32 results on '"Biagioni M"'
Search Results
2. Visual impairment in FOXG1-mutated individuals and mice
- Author
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Boggio, E.M., Pancrazi, L., Gennaro, M., Lo Rizzo, C., Mari, F., Meloni, I., Ariani, F., Panighini, A., Novelli, E., Biagioni, M., Strettoi, E., Hayek, J., Rufa, A., Pizzorusso, T., Renieri, A., and Costa, M.
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- 2016
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3. Safety, efficacy and glucose turnover of reduced prandial boluses during closed-loop therapy in adolescents with type 1 diabetes: a randomized clinical trial
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Elleri, D., Biagioni, M., Allen, J. M., Kumareswaran, K., Leelarathna, L., Caldwell, K., Nodale, M., Wilinska, M. E., Haidar, A., Calhoun, P., Kollman, C., Jackson, N. C., Umpleby, A. M., Acerini, C. L., Dunger, D. B., and Hovorka, R.
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- 2015
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4. Diabetic ketoacidosis at the onset of disease during a national awareness campaign: A 2-year observational study in children aged 0-18 years
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Rabbone I., Maltoni G., Tinti D., Zucchini S., Cherubini V., Bonfanti R., Scaramuzza A., Lera R., Bobbio A., Piccinno E., Reinstadler P., Felappi B., Prandi E., Gallo F., Frongia AP., Ripoli C., Lo Presti D., Tomaselli L., Cardinale G., Stamati FA., Citriniti F., Suprani T., Graziani V., De Berardinis F., Zampolli M., De Marco R., Cavalli C., Lazzaro N., De Donno V., Toni S., Piccini B., Lenzi L., Mainetti B., Coccioli MS., d'Annunzio G., Minuto N., Aloe S., Lucchesi D., Cirillo S., Sordelli M., Del Vecchio F., Salzano LG., Meschi F., Iughetti L., Predieri B., Franzese A., Mozzillo Enza., Iafusco D., Cadario F., Savastio S., Piredda G., Cardella F., Iovane B., Calcaterra V., Berioli MG., Biagioni M., Randazzo E., Patera I., Schiaffini R., Rutigliano I., Lasagni A., Innaurato S., Gaiero A., Fichera G., Trada M., Guerraggio L., Cauvin V., Franceschi R., Tornese G., Salvatoni A., Marigliano M., Sabbion A., Maffeis C., Arnaldi C., Rabbone, I., Maltoni, G., Tinti, D., Zucchini, S., Cherubini, V., Bonfanti, R., Scaramuzza, A., Lera, R., Bobbio, A., Piccinno, E., Reinstadler, P., Felappi, B., Prandi, E., Gallo, F., Frongia, Ap., Ripoli, C., Lo Presti, D., Tomaselli, L., Cardinale, G., Stamati, Fa., Citriniti, F., Suprani, T., Graziani, V., De Berardinis, F., Zampolli, M., De Marco, R., Cavalli, C., Lazzaro, N., De Donno, V., Toni, S., Piccini, B., Lenzi, L., Mainetti, B., Coccioli, Ms., D'Annunzio, G., Minuto, N., Aloe, S., Lucchesi, D., Cirillo, S., Sordelli, M., Del Vecchio, F., Salzano, Lg., Meschi, F., Iughetti, L., Predieri, B., Franzese, A., Mozzillo, Enza., Iafusco, D., Cadario, F., Savastio, S., Piredda, G., Cardella, F., Iovane, B., Calcaterra, V., Berioli, Mg., Biagioni, M., Randazzo, E., Patera, I., Schiaffini, R., Rutigliano, I., Lasagni, A., Innaurato, S., Gaiero, A., Fichera, G., Trada, M., Guerraggio, L., Cauvin, V., Franceschi, R., Tornese, G., Salvatoni, A., Marigliano, M., Sabbion, A., Maffeis, C., Arnaldi, C., Rabbone, Ivana, Maltoni, Giulio, Tinti, Davide, Zucchini, Stefano, Cherubini, Valentino, Bonfanti, Riccardo, Scaramuzza, Andrea, Lera, Riccardo, Bobbio, Adriana, Piccinno, Elvira, Reinstadler, Petra, Felappi, Barbara, Prandi, Elena, Gallo, Francesco, Frongia, Anna Paola, Ripoli, Carlo, Lo Presti, Donatella, Tomaselli, Letizia, Cardinale, Giuliana, Stamati, Filomena Andreina, Citriniti, Felice, Suprani, Tosca, Graziani, Vanna, De Berardinis, Fiorella, Zampolli, Maria, De Marco, Rosaria, Cavalli, Claudio, Lazzaro, Nicola, De Donno, Valeria, Toni, Sonia, Piccini, Barbara, Lenzi, Lorenzo, Mainetti, Benedetta, Coccioli, Maria Susanna, D’Annunzio, Giuseppe, Minuto, Nicola, Aloe, Monica, Lucchesi, Sonia, Cirillo, Dante, Sordelli, Silvia, Delvecchio, Maurizio, Lombardo, Fortunato, Salzano, Giusy, Meschi, Franco, Iughetti, Lorenzo, Predieri, Barbara, Franzese, Adriana, Mozzillo, Enza, Iafusco, Dario, Cadario, Francesco, Savastio, Silvia, Cardella, Francesca, Iovane, Brunella, Calcaterra, Valeria, Berioli, Maria Giulia, Biagioni, Martina, Randazzo, Emioli, Patera, Ippolita Patrizia, Schiaffini, Riccardo, Rutigliano, Irene, Lasagni, Anna, Innaurato, Silvia, Gaiero, Alberto, Fichera, Grazziella, Trada, Michela, Guerraggio, Lucia, Cauvin, Vittoria, Franceschi, Roberto, Tornese, Gianluca, Salvatoni, Alessandro, Marigliano, Marco, Sabbion, Alberto, Maffeis, Claudio, and Arnaldi, Claudia
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Pediatrics ,endocrine system diseases ,Diabetic ketoacidosis ,Adolescent ,030209 endocrinology & metabolism ,Disease ,03 medical and health sciences ,0302 clinical medicine ,diabetic ketoacidosis ,Patient Education as Topic ,Diabetes mellitus ,Epidemiology ,Medicine ,Humans ,030212 general & internal medicine ,Prospective Studies ,Child ,Type 1 diabetes ,diabetes ,business.industry ,Incidence (epidemiology) ,Incidence ,epidemiology ,Infant, Newborn ,diabetic ketoacidosi ,nutritional and metabolic diseases ,Infant ,medicine.disease ,Diabetes Mellitus, Type 1 ,Italy ,diabete ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Observational study ,Female ,business ,Prevention campaign - Abstract
ObjectiveAfter a previous survey on the incidence of diabetic ketoacidosis (DKA) at onset of type 1 diabetes in children in 2013–2014 in Italy, we aimed to verify a possible decline in the incidence of DKA at onset during a national prevention campaign.DesignProspective observational study.SettingMulticentre study throughout Italy.InterventionNational awareness campaign started in November 2015 and held until December 2017.PatientsDuring 2016 and 2017 we collected data on all patients aged 0–18 years with new-onset diabetes.Main outcome measuresDKA (pH ResultsRecords (n=2361) of children with newly diagnosed type 1 diabetes were collected from 58 out of 68 (85.3%) centres of the original survey participants and 100% of the previously surveyed tertiary centres. Overall, DKA was observed in 1124 patients, with an increased rate when compared with the previous survey (47.6% vs 38.5%, p=0.002), and severe DKA in 15.3%. In children below 6 years, DKA was observed in 323 out of 617 (52.5%) and severe DKA in 16.7%; in this age group, occurrence of DKA reduced by 21.3% (p=0.009). DKA treatment according to the ISPED guidelines was adopted in 95% of the centres, with a 27% improvement (p=0.025).ConclusionsDuring a 2-year awareness campaign, DKA at onset of diabetes in children and adolescents 0–18 years is still common and increased when compared with the 2013–2014 survey.
- Published
- 2020
5. Recommendations for recognizing, risk stratifying, treating, and managing children and adolescents with hypoglycemia
- Author
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Stefano Zucchini, Stefano Tumini, Andrea Enzo Scaramuzza, Riccardo Bonfanti, Maurizio Delvecchio, Roberto Franceschi, Dario Iafusco, Lorenzo Lenzi, Enza Mozzillo, Stefano Passanisi, Claudia Piona, Ivana Rabbone, Novella Rapini, Andrea Rigamonti, Carlo Ripoli, Giuseppina Salzano, Silvia Savastio, Riccardo Schiaffini, Angela Zanfardino, Valentino Cherubini, Diabetes Study Group of the Italian Society for Pediatric Endocrinology Diabetes, Albino Claudia Accursia, Aloe Monica, Anzelotti Maria Teresa, Arnaldi Claudia, Barbetti Fabrizio, Bassi Marta, Berioli Maria Giulia, Bernardini Luca, Bertelli Enrica, Biagioni Martina, Bobbio Adriana, Bombaci Bruno, Bonfanti Riccardo, Bonura Clara, Bracciolini Giulia Patrizia, Bruzzese Mariella, Bruzzi Patrizia, Buono Pietro, Buscarino Piera, Cadario Francesco, Calcaterra Valeria, Calzi Elena, Cappa Marco, Cardani Roberta, Cardella Francesca, Cardinale Giuliana Marcella, Casertano Alberto, Castorani Valeria, Cauvin Vittoria, Cenciarelli Valentina, Ceruti Franco, Cherubini Valentino, Chiarelli Francesco, Chiari Giovanni, Cianfarani Stefano, Cicchetti Mario, Cipriano Paola, Cirillo Dante, Citriniti Felice, Coccioli Maria Susanna, Confetto Santino, Contreas Giovanna, Coro Anna, Correddu Antonella, Corsini Elisa, Crino’ Antonino, d’Annunzio Giuseppe, De Berardinis Fiorella, De Donno Valeria, De Filippo Gianpaolo, De Marco Rosaria, De Sanctis Luisa, Del Duca Elisabetta, Delvecchio Maurizio, Deodati Annalisa, Di Bonito Procolo, Di Candia Francesca, Faleschini Elena, Fattorusso Valentina, Favia Anna, Federico Giovanni, Felappi Barbara, Ferrari Mara, Ferrito Lucia, Fichera Graziella, Fontana Franco, Fornari Elena, Franceschi Roberto, Franco Francesca, Franzese Adriana, Frongia Anna Paola, Frontino Giulio, Gaiero Alberto, Galassi Sabrina Maria, Gallo Francesco, Gargantini Luigi, Giani Elisa, Gortan Anna Jolanda, Graziani Vanna, Grosso Caterina, Gualtieri Antonella, Guasti Monica, Guerraggio Lucia Paola, Guzzetti Chiara, Iafusco Dario, Iannicelli Gennaro, Iezzi Maria Laura, Ignaccolo Maria Giovanna, Innaurato Stefania, Inzaghi Elena, Iovane Brunella, Iughetti Lorenzo, Kaufmann Peter, La Loggia Alfonso, Lambertini Anna Giulia, Lapolla Rosa, Lasagni Anna, Lazzaro Nicola, Lazzeroni Pietro, Lenzi Lorenzo, Lera Riccardo, Levantini Gabriella, Lezzi Marilea, Lia Rosanna, Liguori Alice, Lo Presti Donatella, Lombardo Fortunato, Lonero Antonella, Longhi Silvia, Lorubbio Antonella, Lucchesi Sonia, Maccioni Rosella, Macedoni Maddalena, Macellaro Patrizia Cristiana, Madeo Simona Filomena, Maffeis Claudio, Mainetti Benedetta, Maltoni Giulio, Mameli Chiara, Mammì Francesco, Manca Bitti Maria Luisa, Mancioppi Valentina, Manco Melania, Marigliano Marco, Marino Monica, Marsciani Alberto, Matteoli Maria Cristina, Mazzali Elena, Minute Marta, Minuto Nicola, Monti Sara, Morandi Anita,, Morganti Gianfranco, Morotti Elisa, Mozzillo Enza, Musolino Gianluca, Olivieri Francesca, Ortolani Federica, Pampanini Valentina, Pardi Daniela, Pascarella Filomena, Pasquino Bruno, Passanisi Stefano, Patera Ippolita Patrizia, Pedini Annalisa, Pennati Maria Cristina, Peruzzi Sonia, Peverelli Paola, Pezzino Giulia, Piccini Barbara, Piccinno Elvira Eugenia Rosaria, Piona Claudia, Piredda Gavina, Piscopo Alessia, Pistone Carmelo, Pozzi Erica, Prandi Elena, Predieri Barbara, Prudente Sabrina, Pulcina Anna, Rabbone Ivana, Randazzo Emioli, Rapini Novella, Reinstadler Petra, Riboni Sara, Ricciardi Maria Rossella, Rigamonti Andrea, Ripoli Carlo, Rossi Virginia, Rossi Paolo, Rutigliano Irene, Sabbion Alberto, Salvatoni Alessandro, Salvo Caterina, Salzano Giuseppina, Sanseviero Mariateresa, Savastio Silvia, Savini Rosanna, Scanu Mariapiera, Scaramuzza Andrea Enzo, Schiaffini Riccardo, Schiavone Maurizio, Schieven Eleonardo, Scipione Mirella, Secco Andrea, Silvestri Francesca, Siri Giulia, Sogno Valin Paola, Sordelli Silvia, Spiri Daniele, Stagi Stefano, Stamati Filomena Andreina, Suprani Tosca, Talarico Valentina, Tiberi Valentina, Timpanaro Tiziana Antonia Lucia, Tinti Davide, Tirendi Antonina, Tomaselli Letizia Grazia, Toni Sonia, Torelli Cataldo, Tornese Gianluca, Trada Michela,, Trettene Adolfo Andrea, Tumini Stefano, Tumminelli Marilena, Valerio Giuliana, Vandelli Sara, Ventrici Claudia, Zampolli Maria, Zanatta Manuela, Zanfardino Angela, Zecchino Clara, Zonca Silvia, and Zucchini Stefano
- Subjects
adolescents ,automated insulin delivery ,children ,hypoglycemia ,glucagon ,oral glucose ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
