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2. Nanostructure engineering of epitaxial piezoelectric {\alpha}-quartz thin films on silicon

Author

Zhang, Q., Sánchez-garcia, D., Desgarceaux, R., Gomez, A., Escofet-Majora, P., Oró-soler, J., Gazquez, J., Larrieu, G., Charlot, B., Gich, M., and Carretero-Genevrier, A.

Subjects
Physics - Applied Physics, Condensed Matter - Materials Science
Abstract

The monolithic integration of sub-micron quartz structures on silicon substrates is a key issue for the future development of telecommunication to the GHz frequencies. Here we report unprecedented large-scale fabrication of ordered arrays of piezoelectric epitaxial quartz nanostructures on silicon substrates by the combination of soft-chemistry and three cost effective lithographic techniques: (i) laser transfer lithography, (ii) soft nanoimprint lithography on Sr-doped SiO2 sol-gel thin films and (iii) self-assembled SrCO3 nanoparticles reactive nanomasks. Epitaxial {\alpha}-quartz nanopillars with different diameters (down to 50 nm) and heights (up to 2000 nm) were obtained for the first time. This work proves the control over the shape, micro- and nano-patterning of quartz thin films while preserving its crystallinity, texture and piezoelectricity. This work opens up the opportunity to fabricate new high frequency resonators and high sensitivity sensors relevant in different fields of application.

Published
2019

5. Automatic calculation of pelvis morphology from CT images

Author

Guijarro Martínez, P., Sánchez García, D., Cubero, L., León-Luis, J. De, Pascau, J., Guijarro Martínez, P., Sánchez García, D., Cubero, L., León-Luis, J. De, and Pascau, J.

Abstract

Pelvimetry is the study of the pelvis morphology in women for labor planning and medical assessment. This can be achieved by manually annotating pelvic CT images for extracting several measures of interest, which can be both time-consuming and subjective. While machine learning has achieved significant success in 2D landmarking applications, results in pelvic CT images are still limited, particularly with small datasets. This paper presents a two-step approach for detecting 3D landmarks in pelvic CT images. First, a simple CNN coarsely estimates landmark locations, serving as a starting point for further refinement. Then, higher resolution 3D patches and independent neural networks are used to obtain the final position for each landmark. Our model has shown promising results, obtaining an average distance error of 6.71 mm across 7 landmarks. These values allowed the calculation of the morphological measurements, demonstrating a strong correlation with the manual values. The proposed model has shown promising results, offering efficient and accurate predictions of the anatomical landmarks in CT examinations.

Published
2023

6. Desarrollo de un nuevo SMC sostenible con una resina termoplástica

Author

Ministerio de Ciencia e Innovación (España), Martín Crespo, D., Santiago Bethencour, A., Sánchez García, D., Ares-Elejoste, P., Gondra, K., Verdejo, Raquel, López-Manchado, Miguel A., Ministerio de Ciencia e Innovación (España), Martín Crespo, D., Santiago Bethencour, A., Sánchez García, D., Ares-Elejoste, P., Gondra, K., Verdejo, Raquel, and López-Manchado, Miguel A.

Abstract

El SMC (sheet molding compound) es un material compuesto comúnmente usado para fabricar piezas por un proceso de moldeo por compresión en caliente. Este compuesto cuenta con dos características claves para el sector de la automoción: permite producir piezas con una elevada cadencia y presenta una gran flexibilidad para el diseño de piezas de diversas formas y tamaños. Su gran inconveniente, como el de los materiales compuestos, en general, es que no se pueden reciclar y al final de su vida útil terminan almacenados en vertederos. En este trabajo, presentamos un nuevo SMC sostenible fácilmente reciclable mediante el uso de una resina termoplástica líquida patentada en el CSIC, SMC (sheet moulding compound) is a composite material commonly used to manufacture parts by a hot compression moulding process. This composite has two key characteristics for the automotive sector: it allows parts to be produced at a high rate of production and it has great flexibility for the design of parts of various shapes and sizes. However, like other composite materials, its primary drawback lies in the limited recyclability, resulting in their disposal in landfills at the end of their lifespan. In this work, we present a new and sustainable SMC using a liquid thermoplastic resin patented at CSIC

Published
2023

7. Elective cancer surgery in COVID-19–Free surgical pathways during the SARS-cov-2 pandemic: An international, multicenter, comparative cohort study

