, Donald Brautigam, Stephen Brietzke, Maridez Brinas, Yudit Brito, Casey Carter, Kimberely Casagni, Sabina Casula, Simon Chakko, Seth Charatz, Dale Childress, Lisa Chow, Malgorzata Chustecka, Subha Clarke, Lisa Cohen, Barry Collins, Gildred Colon Vega, Angel Comulada-Rivera, Gregorio Cortes-Maisonet, Matthew Davis, Jose de Souza, Cyrus Desouza, Mary Dinnan, Bobbi Duffy-Hidalgo, Barbara Dunn, Julia Dunn, Marshall Elman, James Felicetta, Stuart Finkelstein, David Fitz-Patrick, Hermes Florez, Alan Forker, Wayne Fowler, Sonja Fredrickson, Zachary Freedman, Brooke Gainey Narron, Kristin Gainey-Ferree, Michael Gardner, Christian Gastelum, Stephen Giddings, Eve Gillespie, Michael Paul Gimness, Gary Goldstein, Maria Gomes, Nelson Gomez, Timothy Gorman, Ketan Goswami, Arthur Graves, Scott Hacking, Charles Hall, Lenita Hanson, Sherman Harman, David Heber, Robert Henry, Janette Hiner, Irl Hirsch, Priscilla Hollander, Thomas Hooker, Barry Horowitz, Laura Hoste, Loli Huang, Minh Huynh, Dan Hyman, Soha Idriss, Ali Iranmanesh, Dennis Karounos, Moti Kashyap, Lois Katz, William Kaye, Yevgeniy Khaiton, Romesh Khardori, Timothy Kitchen, Andrew Klein, Wendi Knffem, Mikhail Kosiborod, Nicola Kreglinger, Davida Kruger, Anubhav Kumar, Ivan Laboy, Patricia Larrabee, Laura Larrick, Donna Lawson, Mike Ledet, James Lenhard, James Levy, George Li, Zhaoping Li, David Lieb, April Limcolioc, Jane Lions-Patterson, Daniel Lorber, Daniel Lorch, Michael Lorrello, Peter Lu, Kathryn Jean Lucas, Siu-Ling Ma, Michael MacAdams, Michelle Magee, Alexander Magno, Aparna Reddy Mahakala, Jennifer Marks, Anthony McCall, William McClanahan, Carole McClary, Lydia Melendez, John Melish, Deanna Michaud, Christopher Miller, Neil Miller, Pablo Mora, Marriyam Moten, Sunder Mudaliar, Gregory Myrick, Puneet Narayan, Mike Nassif, Karena Neri, Tabitha Newton, Patricia Niblack, Philip Nicol, Ebenezer Nyenwe, A. Ola Odugbesan, Yolanda Okorocha, Ramón Ortiz Carrasquillo, Kwame Osei, Coromoto Palermo, Hiren Patel, Krishna Patel, Cindy Pau, Michael Perley, Sanford Plevin, Elena Plummer, Richard Powell, Mohammed Qintar, Rex Rawls, John Reyes-Castano, Lillian Reynolds, Robert Richards, Julio Rosenstock, Caroline Rowe, Jahandar Saleh, Sony Sam, Alfredo Sanchez, Donald Sander, Bruce Sanderson, Virginia Savin, Elizabeth Seaquist, Jayendra Shah, Serena Shi, Vijay Shivaswamy, Tammi Shlotzhauer, David Shore, Bobbie Skukowski, Kyaw Soe, Vesna Solheim, Joseph Soufer, Helmut Steinberg, Jaime Steinsapir, Phillip Tarkington, Debra Thayer, Stephen Thomson, James Thrasher, Joseph Tibaldi, Jeff Tjaden, Oberto Tores, Dace Trence, Subbulaxmi Trikudanathan, Jagdeesh Ullal, Gabriel Uwaifo, Anthony Vo, Kenny Vu, Damandeep Walia, Karen Weiland, Fred Whitehouse, Thomas Wiegmann, Kathleen Wyne, Alan Wynne, Kevin Yuen, Joel Zaretzky, James Zebrack, Franklin Zieve, William Zigrang, and Everest

Subjects
Male, medicine.medical_specialty, Recombinant Fusion Proteins, Population, Placebo-controlled study, Glucagon-Like Peptides, Myocardial Infarction, Type 2 diabetes, 030204 cardiovascular system & hematology, Placebo, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, law, Internal medicine, medicine, Humans, Hypoglycemic Agents, 030212 general & internal medicine, education, Aged, education.field_of_study, business.industry, Semaglutide, Hazard ratio, General Medicine, Middle Aged, medicine.disease, Immunoglobulin Fc Fragments, Stroke, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Dulaglutide, Female, business, medicine.drug
Abstract

Digital, Background Three different glucagon-like peptide-1 (GLP-1) receptor agonists reduce cardiovascular outcomes in people with type 2 diabetes at high cardiovascular risk with high glycated haemoglobin A1c (HbA1c) concentrations. We assessed the effect of the GLP-1 receptor agonist dulaglutide on major adverse cardiovascular events when added to the existing antihyperglycaemic regimens of individuals with type 2 diabetes with and without previous cardiovascular disease and a wide range of glycaemic control. Methods This multicentre, randomised, double-blind, placebo-controlled trial was done at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo. Randomisation was done by a computer-generated random code with stratification by site. All investigators and participants were masked to treatment assignment. Participants were followed up at least every 6 months for incident cardiovascular and other serious clinical outcomes. The primary outcome was the first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes), which was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01394952. Findings Between Aug 18, 2011, and Aug 14, 2013, 9901 participants (mean age 66·2 years [SD 6·5], median HbA1c 7·2% [IQR 6·6–8·1], 4589 [46·3%] women) were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). During a median follow-up of 5·4 years (IQR 5·1–5·9), the primary composite outcome occurred in 594 (12·0%) participants at an incidence rate of 2·4 per 100 person-years in the dulaglutide group and in 663 (13·4%) participants at an incidence rate of 2·7 per 100 person-years in the placebo group (hazard ratio [HR] 0·88, 95% CI 0·79–0·99; p=0·026). All-cause mortality did not differ between groups (536 [10·8%] in the dulaglutide group vs 592 [12·0%] in the placebo group; HR 0·90, 95% CI 0·80–1·01; p=0·067). 2347 (47·4%) participants assigned to dulaglutide reported a gastrointestinal adverse event during follow-up compared with 1687 (34·1%) participants assigned to placebo (p, Ciencias Médicas y de la Salud

Published
2019

105. Enhanced Antibacterial Efficacy of Bioceramic Implants Functionalized with Ciprofloxacin: An In Silico and In Vitro Study

Author

Renata-Maria Văruț, Luciana Teodora Rotaru, Diana Cimpoesu, Mihaela Corlade, Cristina Elena Singer, Alin Iulian Silviu Popescu, Cristina Popescu, Iliescu Iulian-Nicolae, Adriana Mocanu, Mihaela Popescu, Mihai Alexandru Butoi, and Oana Elena Nicolaescu

Subjects
bone infections, antibiotics, molecular docking, Pharmacy and materia medica, RS1-441
Abstract

This study explores the antibacterial efficacy and cytotoxicity of ciprofloxacin-functionalized bioceramic implants. We synthesized hydroxyapatite-ciprofloxacin (HACPXCS) composites and applied them to titanium substrates (Ti-HA-CPX), evaluating their performance in vitro against Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922). Antibacterial activity was assessed using the Kirby-Bauer disc diffusion method, while cytotoxicity was tested using mesenchymal stem cells. The results demonstrated that Ti-HA-CPX exhibited superior antibacterial activity, with inhibition zones of 33.5 mm (MIC 0.5 µg/mL) for Staphylococcus aureus (ATCC 25923) and 27.5 mm (MIC 0.25 µg/mL) for Escherichia coli (ATCC 25922). However, Ti-HA-CPX showed moderate cytotoxicity (80% cell viability). HACPXCS composites, whether chemically synthesized or mechanically mixed (HACPXMM), also displayed significant antibacterial activity, but with cytotoxicity ranging from low to moderate levels. Molecular docking studies confirmed strong binding affinities between ciprofloxacin and bacterial proteins, correlating with enhanced antibacterial efficacy. These findings suggest that Ti-HA-CPX composites offer a promising approach for single-stage surgical interventions in treating chronic osteomyelitis and infected fractures, balancing antibacterial effectiveness with manageable cytotoxicity.

Published
2024
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106. Comparative Analysis of Osteointegration in Hydroxyapatite and Hydroxyapatite-Titanium Implants: An In Vivo Rabbit Model Study

Author

Renata Maria Văruț, Luciana Teodora Rotaru, Flavius Nicușor Truicu, Cristina Elena Singer, Iliescu Iulian-Nicolae, Alin Iulian Silviu Popescu, Cristina Popescu, Cristina Teisanu, Gabriela Sima, and Oana Elena Nicolaescu

Subjects
bioceramic, two-steps sintering, osteointegration, Biotechnology, TP248.13-248.65, Medicine (General), R5-920
Abstract

The study evaluates the osteointegration of hydroxyapatite (HAp) and hydroxyapatite-titanium (HApTi) biocomposites implanted in the femurs of rabbits. The biocomposites were fabricated using powder metallurgy and subjected to a two-step sintering process. Scanning electron microscopy (SEM) was employed to analyze the morphology, while mesenchymal stem cells were cultured to assess cytotoxicity and proliferation. In vivo experiments involved the implantation of HAp in the left femur and HApTi in the right femur of twenty New Zealand white rabbits. Computed tomography (CT) scans, histological, immunohistochemical, and histomorphometric analyses were performed to assess bone density and osteoblast activity. Results demonstrated that HApTi implants showed superior osteointegration, with higher peri-implant bone density and increased osteoblast count compared to HAp implants. This study concluded that HApTi biocomposites have potential for enhanced bone healing and stability in orthopedic applications.

