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90 results on '"Iglesias, S."'

2. Intracranial complications of sinogenic and otogenic infections in children: an ESPN survey on their occurrence in the pre-COVID and post-COVID era

Author

Massimi, L., Cinalli, G., Frassanito, P., Arcangeli, V., Auer, C., Baro, V., Bartoli, A., Bianchi, F., Dietvorst, S., Di Rocco, F., Gallo, P., Giordano, F., Hinojosa, J., Iglesias, S., Jecko, V., Kahilogullari, G., Knerlich-Lukoschus, F., Laera, R., Locatelli, D., Luglietto, D., Luzi, M., Messing-Jünger, M., Mura, R., Ragazzi, P., Riffaud, L., Roth, J., Sagarribay, A., Pinheiro, M. Santos, Spazzapan, P., Spennato, P., Syrmos, N., Talamonti, G., Valentini, L., Van Veelen, M. L., Zucchelli, M., and Tamburrini, G.

Published
2024
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10. Intracranial complications of sinogenic and otogenic infections in children:an ESPN survey on their occurrence in the pre-COVID and post-COVID era

Author

Massimi, L., Cinalli, G., Frassanito, P., Arcangeli, V., Auer, C., Baro, V., Bartoli, A., Bianchi, F., Dietvorst, S., Di Rocco, F., Gallo, P., Giordano, F., Hinojosa, J., Iglesias, S., Jecko, V., Kahilogullari, G., Knerlich-Lukoschus, F., Laera, R., Locatelli, D., Luglietto, D., Luzi, M., Messing-Jünger, M., Mura, R., Ragazzi, P., Riffaud, L., Roth, J., Sagarribay, A., Pinheiro, M. Santos, Spazzapan, P., Spennato, P., Syrmos, N., Talamonti, G., Valentini, L., Van Veelen, M. L., Zucchelli, M., Tamburrini, G., Massimi, L., Cinalli, G., Frassanito, P., Arcangeli, V., Auer, C., Baro, V., Bartoli, A., Bianchi, F., Dietvorst, S., Di Rocco, F., Gallo, P., Giordano, F., Hinojosa, J., Iglesias, S., Jecko, V., Kahilogullari, G., Knerlich-Lukoschus, F., Laera, R., Locatelli, D., Luglietto, D., Luzi, M., Messing-Jünger, M., Mura, R., Ragazzi, P., Riffaud, L., Roth, J., Sagarribay, A., Pinheiro, M. Santos, Spazzapan, P., Spennato, P., Syrmos, N., Talamonti, G., Valentini, L., Van Veelen, M. L., Zucchelli, M., and Tamburrini, G.

Abstract

Background: COVID-19 pandemic is thought to have changed the epidemiology of some pediatric neurosurgical disease: among them are the intracranial complications of sinusitis and otitis (ICSO). According to some studies on a limited number of cases, both streptococci-related sinusitis and ICSO would have increased immediately after the pandemic, although the reason is not clear yet (seasonal changes versus pandemic-related effects). The goal of the present survey of the European Society for Pediatric Neurosurgery (ESPN) was to collect a large number of cases from different European countries encompassing the pre-COVID (2017–2019), COVID (2020–2021), and post-COVID period (2022–June 2023) looking for possible epidemiological and/or clinical changes. Material and methods: An English language questionnaire was sent to ESPN members about year of the event, patient’s age and gender, presence of immune-deficit or other favoring risk factors, COVID infection, signs and symptoms at onset, site of primary infection, type of intracranial complication, identified germ, type and number of surgical operations, type and duration of medical treatment, clinical and radiological outcome, duration of the follow-up. Results: Two hundred fifty-four cases were collected by 30 centers coming from 14 different European countries. There was a statistically significant difference between the post-COVID period (129 children, 86 cases/year, 50.7% of the whole series) and the COVID (40 children, 20 cases/year, 15.7%) or the pre-COVID period (85 children, 28.3 cases/year, 33.5%). Other significant differences concerned the presence of predisposing factors/concurrent diseases (higher in the pre-COVID period) and previous COVID infection (higher in the post-COVID period). No relevant differences occurred as far as demographic, microbiological, clinical, radiological, outcome, morbidity, and mortality data were concerned. Paranasal sinuses

Published
2024

13. A Moderated Mediation Analysis between Burnout Components and Hair Cortisol

Author

Gonzalez D, Fortuna F, Ibar C, Jacobsen D, Jamardo J, Duarte E, Iglesias S, Gelos DS, Mesch V, Zopatti D, Berg G, Azzara S, and Fabre DB

Subjects
health services administration, health care facilities, manpower, and services, education, Ocean Engineering, psychological phenomena and processes
Abstract

In this research the relationship between hair cortisol and burnout was evaluated through the study of third-variables effect. Hair cortisol concentration was measured in 234 health workers. All participants completed perceived stress survey and Maslach Burnout Inventory. Our results showed that 40% of volunteers presented altered hair cortisol values, 12% burnout, 33% showed high depersonalization, 38% high emotional fatigue, 36% low personal fulfillment and 22% presented 2 of the 3 burnout components. A moderated mediation was found between psychological and biological variables. This research highlights the importance of including a biological variable such as hair cortisol in burnout assessment.

Published
2022
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15. Metal 3D printing for RF/microwave high-frequency parts

Author

Martín-Iglesias, P., Marechal, M., Calves, P., Hazard, M., Pambaguian, L., Brandao, A., Rodriguez Castillo, S., Martin, T., Percaz, J., Iza, V., Martín-Iglesias, S., Arregui, I., Teberio, F., Lopetegi, T., Laso, M. A. G., Martin, Thierry, Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Physique Théorique - UMR 7332 (CPT), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Université de Strasbourg (UNISTRA), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Logiques de l'Agir ( UR 2274) (LdA), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Strasbourg, Les Hôpitaux Universitaires de Strasbourg (HUS), Centre National d'Études Spatiales [Toulouse] (CNES), European Synchroton Radiation Facility [Grenoble] (ESRF), Nouvel Hôpital Civil de Strasbourg, CPT - E6 Nanophysique, Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Génie des Procédés et Matériaux (LGPM), CentraleSupélec-Université Paris-Saclay, Universidad Pública de Navarra. Departamento de Ingeniería Eléctrica, Electrónica y de Comunicación, and Nafarroako Unibertsitate Publikoa. Ingeniaritza Elektriko, Elektroniko eta Telekomunikazio Saila

Subjects
manufacturing, [SPI.ELEC]Engineering Sciences [physics]/Electromagnetism, microwave, e antennas, Space and Planetary Science, Waveguide, Aerospace Engineering, Antennas, space, 3D printing, waveguid
Abstract

Space Systems have been historically characterised by high performance, high reliability and high cost. Every new generation of space systems tends to improve performance, keep as much as possible reliability, speeding the lead time and lower the cost. Aggressive approach is nowadays followed by some of the players of the new space ecosystem where, for instance, reli- ability can be relaxed thanks for the in-orbit redundancy or robustness to failures by having a constellation with a high number of satellites. This push towards the technology and system limit requires to investigate new methods for the manufacturing of RF/Microwave parts. RF devices such as those based on waveguide structures, benefit from an additive manufacturing approach in terms of radio frequency (RF) performance and compactness. However each manufacturing approach comes with specific features and limitations which need to be well understood and, in some cases, even taking advantage of them. This paper provides a short review of some of the RF/Microwave parts already manufactured using this technology. The paper will focus mainly on metal 3D printing parts since this technology is, at the moment, well accepted by the space community. UPNA thanks the support of the Spanish Ministerio de Ciencia e Innovación-Agencia Estatal de Investigación (MCIN/AEI/ 10.13039/501100011033) under Project PID2020-112545RB-C53.

