24 results on '"Ilaria Martinelli"'
Search Results
2. Evoked and Event-Related Potentials as Biomarkers of Consciousness State and Recovery
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Ilaria Martinelli, Eléonore Bouchereau, Angela Marchi, Martine Gavaret, and Estelle Pruvost-Robieux
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Consciousness ,Mismatch negativity ,Physiology ,media_common.quotation_subject ,Disorders of consciousness ,Neuroimaging ,Event-related potential ,Physiology (medical) ,medicine ,Humans ,Unresponsive wakefulness syndrome ,Coma ,Child ,Evoked Potentials ,Minimally conscious state ,media_common ,Neural correlates of consciousness ,Invited Review ,Electroencephalography ,P3 ,Prognosis ,medicine.disease ,Functional imaging ,Neurology ,Consciousness Disorders ,Wakefulness ,Neurology (clinical) ,Auditory oddball ,Neuroscience ,Biomarkers - Abstract
Summary: The definition of consciousness has been the subject of great interest for many scientists and philosophers. To better understand how evoked potentials may be identified as biomarkers of consciousness and recovery, the different theoretical models sustaining neural correlates of consciousness are reviewed. A multimodal approach can help to better predict clinical outcome in patients presenting with disorders of consciousness. Evoked potentials are inexpensive and easy-to-implement bedside examination techniques. Evoked potentials are an integral part of prognostic evaluation, particularly in cases of cognitive motor dissociation. Prognostic criteria are well established in postanoxic disorders of consciousness, especially postcardiac arrest but are less well determined in other etiologies. In the early examination, bilateral absence of N20 in disorder of consciousness patients is strongly associated with unfavorable outcome (i.e., death or unresponsive wakefulness syndrome) especially in postanoxic etiologies. This predictive value is lower in other etiologies and probably also in children. Both N20 and mismatch negativity are proven outcome predictors for acute coma. Many studies have shown that mismatch negativity and P3a are characterized by a high prognostic value for awakening, but some patients presenting unresponsive wakefulness syndrome also process a P3a. The presence of long-latency event-related potential components in response to stimuli is indicative of a better recovery. All neurophysiological data must be integrated within a multimodal approach combining repeated clinical evaluation, neuroimaging, functional imaging, biology, and neurophysiology combining passive and active paradigms.
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- 2021
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3. Correction: hOA-DN30: a highly effective humanized single-arm MET antibody inducing remission of ‘MET-addicted’ cancers
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Ilaria Martinelli, Chiara Modica, Cristina Chiriaco, Cristina Basilico, James M. Hughes, Simona Corso, Silvia Giordano, Paolo M. Comoglio, and Elisa Vigna
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Cancer Research ,Oncology - Published
- 2022
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4. hOA-DN30: a highly effective humanized single-arm MET antibody inducing remission of ‘MET-addicted’ cancers
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Ilaria Martinelli, Chiara Modica, Cristina Chiriaco, Cristina Basilico, James M. Hughes, Simona Corso, Silvia Giordano, Paolo M. Comoglio, Elisa Vigna, Martinelli Ilaria, Modica Chiara, Chiriaco Cristina, Basilico Cristina, Hughes James, Corso Simona, Giordano Silvia, Comoglio Paolo Maria, Vigna Elisa, Martinelli, Ilaria, Modica, Chiara, Chiriaco, Cristina, Basilico, Cristina, Hughes, James M, Corso, Simona, Giordano, Silvia, Comoglio, Paolo M, and Vigna, Elisa
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Cancer Research ,Tumor ,Correction ,Proto-Oncogene Proteins c-met ,Cell Line ,Targeted therapy ,Mice ,Antibody ,Gastric cancer ,MET oncogene ,Animals ,Cell Line, Tumor ,Cell Proliferation ,Humans ,Signal Transduction ,Stomach Neoplasms ,Oncology - Abstract
Background The tyrosine kinase receptor encoded by the MET oncogene is a major player in cancer. When MET is responsible for the onset and progression of the transformed phenotype (MET-addicted cancers), an efficient block of its oncogenic activation results in potent tumor growth inhibition. Methods Here we describe a molecular engineered MET antibody (hOA-DN30) and validate its pharmacological activity in MET-addicted cancer models in vitro and in vivo. Pharmacokinetics and safety profile in non-human primates have also been assessed. Results hOA-DN30 efficiently impaired MET activation and the intracellular signalling cascade by dose and time dependent removal of the receptor from the cell surface (shedding). In vitro, the antibody suppressed cell growth by blocking cell proliferation and by concomitantly inducing cell death in multiple MET-addicted human tumor cell lines. In mice xenografts, hOA-DN30 induced an impressive reduction of tumor masses, with a wide therapeutic window. Moreover, the antibody showed high therapeutic efficacy against patient-derived xenografts generated from MET-addicted gastric tumors, leading to complete tumor regression and long-lasting effects after treatment discontinuation. Finally, hOA-DN30 showed a highly favorable pharmacokinetic profile and substantial tolerability in Cynomolgus monkeys. Conclusions hOA-DN30 unique ability to simultaneously erase cell surface MET and release the ‘decoy’ receptor extracellular region results in a paramount MET blocking action. Its remarkable efficacy in a large number of pre-clinical models, as well as its pharmacological features and safety profile in non-human primates, strongly envisage a successful clinical application of this novel single-arm MET therapeutic antibody for the therapy of MET-addicted cancers.