Published
2024
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107. Biological Evaluation of Balneotherapeutic Mud and Sulfurous Mineral Waters: Insights from In Vivo and In Vitro Studies

Author

Constantin Munteanu, Cristina Popescu, Diana Munteanu, Mihail Hoteteu, Madălina Gabriela Iliescu, Elena Valentina Ionescu, Liliana Stanciu, Doinița Oprea, Mihaela Minea, Carmen Oprea, Andreea Luca, Mihaela Antonina Calin, and Gelu Onose

Subjects
balneotherapy, mud, mineral waters, inflammatory markers, oxidative stress, Science
Abstract

Balneotherapy, treating diseases by bathing in mineral-rich waters and mud, has a long historical application across various cultures. Despite its widespread use, comprehensive studies on its biological impacts are scant, particularly in quantifying effects at the cellular and systemic levels. This study aims to rigorously investigate the biological effects of therapeutic mud and mineral waters, providing a scientific basis for their clinical application. We focused on elucidating the mechanisms behind the observed therapeutic effects and determining these natural resources' safety profiles. Employing a dual approach, we conducted both in vitro and in vivo studies. For the in vitro experiments, human fibroblast cells were treated with different concentrations of mud extracts to assess cytotoxicity, proliferation, and apoptosis pathways. For the in vivo assessments, Wistar rats were exposed to mud and mineral water treatments, with subsequent evaluations of biochemical markers in blood and urine indicative of systemic physiological changes. Our findings reveal that mud extracts exert a dose-dependent influence on cell viability, with low concentrations promoting cellular proliferation while higher concentrations induce apoptosis. In vivo treatments demonstrated significant modulation of inflammatory markers and oxidative stress parameters without evident systemic toxicity. The therapeutic mud and mineral waters demonstrate pronounced biological effects, enhancing cellular health and modulating systemic physiological responses without adverse side effects.

Published
2024
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108. ORAL MANIFESTATIONS IN THE MOST COMMON PEDIATRIC INFECTIOUS DISEASES

Author

Ana Maria Sciuca, Bianca-Andreea Onofrei, Corina Alexandra Concita, Mihaela-Paula Toader, Victor-Vlad Costan, and Cristina Popa

Subjects
pediatric oral lesions, herpes simplex virus, varicella, hand, foot and mouth disease, herpangina, rubeola, rubella, scarlet fever, Dentistry, RK1-715
Abstract

Childhood viral and bacterial infections may cause oral symptoms that might help early diagnosis and treatment and support the prevention efforts of pediatricians and parents. Oral lesions can clinically mimic malignancy and genetic disorders. The inflammatory changes of oral mucosa during childhood infectious diseases pose some challenges during differential diagnosis, due to the wide range of etiologies. Global migration and gaps in vaccination coverage have allowed viral infections to expand and reemerge. This review highlights the clinical features and treatment recommendations of childhood infections that can be encountered in dental practice, with a short description of the underlying systemic illness. Thorough patient history and physical examination are essential for determining the infectious agent that affects oral cavity. Treatment strategies customized for the pediatric age group are guiding the management of oral and perioral lesions from infancy through adolescence. The clinical features, diagnosis criteria, and treatment algorithms of the most common pediatric infectious diseases are summarized based on their prevalence. Dentists can play an important role in early identification of various childhood infections through soft tissue lesion investigation. Due to the numerous oral complications, vaccination awareness is another important task assigned to dentists

Published
2023

109. Considerations regarding the evolution, distribution and dynamics of the romanian football (League I) between 1989 - 2016

Author

Grigore Vasile HERMAN, Sorin D. BUHAȘ, Lucian STANCE, and Anca-Cristina POP

Subjects
lcsh:Sports, football, lcsh:GV557-1198.995, lcsh:G, lcsh:Geography. Anthropology. Recreation, League I, sports, football dynamics
Abstract

The present study aims to highlight different issues related to: the evolution, repartition and dynamics of the Romanian football (League I) between 1989 – 2016 by using an analytical approach, from singular to particular, from the team (seen as a basic cell in football) to location, county, development regions, historical region and country (seen as administrative units that support football). The importance of the study emerges from the explanatory and logical approach, from the mechanisms that contributed to the development and consolidation of the Romanian football (League I), in close correlation with the postcommunist socio-economic transformations which have defined each administrative unit involved as part of the Romanian national state.

Published
2016

110. Częściowe usunięcie przytarczyc versus całkowite usunięcie przytarczyc z autoprzeszczepem we wtórnej nadczynności przytarczyc — jednoośrodkowe, prospektywne badanie w grupie 43 pacjentów

Author

Radu Mircea Neagoe, Cristina Pop Radu, Mircea Mureșan, Septimiu Voidazan, Ionela Pașcanu, and Daniela Sala

Subjects
Parathyroidectomy, endocrine system, medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Total parathyroidectomy, 030204 cardiovascular system & hematology, medicine.disease, Surgery, Subtotal Parathyroidectomy, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Hypoparathyroidism, Refractory, 030220 oncology & carcinogenesis, medicine, Secondary hyperparathyroidism, business, Prospective cohort study, Dialysis
Abstract

Introduction: The need for parathyroidectomy remains high in the group of patients on long-term dialysis with medically refractory secondary hyperparathyroidism (sHPT). We aim to compare the results after subtotal parathyroidectomies (sPtx) and total parathyroidectomies with autotransplant (tPtx + AT) performed for sHPT at a single referral centre. Material and methods: This prospective study comparatively analysed sPtx and tPtx + AT performed in our department between February 2010 and December 2014. We followed-up both surgical techniques, with respect to the main clinical symptoms, laboratory data, mortality, and recurrent disease. Results: Forty-three patients on whom we performed 26 sPtx and 19 tPtx + AT were entered in the study. There were no statistically significant differences between groups as far as demographic and preoperative clinical data are concerned. We did not encounter postoperative mortality in either of the groups. The follow-up period was significantly longer for the sPtx group (p = 0.04). The immediate postoperative serum calcium levels were significantly lower in the tPtx + AT group (p = 0.009). Definitive hypoparathyroidism was encountered in two patients in the sPtx group (8.3%) and in one from the tPtx + AT group (5.26%). Four patients from the sPtx group (16.6%) and three from the tPtx + AT group (15.78%) died during the follow-up due to causes unrelated to parathyroidectomy. Overall we had two recurrences in the sPtx group and none in the tPtx + AT group (p = 0.57). Conclusions: In our opinion both techniques have comparable results concerning the clinical and laboratory outcomes and rates of postoperative hypoparathyroidism, at least in short- and medium-term follow-up. (Endokrynol Pol 2016; 67 (2): 202–209)

Published
2016

111. Protective Effects of a Discontinuous Treatment with Alpha-Lipoic Acid in Obesity-Related Heart Failure with Preserved Ejection Fraction, in Rats

Author

Benjamin Lauzier, Adrian Florin Gal, Cristina Mogoșan, Cristina Pop, Luc Rochette, L. Stoicescu, Béla Kiss, Steliana Ghibu, Dana-Maria Muntean, Felicia Loghin, Claudiu Morgovan, and Maria-Georgia Ștefan

Subjects
heart failure with preserved ejection fraction, 0301 basic medicine, obesity, medicine.medical_specialty, Physiology, medicine.drug_class, Clinical Biochemistry, Diastole, Hemodynamics, 030204 cardiovascular system & hematology, medicine.disease_cause, Biochemistry, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Natriuretic peptide, oxidative stress, Molecular Biology, Ejection fraction, Adiponectin, business.industry, alpha-lipoic acid, lcsh:RM1-950, Cell Biology, medicine.disease, lcsh:Therapeutics. Pharmacology, antioxidants, 030104 developmental biology, Endocrinology, Heart failure, business, Heart failure with preserved ejection fraction, Oxidative stress
Abstract

Obesity induces hemodynamic and humoral changes that are associated with functional and structural cardiac remodeling, which ultimately result in the development of heart failure (HF) with preserved ejection fraction (HFpEF). In recent years, pharmacological studies in patients with HFpEF were mostly unsatisfactory. In these conditions, alternative new therapeutic approaches are necessary. The aim of our study was (1) to assess the effects of obesity on heart function in an experimental model and (2) to evaluate the efficacy of an alpha-lipoic acid (ALA) antioxidant treatment. Sprague-Dawley rats (7 weeks old) were either included in the control group (n = 6) or subjected to abdominal aortic banding (AAB) and divided into three subgroups, depending on their diet: standard (AAB + SD, n = 8), hypecaloric (AAB + HD, n = 8) and hypercaloric with discontinuous ALA treatment (AAB + HD + ALA, n = 9). Body weight (BW), glycemia, echocardiography parameters and plasma hydroperoxides were monitored throughout the study. After 36 weeks, plasma adiposity (leptin and adiponectin) and inflammation (IL-6 and TNF-alpha) markers, together with B-type natriuretic peptide and oxidative stress markers (end-products of lipid peroxidation and endogenous antioxidant systems) were assessed. Moreover, cardiac fiber diameters were measured. In our experiment, diet-induced obesity generated cardiometabolic disturbances, and in association with pressure-overload induced by AAB, it precipitated the onset of heart failure, cardiac hypertrophy and diastolic dysfunction, while producing a pro-oxidant and pro-inflammatory plasmatic status. In relationship with its antioxidant effects, the chronic ALA-discontinuous treatment prevented BW gain and decreased metabolic and cardiac perturbations, confirming its protective effects on the cardiovascular system.

