المؤلفون: Stuebler, Martin, Manzer, Zachary A., Liu, Han-Yuan, Miller, Julia, Richter, Annett, Krishnan, Srinivasan, Selivanovitch, Ekaterina, Banuna, Barituziga, Jander, Georg, Reimhult, Erik, Zipfel, Warren R., Roeder, Adrienne H. K., Piñeros, Miguel A., Daniel, Susan

المصدر: ACS Applied Materials & Interfaces; 4/24/2024, Vol. 16 Issue 16, p20092-20104, 13p

المؤلفون: Stuebler, Hermann, Kraehmer, Hansjoerg

المصدر: Julius-Kühn-Archiv, Iss 434, Pp 15-19 (2012)

مصطلحات موضوعية: biodiversity, changes in crop husbandry, landscape management, rare weeds, regulation on plant protection products, weed resistance, Agriculture, Botany, QK1-989

الوصف: Crop production has become very efficient in developed countries. One factor that has contributed to this success is modern weed control tools. Cropping practices have changed considerably within the last century. Today, spring crops are grown on a much smaller scale in Europe than a hundred years ago. Oats and potatoes are minor crops whereas winter cereals and maize have become the most important crops of European agriculture. This fact combined with a high amount of manure from animal production had a much greater impact on biodiversity than herbicides. Efficient herbicides have been used against a number of weed species such as blackgrass or mayweed in cereals or barnyardgrass and lambsquarters in maize for almost forty years. None of these major weed problems, however, has disappeared. Weed species have physiologically adapted and have become resistant. The application of Council directive 91/414/EEC has resulted in a reduction of production tools for the farmer. With the implementation of regulation EC 1107/2009 it can be expected that the number of active ingredients available to the farmer will be even more decreased. Also, the development of new herbicides will become more difficult for agrochemical companies. Farmers will have less tools to control weeds and will face a drastic increase of resistance problems. In consequence, ploughing and other mechanical tools will become necessary resulting in higher production costs and more economic pressure on farmers.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1868-9892Test

الوصول الحر: https://doaj.org/article/502ae090053a4aa3a007e3ddf88ce0b0Test

المؤلفون: Giel, K, Binkele, M, Stübler, P, Zipfel, S, Enck, P

المصدر: 1. Kongress der Deutschen Gesellschaft für Essstörungen e.V. (DGESS); 20071108-20071110; Prien am Chiemsee; DOC07dgessP6 /20071024/

مصطلحات موضوعية: ddc: 610

العلاقة: http://www.egms.de/en/meetings/dgess2007/07dgess80.shtmlTest

الإتاحة: http://www.egms.de/en/meetings/dgess2007/07dgess80.shtmlTest

المؤلفون: le Roux, C., Astrup, A., Fujioka, K., Greenway, F., Lau, D., Van Gaal, L., Ortiz, R., Wilding, J., Skjøth, T., Manning, L., Pi Sunyer, X., Hamann, A., Barakat, A., Blüher, M., Linn, T., Mölle, A., Segner, A., Stübler, P., Tosch Sisting, R., Pacini, F., Santini, F., Marchesini, G., Rotella, C., Invitti, C., Vettor, R., BUSCEMI, Silvio, Raya, P., Freijoo, F., de Barbará, R., Carraro, R., Bobillo, E., de la Cuesta, C., Farsang, C., Csaszar, A., Zahorska Markiewicz, B., Pupek Musialik, D., Franek, E., Ostrowska, L., Olszanecka Glinianowicz, M., Lalic, N., Micic, D., Ludvik, B., Paulweber, B., Prager, R., Scheen, A., Hermansen, K., Madsbad, S., Rissanen, A., Nieminen, S., Savolainen, M., Krempf, M., Romon, M., Laville, M., Marre, M., Mira, R., Finucane, F., Veenendaal, A., van Berkum, F., Johannsson Vidarsdóttir, S., Van de Walle, V., Meesters, E., Hjelmesæth, J., Klemsdal, T., Kulseng, B., Bach Kliegel, B., Laederach, K., Villiger, L., Golay, A., Bilz, S., Sathyapalan, T., Bain, S., Kumar, S., Le Roux, C., Lean, M., Mcgowan, B., Rehman, T., Wittert, G., Caterson, I., Proietto, J., Prins, J., Neto, B., Gross, J., Chacra, A., Halpern, A., de Almeida Suplicy, H., Chow, F., Thacker, H., Chadha, M., Chandalia, H., Unnikrishnan, A., Kalra, S., Deshpande, N., Shunmugavelu, M., Deshmukh, V., Maislos, M., Lieberman, G., Shimon, I., Stern, N., Nabriski, D., Karnieli, E., Shehadeh, N., Gonzalez Galvez, G., del Rosario Arechavaleta Granell, M., Franco, G., Gurieva, I., Suplotova, L., Troshina, E., Ruyatkina, L., Voychik, E., Martsevich, S., Startseva, M., Seeber, M., Badat, A., Ellis, G., Altuntas, Y., Guler, S., Ulgen, E., Delibasi, T., Chetty, T., Hart, R., Janzen, J., Labonte, I., Liutkus, J., O'Keefe, D., Padwal, R., Ransom, T., Tytus, R., Weisnagel, S., Adler, J., Aqua, K., Aronoff, S., Bedel, G., Blevins, T., Blumenau, J., Brockmyre, A., Call, R., Canadas, R., Chaykin, L., Cohen, K., Conrow, J., Davis, M., Downey, H., Drosman, S., Duckor, S., Farmer, H., Farrell, J., Fehnel, S., Finneran, M., Forbes, R., Forker, A., Fredrick, M., Geller, S., Gill, S., Glaser, L., Greco, S., Harper, W., Herman, L., Hoekstra, J., Ingebretsen, R., Ison, R., Jain, R., Kaplan, R., Kaster, S., Haase, G., Kerzner, B., Kirstein, J., Koltun, W., Krieger, D., Lewis, C., Madder, R., Marple, R., Mcdermott, E., Mello, C., Miller, A., Mullen, J., Nardandrea, J., O'Neil, P., Pi Sunyer, F., Pucillo, R., Rhee, C., Redrick, S., Pardini, A., Rothman, J., Rubino, D., Sellers, G., Smith, T., Byars, W., Soufer, J., Sussman, A., Patrick, K., Schramm, E., Van Cleeff, M., Berg, S., Wyatt, H., Simon, J.

المساهمون: le Roux, C., Astrup, A., Fujioka, K., Greenway, F., Lau, D., Van Gaal, L., Ortiz, R., Wilding, J., Skjøth, T., Manning, L., Pi-Sunyer, X., Hamann, A., Barakat, A., Blüher, M., Linn, T., Mölle, A., Segner, A., Stübler, P., Tosch-Sisting, R., Pacini, F., Santini, F., Marchesini, G., Rotella, C., Invitti, C., Vettor, R., Buscemi, S., Raya, P., Freijoo, F., de Barbará, R., Carraro, R., Bobillo, E., de la Cuesta, C., Farsang, C., Csaszar, A., Zahorska-Markiewicz, B., Pupek-Musialik, D., Franek, E., Ostrowska, L., Olszanecka-Glinianowicz, M., Lalic, N., Micic, D., Ludvik, B., Paulweber, B., Prager, R., Scheen, A., Hermansen, K., Madsbad, S., Rissanen, A., Nieminen, S., Savolainen, M., Krempf, M., Romon, M., Laville, M., Marre, M., Mira, R., Finucane, F., Veenendaal, A., van Berkum, F., Johannsson-Vidarsdóttir, S., Van de Walle, V., Meesters, E., Hjelmesæth, J., Klemsdal, T., Kulseng, B., Bach-Kliegel, B., Laederach, K., Villiger, L., Golay, A., Bilz, S., Sathyapalan, T., Bain, S., Kumar, S., Le Roux, C., Lean, M., Mcgowan, B., Rehman, T., Wittert, G., Caterson, I., Proietto, J., Prins, J., Neto, B., Gross, J., Chacra, A., Halpern, A., de Almeida Suplicy, H., Chow, F., Thacker, H., Chadha, M., Chandalia, H., Unnikrishnan, A., Kalra, S., Deshpande, N., Shunmugavelu, M., Deshmukh, V., Maislos, M., Lieberman, G., Shimon, I.

