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7. Sprague Dawley rats from different vendors vary in the modulation of prepulse inhibition of startle (PPI) by dopamine, acetylcholine, and glutamate drugs

Author

Caine, S. B., Plant, S., Furbish, K., Yerton, M., Smaragdi, E., Niclou, B., Lorusso, J. M., Chang, J. Y., Bitter, C., Basu, A., Miller, S., Huang, C. Y., Komson, R., Liu, D., Behar, S., Thomsen, M., Caine, S. B., Plant, S., Furbish, K., Yerton, M., Smaragdi, E., Niclou, B., Lorusso, J. M., Chang, J. Y., Bitter, C., Basu, A., Miller, S., Huang, C. Y., Komson, R., Liu, D., Behar, S., and Thomsen, M.

Abstract

Rationale Rodent vendors are often utilized interchangeably, assuming that the phenotype of a given strain remains standardized between colonies. Several studies, however, have found significant behavioral and physiological differences between Sprague Dawley (SD) rats from separate vendors. Prepulse inhibition of startle (PPI), a form of sensorimotor gating in which a low-intensity leading stimulus reduces the startle response to a subsequent stimulus, may also vary by vendor. Differences in PPI between rat strains are well known, but divergence between colonies within the SD strain lacks thorough examination. Objectives We explored intrastrain variation in PPI by testing SD rats from two vendors: Envigo and Charles River (CR). Methods We selected drugs acting on four major neurotransmitter systems that have been repeatedly shown to modulate PPI: dopamine (apomorphine; 0.5, 1.5, 3.0 mg/kg), acetylcholine (scopolamine; 0.1, 0.5, 1.0 mg/kg), glutamate (dizocilpine; 0.5, 1.5, 2.5 mg/kg), and serotonin (2,5-Dimethoxy-4-iodoamphetamine, DOI; 0.25, 0.5, 1.0 mg/kg). We determined PPI and startle amplitude for each drug in male and female Envigo and CR SD rats. Results SD rats from Envigo showed dose-dependent decreases in PPI after apomorphine, scopolamine, or dizocilpine administration, without significant effects on startle amplitude. SD rats from CR were less sensitive to modulation of PPI and/or more sensitive to modulation of startle amplitude, across the three drugs. Conclusions SD rats showed vendor differences in sensitivity to pharmacological modulation of PPI and startle. We encourage researchers to sample rats from separate vendors before experimentation to identify the most suited source of subjects for their specific endpoints., Rationale: Rodent vendors are often utilized interchangeably, assuming that the phenotype of a given strain remains standardized between colonies. Several studies, however, have found significant behavioral and physiological differences between Sprague Dawley (SD) rats from separate vendors. Prepulse inhibition of startle (PPI), a form of sensorimotor gating in which a low-intensity leading stimulus reduces the startle response to a subsequent stimulus, may also vary by vendor. Differences in PPI between rat strains are well known, but divergence between colonies within the SD strain lacks thorough examination. Objectives: We explored intrastrain variation in PPI by testing SD rats from two vendors: Envigo and Charles River (CR). Methods: We selected drugs acting on four major neurotransmitter systems that have been repeatedly shown to modulate PPI: dopamine (apomorphine; 0.5, 1.5, 3.0 mg/kg), acetylcholine (scopolamine; 0.1, 0.5, 1.0 mg/kg), glutamate (dizocilpine; 0.5, 1.5, 2.5 mg/kg), and serotonin (2,5-Dimethoxy-4-iodoamphetamine, DOI; 0.25, 0.5, 1.0 mg/kg). We determined PPI and startle amplitude for each drug in male and female Envigo and CR SD rats. Results: SD rats from Envigo showed dose-dependent decreases in PPI after apomorphine, scopolamine, or dizocilpine administration, without significant effects on startle amplitude. SD rats from CR were less sensitive to modulation of PPI and/or more sensitive to modulation of startle amplitude, across the three drugs. Conclusions: SD rats showed vendor differences in sensitivity to pharmacological modulation of PPI and startle. We encourage researchers to sample rats from separate vendors before experimentation to identify the most suited source of subjects for their specific endpoints.

Published
2023

8. Estimated GFR and the Effect of Intensive Blood Pressure Lowering After Acute Intracerebral Hemorrhage

Author

Anderson, C.S., Chalmers, J., Arima, H., Davis, S., Heeley, E., Huang, Y., Lavados, P., Neal, B., Parsons, M.W., Lindley, R., Morgenstern, L., Robinson, T., Stapf, C., Tzourio, C., Wang, J.G., Chen, S., Chen, X.Y., Cui, L., Liu, Z., Lu, C., Wang, J., Wu, S., Xu, E., Yang, Q., Zhang, C., Zhang, J., Beer, R., Schmutzhard, E., Redondo, P., Kaste, M., Soinne, L., Tatlisumak, T., Wartenberg, K., Ricci, S., Klijn, K., Azevedo, E., Chamorro, A., Arnold, M., Fischer, U., Kaul, S., Pandian, J., Boyini, H., Singh, S., Rabinstein, A.A., Estol, C., Silva, G., Olavarria, V.V., Robinson, T.G., Simes, R.J., Bousser, M.-G., Hankey, G., Jamrozik, K., Johnston, S.C., Li, S., Bailey, K., Cheung, T., Delcourt, C., Chintapatla, S., Ducasse, E., Erho, T., Hata, J., Holder, B., Knight, E., Leroux, M., Sassé, T., Odgers, E., Walsh, R., Wolfowicz, Z., Chen, G., Fuentes, S., Peng, B., Schneble, H.-M., Wang, M.-X., Billot, L., Heritier, S., Li, Q., Woodward, M., Abimbola, S., Anderson, S., Chan, E., Cheng, G., Chmielnik, P., Leighton, S., Liu, J.-Y., Rasmussen, B., Saxena, A., Tripathy, S., Armenis, M., Baig, M.A., Naidu, B., Starzec, G., Steley, S., Moles, A., Ruiz, A., Zimmermann, M., Marinho, J., Alves, S., Angelim, R., Araujo, J., Kawakami, L., Bustos, C., Gonzalez, F., Munoz Venturelli, P., Chen, X., Jia, R., Li, N., Qu, S., Shu, Y., Song, A., Sun, J., Xiao, J., Zhao, Y., Huang, Q., Vicaut, E., Chamam, A., Viaud, M.-C., Dert, C., Fiedler, U., Jovis, V., Kabla, S., Marchand, S., Pena, A., Rochaud, V., Mallikarjuna, K., Hasan, N., Berge, E., Sandset, E.C., Forårsveen, A.S., Richardson, D., Kumar, T., Lewin, S., Poulter, N., Field, J., Anjum, A., Wilson, A., Perelmuter, H., Agarie, A.M., Barboza, A.G., Recchia, L.A., Miranda, I.F., Rauek, S.G., Duplessis, R.J., Dewey, H., Walker, L., Petrolo, S., Bladin, C., Sturm, J., Crimmins, D., Griffiths, D., Schutz, A., Zenteno, V., Miteff, F., Spratt, N., Kerr, E., Levi, C.R., Phan, T.G., Ma, H., Sanders, L., Moran, C., Wong, K., Read, S., Henderson, R., Wong, A., Hull, R., Skinner, G., Hand, P., Yan, B., Tu, H., Campbell, B., Blacker, D.J., Wijeratne, T., Pathirage, M., Jasinararchchi, M., Matkovic, Z., Celestino, S., Gruber, F., Vosko, M.R., Diabl, E., Rathmaier, S., Pfausler, B., Helbok, R., Fazekas, F., Fischer, R., Poltrum, B., Zechner, B., Trummer, U., Rutgers, M.P., Peeters, A., Dusart, A., Duray, M.-C., Parmentier, C., Ferrao-Santos, S., Brouns, R., De Raedt, S., De Smedt, A., VanHooff, R.-J., De Keyser, J., Martins, S.C.O., de Almeida, A.G., Broudani, R., Titton, N.F., de Freitas, G.R., Cardoso, F.M., Giesel, L.M., Lima, N.A., Jr, Ferraz de Almeida, A.C., Gomes, R.B., Borges dos Santos, T.S., Veloso Soares, E.M., Neto, O.L.A., Silva, G.S., Gomes, D.L., de Carvalho, F.A., Miranda, M., Marques, A., Zétola, V.F., de Matia, G., Lange, M.C., Montes, J., Reccius, A., Soto, A., Rivas, R., Klapp, C., Illanes, S., Aguilera, C., Castro, A., Figueroa, C., Benavides, J., Salamanca, P., Concha, M.C., Pajarito, J., Araya, P., Guerra, F., Li, Y., Liu, G., Wang, B., Chong, Y., He, M., Wang, L., Liu, J., Zhang, X., Lai, C., Jiang, H., Cui, S., Tao, Q., Zhang, Y., Yao, S., Xu, M., Xiao, H., Hu, J., Tang, J., Ji, H., Jiang, M., Yu, F., Yang, X., Guo, X., Wang, Y., Wu, L., Gao, Y., Sun, D., Huang, X., Liu, L., Li, P., Jiang, Y., Li, H., Lu, H., Zhou, J., Yuan, C., Qi, X., Qiu, F., Qian, H., Wang, W., Sun, W., Li, F., Liu, R., Peng, Q., Ren, Z., Fan, C., Wang, H., Wang, T., Shi, F., Duan, C., Chen, Z., Tan, X., Zhao, Z., Chen, J., Han, T., Zhang, L., Hu, Q., Hou, Q., Zhao, X., Zeng, G., Ma, L., Wang, F., Zeng, L., Guo, Z., Fu, Y., Song, Y., Tai, L., Liu, X., Su, X., Yang, Y., Dong, R., Xu, Y., Tian, S., Cheng, S., Su, L., Xie, X., Xu, T., Geng, D., Yan, X., Fan, H., Zhao, N., Wang, S., Yang, J., Yan, M., Li, L., Li, Z., Xu, X., Lian, Y., Sun, H., Liu, D., Wang, N., Tang, Q., Han, Z., Feng, L., Cui, Y., Tian, J., Chang, H., Sun, X., Liu, C., Wen, Z., Lin, Q., Sun, L., Hu, B., Zou, M., Bao, Q., Lin, X., Zhao, L., Tian, X., Wang, X., Li, X., Hao, L., Duan, Y., Wang, R., Wei, Z., Ren, S., Ren, H., Dong, Y., Cheng, Y., Liu, W., Han, J., Zhang, Z., Zhu, J., Qian, J., Sun, Y., Liu, K., Long, F., Peng, X., Zhang, Q., Yuan, Z., Wang, C., Huang, M., He, P., You, Y., Xia, J., Zhou, L., Hou, Y., Qi, Y., Mei, L., Lu, R., Ping, L., Zhou, S., Zhang, S., Zou, R., Guo, J., Li, M., Wei, W., Curtze, S., Saarela, M., Strbian, D., Scheperjans, F., De Broucker, T., Henry, C., Cumurciuc, R., Ibos-Augé, N., Zéghoudi, A.-C., Pico, F., Dereeper, O., Simian, M.-C., Boisselier, C., Mahfoud, A., Timsit, S., Merrien, F.M., Guillon, B., Sevin, M., Herisson, F., Magne, C., Ameri, A., Cret, C., Stefanizzi, S., Klapzcynski, F., Denier, C., Sarov-Riviere, M., Reiner, P., Mawet, J., Hervé, D., Buffon, F., Touzé, E., Domigo, V., Lamy, C., Calvet, D., Pasquini, M., Alamowitch, S., Favrole, P., Muresan, I.-P., Crozier, S., Rosso, C., Pires, C., Leger, A., Deltour, S., Cordonnier, C., Henon, H., Rossi, C., Zuber, M., Bruandet, M., Tamazyan, R., Join-Lambert, C., Juettler, E., Krause, T., Maul, S., Endres, M., Jungehulsing, G.J., Hennerici, M., Griebe, M., Sauer, T., Knoll, K., Huber, R., Knauer, K., Knauer, C., Raubold, S., Schneider, H., Hentschel, H., Lautenschläger, C., Schimmel, E., Dzialowski, I., Foerch, C., Lorenz, M., Singer, O., Meyer dos Santos, I.M.R., Hartmann, A., Hamann, A., Schacht, A., Schrader, B., Teíchmann, A., Wartenberg, K.E., Mueller, T.J., Jander, S., Gliem, M., Boettcher, C., Rosenkranz, M., Beck, C., Otto, D., Thomalla, G., Cheng, B., Wong, K.S., Leung, T.W., Soo, Y.O.Y., Prabhakar, S., Kesavarapu, S.R., Gajjela, P.K., Chenna, R.R., Ummer, K., Basheer, M., Andipet, A., Jagarlapudi, M.K.M., Mohammed, A.U.R., Pawar, V.G., Eranki, S.S.K., Singh, Y., Akhtar, N., Borah, N.C., Ghose, M., Choudhury, N., Ichaporia, N.R., Shendge, J., Khese, S., Pamidimukkala, V., Inbamuthaiah, P., Nuthakki, S.R., Tagallamudi, N.M.R., Gutti, A.K., Khurana, D., Kesavarapu, P., Jogi, V., Garg, A., Samanta, D., Sarma, G.R.K., Nadig, R., Mathew, T., Anandan, M.A., Caterbi, E., Zini, A., Cavazzuti, M., Casoni, F., Pentore, R., Falzone, F., Mazzoli, T., Greco, L.M., Menichetti, C., Coppola, F., Cenciarelli, S., Gallinella, E., Mattioni, A., Condurso, R., Sicilia, I., Zampolini, M., Corea, F., Barbi, M., Proietti, C., Toni, D., Pieroni, A., Anzini, A., Falcou, A., Demichele, M., Klijn, C.J.M., Tveiten, A., Thortveit, E.T., Pettersen, S., Holand, N., Hitland, B., Johnsen, S.H., Eltoft, A., Wasay, M., Kamal, A., Iqrar, A., Ali, L., Begum, D., Gama, G., Fonseca, L., Moreira, G., Veloso, L.M., Pinheiro, D., Paredes, L., Rozeira, C., Gregorio, T., Segura Martin, T., Ayo, O., Garcia-Garcia, J., Feria Vilar, I., Gómez Fernández, I., Amaro, S., Urra, X., Obach, V., Cervera, A., Silva, Y., Serena, J., Castellanos, M., Terceno, M., Van Eendenburg, C., Weck, A., Findling, O., Lüdi, R., Warburton, E.A., Day, D., Butler, N., Bumanlag, E., Caine, S., Steele, A., Osborn, M., Dodd, E., Murphy, P., Esisi, B., Brown, E., Hayman, R., Baliga, V.K.V., Minphone, M., Kennedy, J., Reckless, I., Pope, G., Teal, R., Michael, K., Manawadu, D., Kalra, L., Lewis, R., Mistry, B., Cattermole, E., Hassan, A., Mandizvidza, L., Bamford, J., Brooks, H., Bedford, C., Whiting, R., Baines, P., Hussain, M., Harvey, M., Fotherby, K., McBride, S., Bourke, P., Morgan, D., Jennings-Preece, K., Price, C., Huntley, S., Riddell, V.E., Storey, G., Lakey, R.L., Subramanian, G., Jenkinson, D., Kwan, J., David, O., Tiwari, D., James, M., Keenan, S., Eastwood, H., Shaw, L., Kaye, P., Button, D., Madigan, B., Williamson, D., Dixit, A., Davis, J., Hossain, M.O., Ford, G.A., Parry-Jones, A., O'Loughlin, V., Jarapa, R., Naing, Z., Lovelock, C., O'Reilly, J., Khan, U., Bhalla, A., Rudd, A., Birns, J., Werring, D.J., Law, R., Perry, R., Jones, I., Erande, R., Roffe, C., Natarajan, I., Ahmad, N., Finney, K., Lucas, J., Mistri, A., Eveson, D., Marsh, R., Haunton, V., Fugate, J.E., Lepore, S.W., Zheng, Danni, Sato, Shoichiro, Arima, Hisatomi, Heeley, Emma, Delcourt, Candice, Cao, Yongjun, Chalmers, John, and Anderson, Craig S.