Published
2020

112. A META-ANALYSIS OF SHORT-TERM CASE-FATALITY RATE AMONG WHITE AND BLACK WOMEN WITH ACUTE CORONARY SYNDROMES

Author

Jiayi Ni, Lars Wallentin, Joanna Bryan, Abdulhalim Kinsara, Khalid AlHabib, Robert Joel Goldberg, Shamanna Iyengar, Hanh Nguyen, Corina Grey, Lu Hou Tee, Cohen Gali, Sabin Filimon, Yariv Gerber, Chiara Betoncello, Shao-Li Wang, Rathod Krishnaraj, John A. Spertus, Genovefa Kolovou, Cristina Pop, Ayman Hammoudeh, Thao Huynh, Jorge Yarzebski, Elena Guadano, and Daniel Jones

Subjects
Black women, Pediatrics, medicine.medical_specialty, White (horse), business.industry, Meta-analysis, Case fatality rate, Medicine, Cardiology and Cardiovascular Medicine, business, Term (time)
Abstract

It remains unclear whether black and white women with acute coronary syndromes (ACS) have similar short-term mortality. We completed a meta-analysis comparing the short-term mortality of black women to white women with ACS. We completed an extensive literature search from January 1987 to February

Published
2020

113. An interview with the director of biomedical informatics at Stanford

Author

Billy Rathje and Cristina Pop

Subjects
Clinical Practice, Engineering, business.industry, Field (Bourdieu), Pharmacogenomics, General Earth and Planetary Sciences, business, Data science, Health informatics, General Environmental Science
Abstract

Russ Altman discusses how computational biology is rapidly transforming clinical practice, particularly in his own field of pharmacogenomics.

Published
2015

114. Course Material Design Using the New Technologies in Language for Specific Purposes Teaching and Learning

Author

Mirela-Cristina Pop

Subjects
Engineering, Multimedia, Emerging technologies, business.industry, Foreign language teaching and learning, Material Design, computer.software_genre, Field (computer science), Course (navigation), Language for specific purposes, Engineering management, Material structure, Educational resources, ComputingMilieux_COMPUTERSANDEDUCATION, General Materials Science, French specialised language, Course material design, business, Language industry, computer, New technologies
Abstract

The study aims to present a course material design of a French specialized language developed using the new technology resources, as part of a distance study program in the field of civil engineering. The course was designed as a learning tool of French for specific purposes in the technical universities. The study presents the theoretical and methodological approach that was founded on the development of the course, the course material structure, the proposed educational resources, traditional and electronic, to meet educational objectives, the importance of using technical means of information and communication in order to improve the foreign language teaching and learning.

Published
2015

115. Snow cover in support of development of winter tourism activities in Muntele Băișorii resort

Author

Ovidiu GACEU, Luca ZARRILLI, Maria GOZNER, and Anca-Cristina POP

Subjects
parameters, lcsh:Sports, lcsh:GV557-1198.995, touristic activities, Muntele Băișorii, lcsh:G, lcsh:Geography. Anthropology. Recreation, snow cover, winter, ski
Abstract

The paper presents the characteristics of snow cover in Muntele Băişorii resort expressed on the basis of analyzing the data from meteorological observation from Băişoara station during 1961-2007 and processed on the basis of classic methodology used in climatological studies. Analyzing the values of the main parameters characterizing the snow cover was found that it enables and promotes winter tourism activities, that is why we have proposed new types of winter tourist activities such as ski touring, which would help diversify and increase the tourist flow in the resort.

Published
2015

116. Evolution of Antimicrobial Resistance in Klebsiella pneumoniae over 3 Years (2019–2021) in a Tertiary Hospital in Bucharest, Romania

Author

Alexandra Cireșă, Daniela Tălăpan, Carmen-Cristina Vasile, Cristina Popescu, and Gabriel-Adrian Popescu

Subjects
multidrug-resistant Klebsiella pneumoniae, carbapenem-resistant Klebsiella pneumoniae, risk factors for antimicrobial resistance, Therapeutics. Pharmacology, RM1-950
Abstract

Background: The antimicrobial resistance (AMR) of Klebsiella pneumoniae recorded a steep upward trend over the last two decades, among which carbapenem-resistant Klebsiella pneumoniae (CRKP) is one of the most concerning strains considering the development and spread of AMR. The aim of this study was to analyze the evolution of AMR for Klebsiella pneumoniae and to describe the risk factors of AMR for Klebsiella pneumoniae, including the COVID-19 pandemic. Methods: We conducted a retrospective study on Klebsiella pneumoniae non-duplicative isolates collected from patients admitted to a tertiary hospital in Bucharest, Romania, from January 2019 to December 2021. We evaluated AMR changes by comparing resistance between 2019 and the mean of 2020–2021. Results: The rates of AMR increased for third-generation cephalosporins, carbapenems, aminoglycosides, fluoroquinolones, and colistin and decreased for trimethoprim/sulfamethoxazole (TMP/SMX), 45.7% in 2019 vs. 28.3% in 2021. A longer length of hospital stay (ꭓ2 = 49.68, p < 0.01); recent antibiotic consumption, RR = 1.38, 95% CI [1.21, 1.57]; and recent contact with hospital settings, RR = 1.54, 95% CI [1.32, 1.8] were risk factors for multidrug-resistant (MDR) Klebsiella pneumoniae. Conclusions: The AMR of Klebsiella pneumoniae increased during 2020–2021 for most of the potential active antibiotics; only TMP/SMX resistance decreased, and it may represent a treatment option for CRKP or MDR Klebsiella pneumoniae infections. Decreasing the excessive use of antibiotics and the implementation of prevention and control measures in healthcare settings are mandatory for avoiding further increases in the AMR rate of Klebsiella pneumoniae.

Published
2024
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117. Integrative Approaches for the Diagnosis and Management of Erosive Oral Lichen Planus

Author

Cristina Popa, Ana Maria Sciuca, Bianca-Andreea Onofrei, Stefan Toader, Oana Mihaela Condurache Hritcu, Cristina Boțoc Colac, Elena Porumb Andrese, Daciana Elena Brănișteanu, and Mihaela Paula Toader

Subjects
erosive oral lichen planus, physiopathology, diagnosis, dermoscopy, topical corticosteroids, systemic immunosuppressants, Medicine (General), R5-920
Abstract

Erosive oral lichen planus (EOLP) represents a significant challenge in dental and medical management due to its chronic inflammatory nature, painful symptoms, and impact on quality of life. This study aims to evaluate the current diagnostic approach with novel non-invasive techniques, such as dermoscopy, and also the landscape of treatment options for EOLP, focusing on its efficacy, safety, and the challenges that it present in clinical practice. Through a comprehensive literature review, we explored the use of topical corticosteroids, systemic immunosuppressants, biologics, and Janus kinase (JAK) inhibitors in treating EOLP, alongside examining patient compliance, psychological impacts, and the risk of adverse effects and recurrence. Our findings reveal that while topical corticosteroids are the cornerstone of EOLP treatment, offering symptomatic relief, their long-term use is limited by side effects and tolerance development. Systemic therapies and biologics provide alternatives for refractory cases but necessitate careful adverse effect monitoring. JAK inhibitors show promise as an innovative treatment avenue but require more evidence on long-term safety and efficacy. This study highlights the necessity of personalized treatment approaches due to the variable disease course and response to treatment, underscoring the importance of a multidisciplinary strategy in managing EOLP. The complexity of EOLP treatment, compounded by its psychological and quality of life impacts, demands ongoing research into targeted therapies, the establishment of standardized treatment protocols, and the development of effective outcome measures to improve patient care and treatment outcomes.

Published
2024
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118. Ledderhose Disease: a synthetic overview of a rare medical condition and the role of physical therapy in a clinical case presentation

Author

Ioana Andone, Alexandra Cocolos, Ioana Elisei, Aura Spînu, Cristina Popescu, Alina Ciocoi, Cristina Daia, and Gelu Onose

Subjects
rehabilitation program, ledderhose disease, plantar fibromatosis, rare disease, Science
Abstract

Introduction: Ledderhose disease (LD), a rare and benign pathology, manifests in the thickening of the plantar aponeurosis, leading to the development of nodules on the plantar surfaces. First stages typically feature painless nodules, but progression may result in discomfort or pain at-tributed to inflammatory and irritating processes. Also known as plantar fibromatosis (PF), this condition is part of a spectrum of pathologies characterized by hyperproliferation of fibrous connective tissue, similar to Dupuytren contracture (palmar fibromatosis). Given that this pathology is relatively unknown but potentially disabling, we consider it im-portant to review this condition in order to manage possible complications and to expand the rehabilitation treatment, currently limited to a few physiotherapy procedures. Materials and methods: This paper presents the case of a 66-year-old patient known to have Ledderhose disease diagnosed in 2003, Dupuytren contracture of bilateral hands, osteopenia, invasive ductal carcinoma surgically treated and followed by chemotherapy and radiotherapy (2018). The patient presented to our clinic complaining of bilateral plantar pain, with the left side exhibiting greater severity, accompanied by paresthesia in a sock-like distribution and dif-ficulty with ambulation. On clinical examination, bilateral flatfoot deformity, stage 1 Dupuytren contracture of the bilateral palmar aponeurosis, mildly reduced distal muscle strength in both upper and lower extremities and plantar synovial cysts were noted, findings that were subsequently confirmed via MRI imaging. The physiotherapeutic plan was designed to reduce symptomatic manifestations, attenuate the inflammatory cascade and optimize gait pattern. However, considering the patient's medical history, we were limited in prescribing physiotherapy procedures. The patient was dynamically evaluated using the following scales: Visual analogue scale (VAS), Life Quality Assessment (QOL), The Functional Ambulation Categories (FAC), Index of Inde-pendence in Activities of Daily Living (ADL) and Medical Research Council Scale for muscle strength (MRC). Results: Considering the associated oncological pathology, our ability to prescribe physiother-apy procedures was constrained. However, the patient benefited from an individualized reha-bilitation program specific to the pathology with a favorable evolution and a promising prog-nosis. The program included physical therapy sessions targeting stretching, toning and en-hancing muscle strength for the plantar and palmar muscle groups, alongside paraffin applica-tions, low-frequency current (Transcutaneous Electrical Nerve Stimulation - TENS) and Deep oscillation applications. Conclusions: The complex rehabilitation approach in a patient with a rare medical condition, complicated with degenerative diseases, though limited in variety due to associated oncologi-cal pathology contributed in the end to a significant improvement of the patient's quality of life.