There has been continuous progress in diabetes management over the last few decades, not least due to the widespread dissemination of continuous glucose monitoring (CGM) and automated insulin delivery systems. These technological advances have radically changed the daily lives of people living with diabetes, improving the quality of life of both children and their families. Despite this, hypoglycemia remains the primary side-effect of insulin therapy. Based on a systematic review of the available scientific evidence, this paper aims to provide evidence-based recommendations for recognizing, risk stratifying, treating, and managing patients with hypoglycemia. The objective of these recommendations is to unify the behavior of pediatric diabetologists with respect to the timely recognition and prevention of hypoglycemic episodes and the correct treatment of hypoglycemia, especially in patients using CGM or advanced hybrid closed-loop systems. All authors have long experience in the specialty and are members of the Italian Society of Pediatric Endocrinology and Diabetology. The goal of treating hypoglycemia is to raise blood glucose above 70 mg/dL (3.9 mmol/L) and to prevent further decreases. Oral glucose at a dose of 0.3 g/kg (0.1 g/kg for children using “smart pumps” or hybrid closed loop systems in automated mode) is the preferred treatment for the conscious individual with blood glucose
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- 2024
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6. Neural correlates of visuospatial dysfunction in Parkinson's Disease: A multimodal biomarker study
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Cucca, A., primary, Mania, D., additional, Sharma, K., additional, Acosta, I., additional, Berberian, M., additional, Beheshti, M., additional, Biagioni, M., additional, Droby, A., additional, Di Rocco, A., additional, Ghilardi, M.F., additional, Inglese, M., additional, Rizzo, J.R., additional, and Feigin, A., additional
- Published
- 2020
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7. Effect of hydrolyzed infant formula vs conventional formula on risk of type 1 diabetes the TRIGR randomized clinical trial
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Knip M., Akerblom H. K., Altaji E., Becker D., Bruining J., Castano L., Danne T., De Beaufort C., Dosch H. -M., Dupre J., Fraser W. D., Howard N., Ilonen J., Konrad D., Kordonouri O., Krischer J. P., Lawson M. L., Ludvigsson J., Madacsy L., Mahon J. L., Ormisson A., Palmer J. P., Pozzilli P., Savilahti E., Serrano-Rios M., Songini M., Taback S., Vaarala O., White N. H., Virtanen S. M., Wasikowa R., Mandrup-Poulsen T., Arjas E., Lernmark A., Laara E., Schmidt B., Hyytinen M., Koski K., Koski M., Merentie K., Pajakkala E., Reunanen A., Salonen M., Terhonen T., Virkkunen S., Cuthbertson D., Gainer B., Hadley D., Malloy J., Nallamshetty L., Shanker L., Bradley B., Lough G., Fraser W., Sermer M., Taback S. P., Franciscus M., Nucci A., Palmer J., Alahuhta K., Barlund S., Korhonen T., Kovanen L., Lehtonen E., Niinisto S., Pekkala M., Sorkio S., Toivanen L., Vahatalo L., Uusitalo U., Ohman T., Bongiorno R., Catteau J., Fraser G., Lloyd M., Crock P., Giles M., Siech K., See D. W., Brown C., Craig M., Johnston A., Bere L. J., Clarson C. L., Jenner M., McManus R., Renato N., Lovell M., Higo D., Kent N., Kwan J., Marshall C., Metzger D., Chanoine J. -P., Stewart L., Thompson D., Edwards A., Lange I., Mercer J., Pacaud D., Josephine H., Schwarz W., Stephure D. K., Boer J., Chatur T., Chick C., Couch B., Demianczuk N., Girgis R., Marks S., Ryan E., Thompson M., Dean H. J., Grant L., Hamelin K., LaForte J., Murphy L., Catte D., Schneider C., Sellers E. A. C., Woo V., Boland A., Clark H. D., Cooper T., Gruslin A., Karovitch A., Keely E., Malcolm J. C., Sauro V., Tawagi G. F., Andrighetti S., Arnold G., Barrett J., Blumer I., Daneman D., Donat D., Ehrlich R., Feig D., Gottesman I., Gysler M., Karkanis S., Kenshole A., Knight B., Lackie E., Lewis V., Martin M. J., Maxwell C., Oliver G., Panchum P., Shilletto N., Simone A., Skidmore M., Turrini T., Wong S., Allen C., Belanger L., Bouchard I., Ferland S., Frenette L., Garrido-Russo M., Leblanc M., Imbeault J., Morin V., Olivier G., Weisnagell J., Costain G., Dornan J., Heath K., MacSween M. -C., McGibbon A., Ramsay C., Sanderson F., Sanderson S., Benabdesselam L., Gonthier M., Huot C., Thibeault M., Laforte D., Legault L., Perron P., Armson A., Canning P., Cummings E. A., Ivanko V., McLeod L., Mokashi A., Scott K., Bridger T., Crane J., Crummell C., Curtis J. C., Dawson C., Joyce C., Newhook L. A., Newman S., Druken E., Begum-Hasan J., Breen A., Houlden R., Woods M., Carrson G., Kelly S., Martel M. J., Penner M., Sankaran K., Hardy-Brown K., King N., White R. A., Park M., Popkin J., Robson L., Coles K., Al Taji E., Cerna M., Cerny M., Francova H., Hainerova I., Kothankova H., Koukalova R., Krakorova V., Mendlova P., Sitova R., Stechova K., Vavrinec J., Vosahlo J., Zlatohlavkova B., Brazdova L., Faksova P., Gregorova D., Kantor L., Malkova K., Venhacova J., Venhacova P., Cipra A., Skvor J., Budejovice C., Tomsikova Z., Botkova-Krauseova H., Mockova A., Paterova P., Gogelova P., Kandrnalova J., Einberg U., Jakovlev U., Posiadlo S., Rannaste E., Raukas R., Riikjarv M. -A., Valla K., Astover V., Kirss A., Retpap J., Taht E., Tillmann V., Vahtra S., Heikkila M., Hirvasniemi M., Luopajarvi K., Johansson S., Kleemola P., Laukkanen E., Parkkola A., Pigg H. -M., Puttonen H., Renlund M., Salonen K., Suomalainen H., Tenkula T., Teramo K., Jarvenpaa A. -L., Hamalainen A. -M., Jussila R., Kiiveri S., Haavisto H., Holopainen S., Kupiainen H., Leeve T., Lumme K., Nironen T., Tenhola S., Tiilikainen T., Keinonen H., Lautala P., Salonen P., Vesanto M., Aspholm A. S., Asunta P., Ikavalko H., Jason E., Jaminki S., Kekki P., Koskinen M., Lehtimaki S., Lahde J., Makela M., Peltoniemi S., Poutiainen L., Ranta K., Salonsaari T., Sarviharju-Tujula S. -L., Selvenius J., Siljander H., Haanpaa P. -L., Holm C., Juutilainen A., Jarvelainen V., Kangaskolkka-Keskilohko A. -M., Laino E., Marjamaki L., Suominen E., Ylitalo S., Hokkanen M., Lounamaa R., Matikainen M., Nuuja A., Paalanen I., Puupponen A. R., Salo-Edwards H., Alanne S., Kultti T., Linjama H., Muhonen K., Vaaraniemi M., Talvitie T., Backman M., Hanhijarvi R., Koivula P., Lindstrom K., Martikainen A., Nurmi P., Bjork A., Huopio H., Komulainen J., Lehtomaki S., Muikku E., Pesola J., Sankilampi U., Arkkola T., Hekkala A., Jurvakainen S., Koivikko M. -L., Kahonen M., Leinonen E., Mykkanen T., Pohjola H., Riikonen K., Niittyvuopio A., Stenius A., Tapanainen P., Veijola R., Alar A., Jovio S., Korpela P., Makinen E., Hietanen L., Kivisto J., Kaar M. -L., Lehtimaki P., Mustila T., Popov E., Saatela S., Taittonen L., Ahtiainen K., Laaksonen N., Luoto M., Viitala J., Virransalo R., Nykanen P., Paajanen S., Parkkinen S., Pyrhonen H., Sarkka T., Aschemeier B., Bektas S., Biester T., Datz N., Deiss D., Fath M., Lupke K., Muller B., Nestoris C., Rothes S., Sadeghian E., Semler K., Arato A., Krikovszky D., Nobilis A., Szenasi J., Benevento D., Anguissola G. B., Biagioni M., Bizzarri C., Cherubini V., Ferrito L., Giordano C., Giorgetti C., Khazrai Y. M., Kyanvash S., Maddaloni E., Napoli A., Piergiovanni F., Pitocco D., Suraci T., Tabacco G., Valente L., Visalli N., Carboni M. B., Cavallo R., Cau V., Isola C., Ledda A., Loddo M., Mannu C., Pettinau M., Pisano S., Porceddu M., Putzu C., Rita A., Peters D., Schierloh U., Bisschoff M., Blonk L., Lappenschaar T., Manai B., Seesink M., Sperling-Conrad M., Verhagen M., Zoethout J. A., Basiak A., Chalas M., Chesiak M., Gramza A., Iwankiewicz J., Sieradzan E., Wikiera B., Ciechanowska M., Dziatkowiak H., Futona B., Gorska A., Glowacka-Wony M., Kaim I., Klich B., Starzyk J., Wolanin M., Tokarska L., Chucherco D., Deja G., Firek-Pedras M., Jarosz-Chobot P., Kalina M., Kutrowska-Adamusiak K., Minkina-Pedras M., Muchaka-Bianga M., Bodalski J., Mlynarski W., Szadkowska A., Cieslak A., Cypryk K., Dziatosz K., Jastzebowska J., Krysiak A., Szymanska U., Wilcznski J., Zawodniak-Szalapska M., Aguay A., Bilbao J. R., Chueca M., Cortazar A., Echarte G., Frutos T. G., Jimenez P., Martul P., Moreno A., Oyarzabal M., Rica I., Salgado Y., Martinez-Larrad M. T., Hawkins F. G., Hernandez R., Herranz L., Pallardo L. F., Deibarra L. S., Fernandez B. H., Luis J. L., Ortiz-Quintana L., Recarte P. P., Arnau D. R., Aronsson L., Boden S., Fredriksson J., Isacsson E., Johansson I., Karlsson E., Lock C., Sandstrom A. -M., Konefal M. S., Andreasson C., Dahlstrom U., Hanas R., Lundqvist K., Windell L., Jansson I., Karlsson A. -K., Lindbladh B., Odenman I., Pettersson C., Sundberg F., Sundqvist M., Aronsson S., Bellman I., Bengtsson A. -B., Lyden G. -B., Nilsson N. -O., Soderblom M., Unt C., Augustsson M., Bengtsson M., Fors H., Helmrich A., Johansson T. O., Andersson A. -C., Boiard-Stomlid A., Hellgren G., Kallsholm H., Lindqvist J., Nilsson M., Nordwall M., Stromstedt C., Ahsberg C., Lindh A., Lindhe C., Samuelsson C., Wiik A., Edenwall H., Ljumgcrantz M., Persson I. -B., Strigard E., Svensson B. -L., Aman J., Breivik G. -E., Detlofsson I. -L., Kroon M., Sarnblad S., Johansson C., Ilvered R., Lundberg A., Akesson K., Beccarelli A., Gadient M., Rappold-Amrein C., Schoenle E., Daftary A., Damagro-Elias M. E., Gilmour C., Klein M. B., Lain C., Salerno D., Smith M. E., Vats K., Pfaff D. J., Malone P., Mansfield P., Munns M., Nickel K., Pompilio K., Siemion W., Taculad R., Van Horn K., Zdanadewic M., Chambliss C., Jones J., Sadler M., Tanner-Blasiar M., Bell C., Camper N., Devaskar S., Devaskar U., Horowitz H., Rogers L., Shannahan R., Silk K., Bermudez Z., Colon R., Frazer T., Martinez-Nieves B., Torres J., Vega J., Chan M., Cook S., Goland R., Greenberg E., Jules N., Montes J., Nelson M., Parra-Valencia Z., Schachner H., Softness B., Kiviniemi M., Suomenin R., Alexander A., Hyrckowian E., Nichol L., Trucco M., Karjalainen E., Louhio T., Sarnesto A., Valtonen E., Davydova B., Helander S., Hamalainen J., Harkonen T., Joutsjoki L., Kararic M., Latva-Koivisto M., Lonn E., Nurmi T., Ollila I., Rinkinen J., Ronkainen M., Tukiainen H., Cederlof A., Kiikeri M., Tsupari S., Cheng R., Bryant K., Chan Y., Maezawa Y., Paltser G., Rasavi R., Tsui H., Winer S., Wu P., Yantha J., Pediatrics, Knip M., Akerblom H.K., Altaji E., Becker D., Bruining J., Castano L., Danne T., De Beaufort C., Dosch H.-M., Dupre J., Fraser W.D., Howard N., Ilonen J., Konrad D., Kordonouri O., Krischer J.P., Lawson M.L., Ludvigsson J., Madacsy L., Mahon J.L., Ormisson A., Palmer J.P., Pozzilli P., Savilahti E., Serrano-Rios M., Songini M., Taback S., Vaarala O., White N.H., Virtanen S.M., Wasikowa R., Mandrup-Poulsen T., Arjas E., Lernmark A., Laara E., Schmidt B., Hyytinen M., Koski K., Koski M., Merentie K., Pajakkala E., Reunanen A., Salonen M., Terhonen T., Virkkunen S., Cuthbertson D., Gainer B., Hadley D., Malloy J., Nallamshetty L., Shanker L., Bradley B., Lough G., Fraser W., Sermer M., Taback S.P., Franciscus M., Nucci A., Palmer J., Alahuhta K., Barlund S., Korhonen T., Kovanen L., Lehtonen E., Niinisto S., Pekkala M., Sorkio S., Toivanen L., Vahatalo L., Uusitalo U., Ohman T., Bongiorno R., Catteau J., Fraser G., Lloyd M., Crock P., Giles M., Siech K., See D.W., Brown C., Craig M., Johnston A., Bere L.J., Clarson C.L., Jenner M., McManus R., Renato N., Lovell M., Higo D., Kent N., Kwan J., Marshall C., Metzger D., Chanoine J.