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2. In-hospital and 6-month outcomes in patients with COVID-19 supported with extracorporeal membrane oxygenation (EuroECMO-COVID): a multicentre, prospective observational study

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Lorusso, R, De Piero, M, Mariani, S, Di Mauro, M, Folliguet, T, Taccone, F, Camporota, L, Swol, J, Wiedemann, D, Belliato, M, Broman, L, Vuylsteke, A, Kassif, Y, Scandroglio, A, Fanelli, V, Gaudard, P, Ledot, S, Barker, J, Boeken, U, Maier, S, Kersten, A, Meyns, B, Pozzi, M, Pedersen, F, Schellongowski, P, Kirali, K, Barrett, N, Riera, J, Mueller, T, Belohlavek, J, Lo Coco, V, Van der Horst, I, Van Bussel, B, Schnabel, R, Delnoij, T, Bolotin, G, Lorini, L, Schmiady, M, Schibilsky, D, Kowalewski, M, Pinto, L, Silva, P, Kornilov, I, Blandino Ortiz, A, Vercaemst, L, Finney, S, Roeleveld, P, Di Nardo, M, Hennig, F, Antonini, M, Davidson, M, Jones, T, Staudinger, T, Mair, P, Kilo, J, Krapf, C, Erbert, K, Peer, A, Bonaros, N, Kotheletner, F, Krenner Mag, N, Shestakova, L, Hermans, G, Dauwe, D, Meersseman, P, Stockman, B, Nobile, L, Lhereux, O, Nrasseurs, A, Creuter, J, De Backer, D, Giglioli, S, Michiels, G, Foulon, P, Raes, M, Rodrigus, I, Allegaert, M, Jorens, P, Debeucklare, G, Piagnerelli, M, Biston, P, Peperstraete, H, Vandewiele, K, Germay, O, Vandeweghe, D, Havrin, S, Bourgeois, M, Lagny, M, Alois, G, Lavios, N, Misset, B, Courcelle, R, Timmermans, P, Yilmaz, A, Vantomout, M, Lehaen, J, Jassen, A, Guterman, H, Strauven, M, Lormans, P, Verhamme, B, Vandewaeter, C, Bonte, F, Vionne, D, Balik, M, Blaha, J, Lips, M, Othal, M, Bursa, F, Spacek, R, Christensen, S, Jorgensen, V, Sorensen, M, Madsen, S, Puss, S, Beljantsev, A, Saiydoun, G, Fiore, A, Colson, P, Bazalgette, F, Capdevila, X, Kollen, S, Muller, L, Obadia, J, Dubien, P, Ajrhourh, L, Guinot, P, Zarka, J, Besserve, P, Malfertheiner, M, Dreier, E, Heinze, B, Akhyari, P, Lichtenberg, A, Aubin, H, Assman, A, Saeed, D, Thiele, H, Baumgaertel, M, Schmitto, J, Ruslan, N, Haverich, A, Thielmann, M, Brenner, T, Ruhpawar, A, Benk, C, Czerny, M, Staudacher, D, Beyersdorf, F, Kalbhenn, J, Henn, P, Popov, A, Iuliu, T, Muellenbach, R, Reyher, C, Rolfes, C, Lotz, G, Sonntagbauer, M, Winkels, H, Fichte, J, Stohr, R, Kalverkamp, S, Karagiannidis, C, Schafer, S, Svetlitchny, A, Hopf, H, Jarczak, D, Groesdonk, H, Rommer, M, Hirsch, J, Kaehny, C, Soufleris, D, Gavriilidis, G, Pontikis, K, Kyriakopoulou, M, Kyriakoudi, A, O'Brien, S, Conrick-Martin, I, Carton, E, Makhoul, M, Ben-Ari, J, Hadash, A, Kogan, A, Kassif Lerner, R, Abu-Shakra, A, Matan, M, Balawona, A, Kachel, E, Altshuler, R, Galante, O, Fuchs, L, Almog, Y, Ishay, Y, Lichter, Y, Gal-oz, A, Carmi, U, Nini, A, Soroksky, A, Dekel, H, Rozman, Z, Tayem, E, Ilgiyaev, E, Hochman, Y, Miltau, D, Rapoport, A, Eden, A, Kompanietz, D, Yousif, M, Golos, M, Grazioli, L, Ghitti, D, Loforte, A, Di Luca, D, Baiocchi, M, Pacini, D, Cappai, A, Meani, P, Mondino, M, Russo, C, Ranucci, M, Fina, D, Cotza, M, Ballotta, A, Landoni, G, Nardelli, P, Fominski, E, Brazzi, L, Montrucchio, G, Sales, G, Simonetti, U, Livigni, S, Silengo, D, Arena, G, Sovatzis, S, Degani, A, Riccardi, M, Milanesi, E, Raffa, G, Martucci, G, Arcadipane, A, Panarello, G, Chiarini, G, Cattaneo, S, Puglia, C, Benussi, S, Foti, G, Giani, M, Bombino, M, Costa, M, Rona, R, Avalli, L, Donati, A, Carozza, R, Gasparri, F, Carsetti, A, Piciche, M, Marinello, A, Danzi, V, Zanin, A, Condello, I, Fiore, F, Moscarelli, M, Nasso, G, Speziale, G, Sandrelli, L, Montalto, A, Musumeci, F, Circelli, A, Russo, E, Agnoletti, V, Rociola, R, Milano, A, Pilato, E, Comentale, G, Montisci, A, Alessandri, F, Tosi, A, Pugliese, F, Giordano, G, Carelli, S, Grieco, D, Dell'Anna, A, Antonelli, M, Ramoni, E, Zulueta, J, Del Giglio, M, Petracca, S, Bertini, P, Guarracino, F, De Simone, L, Angeletti, P, Forfori, F, Taraschi, F, Quintiliani, V, Samalavicius, R, Jankuviene, A, Scupakova, N, Urbonas, K, Kapturauskas, J, Soerensen, G, Suwalski, P, Linhares Santos, L, Marques, A, Miranda, M, Teixeira, S, Salgueiro, A, Pereira, F, Ketskalo, M, Tsarenko, S, Shilova, A, Afukov, I, Popugaev, K, Minin, S, Shelukhin, D, Malceva, O, Gleb, M, Skopets, A, Kornelyuk, R, Kulikov, A, Okhrimchuk, V, Turchaninov, A, Petrushin, M, Sheck, A, Mekulov, A, Ciryateva, S, Urusov, D, Gorjup, V, Golicnik, A, Goslar, T, Ferrer, R, Martinez-Martinez, M, Argudo, E, Palmer, N, De Pablo Sanchez, R, Juan Higuera, L, Arnau Blasco, L, Marquez, J, Sbraga, F, Fuset, M, De Gopegui, P, Claraco, L, De Ayala, J, Peiro, M, Ricart, P, Martinez, S, Chavez, F, Fabra, M, Sandoval, E, Toapanta, D, Carraminana, A, Tellez, A, Ososio, J, Milan, P, Rodriguez, J, Andoni, G, Gutierrez, C, Perez de la Sota, E, Eixeres-Esteve, A, Garcia-Maellas, M, Gutierrez-Gutierrez, J, Arboleda-Salazar, R, Santa Teresa, P, Jaspe, A, Garrido, A, Castaneda, G, Alcantara, S, Martinez, N, Perez, M, Villanueva, H, Vidal Gonzalez, A, Paez, J, Santon, A, Perez, C, Lopez, M, Rubio Lopez, M, Gordillo, A, Naranjo-Izurieta, J, Munoz, J, Alcalde, I, Onieva, F, Gimeno Costa, R, Perez, F, Madrid, I, Gordon, M, Albacete Moreno, C, Perez, D, Lopez, N, Martinenz, D, Blanco-Schweizer, P, Diez, C, Prieto, A, Renedo, G, Bustamante, E, Cicuendez, R, Citores, R, Boado, V, Garcia, K, Voces, R, Domezain, M, Nunez Martinez, J, Vicente, R, Martin, D, Andreu, A, Gomez Casal, V, Chico, I, Menor, E, Vara, S, Gamacho, J, Perez-Chomon, H, Javier Gonzales, F, Barrero, I, Martin-Villen, L, Fernandez, E, Mendoza, M, Navarro, J, Colomina Climent, J, Gonzales-Perez, A, Muniz-Albaceita, G, Amado, L, Rodriguez, R, Ruiz, E, Eiras, M, Grins, E, Magnus, R, Kanetoft, M, Eidevald, M, Watson, P, Vogt, P, Steiger, P, Aigner, T, Weber, A, Grunefelder, J, Kunz, M, Grapow, M, Aymard, T, Reser, D, Agus, G, Consiglio, J, Haenggi, M, Hansjoerg, J, Iten, M, Doeble, T, Zenklusen, U, Bechtold, X, Faedda, G, Iafrate, M, Rohjer, A, Bergamaschi, L, Maessen, J, Reis Miranda, D, Endeman, H, Gommers, D, Meuwese, C, Maas, J, Van Gijlswijk, M, Van Berg, R, Candura, D, Van der Linden, M, Kant, M, Van der Heijden, J, Scholten, E, Van Belle-van Haren, N, Lagrand, W, Vlaar, A, De