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2. Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry
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Jitendra PS. Sawhney, Veerappa A. Kothiwale, Vikas Bisne, Rajashekhar Durgaprasad, Praveen Jadhav, Manoj Chopda, Velam Vanajakshamma, Ramdhan Meena, Govindan Vijayaraghavan, Kamaldeep Chawla, Jagan Allu, Karen S. Pieper, A. John Camm, Ajay K. Kakkar, Jean-Pierre Bassand, David A. Fitzmaurice, Samuel Z. Goldhaber, Shinya Goto, Sylvia Haas, Werner Hacke, Lorenzo G. Mantovani, Frank Misselwitz, Alexander G.G. Turpie, Martin van Eickels, Freek W.A. Verheugt, Gloria Kayani, Keith A.A. Fox, Bernard J. Gersh, Hector Lucas Luciardi, Harry Gibbs, Marianne Brodmann, Frank Cools, Antonio Carlos Pereira Barretto, Stuart J. Connolly, Alex Spyropoulos, John Eikelboom, Ramon Corbalan, Dayi Hu, Petr Jansky, Jørn Dalsgaard Nielsen, Hany Ragy, Pekka Raatikainen, Jean-Yves Le Heuzey, Harald Darius, Matyas Keltai, Sanjay Kakkar, Jitendra Pal Singh Sawhney, Giancarlo Agnelli, Giuseppe Ambrosio, Yukihiro Koretsune, Carlos Jerjes Sánchez Díaz, Hugo Ten Cate, Dan Atar, Janina Stepinska, Elizaveta Panchenko, Toon Wei Lim, Barry Jacobson, Seil Oh, Xavier Viñolas, Marten Rosenqvist, Jan Steffel, Pantep Angchaisuksiri, Ali Oto, Alex Parkhomenko, Wael Al Mahmeed, David Fitzmaurice, D.Y. Hu, K.N. Chen, Y.S. Zhao, H.Q. Zhang, J.Z. Chen, S.P. Cao, D.W. Wang, Y.J. Yang, W.H. Li, Y.H. Yin, G.Z. Tao, P. Yang, Y.M. Chen, S.H. He, Ying Wang, Yong Wang, G.S. Fu, X. Li, T.G. Wu, X.S. Cheng, X.W. Yan, R.P. Zhao, M.S. Chen, L.G. Xiong, P. Chen, Y. Jiao, Y. Guo, L. Xue, F.Z. Wang, H. Li, Z.M. Yang, C.L. Bai, J. Chen, J.Y. Chen, X. Chen, S. Feng, Q.H. Fu, X.J. Gao, W.N. Guo, R.H. He, X.A. He, X.S. Hu, X.F. Huang, B. Li, J. Li, L. Li, Y.H. Li, T.T. Liu, W.L. Liu, Y.Y. Liu, Z.C. Lu, X.L. Luo, T.Y. Ma, J.Q. Peng, X. Sheng, X.J. Shi, Y.H. Sun, G. Tian, K. Wang, L. Wang, R.N. Wu, Q. Xie, R.Y. Xu, J.S. Yang, L.L. Yang, Q. Yang, Y. Ye, H.Y. Yu, J.H. Yu, T. Yu, H. Zhai, Q. Zhan, G.S. Zhang, Q. Zhang, R. Zhang, Y. Zhang, W.Y. Zheng, B. Zhou, Z.H. Zhou, X.Y. Zhu, S. Kakkar, J.P.S. Sawhney, P. Jadhav, R. Durgaprasad, A.G. Ravi Shankar, R.K. Rajput, K. Bhargava, R. Sarma, A. Srinivas, D. Roy, U.M. Nagamalesh, M. Chopda, R. Kishore, G. Kulkarni, P. Chandwani, R.A. Pothiwala, M. Padinhare Purayil, S. Shah, K. Chawla, V.A. Kothiwale, B. Raghuraman, G. Vijayaraghavan, V.M. Vijan, G. Bantwal, V. Bisne, A. Khan, J.B. Gupta, S. Kumar, D. Jain, S. Abraham, D. Adak, A. Barai, H. Begum, P. Bhattacharjee, M. Dargude, D. Davies, B. Deshpande, P. Dhakrao, V. Dhyani, S. Duhan, M. Earath, A. Ganatra, S. Giradkar, V. Jain, R. Karthikeyan, L. Kasala, S. Kaur, S. Krishnappa, A. Lawande, B. Lokesh, N. Madarkar, R. Meena, P. More, D. Naik, K. Prashanth, M. Rao, N.M. Rao, N. Sadhu, D. Shah, M. Sharma, P. Shiva, S. Singhal, S. Suresh, V. Vanajakshamma, S.G. Panse, Y. Koretsune, S. Kanamori, K. Yamamoto, K. Kumagai, Y. Katsuda, K. Sadamatsu, F. Toyota, Y. Mizuno, I. Misumi, H. Noguchi, S. Ando, T. Suetsugu, M. Minamoto, Hiroshi Oda, K. Shiraishi, S. Adachi, K. Chiba, H. Norita, M. Tsuruta, T. Koyanagi, H. Ando, T. Higashi, K. Okada, S. Azakami, S. Komaki, K. Kumeda, T. Murayama, J. Matsumura, Y. Oba, R. Sonoda, K. Goto, K. Minoda, Y. Haraguchi, H. Suefuji, H. Miyagi, H. Kato, Tadashi Nakamura, Tsugihiro Nakamura, H. Nandate, R. Zaitsu, Yoshihisa Fujiura, A. Yoshimura, H. Numata, J. Ogawa, H. Tatematsu, Y. Kamogawa, K. Murakami, Y. Wakasa, M. Yamasawa, H. Maekawa, S. Abe, H. Kihara, S. Tsunoda, Katsumi Saito, Kazuyuki Saito, T. Fudo, K. Obunai, H. Tachibana, I. Oba, T. Kuwahata, S. Higa, M. Gushiken, T. Eto, H. Yoshida, D. Ikeda, Yoshitake Fujiura, M. Ishizawa, M. Nakatsuka, K. Murata, C. Ogurusu, M. Shimoyama, M. Akutsu, I. Takamura, F. Hoshino, N. Yokota, T. Iwao, K. Tsuchida, M. Takeuchi, Y. Hatori, Y. Kitami, Yoichi Nakamura, R. Oyama, M. Ageta, Hiroyuki Oda, Y. Go, K. Mishima, T. Unoki, S. Morii, Yuhei Shiga, H. Sumi, T. Nagatomo, K. Sanno, K. Fujisawa, Y. Atsuchi, T. Nagoshi, T. Seto, T. Tabuchi, M. Kameko, K. Nii, K. Oshiro, H. Takezawa, S. Nagano, N. Miyamoto, M. Iwaki, Yuichiro Nakamura, M. Fujii, M. Okawa, Masahiko Abe, Masatake Abe, Mitsunori Abe, T. Saito, T. Mito, K. Nagao, J. Minami, T. Mita, I. Sakuma, T. Taguchi, S. Marusaki, H. Doi, M. Tanaka, T. Fujito, M. Matsuta, T. Kusumoto, S. Kakinoki, K. Ashida, N. Yoshizawa, J. Agata, O. Arasaki, M. Manita, M. Ikemura, S. Fukuoka, H. Murakami, S. Matsukawa, Y. Hata, T. Taniguchi, T. Ko, H. Kubo, M. Imamaki, M. Akiyama, M. Inagaki, H. Odakura, T. Ueda, Y. Katsube, A. Nakata, H. Watanabe, M. Techigawara, M. Igarashi, K. Taga, T. Kimura, S. Tomimoto, M. Shibuya, M. Nakano, K. Ito, T. Seo, S. Hiramitsu, H. Hosokawa, M. Hoshiai, M. Hibino, K. Miyagawa, Hajime Horie, N. Sugishita, Yukio Shiga, A. Soma, K. Neya, Tetsuro Yoshida, Tomoki Yoshida, M. Mizuguchi, M. Ishiguro, T. Minagawa, M. Wada, H. Mukawa, F. Okuda, S. Nagasaka, Y. Abe, Sen Adachi, Susumu Adachi, T. Adachi, K. Akahane, T. Amano, K. Aoki, T. Aoyama, H. Arai, S. Arima, T. Arino, H. Asano, T. Asano, J. Azuma, T. Baba, T. Betsuyaku, H. Chibana, H. Date, J. Doiuchi, Y. Emura, M. Endo, Y. Fujii, R. Fujiki, A. Fujisawa, Y. Fujisawa, T. Fukuda, T. Fukui, N. Furukawa, T. Furukawa, W. Furumoto, T. Goto, M. Hamaoka, N. Hanazono, K. Hasegawa, T. Hatsuno, Y. Hayashi, K. Higuchi, K. Hirasawa, H. Hirayama, M. Hirose, S. Hirota, M. Honda, Hideki Horie, T. Ido, O. Iiji, H. Ikeda, K. Ikeda, K. Ikeoka, M. Imaizumi, H. Inaba, T. Inoue, F. Iseki, A. Ishihara, N. Ishioka, N. Ito, T. Iwase, H. Kakuda, J. Kamata, H. Kanai, H. Kanda, M. Kaneko, H. Kano, T. Kasai, T. Kato, Y. Kato, Y. Kawada, K. Kawai, K. Kawakami, S. Kawakami, T. Kawamoto, S. Kawano, J. Kim, T. Kira, H. Kitazawa, H. Kitazumi, T. Kito, T. Kobayashi, T. Koeda, J. Kojima, H. Komatsu, I. Komatsu, Y. Koshibu, T. Kotani, T. Kozuka, Y. Kumai, T. Kumazaki, I. Maeda, K. Maeda, Y. Maruyama, S. Matsui, K. Matsushita, Y. Matsuura, K. Mineoi, H. Mitsuhashi, N. Miura, S. Miyaguchi, S. Miyajima, H. Miyamoto, A. Miyashita, S. Miyata, I. Mizuguchi, A. Mizuno, T. Mori, O. Moriai, K. Morishita, O. Murai, Sho Nagai, Shunichi Nagai, E. Nagata, H. Nagata, A. Nakagomi, S. Nakahara, M. Nakamura, R. Nakamura, N. Nakanishi, T. Nakayama, R. Nakazato, T. Nanke, J. Nariyama, Y. Niijima, H. Niinuma, Y. Nishida, Y. Nishihata, K. Nishino, H. Nishioka, K. Nishizawa, I. Niwa, K. Nomura, S. Nomura, M. Nozoe, T. Ogawa, N. Ohara, M. Okada, K. Okamoto, H. Okita, M. Okuyama, H. Ono, T. Ono, Y. Onuki Pearce, S. Oriso, A. Ota, E. Otaki, Y. Saito, H. Sakai, N. Sakamoto, Y. Sakamoto, Y. Samejima, Y. Sasagawa, H. Sasaguri, A. Sasaki, T. Sasaki, Kazuki Sato, Kiyoharu Sato, M. Sawano, S. Seki, Y. Sekine, Y. Seta, K. Sezaki, N. Shibata, Y. Shiina, H. Shimono, Y. Shimoyama, T. Shindo, H. Shinohara, R. Shinohe, T. Shinozuka, T. Shirai, T. Shiraiwa, Y. Shozawa, T. Suga, C. Sugimoto, Kazuo Suzuki, Keita Suzuki, Shu Suzuki, Shunji Suzuki, Susumu Suzuki, Y. Suzuki, M. Tada, A. Taguchi, T. Takagi, Y. Takagi, K. Takahashi, S. Takahashi, H. Takai, C. Takanaka, S. Take, H. Takeda, K. Takei, K. Takenaka, T. Tana, G. Tanabe, K. Taya, H. Teragawa, S. Tohyo, S. Toru, Y. Tsuchiya, T. Tsuji, K. Tsuzaki, H. Uchiyama, O. Ueda, Y. Ueyama, N. Wakaki, T. Wakiyama, T. Washizuka, M. Watanabe, T. Yamada, T. Yamagishi, H. Yamaguchi, Kenichi Yamamoto, Kentaro Yamamoto, Kunihiko Yamamoto, T. Yamamoto, M. Yamaura, M. Yamazoe, K. Yasui, Y. Yokoyama, K. Yoshida, T.W. Lim, C.K. Ching, C.G. Foo, J.H. Chow, D.D. Chen, F.R. Jaufeerally, Y.M. Lee, G. Lim, W.T. Lim, S. Thng, S.Y. Yap, C. Yeo, S. Oh, H.N. Pak, J.-B. Kim, J.H. Kim, S.-W. Jang, D.H. Kim, D.R. Ryu, S.W. Park, D.-K. Kim, D.J. Choi, Y.S. Oh, M.-C. Cho, S.-H. Kim, H.-K. Jeon, D.-G. Shin, J.S. Park, H.K. Park, S.-J. Han, J.H. Sung, J.-G. Cho, G.-B. Nam, Y.K. On, H.E. Lim, J.J. Kwak, T.-J. Cha, T.J. Hong, S.H. Park, J.H. Yoon, N.-H. Kim, K.-S. Kim, B.C. Jung, G.-S. Hwang, C.-J. Kim, D.B. Kim, J.J. Ahn, H.J. An, H. Bae, A.L. Baek, W.J. Chi, E.A. Choi, E.H. Choi, H.K. Choi, H.S. Choi, S. Han, E.S. Heo, K.O. Her, S.W. Hwang, E.M. Jang, H.-S. Jang, S. Jang, H.-G. Jeon, S.R. Jeon, Y.R. Jeon, H.K. Jeong, I.-A. Jung, Hyeon Jeong Kim, Hyun Ju Kim, Ji Seon Kim, Jung Sook Kim, J.A. Kim, K.T. Kim, M.S. Kim, Sang Hee Kim, Sang Hyun Kim, Y.-I. Kim, C.S. Lee, E.H. Lee, G.H. Lee, H.Y. Lee, H.-Y. Lee, K.H. Lee, K.R. Lee, M.S. Lee, M.-Y. Lee, R.W. Lee, S.E. Lee, S.H. Lee, S. Lee, W.Y. Lee, I.K. Noh, A.R. Park, B.R. Park, H.N. Park, J.H. Park, M. Park, Y. Park, S.