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- 2022
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5. Young Onset Alzheimer’s Disease Associated with C9ORF72 Hexanucleotide Expansion: Further Evidence for a Still Unsolved Association
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Giulia Vinceti, Chiara Gallingani, Elisabetta Zucchi, Ilaria Martinelli, Giulia Gianferrari, Cecilia Simonini, Roberta Bedin, Annalisa Chiari, Giovanna Zamboni, and Jessica Mandrioli
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Genetics ,Genetics (clinical) - Abstract
Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are recognized as part of a disease continuum (FTD-ALS spectrum), in which the most common genetic cause is chromosome 9 open reading frame 72 (C9ORF72) gene hexanucleotide repeat expansion. The clinical phenotype of patients carrying this expansion varies widely and includes diseases beyond the FTD-ALS spectrum. Although a few cases of patients with C9ORF72 expansion and a clinical or biomarker-supported diagnosis of Alzheimer’s disease (AD) have been described, they have been considered too sparse to establish a definite association between the C9ORF72 expansion and AD pathology. Here, we describe a C9ORF72 family with pleomorphic phenotypical expressions: a 54-year-old woman showing cognitive impairment and behavioral disturbances with both neuroimaging and cerebrospinal fluid (CSF) biomarkers consistent with AD pathology, her 49-year-old brother with typical FTD-ALS, and their 63-year-old mother with the behavioral variant of FTD and CSF biomarkers suggestive of AD pathology. The young onset of disease in all three family members and their different phenotypes and biomarker profiles make the simple co-occurrence of different diseases an extremely unlikely explanation. Our report adds to previous findings and may contribute to further expanding the spectrum of diseases associated with C9ORF72 expansion.
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- 2023
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6. Correction to: Italian version of the Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS): validation and longitudinal performance
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Andrea Fortuna, Daniele Sabbatini, Annachiara Frigo, Luca Bello, Francesca Calvi, Lorenzo Blasi, Giulia Gianferrari, Ilaria Martinelli, Giacomo Minicuci, Elena Pegoraro, Jessica Mandrioli, and Gianni Sorarù
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Neurology ,Neurology (clinical) - Published
- 2023
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7. Epidemiological, Clinical and Genetic Features of ALS in the Last Decade: A Prospective Population-Based Study in the Emilia Romagna Region of Italy
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Giulia, Gianferrari, Ilaria, Martinelli, Elisabetta, Zucchi, Cecilia, Simonini, Nicola, Fini, Marco, Vinceti, Salvatore, Ferro, Annalisa, Gessani, Elena, Canali, Franco, Valzania, Elisabetta, Sette, Maura, Pugliatti, Valeria, Tugnoli, Lucia, Zinno, Salvatore, Stano, Mario, Santangelo, Silvia, De Pasqua, Emilio, Terlizzi, Donata, Guidetti, Doriana, Medici, Fabrizio, Salvi, Rocco, Liguori, Veria, Vacchiano, Mario, Casmiro, Pietro, Querzani, Marco, Currò Dossi, Alberto, Patuelli, Simonetta, Morresi, Marco, Longoni, Patrizia, De Massis, Rita, Rinaldi, Annamaria, Borghi, Errals Group, Amedeo, Amedei, Jessica, Mandrioli, Gianferrari G., Martinelli I., Zucchi E., Simonini C., Fini N., Vinceti M., Ferro S., Gessani A., Canali E., Valzania F., Sette E., Pugliatti M., Tugnoli V., Zinno L., Stano S., Santangelo M., De Pasqua S., Terlizzi E., Guidetti D., Medici D., Salvi F., Liguori R., Vacchiano V., Casmiro M., Querzani P., Dossi M.C., Patuelli A., Morresi S., Longoni M., De Massis P., Rinaldi R., Borghi A., Amedei A., and Mandrioli J.
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amyotrophic lateral sclerosis ,clinical features ,epidemiology ,genetics ,incidence ,population-based registry ,Medicine (miscellaneous) ,amyotrophic lateral sclerosi ,genetic ,General Biochemistry, Genetics and Molecular Biology ,clinical feature - Abstract
Increased incidence rates of amyotrophic lateral sclerosis (ALS) have been recently reported across various Western countries, although geographic and temporal variations in terms of incidence, clinical features and genetics are not fully elucidated. This study aimed to describe demographic, clinical feature and genotype–phenotype correlations of ALS cases over the last decade in the Emilia Romagna Region (ERR). From 2009 to 2019, our prospective population-based registry of ALS in the ERR of Northern Italy recorded 1613 patients receiving a diagnosis of ALS. The age- and sex-adjusted incidence rate was 3.13/100,000 population (M/F ratio: 1.21). The mean age at onset was 67.01 years; women, bulbar and respiratory phenotypes were associated with an older age, while C9orf72-mutated patients were generally younger. After peaking at 70–75 years, incidence rates, among women only, showed a bimodal distribution with a second slight increase after reaching 90 years of age. Familial cases comprised 12%, of which one quarter could be attributed to an ALS-related mutation. More than 70% of C9orf72-expanded patients had a family history of ALS/fronto-temporal dementia (FTD); 22.58% of patients with FTD at diagnosis had C9orf72 expansion (OR 6.34, p = 0.004). In addition to a high ALS incidence suggesting exhaustiveness of case ascertainment, this study highlights interesting phenotype–genotype correlations in the ALS population of ERR.