Jong, S, Cander, B, Sargin, M, Ugur, M, Kaygin, M, Daly, K, Agnew, N, Head, L, Kelly, L, Anoma, G, Russell, C, Aquino, V, Scott, I, Flemming, L, Gillon, S, Moore, O, Gelandt, E, Auzinger, G, Patel, S, Loveridge, R, Lorusso R., De Piero M. E., Mariani S., Di Mauro M., Folliguet T., Taccone F. S., Camporota L., Swol J., Wiedemann D., Belliato M., Broman L. M., Vuylsteke A., Kassif Y., Scandroglio A. M., Fanelli V., Gaudard P., Ledot S., Barker J., Boeken U., Maier S., Kersten A., Meyns B., Pozzi M., Pedersen F. M., Schellongowski P., Kirali K., Barrett N., Riera J., Mueller T., Belohlavek J., Lo Coco V., Van der Horst I. C. C., Van Bussel B. C. T., Schnabel R. M., Delnoij T., Bolotin G., Lorini L., Schmiady M. O., Schibilsky D., Kowalewski M., Pinto L. F., Silva P. E., Kornilov I., Blandino Ortiz A., Vercaemst L., Finney S., Roeleveld P. P., Di Nardo M., Hennig F., Antonini M. V., Davidson M., Jones T. J., Staudinger T., Mair P., Kilo J., Krapf C., Erbert K., Peer A., Bonaros N., Kotheletner F., Krenner Mag N., Shestakova L., Hermans G., Dauwe D., Meersseman P., Stockman B., Nobile L., Lhereux O., Nrasseurs A., Creuter J., De Backer D., Giglioli S., Michiels G., Foulon P., Raes M., Rodrigus I., Allegaert M., Jorens P., Debeucklare G., Piagnerelli M., Biston P., Peperstraete H., Vandewiele K., Germay O., Vandeweghe D., Havrin S., Bourgeois M., Lagny M. -G., Alois G., Lavios N., Misset B., Courcelle R., Timmermans P. J., Yilmaz A., Vantomout M., Lehaen J., Jassen A., Guterman H., Strauven M., Lormans P., Verhamme B., Vandewaeter C., Bonte F., Vionne D., Balik M., Blaha J., Lips M., Othal M., Bursa F., Spacek R., Christensen S., Jorgensen V., Sorensen M., Madsen S. A., Puss S., Beljantsev A., Saiydoun G., Fiore A., Colson P., Bazalgette F., Capdevila X., Kollen S., Muller L., Obadia J. -F., Dubien P. -Y., Ajrhourh L., Guinot P. G., Zarka J., Besserve P., Malfertheiner M. V., Dreier E., Heinze B., Akhyari P., Lichtenberg A., Aubin H., Assman A., Saeed D., Thiele H., Baumgaertel M., Schmitto J. D., Ruslan N., Haverich A., Thielmann M., Brenner T., Ruhpawar A., Benk C., Czerny M., Staudacher D. L., Beyersdorf F., Kalbhenn J., Henn P., Popov A. -F., Iuliu T., Muellenbach R., Reyher C., Rolfes C., Lotz G., Sonntagbauer M., Winkels H., Fichte J., Stohr R., Kalverkamp S., Karagiannidis C., Schafer S., Svetlitchny A., Hopf H. -B., Jarczak D., Groesdonk H., Rommer M., Hirsch J., Kaehny C., Soufleris D., Gavriilidis G., Pontikis K., Kyriakopoulou M., Kyriakoudi A., O'Brien S., Conrick-Martin I., Carton E., Makhoul M., Ben-Ari J., Hadash A., Kogan A., Kassif Lerner R., Abu-Shakra A., Matan M., Balawona A., Kachel E., Altshuler R., Galante O., Fuchs L., Almog Y., Ishay Y. S., Lichter Y., Gal-oz A., Carmi U., Nini A., Soroksky A., Dekel H., Rozman Z., Tayem E., Ilgiyaev E., Hochman Y., Miltau D., Rapoport A., Eden A., Kompanietz D., Yousif M., Golos M., Grazioli L., Ghitti D., Loforte A., Di Luca D., Baiocchi M., Pacini D., Cappai A., Meani P., Mondino M., Russo C. F., Ranucci M., Fina D., Cotza M., Ballotta A., Landoni G., Nardelli P., Fominski E. V., Brazzi L., Montrucchio G., Sales G., Simonetti U., Livigni S., Silengo D., Arena G., Sovatzis S. S., Degani A., Riccardi M., Milanesi E., Raffa G., Martucci G., Arcadipane A., Panarello G., Chiarini G., Cattaneo S., Puglia C., Benussi S., Foti G., Giani M., Bombino M., Costa M. C., Rona R., Avalli L., Donati A., Carozza R., Gasparri F., Carsetti A., Piciche M., Marinello A., Danzi V., Zanin A., Condello I., Fiore F., Moscarelli M., Nasso G., Speziale G., Sandrelli L., Montalto A., Musumeci F., Circelli A., Russo E., Agnoletti V., Rociola R., Milano A. D., Pilato E., Comentale G., Montisci A., Alessandri F., Tosi A., Pugliese F., Giordano G., Carelli S., Grieco D. L., Dell'Anna A. M., Antonelli M., Ramoni E., Zulueta J., Del Giglio M., Petracca S., Bertini P., Guarracino F., De Simone L., Angeletti P. M., Forfori F., Taraschi F., Quintiliani V. N., Samalavicius R., Jankuviene A., Scupakova N., Urbonas K., Kapturauskas J., Soerensen G., Suwalski P., Linhares Santos L., Marques A., Miranda M., Teixeira S., Salgueiro A., Pereira F., Ketskalo M., Tsarenko S., Shilova A., Afukov I., Popugaev K., Minin S., Shelukhin D., Malceva O., Gleb M., Skopets A., Kornelyuk R., Kulikov A., Okhrimchuk V., Turchaninov A., Petrushin M., Sheck A., Mekulov A., Ciryateva S., Urusov D., Gorjup V., Golicnik A., Goslar T., Ferrer R., Martinez-Martinez M., Argudo E., Palmer N., De Pablo Sanchez R., Juan Higuera L., Arnau Blasco L., Marquez J. A., Sbraga F., Fuset M. P., De Gopegui P. R., Claraco L. M., De Ayala J. A., Peiro M., Ricart P., Martinez S., Chavez F., Fabra M., Sandoval E., Toapanta D., Carraminana A., Tellez A., Ososio J., Milan P., Rodriguez J., Andoni G., Gutierrez C., Perez de la Sota E., Eixeres-Esteve A., Garcia-Maellas M. T., Gutierrez-Gutierrez J., Arboleda-Salazar R., Santa Teresa P., Jaspe A., Garrido A., Castaneda G., Alcantara S., Martinez N., Perez M., Villanueva H., Vidal Gonzalez A., Paez J., Santon A., Perez C., Lopez M., Rubio Lopez M. I., Gordillo A., Naranjo-Izurieta J., Munoz J., Alcalde I., Onieva F., Gimeno Costa R., Perez F., Madrid I., Gordon M., Albacete Moreno C. L., Perez D., Lopez N., Martinenz D., Blanco-Schweizer P., Diez C., Prieto A., Renedo G., Bustamante E., Cicuendez R., Citores R., Boado V., Garcia K., Voces R., Domezain M., Nunez Martinez J. M., Vicente R., Martin D., Andreu A., Gomez Casal V., Chico I., Menor E. M., Vara S., Gamacho J., Perez-Chomon H., Javier Gonzales F., Barrero I., Martin-Villen L., Fernandez E., Mendoza M., Navarro J., Colomina Climent J., Gonzales-Perez A., Muniz-Albaceita G., Amado L., Rodriguez R., Ruiz E., Eiras M., Grins E., Magnus R., Kanetoft M., Eidevald M., Watson P., Vogt P. R., Steiger P., Aigner T., Weber A., Grunefelder J., Kunz M., Grapow M., Aymard T., Reser D., Agus G., Consiglio J., Haenggi M., Hansjoerg J., Iten M., Doeble T., Zenklusen U., Bechtold X., Faedda G., Iafrate M., Rohjer A., Bergamaschi L., Maessen J., Reis Miranda D., Endeman H., Gommers D., Meuwese C., Maas J., Van Gijlswijk M. J., Van Berg R. N., Candura D., Van der Linden M., Kant M., Van der Heijden J. J., Scholten E., Van Belle-van Haren N., Lagrand W. K., Vlaar A. P., De Jong S., Cander B., Sargin M., Ugur M., Kaygin M. A., Daly K., Agnew N., Head