-Y. Seo, J. Shim, J.H. Sim, Y.M. Sohn, W.S. Son, Y.S. Son, H.J. Song, H.K. Wi, J.J. Woo, S. Ye, K.H. Yim, K.M. Yoo, E.J. Yoon, S.Y. Yun, P. Angchaisuksiri, S. Chawanadelert, P. Mongkolwongroj, K. Kanokphatcharakun, S. Cheewatanakornkul, T. Laksomya, S. Pattanaprichakul, T. Chantrarat, S. Rungaramsin, S. Silaruks, W. Wongcharoen, K. Siriwattana, K. Likittanasombat, P. Katekangplu, W. Boonyapisit, D. Cholsaringkarl, B. Chatlaong, P. Chattranukulchai, Y. Santanakorn, P. Hutayanon, P. Khunrong, T. Bunyapipat, S. Jai-Aue, P. Kaewsuwanna, P. Bamungpong, S. Gunaparn, S. Hongsuppinyo, R. Inphontan, R. Khattaroek, K. Khunkong, U. Kitmapawanont, C. Kongsin, B. Naratreekoon, S. Ninwaranon, J. Phangyota, A. Phrommintikul, P. Phunpinyosak, K. Pongmorakot, S. Poomiphol, N. Pornnimitthum, S. Pumprueg, S. Ratchasikaew, K. Sanit, K. Sawanyawisuth, B. Silaruks, R. Sirichai, A. Sriwichian, W. Suebjaksing, P. Sukklad, T. Suttana, A. Tangsirira, O. Thangpet, W. Tiyanon, Y. Vorasettakarnkij, T. Wisaratapong, W. Wongtheptien, A. Wutthimanop, S. Yawila, A. Oto, A. Altun, I. Ozdogru, K. Ozdemir, O. Yilmaz, A. Aydinlar, M.B. Yilmaz, E. Yeter, Z. Ongen, M. Cayli, H. Pekdemir, M. Ozdemir, M. Sucu, T. Sayin, M. Demir, H. Yorgun, M. Ersanli, E. Okuyan, D. Aras, H. Abdelrahman, O. Aktas, D. Alpay, F. Aras, M.F. Bireciklioglu, S. Budeyri, M. Buyukpapuc, S. Caliskan, M. Esen, M.A. Felekoglu, D. Genc, B. Ikitimur, E.B. Karaayvaz, S. Kılıç Karataş, S. Okutucu, E. Ozcelik, A. Quisi, H. Sag, L. Sahiner, B.Y. Sayin, T. Seker, D. Uzun Alkan, E. Yildirim, R. Yildirim, F. Yilmaz, V. Yuksekdag, H.L. Luciardi, N. Vensentini, A.C. Ingaramo, G.A. Sambadaro, V. Fernandez Caputi, S.G. Berman, P. Dragotto, A.J. Kleiban, N. Centurion, G. Giacomi, R.A. Ahuad Guerrero, D. Conde, G. Zapata, L.A. Di Paola, J.L. Ramos, R.D. Dran, J. Egido, A.A. Fernandez, M.J. Fosco, S. Sassone, V.A. Sinisi, L.R. Cartasegna, M.A. Berli, O.A. Gomez Vilamajo, F. Ferroni, E.D. Alaguibe, A. Alvarez D'Amelio, C. Arabetti, L. Arias, J.A. Belardi, L. Bergesio, F. Berli, M. Berli, S. Borchowiec, C. Buzzetti, R. Cabrini, V. Campisi, A.L. Cappi, R. Carrizo, F. Colombo Berra, J.P. Costabel, O.J.A. Costamagna, A.A. Damonte, I.N. De Urquiza, F. Diez, M.F. Edén, M. Fanuele, F. Fernandez Voena, M. Foa Torres, C. Funosas, M.P. Giacomi, C.H. Gimenez, E.P. Gurfinkel, M. de L.M. Had, V. Hansen, A.D. Hrabar, M. Ingratta, A. Lopez, G. Maehara, L. Maffei, A. Martinelli, C. Martinelli, J. Matkovich, B. Mautner, A. Meirino, R. Munguia, A. Navarro, V. Novas, G. Perez Prados, J. Pontoriero, R.N. Potito, C. Ricotti, M.A. Rodriguez, F. Rolandi, M.E. Said Palladino, M. Salinger, L.S. Sanziani, P.O. Schygiel, A. Sossich, J.F. Tinto, L. Tonelli, A.L. Tufare, M. Vallejo, M.E. Yunis, M. Zillo, F.J. Zurbrigk, A.C.P. Barretto, D.C. Sobral Filho, J. Jaber, D. Armaganijan, J. Faria Neto, A. Steffens, W. Kunz Sebba Barroso de Souza, J.D. de Souza Neto, J.M. Ribeiro, M. Silveira Teixeira, P.R. Ferreira Rossi, L. Pires, D. Moreira, J.C. Moura Jorge, A. Menezes Lorga Filho, L.C. Bodanese, M. Westerlund Montera, C.H. Del Carlo, T. Da Rocha Rodrigues, F.A. Alves da Costa, A. Lopes, R. Lopes, G.R. Araújo, E.R. Fernandes Manenti, J.F. Kerr Saraiva, J.C. Ferreira Braga, A. Negri, L. Souto, C. Moncada, D. Bertolim Precoma, F. Roquette, G. Reis, R.A. Ramos Filho, E. Lanna Figueiredo, R. Vieira Botelho, C. Munhoz da Fontoura Tavares, C.R. Costantini Frack, J. Abdalla Saad, H.C. Finimundi, C. Pisani, D. Chemello, M. Pereira Martins, C.C. Broilo França, F. Alban, G.B. Aranha Rosito, J.B. de Moura Xavier Moraes Junior, R.T. Tumelero, L. Nigro Maia, R. Simões de Almeida, N.C. do Carmo Borges, L.G. Gomes Ferreira, P. Agliardi, J. Alves de Oliveira Gomes, V. Araujo, M. Arruda Nakazone, T. Barbosa, S. Barroso, E. Belisario Falchetto, H. Bellotti Lopes, M.A. Benez Teixeira Lemos, G. Biazus, L. Borges Queiroz, F.E. Camazzola, M. Caporale, S. Cardoso Boscato, F. Chieza, M.O. Chokr, R. Clemente Mingireanov, N. Codonho Góes, C. Correa, M. Costa, C. Costantini Ortiz, L.S. da Silva, F. da Silva Paulitsch, J.A. da Silveira, E. Daros, G.R. de Araújo, M.I. Del Monaco, C. Dias, M.A. Dias, A.P. Drummond Wainstein, P. Ely Pizzato, D.C. Esteves, P. Fabri, T. Félix Lorenzato Fonseca, E. Fernandes, C. Fonseca, C.R. Frack Costantini, R. Franchin Ferraz, F. Freire, P. Gottardo, D. Guanaes, S. Guizzardi, E. Hettwer Magedanz, F. Igansi, F. Jannuzzi, G. Junior, D. Komar, E.G. Lino, D. Lopes, O. Lourenço da Silva Júnior, E. Lustosa, A.P. Macagnan, M.C. Marinho, M. Mazzoni, G. Melo, L. Mortari, O.M.C.C. Mouco, C. Nanzer Vital, C. Ormundo, S. Oss Emmer, E. Palmegiani, R. Pavani, L. Pereira, V.L. Pereira, R. Perreira, S. Poletti, S.C. Quaia Fortunato, C. Queirantes, N. Ramos Pereira, R.L. Rech, S. Ribeiro, A. Rodrigues, H. Roesch, T. Ruaro Reichert, D. Santos, I. Santos, M. Santos, M.V. Seroqui, S. Silva, L. Soares, L. Spolaor, C. Stoll, N. Toazza Duda, L. Trama, B. Unterkircher, M.V. Valois, T. Vargas, T. Viana, C. Vicente, L. Vidal Armaganijan, R. Vieira Homem, L.G. Vieira Torres, L. Vila Boas, F. Villaça Guimarães Filho, R. Corbalan, G. Eggers, C. Bugueño Gutiérrez, G. Arriagada, S. Potthoff Cardenas, B.A.J. Stockins Fernandez, C. Conejeros, C. Houzvic, P. Marin Cuevas, H. Montecinos, A. Forero, F. Lanas, M. Larico Gómez, G. Charme Vilches, C. Rey, C. Astudillo, J. Aguilar, Y. Campisto, C. Lara, E. Molina, J. Munoz Oyarzon, V. Olguin, M. Vergara, C. Villan, C.J. Sánchez Díaz, J. Illescas Diaz, R. Leal Cantú, M.G. Ramos Zavala, R. Cabrera Jardines, N. Espinola Zavaleta, S. Villarreal Umaña, E. López Rosas, G. Llamas Esperón, G. Pozas, E. Cardona Muñoz, N. Matadamas Hernández, A. Leyva Rendón, N. García Hernández, M. de los Ríos Ibarra, L. Virgen Carrillo, D. López Villezca, C. Hernández Herrera, J.J. López Prieto, R. Gaona Rodríguez, E. Villeda Espinosa, D. Flores Martínez, J. Velasco Barcena, R. Yong, I. Rodríguez Briones, J.L. Leiva Pons, H. Álvarez López, R. Olvera Ruiz, C. Díaz de la Vega, C. Cantú Brito, E. Chuquiure Valenzuela, R. Reyes-Sanchez, A. Bazzoni Ruiz, O. Nandayapa Flores, M. Benavides Gonzalez, R. Arriaga Nava, J.D. Morales Cerda, O. Fierro Fierro, P. Fajardo Campos, T.A.A. Alfaro, S. Altamirano Bellorin, R. 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Robiro Robiro, M. Roca, C. Roca Saumell, C. Rodrigo, E. Rodriguez, M. Rodriguez Garcia, S. Saez Jimenez, P. Sanchez Calderon, L. Sanchez Mendez, S. Sanchez Parra, C. Santolaya, M.R. Senan Sanz, A. Seoane Blanco, E. Serralvo, N. Sierra, C. Simon Valero, J. Sorribes Lopez, M. Teixido Fontanillas, M. Terns Riera, G. Tobajas, C. Torres, J. Torres Marques, M. Ubeda Pastor, M. Rosenqvist, A. Wirdby, J. Linden, K. Henriksson, M. Elmersson, A. Egilsson, U. Börjesson, G. Svärd, B. Liu, A. Lindh, L.-B. Olsson, M. Gustavsson, Lars Andersson, Lisbeth Andersson, L. Benson, C. Bothin, A. Hajimirsadeghi, K. Kadir, M. Ericsson, A. Ohlsson, H. Lindvall, P. Svensson, K. Thorne, H. Handel, P. Platonov, B. Eriksson, I. Timberg, K. Romberg, M. Crisby, J.-E. Karlsson, S.A. Jensen, A. Andersson, L. Malmqvist, B. Martinsson, F. Bernsten, J. Engdahl, J. Thulin, A. Hot-Bjelac, P. Stalby, H. Aaröe, E. Ahbeck, H. Ahlmark, F. Al-Khalili, G. Bonkowski, S. Dzeletovic, A.-B. Ekstrand, G.-B. Eriksson, K. Floren, C. Grässjö, S. Hahn, P. Jaensson, B. Jansson, J.-H. Jansson, R.-M. Kangert, A. Koch, D. Kusiak, A. Lettenström, A. Lindberg, C.-J. Lindholm, A. Mannermyr, K. Mansson, M. Millborg, C. Nilsson, A.-M. Ohlin, A. Olofsson, A. Osberg, A. Pedersen, K. Risbecker, K. Rosenberg, J. Samuelsson, M. Shayesteh, K. Skoglund, M. Stjernberg, C. Thorsen, J. Steffel, J.H. Beer, J. Debrunner, D. Amstutz, J. Bruegger, G. Elise, A. Grau, A. Guinand, I. Henriette, E. Saga, S. Winnik, A. Parkhomenko, I. Rudyk, V. Tseluyko, O. Karpenko, S. Zhurba, I. Kraiz, I. Kupnovytska, N. Serediuk, Y. Mostovoy, O. Ushakov, O. Koval, I. Kovalskyi, Y. Svyshchenko, O. Sychov, M. Stanislavchuk, O. Kraydashenko, A. Yagensky, S. Tykhonova, I. Fushtey, R. Belegai, G. Berko, L. Burdeuna, O. Chabanna, I. Daniuk, A. Ivanov, E. Kamenska, P. Kaplan, O. Khyzhnyak, S. Kizim, O. Matova, O. Medentseva, V. Mochonyi, M. Mospan, V. Nemtsova, T. Ovdiienko, O. Palamarchuk, M. Pavelko, R. Petrovskyy, D. Plevak, O. Proshak, S. Pyvovar, L. Rasputina, O. Romanenko, O. Romanova, A. Sapatyi, O. Shumakov, R. Stets, L. Todoriuk, V. Varenov, D. Fitzmaurice, N. Chauhan, D. Goodwin, P. Saunders, R. Evans, J. Leese, P.S. Jhittay, A. Ross, M.S. Kainth, G. Pickavance, J. McDonnell, A. Williams, T. Gooding, H. Wagner, S. Suryani, A. Singal, S. Sircar, R. Bilas, P. Hutchinson, A. Wakeman, M. Stokes, N. Paul, M. Aziz, C. Ramesh, P. Wilson, S. Franklin, S. Fairhead, J. Thompson, V. St