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1. Proteome Dynamics of Persulfidation in Leaf Tissue under Light/Dark Conditions and Carbon Deprivation

Author

Ana Jurado-Flores, Cecilia Gotor, and Luis C. Romero

Subjects
carbon starvation, light photoperiod, persulfidation, quantitative proteomics, sulfur assimilation, Therapeutics. Pharmacology, RM1-950
Abstract

Hydrogen sulfide (H2S) acts as a signaling molecule in plants, bacteria, and mammals, regulating various physiological and pathological processes. The molecular mechanism by which hydrogen sulfide exerts its action involves the posttranslational modification of cysteine residues to form a persulfidated thiol motif. This research aimed to study the regulation of protein persulfidation. We used a label-free quantitative approach to measure the protein persulfidation profile in leaves under different growth conditions such as light regimen and carbon deprivation. The proteomic analysis identified a total of 4599 differentially persulfidated proteins, of which 1115 were differentially persulfidated between light and dark conditions. The 544 proteins that were more persulfidated in the dark were analyzed, and showed significant enrichment in functions and pathways related to protein folding and processing in the endoplasmic reticulum. Under light conditions, the persulfidation profile changed, and the number of differentially persulfidated proteins increased up to 913, with the proteasome and ubiquitin-dependent and ubiquitin-independent catabolic processes being the most-affected biological processes. Under carbon starvation conditions, a cluster of 1405 proteins was affected by a reduction in their persulfidation, being involved in metabolic processes that provide primary metabolites to essential energy pathways and including enzymes involved in sulfur assimilation and sulfide production.

Published
2023
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2. Label-Free Quantitative Proteomic Analysis of Nitrogen Starvation in Arabidopsis Root Reveals New Aspects of H2S Signaling by Protein Persulfidation

Author

Ana Jurado-Flores, Luis C. Romero, and Cecilia Gotor

Subjects
Arabidopsis, autophagy, cysteine, hydrogen sulfide, persulfidation, proteomic, Therapeutics. Pharmacology, RM1-950
Abstract

Hydrogen sulfide (H2S)-mediated signaling pathways regulate many physiological and pathophysiological processes in mammalian and plant systems. The molecular mechanism by which hydrogen sulfide exerts its action involves the posttranslational modification of cysteine residues to form a persulfidated thiol motif. We developed a comparative and label-free quantitative proteomic analysis approach for the detection of endogenous persulfidated proteins in N-starved Arabidopsis thaliana roots by using the tag-switch method. In this work, we identified 5214 unique proteins from root tissue that were persulfidated, 1674 of which were quantitatively analyzed and found to show altered persulfidation levels in vivo under N deprivation. These proteins represented almost 13% of the entire annotated proteome in Arabidopsis. Bioinformatic analysis revealed that persulfidated proteins were involved in a wide range of biological functions, regulating important processes such as primary metabolism, plant responses to stresses, growth and development, RNA translation and protein degradation. Quantitative mass spectrometry analysis allowed us to obtain a comprehensive view of hydrogen sulfide signaling via changes in the persulfidation levels of key protein targets involved in ubiquitin-dependent protein degradation and autophagy, among others.

Published
2021
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3. Exploring the Functional Relationship between y-Type Thioredoxins and 2-Cys Peroxiredoxins in Arabidopsis Chloroplasts

Author

Ana Jurado-Flores, Víctor Delgado-Requerey, Alicia Gálvez-Ramírez, Leonor Puerto-Galán, Juan Manuel Pérez-Ruiz, and Francisco Javier Cejudo

Subjects
2-Cys peroxiredoxin, thioredoxin y, NTRC, thioredoxin x, redox regulation, stress response, Therapeutics. Pharmacology, RM1-950
Abstract

Thioredoxins (Trxs) are small, ubiquitous enzymes that catalyze disulphide–dithiol interchange in target enzymes. The large set of chloroplast Trxs, including f, m, x and y subtypes, use reducing equivalents fueled by photoreduced ferredoxin (Fdx) for fine-tuning photosynthetic performance and metabolism through the control of the activity of redox-sensitive proteins. Although biochemical analyses suggested functional diversity of chloroplast Trxs, genetic studies have established that deficiency in a particular Trx subtype has subtle phenotypic effects, leading to the proposal that the Trx isoforms are functionally redundant. In addition, chloroplasts contain an NADPH-dependent Trx reductase with a joint Trx domain, termed NTRC. Interestingly, Arabidopsis mutants combining the deficiencies of x- or f-type Trxs and NTRC display very severe growth inhibition phenotypes, which are partially rescued by decreased levels of 2-Cys peroxiredoxins (Prxs). These findings indicate that the reducing capacity of Trxs f and x is modulated by the redox balance of 2-Cys Prxs, which is controlled by NTRC. In this study, we explored whether NTRC acts as a master regulator of the pool of chloroplast Trxs by analyzing its functional relationship with Trxs y. While Trx y interacts with 2-Cys Prxs in vitro and in planta, the analysis of Arabidopsis mutants devoid of NTRC and Trxs y suggests that Trxs y have only a minor effect, if any, on the redox state of 2-Cys Prxs.

Published
2020
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4. Optimal doses of caspofungin during continuous venovenous hemodiafiltration in critically ill patients

Author

Gerardo Aguilar, Rafael Ferriols, Angels Lozano, Carlos Ezquer, José A. Carbonell, Ana Jurado, Juan Carrizo, Ferran Serralta, Jaume Puig, David Navarro, Manuel Alos, and F. Javier Belda

Subjects
Echinocandins, Continuous renal replacement therapy, Invasive candidiasis, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Published
2017
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5. Sulfide promotes tolerance to drought through protein persulfidation in Arabidopsis

Author

Ana Jurado-Flores, Angeles Aroca, Luis C Romero, and Cecilia Gotor

Subjects
Physiology, Plant Science
Abstract

Hydrogen sulfide (H2S) is a signaling molecule that regulates essential plant processes. In this study, the role of H2S during drought was analysed, focusing on the underlying mechanism. Pretreatments with H2S before imposing drought on plants substantially improved the characteristic stressed phenotypes under drought and decreased the levels of typical biochemical stress markers such as anthocyanin, proline, and hydrogen peroxide. H2S also regulated drought-responsive genes and amino acid metabolism, and repressed drought-induced bulk autophagy and protein ubiquitination, demonstrating the protective effects of H2S pretreatment. Quantitative proteomic analysis identified 887 significantly different persulfidated proteins between control and drought stress plants. Bioinformatic analyses of the proteins more persulfidated in drought revealed that the most enriched biological processes were cellular response to oxidative stress and hydrogen peroxide catabolism. Protein degradation, abiotic stress responses, and the phenylpropanoid pathway were also highlighted, suggesting the importance of persulfidation in coping with drought-induced stress. Our findings emphasize the role of H2S as a promoter of enhanced tolerance to drought, enabling plants to respond more rapidly and efficiently. Furthermore, the main role of protein persulfidation in alleviating reactive oxygen species accumulation and balancing redox homeostasis under drought stress is highlighted.

