Search

Your search keyword '"Tomchaney, M."' showing total 17 results
Start Over Author "Tomchaney, M."
17 results on '"Tomchaney, M."'

2. Comorbidities, cardiovascular therapies, and COVID-19 mortality: A nationwide, italian observational study (ItaliCO)

Author

Polverino, F, Stern, D, Ruocco, G, Balestro, E, Bassetti, M, Candelli, M, Cirillo, B, Contoli, M, Corsico, A, D'Amico, F, D'Elia, E, Falco, G, Gasparini, S, Guerra, S, Harari, S, Kraft, M, Mennella, L, Papi, A, Parrella, R, Pelosi, P, Poletti, V, Polverino, M, Tana, C, Terribile, R, Woods, J, Di Marco, F, Martinez, F, Zhang, S, Geelhoed, B, Sinning, C, Agarossi, A, Agati, S, Agosteo, E, Ando', F, Andreoni, M, Angelillo, I, Arcoleo, G, Arena, C, Baiamonte, P, Ball, L, Banfi, P, Bartoletti, G, Bartolotta, R, Battaglini, D, Bellan, M, Benzoni, I, Bertolini, R, Bevilacqua, M, Bezzi, M, Bianco, A, Bisbano, A, Bobbio, F, Bocchialini, G, Bonetti, F, Boni, F, Bonifazi, M, Borgonovo, G, Borre', S, Bosio, M, Brachini, G, Brunetti, I, Calagna, L, Calo, F, Capuozzo, A, Carr, T, Castellani, A, Catalano, F, Catania, G, Catena, E, Cattaneo, M, Cattelan, A, Ceruti, V, Chiumiento, F, Cicchitto, G, Confalonieri, M, Confalonieri, P, Coppola, N, Cosentina, R, Costantino, R, Crimi, C, Curra, A, D'Abbraccio, M, Dalbeni, A, Daleffe, F, Davide, R, Del Donno, M, Di Pastena, F, Di Perna, F, Di Rosa, Z, Di Sabatino, A, Elesbani, O, Elia, D, Esposito, V, Fabiani, L, Falo, G, Fanelli, C, Fantin, A, Ferrigno, F, Fiorentino, G, Franceschi, F, Fronza, M, Gardenghi, G, Giacobbe, D, Giannotti, C, Giannotti, G, Gidari, A, Giovanardi, F, Gnerre, P, Gonnelli, F, Graziano, M, Greco, S, Grosso, A, Guarino, S, Iannarelli, A, Imitazione, P, Inglese, F, Iodice, V, Izzo, A, La Greca, C, Lax, A, Legittimo, F, Leo, A, Leone, S, Lepidini, V, Leto, M, Licata, F, Locati, F, Lorini, L, Lucchetti, B, Maida, I, Macera, M, Manzillo, E, March, A, Mascheroni, D, Mastroianni, A, Mauro, I, Mazzitelli, M, Mazzuca, E, Micheletto, C, Mingoli, A, Minuz, P, Moioli, M, Monti, L, Morgagni, R, Mucci, L, Muselli, M, Negri, S, Nobile, C, Oldani, S, Olivieri, C, Parati, G, Parodi, L, Pastorelli, E, Patruno, V, Pellegrino, F, Pengo, M, Pepe, D, Perotti, A, Petrino, R, Petrucci, M, Piane, R, Pignataro, G, Pino, M, Pirisi, M, Porru, F, Pugliese, F, Punzi, R, Ramaroli, D, Robba, C, Rostagno, R, Sabatini, U, Sainaghi, P, Salton, F, Salzano, C, Sanduzzi, A, Zamparelli, S, Sangiovanni, V, Santopuoli, D, Sapienza, P, Sarmati, L, Schiaroli, E, Scienza, F, Senni, M, Serchisu, L, Sgherzi, S, Soddu, D, Soranna, D, Sorino, C, Spadaro, S, Stirpe, E, Tardivo, S, Tartaglia, S, Teopompi, E, Tomchaney, M, Torelli, E, Torlasco, C, Torti, C, Tupputi, E, Ugolinelli, C, Vatrella, A, Versace, A, Villani, M, Vincenzo, L, Volta, C, Voraphani, N, Zekaj, E, Zoppellari, R, Polverino F., Stern D. A., Ruocco G., Balestro E., Bassetti M., Candelli M., Cirillo B., Contoli M., Corsico A., D'Amico F., D'Elia E., Falco G., Gasparini S., Guerra S., Harari S., Kraft M., Mennella L., Papi A., Parrella R., Pelosi P., Poletti V., Polverino M., Tana C., Terribile R., Woods J. C., Di Marco F., Martinez F. D., Zhang S., Geelhoed B., Sinning C., Agarossi A., Agati S., Agosteo E., Ando' F., Andreoni M., Angelillo I. F., Arcoleo G., Arena C., Baiamonte P., Ball L., Banfi P., Bartoletti G., Bartolotta R., Battaglini D., Bellan M., Benzoni I., Bertolini R., Bevilacqua M., Bezzi M., Bianco A., Bisbano A., Bobbio F., Bocchialini G., Bonetti F., Boni F., Bonifazi M., Borgonovo G., Borre' S., Bosio M., Brachini G., Brunetti I., Calagna L., Calo F., Capuozzo A., Carr T., Castellani A., Catalano F., Catania G., Catena E., Cattaneo M., Cattelan A., Ceruti V., Chiumiento F., Cicchitto G., Confalonieri M., Confalonieri P., Coppola N., Cosentina R., Costantino R., Crimi C., Curra A., D'Abbraccio M., Dalbeni A., Daleffe F., Davide R., Del Donno M., Di Pastena F., Di Perna F., Di Rosa Z., Di Sabatino A., Elesbani O., Elia D., Esposito V., Fabiani L., Falo G., Fanelli C., Fantin A., Ferrigno F., Fiorentino G., Franceschi F., Fronza M., Gardenghi G. G., Giacobbe D. R., Giannotti C., Giannotti G., Gidari A., Giovanardi F., Gnerre P., Gonnelli F., Graziano M., Greco S., Grosso A., Guarino S., Iannarelli A., Imitazione P., Inglese F., Iodice V., Izzo A., La Greca C., Lax A., Legittimo F., Leo A., Leone S., Lepidini V., Leto M., Licata F., Locati F., Lorini L., Lucchetti B., Maida I., Macera M., Manzillo E., March A., Mascheroni D., Mastroianni A., Mauro I., Mazzitelli M., Mazzuca E., Micheletto C., Mingoli A., Minuz P., Moioli M., Monti L., Morgagni R., Mucci L., Muselli M., Negri S., Nobile C. G. A., Oldani S., Olivieri C., Parati G., Parodi L., Pastorelli E., Patruno V., Pellegrino F., Pengo M. F., Pepe D., Perotti A., Petrino R., Petrucci M., Piane R. M., Pignataro G., Pino M., Pirisi M., Porru F., Pugliese F., Punzi R., Ramaroli D. A., Robba C., Rostagno R., Sabatini U., Sainaghi P. P., Salton F., Salzano C., Sanduzzi A., Zamparelli S. S., Sangiovanni V., Santopuoli D., Sapienza P., Sarmati L., Schiaroli E., Scienza F., Senni M., Serchisu L., Sgherzi S., Soddu D., Soranna D., Sorino C., Spadaro S., Stirpe E., Tardivo S., Tartaglia S., Teopompi E., Tomchaney M., Torelli E., Torlasco C., Torti