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- 2022
8. Premorbid personality in frontotemporal dementia: Amyotrophic lateral sclerosis spectrum
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Giulia Vinceti, Chiara Gallingani, Luigi Fiondella, Chiara Carbone, Simone Salemme, Manuela Tondelli, Ilaria Martinelli, Elisabetta Zucchi, Jessica Mandrioli, Annalisa Chiari, and Giovanna Zamboni
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2021
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9. The landscape of cognitive impairment in superoxide dismutase 1-amyotrophic lateral sclerosis
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Ilaria Martinelli, Elisabetta Zucchi, Cecilia Simonini, Giulia Gianferrari, Giovanna Zamboni, Marcello Pinti, and Jessica Mandrioli
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Developmental Neuroscience - Abstract
Although mutations in the superoxide dismutase 1 gene account for only a minority of total amyotrophic lateral sclerosis cases, the discovery of this gene has been crucial for amyotrophic lateral sclerosis research. Since the identification of superoxide dismutase 1 in 1993, the field of amyotrophic lateral sclerosis genetics has considerably widened, improving our understanding of the diverse pathogenic basis of amyotrophic lateral sclerosis. In this review, we focus on cognitive impairment in superoxide dismutase 1-amyotrophic lateral sclerosis patients. Literature has mostly reported that cognition remains intact in superoxide dismutase 1-amyotrophic lateral sclerosis patients, but recent reports highlight frontal lobe function frailty in patients carrying different superoxide dismutase 1-amyotrophic lateral sclerosis mutations. We thoroughly reviewed all the various mutations reported in the literature to contribute to a comprehensive database of superoxide dismutase 1-amyotrophic lateral sclerosis genotype-phenotype correlation. Such a resource could ultimately improve our mechanistic understanding of amyotrophic lateral sclerosis, enabling a more robust assessment of how the amyotrophic lateral sclerosis phenotype responds to different variants across genes, which is important for the therapeutic strategy targeting genetic mutations. Cognition in superoxide dismutase 1-amyotrophic lateral sclerosis deserves further longitudinal research since this peculiar frailty in patients with similar mutations can be conditioned by external factors, including environment and other unidentified agents including modifier genes.
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- 2023
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10. Identification and prediction of ALS subgroups using machine learning
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Bryan J. Traynor, Ilaria Martinelli, Roy H. Campbell, Adriano Chiò, Anant Dadu, Rosario Vasta, Brunn F, Elisabetta Zucchi, Antonio Canosa, Faraz Faghri, Cristina Moglia, Letizia Mazzini, Mike A. Nalls, Jessica Mandrioli, and Andrea Calvo
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education.field_of_study ,business.industry ,Clinical study design ,Population ,Supervised learning ,Context (language use) ,Machine learning ,computer.software_genre ,medicine.disease ,Ensemble learning ,Clinical trial ,medicine ,Clinical significance ,Artificial intelligence ,Amyotrophic lateral sclerosis ,education ,business ,computer - Abstract
SUMMARYBackgroundThe disease entity known as amyotrophic lateral sclerosis (ALS) is now known to represent a collection of overlapping syndromes. A better understanding of this heterogeneity and the ability to distinguish ALS subtypes would improve the clinical care of patients and enhance our understanding of the disease. Subtype profiles could be incorporated into the clinical trial design to improve our ability to detect a therapeutic effect. A variety of classification systems have been proposed over the years based on empirical observations, but it is unclear to what extent they genuinely reflect ALS population substructure.MethodsWe applied machine learning algorithms to a prospective, population-based cohort consisting of 2,858 Italian patients diagnosed with ALS for whom detailed clinical phenotype data were available. We replicated our findings in an independent population-based cohort of 1,097 Italian ALS patients.FindingsWe found that semi-supervised machine learning based on UMAP applied to the output of a multi-layered perceptron neural network produced the optimum clustering of the ALS patients in the discovery cohort. These clusters roughly corresponded to the six clinical subtypes defined by the Chiò classification system (bulbar ALS, respiratory ALS, flail arm ALS, classical ALS, pyramidal ALS, and flail leg ALS). The same clusters were identified in the replication cohort. A supervised learning approach based on ensemble learning identified twelve clinical parameters that predicted ALS clinical subtype with high accuracy (area under the curve = 0·94).InterpretationOur data-driven study provides insight into the ALS population’s substructure and demonstrates that the Chiò classification system robustly identifies ALS subtypes. We provide an interactive website (https://share.streamlit.io/anant-dadu/machinelearningforals/main) so that clinical researchers can predict the clinical subtype of an ALS patient based on a small number of clinical parameters.FundingNational Institute on Aging and the Italian Ministry of Health.RESEARCH IN CONTEXTEvidence before this studyWe searched PubMed for articles published in English from database inception until January 5, 2021, about the use of machine learning and the identification of clinical subtypes within the amyotrophic lateral sclerosis (ALS) population, using the search terms “machine learning”, AND “classification”, AND “amyotrophic lateral sclerosis”. This inquiry identified twenty-nine studies. Most previous studies used machine learning to diagnose ALS (based on gait, imaging, electromyography, gene expression, proteomic, and metabolomic data) or improve brain-computer interfaces. One study used machine learning algorithms to stratify ALS postmortem cortex samples into molecular subtypes based on transcriptome data. Kueffner and colleagues crowdsourced the development of machine learning algorithms to approximately thirty teams to obtain a consensus in an attempt to identify ALS patients subpopulation. In addition to clinical trial information in the PRO-ACT database (www.ALSdatabase.org), this effort used data from the Piedmont and Valle d’Aosta Registry for ALS (PARALS). Four ALS patient categories were identified: slow progressing, fast progressing, early stage, and late stage. This approach’s clinical relevance was unclear, as all ALS patients will necessarily pass through an early and late stage of the disease.Furthermore, no attempt was made to discern which of the existing clinical classification systems, such as the El Escorial criteria, the Chiò classification system, and the King’s clinical staging system, can identify ALS subtypes. We concluded that there remained an unmet need to identify the ALS population’s substructure in a data-driven, non-empirical manner. Building on this, there was a need for a tool that reliably predicts the clinical subtype of an ALS patient. This knowledge would improve our understanding of the clinical heterogeneity associated with this fatal neurodegenerative disease.Added value of this studyThis study developed a machine learning algorithm to detect ALS patients’ clinical subtypes using clinical data collected from the 2,858 Italian ALS patients in PARALS. Ascertainment of these patients within the catchment area was near complete, meaning that the dataset truly represented the ALS population. We replicated our approach using clinical data obtained from an independent cohort of 1,097 Italian ALS patients that had also been collected in a population-based, longitudinal manner. Semi-supervised learning based on Uniform Manifold Approximation and Projection (UMAP) applied to a multilayer perceptron neural network provided the optimum results based on visual inspection. The observed clusters equated to the six clinical subtypes previously defined by the Chiò classification system (bulbar ALS, respiratory ALS, flail arm ALS, classical ALS, pyramidal ALS, and flail leg ALS). Using a small number of clinical parameters, an ensemble learning approach could predict the ALS clinical subtype with high accuracy (area under the curve = 0·94).Implications of all available evidenceAdditional validation is required to determine these algorithms’ accuracy and clinical utility in assigning clinical subtypes. Nevertheless, our algorithms offer a broad insight into the clinical heterogeneity of ALS and help to determine the actual subtypes of disease that exist within this fatal neurodegenerative syndrome. The systematic identification of ALS subtypes will improve clinical care and clinical trial design.