مصطلحات موضوعية: Medicine (all)

الوصف: Background Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/28237263; info:eu-repo/semantics/altIdentifier/wos/WOS:000398345100032; volume:389; issue:10077; firstpage:1399; lastpage:1409; numberofpages:11; journal:THE LANCET; http://hdl.handle.net/10447/227733Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85013371919; http://www.journals.elsevier.com/the-lancetTest/

الإتاحة: https://doi.org/10.1016/S0140-6736Test(17)30069-7
http://hdl.handle.net/10447/227733Test
http://www.journals.elsevier.com/the-lancetTest/

المؤلفون: Hernandez A. F., Green J. B., Janmohamed S., D'Agostino R. B., Granger C. B., Jones N. P., Leiter L. A., Rosenberg A. E., Sigmon K. N., Somerville M. C., Thorpe K. M., McMurray J. J. V., Del Prato S., Califf R. M., Holman R., DeMets D., Riddle M., Goodman S., McGuire D., Alexander K., Devore A., Melloni C., Patel C., Kong D., Bloomfield G., Roe M., Tricoci P., Harrison R., Lopes R., Mathews R., Mehta R., Schuyler Jones W., Vemulapalli S., Povsic T., Eapen Z., Dombrowski K., Kolls B., Jordan D., Ambrosy A., Greene S., Mandawat A., Shavadia J., Cooper L., Sharma A., Guimaraes P., Friedman D., Wilson M., Endsley P., Gentry T., Collier J., Perez K., James K., Roush J., Pope C., Howell C., Johnson M., Bailey M., Cole J., Akers T., Vandyne B., Thomas B., Rich J., Bartone S., Beaulieu G., Brown K., Chau T., Christian T., Coker R., Greene D., Haddock T., Jenkins W., Haque G., Marquess M., Pesarchick J., Rethaford R., Stone A., Al Kawas F., Anderson M., Enns R., Sinay I., Mathieu C., Yordanov V., Hramiak I., Haluzik M., Galatius S., Guerci B., Nauck M., Migdalis I., Tan C. B. K., Kocsis G., Giaccari A., Lee M. K., Munoz E. G. C., Cornel J., Birkeland K., Pinto M., Tirador L., Olesinska-Mader M., Shestakova M., Distiller L., Lopez-Sendon J., Eliasson B., Chiang C. -E., Srimahachota S., Mankovsky B., Bethel M. A., Dungan K., Kosiborod M., Alvarisqueta A., Baldovino J., Besada D., Calella P., Cantero M. C., Castano P., Chertkoff A., Cuadrado J., De Loredo L., Dominguez A., Espanol M. V., Finkelstein H., Frechtel G., Fretes J., Garrido Santos N., Gonzalez J., Litvak M., Loureyro J., Maffei L., Maldonado N., Mohr Gasparini D., Orio S., Perez Manghi F., Rodriguez Papini N., Sala J., Schygiel P., Sposetti G., Ulla M., Verra F., Zabalua S., Zaidman C., Crenier L., Debroye C., Duyck F., Scheen A., Van Gaal L., Vercammen C., Damyanova V., Dimitrov S., Kovacheva S., Lozanov L., Margaritov V., Mihaylova-Shumkova R., Nikolaeva A., Stoyanova Z., Akhras R., Beaudry Y., Bedard J., Berlingieri J., Chehayeb R., Cheung S., Conway J., Cusson J., Della Siega A., Dumas R., Dzongowski P., Ferguson M., Gaudet D., Grondin F., Gupta A., Gupta M., Halperin F., Houle P. -A., Jones M., Kouz S., Kovacs C., Landry D., Lonn E., O'Mahony W., Peterson S., Reich D., Rosenbloom A., St-Maurice F., Tugwell B., Vizel S., Woo V., Brychta T., Cech V., Dvorakova E., Edelsberger T., Halciakova K., Krizova J., Lastuvka J., Piperek M., Prymkova V., Raclavska L., Silhova E., Urbanek R., Vrkoc J., Andersen U., Bronnum-Schou J., Hove J., Jensen J. S., Kober L., Kristiansen O. P., Lund P., Melchior T., Nyvad O., Schou M., Boye A., Cadinot D., Gouet D., Henry P., Kessler L., Lalau J. -D., Petit C., Thuan J. -F., Voinot C., Vouillarmet J., Axthelm C., Berger D., Bieler T., Birkenfeld A., Bott J., Busch K., Caca K., Chevts J., Donaubauer T., Erlinger R., Funke K., Grosskopf J., Hagenow A., Hamann M., Hartard M., Heymer P., Huppertz W., Illies G., Jacob S., Jung T., Kahrmann G., Kast P., Kellerer M., Kempe H. -P., Khariouzov A., Klausmann G., Klein C., Kleinecke-Pohl U., Kleinertz K., Koch T., Kosch C., Lorra B., Luedemann J., Luttermann M., Maxeiner S., Milek K., Moelle A., Neumann G., Nischik R., Oehrig-Pohl E., Plassmann G., Pohlmeier L., Proepper F., Regner S., Rieker W., Rose L., Samer H., Sauter J., Schaper F., Schiffer C., Schmidt J., Scholz B. -M., Schulze J., Segner A., Seufert J., Sigal H., Steindorf J., Stockhausen J., Stuebler P., Taeschner H., Tews D., Tschoepe D., Wilhelm K., Zeller-Stefan H., Avramidis I., Bousboulas S., Bristianou M., Dimitriadis G., Elisaf M., Kotsa K., Melidonis A., Mitrakou A., Pagkalos E., Papanas N., Pappas A., Sampanis C., Tentolouris N., Tsapas A., Tzatzagou G., Ozaki R., Hajdu C., Harcsa E., Konyves L., Mucsi J., Pauker Z., Petro G., Ples Z., Revesz K., Sandor V., Vass V., Avogaro A., Boemi M., Bonadonna R., Consoli A., De Cosmo S., Di Bartolo P., Dotta F., Frontoni S., Galetta M., Gambineri A., Gazzaruso C., Giorgino F., Lauro D., Orsi E., Paolisso G., Perriello G., Piatti P., Pontiroli A., Ponzani P., Rivellese A. A., Sesti G., Tonolo G., Trevisan R., Ahn C. W., Baik S. -H., Cha B. -S., Chung C. -H., Jang H. C., Kim C. -J., Kim H. S., Kim I. J., Lee E. Y., Lee H. W., Lee K. -W., Moon K. -W., Namgung J., Park K. S., Yoo S. J., Yu J., Llamas E. -A. B., Cervantes-Escarcega J. -L., Flota-Cervera L. F., Gonzalez-Gonzalez J. G., Pascoe-Gonzalez S., Pelayo-Orozco E. S., Ramirez-Diaz S. -P., Saldana-Mendoza A., Jerjes-Diaz C. S., Torres-Colores J. J., Vidrio-Velazquez M., Villagordoa-Mesa J., Beijerbacht H. P., Groutars R. G. E. J., Hoek B. A., Hoogslag P. A. M., Kooy A., Kragten J. A., Lieverse A. G., Swart H. P., Viergever E. P., Ahlqvist J., Cooper J., Gulseth H., Guttormsen G., Wium C., Arbanil H., Calderon J., Camacho L., Espinoza A. D., Garrido E., Luna A., Manrique H., Revoredo F. M., Gonzales R. V., Rincon L. Z., Zubiate C., Ebo G., Morales-Palomares E., Arciszewska M., Banach M., Bijata-Bronisz R., Derezinski T., Gadzinski W., Gajek J., Klodawska K., Krzyzagorska E., Madej A., Miekus P., Opiela J., Romanczuk P., Siegel A., Skokowska E., Stankiewicz A., Stasinska T., Trznadel-Morawska I., Witek R., Aksentyev S., Bondar I., Demidova I., Dreval A., Ershova O., Galstyan G., Garganeeva A., Izmozherova N., Karetnikova V., Kharakhulakh M., Khokhlov A., Kobalava Z., Koshelskaya O., Kosmacheva E., Kostin V., Koziolova N., Kuzin A., Lesnov V., Lysenko T., Markov V., Mayorov A., Moiseev S., Myasoedova S., Petunina N., Rebrov A., Ruyatkina L., Samoylova J., Sazonova O., Shilkina N., Sokolova N., Vasilevskaya O., Verbovaya N., Vishneva E., Vorobyev S., Vorokhobina N., Zanozina O., Zhdanova E., Zykova T., Burgess L., Coetzee K., Dawood S., Lombard L., Makotoko E., Moodley R., Oosthuysen W., Sarvan M., Calvo Gomez C., Cano Rodriguez I., Castro Conde A., Cequier Fillat A., Cuatrecasas Cambra G., de Alvaro Moreno F., De Teresa Parreno L., Delgado Lista J., Dominguez Escribano J. R., Duran Garcia S., Elvira Gonzalez J., Fernandez Rodriguez J. M., Goday Arno A., Gomez Huelgas R., Gonzalez Juanatey J. R., Hernandez Mijares A., Jimenez Diaz V. A., Jodar Gimeno E., Lucas Morante T., Marazuela M., Martell Claros N., Mauricio Puente D., Mena Ribas E., Merino Torres J. F., Mezquita Raya P., Nubiola Calonge A., Ordonez Sanchez X., Pascual Izuel J. M., Perea Castilla V., Perez Perez A., Perez Soto I., Quesada Charneco M., Quesada Simon A., Redon Mas J., Rego Iraeta A., Rodriguez Alvarez M., Rodriguez Rodriguez I., Saban Ruiz J., Soto Gonzalez A., Tinahones Madueno F., Trescoli Serrano C., Ulied Arminana A., Bachus E., Berndtsson Blom K., Eliasson K., Koskinen P., Larnefeldt H., Lif-Tiberg C., Linderfalk C., Lund G., Lundman P., Moris L., Olsson A., Salmonsson S., Sanmartin Berglund J., Sjoberg F., Soderberg S., Torstensson I., Chen J. -F., Tien K. J., Tseng S. -T., Tu S. -T., Wang C. -Y., Wang J. -H., Phrommintikul A., Yamwong S., Jintapakorn W., Hutayanon P., Sansanayudh N., Bazhan L., Fushtey I., Grachova M., Katerenchuk V., Korpachev V., Kravchun N., Larin O., Mykhalchyshyn G., Myshanych H., Oleksyk O., Orlenko V., Pashkovska N., Pertseva N., Petrosyan O., Smirnov I., Vlasenko M., Zlova T., Aye M., Baksi A., Balasubramani M., Beboso R., Blagden M., Bundy C., Cookson T., Copland A., Emslie-Smith A., Green F., Gunstone A., Issa B., Jackson-Voyzey E., Johnson A., Maclean M., McKnight J., Muzulu S., O'Connell I., Oyesile B., Patterson C., Pearson E., Philip S., Smith P., Sukumaran U., Abbas J., Aggarwala G., Akhter F., Andersen J., Anglade M., Argoud G., Ariani M., Ashdji R., Bakhtari L., Banerjee S., Bartlett A., Baum H., Bays H., Beasley R., Belfort de Aguiar R., Benjamin S., Bhagwat R., Bhargava A., Bode B., Bratcher C., Briskin T., Brockmyre A., Broughton R., Brown J., Budhraja M., Cannon K., Carr J., Cathcart H., Cavale A., Chaykin L., Cheung D., Childress R., Cohen A., Condit J., Cooksey E., Cornett G. M., Dauber I., Davila W., De Armas L., Dean J., Detweiler R., Diaz E., Di Giovanna M., Dor I., Drummond W., Eagerton D., Earl J., Eaton C., Ellison H., Farris N., Fiel T., Firek A., First B., Forgosh L., French W., Gandy W., Garcia R., Gill S., Gordon M., Guice M., Gummadi S., Hackenyos J., Hairston K., Hanson L., Harrison L., Hartman I., Heitner J., Hejeebu S., Hermany P., Hernandez-Cassis C., Hidalgo H., Higgins A., Ibrahim H., Jacobs S., Johnson D., Joshi P., Kaster S., Kellum D., Kim C., Kim E., Kirby W., Knouse A., Kulback S., Kumar M., Kuruvanka T., Labroo A., Lasswell W., Lentz J., Lenzmeier T., Lewis D., Li Z., Lillestol M., Little R., Lorraine R., McKeown-Biagas C., McNeill R., Mehta A., Miller A., Moran J., Morawski E., Nadar V., O'Connor T., Odio A., Parker R., Patel R., Phillips L., Raad G., Rahman A., Raikhel M., Raisinghani A., Rajan R., Rasouli N., Rauzi F., Rohr K., Roseman H., Rovner S., Saba F., Sachson R., Schabauer A., Schneider R., Schuchard T., Sensenbrenner J., Shlesinger Y., Singh N., Sivalingam K., Stonesifer L., Storey D., Suh D., Tahir M., Tan A., Tan M., Taylon A., Thakkar M., Tripathy D., Uwaifo G., Vedere A., Venugopal C., Vo A., Welch M., Welker J., White A., Willis J., Wynne A., Yazdani S., Rosenberg A., Price L., Sigmon K., Lokhngina Y., Xing W., Overton R., Stewart M., Stead J., Lindsay A., Patel V., Ross J., Soffer J., Daga S., Sowell M., Patel P., Garvey L., Ackert J., Abraham S., Sabol M. B., Altobelli D., Ha J., Kulkarni M., Somerville M., Noronha D., Casson E., Zang E., Sandhu C., Kumar R., Chen D., Taft L., Ye J., Shannon J., Wilson T., Babi C., Miller D., Thorpe K., Russell R., Bull G., Hereghty B., Fernandez-Salazar E., Longley T., Donaldson J., Jarosz M., Murphy K., Adams P., James R., Richards J., Sedani S., Althouse D., Watson D., Lorimer J., Lauder S., Schultheis R., Womer T., Wraight E., Li W., Price-Olsen E., Watson A., Kelly A., McLaughlin P., Fleming J., Schubert J., Schleiden D., Harris T., Prakash R., Breneman J., Deshpande S., Saswadkar A., Kumari A., Shitut A., Raorane A., Karmalkar A., Mhambrey A., Bhosale A., Vaphare A., Patil A. P., Khandelwal C., Shaik F., Nadar M., Karka M., Kadgaonkar N., Gupta N., Aher N., Potnis O., Naicker P., Shinde R., Sharma R., Godse R., Solanki S., Sahu S., Dumbre S., Kumar S., Patil S., Mandal T.