-P., Stewart L., Thompson D., Edwards A., Lange I., Mercer J., Pacaud D., Josephine H., Schwarz W., Stephure D.K., Boer J., Chatur T., Chick C., Couch B., Demianczuk N., Girgis R., Marks S., Ryan E., Thompson M., Dean H.J., Grant L., Hamelin K., LaForte J., Murphy L., Catte D., Schneider C., Sellers E.A.C., Woo V., Boland A., Clark H.D., Cooper T., Gruslin A., Karovitch A., Keely E., Malcolm J.C., Sauro V., Tawagi G.F., Andrighetti S., Arnold G., Barrett J., Blumer I., Daneman D., Donat D., Ehrlich R., Feig D., Gottesman I., Gysler M., Karkanis S., Kenshole A., Knight B., Lackie E., Lewis V., Martin M.J., Maxwell C., Oliver G., Panchum P., Shilletto N., Simone A., Skidmore M., Turrini T., Wong S., Allen C., Belanger L., Bouchard I., Ferland S., Frenette L., Garrido-Russo M., Leblanc M., Imbeault J., Morin V., Olivier G., Weisnagell J., Costain G., Dornan J., Heath K., MacSween M.-C., McGibbon A., Ramsay C., Sanderson F., Sanderson S., Benabdesselam L., Gonthier M., Huot C., Thibeault M., Laforte D., Legault L., Perron P., Armson A., Canning P., Cummings E.A., Ivanko V., McLeod L., Mokashi A., Scott K., Bridger T., Crane J., Crummell C., Curtis J.C., Dawson C., Joyce C., Newhook L.A., Newman S., Druken E., Begum-Hasan J., Breen A., Houlden R., Woods M., Carrson G., Kelly S., Martel M.J., Penner M., Sankaran K., Hardy-Brown K., King N., White R.A., Park M., Popkin J., Robson L., Coles K., Al Taji E., Cerna M., Cerny M., Francova H., Hainerova I., Kothankova H., Koukalova R., Krakorova V., Mendlova P., Sitova R., Stechova K., Vavrinec J., Vosahlo J., Zlatohlavkova B., Brazdova L., Faksova P., Gregorova D., Kantor L., Malkova K., Venhacova J., Venhacova P., Cipra A., Skvor J., Budejovice C., Tomsikova Z., Botkova-Krauseova H., Mockova A., Paterova P., Gogelova P., Kandrnalova J., Einberg U., Jakovlev U., Posiadlo S., Rannaste E., Raukas R., Riikjarv M.-A., Valla K., Astover V., Kirss A., Retpap J., Taht E., Tillmann V., Vahtra S., Heikkila M., Hirvasniemi M., Luopajarvi K., Johansson S., Kleemola P., Laukkanen E., Parkkola A., Pigg H.-M., Puttonen H., Renlund M., Salonen K., Suomalainen H., Tenkula T., Teramo K., Jarvenpaa A.-L., Hamalainen A.-M., Jussila R., Kiiveri S., Haavisto H., Holopainen S., Kupiainen H., Leeve T., Lumme K., Nironen T., Tenhola S., Tiilikainen T., Keinonen H., Lautala P., Salonen P., Vesanto M., Aspholm A.S., Asunta P., Ikavalko H., Jason E., Jaminki S., Kekki P., Koskinen M., Lehtimaki S., Lahde J., Makela M., Peltoniemi S., Poutiainen L., Ranta K., Salonsaari T., Sarviharju-Tujula S.-L., Selvenius J., Siljander H., Haanpaa P.-L., Holm C., Juutilainen A., Jarvelainen V., Kangaskolkka-Keskilohko A.-M., Laino E., Marjamaki L., Suominen E., Ylitalo S., Hokkanen M., Lounamaa R., Matikainen M., Nuuja A., Paalanen I., Puupponen A.R., Salo-Edwards H., Alanne S., Kultti T., Linjama H., Muhonen K., Vaaraniemi M., Talvitie T., Backman M., Hanhijarvi R., Koivula P., Lindstrom K., Martikainen A., Nurmi P., Bjork A., Huopio H., Komulainen J., Lehtomaki S., Muikku E., Pesola J., Sankilampi U., Arkkola T., Hekkala A., Jurvakainen S., Koivikko M.-L., Kahonen M., Leinonen E., Mykkanen T., Pohjola H., Riikonen K., Niittyvuopio A., Stenius A., Tapanainen P., Veijola R., Alar A., Jovio S., Korpela P., Makinen E., Hietanen L., Kivisto J., Kaar M.-L., Lehtimaki P., Mustila T., Popov E., Saatela S., Taittonen L., Ahtiainen K., Laaksonen N., Luoto M., Viitala J., Virransalo R., Nykanen P., Paajanen S., Parkkinen S., Pyrhonen H., Sarkka T., Aschemeier B., Bektas S., Biester T., Datz N., Deiss D., Fath M., Lupke K., Muller B., Nestoris C., Rothes S., Sadeghian E., Semler K., Arato A., Krikovszky D., Nobilis A., Szenasi J., Benevento D., Anguissola G.B., Biagioni M., Bizzarri C., Cherubini V., Ferrito L., Giordano C., Giorgetti C., Khazrai Y.M., Kyanvash S., Maddaloni E., Napoli A., Piergiovanni F., Pitocco D., Suraci T., Tabacco G., Valente L., Visalli N., Carboni M.B., Cavallo R., Cau V., Isola C., Ledda A., Loddo M., Mannu C., Pettinau M., Pisano S., Porceddu M., Putzu C., Rita A., Peters D., Schierloh U., Bisschoff M., Blonk L., Lappenschaar T., Manai B., Seesink M., Sperling-Conrad M., Verhagen M., Zoethout J.A., Basiak A., Chalas M., Chesiak M., Gramza A., Iwankiewicz J., Sieradzan E., Wikiera B., Ciechanowska M., Dziatkowiak H., Futona B., Gorska A., Glowacka-Wony M., Kaim I., Klich B., Starzyk J., Wolanin M., Tokarska L., Chucherco D., Deja G., Firek-Pedras M., Jarosz-Chobot P., Kalina M., Kutrowska-Adamusiak K., Minkina-Pedras M., Muchaka-Bianga M., Bodalski J., Mlynarski W., Szadkowska A., Cieslak A., Cypryk K., Dziatosz K., Jastzebowska J., Krysiak A., Szymanska U., Wilcznski J., Zawodniak-Szalapska M., Aguay A., Bilbao J.R., Chueca M., Cortazar A., Echarte G., Frutos T.G., Jimenez P., Martul P., Moreno A., Oyarzabal M., Rica I., Salgado Y., Martinez-Larrad M.T., Hawkins F.G., Hernandez R., Herranz L., Pallardo L.F., Deibarra L.S., Fernandez B.H., Luis J.L., Ortiz-Quintana L., Recarte P.P., Arnau D.R., Aronsson L., Boden S., Fredriksson J., Isacsson E., Johansson I., Karlsson E., Lock C., Sandstrom A.-M., Konefal M.S., Andreasson C., Dahlstrom U., Hanas R., Lundqvist K., Windell L., Jansson I., Karlsson A.-K., Lindbladh B., Odenman I., Pettersson C., Sundberg F., Sundqvist M., Aronsson S., Bellman I., Bengtsson A.-B., Lyden G.-B., Nilsson N.-O., Soderblom M., Unt C., Augustsson M., Bengtsson M., Fors H., Helmrich A., Johansson T.O., Andersson A.-C., Boiard-Stomlid A., Hellgren G., Kallsholm H., Lindqvist J., Nilsson M., Nordwall M., Stromstedt C., Ahsberg C., Lindh A., Lindhe C., Samuelsson C., Wiik A., Edenwall H., Ljumgcrantz M., Persson I.-B., Strigard E., Svensson B.-L., Aman J., Breivik G.-E., Detlofsson I.-L., Kroon M., Sarnblad S., Johansson C., Ilvered R., Lundberg A., Akesson K., Beccarelli A., Gadient M., Rappold-Amrein C., Schoenle E., Daftary A., Damagro-Elias M.E., Gilmour C., Klein M.B., Lain C., Salerno D., Smith M.E., Vats K., Pfaff D.J., Malone P., Mansfield P., Munns M., Nickel K., Pompilio K., Siemion W., Taculad R., Van Horn K., Zdanadewic M., Chambliss C., Jones J., Sadler M., Tanner-Blasiar M., Bell C., Camper N., Devaskar S., Devaskar U., Horowitz H., Rogers L., Shannahan R., Silk K., Bermudez Z., Colon R., Frazer T., Martinez-Nieves B., Torres J., Vega J., Chan M., Cook S., Goland R., Greenberg E., Jules N., Montes J., Nelson M., Parra-Valencia Z., Schachner H., Softness B., Kiviniemi M., Suomenin R., Alexander A., Hyrckowian E., Nichol L., Trucco M., Karjalainen E., Louhio T., Sarnesto A., Valtonen E., Davydova B., Helander S., Hamalainen J., Harkonen T., Joutsjoki L., Kararic M., Latva-Koivisto M., Lonn E., Nurmi T., Ollila I., Rinkinen J., Ronkainen M., Tukiainen H., Cederlof A., Kiikeri M., Tsupari S., Cheng R., Bryant K., Chan Y., Maezawa Y., Paltser G., Rasavi R., Tsui H., Winer S., Wu P., Yantha J., University of Zurich, and Knip, Mikael
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Male ,Risk ,medicine.medical_specialty ,Casein ,Breastfeeding ,030209 endocrinology & metabolism ,610 Medicine & health ,2700 General Medicine ,Endocrinology and Diabetes ,Disease-Free Survival ,law.invention ,Follow-Up Studie ,Nutrition Policy ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Double-Blind Method ,SDG 3 - Good Health and Well-being ,law ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Cumulative incidence ,030212 general & internal medicine ,Child ,Infant Nutritional Physiological Phenomena ,Original Investigation ,2. Zero hunger ,Type 1 diabetes ,business.industry ,Hazard ratio ,Absolute risk reduction ,Infant, Newborn ,Caseins ,General Medicine ,ta3121 ,medicine.disease ,Infant Formula ,3. Good health ,Diabetes Mellitus, Type 1 ,Infant formula ,10036 Medical Clinic ,Endokrinologi och diabetes ,Female ,business ,Human ,Follow-Up Studies - Abstract
IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cows milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. MAIN OUTCOMES AND MEASURES Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8%[95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes. Funding Agencies|Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health [HD040364, HD042444, HD051997]; Canadian Institutes of Health Research; Commission of the European Communities [QLK1-2002-00372]; European Foundation for the Study of Diabates/JDRF/Novo Nordisk; Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research) [250114]; Dutch Diabetes Research Foundation; Finnish Diabetes Research Foundation; JDRF
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- 2018
8. Insulin pump failures in Italian children with Type 1 diabetes: retrospective 1-year cohort study
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Rabbone, I., Minuto, N., Bonfanti, R., Marigliano, M., Cerutti, F., Cherubini, V., d(')Annunzio, G., Frongia, A. P., Iafusco, D., Ignaccolo, G., Lombardo, F., Schiaffini, R., Toni, S., Tumini, S., Zucchini, S., Pistorio, A., Scaramuzza, A. E., Scaramuuzza, A. E., Lera, R., Secco, A., Bobbio, A., Bechaz, M., Piccinno, E., Natale, M. P., Ortolani, F., Zecchino, C., Lonero, A., Maltoni, G., Pasquino, B., Gallo, F., Frongia, P., Ripoli, C., Lo Presti, D., Timpanaro, T., Citriniti, F., Suprani, T., Carinci, S., Cipriano, P., Lazzaro, N., De Donno, V., Gallarotti, F., Lenzi, L., Piccini, B., Vittorio, L., Russo, C., Borea, R., Mamm(`i), F., Bruzzese, M., Ventrici, C., Salzano, G., Frontino, G., Bonura, C., Favalli, V., Scaramuzza, A., Zuccotti, G. V., Ferrari, M., Iughetti, L., Predieri, B., Franzese, A., Mozzillo, E., Buono, P., Confetto, S., Zanfardino, A., Cadario, F., Savastio, S., Fiorito, C., Barbieri, P., Piredda, G., Cardella, F., Ropolo, R., Federico, G., Marchi, B., Benevento, D., Carducci, C., Mancabitti, M. L., Delvecchio, M., Lapolla, R., Gaiero, A., Fichera, G., Ignaccolo, M. G., Tinti, D., Cauvin, V., Franceschi, R., Biagioni, M., Salvatoni, A., Scolari, A., Maffeis, C., Sabbion, A., Arnaldi, C., Tosini, D., Rabbone, I, Minuto, N., Bonfanti, R., Marigliano, M., Cerutti, F., Cherubini, V., D'Annunzio, G., Frongia, A. P., Iafusco, Dario, Ignaccolo, G., Lombardo, F., Schiaffini, R., Toni, S., Tumini, S., Zucchini, S., Pistorio, A., Scaramuzza, A. E., Rabbone, I., Iafusco, D., Lera, R., Secco, A., Bobbio, A., Bechaz, M., Piccinno, E., Natale, M. P., Ortolani, F., Zecchino, C., Lonero, A., Maltoni, G., Pasquino, B., Gallo, F., Frongia, P., Ripoli, C., Lo Presti, D., Timpanaro, T., Citriniti, F., Suprani, T., Carinci, S., Cipriano, P., Lazzaro, N., De Donno, V., Gallarotti, F., Lenzi, L., Piccini, B., Vittorio, L., Russo, C., Borea, R., Mammi, F., Bruzzese, M., Ventrici, C., Salzano, G., Frontino, G., Bonura, C., Favalli, V., Scaramuzza, A., Zuccotti, G. V., Ferrari, M., Iughetti, L., Predieri, B., Franzese, A., Mozzillo, E., Buono, P., Confetto, S., Zanfardino, A., Cadario, F., Savastio, S., Fiorito, C., Barbieri, P., Piredda, G., Cardella, F., Ropolo, R., Federico, G., Marchi, B., Benevento, D., Carducci, C., Mancabitti, M. L., Del Vecchio, M., Lapolla, R., Gaiero, A., Fichera, G., Ignaccolo, M. G., Tinti, D., Cauvin, V., Franceschi, R., Biagioni, M., Salvatoni, A., Scolari, A., Maffeis, C., Sabbion, A., Arnaldi, C., Tosini, D., Rabbone, Minuto, Mammì, F., and Mozzillo, Enza.