Published
2016
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9. Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice:: GLORIA-AF Registry

Author

Lip G. Y. H., Kotalczyk A., Teutsch C., Diener H. -C., Dubner S. J., Halperin J. L., Ma C. -S., Rothman K. J., Marler S., Gurusamy V. K., Huisman M. V., Abban D. W., Aziz E., Kalan M. B., Abdul N., Backes L. M., Bradman D., Abud A. M., Badings E., Brautigam D., Adams F., Bagni E., Breton N., Addala S., Baker S. H., Brouwers P. J. A. M., Adragao P., Bala R., Browne K., Ageno W., Baldi A., Cortada J. B., Aggarwal R., Bando S., Bruni A., Agosti S., Banerjee S., Brunschwig C., Agostoni P., Bank A., Buathier H., Aguilar F., Esquivias G. B., Buhl A., Linares J. A., Barr C., Bullinga J., Aguinaga L., Bartlett M., Cabrera J. W., Ahmed J., Basic Kes V., Caccavo A., Aiello A., Baula G., Cai S., Ainsworth P., Behrens S., Caine S., Aiub J. R., Bell A., Calo L., Al-Dallow R., Benedetti R., Calvi V., Alderson L., Mazuecos J. B., Sanchez M. C., Velasco J. A. A., Benhalima B., Candeias R., Alexopoulos D., Bergler-Klein J., Capuano V., Manterola F. A., Berneau J. -B., Capucci A., Aliyar P., Bernstein R. A., Caputo R., Alonso D., Berrospi P., Rizo T. C., da Costa F. A. A., Berti S., Cardona F., Amado J., Berz A., da Costa Darrieux F. C., Amara W., Best E., Vera Y. C. D., Amelot M., Bettencourt P., Carolei A., Amjadi N., Betzu R., Carreno S., Ammirati F., Bhagwat R., Carvalho P., Andrade M., Bhatta L., Cary S., Andrawis N., Biscione F., Casu G., Annoni G., Bisignani G., Cavallini C., Ansalone G., Black T., Cayla G., Ariani M. K., Bloch M. J., Celentano A., Arias J. C., Bloom S., Cha T. -J., Armero S., Blumberg E., Cha K. S., Arora C., Bo M., Chae J. K., Aslam M. S., Bohmer E., Chalamidas K., Asselman M., Bollmann A., Challappa K., Audouin P., Bongiorni M. G., Chand S. P., Augenbraun C., Boriani G., Chandrashekar H., Aydin S., Boswijk D. J., Chartier L., Bott J., Chatterjee K., Ayryanova I., Bottacchi E., Ayala C. A. C., Cheema A., Davis G., Evonich R., Davy J. -M., Evseeva O., Chen L., Dayer M., Ezhov A., Chen S. -A., De Biasio M., Fahmy R., Chen J. H., De Bonis S., Fang Q., Chiang F. -T., De Caterina R., Farsad R., Chiarella F., De Franceschi T., Fauchier L., Chih-Chan L., de Groot J. R., Favale S., Cho Y. K., De Horta J., Fayard M., Choi J. -I., De La Briolle A., Fedele J. L., Choi D. J., de la Pena Topete G., Fedele F., Chouinard G., de Paola A. A. V., Fedorishina O., Chow D. H. -F., de Souza W., Fera S. R., Chrysos D., de Veer A., Ferreira L. G. G., Chumakova G., De Wolf L., Ferreira J., Valenzuela E. J. J. R. C., Decoulx E., Ferri C., Nica N. C., Deepak S., Ferrier A., Cislowski D. J., Defaye P., Ferro H., Clay A., Munoz F. D. -C., Finsen A., Clifford P., Brkljacic D. D., First B., Cohen A., Deumite N. J., Fischer S., Cohen M., Di Legge S., Fonseca C., Cohen S., Diemberger I., Almeida L. F., Colivicchi F., Dietz D., Forman S., Collins R., Dionisio P., Frandsen B., Colonna P., Dong Q., French W., Compton S., dos Santos F. R., Friedman K., Connolly D., Dotcheva E., Friese A., Conti A., Doukky R., Fruntelata A. G., Buenostro G. C., D'Souza A., Fujii S., Coodley G., Dubrey S., Fumagalli S., Cooper M., Ducrocq X., Fundamenski M., Coronel J., Dupljakov D., Furukawa Y., Corso G., Duque M., Gabelmann M., Sales J. C., Dutta D., Gabra N., Cottin Y., Duvilla N., Gadsboll N., Covalesky J., Duygun A., Galinier M., Cracan A., Dziewas R., Gammelgaard A., Crea F., Eaton C. B., Ganeshkumar P., Crean P., Eaves W., Gans C., Crenshaw J., Ebels-Tuinbeek L. A., Quintana A. G., Cullen T., Ehrlich C., Gartenlaub O., Darius H., Eichinger-Hasenauer S., Gaspardone A., Dary P., Eisenberg S. J., Genz C., Dascotte O., Jabali A. E., Georger F., Dauber I., Shahawy M. E., Georges J. -L., Davalos V., Hernandes M. E., Georgeson S., Davies R., Izal A. E., Giedrimas E., Gierba M., Haruna T., Jarmukli N., Ortega I. G., Hayek E., Jeanfreau R. J., Gillespie E., Healey J., Jenkins R. D., Giniger A., Hearne S., Sanchez C. J., Giudici M. C., Heffernan M., Jimenez J., Gkotsis A., Heggelund G., Jobe R., Glotzer T. V., Heijmeriks J. A., Joen-Jakobsen T., Gmehling J., Hemels M., Jones N., Gniot J., Hendriks I., Jorge J. C. M., Goethals P., Henein S., Jouve B., Goldbarg S., Her S. -H., Jung B. C., Goldberg R., Hermany P., Jung K. T., Goldmann B., Del Rio J. E. H., Jung W., Golitsyn S., Higashino Y., Kachkovskiy M., Gomez S., Hill M., Kafkala K., Mesa J. G., Hisadome T., Kalinina L., Gonzalez V. B., Hishida E., Kallmunzer B., Hermosillo J. A. G., Hoffer E., Kamali F., Lopez V. M. G., Hoghton M., Kamo T., Gorka H., Hong K., Kampus P., Gornick C., Hong S., Kashou H., Gorog D., Horbach S., Kastrup A., Gottipaty V., Horiuchi M., Katsivas A., Goube P., Hou Y., Kaufman E., Goudevenos I., Hsing J., Kawai K., Graham B., Huang C. -H., Kawajiri K., Greer G. S., Huckins D., Kazmierski J. F., Gremmler U., Hughes K., Keeling P., Grena P. G., Huizinga A., Saraiva J. F. K., Grond M., Hulsman E. L., Ketova G., Gronda E., Hung K. -C., Khaira A. S., Gronefeld G., Hwang G. -S., Khripun A., Gu X., Ikpoh M., Kim D. -I., Torres I. G. T., Imberti D., Kim Y. H., Guardigli G., Ince H., Kim N. H., Guevara C., Indolfi C., Kim D. K., Guignier A., Inoue S., Kim J. S., Gulizia M., Irles D., Gumbley M., Iseki H., Kim K. S., Gunther A., Israel C. N., Kim J., Ha A., Iteld B., Kinova E., Hahalis G., Iyer V., Klein A., Hakas J., Jackson-Voyzey E., Kmetzo J. J., Hall C., Jaffrani N., Kneller G. L., Han B., Jager F., Knezevic A., Han S., James M., Koh S. M. A., Hargrove J., Jang S. -W., Koide S., Hargroves D., Jaramillo N., Kollias A., Kooistra J. A., Li W., McClure J., Koons J., Li X., McCormack T., Koschutnik M., Lichy C., McGarity W., Kostis W. J., Lieber I., McIntyre H., Kovacic D., Rodriguez R. H. L., McLaurin B., Kowalczyk J., Lin H., Alvaro F., Palomino M., Koziolova N., Melandri F., Kraft P., Liu F., Meno H., Kragten J. A., Liu H., Menzies D., Krantz M., Esperon G. L., Mercader M., Krause L., Navarro N. L., Meyer C., Krenning B. J., Lo E., Meyer B. J., Krikke F., Lokshyn S., Miarka J., Kromhout Z., Lopez A., Mibach F., Krysiak W., Lopez-Sendon J. L., Michalski D., Kumar P., Filho A. M. L., Michel P., Kumler T., Lorraine R. S., Chreih R. M., Kuniss M., Luengas C. A., Luengas A., Mikdadi G., Kuo J. -Y., Luke R., Mikus M., Kuppers A., Luo M., Milicic D., Kurrelmeyer K., Lupovitch S., Militaru C., Kwak C. H., Lyrer P., Minaie S., Laboulle B., Ma C., Minescu B., Labovitz A., Ma G., Mintale I., Ter Lai W., Madariaga I., Mirault T., Lam A., Maeno K., Mirro M. J., Lam Y. Y., Magnin D., Mistry D., Lanas Zanetti F., Maid G., Miu N. V., Landau C., Mainigi S. K., Miyamoto N., Landini G., Makaritsis K., Moccetti T., Lanna Figueiredo E., Malhotra R., Mohammed A., Larsen T., Manning R., Nor A. M., Lavandier K., Manolis A., Mollerus M., LeBlanc J., Hurtado H. A. M., Molon G., Lee M. H., Mantas I., Mondillo S., Lee C. -H., Jattin F. M., Moniz P., Lehman J., Maqueda V., Mont L., Leitao A., Marchionni N., Montagud V., Lellouche N., Ortuno F. M., Montana O., Lelonek M., Santana A. M., Monti C., Lenarczyk R., Martinez J., Moretti L., Lenderink T., Maskova P., Mori K., Gonzalez S. L., Hernandez N. M., Moriarty A., Leong-Sit P., Matsuda K., Morka J., Leschke M., Maurer T., Moschini L., Ley N., Mauro C., Moschos N., Li Z., May E., Mugge A., Mayer N., Mulhearn T. J., Muresan C., Jose E. P., Precoma D. B., Muriago M., Padilla F. G. P., Prelle A., Musial W., Rios V. P., Prodafikas J., Musser C. W., Pajes G., Protasov K., Musumeci F., Pandey A. S., Pye M., Nageh T., Paparella G., Qiu Z., Nakagawa H., Paris F., Quedillac J. -M., Nakamura Y., Park H. W., Raev D., Nakayama T., Park J. S., Grado C. A. R., Nam G. -B., Parthenakis F., Rahimi S., Nanna M., Passamonti E., Raisaro A., Natarajan I., Patel R. J., Rama B., Nayak H. M., Patel J., Ramos R., Naydenov S., Patel M., Ranieri M., Nazlic J., Patrick J., Raposo N., Nechita A. C., Jimenez R. P., Rashba E., Nechvatal L., Paz A., Rauch-Kroehnert U., Negron S. A., Pengo V., Reddy R., Neiman J., Pentz W., Renda G., Neuenschwander F. C., Perez B., Reza S., Neves D., Rios A. M. P., Ria L., Neykova A., Perez-Cabezas A., Richter D., Miguel R. N., Perlman R., Rickli H., Nijmeh G., Persic V., Rieker W., Nizov A., Perticone F., Vera T. R., Campos R. N., Peters T. K., Ritt L. E., Nossan J., Petkar S., Roberts D., Novikova T., Pezo L. F., Briones I. 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Chreih R.M., Kuniss M., Luengas C.A., Luengas A., Mikdadi G., Kuo J.-Y., Luke R., Mikus M., Kuppers A., Luo M., Milicic D., Kurrelmeyer K., Lupovitch S., Militaru C., Kwak C.H., Lyrer P., Minaie S., Laboulle B., Ma C., Minescu B., Labovitz A., Ma G., Mintale I., Ter Lai W., Madariaga I., Mirault T., Lam A., Maeno K., Mirro M.J., Lam Y.Y., Magnin D., Mistry D., Lanas Zanetti F., Maid G., Miu N.V., Landau C., Mainigi S.K., Miyamoto N., Landini G., Makaritsis K., Moccetti T., Lanna Figueiredo E., Malhotra R., Mohammed A., Larsen T., Manning R., Nor A.M., Lavandier K., Manolis A., Mollerus M., LeBlanc J., Hurtado H.A.M., Molon G., Lee M.H., Mantas I., Mondillo S., Lee C.-H., Jattin F.M., Moniz P., Lehman J., Maqueda V., Mont L., Leitao A., Marchionni N., Montagud V., Lellouche N., Ortuno F.M., Montana O., Lelonek M., Santana A.M., Monti C., Lenarczyk R., Martinez J., Moretti L., Lenderink T., Maskova P., Mori K., Gonzalez S.L., Hernandez N.M., Moriarty A., Leong-Sit P., Matsuda K., Morka J., Leschke M., Maurer T., Moschini L., Ley N., Mauro C., Moschos N., Li Z., May E., Mugge A., Mayer N., Mulhearn T.J., Muresan C., Jose E.P., Precoma D.B., Muriago M., Padilla F.G.P., Prelle A., Musial W., Rios V.P., Prodafikas J., Musser C.W., Pajes G., Protasov K., Musumeci F., Pandey A.S., Pye M., Nageh T., Paparella G., Qiu Z., Nakagawa H., Paris F., Quedillac J.-M., Nakamura Y., Park H.W., Raev D., Nakayama T., Park J.S., Grado C.A.R., Nam G.-B., Parthenakis F., Rahimi S., Nanna M., Passamonti E., Raisaro A., Natarajan I., Patel R.J., Rama B., Nayak H.M., Patel J., Ramos R., Naydenov S., Patel M., Ranieri M., Nazlic J., Patrick J., Raposo N., Nechita A.C., Jimenez R.P., Rashba E., Nechvatal L., Paz A., Rauch-Kroehnert U., Negron S.A., Pengo V., Reddy R., Neiman J., Pentz W., Renda G., Neuenschwander F.C., Perez B., Reza S., Neves D., Rios A.M.P., Ria L., Neykova A., Perez-Cabezas A., Richter D., Miguel R.N., Perlman R., Rickli H., Nijmeh G., Persic V., Rieker W., Nizov A., 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M., Sasaoka T., de Souza O.F., Turk S., Sati H., Sparby J.A., Turner W., Savelieva I., Spinar J., Tveit A., Scala P.-J., Sprigings D., Tytus R., Schellinger P., Spyropoulos A.C., Valadao C., Scherr C., Stakos D., van Bergen P.F.M.M., Schmitz L., Steinwender C., van de Borne P., Schmitz K.-H., Stergiou G., van den Berg B.J., Schmitz B., Stiell I., van der Zwaan C., Schnabel T., Stoddard M., Van Eck M., Schnupp S., Stoikov A., Vanacker P., Schoeniger P., Streb W., Vasilev D., Schon N., Styliadis I., Vasilikos V., Schwimmbeck P., Su G., Vasilyev M., Seamark C., Su X., Veerareddy S., Searles G., Sudnik W., Mino M.V., Seidl K.-H., Sukles K., Venkataraman A., Seidman B., Sun X., Verdecchia P., Sek J., Swart H., Versaci F., Sekaran L., Szavits-Nossan J., Vester E.G., Serrati C., Taggeselle J., Vial H., Shah N., Takagi Y., Victory J., Shah V., Takhar A.P.S., Villamil A., Shah A., Tamm A., Vincent M., Shah S., Tanaka K., Vlastaris A., Sharma V.K., Tanawuttiwat T., Dahl J., Shaw L., Tang S., 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Zhang D., Zukerman L.S., Yamanoue H., Zhang X., and Yamashita T.