L., Kelly L., Anoma G., Russell C., Aquino V., Scott I., Flemming L., Gillon S., Moore O., Gelandt E., Auzinger G., Patel S., Loveridge R., Lorusso, R, De Piero, M, Mariani, S, Di Mauro, M, Folliguet, T, Taccone, F, Camporota, L, Swol, J, Wiedemann, D, Belliato, M, Broman, L, Vuylsteke, A, Kassif, Y, Scandroglio, A, Fanelli, V, Gaudard, P, Ledot, S, Barker, J, Boeken, U, Maier, S, Kersten, A, Meyns, B, Pozzi, M, Pedersen, F, Schellongowski, P, Kirali, K, Barrett, N, Riera, J, Mueller, T, Belohlavek, J, Lo Coco, V, Van der Horst, I, Van Bussel, B, Schnabel, R, Delnoij, T, Bolotin, G, Lorini, L, Schmiady, M, Schibilsky, D, Kowalewski, M, Pinto, L, Silva, P, Kornilov, I, Blandino Ortiz, A, Vercaemst, L, Finney, S, Roeleveld, P, Di Nardo, M, Hennig, F, Antonini, M, Davidson, M, Jones, T, Staudinger, T, Mair, P, Kilo, J, Krapf, C, Erbert, K, Peer, A, Bonaros, N, Kotheletner, F, Krenner Mag, N, Shestakova, L, Hermans, G, Dauwe, D, Meersseman, P, Stockman, B, Nobile, L, Lhereux, O, Nrasseurs, A, Creuter, J, De Backer, D, Giglioli, S, Michiels, G, Foulon, P, Raes, M, Rodrigus, I, Allegaert, M, Jorens, P, Debeucklare, G, Piagnerelli, M, Biston, P, Peperstraete, H, Vandewiele, K, Germay, O, Vandeweghe, D, Havrin, S, Bourgeois, M, Lagny, M, Alois, G, Lavios, N, Misset, B, Courcelle, R, Timmermans, P, Yilmaz, A, Vantomout, M, Lehaen, J, Jassen, A, Guterman, H, Strauven, M, Lormans, P, Verhamme, B, Vandewaeter, C, Bonte, F, Vionne, D, Balik, M, Blaha, J, Lips, M, Othal, M, Bursa, F, Spacek, R, Christensen, S, Jorgensen, V, Sorensen, M, Madsen, S, Puss, S, Beljantsev, A, Saiydoun, G, Fiore, A, Colson, P, Bazalgette, F, Capdevila, X, Kollen, S, Muller, L, Obadia, J, Dubien, P, Ajrhourh, L, Guinot, P, Zarka, J, Besserve, P, Malfertheiner, M, Dreier, E, Heinze, B, Akhyari, P, Lichtenberg, A, Aubin, H, Assman, A, Saeed, D, Thiele, H, Baumgaertel, M, Schmitto, J, Ruslan, N, Haverich, A, Thielmann, M, Brenner, T, Ruhpawar, A, Benk, C, Czerny, M, Staudacher, D, Beyersdorf, F, Kalbhenn, J, Henn, P, Popov, A, Iuliu, T, Muellenbach, R, Reyher, C, Rolfes, C, Lotz, G, Sonntagbauer, M, Winkels, H, Fichte, J, Stohr, R, Kalverkamp, S, Karagiannidis, C, Schafer, S, Svetlitchny, A, Hopf, H, Jarczak, D, Groesdonk, H, Rommer, M, Hirsch, J, Kaehny, C, Soufleris, D, Gavriilidis, G, Pontikis, K, Kyriakopoulou, M, Kyriakoudi, A, O'Brien, S, Conrick-Martin, I, Carton, E, Makhoul, M, Ben-Ari, J, Hadash, A, Kogan, A, Kassif Lerner, R, Abu-Shakra, A, Matan, M, Balawona, A, Kachel, E, Altshuler, R, Galante, O, Fuchs, L, Almog, Y, Ishay, Y, Lichter, Y, Gal-oz, A, Carmi, U, Nini, A, Soroksky, A, Dekel, H, Rozman, Z, Tayem, E, Ilgiyaev, E, Hochman, Y, Miltau, D, Rapoport, A, Eden, A, Kompanietz, D, Yousif, M, Golos, M, Grazioli, L, Ghitti, D, Loforte, A, Di Luca, D, Baiocchi, M, Pacini, D, Cappai, A, Meani, P, Mondino, M, Russo, C, Ranucci, M, Fina, D, Cotza, M, Ballotta, A, Landoni, G, Nardelli, P, Fominski, E, Brazzi, L, Montrucchio, G, Sales, G, Simonetti, U, Livigni, S, Silengo, D, Arena, G, Sovatzis, S, Degani, A, Riccardi, M, Milanesi, E, Raffa, G, Martucci, G, Arcadipane, A, Panarello, G, Chiarini, G, Cattaneo, S, Puglia, C, Benussi, S, Foti, G, Giani, M, Bombino, M, Costa, M, Rona, R, Avalli, L, Donati, A, Carozza, R, Gasparri, F, Carsetti, A, Piciche, M, Marinello, A, Danzi, V, Zanin, A, Condello, I, Fiore, F, Moscarelli, M, Nasso, G, Speziale, G, Sandrelli, L, Montalto, A, Musumeci, F, Circelli, A, Russo, E, Agnoletti, V, Rociola, R, Milano, A, Pilato, E, Comentale, G, Montisci, A, Alessandri, F, Tosi, A, Pugliese, F, Giordano, G, Carelli, S, Grieco, D, Dell'Anna, A, Antonelli, M, Ramoni, E, Zulueta, J, Del Giglio, M, Petracca, S, Bertini, P, Guarracino, F, De Simone, L, Angeletti, P, Forfori, F, Taraschi, F, Quintiliani, V, Samalavicius, R, Jankuviene, A, Scupakova, N, Urbonas, K, Kapturauskas, J, Soerensen, G, Suwalski, P, Linhares Santos, L, Marques, A, Miranda, M, Teixeira, S, Salgueiro, A, Pereira, F, Ketskalo, M, Tsarenko, S, Shilova, A, Afukov, I, Popugaev, K, Minin, S, Shelukhin, D, Malceva, O, Gleb, M, Skopets, A, Kornelyuk, R, Kulikov, A, Okhrimchuk, V, Turchaninov, A, Petrushin, M, Sheck, A, Mekulov, A, Ciryateva, S, Urusov, D, Gorjup, V, Golicnik, A, Goslar, T, Ferrer, R, Martinez-Martinez, M, Argudo, E, Palmer, N, De Pablo Sanchez, R, Juan Higuera, L, Arnau Blasco, L, Marquez, J, Sbraga, F, Fuset, M, De Gopegui, P, Claraco, L, De Ayala, J, Peiro, M, Ricart, P, Martinez, S, Chavez, F, Fabra, M, Sandoval, E, Toapanta, D, Carraminana, A, Tellez, A, Ososio, J, Milan, P, Rodriguez, J, Andoni, G, Gutierrez, C, Perez de la Sota, E, Eixeres-Esteve, A, Garcia-Maellas, M, Gutierrez-Gutierrez, J, Arboleda-Salazar, R, Santa Teresa, P, Jaspe, A, Garrido, A, Castaneda, G, Alcantara, S, Martinez, N, Perez, M, Villanueva, H, Vidal Gonzalez, A, Paez, J, Santon, A, Perez, C, Lopez, M, Rubio Lopez, M, Gordillo, A, Naranjo-Izurieta, J, Munoz, J, Alcalde, I, Onieva, F, Gimeno Costa, R, Perez, F, Madrid, I, Gordon, M, Albacete Moreno, C, Perez, D, Lopez, N, Martinenz, D, Blanco-Schweizer, P, Diez, C, Prieto, A, Renedo, G, Bustamante, E, Cicuendez, R, Citores, R, Boado, V, Garcia, K, Voces, R, Domezain, M, Nunez Martinez, J, Vicente, R, Martin, D, Andreu, A, Gomez Casal, V, Chico, I, Menor, E, Vara, S, Gamacho, J, Perez-Chomon, H, Javier Gonzales, F, Barrero, I, Martin-Villen, L, Fernandez, E, Mendoza, M, Navarro, J, Colomina Climent, J, Gonzales-Perez, A, Muniz-Albaceita, G, Amado, L, Rodriguez, R, Ruiz, E, Eiras, M, Grins, E, Magnus, R, Kanetoft, M, Eidevald, M, Watson, P, Vogt, P, Steiger, P, Aigner, T, Weber, A, Grunefelder, J, Kunz, M, Grapow, M, Aymard, T, Reser, D, Agus, G, Consiglio, J, Haenggi, M, Hansjoerg, J, Iten, M, Doeble, T, Zenklusen, U, Bechtold, X, Faedda, G, Iafrate, M, Rohjer, A, Bergamaschi, L, Maessen, J, Reis Miranda, D, Endeman, H, Gommers, D, Meuwese, C, Maas, J, Van Gijlswijk, M, Van Berg, R, Candura, D, Van der Linden, M, Kant, M, Van der Heijden, J, Scholten, E, Van Belle-van Haren, N, Lagrand, W, Vlaar, A, De Jong, S, Cander, B, Sargin, M, Ugur, M, Kaygin, M, Daly, K, Agnew, N, Head, L, Kelly, L, Anoma, G, Russell, C, Aquino, V, Scott, I, Flemming, L, Gillon, S, Moore, O, Gelandt, E, Auzinger, G, Patel, S, Loveridge, R, Lorusso R., De