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Blood Glucose ,Male ,Pediatrics ,Adolescent ,Blood Glucose Self-Monitoring ,Child ,Child, Preschool ,Diabetes Mellitus, Type 1 ,Equipment Failure ,Female ,Humans ,Infant ,Insulin ,Italy ,Retrospective Studies ,Insulin Infusion Systems ,type 1 diabetes ,medicine.medical_treatment ,Endocrinology, Diabetes and Metabolism ,Internal Medicine ,Endocrinology ,0302 clinical medicine ,Retrospective Studie ,Medicine ,030212 general & internal medicine ,Diabetes ,Diabetology ,failure ,Diabetes and Metabolism ,children and adolescents ,insulin pump ,Cohort study ,Type 1 ,Human ,Insulin pump ,medicine.medical_specialty ,Disease duration ,030209 endocrinology & metabolism ,03 medical and health sciences ,Diabetes mellitus ,Diabetes Mellitus ,Preschool ,Type 1 diabetes ,business.industry ,Diabetes, Type1, Pump, Insulin ,Type1 ,Retrospective cohort study ,Pump ,medicine.disease ,Surgery ,Insulin Infusion System ,business - Abstract
Aims Insulin pump failure and/or malfunction requiring replacement have not been thoroughly investigated. This study evaluated pump replacement in children and adolescents with Type 1 diabetes using insulin pump therapy. Methods Data were collected for all participants younger than 19 years, starting insulin pump therapy before 31 December 2013. For each child, age, disease duration, date of insulin pump therapy initiation, insulin pump model, failure/malfunction/replacement yes/no and reason were considered for the year 2013. Results Data were returned by 40 of 43 paediatric centres belonging to the Diabetes Study Group of the Italian Society of Paediatric Endocrinology and Diabetology. In total, 1574 of 11 311 (13.9%) children and adolescents with Type 1 diabetes were using an insulin pump: 29.2% Animas VIBE™, 9.4% Medtronic MiniMed 715/515™, 34.3% Medtronic MiniMed VEO™, 24.3% Accu-Check Spirit Combo™ and 2.8% other models. In 2013, 0.165 insulin pump replacements per patient-year (11.8% due to pump failure/malfunction and 4.7% due to accidental damage) were recorded. Animas VIBE™ (22.1%) and Medtronic MiniMed VEO™ (17.7%) were the most replaced. Conclusions In a large cohort of Italian children and adolescents with Type 1 diabetes, insulin pump failure/malfunction and consequent replacement are aligned with rates previously reported and higher in more sophisticated pump models. This article is protected by copyright. All rights reserved.
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- 2017
9. Comorbid Normal Pressure Hydrocephalus with Parkinsonism: A Clinical Challenge and Call for Awareness
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Cucca, A., Biagioni, M. C., Sharma, K., Golomb, J., Gilbert, R. M., Di Rocco, A., and Fleisher, J. E.
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Article Subject - Abstract
Idiopathic normal pressure hydrocephalus (iNPH) is the most common cause of hydrocephalus in adults. The diagnosis may be challenging, requiring collaborative efforts between different specialists. According to the International Society for Hydrocephalus and Cerebrospinal Fluid Disorders, iNPH should be considered in the differential of any unexplained gait failure with insidious onset. Recognizing iNPH can be even more difficult in the presence of comorbid neurologic disorders. Among these, idiopathic Parkinson’s disease (PD) is one of the major neurologic causes of gait dysfunction in the elderly. Both conditions have their peak prevalence between the 6th and the 7th decade. Importantly, postural instability and gait dysfunction are core clinical features in both iNPH and PD. Therefore, diagnosing iNPH where diagnostic criteria of PD have been met represents an additional clinical challenge. Here, we report a patient with parkinsonism initially consistent with PD who subsequently displayed rapidly progressive postural instability and gait dysfunction leading to the diagnosis of concomitant iNPH. In the following sections, we will review the clinical features of iNPH, as well as the overlapping and discriminating features when degenerative parkinsonism is in the differential diagnosis. Understanding and recognizing the potential for concomitant disease are critical when treating both conditions.
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- 2018
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10. P021 Differential clinical and neurophysiological outcomes after premotor rTMS in Parkinson’s disease
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Biagioni, M., primary, Son, A., additional, Agarwal, S., additional, Gilbert, R., additional, Quartarone, A., additional, and DiRocco, A., additional
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- 2017
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11. Safety, efficacy and glucose turnover of reduced prandial boluses during closed-loop therapy in adolescents with type 1 diabetes: a randomized clinical trial
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Elleri, D, Biagioni, M, Allen, JM, Kumareswaran, K, Leelarathna, L, Caldwell, K, Nodale, M, Wilinska, ME, Haidar, A, Calhoun, P, Kollman, C, Jackson, NC, Umpleby, AM, Acerini, CL, Dunger, DB, Hovorka, R, Nodale, Marianna [0000-0002-0333-8918], Wilinska, Gosia [0000-0003-2739-1753], Acerini, Carlo [0000-0003-2121-5871], Dunger, David [0000-0002-2566-9304], Hovorka, Roman [0000-0003-2901-461X], and Apollo - University of Cambridge Repository
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Blood Glucose ,Male ,Risk ,Cross-Over Studies ,Adolescent ,type 1 diabetes ,Injections, Subcutaneous ,Glycemic Load ,Drug Administration Schedule ,Hypoglycemia ,Diabetes Mellitus, Type 1 ,Insulin Infusion Systems ,England ,Hyperinsulinism ,postprandial hypoglycaemia ,closed-loop insulin delivery ,Humans ,Hypoglycemic Agents ,Insulin ,Female ,Insulin Resistance ,Meals ,Algorithms ,Monitoring, Physiologic - Abstract
AIMS: To evaluate safety, efficacy and glucose turnover during closed-loop with meal announcement using reduced prandial insulin boluses in adolescents with type 1 diabetes (T1D). METHODS: We conducted a randomized crossover study comparing closed-loop therapy with standard prandial insulin boluses versus closed-loop therapy with prandial boluses reduced by 25%. Eight adolescents with T1D [3 males; mean (standard deviation) age 15.9 (1.5) years, glycated haemoglobin 74 (17) mmol/mol; median (interquartile range) total daily dose 0.9 (0.7, 1.1) IU/kg/day] were studied on two 36-h-long visits. In random order, subjects received closed-loop therapy with either standard or reduced insulin boluses administered with main meals (50-80 g carbohydrates) but not with snacks (15-30 g carbohydrates). Stable-label tracer dilution methodology measured total glucose appearance (Ra_total) and glucose disposal (Rd). RESULTS: The median (interquartile range) time spent in target (3.9-10 mmol/l) was similar between the two interventions [74 (66, 84)% vs 80 (65, 96)%; p = 0.87] as was time spent above 10 mmol/l [21.8 (16.3, 33.5)% vs 18.0 (4.1, 34.2)%; p = 0.87] and below 3.9 mmol/l [0 (0, 1.5)% vs 0 (0, 1.8)%; p = 0.88]. Mean plasma glucose was identical during the two interventions [8.4 (0.9) mmol/l; p = 0.98]. Hypoglycaemia occurred once 1.5 h post-meal during closed-loop therapy with standard bolus. Overall insulin delivery was lower with reduced prandial boluses [61.9 (55.2, 75.0) vs 72.5 (63.6, 80.3) IU; p = 0.01] and resulted in lower mean plasma insulin concentration [186 (171, 260) vs 252 (198, 336) pmol/l; p = 0.002]. Lower plasma insulin was also documented overnight [160 (136, 192) vs 191 (133, 252) pmol/l; p = 0.01, pooled nights]. Ra_total was similar [26.3 (21.9, 28.0) vs 25.4 (21.0, 29.2) µmol/kg/min; p = 0.19] during the two interventions as was Rd [25.8 (21.0, 26.9) vs 25.2 (21.2, 28.8) µmol/kg/min; p = 0.46]. CONCLUSIONS: A 25% reduction in prandial boluses during closed-loop therapy maintains similar glucose control in adolescents with T1D whilst lowering overall plasma insulin levels. It remains unclear whether closed-loop therapy with a 25% reduction in prandial boluses would prevent postprandial hypoglycaemia.