Subjects
Apixaban, Atrial fibrillation, Dabigatran, Non-vitamin K antagonists, Rivaroxaban, Pyridones, Medizin, Myocardial Infarction, Administration, Oral, Anticoagulants, Hemorrhage, General Medicine, Non-vitamin K antagonist, Stroke, Clinical Trials, Phase III as Topic, Humans, Prospective Studies, Registries, Cardiology and Cardiovascular Medicine
Abstract

Background and purpose Prospectively collected data comparing the safety and effectiveness of individual non-vitamin K antagonists (NOACs) are lacking. Our objective was to directly compare the effectiveness and safety of NOACs in patients with newly diagnosed atrial fibrillation (AF). Methods In GLORIA-AF, a large, prospective, global registry program, consecutive patients with newly diagnosed AF were followed for 3 years. The comparative analyses for (1) dabigatran vs rivaroxaban or apixaban and (2) rivaroxaban vs apixaban were performed on propensity score (PS)-matched patient sets. Proportional hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest. Results The GLORIA-AF Phase III registry enrolled 21,300 patients between January 2014 and December 2016. Of these, 3839 were prescribed dabigatran, 4015 rivaroxaban and 4505 apixaban, with median ages of 71.0, 71.0, and 73.0 years, respectively. In the PS-matched set, the adjusted HRs and 95% confidence intervals (CIs) for dabigatran vs rivaroxaban were, for stroke: 1.27 (0.79–2.03), major bleeding 0.59 (0.40–0.88), myocardial infarction 0.68 (0.40–1.16), and all-cause death 0.86 (0.67–1.10). For the comparison of dabigatran vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 1.16 (0.76–1.78), myocardial infarction 0.84 (0.48–1.46), major bleeding 0.98 (0.63–1.52) and all-cause death 1.01 (0.79–1.29). For the comparison of rivaroxaban vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 0.78 (0.52–1.19), myocardial infarction 0.96 (0.63–1.45), major bleeding 1.54 (1.14–2.08), and all-cause death 0.97 (0.80–1.19). Conclusions Patients treated with dabigatran had a 41% lower risk of major bleeding compared with rivaroxaban, but similar risks of stroke, MI, and death. Relative to apixaban, patients treated with dabigatran had similar risks of stroke, major bleeding, MI, and death. Rivaroxaban relative to apixaban had increased risk for major bleeding, but similar risks for stroke, MI, and death. Registration URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01468701, NCT01671007. Date of registration: September 2013. Graphical abstract

Published
2022
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12. CalDAG-GEFI mediates striatal cholinergic modulation of dendritic excitability, synaptic plasticity and psychomotor behaviors

Author

Crittenden, Jill R., primary, Zhai, Shenyu, additional, Sauvage, Magdalena, additional, Kitsukawa, Takashi, additional, Burguière, Eric, additional, Thomsen, Morgane, additional, Zhang, Hui, additional, Costa, Cinzia, additional, Martella, Giuseppina, additional, Ghiglieri, Veronica, additional, Picconi, Barbara, additional, Pescatore, Karen A., additional, Unterwald, Ellen M., additional, Jackson, Walker S., additional, Housman, David E., additional, Caine, S. Barak, additional, Sulzer, David, additional, Calabresi, Paolo, additional, Smith, Anne C., additional, Surmeier, D. James, additional, and Graybiel, Ann M., additional

Published
2021
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14. Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.

