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28 results on '"Marianna Esposito"'

1. Use of Lung Ultrasound in Cystic Fibrosis: Is It a Valuable Tool?

Author

Alessandra Boni, Luca Cristiani, Fabio Majo, Nicola Ullmann, Marianna Esposito, Maria Chiara Supino, Paolo Tomà, Alberto Villani, Anna Maria Musolino, and Renato Cutrera

Subjects
lung ultrasound, cystic fibrosis, management, pulmonary exacerbations, follow-up, bronchiectasis, Pediatrics, RJ1-570
Abstract

Cystic fibrosis (CF) is a multisystem disorder characterized by progressive respiratory deterioration, significantly impacting both quality of life and survival. Over the years, lung ultrasound (LUS) has emerged as a promising tool in pediatric respiratory due to its safety profile and ease at the bedside. In the era of highly effective CF modulator therapies and improved life expectancy, the use of non-ionizing radiation techniques could become an integral part of CF management, particularly in the pediatric population. The present review explores the potential role of LUS in CF management based on available data, analyzing all publications from January 2015 to January 2024, focusing on two key areas: LUS in CF pulmonary exacerbation and its utility in routine clinical management. Nonetheless, LUS exhibits a robust correlation with computed tomography (CT) scans and serves as an additional, user-friendly imaging modality in CF management, demonstrating high specificity and sensitivity in identification, especially in consolidations and atelectasis in the CF population. Due to its ability, LUS could be an instrument to monitor exacerbations with consolidations and to establish therapy duration and monitor atelectasis over time or their evolution after therapeutic bronchoalveolar lavage. On the basis of our analysis, sufficient data emerged showing a good correlation between LUS score and respiratory function tests. Good sensitivity and specificity of the methodology have been found in rare CF pulmonary complications such as effusion and pneumothorax. Regarding its use in follow-up management, the literature reports a moderate correlation between LUS scores and the type, extent, and CT severity score of bronchiectasis. A future validation of ultrasound scores specifically in CF patients could improve the use of LUS to identify pulmonary exacerbations and monitor disease progression. However, further research is needed to comprehensively establish the role of LUS in the CF population, particularly in elucidating its broader utility and long-term impact on patient care.

Published
2024
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2. Cancer cells adapt FAM134B/BiP mediated ER-phagy to survive hypoxic stress

Author

Sandhya Chipurupalli, Raja Ganesan, Giulia Martini, Luigi Mele, Alessio Reggio, Marianna Esposito, Elango Kannan, Vigneshwaran Namasivayam, Paolo Grumati, Vincenzo Desiderio, and Nirmal Robinson

Subjects
Cytology, QH573-671
Abstract

Abstract In the tumor microenvironment, cancer cells experience hypoxia resulting in the accumulation of misfolded/unfolded proteins largely in the endoplasmic reticulum (ER). Consequently, ER proteotoxicity elicits unfolded protein response (UPR) as an adaptive mechanism to resolve ER stress. In addition to canonical UPR, proteotoxicity also stimulates the selective, autophagy-dependent, removal of discrete ER domains loaded with misfolded proteins to further alleviate ER stress. These mechanisms can favor cancer cell growth, metastasis, and long-term survival. Our investigations reveal that during hypoxia-induced ER stress, the ER-phagy receptor FAM134B targets damaged portions of ER into autophagosomes to restore ER homeostasis in cancer cells. Loss of FAM134B in breast cancer cells results in increased ER stress and reduced cell proliferation. Mechanistically, upon sensing hypoxia-induced proteotoxic stress, the ER chaperone BiP forms a complex with FAM134B and promotes ER-phagy. To prove the translational implication of our mechanistic findings, we identified vitexin as a pharmacological agent that disrupts FAM134B-BiP complex, inhibits ER-phagy, and potently suppresses breast cancer progression in vivo.

Published
2022
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3. Metabolic adaption of cancer cells toward autophagy: Is there a role for ER-phagy?

Author

Debora Gentile, Marianna Esposito, and Paolo Grumati

Subjects
cancer, autophagy, ER-phagy, hypoxia, ER stress, UPR, Biology (General), QH301-705.5
Abstract

Autophagy is an evolutionary conserved catabolic pathway that uses a unique double-membrane vesicle, called autophagosome, to sequester cytosolic components, deliver them to lysosomes and recycle amino-acids. Essentially, autophagy acts as a cellular cleaning system that maintains metabolic balance under basal conditions and helps to ensure nutrient viability under stress conditions. It is also an important quality control mechanism that removes misfolded or aggregated proteins and mediates the turnover of damaged and obsolete organelles. In this regard, the idea that autophagy is a non-selective bulk process is outdated. It is now widely accepted that forms of selective autophagy are responsible for metabolic rewiring in response to cellular demand. Given its importance, autophagy plays an essential role during tumorigenesis as it sustains malignant cellular growth by acting as a coping-mechanisms for intracellular and environmental stress that occurs during malignant transformation. Cancer development is accompanied by the formation of a peculiar tumor microenvironment that is mainly characterized by hypoxia (oxygen < 2%) and low nutrient availability. Such conditions challenge cancer cells that must adapt their metabolism to survive. Here we review the regulation of autophagy and selective autophagy by hypoxia and the crosstalk with other stress response mechanisms, such as UPR. Finally, we discuss the emerging role of ER-phagy in sustaining cellular remodeling and quality control during stress conditions that drive tumorigenesis.

Published
2022
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4. Challenging Safety and Efficacy of Retinal Gene Therapies by Retinogenesis

Author

Elena Marrocco, Rosa Maritato, Salvatore Botta, Marianna Esposito, and Enrico Maria Surace

Subjects
gene therapy, adeno-associated virus (AAV), retinal degeneration, transcription, zinc finger, retinitis pigmentosa, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Gene-expression programs modulated by transcription factors (TFs) mediate key developmental events. Here, we show that the synthetic transcriptional repressor (TR; ZF6-DB), designed to treat Rhodopsin-mediated autosomal dominant retinitis pigmentosa (RHO-adRP), does not perturb murine retinal development, while maintaining its ability to block Rho expression transcriptionally. To express ZF6-DB into the developing retina, we pursued two approaches, (i) the retinal delivery (somatic expression) of ZF6-DB by Adeno-associated virus (AAV) vector (AAV-ZF6-DB) gene transfer during retinogenesis and (ii) the generation of a transgenic mouse (germ-line transmission, TR-ZF6-DB). Somatic and transgenic expression of ZF6-DB during retinogenesis does not affect retinal function of wild-type mice. The P347S mouse model of RHO-adRP, subretinally injected with AAV-ZF6-DB, or crossed with TR-ZF6-DB or shows retinal morphological and functional recovery. We propose the use of developmental transitions as an effective mode to challenge the safety of retinal gene therapies operating at genome, transcriptional, and transcript levels.

Published
2021
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5. Differential effects of rapamycin and retinoic acid on expansion, stability and suppressive qualities of human CD4+CD25+FOXP3+ T regulatory cell subpopulations

Author

Cristiano Scottà, Marianna Esposito, Henrieta Fazekasova, Giorgia Fanelli, Francis C. Edozie, Niwa Ali, Fang Xiao, Mark Peakman, Behdad Afzali, Pervinder Sagoo, Robert I. Lechler, and Giovanna Lombardi

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Adoptive transfer of ex vivo expanded CD4+CD25+FOXP3+ regulatory T cells is a successful therapy for autoimmune diseases and transplant rejection in experimental models. In man, equivalent manipulations in bone marrow transplant recipients appear safe, but questions regarding the stability of the transferred regulatory T cells during inflammation remain unresolved. In this study, protocols for the expansion of clinically useful numbers of functionally suppressive and stable human regulatory T cells were investigated. Regulatory T cells were expanded in vitro with rapamycin and/or all-trans retinoic acid and then characterized under inflammatory conditions in vitro and in vivo in a humanized mouse model of graft-versus-host disease. Addition of rapamycin to regulatory T-cell cultures confirms the generation of high numbers of suppressive regulatory T cells. Their stability was demonstrated in vitro and substantiated in vivo. In contrast, all-trans retinoic acid treatment generates regulatory T cells that retain the capacity to secrete IL-17. However, combined use of rapamycin and all-trans retinoic acid abolishes IL-17 production and confers a specific chemokine receptor homing profile upon regulatory T cells. The use of purified regulatory T-cell subpopulations provided direct evidence that rapamycin can confer an early selective advantage to CD45RA+ regulatory T cells, while all-trans retinoic acid favors CD45RA− regulatory T-cell subset. Expansion of regulatory T cells using rapamycin and all-trans retinoic acid drug combinations provides a new and refined approach for large-scale generation of functionally potent and phenotypically stable human regulatory T cells, rendering them safe for clinical use in settings associated with inflammation.

Published
2013
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6. Erector spine plane block as postoperative rescue analgesia in thoracic surgery

Author

Antonio Corcione, Dino Casazza, Dario Maria Mattiacci, Marco Rispoli, Domenico Pietro Santonastaso, Moana Rossella Nespoli, Dario Amore, Marianna Esposito, and Roberta Tamburri

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, medicine.drug_class, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, Block (telecommunications), medicine, Humans, Pain Management, Anesthetics, Local, Muscle, Skeletal, Ultrasonography, Interventional, Aged, Pain, Postoperative, Plane (geometry), business.industry, Local anesthetic, Nerve Block, General Medicine, Middle Aged, Thoracic Surgical Procedures, Spine, Oncology, Rescue analgesia, Cardiothoracic surgery, Regional anesthesia, Anesthesia, Female, Analgesia, business
Abstract

Objective: Erector spine plane block (ESPB) is a newly defined regional anesthesia technique performed by injection of local anesthetic beneath the erector spine muscle. We tested ESPB as a regional rescue analgesia bedside technique to be performed in the thoracic surgical ward, reporting a 7-patient case series. Methods: We report our experience in rescue analgesia after thoracic surgery. During the postoperative stay, numeric rating scale (NRS) score >3 and inability to perform physiotherapy or effective cough due to postoperative pain represented the criteria for proposing rescue analgesia with ESPB. NRS at rest and during movements was recorded; blood gas analysis and spirometry were performed to evaluate PaO2/FiO2 (P/F), forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV1) before ESPB execution. After performing the ESPB, static and dynamic NRS, P/F, and FVC and FEV1 were recorded at 40 minutes and 80 minutes. Results: NRS had a reduction at rest and in dynamic assessment. The P/F did not improve but spirometric measures improved. FVC had a relevant improvement only after 80 minutes; FEV1 was increased after 40 minutes. Conclusion: The use of ESPB as postoperative rescue analgesia can offer several advantages due to effective rescue analgesia and safety that makes it easy to perform in the thoracic surgical ward or in an outpatient clinic setting.