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- 2015
12. Neuroprotection as a therapeutic target in diabetic retinopathy: a basic approach
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Dal Monte, M., primary, Amato, R., additional, Biagioni, M., additional, Cammalleri, M., additional, and Casini, G., additional
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- 2015
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13. Italian pediatric nutrition survey
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Michelangelo Barbaglia, Luigi Marmetucci, Nicoletta Cimadore, Alessandro Monaci, P. Fiore, Sergio Amarri, Elena Brunori, Maddalena Cioni, Carla Russo, Monica Barrani, P. Gandullia, Giovanna Zuin, Giuseppe Parisi, Rita Bellomo Anna, Michele Pinon, Nunzia Miglietti, Francesca Lizzoli, Elisa Mazzoni, Giulia Bardasi, Marisa Zoppo, Giacomo Cagnoli, S. Borodani, L. Forchielli, Monica Tulli, Fina Belli, Michele Salata, Giovanna Verlato, Vittoria Opinto, Roberto Bonaudo, Luisella Angelotti, Giulia Bruni, Elena Uga, Costantino De Giacomo, Antonietta Antonini Monica, Riccardo Guanà, Flavia Urbano, Rosaria Abate, Barbara Santangelo, Chiara Pettinari, Giovanna Fontanella, Patrizia Fusco, L. Lacitignola, Adalberto Brach Del Prever, Gina Ancora, S. Amarri, Laura Lacitignola, Paola Sparano, Marcello Lanari, Stefano Gatti, Francesca Nesi, Valentina De Cosmi, Alessia Frimaire, A Lezo, Francesca Penagini, Carmen Di Scala, Giuseppina Migliore, Roberta Annibali, Grazia Di Leo, Paola Peverelli, Mara Salmaso, Antonella Lezo, Paola Melli, M. Pastore, E. Brunori, Claudia Banzato, M.I. Spagnuolo, Antonella Diamanti, G. Verlato, Angelo Campanozzi, Mariella Pace, Martina Biagioni, Graziano Memmini, Laura Mistura, Sergio Del Vecchio, Annalisa Famiani, Enrico Felici, Germana Casaccia, Graziana Galvagno, Mario Castello, R. Panceri, Paola Accorsi, Martina Fomasi, Francesca Cortinovis, Michela Perrone, Teresa Capriati, Andrea Chiaro, Silvio Ferraris, Nicola Cecchi, Maria Immacolata Spagnuolo, Patrizia Petitti, Cristina Malaventura, Maria Sangerardi, Enrico Gasparrini, Francesco Savino, Luigi Besenzon, Anna Meneghini, Azzurra Guerra, Alessandra Sala, Maria Magistã Anna, Enrico Aidala, Donata Scatã, Gianluigi Palamone, Tiziano Basso, Giuseppe Maggiore, A. Diamanti, Alessandra Mazzocchi, Alessia Morganti, Andreina Stamati Filomena, Paolo Siani, Roberto Panceri, Maria Pastore, Paolo Gandullia, Lezo, A., Diamanti, A., Capriati, T., Gandullia, P., Fiore, P., Lacitignola, L., Gatti, S., Spagnuolo, M. I., Cecchi, N., Verlato, G., Borodani, S., Forchielli, L., Panceri, R., Brunori, E., Pastore, M., Amarri, S., Abate, R., Accorsi, P., Aidala, E., Ancora, G., Angelotti, L., Annibali, R., Antonini Monica, A., Banzato, C., Barbaglia, M., Bardasi, G., Barrani, M., Basso, T., Brach del Prever, A., Belli, F., Bellomo Anna, R., Besenzon, L., Biagioni, M., Bonaudo, R., Bruni, G., Cagnoli, G., Campanozzi, A., Casaccia, G., Castello, M., Chiaro, A., Cimadore, N., Cioni, M., Cortinovis, F., De Cosmi, V., De Giacomo, C., Del Vecchio, S., Di Leo, G., Di Scala, C., Famiani, A., Felici, E., Ferraris, S., Fomasi, M., Fontanella, G., Frimaire, A., Fusco, P., Galvagno, G., Gasparrini, E., Guana, R., Guerra, A., Lanari, M., Lizzoli, F., Maggiore, G., Magista Anna, M., Malaventura, C., Marmetucci, L., Mazzocchi, A., Mazzoni, E., Melli, P., Memmini, G., Meneghini, A., Miglietti, N., Migliore, G., Mistura, L., Monaci, A., Morganti, A., Nesi, F., Opinto, V., Pace, M., Palamone, G., Parisi, G., Penagini, F., Perrone, M., Petitti, P., Pettinari, C., Peverelli, P., Pinon, M., Russo, C., Sala, A., Salata, M., Salmaso, M., Sangerardi, M., Santangelo, B., Savino, F., Scata, D., Siani, P., Sparano, P., Stamati Filomena, A., Tulli, M., Uga, E., Urbano, F., Zoppo, M., Zuin, G., Abate, Rosaria, Accorsi, Paola, Aidala, Enrico, Amarri, Sergio, Ancora, Gina, Angelotti, Luisella, Annibali, Roberta, Antonini Monica, Antonietta, Banzato, Claudia, Barbaglia, Michelangelo, Bardasi, Giulia, Barrani, Monica, Basso, Tiziano, Brach Del Prever, Adalberto, Belli, Fina, Bellomo Anna, Rita, Besenzon, Luigi, Biagioni, Martina, Bonaudo, Roberto, Bruni, Giulia, Brunori, Elena, Cagnoli, Giacomo, Campanozzi, Angelo, Casaccia, Germana, Castello, Mario, Chiaro, Andrea, Cimadore, Nicoletta, Cioni, Maddalena, Cortinovis, Francesca, De Cosmi, Valentina, De Giacomo, Costantino, Del Vecchio, Sergio, Diamanti, Antonella, Di Leo, Grazia, Di Scala, Carmen, Famiani, Annalisa, Felici, Enrico, Ferraris, Silvio, Fomasi, Martina, Fontanella, Giovanna, Frimaire, Alessia, Fusco, Patrizia, Galvagno, Graziana, Gandullia, Paolo, Gasparrini, Enrico, Guanã , Riccardo, Guerra, Azzurra, Lanari, Marcello, Lacitignola, Laura, Lezo, Antonella, Lizzoli, Francesca, Maggiore, Giuseppe, Magistã Anna, Maria, Malaventura, Cristina, Marmetucci, Luigi, Mazzocchi, Alessandra, Mazzoni, Elisa, Melli, Paola, Memmini, Graziano, Meneghini, Anna, Miglietti, Nunzia, Migliore, Giuseppina, Mistura, Laura, Monaci, Alessandro, Morganti, Alessia, Nesi, Francesca, Opinto, Vittoria, Pace, Mariella, Palamone, Gianluigi, Panceri, Roberto, Parisi, Giuseppe, Pastore, Maria, Penagini, Francesca, Perrone, Michela, Petitti, Patrizia, Pettinari, Chiara, Peverelli, Paola, Pinon, Michele, Russo, Carla, Sala, Alessandra, Salata, Michele, Salmaso, Mara, Sangerardi, Maria, Santangelo, Barbara, Savino, Francesco, Scatã , Donata, Siani, Paolo, Spagnuolo, Maria Immacolata, Sparano, Paola, Stamati Filomena, Andreina, Tulli, Monica, Uga, Elena, Urbano, Flavia, Verlato, Giovanna, Zoppo, Marisa, and Zuin, Giovanna
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0301 basic medicine ,Male ,Pediatrics ,Hospitalized patients ,Endocrinology, Diabetes and Metabolism ,Pediatric nutrition ,0302 clinical medicine ,Child Development ,Endocrinology ,Prevalence ,030212 general & internal medicine ,Growth Charts ,Child ,Nutritional support ,Wasting ,Growth Disorders ,Pediatric ,Stunting ,Nutrition and Dietetics ,Nutritional status ,Nutrition Surveys ,Diabetes and Metabolism ,Italy ,Malnutrition ,Child, Preschool ,Female ,medicine.symptom ,medicine.medical_specialty ,Adolescent ,Nutritional Status ,Socio-culturale ,Malnutrition in children ,03 medical and health sciences ,Young Adult ,medicine ,Humans ,030109 nutrition & dietetics ,business.industry ,Infant ,Anthropometry ,medicine.disease ,Parenteral nutrition ,Chronic Disease ,business ,Child, Hospitalized - Abstract
Introduction the prevalence of malnutrition in children and its impact on clinical outcomes is underrecognized by clinicians in Italy as well as worldwide. A novel definition of pediatric malnutrition has been recently proposed by a working group of the Academy of Nutrition and Dietetics and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.), based on the correlation between illness and the use of zscores of anthropometric measurements. Aim to investigate the prevalence of malnutrition and related nutritional support among hospitalized children in Italy, in a nationwide survey performed in a single day (16/4/2015). Methods an open access website (http://nday.biomedia.net) was used to collected data from 73 hospitals and 101 wards in 14 Italian regions (1994 patients). Anonymous information was collected on hospitals' characteristics, patient's anthropometry, admission diagnosis, presence of chronic diseases and use of nutritional support: oral nutritional supplements (ONS), enteral nutrition (EN) or parenteral nutrition (PN). Z-scores of anthropometric measurements, calculated with Epi Info 7.1.5, defined nutritional status: wasting was identified by BMI or Weight-for-Length z-score (
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- 2017
14. A Multicenter Retrospective Survey regarding Diabetic Ketoacidosis Management in Italian Children with Type 1 Diabetes
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F. De Berardinis, Fortunato Lombardo, G. Zanette, R. Cardani, Ivana Rabbone, C. Zecchino, Barbara Predieri, C. Arnaldi, Barbara Piccini, B. Felappi, Riccardo Bonfanti, D. Lo Presti, B. Mainetti, G. Ignaccolo, F. Stamati, Roberto Franceschi, G. Ponzi, M. S. Coccioli, F. Citriniti, C. Ripoli, F. Chiarelli, Valeria Calcaterra, M. Trada, Giovanni Federico, A. Sabbion, D. Cirillo, Enza Mozzillo, C. Salvo, Francesco Prisco, G. Piredda, Alessandro Salvatoni, Maurizio Delvecchio, R. A. Taccardi, Valentino Cherubini, Gianluca Tornese, G. Morganti, Giulio Maltoni, Nicola Minuto, Giovanni Chiari, S. Zonca, M. Bensa, Franco Meschi, V. De Donno, Martina Biagioni, Silvia Savastio, L. Guerraggio, A. Gualtieri, T. Suprani, A. Franzese, M. G. Berioli, D. Iafusco, Francesco Cadario, Andrea Scaramuzza, A. Favia, Luciano Beccaria, Gian Vincenzo Zuccotti, Sonia Toni, Riccardo Schiaffini, F. Cerutti, N. Lazzaro, Lorenzo Iughetti, B. Pasquino, Francesco Fontana, P. Banin, G. Cardinale, A. Marsciani, Anna Paola Frongia, S. Lucchesi, E. Schieven, R. Lera, R. De Marco, F. Cardella, F. Gallo, Vittoria Cauvin, P. Sogno Valin, E. Prandi, L. Tomaselli, Vanna Graziani, M Bruzzese, Lorenzo Lenzi, F. Mammì, Giuseppe d'Annunzio, Ippolita Patrizia Patera, Stefano Zucchini, C. Maffeis, A. Bobbio, A. Gaiero, V. Castaldo, Alfonso Galderisi, Stefano Tumini, P Buono, C. Monciotti, Elvira Piccinno, D. Pardi, Marco Cappa, Renata Lorini, Marco Marigliano, Zucchini, Stefano, Scaramuzza, Andrea E, Bonfanti, Riccardo, Buono, Pietro, Cardella, Francesca, Cauvin, Vittoria, Cherubini, Valentino, Chiari, Giovanni, D'Annunzio, Giuseppe, Frongia, Anna Paola, Iafusco, Dario, Maltoni, Giulio, Patera, Ippolita Patrizia, Toni, Sonia, Tumini, Stefano, Tornese, Gianluca, Rabbone, Ivana, Lera, R., Bobbio, A., Gualtieri, A., Piccinno, E., Zecchino, C., Pasquino, B., Felappi, B., Prandi, E., Gallo, F., Morganti, G., Ripoli, C., Cardinale, G., Ponzi, G., Castaldo, V., Stamati, F., Lo Presti, D., Tomaselli, L., Citriniti, F., Suprani, T., Bensa, M., Graziani, V., De Berardinis, F., Chiarelli, F., De Marco, R., Lazzaro, N., De Donno, V., Banin, P., Piccini, B., Lenzi, L., Mainetti, B., Coccioli, M. S., Minuto, N., Lorini, R., Trada, M., Sogno Valin, P., Beccaria, L., Lucchesi, S., Bruzzese, M., Mammì, F., Cirillo, D., Pardi, D., Taccardi, R. A., Lombardo, F., Zuccotti, G. V., Meschi, F., Iughetti, L., Predieri, B., Franzese, A., Mozzillo, Enza., Prisco, F., Cadario, F., Savastio, S., Piredda, G., Monciotti, C., Galderisi, A., Salvo, C., Calcaterra, V., Berioli, M. G., Federico, G., Favia, A., Zanette, G., Marsciani, A., Schiaffini, R., Cappa, M., Delvecchio, M., Gaiero, A., Ignaccolo, G., Cerutti, F., Fontana, F., Guerraggio, L., Zonca, S., Franceschi, R., Tornese, G., Biagioni, M., Salvatoni, A., Cardani, R., Marigliano, M., Sabbion, A., Maffeis, C., Schieven, E., Arnaldi, C., Zucchini, S., Scaramuzza, A. E., Bonfanti, R., Buono, P., Cardella, F., Cauvin, V., Cherubini, V., Chiari, G., D'Annunzio, G., Frongia, A. P., Iafusco, D., Maltoni, G., Patera, I. P., Toni, S., Tumini, S., Rabbone, I., Mammi, F., Mozzillo, E., and Prisco, Francesco
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0301 basic medicine ,Male ,Pediatrics ,Endocrinology, Diabetes and Metabolism ,Endocrinology ,endocrine system diseases ,type 1 diabetes ,Adolescent ,Child ,Child, Preschool ,Diabetes Mellitus, Type 1 ,Diabetic Ketoacidosis ,Female ,Health Care Surveys ,Humans ,Infant ,Infant, Newborn ,Insulin ,Italy ,Rehydration Solutions ,Retrospective Studies ,Treatment Outcome ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,ketoacidosis ,Retrospective Studie ,Medicine ,Diabetology ,Diabetes and Metabolism ,Newly diagnosed diabetes ,Research Article ,Type 1 ,Human ,medicine.medical_specialty ,Article Subject ,Referral ,Diabetic ketoacidosis ,Diabetic Ketoacidosi ,03 medical and health sciences ,children ,Retrospective survey ,Diabetes mellitus ,Diabetes Mellitus ,Preschool ,Type 1 diabetes ,lcsh:RC648-665 ,business.industry ,Rehydration Solution ,nutritional and metabolic diseases ,Retrospective cohort study ,Newborn ,medicine.disease ,030104 developmental biology ,Health Care Survey ,business - Abstract
We conducted a retrospective survey in pediatric centers belonging to the Italian Society for Pediatric Diabetology and Endocrinology. The following data were collected for all new-onset diabetes patients aged 0–18 years: DKA (pH < 7.30), severe DKA (pH < 7.1), DKA in preschool children, DKA treatment according to ISPAD protocol, type of rehydrating solution used, bicarbonates use, and amount of insulin infused. Records(n=2453)of children with newly diagnosed diabetes were collected from 68/77 centers (87%), 39 of which are tertiary referral centers, the majority of whom (n=1536, 89.4%) were diagnosed in the tertiary referral centers. DKA was observed in 38.5% and severe DKA in 10.3%. Considering preschool children, DKA was observed in 72%, and severe DKA in 16.7%. Cerebral edema following DKA treatment was observed in 5 (0.5%). DKA treatment according to ISPAD guidelines was adopted in 68% of the centers. In the first 2 hours, rehydration was started with normal saline in all centers, but with different amount. Bicarbonate was quite never been used. Insulin was infused starting from third hour at the rate of 0.05–0.1 U/kg/h in 72% of centers. Despite prevention campaign, DKA is still observed in Italian children at onset, with significant variability in DKA treatment, underlying the need to share guidelines among centers.
