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1. The role of patient-reported experiences in disclosing genetic prenatal testing: Findings from a large-scale survey on pregnant women

Author

Amerigo Ferrari, Federico Pennestrì, Manila Bonciani, Giuseppe Banfi, Milena Vainieri, and Rossella Tomaiuolo

Subjects
Prenatal testing, Value-based health care (VBHC), Patient-reported experience measures (PREMS), Non-invasive prenatal testing (NIPT), Survey, Gynecology and obstetrics, RG1-991
Abstract

Introduction: Pregnant women can choose from different prenatal genetic tests throughout their maternity journey. We aim to investigate the clinical, societal, and economic determinants influencing the selection of different options (non-invasive, invasive, or both). Methods: A systematic survey focusing on maternity pathways was launched by the Region of Tuscany, Italy, to collect data on pregnant women’s experience, outcomes and satisfaction levels. Drawing from this survey, we retrospectively analyzed data on women who filled out the second-trimester questionnaire between March 2019 and February 2023 (n = 27,337), providing complete data on relevant variables. Logistic regression models were applied to identify the factors contributing to a higher likelihood of opting for non-invasive prenatal testing (NIPT) and invasive testing. Results: Among the participants, 42.7 % chose only NIPT, 3.8 % opted for invasive tests exclusively, 1.3 % underwent both tests, and 52.2 % did not pursue any genetic testing. NIPT was more often chosen by older, Italian, highly educated, nulliparous women, who perceived better health, were employed (versus unemployed), had higher economic status, planned pregnancy, received hospital-based care (versus counseling center), under gynecologist supervision (versus midwife), not opted for combined testing and received pregnancy vaccinations. Conversely, invasive testing was more prevalent among older women but less common among those who were nulliparous, had Italian nationality, and had a perceived better health status. This group also tended to experience unplanned and high-risk pregnancy, did not take folate during pregnancy, received public hospital-based assistance, less frequently chose combined tests or NIPT, and had frequent delays in examinations. Conclusions: Various factors beyond clinical considerations influence the selection of a prenatal test. Therefore, NIPT pathways should include balanced, high-quality information about benefits and limitations, ensuring laboratory specialists' active and integrated involvement in decision-making.

Published
2024
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2. Long-term effectiveness of natalizumab in secondary progressive multiple sclerosis: A propensity-matched study

Author

Clara G. Chisari, Umberto Aguglia, Maria Pia Amato, Roberto Bergamaschi, Antonio Bertolotto, Simona Bonavita, Vincenzo Brescia Morra, Paola Cavalla, Eleonora Cocco, Antonella Conte, Salvatore Cottone, Giovanna De Luca, Alessia Di Sapio, Massimo Filippi, Antonio Gallo, Claudio Gasperini, Franco Granella, Giacomo Lus, Davide Maimone, Giorgia Teresa Maniscalco, Girolama Marfia, Lucia Moiola, Damiano Paolicelli, Ilaria Pesci, Paolo Ragonese, Marco Rovaris, Giuseppe Salemi, Claudio Solaro, Rocco Totaro, Maria Trojano, Marika Vianello, Mauro Zaffaroni, Vito Lepore, Francesco Patti, Carlo Avolio, Roberto Balgera, Paola Banfi, Paolo Bellantonio, Placido Bramanti, Lorenzo Capone, Guido Cavalletti, Luca Chiveri, Raffaella Clerici, Marinella Clerico, Francesco Corea, Vincenzo Dattola, Francesca De Robertis, Giancarlo Di Battista, Simonetta Galgani, Maurizia Gatto, Maria Grazia Grasso, Matilde Inglese, Lorenzo Lo Russo, Francesco Ottavio Logullo, Renato Mantegazza, Alessandra Protti, Monica Rezzonico, Mariarosa Rottoli, Marco Salvetti, Elio Scarpini, Leonardo Sinisi, Maddalena Sparaco, Daniele Spitaleri, Tiziana Tassinari, Simone Tonietti, Paola Valentino, Franco Valzania, and Simonetta Venturi

Subjects
Natalizumab, Interferon beta 1b, Secondary progressive multiple sclerosis, Disability progression, Neurology. Diseases of the nervous system, RC346-429
Abstract

Treatment options for secondary progressive MS (SPMS) are limited, especially considering that the new drugs recently approved are licensed for actively relapsing patients. We aimed to compare the disability progression in a real-world cohort of SPMS patients treated with natalizumab (NTZ) or interferon beta-1b (IFNb-1b). This multicenter retrospective enrolled patients with a diagnosis of SPMS according to 2014 Lublin criteria, who received NTZ or IFNb-1b for at least 48 months between the 1st June 2012 and the 15th May 2018 ​at 33 Italian MS centers contributing to the Italian MS Registry NTZ or IFNb-1b. Confirmed Expanded Disability Status Scale worsening (CEW) and progression independent of relapse (PIRA) were evaluated. In order to correct for non-randomization, a propensity score matching of the groups was performed. Out of 5206 MS patients identified at the time of data extraction, 421 SPMS patients treated with NTZ (224 [53.2%] females, mean age 45.3 ​± ​25.4 years) and 353 with IFNb-1b (133 [37.8%] females, mean age 48.5 ​± ​19.8 years) were enrolled. After applying the matching procedure, 102 patients were retained in the NTZ group and 98 in the IFNb-2b group. The proportion of patients who reached the 48-month 1-point CEW was significantly higher in IFNb-1b compared to NTZ group (58.2% versus 30.4%, p ​= ​0.01). The proportion of patients who developed PIRA at 48 months were significantly higher in IFNb-1b compared to NTZ (72.4% versus 40.2%, p ​= ​0.01). EDSS before treatment initiation and SPMS duration were risk factors for disability progression in terms of PIRA (HR 2.54, 25%CI 1.67–5.7; p ​= ​0.006 and HR 2.04, 25%CI 1.22–3.35; p ​= ​0.01, respectively). Patients treated with IFNb-1b were 1.64 times more to likely to develop PIRA (HR 1.64, 25%CI 1.04–4.87; p ​= ​0.001). Treatment with NTZ in SPMS patients showed more favorable disability outcomes compared to IFNb-1b with beneficial effects over 48 months.

Published
2024
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3. Whole genome sequencing identifies elusive variants in genetically unsolved Italian inherited retinal disease patients

Author

Roberta Zeuli, Marianthi Karali, Suzanne E. de Bruijn, Kim Rodenburg, Margherita Scarpato, Dalila Capasso, Galuh D.N. Astuti, Christian Gilissen, María Rodríguez-Hidalgo, Javier Ruiz-Ederra, Francesco Testa, Francesca Simonelli, Frans P.M. Cremers, Sandro Banfi, and Susanne Roosing

Subjects
WGS, inherited retinal diseases, IRD, unsolved monoallelic cases, deep intronic variants, DIVs, Genetics, QH426-470
Abstract

Summary: Inherited retinal diseases (IRDs) are a group of rare monogenic diseases with high genetic heterogeneity (pathogenic variants identified in over 280 causative genes). The genetic diagnostic rate for IRDs is around 60%, mainly thanks to the routine application of next-generation sequencing (NGS) approaches such as extensive gene panels or whole exome analyses. Whole-genome sequencing (WGS) has been reported to improve this diagnostic rate by revealing elusive variants, such as structural variants (SVs) and deep intronic variants (DIVs).We performed WGS on 33 unsolved cases with suspected autosomal recessive IRD, aiming to identify causative genetic variants in non-coding regions or to detect SVs that were unexplored in the initial screening. Most of the selected cases (30 of 33, 90.9%) carried monoallelic pathogenic variants in genes associated with their clinical presentation, hence we first analyzed the non-coding regions of these candidate genes. Whenever additional pathogenic variants were not identified with this approach, we extended the search for SVs and DIVs to all IRD-associated genes.Overall, we identified the missing causative variants in 11 patients (11 of 33, 33.3%). These included three DIVs in ABCA4, CEP290 and RPGRIP1; one non-canonical splice site (NCSS) variant in PROM1 and three SVs (large deletions) in EYS, PCDH15 and USH2A. For the previously unreported DIV in CEP290 and for the NCCS variant in PROM1, we confirmed the effect on splicing by reverse transcription (RT)-PCR on patient-derived RNA.This study demonstrates the power and clinical utility of WGS as an all-in-one test to identify disease-causing variants missed by standard NGS diagnostic methodologies.

Published
2024
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4. Rapid innervation and physiological epidermal regeneration by bioengineered dermis implanted in mouse

Author

Claudia Mazio, Isabella Mavaro, Antonio Palladino, Costantino Casale, Francesco Urciuolo, Andrea Banfi, Livia D'Angelo, Paolo A. Netti, Paolo de Girolamo, Giorgia Imparato, and Chiara Attanasio

Subjects
Human dermis equivalent, Endogenous ECM, In vivo skin defect model, Innervation, Vascularization, Epidermal appendages, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Tissue-engineered skin substitutes are promising tools to cover large and deep skin defects. However, the lack of a synergic and fast regeneration of the vascular network, nerves, and skin appendages limits complete skin healing and impairs functional recovery. It has been highlighted that an ideal skin substitute should mimic the structure of the native tissue to enhance clinical effectiveness. Here, we produced a pre-vascularized dermis (PVD) comprised of fibroblasts embedded in their own extracellular matrix (ECM) and a capillary-like network. Upon implantation in a mouse full-thickness skin defect model, we observed a very early innervation of the graft in 2 weeks. In addition, mouse capillaries and complete epithelialization were detectable as early as 1 week after implantation and, skin appendages developed in 2 weeks. These anatomical features underlie the interaction with the skin nerves, thus providing a further cue for reinnervation guidance. Further, the graft displays mechanical properties, collagen density, and assembly features very similar to the host tissue. Taken together our data show that the pre-existing ECM components of the PVD, physiologically organized and assembled similarly to the native tissue, support a rapid regeneration of dermal tissue. Therefore, our results suggest a promising potential for PVD in skin regeneration.

Published
2024
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5. Plasma Exosomes Refl Ect Myocardial Injury Detected by Cardiac Magnetic Resonance in STEMI Patients

Author

Andrea Baggiano, MD, Marta Zarà, PhD, Cristina Banfi, PhD, Jeness Campodonico, MD, Calogero Tedesco, PhD, Patrizia Amadio, PhD, Sebastiano Gili, MD, Gianluca De Dona, PhD, Leonardo Sandrini, PhD, Riccardo Maragna, MD, Daniele Junod, MD, Laura Fusini, MD, MSc, Saima Mushtaq, MD, Fabio Fazzari, MD, Giancarlo Marenzi, MD, Gianluca Pontone, MD, PhD, and Silvia Barbieri, PhD

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Published
2024
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6. A tetracationic porphyrin with dual anti-prion activity

Author

Antonio Masone, Chiara Zucchelli, Enrico Caruso, Giada Lavigna, Hasier Eraña, Gabriele Giachin, Laura Tapella, Liliana Comerio, Elena Restelli, Ilaria Raimondi, Saioa R. Elezgarai, Federica De Leo, Giacomo Quilici, Lorenzo Taiarol, Marvin Oldrati, Nuria L. Lorenzo, Sandra García-Martínez, Alfredo Cagnotto, Jacopo Lucchetti, Marco Gobbi, Ilaria Vanni, Romolo Nonno, Michele A. Di Bari, Mark D. Tully, Valentina Cecatiello, Giuseppe Ciossani, Sebastiano Pasqualato, Eelco Van Anken, Mario Salmona, Joaquín Castilla, Jesús R. Requena, Stefano Banfi, Giovanna Musco, and Roberto Chiesa

Subjects
Science
Published
2023
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7. Targeted sequencing and in vitro splice assays shed light on ABCA4-associated retinopathies missing heritability

Author

Zelia Corradi, Mubeen Khan, Rebekkah Hitti-Malin, Ketan Mishra, Laura Whelan, Stéphanie S. Cornelis, Carel B. Hoyng, Kati Kämpjärvi, Caroline C.W. Klaver, Petra Liskova, Heidi Stöhr, Bernhard H.F. Weber, Sandro Banfi, G. Jane Farrar, Dror Sharon, Jana Zernant, Rando Allikmets, Claire-Marie Dhaenens, and Frans P.M. Cremers

Subjects
ABCA4, ABCA4-associated retinopathies, missing heritability, smMIPs sequencing, deep-intronic variants, Genetics, QH426-470
Abstract

Summary: The ABCA4 gene is the most frequently mutated Mendelian retinopathy-associated gene. Biallelic variants lead to a variety of phenotypes, however, for thousands of cases the underlying variants remain unknown. Here, we aim to shed further light on the missing heritability of ABCA4-associated retinopathy by analyzing a large cohort of macular dystrophy probands. A total of 858 probands were collected from 26 centers, of whom 722 carried no or one pathogenic ABCA4 variant, while 136 cases carried two ABCA4 alleles, one of which was a frequent mild variant, suggesting that deep-intronic variants (DIVs) or other cis-modifiers might have been missed. After single molecule molecular inversion probes (smMIPs)-based sequencing of the complete 128-kb ABCA4 locus, the effect of putative splice variants was assessed in vitro by midigene splice assays in HEK293T cells. The breakpoints of copy number variants (CNVs) were determined by junction PCR and Sanger sequencing. ABCA4 sequence analysis solved 207 of 520 (39.8%) naive or unsolved cases and 70 of 202 (34.7%) monoallelic cases, while additional causal variants were identified in 54 of 136 (39.7%) probands carrying two variants. Seven novel DIVs and six novel non-canonical splice site variants were detected in a total of 35 alleles and characterized, including the c.6283-321C>G variant leading to a complex splicing defect. Additionally, four novel CNVs were identified and characterized in five alleles. These results confirm that smMIPs-based sequencing of the complete ABCA4 gene provides a cost-effective method to genetically solve retinopathy cases and that several rare structural and splice altering defects remain undiscovered in Stargardt disease cases.