Author

Best J.G., Ambler G., Wilson D., Lee K.-J., Lim J.-S., Shiozawa M., Koga M., Li L., Lovelock C., Chabriat H., Hennerici M., Wong Y.K., Mak H.K.F., Prats-Sanchez L., Martinez-Domeno A., Inamura S., Yoshifuji K., Arsava E.M., Horstmann S., Purrucker J., Lam B.Y.K., Wong A., Kim Y.D., Song T.-J., Lemmens R., Eppinger S., Gattringer T., Uysal E., Tanriverdi Z., Bornstein N.M., Ben Assayag E., Hallevi H., Molad J., Nishihara M., Tanaka J., Coutts S.B., Polymeris A., Wagner B., Seiffge D.J., Lyrer P., Algra A., Kappelle L.J., Al-Shahi Salman R., Jager H.R., Lip G.Y.H., Fischer U., El-Koussy M., Mas J.-L., Legrand L., Karayiannis C., Phan T., Gunkel S., Christ N., Abrigo J., Leung T., Chu W., Chappell F., Makin S., Hayden D., Williams D.J., Mess W.H., Nederkoorn P.J., Barbato C., Browning S., Wiegertjes K., Tuladhar A.M., Maaijwee N., Guevarra A.C., Yatawara C., Mendyk A.-M., Delmaire C., Kohler S., van Oostenbrugge R., Zhou Y., Xu C., Hilal S., Gyanwali B., Chen C., Lou M., Staals J., Bordet R., Kandiah N., de Leeuw F.-E., Simister R., Hendrikse J., Kelly P.J., Wardlaw J., Soo Y., Fluri F., Srikanth V., Calvet D., Jung S., Kwa V.I.H., Engelter S.T., Peters N., Smith E.E., Hara H., Yakushiji Y., Orken D.N., Fazekas F., Thijs V., Heo J.H., Mok V., Veltkamp R., Ay H., Imaizumi T., Gomez-Anson B., Lau K.K., Jouvent E., Rothwell P.M., Toyoda K., Bae H.-J., Marti-Fabregas J., Werring D.J., Harkness K., Shaw L., Sword J., Mohd Nor A., Sharma P., Kelly D., Harrington F., Randall M., Smith M., Mahawish K., Elmarim A., Esisi B., Cullen C., Nallasivam A., Price C., Barry A., Roffe C., Coyle J., Hassan A., Birns J., Cohen D., Sekaran L., Parry-Jones A., Parry A., Hargroves D., Proschel H., Datta P., Darawil K., Manoj A., Burn M., Patterson C., Giallombardo E., Smyth N., Mansoor S., Anwar I., Marsh R., Ispoglou S., Chadha D., Prabhakaran M., Meenakishundaram S., O'Connell J., Scott J., Krishnamurthy V., Aghoram P., McCormick M., Sprigg N., O'Mahony P., Cooper M., Choy L., Wilkinson P., Leach S., Caine S., Burger I., Gunathilagan G., Guyler P., Emsley H., Davis M., Manawadu D., Pasco K., Mamun M., Luder R., Sajid M., Okwera J., Warburton E., Saastamoinen K., England T., Putterill J., Flossman E., Power M., Dani K., Mangion D., Suman A., Corrigan J., Lawrence E., Vahidassr D., Shakeshaft C., Brown M., Charidimou A., Cohen H., Banerjee G., Houlden H., White M., Yousry T., Flossmann E., Muir K., Gratz P., Mattle H., Panos L., Korczyn A., Kliper E., Maeder P., Gass A., Pachai C., Bracoub L., Douste-Blazy M.-Y., Fratacci M.D., Vicaut E., Sato S., Miwa K., Fujita K., Ide T., Ma H., Ly J., Singhal S., Chandra R., Slater L.-A., Soufan C., Moran C., Traenka C., Thilemann S., Fladt J., Gensicke H., Bonati L., Kim B.J., Han M.-K., Kang J., Ko E., Yang M.H., Jang M.S., Murphy S., Carty F., Akijian L., Thornton J., Schembri M., Douven E., Delgado-Mederos R., Marin R., Camps-Renom P., Guisado-Alonso D., Nunez F., Medrano-Martorell S., Merino E., Iida K., Ikeda S., Irie H., Demirelli D.S., Medanta J.M., Zerna C., Hernandez M.V., Armitage P., Heye A., Munoz-Maniega S., Sakka E., Thrippleton M., Dennis M., Beigneux Y., Silva M., Venketasubramanian N., Ho S.L., Cheung R.T.F., Chan K.H., Teo K.C., Hui E., Kwan J.S.K., Chang R., Tse M.Y., Hoi C.P., Chan C.Y., Chan O.L., Cheung R.H.K., Wong E.K.M., Leung K.T., Tsang S.F., Ip H.L., Ma S.H., Ma K., Fong W.C., Li S.H., Li R., Ng P.W., Wong K.K., Liu W., Wong L., Ramos L., De Schryver E., Jobsis J., van der Sande J., Brouwers P., Roos Y., Stam J., Bakker S., Verbiest H., Schoonewille W., Linn C., Hertzberger L., van Gemert M., Berntsen P., Van Dam-Nolen D., Kooi M.E., Van der Lugt A., Koudstaal P., Leff A., Ward N., Nachev P., Perry R., Ozkan H., Mitchell J., Best J.G., Ambler G., Wilson D., Lee K.-J., Lim J.-S., Shiozawa M., Koga M., Li L., Lovelock C., Chabriat H., Hennerici M., Wong Y.K., Mak H.K.F., Prats-Sanchez L., Martinez-Domeno A., Inamura S., Yoshifuji K., Arsava E.M., Horstmann S., Purrucker J., Lam B.Y.K., Wong A., Kim Y.D., Song T.-J., Lemmens R., Eppinger S., Gattringer T., Uysal E., Tanriverdi Z., Bornstein N.M., Ben Assayag E., Hallevi H., Molad J., Nishihara M., Tanaka J., Coutts S.B., Polymeris A., Wagner B., Seiffge D.J., Lyrer P., Algra A., Kappelle L.J., Al-Shahi Salman R., Jager H.R., Lip G.Y.H., Fischer U., El-Koussy M., Mas J.-L., Legrand L., Karayiannis C., Phan T., Gunkel S., Christ N., Abrigo J., Leung T., Chu W., Chappell F., Makin S., Hayden D., Williams D.J., Mess W.H., Nederkoorn P.J., Barbato C., Browning S., Wiegertjes K., Tuladhar A.M., Maaijwee N., Guevarra A.C., Yatawara C., Mendyk A.-M., Delmaire C., Kohler S., van Oostenbrugge R., Zhou Y., Xu C., Hilal S., Gyanwali B., Chen C., Lou M., Staals J., Bordet R., Kandiah N., de Leeuw F.-E., Simister R., Hendrikse J., Kelly P.J., Wardlaw J., Soo Y., Fluri F., Srikanth V., Calvet D., Jung S., Kwa V.I.H., Engelter S.T., Peters N., Smith E.E., Hara H., Yakushiji Y., Orken D.N., Fazekas F., Thijs V., Heo J.H., Mok V., Veltkamp R., Ay H., Imaizumi T., Gomez-Anson B., Lau K.K., Jouvent E., Rothwell P.M., Toyoda K., Bae H.-J., Marti-Fabregas J., Werring D.J., Harkness K., Shaw L., Sword J., Mohd Nor A., Sharma P., Kelly D., Harrington F., Randall M., Smith M., Mahawish K., Elmarim A., Esisi B., Cullen C., Nallasivam A., Price C., Barry A., Roffe C., Coyle J., Hassan A., Birns J., Cohen D., Sekaran L., Parry-Jones A., Parry A., Hargroves D., Proschel H., Datta P., Darawil K., Manoj A., Burn M., Patterson C., Giallombardo E., Smyth N., Mansoor S., Anwar I., Marsh R., Ispoglou S., Chadha D., Prabhakaran M., Meenakishundaram S., O'Connell J., Scott J., Krishnamurthy V., Aghoram P., McCormick M., Sprigg N., O'Mahony P., Cooper M., Choy L., Wilkinson P., Leach S., Caine S., Burger I., Gunathilagan G., Guyler P., Emsley H., Davis M., Manawadu D., Pasco K., Mamun M., Luder R., Sajid M., Okwera J., Warburton E., Saastamoinen K., England T., Putterill J., Flossman E., Power M., Dani K., Mangion D., Suman A., Corrigan J., Lawrence E., Vahidassr D., Shakeshaft C., Brown M., Charidimou A., Cohen H., Banerjee G., Houlden H., White M., Yousry T., Flossmann E., Muir K., Gratz P., Mattle H., Panos L., Korczyn A., Kliper E., Maeder P., Gass A., Pachai C., Bracoub L., Douste-Blazy M.-Y., Fratacci M.D., Vicaut E., Sato S., Miwa K., Fujita K., Ide T., Ma H., Ly J., Singhal S., Chandra R., Slater L.-A., Soufan C., Moran C., Traenka C., Thilemann S., Fladt J., Gensicke H., Bonati L., Kim B.J., Han M.-K., Kang J., Ko E., Yang M.H., Jang M.S., Murphy S., Carty F., Akijian L., Thornton J., Schembri M., Douven E., Delgado-Mederos R., Marin R., Camps-Renom P., Guisado-Alonso D., Nunez F., Medrano-Martorell S., Merino E., Iida K., Ikeda S., Irie H., Demirelli D.S., Medanta J.M., Zerna C., Hernandez M.V., Armitage P., Heye A., Munoz-Maniega S., Sakka E., Thrippleton M., Dennis M., Beigneux Y., Silva M., Venketasubramanian N., Ho S.L., Cheung R.T.F., Chan K.H., Teo K.C., Hui E., Kwan J.S.K., Chang R., Tse M.Y., Hoi C.P., Chan C.Y., Chan O.L., Cheung R.H.K., Wong E.K.M., Leung K.T., Tsang S.F., Ip H.L., Ma S.H., Ma K., Fong W.C., Li S.H., Li R., Ng P.W., Wong K.K., Liu W., Wong L., Ramos L., De Schryver E., Jobsis J., van der Sande J., Brouwers P., Roos Y., Stam J., Bakker S., Verbiest H., Schoonewille W., Linn C., Hertzberger L., van Gemert M., Berntsen P., Van Dam-Nolen D., Kooi M.E., Van der Lugt A., Koudstaal P., Leff A., Ward N., Nachev P., Perry R., Ozkan H., and Mitchell J.

Abstract

Background: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. Method(s): We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. Finding(s): The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0.73 (95% CI 0.69-0.77) with a calibration slope of 0.94 (0.81-1.06) for the intracranial haemorrhage model and 0.63 (0.62-0.65) w

Published
2021

15. CalDAG-GEFI mediates striatal cholinergic modulation of dendritic excitability, synaptic plasticity and psychomotor behaviors

Author

Crittenden, Jill R., Zhai, Shenyu, Sauvage, Magdalena, Kitsukawa, Takashi, Burguiere, Eric, Thomsen, Morgane, Zhang, Hui, Costa, Cinzia, Martella, Giuseppina, Ghiglieri, Veronica, Picconi, Barbara, Pescatore, Karen A., Unterwald, Ellen M., Jackson, Walker, Housman, David E., Caine, S. Barak, Sulzer, David, Calabresi, Paolo, Smith, Anne C., Surmeier, D. James, Graybiel, Ann M., Crittenden, Jill R., Zhai, Shenyu, Sauvage, Magdalena, Kitsukawa, Takashi, Burguiere, Eric, Thomsen, Morgane, Zhang, Hui, Costa, Cinzia, Martella, Giuseppina, Ghiglieri, Veronica, Picconi, Barbara, Pescatore, Karen A., Unterwald, Ellen M., Jackson, Walker, Housman, David E., Caine, S. Barak, Sulzer, David, Calabresi, Paolo, Smith, Anne C., Surmeier, D. James, and Graybiel, Ann M.

Abstract

CalDAG-GEFI (CDGI) is a protein highly enriched in the striatum, particularly in the principal spiny projection neurons (SPNs). CDGI is strongly down-regulated in two hyperkinetic conditions related to striatal dysfunction: Huntingtons disease and levodopa-induced dyskinesia in Parkinsons disease. We demonstrate that genetic deletion of CDGI in mice disrupts dendritic, but not somatic, M1 muscarinic receptors (M1Rs) signaling in indirect pathway SPNs. Loss of CDGI reduced temporal integration of excitatory postsynaptic potentials at dendritic glutamatergic synapses and impaired the induction of activity-dependent long-term potentiation. CDGI deletion selectively increased psychostimulant-induced repetitive behaviors, disrupted sequence learning, and eliminated M1R blockade of cocaine self-administration. These findings place CDGI as a major, but previously unrecognized, mediator of cholinergic signaling in the striatum. The effects of CDGI deletion on the selfadministration of drugs of abuse and its marked alterations in hyperkinetic extrapyramidal disorders highlight CDGIs therapeutic potential., Funding Agencies: William N. & Bernice E. Bumpus Foundation; Saks Kavanaugh Foundation; Simons Foundation; National Institute of Child Health and Development United States Department of Health & Human Services National Institutes of Health (NIH) - USANIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [R37 HD028341]; James and Pat Poitras Research Fund; Stanley Center for Psychiatric Research at the Broad Institute; National Institute of Mental Health United States Department of Health & Human Services National Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01 MH071847, F32 MH065815]; National Institute on Aging United States Department of Health & Human Services National Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [R01 AG050548]; European Community FP7 - The-matic priority HEALTH contract [222918]; Ministry of Health; JPB Foundation; National Institute on Drug Abuse United States Department of Health & Human Services National Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA) European Commission [R00 DA027825, R01 DA07418]

Published
2021
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16. CalDAG-GEFI mediates striatal cholinergic modulation of dendritic excitability, synaptic plasticity and psychomotor behaviors

Author

McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Koch Institute for Integrative Cancer Research at MIT, Crittenden, Jill R, Zhai, Shenyu, Sauvage, Magdalena, Kitsukawa, Takashi, Burguière, Eric, Thomsen, Morgane, Zhang, Hui, Costa, Cinzia, Martella, Giuseppina, Ghiglieri, Veronica, Picconi, Barbara, Pescatore, Karen A, Unterwald, Ellen M, Jackson, Walker S, Housman, David E, Caine, S Barak, Sulzer, David, Calabresi, Paolo, Smith, Anne C, Surmeier, D James, Graybiel, Ann M, McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Koch Institute for Integrative Cancer Research at MIT, Crittenden, Jill R, Zhai, Shenyu, Sauvage, Magdalena, Kitsukawa, Takashi, Burguière, Eric, Thomsen, Morgane, Zhang, Hui, Costa, Cinzia, Martella, Giuseppina, Ghiglieri, Veronica, Picconi, Barbara, Pescatore, Karen A, Unterwald, Ellen M, Jackson, Walker S, Housman, David E, Caine, S Barak, Sulzer, David, Calabresi, Paolo, Smith, Anne C, Surmeier, D James, and Graybiel, Ann M

Abstract

CalDAG-GEFI (CDGI) is a protein highly enriched in the striatum, particularly in the principal spiny projection neurons (SPNs). CDGI is strongly down-regulated in two hyperkinetic conditions related to striatal dysfunction: Huntington's disease and levodopa-induced dyskinesia in Parkinson's disease. We demonstrate that genetic deletion of CDGI in mice disrupts dendritic, but not somatic, M1 muscarinic receptors (M1Rs) signaling in indirect pathway SPNs. Loss of CDGI reduced temporal integration of excitatory postsynaptic potentials at dendritic glutamatergic synapses and impaired the induction of activity-dependent long-term potentiation. CDGI deletion selectively increased psychostimulant-induced repetitive behaviors, disrupted sequence learning, and eliminated M1R blockade of cocaine self-administration. These findings place CDGI as a major, but previously unrecognized, mediator of cholinergic signaling in the striatum. The effects of CDGI deletion on the self-administration of drugs of abuse and its marked alterations in hyperkinetic extrapyramidal disorders highlight CDGI's therapeutic potential.