Published
2023
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7. Intraoperative positive end-expiratory pressure and postoperative pulmonary complications: a patient-level meta-analysis of three randomised clinical trials

Author

Niklas S. Campos, Thomas Bluth, Sabrine N.T. Hemmes, Julian Librero, Natividad Pozo, Carlos Ferrando, Lorenzo Ball, Guido Mazzinari, Paolo Pelosi, Marcelo Gama de Abreu, Marcus J. Schultz, A. Serpa Neto, Sabrine NT. Hemmes, Paolo Severgnini, Markus W. Hollmann, Jan M. Binnekade, Hermann Wrigge, Jaume Canet, Michael Hiesmayr, Werner Schmid, Edda Tschernko, Samir Jaber, Göran Hedenstierna, Christian Putensen, Agnes Marti, Alessandro Bacuzzi, Alexander Brodhun, Alexandre Molin, Alfred Merten, Ana Parera, Andrea Brunelli, Andrea Cortegiani, Andreas Güldner, Andreas W. Reske, Angelo Gratarola, Antonino Giarratano, Bea Bastin, Bjorn Heyse, Branka Mazul-Sunko, Bruno Amantea, Bruno Barberis, Christopher Uhlig, Conrado Minguez Marín, Cristian Celentano, Daniela La Bella, David D’Antini, David Velghe, Demet Sulemanji, Edoardo De Robertis, Eric Hartmann, Francesca Montalto, Francesco Tropea, Gary H. Mills, Gilda Cinnella, Giorgio Della Rocca, Girolamo Caggianelli, Giulia Pellerano, Giuseppina Mollica, Guillermo Bugedo, Jan-Paul Mulier, Jeroen Vandenbrande, Johann Geib, Jonathan Yaqub, Jorge Florez, Juan F. Mayoral, Juraj Sprung, Jurgen Van Limmen, Lieuwe DJ. Bos, Luc de Baerdemaeker, Luc Jamaer, Luigi Spagnolo, Lydia Strys, Manuel Granell Gil, Marcos F. Vidal Melo, Maria Carmen Unzueta, Maria Victoria Moral, Marion Ferner, Martin Weiss, Massimo Vanoni, Maximilian S. Schaefer, Mercè Prieto, Michele Grio, Peter Markus Spieth, Philipp Simon, Phoebe Bodger, Pilar Sierra, Rita Laufenberg-Feldmann, Roberta Rusca, Rodolfo Proietti, Santi Maurizio Raineri, Santo Caroleo, Sergi Sabaté, Stefan De Hert, Stefano Pezzato, Tanja A. Treschan, Tatjana Goranovic, Thea Koch, Thomas Kiss, Valter Perilli, Virginia Cegarra, Javier Belda, Marina Soro, Carmen Unzueta, Fernando Suarez-Sipmann, Julián Librero, Alicia Llombart, Lucas Rovira, Manuel Granell, César Aldecoa, Oscar Diaz-Cambronero, Jaume Balust, Ignacio Garutti, Rafael Gonzalez, Lucia Gallego, Santiago Garcia del Valle, Javier Redondo, David Pestaña, Aurelio Rodríguez, Javier García, Manuel de la Matta, Maite Ibáñez, Francisco Barrios, Samuel Hernández, Vicente Torres, Salvador Peiró, Abigail Villena, Albert Carramiñana, Alberto Gallego-Casilda, Alejandro Duca, Amalia Alcón, Amanda Miñana, Ana Asensio, Ana Colás, Ana Isabel Galve, Ana Izquierdo, Ana Jurado, Ana María Pérez, Ana Mugarra, Andrea Gutierrez, Ángeles De Miguel, Angels Lozano, Antonio Katime, Antonio Romero, Beatriz Garrigues, Begoña Ayas, Blanca Arocas, Carlos Delgado, Carmen Fernández, Carolina Romero, Clara Gallego, Cristina Garcés, Cristina Lisbona, Cristina Parrilla, Daniel López-Herrera, Domingo González, Eduardo Llamazares, Elena Del Rio, Elena Lozano, Ernesto Pastor, Estefanía Chamorro, Estefanía Gracia, Ester Sánchez, Esther Romero, Fernando Díez, Ferran Serralta, Francisco Daviu, Francisco Sandín, Gerardo Aguilar, Gerardo Tusman, Gonzalo Azparren, Graciela Martínez-Pallí, Inmaculada Benítez, Inmaculada Hernandéz, Inmaculada India, Irene León, Isabel Fuentes, Isabel Ruiz, Jaume Puig, Javie Ignacio Román, Jesús Acosta, Jesús Rico-Feijoo, Jonathan Olmedo, Jose A. Carbonell, Jose M. Alonso, Jose María Pérez, Jose Miguel Marcos, Jose Navarro, Jose Valdivia, Juan Carrizo, Laura Piqueras, Laura Soriano, Laura Vaquero, Lisset Miguel, Lorena Muñoz, Lucia Valencia, Luis Olmedilla, Mᵃ Justina Etulain, Manuel Tisner, María Barrio, María Dolores Alonso, María García, María J. Hernández, María José Alberola, María Parra, María Pilar Argente, María Vila, Mario De Fez, Marta Agilaga, Marta Gine, Mercedes Ayuso, Mercedes García, Natalia Bejarano, Natalia Peña, Nazario Ojeda, Nilda Martínez, Nuria García, Oto Padrón, Pablo García, Paola Valls, Patricia Cruz, Patricia Piñeiro, Pedro Charco, Rafael Anaya, Ramiro López, Rayco Rodríguez, Rocío Martínez, Roger Pujol, Rosa Dosdá, Rosa Lardies, Ruben Díaz, Rubén Villazala, Sara Zapatero, Sergio Cabrera, Sergio Sánchez, Silvia Martin, Suzana Diaz, Tania Franco, Tania Moreno, Tania Socorro, Vicente Gilabert, Victor Balandrón, Victoria Moral, Virgina Cegarra, Viviana Varón, Fernando Abelha, Sühayla Abitağaoğlu, Marc Achilles, Afeez Adebesin, Ine Adriaensens, Charles Ahene, Fatima Akbar, Mohammed Al Harbi, Rita Al Khoury al Kallab, Xavier Albanel, Florence Aldenkortt, Rawan Abdullah Saleh Alfouzan, Reef Alruqaie, Fernando Altermatt, Bruno Luís de Castro Araujo, Genaro Arbesú, Hanna Artsi, Caterina Aurilio, Omer Hilmi Ayanoglu, Harris Baig, Yolanda Baird, Konstantin Balonov, Samantha Banks, Xiaodong Bao, Mélanie Baumgartner, Isabel Belda Tortosa, Alice Bergamaschi, Lars Bergmann, Luca Bigatello, Elena Biosca Pérez, Katja Birr, Elird Bojaxhi, Chiara Bonenti, Iwona Bonney, Elke M.E. Bos, Sara Bowman, Leandro Gobbo Braz, Elisa Brugnoni, Sorin J. Brull, Iole Brunetti, Andrea Bruni, Shonie L. Buenvenida, Cornelius Johannes Busch, Giovanni Camerini, Beatrice Capatti, Javiera Carmona, Jaime Carungcong, Marta Carvalho, Anat Cattan, Carla Cavaleiro, Davide Chiumello, Stefano Ciardo, Mark Coburn, Umberto Colella, Victor Contreras, Pelin Corman Dincer, Elizabeth Cotter, Marcia Crovetto, William Darrah, Simon Davies, Enrique Del Cojo Peces, Ellise Delphin, John Diaper, Paulo do Nascimento Junior, Valerio Donatiello, Jing Dong, Maria do Socorro Dourado, Alexander Dullenkopf, Felix Ebner, Hamed Elgendy, Christoph Ellenberger, Dilek Erdoğan Arı, Thomas Ermert, Fadi Farah, Ana Fernandez-Bustamante, Cristina Ferreira, Marco Fiore, Ana Fonte, Christina Fortià Palahí, Andrea Galimberti, Najia Garofano, Luca Gregorio Giaccari, Fernando Gilsanz, Felix Girrbach, Luca Gobbi, Marc Bernard Godfried, Nicolai Goettel, Peter A. Goldstein, Or Goren, Andrew Gorlin, Juan Graterol, Pierre Guyon, Kevin Haire, Philippe Harou, Antonia Helf, Gunther Hempel, María José Hernández Cádiz, Björn Heyse, Ivan Huercio, Jasmina Ilievska, Lien Jakus, Vijay Jeganath, Yvonne Jelting, Minoa Jung, Barbara Kabon, Aalok Kacha, Maja Karaman Ilić, Arunthevaraja Karuppiah, Ayse Duygu Kavas, Gleicy Keli Barcelos, Todd A. Kellogg, Johann Kemper, Romain Kerbrat, Suraya Khodr, Peter Kienbaum, Bunyamin Kir, Selin Kivrak, Vlasta Klarić, Ceren Köksal, Ana Kowark, Peter Kranke, Bahar Kuvaki, Biljana Kuzmanovska, John Laffey, Mirko Lange, Marília Freitas de Lemos, Marc-Joseph Licker, Manuel López-Baamonde, Antonio López-Hernández, Mercedes Lopez-Martinez, Stéphane Luise, Mark MacGregor, Danielle Magalhães, Julien Maillard, Patrizia Malerbi, Natesan Manimekalai, Michael Margarson, Klaus Markstaller, Archer K. Martin, David P. Martin, Yvette N. Martin, Julia Martínez-Ocon, Ignacio Martin-Loeches, Emilio Maseda, Idit Matot, Niamh McAuliffe, Travis J. McKenzie, Paulina Medina, Melanie Meersch, Angelika Menzen, Els Mertens, Bernd Meurer, Tanja Meyer-Treschan, Changhong Miao, Camilla Micalizzi, Morena Milić, Norma Sueli Pinheiro Módolo, Pierre Moine, Patrick Mölders, Ana Montero-Feijoo, Enrique Moret, Markus K. Muller, Zoe Murphy, Pramod Nalwaya, Filip Naumovski, Paolo Navalesi, Lais Helena Navarro e Lima, Višnja Nesek Adam, Claudia Neumann, Christopher Newell, Zoulfira Nisnevitch, Junaid Nizamuddin, Cecilia Novazzi, Michael O'Connor, Günther Oprea, Mukadder Orhan Sungur, Şule Özbilgin, Maria Caterina Pace, Marcos Pacheco, Balaji Packianathaswamy, Estefania Palma Gonzalez, Fotios Papaspyros, Sebastián Paredes, Maria Beatrice Passavanti, Juan Cristobal Pedemonte, Sanja Peremin, Christoph Philipsenburg, Daniela Pinho, Silvia Pinho, Linda M. Posthuma, Vincenzo Pota, Benedikt Preckel, Paolo Priani, Mohamed Aymen Rached, Aleksandar Radoeshki, Riccardo Ragazzi, Tamilselvan Rajamanickam, Arthi Rajamohan, Harish Ramakrishna, Desikan Rangarajan, Christian Reiterer, J. Ross Renew, Thomas Reynaud, Rhidian Rhys, Eva Rivas, Luisa Robitzky, Rolf Rossaint, Francesca Rubulotta, Humberto S. Machado, Catarina S. Nunes, Giovanni Sabbatini, Jon D. Samuels, Josep Martí Sanahuja, Pasquale Sansone, Alice Santos, Mohamed Sayedalahl, Martin Scharffenberg, Eduardo Schiffer, Nadja Schliewe, Raoul Schorer, Roman Schumann, Gabriele Selmo, Mar Sendra, Mert Senturk, Kate Shaw, Mirjana Shosholcheva, Abdulrazak Sibai, Francesca Simonassi, Claudia Sinno, Nukhet Sivrikoz, Vasiliki Skandalou, Neil Smith, Maria Soares, Tania Socorro Artiles, Diogo Sousa Castro, Miguel Sousa, Savino Spadaro, Emmanouil Stamatakis, Luzius A. Steiner, Andrea Stevenazzi, Alejandro Suarez-de-la-Rica, Mélanie Suppan, Robert Teichmann, José Maria Tena Guerrero, Bram Thiel, Raquel Tolós, Gulbin Tore Altun, Michelle Tucci, Zachary A. Turnbull, Žana Turudić, Matthias Unterberg, Yves Van Nieuwenhove, Julia Van Waesberghe, Marcos Francisco Vidal Melo, Bibiana Vitković, Luigi Vivona, Marcela Vizcaychipi, Carlo Alberto Volta, Anne Weber, Toby N. Weingarten, Jakob Wittenstein, Piet Wyffels, Julio Yagüe, David Yates, Ayşen Yavru, Lilach Zac, Jing Zhong, Anesthesiology, Intensive Care Medicine, ACS - Pulmonary hypertension & thrombosis, ACS - Diabetes & metabolism, ACS - Microcirculation, Campos, Niklas S, Bluth, Thoma, Hemmes, Sabrine N T, Librero, Julian, Pozo, Natividad, Ferrando, Carlo, Ball, Lorenzo, Mazzinari, Guido, Pelosi, Paolo, Gama de Abreu, Marcelo, Schultz, Marcus J, Serpa Neto, A, investigators for the PROVHILO study including, Cortegiani, Andrea, Raineri, Santi Maurizio, and Giarratano, Antonino