Published
2022
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17. A Moderated Mediation Analysis between Burnout Components and Hair Cortisol

Author

Gonzalez D, Fortuna F, Ibar C, Jacobsen D, Jamardo J Duarte E, Iglesias S, Gelos DS, Mesch V, Zopatti D, Berg G, Azzara S, Fabre DB

Subjects
health services administration, health care facilities, manpower, and services, education, Stress, Burnout, Mediation analysis, Hair cortisol, Health workers, psychological phenomena and processes
Abstract

In this research the relationship between hair cortisol and burnout was evaluated through the study of third-variables effect. Hair cortisol concentration was measured in 234 health workers. All participants completed perceived stress survey and Maslach Burnout Inventory. Our results showed that 40% of volunteers presented altered hair cortisol values, 12% burnout, 33% showed high depersonalization, 38% high emotional fatigue, 36% low personal fulfillment and 22% presented 2 of the 3 burnout components. A moderated mediation was found between psychological and biological variables. This research highlights the importance of including a biological variable such as hair cortisol in burnout assessment.

Published
2022

18. BMP-2 Enhances Osteogenic Differentiation of Human Adipose-Derived and Dental Pulp Stem Cells in 2D and 3D In Vitro Models

Author

Martin-Iglesias S, Milian L, Sancho-Tello M, Salvador-Clavell R, de Llano J, Carda C, and Mata M

Abstract

Bone tissue provides support and protection to different organs and tissues. Aging and different diseases can cause a decrease in the rate of bone regeneration or incomplete healing; thus, tissue-engineered substitutes can be an acceptable alternative to traditional therapies. In the present work, we have developed an in vitro osteogenic differentiation model based on mesenchymal stem cells (MSCs), to first analyse the influence of the culture media and the origin of the cells on the efficiency of this process and secondly to extrapolate it to a 3D environment to evaluate its possible application in bone regeneration therapies. Two osteogenic culture media were used (one commercial from Stemcell Technologies and a second supplemented with dexamethasone, ascorbic acid, glycerol-2-phosphate, and BMP-2), with human cells of a mesenchymal phenotype from two different origins: adipose tissue (hADSCs) and dental pulp (hDPSCs). The expression of osteogenic markers in 2D cultures was evaluated in several culture periods by means of the immunofluorescence technique and real-time gene expression analysis, taking as reference MG-63 cells of osteogenic origin. The same strategy was extrapolated to a 3D environment of polylactic acid (PLA), with a 3% alginate hydrogel. The expression of osteogenic markers was detected in both hADSCs and hDPSCs, cultured in either 2D or 3D environments. However, the osteogenic differentiation of MSCs was obtained based on the culture medium and the cell origin used, since higher osteogenic marker levels were found when hADSCs were cultured with medium supplemented with BMP-2. Furthermore, the 3D culture used was suitable for cell survival and osteogenic induction.

Published
2022

21. El bloqueo nervioso del plexo lumbar proporciona un mejor manejo analgésico que la infiltración periarticular en artroplastía total primaria de cadera. Ensayo clínico comparativo, prospectivo y simple ciego.

Author

Iglesias, S. L., Gentile, L., López, P., Pioli, I., Mangupli, M., Gómez, J., and Allende, B. L.

Abstract

Introduction: joint replacement is a highly effective intervention that significantly improves the patient's quality of life, relieves symptoms, restores joint function, and improves mobility and independence. The optimal pain control after total hip replacement has become an important goal of postoperative management. The purpose of this paper is to compare periarticular infiltration (PAI) and lumbar plexus nerve block (LPNB) for the management of post-operative pain in primary total hip arthroplasty because we believe that LPNB provides better analgesic management and lower opioid consumption. We evaluated the opioid usage during hospitalization and the complications derived from either technique. Material and methods: we randomized 45 patients who underwent elective total hip arthroplasty between January 2019 and January 2020. Two groups were evaluated based on the association of PAI or LPNB. Both as part of a multimodal analgesic regimen. Results: a total of 45 patients were evaluated (22 PAI group, 23 LPNB group). Block group required less opioid administration (p = 0.069). Most of the patients in both groups reported mild/moderate pain. The LPNB group had lower pain scale with physiotherapy. We did not have complications derived from either technique. Conclusion: lumbar plexus nerve block (LPNB) in patients undergoing total hip arthroplasty provides better pain management and reduced opioid consumption compared to PAI. The performance of this technique does not delay the beginning of physiotherapy and there were not any issues with the patient's recovery. [ABSTRACT FROM AUTHOR]

Published
2022
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22. Original[Artículo traducido] El bloqueo de nervios pericapsulares (PENG) es una alternativa efectiva y segura para el manejo del dolor postoperatorio después de una artroplastia total de cadera primaria: ensayo clínico aleatorizado

Author

Iglesias, S L, Nieto, I, López, P, Almada, A, Pioli, I, Astore, F, Urmenyi, C Rodríguez, and Allende, B L

Abstract

Introducción: El dolor postoperatorio luego de una artroplastia total de cadera puede afectar la rehabilitación postoperatoria y retrasar el alta hospitalaria. El objetivo de este estudio es comparar el bloqueo PENG con PAI, PNB para el manejo del dolor postoperatorio, la respuesta a la fisioterapia, el consumo de opioides y la duración de la estancia hospitalaria.

Published
2023
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23. Validation and utility of ARDS subphenotypes identified by machine-learning models using clinical data: an observational, multicohort, retrospective analysis

Author

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

Subjects
Pulmonary and Respiratory Medicine, Clinical Sciences, Acute Lung Injury, Article, Machine Learning, Positive-Pressure Respiration, Rare Diseases, Clinical Research, Retrospective Studie, Settore MED/41 - ANESTESIOLOGIA, Humans, Lung, Acute Respiratory Distress Syndrome, Retrospective Studies, Respiratory Distress Syndrome, Other Medical and Health Sciences, LUNG SAFE Investigators and the ESICM Trials Group, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Phenotype, Good Health and Well Being, Area Under Curve, ARDS: Phenotype, Respiratory, Public Health and Health Services, ARDS, Human
Abstract

Item does not contain fulltext BACKGROUND: Two acute respiratory distress syndrome (ARDS) subphenotypes (hyperinflammatory and hypoinflammatory) with distinct clinical and biological features and differential treatment responses have been identified using latent class analysis (LCA) in seven individual cohorts. To facilitate bedside identification of subphenotypes, clinical classifier models using readily available clinical variables have been described in four randomised controlled trials. We aimed to assess the performance of these models in observational cohorts of ARDS. METHODS: In this observational, multicohort, retrospective study, we validated two machine-learning clinical classifier models for assigning ARDS subphenotypes in two observational cohorts of patients with ARDS: Early Assessment of Renal and Lung Injury (EARLI; n=335) and Validating Acute Lung Injury Markers for Diagnosis (VALID; n=452), with LCA-derived subphenotypes as the gold standard. The primary model comprised only vital signs and laboratory variables, and the secondary model comprised all predictors in the primary model, with the addition of ventilatory variables and demographics. Model performance was assessed by calculating the area under the receiver operating characteristic curve (AUC) and calibration plots, and assigning subphenotypes using a probability cutoff value of 0·5 to determine sensitivity, specificity, and accuracy of the assignments. We also assessed the performance of the primary model in EARLI using data automatically extracted from an electronic health record (EHR; EHR-derived EARLI cohort). In Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE; n=2813), a multinational, observational ARDS cohort, we applied a custom classifier model (with fewer variables than the primary model) to determine the prognostic value of the subphenotypes and tested their interaction with the positive end-expiratory pressure (PEEP) strategy, with 90-day mortality as the dependent variable. FINDINGS: The primary clinical classifier model had an area under receiver operating characteristic curve (AUC) of 0·92 (95% CI 0·90-0·95) in EARLI and 0·88 (0·84-0·91) in VALID. Performance of the primary model was similar when using exclusively EHR-derived predictors compared with manually curated predictors (AUC=0·88 [95% CI 0·81-0·94] vs 0·92 [0·88-0·97]). In LUNG SAFE, 90-day mortality was higher in patients assigned the hyperinflammatory subphenotype than in those with the hypoinflammatory phenotype (414 [57%] of 725 vs 694 [33%] of 2088; p

