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2. Rationale and design of the CV-PREVITAL study: an Italian multiple cohort randomised controlled trial investigating innovative digital strategies in primary cardiovascular prevention

Author

Baldassarre, D, Iacoviello, L, Baetta, R, Roncaglioni, M, Condorelli, G, Remuzzi, G, Gensini, G, Frati, L, Ricciardi, W, Conaldi, P, Uccelli, A, Blandini, F, Bosari, S, Scambia, G, Fini, M, Di Malta, A, Amato, M, Veglia, F, Bonomi, A, Klersy, C, Colazzo, F, Pengo, M, Gorini, F, Auteri, L, Ferrante, G, Baviera, M, Ambrosio, G, Catapano, A, Gialluisi, A, Malavazos, A, Castelvecchio, S, Corsi-Romanelli, M, Cardani, R, La Rovere, M, Agnese, V, Pane, B, Prati, D, Spinardi, L, Liuzzo, G, Arbustini, E, Volterrani, M, Visconti, M, Werba, J, Genovese, S, Bilo, G, Invitti, C, Di Blasio, A, Lombardi, C, Faini, A, Rosa, D, Ojeda-Fernandez, L, Foresta, A, De Curtis, A, Di Castelnuovo, A, Scalvini, S, Pierobon, A, Gorini, A, Valenti, L, Luzi, L, Racca, A, Bandi, M, Tremoli, E, Menicanti, L, Parati, G, Pompilio, G, Colombo, G, Vavassori, C, Biondi, M, Frigerio, B, Ravani, A, Sansaro, D, Coggi, D, Romandini, A, Giroli, M, Giuliani, M, Bonmi, A, Rondinelli, M, Trudu, C, Cinieri, C, Monturano, M, Colazo, F, Inviti, C, Di Blasi, A, Torlasco, C, Gilardini, L, Soranna, D, Zambon, A, Perger, E, Zanotti, L, Badano, L, Cova, L, Gentilini, D, Grappiolo, L, Condoreli, G, Ferante, G, Papa, L, Savevski, V, Ieva, F, Romano, I, Remzzi, G, Ojeda, L, Clerici, F, Palumbo, A, Genini, G, Catpano, A, Mattioli, R, Longhi, E, Mantovani, L, Madotto, F, Bonaccio, M, Gianfagna, F, Ghulam, A, Magnacca, S, Noro, F, Costanzo, S, Esposito, S, Orlandi, S, Persichillo, M, Bracone, F, Panzera, T, Ruggiero, E, Parisi, R, Franciosa, S, Morelli, M, De Rita, F, Cerletti, C, de Gaetano, G, Donati, M, Mencanti, L, Romanelli, M, Cerri, A, Dubini, C, Trevisan, M, Renna, L, Milani, V, Boveri, S, Giubbilini, P, Ramputi, L, Baroni, I, De Angeli, G, Riciardi, W, Olmetti, F, Bussotti, M, Gaetano, C, Baiardi, P, Bachetti, T, Balbi, M, Comini, L, Lorenzoni, M, Olivares, A, Traversi, E, Garre, C, Sideri, R, Clemenza, F, Gentile, G, Caruana, G, Cuscino, N, Di Gesaro, G, Greco, A, Loddo, I, Tuzzolino, F, Ucelli, A, Palombo, D, Spinella, G, Mozzetta, G, Ameri, P, Zoppoli, G, Finotello, A, Porto, I, Pratesi, G, Bladini, F, Spnardi, L, Clerici, M, Pelusi, S, Bianco, C, Carpani, R, Periti, G, Margarita, S, Lanza, G, Severino, A, Pedicino, D, D'Amario, D, D'Aiello, A, Vinci, R, Bonanni, A, Brecciaroli, M, Filomia, S, Pastorino, R, Boccia, S, Urbani, A, Sanguinetti, M, Santoliquido, A, Proto, L, Tarquini, D, Grimaldi, M, Leonardi, S, Elia, A, Currao, A, Urtis, M, Di Toro, A, Giuliani, L, Caminiti, G, Marcolongo, F, Sposato, B, Guadagni, F, Morsella, V, Marziale, A, Protti, G, Baldassarre D., Iacoviello L., Baetta R., Roncaglioni M. C., Condorelli G., Remuzzi G., Gensini G., Frati L., Ricciardi W., Conaldi P. G., Uccelli A., Blandini F., Bosari S., Scambia G., Fini M., Di Malta A., Amato M., Veglia F., Bonomi A., Klersy C., Colazzo F., Pengo M., Gorini F., Auteri L., Ferrante G., Baviera M., Ambrosio G., Catapano A., Gialluisi A., Malavazos A. E., Castelvecchio S., Corsi-Romanelli M. M., Cardani R., La Rovere M. T., Agnese V., Pane B., Prati D., Spinardi L., Liuzzo G., Arbustini E., Volterrani M., Visconti M., Werba J. P., Genovese S., Bilo G., Invitti C., Di Blasio A., Lombardi C., Faini A., Rosa D., Ojeda-Fernandez L., Foresta A., De Curtis A., Di Castelnuovo A., Scalvini S., Pierobon A., Gorini A., Valenti L., Luzi L., Racca A., Bandi M., Tremoli E., Menicanti L., Parati G., Pompilio G., Colombo G., Vavassori C., Biondi M. L., Frigerio B., Ravani A., Sansaro D., Coggi D., Romandini A., Giroli M., Giuliani M., Bonmi A., Rondinelli M., Trudu C., Cinieri C., Monturano M., Colazo F., Inviti C., Di Blasi A., Torlasco C., Gilardini L., Soranna D., Zambon A., Perger E., Zanotti L., Badano L., Cova L., Gentilini D., Grappiolo L., Condoreli G., Ferante G., Papa L., Savevski V., Ieva F., Romano I., Remzzi G., Ojeda L., Clerici F., Palumbo A., Genini G. F., Catpano A., Mattioli R., Longhi E., Mantovani L. G., Madotto F., Bonaccio M., Gianfagna F., Ghulam A., Magnacca S., Noro F., Costanzo S., Esposito S., Orlandi S., Persichillo M., Bracone F., Panzera T., Ruggiero E., Parisi R., Franciosa S., Morelli M., De Rita F., Cerletti C., de Gaetano G., Donati M. B., Mencanti L., Romanelli M. M. C., Cerri A., Dubini C., Trevisan M. B., Renna L. V., Milani V., Boveri S., Giubbilini P., Ramputi L., Baroni I., De Angeli G., Riciardi W., Olmetti F., Bussotti M., Gaetano C., Baiardi P., Bachetti T., Balbi M., Comini L., Lorenzoni M., Olivares A., Traversi E., Garre C., Sideri R., Clemenza F., Gentile G., Caruana G., Cuscino N., Di Gesaro G., Greco A., Loddo I., Tuzzolino F., Ucelli A., Palombo D., Spinella G., Mozzetta G., Ameri P., Zoppoli G., Finotello A., Porto I., Pratesi G., Bladini F., Spnardi L., Clerici M., Pelusi S., Bianco C., Carpani R., Periti G., Margarita S., Lanza G. A., Severino A., Pedicino D., D'Amario D., D'Aiello A., Vinci R., Bonanni A., Brecciaroli M., Filomia S., Pastorino R., Boccia S., Urbani A., Sanguinetti M., Santoliquido A., Proto L., Tarquini D., Grimaldi M. C., Leonardi S., Elia A., Currao A., Urtis M., Di Toro A., Giuliani L., Caminiti G., Marcolongo F., Sposato B., Guadagni F., Morsella V., Marziale A., Protti G., Baldassarre, D, Iacoviello, L, Baetta, R, Roncaglioni, M, Condorelli, G, Remuzzi, G, Gensini, G, Frati, L, Ricciardi, W, Conaldi, P, Uccelli, A, Blandini, F, Bosari, S, Scambia, G, Fini, M, Di Malta, A, Amato, M, Veglia, F, Bonomi, A, Klersy, C, Colazzo, F, Pengo, M, Gorini, F, Auteri, L, Ferrante, G, Baviera, M, Ambrosio, G, Catapano, A, Gialluisi, A, Malavazos, A, Castelvecchio, S, Corsi-Romanelli, M, Cardani, R, La Rovere, M, Agnese, V, Pane, B, Prati, D, Spinardi, L, Liuzzo, G, Arbustini, E, Volterrani, M, Visconti, M, Werba, J, Genovese, S, Bilo, G, Invitti, C, Di Blasio, A, Lombardi, C, Faini, A, Rosa, D, Ojeda-Fernandez, L, Foresta, A, De Curtis, A, Di Castelnuovo, A, Scalvini, S, Pierobon, A, Gorini, A, Valenti, L, Luzi, L, Racca, A, Bandi, M, Tremoli, E, Menicanti, L, Parati, G, Pompilio, G, Colombo, G, Vavassori, C, Biondi, M, Frigerio, B, Ravani, A, Sansaro, D, Coggi, D, Romandini, A, Giroli, M, Giuliani, M, Bonmi, A, Rondinelli, M, Trudu, C, Cinieri, C, Monturano, M, Colazo, F, Inviti, C, Di Blasi, A, Torlasco, C, Gilardini, L, Soranna, D, Zambon, A, Perger, E, Zanotti, L, Badano, L, Cova, L, Gentilini, D, Grappiolo, L, Condoreli, G, Ferante, G, Papa, L, Savevski, V, Ieva, F, Romano, I, Remzzi, G, Ojeda, L, Clerici, F, Palumbo, A, Genini, G, Catpano, A, Mattioli, R, Longhi, E, Mantovani, L, Madotto, F, Bonaccio, M, Gianfagna, F, Ghulam, A, Magnacca, S, Noro, F, Costanzo, S, Esposito, S, Orlandi, S, Persichillo, M, Bracone, F, Panzera, T, Ruggiero, E, Parisi, R, Franciosa, S, Morelli, M, De Rita, F, Cerletti, C, de Gaetano, G, Donati, M, Mencanti, L, Romanelli, M, Cerri, A, Dubini, C, Trevisan, M, Renna, L, Milani, V, Boveri, S, Giubbilini, P, Ramputi, L, Baroni, I, De Angeli, G, Riciardi, W, Olmetti, F, Bussotti, M, Gaetano, C, Baiardi, P, Bachetti, T, Balbi, M, Comini, L, Lorenzoni, M, Olivares, A, Traversi, E, Garre, C, Sideri, R, Clemenza, F, Gentile, G, Caruana, G, Cuscino, N, Di Gesaro, G, Greco, A, Loddo, I, Tuzzolino, F, Ucelli, A, Palombo, D, Spinella, G, Mozzetta, G, Ameri, P, Zoppoli, G, Finotello, A, Porto, I, Pratesi, G, Bladini, F, Spnardi, L, Clerici, M, Pelusi, S, Bianco, C, Carpani, R, Periti, G, Margarita, S, Lanza, G, Severino, A, Pedicino, D, D'Amario, D, D'Aiello, A, Vinci, R, Bonanni, A, Brecciaroli, M, Filomia, S, Pastorino, R, Boccia, S, Urbani, A, Sanguinetti, M, Santoliquido, A, Proto, L, Tarquini, D, Grimaldi, M, Leonardi, S, Elia, A, Currao, A, Urtis, M, Di Toro, A, Giuliani, L, Caminiti, G, Marcolongo, F, Sposato, B, Guadagni, F, Morsella, V, Marziale, A, Protti, G, Baldassarre D., Iacoviello L., Baetta R., Roncaglioni M. C., Condorelli G., Remuzzi G., Gensini G., Frati L., Ricciardi W., Conaldi P. G., Uccelli A., Blandini F., Bosari S., Scambia G., Fini M., Di Malta A., Amato M., Veglia F., Bonomi A., Klersy C., Colazzo F., Pengo M., Gorini F., Auteri L., Ferrante G., Baviera M., Ambrosio G., Catapano A., Gialluisi A., Malavazos A. E., Castelvecchio S., Corsi-Romanelli M. M., Cardani R., La Rovere M. T., Agnese V., Pane B., Prati D., Spinardi L., Liuzzo G., Arbustini E., Volterrani M., Visconti M., Werba J. P., Genovese S., Bilo G., Invitti C., Di Blasio A., Lombardi C., Faini A., Rosa D., Ojeda-Fernandez L., Foresta A., De Curtis A., Di Castelnuovo A., Scalvini S., Pierobon A., Gorini A., Valenti L., Luzi L., Racca A., Bandi M., Tremoli E., Menicanti L., Parati G., Pompilio G., Colombo G., Vavassori C., Biondi M. L., Frigerio B., Ravani A., Sansaro D., Coggi D., Romandini A., Giroli M., Giuliani M., Bonmi A., Rondinelli M., Trudu C., Cinieri C., Monturano M., Colazo F., Inviti C., Di Blasi A., Torlasco C., Gilardini L., Soranna D., Zambon A., Perger E., Zanotti L., Badano L., Cova L., Gentilini D., Grappiolo L., Condoreli G., Ferante G., Papa L., Savevski V., Ieva F., Romano I., Remzzi G., Ojeda L., Clerici F., Palumbo A., Genini G. F., Catpano A., Mattioli R., Longhi E., Mantovani L. G., Madotto F., Bonaccio M., Gianfagna F., Ghulam A., Magnacca S., Noro F., Costanzo S., Esposito S., Orlandi S., Persichillo M., Bracone F., Panzera T., Ruggiero E., Parisi R., Franciosa S., Morelli M., De Rita F., Cerletti C., de Gaetano G., Donati M. B., Mencanti L., Romanelli M. M. C., Cerri A., Dubini C., Trevisan M. B., Renna L. V., Milani V., Boveri S., Giubbilini P., Ramputi L., Baroni I., De Angeli G., Riciardi W., Olmetti F., Bussotti M., Gaetano C., Baiardi P., Bachetti T., Balbi M., Comini L., Lorenzoni M., Olivares A., Traversi E., Garre C., Sideri R., Clemenza F., Gentile G., Caruana G., Cuscino N., Di Gesaro G., Greco A., Loddo I., Tuzzolino F., Ucelli A., Palombo D., Spinella G., Mozzetta G., Ameri P., Zoppoli G., Finotello A., Porto I., Pratesi G., Bladini F., Spnardi L., Clerici M., Pelusi S., Bianco C., Carpani R., Periti G., Margarita S., Lanza G. A., Severino A., Pedicino D., D'Amario D., D'Aiello A., Vinci R., Bonanni A., Brecciaroli M., Filomia S., Pastorino R., Boccia S., Urbani A., Sanguinetti M., Santoliquido A., Proto L., Tarquini D., Grimaldi M. C., Leonardi S., Elia A., Currao A., Urtis M., Di Toro A., Giuliani L., Caminiti G., Marcolongo F., Sposato B., Guadagni F., Morsella V., Marziale A., and Protti G.