Subjects
Adult, Lung Diseases, PEEP, postoperative pulmonary complications, mechanical ventilation, Positive-Pressure Respiration, surgery, Anesthesiology and Pain Medicine, Postoperative Complications, Tidal Volume, Humans, Postoperative Period, Lung, Randomized Controlled Trials as Topic
Abstract

BACKGROUND: High intraoperative PEEP with recruitment manoeuvres may improve perioperative outcomes. We re-examined this question by conducting a patient-level meta-analysis of three clinical trials in adult patients at increased risk for postoperative pulmonary complications who underwent non-cardiothoracic and non-neurological surgery. METHODS: The three trials enrolled patients at 128 hospitals in 24 countries from February 2011 to February 2018. All patients received volume-controlled ventilation with low tidal volume. Analyses were performed using one-stage, two-level, mixed modelling (site as a random effect; trial as a fixed effect). The primary outcome was a composite of postoperative pulmonary complications within the first week, analysed using mixed-effect logistic regression. Pre-specified subgroup analyses of nine patient characteristics and seven procedure and care-delivery characteristics were also performed. RESULTS: Complete datasets were available for 1913 participants ventilated with high PEEP and recruitment manoeuvres, compared with 1924 participants who received low PEEP. The primary outcome occurred in 562/1913 (29.4%) participants randomised to high PEEP, compared with 620/1924 (32.2%) participants randomised to low PEEP (unadjusted odds ratio [OR]=0.87; 95% confidence interval [95% CI], 0.75-1.01; P=0.06). Higher PEEP resulted in 87/1913 (4.5%) participants requiring interventions for desaturation, compared with 216/1924 (11.2%) participants randomised to low PEEP (OR=0.34; 95% CI, 0.26-0.45). Intraoperative hypotension was associated more frequently (784/1913 [41.0%]) with high PEEP, compared with low PEEP (579/1924 [30.1%]; OR=1.87; 95% CI, 1.60-2.17). CONCLUSIONS: High PEEP combined with recruitment manoeuvres during low tidal volume ventilation in patients undergoing major surgery did not reduce postoperative pulmonary complications. CLINICAL TRIAL REGISTRATION: NCT03937375 (Clinicaltrials.gov).

Published
2022

9. Effects of oxygen on post-surgical infections during an individualised perioperative open-lung ventilatory strategy: a randomised controlled trial