C., Tupputi E., Ugolinelli C., Vatrella A., Versace A. G., Villani M., Vincenzo L., Volta C. A., Voraphani N., Zekaj E., Zoppellari R., Polverino, F, Stern, D, Ruocco, G, Balestro, E, Bassetti, M, Candelli, M, Cirillo, B, Contoli, M, Corsico, A, D'Amico, F, D'Elia, E, Falco, G, Gasparini, S, Guerra, S, Harari, S, Kraft, M, Mennella, L, Papi, A, Parrella, R, Pelosi, P, Poletti, V, Polverino, M, Tana, C, Terribile, R, Woods, J, Di Marco, F, Martinez, F, Zhang, S, Geelhoed, B, Sinning, C, Agarossi, A, Agati, S, Agosteo, E, Ando', F, Andreoni, M, Angelillo, I, Arcoleo, G, Arena, C, Baiamonte, P, Ball, L, Banfi, P, Bartoletti, G, Bartolotta, R, Battaglini, D, Bellan, M, Benzoni, I, Bertolini, R, Bevilacqua, M, Bezzi, M, Bianco, A, Bisbano, A, Bobbio, F, Bocchialini, G, Bonetti, F, Boni, F, Bonifazi, M, Borgonovo, G, Borre', S, Bosio, M, Brachini, G, Brunetti, I, Calagna, L, Calo, F, Capuozzo, A, Carr, T, Castellani, A, Catalano, F, Catania, G, Catena, E, Cattaneo, M, Cattelan, A, Ceruti, V, Chiumiento, F, Cicchitto, G, Confalonieri, M, Confalonieri, P, Coppola, N, Cosentina, R, Costantino, R, Crimi, C, Curra, A, D'Abbraccio, M, Dalbeni, A, Daleffe, F, Davide, R, Del Donno, M, Di Pastena, F, Di Perna, F, Di Rosa, Z, Di Sabatino, A, Elesbani, O, Elia, D, Esposito, V, Fabiani, L, Falo, G, Fanelli, C, Fantin, A, Ferrigno, F, Fiorentino, G, Franceschi, F, Fronza, M, Gardenghi, G, Giacobbe, D, Giannotti, C, Giannotti, G, Gidari, A, Giovanardi, F, Gnerre, P, Gonnelli, F, Graziano, M, Greco, S, Grosso, A, Guarino, S, Iannarelli, A, Imitazione, P, Inglese, F, Iodice, V, Izzo, A, La Greca, C, Lax, A, Legittimo, F, Leo, A, Leone, S, Lepidini, V, Leto, M, Licata, F, Locati, F, Lorini, L, Lucchetti, B, Maida, I, Macera, M, Manzillo, E, March, A, Mascheroni, D, Mastroianni, A, Mauro, I, Mazzitelli, M, Mazzuca, E, Micheletto, C, Mingoli, A, Minuz, P, Moioli, M, Monti, L, Morgagni, R, Mucci, L, Muselli, M, Negri, S, Nobile, C, Oldani, S, Olivieri, C, Parati, G, Parodi, L, Pastorelli, E, Patruno, V, Pellegrino, F, Pengo, M, Pepe, D, Perotti, A, Petrino, R, Petrucci, M, Piane, R, Pignataro, G, Pino, M, Pirisi, M, Porru, F, Pugliese, F, Punzi, R, Ramaroli, D, Robba, C, Rostagno, R, Sabatini, U, Sainaghi, P, Salton, F, Salzano, C, Sanduzzi, A, Zamparelli, S, Sangiovanni, V, Santopuoli, D, Sapienza, P, Sarmati, L, Schiaroli, E, Scienza, F, Senni, M, Serchisu, L, Sgherzi, S, Soddu, D, Soranna, D, Sorino, C, Spadaro, S, Stirpe, E, Tardivo, S, Tartaglia, S, Teopompi, E, Tomchaney, M, Torelli, E, Torlasco, C, Torti, C, Tupputi, E, Ugolinelli, C, Vatrella, A, Versace, A, Villani, M, Vincenzo, L, Volta, C, Voraphani, N, Zekaj, E, Zoppellari, R, Polverino F., Stern D. A., Ruocco G., Balestro E., Bassetti M., Candelli M., Cirillo B., Contoli M., Corsico A., D'Amico F., D'Elia E., Falco G., Gasparini S., Guerra S., Harari S., Kraft M., Mennella L., Papi A., Parrella R., Pelosi P., Poletti V., Polverino M., Tana C., Terribile R., Woods J. C., Di Marco F., Martinez F. D., Zhang S., Geelhoed B., Sinning C., Agarossi A., Agati S., Agosteo E., Ando' F., Andreoni M., Angelillo I. F., Arcoleo G., Arena C., Baiamonte P., Ball L., Banfi P., Bartoletti G., Bartolotta R., Battaglini D., Bellan M., Benzoni I., Bertolini R., Bevilacqua M., Bezzi M., Bianco A., Bisbano A., Bobbio F., Bocchialini G., Bonetti F., Boni F., Bonifazi M., Borgonovo G., Borre' S., Bosio M., Brachini G., Brunetti I., Calagna L., Calo F., Capuozzo A., Carr T., Castellani A., Catalano F., Catania G., Catena E., Cattaneo M., Cattelan A., Ceruti V., Chiumiento F., Cicchitto G., Confalonieri M., Confalonieri P., Coppola N., Cosentina R., Costantino R., Crimi C., Curra A., D'Abbraccio M., Dalbeni A., Daleffe F., Davide R., Del Donno M., Di Pastena F., Di Perna F., Di Rosa Z., Di Sabatino A., Elesbani O., Elia D., Esposito V., Fabiani L., Falo G., Fanelli C., Fantin A., Ferrigno F., Fiorentino G., Franceschi F., Fronza M., Gardenghi G. G., Giacobbe D. R., Giannotti C., Giannotti G., Gidari A., Giovanardi F., Gnerre P., Gonnelli F., Graziano M., Greco S., Grosso A., Guarino S., Iannarelli A., Imitazione P., Inglese F., Iodice V., Izzo A., La Greca C., Lax A., Legittimo F., Leo A., Leone S., Lepidini V., Leto M., Licata F., Locati F., Lorini L., Lucchetti B., Maida I., Macera M., Manzillo E., March A., Mascheroni D., Mastroianni A., Mauro I., Mazzitelli M., Mazzuca E., Micheletto C., Mingoli A., Minuz P., Moioli M., Monti L., Morgagni R., Mucci L., Muselli M., Negri S., Nobile C. G. A., Oldani S., Olivieri C., Parati G., Parodi L., Pastorelli E., Patruno V., Pellegrino F., Pengo M. F., Pepe D., Perotti A., Petrino R., Petrucci M., Piane R. M., Pignataro G., Pino M., Pirisi M., Porru F., Pugliese F., Punzi R., Ramaroli D. A., Robba C., Rostagno R., Sabatini U., Sainaghi P. P., Salton F., Salzano C., Sanduzzi A., Zamparelli S. S., Sangiovanni V., Santopuoli D., Sapienza P., Sarmati L., Schiaroli E., Scienza F., Senni M., Serchisu L., Sgherzi S., Soddu D., Soranna D., Sorino C., Spadaro S., Stirpe E., Tardivo S., Tartaglia S., Teopompi E., Tomchaney M., Torelli E., Torlasco C., Torti C., Tupputi E., Ugolinelli C., Vatrella A., Versace A. G., Villani M., Vincenzo L., Volta C. A., Voraphani N., Zekaj E., and Zoppellari R.