Published
2023
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8. Effectiveness and safety of virtual reality rehabilitation after stroke: an overview of systematic reviewsResearch in context

Author

Silvia Bargeri, Sabrina Scalea, Federica Agosta, Giuseppe Banfi, Davide Corbetta, Massimo Filippi, Elisabetta Sarasso, Andrea Turolla, Greta Castellini, and Silvia Gianola

Subjects
Virtual reality, Stroke, Systematic review, Overview, Medicine (General), R5-920
Abstract

Summary: Background: Virtual reality (VR) is an innovative neurorehabilitation modality that has been variously examined in systematic reviews. We assessed VR effectiveness and safety after cerebral stroke. Methods: In this overview of systematic reviews, we searched eleven databases (Cochrane Database of Systematic Reviews, EMBASE, MEDLINE, SCOPUS, ISI Web of Science, CINAHL, PsycINFO, Pedro, Otseeker, Healthevidence.org, Epistemonikos) and grey literature from inception to January 17, 2023. Studies eligible for inclusion were systematic reviews published in English that included adult patients with a clinical diagnosis of stroke (acute to chronic phase) undergoing any kind of immersive, semi-immersive or non-immersive VR intervention with or without conventional therapy versus conventional therapy alone. The primary outcome was motor upper limb function and activity. The secondary outcomes were gait and balance, cognitive and mental function, limitation of activities, participation, and adverse events. We calculated the degree of overlap between reviews based on the corrected covered area (CCA). Methodological quality was assessed using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR 2) and the Certainty of Evidence (CoE) using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Discordances between results were examined using a conceptual framework based on the Jadad algorithm. This overview is registered with PROSPERO, CRD42022329263. Findings: Of the 58 reviews included (n = 345 unique primary studies), 42 (72.4%) had conducted meta-analysis. More than half of the reviews (58.6%) were published between 2020 and 2022 and many (77.6%) were judged critically low in quality by AMSTAR 2. Most reported the Fugl Meyer Assessment scale (FMA-UE) to measure upper limb function and activity. For the primary outcome, there was a moderate overlap of primary studies (CCA 9.0%) with discordant findings. Focusing on upper limb function (FMA-UE), VR with or without conventional therapy seems to be more effective than conventional therapy alone, with low to moderate CoE and probable to definite clinical relevance. For secondary outcomes there was uncertainty about the superiority or no difference between groups due to substantial heterogeneity of measurement scales (eg, methodological choices). A few reviews (n = 6) reported the occurrence of mild adverse events. Interpretation: Current evidence suggests that multiple meta-analyses agreed on the superiority of VR with or without conventional therapy over conventional therapy on FME-UE for upper limb. Clinicians may consider embedding VR technologies into their practice as appropriate with patient's goals, abilities, and preferences. However, caution is needed given the poor methodological quality of reviews. Funding: Italian Ministry of Health.

Published
2023
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9. Osteoporosis and Covid-19: Detected similarities in bone lacunar-level alterations via combined AI and advanced synchrotron testing

Author

Federica Buccino, Luigi Zagra, Elena Longo, Lorenzo D'Amico, Giuseppe Banfi, Filippo Berto, Giuliana Tromba, and Laura Maria Vergani

Subjects
Bone lacunae, Micro-scale, Synchrotron, Osteoporosis, Covid-19, Materials of engineering and construction. Mechanics of materials, TA401-492
Abstract

While advanced imaging strategies have improved the diagnosis of bone-related pathologies, early signs of bone alterations remain difficult to detect. The Covid-19 pandemic has brought attention to the need for a better understanding of bone micro-scale toughening and weakening phenomena. This study used an artificial intelligence-based tool to automatically investigate and validate four clinical hypotheses by examining osteocyte lacunae on a large scale with synchrotron image-guided failure assessment. The findings indicate that trabecular bone features exhibit intrinsic variability related to external loading, micro-scale bone characteristics affect fracture initiation and propagation, osteoporosis signs can be detected at the micro-scale through changes in osteocyte lacunar features, and Covid-19 worsens micro-scale porosities in a statistically significant manner similar to the osteoporotic condition. Incorporating these findings with existing clinical and diagnostic tools could prevent micro-scale damages from progressing into critical fractures.

Published
2023
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10. Clinical, genetic, epidemiologic, evolutionary, and functional delineation of TSPEAR-related autosomal recessive ectodermal dysplasia 14

Author

Adam Jackson, Sheng-Jia Lin, Elizabeth A. Jones, Kate E. Chandler, David Orr, Celia Moss, Zahra Haider, Gavin Ryan, Simon Holden, Mike Harrison, Nigel Burrows, Wendy D. Jones, Mary Loveless, Cassidy Petree, Helen Stewart, Karen Low, Deirdre Donnelly, Simon Lovell, Konstantina Drosou, Gaurav K. Varshney, Siddharth Banka, J.C. Ambrose, P. Arumugam, R. Bevers, M. Bleda, F. Boardman-Pretty, C.R. Boustred, H. Brittain, M.A. Brown, M.J. Caulfield, G.C. Chan, A. Giess, J.N. Griffin, A. Hamblin, S. Henderson, T.J.P. Hubbard, R. Jackson, L.J. Jones, D. Kasperaviciute, M. Kayikci, A. Kousathanas, L. Lahnstein, A. Lakey, S.E.A. Leigh, I.U.S. Leong, F.J. Lopez, F. Maleady-Crowe, M. McEntagart, F. Minneci, J. Mitchell, L. Moutsianas, M. Mueller, N. Murugaesu, A.C. Need, P. O‘Donovan, C.A. Odhams, C. Patch, D. Perez-Gil, M.B. Pereira, J. Pullinger, T. Rahim, A. Rendon, T. Rogers, K. Savage, K. Sawant, R.H. Scott, A. Siddiq, A. Sieghart, S.C. Smith, A. Sosinsky, A. Stuckey, M. Tanguy, A.L. Taylor Tavares, E.R.A. Thomas, S.R. Thompson, A. Tucci, M.J. Welland, E. Williams, K. Witkowska, S.M. Wood, M. Zarowiecki, Olaf Riess, Tobias B. Haack, Holm Graessner, Birte Zurek, Kornelia Ellwanger, Stephan Ossowski, German Demidov, Marc Sturm, Julia M. Schulze-Hentrich, Rebecca Schüle, Christoph Kessler, Melanie Wayand, Matthis Synofzik, Carlo Wilke, Andreas Traschütz, Ludger Schöls, Holger Hengel, Peter Heutink, Han Brunner, Hans Scheffer, Nicoline Hoogerbrugge, Alexander Hoischen, Peter A.C. ’t Hoen, Lisenka E.L.M. Vissers, Christian Gilissen, Wouter Steyaert, Karolis Sablauskas, Richarda M. de Voer, Erik-Jan Kamsteeg, Bart van de Warrenburg, Nienke van Os, Iris te Paske, Erik Janssen, Elke de Boer, Marloes Steehouwer, Burcu Yaldiz, Tjitske Kleefstra, Anthony J. Brookes, Colin Veal, Spencer Gibson, Marc Wadsley, Mehdi Mehtarizadeh, Umar Riaz, Greg Warren, Farid Yavari Dizjikan, Thomas Shorter, Ana Töpf, Volker Straub, Chiara Marini Bettolo, Sabine Specht, Jill Clayton-Smith, Elizabeth Alexander, Laurence Faivre, Christel Thauvin, Antonio Vitobello, Anne-Sophie Denommé-Pichon, Yannis Duffourd, Emilie Tisserant, Ange-Line Bruel, Christine Peyron, Aurore Pélissier, Sergi Beltran, Ivo Glynne Gut, Steven Laurie, Davide Piscia, Leslie Matalonga, Anastasios Papakonstantinou, Gemma Bullich, Alberto Corvo, Carles Garcia, Marcos Fernandez-Callejo, Carles Hernández, Daniel Picó, Ida Paramonov, Hanns Lochmüller, Gulcin Gumus, Virginie Bros-Facer, Ana Rath, Marc Hanauer, Annie Olry, David Lagorce, Svitlana Havrylenko, Katia Izem, Fanny Rigour, Giovanni Stevanin, Alexandra Durr, Claire-Sophie Davoine, Léna Guillot-Noel, Anna Heinzmann, Giulia Coarelli, Gisèle Bonne, Teresinha Evangelista, Valérie Allamand, Isabelle Nelson, Rabah Ben Yaou, Corinne Metay, Bruno Eymard, Enzo Cohen, Antonio Atalaia, Tanya Stojkovic, Milan Macek, Jr., Marek Turnovec, Dana Thomasová, Radka Pourová Kremliková, Vera Franková, Markéta Havlovicová, Vlastimil Kremlik, Helen Parkinson, Thomas Keane, Dylan Spalding, Alexander Senf, Peter Robinson, Daniel Danis, Glenn Robert, Alessia Costa, Christine Patch, Mike Hanna, Henry Houlden, Mary Reilly, Jana Vandrovcova, Francesco Muntoni, Irina Zaharieva, Anna Sarkozy, Vincent Timmerman, Jonathan Baets, Liedewei Van de Vondel, Danique Beijer, Peter de Jonghe, Vincenzo Nigro, Sandro Banfi, Annalaura Torella, Francesco Musacchia, Giulio Piluso, Alessandra Ferlini, Rita Selvatici, Rachele Rossi, Marcella Neri, Stefan Aretz, Isabel Spier, Anna Katharina Sommer, Sophia Peters, Carla Oliveira, Jose Garcia Pelaez, Ana Rita Matos, Celina São José, Marta Ferreira, Irene Gullo, Susana Fernandes, Luzia Garrido, Pedro Ferreira, Fátima Carneiro, Morris A. Swertz, Lennart Johansson, Joeri K. van der Velde, Gerben van der Vries, Pieter B. Neerincx, Dieuwke Roelofs-Prins, Sebastian Köhler, Alison Metcalfe, Alain Verloes, Séverine Drunat, Caroline Rooryck, Aurelien Trimouille, Raffaele Castello, Manuela Morleo, Michele Pinelli, Alessandra Varavallo, Manuel Posada De la Paz, Eva Bermejo Sánchez, Estrella López Martín, Beatriz Martínez Delgado, F. Javier Alonso García de la Rosa, Andrea Ciolfi, Bruno Dallapiccola, Simone Pizzi, Francesca Clementina Radio, Marco Tartaglia, Alessandra Renieri, Elisa Benetti, Peter Balicza, Maria Judit Molnar, Ales Maver, Borut Peterlin, Alexander Münchau, Katja Lohmann, Rebecca Herzog, Martje Pauly, Alfons Macaya, Anna Marcé-Grau, Andres Nascimiento Osorio, Daniel Natera de Benito, Rachel Thompson, Kiran Polavarapu, David Beeson, Judith Cossins, Pedro M. Rodriguez Cruz, Peter Hackman, Mridul Johari, Marco Savarese, Bjarne Udd, Rita Horvath, Gabriel Capella, Laura Valle, Elke Holinski-Feder, Andreas Laner, Verena Steinke-Lange, Evelin Schröck, and Andreas Rump

Subjects
TSPEAR, Ectodermal dysplasia, Enamel knot, WNT10A, Hypodontia, Conical teeth, Genetics, QH426-470
Abstract

Summary: TSPEAR variants cause autosomal recessive ectodermal dysplasia (ARED) 14. The function of TSPEAR is unknown. The clinical features, the mutation spectrum, and the underlying mechanisms of ARED14 are poorly understood. Combining data from new and previously published individuals established that ARED14 is primarily characterized by dental anomalies such as conical tooth cusps and hypodontia, like those seen in individuals with WNT10A-related odontoonychodermal dysplasia. AlphaFold-predicted structure-based analysis showed that most of the pathogenic TSPEAR missense variants likely destabilize the β-propeller of the protein. Analysis of 100000 Genomes Project (100KGP) data revealed multiple founder TSPEAR variants across different populations. Mutational and recombination clock analyses demonstrated that non-Finnish European founder variants likely originated around the end of the last ice age, a period of major climatic transition. Analysis of gnomAD data showed that the non-Finnish European population TSPEAR gene-carrier rate is ∼1/140, making it one of the commonest AREDs. Phylogenetic and AlphaFold structural analyses showed that TSPEAR is an ortholog of drosophila Closca, an extracellular matrix-dependent signaling regulator. We, therefore, hypothesized that TSPEAR could have a role in enamel knot, a structure that coordinates patterning of developing tooth cusps. Analysis of mouse single-cell RNA sequencing (scRNA-seq) data revealed highly restricted expression of Tspear in clusters representing enamel knots. A tspeara−/−;tspearb−/− double-knockout zebrafish model recapitulated the clinical features of ARED14 and fin regeneration abnormalities of wnt10a knockout fish, thus suggesting interaction between tspear and wnt10a. In summary, we provide insights into the role of TSPEAR in ectodermal development and the evolutionary history, epidemiology, mechanisms, and consequences of its loss of function variants.

Published
2023
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11. Improving chestnut physicochemical properties through fermentation – Development of chestnut Amazake

Author

Marisa V. Santos, Stefano Banfi, Rafaela Santos, Mariana Mota, Anabela Raymundo, and Catarina Prista

Subjects
Fermented foods, Amazake, Chestnut, Texture, Physicochemical composition, Linear viscoelastic behaviour, Nutrition. Foods and food supply, TX341-641, Food processing and manufacture, TP368-456
Abstract

The increased awareness of population regarding the impact of consumption habits is leading to interest in new, innovative, diversified and health promoting foods. In this work, two new amazake fermented products were developed with chestnut (Castanea sativa Mill.), using rice or chestnut koji as source of glycolytic enzymes. The analysis of the amazakes evolution showed improvements in chestnuts physicochemical characteristics. The fermented products presented higher values of soluble protein, sugars, starches, antioxidant capacity, and similar values of ascorbic acid for chestnut koji amazake. The adhesiveness increased, which is related to the enhanced concentrations of sugars and starches. The evolution into less structured products was observed in the firmness followed by a consistent decrease of the viscoelastic moduli.The developed chestnut amazakes can represent a suitable alternative to traditional amazake, creating an opportunity for valorisation of chestnut industrial by-products, as new, tasty, and nutritive fermented products with potential functional characteristics.