Abstract

Introduction Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking. Methods and analysis The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners' offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed. Ethics and dissemination This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study's

Published
2023

5. Ceftolozane/Tazobactam for Treatment of Severe ESBL-Producing

Author

Bassetti, M., Vena, A., Giacobbe, D. R., Falcone, M., Tiseo, G., Giannella, M., Pascale, R., Meschiari, M., Digaetano, M., Oliva, A., Rovelli, C., Carannante, N., Losito, A. R., Carbonara, S., Mariani, M. F., Mastroianni, A., Angarano, G., Tumbarello, M., Tascini, C., Grossi, P., Mastroianni, C. M., Mussini, C., Viale, P., Menichetti, F., Viscoli, C., Russo, A., Verdenelli, S., Fabiani, S., Castaldo, N., Pecori, D., Carnellutti, A., Givone, F., Graziano, E., Merelli, M., Cadeo, B., Peghin, M., Cattelan, A., Cipriani, L., Coletto, D., Gianluca, R., Ciardi, M. R., Ajassa, C., Tieghi, T., Pontino, P., Raffaelli, F., Artioli, S., Caruana, G., Luzzati, R., Bontempo, G., Petrosillo, N., Capone, A., Rizzardini, G., Coen, M., Passerini, M., Guadagnino, G., Urso, F., Borgia, G., Gentile, I., Maraolo, A. E., Crapis, M., Venturini, S., Parruti, G., Trave, F., Girardis, M., Cascio, A., Gioe, C., Anselmo, M., Malfatto, E., Bassetti, Matteo, Vena, Antonio, Giacobbe, Daniele Roberto, Falcone, Marco, Tiseo, Giusy, Giannella, Maddalena, Pascale, Renato, Meschiari, Marianna, Digaetano, Margherita, Oliva, Alessandra, Rovelli, Cristina, Carannante, Novella, Losito, Angela Raffaella, Carbonara, Sergio, Mariani, Michele Fabiano, Mastroianni, Antonio, Angarano, Gioacchino, Tumbarello, Mario, Tascini, Carlo, Grossi, Paolo, Mastroianni, Claudio Maria, Mussini, Cristina, Viale, Pierluigi, Menichetti, Francesco, Viscoli, Claudio, Russo, Alessandro, Bassetti M., Vena A., Giacobbe D.R., Falcone M., Tiseo G., Giannella M., Pascale R., Meschiari M., Digaetano M., Oliva A., Rovelli C., Carannante N., Losito A.R., Carbonara S., Mariani M.F., Mastroianni A., Angarano G., Tumbarello M., Tascini C., Grossi P., Mastroianni C.M., Mussini C., Viale P., Menichetti F., Viscoli C., Russo A., Verdenelli S., Fabiani S., Castaldo N., Pecori D., Carnellutti A., Givone F., Graziano E., Merelli M., Cadeo B., Peghin M., Cattelan A., Cipriani L., Coletto D., Gianluca R., Ciardi M.R., Ajassa C., Tieghi T., Pontino P., Raffaelli F., Artioli S., Caruana G., Luzzati R., Bontempo G., Petrosillo N., Capone A., Rizzardini G., Coen M., Passerini M., Guadagnino G., Urso F., Borgia G., Gentile I., Maraolo A.E., Crapis M., Venturini S., Parruti G., Trave F., Girardis M., Cascio A., Gioe C., Anselmo M., Malfatto E., Russo, Alessandro &amp, and Luzzati, R.