Published
2022

24. Effectiveness of Non-Pharmacological Interventions in the Management of Pediatric Chronic Pain: A Systematic Review.

Author

Checa-Peñalver A, Lírio-Romero C, Luiz Ferreira EA, Hernandes-Iglesias S, García-Valdivieso I, Pérez-Pozuelo JM, and Gómez-Cantarino S

Abstract

(1) Background: Chronic pain in children remains an under-researched area, especially compared to acute pain. This systematic review aims to evaluate the effectiveness of non-pharmacological interventions in the management of pediatric chronic pain and their impact on the well-being of both children and their families. Given the growing interest in integrative treatments to reduce reliance on pharmacological solutions, this review addresses the need for alternative therapeutic approaches. (2) Methods: A systematic review was conducted following the PRISMA guidelines, covering studies published between 2019 and 2024 from PubMed, Cochrane Library, Web of Science, and Scopus. Eligible studies included children aged 2 to 18 years with chronic pain who received non-pharmacological interventions. Data were extracted on intervention types, participant characteristics, and outcomes. The risk of bias was assessed using RoB2 for randomized trials and ROBINS-I for non-randomized studies. (3) Results: A total of 11 studies involving 1739 children were included, assessing interventions such as cognitive behavioral therapy, personalized psychosocial follow-up programs, hypnotherapy, music therapy, and digital tools. The results demonstrated significant reductions in pain severity, improvements in emotional and physical well-being, and high patient satisfaction. However, the generalizability of findings was limited by the small sample sizes and variability in study designs. (4) Conclusions: Non-pharmacological interventions appear effective in managing pediatric chronic pain, offering improvements in pain reduction and quality of life. Further research is needed to optimize these approaches and confirm their long-term benefits across diverse populations. These interventions represent promising alternatives or complements to pharmacological treatments in pediatric pain management.

Published
2024
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25. Digital Doppelgängers and Lifespan Extension: What Matters?

Author

Iglesias S, Earp BD, Voinea C, Mann SP, Zahiu A, Jecker NS, and Savulescu J

Abstract

There is an ongoing debate about the ethics of research on lifespan extension: roughly, using medical technologies to extend biological human lives beyond the current "natural" limit of about 120 years. At the same time, there is an exploding interest in the use of artificial intelligence (AI) to create "digital twins" of persons, for example by fine-tuning large language models on data specific to particular individuals. In this paper, we consider whether digital twins (or digital doppelgängers, as we refer to them) could be a path toward a kind of life extension-or more precisely, a kind of person extension-that does not rely on biological continuity. We discuss relevant accounts of consciousness and personal identity and argue that digital doppelgängers may at least help us achieve some of the aims or ostensible goods of person-span extension, even if they may not count as literal extensions of our personhood on dominant philosophical accounts. We also consider relational accounts of personhood and discuss how digital doppelgängers may be able to extend personhood in a relational sense, or at least secure some of the goods associated with relevant relationships. We conclude by suggesting that a research program to investigate such issues is relevant to ongoing debates about the ethics of extending the human lifespan.

Published
2024
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26. A cohort analysis of familial partial lipodystrophy from two Mediterranean countries.

Author

Fernández-Pombo A, Yildirim Simsir I, Sánchez-Iglesias S, Ozen S, Castro AI, Atik T, Loidi L, Onay H, Prado-Moraña T, Adiyaman C, Díaz-López EJ, Altay C, Ginzo-Villamayor MJ, Akinci B, and Araújo-Vilar D

Subjects
Humans, Female, Male, Middle Aged, Adult, Spain epidemiology, Turkey epidemiology, Longitudinal Studies, Lamin Type A genetics, Cohort Studies, Hypertriglyceridemia complications, Hypertriglyceridemia epidemiology, Lipodystrophy, Familial Partial genetics, Lipodystrophy, Familial Partial epidemiology, Lipodystrophy, Familial Partial complications
Abstract

Aim: To assess the disease burden of familial partial lipodystrophy (FPLD) caused by LMNA (FPLD2) and PPARG (FPLD3) variants to augment the knowledge of these rare disorders characterized by selective fat loss and metabolic complications., Materials and Methods: An observational longitudinal study, including 157 patients (FPLD2: 139 patients, mean age 46 ± 17 years, 70% women; FPLD3: 18 patients, mean age: 44 ± 17 years, 78% women) from 66 independent families in two countries (83 from Turkey and 74 from Spain), was conducted., Results: Patients were diagnosed at a mean age of 39 ± 19 years, 20 ± 16 years after the first clinical signs appeared. Men reported symptoms later than women. Symptom onset was earlier in FPLD2. Fat loss was less prominent in FPLD3. In total, 92 subjects (59%) had diabetes (age at diagnosis: 34 ± 1 years). Retinopathy was more commonly detected in FPLD3 (P < .05). Severe hypertriglyceridaemia was more frequent among patients with FPLD3 (44% vs. 17%, P = .01). Hepatic steatosis was detected in 100 subjects (66%) (age at diagnosis: 36 ± 2 years). Coronary artery disease developed in 26 patients (17%) and 17 (11%) suffered from a myocardial infarction. Turkish patients had a lower body mass index, a higher prevalence of hepatic steatosis, greater triglyceride levels and a tendency towards a higher prevalence of coronary artery disease. A total of 17 patients died, with a mean time to death of 75 ± 3 years, which was shorter in the Turkish cohort (68 ± 2 vs. 83 ± 4 years, P = .01). Cardiovascular events were a major cause of death., Conclusions: Our analysis highlights severe organ complications in patients with FPLD, showing differences between genotypes and Mediterranean countries. FPLD3 presents a milder phenotype than FPLD2, but with comparable or even greater severity of metabolic disturbances., (© 2024 John Wiley & Sons Ltd.)

Published
2024
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27. [Internal validity and reliability of an instrument for evaluating quality of nursing care services for patients, nurses, and family members].

Author

Renghea A, Hernandez-Iglesias S, Cuevas-Budhart MA, Iglesias López MT, Sarrion-Bravo JA, Crespo Cañizares A, and Gómez Del Pulgar García-Madrid M

Subjects
Humans, Reproducibility of Results, Male, Female, Adult, Middle Aged, Quality of Health Care, Surveys and Questionnaires, Nursing Care standards, Factor Analysis, Statistical, Focus Groups, Psychometrics, Patient Satisfaction, Aged, Young Adult, Family
Abstract

Aim: To analyze the internal validity and reliability of the instrument for evaluating the quality of services adapted to three interest groups: patients, nurses, family members, and primary caregivers., Material and Method: Our research was conducted meticulously, employing a mixed methodology with two phases: qualitative, using the focus group for internal validation of the instrument, and quantitative. Subsequently, the survey was passed to the interest group of 430 patients, 525 relatives, and 298 nurses. Chronbac's alpha reliability analysis, the multiple linear regression model as a point estimator of the parameters, and exploratory factor analysis with a maximum likelihood factor using Kaiser-Meyer-Olkin to analyze the constructor and its indicators were performed to validate the adaptation. Finally, confirmatory factor analysis determines their respective measurement models' unidimensionality, validity, and reliability., Results: The result shows that the factor loading of each subconstruct is more significant than 0.5 in the three models, which indicates that the aptitude indices of the model were met. In addition, the model meets the discriminant validity criteria. The behavior of the SERVPERF questionnaire was analyzed in terms of consistency, Cronbach's alpha=0.94., Conclusion: The scale items' discrimination concerning the questions on global satisfaction is confirmed. This shows that the instrument is valid, reliable, and useful., (Copyright © 2024 FECA. Publicado por Elsevier España, S.L.U. All rights reserved.)

Published
2024
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28. A systematic review and meta-analysis focusing on the use of ayurvedic medicine in cerebral palsy.