Author

James C Glasbey, Dmitri Nepogodiev, Joana Ff Simoes, Omar Omar, Elizabeth Li, Mary L Venn, Mohammad Abou Chaar, Vita Capizzi, Daoud Chaudhry, Anant Desai, Jonathan G Edwards, Jonathan P Evans, Marco Fiore, Jose Flavio Videria, Samuel J Ford, Ian Ganyli, Ewen A Griffiths, Rohan R Gujjuri, Angelos G Kolias, Haytham Ma Kaafarani, Ana Minaya-Bravo, Siobhan C McKay, Helen M Mohan, Keith Roberts, Carlos San Miguel-Méndez, Peter Pockney, Richard Shaw, Neil J Smart, Grant D Stewart, Sudha Sundar, Raghavan Vidya, Aneel A Bhangu, James C Glasbey, Omar Omar, Aneel A Bhangu, Kwabena Siaw-Acheampong, Ruth A Benson, Edward Bywater, Daoud Chaudhry, Brett E Dawson, Jonathan P Evans, James C Glasbey, Rohan R Gujjuri, Emily Heritage, Conor S Jones, Sivesh K Kamarajah, Chetan Khatri, Rachel A Khaw, James M Keatley, Andrew Knight, Samuel Lawday, Elizabeth Li, Harvinder S Mann, Ella J Marson, Kenneth A McLean, Siobhan C McKay, Emily C Mills, Dmitri Nepogodiev, Gianluca Pellino, Maria Picciochi, Elliott H Taylor, Abhinav Tiwari, Joana Ff Simoes, Isobel M Trout, Mary L Venn, Richard Jw Wilkin, Aneel A Bhangu, James C Glasbey, Neil J Smart, Ana Minaya-Bravo, Jonathan P Evans, Gaetano Gallo, Susan Moug, Francesco Pata, Peter Pockney, Salomone Di Saverio, Abigail Vallance, Dale Vimalchandran, Ewen A Griffiths, Sivesh K Kamarajah, Richard Pt Evans, Philip Townend, Keith Roberts, Siobhan McKay, John Isaac, Sohei Satoi, John Edwards, Aman S Coonar, Adrian Marchbank, Edward J Caruana, Georgia R Layton, Akshay Patel, Alessandro Brunelli, Samuel Ford, Anant Desai, Alessandro Gronchi, Marco Fiore, Max Almond, Fabio Tirotta, Sinziana Dumitra, Angelos Kolias, Stephen J Price, Daniel M Fountain, Michael D Jenkinson, Peter Hutchinson, Hani J Marcus, Rory J Piper, Laura Lippa, Franco Servadei, Ignatius Esene, Christian Freyschlag, Iuri Neville, Gail Rosseau, Karl Schaller, Andreas K Demetriades, Faith Robertson, Alex Alamri, Richard Shaw, Andrew G Schache, Stuart C Winter, Michael Ho, Paul Nankivell, Juan Rey Biel, Martin Batstone, Ian Ganly, Raghavan Vidya, Alex Wilkins, Jagdeep K Singh, Dinesh Thekinkattil, Sudha Sundar, Christina Fotopoulou, Elaine Leung, Tabassum Khan, Luis Chiva, Jalid Sehouli, Anna Fagotti, Paul Cohen, Murat Gutelkin, Rahel Ghebre, Thomas Konney, Rene Pareja, Rob Bristow, Sean Dowdy, T S Shylasree, R Kottayasamy Seenivasagam, Joe Ng, Keiiji Fujiwara, Grant D Stewart, Benjamin Lamb, Krishna Narahari, Alan McNeill, Alexandra Colquhoun, John McGrath, Steve Bromage, Ravi Barod, Veeru Kasivisvanathan, Tobias Klatte, Joana Ff Simoes, Tom Ef Abbott, Sadi Abukhalaf, Michel Adamina, Adesoji O Ademuyiwa, Arnav Agarwal, Murat Akkulak, Ehab Alameer, Derek Alderson, Felix Alakaloko, Markus Albertsmeiers, Osaid Alser, Muhammad Alshaar, Sattar Alshryda, Alexis P Arnaud, Knut Magne Augestad, Faris Ayasra, José Azevedo, Brittany K Bankhead-Kendall, Emma Barlow, David Beard, Ruth A Benson, Ruth Blanco-Colino, Amanpreet Brar, Ana Minaya-Bravo, Kerry A Breen, Chris Bretherton, Igor Lima Buarque, Joshua Burke, Edward J Caruana, Mohammad Chaar, Sohini Chakrabortee, Peter Christensen, Daniel Cox, Moises Cukier, Miguel F Cunha, Giana H Davidson, Anant Desai, Salomone Di Saverio, Thomas M Drake, John G Edwards, Muhammed Elhadi, Sameh Emile, Shebani Farik, Marco Fiore, J Edward Fitzgerald, Samuel Ford, Tatiana Garmanova, Gaetano Gallo, Dhruv Ghosh, Gustavo Mendonça Ataíde Gomes, Gustavo Grecinos, Ewen A Griffiths, Madalegna GrÜndl, Constantine Halkias, Ewen M Harrison, Intisar Hisham, Peter J Hutchinson, Shelley Hwang, Arda Isik, Michael D Jenkinson, Pascal Jonker, Haytham Ma Kaafarani, Debby Keller, Angelos Kolias, Schelto Kruijff, Ismail Lawani, Hans Lederhuber, Sezai Leventoglu, Andrey Litvin, Andrew Loehrer, Markus W Löffler, Maria Aguilera Lorena, Maria Marta Modolo, Piotr Major, Janet Martin, Hassan N Mashbari, Dennis Mazingi, Symeon Metallidis, Ana Minaya-Bravo, Helen M Mohan, Rachel Moore, David Moszkowicz, Susan Moug, Joshua S Ng-Kamstra, Mayaba Maimbo, Ionut Negoi, Milagros Niquen, Faustin Ntirenganya, Maricarmen Olivos, Kacimi Oussama, Oumaima Outani, Marie Dione Parreno-Sacdalanm, Francesco Pata, Carlos Jose Perez Rivera, Thomas D Pinkney, Willemijn van der Plas, Peter Pockney, Ahmad Qureshi, Dejan Radenkovic, Antonio Ramos-De la Medina, Keith Roberts, April C Roslani, Martin Rutegård, Juan José Segura-Sampedro, Irène Santos, Sohei Satoi, Raza Sayyed, Andrew Schache, Andreas A Schnitzbauer, Justina O Seyi-Olajide, Neil Sharma, Richard Shaw, Sebastian Shu, Kjetil Soreide, Antonino Spinelli, Grant D Stewart, Malin Sund, Sudha Sundar, Stephen Tabiri, Philip Townend, Georgios Tsoulfas, Gabrielle H van Ramshorst, Raghavan Vidya, Dale Vimalachandran, Oliver J Warren, Duane Wedderburn, Naomi Wright, C Allemand, L Boccalatte, M Figari, M Lamm, J Larrañaga, C Marchitelli, F Noll, D Odetto, M Perrotta, J Saadi, L Zamora, C Alurralde, E L Caram, D Eskinazi, J P Mendoza, M Usandivaras, R Badra, A Esteban, J S García, P M García, J I Gerchunoff, S M Lucchini, M A NIgra, L Vargas, T Hovhannisyan, A Stepanyan, T Gould, R Gourlay, B Griffiths, S Gananadha, M McLaren, J Cecire, N Joshi, S Salindera, A Sutherland, J H Ahn, G Charlton, S Chen, N Gauri, R Hayhurst, S Jang, F Jia, C Mulligan, W Yang, G Ye, H Zhang, M Ballal, D Gibson, D Hayne, J Moss, T Richards, P Viswambaram, U G Vo, J Bennetts, T Bright, M Brooke-Smith, R Fong, B Gricks, Y H Lam, B S Ong, M Szpytma, D Watson, K Bagraith, S Caird, E Chan, C Dawson, D Ho, E Jeyarajan, S Jordan, A Lim, G J Nolan, A Oar, D Parker, H Puhalla, A Quennell, L Rutherford, P Townend, M Von Papen, M Wullschleger, A Blatt, D Cope, N Egoroff, M Fenton, J Gani, N Lott, P Pockney, N Shugg, M Elliott, D Phung, D Phan, D Townend, C Bong, J Gundara, A Frankel, S Bowman, G R Guerra, J Bolt, K Buddingh, N N Dudi-Venkata, S Jog, H M Kroon, T Sammour, R Smith, C Stranz, M Batstone, K Lah, W McGahan, D Mitchell, A Morton, A Pearce, M Roberts, G Sheahan, B Swinson, N Alam, S Banting, L Chong, P Choong, S Clatworthy, D Foley, A Fox, M W Hii, B Knowles, J Mack, M Read, A Rowcroft, S Ward, G Wright, M Lanner, I Königsrainer, M Bauer, C Freyschlag, M Kafka, F Messner, D Öfner, I Tsibulak, K Emmanuel, M Grechenig, R Gruber, M Harald, L Öhlberger, J Presl, A Wimmer, I Namazov, E Samadov, D Barker, R Boyce, S Corbin, A Doyle, A Eastmond, R Gill, A Haynes, S Millar, M O'Shea, G Padmore, N Paquette, E Phillips, S St John, K Walkes, N Flamey, P Pattyn, W Oosterlinck, J Van den Eynde, R Van den Eynde, A Gatti, C Nardi, R Oliva, R De Cicco, I Cecconello, P Gregorio, L Pontual Lima, U Ribeiro Junior, F Takeda, R M Terra, M Sokolov, B Kidane, S Srinathan, M Boutros, N Caminsky, G Ghitulescu, G Jamjoum, J Moon, J Pelletier, T Vanounou, S Wong, M Boutros, S Dumitra, A Kouyoumdjian, B Johnston, C Russell, M Boutros, S Demyttenaere, R Garfinkle, J Abou-Khalil, C Nessim, J Stevenson, F Heredia, A Almeciga, A Fletcher, A Merchan, L O Puentes, J Mendoza Quevedo, G Bacic, D Karlovic, D Krsul, M Zelic, I Luksic, M Mamic, B Bakmaz, I Coza, E Dijan, Z Katusic, J Mihanovic, I Rakvin, K Frantzeskou, N Gouvas, G Kokkinos, P Papatheodorou, I Pozotou, O Stavrinidou, A Yiallourou, L Martinek, M Skrovina, I Szubota, J Žatecký, V Javurkova, J Klat, T Avlund, P Christensen, J L Harbjerg, L H Iversen, D W Kjaer, Hø Kristensen, M Mekhael, A L Ebbehøj, P Krarup, N Schlesinger, H Smith, A Abdelsamed, A Y Azzam, H Salem, A Seleim, A Abdelmajeed, M Abdou, N E Abosamak, M Al Sayed, F Ashoush, R Atta, E Elazzazy, M Elhoseiny, M Elnemr, M S Elqasabi, M E Elsayed Hewalla, I Elsherbini, E Essam, M Eweda, I Ghallab, E Hassan, M Ibrahim, M Metwalli, M Mourad, M S Qatora, M Ragab, A Sabry, H Saifeldin, M Saleh Mesbah Mohamed Elkaffas, A Samih, A Samir Abdelaal, S Shehata, K Shenit, D Attia, N Kamal, N Osman, A M Abbas, Has Abd Elazeem, M M Abdelkarem, S Alaa, A K Ali, A Ayman, M G Azizeldine, H Elkhayat, S M Elghazaly, F A Monib, M A Nageh, M M Saad, M Salah, M Shahine, E A Yousof, A Youssef, A Eldaly, M ElFiky, A Nabil, G Amira, I Sallam, M Sherief, A Sherif, A Abdelrahman, H Aboulkassem, G Ghaly, R Hamdy, A Morsi, H Salem, G Sherif, H Abdeldayem, I Abdelkader Salama, M Balabel, Y Fayed, A E Sherif, D Bekele, J Kauppila, E Sarjanoja, O Helminen, H Huhta, J H Kauppila, C Beyrne, L Jouffret, L Lugans, L Marie-Macron, E Chouillard, B De Simone, J Bettoni, S Dakpé, B Devauchelle, N Lavagen, S Testelin, S Boucher, R Breheret, A Gueutier, A Kahn, J KÜn-Darbois, A Barrabe, Z Lakkis, A Louvrier, S Manfredelli, P Mathieu, A Chebaro, V Drubay, M El Amrani, C Eveno, K Lecolle, G Legault, L Martin, G Piessen, F R Pruvot, S Truant, P Zerbib, Q Ballouhey, B Barrat, J Laloze, H Salle, A Taibi, J Usseglio, D Bergeat, A Merdrignac, Roy B Le, L O Perotto, A Scalabre, A Aimé, A Ezanno, B Malgras, P Bouche, S Tzedakis, E Cotte, O Glehen, V Kepenekian, J Lifante, G Passot, A D'Urso, E Felli, D Mutter, P Pessaux, B Seeliger, J Bardet, R Berry, G Boddaert, S Bonnet, E Brian, C Denet, D Fuks, D Gossot, M Grigoroiu, A Laforest, Y Levy-Zauberman, C Louis-Sylvestre, A Moumen, G Pourcher, A Seguin-Givelet, E Tribillon, E Duchalais, F Espitalier, C Ferron, O Malard, U Bork, M Distler, J Fritzmann, J Kirchberg, C Praetorius, C Riediger, J Weitz, T Welsch, P Wimberger, K Beyer, C Kamphues, J Lauscher, F N Loch, C Schineis, M Albertsmeier, M Angele, A Kappenberger, H Niess, T Schiergens, J Werner, R Becker, J Jonescheit, I Pergolini, D Reim, C Boeker, I Hakami, J Mall, P Liokatis, W Smolka, K Nowak, T Reinhard, F Hölzle, A Modabber, P Winnand, M Knitschke, P Kauffmann, S Wolfer, J Kleeff, K Lorenz, C Michalski, U Ronellenfitsch, R Schneider, E Bertolani, A Königsrainer, M W Löffler, M Quante, C Steidle, L ÜberrÜck, C Yurttas, C S Betz, J Bewarder, A Böttcher, S Burg, C Busch, M Gosau, A Heuer, J Izbicki, T O Klatte, D Koenig, N Moeckelmann, C