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14 results on '"Zonca S."'

1. Neural structural abnormalities behind altered brain activation in obesity: evidence from meta-analyses of brain activation and morphometric data

Author

Zapparoli, L, Devoto, F, Giannini, G, Zonca, S, Gallo, F, Paulesu, E, Zapparoli, Laura, Devoto, Francantonio, Giannini, Gianluigi, Zonca, Sara, Gallo, Francesca, Paulesu, Eraldo, Zapparoli, L, Devoto, F, Giannini, G, Zonca, S, Gallo, F, Paulesu, E, Zapparoli, Laura, Devoto, Francantonio, Giannini, Gianluigi, Zonca, Sara, Gallo, Francesca, and Paulesu, Eraldo

Abstract

Obesity represents a risk factor for disability with a major bearing on life expectancy. Neuroimaging techniques are contributing to clarify its neurobiological underpinnings. Here, we explored whether structural brain abnormalities might accompany altered brain activations in obesity. We combined and compared data from brain activation studies for food stimuli and the data reported in structural voxel-based morphometry studies. We found that obese individuals have reduced grey matter density and functional activations in the thalamus and midbrain. A functional connectivity analysis based on these two clusters and its quantitative decoding showed that these regions are part of the reward system functional brain network. Moreover, we found specific grey matter hypo-densities in prefrontal cortex for the obese subjects, regions involved in controlled behaviour. These results support theories of obesity that point to reduced bottom-up reward processes (i.e., the Reward Deficit Theory), but also top-down theories postulating a deficit in cognitive control (i.e., the Inhibitory Control Deficit Theory). The same results also warrant a more systematic exploration of obesity whereby the reward of food and the intentional control over consummatory behaviour is manipulated.

Published
2022

2. Stability Analysis of Polytopic Discontinuous Galerkin Approximations of the Stokes Problem with Applications to Fluid–Structure Interaction Problems

Author

Antonietti, P, Mascotto, L, Verani, M, Zonca, S, Antonietti, Paola F., Mascotto, Lorenzo, Verani, Marco, Zonca, Stefano, Antonietti, P, Mascotto, L, Verani, M, Zonca, S, Antonietti, Paola F., Mascotto, Lorenzo, Verani, Marco, and Zonca, Stefano

Abstract

We present a stability analysis of the Discontinuous Galerkin method on polygonal and polyhedral meshes (PolyDG) for the Stokes problem. In particular, we analyze the discrete inf-sup condition for different choices of the polynomial approximation order of the velocity and pressure approximation spaces. To this aim, we employ a generalized inf-sup condition with a pressure stabilization term. We also prove a priori hp-version error estimates in suitable norms. We numerically check the behaviour of the inf-sup constant and the order of convergence with respect to the mesh configuration, the mesh-size, and the polynomial degree. Finally, as a relevant application of our analysis, we consider the PolyDG approximation for a 2D fluid–structure interaction problem and we numerically explore the stability properties of the method.