Joseph, G. Taylor, D. Tragen, D. Seamark, C. Paul, M. Richardson, A. Jefferies, H. Sharp, H. Jones, C. Giles, M. Page, O. Oginni, J. Aldegather, S. Wetherwell, W. Lumb, P. Evans, F. Scouller, N. Macey, Y. Stipp, R. West, S. Thurston, P. Wadeson, J. Matthews, P. Pandya, A. Gallagher, T. Railton, B. Sinha, D. Russell, J.A. Davies, P. Ainsworth, C.P. Jones, P. Weeks, J. Eden, D. Kernick, W. Murdoch, L. Lumley, R.P. Patel, S.W. Wong, M. Saigol, K. Ladha, K. Douglas, D.F. Cumberlidge, C. Bradshaw, G. Van Zon, K.P. Jones, M.J. Thomas, E. Watson, B. Sarai, N. Ahmad, W. Willcock, J. Cairns, S. Sathananthan, N. de Kare-Silver, A. Gilliland, E. Strieder, A. Howitt, B. Vishwanathan, N. Bird, D. Gray, M. Clark, J. Bisatt, J. Litchfield, E. Fisher, T. Fooks, A.R. Kelsall, E. Alborough, J. Wakeling, M. Parfitt, K. Milne, S. Rogers, R. Priyadharshan, J.L. Oliver, E. Davies, S. Abushal, M. Jacobs, C. Hutton, N.I. Walls, R. Thompson, C. Chigbo, S.M.A. Zaidi, M. Howard, K.C. Butter, S. Barrow, H. Little, I.U. Haq, L. Gibbons, S. Glencross, A.J. McLeod, K. Poland, C. Mulholland, A. Warke, P. Conn, G. Burns, R.N. Smith, S. Lowe, R. Kamath, H.S. Dau, J. Webster, I. Hodgins, S. Vercoe, P.C. Roome, H. Pinnock, J.R.A. Patel, A. Ali, N. Hart, R. Davies, E. Stuart, C.A. Neden, M. Danielsen, R. Heath, P. Sharma, S. Galloway, C. Hawkins, R. Oliver, M. Aylward, S. Mannion, M. Braddick, D. Edwards, A.C. Rothwell, A. Sabir, F. Choudhary, S. Khalaque, A. Wilson, S. Peters, W. Coulson, N. Roberts, A. Heer, S. Coates, B. Ward, D. Jackson, S. Walton, D. Shepherd, M. Sterry, T. Wong, M. Boon, R. Bunney, R. Haria-Shah, R.T. Baron, S. Davies, T. Schatzberger, N. Hargreaves, T. Stephenson, H. Choi, R. Batson, L. Lucraft, T. Myhill, S. Estifano, D. Geatch, J. Wilkinson, R. Veale, K. Forshaw, T. Davies, K. Zaman, P. Vinson, C. Liley, M. Bandrapalli, P. McGinty, R. Wastling, P. McEleny, A. Beattie, P. Cooke, M. Wong, J. Gunasegaram, M. Pugsley, S. Ahmad, C. A'Court, J. Ayers, J. Bennett, S. Cartwright, S. Dobson, C. Dooldeniya, A. Flynn, R. Fox, J. Goram, A. Halpin, A. Hay, P. Jacobs, L. Jeffers, L. Lomax, I. Munro, R. Muvva, M. Nadaph, K. Powell, S. Randfield, D. Redpath, R. Reed, M. Rickenbach, G. Rogers, P.B. Saunders, C. Seamark, J. Shewring, P. Simmons, H. Simper, H. Stoddart, A. Sword, N. Thomas, A. Thomson, H. Gibbs, A. Blenkhorn, B. Singh, W. Van Gaal, W. Abhayaratna, R. Lehman, P. Roberts-Thomson, J. Kilian, D. Coulshed, A. Catanchin, D. Colquhoun, H. Kiat, D. Eccleston, J. French, L. Zimmett, B. Ayres, T. Phan, P. Blombery, D. Crimmins, D. O'Donnell, A. Choi, P. Astridge, M. Arstall, N. Jepson, M. Binnekamp, A. Lee, J. Rogers, G. Starmer, P. Carroll, J. Faunt, A. Aggarwala, L. Barry, C. Batta, R. Beveridge, A. Black, M. Bonner, J. Boys, E. Buckley, M. Campo, L. Carlton, A. Connelly, B. Conway, D. Cresp, H. Dimitri, S. Dixon, M. Dolman, M. Duroux, M. Eskandari, R. Eslick, A. Ferreira-Jardim, T. Fetahovic, D. Fitzpatrick, R. Geraghty, J. Gibbs, T. Grabek, M.H. Modi, K. Hayes, M.P. Hegde, L. Hesketh, B. Hoffmann, B. Jacobson, K. Johnson, C. Juergens, I. Kassam, V. Lawlor, M. Lehman, S. Lehman, D. Leung, S. Mackay, M. MacKenzie, C. McCarthy, C. McIntosh, L. McKeon, H. Morrison, C. Mussap, J.-D. Myers, V. Nagalingam, G. Oldfield, V. O'May, J. Palmer, L. Parsons, K. Patching, T. Patching, V. Paul, M. Plotz, S. Preston, H. Rashad, M. Ratcliffe, S. Raynes, J. Rose, L. Sanders, M. Seremetkoska, H. Setio, S. Shone, P. Shrestha, C. Singh, C. Singleton, N. Stoyanov, S. Sutcliffe, K. Swaraj, J. Tarrant, S. Thompson, I.M. Tsay, M. Vorster, A. Waldman, L. Wallis, E. Wilford, K. Wong, S.J. Connolly, A. Spyropoulos, J. Eikelboom, R. Luton, M. Gupta, A.S. Pandey, S. Cheung, R. Leader, P. Beaudry, F. Ayala-Paredes, J. Berlingieri, J. Heath, G. Poirier, M. Du Preez, R. Nadeau, G. Dresser, R. Dhillon, T. Hruczkowski, B. Schweitzer, B. Coutu, P. Angaran, P. MacDonald, S. Vizel, S. Fikry, R. Parkash, A. Lavoie, J. Cha, B. Ramjattan, J. Bonet, K. Ahmad, L. Aro, T. Aves, K. Beaudry, C. Bergeron, J. Bigcanoe, N. Bignell, L. Breakwell, E. Burke, L. Carroll, B. Clarke, T. Cleveland, S. Daheb, P. Dehghani, I. Denis, Z. Djaidani, P. Dorian, S. Douglass, J. Dunnigan, A. Ewert, D. Farquhar, A. Fearon, L. Ferleyko, D. Fournier, B. Fox, M.-C. Grenier, W. Gulliver, K. Haveman, C. Hines, K. Hines, A.M. Jackson, C. Jean, G. Jethoo, R. Kahlon, S. Kelly, R. Kim, V. Korley, J. Kornder, L. Kwan, J. Largy, C. Lewis, S. Lewis, I. Mangat, R. Moor, J. Navratil, I. Neas, J. Otis, R. Otis, M. Pandey, F. Petrie, A. Pinter, M. Raines, P. Roberts, M. Robinson, G. Sas, S. Schulman, L. Snell, S. Spearson, J. Stevenson, T. Trahey, S. Wong, D. Wright, H. Ragy, A. Abd El-Aziz, S.K. Abou Seif, M.G. El Din, S. El Etriby, A. Elbahry, A. El-Etreby, M. Elkhadem, A. Katta, T. Khairy, A. Mowafy, M. Nawar, A. Ohanissian, A. Reda, M. Reda, H. Salem, N. Sami, S. Samir, M. Setiha, M. Sobhy, A. Soliman, N. Taha, M. Tawfik, E. Zaatout, D. Kettles, J. Bayat, H. Siebert, A. Horak, Y. Kelfkens, R. Garda, T. Pillay, M. Guerra, L. van Zyl, H. Theron, A. Murray, R. Louw, D. Greyling, P. Mntla, V. Ueckermann, R. Loghdey, S. Ismail, F. Ahmed, J. Engelbrecht, A. Ramdass, S. Maharajh, W. Oosthuysen, G. Angel, C. Bester, M. Booysen, C. Boshoff, C. Cannon, S. Cassimjee, C. Chami, G. Conway, A. Davids, L. de Meyer, G. Du Plessis, T. Ellis, L. Henley, M. Karsten, E. Loyd, J. Marks, L. Mavhusa, M. Mostert, A. Page, L. Rikhotso, M. Salie, J. Sasto, F. Shaik, A. Skein, L. Smith, G. Tarr, T. Tau, F. van Zyl, W. Al Mahmeed, G. Yousef, A. Agrawal, M. Nathani, M. Ibrahim, E.M. Esheiba, R. Singh, A. Naguib, M. Abu-Mahfouz, M. Al Omairi, A. Al Naeemi, R. Maruthanayagam, N. Bazargani, A. Wassef, R. Gupta, M. Khan, B. Subbaraman, A. Abdul, A. Al Mulla, S. El Bardisy, P. Haridas, S. Jadhav, K. Magdaluyo, M. Makdad, I. Maqsood, R. Mohamed, N. Sharma, R. Sharma, M. Thanzeel, S.Z. Goldhaber, R. Canosa, P. Rama, E. Blumberg, J. Garcia, P. Mullen, V. Wilson, A. Quick, K. Ferrick, W.M. Kutayli, M. Cox, M. Franco, S. Falkowski, R. Mendelson, M. Williams, S. Miller, S. Beach, A. Alfieri, T. Gutowski, I. Haque, R. Reddy, W. Ahmed, P. Delafontaine, D. Diercks, D. Theodoro, K. Remmel, M. Alberts, R. Ison, H. Noveck, P. Duffy, S. Pitta, D. Nishijima, C. Treasure, N. Asafu-Adjaye, K. Ball, M. Bartlett, M. Bentley, S. Bowers, A. Brown, A. Browne, J. Cameron-Watts, M. Canova, D. Cassidy, K. Cervellione, S. Congal, J. DePauw, A. Dickerson, M. Eley, L. Evans, S. Felpel, K. Ferdinand, D. Fielder, P. Gentry, A. Haideri, F. Hakimi, T. Harbour, E. Hartranft, B. Hawkins, M. Headlee, L. Henson, C. Herrick, T. Hicks, S. Jasinski, A. Jones, L. Jones, P. Jones, S. Karl, M. Keeling, J. Kerr, P. Knowles, J. Langdon, M. Lay, J.A. Lee, T. Lincoln, E. Malone, A. Merliss, D. Merritt, J. Minardo, B. Mooso, C. Orosco, V. Palumbo, M. Parker, T. Parrott, S. Paserchia, G. Pearl, J. Peterson, N. Pickelsimer, T. Purcell, J. Raynor, S. Raziano, C. Richard, T. Richardson, C. Robertson, A. Sage, T. Sanghera, P. Shaw, J. Shoemaker, K. Smith, B. Stephanie, A. Thatcher, H. Theobald, N. Thompson, L. Treasure, T. Tripti, C. Verdi, and V. Worthy
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Surgery ,RD1-811 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background: The Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. Methods and results: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012–2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P
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- 2018
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3. Global mortality variations in patients with heart failure: results from the International Congestive Heart Failure (INTER-CHF) prospective cohort study
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Dr Hisham Dokainish, MD, Koon Teo, PhD, Jun Zhu, MD, Ambuj Roy, MD, Khalid F AlHabib, MBBS, Ahmed ElSayed, MD, Lia Palileo-Villaneuva, MD, Patricio Lopez-Jaramillo, PhD, Kamilu Karaye, MD, Khalid Yusoff, MD, Andres Orlandini, MD, Karen Sliwa, PhD, Charles Mondo, MD, Fernando Lanas, MD, Dorairaj Prabhakaran, MD, Amr Badr, MD, Mohamed Elmaghawry, PhD, Albertino Damasceno, MD, Kemi Tibazarwa, MD, Emilie Belley-Cote, MD, Kumar Balasubramanian, MSc, Shofiqul Islam, MSc, Magdi H Yacoub, MD, Mark D Huffman, MD, Karen Harkness, PhD, Alex Grinvalds, BSc, Robert McKelvie, PhD, Shrikant I Bangdiwala, PhD, Salim Yusuf, DPhil, R. Campos, C. Chacón, G. Cursack, F. Diez, C. Escobar, C. Garcia, O. Gomez Vilamajo, M. Hominal, A. Ingaramo, G. Kucharczuk, M. Pelliza, A. Rojas, A. Villani, G. Zapata, P. Bourke, F. Lanas, L. Nahuelpan, C. Olivares, R. Riquelme, F. Ai, X. Bai, X. Chen, Y. Chen, M. Gao, C. Ge, Y. He, W. Huang, H. Jiang, T. Liang, X. Liang, Y. Liao, S. Liu, Y. Luo, L. Lu, S. Qin, G. Tan, H. Tan, T. Wang, X. Wang, F. Wei, F. Xiao, B. Zhang, T. Zheng, J.L. Accini Mendoza, M. Blanquicett Anaya, E. Gomez, D.I. Molina de Salazar, F. Quiroz, M.J. Rodríguez, M. Suarez Sotomayor, A. Torres Navas, M. Bravo León, L.A. Falconi Montalvo, M. Lopez Jaramillo, E. Peñaherrera Patiño, C. Perugachi, F. Trujillo Cruz, M. Elmaghawry, K. Wagdy, A.K. Bhardwaj, V. Chaturvedi, G. Krishna Gokhale, R. Gupta, R. Honnutagi, P. Joshi, S. Ladhani, P.C. Negi, A. Roy, N. Reddy, A. Abdullah, M.R. Abu Hassan, M. Balasinga, S. Kasim, W.Y. Tan, K. Yusoff, A. Damasceno, R. Banze, E. Calua, C. Novela, J. Chemane, A.A. Akintunde, V. Ansa, H. Gbadamosi, K.M. Karaye, A. Mbakwem, S. Mohammed, E. Nwafor, D. Ojji, T. Olunuga, B. Onwubere H. Sa'idu, E. Umuerri, J. Alcaraz, L. Palileo-Villanueva, E. Palomares, M. Roxas Timonera, A. Badr, S. Alghamdi, K. Alhabib, A. Almasood, S. Alsaif, A. Elasfar, A. Ghabashi, L. Mimish, F. Bester, D. Kelbe, E. Klug, K. Sliwa, K. Tibarzawa, O.E. Abdalla, M.E. Dimitri, H. Mustafa, O. Osman, A. Saad, and C. Mondo