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- 2016
15. Visual impairment in FOXG1-mutated individuals and mice
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Alessandra Rufa, J. Hayek, M. Biagioni, C. Lo Rizzo, Tommaso Pizzorusso, M. Gennaro, Francesca Mari, Ilaria Meloni, Alessandra Renieri, Mario Costa, Francesca Ariani, L. Pancrazi, Edoardo Novelli, Anna Panighini, E Strettoi, Elena Boggio, Boggio, E. M., Pancrazi, L., Gennaro, Mariangela, Lo Rizzo, C., Mari, F., Meloni, I., Ariani, F., Panighini, A., Novelli, E., Biagioni, M., Strettoi, E., Hayek, J., Rufa, A., Pizzorusso, Tommaso, Renieri, A., and Costa, M.
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0301 basic medicine ,Male ,genetic structures ,Autism ,CDKL5 ,Visual Physiology ,Visual Acuity ,Haploinsufficiency ,Visual system ,Inbred C57BL ,Settore BIO/09 - Fisiologia ,Transgenic ,Cortical blindne ,Cohort Studies ,Mice ,0302 clinical medicine ,Rett syndrome ,Cortical blindness ,Inhibitory interneurons ,Visual cortex ,West syndrome ,Animals ,Child, Preschool ,Disease Models, Animal ,Evoked Potentials, Visual ,Female ,Forkhead Transcription Factors ,Humans ,Infant ,Mice, Inbred C57BL ,Mice, Transgenic ,Mutation ,Nerve Tissue Proteins ,Neurons ,Retina ,Rett Syndrome ,Vision Disorders ,Visual Cortex ,Visual Pathways ,Young Adult ,Neuroscience (all) ,Visual Pathway ,Child ,Evoked Potentials ,General Neuroscience ,FOXG1 ,medicine.anatomical_structure ,Inhibitory interneuron ,Evoked Potential ,Visual ,Human ,Disease Model ,Biology ,MECP2 ,03 medical and health sciences ,medicine ,Preschool ,Animal ,Vision Disorder ,Forkhead Transcription Factor ,Neuron ,medicine.disease ,eye diseases ,030104 developmental biology ,Nerve Tissue Protein ,Disease Models ,Cohort Studie ,Neuroscience ,030217 neurology & neurosurgery - Abstract
The Forkead Box G1 (FOXG1 in humans, Foxg1 in mice) gene encodes for a DNA-binding transcription factor, essential for the development of the telencephalon in mammalian forebrain. Mutations in FOXG1 have been reported to be involved in the onset of Rett Syndrome, for which sequence alterations of MECP2 and CDKL5 are known. While visual alterations are not classical hallmarks of Rett syndrome, an increasing body of evidence shows visual impairment in patients and in MeCP2and CDKL5 animal models. Herein we focused on the functional role of FOXG1 in the visual system of animal models (Foxg1+/Cre mice) and of a cohort of subjects carrying FOXG1 mutations or deletions. Visual physiology of Foxg1+/Cre mice was assessed by visually evoked potentials, which revealed a significant reduction in response amplitude and visual acuity with respect to wild-type littermates. Morphological investigation showed abnormalities in the organization of excitatory/inhibitory circuits in the visual cortex. No alterations were observed in retinal structure. By examining a cohort of FOXG1-mutated individuals with a panel of neuro-ophthalmological assessments, we found that all of them exhibited visual alterations compatible with high-level visual dysfunctions. In conclusion our data show that Foxg1 haploinsufficiency results in an impairment of mouse and human visual cortical function. The Forkead Box G1 (FOXG1 in humans, Foxg1 in mice) gene encodes for a DNA-binding transcription factor, essential for the development of the telencephalon in mammalian forebrain. Mutations in FOXG1 have been reported to be involved in the onset of Rett Syndrome, for which sequence alterations of MECP2 and CDKL5 are known. While visual alterations are not classical hallmarks of Rett syndrome, an increasing body of evidence shows visual impairment in patients and in MeCP2and CDKL5 animal models. Herein we focused on the functional role of FOXG1 in the visual system of animal models (Foxg1(+/Cre) mice) and of a cohort of subjects carrying FOXG1 mutations or deletions. Visual physiology of Foxg1(+/Cre) mice was assessed by visually evoked potentials, which revealed a significant reduction in response amplitude and visual acuity with respect to wild-type littermates. Morphological investigation showed abnormalities in the organization of excitatory/inhibitory circuits in the visual cortex. No alterations were observed in retinal structure. By examining a cohort of FOXG1-mutated individuals with a panel of neuroophthalmological assessments, we found that all of them exhibited visual alterations compatible with high-level visual dysfunctions. In conclusion our data show that Foxg1 haploinsufficiency results in an impairment of mouse and human visual cortical function. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
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- 2016
16. Biologically defined neuronal synuclein disease as a tool to advance drug development.
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Pagano G, Dam T, Kerchner GA, Galpern WR, Biagioni M, Karan R, Jennings D, Peterschmitt MJ, Nikolcheva T, and Brundin P
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Competing Interests: Competing interests: G.P., G.A.K., P.B., and T.N. are employees and shareholders of F. Hoffmann-La Roche Ltd. P.B. also has ownership interests in Acousort AB, Enterin Inc, Axial Therapeutics, and Kenai Therapeutics. T.D. is an employee and shareholder of Neumora Therapeutics. W.R.G. is an employee of Janssen Research & Development, LLC, and holds stock and stock options in Johnson & Johnson. M.B. is an employee of UCB. R.K. is an employee and shareholder of Novartis Pharma AG. D.J. is an employee and shareholder of Denali Therapeutics. M.J.P. is an employee of Sanofi and may hold shares and/or stock options in the company.
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- 2024
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17. Multiscale spatio-temporal dynamics of UBE3A gene in brain physiology and neurodevelopmental disorders.
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Biagioni M, Baronchelli F, and Fossati M
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- Humans, Animals, Chromosomes, Human, Pair 15 genetics, Neurons metabolism, Ubiquitin-Protein Ligases genetics, Ubiquitin-Protein Ligases metabolism, Brain metabolism, Neurodevelopmental Disorders genetics, Angelman Syndrome genetics
- Abstract
The UBE3A gene, located in the chromosomal region 15q11-13, is subject to neuron-specific genomic imprinting and it plays a critical role in brain development. Genetic defects of UBE3A cause severe neurodevelopmental disorders, namely the Angelman syndrome (AS) and the 15q11.2-q13.3 duplication syndrome (Dup15q). In the last two decades, the development of in vitro and in vivo models of AS and Dup15q were fundamental to improve the understanding of UBE3A function in the brain. However, the pathogenic mechanisms of these diseases remain elusive and effective treatments are lacking. Recent evidence suggests that UBE3A functions are both spatially and temporally specific, varying across subcellular compartments, brain regions, and neuronal circuits. In the present review, we summarize current knowledge on the role of UBE3A in neuronal pathophysiology under this spatio-temporal perspective. Additionally, we propose key research questions that will be instrumental to better understand the pathogenic mechanisms underpinning AS and Dup15q disorders and provide the rationale to develop novel therapies., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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18. Art therapy as a comprehensive complementary treatment for Parkinson's disease.
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Ettinger T, Berberian M, Acosta I, Cucca A, Feigin A, Genovese D, Pollen T, Rieders J, Kilachand R, Gomez C, Kaimal G, Biagioni M, Di Rocco A, Ghilardi FM, and Rizzo JR
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Introduction: Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. Complementary and alternative therapies are increasingly utilized to address its complex multisystem symptomatology. Art therapy involves motoric action and visuospatial processing while promoting broad biopsychosocial wellness. The process involves hedonic absorption, which provides an escape from otherwise persistent and cumulative PD symptoms, refreshing internal resources. It involves the expression in nonverbal form of multilayered psychological and somatic phenomena; once these are externalized in a symbolic arts medium, they can be explored, understood, integrated, and reorganized through verbal dialogue, effecting relief and positive change., Methods: 42 participants with mild to moderate PD were treated with 20 sessions of group art therapy. They were assessed before and after therapy with a novel arts-based instrument developed to match the treatment modality for maximum sensitivity. The House-Tree-Person PD Scale (HTP-PDS) assesses motoric and visuospatial processing-core PD symptoms-as well as cognition (thought and logic), affect/mood, motivation, self (including body-image, self-image, and self- efficacy), interpersonal functioning, creativity, and overall level of functioning. It was hypothesized that art therapy will ameliorate core PD symptoms and that this will correlate with improvements in all other variables., Results: HTP-PDS scores across all symptoms and variables improved significantly, though causality among variables was indeterminate., Discussion: Art therapy is a clinically efficacious complementary treatment for PD. Further research is warranted to disentangle causal pathways among the aforementioned variables, and additionally, to isolate and examine the multiple, discrete healing mechanisms believed to operate simultaneously in art therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ettinger, Berberian, Acosta, Cucca, Feigin, Genovese, Pollen, Rieders, Kilachand, Gomez, Kaimal, Biagioni, Di Rocco, Ghilardi and Rizzo.)
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- 2023
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19. Development and early qualitative evidence of two novel patient-reported outcome instruments to assess daily functioning in people with early-stage Parkinson's.
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Morel T, Cleanthous S, Andrejack J, Barker RA, Biagioni M, Blavat G, Bloem BR, Boroojerdi B, Brooks W, Burns P, Cano S, Gallagher C, Gosden L, Siu C, Slagle AF, Ratcliffe N, and Schroeder K
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- Humans, Qualitative Research, Surveys and Questionnaires, Patient Reported Outcome Measures, Research Design, Parkinson Disease diagnosis
- Abstract
Background: Previous research on concepts that are important to people living with early-stage Parkinson's indicated that 'functional' slowness, fine motor skills, and subtle gait abnormalities are cardinal concepts that are not comprehensively captured by existing patient-reported outcome (PRO) instruments that are used in clinical practice and research to assess symptoms and daily functioning within this patient population. We sought to develop novel PRO instruments to address this unmet need., Methods: PRO instrument development was led by a multidisciplinary research group, including people living with Parkinson's (termed 'patient experts'), as well as patient engagement and involvement, regulatory science, clinical, and outcome measurement experts. A first set of PRO instruments, termed Early Parkinson's Function Slowness (42 items) and Early Parkinson's Mobility (26 items), were drafted to capture 'functional' slowness, fine motor skills, and subtle gait abnormalities. These PRO instruments were used in cognitive debriefing interviews with people living with early-stage Parkinson's (who were not involved with the multidisciplinary research group) to identify issues with relevance, clarity, ease of completion, conceptual overlap, or missing concepts., Results: Sixty people living with early-stage Parkinson's were interviewed, which led to refining the items to 45 for the Early Parkinson's Functional Slowness and 23 for the Early Parkinson's Mobility PRO instruments. Refinement included rewording items to address clarity issues, merging or splitting items to address overlap issues, and adding new items to address missing concepts. The Early Parkinson's Function Slowness PRO instrument resulted in a multidimensional instrument covering upper limb, complex/whole body, general activity, and cognitive functional slowness. The Early Parkinson's Mobility PRO instrument resulted in comprehensive coverage of everyday mobility tasks, with a focus on gait concepts, plus complex/whole body, balance, and lower limb mobility., Conclusions: The Early Parkinson's Function Slowness and Early Parkinson's Mobility PRO instruments aim to address gaps in existing PRO instruments to measure meaningful symptoms and daily functioning in people living with early-stage Parkinson's. Utilizing a meticulous study design led by a multidisciplinary research group that included patient experts helped to ensure that the PRO instruments were patient-centric, content valid, and meaningful from a clinical and measurement perspective., (© 2023. The Author(s).)