Author

Rocha AMO, Len CA, Santos FH, Iglesias SBO, and Bissoto JR

Abstract

Integrative practices have been incorporated into palliative care to provide holistic and multidimensional care for patients. This study aims to identify the scope of integrative practices, specifically whole medical systems, and demonstrate its safety and efficacy, specially in children with cerebral palsy. Key databases, including Embase, Cochrane, Medline/PubMed, Scopus, Google Scholar, Lilacs and Scielo were searched using specific terms. Only randomized and non-randomized clinical trials were included for meta-analysis purposes. Case-control, cohort, cross-sectional or retrospective observational studies were also included for the systematic review. Participants included children aged 0-18 years receiving palliative care for cerebral palsy and undergoing Ayurvedic Medicine practices. Descriptive analysis was conducted, including data such as year; author; design; sample size; intervention and comparison; outcomes and conclusion. Two interventional studies compared Ayurvedic practices with each other or with physiotherapy in children with cerebral palsy. The meta-analysis demonstrated an improvement in spasticity for children using Ayurvedic medicine. However, there were limitations in terms of heterogeneity in interventions, control groups, and assessed outcomes. Integrative practices, including Ayurvedic medicine have the potential to improve quality of life, manage disease symptoms and provide emotional support. However, more robust evidence is needed to support their widespread use. The use of Ayurvedic medicine showed evidence of improvement in spasticity for children with cerebral palsy. REGISTRATION NUMBER: Prospero CRD 42020198399., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2024
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29. Lipodystrophic Laminopathies: From Dunnigan Disease to Progeroid Syndromes.

Author

Díaz-López EJ, Sánchez-Iglesias S, Castro AI, Cobelo-Gómez S, Prado-Moraña T, Araújo-Vilar D, and Fernandez-Pombo A

Subjects
Humans, Adipose Tissue metabolism, Adipose Tissue pathology, Phenotype, Mutation, Progeria genetics, Progeria pathology, Lamin Type A genetics, Lamin Type A metabolism, Lipodystrophy genetics, Lipodystrophy metabolism, Lipodystrophy pathology, Laminopathies genetics
Abstract

Lipodystrophic laminopathies are a group of ultra-rare disorders characterised by the presence of pathogenic variants in the same gene ( LMNA ) and other related genes, along with an impaired adipose tissue pattern and other features that are specific of each of these disorders. The most fascinating traits include their complex genotype-phenotype associations and clinical heterogeneity, ranging from Dunnigan disease, in which the most relevant feature is precisely adipose tissue dysfunction and lipodystrophy, to the other laminopathies affecting adipose tissue, which are also characterised by the presence of signs of premature ageing (Hutchinson Gilford-progeria syndrome, LMNA -atypical progeroid syndrome, mandibuloacral dysplasia types A and B, Nestor-Guillermo progeria syndrome, LMNA -associated cardiocutaneous progeria). This raises several questions when it comes to understanding how variants in the same gene can lead to similar adipose tissue disturbances and, at the same time, to such heterogeneous phenotypes and variable degrees of metabolic abnormalities. The present review aims to gather the molecular basis of adipose tissue impairment in lipodystrophic laminopathies, their main clinical aspects and recent therapeutic strategies. In addition, it also summarises the key aspects for their differential diagnosis.

Published
2024
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30. The surface charge of electroactive materials governs cell behaviour through its effect on protein deposition.

Author

Rodriguez-Lejarraga P, Martin-Iglesias S, Moneo-Corcuera A, Colom A, Redondo-Morata L, Giannotti MI, Petrenko V, Monleón-Guinot I, Mata M, Silvan U, and Lanceros-Mendez S

Subjects
Animals, Collagen Type I metabolism, Collagen Type I chemistry, Biocompatible Materials chemistry, Biocompatible Materials pharmacology, Cell Adhesion drug effects, Static Electricity, Fluorocarbon Polymers, Polyvinyls chemistry, Mesenchymal Stem Cells cytology, Mesenchymal Stem Cells metabolism, Mesenchymal Stem Cells drug effects, Surface Properties
Abstract

The precise mechanisms underlying the cellular response to static electric cues remain unclear, limiting the design and development of biomaterials that utilize this parameter to enhance specific biological behaviours. To gather information on this matter we have explored the interaction of collagen type-I, the most abundant mammalian extracellular protein, with poly(vinylidene fluoride) (PVDF), an electroactive polymer with great potential for tissue engineering applications. Our results reveal significant differences in collagen affinity, conformation, and interaction strength depending on the electric charge of the PVDF surface, which subsequently affects the behaviour of mesenchymal stem cells seeded on them. These findings highlight the importance of surface charge in the establishment of the material-protein interface and ultimately in the biological response to the material. STATEMENT OF SIGNIFICANCE: The development of new tissue engineering strategies relies heavily on the understanding of how biomaterials interact with biological tissues. Although several factors drive this process and their driving principles have been identified, the relevance and mechanism by which the surface potential influences cell behaviour is still unknown. In our study, we investigate the interaction between collagen, the most abundant component of the extracellular matrix, and poly(vinylidene fluoride) with varying surface charges. Our findings reveal substantial variations in the binding forces, structure and adhesion of collagen on the different surfaces, which collectively explain the differential cellular responses. By exposing these differences, our research fills a critical knowledge gap and paves the way for innovations in material design for advanced tissue regeneration strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Published
2024
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31. Lunar Lithium-7 Sensing ( δ 7Li): Spectral Patterns and Artificial Intelligence Techniques.

Author

Fernandez J, Fernandez S, Diez E, Pinilla-Alonso N, Pérez S, Iglesias S, Buendía A, Rodríguez J, and de Cos J

Abstract

Lithium, a critical natural resource integral to modern technology, has influenced diverse industries since its discovery in the 1950s. Of particular interest is lithium-7, the most prevalent lithium isotope on Earth, playing a vital role in applications such as batteries, metal alloys, medicine, and nuclear research. However, its extraction presents significant environmental and logistical challenges. This article explores the potential for lithium exploration on the Moon, driven by its value as a resource and the prospect of cost reduction due to the Moon's lower gravity, which holds promise for future space exploration endeavors. Additionally, the presence of lithium in the solar wind and its implications for material transport across celestial bodies are subjects of intrigue. Drawing from a limited dataset collected during the Apollo missions (Apollo 12, 15, 16, and 17) and leveraging artificial intelligence techniques and sample expansion through bootstrapping, this study develops predictive models for lithium-7 concentration based on spectral patterns. The study areas encompass the Aitken crater, Hadley Rima, and the Taurus-Littrow Valley, where higher lithium concentrations are observed in basaltic lunar regions. This research bridges lunar geology and the formation of the solar system, providing valuable insights into celestial resources and enhancing our understanding of space. The data used in this study were obtained from the imaging sensors (infrared, visible, and ultraviolet) of the Clementine satellite, which significantly contributed to the success of our research. Furthermore, the study addresses various aspects related to statistical analysis, sample quality validation, resampling, and bootstrapping. Supervised machine learning model training and validation, as well as data import and export, were explored. The analysis of data generated by the Clementine probe in the near-infrared (NIR) and ultraviolet-visible (UVVIS) spectra revealed evidence of the presence of lithium-7 (Li-7) on the lunar surface. The distribution of Li-7 on the lunar surface is non-uniform, with varying concentrations in different regions of the Moon identified, supporting the initial hypothesis associating surface Li-7 concentration with exposure to solar wind. While a direct numerical relationship between lunar topography and Li-7 concentration has not been established due to morphological diversity and methodological limitations, preliminary results suggest significant economic and technological potential in lunar lithium exploration and extraction.

Published
2024
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32. Cryo-EM analysis of Pseudomonas phage Pa193 structural components.

Author

Cingolani G, Iglesias S, Hou CF, Lemire S, Soriaga A, and Kyme P

Abstract

The World Health Organization has designated Pseudomonas aeruginosa as a critical pathogen for the development of new antimicrobials. Bacterial viruses, or bacteriophages, have been used in various clinical settings, commonly called phage therapy, to address this growing public health crisis. Here, we describe a high-resolution structural atlas of a therapeutic, contractile-tailed Pseudomonas phage, Pa193. We used bioinformatics, proteomics, and cryogenic electron microscopy single particle analysis to identify, annotate, and build atomic models for 21 distinct structural polypeptide chains forming the icosahedral capsid, neck, contractile tail, and baseplate. We identified a putative scaffolding protein stabilizing the interior of the capsid 5-fold vertex. We also visualized a large portion of Pa193 ~ 500 Å long tail fibers and resolved the interface between the baseplate and tail fibers. The work presented here provides a framework to support a better understanding of phages as biomedicines for phage therapy and inform engineering opportunities., Competing Interests: COMPETING INTERESTS STATEMENT J.R., E.S., R.G., A.S., L.S., P.K., D.B., and S.L. are employees of Armata Pharmaceuticals Inc., a company involved in the development of bacteriophage therapies. LG and JW were contracted by Armata under a fee-for-service agreement. The other authors declare that the research was conducted in a way that is free of financial or commercial relationship that could be construed as conflict of interest.