Nitschke, M Priemel, R Smeets, U Speth, S Thole, F G Uzunoglu, T Vollkommer, N Zeller, M J Battista, K Gillen, A Hasenburg, S Krajnak, V Linz, R Schwab, K Angelou, D Haidopoulos, A Rodolakis, P Antonakis, K Bramis, L Chardalias, I Contis, N Dafnios, D Dellaportas, G Fragulidis, A Gklavas, M Konstadoulakis, N Memos, I Papaconstantinou, A Polydorou, T Theodosopoulos, A Vezakis, M I Antonopoulou, D K Manatakis, N Tasis, N Arkadopoulos, N Danias, P Economopoulou, P Kokoropoulos, A Larentzakis, N Michalopoulos, J Selmani, T Sidiropoulos, V Tsaousis, P Vassiliu, K Bouchagier, S Klimopoulos, D Paspaliari, G Stylianidis, K Baxevanidou, K Bouliaris, P Chatzikomnitsa, M Efthimiou, A Giaglaras, C Kalfountzos, G Koukoulis, A M Ntziovara, K Petropoulos, K Soulikia, I Tsiamalou, K Zervas, S Zourntou, I Baloyiannis, A Diamantis, E Gkrinia, J Hajiioannou, C Korais, O Koukoura, K Perivoliotis, A Saratziotis, C Skoulakis, D Symeonidis, K Tepetes, G Tzovaras, D Zacharoulis, V Alexoudi, K Antoniades, I Astreidis, P Christidis, D Deligiannidis, T Grivas, O Ioannidis, I Kalaitsidou, L Loutzidou, A Mantevas, D Michailidou, K Paraskevopoulos, S Politis, A Stavroglou, D Tatsis, I Tilaveridis, K Vahtsevanos, G Venetis, I Karaitianos, T Tsirlis, A Charalabopoulos, T Liakakos, E Mpaili, D Schizas, E Spartalis, A Syllaios, C Zografos, C Anthoulakis, C Christou, V Papadopoulos, A Tooulias, D Tsolakidis, G Tsoulfas, D Zouzoulas, E Athanasakis, E Chrysos, J Tsiaoussis, S Xenaki, E Xynos, K Futaba, M F Ho, S F Hon, Twc Mak, Ssm Ng, C C Foo, B Banky, N Suszták, M Aremu, A Canas-Martinez, O Cullivan, C Murphy, P Owens, L Pickett, L Akmenkalne, J Byrne, M Corrigan, C Cullinane, A Daly, C Fleming, P Jordan, S Killeen, N Lynch, A McCarthy, H Mustafa, S O'Brien, P O'Leary, Was Syed, L Vernon, D Callanan, L Huang, A Ionescu, P Sheahan, I Balasubramanian, M Boland, K Conlon, D Evoy, N Fearon, T Gallagher, J Geraghty, H Heneghan, N Kennedy, D Maguire, D McCartan, E W McDermott, R S Prichard, D Winter, D Alazawi, C Barry, T Boyle, W Butt, E M Connolly, N Donlon, C Donohue, B A Fahey, R Farrell, C Fitzgerald, J Kinsella, J O Larkin, P Lennon, P J Maguire, P Mccormick, B J Mehigan, H Mohan, T Nugent, H O'Sullivan, N Ravi, J V Reynolds, A Rogers, P Shokuhi, J Smith, L A Smith, C Timon, Y Bashir, G Bass, T Connelly, B Creavin, H Earley, J A Elliott, A Gillis, D Kavanagh, P Neary, J O'riordan, I S Reynolds, D Rice, P Ridgway, M Umair, M Whelan, P Carroll, C Collins, K Corless, L Finnegan, A Fowler, A Hogan, M Kerin, A Lowery, P McAnena, K McKevitt, K Nizami, É Ryan, A Samy, J C Coffey, R Cunningham, M Devine, D Nally, C Peirce, S Tormey, N Hardy, P Neary, S O'Malley, M Ryan, S Macina, N M Mariani, E Opocher, A Pisani Ceretti, F Ferrari, F Odicino, E Sartori, C Cotsoglou, S Granieri, F Bianco, A Camillo, M Colledan, S Tornese, M F Zambelli, G Bissolotti, S Fusetti, F Lemma, M V Marino, A Mirabella, G Vaccarella, C Agostini, G Alemanno, I Bartolini, C Bergamini, A Bruscino, C Checcucci, R De Vincenti, A Di Bella, M Fambrini, L Fortuna, G Maltinti, P Muiesan, F Petraglia, P Prosperi, M N Ringressi, M Risaliti, F Sorbi, A Taddei, R Tucci, C Bassi, L Bortolasi, T Campagnaro, L Casetti, M De Pastena, A Esposito, M Fontana, A Guglielmi, L Landoni, G Malleo, G Marchegiani, S Nobile, S Paiella, C Pedrazzani, S Rattizzato, A Ruzzenente, R Salvia, G Turri, M Tuveri, P Bellora, G D'Aloisio, M Ferrari, E Francone, S Gentilli, H Nikaj, M Bianchini, M Chiarugi, F Coccolini, G Di Franco, N Furbetta, D Gianardi, S Guadagni, L Morelli, M Palmeri, D Tartaglia, G Anania, P Carcoforo, M Chiozza, A De Troia, M Koleva Radica, M Portinari, M G Sibilla, A Urbani, N Fabbri, C V Feo, S Gennari, S Parini, E Righini, L Ampollini, L Bellanti, M Bergonzani, G Bertoli, G Bocchialini, G D'Angelo, D Lanfranco, L Musini, T Poli, G P Santoro, A Varazzani, L Aguzzoli, G Borgonovo, C Castro Ruiz, S Coiro, G Falco, V D Mandato, V Mastrofilippo, M T Montella, V Annessi, M Zizzo, U Grossi, S Novello, M Romano, S Rossi, G Zanus, G Esposito, F Frongia, A Pisanu, M Podda, C Belluco, A Lauretta, G Montori, L Moras, M Olivieri, F Bussu, A G Carta, M L Cossu, P Cottu, A Fancellu, C F Feo, G C Ginesu, G Giuliani, M Madonia, T Perra, A Piras, A Porcu, D Rizzo, A M Scanu, A Tedde, M Tedde, P Delrio, D Rega, G Badalamenti, G Campisi, A Cordova, M Franza, G Maniaci, G Rinaldi, F Toia, M Calabrò, F Farnesi, E G Lunghi, A Muratore, N S Pipitone Federico, F Bàmbina, G D'Andrea, P Familiari, V Picotti, G De Palma, G Luglio, G Pagano, F P Tropeano, L Baldari, G A Beltramini, L Boni, E Cassinotti, A Gianni, L Pignataro, S Torretta, C Abatini, M Baia, D Biasoni, G Bogani, P Cadenelli, V Capizzi, Spb Cioffi, D Citterio, L V Comini, M Cosimelli, M Fiore, S Folli, M Gennaro, L Giannini, A Gronchi, M Guaglio, A Macchi, F Martinelli, V Mazzaferro, A Mosca, S Pasquali, C Piazza, F Raspagliesi, L Rolli, R Salvioni, G Sarpietro, C Sarre, L Sorrentino, A Agnes, S Alfieri, F Belia, A Biondi, V Cozza, A D'Amore, D D'Ugo, V De Simone, A Fagotti, G Gasparini, L Gordini, F Litta, C P Lombardi, L Lorenzon, A A Marra, F Marzi, A Moro, A Parello, E Perrone, R Persiani, C Ratto, F Rosa, G Saponaro, G Scambia, O Scrima, G Sganga, R Tudisco, A Belli, V Granata, F Izzo, R Palaia, R Patrone, F M Carrano, M M Carvello, A De Virgilio, F Di Candido, F Ferreli, F Gaino, G Mercante, V Rossi, A Spinelli, G Spriano, D M Donati, T Frisoni, E Palmerini, A Aprile, F Barra, P Batistotti, S Ferrero, P Fregatti, S Scabini, M Sparavigna, E Asti, D Bernardi, L Bonavina, A Lovece, L Adamoli, M Ansarin, S Cenciarelli, F Chu, R De Berardinis, U Fumagalli Romario, F Mastrilli, G Pietrobon, M Tagliabue, E Badellino, A Ferrero, R Massobrio, A De Manzoni Garberini, P Federico, P Maida, E Marra, G Marte, A Petrillo, T Tammaro, A Tufo, M Berselli, G Borroni, E Cocozza, L Conti, M Desio, L Livraghi, V Quintodei, A Rizzi, A Zullo, C Baldi, C Corbellini, G M Sampietro, P Cellerino, E Baldini, P Capelli, L Conti, S M Isolani, M Ribolla, A Bondurri, F Colombo, L Ferrario, C Guerci, A Maffioli, T Armao, M Ballabio, P Bisagni, A Gagliano, M Longhi, M Madonini, P PizziCni, A M Baietti, M Biasini, P Maremonti, F Neri, G M Prucher, S Ricci, F Ruggiero, A G Zarabini, R Barmasse, S Mochet, L Morelli, A Usai, F Bianco, P Incollingo, S Mancini, L Marino Cosentino, A Sagnotta, R Fruscio, T Grassi, L C Nespoli, N Tamini, A Anastasi, B Bartalucci, A Bellacci, G Canonico, L Capezzuoli, C Di Martino, P Ipponi, C Linari, M Montelatici, T Nelli, G Spagni, L Tirloni, A Vitali, E Abate, M Casati, T Casiraghi, L Laface, M Schiavo, A Arminio, A Cotoia, V Lizzi, F Vovola, R Vergari, S D'Ugo, N Depalma, M G Spampinato, P Bartolucci, G Brachini, P Bruzzaniti, A Chiappini, V Chiarella, F Ciccarone, P M Cicerchia, B Cirillo, G De Toma, A Di Bartolomeo, E Fiori, G B Fonsi, G Franco, A Frati, M Giugliano, I Iannone, F La Torre, P Lapolla, C Leonardo, G Marruzzo, S Meneghini, A Mingoli, D Ribuffo, M Salvati, A Santoro, P Sapienza, A K Scafa, L Simonelli, M Zambon, G T Capolupo, F Carannante, M Caricato, G Mascianà, E Mazzotta, A Gattolin, M Migliore, R Rimonda, D Sasia, E Travaglio, 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La Regina, F Mongelli, M Chevallay, O Dwidar, E Gialamas, M Sauvain, F Klenke, A Kollàr, C Kurze, M Adamina, T Bächler, A S Crugnale, M Giardini, L Guglielmetti, G Peros, F Solimene, A Aghayeva, I Hamzaoglu, I Sahin, E Akaydin, Z Aliyeva, E Aytac, B Baca, O DÜlgeroğlu, V Ozben, B B Ozmen, C Uras, A E Arikan, I A Bilgin, B Bozkirli, G O Ceyhan, H Kara, T Karahasanoglu, C Uras, H Celik, M M Meydanli, H Akilli, A Ayhan, E Kuscu, M A Onan, U Akgor, H A Dincer, T Erol, M Gultekin, N Orhan, N Ozgul, M C Salman, B Soyak, A Alhamed, S ErgÜn, M F OZcelik, A N Sanli, S S Uludag, M Velidedeoglu, A K Zengin, M A Bozkurt, Y Kara, A Kocatas, B Cimenoglu, R Demirhan, K Saracoglu, I F Azamat, E Balik, D Bugra, B Giray, C B Kulle, C Taskiran, D Vatansever, K Gözal, S A GÜler, H Köken, O C Tatar, N Z Utkan, A Yildirim, E YÜksel, E Akin, F Altintoprak, Z Bayhan, G Cakmak, R Çapoglu, F Çelebi, H Demir, E Dikicier, N Firat, E GönÜllÜ, M B Kamburoglu, B Kocer, I F KÜçÜk, B Mantoglu, E Çolak, G O Kucuk, M S Uyanik, B Göksoy, E Bozkurt, B Citgez, M Mihmanli, M Tanal, G Yetkin, M Akalin, C Arican, E K Avci, C Aydin, S Demirli Atici, M Emiroglu, T Kaya, E Kebabçi, G Kilinc, Y Kirmizi, H Ogucu, S Salimoglu, I Sert, C Tugmen, K Tuncer, G Uslu, D Yesilyurt, E Karaman, A Kolusari, A Yildiz, O Benson, H Lule, J Agilinko, A Ahmeidat, M Barabasz, M Bekheit, L K Cheung, T Colloc, W Cymes, M Elhusseini, G Gradinariu, A Hannah, B S Kamera, G Mignot, S Shaikh, P Sharma, I Abu-Nayla, A Agrawal, A Al-Mohammad, S Ali, J Ashcroft, A Azizi, O Baker, A Balakrishnan, M Byrne, A Colquhoun, A Cotter, P Coughlin, R J Davies, A Durrani, M Elshaer, S Fordington, P Forouhi, F Georgiades, H Grimes, A Habeeb, V Hudson, P Hutchinson, E Irune, A Jah, D Z Khan, A Kolias, H Kyriacou, B Lamb, S Liau, L Luke, R Mahmoud, R Mannion, L Masterson, C G Mitrofan, M Mohan, A Morris, S Murphy, R O'Neill, S Price, J Pushpa-Rajah, W Raby-Smith, J Ramzi, S Rooney, T Santarius, A Singh, G D Stewart, X S Tan, A Townson, E Tweedle, C Walker, S Waseem, S Yordanov, T Jones, A Kattakayam, C Loh, R Lunevicius, S Pringle, A Schache, R Shaw, A Sheel, C Rossborough, D Angelou, M Choynowski, B McAree, A McCanny, D Neely, G Tutoveanu, S Ahad, Mfi De La Cruz Monroy, F Mosley, V Oktseloglou, A Alanbuki, M Patel, A Shabana, E Perera, D Raveendran, K Ravi-Shankar, J Thiruchelvam, L Arrowsmith, W Campbell, T Grove, C Kontovounisios, O Warren, P Rolland, A Aggarwal, S Brown, C Jelley, N Neal, R Clifford, N Eardley, E Krishnan, N Manu, E Martin, S Roy Mahapatra, O L Serevina, C Smith, D Vimalachandran, M Bordenave, R Houston, G Putnam, A Robson, H Tustin, K Emslie, P L Labib, A Marchbank, D Miller, G