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- 2023
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20. Retinal Pigment Epithelium Remodeling in Mouse Models of Retinitis Pigmentosa.
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Napoli D, Biagioni M, Billeri F, Di Marco B, Orsini N, Novelli E, and Strettoi E
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- Animals, Dexamethasone pharmacology, Disease Models, Animal, Evaluation Studies as Topic, Inflammation metabolism, Inflammation physiopathology, Mice, Mice, Inbred C57BL, Retina drug effects, Retina metabolism, Retinal Cone Photoreceptor Cells drug effects, Retinal Cone Photoreceptor Cells metabolism, Retinal Pigment Epithelium drug effects, Retinal Pigment Epithelium metabolism, Retinal Rod Photoreceptor Cells drug effects, Retinal Rod Photoreceptor Cells metabolism, Retinal Vessels drug effects, Retinal Vessels metabolism, Retinitis Pigmentosa metabolism, Rhodopsin metabolism, Tight Junctions drug effects, Tight Junctions metabolism, Zonula Occludens-1 Protein metabolism, Retina physiopathology, Retinal Pigment Epithelium physiopathology, Retinitis Pigmentosa physiopathology
- Abstract
In retinitis pigmentosa (RP), one of many possible genetic mutations causes rod degeneration, followed by cone secondary death leading to blindness. Accumulating evidence indicates that rod death triggers multiple, non-cell-autonomous processes, which include oxidative stress and inflammation/immune responses, all contributing to cone demise. Inflammation relies on local microglia and recruitment of immune cells, reaching the retina through breakdowns of the inner blood retinal barrier (iBRB). Leakage in the inner retina vasculature suggests similarly altered outer BRB, formed by junctions between retinal pigment epithelium (RPE) cells, which are crucial for retinal homeostasis, immune response, and privilege. We investigated the RPE structural integrity in three models of RP (rd9, rd10, and Tvrm4 mice) by immunostaining for zonula occludens-1 (ZO-1), an essential regulatory component of tight junctions. Quantitative image analysis demonstrated discontinuities in ZO-1 profiles in all mutants, despite different degrees of photoreceptor loss. ZO-1 interruption zones corresponded to leakage of in vivo administered, fluorescent dextran through the choroid-RPE interface, demonstrating barrier dysfunction. Dexamethasone, administered to rd10 mice for rescuing cones, also rescued RPE structure. Thus, previously undetected, stereotyped abnormalities occur in the RPE of RP mice; pharmacological targeting of inflammation supports a feedback loop leading to simultaneous protection of cones and the RPE.
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- 2021
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21. Intestines of non-uniform stiffness mold the corners of wombat feces.
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Yang PJ, Lee AB, Chan M, Kowalski M, Qiu K, Waid C, Cervantes G, Magondu B, Biagioni M, Vogelnest L, Martin A, Edwards A, Carver S, and Hu DL
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- Animals, Australia, Feces, Fungi, Intestines, Marsupialia
- Abstract
The bare-nosed wombat (Vombatus ursinus) is a fossorial, herbivorous, Australian marsupial, renowned for its cubic feces. However, the ability of the wombat's soft intestine to sculpt flat faces and sharp corners in feces is poorly understood. In this combined experimental and numerical study, we show one mechanism for the formation of corners in a highly damped environment. Wombat dissections show that cubes are formed within the last 17 percent of the intestine. Using histology and tensile testing, we discover that the cross-section of the intestine exhibits regions with a two-fold increase in thickness and a four-fold increase in stiffness, which we hypothesize facilitates the formation of corners by contractions of the intestine. Using a mathematical model, we simulate a series of azimuthal contractions of a damped elastic ring composed of alternating stiff and soft regions. Increased stiffness ratio and higher Reynolds number yield shapes that are more square. The corners arise from faster contraction in the stiff regions and relatively slower movement in the center of the soft regions. These results may have applications in manufacturing, clinical pathology, and digestive health.
- Published
- 2021
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22. Myriocin Effect on Tvrm4 Retina, an Autosomal Dominant Pattern of Retinitis Pigmentosa.
- Author
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Piano I, D'Antongiovanni V, Novelli E, Biagioni M, Dei Cas M, Paroni RC, Ghidoni R, Strettoi E, and Gargini C
- Abstract
Tvrm4 mice, a model of autosomal dominant retinitis pigmentosa (RP), carry a mutation of Rhodopsin gene that can be activated by brief exposure to very intense light. Here, we test the possibility of an anatomical, metabolic, and functional recovery by delivering to degenerating Tvrm4 animals, Myriocin, an inhibitor of ceramide de novo synthesis previously shown to effectively slow down retinal degeneration in rd10 mutants (Strettoi et al., 2010; Piano et al., 2013). Different routes and durations of Myriocin administration were attempted by using either single intravitreal (i.v.) or long-term, repeated intraperitoneal (i.p.) injections. The retinal function of treated and control animals was tested by ERG recordings. Retinas from ERG-recorded animals were studied histologically to reveal the extent of photoreceptor death. A correlation was observed between Myriocin administration, lowering of retinal ceramides, and preservation of ERG responses in i.v. injected cases. Noticeably, the i.p. treatment with Myriocin decreased the extension of the retinal-degenerating area, preserved the ERG response, and correlated with decreased levels of biochemical indicators of retinal oxidative damage. The results obtained in this study confirm the efficacy of Myriocin in slowing down retinal degeneration in genetic models of RP independently of the underlying mutation responsible for the disease, likely targeting ceramide-dependent, downstream pathways. Alleviation of retinal oxidative stress upon Myriocin treatment suggests that this molecule, or yet unidentified metabolites, act on cellular detoxification systems supporting cell survival. Altogether, the pharmacological approach chosen here meets the necessary pre-requisites for translation into human therapy to slow down RP., (Copyright © 2020 Piano, D’Antongiovanni, Novelli, Biagioni, Dei Cas, Paroni, Ghidoni, Strettoi and Gargini.)
- Published
- 2020
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23. Retinal Phenotype in the rd9 Mutant Mouse, a Model of X-Linked RP.
- Author
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Falasconi A, Biagioni M, Novelli E, Piano I, Gargini C, and Strettoi E
- Abstract
Retinal degeneration 9 (rd9) mice carry a mutation in the retina specific "Retinitis Pigmentosa GTPase Regulator (RPGR)" Open Reading Frame (ORF) 15 gene, located on the X chromosome and represent a rare model of X-linked Retinitis Pigmentosa (XLRP), a common and severe form of retinal degeneration (Wright et al., 2010; Tsang and Sharma, 2018). The rd9 RPGR-ORF15 mutation in mice causes lack of the protein in photoreceptors and a slow degeneration of these cells with consequent decrease in Outer Nuclear Layer (ONL) thickness and amplitude of ERG responses, as previously described (Thompson et al., 2012). However, relative rates of rod and cone photoreceptor loss, as well as secondary alterations occurring in neuronal and non-neuronal retinal cell types of rd9 mutants remain to be assessed. Aim of this study is to extend phenotype analysis of the rd9 mouse retina focusing on changes occurring in cells directly interacting with photoreceptors. To this purpose, first we estimated rod and cone survival and its degree of intraretinal variation over time; then, we studied the morphology of horizontal and bipolar cells and of the retinal pigment epithelium (RPE), extending our observations to glial cell reactivity. We found that in rd9 retinas rod (but not cone) death is the main cause of decrease in ONL thickness and that degeneration shows a high degree of intraretinal variation. Rod loss drives remodeling in the outer retina, with sprouting of second-order neurons of the rod-pathway and relative sparing of cone pathway elements. Remarkably, despite cone survival, functional defects can be clearly detected in ERG recordings in both scotopic and photopic conditions. Moderate levels of Muller cells and microglial reactivity are sided by striking attenuation of staining for RPE tight junctions, suggesting altered integrity of the outer Blood Retina Barrier (BRB). Because of many features resembling slowly progressing photoreceptor degeneration paradigms or early stages of more aggressive forms of RP, the rd9 mouse model can be considered a rare and useful tool to investigate retinal changes associated to a process of photoreceptor death sustained throughout life and to reveal disease biomarkers (e.g., BRB alterations) of human XLRP., (Copyright © 2019 Falasconi, Biagioni, Novelli, Piano, Gargini and Strettoi.)
- Published
- 2019
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24. Rescuing cones and daylight vision in retinitis pigmentosa mice.
- Author
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Guadagni V, Biagioni M, Novelli E, Aretini P, Mazzanti CM, and Strettoi E
- Subjects
- Animals, Cell Survival, Cyclic Nucleotide Phosphodiesterases, Type 6 deficiency, Disease Progression, Drug Evaluation, Preclinical, Female, Gene Expression Regulation, Macrophage Activation, Male, Maze Learning, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Retinal Cone Photoreceptor Cells pathology, Retinal Rod Photoreceptor Cells enzymology, Retinal Rod Photoreceptor Cells pathology, Retinitis Pigmentosa genetics, Retinitis Pigmentosa pathology, Transcriptome, Visual Acuity, Anti-Inflammatory Agents therapeutic use, Color Vision physiology, Dexamethasone therapeutic use, Retinal Cone Photoreceptor Cells physiology, Retinitis Pigmentosa drug therapy
- Abstract
Hallmark of retinitis pigmentosa (RP) is the primary, genetic degeneration of rods followed by secondary loss of cones, caused by still elusive biologic mechanisms. We previously shown that exposure of rd10 mutant mice, modeling autosomal recessive RP, to environmental enrichment (EE), with enhanced motor, sensorial and social stimuli, results into a sensible delay of retinal degeneration and vision loss. Searching for effectors of EE-mediated retinal protection, we performed transcriptome analysis of the retina of rd10 enriched and control mice and found that gene expression at the peaks of rod and cone degeneration is characterized by a strong inflammatory/immune response, which is however measurably lower in enrichment conditions. Treating rd10 mice with dexamethasone during the period of maximum photoreceptors death lowered retinal inflammation and caused a preservation of cones and cone-mediated vision. Our findings indicate a link between retinal inflammation and bystander cone degeneration, reinforcing the notion that cone vision in RP can be preserved using anti-inflammatory approaches.-Guadagni, V., Biagioni, M., Novelli, E., Aretini, P., Mazzanti, C. M., Strettoi, E. Rescuing cones and daylight vision in retinitis pigmentosa mice.
- Published
- 2019
- Full Text
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25. Generalizing remotely supervised transcranial direct current stimulation (tDCS): feasibility and benefit in Parkinson's disease.
- Author
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Dobbs B, Pawlak N, Biagioni M, Agarwal S, Shaw M, Pilloni G, Bikson M, Datta A, and Charvet L
- Subjects
- Aged, Feasibility Studies, Female, Humans, Male, Parkinson Disease rehabilitation, Telerehabilitation methods, Transcranial Direct Current Stimulation methods
- Abstract
Background: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has been shown to improve common symptoms of neurological disorders like depressed mood, fatigue, motor deficits and cognitive dysfunction. tDCS requires daily treatment sessions in order to be effective. We developed a remotely supervised tDCS (RS-tDCS) protocol for participants with multiple sclerosis (MS) to increase accessibility of tDCS, reducing clinician, patient, and caregiver burden. The goal of this protocol is to facilitate home use for larger trials with extended treatment periods. In this study we determine the generalizability of RS-tDCS paired with cognitive training (CT) by testing its feasibility in participants with Parkinson's disease (PD)., Methods: Following the methods in our MS protocol development, we enrolled sixteen participants (n = 12 male, n = 4 female; mean age 66 years) with PD to complete ten open-label sessions of RS-tDCS paired with CT (2.0 mA × 20 min) at home under the remote supervision of a trained study technician. Tolerability data were collected before, during, and after each individual session. Baseline and follow-up measures included symptom inventories (fatigue and sleep) and cognitive assessments., Results: RS-tDCS was feasible and tolerable for patients with PD, with at-home access leading to high protocol compliance. Side effects were mostly limited to mild sensations of transient itching and burning under the electrode sites. Similar to prior finding sin MS, we found preliminary efficacy for improvement of fatigue and cognitive processing speed in PD., Conclusions: RS-tDCS paired with CT is feasible for participants with PD to receive at home treatment. Signals of benefit for reduced fatigue and improved cognitive processing speed are consistent across the PD and MS samples. RS-tDCS can be generalized to provide tDCS to a range of patients with neurologic disorders for at-home rehabilitation., Trial Registration: ClinicalTrials.gov Identifier: NCT02746705 . Registered April 21st 2016.
- Published
- 2018
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26. Remotely-supervised transcranial direct current stimulation paired with cognitive training in Parkinson's disease: An open-label study.