Published
2020

7. Evolution Over Time of Ventilatory Management and Outcome of Patients With Neurologic Disease

Author

Tejerina E. E., Pelosi P., Robba C., Penuelas O., Muriel A., Barrios D., Frutos-Vivar F., Raymondos K., Du B., Thille A. W., Rios F., Gonzalez M., Del-Sorbo L., Marin M. D. C., Valle Pinheiro B., Soares M. A., Nin N., Maggiore S. M., Bersten A., Amin P., Cakar N., Young Suh G., Abroug F., Jibaja M., Matamis D., Ali Zeggwagh A., Sutherasan Y., Anzueto A., Esteban A, Fernando Ríos, Damian Violi, Marisol Rodríguez-Goñi, Roger Lamoglie, Fernando Villarejo, Norberto Tiribelli, Santiago Ilutovich, Matías Brizuela, Mariana Monllau, Fernando Saldarini, Silvina Borello, Alberto Marino, Mauricio Vinzio, Karina Bonasegla, Julián Hernández, María Belén Yapur, María Eugenia González, Sebastián E Mare, Judith Sagardía, Marco Bezzi, Cecilia Pereyra, Julian Strati, Daniel Vargas, Claudia Diaz, Pablo Gómez, Marcelo Palavecino, Graciela Elizabeth, Aguilera García, M Eugenia, Luis Pablo Cardonnet, Lisandro Betttini, Hernán Nuñez, Lucas Vallejo, Fernando Fernández, Jorge Arroyo, Daniel Duarte, Gerardo Filippa, Cayetano Galetti, Hernan Nunia, Fernando Lambert, Elisa Estenssoro, Marina Busico, Javier Horacio Álvarez, Alejandro Raimondi, Gustavo Badariotti, Martín Lugaro, Fernando Lipovestky, Alan Javier Zazu, Hugo Capponcelli, Patricia Vogl, Cristina Orlandi, Alejandro Gómez, Gustavo Jannello, Alejandro Risso, Leticia Rapetti, Guillermo Chiappero, Juan Domingo Fernández, Rodrigo E Gómez-Paz, Marcos Juan Zec, Pascual Valdez, Jorgelina Guyon, Ariel Chena, Sergio Lasdica, Martin Deheza, Schimdt Alejandra, Francisco Criado, Norma Beatriz Márquez, Pablo Desmery, José Luis Scapellato, Gonzalo Javier Ríos, Cristian Casabella, Jasmin Board, Andrew Davies, Andrew Bersten, Elisha Matheson, Amy Waters, John Santamaria, Jennifer Holmes, Cartan Costello, Manoj K Saxena, John Myburgh, Ellen Kinkel, Forbes McGain, Claire Cattigan, Allison Bone, Ian Seppelt, Leonie Weisbrodt, Cheryl Cuzner, Christopher MacIsaac, Deborah Barge, Tania Caf, Cameron Knott, Graeme Duke, Imogen Mitchell, Helen Rodgers, Rachel Whyte, Elisha Fulton, Alistair Nichol, Hergen Buscher, Priya Nair, Claire Reynolds, Simon J G Hockley, Ian Moore, Katherine Davidson, David Milliss, Raju Pusapati, Helen Wong, Jason Fletcher, Julie Smith, Paul Goldrick, Dianne Stephens, Jane Thomas, Anders Aneman, Sutrisno Gunawan, Tom Cowlam, George Lukas, Rick McAllister, Minka Springham, Joanne Sutton, Jeff Presneill, Tony Sutherland, Dianne Hill, Howard Connor, Jenny Dennett, Tim Coles, Freddy Sandy, Sando Chavarria, Marcelo Choque, Ronald Pairumani, Juan Guerra, Marco Antônio Soares Reis, José Carlos Versiani, Eduardo Fonseca Sad, Maria Aparecida Braga, Dinalva Aparecida Gomes, Fernando Antônio Botoni, Maurício Meireles Góes, Frederico Costa Val Barros, Rogério de Castro Pereira, Hugo Urbano, Valéria de Carvalho Magela, Aline Camile Yehia, Bruno Bonaccorsi Fernandino, Marco Antônio Ribeiro Leão, Rovílson Lara, Rubens Altair Amaral de Pádua, Janine Dias Alves, Aloísio Marques do Nascimento, Bruno do Valle Pinheiro, Carlos Alberto Studart Gomes, Marcelo Alcântara Holanda, Frederico Rodrigues Anselmo, Niall Ferguson, Neill Adhikari, Robert Fowler, Cheromi Sittambalam, Mehar-Un-Nisa Raja, Nicole Marinoff, Lauralyn McIntryre, Shawna Reddie, Laura Jones, Irene Watpool, Jeffrey Singh, Madison Dennis, Andrea Matte, Marc Lipkus, Ryan Albert, Andrew Steel, Emily Stern, Michael Miletin, Antonio Raso, Robyn Klages, Jan Friedrich, Orla Smith, Laura Wilson, Deborah Cook, Mark Bailey, Sangeeta Mehta, Stephen Lapinsky, Hannah Mathers, Cheryl Ethier, Stephanie Lubchansky, Samer Haj-Bakri, Dietrich Henzler, Lisa Julien, Luis Soto-Román, Juan Carlos Maurelia, César Antonio Maquilon, Luis Soto-Germani, Bin Du, Yan Kang, Bo Wang, Fachun Zhou, Fang Xu, Haibo Qiu, Yi Yang, Qingyuan Zhan, Bing Sun, Zhenjie Hu, Bin Yu, Xi Zhu, Yu Bai, Gang Li, Yi Li, Geng Zhang, Jianbiao Meng, Xiaobo Huang, Hong Pu, Daxing Yu, Chuanyun Qian, Wei Zhang, Yongjie Yin, Debiao Song, Yunxuan Yue, Zhengxuan Lv, Chengmin Yu, Qunmei Yao, Xue Wang, Yuan Xu, Wei He, Mian Chen, Zhihua Hu, Dongpo Jiang, Jian Huang, Wei Yu, Juanxian Gu, Yangong Chao, Zhixiang Li, Zhicheng Zhang, Wanxia Li, Zhenyang He, Jianguo Li, Chang Liu, Tiehe Qin, Shouhong Wang, Feng Li, Jun Jin, Jianhong Fu, Hongyang Xu, Hongyuan Lin, Jianying Guo, Yalin Liu, Jinghua Wang, Maoqin Li, Jiaqiong Li, Lei Chen, Qing Song, Liang Pan, Xianyao Wan, Jiuzhi Zhang, Weihai Yao, Yuhong Guo, Pang Wing Yan, Kelly Choy, Kwan Ming Chit, Patricia Leung, Chau Chin Man, Marco González, Ricardo Buitrago, Marcela Granados, Guillermo Ortiz, Cesar Enciso, Mario Gómez, Bladimir Alejandro Gil, Juan Pablo Sedano, Luis Fernando Castro Castro, Carlo Alberto Acosta, Marco Gonzalez, Francisco Molina, Camilo Pizarro, Mario Villabon, Carmelo Dueñas, Carlos Andrés Díaz, Nelson Fonseca, Rubén Camargo, Juan David Uribe, Hans-Henrik Bülow, Simona Beniczky, Jens Brushoj, Mikkel Præst, Birgitte Viebaek, Sine Wichman, Anette Mortensen, Susanne Andi Iversen, Bo Broberg, Edgard Luna, Manuel Jibaja, Leonardo Pazmiño, Katty Trelles, Fabricio Picoita, Gustavo Paredes, Vanesa Ramírez, Guillermo Falconí, Cristian Cevallos, Boris Villamagua, Marco Escobar, Freddy Sánchez, Miguel Llano, Miguel Lazcano, Ramiro Puetate, José Miguel Guerrero, Mijail Játiva, Myriam Montalvo, Franklin Villegas, Luis González Zambrano, Ronnie Mantilla, Gina Quinde, Andrea Gimenez, Luis Gonzalez Mosquera, Henry Caballero, María Fernanda García, Marcelo Ochoa, Soraya Puertas, Jackeline Coello, Mario Acosta, Medhat Soliman, Arnaud W Thille, Achille Kouatchet, Alain Mercat, Laurent Brochard, François Collet, Guillaume Marcotte, Pascal Beuret, Jean-Christophe M Richard, Gaëtan Bedunaeu, Pierre-Gildas Guitard, Fabien Soulis, Frédéric Bellec, Philippe Berger, Dorothée Carpentier, Benoit Veber, Salem Ould Zein, Géraldine Dessertaine, C Canevet, Fabien Grelon, Konstantinos Raymondos, Rolf Dembinski, Rolf Rossaint, Steffen Weber-Carstens, Christian Putensen, Maximillian Ragaller, Michael Quintel, Winfried Schubert, Thomas Bein, Heinrich Paulus, Walter Brandt, Lutz Pfeiffer, Silke Frenzel, Thoralf Kerner, P Kruska, Leila Eckholt, Joachim Hartung, Harald Fritz, Monika Holler, Johannes Busch, Andreas Viehöfer, Jens Buettner, Jörn Schlechtweg, Achim Lunkeit, Roland Schneider, Maria Wussow, Nils Marquardt, Christian Frenkel, Falk Hildebrandt, Tumbass Volker, Thomas Lipp, Cezar Mihailescu, Thomas Moellhoff, Thomas Steinke, Oliver Franke, Marcus Ruecker, Markus Schappacher, Steffen Appel, Heinz Kerger, Andreas Schwartz, Jan Dittmann, Jörg Haberkorn, Wolfgang Baier, Walter Seyde, Dimitros Matamis, Eleni Antoniadou, Pertsas Evangelos, Maria Giannakou, Zoltan Szentkereszty, Zsolt Molnar, Pravin Amin, Farhad N Kapadia, Nagarajan Ramakrishnan, Deepak Govil, Anitha Shenoy, Umesh G, Samir Sahu, Sheila Nainan Myatra, Subhash Kumar Todi, Sanjay Dhanuka, Mayur Patel, P Samaddar, Dhruva Chaudhry, Vivek Joshi, Srinivas Samavedam, Ankur Devendra Bhavsar, Prachee Sathe, Sujoy Mukherjee, Salvatore Maurizio Maggiore, Francesco Idone, Federica Antonicelli, Paolo Navalesi, Rosanna Vaschetto, Arianna Boggero, Rosalba Tufano, Michele Iannuzzi, Edoardo De Robertis, Romano Tetamo, Andrea Neville Cracchiolo, Antonio Braschi, Francesco Mojoli, Ilaria Curro', Mirko Belliato, Chiara Verga, Marta Ferrari, Erika Mannelli, Valerio Mangani, Giorgio Tulli, Francesca Frigieri, Armando Pedulla', Monica Rocco, Giorgia Citterio, Di Russo, Gaetano Perchiazzi, Loredana Pitagora, Antonio Pesenti, Michela Bombino, Davide Chiumello, Federica Tallarini, Serena Azzari, Antonina Pigna, Ivano Aprile, Marco Adversi, Antonio Corcione, Marianna Esposito, Annunziata Mattei, Vito Marco Ranieri, Rosario Urbino, Ilaria Maria Mastromauro, Antonino Giarratano, Maurizio Raineri Santi, Ambrogio Sansone, Younsuck Koh, Moo Suk Park, Je Hyeong Kim, Kyung Chan Kim, Hye Sook Choi, Yun Seong Kim, Jin Hwa Lee, Myung-Goo Lee, Won-Yeon Lee, Jin Young An, Gee Young Suh, Ki-Suck Jung, Asisclo J Villagómez Ortiz, César Cruz Lozano, Zalatiel Maycotte Luna, José Francisco López Baca, José Elizalde, Guillermo Cueto Robledo, Mario Alonso Treviño Salinas, Ricardo Martinez Zubieta, Claudia Olvera-Guzman, Marco Montes De Oca, Silvio A Ñamendys-Silva, José Salvador Martínez Cano, Jose Angel Baltazar Torres, Gustavo Morales Muñoz, Antonio Villa Delgado, Javier Ladape Martinez, Amine Ali Zeggwagh, Tarek Dendane, Abderrahim Azzouzi, Ahmed Sbihi, Wajdi Maazouzi, Mourad Amor, Charki Haimeur, Michael A Kuiper, Matty Koopmans, Uli Strauch, Dennis Bergmans, Serge Heines, Sylvia den Boer, Bas M Kors, Peter van der Voort, Paul J Dennesen, Bert Beishuizen, Ingrid van den Hul, Erna Alberts, Harry P P M Gelissen, Eduard Bootsma, Auke Reidinga, Kim Heus, Diane Mackle, Paul Young, Rachael Parke, Eileen Gilder, Jodi Brown, Lynette Newby, Catherine Simmonds, Jan Mehrtens, Seton Henderson, Tony Williams, Judi Tai, Chantal Hogan, Mary La Pine, John Durning, Sheree Gare, Troy Browne, Shirley Nelson, Jennifer Goodson, Julio Osorio, Chabu Coronado, Rollin Roldán Mori, Rosa Luz López Martínez, Adam Mikstacki, Barbara Tamowicz, Rui Moreno, Eduardo