Piero M. E., Mariani S., Di Mauro M., Folliguet T., Taccone F. S., Camporota L., Swol J., Wiedemann D., Belliato M., Broman L. M., Vuylsteke A., Kassif Y., Scandroglio A. M., Fanelli V., Gaudard P., Ledot S., Barker J., Boeken U., Maier S., Kersten A., Meyns B., Pozzi M., Pedersen F. M., Schellongowski P., Kirali K., Barrett N., Riera J., Mueller T., Belohlavek J., Lo Coco V., Van der Horst I. C. C., Van Bussel B. C. T., Schnabel R. M., Delnoij T., Bolotin G., Lorini L., Schmiady M. O., Schibilsky D., Kowalewski M., Pinto L. F., Silva P. E., Kornilov I., Blandino Ortiz A., Vercaemst L., Finney S., Roeleveld P. P., Di Nardo M., Hennig F., Antonini M. V., Davidson M., Jones T. J., Staudinger T., Mair P., Kilo J., Krapf C., Erbert K., Peer A., Bonaros N., Kotheletner F., Krenner Mag N., Shestakova L., Hermans G., Dauwe D., Meersseman P., Stockman B., Nobile L., Lhereux O., Nrasseurs A., Creuter J., De Backer D., Giglioli S., Michiels G., Foulon P., Raes M., Rodrigus I., Allegaert M., Jorens P., Debeucklare G., Piagnerelli M., Biston P., Peperstraete H., Vandewiele K., Germay O., Vandeweghe D., Havrin S., Bourgeois M., Lagny M. -G., Alois G., Lavios N., Misset B., Courcelle R., Timmermans P. J., Yilmaz A., Vantomout M., Lehaen J., Jassen A., Guterman H., Strauven M., Lormans P., Verhamme B., Vandewaeter C., Bonte F., Vionne D., Balik M., Blaha J., Lips M., Othal M., Bursa F., Spacek R., Christensen S., Jorgensen V., Sorensen M., Madsen S. A., Puss S., Beljantsev A., Saiydoun G., Fiore A., Colson P., Bazalgette F., Capdevila X., Kollen S., Muller L., Obadia J. -F., Dubien P. -Y., Ajrhourh L., Guinot P. G., Zarka J., Besserve P., Malfertheiner M. V., Dreier E., Heinze B., Akhyari P., Lichtenberg A., Aubin H., Assman A., Saeed D., Thiele H., Baumgaertel M., Schmitto J. D., Ruslan N., Haverich A., Thielmann M., Brenner T., Ruhpawar A., Benk C., Czerny M., Staudacher D. L., Beyersdorf F., Kalbhenn J., Henn P., Popov A. -F., Iuliu T., Muellenbach R., Reyher C., Rolfes C., Lotz G., Sonntagbauer M., Winkels H., Fichte J., Stohr R., Kalverkamp S., Karagiannidis C., Schafer S., Svetlitchny A., Hopf H. -B., Jarczak D., Groesdonk H., Rommer M., Hirsch J., Kaehny C., Soufleris D., Gavriilidis G., Pontikis K., Kyriakopoulou M., Kyriakoudi A., O'Brien S., Conrick-Martin I., Carton E., Makhoul M., Ben-Ari J., Hadash A., Kogan A., Kassif Lerner R., Abu-Shakra A., Matan M., Balawona A., Kachel E., Altshuler R., Galante O., Fuchs L., Almog Y., Ishay Y. S., Lichter Y., Gal-oz A., Carmi U., Nini A., Soroksky A., Dekel H., Rozman Z., Tayem E., Ilgiyaev E., Hochman Y., Miltau D., Rapoport A., Eden A., Kompanietz D., Yousif M., Golos M., Grazioli L., Ghitti D., Loforte A., Di Luca D., Baiocchi M., Pacini D., Cappai A., Meani P., Mondino M., Russo C. F., Ranucci M., Fina D., Cotza M., Ballotta A., Landoni G., Nardelli P., Fominski E. V., Brazzi L., Montrucchio G., Sales G., Simonetti U., Livigni S., Silengo D., Arena G., Sovatzis S. S., Degani A., Riccardi M., Milanesi E., Raffa G., Martucci G., Arcadipane A., Panarello G., Chiarini G., Cattaneo S., Puglia C., Benussi S., Foti G., Giani M., Bombino M., Costa M. C., Rona R., Avalli L., Donati A., Carozza R., Gasparri F., Carsetti A., Piciche M., Marinello A., Danzi V., Zanin A., Condello I., Fiore F., Moscarelli M., Nasso G., Speziale G., Sandrelli L., Montalto A., Musumeci F., Circelli A., Russo E., Agnoletti V., Rociola R., Milano A. D., Pilato E., Comentale G., Montisci A., Alessandri F., Tosi A., Pugliese F., Giordano G., Carelli S., Grieco D. L., Dell'Anna A. M., Antonelli M., Ramoni E., Zulueta J., Del Giglio M., Petracca S., Bertini P., Guarracino F., De Simone L., Angeletti P. M., Forfori F., Taraschi F., Quintiliani V. N., Samalavicius R., Jankuviene A., Scupakova N., Urbonas K., Kapturauskas J., Soerensen G., Suwalski P., Linhares Santos L., Marques A., Miranda M., Teixeira S., Salgueiro A., Pereira F., Ketskalo M., Tsarenko S., Shilova A., Afukov I., Popugaev K., Minin S., Shelukhin D., Malceva O., Gleb M., Skopets A., Kornelyuk R., Kulikov A., Okhrimchuk V., Turchaninov A., Petrushin M., Sheck A., Mekulov A., Ciryateva S., Urusov D., Gorjup V., Golicnik A., Goslar T., Ferrer R., Martinez-Martinez M., Argudo E., Palmer N., De Pablo Sanchez R., Juan Higuera L., Arnau Blasco L., Marquez J. A., Sbraga F., Fuset M. P., De Gopegui P. R., Claraco L. M., De Ayala J. A., Peiro M., Ricart P., Martinez S., Chavez F., Fabra M., Sandoval E., Toapanta D., Carraminana A., Tellez A., Ososio J., Milan P., Rodriguez J., Andoni G., Gutierrez C., Perez de la Sota E., Eixeres-Esteve A., Garcia-Maellas M. T., Gutierrez-Gutierrez J., Arboleda-Salazar R., Santa Teresa P., Jaspe A., Garrido A., Castaneda G., Alcantara S., Martinez N., Perez M., Villanueva H., Vidal Gonzalez A., Paez J., Santon A., Perez C., Lopez M., Rubio Lopez M. I., Gordillo A., Naranjo-Izurieta J., Munoz J., Alcalde I., Onieva F., Gimeno Costa R., Perez F., Madrid I., Gordon M., Albacete Moreno C. L., Perez D., Lopez N., Martinenz D., Blanco-Schweizer P., Diez C., Prieto A., Renedo G., Bustamante E., Cicuendez R., Citores R., Boado V., Garcia K., Voces R., Domezain M., Nunez Martinez J. M., Vicente R., Martin D., Andreu A., Gomez Casal V., Chico I., Menor E. M., Vara S., Gamacho J., Perez-Chomon H., Javier Gonzales F., Barrero I., Martin-Villen L., Fernandez E., Mendoza M., Navarro J., Colomina Climent J., Gonzales-Perez A., Muniz-Albaceita G., Amado L., Rodriguez R., Ruiz E., Eiras M., Grins E., Magnus R., Kanetoft M., Eidevald M., Watson P., Vogt P. R., Steiger P., Aigner T., Weber A., Grunefelder J., Kunz M., Grapow M., Aymard T., Reser D., Agus G., Consiglio J., Haenggi M., Hansjoerg J., Iten M., Doeble T., Zenklusen U., Bechtold X., Faedda G., Iafrate M., Rohjer A., Bergamaschi L., Maessen J., Reis Miranda D., Endeman H., Gommers D., Meuwese C., Maas J., Van Gijlswijk M. J., Van Berg R. N., Candura D., Van der Linden M., Kant M., Van der Heijden J. J., Scholten E., Van Belle-van Haren N., Lagrand W. K., Vlaar A. P., De Jong S., Cander B., Sargin M., Ugur M., Kaygin M. A., Daly K., Agnew N., Head L., Kelly L., Anoma G., Russell C., Aquino V., Scott I., Flemming L., Gillon S., Moore O., Gelandt E., Auzinger G., Patel S., and Loveridge R.