- Author
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Agarwal S, Pawlak N, Cucca A, Sharma K, Dobbs B, Shaw M, Charvet L, and Biagioni M
- Subjects
- Adult, Aged, Aged, 80 and over, Cognition, Combined Modality Therapy, Female, Humans, Male, Middle Aged, Prospective Studies, Cognitive Behavioral Therapy, Parkinson Disease therapy, Prefrontal Cortex physiology, Telemedicine methods, Transcranial Direct Current Stimulation methods, Videoconferencing
- Abstract
Background: Transcranial direct current stimulation (tDCS) has been explored as a potential intervention in Parkinson's disease (PD) and recent studies have shown promising results in cognitive, gait and motor function. However, evidence of efficacy is limited due to small size studies, short treatment periods, lack of standardization of methodologies and other study design limitations. Remotely supervised-tDCS (RS-tDCS) allows "at-home" study participation, potentially easing recruitment, compliance and overall feasibility for clinical studies., Objective: Here, we aim to explore preliminary effects of RS-tDCS paired with cognitive training in PD by delivering RS-tDCS neuromodulation at participant's home while still maintaining clinical trial standards., Methods: This was a prospective, open-label study using RS-tDCS paired with cognitive training. Each PD participant completed 10 tDCS sessions (20-min, 1.5-2.0-mA, bi-hemispheric DLPFC montage, left anodal), over a span of two weeks. All tDCS sessions were supervised in real-time through videoconferencing. Outcomes included the Unified Parkinson's Disease Rating Scale (UPDRS) and Grooved Pegboard Test., Results: All RS-tDCS sessions were well tolerated and completed successfully. Total UPDRS and motor UPDRS-III scores decreased significantly. Pegboard completion time improved significantly for the non-dominant hand. There was a strong positive correlation between the time of the sessions, and motor improvements in UPDRS part-III., Conclusion: RS-tDCS paradigm through a 'telemedicine protocol' holds therapeutic potential for motor symptoms in PD while maximizing compliance and ease of recruitment. Conducting afternoon sessions might be more effective than during the morning. Our paradigm may be influential in designing future studies and facilitating larger and longer duration clinical trials., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
27. Dysphagia caused by intramural oesophageal pseudodiverticulosis: An unusual endoscopic finding.
- Author
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Biagioni M, Olmos JI, Antelo P, Waldbaum C, Wonaga A, and Sordá J
- Subjects
- Adult, Alcohol Drinking adverse effects, Candidiasis complications, Diagnosis, Differential, Diverticulum diagnosis, Esophageal Stenosis diagnosis, Esophagitis complications, Esophagitis drug therapy, Female, HIV Infections complications, Humans, Proton Pump Inhibitors therapeutic use, Smoking adverse effects, Deglutition Disorders etiology, Esophageal Stenosis complications, Esophagoscopy
- Published
- 2018
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- View/download PDF
28. Visuospatial exploration and art therapy intervention in patients with Parkinson's disease: an exploratory therapeutic protocol.
- Author
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Cucca A, Acosta I, Berberian M, Lemen AC, Rizzo JR, Ghilardi MF, Quartarone A, Feigin AS, Di Rocco A, and Biagioni MC
- Subjects
- Aged, Aged, 80 and over, Brain diagnostic imaging, Female, Fixation, Ocular physiology, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Prospective Studies, Spatial Navigation physiology, Art Therapy, Neurological Rehabilitation methods, Parkinson Disease rehabilitation
- Abstract
Though abnormalities of visuospatial function occur in Parkinson's disease, the impact of such deficits on functional independence and psychological wellbeing has been historically under- recognized, and effective treatments for this impairment are unknown. These symptoms can be encountered at any stage of the disease, affecting many activities of daily living, and negatively influencing mood, self-efficacy, independence, and overall quality of life. Furthermore, visuospatial dysfunction has been recently linked to gait impairment and falls, symptoms that are known to be poor prognostic factors. Here, we aim to present an original modality of neurorehabilitation designed to address visuospatial dysfunction and related symptoms in Parkinson's disease, known as "Art Therapy". Art creation relies on sophisticated neurologic mechanisms including shape recognition, motion perception, sensory-motor integration, abstraction, and eye-hand coordination. Furthermore, art therapy may enable subjects with disability to understand their emotions and express them through artistic creation and creative thinking, thus promoting self-awareness, relaxation, confidence and self-efficacy. The potential impact of this intervention on visuospatial dysfunction will be assessed by means of combined clinical, behavioral, gait kinematic, neuroimaging and eye tracking analyses. Potential favorable outcomes may drive further trials validating this novel paradigm of neurorehabilitation., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2018
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29. Pattern of retinal morphological and functional decay in a light-inducible, rhodopsin mutant mouse.
- Author
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Gargini C, Novelli E, Piano I, Biagioni M, and Strettoi E
- Subjects
- Animals, Cell Survival radiation effects, Light, Mice, Mutant Proteins genetics, Mutant Proteins metabolism, Retinal Cone Photoreceptor Cells physiology, Retinal Cone Photoreceptor Cells radiation effects, Retinal Rod Photoreceptor Cells physiology, Retinal Rod Photoreceptor Cells radiation effects, Disease Models, Animal, Retina pathology, Retina physiology, Retinitis Pigmentosa pathology, Rhodopsin genetics, Rhodopsin metabolism
- Abstract
Hallmarks of Retinitis Pigmentosa (RP), a family of genetic diseases, are a typical rod-cone-degeneration with initial night blindness and loss of peripheral vision, followed by decreased daylight sight and progressive visual acuity loss up to legal blindness. Great heterogeneity in nature and function of mutated genes, variety of mutations for each of them, variability in phenotypic appearance and transmission modality contribute to make RP a still incurable disease. Translational research relies on appropriate animal models mimicking the genetic and phenotypic diversity of the human pathology. Here, we provide a systematic, morphological and functional analysis of Rho
Tvrm4 /Rho+ rhodopsin mutant mice, originally described in 2010 and portraying several features of common forms of autosomal dominant RP caused by gain-of-function mutations. These mice undergo photoreceptor degeneration only when exposed briefly to strong, white light and allow controlled timing of induction of rod and cone death, which therefore can be elicited in adult animals, as observed in human RP. The option to control severity and retinal extent of the phenotype by regulating intensity and duration of the inducing light opens possibilities to exploit this model for multiple experimental purposes. Altogether, the unique features of this mutant make it an excellent resource for retinal degeneration research.- Published
- 2017
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30. Multifocal repetitive TMS for motor and mood symptoms of Parkinson disease: A randomized trial.
- Author
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Brys M, Fox MD, Agarwal S, Biagioni M, Dacpano G, Kumar P, Pirraglia E, Chen R, Wu A, Fernandez H, Wagle Shukla A, Lou JS, Gray Z, Simon DK, Di Rocco A, and Pascual-Leone A
- Subjects
- Aged, Analysis of Variance, Double-Blind Method, Female, Humans, Male, Middle Aged, Parkinson Disease therapy, Psychiatric Status Rating Scales, Transcranial Magnetic Stimulation methods, Treatment Outcome, Mood Disorders etiology, Mood Disorders therapy, Parkinson Disease complications, Prefrontal Cortex physiology
- Abstract
Objective: To assess whether multifocal, high-frequency repetitive transcranial magnetic stimulation (rTMS) of motor and prefrontal cortex benefits motor and mood symptoms in patients with Parkinson disease (PD)., Methods: Patients with PD and depression were enrolled in this multicenter, double-blind, sham-controlled, parallel-group study of real or realistic (electric) sham rTMS. Patients were randomized to 1 of 4 groups: bilateral M1 ( + sham dorsolateral prefrontal cortex [DLPFC]), DLPFC ( + sham M1), M1 + DLPFC, or double sham. The TMS course consisted of 10 daily sessions of 2,000 stimuli for the left DLPFC and 1,000 stimuli for each M1 (50 × 4-second trains of 40 stimuli at 10 Hz). Patients were evaluated at baseline, at 1 week, and at 1, 3, and 6 months after treatment. Primary endpoints were changes in motor function assessed with the Unified Parkinson's Disease Rating Scale-III and in mood with the Hamilton Depression Rating Scale at 1 month., Results: Of the 160 patients planned for recruitment, 85 were screened, 61 were randomized, and 50 completed all study visits. Real M1 rTMS resulted in greater improvement in motor function than sham at the primary endpoint (p < 0.05). There was no improvement in mood in the DLPFC group compared to the double-sham group, as well as no benefit to combining M1 and DLPFC stimulation for either motor or mood symptoms., Conclusions: In patients with PD with depression, M1 rTMS is an effective treatment of motor symptoms, while mood benefit after 2 weeks of DLPFC rTMS is not better than sham. Targeting both M1 and DLPFC in each rTMS session showed no evidence of synergistic effects., Clinicaltrialsgov Identifier: NCT01080794., Classification of Evidence: This study provides Class I evidence that in patients with PD with depression, M1 rTMS leads to improvement in motor function while DLPFC rTMS does not lead to improvement in depression compared to sham rTMS., (© 2016 American Academy of Neurology.)
- Published
- 2016
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31. VEGF as a Survival Factor in Ex Vivo Models of Early Diabetic Retinopathy.
- Author
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Amato R, Biagioni M, Cammalleri M, Dal Monte M, and Casini G
- Subjects
- Animals, Apoptosis physiology, Blotting, Western, Cell Death physiology, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Glucose pharmacology, Glycation End Products, Advanced, Immunohistochemistry, Mice, Neuroprotective Agents pharmacology, Octreotide pharmacology, Oxidative Stress physiology, Pituitary Adenylate Cyclase-Activating Polypeptide pharmacology, Real-Time Polymerase Chain Reaction, Retina pathology, Retinal Vessels pathology, Diabetic Retinopathy metabolism, Retina metabolism, Vascular Endothelial Growth Factor A metabolism
- Abstract
Purpose: Growing evidence indicates neuroprotection as a therapeutic target in diabetic retinopathy (DR). We tested the hypothesis that VEGF is released and acts as a survival factor in the retina in early DR., Methods: Ex vivo mouse retinal explants were exposed to stressors similar to those characterizing DR, that is, high glucose (HG), oxidative stress (OS), or advanced glycation end-products (AGE). Neuroprotection was provided using octreotide (OCT), a somatostatin analog, and pituitary adenylate cyclase activating peptide (PACAP), two well-documented neuroprotectants. Data were obtained with real-time RT-PCR, Western blot, ELISA, and immunohistochemistry., Results: Apoptosis was induced in the retinal explants by HG, OS, or AGE treatments. At the same time, explants also showed increased VEGF expression and release. The data revealed that VEGF is released shortly after exposure of the explants to stressors and before the level of cell death reaches its maximum. Retinal cell apoptosis was inhibited by OCT and PACAP. At the same time, OCT and PACAP also reduced VEGF expression and release. Vascular endothelial growth factor turned out to be a protective factor for the stressed retinal explants, because inhibiting VEGF with a VEGF trap further increased cell death., Conclusions: These data show that protecting retinal neurons from diabetic stress also reduces VEGF expression and release, while inhibiting VEGF leads to exacerbation of apoptosis. These observations suggest that the retina in early DR releases VEGF as a prosurvival factor. Neuroprotective agents may decrease the need of VEGF production by the retina, therefore limiting the risk, in the long term, of pathologic angiogenesis.
- Published
- 2016
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32. TMS enhances retention of a motor skill in Parkinson's disease.
- Author
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Moisello C, Blanco D, Fontanesi C, Lin J, Biagioni M, Kumar P, Brys M, Loggini A, Marinelli L, Abbruzzese G, Quartarone A, Tononi G, Di Rocco A, and Ghilardi MF
- Subjects
- Aged, Female, Humans, Male, Middle Aged, Motor Skills physiology, Parietal Lobe physiology, Parkinson Disease psychology, Parkinson Disease therapy, Retention, Psychology physiology, Transcranial Magnetic Stimulation
- Abstract
Background: In Parkinson's disease (PD), skill retention is poor, even when acquisition rate is generally preserved. Recent work in normal subjects suggests that 5 Hz-repetitive transcranial magnetic stimulation (5Hz-rTMS) may induce phenomena of long-term potentiation at the cortical level., Objective/hypothesis: We thus verified whether, in PD, 5Hz-rTMS enhances retention of a visuo-motor skill that involves the activity of the right posterior parietal cortex., Methods: A group of patients with PD was tested in two two-day sessions, separated by one week (treatment and placebo sessions). The first day of each session, they learned to adapt their movements to a step-wise 60° visual rotation. Immediately after the task, either real 5Hz-rTMS (treatment) or sham (placebo) stimulation was applied over the right posterior parietal cortex (P6). Retention of this motor skill was tested the following day., Results: In patients with PD, adaptation achieved at the end of training was comparable in the treatment and placebo sessions and was similar to that of a group of age-matched controls. However, retention indices tested on the following day were significantly lower in the placebo compared to the treatment session in which retention indices were restored to the level of the controls. Importantly, reaction and movement time as well as other kinematic measures were the same in the treatment and placebo sessions., Conclusion: These results suggest that rTMS applied after the acquisition of a motor skill over specific areas involved in this process might enhance skill retention in PD., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
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