Published
2021

17. Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation: The GLORIA-AF registry

Author

Ntaios, G., Huisman, M. V., Diener, H. -C., Halperin, J. L., Teutsch, C., Marler, S., Gurusamy, V. K., Thompson, M., Lip, G. Y. H., Olshansky, B., Abban, D. W., Abdul, N., Abud, A. M., Adams, F., Addala, S., Adragao, P., Ageno, W., Aggarwal, R., Agosti, S., Agostoni, P., Aguilar, F., Linares, J. A., Aguinaga, L., Ahmed, J., Aiello, A., Ainsworth, P., Aiub, J. R., Al-Dallow, R., Alderson, L., Aldrete Velasco, J. A., Alexopoulos, D., Manterola, F. A., Aliyar, P., Alonso, D., Alves da Costa, F. A., Amado, J., Amara, W., Amelot, M., Amjadi, N., Ammirati, F., Andrade, M., Andrawis, N., Annoni, G., Ansalone, G., Ariani, M. K., Arias, J. C., Armero, S., Arora, C., Aslam, M. S., Asselman, M., Audouin, P., Augenbraun, C., Aydin, S., Ayryanova, I., Aziz, E., Backes, L. M., Badings, E., Bagni, E., Baker, S. H., Bala, R., Baldi, A., Bando, S., Banerjee, S., Bank, A., Esquivias, G. B., Barr, C., Bartlett, M., Kes, V. B., Baula, G., Behrens, S., Bell, A., Benedetti, R., Mazuecos, J. B., Benhalima, B., Bergler-Klein, J., Berneau, J. -B., Bernstein, R. A., Berrospi, P., Berti, S., Berz, A., Best, E., Bettencourt, P., Betzu, R., Bhagwat, R., Bhatta, L., Biscione, F., Bisignani, G., Black, T., Bloch, M. J., Bloom, S., Blumberg, E., Bo, M., Bohmer, E., Bollmann, A., Bongiorni, M. G., Boriani, G., Boswijk, D. J., Bott, J., Bottacchi, E., Kalan, M. B., Bradman, D., Brautigam, D., Breton, N., Brouwers, P. J. A. M., Browne, K., Cortada, J. B., Bruni, A., Brunschwig, C., Buathier, H., Buhl, A., Bullinga, J., Cabrera, J. W., Caccavo, A., Cai, S., Caine, S., Calo, L., Calvi, V., Sanchez, M. C., Candeias, R., Capuano, V., Capucci, A., Caputo, R., Rizo, T. C., Cardona, F., Carlos da Costa Darrieux, F., Duarte Vera, Y. C., Carolei, A., Carreno, S., Carvalho, P., Cary, S., Casu, G., Cavallini, C., Cayla, G., Celentano, A., Cha, T. -J., Cha, K. S., Chae, J. K., Chalamidas, K., Challappa, K., Chand, S. P., Chandrashekar, H., Chartier, L., Chatterjee, K., Chavez Ayala, C. A., Cheema, A., Chen, L., Chen, S. -A., Chen, J. H., Chiang, F. -T., Chiarella, F., Chih-Chan, L., Cho, Y. K., Choi, J. -I., Choi, D. J., Chouinard, G., Hoi-Fan Chow, D., Chrysos, D., Chumakova, G., Jose Roberto Chuquiure Valenzuela, E. J., Nica, N. C., Cislowski, D. J., Clay, A., Clifford, P., Cohen, A., Cohen, M., Cohen, S., Colivicchi, F., Collins, R., Colonna, P., Compton, S., Connolly, D., Conti, A., Buenostro, G. C., Coodley, G., Cooper, M., Coronel, J., Corso, G., Sales, J. C., Cottin, Y., Covalesky, J., Cracan, A., Crea, Filippo, Crean, P., Crenshaw, J., Cullen, T., Darius, H., Dary, P., Dascotte, O., Dauber, I., Davalos, V., Davies, R., Davis, G., Davy, J. -M., Dayer, M., De Biasio, M., De Bonis, S., De Caterina, R., De Franceschi, T., de Groot, J. R., De Horta, J., De La Briolle, A., Topete, G. D. L. P., Vicenzo de Paola, A. A., de Souza, W., de Veer, A., De Wolf, L., Decoulx, E., Deepak, S., Defaye, P., Del-Carpio Munoz, F., Brkljacic, D. D., Deumite, N. J., Di Legge, S., Diemberger, I., Dietz, D., Dionisio, P., Dong, Q., Rossi dos Santos, F., Dotcheva, E., Doukky, R., D'Souza, A., Dubrey, S., Ducrocq, X., Dupljakov, D., Duque, M., Dutta, D., Duvilla, N., Duygun, A., Dziewas, R., Eaton, C. B., Eaves, W., Ebels-Tuinbeek, L. A., Ehrlich, C., Eichinger-Hasenauer, S., Eisenberg, S. J., El Jabali, A., El Shahawy, M., Hernandes, M. E., Izal, A. E., Evonich, R., Evseeva, O., Ezhov, A., Fahmy, R., Fang, Q., Farsad, R., Fauchier, L., Favale, S., Fayard, M., Fedele, J. L., Fedele, F., Fedorishina, O., Fera, S. R., Gomes Ferreira, L. G., Ferreira, J., Ferri, C., Ferrier, A., Ferro, H., Finsen, A., First, B., Fischer, S., Fonseca, C., Almeida, L. F., Forman, S., Frandsen, B., French, W., Friedman, K., Friese, A., Fruntelata, A. G., Fujii, S., Fumagalli, S., Fundamenski, M., Furukawa, Y., Gabelmann, M., Gabra, N., Gadsboll, N., Galinier, M., Gammelgaard, A., Ganeshkumar, P., Gans, C., Quintana, A. G., Gartenlaub, O., Gaspardone, A., Genz, C., Georger, F., Georges, J. -L., Georgeson, S., Giedrimas, E., Gierba, M., Ortega, I. G., Gillespie, E., Giniger, A., Giudici, M. C., Gkotsis, A., Glotzer, T. V., Gmehling, J., Gniot, J., Goethals, P., Goldbarg, S., Goldberg, R., Goldmann, B., Golitsyn, S., Gomez, S., Mesa, J. G., Gonzalez, V. B., Gonzalez Hermosillo, J. A., Gonzalez Lopez, V. M., Gorka, H., Gornick, C., Gorog, D., Gottipaty, V., Goube, P., Goudevenos, I., Graham, B., Greer, G. S., Gremmler, U., Grena, P. G., Grond, M., Gronda, E., Gronefeld, G., Gu, X., Torres Torres, I. G., Guardigli, G., Guevara, C., Guignier, A., Gulizia, M., Gumbley, M., Gunther, A., Ha, A., Hahalis, G., Hakas, J., Hall, C., Han, B., Han, S., Hargrove, J., Hargroves, D., Harris, K. B., Haruna, T., Hayek, E., Healey, J., Hearne, S., Heffernan, M., Heggelund, G., Heijmeriks, J. A., Hemels, M., Hendriks, I., Henein, S., Her, S. -H., Hermany, P., Hernandez Del Rio, J. E., Higashino, Y., Hill, M., Hisadome, T., Hishida, E., Hoffer, E., Hoghton, M., Hong, K., Hong, S. K., Horbach, S., Horiuchi, M., Hou, Y., Hsing, J., Huang, C. -H., Huckins, D., Kathy, Hughe, Huizinga, A., Hulsman, E. L., Hung, K. -C., Hwang, G. -S., Ikpoh, M., Imberti, D., Ince, H., Indolfi, C., Inoue, S., Irles, D., Iseki, H., Israel, C. N., Iteld, B., Iyer, V., Jackson-Voyzey, E., Jaffrani, N., Jager, F., James, M., Jang, S. -W., Jaramillo, N., Jarmukli, N., Jeanfreau, R. J., Jenkins, R. D., Sanchez, C. J., Jimenez, J., Jobe, R., Joen-Jakobsen, T., Jones, N., Moura Jorge, J. C., Jouve, B., Jung, B. C., Jung, K. T., Jung, W., Kachkovskiy, M., Kafkala, K., Kalinina, L., Kallmunzer, B., Kamali, F., Kamo, T., Kampus, P., Kashou, H., Kastrup, A., Katsivas, A., Kaufman, E., Kawai, K., Kawajiri, K., Kazmierski, J. F., Keeling, P., Kerr Saraiva, J. F., Ketova, G., Khaira, A. S., Khripun, A., Kim, D. -I., Kim, Y. H., Kim, N. H., Kim, D. K., Kim, J. S., Kim, K. S., Kim, J. B., Kinova, E., Klein, A., Kmetzo, J. J., Kneller, G. L., Knezevic, A., Angela Koh, S. M., Koide, S., Kollias, A., Kooistra, J. A., Koons, J., Koschutnik, M., Kostis, W. J., Kovacic, D., Kowalczyk, J., Koziolova, N., Kraft, P., Kragten, J. A., Krantz, M., Krause, L., Krenning, B. J., Krikke, F., Kromhout, Z., Krysiak, W., Kumar, P., Kumler, T., Kuniss, M., Kuo, J. -Y., Kuppers, A., Kurrelmeyer, K., Kwak, C. H., Laboulle, B., Labovitz, A., Lai, W. T., Lam, A., Lam, Y. Y., Zanetti, F. L., Landau, C., Landini, G., Figueiredo, E. L., Larsen, T., Lavandier, K., Leblanc, J., Lee, M. H., Lee, C. -H., Lehman, J., Leitao, A., Lellouche, N., Lelonek, M., Lenarczyk, R., Lenderink, T., Gonzalez, S. L., Leong-Sit, P., Leschke, M., Ley, N., Li, Z., Li, X., Li, W., Lichy, C., Lieber, I., Limon Rodriguez, R. H., Lin, H., Liu, F., Liu, H., Esperon, G. L., Navarro, N. L., Lo, E., Lokshyn, S., Lopez, A., Lopez-Sendon, J. L., Lorga Filho, A. M., Lorraine, R. S., Luengas, C. 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S., Paparella, G., Paris, F., Park, H. W., Park, J. S., Parthenakis, F., Passamonti, E., Patel, R. J., Patel, J., Patel, M., Patrick, J., Jimenez, R. P., Paz, A., Pengo, V., Pentz, W., Perez, B., Perez Rios, A. M., Perez-Cabezas, A., Perlman, R., Persic, V., Perticone, F., Peters, T. K., Petkar, S., Pezo, L. F., Pflucke, C., Pham, D. N., Phillips, R. T., Phlaum, S., Pieters, D., Pineau, J., Pinter, A., Pinto, F., Pisters, R., Pivac, N., Pocanic, D., Podoleanu, C., Politano, A., Poljakovic, Z., Pollock, S., Garcea, J. P., Poppert, H., Porcu, M., Reino, A. P., Prasad, N., Precoma, D. B., Prelle, A., Prodafikas, J., Protasov, K., Pye, M., Qiu, Z., Quedillac, J. -M., Raev, D., Raffo Grado, C. A., Rahimi, S., Raisaro, A., Rama, B., Ramos, R., Ranieri, M., Raposo, N., Rashba, E., Rauch-Kroehnert, U., Reddy, R., Renda, G., Reza, S., Ria, L., Richter, D., Rickli, H., Rieker, W., Vera, T. R., Ritt, L. E., Roberts, D., Briones, I. R., Rodriguez Escudero, A. E., Pascual, C. R., Roman, M., Romeo, F., Ronner, E., Roux, J. -F., Rozkova, N., Rubacek, M., Rubalcava, F., Russo, A. M., Rutgers, M. P., Rybak, K., Said, S., Sakamoto, T., Salacata, A., Salem, A., Bodes, R. S., Saltzman, M. A., Salvioni, A., Vallejo, G. S., Fernandez, M. S., Saporito, W. F., Sarikonda, K., Sasaoka, T., Sati, H., Savelieva, I., Scala, P. -J., Schellinger, P., Scherr, C., Schmitz, L., Schmitz, K. -H., Schmitz, B., Schnabel, T., Schnupp, S., Schoeniger, P., Schon, N., Schwimmbeck, P., Seamark, C., Searles, G., Seidl, K. -H., Seidman, B., Sek, J., Sekaran, L., Serrati, C., Shah, N., Shah, V., Shah, A., Shah, S., Sharma, V. K., Shaw, L., Sheikh, K. H., Shimizu, N., Shimomura, H., Shin, D. -G., Shin, E. -S., Shite, J., Sibilio, G., Silver, F., Sime, I., Simmers, T. A., Singh, N., Siostrzonek, P., Smadja, D., Smith, D. W., Snitman, M., Filho, D. S., Soda, H., Sofley, C., Sokal, A., Oi Yan, Y. S., Sotolongo, R., Ferreira de Souza, O., Sparby, J. A., Spinar, J., Sprigings, D., Spyropoulos, A. C., Stakos, D., Steinwender, C., Stergiou, G., Stiell, I., Stoddard, M., Stoikov, A., Streb, W., Styliadis, I., Su, G., Su, X., Sudnik, W., Sukles, K., Sun, X., Swart, H., Szavits-Nossan, J., Taggeselle, J., Takagi, Y., Singh Takhar, A. P., Tamm, A., Tanaka, K., Tanawuttiwat, T., Tang, S., Tang, A., Tarsi, G., Tassinari, T., Tayal, A., Tayebjee, M., Berg, J. M. T., Tesloianu, D., The, S. H. K., Thomas, D., Timsit, S., Tobaru, T., Tomasik, A. R., Torosoff, M., Touze, E., Trendafilova, E., Tsai, W. K., Tse, H. F., Tsutsui, H., Tu, T. M., Tuininga, Y., Turakhia, M., Turk, S., Tcurner, W., Tveit, A., Tytus, R., Valadao, C., van Bergen, P. F. M. M., van de Borne, P., van den Berg, B. J., van der Zwaan, C., Van Eck, M., Vanacker, P., Vasilev, D., Vasilikos, V., Vasilyev, M., Veerareddy, S., Mino, M. V., Venkataraman, A., Verdecchia, P., Versaci, F., Vester, E. G., Vial, H., Victory, J., Villamil, A., Vincent, M., Vlastaris, A., Dahl, J. V., Vora, K., Vranian, R. B., Wakefield, P., Wang, N., Wang, M., Wang, X., Wang, F., Wang, T., Warner, A. L., Watanabe, K., Wei, J., Weimar, C., Weiner, S., Weinrich, R., Wen, M. -S., Wiemer, M., Wiggers, P., Wilke, A., Williams, D., Williams, M. L., Witzenbichler, B., Wong, B., Lawrence Wong, K. S., Wozakowska-Kaplon, B., Wu, S., Wu, R. C., Wunderlich, S., Wyatt, N., Wylie, J. J., Xu, Y., Xu, X., Yamanoue, H., Yamashita, T., Bryan Yan, P. Y., Yang, T., Yao, J., Yeh, K. -H., Yin, W. H., Yotov, Y., Zahn, R., Zarich, S., Zenin, S., Zeuthen, E. L., Zhang, H., Zhang, D., Zhang, X., Zhang, P., Zhang, J., Zhao, S. P., Zhao, Y., Zhao, Z., Zheng, Y., Zhou, J., Zimmermann, S., Zini, A., Zizzo, S., Zong, W., Zukerman, L. S., and Crea F. (ORCID:0000-0001-9404-8846)