Published
2023
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12. Ultrafast nano generation of acoustic waves in water via a single carbon nanotube

Author

Michele Diego, Marco Gandolfi, Alessandro Casto, Francesco Maria Bellussi, Fabien Vialla, Aurélien Crut, Stefano Roddaro, Matteo Fasano, Fabrice Vallée, Natalia Del Fatti, Paolo Maioli, and Francesco Banfi

Subjects
Ultrafast photoacoustics, Acoustic waves, Hypersonic, Photothermal, Carbon nanotubes, Nanoscale heat transfer, Physics, QC1-999, Acoustics. Sound, QC221-246, Optics. Light, QC350-467
Abstract

Generation of ultra high frequency acoustic waves in water is key to nano resolution sensing, acoustic imaging and theranostics. In this context water immersed carbon nanotubes (CNTs) may act as an ideal optoacoustic source, due to their nanometric radial dimensions, peculiar thermal properties and broad band optical absorption. The generation mechanism of acoustic waves in water, upon excitation of both a single-wall (SW) and a multi-wall (MW) CNT with laser pulses of temporal width ranging from 5 ns down to ps, is theoretically investigated via a multiscale approach. We show that, depending on the combination of CNT size and laser pulse duration, the CNT can act as a thermophone or a mechanophone. As a thermophone, the CNT acts as a nanoheater for the surrounding water, which, upon thermal expansion, launches the pressure wave. As a mechanophone, the CNT acts as a nanopiston, its thermal expansion directly triggering the pressure wave in water. Activation of the mechanophone effect is sought to trigger few nanometers wavelength sound waves in water, matching the CNT acoustic frequencies. This is at variance with respect to the commonly addressed case of water-immersed single metallic nano-objects excited with ns laser pulses, where only the thermophone effect significantly contributes. The present findings might be of impact in fields ranging from nanoscale non-destructive testing to water dynamics at the meso to nanoscale.

Published
2022
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13. Effect of surface tension and drying time on inkjet-printed PEDOT:PSS for ITO-free OLED devices

Author

Marco Cinquino, Carmela Tania Prontera, Alessandra Zizzari, Antonella Giuri, Marco Pugliese, Roberto Giannuzzi, Anna Grazia Monteduro, Matteo Carugati, Augusto Banfi, Sonia Carallo, Aurora Rizzo, Antonio Andretta, Giovanni Dugnani, Giuseppe Gigli, and Vincenzo Maiorano

Subjects
PEDOT:PSS, Surface tension, Co-solvent, Inkjet printing, Organic light-emitting diodes, ITO-Free, Materials of engineering and construction. Mechanics of materials, TA401-492
Abstract

Highly conductive PEDOT:PSS is one of the most promising materials for indium tin oxide (ITO) substitution in printed electronics. Here, we report the development and optimisation of two PEDOT:PSS ink formulations for the fabrication of inkjet-printed transparent conductive layers. Starting from aqueous commercial solutions, co-solvents and a non-ionic surfactant were employed to modify the surface tension, improve the wetting capability of the ink, and obtain uniform and homogeneous thin films. In particular, the quantities of ethanol and surfactant were systematically adjusted to determine the optimal conditions for inkjet printing. The results demonstrate that a surface tension value between 28 and 40 mN/m and approximately 40 vol.% of a low-boiling-point co-solvent are fundamental to ensure the proper wetting of the glass substrate and a quick-drying process that confers uniformity to the printed thin film. The printed PEDOT:PSS thin films show good morphological, optical, and electrical properties that are similar to those observed for the corresponding spin-coated layers. The organic light-emitting diodes (OLEDs) fabricated with the inkjet-printed PEDOT:PSS electrodes showed a maximum quantum efficiency of 5.5% and a maximum current efficiency of 15 cd/A, which is comparable to spin-coated reference devices. Our study demonstrates the great potential of polymeric electrodes for the fabrication of high-efficiency printed OLED devices that are compatible with flexible and stretchable substrates.

Published
2022
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14. Liquiritigenin reduces osteoclast activity in zebrafish model of glucocorticoid-induced osteoporosis

Author

Marta Carnovali, Giuseppe Banfi, and Massimo Mariotti

Subjects
Zebrafish, Liquiritigenin, Osteoporosis, Bone metabolism, Scales, Therapeutics. Pharmacology, RM1-950
Abstract

Drug and therapies currently used to treat human bone diseases have a lot of severe side effects. Liquiritigenin is a flavonoid extracted from Glycyrrhiza glabra roots which has been reported to have positive effects in vitro on osteoblasts activity and bone mineralization as well as inhibitory effect on osteoclasts differentiation and activity in vitro. The present study was aimed to evaluate the in vivo effects of liquiritigenin on bone structure and metabolism in physiological and pathological conditions using Danio rerio as experimental animal model. Treatments with liquiritigenin were performed on embryos to evaluate the osteogenesis during skeletal development. Other treatments were performed on adult fish affected by glucocorticoid-induced osteoporosis to assay the therapeutic potential of liquiritigenin in the reversion of bone-loss phenotype in scale model. Liquiritigenin treatment of zebrafish embryo significantly enhances the osteogenesis during development in a dose-dependent manner. In addition, liquiritigenin inhibits the formation of the osteoporotic phenotype in adult zebrafish model of glucocorticoid-induced osteoporosis preventing osteoclast activation in scales. Interestingly, liquiritigenin does not counteract the loss of osteoblastic activity in scales. The liquiritigenin exhibits in vivo anti-osteoporotic activity on adult fish scale model. It can be considered a good candidate to develop new drugs against osteoporosis.

Published
2020
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15. Lipid peroxidation derived reactive carbonyl species in free and conjugated forms as an index of lipid peroxidation: limits and perspectives

Author

Alessandra Altomare, Giovanna Baron, Erica Gianazza, Cristina Banfi, Marina Carini, and Giancarlo Aldini

Subjects
Lipid peroxidation, Reactive carbonyl species, Covalent adducts, Protein carbonylation, Analytical methods, Biomarkers, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Reactive carbonyl species (RCS) formed by lipidperoxidation as free forms or as enzymatic and non-enzymatic conjugates are widely used as an index of oxidative stress. Besides general measurements based on derivatizing reactions, more selective and sensitive MS based analyses have been proposed in the last decade. Untargeted and targeted methods for the measurement of free RCS and adducts have been described and their applications to in vitro and ex vivo samples have permitted the identification of many biological targets, reaction mechanisms and adducted moieties with a particular relevance to RCS protein adducts. The growing interest in protein carbonylation can be explained by considering that protein adducts are now recognized as being involved in the damaging action of oxidative stress so that their measurement is performed not only to obtain an index of lipid peroxidation but also to gain a deeper insight into the molecular mechanisms of oxidative stress. The aim of the review is to discuss the most novel analytical approaches and their application for profiling reactive carbonyl species and their enzymatic and non-enzymatic metabolites as an index of lipid-oxidation and oxidative stress. Limits and perspectives will be discussed.

Published
2021
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16. Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry

Author

Jitendra PS. Sawhney, Veerappa A. Kothiwale, Vikas Bisne, Rajashekhar Durgaprasad, Praveen Jadhav, Manoj Chopda, Velam Vanajakshamma, Ramdhan Meena, Govindan Vijayaraghavan, Kamaldeep Chawla, Jagan Allu, Karen S. Pieper, A. John Camm, Ajay K. Kakkar, Jean-Pierre Bassand, David A. Fitzmaurice, Samuel Z. Goldhaber, Shinya Goto, Sylvia Haas, Werner Hacke, Lorenzo G. Mantovani, Frank Misselwitz, Alexander G.G. Turpie, Martin van Eickels, Freek W.A. Verheugt, Gloria Kayani, Keith A.A. Fox, Bernard J. Gersh, Hector Lucas Luciardi, Harry Gibbs, Marianne Brodmann, Frank Cools, Antonio Carlos Pereira Barretto, Stuart J. Connolly, Alex Spyropoulos, John Eikelboom, Ramon Corbalan, Dayi Hu, Petr Jansky, Jørn Dalsgaard Nielsen, Hany Ragy, Pekka Raatikainen, Jean-Yves Le Heuzey, Harald Darius, Matyas Keltai, Sanjay Kakkar, Jitendra Pal Singh Sawhney, Giancarlo Agnelli, Giuseppe Ambrosio, Yukihiro Koretsune, Carlos Jerjes Sánchez Díaz, Hugo Ten Cate, Dan Atar, Janina Stepinska, Elizaveta Panchenko, Toon Wei Lim, Barry Jacobson, Seil Oh, Xavier Viñolas, Marten Rosenqvist, Jan Steffel, Pantep Angchaisuksiri, Ali Oto, Alex Parkhomenko, Wael Al Mahmeed, David Fitzmaurice, D.Y. Hu, K.N. Chen, Y.S. Zhao, H.Q. Zhang, J.Z. Chen, S.P. Cao, D.W. Wang, Y.J. Yang, W.H. Li, Y.H. Yin, G.Z. Tao, P. Yang, Y.M. Chen, S.H. He, Ying Wang, Yong Wang, G.S. Fu, X. Li, T.G. Wu, X.S. Cheng, X.W. Yan, R.P. Zhao, M.S. Chen, L.G. Xiong, P. Chen, Y. Jiao, Y. Guo, L. Xue, F.Z. Wang, H. Li, Z.M. Yang, C.L. Bai, J. Chen, J.Y. Chen, X. Chen, S. Feng, Q.H. Fu, X.J. Gao, W.N. Guo, R.H. He, X.A. He, X.S. Hu, X.F. Huang, B. Li, J. Li, L. Li, Y.H. Li, T.T. Liu, W.L. Liu, Y.Y. Liu, Z.C. Lu, X.L. Luo, T.Y. Ma, J.Q. Peng, X. Sheng, X.J. Shi, Y.H. Sun, G. Tian, K. Wang, L. Wang, R.N. Wu, Q. Xie, R.Y. Xu, J.S. Yang, L.L. Yang, Q. Yang, Y. Ye, H.Y. Yu, J.H. Yu, T. Yu, H. Zhai, Q. Zhan, G.S. Zhang, Q. Zhang, R. Zhang, Y. Zhang, W.Y. Zheng, B. Zhou, Z.H. Zhou, X.Y. Zhu, S. Kakkar, J.P.S. Sawhney, P. Jadhav, R. Durgaprasad, A.G. Ravi Shankar, R.K. Rajput, K. Bhargava, R. Sarma, A. Srinivas, D. Roy, U.M. Nagamalesh, M. Chopda, R. Kishore, G. Kulkarni, P. Chandwani, R.A. Pothiwala, M. Padinhare Purayil, S. Shah, K. Chawla, V.A. Kothiwale, B. Raghuraman, G. Vijayaraghavan, V.M. Vijan, G. Bantwal, V. Bisne, A. Khan, J.B. Gupta, S. Kumar, D. Jain, S. Abraham, D. Adak, A. Barai, H. Begum, P. Bhattacharjee, M. Dargude, D. Davies, B. Deshpande, P. Dhakrao, V. Dhyani, S. Duhan, M. Earath, A. Ganatra, S. Giradkar, V. Jain, R. Karthikeyan, L. Kasala, S. Kaur, S. Krishnappa, A. Lawande, B. Lokesh, N. Madarkar, R. Meena, P. More, D. Naik, K. Prashanth, M. Rao, N.M. Rao, N. Sadhu, D. Shah, M. Sharma, P. Shiva, S. Singhal, S. Suresh, V. Vanajakshamma, S.G. Panse, Y. Koretsune, S. Kanamori, K. Yamamoto, K. Kumagai, Y. Katsuda, K. Sadamatsu, F. Toyota, Y. Mizuno, I. Misumi, H. Noguchi, S. Ando, T. Suetsugu, M. Minamoto, Hiroshi Oda, K. Shiraishi, S. Adachi, K. Chiba, H. Norita, M. Tsuruta, T. Koyanagi, H. Ando, T. Higashi, K. Okada, S. Azakami, S. Komaki, K. Kumeda, T. Murayama, J. Matsumura, Y. Oba, R. Sonoda, K. Goto, K. Minoda, Y. Haraguchi, H. Suefuji, H. Miyagi, H. Kato, Tadashi Nakamura, Tsugihiro Nakamura, H. Nandate, R. Zaitsu, Yoshihisa Fujiura, A. Yoshimura, H. Numata, J. Ogawa, H. Tatematsu, Y. Kamogawa, K. Murakami, Y. Wakasa, M. Yamasawa, H. Maekawa, S. Abe, H. Kihara, S. Tsunoda, Katsumi Saito, Kazuyuki Saito, T. Fudo, K. Obunai, H. Tachibana, I. Oba, T. Kuwahata, S. Higa, M. Gushiken, T. Eto, H. Yoshida, D. Ikeda, Yoshitake Fujiura, M. Ishizawa, M. Nakatsuka, K. Murata, C. Ogurusu, M. Shimoyama, M. Akutsu, I. Takamura, F. Hoshino, N. Yokota, T. Iwao, K. Tsuchida, M. Takeuchi, Y. Hatori, Y. Kitami, Yoichi Nakamura, R. Oyama, M. Ageta, Hiroyuki Oda, Y. Go, K. Mishima, T. Unoki, S. Morii, Yuhei Shiga, H. Sumi, T. Nagatomo, K. Sanno, K. Fujisawa, Y. Atsuchi, T. Nagoshi, T. Seto, T. Tabuchi, M. Kameko, K. Nii, K. Oshiro, H. Takezawa, S. Nagano, N. Miyamoto, M. Iwaki, Yuichiro Nakamura, M. Fujii, M. Okawa, Masahiko Abe, Masatake Abe, Mitsunori Abe, T. Saito, T. Mito, K. Nagao, J. Minami, T. Mita, I. Sakuma, T. Taguchi, S. Marusaki, H. Doi, M. Tanaka, T. Fujito, M. Matsuta, T. Kusumoto, S. Kakinoki, K. Ashida, N. Yoshizawa, J. Agata, O. Arasaki, M. Manita, M. Ikemura, S. Fukuoka, H. Murakami, S. Matsukawa, Y. Hata, T. Taniguchi, T. Ko, H. Kubo, M. Imamaki, M. Akiyama, M. Inagaki, H. Odakura, T. Ueda, Y. Katsube, A. Nakata, H. Watanabe, M. Techigawara, M. Igarashi, K. Taga, T. Kimura, S. Tomimoto, M. Shibuya, M. Nakano, K. Ito, T. Seo, S. Hiramitsu, H. Hosokawa, M. Hoshiai, M. Hibino, K. Miyagawa, Hajime Horie, N. Sugishita, Yukio Shiga, A. Soma, K. Neya, Tetsuro Yoshida, Tomoki Yoshida, M. Mizuguchi, M. Ishiguro, T. Minagawa, M. Wada, H. Mukawa, F. Okuda, S. Nagasaka, Y. Abe, Sen Adachi, Susumu Adachi, T. Adachi, K. Akahane, T. Amano, K. Aoki, T. Aoyama, H. Arai, S. Arima, T. Arino, H. Asano, T. Asano, J. Azuma, T. Baba, T. Betsuyaku, H. Chibana, H. Date, J. Doiuchi, Y. Emura, M. Endo, Y. Fujii, R. Fujiki, A. Fujisawa, Y. Fujisawa, T. Fukuda, T. Fukui, N. Furukawa, T. Furukawa, W. Furumoto, T. Goto, M. Hamaoka, N. Hanazono, K. Hasegawa, T. Hatsuno, Y. Hayashi, K. Higuchi, K. Hirasawa, H. Hirayama, M. Hirose, S. Hirota, M. Honda, Hideki Horie, T. Ido, O. Iiji, H. Ikeda, K. Ikeda, K. Ikeoka, M. Imaizumi, H. Inaba, T. Inoue, F. Iseki, A. Ishihara, N. Ishioka, N. Ito, T. Iwase, H. Kakuda, J. Kamata, H. Kanai, H. Kanda, M. Kaneko, H. Kano, T. Kasai, T. Kato, Y. Kato, Y. Kawada, K. Kawai, K. Kawakami, S. Kawakami, T. Kawamoto, S. Kawano, J. Kim, T. Kira, H. Kitazawa, H. Kitazumi, T. Kito, T. Kobayashi, T. Koeda, J. Kojima, H. Komatsu, I. Komatsu, Y. Koshibu, T. Kotani, T. Kozuka, Y. Kumai, T. Kumazaki, I. Maeda, K. Maeda, Y. Maruyama, S. Matsui, K. Matsushita, Y. Matsuura, K. Mineoi, H. Mitsuhashi, N. Miura, S. Miyaguchi, S. Miyajima, H. Miyamoto, A. Miyashita, S. Miyata, I. Mizuguchi, A. Mizuno, T. Mori, O. Moriai, K. Morishita, O. Murai, Sho Nagai, Shunichi Nagai, E. Nagata, H. Nagata, A. Nakagomi, S. Nakahara, M. Nakamura, R. Nakamura, N. Nakanishi, T. Nakayama, R. Nakazato, T. Nanke, J. Nariyama, Y. Niijima, H. Niinuma, Y. Nishida, Y. Nishihata, K. Nishino, H. Nishioka, K. Nishizawa, I. Niwa, K. Nomura, S. Nomura, M. Nozoe, T. Ogawa, N. Ohara, M. Okada, K. Okamoto, H. Okita, M. Okuyama, H. Ono, T. Ono, Y. Onuki Pearce, S. Oriso, A. Ota, E. Otaki, Y. Saito, H. Sakai, N. Sakamoto, Y. Sakamoto, Y. Samejima, Y. Sasagawa, H. Sasaguri, A. Sasaki, T. Sasaki, Kazuki Sato, Kiyoharu Sato, M. Sawano, S. Seki, Y. Sekine, Y. Seta, K. Sezaki, N. Shibata, Y. Shiina, H. Shimono, Y. Shimoyama, T. Shindo, H. Shinohara, R. Shinohe, T. Shinozuka, T. Shirai, T. Shiraiwa, Y. Shozawa, T. Suga, C. Sugimoto, Kazuo Suzuki, Keita Suzuki, Shu Suzuki, Shunji Suzuki, Susumu Suzuki, Y. Suzuki, M. Tada, A. Taguchi, T. Takagi, Y. Takagi, K. Takahashi, S. Takahashi, H. Takai, C. Takanaka, S. Take, H. Takeda, K. Takei, K. Takenaka, T. Tana, G. Tanabe, K. Taya, H. Teragawa, S. Tohyo, S. Toru, Y. Tsuchiya, T. Tsuji, K. Tsuzaki, H. Uchiyama, O. Ueda, Y. Ueyama, N. Wakaki, T. Wakiyama, T. Washizuka, M. Watanabe, T. Yamada, T. Yamagishi, H. Yamaguchi, Kenichi Yamamoto, Kentaro Yamamoto, Kunihiko Yamamoto, T. Yamamoto, M. Yamaura, M. Yamazoe, K. Yasui, Y. Yokoyama, K. Yoshida, T.W. Lim, C.K. Ching, C.G. Foo, J.H. Chow, D.D. Chen, F.R. Jaufeerally, Y.M. Lee, G. Lim, W.T. Lim, S. Thng, S.Y. Yap, C. Yeo, S. Oh, H.N. Pak, J.-B. Kim, J.H. Kim, S.-W. Jang, D.H. Kim, D.R. Ryu, S.W. Park, D.-K. Kim, D.J. Choi, Y.S. Oh, M.-C. Cho, S.-H. Kim, H.-K. Jeon, D.-G. Shin, J.S. Park, H.K. Park, S.-J. Han, J.H. Sung, J.-G. Cho, G.-B. Nam, Y.K. On, H.E. Lim, J.J. Kwak, T.-J. Cha, T.J. Hong, S.H. Park, J.H. Yoon, N.-H. Kim, K.-S. Kim, B.C. Jung, G.-S. Hwang, C.-J. Kim, D.B. Kim, J.J. Ahn, H.J. An, H. Bae, A.L. Baek, W.J. Chi, E.A. Choi, E.H. Choi, H.K. Choi, H.S. Choi, S. Han, E.S. Heo, K.O. Her, S.W. Hwang, E.M. Jang, H.-S. Jang, S. Jang, H.-G. Jeon, S.R. Jeon, Y.R. Jeon, H.K. Jeong, I.-A. Jung, Hyeon Jeong Kim, Hyun Ju Kim, Ji Seon Kim, Jung Sook Kim, J.A. Kim, K.T. Kim, M.S. Kim, Sang Hee Kim, Sang Hyun Kim, Y.-I. Kim, C.S. Lee, E.H. Lee, G.H. Lee, H.Y. Lee, H.-Y. Lee, K.H. Lee, K.R. Lee, M.S. Lee, M.-Y. Lee, R.W. Lee, S.E. Lee, S.H. Lee, S. Lee, W.Y. Lee, I.K. Noh, A.R. Park, B.R. Park, H.N. Park, J.H. Park, M. Park, Y. Park, S.-Y. Seo, J. Shim, J.H. Sim, Y.M. Sohn, W.S. Son, Y.S. Son, H.J. Song, H.K. Wi, J.J. Woo, S. Ye, K.H. Yim, K.M. Yoo, E.J. Yoon, S.Y. Yun, P. Angchaisuksiri, S. Chawanadelert, P. Mongkolwongroj, K. Kanokphatcharakun, S. Cheewatanakornkul, T. Laksomya, S. Pattanaprichakul, T. Chantrarat, S. Rungaramsin, S. Silaruks, W. Wongcharoen, K. Siriwattana, K. Likittanasombat, P. Katekangplu, W. Boonyapisit, D. Cholsaringkarl, B. Chatlaong, P. Chattranukulchai, Y. Santanakorn, P. Hutayanon, P. Khunrong, T. Bunyapipat, S. Jai-Aue, P. Kaewsuwanna, P. Bamungpong, S. Gunaparn, S. Hongsuppinyo, R. Inphontan, R. Khattaroek, K. Khunkong, U. Kitmapawanont, C. Kongsin, B. Naratreekoon, S. Ninwaranon, J. Phangyota, A. Phrommintikul, P. Phunpinyosak, K. Pongmorakot, S. Poomiphol, N. Pornnimitthum, S. Pumprueg, S. Ratchasikaew, K. Sanit, K. Sawanyawisuth, B. Silaruks, R. Sirichai, A. Sriwichian, W. Suebjaksing, P. Sukklad, T. Suttana, A. Tangsirira, O. Thangpet, W. Tiyanon, Y. Vorasettakarnkij, T. Wisaratapong, W. Wongtheptien, A. Wutthimanop, S. Yawila, A. Oto, A. Altun, I. Ozdogru, K. Ozdemir, O. Yilmaz, A. Aydinlar, M.B. Yilmaz, E. Yeter, Z. Ongen, M. Cayli, H. Pekdemir, M. Ozdemir, M. Sucu, T. Sayin, M. Demir, H. Yorgun, M. Ersanli, E. Okuyan, D. Aras, H. Abdelrahman, O. Aktas, D. Alpay, F. Aras, M.F. Bireciklioglu, S. Budeyri, M. Buyukpapuc, S. Caliskan, M. Esen, M.A. Felekoglu, D. Genc, B. Ikitimur, E.B. Karaayvaz, S. Kılıç Karataş, S. Okutucu, E. Ozcelik, A. Quisi, H. Sag, L. Sahiner, B.Y. Sayin, T. Seker, D. Uzun Alkan, E. Yildirim, R. Yildirim, F. Yilmaz, V. Yuksekdag, H.L. Luciardi, N. Vensentini, A.C. Ingaramo, G.A. Sambadaro, V. Fernandez Caputi, S.G. Berman, P. Dragotto, A.J. Kleiban, N. Centurion, G. Giacomi, R.A. Ahuad Guerrero, D. Conde, G. Zapata, L.A. Di Paola, J.L. Ramos, R.D. Dran, J. Egido, A.A. Fernandez, M.J. Fosco, S. Sassone, V.A. Sinisi, L.R. Cartasegna, M.A. Berli, O.A. Gomez Vilamajo, F. Ferroni, E.D. Alaguibe, A. Alvarez D'Amelio, C. Arabetti, L. Arias, J.A. Belardi, L. Bergesio, F. Berli, M. Berli, S. Borchowiec, C. Buzzetti, R. Cabrini, V. Campisi, A.L. Cappi, R. Carrizo, F. Colombo Berra, J.P. Costabel, O.J.A. Costamagna, A.A. Damonte, I.N. De Urquiza, F. Diez, M.F. Edén, M. Fanuele, F. Fernandez Voena, M. Foa Torres, C. Funosas, M.P. Giacomi, C.H. Gimenez, E.P. Gurfinkel, M. de L.M. Had, V. Hansen, A.D. Hrabar, M. Ingratta, A. Lopez, G. Maehara, L. Maffei, A. Martinelli, C. Martinelli, J. Matkovich, B. Mautner, A. Meirino, R. Munguia, A. Navarro, V. Novas, G. Perez Prados, J. Pontoriero, R.N. Potito, C. Ricotti, M.A. Rodriguez, F. Rolandi, M.E. Said Palladino, M. Salinger, L.S. Sanziani, P.O. Schygiel, A. Sossich, J.F. Tinto, L. Tonelli, A.L. Tufare, M. Vallejo, M.E. Yunis, M. Zillo, F.J. Zurbrigk, A.C.P. Barretto, D.C. Sobral Filho, J. Jaber, D. Armaganijan, J. Faria Neto, A. Steffens, W. Kunz Sebba Barroso de Souza, J.D. de Souza Neto, J.M. Ribeiro, M. Silveira Teixeira, P.R. Ferreira Rossi, L. Pires, D. Moreira, J.C. Moura Jorge, A. Menezes Lorga Filho, L.C. Bodanese, M. Westerlund Montera, C.H. Del Carlo, T. Da Rocha Rodrigues, F.A. Alves da Costa, A. Lopes, R. Lopes, G.R. Araújo, E.R. Fernandes Manenti, J.F. Kerr Saraiva, J.C. Ferreira Braga, A. Negri, L. Souto, C. Moncada, D. Bertolim Precoma, F. Roquette, G. Reis, R.A. Ramos Filho, E. Lanna Figueiredo, R. Vieira Botelho, C. Munhoz da Fontoura Tavares, C.R. Costantini Frack, J. Abdalla Saad, H.C. Finimundi, C. Pisani, D. Chemello, M. Pereira Martins, C.C. Broilo França, F. Alban, G.B. Aranha Rosito, J.B. de Moura Xavier Moraes Junior, R.T. Tumelero, L. Nigro Maia, R. Simões de Almeida, N.C. do Carmo Borges, L.G. Gomes Ferreira, P. Agliardi, J. Alves de Oliveira Gomes, V. Araujo, M. Arruda Nakazone, T. Barbosa, S. Barroso, E. Belisario Falchetto, H. Bellotti Lopes, M.A. Benez Teixeira Lemos, G. Biazus, L. Borges Queiroz, F.E. Camazzola, M. Caporale, S. Cardoso Boscato, F. Chieza, M.O. Chokr, R. Clemente Mingireanov, N. Codonho Góes, C. Correa, M. Costa, C. Costantini Ortiz, L.S. da Silva, F. da Silva Paulitsch, J.A. da Silveira, E. Daros, G.R. de Araújo, M.I. Del Monaco, C. Dias, M.A. Dias, A.P. Drummond Wainstein, P. Ely Pizzato, D.C. Esteves, P. Fabri, T. 