Abstract

Background: Italy has one of the world’s oldest populations, and suffered one the highest death tolls from Coronavirus disease 2019 (COVID-19) worldwide. Older people with cardiovascular diseases (CVDs), and in particular hypertension, are at higher risk of hospitalization and death for COVID-19. Whether hypertensionmedicationsmay increase the risk for death in older COVID 19 inpatients at the highest risk for the disease is currently unknown. Methods: Data from 5,625 COVID-19 inpatients were manually extracted from medical charts from 61 hospitals across Italy. From the initial 5,625 patients, 3,179 were included in the study as they were either discharged or deceased at the time of the data analysis. Primary outcome was inpatient death or recovery. Mixed effects logistic regression models were adjusted for sex, age, and number of comorbidities, with a random effect for site. Results: A large proportion of participating inpatients were ≥65 years old (58%), male (68%), non-smokers (93%) with comorbidities (66%). Each additional comorbidity increased the risk of death by 35% [adjOR = 1.35 (1.2, 1.5) p < 0.001]. Use of ACE inhibitors, ARBs, beta-blockers or Ca-antagonists was not associated with significantly increased risk of death. There was a marginal negative association between ARB use and death, and a marginal positive association between diuretic use and death. Conclusions: This Italian nationwide observational study of COVID-19 inpatients, the majority of which ≥65 years old, indicates that there is a linear direct relationship between the number of comorbidities and the risk of death. Among CVDs, hypertension and pre-existing cardiomyopathy were significantly associated with risk of death. The use of hypertension medications reported to be safe in younger cohorts, do not contribute significantly to increased COVID-19 related deaths in an older population that suffered one of the highest death tolls worldwide.