Author

Daniel López-Herrera, Raluca Florea, Rosa Almajano, Inmaculada India, Gerardo Aguilar, Javier Hernández, Juan Carrizo, Antonio López, Rafael Cabadas, Manuel Ortega, Elena Del Río, Elizabeth Bárcena, Cristina Garcés, Maite Ibáñez, María José Alberola, Amalia Alcón, Rayco Rodríguez, Jesús Castillo, Rafael Anaya, Ferran Serralta, Victor Balandrón, Cristian Aragón, Santiago Pinol, M. Granell, Domingo González, Inés Imaz, Yessica Guerra, Laura Reviriego, Alejandro Duca, Rubén Villazala, Jara Torrente, Lola Ruiz, Jesús Acosta, Marina Soro, Lucas Rovira, Natalia Bejarano, Jaume Balust, Paula Duque, Jaume Puig, Carmen Fernández, Raquel Callejas, Vanesa Berges, Omar M. Montenegro, Lucia Gallego-Ligorit, Pablo Monedero, Juan Delgado, Graciela Martínez, Santiago Garcia Del Valle, Sergio Cabrera, Carlos Álvarez, Lorena Colomina, Ana Martín, Ernesto Pastor, Sara Visiedo, Laura Sancho, Isabel Fuentes, Rafael González, Alejandro Gracia, Enrique Alday, Beatriz García, Ana Colás, Paola Valls, Maria Guillén Bermejo, Ana Parera, Estefania Gracia, Carlos Ferrando, Gemma Echarri, Carlos Dexeus, Miriam Herrero, Gerardo Tusman, Irene León, Ana Perez, Sergio Sánchez, Patricia Cruz, Sonsoles Leal, Javier Cuervo, Pascual Martinez, Carlos R. Molina, Andrea Brunelli, Salomé Matoses, Francisco Sandín, Clara Gallego, Luis Belmonte, Aurelio Rodríguez, Sara Pérez, Fernando Gil, Marina Varela, Esperanza Mata, Blanca Romero, Francisco J Redondo, Eva Tres, Ana Jurado, Maria Garcia, Manuel de la Matta, Pablo Oliver-Forniés, Esther García, Julia Hernando, Natividad Quesada, Jose L. Muñoz, Marta Argilaga, María A. Palencia, Angels Lozano, Laura Lascorz, Blanca Arocas, Mercedes García, Laura Viguera, Benigno Rodríguez, Consuelo Rego, Abigail Villena, Rodrigo Molina, Pilar Forcada, Carmen Unzueta, Esther Romero, Viviana Varón, F. Javier Belda, Patricia Fabra, Gema Del Castillo, Julián Librero, Pedro Charco, Gonzalo Azparren, María Merino, Sara Martínez, Mar Felipe, Ana Ramón, Salvador Peiró, Ruben Díaz, Maria del Mar Pérez, Mandalina Dinu, Roger Pujol, José M. Marcos, Beatriz Garrigues, Laura Cotter, Begoña Ayas, Oscar Diaz-Cambronero, Andrea Gutierrez, Rosa Mendez, Natividad Pozo, Jose Ignacio García, Ana Mugarra, José A. Carbonell, Manuel López-Baamonde, Lucía Valencia, Guido Mazzirani, Blanca Izquierdo, Marta Roselló, Andrés Millaruelo, Berta Monleon, Cesar Aldecoa, Ignacio Garutti, Victor Vega, Noelia Lafuente, Jesús Villar, David Pestaña, Laura Vaquero, and Fernando Suarez-Sipmann

Subjects
Adult, Male, Pulmonary Atelectasis, recruitment manoeuvres, Context (language use), Atelectasis, Perioperative Care, law.invention, Positive-Pressure Respiration, sepsis, surgery, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, 030202 anesthesiology, law, Fraction of inspired oxygen, Intensive care, Abdomen, postoperative complications, medicine, Humans, Surgical Wound Infection, Precision Medicine, Aged, Aged, 80 and over, business.industry, inspiratory oxygen fraction, anaesthesia, Perioperative, Middle Aged, surgical site infection, medicine.disease, Respiration, Artificial, Oxygen, Clinical trial, Treatment Outcome, Anesthesiology and Pain Medicine, Oxyhemoglobins, Anesthesia, Female, business, positive end-expiratory pressure, Abdominal surgery
Abstract

Background We aimed to examine whether using a high fraction of inspired oxygen (FIO2) in the context of an individualised intra- and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery. Methods We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality. Results We enrolled 740 subjects: 371 in the high FIO2 group and 369 in the low FIO2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59–1.50; P=0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48–1.25; P=0.38) and myocardial ischaemia (0.6% [n=2] vs 0% [n=0]; P=0.47) did not differ between groups. Conclusions An oxygenation strategy using high FIO2 compared with conventional FIO2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found. Clinical trial registration NCT02776046.

Published
2020
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10. Label-Free Quantitative Proteomic Analysis of Nitrogen Starvation in Arabidopsis Root Reveals New Aspects of H2S Signaling by Protein Persulfidation

Author

Luis C. Romero, Ana Jurado-Flores, and Cecilia Gotor

Subjects
0106 biological sciences, 0301 basic medicine, autophagy, persulfidation, Hhydrogen sulfide, Physiology, Clinical Biochemistry, Arabidopsis, hydrogen sulfide, Endogeny, Protein degradation, 01 natural sciences, Biochemistry, 03 medical and health sciences, Cisteine, Autophagy, Arabidopsis thaliana, Molecular Biology, cysteine, proteomic, 2. Zero hunger, biology, Chemistry, lcsh:RM1-950, Proteomic, Cell Biology, biology.organism_classification, Cell biology, 030104 developmental biology, lcsh:Therapeutics. Pharmacology, Proteome, Persulfidation, Signal transduction, 010606 plant biology & botany, Cysteine
Abstract

Hydrogen sulfide (H2S)-mediated signaling pathways regulate many physiological and pathophysiological processes in mammalian and plant systems. The molecular mechanism by which hydrogen sulfide exerts its action involves the posttranslational modification of cysteine residues to form a persulfidated thiol motif. We developed a comparative and label-free quantitative proteomic analysis approach for the detection of endogenous persulfidated proteins in N-starved Arabidopsis thaliana roots by using the tag-switch method. In this work, we identified 5214 unique proteins from root tissue that were persulfidated, 1674 of which were quantitatively analyzed and found to show altered persulfidation levels in vivo under N deprivation. These proteins represented almost 13% of the entire annotated proteome in Arabidopsis. Bioinformatic analysis revealed that persulfidated proteins were involved in a wide range of biological functions, regulating important processes such as primary metabolism, plant responses to stresses, growth and development, RNA translation and protein degradation. Quantitative mass spectrometry analysis allowed us to obtain a comprehensive view of hydrogen sulfide signaling via changes in the persulfidation levels of key protein targets involved in ubiquitin-dependent protein degradation and autophagy, among others

Published
2021

11. Factors associated with poor anticoagulation control with vitamin K antagonists among outpatients attended in Internal Medicine and Neurology. The ALADIN study