Subjects
medicine.medical_specialty, ceftolozane/tazobactam, medicine.medical_treatment, CRRT, Tazobactam, Enterobacterales, Enterobacterale, Internal medicine, ESBL, septic shock, Major Article, medicine, Clinical endpoint, Renal replacement therapy, business.industry, Septic shock, Retrospective cohort study, Odds ratio, medicine.disease, Ceftolozane/tazobactam, AcademicSubjects/MED00290, Infectious Diseases, Oncology, Ceftolozane, business, Empiric therapy, medicine.drug
Abstract

Background Few data are reported in the literature about the outcome of patients with severe extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) infections treated with ceftolozane/tazobactam (C/T), in empiric or definitive therapy. Methods A multicenter retrospective study was performed in Italy (June 2016–June 2019). Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to ESBL-E infection and lack of microbiological evidence of infection. The primary end point was to identify predictors of clinical failure of C/T therapy. Results C/T treatment was documented in 153 patients: pneumonia was the most common diagnosis (n = 46, 30%), followed by 34 cases of complicated urinary tract infections (22.2%). Septic shock was observed in 42 (27.5%) patients. C/T was used as empiric therapy in 46 (30%) patients and as monotherapy in 127 (83%) patients. Favorable clinical outcome was observed in 128 (83.7%) patients; 25 patients were considered to have failed C/T therapy. Overall, 30-day mortality was reported for 15 (9.8%) patients. At multivariate analysis, Charlson comorbidity index >4 (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.9–3.5; P = .02), septic shock (OR, 6.2; 95% CI, 3.8–7.9; P < .001), and continuous renal replacement therapy (OR, 3.1; 95% CI, 1.9–5.3; P = .001) were independently associated with clinical failure, whereas empiric therapy displaying in vitro activity (OR, 0.12; 95% CI, 0.01–0.34; P < .001) and adequate source control of infection (OR, 0.42; 95% CI, 0.14–0.55; P < .001) were associated with clinical success. Conclusions Data show that C/T could be a valid option in empiric and/or targeted therapy in patients with severe infections caused by ESBL-producing Enterobacterales. Clinicians should be aware of the risk of clinical failure with standard-dose C/T therapy in septic patients receiving CRRT.

Published
2020

7. Pancreaticoduodenal arteries aneurysms: Evaluation of frequency and association with celiac artery stenosis due to compression by median arcuate ligament

Author

Caruana G., Cannella R., Giambelluca D., Picone D., Lo Re G., Grassedonio E., Midiri M., Salvaggio G., Caruana G., Cannella R., Giambelluca D., Picone D., Lo Re G., Grassedonio E., Midiri M., and Salvaggio G.

Subjects
Superior mesenteric artery, Median arcuate ligament syndrome, Celiac artery, Computed tomography angiography, Aneurysm
Abstract

The aim of the study is to evaluate the prevalence of pancreaticoduodenal arteries (PDA) aneurysms in a large population, and to define possible correlations with celiac artery stenosis due to compression by the median arcuate ligament. Radiological reports of abdominal contrast-enhanced CT scans of 18,180 patients were scrutinized to identify patients with true PDA aneurysms. Two abdominal radiologists classified the aneurysms according to size, location and morphology and scored the presence of celiac artery stenosis due to either median arcuate ligament compression or atherosclerotic disease. Eleven true PDA aneurysms were identified in 10 patients. Nine out of 10 patients had stenosis of the celiac artery, in which 8 cases (80%) was due to compression by the median arcuate ligament of the diaphragm, which likely represents the most common underlying etiology. In our population, the prevalence of reported PDA aneurysms was 0.055.

Published
2019

12. Validation of a Three-Dimensional Method for Counting and Sizing Podocytes in Whole Glomeruli.

Author

Bertram J.F., Cullen-McEwen L.A., Caruana G., Hokke S.N., Li J., Firth S.D., Harper I.S., Nikolic-Paterson D.J., Schulze K.E., van der Wolde J.W., Puelles V.G., Short K.M., Wong M.N., Bensley J.G., Bertram J.F., Cullen-McEwen L.A., Caruana G., Hokke S.N., Li J., Firth S.D., Harper I.S., Nikolic-Paterson D.J., Schulze K.E., van der Wolde J.W., Puelles V.G., Short K.M., Wong M.N., and Bensley J.G.

Abstract

Podocyte depletion is sufficient for the development of numerous glomerular diseases and can be absolute (loss of podocytes) or relative (reduced number of podocytes per volume of glomerulus). Commonly used methods to quantify podocyte depletion introduce bias, whereas gold standard stereologic methodologies are time consuming and impractical. We developed a novel approach for assessing podocyte depletion in whole glomeruli that combines immunofluorescence, optical clearing, confocal microscopy, and three-dimensional analysis. We validated this method in a transgenic mouse model of selective podocyte depletion, in which we determined dose-dependent alterations in several quantitative indices of podocyte depletion. This new approach provides a quantitative tool for the comprehensive and time-efficient analysis of podocyte depletion in whole glomeruli.Copyright © 2016 by the American Society of Nephrology.

Published
2017

13. Validation of a three-dimensional method for counting and sizing podocytes in whole glomeruli.

Author

Hokke S.N., Nikolic-Paterson D.J., Firth S.D., Cullen-McEwen L.A., Caruana G., Li J., Bertram J.F., Harper I.S., Puelles V.G., Van Der Wolde J.W., Schulze K.E., Short K.M., Wong M.N., Bensley J.G., Hokke S.N., Nikolic-Paterson D.J., Firth S.D., Cullen-McEwen L.A., Caruana G., Li J., Bertram J.F., Harper I.S., Puelles V.G., Van Der Wolde J.W., Schulze K.E., Short K.M., Wong M.N., and Bensley J.G.

Abstract

Podocyte depletion is sufficient for the development of numerous glomerular diseases and can be absolute (loss of podocytes) or relative (reduced number of podocytes per volume of glomerulus). Commonly used methods to quantify podocyte depletion introduce bias, whereas gold standard stereologic methodologies are time consuming and impractical. We developed a novel approach for assessing podocyte depletion in whole glomeruli that combines immunofluorescence, optical clearing, confocal microscopy, and three-dimensional analysis. We validated this method in a transgenic mouse model of selective podocyte depletion, in which we determined dose-dependent alterations in several quantitative indices of podocyte depletion. This new approach provides a quantitative tool for the comprehensive and time-efficient analysis of podocyte depletion in whole glomeruli.Copyright © 2016 by the American Society of Nephrology.

Published
2017

14. gSched: A resource aware Hadoop scheduler for heterogeneous cloud computing environments

Author

Caruana, G, Li, M, Qi, M, Khan, M, and Rana, O

Subjects
Resource Awareness, MapReduce, Cloud Computing, Cost Effective Computing, Task Scheduling
Abstract

MapReduce has become a major programming model for data-intensive applications in cloud computing environments. Hadoop, an open source implementation of MapReduce, has been adopted by an increasingly wide user community. However, Hadoop suffers from task scheduling performance degradation in heterogeneous contexts because of its homogeneous design focus. This paper presents gSched, a resource-aware Hadoop scheduler that takes into account both the heterogeneity of computing resources and provisioning charges in task allocation in cloud computing environments. gSched is initially evaluated in an experimental Hadoop cluster and demonstrates enhanced performance compared with the default Hadoop scheduler. Further evaluations are conducted on the Amazon EC2 cloud that demonstrates the effectiveness of gSched in task allocation in heterogeneous cloud computing environments.

Published
2016

15. Mechanical and microstructural evolution of a 3xxx aluminium alloy made by hazelett process

Author

Salvador, M. D., Amigó, V., Reig, L., Bloem, C., Carsí, M., and Caruana, G.

Subjects
lcsh:TN1-997, propiedades mecánicas, Mining engineering. Metallurgy, Propiedades mecánicas, AA3005, aa3005, TN1-997, Recristalización, Recrystallization, Mechanical properties, proceso hazelett, Proceso Hazelett, Precipitation, Microstructural characterization, Caracterización microestructural, recristalización, precipitación, Precipitación, caracterización microestructural, Hazelett process, lcsh:Mining engineering. Metallurgy
Abstract

10 páginas, 9 figuras, 3 tablas., [ES] El presente trabajo expone los resultados del estudio térmico, microestructural y mecánico realizado en una aleación AA3005 sometida a los diferentes estados del proceso Hazelett. Se estudia, desde la salida de la colada continua, pasando por distintos estados de deformación plástica en caliente, hasta alcanzar en la última laminación un espesor de 1,5 mm. Se realiza la observación por microscopia óptica y electrónica de barrido de las diferentes planchas procedentes tanto de la colada como de las posteriores laminaciones. Así mismo, la aplicación de la calorimetría diferencial de barrido ha permitido conocer los diferentes estados térmicos de las chapas, completando dicha información mediante su observación en el microscopio electrónico de transmisión. La interacción entre los diferentes procesos que ocurren en el material durante su producción determina el estado microestructural final de la lámina, condicionante tanto de sus propiedades mecánicas, determinadas mediante ensayos de dureza y tracción, como de los posteriores procesos de conformado. La evolución de los procesos de recristalización y precipitación provocan un incremento de las propiedades mecánicas a lo largo del proceso de fabricación., [EN] This paper presents the thermal, microstructural and mechanical changes of a AA3005 aluminium alloy during the different stages of manufacturing process, from continuous cast billet (20 mm thick) , along the different plastic deformation stages, till the last lamination (1.5 mm thick). The optical and scanning electron microscopy study of the different sheets obtained both in the cast and after each lamination, as well as the differential scanning calorimetry study has allowed us to identify the different thermal states of the sheets. The information provided by this technique was completed by transmision electron microscopy analysis. The interaction between the different processes occurred in the material during its manufacturing determines its final microstructural state, its mechanical properties, evaluated with hardness and tensile tests, as well as its behaviour for later forming processes. The recrystallization and precipitation phenomena increase mechanical properties during the manufacturing process.