Almeida, Joana Silvestre, Heloisa Castro, Irene Aragão, Susana Alves Ferreira, Nelson Barros, Filomena Faria, Carlos André Correia Casado, Fausto Fialho Moura, Paulo Marcal, Ricardo Matos, Edward Nicolayenko, Mikhail Kirov, Andrey Yaroshetskiy, Andrei Piontek, Valery Subbotin, Yaseen Arabi, Olivia Dulfo, Chafrina Marie Olay, Edgardo E Tabhan, Nicolas Nin, Alfonso Muñoz, César Aragón, Ana Villagrá, Ainhoa Rosselló, Joan Maria Raurich, María Garitacelaya, Miguel Ángel González-Gallego, Francisco Ortuño, Miguel Fernández-Vivas, David Freire, Francisco Guerrero, Francisco Manzano, Juan Carlos, Alfredo Padrón, Pedro Rosa, Rafael Morales, Liliana Caipe, Maurizio Bottiroli, José María Nicolás, Marta Ugalde, Javier Ruiz, Lucia Capilla, Guillermo Muñiz, Jesús Sánchez-Ruiz, Javier Cebrián, Begoña Balerdi, Elena Parreño, Alvaro van Bommel, César Pérez-Calvo, Irene Dot, Javier Blanco, Raquel Manzanedo, José J Blanco, Daniel Fontaneda, Raúl González, Javier Díaz Domínguez, Alfonso Moreno, Antonio Reyes, Ian Carrasco, Itziar Mintegui, Rosa Sebastián, Javier García-Alonso, Carolina Lorencio, Josep Maria Sirvent, Patricia Jimeno, Miguel León, Pedro Galdos, Nuria Alonso, Julia López-Díaz, María Victoria de la Torre, Jorge Vidal Hernández, Nicolás Zamboschi, Francisco Lucena, Gemma Rialp, Raquel Montoiro, Victoria Goñi, María Ángeles Pena, Antonio Maestre, Marc Fabra, Jacinto Baena, Eva Benveniste, Susana Temprano, Jesús Sánchez, Carmen Campos, Sara Cabañes, María Elena Pérez-Losada, José Claudio Leo, Enrique Piacentini, María Del Carmen de la Torre, Laura Álvarez-Montero, Fernando Sánchez, Antonio Viñuales, Bernabé Álvarez, Javier Castañeda, Ángela Alonso, María Isabel Ruiz, Pedro Jesús Domínguez, Marcos Delgado, Eugenio Palazón, Antonio García-Jiménez, Rosa Álvaro, Clara Laplaza Eva Regidor, Enrique Maraví, José María Quiroga, Amalia Martínez de la Gandara, Cecilia Carbayo, María Luisa Navarrete, Manuel Valledor, Raquel Yano, José María Gutiérrez, Javier González-Robledo, Amparo Ferrandiz, Alberto Belenguer, Lidón Mateu, Laura Sayagues, María José Tolón, Nieves Franco, Elena Gallego, Félix Lacoma, Patricia Albert, Vicente Arraez, Mar Gobernado, Susana Moradillo, Carolina Gímenez-Esparza, Teresa Sánchez de Dios, Carlos Marian Crespo, Cecilia Hermosa, Federico Gordo, Genis Carrasco, María Ángeles Alonso, Alejandro Algora, Raúl de Pablo, Sofía García, Ana Carolina Caballero, José María Montón, Teresa Mut, Eva Manteiga, Alejandro de la Serna, Ana Esther Trujillo, Rafael Blancas, Inmaculada Vallverdú, José Manuel Serrano, Miquel Ferrer, Juan Diego Jiménez, Carlos Gallego, Dolores Vila, Luis Marina, Valentín Parra, Juan Ramón Cortés, Chen Chin-Ming, Ai-Chin Cheng, Fekri Abroug, Besbes Mohamed, Imed Chouchene, Mounir Bouaziz, Stambouli Neji, Islem Ouanes, Ayed Samia, Nahit Cakar, Ismail Kati, Ali Aydım Altunkan, Remzi Iscimen, Zafer Dogan, Bilge Çetin, Tayfun Adanir, Sabriye Guvenc, Unase Büyükkoçak, Antonio Anzueto, Ashley Ellis, Gary Kinasewitz, Allan Walkey, Phil Alkana, Gregory A Schmidt, Susan Gillen, Kathleen Lilli, Jennifer Twombley, Denice Wells, Larry Welder, Alejandro Arroliga, Alfredo Vasquez-Sandoval, Vincent John Scott, Craig Cernosek, Christopher Spradley, Dimple Tejwani, Sindhaghatta Venkatram, Gilda Diaz-Fuentes, Amber Monson, Anthony Saleh, Madhav Gudi, George Liziamma, Mohamed A Saad, Crissie De Spirito, Bryan Beatty, Samir Vermani, Crissie Despirito, Zaza Cohen, Amee Patrawalla, Samir Abdelhadi, Rupesh Vakil, Steven Y Chang, Brian Sherman, Rosanna Del Giudice, John Oropell, Timothy D Girard, Cayce Strength, Joyce Okahashi, Leanne Boehm, Matthew Kirchner, Erwin J Oei, Sebastian Circo, Nelson Medina, Mohammed Al-Jagbeer, V J Cardenas Jr, Smyth Smith, Shelby Sutton, Marcela Canola-Mazo, Tim Houlihan, Yogeet Kaur, Travis Parry, Craig A Piquette, Kerry Canady, Rahul Nanchal, Dana K Soetaert, Maria Del Mar Torres-Perez, Carlos Robles-Arias, William Rodriguez-Cintron, Mark Tidswell, Jennifer Germain, Lori-Ann Kozikowski, Erin Braden, Geneva Tatem, Javier Hurtado, Alberto Deicas, Daniel Weiss, Marta Beron, Román Garrido, Cristina Santos, Mario Cancela, Raúl Lombardi, Pedro Alzugaray, Jorge Gerez, Silvia Mareque, Graciela Franca, Oscar Cluzet, Edgardo Nuñez, Julio Pontet, Sergio Cáceres, Elias Caragna, Alberto Soler, Frank Torres, Gastón Pittini, Gabriel D Empaire, Stevens Salva, Fernando Pérez, Clara Pacheco, Zoraida Parra, Ingrid Von der Osten, Luis Williams, José Salinas, Do Danh Quynh, Pham Thi Van Anh, Nguyen Huu Hoang, Nghuyen Ba Tuan, RS: NUTRIM - R2 - Liver and digestive health, MUMC+: MA Arts Assistenten IC (9), Intensive Care, MUMC+: MA Medische Staf IC (9), Tejerina E.E., Pelosi P., Robba C., Penuelas O., Muriel A., Barrios D., Frutos-Vivar F., Raymondos K., Du B., Thille A.W., Rios F., Gonzalez M., Del-Sorbo L., Marin M.D.C., Valle Pinheiro B., Soares M.A., Nin N., Maggiore S.M., Bersten A., Amin P., Cakar N., Young Suh G., Abroug F., Jibaja M., Matamis D., Ali Zeggwagh A., Sutherasan Y., Anzueto A., Esteban A, and Fernando Ríos, Damian Violi, Marisol Rodríguez-Goñi, Roger Lamoglie, Fernando Villarejo, Norberto Tiribelli, Santiago Ilutovich, Matías Brizuela, Mariana Monllau, Fernando Saldarini, Silvina Borello, Alberto Marino, Norberto Tiribelli, Mauricio Vinzio, Karina Bonasegla, Julián Hernández, María Belén Yapur, María Eugenia González, Sebastián E Mare, Judith Sagardía, Marco Bezzi, Cecilia Pereyra, Julian Strati, Daniel Vargas, Claudia Diaz, Pablo Gómez, Marcelo Palavecino, Graciela Elizabeth, Aguilera García, M Eugenia, Luis Pablo Cardonnet, Lisandro Betttini, Hernán Nuñez, Lucas Vallejo, Fernando Fernández, Jorge Arroyo, Daniel Duarte, Gerardo Filippa, Cayetano Galetti, Hernan Nunia, Fernando Lambert, Elisa Estenssoro, Marina Busico, Fernando Villarejo, Javier Horacio Álvarez, Alejandro Raimondi, Gustavo Badariotti, Martín Lugaro, Fernando Lipovestky, Alan Javier Zazu, Hugo Capponcelli, Patricia Vogl, Cristina Orlandi, Alejandro Gómez, Gustavo Jannello, Alejandro Risso, Leticia Rapetti, Guillermo Chiappero, Juan Domingo Fernández, Rodrigo E Gómez-Paz, Marcos Juan Zec, Pascual Valdez, Jorgelina Guyon, Ariel Chena, Sergio Lasdica, Martin Deheza, Schimdt Alejandra, Francisco Criado, Norma Beatriz Márquez, Pablo Desmery, José Luis Scapellato, Gonzalo Javier Ríos, Cristian Casabella, Jasmin Board, Andrew Davies, Andrew Bersten, Elisha Matheson, Amy Waters, John Santamaria, Jennifer Holmes, Cartan Costello, Manoj K Saxena, John Myburgh, Ellen Kinkel, Forbes McGain, Claire Cattigan, Allison Bone, Ian Seppelt, Leonie Weisbrodt, Cheryl Cuzner, Christopher MacIsaac, Deborah Barge, Tania Caf, Cameron Knott, Graeme Duke, Imogen Mitchell, Helen Rodgers, Rachel Whyte, Elisha Fulton, Jasmin Board, Andrew Davies, Alistair Nichol, Hergen Buscher, Priya Nair, Claire Reynolds, Simon J G Hockley, Ian Moore, Katherine Davidson, David Milliss, Raju Pusapati, Helen Wong, Jason Fletcher, Julie Smith, Paul Goldrick, Dianne Stephens, Jane Thomas, Anders Aneman, Sutrisno Gunawan, Tom Cowlam, George Lukas, Rick McAllister, Minka Springham, Joanne Sutton, Jeff Presneill, Tony Sutherland, Dianne Hill, Howard Connor, Jenny Dennett, Tim Coles, Freddy Sandy, Sando Chavarria, Marcelo Choque, Ronald Pairumani, Juan Guerra, Marco Antônio Soares Reis, José Carlos Versiani, Eduardo Fonseca Sad, Maria Aparecida Braga, Dinalva Aparecida Gomes, Fernando Antônio Botoni, Maurício Meireles Góes, Frederico Costa Val Barros, Rogério de Castro Pereira, Hugo Urbano, Valéria de Carvalho Magela, Aline Camile Yehia, Bruno Bonaccorsi Fernandino, Marco Antônio Ribeiro Leão, Rovílson Lara, Rovílson Lara, Rubens Altair Amaral de Pádua, Janine Dias Alves, Aloísio Marques do Nascimento, Bruno do Valle Pinheiro, Carlos Alberto Studart Gomes, Marcelo Alcântara Holanda, Frederico Rodrigues Anselmo, Niall Ferguson, Neill Adhikari, Robert Fowler, Cheromi Sittambalam, Mehar-Un-Nisa Raja, Nicole Marinoff, Lauralyn McIntryre, Shawna Reddie, Laura Jones, Irene Watpool, Jeffrey Singh, Madison Dennis, Andrea Matte, Marc Lipkus, Ryan Albert, Andrew Steel, Emily Stern, Michael Miletin, Antonio Raso, Robyn Klages, Jan Friedrich, Orla Smith, Laura Wilson, Deborah Cook, Mark Bailey, Sangeeta Mehta, Stephen Lapinsky, Hannah Mathers, Cheryl Ethier, Stephanie Lubchansky, Samer Haj-Bakri, Dietrich Henzler, Lisa Julien, Luis Soto-Román, Juan Carlos Maurelia, César Antonio Maquilon, Luis Soto-Germani, Bin Du, Yan Kang, Bo Wang, Fachun Zhou, Fang Xu, Haibo Qiu, Yi Yang, Qingyuan Zhan, Bing Sun, Zhenjie Hu, Bin Yu, Xi Zhu, Yu Bai, Gang Li, Yi Li, Geng Zhang, Jianbiao Meng, Xiaobo Huang, Hong Pu, Bin Du, Daxing Yu, Chuanyun Qian, Wei Zhang, Yongjie Yin, Debiao Song, Yunxuan Yue, Zhengxuan Lv, Chengmin Yu, Qunmei Yao, Xue Wang, Yuan Xu, Wei He, Mian Chen, Zhihua Hu, Dongpo Jiang, Jian Huang, Wei Yu, Juanxian Gu, Yangong Chao, Zhixiang Li, Zhicheng Zhang, Wanxia Li, Zhenyang He, Jianguo Li, Chang Liu, Tiehe Qin, Shouhong Wang, Feng Li, Jun Jin, Jianhong Fu, Hongyang Xu, Hongyuan Lin, Jianying Guo, Yalin Liu, Jinghua Wang, Maoqin Li, Jiaqiong Li, Lei Chen, Qing Song, Liang Pan, Xianyao Wan, Jiuzhi Zhang, Weihai Yao, Yuhong Guo, Pang Wing Yan, Kelly Choy, Kwan Ming Chit, Patricia Leung, Chau Chin Man, Marco González, Ricardo Buitrago, Marcela Granados, Guillermo Ortiz, Cesar Enciso, Mario Gómez, Bladimir Alejandro Gil, Juan Pablo Sedano, Luis Fernando Castro Castro, Carlo Alberto Acosta, Marco Gonzalez, Francisco Molina, Camilo Pizarro, Mario Villabon, Carmelo Dueñas, Carlos Andrés Díaz, Nelson Fonseca, Rubén Camargo, Juan David Uribe, Hans-Henrik Bülow, Simona Beniczky, Jens Brushoj, Mikkel Præst, Birgitte Viebaek, Sine Wichman, Anette Mortensen, Susanne Andi Iversen, Bo Broberg, Edgard Luna, Manuel Jibaja, Leonardo Pazmiño, Katty Trelles, Fabricio Picoita, Gustavo Paredes, Vanesa Ramírez, Guillermo Falconí, Cristian Cevallos, Boris Villamagua, Marco Escobar, Freddy Sánchez, Miguel Llano, Miguel Lazcano, Ramiro Puetate, José Miguel Guerrero, Mijail Játiva, Myriam Montalvo, Franklin Villegas, Luis González Zambrano, Ronnie Mantilla, Gina Quinde, Andrea Gimenez, Luis Gonzalez Mosquera, Henry Caballero, María Fernanda García, Marcelo Ochoa, Soraya Puertas, Jackeline Coello, Mario Acosta, Medhat Soliman, Arnaud W Thille, Achille Kouatchet, Alain Mercat, Laurent Brochard, François Collet, Guillaume Marcotte, Pascal Beuret, Jean-Christophe M Richard, Gaëtan Bedunaeu, Pierre-Gildas Guitard, Fabien Soulis, Frédéric Bellec, Philippe Berger, Dorothée Carpentier, Benoit Veber, Salem Ould Zein, Géraldine Dessertaine, C Canevet, Fabien Grelon, Konstantinos Raymondos, Rolf Dembinski, Rolf Rossaint, Steffen Weber-Carstens, Christian Putensen, Maximillian Ragaller, Michael Quintel, Winfried Schubert, Thomas Bein, Heinrich Paulus, Walter Brandt, Lutz Pfeiffer, Silke Frenzel, Thoralf Kerner, P Kruska, Leila Eckholt, Joachim Hartung, Harald Fritz, Monika Holler, Johannes Busch, Andreas Viehöfer, Jens Buettner, Jörn Schlechtweg, Achim Lunkeit, Roland Schneider, Maria Wussow, Nils Marquardt, Christian Frenkel, Falk Hildebrandt, Tumbass Volker, Thomas Lipp, Cezar Mihailescu, Thomas Moellhoff, Thomas Steinke, Oliver Franke, Marcus Ruecker, Markus Schappacher, Steffen Appel, Heinz Kerger, Andreas Schwartz, Jan Dittmann, Jörg Haberkorn, Wolfgang Baier, Walter Seyde, Dimitros Matamis, Eleni Antoniadou, Pertsas Evangelos, Maria Giannakou, Zoltan Szentkereszty, Zsolt Molnar, Pravin Amin, Farhad N Kapadia, Nagarajan Ramakrishnan, Deepak Govil, Anitha Shenoy, Umesh G, Samir Sahu, Sheila Nainan Myatra, Subhash Kumar Todi, Sanjay Dhanuka, Mayur Patel, P Samaddar, Dhruva Chaudhry, Vivek Joshi, Srinivas Samavedam, Ankur Devendra Bhavsar, Prachee Sathe, Sujoy Mukherjee, Salvatore Maurizio Maggiore, Francesco Idone, Federica Antonicelli, Paolo Navalesi, Rosanna Vaschetto, Arianna Boggero, Rosalba Tufano, Michele Iannuzzi, Edoardo De Robertis, Romano Tetamo, Andrea Neville Cracchiolo, Antonio Braschi, Francesco Mojoli, Ilaria Curro', Mirko Belliato, Chiara Verga, Marta Ferrari, Erika Mannelli, Valerio Mangani, Giorgio Tulli, Francesca Frigieri, Armando Pedulla', Monica Rocco, Giorgia Citterio, Di Russo, Gaetano Perchiazzi, Loredana Pitagora, Antonio Pesenti, Michela Bombino, Davide Chiumello, Federica Tallarini, Serena Azzari, Antonina Pigna, Ivano Aprile, Marco Adversi, Antonio Corcione, Marianna Esposito, Annunziata Mattei, Vito Marco Ranieri, Rosario Urbino, Ilaria Maria Mastromauro, Antonino Giarratano, Maurizio Raineri Santi, Ambrogio Sansone, Younsuck Koh, Moo Suk Park, Je Hyeong Kim, Kyung Chan Kim, Hye Sook Choi, Yun Seong Kim, Jin Hwa Lee, Myung-Goo Lee, Won-Yeon Lee, Jin Young An, Gee Young Suh, Ki-Suck Jung, Asisclo J Villagómez Ortiz, César Cruz Lozano, Zalatiel Maycotte Luna, José Francisco López Baca, José Elizalde, Guillermo Cueto Robledo, Mario Alonso Treviño Salinas, Ricardo Martinez Zubieta, Claudia Olvera-Guzman, Marco Montes De Oca, Silvio A Ñamendys-Silva, José Salvador Martínez Cano, Jose Angel Baltazar Torres, Gustavo Morales Muñoz, Antonio Villa Delgado, Javier Ladape Martinez, Amine Ali Zeggwagh, Tarek Dendane, Abderrahim Azzouzi, Ahmed Sbihi, Wajdi Maazouzi, Mourad Amor, Charki Haimeur, Michael A Kuiper, Matty Koopmans, Uli Strauch, Dennis Bergmans, Serge Heines, Sylvia den Boer, Bas M Kors, Peter van der Voort, Paul J Dennesen, Bert Beishuizen, Ingrid van den Hul, Erna Alberts, Harry P P M Gelissen, Eduard Bootsma, Auke Reidinga, Jasmin Board, Andrew Davies, Kim Heus, Diane Mackle, Paul Young, Rachael Parke, Eileen Gilder, Jodi Brown, Lynette Newby, Catherine Simmonds, Jan Mehrtens, Seton Henderson, Tony Williams, Judi Tai, Chantal Hogan, Mary La Pine, John Durning, Sheree Gare, Troy Browne, Shirley Nelson, Jennifer Goodson, Julio Osorio, Chabu Coronado, Rollin Roldán Mori, Rosa Luz López Martínez, Adam Mikstacki, Barbara Tamowicz, Rui Moreno, Eduardo Almeida, Joana Silvestre, Heloisa Castro, Irene Aragão, Susana Alves Ferreira, Nelson Barros, Filomena Faria, Carlos André Correia Casado, Fausto Fialho Moura, Paulo Marcal, Ricardo Matos, Edward Nicolayenko, Mikhail Kirov, Andrey Yaroshetskiy, Andrei Piontek, Valery Subbotin, Yaseen Arabi, Olivia Dulfo, Chafrina Marie Olay, Edgardo E Tabhan, Nicolas Nin, Alfonso Muñoz, César Aragón, Ana Villagrá, Ainhoa Rosselló, Joan Maria Raurich, María Garitacelaya, Miguel Ángel González-Gallego, Francisco Ortuño, Miguel Fernández-Vivas, David Freire, Francisco Guerrero, Francisco Manzano, Juan Carlos, Alfredo Padrón, Pedro Rosa, Rafael Morales, Liliana Caipe, Maurizio Bottiroli, José María Nicolás, Marta Ugalde, Javier Ruiz, Lucia Capilla, Guillermo Muñiz, Jesús Sánchez-Ruiz, Javier Cebrián, Begoña Balerdi, Elena Parreño, Alvaro van Bommel, César Pérez-Calvo, Irene Dot, Javier Blanco, Raquel Manzanedo, José J Blanco, Daniel Fontaneda, Raúl González, Javier Díaz Domínguez, Alfonso Moreno, Antonio Reyes, Ian Carrasco, Itziar Mintegui, Rosa Sebastián, Javier García-Alonso, Carolina Lorencio, Josep Maria Sirvent, Patricia Jimeno, Miguel León, Pedro Galdos, Nuria Alonso, Julia López-Díaz, María Victoria de la Torre, Jorge Vidal Hernández, Nicolás Zamboschi, Francisco Lucena, Gemma Rialp, Raquel Montoiro, Victoria Goñi, María Ángeles Pena, Antonio Maestre, Marc Fabra, Jacinto Baena, Eva Benveniste, Susana Temprano, Jesús Sánchez, Carmen Campos, Sara Cabañes, María Elena Pérez-Losada, José Claudio Leo, Enrique Piacentini, María Del Carmen de la Torre, Laura Álvarez-Montero, Fernando Sánchez, Antonio Viñuales, Bernabé Álvarez, Javier Castañeda, Ángela Alonso, María Isabel Ruiz, Pedro Jesús Domínguez, Marcos Delgado, Eugenio Palazón, Antonio García-Jiménez, Rosa Álvaro, Clara Laplaza Eva Regidor, Enrique Maraví, José María Quiroga, Amalia Martínez de la Gandara, Cecilia Carbayo, María Luisa Navarrete, Manuel Valledor, Raquel Yano, José María Gutiérrez, Javier González-Robledo, Amparo Ferrandiz, Alberto Belenguer, Lidón Mateu, Laura Sayagues, María José Tolón, Nieves Franco, Elena Gallego, Félix Lacoma, Patricia Albert, Vicente Arraez, Mar Gobernado, Susana Moradillo, Carolina Gímenez-Esparza, Teresa Sánchez de Dios, Carlos Marian Crespo, Cecilia Hermosa, Federico Gordo, Genis Carrasco, María Ángeles Alonso, Alejandro Algora, Raúl de Pablo, Sofía García, Ana Carolina Caballero, José María Montón, Teresa Mut, Eva Manteiga, Alejandro de la Serna, Ana Esther Trujillo, Rafael Blancas, Inmaculada Vallverdú, José Manuel Serrano, Miquel Ferrer, Juan Diego Jiménez, Carlos Gallego, Dolores Vila, Luis Marina, Valentín Parra, Juan Ramón Cortés, Chen Chin-Ming, Ai-Chin Cheng, Fekri Abroug, Besbes Mohamed, Imed Chouchene, Mounir Bouaziz, Stambouli Neji, Islem Ouanes, Ayed Samia, Nahit Cakar, Ismail Kati, Ali Aydım Altunkan, Remzi Iscimen, Zafer Dogan, Bilge Çetin, Tayfun Adanir, Sabriye Guvenc, Unase Büyükkoçak, Antonio Anzueto, Ashley Ellis, Gary Kinasewitz, Allan Walkey, Phil Alkana, Gregory A Schmidt, Susan Gillen, Kathleen Lilli, Jennifer Twombley, Denice Wells, Larry Welder, Alejandro Arroliga, Alfredo Vasquez-Sandoval, Vincent John Scott, Craig Cernosek, Christopher Spradley, Dimple Tejwani, Sindhaghatta Venkatram, Gilda Diaz-Fuentes, Amber Monson, Anthony Saleh, Madhav Gudi, George Liziamma, Mohamed A Saad, Crissie De Spirito, Bryan Beatty, Samir Vermani, Crissie Despirito, Zaza Cohen, Amee Patrawalla, Samir Abdelhadi, Rupesh Vakil, Steven Y Chang, Brian Sherman, Rosanna Del Giudice, John Oropell, Timothy D Girard, Cayce Strength, Joyce Okahashi, Leanne Boehm, Matthew Kirchner, Ashley Ellis, Gary Kinasewitz, Erwin J Oei, Sebastian Circo, Nelson Medina, Mohammed Al-Jagbeer, V J Cardenas Jr, Smyth Smith, Shelby Sutton, Marcela Canola-Mazo, Tim Houlihan, Yogeet Kaur, Travis Parry, Craig A Piquette, Kerry Canady, Rahul Nanchal, Dana K Soetaert, Maria Del Mar Torres-Perez, Carlos Robles-Arias, William Rodriguez-Cintron, Mark Tidswell, Jennifer Germain, Lori-Ann Kozikowski, Erin Braden, Geneva Tatem, Javier Hurtado, Alberto Deicas, Daniel Weiss, Marta Beron, Román Garrido, Cristina Santos, Mario Cancela, Raúl Lombardi, Pedro Alzugaray, Jorge Gerez, Silvia Mareque, Graciela Franca, Oscar Cluzet, Edgardo Nuñez, Julio Pontet, Sergio Cáceres, Elias Caragna, Alberto Soler, Frank Torres, Gastón Pittini, Gabriel D Empaire, Stevens Salva, Fernando Pérez, Clara Pacheco, Zoraida Parra, Ingrid Von der Osten, Luis Williams, José Salinas, Do Danh Quynh, Pham Thi Van Anh, Nguyen Huu Hoang, Nghuyen Ba Tuan