Minto, J Natale, H Nwinee, P Panahi, L Rogers, A Abubakar, M M Akhter Rahman, E Chan, Kyk Ko, H O'Brien, K Sasapu, H Woodun, R Inglis, H J Ng, A De Gea Rico, N Ghazali, J Lambert, G Markose, S Math, I Sarantitis, D Shrestha, A Sultana, M Taggarsi, S Timbrell, O P Vaz, L Vitone, A Day, H Dent, M Fahim, S Waheed, A Hunt, N Laskar, A Gupta, J Steinke, S Thrumurthy, E Massie, K McGivern, D Rutherford, M Wilson, J Hardie, S Kazzaz, S Handa, M Kaushal, A Kler, P Patel, J Redfern, S Tezas, Y Aawsaj, S Amonkar, C Barry, L Blackwell, D Blake, J Carter, H Emerson, A Fisher, M Katory, P Korompelis, W McCormick, A Mustafa, L Pearce, N Ratnavelu, R Reehal, L Kretzmer, L Lalou, B Manku, I Parwaiz, J Stafford, M Abdelkarim, A Asqalan, T Gala, S Ibrahim, A Maw, R Mithany, R Morgan, G Sundaram Venkatesan, K Ang, E J Caruana, M F Chowdhry, A Mohammad, A Nakas, S Rathinam, M Boal, O Brown, S Dwerryhouse, S Higgs, A Vallance, E Boyd, V Irvine, A Kirk, G Bakolas, A Boulton, A Chandock, T Khan, M Kumar, P Agoston, A Bille, B Challacombe, S Fraser, K Harrison-Phipps, J King, G Mehra, L Mills, M Najdy, R Nath, L Okiror, J Pilling, V Rizzo, T Routledge, A Sayasneh, L Stroman, A Wali, M Fehervari, C Fotopoulou, N Habib, S Hamrang-Yousefi, Z Jawad, L Jiao, M Pai, J Ploski, P Rajagopal, S Saso, M Sodergren, D Spalding, S Laws, C Hardie, C McNaught, R Alam, A Budacan, J Cahill, M Kalkat, S Karandikar, L Kenyon, D Naumann, A Patel, J Ayorinde, T Chase, T Cuming, A Ghanbari, L Humphreys, S Tayeh, A Aboelkassem Ibrahim, R Bichoo, H Cao, Akw Chai, J Choudhury, C Evans, H Fitzjohn, H Ikram, M Langstroth, M Loubani, A McMillan, S Nazir, Ssa Qadri, A Robinson, E Ross, T Sehgal, A Wilkins, J Dixon, J Dunning, K Freystaetter, M Jha, S Lester, A Madhavan, S V Thulasiraman, Y Viswanath, T Curl-Roper, C Delimpalta, Ccl Liao, V Velchuru, E Westwood, E Belcher, G Bond-Smith, S Chidambaram, F Di Chiara, K Fasanmade, L Fraser, H Fu, M Ganau, S Gore, J Graystone, D Jeyaretna, H Khatkar, M Lami, M Maher, S Mastoridis, R Mihai, R Piper, S Prabhu, Obf Risk, U Selbong, K Shah, R Smillie, H Soleymani Majd, S Sravanam, D Stavroulias, G D Tebala, M Vatish, C Verberne, K Wallwork, S Winter, M I Bhatti, H Boyd-Carson, E Elsey, E Gemmill, P Herrod, M Jibreel, E Lenzi, T Saafan, D Sapre, T Sian, N Watson, A Athanasiou, G Bourke, L Bradshaw, A Brunelli, J Burke, P Coe, F Costigan, H Elkadi, M Ho, J Johnstone, A Kanatas, V Kantola, A Kaufmann, A Laios, S Lam, E MacInnes, S Munot, C Nahm, M Otify, C Pompili, I Smith, G Theophilou, G Toogood, R Wade, D Ward, C West, S Annamalai, C Ashmore, A Boddy, T Hossain, A Kourdouli, A Gvaramadze, A Jibril, L Prusty, D Thekkinkattil, A Harky, M Shackcloth, A Askari, C Chan, N Cirocchi, S Kudchadkar, K Patel, J Sagar, S Shaw, R Talwar, M Abdalla, R Edmondson, O Ismail, D Jones, K Newton, N Stylianides, A Aderombi, U Andaleeb, O Bajomo, K Beatson, W Garrett, M Mehmood, V Ng, R Al-Habsi, G S Divya, B Keeler, B Al-Sarireh, R Egan, R Harries, A Henry, M Kittur, Z Li, K Parkins, F Soliman, N Spencer, D Thompson, C Burgess, C Gemmell, C Grieco, M Hollyman, L Hunt, J Morrison, S Ojha, N Ryan, F Abbadessa, S Barnard, C Chan, N Dawe, J Hammond, Ali F Mahmoud, I McPherson, C Mellor, J Moir, S Pandanaboyana, J Powell, B Rai, A Rogers, C Roy, A Sachdeva, C Saleh, S Tingle, T Williams, J Manickavasagam, C McDonald, N McGrath, N McSorley, K Ragupathy, L Ramsay, A Solth, O Kakisi, K Seebah, I Shaikh, L Sreedharan, M Youssef, J Shah, P Ameerally, N McLarty, S Mills, A Shenfine, K Sahnan, J Abu, E Addae-Boateng, D Bratt, L Brock, N Burnside, S Cadwell-Sneath, K Gajjar, C Gan, C Grundy, K Hallam, K Hassell, M Hawari, A Joshi, H Khout, K Konstantinidi, Rxn Lee, D Nunns, R Schiemer, T Walton, H Weaver, L Whisker, K Williamson, J McVeigh, R Myatt, M A Williams, R Kaur, E Leung, S Sundar, M Michel, S Patil, S Ravindran, J Sarveswaran, L Scott, M Edmond, E King, M Almond, A Bhangu, O Breik, L D Cato, A Desai, S Ford, E Griffiths, M Idle, M Kamal, A Kisiel, R Kulkarni, Jkc Mak, T Martin, P Nankivell, A Parente, S Parmar, A M Pathanki, L Phelan, P Praveen, S Saeed, N Sharma, J Singh, F Tirotta, D Vijayan, A Geddes, J McCaul, J McMahon, A H Khan, F Khan, A Mansuri, S Mukherjee, M Patel, M Sarigul, S Singh, K L Tan, A Woodham, A Adiamah, H Brewer, A Chowdhury, J Evans, D Humes, J Jackman, A Koh, C Lewis-Lloyd, O Oyende, J Reilly, D Worku, P Cool, G Cribb, K Shepherd, C Bisset, S Moug, N Elson, G Faulkner, P Saleh, C Underwood, G Brixton, L Findlay, T Klatte, A Majkowska, J Manson, R Potter, A Bhalla, Z Chia, P Daliya, A Goyal, E Grimley, A Hamad, A Kumar, F L Malcolm, E Theophilidou, J Bowden, N Campain, I Daniels, C Evans, G Fowler, J John, L Massey, F McDermott, J McGrath, A McLennan, M Ng, J Pascoe, N Rajaretnam, S Bulathsinhala, B Davidson, G Fusai, C Hidalgo Salinas, N Machairas, T Pissanou, J M Pollok, D A Raptis, F Soggiu, H Tzerbinis, S E Xyda, A Beamish, E Davies, R Foulkes, D Magowan, H Nassa, R Ooi, C Price, L Smith, F Solari, A Tang, G Williams, Y Al-Tamimi, A Bacon, N Beasley, D Chew, M Crank, N Ilenkovan, M Macdonald, B Narice, O Rominiyi, A Thompson, I Varley, T Drake, E Harrison, G Linder, J Mayes, R McGregor, R Skipworth, V Zamvar, E Davies, P Hawkin, T Raymond, O Ryska, R Baron, D Dunne, S Gahunia, C Halloran, N Howes, R McKinney, F McNicol, J Russ, P Szatmary, J R Tan, A Thomas, P Whelan, A Anzak, A Banerjee, O Fuwa, F Hughes, J D Jayasinghe, C Knowles, H Kocher, I Leal Silva, F S Ledesma, A Minicozzi, L Navaratne, R Rahman, R Ramamoorthy, C Sohrabi, M Thaha, B Thakur, M Venn, V Yip, R Baumber, J Parry, S Evans, L Jeys, G Morris, M Parry, J Stevenson, N Ahmadi, G Aresu, Z M Barrett-Brown, A S Coonar, H Durio Yates, D Gearon, J Hogan, M King, A Peryt, I S Pradeep, C Smith, M Adishesh, R Atherton, K Baxter, M Brocklehurst, M Chaudhury, N Krishnamohan, J McAleer, G Owens, E Parkin, P Patkar, I Phang, A Aladeojebi, M Ali, B Barmayehvar, A Gaunt, M Gowda, E Halliday, M Kitchen, F Mansour, M Thomas, D Zakai, N Abbassi-Ghadi, H Assalaarachchi, A Currie, M Flavin, A Frampton, M Hague, C Hammer, J Hopper, J Horsnell, S Humphries, A Kamocka, T K Madhuri, S Preston, P Singh, J Stebbing, A Tailor, D Walker, F Aljanadi, M Jones, P Mhandu, C O'Donnell, R Turkington, Z Al-Ishaq, S Bhasin, A S Bodla, A Burahee, A Crichton, R Fossett, N Pigadas, S Pickford, E Rahman, D Snee, R Vidya, N Yassin, F Colombo, D Fountain, M T Hasan, K Karabatsou, R Laurente, O Pathmanaban, A Al-Mukhtar, S Brown, J Edwards, A Giblin, C Kelty, M Lee, G Lye, T Newman, A Sharkey, C Steele, N Sureshkumar Shah, E Whitehall, R Athwal, A Baker, L Jones, C Konstantinou, S Ramcharan, S Singh, J Vatish, R Wilkin, M Ethunandan, G K Sekhon, H Shields, R Singh, F Wensley, S Lawday, A Lyons, T Abbott, S Anwar, K Ghufoor, C Sohrabi, E Chung, R Hagger, A Hainsworth, A Karim, H Owen, A Ramwell, K Williams, C Baker, A Davies, J Gossage, M Kelly, W Knight, J Hall, G Harris, G James, C Kang, D J Lin, A D Rajgor, T Royle, R Scurrah, B Steel, L J Watson, D Choi, R Hutchison, A Jain, V Luoma, H Marcus, R May, A Menon, B Pramodana, L Webber, I A Aneke, P Asaad, B Brown, J Collis, S Duff, A Khan, F Moura, B Wadham, H Warburton, T Elmoslemany, M Jenkinson, C Millward, R Zakaria, S Mccluney, C Parmar, S Shah, J Allison, M S Babar, B Collard, S Goodrum, K Lau, A Patel, R Scott, E Thomas, H Whitmore, D Balasubramaniam, B Jayasankar, S Kapoor, A Ramachandran, A Elhamshary, Smb Imam, K Kapriniotis, V Kasivisvanathan, J Lindsay, S Rakhshani-Moghadam, N Beech, M Chand, L Green, N Kalavrezos, H Kiconco, R McEwen, C Schilling, D Sinha, J Pereca, J Singh, S Chopra, D Egbeare, R Thomas, T Combellack, Sef Jones, M Kornaszewska, M Mohammed, A Sharma, G Tahhan, V Valtzoglou, J Williams, P Eskander, K Gash, L Gourbault, M Hanna, T Maccabe, C Newton, J Olivier, S Rozwadowski, E Teh, D West, H Al-Omishy, M Baig, H Bates, G Di Taranto, K Dickson, N Dunne, C Gill, D Howe, D Jeevan, A Khajuria, K Martin-Ucar AMcEvoy, P Naredla, V Ng, S Robertson, M Sait, D R Sarma, S Shanbhag, T Shortland, S Simmonds, J Skillman, N Tewari, G Walton, M A Akhtar, A Brunt, J McIntyre, K Milne, M M Rashid, A Sgro, K E Stewart, A Turnbull, M Aguilar Gonzalez, S Talukder, C Boyle, D Fernando, K Gallagher, A Laird, D Tham, M Bath, P Patki, C Sohrabi, C Tanabalan, T Arif, C Magee, T Nambirajan, S Powell, R Vinayagam, I Flindall, A Hanson, V Mahendran, S Green, M Lim, L MacDonald, V Miu, L Onos, K Sheridan, R Young, F Alam, O Griffiths, C Houlden, R Jones, V S Kolli, A K Lala, S Leeson, R Peevor, Z Seymour, L Chen, E Henderson, A Loehrer, K Brown, D Fleming, A Haynes, C Heron, C Hill, H Kay, E Leede, K McElhinney, K Olson, E C Osterberg, C Riley, P Srikanth, M Thornhill, D Blazer, G DiLalla, E S Hwang, W Lee, M Lidsky, J Plichta, L Rosenberger, R Scheri, K Shah, K Turnage, J Visgauss, S Zani, J Farma, J Clark, D Kwon, E Etchill, H E Gabre-Kidan AJenny, A Kent, M Ladd, C Long, H Malapati, A Margalit, S Rapaport, J Rose, K Stevens, L Tsai, D Vervoort, P Yesantharao, A Dehal, D Klaristenfeld, K Huynh, L Brown, I Ganly, J Mullinax, N Gusani, J Hazelton, J Maines, J S Oh, A Ssentongo, P Ssentongo, M Azam, A Choudhry, W Marx, J Fleming, A Fuson, J Gigliotti, A Ovaitt, Y Ying, M K Abel, V Andaya, K Bigay, M A Boeck, L Chen, H Chern, C Corvera, I El-Sayed, A Glencer, P Ha, Bcs Hamilton, C Heaton, K Hirose, D M Jablons, K Kirkwood, L Z Kornblith, J R Kratz, R Lee, P N Miller, E Nakakura, B Nunez-Garcia, R O'Donnell, D Ozgediz, P Park, B Robinson, A Sarin, B Sheu, M Varma, K Wai, R Wustrack, M J Xu, D Beswick, J Goddard, J Manor, J Song, T Fullmer, C Gaskill, N Gross, K Kiong, C L Roland, S N Zafar, M Abdallah, A Abouassi, M Almasri, G Kulkarni, H Marwan, M Mehdi, S Aoun, V S Ban, H H Batjer, J Caruso, D Abbott, A Acher, T Aiken, J Barrett, E Foley, P Schwartz, S N Zafar, A Hawkins, A Maiga, J Laufer, S Scasso

