Author: "Kong, Y." / Topic: humans - Searchworks@Jio Institute Digital Library Search Results

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1. A Glycemia Risk Index (GRI) of Hypoglycemia and Hyperglycemia for Continuous Glucose Monitoring Validated by Clinician Ratings

Author: Klonoff, David C, Wang, Jing, Rodbard, David, Kohn, Michael A, Li, Chengdong, Liepmann, Dorian, Kerr, David, Ahn, David, Peters, Anne L, Umpierrez, Guillermo E, Seley, Jane Jeffrie, Xu, Nicole Y, Nguyen, Kevin T, Simonson, Gregg, Agus, Michael SD, Al-Sofiani, Mohammed E, Armaiz-Pena, Gustavo, Bailey, Timothy S, Basu, Ananda, Battelino, Tadej, Bekele, Sewagegn Yeshiwas, Benhamou, Pierre-Yves, Bequette, B Wayne, Blevins, Thomas, Breton, Marc D, Castle, Jessica R, Chase, James Geoffrey, Chen, Kong Y, Choudhary, Pratik, Clements, Mark A, Close, Kelly L, Cook, Curtiss B, Danne, Thomas, Doyle, Francis J, Drincic, Angela, Dungan, Kathleen M, Edelman, Steven V, Ejskjaer, Niels, Espinoza, Juan C, Fleming, G Alexander, Forlenza, Gregory P, Freckmann, Guido, Galindo, Rodolfo J, Gomez, Ana Maria, Gutow, Hanna A, Heinemann, Lutz, Hirsch, Irl B, Hoang, Thanh D, Hovorka, Roman, Jendle, Johan H, Ji, Linong, Joshi, Shashank R, Joubert, Michael, Koliwad, Suneil K, Lal, Rayhan A, Lansang, M Cecilia, Lee, Wei-An, Leelarathna, Lalantha, Leiter, Lawrence A, Lind, Marcus, Litchman, Michelle L, Mader, Julia K, Mahoney, Katherine M, Mankovsky, Boris, Masharani, Umesh, Mathioudakis, Nestoras N, Mayorov, Alexander, Messler, Jordan, Miller, Joshua D, Mohan, Viswanathan, Nichols, James H, Nørgaard, Kirsten, O’Neal, David N, Pasquel, Francisco J, Philis-Tsimikas, Athena, Pieber, Thomas, Phillip, Moshe, Polonsky, William H, Pop-Busui, Rodica, Rayman, Gerry, Rhee, Eun-Jung, Russell, Steven J, Shah, Viral N, Sherr, Jennifer L, Sode, Koji, Spanakis, Elias K, Wake, Deborah J, Waki, Kayo, Wallia, Amisha, Weinberg, Melissa E, Wolpert, Howard, Wright, Eugene E, Zilbermint, Mihail, and Kovatchev, Boris
Subjects: Biomedical and Clinical Sciences, Nutrition and Dietetics, Diabetes, Adult, Humans, Blood Glucose, Blood Glucose Self-Monitoring, Hypoglycemia, Hyperglycemia, Glucose, ambulatory glucose profile, composite metric, continuous glucose monitor, diabetes, glycemia risk index, hyperglycemia, hypoglycemia, time in range, Nutrition and dietetics
Abstract: BackgroundA composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data.MethodsWe assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation.ResultsThe analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals.ConclusionThe GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.
Published: 2023

2. Digital Diabetes Congress 2017.

Author: Klonoff, David C, Kerr, David, Wong, Jenise C, Pavlovic, Yarmela, Koliwad, Suneil, Hu, Julia, Salber, Patricia, Aguilera, Adrian, Long, William, Hamilton, Giles, Chen, Kong Y, and Adi, Saleh
Subjects: Humans, Diabetes Mellitus, Telemedicine, Mobile Applications, Self-Management, apps, cybersecurity, data, digital diabetes, privacy, Clinical Research, Clinical Trials and Supportive Activities, Diabetes, Prevention, Pediatric, Behavioral and Social Science, Metabolic and endocrine, Good Health and Well Being, Nutrition and Dietetics
Abstract: The purpose of developing mobile applications for diabetes is generally to: (1) provide enhanced access to timely information for patients, health care professionals, and researchers; (2) facilitate remote monitoring and diagnosis of patients, often based on information delivered by wearable devices; (3) provide decision support to assist patients in selecting treatment; or (4) deliver timely recommendations for treatment to increase adherence to prescribed therapy. There is a perception that mobile applications can provide meaningful clinical benefits, however, there is only sparse convincing evidence to support this belief at the present time. Compounding this problem is the short life span of digital software, such that if a traditional type of randomized controlled trial is conducted on a product, by the time the study has been designed, approved by an IRB, conducted, and analyzed, the product might have significantly changed to a next generation system. Because of great interest in establishing what are the potential benefits, metrics of success, and appropriate components of mobile applications for diabetes, Diabetes Technology Society and William Sansum Diabetes Center launched the Digital Diabetes Congress, March 7-8, 2017, in San Francisco. This report contains summaries of the meeting's 12 sessions. Each summary was written by the session's moderator who helped develop the session prior to the event and keep it on track during the event. This meeting report presents a summary of how 57 panelists, speakers, and moderators, who are leaders in digital health, see the current and future landscape of digital health tools applied to diabetes.
Published: 2017

3. MiTF links Erk1/2 kinase and p21CIP1/WAF1activation after UVC radiation in normal human melanocytes and melanoma cells

Author: Liu, F, Singh, A, Yang, Z, Garcia, A, Kong, Y, and Meyskens, FL
Subjects: Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p21, Humans, Melanocytes, Melanoma, Microphthalmia-Associated Transcription Factor, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Phosphorylation, Proteasome Endopeptidase Complex, Serine, Ultraviolet Rays
Abstract: As a survival factor for melanocytes lineage cells, MiTF plays multiple roles in development and melanomagenesis. What role MiTF plays in the DNA damage response is currently unknown. In this report we observed that MiTF was phosphorylated at serine 73 after UVC radiation, which was followed by proteasome-mediated degradation. Unlike after c-Kit stimulation, inhibiting p90RSK-1 did not abolish the band shift of MiTF protein, nor did it abolish the UVC-mediated MiTF degradation, suggesting that phosphorylation on serine 73 by Erk1/2 is a key event after UVC. Furthermore, the MiTF-S73A mutant (Serine 73 changed to Alanine via site-directed mutagenesis) was unable to degrade and was continuously expressed after UVC exposure. Compared to A375 melanoma cells expressing wild-type MiTF (MiTF-WT), cells expressing MiTF-S73A mutant showed less p21WAF1/CIP1accumulation and a delayed p21WAF1/CIP1recovery after UVC. Consequently, cells expressing MiTF-WT showed a temporary G1 arrest after UVC, but cells expressing MiTF-S73A mutant or lack of MiTF expression did not. Finally, cell lines with high levels of MiTF expression showed higher resistance to UVC-induced cell death than those with low-level MiTF. These data suggest that MiTF mediates a survival signal linking Erk1/2 activation and p21WAF1/CIP1regulation via phosphorylation on serine 73, which facilitates cell cycle arrest. In addition, our data also showed that exposure to different wavelengths of UV light elicited different signal pathways involving MiTF. © 2010 Liu et al; licensee BioMed Central Ltd.
Published: 2010

4. Effects of interrupting daily sedentary behavior on children's glucose metabolism: A 6‐day randomized controlled trial

Author: Miranda M. Broadney, Britni R. Belcher, Nejla Ghane, Risha Sheni, Michael J. Jayson, Robert W. Trenschel, Shavonne M. Collins, Robert J. Brychta, Elisabeth K. Davis, Sheila M. Brady, Shanna B. Yang, Amber B. Courville, Kevin P. Smith, Douglas R. Rosing, Kong Y. Chen, and Jack A. Yanovski
Subjects: Blood Glucose, Cross-Over Studies, Adolescent, C-Peptide, Endocrinology, Diabetes and Metabolism, Postprandial Period, Article, Glucose, Pediatrics, Perinatology and Child Health, Internal Medicine, Humans, Insulin, Sedentary Behavior, Child, Exercise
Abstract: BACKGROUND: Metabolic disease risk in youth is influenced by sedentary behaviors. Acute in-lab studies show that, during a single day, interrupting a sedentary period with short bouts of physical activity improves glucometabolic outcomes. OBJECTIVE: To determine if acutely improved glucose metabolism persists after multi-day interruptions of sitting with walking brief bouts. We hypothesized that children who underwent interrupting sitting on multiple days would demonstrate lower insulin area under the curve during an oral glucose tolerance test compared to uninterrupted sitting. METHODS: Healthy, normoglycemic children (N=109) ages 7-11 years were randomized to one of two conditions: Control (3h of daily Uninterrupted Sitting) or Interrupted Sitting (3-min of moderate-intensity walking every 30min for 3h daily); with dietary intake controlled through provision of foodstuffs for the entire experiment. Participants attended six consecutive daily visits at a research ambulatory unit. The primary outcome was insulin area under the curve during the oral glucose tolerance test on day 6 during interrupted or uninterrupted sitting; secondary outcomes included glucose and c-peptide area under the curve, energy intake at a buffet meal on day 6, and free-living activity. RESULTS: Among 93 children (42 uninterrupted sitting, 51 interrupted sitting), daily interrupted sitting resulted in 21% lower insulin (β=0.102 CI:0.032–0.172, p=.005) and a 10% lower C-peptide (β=0.043, CI:0.001-0.084, p=0.045) area under the curve. Matsuda and Glucose Effectiveness Indices were also improved (p’s
Published: 2022
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5. Validation and utility of ARDS subphenotypes identified by machine-learning models using clinical data: an observational, multicohort, retrospective analysis