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- 2021
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11. The Impact of Lifetime Alcohol and Cigarette Smoking Loads on Amyotrophic Lateral Sclerosis Progression: A Cross-Sectional Study
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Sergio Russo, Dafin F. Muresanu, Massimiliano Copetti, Vitalie Lisnic, Letizia Mazzini, Maurizio Leone, Andrea Fontana, Andrei Ivashynka, Valentina Renna, Michele Zarrelli, Aliona Cucovici, Ilaria Martinelli, Ileana Gagliardi, and Jessica Mandrioli
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0301 basic medicine ,medicine.medical_specialty ,amyotrophic lateral sclerosis ,Cross-sectional study ,Science ,Alcohol drinking ,Amyotrophic lateral sclerosis ,Disease progression rate ,Prognosis ,Questionnaire ,Smoking ,Alcohol ,Disease ,Article ,General Biochemistry, Genetics and Molecular Biology ,smoking ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cigarette smoking ,Internal medicine ,Medicine ,Ecology, Evolution, Behavior and Systematics ,business.industry ,questionnaire ,Disease progression ,Paleontology ,Former Smoker ,medicine.disease ,alcohol drinking ,030104 developmental biology ,disease progression rate ,nervous system ,chemistry ,Multicenter study ,Space and Planetary Science ,prognosis ,business ,030217 neurology & neurosurgery - Abstract
Background—Amyotrophic lateral sclerosis (ALS) is a devastating and untreatable motor neuron disease, smoking and alcohol drinking may impact its progression rate. Objective—To ascertain the influence of smoking and alcohol consumption on ALS progression rates. Methods—Cross-sectional multicenter study, including 241 consecutive patients (145 males), mean age at onset was 59.9 ± 11.8 years. Cigarette smoking and alcohol consumption data were collected at recruitment through a validated questionnaire. Patients were categorized into three groups according to ΔFS (derived from the ALS Functional Rating Scale-Revised and disease duration from onset): slow (n = 81), intermediate (80), and fast progressors (80). Results—Current smokers accounted for 44 (18.3%) of the participants, former smokers accounted for 10 (4.1%), and non-smokers accounted for 187 (77.6%). The age of ALS onset was lower in current smokers than non-smokers, and the ΔFS was slightly, although not significantly, higher for smokers of >, 14 cigarettes/day. Current alcohol drinkers accounted for 147 (61.0%) of the participants, former drinkers accounted for 5 (2.1%), and non-drinkers accounted for 89 (36.9%). The log(ΔFS) was weakly correlated only with the duration of alcohol consumption (p = 0.028), but not with the mean number of drinks/day or the drink-years. Conclusions: This cross-sectional multicenter study suggested a possible minor role for smoking in worsening disease progression. A possible interaction with alcohol drinking was suggested.
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- 2021
12. A novel p.N66T mutation in exon 3 of the SOD1 gene: report of two families of ALS patients with early cognitive impairment
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Valentina Pecoraro, Tommaso Trenti, Ilaria Martinelli, Elisabetta Zucchi, Annalisa Gessani, Adriano Chiò, Nicola Fini, and Jessica Mandrioli
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Male ,ALS genetics ,animal diseases ,SOD1 ,Neuropsychological Tests ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Superoxide Dismutase-1 ,medicine ,Humans ,Cognitive Dysfunction ,Amyotrophic lateral sclerosis ,Cognitive impairment ,Gene ,cognitive impairment ,Aged ,Genetics ,business.industry ,Amyotrophic Lateral Sclerosis ,nutritional and metabolic diseases ,Middle Aged ,medicine.disease ,ALS FTD ,nervous system diseases ,Pedigree ,Neurology ,Mutation (genetic algorithm) ,Mutation ,Neurology (clinical) ,ALS phenotype ,business ,familial ALS ,030217 neurology & neurosurgery - Abstract
Introduction: To date more than 180 different mutations in the SOD1 gene have been described in ALS; some of these mutations are associated to peculiar clinical features and have contributed to the...
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- 2020
13. The Innovation of the Cashierless Store: A Preliminary Analysis in Italy
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Patrizia Gazzola, Daniele Grechi, Ilaria Martinelli, and Roberta Pezzetti
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Renewable Energy, Sustainability and the Environment ,technology ,Geography, Planning and Development ,cashierless ,consumer behaviour ,smart payment ,survey ,Management, Monitoring, Policy and Law - Abstract
The retail sector, under the pressure of digitalization and technological innovation, has experienced profound changes in the last decade, and retailers have had to cope with these changes by implementing new business models and competitive strategies with the aim of satisfying the consumers’ needs. In the last few decades, the sector has been affected by different new trends, from the birth of supermarkets to the advent of e-commerce, up to the introduction of cashierless stores. The latter represents a new category of store that is totally computer-based and digitalized, in which the use of cameras, sensors and self-shelves minimizes human interaction. Amazon pioneered this emerging concept, with the launch of Amazon Go, but other start-up companies are rapidly entering the cashierless retail market and embracing the challenge. The purpose of this paper is to analyze the knowledge of Italian consumers of cashierless shops, and the relevance of different factors related to this new kind of shops. A questionnaire was sent to a sample of more than 1000 consumers to identify and evaluate the actual situation and knowledge of this phenomenon, which is not yet diffuse in Italy. A statistical analysis, regarding both their knowledge about cashierless stores and the customer experience, is provided to discuss the most relevant factors affecting the customers’ perceptions and attitudes, with a comparison per gender and type of users. The results of the provided analysis reveal that the phenomenon is very little known, and this is certainly influenced by the lack of these stores in Italy.