Author

Cristina Barbagelata, Francisco Cabrera, María Herrera, Pedro Cardona, Radka Ivanova Georgieva, José Miguel Pons, Maite Martínez, Jesús Saiz, Tomás Pérez, José Ángel Satué, Cristina Tejera Pérez, Joan Rosal, Javier Fernández, M. José Gómez, Jordi Sanahuja, Patricia Ibáñez, Ana Rodríguez, José M. Errea, Alejandro Martínez-Domeño, Antonio Manquillo, Ana Latorre, Luis Beltrán, Juli Font, Cecile van Eedenburg, Xavier Ustrell, Elena Bello, Raquel González, M. Carmen Gil, José Antonio Díaz, Francisco Purroy, Elena Calzado, José Carlos Gómez, Susana Arias, Clara Sainz, Óscar Fabre, Francisco Javier Barrero, José Ferreiro, José M. Ramírez-Moreno, Mariano Aguayo, Lamberto Landete, Manuel Rodríguez, Ramón Villaverde, Eduardo Agüera-Morales, C. Suárez Fernández, José Ramírez, Gemma Reig, Covadonga Fernández, Carmen Jiménez, Ana M Roa, Alejandro Ponz, Joaquín Carnedo, Rafael Fernández de la Puerta, Jerzy Kuprinski, Raquel Chamarro, Enrique Cabrerizo, Rafael López, M. Ángeles Revilla, Xavier Nogués, Marta Serrano, Roberto Muñoz, José M. Trejo, Jaume Roquer, Beatriz Zandio, María Pérez de la Blanca, Santiago Montull, Helena Quesada, Juan Carlos Anglada, Ana de Arce, Ana Pampliega, Juan Carlos Belinchón, Jaime Gállego, Francisco Moniche, Inmaculada Villegas, Nuria Aymerich, Juan José Mengual, Ana Calleja, Antonio Gil-Núñez, Antonio Medina, Fernando Salgado, Antonio Pose, Blanca Batalla, Sandra Boned-Riera, Juan José Cara, José M. Terrero, Juan Luengo, Román Cerro, José Tembl, Laia Seró, Christian Homedes, Manuel Payan, Imma Cañas, Blanca Fuentes, Fernando Díaz, Laura Ballester, Francisco Lozano, Ignacio Casado, M. Pilar Moreno, Luis López, Antonio Arjona, Miguel Yebra, Jorge Romero, Marco Antonio Budiño, Francesc Puchades, Jacinto Hernández, Javier García, María Concepción Prados Sánchez, Joan Martí-Fàbregas, José Castro, M. Ángeles Fidalgo, Javier Marta, Alicia de Felipe, David Esteva, María Bestué, Vicente Oliver, Marta Guillan, David Vinuesa García, Esther Aragón, Natividad Raña, José Maciñeiras, José Luis Vázquez, Juan Carlos Martínez-Acitores, Dolores Fernández, Félix González, Demetrio Sánchez, Rafael Bustamante, María Ángeles Ortega, Nuria Navarrete, Jesús M. Juega, Emilio Barroso, Pedro Luis Muñoz, Leticia Álvarez, Mónica Arias, Carlos Sánchez, Juan Antonio Arroyo, Juan José Timiraos, Ana Jurado, José Carlos Pontes, Sonia M. García, Iluminada García Polo, Daniel Irigoyen, Arturo Artero, Maria Àngels Font, Miguel Ángel Rico, Laura Imaz, Salvadora Martínez, José Carlos Fernández, Ikram Benabdelhak, Ana María González, Patricia Martínez, Sonia Huertas, Francisco Javier Martínez, Yolanda Bravo, Alfonso Aguirre, Luis Mérida, Carlos Tejero, Jordi Espinosa, Montserrat González, Consuelo Matute, José M. de Lis, Marian Muchada, José Bernardo Escribano, M. Dolores Moragues, Miguel Ángel Corrales, Mar Freijo, Juan F. Arenillas, J. Manuel Cerqueiro, Aida Lago, Manuel Montero, Enrique Mostacero, Javier de la Torre, Jesús Foronda, David Gorriz, Óscar Fernández, Elisa Rodríguez, Alex Culla, José M. Rivera, Juan Carlos Portilla, Roberto Pérez, Marta Pena, Bárbara Vives, Julián Fernández, Jose Antonio Egido, Ana Castellano, Mónica Zamora, Agustín Pijierro, Eva Calvo, Elisa Cortijo, Fernando Aguilar, David Cánovas, José Vivancos, Pablo Irimia, Enrique Calderón, Carlos Molina, Pedro Jesús Serrano, Esther Fernández, J. Tejada, Carmen Morata, María Paz Martínez, Gerardo Ruiz, César Lucas, Purificación Durán, Ángel Ois, Noemí Díez, José Antonio Tamayo, Jordi Casanova, Igor Molina, Jaime Díaz, Carmen Caro, Susana Mederer, Fernando Jaén, Jordi Estela, Dionisio Carrillo, Irene Navalpotro, José Luis Beato Pérez, Alain Luna, Jorge Artal, Jesús Cantero, Enrique Palacio, Elisa Cuadrado, Javier Reyes, Pilar Meler, Miguel Alberto de Zarraga, Gema Sanz, M. Ángeles López, Ricardo Gómez, Joaquín Sánchez, Miguel Ángel García, Raúl Quirós, Rosario Gil, Héctor Guerrero, Jorge Marrero, Eduardo Carmona, José Carlos Morán, José Antonio Trujillo, Alan Flores, Juan Manuel García, Manuel Gómez-Choco, Amparo Romero, Carlos Vilar, Santiago Freire, M. del Mar Castellanos, Silvia Tur, Cristina Borrachero, Jesús Vega, Sonia Gonzalo, Alberto Morán, Laura Ramos, Antonio Cayon, Manuel Seijo, Raquel Delgado-Mederos, M. José Fonseca, Juan Girón, Aida Rodríguez, Yesica Miranda, Jaime Masjuan, Álvaro González, Iván Moreno, Fernando Sierra, Jordi Jiménez, M. del Carmen Riveira, Davinia Larrosa, Rosa Díaz, Daniel Peña, M.M. Contreras Muruaga, Joaquín Antón, Irene Escudero, Borja Enrique Sanz, and Antoni German

Subjects
medicine.medical_specialty, Acenocoumarol, Neurology, business.industry, Warfarin, Atrial fibrillation, General Medicine, 030204 cardiovascular system & hematology, Vitamin k, medicine.disease, Thromboembolic risk, 03 medical and health sciences, 0302 clinical medicine, Multicenter study, Diabetes mellitus, Internal medicine, medicine, 030212 general & internal medicine, business, medicine.drug
Abstract

Objective To identify factors associated with poor anticoagulation control with vitamin K antagonists (VKA) among outpatients with nonvalvular atrial fibrillation (NVAF) attended in Neurology and Internal Medicine in Spain. Methods Cross-sectional and multicenter study, from the ALADIN database, of outpatients with NVAF treated with VKA and attended in Internal Medicine and Neurology in Spain. Rates of anticoagulation control were determined with the direct and Rosendaal methods, considering data from the 6 months before the inclusion. Results Out of 1337 patients included in the ALADIN study, 750 were taking VKA, and complete information about INR values in the last 6 months was available in 383 patients. Mean scores of Charlson Index, CHADS2, CHA2DS2-VASc and HAS-BLED were 1.94 ± 1.54; 3.10 ± 1.26; 4.63 ± 1.54, and 2.20 ± 0.90, respectively. 46.2% and 47.0% of patients had an adequate anticoagulation control according to the direct and Rosendaal methods, respectively. Inadequate anticoagulation control according to the direct method was associated with diabetes (OR: 2.511; 95% CI: 1.144–5.659), prior labile INR (OR: 35.371; 95% CI: 15.058–83.083) and the determination of >6 INR controls in the last 6 months (OR: 4.747; 95% CI: 2.094–10.759), and according to the Rosendaal method, with prior labile INR (p Conclusions Despite the high thromboembolic risk, only a little more than a half of patients were well controlled. Factors associated with poor anticoagulation control were diabetes, labile INR, >6 INR controls and HAS-BLED.

Published
2018
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12. Factores asociados al mal control de la anticoagulación con antivitamina K en pacientes con fibrilación auricular no valvular atendidos en consultas de Medicina Interna y Neurología. Estudio ALADIN