Published
2024
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119. Long-term case management and outcomes in a young male patient with complete paraplegia post T4-T5 vertebral osteomyelitis and a previous documented thalamo-mesencephalic hemorrhage – case presentation

Author

Roxana Bistriceanu, Aura Spînu, Cristina Daia, Ioana Andone, Cristina Popescu, Mihai Băilă, Ruxandra Postoiu, and Gelu Onose

Subjects
paraplegia, vertebral osteomyelitis, neurorehabilitation, Science
Abstract

(1) Background: Vertebral osteomyelitis is an infection affecting the vertebrae, with a poten-tially devastating impact, which requires a prompt diagnosis established as quickly as possible to avoid complications such as neurological impairment, fractures, and chronic pain; (2) Meth-ods: We reported a case of a 47-year-old male patient with multiple risk factors (high blood pressure, smoking, dyslipidemia, type II diabetes) and a history of right hemiplegia post a thalamo- mesencephalic hemorrhage, admitted to the Neuromuscular Clinic Division of The Teaching Emergency Hospital “Bagdasar- Arseni” (TEHBA) Bucharest, for complete paraplegia following a surgically treated vertebral osteomyelitis at T4-T5 level with spinal epidural ab-scess; (3) Results: The patient had an oscillating and long evolution, due to long-term antibio-therapy and the imperative of minimal mobilization periods, which eventually led to favorable results, with the recovery of motor function and the ability to perform his previous daily activ-ities; (4) Conclusions: Proper management in vertebral osteomyelitis cases has a great impact on the evolution of the patient, increasing the quality of life, and preventing future complica-tions. A multidisciplinary approach is essential for this type of complex case in order to achieve significant improvements

Published
2024
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120. Protective Effects of Hesperetin on Cardiomyocyte Integrity and Cytoskeletal Stability in a Murine Model of Epirubicin-Induced Cardiotoxicity: A Histopathological Study

Author

Adina Pop Moldovan, Simona Dumitra, Cristina Popescu, Radu Lala, Nicoleta Zurbau Anghel, Daniel Nisulescu, Ariana Nicoras, Coralia Cotoraci, Monica Puticiu, Anca Hermenean, and Daniela Teodora Marti

Subjects
epirubicin, hesperetin, cardiac toxicity, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract

Anthracyclines, including epirubicin (Epi), are effective chemotherapeutics but are known for their cardiotoxic side effects, primarily inducing cardiomyocyte apoptosis. This study investigates the protective role of hesperetin (HSP) against cardiomyopathy triggered by Epi in a murine model. Male CD1 mice were divided into four groups, with the Epi group receiving a cumulative dose of 12 mg/kg intraperitoneally, reflecting a clinically relevant dosage. The co-treatment group received 100 mg/kg of HSP daily for 13 days. After the treatment period, mice were euthanized, and heart tissues were collected for histopathological, immunofluorescence/immunohistochemistry, and transmission electron microscopy (TEM) analyses. Histologically, Epi treatment led to cytoplasmic vacuolization, myofibril loss, and fiber disarray, while co-treatment with HSP preserved cardiac structure. Immunofluorescent analysis of Bcl-2 family proteins revealed Epi-induced upregulation of the pro-apoptotic protein Bax and a decrease in anti-apoptotic Bcl-2, which HSP treatment reversed. TEM observations confirmed the preservation of mitochondrial ultrastructure with HSP treatment. Moreover, in situ detection of DNA fragmentation highlighted a decrease in apoptotic nuclei with HSP treatment. In conclusion, HSP demonstrates a protective effect against Epi-induced cardiac injury and apoptosis, suggesting its potential as an adjunctive therapy in anthracycline-induced cardiomyopathy. Further studies, including chronic cardiotoxicity models and clinical trials, are warranted to optimize its therapeutic application in Epi-related cardiac dysfunction.

Published
2024
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121. CARDIOMETABOLIC DISORDERS AND ENDOTOXEMIA IN THE CONTEXT OF PERIODONTITIS – THE IMPORTANCE OF METABOLOMICS. A NARRATIVE REVIEW

Author

Maria–Alexandra Martu, Liliana Pasarin, Ana-Maria Sciuca, Cristina Popa, George-Alexandru Maftei, Ovidiu Nicolaiciuc, Oana Butnaru, Ruxandra Stan, Silvia Martu, and Ionut Luchian

Subjects
periodontitis, cardiometabolic disorders, endotoxemia, metabolomics, Dentistry, RK1-715
Abstract

Periodontitis patients are known to have increased circulating lipopolysaccharide activity and metabolic disturbances, which may be either the cause or effect of endotoxemia. This review approaches endotoxemia as a possible molecular mediator between periodontitis and increased risk of cardiometabolic disorders. Observations that bacteria disseminate into circulation after toothbrushing and periodontal procedures and assumptions that endotoxin may disseminate through inflamed periodontium and bleeding gums support the idea of endotoxemia in periodontitis. However, the evidence that periodontitis-associated dysbiosis contributes to endotoxemia is not as strong as in the case of gut microbiome dysbiosis. Although the causality is insufficiently demonstrated thus far, many studies have associated changes of the gut microbiome composition, function, and specific bacterial metabolites with cardiometabolic diseases, whereas research on the oral microbiome has severely fallen behind.

Published
2022

122. ROLE OF LIPOPOLYSACCHARIDES AND ENDOTOXEMIA IN PERIODONTITIS. A NARRATIVE REVIEW

Author

Liliana Pasarin, Maria-Alexandra Martu, Ancuta Goriuc, Cristina Popa, Odette Luca, Irina–Georgeta Sufaru, Ruxandra Stan, Silvia Martu, and Ionut Luchian

Subjects
periodontitis, cardiometabolic disorders, lipopolysaccharide and endotoxemia, Dentistry, RK1-715
Abstract

Periodontitis patients are known to have increased circulating lipopolysaccharide activity and metabolic disturbances, which may be either the cause or effect of endotoxemia. This review approaches endotoxemia as a possible molecular mediator between periodontitis and increased risk of cardiometabolic disorders. Observations that bacteria disseminate into circulation after toothbrushing and periodontal procedures and assumptions that endotoxin may disseminate through inflamed periodontium and bleeding gums support the idea of endotoxemia in periodontitis. However, the evidence that periodontitis-associated dysbiosis contributes to endotoxemia is not as strong as in the case of gut microbiome dysbiosis. We describe the structure-function relationship of lipopolysaccharide, the local and systemic inflammatory and immunological responses caused by lipopolysaccharide, current knowledge on endotoxemia in periodontitis, factors affecting the levels of endotoxemia, and its relation to cardiometabolic disorders. They are physically, microbiologically, and biochemically connected to each other, and only crumbs of information are known about this connection. Although the causality is insufficiently demonstrated thus far, many studies have associated changes of the gut microbiome composition, function, and specific bacterial metabolites with cardiometabolic diseases, whereas research on the oral microbiome has severely fallen behind.

Published
2022

123. HEMATOLOGICAL PATHOLOGY BETWEEN DIAGNOSIS AND TREATMENT IN THE CONTEXT OF ORAL MANIFESTATIONS. MANAGEMENT OF THE PATIENT WITH LEUKEMIA IN THE DENTAL PRACTICE. REVIEW

Author

Maria-Alexandra Martu, Oana Ciurcanu, George-Alexandru Maftei, Liliana Pasarin, Cristina Popa, Darius Sandu, Oana Butnaru, and Ionut Luchian

Subjects
oral disease, periodontal disease, leukemia, management therapeutic, Dentistry, RK1-715
Abstract

Periodontal pathology and early clinical manifestations in the context of leukemia are influenced by the host organism, by immunological, microbiological and genetic factors, but also by environmental factors (physical agents (ionizing radiation, x-rays) and chemical agents (drugs such as cytostatics, exposure to organic solvents or to pesticides, herbicides, exposure to cigarette smoke). The purpose of this article is to emphasize both the importance of the health status of the marginal periodontium and the severity of gingival-periodontal manifestations in the context of haematological diseases. We also want to draw attention to the role of periodontal treatment: the elimination of periodontal inflammation, the reduction of periodontal pockets, the maintenance of rigorous oral hygiene and the periodic check-up in a dental practice in this category of patients. Clinical and radiological evidence-gathering is very important in the recognition and diagnosis of gingival-periodontal manifestations in haematological diseases, as when they are not treated in time, they become a source of infection of the oral cavity and in the entire body. Conclusions. It is essential to analyze this interaction in all aspects, from a clinical, microbiological, immunological and genetic point of view, in order to make a diagnosis and implement a correct and complete treatment plan.