Subjects
Aged, 80 and over, Male, Critical Care, SARS-CoV-2, International Cooperation, COVID-19, Middle Aged, Cohort Studies, Logistic Models, Postoperative Complications, Elective Surgical Procedures, Neoplasms, Outcome Assessment, Health Care, Humans, Female, Epidemics, Aged
Abstract

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks.

Published
2021

12. El enfoque adaptativo del confort térmico en Sevilla = The adaptive approach to thermal comfort in Seville.

Author

Sánchez García, D., Sánchez-Guevara Sánchez, Carmen, Rubio Bellido, C., Sánchez García, D., Sánchez-Guevara Sánchez, Carmen, and Rubio Bellido, C.

Abstract

Aunque los estándares de confort en los edificios de oficinas acondicionados con medios mecánicos se han estudiado ampliamente a través de la norma ISO 7730 basada en los estudios de Fanger, todavía no existe un enfoque consensuado para el confort térmico en las viviendas. Muchas de esas viviendas, que componen un bloque, se han construido antes de que se introdujeran normas de ahorro de energía, por lo que existe un alto consumo energético que tiene un efecto sobre el medio ambiente y la economía. A través de los años, el modelo de confort térmico más utilizado se basa en un modelo estático, en el que el ser humano es similar a un receptor pasivo de los estímulos térmicos, mientras que el modelo adaptativo deja en manos del ocupante hacer algunos ajustes y lograr confort a través de acciones y de la adaptación psicológica. La presente investigación tiene como objetivo estudiar los límites de confort adaptativo en una vivienda similar a la mencionada anteriormente, con el fin de regular el uso de aire acondicionado y calefacción, y además reducir el exceso de consumo de energía.

Published
2016

21. Unravelling the Antifibrinolytic Mechanism of Action of the 1,2,3-Triazole Derivatives.

Author

Rabadà Y, Bosch-Sanz O, Biarnés X, Pedreño J, Caveda L, Sánchez-García D, Martorell J, and Balcells M

Subjects
Humans, Molecular Dynamics Simulation, Plasminogen metabolism, Plasminogen chemistry, Fibrinolysis drug effects, Triazoles chemistry, Triazoles pharmacology, Antifibrinolytic Agents pharmacology, Antifibrinolytic Agents chemistry, Tranexamic Acid pharmacology, Tranexamic Acid chemistry
Abstract

A new family of antifibrinolytic drugs has been recently discovered, combining a triazole moiety, an oxadiazolone, and a terminal amine. Two of the molecules of this family have shown activity that is greater than or similar to that of tranexamic acid (TXA), the current antifibrinolytic gold standard, which has been associated with several side effects and whose use is limited in patients with renal impairment. The aim of this work was to thoroughly examine the mechanism of action of the two ideal candidates of the 1,2,3-triazole family and compare them with TXA, to identify an antifibrinolytic alternative active at lower dosages. Specifically, the antifibrinolytic activity of the two compounds ( 1 and 5 ) and TXA was assessed in fibrinolytic isolated systems and in whole blood. Results revealed that despite having an activity pathway comparable to that of TXA, both compounds showed greater activity in blood. These differences could be attributed to a more stable ligand-target binding to the pocket of plasminogen for compounds 1 and 5 , as suggested by molecular dynamic simulations. This work presents further evidence of the antifibrinolytic activity of the two best candidates of the 1,2,3-triazole family and paves the way for incorporating these molecules as new antifibrinolytic therapies.

Published
2024
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22. 1,2,3-Triazole Derivatives as Novel Antifibrinolytic Drugs.

Author

Bosch-Sanz O, Rabadà Y, Biarnés X, Pedreño J, Caveda L, Balcells M, Martorell J, and Sánchez-García D

Subjects
Humans, Molecular Docking Simulation, Fibrinolysis, Aminocaproic Acid pharmacology, Aminocaproic Acid therapeutic use, Triazoles pharmacology, Antifibrinolytic Agents pharmacology, Tranexamic Acid pharmacology
Abstract

Fibrinolysis is a natural process that ensures blood fluidity through the removal of fibrin deposits. However, excessive fibrinolytic activity can lead to complications in different circumstances, such as general surgery or severe trauma. The current antifibrinolytic drugs in the market, aminocaproic acid (EACA) and tranexamic acid (TXA), require high doses repetitively to maintain their therapeutic effect. These high doses are related to a number of side effects such as headaches, nasal symptoms, or gastrointestinal discomfort and severely limit their use in patients with renal impairment. Therefore, the discovery of novel antifibrinolytics with a higher specificity and lower dosage could vastly improve the applicability of these drugs. Herein, we synthesized a total of ten compounds consisting of a combination of three key moieties: an oxadiazolone, a triazole, and a terminal amine. The IC 50 of each compound was calculated in our clot lysis assays, and the best candidate ( 1 ) provided approximately a 2.5-fold improvement over the current gold standard, TXA. Molecular docking and molecular dynamics were used to perform a structure-activity relationship (SAR) analysis with the lysine binding site in the Kringle 1 domain of plasminogen. This analysis revealed that 1,2,3-triazole was crucial for the activity, enhancing the binding affinity through pi-pi stacking and polar interactions with Tyr72. The results presented in this work open the door to further investigate this new family as potential antifibrinolytic drugs.

Published
2022
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23. Temperature or competition: Which has more influence on Mediterranean ant communities?

Author

Sánchez-García D, Cerdá X, and Angulo E

Subjects
Animals, Ecosystem, Forests, Humans, Species Specificity, Temperature, Ants
Abstract

Temperature and competition are two of the main factors determining ant community assemblages. Temperature may allow species to forage more or less efficiently throughout the day (in accordance with the maximum activity temperature of each species). Competition can be observed and quantified from species replacements occurring during resource exploitation. We studied the interspecific competitive interactions of ant communities from the Doñana Biological Reserve (southern Spain). Ants were sampled from pitfall traps and baits in three habitats with contrasted vegetation physiognomy (savin forest, pine forest, and dry scrubland). We measured the temperature during the competitive interactions between species and created a thermal competition index (TCI) to assess the relative contribution of temperature and numerical dominance to the competitive outcomes. Temperature had unequal effects on ant activity in each type of habitat, and modulated competitive interactions. The TCI showed that a species' success during pair interactions (replacements at baits) was driven by the proportion of workers between the two competing species and by the species-specific effect of temperature (how advantageous the temperature change is for each species during bait replacement). During competitive interactions, the effect of temperature (higher values of TCI) and numeric supremacy (higher worker proportion) gave higher success probabilities. Interspecific competitive relationships in these Mediterranean ant communities are habitat dependent and greatly influenced by temperature., Competing Interests: The authors have declared that no competing interests exist.

Published
2022
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24. Effects of Sex, Age and Height on Symphysis-Ischial Spine Distance Measured on a Pelvic CT.

Author

Sánchez García D, Aguado Del Hoyo A, Sánchez Pérez M, Larroca SG, Ruiz Martín Y, Gordillo Gutiérrez I, Arribas CB, Alvarez-Mon M, Ortega MA, and De Leon-Luis J

Abstract

Objective: To examine the influence of age, sex and height on the symphysis-ischial spine distance (SID) measured on pelvic Computed tomography (CT)images in subjects of reproductive age, and to determine the interobserver reproducibility. This measurement (SID) is of great importance because the use of intrapartum ultrasound is based on the assumption of a specific value (30 mm) of such a measurement., Methods: This was a cross-sectional descriptive study in which SID was measured in subjects aged 20 to 44 years who had been scheduled for pelvic CT at our centre from January 2018 to May 2021 for different reasons. Radiographic measurements of the pelvis were obtained through the multiplanar reconstruction of the CT image. The images obtained from all of the participants were independently assessed by three senior radiologists, and the SID measurements made by each one were blinded from those of the remaining observers. Correlations between the SID and patient age, height and sex were analyzed by univariate and multivariate linear regression., Results: The mean SID for 87 of the enrolled participants (45 women, 42 men) was 28.2 ± 6.25 mm. Among the observers, the mean difference in this distance was 1 to 2 mm, and was scarcely related to measurement size, with agreement being greater than 70%. The mean SID was significantly related to sex and height (SID = -24.9 - 6.51 × sex (0 or 1) + 0.34 × height (cm); p = 0.01; sex equals 1 for a man and 0 for a woman), such that it was a mean of 2.5 mm greater in women than men (29.50 mm vs. 26.99 mm)., Conclusion: Measurements of SID on CT images show good interobserver reproducibility, and are related to sex and height.

Published
2022
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25. Nanoparticles for Triple Drug Release for Combined Chemo- and Photodynamic Therapy.