Author: Maddali, Manoj V, Churpek, Matthew, Pham, Tai, Rezoagli, Emanuele, Zhuo, Hanjing, Zhao, Wendi, June, He, Delucchi, Kevin L, Wang, Chunxue, Wickersham, Nancy, Mcneil, J Brennan, Jauregui, Alejandra, Serena, Ke, Vessel, Kathryn, Gomez, Antonio, Hendrickson, Carolyn M, Kangelaris, Kirsten N, Sarma, Aartik, Leligdowicz, Aleksandra, Liu, Kathleen D, Matthay, Michael A, Ware, Lorraine B, Laffey, John G, Bellani, Giacomo, Calfee, Carolyn S, Sinha, Pratik, Rios, Fernando, Van Haren, Frank, Sottiaux, T, Lora, Fredy S, Azevedo, Luciano C, Depuydt, P, Fan, Eddy, Bugedo, Guillermo, Qiu, Haibo, Gonzalez, Marcos, Silesky, Juan, Cerny, Vladimir, Nielsen, Jonas, Jibaja, Manuel, Pham, Tài, Wrigge, Hermann, Matamis, Dimitrios, Ranero, Jorge Luis, Hashemian, S. M, Amin, Pravin, Clarkson, Kevin, Kurahashi, Kiyoyasu, Villagomez, Asisclo, Zeggwagh, Amine Ali, Heunks, Leo M, Laake, Jon Henrik, Palo, Jose Emmanuel, do Vale Fernandes, Antero, Sandesc, Dorel, Arabi, Yaasen, Bumbasierevic, Vesna, Nin, Nicolas, Lorente, Jose A, Larsson, Anders, Piquilloud, Lise, Abroug, Fekri, Mcauley, Daniel F, Mcnamee, Lia, Hurtado, Javier, Bajwa, Ed, Démpaire, Gabriel, Francois, Guy M, Sula, Hektor, Nunci, Lordian, Cani, Alma, Zazu, Alan, Dellera, Christian, Insaurralde, Carolina S, Alejandro, Risso V, Daldin, Julio, Vinzio, Mauricio, Fernandez, Ruben O, Cardonnet, Luis P, Bettini, Lisandro R, Bisso, Mariano Carboni, Osman, Emilio M, Setten, Mariano G, Lovazzano, Pablo, Alvarez, Javier, Villar, Veronica, Milstein, Cesar, Pozo, Norberto C, Grubissich, Nicolas, Plotnikow, Gustavo A, Vasquez, Daniela N, Ilutovich, Santiago, Tiribelli, Norberto, Chena, Ariel, Pellegrini, Carlos A, Saenz, María G, Estenssoro, Elisa, Brizuela, Matias, Gianinetto, Hernan, Gomez, Pablo E, Cerrato, Valeria I, Bezzi, Marco G, Borello, Silvina A, Loiacono, Flavia A, Fernandez, Adriana M, Knowles, Serena, Reynolds, Claire, Inskip, Deborah M, Miller, Jennene J, Kong, Jing, Whitehead, Christina, Bihari, Shailesh, Seven, Aylin, Krstevski, Amanda, Rodgers, Helen J, Millar, Rebecca T, Mckenna, Toni E, Bailey, Irene M, Hanlon, Gabrielle C, Aneman, Anders, Lynch, Joan M, Azad, Raman, Neal, John, Woods, Paul W, Roberts, Brigit L, Kol, Mark R, Wong, Helen S, Riss, Katharina C, Staudinger, Thomas, Wittebole, Xavier, Berghe, Caroline, Bulpa, Pierre A, Dive, Alain M, Verstraete, Rik, Lebbinck, Herve, Depuydt, Pieter, Vermassen, Joris, Meersseman, Philippe, Ceunen, Helga, Rosa, Jonas I, Beraldo, Daniel O, Piras, Claudio, Ampinelli, Adenilton M R, Nassar Jr, Antonio P, Mataloun, Sergio, Moock, Marcelo, Thompson, Marlus M, Gonçalves, Claudio H, Antônio, Ana Carolina P, Ascoli, Aline, Biondi, Rodrigo S, Fontenele, Danielle C, Nobrega, Danielle, Sales, Vanessa M, Shindhe, Suresh, Ismail, Dk Maizatul Aiman B Pg Hj, Laffey, John, Beloncle, Francois, Davies, Kyle G, Cirone, Rob, Manoharan, Venika, Ismail, Mehvish, Goligher, Ewan C, Jassal, Mandeep, Nishikawa, Erin, Javeed, Areej, Curley, Gerard, Rittayamai, Nuttapol, Parotto, Matteo, Ferguson, Niall D, Mehta, Sangeeta, Knoll, Jenny, Pronovost, Antoine, Canestrini, Sergio, Bruhn, Alejandro R, Garcia, Patricio H, Aliaga, Felipe A, Farías, Pamela A, Yumha, Jacob S, Ortiz, Claudia A, Salas, Javier E, Saez, Alejandro A, Vega, Luis D, Labarca, Eduardo F, Martinez, Felipe T, Carreño, Nicolás G, Lora, Pilar, Liu, Haitao, Liu, Ling, Tang, Rui, Luo, Xiaoming, Youzhong, An, Zhao, Huiying, Gao, Yan, Zhai, Zhe, Zheng L, Ye, Wang, Wei, Wenwen, Li, Qingdong, Li, Zheng, Ruiqiang, Wenkui, Yu, Shen, Juanhong, Xinyu, Li, Tao, Yu, Weihua, Lu, Ya Q, Wu, Huang, Xiao B, Zhenyang, He, Yuanhua, Lu, Han, Hui, Zhang, Fan, Sun, Renhua, Wang, Hua X, Qin, Shu H, Zhu, Bao H, Zhao, Jun, Liu, Jian, Bin, Li, Liu, Jing L, Zhou, Fa C, Qiong J, Li, Zhang, Xing Y, Li-Xin, Zhou, Xin-Hua, Qiang, Jiang, Liangyan, Gao, Yuan N, Zhao, Xian Y, Yuan Y, Li, Xiao L, Li, Wang, Chunting, Yao, Qingchun, Rongguo, Yu, Chen, Kai, Shao, Huanzhang, Qin, Bingyu, Huang, Qing Q, Zhu, Wei H, Hang, Ai Y, Hua, Ma X, Yimin, Li, Yonghao, Xu, Yu D, Di, Ling, Long L, Qin, Tie H, Wang, Shou H, Qin, Junping, Han, Yi, Zhou, Suming, Vargas, Monica P, Silesky Jimenez, Juan I, González Rojas, Manuel A, Solis-Quesada, Jaime E, Ramirez-Alfaro, Christian M, Máca, Jan, Sklienka, Peter, Gjedsted, Jakob, Christiansen, Aage, Villamagua, Boris G, Llano, Miguel, Burtin, Philippe, Buzancais, Gautier, Beuret, Pascal, Pelletier, Nicolas, Mortaza, Satar, Mercat, Alain, Chelly, Jonathan, Jochmans, Sébastien, Terzi, Nicolas, Daubin, Cédric, Carteaux, Guillaume, de Prost, Nicolas, Chiche, Jean-Daniel, Daviaud, Fabrice, Fartoukh, Muriel, Barberet, Guillaume, Biehler, Jerome, Dellamonica, Jean, Doyen, Denis, Arnal, Jean-Michel, Briquet, Anais, Hraiech, Sami, Papazian, Laurent, Follin, Arnaud, Roux, Damien, Messika, Jonathan, Kalaitzis, Evangelos, Dangers, Laurence, Combes, Alain, Siu-Ming, Au, Béduneau, Gaetan, Carpentier, Dorothée, Zogheib, Elie H, Dupont, Herve, Ricome, Sylvie, Santoli, Francesco L, Besset, Sebastien L, Michel, Philippe, Gelée, Bruno, Danin, Pierre-Eric, Goubaux, Bernard, Crova, Philippe J, Phan, Nga T, Berkelmans, Frantz, Badie, Julio C, Tapponnier, Romain, Gally, Josette, Khebbeb, Samy, Herbrecht, Jean-Etienne, Schneider, Francis, Declercq, Pierre-Louis M, Rigaud, Jean-Philippe, Duranteau, Jacques, Harrois, Anatole, Chabanne, Russell, Marin, Julien, Bigot, Charlene, Thibault, Sandrine, Ghazi, Mohammed, Boukhazna, Messabi, Ould Zein, Salem, Richecoeur, Jack R, Combaux, Daniele M, Grelon, Fabien, Le Moal, Charlene, Sauvadet, Elise P, Robine, Adrien, Lemiale, Virginie, Reuter, Danielle, Dres, Martin, Demoule, Alexandre, Goldgran-Toledano, Dany, Baboi, Loredana, Guérin, Claude, Lohner, Ralph, Kraßler, Jens, Schäfer, Susanne, Zacharowski, Kai D, Meybohm, Patrick, Reske, Andreas W, Simon, Philipp, Hopf, Hans-Bernd F, Schuetz, Michael, Baltus, Thomas, Papanikolaou, Metaxia N, Papavasilopoulou, Theonymfi G, Zacharas, Giannis A, Ourailogloy, Vasilis, Mouloudi, Eleni K, Massa, Eleni V, Nagy, Eva O, Stamou, Electra E, Kiourtzieva, Ellada V, Oikonomou, Marina A, Avila, Luis E, Cortez, Cesar A, Citalán, Johanna E, Jog, Sameer A, Sable, Safal D, Shah, Bhagyesh, Gurjar, Mohan, Baronia, Arvind K, Memon, Mohammedfaruk, Muthuchellappan, Radhakrishnan, Ramesh, Venkatapura J, Shenoy, Anitha, Unnikrishnan, Ramesh, Dixit, Subhal B, Rhayakar, Rachana V, Ramakrishnan, Nagarajan, Bhardwaj, Vallish K, Mahto, Heera L, Sagar, Sudha V, Palaniswamy, Vijayanand, Ganesan, Deeban, Mohammadreza Hashemian, Seyed, Jamaati, Hamidreza, Heidari, Farshad, Meaney, Edel A, Nichol, Alistair, Knapman, Karl M, O'Croinin, Donall, Dunne, Eimhin S, Breen, Dorothy M, Clarkson, Kevin P, Jaafar, Rola F, Dwyer, Rory, Amir, Fahd, Ajetunmobi, Olaitan O, O'Muircheartaigh, Aogan C, Black, Colin S, Treanor, Nuala, Collins, Daniel V, Altaf, Wahid, Zani, Gianluca, Fusari, Maurizio, Spadaro, Savino, Volta, Carlo A, Graziani, Romano, Brunettini, Barbara, Palmese, Salvatore, Formenti, Paolo, Umbrello, Michele, Lombardo, Andrea, Pecci, Elisabetta, Botteri, Marco, Savioli, Monica, Protti, Alessandro, Mattei, Alessia, Schiavoni, Lorenzo, Tinnirello, Andrea, Todeschini, Manuel, Giarratano, Antonino, Cortegiani, Andrea, Sher, Sara, Rossi, Anna, Antonelli, Massimo M, Montini, Luca M, Casalena, Paolo, Scafetti, Sergio, Panarello, Giovanna, Occhipinti, Giovanna, Patroniti, Nicolò, Pozzi, Matteo, Biscione, Roberto R, Poli, Michela M, Raimondi, Ferdinando, Albiero, Daniela, Crapelli, Giulia, Beck, Eduardo, Pota, Vincenzo, Schiavone, Vincenzo, Molin, Alexandre, Tarantino, Fabio, Monti, Giacomo, Frati, Elena, Mirabella, Lucia, Cinnella, Gilda, Fossali, Tommaso, Colombo, Riccardo, Terragni, Pierpaolo, Pattarino, Ilaria, Mojoli, Francesco, Braschi, Antonio, Borotto, Erika E, Cracchiolo, Andrea N, Palma, Daniela M, Raponi, Francesco, Foti, Giuseppe, Vascotto, Ettore R, Coppadoro, Andrea, Brazzi, Luca, Floris, Leda, Iotti, Giorgio A, Venti, Aaron, Yamaguchi, Osamu, Takagi, Shunsuke, Maeyama, Hiroki N, Watanabe, Eizo, Yamaji, Yoshihiro, Shimizu, Kazuyoshi, Shiozaki, Kyoko, Futami, Satoru, Ryosuke, Sekine, Saito, Koji, Kameyama, Yoshinobu, Ueno, Keiko, Izawa, Masayo, Okuda, Nao, Suzuki, Hiroyuki, Harasawa, Tomofumi, Nasu, Michitaka, Takada, Tadaaki, Ito, Fumihito, Nunomiya, Shin, Koyama, Kansuke, Abe, Toshikazu, Andoh, Kohkichi, Kusumoto, Kohei, Hirata, Akira, Takaba, Akihiro, Kimura, Hiroyasu, Matsumoto, Shuhei, Higashijima, Ushio, Honda, Hiroyuki, Aoki, Nobumasa, Imai, Hiroshi, Ogino, Yasuaki, Mizuguchi, Ichiko, Ichikado, Kazuya, Nitta, Kenichi, Mochizuki, Katsunori, Hashida, Tomoaki, Tanaka, Hiroyuki, Nakamura, Tomoyuki, Niimi, Daisuke, Ueda, Takeshi, Kashiwa, Yozo, Uchiyama, Akinori, Sabelnikovs, Olegs, Oss, Peteris, Haddad, Youssef, Liew, Kong Y, Ñamendys-Silva, Silvio A, Jarquin-Badiola, Yves D, Sanchez-Hurtado, Luis A, Gomez-Flores, Saira S, Marin, Maria C, Villagomez, Asisclo J, Lemus, Jordana S, Fierro, Jonathan M, Cervantes, Mavy Ramirez, Mejia, Francisco Javier Flores, Gonzalez, Daniel R, Dector, Dulce M, Estrella, Claudia R, Sanchez-Medina, Jorge R, Ramirez-Gutierrez, Alvaro, George, Fernando G, Aguirre, Janet S, Buensuseso, Juan A, Poblano, Manuel, Dendane, Tarek, Balkhi, Hicham, Elkhayari, Mina, Samkaoui, Nacer, Ezzouine, Hanane, Benslama, Abdellatif, Amor, Mourad, Maazouzi, Wajdi, Cimic, Nedim, Beck, Oliver, Bruns, Monique M, Schouten, Jeroen A, Rinia, Myra, Raaijmakers, Monique, Van Wezel, Hellen M, Heines, Serge J, Buise, Marc P, Simonis, Fabienne D, Schultz, Marcus J, Goodson, Jennifer C, Rowne, Troy S B, Navarra, Leanlove, Hunt, Anna, Hutchison, Robyn A, Bailey, Mathew B, Newby, Lynette, Mcarthur, Colin, Kalkoff, Michael, Mcleod, Alex, Casement, Jonathan, Hacking, Danielle J, Andersen, Finn H, Dolva, Merete S, Laake, Jon H, Barratt-Due, Andreas, Noremark, Kim Andre L, Søreide, Eldar, Sjøbø, Brit Å, Guttormsen, Anne B, Yoshido, Hector H Leon, Aguilar, Ronald Zumaran, Oscanoa, Fredy A Montes, Alisasis, Alain U, Robles, Joanne B, Pasanting-Lim, Rossini Abbie B, Tan, Beatriz C, Andruszkiewicz, Pawel, Jakubowska, Karina, Cox, Cristina M, Alvarez, António M, Oliveira, Bruno S, Montanha, Gustavo M, Barros, Nelson C, Pereira, Carlos S, Messias, António M, Monteiro, Jorge M, Araujo, Ana M, Catorze, Nuno T, Marum, Susan M, Bouw, Maria J, Gomes, Rui M, Brito, Vania A, Castro, Silvia, Estilita, Joana M, Barros, Filipa M, Serra, Isabel M, Martinho, Aurelia M, Tomescu, Dana R, Marcu, Alexandra, Bedreag, Ovidiu H, Papurica, Marius, Corneci, Dan E, Negoita, Silvius Ioan, Grigoriev, Evgeny, Gritsan, Alexey I, Gazenkampf, Andrey A, Almekhlafi, Ghaleb, Albarrak, Mohamad M, Mustafa, Ghanem M, Maghrabi, Khalid A, Salahuddin, Nawal, Aisa, Tharwat M, Al Jabbary, Ahmed S, Tabhan, Edgardo, Arabi, Yaseen M, Trinidad, Olivia A, Al Dorzi, Hasan M, Tabhan, Edgardo E, Bolon, Stefan, Smith, Oliver, Mancebo, Jordi, Aguirre-Bermeo, Hernan, Lopez-Delgado, Juan C, Esteve, Francisco, Rialp, Gemma, Forteza, Catalina, De Haro, Candelaria, Artigas, Antonio, Albaiceta, Guillermo M, De Cima-Iglesias, Sara, Seoane-Quiroga, Leticia, Ceniceros-Barros, Alexandra, Ruiz-Aguilar, Antonio L, Claraco-Vega, Luis M, Soler, Juan Alfonso, Lorente, Maria del Carmen, Hermosa, Cecilia, Gordo, Federico, Prieto-González, Miryam, López-Messa, Juan B, Perez, Manuel P, Pere, Cesar P, Allue, Raquel Montoiro, Roche-Campo, Ferran, Ibañez-Santacruz, Marcos, Temprano, Susana, Pintado, Maria C, De Pablo, Raul, Gómez, Pilar Ricart Aroa, Ruiz, Silvia Rodriguez, Moles, Silvia Iglesias, Jurado, Mª Teresa, Arizmendi, Alfons, Piacentini, Enrique A, Franco, Nieves, Honrubia, Teresa, Perez Cheng, Meisy, Perez Losada, Elena, Blanco, Javier, Yuste, Luis J, Carbayo-Gorriz, Cecilia, Cazorla-Barranquero, Francisca G, Alonso, Javier G, Alda, Rosa S, Algaba, Ángela, Navarro, Gonzalo, Cereijo, Enrique, Diaz-Rodriguez, Esther, Marcos, Diego Pastor, Montero, Laura Alvarez, Para, Luis Herrera, Sanchez, Roberto Jimenez, Blasco Navalpotro, Miguel Angel, Abad, Ricardo Diaz, Montiel González, Raquel, Toribio, Dácil Parrilla, Castro, Alejandro G, Artiga, Maria Jose D, Penuelas, Oscar, Roser, Tomas P, Olga, Moreno F, Curto, Elena Gallego, Sánchez, Rocío Manzano, Imma, Vallverdu P, Elisabet, Garcia M, Claverias, Laura, Magret, Monica, Pellicer, Ana M, Rodriguez, Lucia L, Sánchez-Ballesteros, Jesús, González-Salamanca, Ángela, Jimenez, Antonio G, Huerta, Francisco P, Diaz, Juan Carlos J Sotillo, Lopez, Esther Bermejo, Moya, David D Llinares, Alfonso, Alec A Tallet, Eugenio Luis, Palazon Sanchez, Cesar, Palazon Sanchez, Rafael, Sánchez I, Virgilio, Corcoles G, Recio, Noelia N, Adamsson, Richard O, Rylander, Christian C, Holzgraefe, Bernhard, Broman, Lars M, Wessbergh, Joanna, Persson, Linnea, Schiöler, Fredrik, Kedelv, Hans, Tibblin, Anna 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Donnelly, Adrian, Frigyik, Aniko D, Careless, Jon P, May, Martin M, Stewart, Richard, Trinder, T John, Hagan, Samantha J, Wise, Matt P, Cole, Jade M, Macfie, Caroline C, Dowling, Anna T, Nuñez, Edgardo, Pittini, Gustavo, Rodriguez, Ruben, Imperio, María C, Santos, Cristina, França, Ana G., Ebeid, Alejandro, Deicas, Alberto, Serra, Carolina, Uppalapati, Aditya, Kamel, Ghassan, Banner-Goodspeed, Valerie M, Beitler, Jeremy R, Mukkera, Satyanarayana Reddy, Kulkarni, Shreedhar, Lee, Jarone, Mesar, Tomaz, Shinn Iii, John O, Gomaa, Dina, Tainter, Christopher, Cowley, R Adams, Yeatts, Dale J, Warren, Jessica, Lanspa, Michael J, Miller, Russel R, Grissom, Colin K, Brown, Samuel M, Bauer, Philippe R, Gosselin, Ryan J, Kitch, Barrett T, Cohen, Jason E, Beegle, Scott H, Gueret, Renaud M, Tulaimat, Aiman, Choudry, Shazia, Stigler, William, Batra, Hitesh, Huff, Nidhi G, Lamb, Keith D, Oetting, Trevor W, Mohr, Nicholas M, Judy, Claine, Saito, Shigeki, Kheir, Fayez M, Schlichting, Adam B, Delsing, 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C., Hermosa, C., Gordo, F., Prieto-Gonzalez, M., Lopez-Messa, J. B., Perez, M. P., Pere, C. P., Allue, R. M., Roche-Campo, F., Ibanez-Santacruz, M., Temprano, S., Pintado, M. C., De Pablo, R., Gomez, P. R. A., Ruiz, S. R., Moles, S. I., Jurado, M. T., Arizmendi, A., Piacentini, E. A., Franco, N., Honrubia, T., Perez Cheng, M., Perez Losada, E., Blanco, J., Yuste, L. J., Carbayo-Gorriz, C., Cazorla-Barranquero, F. G., Alonso, J. G., Alda, R. S., Algaba, A., Navarro, G., Cereijo, E., Diaz-Rodriguez, E., Marcos, D. P., Montero, L. A., Para, L. H., Sanchez, R. J., Blasco Navalpotro, M. A., Abad, R. D., Montiel Gonzalez, R., Toribio, D. P., Castro, A. G., Artiga, M. J. D., Penuelas, O., Roser, T. P., Olga, M. F., Curto, E. G., Sanchez, R. M., Imma, V. P., Elisabet, G. M., Claverias, L., Magret, M., Pellicer, A. M., Rodriguez, L. L., Sanchez-Ballesteros, J., Gonzalez-Salamanca, A., Jimenez, A. G., Huerta, F. P., Diaz, J. C. J. S., Lopez, E. B., Moya, D. D. L., Alfonso, A. A. 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T., Nunez, E., Pittini, G., Rodriguez, R., Imperio, M. C., Santos, C., Franca, A. G., Ebeid, A., Deicas, A., Serra, C., Uppalapati, A., Kamel, G., Banner-Goodspeed, V. M., Beitler, J. R., Mukkera, S. R., Kulkarni, S., Lee, J., Mesar, T., Shinn Iii, J. O., Gomaa, D., Tainter, C., Cowley, R. A., Yeatts, D. J., Warren, J., Lanspa, M. J., Miller, R. R., Grissom, C. K., Brown, S. M., Bauer, P. R., Gosselin, R. J., Kitch, B. T., Cohen, J. E., Beegle, S. H., Gueret, R. M., Tulaimat, A., Choudry, S., Stigler, W., Batra, H., Huff, N. G., Lamb, K. D., Oetting, T. W., Mohr, N. M., Judy, C., Saito, S., Kheir, F. M., Schlichting, A. B., Delsing, A., Elmasri, M., Crouch, D. R., Ismail, D., Blakeman, T. C., Dreyer, K. R., Baron, R. M., Grijalba, C. Q., Hou, P. C., Seethala, R., Aisiku, I., Henderson, G., Frendl, G., Hou, S. -K., Owens, R. L., Schomer, A., Bumbasirevic, V., Jovanovic, B., Surbatovic, M., Veljovic, M., UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (SLuc) Service de soins intensifs, UCL - (MGD) Services des soins intensifs, Maddali, Manoj V, Churpek, Matthew, Pham, Tai, Rezoagli, Emanuele, Zhuo, Hanjing, Zhao, Wendi, He, June, Delucchi, Kevin L, Wang, Chunxue, Wickersham, Nancy, McNeil, J Brennan, Jauregui, Alejandra, Ke, Serena, Vessel, Kathryn, Gomez, Antonio, Hendrickson, Carolyn M, Kangelaris, Kirsten N, Sarma, Aartik, Leligdowicz, Aleksandra, Liu, Kathleen D, Matthay, Michael A, Ware, Lorraine B, Laffey, John G, Bellani, Giacomo, Calfee, Carolyn S, Sinha, Pratik, Rios, Fernando, Van Haren, Frank, Sottiaux, T, Lora, Fredy S, Azevedo, Luciano C, Depuydt, P, Fan, Eddy, Bugedo, Guillermo, Qiu, Haibo, Gonzalez, Marco, Silesky, Juan, Cerny, Vladimir, Nielsen, Jona, Jibaja, Manuel, Pham, Tài, Wrigge, Hermann, Matamis, Dimitrio, Ranero, Jorge Lui, Hashemian, S. 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Cerrato, Valeria I, Bezzi, Marco G, Borello, Silvina A, Loiacono, Flavia A, Fernandez, Adriana M, Knowles, Serena, Reynolds, Claire, Inskip, Deborah M, Miller, Jennene J, Kong, Jing, Whitehead, Christina, Bihari, Shailesh, Seven, Aylin, Krstevski, Amanda, Rodgers, Helen J, Millar, Rebecca T, Mckenna, Toni E, Bailey, Irene M, Hanlon, Gabrielle C, Aneman, Ander, Lynch, Joan M, Azad, Raman, Neal, John, Woods, Paul W, Roberts, Brigit L, Kol, Mark R, Wong, Helen S, Riss, Katharina C, Staudinger, Thoma, Wittebole, Xavier, Berghe, Caroline, Bulpa, Pierre A, Dive, Alain M, Verstraete, Rik, Lebbinck, Herve, Depuydt, Pieter, Vermassen, Jori, Meersseman, Philippe, Ceunen, Helga, Rosa, Jonas I, Beraldo, Daniel O, Piras, Claudio, Ampinelli, Adenilton M R, Nassar Jr, Antonio P, Mataloun, Sergio, Moock, Marcelo, Thompson, Marlus M, Gonçalves, Claudio H, Antônio, Ana Carolina P, Ascoli, Aline, Biondi, Rodrigo S, Fontenele, Danielle C, Nobrega, Danielle, Sales, Vanessa M, Shindhe, Suresh, Ismail, Dk Maizatul Aiman B Pg Hj, Laffey, John, Beloncle, Francoi, Davies, Kyle G, Cirone, Rob, Manoharan, Venika, Ismail, Mehvish, Goligher, Ewan C, Jassal, Mandeep, Nishikawa, Erin, Javeed, Areej, Curley, Gerard, Rittayamai, Nuttapol, Parotto, Matteo, Ferguson, Niall D, Mehta, Sangeeta, Knoll, Jenny, Pronovost, Antoine, Canestrini, Sergio, Bruhn, Alejandro R, Garcia, Patricio H, Aliaga, Felipe A, Farías, Pamela A, Yumha, Jacob S, Ortiz, Claudia A, Salas, Javier E, Saez, Alejandro A, Vega, Luis D, Labarca, Eduardo F, Martinez, Felipe T, Carreño, Nicolás G, Lora, Pilar, Liu, Haitao, Liu, Ling, Tang, Rui, Luo, Xiaoming, An, Youzhong, Zhao, Huiying, Gao, Yan, Zhai, Zhe, Ye, Zheng L, Wang, Wei, Li, Wenwen, Li, Qingdong, Zheng, Ruiqiang, Yu, Wenkui, Shen, Juanhong, Li, Xinyu, Yu, Tao, Lu, Weihua, Wu, Ya Q, Huang, Xiao B, He, Zhenyang, Lu, Yuanhua, Han, Hui, Zhang, Fan, Sun, Renhua, Wang, Hua X, Qin, Shu H, Zhu, Bao H, Zhao, Jun, Liu, Jian, Li, Bin, Liu, Jing L, Zhou, Fa C, Li, Qiong J, Zhang, Xing 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S, Treanor, Nuala, Collins, Daniel V, Altaf, Wahid, Zani, Gianluca, Fusari, Maurizio, Spadaro, Savino, Volta, Carlo A, Graziani, Romano, Brunettini, Barbara, Palmese, Salvatore, Formenti, Paolo, Umbrello, Michele, Lombardo, Andrea, Pecci, Elisabetta, Botteri, Marco, Savioli, Monica, Protti, Alessandro, Mattei, Alessia, Schiavoni, Lorenzo, Tinnirello, Andrea, Todeschini, Manuel, Giarratano, Antonino, Cortegiani, Andrea, Sher, Sara, Rossi, Anna, Antonelli, Massimo M, Montini, Luca M, Casalena, Paolo, Scafetti, Sergio, Panarello, Giovanna, Occhipinti, Giovanna, Patroniti, Nicolò, Pozzi, Matteo, Biscione, Roberto R, Poli, Michela M, Raimondi, Ferdinando, Albiero, Daniela, Crapelli, Giulia, Beck, Eduardo, Pota, Vincenzo, Schiavone, Vincenzo, Molin, Alexandre, Tarantino, Fabio, Monti, Giacomo, Frati, Elena, Mirabella, Lucia, Cinnella, Gilda, Fossali, Tommaso, Colombo, Riccardo, Terragni, Pierpaolo, Pattarino, Ilaria, Mojoli, Francesco, Braschi, Antonio, Borotto, Erika E, Cracchiolo, Andrea N, Palma, Daniela M, Raponi, Francesco, Foti, Giuseppe, Vascotto, Ettore R, Coppadoro, Andrea, Brazzi, Luca, Floris, Leda, Iotti, Giorgio A, Venti, Aaron, Yamaguchi, Osamu, Takagi, Shunsuke, Maeyama, Hiroki N, Watanabe, Eizo, Yamaji, Yoshihiro, Shimizu, Kazuyoshi, Shiozaki, Kyoko, Futami, Satoru, Ryosuke, Sekine, Saito, Koji, Kameyama, Yoshinobu, Ueno, Keiko, Izawa, Masayo, Okuda, Nao, Suzuki, Hiroyuki, Harasawa, Tomofumi, Nasu, Michitaka, Takada, Tadaaki, Ito, Fumihito, Nunomiya, Shin, Koyama, Kansuke, Abe, Toshikazu, Andoh, Kohkichi, Kusumoto, Kohei, Hirata, Akira, Takaba, Akihiro, Kimura, Hiroyasu, Matsumoto, Shuhei, Higashijima, Ushio, Honda, Hiroyuki, Aoki, Nobumasa, Imai, Hiroshi, Ogino, Yasuaki, Mizuguchi, Ichiko, Ichikado, Kazuya, Nitta, Kenichi, Mochizuki, Katsunori, Hashida, Tomoaki, Tanaka, Hiroyuki, Nakamura, Tomoyuki, Niimi, Daisuke, Ueda, Takeshi, Kashiwa, Yozo, Uchiyama, Akinori, Sabelnikovs, Oleg, Oss, Peteri, Haddad, Youssef, Liew, Kong Y, Ñamendys-Silva, Silvio A, Jarquin-Badiola, Yves D, Sanchez-Hurtado, Luis A, Gomez-Flores, Saira S, Marin, Maria C, Villagomez, Asisclo J, Lemus, Jordana S, Fierro, Jonathan M, Cervantes, Mavy Ramirez, Mejia, Francisco Javier Flore, Gonzalez, Daniel R, Dector, Dulce M, Estrella, Claudia R, Sanchez-Medina, Jorge R, Ramirez-Gutierrez, Alvaro, George, Fernando G, Aguirre, Janet S, Buensuseso, Juan A, Poblano, Manuel, Dendane, Tarek, Balkhi, Hicham, Elkhayari, Mina, Samkaoui, Nacer, Ezzouine, Hanane, Benslama, Abdellatif, Amor, Mourad, Maazouzi, Wajdi, Cimic, Nedim, Beck, Oliver, Bruns, Monique M, Schouten, Jeroen A, Rinia, Myra, Raaijmakers, Monique, Van Wezel, Hellen M, Heines, Serge J, Buise, Marc P, Simonis, Fabienne D, Schultz, Marcus J, Goodson, Jennifer C, rowne, Troy S B, Navarra, Leanlove, Hunt, Anna, Hutchison, Robyn A, Bailey, Mathew B, Newby, Lynette, Mcarthur, Colin, Kalkoff, Michael, Mcleod, Alex, Casement, Jonathan, Hacking, Danielle J, Andersen, Finn H, Dolva, Merete S, Laake, Jon H, Barratt-Due, Andrea, Noremark, Kim Andre L, Søreide, Eldar, Sjøbø, Brit Å, Guttormsen, Anne B, Yoshido, Hector H Leon, Aguilar, Ronald Zumaran, Oscanoa, Fredy A Monte, Alisasis, Alain U, Robles, Joanne B, Pasanting-Lim, Rossini Abbie B, Tan, Beatriz C, Andruszkiewicz, Pawel, Jakubowska, Karina, Cox, Cristina M, Alvarez, António M, Oliveira, Bruno S, Montanha, Gustavo M, Barros, Nelson C, Pereira, Carlos S, Messias, António M, Monteiro, Jorge M, Araujo, Ana M, Catorze, Nuno T, Marum, Susan M, Bouw, Maria J, Gomes, Rui M, Brito, Vania A, Castro, Silvia, Estilita, Joana M, Barros, Filipa M, Serra, Isabel M, Martinho, Aurelia M, Tomescu, Dana R, Marcu, Alexandra, Bedreag, Ovidiu H, Papurica, Mariu, Corneci, Dan E, Negoita, Silvius Ioan, Grigoriev, Evgeny, Gritsan, Alexey I, Gazenkampf, Andrey A, Almekhlafi, Ghaleb, Albarrak, Mohamad M, Mustafa, Ghanem M, Maghrabi, Khalid A, Salahuddin, Nawal, Aisa, Tharwat M, Al Jabbary, Ahmed S, Tabhan, Edgardo, Arabi, Yaseen M, Trinidad, Olivia A, Al Dorzi, Hasan M, Tabhan, Edgardo E, Bolon, Stefan, Smith, Oliver, Mancebo, Jordi, Aguirre-Bermeo, Hernan, Lopez-Delgado, Juan C, Esteve, Francisco, Rialp, Gemma, Forteza, Catalina, De Haro, Candelaria, Artigas, Antonio, Albaiceta, Guillermo M, De Cima-Iglesias, Sara, Seoane-Quiroga, Leticia, Ceniceros-Barros, Alexandra, Ruiz-Aguilar, Antonio L, Claraco-Vega, Luis M, Soler, Juan Alfonso, Lorente, Maria del Carmen, Hermosa, Cecilia, Gordo, Federico, Prieto-González, Miryam, López-Messa, Juan B, Perez, Manuel P, Pere, Cesar P, Allue, Raquel Montoiro, Roche-Campo, Ferran, Ibañez-Santacruz, Marco, Temprano, Susana, Pintado, Maria C, De Pablo, Raul, Gómez, Pilar Ricart Aroa, Ruiz, Silvia Rodriguez, Moles, Silvia Iglesia, Jurado, Mª Teresa, Arizmendi, Alfon, Piacentini, Enrique A, Franco, Nieve, Honrubia, Teresa, Perez Cheng, Meisy, Perez Losada, Elena, Blanco, Javier, Yuste, Luis J, Carbayo-Gorriz, Cecilia, Cazorla-Barranquero, Francisca G, Alonso, Javier G, Alda, Rosa S, Algaba, Ángela, Navarro, Gonzalo, Cereijo, Enrique, Diaz-Rodriguez, Esther, Marcos, Diego Pastor, Montero, Laura Alvarez, Para, Luis Herrera, Sanchez, Roberto Jimenez, Blasco Navalpotro, Miguel Angel, Abad, Ricardo Diaz, Montiel González, Raquel, Toribio, Dácil Parrilla, Castro, Alejandro G, Artiga, Maria Jose D, Penuelas, Oscar, Roser, Tomas P, Olga, Moreno F, Curto, Elena Gallego, Sánchez, Rocío Manzano, Imma, Vallverdu P, Elisabet, Garcia M, Claverias, Laura, Magret, Monica, Pellicer, Ana M, Rodriguez, Lucia L, Sánchez-Ballesteros, Jesú, González-Salamanca, Ángela, Jimenez, Antonio G, Huerta, Francisco P, Diaz, Juan Carlos J Sotillo, Lopez, Esther Bermejo, Moya, David D Llinare, Alfonso, Alec A Tallet, Eugenio Luis, Palazon Sanchez, Cesar, Palazon Sanchez, Rafael, Sánchez I, Virgilio, Corcoles G, Recio, Noelia N, Adamsson, Richard O, Rylander, Christian C, Holzgraefe, Bernhard, Broman, Lars M, Wessbergh, Joanna, Persson, Linnea, Schiöler, Fredrik, Kedelv, Han, Tibblin, Anna Oscarsson, Appelberg, Henrik, Hedlund, Lar, Helleberg, Johan, Eriksson, Karin E, Glietsch, Rita, Larsson, Nikla, Nygren, Ingela, Nunes, Silvia L, Morin, Anna-Karin, Kander, Thoma, Adolfsson, Anne, Zender, Hervé O., Leemann-Refondini, Corinne, Elatrous, Souheil, Bouchoucha, Slaheddine, Chouchene, Imed, Ouanes, Islem, Ben Souissi, Asma, Kamoun, Salma, Demirkiran, Oktay, Aker, Mustafa, Erbabacan, Emre, Ceylan, Ilkay, Girgin, Nermin Kelebek, Ozcelik, Menekse, Ünal, Necmettin, Meco, Basak Ceyda, Akyol, Onat O, Derman, Suleyman S, Kennedy, Barry, Parhar, Ken, Srinivasa, Latha, McAuley, Danny, Steinberg, Jack, Hopkins, Phil, Mellis, Clare, Stansil, Frank, Kakar, Vivek, Hadfield, Dan, Brown, Christine, Vercueil, Andre, Bhowmick, Kaushik, Humphreys, Sally K, Ferguson, Andrew, Mckee, Raymond, Raj, Ashok S, Fawkes, Danielle A, Watt, Philip, Twohey, Linda, Thomas, Rajeev R Jha Matthew, Morton, Alex, Kadaba, Varsha, Smith, Mark J, Hormis, Anil P, Kannan, Santhana G, Namih, Miriam, Reschreiter, Henrik, Camsooksai, Julie, Kumar, Alek, Rugonfalvi, Szabolc, Nutt, Christopher, Oneill, Orla, Seasman, Colette, Dempsey, Ged, Scott, Christopher J, Ellis, Helen E, Mckechnie, Stuart, Hutton, Paula J, Di Tomasso, Nora N, Vitale, Michela N, Griffin, Ruth O, Dean, Michael N, Cranshaw, Julius H, Willett, Emma L, Ioannou, Nichola, Gillis, Sarah, Csabi, Peter, Macfadyen, Rosaleen, Dawson, Heidi, Preez, Pieter D, Williams, Alexandra J, Boyd, Owen, De Gordoa, Laura Ortiz-Ruiz, Bramall, Jon, Symmonds, Sophie, Chau, Simon K, Wenham, Tim, Szakmany, Tama, Toth-Tarsoly, Piroska, Mccalman, Katie H, Alexander, Peter, Stephenson, Lorraine, Collyer, Thoma, Chapman, Rhiannon, Cooper, Raphael, Allan, Russell M, Sim, Malcolm, Wrathall, David W, Irvine, Donald A, Zantua, Kim S, Adams, John C, Burtenshaw, Andrew J, Sellors, Gareth P, Welters, Ingeborg D, Williams, Karen E, Hessell, Robert J, Oldroyd, Matthew G, Battle, Ceri E, Pillai, Suresh, Kajtor, Istvan, Sivashanmugave, Mageswaran, Okane, Sinead C, Donnelly, Adrian, Frigyik, Aniko D, 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Ismail, Dina, Blakeman, Thomas C, Dreyer, Kyle R, Baron, Rebecca M, Grijalba, Carolina Quintana, Hou, Peter C, Seethala, Raghu, Aisiku, Imo, Henderson, Galen, Frendl, Gyorgy, Hou, Sen-Kuang, Owens, Robert L, Schomer, Ashley, Bumbasirevic, Vesna, Jovanovic, Bojan, Surbatovic, Maja, Veljovic, Milic, Intensive Care Medicine, ACS - Pulmonary hypertension & thrombosis, AII - Inflammatory diseases, ACS - Diabetes & metabolism, ACS - Microcirculation, Maddali, M, Churpek, M, Pham, T, Rezoagli, E, Zhuo, H, Zhao, W, He, J, Delucchi, K, Wang, C, Wickersham, N, Mcneil, J, Jauregui, A, Ke, S, Vessel, K, Gomez, A, Hendrickson, C, Kangelaris, K, Sarma, A, Leligdowicz, A, Liu, K, Matthay, M, Ware, L, Laffey, J, Bellani, G, Calfee, C, and Sinha, P
Subjects: Pulmonary and Respiratory Medicine, Clinical Sciences, Acute Lung Injury, Article, Machine Learning, Positive-Pressure Respiration, Rare Diseases, Clinical Research, Retrospective Studie, Settore MED/41 - ANESTESIOLOGIA, Humans, Lung, Acute Respiratory Distress Syndrome, Retrospective Studies, Respiratory Distress Syndrome, Other Medical and Health Sciences, LUNG SAFE Investigators and the ESICM Trials Group, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Phenotype, Good Health and Well Being, Area Under Curve, ARDS: Phenotype, Respiratory, Public Health and Health Services, ARDS, Human
Abstract: Item does not contain fulltext BACKGROUND: Two acute respiratory distress syndrome (ARDS) subphenotypes (hyperinflammatory and hypoinflammatory) with distinct clinical and biological features and differential treatment responses have been identified using latent class analysis (LCA) in seven individual cohorts. To facilitate bedside identification of subphenotypes, clinical classifier models using readily available clinical variables have been described in four randomised controlled trials. We aimed to assess the performance of these models in observational cohorts of ARDS. METHODS: In this observational, multicohort, retrospective study, we validated two machine-learning clinical classifier models for assigning ARDS subphenotypes in two observational cohorts of patients with ARDS: Early Assessment of Renal and Lung Injury (EARLI; n=335) and Validating Acute Lung Injury Markers for Diagnosis (VALID; n=452), with LCA-derived subphenotypes as the gold standard. The primary model comprised only vital signs and laboratory variables, and the secondary model comprised all predictors in the primary model, with the addition of ventilatory variables and demographics. Model performance was assessed by calculating the area under the receiver operating characteristic curve (AUC) and calibration plots, and assigning subphenotypes using a probability cutoff value of 0·5 to determine sensitivity, specificity, and accuracy of the assignments. We also assessed the performance of the primary model in EARLI using data automatically extracted from an electronic health record (EHR; EHR-derived EARLI cohort). In Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE; n=2813), a multinational, observational ARDS cohort, we applied a custom classifier model (with fewer variables than the primary model) to determine the prognostic value of the subphenotypes and tested their interaction with the positive end-expiratory pressure (PEEP) strategy, with 90-day mortality as the dependent variable. FINDINGS: The primary clinical classifier model had an area under receiver operating characteristic curve (AUC) of 0·92 (95% CI 0·90-0·95) in EARLI and 0·88 (0·84-0·91) in VALID. Performance of the primary model was similar when using exclusively EHR-derived predictors compared with manually curated predictors (AUC=0·88 [95% CI 0·81-0·94] vs 0·92 [0·88-0·97]). In LUNG SAFE, 90-day mortality was higher in patients assigned the hyperinflammatory subphenotype than in those with the hypoinflammatory phenotype (414 [57%] of 725 vs 694 [33%] of 2088; p
Published: 2022