Published
2022

124. AUTOMATION SYSTEM OF A MANEUVERING OPERATION WITHIN A DRILLING INSTALLATION

Author

Cristina Popescu and Andrei Olteanu

Subjects
drilling, automation, oil & gas, offshore oil & gas industry, Technology (General), T1-995, Science
Abstract

The Oil and Gas industry is pursuing major changes in automation, with the aim of reducing the risk involved in operations and increasing efficiency, speeding up processes to reduce costs. Internationally and especially in the Offshore environment, deposits with high productive potential are targeted, which are put into operation through a small number of wells with a high flow rate, due to the complexity of marine drilling. The high costs in this sector of the industry make it necessary to optimize all operational times, thus we very often encounter automation elements in the marine drilling process. This work intends to present the advantages of using the Simulink program package in the simulation of the processes, respectively of the maneuver operation in a drilling installation, to predict their real behavior.

Published
2022
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125. Long-term monitoring of high optical imagery of the stratospheric clouds and their properties new approaches and conclusions

Author

Aleksandar Valjarević, Cristina Popovici, Tatjana Djekić, Cezar Morar, Dejan Filipović, and Tin Lukić

Subjects
Stratosphere, Remote sensing, Geographical information systems, Cloudiness, Geodesy, QB275-343
Abstract

The investigation of weather properties and clouds distribution in the stratosphere is rare, but essential for science. In this research, twenty years of satellite recordings showed the properties of stratospheric clouds approved by GIS (Geographical Information System) and Remote sensing (RS) techniques. This type of clouds covered a small area in the analyzed period, but the results were important for meteorological and climatological condition in the atmosphere. A very tiny layer of water vapor and their low concentration produces a small number of clouds throughout the year. The average altitude of the stratosphere varied between 12 km and 50 km. The stratosphere is very dry; only polar stratospheric clouds (PSCCl) may be found. This type of clouds appears near the poles in the winter season. This research provides the explanation on the climate properties of clouds (water content) in this layer of the atmosphere. The layers of this type of clouds present stable factor of meteorological stability, but have recently been influenced by climate change effects. The new findings of water in the stratosphere were made possible by precise analysis of satellite recordings. The estimated amount of water in the clouds in the stratosphere may be significant for potential cloud seeding in the future.

Published
2022
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126. SKI LEARNING DIFFICULTIES OF DIFFERENT SPORT ATHLETES.

Author

BARNA, SZABÓ-CSIFÓ and CRISTINA, POP ALEXANDRA

Subjects
WINTER sports, SPORTS competitions, PRACTICE (Sports), LEISURE, ATHLETES, POINTING (Gesture)
Abstract

Copyright of Studia Universitatis Babes-Bolyai, Educatio Artis Gymnasticae is the property of Babes-Bolyai University, Cluj-Napoca, Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2020
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127. A conversation with Vijay Pande

Author

Cristina Pop

Subjects
Computer science, Human–computer interaction, media_common.quotation_subject, General Earth and Planetary Sciences, Conversation, General Environmental Science, Connection (mathematics), media_common
Abstract

The director of Stanford University's Pande Lab discusses how his work with large-scale, distributed simulation is being used to study protein folding and its connection to disease.

Published
2015

128. Cloudiness and water from cloud seeding in connection with plants distribution in the Republic of Moldova

Author

Aleksandar Valjarević, Cristina Popovici, Anđelka Štilić, and Milan Radojković

Subjects
Cloudiness, Remote sensing, GIS, Republic of Moldova, Alternative water, Cloud seeding, Water supply for domestic and industrial purposes, TD201-500
Abstract

Abstract Clouds play an important role in maintaining the balance in the environment. Cloudiness can influence numerous important ecological drivers, including growth, survival and distribution of plants. The cloud cover dynamics and distribution may provide key information for delineating various types of plant and species distribution. During a year, different types of clouds on a territory can influence the distribution of plants and potential of cloud seeding. New properties of cloudiness may be important for new ecological patterns and new adapted values of ecological drivers. In the territory of the Republic of Moldova, 30 years of cloudiness were taken to show new distribution of clouds properties and their influence on sunflower (Helianthus annus L.) and grapes (Vitis vinifera). The main result of this research is the first established map with the location of water derived from cloud seeding. In the last decade (2010–2020), the cloudiness increased by more than 15%. Another important focus of this research is the possibility of cloud seeding in line with recent deficit of precipitation, especially in dry areas. The territory of Moldova has 37% of semiarid and 6% of arid zones. The distribution and the potential of cloud seeding has been analyzed by means of Remote Sensing and GIS techniques and methodology, along with the Moderate Resolution Imaging Spectroradiometer. Satellite data in the resolution of 1 km2 were downloaded for the period between 1990 and 2020. The exact distribution of clouds helped to determine the belts for the potential irrigation of crops. Extremely low cloudiness and a long period of drought may jeopardize the agricultural sector in the Republic of Moldova, and therefore, the irrigation from alternative water sources is of utmost importance.

Published
2022
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129. ARE PERIODONTAL TISSUES AND PERIODONTAL HEALTH IMPACTED BY FOOD SUPPLEMENTS (PROTEIN AND AMINOACIDS, NATURAL HERBAL PRODUCTS, MINERALS)? – REVIEW

Author

George Alexandru Maftei, Oana Ciurcanu, Odette Luca, Liliana Pasarin, Cristina Popa, Mihaela Mares, Maria Alexandra Martu, and Ionut Luchian

Subjects
food supplements, periodontal tissues, prevention or treatment of periodontal diseases, Dentistry, RK1-715
Abstract

The aim of this review is to provide an overview of the current evidence of some popular food supplements and superfoods that might be of interest in periodontology. Although the number of publications investigating the effect of these products on human health and their possible use in medicine is increasing, only little is known so far regarding their effects on periodontal tissues and their possible use in periodontal treatment or medicine. In summary, an increasing number of studies have revealed aspects and effects of these so-called lifestyle or fitness supplements and superfoods that may have an impact on periodontal health and healing after treatment. However, some the current evidence is of a very low quality, and more validated scientific data are required before their possible use in prevention or treatment of periodontal diseases can be made.

Published
2022

130. INFLUENCE OF FISH OIL/OMEGA-3 FATTY ACIDS FOOD SUPPLEMENTS ON PERIODONTAL TISSUES AND HEALTH. A NARRATIVE REVIEW

Author

Maria Alexandra Martu, Luchian Ionut, Oana Ciurcanu, Odette Luca, Mihaela Mares, Liliana Pasarin, Cristina Popa, and Ioana Martu

Subjects
food supplements, omega-3 fatty acids, periodontal tissues, prevention or treatment of periodontal diseases, Dentistry, RK1-715
Abstract

Introduction. As the area of nano-based platforms for antimicrobial treatment aimed at pathogenic oral biofilms continues to expand, this review serves to bring together researchers from several disciplines to foster more collaboration and discovery among dental practitioners.

Published
2022

133. Predicting the unemployment rate and energy poverty levels in selected European Union countries using an ARIMA-ARNN model

Author

Claudiu Ionut Popirlan, Irina-Valentina Tudor, and Cristina Popirlan

Subjects
Forecasting, Time series, Developing/developed countries, Hybrid model, ARIMA-ARNN, Electronic computers. Computer science, QA75.5-76.95
Abstract

This article analyzes the correlation between energy poverty percentage and unemployment rate for four European countries, Bulgaria, Hungary, Romania and Slovakia, comparing the results with the European average. The time series extracted from the datasets were imported in a hybrid model, namely ARIMA-ARNN, generating predictions for the two variables in order to analyze their interconnectivity. The results obtained from the hybrid model suggest that unemployment rate and energy poverty percentage have comparable tendencies, being strongly correlated. The forecasts suggest that this correlation will be maintained in the future unless appropriate governmental policies are implemented in order to lower the impact of other aspects on energy poverty.

Published
2023
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134. Determination of Ozone Concentration Levels in Urban Environments Using a Laser Spectroscopy System

Author

Mioara Petrus, Cristina Popa, and Ana-Maria Bratu

Subjects
ambient air, pollution, ozone, photoacoustic spectroscopy, Environmental technology. Sanitary engineering, TD1-1066
Abstract

In urban areas, there has been a recent rise in ground-level ozone. Given its toxicity to both humans and the environment, the investigation of ozone pollution demands attention and should not be overlooked. Therefore, we conducted a study on ozone concentration in three distinct locations within the city of Magurele, Romania. This investigation considered variations in both structure and location during the spring and summer seasons, specifically at a breathing level of 1.5 m above the ground. Our analysis aimed to explore the impact of different locations and meteorological variables on ozone levels. The three measurement points were strategically positioned in diverse settings: within the city, in a forest, and within an industrial area. For these measurements, we used a laser spectroscopy system to determine the system’s sensitivity and selectivity and the influence of humidity in the detection of ozone in ambient air, which is a mixture of trace gases and water vapor. During the March–August campaign, the mean values in the three measuring points were 24.45 ± 16.44 ppb, 11.96 ± 3.80 ppb, and 95.01 ± 37.11 ppb. The peak concentrations of ozone were observed during the summer season. A diurnal analysis revealed that the atmospheric ozone levels were higher in the latter part of the day compared to the earlier part. These measurements suggest that the atmospheric temperature plays a significant role in tropospheric ozone production. Additionally, meteorological variables such as wind speed and direction were found to influence the ozone concentration. Remarkably, despite substantial traffic, the ozone levels remained consistently low throughout the entire period within the forested area. This observation may suggest the remarkable ability of trees to mitigate pollution levels.