Author

Martínez-Edo G, Xue EY, Ha SYY, Pontón I, González-Delgado JA, Borrós S, Torres T, Ng DKP, and Sánchez-García D

Subjects
Doxorubicin, Drug Delivery Systems, Drug Liberation, Humans, Silicon Dioxide, Nanoparticles, Photochemotherapy
Abstract

A pH-responsive drug delivery system (DDS) based on mesoporous silica nanoparticles (MSNs) has been prepared for the delivery of three anticancer drugs with different modes of action. The novelty of this system is its ability to combine synergistic chemotherapy and photodynamic therapy. A photoactive conjugate of a phthalocyanine (Pc) and a topoisomerase I inhibitor (topo-I), namely camptothecin (CPT), linked by a poly(ethylene glycol) (PEG) chain has been synthesized and then loaded into the mesopores of MSNs. Doxorubicin (DOX), which is a topoisomerase II inhibitor (topo-II), has also been covalently anchored to the outer surface of the MSNs through a dihydrazide PEG linker. In the acidic environment of tumor cells, selective release of the three drugs takes place. In vitro studies have demonstrated the endocytosis of the system into HeLa and HepG2 cells, and the subsequent release of the three drugs into the cytoplasm and nucleus. Furthermore, the cytotoxic effect of DOX, CPT and Pc has been assessed in vitro before and upon light irradiation., (© 2021 Wiley-VCH GmbH.)

Published
2021
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26. Revising Protein Corona Characterization and Combining ITC and Nano-DSC to Understand the Interaction of Proteins With Porous Nanoparticles.

Author

Balmori A, Sandu R, Gheorghe D, Botea-Petcu A, Precupas A, Tanasescu S, Sánchez-García D, and Borrós S

Abstract

The exposure of nanoparticles (NPs) to biological fluids leads to the formation of a protein coating that is known as protein corona (PC). Since PC formation is influenced by the physicochemical properties of the nanoparticles, the understanding of the interplay of the factors that participate in this process is crucial for the development of nanomaterials as cell-targeted delivery vehicles. In general, it is accepted that the PC formation is a complex and dynamic process, which depends on the composition of the medium and the properties of the NP mainly size, shape, and superficial charge. Interestingly, although the interaction between the protein and the NP is essentially a superficial phenomenon, the influence of the roughness of the nanoparticle surface has been scarcely studied. In this work, the influence of superficial roughness and porosity has been studied with the aid of nanodifferential scanning calorimetry (nano-DSC) and isothermal titration calorimetry (ITC) using mesoporous silica nanoparticles (MSNs) as an NP model. The interaction process of the proteins with the NP surface was analyzed by ITC measurements, while the stability and denaturation of the proteins was monitored by nano-DSC. Thanks to the complementarity of these two techniques, a more complete insight into the PC formation on the pores has been accomplished., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Balmori, Sandu, Gheorghe, Botea-Petcu, Precupas, Tanasescu, Sánchez-García and Borrós.)

Published
2021
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27. Preparation and Applications of Organo-Silica Hybrid Mesoporous Silica Nanoparticles for the Co-Delivery of Drugs and Nucleic Acids.

Author

Pontón I, Martí Del Rio A, Gómez Gómez M, and Sánchez-García D

Abstract

Combination therapies rely on the administration of more than one drug, with independent mechanisms of action, aiming to enhance the efficiency of the treatment. For an optimal performance, the implementation of such therapies requires the delivery of the correct combination of drugs to a specific cellular target. In this context, the use of nanoparticles (NP) as platforms for the co-delivery of multiple drugs is considered a highly promising strategy. In particular, mesoporous silica nanoparticles (MSN) have emerged as versatile building blocks to devise complex drug delivery systems (DDS). This review describes the design, synthesis, and application of MSNs to the delivery of multiple drugs including nucleic acids for combination therapies.

Published
2020
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28. Analysing natural ventilation to reduce the cooling energy consumption and the fuel poverty of social dwellings in coastal zones.

Author

Bienvenido-Huertas D, Sánchez-García D, and Rubio-Bellido C

Abstract

In southern European countries, summer temperatures could contribute to a high cooling energy consumption. Family units with fewer economic resources living in social dwellings could suffer from fuel poverty if they want to use air conditioning systems. Otherwise, they could face discomfort hours because of a natural ventilation without clear control criteria. This study analyses quantitatively and qualitatively the possibilities of natural ventilation through mixed-mode and the possibility of reducing fuel poverty for family units living in social dwellings. For this purpose, the application of a natural ventilation approach was analysed through an adaptive behaviour based on EN 16798-1: 2019. A case study of 51 social dwellings was analysed by using various operation hypothesis between 2015 and 2019. The results showed the potential of using mixed-mode approaches based on the categories from EN 16798-1:2019 to achieve savings in the energy consumption and to remove cases of fuel poverty in low-income families. Likewise, surveys in which families living in these cities participated reflected the great awareness of the natural ventilation use, although there is not a clear criterion of the need of this ventilation for thermal comfort, as well as the need of a supportive use of air conditioning systems. Finally, the similarity of the climate conditions of the city analysed and the coastal cities from various countries in the south of Europe shows the possibility of using ventilation strategies as energy saving measures in other regions., Competing Interests: The authors declared that there is no conflict of interest., (© 2020 Elsevier Ltd. All rights reserved.)

Published
2020
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29. Glycyrrhetinic Acid-Functionalized Mesoporous Silica Nanoparticles for the Co-Delivery of DOX/CPT-PEG for Targeting HepG2 Cells.

Author

Martínez-Edo G, Fornaguera C, Borrós S, and Sánchez-García D

Abstract

A pH-triggered mesoporous silica nanoparticle (MSN)-based nano-vehicle for the dual delivery of doxorubicin (DOX)/camptothecin-PEG (CPT-PEG) has been prepared. To enhance its selectivity, the nanoparticles were decorated with glycyrrhetinic acid (GA) to target HepG2 cells. The highly insoluble CPT was derivatized with a reductive-cleavable PEG chain to improve its loading within the MSN. The preparation of these particles consisted of four steps. First, CPT-PEG was loaded within the pores of the MSN. Then, dihydrazide polyethylene glycol chains were introduced onto the surface of an aldehyde-functionalized MSN by means of a hydrazone bond. Afterwards, DOX was covalently attached to the other end of the dihydrazide polyethylene glycol chains. Finally, the resulting nanoparticles were decorated with GA by formation of an imine bond between the amino group of DOX and a benzaldehyde-GA derivative. The system was stable at physiological conditions and the release of both drugs was negligible. However, at acidic pH, a burst release of DOX and a gradual release of CPT-PEG takes place. GA-decorated drug delivery systems (DDS) selectively internalizes into HepG2. In vitro tests demonstrated that this system shows a great cytotoxicity towards HepG2 cells. Furthermore, glutathione cleavage of CPT prodrug assures the formation of free CPT leading to a synergistic effect in combination with DOX.

Published
2020
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30. Isothiocyanate-Functionalized Mesoporous Silica Nanoparticles as Building Blocks for the Design of Nanovehicles with Optimized Drug Release Profile.

Author

Martínez-Edo G, Llinàs MC, Borrós S, and Sánchez-García D

Abstract

A straightforward methodology for the synthesis of isothiocyanate-functionalized mesoporous silica nanoparticles (MSNs) by exposure of aminated MSNs to 1,1'-thiocarbonyldi-2(1 H )-pyridone is reported. These nanoparticles are chemically stable, water tolerant, and readily react with primary amines without the formation of any by-product. This feature allows the easy modification of the surface of the nanoparticles for tuning their physical properties and the introduction of gatekeepers on the pore outlets. As a proof-of-concept, amino-isothiocyanate-functionalized MSNs have been used for the design of a nanocontainer able to release the drug Ataluren. The release profile of the drug can be easily fine-tuned with the careful choice of the capping amine.

Published
2019
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31. Extended 2,2'-Bipyrroles: New Monomers for Conjugated Polymers with Tailored Processability.

Author

Texidó R, Anguera G, Colominas S, Borrós S, and Sánchez-García D

Abstract

The synthesis of 2,2'-bipyrroles substituted at positions 5,5' with pyrrolyl, N -methyl-pyrrolyl and thienyl groups and their application in the preparation of conducting polymers is reported herein. The preparation of these monomers consisted of two synthetic steps from a functionalized 2,2'-bipyrrole: Bromination of the corresponding 2,2'-bipyrrole followed by Suzuki or Stille couplings. These monomers display low oxidation potential compared to pyrrole because of the extended length of their conjugation pathway. The resulting monomers can be polymerized through oxidative/electropolymerization. Electrical conductivity and electrochromic properties of the electrodeposited polymeric films were evaluated using 4-point probe measurements and cyclic voltammetry to evaluate their applicability in electronics.

Published
2019
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32. Low diagnostic accuracy of fragile X tremor/ataxia syndrome diagnostic criteria in late onset ataxia.

Author

Dávila-Ortiz de Montellano DJ, Jara-Prado A, Rodríguez-Violante M, Camacho-Molina A, Carnevale A, Fresán-Orellana A, Camarena-Medellín B, Sánchez-García D, and Sotelo J

Subjects
Adult, Age of Onset, Ataxia genetics, Female, Fragile X Mental Retardation Protein genetics, Fragile X Syndrome genetics, Humans, Male, Sensitivity and Specificity, Tremor genetics, Ataxia diagnosis, Fragile X Syndrome diagnosis, Tremor diagnosis
Published
2019
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33. Preparation of a mesoporous silica-based nano-vehicle for dual DOX/CPT pH-triggered delivery.

Author

Llinàs MC, Martínez-Edo G, Cascante A, Porcar I, Borrós S, and Sánchez-García D

Subjects
Cell Line, Tumor, Drug Delivery Systems methods, Excipients chemistry, HeLa Cells, Humans, Hydrogen-Ion Concentration, Porosity, Camptothecin chemistry, Doxorubicin chemistry, Drug Carriers chemistry, Nanoparticles chemistry, Silicon Dioxide chemistry
Abstract

A dual doxorubicin/camptothecin (DOX/CPT) pH-triggered drug delivery mesoporous silica nanoparticle (MSN)-based nano-vehicle has been prepared. In this drug-delivery system (DDS), CPT is loaded inside the pores of the MSNs, while DOX is covalently attached to the surface of an aldehyde-functionalized MSN through a dihydrazide-polyethylene glycol chain. Thus, DOX and the linker act as pH-sensitive gatekeeper. The system is versatile and easy to assemble, not requiring the chemical modification of the drugs. While at physiological conditions the release of the drugs is negligible, at acidic pH a burst release of DOX and a gradual release of CPT take place. In vitro cytotoxicity tests have demonstrated that this DDS can deliver efficiently DOX and CPT for combination therapy.

Published
2018
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34. Functionalized 2,2'-Bipyrroles: Building Blocks for Pyrrolic Macrocycles.

Author

Anguera G, Brewster JT 2nd, Sánchez-García D, and Sessler JL

Abstract

Functionalized N-unsubstituted 2,2'-bipyrroles are basic building blocks for the preparation of pyrrolic macrocycles and natural products, such as prodigiosines. The aim of this review is to provide a description of the most important methodologies used to prepare 2,2'-bipyrroles and their central role as building blocks for the synthesis of porphyrinoids and property-defining structural elements therein.