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- 2022
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14. Insights into the genetic epidemiology of spinal and bulbar muscular atrophy: prevalence estimation and multiple founder haplotypes in the Veneto Italian region
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Ilaria Martinelli, Giorgia Querin, Gianni Sorarù, Cinzia Bertolin, Elena Pegoraro, and Maria Pennuto
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Male ,medicine.medical_specialty ,Single-nucleotide polymorphism ,Bulbo-Spinal Atrophy, X-Linked ,03 medical and health sciences ,0302 clinical medicine ,Epidemiology ,Humans ,Medicine ,Registries ,030212 general & internal medicine ,Genotyping ,Aged ,Genetics ,business.industry ,Haplotype ,Middle Aged ,medicine.disease ,Founder Effect ,Spinal and bulbar muscular atrophy ,Haplotypes ,Italy ,Neurology ,Genetic epidemiology ,Genetic marker ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Founder effect - Abstract
BACKGROUND AND PURPOSE Literature data on spinal and bulbar muscular atrophy (SBMA) epidemiology are limited and restricted to specific populations. The aim of our study was to accurately collect information about SBMA patients living in the Veneto region in Italy to compute reliable epidemiological data. Androgen receptor (AR) lineages were genotyped to evaluate the presence of a founder effect. METHODS A prevalence survey considering all SBMA patients diagnosed in the Italian Veneto region on 31 January 2018 was carried out. The presence of different haplotypes obtained genotyping 15 polymorphic markers (single nucleotide polymorphisms and short tandem repeats) around the AR gene was evaluated. RESULTS Based on 68 patients, the punctual prevalence of the disease on 31 January 2018 was 2.58/100 000 (95% confidence interval 1.65-3.35) in the male population. Five different haplotypes were identified, confirming the existence of multiple founder effects. It was also observed that, within the same haplotype, patients had a similar CAG repeat number (P-value
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- 2018
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15. Premorbid personality in the frontotemporal dementia - amyotrophic lateral sclerosis spectrum
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Chiara Carbone, Giulia Vinceti, Manuela Tondelli, Elisabetta Zucchi, Chiara Gallingani, Giovanna Zamboni, Luigi Fiondella, Ilaria Martinelli, Simone Salemme, Jessica Mandrioli, and Annalisa Chiari
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medicine.medical_specialty ,Neurology ,business.industry ,media_common.quotation_subject ,Medicine ,Personality ,Neurology (clinical) ,Audiology ,Amyotrophic lateral sclerosis ,business ,medicine.disease ,Frontotemporal dementia ,media_common - Published
- 2021
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16. Serum CHI3L1 in amyotrophic lateral sclerosis: A useful tool for prognostic definition?
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Serena Carra, Jessica Mandrioli, Elisabetta Zucchi, Ilaria Martinelli, Cecilia Simonini, Roberta Bedin, and Giulia Gianferrari
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Pathology ,medicine.medical_specialty ,Neurology ,business.industry ,Medicine ,Neurology (clinical) ,Amyotrophic lateral sclerosis ,business ,medicine.disease ,CHI3L1 - Published
- 2021
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17. A sight into the elderly ALS patients in Emilia Romagna region: Epidemiological and clinical features of late onset ALS in a prospective population-based study
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Silvia Depasqua, Elisabetta Canali, Fabrizio Salvi, Lucia Zinno, Jessica Mandrioli, Cecilia Simonini, Simonetta Morresi, Doriana Medici, Marco Vinceti, Marco Curròdossi, Elisabetta Zucchi, Giulia Gianferrari, Maura Pugliatti, Rocco Liguori, Ilaria Martinelli, Mario Santangelo, Alberto Patuelli, Nicola Fini, Emilio Terlizzi, Veria Vacchiano, Elisabetta Sette, and M. Casmiro
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Population based study ,Pediatrics ,medicine.medical_specialty ,Neurology ,business.industry ,Epidemiology ,medicine ,Late onset ,Neurology (clinical) ,business - Published
- 2021
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18. Brain MRI shows white matter sparing in Kennedy's disease and slow-progressing lower motor neuron disease
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Federica Agosta, Giorgia Querin, Christian Lunetta, Pilar M. Ferraro, Massimo Filippi, Edoardo G. Spinelli, Nilo Riva, Gianni Sorarù, Cinzia Bertolin, Andrea Fontana, Ilaria Martinelli, Spinelli, E. G., Agosta, F., Ferraro, P. M., Querin, G., Riva, N., Bertolin, C., Martinelli, I., Lunetta, C., Fontana, A., Soraru, G., and Filippi, M.