Abstract

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007.

Published
2021

25. Monoamine Transporters

Author

Lin, Zhicheng, primary, Canales, Juan J., additional, Björgvinsson, Thröstur, additional, Thomsen, Morgane, additional, Qu, Hong, additional, Liu, Qing-Rong, additional, Torres, Gonzalo E., additional, and Caine, S. Barak, additional

Published
2011
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37. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.

Author

Jung S., van Dam-Nolen D.H.K., Douven E., Delgado-Mederos, R., Marin R., Camps-Renom P., Guisado-Alonso D., Nunez F., Medrano-Martorell S., Merino E., Iida K., Ikeda S., Nishihara M., Irie H., Demirelli D.S., Medanta J.M., Zerna C., Hernandez M.V., Armitage P., Heye A., Munoz-Maniega S., Sakka E., Thrippleton M., Dennis M., Beigneux Y., Silva M., Venketasubramanian N., Ho S.L., Cheung R.T.F., Chan K.H., Teo K.C., Hui E., Kwan J.S.K., Chang R., Tse M.Y., Hoi C.P., Chan C.Y., Chan O.L., Cheung R.H.K., Wong E.K.M., Leung K.T., Tsang S.F., Ip H.L., Ma S.H., Ma K., Fong W.C., Li S.H., Li R., Ng P.W., Wong K.K., Liu W., Wong L., Ramos L., De Schryver E., Jobsis J., van der Sande J., Brouwers P., Roos Y., Stam J., Bakker S., Verbiest H., Schoonewille W., Linn C., Hertzberger L., van Gemert M., Berntsen P., Hendrikse J., Nederkoorn P., Mess W., Koudstaal P., Leff A., Ward N., Nachev P., Perry R., Ozkan H., Mitchell J., Wilson D., Ambler G., Lee K.-J., Lim J.-S., Shiozawa M., Koga M., Li L., Lovelock C., Chabriat H., Hennerici M., Wong Y.K., Mak H.K.F., Prats-Sanchez L., Martinez-Domeno A., Inamura S., Yoshifuji K., Arsava E.M., Horstmann S., Purrucker J., Lam B.Y.K., Wong A., Kim Y.D., Song T.-J., Schrooten M., Lemmens R., Eppinger S., Gattringer T., Uysal E., Tanriverdi Z., Bornstein N.M., Assayag E.B., Hallevi H., Tanaka J., Hara H., Coutts S.B., Hert L., Polymeris A., Seiffge D.J., Lyrer P., Algra A., Kappelle J., Al-Shahi Salman R., Jager H.R., Lip G.Y.H., Mattle H.P., Panos L.D., Mas J.-L., Legrand L., Karayiannis C., Phan T., Gunkel S., Christ N., Abrigo J., Leung T., Chu W., Chappell F., Makin S., Hayden D., Williams D.J., Kooi M.E., Barbato C., Browning S., Wiegertjes K., Tuladhar A.M., Maaijwee N., Guevarra C., Yatawara C., Mendyk A.-M., Delmaire C., Kohler S., van Oostenbrugge R., Zhou Y., Xu C., Hilal S., Gyanwali B., Chen C., Lou M., Staals J., Bordet R., Kandiah N., de Leeuw F.-E., Simister R., van der Lugt A., Kelly P.J., Wardlaw J.M., Soo Y., Fluri F., Srikanth V., Calvet D., Kwa V.I.H., Engelter S.T., Peters N., Smith E.E., Yakushiji Y., Orken D.N., Fazekas F., Thijs V., Heo J.H., Mok V., Veltkamp R., Ay H., Imaizumi T., Gomez-Anson B., Lau K.K., Jouvent E., Rothwell P.M., Toyoda K., Bae H.-J., Marti-Fabregas J., Werring D.J., Harkness K., Shaw L., Sword J., Mohd Nor A., Sharma P., Kelly D., Harrington F., Randall M., Smith M., Mahawish K., Elmarim A., Esisi B., Cullen C., Nallasivam A., Price C., Barry A., Roffe C., Coyle J., Hassan A., Birns J., Cohen D., Sekaran L., Parry-Jones A., Parry A., Hargroves D., Proschel H., Datta P., Darawil K., Manoj A., Burn M., Patterson C., Giallombardo E., Smyth N., Mansoor S., Anwar I., Marsh R., Ispoglou S., Chadha D., Prabhakaran M., Meenakishundaram S., O'Connell J., Scott J., Krishnamurthy V., Aghoram P., McCormick M., Sprigg N., O'Mahony P., Cooper M., Choy L., Wilkinson P., Leach S., Caine S., Burger I., Gunathilagan G., Guyler P., Emsley H., Davis M., Manawadu D., Pasco K., Mamun M., Luder R., Sajid M., Okwera J., Warburton E., Saastamoinen K., England T., Putterill J., Flossman E., Power M., Dani K., Mangion D., Suman A., Corrigan J., Lawrence E., Vahidassr D., Shakeshaft C., Brown M., Charidimou A., Cohen H., Banerjee G., Houlden H., White M., Yousry T., Flossmann E., Muir K., El-Koussy M., Gratz P., Molad J., Korczyn A., Kliper E., Maeder P., Gass A., Pachai C., Bracoub L., Douste-Blazy M.-Y., Fratacci M.D., Vicaut E., Sato S., Miwa K., Fujita K., Ide T., Ma H., Ly J., Singhal S., Chandra R., Slater L.-A., Soufan C., Moran C., Traenka C., Thilemann S., Fladt J., Gensicke H., Bonati L., Kim B.J., Han M.-K., Kang J., Ko E., Yang M.H., Jang M.S., Murphy S., Carty F., Akijian L., Thornton J., Schembri M., Jung S., van Dam-Nolen D.H.K., Douven E., Delgado-Mederos, R., Marin R., Camps-Renom P., Guisado-Alonso D., Nunez F., Medrano-Martorell S., Merino E., Iida K., Ikeda S., Nishihara M., Irie H., Demirelli D.S., Medanta J.M., Zerna C., Hernandez M.V., Armitage P., Heye A., Munoz-Maniega S., Sakka E., Thrippleton M., Dennis M., Beigneux Y., Silva M., Venketasubramanian N., Ho S.L., Cheung R.T.F., Chan K.H., Teo K.C., Hui E., Kwan J.S.K., Chang R., Tse M.Y., Hoi C.P., Chan C.Y., Chan O.L., Cheung R.H.K., Wong E.K.M., Leung K.T., Tsang S.F., Ip H.L., Ma S.H., Ma K., Fong W.C., Li S.H., Li R., Ng P.W., Wong K.K., Liu W., Wong L., Ramos L., De Schryver E., Jobsis J., van der Sande J., Brouwers P., Roos Y., Stam J., Bakker S., Verbiest H., Schoonewille W., Linn C., Hertzberger L., van Gemert M., Berntsen P., Hendrikse J., Nederkoorn P., Mess W., Koudstaal P., Leff A., Ward N., Nachev P., Perry R., Ozkan H., Mitchell J., Wilson D., Ambler G., Lee K.-J., Lim J.-S., Shiozawa M., Koga M., Li L., Lovelock C., Chabriat H., Hennerici M., Wong Y.K., Mak H.K.F., Prats-Sanchez L., Martinez-Domeno A., Inamura S., Yoshifuji K., Arsava E.M., Horstmann S., Purrucker J., Lam B.Y.K., Wong A., Kim Y.D., Song T.-J., Schrooten M., Lemmens R., Eppinger S., Gattringer T., Uysal E., Tanriverdi Z., Bornstein N.M., Assayag E.B., Hallevi H., Tanaka J., Hara H., Coutts S.B., Hert L., Polymeris A., Seiffge D.J., Lyrer P., Algra A., Kappelle J., Al-Shahi Salman R., Jager H.R., Lip G.Y.H., Mattle H.P., Panos L.D., Mas J.-L., Legrand L., Karayiannis C., Phan T., Gunkel S., Christ N., Abrigo J., Leung T., Chu W., Chappell F., Makin S., Hayden D., Williams D.J., Kooi M.E., Barbato C., Browning S., Wiegertjes K., Tuladhar A.M., Maaijwee N., Guevarra C., Yatawara C., Mendyk A.-M., Delmaire C., Kohler S., van Oostenbrugge R., Zhou Y., Xu C., Hilal S., Gyanwali B., Chen C., Lou M., Staals J., Bordet R., Kandiah N., de Leeuw F.-E., Simister R., van der Lugt A., Kelly P.J., Wardlaw J.M., Soo Y., Fluri F., Srikanth V., Calvet D., Kwa V.I.H., Engelter S.T., Peters N., Smith E.E., Yakushiji Y., Orken D.N., Fazekas F., Thijs V., Heo J.H., Mok V., Veltkamp R., Ay H., Imaizumi T., Gomez-Anson B., Lau K.K., Jouvent E., Rothwell P.M., Toyoda K., Bae H.-J., Marti-Fabregas J., Werring D.J., Harkness K., Shaw L., Sword J., Mohd Nor A., Sharma P., Kelly D., Harrington F., Randall M., Smith M., Mahawish K., Elmarim A., Esisi B., Cullen C., Nallasivam A., Price C., Barry A., Roffe C., Coyle J., Hassan A., Birns J., Cohen D., Sekaran L., Parry-Jones A., Parry A., Hargroves D., Proschel H., Datta P., Darawil K., Manoj A., Burn M., Patterson C., Giallombardo E., Smyth N., Mansoor S., Anwar I., Marsh R., Ispoglou S., Chadha D., Prabhakaran M., Meenakishundaram S., O'Connell J., Scott J., Krishnamurthy V., Aghoram P., McCormick M., Sprigg N., O'Mahony P., Cooper M., Choy L., Wilkinson P., Leach S., Caine S., Burger I., Gunathilagan G., Guyler P., Emsley H., Davis M., Manawadu D., Pasco K., Mamun M., Luder R., Sajid M., Okwera J., Warburton E., Saastamoinen K., England T., Putterill J., Flossman E., Power M., Dani K., Mangion D., Suman A., Corrigan J., Lawrence E., Vahidassr D., Shakeshaft C., Brown M., Charidimou A., Cohen H., Banerjee G., Houlden H., White M., Yousry T., Flossmann E., Muir K., El-Koussy M., Gratz P., Molad J., Korczyn A., Kliper E., Maeder P., Gass A., Pachai C., Bracoub L., Douste-Blazy M.-Y., Fratacci M.D., Vicaut E., Sato S., Miwa K., Fujita K., Ide T., Ma H., Ly J., Singhal S., Chandra R., Slater L.-A., Soufan C., Moran C., Traenka C., Thilemann S., Fladt J., Gensicke H., Bonati L., Kim B.J., Han M.-K., Kang J., Ko E., Yang M.H., Jang M.S., Murphy S., Carty F., Akijian L., Thornton J., and Schembri M.