Published
2018
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35. Stable 5,5'-Substituted 2,2'-Bipyrroles: Building Blocks for Macrocyclic and Materials Chemistry.

Author

Anguera G, Kauffmann B, Borrell JI, Borrós S, and Sánchez-García D

Abstract

The preparation and characterization of a family of stable 2,2'-bipyrroles substituted at positions 5 and 5' with thienyl, phenyl, TMS-ethynyl, and vinyl groups is reported herein. The synthesis of these new bipyrroles comprises three steps: formation of the corresponding 5,5'-unsubstituted bipyrrole, bromination, and Stille or Suzuki coupling. The best results in the coupling are obtained using the Stille reaction under microwave irradiation. The new compounds have been fully characterized by UV-vis absorption, fluorescence, and IR spectroscopies and cyclic voltammetry. X-ray single-crystal analysis of four of the synthesized bipyrroles indicates a trans coplanar geometry of the pyrrole rings. Furthermore, the substituents at positions 5,5' remain coplanar to the central rings. This particular geometry extends the π-conjugation of the systems, which is in agreement with a red-shifting observed for the λ max of the substituted molecules compared to the unsubstituted bipyrrole. All of these new compounds display a moderate fluorescence. In contrast with unsubstituted bipyrroles, these bipyrroles are endowed with a high chemical and thermal stability and solubility in organic solvents.

Published
2017
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36. Porphycenes and Related Isomers: Synthetic Aspects.

Author

Anguera G and Sánchez-García D

Subjects
Isomerism, Porphyrins chemistry
Abstract

Porphyrins, called the pigments of life, have been studied for decades. However, the first constitutional isomer of porphyrin, porphycene, was not synthesized until 1986. This milestone marked the beginning of a new era in the field of porphyrinoids and presented opportunities for the creation of an abundance of new pigments. The unique structural and electronic features of these compounds give rise to interesting physical and optical properties with applications in biomedicine and materials science. This review focuses on the synthetic methodologies available for the preparation of porphycenes (functionalized porphycenes, extended porphycenes, benzoporphycenes, naphthoporphycenes, and heteroanalogues) and the other known isomers, namely, corrphycene, hemiporphycene, and isoporphycene. Although the classical synthetic approaches are discussed, particular emphasis is placed on improvements to the known methodologies and recent advances in the field.

Published
2017
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37. Quaterpyrroles as building blocks for the synthesis of expanded porphyrins.

Author

Anguera G, Kauffmann B, Borrell JI, Borrós S, and Sánchez-García D

Subjects
Crystallography, X-Ray, Macrocyclic Compounds chemistry, Models, Molecular, Molecular Structure, Porphyrins chemistry, Pyrroles chemistry, Macrocyclic Compounds chemical synthesis, Porphyrins chemical synthesis, Pyrroles chemical synthesis
Abstract

A new family of quaterpyrroles and their application as building blocks for the synthesis of macrocycles is reported. The preparation of these quaterpyrroles consisted of two synthetic steps: bromination of 2,2'-bipyrroles bearing two electron-withdrawing groups followed by Suzuki coupling with 1-(tert-butoxycarbonyl)pyrrole-2-boronic acid. The resulting quaterpyrroles have been used to prepare an octaphyrin and a substituted cyclo[8]pyrrole. Additionally, the synthesis of a new macrocycle containing the quaterpyrrole and 2,5-di(1H-pyrrol-2-yl)thiophene moieties is presented.

Published
2015
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38. Application of stable isotopes (δ³⁴S-SO₄, δ¹⁸O-SO₄, δ¹⁵N-NO ₃, δ¹⁸O-NO ₃) to determine natural background and contamination sources in the Guadalhorce River Basin (southern Spain).

Author

Urresti-Estala B, Vadillo-Pérez I, Jiménez-Gavilán P, Soler A, Sánchez-García D, and Carrasco-Cantos F

Subjects
Agriculture, Isotopes analysis, Nitrogen Isotopes analysis, Spain, Sulfur Isotopes analysis, Environmental Monitoring methods, Rivers chemistry, Water Pollutants, Chemical analysis
Abstract

The integrated use of isotopes (δ(34)S-SO4, δ(18)O-SO4, δ(15)N-NO3, δ(18)O-NO3), taking into account existing hydrogeological knowledge of the study area (mainly hydrochemical), was applied in the Guadalhorce River Basin (southern Spain) to characterise SO4(2-) and NO3(-) sources, and to quantify natural background levels (NBLs) in groundwater bodies. According to Water Framework Directive 2000/60/EC and, more recently, Groundwater Directive 2006/118/EC, it is important to determine NBLs, as their correct assessment is the first, essential step to characterising groundwater bodies, establishing threshold values, assessing chemical status and identifying trends in pollutant concentrations. In many cases, NBLs are high for some parameters and types of groundwater, making it difficult to distinguish clearly between factors of natural or human origin. The main advantages of using stable isotopes in a complex area like the Guadalhorce River Basin that exhibits widely varying hydrogeological and hydrochemical conditions and longstanding anthropogenic influences (mainly agriculture, but also many others) is accurate determination of pollution sources and precise quantification of NBLs. Since chemical analyses only provides the concentration of pollutants in water and not the source, three isotopic sampling campaigns for sulphates (δ(34)S-SO4, δ(18)O-SO4) were carried out, in 2006, 2007 and 2012, and another one was conducted for nitrates (δ(15)N-NO3, δ(18)O-NO3), in 2009, in groundwater bodies in order to trace the origins of each pollutant. The present study identified different pollution sources of dissolved NO3(-) in groundwater using an isotopic composition and quantified the percentage of natural (lithology, chemical and biological processes) and anthropogenic (fertilisers, manure and sewage) SO4(2-) and matched a concentration associated with the percentage in order to determine the NBLs in the basin., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Published
2015
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39. Modifications of microvascular EC surface modulate phototoxicity of a porphycene anti-ICAM-1 immunoconjugate; therapeutic implications.

Author

Rosàs E, Santomá P, Duran-Frigola M, Hernandez B, Llinàs MC, Ruiz-González R, Nonell S, Sánchez-García D, Edelman ER, and Balcells M

Subjects
Cells, Cultured, Endothelial Cells immunology, Humans, Microvessels cytology, Photosensitizing Agents chemical synthesis, Photosensitizing Agents chemistry, Surface Properties, Endothelial Cells drug effects, Immunoconjugates immunology, Immunotherapy, Intercellular Adhesion Molecule-1 immunology, Photosensitizing Agents pharmacology, Porphyrins pharmacology
Abstract

Inflammation and shear stress can upregulate expression of cellular adhesion molecules in endothelial cells (EC). The modified EC surface becomes a mediating interface between the circulating blood elements and the endothelium, and grants opportunity for immunotherapy. In photodynamic therapy (PDT), immunotargeting might overcome the lack of selectivity of currently used sensitizers. In this study, we hypothesized that differential ICAM-1 expression modulates the effects of a drug targeted to surface ICAM-1. A novel porphycene-anti-ICAM-1 conjugate was synthesized and applied to treat endothelial cells from macro and microvasculature. Results show that the conjugate induces phototoxicity in inflamed, but not in healthy, microvascular EC. Conversely, macrovascular EC exhibited phototoxicity regardless of their state. These findings have two major implications; the relevance of ICAM-1 as a modulator of drug effects in microvasculature, and the potential of the porphycene bioconjugate as a promising novel PDT agent.

Published
2013
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40. Efficient induction of apoptosis in HeLa cells by a novel cationic porphycene photosensitizer.

Author

Ruiz-González R, Acedo P, Sánchez-García D, Nonell S, Cañete M, Stockert JC, and Villanueva A

Subjects
Cations chemistry, Cell Survival drug effects, Cell Survival radiation effects, Dose-Response Relationship, Drug, Dose-Response Relationship, Radiation, Flow Cytometry, HeLa Cells, Humans, Light, Microscopy, Fluorescence, Molecular Structure, Photochemotherapy methods, Photosensitizing Agents chemistry, Porphyrins chemistry, Apoptosis drug effects, Apoptosis radiation effects, Photosensitizing Agents pharmacology, Porphyrins pharmacology
Abstract

In the present study we analyze the photobiological properties of 2,7,12-tris(α-pyridinio-p-tolyl)-17-(p-(methoxymethyl)phenyl) porphycene (Py3MeO-TBPo) in Hela cells, in order to assess its potential as a new photosensitizer for photodynamic therapy of cultured tumor cells. Using 0.5 μM Py3MeO-TBPo, flow cytometry studies demonstrated an increase of intracellular drug levels related to the incubation time, reaching a maximum at 18 h. LysoTracker(®) Green (LTG) and MitoTracker(®) Green (MTG) probes were used to identify the subcellular localization. Upon exposure to ultraviolet excitation, red porphycene fluorescence was detected as red granules in the cytoplasm that colocalized with LTG. No significant toxic effects were detected for Py3MeO-TBPo in the dark at concentrations below 1 μM. In contrast, Py3MeO-TBPo combined with red-light irradiation induced concentration- and fluence-dependent HeLa cells inactivation. Besides, all photodynamic protocols assayed induced a clear effect of cell detachment inhibition after trypsin treatment. Both apoptotic and necrotic cell death mechanisms can occur in HeLa cells depending on the experimental protocol. After 18 h incubation with 0.5 μM Py3MeO-TBPo and subsequent red light irradiation (3.6 J/cm(2)), a high number of cells die by apoptosis, as evaluated by morphological alterations, immunofluorescent relocalization of Bax from cytosol to mitochondria, and TUNEL assay. Likewise, immunofluorescence techniques showed that cytochrome c is released from mitochondria into cytosol in cells undergoing apoptosis, which occurs immediately after relocation of Bax in mitochondria. The highest amount of apoptosis appeared 24 h after treatment (70%) and this cell death occurred without cell detachment to the substrate. In contrast, with 0.75 μM Py3MeO-TBPo and 3.6 J/cm(2) irradiation, morphological changes showed a preferential necrotic cell death. Singlet oxygen was identified as the cytotoxic agent involved in cell photoinactivation. Moreover, cell cultures pre-exposed to the singlet oxygen scavenger sodium azide showed pronounced protection against the loss of viability induced by Py3MeO-TBPo and light. Different changes in distribution and organization of cytoskeletal elements (microtubules and actin microfilaments) as well as the protein vinculin, after apoptotic and necrotic photodynamic treatments have been analyzed. Neither of these two cell death mechanisms (apoptosis or necrosis) induced cell detachment. In summary, Py3MeO-TBPo appears to meet the requirements for further scrutiny as a very good photosensitizer for photodynamic therapy: it is water soluble, has a high absorption in the red spectral region (where light penetration in tissue is higher), and is able to induce effective high apoptotic rate (70%) related to the more widely studied photosensitizers., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Published
2013
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41. Synthesis, characterization, and photoinduced antibacterial activity of porphyrin-type photosensitizers conjugated to the antimicrobial peptide apidaecin 1b.