Abstract

Background: Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with COVID-19, but uncertainty remains about the determinants of in-hospital mortality and data on post-discharge outcomes are scarce. The aims of this study were to investigate the variables associated with in-hospital outcomes in patients who received ECMO during the first wave of COVID-19 and to describe the status of patients 6 months after ECMO initiation. Methods: EuroECMO-COVID is a prospective, multicentre, observational study developed by the European Extracorporeal Life Support Organization. This study was based on data from patients aged 16 years or older who received ECMO support for refractory COVID-19 during the first wave of the pandemic—from March 1 to Sept 13, 2020—at 133 centres in 21 countries. In-hospital mortality and mortality 6 months after ECMO initiation were the primary outcomes. Mixed-Cox proportional hazards models were used to investigate associations between patient and management-related variables (eg, patient demographics, comorbidities, pre-ECMO status, and ECMO characteristics and complications) and in-hospital deaths. Survival status at 6 months was established through patient contact or institutional charts review. This study is registered with ClinicalTrials.gov, NCT04366921, and is ongoing. Findings: Between March 1 and Sept 13, 2020, 1215 patients (942 [78%] men and 267 [22%] women; median age 53 years [IQR 46–60]) were included in the study. Median ECMO duration was 15 days (IQR 8–27). 602 (50%) of 1215 patients died in hospital, and 852 (74%) patients had at least one complication. Multiorgan failure was the leading cause of death (192 [36%] of 528 patients who died with available data). In mixed-Cox analyses, age of 60 years or older, use of inotropes and vasopressors before ECMO initiation, chronic renal failure, and time from intubation to ECMO initiation of 4 days or more were associated with higher in-hospital mortality. 613 patients

Published
2023

9. High-density lipoproteins (HDL) stimulate placental lactogen secretion in pregnant ewes: further evidence for a role of HDL in placental lactogen secretion during pregnancy

Author

Grandis, A., Jorgensen, V., Kodack, L., Quarfordt, S., and Handwerger, S.

Abstract

Previous studies from our laboratory showed that high-density lipoproteins (HDL) stimulate the release of human placental lactogen (PL) from cultured trophoblast cells from normal pregnant women. To determine whether HDL stimulates PL secretion in vivo, ovine HDL was infused over 2–5 min into 11 pregnant ewes (22 separate experiments) at 86–130 days of gestation via an indwelling catheter into the maternal jugular vein. The HDL, freshly prepared from the plasma of pregnant ewes by differential flotation ultracentrifugation, was greater than 99% purified as judged by SDS-PAGE. Plasma samples were obtained from the ewes before and at 0·5-h intervals for 6 h following the infusions and were assayed for PL by a specific homologous radioimmunoassay. The maternal infusion of HDL at doses of 302–784 mg (5·3–13·8 mg/kg body weight) stimulated significant increases in maternal plasma PL concentrations in six out of eight experiments (six ewes), and the infusion of 108–264 mg (1·9–4·6 mg/kg) stimulated plasma PL concentrations in two out of six experiments. In contrast, HDL at doses < 100 mg were without effect in eight experiments. The response to the HDL infusions was characterized by a sustained increase in plasma PL concentrations beginning 1·5–2·5 h after the infusions, reaching a maximum 274·2 ± 21·9% of the baseline value (P<0·001). In contrast, the maternal infusion of lipoprotein-free plasma proteins or saline had no effect on maternal plasma PL concentrations. Although the infusion of HDL into pregnant ewes stimulated an increase in maternal plasma PL concentrations, the infusion of HDL (0·8–22·0 mg/kg) into three fetuses in seven separate experiments had no effect on fetal plasma PL concentrations. The demonstration that HDL stimulates an increase in plasma PL concentrations in pregnant ewes strongly supports a novel physiological role for HDL in the regulation of PL secretion.Journal of Endocrinology(1989) 120,423–427

Published
1989
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11. Reduction in the use of benzodiazepines and cyclopyrrolones in general practice

Author

Jørgensen VR and Toft BS

Subjects
Benzodiazepines, Physician's Practice Patterns, Denmark, Therapeutics. Pharmacology, RM1-950, Pharmacy and materia medica, RS1-441
Abstract

In 2003, the Danish Minister for the Interior and Health instructed general practitioners to reduce prescriptions of benzodiazepines (BZD) and cyclopyrrolones (CP) by 50%. However, no effective methods were specified. In Denmark, it is estimated that there are approximately 100,000 BZD-dependent patients, constituting approximately 2% of the population. Objective: This article describes the implementation of a successful, simple and voluntary intervention to reduce the use of dependence-inducing drugs, while at the same time challenging practitioners' ingrained habits and prejudices in this field.Methods: The rules implemented were essentially in accordance with the official Danish rules, such that a prescription for BZD and CP could only be issued for one month at a time, and only following consultation. Use was monitored using the Danish registration system, Ordiprax, which monitors sales of prescription medicine. Two Danish general practices, comprising a patient base of approximately 2300 were studied. With the exception of the severely physically or mentally ill, all users of BZD and CP were included.Results: After 2½ years, the use of BZD and CP was reduced by 75% and 90%, respectively. The reorganization of prescription patterns was seen to be significantly easier than physicians had expected. During the first three months, only four to five additional visits per week per 1000 patients were required. Subsequently, this number was stabilized at one to two additional visits. The usual collaborative partners, such as psychiatrists, homecare services, hospitals and substance abuse units were essentially not deployed. No serious withdrawal effects arose.Conclusion: The implementation of the aforementioned simple procedures is to be recommended for the prescription of BZD and CP drugs, as the effect is immediate and easily attainable, with a reasonable work input required on the part of general practitioners.

Published
2008

12. Reducing the use of benzodiazepines and cyclopyrrolones in clinical practice

Author

Jørgensen VR, Toft BS, and Fogh MS

Subjects
Benzodiazepines, Cyclopyrrolones, Substance-related disorders, Adverse effects, Denmark., Therapeutics. Pharmacology, RM1-950, Pharmacy and materia medica, RS1-441
Abstract

Objective: Recently, the use of benzodiazepines (BZD) and cyclopyrrolones (CP) has drawn a great deal of attention. About 100,000 patients - approximately 2% of the Danish population - are believed to be addicted to BZD. This article describes a simple and effective method of reducing the use of dependency-producing drugs in clinical practice. Methods: Design: Local rules were implemented according to Danish directive CIR nr 12 13/01/2003 regarding addictive drugs. Prescriptions for BZD and CP were only issued on a monthly basis, and only following personal consultation. This monthly requirement forced the physician as well as the patient to evaluate whether the existing prescription pattern was indicated, or whether a drug-reducing regime should be introduced. The prescription pattern was monitored using the Ordiprax System (Institute for Rational Pharmacotherapy, IRF), which records pharmacy's sales of prescription drugs as prescribed by clinical practices. Two individual clinics in Thyborøn - Harboøre Community, covering some 2300 patients, were surveyed. All patients using BZD or CP were included in this study, with the exception of patients suffering from serious psychiatric or physical disorders. Results: After 15 months, the use of BZD and CP was reduced by 50% and 75%, respectively. The process of changing prescription habits was far easier than expected. A whole group of patients, initially invisible to the physician, was exposed. During the first three months, as few as 4-5 additional consultations for every 1000 patients was required. There was essentially no need for assistance from our usual partners, including psychiatrists, hospitals, specialist units for addictive treatment. Conclusion: We strongly recommend that these simple procedures be incorporated into daily routine when prescribing either a BD or a CP.