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Public aspects of medicine ,RA1-1270 - Abstract
Background: Most data on mortality and prognostic factors in patients with heart failure come from North America and Europe, with little information from other regions. Here, in the International Congestive Heart Failure (INTER-CHF) study, we aimed to measure mortality at 1 year in patients with heart failure in Africa, China, India, the Middle East, southeast Asia and South America; we also explored demographic, clinical, and socioeconomic variables associated with mortality. Methods: We enrolled consecutive patients with heart failure (3695 [66%] clinic outpatients, 2105 [34%] hospital in patients) from 108 centres in six geographical regions. We recorded baseline demographic and clinical characteristics and followed up patients at 6 months and 1 year from enrolment to record symptoms, medications, and outcomes. Time to death was studied with Cox proportional hazards models adjusted for demographic and clinical variables, medications, socioeconomic variables, and region. We used the explained risk statistic to calculate the relative contribution of each level of adjustment to the risk of death. Findings: We enrolled 5823 patients within 1 year (with 98% follow-up). Overall mortality was 16·5%: highest in Africa (34%) and India (23%), intermediate in southeast Asia (15%), and lowest in China (7%), South America (9%), and the Middle East (9%). Regional differences persisted after multivariable adjustment. Independent predictors of mortality included cardiac variables (New York Heart Association Functional Class III or IV, previous admission for heart failure, and valve disease) and non-cardiac variables (body-mass index, chronic kidney disease, and chronic obstructive pulmonary disease). 46% of mortality risk was explained by multivariable modelling with these variables; however, the remainder was unexplained. Interpretation: Marked regional differences in mortality in patients with heart failure persisted after multivariable adjustment for cardiac and non-cardiac factors. Therefore, variations in mortality between regions could be the result of health-care infrastructure, quality and access, or environmental and genetic factors. Further studies in large, global cohorts are needed. Funding: The study was supported by Novartis.
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- 2017
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4. An open-source application software to determine the preconsolidation pressure of soils in incremental loading oedometer testing: pySigmaP
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Exneyder A. Montoya-Araque, A.J. Aparicio-Ortube, David G. Zapata-Medina, and Luis G. Arboleda-Monsalve
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Soil ,QA76.75-76.765 ,Oedometer testing ,Python 3 ,Open-source application software ,Computer software ,Preconsolidation pressure ,Software ,Computer Science Applications - Abstract
This paper presents pySigmaP, an open-source application software developed in Python 3 under the object-oriented paradigm to determine the preconsolidation pressure, σp′, of soils in incremental loading oedometer testing. pySigmaP was implemented with nine methods: Casagrande, Pacheco Silva, Butterfield, Oikawa, Becker et al., Morin, Onitsuka et al., Wang and Frost, and Boone. Analytical and numerical methods were employed to minimize numerical bias and scale dependency when performing graphical constructions for the determination of σp′. Procedure and numerical application of each method were also presented. pySigmaP provides a more objective and straightforward analysis to estimate σp′of a soil deposit using those nine widely accepted methods.
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- 2022
5. Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study
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José M. Sempere, Bernat Soria, Mariano García-Arranz, Miriam López-Parra, Pablo Monedero, Bárbara Soria-Juan, José Luis Del-Pozo, Miguel Vicente Sanchez-Hernandez, María Eugenia Fernández-Santos, José Eugenio Guerrero, Víctor Sagredo, Fermín Sánchez-Guijo, Carmen Mata-Martínez, Etelvina Andreu, Damián García-Olmo, Agustín G. Zapata, Luis Hernandez-Blasco, Francisco Fernández-Avilés, José Manuel Alvarez-Avello, Enrique J. Andreu, César Pérez-Calvo, Arnoldo Santos, José M. Moraleda, Felipe Prosper, UAM. Departamento de Cirugía, Universidad de Alicante. Departamento de Biotecnología, and Grupo de Inmunología, Biología Celular y del Desarrollo
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Gastrointestinal bleeding ,Medicina ,medicine.medical_treatment ,Cellular therapy ,Inmunología ,Mesenchymal stromal cells ,Enfermedades infecciosas ,01 natural sciences ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Tocilizumab ,Mechanical ventilation ,Interquartile range ,medicine ,030212 general & internal medicine ,0101 mathematics ,Adverse effect ,Case series ,lcsh:R5-920 ,Biología celular ,business.industry ,SARS-CoV-2 ,010102 general mathematics ,COVID-19 ,Lopinavir ,Hydroxychloroquine ,General Medicine ,Pneumonia ,medicine.disease ,chemistry ,Anesthesia ,business ,lcsh:Medicine (General) ,medicine.drug - Abstract
Background: Identification of effective treatments in severe cases of COVID-19 requiring mechanical ventilation represents an unmet medical need. Our aim was to determine whether the administration of adipose-tissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients. Methods: Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR- 1 day) after the first one. Two patients received a single dose and another patient received 3 doses. Median number of cells per dose was 0.98 × 106 (IQR 0.50 × 106) AT-MSC/kg of recipient's body weight. Potential adverse effects related to cell infusion and clinical outcome were assessed. Additional parameters analyzed included changes in imaging, analytical and inflammatory parameters. Findings: First dose of AT-MSC was administered at a median of 7 days (IQR 12 days) after mechanical ventilation. No adverse events were related to cell therapy. With a median follow-up of 16 days (IQR 9 days) after the first dose, clinical improvement was observed in nine patients (70%). Seven patients were extubated and discharged from ICU while four patients remained intubated (two with an improvement in their ventilatory and radiological parameters and two in stable condition). Two patients died (one due to massive gastrointestinal bleeding unrelated to MSC therapy). Treatment with AT-MSC was followed by a decrease in inflammatory parameters (reduction in C-reactive protein, IL-6, ferritin, LDH and d-dimer) as well as an increase in lymphocytes, particularly in those patients with clinical improvement. Interpretation: Treatment with intravenous administration of AT-MSC in 13 severe COVID-19 pneumonia under mechanical ventilation in a small case series did not induce significant adverse events and was followed by clinical and biological improvement in most subjects. Funding: None. We would like to acknowledge the Instituto de Salud Carlos III (ISCIII) through the project “RD16/0011: Red de Terapia Celular”, from the sub-program RETICS, integrated in the “Plan Estatal de I+D+I 2013-2016” and co-financed by the European Regional Development Fund “A way to make Europe”, groups RD16/0011/0001, -/0002, -/005, -/0013, -/0015, -/0029), the Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Spain and AvanCell-CM (Red de Investigación de Terapia Celular de la Comunidad de Madrid, Spain), for supporting some personnel and networking activities.