Subjects
Male, medicine.medical_treatment, pulmonary complications, RESPIRATORY-DISTRESS-SYNDROME, Critical Care and Intensive Care Medicine, CASE-FATALITY, 0302 clinical medicine, Risk Factors, Brain Injuries, Traumatic, Multicenter Studies as Topic, Hospital Mortality, Prospective Studies, Simplified Acute Physiology Score, Stroke, POPULATION, Age Factors, ANEURYSMAL SUBARACHNOID HEMORRHAGE, Middle Aged, Hemorrhagic Stroke, Intensive Care Units, Observational Studies as Topic, Anesthesia, Breathing, Female, medicine.symptom, Ventilator Weaning, Cohort study, Adult, TRAUMATIC BRAIN-INJURY, Pressure support ventilation, mechanical ventilation, prognosis factors, ACUTE LUNG INJURY, 03 medical and health sciences, medicine, Humans, Aged, Ischemic Stroke, Mechanical ventilation, Noninvasive Ventilation, business.industry, MORTALITY, neurologic patients, Organ dysfunction, 030208 emergency & critical care medicine, Length of Stay, medicine.disease, TRENDS, Respiration, Artificial, 030228 respiratory system, Etiology, NEUROCRITICAL CARE, Nervous System Diseases, Tracheotomy, business
Abstract