6. Continuous Ketone Monitoring Consensus Report 2021

Author: Trisha Shang, Lori M. Laffel, Kevin T. Nguyen, Mark R. Prausnitz, Jane Jeffrie Seley, James H. Nichols, Ananda Basu, David C. Klonoff, Nestoras Mathioudakis, Jennifer L. Sherr, Kristin Castorino, Kong Y. Chen, Joshua D. Miller, Jennifer Y Zhang, Elias K. Spanakis, Priya Prahalad, David Kerr, Nicole Y. Xu, Guillermo E. Umpierrez, L. Kurt Midyett, Amisha Wallia, Francisco J. Pasquel, Suneil K. Koliwad, and Richard M. Bergenstal
Subjects: Adult, medicine.medical_specialty, Consensus, Diabetic ketoacidosis, Pediatric endocrinology, Endocrinology, Diabetes and Metabolism, Biomedical Engineering, Bioengineering, Diabetic Ketoacidosis, Epidemiology, Internal Medicine, medicine, Humans, Child, Monitoring, Physiologic, business.industry, Original Articles, Ketosis, Ketones, medicine.disease, Ketoacidosis, Clinical trial, Private practice, Family medicine, Ketonuria, business, Medical literature
Abstract: This article is the work product of the Continuous Ketone Monitoring Consensus Panel, which was organized by Diabetes Technology Society and met virtually on April 20, 2021. The panel consisted of 20 US-based experts in the use of diabetes technology, representing adult endocrinology, pediatric endocrinology, advanced practice nursing, diabetes care and education, clinical chemistry, and bioengineering. The panelists were from universities, hospitals, freestanding research institutes, government, and private practice. Panelists reviewed the medical literature pertaining to ten topics: (1) physiology of ketone production, (2) measurement of ketones, (3) performance of the first continuous ketone monitor (CKM) reported to be used in human trials, (4) demographics and epidemiology of diabetic ketoacidosis (DKA), (5) atypical hyperketonemia, (6) prevention of DKA, (7) non-DKA states of fasting ketonemia and ketonuria, (8) potential integration of CKMs with pumps and automated insulin delivery systems to prevent DKA, (9) clinical trials of CKMs, and (10) the future of CKMs. The panelists summarized the medical literature for each of the ten topics in this report. They also developed 30 conclusions (amounting to three conclusions for each topic) about CKMs and voted unanimously to adopt the 30 conclusions. This report is intended to support the development of safe and effective continuous ketone monitoring and to apply this technology in ways that will benefit people with diabetes.
Published: 2021
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7. Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Author: Pisani, Luigi, Algera, Anna Geke, Neto, Ary Serpa, Azevedo, Luciano, Pham, Tài, Paulus, Frederique, de Abreu, Marcelo Gama, Pelosi, Paolo, Dondorp, Arjen M, Bellani, Giacomo, Laffey, John G, Schultz, Marcus J, Martinez, Amadeu, Leal, Livia, Jorge Pereira, Antonio, de Oliveira Maia, Marcelo, Neto, Josè Aires, Piras, Claudio, Caser, Eliana Bernadete, Moreira, Cora Lavigne, Braga Gusman, Pablo, Dalcomune, Dyanne Moysés, Ribeiro de Carvalho, Alexandre Guilherme, Gondim, Louise Aline Romão, Castelo Branco Reis, Lívia Mariane, da Cunha Ribeiro, Daniel, de Assis Simões, Leonardo, Campos, Rafaela Siqueira, Fernandez Versiani dos Anjos, José Carlos, Bruzzi Carvalho, Frederico, Alves, Rossine Ambrosio, Nunes, Lilian Batista, Réa-Neto, Álvaro, de Oliveira, Mirella Cristine, Tannous, Luana, Cardoso Gomes, Brenno, Rodriguez, Fernando Borges, Abelha, Priscila, Lugarinho, Marcelo E, Japiassu, Andre, de Melo, Hélder Konrad, Lopes, Elton Afonso, Varaschin, Pedro, de Souza Dantas, Vicente Cés, Freitas Knibel, Marcos, Ponte, Micheli, de Azambuja Rodrigues, Pedro Mendes, Costa Filho, Rubens Carmo, Saddy, Felipe, Wanderley Castellões, Théia Forny, Silva, Suzana Alves, Osorio, Luiz Antonio Gomes, Mannarino, Dora, Espinoza, Rodolfo, Righy, Cassia, Soares, Marcio, Salluh, Jorge, Tanaka, Lilian, Aragão, Daniel, Tavares, Maria Eduarda, Kehdi, Maura Goncalves Pereira, Rezende, Valéria Maria Campos, Carbonell, Roberto Carlos Cruz, Teixeira, Cassiano, de Oliveira, Roselaine Pinheiro, Maccari, Juçara Gasparetto, Castro, Priscylla Souza, Berto, Paula, Schwarz, Patricia, Torelly, André Peretti, Lisboa, Thiago, Moraes, Edison, Dal-Pizzol, Felipe, Tomasi Damiani, Cristiane, Ritter, Cristiane, Ferreira, Juliana Carvalho, Teixeira Costa, Ramon, Caruso, Pedro, Amendola, Cristina Prata, de Oliveira, Amanda Maria R R, Silva, Ulysses V A, Sanches, Luciana Coelho, Almeida, Rosana D S, Azevedo, Luciano Cesar, Park, Marcelo, Schettino, Guilherme, Assunção, Murillo Santucci, Silva, Eliezer, Barboza, 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Kiourtzieva, Ellada V, Oikonomou, Marina A, Avila, Luis E, Cortez, Cesar A, Citalán, Johanna E, Jog, Sameer A, Sable, Safal D, Shah, Bhagyesh, Gurjar, Mohan, Baronia, Arvind K, Memon, Mohammedfaruk, Muthuchellappan, Radhakrishnan, Ramesh, Venkatapura J, Shenoy, Anitha, Unnikrishnan, Ramesh, Dixit, Subhal B, Rhayakar, Rachana V, Ramakrishnan, Nagarajan, Bhardwaj, Vallish K, Mahto, Heera L, Sagar, Sudha V, Palaniswamy, Vijayanand, Ganesan, Deeban, Mohammadreza Hashemian, Seyed, Jamaati, Hamidreza, Heidari, Farshad, Meaney, Edel A, Nichol, Alistair, Knapman, Karl M, O'Croinin, Donall, Dunne, Eimhin S, Breen, Dorothy M, Clarkson, Kevin P, Jaafar, Rola F, Dwyer, Rory, Amir, Fahd, Ajetunmobi, Olaitan O, O'Muircheartaigh, Aogan C, Black, Colin S, Treanor, Nuala, Collins, Daniel V, Altaf, Wahid, Zani, Gianluca, Fusari, Maurizio, Spadaro, Savino, Volta, Carlo A, Graziani, Romano, Brunettini, Barbara, Palmese, Salvatore, Formenti, Paolo, Umbrello, Michele, Lombardo, Andrea, Pecci, Elisabetta, 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Shimizu, Kazuyoshi, Shiozaki, Kyoko, Futami, Satoru, Ryosuke, Sekine, Saito, Koji, Kameyama, Yoshinobu, Ueno, Keiko, Izawa, Masayo, Okuda, Nao, Suzuki, Hiroyuki, Harasawa, Tomofumi, Nasu, Michitaka, Takada, Tadaaki, Ito, Fumihito, Nunomiya, Shin, Koyama, Kansuke, Abe, Toshikazu, Andoh, Kohkichi, Kusumoto, Kohei, Hirata, Akira, Takaba, Akihiro, Kimura, Hiroyasu, Matsumoto, Shuhei, Higashijima, Ushio, Honda, Hiroyuki, Aoki, Nobumasa, Imai, Hiroshi, Ogino, Yasuaki, Mizuguchi, Ichiko, Ichikado, Kazuya, Nitta, Kenichi, Mochizuki, Katsunori, Hashida, Tomoaki, Tanaka, Hiroyuki, Nakamura, Tomoyuki, Niimi, Daisuke, Ueda, Takeshi, Kashiwa, Yozo, Uchiyama, Akinori, Sabelnikovs, Oleg, Oss, Peteri, Haddad, Youssef, Liew, Kong Y, Ñamendys-Silva, Silvio A, Jarquin-Badiola, Yves D, Sanchez-Hurtado, Luis A, Gomez-Flores, Saira S, Marin, Maria C, Villagomez, Asisclo J, Lemus, Jordana S, Fierro, Jonathan M, Cervantes, Mavy Ramirez, Mejia, Francisco Javier Flore, Gonzalez, Daniel R, Dector, Dulce M, 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H, Willett, Emma L, Ioannou, Nichola, Gillis, Sarah, Csabi, Peter, Macfadyen, Rosaleen, Dawson, Heidi, Preez, Pieter D, Williams, Alexandra J, Boyd, Owen, De Gordoa, Laura Ortiz-Ruiz, Bramall, Jon, Symmonds, Sophie, Chau, Simon K, Wenham, Tim, Szakmany, Tama, Toth-Tarsoly, Piroska, Mccalman, Katie H, Alexander, Peter, Stephenson, Lorraine, Collyer, Thoma, Chapman, Rhiannon, Cooper, Raphael, Allan, Russell M, Sim, Malcolm, Wrathall, David W, Irvine, Donald A, Zantua, Kim S, Adams, John C, Burtenshaw, Andrew J, Sellors, Gareth P, Welters, Ingeborg D, Williams, Karen E, Hessell, Robert J, Oldroyd, Matthew G, Battle, Ceri E, Pillai, Suresh, Kajtor, Istvan, Sivashanmugave, Mageswaran, Okane, Sinead C, Donnelly, Adrian, Frigyik, Aniko D, Careless, Jon P, May, Martin M, Stewart, Richard, Trinder, T John, Hagan, Samantha J, Wise, Matt P, Cole, Jade M, MacFie, Caroline C, Dowling, Anna T, Nin, Nicolá, Nuñez, Edgardo, Pittini, Gustavo, Rodriguez, Ruben, Imperio, María C, Santos, Cristina, França, Ana G, Ebeid, Alejandro, Deicas, Alberto, Serra, Carolina, Uppalapati, Aditya, Kamel, Ghassan, Banner-Goodspeed, Valerie M, Beitler, Jeremy R, Mukkera, Satyanarayana Reddy, Kulkarni, Shreedhar, Lee, Jarone, Mesar, Tomaz, Shinn Iii, John O, Gomaa, Dina, Tainter, Christopher, Cowley, R Adam, Yeatts, Dale J, Warren, Jessica, Lanspa, Michael J, Miller, Russel R, Grissom, Colin K, Brown, Samuel M, Bauer, Philippe R, Gosselin, Ryan J, Kitch, Barrett T, Cohen, Jason E, Beegle, Scott H, Gueret, Renaud M, Tulaimat, Aiman, Choudry, Shazia, Stigler, William, Batra, Hitesh, Huff, Nidhi G, Lamb, Keith D, Oetting, Trevor W, Mohr, Nicholas M, Judy, Claine, Saito, Shigeki, Kheir, Fayez M, Schlichting, Adam B, Delsing, Angela, Elmasri, Mary, Crouch, Daniel R, Ismail, Dina, Blakeman, Thomas C, Dreyer, Kyle R, Baron, Rebecca M, Grijalba, Carolina Quintana, Hou, Peter C, Seethala, Raghu, Aisiku, Imo, Henderson, Galen, Frendl, Gyorgy, Hou, Sen-Kuang, Owens, Robert L, Schomer, Ashley, Bumbasirevic, Vesna, Jovanovic, Bojan, Surbatovic, Maja, Veljovic, Milic, Rodgers, Helen, Dixon, Barry, Smith, Roger, Kol, Mark, Wong, Helen, Schmid, Werner, Hermans, Greet, Bourgeois, Marc, Anquez, Nathalie, Decruyenaere, Johan, DeCrop, Luc, Souza dos Santos, Rafaella, Beraldo, Daniel, dos Santos, Moreno Calcagnotto, Pellegrini, Jose Augusto Santo, Oliveira, Vanessa, Munhoz, Carlo, Peçanha, Ana Carolina, da Silva Ramos, Fernando José, Maia, Israel, Bahl, Marina, Biondi, Rodrigo, Prado, Daniel, Pinto, Sérgio Felix, Salgado, Jean, Falcão, Luis Fernando, Macruz, Tiago, Ruas, Kessia, Mecatti, Giovana Colozza, Caser, Eliane Bernadete, Gava, Isabela Ambrósio, Carreño, Nicolá, Morales, Mauricio, Avendaño, Rossana, Aguirre, Stefania, Sribar, Andrej, Klaric, Vlasta, Skilijic, Sonja, Dvorscak, Matea Bogdanovic, Krkusek, Marijana, Jurjevic, Matija, Karanovic, Nenad, Simurina, Tatjana, Stourac, Petr, Kratochvil, Milan, Schlegel, Christian, Treschan, Tanja A, Schaefer, Maximilian, Aytulun, Akut, Kienbaum, Peter, Jaafar, Rola, Collins, Daniel, Plant, Robert, Melchionda, Giuseppe, Di Lauro, Eduardo, Russotto, Vincenzo, Caione, Raffaele, Mestria, Donatella, Volta, Carlo Alberto, Seghelini, Elisa, Sales, Gabriele, D'Antini, Davide, Severgnini, Paolo, Bacuzzi, Alessandro, Peluso, Lorenzo, Verrastro, Pasquale, Raimondo, Pasquale, Gecaj-Gashi, Agreta, Tuinman, Pieter Roel, Alberts, Erna, van den Hul, Ingrid, Kuiper, Michael, de Wilde, Robert BP, Koopmans, Matty, Kose, Isil, Zincircioglu, Çiler, Dogan, Nazim, Aydin, Demet, Denker, Ahmet Sukru, Buyukkocak, Unase, Akgun, Nur, Turan, Güldem, Senturk, Evren, Demirtürk, Zerrin, Özcan, Perihan Ergin, Ekinci, Osman, Saylan, Sedat, Eren, Gulay, Ulger, Fatma, Dilek, Ahmet, Ulusoy, Hulya, Goktas, Ugur, Soyoral, Lokman, Toman, Huseyin, Orak, Yavuz, Kahveci, Feda, Mills, Gary H, Pinder, Angela, Walker, Rachel, Harrison, Jonathan, Snell, Jane, Pearson, Rachel, Sharman, Michael, Kaloo, Claire, Bynorth, Natalie, Matthews, Kelly, Hughes, Chloe, Rose, Alastair, Simeson, Karen, Niska, Lotta, Huneke, Nathan, Adderly, Jane, Padilla-Harris, Cheryl, Oliver, Rebecca, Brohi, Farooq, Wilson, Natalie, Talbot, Helen, Wilson, Deborah, Smith, Deborah, Dark, Paulo, Evans, Tracey, Fisher, Nicola, Montgomery, Jane, Fitzell, Pauline, Muench, Christoph, Hugill, Keith, Cirstea, Emanuel, Bentley, Andrew, Lynch, Katie, White, Ian, Cooper, Jonathan, Brazier, Melinda, Devile, Michael, Parris, Michael, Gill, Pardeep, Patel, Tasmin, Criswell, John, Trodd, Dawn, Griffin, Denise, Martin, Jane, Wreybrown, Caroline, Bewley, Jeremy, Sweet, Katie, Grimmer, Lisa, Kozlowski, Marta, James, Shanaz, Limb, Jame, Cowton, Amanda, Rogerson, David, Downes, Charlotte, Melbourne, Susan, Humphries, Ryan, Pulletz, Mark, Moreton, Sarah, Janes, Stephanie, Corner, Andrew, Linnett, Vanessa, Ritzema, Jenny, Watters, Malcolm, Windebank, Steve, Chenna, Shailaja, Howard-Griffin, Richard, Turner, Kate, Suresh, Sheeba, Blaylock, Heather, Bell, Stephanie, Blenk, Karl, Everett, Lynn, Hadfield, Daniel, Harris, Clair, Chan, Alexandre, Birch, Sian, Pegg, Claire, Plowright, Catherine, Cooper, Lucy, Hatton, Tom, McCullagh, Iain, Wright, Stephen, Scott, Carmen, Boyd, Christine, Holliday, Mark, Poultney, Una, Crowther, Hannah, Thornthwaite, Sarah, Hollister, Nigel, Hunt, Jane, Skinner, Amanda, Matsa, Ramprasad, Salt, Ruth, Matthews, Claire, Venner, Nicola, Barcraft-Barnes, Helena, Tbaily, Lee, Pogson, David, Mouland, Johanna, Rose, Steve, Lamb, Nicola, Tarmey, Nichola, Knighton, John, Giles, Julian, Weller, Debbie, Reed, Isabelle, Hormis, Anil, Pearson, Sallyane, Harris, Meredith, Howe, Joanne, Paddle, Jonathan, Burt, Karen, Welters, Ingeborg, Walker, Anna, Youds, Laura, Hendry, Sam, Shaw, David, Williams, Karen, Hollands, Robin, Carnahan, Mandy, Stickley, Johanna, Miller, Claire, Donaldson, Denise, Tonks, Louise, Creagh-Brown, Ben, Hull, Daniel, Ortiz-Ruiz, Laura, Gopal, Shammer, Metherell, Stella, Spencer, Hazel, Frey, Christian, Brown, Carly, Clifford, Gayle, Leaver, Susannah, Ryan, Christine, Mellinghoff, Johannes Mellinghoff, Prudden, Sarah Prudden, Green, Helen Green, Roy, Alistair Roy, Furneval, Julie Furneval, Bell, Adam Bell, Lakhani, Sandeep Lakhani, Fasting, Lousie Fasting, Murray, Lorna Murray, Preller, Kobu, McInerney, Amy, Beavis, Sarah, Whileman, Amanda, Toms, Julie, Glenn, Sue, Ramali, Mohamed, Ghosh, Alison, Bullock, Clare, Barrell, Lisa, Young, Eoin, Robertson, Helen, Faulkner, Maria, MacNaughton, Peter, Tyson, Susan, Pulak, Paul, Sewell, Terri-Ann, Smalley, Christopher, Jacob, Reni, Alzugaray, Pedro, Vidal Melo, Marcos F, Joyce, Kristen, Needleman, Joseph, Ahsan, Areef, Faiz, Abul, Alam, AKM Shamsul, Khatoon, Syeda Nafisa, Nath, Ranjan Kumer, Rahman Chowdhury, Mohammed Abdur, Banik, Debabrata, Mondol, Montosh Kumar, Bhuiyan, Sakibur Rahman, Nazneed, Suraiya, Sultana, Rozina, Hamid, Tarikul, Hossain, Mozaffer, Reza, Syed Tariq, Asaduzzaman, Muhammad, Salim, Mohammad, Mostafa Kamal, Abu Hena, Taher, Sheikh Mohammed, Taohid, Taohidul Majid, Karmaker, Pranab, Roy, Sabyasachi, Das, Shantanu, Sarkar, Sohel Ahmed, Dutta, Monju Lal, Roy, Poulomi, Iyer, Shivakumar, Krishna, Bhuvana, Sampath, Sriram, Pattnaik, Rajyabardhan, Kasi, Chinni Krishna, Shah, Jignesh, Dongre, Anand, Reza Hashemian, Seyed Mohammad, Nooraei, Navid, Raessi Estabragh, Reza, Malekmohammad, Majid, Khoundabi, Batoul, Mobasher, Maziar, Mohd Yunos, Nor'azim, Kassim, Mahazir, Voon, Chern Min, Das, Stanis Sutharsa, Azauddin, Siti Nur Suhaila, Dorasamy, Dharshinie, Tai, Li Ling, Mat Nor, Mohd Basri, Zarudin, Nurhafizah, Hasan, Mohd Shahnaz, Jamaluddin, Mohamad Fadhil Hadi, Othman Jailani, Mohamad Irfan, Kayashta, Gyan, Adhikari, Aaradhana, Pangeni, Raju, Hashmi, Madiha, Joseph, Sonia, Akhtar, Aftab, Qadeer, Aayesha, Memon, Iqbal, Ali, Syed Muneeb, Idrees, Farah, Kamal, Saima, Hanif, Sadaf, Rehman, Atta Ur, Taqi, Arshad, Hussain, Tanveer, Farooq, Ahmed, Khaskheli, Saleh, Hayat, Muhammad, Indraratna, Kanishka, Beane, Abigail, Haniffa, Rashan, Samaranayake, Upeka, Mathanalagan, Sathiyamoorthy, Gunaratne, Asoka, Mithraratne, Nimangee, Thilakasiri, Kaushila, Pilimatalawwe, Chamila, Dilhani, Y A Hasitha, Fernando, Marie, Ranatunge, Kumudini, Samarasinghe, Loranthi, Vaas, Manori, Edirisooriya, Manoj, Sigera, Chathurani, Arumoli, Janaki, De Silva, Kesharie, Kudavidanage, Bimal, Pinto, Visanthi, Dissanayake, Lakshman, Chittawatanarat, Kaweesak, Kongpolprom, Napplika, Silachamroon, Udomsak, Pornsuriyasak, Prapaporn, Petnak, Tananchai, Singhatas, Pongsasit, Tangsujaritvijit, Viratch, Rungruanghiranya, Suthat, Piriyapatsom, Annop, Juntaping, Kanokkarn, Trongtrakul, Konlawij, Thungtitigul, Poungrat, Tajarernmuang, Pattraporn, Chatmongkolchart, Sunisa, Bhurayanontachai, Rungsun, Akaraborworn, Osaree, Navasakulpong, Asma, Surasit, Karjbundid, Thwaites, Louise, Nadjm, Behzad, Vu Quoc, Dat, Nguyen Thi Thanh, Ha, Nguyen Van, Kinh, Duong Bich, Thuy, Lam Minh, Yen, Anesthesiology, Intensive care medicine, ACS - Pulmonary hypertension & thrombosis, ACS - Diabetes & metabolism, Graduate School, Intensive Care Medicine, AII - Inflammatory diseases, Nursing, and ACS - Microcirculation
Subjects: Male, Sociodemographic Factors, Respiration, Artificial/methods, ARDS, mechanical ventilation, Severity of Illness Index, NO, Settore MED/41 - ANESTESIOLOGIA, 80 and over, Tidal Volume, Humans, Hospital Mortality, Prospective Studies, ddc:610, Developing Countries, Aged, Hospital Mortality/trends, Aged, 80 and over, Developed Countries/statistics & numerical data, Developing Countries/statistics & numerical data, Respiration, Developed Countries, Articles, General Medicine, acute respiratory distress syndrome, Length of Stay, Middle Aged, Respiration, Artificial, Intensive Care Units, Observational Studies as Topic, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Length of Stay/statistics & numerical data, Artificial, Intensive Care Units/statistics & numerical data, Income, Female
Abstract: Contains fulltext : 252214.pdf (Publisher’s version ) (Open Access) BACKGROUND: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. METHODS: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. FINDINGS: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H(2)O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p
Published: 2022
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8. Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis

Author: Zhou Z., Jardine M. J., Li Q., Neuen B. L., Cannon C. P., De Zeeuw D., Edwards R., Levin A., Mahaffey K. W., Perkovic V., Neal B., Lindley R. I., Guerrero R. A. A., Aizenberg D., Albisu J. P., Alvarisqueta A., Bartolacci I., Berli M. A., Bordonava A., Calella P., Cantero M. C., Cartasegna L. R., Cercos E., Coloma G. C., Colombo H., Commendatore V., Cuadrado J., Cuneo C. A., Cusumano A. M., Douthat W. G., Dran R. D., Farias E., Fernandez M. F., Finkelstein H., Fragale G., Fretes J. O., Garcia N. H., Gastaldi A., Gelersztein E., Glenny J. A., Gonzalez J. P., Del Carmen Gonzalez Colaso P., Goycoa C., Greloni G. C., Guinsburg A., Hermida S., Juncos L. I., Klyver M. I., Kraft F., Krynski F., Lanchiotti P. V., De La Fuente R. A. L., Marchetta N., Mele P., Nicolai S., Novoa P. A., Orio S. I., Otreras F., Oviedo A., Raffaele P., Resk J. H., Rista L., Papini N. R., Sala J., Santos J. C., Schiavi L. B., Sessa H., Casabella T. S., Ulla M. R., Valdez M., Vallejos A., Villarino A., Visco V. E., Wassermann A., Zaidman C. J., Cheung N. W., Droste C., Fraser I., Johnson D., Mah P. M., Nicholls K., Packham D., Proietto J., Roberts A., Roger S., Tsang V., Raduan R. A., Da Costa F. A. A., Amodeo C., Turatti L. A. A., Bregman R., Sanches F. C. C., Canani L. H., Chacra A. R., Borges J. L. C., Vencio S. A. C., Da Silva Franco R. J., D'Avila D., De Souza Portes E., De Souza P., Deboni L. M., Filho F. F., Neto B. G., Gomes M., Kohara S. K., Keitel E., Saraiva J. F. K., Lisboa H. R. K., De Carvalho Contieri F. L., Milagres R., Junior R. M., De Brito C. M., Hissa M. N., Sabbag A. R. N., Noronha I., Panarotto D., Filho R. P., Pereira M. A., Saporito W., Scotton A. S., Schuch T., De Almeida R. S., Ramos C. S., Felicio J. S., Thome F., Hachmann J. C. T., Yamada S., Hayashida C. Y., Petry T. B. Z., Zanella M. T., Andreeva V., Angelova A., Dimitrov S., Genadieva V., Genova-Hristova G., Hristozov K., Kamenov Z., Koundurdjiev A., Lozanov L., Margaritov V., Nonchev B., Rangelov R., Shinkov A., Temelkova M., Velichkova E., Yakov A., Aggarwal N., Aronson R., Bajaj H., Cherney D., Chouinard G., Conway J., Cournoyer S., DaRoza G., De Serres S., Dube F., Goldenberg R., Gupta A., Gupta M., Henein S., Khandwala H., Leiter L., Madore F., Mc-Mahon A., Muirhead N., Pichette V., Rabasa-Lhoret R., Steele A., Tangri N., Torshizi A., Woo V., Zalunardo N., Montenegro M. A. F., Jorquera J. G. G., Farina M. M., Gajardo V. S., Vejar M., Chen N., Chen Q., Gan S., Kong Y., Li D., Li W., Li X., Lin H., Liu J., Lu W., Mao H., Ren Y., Song W., Sun J., Sun L., Tu P., Wang G., Yang J., Yin A., Yu X., Zhao M., Zheng H., Mendoza J. L. A., Arcos E., Avendano J., Ruiz J. E. A. D., Ortiz L. H. G., Gonzalez A., Triana E. H., Higuera J. D., Malaver N., De Salazar D. I. M., Rosero R., Lozano M. A. T., Cometa L. V., Valenzuela A., Alonso R. D. V., Villegas I., Yupanqui H., Bartaskova D., Barton P., Belobradkova J., Dohnalova L., Drasnar T., Ferkl R., Halciakova K., Klokocnikova V., Kovar R., Lastuvka J., Lukac M., Pesickova S., Peterka K., Pumprla J., Rychlik I., Saudek F., Tesar V., Valis M., Weiner P., Zemek S., Alamartine E., Borot S., Cariou B., Dussol B., Fauvel J. -P., Gourdy P., Klein A., Le Meur Y., Penfornis A., Roussel R., Saulnier P. -J., Thervet E., Zaoui P., Burst V., Faghih M., Faulmann G., Haller H., Jerwan-Keim R., Maxeiner S., Paschen B., Plassmann G., Rose L., Orellana R. A. G., Haase F. P., Diaz J. P. M., Roca L. A. R., Arenales J. A. S., Polo J. V. S., Juarez E. T., Csecsei G., Csiky B., Danos P., Deak L., Dudas M., Harcsa E., Keltai K., Keresztesi S., Kiss K., Konyves L., Major L., Mileder M., Molnar M., Mucsi J., Oroszlan T., Ory I., Paragh G., Peterfai E., Petro G., Revesz K., Takacs R., Vangel S., Vasas S., Zsom M., Oomman A., Raju S. B., Dewan D., Fernando M. 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M., El-Shahawy M., Ervin J., Esquenazi A., Evans J., Fishbane S., Frias J., Galindo-Ramos E., Galphin C., Ghazi A., Gonzalez E., Gorson D., Gowda A., Greco B., Grubb S., Gulati R., Hammoud J., Handelsman S., Hartman I., Hershon K., Hiser D., Hon G., Jacob R., Jaime M., Jamal A., Kaupke C., Keightley G., Kern E., Khanna R., Khitan Z., Kim S., Kopyt N., Kovesdy C., Krishna G., Kropp J., Kumar A., Kumar J., Kumar N., Kusnir J., Lane W., Lawrence M., Lehrner L., Lentz J., Levinson D., Lewis D., Liss K., Maddux A., Maheshwari H., Mandayam S., Marar I., Mehta B., Middleton J., Mordujovich J., Moreda R., Moustafa M., Trenche S. M., Narayanan M., Narvarte J., Nassar T., Newman G., Nichol B., Nicol P., Nisnisan J., Nossuli A. 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Subjects: medicine.medical_specialty, Original Contributions, atrial fibrillation, canagliflozin, glomerular filtration rate, hemorrhagic stroke, ischemic stroke, Renal function, Disease, Brain Ischemia, Clinical and Population Sciences, Meta-Analysis as Topic, Internal medicine, CREDENCE Trial Investigators, Atrial Fibrillation, medicine, Diabetes Mellitus, Humans, Diabetic Nephropathies, Canagliflozin, Stroke, 1102 Cardiorespiratory Medicine and Haematology, Sodium-Glucose Transporter 2 Inhibitors, Advanced and Specialized Nursing, Neurology & Neurosurgery, business.industry, Atrial fibrillation, 1103 Clinical Sciences, medicine.disease, Diabetes Mellitus, Type 2, Meta-analysis, Cardiology, Albuminuria, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine, business, 1109 Neurosciences, Kidney disease, medicine.drug
Abstract: Supplemental Digital Content is available in the text., Background and Purpose: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. Methods: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis. Results: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55–1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61–1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19–1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20–1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53–1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82–1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89–1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30–0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49–1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71–0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (
Published: 2021