Author

M.M. Contreras Muruaga, G. Reig, J. Vivancos, A. González, P. Cardona, J.M. Ramírez-Moreno, J. Martí-Fábregas, C. Suárez Fernández, Antonio Pose, José Antonio Díaz, Manuel Rodríguez, Marta Pena, Susana Arias, Davinia Larrosa, Álvaro González, Elisa Rodríguez, Montserrat González, Dolores Fernández, Cristina Barbagelata, Natividad Raña, Santiago Freire, J. Manuel Cerqueiro, Héctor Guerrero, Laura Ramos, Leticia Álvarez, José M. de Lis, Carmen Caro, Manuel Seijo, Susana Mederer, Miguel Alberto de Zarraga, José Ferreiro, José M. Terrero, Mónica Arias, Roberto Pérez, Joaquín Sánchez, José Maciñeiras, Julián Fernández, Fernando Jaén, David Esteva, Mónica Zamora, Nuria Navarrete, Javier García, Luis Mérida, Miguel Ángel Corrales, Raúl Quirós, Jesús Cantero, Francisco Javier Barrero, Inmaculada Villegas, José Castro, Jesús Foronda, Dionisio Carrillo, Jesús Vega, José Antonio Trujillo, Manuel Montero, Ana Jurado, Carlos Sánchez, Eduardo Agüera-Morales, María Sánchez, Purificación Durán, Rafael Fernández de la Puerta, María Pérez de la Blanca, María Paz Martínez, Óscar Fernández, José Antonio Tamayo, Rafael Bustamante, Pedro Jesús Serrano, Antonio Arjona, Javier Fernández, Manuel Payan, Ricardo Gómez, Daniel Peña, Enrique Cabrerizo, Fernando Salgado, Radka Ivanova Georgieva, Antonio Gil-Núñez, Elena Bello, Fernando Díaz, Antonio Medina, Ana Castellano, Yesica Miranda, Óscar Fabre, Iluminada García Polo, Patricia Ibáñez, Clara Sainz, Fernando Sierra, Esther Aragón, Jaime Díaz, Fernando Aguilar, María Ángeles Ortega, José Antonio Egido, José Carlos Pontes, Miguel Ángel García, Francisco Cabrera, Blanca Batalla, Alex Culla, Carlos Molina, Alan Flores, Laia Seró, Marian Muchada, Pilar Meler, Sandra Boned-Riera, David Cánovas, Jordi Estela, Juli Font, Francisco Purroy, Ikram Benabdelhak, Jordi Sanahuja, Jaume Roquer, Ana Rodríguez, Ángel Ois, Elisa Cuadrado, Jordi Jiménez, Xavier Nogués, Jerzy Kuprinski, Antoni German, Daniel Irigoyen, Juan José Cara, Maria Àngels Font, Sonia Huertas, Alejandro Martínez-Domeño, Juan Antonio Arroyo, Raquel Delgado-Mederos, Manuel Jesús Gómez-Choco, Juan José Mengual, Sonia M. García, M. del Mar Castellanos, Cecile van Eedenburg, Imma Cañas, Jordi Espinosa, Santiago Montull, Helena Quesada, Xavier Ustrell, Christian Homedes, Irene Navalpotro, Jordi Casanova, Aida Pilar Lago, Carmen Morata, David Gorriz, Iván Moreno, José Tembl, Alejandro Ponz, M. José Fonseca, Raquel Chamarro, Rosario Gil, Vicente Oliver, Ana Pampliega, Arturo Artero, Francesc Puchades, Lamberto Landete, Carlos Vilar, Carmen Jiménez, Bárbara Vives, M. Dolores Moragues, Rosa Díaz, Silvia Tur, José Bernardo Escribano, César Lucas, Francisco Martínez, José Miguel Pons, Amparo Romero, David García, José Pérez, Ramón Villaverde, Salvadora Martínez, Aida Rodríguez, Carlos Tejero, Cristina Pérez, Enrique Mostacero, Covadonga Fernández, Alain Luna, Tomás Pérez, Félix González, Ana de Arce, Maite Martínez, Noemí Díez, Jaime Gállego, Beatriz Zandio, María Herrera, Nuria Aymerich, Roberto Muñoz, Javier Marta, Jorge Artal, José M. Errea, Juan José Timiraos, M. Pilar Moreno, Mar Freijo, Juan Manuel García, M. Carmen Gil, M. Ángeles Revilla, Enrique Palacio, José Luis Vázquez, María Bestué, Ana Latorre, Eva Calvo, Laura Ballester, Marta Serrano, Jesús M. Juega, M. Ángeles López, Pablo Irimia, Laura Imaz, Blanca Fuentes, Borja Enrique Sanz, Luis Beltrán, Gerardo Ruiz, Patricia Martínez, Demetrio Sánchez, Emilio Barroso, Igor Molina, Marco Antonio Budiño, Jaime Masjuan, Alicia de Felipe, Consuelo Matute, Javier Tejada, Alberto Morán, Esther Fernández, M. del Carmen Riveira, Joaquín Carnedo, Antonio Manquillo, Raquel González, José Carlos Fernández, Marta Guillan, Miguel Yebra, José M. Trejo, Jesús Saiz, Juan Carlos Martínez-Acitores, Yolanda Bravo, Juan Francisco Arenillas, Ana Calleja, Elisa Cortijo, Javier Reyes, Luis López, Pedro Luis Muñoz, M. Ángeles Fidalgo, Jacinto Hernández, José Carlos Gómez, José Carlos Morán, Sonia Gonzalo, Jorge Marrero, José Ángel Satué, Juan Carlos Belinchón, Francisco Moniche, Enrique Calderón, Irene Escudero, Javier de la Torre, Ignacio Casado, Joaquín Antón, Juan Carlos Portilla, Juan Luengo, Joan Rosal, Elena Calzado, Juan Carlos Anglada, Juan Girón, José M. Ramírez, Agustín Pijierro, Ana Roa, Jorge Romero, Mariano Aguayo, Cristina Borrachero, Gema Sanz, M. José Gómez, Miguel Ángel Rico, Antonio Cayon, Eduardo Carmona, Román Cerro, Rafael López, Alfonso Aguirre, Francisco Lozano, and José M. Rivera.

Subjects
03 medical and health sciences, 0302 clinical medicine, business.industry, Medicine, 030212 general & internal medicine, General Medicine, 030204 cardiovascular system & hematology, business, Humanities
Abstract

Resumen Objetivo Identificar los factores asociados con el mal control de la anticoagulacion con antagonistas de la vitamina K (AVK) en pacientes con fibrilacion auricular no valvular (FANV) atendidos en consultas de Neurologia y Medicina Interna de Espana. Metodos Estudio transversal, multicentrico, anidado en el estudio ALADIN, de sujetos con FANV, tratados con AVK, atendidos en consultas de Medicina Interna o Neurologia de Espana. El grado de control de la anticoagulacion se estudio mediante el metodo directo y el de Rosendaal, considerando los 6 meses previos a la inclusion. Resultados De los 1.337 pacientes incluidos en ALADIN, 750 estaban tratados con AVK, con informacion completa sobre el INR de los ultimos 6 meses en 383 pacientes. Las puntuaciones medias del indice de Charlson, CHADS2, CHA2DS2-VASc y HAS-BLED fueron 1,94 ± 1,54; 3,10 ± 1,26; 4,63 ± 1,54 y 2,20 ± 0,90, respectivamente. El 46,2% y el 47,0% de los pacientes presentaban un control adecuado de la anticoagulacion por los metodos directo y Rosendaal, respectivamente. El control inadecuado de la anticoagulacion se asocio por el metodo directo con diabetes (OR: 2,511; IC 95%: 1,144-5,659), antecedentes de INR inestable (OR: 35,371; IC 95%: 15,058-83,083) y la realizacion de > 6 controles en los ultimos 6 meses (OR: 4,747; IC 95%: 2,094-10,759), y por el metodo de Rosendaal, con los antecedentes de INR inestable (p Conclusiones Pese al alto riesgo tromboembolico, solo estaban bien controlados algo mas de la mitad. Los factores asociados al mal control de la anticoagulacion fueron la diabetes, INR inestable, > 6 controles de INR y el HAS-BLED.

Published
2018
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13. Abscisic acid-triggered persulfidation of the cys protease ATG4 mediates regulation of autophagy by sulfide

Author

Luis C. Romero, José L. Crespo, Inmaculada Yruela, Cecilia Gotor, Ana Jurado-Flores, M. Esther Pérez-Pérez, Angeles Aroca, Inmaculada Moreno, Ana M. Laureano-Marín, European Commission, Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), Junta de Andalucía, Gobierno de Aragón, Yruela Guerrero, Inmaculada [0000-0003-3608-4720], Yruela Guerrero, Inmaculada, and Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular

Subjects
Proteomics, 0106 biological sciences, 0301 basic medicine, Proteases, Sulfide, Nitrogen, Hydrogen sulfide, medicine.medical_treatment, Arabidopsis, Autophagy-Related Proteins, Plant Science, Sulfides, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, Cysteine Proteases, Autophagy, medicine, Arabidopsis thaliana, Research Articles, chemistry.chemical_classification, Reactive oxygen species, Protease, biology, Arabidopsis Proteins, Cell Biology, biology.organism_classification, 3. Good health, Cell biology, 030104 developmental biology, chemistry, Reactive Oxygen Species, Abscisic Acid, Signal Transduction, 010606 plant biology & botany
Abstract