Abstract

Background: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. Method(s): We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. Finding(s): Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1.34 years [IQR 0.19-2.44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1.35 (95% CI 1.20-1.50) for the composite outcome of

Published
2019

38. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Author

Wilson, D. (Duncan), Ambler, G. (Gareth), Lee, K.-J. (Keon-Joo), Lim, J.-S. (Jae-Sung), Shiozawa, M. (Masayuki), Koga, M. (Masatoshi), Li, L. (Linxin), Lovelock, C. (Caroline), Chabriat, H. (Hugues), Hennerici, M.G. (Michael), Wong, Y.K. (Yuen Kwun), Mak, H.K.F. (Henry Ka Fung), Prats-Sánchez, L. (Luis), Martínez-Domeño, A. (Alejandro), Inamura, S. (Shigeru), Yoshifuji, K. (Kazuhisa), Arsava, E.M. (Ethem Murat), Horstmann, S. (Solveig), Purrucker, J. (Jan), Lam, B.Y.K. (Bonnie Yin Ka), Wong, A. (Adrian), Kim, Y.D. (Young Dae), Song, T.-J. (Tae-Jin), Schrooten, M. (Maarten), Lemmens, R. (Robin), Eppinger, S. (Sebastian), Gattringer, T. (Thomas), Uysal, E. (Ender), Tanriverdi, Z. (Zeynep), Bornstein, S.R. (Stefan), Assayag, E.B. (Einor Ben), Hallevi, H. (Hen), Tanaka, J. (Jun), Hara, H. (Hideo), Coutts, S.B. (Shelagh B), Hert, L. (Lisa), Polymeris, A. (Alexandros), Seiffge, D.J. (David J), Lyrer, P.A. (Philippe), Algra, A. (Ale), Kappelle, L.J. (Jaap), Al-Shahi Salman, R. (Rustam), Jäger, H.R. (Rolf), Lip, G.Y.H. (Gregory Y H), Mattle, H., Panos, L.D. (Leonidas D), Mas, J.L. (J.), Legrand, L. (Laurence), Karayiannis, C. (Christopher), Phan, T.G. (Thanh), Gunkel, S. (Sarah), Christ, N. (Nicolas), Abrigo, J. (Jill), Leung, T. (Thomas), Chu, W. (Winnie), Chappell, F. (Francesca), Makin, S. (Stephen), Hayden, D. (Derek), Williams, D.J. (David J), Kooi, M.E. (M. Eline), van Dam-Nolen, D.H.K. (Dianne H K), Barbato, C. (Carmen), Browning, S. (Simone), Wiegertjes, K. (Kim), Tuladhar, A.M. (Anil M.), Maaijwee, N. (Noortje), Guevarra, C. (Christine), Yatawara, C. (Chathuri), Mendyk, A.-M. (Anne-Marie), Delmaire, C. (Christine), Köhler, S. (Sebastian), Oostenbrugge, R.J. (Robert) van, Zhou, Y. (Ying), Xu, C. (Chao), Hilal, S. (Saima), Gyanwali, B. (Bibek), Chen, C. (Christopher), Lou, M. (Min), Staals, J. (Julie), Bordet, R. (Régis), Kandiah, N. (Nagaendran), Leeuw, H.F. (Frank) de, Simister, R. (Robert), Lugt, A. (Aad) van der, Kelly, P.J. (Peter J), Wardlaw, J.M. (J.), Soo, Y. (Yannie), Fluri, F. (Felix), Srikanth, V. (Velandai), Calvet, D. (David), Jung, S. (Simon), Kwa, V.I.H., Engelter, S.T. (Stefan), Peters, N. (Nils), Smith, E.E. (Eric), Yakushiji, Y. (Yusuke), Orken, D.N. (Dilek Necioglu), Fazekas, F. (Franz), Thijs, V. (Vincent), Heo, J.H. (Ji Hoe), Mok, V. (Vincent), Veltkamp, R. (Roland), Ay, H. (Hakan), Imaizumi, T. (Toshio), Gomez-Anson, B. (Beatriz), Lau, K.K. (Kui Kai), Jouvent, E. (Eric), Rothwell, P.M. (Peter), Toyoda, K. (Kazunori), Bae, H.-J. (Hee-Joon), Marti-Fabregas, J. (Joan), Werring, D.J. (David), Harkness, K. (Kirsty), Shaw, L. (Louise), Sword, J. (Jane), Mohd Nor, A. (Azlisham), Sharma, P. (Pankaj), Kelly, D. (Deborah), Harrington, F. (Frances), Randall, M. (Marc), Smith, M. (Matthew), Mahawish, K. (Karim), Elmarim, A. (Abduelbaset), Esisi, B. (Bernard), Cullen, C. (Claire), Nallasivam, A. (Arumug), Price, C. (Christopher), Barry, A. (Adrian), Roffe, C. (Christine), Coyle, J. (John), Hassan, A. (Ahamad), Birns, J. (Jonathan), Cohen, D. (David), Sekaran, L. (Lakshmanan), Parry-Jones, A. (Adrian), Parry, A. (Anthea), Hargroves, D. (David), Proschel, H. (Harald), Datta, P. (Prabel), Darawil, K. (Khaled), Manoj, A. (Aravindakshan), Burn, M. (Mathew), Patterson, C. (Chris), Giallombardo, E. (Elio), Smyth, N. (Nigel), Mansoor, S. (Syed), Anwar, I. (Ijaz), Marsh, R. (Rachel), Ispoglou, S. (Sissi), Chadha, D. (Dinesh), Prabhakaran, M. (Mathuri), Meenakishundaram, S. (Sanjeevikumar), O'Connell, J. (Janice), Scott, J. (Jon), Krishnamurthy, V. (Vinodh), Aghoram, P. (Prasanna), McCormick, M. (Michael), Sprigg, N. (Nikola), O'Mahony, P. (Paul), Cooper, M. (Martin), Choy, L. (Lillian), Wilkinson, P. (Peter), Leach, S. (Simon), Caine, S. (Sarah), Burger, I. (Ilse), Gunathilagan, G. (Gunaratam), Guyler, P. (Paul), Emsley, H. (Hedley), Davis, M. (Michelle), Manawadu, D. (Dulka), Pasco, K. (Kath), Mamun, M. (Maam), Luder, R. (Robert), Sajid, M. (Mahmud), Okwera, J. (James), Warburton, E. (Elizabeth), Saastamoinen, K. (Kari), England, T. (Timothy), Putterill, J. (Janet), Flossman, E. (Enrico), Power, M. (Michael), Dani, K. (Krishna), Mangion, D. (David), Suman, A. (Appu), Corrigan, J. (John), Lawrence, E. (Enas), Vahidassr, D. (Djamil), Shakeshaft, C. (Clare), Brown, M. (Martin), Charidimou, A. (Andreas), Cohen, H. (Hannah), Banerjee, G. (Gargi), Houlden, H. (Henry), White, M. (Mark), Yousry, T. (Tarek), Flossmann, E. (Enrico), Muir, K. (Keith), El-Koussy, M. (Marwan), Gratz, P. (Pascal), Molad, J. (Jeremy), Korczyn, A.D. (A.), Kliper, E. (Efrat), Maeder, P. (Philippe), Gass, A. (Achim), Pachai, C. (Chahin), Bracoub, L. (Luc), Douste-Blazy, M.-Y. (Marie-Yvonne), Fratacci, M.D. (Marie Dominique), Vicaut, E. (Eric), Sato, S. (Shoichiro), Miwa, K. (Kaori), Fujita, K. (Kyohei), Ide, T. (Toshihiro), Ma, H. (Henry), Ly, J. (John), Singhal, S. (Shahoo), Chandra, R. (Ronil), Slater, L.-A. (Lee-Anne), Soufan, C. (Cathy), Moran, C. (Christopher), Traenka, C. (Christopher), Thilemann, S. (Sebastian), Fladt, J. (Joachim), Gensicke, H. (Henrik), Bonati, L. (Leo), Kim, B.J. (Beom Joon), Han, M.-K. (Moon-Ku), Kang, J. (Jihoon), Ko, E. (Eunbin), Yang, M.H. (Mi Hwa), Jang, M.S. (Myung Suk), Murphy, S. (Sean), Carty, F. (Fiona), Akijian, L. (Layan), Thornton, J. (John), Schembri, M. (Mark), Douven, E. (Elles), Delgado-Mederos;, R. (Raquel), Marín, R. (Rebeca), Camps-Renom, P. (Pol), Guisado-Alonso, D. (Daniel), Nuñez, F. (Fidel), Medrano-Martorell, S. (Santiago), Merino, E. (Elisa), Iida, K. (Kotaro), Ikeda, S. (Syuhei), Nishihara, M. (Masashi), Irie, H. (Hiroyuki), Demirelli, D.S. (Derya Selcuk), Medanta, J.M. (Jayesh Modi), Zerna, C. (Charlotte), Hernández, M.V. (Maria Valdés), Armitage, P. (Paul), Heye, A. (Anna), Muñoz Maniega, S. (Susana), Sakka, E. (Eleni), Thrippleton, M. (Michael), Dennis, M.S. (M.), Beigneux, Y. (Ysoline), Silva, M. (Mauro), Venketasubramanian, N. (Narayanaswamy), Ho, S.L. (Shu Leung), Cheung, R.T.F. (Raymond Tak Fai), Chan, K.H. (Koon Ho), Teo, K.C. (Kay Cheong), Hui, E. (Edward), Kwan, J.S.K. (Joseph Shiu Kwong), Chang, R. (Richard), Tse, M.Y. (Man Yu), Hoi, C.P. (Chu Peng), Chan, C.Y. (Chung Yan), Chan, O.L. (Oi Ling), Cheung, R.H.K. (Ryan Hoi Kit), Wong, E.K.M. (Edmund Ka Ming), Leung, K.T. (Kam Tat), Tsang, S.F. (Suk Fung), Ip, H.L. (Hing Lung), Ma, S.H. (Sze Ho), Ma, K. (Karen), Fong, W.C. (Wing Chi), Li, S.H. (Siu Hung), Li, R. (Richard), Ng, P.W. (Ping Wing), Wong, K.K. (Kwok Kui), Liu, W. (Wenyan), Wong, L. (Lawrence), Ramos, L. (Lino), Schryver, E.L.L.M. (Els) de, Jöbsis, J. (Joost), van der Sande, J. (Jaap), Brouwers, P.J. (Paul), Roos, Y.B.W.E.M. (Yvo), Stam, J. (Jan), Bakker, S.L.M. (Stef), Verbiest, H. (Henk), Schoonewille, W. (Wouter), Linn, C. (Cisca), Hertzberger, L., Gemert, M. (Maarten) van, Berntsen, P. (Paul), Hendrikse, J. (Jeroen), Nederkoorn, P.J. (Paul), Mess, W.H. (Werner), Koudstaal, P.J. (Peter), Leff, A. (Alexander), Ward, N. (Nicholas), Nachev, P. (Parashkev), Perry, R. (Richard), Ozkan, H. (Hatice), Mitchell, J. (John), Wilson, D. (Duncan), Ambler, G. (Gareth), Lee, K.-J. (Keon-Joo), Lim, J.-S. (Jae-Sung), Shiozawa, M. (Masayuki), Koga, M. (Masatoshi), Li, L. (Linxin), Lovelock, C. (Caroline), Chabriat, H. (Hugues), Hennerici, M.G. (Michael), Wong, Y.K. (Yuen Kwun), Mak, H.K.F. (Henry Ka Fung), Prats-Sánchez, L. (Luis), Martínez-Domeño, A. (Alejandro), Inamura, S. (Shigeru), Yoshifuji, K. (Kazuhisa), Arsava, E.M. (Ethem Murat), Horstmann, S. (Solveig), Purrucker, J. (Jan), Lam, B.Y.K. (Bonnie Yin Ka), Wong, A. (Adrian), Kim, Y.D. (Young Dae), Song, T.-J. (Tae-Jin), Schrooten, M. (Maarten), Lemmens, R. (Robin), Eppinger, S. (Sebastian), Gattringer, T. (Thomas), Uysal, E. (Ender), Tanriverdi, Z. (Zeynep), Bornstein, S.R. (Stefan), Assayag, E.B. (Einor Ben), Hallevi, H. (Hen), Tanaka, J. (Jun), Hara, H. (Hideo), Coutts, S.B. (Shelagh B), Hert, L. (Lisa), Polymeris, A. (Alexandros), Seiffge, D.J. (David J), Lyrer, P.A. (Philippe), Algra, A. (Ale), Kappelle, L.J. (Jaap), Al-Shahi Salman, R. (Rustam), Jäger, H.R. (Rolf), Lip, G.Y.H. (Gregory Y H), Mattle, H., Panos, L.D. (Leonidas D), Mas, J.L. (J.), Legrand, L. (Laurence), Karayiannis, C. (Christopher), Phan, T.G. (Thanh), Gunkel, S. (Sarah), Christ, N. (Nicolas), Abrigo, J. (Jill), Leung, T. (Thomas), Chu, W. (Winnie), Chappell, F. (Francesca), Makin, S. (Stephen), Hayden, D. (Derek), Williams, D.J. (David J), Kooi, M.E. (M. Eline), van Dam-Nolen, D.H.K. (Dianne H K), Barbato, C. (Carmen), Browning, S. (Simone), Wiegertjes, K. (Kim), Tuladhar, A.M. (Anil M.), Maaijwee, N. (Noortje), Guevarra, C. (Christine), Yatawara, C. (Chathuri), Mendyk, A.-M. (Anne-Marie), Delmaire, C. (Christine), Köhler, S. (Sebastian), Oostenbrugge, R.J. (Robert) van, Zhou, Y. (Ying), Xu, C. (Chao), Hilal, S. (Saima), Gyanwali, B. (Bibek), Chen, C. (Christopher), Lou, M. (Min), Staals, J. (Julie), Bordet, R. (Régis), Kandiah, N. (Nagaendran), Leeuw, H.F. (Frank) de, Simister, R. (Robert), Lugt, A. (Aad) van der, Kelly, P.J. (Peter J), Wardlaw, J.M. (J.), Soo, Y. (Yannie), Fluri, F. (Felix), Srikanth, V. (Velandai), Calvet, D. (David), Jung, S. (Simon), Kwa, V.I.H., Engelter, S.T. (Stefan), Peters, N. (Nils), Smith, E.E. (Eric), Yakushiji, Y. (Yusuke), Orken, D.N. (Dilek Necioglu), Fazekas, F. (Franz), Thijs, V. (Vincent), Heo, J.H. (Ji Hoe), Mok, V. (Vincent), Veltkamp, R. (Roland), Ay, H. (Hakan), Imaizumi, T. (Toshio), Gomez-Anson, B. (Beatriz), Lau, K.K. (Kui Kai), Jouvent, E. (Eric), Rothwell, P.M. (Peter), Toyoda, K. (Kazunori), Bae, H.-J. (Hee-Joon), Marti-Fabregas, J. (Joan), Werring, D.J. (David), Harkness, K. (Kirsty), Shaw, L. (Louise), Sword, J. (Jane), Mohd Nor, A. (Azlisham), Sharma, P. (Pankaj), Kelly, D. (Deborah), Harrington, F. (Frances), Randall, M. (Marc), Smith, M. (Matthew), Mahawish, K. (Karim), Elmarim, A. (Abduelbaset), Esisi, B. (Bernard), Cullen, C. (Claire), Nallasivam, A. (Arumug), Price, C. (Christopher), Barry, A. (Adrian), Roffe, C. (Christine), Coyle, J. (John), Hassan, A. (Ahamad), Birns, J. (Jonathan), Cohen, D. (David), Sekaran, L. (Lakshmanan), Parry-Jones, A. (Adrian), Parry, A. (Anthea), Hargroves, D. (David), Proschel, H. (Harald), Datta, P. (Prabel), Darawil, K. (Khaled), Manoj, A. (Aravindakshan), Burn, M. (Mathew), Patterson, C. (Chris), Giallombardo, E. (Elio), Smyth, N. (Nigel), Mansoor, S. (Syed), Anwar, I. (Ijaz), Marsh, R. (Rachel), Ispoglou, S. (Sissi), Chadha, D. (Dinesh), Prabhakaran, M. (Mathuri), Meenakishundaram, S. (Sanjeevikumar), O'Connell, J. (Janice), Scott, J. (Jon), Krishnamurthy, V. (Vinodh), Aghoram, P. (Prasanna), McCormick, M. (Michael), Sprigg, N. (Nikola), O'Mahony, P. (Paul), Cooper, M. (Martin), Choy, L. (Lillian), Wilkinson, P. (Peter), Leach, S. (Simon), Caine, S. (Sarah), Burger, I. (Ilse), Gunathilagan, G. (Gunaratam), Guyler, P. (Paul), Emsley, H. (Hedley), Davis, M. (Michelle), Manawadu, D. (Dulka), Pasco, K. (Kath), Mamun, M. (Maam), Luder, R. (Robert), Sajid, M. (Mahmud), Okwera, J. (James), Warburton, E. (Elizabeth), Saastamoinen, K. (Kari), England, T. (Timothy), Putterill, J. (Janet), Flossman, E. (Enrico), Power, M. (Michael), Dani, K. (Krishna), Mangion, D. (David), Suman, A. (Appu), Corrigan, J. (John), Lawrence, E. (Enas), Vahidassr, D. (Djamil), Shakeshaft, C. (Clare), Brown, M. (Martin), Charidimou, A. (Andreas), Cohen, H. (Hannah), Banerjee, G. (Gargi), Houlden, H. (Henry), White, M. (Mark), Yousry, T. (Tarek), Flossmann, E. (Enrico), Muir, K. (Keith), El-Koussy, M. (Marwan), Gratz, P. (Pascal), Molad, J. (Jeremy), Korczyn, A.D. (A.), Kliper, E. (Efrat), Maeder, P. (Philippe), Gass, A. (Achim), Pachai, C. (Chahin), Bracoub, L. (Luc), Douste-Blazy, M.-Y. (Marie-Yvonne), Fratacci, M.D. (Marie Dominique), Vicaut, E. (Eric), Sato, S. (Shoichiro), Miwa, K. (Kaori), Fujita, K. (Kyohei), Ide, T. (Toshihiro), Ma, H. (Henry), Ly, J. (John), Singhal, S. (Shahoo), Chandra, R. (Ronil), Slater, L.-A. (Lee-Anne), Soufan, C. (Cathy), Moran, C. (Christopher), Traenka, C. (Christopher), Thilemann, S. (Sebastian), Fladt, J. (Joachim), Gensicke, H. (Henrik), Bonati, L. (Leo), Kim, B.J. (Beom Joon), Han, M.-K. (Moon-Ku), Kang, J. (Jihoon), Ko, E. (Eunbin), Yang, M.H. (Mi Hwa), Jang, M.S. (Myung Suk), Murphy, S. (Sean), Carty, F. (Fiona), Akijian, L. (Layan), Thornton, J. (John), Schembri, M. (Mark), Douven, E. (Elles), Delgado-Mederos;, R. (Raquel), Marín, R. (Rebeca), Camps-Renom, P. (Pol), Guisado-Alonso, D. (Daniel), Nuñez, F. (Fidel), Medrano-Martorell, S. (Santiago), Merino, E. (Elisa), Iida, K. (Kotaro), Ikeda, S. (Syuhei), Nishihara, M. (Masashi), Irie, H. (Hiroyuki), Demirelli, D.S. (Derya Selcuk), Medanta, J.M. (Jayesh Modi), Zerna, C. (Charlotte), Hernández, M.V. (Maria Valdés), Armitage, P. (Paul), Heye, A. (Anna), Muñoz Maniega, S. (Susana), Sakka, E. (Eleni), Thrippleton, M. (Michael), Dennis, M.S. (M.), Beigneux, Y. (Ysoline), Silva, M. (Mauro), Venketasubramanian, N. (Narayanaswamy), Ho, S.L. (Shu Leung), Cheung, R.T.F. (Raymond Tak Fai), Chan, K.H. (Koon Ho), Teo, K.C. (Kay Cheong), Hui, E. (Edward), Kwan, J.S.K. (Joseph Shiu Kwong), Chang, R. (Richard), Tse, M.Y. (Man Yu), Hoi, C.P. (Chu Peng), Chan, C.Y. (Chung Yan), Chan, O.L. (Oi Ling), Cheung, R.H.K. (Ryan Hoi Kit), Wong, E.K.M. (Edmund Ka Ming), Leung, K.T. (Kam Tat), Tsang, S.F. (Suk Fung), Ip, H.L. (Hing Lung), Ma, S.H. (Sze Ho), Ma, K. (Karen), Fong, W.C. (Wing Chi), Li, S.H. (Siu Hung), Li, R. (Richard), Ng, P.W. (Ping Wing), Wong, K.K. (Kwok Kui), Liu, W. (Wenyan), Wong, L. (Lawrence), Ramos, L. (Lino), Schryver, E.L.L.M. (Els) de, Jöbsis, J. (Joost), van der Sande, J. (Jaap), Brouwers, P.J. (Paul), Roos, Y.B.W.E.M. (Yvo), Stam, J. (Jan), Bakker, S.L.M. (Stef), Verbiest, H. (Henk), Schoonewille, W. (Wouter), Linn, C. (Cisca), Hertzberger, L., Gemert, M. (Maarten) van, Berntsen, P. (Paul), Hendrikse, J. (Jeroen), Nederkoorn, P.J. (Paul), Mess, W.H. (Werner), Koudstaal, P.J. (Peter), Leff, A. (Alexander), Ward, N. (Nicholas), Nachev, P. (Parashkev), Perry, R. (Richard), Ozkan, H. (Hatice), and Mitchell, J. (John)