9. Outcome of acute hypoxaemic respiratory failure: insights from the LUNG SAFE Study

Author: Pham, Tài, Pesenti, Antonio, Bellani, Giacomo, Rubenfeld, Gordon, Fan, Eddy, Bugedo, Guillermo, Lorente, José Angel, Fernandes, Antero do Vale, Van Haren, Frank, Bruhn, Alejandro, Rios, Fernando, Esteban, Andres, Gattinoni, Luciano, Larsson, Anders, McAuley, Daniel F., Ranieri, Marco, Thompson, B. Taylor, Wrigge, Hermann, Brochard, Laurent J., Laffey, John G, Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Lise Piquilloud, Fekri Abroug, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid Bin Hj Abul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Boris G Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, HansBernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, Eimhin S Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, Colin S Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, 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Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan 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Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin 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Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Nicolás Nin, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, 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Angel, Fernandes, Antero do Vale, Van Haren, Frank, Bruhn, Alejandro, Rios, Fernando, Esteban, Andre, Gattinoni, Luciano, Larsson, Ander, McAuley, Daniel F., Ranieri, Marco, Thompson, B. Taylor, Wrigge, Hermann, Brochard, Laurent J., Laffey, John G, Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, John G Laffey, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Frank van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Hermann Wrigge, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Anders Larsson, Lise Piquilloud, Fekri Abroug, Daniel F McAuley, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Pieter Depuydt, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid Bin Hj Abul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Haibo Qiu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Jonas Nielsen, Boris G Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Tài Pham, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, HansBernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L 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Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori 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C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Lise Piquilloud, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Lia McNamee, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Javier Hurtado, Nicolás Nin, Javier Hurtado, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Daniel R Crouch, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Dina Gomaa, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, Intensive Care Medicine, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, ACS - Microcirculation, Pham, T, Pesenti, A, Bellani, G, Rubenfeld, G, Fan, E, Bugedo, G, Lorente, J, Fernandes, A, Van Haren, F, Bruhn, A, Rios, F, Esteban, A, Gattinoni, L, Larsson, A, Mcauley, D, Ranieri, M, Thompson, B, Wrigge, H, Brochard, L, Laffey, J, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), St. Michael's Hospital, University of Toronto, Groupe de recherche clinique CARMAS, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano [Milano] (UNIMI), University of Milan, San Gerardo Hospital, Sunnybrook Health Sciences Center, Mount Sinai Hospital [Toronto, Canada] (MSH), Pontificia Universidad Católica de Chile (UC), University Hospital of Getafe, CIBER Enfermedades Respiratorias (CIBERES), Universidad Europea de Madrid, Hospital Garcia de Orta (EPE), Canberra Hospital, Medical School [Australian National University - ANU], Australian National University (ANU), University of Canberra, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of Göttingen - Georg-August-Universität Göttingen, Uppsala University, Queen's University [Belfast] (QUB), Royal Victoria Hospital, McGill University Health Center [Montreal] (MUHC), Università degli Studi di Bologna, Massachusetts General Hospital [Boston], University Hospital Leipzig, Department of Anaesthesiology, Intensive Care and Emergency Medicine, Pain Therapy, Bergmannstrost Hospital Halle, 06112, Halle, National University of Ireland [Galway] (NUI Galway), Bayer GlaxoSmithKline, GSK Baxter International Boehringer Ingelheim Wellcome Trust, WT National Institute for Health Research, NIHR Queen's University Belfast, QUB Medical Research Council Canada, MRC European Society of Intensive Care Medicine, ESICM, Support statement: This work was supported by the European Society of Intensive Care Medicine. Funding information for this article has been deposited with the Crossref Funder Registry., Conflict of interest: T. Pham has nothing to disclose. A. Pesenti reports personal fees from Maquet, Novalung/Xenios, Baxter, Gilead and Boehringer Ingelheim, outside the submitted work. G. Bellani reports grants and personal fees from Draeger Medical, personal fees from Getinge, Hamilton, GE Healthcare, Dimar SRL, Intersurgical and Flowmeter SPA, outside the submitted work. G. Rubenfeld has nothing to disclose. E. Fan reports personal fees from ALung Technologies, Getinge and MC3 Cardiopulmonary, grants, personal fees and non-financial support from Fresenius Medical Care, outside the submitted work. G. Bugedo has nothing to disclose. J.A. Lorente has nothing to disclose. A.D. V. Fernandes has nothing to disclose. F. Van Haren has nothing to disclose. A. Bruhn has nothing to disclose. F. Rios has nothing to disclose. A. Esteban has nothing to disclose. L. Gattinoni has nothing to disclose. A. Larsson reports grants from the Swedish Heart and Lung Foundation, during the conduct of the study. D.F. McAuley reports personal fees from consultancy for GlaxoSmithKline, Boehringer Ingelheim and Bayer, outside the submitted work, in addition, his institution has received funds from grants from the UK NIHR, Wellcome Trust, Innovate UK, NI HSC R&D Division, NI Chest Heart and Stroke, and MRC, is one of four named inventors on a patent US8962032 covering the use of sialic acid-bearing nanoparticles as anti-inflammatory agents issued to his institution, The Queen’s University of Belfast (http://www.google.com/patents/US8962032), and is a Director of Research for the Intensive Care Society and NIHR EME Programme Director. M. Ranieri has nothing to disclose. B.T. Thompson reports personal fees from Bayer, Thetis and Novartis, outside the submitted work. H. Wrigge reports personal fees for consultancy from Dräger Medical, personal fees for advisory board work from Liberate Medical, grants and personal fees for lectures from InfectoPharm, personal fees for lectures from MSD and GE, outside the submitted work. L.J. Brochard reports grants from Medtronic Covidien, grants and non-financial support from Fisher Paykel, non-financial support from Air Liquide, Sentec and Philips, other (patent) from General Electric, outside the submitted work. J.G. Laffey reports grants and personal fees from Baxter, grants and non-financial support from Aerogen and Factor Biosciences, outside the submitted work., LUNG SAFE Investigators and the European Society of Intensive Care Medicine Trials Group: Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, John G Laffey, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Frank van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Hermann Wrigge, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Anders Larsson, Lise Piquilloud, Fekri Abroug, Daniel F McAuley, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J 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Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Amine Ali Zeggwagh, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Leo M Heunks, Hellen M van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L RuizAguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana TempranoSusana, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Lise Piquilloud, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Lia McNamee, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Javier Hurtado, Nicolás Nin, Javier Hurtado, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Daniel R Crouch, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Dina Gomaa, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (MGD) Services des soins intensifs, and UCL - (SLuc) Service de soins intensifs
Subjects: Pulmonary and Respiratory Medicine, ARDS, Unidades de cuidados intensivos, [SDV]Life Sciences [q-bio], medicine.medical_treatment, mechanical ventilation, NO, law.invention, 03 medical and health sciences, Tratamiento médico, 0302 clinical medicine, law, Settore MED/41 - ANESTESIOLOGIA, Insuficiencia respiratoria, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Lung, Mechanical ventilation, Respiratory Distress Syndrome, business.industry, Respiration, Incidence (epidemiology), medicine.disease, Intensive care unit, Respiration, Artificial, 3. Good health, Intensive Care Units, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], medicine.anatomical_structure, 030228 respiratory system, Respiratory failure, Heart failure, Anesthesia, Artificial, ards, business, Respiratory Insufficiency, Enfermedad
Abstract: BackgroundCurrent incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in the intensive care unit (ICU) are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS).MethodsAn international, multicentre, prospective cohort study of patients presenting with hypoxaemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with arterial oxygen tension/inspiratory oxygen fraction ratio ≤300 mmHg, new pulmonary infiltrates and need for mechanical ventilation with a positive end-expiratory pressure of ≥5 cmH2O. ICU prevalence, causes of hypoxaemia, hospital survival and factors associated with hospital mortality were measured. Patients with unilateral versus bilateral opacities were compared.Findings12 906 critically ill patients received mechanical ventilation and 34.9% with hypoxaemia and new infiltrates were enrolled, separated into ARDS (69.0%), unilateral infiltrate (22.7%) and congestive heart failure (CHF; 8.2%). The global hospital mortality was 38.6%. CHF patients had a mortality comparable to ARDS (44.1% versus 40.4%). Patients with unilateral-infiltrate had lower unadjusted mortality, but similar adjusted mortality compared to those with ARDS. The number of quadrants on chest imaging was associated with an increased risk of death. There was no difference in mortality comparing patients with unilateral-infiltrate and ARDS with only two quadrants involved.InterpretationMore than one-third of patients receiving mechanical ventilation have hypoxaemia and new infiltrates with a hospital mortality of 38.6%. Survival is dependent on the degree of pulmonary involvement whether or not ARDS criteria are reached.
Published: 2021
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10. Severity modeling of propionic acidemia using clinical and laboratory biomarkers

Author: Susan Ferry, Oleg A Shchelochkov, Olivia Wenger, Paul Juneau, Samantha McCoy, Jeffrey B. Kopp, Mark D. Levin, Charles P. Venditti, Alexandra Pass, Irini Manoli, Laryssa A. Huryn, Megan Schoenfeld, Joseph Snow, Audrey Thurm, Colby Chlebowski, Wadih M. Zein, Kong Y. Chen, Jennifer L. Sloan, Jennifer Myles, and Carol Van Ryzin
Subjects: Oncology, medicine.medical_specialty, Propionic Acidemia, business.industry, medicine.disease, Article, Liver Transplantation, Clinical trial, Patient population, Text mining, Internal medicine, medicine, Humans, GDF15, Propionic acidemia, business, Laboratories, Genetics (clinical), Biomarkers
Abstract: To conduct a proof-of-principle study to identify subtypes of propionic acidemia (PA) and associated biomarkers. Data from a clinically diverse PA patient population ( https://clinicaltrials.gov/ct2/show/NCT02890342 ) were used to train and test machine learning models, identify PA-relevant biomarkers, and perform validation analysis using data from liver-transplanted participants. k-Means clustering was used to test for the existence of PA subtypes. Expert knowledge was used to define PA subtypes (mild and severe). Given expert classification, supervised machine learning (support vector machine with a polynomial kernel, svmPoly) performed dimensional reduction to define relevant features of each PA subtype. Forty participants enrolled in the study; five underwent liver transplant. Analysis with k-means clustering indicated that several PA subtypes may exist on the biochemical continuum. The conventional PA biomarkers, plasma total 2-methylctirate and propionylcarnitine, were not statistically significantly different between nontransplanted and transplanted participants motivating us to search for other biomarkers. Unbiased dimensional reduction using svmPoly revealed that plasma transthyretin, alanine:serine ratio, GDF15, FGF21, and in vivo 1-13C-propionate oxidation, play roles in defining PA subtypes. Support vector machine prioritized biomarkers that helped classify propionic acidemia patients according to severity subtypes, with important ramifications for future clinical trials and management of PA.
Published: 2021

11. Changes in sleep and activity from age 15 to 17 in students with traditional and college-style school schedules

Author: Robert J. Brychta, Kong Y. Chen, Sigridur Gudmundsdottir, Sunna Gestsdottir, Vaka Rognvaldsdottir, Erlingur Johannsson, and Runa Stefansdottir
Subjects: Male, Longitudinal study, Time Factors, Adolescent, education, Physical activity, Article, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, Humans, Medicine, Longitudinal Studies, 030212 general & internal medicine, Students, Exercise, Schools, business.industry, Age Factors, Actigraphy, Sleep in non-human animals, Female, Sleep, business, 030217 neurology & neurosurgery, Demography, Sleep duration
Abstract: OBJECTIVES: Sleep duration and physical activity decline with age during adolescence. Earlier school schedules may contribute to these declines. The aim of this longitudinal study was to track changes in sleep and activity of Icelandic youth from primary to secondary school and compare students who enrolled in secondary schools with traditional and college-style schedules. METHODS: We measured free-living sleep and activity with wrist actigraphy and body composition by dual-energy x-ray absorptiometry in 145 students at age 15 and age 17, when 58% attended schools with college-style scheduling. Differences from 15 to 17 and between students of different school structures were assessed with mixed-effect models. RESULTS: Actigraphs were worn for 7.1±0.4 nights at 15 and 6.9±0.4 nights at 17. Overall, sleep duration decreased from 6.6±0.7 h/night to 6.2±0.7 h/night from age 15 to 17 (p
Published: 2020
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12. Whole-Exon Sequencing and Correlation Analysis of a 14-Month-Old Girl With Orofaciodigital Syndrome

Author: Si L. Li, Kong Y. Li, and Yong Q. Wang
Subjects: Cleft Palate, Otorhinolaryngology, Face, Limb Deformities, Congenital, Humans, Surgery, Female, General Medicine, Exons, Orofaciodigital Syndromes
Abstract: Orofaciodigital syndrome type 1 (OFDS1) is a genetic disorder characterized by specific oral, facial, and limb malformations. A 14-month-old girl with congenital cleft palate, lower lip midline cleft, and digital anomalies admitted to our hospital was preliminarily diagnosed with OFDS1. Genetic analysis revealed that she carried a heterozygous variant of OFD1 at locus Xp22.2 on the X chromosome. Herein, we present the specific phenotype and genotype and the treatment modalities for this patient and references for diagnosing and treating OFDS.
Published: 2022

13. Postprandial plasma lipidomics reveal specific alteration of hepatic-derived diacylglycerols in non-alcoholic fatty liver disease

Author: Thomas J. Velenosi, Gil Ben-Yakov, Maren C. Podszun, Julian Hercun, Ohad Etzion, Shanna Yang, Cathy Nadal, Vanessa Haynes-Williams, Wen-Chun A. Huang, Lila González-Hódar, Robert J. Brychta, Shogo Takahashi, Vikas Akkaraju, Kristopher W. Krausz, Mary Walter, Hongyi Cai, Peter J. Walter, Ranganath Muniyappa, Kong Y. Chen, Frank J. Gonzalez, and Yaron Rotman
Subjects: Diglycerides, Mice, Hepatology, Liver, Non-alcoholic Fatty Liver Disease, Lipidomics, Gastroenterology, Insulins, Animals, Humans, Prospective Studies, Article
Abstract: Hepatic energy metabolism is a dynamic process modulated by multiple stimuli. In nonalcoholic fatty liver disease (NAFLD), human studies typically focus on the static fasting state. We hypothesized that unique postprandial alterations in hepatic lipid metabolism are present in NAFLD.In a prospective clinical study, 37 patients with NAFLD and 10 healthy control subjects ingested a standardized liquid meal with pre- and postprandial blood sampling. Postprandial plasma lipid kinetics were characterized at the molecular lipid species level by untargeted lipidomics, cluster analysis, and lipid particle isolation, then confirmed in a mouse model.There was a specific increase of multiple plasma diacylglycerol (DAG) species at 4 hours postprandially in patients with NAFLD but not in controls. This was replicated in a nonalcoholic steatohepatitis mouse model, where postprandial DAGs increased in plasma and concomitantly decreased in the liver. The increase in plasma DAGs appears early in the disease course, is dissociated from NAFLD severity and obesity, and correlates with postprandial insulin levels. Immunocapture isolation of very low density lipoprotein in human samples and stable isotope tracer studies in mice revealed that elevated postprandial plasma DAGs reflect hepatic secretion of endogenous, rather than meal-derived lipids.We identified a selective insulin-related increase in hepatic secretion of endogenously derived DAGs after a mixed meal as a unique feature of NAFLD. DAGs are known to be lipotoxic and associated with atherosclerosis. Although it is still unknown whether the increased exposure to hepatic DAGs contributes to extrahepatic manifestations and cardiovascular risk in NAFLD, our study highlights the importance of extending NAFLD research beyond the fasting state.
Published: 2022

14. The Effects of Interrupting Sitting Time on Affect and State Anxiety in Children of Healthy Weight and Overweight: A Randomized Crossover Trial

Author: Kevin P. Smith, Shanna Bernstein, Faizah Shareef, Kong Y. Chen, Jacob D. Hattenbach, Pamela L. Wolters, Sheila M. Brady, Ira L. Tigner, Robert J. Brychta, David Berrigan, Amber B. Courville, Jack A. Yanovski, Alexia Papachristopoulou, Bart Drinkard, Jennifer Zink, Douglas R. Rosing, Britni R. Belcher, and Miranda M. Broadney
Subjects: Male, Pediatric Obesity, medicine.medical_specialty, Time Factors, 030209 endocrinology & metabolism, Physical Therapy, Sports Therapy and Rehabilitation, Walking, Anxiety, Overweight, Sitting, Affect (psychology), Article, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Orthopedics and Sports Medicine, 030212 general & internal medicine, Child, Sitting Position, Cross-Over Studies, Maryland, business.industry, Body Weight, Repeated measures design, Crossover study, Confidence interval, Affect, Mood, Pediatrics, Perinatology and Child Health, Physical therapy, Female, Sedentary Behavior, medicine.symptom, business
Abstract: Purpose: Sedentary time relates to higher anxiety and more negative affect in children. This study assessed whether interrupting sitting over 3 hours is sufficient to influence state anxiety, positive affect, or negative affect, and tested weight status as a moderator. Methods: Analyses were the second (preplanned) purpose of a larger study. Children (N = 61; age: mean [SD] = 9.5 [1.3]; 43% healthy weight) completed 2 experimental conditions: continuous sitting for 3 hours and sitting for 3 hours interrupted with walking for 3 minutes in every 30 minutes. State anxiety, positive affect, and negative affect were reported at pretest and posttest. Multilevel models for repeated measures assessed whether experimental condition predicted posttest scores. Results: Experimental condition was unrelated to posttest state anxiety or positive affect. Weight status moderated how experimental condition influenced posttest negative affect (P = .003). Negative affect was lower in the children of healthy weight after interrupted sitting (vs continuous sitting; β = −0.8; 95% confidence interval, −1.5 to 0.0, P = .05), but it was higher in the children with overweight/obesity after interrupted sitting (vs continuous sitting; β = 0.6; 95% confidence interval, 0.0 to 1.2, P = .06). Conclusions: Interrupting sitting acutely reduced negative affect in children of healthy weight, but not in children with overweight. Further research is needed to better understand the potential emotional benefits of sitting interruptions in youth.
Published: 2020
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15. Targeting neutrophils using novel drug delivery systems in chronic respiratory diseases

Author: Gaurav Gupta, Ridhima Wadhwa, Philip M. Hansbro, Lim W. Yee, Keshav Raj Paudel, Leong S. Jean, Kamal Dua, Murtaza M. Tambuwala, Harish Dureja, Kishen Kunalan, Lee X. Wie, Kong Y. Xuan, Lee Y. Ying, Dinesh Kumar Chellappan, Monica Gulati, Mateus Webba da Silva, Saurabh Satija, Lim C. Rou, Jestin Chellian, Sachin Kumar Singh, and Meenu Mehta
Subjects: Neutrophils, Respiratory Tract Diseases, Inflammation, Cystic fibrosis, Pathogenesis, 03 medical and health sciences, Drug Delivery Systems, 0302 clinical medicine, Immune system, Therapeutic index, Drug Discovery, medicine, Animals, Humans, Pharmacology & Pharmacy, Asthma, business.industry, Neutrophil extracellular traps, medicine.disease, Oxidative Stress, Immune System, 030220 oncology & carcinogenesis, Chronic Disease, Drug delivery, Immunology, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: © 2020 Wiley Periodicals, Inc. Neutrophils are essential effector cells of immune system for clearing the extracellular pathogens during inflammation and immune reactions. Neutrophils play a major role in chronic respiratory diseases. In respiratory diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, lung cancer and others, there occurs extreme infiltration and activation of neutrophils followed by a cascade of events like oxidative stress and dysregulated cellular proteins that eventually result in apoptosis and tissue damage. Dysregulation of neutrophil effector functions including delayed neutropil apoptosis, increased neutrophil extracellular traps in the pathogenesis of asthma, and chronic obstructive pulmonary disease enable neutrophils as a potential therapeutic target. Accounting to their role in pathogenesis, neutrophils present as an excellent therapeutic target for the treatment of chronic respiratory diseases. This review highlights the current status and the emerging trends in novel drug delivery systems such as nanoparticles, liposomes, microspheres, and other newer nanosystems that can target neutrophils and their molecular pathways, in the airways against infections, inflammation, and cancer. These drug delivery systems are promising in providing sustained drug delivery, reduced therapeutic dose, improved patient compliance, and reduced drug toxicity. In addition, the review also discusses emerging strategies and the future perspectives in neutrophil-based therapy.
Published: 2020
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16. Opportunities and challenges in the therapeutic activation of human energy expenditure and thermogenesis to manage obesity

Author: Laura A. Fletcher, Hannah J. Lea, Thomas M. Cassimatis, Kong Y. Chen, Kenneth Y. Zhu, Joyce D. Linderman, Robert J. Brychta, Alana E O'Mara, Aaron M. Cypess, Nikita Sanjay Israni, Zahraa Abdul Sater, James W. Johnson, and Cheryl Cero
Subjects: 0301 basic medicine, Oxidative phosphorylation, Mitochondrion, Bioinformatics, Biochemistry, Oxidative Phosphorylation, 03 medical and health sciences, chemistry.chemical_compound, Adipose Tissue, Brown, Adipocyte, Receptors, Adrenergic, beta, Brown adipose tissue, medicine, Humans, Obesity, Molecular Biology, 030102 biochemistry & molecular biology, business.industry, JBC Reviews, Body Weight, Disease Management, Thermogenesis, Cell Biology, medicine.disease, Thermogenin, Mitochondria, 030104 developmental biology, medicine.anatomical_structure, chemistry, Energy expenditure, Energy Intake, Energy Metabolism, business
Abstract: The current obesity pandemic results from a physiological imbalance in which energy intake chronically exceeds energy expenditure (EE), and prevention and treatment strategies remain generally ineffective. Approaches designed to increase EE have been informed by decades of experiments in rodent models designed to stimulate adaptive thermogenesis, a long-term increase in metabolism, primarily induced by chronic cold exposure. At the cellular level, thermogenesis is achieved through increased rates of futile cycling, which are observed in several systems, most notably the regulated uncoupling of oxidative phosphorylation from ATP generation by uncoupling protein 1, a tissue-specific protein present in mitochondria of brown adipose tissue (BAT). Physiological activation of BAT and other organ thermogenesis occurs through β-adrenergic receptors (AR), and considerable effort over the past 5 decades has been directed toward developing AR agonists capable of safely achieving a net negative energy balance while avoiding unwanted cardiovascular side effects. Recent discoveries of other BAT futile cycles based on creatine and succinate have provided additional targets. Complicating the current and developing pharmacological-, cold-, and exercise-based methods to increase EE is the emerging evidence for strong physiological drives toward restoring lost weight over the long term. Future studies will need to address technical challenges such as how to accurately measure individual tissue thermogenesis in humans; how to safely activate BAT and other organ thermogenesis; and how to sustain a negative energy balance over many years of treatment.
Published: 2020
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17. Activating Human Adipose Tissue with the β3-Adrenergic Agonist Mirabegron

Author: Kong Y, Chen, Robert J, Brychta, Nikita S, Israni, Alex, Jiang, Hannah J, Lea, Taylor N, Lentz, Anne E, Pierce, and Aaron M, Cypess
Subjects: Thiazoles, Adipose Tissue, Brown, Fluorodeoxyglucose F18, Positron Emission Tomography Computed Tomography, Humans, Acetanilides, Adrenergic beta-Agonists
Abstract: An appealing strategy for treatment of metabolic disease in humans is activation of brown adipose tissue (BAT), a thermogenic organ best visualized through
Published: 2022

18. Screen Time and Body Image in Icelandic Adolescents: Sex-Specific Cross-Sectional and Longitudinal Associations

Author: Soffia M. Hrafnkelsdottir, Robert J. Brychta, Vaka Rognvaldsdottir, Kong Y. Chen, Erlingur Johannsson, Sigridur L. Guðmundsdottir, and Sigurbjorn A. Arngrimsson
Subjects: Male, screen time, body image, adolescents, longitudinal association, sex-specific analysis, Adolescent, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, Cross-Sectional Studies, Surveys and Questionnaires, Humans, Medicine, Female, Television
Abstract: Studies of adolescent body image and screen use are mostly limited to girls, and longitudinal data are scarce. We examined cross-sectional and longitudinal associations between these variables in mid-adolescent boys and girls. Data was collected when participants were at age 15 and 17, by questionnaire and objective measurements (n = 152 had complete data). Sex-specific linear regression was used to explore cross-sectional and longitudinal associations of self-reported screen use (total use, and time spent in gaming, TV/DVD/internet-based watching and internet use for communication) and body image, adjusting for vigorous physical activity, symptoms of depression, and body composition. Screen time was negatively associated with body image at both time points, although more strongly at age 15, and for girls only. Gaming and TV/DVD/internet watching was more strongly associated with body image than internet use for communication. Girls with above median screen time at both ages had 14% lower body image score at age 17 than girls with below median screen time at both time points. Our results suggest that screen use is likely to play a role in the development of body dissatisfaction among adolescent females. Limiting screen time may, therefore, help to mitigate body dissatisfaction in adolescent girls.
Published: 2022

19. Sleep timing and consistency are associated with the standardised test performance of Icelandic adolescents

Author: Runa Stefansdottir, Vaka Rognvaldsdottir, Erlingur Johannsson, Robert J. Brychta, and Kong Y. Chen
Subjects: Male, medicine.medical_specialty, Adolescent, Cognitive Neuroscience, Academic achievement, Affect (psychology), Bedtime, 03 medical and health sciences, Behavioral Neuroscience, Cognition, 0302 clinical medicine, Interquartile range, medicine, Humans, Students, Public health, General Medicine, Sleep in non-human animals, language.human_language, 030228 respiratory system, Physical therapy, language, Educational Status, Female, Self Report, Sleep, Icelandic, 030217 neurology & neurosurgery
Abstract: Sleep has been shown to affect cognitive function in laboratory studies; however, its association to the academic performance of adolescents has largely been demonstrated using self-reported measures. Studies with objective measures of both sleep and academic performance are limited. The aim of the present study was to determine whether the free-living sleep quantity, quality, and timing of 15-year-old adolescents measured with wrist actiography are associated with their scores on national standardised examinations as an objective measure of academic achievement. We measured sleep with wrist actiography for 1 week in 253 (150 girls) Icelandic adolescents with a mean (SD) age of 15.9 (0.3) years. Multiple linear regression was used to assess associations between sleep parameters and combined standardised examination scores in mathematics, English, and Icelandic obtained from the Icelandic Directorate of Education. We found that students went to bed at 00:49 hours (± 51.8 min) and slept for a mean (SD) of 6.6 (0.7) hr/night, with a median (interquartile range) night-to-night variation in sleep duration of 1.2 (0.7) hr and an efficiency of 88.1 (5.3)%. Combined analyses adjusted for sex, demonstrated that both bedtime and night-to-night variability in total sleep time were negatively associated with the average score across all topics. Sex-specific associations did not indicate clear differences between boys and girls. These findings suggest that, in addition to appropriate sleep duration, public health guidance should also highlight the importance of early and consistent sleep schedules to academic achievement for both boys and girls.
Published: 2021
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20. Indirect Effects of a Cognitive-Behavioral Intervention on Adolescent Weight and Insulin Resistance Through Decreasing Depression in a Randomized Controlled Trial