Author

Dosselli R, Tampieri C, Ruiz-González R, De Munari S, Ragàs X, Sánchez-García D, Agut M, Nonell S, Reddi E, and Gobbo M

Subjects
Anti-Bacterial Agents chemistry, Chromatography, High Pressure Liquid, Gram-Negative Bacteria drug effects, Mass Spectrometry, Microbial Sensitivity Tests, Photochemical Processes, Photosensitizing Agents chemistry, Porphyrins chemical synthesis, Porphyrins chemistry, Porphyrins pharmacology, Singlet Oxygen metabolism, Spectrometry, Fluorescence, Spectrophotometry, Ultraviolet, Anti-Bacterial Agents chemical synthesis, Anti-Bacterial Agents pharmacology, Antimicrobial Cationic Peptides chemistry, Photosensitizing Agents chemical synthesis, Photosensitizing Agents pharmacology
Abstract

Antimicrobial photodynamic therapy (aPDT) is an emerging treatment for bacterial infections that is becoming increasingly more attractive because of its effectiveness against multi-antibiotic-resistant strains and unlikelihood of inducing bacterial resistance. Among the strategies to enhance the efficacy of PDT against Gram-negative bacteria, the binding to a cationic antimicrobial peptide offers the attractive prospect for improving both the water solubilty and the localization of the photoactive drug in bacteria. In this work we have compared a number of free and apidaecin-conjugated photosensitizers (PSs) differing in structure and charge. Our results indicate that the conjugation of per se ineffective highly hydrophobic PSs to a cationic peptide produces a photosensitizing agent effective against Gram-negative bacteria. Apidaecin cannot improve the phototoxic activity of cationic PSs, which mainly depends on a very high yield of singlet oxygen production in the surroundings of the bacterial outer membrane. Apidaecin-PS conjugates appear most promising for treatment protocols requiring repeated washing after sensitizer delivery.

Published
2013
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42. Synthesis of 2-arylamino substituted 5,6-dihydropyrido[2,3-d]pyrimidine-7(8H)-ones from arylguanidines.

Author

Galve I, Puig de la Bellacasa R, Sánchez-García D, Batllori X, Teixidó J, and Borrell JI

Subjects
Dioxanes chemistry, Transition Temperature, Guanidines chemistry, Nitriles chemical synthesis, Pyrimidines chemical synthesis, Pyrimidinones chemistry
Abstract

A practical protocol was developed for the synthesis of 2-arylamino substituted 4-amino-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-ones from α,β-unsaturated esters, malononitrile, and an aryl substituted guanidine via the corresponding 3-aryl-3,4,5,6- tetrahydropyrido[2,3-d]pyrimidin-7(8H)-ones. Such compounds are formed upon treatment of 2-methoxy-6-oxo-1,4,5,6-tetrahydropyridine-3-carbonitriles with an aryl substituted guanidine in 1,4-dioxane and are converted to the desired 4-aminopyridopyrimidines with NaOMe/MeOH through a Dimroth rearrangement. The overall yields of this three-step protocol are, generally speaking, higher than the multicomponent reaction, previously developed by our group, between an α,β-unsaturated ester, malononitrile, and an aryl substituted guanidine.

Published
2012
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43. Tautomerization in 2,7,12,17-tetraphenylporphycene and 9-amino-2,7,12,17-tetraphenylporphycene: influence of asymmetry on the direction of the transition moment.

Author

Fita P, Pszona M, Orzanowska G, Sánchez-García D, Nonell S, Vauthey E, and Waluk J

Abstract

Femtosecond transient absorption anisotropy studies have been performed for two porphycenes of different symmetry. In 2,7,12,17-tetraphenylporphycene, the chemical identity of two trans forms implies a change in the S(0)-S(1) transition-moment direction upon tautomerization. Exploiting this phenomenon, the rates of double hydrogen transfer in both the S(0) and S(1) states (1.4×10(12)  s(-1) and 2.7×10(11)  s(-1) , respectively) have been determined by performing time-resolved anisotropy studies. In the asymmetric 9-amino-2,7,12,17-tetraphenylporphycene, tautomerization occurs with a similar rate in the ground state. In the S(1) state, the reaction is hindered in its vibrationally relaxed form, but the excitation spectra suggest that it may occur for an unrelaxed molecule. Unlike all porphycenes that have been studied so far, 9-amino-2,7,12,17-tetraphenylporphycene does not reveal significant changes in anisotropy owing to intramolecular double hydrogen transfer; rather, the transition-moment directions are similar in the two tautomeric forms. Analysis of the molecular orbitals allows for an explanation of the "locking" of the transition moments: it is due to a large splitting of the two HOMO orbitals, which retain the order of their energies in the two tautomers., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2012
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44. Dual fluorescence in 9-amino-2,7,12,17-tetraphenylporphycene.

Author

Duran-Frigola M, Tejedor-Estrada R, Sánchez-García D, and Nonell S

Abstract

The absorption spectrum of the asymmetric 9-amino-2,7,12,17-tetraphenylporphycene shows new, strongly red-shifted bands compared to the symmetric parental 2,7,12,17-tetraphenylporphycene and to the also asymmetric 9-acetoxy-2,7,12,17-tetraphenylporphycene. Dual emission is also observed with relative contributions that depend strongly on the excitation wavelength and temperature. The gap between the two fluorescence bands is 84 nm. Tautomerization in both the ground and excited states is shown to account for these observations, the 9-amino group being particularly able to selectively lower the energy of the first excited singlet state of just one of the trans tautomers. Introduction of amino groups in porphycenes may be a convenient way to gain a deeper insight into the tautomerization mechanisms in this macrocyclic core.

Published
2011
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45. Cationic porphycenes as potential photosensitizers for antimicrobial photodynamic therapy.

Author

Ragàs X, Sánchez-García D, Ruiz-González R, Dai T, Agut M, Hamblin MR, and Nonell S

Subjects
Animals, Burns drug therapy, Burns microbiology, Candida drug effects, Cations, Gram-Negative Bacteria drug effects, Gram-Positive Bacteria drug effects, Male, Methicillin-Resistant Staphylococcus aureus, Mice, Mice, Inbred BALB C, Photosensitizing Agents chemistry, Photosensitizing Agents pharmacology, Porphyrins chemistry, Porphyrins pharmacology, Solubility, Staphylococcal Infections drug therapy, Staphylococcal Infections microbiology, Structure-Activity Relationship, Bacterial Infections drug therapy, Photochemotherapy, Photosensitizing Agents chemical synthesis, Porphyrins chemical synthesis
Abstract

Structures of typical photosensitizers used in antimicrobial photodynamic therapy are based on porphyrins, phthalocyanines, and phenothiazinium salts, with cationic charges at physiological pH values. However, derivatives of the porphycene macrocycle (a structural isomer of porphyrin) have barely been investigated as antimicrobial agents. Therefore, we report the synthesis of the first tricationic water-soluble porphycene and its basic photochemical properties. We successfully tested it for in vitro photoinactivation of different Gram-positive and Gram-negative bacteria, as well as a fungal species (Candida) in a drug-dose and light-dose dependent manner. We also used the cationic porphycene in vivo to treat an infection model comprising mouse third degree burns infected with a bioluminescent methicillin-resistant Staphylococcus aureus strain. There was a 2.6-log(10) reduction (p < 0.001) of the bacterial bioluminescence for the PDT-treated group after irradiation with 180 J·cm(-2) of red light.

Published
2010
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46. Nanosized hybrid oligoamide foldamers: aromatic templates for the folding of multiple aliphatic units.

Author

Sánchez-García D, Kauffmann B, Kawanami T, Ihara H, Takafuji M, Delville MH, and Huc I

Subjects
Carboxylic Acids chemistry, Crystallography, X-Ray, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Conformation, Pyridines chemistry, Quinolines chemistry, Amides chemistry, Nanoparticles chemistry
Abstract

Oligoamide sequences comprised of both 8-amino-2-quinolinecarboxylic acid "Q" and 6-aminomethyl-2-pyridinecarboxylic acid "P" have been synthesized. It was found that the aliphatic amine of P greatly facilitates amide couplings, as opposed to the aromatic amine of Q, which enabled us to prepare sequences having up to 40 units. The conformation and conformational stability of these oligomers were characterized in the solid state using X-ray crystallography and in solution using NMR and various chromatographic techniques. Q(n) oligomers adopt very stable helically folded conformations whereas P(n) oligomers do not fold and impart conformational preferences distinct from those of Q units. When a P(n) segments is attached at the end of a Q(4) segment, a couple P units appear to follow the folding pattern imposed by the Q(n) segment, but P units remote from the Q(n) segment do not fold. When a P(n) segment is inserted between two Q(4) segments, the P(n) segment adopts the canonical helical conformation imposed by the Q units at least up to two full helical turns (n = 5). However, the overall stability of the helix tends to decrease as the number of P units increases. When noncontiguous P units separated by Q(4) segments are incorporated in a sequence, they all adopt the helical conformation imposed by Q monomers and the overall helix stability increases when helix length increases. For example, a 40mer with a sequence (PQ(4))(8) folds into a rod-like helix spanning over 16 turns with a length of 5.6 nm. This investigation thus demonstrates that remarkably long (nanometers) yet well-defined foldamers can be efficiently synthesized stepwise and that their helical stability may be continuously tuned upon controlling the ratio and sequence of P and Q monomers.

Published
2009
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47. Singlet oxygen photosensitisation by the fluorescent probe Singlet Oxygen Sensor Green.

Author

Ragàs X, Jiménez-Banzo A, Sánchez-García D, Batllori X, and Nonell S

Subjects
Light, Methanol chemistry, Singlet Oxygen chemistry, Ultraviolet Rays, Fluorescent Dyes chemistry, Fluorescent Dyes radiation effects, Methanol radiation effects, Photosensitizing Agents chemistry, Photosensitizing Agents radiation effects, Singlet Oxygen analysis
Abstract

The fluorescent probe Singlet Oxygen Sensor Green is able to produce singlet oxygen under exposure to UV or visible radiation.

Published
2009
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48. A bisfullerene-bis(dipyrrinato)zinc complex: electronic coupling and charge separation in an easy-to-assemble synthetic system.

Author

Rio Y, Sánchez-García D, Seitz W, Torres T, Sessler JL, and Guldi DM

Subjects
Electrochemistry, Molecular Structure, Fullerenes chemistry, Metalloporphyrins chemical synthesis, Metalloporphyrins chemistry, Zinc chemistry
Abstract

Getting connected: The use of a bis(dipyrrinato)zinc(II)) linker allows the facile tethering of two C(60) subunits and gives rise to an electronically coupled system that allows effective charge separation following photoexcitation (see figure).

Published
2009
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49. One-pot synthesis of substituted 2,2'-bipyrroles. A straightforward route to aryl porphycenes.

Author

Sánchez-García D, Borrell JI, and Nonell S

Subjects
Crystallography, X-Ray, Models, Molecular, Molecular Structure, Porphyrins chemistry, Stereoisomerism, Porphyrins chemical synthesis, Pyrroles chemical synthesis, Pyrroles chemistry
Abstract

A one-pot reaction for the synthesis of 4,4'-diaryl- and 4,4'-diheteroaryl-substituted 2,2'-bipyrroles is described. The new methodology is based on the oxidative coupling of a 2-trimethylstannylated pyrrole and does not require chromatography. These 2,2'-bipyrroles can be used as precursors in a expeditious synthesis of 2,7,12,17-tetraaryl-porphycenes.

Published
2009
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