Published
2024
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135. Children with autism social engagement in interaction with Nao, an imitative robot

Author

Alina S. Rusu, Amir Aly, Andreea Peca, Adriana Tapus, Lavinia Jisa, Cristina Pop, Sebastian Pintea, Daniel David, ALY, Amir, Unité d'Informatique et d'Ingénierie des Systèmes (U2IS), École Nationale Supérieure de Techniques Avancées (ENSTA Paris), Babes-Bolyai University [Cluj-Napoca] (UBB), Robotique et Vision (RV), and École Nationale Supérieure de Techniques Avancées (ENSTA Paris)-École Nationale Supérieure de Techniques Avancées (ENSTA Paris)

Subjects
0209 industrial biotechnology, Linguistics and Language, media_common.quotation_subject, autism, 02 engineering and technology, Language and Linguistics, Human–robot interaction, Developmental psychology, Laughter, human-robot interaction, 020901 industrial engineering & automation, medicine, [INFO.INFO-RB]Computer Science [cs]/Robotics [cs.RO], 0501 psychology and cognitive sciences, media_common, assistive robotics, Communication, [INFO.INFO-RB] Computer Science [cs]/Robotics [cs.RO], 05 social sciences, technology, industry, and agriculture, Social engagement, medicine.disease, Gaze, body regions, Human-Computer Interaction, surgical procedures, operative, Eye tracking, Autism, Robot, Animal Science and Zoology, Psychology, Imitation, human activities, 050104 developmental & child psychology
Abstract

This paper presents a series of 4 single subject experiments aimed to investigate whether children with autism show more social engagement when interacting with the Nao robot, compared to a human partner in a motor imitation task. The Nao robot imitates gross arm movements of the child in real-time. Different behavioral criteria (i.e. eye gaze, gaze shifting, free initiations and prompted initiations of arm movements, and smile/laughter) were analyzed based on the video data of the interaction. The results are mixed and suggest a high variability in reactions to the Nao robot. The results are as follows: For Child2 and Child3, the results indicate no effect of the Nao robot in any of the target variables. Child1 and Child4 showed more eye gaze and smile/laughter in the interaction with the Nao robot compared to the human partner and Child1 showed a higher frequency of motor initiations in the interaction with the Nao robot compared to the baselines, but not with respect to the human-interaction. The robot proved to be a better facilitator of shared attention only for Child1. Keywords: human-robot interaction; assistive robotics; autism

Published
2012

136. Using the social robot probo as a social story telling agent for children with ASD

Author

Ramona Simut, Dirk Lefeber, Alina S. Rusu, Bram Vanderborght, Cristina Pop, Sebastian Pintea, Jelle Saldien, and Daniel David

Subjects
Linguistics and Language, Facial expression, Social robot, Communication, Social Stories, medicine.disease, Gaze, Language and Linguistics, Social relation, Human-Computer Interaction, Social skills, medicine, Autism, Robot, Animal Science and Zoology, Psychology, Social psychology, Cognitive psychology
Abstract

This paper aims to study the role of the social robot Probo in providing assistance to a therapist for robot assisted therapy (RAT) with autistic children. Children with autism have difficulties with social interaction and several studies indicate that they show preference toward interaction with objects, such as computers and robots, rather than with humans. In 1991, Carol Gray developed Social Stories, an intervention tool aimed to increase children’s social skills. Social stories are short scenarios written or tailored for autistic individuals to help them understand and behave appropriately in social situations. This study shows that, in specific situations, the social performance of autistic children improves when using the robot Probo, as a medium for social story telling, than when a human reader tells the stories. The robot tells Social Stories to teach ASD children how to react in situations like saying “hello”, saying “thank you” and “sharing toys”. The robot has the capability of expressing emotions and attention via its facial expressions and its gaze. The paper discusses the use of Probo as an added-value therapeutic tool for social story telling and presents the first experimental results. Keywords: social robot; ASD children; social story; robot assisted therapy

Published
2012

137. Robot-Assisted Therapy for Autism Spectrum Disorders with (Partially) Autonomous Control: Challenges and Outlook

Author

Serge Thill, Tom Ziemke, Tony Belpaeme, Cristina Pop, and Bram Vanderborght

Subjects
Shared Autonomy, Technology, Cognitive Neuroscience, media_common.quotation_subject, autism spectrum disorders, Theory of Mind, Behavioural sciences, Annan data- och informationsvetenskap, Field (computer science), robot-assisted therapy, Behavioral Neuroscience, Developmental Neuroscience, Artificial Intelligence, Human–computer interaction, Theory of mind, Medicine, Assisted therapy, media_common, theory of mind, Point (typography), business.industry, medicine.disease, Robot-Assisted Therapy, shared autonomy, Human-Computer Interaction, Autism Spectrum Disorders, Autism, Robot, business, Other Computer and Information Science, Autonomy
Abstract

Robot-assisted therapy (RAT) is an emerging field that has already seen some success and is likely to develop in the future. One particular application area is within therapies for autism spectrum disorders, in which the viability of the approach has been demonstrated.The present paper is a vision paper with the aim of identifying research directions in the near future of RAT. Specifically, we argue that the next step in such therapeutic scenarios is the development of more substantial levels of autonomy which would allow the robot to adapt to the individual needs of children over longer periods of time (while remaining under the ultimate supervision of a therapist). We argue that this requires new advances on the level of robot controllers as well as the ability to infer and classify intentions, goals and emotional states of the robot’s interactants. We show that the state of the art in a number of relevant disciplines is now at the point at which such an endeavour can be approached in earnest.

Published
2012

138. 0517 : Vascular and metabolic effect of Olea europaea leaf extract, in highcarbohydrate high-fat-fed rats

Author

Neli Olah, Claudiu Morgovan, Cristina Mogosan, Mircea Mircean, Oliviu Vostinaru, Cristina Pop, and Steliana Ghibu

Subjects
medicine.medical_specialty, biology, business.industry, C-reactive protein, medicine.disease, Malondialdehyde, medicine.disease_cause, High fat fed, Transaminase, chemistry.chemical_compound, Blood pressure, Endocrinology, chemistry, Olea europaea leaf extract, Internal medicine, medicine, biology.protein, Metabolic syndrome, business, Cardiology and Cardiovascular Medicine, Oxidative stress
Abstract

Introduction The purpose of this study was to monitor the benefits provided by Olive leaf extract in rats which present symptoms of metabolic syndrome. Methods 48 male Wistar rats were randomized into two series (n=24): rats fed for 15 weeks with standard chow (Control) and rats fed with high-carbohydrate high-fat diet (HCHF). In each series, a group of rats (n=12) was treated daily, orally with Olea europaea leaf extract, dissolved in drinking water (0.8ml vegetal extract/60ml H2O/4 rats), within 12 weeks. Body weight, glycemia and systolic blood pressure were being monitored throughout the study. At the end of the study a pulsed-wave Doppler velocity profile of the carotid artery was also recorded. After 12 weeks of diet and treatment, there were assessed: plasma lipoproteins, transaminase activities and the C reactive protein (CRP). Plasma oxidative stress was determined by the measurement of hydroperoxides, malondialdehyde and protein carbonyl groups. Results During the study the HCHF-diet induced a loss of body weight as compared with Control group. The glycaemia and the systolic blood pressure have significantly (p Conclusions In our experimental conditions, the metabolic disorders and the oxidative stress associated were ameliorated by Olea europaea leaf extract which could open the new perspectives in the adjuvant treatment of the cardiometabolic syndrome The author hereby declares no conflict of interest

Published
2016
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139. Metabolic and Other Endocrine Elements with Regard to Lifestyle Choices: Focus on E-Cigarettes

Author

Andrei Osman, Gabriel Sebastian Petrescu, Mihaela Jana Tuculină, Ionela Teodora Dascălu, Cristina Popescu, Anca-Ștefania Enescu, Constantin Dăguci, Anca-Pati Cucu, Claudiu Nistor, and Mara Carsote

Subjects
lifestyle, metabolic, endocrine disorder, diabetes, obesity, metabolic syndrome, Microbiology, QR1-502
Abstract

Our objective was to overview recent data on metabolic/endocrine disorders with respect to e-cigarette (e-cig) use. This is a narrative review; we researched English, full-length, original articles on PubMed (between January 2020 and August 2023) by using different keywords in the area of metabolic/endocrine issues. We only included original clinical studies (n = 22) and excluded case reports and experimental studies. 3 studies (N1 = 22,385; N2 = 600,046; N3 = 5101) addressed prediabetes risk; N1 showed a 1.57-fold increased risk of dual vs. never smokers, a higher risk that was not confirmed in N2 (based on self-reported assessments). Current non-smokers (N1) who were dual smokers still have an increased odd of prediabetes (a 1.27-fold risk increase). N3 and another 2 studies addressed type 2 diabetes mellitus (DM): a lower prevalence of DM among dual users (3.3%) vs. cigarette smoking (5.9%) was identified. 6 studies investigated obesity profile (4 of them found positive correlations with e-cig use). One study (N4 = 373,781) showed that e-cig use was associated with obesity in the general population (OR = 1.6, 95%CI: 1.3–2.1, p < 0.05); another (N5 = 7505, 0.82% were e-cig-only) showed that obesity had a higher prevalence in dual smokers (51%) vs. cig-only (41.2%, p < 0.05), while another (N6 = 3055) found that female (not male) e-cig smokers had higher body mass index vs. non-smokers. Data on metabolic syndrome (MS) are provided for dual smokers (n = 2): one case–control study found that female dual smokers had higher odds of MS than non-smokers. The need for awareness with respect to potential e-cig-–associated medical issues should be part of modern medicine, including daily anamnesis. Whether the metabolic/endocrine frame is part of the general picture is yet to be determined. Surveillance protocols should help clinicians to easily access the medical background of one subject, including this specific matter of e-cig with/without conventional cigarettes smoking and other habits/lifestyle elements, especially when taking into consideration metabolism anomalies.