Published
2020

3. Comorbidities, cardiovascular therapies, and COVID-19 mortality: A nationwide, italian observational study (ItaliCO)

Author

Polverino, F., Phd, Md, Stern, D., Polverino, M., D'Amico, F., D'Elia, E., Agarossi, A., Agati, S., Agosteo, E., Ando', F., Andreoni, M., Angelillo, If., Dds, Mph, Arcoleo, G., Arena, C., Baiamonte, P., Balestro, E., Ball, L., Banfi, P., Bartoletti, G., Bartolotta, R., Bassetti, M., Battaglini, D., Bellan, M., Benzoni, I., Bertolini, R., Bevilacqua, M., Bezzi, M., Bianco, A., Bisbano, A., Bobbio, F., Bocchialini, G., Bonetti, F., Boni, F., Bonifazi, M., Borgonovo, G., Borre', S., Bosio, M., Brachini, G., Brunetti, I., Calagna, L., Calò, F., Candelli, M., Capuozzo, A., Carr, T., Castellani, A., Catalano, F., Catania, G., Catena, E., Cattaneo, M., Cattelan, A., Ceruti, V., Chiumiento, F., Cicchitto, G., Cirillo, B., Confalonieri, M., Confalonieri, P., Contoli, M., Coppola, N., Corsico, A., Cosentina, R., Costantino, R., Crimi, C., Currà, A., D'Abbraccio, M., Dalbeni, A., Daleffe, F., Davide, R., Del Donno, M., Di Marco, F., Di Pastena, F., Di Perna, F., Di Rosa, Z., Di Sabatino, A., Elesbani, O., Elia, D., Esposito, V., Fabiani, L., Falco, G., Falo, G., Fanelli, C., Fantin, A., Ferrigno, F., Fiorentino, G., Franceschi, F., Fronza, M., Gardini Gardenghi, G., Gasparini, S., Giacobbe, D. R., Giannotti, C., Giannotti, G., Gidari, A., Giovanardi, F., Gnerre, P., Gonnelli, F., Graziano, M., Greco, S., Grosso, A., Phd, Guarino, S., Guerra, S., Harari, S., Iannarelli, A., Imitazione, P., Inglese, F., Iodice, V., Izzo, A., La Greca, C., Kraft, M., Lax, A., Legittimo, F., Leo, A., Leone, S., Lepidini, V., Leto, M., Licata, F., Locati, F., Lorini, L., Lucchetti, B., Maida, I., Macera, M., Manzillo, E., March, A., Mascheroni, D., Mastroianni, A., Mauro, I., Mazzitelli, M., Mazzuca, E., Mennella, L., Micheletto, C., Mingoli, A., Minuz, P., Moioli, M., Monti, L., Morgagni, R., Mucci, L., Muselli, M., Negri, S., Nobile, C. G. A., Oldani, S., Olivieri, C., Papi, A., Parati, G., Parodi, L., Parrella, R., Pastorelli, E., Patruno, V., Pellegrino, F., Pelosi, P., Fers, Md, Pengo, M. F., Pepe, D., Perotti, A., Petrino, R., Petrucci, M., Piane, R. M., Pignataro, G., Pino, M., Pirisi, M., Poletti, V., Porru, F., Pugliese, F., Punzi, R., Ramaroli, D. A., Robba, C., Rostagno, R., Ruocco, G., Sabatini, U., Sainaghi, P. P., Salton, F., Salzano, C., Sanduzzi, A., Sanduzzi Zamparelli, S., Sangiovanni, V., Santopuoli, D., Sapienza, P., Sarmati, L., Schiaroli, E., Scienza, F., Senni, M., Serchisu, L., Sgherzi, S., Soddu, D., Soranna, D., Sorino, C., Spadaro, S., Stirpe, E., Tana, C., Tardivo, S., Tartaglia, S., Teopompi, E., Terribile, R., Tomchaney, M., Torelli, E., Torlasco, C., Torti, C., Tupputi, E., Ugolinelli, C., Vatrella, A., Versace, A. G., Villani, M., Vincenzo, L., Volta, C. A., Voraphani, N., Woods, J. C., Zekaj, E., Zoppellari, R., Martinez, and F. D., Polverino, Francesca, Stern, Debra A, Ruocco, Gaetano, Balestro, Elisabetta, Bassetti, Matteo, Candelli, Marcello, Cirillo, Bruno, Contoli, Marco, Corsico, Angelo, D'Amico, Filippo, D'Elia, Emilia, Falco, Giuseppe, Gasparini, Stefano, Guerra, Stefano, Harari, Sergio, Kraft, Monica, Mennella, Luigi, Papi, Alberto, Parrella, Roberto, Pelosi, Paolo, Poletti, Venerino, Polverino, Mario, Tana, Claudio, Terribile, Roberta, Woods, Jason C, Di Marco, Fabiano, Martinez, Fernando D, Angelillo, Italo Francesco, Stern, Debra A., C Woods, Jason, Martinez, Fernando D., Polverino, F., Stern, D., Polverino, M., D'Amico, F., D'Elia, E., Agarossi, A., Agati, S., Agosteo, E., Ando', F., Andreoni, M., Angelillo, If., Arcoleo, G., Arena, C., Baiamonte, P., Balestro, E., Ball, L., Banfi, P., Bartoletti, G., Bartolotta, R., Bassetti, M., Battaglini, D., Bellan, M., Benzoni, I., Bertolini, R., Bevilacqua, M., Bezzi, M., Bianco, A., Bisbano, A., Bobbio, F., Bocchialini, G., Bonetti, F., Boni, F., Bonifazi, M., Borgonovo, G., Borre', S., Bosio, M., Brachini, G., Brunetti, I., Calagna, L., Calò, F., Candelli, M., Capuozzo, A., Carr, T., Castellani, A., Catalano, F., Catania, G., Catena, E., Cattaneo, M., Cattelan, A., Ceruti, V., Chiumiento, F., Cicchitto, G., Cirillo, B., Confalonieri, M., Confalonieri, P., Contoli, M., Coppola, N., Corsico, A., Cosentina, R., Costantino, R., Crimi, C., Currà, A., D'Abbraccio, M., Dalbeni, A., Daleffe, F., Davide, R., Del Donno, M., Di Marco, F., Di Pastena, F., Di Perna, F., Di Rosa, Z., Di Sabatino, A., Elesbani, O., Elia, D., Esposito, V., Fabiani, L., Falco, G., Falo, G., Fanelli, C., Fantin, A., Ferrigno, F., Fiorentino, G., Franceschi, F., Fronza, M., Gardini Gardenghi, G., Gasparini, S., Giacobbe, D. R., Giannotti, C., Giannotti, G., Gidari, A., Giovanardi, F., Gnerre, P., Gonnelli, F., Graziano, M., Greco, S., Grosso, A., Guarino, S., Guerra, S., Harari, S., Iannarelli, A., Imitazione, P., Inglese, F., Iodice, V., Izzo, A., La Greca, C., Kraft, M., Lax, A., Legittimo, F., Leo, A., Leone, S., Lepidini, V., Leto, M., Licata, F., Locati, F., Lorini, L., Lucchetti, B., Maida, I., Macera, M., Manzillo, E., March, A., Mascheroni, D., Mastroianni, A., Mauro, I., Mazzitelli, M., Mazzuca, E., Mennella, L., Micheletto, C., Mingoli, A., Minuz, P., Moioli, M., Monti, L., Morgagni, R., Mucci, L., Muselli, M., Negri, S., Nobile, C. G. A., Oldani, S., Olivieri, C., Papi, A., Parati, G., Parodi, L., Parrella, R., Pastorelli, E., Patruno, V., Pellegrino, F., Pelosi, P., Pengo, M. F., Pepe, D., Perotti, A., Petrino, R., Petrucci, M., Piane, R. M., Pignataro, G., Pino, M., Pirisi, M., Poletti, V., Porru, F., Pugliese, F., Punzi, R., Ramaroli, D. A., Robba, C., Rostagno, R., Ruocco, G., Sabatini, U., Sainaghi, P. P., Salton, F., Salzano, C., Sanduzzi, A., Sanduzzi Zamparelli, S., Sangiovanni, V., Santopuoli, D., Sapienza, P., Sarmati, L., Schiaroli, E., Scienza, F., Senni, M., Serchisu, L., Sgherzi, S., Soddu, D., Soranna, D., Sorino, C., Spadaro, S., Stirpe, E., Tana, C., Tardivo, S., Tartaglia, S., Teopompi, E., Terribile, R., Tomchaney, M., Torelli, E., Torlasco, C., Torti, C., Tupputi, E., Ugolinelli, C., Vatrella, A., Versace, A. G., Villani, M., Vincenzo, L., Volta, C. A., Voraphani, N., Woods, J. C., Zekaj, E., Zoppellari, R., Martinez, F. D., Public Health, Polverino, F, Stern, D, Ruocco, G, Balestro, E, Bassetti, M, Candelli, M, Cirillo, B, Contoli, M, Corsico, A, D'Amico, F, D'Elia, E, Falco, G, Gasparini, S, Guerra, S, Harari, S, Kraft, M, Mennella, L, Papi, A, Parrella, R, Pelosi, P, Poletti, V, Polverino, M, Tana, C, Terribile, R, Woods, J, Di Marco, F, Martinez, F, Zhang, S, Geelhoed, B, Sinning, C, Agarossi, A, Agati, S, Agosteo, E, Ando', F, Andreoni, M, Angelillo, I, Arcoleo, G, Arena, C, Baiamonte, P, Ball, L, Banfi, P, Bartoletti, G, Bartolotta, R, Battaglini, D, Bellan, M, Benzoni, I, Bertolini, R, Bevilacqua, M, Bezzi, M, Bianco, A, Bisbano, A, Bobbio, F, Bocchialini, G, Bonetti, F, Boni, F, Bonifazi, M, Borgonovo, G, Borre', S, Bosio, M, Brachini, G, Brunetti, I, Calagna, L, Calo, F, Capuozzo, A, Carr, T, Castellani, A, Catalano, F, Catania, G, Catena, E, Cattaneo, M, Cattelan, A, Ceruti, V, Chiumiento, F, Cicchitto, G, Confalonieri, M, Confalonieri, P, Coppola, N, Cosentina, R, Costantino, R, Crimi, C, Curra, A, D'Abbraccio, M, Dalbeni, A, Daleffe, F, Davide, R, Del Donno, M, Di Pastena, F, Di Perna, F, Di Rosa, Z, Di Sabatino, A, Elesbani, O, Elia, D, Esposito, V, Fabiani, L, Falo, G, Fanelli, C, Fantin, A, Ferrigno, F, Fiorentino, G, Franceschi, F, Fronza, M, Gardenghi, G, Giacobbe, D, Giannotti, C, Giannotti, G, Gidari, A, Giovanardi, F, Gnerre, P, Gonnelli, F, Graziano, M, Greco, S, Grosso, A, Guarino, S, Iannarelli, A, Imitazione, P, Inglese, F, Iodice, V, Izzo, A, La Greca, C, Lax, A, Legittimo, F, Leo, A, Leone, S, Lepidini, V, Leto, M, Licata, F, Locati, F, Lorini, L, Lucchetti, B, Maida, I, Macera, M, Manzillo, E, March, A, Mascheroni, D, Mastroianni, A, Mauro, I, Mazzitelli, M, Mazzuca, E, Micheletto, C, Mingoli, A, Minuz, P, Moioli, M, Monti, L, Morgagni, R, Mucci, L, Muselli, M, Negri, S, Nobile, C, Oldani, S, Olivieri, C, Parati, G, Parodi, L, Pastorelli, E, Patruno, V, Pellegrino, F, Pengo, M, Pepe, D, Perotti, A, Petrino, R, Petrucci, M, Piane, R, Pignataro, G, Pino, M, Pirisi, M, Porru, F, Pugliese, F, Punzi, R, Ramaroli, D, Robba, C, Rostagno, R, Sabatini, U, Sainaghi, P, Salton, F, Salzano, C, Sanduzzi, A, Zamparelli, S, Sangiovanni, V, Santopuoli, D, Sapienza, P, Sarmati, L, Schiaroli, E, Scienza, F, Senni, M, Serchisu, L, Sgherzi, S, Soddu, D, Soranna, D, Sorino, C, Spadaro, S, Stirpe, E, Tardivo, S, Tartaglia, S, Teopompi, E, Tomchaney, M, Torelli, E, Torlasco, C, Torti, C, Tupputi, E, Ugolinelli, C, Vatrella, A, Versace, A, Villani, M, Vincenzo, L, Volta, C, Voraphani, N, Zekaj, E, and Zoppellari, R