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Houzvic, P. Marin Cuevas, H. Montecinos, A. Forero, F. Lanas, M. Larico Gómez, G. Charme Vilches, C. Rey, C. Astudillo, J. Aguilar, Y. Campisto, C. Lara, E. Molina, J. Munoz Oyarzon, V. Olguin, M. Vergara, C. Villan, C.J. Sánchez Díaz, J. Illescas Diaz, R. Leal Cantú, M.G. Ramos Zavala, R. Cabrera Jardines, N. Espinola Zavaleta, S. Villarreal Umaña, E. López Rosas, G. Llamas Esperón, G. Pozas, E. Cardona Muñoz, N. Matadamas Hernández, A. Leyva Rendón, N. García Hernández, M. de los Ríos Ibarra, L. Virgen Carrillo, D. López Villezca, C. Hernández Herrera, J.J. López Prieto, R. Gaona Rodríguez, E. Villeda Espinosa, D. Flores Martínez, J. Velasco Barcena, R. Yong, I. Rodríguez Briones, J.L. Leiva Pons, H. Álvarez López, R. Olvera Ruiz, C. Díaz de la Vega, C. Cantú Brito, E. Chuquiure Valenzuela, R. Reyes-Sanchez, A. Bazzoni Ruiz, O. Nandayapa Flores, M. Benavides Gonzalez, R. Arriaga Nava, J.D. Morales Cerda, O. Fierro Fierro, P. Fajardo Campos, T.A.A. Alfaro, S. Altamirano Bellorin, R. 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Almeida Fernández, N. Del Val Plana, E. Escrivá Montserrat, J.J. Montero Alía, M. Barreda González, M.A. Moleiro Oliva, J. Iglesias Sanmartín, M. Jiménez González, M. Rodriguez Álvarez, J. Herreros Melenchon, T. Ripoll Vera, F. Ridocci Soriano, L. Garcia Riesco, M.D. Marco Macian, J. Quiles Granado, M. Jimenez Navarro, J. Cosin Sales, J.V. Vaquer Perez, M. Vazquez Caamano, M.F. Arcocha Torres, G. Marcos Gomez, A. Iñiguez Romo, M.A. Prieto Diaz, Carmela Alonso, Concepcion Alonso, D. Alvarez, M. Alvarez, M. Amaro, N. Andere, J. Aracil Villar, R. Armitano Ochoa, A. Austria, S. Barbeira, E. Barraquer Feu, A. Bartes, V. Becerra Munoz, F.J. Bermudez Jimenez, A. Branjovich Tijuan, J. Cabeza Ramirez, M. Cabrera Ramos, E. Calvo Martinez, M. Campo Moreno, G. Cancho Corchado, M. Casanova Gil, M. Castillo Orive, D. Castro Fernandez, M. Cebollada del Misterio, R. Codinachs Alsina, A. Cortada Cabrera, J. Costa Pinto Prego de Faria, S. Costas, M.I. Cotilla Marco, M. Dachs, C.M. Diaz Lopez, A. Domenech Borras, A. Elorriaga Madariaga, A. Espallargas, M. Fernandez, E. Fernandez Escobar, E. Fernandez Mas, A. Ferrer, J. Fosch, M. Garcia Bermudez, V. Garcia Millan, M. Gavira Saenz, C. Gines Garcia, C. Gomez, Y. Gomez Perez, A. Gonzales Segovia, P. Gonzalez, L. Grigorian, A. Guerrero Molina, M. del C. Gutierrez del Val, B. Herrero Maeso, E. Hevia Rodriguez, A. Iglesias Garcia, M.J. Jimenez Fernandez, B. Jimeno Besa, P. Juan Salvadores, M.B. Lage Bouzamayor, I. Lasuncion, L.E. Lezcano Gort, M. Llobet Molina, M. Lopez, A. Manzanal Rey, J. Mara Guerra, S. Marcus, A. Martin Vila, M. Martinez Mena, P. Mazon, F. Mendez Zurita, G. Millán, M. Molina, P. Montero Alia, D. Montes, M. Moure Gonzalez, R.B. Munoz Munoz, A. Negrete Palma, H.N. Orellana Figueroa, V.M. Ortega, C. Ortiz Cortes, D. Otero Tomera, N. Palomo Merchan, I. Pareja Ibar, E. Pena Garcia, M. Pereda Armayor, M. Perez Carasa, I. Prieto, V. Quintern, R. Renom, L.M. Rincon Diaz, V. Rios, L. Riquelme Sola, R. Rivera, X. Robiro Robiro, M. Roca, C. Roca Saumell, C. Rodrigo, E. Rodriguez, M. Rodriguez Garcia, S. Saez Jimenez, P. Sanchez Calderon, L. Sanchez Mendez, S. Sanchez Parra, C. Santolaya, M.R. Senan Sanz, A. Seoane Blanco, E. Serralvo, N. Sierra, C. Simon Valero, J. Sorribes Lopez, M. Teixido Fontanillas, M. Terns Riera, G. Tobajas, C. Torres, J. Torres Marques, M. Ubeda Pastor, M. Rosenqvist, A. Wirdby, J. Linden, K. Henriksson, M. Elmersson, A. Egilsson, U. Börjesson, G. Svärd, B. Liu, A. Lindh, L.-B. Olsson, M. Gustavsson, Lars Andersson, Lisbeth Andersson, L. Benson, C. Bothin, A. Hajimirsadeghi, K. Kadir, M. Ericsson, A. Ohlsson, H. Lindvall, P. Svensson, K. Thorne, H. Handel, P. Platonov, B. Eriksson, I. Timberg, K. Romberg, M. Crisby, J.-E. Karlsson, S.A. Jensen, A. Andersson, L. Malmqvist, B. Martinsson, F. Bernsten, J. Engdahl, J. Thulin, A. Hot-Bjelac, P. Stalby, H. Aaröe, E. Ahbeck, H. Ahlmark, F. Al-Khalili, G. Bonkowski, S. Dzeletovic, A.-B. Ekstrand, G.-B. Eriksson, K. Floren, C. Grässjö, S. Hahn, P. Jaensson, B. Jansson, J.-H. Jansson, R.-M. Kangert, A. Koch, D. Kusiak, A. Lettenström, A. Lindberg, C.-J. Lindholm, A. Mannermyr, K. Mansson, M. Millborg, C. Nilsson, A.-M. Ohlin, A. Olofsson, A. Osberg, A. Pedersen, K. Risbecker, K. Rosenberg, J. Samuelsson, M. Shayesteh, K. Skoglund, M. Stjernberg, C. Thorsen, J. Steffel, J.H. Beer, J. Debrunner, D. Amstutz, J. Bruegger, G. Elise, A. Grau, A. Guinand, I. Henriette, E. Saga, S. Winnik, A. Parkhomenko, I. Rudyk, V. Tseluyko, O. Karpenko, S. Zhurba, I. Kraiz, I. Kupnovytska, N. Serediuk, Y. Mostovoy, O. Ushakov, O. Koval, I. Kovalskyi, Y. Svyshchenko, O. Sychov, M. Stanislavchuk, O. Kraydashenko, A. Yagensky, S. Tykhonova, I. Fushtey, R. Belegai, G. Berko, L. Burdeuna, O. Chabanna, I. Daniuk, A. Ivanov, E. Kamenska, P. Kaplan, O. Khyzhnyak, S. Kizim, O. Matova, O. Medentseva, V. Mochonyi, M. Mospan, V. Nemtsova, T. Ovdiienko, O. Palamarchuk, M. Pavelko, R. Petrovskyy, D. Plevak, O. Proshak, S. Pyvovar, L. Rasputina, O. Romanenko, O. Romanova, A. Sapatyi, O. Shumakov, R. Stets, L. Todoriuk, V. Varenov, D. Fitzmaurice, N. Chauhan, D. Goodwin, P. Saunders, R. Evans, J. Leese, P.S. Jhittay, A. Ross, M.S. Kainth, G. Pickavance, J. McDonnell, A. Williams, T. Gooding, H. Wagner, S. Suryani, A. Singal, S. Sircar, R. Bilas, P. Hutchinson, A. Wakeman, M. Stokes, N. Paul, M. Aziz, C. Ramesh, P. Wilson, S. Franklin, S. Fairhead, J. Thompson, V. St Joseph, G. Taylor, D. Tragen, D. Seamark, C. Paul, M. Richardson, A. Jefferies, H. Sharp, H. Jones, C. Giles, M. Page, O. Oginni, J. Aldegather, S. Wetherwell, W. Lumb, P. Evans, F. Scouller, N. Macey, Y. Stipp, R. West, S. Thurston, P. Wadeson, J. Matthews, P. Pandya, A. Gallagher, T. Railton, B. Sinha, D. Russell, J.A. Davies, P. Ainsworth, C.P. Jones, P. Weeks, J. Eden, D. Kernick, W. Murdoch, L. Lumley, R.P. Patel, S.W. Wong, M. Saigol, K. Ladha, K. Douglas, D.F. Cumberlidge, C. Bradshaw, G. Van Zon, K.P. Jones, M.J. Thomas, E. Watson, B. Sarai, N. Ahmad, W. Willcock, J. Cairns, S. Sathananthan, N. de Kare-Silver, A. Gilliland, E. Strieder, A. Howitt, B. Vishwanathan, N. Bird, D. Gray, M. Clark, J. Bisatt, J. Litchfield, E. Fisher, T. Fooks, A.R. Kelsall, E. Alborough, J. Wakeling, M. Parfitt, K. Milne, S. Rogers, R. Priyadharshan, J.L. Oliver, E. Davies, S. Abushal, M. Jacobs, C. Hutton, N.I. Walls, R. Thompson, C. Chigbo, S.M.A. Zaidi, M. Howard, K.C. Butter, S. Barrow, H. Little, I.U. Haq, L. Gibbons, S. Glencross, A.J. McLeod, K. Poland, C. Mulholland, A. Warke, P. Conn, G. Burns, R.N. Smith, S. Lowe, R. Kamath, H.S. Dau, J. Webster, I. Hodgins, S. Vercoe, P.C. Roome, H. Pinnock, J.R.A. Patel, A. Ali, N. Hart, R. Davies, E. Stuart, C.A. Neden, M. Danielsen, R. Heath, P. Sharma, S. Galloway, C. Hawkins, R. Oliver, M. Aylward, S. Mannion, M. Braddick, D. Edwards, A.C. Rothwell, A. Sabir, F. Choudhary, S. Khalaque, A. Wilson, S. Peters, W. Coulson, N. Roberts, A. Heer, S. Coates, B. Ward, D. Jackson, S. Walton, D. Shepherd, M. Sterry, T. Wong, M. Boon, R. Bunney, R. Haria-Shah, R.T. Baron, S. Davies, T. Schatzberger, N. Hargreaves, T. Stephenson, H. Choi, R. Batson, L. Lucraft, T. Myhill, S. Estifano, D. Geatch, J. Wilkinson, R. Veale, K. Forshaw, T. Davies, K. Zaman, P. Vinson, C. Liley, M. Bandrapalli, P. McGinty, R. Wastling, P. McEleny, A. Beattie, P. Cooke, M. Wong, J. Gunasegaram, M. Pugsley, S. Ahmad, C. A'Court, J. Ayers, J. Bennett, S. Cartwright, S. Dobson, C. Dooldeniya, A. Flynn, R. Fox, J. Goram, A. Halpin, A. Hay, P. Jacobs, L. Jeffers, L. Lomax, I. Munro, R. Muvva, M. Nadaph, K. Powell, S. Randfield, D. Redpath, R. Reed, M. Rickenbach, G. Rogers, P.B. Saunders, C. Seamark, J. Shewring, P. Simmons, H. Simper, H. Stoddart, A. Sword, N. Thomas, A. Thomson, H. Gibbs, A. Blenkhorn, B. Singh, W. Van Gaal, W. Abhayaratna, R. Lehman, P. Roberts-Thomson, J. Kilian, D. Coulshed, A. Catanchin, D. Colquhoun, H. Kiat, D. Eccleston, J. French, L. Zimmett, B. Ayres, T. Phan, P. Blombery, D. Crimmins, D. O'Donnell, A. Choi, P. Astridge, M. Arstall, N. Jepson, M. Binnekamp, A. Lee, J. Rogers, G. Starmer, P. Carroll, J. Faunt, A. Aggarwala, L. Barry, C. Batta, R. Beveridge, A. Black, M. Bonner, J. Boys, E. Buckley, M. Campo, L. Carlton, A. Connelly, B. Conway, D. Cresp, H. Dimitri, S. Dixon, M. Dolman, M. Duroux, M. Eskandari, R. Eslick, A. Ferreira-Jardim, T. Fetahovic, D. Fitzpatrick, R. Geraghty, J. Gibbs, T. Grabek, M.H. Modi, K. Hayes, M.P. Hegde, L. Hesketh, B. Hoffmann, B. Jacobson, K. Johnson, C. Juergens, I. Kassam, V. Lawlor, M. Lehman, S. Lehman, D. Leung, S. Mackay, M. MacKenzie, C. McCarthy, C. McIntosh, L. McKeon, H. Morrison, C. Mussap, J.-D. Myers, V. Nagalingam, G. Oldfield, V. O'May, J. Palmer, L. Parsons, K. Patching, T. Patching, V. Paul, M. Plotz, S. Preston, H. Rashad, M. Ratcliffe, S. Raynes, J. Rose, L. Sanders, M. Seremetkoska, H. Setio, S. Shone, P. Shrestha, C. Singh, C. Singleton, N. Stoyanov, S. Sutcliffe, K. Swaraj, J. Tarrant, S. Thompson, I.M. Tsay, M. Vorster, A. Waldman, L. Wallis, E. Wilford, K. Wong, S.J. Connolly, A. Spyropoulos, J. Eikelboom, R. Luton, M. Gupta, A.S. Pandey, S. Cheung, R. Leader, P. Beaudry, F. Ayala-Paredes, J. Berlingieri, J. Heath, G. Poirier, M. Du Preez, R. Nadeau, G. Dresser, R. Dhillon, T. Hruczkowski, B. Schweitzer, B. Coutu, P. Angaran, P. MacDonald, S. Vizel, S. Fikry, R. Parkash, A. Lavoie, J. Cha, B. Ramjattan, J. Bonet, K. Ahmad, L. Aro, T. Aves, K. Beaudry, C. Bergeron, J. Bigcanoe, N. Bignell, L. Breakwell, E. Burke, L. Carroll, B. Clarke, T. Cleveland, S. Daheb, P. Dehghani, I. Denis, Z. Djaidani, P. Dorian, S. Douglass, J. Dunnigan, A. Ewert, D. Farquhar, A. Fearon, L. Ferleyko, D. Fournier, B. Fox, M.-C. Grenier, W. Gulliver, K. Haveman, C. Hines, K. Hines, A.M. Jackson, C. Jean, G. Jethoo, R. Kahlon, S. Kelly, R. Kim, V. Korley, J. Kornder, L. Kwan, J. Largy, C. Lewis, S. Lewis, I. Mangat, R. Moor, J. Navratil, I. Neas, J. Otis, R. Otis, M. Pandey, F. Petrie, A. Pinter, M. Raines, P. Roberts, M. Robinson, G. Sas, S. Schulman, L. Snell, S. Spearson, J. Stevenson, T. Trahey, S. Wong, D. Wright, H. Ragy, A. Abd El-Aziz, S.K. Abou Seif, M.G. El Din, S. El Etriby, A. Elbahry, A. El-Etreby, M. Elkhadem, A. Katta, T. Khairy, A. Mowafy, M. Nawar, A. Ohanissian, A. Reda, M. Reda, H. Salem, N. Sami, S. Samir, M. Setiha, M. Sobhy, A. Soliman, N. Taha, M. Tawfik, E. Zaatout, D. Kettles, J. Bayat, H. Siebert, A. Horak, Y. Kelfkens, R. Garda, T. Pillay, M. Guerra, L. van Zyl, H. Theron, A. Murray, R. Louw, D. Greyling, P. Mntla, V. Ueckermann, R. Loghdey, S. Ismail, F. Ahmed, J. Engelbrecht, A. Ramdass, S. Maharajh, W. Oosthuysen, G. Angel, C. Bester, M. Booysen, C. Boshoff, C. Cannon, S. Cassimjee, C. Chami, G. Conway, A. Davids, L. de Meyer, G. Du Plessis, T. Ellis, L. Henley, M. Karsten, E. Loyd, J. Marks, L. Mavhusa, M. Mostert, A. Page, L. Rikhotso, M. Salie, J. Sasto, F. Shaik, A. Skein, L. Smith, G. Tarr, T. Tau, F. van Zyl, W. Al Mahmeed, G. Yousef, A. Agrawal, M. Nathani, M. Ibrahim, E.M. Esheiba, R. Singh, A. Naguib, M. Abu-Mahfouz, M. Al Omairi, A. Al Naeemi, R. Maruthanayagam, N. Bazargani, A. Wassef, R. Gupta, M. Khan, B. Subbaraman, A. Abdul, A. Al Mulla, S. El Bardisy, P. Haridas, S. Jadhav, K. Magdaluyo, M. Makdad, I. Maqsood, R. Mohamed, N. Sharma, R. Sharma, M. Thanzeel, S.Z. Goldhaber, R. Canosa, P. Rama, E. Blumberg, J. Garcia, P. Mullen, V. Wilson, A. Quick, K. Ferrick, W.M. Kutayli, M. Cox, M. Franco, S. Falkowski, R. Mendelson, M. Williams, S. Miller, S. Beach, A. Alfieri, T. Gutowski, I. Haque, R. Reddy, W. Ahmed, P. Delafontaine, D. Diercks, D. Theodoro, K. Remmel, M. Alberts, R. Ison, H. Noveck, P. Duffy, S. Pitta, D. Nishijima, C. Treasure, N. Asafu-Adjaye, K. Ball, M. Bartlett, M. Bentley, S. Bowers, A. Brown, A. Browne, J. Cameron-Watts, M. Canova, D. Cassidy, K. Cervellione, S. Congal, J. DePauw, A. Dickerson, M. Eley, L. Evans, S. Felpel, K. Ferdinand, D. Fielder, P. Gentry, A. Haideri, F. Hakimi, T. Harbour, E. Hartranft, B. Hawkins, M. Headlee, L. Henson, C. Herrick, T. Hicks, S. Jasinski, A. Jones, L. Jones, P. Jones, S. Karl, M. Keeling, J. Kerr, P. Knowles, J. Langdon, M. Lay, J.A. Lee, T. Lincoln, E. Malone, A. Merliss, D. Merritt, J. Minardo, B. Mooso, C. Orosco, V. Palumbo, M. Parker, T. Parrott, S. Paserchia, G. Pearl, J. Peterson, N. Pickelsimer, T. Purcell, J. Raynor, S. Raziano, C. Richard, T. Richardson, C. Robertson, A. Sage, T. Sanghera, P. Shaw, J. Shoemaker, K. Smith, B. Stephanie, A. Thatcher, H. Theobald, N. Thompson, L. Treasure, T. Tripti, C. Verdi, and V. Worthy

Subjects
Surgery, RD1-811, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background: The Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. Methods and results: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012–2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P

Published
2018
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17. Posterior reversible encephalopathy syndrome and COVID-19: A series of 6 cases from Lombardy, Italy

Author

Antonio Colombo, Filippo Martinelli Boneschi, Sandro Beretta, Nereo Bresolin, Maurizio Versino, Lorenzo Lorusso, Diego Spagnoli, Giulia Nastasi, Davide Vallauri, Stefania Rota, Maria Repaci, Massimo Ferrarini, Mattia Pozzato, Lucia Princiotta Cariddi, Payam Tabaee Damavandi, Federico Carimati, Paola Banfi, Alessandro Clemenzi, Margherita Marelli, Andrea Giorgianni, Gabriele Vinacci, Marco Mauri, Paola Melzi, Maria Di Stefano, Antonio Tetto, Margherita Canesi, and Andrea Salmaggi

Subjects
COVID-19, PRES, Seizures, Neurology. Diseases of the nervous system, RC346-429
Abstract

Posterior reversible encephalopathy cases are increasingly being reported in patients affected by COVID-19, but the largest series so far only includes 4 patients. We present a series of 6 patients diagnosed with PRES during COVID-19 hospitalized in 5 Centers in Lombardia, Italy. 5 out of the 6 patients required intensive care assistence and seizures developed at weaning from assisted ventilation. 3 out of 6 patients underwent cerebrospinal fluid analysis which was normal in all cases, with negative PCR for Sars-CoV-2 genome search. PRES occurrence may be less rare than supposed in COVID-19 patients and a high suspicion index is warranted for prompt diagnosis and treatment.

Published
2021
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18. Optical wavelength dependence of photoacoustic signal of gold nanofluid

Author

Marco Gandolfi, Francesco Banfi, and Christ Glorieux

Subjects
Photoacoustic effect, Heat transfer, Absorption coefficient, Non-linearity, Kapitza resistance, Nanoparticles, Physics, QC1-999, Acoustics. Sound, QC221-246, Optics. Light, QC350-467
Abstract

We investigate the optical wavelength dependence of the photoacoustic (PA) signal, detected with bandwidth (BW) in the MHz range, of gold nanospheres (NSs) immersed in water upon illumination with ns laser pulses. We compare the wavelength dependence of the PA signal (within the MHz BW) with the one of the optical absorption coefficient as determined from optical transmission measurements. Thermal boundary conductance (TBC) at the gold-water interface is taken into account, as well as the temperature dependence of the thermal expansion coefficient of water. The effects of NS size and laser pulse duration on the PA signal are also explored. The PA signal is investigated with an opto-thermo-acoustic model considering light absorption in gold NS and in a surrounding water shell.

Published
2020
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19. Mild form of Zellweger Spectrum Disorders (ZSD) due to variants in PEX1: Detailed clinical investigation in a 9-years-old female

Author

Maria Rosaria Barillari, Marianthi Karali, Valentina Di Iorio, Maria Contaldo, Vincenzo Piccolo, Maria Esposito, Giuseppe Costa, Giuseppe Argenziano, Rosario Serpico, Marco Carotenuto, Gerarda Cappuccio, Sandro Banfi, Paolo Melillo, and Francesca Simonelli

Subjects
Sensorineural hearing loss, Retinitis pigmentosa, Enamel defects, PEX genes, Peroxisomal biogenesis disorders, Mild Zellweger syndrome, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Peroxisomal biogenesis disorders (PBD) are rare autosomal recessive disorders with various degrees of severity caused by hypomorphic mutations in 13 different peroxin (PEX) genes. In this study, we report the clinical and molecular characterization of a 9-years-old female presenting an apparently isolated pre-lingual sensorineural hearing loss (SNHL) and early onset Retinitis Pigmentosa (RP) that may clinically overlap with Usher syndrome. Genetic testing by clinical exome sequencing identified two variants in PEX1: the missense variant c.274G > C; p.(Val92Leu) that was already reported in a PBD patient, and the variant c.2140_2145dup; p.(Ser714_Gln715dup) which is a novel, non-frameshift variant, absent in control databases. On the basis of the molecular analysis, a thorough clinical examination revealed nail and dental abnormalities, a mild cognitive impairment, learning disabilities and poor feeding, apart from the retinal and audiological features initially identified. The clinical and molecular findings led us to the diagnosis of a mild form of PBD. This study further emphasizes that mild forms of PBD can be a differential diagnosis of Usher syndrome and suggests that patients with mild cognitive impairment associated to visual and hearing loss should perform a comprehensive mutation screening that includes PEX genes.

Published
2020
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21. A functional limitation to the lower limbs affects the neural bases of motor imagery of gait

Author

Lucia Maria Sacheli, Laura Zapparoli, Matteo Preti, Carlo De Santis, Catia Pelosi, Nicola Ursino, Alberto Zerbi, Elena Stucovitz, Giuseppe Banfi, and Eraldo Paulesu

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract

Studies on athletes or neurological patients with motor disorders have shown a close link between motor experience and motor imagery skills. Here we evaluated whether a functional limitation due to a musculoskeletal disorder has an impact on the ability to mentally rehearse the motor patterns of walking, an overlearned and highly automatic behaviour. We assessed the behavioural performance (measured through mental chronometry tasks) and the neural signatures of motor imagery of gait in patients with chronic knee arthrosis and in age-matched, healthy controls. During fMRI, participants observed (i) stationary or (ii) moving videos of a path in a park shown in the first-person perspective: they were asked to imagine themselves (i) standing on or (ii) walking along the path, as if the camera were “their own eyes” (gait imagery (GI) task). In half of the trials, participants performed a dynamic gait imagery (DGI) task by combining foot movements with GI. Behavioural tests revealed a lower degree of isochrony between imagined and performed walking in the patients, indicating impairment in the ability to mentally rehearse gait motor patterns. Moreover, fMRI showed widespread hypoactivation during GI in motor planning (premotor and parietal) brain regions, the brainstem, and the cerebellum. Crucially, the performance of DGI had a modulatory effect on the patients and enhanced activation of the posterior parietal, brainstem, and cerebellar regions that the healthy controls recruited during the GI task. These findings show that functional limitations of peripheral origin may impact on gait motor representations, providing a rationale for cognitive rehabilitation protocols in patients with gait disorders of orthopaedic nature. The DGI task may be a suitable tool in this respect. Keywords: Gait, Orthopaedic patients, Motor imagery, fMRI

Published
2018
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22. A novel nonsense ATP7A pathogenic variant in a family exhibiting a variable occipital horn syndrome phenotype

Author

Maria Teresa Bonati, Federico Verde, Uros Hladnik, Paola Cattelan, Luca Campana, Chiara Castronovo, Nicola Ticozzi, Luca Maderna, Claudia Colombrita, Sergio Papa, Paolo Banfi, and Vincenzo Silani

Subjects
Copper transport, Continuum spectrum disorders, ATP7A late truncation, Limited elbow and shoulder movement, Weak grip, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

We report on a family with occipital horn syndrome (OHS) diagnosed in the proband's late fifties. A novel ATP7A pathogenic variant (c.4222A>T, p.(Lys1408*)), representing the first nonsense variant and the second late truncation causing OHS rather than classic Menkes disease, was found to segregate in the family. The predicted maintenance of transmembrane domains is consistent with a residual protein activity, which may explain the mild clinical presentation.

Published
2017
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23. ANGPTL8 requires ANGPTL3 to inhibit lipoprotein lipase and plasma triglyceride clearance[S]

Author

Jorge F. Haller, Ivory J. Mintah, Lisa M. Shihanian, Panayiotis Stevis, David Buckler, Corey A. Alexa-Braun, Sandra Kleiner, Serena Banfi, Jonathan C. Cohen, Helen H. Hobbs, George D. Yancopoulos, Andrew J. Murphy, Viktoria Gusarova, and Jesper Gromada

Subjects
angiopoietin-like 8, angiopoietin-like 3, blocking antibody, Biochemistry, QD415-436
Abstract

Angiopoietin-like (ANGPTL)3 and ANGPTL8 are secreted proteins and inhibitors of LPL-mediated plasma triglyceride (TG) clearance. It is unclear how these two ANGPTL proteins interact to regulate LPL activity. ANGPTL3 inhibits LPL activity and increases serum TG independent of ANGPTL8. These effects are reversed with an ANGPTL3 blocking antibody. Here, we show that ANGPTL8, although it possesses a functional inhibitory motif, is inactive by itself and requires ANGPTL3 expression to inhibit LPL and increase plasma TG. Using a mutated form of ANGPTL3 that lacks LPL inhibitory activity, we demonstrate that ANGPTL3 activity is not required for its ability to activate ANGPTL8. Moreover, coexpression of ANGPTL3 and ANGPTL8 leads to a far more efficacious increase in TG in mice than ANGPTL3 alone, suggesting the major inhibitory activity of this complex derives from ANGPTL8. An antibody to the C terminus of ANGPTL8 reversed LPL inhibition by ANGPTL8 in the presence of ANGPTL3. The antibody did not disrupt the ANGPTL8:ANGPTL3 complex, but came in close proximity to the LPL inhibitory motif in the N terminus of ANGPTL8. Collectively, these data show that ANGPTL8 has a functional LPL inhibitory motif, but only inhibits LPL and increases plasma TG levels in mice in the presence of ANGPTL3.