Published
2023
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140. A Survey of Expectations About the Role of Robots in Robot-Assisted Therapy for Children with ASD: Ethical Acceptability, Trust, Sociability, Appearance, and Attachment

Author

Andreea Peca, Sebastian Pintea, Ramona Simut, Mark Coeckelbergh, Daniel David, Cristina Pop, Bram Vanderborght, Applied Mechanics, Robotics & Multibody Mechanics Research Group, and Clinical and Lifespan Psychology

Subjects
Parents, 0209 industrial biotechnology, Health (social science), Autism Spectrum Disorder, media_common.quotation_subject, 02 engineering and technology, Robot assisted therapy ASD Autism Ethics of robotics Trust Appearance Safety Therapy, Trust, 0603 philosophy, ethics and religion, 020901 industrial engineering & automation, Surveys and Questionnaires, Management of Technology and Innovation, medicine, Humans, Quality (business), Child, media_common, Philosophy of science, Responsible Research and Innovation, business.industry, Health Policy, Robotics, 06 humanities and the arts, medicine.disease, Object Attachment, Psychotherapy, Issues, ethics and legal aspects, Attitude, Autism spectrum disorder, Physical Appearance, Body, Robot, Autism, ComputingMilieux_COMPUTERSANDSOCIETY, 060301 applied ethics, Artificial intelligence, School Teachers, business, Psychology, Social psychology, Autonomy
Abstract

The use of robots in therapy for children with autism spectrum disorder (ASD) raises issues concerning the ethical and social acceptability of this technology and, more generally, about human-robot interaction. However, usually philosophical papers on the ethics of human-robot-interaction do not take into account stakeholders' views; yet it is important to involve stakeholders in order to render the research responsive to concerns within the autism and autism therapy community. To support responsible research and innovation in this field, this paper identifies a range of ethical, social and therapeutic concerns, and presents and discusses the results of an exploratory survey that investigated these issues and explored stakeholders' expectations about this kind of therapy. We conclude that although in general stakeholders approve of using robots in therapy for children with ASD, it is wise to avoid replacing therapists by robots and to develop and use robots that have what we call supervised autonomy. This is likely to create more trust among stakeholders and improve the quality of the therapy. Moreover, our research suggests that issues concerning the appearance of the robot need to be adequately dealt with by the researchers and therapists. For instance, our survey suggests that zoomorphic robots may be less problematic than robots that look too much like humans.

Published
2016

141. Competence-Based Curricular Design for Foreign Language Teaching in the Romanian Technical Universities

Author

Crisanta-Alina Mazilescu and Mirela-Cristina Pop

Subjects
Engineering, Higher education, business.industry, Competence-based curriculum, media_common.quotation_subject, Romanian, Foreign language, foreign language teaching, methodological approach, Bachelor, language.human_language, Foreign language teaching, ComputingMilieux_COMPUTERSANDEDUCATION, Mathematics education, language, General Materials Science, business, Quality assurance, Competence (human resources), technical universities, media_common
Abstract

The present article aims at describing specific types of foreign language competences tailored for engineering students enrolled in the Romanian-language-taught bachelor programmes of the Romanian technical higher education. The research subscribes to the current methodological approach of the Romanian higher education which focuses on quality assurance and prioritizes learning outcomes and the formulation of course objectives in terms of knowledge, skills and know-how.

Published
2012

142. Glycine Fluoromethylketones as SENP-Specific Activity Based Probes

Author

Cristina Pop, Gheorghe-Doru Roiban, Ioana Dumitru, Niculina D. Hădade, Guy S. Salvesen, Veronika M. Meier, Domenico Fasci, Mihaela Matache, Cristian Dobrota, and Daniel P. Funeriu

Subjects
Proteases, Binding Sites, SENP1, Chemistry, C-terminus, Organic Chemistry, Glycine, Ketones, Biochemistry, Recombinant Proteins, Protein–protein interaction, Enzyme Activation, HEK293 Cells, Endopeptidases, Humans, Molecular Medicine, Moiety, Specific activity, Binding site, Molecular Biology, Fluorescent Dyes, Cysteine
Abstract

We report here the synthesis and biochemical properties of a new peptidyl activity-based probe 1 for SUMO proteases, SENPs. The activity-based probe has at its C terminus a glycine-derived fluoromethylketone moiety as a reactive group designed to target the active-site cysteine of SENPs. Based on a study of the interactions between SENPs and SUMOs, we introduced further design elements that allow the activity-based probe to selectively target SENPs at low micromolar to high nanomolar concentrations. Moreover, 1 out-competes SUMO1 from the reversible SUMO1-SENP1 complex, thus suggesting that 1 and SUMO1 share a common binding site on SENP1.

Published
2011

143. Catalytic activity of the caspase-8-FLIPL complex inhibits RIPK3-dependent necrosis

Author

Patrick Fitzgerald, Razq Hakem, Ricardo Weinlich, Laura L. McCormick, Douglas R. Green, Andrew Oberst, Cristina Pop, Christopher P. Dillon, and Guy S. Salvesen

Subjects
0303 health sciences, Programmed cell death, Multidisciplinary, Necrosis, Necroptosis, Ripoptosome, Biology, Fas receptor, Caspase 8, Molecular biology, Article, 3. Good health, CFLAR, Cell biology, 03 medical and health sciences, 0302 clinical medicine, Apoptosis, 030220 oncology & carcinogenesis, medicine, medicine.symptom, 030304 developmental biology
Abstract

Caspase-8 mediates apoptosis induced by 'death receptors' on the cell's surface. At the same time, it is able to prevent receptor interacting protein kinase (RIPK)-dependent necrosis. Without caspase-8, mice die during embryonic development, but why this happens is not clear. Two groups show that this lethality is not caused by the absence of apoptosis, but by the RIPK3-dependent necrosis that is unleashed without caspase-8. Mice lacking both caspase-8 and RIP3 develop into viable, immunocompetent adults, but have a progressive lymphoaccumulative disease similar to that in mice that lack the CD95 death receptor. Oberst et al. also show that caspase-8 forms a proteolytically active complex with FLICE-like inhibitory protein long (FLIPL), and that this complex is required for protection against RIP3-dependent necrosis. Caspase-8 mediates apoptosis induced by death receptors. At the same time, this protease is able to prevent RIP-dependent necrosis. Without caspase-8 mice die during their embryonic development. Two papers now show that lethality is not caused by the absence of apoptosis, but by RIP3-dependent necrosis that is unleashed without caspase-8. Mice that lack both caspase-8 and RIP3 develop into viable, immunocompetent, fertile adult mice, but suffer from a progressive lymphoaccumulative disease similar to mice that lack the death receptor CD95. This paper further shows that caspase-8 forms a proteolytically active complex with FLIPL, and that this complex is required for protection against RIP3-dependent necrosis. Caspase-8 has two opposing biological functions—it promotes cell death by triggering the extrinsic pathway of apoptosis, but also has a survival activity, as it is required for embryonic development1, T-lymphocyte activation2, and resistance to necrosis induced by tumour necrosis factor-α (TNF-α) and related family ligands3,4. Here we show that development of caspase-8-deficient mice is completely rescued by ablation of receptor interacting protein kinase-3 (RIPK3). Adult animals lacking both caspase-8 and RIPK3 display a progressive lymphoaccumulative disease resembling that seen with defects in CD95 or CD95-ligand (also known as FAS and FASLG, respectively), and resist the lethal effects of CD95 ligation in vivo. We have found that caspase-8 prevents RIPK3-dependent necrosis without inducing apoptosis by functioning in a proteolytically active complex with FLICE-like inhibitory protein long (FLIPL, also known as CFLAR), and this complex is required for the protective function.

Published
2011

144. FLIPL induces caspase 8 activity in the absence of interdomain caspase 8 cleavage and alters substrate specificity

Author

Douglas R. Green, Guy S. Salvesen, Marcin Drag, Bram J. van Raam, Andrew Oberst, Stefan J. Riedl, and Cristina Pop

Subjects
Fas-Associated Death Domain Protein, Caspase 2, CASP8 and FADD-Like Apoptosis Regulating Protein, Apoptosis, Caspase 3, Caspase 8, Biochemistry, Article, Substrate Specificity, Mice, Animals, Molecular Biology, Caspase, Death domain, Mice, Knockout, biology, NLRP1, Hydrolysis, Cell Biology, Molecular biology, Cell biology, Enzyme Activation, Death-inducing signaling complex, biology.protein, Caspase 10, Dimerization
Abstract

Caspase 8 is an initiator caspase that is activated by death receptors to initiate the extrinsic pathway of apoptosis. Caspase 8 activation involves dimerization and subsequent interdomain autoprocessing of caspase 8 zymogens, and recently published work has established that elimination of the autoprocessing site of caspase 8 abrogates its pro-apoptotic function while leaving its proliferative function intact. The observation that the developmental abnormalities of caspase 8-deficient mice are shared by mice lacking the dimerization adapter FADD (Fas-associated death domain) or the caspase paralogue FLIPL [FLICE (FADD-like interleukin 1β-converting enzyme)-inhibitory protein, long form] has led to the hypothesis that FADD-dependent formation of heterodimers between caspase 8 and FLIPL could mediate the developmental role of caspase 8. In the present study, using an inducible dimerization system we demonstrate that cleavage of the catalytic domain of caspase 8 is crucial for its activity in the context of activation by homodimerization. However, we find that use of FLIPL as a partner for caspase 8 in dimerization-induced activation rescues the requirement for intersubunit linker proteolysis in both protomers. Moreover, before processing, caspase 8 in complex with FLIPL does not generate a fully active enzyme, but an attenuated species able to process only selected natural substrates. Based on these results we propose a mechanism of caspase 8 activation by dimerization in the presence of FLIPL, as well as a mechanism of caspase 8 functional divergence in apoptotic and non-apoptotic pathways.