Published
2006

13. Proteome asymmetry in mouse and human embryos before fate specification.

Author

Iwamoto-Stohl LK, Petelski AA, Meglicki M, Fu A, Khan S, Specht H, Huffman G, Derks J, Jorgensen V, Weatherbee BAT, Weberling A, Gantner CW, Mandelbaum RS, Paulson RJ, Lam L, Ahmady A, Vasquez ES, Slavov N, and Zernicka-Goetz M

Abstract

Pre-patterning of the embryo, driven by spatially localized factors, is a common feature across several non-mammalian species 1-4 . However, mammals display regulative development and thus it was thought that blastomeres of the embryo do not show such pre-patterning, contributing randomly to the three lineages of the blastocyst: the epiblast, primitive endoderm and trophectoderm that will generate the new organism, the yolk sac and placenta respectively 4-6 . Unexpectedly, early blastomeres of mouse and human embryos have been reported to have distinct developmental fates, potential and heterogeneous abundance of certain transcripts 7-12 . Nevertheless, the extent of the earliest intra-embryo differences remains unclear and controversial. Here, by utilizing multiplexed and label-free single-cell proteomics by mass-spectrometry 13 , we show that 2-cell mouse and human embryos contain an alpha and a beta blastomere as defined by differential abundance of hundreds of proteins exhibiting strong functional enrichment for protein synthesis, transport, and degradation. Such asymmetrically distributed proteins include Gps1 and Nedd8, depletion or overexpression of which in one blastomere of the 2-cell embryo impacts lineage segregation. These protein asymmetries increase at 4-cell stage. Intriguingly, halved mouse zygotes display asymmetric protein abundance that resembles alpha and beta blastomeres, suggesting differential proteome localization already within zygotes. We find that beta blastomeres give rise to a blastocyst with a higher proportion of epiblast cells than alpha blastomeres and that vegetal blastomeres, which are known to have a reduced developmental potential, are more likely to be alpha. Human 2-cell blastomeres also partition into two clusters sharing strong concordance with clusters found in mouse, in terms of differentially abundant proteins and functional enrichment. To our knowledge, this is the first demonstration of intra-zygotic and inter-blastomere proteomic asymmetry in mammals that has a role in lineage segregation.

Published
2024
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14. Topical section: embryonic models (2023) for Current Opinion in Genetics & Development.

Author

Handford CE, Junyent S, Jorgensen V, and Zernicka-Goetz M

Subjects
Animals, Female, Pregnancy, Organogenesis, Stem Cells, Mammals, Embryonic Development genetics, Embryo, Mammalian
Abstract

Stem cell-based mammalian embryo models facilitate the discovery of developmental mechanisms because they are more amenable to genetic and epigenetic perturbations than natural embryos. Here, we highlight exciting recent advances that have yielded a plethora of models of embryonic development. Imperfections in these models highlight gaps in our current understanding and outline future research directions, ushering in an exciting new era for embryology., Competing Interests: Declaration of Competing Interest The authors are inventors on the following patents: 1. Patent applicant: Caltech. Inventors: Magdalena Zernicka-Goetz, Berna Sozen, and Victoria Jorgensen. Application number: 17/692,790. Specific aspect of the paper covered in patent application: Reconstructing human early embryogenesis in vitro with pluripotent stem cells. 2. Patent applicant: Caltech and Cambridge Enterprise Limited. Inventors: Magdalena Zernicka-Goetz, Gianluca Amadei, and Charlotte Handford. Application number: 63/397,630. Specific aspect of the paper covered in patent application: Synthetic embryos. 3. Patent Applicant: Caltech and Cambridge Enterprise Limited. Inventors: Magdalena Zernicka-Goetz, Bailey Weatherbee, and Carlos Gantner. Application number: 63/403,684. Specific aspect of the paper covered in patent application: Stem cell-derived model of the human embryo., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Published
2024
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15. Early and intensive motor training to enhance neurological recovery in people with spinal cord injury: trial protocol.

Author

Harvey LA, Glinsky JV, Chu J, Herbert RD, Liu H, Jan S, Billot L, Scivoletto G, Spooren AI, Seelen HA, Ben M, Tranter K, Chen LW, Rainey D, Rimmer C, Jorgensen V, Di Natal F, Denis S, Gollan EJ, Tamburella F, Agostinello J, van Laake-Geelen CM, Bell C, Lincoln C, Stolwijk JM, van der Lede J, Paddison S, Oostra K, Cameron ID, Weber G, Sherrington C, Nunn AK, Synnott EL, McCaughey E, Kaur J, and Shetty S

Subjects
Humans, Quality of Life, Treatment Outcome, Recovery of Function, Walking, Randomized Controlled Trials as Topic, Multicenter Studies as Topic, Spinal Cord Injuries
Abstract

Study Design: Protocol for a multi-centre randomised controlled trial (the SCI-MT trial)., Objectives: To determine whether 10 weeks of intensive motor training enhances neurological recovery in people with recent spinal cord injury (SCI)., Setting: Fifteen spinal injury units in Australia, Scotland, England, Italy, Netherlands, Norway, and Belgium., Methods: A pragmatic randomised controlled trial will be undertaken. Two hundred and twenty people with recent SCI (onset in the preceding 10 weeks, American Spinal Injuries Association Impairment Scale (AIS) A lesion with motor function more than three levels below the motor level on one or both sides, or an AIS C or D lesion) will be randomised to receive either usual care plus intensive motor training (12 h of motor training per week for 10 weeks) or usual care alone. The primary outcome is neurological recovery at 10 weeks, measured with the Total Motor Score from the International Standards for Neurological Classification of SCI. Secondary outcomes include global measures of motor function, ability to walk, quality of life, participants' perceptions about ability to perform self-selected goals, length of hospital stay and participants' impressions of therapeutic benefit at 10 weeks and 6 months. A cost-effectiveness study and process evaluation will be run alongside the trial. The first participant was randomised in June 2021 and the trial is due for completion in 2025., Conclusions: The findings of the SCI-MT Trial will guide recommendations about the type and dose of inpatient therapy that optimises neurological recovery in people with SCI., Trial Registration: ACTRN12621000091808 (1.2.2021)., (© 2023. The Author(s).)

Published
2023
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16. Perioperative pressure injury prevention: National Pressure Injury Advisory Panel root cause analysis toolkit 3.0.

Author

Tescher A, Deppisch M, Munro C, Jorgensen V, and Cuddigan J

Subjects
Humans, Perioperative Care, Root Cause Analysis, Pressure Ulcer prevention & control
Abstract

Objectives: Operating room-related pressure injuries (ORPI) are particularly challenging to examine for several reasons. Time in the OR is often a distinct event within the hospitalisation, and discovery of an ORPI may occur between several hours and up to 5 days postoperatively. The National Pressure Injury Advisory Panel (NPIAP) first developed a root cause analysis (RCA) toolkit in 2017 as a systematic strategy for investigating the root causes of facility-acquired pressure injury (PI). The purpose of this 2021 RCA toolkit update was to address an expanded investigation of medical device-related PIs (MDRPIs), both inside and outside the OR, as well as the specific PI prevention issues of the perioperative area., Methods: Clinicians have been using the 2017 toolkit as a basis for ongoing quality improvement tracking, since it provides more accurate information than data extractions from patient health records. A small working group consisting of NPIAP board and panel members developed investigative questions to identify the ORPI root causes and compliance with best practices for the entire perioperative experience., Results: Action items are linked to evidence-based recommendations from the NPIAP/European Pressure Ulcer Advisory Panel/Pan Pacific Pressure Injury Alliance 2019 International Guideline and the Association of PeriOperative Registered Nurses (AORN) Guidelines for Perioperative Practice. A multidisciplinary clinician guide was also developed to identify practice gaps and to compile the information into an action plan for staff education and/or process improvement., Conclusion: The updated NPIAP RCA toolkit provides mechanisms for investigating, compiling and trending data as a basis for data-driven quality improvement. Using the enhanced investigative tools, the root causes of both MDRPIs and ORPIs can be better understood to target efforts to reduce their occurrence.

Published
2022
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17. Reconstructing aspects of human embryogenesis with pluripotent stem cells.

Author

Sozen B, Jorgensen V, Weatherbee BAT, Chen S, Zhu M, and Zernicka-Goetz M

Subjects
Adaptor Proteins, Signal Transducing genetics, Adaptor Proteins, Signal Transducing metabolism, Biomarkers metabolism, Blastocyst metabolism, Cell Lineage genetics, Embryo, Mammalian anatomy & histology, Embryo, Mammalian metabolism, GATA3 Transcription Factor genetics, GATA3 Transcription Factor metabolism, Gene Expression, Humans, Phospholipase C beta genetics, Phospholipase C beta metabolism, Pluripotent Stem Cells metabolism, SOXB1 Transcription Factors genetics, SOXB1 Transcription Factors metabolism, SOXF Transcription Factors genetics, SOXF Transcription Factors metabolism, Sequence Analysis, RNA, Single-Cell Analysis, Blastocyst cytology, Cell Culture Techniques, Embryo, Mammalian cytology, Embryonic Development genetics, Models, Biological, Pluripotent Stem Cells cytology
Abstract

Understanding human development is of fundamental biological and clinical importance. Despite its significance, mechanisms behind human embryogenesis remain largely unknown. Here, we attempt to model human early embryo development with expanded pluripotent stem cells (EPSCs) in 3-dimensions. We define a protocol that allows us to generate self-organizing cystic structures from human EPSCs that display some hallmarks of human early embryogenesis. These structures mimic polarization and cavitation characteristic of pre-implantation development leading to blastocyst morphology formation and the transition to post-implantation-like organization upon extended culture. Single-cell RNA sequencing of these structures reveals subsets of cells bearing some resemblance to epiblast, hypoblast and trophectoderm lineages. Nevertheless, significant divergences from natural blastocysts persist in some key markers, and signalling pathways point towards ways in which morphology and transcriptional-level cell identities may diverge in stem cell models of the embryo. Thus, this stem cell platform provides insights into the design of stem cell models of embryogenesis., (© 2021. The Author(s).)