Published
2022

3. Continuous Subcutaneous Insulin Infusion in Italy: Third National Survey

Author

Bruttomesso D., Laviola L., Lepore G., Bonfanti R., Bozzetto L., Corsi A., Di Blasi V., Girelli A., Grassi G., Iafusco D., Rabbone I., Schiaffini R., Montani V., Colleluori P., Paciotti V., Alfidi P., Grosso J., Tumini S., Cipriano P., Vitacolonna E., Di Vieste G., Minnucci A., Antenucci D., La Penna G., Taraborrelli M., Macerala B., Citro G., De Morelli G., Gnasso A., Irace C., Citriniti F., Lazzaro N., Bruzzese M., Mammi F., De Berardinis F., Santoro E., Corigliano G., Corigliano M., Parillo M., Schettino M., Fresa R., Annuzzi G., Bassi V., Santinelli C., Buono P., Mozzillo E., De Feo E., Esposito K., Petrizzo M., Foglia A., Gatti A., Gentile S., Guarino G., Zanfardino A., Lambiase C., Vitale A., Zucchini S., Maltoni G., Forlani G., Moscatiello S., Suprani T., Bensa M., Tomasi F., Monesi M., Nizzoli M., Acquati S., Chierici G., Milli B., Iughetti L., Predieri B., Cavani R., Romano S., Manicardi V., Michelini M., Cimicchi M. C., Ugolotti D., Zavaroni I., Dei Cas A., Dall'Aglio E., Papi M., Tardio S. M., Calderini M. C., Riboni S., D'Amato L., Zavaroni D., Gastaldi L., Di Bartolo P., Pellicano F., Cirillo A., Graziani V., Di Secli C., Amarri S., Lasagni A., Marsciani A., Pedini A., Pagliani U., Rossi C., Tortul C., Brunato B., Assaloni R., Zanette G., Livolsi P., Petrucco A., Tercelj K., Manca E., Candido R., Tommasi E., Tornese G., Faleschini E., Tonutti L., Agus S., Zanatta M., Rosolen A., Comici A., Graziano F. M., Misischi I., Pozzilli P., Maurizi A. R., Falasca P., Tuccinardi F., Ricciardi G. P., Di Masa P., Ragonese M., Cipolloni L., Buzzetti R., Moretti C., Leto G., Crino A., Bocchini S., Di Perna P., Giuliano M., Frontoni S., Malandrucco I., Pitocco D., Scalpone R., Toscanella F., Cappa M., Ventura C., Bonato V., De Bernardinis M., Cavallo M. G., Leonetti F., Morano S., Mandosi E., Cicconetti E., Ciampittiello G., Marini M. A., Sabato D., Napoli A., Giraudo F., Toscano V., Massimiani F., Fava D., Gargiulo P., Mecca N., Tubili C., Nardone M. R., Morviducci L., Manca-Bitti M. L., Arcano S., Leotta S., Suraci C., Chiaramonte F., Visalli N., Forte E., Palmacci C., Arnaldi C., Tosini D., Querci F., Trevisan R., Bonfadini S., Prandi E., Felappi B., Locatelli F., Fuso V., Rocca A., Meneghini E., Massafra C., Terni T., Elli P., Ruggeri P., Carrai E., Musacchio N., Lovagnini Scher C. A., Marelli G., Vilei V., Richini D., Inversini C., Franzetti I., Bonacina M., Ciucci A., Sciangula L., Duratorre E., Bonomo M., Bertuzzi F., Chebat E., Muratori M., Scaramuzza A., Zuccotti G. V., Bollati P. M., Colapinto P., Orsi E., Palmieri E., Laurenzi A., Molinari C., Frontino G., Veronelli A., Zecchini B., Bianchi A., Torchio G., Lovati E., Ghilardi G., Dagani R., Carugo D., Berra C., Favacchio G., Fochesato E., Pissarelli A., Bucciarelli L., Bulgheroni M., Guerraggio L., Zonca S., Bossi A. C., Berzi D., Mangone I., Cazzaniga E., Rabini R. A., Boemi M., Faloia E., Boscaro M., Sternari G., Iannilli A., Cherubini V., Busciantella Ricci N., Cartechini M. G., Tesei A. M., Maolo G., Galetta M., Vespasiani G., Tinti G., Manfrini S., Aiello A., Di Vincenzo S., Vitale C., Di Caro P., Lera R., Secco A., Lesina A., Romeo F., Origlia C., Giorda C., Chiambretti A. M., Fornengo R., De Donno V., Gallarotti F., Manti R., Marafetti L., Cadario F., Savastio S., Barbieri P., Massucco P., Ali A., Gottero C., Degiovanni M., Bertaina S., Maghenzani G., Tinti D., Fontana F., Giorgino F., Stefanelli G., Cavallo L., Zecchino C., Piccinno E., Ortolani F., Gallo F., Moramarco F., Marino A., Sparasci G., Mileti G., Lamacchia O., Picca G., Coccioli M. S., Micale F., Serra R., Romano I., Savino T., De Cosmo S., Rauseo A., Delvecchio M., Lapolla R., Braione A. F., Papagno G., Baroni M., Melis M., Cossu E., Songini M., Cambuli V. M., Lo Presti D., Timpanaro T. A., Chiavetta A., Garofalo M. R., Tommaselli L., Tumminia A., Scarpitta A. M., Di Benedetto A., Giunta L., Lombardo F., Salzano G., Cardella F., Roppolo R., Provenzano V., Fleres M., Migliorini S., De Luca A., Leopardi A., Beltrami C., Toni S., Guasti G., Lenzi L., Lamanna C., Mannucci E., Lucchesi S., Dicianni G., Aragona M., Del Prato S., Fattor B., Eisath J., Pasquino B., Reinstadler P., Kaufmann P., Incelli G., Rauch S., Romanelli T., Cauvin V., Franceschi R., Soldani C., Scattoni R., Norgiolini R., Celleno R., Torlone E., Bolli G. B., Lalli C., Scarponi M., Bobbio A., Bechaz M., Pianta A., Marangoni A., Arico C. N., Alagona C., Confortin L., Rossi E., Boscolo Bariga A., Nogara A., Bettio M., Frison V., Guidoni G. L., Fongher C., Contin M. L., Cosma A., Vianello S., Bondesan L., Morea A., Volpi A., Coracina A., Panebianco G., Lombardi S., Costa S., Cipponeri E., Vedovato M., Scotton R., Monciotti C. M., Galderisi A., Dalfra M. G., Lapolla A., Zanon M., Lisato G., Mollo F., Calcaterra F., Miola M., Paccagnella A., Sambataro M., Moro E., Trombetta M., Negri C., Sabbion A., Maffeis C., Strazzabosco M., Mesturino C. A., Mingardi R., Bruttomesso, D., Laviola, L., Lepore, G., Bonfanti, R., Bozzetto, L., Corsi, A., Di Blasi, V., Girelli, A., Grassi, G., Iafusco, D., Rabbone, I., Schiaffini, R., Montani, V., Colleluori, P., Paciotti, V., Alfidi, P., Grosso, J., Tumini, S., Cipriano, P., Vitacolonna, E., Di Vieste, G., Minnucci, A., Antenucci, D., La Penna, G., Taraborrelli, M., Macerala, B., Citro, G., De Morelli, G., Gnasso, A., Irace, C., Citriniti, F., Lazzaro, N., Bruzzese, M., Mammi, F., De Berardinis, F., Santoro, E., Corigliano, G., Corigliano, M., Parillo, M., Schettino, M., Fresa, R., Annuzzi, G., Bassi, V., Santinelli, C., Buono, P., Mozzillo, E., De Feo, E., Esposito, K., Petrizzo, M., Foglia, A., Gatti, A., Gentile, S., Guarino, G., Zanfardino, A., Lambiase, C., Vitale, A., Zucchini, S., Maltoni, G., Forlani, G., Moscatiello, S., Suprani, T., Bensa, M., Tomasi, F., Monesi, M., Nizzoli, M., Acquati, S., Chierici, G., Milli, B., Iughetti, L., Predieri, B., Cavani, R., Romano, S., Manicardi, V., Michelini, M., Cimicchi, M. C., Ugolotti, D., Zavaroni, I., Dei Cas, A., Dall'Aglio, E., Papi, M., Tardio, S. M., Calderini, M. C., Riboni, S., D'Amato, L., Zavaroni, D., Gastaldi, L., Di Bartolo, P., Pellicano, F., Cirillo, A., Graziani, V., Di Secli, C., Amarri, S., Lasagni, A., Marsciani, A., Pedini, A., Pagliani, U., Rossi, C., Tortul, C., Brunato, B., Assaloni, R., Zanette, G., Livolsi, P., Petrucco, A., Tercelj, K., Manca, E., Candido, R., Tommasi, E., Tornese, G., Faleschini, E., Tonutti, L., Agus, S., Zanatta, M., Rosolen, A., Comici, A., Graziano, F. M., Misischi, I., Pozzilli, P., Maurizi, A. R., Falasca, P., Tuccinardi, F., Ricciardi, G. P., Di Masa, P., Ragonese, M., Cipolloni, L., Buzzetti, R., Moretti, C., Leto, G., Crino, A., Bocchini, S., Di Perna, P., Giuliano, M., Frontoni, S., Malandrucco, I., Pitocco, D., Scalpone, R., Toscanella, F., Cappa, M., Ventura, C., Bonato, V., De Bernardinis, M., Cavallo, M. G., Leonetti, F., Morano, S., Mandosi, E., Cicconetti, E., Ciampittiello, G., Marini, M. A., Sabato, D., Napoli, A., Giraudo, F., Toscano, V., Massimiani, F., Fava, D., Gargiulo, P., Mecca, N., Tubili, C., Nardone, M. R., Morviducci, L., Manca-Bitti, M. L., Arcano, S., Leotta, S., Suraci, C., Chiaramonte, F., Visalli, N., Forte, E., Palmacci, C., Arnaldi, C., Tosini, D., Querci, F., Trevisan, R., Bonfadini, S., Prandi, E., Felappi, B., Locatelli, F., Fuso, V., Rocca, A., Meneghini, E., Massafra, C., Terni, T., Elli, P., Ruggeri, P., Carrai, E., Musacchio, N., Lovagnini