Author: Lauren D. Gulley, Jack A. Yanovski, Marian Tanofsky-Kraff, Cara H. Olsen, Lauren B. Shomaker, Kong Y. Chen, Eric Stice, and Nichole R. Kelly
Subjects: medicine.medical_specialty, Intervention Studies, Adolescent, medicine.medical_treatment, 030209 endocrinology & metabolism, Type 2 diabetes, Overweight, Body Mass Index, law.invention, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Randomized controlled trial, law, Diabetes mellitus, Internal medicine, Developmental and Educational Psychology, medicine, Humans, Obesity, 030212 general & internal medicine, Child, Depression (differential diagnoses), Depressive Disorder, Cognitive Behavioral Therapy, Depression, business.industry, Insulin, Body Weight, medicine.disease, Treatment Outcome, Pediatrics, Perinatology and Child Health, Psychotherapy, Group, Female, Insulin Resistance, medicine.symptom, business, Body mass index
Abstract: Objective Depression is linked to excess weight, insulin resistance, and type 2 diabetes (T2D). We previously reported that in adolescent girls at-risk for T2D with moderately elevated depression, randomization to cognitive-behavioral therapy (CBT) produced greater decreases in depression at post-treament and greater decreases in fasting/2-h insulin at 1 year, compared to health education (HE). The current study is a secondary analysis of this parallel-group randomized controlled trial. We examined whether decreasing depression explained intervention effects on body composition and insulin outcomes. We hypothesized that decreases in depression would be an explanatory mediator and that indirect effects would be strongest at higher levels of baseline depression. Methods Participants were 12–17 years girls with overweight/obesity and family history of T2D randomized to 6-week group CBT (n = 58) or HE (n = 61). Procedures took place at an outpatient pediatric clinic. At baseline, post-treatment, and 1 year, adolescents completed the Center for Epidemiologic Studies-Depression Scale to assess depression symptoms; body mass index (BMI [kg/m2]) was measured from height/fasting weight; insulin resistance was derived from 2-h oral glucose testing. Adiposity was assessed with dual-energy X-ray absorptiometry at baseline and 1 year. Indirect effects of intervention were tested on 1-year changes in BMI, adiposity, and insulin through decreases in depression. Baseline depression was tested as a moderator of mediation. Results There was an indirect effect of CBT on decreased 1-year fasting insulin via decreases in depression during treatment, among adolescents with more elevated baseline depression. Conclusions Decreasing elevated depression may be one mechanism in the targeted prevention of T2D in at-risk adolescents.
Published: 2019
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21. Methodologic considerations for measuring energy expenditure differences between diets varying in carbohydrate using the doubly labeled water method

Author: Eric Ravussin, Rudolph Leibel, Marc L. Reitman, Kong Y. Chen, Kevin D. Hall, Smith, Michael Rosenbaum, and Juen Guo
Subjects: Adult, Male, 0301 basic medicine, Calorie, Physical Exertion, Energy balance, Medicine (miscellaneous), 030209 endocrinology & metabolism, Doubly labeled water, Body Mass Index, Diet, Carbohydrate-Restricted, 03 medical and health sciences, Absorptiometry, Photon, 0302 clinical medicine, Animal science, Accelerometry, Dietary Carbohydrates, Humans, Obesity, Exercise physiology, Letters to the Editor, Exercise, 030109 nutrition & dietetics, Nutrition and Dietetics, Chemistry, Respiration, Reproducibility of Results, Water, Calorimetry, Indirect, Feeding Behavior, Carbohydrate, Respiratory quotient, Original Research Communications, Energy expenditure, Research Design, Body Composition, Diet, Ketogenic, Energy Intake, Energy Metabolism, Body mass index
Abstract: BACKGROUND: Low-carbohydrate diets have been reported to significantly increase human energy expenditure when measured using doubly labeled water (DLW) but not by respiratory chambers. Although DLW may reveal true physiological differences undetected by respiratory chambers, an alternative possibility is that the expenditure differences resulted from failure to correctly estimate the respiratory quotient (RQ) used in the DLW calculations. OBJECTIVE: To examine energy expenditure differences between isocaloric diets varying widely in carbohydrate and to quantitatively compare DLW data with respiratory chamber and body composition measurements within an energy balance framework. DESIGN: DLW measurements were obtained during the final 2 wk of month-long baseline (BD; 50% carbohydrate, 35% fat, 15% protein) and isocaloric ketogenic diets (KD; 5% carbohydrate, 80% fat, 15% protein) in 17 men with a BMI of 25–35 kg/m(2). Subjects resided 2 d/wk in respiratory chambers to measure energy expenditure (EE(chamber)). DLW expenditure was calculated using chamber-determined RQ either unadjusted (EE(DLW)) or adjusted (EE(DLWΔRQ)) for net energy imbalance using diet-specific coefficients. Accelerometers measured physical activity. Body composition changes were measured by dual-energy X-ray absorptiometry (DXA) which were combined with energy intake measurements to calculate energy expenditure by balance (EE(bal)). RESULTS: After transitioning from BD to KD, neither EE(chamber) nor EE(bal) were significantly changed (∆EE(chamber )= 24 ± 30 kcal/d; P = 0.43 and ∆EE(bal )= −141 ± 118 kcal/d; P = 0.25). Similarly, physical activity (−5.1 ± 4.8%; P = 0.3) and exercise efficiency (−1.6 ± 2.4%; P = 0.52) were not significantly changed. However, EE(DLW) was 209 ± 83 kcal/d higher during the KD (P = 0.023) but was not significantly increased when adjusted for energy balance (EE(DLWΔRQ) = 139 ± 89 kcal/d; P = 0.14). After removing 2 outliers whose EE(DLW) were incompatible with other data, EE(DLW) was marginally increased during the KD by 126 ± 62 kcal/d (P = 0.063) and EE(DLW∆RQ) was only 46 ± 65 kcal/d higher (P = 0.49). CONCLUSIONS: DLW calculations failing to account for diet-specific energy imbalance effects on RQ erroneously suggest that low-carbohydrate diets substantially increase energy expenditure. This trial was registered at clinicaltrials.gov as NCT01967563.
Published: 2019
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22. Examining cognitive-behavioral therapy change mechanisms for decreasing depression, weight, and insulin resistance in adolescent girls at risk for type 2 diabetes

Author: Gulley, Lauren D., Shomaker, Lauren B., Kelly, Nichole R., Chen, Kong Y., Olsen, Cara H., Tanofsky-Kraff, Marian, and Yanovski, Jack A.
Subjects: Psychiatry and Mental health, Clinical Psychology, Adolescent, Cognitive Behavioral Therapy, Diabetes Mellitus, Type 2, Depression, Insulins, Humans, Female, Insulin Resistance, Article
Abstract: OBJECTIVE: Depression in adolescence is linked to risk for type 2 diabetes (T2D). In this secondary data analysis of a randomized controlled trial comparing cognitive-behavioral therapy (CBT) to a control program to ameliorate insulin resistance via reducing depression symptoms, we examine which CBT change mechanisms (e.g., behavioral activation, cognitive restructuring) contributed to decreased depression and subsequent improvements in body mass index (BMI), percent body fat, and insulin resistance. METHODS: Girls 12–17y with overweight/obesity and family history of T2D were randomized to six-week group CBT (n=61) or health education (HealthEd; n=58). At baseline and post-treatment, adolescents completed questionnaires assessing activities, thoughts, and depression symptoms. At baseline, post-treatment, and one- year, BMI was calculated and insulin outcomes were derived from two-hour oral glucose tolerance testing. At baseline and one-year, percent body fat was assessed with dual-energy x-ray absorptiometry. Indirect effects of CBT components were tested on one-year changes in BMI, percent body fat, and insulin indices through decreases in depression symptoms during treatment. Intervention was tested as a moderator. RESULTS: In CBT, but not HealthEd, there was an indirect effect of increased physical activity during treatment on decreased one-year BMI via reductions in depression symptoms during treatment. Also, there were conditional indirect effects in CBT of increased pleasantness of physical and social activity during treatment on decreased one-year BMI via decreased depression symptoms during treatment. CONCLUSION: Behavioral activation may be a useful intervention to decrease depression and reduce excess weight gain in the targeted prevention of T2D in at-risk adolescent girls. NCT01425905, clinicaltrials.gov
Published: 2022
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23. Retrieval-induced forgetting in children and adolescents with and without obesity

Author: Terry L. Davidson, Eliana Ramirez, Esther A. Kwarteng, Kweku G. Djan, Loie M. Faulkner, Megan N. Parker, Shanna B. Yang, Anna Zenno, Nichole R. Kelly, Lisa M. Shank, Marian Tanofsky-Kraff, Anastasia Snelling, Sarah Irvine Belson, Alexia Hyde, Kong Y. Chen, and Jack A. Yanovski
Subjects: Executive Function, Inhibition, Psychological, Pediatric Obesity, Nutrition and Dietetics, Adolescent, Endocrinology, Diabetes and Metabolism, Memory, Episodic, Mental Recall, Medicine (miscellaneous), Humans, Child
Abstract: Previous research indicates that youth with obesity exhibit deficits in executive functioning (EF), which often take the form of impaired response inhibition. One aspect of EF not previously studied in obesity is the adaptive process known as retrieval-induced forgetting (RIF), the suppression/inhibition of intrusive or non-target items by the retrieval of specific items from memory. The present study investigated if child or adolescent obesity disrupts the ability to inhibit retrieval of intrusive memories.We compared the manifestation of RIF in children (ages 8-12) and adolescents (ages 13-18) as a function of their weight status and sex. We also evaluated the effects of these variables on simple recall of items from episodic memory under conditions where competition from intrusive items was reduced.Children with obesity did not demonstrate significant RIF, whereas RIF was exhibited by preteens without obesity and by teenage participants with- and without obesity (Weight Status × Age Group interaction p = 0.028). This pattern of results did not differ as a function of sex for either age group. No differences in episodic memory were found. Additional analyses using Age as continuous covariate (and not as a nominal group) comparing participants who exhibited RIF with those who did not, found that the no RIF group consumed fast-food meals more frequently (p = 0.024) and had higher percentages of total body adiposity and android fat compared to the RIF group (p's 0.05).The findings expand what is known about the effects of childhood obesity on cognitive functioning, identify impaired RIF with specific behavioral and dietary factors and increased adiposity, and suggest the possibility that impairments in the ability to inhibit intrusive memories of food and eating may contribute to poor early-life weight control.
Published: 2021

24. Proton MR Spectroscopy Measurements of White and Brown Adipose Tissue in Healthy Humans: Relaxation Parameters and Unsaturated Fatty Acids

Author: Kong Y. Chen, Ahmed Hamimi, Zahraa Abdul Sater, Jatin R. Matta, Janet F. Eary, Ahmed M. Gharib, Ronald Ouwerkerk, Khaled Z. Abd-Elmoniem, and Aaron M. Cypess
Subjects: In vivo magnetic resonance spectroscopy, Adult, Male, Relaxometry, medicine.medical_specialty, Adipose Tissue, White, Proton Magnetic Resonance Spectroscopy, Adipose tissue, White adipose tissue, Sensitivity and Specificity, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Adipose Tissue, Brown, Fluorodeoxyglucose F18, Diabetes mellitus, Internal medicine, Positron Emission Tomography Computed Tomography, Brown adipose tissue, medicine, Lipolysis, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Aged, chemistry.chemical_classification, business.industry, Middle Aged, medicine.disease, Healthy Volunteers, medicine.anatomical_structure, Endocrinology, chemistry, 030220 oncology & carcinogenesis, Fatty Acids, Unsaturated, Female, Radiopharmaceuticals, business, Polyunsaturated fatty acid
Abstract: Background Activation of brown adipose tissue (BAT) in rodents increases lipolysis in white adipose tissue (WAT) and improves glucose tolerance. Adult humans can have metabolically active BAT. Implications for diabetes and obesity in humans require a better characterization of BAT in humans. Purpose To study fat depots with localized proton MR spectroscopy relaxometry and to identify differences between WAT and fluorine 18 fluorodeoxyglucose (FDG) PET/CT proven cold-activated BAT in humans. Materials and Methods Participants were consecutively enrolled in this prospective study (ClinicalTrials.gov identifiers: NCT01568671 and NCT01399385) from August 2016 to May 2019. Supraclavicular potential BAT regions were localized with MRI. Proton densities, T1, and T2 were measured with localized MR spectroscopy in potential BAT and in subcutaneous WAT. FDG PET/CT after cold stimulation was used to retrospectively identify active supraclavicular BAT or supraclavicular quiescent adipose tissue (QAT) regions. MR spectroscopy results from BAT and WAT were compared with grouped and paired tests. Results Of 21 healthy participants (mean age, 36 years ± 16 [standard deviation]; 13 men) FDG PET/CT showed active BAT in 24 MR spectroscopy-targeted regions in 16 participants (eight men). Four men had QAT. The T2 for methylene protons was shorter in BAT (mean, 69 msec ± 6, 24 regions) than in WAT (mean, 83 msec ± 3, 18 regions, P < .01) and QAT (mean, 78 msec ± 2, five regions, P < .01). A T2 cut-off value of 76 msec enabled the differentiation of BAT from WAT or QAT with a sensitivity of 85% and a specificity of 95%. Densities of protons adjacent and between double bonds were 33% and 24% lower, respectively, in BAT compared with those in WAT (P = .01 and P = .03, respectively), indicating a lower content of unsaturated and polyunsaturated fatty acids, respectively, in BAT compared with WAT. Conclusion Proton MR spectroscopy showed shorter T2 and lower unsaturated fatty acids in brown adipose tissue (BAT) than that in white adipose tissue in healthy humans. It was feasible to identify BAT with MR spectroscopy without the use of PET/CT or cold stimulation. © RSNA, 2021 See also the editorial by Barker in this issue. Online supplemental material is available for this article.
Published: 2021

25. How to Best Protect People With Diabetes From the Impact of SARS-CoV-2: Report of the International COVID-19 and Diabetes Summit

Author: Kong Y. Chen, Elias K. Spanakis, Bithika Thompson, David Ahn, Jennifer Y Zhang, Gerard L. Coté, David C. Klonoff, Trisha Shang, Lauren E. Wisk, Amisha Wallia, Juan Espinoza, Carlos E. Mendez, and David Kerr
Subjects: 2019-20 coronavirus outbreak, History, Coronavirus disease 2019 (COVID-19), 1918-1919, telehealth, Endocrinology, Diabetes and Metabolism, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), International Cooperation, Biomedical Engineering, digital health, 030209 endocrinology & metabolism, Bioengineering, Global Health, Diabetes Complications, 03 medical and health sciences, 0302 clinical medicine, Environmental health, Diabetes mellitus, Medical, Pandemic, Internal Medicine, Global health, medicine, Diabetes Mellitus, Humans, 030212 general & internal medicine, Influenza Pandemic, Pandemics, pandemic, COVID-19, diabetes, geography, Summit, geography.geographical_feature_category, Nutrition and Dietetics, Geography, Proceedings of Meetings/Conferences, Diabetes mellitus therapy, medicine.disease, Telemedicine, 20th Century, Societies
Abstract: The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has rapidly involved the entire world and exposed the pressing need for collaboration between public health and other stakeholders from the clinical, scientific, regulatory, pharmaceutical, and medical device and technology communities. To discuss how to best protect people with diabetes from serious outcomes from COVID-19, Diabetes Technology Society, in collaboration with Sansum Diabetes Research Institute, hosted the “International COVID-19 and Diabetes Virtual Summit” on August 26-27, 2020. This unique, unprecedented real-time conference brought together physicians, scientists, government officials, regulatory experts, industry representatives, and people with diabetes from six continents to review and analyze relationships between COVID-19 and diabetes. Over 800 attendees logged in. The summit consisted of five sessions: (I) Keynotes, (II) Preparedness, (III) Response, (IV) Recovery, and (V) Surveillance; eight parts: (A) Background, (B) Resilience, (C) Outpatient Care, (D) Inpatient Care, (E) Resources, (F) High-Risk Groups, (G) Regulation, and (H) The Future; and 24 sections: (1) Historic Pandemics and Impact on Society, (2) Pathophysiology/Risk Factors for COVID-19, (3) Social Determinants of COVID-19, (4) Preparing for the Future, (5) Medications and Vaccines, (6) Psychology of Patients and Caregivers, (7) Outpatient Treatment of Diabetes Mellitus and Non-Pharmacologic Intervention, (8) Technology and Telehealth for Diabetes Outpatients, (9) Technology for Inpatients, (10) Management of Diabetes Inpatients with COVID-19, (11) Ethics, (12) Accuracy of Diagnostic Tests, (13) Children, (14) Pregnancy, (15) Economics of Care for COVID-19, (16) Role of Industry, (17) Protection of Healthcare Workers, (18) People with Diabetes, (19) International Responses to COVID-19, (20) Government Policy, (21) Regulation of Tests and Treatments, (22) Digital Health Technology, (23) Big Data Statistics, and 24) Patient Surveillance and Privacy. The two keynote speeches were entitled (1) COVID-19 and Diabetes—Meeting the Challenge and (2) Knowledge Gaps and Research Opportunities for Diabetes and COVID-19. While there was an emphasis on diabetes and its interactions with COVID-19, the panelists also discussed the COVID-19 pandemic in general. The meeting generated many novel ideas for collaboration between experts in medicine, science, government, and industry to develop new technologies and disease treatment paradigms to fight this global pandemic.
Published: 2021

26. Response to 'Two Functional Calorimetric Chambers in France Complete the Room Indirect Calorimetry Operating and Reporting Guidelines (RICORS) 1.0 Guide List'

Author: Edward L. Melanson and Kong Y. Chen
Subjects: Nutrition and Dietetics, Endocrinology, Information retrieval, Computer science, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Humans, Calorimetry, Indirect, Calorimetry, France, Energy Metabolism
Published: 2021

27. Predicting Body Composition From Anthropometrics

Author: Kong Y. Chen
Subjects: Gerontology, Endocrinology, Diabetes and Metabolism, Biomedical Engineering, 030209 endocrinology & metabolism, Bioengineering, Body weight, Fat mass, Body Mass Index, Anthropometric parameters, 03 medical and health sciences, 0302 clinical medicine, Absorptiometry, Photon, Risk Factors, Diabetes mellitus, Internal Medicine, Medicine, Humans, 030212 general & internal medicine, Composition (language), Anthropometry, business.industry, Body Weight, Lean tissue, Original Articles, medicine.disease, Lean body mass, Body Composition, business
Abstract: Body weight, height, and other simple, noninvasive anthropometric measures are the cornerstones of epidemiological research. Body composition determinants such as fat and lean tissue masses and their distributions are better associated with metabolic conditions, such as diabetes, than anthropometrics alone. However, body composition is generally more challenging to measure. This analysis article comments on the manuscript by Cichosz et al that appeared in this issue of the Journal of Diabetes Science and Technology, where a machine-learning approach was developed to predict body composition using measured anthropometric parameters for potentially easier estimations of risk factors of metabolic diseases in the future.
Published: 2020

28. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

Author: Perkovic, V., Jardine, M. J., Neal, B., Bompoint, S., Heerspink, H. J. L., Charytan, D. M., Edwards, R., Agarwal, R., Bakris, G., Bull, S., Cannon, C. P., Capuano, G., Chu, P. -L., De Zeeuw, D., Greene, T., Levin, A., Pollock, C., Wheeler, D. C., Yavin, Y., Zhang, H., Zinman, B., Meininger, G., Brenner, B. M., Mahaffey, K. W., Perkovic, V, Mahaffey, Kw, Agarwal, R, Bakris, G, Brenner, Bm, Cannon, Cp, Charytan, Dm, de Zeeuw, D, Greene, T, Jardine, Mj, Heerspink, Hjl, Levin, A, Meininger, G, Neal, B, Pollock, C, Wheeler, Dc, Zhang, H, Zinman, B, Mcguire, Dk, Holman, R, Home, P, Scharfstein, D, Parfrey, P, Shahinfar, S, August, P, Chang, T, Sinha, Ad, Januzzi, J, Kolansky, D, Amerena, J, Hillis, G, Gorelick, P, Kissela, B, Kasner, S, Lindley, R, Fulcher, G, Ounadjela, S, Hufert, K, von Ingersleben, G, Gaglia, J, Harris, R, Hudson, M, Turchin, A, Cheifetz, A, Sheth, S, Feuerstein, J, Cohen, S, Jardine, M, Li, N, Kolesnyk, I, Aizenberg, D, Pecoits-Filho, R, Cherney, D 3rd, Obrador, G, Chertow, G, Hawley, C, Ji, L, Wada, T, Jha, V, Lim, Sk, Lim-Abrahan, Ma, Santos, F, Chae, Dw, Hwang, Sj, Vazelov, E, Rychlík, I, Hadjadj, S, Krane, V, Rosivall, L, De Nicola, L, Dreval, A, Nowicki, M, Schiller, A, Distiller, L, Górriz, Jl, Kolesnyk, M, Morren, F, Goykhman, S, David, C, Yost, L, Wang, H, Hettiarachchi, M, Thimmaiah, R, Koppolu, D, George, S, Schmidt, M, Ignjatovic, J, Chapin, L, Travis, K, Destree, M, Sood, V, Coffee, L, De Brouwer, K, Zaviriukha, V, Starzec, A, Koizumi, M, Lin, G, Chen, E, Lin, P, Leia, C, Mascaro, D, Amigo, A, Limos, A, Abrahamsen, I, Jaffer, S, Ahuad Guerrero RA, Albisu, Jp, Alvarisqueta, A, Bartolacci, I, Berli, Ma, Bordonava, A, Calella, P, Cantero, Mc, Cartasegna, Lr, Cercos, E, Coloma, Gc, Colombo, H, Commendatore, V, Cuadrado, J, Cuneo, Ca, Cusumano, Am, Douthat, Wg, Dran, Rd, Farias, E, Fernandez, Mf, Finkelstein, H, Fragale, G, Fretes, Jo, Garcia, Nh, Gastaldi, A, Gelersztein, E, Glenny, Ja, Gonzalez, Jp, Gonzalez Colaso PDC, Goycoa, C, Greloni, Gc, Guinsburg, A, Hermida, S, Juncos, Li, Klyver, Mi, Kraft, F, Krynski, F, Lanchiotti, Pv, Leon de la Fuente RA, Marchetta, N, Mele, P, Nicolai, S, Novoa, Pa, Orio, Si, Otreras, F, Oviedo, A, Raffaele, P, Resk, Jh, Rista, L, Rodriguez Papini, N, Sala, J, Santos, Jc, Schiavi, Lb, Sessa, H, Smith Casabella, T, Ulla, Mr, Valdez, M, Vallejos, A, Villarino, A, Visco, Ve, Wassermann, A, Zaidman, Cj, Cheung, Nw, Droste, C, Fraser, I, Johnson, D, Mah, Pm, Nicholls, K, Packham, D, Proietto, J, Roberts, A, Roger, S, Tsang, V, Raduan, Ra, Alves da Costa FA, Amodeo, C, Andreotti Turatti LA, Bregman, R, Camelo Sanches FC, Canani, Lh, Chacra, Ar, Cunha Borges JL, Cunha Vêncio SA, da Silva Franco RJ, D'Avila, D, de Souza Portes, E, de Souza, P, Deboni, Lm, Filho, Ff, Geloneze Neto, B, Gomes, M, Kohara, Sk, Keitel, E, Kerr Saraiva JF, Kurtz Lisboa HR, de Carvalho Contieri FL, Milagres, R, Montenegro Junior, R, Moreira de Brito, C, Nazzer Hissa, M, Nazario Sabbag ÂR, Noronha, I, Panarotto, D, Pecoits Filho, R, Pereira, Ma, Saporito, W, Scotton, As, Schuch, T, Simões de Almeida, R, Slompo Ramos, C, Soares Felício, J, Thomé, F, Tibes Hachmann JC, Yamada, S, Yoiti Hayashida, C, Zanata Petry TB, Zanella, Mt, Andreeva, V, Angelova, A, Dimitrov, S, Genadieva, V, Genova-Hristova, G, Hristozov, K, Kamenov, Z, Koundurdjiev, A, Lozanov, L, Margaritov, V, Nonchev, B, Rangelov, R, Shinkov, A, Temelkova, M, Velichkova, E, Yakov, A, Aggarwal, N, Aronson, R, Bajaj, H, Chouinard, G, Conway, J, Cournoyer, S, Daroza, G, De Serres, S, Dubé, F, Goldenberg, R, Gupta, A, Gupta, M, Henein, S, Khandwala, H, Leiter, L, Madore, F, Mcmahon, A, Muirhead, N, Pichette, V, Rabasa-Lhoret, R, Steele, A, Tangri, N, Torshizi, A, Woo, V, Zalunardo, N, Fernández Montenegro MA, Godoy Jorquera JG, Medina Fariña, M, Saavedra Gajardo, V, Vejar, M, Chen, N, Chen, Q, Gan, S, Kong, Y, Li, D, Li, W, Li, X, Lin, H, Liu, J, Lu, W, Mao, H, Ren, Y, Song, W, Sun, J, Sun, L, Tu, P, Wang, G, Yang, J, Yin, A, Yu, X, Zhao, M, Zheng, H, Accini Mendoza JL, Arcos, E, Avendano, J, Diaz Ruiz JEA, Garcia Ortiz LH, Gonzalez, A, Hernandez Triana, E, Higuera, Jd, Malaver, N, Molina de Salazar DI, Rosero, R, Terront Lozano MA, Valderrama Cometa, L, Valenzuela, A, Vargas Alonso RD, Villegas, I, Yupanqui, H, Bartaskova, D, Barton, P, Belobradkova, J, Dohnalova, L, Drasnar, T, Ferkl, R, Halciakova, K, Klokocnikova, V, Kovar, R, Lastuvka, J, Lukac, M, Pesickova, S, Peterka, K, Pumprla, J, Rychlik, I, Saudek, F, Tesar, V, Valis, M, Weiner, P, Zemek, S, Alamartine, E, Borot, S, Cariou, B, Dussol, B, Fauvel, Jp, Gourdy, P, Klein, A, Le Meur, Y, Penfornis, A, Roussel, R, Saulnier, Pj, Thervet, E, Zaoui, P, Burst, V, Faghih, M, Faulmann, G, Haller, H, Jerwan-Keim, R, Maxeiner, S, Paschen, B, Plassmann, G, Rose, L, Gonzalez Orellana RA, Haase, Fp, Moreira Diaz JP, Ramirez Roca LA, Sánchez Arenales JA, Sanchez Polo JV, Turcios Juarez, E, Csecsei, G, Csiky, B, Danos, P, Deak, L, Dudas, M, Harcsa, E, Keltai, K, Keresztesi, S, Kiss, K, Konyves, L, Major, L, Mileder, M, Molnar, M, Mucsi, J, Oroszlan, T, Ory, I, Paragh, G, Peterfai, E, Petro, G, Revesz, K, Takacs, R, Vangel, S, Vasas, S, Zsom, M, Abraham, O, Bhushan, Rs, Deepak, D, Edwin, Fm, Gopalakrishnan, N, Gracious, N, Hansraj, A, Jain, D, Keshavamurthy, Cb, Khullar, D, Manisha, S, Peringat, J, Prasad, N, Satyanarayana, Rk, Sreedhar, R, Sreelatha, M, Sudhakar, B, Vyasam, Rc, Bonadonna, R, Castellino, P, Ceriello, A, Chiovato, L, De Cosmo, S, Derosa, G, Di Carlo, A, Di Cianni, G, Frascà, G, Fuiano, G, Gambaro, G, Garibotto, G, Giorda, C, Malberti, F, Mandreoli, M, Mannucci, E, Orsi, E, Piatti, P, Santoro, D, Sasso, Fc, Serviddio, G, Stella, A, Trevisan, R, Veronelli, Am, Zanoli, L, Akiyama, H, Aoki, H, Asano, A, Iitsuka, T, Kajiyama, S, Kashine, S, Kawada, T, Kodera, T, Kono, H, Koyama, K, Kumeda, Y, Miyauchi, S, Mizuyama, K, Niiya, T, Oishi, H, Ota, S, Sakakibara, T, Takai, M, Tomonaga, O, Tsujimoto, M, Wakasugi, M, Wakida, Y, Watanabe, T, Yamada, M, Yanagida, K, Yanase, T, Yumita, W, Gaupsiene, E, Kozloviene, D, Navickas, A, Urbanaviciene, E, Abdul Ghani, R, Abdul Kadir, K, Ali, N, Che Yusof MD, Gan, Cl, Ismail, M, Kong, Wy, Lam, Sw, Lee, Ly, Loh, Cl, Manocha, Ab, Ng, Ks, Nik Ahmad NNF, Ratnasingam, V, Bin Shudim SS, Vengadasalam, P, Abraira Munoz LD, Salazar, Ma, Cruz, Jb, Soto, Mb, Ramos, Jc, Wong, Ac, Correa Rotter JR, Diaz Escalante, T, Enriquez Sosa FE, Flores Lozano, F, Flota Cervera LF, Frenk Baron, P, Garcia Ballesteros, C, Gomez Rangel JD, Herrera Jimenez LE, Irizar Santana SS, Jimenez Florez, F, Laviada Molina, H, Luna Ceballos RI, Martin Del Camp Blanco, B, Morales Franco, G, Moreno Loza OT, Mustieles Rocha, C, Obrador Vera, G, Orozco Castellanos, R, Peralta Calcaneo, J, Reyes Rosano MA, Rodriguez Pattzi, H, Rosas Guzman, J, Rucker Joerg IE, Saaveddra Sanchez SB, Sanchez Mijangos JH, Serrano Sanson, P, Tamayo, Y Orozco JA, Tellez Chavez, E, Valdes Depeda, A, Venegas Carrillo, L, Villagordoa Mesa, J, Zamarripa Escobedo, R, Baker, J, Noonan, P, Scott, R, Walker, R, Watson, E, Williams, M, Young, S, Abejuela, Z, Agra, J, Aquitania, G, Caringal, C, Comia, Rs, Delos Santos, L, Gomez, O, Jimeno, C, Tan, G, Tolentino, M, Yao, C, Yap, Ye, Ygpuara, Mdl, Bijata-Bronisz, R, Hotlos, L, Januszewicz, A, Kaczmarek, B, Kaminska, A, Lazuka, L, Madej, A, Mazur, S, Mlodawska-Choluj, D, Orlowska-Kowalik, G, Popenda, G, Rewerska, B, Sowinski, D, Angelescu, Lm, Anghel, V, Avram, Ri, Busegeanu, Mm, Cif, A, Cosma, D, Crisan, C, Demian, Ld, Ferariu, Ie, Halmagyi, I, Hancu, N, Munteanu, M, Negru, D, Onaca, Ag, Petrica, L, Popa, Ar, Ranetti, Ae, Serafinceanu, C, Toarba, C, Agafyina, A, Barbarash, O, Barysheva, O, Chizhov, D, Dobronravov, V, Glinkina, I, Grineva, E, Khirmanov, V, Kolmakova, E, Koroleva, T, Kvitkova, L, Marasaev, V, Mkrtumyan, A, Morugova, T, Nagibovich, G, Nagibovich, O, Nedogoda, S, Osipova, I, Raskina, T, Samoylova, Y, Sazonova, O, Shamkhalova, M, Shutemova, E, Shwartz, Y, Uriasyev, O, Vorobyev, S, Zateyshchikova, A, Zateyshshikov, D, Zykova, T, Antic, S, Djordjevic, M, Kendereski, A, Lalic, K, Lalic, N, Popovic-Radinovic, V, Babikova, J, Benusova, O, Buganova, I, Culak, J, Dzupina, A, Dzuponova, J, Fulop, P, Ilavska, A, Martinka, E, Ochodnicka, Z, Pella, D, Smatanova, I, Ahmed, F, Badat, A, Breedt, J, Govender, V, Govender, R, 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Heerspink, Hiddo J L, Charytan, David M, Edwards, Robert, Agarwal, Rajiv, Bakris, George, Bull, Scott, Cannon, Christopher P, Capuano, George, Chu, Pei-Ling, de Zeeuw, Dick, Greene, Tom, Levin, Adeera, Pollock, Carol, Wheeler, David C, Yavin, Yshai, Zhang, Hong, Zinman, Bernard, Meininger, Gary, Brenner, Barry M, Mahaffey, Kenneth W, collaborator: Perkovic, V, Mahaffey, Kw, Agarwal, R, Bakris, G, Brenner, Bm, Cannon, Cp, Charytan, Dm, de Zeeuw, D, Greene, T, Jardine, Mj, Heerspink, Hjl, Levin, A, Meininger, G, Neal, B, Pollock, C, Wheeler, Dc, Zhang, H, Zinman, B, Mcguire, Dk, Holman, R, Home, P, Scharfstein, D, Parfrey, P, Shahinfar, S, August, P, Chang, T, Sinha, Ad, Januzzi, J, Kolansky, D, Amerena, J, Hillis, G, Gorelick, P, Kissela, B, Kasner, S, Lindley, R, Fulcher, G, Ounadjela, S, Hufert, K, von Ingersleben, G, Gaglia, J, Harris, R, Hudson, M, Turchin, A, Cheifetz, A, Sheth, S, Feuerstein, J, Cohen, S, Jardine, M, Li, N, Kolesnyk, I, Aizenberg, D, Pecoits-Filho, R, Cherney, D 3rd, Obrador, G, Chertow, G, Hawley, C, Ji, L, Wada, T, Jha, V, Lim, Sk, Lim-Abrahan, Ma, Santos, F, Chae, Dw, Hwang, Sj, Vazelov, E, Rychlík, I, Hadjadj, S, Krane, V, Rosivall, L, De Nicola, L, Dreval, A, Nowicki, M, Schiller, A, Distiller, L, Górriz, Jl, Kolesnyk, M, Morren, F, Goykhman, S, David, C, Yost, L, Wang, H, Hettiarachchi, M, Thimmaiah, R, Koppolu, D, George, S, Schmidt, M, Ignjatovic, J, Chapin, L, Travis, K, Destree, M, Sood, V, Coffee, L, De Brouwer, K, Zaviriukha, V, Starzec, A, Koizumi, M, Lin, G, Chen, E, Lin, P, Leia, C, Mascaro, D, Amigo, A, Limos, A, Abrahamsen, I, Jaffer, S, Ahuad Guerrero, Ra, Albisu, Jp, Alvarisqueta, A, Bartolacci, I, Berli, Ma, Bordonava, A, Calella, P, Cantero, Mc, Cartasegna, Lr, Cercos, E, Coloma, Gc, Colombo, H, Commendatore, V, Cuadrado, J, Cuneo, Ca, Cusumano, Am, Douthat, Wg, Dran, Rd, Farias, E, Fernandez, Mf, Finkelstein, H, Fragale, G, Fretes, Jo, Garcia, Nh, Gastaldi, A, Gelersztein, E, Glenny, Ja, Gonzalez, Jp, Gonzalez Colaso, Pdc, Goycoa, C, Greloni, Gc, Guinsburg, A, Hermida, S, Juncos, Li, Klyver, Mi, Kraft, F, Krynski, F, Lanchiotti, Pv, Leon de la Fuente, Ra, Marchetta, N, Mele, P, Nicolai, S, Novoa, Pa, Orio, Si, Otreras, F, Oviedo, A, Raffaele, P, Resk, Jh, Rista, L, Rodriguez Papini, N, Sala, J, Santos, Jc, Schiavi, Lb, Sessa, H, Smith Casabella, T, Ulla, Mr, Valdez, M, Vallejos, A, Villarino, A, Visco, Ve, Wassermann, A, Zaidman, Cj, Cheung, Nw, Droste, C, Fraser, I, Johnson, D, Mah, Pm, Nicholls, K, Packham, D, Proietto, J, Roberts, A, Roger, S, Tsang, V, Raduan, Ra, Alves da Costa, Fa, Amodeo, C, Andreotti Turatti, La, Bregman, R, Camelo Sanches, Fc, Canani, Lh, Chacra, Ar, Cunha Borges, Jl, Cunha Vêncio, Sa, da Silva Franco, Rj, D'Avila, D, de Souza Portes, E, de Souza, P, Deboni, Lm, Filho, Ff, Geloneze Neto, B, Gomes, M, Kohara, Sk, Keitel, E, Kerr Saraiva, Jf, Kurtz Lisboa, Hr, de Carvalho Contieri, Fl, Milagres, R, Montenegro Junior, R, Moreira de Brito, C, Nazzer Hissa, M, Nazario Sabbag, Âr, Noronha, I, Panarotto, D, Pecoits Filho, R, Pereira, Ma, Saporito, W, Scotton, A, Schuch, T, Simões de Almeida, R, Slompo Ramos, C, Soares Felício, J, Thomé, F, Tibes Hachmann, Jc, Yamada, S, Yoiti Hayashida, C, Zanata Petry, Tb, Zanella, Mt, Andreeva, V, Angelova, A, Dimitrov, S, Genadieva, V, Genova-Hristova, G, Hristozov, K, Kamenov, Z, Koundurdjiev, A, Lozanov, L, Margaritov, V, Nonchev, B, Rangelov, R, Shinkov, A, Temelkova, M, Velichkova, E, Yakov, A, Aggarwal, N, Aronson, R, Bajaj, H, Chouinard, G, Conway, J, Cournoyer, S, Daroza, G, De Serres, S, Dubé, F, Goldenberg, R, Gupta, A, Gupta, M, Henein, S, Khandwala, H, Leiter, L, Madore, F, Mcmahon, A, Muirhead, N, Pichette, V, Rabasa-Lhoret, R, Steele, A, Tangri, N, Torshizi, A, Woo, V, Zalunardo, N, Fernández Montenegro, Ma, Godoy Jorquera, Jg, Medina Fariña, M, Saavedra Gajardo, V, Vejar, M, Chen, N, Chen, Q, Gan, S, Kong, Y, Li, D, Li, W, Li, X, Lin, H, Liu, J, Lu, W, Mao, H, Ren, Y, Song, W, Sun, J, Sun, L, Tu, P, Wang, G, Yang, J, Yin, A, Yu, X, Zhao, M, Zheng, H, Accini Mendoza, Jl, Arcos, E, Avendano, J, Diaz Ruiz, Jea, Garcia Ortiz, Lh, Gonzalez, A, Hernandez Triana, E, Higuera, Jd, Malaver, N, Molina de Salazar, Di, Rosero, R, Terront Lozano, Ma, Valderrama Cometa, L, Valenzuela, A, Vargas Alonso, Rd, Villegas, I, Yupanqui, H, Bartaskova, D, Barton, P, Belobradkova, J, Dohnalova, L, Drasnar, T, Ferkl, R, Halciakova, K, Klokocnikova, V, Kovar, R, Lastuvka, J, Lukac, M, Pesickova, S, Peterka, K, Pumprla, J, Rychlik, I, Saudek, F, Tesar, V, Valis, M, Weiner, P, Zemek, S, Alamartine, E, Borot, S, Cariou, B, Dussol, B, Fauvel, Jp, Gourdy, P, Klein, A, Le Meur, Y, Penfornis, A, Roussel, R, Saulnier, Pj, Thervet, E, Zaoui, P, Burst, V, Faghih, M, Faulmann, G, Haller, H, Jerwan-Keim, R, Maxeiner, S, Paschen, B, Plassmann, G, Rose, L, Gonzalez Orellana, Ra, Haase, Fp, Moreira Diaz, Jp, Ramirez Roca, La, Sánchez Arenales, Ja, Sanchez Polo, Jv, Turcios Juarez, E, Csecsei, G, Csiky, B, Danos, P, Deak, L, Dudas, M, Harcsa, E, Keltai, K, Keresztesi, S, Kiss, K, Konyves, L, Major, L, Mileder, M, Molnar, M, Mucsi, J, Oroszlan, T, Ory, I, Paragh, G, Peterfai, E, Petro, G, Revesz, K, Takacs, R, Vangel, S, Vasas, S, Zsom, M, Abraham, O, Bhushan, R, Deepak, D, Edwin, Fm, Gopalakrishnan, N, Gracious, N, Hansraj, A, Jain, D, Keshavamurthy, Cb, Khullar, D, Manisha, S, Peringat, J, Prasad, N, Satyanarayana, Rk, Sreedhar, R, Sreelatha, M, Sudhakar, B, Vyasam, Rc, Bonadonna, R, Castellino, P, Ceriello, A, Chiovato, L, De Cosmo, S, Derosa, G, Di Carlo, A, Di Cianni, G, Frascà, G, Fuiano, G, Gambaro, G, Garibotto, G, Giorda, C, Malberti, F, Mandreoli, M, Mannucci, E, Orsi, E, Piatti, P, Santoro, D, Sasso, Fc, Serviddio, G, Stella, A, Trevisan, R, Veronelli, Am, Zanoli, L, Akiyama, H, Aoki, H, Asano, A, Iitsuka, T et al, Groningen Kidney Center (GKC), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
Subjects: Aged, Canagliflozin, Cardiovascular Diseases, Creatinine, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Double-Blind Method, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic, Male, Middle Aged, Sodium-Glucose Transporter 2 Inhibitors, Type 2 diabetes, 030204 cardiovascular system & hematology, Diabetic nephropathy, Kidney Failure, chemistry.chemical_compound, 0302 clinical medicine, 030212 general & internal medicine, 03.02. Klinikai orvostan, Dapagliflozin, Chronic, 11 Medical and Health Sciences, EMPAGLIFLOZIN, General Medicine, Life Sciences & Biomedicine, Type 2, medicine.drug, medicine.medical_specialty, Nephropathy, 03 medical and health sciences, Medicine, General & Internal, Internal medicine, Diabetes mellitus, General & Internal Medicine, CREDENCE Trial Investigators, medicine, Diabetes Mellitus, Science & Technology, business.industry, urogenital system, diabetic nephropathy, Type 2 Diabetes Mellitus, KIDNEY-DISEASE, medicine.disease, chemistry, business, Kidney disease
Abstract: BACKGROUND: Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium-glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS: In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin-angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of
Published: 2019

29. Reduced brown adipose tissue activity during cold exposure is a metabolic feature of the human thrifty phenotype

Author: Alessio Basolo, Tim Hollstein, Karyne Lima Vinales, Aaron M. Cypess, Mathias Schlögl, Kong Y. Chen, Paolo Piaggi, Jonathan Krakoff, University of Zurich, and Piaggi, Paolo
Subjects: 0301 basic medicine, Male, 11221 Clinic for Geriatric Medicine, Endocrinology, Diabetes and Metabolism, Cold exposure, Brown adipose tissue, 0302 clinical medicine, Endocrinology, Adipose Tissue, Brown, A determinant, Thrifty phenotype, integumentary system, Thermogenesis, Fasting, Middle Aged, Metabolic phenotype, 1310 Endocrinology, Diabetes and Metabolism, Energy expenditure, Obesity, Cold Temperature, 2712 Endocrinology, Diabetes and Metabolism, medicine.anatomical_structure, Phenotype, Body Composition, Female, medicine.symptom, Adult, medicine.medical_specialty, Adolescent, 030209 endocrinology & metabolism, 610 Medicine & health, Article, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, business.industry, Calorimetry, Indirect, medicine.disease, 030104 developmental biology, business, Energy Metabolism, Weight gain
Abstract: Background We recently demonstrated that thrifty subjects, characterized by a greater decrease in 24 h energy expenditure (24hEE) during short-term fasting, have less capacity for cold-induced thermogenesis (CIT) during 24 h of mild cold exposure. Objective As cold-induced brown adipose tissue activation (CIBA) is a determinant of CIT, we sought to investigate whether thrifty individuals also have reduced CIBA. Methods Twenty-four healthy subjects (age: 29.8 ± 9.5y, body fat: 27.3 ± 12.4%, 63% male) were admitted to our clinical research unit and underwent two 24hEE assessments in a whole-room indirect calorimeter during energy balance and fasting conditions at thermoneutrality to quantify their degree of thriftiness. Positron emission tomography/computed tomography scans were performed after exposure to 16 °C for 2 h to quantify peak CIBA. Results A greater decrease in 24hEE during fasting was associated with lower peak CIBA (r = 0.50, p = 0.01), such that a 100 kcal/day greater reduction in 24hEE related to an average 3.2 g/mL lower peak CIBA. Conclusion Our results indicate that reduced CIBA is a metabolic trait of the thrifty phenotype which might explain reduced CIT capacity and greater predisposition towards weight gain in individuals with a thrifty metabolism.
Published: 2020

30. Association between free-living sleep and memory and attention in healthy adolescents

Author: Alexander Lundervold, Hilde Gundersen, Sigridur Gudmundsdottir, Vaka Rognvaldsdottir, Kong Y. Chen, Sunna Gestsdottir, Erlingur Johannsson, Runa Stefansdottir, and Robert J. Brychta
Subjects: Male, medicine.medical_specialty, Adolescent, Science, Psychology, Adolescent, Audiology, Neuropsychological Tests, Article, Task (project management), 03 medical and health sciences, 0302 clinical medicine, Cognition, medicine, Sleep and memory, Humans, Attention, Short-term memory, 030212 general & internal medicine, Effects of sleep deprivation on cognitive performance, Sleep restriction, Multidisciplinary, Working memory, Sleep in non-human animals, Healthy Volunteers, Cognitive test, Sleep deprivation, Memory, Short-Term, Visual Perception, Medicine, Female, Psychology, Sleep, 030217 neurology & neurosurgery, Psychomotor Performance
Abstract: In laboratory studies, imposed sleep restriction consistently reduces cognitive performance. However, the association between objectively measured, free-living sleep and cognitive function has not been studied in older adolescents. To address this gap, we measured one week of sleep with a wrist-worn GT3X+ actigraph in 160 adolescents (96 girls, 17.7 ± 0.3 years) followed by assessment of working memory with an n-back task and visual attention with a Posner cue-target task. Over the week, participants spent 7.1 ± 0.8 h/night in bed and slept 6.2 ± 0.8 h/night with 88.5 ± 4.8% efficiency and considerable intra-participant night-to-night variation, with a standard deviation in sleep duration of 1.2 ± 0.7 h. Sleep measures the night before cognitive testing were similar to weekly averages. Time in bed the night before cognitive testing was negatively associated with response times during the most challenging memory task (3-back; p = 0.005). However, sleep measures the night before did not correlate with performance on the attention task and weekly sleep parameters were not associated with either cognitive task. Our data suggests shorter acute free-living sleep may negatively impact difficult memory tasks, however the relationship between free-living sleep and cognitive task performance in healthy adolescents is less clear than that of laboratory findings, perhaps due to high night-to-night sleep variation.
Published: 2020

31. Human performance research for military operations in extreme cold environments

Author: Boris Kingma, Svein Martini, Emilie Gautier-Wong, Kong Y. Chen, François Haman, Karl E. Friedl, and Wendy Sullivan-Kwantes
Subjects: education, Poison control, Physical Therapy, Sports Therapy and Rehabilitation, Occupational safety and health, Extreme Cold Weather, 03 medical and health sciences, 0302 clinical medicine, Aeronautics, Cold acclimation, Humans, Orthopedics and Sports Medicine, 030212 general & internal medicine, Military Medicine, Extreme Cold, Personal Protective Equipment, Human factors and ergonomics, Thermogenesis, 030229 sport sciences, Equipment Design, Military Health, Field monitoring, The arctic, Military personnel, Military Personnel, Research Design, Psychology
Abstract: Objectives Soldier performance in the Arctic depends on planning and training, protective equipment, and human physiological limits. The purpose of this review was to highlight the span of current research on enhancing soldier effectiveness in extreme cold and austere environments. Methods The practices of seasoned soldiers who train in the Arctic and cold-dwelling natives inform performance strategies. We provide examples of research and technology that build on these concepts. Results Examples of current performance research include evaluation of equipment and tactics such as the bioenergetics of load carriage over snow in Norwegian exercises; Canadian field monitoring of hand temperatures and freezing cold injuries for better protection of manual dexterity; and Dutch predictive modeling of cold-wet work tolerances. Healthy young men can respond to cold with a substantial thermogenic response based on US and Canadian studies on brown adipose tissue and other mechanisms of non-shivering thermogenesis; the potential advantage of greater fat insulation is offset in obese unfit subjects by a smaller thermogenic response. Current physiological studies are addressing previously unanswered problems of cold acclimation procedures, thermogenic enhancement and regulation, and modulation of sympathetic activation, all of which may further enhance cold survival and expand the performance envelope. Conclusion There is an inseparable behavioral component to soldier performance in the Arctic, and even the best equipment does not benefit soldiers who have not trained in the actual environment. Training inexperienced soldiers to performance limits may be helped with personal monitoring technologies and predictive models.
Published: 2020

32. Room Indirect Calorimetry Operating and Reporting Standards (RICORS 1.0): A Guide to Conducting and Reporting Human Whole-Room Calorimeter Studies

Author: Guy Plasqui, Robert J. Brychta, Peter R. Murgatroyd, Shigeho Tanaka, Eric Ravussin, Edward L. Melanson, Steve Smith, Corey A. Rynders, Jonathan Krakoff, Paul F.M. Schoffelen, Elvis A. Carnero, Kong Y. Chen, Yoichi Hatamoto, and Christopher Bock
Subjects: 2019-20 coronavirus outbreak, SLEEPING METABOLIC-RATE, Computer science, Endocrinology, Diabetes and Metabolism, BODY INDIRECT CALORIMETER, Energy metabolism, Medicine (miscellaneous), Human metabolism, 24-H ENERGY-EXPENDITURE, 030209 endocrinology & metabolism, EXERCISE, Calorimetry, DETERMINANTS, OXIDATION, Article, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Consistency (negotiation), Humans, 030212 general & internal medicine, SPONTANEOUS PHYSICAL-ACTIVITY, Nutrition and Dietetics, Calorimetry, Indirect, Reference Standards, Calorimeter, Technical performance, Energy expenditure, Risk analysis (engineering), INTRAINDIVIDUAL VARIABILITY, GASEOUS EXCHANGE, Energy Metabolism, RESPIRATION CHAMBER
Abstract: Whole-room indirect calorimeters have been used to study human metabolism for more than a century. These studies have contributed substantial knowledge to the assessment of nutritional needs and the regulation of energy expenditure and substrate oxidation in humans. However, comparing results from studies conducted at different sites is challenging because of a lack of consistency in reporting technical performance, study design, and results. In May 2019, an expert panel was convened to consider minimal requirements for conducting and reporting the results of human whole-room indirect calorimeter studies. We propose Room Indirect Calorimetry Operating and Reporting Standards, version 1.0 (RICORS 1.0) to provide guidance to ensure consistency and facilitate meaningful comparisons of human energy metabolism studies across publications, laboratories, and clinical sites.
Published: 2020

33. Is activation of human brown adipose tissue a viable target for weight management?

Author: Eric Ravussin, Kong Y. Chen, and Kara L. Marlatt
Subjects: 0301 basic medicine, medicine.medical_specialty, animal structures, Physiology, Energy balance, Biology, Body weight, 03 medical and health sciences, Adipose Tissue, Brown, Hypothermia, Induced, Weight loss, Physiology (medical), Internal medicine, Weight Loss, Brown adipose tissue, Weight management, medicine, Animals, Humans, Obesity, Human studies, Treatment Outcome, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Energy expenditure, Anti-Obesity Agents, Insulin Resistance, medicine.symptom, Energy Metabolism, Thermogenesis, Perspectives
Abstract: To date, human studies show that brown adipose tissue (BAT) contributes a small yet highly variable amount to overall energy expenditure. No studies have shown a decrease in body weight with cold-induced BAT activation, and existing pharmacological studies suggest that BAT activation via the sympathetic nervous system may result in increased heart rate and systolic blood pressure. Furthermore, even though the amount and/or activity of BAT have been shown to vary with seasons, such variation does not seem to be translated into weight changes. Collectively, these findings do not support the use of BAT activation for weight loss in humans; however, the potential role of BAT in counteracting the metabolic adaptation observed with weight loss is suggested. Although the role of BAT in weight control is currently unsubstantiated, BAT may play a role in improving insulin sensitivity in humans.
Published: 2018
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34. Exercise modulates the interaction between cognition and anxiety in humans

Author: Abigail Hsiung, Tiffany R. Lago, Monique Ernst, Kong Y. Chen, Christian Grillon, Courtney J. Duckworth, Brooks P. Leitner, and Nicholas L. Balderston
Subjects: Adult, Male, medicine.drug_class, Experimental and Cognitive Psychology, Anxiety, Anxiolytic, Article, 050105 experimental psychology, 03 medical and health sciences, Cognition, 0302 clinical medicine, Arts and Humanities (miscellaneous), Heart Rate, Developmental and Educational Psychology, medicine, Humans, Attention, 0501 psychology and cognitive sciences, Exercise, Working memory, Mechanism (biology), 05 social sciences, Attentional control, Healthy Volunteers, Memory, Short-Term, Female, medicine.symptom, Psychology, 030217 neurology & neurosurgery, Cognitive psychology
Abstract: Despite interest in exercise as a treatment for anxiety disorders the mechanism behind the anxiolytic effects of exercise is unclear. Two observations motivate the present work. First, engagement of attention control during increased working memory (WM) load can decrease anxiety. Second, exercise can improve attention control. Therefore, exercise could boost the anxiolytic effects of increased WM load via its strengthening of attention control. Anxiety was induced by threat of shock and was quantified with anxiety-potentiated startle (APS). Thirty-five healthy volunteers (19 male, age M = 26.11, SD = 5.52) participated in two types of activity, exercise (biking at 60-70% of heart rate reserve) and control-activity (biking at 10-20% of heart rate reserve). After each activity, participants completed a WM task (n-back) at low- and high-load during safe and threat. Results were not consistent with the hypothesis: exercise vs. control-activity increased APS in high-load (p = .03). However, this increased APS was not accompanied with threat-induced impairment in WM performance (p = .37). Facilitation of both task-relevant stimulus processing and task-irrelevant threat processing, concurrent with prevention of threat interference on cognition, suggests that exercise increases cognitive ability. Future studies should explore how exercise affects the interplay of cognition and anxiety in patients with anxiety disorders.
Published: 2018
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35. Comparing ActiGraph equations for estimating energy expenditure in older adults