Published
2024
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33. Spinal cord lipomas: lessons learned in the era of total resection.

Author

Casado-Ruiz J, Ros B, Iglesias S, Ros A, and Arráez MA

Subjects
Child, Humans, Child, Preschool, Treatment Outcome, Neurosurgical Procedures methods, Retrospective Studies, Spinal Cord, Spinal Cord Neoplasms surgery, Lipoma surgery
Abstract

Purpose: Recent years have seen a paradigm shift towards total/near-total resection in spinal cord lipoma surgery. As this procedure is technically challenging, surgical candidates need to be selected appropriately through accurate image assessment and classification. The purpose of this paper is to describe a surgical series of paediatric spinal cord lipomas, their diagnosis, results and complications., Methods: We undertook a retrospective review of paediatric patients with spinal cord lipomas who underwent surgery between 2008 and 2022. The variables studied were age, gender, preoperative symptoms according to the Necker Functional Score (NFS), type of lipoma according to Morota's classification, functional and radiological surgical outcomes using the cord-sac ratio (CSR), need for re-operation, complications and follow-up., Results: A total of 25 patients (average age 36 months) underwent surgery. According to Morota's classification, MRI showed 13 type 1 lipomas, two type 2, two type 3 and eight type 4. The preoperative NFS was 16.06, with urological abnormalities being the most frequent manifestation. Total/near-total resection was attempted since 2015. Five patients with type 1 lipoma required re-operation due to clinical deterioration with suspected retethering, all of them with a CSR > 0.3. The series average CSR was 0.417., Conclusions: This paper highlights the importance of proper classification for a correct surgical approach to obtain favourable results and minimise possible complications. Based on our experience, given our results regarding the percentage of fistulae and retethering rates, we limited radical resection to symptomatic type 1 lipomas. Our future aim is to obtain better CSR rates and to decrease the retethering percentage., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2024
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34. Integrative structural analysis of Pseudomonas phage DEV reveals a genome ejection motor.

Author

Cingolani G, Lokareddy R, Hou CF, Forti F, Iglesias S, Li F, Pavlenok M, Niederweis M, and Briani F

Abstract

DEV is an obligatory lytic Pseudomonas phage of the N4-like genus, recently reclassified as Schitoviridae . The DEV genome encodes 91 ORFs, including a 3,398 amino acid virion-associated RNA polymerase. Here, we describe the complete architecture of DEV, determined using a combination of cryo-electron microscopy localized reconstruction, biochemical methods, and genetic knockouts. We built de novo structures of all capsid factors and tail components involved in host attachment. We demonstrate that DEV long tail fibers are essential for infection of Pseudomonas aeruginosa and dispensable for infecting mutants with a truncated lipopolysaccharide devoid of the O-antigen. We identified DEV ejection proteins and, unexpectedly, found that the giant DEV RNA polymerase, the hallmark of the Schitoviridae family, is an ejection protein. We propose that DEV ejection proteins form a genome ejection motor across the host cell envelope and that these structural principles are conserved in all Schitoviridae ., Competing Interests: COMPETING INTERESTS STATEMENT The authors declare no competing interests.

Published
2024
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35. Clinical Characteristics of Patients With Acquired Partial Lipodystrophy: A Multicenter Retrospective Study.

Author

Magno S, Ceccarini G, Corvillo F, Pelosini C, Gilio D, Paoli M, Fornaciari S, Pandolfo G, Sanchez-Iglesias S, Nozal P, Curcio M, Sessa MR, López-Trascasa M, Araújo-Vilar D, and Santini F

Subjects
Adult, Child, Female, Humans, Male, Retrospective Studies, Subcutaneous Fat pathology, Autoantibodies, Lipodystrophy diagnosis, Lipodystrophy epidemiology, Lipodystrophy genetics
Abstract

Background: Barraquer-Simons syndrome (BSS) is a rare, acquired form of lipodystrophy characterized by progressive loss of upper body subcutaneous fat, which affects face, upper limbs, and trunk. The pathogenesis of the disease is not entirely known and may involve autoimmune mechanisms., Aim: This study aimed to provide a comprehensive picture of the clinical, immunological, and metabolic features of a large cohort of patients with BSS. Our primary objectives included the validation of existing diagnostic tools, the evaluation of novel diagnostic approaches, and the exploration of potential disease triggers or genetic predispositions., Subjects and Methods: Twenty-six patients were diagnosed with BSS based on accepted criteria defined by international guidelines. Anthropometric parameters, biochemical tests, organ- and non-organ-specific autoantibodies, HLA status, and screening of the LMNB2 gene were performed., Results: Patients were predominantly females (73%); fat loss occurred mostly during childhood (77%) at a median age of 8 years. Among various anthropometric measures, the ratio between the proportion of fat mass in upper limbs and lower limbs showed the best predictive value for diagnosis. A total of 11.5% of patients had diabetes, 34.6% dyslipidemia, and 26.9% hepatic steatosis. Seventy-five percent of children and 50% of adults had C3 hypocomplementemia; 76% of patients were positive for 1 or more autoantibodies. HLA-DRB1 11:03 had higher allelic frequencies compared with the general population. A single variant in the LMNB2 gene was found in 1 patient., Conclusion: BSS has a childhood onset and is often associated with autoimmune diseases. Skinfold thickness measurements and fat assessment by dual energy X-ray absorptiometry are useful tools to identify the disease. C3 hypocomplementemia and the presence of autoantibodies may be used as additional diagnostic supportive criteria but the prevalence of C3 hypocomplementemia may be lower than previously reported., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2024
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36. Cancer Risks Associated With TP53 Pathogenic Variants: Maximum Likelihood Analysis of Extended Pedigrees for Diagnosis of First Cancers Beyond the Li-Fraumeni Syndrome Spectrum.

Author

Fortuno C, Feng BJ, Carroll C, Innella G, Kohlmann W, Lázaro C, Brunet J, Feliubadaló L, Iglesias S, Menéndez M, Teulé A, Ballinger ML, Thomas DM, Campbell A, Field M, Harris M, Kirk J, Pachter N, Poplawski N, Susman R, Tucker K, Wallis M, Williams R, Cops E, Goldgar D, James PA, and Spurdle AB

Subjects
Male, Female, Humans, United States, Middle Aged, Genes, p53 genetics, Pedigree, Tumor Suppressor Protein p53 genetics, Genetic Predisposition to Disease genetics, Risk Factors, Li-Fraumeni Syndrome diagnosis, Li-Fraumeni Syndrome genetics, Breast Neoplasms genetics
Abstract

Purpose: Establishing accurate age-related penetrance figures for the broad range of cancer types that occur in individuals harboring a pathogenic germline variant in the TP53 gene is essential to determine the most effective clinical management strategies. These figures also permit optimal use of cosegregation data for classification of TP53 variants of unknown significance. Penetrance estimation can easily be affected by bias from ascertainment criteria, an issue not commonly addressed by previous studies., Materials and Methods: We performed a maximum likelihood penetrance estimation using full pedigree data from a multicenter study of 146 TP53 -positive families, incorporating adjustment for the effect of ascertainment and population-specific background cancer risks. The analysis included pedigrees from Australia, Spain, and United States, with phenotypic information for 4,028 individuals., Results: Core Li-Fraumeni syndrome (LFS) cancers (breast cancer, adrenocortical carcinoma, brain cancer, osteosarcoma, and soft tissue sarcoma) had the highest hazard ratios of all cancers analyzed in this study. The analysis also detected a significantly increased lifetime risk for a range of cancers not previously formally associated with TP53 pathogenic variant status, including colorectal, gastric, lung, pancreatic, and ovarian cancers. The cumulative risk of any cancer type by age 50 years was 92.4% (95% CI, 82.2 to 98.3) for females and 59.7% (95% CI, 39.9 to 81.3) for males. Females had a 63.3% (95% CI, 35.6 to 90.1) cumulative risk of developing breast cancer by age 50 years., Conclusion: The results from maximum likelihood analysis confirm the known high lifetime risk for the core LFS-associated cancer types providing new risk estimates and indicate significantly increased lifetime risks for several additional cancer types. Accurate cancer risk estimates will help refine clinical recommendations for TP53 pathogenic variant carriers and improve TP53 variant classification.

