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1. Extensive antimicrobial resistance mobilization via multicopy plasmid encapsidation mediated by temperate phages

Author

Natalia Montero, Maite Muniesa, Bosco R. Matamoros, Jose F. Delgado-Blas, Cristina Bernabe-Balas, Bruno Gonzalez-Zorn, Manuel Ares-Arroyo, Irene S Mendez, Emilia F Wedel, Carlos Serna, and Lorena Rodríguez-Rubio

Subjects
Microbiology (medical), Biology, medicine.disease_cause, Bacteris, Marker gene, 03 medical and health sciences, Plasmid, Lysogenic cycle, Drug Resistance, Bacterial, Escherichia coli, medicine, AcademicSubjects/MED00740, Bacteriophages, Pharmacology (medical), Gene, Original Research, 030304 developmental biology, Southern blot, Pharmacology, Genetics, 0303 health sciences, Bacteria, 030306 microbiology, Anti-Bacterial Agents, AcademicSubjects/MED00290, Infectious Diseases, Plasmidis, Mobile genetic elements, AcademicSubjects/MED00230, Low copy number, Plasmids
Abstract

ObjectivesTo investigate the relevance of multicopy plasmids in antimicrobial resistance and assess their mobilization mediated by phage particlesMethodsSeveral databases with complete sequences of plasmids and annotated genes were analysed. The 16S methyltransferase gene armA conferring high-level aminoglycoside resistance was used as a marker in eight different plasmids, from different incompatibility groups, and with differing sizes and plasmid copy numbers. All plasmids were transformed into Escherichia coli bearing one of four different lysogenic phages. Upon induction, encapsidation of armA in phage particles was evaluated using qRT–PCR and Southern blotting.ResultsMulticopy plasmids carry a vast set of emerging clinically important antimicrobial resistance genes. However, 60% of these plasmids do not bear mobility (MOB) genes. When carried on these multicopy plasmids, mobilization of a marker gene armA into phage capsids was up to 10000 times more frequent than when it was encoded by a large plasmid with a low copy number.ConclusionsMulticopy plasmids and phages, two major mobile genetic elements (MGE) in bacteria, represent a novel high-efficiency transmission route of antimicrobial resistance genes that deserves further investigation.

Published
2020
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2. The Italian SurveY on carDiac rEhabilitation - 2008 (ISYDE-2008): a snapshot of current cardiac rehabilitation programmes and provides in Italy Part 2: ISYDE-2008 investigators and directory of italian cardiac rehabilitation centers

Author

Tramarin R., De Feo S., Ambrosetti M., Griffo R., Maslowsky F., Vaghi P., Riccio C., Carlon R., Castello A., Ferratini M., Schweiger C., Chieffo C., Diaco T., Ciglia C., Lapolla A., Pietropaolo F., Furgi G., Martin G., Semprini P., Avallone A., Bertoli D., Belardinelli R., Soffiantino F., Scrutinio D., Maxia P., Coco R., Giustarini C., Anniboletti P., Favretto G., Calisi P., Chiavetta C., Guarracini L., Marcellini G., Iannopollo M., Borrello G., Matta M., Peccerillo N., Boncompagni F., Amici A., Feraco E., Pulitano G., Tripodi E., Capomolla S., Golino P., Parrilli G., Di Patria A., Di Gioia C., Miceli D., Perrotta S., Rubino A., Aulitto V., Riccio G., Codec L., Coruzzi P., Violi E., Nardini M., Urbinati S., Dcruz S., Piepoli M., Fucili A., Cerulli M., Roberto B., Balestra G., Tuniz D., Gori P., Marini R., Morgera T., Di Mario F., Volterrani M., Galati A., Salustri A., Jesi A.P., Lacch A., Loperfido F., Corsiglia L., Pantaleo P., Gigli G., Marchesi D., Febo O., Cobelli F., Malinverni C., Jones N., Anzà C., Frizzelli R., Gei P., Acquistapace F., Carugo S., Malfatto G., Meloni C., Giordano A., Schizzarotto A., Zanettini R., Bosco R., Aglieri S., Caprioli G., Cuocina N., Salvetti S., Savonelli C., Corda G., Meinecke C., Castiglioni, Pierfranco R., Giani P., Robustelli F., Gullace G., Passoni F., Barelli M.V., Richichi I., Rossi A., Politi, Persico M., Alessandrini F., Giannuzzi P., Mazzucco G., Bosimini E., Riva G., Massobrio N., Gondoni L., Aina F., Ingignoli B., Cal M.V., Carpagnano A., Costante A., Villella M., La Rosa C., Sannia L., Barbanto P., Rametta R., Albanese D., Circo A., Raciti R., Scarnato L., Dispensa F., La Spina L., Stuto A., Vasco C., Gibiino S., Gabriele M., Dispensieri C., Carini V., Provvidenza M., Scalzini A., Macchi C., Vannucci M., Iacopetti L., Cordoni M., Gabriele F., Pitscheider W., Bettini R., Girardini D., Mandorla S., Anniboletti F., Patriarchi F., Baroni P.L., Bordin F., Biondi P., Bellotto F., Zanocco A., Ponchia A., Mantovani E., Li Greci E., Celegon L., Baracchi S., Pizzolato G., Peroni L., Apolloni E., Guarniero M., Roncon L., VIGORITO, CARLO, Tramarin, R., De Feo, S., Ambrosetti, M., Griffo, R., Maslowsky, F., Vaghi, P., Riccio, C., Carlon, R., Castello, A., Ferratini, M., Schweiger, C., Chieffo, C., Vigorito, Carlo, Diaco, T., Ciglia, C., Lapolla, A., Pietropaolo, F., Furgi, G., Martin, G., Semprini, P., Avallone, A., Bertoli, D., Belardinelli, R., Soffiantino, F., Scrutinio, D., Maxia, P., Coco, R., Giustarini, C., Anniboletti, P., Favretto, G., Calisi, P., Chiavetta, C., Guarracini, L., Marcellini, G., Iannopollo, M., Borrello, G., Matta, M., Peccerillo, N., Boncompagni, F., Amici, A., Feraco, E., Pulitano, G., Tripodi, E., Capomolla, S., Golino, P., Parrilli, G., Di Patria, A., Di Gioia, C., Miceli, D., Perrotta, S., Rubino, A., Aulitto, V., Riccio, G., Codec, L., Coruzzi, P., Violi, E., Nardini, M., Urbinati, S., Dcruz, S., Piepoli, M., Fucili, A., Cerulli, M., Roberto, B., Balestra, G., Tuniz, D., Gori, P., Marini, R., Morgera, T., Di Mario, F., Volterrani, M., Galati, A., Salustri, A., Jesi, A. P., Lacch, A., Loperfido, F., Corsiglia, L., Pantaleo, P., Gigli, G., Marchesi, D., Febo, O., Cobelli, F., Malinverni, C., Jones, N., Anzà, C., Frizzelli, R., Gei, P., Acquistapace, F., Carugo, S., Malfatto, G., Meloni, C., Giordano, A., Schizzarotto, A., Zanettini, R., Bosco, R., Aglieri, S., Caprioli, G., Cuocina, N., Salvetti, S., Savonelli, C., Corda, G., Meinecke, C., Castiglioni, Pierfranco, R., Giani, P., Robustelli, F., Gullace, G., Passoni, F., Barelli, M. V., Richichi, I., Rossi, A., Politi, Persico, M., Alessandrini, F., Giannuzzi, P., Mazzucco, G., Bosimini, E., Riva, G., Massobrio, N., Gondoni, L., Aina, F., Ingignoli, B., Cal, M. V., Carpagnano, A., Costante, A., Villella, M., La Rosa, C., Sannia, L., Barbanto, P., Rametta, R., Albanese, D., Circo, A., Raciti, R., Scarnato, L., Dispensa, F., La Spina, L., Stuto, A., Vasco, C., Gibiino, S., Gabriele, M., Dispensieri, C., Carini, V., Provvidenza, M., Scalzini, A., Macchi, C., Vannucci, M., Iacopetti, L., Cordoni, M., Gabriele, F., Pitscheider, W., Bettini, R., Girardini, D., Mandorla, S., Anniboletti, F., Patriarchi, F., Baroni, P. L., Bordin, F., Biondi, P., Bellotto, F., Zanocco, A., Ponchia, A., Mantovani, E., Li Greci, E., Celegon, L., Baracchi, S., Pizzolato, G., Peroni, L., Apolloni, E., Guarniero, M., and Roncon, L.

Subjects
Pulmonary and Respiratory Medicine, Studio ISYDE, medicine.medical_specialty, Time Factors, Cardiologia Riabilitativa, medicine.medical_treatment, lcsh:Medicine, Directory, Rehabilitation Centers, Risk profile, medicine, Directories as Topic, Internet, Cardiac Rehabilitation, Rehabilitation, business.industry, Core component, Prevenzione Secondaria, lcsh:R, Health Surveys, Government Programs, Italy, Cardiovascular Diseases, Physical therapy, Snapshot (computer storage), Cardiology and Cardiovascular Medicine, business
Abstract

From January 28th to February 10th, 2008 the Italian Society of Cardiac Rehabilitation and Prevention (GICR) conducted a national web-based survey aimed to provide specific and updated information on organization and core components of cardiac rehabilitation (CR) in Italy, and to describe, both in residential and out-patient settings, indications for CR, clinical characteristics of referred patients, risk profile, performed diagnostic procedures, exercise and educational programme, treatments and arrangements for the follow-up [1, 2]. The ISYDE-2008 is a multicenter, longitudinal, prospective observation study whose design was previously described [1, 2].

Published
2016

3. Dried duckweed and commercial feed promote adequate growth performance of tilapia fingerlings

Author

Flávia de A. Tavares, João Bosco R. Rodrigues, Juan Esquivel, Débora Machado Fracalossi, and Rodrigo Roubach

Subjects
food.ingredient, tilapia, duckweed, Feed conversion ratio, Nile tilapia, lemna, Animal science, food, Dry weight, Tilápias nilóticas, medicine, Fontes alternativas de alimento, lcsh:Science, lcsh:QH301-705.5, General Environmental Science, biology, business.industry, Tilapia, biology.organism_classification, Biotechnology, Oreochromis, lcsh:Biology (General), Water temperature, alternative dietary source, General Earth and Planetary Sciences, %22">Fish , lcsh:Q, Lemnáceas, medicine.symptom, business, Weight gain
Abstract

The present study evaluated Nile tilapia when fed on dried duckweed in combination with commercial feed, aiming at reducing production costs. Three diets, which consisted of commercial feed (40% crude protein),dried duckweed or a combination of commercial feed and dried duckweed were fed to triplicate groups of 20 tilapia (Oreochromis niloticus) fi ngerlings. Fish weighing 3.2 ± 0.94g were stocked in nine 1-m3 net cages and fed twice a day for 50 days. The fi nal average weights of fi ngerlings fed commercial feed (21.67g) and 50% feed + 50% dried duckweed (19.53g) were not different (p

Published
2008

4. Ecology of blaNDM and mcr-1

Author

Bosco R. Matamoros, Jose F. Delgado-Blas, and Bruno Gonzalez-Zorn

Subjects
medicine.medical_specialty, Resistant bacteria, Antibiotic resistance, Multidisciplinary approach, Ecology, Public health, Ecology (disciplines), medicine, MCR-1, Biology
Abstract

Antibiotic resistance is one of the most worrying threats to global public health today. Numerous common infections are becoming harder, and even impossible, to treat due to the loss of effectiveness of these molecules against resistant bacteria. This is a complex scenario involving multiple elements, and must therefore be confronted with a multidisciplinary approach (1).

Published
2017

5. PARENTERAL AND ENTERAL FEEDING IN HOSPITALS IN ITALY - A NATIONAL SURVEY

Author

BRAGA , MARCO, BOZZETTI F, DIONIGI P, RADRIZZANI D, IAPICHINO G, SALIS C, SCROCCARO G, GELIO S, MESSORI A, TOGNONI G, ZANELLO M, FERRARA F, CORTI A, FANCHINI P, VERNERO S, CONGEDO RM, DECICCO M, MORELLI M, CARRATA R, LADDAGA L, LATTARULO M, MARCHESI G, SEQUENZA S, STIVALA B, LANZONE L, SOZZI P, RAITANO A, FIACCHI M, PIERANGELI A, RUSSITO G, CAPORALI C, BITTASI P, SANNA P, SAVONA G, USAI C, ACCOGLI P, SELLI L, PUSCEDDU P, IASIELLO G, FAZIO S, BADOINO C, BURLON N, LOMBARDI M, BERTANA P, BARTAZZI D, PAOLUCCI R, TELLA GC, CALLEGARI R, TOFFOLETTO F, TORREGGIANI L, CAMPO S, MICHELETTI I, LIDESTRI G, ZANIN P, GIULIANO G, CHIOLDI G, PERLASCA F, GRANDE W, PINCELLI D, PACCAGNELLA A, FRANCESCONI R, DOMENICONI D, BERTOTTI G, CAMPI A, VIVARELLI R, DONATI D, SIBILLA C, CERVI R, VANNUCCI A, TONELLI F, BRAVO MT, FUSI D, PAGANI M, DESALVO L, AMALFITANO ME, ZUNINO, VANLIUT MT, PIROLA V, CAMPESTRINI G, AGOSTINI S, GALDIERI MT, SEVERINO A, CASULA C, AGUS G, FRANCESCHINI L, SARNI A, VENDRAME G, FRATTINI F, NARDI L, VALENTE F, RAMBELLI G, RUSCONI A, TADDEI G, BARBUSCIA M, COZZAGLIO L, REGALIA E, GIUDICI D, GIANOTTI L, BACCARI P, DALCIN S, MOLENE V, BIFFI R, GALLITELLI L, BIANCHI G, VECCHI G, VILLA E, BARZAN D, MAZZATO M, PIETROMAGGIORI F, CAMPISI M, PALOZZO A, INZALACO M, RICCI G, CASTELLUCCI MG, MAGGIORE E, SALVADORE C, GRUSOVIN MT, MEZZASALMA N, MASO G, PECORELLI O, FINCO C, SARTORI F, BUFFANO G, IACOVELLI W, FERRI T, ZERMANI R, ROVATI P, CEBRELLI T, PALLAVICINI FB, ALBERTARIO F, BOSCO A, OLIVI P, PAOLINI P, DALCANTO L, MARCONCINI F, LAZZARINI R, MALACRIDA A, AMBOLDI A, BONELLI S, FLORIANELLO F, BORIN F, VAGHI GM, FANELLI FR, MANCINI S, GIUSTI D, NANNI G, SANNELLA F, SGANGA G, FELLEGARA P, MOSCONI F, SIGNORELLI I, ORBAN D, CECCHERINI E, ORSINI A, GIULIANO P, ROSA F, ZANELLA A, CROATTO T, TOFFANIN D, BINOTTO F, MARCATO P, MENARDO G, FAUCCI L, SPOLDI L, MARSETTI M, DICOSMO L, FORNASETTI A, MANETTI A, SALVATORE A, ROSSI C, RINALDI S, DEANGELIS C, AZZOLA M, CONTE F, RIZZO V, BONA, MAZZEGO M, LEGGIERI A, CANINO V, PASTORE V, BOSCO R, DEBERNARDI, DISALVATORE A, DEGRAZIA R, MAZZON D, PAPADIA G, TOIGO G, ISCRA F, NEMEZ M, DROBINZ F, MESGEZ D, TRONCON MG, BACCO A, CATTARUZZI C, CINQUE A, PASQUETTO A, CARTEI G, DIBELLO B, MIANI P, CHIZZOLA A, BALDASSARRE M, BORGA P, BORGATO F, SCATTOLINI C, LAVEGGIO L, FRANCESCHINI F, TURTURO F, PORRETTO V, COATI M, NESI L, CARNER M, ZAMPIERI P, GABRIELLI G, TODESCHINI G, FALCONI, MASSIMO, FRATUCELLO G, DELGROSSI S, CITTERIO R, VILLA C, RIVOLTA A, MINUTO D, ORCALLI F, FERRERA G., Braga, Marco, Bozzetti, F, Dionigi, P, Radrizzani, D, Iapichino, G, Salis, C, Scroccaro, G, Gelio, S, Messori, A, Tognoni, G, Zanello, M, Ferrara, F, Corti, A, Fanchini, P, Vernero, S, Congedo, Rm, Decicco, M, Morelli, M, Carrata, R, Laddaga, L, Lattarulo, M, Marchesi, G, Sequenza, S, Stivala, B, Lanzone, L, Sozzi, P, Raitano, A, Fiacchi, M, Pierangeli, A, Russito, G, Caporali, C, Bittasi, P, Sanna, P, Savona, G, Usai, C, Accogli, P, Selli, L, Pusceddu, P, Iasiello, G, Fazio, S, Badoino, C, Burlon, N, Lombardi, M, Bertana, P, Bartazzi, D, Paolucci, R, Tella, Gc, Callegari, R, Toffoletto, F, Torreggiani, L, Campo, S, Micheletti, I, Lidestri, G, Zanin, P, Giuliano, G, Chioldi, G, Perlasca, F, Grande, W, Pincelli, D, Paccagnella, A, Francesconi, R, Domeniconi, D, Bertotti, G, Campi, A, Vivarelli, R, Donati, D, Sibilla, C, Cervi, R, Vannucci, A, Tonelli, F, Bravo, Mt, Fusi, D, Pagani, M, Desalvo, L, Amalfitano, Me, Zunino, Vanliut, Mt, Pirola, V, Campestrini, G, Agostini, S, Galdieri, Mt, Severino, A, Casula, C, Agus, G, Franceschini, L, Sarni, A, Vendrame, G, Frattini, F, Nardi, L, Valente, F, Rambelli, G, Rusconi, A, Taddei, G, Barbuscia, M, Cozzaglio, L, Regalia, E, Giudici, D, Gianotti, L, Baccari, P, Dalcin, S, Molene, V, Biffi, R, Gallitelli, L, Bianchi, G, Vecchi, G, Villa, E, Barzan, D, Mazzato, M, Pietromaggiori, F, Campisi, M, Palozzo, A, Inzalaco, M, Ricci, G, Castellucci, Mg, Maggiore, E, Salvadore, C, Grusovin, Mt, Mezzasalma, N, Maso, G, Pecorelli, O, Finco, C, Sartori, F, Buffano, G, Iacovelli, W, Ferri, T, Zermani, R, Rovati, P, Cebrelli, T, Pallavicini, Fb, Albertario, F, Bosco, A, Olivi, P, Paolini, P, Dalcanto, L, Marconcini, F, Lazzarini, R, Malacrida, A, Amboldi, A, Bonelli, S, Florianello, F, Borin, F, Vaghi, Gm, Fanelli, Fr, Mancini, S, Giusti, D, Nanni, G, Sannella, F, Sganga, G, Fellegara, P, Mosconi, F, Signorelli, I, Orban, D, Ceccherini, E, Orsini, A, Giuliano, P, Rosa, F, Zanella, A, Croatto, T, Toffanin, D, Binotto, F, Marcato, P, Menardo, G, Faucci, L, Spoldi, L, Marsetti, M, Dicosmo, L, Fornasetti, A, Manetti, A, Salvatore, A, Rossi, C, Rinaldi, S, Deangelis, C, Azzola, M, Conte, F, Rizzo, V, Bona, Mazzego, M, Leggieri, A, Canino, V, Pastore, V, Bosco, R, Debernardi, Disalvatore, A, Degrazia, R, Mazzon, D, Papadia, G, Toigo, G, Iscra, F, Nemez, M, Drobinz, F, Mesgez, D, Troncon, Mg, Bacco, A, Cattaruzzi, C, Cinque, A, Pasquetto, A, Cartei, G, Dibello, B, Miani, P, Chizzola, A, Baldassarre, M, Borga, P, Borgato, F, Scattolini, C, Laveggio, L, Franceschini, F, Turturo, F, Porretto, V, Coati, M, Nesi, L, Carner, M, Zampieri, P, Gabrielli, G, Todeschini, G, Falconi, Massimo, Fratucello, G, Delgrossi, S, Citterio, R, Villa, C, Rivolta, A, Minuto, D, Orcalli, F, Ferrera, G., Braga, M, Congedo, R, Tella, G, Bravo, M, Amalfitano, M, Vanliut, M, Galdieri, M, Castellucci, M, Grusovin, M, Pallavicini, F, Vaghi, G, Fanelli, F, Troncon, M, Falconi, M, and Ferrera, G

Subjects
Pediatrics, medicine.medical_specialty, Nutrition and Dietetics, business.industry, medicine.medical_treatment, Insulin, Abdominal distension, Critical Care and Intensive Care Medicine, Enteral administration, Gastroenterology, Discontinuation, Parenteral nutrition, Internal medicine, Intensive care, Medicine, enteral feeding, medicine.symptom, business, Complication, Central venous catheter
Abstract

A multicentre prospective survey on the use of artificial nutrition (AN) and its complications has been carried out on 1657 hospitalised patients including 7.8% in surgical departments, 7.1% in medical departments and 59.9% in intensive care units. Gastrointestinal diseases and cancer were the most frequent pathologies among patients requiring AN. Parenteral nutrition (PN) alone was employed in 1103 (66.5%) patients. In 267 (16.1%) PN was associated with enteral nutrition (EN). 287 (17.3%) patients were fed by the enteral route alone. The average daily energy intake was 35 kcal/kg for central PN, 26 kcal/kg for peripheral PN and 33 kcal/kg for EN. The mean daily nitrogen intake was 0.19 g/kg for central PN, 0.17 g/kg for peripheral PN and 0.20 g/kg for EN. In 10% of patients PN was electrolyte free and in only 50% all the main electrolytes were added. Trace elements were added in 48% of formulations, mainly as multiple combination. Insulin was added in 61% of PN patients, while albumin was given with PN in 20% of patients. Adverse reactions were observed in 10.9% of PN patients and in 11.5% of EN patients. The most frequent complications occurring in parenterally fed patients were infections of the central venous catheter and metabolic alterations (severe electrolyte abnormalities, liver or renal dysfunction, hypo or persistent hyperglycemia). In enterally fed patients the frequent complications were abdominal distension, cramps and diarrhoea. Adverse reactions were responsible for discontinuation of AN in 2.2% of parenterally supported patients and in 5.7% of enterally fed patients.

Published
1994

6. Global Secondary Prevention Strategies to Limit Event Recurrence After Myocardial Infarction

Author

Giannuzzi P., Temporelli P.L., Marchioli R., Maggioni A.P., Balestroni G., Ceci V., Chieffo C., Gattone M., Griffo R., Schweiger C., Tavazzi L., Urbinati S., Valagussa F., Vanuzzo D., Girardini D., Francesconi G., Vona M., Santoni R., Sarno C., Calisi P., Forzoni M., Boncompagni L., Tabouret G., Canci U., Rosato G., Stanco G., Gullace G., Carbone C., Gavazzi A., Mazzoleni D., Pinelli G., Frizzelli R., Tortelli O., Pantaleoni A., Mantovani E., Pettinati G., Storti G., Riccio C., Scrutinio D., Passantino A., Guiducci D., Zobbi G., Vanaria D., Barbanti P., Carini V., Coco R., Borrello G., Mazza M.L., Chiesa F., Sansoni C., Morbelli E., Rossi L., Ciglia C., Di Giovanni P., Cocchieri M., Dò V., Trudu A., Albonic D., Bendinelli S., Iori E., Balestra G., Giacometti N., Coppetti S., Priori S., Masotti G., Fattirolli F., Meniconi L., Paolucci P., Malinverni C., Quarenghi F., Fontanelli A., Marini R., Mandorla S., Provvidenza M., Giordano A., De Giuli F., Odoguardi L., Barsotti S., Moccetti T., Molteni A., Mauri F., Lecchi G., Bettini R., Bertoldi A., Zanettini R., Centeleghe P., Corallo S., Rainoldi M.L., Ferratini M., Tavanelli M., Leonetti G., Malfatto G., Pascotto P., Zanocco A., Buchberger R., Masaro G., Cobelli F., Sala L., Musca G., Cauteruccio M.A., Giallauria F., Mininni N., Morra P., Castello A., Sarullo F.M., Castelli D., Tramarin R., De Salvo M., Porcellati C., Giovagnoni F., Anniboletti P.F., Calisti M.G., Vergoni W., Iacopetti L., Zelaschi F., D'Cruz S., Lopizzo A., Caiazza M., Gigli G., Pastine J., Pulitanò G., Ruggeri A., Piovaccari G., Semprini P., Zavatteri G., Diaco T., Lumia F., Tamiz A.M., Oliva G., Galati A., Picelli A., Picelli F., Bosco R., Marcellini G., Zanchè E., Martin G., Masutti S., Milani L., Pizzolato G.M., Occhi G., Partesana N., Baldi N., Polimeni G., Furgi G., Nicolino A., Bevilacqua R., Ingignoli B., Massobrio N., Avogliero G., Pedretti R., Vaninetti R., Donnangelo L., Chiatto M., Gori P., Garbin R., RICCARDI, GABRIELE, VIGORITO, CARLO, Giannuzzi, P., Temporelli, P. L., Marchioli, R., Maggioni, A. P., Balestroni, G., Ceci, V., Chieffo, C., Gattone, M., Griffo, R., Schweiger, C., Tavazzi, L., Urbinati, S., Valagussa, F., Vanuzzo, D., Girardini, D., Francesconi, G., Vona, M., Santoni, R., Sarno, C., Calisi, P., Forzoni, M., Boncompagni, L., Tabouret, G., Canci, U., Rosato, G., Stanco, G., Gullace, G., Carbone, C., Gavazzi, A., Mazzoleni, D., Pinelli, G., Frizzelli, R., Tortelli, O., Pantaleoni, A., Mantovani, E., Pettinati, G., Storti, G., Riccio, C., Scrutinio, D., Passantino, A., Guiducci, D., Zobbi, G., Vanaria, D., Barbanti, P., Carini, V., Coco, R., Borrello, G., Mazza, M. L., Chiesa, F., Sansoni, C., Morbelli, E., Rossi, L., Ciglia, C., Di Giovanni, P., Cocchieri, M., Dò, V., Trudu, A., Albonic, D., Bendinelli, S., Iori, E., Balestra, G., Giacometti, N., Coppetti, S., Priori, S., Masotti, G., Fattirolli, F., Meniconi, L., Paolucci, P., Malinverni, C., Quarenghi, F., Fontanelli, A., Marini, R., Mandorla, S., Provvidenza, M., Giordano, A., De Giuli, F., Odoguardi, L., Barsotti, S., Moccetti, T., Molteni, A., Mauri, F., Lecchi, G., Bettini, R., Bertoldi, A., Zanettini, R., Centeleghe, P., Corallo, S., Rainoldi, M. L., Ferratini, M., Tavanelli, M., Leonetti, G., Malfatto, G., Pascotto, P., Zanocco, A., Buchberger, R., Masaro, G., Cobelli, F., Riccardi, Gabriele, Sala, L., Musca, G., Cauteruccio, M. A., Vigorito, Carlo, Giallauria, F., Mininni, N., Morra, P., Castello, A., Sarullo, F. M., Castelli, D., Tramarin, R., De Salvo, M., Porcellati, C., Giovagnoni, F., Anniboletti, P. F., Calisti, M. G., Vergoni, W., Iacopetti, L., Zelaschi, F., D'Cruz, S., Lopizzo, A., Caiazza, M., Gigli, G., Pastine, J., Pulitanò, G., Ruggeri, A., Piovaccari, G., Semprini, P., Zavatteri, G., Diaco, T., Lumia, F., Tamiz, A. M., Oliva, G., Galati, A., Picelli, A., Picelli, F., Bosco, R., Marcellini, G., Zanchè, E., Martin, G., Masutti, S., Milani, L., Pizzolato, G. M., Occhi, G., Partesana, N., Baldi, N., Polimeni, G., Furgi, G., Nicolino, A., Bevilacqua, R., Ingignoli, B., Massobrio, N., Avogliero, G., Pedretti, R., Vaninetti, R., Donnangelo, L., Chiatto, M., Gori, P., and Garbin, R.