Published
2021
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18. Integrated genomic analysis reveals key features of long undecoded transcript isoform-based gene repression.

Author

Tresenrider A, Morse K, Jorgensen V, Chia M, Liao H, van Werven FJ, and Ünal E

Subjects
Chromatin metabolism, Genes, Reporter, Meiosis genetics, Nanopore Sequencing, Nucleosomes metabolism, Open Reading Frames genetics, Promoter Regions, Genetic genetics, Prophase genetics, Protein Biosynthesis genetics, Protein Isoforms genetics, Protein Isoforms metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Transcription Factors metabolism, Transcription, Genetic, Gene Expression Regulation, Fungal, Genomics, Saccharomyces cerevisiae genetics
Abstract

Long undecoded transcript isoforms (LUTIs) represent a class of non-canonical mRNAs that downregulate gene expression through the combined act of transcriptional and translational repression. While single gene studies revealed important aspects of LUTI-based repression, how these features affect gene regulation on a global scale is unknown. Using transcript leader and direct RNA sequencing, here, we identify 74 LUTI candidates that are specifically induced in meiotic prophase. Translational repression of these candidates appears to be ubiquitous and is dependent on upstream open reading frames. However, LUTI-based transcriptional repression is variable. In only 50% of the cases, LUTI transcription causes downregulation of the protein-coding transcript isoform. Higher LUTI expression, enrichment of histone 3 lysine 36 trimethylation, and changes in nucleosome position are the strongest predictors of LUTI-based transcriptional repression. We conclude that LUTIs downregulate gene expression in a manner that integrates translational repression, chromatin state changes, and the magnitude of LUTI expression., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2021
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19. Tunable Transcriptional Interference at the Endogenous Alcohol Dehydrogenase Gene Locus in Drosophila melanogaster .

Author

Jorgensen V, Chen J, Vander Wende H, Harris DE, McCarthy A, Breznak S, Wong-Deyrup SW, Chen Y, Rangan P, Brar GA, Sawyer EM, Chan LY, and Ünal E

Subjects
Animals, Drosophila genetics, Promoter Regions, Genetic, Transcription, Genetic, Alcohol Dehydrogenase genetics, Drosophila melanogaster genetics
Abstract

Neighboring sequences of a gene can influence its expression. In the phenomenon known as transcriptional interference, transcription at one region in the genome can repress transcription at a nearby region in cis Transcriptional interference occurs at a number of eukaryotic loci, including the alcohol dehydrogenase ( Adh ) gene in Drosophila melanogaster Adh is regulated by two promoters, which are distinct in their developmental timing of activation. It has been shown using transgene insertion that when the promoter distal from the Adh start codon is deleted, transcription from the proximal promoter becomes de-regulated. As a result, the Adh proximal promoter, which is normally active only during the early larval stages, becomes abnormally activated in adults. Whether this type of regulation occurs in the endogenous Adh context, however, remains unclear. Here, we employed the CRISPR/Cas9 system to edit the endogenous Adh locus and found that removal of the distal promoter also resulted in the untimely expression of the proximal promoter-driven mRNA isoform in adults, albeit at lower levels than previously reported. Importantly, transcription from the distal promoter was sufficient to repress proximal transcription in larvae, and the degree of this repression was dependent on the degree of distal promoter activity. Finally, upregulation of the distal Adh transcript led to the enrichment of histone 3 lysine 36 trimethylation over the Adh proximal promoter. We conclude that the endogenous Adh locus is developmentally regulated by transcriptional interference in a tunable manner., (Copyright © 2020 Jorgensen et al.)

Published
2020
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20. Evidence for an Integrated Gene Repression Mechanism Based on mRNA Isoform Toggling in Human Cells.

Author

Hollerer I, Barker JC, Jorgensen V, Tresenrider A, Dugast-Darzacq C, Chan LY, Darzacq X, Tjian R, Ünal E, and Brar GA

Subjects
CRISPR-Cas Systems, Chromatin Immunoprecipitation, Gene Knockdown Techniques, Histones metabolism, Humans, MCF-7 Cells, Promoter Regions, Genetic, Gene Expression Regulation, Models, Genetic, Proto-Oncogene Proteins c-mdm2 genetics
Abstract

We recently described an unconventional mode of gene regulation in budding yeast by which transcriptional and translational interference collaborate to down-regulate protein expression. Developmentally timed transcriptional interference inhibited production of a well translated mRNA isoform and resulted in the production of an mRNA isoform containing inhibitory upstream open reading frames (uORFs) that prevented translation of the main ORF. Transcriptional interference and uORF-based translational repression are established mechanisms outside of yeast, but whether this type of integrated regulation was conserved was unknown. Here we find that, indeed, a similar type of regulation occurs at the locus for the human oncogene MDM2 We observe evidence of transcriptional interference between the two MDM2 promoters, which produce a poorly translated distal promoter-derived uORF-containing mRNA isoform and a well-translated proximal promoter-derived transcript. Down-regulation of distal promoter activity markedly up-regulates proximal promoter-driven expression and results in local reduction of histone H3K36 trimethylation. Moreover, we observe that this transcript toggling between the two MDM2 isoforms naturally occurs during human embryonic stem cell differentiation programs., (Copyright © 2019 Hollerer et al.)

Published
2019
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21. Developmental regulation of an organelle tether coordinates mitochondrial remodeling in meiosis.

Author

Sawyer EM, Joshi PR, Jorgensen V, Yunus J, Berchowitz LE, and Ünal E

Subjects
DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Mitochondria genetics, Phosphorylation physiology, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins genetics, Saccharomyces cerevisiae Proteins metabolism, Transcription Factors genetics, Transcription Factors metabolism, Meiosis physiology, Mitochondria metabolism, Mitochondrial Dynamics physiology, Saccharomyces cerevisiae metabolism
Abstract

Cellular differentiation involves remodeling cellular architecture to transform one cell type to another. By investigating mitochondrial dynamics during meiotic differentiation in budding yeast, we sought to understand how organelle morphogenesis is developmentally controlled in a system where regulators of differentiation and organelle architecture are known, but the interface between them remains unexplored. We analyzed the regulation of mitochondrial detachment from the cell cortex, a known meiotic alteration to mitochondrial morphology. We found that mitochondrial detachment is enabled by the programmed destruction of the mitochondria-endoplasmic reticulum-cortex anchor (MECA), an organelle tether that bridges mitochondria and the plasma membrane. MECA regulation is governed by a meiotic transcription factor, Ndt80, which promotes the activation of a conserved kinase, Ime2. We further present evidence for Ime2-dependent phosphorylation and degradation of MECA in a temporally controlled manner. Our study defines a key mechanism that coordinates mitochondrial morphogenesis with the landmark events of meiosis and demonstrates that cells can developmentally regulate tethering to induce organelle remodeling., (© 2019 Sawyer et al.)

Published
2019
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22. Transcription of a 5' extended mRNA isoform directs dynamic chromatin changes and interference of a downstream promoter.

Author

Chia M, Tresenrider A, Chen J, Spedale G, Jorgensen V, Ünal E, and van Werven FJ

Subjects
Kinetochores metabolism, Promoter Regions, Genetic, Chromatin metabolism, Gene Expression Regulation, Fungal, Meiosis, Nuclear Proteins biosynthesis, RNA Isoforms biosynthesis, Saccharomyces cerevisiae physiology, Saccharomyces cerevisiae Proteins biosynthesis, Transcription, Genetic
Abstract

Cell differentiation programs require dynamic regulation of gene expression. During meiotic prophase in Saccharomyces cerevisiae , expression of the kinetochore complex subunit Ndc80 is downregulated by a 5' extended long undecoded NDC80 transcript isoform. Here we demonstrate a transcriptional interference mechanism that is responsible for inhibiting expression of the coding NDC80 mRNA isoform. Transcription from a distal NDC80 promoter directs Set1-dependent histone H3K4 dimethylation and Set2-dependent H3K36 trimethylation to establish a repressive chromatin state in the downstream canonical NDC80 promoter. As a consequence, NDC80 expression is repressed during meiotic prophase. The transcriptional mechanism described here is rapidly reversible, adaptable to fine-tune gene expression, and relies on Set2 and the Set3 histone deacetylase complex. Thus, expression of a 5' extended mRNA isoform causes transcriptional interference at the downstream promoter. We demonstrate that this is an effective mechanism to promote dynamic changes in gene expression during cell differentiation.