Published
2017
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24. Dataset of mRNA levels for dopaminergic receptors, adrenoceptors and tyrosine hydroxylase in lymphocytes from subjects with clinically isolated syndromes

Author

Marco Cosentino, Mauro Zaffaroni, Massimiliano Legnaro, Raffaella Bombelli, Laura Schembri, Damiano Baroncini, Anna Bianchi, Raffaella Clerici, Mario Guidotti, Paola Banfi, Giorgio Bono, and Franca Marino

Subjects
Clinically isolated syndrome, Multiple sclerosis, mRNA levels, Dopaminergic receptors, Adrenoceptors, Peripheral blood mononuclear cells, CD4+ T effector lymphocytes, CD4+ T regulatory lymphocytes, Computer applications to medicine. Medical informatics, R858-859.7, Science (General), Q1-390
Abstract

This data article presents a dataset of mRNA levels for dopaminergic receptors, adrenoceptors and for tyrosine hydoxylase, the rate-limiting enzyme in the synthesis of catecholamines, in peripheral blood mononuclear cells as well as in CD4+ T effector and regulatory cells from subjects with clinically isolated syndromes (CIS), which is a first episode of neurological disturbance(s) suggestive of multiple sclerosis. CIS subjects are divided into two groups according to their eventual progression, after 12 months from CIS, to clinically established multiple sclerosis. The data reported are related to the article entitled "Dopaminergic receptors and adrenoceptors in circulating lymphocytes as putative biomarkers for the early onset and progression of multiple sclerosis" (M. Cosentino, M. Zaffaroni, M. Legnaro, R. Bombelli, L. Schembri, D. Baroncini, A. Bianchi, R. Clerici, M. Guidotti, P. Banfi, G. Bono, F. Marino, 2016) [1].

Published
2016
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25. Lipoxidation in cardiovascular diseases

Author

Erica Gianazza, Maura Brioschi, Alma Martinez Fernandez, and Cristina Banfi

Subjects
Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Lipids can go through lipid peroxidation, an endogenous chain reaction that consists in the oxidative degradation of lipids leading to the generation of a wide variety of highly reactive carbonyl species (RCS), such as short-chain carbonyl derivatives and oxidized truncated phospholipids. RCS exert a wide range of biological effects due to their ability to interact and covalently bind to nucleophilic groups on other macromolecules, such as nucleic acids, phospholipids, and proteins, forming reversible and/or irreversible modifications and generating the so-called advanced lipoxidation end-products (ALEs).Lipoxidation plays a relevant role in the onset of cardiovascular diseases (CVD), mainly in the atherosclerosis-based diseases in which oxidized lipids and their adducts have been extensively characterized and associated with several processes responsible for the onset and development of atherosclerosis, such as endothelial dysfunction and inflammation.Herein we will review the current knowledge on the sources of lipids that undergo oxidation in the context of cardiovascular diseases, both from the bloodstream and tissues, and the methods for detection, characterization, and quantitation of their oxidative products and protein adducts.Moreover, lipoxidation and ALEs have been associated with many oxidative-based diseases, including CVD, not only as potential biomarkers but also as therapeutic targets. Indeed, several therapeutic strategies, acting at different levels of the ALEs cascade, have been proposed, essentially blocking ALEs formation, but also their catabolism or the resulting biological responses they induce. However, a deeper understanding of the mechanisms of formation and targets of ALEs could expand the available therapeutic strategies. Keywords: Lipoxidation, Mass spectrometry, Cardiovascular diseases, 4-Hydroxy-2-nonenal, Lipoprotein, Advanced lipoxidation end-products

Published
2019
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26. Thumbs up: Imagined hand movements counteract the adverse effects of post-surgical hand immobilization. Clinical, behavioral, and fMRI longitudinal observations

Author

Martina Gandola, Laura Zapparoli, Gianluca Saetta, Antonio De Santis, Alberto Zerbi, Giuseppe Banfi, Valerio Sansone, Maurilio Bruno, and Eraldo Paulesu

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract

Motor imagery (M.I.) training has been widely used to enhance motor behavior. To characterize the neural foundations of its rehabilitative effects in a pathological population we studied twenty-two patients with rhizarthrosis, a chronic degenerative articular disease in which thumb-to-fingers opposition becomes difficult due to increasing pain while the brain is typically intact. Before and after surgery, patients underwent behavioral tests to measure pain and motor performance and fMRI measurements of brain motor activity.After surgery, the affected hand was immobilized, and patients were enrolled in a M.I. training. The sample was split in those who had a high compliance with the program of scheduled exercises (T+, average compliance: 84%) and those with low compliance (T−, average compliance: 20%; cut-off point: 55%). We found that more intense M.I. training counteracts the adverse effects of immobilization reducing pain and expediting motor recovery. fMRI data from the post-surgery session showed that T+ patients had decreased brain activation in the premotor cortex and the supplementary motor area (SMA); meanwhile, for the same movements, the T− patients exhibited a reversed pattern. Furthermore, in the post-surgery fMRI session, pain intensity was correlated with activity in the ipsilateral precentral gyrus and, notably, in the insular cortex, a node of the pain matrix.These findings indicate that the motor simulations of M.I. have a facilitative effect on recovery by cortical plasticity mechanisms and optimization of motor control, thereby establishing the rationale for incorporating the systematic use of M.I. into standard rehabilitation for the management of post-immobilization syndromes characteristic of hand surgery. Keywords: Mental imagery training, Trapeziometacarpal joint osteoarthritis, Rhizarthrosis, Brain plasticity

Published
2019
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27. Effectiveness and safety of mouthpiece ventilation and nocturnal non-invasive ventilation in patients with kyphoscoliosis: Short and long-term outcomes after an episode of acute respiratory failure

Author

A. Nicolini, C. Barlascini, I.M.G. Piroddi, G. Garuti, and P.I. Banfi

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Background: Kyphoscoliosis is a skeletal condition involving the hyperflexion of the thoracic spine. It is characterized by reduced chest wall compliance and impaired respiratory mechanisms leading to progressive hypo-ventilation. We evaluated the effectiveness and the safety of non-invasive ventilation (NIV) in patients after an episode of acute respiratory failure (ARF). Methods: Eighteen patients with severe kyphoscoliosis who had been hospitalized for an episode of ARF were followed for 4 years. NIV was applied via mouthpiece (MPV) during the daytime and via mask during the night. The primary outcomes were changes in physiological and functional parameters as well as quality of life. Secondary outcomes were considered re-hospitalization and mortality rate after discharge. A set of control subjects was used for comparison. Results: All patients showed a significant improvement in several clinical, physiological, functional and quality of life parameters. Four of them (22.2%) died during the four year follow-up period. In the uni-variate analysis patients who died had higher cardiac co-morbidity, lower MIP and SNIP, higher paCO2, and oxygen desaturation index at initial admission. Conclusions: Diurnal MPV associated with nocturnal NIV had significantly improved lung function, clinical outcomes and quality of life. It should be considered as a safe alternative to traditional administering of NIV. Keywords: Kyphoscoliosis, Respiratory failure, Non-invasive ventilation, Mouthpiece ventilation

Published
2016
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28. Inactivation of ANGPTL3 reduces hepatic VLDL-triglyceride secretion1[S]

Author

Yan Wang, Viktoria Gusarova, Serena Banfi, Jesper Gromada, Jonathan C. Cohen, and Helen H. Hobbs

Subjects
cholesterol, dyslipidemias, lipase/endothelial, lipase/lipoprotein, angiopoietin-like protein 3, very low density lipoprotein, Biochemistry, QD415-436
Abstract

Humans and mice lacking angiopoietin-like protein 3 (ANGPTL3) have pan-hypolipidemia. ANGPTL3 inhibits two intravascular lipases, LPL and endothelial lipase, and the low plasma TG and HDL-cholesterol levels in ANGPTL3 deficiency reflect increased activity of these enzymes. The mechanism responsible for the low LDL-cholesterol levels associated with ANGPTL3 deficiency is not known. Here we used an anti-ANGPTL3 monoclonal antibody (REGN1500) to inactivate ANGPTL3 in mice with genetic deficiencies in key proteins involved in clearance of ApoB-containing lipoproteins. REGN1500 treatment consistently reduced plasma cholesterol levels in mice in which Apoe, Ldlr, Lrp1, and Sdc1 were inactivated singly or in combination, but did not alter clearance of rabbit 125I-βVLDL or mouse 125I-LDL. Despite a 61% reduction in VLDL-TG production, VLDL-ApoB-100 production was unchanged in REGN1500-treated animals. Hepatic TG content, fatty acid synthesis, and fatty acid oxidation were similar in REGN1500 and control antibody-treated animals. Taken together, our findings indicate that inactivation of ANGPTL3 does not affect the number of ApoB-containing lipoproteins secreted by the liver but alters the particles that are made such that they are cleared more rapidly from the circulation via a noncanonical pathway(s). The increased clearance of lipolytic remnants results in decreased production of LDL in ANGPTL3-deficient animals.

Published
2015
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29. Non-invasive ventilation in the treatment of sleep-related breathing disorders: A review and update

Author

A. Nicolini, P. Banfi, B. Grecchi, A. Lax, S. Walterspacher, C. Barlascini, and D. Robert

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Non-invasive mechanical ventilation (NIV) was originally used in patients with acute respiratory compromises or exacerbations of chronic respiratory diseases as an alternative to intubation. Over the last thirty years NIV has been used during the night in patients with stable chronic lung diseases such as obstructive sleep apnea, the overlap syndrome (COPD and obstructive sleep apnea), neuromuscular disorders, obesity-hypoventilation syndrome and in other conditions such as sleep disorders associated with congestive heart failure.In this review we discuss the different types of NIV, the specific conditions in which they can be used as well as the indications, recommendations, and evidence supporting the efficacy of NIV. Resumo: A ventilação mecânica não invasiva (VNI) foi originalmente usada em doentes com insuficiência respiratória aguda ou em exacerbações de doença respiratória crónica, como uma alternativa à intubação. Nos últimos trinta anos, a VNI tem sido usada durante a noite, em doentes com doenças pulmonares crónicas estáveis, como a apneia obstrutiva do sono, a síndrome de sobreposição (DPOC - doença pulmonar obstrutiva crónica - e apneia obstrutiva do sono), disfunções neuromusculares, síndrome de hipoventilação e obesidade, e em outras doenças como os distúrbios do sono associados a insuficiência cardíaca congestiva.Nesta análise discutimos os diferentes tipos de VNI, as condições específicas em que cada um deles pode ser usado, assim como as indicações, recomendações e a evidência que comprova a eficácia da VNI. Keywords: Sleep-related respiratory disorders, Non-invasive ventilation, Continuous positive airway pressure, Bi-level positive airway pressure, Palavras-chave: Distúrbios respiratórios do sono, Ventilação não invasiva, Pressão positiva contínua das vias aéreas, Pressão positiva em dois níveis nas vias aéreas

Published
2014
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30. Cardiomyogenesis is controlled by the miR-99a/let-7c cluster and epigenetic modifications

Author

Antonietta Coppola, Antonio Romito, Christelle Borel, Corinne Gehrig, Maryline Gagnebin, Emilie Falconnet, Antonella Izzo, Lucia Altucci, Sandro Banfi, Stylianos E. Antonarakis, Gabriella Minchiotti, and Gilda Cobellis

Subjects
Biology (General), QH301-705.5
Abstract

Understanding the molecular basis of cardiomyocyte development is critical for understanding the pathogenesis of pre- and post-natal cardiac disease. MicroRNAs (miRNAs) are post-transcriptional modulators of gene expression that play an important role in many developmental processes. Here, we show that the miR-99a/let-7c cluster, mapping on human chromosome 21, is involved in the control of cardiomyogenesis by altering epigenetic factors. By perturbing miRNA expression in mouse embryonic stem cells, we find that let-7c promotes cardiomyogenesis by upregulating genes involved in mesoderm specification (T/Bra and Nodal) and cardiac differentiation (Mesp1, Nkx2.5 and Tbx5). The action of let-7c is restricted to the early phase of mesoderm formation at the expense of endoderm and its late activation redirects cells toward other mesodermal derivatives. The Polycomb complex group protein Ezh2 is a direct target of let-7c, which promotes cardiac differentiation by modifying the H3K27me3 marks from the promoters of crucial cardiac transcription factors (Nkx2.5, Mef2c, Tbx5). In contrast, miR-99a represses cardiac differentiation via the nucleosome-remodeling factor Smarca5, attenuating the Nodal/Smad2 signaling. We demonstrated that the identified targets are underexpressed in human Down syndrome fetal heart specimens. By perturbing the expression levels of these miRNAs in embryonic stem cells, we were able to demonstrate that these miRNAs control lineage- and stage-specific transcription factors, working in concert with chromatin modifiers to direct cardiomyogenesis.

Published
2014
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31. Data for proteomic analysis of Human monocyte-derived macrophages

Author

S. Eligini, M. Brioschi, S. Fiorelli, E. Tremoli, S. Colli, and C. Banfi

Subjects
Macrophages, Proteomics, Laser capture microdissection, Computer applications to medicine. Medical informatics, R858-859.7, Science (General), Q1-390
Abstract

This data article is referred to the research article entitled Human monocyte-derived macrophages are heterogeneous: proteomic profile of different phenotypes by Eligini et al. Eligini S., Brioschi M., Fiorelli S., Tremoli E., Banfi C., Colli S. Human monocyte-derived macrophages are heterogeneous: proteomic profile of different phenotypes. J. Proteomics 124, 2015, 112-123. Macrophages obtained in vitro from blood monocytes are largely used as surrogate model of tissue macrophages that are heterogeneous and not easy to obtain and handle. Under spontaneous differentiation in vitro, monocyte-derived macrophages (MDMs) display two dominant subsets (round and spindle) that show different transcriptional, antigenic, and functional profiles mimicking, at least in part, the heterogeneity of tissue macrophages. This article reports the nano-LC-MSE analysis of the proteome of round and spindle MDMs allowing a deeper comprehension of macrophage heterogeneity.