Scher, C. A., Marelli, G., Vilei, V., Richini, D., Inversini, C., Franzetti, I., Bonacina, M., Ciucci, A., Sciangula, L., Duratorre, E., Bonomo, M., Bertuzzi, F., Chebat, E., Muratori, M., Scaramuzza, A., Zuccotti, G. V., Bollati, P. M., Colapinto, P., Orsi, E., Palmieri, E., Laurenzi, A., Molinari, C., Frontino, G., Veronelli, A., Zecchini, B., Bianchi, A., Torchio, G., Lovati, E., Ghilardi, G., Dagani, R., Carugo, D., Berra, C., Favacchio, G., Fochesato, E., Pissarelli, A., Bucciarelli, L., Bulgheroni, M., Guerraggio, L., Zonca, S., Bossi, A. C., Berzi, D., Mangone, I., Cazzaniga, E., Rabini, R. A., Boemi, M., Faloia, E., Boscaro, M., Sternari, G., Iannilli, A., Cherubini, V., Busciantella Ricci, N., Cartechini, M. G., Tesei, A. M., Maolo, G., Galetta, M., Vespasiani, G., Tinti, G., Manfrini, S., Aiello, A., Di Vincenzo, S., Vitale, C., Di Caro, P., Lera, R., Secco, A., Lesina, A., Romeo, F., Origlia, C., Giorda, C., Chiambretti, A. M., Fornengo, R., De Donno, V., Gallarotti, F., Manti, R., Marafetti, L., Cadario, F., Savastio, S., Barbieri, P., Massucco, P., Ali, A., Gottero, C., Degiovanni, M., Bertaina, S., Maghenzani, G., Tinti, D., Fontana, F., Giorgino, F., Stefanelli, G., Cavallo, L., Zecchino, C., Piccinno, E., Ortolani, F., Gallo, F., Moramarco, F., Marino, A., Sparasci, G., Mileti, G., Lamacchia, O., Picca, G., Coccioli, M. S., Micale, F., Serra, R., Romano, I., Savino, T., De Cosmo, S., Rauseo, A., Delvecchio, M., Lapolla, R., Braione, A. F., Papagno, G., Baroni, M., Melis, M., Cossu, E., Songini, M., Cambuli, V. M., Lo Presti, D., Timpanaro, T. A., Chiavetta, A., Garofalo, M. R., Tommaselli, L., Tumminia, A., Scarpitta, A. M., Di Benedetto, A., Giunta, L., Lombardo, F., Salzano, G., Cardella, F., Roppolo, R., Provenzano, V., Fleres, M., Migliorini, S., De Luca, A., Leopardi, A., Beltrami, C., Toni, S., Guasti, G., Lenzi, L., Lamanna, C., Mannucci, E., Lucchesi, S., Dicianni, G., Aragona, M., Del Prato, S., Fattor, B., Eisath, J., Pasquino, B., Reinstadler, P., Kaufmann, P., Incelli, G., Rauch, S., Romanelli, T., Cauvin, V., Franceschi, R., Soldani, C., Scattoni, R., Norgiolini, R., Celleno, R., Torlone, E., Bolli, G. B., Lalli, C., Scarponi, M., Bobbio, A., Bechaz, M., Pianta, A., Marangoni, A., Arico, C. N., Alagona, C., Confortin, L., Rossi, E., Boscolo Bariga, A., Nogara, A., Bettio, M., Frison, V., Guidoni, G. L., Fongher, C., Contin, M. L., Cosma, A., Vianello, S., Bondesan, L., Morea, A., Volpi, A., Coracina, A., Panebianco, G., Lombardi, S., Costa, S., Cipponeri, E., Vedovato, M., Scotton, R., Monciotti, C. M., Galderisi, A., Dalfra, M. G., Lapolla, A., Zanon, M., Lisato, G., Mollo, F., Calcaterra, F., Miola, M., Paccagnella, A., Sambataro, M., Moro, E., Trombetta, M., Negri, C., Sabbion, A., Maffeis, C., Strazzabosco, M., Mesturino, C. A., Mingardi, R., Bruttomesso, D, Laviola, L, Lepore, G, Bonfanti, R, Bozzetto, L, Corsi, A, Di Blasi, V, Girelli, A, Grassi, G, Iafusco, D, Rabbone, I, Schiaffini, R, Montani, V, Colleluori, P, Paciotti, V, Alfidi, P, Grosso, J, Tumini, S, Cipriano, P, Vitacolonna, E, Di Vieste, G, Minnucci, A, Antenucci, D, La Penna, G, Taraborrelli, M, Macerala, B, Citro, G, De Morelli, G, Gnasso, A, Irace, C, Citriniti, F, Lazzaro, N, Bruzzese, M, Mammi, F, De Berardinis, F, Santoro, E, Corigliano, G, Corigliano, M, Parillo, M, Schettino, M, Fresa, R, Annuzzi, G, Bassi, V, Santinelli, C, Buono, P, Mozzillo, E, De Feo, E, Esposito, K, Petrizzo, M, Foglia, A, Gatti, A, Gentile, S, Guarino, G, Zanfardino, A, Lambiase, C, Vitale, A, Zucchini, S, Maltoni, G, Forlani, G, Moscatiello, S, Suprani, T, Bensa, M, Tomasi, F, Monesi, M, Nizzoli, M, Acquati, S, Chierici, G, Milli, B, Iughetti, L, Predieri, B, Cavani, R, Romano, S, Manicardi, V, Michelini, M, Cimicchi, M, Ugolotti, D, Zavaroni, I, Dei Cas, A, Dall'Aglio, E, Papi, M, Tardio, S, Calderini, M, Riboni, S, D'Amato, L, Zavaroni, D, Gastaldi, L, Di Bartolo, P, Pellicano, F, Cirillo, A, Graziani, V, Di Secli, C, Amarri, S, Lasagni, A, Marsciani, A, Pedini, A, Pagliani, U, Rossi, C, Tortul, C, Brunato, B, Assaloni, R, Zanette, G, Livolsi, P, Petrucco, A, Tercelj, K, Manca, E, Candido, R, Tommasi, E, Tornese, G, Faleschini, E, Tonutti, L, Agus, S, Zanatta, M, Rosolen, A, Comici, A, Graziano, F, Misischi, I, Pozzilli, P, Maurizi, A, Falasca, P, Tuccinardi, F, Ricciardi, G, Di Masa, P, Ragonese, M, Cipolloni, L, Buzzetti, R, Moretti, C, Leto, G, Crino, A, Bocchini, S, Di Perna, P, Giuliano, M, Frontoni, S, Malandrucco, I, Pitocco, D, Scalpone, R, Toscanella, F, Cappa, M, Ventura, C, Bonato, V, De Bernardinis, M, Cavallo, M, Leonetti, F, Morano, S, Mandosi, E, Cicconetti, E, Ciampittiello, G, Marini, M, Sabato, D, Napoli, A, Giraudo, F, Toscano, V, Massimiani, F, Fava, D, Gargiulo, P, Mecca, N, Tubili, C, Nardone, M, Morviducci, L, Manca-Bitti, M, Arcano, S, Leotta, S, Suraci, C, Chiaramonte, F, Visalli, N, Forte, E, Palmacci, C, Arnaldi, C, Tosini, D, Querci, F, Trevisan, R, Bonfadini, S, Prandi, E, Felappi, B, Locatelli, F, Fuso, V, Rocca, A, Meneghini, E, Massafra, C, Terni, T, Elli, P, Ruggeri, P, Carrai, E, Musacchio, N, Lovagnini Scher, C, Marelli, G, Vilei, V, Richini, D, Inversini, C, Franzetti, I, Bonacina, M, Ciucci, A, Sciangula, L, Duratorre, E, Bonomo, M, Bertuzzi, F, Chebat, E, Muratori, M, Scaramuzza, A, Zuccotti, G, Bollati, P, Colapinto, P, Orsi, E, Palmieri, E, Laurenzi, A, Molinari, C, Frontino, G, Veronelli, A, Zecchini, B, Bianchi, A, Torchio, G, Lovati, E, Ghilardi, G, Dagani, R, Carugo, D, Berra, C, Favacchio, G, Fochesato, E, Pissarelli, A, Bucciarelli, L, Bulgheroni, M, Guerraggio, L, Zonca, S, Bossi, A, Berzi, D, Mangone, I, Cazzaniga, E, Rabini, R, Boemi, M, Faloia, E, Boscaro, M, Sternari, G, Iannilli, A, Cherubini, V, Busciantella Ricci, N, Cartechini, M, Tesei, A, Maolo, G, Galetta, M, Vespasiani, G, Tinti, G, Manfrini, S, Aiello, A, Di Vincenzo, S, Vitale, C, Di Caro, P, Lera, R, Secco, A, Lesina, A, Romeo, F, Origlia, C, Giorda, C, Chiambretti, A, Fornengo, R, De Donno, V, Gallarotti, F, Manti, R, Marafetti, L, Cadario, F, Savastio, S, Barbieri, P, Massucco, P, Ali, A, Gottero, C, Degiovanni, M, Bertaina, S, Maghenzani, G, Tinti, D, Fontana, F, Giorgino, F, Stefanelli, G, Cavallo, L, Zecchino, C, Piccinno, E, Ortolani, F, Gallo, F, Moramarco, F, Marino, A, Sparasci, G, Mileti, G, Lamacchia, O, Picca, G, Coccioli, M, Micale, F, Serra, R, Romano, I, Savino, T, De Cosmo, S, Rauseo, A, Delvecchio, M, Lapolla, R, Braione, A, Papagno, G, Baroni, M, Melis, M, Cossu, E, Songini, M, Cambuli, V, Lo Presti, D, Timpanaro, T, Chiavetta, A, Garofalo, M, Tommaselli, L, Tumminia, A, Scarpitta, A, Di Benedetto, A, Giunta, L, Lombardo, F, Salzano, G, Cardella, F, Roppolo, R, Provenzano, V, Fleres, M, Migliorini, S, De Luca, A, Leopardi, A, Beltrami, C, Toni, S, Guasti, G, Lenzi, L, Lamanna, C, Mannucci, E, Lucchesi, S, Dicianni, G, Aragona, M, Del Prato, S, Fattor, B, Eisath, J, Pasquino, B, Reinstadler, P, Kaufmann, P, Incelli, G, Rauch, S, Romanelli, T, Cauvin, V, Franceschi, R, Soldani, C, Scattoni, R, Norgiolini, R, Celleno, R, Torlone, E, Bolli, G, Lalli, C, Scarponi, M, Bobbio, A, Bechaz, M, Pianta, A, Marangoni, A, Arico, C, Alagona, C, Confortin, L, Rossi, E, Boscolo Bariga, A, Nogara, A, Bettio, M, Frison, V, Guidoni, G, Fongher, C, Contin, M, Cosma, A, Vianello, S, Bondesan, L, Morea, A, Volpi, A, Coracina, A, Panebianco, G, Lombardi, S, Costa, S, Cipponeri, E, Vedovato, M, Scotton, R, Monciotti, C, Galderisi, A, Dalfra, M, Lapolla, A, Zanon, M, Lisato, G, Mollo, F, Calcaterra, F, Miola, M, Paccagnella, A, Sambataro, M, Moro, E, Trombetta, M, Negri, C, Sabbion, A, Maffeis, C, Strazzabosco, M, Mesturino, C, Mingardi, R, Bruttomesso, Daniela, Laviola, Luigi, Lepore, Giuseppe, Bonfanti, Riccardo, Bozzetto, Lutgarda, Corsi, Andrea, Di Blasi, Vincenzo, Girelli, Angela, Grassi, Giorgio, Iafusco, Dario, Rabbone, Ivana, Schiaffini, Riccardo, and Tornese, Gianluca