Author: Robert J. Brychta, Nicolas Aguilar-Farias, Geeske Peeters, Wendy J. Brown, and Kong Y. Chen
Subjects: Male, Accurate estimation, Physical activity, Physical Therapy, Sports Therapy and Rehabilitation, Fitness Trackers, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, 0302 clinical medicine, Activities of Daily Living, Statistics, Humans, Orthopedics and Sports Medicine, Exercise, Motion sensors, Aged, Mathematics, Aged, 80 and over, Age Factors, Reproducibility of Results, Calorimetry, Indirect, 030229 sport sciences, Actigraphy, Energy expenditure, Female, Sedentary Behavior, Energy Metabolism
Abstract: Accurate estimation of energy expenditure (EE) from accelerometer outputs remains a challenge in older adults. The aim of this study was to validate different ActiGraph (AG) equations for predicting EE in older adults. Forty older adults (age = 77.4 ± 8.1 yrs) completed a set of household/gardening activities in their residence, while wearing an AG at the hip (GT3X+) and a portable calorimeter (MetaMax 3B - criterion). Predicted EEs from AG were calculated using five equations (Freedson, refined Crouter, Sasaki and Santos-Lozano (vertical-axis, vectormagnitude)). Accuracy of equations was assessed using root-mean-square error (RMSE) and mean bias. The Sasaki equation showed the lowest RMSE for all activities (0.47 METs) and across physical activity intensities (PAIs) (range 0.18-0.48 METs). The Freedson and Santos-Lozano equations tended to overestimate EE for sedentary activities (range: 0.48 to 0.97 METs), while EEs for moderate-to-vigorous activities (MVPA) were underestimated (range: -1.02 to -0.64 METs). The refined Crouter and Sasaki equations showed no systematic bias, but they respectively overestimated and underestimated EE across PAIs. In conclusion, none of the equations was completely accurate for predicting EE across the range of PAIs. However, the refined Crouter and Sasaki equations showed better overall accuracy and precision when compared with the other methods.
Published: 2018
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36. Exercise decreases defensive responses to unpredictable, but not predictable, threat

Author: Christian Grillon, Kong Y. Chen, Brooks P. Leitner, Monique Ernst, Abigail Hsiung, Tiffany R. Lago, and Courtney J. Duckworth
Subjects: Adult, Male, Reflex, Startle, medicine.medical_specialty, medicine.drug_class, Anxiety, Anxiolytic, Article, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Healthy volunteers, Humans, Medicine, Exercise, business.industry, Fear, Anticipation, Psychological, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Sustained response, Female, medicine.symptom, business, Heart rate reserve, 030217 neurology & neurosurgery, Startle potentiation
Abstract: Background Research supports the anxiolytic effect of exercise, but the mechanism underlying this effect is unclear. This study examines the influence of exercise in healthy controls on two distinct defensive states implicated in anxiety disorders: fear, a phasic response to a predictable threat, and anxiety, a sustained response to an unpredictable threat. Methods Thirty-four healthy volunteers (17 male, age M = 26.18, SD = 5.6) participated in sessions of exercise (biking at 60-70% of heart rate reserve) and control (biking at 10-20% of heart rate reserve) activity for 30 min, separated by 1 week. Threat responses were measured by eyeblink startle and assessed with the "Neutral-Predictable-Unpredictable threat test," which includes a neutral (N) and two threat conditions, one with predictable (P) and one with unpredictable (U) shock. Results Results show that exercise versus control activity reduces startle potentiation during unpredictable threat (P = .031), but has no effect on startle potentiation during predictable threat (P = .609). Conclusions These results suggest that exercise reduces defensive response to unpredictable, but not predictable, threat, a dissociation that may help inform clinical indications for this behavioral intervention, as well as provide clues to its underlying neurobehavioral mechanisms.
Published: 2018
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37. Letter to the Editor from Melanson et al (second letter): 'Twice as High Diet-Induced Thermogenesis After Breakfast vs Dinner on High-Calorie as Well as Low-Calorie Meals'

Author: Edward L. Melanson and Kong Y. Chen
Subjects: medicine.medical_specialty, Calorie, Letter to the editor, business.industry, Endocrinology, Diabetes and Metabolism, Biochemistry (medical), Clinical Biochemistry, Low calorie, Thermogenesis, Diet induced thermogenesis, Biochemistry, Endocrinology, Internal medicine, medicine, Humans, Energy Intake, business, Meals, Breakfast
Published: 2020
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38. Reply to Letter to the Editor: 'No insulating effect of obesity, neither in mice nor in humans'

Author: Kong Y. Chen, Aaron M. Cypess, Robert J. Brychta, and Marc L. Reitman
Subjects: medicine.medical_specialty, Letter to the editor, Physiology, business.industry, Endocrinology, Diabetes and Metabolism, medicine.disease, Obesity, Mice, Endocrinology, Physiology (medical), Internal medicine, medicine, Animals, Humans, business, Letter to the Editor
Published: 2019

39. Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake

Author: Alexis Ayuketah, Megan Zhou, Hongyi Cai, Michael Stagliano, Ciarán G. Forde, Juen Guo, Laura A. Fletcher, Elise Costa, Irene Rozga, Rebecca Howard, Valerie L. Darcey, Ahmed M. Gharib, Mary Walter, Robert J. Brychta, Ronald Ouwerkerk, Kong Y. Chen, Paule V. Joseph, Stephanie T. Chung, Thomas M. Cassimatis, Amber B. Courville, Klaudia Raisinger, Kevin D. Hall, Shanna Yang, Peter Walter, and Suzanne McGehee
Subjects: 0301 basic medicine, Adult, Dietary Fiber, Male, Food intake, Calorie, Physiology, Energy balance, Weight Gain, Article, law.invention, processed food, 03 medical and health sciences, Eating, 0302 clinical medicine, Animal science, Randomized controlled trial, Weight loss, law, Medicine, Humans, Molecular Biology, Inpatients, business.industry, weight gain, diet quality, Cell Biology, energy balance, Calorie intake, 030104 developmental biology, Energy density, Body Composition, energy intake, Female, medicine.symptom, weight loss, business, Energy Intake, Energy Metabolism, Weight gain, 030217 neurology & neurosurgery
Abstract: We investigated whether ultra-processed foods affect energy intake in 20 weight-stable adults, aged (mean±SE) 31.2±1.6 y and BMI=27±1.5 kg/m(2). Subjects were admitted to the NIH Clinical Center and randomized to receive either ultra-processed or unprocessed diets for 2 weeks immediately followed by the alternate diet for 2 weeks. Meals were designed to be matched for presented calories, energy density, macronutrients, sugar, sodium, and fiber. Subjects were instructed to consume as much or as little as desired. Energy intake was greater during the ultra-processed diet (508±106 kcal/d; p=0.0001), with increased consumption of carbohydrate (280±54 kcal/d; p
Published: 2019

40. Sexual Dimorphisms in Adult Human Brown Adipose Tissue

Author: Molly S. Halprin, Robert J. Brychta, Aaron M. Cypess, Alana E O'Mara, Kong Y. Chen, Laura A. Fletcher, Brooks P. Leitner, Thomas M. Cassimatis, Suzanne McGehee, James W. Johnson, and Katherine Kim
Subjects: Adult, Male, Future studies, animal structures, Adolescent, Endocrinology, Diabetes and Metabolism, Glucose uptake, Medicine (miscellaneous), Adipose tissue, Physiology, 030209 endocrinology & metabolism, Article, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Endocrinology, Adipose Tissue, Brown, Fluorodeoxyglucose F18, Biopsy, Brown adipose tissue, medicine, Humans, 030212 general & internal medicine, Obesity, Young adult, Adiposity, Sex Characteristics, Nutrition and Dietetics, medicine.diagnostic_test, business.industry, medicine.anatomical_structure, Shivering, Female, medicine.symptom, business, Sex characteristics
Abstract: Objective This study aimed to quantify and compare the amount, activity, and anatomical distribution of cold-activated brown adipose tissue (BAT) in healthy, young, lean women and men. Methods BAT volume and 18 F-fluorodeoxyglucose uptake were measured by positron emission tomography and computerized tomography in 12 women and 12 men (BMI 18.5-25 kg/m2 , aged 18-35 years) after 5 hours of exposure to their coldest temperature before overt shivering. Results Women had a lower detectable BAT volume than men (P = 0.03), but there was no difference after normalizing to body size. The mean BAT glucose uptake and relative distribution of BAT did not differ by sex. 18 F-fluorodeoxyglucose uptake consistent with BAT was observed in superficial dorsocervical adipose tissue of 6 of 12 women but only 1 of 12 men (P = 0.02). This potential BAT depot would pose fewer biopsy risks than other depots. Conclusions Despite differences in adiposity and total BAT volume, we found that healthy, lean, young women and men do not differ in the relative amount, glucose uptake, and distribution of BAT. Dorsocervical 18 F-fluorodeoxyglucose uptake was more prevalent in women and may be a remnant of interscapular BAT seen in human newborns. Future studies are needed to discern how BAT contributes to whole-body thermal physiology and body weight regulation in women and men.
Published: 2019

41. Whole Body and Regional Quantification of Active Human Brown Adipose Tissue Using 18F-FDG PET/CT

Author: Katherine, Kim, Shan, Huang, Laura A, Fletcher, Alana E, O'Mara, Ilan, Tal, Robert J, Brychta, Aaron M, Cypess, Kong Y, Chen, and Brooks P, Leitner
Subjects: Adipose Tissue, Brown, Fluorodeoxyglucose F18, Positron Emission Tomography Computed Tomography, Image Processing, Computer-Assisted, Humans, Algorithms
Abstract: In endothermic animals, brown adipose tissue (BAT) is activated to produce heat for defending body temperature in response to cold. BAT's ability to expend energy has made it a potential target for novel therapies to ameliorate obesity and associated metabolic disorders in humans. Though this tissue has been well studied in small animals, BAT's thermogenic capacity in humans remains largely unknown due to the difficulties of measuring its volume, activity, and distribution. Identifying and quantifying active human BAT is commonly performed using
Published: 2019

42. Dynamic sitting: Measurement and associations with metabolic health

Author: Palmi V. Jonsson, Dane R. Van Domelen, Kong Y. Chen, Coen D.A. Stehouwer, Nanna Ýr Arnardóttir, Julianne D. van der Berg, Hans Bosma, Robert J. Brychta, Lenore J. Launer, Erlingur Johannsson, Gudny Eiriksdottir, Vilmundur Gudnason, Paolo Caserotti, Annemarie Koster, Thorarinn Sveinsson, Tamara B. Harris, Kennaradeild (HA), Faculty of Education (UA), Rannsóknarstofa í hreyfivísindum (HÍ), Research Centre for Movement Sciences (UI), Rannsóknarstofa í íþrótta- og heilsufræði (HÍ), Research Centre for Sport and Health Sciences (HÍ), Læknadeild (HÍ), Faculty of Medicine (UI), Hug- og félagsvísindasvið (HA), School of Humanities and Social Sciences (UA), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Menntavísindasvið (HÍ), School of Education (UI), Háskólinn á Akureyri, University of Akureyri, Háskóli Íslands, University of Iceland, RS: CAPHRI - R4 - Health Inequities and Societal Participation, Promovendi PHPC, Sociale Geneeskunde, MUMC+: HVC Pieken Maastricht Studie (9), MUMC+: MA Interne Geneeskunde (3), Interne Geneeskunde, RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome, MUMC+: MA Endocrinologie (9), MUMC+: MA Maag Darm Lever (9), MUMC+: MA Hematologie (9), MUMC+: MA Medische Oncologie (9), RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome, MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), MUMC+: MA Nefrologie (9), and MUMC+: MA Reumatologie (9)
Subjects: Male, Líkamsþyngdarstuðull, Disease, DISEASE, Body Mass Index, NONEXERCISE ACTIVITY THERMOGENESIS, 0302 clinical medicine, Risk Factors, Dynamic sitting, Accelerometry, Orthopedics and Sports Medicine, Sitting Position, SEDENTARY BEHAVIOR, Sedentary behavior, Middle Aged, Metabolic syndrome, TIME, Female, Waist Circumference, Adult, medicine.medical_specialty, Adolescent, Physical activity, 030209 endocrinology & metabolism, Physical Therapy, Sports Therapy and Rehabilitation, Fitness Trackers, Sitting, Article, metabolic syndrome, 03 medical and health sciences, Young Adult, BMI, AGE, sedentary behaviour, medicine, accelerometry, Hreyfing (heilsurækt), Humans, OLDER-ADULTS, Exercise, Desk, Metabolic health, business.industry, MORTALITY, 030229 sport sciences, Sedentary behaviour, PHYSICAL-ACTIVITY, Physical therapy, business, Energy Metabolism
Abstract: Article in press, Dynamic sitting, such as fidgeting and desk work, might be associated with health, but remains difficult toidentify out of accelerometry data. We examined, in a laboratory study, whether dynamic sitting can beidentified out of triaxial activity counts. Among 18 participants (56% men, 27.3 ± 6.5 years), up to 236 countsper minute were recorded in the anteroposterior and mediolateral axes during dynamic sitting using a hip-worn accelerometer. Subsequently, we examined in 621 participants (38% men, 80.0 ± 4.7 years) from theAGES-Reykjavik Study whether dynamic sitting was associated with cardio-metabolic health. Compared toparticipants who recorded the fewest dynamic sitting minutes (Q1), those with more dynamic sittingminutes had a lower BMI (Q2=−1.39 (95%CI =−2.33;–0.46); Q3=−1.87 (−2.82;–0.92); Q4=−3.38 (−4.32;–2.45)), a smaller waist circumference (Q2=−2.95 (−5.44;–0.46); Q3=−3.47 (−6.01;–0.93); Q4=−8.21 (−10.72;–5.71)), and a lower odds for the metabolic syndrome (Q2= 0.74 [0.45;1.20] Q3= 0.58 [0.36;0.95]; Q4=0.36[0.22;0.59]). Our findings suggest that dynamic sitting might be identified using accelerometry and that thisbehaviour was associated with health. This might be important given the large amounts of time peoplespend sitting. Future studies with a focus on validation, causation and physiological pathways are needed tofurther examine the possible relevance of dynamic sitting., This work was supported by the National Institute on Aging;National Institutes of Health [N01-AG-12100];FP7 People: Marie-Curie Actions (FP7- PEOPLE-2011-CIG) [PCIG09-GA-2011-293621];Icelandic Heart Association; Icelandic Parliament.
Published: 2019
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43. Human Semaphorin 3 Variants Link Melanocortin Circuit Development and Energy Balance

Author: Van Der Klaauw, AA, Croizier, S, De Oliveira, E, Stadler, LKJ, Park, S, Kong, Y, Banton, MC, Tandon, P, Hendricks, AE, Keogh, JM, Riley, SE, Papadia, S, Henning, E, Bounds, R, Bochukova, EG, Mistry, V, O'Rahilly, S, Simerly, RB, Interval, Consortium, Uk10K, Minchin, JEN, Barroso, I, Jones, EY, Bouret, SG, Farooqi, IS, University of Cambridge [UK] (CAM), Addenbrooke's Hospital, Cambridge University NHS Trust, University of Southern California (USC), Université de Lausanne = University of Lausanne (UNIL), University of Oxford, Pathogénèse des Infections vasculaires / Pathogenesis of Vascular Infections, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plymouth University, University of Edinburgh, The Wellcome Trust Sanger Institute [Cambridge], University of Colorado [Denver], Queen Mary University of London (QMUL), Vanderbilt University [Nashville], Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Studies in humans were supported by Wellcome (AAvdK, IB, ISF, 099038/Z/12/Z, 098497/Z/12/Z, WT098051), the Medical Research Council (MRC) (ISF, SOR, MRC_MC_UU_12012/5), the National Institute of Health Research (NIHR), Cambridge Biomedical Research Centre (ISF, IB, SOR), and the Bernard Wolfe Health Neuroscience Endowment (ISF). E.M.d.O. was supported by the Brazilian National Council for Scientific and Technological Development- CNPq (233690/2014-0). J.E.N.M. was supported by a joint University of Edinburgh and British Heart Foundation (BHF) Centre of Research Excellence Fellowship. S.G.B. was supported by the NIH (DK84142, DK102780, and DK118401). Structural analysis was performed by Y.K. and E.Y.J., who are supported by Cancer Research UK and the UK MRC (C375/A17721 and MR/M000141/1 to E.Y.J.) and Wellcome (203141/Z/16/Z, supporting the Wellcome Centre for Human Genetics). Whole-exome sequencing was performed as part of the UK10K consortium (a full list of investigators who contributed to the generation of the data is available from https://www.uk10k.org/). Participants in the INTERVAL randomized controlled trial were recruited with the active collaboration of NHS Blood and Transplant England (https://www.nhsbt.nhs.uk/), which has supported field work and other elements of the trial. DNA extraction and genotyping was co-funded by the NIHR, the NIHR BioResource (https://bioresource.nihr.ac.uk/), and the NIHR Cambridge Biomedical Research Centre (www.cambridgebrc.nihr.org.uk/). The academic coordinating center for INTERVAL was supported by core funding from the NIHR Blood and Transplant Research Unit in Donor Health and Genomics (NIHR BTRU-2014-10024), UK MRC (MR/L003120/1), BHF (RG/13/13/30194), and NIHR Cambridge BRC. A complete list of the investigators and contributors to the INTERVAL trial is provided (Moore et al., 2014)., CCSD, Accord Elsevier, Université de Lausanne (UNIL), University of Oxford [Oxford], Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), van der Klaauw, Agatha [0000-0001-6971-8828], Stadler, Lukas [0000-0002-7028-4390], Papadia, Sofia [0000-0002-9222-3812], O'Rahilly, Stephen [0000-0003-2199-4449], Barroso, Ines [0000-0001-5800-4520], Farooqi, Ismaa [0000-0001-7609-3504], Apollo - University of Cambridge Repository, INTERVAL, and UK10K Consortium
Subjects: Adult, Leptin, Male, Plexins, obesity, Adolescent, [SDV]Life Sciences [q-bio], Pomc, Nerve Tissue Proteins, Receptors, Cell Surface, Semaphorins, Article, Cell Line, Eating, Mice, Young Adult, Animals, Body Weight, Child, Child, Preschool, Disease Models, Animal, Energy Metabolism/genetics, Female, Genetic Variation/genetics, Homeostasis, Humans, Hypothalamus/metabolism, Leptin/metabolism, Melanocortins/metabolism, Mice, Inbred C57BL, Middle Aged, Nerve Tissue Proteins/metabolism, Neurons/metabolism, Obesity/genetics, Obesity/metabolism, Receptors, Cell Surface/metabolism, Semaphorins/genetics, Semaphorins/metabolism, Zebrafish, AgRP, Neuropilins, Semaphorin 3s, hypothalamus, Neurons, Genetic Variation, Melanocortins, [SDV] Life Sciences [q-bio], nervous system, Energy Metabolism
Abstract: Summary Hypothalamic melanocortin neurons play a pivotal role in weight regulation. Here, we examined the contribution of Semaphorin 3 (SEMA3) signaling to the development of these circuits. In genetic studies, we found 40 rare variants in SEMA3A-G and their receptors (PLXNA1-4; NRP1-2) in 573 severely obese individuals; variants disrupted secretion and/or signaling through multiple molecular mechanisms. Rare variants in this set of genes were significantly enriched in 982 severely obese cases compared to 4,449 controls. In a zebrafish mutagenesis screen, deletion of 7 genes in this pathway led to increased somatic growth and/or adiposity demonstrating that disruption of Semaphorin 3 signaling perturbs energy homeostasis. In mice, deletion of the Neuropilin-2 receptor in Pro-opiomelanocortin neurons disrupted their projections from the arcuate to the paraventricular nucleus, reduced energy expenditure, and caused weight gain. Cumulatively, these studies demonstrate that SEMA3-mediated signaling drives the development of hypothalamic melanocortin circuits involved in energy homeostasis., Graphical Abstract, Highlights • Rare variants affecting Semaphorin 3 signaling are associated with human obesity • Disruption of Semaphorin 3 signaling leads to weight gain in zebrafish and mice • Semaphorin 3 signaling promotes the development of hypothalamic melanocortin circuits, Semaphorin 3 signaling promotes the development of hypothalamic circuits, and human variants are associated with obesity.
Published: 2019
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44. Effects of colchicine in adults with metabolic syndrome: A pilot randomized controlled trial

Author: Miranda M. Broadney, Sheila M. Brady, Shahzaib M. Khan, Kong Y. Chen, Andrew P. Demidowich, Jordan A. Levine, Jack A. Yanovski, and Ginikanwa I. Onyekaba
Subjects: Adult, Blood Glucose, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Anti-Inflammatory Agents, 030209 endocrinology & metabolism, Pilot Projects, 030204 cardiovascular system & hematology, Placebo, Gastroenterology, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Insulin resistance, Randomized controlled trial, law, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Colchicine, Humans, Insulin, Obesity, Metabolic Syndrome, business.industry, Middle Aged, medicine.disease, C-Reactive Protein, chemistry, Absolute neutrophil count, Homeostatic model assessment, Female, Metabolic syndrome, Insulin Resistance, business
Abstract: AIM To evaluate the efficacy and safety of colchicine for improving metabolic and inflammatory outcomes in people with obesity and metabolic syndrome (MetS). MATERIALS AND METHODS Adults with obesity and MetS, but who did not have diabetes, were randomized to colchicine 0.6 mg or placebo capsules twice daily for 3 months. The primary outcome was change in insulin sensitivity (SI ) as estimated by insulin-modified frequently sampled intravenous glucose tolerance tests. Secondary outcomes included changes in other metabolic variables and inflammatory markers. RESULTS Of 40 participants randomized (21 colchicine, 19 placebo), 37 completed the trial. Compared with placebo, colchicine significantly reduced C-reactive protein (P
Published: 2019