Subjects
0301 basic medicine, COVID-19, comorbidities, ACE inhibitors, mortality, cohort study, medicine.medical_specialty, comorbiditie, lcsh:Diseases of the circulatory (Cardiovascular) system, ACE inhibitors, Coronavirus disease 2019 (COVID-19), COVID-19, cohort study, comorbidities, mortality, Cardiomyopathy, Socio-culturale, Disease, 030204 cardiovascular system & hematology, Cardiovascular Medicine, Logistic regression, Older population, Comorbidities, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Internal medicine, ACE inhibitor, medicine, Mortality, Original Research, business.industry, Cohort study, medicine.disease, Comorbidity, 030104 developmental biology, lcsh:RC666-701, Observational study, Erratum, Cardiology and Cardiovascular Medicine, business
Abstract

Background: Italy has one of the world’s oldest populations, and suffered one the highest death tolls from Coronavirus disease 2019 (COVID-19) worldwide. Older people with cardiovascular diseases (CVDs), and in particular hypertension, are at higher risk of hospitalization and death for COVID-19. Whether hypertensionmedicationsmay increase the risk for death in older COVID 19 inpatients at the highest risk for the disease is currently unknown. Methods: Data from 5,625 COVID-19 inpatients were manually extracted from medical charts from 61 hospitals across Italy. From the initial 5,625 patients, 3,179 were included in the study as they were either discharged or deceased at the time of the data analysis. Primary outcome was inpatient death or recovery. Mixed effects logistic regression models were adjusted for sex, age, and number of comorbidities, with a random effect for site. Results: A large proportion of participating inpatients were ≥65 years old (58%), male (68%), non-smokers (93%) with comorbidities (66%). Each additional comorbidity increased the risk of death by 35% [adjOR = 1.35 (1.2, 1.5) p < 0.001]. Use of ACE inhibitors, ARBs, beta-blockers or Ca-antagonists was not associated with significantly increased risk of death. There was a marginal negative association between ARB use and death, and a marginal positive association between diuretic use and death. Conclusions: This Italian nationwide observational study of COVID-19 inpatients, the majority of which ≥65 years old, indicates that there is a linear direct relationship between the number of comorbidities and the risk of death. Among CVDs, hypertension and pre-existing cardiomyopathy were significantly associated with risk of death. The use of hypertension medications reported to be safe in younger cohorts, do not contribute significantly to increased COVID-19 related deaths in an older population that suffered one of the highest death tolls worldwide.

Published
2020

4. Paradoxical effects of cigarette smoke and COPD on SARS-CoV2 infection and disease

Author

Tomchaney, M., primary, Contoli, M., additional, Mayo, J., additional, Baraldo, S., additional, Shuaizhi, L., additional, Cabel, CR., additional, Bull, DA., additional, Lick, S., additional, Malo, J., additional, Knoper, S., additional, Kim, SS., additional, Tram, J., additional, Rojas-Quintero, J., additional, Kraft, M., additional, Ledford, J., additional, Tesfaigzi, Y., additional, Martinez, F.D., additional, Thorne, C. A., additional, Kheradmand, F., additional, Campos, S. K., additional, Papi, A., additional, and Polverino, F., additional

Published
2020
Full Text
View/download PDF

5. PathogenDx DetectX Combined Demonstrates Equivalent Performance in Comparison to Four AOAC Certified Methods for the Detection of Aspergillus Species, Salmonella Species, and STEC in Dried Hemp Flower.

Author

Katchman BA, Tomchaney M, Rueda A, Stice S, and Hogan M

Subjects
Shiga Toxin, Food Microbiology, Salmonella genetics, Aspergillus genetics, Cannabis, Shiga-Toxigenic Escherichia coli genetics
Abstract

Background: The PathogenDx DetectX Combined method is a certified Performance Tested MethodSM (012201) that is enrichment-free and utilizes a DNA microarray-based end point PCR method for the simultaneous detection of Aspergillus (A. flavus, A. fumigatus, A. niger, and A. terreus), Salmonella spp., and a broad range of Shiga toxin-producing Esherichia coli (STEC) from hemp and cannabis flower, edibles, and concentrates., Objective: This study aimed to compare the PathogenDx DetectX Combined enrichment-free method to four AOAC INTERNATIONAL certified molecular methods that utilize enrichment prior to quantitative PCR (qPCR) amplification in hemp flower for the detection of Aspergillus (A. flavus), S. enterica, and Escherichia coli 026., Methods: In this method comparison study, each method was evaluated according to the AOAC validated instructions for use (IFU) and the AOAC Appendix J validation guidelines. A total of 16 samples at three levels of contamination (0, 0.7, and 2 CFU/10g test portion) were analyzed by each method. The results for all methods were evaluated by using the probability of detection statistical model (POD)., Results: Results of the validation study demonstrate that the PathogenDx DetectX Combined enrichment-free method is equivalent in performance to the three proprietary methods evaluated in this study., Conclusion: The method comparison study indicated that the PathogenDx DetectX Combined enrichment-free method provides equivalent detection of the target analytes (A. flavus, Salmonella, and a broad range of STEC) in hemp flower., Highlights: The performance of The PathogenDx DetectX Combined method is significantly faster and possesses a higher or equivalent degree of sensitivity and specificity. Implementation of this method for routine microbial pathogen analysis in laboratories would save significant time and resources., (© The Author(s) 2023. Published by Oxford University Press on behalf of AOAC INTERNATIONAL.)

Published
2023
Full Text
View/download PDF

6. Independent Study for the Detectx Combined Assay for the Detection of Aspergillus, Salmonella, and STEC (stx1 and/or 2) in Dried Cannabis Flower and Dried Hemp Flower: Level 3 Modification Study 012201.

Author

Katchman BA, Tomchaney M, Bueschel D, Ulrich P, Freeman S, O'Brian K, Eggers R, May M, Hogan M, Thompson W, Benzinger MJ, and Bastin B

Subjects
Aspergillus, Dronabinol, Flowers, Food Microbiology, Salmonella, Cannabis, Shiga-Toxigenic Escherichia coli
Abstract

Background: The PathogenDx family of assays uses microarray technology to simultaneously detect the presence of bacterial and fungal pathogens in food products, environmental surfaces, and cannabis products., Objective: The Detectx Combined assay was validated for the detection of Aspergillus, (Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, and Aspergillus terreus), Salmonella, and a broad range of STEC (stx1 and/or 2) species. The validation consisted of two matrix studies in dried hemp flower and dried cannabis flower (>0.3% delta-9 tetrahydrocannabinol) flower, product consistency, stability, robustness, and inclusivity and exclusivity for two targets: Aspergillus and STEC., Method: The PathogenDx Detectx Combined assay was evaluated with 30 replicates in each matrix and confirmed according to the instructions outlined in this study., Results: Results of the validation study met the requirements of AOAC Standard Method Performance Requirement (SMPR®) 2020.002 and 2020.012. In the inclusivity and exclusivity study, all target isolates (Aspergillus and STEC) were correctly detected. For the exclusivity study, 26 out of 30 Aspergillus and 30 out of 30 STEC non-target strains were correctly excluded. In the matrix study, the PathogenDx Detectx Combined assay showed no significant statistical differences between confirmed results for dried hemp and cannabis flower. Robustness testing indicated that small changes to the method parameters did not impact the performance of the assay. Stability and consistency studies verified that the assay's shelf-life claims were appropriate, and manufacturing of the assay was consistent., Conclusions: The validation study indicated that the PathogenDx DetectX Combined assay was successful in detection of the new target analytes (Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, and Aspergillus terreus and STEC containing stx1 and/or 2) and could successfully recover these organisms and Salmonella from dried hemp flower and dried cannabis flower (>0.3% delta-9 tetrahydrocannabinol)., Highlights: The PathogenDx DetectX Combined Assay will be the first PTM approved multiplex assay for Aspergillus, E. coli and Salmonella that does not require an enrichment step., (© The Author(s) 2022. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2022
Full Text
View/download PDF