Subjects
Blood Glucose, Male, Pediatrics, Glucose control, IMPACT, Cost-Benefit Analysis, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, CHILDREN, Practice Patterns, Infusions, Subcutaneous, law.invention, Settore MED/13, Endocrinology, Randomized controlled trial, law, Surveys and Questionnaires, Insulin, Practice Patterns, Physicians', Child, Adult, Diabetes Mellitus, Type 1, Female, Guideline Adherence, Health Care Surveys, Humans, Hypoglycemic Agents, Italy, Medical Laboratory Technology, Medicine (all), PUMP THERAPY, Subcutaneous, Diabetes, Diabetes and Metabolism, TERM METABOLIC-CONTROL, Human, Type 1, Infusions, medicine.medical_specialty, Keywords KeyWords Plus:TERM METABOLIC-CONTROL, BOLUS CALCULATOR, PEDIATRIC-PATIENTS, CONTROLLED-TRIAL, CSII, Diabetes mellitus, Diabetes Mellitus, medicine, term metabolic-control, bolus calculator, pump therapy, pediatric-patients, controlled-trial, children, impact CSII, Glucose sensors, Cost-Benefit Analysi, Intensive care medicine, Type 1 diabetes, Physicians', Hypoglycemic Agent, business.industry, medicine.disease, Subcutaneous insulin, Infusions, Subcutaneou, Multicenter study, Health Care Survey, business
Abstract