Published
2007

17. Smad3 deficiency protects mice from obesity-induced podocyte injury that precedes insulin resistance.

Author

Li J., Nikolic-Paterson D.J., Jiang X., Ren Y., Fu P., Puelles V.G., Caruana G., Bertram J.F., Sleeman M.W., Sun Y.B.Y., Qu X., Howard V., Dai L., Li J., Nikolic-Paterson D.J., Jiang X., Ren Y., Fu P., Puelles V.G., Caruana G., Bertram J.F., Sleeman M.W., Sun Y.B.Y., Qu X., Howard V., and Dai L.

Abstract

Signaling by TGF-beta/Smad3 plays a key role in renal fibrosis. As obesity is one of the major risk factors of chronic and end-stage renal disease, we studied the role of Smad3 signaling in the pathogenesis of obesity-related renal disease. After switching to a high fat diet, the onset of Smad3 C-terminal phosphorylation, increase in albuminuria, and the early stages of peripheral and renal insulin resistance occurred at 1 day, and 4 and 8 weeks, respectively, in C57BL/6 mice. The loss of synaptopodin, a functional marker of podocytes, and phosphorylation of the Smad3 linker region (T179 and S213) appeared after 4 weeks of the high fat diet. This suggests a temporal pattern of Smad3 signaling activation leading to kidney injury and subsequent insulin resistance in the development of obesity-related renal disease. In vivo, Smad3 knockout attenuated the high fat diet-induced proteinuria, renal fibrosis, overall podocyte injury, and mitochondrial dysfunction in podocytes. In vitro palmitate caused a rapid activation of Smad3 in 30 min, loss of synaptopodin in 2 days, and impaired insulin signaling in 3 days in isolated mouse podocytes. Blockade of either Smad3 phosphorylation by SIS3 (a Smad3 inhibitor) or T179 phosphorylation by flavopiridol (a CDK9 inhibitor) prevented the palmitate-induced loss of synaptopodin and mitochondrial function in podocytes. Thus, Smad3 signaling plays essential roles in obesity-related renal disease and may be a novel therapeutic target.Copyright © 2015 International Society of Nephrology.

Published
2015

18. The SMAD3/SMAD4/CDK9 complex promotes renal fibrosis in mice with unilateral ureteral obetruction.

Author

Caruana G., Bertram J.F., Li J., Qu X., Jiang M., Sun Y.B., Nikolic-Paterson D.J., Jiang X., Caruana G., Bertram J.F., Li J., Qu X., Jiang M., Sun Y.B., Nikolic-Paterson D.J., and Jiang X.

Abstract

Aim: To investigate the functional roles of Smad3/Smad4/CDK9 complex in the pathogenesis of renal fibrosis in mice with Unilateral Ureteral Obstruction (UUO). Background(s): TGF-beta1/Smad signalling plays a central role in the pathogenesis of renal fibrosis. Smad3 and Smad4 are pro-fibrotic, while Smad2 is anti-fibrotic. However, these Smads form heterogeneous complexes the functions of which are poorly understood. Smad3 consists of MH1 and MH2 domains which are connected by a linker region. In vitro studies have demonstrated that CDK9-driven Smad3 linker phosphorylation is Smad4-dependent and requires Smad3 C-terminal phosphorylation. Thus Smad3, Smad4 and CDK9 may form transcriptional complexes. Method(s): The functional roles of Smad3/Smad4/CDK9 complex were investigated in renal fibroblasts and in UUO. Result(s): Mice heterozygous for Smad3&4 (Smad3/4+/-) exhibited substantial protection from renal fibrosis on day 7 UUO, whereas Smad2/3+/- and Smad2/4+/- mice showed only modest protection. Formation of Smad3/Smad4/CDK9 complexes was an early event following UUO in wild type mice, which involved nuclear phosphorylation of the linker regions of Smad3. Smad3 or Smad4 deficiency significantly decreased the formation of Smad4/CDK9 or Smad3/CDK9 complex, Smad3 linker phosphorylation as well as renal fibrosis but at different degrees. In vitro, TGF-beta1 stimulation of collagen I promoter activity involved formation of Smad3/Smad4/CDK9 complexes, and over-expression of each component gave additive increases in collagen promoter activity. Co-administration of a CDK9 inhibitor and a specific Smad3 inhibitor achieved better protection from TGF-beta1-induced fibrotic response in vitro and renal interstitial fibrosis in UUO than administration of a single inhibitor. Conclusion(s): We have identified that the formation of Smad3/Smad4/CDK9 complex drives renal fibrosis in the UUO model. Formation of this complex represents a novel target for anti-fibrotic therapies.

Published
2015

19. Podocyte adaptation in a mouse model of conditional podocyte depletion.

Author

Cullen-Mcewen L.M., Nikolic-Paterson D.J., Van Der Wolde J., Bertram J.F., Caruana G., Puelles V.G., Hokke S.N., Cullen-Mcewen L.M., Nikolic-Paterson D.J., Van Der Wolde J., Bertram J.F., Caruana G., Puelles V.G., and Hokke S.N.

Abstract

Aim: To determine the adaptive capacity of podocytes in the context of podocyte depletion. Background(s): Podocyte depletion plays a central role in the development and progression of the majority of glomerular diseases. However, the ability of remaining podocytes to adapt and preserve glomerular function in the setting of podocyte depletion remains unclear. Method(s): PodCreiDTR mice, which express the human diphtheria toxin (DT) receptor exclusively in podocytes, were injected with DT (30 or 50 ng/kg) to induce mild (<30%) or severe (>40%) podocyte depletion, respectively. Albumin to creatinine ratio (ACR) was measured in spot urine samples. Mice were killed on day 0, 8 or 35 for podocyte analysis (n = 2-6). Total podocyte number and mean podocyte volume were measured in complete glomeruli contained in 800 mum thick slices using immunofluorescence, tissue clearing and confocal microscopy. Result(s): PodCreiDTR mice given 30 ng/kg DT (mild podocyte depletion) showed a 6-fold increase in ACR on days 6-8 that returned to normal by day 20 with an increase in mean podocyte volume of 27% (P = 0.03 vs control iDTR mice) by day 35. In contrast, 50 ng/kg DT (severe podocyte depletion) induced a 13-fold increase in ACR in days 6-8, which did not resolve and was associated with the development of glomerulosclerosis and a doubling in mean podocyte volume (P < 0.001 vs control iDTR mice) by day 35. Conclusion(s): Combining the PodCreiDTR mouse model with novel analysis of complete glomeruli provides a powerful approach to defining the adaptive capacity of podocytes. The resolution of albuminuria following mild podocyte depletion is associated with mild podocyte hypertrophy. However, even with a substantial podocyte hypertrophic response, severe podocyte depletion leads to persistent albuminuria and glomerulosclerosis.

Published
2015

20. Copy-number variation associated with congenital anomalies of the kidney and urinary tract.

Author

James P.A., Bertram J.F., Caruana G., Wong M.N., Walker A., Heloury Y., Webb N., Johnstone L., Burgess T., James P.A., Bertram J.F., Caruana G., Wong M.N., Walker A., Heloury Y., Webb N., Johnstone L., and Burgess T.

Abstract

Background: The most common cause of end-stage renal disease in children can be attributed to congenital anomalies of the kidney and urinary tract (CAKUT). Despite this high incidence of disease, the genetic mutations responsible for the majority of CAKUT cases remain unknown. Method(s): To identify novel genomic regions associated with CAKUT, we screened 178 children presenting with the entire spectrum of structural anomalies associated with CAKUT for submicroscopic chromosomal imbalances (deletions or duplications) using single-nucleotide polymorphism (SNP) microarrays. Result(s): Copy-number variation (CNV) was detected in 10.1 % (18/178) of the patients; in 6.2 % of the total cohort, novel duplications or deletions of unknown significance were identified, and the remaining 3.9 % harboured CNV of known pathogenicity. CNVs were inherited in 90 % (9/10) of the families tested. In this cohort, patients diagnosed with multicystic dysplastic kidney (30 %) and posterior urethral valves (24 %) had a higher incidence of CNV. Conclusion(s): The genes contained in the altered genomic regions represent novel candidates for CAKUT. This study has demonstrated that a significant proportion of patients with CAKUT harbour submicroscopic chromosomal imbalances, warranting screening in clinics for CNV.Copyright © 2014, IPNA.

Published
2015

21. The Smad3/Smad4/CDK9 complex promotes renal fibrosis in mice with unilateral ureteral obstruction.

Author

Qu X., Nikolic-Paterson D.J., Li J., Bertram J.F., Caruana G., Dai L., Wang D., Ren Y., Fu P., Jiang X., Sun Y.B.Y., Jiang M., Qu X., Nikolic-Paterson D.J., Li J., Bertram J.F., Caruana G., Dai L., Wang D., Ren Y., Fu P., Jiang X., Sun Y.B.Y., and Jiang M.