Published
2017
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23. Kinetochore inactivation by expression of a repressive mRNA.

Author

Chen J, Tresenrider A, Chia M, McSwiggen DT, Spedale G, Jorgensen V, Liao H, van Werven FJ, and Ünal E

Subjects
Nuclear Proteins genetics, Protein Biosynthesis, RNA Isoforms genetics, Saccharomyces cerevisiae Proteins genetics, Transcription, Genetic, Gene Expression Regulation, Fungal, Kinetochores metabolism, Meiosis, Nuclear Proteins biosynthesis, RNA Isoforms biosynthesis, Saccharomyces cerevisiae physiology, Saccharomyces cerevisiae Proteins biosynthesis
Abstract

Differentiation programs such as meiosis depend on extensive gene regulation to mediate cellular morphogenesis. Meiosis requires transient removal of the outer kinetochore, the complex that connects microtubules to chromosomes. How the meiotic gene expression program temporally restricts kinetochore function is unknown. We discovered that in budding yeast, kinetochore inactivation occurs by reducing the abundance of a limiting subunit, Ndc80. Furthermore, we uncovered an integrated mechanism that acts at the transcriptional and translational level to repress NDC80 expression. Central to this mechanism is the developmentally controlled transcription of an alternate NDC80 mRNA isoform, which itself cannot produce protein due to regulatory upstream ORFs in its extended 5' leader. Instead, transcription of this isoform represses the canonical NDC80 mRNA expression in cis , thereby inhibiting Ndc80 protein synthesis. This model of gene regulation raises the intriguing notion that transcription of an mRNA, despite carrying a canonical coding sequence, can directly cause gene repression.

Published
2017
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24. Triphenylphosphine oxide is a potent and selective inhibitor of the transient receptor potential melastatin-5 ion channel.

Author

Palmer RK, Atwal K, Bakaj I, Carlucci-Derbyshire S, Buber MT, Cerne R, Cortés RY, Devantier HR, Jorgensen V, Pawlyk A, Lee SP, Sprous DG, Zhang Z, and Bryant R

Subjects
Animals, Calcium metabolism, HEK293 Cells, Humans, Ion Channel Gating drug effects, Luminescent Measurements, Membrane Potentials drug effects, Mice, Mice, Transgenic, Organophosphorus Compounds chemistry, Patch-Clamp Techniques, Structure-Activity Relationship, TRPM Cation Channels genetics, Taste, Taste Buds drug effects, Taste Buds physiology, Organophosphorus Compounds pharmacology, TRPM Cation Channels antagonists & inhibitors
Abstract

Transient receptor potential melastatin-5 (TRPM5) is a calcium-gated monovalent cation channel expressed in highly specialized cells of the taste bud and gastrointestinal tract, as well as in pancreatic β-cells. Well established as a critical signaling protein for G protein-coupled receptor-mediated taste pathways, TRPM5 also has recently been implicated as a regulator of incretin and insulin secretion. To date, no inhibitors of practical use have been described that could facilitate investigation of TRPM5 functions in taste or secretion of metabolic hormones. Using recombinant TRPM5-expressing cells in a fluorescence imaging plate reader-based membrane potential assay, we identified triphenylphosphine oxide (TPPO) as a selective and potent inhibitor of TRPM5. TPPO inhibited both human (IC₅₀ = 12 μM) and murine TRPM5 (IC₅₀ = 30 μM) heterologously expressed in HEK293 cells, but had no effect (up to 100 μM) on the membrane potential responses of TRPA1, TRPV1, or TRPM4b. TPPO also inhibited a calcium-gated TRPM5-dependent conductance in taste cells isolated from the tongues of transgenic TRPM5(+/)⁻ mice. In contrast, TPP had no effect on TRPM5 responses, indicating a strict requirement of the oxygen atom for activity. Sixteen additional TPPO derivatives also inhibited TRPM5 but none more potently than TPPO. Structure-activity relationship of tested compounds was used for molecular modeling-based analysis to clarify the positive and negative structural contributions to the potency of TPPO and its derivatives. TPPO is the most potent TRPM5 inhibitor described to date and is the first demonstrated to exhibit selectivity over other channels.

Published
2010
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25. Comprehensive training for hazard communication.

Author

Cuny E, Jorgensen V, and Galligan J

Subjects
Communication, Humans, Occupational Exposure prevention & control, Teaching, United States, Guidelines as Topic, Hazardous Substances, Occupational Exposure legislation & jurisprudence, Safety Management, United States Occupational Safety and Health Administration legislation & jurisprudence
Abstract

Long before the Bloodborne Pathogens Standard caught the attention of the dental profession, the Occupational Safety and Health Administration required all employers to collect information about hazardous chemicals in the workplace and provide information and training to employees regarding the materials. The Hazard Communication Standard requires employers to establish written programs, collect specific information regarding workplace chemicals, and conduct a formal training program for employees.

Published
2005

26. Women doctors campaign against female circumcision.

Author

Jorgensen V

Subjects
Africa, Africa South of the Sahara, Africa, Eastern, Ambulatory Care Facilities, Demography, Denmark, Developed Countries, Developing Countries, Europe, Health Planning, Middle East, Organization and Administration, Population, Population Dynamics, Scandinavian and Nordic Countries, Somalia, Transients and Migrants, Counseling, Emigration and Immigration, Evaluation Studies as Topic, Refugees
Published
1998

30. Effect of insulin, proinsulin and pancreatic extract on myelination and remyelination in organotypic nerve tissue in culture.

Author

Roth GA, Jorgensen VH, and Bornstein MB

Subjects
2',3'-Cyclic Nucleotide 3'-Phosphodiesterase, 2',3'-Cyclic-Nucleotide Phosphodiesterases metabolism, Animals, Culture Media, Culture Techniques, Embryo, Mammalian, Female, Mice, Myelin Sheath drug effects, Myelin Sheath enzymology, Nerve Fibers, Myelinated physiology, Nerve Tissue drug effects, Nerve Tissue enzymology, Spinal Cord, Insulin pharmacology, Myelin Sheath physiology, Nerve Tissue physiology, Pancreatic Extracts pharmacology, Phosphoric Diester Hydrolases, Proinsulin pharmacology
Abstract

The effect of insulin, proinsulin and crude pancreatic extract was studied in organotypic nerve tissue cultures, principally in relation to the development of myelin. Cultures were exposed to media supplemented with these substances beginning on the first day of explantation. By 4 days in vitro, there was a good neuritic outgrowth from all the fragments. That from the insulin and pancreatic extract-fed were more profuse and extended further than from the control group. By 8-12 days in vitro it was also possible to observe more myelinated axons in these treated groups. The pattern of changes in the myelin associated enzyme activity, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) paralleled the differential increase in myelination. Insulin-fed cultures showed a more rapid increase in CNPase activity, which, after 21 days in vitro reached a plateau about 30-50% over that of the controls. Cultures treated with pancreatic extract showed a similar pattern of increased activity, while in proinsulin-treated explants the activity was only significantly higher after 21 days in vitro. To study the effect of these substances on remyelination, well myelinated cultures were completely demyelinated by exposure to anti-white matter antiserum and were subsequently exposed to the same normal control or supplemented media. The amount of myelin and concomitantly the CNPase activity increased rapidly and in the same proportion between the various groups as was observed previously during primary myelination. Insulin as well as crude pancreatic extract and, to some extent, proinsulin demonstrated a marked effect on the time of onset and principally on the total amount of myelin developed by treated cultures as compared to those maintained in normal nutrient medium.

Published
1985
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38. One-year contraceptive follow-up of adolescent patients.

Author

Jorgensen V

Subjects
Adolescent, Child, Contraceptive Devices adverse effects, Contraceptives, Oral adverse effects, Counseling, Family Planning Services, Female, Follow-Up Studies, Humans, Hypertension chemically induced, Intrauterine Devices, Peer Group, Pennsylvania, Postpartum Period, Pregnancy, Contraception
Published
1973
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39. [Complications following periodontal surgery].

Author

Boysen H, Jorgensen VA, and Loe H

Subjects
Female, Humans, Male, Pain etiology, Postoperative Complications, Time Factors, Gingivectomy adverse effects, Periodontal Diseases surgery
Published
1972

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