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Adult ,Male ,Pathology ,medicine.medical_specialty ,corticospinal tract ,Central nervous system ,Bulbo-Spinal Atrophy, X-Linked ,Corpus callosum ,050105 experimental psychology ,White matter ,03 medical and health sciences ,0302 clinical medicine ,Fractional anisotropy ,medicine ,Humans ,0501 psychology and cognitive sciences ,Radiology, Nuclear Medicine and imaging ,amyotrophic lateral sclerosi ,Amyotrophic lateral sclerosis ,Motor Neuron Disease ,Research Articles ,Aged ,Radiological and Ultrasound Technology ,business.industry ,05 social sciences ,diffusion tensor MRI ,Amyotrophic Lateral Sclerosis ,Brain ,Kennedy's disease ,Motor neuron ,Middle Aged ,medicine.disease ,White Matter ,lower motor neuron disease ,medicine.anatomical_structure ,Diffusion Tensor Imaging ,Neurology ,Corticospinal tract ,Female ,Neurology (clinical) ,Anatomy ,business ,030217 neurology & neurosurgery ,Tractography - Abstract
The extent of central nervous system involvement in Kennedy's disease (KD) relative to other motor neuron disease (MND) phenotypes still needs to be clarified. In this study, we investigated cortical and white matter (WM) MRI alterations in 25 patients with KD, compared with 24 healthy subjects, 25 patients with sporadic amyotrophic lateral sclerosis (ALS), and 35 cases with lower motor neuron-predominant disease (LMND). LMND patients were clinically differentiated into 24 fast and 11 slow progressors. Whole-brain cortical thickness, WM tract-based spatial statistics and corticospinal tract (CST) tractography analyses were performed. No significant difference in terms of cortical thickness was found between groups. ALS patients showed widespread decreased fractional anisotropy and increased mean (MD) and radial diffusivity (radD) in the CST, corpus callosum and fronto-temporal extra-motor tracts, compared with healthy controls and other patient groups. CST tractography showed significant alterations of DT MRI metrics in ALS and LMND-fast patients whereas KD and LMND-slow patients were comparable with healthy controls. Our study demonstrated the absence of WM abnormalities in patients with KD and LMND-slow, in contrast with diffuse WM damage in ALS and focal CST degeneration in LMND-fast, supporting the use of DT MRI measures as powerful tools to differentiate fast- and slow-progressing MND syndromes, including KD.
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- 2019
19. Validation of the Italian version of the SBMA Functional Rating Scale as outcome measure
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Elena Pegoraro, Caterina Mariotti, Davide Pareyson, Giorgia Querin, Luca Bello, Gianni Sorarù, Elisa DaRe, Ilaria Martinelli, and Cinzia Bertolin
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Adult ,0301 basic medicine ,medicine.medical_specialty ,Psychometrics ,Functional scale ,Scale (ratio) ,Varimax rotation ,Dermatology ,Severity of Illness Index ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Cronbach's alpha ,Italian version ,SBMA ,Rating scale ,Validation ,medicine ,Humans ,Respiratory function ,Biomarkers ,2708 ,Neurology (clinical) ,Psychiatry and Mental Health ,Aged ,Reproducibility of Results ,General Medicine ,Middle Aged ,medicine.disease ,Muscular Disorders, Atrophic ,Psychiatry and Mental health ,Spinal and bulbar muscular atrophy ,030104 developmental biology ,Italy ,Convergent validity ,Exercise Test ,Physical therapy ,Psychology ,030217 neurology & neurosurgery - Abstract
The Spinal and Bulbar Muscular Atrophy Functional Rating Scale (SBMAFRS) is an established rating instrument used to assess the functional status of patients with Spinal and Bulbar Muscular Atrophy (SBMA). Our aim was to validate an Italian version of the scale. We administered the SBMAFRS to sixty SBMA patients during routine follow-up of clinical evaluations. To estimate the test stability, the scale was re-administered to a subset of 39 randomly selected patients after 8 weeks. The patients underwent clinical evaluation including 6-min walk. Psychometric analysis included reliability assessment and factorial analysis. To evaluate convergent validity, correlations between SBMAFRS items and muscular force assessed by manual testing, ALSFRS total score and subscales scores, and forced vital capacity, were performed. Internal consistency as measured by Cronbach's alpha (total scale 0.85) was high. Test-retest reliability assessed by Spearman's rho was also high. Principal component analysis with varimax rotation yielded a four-factor solution accounting for approximately 79 % of the variance. The scale total score and subscales score were strongly correlated with respective items and subscores of the ALSFRS, with respiratory function and with the 6-min walk test. In conclusion, we performed an Italian validation of the only existing disease-specific Functional Rating Scale for SBMA patients. This scale will be a useful tool not only in the clinical practice but also as an outcome measure in upcoming clinical trials.
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- 2016
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20. Safety, tolerability, and preliminary efficacy of an IGF-1 mimetic in patients with spinal and bulbar muscular atrophy: a randomised, placebo-controlled trial
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Christopher Grunseich, Ram Miller, Therese Swan, David J Glass, Mohamed El Mouelhi, Mara Fornaro, Olivier Petricoul, Igor Vostiar, Ronenn Roubenoff, Matthew N Meriggioli, Angela Kokkinis, Robert D Guber, Maher S Budron, John Vissing, Gianni Soraru, Tahseen Mozaffar, Albert Ludolph, John T Kissel, Kenneth H Fischbeck, Julia Dahlqvist, Nanna Witting, Ilaria Martinelli, Giorgia Querin, Namita A Goyal, Tiyonnoh M Cash, Brian Minton, Angela Rosenbohm, Ulrike Weiland, Patrick Weydt, Sharon Chelnick, Stanley Iyadurai, and Wendy King