Abstract

Transforming growth factor-beta1 (TGF-beta1)/Smad signaling has a central role in the pathogenesis of renal fibrosis. Smad3 and Smad4 are pro-fibrotic, while Smad2 is anti-fibrotic. However, these Smads form heterogeneous complexes, the functions of which are poorly understood. Here we studied Smad complex function in renal fibrosis using the mouse model of unilateral ureteric obstruction. Mice heterozygous for Smad3/4 (Smad3/4 +/-) exhibited substantial protection from renal fibrosis through day 7 of obstruction, whereas Smad2/3 +/- and Smad2/4 +/- mice showed only modest protection. Formation of Smad3/Smad4/CDK9 complexes was an early event following obstruction in wild-type mice, which involved nuclear phosphorylation of the linker regions of Smad3. Significantly, Smad3 or Smad4 deficiency decreased the formation of Smad4/CDK9 or Smad3/CDK9 complex, Smad3 linker phosphorylation, and fibrosis but at different degrees. In vitro, TGF-beta1 stimulation of collagen I promoter activity involved formation of Smad3/Smad4/CDK9 complexes, and overexpression of each component gave additive increases in collagen promoter activity. Co-administration of a CDK9 inhibitor and Smad3-specific inhibition achieved better protection from TGF-beta1-induced fibrotic response in vitro and renal interstitial fibrosis in vivo. Thus formation of Smad3/Smad4/CDK9 complex drives renal fibrosis during ureteral obstruction. Formation of this complex represents a novel target for antifibrotic therapies.Copyright © 2015 International Society of Nephrology.

Published
2015

22. A protocol for the identification and validation of novel genetic causes of kidney disease

Author

Mallett, A, Patel, C, Maier, B, McGaughran, J, Gabbett, M, Takasato, M, Cameron, A, Trnka, P, Alexander, SI, Rangan, G, Tchan, MC, Caruana, G, John, G, Quinlan, C, McCarthy, HJ, Hyland, V, Hoy, WE, Wolvetang, E, Taft, R, Simons, C, Healy, H, Little, M, Mallett, A, Patel, C, Maier, B, McGaughran, J, Gabbett, M, Takasato, M, Cameron, A, Trnka, P, Alexander, SI, Rangan, G, Tchan, MC, Caruana, G, John, G, Quinlan, C, McCarthy, HJ, Hyland, V, Hoy, WE, Wolvetang, E, Taft, R, Simons, C, Healy, H, and Little, M

Abstract

BACKGROUND: Genetic renal diseases (GRD) are a heterogeneous and incompletely understood group of disorders accounting for approximately 10 % of those diagnosed with kidney disease. The advent of Next Generation sequencing and new approaches to disease modelling may allow the identification and validation of novel genetic variants in patients with previously incompletely explained or understood GRD. METHODS/DESIGN: This study will recruit participants in families/trios from a multidisciplinary sub-specialty Renal Genetics Clinic where known genetic causes of GRD have been excluded or where genetic testing is not available. After informed patient consent, whole exome and/or genome sequencing will be performed with bioinformatics analysis undertaken using a customised variant assessment tool. A rigorous process for participant data management will be undertaken. Novel genetic findings will be validated using patient-derived induced pluripotent stem cells via differentiation to renal and relevant extra-renal tissue phenotypes in vitro. A process for managing the risk of incidental findings and the return of study results to participants has been developed. DISCUSSION: This investigator-initiated approach brings together experts in nephrology, clinical and molecular genetics, pathology and developmental biology to discover and validate novel genetic causes for patients in Australia affected by GRD without a known genetic aetiology or pathobiology.

Published
2015

24. Regulation of renal fibrosis by Smad3 Thr388 phosphorylation.

Author

Puelles V.G., Li J., Nikolic-Paterson D.J., Caruana G., Qu X., Li X., Zheng Y., Ren Y., Puelles V.G., Li J., Nikolic-Paterson D.J., Caruana G., Qu X., Li X., Zheng Y., and Ren Y.

Abstract

Transforming growth factor-beta (TGF-beta) promotes tissue fibrosis via receptor-mediated phosphorylation of the receptor-activated Smad2/3, together with Smad4. Of these, Smad3 plays a major profibrotic role in mouse models of tissue fibrosis. Transcriptional activity of the Smad3 protein is regulated by phosphorylation of residues in the C-terminal domain and the linker region. Herein, we examined the role of a novel phosphorylation site within the MH2 domain (T388) in the regulation of Smad3 activity. Confocal microscopy using an Smad3 phosphorylated T388-specific antibody identified phosphorylation of Smad3 T388 in myofibroblasts and tubular epithelial cells in human focal and segmental glomerulosclerosis and mouse models of unilateral ureteric obstruction and diabetic nephropathy, whereas phosphorylated T388 was largely absent in normal kidney. In vitro, TGF-beta1 induced phosphorylation of Smad3 T388 in a biphasic pattern. A point mutation of T388/V in an Smad3 construct demonstrated that phosphorylation of T388 promotes Smad3 binding to Smad4 and CDK8, but was not necessary for nuclear translocation. Furthermore, T388 phosphorylation was required for TGF-beta-induced collagen I gene promoter activity and extracellular matrix production in cultured fibroblasts. In conclusion, our study identifies phosphorylation of T388 in the Smad3 MH2 domain as an important mechanism that regulates the profibrotic TGF-beta/Smad3 signaling pathway, which has direct relevance to human and experimental fibrotic kidney disease.

Published
2014

25. Evolución de las propiedades mecánicas durante la cristalización de cintas amorfas Mg-Ni

Author

Pérez, P., Garcés, G., Caruana, G., and Adeva, P.

Subjects
Aleaciones de magnesio, Propiedades mecánicas, Magnesium alloys, Amorphous, Mechanical properties, Amorfos
Abstract

The evolution of mechanical properties with temperature of rapidly solidified Mg23Ni and Mg-35Ni (mass %) have been studied by tensile tests. Both alloys crystallize in the test temperature range (room temperature-350 °C). The process takes place in two steps for Mg23Ni and in one step for Mg35Ni. The microstructural changes in the alloys by the crystallisation processes are responsible for mechanical properties evolution with temperature as well as for differences observed between both alloys. En este trabajo se estudia la evolución de las propiedades mecánicas con la temperatura, mediante ensayos de tracción, de dos aleaciones amorfas Mg-23Ni y Mg-35Ni (% en masa) procesadas por solidificación rápida. Las dos aleaciones experimentan, en el intervalo de temperaturas de ensayo (temperatura ambiente-350 °C), procesos de cristalización que transcurren en dos etapas, en el caso de la aleación Mg-23Ni, y en una etapa, en la aleación Mg-35Ni. Los cambios microestructurales asociados a los procesos de cristalización son responsables de la variación de las propiedades mecánicas con la temperatura así como de las diferencias observadas entre las dos aleaciones.

Published
2005
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26. bfb, a Novel ENU-Induced blebs Mutant Resulting from a Missense Mutation in Fras1

Author

Kappen, C, Miller, KA, Gordon, CT, Welfare, MF, Caruana, G, Bertram, JF, Bateman, JF, Farlie, PG, Kappen, C, Miller, KA, Gordon, CT, Welfare, MF, Caruana, G, Bertram, JF, Bateman, JF, and Farlie, PG

Abstract

Fras1 is an extracellular matrix associated protein with essential roles in adhesion of epithelia and mesenchyme during early embryonic development. The adhesive function of Fras1 is achieved through interaction with a group of related proteins, Frem 1-3, and a cytoplasmic adaptor protein Grip1. Mutation of each of these proteins results in characteristic epithelial blistering and have therefore become known as "blebs" proteins. Human Fraser syndrome presents with a similar phenotype and the blebs mice have been instrumental in identification of the genetic basis of Fraser syndrome. We have identified a new ENU-induced blebs allele resulting from a novel missense mutation in Fras1. The resulting mouse strain, blood filled blisters (bfb), presents with a classic blebs phenotype but does not exhibit embryonic lethality typical of other blebs mutants and in addition, we report novel palate and sternal defects. Analysis of the bfb phenotype confirms the presence of epithelial-mesenchymal adhesion defects but also supports the emerging role of blebs proteins in regulating signalling during organogenesis. The bfb strain provides new opportunities to investigate the role of Fras1 in development.

Published
2013

27. Cauli: A Mouse Strain with an Ift140 Mutation That Results in a Skeletal Ciliopathy Modelling Jeune Syndrome

Author

Dutcher, SK, Miller, KA, Ah-Cann, CJ, Welfare, MF, Tan, TY, Pope, K, Caruana, G, Freckmann, M-L, Savarirayan, R, Bertram, JF, Dobbie, MS, Bateman, JF, Farlie, PG, Dutcher, SK, Miller, KA, Ah-Cann, CJ, Welfare, MF, Tan, TY, Pope, K, Caruana, G, Freckmann, M-L, Savarirayan, R, Bertram, JF, Dobbie, MS, Bateman, JF, and Farlie, PG

Abstract

Cilia are architecturally complex organelles that protrude from the cell membrane and have signalling, sensory and motility functions that are central to normal tissue development and homeostasis. There are two broad categories of cilia; motile and non-motile, or primary, cilia. The central role of primary cilia in health and disease has become prominent in the past decade with the recognition of a number of human syndromes that result from defects in the formation or function of primary cilia. This rapidly growing class of conditions, now known as ciliopathies, impact the development of a diverse range of tissues including the neural axis, craniofacial structures, skeleton, kidneys, eyes and lungs. The broad impact of cilia dysfunction on development reflects the pivotal position of the primary cilia within a signalling nexus involving a growing number of growth factor systems including Hedgehog, Pdgf, Fgf, Hippo, Notch and both canonical Wnt and planar cell polarity. We have identified a novel ENU mutant allele of Ift140, which causes a mid-gestation embryonic lethal phenotype in homozygous mutant mice. Mutant embryos exhibit a range of phenotypes including exencephaly and spina bifida, craniofacial dysmorphism, digit anomalies, cardiac anomalies and somite patterning defects. A number of these phenotypes can be attributed to alterations in Hedgehog signalling, although additional signalling systems are also likely to be involved. We also report the identification of a homozygous recessive mutation in IFT140 in a Jeune syndrome patient. This ENU-induced Jeune syndrome model will be useful in delineating the origins of dysmorphology in human ciliopathies.