Abstract

Background: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. Methods: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or

Published
2019
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39. Elemental characterisation of the pyramidal neuron layer within the rat and mouse hippocampus

Author

Hackett, Mark, Hollings, A., Caine, S., Bewer, Brian, Alaverdashvili, Mariam, Takechi, Ryu, Mamo, John, Jones, Michael, de Jonge, Martin, Paterson, Phyllis, Pickering, Ingrid, George, Graham, Hackett, Mark, Hollings, A., Caine, S., Bewer, Brian, Alaverdashvili, Mariam, Takechi, Ryu, Mamo, John, Jones, Michael, de Jonge, Martin, Paterson, Phyllis, Pickering, Ingrid, and George, Graham

Abstract

A unique combination of sensitivity, resolution, and penetration make X-ray fluorescence imaging (XFI) ideally suited to investigate trace elemental distributions in the biological context. XFI has gained widespread use as an analytical technique in the biological sciences, and in particular enables exciting new avenues of research in the field of neuroscience. In this study, elemental mapping by XFI was applied to characterise the elemental content within neuronal cell layers of hippocampal sub-regions of mice and rats. Although classical histochemical methods for metal detection exist, such approaches are typically limited to qualitative analysis. Specifically, histochemical methods are not uniformly sensitive to all chemical forms of a metal, often displaying variable sensitivity to specific “pools” or chemical forms of a metal. In addition, histochemical methods require fixation and extensive chemical treatment of samples, creating the strong likelihood for metal redistribution, leaching, or contamination. Direct quantitative elemental mapping of total elemental pools, in situ within ex vivo tissue sections, without the need for chemical fixation or addition of staining reagents is not possible with traditional histochemical methods; however, such a capability, which is provided by XFI, can offer an enormous analytical advantage. The results we report herein demonstrate the analytical advantage of XFI elemental mapping for direct, label-free metal quantification, in situ within ex vivo brain tissue sections. Specifically, we definitively characterise for the first time, the abundance of Fe within the pyramidal cell layers of the hippocampus. Localisation of Fe to this cell layer is not reproducibly achieved with classical Perls histochemical Fe stains. The ability of XFI to directly quantify neuronal elemental (P, S, Cl, K, Ca, Fe, Cu, Zn) distributions, revealed unique profiles of Fe and Zn within anatomical sub-regions of the hippocampus i.e., cornu ammonis 1

Published
2019

42. Neurobiology of drug addiction.

Author

Koob, George F., primary, Caine, S. Barak, additional, Hyytia, Petri, additional, Markou, Athina, additional, Parsons, Loren H., additional, Roberts, Amanda J., additional, Schulteis, Gery, additional, and Weiss, Friedbert, additional

Published
1999
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48. Mutations in CalDAG-GEFI Lead to Striatal Signaling Deficits and Psychomotor Symptoms in Multiple Species Including Human

Author

Crittenden, Jill R., primary, Sauvage, Magdalena, additional, Kitsukawa, Takashi, additional, Burguière, Eric, additional, Cepeda, Carlos, additional, André, Véronique M., additional, Canault, Matthias, additional, Thomsen, Morgane, additional, Zhang, Hui, additional, Costa, Cinzia, additional, Martella, Giuseppina, additional, Ghiglieri, Veronica, additional, Pescatore, Karen A., additional, Unterwald, Ellen M., additional, Jackson, Walker, additional, Housman, David E., additional, Caine, S. Barak, additional, Sulzer, David, additional, Calabresi, Paolo, additional, Levine, Michael S., additional, Brefel-Courbon, Christine, additional, Smith, Anne C., additional, Alessi, Marie-Christine, additional, Azulay, Jean-Phillipe, additional, and Graybiel, Ann M., additional

Published
2019
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