Subjects
Male, medicine.medical_specialty, Myocardial Infarction, GOSPEL, Angina Pectoris, law.invention, Angina, Randomized controlled trial, law, Internal medicine, Myocardial Revascularization, Secondary Prevention, Internal Medicine, medicine, Clinical endpoint, Humans, Myocardial infarction, Life Style, Stroke, Heart Failure, Cardiac Rehabilitation, business.industry, Surrogate endpoint, Hazard ratio, Middle Aged, medicine.disease, Heart failure, Physical therapy, Female, business, Stress, Psychological
Abstract

Background Secondary prevention is not adequately implemented after myocardial infarction (MI). We assessed the effect on quality of care and prognosis of a long-term, relatively intensive rehabilitation strategy after MI. Methods We conducted a multicenter, randomized controlled trial in patients following standard post-MI cardiac rehabilitation, comparing a long-term, reinforced, multifactorial educational and behavioral intervention with usual care. A total of 3241 patients with recent MI were randomized to a 3-year multifactorial continued educational and behavioral program (intervention group; n = 1620) or usual care (control group; n = 1621). The combination of cardiovascular (CV) mortality, nonfatal MI, nonfatal stroke, and hospitalization for angina pectoris, heart failure, or urgent revascularization procedure was the primary end point. Other end points were major CV events, major cardiac and cerebrovascular events, lifestyle habits, and drug prescriptions. Results End point events occurred in 556 patients (17.2%). Compared with usual care, the intensive intervention did not decrease the primary end point significantly (16.1% vs 18.2%; hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.74-1.04). However, the intensive intervention decreased several secondary end points: CV mortality plus nonfatal MI and stroke (3.2% vs 4.8%; HR, 0.67; 95% CI, 0.47-0.95), cardiac death plus nonfatal myocardial infarction (2.5% vs 4.0%; HR, 0.64; 95% CI, 0.43-0.94), and nonfatal MI (1.4% vs 2.7%; HR, 0.52; 95% CI, 0.31-0.86). A marked improvement in lifestyle habits (ie, exercise, diet, psychosocial stress, less deterioration of body weight control) and in prescription of drugs for secondary prevention was seen in the intervention group. Conclusion The GOSPEL Study is the first trial to our knowledge to demonstrate that a multifactorial, continued reinforced intervention up to 3 years after rehabilitation following MI is effective in decreasing the risk of several important CV outcomes, particularly nonfatal MI, although the overall effect is small. Trial Registration ClinicalTrials.gov Identifier:NCT00421876

Published
2008

7. Human bone marrow mesenchymal stem cells display anti-cancer activity in SCID mice bearing disseminated non-Hodgkin's lymphoma xenografts

Author

Giorgio Zauli, Elisabetta Melloni, Lorenzo Caruso, Sabrina Ingrao, Sonia Zorzet, Raffaella Bosco, Paola Secchiero, Barbara Zavan, Federica Corallini, Claudio Tripodo, Secchiero, P, Zorzet, S, Tripodo, C, Corallini, F, Melloni, E, Caruso, L, Bosco, R, Ingrao, S, Zavan, B, Zauli G., Secchiero, P., Zorzet, Sonia, Tripodo, C., Corallini, F., Melloni, E., Caruso, L., Bosco, R., Ingrao, S., Zavan, B., and Zauli, G.

Subjects
Pathology, medicine.medical_specialty, Stromal cell, Transplantation, Heterologous, Mice, Nude, lcsh:Medicine, mesenchimal stem cells, Mice, SCID, Mice, immune system diseases, hemic and lymphatic diseases, mesenchymal stem cells, non-Hodgkin's lymphoma, Animals, Humans, Medicine, human lymphoma xenograft, Oncology/Hematological Malignancies, lcsh:Science, SCID Mice, Multidisciplinary, Hematology/Bone Marrow and Stem Cell Transplantation, business.industry, Lymphoma, Non-Hodgkin, Lymphoblast, lcsh:R, Mesenchymal stem cell, Non-Hodgkin's Lymphoma, Mesenchymal Stem Cells, Hematopoietic Stem Cells, medicine.disease, Coculture Techniques, Lymphoma, Non-Hodgkin's lymphoma, Endothelial stem cell, Transplantation, Apoptosis, lcsh:Q, Hematology/Lymphomas and Chronic Lymphoblastic Leukemia, business, Research Article
Abstract

Background Although multimodality treatment can induce high rate of remission in many subtypes of non-Hodgkin's lymphoma (NHL), significant proportions of patients relapse with incurable disease. The effect of human bone marrow (BM) mesenchymal stem cells (MSC) on tumor cell growth is controversial, and no specific information is available on the effect of BM-MSC on NHL. Methodology/Principal Findings The effect of BM-MSC was analyzed in two in vivo models of disseminated non-Hodgkin's lymphomas with an indolent (EBV− Burkitt-type BJAB, median survival = 46 days) and an aggressive (EBV+ B lymphoblastoid SKW6.4, median survival = 27 days) behavior in nude-SCID mice. Intra-peritoneal (i.p.) injection of MSC (4 days after i.p. injection of lymphoma cells) significantly increased the overall survival at an optimal MSC∶lymphoma ratio of 1∶10 in both xenograft models (BJAB+MSC, median survival = 58.5 days; SKW6.4+MSC, median survival = 40 days). Upon MSC injection, i.p. tumor masses developed more slowly and, at the histopathological observation, exhibited a massive stromal infiltration coupled to extensive intra-tumor necrosis. In in vitro experiments, we found that: i) MSC/lymphoma co-cultures modestly affected lymphoma cell survival and were characterized by increased release of pro-angiogenic cytokines with respect to the MSC, or lymphoma, cultures; ii) MSC induce the migration of endothelial cells in transwell assays, but promoted endothelial cell apoptosis in direct MSC/endothelial cell co-cultures. Conclusions/Significance Our data demonstrate that BM-MSC exhibit anti-lymphoma activity in two distinct xenograft SCID mouse models of disseminated NHL.

Published
2010

8. Changes in T-Cell Responses Against Human Herpesvirus-8 Correlate with the Disease Course of Iatrogenic Kaposi's Sarcoma in a Patient with Undifferentiated Arthritis

Author

Francesco Volzone, Monica Morselli, Clodoveo Ferri, Leonardo Potenza, Fabio Ciceri, Fabio Forghieri, Patrizia Barozzi, Giovanni Riva, Mario Luppi, Chiara Bonini, Claudio Bordignon, Giulio Rossi, Denise Whitby, Raffaella Bosco, Thomas F. Schulz, Chiara Quadrelli, Daniela Vallerini, Giuseppe Torelli, Barozzi, P, Potenza, L, Riva, G, Vallerini, D, Quadrelli, C, Bosco, R, Morselli, M, Forghieri, F, Volzone, F, Rossi, G, Ferri, C, Bonini, MARIA CHIARA, Ciceri, Fabio, Bordignon, Claudio, Whitby, D, Schulz, Tf, Torelli, G, and Luppi, M.

Subjects
medicine.medical_specialty, T-Lymphocytes, viruses, medicine.medical_treatment, Iatrogenic Disease, Arthritis, Opportunistic Infections, Antibodies, Viral, medicine.disease_cause, Herpesviridae, Immune system, Rheumatology, Internal medicine, medicine, Humans, Sarcoma, Kaposi, Kaposi's sarcoma, HHV-8, immunosuppression, business.industry, ELISPOT, Kaposi sarcoma, virus diseases, Immunosuppression, Middle Aged, Viral Load, medicine.disease, Anesthesiology and Pain Medicine, Herpesvirus 8, Human, Immunology, Disease Progression, undifferentiated arthritis, Female, business, Viral load, Immunosuppressive Agents, Follow-Up Studies
Abstract

Objectives: To describe the first in-depth analysis of both the T-cell responses against human herpesvirus-8 (HHV-8) and the HHV-8 viral load in 1 patient who developed iatrogenic HHV-8-associated-Kaposi's sarcoma (KS) following immunosuppressive treatment for undifferentiated arthritis and to review the literature on iatrogenic KS (IKS). Methods: T-cell responses against HHV-8 lytic and latent antigens were analyzed by ex vivo enzyme-linked immunospot (Elispot) and HHV-8 viral load was assessed by quantitative polymerase chain reaction, in sequential peripheral blood samples from a 55-year-old woman who developed skin/mucosal and visceral KS, while receiving treatment with cyclosporine, methotrexate, and methylprednisolone for undifferentiated arthritis. Results: KS may result from HHV-8 infection in patients undergoing immunosuppressive treatment for rheumatic diseases and this is the first case of IKS occurring in undifferentiated arthritis. A role for immune surveillance in the pathogenesis of IKS is supported by the observation of disease regression following discontinuation of immunosuppressive therapy. In a 4-year follow-up, we showed that variations of the virus-specific immune responses but not of the viral load correlated well with the disease course, characterized by 2 remission and subsequent relapse phases, following changes of immunosuppressive therapy. Conclusions: We have provided evidence of a clear-cut correlation between changes in immunologic markers of HHV-8 infection and the disease course of this viral associated tumor, concomitant with variations of immunosuppressive treatment. Thus, ex vivo enzyme-linked immunospot for HHV-8-specific T-cell responses represents a new tool for the clinical management of rheumatic patients with IKS. (C) 2009 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 39:170-175 RI Rossi, Giulio/C-5576-2011

Published
2009

9. Anti-leukemic activity of dasatinib in both p53(wild-type) and p53(mutated) B malignant cells

Author

Silvano Capitani, Claudio Celeghini, Rebecca Voltan, Marco Rabusin, Federica Corallini, Raffaella Bosco, Paola Secchiero, Bosco, R., Rabusin, M., Voltan, R., Celeghini, Claudio, Corallini, F., Capitani, S., and Secchiero, P.

Subjects
MAPK/ERK pathway, p53, STAT3 Transcription Factor, Time Factors, Cell Survival, p38 mitogen-activated protein kinases, Dasatinib, Antineoplastic Agents, Apoptosis, Leukemic cells, p38 Mitogen-Activated Protein Kinases, hemic and lymphatic diseases, Cell Line, Tumor, medicine, Humans, Pharmacology (medical), Granulocyte Precursor Cells, Phosphorylation, STAT3, Protein Kinase Inhibitors, Pharmacology, Mitogen-Activated Protein Kinase 1, B-Lymphocytes, Mitogen-Activated Protein Kinase 3, biology, Leukemia, Prolymphocytic, B-Cell, Kinase, Chemistry, Wild type, leukemic cell, Cell cycle, G1 Phase Cell Cycle Checkpoints, Thiazoles, Pyrimidines, Oncology, Mutation, biology.protein, Cancer research, Tumor Suppressor Protein p53, medicine.drug
Abstract

The multi-kinase inhibitor Dasatinib induced a variable but significant decrease of viability in both p53(wild-type) (EHEB, JVM-2, JVM-3) and p53(mutated) (MEC-1, MEC-2, BJAB) prolymphocytic B leukemic cells, due to a combination of cell cycle block in G1 and apoptosis. Antibody phospho-kinase array analysis revealed that Dasatinib inhibited the phosphorylation of various kinases, including ERK1/2 and p38/MAPK as well as of STAT3 transcription factors, in both p53(wild-type) and p53(mutated) cells. Therefore, Dasatinib might offer a novel therapeutic strategy not only for p53(wild-type), but also for p53(mutated) B malignancies that have the worst prognosis and urgently need innovative therapeutic approaches.

Published
2010

10. Recent advances in the therapeutic perspectives of nutlin-3

Author

Paola Secchiero, Giorgio Zauli, Claudio Celeghini, Raffaella Bosco, Secchiero, P., Bosco, R., Celeghini, Claudio, and Zauli, G.

Subjects
Cell cycle checkpoint, senescence, synergistic, pediatric malignancies, Pharmacology, chemotherapy, Piperazines, chemistry.chemical_compound, Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Drug Discovery, Cytotoxic T cell, Pediatric malignancies, hematological malignancies, p53 pathway, apoptosis, therapeutic combinations, Nutlin-3, MDM2, HDM2, PEDIATRIC TUMORS, malignancies, P-gp, p53-independent, leukemia, endothelial, autophagic, pharmacokinetics, biology, Retinoblastoma, Imidazoles, Drug Synergism, Proto-Oncogene Proteins c-mdm2, Nutlin, Small molecule, Mdm2, Cell type, Antineoplastic Agents, medicine, Humans, business.industry, Genes, p53, medicine.disease, chemistry, Apoptosis, biology.protein, Cancer research, Tumor Suppressor Protein p53, business, pediatric malignancies, hematological malignancies, p53 pathway, apoptosis, senescence, therapeutic combinations
Abstract

Nutlin-3 is a small molecule inhibitor of the MDM2/p53 interaction, which leads to the non-genotoxic p53 stabilization, activation of cell cycle arrest and apoptosis pathways. A series of recent studies have strengthened the concept that selective, non-genotoxic p53 activation by Nutlin-3 might represent an alternative to the current cytotoxic chemotherapy, in particular for pediatric tumors and for hematological malignancies, which retain a high percentage of p53(wild-type) status at diagnosis. Like most other drugs employed in cancer therapy, it will be unlikely that Nutlin-3 will be used as a monotherapy. In this respect, Nutlin-3 shows a synergistic cytotoxic effect when used in combination with innovative drugs, such as TRAIL or bortozemib. Although Nutlin-3 is currently in phase I clinical trial for the treatment of retinoblastoma, its effects on normal tissues and cell types remain largely to be determined and will require further investigation in the future years.

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