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease.

Published
2021

8. Role of FAM134 paralogues in endoplasmic reticulum remodeling, ER-phagy, and Collagen quality control

Author

Giorgia Di Lorenzo, Alessio Reggio, Carmine Cirillo, Elena Polishchuk, Adeela Hussain, Mariana Tellechea, Paolo Grumati, Alexandra Stolz, Marianna Esposito, Ivana Peluso, Antje K. Huebner, Christian A. Hübner, Viviana Buonomo, Carmine Settembre, Rayene Berkane, Ramachandra M. Bhaskara, Gerhard Hummer, Reggio, A., Buonomo, V., Berkane, R., Bhaskara, R. M., Tellechea, M., Peluso, I., Polishchuk, E., Di Lorenzo, G., Cirillo, C., Esposito, M., Hussain, A., Huebner, A. K., Hubner, C. A., Settembre, C., Hummer, G., Grumati, P., and Stolz, A.

Subjects
Proteomics, Quality Control, autophagy, ER-phagy, Cellular homeostasis, Endoplasmic Reticulum, Biochemistry, Article, 03 medical and health sciences, ddc:570, Genetics, ddc:610, Fragmentation (cell biology), Receptor, ER‐phagy, Molecular Biology, Membrane Protein, 030304 developmental biology, Organelles, 0303 health sciences, Chemistry, Endoplasmic reticulum, 030302 biochemistry & molecular biology, Autophagy, Membrane Proteins, Articles, FAM134, Cell biology, Cell culture, Unfolded protein response, ER stre, Autophagy & Cell Death, Collagen, ER stress, Flux (metabolism)
Abstract

Degradation of the endoplasmic reticulum (ER) via selective autophagy (ER‐phagy) is vital for cellular homeostasis. We identify FAM134A/RETREG2 and FAM134C/RETREG3 as ER‐phagy receptors, which predominantly exist in an inactive state under basal conditions. Upon autophagy induction and ER stress signal, they can induce significant ER fragmentation and subsequent lysosomal degradation. FAM134A, FAM134B/RETREG1, and FAM134C are essential for maintaining ER morphology in a LC3‐interacting region (LIR)‐dependent manner. Overexpression of any FAM134 paralogue has the capacity to significantly augment the general ER‐phagy flux upon starvation or ER‐stress. Global proteomic analysis of FAM134 overexpressing and knockout cell lines reveals several protein clusters that are distinctly regulated by each of the FAM134 paralogues as well as a cluster of commonly regulated ER‐resident proteins. Utilizing pro‐Collagen I, as a shared ER‐phagy substrate, we observe that FAM134A acts in a LIR‐independent manner and compensates for the loss of FAM134B and FAM134C, respectively. FAM134C instead is unable to compensate for the loss of its paralogues. Taken together, our data show that FAM134 paralogues contribute to common and unique ER‐phagy pathways., Selective degradation of the ER is essential to maintain ER homeostasis. This study characterizes FAM134A and FAM134C as ER‐phagy receptors involved in Collagen quality control and identifies protein clusters differentially regulated by FAM134 paralogues.

Published
2021

9. Humanity. Tra paradigmi perduti e nuove traiettorie (Volume II) : Tra paradigmi perduti e nuove traiettorie (Volume II)

Author

Stefania Achella, Francesco Paolo Adorno, Maurizio Cambi, Roberto Marchesini, Stefan Lorenz Sorgner, Gian Paolo Faella, Giuseppe Gembillo, Yvonne Huetter-Almerigi, Luigi Imperato, Alessio Lembo, Fiorenza Manzo, Maria Anna Noto, Renato Trombelli, Daniela Calabrò, Marianna Esposito, Francesco Saverio Festa, Lucia Iuzzolini, Rosalia Peluso, Luca Scafoglio, Mariarosaria Varone, Dario Giugliano, Anna Pia Ruoppo, Stefania Achella, Francesco Paolo Adorno, Maurizio Cambi, Roberto Marchesini, Stefan Lorenz Sorgner, Gian Paolo Faella, Giuseppe Gembillo, Yvonne Huetter-Almerigi, Luigi Imperato, Alessio Lembo, Fiorenza Manzo, Maria Anna Noto, Renato Trombelli, Daniela Calabrò, Marianna Esposito, Francesco Saverio Festa, Lucia Iuzzolini, Rosalia Peluso, Luca Scafoglio, Mariarosaria Varone, Dario Giugliano, and Anna Pia Ruoppo

Abstract

Umano, postumano, transumano, antropocene, animalità, relazione mente-corpo, intelligenza artificiale, diritti umani e inclusione, humanitas e umanesimo: queste le aree tematiche di indagine dei saggi che compongono il secondo dei due volumi di Humanity. L'analisi che ne de- riva fotografa un'umanità che – dalla modernità alla con- temporaneità – si trova in continuo transito tra paradigmi perduti e nuove traiettorie. Le attuali emergenze umanitarie, i frequenti disastri ambientali, le non più avveniristiche ibridazioni tra umano e tecnica impongono un costante e rinnovato ripensamento delle condizioni e dei limiti a cui è esposta la nostra esistenza. La riflessione filosofica ed etico-politica sull'umano si situa, oggi, in una complessa e articolata scena di mondo: qui essa incontra il versante dell'arte o, più in generale, dell'estetico. Proprio risalendo alle origini del moderno, si possono trarre spunti per un rilancio critico del progetto umano, di un nuovo umanesimo finalmente depurato da retaggi ideo- logici e ipoteche metafisiche.

Published
2023

10. Effectiveness of home-based preoperative pulmonary rehabilitation in COPD patients undergoing lung cancer resection

Author

Moana Rossella Nespoli, Alfonso Fiorelli, Maria Rosaria Gioia, Giovanni Natale, Antonio Cennamo, Davide Di Natale, Carlo Curcio, Marco Rispoli, Andrea Bianco, Marianna Esposito, Mario De Finis, Ilernando Meoli, Fabio Perrotta, Salvatore Buono, Sabrina Lavoretano, Antonio Corcione, Rosario Salvi, Rispoli, M., Salvi, R., Cennamo, A., Di Natale, D., Natale, G., Meoli, I., Gioia, M. R., Esposito, M., Nespoli, M. R., De Finis, M., Buono, S., Corcione, A., Lavoretano, S., Bianco, A., Fiorelli, A., Curcio, C., and Perrotta, F.

Subjects
Cancer Research, medicine.medical_specialty, Copd patients, medicine.medical_treatment, 030204 cardiovascular system & hematology, Chronic obstructive pulmonary disease, home-based, non-small cell lung cancer, pulmonary rehabilitation, Resection, 03 medical and health sciences, 0302 clinical medicine, medicine, Pulmonary rehabilitation, Lung cancer, Lung function, Rehabilitation, business.industry, General Medicine, medicine.disease, Home based, Surgery, 030228 respiratory system, Oncology, business
Abstract

Objective: To investigate the effectiveness of a home-based preoperative rehabilitation program for improving preoperative lung function and surgical outcome of patients with chronic obstructive pulmonary disease (COPD) undergoing lobectomy for cancer. Methods: This was a prospective, observational, single-center study including 59 patients with mild COPD who underwent lobectomy for lung cancer. All patients attended a home-based preoperative rehabilitation program including a minimum of 3 sessions each week for 4 weeks. Each session included aerobic and anaerobic exercises. Participants recorded the frequency and the duration of exercise performed in a diary. The primary end point was to evaluate changes in lung function including predicted postoperative (PPO) forced expiratory volume in 1 second (FEV1), 6-minute walking distance test (6MWD), PPO diffusing capacity for carbon monoxide (DLCO) %, and blood gas analysis values before and after the rehabilitation program. Postoperative pulmonary complications were recorded and multivariable analysis was used to identify independent prognostic factors (secondary end point). Results: All patients completed the 4-week rehabilitation program. Thirteen of 59 (22%) patients (Group A) performed 1% and 6MWD before and after rehabilitation showed a significant improvement only in Group B. No significant changes in PPO DLCO% or in blood gas analysis values were seen. Nine patients presented postoperative pulmonary complications, including atelectasis ( n = 6), pneumonia ( n = 1), respiratory failure ( n = 1), and pulmonary embolism ( n = 1). Group A presented higher number of postoperative pulmonary complications than Group B (6 vs 3; p = 0.0005). Multivariate analysis showed that the number of weekly rehabilitation sessions was the only independent predictive factor ( p = 0.001). Conclusions: Our simple and low-cost rehabilitation program could improve preoperative clinical function in patients with mild to moderate COPD undergoing lobectomy and reduce postoperative pulmonary complications. All patients should be motivated to complete at least 3 rehabilitation sessions per week in order to obtain significant clinical benefits. Our preliminary results should be confirmed by larger prospective studies.

Published
2020

12. Intraoperative Extracorporeal Carbon Dioxide Removal During Apneic Oxygenation with an EZ-Blocker in Tracheal Surgery

Author

Dario Maria Mattiacci, Salvatore Buono, Marco Rispoli, Moana Rossella Nespoli, Marianna Esposito, and Antonio Corcione

Subjects
Apnea, medicine.medical_treatment, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, 0302 clinical medicine, Monitoring, Intraoperative, Bronchoscopy, medicine, Humans, Intubation, 030212 general & internal medicine, business.industry, General Medicine, Oxygenation, Carbon Dioxide, Middle Aged, respiratory system, medicine.disease, Respiration, Artificial, Tracheal Stenosis, Respiratory acidosis, 030228 respiratory system, Anesthesia, Breathing, Female, medicine.symptom, business, Airway, Hypercapnia
Abstract

Tracheal surgery requires continued innovation to manage the anesthetic during an open airway phase. A common approach is apneic oxygenation with continuous oxygen flow, but the lack of effective ventilation causes hypercapnia, with respiratory acidosis. We used extracorporeal carbon dioxide removal for intraoperative decapneization during apneic oxygenation in a 64-year-old woman who was scheduled for tracheal surgery because of tracheal stenosis caused by long-term intubation. Our findings demonstrate that even after 40 minutes of total apnea, using an EZ-blocker for oxygenation and external decapneization, hemodynamic and gas exchange variables never demonstrated any dangerous alterations.

Published
2016

13. Tracheal Ring Fracture Secondary to Percutaneous Tracheostomy: Is Tracheal Flaccidity a Risk Factor?

Author

Jole Petruzzi, Anna d’Elia, Annarita Torino, Marianna Esposito, Alfonso Fiorelli, Mario Santini, Fausto Ferraro, Raffaele Marfella, Ferraro, Fausto, Marfella, R, Esposito, M, Petruzzi, J, Torino, A, D'Elia, A, Santini, Mario, and Fiorelli, Alfonso

Subjects
Male, medicine.medical_specialty, Percutaneous, Critical Care, medicine.medical_treatment, mechanical ventilation, Palpation, Flaccidity, law.invention, Tracheostomy, Risk Factors, law, Intensive care, Bronchoscopy, medicine, Humans, Intubation, intensive care, APACHE, Aged, Retrospective Studies, Tracheomalacia, Aged, 80 and over, Mechanical ventilation, medicine.diagnostic_test, business.industry, bronchoscopic surgical procedure, Middle Aged, respiratory system, medicine.disease, Respiration, Artificial, Intensive care unit, Surgery, Trachea, Anesthesiology and Pain Medicine, Anesthesia, Female, Cardiology and Cardiovascular Medicine, business
Abstract

Objective To evaluate the risk factors of tracheal ring fracture and whether previous tracheal ring flaccidity predisposes to it in consecutive, mechanically ventilated, intensive care unit patients undergoing different percutaneous dilatational tracheostomy procedures (Ciaglia Blue Rhino, PercuTwist, and Ciaglia BlueDolphin). Design Single-center retrospective study performed between November 2006 and July 2013. Setting Single-center university hospital. Participants Two hundred nineteen consecutive intensive care unit patients. Interventions Video bronchoscopic percutaneous dilatational tracheostomies using different techniques, including Ciaglia Blue Rhino, PercuTwist, and Ciaglia BlueDolphin, were performed consecutively. During the procedure, the tracheal wall response to the routine external palpation was evaluated endoscopically to find the interanular space. An abnormal change in the tracheal ring shape (fingerprint) with anterior airway wall collapse was diagnosed as tracheal flaccidity. Measurements and Main Results Tracheal ring fracture occurred in 21 patients (9.6%). The proportion of tracheal ruptures was 16 (76.2%) after PercuTwist, 3 (14.3%) after Ciaglia Blue Dolphin, and 2 (9.5%) after the Blue Rhino technique. Significant risk factors for tracheal rupture were PercuTwist procedure (p = 0.02), tracheal flaccidity (p = 0.0001), and a period of intubation before a percutaneous dilatational tracheostomy procedure>14 days (p = 0.01). Conclusions In addition to the PercuTwist technique and intubation>14 days before tracheostomy, tracheal flaccidity was a significant risk factor for tracheal ring fracture. In the presence of this finding, a less traumatic tracheostomy procedure should be applied.