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0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Neuromuscular disease ,International Cooperation ,Placebo-controlled study ,Bulbo-Spinal Atrophy, X-Linked ,Placebo ,law.invention ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Double-Blind Method ,law ,Biomimetics ,Internal medicine ,Medicine ,Humans ,Insulin-Like Growth Factor I ,Myopathy ,Adverse effect ,Aged ,Dose-Response Relationship, Drug ,business.industry ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Spinal and bulbar muscular atrophy ,Muscular Atrophy ,030104 developmental biology ,Treatment Outcome ,Tolerability ,Female ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Summary Background Spinal and bulbar muscular atrophy is an X-linked neuromuscular disease caused by CAG repeat expansion in the androgen receptor gene. Patients with this disease have low concentrations of insulin-like growth factor-1 (IGF-1), and studies of overexpression and administration of IGF-1 showed benefit in a transgenic model; thus the IGF-1 pathway presents as a potential treatment target. We assessed safety, tolerability, and preliminary efficacy of BVS857, an IGF-1 mimetic, in patients with spinal and bulbar muscular atrophy. Methods In this randomised, double-blind, placebo-controlled trial, we recruited patients from neuromuscular centres in Denmark (Copenhagen), Germany (Ulm), Italy (Padova), and three sites within the USA (Bethesda, MD; Irvine, CA; and Columbus, OH). Eligible patients were 18 years or older with a confirmed genetic diagnosis of spinal and bulbar muscular atrophy, were ambulatory, had symptomatic weakness, and had serum IGF-1 concentrations of 170 ng/mL or lower. Patients were randomly assigned (2:1) to study drug or placebo by a number scheme. Patients, investigators, and study personnel were masked to treatment assignment. After a safety and tolerability assessment with eight patients, BVS857 was administered once a week (0·06 mg/kg intravenously) for 12 weeks. Primary outcome measures were safety, tolerability, and the effects of BVS857 on thigh muscle volume (TMV) measured by MRI. The ratio of TMV at day 85 to baseline was analysed with ANCOVA per protocol. Secondary outcomes of muscle strength and function were measured with the Adult Myopathy Assessment Tool, lean body mass through dual energy x-ray absorptiometry, and BVS857 pharmacokinetics. This trial was registered with ClinicalTrials.gov , NCT02024932 . Findings 31 patients were assessed for eligibility, 27 of whom were randomly assigned to either BVS857 treatment (n=18) or placebo (n=9), and 24 were included in the preliminary efficacy analysis (BVS857 group, n=15; placebo group, n=9). BVS857 was generally safe with no serious adverse events. No significant differences were found in adverse events between the BVS857 and placebo groups. Immunogenicity was detected in 13 (72%) of 18 patients in the BVS857 group, including crossreacting antibodies with neutralising capacity to endogenous IGF-1 in five patients. TMV decreased from baseline to day 85 in the placebo group (–3·4% [–110 cm3]) but not in the BVS857 group (0% [2 cm3]). A significant difference in change in TMV was observed in the BVS857 group versus the placebo group (geometric-mean ratio 1·04 [90% CI 1·01–1·07]; p=0·02). There were no differences between groups in measures of muscle strength and function. Interpretation TMV remained stable in patients with spinal and bulbar muscular atrophy after being given BVS857 for 12 weeks. The intervention was associated with high incidence of immunogenicity and did not improve muscle strength or function. Additional studies might be needed to assess the efficacy of activating the IGF-1 pathway in this disease. Funding Novartis Pharmaceuticals and the US National Institutes of Health.
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- 2018
21. P14-S Latency of Mismatch Negativity as a predictor of outcome in critically patients with subarachnoid haemorrhage
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Giulia Naim, Ilaria Martinelli, Celine Ramdani, Estelle Pruvost, Tarek Sharshar, Angela Marchi, and Martine Gavaret
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Coma ,medicine.medical_specialty ,N100 ,medicine.diagnostic_test ,business.industry ,Sedation ,Mismatch negativity ,Physical examination ,Audiology ,Electroencephalography ,medicine.disease ,Sensory Systems ,Neurology ,Physiology (medical) ,medicine ,Neurology (clinical) ,medicine.symptom ,business ,Neurophysiological Monitoring ,Persistent vegetative state - Abstract
Background Multimodal neurophysiological markers support clinical assessments in individuals with disorders of consciousness (DoC). Few studies focused on subarachnoid haemorrhage (SAH) related coma. Furthermore, these patients often need sedation during the acute phase, making behavioral and neurophysiological monitoring challenging. We investigated which neurophysiological marker could better predict outcome in acute DoC related to SAH. Methods We studied 14 SAH patients admitted in the Sainte Anne hospital neurological ICU, between Oct 2017 and June 2018. All patients underwent within the first 72 h: clinical evaluation, EEG and multimodal evoked potentials (somatosensory potentials, brainstem auditory evoked potentials (BAEPs), late latency event-related potentials, N100 and mismatch negativity (MMN)). Quantitative EEG analysis using spectral and connectivity analysis was performed. According to the Glascow Outcome scale (GOS), we defined two clinical outcome groups: favorable (F) and unfavorable (UF). Results Clinical examination, EEG visual and quantitative analysis, presence of N20, BAEP, N100 and MMN were not significantly different in the two groups. However, mean latencies of N100 (F = 80 ms; UF = 106 ms;) and of MMN (F = 139 ms; UF = 197msec) were significantly different in the two groups (Mann Whitney test, respectively p = 0.017 and p = 0.035). Conclusions This study suggests that during the acute phase, in sedated patients with DoC related to SAH, latencies of N100 and latencies of MMN could be more discriminatory than the “classical” interpretation of these markers (present/absent) and the EEG analysis, in term of prognosis. These results need to be confirmed in a larger study.