Published
2015
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32. Data for proteomic analysis of murine cardiomyocytic HL-1 cells treated with siRNA against tissue factor

Author

Maura Brioschi, Sabrina Lento, Simona Barcella, Md. Talat Nasim, Stefania Ghilardi, Silvia Stella Barbieri, Elena Tremoli, and Cristina Banfi

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Science (General), Q1-390
Abstract

This data article is related to the research article entitled Proteomics of Tissue Factor silencing in cardiomyocytic cells reveals a new role for this coagulation factor in splicing machinery control by Lento et al. [1]. Tissue Factor (TF) is a key player in the coagulation cascade, but it has additional functions ranging from angiogenesis, tumour invasion and, in the heart, the maintenance of the integrity of cardiac cells. This article reports the nano-LC–MSE analysis of the cardiomyocytic HL-1 cell line proteome and describes the results obtained from a Gene Ontology analysis of those proteins affected by TF-gene silencing.

Published
2015
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33. Activation of NF-kB and ERK1/2 after permanent focal ischemia is abolished by simvastatin treatment

Author

Luigi Sironi, Cristina Banfi, Maura Brioschi, Paolo Gelosa, Uliano Guerrini, Elena Nobili, Anita Gianella, Rodolfo Paoletti, Elena Tremoli, and Mauro Cimino

Subjects
Statin, Inflammation, Cerebral ischemia, Permanent middle cerebral artery occlusion, Transcription factor, MAP kinase, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

We investigated the effects of simvastatin treatment on the expression of IL-1beta and MCP-1, the activity of NF-kB, and the signaling pathways related to NF-kB activation in a rat model of permanent middle cerebral artery occlusion (pMCAO). IL-1beta and MCP-1 expression, determined using RT-PCR, was enhanced by pMCAO; this effect was inhibited by the administration of simvastatin before ischemia. Pre-treatment with simvastatin abolished the ischemia-induced activation of NF-kB observed in vehicle-treated animals. The evaluation of signal transduction pathways, including extracellular signal-regulated kinase (ERK1/2), SAPK/JNK 46/54 and p38, indicated that only ERK1/2 phosphorylation was enhanced by ischemia, and this activation was prevented by simvastatin. ERK1/2-inhibitor, U0126, reduced brain ischemia but not cytokine induction. These results provide evidence that the HMG-CoA reductase inhibitor induces its effect in the protection of ischemic brain damage with a more complex mechanism which also involve anti-inflammatory properties rather than simple inhibition of ERK1/2 signaling pathway.

Published
2006
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34. Linoleic acid enhances the secretion of plasminogen activator inhibitor type 1 by HepG2 cells

Author

C Banfi, P Risé, L Mussoni, C Galli, and E Tremoli

Subjects
Biochemistry, QD415-436
Abstract

This study was undertaken in order to assess whether triglycerides and/or their fatty acids directly influence the secretion of plasminogen activator inhibitor type 1 (PAI-1) in HepG2 cells. To this end, subconfluent HepG2 cells were incubated with triglyceride-rich particles (TGRP) isolated from Intralipid for 16 h, and PAI-1 levels were determined in conditioned medium using a specific ELISA. TGRP (1 to 6 mg triglycerides/ml) concentration-dependently increased PAI-1 secretion by cells, concomitantly with significant increases in intracellular triglyceride (TG) levels. Fatty acid analysis indicated that the incubation of cells with 3 mg of TG per ml of TGRP induced significant accumulation of 18:2 n-6 (linoleic acid, LA) and 18:3 n-3 (linolenic acid) reflecting the fatty acid composition at the added triglycerides. We then tested the comparative effects on PAI-1 secretion by HepG2 cells of LA and 18:1 n-9 (oleic acid, OA). LA, as a bovine serum albumin (BSA) complex, concentration-dependently (1 to 35 mumol/L) increased the secretion of PAI-1 by cells, whereas OA-BSA only minimally affected it at the highest concentration used (35 mumol/L). Incorporation of LA into cell pools, in the presence of increasing concentration of the FA in the medium, was studied by the use of a preparation containing [14C]LA. LA accumulated in all lipid classes including diacylglycerol, the incorporated LA being converted into arachidonic acid (AA) as assessed by HPLC radiochromatography of the fatty acid methyl esters. It is concluded that PAI-1 secretion in HepG2 cells is modulated by triacylglycerols and by linoleic acid and/or its metabolic products.

Published
1997
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36. Illness expectations predict the development of influenza-like symptoms over the winter season.

Author

Pagnini F, Cavalera C, Volpato E, and Banfi P

Subjects
Adolescent, Adult, Cohort Studies, Female, Healthy Volunteers, Humans, Male, Self Report, Young Adult, Health Knowledge, Attitudes, Practice, Influenza, Human psychology, Seasons
Abstract

Objective: This study explores the hypothesis that cognitive expectations of catching influenza-like symptoms increase the chances of developing the symptoms over the winter season., Design: Self-reported data from 247 healthy volunteers were obtained twice, before and after the winter season. In the first assessment, expectations about developing influenza-like symptoms in the incoming months were charted. This data was matched with a post-winter assessment of the actual development of the symptoms., Results: The odds of developing symptoms were highly associated with the expectations declared months before (OR = 1.776), and the association remained stable (OR = 1.453) even when accounting for previous influenza-like illnesses and the perception of general health. In contrast with previous findings, perceived stress was not associated with symptom development., Conclusions: These results support the hypothesis of a self-fulfilling prophecy mechanism related to influenza-like symptoms., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Published
2020
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37. Healthcare costs of COPD in Italian referral centres: a prospective study.

Author

Koleva D, Motterlini N, Banfi P, and Garattini L

Subjects
Adult, Aged, Aged, 80 and over, Female, Humans, Italy epidemiology, Male, Middle Aged, Prospective Studies, Pulmonary Disease, Chronic Obstructive drug therapy, Pulmonary Disease, Chronic Obstructive epidemiology, Referral and Consultation economics, State Medicine, Health Care Costs statistics & numerical data, Health Resources statistics & numerical data, Pulmonary Disease, Chronic Obstructive economics
Abstract

Background: This study estimated the healthcare resource utilisation and costs of chronic obstructive pulmonary disease (COPD) patients, staged by severity, in the Italian pneumology departments (PDs)., Methods: The project was a multi-centre observational study conducted in 11 Italian PDs throughout the country. A total of 268 patients were recruited and followed prospectively for 1 year. For the purpose of analysis, patients were divided into four groups according to the severity at onset: mild COPD (stage I)-postbronchodilator FEV1/FVC <70% and FEV1 >or=80% of predicted; moderate COPD (stage II)-postbronchodilator FEV1/FVC <70% and 50%

Published
2007
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38. Levodropropizine (LD) activity in allergic asthmatic patients, challenged with ultrasonically nebulized distilled water, metacholine and allergen-induced bronchospasm.

Author

Bossi R, Banfi P, Filipazzi V, Castelli C, and Braga PC

Subjects
Administration, Oral, Adolescent, Adult, Antitussive Agents administration & dosage, Antitussive Agents pharmacology, Bronchial Hyperreactivity prevention & control, Bronchial Provocation Tests, Cross-Over Studies, Double-Blind Method, Female, Humans, Male, Middle Aged, Nebulizers and Vaporizers, Placebos, Propylene Glycols administration & dosage, Propylene Glycols pharmacology, Ultrasonic Therapy, Water, Allergens, Antitussive Agents therapeutic use, Asthma prevention & control, Bronchial Spasm prevention & control, Hypersensitivity prevention & control, Methacholine Chloride, Propylene Glycols therapeutic use
Abstract

The antitussive compound Levodropropizine (LD) is active in animal bronchoconstriction induced by histamine and capsaicin and in man protects from bronchoconstriction induced by capsaicin. The primary objective of this study was to evaluate the mechanism of action of LD given at 60 mg t.i.d. as oral drops, for 8 days by means of specific bronchial challenges (allergens) and of aspecific challenges acting via different receptors and fibers (i.e. metacholine via cholinergic receptors and ultrasonically nebulized distilled water (UNDW) via histamine and neuropeptide release). The study design is randomized, double-blind, cross-over versus placebo in 30 allergic asthmatic patients. Baseline bronchial tone and bronchoconstrictor response to metacholine (MCh) were not modified by active treatment nor by placebo. On the contrary, in airway responsiveness to UNDW, the active treatment showed an antagonist effect against induced bronchoconstriction of 59% [activity ratio (AR) as antilog = 0.41; 95% confidence interval 0.35-0.54; p < or = 0.05] in comparison to no effect for placebo. Similarly, in airway responsiveness to specific allergen, active treatment antagonized the bronchoconstrictor effect of grass pollen by 83% and of various allergens (dermatophagoides and grass pollen) by 72%, i.e. AR of 0.17 (95% confidence interval 0.045-0.65; p < 0.01) and of 0.28 (95% confidence interval 0.07-1.04; p < 0.05), respectively. No antagonist effect was evident with placebo at all times. Besides inhibiting cough, LD is also partially effective in inhibiting bronchial hyperreactive response against specific allergen and UNDW bronchoconstriction. Hence, LD might act by partly inhibiting histamine and neuropeptide release.

Published
1994

39. Middle latency auditory evoked potentials improve the detection of abnormalities along auditory pathways in multiple sclerosis patients.

Author

Versino M, Bergamaschi R, Romani A, Banfi P, Callieco R, Citterio A, Gerosa E, and Cosi V

Subjects
Acoustic Stimulation, Adolescent, Adult, Electroencephalography, Female, Humans, Male, Middle Aged, Reaction Time physiology, Auditory Pathways physiopathology, Evoked Potentials, Auditory physiology, Multiple Sclerosis physiopathology
Abstract

Brain-stem and middle latency auditory evoked potentials (BAEPs and MLAEPs) have been studied in 34 multiple sclerosis (MS) patients. We were able to detect a central nervous system auditory pathway involvement in 17 (50%) of the patients: 38% by BAEPs alone (I-V inter-peak latency) and 47% by MLAEPs alone (Na and Pa peak latency). Five patients had abnormal MLAEPs with normal BAEPs whereas the opposite was detectable in only 1 patient. In addition, most MLAEP parameters in the MS group statistically differed from those obtained in the control group. Therefore, our results demonstrated that the auditory pathway impairment could frequently be located at a rostral level along the auditory radiation. In conclusion, even if only Na and Pa components were considered, MLAEPs succeeded in improving the sensitivity of the auditory evoked potential examination without increasing the false positive rate.

Published
1992
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40. Biological markers of oxidative stress in mitochondrial myopathies with progressive external ophthalmoplegia.

Author

Piccolo G, Banfi P, Azan G, Rizzuto R, Bisson R, Sandoná D, and Bellomo G

Subjects
Adult, Aged, Biomarkers blood, Blood Proteins analysis, Child, Chromosome Deletion, Cytochrome-c Oxidase Deficiency, DNA, Mitochondrial genetics, Female, Free Radicals, Glutathione blood, Humans, Male, Malondialdehyde blood, Middle Aged, Ophthalmoplegia genetics, Ophthalmoplegia pathology, Reference Values, Lipid Peroxides blood, Mitochondria, Muscle metabolism, Neuromuscular Diseases metabolism, Ophthalmoplegia metabolism
Abstract

According to experimental models suggesting that overproduction of oxygen free-radicals may occur when the electron transport in the respiratory chain is impaired, we searched for in vivo biological markers of oxidative stress in 11 patients affected by histologically proven mitochondrial myopathy with progressive external ophthalmoplegia (PEO) and partial cytochrome c oxidase deficiency in muscle fibres. Six of the patients carried large-scale deletions of mitochondrial DNA. Biochemical assays included the determination of plasma and erythrocyte reduced glutathione (GSH) concentration, plasma malondialdehyde, fluorescent adducts of aldehydes with plasma proteins, and serum level of lipid peroxides. In patients with PEO the mean values of lipid peroxides and of the fluorescent adducts of aldehydes with plasma proteins were significantly higher with respect to normal controls, while the mean values of plasma and erythrocyte GSH concentration were significantly lower. The reported data indicate an increase of lipid peroxidation indexes along with the reduction of one of the most important antioxidant systems and suggest the hypothesis that overproduction of reduced oxygen species might be an adjunctive cause of cell damage in mitochondrial myopathies and encephalomyopathies associated with defects of oxidative phosphorylation.

Published
1991
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41. Normal insulin receptors in mitochondrial myopathies with ophthalmoplegia.

Author

Piccolo G, Aschei M, Ricordi A, Banfi P, Lo Curto F, and Fratino P

Subjects
Adult, Diabetes Complications, Female, Glucose Tolerance Test, Humans, Male, Middle Aged, Mitochondria, Muscle pathology, Muscular Diseases complications, Muscular Diseases pathology, Diabetes Mellitus metabolism, Fibroblasts immunology, Leukocytes, Mononuclear immunology, Mitochondria, Muscle metabolism, Muscular Diseases metabolism, Ophthalmoplegia complications, Receptor, Insulin metabolism
Abstract

Seven patients with histologically proven mitochondrial myopathy with ophthalmoplegia (OMM), 6 of them nondiabetic, 1 affected by diabetes mellitus (DM), were submitted to a study of glucose tolerance and of insulin receptors on peripheral mononuclear cells and cultured skin fibroblasts. The diabetic patient, who had the typical features of the Kearns-Sayre syndrome (KSS) and deleted muscle mitochondrial DNA (mtDNA) presented a low insulin secretion rate under physiological stimuli (intravenous glucose and glucagon) whereas the insulin receptor parameters were found normal. The other patients showed a normal glucose tolerance and normal insulin receptors. Our data support the hypothesis that insulin receptors are not involved in the pathogenesis of DM associated with mitochondrial encephalomyopathies, in contrast to other neuromuscular inherited disorders. The clinical and biological features of DM presented by our KSS patient show normal insulin receptor parameters in spite of a defective insulin secretion, possibly depending on mitochondrial dysfunction.

Published
1989
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