Published
2024
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37. Effect of β-Estradiol on Adipogenesis in a 3T3-L1 Cell Model of Prelamin A Accumulation.

Author

Cobelo-Gómez S, Sánchez-Iglesias S, Fernández-Pombo A, and Araújo-Vilar D

Subjects
Humans, Female, Mice, Animals, Adipogenesis, 3T3-L1 Cells, Nuclear Proteins genetics, Estradiol pharmacology, Lipodystrophy, Familial Partial genetics, Lipodystrophy, Familial Partial metabolism, Lamin Type A
Abstract

The accumulation of farnesylated prelamin A has been suggested as one of the mechanisms responsible for the loss of fat in type 2 familial partial lipodystrophy due to variants in the LMNA gene. In this rare disease, fat loss appears in women after puberty, affecting sex-hormone-dependent anatomical areas. This study investigated the impact of 17-β-estradiol on adipogenesis in murine preadipocytes subjected to a pharmacologically induced accumulation of farnesylated and non-farnesylated prelamin A. To induce the accumulation of non-farnesylated or farnesylated prelamin A, 3T3-L1 cells were treated with the farnesyltransferase inhibitor 277 or the methyltransferase inhibitor N-acetyl-S-farnesyl-l-cysteine methylester. Subsequently, the cells were induced to undergo adipocyte differentiation in the presence or absence of 17-β-estradiol. Prelamin A accumulation was assessed through immunofluorescence, while real-time PCR and Western blot techniques were used to quantify several adipogenic genes and evaluate protein levels, respectively. The results showed that 17-β-estradiol increased adipogenesis, although the combination of this hormone plus farnesylated prelamin A led to a reduction in the number of mature adipocytes and the expression of the different genes involved in adipogenesis. In conclusion, the influence of farnesylated prelamin A accumulation on adipogenesis manifested only in the presence of estradiol. These in vitro findings suggest a potential mechanism that could explain the characteristic phenotype in women suffering type 2 familial partial lipodystrophy.

Published
2024
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38. Use of Localized Reconstruction to Visualize the Shigella Phage Sf6 Tail Apparatus.

Author

Hou CD, Li F, Iglesias S, and Cingolani G

Subjects
Virion, Research Design, Single Molecule Imaging, Siphoviridae, Shigella
Abstract

Cryogenic electron microscopy (cryo-EM) single-particle analysis has revolutionized the structural analysis of icosahedral viruses, including tailed bacteriophages. In recent years, localized (or focused) reconstruction has emerged as a powerful data analysis method to capture symmetry mismatches and resolve asymmetric features in icosahedral viruses. Here, we describe the methods used to reconstruct the 2.65-MDa tail apparatus of the Shigella phage Sf6, a representative member of the Podoviridae superfamily., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Published
2024
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39. Chitosan-based oral hydrogel formulations of β-galactosidase to improve enzyme supplementation therapy for lactose intolerance.

Author

Fraile-Gutiérrez I, Iglesias S, Acosta N, and Revuelta J

Subjects
Humans, Enzyme Stability, Hydrogels, Lactose metabolism, beta-Galactosidase metabolism, Hydrogen-Ion Concentration, Lactose Intolerance drug therapy, Chitosan
Abstract

β-Galactosidase supplementation plays an important role in the life of people with lactose intolerance. However, these formulations are rendered ineffective by the low pH and pepsin in the stomach and pancreatic proteases in the intestine. Therefore, it is necessary to develop oral transport systems for carrying this enzyme in the active form up to the intestine, where the lactose digestion occurs. In this research, a new hydrogel was developed that could potentially be used for enzyme supplement therapy. In this regard, the chitosan-based β-Gal formulations described in the manuscript are an alternative long-acting preparation to the so far available preparations that allow for enzyme protection and mucosal targeting. These hydrogels were prepared from chitosan and polyethylene glycol and contained a covalently immobilized β-galactosidase from Aspergillus oryzae. The β-galactosidase in the hydrogel was protected from degradation in a gastric medium at a pH of 2.5 and retained 75 % of its original activity under subsequent intestinal conditions. In the case of a simulated gastric fluid with a pH of 1.5, a copolymer containing methacrylic acid functional groups was sufficient to protect the hybrid hydrogel from the extremely acidic pH. In addition, the surface of the hydrogel was chemically modified with thiol and amidine groups, which increased the binding to intestinal mucin by 20 % compared with the unmodified hydrogel. These results represent a promising approach for oral transport as a reservoir for β-galactosidase in the small intestine to reduce the symptoms of hypolactasia., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Niuris Acosta and Julia Revuelta reports financial support was provided by Community of Madrid., (Copyright © 2023. Published by Elsevier B.V.)

Published
2024
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40. Clinical Characterisation and Comorbidities of Acquired Generalised Lipodystrophy: A 14-Year Follow-Up Study.

Author

Fernandez-Pombo A, Prado-Moraña T, Diaz-Lopez EJ, Sanchez-Iglesias S, Castro AI, Cobelo-Gomez S, and Araujo-Vilar D

Abstract

Acquired generalised lipodystrophy (AGL) is a rare disorder characterised by the gradual loss of fat that tends to generalise over time, the origin of which is still not fully clarified. The aim of this study was to offer a detailed description of seven patients with AGL (five women, 33.8 ± 18.6 years of age), evaluated over the last 14 years, in order to augment the knowledge of this disorder. The onset of the phenotype occurred during childhood and adolescence in five cases, and in adulthood in two cases. Three patients reported infections or vaccine administration prior to the development of lipodystrophy, and two subjects reported nodular swelling. The most frequent physical features were phlebomegaly, umbilical protrusion/hernia, and acanthosis nigricans. Skinfolds and body composition analysis showed the generalised absence of fat, with the exception of one patient in whom fat loss was spared in the trunk. The loss of fat in the palms/soles was observed in five subjects. Regarding metabolic comorbidities, throughout follow-up, two patients developed type 1 diabetes and one type 2 diabetes; three also presented hypertriglyceridaemia, one of whom developed acute pancreatitis, and no macrovascular complications were observed. Only one patient showed decreased complement C4. Autoimmunity was present in all cases, and six patients manifested Hashimoto's thyroiditis, type 1 diabetes, autoimmune hepatitis, and/or celiac disease. Thus, there are certain clinical characteristics of AGL that may be considered important diagnostic criteria to differentiate this disorder from other lipodystrophy subtypes.

Published
2023
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41. Natural history and comorbidities of generalised and partial lipodystrophy syndromes in Spain.