المساهمون: Hernandez, Af, Green, Jb, Janmohamed, S, D'Agostino, Rb, Granger, Cb, Jones, Np, Leiter, La, Rosenberg, Ae, Sigmon, Kn, Somerville, Mc, Thorpe, Km, Mcmurray, Jjv, Del Prato, S, Califf, Rm, Holman, R, Demets, D, Riddle, M, Goodman, S, Mcguire, D, Alexander, K, Devore, A, Melloni, C, Patel, C, Kong, D, Bloomfield, G, Roe, M, Tricoci, P, Harrison, R, Lopes, R, Mathews, R, Mehta, R, Schuyler Jones, W, Vemulapalli, S, Povsic, T, Eapen, Z, Dombrowski, K, Kolls, B, Jordan, D, Ambrosy, A, Greene, S, Mandawat, A, Shavadia, J, Cooper, L, Sharma, A, Guimaraes, P, Friedman, D, Wilson, M, Endsley, P, Gentry, T, Collier, J, Perez, K, James, K, Roush, J, Pope, C, Howell, C, Johnson, M, Bailey, M, Cole, J, Akers, T, Vandyne, B, Thomas, B, Rich, J, Bartone, S, Beaulieu, G, Brown, K, Chau, T, Christian, T, Coker, R, Greene, D, Haddock, T, Jenkins, W, Haque, G, Marquess, M, Pesarchick, J, Rethaford, R, Stone, A, Al Kawas, F, Anderson, M, Enns, R, Sinay, I, Mathieu, C, Yordanov, V, Hramiak, I, Haluzik, M, Galatius, S, Guerci, B, Nauck, M, Migdalis, I, Tan, Cbk, Kocsis, G, Giaccari, A, Lee, Mk, Munoz, Egc

مصطلحات موضوعية: Adult, Aged, Cardiovascular Disease, Diabetes Mellitus, Type 2, Double-Blind Method, Drug Administration Schedule, Female, Glucagon-Like Peptide 1, Human, Hypoglycemic Agent, Injections, Subcutaneou, Kaplan-Meier Estimate, Male, Middle Aged, Myocardial Infarction, Stroke, Treatment Outcome, Settore MED/13 - ENDOCRINOLOGIA

الوصف: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/30291013; info:eu-repo/semantics/altIdentifier/wos/WOS:000448414700030; volume:392; issue:10157; firstpage:1519; lastpage:1529; numberofpages:11; journal:THE LANCET; http://hdl.handle.net/2108/211304Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85055101508

الإتاحة: https://doi.org/10.1016/S0140-6736Test(18)32261-X
http://hdl.handle.net/2108/211304Test