Background: Continuous subcutaneous insulin infusion (CSII) is increasing worldwide, mostly because of improved technology. The aim of this study was to evaluate the current status of CSII in Italy. Materials and Methods: Physicians from 272 diabetes centers received a questionnaire investigating clinical features, pump technology, and management of patients on CSII. Results: Two hundred seventeen centers (79.8%) joined the study and, by the end of April 2013, gave information about 10,152 patients treated with CSII: 98.2% with type 1 diabetes mellitus, 81.4% adults, 57% female, and 61% with a conventional pump versus 39% with a sensor-augmented pump. CSII advanced functions were used by 68% of patients, and glucose sensors were used 12 days per month on average. Fifty-eight percent of diabetes centers had more than 20 patients on CSII, but there were differences among centers and among regions. The main indication for CSII was poor glucose control. Dropout was mainly due to pump wearability or nonoptimal glycemic control. Twenty-four hour assistance was guaranteed in 81% of centers. A full diabetes team (physician+ nurse + dietician + psychologist) was available in 23% of adult-care diabetes centers and in 53%of pediatric diabetes units. Conclusions: CSII keeps increasing in Italy. More work is needed to ensure uniform treatment strategies throughout the country and to improve pump use.

Published
2015
Full Text
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4. Degenerate tetrahedra removal

Author

Dassi, F, Zonca, S, Formaggia, L, DASSI, FRANCO, Formaggia, L., Dassi, F, Zonca, S, Formaggia, L, DASSI, FRANCO, and Formaggia, L.

Abstract

Standard 3D mesh generation algorithms may produce a low quality tetrahedral mesh, i.e., a mesh where the tetrahedra have very small dihedral angles. In this paper, we propose a series of operations to recover these badly-shaped tetrahedra. In particular, we will focus on the shape of these undesired mesh elements by proposing a novel method to distinguish and classify them. For each of these configurations, we apply a suitable sequence of operations to get a higher mesh quality. Finally, we employ a random algorithm to avoid locks and loops in the procedure. The reliability of the proposed mesh optimization algorithm is numerically proved with several examples.