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- 2020
6. Global mortality variations in patients with heart failure: results from the International Congestive Heart Failure (INTER-CHF) prospective cohort study
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T. Zheng, E. Calua, E. Nwafor, L.A. Falconi Montalvo, L. Nahuelpan, A. Villani, F. Wei, H. Tan, M. Gao, H. Mustafa, Prakash Chand Negi, Dike B. Ojji, Jun Zhu, X. Liang, Layth Mimish, F. Xiao, G. Cursack, X. Bai, M. Blanquicett Anaya, T. Wang, Osman Osman, Abdullah Ghabashi, VO Ansa, Taiwo Olunuga, Koon K. Teo, K. Tibarzawa, A. Ingaramo, W.Y. Tan, R. Honnutagi, J. Alcaraz, Andres Orlandini, Karen Sliwa, Célia Novela, Magdi H. Yacoub, A. Torres Navas, F. Trujillo Cruz, A. Badr, Sulaiman Ladhani, G. Krishna Gokhale, P. Bourke, Kamilu M. Karaye, E. Peñaherrera Patiño, Amam Mbakwem, Karen Harkness, C. Escobar, C. Olivares, N. Reddy, Shafiu Mohammed, Salim Yusuf, F. Quiroz, G. Tan, S. Liu, Abdelfatah Elasfar, T. Liang, X. Wang, Ambuj Roy, B. Zhang, Hisham Dokainish, B. Onwubere H. Sa'idu, M.R. Abu Hassan, F. Bester, M. Bravo León, M. Balasinga, F Lanas, F. Ai, Saleh AlGhamdi, M. Lopez Jaramillo, Charles Mondo, M. Roxas Timonera, D. Kelbe, O.E. Abdalla, Amr Badr, Vivek Chaturvedi, R. Banze, S. Qin, R Gupta, K.M. Karaye, A.K. Bhardwaj, E. Klug, Adeseye A Akintunde, Khalid F. AlHabib, M. Hominal, Y. Liao, Ahmed Saad, M.J. Rodríguez, M. Suarez Sotomayor, Fernando Lanas, H. Jiang, C. Garcia, L. Lu, X. Chen, G. Kucharczuk, Shrikant I. Bangdiwala, J.L. Accini Mendoza, K. Sliwa, Y. He, Lia Palileo-Villaneuva, H. Gbadamosi, Mark D. Huffman, Emilie P. Belley-Côté, C. Chacón, Shukri AlSaif, F. Diez, Patricio Lopez-Jaramillo, Akmaliza Abdullah, W. Huang, Ali Almasood, Kerolos Wagdy, C. Perugachi, Robert S. McKelvie, Kamaruzzaman bin Yusoff, E M Umuerri, A. Damasceno, C. Ge, Sazzli Kasim, Dorairaj Prabhakaran, M. Elmaghawry, Elieth Gomez, E. Palomares, Lia M. Palileo-Villanueva, Y. Chen, C. Mondo, G. Zapata, Alex Grinvalds, A. Rojas, M. Pelliza, D.I. Molina de Salazar, O. Gomez Vilamajo, Prashant P. Joshi, R. Riquelme, Mohamed ElMaghawry, Kumar Balasubramanian, A. Roy, Albertino Damasceno, M.E. Dimitri, J. Chemane, Shofiqul Islam, KF AlHabib, Ahmed Elsayed, Y. Luo, Kemi Tibazarwa, Khalid Yusoff, and R. Campos
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COUNTRIES ,AFRICA ,Male ,ASCEND-HF ,030204 cardiovascular system & hematology ,Global Health ,03 medical and health sciences ,0302 clinical medicine ,CLINICAL CHARACTERISTICS ,Risk Factors ,ECONOMIC BURDEN ,MANAGEMENT ,medicine ,Global health ,Humans ,In patient ,Prospective Studies ,030212 general & internal medicine ,Mortality ,Prospective cohort study ,Socioeconomic status ,Public, Environmental & Occupational Health ,Aged ,Heart Failure ,OUTCOMES ,Science & Technology ,Models, Statistical ,Proportional hazards model ,business.industry ,lcsh:Public aspects of medicine ,Global ,lcsh:RA1-1270 ,General Medicine ,Middle Aged ,medicine.disease ,INTER-CHF Investigators ,Hospitalization ,INTER-CHF ,Socioeconomic Factors ,REGISTRY ,Heart failure ,TRIAL ,Female ,Risk of death ,business ,Life Sciences & Biomedicine ,REDUCED EJECTION FRACTION ,Kidney disease ,Demography - Abstract
8 p., Background Most data on mortality and prognostic factors in patients with heart failure come from North America and Europe, with little information from other regions. Here, in the International Congestive Heart Failure (INTERCHF) study, we aimed to measure mortality at 1 year in patients with heart failure in Africa, China, India, the Middle East, southeast Asia and South America; we also explored demographic, clinical, and socioeconomic variables associated with mortality. Methods We enrolled consecutive patients with heart failure (3695 [66%] clinic outpatients, 2105 [34%] hospital in patients) from 108 centres in six geographical regions. We recorded baseline demographic and clinical characteristics and followed up patients at 6 months and 1 year from enrolment to record symptoms, medications, and outcomes. Time to death was studied with Cox proportional hazards models adjusted for demographic and clinical variables, medications, socioeconomic variables, and region. We used the explained risk statistic to calculate the relative contribution of each level of adjustment to the risk of death. Findings We enrolled 5823 patients within 1 year (with 98% follow-up). Overall mortality was 16·5%: highest in Africa (34%) and India (23%), intermediate in southeast Asia (15%), and lowest in China (7%), South America (9%), and the Middle East (9%). Regional differences persisted after multivariable adjustment. Independent predictors of mortality included cardiac variables (New York Heart Association Functional Class III or IV, previous admission for heart failure, and valve disease) and non-cardiac variables (body-mass index, chronic kidney disease, and chronic obstructive pulmonary disease). 46% of mortality risk was explained by multivariable modelling with these variables; however, the remainder was unexplained. Interpretation Marked regional differences in mortality in patients with heart failure persisted after multivariable adjustment for cardiac and non-cardiac factors. Therefore, variations in mortality between regions could be the result of health-care infrastructure, quality and access, or environmental and genetic factors. Further studies in large, global cohorts are needed. Funding The study was supported by Novartis.
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- 2017
7. Effects of Glucocorticoids on the Developing Thymus
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Angeles Vicente, Alberto Varas, Rosa Sacedón, Agustín G. Zapata, Carmen Hernández-López, Juan J. Muñoz, and Eva Jiménez
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endocrine system ,Stromal cell ,Lymphocyte ,Biology ,Thymocyte ,medicine.anatomical_structure ,Glucocorticoid receptor ,Immune system ,health services administration ,Immunology ,polycyclic compounds ,medicine ,sense organs ,Progenitor cell ,hormones, hormone substitutes, and hormone antagonists ,Homeostasis ,Hormone - Abstract
Involvement of glucocorticoids (GCs) in the homeostasis of immune system has been extensively studied. However, numerous questions remain unresolved, including the role played by these hormones in the physiology of thymus gland, a central, key organ involved in T-cell maturation. In this study, we review the available information on the relationships between GCs and thymus gland with special emphasis on glucocorticoid receptor (GR) expression in the organ, the presumptive endogenous production of GCs in the thymus gland, and the role played by GCs in the development of thymocytes, thymic epithelial cells, and thymic dendritic cells (DCs). Our review concludes (1) the lack of correlation between GR expression on thymocyte subsets and sensitivity to GCs; (2) however, GCs could affect the maturation of lymphocyte progenitors which colonize the thymic primordium during early ontogeny; (3) furthermore, GCs affect also the development of main thymic stromal components, including epithelium and DCs; (4) the involvement of GCs in the determination of intrathymic T-cell repertoire is an important matter of discussion although recent data support a lack of effects of GCs on those processes.
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- 2007
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8. Cells and Tissues of the Immune System of Fish
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Alberto Varas, Akira Chibá, and Agustín G. Zapata
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Head Kidney ,Pathology ,medicine.medical_specialty ,Spleen ,Biology ,Plasma cell ,biology.organism_classification ,Molecular biology ,Epithelium ,Staining ,medicine.anatomical_structure ,Immune system ,biology.animal ,medicine ,Carp ,Hagfish - Abstract
This chapter focuses on the cell and tissues of the immune system of fish. In teleosts, three types of granulocytes—heterophils, acidophils, and basophils—have been reported. There is enormous variation within the teleosts in both relative abundance and staining reaction of the granulocytes. In the carp, Cyprinus carpio, all three types of granulocytes are found in the blood. Among them, the heterophils and basophils are the least numerous and constitute 1% of the total eukocyte count. The acidophilic granulocytes are rather abundant and constitute 8% of the total leukocyte count. The acidophilic granules are peroxidase positive and contain round or irregular granules with heterogeneous contents. Migrating leukocytes in the basal mucosa and submucosa, as well as in the epithelium but not lymphoid aggregates, have been detected in the hagfish intestine. In the stingray, Dasyatis akajei , meningeal lymphohemopoietic masses appear predominantly in the telencephalon, diencephalon, and mesencephalon. Antigen-binding cells and antibody-producing cells have been found in the lymphohemopoietic tissue of the teleost kidney Recently, a higher number of Ig-positive cells have been found in the head kidney than in the spleen. They occur as scattered cells or forming small pyroninophilic cell clusters, especially after antigenic stimulation. It has been observed that that the cells of the pyroninophilic clusters corresponded to the plasma cell lineage with Ig-producing capacity and to the large lymphoid type plasma cells that gradually differentiate in these cell clusters.
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- 1996
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9. Contributors
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Douglas P. Anderson, Akira Chibá, Trevor P.T. Evelyn, Stephen L. Kaattari, Margaret J. Manning, Teruyuki Nakanishi, Jon D. Piganelli, Carl B. Schreck, C.J. Secombes, Mary F. Tatner, Alberto Varas, Tomoki Yano, and Agustín G. Zapata
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- 1996
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10. On the Approximation of Functions in Inductive Limits
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G. Zapata
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Discrete mathematics ,Polynomial ,Range (mathematics) ,Pure mathematics ,Partition of unity ,Simple (abstract algebra) ,media_common.quotation_subject ,Countable set ,Differentiable function ,Infinity ,Manifold ,media_common ,Mathematics - Abstract
Publisher Summary This chapter describes the approximation of functions in inductive limits. Tomake a unified approach to the approximation problem and obtain useful results, it is assumed that the algebra A ⊂ (X; ℝ) is separating and does not vanish at any point on X. This assumption provides an important partition of unity technique. Hence, the approximation problem reduces to the compact open case and the approximation on manifolds reduces to the approximation on open subsets of ℝ n . The above reductions, together with a vector valued polynomial approximation result, allows to obtain, in a simple way, a description of dense polynomial algebras related to Stone and Nachbin conditions. In the theorems concerning the approximation of differentiable functions on manifolds, the usual restrictions on the manifold, such as being pure and countable at infinity, are removed, thus enlarging their range of applicability.
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- 1982
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11. Analytical formulation for the study of the effect of shear deformations on beam-columns and piles: Engesser and Haringx theories
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Carlos A. Vega-Posada, David G. Zapata-Medina, and Edwin F. Garcia Aristizabal
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Beam-columns ,Piles ,Engesser method ,Haringx method ,Inhomogeneous soil ,Shear deformation ,Engineering geology. Rock mechanics. Soil mechanics. Underground construction ,TA703-712 - Abstract
This paper presents a novel analytical formulation to study the impact of shear deformations on beam-columns and piles by means of the Timoshenko-Engesser’s and Timoshenko-Haringx’s theories. The proposed solution enables the analysis of lateral deformation or buckling, while considering the effect of shear deformations. It offers the flexibility to i) incorporate different boundary conditions at the ends of the element (e.g., semi-rigid connections and lateral transverse springs) and ii) consider an inhomogeneous elastic foundation. When certain variables are disregarded, the proposed GDE can capture particular cases of GDEs found in the literature for beam-columns and piles. Examples are provided to demonstrate the simplicity and practicality of the proposed method, and its accuracy is validated against available analytical or numerical methods. The influence of the shear effects, as computed from Engesser’s and Haringx’s methods, on the lateral and buckling responses of beam-column and pile elements is discussed.
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- 2024
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12. Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study
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Fermín Sánchez-Guijo, Mariano García-Arranz, Miriam López-Parra, Pablo Monedero, Carmen Mata-Martínez, Arnoldo Santos, Víctor Sagredo, José-Manuel Álvarez-Avello, José Eugenio Guerrero, César Pérez-Calvo, Miguel-Vicente Sánchez-Hernández, José Luis Del-Pozo, Enrique J. Andreu, María-Eugenia Fernández-Santos, Barbara Soria-Juan, Luis M. Hernández-Blasco, Etelvina Andreu, José M. Sempere, Agustín G. Zapata, José M. Moraleda, Bernat Soria, Francisco Fernández-Avilés, Damián García-Olmo, and Felipe Prósper
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COVID-19 ,SARS-CoV-2 ,Pneumonia ,Mechanical ventilation ,Mesenchymal stromal cells ,Cellular therapy ,Medicine (General) ,R5-920 - Abstract
Background: Identification of effective treatments in severe cases of COVID-19 requiring mechanical ventilation represents an unmet medical need. Our aim was to determine whether the administration of adipose-tissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients. Methods: Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR- 1 day) after the first one. Two patients received a single dose and another patient received 3 doses. Median number of cells per dose was 0.98 × 106 (IQR 0.50 × 106) AT-MSC/kg of recipient's body weight. Potential adverse effects related to cell infusion and clinical outcome were assessed. Additional parameters analyzed included changes in imaging, analytical and inflammatory parameters. Findings: First dose of AT-MSC was administered at a median of 7 days (IQR 12 days) after mechanical ventilation. No adverse events were related to cell therapy. With a median follow-up of 16 days (IQR 9 days) after the first dose, clinical improvement was observed in nine patients (70%). Seven patients were extubated and discharged from ICU while four patients remained intubated (two with an improvement in their ventilatory and radiological parameters and two in stable condition). Two patients died (one due to massive gastrointestinal bleeding unrelated to MSC therapy). Treatment with AT-MSC was followed by a decrease in inflammatory parameters (reduction in C-reactive protein, IL-6, ferritin, LDH and d-dimer) as well as an increase in lymphocytes, particularly in those patients with clinical improvement. Interpretation: Treatment with intravenous administration of AT-MSC in 13 severe COVID-19 pneumonia under mechanical ventilation in a small case series did not induce significant adverse events and was followed by clinical and biological improvement in most subjects. Funding: None.
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- 2020
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13. Widespread presence of metallic compounds and organic contaminants across Pacific coral reef fish.
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Wejieme N, Vigliola L, Parravicini V, Sellanes J, Wafo E, Zapata-Hernandez G, Bustamante P, and Letourneur Y
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- Animals, Pacific Ocean, Metals analysis, Polychlorinated Biphenyls analysis, Pacific Islands, Trace Elements analysis, Coral Reefs, Water Pollutants, Chemical analysis, Environmental Monitoring, Fishes
- Abstract
Coral reef fishes represent an invaluable source of macro- and micro-nutrients for tropical coastal populations. However, several potentially toxic compounds may jeopardize their contribution to food security. Concentrations of metallic compounds and trace elements (MTEs), and persistent organic pollutants (POPs, including pesticides and polychlorobiphenyls PCBs), totalizing 36 contaminants, were measured in coral reef fish from several Pacific islands. The objective of this study was to describe the spatial distribution of these compounds and contaminants in order to identify potential variables explaining their distribution at a Pacific-wide scale. To achieve this, we applied Boosted Regression Trees to model species-specific and community-level contaminant and inorganic compound concentrations at the scale of the tropical Pacific Ocean. Overall, using 15 easily accessible explanatory variables, we successfully explained between 60 and 87 % of the global variation, with fish body size being the most important correlate of MTEs and POPs concentrations in reef fish. Our modeling approach allowed us to estimate and map the distribution of the community-level concentration of 19 contaminants and inorganic compounds at the scale of the equatorial and south Pacific Ocean. Spatial patterns varied significantly depending on the compound, with modeled quantities per 100 g of fish flesh generally being higher in the central and southwest Pacific than in the eastern part of the basin. These patterns were influenced by a combination of biological, environmental, anthropogenic and biogeographical variables. Overall, this approach represents an important step toward the estimation of concentrations of the main compounds on the basis of species identity and fishing location. Our results enhance our understanding of the extent of contamination in the Pacific while underscoring the urgent need for long-term and large-scale spatial monitoring of diverse compounds in this region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial and technical interest or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
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- 2025
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14. Heart Failure at Admission Complicating ST-Elevation Myocardial Infarction in a Middle-Income Country. Experience of the ARGEN-IAM-ST Registry.
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Zoni CR, D'Imperio H, Zapata G, Charask A, Macín SM, Castillo Costa Y, Ravi Y, Gagliardi J, and Perna ER
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- Humans, Female, Prognosis, Registries, Risk Factors, ST Elevation Myocardial Infarction complications, ST Elevation Myocardial Infarction diagnosis, ST Elevation Myocardial Infarction epidemiology, Heart Failure epidemiology, Heart Failure therapy, Heart Failure etiology, Hypertension
- Abstract
Despite advances in the management of ST-elevation myocardial infarction (STEMI), when associated with heart failure (HF) its prognosis remains ominous. This study assessed the differences in admission and mortality of HF complicating STEMI at admission (HFad) in a middle-income country. Data from the National Registry of STEMI of Argentina (ARGEN-IAM-ST) from January 1, 2016, to September 30, 2020, were analyzed. HFad was defined by the identification of Killip/Kimball ≥2 at admission. About 3174 patients were analyzed (22.3% had HFad). Patients with HFad were older, more often women, hypertensive, and diabetic. Received less reperfusion (87.6% vs 92.6%, P < 0.001) and had increased in-hospital mortality (28.4% vs 3.0%, P < 0.001). In multivariate analysis HFad was an independent predictor of death (OR: 4.88 [95%CI: 3.33-7.18], P < 0.001) and reperfusion adjusted to HFad was associated with lower mortality (OR: 0.57 [95%CI: 0.34-0.95], P = 0.03). HFad in STEMI is associated with a worse clinical profile, receives fewer reperfusion strategies, and carries a higher risk of in-hospital mortality while reperfusion reduces mortality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2024
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15. Stable isotopes reveal overlooked incorporation of diffuse land-based sources of nutrients and organic matter by intertidal communities at Rapa Nui (Easter Island).
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Zapata-Hernández G, Sellanes J, and Muñoz P
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- Carbon Isotopes analysis, Humans, Nitrogen Isotopes analysis, Nutrients, Ecosystem, Food Chain
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Rapa Nui is an important hotspot of endemic marine biodiversity, where diffuse land-based sources (e.g., nutrients and organic matter) entering into coastal waters could develop eutrophication in coastal environments, with deleterious impacts on the marine ecosystem. Stable isotopes (δ
13 C and δ15 N) of intertidal communities (macroalgae and invertebrates) were studied from sites with contrasting human influence (populated and unpopulated), to evaluate the incorporation and transfer of diffuse land-based sources through food webs. Macroalgae showed differences between some sites, and invertebrates showed a15 N-enrichment pattern at populated areas relative to unpopulated, being these differences significant in gastropods, barnacles and sea urchins. Moreover, trophic structure metrics suggest a higher trophic diversity in populated areas relative to unpopulated and support the isotopic partitioning between sites, associated with the incorporation of sources with15 N-enriched values. The above suggests that diffuse land-based sources could be incorporated by macroalgae, transferred into benthic consumers, and altering the trophic structure., (Copyright © 2022 Elsevier Ltd. All rights reserved.)- Published
- 2022
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16. Clinical Predictors of Hyperperfusion Syndrome Following Carotid Stenting: Results From a National Prospective Multicenter Study.
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González García A, Moniche F, Escudero-Martínez I, Mancha F, Tomasello A, Ribó M, Delgado-Acosta F, Ochoa JJ, de Las Heras JA, López-Mesonero L, González-Delgado M, Murias E, Gil J, Gil R, Zamarro J, Parrilla G, Mosteiro S, Fernández-Couto MD, Fernández de Alarcón L, Ramírez-Moreno JM, Luna A, Gil A, González-Mandly A, Caniego JL, Zapata-Wainberg G, García E, Alcázar PP, Ortega J, Arenillas JF, Algaba P, Zapata-Arriaza E, Alcalde-López J, de Albóniga-Chindurza A, Cayuela A, and Montaner J
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- Age Factors, Aged, Aged, 80 and over, Carotid Stenosis diagnostic imaging, Carotid Stenosis mortality, Carotid Stenosis physiopathology, Cerebrovascular Disorders diagnosis, Cerebrovascular Disorders mortality, Cerebrovascular Disorders physiopathology, Consciousness Disorders epidemiology, Consciousness Disorders physiopathology, Endovascular Procedures mortality, Female, Headache epidemiology, Headache physiopathology, Humans, Male, Middle Aged, Prospective Studies, Renal Insufficiency, Chronic epidemiology, Risk Assessment, Risk Factors, Seizures epidemiology, Seizures physiopathology, Severity of Illness Index, Sex Factors, Spain epidemiology, Time Factors, Treatment Outcome, Carotid Stenosis therapy, Cerebrovascular Circulation, Cerebrovascular Disorders epidemiology, Endovascular Procedures adverse effects, Endovascular Procedures instrumentation, Hemodynamics, Stents
- Abstract
Objectives: The aim of the HISPANIAS (HyperperfusIon Syndrome Post-carotid ANgIoplasty And Stenting) study was to define CHS rates and develop a clinical predictive model for cerebral hyperperfusion syndrome (CHS) after carotid artery stenting (CAS)., Background: CHS is a severe complication following CAS. The presence of clinical manifestations is estimated on the basis of retrospective reviews and is still uncertain., Methods: The HISPANIAS study was a national prospective multicenter study with 14 recruiting hospitals. CHS was classified as mild (headache only) and moderate-severe (seizure, impaired level of consciousness, or development of focal neurological signs)., Results: A total of 757 CAS procedures were performed. CHS occurred in 22 (2.9%) patients, in which 16 (2.1%) had moderate-severe CHS and 6 (0.8%) had mild CHS (only headache). The rate of hemorrhages was 0.7% and was associated with high mortality (20%). Pre-operative predictors of moderate-severe CHS in multivariate analysis were female sex (odds ratio [OR]: 3.24; 95% confidence interval [CI]: 1.11 to 9.47; p = 0.03), older patients (OR: 1.09; 95% CI: 1.01 to 1.17; p = 0.02), left carotid artery treated (OR: 4.13; 95% CI: 1.11 to 15.40; p = 0.03), and chronic renal failure (OR: 6.29; 95% CI: 1.75 to 22.57; p = 0.005). The area under the curve of this clinical and radiological model was 0.86 (95% CI: 0.81 to 0.92; p = 0.001)., Conclusions: The rate of CHS in the HISPANIAS study was 2.9%, with moderate-severe CHS of 2.1%. CHS was independently associated with female sex, older age, history of chronic kidney disease, and a treated left carotid artery. Although further investigations are needed, the authors propose a model to identify high-risk patients and develop strategies to decrease CHS morbidity and mortality in the future., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
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- 2019
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17. Syndromic congenital myelofibrosis associated with a loss-of-function variant in RBSN .
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Magoulas PL, Shchelochkov OA, Bainbridge MN, Ben-Shachar S, Yatsenko S, Potocki L, Lewis RA, Searby C, Marcogliese AN, Elghetany MT, Zapata G, Hernández PP, Gadkari M, Einhaus D, Muzny DM, Gibbs RA, Bertuch AA, Scott DA, Corvera S, and Franco LM
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- Abnormalities, Multiple genetics, Bone Marrow Transplantation, Child, Consanguinity, Fatal Outcome, Female, Gonadal Dysgenesis, 46,XY genetics, Hematopoietic Stem Cell Transplantation, Humans, Infant, Intellectual Disability genetics, Male, Pedigree, Phenotype, Primary Myelofibrosis congenital, Primary Myelofibrosis therapy, Syndrome, Vesicular Transport Proteins genetics, Vesicular Transport Proteins physiology, Primary Myelofibrosis genetics, Vesicular Transport Proteins deficiency
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- 2018
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18. Cardiomyocyte-specific deletion of the G protein-coupled estrogen receptor (GPER) leads to left ventricular dysfunction and adverse remodeling: A sex-specific gene profiling analysis.
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Wang H, Sun X, Chou J, Lin M, Ferrario CM, Zapata-Sudo G, and Groban L
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- Animals, Female, Male, Mice, Mice, Knockout, Myocytes, Cardiac pathology, Receptors, Estrogen metabolism, Receptors, G-Protein-Coupled metabolism, Sex Characteristics, Gene Deletion, Gene Expression Profiling, Gene Expression Regulation, Myocytes, Cardiac metabolism, Receptors, Estrogen genetics, Receptors, G-Protein-Coupled genetics, Ventricular Dysfunction, Left genetics, Ventricular Dysfunction, Left metabolism, Ventricular Dysfunction, Left pathology, Ventricular Remodeling genetics
- Abstract
Activation of G protein-coupled estrogen receptor (GPER) by its agonist, G1, protects the heart from stressors such as pressure-overload, ischemia, a high-salt diet, estrogen loss, and aging, in various male and female animal models. Due to nonspecific effects of G1, the exact functions of cardiac GPER cannot be concluded from studies using systemic G1 administration. Moreover, global knockdown of GPER affects glucose homeostasis, blood pressure, and many other cardiovascular-related systems, thereby confounding interpretation of its direct cardiac actions. We generated a cardiomyocyte-specific GPER knockout (KO) mouse model to specifically investigate the functions of GPER in cardiomyocytes. Compared to wild type mice, cardiomyocyte-specific GPER KO mice exhibited adverse alterations in cardiac structure and impaired systolic and diastolic function, as measured by echocardiography. Gene deletion effects on left ventricular dimensions were more profound in male KO mice compared to female KO mice. Analysis of DNA microarray data from isolated cardiomyocytes of wild type and KO mice revealed sex-based differences in gene expression profiles affecting multiple transcriptional networks. Gene Set Enrichment Analysis (GSEA) revealed that mitochondrial genes are enriched in GPER KO females, whereas inflammatory response genes are enriched in GPER KO males, compared to their wild type counterparts of the same sex. The cardiomyocyte-specific GPER KO mouse model provides us with a powerful tool to study the functions of GPER in cardiomyocytes. The gene expression profiles of the GPER KO mice provide foundational information for further study of the mechanisms underlying sex-specific cardioprotection by GPER., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2017
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19. Activation of GPR30 improves exercise capacity and skeletal muscle strength in senescent female Fischer344 × Brown Norway rats.