Published
2015

14. Sufentanil Sublingual Tablet System for theManagement of Postoperative Pain afterVideo-Assisted Thoracic Surgery: APreliminary Clinical Experience

Author

Antonio Corcione, Alfonso Fiorelli, Salvatore Buono, Marianna Esposito, Mona Rossella Nespoli, Marco Rispoli, Rispoli, Marco, Fiorelli, Alfonso, Nespoli, Mona Rossella, Esposito, Marianna, Corcione, Antonio, and Buono, Salvatore

Subjects
Adult, Male, medicine.medical_specialty, Lung Neoplasms, Sufentanil, Postoperative pain, Administration, Sublingual, MEDLINE, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, Humans, Pain Management, Medicine, Aged, Pain, Postoperative, Sublingual Tablet, Thoracic Surgery, Video-Assisted, business.industry, Analgesia, Patient-Controlled, Middle Aged, Surgery, Analgesics, Opioid, Anesthesiology and Pain Medicine, Cardiothoracic surgery, Anesthesia, Female, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, medicine.drug
Published
2017

15. Democracy and neoliberalism : on the crisis of democratic legitimacy caused by neoliberal transformation

Author

MARIANNA ESPOSITO

Abstract

Time has run out for democratic sovereignty in the now bygone era of neoliberal governmentality and the time "bought" in the thirty year period after the Second World War with social Welfare State policies is the price we now have to pay in terms of public debt and distributional conflict in an irreversible crisis of representative democracy

Published
2014

16. IL-17– and IFN-γ–Secreting Foxp3+ T Cells Infiltrate the Target Tissue in Experimental Autoimmunity

Author

Livia Garzetti, Marianna Esposito, Alessandra Bergami, Luca Battistini, Roberto Furlan, Francesca Ruffini, Giovanna Borsellino, Gianvito Martino, Esposito, M, Ruffini, F, Bergami, A, Garzetti, L, Borsellino, G, Battistini, L, Martino, Gianvito, and Furlan, R.

Subjects
Encephalomyelitis, Autoimmune, Experimental, Immunology, Mice, Transgenic, chemical and pharmacologic phenomena, Biology, Lymphocyte Activation, T-Lymphocytes, Regulatory, TCIRG1, Interferon-gamma, Mice, Interleukin 21, Animals, Immunology and Allergy, Cytotoxic T cell, IL-2 receptor, Interleukin 3, Inflammation, ZAP70, Interleukin-17, FOXP3, Forkhead Transcription Factors, hemic and immune systems, T-Lymphocytes, Helper-Inducer, Natural killer T cell, Antigens, Differentiation, Female
Abstract

CD4+Foxp3+ regulatory T cells (Tregs) have been considered crucial in controlling immune system homeostasis, and their derangement is often associated to autoimmunity. Tregs identification is, however, difficult because most markers, including CD25 and Foxp3, are shared by recently activated T cells. We show in this paper that CD4+Foxp3+ T cells are generated in peripheral lymphoid organs on immunization and readily accumulate in the target organ of an autoimmune reaction, together with classical inflammatory cells, constituting up to 50% of infiltrating CD4+ T cells. Most CD4+Foxp3+ T cells are, however, CD25− and express proinflammatory cytokines such as IL-17 and IFN-γ, questioning their suppressive nature. Moreover, in vitro CD4+ T lymphocytes from naive and autoimmune mice, stimulated to differentiate into Th1, Th2, Th17, and induced Tregs, display early mixed expression of lineage-specific markers. These results clearly point to an unprecedented plasticity of naive CD4+ T cells, that integrating inflammatory signals may change their fate from the initial lineage commitment to a different functional phenotype.

Published
2010

17. Rapamycin inhibits relapsing experimental autoimmune encephalomyelitis by both effector and regulatory T cells modulation

Author

Nicola Gagliani, Gianvito Martino, Francesca Ruffini, Roberto Furlan, Manuela Battaglia, Matteo Bellone, Marianna Esposito, Esposito, M, Ruffini, F, Bellone, M, Gagliani, N, Battaglia, MARCO MARIA, Martino, Gianvito, and Furlan, R.

Subjects
Antigens, Differentiation, T-Lymphocyte, Encephalomyelitis, Autoimmune, Experimental, Encephalomyelitis, Immunology, chemical and pharmacologic phenomena, Biology, T-Lymphocytes, Regulatory, Interferon-gamma, Mice, Multiple Sclerosis, Relapsing-Remitting, Immune system, Antigen, Immune Tolerance, Secondary Prevention, medicine, Animals, Immunology and Allergy, IL-2 receptor, Myelin Proteolipid Protein, Sirolimus, Drug Administration Routes, Multiple sclerosis, Interleukin-17, Experimental autoimmune encephalomyelitis, FOXP3, hemic and immune systems, medicine.disease, Peptide Fragments, Disease Models, Animal, Phenotype, Treatment Outcome, Lymphatic system, Neurology, Antigens, Surface, Cancer research, Female, Neurology (clinical), Immunosuppressive Agents
Abstract

Rapamycin is an oral immunosuppressant drug previously reported to efficiently induce naturally occurring CD4(+)CD25(+)FoxP3(+) regulatory T ((n)T(reg)) cells re-establishing long-term immune self-tolerance in autoimmune diseases. We investigated the effect of rapamycin administration to SJL/j mice affected by PLP(139-151)-induced relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE). We found that oral or intraperitoneal treatment at the peak of disease or at the end of the first clinical attack, dramatically ameliorated the clinical course of RR-EAE. Treatment suspension resulted in early reappearance of disease. Clinical response was associated with reduced central nervous system demyelination and axonal loss. Rapamycin induced suppression of IFN-gamma, and IL-17 release from antigen-specific T cells in peripheral lymphoid organs. While CD4(+)FoxP3(+) cells were unaffected, we observed disappearance of CD4(+)CD45RB(high) effector T (T(eff)) cells and selective expansion of T(reg) cells bearing the CD4(+)CD45RB(low)FoxP3(+)CD25(+)CD103(+) extended phenotype. Finally, the dual action of rapamycin on both T(eff) and T(reg) cells resulted in modulation of their ratio that closely paralleled disease course. Our data show that rapamycin inhibits RR-EAE, provide evidence for the immunological mechanisms, and indicate this compound as a potential candidate for the treatment of multiple sclerosis.

Published
2010

18. Video-assisted lung lobectomy in cardiac transplant recipient: Dynamic monitoring of cardiac output and fluid responsiveness

Author

Dario Maria Mattiacci, Antonio Corcione, Marianna Esposito, Giuseppe Rossi, Salvatore Buono, Moana Rossella Nespoli, and Marco Rispoli

Subjects
Heart transplantation, Cardiac output, medicine.medical_specialty, Lung, business.industry, medicine.medical_treatment, Cardiomyopathy, Cancer, 030204 cardiovascular system & hematology, medicine.disease, Surgery, 03 medical and health sciences, Preload, 0302 clinical medicine, medicine.anatomical_structure, 030202 anesthesiology, Cardiothoracic surgery, medicine, Adenocarcinoma, business
Abstract

Introduction: Heart transplant recipients have a significantly higher risk of any “de novo” cancer due to immunosuppressive therapy and also they have an increasing risk of infections. Carcinoma of lung represents one of the five most common malignancies in these transplant populations. Patients’ comorbidities may request high invasive intraoperative monitoring, as well as neuraxial analgesia to avoid acute pain stress response, exposing patients to iatrogenic nosocomial infection. Case Report: Our patient was admitted to thoracic surgery ward for lung adenocarcinoma and video assisted lung lobectomy was planned. She received heart transplantation 15 years before due to idiopathic dilatative cardiomyopathy and she had chronic rejection six years after transplant treated with corticosteroid therapy. Conclusion: Anesthesia management can be difficult in cardiac transplant recipients due to a potentially impaired heart function and hypotension should be avoided due to preload dependence

Published
2016

19. The therapeutic effect of mesenchymal stem cell transplantation in experimental autoimmune encephalomyelitis is mediated by peripheral and central mechanisms

Author

Roberto Furlan, Antonio Uccelli, Simona Casazza, Maria Cristina Principato, Tiziana Vigo, Marianna Esposito, Sara Morando, and Giovanni Novi

Subjects
CD4-Positive T-Lymphocytes, Central Nervous System, Encephalomyelitis, Autoimmune, Experimental, Drug Administration Routes, Mesenchymal stem cell, Experimental autoimmune encephalomyelitis, Medicine (miscellaneous), Clinical uses of mesenchymal stem cells, Forkhead Transcription Factors, Mesenchymal Stem Cells, Review, Cell Biology, Biology, Mesenchymal Stem Cell Transplantation, medicine.disease, Biochemistry, Genetics and Molecular Biology (miscellaneous), Neural stem cell, Endothelial stem cell, Immunology, medicine, Animals, Molecular Medicine, Progenitor cell, Stem cell, Stem cell transplantation for articular cartilage repair
Abstract

Stem cells are currently seen as a treatment for tissue regeneration in neurological diseases such as multiple sclerosis, anticipating that they integrate and differentiate into neural cells. Mesenchymal stem cells (MSCs), a subset of adult progenitor cells, differentiate into cells of the mesodermal lineage but also, under certain experimental circumstances, into cells of the neuronal and glial lineage. Their clinical development, however, has been significantly boosted by the demonstration that MSCs display significant therapeutic plasticity mainly occurring through bystander mechanisms. These features have been exploited in the effective treatment of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis where the inhibition of the autoimmune response resulted in a significant amelioration of disease and decrease of demyelination, immune infiltrates and axonal loss. Surprisingly, these effects do not require MSCs to engraft in the central nervous system but depend on the cells' ability to inhibit pathogenic immune responses both in the periphery and inside the central nervous system and to release neuroprotective and pro-oligodendrogenic molecules favoring tissue repair. These results paved the road for the utilization of MSCs for the treatment of multiple sclerosis.