7. Lung Spatial Profiling Reveals a T Cell Signature in COPD Patients with Fatal SARS-CoV-2 Infection.

Author

Yang CX, Tomchaney M, Landecho MF, Zamacona BR, Marin Oto M, Zulueta J, Malo J, Knoper S, Contoli M, Papi A, Vasilescu DM, Sauler M, Straub C, Tan C, Martinez FD, Bhattacharya D, Rosas IO, Kheradmand F, Hackett TL, and Polverino F

Subjects
Humans, Lung metabolism, Proteomics, SARS-CoV-2, COVID-19, Pulmonary Disease, Chronic Obstructive metabolism
Abstract

People with pre-existing lung diseases such as chronic obstructive pulmonary disease (COPD) are more likely to get very sick from SARS-CoV-2 disease 2019 (COVID-19). Still, an interrogation of the immune response to COVID-19 infection, spatially throughout the lung structure, is lacking in patients with COPD. For this study, we characterized the immune microenvironment of the lung parenchyma, airways, and vessels of never- and ever-smokers with or without COPD, all of whom died of COVID-19, using spatial transcriptomic and proteomic profiling. The parenchyma, airways, and vessels of COPD patients, compared to control lungs had (1) significant enrichment for lung-resident CD45RO + memory CD4 + T cells; (2) downregulation of genes associated with T cell antigen priming and memory T cell differentiation; and (3) higher expression of proteins associated with SARS-CoV-2 entry and primary receptor ubiquitously across the ROIs and in particular the lung parenchyma, despite similar SARS-CoV-2 structural gene expression levels. In conclusion, the lung parenchyma, airways, and vessels of COPD patients have increased T-lymphocytes with a blunted memory CD4 T cell response and a more invasive SARS-CoV-2 infection pattern and may underlie the higher death toll observed with COVID-19.

Published
2022
Full Text
View/download PDF

8. Metformin: Experimental and Clinical Evidence for a Potential Role in Emphysema Treatment.

Author

Polverino F, Wu TD, Rojas-Quintero J, Wang X, Mayo J, Tomchaney M, Tram J, Packard S, Zhang D, Cleveland KH, Cordoba-Lanus E, Owen CA, Fawzy A, Kinney GL, Hersh CP, Hansel NN, Doubleday K, Sauler M, Tesfaigzi Y, Ledford JG, Casanova C, Zmijewski J, Konhilas J, Langlais PR, Schnellmann R, Rahman I, McCormack M, and Celli B

Subjects
Aged, Aged, 80 and over, Animals, Biomarkers metabolism, Cigarette Smoking adverse effects, Disease Progression, Female, Follow-Up Studies, Humans, Male, Mice, Mice, Inbred C57BL, Middle Aged, Pulmonary Disease, Chronic Obstructive etiology, Pulmonary Disease, Chronic Obstructive metabolism, Pulmonary Disease, Chronic Obstructive physiopathology, Pulmonary Emphysema etiology, Pulmonary Emphysema metabolism, Treatment Outcome, Metformin therapeutic use, Protective Agents therapeutic use, Pulmonary Disease, Chronic Obstructive drug therapy, Pulmonary Emphysema prevention & control
Abstract

Rationale: Cigarette smoke (CS) inhalation triggers oxidative stress and inflammation, leading to accelerated lung aging, apoptosis, and emphysema, as well as systemic pathologies. Metformin is beneficial for protecting against aging-related diseases. Objectives: We sought to investigate whether metformin may ameliorate CS-induced pathologies of emphysematous chronic obstructive pulmonary disease (COPD). Methods: Mice were exposed chronically to CS and fed metformin-enriched chow for the second half of exposure. Lung, kidney, and muscle pathologies, lung proteostasis, endoplasmic reticulum (ER) stress, mitochondrial function, and mediators of metformin effects in vivo and/or in vitro were studied. We evaluated the association of metformin use with indices of emphysema progression over 5 years of follow-up among the COPDGene (Genetic Epidemiology of COPD) study participants. The association of metformin use with the percentage of emphysema and adjusted lung density was estimated by using a linear mixed model. Measurements and Main Results: Metformin protected against CS-induced pulmonary inflammation and airspace enlargement; small airway remodeling, glomerular shrinkage, oxidative stress, apoptosis, telomere damage, aging, dysmetabolism in vivo and in vitro ; and ER stress. The AMPK (AMP-activated protein kinase) pathway was central to metformin's protective action. Within COPDGene, participants receiving metformin compared with those not receiving it had a slower progression of emphysema (-0.92%; 95% confidence interval [CI], -1.7% to -0.14%; P  = 0.02) and a slower adjusted lung density decrease (2.2 g/L; 95% CI, 0.43 to 4.0 g/L; P  = 0.01). Conclusions: Metformin protected against CS-induced lung, renal, and muscle injury; mitochondrial dysfunction; and unfolded protein responses and ER stress in mice. In humans, metformin use was associated with lesser emphysema progression over time. Our results provide a rationale for clinical trials testing the efficacy of metformin in limiting emphysema progression and its systemic consequences.

Published
2021
Full Text
View/download PDF

9. Paradoxical effects of cigarette smoke and COPD on SARS-CoV2 infection and disease.

Author

Tomchaney M, Contoli M, Mayo J, Baraldo S, Shuaizhi L, Cabel CR, Bull DA, Lick S, Malo J, Knoper S, Kim SS, Tram J, Rojas-Quintero J, Kraft M, Ledford J, Tesfaigzi Y, Martinez FD, Thorne CA, Kheradmand F, Campos SK, Papi A, and Polverino F

Abstract

Introduction: How cigarette smoke (CS) and chronic obstructive pulmonary disease (COPD) affect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severity is controversial. We investigated the protein and mRNA expression of SARS-CoV-2 entry receptor ACE2 and proteinase TMPRSS2 in lungs from COPD patients and controls, and lung tissue from mice exposed acutely and chronically to CS. Also, we investigated the effects of CS exposure on SARS-CoV-2 infection in human bronchial epithelial cells., Methods: In Cohort 1, ACE2-positive cells were quantified by immunostaining in FFPE sections from both central and peripheral airways. In Cohort 2, we quantified pulmonary ACE2 protein levels by immunostaining and ELISA, and both ACE2 and TMPRSS2 mRNA levels by RT-qPCR. In C57BL/6 WT mice exposed to air or CS for up to 6 months, pulmonary ACE2 protein levels were quantified by triple immunofluorescence staining and ELISA. The effects of CS exposure on SARS-CoV-2 infection were evaluated after 72hr in vitro infection of Calu-3 cells. After SARS-CoV-2 infection, the cells were fixed for IF staining with dsRNA-specific J2 monoclonal Ab, and cell lysates were harvested for WB of viral nucleocapsid (N) protein. Supernatants (SN) and cytoplasmic lysates were obtained to measure ACE2 levels by ELISA., Results: In both human cohorts, ACE2 protein and mRNA levels were decreased in peripheral airways from COPD patients versus both smoker and NS controls, but similar in central airways. TMPRSS2 levels were similar across groups. Mice exposed to CS had decreased ACE2 protein levels in their bronchial and alveolar epithelia versus air-exposed mice exposed to 3 and 6 months of CS. In Calu3 cells in vitro, CS-treatment abrogated infection to levels below the limit of detection. Similar results were seen with WB for viral N protein, showing peak viral protein synthesis at 72hr., Conclusions: ACE2 levels were decreased in both bronchial and alveolar epithelial cells from uninfected COPD patients versus controls, and from CS-exposed versus air-exposed mice. CS-pre-treatment did not affect ACE2 levels but potently inhibited SARS-CoV-2 replication in this in vitro model. These findings urge to further investigate the controversial effects of CS and COPD on SARS-CoV2 infection.