Published
2013

28. Genome-Wide ENU Mutagenesis in Combination with High Density SNP Analysis and Exome Sequencing Provides Rapid Identification of Novel Mouse Models of Developmental Disease

Author

Veitia, RA, Caruana, G, Farlie, PG, Hart, AH, Bagheri-Fam, S, Wallace, MJ, Dobbie, MS, Gordon, CT, Miller, KA, Whittle, B, Abud, HE, Arkell, RM, Cole, TJ, Harley, VR, Smyth, IM, Bertram, JF, Veitia, RA, Caruana, G, Farlie, PG, Hart, AH, Bagheri-Fam, S, Wallace, MJ, Dobbie, MS, Gordon, CT, Miller, KA, Whittle, B, Abud, HE, Arkell, RM, Cole, TJ, Harley, VR, Smyth, IM, and Bertram, JF

Abstract

BACKGROUND: Mice harbouring gene mutations that cause phenotypic abnormalities during organogenesis are invaluable tools for linking gene function to normal development and human disorders. To generate mouse models harbouring novel alleles that are involved in organogenesis we conducted a phenotype-driven, genome-wide mutagenesis screen in mice using the mutagen N-ethyl-N-nitrosourea (ENU). METHODOLOGY/PRINCIPAL FINDINGS: ENU was injected into male C57BL/6 mice and the mutations transmitted through the germ-line. ENU-induced mutations were bred to homozygosity and G3 embryos screened at embryonic day (E) 13.5 and E18.5 for abnormalities in limb and craniofacial structures, skin, blood, vasculature, lungs, gut, kidneys, ureters and gonads. From 52 pedigrees screened 15 were detected with anomalies in one or more of the structures/organs screened. Using single nucleotide polymorphism (SNP)-based linkage analysis in conjunction with candidate gene or next-generation sequencing (NGS) we identified novel recessive alleles for Fras1, Ift140 and Lig1. CONCLUSIONS/SIGNIFICANCE: In this study we have generated mouse models in which the anomalies closely mimic those seen in human disorders. The association between novel mutant alleles and phenotypes will lead to a better understanding of gene function in normal development and establish how their dysfunction causes human anomalies and disease.

Published
2013

29. Sexual dimorphism in mouse metanephroi exposed to 17beta-estradiol in vitro.

Author

McInnes K.J., Walker K.A., Caruana G., Bertram J.F., McInnes K.J., Walker K.A., Caruana G., and Bertram J.F.

Abstract

17beta-Estradiol, the most potent circulating estrogen, has been shown to greatly impact on the development and formation of tissues of the urogenital tract. The adult kidney has previously been shown to be highly responsive to 17beta-estradiol stimulation. However, the direct effect of 17beta-estradiol on kidney development remains unclear. Aim(s): To investigate the direct effect of 17beta-estradiol on male and female metanephric kidney development. Method(s): Whole embryonic-day-12.5 (E12.5) C57Bl/6 male and female mouse metanephroi were cultured in the presence of varying concentrations of 17beta-estradiol (0.1-5.0 nM) for 72 h. Metanephric development was assessed using immunofluorescence labeling techniques. The real-time polymerase chain reaction was used to investigate estrogen receptor-alpha (ERalpha), glial-cell-line-derived neurotrophic factor (GDNF) and its associated receptor cRET, transforming growth factor-beta (TGFbeta1), TGFbeta2 and TGFbeta3 mRNA expression levels. Result(s):ERalpha was present in developing metanephroi at E12.5; however, ERbeta was absent. No significant sex difference in ERalpha mRNA expression was observed. Significant increases in the number of ureteric branch points, terminal tips and developing glomeruli were observed in female metanephroi cultured in the presence of 1.0 and 5.0 nM 17beta-estradiol. Conversely, no significant effect was observed in male metanephroi cultured with 17beta-estradiol. GDNF and cRET mRNA expression was increased in both male and female metanephroi, whilst TGFbeta1 and TGFbeta2 mRNA expression was decreased following culture in the presence of 17beta-estradiol. Conclusion(s): This study is the first to establish that the mouse metanephros displays a sexual dimorphism in response to specific concentrations of estrogens. Copyright © 2009 S. Karger AG.

Published
2009

30. Elaboración de aleaciones de Cu-Al-Ni con efecto memoria de forma mediante pulvimetalurgia

Author

Pérez-Sáez, R. B., San Juan, J., Recarte, V., Nó, M. L., Caruana, G., and Ruano, O. A.

Subjects
Memoria de forma, Transformación martensítica, Cu-Al-Ni, Shape memory alloys, Powder metallurgy, Martensitic transformation, Pulvimetalurgia
Abstract

During the production of shape memory alloys, a very fine grain size should be obtained in order to obtain better mechanical properties and a good thermomechanical behaviour during cycling. The classically used grain refiners show some secondary effects on the martensitic transformations that could be at the origin of some technological problems. For this reason, a new processing method by powder metallurgy has been developed for this kind of alloys. The three proceeding stages are described: Atomization, hot isostatic pressing and hot rolling. The microstructure of the materials is characterized. The martensitic transformation and the thermomechanical properties are also studied. En la elaboración de aleaciones Cu-Al-Ni con efecto memoria de forma es importante conseguir un tamaño de grano fino, para mejorar las propiedades mecánicas y el comportamiento durante el ciclado termomecánico. Clásicamente, esto se ha conseguido mediante la adición de refinadores de grano; sin embargo, los efectos secundarios que éstos producen pueden ser problemáticos. Por esta razón, se ha desarrollado un nuevo método de procesado de este tipo de aleaciones mediante pulvimetalurgia. En este trabajo se presenta el proceso de elaboración consistente en tres etapas: atomización, compactación isostática en caliente y laminación en caliente. Se estudia la microestructura del material, se caracteriza la transformación martensítica y se determinan las propiedades termomecánicas.

Published
1998
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31. Influencia del tamaño de partícula de polvo sobre las propiedades mecánicas de la aleación PM Al7075 reforzada con SiCp

Author

Torralba, M., Adeva, P., Lieblich, M., Ibáñez, J., Caruana, G., García-Escorial, A., and González-Doncel, G.

Subjects
Solidificación rápida, Particle size, Al7075-SiCp, Ball mili, Rapid solidification, Materiales compuestos, Tamaño de partícula, Composites, Molino de bolas
Abstract

The influence of powder particle size of 7075 aluminum on the room temperature mechanical properties of 7075-15 vol % SiCp has been studied. The aluminum powder was obtained by argon atomization under rapid solidification conditions. Composite materials were prepared from three different particle sizes, namely: < 50 μm, 50-100 μm and 100-200 μm. These powders were blended with 15 vol % of SiC particles < 5 μm in size by ball milling and then, hot extruded. The best properties of the resulting composites correspond to the material prepared from the smallest particle size. For this case, a clear improvement of the mechanical properties, except for ductility, is obtained. This is attributed to a more homogeneous distribution of the reinforcing SiC particles. Se ha estudiado la influencia del tamaño de partícula de polvo de la aleación de aluminio 7075, obtenido en condiciones de solidificación rápida (SR) por atomización con argón a alta presión, sobre las propiedades mecánicas a temperatura ambiente de un material compuesto 7075-15 % vol SiCp. Para preparar el material compuesto, se utilizaron tres tamaños distintos de partículas de polvo de la aleación: < 50 μm, 50-100 μm y 100-200 μm. Estas fracciones se mezclaron en un molino de bolas con un 15 % vol de partículas de SiC < 5 μm, y luego se extruyeron en caliente. Las mejores propiedades del compuesto se obtienen cuando se utiliza el tamaño más pequeño. En este caso, se produce una clara mejoría de las propiedades mecánicas respecto del mismo material sin reforzar y obtenido por el mismo procedimiento, excepto para la ductilidad. Esta mejora se atribuye principalmente a una dispersión más homogénea de las partículas reforzantes de SiC.

Published
1998
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36. The burden of HIV-Associated neurocognitive disorder (HAND) in post-HAART era: Amultidisciplinary review of the literature

Author

Caruana G, Vidili G, Pa, Serra, Bagella P, Spanu A, Fiore V, Df, Calvisi, Manetti R, Rocchitta G, Susanna Maria F. NUVOLI, Babudieri S, Mm, Simile, and Madeddu G

Subjects
AIDS Dementia Complex, Cost of Illness, Antiretroviral Therapy, Highly Active, Humans
Abstract

The purpose of the present multidisciplinary review is to give an updated insight into the most recent findings regarding the pathophysiology, diagnosis and therapeutics of HIV-associated neurocognitive disorder (HAND).We performed a comprehensive search, through electronic databases (Pubmed - MEDLINE) and search engines (Google Scholar), of peer-reviewed publications (articles and reviews) and conferences proceedings on HAND pathophysiology, diagnosis, and therapy, from 1999 to 2016.It seems to be increasingly clear that neurodegeneration in HIV-1 affected patients is a multi-faceted disease involving numerous factors, from chronic inflammation to central nervous system (CNS) compartmentalization of HIV. Diagnosis of HAND may benefit from both laboratory analysis and advanced specific neuroimaging techniques. As regards HAND therapy, modified HAART combinations and simplification strategies have been tested, while novel exciting frontiers seem to involve the use of nanoparticles with the ability to cross the Blood-Brain Barrier (BBB).Albeit highly active antiretroviral therapy (HAART) allowed a major decrease in morbidity and mortality for AIDS patients, CNS involvement still represents a challenge in HIV patients even today, affecting up to 50% of patients with access to combination antiretroviral therapy (cART). Future studies will have to focus on CNS compartmentalization, drugs' ability to penetrate and suppress viral replication in this compartment, and on new approaches to reduce HIV-associated neuroinflammation.