Published
2012

20. Humanity. Tra paradigmi perduti e nuove traiettorie (Volume II): Tra paradigmi perduti e nuove traiettorie (Volume II)

Author

Stefania Achella, Francesco Paolo Adorno, Maurizio Cambi, Roberto Marchesini, Stefan Lorenz Sorgner, Gian Paolo Faella, Giuseppe Gembillo, Yvonne Huetter-Almerigi, Luigi Imperato, Alessio Lembo, Fiorenza Manzo, Maria Anna Noto, Renato Trombelli, Daniela Calabrò, Marianna Esposito, Francesco Saverio, Daniela Calabrò, Dario Giugliano, Rosalia Peluso, Anna Pia Ruoppo, Luca Scafoglio

22. Immunogenicity and therapeutic efficacy of phage-displayed beta-amyloid epitopes

Author

Ilaria Luccarini, Valeria Cicatiello, Pasquale Barba, Marianna Esposito, Antonella Prisco, Diana De Falco, Anna Fiorentini, and Fiorella Casamenti

Subjects
medicine.medical_treatment, viruses, Immunology, Mice, Transgenic, Plaque, Amyloid, Active immunization, Alzheimer's Disease, Coliphages, Antibodies, Epitope, Epitopes, Mice, Alzheimer Disease, Peptide Library, In vivo, medicine, Animals, Molecular Biology, Amyloid beta-Peptides, biology, Immunogenicity, Immunotherapy, Virology, Peptide Fragments, In vitro, Titer, biology.protein, Antibody, Vaccine
Abstract

In vitro and in vivo studies indicate that Alzheimer's Disease (AD) could be prevented or treated by active immunization against self-peptide beta-amyloid. In this study, we compared the immunogenicity of different regions of beta-amyloid, displayed on filamentous phages. We established that a filamentous phage displaying epitope 2-6 (AEFRH) of beta-amyloid at the N-terminus of Major Capside Protein (phage fdAD(2-6)) is more immunogenic than a phage displaying epitope 1-7 (DAEFRHD) that differs only in flanking residues. Monthly injections of fdAD(2-6) trigger a robust anti-beta-amyloid antibody response, and afford a significant reduction of plaque pathology in a mouse model of AD, whereas the same treatment, performed with phage fdAD(1-7), induces a lower anti-beta-amyloid titer and does not protect from amyloid deposition. "Memory" anti-amyloid antibodies induced by a single prime-boost cycle with vaccine fdAD(2-6), that have a lower titer compared to antibodies induced by monthly restimulations, do not prevent plaque pathology. Our data show that optimization of epitope display is essential in vaccine design, and suggest that the titer of the anti-amyloid response is the crucial parameter to obtain therapeutic efficacy in vivo.

Published
2008
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23. IL4 gene delivery to the CNS recruits regulatory T cells and induces clinical recovery in mouse models of multiple sclerosis

Author

Elena Brambilla, Alessandra Bergami, Gianvito Martino, Marianna Esposito, Fulvio Mavilio, G. Comi, U Del Carro, Anna Stornaiuolo, Alessandra Recchia, Stefano Amadio, Roberto Furlan, A Cattalini, Stefano Pluchino, Erica Butti, Butti, E, Bergami, A, Recchia, A, Brambilla, E, Del Carro, U, Amadio, S, Cattalini, A, Esposito, M, Stornaiuolo, A, Comi, G, Pluchino, S, Mavilio, F, Martino, G, and Furlan, R

Subjects
Central Nervous System, Multiple Sclerosis, Regulatory T cell, Genetic enhancement, Animal Female Gene Therapy/*methods Genetic Vectors/administration & dosage Green Fluorescent Proteins/analysis/genetics Helper Viruses/genetics Humans Interleukin-4/analysis/*genetics/immunology Mice Mice, Genetic Vectors, Green Fluorescent Proteins, Regulatory/*immunology, CCL1, Gene delivery, Biology, T-Lymphocytes, Regulatory, Leukocyte Disease Models, Viral vector, Adenoviridae, Inbred C57BL Multiple Sclerosis/immunology/pathology/*therapy Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes, Mice, immune system diseases, Transduction, Genetic, Genetics, medicine, Animals, Humans, Molecular Biology, Reverse Transcriptase Polymerase Chain Reaction, Multiple sclerosis, Experimental autoimmune encephalomyelitis, FOXP3, hemic and immune systems, Genetic Therapy, medicine.disease, Adenoviridae/genetics Animals Central Nervous System/*immunology/pathology Chemokines/immunology Chemotaxis, Mice, Inbred C57BL, Chemotaxis, Leukocyte, Disease Models, Animal, medicine.anatomical_structure, Immunology, Molecular Medicine, Female, Interleukin-4, Chemokines, Helper Viruses
Abstract

Central nervous system (CNS) delivery of anti-inflammatory cytokines, such as interleukin 4 (IL4), holds promise as treatment for multiple sclerosis (MS). We have previously shown that short-term herpes simplex virus type 1-mediated IL4 gene therapy is able to inhibit experimental autoimmune encephalomyelitis (EAE), an animal model of MS, in mice and non-human primates. Here, we show that a single administration of an IL4-expressing helper-dependent adenoviral vector (HD-Ad) into the cerebrospinal fluid (CSF) circulation of immunocompetent mice allows persistent transduction of neuroepithelial cells and long-term (up to 5 months) CNS transgene expression without toxicity. Mice affected by chronic and relapsing EAE display clinical and neurophysiological recovery from the disease once injected with the IL4-expressing HD-Ad vector. The therapeutic effect is due to the ability of IL4 to increase, in inflamed CNS areas, chemokines (CCL1, CCL17 and CCL22) capable of recruiting regulatory T cells (CD4+CD69- CD25+Foxp3+) with suppressant functions. CSF delivery of HD-Ad vectors expressing anti-inflammatory molecules might represent a valuable therapeutic option for CNS inflammatory disorders.

Published
2008

26. Preoperative optimization with levosimendan in heart failure patient undergoing thoracic surgery

Author

Carlo Curcio, Marianna Esposito, Marco Rispoli, Moana Rossella Nespoli, Salvatore Buono, Dario Maria Mattiacci, and Antonio Corcione

Subjects
medicine.medical_specialty, Pleural effusion, Levosimendan, medicine.medical_treatment, Cardiomyopathy, Case Report, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, medicine, Heart failure patient, Preoperative optimization, Heart transplantation, business.industry, respiratory system, medicine.disease, respiratory tract diseases, Surgery, Thoracic surgery, Cardiothoracic surgery, Heart failure, Anesthesia, cardiovascular system, business, Pleural biopsy, medicine.drug
Abstract

Highlights • The use of levosimendan for perioperative optimization of patients undergoing cardiac surgery has been reported in several studies, however it has not been thouroughly evaluated in cardiac failure patients undergoing non cardiac surgery. • Preoperative levosimendan administration is safe and effective in cardiac failure patient undergoing thoracic surgery. • Prophylactic preoperative levosimendan treatment in heart failure patients merits further study., Introduction We present the case of a patient with dilatative cardiomyopathy waiting for heart transplantation with pleural effusion to be subjected to pleural biopsy, treated with preoperative infusion of levosimendan to improve heart performances. Presentation of case A 56-year-old man (BMI 22,49) with dilatative cardiomyopathy (EF 18%) presented right pleural effusion. The levosimendan treatment protocol consisted of 24 h continuous infusion (0,1 ug/kg/min), without bolus. The patient was under continuous hemodynamic monitoring prior, during and after levosimendan administration. The surgery for pleural biopsy was performed with uniportal Video Assisted Thoracoscopic approach (VATS). Discussion A significant increase of Cardiac Index (CI) and Stroke Volume Index (SVI) were observed at 4 h after infusion initiation and was sustained during the next 24 h after the end of infusion. Levosimendan administration was safe. Conclusion In this case the prophylactic preoperative levosimendan administration is safe and effective in cardiac failure patient undergoing thoracic surgery, but prophylactic preoperative levosimendan treatment in these patients merits further study.

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27. Challenging Safety and Efficacy of Retinal Gene Therapies by Retinogenesis

Author

Marianna Esposito, Rosa Maritato, Salvatore Botta, Elena Marrocco, Enrico Maria Surace, Marrocco, E., Maritato, R., Botta, S., Esposito, M., and Surace, E. M.

Subjects
Retinal degeneration, Male, Transcription Factor, Genetic enhancement, genetic processes, Gene Expression, chemistry.chemical_compound, Mice, 0302 clinical medicine, Biology (General), Spectroscopy, Genes, Dominant, 0303 health sciences, Zinc Fingers, General Medicine, Dependovirus, Dependoviru, gene therapy, 3. Good health, Computer Science Applications, Cell biology, Chemistry, medicine.anatomical_structure, Female, Genetic Vector, transcription, Human, Genetically modified mouse, Rhodopsin, QH301-705.5, Transgene, Genetic Vectors, adeno-associated virus (AAV), Mice, Transgenic, Biology, Catalysis, Article, Retina, Inorganic Chemistry, 03 medical and health sciences, retinitis pigmentosa, Retinitis pigmentosa, autosomal dominant, medicine, Animals, Humans, natural sciences, Physical and Theoretical Chemistry, QD1-999, Molecular Biology, Gene, 030304 developmental biology, zinc finger, Animal, fungi, Organic Chemistry, Retinal, Genetic Therapy, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, chemistry, retinal degeneration, Transcriptome, 030217 neurology & neurosurgery, Transcription Factors
Abstract

Gene-expression programs modulated by transcription factors (TFs) mediate key developmental events. Here, we show that the synthetic transcriptional repressor (TR, ZF6-DB), designed to treat Rhodopsin-mediated autosomal dominant retinitis pigmentosa (RHO-adRP), does not perturb murine retinal development, while maintaining its ability to block Rho expression transcriptionally. To express ZF6-DB into the developing retina, we pursued two approaches, (i) the retinal delivery (somatic expression) of ZF6-DB by Adeno-associated virus (AAV) vector (AAV-ZF6-DB) gene transfer during retinogenesis and (ii) the generation of a transgenic mouse (germ-line transmission, TR-ZF6-DB). Somatic and transgenic expression of ZF6-DB during retinogenesis does not affect retinal function of wild-type mice. The P347S mouse model of RHO-adRP, subretinally injected with AAV-ZF6-DB, or crossed with TR-ZF6-DB or shows retinal morphological and functional recovery. We propose the use of developmental transitions as an effective mode to challenge the safety of retinal gene therapies operating at genome, transcriptional, and transcript levels.

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