Published
2020
Full Text
View/download PDF

10. siRNA-Mediated Silencing of doublesex during Female Development of the Dengue Vector Mosquito Aedes aegypti.

Author

Mysore K, Sun L, Tomchaney M, Sullivan G, Adams H, Piscoya AS, Severson DW, Syed Z, and Duman-Scheel M

Subjects
Aedes anatomy & histology, Aedes growth & development, Animals, Feeding Behavior, Female, Gene Silencing, Insect Proteins genetics, Insect Vectors growth & development, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Sexual Behavior, Animal, Aedes physiology, Gene Expression Regulation, Developmental, Insect Vectors physiology, Sex Characteristics, Sex Differentiation
Abstract

The development of sex-specific traits, including the female-specific ability to bite humans and vector disease, is critical for vector mosquito reproduction and pathogen transmission. Doublesex (Dsx), a terminal transcription factor in the sex determination pathway, is known to regulate sex-specific gene expression during development of the dengue fever vector mosquito Aedes aegypti. Here, the effects of developmental siRNA-mediated dsx silencing were assessed in adult females. Targeting of dsx during A. aegypti development resulted in decreased female wing size, a correlate for body size, which is typically larger in females. siRNA-mediated targeting of dsx also resulted in decreased length of the adult female proboscis. Although dsx silencing did not impact female membrane blood feeding or mating behavior in the laboratory, decreased fecundity and fertility correlated with decreased ovary length, ovariole length, and ovariole number in dsx knockdown females. Dsx silencing also resulted in disruption of olfactory system development, as evidenced by reduced length of the female antenna and maxillary palp and the sensilla present on these structures, as well as disrupted odorant receptor expression. Female lifespan, a critical component of the ability of A. aegypti to transmit pathogens, was also significantly reduced in adult females following developmental targeting of dsx. The results of this investigation demonstrate that silencing of dsx during A. aegypti development disrupts multiple sex-specific morphological, physiological, and behavioral traits of adult females, a number of which are directly or indirectly linked to mosquito reproduction and pathogen transmission. Moreover, the olfactory phenotypes observed connect Dsx to development of the olfactory system, suggesting that A. aegypti will be an excellent system in which to further assess the developmental genetics of sex-specific chemosensation.

Published
2015
Full Text
View/download PDF

11. Role of semaphorin-1a in the developing visual system of the disease vector mosquito Aedes aegypti.

Author

Mysore K, Flannery E, Leming MT, Tomchaney M, Shi L, Sun L, O'Tousa JE, Severson DW, and Duman-Scheel M

Subjects
Animals, Chitosan chemistry, Electroretinography, Immunohistochemistry, Optic Lobe, Nonmammalian metabolism, RNA, Small Interfering chemistry, Aedes embryology, Morphogenesis physiology, Nanoparticles chemistry, Optic Lobe, Nonmammalian physiology, Semaphorins metabolism
Abstract

Background: Despite the devastating impact of mosquito-borne illnesses on human health, very little is known about mosquito developmental biology, including development of the mosquito visual system. Mosquitoes possess functional adult compound eyes as larvae, a trait that makes them an interesting model in which to study comparative developmental genetics. Here, we functionally characterize visual system development in the dengue and yellow fever vector mosquito Aedes aegypti, in which we use chitosan/siRNA nanoparticles to target the axon guidance gene semaphorin-1a (sema1a)., Results: Immunohistochemical analyses revealed the progression of visual sensory neuron targeting that results in generation of the retinotopic map in the mosquito optic lobe. Loss of sema1a function led to optic lobe phenotypes, including defective targeting of visual sensory neurons and failed formation of the retinotopic map. These sema1a knockdown phenotypes correlated with behavioral defects in larval photoavoidance., Conclusions: The results of this investigation indicate that Sema1a is required for optic lobe development in A. aegypti and highlight the behavioral importance of a functioning visual system in preadult mosquitoes., (Copyright © 2014 Wiley Periodicals, Inc.)

Published
2014
Full Text
View/download PDF

12. Examination of the genetic basis for sexual dimorphism in the Aedes aegypti (dengue vector mosquito) pupal brain.

Author

Tomchaney M, Mysore K, Sun L, Li P, Emrich SJ, Severson DW, and Duman-Scheel M

Abstract

Background: Most animal species exhibit sexually dimorphic behaviors, many of which are linked to reproduction. A number of these behaviors, including blood feeding in female mosquitoes, contribute to the global spread of vector-borne illnesses. However, knowledge concerning the genetic basis of sexually dimorphic traits is limited in any organism, including mosquitoes, especially with respect to differences in the developing nervous system., Methods: Custom microarrays were used to examine global differences in female vs. male gene expression in the developing pupal head of the dengue vector mosquito, Aedes aegypti. The spatial expression patterns of a subset of differentially expressed transcripts were examined in the developing female vs. male pupal brain through in situ hybridization experiments. Small interfering RNA (siRNA)-mediated knockdown studies were used to assess the putative role of Doublesex, a terminal component of the sex determination pathway, in the regulation of sex-specific gene expression observed in the developing pupal brain., Results: Transcripts (2,527), many of which were linked to proteolysis, the proteasome, metabolism, catabolic, and biosynthetic processes, ion transport, cell growth, and proliferation, were found to be differentially expressed in A. aegypti female vs. male pupal heads. Analysis of the spatial expression patterns for a subset of dimorphically expressed genes in the pupal brain validated the data set and also facilitated the identification of brain regions with dimorphic gene expression. In many cases, dimorphic gene expression localized to the optic lobe. Sex-specific differences in gene expression were also detected in the antennal lobe and mushroom body. siRNA-mediated gene targeting experiments demonstrated that Doublesex, a transcription factor with consensus binding sites located adjacent to many dimorphically expressed transcripts that function in neural development, is required for regulation of sex-specific gene expression in the developing A. aegypti brain., Conclusions: These studies revealed sex-specific gene expression profiles in the developing A. aegypti pupal head and identified Doublesex as a key regulator of sexually dimorphic gene expression during mosquito neural development.

Published
2014
Full Text
View/download PDF

13. Disruption of Aedes aegypti olfactory system development through chitosan/siRNA nanoparticle targeting of semaphorin-1a.