Published
2016

5. Neural structural abnormalities behind altered brain activation in obesity: Evidence from meta-analyses of brain activation and morphometric data

Author

Zapparoli, Laura, Devoto, Francantonio, Giannini, Gianluigi, Zonca, Sara, Gallo, Francesca, Paulesu, Eraldo, Zapparoli, L, Devoto, F, Giannini, G, Zonca, S, Gallo, F, and Paulesu, E

Subjects
Brain Mapping, Cognitive Neuroscience, fMRI, Brain, Neuroimaging, Magnetic Resonance Imaging, Meta-analysis, Neurology, Reward, Reward system, Humans, Radiology, Nuclear Medicine and imaging, Neurology (clinical), Obesity, VBM
Abstract

Obesity represents a risk factor for disability with a major bearing on life expectancy. Neuroimaging techniques are contributing to clarify its neurobiological underpinnings. Here, we explored whether structural brain abnormalities might accompany altered brain activations in obesity. We combined and compared data from brain activation studies for food stimuli and the data reported in structural voxel-based morphometry studies. We found that obese individuals have reduced grey matter density and functional activations in the thalamus and midbrain. A functional connectivity analysis based on these two clusters and its quantitative decoding showed that these regions are part of the reward system functional brain network. Moreover, we found specific grey matter hypo-densities in prefrontal cortex for the obese subjects, regions involved in controlled behaviour. These results support theories of obesity that point to reduced bottom-up reward processes (i.e., the Reward Deficit Theory), but also top-down theories postulating a deficit in cognitive control (i.e., the Inhibitory Control Deficit Theory). The same results also warrant a more systematic exploration of obesity whereby the reward of food and the intentional control over consummatory behaviour is manipulated.

Published
2022

6. Stability Analysis of Polytopic Discontinuous Galerkin Approximations of the Stokes Problem with Applications to Fluid–Structure Interaction Problems

Author

Paola F. Antonietti, Marco Verani, Stefano Zonca, Lorenzo Mascotto, Antonietti, P, Mascotto, L, Verani, M, and Zonca, S

Subjects
Polynomial, Stability (probability), Theoretical Computer Science, Mathematics::Numerical Analysis, Discontinuous Galerkin method, Polygonal and polyhedral meshes, TheoryofComputation_ANALYSISOFALGORITHMSANDPROBLEMCOMPLEXITY, Fluid–structure interaction, Discontinuous Galerkin, FOS: Mathematics, Applied mathematics, Polygon mesh, Degree of a polynomial, Mathematics - Numerical Analysis, Mathematics, ComputingMethodologies_COMPUTERGRAPHICS, Numerical Analysis, Applied Mathematics, General Engineering, Numerical Analysis (math.NA), Computational Mathematics, Computational Theory and Mathematics, Rate of convergence, Polygonal and polyhedral meshe, Constant (mathematics), Software
Abstract

We present a stability analysis of the Discontinuous Galerkin method on polygonal and polyhedral meshes (PolyDG) for the Stokes problem. In particular, we analyze the discrete inf-sup condition for different choices of the polynomial approximation order of the velocity and pressure approximation spaces. To this aim, we employ a generalized inf-sup condition with a pressure stabilization term. We also prove a priori hp-version error estimates in suitable norms. We numerically check the behaviour of the inf-sup constant and the order of convergence with respect to the mesh configuration, the mesh-size, and the polynomial degree. Finally, as a relevant application of our analysis, we consider the PolyDG approximation for a 2D fluid–structure interaction problem and we numerically explore the stability properties of the method.

Published
2022

7. Degenerate tetrahedra removal

Author

Luca Formaggia, Franco Dassi, Stefano Zonca, Dassi, F, Zonca, S, and Formaggia, L

Subjects
Numerical Analysis, Mathematical optimization, Sequence, Tetrahedral mesh, Applied Mathematics, Mesh quality, 010103 numerical & computational mathematics, T-vertices, Tetrahedral mesh,Mesh quality,Mesh adaptation, Topology, 01 natural sciences, Mathematics::Numerical Analysis, Randomized algorithm, 010101 applied mathematics, Computational Mathematics, Computer Science::Graphics, Mesh generation, Tetrahedron, Polygon mesh, Mesh adaptation, 0101 mathematics, Laplacian smoothing, Focus (optics), ComputingMethodologies_COMPUTERGRAPHICS, Mathematics
Abstract

Standard 3D mesh generation algorithms may produce a low quality tetrahedral mesh, i.e., a mesh where the tetrahedra have very small dihedral angles. In this paper, we propose a series of operations to recover these badly-shaped tetrahedra. In particular, we will focus on the shape of these undesired mesh elements by proposing a novel method to distinguish and classify them. For each of these configurations, we apply a suitable sequence of operations to get a higher mesh quality. Finally, we employ a random algorithm to avoid locks and loops in the procedure. The reliability of the proposed mesh optimization algorithm is numerically proved with several examples.

Published
2016

8. A Multicenter Retrospective Survey regarding Diabetic Ketoacidosis Management in Italian Children with Type 1 Diabetes

Author

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

Subjects
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.

Published
2016

9. Extended finite element method for fluid-structure interaction in wave membrane blood pump.

Author

Martinolli M, Biasetti J, Zonca S, Polverelli L, and Vergara C

Subjects
Finite Element Analysis, Hemodynamics
Abstract

Numerical simulations of cardiac blood pump systems are integral to the optimization of device design, hydraulic performance and hemocompatibility. In wave membrane blood pumps, blood propulsion arises from the wave propagation along an oscillating immersed membrane, which generates small pockets of fluid that are pushed towards the outlet against an adverse pressure gradient. We studied the Fluid-Structure Interaction between the oscillating membrane and the blood flow via three-dimensional simulations using the Extended Finite Element Method (XFEM), an unfitted numerical technique that avoids remeshing by using a fluid fixed mesh. Our three-dimensional numerical simulations in a realistic pump geometry highlighted, for the first time in this field of application, that XFEM is a reliable strategy to handle complex industrial problems. Moreover, they showed the role of the membrane deformation in promoting a blood flow towards the outlet despite an adverse pressure gradient. We also simulated the pump system at different pressure conditions and we validated the numerical results against in-vitro experimental data., (© 2021 John Wiley & Sons Ltd.)

Published
2021
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10. Evaluating Residual Cognition in Advanced Cognitive Impairment: The Residual Cognition Assessment.

Author

Soli A, Savoldelli G, Rota A, Zonca S, Belotti G, and Lazzarini F

Subjects
Cognition, Humans, Neuropsychological Tests, Reproducibility of Results, Cognitive Dysfunction diagnosis, Dementia diagnosis, Dementia psychology
Abstract

Background: In nursing homes, most of the patients with dementia are affected by severe cognitive disorder. Care interventions follow an accurate and recurring multidimensional assessment, including cognitive status. There is still a need to develop new performance-based scales for moderate-to-advanced dementia., Objectives: The development of the Residual Cognition Assessment (RCA) responds to the need to create new scales for global cognitive screening in advanced dementia, with some peculiar features: performance based, brief (<5 m), available without specific training, and suitable for nonverbal patients with minimal distress., Methods: Two raters have administered the RCA and the Severe Impairment Battery-short version (SIB-S) to 84 participants with MMSE = 0. After 2-3 weeks, the same sample has been retested. The RCA has been also administered to 40 participants with MMSE 1-10 for a comparison., Results: The RCA has exhibited excellent values for test-retest reliability (intraclass correlation [ICC] = 0.956) as well as for inter-rater reliability (ICC = 0.997). The concurrent validity analyzes have shown strong correlations between the RCA and the SIB-S with ρ = 0.807 (p < 0.01), and the RCA and the Clinical Dementia Rating (CDR) with ρ = -0.663 (p < 0.01). Moderate correlation has been found between the RCA and the Functional Assessment Staging Scale with ρ = -0.435 (p < 0.01). The instrument has showed high internal reliability, too (total: α = 0.899). The RCA has low floor effect (2%) with respect to the SIB-S (58%) but shows ceiling effect in the MMSE 1-10 sample (50%). The ROC curve analyses demonstrate that the RCA is acceptably able to discriminate between subjects with CDR 4/5 with an AUC of 0.92. Exploratory factor analysis shows 3 factors, defined as three major degrees of cognitive performance in advanced dementia, indeed hierarchically structured in three possible levels of decline., Conclusions: The RCA has showed excellent validity and reliability as well as good sensitivity to identify advanced cognitive impairment in dementia, without floor effect. The RCA seems complementary to the MMSE, so advisable when the latter reaches 0. Administration and scoring are simple, and only few minutes are required to assess the patient. The RCA can discriminate at least 3 different major stages in advanced dementias: severe, profound, and late., (© 2021 S. Karger AG, Basel.)

Published
2021
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11. Tissue transglutaminase (TG2) enables survival of human malignant pleural mesothelioma cells in hypoxia.

Author

Zonca S, Pinton G, Wang Z, Soluri MF, Tavian D, Griffin M, Sblattero D, and Moro L

Subjects
Adaptation, Biological genetics, Biomarkers, Tumor genetics, Cell Line, Tumor, Cell Proliferation genetics, Gene Expression Regulation, Neoplastic, Gene Silencing physiology, Humans, Hypoxia pathology, Lung Neoplasms pathology, Mesothelioma pathology, Mesothelioma, Malignant, Pleural Neoplasms pathology, Protein Glutamine gamma Glutamyltransferase 2, Cell Survival genetics, GTP-Binding Proteins genetics, Hypoxia genetics, Lung Neoplasms genetics, Mesothelioma genetics, Pleural Neoplasms genetics, Transglutaminases genetics
Abstract

Malignant pleural mesothelioma (MPM) is an aggressive tumor linked to environmental/occupational exposure to asbestos, characterized by the presence of significant areas of hypoxia. In this study, we firstly explored the expression and the role of transglutaminase 2 (TG2) in MPM cell adaptation to hypoxia. We demonstrated that cells derived from biphasic MPM express the full-length TG2 variant at higher levels than cells derived from epithelioid MPM and normal mesothelium. We observed a significant induction of TG2 expression and activity when cells from biphasic MPM were grown as a monolayer in chronic hypoxia or packed in spheroids, where the presence of a hypoxic core was demonstrated. We described that the hypoxic induction of TG2 was HIF-2 dependent. Importantly, TGM2-v1 silencing caused a marked and significant reduction of MPM cell viability in hypoxic conditions when compared with normoxia. Notably, a TG2-selective irreversible inhibitor that reacts with the intracellular active form of TG2, but not a non-cell-permeable inhibitor, significantly compromised cell viability in MPM spheroids. Understanding the expression and function of TG2 in the adaptation to the hypoxic environment may provide useful information for novel promising therapeutic options for MPM treatment.

Published
2017
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12. KDM6B histone demethylase is an epigenetic regulator of estrogen receptor β expression in human pleural mesothelioma.