45. Liraglutide and Renal Outcomes in Type 2 Diabetes

Author: Mann JFE, Ørsted DD, Brown-Frandsen K, Marso SP, Poulter NR, Rasmussen S, Tornøe K, Zinman B, Buse JB, LEADER Steering Committee and Investigators. Bergenstal R, Daniels G, Moses AC, Nauck M, Nissen S, Pocock S, Steinberg W, Stockner M, Kristensen P, Ravn LS, Zychma M, Flyvbjerg A, Ford I, Kloos RT, Schactman MJ, Sleight P, Swedberg K, Tenner SM, Akalın S, Arechavaleta R, Bain S, Babkowski MC, Benroubi M, Berard L, Comlekci A, Czupryniak L, Eliasson B, Eriksson M, Fonseca V, Franek E, Gross J, Hafidh K, Haluzik M, Hayes F, Huang YY, Jacob S, Kaddaha G, Khalil A, Kilhovd B, Laakso M, Leiter L, Lalic N, Ji L, Luedemann J, Mannucci E, Marre M, Masmiquel L, Mota M, Omar M, O’Shea D, Pan C, Petrie J, Pieber T, Pratley R, Raz I, Rea R, Rutten G, Satman I, Shestakova M, Simpson R, Smith D, Tack C, Tarnow L, Thomas N, Van Gaal L, Travert F, Vidal J, Warren M, Yoon KH, Tuttle RM, Sheerman SI, Hegedüs L, Baerwald H, Bergenstal M, Celik S, Dias C, Eder M, Fitzgibbons S, Irvhage L, Kloluckova J, Kriulianski R, McDuffie R, Moen S, Paster A, Saalfeld RM, Sankar K, Shehaj E, Swierzewska P, Tiktin M, Tovey S, Gibson CM, Chakrabarti AK, Dashe JF, Hinchey J, Leary MC, Pride Y, Wiviott S, Allen S, Mehr AP, Mutter WP, Parikh S, Ray S, Cheifetz A, Leffler D, Sheth S, Alexander E, Gaglia JL, Goessling W, Mitzner LD, Rosenberg C, Snow KJ, Wagner A, Piazza G, Abell S, Davis T, D'Emden M, Ding SA, Gilfillan C, Greenaway T, Gunawan F, Ho J, Jackson R, Kalra B, Lau SL, Lin J, MacIsaac R, Makepeace A, Malabu U, Marjason J, McCallum R, McLean M, Moin N, Petersons C, Price S, Roberts A, Roberts D, Sangla K, Stranks S, Tan Y, Thynne T, Walters J, Ward G, Wen W, Zhang J, Brix J, Feder A, Höbaus C, Höllerl F, Höller V, Kotter T, Kratz E, Krzizek EC, Leb-Stoeger U, Mader J, Mras N, Novak E, Obendorf F, Peric S, Pesau G, Prager R, Ribitsch A, Schnack C, Schernthaner G, Wascher T, Batens AH, Benhalima K, De Block C, Ernest P, Fouckova A, Jandrain B, Lapauw B, Letiexhe M, Mathieu C, Neven S, Peiffer F, Ruige J, Scheen A, Taes Y, Van Boxelaer I, Vandistel G, Van Durme Y, Verhaegen A, Alencar E, Alencar R, Almeida AC, Alves B, Alves E, Alves G, 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E, Martinez G, Martinez-Miss S, Marx P, Massara L, Mastoor M, Matfin G, Maturu A, Maurides P, May M, Mayfield R, Maynard B, Mazza A, McCann K, McCoy J, McCoy T, McCullen MK, McDaniel C, McDaniel AM, McDermott M, McDonald A, McMasters B, McMurray C, Medlin T, Meinel M, Mendez I, Menefee J, Meredith M, Merriweather M, Mersey J, Messino C, Meyer S, Meyers L, Michael D, Midyett C, Miklius A, Milford E, Miller B, Miller H, Milligan M, Minor A, Miranda-Palma B, Mirarchi N, Mittadodla S, Mittle J, Moffat A, Mohaupt S, Mohiuddin K, Mokshagundam S, Monaco S, Monsaert R, Montano-Pereira C, Montgomery A, Moody K, Moon M, Moore D, Moore L, Morawski E, Moreau C, Morin D, Moscoa C, Motzkin C, Mueller R, Munoz C, Munoz M, Myneni A, Naderi B, Nagireddy P, Naidu J, Naidu R, Naik S, Naimark R, Nardicchi M, Ndukwu I, Neller C, Netten-Foster L, Neumiller J, New T, Newman S, Newton T, Nguyen B, Nicol B, Nicol P, Ninivaggi L, Niswender K, Norman L, Noworatzky G, Nyenwe E, O'Brien H, O'Connell T, Oden W, Odugbesan A, Oliver M, Oliver T, Olmeda C, O'Neil C, Oremus R, Ortega T, Ortiz-Santos S, Osborn T, Padmanabhan S, Papacostea O, Park I, Parker A, Parker K, Parker R, Patel C, Patel M, Patel R, Patino M, Patterson S, Paulson K, Paz A, Pemba R, Pepe C, Perez J, Perez T, Perry D, Phillips B, Phillips J, Pickett A, Pinson M, Pitzer R, Poduri M, Poehls J, Poteat T, Powell L, Prasad S, Prevost J, Price E, Priest D, Prieto L, Purewal T, Purighalla R, Purighalla U, Quadrel M, Qureshi A, Radhamma R, Rafla E, Rajab H, Ramalingam R, Ramirez A, Ramirez J, Ramirez K, Ramirez M, Randall M, Rangaraj U, Rao V, Rasmussen P, Rasouli N, Ray A, Reed J, Rems L, Renaud K, Reno M, Resnick M, Reusch J, Reynolds L, Rhoton K, Rhudy J, Ricci C, Rice L, Richardson A, Richardson L, Rickard H, Rickels M, Riff D, Rightenour N, Risser J, Rizvi A, Robertson J, Robinson A, Robinson R, Rockwell M, Rodriguez JP, Rodriguez M, Rojas M, Rojas W, Rooker-Morris L, Root C, Rose M, Rosenberg R, Rosenstock J, Roth M, Ruby R, Sachson R, Sack P, Sadler RK, Sahai S, Salazar J, Salgam M, Samal A, Samson A, Sanagorski R, Sanchez A, Sandberg J, Sanderson M, Sandoval J, Santiago E, Sapp T, Saunders J, Schill J, Schott C, Schreiman R, Schu D, Schuh K, Schutta M, Schwartz J, Schweppe L, Scofield H, Scribner A, Seal J, Sealock J, Seaton B, Sedlak-Hanslik T, Seekins K, Segal M, Seggelke S, Semenza S, Sentman P, Serra M, Seshadri P, Sevilla E, Shah S, Shaheen K, Shanik M, Shaw J, Sheets M, Shellabarger C, Sher J, Shippey J, Shivaswamy V, Shomali M, Shore D, Shroff P, Siddiqui T, Siegwald A, Silver R, Simmons D, Simons R, Sinan A, Singh M, Sirinvaravong S, Skero J, Slover-Zipf J, Small S, Smith B, Smith K, Smith M, Sohl J, Solarz SH, Soler D, Sood A, Sora N, Souchet A, Soule J, Sparks J, Spector L, Speicher R, Spillers L, Spivey T, Springer N, Sprouse H, St John J, Stacey A, Stacey H, Stafford M, Stagner E, Staples K, Steadman E, Steed R, Steeves G, Steinberg H, Stell C, Stirman E, Straub K, Strock E, Sue M, Suris O, Sutton T, Tabbah I, Talsania M, Tang R, Tapia J, Taylor K, Taylor-Hancher R, Teator R, Tekateka M, Temple B, Temple K, Teodori M, Tharp P, Thethi T, Theuma P, Thomas S, Thottan A, Thrasher J, Thrasher L, Tiemeyer M, Tinney I, Tobin T, Toma S, Tovar M, Townsend J, Trantow C, Traylor H, Trevino M, Troy M, Trumper D, Tryggestad J, Tucker C, Turner J, Turney R, Tuten C, Tyzack J, Ullo L, Underkofler C, Unger J, Urdanetta R, Valdivia V, Valenti S, Vanderheiden A, Vanderlinde-Wood M, Varma C, Vasquez E, Vazquez M, Vickery D, Villafuerte B, Villegas C, Vivar J, Vivekananthan K, Vo G, Vukojicic K, Wachter A, Wahl D, Waitmann J, Walker D, Walsh J, Walsh K, Walton A, Wang A, Wardell K, Watkins S, Watkinson J, Watts M, Watwe V, Weaver N, Weber R, Wedick C, Weeks D, Weeks L, Weindorff K, Weinstein R, Weiss S, Wenger K, Wentworth M, Werner A, West M, Whelan S, White B, White J, Whitmire M, Whittington R, Wical J, Wigley C, Wilkins F, Will K, Williams A, Wilson LE, Wince M, Wine S, Winkle P, Winner C, Wise J, Witte M, Wittenmyer J, Wood C, Wood R, Woodruff C, Worthington B, Wynn D, Wysham C, Xavier P, Yela S, Yenoby L, Young L, Younus N, Yourell V, Zaid M, Zubair I., Mann, Jfe, Ørsted, Dd, Brown-Frandsen, K, Marso, Sp, Poulter, Nr, Rasmussen, S, Tornøe, K, Zinman, B, Buse, Jb, Bergenstal R, LEADER Steering Committee and Investigators., Daniels, G, Moses, Ac, Nauck, M, Nissen, S, Pocock, S, Steinberg, W, Stockner, M, Kristensen, P, Ravn, L, Zychma, M, Flyvbjerg, A, Ford, I, Kloos, Rt, Schactman, Mj, Sleight, P, Swedberg, K, Tenner, Sm, Akalın, S, Arechavaleta, R, Bain, S, Babkowski, Mc, Benroubi, M, Berard, L, Comlekci, A, Czupryniak, L, Eliasson, B, Eriksson, M, Fonseca, V, Franek, E, Gross, J, Hafidh, K, Haluzik, M, Hayes, F, Huang, Yy, Jacob, S, Kaddaha, G, Khalil, A, Kilhovd, B, Laakso, M, Leiter, L, Lalic, N, Ji, L, Luedemann, J, Mannucci, E, Marre, M, Masmiquel, L, Mota, M, Omar, M, O’Shea, D, Pan, C, Petrie, J, Pieber, T, Pratley, R, Raz, I, Rea, R, Rutten, G, Satman, I, 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Naidu, J, Naidu, R, Naik, S, Naimark, R, Nardicchi, M, Ndukwu, I, Neller, C, Netten-Foster, L, Neumiller, J, New, T, Newman, S, Newton, T, Nguyen, B, Nicol, B, Nicol, P, Ninivaggi, L, Niswender, K, Norman, L, Noworatzky, G, Nyenwe, E, O'Brien, H, O'Connell, T, Oden, W, Odugbesan, A, Oliver, M, Oliver, T, Olmeda, C, O'Neil, C, Oremus, R, Ortega, T, Ortiz-Santos, S, Osborn, T, Padmanabhan, S, Papacostea, O, Park, I, Parker, A, Parker, K, Parker, R, Patel, C, Patel, M, Patel, R, Patino, M, Patterson, S, Paulson, K, Paz, A, Pemba, R, Pepe, C, Perez, J, Perez, T, Perry, D, Phillips, B, Phillips, J, Pickett, A, Pinson, M, Pitzer, R, Poduri, M, Poehls, J, Poteat, T, Powell, L, Prasad, S, Prevost, J, Price, E, Priest, D, Prieto, L, Purewal, T, Purighalla, R, Purighalla, U, Quadrel, M, Qureshi, A, Radhamma, R, Rafla, E, Rajab, H, Ramalingam, R, Ramirez, A, J, Ramirez, Ramirez, K, Ramirez, M, Randall, M, Rangaraj, U, Rao, V, Rasmussen, P, Rasouli, N, Ray, A, Reed, J, Rems, L, Renaud, K, Reno, M, Resnick, M, Reusch, J, Reynolds, L, Rhoton, K, Rhudy, J, Ricci, C, Rice, L, Richardson, A, Richardson, L, Rickard, H, Rickels, M, Riff, D, Rightenour, N, Risser, J, Rizvi, A, Robertson, J, Robinson, A, Robinson, R, Rockwell, M, Rodriguez, Jp, Rodriguez, M, Rojas, M, Rojas, W, Rooker-Morris, L, Root, C, Rose, M, Rosenberg, R, Rosenstock, J, Roth, M, Ruby, R, Sachson, R, Sack, P, Sadler, Rk, Sahai, S, J, Salazar, Salgam, M, Samal, A, Samson, A, Sanagorski, R, Sanchez, A, Sandberg, J, Sanderson, M, Sandoval, J, Santiago, E, Sapp, T, Saunders, J, Schill, J, Schott, C, Schreiman, R, Schu, D, Schuh, K, Schutta, M, Schwartz, J, Schweppe, L, Scofield, H, Scribner, A, Seal, J, Sealock, J, Seaton, B, Sedlak-Hanslik, T, Seekins, K, Segal, M, Seggelke, S, Semenza, S, Sentman, P, Serra, M, Seshadri, P, Sevilla, E, Shah, S, Shaheen, K, Shanik, M, Shaw, J, Sheets, M, Shellabarger, C, Sher, J, Shippey, J, Shivaswamy, V, Shomali, M, Shore, D, Shroff, P, Siddiqui, T, Siegwald, A, Silver, R, Simmons, D, Simons, R, Sinan, A, Singh, M, Sirinvaravong, S, Skero, J, Slover-Zipf, J, Small, S, Smith, B, Smith, K, Smith, M, Sohl, J, Solarz, Sh, Soler, D, Sood, A, Sora, N, Souchet, A, Soule, J, Sparks, J, Spector, L, Speicher, R, Spillers, L, Spivey, T, Springer, N, Sprouse, H, St John, J, Stacey, A, Stacey, H, Stafford, M, Stagner, E, Staples, K, Steadman, E, Steed, R, Steeves, G, Steinberg, H, Stell, C, Stirman, E, Straub, K, Strock, E, Sue, M, Suris, O, Sutton, T, Tabbah, I, Talsania, M, Tang, R, Tapia, J, Taylor, K, Taylor-Hancher, R, Teator, R, Tekateka, M, Temple, B, Temple, K, Teodori, M, Tharp, P, Thethi, T, Theuma, P, Thomas, S, Thottan, A, Thrasher, J, Thrasher, L, Tiemeyer, M, Tinney, I, Tobin, T, Toma, S, Tovar, M, Townsend, J, Trantow, C, Traylor, H, Trevino, M, Troy, M, Trumper, D, Tryggestad, J, Tucker, C, Turner, J, Turney, R, Tuten, C, Tyzack, J, Ullo, L, Underkofler, C, Unger, J, Urdanetta, R, Valdivia, V, Valenti, S, Vanderheiden, A, Vanderlinde-Wood, M, Varma, C, Vasquez, E, Vazquez, M, Vickery, D, Villafuerte, B, Villegas, C, Vivar, J, Vivekananthan, K, Vo, G, Vukojicic, K, Wachter, A, Wahl, D, Waitmann, J, Walker, D, Walsh, J, Walsh, K, Walton, A, Wang, A, Wardell, K, Watkins, S, Watkinson, J, Watts, M, Watwe, V, Weaver, N, Weber, R, Wedick, C, Weeks, D, Weeks, L, Weindorff, K, Weinstein, R, Weiss, S, Wenger, K, Wentworth, M, Werner, A, West, M, Whelan, S, White, B, White, J, Whitmire, M, Whittington, R, Wical, J, Wigley, C, Wilkins, F, Will, K, Williams, A, Wilson, Le, Wince, M, Wine, S, Winkle, P, Winner, C, Wise, J, Witte, M, Wittenmyer, J, Wood, C, Wood, R, Woodruff, C, Worthington, B, Wynn, D, Wysham, C, Xavier, P, Yela, S, Yenoby, L, Young, L, Younus, N, Yourell, V, Zaid, M, Zubair, I., Mann J.F.E., Orsted D.D., Brown-Frandsen K., Marso S.P., Poulter N.R., Rasmussen S., Tornoe K., Zinman B., Buse J.B., and Buscemi S.
Subjects: Male, Settore MED/09 - Medicina Interna, Acute Kidney Injury, Aged, Albuminuria, Creatinine, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Double-Blind Method, Female, Follow-Up Studies, Glomerular Filtration Rate, Glucagon-Like Peptide 1, Humans, Hypoglycemic Agents, Intention to Treat Analysis, Kidney Failure, Chronic, Liraglutide, Middle Aged, Type 2 diabetes, 030204 cardiovascular system & hematology, urologic and male genital diseases, GLOMERULAR-FILTRATION-RATE, KIDNEY-FUNCTION, DISEASE, law.invention, Kidney Failure, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Medicine, Settore MED/49 - Scienze Tecniche Dietetiche Applicate, Chronic, RISK, Kidney, Acute kidney injury, 11 Medical And Health Sciences, General Medicine, medicine.anatomical_structure, TRIAL, liraglutide, randomized controlled trial, type 2 diabetes, renal outcomes, Life Sciences & Biomedicine, Type 2, medicine.drug, medicine.medical_specialty, Renal function, 030209 endocrinology & metabolism, CARDIOVASCULAR OUTCOMES, Follow-Up Studie, 03 medical and health sciences, Medicine, General & Internal, General & Internal Medicine, Diabetes mellitus, Internal medicine, Diabetes Mellitus, Intensive care medicine, Science & Technology, business.industry, MORTALITY, medicine.disease, INTENSIVE GLUCOSE CONTROL, INDIVIDUALS, chemistry, Diabetic Nephropathie, LEADER Steering Committee and Investigators, business
Abstract: BACKGROUND: In a randomized, controlled trial that compared liraglutide, a glucagon-like peptide 1 analogue, with placebo in patients with type 2 diabetes and high cardiovascular risk who were receiving usual care, we found that liraglutide resulted in lower risks of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) and death. However, the long-term effects of liraglutide on renal outcomes in patients with type 2 diabetes are unknown. METHODS: We report the prespecified secondary renal outcomes of that randomized, controlled trial in which patients were assigned to receive liraglutide or placebo. The secondary renal outcome was a composite of new-onset persistent macroalbuminuria, persistent doubling of the serum creatinine level, end-stage renal disease, or death due to renal disease. The risk of renal outcomes was determined with the use of time-to-event analyses with an intention-to-treat approach. Changes in the estimated glomerular filtration rate and albuminuria were also analyzed. RESULTS: A total of 9340 patients underwent randomization, and the median follow-up of the patients was 3.84 years. The renal outcome occurred in fewer participants in the liraglutide group than in the placebo group (268 of 4668 patients vs. 337 of 4672; hazard ratio, 0.78; 95% confidence interval [CI], 0.67 to 0.92; P=0.003). This result was driven primarily by the new onset of persistent macroalbuminuria, which occurred in fewer participants in the liraglutide group than in the placebo group (161 vs. 215 patients; hazard ratio, 0.74; 95% CI, 0.60 to 0.91; P=0.004). The rates of renal adverse events were similar in the liraglutide group and the placebo group (15.1 events and 16.5 events per 1000 patient-years), including the rate of acute kidney injury (7.1 and 6.2 events per 1000 patient-years, respectively). CONCLUSIONS: This prespecified secondary analysis shows that, when added to usual care, liraglutide resulted in lower rates of the development and progression of diabetic kidney disease than placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048 .).
Published: 2017

46. Cold-induced thermogenesis in humans

Author: Kong Y. Chen and R J Brychta
Subjects: 0301 basic medicine, medicine.medical_specialty, Cold induced thermogenesis, Population, Medicine (miscellaneous), Adipose tissue, Physiology, Human metabolism, 030209 endocrinology & metabolism, Biology, Article, Clothing, 03 medical and health sciences, 0302 clinical medicine, Adipose Tissue, Brown, Internal medicine, Brown adipose tissue, medicine, Animals, Humans, education, education.field_of_study, Nutrition and Dietetics, Age Factors, Thermogenesis, Thermoregulation, Cold Temperature, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Models, Animal, Basal metabolic rate, Energy Metabolism
Abstract: A basic property of endothermic thermoregulation is the ability to generate heat by increasing metabolism in response to cold ambient temperatures to maintain a stable core body temperature. This process, known as cold-induced thermogenesis (CIT), has been measured in humans as early as 1780 by Antoine Lavoisier, but has found renewed interest because of the recent 'rediscovery' of thermogenic, cold-activated brown adipose tissue (BAT) in adult humans. In this review, we summarize some of the key findings of the work involving CIT over the past two centuries and highlight some of the seminal studies focused on this topic. There has been a substantial range of variability in the reported CIT in these studies, from 0 to 280% above basal metabolism. We identify and discuss several potential sources of this variability, including both methodological (measurement device, cold exposure temperature and duration) and biological (age and body composition of subject population) discrepancies. These factors should be considered when measuring CIT going forward to better assess whether BAT or other thermogenic organs are viable targets to combat chronic positive energy balance based on their relative capacities to elevate human metabolism.
Published: 2016
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47. A Randomized Controlled Trial to Prevent Depression and Ameliorate Insulin Resistance in Adolescent Girls at Risk for Type 2 Diabetes

Author: Courtney K. Pickworth, Eric Stice, Katherine Thompson, Lisa M. Shank, Marian Tanofsky-Kraff, Jack A. Yanovski, Ovidiu A. Galescu, Anna Vannucci, Sheila M. Brady, Rachel M. Radin, Andrew P. Demidowich, Cara H. Olsen, Lauren B. Shomaker, Amber B. Courville, Sara A. Armaiz-Flores, Omni Cassidy, Kong Y. Chen, and Nichole R. Kelly
Subjects: 050103 clinical psychology, medicine.medical_specialty, Adolescent, medicine.medical_treatment, 030209 endocrinology & metabolism, Type 2 diabetes, Overweight, Article, law.invention, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Randomized controlled trial, law, Internal medicine, Epidemiology, medicine, Humans, 0501 psychology and cognitive sciences, Family history, Child, General Psychology, Depression (differential diagnoses), Cognitive Behavioral Therapy, Depression, business.industry, 05 social sciences, medicine.disease, Cognitive behavioral therapy, Psychiatry and Mental health, Treatment Outcome, Diabetes Mellitus, Type 2, Physical therapy, Female, Insulin Resistance, medicine.symptom, business
Abstract: Prospective data suggest depressive symptoms worsen insulin resistance and accelerate type 2 diabetes (T2D) onset.We sought to determine whether reducing depressive symptoms in overweight/obese adolescents at risk for T2D would increase insulin sensitivity and mitigate T2D risk.We conducted a parallel-group, randomized controlled trial comparing a 6-week cognitive-behavioral (CB) depression prevention group with a 6-week health education (HE) control group in 119 overweight/obese adolescent girls with mild-to-moderate depressive symptoms (Center for Epidemiological Studies-Depression Scale [CES-D] ≥16) and T2D family history. Primary outcomes were baseline to post-intervention changes in CES-D and whole body insulin sensitivity index (WBISI), derived from 2-h oral glucose tolerance tests. Outcome changes were compared between groups using ANCOVA, adjusting for respective baseline outcome, puberty, race, facilitator, T2D family history degree, baseline age, adiposity, and adiposity change. Multiple imputation was used for missing data.Depressive symptoms decreased (p 0.001) in CB and HE from baseline to posttreatment, but did not differ between groups (ΔCESD = -12 vs. -11, 95 % CI difference = -4 to +1, p = 0.31). Insulin sensitivity was stable (p 0.29) in CB and HE (ΔWBISI = 0.1 vs. 0.2, 95 % CI difference = -0.6 to +0.4, p = 0.63). Among all participants, reductions in depressive symptoms were associated with improvements in insulin sensitivity (p = 0.02).Girls at risk for T2D displayed reduced depressive symptoms following 6 weeks of CB or HE. Decreases in depressive symptoms related to improvements in insulin sensitivity. Longer-term follow-up is needed to determine whether either program causes sustained decreases in depressive symptoms and improvements in insulin sensitivity.The trial was registered with clinicaltrials.gov (NCT01425905).
Published: 2016
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48. Self-reported and objectively measured physical activity levels among Hispanic/Latino adults with type 2 diabetes

Author: Wendy C. Bevier, Charis B. Hoppe, Jessikah Morales Glass, Kong Y. Chen, Arianna J. Larez, David Kerr, and Namino M. Glantz
Subjects: physical activity and health, Male, Research design, medicine.medical_specialty, Waist, Endocrinology, Diabetes and Metabolism, Hispanic, Psychological intervention, Physical activity, 030209 endocrinology & metabolism, Type 2 diabetes, Clinical Care/Education/Nutrition, Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Diabetes mellitus, medicine, Humans, 030212 general & internal medicine, exercise, business.industry, Hispanic or Latino, Middle Aged, RC648-665, medicine.disease, Actigraphy, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Physical therapy, Female, Observational study, type 2 diabetes, Self Report, business, Body mass index
Abstract: ObjectiveIn the USA, minority populations face a disproportionate burden from type 2 diabetes (T2D), in whom physical activity (PA) is recommended. The aim of this study was to determine levels of PA among a community of free-living Hispanic/Latino adults with T2D using a research accelerometer, a consumer device and a pictogram self-assessment questionnaire.Research design and methodsThis was a cross-sectional, observational study. Participants (57 women and 31 men, body mass index (kg/m2) 32.2±7.9 and 29.9±4.5, waist circumference 97.1±30.1 and 93.7±33.0 cm and hemoglobin A1c 8.0±2.0 and 8.1%±1.8%, respectively) wore an ActiGraph (AG) on the hip and a Fitbit (FB) on the wrist for 1 week to estimate daily steps and energy expenditure (EE). Participants reported type and intensity of PA using English-language or Spanish-language pictograms and a 10-point Likert scale (1=‘not active’ to 10=‘very, very active’).ResultsSteps per day were not normally distributed; AG median steps/weekday (Monday–Friday) was 6990 (range 1091–25 884) compared with 9329 (288–31 669) using FB (p≤0.01). Both devices recorded significantly more steps on weekdays versus weekends (p≤0.05). EE was also higher during the week. AG and FB were highly correlated to each other (pConclusionsBoth objectively measured and self-reported levels of PA in Hispanic/Latino adults with T2D challenge the assumption that lack of PA may be commonplace for this group. AG and FB are different in their measurement of PA but are significantly correlated. New strategies, including use of pictograms, for interventions need to be considered if further increases or changes in PA are to be used as T2D therapy.Trial registration numberNCT03736486
Published: 2020
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49. Metreleptin-mediated improvements in insulin sensitivity are independent of food intake in humans with lipodystrophy

Author: Areli Valencia, Rebecca J. Brown, Peter Walter, Sungyoung Auh, Amber B. Courville, Hongyi Cai, Mary Walter, Megan Startzell, Elaine Cochran, Shanna Bernstein, H. Martin Garraffo, Robert J. Brychta, Ronald Ouwerkerk, Phillip Gorden, Ahmed M. Gharib, and Kong Y. Chen
Subjects: Adult, Male, 0301 basic medicine, Leptin, medicine.medical_specialty, Adolescent, Lipodystrophy, 030209 endocrinology & metabolism, 03 medical and health sciences, chemistry.chemical_compound, Metreleptin, Eating, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Medicine, Lipolysis, Humans, Triglycerides, Aged, Cross-Over Studies, Leptin Deficiency, Triglyceride, business.industry, digestive, oral, and skin physiology, General Medicine, Middle Aged, medicine.disease, Crossover study, 030104 developmental biology, Endocrinology, Liver, chemistry, Commentary, Female, Clinical Medicine, Insulin Resistance, business, hormones, hormone substitutes, and hormone antagonists
Abstract: Background Recombinant leptin (metreleptin) ameliorates hyperphagia and metabolic abnormalities in leptin-deficient humans with lipodystrophy. We aimed to determine whether metreleptin improves glucose and lipid metabolism in humans when food intake is held constant. Methods Patients with lipodystrophy were hospitalized for 19 days, with food intake held constant by a controlled diet in an inpatient metabolic ward. In a nonrandomized, crossover design, patients previously treated with metreleptin (n = 8) were continued on metreleptin for 5 days and then taken off metreleptin for the next 14 days (withdrawal cohort). This order was reversed in metreleptin-naive patients (n = 14), who were reevaluated after 6 months of metreleptin treatment on an ad libitum diet (initiation cohort). Outcome measurements included insulin sensitivity by hyperinsulinemic-euglycemic clamp, fasting glucose and triglyceride levels, lipolysis measured using isotopic tracers, and liver fat by magnetic resonance spectroscopy. Results With food intake constant, peripheral insulin sensitivity decreased by 41% after stopping metreleptin for 14 days (withdrawal cohort) and increased by 32% after treatment with metreleptin for 14 days (initiation cohort). In the initiation cohort only, metreleptin decreased fasting glucose by 11% and triglycerides by 41% and increased hepatic insulin sensitivity. Liver fat decreased from 21.8% to 18.7%. In the initiation cohort, changes in lipolysis were not independent of food intake, but after 6 months of metreleptin treatment on an ad libitum diet, lipolysis decreased by 30% (palmitate turnover) to 35% (glycerol turnover). Conclusion Using lipodystrophy as a human model of leptin deficiency and replacement, we show that metreleptin improves insulin sensitivity and decreases hepatic and circulating triglycerides and that these improvements are independent of its effects on food intake. Trial registration ClinicalTrials.gov NCT01778556FUNDING. This research was supported by the intramural research program of the NIDDK.
Published: 2018

50. Regulation of Human Adipose Tissue Activation, Gallbladder Size, and Bile Acid Metabolism by a β3-Adrenergic Receptor Agonist

Author: Courtney J. Duckworth, James W. Johnson, Suzanne McGehee, Peter Herscovitch, H. Martin Garraffo, Michael A. Kiebish, Alison S. Baskin, Laura A. Fletcher, Brooks P. Leitner, Niven R. Narain, Cheryl Cero, Corina Millo, Fei Gao, Joyce D. Linderman, Peter Walter, William Dieckmann, Robert J. Brychta, Kong Y. Chen, Esti Anflick-Chames, Vladimir Tolstikov, Hongyi Cai, Alana E O'Mara, Emily Y. Chen, Aaron M. Cypess, and Shan Huang
Subjects: 0301 basic medicine, Agonist, Adult, medicine.medical_specialty, Adolescent, medicine.drug_class, Endocrinology, Diabetes and Metabolism, Adipose tissue, White adipose tissue, Bile Acids and Salts, 03 medical and health sciences, Mice, Young Adult, Adipose Tissue, Brown, Internal medicine, Brown adipose tissue, Receptors, Adrenergic, beta, Internal Medicine, medicine, Lipolysis, Animals, Humans, RNA, Messenger, Aged, Aged, 80 and over, business.industry, Gallbladder, Thermogenesis, Adrenergic beta-Agonists, Middle Aged, Pharmacology and Therapeutics, Healthy Volunteers, Mice, Inbred C57BL, Thiazoles, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Receptors, Adrenergic, beta-3, Acetanilides, Mirabegron, business, medicine.drug
Abstract: β3-adrenergic receptor (AR) agonists are approved to treat only overactive bladder. However, rodent studies suggest that these drugs could have other beneficial effects on human metabolism. We performed tissue receptor profiling and showed that the human β3-AR mRNA is also highly expressed in gallbladder and brown adipose tissue (BAT). We next studied the clinical implications of this distribution in 12 healthy men given one-time randomized doses of placebo, the approved dose of 50 mg, and 200 mg of the β3-AR agonist mirabegron. There was a more-than-dose-proportional increase in BAT metabolic activity as measured by [18F]-2-fluoro-D-2-deoxy-d-glucose positron emission tomography/computed tomography (medians 0.0 vs. 18.2 vs. 305.6 mL ⋅ mean standardized uptake value [SUVmean] ⋅ g/mL). Only the 200-mg dose elevated both nonesterified fatty acids (68%) and resting energy expenditure (5.8%). Previously undescribed increases in gallbladder size (35%) and reductions in conjugated bile acids were also discovered. Therefore, besides urinary bladder relaxation, the human β3-AR contributes to white adipose tissue lipolysis, BAT thermogenesis, gallbladder relaxation, and bile acid metabolism. This physiology should be considered in the development of more selective β3-AR agonists to treat obesity-related complications.
Published: 2018

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