37. Body fat changes in HIV patients on highly active antiretroviral therapy (HAART): A longitudinal DEXA study

Author

Susanna Maria F. NUVOLI, Caruana, G., Babudieri, S., Solinas, P., Pellicanò, G., Piras, B., Fiore, V., Bagella, P., Calia, G. M., Yue, M., Spanu, A., and Madeddu, G.

Subjects
Male, DEXA, Lipodystrophy, HIV, HIV Infections, HIV, Highly active anti-retroviral therapy (HAART), AIDS, DEXA, Body fat, Lipodystrophy, AIDS, Absorptiometry, Photon, Adipose Tissue, Risk Factors, Body fat, Antiretroviral Therapy, Highly Active, Body Composition, Humans, Female, Longitudinal Studies, Highly active anti-retroviral therapy (HAART), Retrospective Studies
Abstract

We aimed to quantitatively evaluate body fat composition in a group of HIV patients treated with Highly Active Anti-retroviral Therapy (HAART) to ascertain both fat loss and fat distribution changes and to identify possible therapeutic and host related associated risk factors.A total of 180 patients with available total body DEXA scan were assigned to a) Group 1, with clinically evident body fat changes, (BFC) and b) Group 2, without BFC. Clinical and immunovirologic data were collected. We used Student t-test and x2 or Fisher exact test to compare the characteristics of the two groups. Paired t-test was used to compare basal and follow-up data. The relationships between variables were evaluated by calculating Pearson's correlation coefficient and its significance.HAART duration was significantly (p0.0001) higher for patients in Group 1 than in Group 2, as well as PI (p0.02) and NRTI (p0.002) therapy duration. Current CD4 count and CD4 rise from nadir resulted significantly higher in Group 1 than in Group 2 (p0.02 and 0.006, respectively). Whole Body Fat (WBF), Peripheral Fat (PF) and Leg (L) fat negatively correlated with PI and NRTI therapy duration, while Trunk Fat (TF)/PF positively correlated with PI and NNRTI duration. No significant correlation was found, instead, with NNRTI therapy duration. At 5-year follow-up, we registered a further increase in TF, Arms (A) and L fat, especially in PI-treated patients.Body fat changes should always be considered when dealing with HIV-affected patients on HAART. The fat loss seemed to involve mainly peripheral regions, while fat accumulation tendency occurred in the trunk.

40. Liberation index for sphalerite in a differential flotation process for sulphides.

Author

Lopez Gomez F.A., Caruana G., Garcia Carcedo F., Lopez Gomez F.A., Caruana G., and Garcia Carcedo F.

Abstract

In connection with the design of a beneficiation system for a complex sulphide ore from northern Spain containing zinc, lead, copper and iron, a technique was devised for mineral liberation prediction involving automated image analysis of various size fractions of the ore., In connection with the design of a beneficiation system for a complex sulphide ore from northern Spain containing zinc, lead, copper and iron, a technique was devised for mineral liberation prediction involving automated image analysis of various size fractions of the ore.

42. CT angiography for the assessment of EVAR complications : a pictorial review

Author

Gozzo, Cecilia, Caruana, Giovanni, Cannella, Roberto, Farina, Arduino, Giambelluca, Dario, Dinoto, Ettore, Vernuccio, Federica, Basile, Antonio, Midiri, Massimo, Universitat Autònoma de Barcelona, Institut Català de la Salut, [Gozzo C] Radiodiagnostic and Radiotherapy Unit, Department of Medical and Surgical Sciences and Advanced Technologies 'GF Ingrassia', Catania, Italy. [Caruana G] Secció de Neuroradiologia, Servei de Radiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Cannella R] Section of Radiology - BiND, University Hospital 'Paolo Giaccone', University of Palermo, Palermo, Italy. Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy. [Farina A] Vascular Surgery Unit ARNAS Civico Di Cristina Benfratelli, Palermo, Italy. [Giambelluca D] Section of Radiology, Asp Siracusa, Ospedale Umberto I, Siracusa, Italy. [Dinoto E] Vascular Surgery Unit AOUP Policlinico ‘P. Giaccone’, Palermo, Italy, Vall d'Hebron Barcelona Hospital Campus, Gozzo C., Caruana G., Cannella R., Farina A., Giambelluca D., Dinoto E., Vernuccio F., Basile A., and Midiri M.

Subjects
intervenciones quirúrgicas::procedimientos quirúrgicos cardiovasculares::procedimientos quirúrgicos vasculares::procedimientos endovasculares [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Cardiovascular Diseases::Vascular Diseases::Aneurysm::Aortic Aneurysm::Aortic Aneurysm, Abdominal [DISEASES], Aortic aneurysm, R895-920, diagnóstico::técnicas y procedimientos diagnósticos::diagnóstico por imagen::interpretación de imágenes asistida por ordenador::tomografía computarizada por rayos X::angiografía por tomografía computarizada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Otros calificadores::Otros calificadores::/diagnóstico por imagen [Otros calificadores], enfermedades cardiovasculares::enfermedades vasculares::aneurisma::aneurisma de la aorta::aneurisma de la aorta abdominal [ENFERMEDADES], Blood vessel prosthesis implantation, Surgical Procedures, Operative::Cardiovascular Surgical Procedures::Vascular Surgical Procedures::Endovascular Procedures [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Medical physics. Medical radiology. Nuclear medicine, Vasos sanguinis - Cirurgia, Endovascular procedure, Endovascular procedures, Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Image Interpretation, Computer-Assisted::Tomography, X-Ray Computed::Computed Tomography Angiography [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], cardiovascular system, Radiology, Nuclear Medicine and imaging, Abdominal, Stents, Angiografia, cardiovascular diseases, Computed tomography angiography, Other subheadings::Other subheadings::/diagnostic imaging [Other subheadings], Educational Review, Aneurisma abdominal - Imatgeria
Abstract

Aortic aneurysm; Blood vessel prosthesis implantation; Endovascular procedures Aneurisma aórtico; Implantación de prótesis de vasos sanguíneos; Procedimientos endovasculares Aneurisma aòrtic; Implantació de pròtesis de vasos sanguinis; Procediments endovasculars Endovascular aneurysm repair (EVAR) is a minimally invasive treatment proposed as an alternative to open repair in patients with abdominal aortic aneurysms. EVAR consists in a stent-graft placement within the aorta in order to exclude the aneurysm from arterial circulation and reduce the risk of rupture. Knowledge of the various types of devices is mandatory because some stents/grafts are more frequently associated with complications. CT angiography is the gold standard diagnostic technique for preprocedural planning and postprocedural surveillance. EVAR needs long-term follow-up due to the high rate of complications. Complications can be divided in endograft device-related and systemic complications. The purpose of this article is to review the CT imaging findings of EVAR complications and the key features for the diagnosis.

Published
2022

44. CT imaging findings of abdominopelvic vascular compression syndromes: what the radiologist needs to know

Author

Dario Picone, Giovanni Caruana, Agita Jukna, Massimo Midiri, Giuseppe Salvaggio, Dario Giambelluca, Roberto Cannella, Cecilia Gozzo, Gozzo C., Giambelluca D., Cannella R., Caruana G., Jukna A., Picone D., Midiri M., and Salvaggio G.

Subjects
lcsh:Medical physics. Medical radiology. Nuclear medicine, medicine.medical_specialty, Vascular syndromes, lcsh:R895-920, Asymptomatic, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Nutcracker syndrome, 0302 clinical medicine, Abdomen, medicine, Radiology, Nuclear Medicine and imaging, Vascular compression syndrome, Computed tomography, Neuroradiology, Educational Review, medicine.diagnostic_test, business.industry, Interventional radiology, medicine.disease, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Radiology, medicine.symptom, Presentation (obstetrics), business, Median arcuate ligament syndrome, Superior mesenteric artery syndrome
Abstract

Abdominopelvic vascular compression syndromes include a variety of uncommon conditions characterized by either extrinsic compression of blood vessels by adjacent anatomical structures (i.e., median arcuate ligament syndrome, nutcracker syndrome, May-Thurner syndrome) or compression of hollow viscera by adjacent vessels (i.e., superior mesenteric artery syndrome, ureteropelvic junction obstruction, ureteral vascular compression syndromes, portal biliopathy). These syndromes can be unexpectedly diagnosed even in asymptomatic patients and the predisposing anatomic conditions can be incidentally discovered on imaging examinations performed for other indications, or they can manifest with atypical abdominal symptoms and acute complications, which may lead to significant morbidity if unrecognized. Although computed tomography (CT) is an accurate noninvasive technique for their detection, the diagnosis remains challenging due to the uncommon clinical presentation and often overlooked imaging features. Dynamic imaging may be performed in order to evaluate patients with inconstant symptoms manifesting in a specific position. The purposes of this paper are to review the CT imaging findings of abdominopelvic vascular compression syndromes, correlating with anatomical variants and to provide key features for the noninvasive imaging diagnosis.