48 Pags.- 10 Figs. The definitive version, with suppl mat., is available at: http://www.plantcell.org/, Hydrogen sulfide is a signaling molecule that regulates essential processes in plants, such as autophagy. In Arabidopsis (Arabidopsis thaliana), hydrogen sulfide negatively regulates autophagy independently of reactive oxygen species via an unknown mechanism. Comparative and quantitative proteomic analysis was used to detect abscisic acid-triggered persulfidation that reveals a main role in the control of autophagy mediated by the autophagy-related (ATG) Cys protease AtATG4a. This protease undergoes specific persulfidation of Cys170 that is a part of the characteristic catalytic Cys-His-Asp triad of Cys proteases. Regulation of the ATG4 activity by persulfidation was tested in a heterologous assay using the Chlamydomonas reinhardtii CrATG8 protein as a substrate. Sulfide significantly and reversibly inactivates AtATG4a. The biological significance of the reversible inhibition of the ATG4 by sulfide is supported by the results obtained in Arabidopsis leaves under basal and autophagy-activating conditions. A significant increase in the overall ATG4 proteolytic activity in Arabidopsis was detected under nitrogen starvation and osmotic stress and can be inhibited by sulfide. Therefore, the data strongly suggest that the negative regulation of autophagy by sulfide is mediated by specific persulfidation of the ATG4 protease., This work was supported in part by the European Regional Development Fund through the Ministerio de Economía y Competitividad and the Agencia Estatal de Investigación (grant nos. BFU2015-68216-P and PGC2018-099048- B-I00 to J.L.C.; grant nos. BIO2015-74432-JIN and PID2019- 110080GB-I00 to M.E.P.-P.; grant nos. BIO2016-76633-P and PID2019- 109785GB-I00; and Junta de Andalucía grant no. P18-RT-3154 to C.G.)., the Marie Skłodowska-Curie Grant Agreement (grant no. 834120 to Á.A.), Government of Aragón-FEDER (grant no. E35_17R to I.Y.), and the Ministerio de Economia y Competitividad through the program of “Formación de Personal Investigador” (to A.M.L.-M. and A.J.-F.).

Published
2020

14. Exploring the Functional Relationship between y-Type Thioredoxins and 2-Cys Peroxiredoxins in Arabidopsis Chloroplasts

Author

Leonor Puerto-Galán, Francisco Javier Cejudo, Ana Jurado-Flores, Juan Manuel Pérez-Ruiz, Víctor Delgado-Requerey, Alicia Gálvez-Ramírez, and Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular

Subjects
0106 biological sciences, 0301 basic medicine, Gene isoform, Physiology, Clinical Biochemistry, Mutant, thioredoxin y, Thioredoxin r, 01 natural sciences, Biochemistry, Chloroplast, 2-Cys peroxiredoxin, 03 medical and health sciences, Arabidopsis, Thioredoxin x, thioredoxin x, Thioredoxin y, NTRC, Photosynthesis, Molecular Biology, Ferredoxin, chemistry.chemical_classification, biology, Chemistry, Stress response, lcsh:RM1-950, Cell Biology, Metabolism, biology.organism_classification, Phenotype, Cell biology, 030104 developmental biology, Enzyme, lcsh:Therapeutics. Pharmacology, Redox regulation, 010606 plant biology & botany
Abstract

Thioredoxins (Trxs) are small, ubiquitous enzymes that catalyze disulphide–dithiol interchange in target enzymes. The large set of chloroplast Trxs, including f, m, x and y subtypes, use reducing equivalents fueled by photoreduced ferredoxin (Fdx) for fine-tuning photosynthetic performance and metabolism through the control of the activity of redox-sensitive proteins. Although biochemical analyses suggested functional diversity of chloroplast Trxs, genetic studies have established that deficiency in a particular Trx subtype has subtle phenotypic e ects, leading to the proposal that the Trx isoforms are functionally redundant. In addition, chloroplasts contain an NADPH-dependent Trx reductase with a joint Trx domain, termed NTRC. Interestingly, Arabidopsis mutants combining the deficiencies of x- or f-type Trxs and NTRC display very severe growth inhibition phenotypes, which are partially rescued by decreased levels of 2-Cys peroxiredoxins (Prxs). These findings indicate that the reducing capacity of Trxs f and x is modulated by the redox balance of 2-Cys Prxs, which is controlled by NTRC. In this study, we explored whether NTRC acts as a master regulator of the pool of chloroplast Trxs by analyzing its functional relationship with Trxs y. While Trx y interacts with 2-Cys Prxs in vitro and in planta, the analysis of Arabidopsis mutants devoid of NTRC and Trxs y suggests that Trxs y have only a minor e ect, if any, on the redox state of 2-Cys Prxs.

Published
2020

15. Signaling by hydrogen sulfide and cyanide through post-translational modification

Author

Lucía Arenas-Alfonseca, Ana M. Laureano-Marín, Luis C. Romero, Cecilia Gotor, Inmaculada Moreno, Ana Jurado-Flores, Irene García, and Angeles Aroca

Subjects
chemistry.chemical_classification, Cyanides, Sulfide, Physiology, Arabidopsis Proteins, Cyanide, Hydrogen sulfide, Hydrogen cyanide, Arabidopsis, Plant Science, Root hair elongation, Sulfite reductase, chemistry.chemical_compound, chemistry, Biophysics, Hydrogen Sulfide, Mode of action, Protein Processing, Post-Translational, Cysteine, Signal Transduction
Abstract

Two cysteine metabolism-related molecules, hydrogen sulfide and hydrogen cyanide, which are considered toxic, have now been considered as signaling molecules. Hydrogen sulfide is produced in chloroplasts through the activity of sulfite reductase and in the cytosol and mitochondria by the action of sulfide-generating enzymes, and regulates/affects essential plant processes such as plant adaptation, development, photosynthesis, autophagy, and stomatal movement, where interplay with other signaling molecules occurs. The mechanism of action of sulfide, which modifies protein cysteine thiols to form persulfides, is related to its chemical features. This post-translational modification, called persulfidation, could play a protective role for thiols against oxidative damage. Hydrogen cyanide is produced during the biosynthesis of ethylene and camalexin in non-cyanogenic plants, and is detoxified by the action of sulfur-related enzymes. Cyanide functions include the breaking of seed dormancy, modifying the plant responses to biotic stress, and inhibition of root hair elongation. The mode of action of cyanide is under investigation, although it has recently been demonstrated to perform post-translational modification of protein cysteine thiols to form thiocyanate, a process called S-cyanylation. Therefore, the signaling roles of sulfide and most probably of cyanide are performed through the modification of specific cysteine residues, altering protein functions.

Published
2019

16. Individualised perioperative open-lung approach versus standard protective ventilation in abdominal surgery (iPROVE): a randomised controlled trial

Author

Rubén Villazala, Victoria Moral, Nazario Ojeda, Andrea Gutierrez, Tania Socorro, Inmaculada India, Angels Lozano, Ana Mugarra, Natividad Pozo, Jose Ignacio García, María Dolores Alonso, Ernesto Pastor, Amanda Miñana, Ana Isabel Galve, Elena Lozano, Eduardo Llamazares, Gonzalo Azparren, Ana Parera, Lucas Rovira, Rafael González, Luis Olmedilla, José I. Navarro, Javier Contreras García, Carolina Romero, Abigail Villena, Julián Librero, David Pestaña, Mercedes García, Cristina Parrilla, Isabel Fuentes, Carmen Fernández, Pedro Charco, Lucía Gallego, Jesús Acosta, Maria Del Barrio, Cristina Garcés, Maite Ibáñez, Nuria Garcia, Salvador Peiró, Javier Ignacio Román, Elena Del Río, Sergio Sánchez, Lorena Muñoz, Amalia Alcón, Carmen Unzueta, Roger Pujol, Cesar Aldecoa, Maria Garcia, Lucía Valencia, Estefanía Chamorro, Clara Gallego, Jesús Rico-Feijoo, María Pilar Argente, Laura Soriano, Fernando Díez, Inmaculada Benítez, Andrea Brunelli, Natalia Peña, Vicente Torres, María Asunción Parra, Alicia Llombart, Samuel Hernández, Gerardo Aguilar, Patricia Piñeiro, Albert Carramiñana, Ferran Serralta, Ignacio Garutti, Jose M. Alonso, Beatriz Garrigues, Gerardo Tusman, Irene León, Marta Giné, Patricia Cruz, Antonio Katime, Ana Asensio, Esther Romero, Francisco Daviu, Susana Díaz, Jonathan Olmedo, Viviana Varón, Sara Zapatero, María José Alberola, Francisco J Redondo, Cristina Lisbona, Isabel Ruiz, Tania Moreno, Pablo Garcia, Ana Izquierdo, Jesús Villar, Alberto Gallego-Casilda, Blanca Arocas, Begoña Ayas, Jaume Puig, José A. Carbonell, Oto Padrón, Marina Soro, Ester Sánchez, Natalia Bejarano, Oscar Diaz-Cambronero, Ruben Díaz, María Vila, Ana María Pérez, Francisco Sandín, Ramiro López, Estefania Gracia, Manuel Tisner, Virginia Cegarra, María Hernández, Jaume Canet, Graciella Martínez-Pallí, José M. Marcos, Angeles de Miguel, Jaume Balust, Laura Vaquero, Sergio Cabrera, Fernando Suarez-Sipmann, Daniel López-Herrera, Juan Carrizo, Mercedes Ayuso, Nilda Martínez, Silvia Martín, Rayco Rodríguez, Rafael Anaya, Jose María Pérez, Rosa Lardies, M. Granell, Domingo González, Inmaculada Hernández, Rosa Dosdá, Carlos Ferrando, Carlos Delgado, Mario De Fez, Santiago García-del-Valle, Ana Jurado, Guido Mazzinari, Paola Valls, Marta Agilaga, Antonio Romero, Victor Balandrón, Alejandro Duca, Rocío Martínez, Francisco Barrios, Ma Justina Etulain, Tania Franco, Vicente Gilabert, Laura Piqueras, Aurelio Rodríguez, Javier Belda, Lisset Miguel, José Valdivia, Ana Colás, and Manuel de la Matta