Published
2011

145. PARTICULAR ASPECTS OF IMPACTED MAXILLARY CANINE IN CHILDREN – A NARRATIVE REVIEW

Author

Bianca-Andreea Onofrei, Carmen Savin, Cristina Popa, Ana Maria Șciucă, Mădălina Mihali, Ștefan Gherasimescu, Vasilica Toma, and Victor-Vlad Costan

Subjects
canine impaction, maxillary, children., Dentistry, RK1-715
Abstract

Canine impactions are frequently encountered in the pediatric population. Impacted canines may pose a functional and esthetic problem for patients and can affect the neighboring teeth (incisors and premolars). Early detection and management of such pathology may help the pediatric dentist and orthodontist to prevent many unwanted local and regional complications. Various surgical and orthodontic techniques may be used to recover impacted maxillary canines. The decision to surgically correct these impacted teeth is usually made by the orthodontist. The treatment of impacted teeth requires a multidisciplinary team comprising orthodontist, pediatric dentist, dento-alveolar surgeon, and sometimes a periodontist.

Published
2022

146. Activation and Specificity of Human Caspase-10

Author

Christian M. Zmasek, Stefan J. Riedl, Marcin Drag, Scott J. Snipas, Cristina Pop, Katherine Wachmann, Peter D. Mace, Bram J. van Raam, Guy S. Salvesen, and Robert Schwarzenbacher

Subjects
Protease, biology, medicine.medical_treatment, Mutant, Wild type, Cleavage (embryo), Biochemistry, Article, Substrate Specificity, Enzyme Activation, Enzyme activator, Apoptosis, Endopeptidases, biology.protein, medicine, Humans, Caspase 10, Dimerization, Caspase, BH3 Interacting Domain Death Agonist Protein
Abstract

Two apical caspases, caspase-8 and-10, are involved in the extrinsic death receptor pathway in humans but it is mainly caspase-8 in its apoptotic and non-apoptotic functions that has been an intense research focus. In this study we concentrate on caspase-10, its mechanism of activation and the role of the inter-subunit cleavage. Our data obtained through in vitro dimerization assays strongly suggest that caspase-10 follows the proximity–induced dimerization model for apical caspases. Furthermore, we compare the specificity and activity of the wildtype protease with a mutant incapable of autoprocessing, by using positional scanning substrate analysis and cleavage of natural protein substrates. These experiments reveal a striking difference between the wildtype and the mutant, leading us to hypothesize that the single chain enzyme has restricted activity on most proteins, but high activity on the pro-apoptotic protein Bid, potentially supporting a pro-death role for both cleaved and uncleaved caspase-10.

Published
2010

147. CLINICAL AND PSYCHOLOGICAL IMPACT OF SARS-COV-2 INFECTION IN BURNING-MOUTH SYNDROME PATIENTS: A COMPARATIVE STUDY

Author

Cosmin Dugan, Bogdan Ovidiu Popescu, Ioanina Părlătescu, Monica Dobre, Elena Milanesi, and Cristina Popa

Subjects
burning mouth syndrome, coronavirus infection, oral burning sensation, Dentistry, RK1-715
Abstract

Burning mouth syndrome (BMS) is a chronic disease characterized by the presence of persistent oral mucosa pain, mainly burning sensation without any detectable clinical cause or modified general investigations. Coronavirus infections, in some patients, caused sensations of oral burning, of a neuropathic nature, which mimicked the symptoms of BMS. In addition, the psychiatric manifestations associated with the COVID-19 pandemic have exacerbated the symptoms of patients already diagnosed with burning mouth syndrome. Based on these observations, we conducted a longitudinal study to assess the changes in depressive and anxiety symptoms in BMS patients during the pandemics. We recruited two groups of age and gender-matched BMS patients. The first group included patients with BMS diagnosed with coronavirus infection and the second one without coronavirus infection. The study concluded that in patients with coronavirus infection there was an intensification of anxiety-depressive symptoms more pronounced in the first 6 months after infection (duration being associated with the infection severity and long-COVID symptoms), followed by a recurrence or even decrease in symptoms compared to the initial examination. Oral symptomatology had a similar evolution, the intensity being determined by the severity of the COVID-19 infection episode and by the prolonged use of antivirals. The lack of a larger number of studies and patients with BMS and COVID-19 infection limited the possibility of comparative analyses.

Published
2022

148. A constitutively active and uninhibitable caspase-3 zymogen efficiently induces apoptosis

Author

Jad Walters, Fiona L. Scott, Cristina Pop, Paul Swartz, Guy S. Salvesen, Carla Mattos, A. Clay Clark, and Marcin Drag

Subjects
Models, Molecular, PARP, poly(ADP-ribose) polymerase, Protein Conformation, Dimer, Ac-DEVD-AFC, acetyl-Asp-Glu-Val-Asp-7-amino-4-trifluoromethylcoumarin, Apoptosis, Crystallography, X-Ray, Biochemistry, D3A,V266E, procaspase-3(D9A,D28A,D175A,V266E), Ac-DEVD-CMK, acetyl-Asp-Glu-Val-Asp-chloromethyl ketone, chemistry.chemical_compound, 0302 clinical medicine, conformational switch, D3A, procaspase-3(D9A,D28A,D175A), 0303 health sciences, Enzyme Precursors, Chemistry, Caspase 3, XIAP, Cell biology, HEK-293A cell, human embryonic kidney-293A cell, 030220 oncology & carcinogenesis, V266E, procaspase-3(V266E), XIAP, X-linked inhibitor of apoptosis, cancer therapy, Research Article, Programmed cell death, co-operative dimer interface, Blotting, Western, X-Linked Inhibitor of Apoptosis Protein, Inhibitor of apoptosis, Cleavage (embryo), WT, wild-type procaspase-3, Transfection, Cell Line, 03 medical and health sciences, Structure-Activity Relationship, Zymogen, Humans, Molecular Biology, 030304 developmental biology, Z-VAD-FMK, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, Binding Sites, Cell Biology, Molecular biology, procaspase activation, Protein Structure, Tertiary, IL, intersubunit linker, Enzyme Activation, bEVD-AOMK, biotinylhexanoyl-Asp-Glu-Val-acyloxymethane, Amino Acid Substitution, Mutation, Protein Multimerization
Abstract

The caspase-3 zymogen has essentially zero activity until it is cleaved by initiator caspases during apoptosis. However, a mutation of V266E in the dimer interface activates the protease in the absence of chain cleavage. We show that low concentrations of the pseudo-activated procaspase-3 kill mammalian cells rapidly and, importantly, this protein is not cleaved nor is it inhibited efficiently by the endogenous regulator XIAP (X-linked inhibitor of apoptosis). The 1.63 Å (1 Å = 0.1 nm) structure of the variant demonstrates that the mutation is accommodated at the dimer interface to generate an enzyme with substantially the same activity and specificity as wild-type caspase-3. Structural modelling predicts that the interface mutation prevents the intersubunit linker from binding in the dimer interface, allowing the active sites to form in the procaspase in the absence of cleavage. The direct activation of procaspase-3 through a conformational switch rather than by chain cleavage may lead to novel therapeutic strategies for inducing cell death.

Published
2009

149. Structural and kinetic determinants of protease substrates

Author

Cristina Pop, Stefan J. Riedl, Alexey Eroshkin, John C. Timmer, Guy S. Salvesen, Scott J. Snipas, Wenhong Zhu, and Tim Regan

Subjects
Proteomics, Protein Folding, Proteases, Protein Conformation, medicine.medical_treatment, Molecular Conformation, Biology, medicine.disease_cause, Biochemistry, Catalysis, Protein Structure, Secondary, Article, Substrate Specificity, Protein structure, Structural Biology, Cleave, Escherichia coli, medicine, Molecular Biology, Protease, Caspase 3, Protein Structure, Tertiary, Kinetics, Mutation, Proteome, Protein folding, Peptide Hydrolases, Signal Transduction
Abstract

Two fundamental questions with regard to proteolytic networks and pathways concern the structural repertoire and kinetic threshold that distinguish legitimate signaling substrates. We used N-terminal proteomics to address these issues by identifying cleavage sites within the Escherichia coli proteome that are driven by the apoptotic signaling protease caspase-3 and the bacterial protease glutamyl endopeptidase (GluC). Defying the dogma that proteases cleave primarily in natively unstructured loops, we found that both caspase-3 and GluC cleave in alpha-helices nearly as frequently as in extended loops. Notably, biochemical and kinetic characterization revealed that E. coli caspase-3 substrates are greatly inferior to natural substrates, suggesting protease and substrate coevolution. Engineering an E. coli substrate to match natural catalytic rates defined a kinetic threshold that depicts a signaling event. This unique combination of proteomics, biochemistry, kinetics and substrate engineering reveals new insights into the structure-function relationship of protease targets and their validation from large-scale approaches.

Published
2009

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