Published
2019

45. Coronary endarterectomy to facilitate bypass surgery for patients with extensive stenting of the left anterior descending artery

Author

Claudia Calia, Giovanni Caruana, Maria R. Re, Emanuele Lentini, Caterina Giardina, Cesira Palmeri di Villalba, Sara Rita Vacirca, Gianfranco Filippone, Vincenzo Argano, Filippone G., Calia C., Vacirca S.R., Caruana G., Re M.R., Giardina C., Lentini E., Palmeri Di Villalba C., and Argano V.

Subjects
Male, medicine.medical_specialty, Coronary endarterectomy, medicine.medical_treatment, Endarterectomy, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Text mining, Device removal, Medicine, Humans, Coronary Artery Bypass, Device Removal, Images in CAD, business.industry, General Medicine, Middle Aged, Coronary Vessels, Surgery, medicine.anatomical_structure, 030228 respiratory system, Bypass surgery, Stents, Cardiology and Cardiovascular Medicine, business, Artery
Abstract

A 52-year-old male. Admitted for acute coronary syndrome because of three-vessel disease with a FMJ–LAD

Published
2018

47. Does Transfer Capacitive Resistive Energy Has a Therapeutic Effect on Peyronie's Disease? Randomized, Single-Blind, Sham-Controlled Study on 96 Patients: Fast Pain Relief

Author

Carlo Pavone, Salvatore Romeo, Francesco D'Amato, Manuela Usala, Giulia Letizia Mauro, Giovanni Caruana, Pavone, C., Romeo, S., D'Amato, F., Usala, M., LETIZIA MAURO, G., and Caruana, G.

Subjects
Male, medicine.medical_specialty, Time Factors, Visual analogue scale, Peyronie's disease, Urology, Penile Induration, 030232 urology & nephrology, Pain relief, Pain, Electric Stimulation Therapy, Electric Capacitance, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Electric Impedance, Medicine, Humans, Single-Blind Method, Adverse effect, Penile pain, Aged, Pain Measurement, Resistive touchscreen, Erectile failure, Induratio penis plastic, Penis plaque, Transfer capacitive resistive energy, 030219 obstetrics & reproductive medicine, business.industry, Settore MED/34 - Medicina Fisica E Riabilitativa, Penile Erection, Therapeutic effect, Recovery of Function, Middle Aged, medicine.disease, Treatment Outcome, Tolerability, Italy, Physical therapy, business, Penis
Abstract

Background/Aims/Objectives: We have investigated the clinical and physiological effects of Transfer Capacitive Resistive Energy (TCARE) therapy on men with Peyronie's disease (PD). Methods: Ninety-six men with PD have been randomized in a 2:1 ratio to receive 3 sessions of TCARE therapy or sham therapy. Pain, penile curvature and erectile function have been assessed before the first treatment and up to 9 months after the end of treatment, using the Visual Analogue Scale for the pain, a goniometer to measure the degree of curvature using at-home photography and an International Index of Erectile Function (IIEF-5) questionnaire. Results: A significant pain reduction at the end of the treatment in 51 (79.6%) patients (p < 0.01) of the treated group was observed. No significant improvements in the sham group (p = 0.23) have been observed. No statistical differences in the degree of curvature have been observed in both groups. No statistical improvements have been observed in the IIEF-5 questionnaire. Adverse events have not been reported. Conclusion: This is, to our knowledge, the first randomized, single-blind, sham-controlled study that shows that TCARE has a positive short-term clinical effect on pain in patients with PD. The feasibility and tolerability of this treatment produce an attractive new therapeutic option for men with PD.

Published
2016

48. Cytokine gene expression in the tunica albuginea in patients with Peyronie's disease. Pilot study with a control group

Author

PAVONE, Carlo, CARUANA, Giovanni, ABBADESSA, Daniela, Usala, M, SCADUTO, Giovanna, COLOMBA, Paolo, ALESSANDRO, Riccardo, Pavone, C, Caruana, G, Abbadessa, D, Usala, M, Scaduto, G, Colomba, P, and Alessandro, R

Subjects
Settore BIO/13 - Biologia Applicata, Malattia di La Peyronie, CITOCHINE, Settore MED/24 - Urologia
Abstract

INTRODUZIONE: Abbiamo pensato di effettuare uno studio che indagasse circa la presenza delle citochine nell’albuginea di soggetti affetti da malattia di La Peyronie. Le citochine, in quanto responsabili della comunicazione intercellulare, potrebbero essere coinvolte nella patogenesi della malattia. L’individuazione di una o più citochine responsabili potrebbe, infatti, risultare utile nel trattamento farmacologico grazie ai c.d. farmaci biologici, in grado di interferire con le citochine. MATERIALI E METODI: Per lo studio sono stati reclutati tra gennaio 2009 e dicembre 2010 presso l’Ambulatorio di Chirurgia Andrologica del Policlinico di Palermo 20 soggetti affetti da malattia di La Peyronie (fig. 1) e 8 soggetti affetti da recurvatum penis congenito, questi ultimi adoperati come controllo. Come criteri di inclusione allo studio abbiamo considerato i criteri di operabilità con corporoplastica secondo Nesbit. I prelievi bioptici ottenuti dalle losanghe escisse in corso di intervento chirurgico sono stati utilizzati per saggiare l’espressione genica, attraverso Real-Time PCR, di citochine pro-fibrotiche e pro-infiammatorie. Inoltre sono stati sottoposti dopo fissazione ad esame istologico con la colorazione ematossilina-eosina. RISULTATI E DISCUSSIONE: L’esame istologico ha rilevato l’assenza di cellule infiammatorie in tutti i pazienti recensiti per lo studio. L’analisi dell’espressione dei geni codificanti per IL-4 (Interleuchina-4), IL-6 (Interleuchina-6), IL-13 (Interleuchina-13), TGF-β1 (Trasforming Growth Factor - β1), IL-2 (Interleuchina-2), IL-10 (Interleuchina-10), TNF-α (Tumor Necrosis Factor- α) e IFN-γ (Interferone- γ) ha evidenziato in tutti i campioni un livello molto basso di trascritti e in alcuni casi indosabili (fig. 2). Inoltre i livelli dei trascritti delle citochine prese in esame sono risultati minori nei campioni provenienti dagli individui affetti da malattia di La Peyronie rispetto ai controlli. CONCLUSIONI: Alla luce dei risultati ottenuti, l’utilizzo di farmaci biologici (anticorpi) contro le citochine non sembra essere applicabile nella fase stabile della malattia di La Peyronie

Published
2015

49. Compliance to therapy with Dapoxetine in comparison to a conventional selective serotonin reuptake inhibitor (Citalopram) in 118 patients with premature ejaculation

Author

PAVONE, Carlo, ABBADESSA, Daniela, SCADUTO, Giovanna, CARUANA, Giovanni, GAMBINO, Giuseppa, SERRETTA, Vincenzo, SCALICI GESOLFO, Cristina, Pavone, C, Abbadessa, D, Scaduto, G, Caruana, G, Gambino, G, Serretta, V, and Scalici Gesolfo, C

Subjects
Dapoxetine, SSRI, Premaure Ejaculation, compliance, Settore MED/24 - Urologia
Abstract

Premature Ejaculation (PE) is a sexual dysfunction that concern 20-30% of the male population. Dapoxetine is a new serotonine re-uptake inhibitor (SSRI)specific for PE treatment.Aim of the study is to assess compliance and effectiveness of the treatment with dapoxetine compared to the treatment with citalopram (a classic SSRI used to treat PE).

Published
2013

50. Does Exist A Correlation Between BMI and Gleason Patterns 4 and 5 At Prostate Biopsy?

Author

Giuseppe Cicero, Giovanni Caruana, Giuseppe Carità, Vito Franco, Federico Torretta, Francesco Sommatino, Vincenzo Serretta, M. Daricello, Luigi Vaccarella, Salvatore Scurria, Serretta,V, Caruana, G, Sommatino, F, Scurria, S, Carità, G, Vaccarella,L, Torretta, F, Cicero, G, Daricello, M, and Franco, V

Subjects
Gleason grade, Oncology, Biochemical recurrence, medicine.medical_specialty, Prostate cancer, Prostate biopsy, medicine.diagnostic_test, business.industry, Urology, urologic and male genital diseases, medicine.disease, Settore MED/24 - Urologia, Correlation, BMI, Prostate Biopsy, Internal medicine, Biopsy, medicine, Malignant cells, Obesity, business, Body mass index
Abstract

Background: Obesity has been related with higher Gleason grade and worse prognosis. Increasing proportion of Gleason pattern 4 or 5 is a critical factor for biochemical recurrence, progression and mortality. The endocrine activity of visceral fat could be responsible of the differentation of the prostatic malignant cell towards a more aggressive fenotype. The aim of our study was to correlate Body Mass Index with the presence of Gleason pattern 4 or higher at biopsy. Materials and Methods: Consecutive patients with positive prostate biopsy were included. A transrectal prostate biopsy procedure with 12 cores, was performed. All tissue samples were reviewed. Results: Out of 135 patients diagnosed with prostate cancer at biopsy, a Gleason. pattern 4 or 5 was evident in 57 (42%) patients, while it was not detected in 78 (58%). The statistical analysis did not demonstrate a correlation between the histological expression of Gleason pattern 4 or 5 in the bioptic specimens and the BMI class. Conclusion: Although high risk prostate cancer has been reported more frequent in patients with higher BMI, in our experience, no significant correlation between BMI and Gleason patterns 4 and 5 at biopsy was detected. Other factors responsible for the worse prognosis and the more aggressive behavior of prostate tumors in obeses should be investigated.

Published
2013

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