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Wang H, Alencar A, Lin M, Sun X, Sudo RT, Zapata-Sudo G, Lowe DA, and Groban L
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- Animals, Apoptosis, Cell Line, Estrogens metabolism, Exercise Test, Female, Gene Expression Regulation, Heat-Shock Proteins analysis, Heat-Shock Proteins genetics, Heat-Shock Proteins metabolism, Muscle Contraction, Ovariectomy, RNA, Messenger genetics, Rats, Inbred BN, Rats, Inbred F344, Receptors, G-Protein-Coupled agonists, Receptors, G-Protein-Coupled analysis, Receptors, G-Protein-Coupled genetics, Muscle Strength, Muscle, Skeletal physiology, Physical Conditioning, Animal, Receptors, G-Protein-Coupled metabolism
- Abstract
The molecular mechanisms of muscle weakness and sarcopenia in postmenopausal women are largely unknown. To determine the effect of a new estrogen receptor, GPR30, in the maintenance of exercise capacity and skeletal muscle function in females, the selective GPR30 agonist, G1 (100 μg/kg/day), or vehicle (V, soybean oil) was administered subcutaneously daily (n = 7 per group) to ovariectomized (OVX) 27-month-old Fischer 344 × Brown Norway (F344BN) female rats. Following 8 weeks of treatment, the exercise capacity (treadmill walk time to exhaustion) was reduced in OVX vs. sham rats (5.1 ± 1.4 vs. 11.0 ± 0.9 min, P < 0.05), and chronic G1 restored exercise capacity (12.9 ± 1.2 min; P < 0.05 vs. OVX-V). Similarly, the peak twitch of electrically stimulated soleus muscles was decreased by 22% in OVX vs. sham rats (P < 0.05), and G1 attenuated this decline (P < 0.05). Western blot analysis showed that chronic G1 treatment attenuated OVX-associated decreases in heat shock protein (HSP) 90, HSP70, and HSP27 expressions. In vitro studies using the L6 myoblast cell line demonstrated that G1 increased mRNA levels of HSPs in cultured cells. Collectively, these data demonstrate that the activation of GPR30 mitigates the adverse effects of estrogen loss on exercise capacity and skeletal muscle contractile function in old F344BN rats. The protective effects of GPR30 might be through its upregulation of heat shock proteins in skeletal muscle., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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20. Screening exons 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer's disease.
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Barber IS, García-Cárdenas JM, Sakdapanichkul C, Deacon C, Zapata Erazo G, Guerreiro R, Bras J, Hernandez D, Singleton A, Guetta-Baranes T, Braae A, Clement N, Patel T, Brookes K, Medway C, Chappell S, Mann DM, and Morgan K
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- Aged, Base Pairing genetics, Cohort Studies, Female, Gene Deletion, Gene Frequency, Genetic Testing, Humans, Introns genetics, Male, Middle Aged, Sequence Analysis, DNA, Alzheimer Disease genetics, Amyloid beta-Protein Precursor genetics, Exons genetics, Genetic Association Studies, Mutation
- Abstract
Early-onset Alzheimer's disease (EOAD) can be familial (FAD) or sporadic EOAD (sEOAD); both have a disease onset ≤65 years of age. A total of 451 sEOAD samples were screened for known causative mutations in exons 16 and 17 of the amyloid precursor protein (APP) gene. Four samples were shown to be heterozygous for 1 of 3 known causative mutations: p.A713T, p.V717I, and p.V717G; this highlights the importance of screening EOAD patients for causative mutations. Additionally, we document an intronic 6 base pair (bp) deletion located 83 bp downstream of exon 17 (rs367709245, IVS17 83-88delAAGTAT), which has a nonsignificantly increased minor allele frequency in our sEOAD cohort (0.006) compared to LOAD (0.002) and controls (0.002). To assess the effect of the 6-bp deletion on splicing, COS-7 and BE(2)-C cells were transfected with a minigene vector encompassing exon 17. There was no change in splicing of exon 17 from constructs containing either wild type or deletion inserts. Sequencing of cDNA generated from cerebellum and temporal cortex of a patient harboring the deletion found no evidence of transcripts with exon 17 removed., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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21. Local and systemic toxicity of intravitreal melphalan for vitreous seeding in retinoblastoma: a preclinical and clinical study.
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Francis JH, Schaiquevich P, Buitrago E, Del Sole MJ, Zapata G, Croxatto JO, Marr BP, Brodie SE, Berra A, Chantada GL, and Abramson DH
- Subjects
- Animals, Antineoplastic Agents, Alkylating administration & dosage, Antineoplastic Agents, Alkylating adverse effects, Blood Cell Count, Child, Child, Preschool, Drug Evaluation, Preclinical, Electroretinography, Female, Fluorescein Angiography, Humans, Infant, Intravitreal Injections, Male, Melphalan administration & dosage, Melphalan adverse effects, Prospective Studies, Rabbits, Regression Analysis, Retinal Neoplasms physiopathology, Retinoblastoma physiopathology, Vitreous Body pathology, Antineoplastic Agents, Alkylating toxicity, Melphalan toxicity, Neoplasm Seeding, Retinal Neoplasms drug therapy, Retinoblastoma drug therapy
- Abstract
Purpose: Intravitreal melphalan is emerging as an effective treatment for refractory vitreous seeds in retinoblastoma, but there is limited understanding regarding its toxicity. This study evaluates the retinal and systemic toxicity of intravitreal melphalan in retinoblastoma patients, with preclinical validation in a rabbit model., Design: Clinical and preclinical, prospective, cohort study., Participants: In the clinical study, 16 patient eyes received 107 intravitreal injections of 30 μg melphalan given weekly, a median of 6.5 times (range, 5-8). In the animal study, 12 New Zealand/Dutch Belt pigmented rabbits were given 3 weekly injections of 15 μg of intravitreal melphalan or vehicle to the right eye., Methods: Electroretinogram (ERG) responses were recorded in both humans and rabbits. For the clinical study, ERG responses were recorded at baseline, immediately before each injection, and at each follow-up visit; 82 of these studies were deemed evaluable. Median follow-up time was 5.2 months (range, 1-11). Complete blood counts (CBCs) were obtained on the day of injection at 46 patient visits. In the animal study, ERG responses were obtained along with fluorescein angiography, CBCs, and melphalan plasma concentration. After humane killing, the histopathology of the eyes was evaluated., Main Outcome Measures: For the clinical study, we measured peak-to-peak ERG amplitudes in response to 30-Hz photopic flicker stimulation with comparisons between ERG studies before and after intravitreal melphalan. For the animal study, we collected ERG parameters before and after intravitreal melphalan injections with histopathologic findings., Results: By linear regression analysis, over the course of weekly intravitreal injections in retinoblastoma patients, for every additional injection, the ERG amplitude decreased by approximately 5.8 μV. The ERG remained stable once the treatment course was completed. In retinoblastoma patients, there were no grade 3 or 4 hematologic events. One week after the second injection in rabbits, the a- and b-wave amplitude declined significantly in the melphalan treated eyes compared with vehicle-treated eyes (P<0.05). Histopathology revealed severely atrophic retina., Conclusions: Weekly injections of 30 μg of melphalan can result in a decreased ERG response, which is indicative of retinal toxicity. These findings are confirmed at an equivalent dose in rabbit eyes by ERG measurements and by histopathologic evidence of severe retinal damage. Systemic toxicity with intravitreal melphalan at these doses in humans or rabbits was not detected., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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22. N-acylhydrazone derivative ameliorates monocrotaline-induced pulmonary hypertension through the modulation of adenosine AA2R activity.
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Alencar AK, Pereira SL, da Silva FE, Mendes LV, Cunha Vdo M, Lima LM, Montagnoli TL, Caruso-Neves C, Ferraz EB, Tesch R, Nascimento JH, Sant'anna CM, Fraga CA, Barreiro EJ, Sudo RT, and Zapata-Sudo G
- Subjects
- Adenosine A2 Receptor Agonists chemistry, Animals, Benzamides chemistry, Exercise Tolerance drug effects, Hydrazones chemistry, Hypertension, Pulmonary chemically induced, Hypertension, Pulmonary diagnostic imaging, Hypertrophy, Right Ventricular chemically induced, Hypertrophy, Right Ventricular diagnostic imaging, Hypertrophy, Right Ventricular drug therapy, Male, Nitric Oxide Synthase Type III metabolism, Pulmonary Artery diagnostic imaging, Pulmonary Artery drug effects, Pulmonary Artery metabolism, Rats, Wistar, Ultrasonography, Vasodilation drug effects, Adenosine A2 Receptor Agonists pharmacology, Benzamides pharmacology, Hydrazones pharmacology, Hypertension, Pulmonary drug therapy, Monocrotaline pharmacology, Receptor, Adenosine A2A metabolism
- Abstract
Background: Pulmonary arterial hypertension (PAH) is a disease that results in right ventricular (RV) dysfunction. While pulmonary vascular disease is the primary pathological focus, RV hypertrophy and RV dysfunction are the major determinants of prognosis in PAH. The aim of this study was to investigate the effects of (E)-N'-(3,4-dimethoxybenzylidene)-4-methoxybenzohydrazide (LASSBio-1386), an N-acylhydrazone derivative, on the lung vasculature and RV dysfunction induced by experimental PAH., Methods: Male Wistar rats were injected with a single dose (60mg/kg, i.p.) of monocrotaline (MCT) and given LASSBio-1386 (50mg/kg, p.o.) or vehicle for 14 days. The hemodynamic, exercise capacity (EC), endothelial nitric oxide synthase (eNOS), adenosine A2A receptor (A2AR), sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA2a), phospholamban (PLB) expression, Ca(2+)-ATPase activity and vascular activity of LASSBio-1386 were evaluated., Results and Conclusions: The RV systolic pressure was elevated in the PAH model and reduced from 49.6 ± 5.0 mm Hg (MCT group) to 27.2 ± 2.1 mm Hg (MCT+LASSBio-1386 group; P<0.05). MCT administration also impaired the EC, increased the RV and pulmonary arteriole size, and promoted endothelial dysfunction of the pulmonary artery rings. In the PAH group, the eNOS, A2AR, SERCA2a, and PLB levels were changed compared with the control; in addition, the Ca(2+)-ATPase activity was reduced. These alterations were related with MCT-injected rats, and LASSBio-1386 had favorable effects that prevented the development of PAH. LASSBio-1386 is effective at preventing endothelial and RV dysfunction in PAH, a finding that may have important implications for ongoing clinical evaluation of A2AR agonists for the treatment of PAH., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2014
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23. N-acylhydrazone improves exercise intolerance in rats submitted to myocardial infarction by the recovery of calcium homeostasis in skeletal muscle.