Author

Mysore K, Flannery EM, Tomchaney M, Severson DW, and Duman-Scheel M

Subjects
Aedes genetics, Animals, Entomology methods, Female, Gene Knockdown Techniques methods, Gene Targeting methods, Immunohistochemistry, Larva genetics, Larva physiology, Nanoparticles, Olfactory Pathways embryology, Olfactory Pathways physiology, Pupa genetics, Pupa physiology, Semaphorins genetics, Smell, Aedes embryology, Aedes physiology, Chitosan metabolism, RNA, Small Interfering metabolism, Semaphorins metabolism
Abstract

Despite the devastating impact of mosquito-borne illnesses on human health, surprisingly little is known about mosquito developmental biology, including development of the olfactory system, a tissue of vector importance. Analysis of mosquito olfactory developmental genetics has been hindered by a lack of means to target specific genes during the development of this sensory system. In this investigation, chitosan/siRNA nanoparticles were used to target semaphorin-1a (sema1a) during olfactory system development in the dengue and yellow fever vector mosquito Aedes aegypti. Immunohistochemical analyses and anterograde tracing of antennal sensory neurons, which were used to track the progression of olfactory development in this species, revealed antennal lobe defects in sema1a knockdown fourth instar larvae. These findings, which correlated with a larval odorant tracking behavioral phenotype, identified previously unreported roles for Sema1a in the developing insect larval olfactory system. Analysis of sema1a knockdown pupae also revealed a number of olfactory phenotypes, including olfactory receptor neuron targeting and projection neuron defects coincident with a collapse in the structure and shape of the antennal lobe and individual glomeruli. This study, which is to our knowledge the first functional genetic analysis of insect olfactory development outside of D. melanogaster, identified critical roles for Sema1a during Ae. aegypti larval and pupal olfactory development and advocates the use of chitosan/siRNA nanoparticles as an effective means of targeting genes during post-embryonic Ae. aegypti development. Use of siRNA nanoparticle methodology to understand sensory developmental genetics in mosquitoes will provide insight into the evolutionary conservation and divergence of key developmental genes which could be exploited in the development of both common and species-specific means for intervention.

Published
2013
Full Text
View/download PDF

14. siRNA-mediated gene targeting in Aedes aegypti embryos reveals that frazzled regulates vector mosquito CNS development.

Author

Clemons A, Haugen M, Le C, Mori A, Tomchaney M, Severson DW, and Duman-Scheel M

Subjects
Aedes genetics, Aedes growth & development, Animals, Drosophila Proteins, Gene Expression Regulation, Developmental, Insect Vectors, Netrin Receptors, Neurogenesis, Receptors, Cell Surface analysis, Aedes embryology, Central Nervous System growth & development, Gene Targeting methods, RNA, Small Interfering genetics, Receptors, Cell Surface physiology
Abstract

Although mosquito genome projects uncovered orthologues of many known developmental regulatory genes, extremely little is known about the development of vector mosquitoes. Here, we investigate the role of the Netrin receptor frazzled (fra) during embryonic nerve cord development of two vector mosquito species. Fra expression is detected in neurons just prior to and during axonogenesis in the embryonic ventral nerve cord of Aedes aegypti (dengue vector) and Anopheles gambiae (malaria vector). Analysis of fra function was investigated through siRNA-mediated knockdown in Ae. aegypti embryos. Confirmation of fra knockdown, which was maintained throughout embryogenesis, indicated that microinjection of siRNA is an effective method for studying gene function in Ae. aegypti embryos. Loss of fra during Ae. aegypti development results in thin and missing commissural axons. These defects are qualitatively similar to those observed in Dr. melanogaster fra null mutants. However, the Aa. aegypti knockdown phenotype is stronger and bears resemblance to the Drosophila commissureless mutant phenotype. The results of this investigation, the first targeted knockdown of a gene during vector mosquito embryogenesis, suggest that although Fra plays a critical role during development of the Ae. aegypti ventral nerve cord, mechanisms regulating embryonic commissural axon guidance have evolved in distantly related insects.

Published
2011
Full Text
View/download PDF

15. Semaphorin-1a is required for Aedes aegypti embryonic nerve cord development.

Author

Haugen M, Flannery E, Tomchaney M, Mori A, Behura SK, Severson DW, and Duman-Scheel M

Subjects
Animals, Gene Expression Regulation, Developmental genetics, Gene Expression Regulation, Developmental physiology, Nerve Tissue embryology, Semaphorins genetics, Aedes embryology, Aedes metabolism, Nerve Tissue metabolism, Semaphorins metabolism
Abstract

Although mosquito genome projects have uncovered orthologues of many known developmental regulatory genes, extremely little is known about mosquito development. In this study, the role of semaphorin-1a (sema1a) was investigated during vector mosquito embryonic ventral nerve cord development. Expression of sema1a and the plexin A (plexA) receptor are detected in the embryonic ventral nerve cords of Aedes aegypti (dengue vector) and Anopheles gambiae (malaria vector), suggesting that Sema1a signaling may regulate mosquito nervous system development. Analysis of sema1a function was investigated through siRNA-mediated knockdown in A. aegypti embryos. Knockdown of sema1a during A. aegypti development results in a number of nerve cord phenotypes, including thinning, breakage, and occasional fusion of the longitudinal connectives, thin or absent commissures, and general distortion of the nerve cord. Although analysis of Drosophila melanogaster sema1a loss-of-function mutants uncovered many similar phenotypes, aspects of the longitudinal phenotypes differed between D. melanogaster and A. aegypti. The results of this investigation suggest that Sema1a is required for development of the insect ventral nerve cord, but that the developmental roles of this guidance molecule have diverged in dipteran insects.

Published
2011
Full Text
View/download PDF

16. Aedes aegypti: an emerging model for vector mosquito development.

Author

Clemons A, Haugen M, Flannery E, Tomchaney M, Kast K, Jacowski C, Le C, Mori A, Simanton Holland W, Sarro J, Severson DW, and Duman-Scheel M

Subjects
Animals, Gene Expression Regulation, Developmental, Life Cycle Stages, Aedes genetics, Aedes growth & development, Genetic Techniques, Insect Vectors genetics, Insect Vectors growth & development, Models, Biological
Abstract

Blood-feeding mosquitoes, including the dengue and yellow fever vector Aedes aegypti, transmit many of the world's deadliest diseases. Such diseases have resurged in developing countries and pose clear threats for epidemic outbreaks in developed countries. Recent mosquito genome projects have stimulated interest in the potential for arthropod-borne disease control by genetic manipulation of vector insects. Targets of particular interest include genes that regulate development. However, although the Ae. aegypti genome project uncovered homologs of many known developmental regulatory genes, little is known of the genetic regulation of development in Ae. aegypti or other vector mosquitoes. This article provides an overview of the background, husbandry, and potential uses of Ae. aegypti as a model species. Methods for culturing, collecting and fixing developing tissues, analyzing gene and protein expression, and knocking down genes are permitting detailed analyses of the functions of developmental regulatory genes and the selective inhibition of such genes during Ae. aegypti development. This methodology, much of which is applicable to other mosquito species, is useful to both the comparative development and vector research communities.

Published
2010
Full Text
View/download PDF

17. Whole-mount in situ hybridization for analysis of gene expression during Aedes aegypti development.

Author

Haugen M, Tomchaney M, Kast K, Flannery E, Clemons A, Jacowski C, Simanton Holland W, Le C, Severson D, and Duman-Scheel M

Subjects
Animals, Culture Techniques methods, Aedes genetics, Aedes growth & development, Gene Expression Regulation, Developmental, In Situ Hybridization methods, Insect Vectors genetics, Insect Vectors growth & development
Abstract

Blood-feeding mosquitoes, including the dengue and yellow fever vector Aedes aegypti, transmit many of the world's deadliest diseases. Such diseases have resurged in developing countries and pose clear threats for epidemic outbreaks in developed countries. Recent mosquito genome projects have stimulated interest in the potential for arthropod-borne disease control by genetic manipulation of vector insects, and genes that regulate development are of particular interest. This protocol for whole-mount in situ hybridization can be used to analyze gene expression in Ae. aegypti embryos and larvae, a critical aspect of understanding developmental gene function in this vector mosquito.

Published
2010
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results