Subjects
Male, Pulmonary and Respiratory Medicine, medicine.medical_treatment, Population, Perioperative Care, law.invention, Positive-Pressure Respiration, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Randomized controlled trial, 030202 anesthesiology, law, Oxygen therapy, Abdomen, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Continuous positive airway pressure, education, Lung, Aged, Mechanical ventilation, education.field_of_study, business.industry, Perioperative, Middle Aged, Respiration, Artificial, respiratory tract diseases, Treatment Outcome, Spain, Anesthesia, Breathing, Female, business, Abdominal surgery
Abstract

Background The effects of individualised perioperative lung-protective ventilation (based on the open-lung approach [OLA]) on postoperative complications is unknown. We aimed to investigate the effects of intraoperative and postoperative ventilatory management in patients scheduled for abdominal surgery, compared with standard protective ventilation. Methods We did this prospective, multicentre, randomised controlled trial in 21 teaching hospitals in Spain. We enrolled patients who were aged 18 years or older, were scheduled to have abdominal surgery with an expected time of longer than 2 h, had intermediate-to-high-risk of developing postoperative pulmonary complications, and who had a body-mass index less than 35 kg/m(2). Patients were randomly assigned (1: 1: 1: 1) online to receive one of four lung-protective ventilation strategies using low tidal volume plus positive end-expiratory pressure (PEEP): open-lung approach (OLA)-iCPAP (individualised intraoperative ventilation [individualised PEEP after a lung recruitment manoeuvre] plus individualised postoperative continuous positive airway pressure [CPAP]), OLA-CPAP (intraoperative individualised ventilation plus postoperative CPAP), STD-CPAP (standard intraoperative ventilation plus postoperative CPAP), or STD-O-2 (standard intraoperative ventilation plus standard postoperative oxygen therapy). Patients were masked to treatment allocation. Investigators were not masked in the operating and postoperative rooms; after 24 h, data were given to a second investigator who was masked to allocations. The primary outcome was a composite of pulmonary and systemic complications during the first 7 postoperative days. We did the primary analysis using the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02158923. Findings Between Jan 2, 2015, and May 18, 2016, we enrolled 1012 eligible patients. Data were available for 967 patients, whom we included in the final analysis. Risk of pulmonary and systemic complications did not differ for patients in OLA-iCPAP (110 [46%] of 241, relative risk 0.89 [95% CI 0.74-1.07; p=0.25]), OLA-CPAP (111 [47%] of 238, 0.91 [0.76-1.09; p=0.35]), or STD-CPAP groups (118 [48%] of 244, 0.95 [0.80-1.14; p=0.65]) when compared with patients in the STD-O-2 group (125 [51%] of 244). Intraoperatively, PEEP was increased in 69 (14%) of patients in the standard perioperative ventilation groups because of hypoxaemia, and no patients from either of the OLA groups required rescue manoeuvres. Interpretation In patients who have major abdominal surgery, the different perioperative open lung approaches tested in this study did not reduce the risk of postoperative complications when compared with standard lung-protective mechanical ventilation.

Published
2018

17. The accuracy of postoperative, non-invasive Air-Test to diagnose atelectasis in healthy patients after surgery: a prospective, diagnostic pilot study

Author

José I. Navarro, Francisco Javier Belda, Ferran Serralta, Cristina Parrilla, Jesús Villar, Paola Valls, Natividad Pozo, Fernando Suarez-Sipmann, José E. Romero, Carolina Romero, Rosa Dosdá, Carlos Ferrando, Abigail Villena, Jaume Canet, Ana Jurado, Gerardo Tusman, Juan Carrizo, and Marina Soro

Subjects
Male, Diagnostic accuracy, Atelectasis, Pilot Projects, Anaesthesia, Tertiary Care Centers, 0302 clinical medicine, Postoperative Complications, 030202 anesthesiology, Postoperative atelectasis, atelectasis, postoperative, Oximetry, Prospective Studies, adult anaesthesia, False Negative Reactions, Breathing room air, Air, General Medicine, Middle Aged, Peripheral, Capillary oxygen saturation, Anesthesia, Female, oxygenation, Adult, medicine.medical_specialty, Pulmonary Atelectasis, Anestesi och intensivvård, Anesthesia, General, Sensitivity and Specificity, 03 medical and health sciences, medicine, Humans, adult intensive & critical care, Aged, Anesthesiology and Intensive Care, business.industry, Research, fungi, Non invasive, Oxygen Inhalation Therapy, 030208 emergency & critical care medicine, Oxygenation, medicine.disease, Surgery, SpO2, Spain, Linear Models, Blood Gas Analysis, business, Tomography, X-Ray Computed
Abstract

Objective To assess the diagnostic accuracy of peripheral capillary oxygen saturation (SpO(2)) while breathing room air for 5 min (the 'Air-Test') in detecting postoperative atelectasis. Design Prospective cohort study. Diagnostic accuracy was assessed by measuring the agreement between the index test and the reference standard CT scan images. Setting Postanaesthetic care unit in a tertiary hospital in Spain. Participants Three hundred and fifty patients from 12 January to 7 February 2015; 170 patients scheduled for surgery under general anaesthesia who were admitted into the postsurgical unit were included. Intervention The Air-Test was performed in conscious extubated patients after a 30 min stabilisation period during which they received supplemental oxygen therapy via a venturi mask. The Air-Test was defined as positive when SpO(2) was >= 96% and negative when SpO(2) was >= 97%. Arterial blood gases were measured in all patients at the end of the Air-Test. In the subsequent 25 min, the presence of atelectasis was evaluated by performing a CT scan in 59 randomly selected patients. Main outcome measures The primary study outcome was assessment of the accuracy of the Air-Test for detecting postoperative atelectasis compared with the reference standard. The secondary outcome was the incidence of positive Air-Test results. Results The Air-Test diagnosed postoperative atelectasis with an area under the receiver operating characteristic curve of 0.90 (95% CI 0.82 to 0.98) with a sensitivity of 82.6% and a specificity of 87.8%. The presence of atelectasis was confirmed by CT scans in all patients (30/30) with positive and in 5 patients (17%) with negative Air-Test results. Based on the Air-Test, postoperative atelectasis was present in 36% of the patients (62 out of 170). Conclusion The Air-Test may represent an accurate, simple, inexpensive and non-invasive method for diagnosing postoperative atelectasis.

Published
2017

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