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da Silva JS, Pereira SL, Maia Rdo C, Landgraf SS, Caruso-Neves C, Kümmerle AE, Fraga CA, Barreiro EJ, Sudo RT, and Zapata-Sudo G
- Subjects
- Animals, Caffeine pharmacology, Disease Models, Animal, Exercise Tolerance physiology, Homeostasis, Male, Muscle Contraction drug effects, Muscle Contraction physiology, Muscle Fatigue physiology, Muscle, Skeletal metabolism, Muscle, Skeletal physiology, Physical Conditioning, Animal physiology, Rats, Rats, Wistar, Sarcoplasmic Reticulum Calcium-Transporting ATPases metabolism, Time Factors, Calcium metabolism, Exercise Tolerance drug effects, Hydrazones pharmacology, Muscle Fatigue drug effects, Myocardial Infarction physiopathology, Thiophenes pharmacology
- Abstract
Aims: This work investigated the effects of 3,4-methylenedioxybenzoyl-2-thienylhydrazone (LASSBio-294) treatment on the contractile response of soleus (SOL) muscle from rats submitted to myocardial infarction (MI)., Main Methods: Following coronary artery ligation, LASSBio-294 (2mg/kg, i.p.) or vehicle was administrated once daily for 4 weeks., Key Findings: The run time to fatigue for sham rats was 17.9 ±2.6 min, and it was reduced to 3.3 ± 0.8 min (P<0.05) in MI rats. In MI rats treated with LASSBio-294, the time to fatigue was 15.1 ± 3.6 min. During the contractile test, SOL muscles from sham rats showed a response of 7.12 ± 0.54N/cm(2) at 60 Hz, which was decreased to 5.45 ± 0.49 N/cm(2) (P<0.05) in MI rats. The contractility of SOL muscles from the MI-LASSBio-294 group was increased to 9.01 ± 0.65N/cm(2). At 16 mM caffeine, the contractility was reduced from 2.31 ± 0.33 to 1.60 ± 0.21 N/cm(2) (P<0.05) in the MI group. In SOL muscles from MI-LASSBio-294 rats, the caffeine response was increased to 2.62 ± 0.33 N/cm(2). Moreover, SERCA2a expression in SOL muscles was decreased by 0.31-fold (31%) in the MI group compared to the Sham group (P<0.05). In the MI-LASSBio-294 group, it was increased by 1.53-fold (153%) compared to the MI group (P<0.05). Meanwhile, the nuclear density in SOL muscles was increased in the MI group compared to the Sham group. Treatment with LASSBio-294 prevented this enhancement of cellular infiltrate., Significance: LASSBio-294 treatment prevented the development of muscular fatigue and improved exercise intolerance in rats submitted to MI., (Copyright © 2014 Elsevier Inc. All rights reserved.)
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- 2014
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24. Could a high-fat diet rich in unsaturated fatty acids impair the cardiovascular system?
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Medei E, Lima-Leopoldo AP, Pereira-Junior PP, Leopoldo AS, Campos DH, Raimundo JM, Sudo RT, Zapata-Sudo G, Bruder-Nascimento T, Cordellini S, Nascimento JH, and Cicogna AC
- Subjects
- Animals, Male, Rats, Rats, Wistar, Cardiovascular Diseases prevention & control, Dietary Fats administration & dosage, Fatty Acids, Unsaturated administration & dosage
- Abstract
Background: Dyslipidemia results from consumption of a diet rich in saturated fatty acids and is usually associated with cardiovascular disease. A diet rich in unsaturated fatty acids is usually associated with improved cardiovascular condition., Objective: To investigate whether a high-fat diet rich in unsaturated fatty acids (U-HFD) - in which fatty acid represents approximately 45% of the total calories - impairs the cardiovascular system., Methods: Male, 30-day-old Wistar rats were fed a standard (control) diet or a U-HFD containing 83% unsaturated fatty acid for 19 weeks. The in vivo electrocardiogram, the spectral analysis of heart rate variability, and the vascular reactivity responses to phenylephrine, acetylcholine, noradrenaline and prazosin in aortic ring preparations were analyzed to assess the cardiovascular parameters., Results: After 19 weeks, the U-HFD rats had increased total body fat, baseline glucose levels and feed efficiency compared with control rats. However, the final body weight, systolic blood pressure, area under the curve for glucose, calorie intake and heart weight⁄final body weight ratio were similar between the groups. In addition, both groups demonstrated no alteration in the electrocardiogram or cardiac sympathetic parameters. There was no difference in the responses to acetylcholine or the maximal contractile response of the thoracic aorta to phenylephrine between groups, but the concentration necessary to produce 50% of maximal response showed a decrease in the sensitivity to phenylephrine in U-HFD rats. The cumulative concentration- effect curve for noradrenaline in the presence of prazosin was shifted similarly in both groups., Conclusions: The present work shows that U-HFD did not impair the cardiovascular parameters analyzed.
- Published
- 2010
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25. Sedation and antinociception induced by a new pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine derivative (LASSBio-873) is modulated by activation of muscarinic receptors.
- Author
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Mendes TC, Raimundo JM, Nascimento-Junior NM, Fraga CA, Barreiro EJ, Sudo RT, and Zapata-Sudo G
- Subjects
- Adrenergic alpha-Antagonists metabolism, Analgesics administration & dosage, Analysis of Variance, Animals, Behavior, Animal drug effects, Dose-Response Relationship, Drug, Exploratory Behavior drug effects, GABA Antagonists metabolism, Hot Temperature, Hyperalgesia drug therapy, Hypnotics and Sedatives administration & dosage, Inflammation chemically induced, Inflammation physiopathology, Male, Mice, Motor Activity drug effects, Muscarinic Antagonists metabolism, Narcotic Antagonists metabolism, Pain Measurement, Pyrazoles administration & dosage, Pyridines administration & dosage, Pyrroles administration & dosage, Analgesics pharmacology, Hypnotics and Sedatives pharmacology, Pain drug therapy, Pyrazoles pharmacology, Pyridines pharmacology, Pyrroles pharmacology, Receptors, Muscarinic metabolism
- Abstract
New substances designed for the treatment of anxiety have previously been synthesized, which resulted in the identification of four new pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine derivatives structurally designed by using zolpidem as lead compound. Among them, LASSBio-873 was the most potent to produce analgesic, sedative and hypnotic effects. Thus, we investigated the possible mechanisms involved in LASSBio-873-induced sedation, as well as its effects on different models of inflammatory pain. LASSBio-873 (4 mg/kg) reduced locomotor activity of mice in the open field test from 205.2+/-25.6 to 87.6+/-16.2 movements/min. Atropine, a non-selective muscarinic antagonist, prevented the LASSBio-873-induced sedation and increased locomotor activity to 192.9+/-30.2 movements/min. In the formalin test, LASSBio-873 (4 mg/kg) significantly reduced the duration of nociceptive behavior during the inflammatory phase, reducing the control reactivity from 197.6+/-14.5s to 84.4+/-10.3s. Carrageenan reduced the latency for the animal reaction from 5.1+/-0.2s (control) to 2.1+/-0.3s which was completely reverted by LASSBio-873 (6 mg/kg) to 5.6+/-0.6s. Atropine prevented the LASSBio-873-induced antinociceptive and antihyperalgesic activities, indicating the interference of the cholinergic system. LASSBio-873 is a novel prototype of drug that modulates muscarinic activity and could be used for neuropsychiatric and cognitive disorders and other conditions associated to acute and chronic pain.
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- 2009
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26. Sedative-hypnotic profile of novel isatin ketals.
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Zapata-Sudo G, Pontes LB, Gabriel D, Mendes TC, Ribeiro NM, Pinto AC, Trachez MM, and Sudo RT
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- Animals, Drug Evaluation, Preclinical, Hypnotics and Sedatives chemistry, Isatin chemistry, Isatin pharmacology, Male, Mice, Molecular Structure, Motor Activity drug effects, Pentobarbital pharmacology, Rats, Rats, Wistar, Sleep drug effects, Structure-Activity Relationship, Hypnotics and Sedatives pharmacology, Isatin analogs & derivatives
- Abstract
Isatin (1H-indol-2,3-dione) is an endogenous compound found in many tissues and fluids. Isatin and its derivatives exert pharmacological effects on the central nervous system, including anxiogenic, sedative and anticonvulsant activities. Two new groups of isatin derivatives were synthesized (nine dioxolane ketals and nine dioxane ketals) and studied for their sedative, hypnotic and anesthetic effects using pentobarbital-induced sleeping time, locomotor activity evaluation and intravenous infusion. The dioxolane ketals were more potent than dioxane ketals for inducing sedative-hypnotic states, causing up to a three-fold increase in pentobarbital hypnosis. The dioxolane ketals produced sedation, demonstrated by decreased spontaneous locomotor activity in an open field. Hypnosis and anesthesia were observed during intravenous infusion of 5'-chlorospiro-[1,3-dioxolane-2,3'-indolin]-2'-one (T3) in conscious Wistar rats. Complete recovery from hypnosis and anesthesia required 39.1+/-7.3 and 6.8+/-2.4 min, respectively. Changes in hemodynamic parameters after infusion of 5.0 mg/kg/min were minimal. These findings suggest that these new isatin derivatives represent potential candidates for the development of new drugs that act on the central nervous system and may lead to a new centrally acting anesthetic with no toxic effects on the cardiovascular or respiratory systems.
- Published
- 2007
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27. A theory of protein-resin interaction in hydrophobic interaction chromatography.
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Mahn A, Zapata-Torres G, and Asenjo JA
- Subjects
- Binding Sites, Hydrophobic and Hydrophilic Interactions, Models, Chemical, Models, Molecular, Protein Conformation, Ribonucleases chemistry, Thermodynamics, Chromatography methods, Proteins chemistry, Sepharose analogs & derivatives, Sepharose chemistry
- Abstract
Docking simulations were performed in order to investigate surface area of interaction between several ribonucleases and a reduced model for the hydrophobic moiety used in Phenyl Sepharose using the program AutoDock 3.0. For each ribonucelase, 80 independent simulations with populations consisting of 100 random structures were performed and from these the most probable docked protein-ligand conformations were obtained. A new methodology was used to select the most probable conformations, based on qualitative and quantitative considerations. The interacting amino acids in each protein were identified. The average surface hydrophobicity of the interfacial zone (local hydrophobicity, LH) was determined. The LH showed a high correlation level (r2 = 0.99) with the "hydrophobic contact area" (HCA) experimentally determined for the different ribonucleases as well as with the dimensionless retention time (r2 = 0.90). This study allowed us to identify the zones on the protein surface most probably involved in protein retention in HIC, without tedious experimental work. Given the good correlation level obtained, this new methodology may constitute a novel approach that could be used to predict protein behavior in HIC.
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- 2005
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28. Analgesic and behavioral effects of amphetamine enantiomers, p-methoxyamphetamine and n-alkyl-p-methoxyamphetamine derivatives.
- Author
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Bustamante D, Díaz-Véliz G, Paeile C, Zapata-Torres G, and Cassels BK
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- Amphetamine chemistry, Amphetamine pharmacology, Amphetamines chemistry, Analgesics chemistry, Animals, Avoidance Learning drug effects, Dextroamphetamine chemistry, Dextroamphetamine pharmacology, Female, Grooming drug effects, Male, Motor Activity drug effects, Pain Measurement, Rats, Rats, Sprague-Dawley, Stereoisomerism, Structure-Activity Relationship, Amphetamines pharmacology, Analgesics pharmacology, Behavior, Animal drug effects
- Abstract
The analgesic effects of (+)- and (-)-amphetamine (AMPH), (+/-)-p-methoxyamphetamine (MA), (+/-)-N-methyl-p-methoxyamphetamine (MMA) and (+/-)-N-ethyl-p-methoxyamphetamine (EMA) were compared using two different algesimetric tests in rats. In the formalin test, (+)-AMPH elicited significant antinociception at doses of 0.2, 2 and 8 mg/kg (i.p.); (-)-AMPH was active at 2 and 8 mg/kg, but not at 0.2 mg/kg; MA elicited very potent and long-lasting antinociception; MMA was less active than MA; EMA showed significant effects only at doses of 2 and 8 mg/kg. In the C-fiber evoked nociceptive reflex assay, i.v. (+)- and (-)-AMPH were ineffective, but the methoxy derivatives showed a similar pattern of action combining inhibitory and excitatory actions. To clarify apparent discrepancies between both algesimetric tests, some behavioral motor performance tests were carried out. These tests confirm the motor stimulatory properties of (+)-AMPH, not shared by the methoxylated amphetamine derivatives. The three methoxy derivatives elicited some stereotypies related to dopaminergic activation such as grooming behavior. (+)-AMPH was also the only drug to increase the acquisition of CARs while MA and EMA were without effect. Avoidance conditioning was seriously impaired in rats injected with MMA. This conditioned behavior can be related to the significant decrease of spontaneous motor activity observed with this drug. In conclusion, the introduction of a para-methoxy group strongly increases the analgesic effects of amphetamine without its stimulatory behavioral effects. The introduction of N-alkyl substituents decreases the analgesic potency of MA.
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- 2004
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29. Vitamin E and linoleic acid in the feeding of premature infants.
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Panos TC, Stinnett B, Zapata G, Eminians J, Marasigan BV, and Beard AG
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- Anemia, Animals, Body Weight, Chromium Isotopes, Diet, Erythrocytes metabolism, Female, Hemoglobins, Hemolysis, Humans, Infant, Newborn, Male, Milk, Reticulocytes, Vitamin E blood, Vitamin E Deficiency, Dietary Fats pharmacology, Infant Nutritional Physiological Phenomena drug effects, Infant, Premature, Linoleic Acids pharmacology, Vitamin E pharmacology
- Published
- 1968
- Full Text
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