المؤلفون: Mann JFE, Ørsted DD, Brown-Frandsen K, Marso SP, Poulter NR, Rasmussen S, Tornøe K, Zinman B, Buse JB, LEADER Steering Committee and Investigators. Bergenstal R, Daniels G, Moses AC, Nauck M, Nissen S, Pocock S, Steinberg W, Stockner M, Kristensen P, Ravn LS, Zychma M, Flyvbjerg A, Ford I, Kloos RT, Schactman MJ, Sleight P, Swedberg K, Tenner SM, Akalın S, Arechavaleta R, Bain S, Babkowski MC, Benroubi M, Berard L, Comlekci A, Czupryniak L, Eliasson B, Eriksson M, Fonseca V, Franek E, Gross J, Hafidh K, Haluzik M, Hayes F, Huang YY, Jacob S, Kaddaha G, Khalil A, Kilhovd B, Laakso M, Leiter L, Lalic N, Ji L, Luedemann J, Mannucci E, Marre M, Masmiquel L, Mota M, Omar M, O’Shea D, Pan C, Petrie J, Pieber T, Pratley R, Raz I, Rea R, Rutten G, Satman I, Shestakova M, Simpson R, Smith D, Tack C, Tarnow L, Thomas N, Van Gaal L, Travert F, Vidal J, Warren M, Yoon KH, Tuttle RM, Sheerman SI, Hegedüs L, Baerwald H, Bergenstal M, Celik S, Dias C, Eder M, Fitzgibbons S, Irvhage L, Kloluckova J, Kriulianski R, McDuffie R, Moen S, Paster A, Saalfeld RM, Sankar K, Shehaj E, Swierzewska P, Tiktin M, Tovey S, Gibson CM, Chakrabarti AK, Dashe JF, 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Alves J, Araujo L, Arruda V, Augusto GA, Baggentoss R, Balestrassi L, Barbosa M, Barcelos I, Belem L, de Bem A, Betti RT, Bona R, Bosco A, Branda J, Bronstein M, Bueno T, Bulcão T, Caiado F, Camazzola F, Cambréa MF, Campos S, Canani L, Carra MK, Caruso S, Carvalho N, Casillo A, Castro D, Cavalcanti T, Cavichioli V, Cercato C, Chacra A, Challela W, Charchar HS, Chaves C, Chrisman C, Correia-Deur J, da Costa A Jr, Costa M, Costi B, Coutinho P, Coutinho W, Cunha MR, Daher J Jr, Davini E, Democh D Jr, Eliaschewitz F, Esmanhoto Facin G, Farias F, Felício J, Fernandes V, Filho CS, Filho FF, Filho M, Fontan D, Fontenele AP, Forti A, Franco D, Freire K, Fusaro A, Genestreti P, Gerchman F, Godi A, Gomes KF, Gonçalves P, Gonçalves R, Griz L, Grossman M, Gurgel MH, Vasconcellos Haddad AW, Halpern A, Hissa M, Inuy A, Jaime J, Jonasson T, Jorge JC, Malucelli FJ, Kohara S, Kramer C, Lacerda C, Ladeira S, Lana J, Lastebasse F, Leitão A, Leite S, Lerário AC, Lima D, Lima M, Lippi V, Lunardi M, Machado E, Maia F, Maia J, Maia KP, Mañas N, Marchisotti F, Marinho C, Martins C, Figueiredo de Medeiros F, Melo A, Melo F, Mendonca E, Mendonça P, Filho RM, Miguel M, Miléo K, Miyahara M, Montenegro AP, Moraes A, Moreira A, Ítalo Mota J, Mothe FS, Murro A, Nakatani V, Napoli TF, Neto BG, Neto OQ, Niclewicz E, Ohe LN, Oliveira F, Oliveira M, Panarotto D, Parente E, Parolin S, Pechmann L, Costa da Penha P, Perlamagna L, Perotta B, Pimentel L, Pinto M, Poço C, Ponte C, Prazeres P, Quintao E, Raduan R, Rassi DT, Rassi N, Reck L, Montenegro R Jr, Ribeiro R, Rodovalho S, Silveira Rodrigues G, Rollin G, Rossi S, Sabino C, Sales AP, Salles J, Sampaio CR, Santana L, Sato V, da Silva Santos M, Santos NL, Santos R, Saraiva J, Sartori C, Sena R, Sevilha M, Sgarbi J, Silva D, D'albuquerque Silva L, Silva ME, Siqueira K, Soares S, Sobreira W, Sousa B, Souza AC, Souza B, Tambascia M, Tarantino R, Tenor F, Tomarchio M, Triches C, Tristão LJ, Valenti A, Vasques E, Vencio S, Vianna A, Munhoz Vidotto T, Vieira S, Villar H, Visconti G, Volaco A, Wajchenberg B, Zanatta L, Zimmerman L, Abbott EC, Abu-Bakare A, Advani A, Allison R, Bishara P, Bowering CK, Cheng A, Chouinard S, Clayton D, Conway J, D'Amours M, de Tugwell B, DeYoung P, D'Ignazio G, Dube F, Ekoe JM, Fagan S, Garceau C, Gottesman I, Hanna A, Harris S, Hramiak IM, Hurd C, Imran S, Josse R, Joyce C, Kaiser S, Khan F, Kirouac I, Kovacs C, Labonte I, Langlois WJ, Levac MF, Liutkus J, McDonald C, Milosevic V, Nyomba BL, Paul T, Raby K, Ransom T, Reichert SM, Retnakaran R, Rabasa-Lhoret R, Raff E, Shaikholeslami R, Sigalas J, Yip CE, Weisnagel SJ, Woo V, Bao Y, Cai X, Chen J, Chen K, Chen M, Chen X, Chen Y, Ji Y, Lei J, Li H, Liu P, Mu Y, Ren M, Ren Y, Shi Y, Wang D, Wang F, Wang J, Wang Y, Yan L, Yang G, Yang J, Yu X, Yuan G, Xu M, Zhao X, Zheng J, Zhou L, Anderlová K, Brožová J, Haluzík M, Hanušová V, Kosák M, Křížová J, Mráz M, Owen K, Rušavý Z, Tomešová J, Trachta P, Žourek M, Andersen PH, Boesgaard T, Christensen S, Gram J, Gregersen S, Henriksen JE, Hermansen K, Jakobsen PE, Jensen J, Krogsaa A, Larsen M, Lervang HH, Madsbad S, Mortensen L, Olesen T, Pietraszek A, Ridderstråle M, Safai N, Schioldan AG, Schmidt C, Snorgaard O, Stidsen J, Cederberg H, Haapamäki H, Hukkanen J, Jauhiainen R, Kujari ML, Lahtela J, Laine M, Mäkelä J, Miilunpohja M, Savolainen M, Taurio J, Vänttinen M, Creton C, Cosma NV, Dillinger J, Jacques JL, Guedj AM, Moulla M, Petit C, Ratsianoharana V, Richter D, Rodier M, Roussel R, Hinz A, Politz E, Esser M, Deuse U, Mittag D, Hagenow A, Jacob F, Jordan R, Gantke D, Venschott-Jordan U, Löhr C, Klausmann G, Eschenbrücher K, Karakas M, Jahrsdörfer B, Kunze MR, Wöhrle J, König W, Spielhagen H, Kilimnik A, Lüdemann HP, Lüdemann J, Mölle A, Mölle M, Müller J, Appelt S, Sauter A, Sauter J, Hartmann U, Löw A, Krötz F, Sohn HY, von Schacky C, Klauss V, Braun D, Segner A, Degtyareva E, Kreutzmann K, Paschmionka R, Hauck N, Sihal O, Busch AK, Maus O, Stübler P, Füllgraf-Horst S, Vietzke A, Müller C, Tosch-Sisting R, Lengsfeld B, Thaler J, Schaum T, Steindorf J, Steindorf S, König A, Reitschuster S, Schlott D, Clever HU, Witzel P, Kempe HP, Stemler L, Benis A, Diakoumopoulou E, Kazakos K, Kypraios N, Liatis S, Pagkalos E, Siami E, Tentolouris N, Alur VC, Agrawal M, Ali M, Asirvatham A, Asirvatham E, Bandgar TR, Balaji M, Bardoloi N, Baruah M, Bekur R, Bhansali A, Bhatia S, Bhonsley S, Bhuyan S, Borah B, Bright N, Ambrish C, Chaudhury T, Choudhury S, Chellan G, Das M, Dharmalingam M, Dutta P, Erugu A, Vinutha FP, Gunasekaran P, Das Gupta R, Iqbal A, Jagadish P, Jain S, Jebasingh H, John A, John M, Kalra S, Kasaragod P, Kesavadev J, Kumar H, Kumar P, Lakshmanan V, Lila AR, Mathew T, Miyen H, Mohan T, Motha A, Murthy C, Shivashankara N, Nanaiah A, Ommen T, Pani K, Pandey K, Paramesh S, Paramesh V, Pillai B, Prabhu M, Kalki RC, Ramachandran S, Ramu M, Rao Y, Reddy S, Saikia P, Saravu K, Selvam K, Sethi B, Shankar A, Sharma A, Shah N, Shankar P, Shetty R, Shivane V, Srivalli S, Thaseen S, Sarada S, Shirisha A, Subramani M, Balaji V, Mohan V, Padmanaban V, Verma M, Vidyasagar S, Walinjkar V, Walia R, Davenport C, Forde H, Gadintshware G, Gan KJ, Khattak A, O'Connell J, O'Shea D, Beilin V, Cahn A, Cohen O, Cukierman-Yaffe T, Daoud D, Darawsha M, Dicker D, Gavish A, Hochberg I, Ilany J, Inbal U, Itzhak B, Karasik A, Karnieli E, Khader N, Khamaisi M, Lender D, Lieberman GS, Mahamid R, Marcoviciu D, Michael L, Minuchin O, Mosenzon O, Narevichius F, Percik R, Potekhin M, Sabbah M, Sawaed S, Schurr D, Segal E, Slezak L, Vollach I, Zaina A, Zloczower M, Zolotov S, Antenore A, Arnone M, Arturi F, Barbaro V, Barone M, Di Biagio R, Buscemi C, Buscemi S, Buzzetti R, Di Carlo A, Carlone A, Caruso V, Casadidio I, Cerrelli F, Ciavarella A, Cipolloni L, Colella A, Colotto M, Consoli A, Crippa VG, Cuccuru I, Cufone S, Desideri C, Fallarino M, Febo F, Filetti S, Foffi C, Formoso G, Frosio L, Di Fulvio P, Gambineri A, Ginestra F, Grimaldi MS, Lamanna C, Leto G, Lucotti P, Lugarà M, 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J, Cardenas C, Carlton J, Carpio G, Carrol A, Cartwright L, Casanova G, Castaneda L, Castle M, Castro L, Catangay J, Chaidarun S, Chambers J, Chambliss T, Chandra L, Chang A, Chang S, Chappel J, Chappel C, Chappell T, Charles C, Chavira A, Chaykin L, Check E, Chee L, Cherry A, Chestnut A, Chiarot J, Chiniwala N, Chionh K, Choe J, Christiansen M, Chrzanowski S, Chuang E, Chuck L, Clyatt J, Cohan B, Cohen R, Comi R, Comulada-Rivera A, Conner K, Connor G, Contreras R, Cook K, Cook R, Corder C, Cornejo B Sr, Cornette L, Cortes G, Cortez L, Cox C, Cox G, Craig W, Cramer B, Cromer C, Cromer M, Cuddihy R, Culmer D, Curran H, Curran M, Dadis C, Dagogo-Jack S, Dairywala I, D'Alessio D, Damberg G, Dang A, Daniel K, Davidson M, Dean J, DeBold R, Deitz P, Del M, Delaney D, Delgado E, DeMicco M, DeMuro MA, DeSalle D, Desouza C, Devireddy K, DeVries B, Dezube M, Diab I, Diesburg-Stanwood A, Dilliard J, Dilling J, Diner J, Dishongh K, Dodis R, Doing C, Doll W, Donoho A, Donovan D, Doremus N, Dorfman S, Doshi P, Dostou J, Douglas D, Douglass S, Dowell M, Drazich E, Driver E, Du H, DuBose R III, Duclos M, Dunn K, Dunnam T, Durham N, Dye L, Eagerton D, Ebenibo S, Edeoga C, Edwards G, Ekwensi J, El Asmar I, El Sayad N, Eliopoulos C, Elkosseifi M, Elmer R, Elmore M, Elson D, ElZein L, Emmert L, Erbe L, Estes S, Estrada L, Estrada A, Eveleigh T, Everhart B, Faas F, Faircloth C, Farmer M, Fehr K, Ferguson T, Fernandes J, Ferree K, Ferrington B, Fitzhugh M, Fitzsimmons R, Flanders D, Flores M, Flores E, Flores J, Florida C, Flynn J, Folmar P, Forbes R, Ford W, Fowler M, Fraker A, Francis S, Franco-Cotto E, Fratila C, Fuentes M, Galagan R, Galloway A, Garcia M, Garcia R, Garriott M, Garza J, Gass N, Gates S, Geary M, Geiger K, Geishauser J, Giglio A, Gilbert M, Godwin S, Goetter B, Goley A, Golici L, Gomori E, Gonzales J, Gore A, Gorman T, Gosmanova A, Goswami K, Gotham A, Govoni J, Graddick S, Grant T, Greca A, Green C, Greenbaum K, Greenwald J, Grover D, Grunberger G, Guice M, Guirao D, Gunna V, Guseva N, Ha T, Hagan A, Hager S, Haggag A, Haggar M, Hamilton M, Hamlet P, Hammond J, Hansen A, Harrell W, Harris E, Harris K, Harris M, Harrison L, Hartman I, Hatch A, Hayes D, Hayes M, Heath J, Heineman R, Heinzman A, Hendrick M, Herbst R, Hermayer K, Hibbard J, Hill WD, Hilliard B, Hix M, Hoch B, Hollander P, Holmes Z, Horobetz C, Horowitz R, Hsieh P, Hsieh S, Htun W, Huang J, Huber C, Hudson T, Huizar S, Hull B, Hull J, Hummer K, Hundal R, Hunt G, Hunt V, Hutchinson P, Hwang J, Iannamorelli A, Iannuzzi L, Ingram M, Iram N, Ismail-Beigi F, Jabbour S, Jackson T, Jaen L, Jain V, Jannesari R, Januski V, Japa U, Jarvis K, Jayson L, Jensen R, Jester D, Jocko C, Johnson C, Johnson M, Johnston K, Jones D, Jones J, Jordan T, Juarez M, Kaapuraala A, Kain A, Kaiser V, Kamradt K, Karatoprakli P, Karegar M, Karounos C, Karounos D, Karunaratne H, Katalenich B, Katic K, Katz M, Kaur G, Kawa A, Keib C, Keider G, Kem D, Kennedy R, Kenney B, Kereiakes D, Ketana M, Kettinger L, Khaira A, Khan A, Khan K, Khan M, Khoo T, Khrlobyan N, Kilgore J, Kim G, Kimble S, Kinsley M, Kitchen T, Klick M, Kniffen W, Knight R, Kodzwa D, Koenig T, Komarovskiy K, Kong Y, Koontz D, Krishnasamy S, Krueger E, Kuechenmeister L, Kuehl A, Kuettel K, Kugler D, Kulow T, Kupriyanchik I, Kuruvanka T, Kushner D, Kwon E, Kwon S, Kyle M, LaBryer L, Labuda J, Lafave J, Laguerre J, Laliberte A, Lane J, Langel C, Lann D, Largay J, Latif K, Latus T, Lawrence J, Ledger G, Lee FG, Lee E, Leffert J, Leinung M, Lenhard MJ, Lentino J, Leon J, Leonard M, Letassy N, Leuck K, Levin P, Levinson D, Lewis M, Light T, Lim J, Lindamood R, Lingvay I, Lipps J, Lisa A, Livingston Y, Llamas L, Loesch R, Long T, Looby R, Lopez C, Lorenz T, Lovre D, Lu P, Lucas K, Luevano G, Luidens M, Luna B, Luttrell L, Lyons T, MacAdams M, Mack D, Mack M, Madden M, Madder R, Madireddy S, Mae L, Mahakala A, Maheshwari H, Malbari H, Maldonado N, Mallitz M, Mandviwala M, Mann K, Mardahay M, Marino J, Marney A, Marshall L, Martin A, Martin E, Martinez G, Martinez-Miss S, Marx P, Massara L, Mastoor M, Matfin G, Maturu A, Maurides P, May M, Mayfield R, Maynard B, Mazza A, McCann K, McCoy J, McCoy T, McCullen MK, McDaniel C, McDaniel AM, McDermott M, McDonald A, McMasters B, McMurray C, Medlin T, Meinel M, Mendez I, Menefee J, Meredith M, Merriweather M, Mersey J, Messino C, Meyer S, Meyers L, Michael D, Midyett C, Miklius A, Milford E, Miller B, Miller H, Milligan M, Minor A, Miranda-Palma B, Mirarchi N, Mittadodla S, Mittle J, Moffat A, Mohaupt S, Mohiuddin K, Mokshagundam S, Monaco S, Monsaert R, Montano-Pereira C, Montgomery A, Moody K, Moon M, Moore D, Moore L, Morawski E, Moreau C, Morin D, Moscoa C, Motzkin C, Mueller R, Munoz C, Munoz M, Myneni A, Naderi B, Nagireddy P, Naidu J, Naidu R, Naik S, Naimark R, Nardicchi M, Ndukwu I, Neller C, Netten-Foster L, Neumiller J, New T, Newman S, Newton T, Nguyen B, Nicol B, Nicol P, Ninivaggi L, Niswender K, Norman L, Noworatzky G, Nyenwe E, O'Brien H, O'Connell T, Oden W, Odugbesan A, Oliver M, Oliver T, Olmeda C, O'Neil C, Oremus R, Ortega T, Ortiz-Santos S, Osborn T, Padmanabhan S, Papacostea O, Park I, Parker A, Parker K, Parker R, Patel C, Patel M, Patel R, Patino M, Patterson S, Paulson K, Paz A, Pemba R, Pepe C, Perez J, Perez T, Perry D, Phillips B, Phillips J, Pickett A, Pinson M, Pitzer R, Poduri M, Poehls J, Poteat T, Powell L, Prasad S, Prevost J, Price E, Priest D, Prieto L, Purewal T, Purighalla R, Purighalla U, Quadrel M, Qureshi A, Radhamma R, Rafla E, Rajab H, Ramalingam R, Ramirez A, Ramirez J, Ramirez K, Ramirez M, Randall M, Rangaraj U, Rao V, Rasmussen P, Rasouli N, Ray A, Reed J, Rems L, Renaud K, Reno M, Resnick M, Reusch J, Reynolds L, Rhoton K, Rhudy J, Ricci C, Rice L, Richardson A, Richardson L, Rickard H, Rickels M, Riff D, Rightenour N, Risser J, Rizvi A, Robertson J, Robinson A, Robinson R, Rockwell M, Rodriguez JP, Rodriguez M, Rojas M, Rojas W, Rooker-Morris L, Root C, Rose M, Rosenberg R, Rosenstock J, Roth M, Ruby R, Sachson R, Sack P, Sadler RK, Sahai S, Salazar J, Salgam M, Samal A, Samson A, Sanagorski R, Sanchez A, Sandberg J, Sanderson M, Sandoval J, Santiago E, Sapp T, Saunders J, Schill J, Schott C, Schreiman R, Schu D, Schuh K, Schutta M, Schwartz J, Schweppe L, Scofield H, Scribner A, Seal J, Sealock J, Seaton B, Sedlak-Hanslik T, Seekins K, Segal M, Seggelke S, Semenza S, Sentman P, Serra M, Seshadri P, Sevilla E, Shah S, Shaheen K, Shanik M, Shaw J, Sheets M, Shellabarger C, Sher J, Shippey J, Shivaswamy V, Shomali M, Shore D, Shroff P, Siddiqui T, Siegwald A, Silver R, Simmons D, Simons R, Sinan A, Singh M, Sirinvaravong S, Skero J, Slover-Zipf J, Small S, Smith B, Smith K, Smith M, Sohl J, Solarz SH, Soler D, Sood A, Sora N, Souchet A, Soule J, Sparks J, Spector L, Speicher R, Spillers L, Spivey T, Springer N, Sprouse H, St John J, Stacey A, Stacey H, Stafford M, Stagner E, Staples K, Steadman E, Steed R, Steeves G, Steinberg H, Stell C, Stirman E, Straub K, Strock E, Sue M, Suris O, Sutton T, Tabbah I, Talsania M, Tang R, Tapia J, Taylor K, Taylor-Hancher R, Teator R, Tekateka M, Temple B, Temple K, Teodori M, Tharp P, Thethi T, Theuma P, Thomas S, Thottan A, Thrasher J, Thrasher L, Tiemeyer M, Tinney I, Tobin T, Toma S, Tovar M, Townsend J, Trantow C, Traylor H, Trevino M, Troy M, Trumper D, Tryggestad J, Tucker C, Turner J, Turney R, Tuten C, Tyzack J, Ullo L, Underkofler C, Unger J, Urdanetta R, Valdivia V, Valenti S, Vanderheiden A, Vanderlinde-Wood M, Varma C, Vasquez E, Vazquez M, Vickery D, Villafuerte B, Villegas C, Vivar J, Vivekananthan K, Vo G, Vukojicic K, Wachter A, Wahl D, Waitmann J, Walker D, Walsh J, Walsh K, Walton A, Wang A, Wardell K, Watkins S, Watkinson J, Watts M, Watwe V, Weaver N, Weber R, Wedick C, Weeks D, Weeks L, Weindorff K, Weinstein R, Weiss S, Wenger K, Wentworth M, Werner A, West M, Whelan S, White B, White J, Whitmire M, Whittington R, Wical J, Wigley C, Wilkins F, Will K, Williams A, Wilson LE, Wince M, Wine S, Winkle P, Winner C, Wise J, Witte M, Wittenmyer J, Wood C, Wood R, Woodruff C, Worthington B, Wynn D, Wysham C, Xavier P, Yela S, Yenoby L, Young L, Younus N, Yourell V, Zaid M, Zubair I.

المساهمون: Mann, Jfe, Ørsted, Dd, Brown-Frandsen, K, Marso, Sp, Poulter, Nr, Rasmussen, S, Tornøe, K, Zinman, B, Buse, Jb, Bergenstal R, LEADER Steering Committee and Investigators., Daniels, G, Moses, Ac, Nauck, M, Nissen, S, Pocock, S, Steinberg, W, Stockner, M, Kristensen, P, Ravn, L, Zychma, M, Flyvbjerg, A, Ford, I, Kloos, Rt, Schactman, Mj, Sleight, P, Swedberg, K, Tenner, Sm, Akalın, S, Arechavaleta, R, Bain, S, Babkowski, Mc, Benroubi, M, Berard, L, Comlekci, A, Czupryniak, L, Eliasson, B, Eriksson, M, Fonseca, V, Franek, E, Gross, J, Hafidh, K, Haluzik, M, Hayes, F, Huang, Yy, Jacob, S, Kaddaha, G, Khalil, A, Kilhovd, B, Laakso, M, Leiter, L, Lalic, N, Ji, L, Luedemann, J, Mannucci, E, Marre, M, Masmiquel, L, Mota, M, Omar, M, O’Shea, D, Pan, C, Petrie, J, Pieber, T, Pratley, R, Raz, I, Rea, R, Rutten, G, Satman, I, Shestakova, M, Simpson, R, Smith, D, Tack, C, Tarnow, L, Thomas, N, Van Gaal, L, Travert, F, Vidal, J, Warren, M, Yoon, Kh, Tuttle, Rm, Sheerman, Si, Hegedüs, L, Baerwald, H, Bergenstal, M, Celik, S, Dias, C, Eder, M, Fitzgibbons, S, Irvhage, L, Kloluckova, J, Kriulianski, R, Mcduffie, R, Moen, S, Paster, A, Saalfeld, Rm, Sankar, K, Shehaj, E, Swierzewska, P, Tiktin, M, Tovey, S, Gibson, Cm

مصطلحات موضوعية: liraglutide, randomized controlled trial, type 2 diabetes, renal outcomes

الوصف: BACKGROUND: In a randomized, controlled trial that compared liraglutide, a glucagon-like peptide 1 analogue, with placebo in patients with type 2 diabetes and high cardiovascular risk who were receiving usual care, we found that liraglutide resulted in lower risks of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) and death. However, the long-term effects of liraglutide on renal outcomes in patients with type 2 diabetes are unknown. METHODS: We report the prespecified secondary renal outcomes of that randomized, controlled trial in which patients were assigned to receive liraglutide or placebo. The secondary renal outcome was a composite of new-onset persistent macroalbuminuria, persistent doubling of the serum creatinine level, end-stage renal disease, or death due to renal disease. The risk of renal outcomes was determined with the use of time-to-event analyses with an intention-to-treat approach. Changes in the estimated glomerular filtration rate and albuminuria were also analyzed. RESULTS: A total of 9340 patients underwent randomization, and the median follow-up of the patients was 3.84 years. The renal outcome occurred in fewer participants in the liraglutide group than in the placebo group (268 of 4668 patients vs. 337 of 4672; hazard ratio, 0.78; 95% confidence interval [CI], 0.67 to 0.92; P=0.003). This result was driven primarily by the new onset of persistent macroalbuminuria, which occurred in fewer participants in the liraglutide group than in the placebo group (161 vs. 215 patients; hazard ratio, 0.74; 95% CI, 0.60 to 0.91; P=0.004). The rates of renal adverse events were similar in the liraglutide group and the placebo group (15.1 events and 16.5 events per 1000 patient-years), including the rate of acute kidney injury (7.1 and 6.2 events per 1000 patient-years, respectively). CONCLUSIONS: This prespecified secondary analysis shows that, when added to usual care, liraglutide resulted in lower rates of the development and progression of ...

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/28854085; info:eu-repo/semantics/altIdentifier/wos/WOS:000408626400007; volume:377; issue:9; firstpage:839; lastpage:848; numberofpages:10; journal:NEW ENGLAND JOURNAL OF MEDICINE; http://hdl.handle.net/11585/619768Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85028547742

الإتاحة: https://doi.org/10.1056/NEJMoa1616011Test
http://hdl.handle.net/11585/619768Test

المؤلفون: Pi Sunyer, X., Astrup, A., Fujioka, K., Greenway, F., Halpern, A., Krempf, M., Lau, D., le Roux, C., Violante Ortiz, R., Jensen, C., Wilding, J. COLLABORATORS: amann A, Barakat A, Blüher M, Linn T, Mölle A, Segner A, Stübler P, Tosch Sisting R, Pacini F, Santini F, Marchesini G, Rotella CM, Invitti C, Vettor R, Raya PM, Freijoo FC, de Barbará RG, Carraro R, Bobillo ER, de la Cuesta C, Farsang C, Csaszar A, Zahorska Markiewicz B, Pupek Musialik D, Franek E, Ostrowska L, Olszanecka Glinianowicz M, Lalic N, Micic D, Ludvik B, Paulweber B, Prager R, Scheen A, Van Gaal L, Astrup AV, Hermansen K, Madsbad S, Rissanen A, Nieminen S, Savolainen M, Krempf M, Romon M, Laville M, Marre M, Mira R, Finucane F, Veenendaal A, van Berkum F, Johannsson Vidarsdóttir S, Van de Walle V, Meesters E, Hjelmesæth J, Klemsdal TO, Kulseng B, Bach Kliegel B, Laederach K, Villiger L, Golay A, Bilz S, Sathyapalan T, Bain S, Kumar S, Le Roux CW, Lean ME, McGowan B, Rehman T, Wilding J, Wittert G, Caterson I, Proietto J, Prins J, Geloneze Neto B, Gross JL, Chacra AR, Halpern A, Suplicy Hde A, Chow FC, Thacker HP, Chadha M, Chandalia H, Unnikrishnan A, Kalra S, Deshpande N, Shunmugavelu M, Deshmukh VC, Maislos M, Lieberman GS, Shimon I, Stern N, Nabriski D, Karnieli E, Shehadeh N, Gonzalez Galvez G, Arechavaleta Granell Mdel R, Violante Ortiz RM, Franco GM, Gurieva I, Suplotova LA, Troshina E, Ruyatkina LA, Voychik EA, Martsevich S, Startseva MA, Seeber ME, Badat A, Ellis G, Altuntas Y, Guler S, Ulgen E, Delibasi T, Chetty T, Hart R, Janzen J, Labonte I, Lau D, Liutkus J, O'Keefe D, Padwal R, Ransom TP, Tytus R, Weisnagel SJ, Adler J, Aqua K, Aronoff SL, Bedel GW, Blevins TC, Blumenau J, Brockmyre AP, Call RS, Canadas R, Chaykin LB, Cohen K, Conrow JK, Davis MG, Downey HJ, Drosman SR, Duckor S, Farmer H, Farrell J, Fehnel S, Finneran MP, Forbes R, Forker A, Fredrick M, Fujioka K, Geller SA, Gill S, Glaser L, Greco SN, Greenway FL, Harper W, Herman L, Hoekstra J, Ingebretsen R, Ison R, Jain RK, Kaplan R, Kaster SR, Haase GA, Kerzner B, Kirstein JL, Koltun W, Krieger DR, Lewis CE, Madder R, Marple RN, McDermott EJ, Mello CJ, Miller AB, Mullen J, Nardandrea J, O'Neil P, Pi Sunyer F, Pucillo RM, Rhee C, Redrick S, Pardini A, Rothman J, Rubino DM, Sellers G, Smith T, Byars WD, Soufer J, Sussman AM, Patrick K, Schramm EL, Van Cleeff M, Berg SR, Wyatt HR, Simon J.A., BUSCEMI, Silvio

المساهمون: Pi-Sunyer, X., Astrup, A., Fujioka, K., Greenway, F., Halpern, A., Krempf, M., Lau, D., le Roux, C., Violante Ortiz, R., Jensen, C., Wilding, J. COLLABORATORS: amann A, Barakat A, Blüher M, Linn T, Mölle A, Segner A, Stübler P, Tosch-Sisting R, Pacini F, Santini F, Marchesini G, Rotella CM, Invitti C, Vettor R, Buscemi S, Raya PM, Freijoo FC, de Barbará RG, Carraro R, Bobillo ER, de la Cuesta C, Farsang C, Csaszar A, Zahorska-Markiewicz B, Pupek-Musialik D, Franek E, Ostrowska L, Olszanecka-Glinianowicz M, Lalic N, Micic D, Ludvik B, Paulweber B, Prager R, Scheen A, Van Gaal L, Astrup AV, Hermansen K, Madsbad S, Rissanen A, Nieminen S, Savolainen M, Krempf M, Romon M, Laville M, Marre M, Mira R, Finucane F, Veenendaal A, van Berkum F, Johannsson-Vidarsdóttir S, Van de Walle V, Meesters E, Hjelmesæth J, Klemsdal TO, Kulseng B, Bach-Kliegel B, Laederach K, Villiger L, Golay A, Bilz S, Sathyapalan T, Bain S, Kumar S, Le Roux CW, Lean ME, McGowan B, Rehman T, Wilding J, Wittert G, Caterson I, Proietto J, Prins J, Geloneze Neto B, Gross JL, Chacra AR, Halpern A, Suplicy Hde A, Chow FC, Thacker HP, Chadha M, Chandalia H, Unnikrishnan A, Kalra S, Deshpande N, Shunmugavelu M, Deshmukh VC, Maislos M, Lieberman GS, Shimon I, Stern N, Nabriski D, Karnieli E, Shehadeh N, Gonzalez-Galvez G, Arechavaleta-Granell Mdel R, Violante Ortiz RM, Franco GM, Gurieva I, Suplotova LA, Troshina E, Ruyatkina LA, Voychik EA, Martsevich S, Startseva MA, Seeber ME, Badat A, Ellis G, Altuntas Y, Guler S, Ulgen E, Delibasi T, Chetty T, Hart R, Janzen J, Labonte I, Lau D, Liutkus J, O'Keefe D, Padwal R, Ransom TP, Tytus R, Weisnagel SJ, Adler J, Aqua K, Aronoff SL, Bedel GW, Blevins TC, Blumenau J, Brockmyre AP, Call RS, Canadas R, Chaykin LB, Cohen K, Conrow JK, Davis MG, Downey HJ, Drosman SR, Duckor S, Farmer H, Farrell J, Fehnel S, Finneran MP, Forbes R, Forker A, Fredrick M, Fujioka K, Geller SA, Gill S, Glaser L, Greco SN, Greenway FL, Harper W, Herman L, Hoekstra J, Ingebretsen R, Ison R, Jain RK, Kaplan R, Kaster SR, Haase GA, Kerzner B, Kirstein JL, Koltun W, Krieger DR, Lewis CE, Madder R, Marple RN, McDermott EJ, Mello CJ, Miller AB, Mullen J, Nardandrea J, O'Neil P, Pi-Sunyer F, Pucillo RM, Rhee C, Redrick S, Pardini A, Rothman J, Rubino DM, Sellers G, Smith T, Byars WD, Soufer J, Sussman AM, Patrick K, Schramm EL, Van Cleeff M, Berg SR, Wyatt HR, Simon JA.

مصطلحات موضوعية: Adult, Blood Glucose, Body Mass Index, Combined Modality Therapy, Counseling, Diarrhea, Diet, Reducing, Double-Blind Method, Exercise, Female, Glucagon-Like Peptide 1, Human, Hypoglycemic Agent, Injections, Subcutaneou, Male, Middle Aged, Nausea, Obesity, Weight Loss

الوصف: BACKGROUND: Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagon-like peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously. METHODS: We conducted a 56-week, double-blind trial involving 3731 patients who did not have type 2 diabetes and who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension. We randomly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were the change in body weight and the proportions of patients losing at least 5% and more than 10% of their initial body weight. RESULTS: At baseline, the mean (±SD) age of the patients was 45.1±12.0 years, the mean weight was 106.2±21.4 kg, and the mean BMI was 38.3±6.4; a total of 78.5% of the patients were women and 61.2% had prediabetes. At week 56, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of -5.6 kg; 95% confidence interval, -6.0 to -5.1; P<0.001, with last-observation-carried-forward imputation). A total of 63.2% of the patients in the liraglutide group as compared with 27.1% in the placebo group lost at least 5% of their body weight (P<0.001), and 33.1% and 10.6%, respectively, lost more than 10% of their body weight (P<0.001). The most frequently reported adverse events with liraglutide were mild or moderate nausea and diarrhea. Serious events occurred in 6.2% of the patients in the liraglutide group and in 5.0% of the patients in the placebo group. CONCLUSIONS: In this study, 3.0 mg of liraglutide, as an ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/26132939; info:eu-repo/semantics/altIdentifier/wos/WOS:000357218700004; volume:373; issue:1; firstpage:11-22; lastpage:22; numberofpages:11; journal:NEW ENGLAND JOURNAL OF MEDICINE; http://hdl.handle.net/10447/140072Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84936166069

الإتاحة: https://doi.org/10.1056/NEJMoa1411892Test
http://hdl.handle.net/10447/140072Test

المؤلفون: Stuebler, Antonia G., Jansen, Michaela

المصدر: Biophysical Journal; December 2020, Vol. 119 Issue: 12 p2593-2603, 11p

مستخلص: The intracellular domain of the serotonin type 3A receptor, a pentameric ligand-gated ion channel, is crucial for regulating conductance. Ion permeation through the extracellular vestibule and the transmembrane channel is well understood, whereas the specific ion conduction pathway through the intracellular domain is less clear. The intracellular domain starts with a short loop after the third transmembrane segment, followed by a short α-helical segment, a large unstructured loop, and finally, the membrane-associated MA-helix that continues into the last transmembrane segment. The MA-helices from all five subunits form the extension of the transmembrane ion channel and shape what has been described as a “closed vestibule,” with their lateral portals obstructed by loops and their cytosolic ends forming a tight hydrophobic constriction. The question remains whether the lateral portals or cytosolic constriction conduct ions upon channel opening. In our study, we used disulfide bond formation between pairs of engineered cysteines to probe the proximity and mobility of segments of the MA-helices most distal to the membrane bilayer. Our results indicate that the proximity and orientation for cysteine pairs at I409C/R410C, in close proximity to the lateral windows, and L402C/L403C, at the cytosolic ends of the MA-helices, are conducive for disulfide bond formation. Although conformational changes associated with gating promote cross-linking for I409C/R410C, which in turn decreases channel currents, cross-linking of L402C/L403C is functionally silent in macroscopic currents. These results support the hypothesis that concerted conformational changes open the lateral portals for ion conduction, rendering ion conduction through the vertical portal unlikely.

المؤلفون: James, Wp, Caterson, Id, Coutinho, W, Finer, N, VAN GAAL LF, Maggioni, Ap, TORP-PEDERSEN, C, Sharma, Am, Shepherd, Gm, Rode, Ra, Renz, Cl, Van Gaal LF, Torp-Pedersen, C, Pepine, C, Pocock, S, Drexler, H, Swedberg, K, Sleight, P, Armstrong, P, Kerr, D, Dagenais, G, Brophy, J, Avezum, A, Bogaty, P, Fabbri, G, Galli, M, Hildebrandt, P, Mann, J, Ostergren, J, Sherman, D, Zannad, F, Colquhoun, D, Hollanders, G, e Forti A, Costa, Cifkova, R, Toubro, S, Ziegler, O, Scherbaum, Wa, Jordan, J, Halmy, L, Ferrannini, E, Santini, F, Gonzalez, C, Narkiewicz, K, Hancu, N, Payer, J, Pascual, J, Wilding, J, Campbell, L, Carey, D, Gerstman, M, Karrasch, J, Lefkovits, J, Marks, J, Marks, S, Moses, R, Phillips, P, Proietto, J, Roberts, D, Roberts-Thomson, P, Shaw, J, Simpson, R, Singh, B, Singleton Jeffries, W, Stuckey, B, Boland, J, Brohet, C, Coucke, F, Dendale, P, Jouret, G, Kolanowski, J, Kutnowski, M, Martens, F, Muls, E, Peiffer, F, Penninckx, H, Scheen, A, Schoors, D, Vaerenberg, M, Van Cleemput, J, Van Crombrugge, P, Van Kuyk, M, Verhaegen, A, Wollaert, B, de Albuquerque DC, Appolinario, J, de Godoy Matos AF, Gross, Jl, Halpern, A, Kerr Saraiva JF, Milagres, R, Repetto, G, Suplicy, Hl, Zanella, Mt, Bednarova, J, Cepelak, V, Cerny, P, Hainer, V, Havranek, P, Homza, M, Jansa, P, Karlicek, M, Kolesar, J, Kotik, I, Kucera, D, Kuchar, J, Kunc, M, Kvapil, M, Linhart, A, Machova, V, Matuska, J, Oral, I, Pavlas, J, Pesatova, S, Povolny, J, Semrad, B, Smetana, K, Soucek, M, Svacina, S, Tesinsky, P, Urbanek, R, Wasserburger, B, Zachoval, R, Zahumensky, E, Zidkova, E, Astrup, A, Dominguez, H, Faber, J, Hilderbrant, P, Kober, L, Perrild, H, Richelsen, B, Sogaard, P, Svendsen, Ol, Urhammer, S, Archambeaud, F, Basdevant, A, Borys, Jm, Bringer, J, Brunetiere, C, Charpentier, G, Cocaul-André, M, Dabadie, H, Dubreuil, A, Estour, B, Gautier, Jf, Gibault, T, Halimi, S, Hespel, Jp, Issa Sayegh, M, Krempf, M, Laville, M, Lecerf, Jm, Louvet, Jp, Penfornis, A, Ritz, P, Schlienger, Jl, Schmitt, B, Valensi, P, Baar, M, Beermann, J, Bock, M, Boenner, G, Dammann, Hg, Diehm, C, Ditschuneit, H, Gadow, J, Gehlhar, S, Gessner, S, Guthersohn, A, Hamann, A, Hanefeld, M, Hasenfuss, G, Herzner, A, Heun, Kc, Heufelder, Ae, Hohensee, H, Jacob, S, Krings, P, Krätzig, B, Krosse, B, Lehmann, Rt, Mindt-Prüfert, S, Maisch, B, Pfeiffer, Af, Richard, F, Rose, B, Schmidt, E, Scholze, J, Schreckenberg, A, Stuebler, P, Walter, J, Wirth, A, Wunderlich, J, Abraham, G, Altorjay, A, Augusztin, G, Csaszar, A, Czuriga, I, Dinnyes, J, Gero, L, Gyimesi, A, Janosi, A, Kovacs, I, Liziczai, I, Majtenyi, A, Medvegy, M, Nadhazi, Z, Pados, G, Polak, G, Ronaszeki, A, Sido, Z, Simon, K, Anzà, C, Bevilacqua, M, Bosello, O, Chiariello, M, Cordera, R, Ferrari, E, Frittitta, L, Giorgino, R, Liuzzi, A, Malinverni, C, Di Mario, U, Melchionda, N, Occhi, G, Perticone, F, Pinchera, A, Pinelli, G, Rovera, G, Santeusanio, F, Urbinati, S, Alpizar-Salazar, M, Carrillo-Ortega, E, Fanghanel Salmon, G, Laviada-Molina, Ha, Madero, Ma, Rodriguez, G, Saldate, C, Sanchez-Castillo, Cp, Violante, Rm, Wacher, N, Zayas-Jaime, Fj, Zuniga-Guajardo, S, Adamiec, R, Banasiak, W, Chrusciel, P, Derlaga, B, Gebala, A, Gessek, J, Janik, K, Janion, M, Kalina, Z, Kozlowski, A, Kusnierz, B, Majcher, Z, Miekus, P, Niegowska, J, Okopien, B, Ostrowska, L, Pasowicz, M, Piepiorka, M, Pluta, W, Polaszewska-Muszynska, M, Ponikowski, P, Pupek-Musialik, D, Sawicki, A, Sobocik, H, Stankiewicz, A, Szpajer, M, Trojnar, R, Tykarski, A, Wrabec, K, Wyrzkowski, B, Zahorska-Markiewicz, B, Zalewski, M, Carrageta, M, Mendes Pedro MM, Parente Martins LM, dos Santos, L, Babes, A, Creteanu, G, Dan, Ga, Dragulescu, Si, Graur, M, Tirgoviste, Ci, Morosanu, M, Mota, M, Paveliu, Fs, Radoi, M, Ranetti, A, Totoian, I, Andre, I, Bugan, V, Cencarik, J, Csala, L, Farsky, S, Gonsorcik, J, Kamensky, G, Kmec, J, Krahulec, B, Kurian, R, Macek, V, Majercak, I, Micko, K, Mokan, M, Riecansky, I, Sojka, G, Uhliar, R, Urgeova, L, Vancik, J, Baro, Fm, Barrios Merino, A, Borras, Jl, Caixas, A, Cuatrecasas Cambra, G, Dominguez Escribano JR, Duran Garcia, S, Escobar-Jimenez, L, Esteva de Antonio, I, Formiguera Sala, X, Garcia-Luna, Pp, Garcia Robles, R, Gonzalez Albarran, O, Hernandez-Mijares, A, Martin Hidalgo, A, Masmiquel Comas, L, Morales Perez, F, Moreno Esteban, B, Pascual Izuel JM, Redon Mas, J, Ricart, W, Rubio, Ma, Ruilope, Lm, Salas-Salvado, J, Terroba Larumbe, M, Tinahones, F, de la Torre Casares ML, Vidal Cortada, J, Zuniga-Perez Lemaur, M, Abdulhakim, Ee, Adler, A, Barnett, Ah, Bodmer, C, Campbell, Iw, Chowdhury, T, Cleland, J, Cook, Rc, