60 results on '"Serena Monaco"'
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2. Elucidation of Spartina dimethylsulfoniopropionate synthesis genes enables engineering of stress tolerant plants
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Rocky D. Payet, Lorelei J. Bilham, Shah Md Tamim Kabir, Serena Monaco, Ash R. Norcott, Mellieha G. E. Allen, Xiao-Yu Zhu, Anthony J. Davy, Charles A. Brearley, Jonathan D. Todd, and J. Benjamin Miller more...
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Science - Abstract
Abstract The organosulfur compound dimethylsulfoniopropionate (DMSP) has key roles in stress protection, global carbon and sulfur cycling, chemotaxis, and is a major source of climate-active gases. Saltmarshes are global hotspots for DMSP cycling due to Spartina cordgrasses that produce exceptionally high concentrations of DMSP. Here, in Spartina anglica, we identify the plant genes that underpin high-level DMSP synthesis: methionine S-methyltransferase (MMT), S-methylmethionine decarboxylase (SDC) and DMSP-amine oxidase (DOX). Homologs of these enzymes are common in plants, but differences in expression and catalytic efficiency explain why S. anglica accumulates such high DMSP concentrations and other plants only accumulate low concentrations. Furthermore, DMSP accumulation in S. anglica is consistent with DMSP having a role in oxidative and osmotic stress protection. Importantly, administration of DMSP by root uptake or over-expression of Spartina DMSP synthesis genes confers plant tolerance to salinity and drought offering a route for future bioengineering for sustainable crop production. more...
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- 2024
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Catalog
3. Rational Design of Dual-Domain Binding Inhibitors for N‑Acetylgalactosamine Transferase 2 with Improved Selectivity over the T1 and T3 Isoforms
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Ismael Compañón, Collin J. Ballard, Erandi Lira-Navarrete, Tanausú Santos, Serena Monaco, Juan C. Muñoz-García, Ignacio Delso, Jesus Angulo, Thomas A. Gerken, Katrine T. Schjoldager, Henrik Clausen, Tomás Tejero, Pedro Merino, Francisco Corzana, Ramon Hurtado-Guerrero, and Mattia Ghirardello more...
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Chemistry ,QD1-999 - Published
- 2024
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4. Exploring the sequence-function space of microbial fucosidases
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Ana Martínez Gascueña, Haiyang Wu, Rui Wang, C. David Owen, Pedro J. Hernando, Serena Monaco, Matthew Penner, Ke Xing, Gwenaelle Le Gall, Richard Gardner, Didier Ndeh, Paulina A. Urbanowicz, Daniel I. R. Spencer, Martin Walsh, Jesus Angulo, and Nathalie Juge more...
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Chemistry ,QD1-999 - Abstract
Abstract Microbial α-l-fucosidases catalyse the hydrolysis of terminal α-l-fucosidic linkages and can perform transglycosylation reactions. Based on sequence identity, α-l-fucosidases are classified in glycoside hydrolases (GHs) families of the carbohydrate-active enzyme database. Here we explored the sequence-function space of GH29 fucosidases. Based on sequence similarity network (SSN) analyses, 15 GH29 α-l-fucosidases were selected for functional characterisation. HPAEC-PAD and LC-FD-MS/MS analyses revealed substrate and linkage specificities for α1,2, α1,3, α1,4 and α1,6 linked fucosylated oligosaccharides and glycoconjugates, consistent with their SSN clustering. The structural basis for the substrate specificity of GH29 fucosidase from Bifidobacterium asteroides towards α1,6 linkages and FA2G2 N-glycan was determined by X-ray crystallography and STD NMR. The capacity of GH29 fucosidases to carry out transfucosylation reactions with GlcNAc and 3FN as acceptors was evaluated by TLC combined with ESI–MS and NMR. These experimental data supported the use of SSN to further explore the GH29 sequence-function space through machine-learning models. Our lightweight protein language models could accurately allocate test sequences in their respective SSN clusters and assign 34,258 non-redundant GH29 sequences into SSN clusters. It is expected that the combination of these computational approaches will be used in the future for the identification of novel GHs with desired specificities. more...
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- 2024
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5. The human gut symbiont Ruminococcus gnavus shows specificity to blood group A antigen during mucin glycan foraging: Implication for niche colonisation in the gastrointestinal tract.
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Haiyang Wu, Emmanuelle H Crost, C David Owen, Wouter van Bakel, Ana Martínez Gascueña, Dimitrios Latousakis, Thomas Hicks, Samuel Walpole, Paulina A Urbanowicz, Didier Ndeh, Serena Monaco, Laura Sánchez Salom, Ryan Griffiths, Raven S Reynolds, Anna Colvile, Daniel I R Spencer, Martin Walsh, Jesus Angulo, and Nathalie Juge more...
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Biology (General) ,QH301-705.5 - Abstract
The human gut symbiont Ruminococcus gnavus displays strain-specific repertoires of glycoside hydrolases (GHs) contributing to its spatial location in the gut. Sequence similarity network analysis identified strain-specific differences in blood-group endo-β-1,4-galactosidase belonging to the GH98 family. We determined the substrate and linkage specificities of GH98 from R. gnavus ATCC 29149, RgGH98, against a range of defined oligosaccharides and glycoconjugates including mucin. We showed by HPAEC-PAD and LC-FD-MS/MS that RgGH98 is specific for blood group A tetrasaccharide type II (BgA II). Isothermal titration calorimetry (ITC) and saturation transfer difference (STD) NMR confirmed RgGH98 affinity for blood group A over blood group B and H antigens. The molecular basis of RgGH98 strict specificity was further investigated using a combination of glycan microarrays, site-directed mutagenesis, and X-ray crystallography. The crystal structures of RgGH98 in complex with BgA trisaccharide (BgAtri) and of RgGH98 E411A with BgA II revealed a dedicated hydrogen network of residues, which were shown by site-directed mutagenesis to be critical to the recognition of the BgA epitope. We demonstrated experimentally that RgGH98 is part of an operon of 10 genes that is overexpresssed in vitro when R. gnavus ATCC 29149 is grown on mucin as sole carbon source as shown by RNAseq analysis and RT-qPCR confirmed RgGH98 expression on BgA II growth. Using MALDI-ToF MS, we showed that RgGH98 releases BgAtri from mucin and that pretreatment of mucin with RgGH98 confered R. gnavus E1 the ability to grow, by enabling the E1 strain to metabolise BgAtri and access the underlying mucin glycan chain. These data further support that the GH repertoire of R. gnavus strains enable them to colonise different nutritional niches in the human gut and has potential applications in diagnostic and therapeutics against infection. more...
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- 2021
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6. Multifrequency STD NMR Unveils the Interactions of Antibiotics With Burkholderia multivorans Biofilm Exopolysaccharide
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Ridvan Nepravishta, Serena Monaco, Marco Distefano, Roberto Rizzo, Paola Cescutti, and Jesus Angulo
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STD NMR ,multifrequency STD NMR ,exopolysaccharides ,biofilms ,Burkholderia multivorans ,Biology (General) ,QH301-705.5 - Abstract
Biofilms confine bacterial cells within self-produced matrices, offering advantages such as protection from antibiotics and entrapment of nutrients. Polysaccharides are major components in these macromolecular assemblies, and their interactions with other chemicals are of high relevance for the benefits provided by the biofilm 3D molecular matrix. NMR is a powerful technique for the study and characterization of the interactions between molecules of biological relevance. In this study, we have applied multifrequency saturation transfer difference (STD) NMR and DOSY NMR approaches to elucidate the interactions between the exopolysaccharide produced by Burkholderia multivorans C1576 (EpolC1576) and the antibiotics kanamycin and ceftadizime. The NMR strategies presented here allowed for an extensive characterization at an atomic level of the mechanisms behind the implication of the EpolC1576 in the recalcitrance phenomena, which is the ability of bacteria in biofilms to survive in the presence of antibiotics. Our results suggest an active role for EpolC1576 in the recalcitrance mechanisms toward kanamycin and ceftadizime, though through two different mechanisms. more...
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- 2021
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7. Inter-Ligand STD NMR: An Efficient 1D NMR Approach to Probe Relative Orientation of Ligands in a Multi-Subsite Protein Binding Pocket
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Serena Monaco, Jonathan Ramírez-Cárdenas, Ana Teresa Carmona, Inmaculada Robina, and Jesus Angulo
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saturation transfer difference NMR ,multi-frequency STD NMR ,multi-subsite binding pockets ,protein-ligand interactions ,ligand-based NMR ,Fragment Based Drug Discovery ,Medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
In recent years, Saturation Transfer Difference NMR (STD NMR) has been proven to be a powerful and versatile ligand-based NMR technique to elucidate crucial aspects in the investigation of protein-ligand complexes. Novel STD NMR approaches relying on “multi-frequency” irradiation have enabled us to even elucidate specific ligand-amino acid interactions and explore the binding of fragments in previously unknown binding subsites. Exploring multi-subsite protein binding pockets is especially important in Fragment Based Drug Discovery (FBDD) to design leads of increased specificity and efficacy. We hereby propose a novel multi-frequency STD NMR approach based on direct irradiation of one of the ligands in a multi-ligand binding process, to probe the vicinity and explore the relative orientation of fragments in adjacent binding sub-sites, which we called Inter-Ligand STD NMR (IL-STD NMR). We proved its applicability on (i) a standard protein-ligand system commonly used for ligand-observed NMR benchmarking: Naproxen as bound to Bovine Serum Albumin, and (ii) the biologically relevant system of Cholera Toxin Subunit B and two inhibitors adjacently bound within the GM1 binding site. Relative to Inter-Ligand NOE (ILOE), the current state-of-the-art methodology to probe relative orientations of adjacent ligands, IL-STD NMR requires about one tenth of the experimental time and protein consumption, making it a competitive methodology with the potential to be applied in the pharmaceutical industries. more...
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- 2022
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8. Structural basis for arginine glycosylation of host substrates by bacterial effector proteins
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Jun Bae Park, Young Hun Kim, Youngki Yoo, Juyeon Kim, Sung-Hoon Jun, Jin Won Cho, Samir El Qaidi, Samuel Walpole, Serena Monaco, Ana A. García-García, Miaomiao Wu, Michael P. Hays, Ramon Hurtado-Guerrero, Jesus Angulo, Philip R. Hardwidge, Jeon-Soo Shin, and Hyun-Soo Cho more...
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Science - Abstract
The type III secretion system effectors NleB and SseK are glycosyltransferases (GT) that specifically glycosylate arginine residues. Here the authors provide insights into their mechanism by combining X-ray crystallography, NMR, enzyme kinetics measurements, molecular dynamics simulations and in vivo experiments and show that SseK/NleB enzymes are retaining GTs. more...
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- 2018
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9. Unravelling the specificity and mechanism of sialic acid recognition by the gut symbiont Ruminococcus gnavus
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C. David Owen, Louise E. Tailford, Serena Monaco, Tanja Šuligoj, Laura Vaux, Romane Lallement, Zahra Khedri, Hai Yu, Karine Lecointe, John Walshaw, Sandra Tribolo, Marc Horrex, Andrew Bell, Xi Chen, Gary L. Taylor, Ajit Varki, Jesus Angulo, and Nathalie Juge more...
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Science - Abstract
The mucus layer is an important physical niche within the gut which harbours a distinct microbial community. Here the authors show that specific carbohydrate-binding modules associated with bacterial carbohydrate-active enzymes are mucus adhesins that target regions of the distal colon rich in sialomucins. more...
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- 2017
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10. Hemorrhagic Transformation in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Time to Initiation of Oral Anticoagulant Therapy and Outcomes
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Maurizio Paciaroni, Fabio Bandini, Giancarlo Agnelli, Georgios Tsivgoulis, Shadi Yaghi, Karen L. Furie, Prasanna Tadi, Cecilia Becattini, Marialuisa Zedde, Azmil H. Abdul‐Rahim, Kennedy R. Lees, Andrea Alberti, Michele Venti, Monica Acciarresi, Cataldo D'Amore, Maria Giulia Mosconi, Ludovica Anna Cimini, Riccardo Altavilla, Giacomo Volpi, Paolo Bovi, Monica Carletti, Alberto Rigatelli, Manuel Cappellari, Jukka Putaala, Liisa Tomppo, Turgut Tatlisumak, Simona Marcheselli, Alessandro Pezzini, Loris Poli, Alessandro Padovani, Luca Masotti, Vieri Vannucchi, Sung‐Il Sohn, Gianni Lorenzini, Rossana Tassi, Francesca Guideri, Maurizio Acampa, Giuseppe Martini, George Ntaios, George Athanasakis, Konstantinos Makaritsis, Efstathia Karagkiozi, Konstantinos Vadikolias, Chrissoula Liantinioti, Maria Chondrogianni, Nicola Mumoli, Domenico Consoli, Franco Galati, Simona Sacco, Antonio Carolei, Cindy Tiseo, Francesco Corea, Walter Ageno, Marta Bellesini, Giovanna Colombo, Giorgio Silvestrelli, Alfonso Ciccone, Alessia Lanari, Umberto Scoditti, Licia Denti, Michelangelo Mancuso, Miriam Maccarrone, Leonardo Ulivi, Giovanni Orlandi, Nicola Giannini, Gino Gialdini, Tiziana Tassinari, Maria Luisa De Lodovici, Giorgio Bono, Christina Rueckert, Antonio Baldi, Sebastiano D'Anna, Danilo Toni, Federica Letteri, Martina Giuntini, Enrico Maria Lotti, Yuriy Flomin, Alessio Pieroni, Odysseas Kargiotis, Theodore Karapanayiotides, Serena Monaco, Mario Maimone Baronello, Laszló Csiba, Lilla Szabó, Alberto Chiti, Elisa Giorli, Massimo Del Sette, Davide Imberti, Dorjan Zabzuni, Boris Doronin, Vera Volodina, Patrik Michel, Peter Vanacker, Kristian Barlinn, Lars‐Peder Pallesen, Jessica Barlinn, Dirk Deleu, Gayane Melikyan, Faisal Ibrahim, Naveed Akhtar, Vanessa Gourbali, and Valeria Caso more...
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atrial fibrillation ,hemorrhagic transformation ,stroke ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation (HT). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT, (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT. Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3–8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0–6.0) of those without HT; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT. On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24–2.35). Conclusions In patients with HT, anticoagulation was initiated about 12 days later than patients without HT. This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability. more...
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- 2018
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11. Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non–Vitamin‐K Oral Anticoagulants (RAF‐NOACs) Study
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Maurizio Paciaroni, Giancarlo Agnelli, Nicola Falocci, Georgios Tsivgoulis, Kostantinos Vadikolias, Chrysoula Liantinioti, Maria Chondrogianni, Paolo Bovi, Monica Carletti, Manuel Cappellari, Marialuisa Zedde, George Ntaios, Efstathia Karagkiozi, George Athanasakis, Kostantinos Makaritsis, Giorgio Silvestrelli, Alessia Lanari, Alfonso Ciccone, Jukka Putaala, Liisa Tomppo, Turgut Tatlisumak, Azmil H. Abdul‐Rahim, Kennedy R. Lees, Andrea Alberti, Michele Venti, Monica Acciarresi, Cataldo D'Amore, Cecilia Becattini, Maria Giulia Mosconi, Ludovica Anna Cimini, Rossana Soloperto, Luca Masotti, Vieri Vannucchi, Gianni Lorenzini, Rossana Tassi, Francesca Guideri, Maurizio Acampa, Giuseppe Martini, Sung‐Il Sohn, Simona Marcheselli, Nicola Mumoli, Maria Luisa De Lodovici, Giorgio Bono, Karen L. Furie, Prasanna Tadi, Shadi Yaghi, Danilo Toni, Federica Letteri, Tiziana Tassinari, Odysseas Kargiotis, Enrico Maria Lotti, Yuriy Flomin, Michelangelo Mancuso, Miriam Maccarrone, Nicola Giannini, Fabio Bandini, Alessandro Pezzini, Loris Poli, Alessandro Padovani, Umberto Scoditti, Licia Denti, Domenico Consoli, Franco Galati, Simona Sacco, Antonio Carolei, Cindy Tiseo, Vanessa Gourbali, Giovanni Orlandi, Martina Giuntini, Alberto Chiti, Elisa Giorli, Gino Gialdini, Francesco Corea, Walter Ageno, Marta Bellesini, Giovanna Colombo, Serena Monaco, Mario Maimone Baronello, Theodore Karapanayiotides, and Valeria Caso more...
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acute stroke ,anticoagulants ,atrial fibrillation ,secondary prevention ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundThe optimal timing to administer non–vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational multicenter study evaluated the rates of early recurrence and major bleeding (within 90 days) and their timing in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention. Methods and ResultsRecurrence was defined as the composite of ischemic stroke, transient ischemic attack, and symptomatic systemic embolism, and major bleeding was defined as symptomatic cerebral and major extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%) were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with apixaban. Patients who received dabigatran were younger and had lower admission National Institutes of Health Stroke Scale score and less commonly had a CHA2DS2‐VASc score >4 and less reduced renal function. Thirty‐two patients (2.8%) had early recurrence, and 27 (2.4%) had major bleeding. The rates of early recurrence and major bleeding were, respectively, 1.8% and 0.5% in patients receiving dabigatran, 1.6% and 2.5% in those receiving rivaroxaban, and 4.0% and 2.9% in those receiving apixaban. Patients who initiated NOACs within 2 days after acute stroke had a composite rate of recurrence and major bleeding of 12.4%; composite rates were 2.1% for those who initiated NOACs between 3 and 14 days and 9.1% for those who initiated >14 days after acute stroke. ConclusionsIn patients with acute ischemic stroke and atrial fibrillation, treatment with NOACs was associated with a combined 5% rate of ischemic embolic recurrence and severe bleeding within 90 days. more...
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- 2017
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12. Unravelling the mechanisms of drugs partitioning phenomena in micellar systems via NMR spectroscopy
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Katarzyna Malec, Serena Monaco, Ignacio Delso, Justyna Nestorowicz, Marta Kozakiewicz-Latała, Bożena Karolewicz, Yaroslav Z. Khimyak, Jesús Angulo, and Karol P. Nartowski
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Biomaterials ,Colloid and Surface Chemistry ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials - Published
- 2023
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13. Practical '1-2-3-4-Day' Rule for Starting Direct Oral Anticoagulants After Ischemic Stroke With Atrial Fibrillation: Combined Hospital-Based Cohort Study
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Shunsuke Kimura, Kazunori Toyoda, Sohei Yoshimura, Kazuo Minematsu, Masahiro Yasaka, Maurizio Paciaroni, David J. Werring, Hiroshi Yamagami, Takehiko Nagao, Shinichi Yoshimura, Alexandros Polymeris, Annaelle Zietz, Stefan T. Engelter, Bernd Kallmünzer, Manuel Cappellari, Tetsuya Chiba, Takeshi Yoshimoto, Masayuki Shiozawa, Takanari Kitazono, Masatoshi Koga, Kenichi Todo, Kazumi Kimura, Yoshiki Yagita, Eisuke Furui, Ryo Itabashi, Tadashi Terasaki, Yoshiaki Shiokawa, Teruyuki Hirano, Kenji Kamiyama, Jyoji Nakagawara, Shunya Takizawa, Kazunari Homma, Satoshi Okuda, Yasushi Okada, Keisuke Tokunaga, Tomoaki Kameda, Kazuomi Kario, Yoshinari Nagakane, Yasuhiro Hasegawa, Hisanao Akiyama, Satoshi Shibuya, Hiroshi Mochizuki, Yasuhiro Ito, Takahiro Nakashima, Hideki Matsuoka, Kazuhiro Takamatsu, Kazutoshi Nishiyama, Shoichiro Sato, Shoji Arihiro, Manabu Inoue, Masahito Takagi, Kanta Tanaka, Kazuyuki Nagatsuka, Takenori Yamaguchi, Yoichiro Hashimoto, Kiyohiro Houkin, Kazuo Kitagawa, Masayasu Matsumoto, Norio Tanahashi, Yasuo Terayama, Shinichiro Uchiyama, Etsuro Mori, Yutaka Furukawa, Takeshi Kimura, Yoshiaki Kumon, Ken Nagata, Shigeru Nogawa, Tomohiro Sakamoto, Toshinori Hirai, Kohsuke Kudo, Makoto Sasaki, Shotai Kobayashi, Toshimitsu Hamasaki, Michela Giustozzi, Monica Acciarresi, Giancarlo Agnelli, Valeria Caso, Fabio Bandini, Georgios Tsivgoulis, Shadi Yaghi, Karen L. Furie, Prasanna Tadi, Cecilia Becattini, Marialuisa Zedde, Azmil H Abdul-Rahim, Kennedy R Lees, Andrea Alberti, Michele Venti, Cataldo D’Amore, Maria Giulia Mosconi, Ludovica Anna Cimini, Paolo Bovi, Monica Carletti, Alberto Rigatelli, Jukka Putaala, Liisa Tomppo, Turgut Tatlisumak, Simona Marcheselli, Alessandro Pezzini, Loris Poli, Alessandro Padovani, Vieri Vannucchi, Sung-Il Sohn, Gianni Lorenzini, Rossana Tassi, Francesca Guideri, Maurizio Acampa, Giuseppe Martini, George Ntaios, George Athanasakis, Konstantinos Makaritsis, Efstathia Karagkiozi, Konstantinos Vadikolias, Chrissoula Liantinioti, Maria Chondrogianni, Nicola Mumoli, Franco Galati, Simona Sacco, Cindy Tiseo, Francesco Corea, Walter Ageno, Marta Bellesini, Giovanna Colombo, Giorgio Silvestrelli, Alfonso Ciccone, Alessia Lanari, Umberto Scoditti, Licia Denti, Michelangelo Mancuso, Miriam Maccarrone, Leonardo Ulivi, Giovanni Orlandi, Nicola Giannini, Tiziana Tassinari, Maria Luisa De Lodovici, Christina Rueckert, Antonio Baldi, Danilo Toni, Federica Letteri, Martina Giuntini, Enrico Maria Lotti, Yuriy Flomin, Alessio Pieroni, Odysseas Kargiotis, Theodore Karapanayiotides, Serena Monaco, Mario Maimone Baronello, Laszló Csiba, Lilla Szabó, Alberto Chiti, Elisa Giorli, Massimo Del Sette, Davide Imberti, Dorjan Zabzuni, Boris Doronin, Vera Volodina, Patrik Michel, Peter Vanacker, Kristian Barlinn, Lars-Peder Pallesen, Jessica Barlinn, Dirk Deleu, Gayane Melikyan, Faisal Ibrahim, Naveed Akhtar, Vanessa Gourbali, Luca Masotti, Adrian Parry-Jones, Chris Patterson, Christopher Price, Abduelbaset Elmarimi, Anthea Parry, Arumug Nallasivam, Azlisham Mohd Nor, Bernard Esis, David Bruce, Christine Roffe, Clare Holmes, David Cohen, David Hargroves, David Mangion, Dinesh Chadha, Djamil Vahidassr, Dulka Manawadu, Elio Giallombardo, Elizabeth Warburton, Enrico Flossman, Gunaratam Gunathilagan, Harald Proschel, Hedley Emsley, Ijaz Anwar, James Okwera, Janet Putterill, Janice O’Connell, John Bamford, John Corrigan, Jon Scott, Jonathan Birns, Karen Kee, Kari Saastamoinen, Kath Pasco, Krishna Dani, Lakshmanan Sekaran, Lillian Choy, Liz Iveson, Maam Mamun, Mahmud Sajid, Martin Cooper, Matthew Burn, Matthew Smith, Michael Power, Michelle Davis, Nigel Smyth, Roland Veltkamp, Pankaj Sharma, Paul Guyler, Paul O’Mahony, Peter Wilkinson, Prabel Datta, Prasanna Aghoram, Rachel Marsh, Robert Luder, Sanjeevikumar Meenakishundaram, Santhosh Subramonian, Simon Leach, Sissi Ispoglou, Sreeman Andole, Timothy England, Aravindakshan Manoj, Frances Harrington, Habib Rehman, Jane Sword, Julie Staals, Karim Mahawish, Kirsty Harkness, Louise Shaw, Michael McCormich, Nikola Sprigg, Syed Mansoor, Vinodh Krishnamurthy, Philippe A Lyrer, Leo H Bonati, David J Seiffge, Christopher Traenka, Nils Peters, Gian Marco De Marchis, Sebastian Thilemann, Nikolaos S Avramiotis, Henrik Gensicke, Lisa Hert, Benjamin Wagner, Fabian Schaub, Louisa Meya, Joachim Fladt, Tolga Dittrich, Urs Fisch, Bruno Bonetti, Giampaolo Tomelleri, Nicola Micheletti, Cecilia Zivelonghi, Andrea Emiliani, Kosmas Macha, Gabriela Siedler, Svenja Stoll, Ruihao Wang, Bastian Volbers, Stefan Schwab, David Haupenthal, and Luise Gaßmann more...
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Advanced and Specialized Nursing ,acute ischemic stroke ,Time Factors ,Administration, Oral ,Anticoagulants ,Hemorrhage ,cardioembolism ,Hospitals ,United States ,Brain Ischemia ,anticoagulation ,atrial fibrillation ,stroke prevention ,Cohort Studies ,Stroke ,Treatment Outcome ,Ischemic Attack, Transient ,Atrial Fibrillation ,Humans ,Prospective Studies ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,Ischemic Stroke - Abstract
Background: The “1-3-6-12-day rule” for starting direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation after acute ischemic stroke or transient ischemic attack recommends timings that may be later than used in clinical practice. We investigated more practical optimal timing of DOAC initiation according to stroke severity. Methods: The combined data of prospective registries in Japan, Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-nonvalvular atrial fibrillation (September 2011 to March 2014) and RELAXED (February 2014 to April 2016) were used. Patients were divided into transient ischemic attack and 3 stroke subgroups by the National Institutes of Health Stroke Scale score: mild (0–7), moderate (8–15), and severe (≥16). The early treatment group was defined as patients starting DOACs earlier than the median initiation day in each subgroup. Outcomes included a composite of recurrent stroke or systemic embolism, ischemic stroke, and severe bleeding within 90 days. Six European prospective registries were used for validation. Results: In the 1797 derivation cohort patients, DOACs were started at median 2 days after transient ischemic attack and 3, 4, and 5 days after mild, moderate, and severe strokes, respectively. Stroke or systemic embolism was less common in Early Group (n=785)—initiating DOACS within 1, 2, 3, and 4 days, respectively—than Late Group (n=1012) (1.9% versus 3.9%; adjusted hazard ratio, 0.50 [95% CI, 0.27–0.89]), as was ischemic stroke (1.7% versus 3.2%, 0.54 [0.27–0.999]). Major bleeding was similarly common in the 2 groups (0.8% versus 1.0%). On validation, both ischemic stroke (2.4% versus 2.2%) and intracranial hemorrhage (0.2% versus 0.6%) were similarly common in Early (n=547) and Late (n=1483) Groups defined using derivation data. Conclusions: In Japanese and European populations, early DOAC initiation within 1, 2, 3, or 4 days according to stroke severity seemed to be feasible to decrease the risk of recurrent stroke or systemic embolism and no increase in major bleeding. These findings support ongoing randomized trials to better establish the optimal timing of DOAC initiation. more...
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- 2022
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14. Novel dimethylsulfoniopropionate biosynthesis enzymes in diverse marine bacteria, cyanobacteria and abundant algae
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Jinyan Wang, Shun Zhou, Andrew Curson, Ana Vieira, Keanu Walsham, Serena Monaco, Chun-Yang Li, Peter Paolo Rivera, Xiao-Di Wang, Libby Hanwell, Xiao-Yu Zhu, Pedro Leão, David J. Lea-Smith, Yuzhong Zhang, Xiaohua Zhang, and Jonathan Todd more...
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Dimethylsulfoniopropionate (DMSP) is an abundant marine organosulfur compound[1] with roles in stress protection[2, 3], chemotaxis[4], nutrient and sulfur cycling[5] and, potentially, climate regulation[6, 7]. Marine algae and bacteria are considered significant DMSP producers, but many diverse representatives lack known DMSP synthesis genes/enzymes[8, 9]. Here, new DMSP biosynthesis enzymes were identified that considerably increase the number and diversity of potential DMSP-producing organisms, inferring new and significant global DMSP producers. A novel bifunctional DMSP biosynthesis enzyme, DsyGD, identified in the rhizobacterium Gynuella sunshinyii, produces DMSP at levels higher than any other bacterium from methylthiohydroxybutyrate (MTHB) via an N-terminal MTHB S-methyltransferase domain (termed DsyG) and a C-terminal dimethylsulfoniohydroxybutyrate (DMSHB) decarboxylase domain (termed DsyD, which is the first reported enzyme with this activity). DsyGD is also found in some filamentous cyanobacteria, not previously known to produce DMSP. Regulation of DMSP production and dsyGD transcription was consistent with their role in osmoprotection. Indeed, cloned dsyGD conferred osmotolerance to bacteria deficient in osmolyte production, something not previously demonstrated for any known DMSP synthesis gene, and which could be exploited for biotechnology e.g., engineering salt tolerance. DsyGD characterisation led to identification of phylogenetically distinct DsyG-like proteins, termed DSYE, with MTHB S-methyltransferase activity, in diverse and environmentally abundant Chlorophyta, Chlorachniophyta, Ochraphyta, Haptophyta and Bacillariophyta algae. These algae comprise a mix of low, high and previously unknown DMSP producers[10]. Algae containing DSYE, particularly bloom-forming Pelagophyceae species, which we showed to accumulate medium-high intracellular DMSP levels, were globally more abundant DMSP producers than Haptophyta, Dinophyta and Bacillariophyta with DSYB and/or TpMMT. This highlights the potential importance of Pelagophyceae and other DSYE containing algae in global DMSP production and sulfur cycling. more...
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- 2023
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15. Function and wide distribution of DMSOP cleaving enzymes in marine organisms
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Ornella Carrion, Chun-Yang Li, Ming Peng, Jinyan Wang, Georg Pohnert, Muhaiminatul Azizah, Xiao-Yu Zhu, Andrew Curson, Keanu Walsham, Xiaohua Zhang, Serena Monaco, James Harvey, Qing Wang, Xiu-Lan Chen, Chao Gao, Ning Wang, Xiu-Juan Wang, Peng Wang, Stephen Giovannoni, Chih-Ping Lee, Christopher Suffridge, Yu Zhang, Ziqi Luo, Dazhi Wang, Jonathan Todd, and Yuzhong Zhang more...
- Abstract
Dimethylsulfoxonium propionate (DMSOP) is a recently identified and abundant marine organosulfur compound with purported roles in oxidative stress protection, global carbon and sulfur cycling1. Diverse algae and bacteria synthesise DMSOP from dimethylsulfoniopropionate (DMSP), which potentially limits the production of climate-active gases e.g., dimethylsulfide (DMS) generated from microbial DMSP cleavage1. Here, DMSOP was found at mM levels in saltmarsh sediment, >10-fold higher than DMSP, and orders of magnitude higher than DMSOP levels previously reported in seawater1. Moreover, we showed bacteria could utilise DMSOP as an osmoprotectant. Some bacteria also cleave DMSOP liberating dimethyl sulfoxide (DMSO), an ubiquitous marine metabolite and acrylate1, but the enzymes responsible and their environmental importance were unknown. Here, we elucidated the DMSOP cleavage mechanism/s in diverse heterotrophic bacteria, e.g., SAR11 clade and Roseobacters, and fungi and phototrophic algae, e.g., Emiliania huxleyi, not previously known to have this activity. All these diverse organisms utilised their DMSP lyase ‘Ddd’ or ‘Alma1’ enzymes, that span five protein families, to cleave DMSOP with similar specific activities to DMSP. Bacteria with DMSP lyases that used DMSP as a carbon source likewise used DMSOP. Furthermore, ddd gene transcription in these bacteria was induced by DMSOP, including dddK in SAR11 strain HTCC1062. We determined the structure of DddK bound to DMSOP and concluded that the catalytic mechanisms of DMSOP cleavage by Ddd enzymes were like those for DMSP. Given the predicted teragram DMSOP production budget1, its newly found abundance in marine sediments, and the abundance of microbial DMSP lyase genes and transcripts in marine environments, DMSOP cleavage is likely a globally significant process influencing global carbon and sulfur fluxes and marine ecological interactions. more...
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- 2023
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16. Unravelling the mechanisms of small molecules partitioning phenomena in micellar systems via multifrequency-STD NMR NMR spectroscopy
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Katarzyna Malec, Serena Monaco, Ignacio Delso, Justyna Nestorowicz, Marta Kozakiewicz-Latała, Bozena Karolewicz, Yaroslav Khimyak, Jesús Angulo, and Karol Nartowski
- Abstract
Despite extensive use of micelles in materials and colloidal science, their supramolecular organization as well as host-guest interactions within these dynamic assemblies are poorly understood. Small guest molecules in the presence of micelles undergo constant exchange between a micellar aggregate and the surrounding solution, posing a considerable challenge for their molecular level characterisation. In this work we reveal the interaction maps between small guest molecules and surfactants forming micelles via novel applications of NMR techniques supported with state-of-the-art analytical methods used in colloidal science. Model micelles composed of structurally distinct surfactants (block non-ionic polymer Pluronic® F-127, non-ionic surfactant Tween 20 or Tween 80 and ionic surfactant SLS, sodium lauryl sulphate) were selected and loaded with model small molecules of biochemical relevance (i.e. the drugs fluconazole, FLU or indomethacin, IMC) known to have different partition coefficients. Molecular level organization of FLU or IMC within hydrophilic and hydrophobic domains of micellar aggregates was established using combination of NMR methods (1D 1H NMR, 1D 19F NMR, 2D 1H-1H NOESY and 2D 1H-19F HOESY, and the multifrequency-STD NMR) and corroborated with molecular dynamics (MD) simulations. This is the first application of multifrequency-STD NMR to colloidal systems, enabling us to elucidate intricately detailed patterns of drug/micelle interactions in a single NMR experiment within minutes. Importantly, our results indicate that flexible surfactants, such as block copolymers and polysorbates, form micellar aggregates with a surface composed of both hydrophilic and hydrophobic domains and do not follow the classical core-shell model of the micelle. We propose that the magnitude of the changes in 1H chemical shifts corroborated with interaction maps obtained from DEEP-STD NMR and 2D NMR experiments can be used as an indicator of the strength of the guest-surfactant interactions. This NMR toolbox can be adopted for the analysis of broad range colloidal host-guest systems from soft materials to biological systems. more...
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- 2022
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17. Risk Factors for Intracerebral Hemorrhage in Patients With Atrial Fibrillation on Non–Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention
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Panagiotis Halvatsiotis, Giuseppe Reale, Jennifer A. Frontera, Giuseppe Martini, S. Pegoraro, Leonardo Pantoni, Aristeidis H. Katsanos, Piergiorgio Lochner, Daniel Strbian, Giorgia Zepponi, Valentina Saia, Karen L. Furie, Giancarlo Agnelli, Elisa Giorli, Erica Scher, Lina Palaiodimou, Valentina Arnao, Giorgio Silvestrelli, Simona Marcheselli, Letizia Riva, Andrea Zini, Angela Risitano, Tiziana Tassinari, Carlo Emanuele Saggese, Francesco Palmerini, Erika Schirinzi, Michael E. Reznik, Marina Mannino, Jukka Putaala, Maria Kosmidou, Michela Giustozzi, Cesare Porta, Maurizio Paciaroni, Marina Padroni, Loris Poli, Maria Cristina Vedovati, Danilo Toni, Manuel Cappellari, Alessandro Rocco, Alessandro Pezzini, Ashkan Shoamanesh, Stefano Forlivesi, Serena Monaco, Raffaele Ornello, Simona Sacco, Silvia Rosa, Shadi Yaghi, Valeria Terruso, Andrea Alberti, Francesco Corea, Elena Ferrari, Christoph Stretz, Marialuisa Zedde, Monica Acciarresi, Cataldo D'Amore, Kateryna Antonenko, Nemanja Popovic, Francesca Guideri, Evangelos Ntais, Boris Doronin, Luca Masotti, Filippo Angelini, Giovanni Orlandi, Licia Denti, Nicola Mumoli, Sotirios Giannopoulos, Elisabetta Toso, Maria Giulia Mosconi, Paolo Aridon, Aurelia Zauli, Giuseppe Micieli, Azmil H. Abdul-Rahim, Laura Brancaleoni, Marina Diomedi, Elisa Grifoni, Georgios Tsivgoulis, Maurizio Acampa, Michele Venti, Walter Ageno, Pietro Caliandro, Alfonso Ciccone, Isabella Canavero, Laura Franco, George Ntaios, Fabio Bandini, Vera Volodina, Pierluigi Bertora, Dimitrios Sagris, Antonio Baldi, Michele Romoli, Hanne Sallinen, Michelangelo Mancuso, Yuriy Flomin, Rossana Tassi, Valeria Caso, Massimo Del Sette, Enrico Maria Lotti, Antonio Gasparro, Alberto Chiti, Jesse Dawson, Brian Mac Grory, Alberto Rigatelli, Paciaroni, Maurizio, Agnelli, Giancarlo, Giustozzi, Michela, Caso, Valeria, Toso, Elisabetta, Angelini, Filippo, Canavero, Isabella, Micieli, Giuseppe, Antonenko, Kateryna, Rocco, Alessandro, Diomedi, Marina, Katsanos, Aristeidis H, Shoamanesh, Ashkan, Giannopoulos, Sotirio, Ageno, Walter, Pegoraro, Samuela, Putaala, Jukka, Strbian, Daniel, Sallinen, Hanne, Mac Grory, Brian C, Furie, Karen L, Stretz, Christoph, Reznik, Michael E, Alberti, Andrea, Venti, Michele, Mosconi, Maria Giulia, Vedovati, Maria Cristina, Franco, Laura, Zepponi, Giorgia, Romoli, Michele, Zini, Andrea, Brancaleoni, Laura, Riva, Letizia, Silvestrelli, Giorgio, Ciccone, Alfonso, Zedde, Maria Luisa, Giorli, Elisa, Kosmidou, Maria, Ntais, Evangelo, Palaiodimou, Lina, Halvatsiotis, Panagioti, Tassinari, Tiziana, Saia, Valentina, Ornello, Raffaele, Sacco, Simona, Bandini, Fabio, Mancuso, Michelangelo, Orlandi, Giovanni, Ferrari, Elena, Pezzini, Alessandro, Poli, Lori, Cappellari, Manuel, Forlivesi, Stefano, Rigatelli, Alberto, Yaghi, Shadi, Scher, Erica, Frontera, Jennifer A, Masotti, Luca, Grifoni, Elisa, Caliandro, Pietro, Zauli, Aurelia, Reale, Giuseppe, Marcheselli, Simona, Gasparro, Antonio, Terruso, Valeria, Arnao, Valentina, Aridon, Paolo, Abdul-Rahim, Azmil H, Dawson, Jesse, Saggese, Carlo Emanuele, Palmerini, Francesco, Doronin, Bori, Volodina, Vera, Toni, Danilo, Risitano, Angela, Schirinzi, Erika, Del Sette, Massimo, Lochner, Piergiorgio, Monaco, Serena, Mannino, Marina, Tassi, Rossana, Guideri, Francesca, Acampa, Maurizio, Martini, Giuseppe, Lotti, Enrico Maria, Padroni, Marina, Pantoni, Leonardo, Rosa, Silvia, Bertora, Pierluigi, Ntaios, George, Sagris, Dimitrio, Baldi, Antonio, D'Amore, Cataldo, Mumoli, Nicola, Porta, Cesare, Denti, Licia, Chiti, Alberto, Corea, Francesco, Acciarresi, Monica, Flomin, Yuriy, Popovic, Nemanja, and Tsivgoulis, Georgios more...
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Male ,Administration, Oral ,030204 cardiovascular system & hematology ,Settore MED/11 ,0302 clinical medicine ,80 and over ,risk factors ,Medicine ,atrial fibrillation ,Prospective Studies ,Aged, 80 and over ,cerebral hemorrhage ,logistic models ,white matter ,Aged ,Antithrombins ,Atrial Fibrillation ,Case-Control Studies ,Cerebral Hemorrhage ,Female ,Humans ,Middle Aged ,Risk Factors ,Stroke ,Atrial fibrillation ,Vitamin K antagonist ,3. Good health ,Administration ,Settore MED/26 - Neurologia ,Cardiology and Cardiovascular Medicine ,medicine.drug ,Oral ,medicine.medical_specialty ,medicine.drug_class ,Settore MED/26 ,Lower risk ,03 medical and health sciences ,Internal medicine ,cardiovascular diseases ,logistic model ,Advanced and Specialized Nursing ,Intracerebral hemorrhage ,business.industry ,Warfarin ,medicine.disease ,Clinical trial ,Concomitant ,Heart failure ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Background and Purpose: Clinical trials on stroke prevention in patients with atrial fibrillation have consistently shown clinical benefit from either warfarin or non–vitamin K antagonist oral anticoagulants (NOACs). NOAC-treated patients have consistently reported to be at lower risk for intracerebral hemorrhage (ICH) than warfarin-treated patients. The aims of this prospective, multicenter, multinational, unmatched, case-control study were (1) to investigate for risk factors that could predict ICH occurring in patients with atrial fibrillation during NOAC treatment and (2) to evaluate the role of CHA 2 DS 2 -VASc and HAS-BLED scores in the same setting. Methods: Cases were consecutive patients with atrial fibrillation who had ICH during NOAC treatment. Controls were consecutive patients with atrial fibrillation who did not have ICH during NOAC treatment. As within the CHA 2 DS 2 -VASc and HAS-BLED scores there are some risk factors in common, several multivariable logistic regression models were performed to identify independent prespecified predictors for ICH events. Results: Four hundred nineteen cases (mean age, 78.8±8.1 years) and 1526 controls (mean age, 76.0±10.3 years) were included in the study. From the different models performed, independent predictors of ICH were increasing age, concomitant use of antiplatelet agents, active malignancy, high risk of fall, hyperlipidemia, low clearance of creatinine, peripheral artery disease, and white matter changes. Low doses of NOACs (given according to label or not) and congestive heart failure were inversely associated with the risk of ICH. HAS-BLED and CHA 2 DS 2 -VASc scores performed poorly in predicting ICH with areas under the curves of 0.496 (95% CI, 0.468–0.525) and 0.530 (95% CI, 0.500–0.560), respectively. Conclusions: Several risk factors were associated to ICH in patients treated with NOACs for stroke prevention but not HAS-BLED and CHA 2 DS 2 -VASc scores. more...
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- 2021
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18. Multi-frequency Saturation Transfer Difference NMR to Characterize Weak Protein–Ligand Complexes
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Serena Monaco and Jesús Angulo
- Abstract
Weak protein–ligand interactions have been demonstrated to play key roles in biological processes, particularly in those involving quick cellular responses after certain stimuli (e.g. signal transduction). Although powerful biophysical techniques are available to gain high-resolution structural information of protein–ligand complexes of high affinity, NMR spectroscopy has been demonstrated to stand out among them for protein–ligand studies within the limit of weak affinity. In particular, ligand-based NMR techniques allow the detection and quantification of weak biomolecular binding processes, where saturation transfer difference (STD) NMR techniques have demonstrated through the years their strong ability to not only detect binding processes but also to provide structural information about the ligand mode of binding in the receptor-binding pocket, a highly valuable piece of information for the further development of enhanced binders along the process of drug discovery. This is particularly useful in fragment-based drug-discovery approaches, where the binding of the identified initial small fragments tends to fall within the low affinity range of the spectrum. In this chapter we briefly introduce the different classical STD NMR approaches, and later focus in detail on novel developments based on multi-frequency STD NMR experiments, which expand further the analytical capabilities of STD NMR, exemplified by the DEEP-STD NMR protocol, by providing also some key information on the nature of the protein residues in contact with the ligands in the bond state. more...
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- 2022
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19. Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes
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Michele Venti, Walter Ageno, Alfonso Ciccone, Luana Gentile, Vanessa Gourbali, Antonio Baldi, Elisa Grifoni, László Csiba, Cataldo D'Amore, Prasanna Tadi, Yuriy Flomin, Rossana Tassi, Sung Il Sohn, Bruno Bonetti, Patrik Michel, Erika Schirinzi, Alessandro Padovani, Cindy Tiseo, Maria Luisa De Lodovici, Odysseas Kargiotis, Konstantinos Vadikolias, Shadi Yaghi, Maurizio Paciaroni, Georgios Tsivgoulis, Enrico Maria Lotti, Manuel Cappellari, Lilla Szabó, Ashraf Eskandari, Federica Letteri, Leonardo Ulivi, Chrissoula Liantinioti, Valeria Caso, Lina Palaiodimou, Dirk Deleu, Jesse Dawson, Licia Denti, Konstantinos Makaritsis, Gianni Lorenzini, Marina Mannino, Monica Acciarresi, Miriam Maccarrone, Nicola Mumoli, Marta Bellesini, Simona Sacco, George Athanasakis, Umberto Scoditti, Maurizio Acampa, Giuseppe Martini, Brian Mac Grory, Alberto Rigatelli, Kristian Barlinn, Vieri Vannucchi, Serena Monaco, Efstathia Karagkiozi, Elisa Giorli, Francesca Guideri, Martina Giuntini, Dorjan Zabzuni, Davide Imberti, Giorgio Silvestrelli, Luca Masotti, Loris Poli, Karen L. Furie, Alessio Pieroni, Marialuisa Zedde, Franco Galati, Andrea Alberti, Giancarlo Agnelli, Jessica Barlinn, Turgut Tatlisumak, Maria Chiara Caselli, Boris Doronin, Liisa Tomppo, Kennedy R. Lees, Mario Maimone Baronello, Maria Giulia Mosconi, Jukka Putaala, Tiziana Tassinari, Azmil H. Abdul-Rahim, Peter Vanacker, Christina Rueckert, Valentina Bogini, Alessandro Pezzini, Francesco Corea, Giovanni Orlandi, Simona Marcheselli, Michela Giustozzi, Theodore Karapanayiotides, Michelangelo Mancuso, George Ntaios, Fabio Bandini, Vera Volodina, Nicola Giannini, Cesare Porta, Danilo Toni, Alberto Chiti, and Massimo Del Sette more...
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Severe bleeding ,medicine.medical_specialty ,Stroke recurrence ,Infarction ,stroke recurrence ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Original Research Articles ,Internal medicine ,Ischaemic stroke ,Acute stroke ,Medicine ,atrial fibrillation ,In patient ,Acute ischemic stroke ,business.industry ,Atrial fibrillation ,medicine.disease ,Cardiology ,Human medicine ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery - Abstract
Introduction The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing. Materials and Methods Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39–2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16–1.80). Discussion our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events. Conclusions Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT. more...
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- 2020
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20. Recurrent Ischemic Stroke and Bleeding in Patients With Atrial Fibrillation Who Suffered an Acute Stroke While on Treatment With Nonvitamin K Antagonist Oral Anticoagulants: The RENO-EXTEND Study
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Maurizio Paciaroni, Valeria Caso, Giancarlo Agnelli, Maria Giulia Mosconi, Michela Giustozzi, David Julian Seiffge, Stefan T. Engelter, Philippe Lyrer, Alexandros A. Polymeris, Lilian Kriemler, Annaelle Zietz, Jukka Putaala, Daniel Strbian, Liisa Tomppo, Patrik Michel, Davide Strambo, Alexander Salerno, Suzette Remillard, Manuela Buehrer, Odessa Bavaud, Peter Vanacker, Susanna Zuurbier, Laetitia Yperzeele, Caroline M.J. Loos, Manuel Cappellari, Andrea Emiliani, Marialuisa Zedde, Azmil Abdul-Rahim, Jesse Dawson, Robert Cronshaw, Erika Schirinzi, Massimo Del Sette, Christoph Stretz, Narendra Kala, Michael Reznik, Ashley Schomer, Brian Mac Grory, Mahesh Jayaraman, Ryan McTaggart, Shadi Yaghi, Karen L. Furie, Luca Masotti, Elisa Grifoni, Danilo Toni, Angela Risitano, Anne Falcou, Luca Petraglia, Enrico Maria Lotti, Marina Padroni, Lucia Pavolucci, Piergiorgio Lochner, Giorgio Silvestrelli, Alfonso Ciccone, Andrea Alberti, Michele Venti, Laura Traballi, Chiara Urbini, Odysseas Kargiotis, Alessandro Rocco, Marina Diomedi, Simona Marcheselli, Pietro Caliandro, Aurelia Zauli, Giuseppe Reale, Kateryna Antonenko, Eugenia Rota, Tiziana Tassinari, Valentina Saia, Francesco Palmerini, Paolo Aridon, Valentina Arnao, Serena Monaco, Salvatore Cottone, Antonio Baldi, Cataldo D’Amore, Walter Ageno, Samuela Pegoraro, George Ntaios, Dimitrios Sagris, Sotirios Giannopoulos, Maria Kosmidou, Evangelos Ntais, Michele Romoli, Leonardo Pantoni, Silvia Rosa, Pierluigi Bertora, Alberto Chiti, Isabella Canavero, Carlo Emanuele Saggese, Maurizio Plocco, Elisa Giorli, Lina Palaiodimou, Eleni Bakola, Georgios Tsivgoulis, Fabio Bandini, Antonio Gasparro, Valeria Terruso, Marina Mannino, Alessandro Pezzini, Raffaele Ornello, Simona Sacco, Nemanja Popovic, Umberto Scoditti, Antonio Genovese, Licia Denti, Yuriy Flomin, Michelangelo Mancuso, Elena Ferrari, Maria Chiara Caselli, Leonardo Ulivi, Nicola Giannini, Gian Marco De Marchis, Paciaroni, Maurizio, Caso, Valeria, Agnelli, Giancarlo, Mosconi, Maria Giulia, Giustozzi, Michela, Seiffge, David Julian, Engelter, Stefan T, Lyrer, Philippe, Polymeris, Alexandros A, Kriemler, Lilian, Zietz, Annaelle, Putaala, Jukka, Strbian, Daniel, Tomppo, Liisa, Michel, Patrik, Strambo, Davide, Salerno, Alexander, Remillard, Suzette, Buehrer, Manuela, Bavaud, Odessa, Vanacker, Peter, Zuurbier, Susanna, Yperzeele, Laetitia, Loos, Caroline M J, Cappellari, Manuel, Emiliani, Andrea, Zedde, Marialuisa, Abdul-Rahim, Azmil, Dawson, Jesse, Cronshaw, Robert, Schirinzi, Erika, Del Sette, Massimo, Stretz, Christoph, Kala, Narendra, Reznik, Michael, Schomer, Ashley, Grory, Brian Mac, Jayaraman, Mahesh, McTaggart, Ryan, Yaghi, Shadi, Furie, Karen L, Masotti, Luca, Grifoni, Elisa, Toni, Danilo, Risitano, Angela, Falcou, Anne, Petraglia, Luca, Lotti, Enrico Maria, Padroni, Marina, Pavolucci, Lucia, Lochner, Piergiorgio, Silvestrelli, Giorgio, Ciccone, Alfonso, Alberti, Andrea, Venti, Michele, Traballi, Laura, Urbini, Chiara, Kargiotis, Odyssea, Rocco, Alessandro, Diomedi, Marina, Marcheselli, Simona, Caliandro, Pietro, Zauli, Aurelia, Reale, Giuseppe, Antonenko, Kateryna, Rota, Eugenia, Tassinari, Tiziana, Saia, Valentina, Palmerini, Francesco, Aridon, Paolo, Arnao, Valentina, Monaco, Serena, Cottone, Salvatore, Baldi, Antonio, D'Amore, Cataldo, Ageno, Walter, Pegoraro, Samuela, Ntaios, George, Sagris, Dimitrio, Giannopoulos, Sotirio, Kosmidou, Maria, Ntais, Evangelo, Romoli, Michele, Pantoni, Leonardo, Rosa, Silvia, Bertora, Pierluigi, Chiti, Alberto, Canavero, Isabella, Saggese, Carlo Emanuele, Plocco, Maurizio, Giorli, Elisa, Palaiodimou, Lina, Bakola, Eleni, Tsivgoulis, Georgio, Bandini, Fabio, Gasparro, Antonio, Terruso, Valeria, Mannino, Marina, Pezzini, Alessandro, Ornello, Raffaele, Sacco, Simona, Popovic, Nemanja, Scoditti, Umberto, Genovese, Antonio, Denti, Licia, Flomin, Yuriy, Mancuso, Michelangelo, Ferrari, Elena, Caselli, Maria Chiara, Ulivi, Leonardo, Giannini, Nicola, De Marchis, Gian Marco, and Neurology more...
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Oral ,Advanced and Specialized Nursing ,hypertension ,recurrence ,anticoagulant ,Administration, Oral ,Anticoagulants ,Hemorrhage ,Settore MED/26 ,Brain Ischemia ,Stroke ,Risk Factors ,Administration ,Atrial Fibrillation ,Humans ,Settore MED/26 - Neurologia ,Human medicine ,Neurology (clinical) ,Prospective Studies ,Cardiology and Cardiovascular Medicine ,atrial fibrillation ,ischemic stroke ,Ischemic Stroke - Abstract
Background: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. Methods: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. Results: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA 2 DS 2 -VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0–1.3] for each point increase; P =0.05) and hypertension (OR, 2.3 [95% CI, 1.0–5.1]; P =0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0–1.2] for each year increase; P =0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4–14.2]; P =0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4–5.5]; P =0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8–1.7]). Conclusions: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding. more...
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- 2022
21. Cross-reactivity of glycan-reactive HIV-1 broadly neutralizing antibodies with parasite glycans
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Isabella Huettner, Stefanie A. Krumm, Sonia Serna, Katarzyna Brzezicka, Serena Monaco, Samuel Walpole, Angela van Diepen, Fiona Allan, Thomas Hicks, Simon Kimuda, Aidan M. Emery, Elise Landais, Cornelis H. Hokke, Jesus Angulo, Niels Reichardt, Katie J. Doores, Susan Allen, William Kilembe, Shabir Lakhi, Mubiana Inambao, Etienne Karita, Anatoli Kamali, Eduard J. Sanders, Omu Anzala, Vinodh Edward, Linda-Gail Bekker, Jianming Tang, Jill Gilmour, Eric Hunter, Matt Price, Medical Research Council (UK), Rosetrees Trust, Fondation Dormeur, Vaduz, National Institute for Health Research (UK), NIHR Biomedical Research Centre (UK), NHS Foundation Trust, Kings College London, Ministerio de Educación y Ciencia (España), Agencia Estatal de Investigación (España), Wellcome Trust, Ministerio de Ciencia, Innovación y Universidades (España), Biotechnology and Biological Sciences Research Council (UK), Bill & Melinda Gates Foundation, Ministry of Foreign Affairs (Denmark), Irish Aid, World Bank Group, Ministry of Foreign Affairs (The Netherlands), Norwegian Agency for Development Cooperation, European Commission, Department for International Development (UK), and United States Agency for International Development more...
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carbohydrates (lipids) ,Polysaccharides ,parasitic diseases ,HIV-1 ,Animals ,Humans ,virus diseases ,HIV Infections ,Parasites ,HIV Antibodies ,Antibodies, Neutralizing ,Broadly Neutralizing Antibodies ,General Biochemistry, Genetics and Molecular Biology - Abstract
The HIV-1 Envelope glycoprotein (Env) is the sole target for broadly neutralizing antibodies (bnAbs). Env is heavily glycosylated with host-derived N-glycans, and many bnAbs bind to, or are dependent upon, Env glycans for neutralization. Although glycan-binding bnAbs are frequently detected in HIV-infected individuals, attempts to elicit them have been unsuccessful because of the poor immunogenicity of Env N-glycans. Here, we report cross-reactivity of glycan-binding bnAbs with self- and non-self N-glycans and glycoprotein antigens from different life-stages of Schistosoma mansoni. Using the IAVI Protocol C HIV infection cohort, we examine the relationship between S. mansoni seropositivity and development of bnAbs targeting glycan-dependent epitopes. We show that the unmutated common ancestor of the N332/V3-specific bnAb lineage PCDN76, isolated from an HIV-infected donor with S. mansoni seropositivity, binds to S. mansoni cercariae while lacking reactivity to gp120. Overall, these results present a strategy for elicitation of glycan-reactive bnAbs which could be exploited in HIV-1 vaccine development., This project has received funding from the European Union’s Horizon 2020 Research and Innovation program under grant agreement 681137 (to K.J.D. and I.H.), the Medical Research Council (MRC) (to K.J.D. [MR/K024426/1]), The Rosetrees Trust (to K.J.D. [M686]) and Fondation Dormeur, Vaduz (to K.J.D). This research was funded or supported by the National Institute for Health Research Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London and/or the NIHR Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the National Health Service (NHS), the National Institute for Health Research (NIHR), or the Department of Health. N.R. acknowledges funding from Ministry of Science and Education grants CTQ2017-90039-R, RTC-2017-6126-1, and CTQ2011-27874 (fellowship to K.B.) and the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency (grant MDM-2017-0720). F.A. was funded by the Wellcome Trust (104958/Z/14/Z). J.A. was supported by the Spanish Ministry of Science, Innovation and Universities through the grant PID2019-109395GB-I00. J.A. and S.M. acknowledge support of BBSRC (grant BB/P010660/1). T.H. and S.W. were funded by Biotechnology and Biological Sciences Research Council (BBSRC) Norwich Research Park Doctoral Training Grant BB/M011216/1. IAVI’s work is made possible by generous support from many donors, including the Bill & Melinda Gates Foundation, the Ministry of Foreign Affairs of Denmark, Irish Aid, the Ministry of Finance of Japan in partnership with The World Bank, the Ministry of Foreign Affairs of the Netherlands, the Norwegian Agency for Development Cooperation, the United Kingdom Department for International Development (DFID), and the United States Agency for International Development. The full list of IAVI donors is available at www.iavi.org. Brendan McAtarsney and Jonathan Hare from the IAVI Human Immunology Lab (HIL) for coordinating the samples transfers and shipments. Monica Agromayor and the KCL Nikon Centre for assistance and advice on confocal microscopy. NMRI strain Schistosoma mansoni-infected Biomphalaria glabrata snails were provided by the NIAID Schistosomiasis Resource Center, Rockville, USA. more...
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- 2022
22. Causes and Risk Factors of Cerebral Ischemic Events in Patients With Atrial Fibrillation Treated With Non–Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention
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Panagiotis Papamichalis, Marina Padroni, Katiuscia Nardi, Maria Cristina Vedovati, Erika Schirinzi, Konstantinos Makaritsis, Serena Monaco, Valentina Saia, Karen L. Furie, Giancarlo Agnelli, Kennedy R. Lees, Dirk Deleu, Sotirios Giannopoulos, Azmil H. Abdul-Rahim, Miriam Maccarrone, Tiziana Tassinari, Jukka Putaala, Alexandros A Polymeris, Marina Diomedi, Elena Ferrari, Shadi Yaghi, Alexandra Rimoldi, Monica Acciarresi, Apostolos Komnos, Efstathia Karagkiozi, Elisabetta Toso, Gian Marco De Marchis, Maria Giulia Mosconi, Francesca Guideri, Aristeidis H. Katsanos, Luca Masotti, Piergiorgio Lochner, Angela Risitano, Danilo Toni, Elisa Giorli, Silvia Rosa, Alessandro Pezzini, Francesco Corea, Leonardo Pantoni, Boris Doronin, Filippo Angelini, Giovanni Orlandi, Simona Marcheselli, Chrysoula Liantinioti, Michela Giustozzi, Licia Denti, Manuel Cappellari, Marialuisa Zedde, Cataldo D'Amore, Patrizia Pierini, Elena Pinuccia Verrengia, Kateryna Antonenko, Stefan T. Engelter, Giorgio Silvestrelli, Patrik Michel, Bruno Bonetti, Leonardo Ulivi, Alessandro Rocco, Nicola Mumoli, Lina Palaiodimou, Andrea Alberti, Marina Mannino, Maurizio Paciaroni, Nemanja Popovic, Sung Il Sohn, Marija Zarkov, Odysseas Kargiotis, Ashraf Eskandari, Antonio Baldi, Massimo Del Sette, Michelangelo Mancuso, Michele Venti, Walter Ageno, Alfonso Ciccone, Alberto Chiti, Kalliopi Perlepe, George Ntaios, Silvia Galliazzo, Fabio Bandini, Vera Volodina, Pierluigi Bertora, Nicola Giannini, Georgios Tsivgoulis, Maurizio Acampa, David J. Seiffge, Elisa Grifoni, Brian Mac Grory, Paola Santalucia, Yuriy Flomin, Rossana Tassi, Valeria Caso, Enrico Maria Lotti, and Giuseppe Martini more...
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Oral ,Male ,medicine.medical_specialty ,medicine.drug_class ,Administration, Oral ,030204 cardiovascular system & hematology ,Risk Assessment ,Brain Ischemia ,Settore MED/11 ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Atrial Fibrillation ,atrial fibrillation ,humans ,prevention and control ,risk factors ,stroke ,80 and over ,medicine ,Humans ,In patient ,Stroke ,Aged ,Aged, 80 and over ,Advanced and Specialized Nursing ,business.industry ,Age Factors ,Warfarin ,Anticoagulants ,Atrial fibrillation ,Middle Aged ,Vitamin K antagonist ,medicine.disease ,3. Good health ,Stroke prevention ,Administration ,Cardiology ,Settore MED/26 - Neurologia ,Female ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background and Purpose— Despite treatment with oral anticoagulants, patients with nonvalvular atrial fibrillation (AF) may experience ischemic cerebrovascular events. The aims of this case-control study in patients with AF were to identify the pathogenesis of and the risk factors for cerebrovascular ischemic events occurring during non–vitamin K antagonist oral anticoagulants (NOACs) therapy for stroke prevention. Methods— Cases were consecutive patients with AF who had acute cerebrovascular ischemic events during NOAC treatment. Controls were consecutive patients with AF who did not have cerebrovascular events during NOACs treatment. Results— Overall, 713 cases (641 ischemic strokes and 72 transient ischemic attacks; median age, 80.0 years; interquartile range, 12; median National Institutes of Health Stroke Scale on admission, 6.0; interquartile range, 10) and 700 controls (median age, 72.0 years; interquartile range, 8) were included in the study. Recurrent stroke was classified as cardioembolic in 455 cases (63.9%) according to the A-S-C-O-D (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; D, dissection) classification. On multivariable analysis, off-label low dose of NOACs (odds ratio [OR], 3.18; 95% CI, 1.95–5.85), atrial enlargement (OR, 6.64; 95% CI, 4.63–9.52), hyperlipidemia (OR, 2.40; 95% CI, 1.83–3.16), and CHA 2 DS 2 -VASc score (OR, 1.72 for each point increase; 95% CI, 1.58–1.88) were associated with ischemic events. Among the CHA 2 DS 2 -VASc components, age was older and presence of diabetes mellitus, congestive heart failure, and history of stroke or transient ischemic attack more common in patients who had acute cerebrovascular ischemic events. Paroxysmal AF was inversely associated with ischemic events (OR, 0.45; 95% CI, 0.33–0.61). Conclusions— In patients with AF treated with NOACs who had a cerebrovascular event, mostly but not exclusively of cardioembolic pathogenesis, off-label low dose, atrial enlargement, hyperlipidemia, and high CHA 2 DS 2 -VASc score were associated with increased risk of cerebrovascular events. more...
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- 2019
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23. Anticoagulation After Stroke in Patients With Atrial Fibrillation
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Francesca Guideri, Martina Giuntini, Luca Masotti, Sung Il Sohn, László Csiba, Marta Bellesini, Ludovica Anna Cimini, Lars-Peder Pallesen, Michele Venti, Walter Ageno, Efstathia Karagkiozi, Davide Imberti, Leonardo Ulivi, Alessandro Padovani, Giancarlo Agnelli, Giovanni Orlandi, Danilo Toni, Gianni Lorenzini, Alfonso Ciccone, Dirk Deleu, Licia Denti, Federica Letteri, Giorgio Bono, Karen L. Furie, Vieri Vannucchi, Miriam Maccarrone, Cecilia Becattini, Theodore Karapanayiotides, Domenico Consoli, Monica Carletti, Jukka Putaala, Cataldo D'Amore, Nicola Mumoli, Maria Chondrogianni, Alberto Chiti, Peter Vanacker, Marialuisa Zedde, Michelangelo Mancuso, Boris Doronin, Giorgio Silvestrelli, Vanessa Gourbali, Simona Sacco, Manuel Cappellari, Giuseppe Martini, Christina Rueckert, Faisal Ibrahim, George Ntaios, Serena Monaco, Franco Galati, Antonio Carolei, Alessio Pieroni, Dorjan Zabzuni, Simona Marcheselli, Naveed Akhtar, Prasanna Tadi, Loris Poli, Mario Maimone Baronello, Antonio Baldi, Fabio Bandini, Vera Volodina, George Athanasakis, Yuriy Flomin, Chrysoula Liantinioti, Nicola Giannini, Umberto Scoditti, Elisa Giorli, Gayane Melikyan, Alessandro Pezzini, Alessia Lanari, Andrea Alberti, Konstantinos Makaritsis, Cindy Tiseo, Francesco Corea, Rossana Tassi, Georgios Tsivgoulis, Maria Luisa De Lodovici, Enrico Maria Lotti, Odysseas Kargiotis, Jessica Barlinn, Massimo Del Sette, Konstantinos Vadikolias, Paolo Bovi, Kennedy R. Lees, Riccardo Altavilla, Turgut Tatlisumak, Liisa Tomppo, Maurizio Paciaroni, Lilla Szabó, Alberto Rigatelli, Kristian Barlinn, Monica Acciarresi, Patrik Michel, Tiziana Tassinari, Maurizio Acampa, Maria Giulia Mosconi, Shadi Yaghi, Jessica Fusaro, Valeria Caso, Sebastiano D'Anna, Azmil H. Abdul-Rahim, Gino Gialdini, HUS Neurocenter, Department of Neurosciences, and Neurologian yksikkö more...
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anticoagulants ,medicine.medical_specialty ,LEUKOARAIOSIS ,ARTERIAL TERRITORIES ,030204 cardiovascular system & hematology ,3124 Neurology and psychiatry ,03 medical and health sciences ,0302 clinical medicine ,atrial fibrillation ,humans ,incidence ,secondary prevention ,Internal medicine ,medicine ,In patient ,ACUTE ISCHEMIC-STROKE ,Stroke ,METAANALYSIS ,Cerebral Hemorrhage ,RISK ,Advanced and Specialized Nursing ,Secondary prevention ,OUTCOMES ,Cardioembolic stroke ,Heparin ,business.industry ,Incidence (epidemiology) ,Low-Molecular-Weight ,3112 Neurosciences ,Atrial fibrillation ,HUMAN BRAIN ,medicine.disease ,Anticoagulants ,Atrial Fibrillation ,Heparin, Low-Molecular-Weight ,Humans ,Secondary Prevention ,3. Good health ,Heparin.low molecular weight ,3121 General medicine, internal medicine and other clinical medicine ,Cardiology ,Human medicine ,HEMORRHAGIC TRANSFORMATION ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background and Purpose— Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods— We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results— Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients ( P =0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4–3.7; P P =0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2–4.9; P =0.01) end points separately. Conclusions— Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients. more...
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- 2019
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24. The clinical spectrum of reversible cerebral vasoconstriction syndrome: The Italian Project on Stroke at Young Age (IPSYS)
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Alessandro Padovani, Valeria De Giuli, Andrea Morotti, Alessandro Pezzini, Carlo Piantadosi, Carlo Gandolfo, Filomena Caria, Cristiano Azzini, Antonella Toriello, Piergiorgio Lochner, Alessandro Adami, Paolo Cerrato, Carlo Dallocchio, Maurizio Paciaroni, Cristina Motto, Serena Monaco, Valeria Bignamini, Loris Poli, Enrico Maria Lotti, Carla Zanferrari, Marialuisa Zedde, Alberto Chiti, Paolo Costa, Simona Marcheselli, Luca Quartuccio, Massimo Del Sette, Sabrina Anticoli, Maria Luisa DeLodovici, Anna Bersano, Maurizia Rasura, Sandro Sanguigni, Massimo Gamba, Maurizio Melis, Giorgio Silvestrelli, Fabio Melis, Mauro Gentile, Andrea Zini, and Corrado Lodigiani more...
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intracranial ,medicine.medical_specialty ,Headache Disorders, Primary ,male ,Neuroimaging ,Internal medicine ,primary ,italy ,middle aged ,medicine ,Vasospasm, Intracranial ,humans ,Stroke ,vasospasm ,Thunderclap headaches ,reversible cerebral vasoconstriction syndrome (rcvs) ,business.industry ,adult ,stroke ,thunderclap headache ,female ,headache disorders, primary ,retrospective studies ,syndrome ,General Medicine ,medicine.disease ,Reversible cerebral vasoconstriction syndrome ,Large cohort ,Young age ,headache disorders ,Cardiology ,Neurology (clinical) ,medicine.symptom ,business ,Vasoconstriction - Abstract
Introduction To describe clinical, neuroimaging, and laboratory features of a large cohort of Italian patients with reversible cerebral vasoconstriction syndrome. Methods In the setting of the multicenter Italian Project on Stroke at Young Age (IPSYS), we retrospectively enrolled patients with a diagnosis of definite reversible cerebral vasoconstriction syndrome according to the International Classification of Headache Disorders (ICHD)-3 beta criteria (6.7.3 Headache attributed to reversible cerebral vasoconstriction syndrome, imaging-proven). Clinical manifestations, neuroimaging, treatment, and clinical outcomes were evaluated in all patients. Characteristics of reversible cerebral vasoconstriction syndrome without typical causes (“idiopathic reversible cerebral vasoconstriction syndrome”) were compared with those of reversible cerebral vasoconstriction syndrome related to putative causative factors (“secondary reversible cerebral vasoconstriction syndrome”). Results A total of 102 patients (mean age, 47.2 ± 13.9 years; females, 85 [83.3%]) qualified for the analysis. Thunderclap headache at presentation was reported in 69 (67.6%) patients, and it typically recurred in 42 (60.9%). Compared to reversible cerebral vasoconstriction syndrome cases related to putative etiologic conditions (n = 21 [20.6%]), patients with idiopathic reversible cerebral vasoconstriction syndrome (n = 81 [79.4%]) were significantly older (49.2 ± 13.9 vs. 39.5 ± 11.4 years), had more frequently typical thunderclap headache (77.8% vs. 28.6%) and less frequently neurological complications (epileptic seizures, 11.1% vs. 38.1%; cerebral infarction, 6.1% vs. 33.3%), as well as concomitant reversible brain edema (25.9% vs. 47.6%). Conclusions Clinical manifestations and putative etiologies of reversible cerebral vasoconstriction syndrome in our series are slightly different from those observed in previous cohorts. This variability might be partly related to the coexistence of precipitating conditions with a putative etiologic role on disease occurrence. more...
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- 2019
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25. Fucosyltransferase-specific inhibition via next generation of fucose mimetics
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Thomas Hicks, Ana García-García, Francisco Corzana, Ramon Hurtado-Guerrero, Serena Monaco, Laura Ceballos-Laita, Kyle C. Martin, Barbara Richichi, Jesús Angulo, Jacopo Tricomi, and Robert Sackstein
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Glycan ,Fucosyltransferase ,Cell ,01 natural sciences ,Catalysis ,Fucose ,Gene Expression Regulation, Enzymologic ,Fucosyltransferases ,03 medical and health sciences ,chemistry.chemical_compound ,Glycomimetic ,Cell Line, Tumor ,Materials Chemistry ,medicine ,Humans ,Binding site ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,biology ,010405 organic chemistry ,Metals and Alloys ,Mesenchymal Stem Cells ,General Chemistry ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,0104 chemical sciences ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,medicine.anatomical_structure ,Enzyme ,Biochemistry ,chemistry ,Ceramics and Composites ,biology.protein - Abstract
The ability to custom-modify cell surface glycans holds great promise for treatment of a variety of diseases. We propose a glycomimetic ofl-fucose that markedly inhibits the creation of sLeXby FTVI and FTVII, but has no effect on creation of LeXby FTIX. Our findings thus indicate that selective suppression of sLex display can be achieved, and STD-NMR studies surprisingly reveal that the mimetic does not compete with GDP-fucose at the enzymatic binding site. more...
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- 2021
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26. Fucosidases from the human gut symbiont Ruminococcus gnavus
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Samuel Walpole, Osmond D. Rebello, Haiyang Wu, Martin A. Walsh, Serena Monaco, Paulina A. Urbanowicz, Emmanuelle H. Crost, Didier Ndeh, Anna Colvile, Jesús Angulo, Daniel I. R. Spencer, C. David Owen, Nathalie Juge, Thomas Hicks, Chloe Bennati-Granier, and Universidad de Sevilla. Departamento de Química orgánica more...
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Glycan ,Glycoconjugate ,Oligosaccharides ,Gut microbiota ,Gut flora ,Substrate Specificity ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Bacterial Proteins ,Ruminococcus gnavus ,Polysaccharides ,Humans ,Glycoside hydrolase ,Fucosidase ,Molecular Biology ,030304 developmental biology ,Pharmacology ,chemistry.chemical_classification ,alpha-L-Fucosidase ,0303 health sciences ,Clostridiales ,biology ,Chemistry ,030302 biochemistry & molecular biology ,Cell Biology ,biology.organism_classification ,Antennary fucose ,Sialic acid ,Gastrointestinal Microbiome ,Gastrointestinal Tract ,Mucus ,Mucin glycosylation ,Sialyl-Lewis X ,Biochemistry ,biology.protein ,Molecular Medicine ,Original Article ,Lewis epitopes ,Glycoconjugates - Abstract
The availability and repartition of fucosylated glycans within the gastrointestinal tract contributes to the adaptation of gut bacteria species to ecological niches. To access this source of nutrients, gut bacteria encode α-l-fucosidases (fucosidases) which catalyze the hydrolysis of terminal α-l-fucosidic linkages. We determined the substrate and linkage specificities of fucosidases from the human gut symbiont Ruminococcus gnavus. Sequence similarity network identified strain-specific fucosidases in R. gnavus ATCC 29149 and E1 strains that were further validated enzymatically against a range of defined oligosaccharides and glycoconjugates. Using a combination of glycan microarrays, mass spectrometry, isothermal titration calorimetry, crystallographic and saturation transfer difference NMR approaches, we identified a fucosidase with the capacity to recognize sialic acid-terminated fucosylated glycans (sialyl Lewis X/A epitopes) and hydrolyze α1–3/4 fucosyl linkages in these substrates without the need to remove sialic acid. Molecular dynamics simulation and docking showed that 3′-Sialyl Lewis X (sLeX) could be accommodated within the binding site of the enzyme. This specificity may contribute to the adaptation of R. gnavus strains to the infant and adult gut and has potential applications in diagnostic glycomic assays for diabetes and certain cancers. more...
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- 2021
27. Clinical Features of Patients with Cervical Artery Dissection and Fibromuscular Dysplasia
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Sonia Bonacina, Mario Grassi, Marialuisa Zedde, Andrea Zini, Anna Bersano, Carlo Gandolfo, Giorgio Silvestrelli, Claudio Baracchini, Paolo Cerrato, Corrado Lodigiani, Simona Marcheselli, Maurizio Paciaroni, Maurizia Rasura, Manuel Cappellari, Massimo Del Sette, Anna Cavallini, Andrea Morotti, Giuseppe Micieli, Enrico Maria Lotti, Maria Luisa DeLodovici, Mauro Gentile, Mauro Magoni, Cristiano Azzini, Maria Vittoria Calloni, Elisa Giorli, Massimiliano Braga, Paolo La Spina, Fabio Melis, Rossana Tassi, Valeria Terruso, Rocco Salvatore Calabrò, Valeria Piras, Alessia Giossi, Martina Locatelli, Valentina Mazzoleni, Debora Pezzini, Sandro Sanguigni, Carla Zanferrari, Marina Mannino, Irene Colombo, Carlo Dallocchio, Patrizia Nencini, Valeria Bignamini, Alessandro Adami, Eugenio Magni, Rita Bella, Alessandro Padovani, Alessandro Pezzini, Rosario Pascarella, Maria Sessa, Emma Scelzo, Monica Laura Bandettini di Poggio, Francesca Boscain, Andrea Naldi, Valeria Caso, Massimo Gamba, Ilaria Casetta, Stefano Forlivesi, Giampaolo Tomelleri, Elena Schirinzi, Elena Verrengia, Graziamaria Nuzzaco, Sandro Beretta, Rossella Musolino, Daniele Imperiale, Maurizio Acampa, Antonio Gasparro, Maurizio Melis, Francesco Fisicaro, Ignazio Santilli, Manuel Corato, Marina Padroni, Eleonora Leuci, Federico Mazzacane, Alessandra Gaiani, Federica Assenza, Lucia Princiotta Cariddi, Cristina Sarti, Serena Monaco, Emanuele Puca, and Ludovico Ciolli more...
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Adult ,Male ,medicine.medical_specialty ,demography ,Adolescent ,Cervical Artery ,Migraine Disorders ,Dissection (medical) ,Fibromuscular dysplasia ,030204 cardiovascular system & hematology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,cohort studies ,Recurrence ,Prevalence ,medicine ,Fibromuscular Dysplasia ,Humans ,risk factors ,dissection ,follow-up studies ,Carotid Arteries ,Female ,Italy ,Middle Aged ,Proportional Hazards Models ,Risk Factors ,Stroke ,Vertebral Artery Dissection ,Advanced and Specialized Nursing ,business.industry ,Settore MED/09 - MEDICINA INTERNA ,Follow up studies ,medicine.disease ,Neurology (clinical) ,Radiology ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery ,Cohort study - Abstract
Background and Purpose: Observational studies have suggested a link between fibromuscular dysplasia and spontaneous cervical artery dissection (sCeAD). However, whether patients with coexistence of the two conditions have distinctive clinical characteristics has not been extensively investigated. Methods: In a cohort of consecutive patients with first-ever sCeAD, enrolled in the setting of the multicenter IPSYS CeAD study (Italian Project on Stroke in Young Adults Cervical Artery Dissection) between January 2000 and June 2019, we compared demographic and clinical characteristics, risk factor profile, vascular pathology, and midterm outcome of patients with coexistent cerebrovascular fibromuscular dysplasia (cFMD; cFMD+) with those of patients without cFMD (cFMD–). Results: A total of 1283 sCeAD patients (mean age, 47.8±11.4 years; women, 545 [42.5%]) qualified for the analysis, of whom 103 (8.0%) were diagnosed with cFMD+. In multivariable analysis, history of migraine (odds ratio, 1.78 [95% CI, 1.13–2.79]), the presence of intracranial aneurysms (odds ratio, 8.71 [95% CI, 4.06–18.68]), and the occurrence of minor traumas before the event (odds ratio, 0.48 [95% CI, 0.26–0.89]) were associated with cFMD. After a median follow-up of 34.0 months (25th to 75th percentile, 60.0), 39 (3.3%) patients had recurrent sCeAD events. cFMD+ and history of migraine predicted independently the risk of recurrent sCeAD (hazard ratio, 3.40 [95% CI, 1.58–7.31] and 2.07 [95% CI, 1.06–4.03], respectively) in multivariable Cox proportional hazards analysis. Conclusions: Risk factor profile of sCeAD patients with cFMD differs from that of patients without cFMD. cFMD and migraine are independent predictors of midterm risk of sCeAD recurrence. more...
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- 2021
28. Uncovering a novel molecular mechanism for scavenging sialic acids in bacteria
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Serena Monaco, Gavin H. Thomas, Emmanuele Severi, Micah O. Lee, Dimitrios Latousakis, Nathalie Juge, Andrew Bell, Jesús Angulo, James H. Naismith, and Universidad de Sevilla. Departamento de Química orgánica more...
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0301 basic medicine ,sialic acid transporters ,nuclear magnetic resonance (NMR) ,gut symbiosis ,Escherichia coli (E. coli) ,medicine.disease_cause ,2,7-anhydro-Neu5AC ,Biochemistry ,Cofactor ,03 medical and health sciences ,chemistry.chemical_compound ,Bacterial Proteins ,Oxidoreductase ,Ruminococcus gnavus ,medicine ,Escherichia coli ,Humans ,Molecular Biology ,oxidoreductase ,chemistry.chemical_classification ,Clostridiales ,mucin glycosylation ,030102 biochemistry & molecular biology ,biology ,gut microbiota ,Catabolism ,Genetic Complementation Test ,microbiology ,Mucins ,Cell Biology ,Sialic acid transport ,2,7-anhydro-Neu5Ac ,N-Acetylneuraminic Acid ,symbiosis ,Sialic acid ,STD NMR ,030104 developmental biology ,chemistry ,sialic acid ,biology.protein ,Enzymology ,NAD+ kinase ,Oxidoreductases ,oxidation-reduction (redox) - Abstract
The human gut symbiont Ruminococcus gnavus scavenges host-derived N-acetylneuraminic acid (Neu5Ac) from mucins by converting it to 2,7-anhydro-Neu5Ac. We previously showed that 2,7-anhydro-Neu5Ac is transported into R. gnavus ATCC 29149 before being converted back to Neu5Ac for further metabolic processing. However, the molecular mechanism leading to the conversion of 2,7-anhydro-Neu5Ac to Neu5Ac remained elusive. Using 1D and 2D NMR, we elucidated the multistep enzymatic mechanism of the oxidoreductase (RgNanOx) that leads to the reversible conversion of 2,7-anhydro-Neu5Ac to Neu5Ac through formation of a 4-keto-2-deoxy-2,3-dehydro-N-acetylneuraminic acid intermediate and NAD+ regeneration. The crystal structure of RgNanOx in complex with the NAD+ cofactor showed a protein dimer with a Rossman fold. Guided by the RgNanOx structure, we identified catalytic residues by site-directed mutagenesis. Bioinformatics analyses revealed the presence of RgNanOx homologues across Gram-negative and Gram-positive bacterial species and co-occurrence with sialic acid transporters. We showed by electrospray ionization spray MS that the Escherichia coli homologue YjhC displayed activity against 2,7-anhydro-Neu5Ac and that E. coli could catabolize 2,7-anhydro-Neu5Ac. Differential scanning fluorimetry analyses confirmed the binding of YjhC to the substrates 2,7-anhydro-Neu5Ac and Neu5Ac, as well as to co-factors NAD and NADH. Finally, using E. coli mutants and complementation growth assays, we demonstrated that 2,7-anhydro-Neu5Ac catabolism in E. coli depended on YjhC and on the predicted sialic acid transporter YjhB. These results revealed the molecular mechanisms of 2,7-anhydro-Neu5Ac catabolism across bacterial species and a novel sialic acid transport and catabolism pathway in E. coli. more...
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- 2020
29. A systematic review of neurological manifestations of SARS‐CoV‐2 infection: the devil is hidden in the details
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Ilijas Jelcic, Serena Monaco, Raphaël Bernard-Valnet, T. Akhvlediani, D. García Azorín, Michele Romoli, Johann Sellner, Pille Taba, Luca Mancinelli, University of Zurich, and Sellner, J
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Pediatrics ,medicine.medical_specialty ,Neurology ,encephalitis ,MEDLINE ,Clinical Neurology ,610 Medicine & health ,Disease ,SARS‐CoV‐2 ,neuroinvasion ,cerebrospinal fluid ,neurological complications ,03 medical and health sciences ,0302 clinical medicine ,COVID‐19 ,Epidemiology ,medicine ,Humans ,030212 general & internal medicine ,medicine.diagnostic_test ,business.industry ,SARS-CoV-2 ,COVID-19 ,Magnetic resonance imaging ,Original Articles ,medicine.disease ,Magnetic Resonance Imaging ,10040 Clinic for Neurology ,ddc ,2728 Neurology (clinical) ,Infectious disease (medical specialty) ,2808 Neurology ,Original Article ,Neurology (clinical) ,Nervous System Diseases ,business ,Meningitis ,030217 neurology & neurosurgery ,Encephalitis - Abstract
BACKGROUND AND PURPOSE We systematically reviewed available evidence for reports of neurological signs and symptoms in patients with COVID-19 to identify cases with severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection or immune-mediated reaction in the nervous system. METHODS We followed PRISMA guidelines and used the MEDLINE, EMBASE, Google Scholar, MedRxiv and ChinaXiv databases to search for articles on COVID-19 and nervous system involvement that were published from 1 January to 24 April 2020. Data on design, sample size, neurological assessment and related work-up were extracted. Biases were assessed with the Newcastle-Ottawa scale. RESULTS We analysed 27 publications on potential neuroinvasive or parainfectious neurological complications of COVID-19. The reports focused on smell and taste (n = 5) and evaluation of neurological symptoms and signs in cohorts (n = 5). There were cases of Guillain-Barre syndrome/Miller-Fisher syndrome/cranial neuropathy (seven cases), meningitis/encephalitis (nine cases) and various other conditions (five cases). The number of patients with examination of cerebrospinal fluid and, in particular, SARS-CoV-2 polymerase chain reaction was negligible. Two had a positive SARS-CoV-2 polymerase chain reaction examination of cerebrospinal fluid specimen. Study of potential parenchymal involvement with magnetic resonance imaging was rare. Only four reports received a rating of the highest quality standards. CONCLUSIONS This systematic review failed to establish comprehensive insights into nervous system manifestations of COVID-19 beyond immune-mediated complications in the aftermath of respiratory symptoms. The authors therefore provide guidance for more careful clinical, diagnostic and epidemiological studies to characterize the manifestations and burden of neurological disease caused by SARS-CoV-2 on behalf of the Infectious Disease Panel of the European Academy of Neurology. more...
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- 2020
30. Discovery of Small Molecule WWP2 Ubiquitin Ligase Inhibitors
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Serena Monaco, Jessica E. Watt, G. Richard Stephenson, Gregory R. Hughes, Samuel Walpole, Andrew M. Hemmings, Philip C. Bulman Page, Andrew Chantry, and Jesús Angulo
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0301 basic medicine ,Ubiquitin-Protein Ligases ,WWP2 ,Ligands ,Catalysis ,Small Molecule Libraries ,Inhibitory Concentration 50 ,03 medical and health sciences ,Ubiquitin ,Drug Discovery ,Humans ,Enzyme Inhibitors ,Nuclear Magnetic Resonance, Biomolecular ,Binding Sites ,biology ,Drug discovery ,Chemistry ,Organic Chemistry ,PTEN Phosphohydrolase ,General Chemistry ,Nuclear magnetic resonance spectroscopy ,Small molecule ,Protein Structure, Tertiary ,Ubiquitin ligase ,Molecular Docking Simulation ,030104 developmental biology ,Solubility ,Biochemistry ,Docking (molecular) ,biology.protein - Abstract
We have screened small molecule libraries specifically for inhibitors that target WWP2, an E3 ubiquitin ligase associated with tumour outgrowth and spread. Selected hits demonstrated dose‐dependent WWP2 inhibition, low micromolar IC50 values, and inhibition of PTEN substrate‐specific ubiquitination. Binding to WWP2 was confirmed by ligand‐based NMR spectroscopy. Furthermore, we used a combination of STD NMR, the recently developed DEEP‐STD NMR approach, and docking calculations, to propose for the first time an NMR‐validated 3D molecular model of a WWP2‐inhibitor complex. These first generation WWP2 inhibitors provide a molecular framework for informing organic synthetic approaches to improve activity and selectivity. more...
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- 2018
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31. Exploring Multi-Subsite Binding Pockets in Proteins: DEEP-STD NMR Fingerprinting and Molecular Dynamics Unveil a Cryptic Subsite at the GM1 Binding Pocket of Cholera Toxin B**
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Samuel Walpole, Ana T. Carmona, Serena Monaco, Hassan Doukani, Jesús Angulo, Ridvan Nepravishta, Macarena Martínez-Bailén, Maria Bergström, Javier Ramos-Soriano, Inmaculada Robina, Ministerio de Economía y Competitividad (España), Universidad de Sevilla. Departamento de Química orgánica, Universidad de Sevilla. FQM345: Química de Biomoléculas y Análogos, Ministerio de Economía y Competitividad (MINECO). España, Junta de Andalucía, and Universidad de Sevilla more...
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Cholera Toxin ,Magnetic Resonance Spectroscopy ,Stereochemistry ,Binding pocket ,G(M1) Ganglioside ,Molecular Dynamics Simulation ,Ligands ,010402 general chemistry ,medicine.disease_cause ,DEEP-STD NMR ,ligand-based NMR spectroscopy ,01 natural sciences ,Catalysis ,Molecular dynamics ,medicine ,cholera toxin inhibitors ,Binding Sites ,Full Paper ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Cholera toxin ,General Chemistry ,Nuclear magnetic resonance spectroscopy ,Full Papers ,Ligand (biochemistry) ,0104 chemical sciences ,Protein Binding Sites | Hot Paper ,Saturation transfer ,protein–ligand interactions ,multi-subsite binding pockets ,Protein Binding - Abstract
Ligand‐based NMR techniques to study protein–ligand interactions are potent tools in drug design. Saturation transfer difference (STD) NMR spectroscopy stands out as one of the most versatile techniques, allowing screening of fragments libraries and providing structural information on binding modes. Recently, it has been shown that a multi‐frequency STD NMR approach, differential epitope mapping (DEEP)‐STD NMR, can provide additional information on the orientation of small ligands within the binding pocket. Here, the approach is extended to a so‐called DEEP‐STD NMR fingerprinting technique to explore the binding subsites of cholera toxin subunit B (CTB). To that aim, the synthesis of a set of new ligands is presented, which have been subject to a thorough study of their interactions with CTB by weak affinity chromatography (WAC) and NMR spectroscopy. Remarkably, the combination of DEEP‐STD NMR fingerprinting and Hamiltonian replica exchange molecular dynamics has proved to be an excellent approach to explore the geometry, flexibility, and ligand occupancy of multi‐subsite binding pockets. In the particular case of CTB, it allowed the existence of a hitherto unknown binding subsite adjacent to the GM1 binding pocket to be revealed, paving the way to the design of novel leads for inhibition of this relevant toxin., Fingerprinting: A powerful protocol by using NMR spectroscopy and molecular dynamics to study multi‐subsite binding pockets has been developed. For cholera toxin subunit B (CTB), the combination of differential epitope mapping saturation transfer difference (DEEP‐STD) NMR, STD competition experiments, transfer‐NOESY, and Hamiltonian replica exchange molecular dynamics (HREMD) unveiled the presence of a novel subsite adjacent to the known subsites of GM1 on CTB. more...
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- 2020
32. Safety of anticoagulation in patients treated with urgent reperfusion for ischemic stroke related to atrial fibrillation
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Antonio Baldi, Licia Denti, Kennedy R. Lees, Nicola Mumoli, Panagiotis Halvatsiotis, Massimo Del Sette, Alberto Chiti, Peter Vanacker, Marta Bellesini, Tiziana Tassinari, Paolo Bovi, Alessandro Padovani, Christina Rueckert, Jessica Barlinn, Dorjan Zabzuni, Cataldo D'Amore, Loris Poli, Maria Luisa De Lodovici, Federica Letteri, Odysseas Kargiotis, Manuel Cappellari, Prasanna Tadi, Turgut Tatlisumak, Cecilia Becattini, Ludovica Anna Cimini, Liisa Tomppo, Yuriy Flomin, Giancarlo Agnelli, Aikaterini Theodorou, Serena Monaco, Elena Ferrari, Rossana Tassi, Monica Acciarresi, Patrik Michel, Alessio Pieroni, Enrico Maria Lotti, Michele Venti, Walter Ageno, Sung Il Sohn, Leonardo Ulivi, Maurizio Paciaroni, Konstantinos Vadikolias, Jukka Putaala, Cindy Tiseo, Valeria Caso, Alessandro Pezzini, Giorgio Silvestrelli, Alfonso Ciccone, Francesco Corea, Lilla Szabó, Francesca Guideri, Martina Giuntini, Gianni Lorenzini, Efstathia Karagkiozi, Davide Imberti, Luca Masotti, Azmil H. Abdul-Rahim, Theodore Karapanayiotides, Alessia Lanari, Andrea Alberti, Simona Marcheselli, Vieri Vannucchi, Giuseppe Martini, Shadi Yaghi, Marialuisa Zedde, Michela Giustozzi, Karen L. Furie, Danilo Toni, Chrissoula Liantinioti, Dirk Deleu, Franco Galati, Elisa Giorli, Monica Carletti, Vanessa Gourbali, Michelangelo Mancuso, George Ntaios, George Athanasakis, Fabio Bandini, Vera Volodina, Nicola Giannini, Umberto Scoditti, Mario Maimone Baronello, Boris Doronin, Simona Sacco, Maria Giulia Mosconi, Georgios Tsivgoulis, László Csiba, Alberto Rigatelli, Kristian Barlinn, Konstantinos Makaritsis, Maurizio Acampa, and Giovanni Orlandi more...
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Male ,anticoagulants ,medicine.medical_specialty ,medicine.medical_treatment ,Hemorrhage ,Brain Ischemia ,Dabigatran ,Brain ischemia ,Internal medicine ,80 and over ,medicine ,Humans ,atrial fibrillation ,Prospective Studies ,Prospective cohort study ,Blood Coagulation ,Stroke ,Aged ,thrombolytic therapy ,Aged, 80 and over ,Advanced and Specialized Nursing ,Rivaroxaban ,business.industry ,Warfarin ,Atrial fibrillation ,Thrombolysis ,Middle Aged ,medicine.disease ,secondary prevention ,thrombectomy ,Anticoagulants ,Atrial Fibrillation ,Female ,Reperfusion ,Thrombectomy ,Thrombolytic Therapy ,Treatment Outcome ,Cardiology ,Neurology (clinical) ,Human medicine ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Background and Purpose: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention. Methods: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non–Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either vitamin K antagonists or nonvitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features. Results: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50–1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53–2.02]). Conclusions: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation–related acute ischemic stroke, who started on oral anticoagulant. more...
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- 2020
33. Ischemic Stroke despite Oral Anticoagulant Therapy in Patients with Atrial Fibrillation
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David, Seiffge, Gian Marco De Marchis, Masatoshi, Koga, Maurizio, Paciaroni, Duncan, Wilson, Manuel, Cappellari, Kosmas, Macha, Georgios, Tsivgoulis, Gareth, Ambler, Shoji, Arihiro, Leo, H Bonati, Bruno, Bonetti, Bernd, Kallmünzer, Keith, W Muir, Paolo, Bovi, Henrik, Gensicke, Manabu, Inoue, Stefan, Schwab, Shadi, Yaghi, Martin, M Brown, Philippe, Lyrer, Masahito, Takagi, Monica, Acciarrese, Hans Rolf Jager, Alexandros, A Polymeris, Kazunori, Toyoda, Michele, Venti, Christopher, Traenka, Hiroshi, Yamagami, Andrea, Alberti, Sohei, Yoshimura, Valeria, Caso, Stefan, T Engelter, David, J Werring, Kenichi, Todo, Kazumi, Kimura, Kensaku, Shibazaki, Yoshiki, Yagita, Eisuke, Furui, Ryo, Itabashi, Tadashi, Terasaki, Yoshiaki, Shiokawa, Teruyuki, Hirano, Rieko, Suzuki, Kenji, Kamiyama, Jyoji, Nakagawara, Shunya, Takizawa, Kazunari, Homma, Satoshi, Okuda, Yasushi, Okada, Koichiro, Maeda, Tomoaki, Kameda, Kazuomi, Kario, Yoshinari, Nagakane, Yasuhiro, Hasegawa, Hisanao, Akiyama, Satoshi, Shibuya, Hiroshi, Mochizuki, Yasuhiro, Ito, Takahiro, Nakashima, Hideki, Matsuoka, Kazuhiro, Takamatsu, Kazutoshi, Nishiyama, Kanta, Tanaka, Kaoru, Endo, Tetsuya, Miyagi, Masato, Osaki, Junpei, Kobayashi, Takuya, Okata, Eijiro, Tanaka, Yuki, Sakamoto, Keisuke, Tokunaga, Hotake, Takizawa, Junji, Takasugi, Soichiro, Matsubara, Kyoko, Higashida, Takayuki, Matsuki, Naoto, Kinoshita, Masayuki, Shiozawa, Toshihiro, Ide, Takeshi, Yoshimoto, Daisuke, Ando, Kyohei, Fujita, Masaya, Kumamoto, Teppei, Kamimura, Muneaki, Kikuno, Tadataka, Mizoguchi, Takeo, Sato, Karen, L Furie, Prasanna, Tadi, Cecilia, Becattini, Nicola, Falocci, Marialuisa, Zedde, Azmil, H Abdul-Rahim, Kennedy, R Lees, Cataldo, D’Amore, Maria, G Mosconi, Ludovica, A Cimini, Monica, Carletti, Alberto, Rigatelli, Jukka, Putaala, Liisa, Tomppo, Turgut, Tatlisumak, Fabio, Bandini, Simona, Marcheselli, Alessandro, Pezzini, Loris, Poli, Alessandro, Padovani, Luca, Masotti, Vieri, Vannucchi, Sung-Il, Sohn, Gianni, Lorenzini, Rossana, Tassi, Francesca, Guideri, Maurizio, Acampa, Giuseppe, Martini, George, Ntaios, Efstathia, Karagkiozi, George, Athanasakis, Kostantinos, Makaritsis, Kostantinos, Vadikolias, Chrysoula, Liantinioti, Maria, Chondrogianni, Nicola, Mumoli, Domenico, Consoli, Franco, Galati, Simona, Sacco, Antonio, Carolei, Cindy, Tiseo, Francesco, Corea, Walter, Ageno, Marta, Bellesini, Giorgio, Silvestrelli, Alfonso, Ciccone, Umberto, Scoditti, Licia, Denti, Mancuso, Michelangelo, Miriam, Maccarrone, Orlandi, Giovanni, Nicola, Giannini, Gino, Gialdini, Tiziana, Tassinari, Maria Luisa De Lodovici, Giorgio, Bono, Christina, Rueckert, Antonio, Baldi, Danilo, Toni, Federica, Letteri, Martina, Giuntini, Enrico, M Lotti, Yuriy, Flomin, Alessio, Pieroni, Odysseas, Kargiotis, Theodore, Karapanayiotides, Serena, Monaco, Laszló, Csiba, Lilla, Szabó, Alberto, Chiti, Elisa, Giorli, Massimo Del Sette, Davide, Imberti, Dorjan, Zabzuni, Boris, Doronin, Vera, Volodina, Patrik, Michel, Peter, Vanacker, Kristian, Barlinn, Lars, P Pallesen, Ulf, Bodechtel, Leonardo, Ulivi, Dirk, Deleu, Gayane, Melikyan, Jessica, Bourlinn, Naveed, Akhar, Falsal, Ibrahin, Gourbali, Vanessa, Hawone, Baronello, Lisa, Hert, Nils, Peters, Marina, Maurer, and Martina, Wiegert more...
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0301 basic medicine ,medicine.medical_specialty ,Vascular disease ,business.industry ,Hazard ratio ,Ischemia ,610 Medicine & health ,Atrial fibrillation ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Neurology ,Interquartile range ,Internal medicine ,Heart failure ,medicine ,Neurology (clinical) ,Prospective cohort study ,business ,Stroke ,030217 neurology & neurosurgery ,Research Articles ,Research Article - Abstract
Objective:\ud It is not known whether patients with atrial fibrillation (AF) with ischemic stroke despite oral anticoagulant therapy are at increased risk for further recurrent strokes or how ongoing secondary prevention should be managed.\ud \ud Methods:\ud We conducted an individual patient data pooled analysis of 7 prospective cohort studies that recruited patients with AF and recent cerebral ischemia. We compared patients taking oral anticoagulants (vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC]) prior to index event (OACprior ) with those without prior oral anticoagulation (OACnaive ). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OACchanged ) with those who continued the same anticoagulation as secondary prevention (OACunchanged ). Time to recurrent acute ischemic stroke (AIS) was analyzed using multivariate competing risk Fine-Gray models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).\ud \ud Results:\ud We included 5,413 patients (median age = 78 years [interquartile range (IQR) = 71-84 years]; 5,136 [96.7%] had ischemic stroke as the index event, median National Institutes of Health Stroke Scale on admission = 6 [IQR = 2-12]). The median CHA2 DS2 -Vasc score (congestive heart failure, hypertension, age≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) was 5 (IQR = 4-6) and was similar for OACprior (n = 1,195) and OACnaive (n = 4,119, p = 0.103). During 6,128 patient-years of follow-up, 289 patients had AIS (4.7% per year, 95% CI = 4.2-5.3%). OACprior was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2-2.3, p = 0.005). OACchanged (n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7-2.1, p = 0.415) compared with OACunchanged (n = 585).\ud \ud Interpretation:\ud Patients with AF who have an ischemic stroke despite previous oral anticoagulation are at a higher risk for recurrent ischemic stroke despite a CHA2 DS2 -Vasc score similar to those without prior oral anticoagulation. Better prevention strategies are needed for this high-risk patient group. more...
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- 2019
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34. STD NMR as a Technique for Ligand Screening and Structural Studies
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Samuel, Walpole, Serena, Monaco, Ridvan, Nepravishta, and Jesus, Angulo
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Epitopes ,Binding Sites ,Magnetic Resonance Spectroscopy ,Naproxen ,Macromolecular Substances ,Humans ,Proteins ,Serum Albumin, Human ,Ligands ,Protein Binding - Abstract
STD NMR is a powerful ligand-based tool for screening small molecules and low molecular weight fragments for their interaction with a given macromolecule. Such information is invaluable both in the drug discovery sector and in understanding fundamental biological interactions. Recently, powerful methods have been developed to extract a greater wealth of information from the STD NMR experiment, including ligand binding epitopes, dissociation constant determination, and mapping of binding site properties. Herein we describe these STD NMR experiments, giving practical examples for each approach, and highlight the important parameters and common pitfalls that must be considered for a successful experiment. more...
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- 2019
35. STD NMR as a Technique for Ligand Screening and Structural Studies
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Ridvan Nepravishta, Samuel Walpole, Jesús Angulo, and Serena Monaco
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Dissociation constant ,Chemistry ,Drug discovery ,Binding site ,Ligand (biochemistry) ,Combinatorial chemistry ,Small molecule ,Epitope ,Macromolecule - Abstract
STD NMR is a powerful ligand-based tool for screening small molecules and low molecular weight fragments for their interaction with a given macromolecule. Such information is invaluable both in the drug discovery sector and in understanding fundamental biological interactions. Recently, powerful methods have been developed to extract a greater wealth of information from the STD NMR experiment, including ligand binding epitopes, dissociation constant determination, and mapping of binding site properties. Herein we describe these STD NMR experiments, giving practical examples for each approach, and highlight the important parameters and common pitfalls that must be considered for a successful experiment. more...
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- 2019
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36. Spatially Resolved STD-NMR Applied to the Study of Solute Transport in Biphasic Systems: Application to Protein-Ligand Interactions
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Juan C. Muñoz–García, Ridvan Nepravishta, Yaroslav Z. Khimyak, Jesús Angulo, Serena Monaco, and Universidad de Sevilla. Departamento de Química orgánica
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Pharmacology ,010405 organic chemistry ,Chemistry ,SR-STD NMR ,Spatially resolved ,Plant Science ,General Medicine ,Nuclear magnetic resonance spectroscopy ,Interface ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,Magnetization ,Complementary and alternative medicine ,Chemical physics ,Phase (matter) ,Drug Discovery ,Proton NMR ,Diffusion (business) ,Saturation (chemistry) ,1 H-NMR ,Biphasic system ,CEST ,Protein ligand - Abstract
Fluid biphasic systems are one of the most interesting dynamic systems in chemistry and biochemistry. In nuclear magnetic resonance (NMR) spectroscopy, the study of the solute dynamics across fluid biphasic systems requires the introduction of dedicated NMR methods, due to their intrinsic heterogeneity. Diffusion and spatially resolved NMR techniques represent a useful approach for dealing with the study of solutes in biphasic systems and have been applied lately with success. Nevertheless, other potential applications of NMR spectroscopy for biphasic systems remain to be explored. In this proof of-concept communication, we specifically aimed to investigate whether solute exchange between two immiscible phases can be followed by NMR experiments involving transfer of magnetization. To that aim, we have used spatially resolved saturation transfer difference NMR (SR-STD NMR) experiments to analyze solute exchange by transfer of saturation from one phase to the other in a biphasic system and have explored which are the underlying mechanisms leading to the transfer of magnetization between phases and the limits of the approach. We hereby demonstrate that SR-STD NMR is feasible and that it might be implemented in pharmacological screening for binders of biological receptors or in the study of chemical and biochemical reactions occurring at interfaces. more...
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- 2019
37. Early recurrence in paroxysmal versus sustained atrial fibrillation in patients with acute ischaemic stroke
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Karen L. Furie, Franco Galati, Antonio Carolei, Simona Sacco, Naveed Akhtar, Andrea Alberti, Vanessa Gourbali, Elisa Giorli, Federica Letteri, Filippo Angelini, Georgios Tsivgoulis, Simona Marcheselli, L.-P. Pallesen, Nicola Falocci, Serena Monaco, Giovanni Orlandi, Maria Luisa De Lodovici, Maria Giulia Mosconi, Michele Venti, Walter Ageno, Mario Maimone Baronello, László Csiba, Alfonso Ciccone, Odysseas Kargiotis, Kostantinos Vadikolias, Massimo Del Sette, Chrysoula Liantinioti, Maurizio Paciaroni, Valeria Caso, Cecilia Becattini, Danilo Toni, Peter Vanacker, Alessandro Padovani, Azmil H. Abdul-Rahim, Gino Gialdini, Christina Rueckert, Patrik Michel Pd-Mer, Giorgio Silvestrelli, Marialuisa Zedde, Cataldo D'Amore, Sung Il Sohn, Monica Acciarresi, Monica Carletti, George Ntaios, Kennedy R. Lees, Maria Chondrogianni, Gayane Melikyan, Domenico Consoli, Faisal Ibrahim, Francesca Guideri, Martina Giuntini, Alessandro Pezzini, Fabio Bandini, Vera Volodina, Alberto Rigatelli, Kristian Barlinn, Luca Masotti, Licia Denti, Boris Doronin, Tiziana Tassinari, Cindy Tiseo, Dorjan Zabzuni, Alberto Chiti, Francesco Corea, Nicola Giannini, Loris Poli, Nicola Mumoli, Jessica Kepplinger, Maurizio Acampa, Riccardo Altavilla, George Athanasakis, Theodore Karapanayiotides, Antonio Baldi, Prasanna Tadi, Umberto Scoditti, Turgut Tatlisumak, Yuriy Flomin, Rossana Tassi, Michelangelo Mancuso, Liisa Tomppo, Vieri Vannucchi, Efstathia Karagkiozi, Davide Imberti, Enrico Maria Lotti, Alessio Pieroni, Lilla Szabó, Dirk Deleu, Giancarlo Agnelli, Giorgio Bono, Miriam Maccarrone, Jukka Putaala, Giuseppe Martini, Marta Bellesini, Shadi Yaghi, Ludovica Anna Cimini, Gianni Lorenzini, K. Makaritsis, Paolo Bovi, Manuel Cappellari, HUS Neurocenter, Department of Neurosciences, Neurologian yksikkö, and University of Helsinki more...
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medicine.medical_specialty ,ANTICOAGULATED PATIENTS ,anticoagulation ,atrial fibrillation ,paroxysmal atrial fibrillation ,Stroke ,stroke recurrence ,sustained atrial fibrillation ,Early Recurrence ,Paroxysmal atrial fibrillation ,Stroke recurrence ,macromolecular substances ,030204 cardiovascular system & hematology ,3124 Neurology and psychiatry ,EVENTS ,03 medical and health sciences ,PERSISTENT ,0302 clinical medicine ,Original Research Articles ,Internal medicine ,Ischaemic stroke ,medicine ,ORAL ANTICOAGULATION ,In patient ,cardiovascular diseases ,Prospective cohort study ,OUTCOMES ,business.industry ,DEATH ,3112 Neurosciences ,Atrial fibrillation ,medicine.disease ,PATTERN ,Cardiology ,cardiovascular system ,Human medicine ,Neurology (clinical) ,HIGHER RISK ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery - Abstract
Background The relationship between different patterns of atrial fibrillation and early recurrence after an acute ischaemic stroke is unclear. Purpose In a prospective cohort study, we evaluated the rates of early ischaemic recurrence after an acute ischaemic stroke in patients with paroxysmal atrial fibrillation or sustained atrial fibrillation which included persistent and permanent atrial fibrillation. Methods In patients with acute ischaemic stroke, atrial fibrillation was categorised as paroxysmal atrial fibrillation or sustained atrial fibrillation. Ischaemic recurrences were the composite of ischaemic stroke, transient ischaemic attack and symptomatic systemic embolism occurring within 90 days from acute index stroke. Results A total of 2150 patients (1155 females, 53.7%) were enrolled: 930 (43.3%) had paroxysmal atrial fibrillation and 1220 (56.7%) sustained atrial fibrillation. During the 90-day follow-up, 111 ischaemic recurrences were observed in 107 patients: 31 in patients with paroxysmal atrial fibrillation (3.3%) and 76 with sustained atrial fibrillation (6.2%) (hazard ratio (HR) 1.86 (95% CI 1.24–2.81)). Patients with sustained atrial fibrillation were on average older, more likely to have diabetes mellitus, hypertension, history of stroke/ transient ischaemic attack, congestive heart failure, atrial enlargement, high baseline NIHSS-score and implanted pacemaker. After adjustment by Cox proportional hazard model, sustained atrial fibrillation was not associated with early ischaemic recurrences (adjusted HR 1.23 (95% CI 0.74–2.04)). Conclusions After acute ischaemic stroke, patients with sustained atrial fibrillation had a higher rate of early ischaemic recurrence than patients with paroxysmal atrial fibrillation. After adjustment for relevant risk factors, sustained atrial fibrillation was not associated with a significantly higher risk of recurrence, thus suggesting that the risk profile associated with atrial fibrillation, rather than its pattern, is determinant for recurrence. more...
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- 2019
38. Anticoagulation After Stroke in Patients With Atrial Fibrillation
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Riccardo, Altavilla, Valeria, Caso, Fabio, Bandini, Giancarlo, Agnelli, Georgios, Tsivgoulis, Shadi, Yaghi, Karen L, Furie, Prasanna, Tadi, Cecilia, Becattini, Marialuisa, Zedde, Azmil H, Abdul-Rahim, Kennedy R, Lees, Andrea, Alberti, Michele, Venti, Monica, Acciarresi, Cataldo, D'Amore, Maria Giulia, Mosconi, Ludovica, Anna Cimini, Jessica, Fusaro, Paolo, Bovi, Monica, Carletti, Alberto, Rigatelli, Manuel, Cappellari, Jukka, Putaala, Liisa, Tomppo, Turgut, Tatlisumak, Simona, Marcheselli, Alessandro, Pezzini, Loris, Poli, Alessandro, Padovani, Luca, Masotti, Vieri, Vannucchi, Sung-Il, Sohn, Gianni, Lorenzini, Rossana, Tassi, Francesca, Guideri, Maurizio, Acampa, Giuseppe, Martini, George, Ntaios, George, Athanasakis, Konstantinos, Makaritsis, Efstathia, Karagkiozi, Konstantinos, Vadikolias, Chrysoula, Liantinioti, Maria, Chondrogianni, Nicola, Mumoli, Domenico, Consoli, Franco, Galati, Simona, Sacco, Antonio, Carolei, Cindy, Tiseo, Francesco, Corea, Walter, Ageno, Marta, Bellesini, Giorgio, Silvestrelli, Alfonso, Ciccone, Alessia, Lanari, Umberto, Scoditti, Licia, Denti, Michelangelo, Mancuso, Miriam, Maccarrone, Leonardo, Ulivi, Giovanni, Orlandi, Nicola, Giannini, Gino, Gialdini, Tiziana, Tassinari, Maria Luisa, De Lodovici, Giorgio, Bono, Christina, Rueckert, Antonio, Baldi, Sebastiano, D'Anna, Danilo, Toni, Federica, Letteri, Martina, Giuntini, Enrico, Maria Lotti, Yuriy, Flomin, Alessio, Pieroni, Odysseas, Kargiotis, Theodore, Karapanayiotides, Serena, Monaco, Mario, Maimone Baronello, Laszló, Csiba, Lilla, Szabó, Alberto, Chiti, Elisa, Giorli, Massimo, Del Sette, Davide, Imberti, Dorjan, Zabzuni, Boris, Doronin, Vera, Volodina, Patrik, Michel, Peter, Vanacker, Kristian, Barlinn, Lars-Peder, Pallesen, Jessica, Barlinn, Dirk, Deleu, Gayane, Melikyan, Faisal, Ibrahim, Naveed, Akhtar, Vanessa, Gourbali, and Maurizio, Paciaroni more...
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Stroke ,anticoagulants ,atrial fibrillation ,humans ,incidence ,secondary prevention ,Heparin, Low-Molecular-Weight ,Cerebral Hemorrhage - Abstract
Background and Purpose- Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods- We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results- Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P0.0001), as well as ischemic (odds ratio, 2.2; 95% CI, 1.3-3.9; P=0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2-4.9; P=0.01) end points separately. Conclusions- Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients. more...
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- 2019
39. Structural basis for arginine glycosylation of host substrates by bacterial effector proteins
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Hyun Soo Cho, Sung Hoon Jun, Samuel Walpole, Jin Won Cho, Miaomiao Wu, Ramon Hurtado-Guerrero, Jesús Angulo, Young Hun Kim, Ana García-García, Ju-yeon Kim, J.B. Park, Jeon Soo Shin, Serena Monaco, Michael P. Hays, Youngki Yoo, Samir El Qaidi, Philip R. Hardwidge, National Research Foundation of Korea, Government of South Korea, and University of East Anglia more...
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Salmonella typhimurium ,0301 basic medicine ,Glycosylation ,Arginine ,Virulence Factors ,Science ,General Physics and Astronomy ,Molecular Dynamics Simulation ,Crystallography, X-Ray ,010402 general chemistry ,01 natural sciences ,Article ,General Biochemistry, Genetics and Molecular Biology ,Acetylglucosamine ,Substrate Specificity ,Enzyme catalysis ,03 medical and health sciences ,chemistry.chemical_compound ,Bacterial Proteins ,Catalytic Domain ,Glycosyltransferase ,Animals ,Humans ,Transferase ,lcsh:Science ,Nuclear Magnetic Resonance, Biomolecular ,2. Zero hunger ,chemistry.chemical_classification ,Mice, Inbred BALB C ,Multidisciplinary ,biology ,Effector ,Escherichia coli Proteins ,Active site ,General Chemistry ,3. Good health ,0104 chemical sciences ,HEK293 Cells ,030104 developmental biology ,Enzyme ,chemistry ,Biochemistry ,Host-Pathogen Interactions ,biology.protein ,Female ,lcsh:Q - Abstract
15 pags, 5 figs, The bacterial effector proteins SseK and NleB glycosylate host proteins on arginine residues, leading to reduced NF-κB-dependent responses to infection. Salmonella SseK1 and SseK2 are E. coli NleB1 orthologs that behave as NleB1-like GTs, although they differ in protein substrate specificity. Here we report that these enzymes are retaining glycosyltransferases composed of a helix-loop-helix (HLH) domain, a lid domain, and a catalytic domain. A conserved HEN motif (His-Glu-Asn) in the active site is important for enzyme catalysis and bacterial virulence. We observe differences between SseK1 and SseK2 in interactions with substrates and identify substrate residues that are critical for enzyme recognition. Long Molecular Dynamics simulations suggest that the HLH domain determines substrate specificity and the lid-domain regulates the opening of the active site. Overall, our data suggest a front-face Si mechanism, explain differences in activities among these effectors, and have implications for future drug development against enteric pathogens., This work was supported by Grants from the National Research Foundation of Korea (NRF) funded by the Korean government (MEST) (NRF- 2016R1A2B2013305, 2016R1A5A1010764, 2014R1A4A1008625, 2017M3A9F6029755 and 2017R1A2B3006704), the Strategic Initiative for Microbiomes in Agriculture and Food funded by Ministry of Agriculture, Food and Rural Affairs (918012-4) and Brain Korea 21 PLUS Project for Medical Science. This work was also supported by Grants AI093913 and AI127973 from the National Institutes of Health (to P.R.H.). We also thank ARAID and MEC (CTQ2013-44367-C2-2-P, BFU2016-75633-P to R.H-G.), and the DGA (group number E34_R17) for financial support. S.M. acknowledges a postgraduate studentship from the School of Pharmacy of the University of East Anglia. J.A. and S W. acknowledge funding from BBSRC through a research grant (BB/P010660/1) and a DTP PhD studentship, respectively. more...
- Published
- 2018
40. Unravelling the specificity and mechanism of sialic acid recognition by the gut symbiont Ruminococcus gnavus
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Tanja Šuligoj, Serena Monaco, Louise E. Tailford, Xi Chen, Ajit Varki, John Walshaw, Hai Yu, C. David Owen, Romane Lallement, Jesús Angulo, Laura Vaux, Sandra Tribolo, Garry L. Taylor, Zahra Khedri, Andrew Bell, Karine Lecointe, Nathalie Juge, Marc Horrex, Universidad de Sevilla. Departamento de Química orgánica, University of St Andrews. Office of the Principal, University of St Andrews. School of Biology, and University of St Andrews. Biomedical Sciences Research Complex more...
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0301 basic medicine ,QH301 Biology ,General Physics and Astronomy ,Lactose ,Plasma protein binding ,Inbred C57BL ,Crystallography, X-Ray ,Substrate Specificity ,chemistry.chemical_compound ,Mice ,Ruminococcus gnavus ,Catalytic Domain ,Ruminococcus ,Site-Directed ,QD ,lcsh:Science ,Multidisciplinary ,Crystallography ,biology ,Chemistry ,Bacterial ,Adhesins ,3. Good health ,Biochemistry ,Goblet Cells ,Protein Binding ,Glycan ,Colon ,Science ,Neuraminidase ,R Medicine ,General Biochemistry, Genetics and Molecular Biology ,Article ,Bacterial genetics ,Cell Line ,03 medical and health sciences ,QH301 ,Animals ,Humans ,Adhesins, Bacterial ,Symbiosis ,Glycoproteins ,030102 biochemistry & molecular biology ,Mucin ,Mucins ,Computational Biology ,DAS ,General Chemistry ,QD Chemistry ,Mucus ,N-Acetylneuraminic Acid ,Sialic acid ,Bacterial adhesin ,Mice, Inbred C57BL ,030104 developmental biology ,Mutagenesis ,biology.protein ,X-Ray ,Mutagenesis, Site-Directed ,lcsh:Q - Abstract
Ruminococcus gnavus is a human gut symbiont wherein the ability to degrade mucins is mediated by an intramolecular trans-sialidase (RgNanH). RgNanH comprises a GH33 catalytic domain and a sialic acid-binding carbohydrate-binding module (CBM40). Here we used glycan arrays, STD NMR, X-ray crystallography, mutagenesis and binding assays to determine the structure and function of RgNanH_CBM40 (RgCBM40). RgCBM40 displays the canonical CBM40 β-sandwich fold and broad specificity towards sialoglycans with millimolar binding affinity towards α2,3- or α2,6-sialyllactose. RgCBM40 binds to mucus produced by goblet cells and to purified mucins, providing direct evidence for a CBM40 as a novel bacterial mucus adhesin. Bioinformatics data show that RgCBM40 canonical type domains are widespread among Firmicutes. Furthermore, binding of R. gnavus ATCC 29149 to intestinal mucus is sialic acid mediated. Together, this study reveals novel features of CBMs which may contribute to the biogeography of symbiotic bacteria in the gut., The mucus layer is an important physical niche within the gut which harbours a distinct microbial community. Here the authors show that specific carbohydrate-binding modules associated with bacterial carbohydrate-active enzymes are mucus adhesins that target regions of the distal colon rich in sialomucins. more...
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- 2017
41. Differential epitope mapping by STD NMR spectroscopy to reveal the nature of protein–ligand contacts
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Nathalie Juge, Serena Monaco, Jesús Angulo, and Louise E. Tailford
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Binding Sites ,010405 organic chemistry ,Chemistry ,Stereochemistry ,Communication ,Proteins ,General Medicine ,Nuclear magnetic resonance spectroscopy ,Ligands ,010402 general chemistry ,fragment-based drug design ,01 natural sciences ,Communications ,0104 chemical sciences ,epitope mapping ,NMR spectroscopy ,protein–ligand binding ,Epitope mapping ,Protein–Ligand Interactions ,pharmacophores ,Nuclear Magnetic Resonance, Biomolecular ,Differential (mathematics) ,Protein ligand - Abstract
Saturation transfer difference (STD) NMR spectroscopy is extensively used to obtain epitope maps of ligands binding to protein receptors, thereby revealing structural details of the interaction, which is key to direct lead optimization efforts in drug discovery. However, it does not give information about the nature of the amino acids surrounding the ligand in the binding pocket. Herein, we report the development of the novel method differential epitope mapping by STD NMR (DEEP‐STD NMR) for identifying the type of protein residues contacting the ligand. The method produces differential epitope maps through 1) differential frequency STD NMR and/or 2) differential solvent (D2O/H2O) STD NMR experiments. The two approaches provide different complementary information on the binding pocket. We demonstrate that DEEP‐STD NMR can be used to readily obtain pharmacophore information on the protein. Furthermore, if the 3D structure of the protein is known, this information also helps in orienting the ligand in the binding pocket. more...
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- 2017
42. Prestroke CHA2DS2-VASc Score and Severity of Acute Stroke in Patients with Atrial Fibrillation: Findings from RAF Study
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Umberto Scoditti, Suzette Remillard, Maria Giulia Mosconi, Serena Monaco, Giancarlo Agnelli, Maurizio Paciaroni, Dorjan Zabzuni, Boris Doronin, Giorgio Bono, Simona Sacco, Ulf Bodechtel, Simona Marcheselli, Maria Luisa De Lodovici, Kennedy R. Lees, Alessio Pieroni, Lilla Szabó, Gianni Lorenzini, Cecilia Becattini, Nicola Falocci, Tiziana Tassinari, Jukka Putaala, Peter Vanacker, László Csiba, Giovanni Orlandi, Maria Cordier, Giuseppe Martini, Danilo Toni, Domenico Consoli, Christina Rueckert, Davide Imberti, Chrissoula Liantinioti, Monica Acciarresi, Paolo Costa, Sung Il Sohn, Monica Carletti, Dirk Deleu, Johannes Gerber, Francesca Guideri, Paolo Bovi, Rossana Tassi, Luca Masotti, Alberto Chiti, Licia Denti, Valeria Caso, Georgios Tsivgoulis, Antonio Baldi, Naveed Akhtar, Massimo Del Sette, Alberto Rigatelli, Kristian Barlinn, Cindy Tiseo, Franco Galati, Antonio Carolei, Andrea Morotti, Alessandro Pezzini, Francesco Corea, Patrik Michel, Vera Volodina, Cataldo D'Amore, Lars-Peder Pallesen, Andrea Alberti, Faisal Ibrahim, Mario Maimone Baronello, Jessica Kepplinger, Sebastiano D'Anna, Azmil H. Abdul-Rahim, Michele Venti, Walter Ageno, Gino Gialdini, Kostantinos Vadikolias, Gayane Melikyan, Turgut Tatlisumak, Alessandro Padovani, Neurologian yksikkö, Department of Neurosciences, Clinicum, University of Helsinki, and HUS Neurocenter more...
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Male ,atrial fibrillation ,CHA ,2 ,DS ,VASc score ,Ischemic stroke ,outcome ,scores ,severity ,Aged ,Aged, 80 and over ,Area Under Curve ,Asia ,Atrial Fibrillation ,Chi-Square Distribution ,Disability Evaluation ,Europe ,Female ,Humans ,Linear Models ,Logistic Models ,Magnetic Resonance Imaging ,Multivariate Analysis ,Odds Ratio ,Predictive Value of Tests ,Prognosis ,Prospective Studies ,ROC Curve ,Risk Assessment ,Risk Factors ,Severity of Illness Index ,Stroke ,Time Factors ,Tomography, X-Ray Computed ,Decision Support Techniques ,CHA2DS2-VASc score ,Surgery ,Rehabilitation ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,ARTERIAL TERRITORIES ,030204 cardiovascular system & hematology ,Logistic regression ,CHADS(2) ,3124 Neurology and psychiatry ,0302 clinical medicine ,Modified Rankin Scale ,80 and over ,Medicine ,Elméleti orvostudományok ,ACUTE ISCHEMIC-STROKE ,Prospective cohort study ,Tomography ,OUTCOMES ,Area under the curve ,Atrial fibrillation ,Orvostudományok ,HUMAN BRAIN ,X-Ray Computed ,CHA(2)DS(2)-VASc score ,Cardiology ,medicine.medical_specialty ,education ,macromolecular substances ,03 medical and health sciences ,Internal medicine ,cardiovascular diseases ,ischemic stroke ,surgery ,rehabilitation ,neurology (clinical) ,cardiology and cardiovascular medicine ,Receiver operating characteristic ,business.industry ,3112 Neurosciences ,medicine.disease ,3121 General medicine, internal medicine and other clinical medicine ,CHA2DS2–VASc score ,Physical therapy ,Human medicine ,business ,030217 neurology & neurosurgery - Abstract
Background and Purpose: The aim of this study was to investigate for a possible association between both prestroke CHA(2)DS(2)-VASc score and the severity of stroke at presentation, as well as disability and mortality at 90 days, in patients with acute stroke and atrial fibrillation (AF). Methods: This prospective study enrolled consecutive patients with acute ischemic stroke, AF, and assessment of prestroke CHA2DS2-VASc score. Severity of stroke was assessed on admission using the National Institutes of Health Stroke Scale (NIHSS) score (severe stroke: NIHSS >= 10). Disability and mortality at 90 days were assessed by the modified Rankin Scale (mRS = 3). Multiple logistic regression was used to correlate prestroke CHA(2)DS(2)-VASc and severity of stroke, as well as disability and mortality at 90 days. Results: Of the 1020 patients included in the analysis, 606 patients had an admission NIHSS score lower and 414 patients higher than 10. At 90 days, 510 patients had mRS >= 3. A linear correlation was found between the prestroke CHA(2)DS(2)-VASc score and severity of stroke (P = .001). On multivariate analysis, CHA(2)DS(2)-VASc score correlated with severity of stroke (P = .041) and adverse functional outcome (mRS = 3) (P = .001). A logistic regression with the receiver operating characteristic graph procedure (C-statistics) evidenced an area under the curve of .60 (P = .0001) for severe stroke. Furthermore, a correlation was found between prestroke CHA(2)DS(2)-VASc score and lesion size. Conclusions: In patients with AF, in addition to the risk of stroke, a high CHA(2)DS(2)-VASc score was independently associated with both stroke severity at onset and disability and mortality at 90 days. more...
- Published
- 2017
43. Myocardial Infarction Following Intravenous Thrombolysis for Acute Ischemic Stroke: Case Report and Literature Review
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Serena Monaco, Melchiorre Gilberto Cellura, Matilde Gammino, Marina Mannino, Salvatore Asciutto, and Valeria Terruso
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medicine.medical_specialty ,medicine.medical_treatment ,Embolism ,Anterior myocardial infarction ,030204 cardiovascular system & hematology ,Brain Ischemia ,03 medical and health sciences ,0302 clinical medicine ,Fatal Outcome ,Fibrinolytic Agents ,Internal medicine ,Medicine ,Humans ,Thrombolytic Therapy ,cardiovascular diseases ,Myocardial infarction ,Infusions, Intravenous ,Acute ischemic stroke ,Stroke ,Anterior Wall Myocardial Infarction ,Aged ,business.industry ,Rehabilitation ,Thrombolysis ,medicine.disease ,Tissue Plasminogen Activator ,Cardiology ,Surgery ,Female ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery - Abstract
Embolic complications of intravenous thrombolysis for acute ischemic stroke are increasingly recognized, and to date several cases of myocardial infarction soon after the administration of alteplase have been reported. We describe a case of early anterior myocardial infarction during intravenous thrombolysis for stroke and review the current literature. more...
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- 2016
44. Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients With Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema: The ALESSA Score Study
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Francesca Guideri, Martina Giuntini, Luca Masotti, Alessandro Padovani, Danilo Toni, Maria Chondrogianni, Monica Carletti, Cecilia Becattini, Dorjan Zabzuni, Loris Poli, Theodore Karapanayiotides, Monica Acciarresi, Antonio Procopio, Giuseppe Martini, Giovanni Orlandi, Maurizio Acampa, Nicola Falocci, Vieri Vannucchi, Valeria Caso, Cindy Tiseo, Enrico Maria Lotti, László Csiba, Giancarlo Agnelli, Michelangelo Mancuso, Giorgio Bono, Lilla Szabó, Antonio Baldi, Serena Monaco, Jukka Putaala, Faisal Ibrahim, Dirk Deleu, Prasanna Tadi, Yuriy Flomin, Miriam Maccarrone, Georgios Tsivgoulis, Kennedy R. Lees, George Ntaios, Massimo Del Sette, Alberto Rigatelli, Kristian Barlinn, Naveed Akhtar, Jessica Kepplinger, Simona Sacco, Fabio Bandini, Vera Volodina, Lars-Peder Pallesen, Rossana Tassi, Odysseas Kargiotis, Peter Vanacker, Tiziana Tassinari, Nicola Giannini, Christina Rueckert, Ulf Bodechtel, Elisa Giorli, Simona Marcheselli, Efstathia Karagkiozi, Davide Imberti, Michele Venti, Walter Ageno, Chrysoula Liantinioti, Kostantinos Vadikolias, Alfonso Ciccone, Federica Letteri, Domenico Consoli, Andrea Alberti, Turgut Tatlisumak, Marialuisa Zedde, Vanessa Gourbali, Alberto Chiti, Manuel Cappellari, Cataldo D'Amore, Alessandro Pezzini, Francesco Corea, Maurizio Paciaroni, Liisa Tomppo, Giorgio Silvestrelli, Gayane Melikyan, Gianni Lorenzini, K. Makaritsis, Paolo Bovi, Marta Bellesini, Patrik Michel, Ludovica Anna Cimini, Alessio Pieroni, Shadi Yaghi, Sebastiano D'Anna, Azmil H. Abdul-Rahim, Gino Gialdini, Licia Denti, Nicola Mumoli, Mario Maimone Baronello, Maria Luisa De Lodovici, Sung Il Sohn, Johannes Gerber, Giovanna Colombo, Boris Doronin, Karen L. Furie, Franco Galati, Antonio Carolei, Maria Giulia Mosconi, George Athanasakis, and Umberto Scoditti more...
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Male ,medicine.medical_specialty ,atrial fibrillation ,myocardial infarction ,risk stratification ,stroke ,Hemorrhage ,030204 cardiovascular system & hematology ,Risk Assessment ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Internal medicine ,Thromboembolism ,Atrial Fibrillation ,80 and over ,Medicine ,Humans ,Myocardial infarction ,Aged ,Aged, 80 and over ,Anticoagulants ,Female ,Ischemic Attack, Transient ,Prospective Studies ,Stroke ,Warfarin ,Prospective cohort study ,Advanced and Specialized Nursing ,business.industry ,Ischemic Attack ,Transient ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,atrial fibrillation, myocardial infarction, risk stratification, stroke ,Atrial fibrillation ,medicine.disease ,Cardiology ,Observational study ,Human medicine ,business ,Risk assessment ,Complication ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background and Purposes— This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods— The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00–1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08–2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P =0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30–1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632–0.763; P =0.0001) for ischemic outcome events and 0.585 (0.493–0.678; P =0.10) for major bleedings. Results— The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529–0.763; P =0.009) for ischemic outcome events and 0.407 (0.275–0.540; P =0.14) for hemorrhagic outcome events. Conclusions— In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings. more...
- Published
- 2016
45. Mechanical Thrombectomy of Acute Basilar Artery Occlusion: Single Center Experience
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Andrea Giorgianni, Federico Carimati, Maria Luisa De Lodovici, Giuseppe Craparo, Fabio Baruzzi, Alberto Terrana, Irene Chiara De Bernardi, Serena Monaco, Camilla Micieli, Carlo Pellegrino, and Cristina Gallo more...
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medicine.medical_specialty ,Cerebral infarction ,business.industry ,medicine.medical_treatment ,Mortality rate ,Stent ,Thrombolysis ,Single Center ,medicine.disease ,030218 nuclear medicine & medical imaging ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,Modified Rankin Scale ,Occlusion ,medicine ,business ,Survival rate ,030217 neurology & neurosurgery - Abstract
Purpose: Acute basilar artery occlusion (BAO) is a devastating neurological condition associated with a poor clinical outcome and a high mortality rate. Mechanical thrombectomy using a retrievable stent applied shortly after symptom onset could increase a good functional outcome, improving survival rate in patients with acute BAO. First clinical trials using stent retrievers have shown promising high recanalization rates. This study aimed to evaluate the feasibility, safety and efficacy of mechanical thrombectomy. Material and Methods: Seven consecutive patients (2 female, 5 male) with a mean age of 59,4 (range 40-82) with acute BAO undergone to endovascular therapy: all patients were treated with mechanical thrombectomy using a retrievable stent (in 5 patients with Solitaire-Covidien system, in 2 patients Revive-Codman system); two of these received in addition a intra-arterial thrombolysis (IAT), one was additionally treated with intra-venous thrombolysis (IVT). Successful recanalization was defined as Thrombolysis in Cerebral Infarction (TICI) grade 2b or 3. Good outcome was defined as modified Rankin Scale (mRS) score of 0–2 at 3 months. Results: Median NIHSS score at onset was 15,8 (range 12-22).Median procedure time to maximal recanalization was 72 minutes (range 35-135).Recanalization was achieved in 100% (7/7) of patients. One symptomatic parenchymal hemorrhage occurred in a patient treated additionally with intra-arterial thrombolysis. Median NIHSS score at 7 days from treatment was 7,2 (range 0-20). At 3 months a good outcome (mRS 0–2) was observed in 71,4% (5/7); overall mortality at 3 months was 28,6% (2/7). Conclusion: Mechanical thrombectomy in BAO presents high recanalization rate, with a very low complication rate, improving good outcome and survival rates in patients with BAO. more...
- Published
- 2016
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46. Contents Vol. 34, 2012
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Toshiho Ohtsuki, Druck Reinhardt Druck Basel, Alessandro Pezzini, Danilo Toni, Stephen Meairs, Karin Ernstrom, Hisashi Masugata, Simon Jung, S. Domènech, Heinrich Mattle, Valeria Caso, Luca Remonda, Giovanni Orlandi, Katsuhiko Matsuo, Takeshi Aoki, Randolph S. Marshall, Michael G. Hennerici, Joanna M. Wardlaw, Hiroaki Dobashi, Akira Ogawa, Xin Wang, Hidetoshi Matsukawa, Yasushi Okada, Mauro Silvestrini, Gino Gialdini, Oliver Findling, Manuel Cappellari, Koji Murao, Hideki Origasa, Eric Jouvent, Russell V. Luepker, Naoki Nakayama, A. Dávalos, Takanari Kitazono, Masakazu Kobayashi, Kazushi Deguchi, Marco Duering, Nassira Allili, Patrizia Nencini, Karen C. Albright, P. Cuadras, Andrea Zini, Dawn M Meyer, Alexander Karameshev, David Rodriguez-Luna, Alessandro Padovani, Osamu Yasuda, Alessio Pieroni, David S Liebeskind, Brett C. Meyer, Giorgio Bono, Yuichi Izumi, Ekkehart Jenetzky, Carlo Ferrarese, Francesca M Chappell, Claudia Trentini, Giampiero Galletti, Kenji Yoshida, Werner Hacke, Hiroyuki Imamura, Sean I Savitz, Joseph P. Broderick, Masahito Katoh, Marcia Spindler, Ivânia Alves, David C. Anderson, Naohisa Hosomi, Michele Venti, Markus A Möhlenbruch, Ming Yao, Falk Mueller-Riemenschneider, Saqib A Chaudhry, Wondwossen G Tekle, E. López-Cancio, Rakesh Khatri, José Alvarez-Sabín, Tiziana Tassinari, Takenori Yamaguchi, Hiroki Kuroda, Rossana Tassi, Timolaos Rizos, José G. Merino, Kohsuke Kudo, Gerhard Schroth, Carole Stuker, Marc Ribó, Cataldo D’Amore, Atsushi Murakata, Maria del C. Valdés Hernández, Carlos Veira, Kiyohiro Houkin, Tomohisa Nezu, M. Millán, Masahiro Kamouchi, Toshimitsu Aida, Christoph Gumbinger, Luis Ruano, Kuniaki Ogasawara, Takeo Abumiya, Julie Staals, Rema Raman, Roland Veltkamp, Gian Marco De Marchis, Stefan N. Willich, Alfonso Ciccone, Andria L. Ford, Hirofumi Soejima, Masayasu Matsumoto, Adnan I Qureshi, Àngels Pedragosa, Hisao Ogawa, Makoto Sasaki, Albert W Tsai, Caroline M. J. Loos, Joan Brugués, Motoharu Fujii, Masaki Shinoda, A. Massuet, Olga Maisterra, Maria Luisa DeLodovici, Shiro Aoki, Junko Tanaka, Alessia Lanari, Andrea Alberti, Osamu Takahashi, M. Gomis, Fergus N. Doubal, Satz Mengensatzproduktion, Rudolf Luedi, Hideo Ohyama, Shunrou Fujiwara, Krassen Nedeltchev, Giancarlo Agnelli, Andrei V. Alexandrov, Paolo Frigio Nichelli, Sheryl Martin-Schild, Isabel Araújo, Marta Rubiera, M. Hernández-Pérez, Marie-Luise Mono, Ameer E Hassan, Ximena Castillo, Paolo Bovi, Emilio Luda, Massimo Del Sette, Martin Dichgans, C. Berthet, Paolo Previdi, Robert J. van Oostenbrugge, Vítor Tedim Cruz, Maurizio Riva, Dawn Kleindorfer, Taro Suzuki, Naoko Kumagai, Noriko Ichihara, N. Pérez de la Ossa, Rui Barreto, Peter A. Ringleb, Mascia Nesi, Solveig Horstmann, Domenico Consoli, Domenico Inzitari, Alberto Chiti, Marcel Arnold, Natalia S. Rost, Giuseppe Martini, Carlos A. Molina, Stephan Rieks, Takuya Moriwaki, Kamakshi Lakshminarayan, Raffaella Cerqua, Maurizio Paciaroni, Lorenz Hirt, Claus Kiefer, Marwan El-Koussy, Elisabetta Traverso, Hideaki Nishimoto, Masakazu Kohno, Simone Beretta, Dominique Hervé, Johannes Slotboom, Ryoichi Ishikawa, Masami Yoshino, Giorgio Silvestrelli, Pierre J. Magistretti, Serena Monaco, Aekaterini Galimanis, Monica Acciarresi, James M. Peacock, L. Dorado, Simona Marcheselli, Hugues Chabriat, and Takamasa Nanba more...
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Neurology ,Traditional medicine ,business.industry ,Medicine ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business - Published
- 2012
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47. Plasma levels of inflammatory and thrombotic/fibrinolytic markers in acute ischemic strokes: Relationship with TOAST subtype, outcome and infarct site
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Giuseppe Licata, Antonia Serio, Antonino Tuttolomondo, Riccardo Di Sciacca, Domenico Di Raimondo, Gisella D'Aguanno, Serena Monaco, Eraldo Natalè, Sergio La Placa, Valentina Arnao, Luciana Marino, Rosaria Pecoraro, Antonio Pinto, Tuttolomondo, A, Di Sciacca, R, Di Raimondo, D, Serio, A, D’Aguanno, G, La Placa, S, Percoraro, R, Arnao, V, Marino, L, Monaco, S, Natalè, E, Licata, G, and Pinto, A more...
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Male ,medicine.medical_specialty ,stroke, TOAST subtype ,Immunology ,Inflammation ,Gastroenterology ,Brain Ischemia ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,In patient ,Acute ischemic stroke ,Stroke ,Aged ,Neurological deficit ,Aged, 80 and over ,business.industry ,Fibrinolysis ,Ischemic strokes ,Cerebral Infarction ,Plasma levels ,Middle Aged ,medicine.disease ,Neurology ,Physical therapy ,Female ,Neurology (clinical) ,Inflammation Mediators ,Intracranial Thrombosis ,medicine.symptom ,business ,Biomarkers - Abstract
BACKGROUND: The aim of our study was to evaluate in patients with acute ischemic stroke the relationship between immuno-inflammatory variables, clinical outcome and infarct site. MATERIALS AND METHODS: We evaluated plasma levels of IL-1beta, TNF-alpha, IL-6 and IL-10, E-selectin, P-selectin, sICAM-1 ,sVCAM-1 vWF, TPA and PAI-1. RESULTS: Patients with cardioembolic subtype showed significantly higher median plasma levels of TNF-alpha, IL-6, IL-1beta whereas the lacunar subtype showed significantly lower median plasma levels of TNF-alpha, IL-6 and IL-1beta. CONCLUSIONS: A significant association was noted between the severity of neurological deficit at admission, the diagnostic subtype and some inflammatory variables. more...
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- 2009
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48. Prognostic value of trans-thoracic echocardiography in patients with acute stroke and atrial fibrillation: findings from the RAF study
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Domenico Consoli, Alberto Chiti, Antonio Baldi, Massimo Del Sette, Alessandro Padovani, Cecilia Becattini, Kostantinos Vadikolias, Vera Volodina, Patrik Michel, Chrissoula Liantinioti, Davide Imberti, Naveed Akhtar, Cataldo D'Amore, Umberto Scoditti, Simona Sacco, Dirk Deleu, Michele Venti, Walter Ageno, Cindy Tiseo, Serena Monaco, Turgut Tatlisumak, Paolo Bovi, Valeria Caso, Francesca Guideri, Ulf Bodechtel, Luca Masotti, Faisal Ibrahim, Sebastiano D'Anna, Dorjan Zabzuni, Loris Poli, Azmil H. Abdul-Rahim, Kennedy R. Lees, Boris Doronin, Gino Gialdini, Lilla Szabó, Gayane Melikyan, Alberto Rigatelli, Kristian Barlinn, Giuseppe Martini, Alessio Pieroni, Tiziana Tassinari, Andrea Alberti, Nicola Falocci, Gianni Lorenzini, Jessica Kepplinger, Peter Vanacker, Maria Giulia Mosconi, Lars-Peder Pallesen, Christina Rueckert, Monica Acciarresi, Mario Maimone Baronello, Suzette Remillard, Danilo Toni, Rossana Tassi, Monica Carletti, Maurizio Paciaroni, Simona Marcheselli, Giancarlo Agnelli, László Csiba, Giorgio Bono, Jukka Putaala, Georgios Tsivgoulis, Johannes Gerber, Alessandro Pezzini, Francesco Corea, Giovanni Orlandi, Maria Cordier, Franco Galati, Antonio Carolei, Maria Luisa De Lodovici, Sung Il Sohn, and Licia Denti more...
- Subjects
Male ,medicine.medical_specialty ,Neurology ,Atrial enlargement ,030204 cardiovascular system & hematology ,Klinikai orvostudományok ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Risk Factors ,Internal medicine ,medicine ,Left atrial enlargement ,Secondary Prevention ,Humans ,Acute stroke ,cardiovascular diseases ,Stroke ,Neuroradiology ,Aged ,Acute stroke, Atrial fibrillation, Echocardiography, Outcome ,Outcome ,business.industry ,Atrial fibrillation ,Orvostudományok ,medicine.disease ,Prognosis ,Thrombosis ,Echocardiography ,Atrial Fibrillation ,Female ,Neurology (clinical) ,Cardiology ,Human medicine ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Anticoagulant therapy is recommended for the secondary prevention of stroke in patients with atrial fibrillation (AF). T he identification of patients at high risk for early recurrence, which are potential candidates to prompt anticoagulation, is crucial to justify the risk of bleeding associated with early anticoagulant treatment. The aim of this study was to evaluate in patients with acute ischemic stroke and AF the association between findings at trans-thoracic echocardiography (TTE) and 90 days recurrence. In consecutive patients with acute ischemic stroke and AF, TTE was performed within 7 days from hospital admission. Study outcomes were recurrent ischemic cerebrovascular events (stroke or TIA) and systemic embolism. 854 patients (mean age 76.3 +/- A 9.5 years) underwent a TTE evaluation; 63 patients (7.4 %) had at least a study outcome event. Left atrial thrombosis was present in 11 patients (1.3 %) among whom 1 had recurrent ischemic event. Left atrial enlargement was present in 548 patients (64.2 %) among whom 51 (9.3 %) had recurrent ischemic events. The recurrence rate in the 197 patients with severe left atrial enlargement was 11.7 %. On multivariate analysis, the presence of atrial enlargement (OR 2.13; 95 % CI 1.06-4.29, p = 0.033) and CHA(2)DS(2)-VASc score (OR 1.22; 95 % CI 1.04-1.45, p = 0.018, for each point increase) were correlated with ischemic recurrences. In patients with AF-associated acute stroke, left atrial enlargement is an independent marker of recurrent stroke and systemic embolism. The risk of recurrence is accounted for by severe atrial enlargement. TTE-detected left atrial thrombosis is relatively uncommon. more...
- Published
- 2016
49. Sex-related differences in risk factors, type of treatment received and outcomes in patients with atrial fibrillation and acute stroke: Results from the RAF-study (Early Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation)
- Author
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László Csiba, Francesca Guideri, Luca Masotti, Davide Imberti, Sokratis G. Papageorgiou, Dorjan Zabzuni, Giancarlo Agnelli, Loris Poli, Sebastiano D'Anna, Azmil H. Abdul-Rahim, Gino Gialdini, Umberto Scoditti, Giorgio Bono, Naveed Akhtar, Gianni Lorenzini, Alessandro Padovani, Dirk Deleu, Serena Monaco, Nicola Falocci, Cecilia Becattini, Jukka Putaala, Simona Sacco, Patrik Michel, Alberto Rigatelli, Kristian Barlinn, Maria Luisa De Lodovici, Gayane Melikyan, Ulf Bodechtel, Georgios Tsivgoulis, Boris Doronin, Cindy Tiseo, Monica Acciarresi, Alessandro Pezzini, Lilla Szabó, Rossana Tassi, Francesco Corea, Giovanni Orlandi, Maria Giulia Mosconi, Maria Cordier, Paolo Bovi, Licia Denti, Valeria Caso, Turgut Tatlisumak, Sung Il Sohn, Simona Marcheselli, Alessio Pieroni, Mario Maimone Baronello, Suzette Remillard, Maurizio Paciaroni, Danilo Toni, Cataldo D'Amore, Kateryna Antonenko, Monica Carletti, Antonio Baldi, Peter Vanacker, Christina Rueckert, Kennedy R. Lees, Michele Venti, Walter Ageno, Andrea Alberti, Lars-Peder Pallesen, Tiziana Tassinari, Johannes Gerber, Faisal Ibrahim, Domenico Consoli, Jessica Kepplinger, Kostantinos Vadikolias, Alberto Chiti, Massimo Del Sette, Vera Volodina, Franco Galati, Antonio Carolei, and Giuseppe Martini more...
- Subjects
medicine.medical_specialty ,anticoagulation therapy ,atrial fibrillation ,ischemic stroke ,secondary prevention ,Sex differences ,stroke outcome ,Early Recurrence ,Internal medicine ,Original Research Articles ,Medicine ,In patient ,cardiovascular diseases ,Risk factor ,Acute ischemic stroke ,Stroke ,Fibrillation ,business.industry ,Atrial fibrillation ,medicine.disease ,Cardiology ,Neurology (clinical) ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Cerebral Bleeding - Abstract
Introduction Atrial fibrillation is an independent risk factor of thromboembolism. Women with atrial fibrillation are at a higher overall risk for stroke compared to men with atrial fibrillation. The aim of this study was to evaluate for sex differences in patients with acute stroke and atrial fibrillation, regarding risk factors, treatments received and outcomes. Methods Data were analyzed from the “Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation” (RAF-study), a prospective, multicenter, international study including only patients with acute stroke and atrial fibrillation. Patients were followed up for 90 days. Disability was measured by the modified Rankin Scale (0–2 favorable outcome, 3–6 unfavorable outcome). Results Of the 1029 patients enrolled, 561 were women (54.5%) ( p Conclusions Women with atrial fibrillation were less likely to receive oral anticoagulants prior to and after stroke compared to men with atrial fibrillation, and when stroke occurred, regardless of the fact that in our study women were younger and with less severe stroke, outcomes did not differ between the sexes. more...
- Published
- 2016
50. Prestroke CHA
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Monica, Acciarresi, Maurizio, Paciaroni, Giancarlo, Agnelli, Nicola, Falocci, Valeria, Caso, Cecilia, Becattini, Simona, Marcheselli, Christina, Rueckert, Alessandro, Pezzini, Andrea, Morotti, Paolo, Costa, Alessandro, Padovani, Laszló, Csiba, Lilla, Szabó, Sung-Il, Sohn, Tiziana, Tassinari, Azmil H, Abdul-Rahim, Patrik, Michel, Maria, Cordier, Peter, Vanacker, Suzette, Remillard, Andrea, Alberti, Michele, Venti, Cataldo, D'Amore, Umberto, Scoditti, Licia, Denti, Giovanni, Orlandi, Alberto, Chiti, Gino, Gialdini, Paolo, Bovi, Monica, Carletti, Alberto, Rigatelli, Jukka, Putaala, Turgut, Tatlisumak, Luca, Masotti, Gianni, Lorenzini, Rossana, Tassi, Francesca, Guideri, Giuseppe, Martini, Georgios, Tsivgoulis, Kostantinos, Vadikolias, Chrissoula, Liantinioti, Francesco, Corea, Massimo, Del Sette, Walter, Ageno, Maria Luisa, De Lodovici, Giorgio, Bono, Antonio, Baldi, Sebastiano, D'Anna, Simona, Sacco, Antonio, Carolei, Cindy, Tiseo, Davide, Imberti, Dorjan, Zabzuni, Boris, Doronin, Vera, Volodina, Domenico, Consoli, Franco, Galati, Alessio, Pieroni, Danilo, Toni, Serena, Monaco, Mario Maimone, Baronello, Kristian, Barlinn, Lars-Peder, Pallesen, Jessica, Kepplinger, Ulf, Bodechtel, Johannes, Gerber, Dirk, Deleu, Gayane, Melikyan, Faisal, Ibrahim, Naveed, Akhtar, Maria Giulia, Mosconi, and Kennedy R, Lees more...
- Subjects
Male ,Asia ,Time Factors ,Risk Assessment ,Severity of Illness Index ,Decision Support Techniques ,Disability Evaluation ,Predictive Value of Tests ,Risk Factors ,Atrial Fibrillation ,Odds Ratio ,Humans ,Prospective Studies ,Aged ,Aged, 80 and over ,Chi-Square Distribution ,Prognosis ,Magnetic Resonance Imaging ,Europe ,Stroke ,Logistic Models ,ROC Curve ,Area Under Curve ,Multivariate Analysis ,Linear Models ,Female ,Tomography, X-Ray Computed - Abstract
The aim of this study was to investigate for a possible association between both prestroke CHAThis prospective study enrolled consecutive patients with acute ischemic stroke, AF, and assessment of prestroke CHAOf the 1020 patients included in the analysis, 606 patients had an admission NIHSS score lower and 414 patients higher than 10. At 90 days, 510 patients had mRS ≥3. A linear correlation was found between the prestroke CHAIn patients with AF, in addition to the risk of stroke, a high CHA more...
- Published
- 2015
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