Author

Fernández-Pombo A, Sánchez-Iglesias S, Castro-Pais AI, Ginzo-Villamayor MJ, Cobelo-Gómez S, Prado-Moraña T, Díaz-López EJ, Casanueva FF, Loidi L, and Araújo-Vilar D

Subjects
Adolescent, Humans, Adult, Spain epidemiology, Prospective Studies, Syndrome, Lipodystrophy, Congenital Generalized diagnosis, Lipodystrophy, Congenital Generalized epidemiology, Lipodystrophy diagnosis, Lipodystrophy epidemiology, Lipodystrophy genetics
Abstract

The rarity of lipodystrophies implies that they are not well-known, leading to delays in diagnosis/misdiagnosis. The aim of this study was to assess the natural course and comorbidities of generalised and partial lipodystrophy in Spain to contribute to their understanding. Thus, a total of 140 patients were evaluated (77.1% with partial lipodystrophy and 22.9% with generalised lipodystrophy). Clinical data were collected in a longitudinal setting with a median follow-up of 4.7 (0.5-17.6) years. Anthropometry and body composition studies were carried out and analytical parameters were also recorded. The estimated prevalence of all lipodystrophies in Spain, excluding Köbberling syndrome, was 2.78 cases/million. The onset of phenotype occurred during childhood in generalised lipodystrophy and during adolescence-adulthood in partial lipodystrophy, with the delay in diagnosis being considerable for both cohorts. There are specific clinical findings that should be highlighted as useful features to take into account when making the differential diagnosis of these disorders. Patients with generalised lipodystrophy were found to develop their first metabolic abnormalities sooner and a different lipid profile has also been observed. Mean time to death was 83.8 ± 2.5 years, being shorter among patients with generalised lipodystrophy. These results provide an initial point of comparison for ongoing prospective studies such as the ECLip Registry study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fernández-Pombo, Sánchez-Iglesias, Castro-Pais, Ginzo-Villamayor, Cobelo-Gómez, Prado-Moraña, Díaz-López, Casanueva, Loidi and Araújo-Vilar.)

Published
2023
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42. A murine model of BSCL2-associated Celia's encephalopathy.

Author

Cobelo-Gómez S, Sánchez-Iglesias S, Rábano A, Senra A, Aguiar P, Gómez-Lado N, García-Varela L, Burgueño-García I, Lampón-Fernández L, Fernández-Pombo A, Díaz-López EJ, Prado-Moraña T, San Millán B, and Araújo-Vilar D

Abstract

Celia's encephalopathy or progressive encephalopathy with/without lipodystrophy is a neurodegenerative disease with a fatal prognosis in childhood. It is generally caused by the c.985C > T variant in the BSCL2 gene, leading to the skipping of exon 7 and resulting in an aberrant seipin protein (Celia-seipin). To precisely define the temporal evolution and the mechanisms involved in neurodegeneration, lipodystrophy and fatty liver in Celia's encephalopathy, our group has generated the first global knock-in murine model for the aberrant human transcript of BSCL2 (Bscl2 Celia/Celia ) using a strategy based on the Cre/loxP recombination system. In order to carry out a characterization at the neurological, adipose tissue and hepatic level, behavioral studies, brain PET, metabolic, histological and molecular studies were performed. Around 12% of homozygous and 5.4% of heterozygous knock-in mice showed severe neurological symptoms early in life, and their life expectancy was dramatically reduced. Severe generalized lipodystrophy and mild hepatic steatosis were present in these affected animals, while serum triglycerides and glucose metabolism were normal, with no insulin resistance. Furthermore, the study revealed a reduction in brain glucose uptake, along with patchy loss of Purkinje cells and the presence of intranuclear inclusions in cerebellar cortex cells. Homozygous, non-severely-affected knock-in mice showed a decrease in locomotor activity and greater anxiety compared with their wild type littermates. Bscl2 Celia/Celia is the first murine model of Celia's encephalopathy which partially recapitulates the phenotype and severe neurodegenerative picture suffered by these patients. This model will provide a helpful tool to investigate both the progressive encephalopathy with/without lipodystrophy and congenital generalized lipodystrophy., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2023
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43. Analysis of the impact of handling and culture on the expansion and functionality of NK cells.

Author

Martin-Iglesias S, Herrera L, Santos S, Vesga MÁ, Eguizabal C, Lanceros-Mendez S, and Silvan U

Subjects
Antibodies, Cell Membrane, Cell Separation, Cell- and Tissue-Based Therapy, Killer Cells, Natural, Receptors, Chimeric Antigen
Abstract

Natural killer (NK) cells are lymphocytes of the innate immune system that play a key role in the elimination of tumor and virus-infected cells. Unlike T cells, NK cell activation is governed by their direct interaction with target cells via the inhibitory and activating receptors present on their cytoplasmic membrane. The simplicity of this activation mechanism has allowed the development of immunotherapies based on the transduction of NK cells with CAR (chimeric antigen receptor) constructs for the treatment of cancer. Despite the advantages of CAR-NK therapy over CAR-T, including their inability to cause graft-versus-host disease in allogenic therapies, a deeper understanding of the impact of their handling is needed in order to increase their functionality and applicability. With that in mind, the present work critically examines the steps required for NK cell isolation, expansion and storage, and analyze the response of the NK cells to these manipulations. The results show that magnetic-assisted cell sorting, traditionally used for NK isolation, increases the CD16+ population of NK cultures only if the protocol includes both, antibody incubation and passage through the isolation column. Furthermore, based on the importance of surface potential on cellular responses, the influence of surfaces with different net surface charge on NK cells has been evaluated, showing that NK cells displayed higher proliferation rates on charged surfaces than on non-charged ones. The present work highlights the relevance of NK cells manipulation for improving the applicability and effectiveness of NK cell-based therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Martin-Iglesias, Herrera, Santos, Vesga, Eguizabal, Lanceros-Mendez and Silvan.)

Published
2023
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44. Role of psychological background in cancer susceptibility genetic testing distress: It is not only about a positive result.

Author

López-Fernández A, Villacampa G, Salinas M, Grau E, Darder E, Carrasco E, Solanes A, Velasco A, Torres M, Munté E, Iglesias S, Torres-Esquius S, Tuset N, Diez O, Lázaro C, Brunet J, Corbella S, and Balmaña J

Subjects
Humans, Female, Genetic Testing, Genetic Counseling psychology, Anxiety psychology, Stress, Psychological psychology, Neoplasms genetics
Abstract

Clinical and familial factors predict psychological distress after genetic testing for cancer susceptibility. However, the contribution of an individual's psychological background to such distress is unclear. This study aims to analyze the psychological impact of genetic testing and to identify the profile of individuals at higher risk. This is a longitudinal multicenter study of individuals undergoing genetic testing for cancer susceptibility. Demographic, clinical, genetic, familial, and psychological (personality types, cancer worry) characteristics were assessed by validated questionnaires the day of genetic testing. Distress, uncertainty, and positive experience perception (MICRA scale) were evaluated at the results disclosure visit, and 3 and 12 months afterwards. Multivariate analysis was performed. A total of 714 individuals were included. A high neuroticism score, high baseline cancer worry, and a positive genetic test result were independently associated with higher psychological impact (p-value < 0.05). The highest risk profile (10% of the cohort) included women with high level of neuroticism and a positive result. Uncertainty was mainly associated with a high level of neuroticism, regardless of the genetic test result. A holistic approach to personalized germline genetic counseling should include the assessment of personality dimensions., (© 2023 National Society of Genetic Counselors.)

Published
2023
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45. Liraglutide restores impaired associative learning in individuals with obesity.

Author

Hanssen R, Rigoux L, Kuzmanovic B, Iglesias S, Kretschmer AC, Schlamann M, Albus K, Edwin Thanarajah S, Sitnikow T, Melzer C, Cornely OA, Brüning JC, and Tittgemeyer M

Subjects
Male, Humans, Female, Glucagon-Like Peptide-1 Receptor, Glucagon-Like Peptide 1, Obesity drug therapy, Liraglutide pharmacology, Liraglutide therapeutic use, Insulin Resistance
Abstract

Survival under selective pressure is driven by the ability of our brain to use sensory information to our advantage to control physiological needs. To that end, neural circuits receive and integrate external environmental cues and internal metabolic signals to form learned sensory associations, consequently motivating and adapting our behaviour. The dopaminergic midbrain plays a crucial role in learning adaptive behaviour and is particularly sensitive to peripheral metabolic signals, including intestinal peptides, such as glucagon-like peptide 1 (GLP-1). In a single-blinded, randomized, controlled, crossover basic human functional magnetic resonance imaging study relying on a computational model of the adaptive learning process underlying behavioural responses, we show that adaptive learning is reduced when metabolic sensing is impaired in obesity, as indexed by reduced insulin sensitivity (participants: N = 30 with normal insulin sensitivity; N = 24 with impaired insulin sensitivity). Treatment with the GLP-1 receptor agonist liraglutide normalizes impaired learning of sensory associations in men and women with obesity. Collectively, our findings reveal that GLP-1 receptor activation modulates associative learning in people with obesity via its central effects within the mesoaccumbens pathway. These findings provide evidence for how metabolic signals can act as neuromodulators to adapt our behaviour to our body's internal state and how GLP-1 receptor agonists work in clinics., (© 2023. The Author(s).)