Author

Manente AG, Pinton G, Zonca S, Tavian D, Habib T, Jithesh PV, Fennell D, Nilsson S, and Moro L

Subjects
Basic Helix-Loop-Helix Transcription Factors metabolism, Cell Hypoxia, Cell Line, Tumor, Estrogen Receptor beta metabolism, Histones metabolism, Humans, Jumonji Domain-Containing Histone Demethylases metabolism, Lung Neoplasms metabolism, Mesothelioma metabolism, Mesothelioma, Malignant, Methylation, Protein Processing, Post-Translational, Epigenesis, Genetic, Estrogen Receptor beta genetics, Jumonji Domain-Containing Histone Demethylases genetics, Lung Neoplasms genetics, Mesothelioma genetics
Abstract

Aim: To assess the correlation between KDM6B and estrogen receptor β (ERβ) expression in malignant pleural mesothelioma (MPM)., Materials & Methods: We evaluated gene expression by in silico analysis of microarray data, real-time PCR and western blot in MPM tumors and cell lines., Results & Conclusion: We report a strong positive correlation between the expression of KDM6B and ERβ in MPM tumors and cell lines. We describe that, in hypoxia, the HIF2α-KDM6B axis induces an epithelioid morphology and ERβ expression in biphasic MPM cells with estrogen receptor-negative phenotype. Reduced histone H3K27 tri-methylation confirms KDM6B activity under hypoxic conditions. Importantly, cells treated during reoxygenation with the selective ERβ agonist, KB9520, maintain ERβ expression and the less aggressive phenotype acquired in hypoxia.

Published
2016
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13. SIRT1 at the crossroads of AKT1 and ERβ in malignant pleural mesothelioma cells.

Author

Pinton G, Zonca S, Manente AG, Cavaletto M, Borroni E, Daga A, Jithesh PV, Fennell D, Nilsson S, and Moro L

Subjects
Animals, Apoptosis drug effects, Cell Proliferation drug effects, Estrogen Receptor beta agonists, Estrogens pharmacology, Forkhead Box Protein M1 metabolism, Humans, Lung Neoplasms drug therapy, Lung Neoplasms metabolism, Male, Mesothelioma drug therapy, Mesothelioma metabolism, Mesothelioma, Malignant, Mice, Mice, Nude, Pleural Neoplasms drug therapy, Pleural Neoplasms metabolism, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, Biomarkers, Tumor metabolism, Estrogen Receptor beta metabolism, Lung Neoplasms pathology, Mesothelioma pathology, Pleural Neoplasms pathology, Proto-Oncogene Proteins c-akt metabolism, Sirtuin 1 metabolism
Abstract

In this report, we show that malignant pleural mesothelioma (MPM) patients whose tumors express high levels of AKT1 exhibit a significantly worse prognosis, whereas no significant correlation with AKT3 expression is observed. We provide data that establish a phosphorylation independent role of AKT1 in affecting MPM cell shape and anchorage independent cell growth in vitro and highlight the AKT1 isoform-specific nature of these effects.We describe that AKT1 activity is inhibited by the loss of SIRT1-mediated deacetylation and identify, by mass spectrometry, 11 unique proteins that interact with acetylated AKT1.Our data demonstrate a role of the AKT1/SIRT1/FOXM1 axis in the expression of the tumor suppressor ERβ. We further demonstrate an inhibitory feedback loop by ERβ, activated by the selective agonist KB9520, on this axis both in vitro and in vivo.Our data broaden the current knowledge of ERβ and AKT isoform-specific functions that could be valuable in the design of novel and effective therapeutic strategies for MPM.

Published
2016
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14. Intracellular lactate-mediated induction of estrogen receptor beta (ERβ) in biphasic malignant pleural mesothelioma cells.

Author

Manente AG, Pinton G, Zonca S, Cilli M, Rinaldi M, Daga A, Nilsson S, and Moro L

Subjects
Animals, Antineoplastic Agents, Hormonal pharmacology, Basigin genetics, Basigin metabolism, Cell Line, Tumor, Cell Proliferation, Estrogen Receptor beta agonists, Estrogen Receptor beta genetics, Estrogens pharmacology, Gene Expression Regulation, Neoplastic, Humans, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology, Male, Mesothelioma drug therapy, Mesothelioma genetics, Mesothelioma pathology, Mesothelioma, Malignant, Mice, Nude, Monocarboxylic Acid Transporters genetics, Monocarboxylic Acid Transporters metabolism, Muscle Proteins genetics, Muscle Proteins metabolism, Phenotype, Pleural Neoplasms drug therapy, Pleural Neoplasms genetics, Pleural Neoplasms pathology, Proto-Oncogene Proteins c-akt genetics, Proto-Oncogene Proteins c-akt metabolism, RNA Interference, Spheroids, Cellular, Transfection, Tumor Burden, Up-Regulation, Xenograft Model Antitumor Assays, Estrogen Receptor beta metabolism, Lactic Acid metabolism, Lung Neoplasms metabolism, Mesothelioma metabolism, Pleural Neoplasms metabolism
Abstract

Biphasic malignant pleural mesothelioma (MPM) is the second most common histotype of MPM. It is histologically characterized by the concomitant presence of epithelioid and sarcomatoid features, the latter associated with worse prognosis. In this report we describe that silencing of AKT1 in spindle-shaped biphasic MPM cells promotes the shift toward an epithelioid phenotype. Furthermore, AKT1 silencing resulted in decreased expression of the lactate/H+ symporter MCT4 and its chaperone CD147/Basigin, and in the induction of estrogen receptor β (ERβ) expression. We provide evidence that ERβ expression is induced by increased intracellular lactate concentration. Spheroid culturing and tumor growth of ERβ negative biphasic MPM in nude mice resulted in the induction of ERβ expression and response to the selective agonist KB9520. In both models, the treatment with the ERβ agonist results in reduced cell proliferation, decreased expression of MCT4 and CD147/Basigin and increased acetylation and inactivation of AKT1. Collectively, in response to metabolic changes, ERβ expression is induced and exerts an anti-tumor effect through selective agonist activation. The possibility to reverse the more aggressive biphasic mesothelioma histotype by targeting ERβ with a selective agonist could represent a new effective treatment strategy.

Published
2015
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