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- 2019
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22. Glubran2 Surgical Glue: In Vitro Evaluation of Adhesive and Mechanical Properties
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Silvia Kull, Ilaria Martinelli, Sara Tonlorenzi, Enrica Briganti, Paola Losi, Giorgio Soldani, and Dario Spiller
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medicine.medical_specialty ,Materials science ,Polymers ,Swine ,Fibrin Tissue Adhesive ,macromolecular substances ,In Vitro Techniques ,Fibrin ,law.invention ,Surgical glue ,law ,Adhesives ,Tensile Strength ,Materials Testing ,Ultimate tensile strength ,otorhinolaryngologic diseases ,medicine ,Animals ,Cyanoacrylates ,Composite material ,Fibrin glue ,GLUE ,Skin ,chemistry.chemical_classification ,biology ,technology, industry, and agriculture ,Polymer ,Elasticity ,Surgery ,chemistry ,Cyanoacrylate ,biology.protein ,Stress, Mechanical ,Adhesive - Abstract
Background In surgical and endoscopic procedures, tissue adhesives are commonly used as reinforcement of sutures or as bonding and hemostatic agents. Fibrin glues do not guarantee adequate properties for many clinical applications; on the contrary, cyanoacrylate glues guarantee high bonding strength between biologic tissues. The aim of this study was to provide evidence regarding adhesive and strength properties of a widely used cyanoacrylate glue, Glubran2, GEM s.r.l., Viareggio, Italy. Comparative tests were also carried out on a commercial fibrin glue. Material and methods Glubran2 is a modified n-butyl-2-cyanoacrylate glue approved for internal and external use, in Europe. The glue, on contact with living tissues polymerizes rapidly, generating a film that guarantees firm adherence of tissues. In this study, adhesive properties on biologic substrates, both of Glubran2 and of fibrin glue, were investigated according to American Society for Testing and Materials (ASTM) standards, while their strength, after polymerization on an inert substrate, was investigated according to Deutsches Institut Fur Normung (DIN) standards. Results All tests evidenced a strong bonding capability of Glubran2 on biologic tissues and high tensile strength of polymerized film; high breaking strength of polymerized glue was highlighted by tensile tests. Conclusion The present study fills the gap concerning Glubran2 adhesive and tensile properties. All tests showed the intrinsic tensile strength of polymerized Glubran2 and its capability to realize a higher-resistance bonding among biologic tissues, in comparison with fibrin glue, giving strong indication of its usefulness in surgical and endoscopic practice, especially in a wet environment.
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- 2009
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23. Evaluation of a new composite prosthesis for the repair of abdominal wall defects
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Paola Losi, Ilaria Martinelli, Enrica Briganti, Giorgio Soldani, Dario Spiller, Marco Scoccianti, and Antonella Munaò
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Male ,Materials science ,Polymers ,medicine.medical_treatment ,Composite number ,Polyurethanes ,Biomedical Engineering ,Biophysics ,Silicones ,Adhesion (medicine) ,Bioengineering ,Tissue Adhesions ,Prosthesis ,Biomaterials ,Abdominal wall ,Prosthesis Implantation ,medicine ,Animals ,Regeneration ,Dimethylpolysiloxanes ,Composite material ,Abdominal wall defect ,Abdominal Wall ,Intestinal loops ,Prostheses and Implants ,Surgical Mesh ,medicine.disease ,Hernia, Abdominal ,medicine.anatomical_structure ,Microscopy, Electron, Scanning ,Wettability ,Implant ,Rabbits ,Visceral peritoneum ,Hydrophobic and Hydrophilic Interactions ,Biomedical engineering - Abstract
The degree of integration of biomaterials used in the repair of abdominal wall defects seems to depend upon the structure of the prosthesis. The present investigation evaluates the behaviour in terms of adhesion formation and integration of a new composite prosthesis that could be employed in this clinical application. Full-thickness abdominal wall defects (7 × 5 cm) were created in 16 anaesthetized New Zealand white rabbits and the prosthesis were placed in direct contact with the visceral peritoneum during the experiment. The defects were repaired with a composite prosthesis or pure polypropylene mesh to establish two study groups (n = 8 each). The composite device was constituted by a polypropylene mesh physically attached to a poly(ether)urethane–polydimethylsiloxane laminar sheet. Animals were sacrificed 7, 14, 21 and 30 days after implant and prosthesis/surrounding tissue specimens subjected to light and electron microscopy. Firm adhesions were detected in the polypropylene implants, while they were not present in the composite implants. The excellent behaviour of the composite prosthesis shown in this study warrants further investigation on its use for the repair of abdominal wall defects when a prosthetic device needs to be placed in contact with the intestinal loops.
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- 2006
24. PDMS content affects in vitro hemocompatibility of synthetic vascular grafts
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Dario Spiller, Giorgio Soldani, Paola Losi, Silverio Sbrana, Silvia Kull, Enrica Briganti, and Ilaria Martinelli
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Adult ,Blood Platelets ,Materials science ,Platelet adhesion ,Biomedical Engineering ,Biophysics ,Peristaltic pump ,Bioengineering ,Biocompatible Materials ,Elastomer ,Hemolysis ,Monocytes ,Biomaterials ,chemistry.chemical_compound ,Silicone ,Platelet Adhesiveness ,Materials Testing ,Humans ,Platelet ,Dimethylpolysiloxanes ,Polydimethylsiloxane ,technology, industry, and agriculture ,Plasma levels ,beta-Thromboglobulin ,In vitro ,Blood Vessel Prosthesis ,Nylons ,P-Selectin ,chemistry ,Biomedical engineering - Abstract
An unsolved problem when employing small-diameter vascular grafts for aorto-coronary by-pass and peripheral reconstruction is the early thrombotic occlusion. The PEtU-PDMS is a new elastomeric material, composed of poly(ether)urethane and polydimethylsiloxane, synthesized to realize grafts with improved hemocompatibility characteristics. In order to investigate the effect of PDMS content on hemocompatibility, three different percentages of PDMS containing grafts (10, 25 and 40) were evaluated. Grafts realized with Estane 5714-F1 and silicone medical grade tubes were used as references. The hemocompatibility was investigated by an in vitro circuit in which human anticoagulated blood was circulated into grafts by a peristaltic pump modified to obtain a passive flow. For each experiment, 40 cm length graft was closed into a circular loop and put in rotation for 2 h at 37 degrees C. At the end of the experiments different parameters regarding platelet adhesion and activation were evaluated: circulating platelets count, beta-thromboglobulin release, platelet CD62P expression and amount of monocyte-platelet conjugates. PEtU-PDMS grafts with 25 and 40% of PDMS induced the lowest platelet adhesion, plasma level of beta-TG and amount of monocyte-platelet conjugates. No significative variations were observed in CD62P expression. In conclusion, PDMS content significatively affects blood-graft surface interaction, in fact higher PDMS percentage containing grafts showed the best in vitro hemocompatibility.
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- 2005
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