Published
2023
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46. Lung Ultrasound Abnormalities in Patients Without Pulmonary Pathology Prior to Surgery.

Author

Gonzalez Suarez S, Aznar de Legarra M, Barbara Ferreras A, Caicedo Toro M, Pelaez de la Fuente EM, Blazquez Martin J, Martin Iglesias S, and Monsalve Ortiz XE

Abstract

Background: The occurrence of lung ultrasound abnormalities in patients without lung disease remains uncertain, while patients with respiratory disease often exhibit such abnormalities., Objectives: The primary aim was to identify pathological ultrasonographic pulmonary findings and their correlation with baseline diseases and static lung compliance in patients without any pre-existing respiratory conditions., Methods: This prospective observational study enrolled a series of surgical patients with no history of pulmonary pathology (n = 104). Baseline diseases and patients' physical status classification, based on the American Society of Anesthesiologists (ASA), were documented by reviewing medical records. Prior to surgery, a lung ultrasound was performed to assess pulmonary changes. During surgery with general anesthesia, static lung compliance was measured. The Spearman correlation coefficient was employed to determine the correlation between the two variables., Results: Twenty-four patients (23.07%) exhibited 1 - 2 B-lines in certain lung fields. Seven patients (6.7%) had an ultrasound B-line score > 0 (indicating ≥ 3 B-lines). Among these patients, the average number of lung fields with ≥ 3 B-lines was 3.71 ± 2.43. Patients with systemic diseases (ASA ≥ 2) displayed a higher number of B-lines compared to ASA I patients (P-value = 0.039). Pleural irregularities were found in 10 patients (9.6%), while atelectasis and pleural effusion were observed in five (4.8%) and four (3.8%) patients, respectively. The mean lung compliance value was 56.78 ± 15.33. No correlation was observed between the total score of the B-lines and lung compliance (Spearman's correlation: rho = -0.028, P-value = 0.812)., Conclusions: Patients without pulmonary pathology may exhibit ultrasound pulmonary abnormalities, which tend to increase with higher ASA scores and do not appear to have a correlation with static lung compliance., Competing Interests: There are no conflicts of interest to declare., (Copyright © 2023, Gonzalez Suarez et al.)

Published
2023
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47. [Translated article] Pericapsular nerves block (PENG) is an effective and safe alternative for postoperative pain management after primary total hip arthroplasty: A randomised clinical trial.

Author

Iglesias SL, Nieto I, López P, Almada A, Pioli I, Astore F, Rodríguez Urmenyi C, and Allende BL

Abstract

Background: Postoperative pain after total hip arthroplasty can affect postoperative rehabilitation and delay hospital discharge. The objective of this study is to compare pericapsular nerves group (PENG) block with pericapsular infiltration (PAI) and plexus nerve block (PNB) for postoperative pain management, response to physical therapy, opioid consumption, and length of hospital stay after a primary total hip arthroplasty., Methods: Randomised clinical trial of parallel and blinded groups was performed. Sixty patients who underwent elective THA between December 2018 and July 2020 were randomised into the different groups (PENG, PAI and PNB). The visual analogue scale was used to assess pain; and motor function was measured with the Bromage scale. We also record opioid usage, length of hospital stay, and related medical complications., Results: Pain level at discharge was similar in all groups. Hospital stay was 1 day shorter in the PENG group (p<0.001) and they also had lower opioid consumption (p=0.044). Optimal motor recovery was similar in the groups (p=0.678). Pain control when performing physical therapy was better in the PENG group (p<0.0001)., Conclusions: PENG block is an effective and safe alternative for patients undergoing THA as it reduces opioid consumption and hospital stay compared to other analgesic methods., (Copyright © 2022 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.)

Published
2023
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48. Pericapsular nerves block (PENG) is an effective and safe alternative for postoperative pain management after primary total hip arthroplasty: A randomized clinical trial.

Author

Iglesias SL, Nieto I, López P, Almada A, Pioli I, Astore F, Rodríguez Urmenyi C, and Allende BL

Abstract

Background: Postoperative pain after total hip arthroplasty can affect postoperative rehabilitation and delay hospital discharge. The objective of this study is to compare pericapsular nerves group (PENG) block with pericapsular infiltration (PAI) and plexus nerve block (PNB) for postoperative pain management, response to physical therapy, opioid consumption, and length of hospital stay after a primary total hip arthroplasty., Methods: Randomized clinical trial of parallel and blinded groups was performed. Sixty patients who underwent elective THA between December 2018 and July 2020 were randomized into the different groups (PENG, PAI and PNB). The visual analog scale was used to assess pain; and motor function was measured with the Bromage scale. We also record opioid usage, length of hospital stay, and related medical complications., Results: Pain level at discharge was similar in all groups. Hospital stay was 1 day shorter in the PENG group (p<0.001) and they also had lower opioid consumption (p=0.044). Optimal motor recovery was similar in the groups (p=0.678). Pain control when performing physical therapy was better in the PENG group (p<0.0001)., Conclusions: PENG block is an effective and safe alternative for patients undergoing THA as it reduces opioid consumption and hospital stay compared to other analgesic methods., (Copyright © 2022 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.)

Published
2023
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49. Habitual daily intake of a sweet and fatty snack modulates reward processing in humans.

Author

Edwin Thanarajah S, DiFeliceantonio AG, Albus K, Kuzmanovic B, Rigoux L, Iglesias S, Hanßen R, Schlamann M, Cornely OA, Brüning JC, Tittgemeyer M, and Small DM

Subjects
Humans, Obesity metabolism, Weight Gain, Sugars, Snacks, Reward
Abstract

Western diets rich in fat and sugar promote excess calorie intake and weight gain; however, the underlying mechanisms are unclear. Despite a well-documented association between obesity and altered brain dopamine function, it remains elusive whether these alterations are (1) pre-existing, increasing the individual susceptibility to weight gain, (2) secondary to obesity, or (3) directly attributable to repeated exposure to western diet. To close this gap, we performed a randomized, controlled study (NCT05574660) with normal-weight participants exposed to a high-fat/high-sugar snack or a low-fat/low-sugar snack for 8 weeks in addition to their regular diet. The high-fat/high-sugar intervention decreased the preference for low-fat food while increasing brain response to food and associative learning independent of food cues or reward. These alterations were independent of changes in body weight and metabolic parameters, indicating a direct effect of high-fat, high-sugar foods on neurobehavioral adaptations that may increase the risk for overeating and weight gain., Competing Interests: Declaration of interests O.A.C. reports grants or contracts from Amplyx, Basilea, BMBF, Cidara, DZIF, EU-DG RTD (101037867), F2G, Gilead, Matinas, MedPace, MSD, Mundipharma, Octapharma, Pfizer, and Scynexis; consulting fees from Abbvie, Amplyx, Biocon, Biosys, Cidara, Da Volterra, Gilead, Matinas, MedPace, Menarini, Molecular Partners, MSG-ERC, Noxxon, Octapharma, Pardes, PSI, Scynexis, and Seres; honoraria for lectures from Abbott, Al-Jazeera Pharmaceuticals, Astellas, Grupo Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate, Merck/MSD, Mylan, and Pfizer; payment for expert testimony from Cidara; participation on a data safety monitoring board or advisory board for Actelion, Allecra, Cidara, Entasis, IQVIA, Janssen, MedPace, Paratek, PSI, Pulmocide, and Shionogi; a patent at the German Patent and Trade Mark Office (DE 10 2021 113 007.7)., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2023
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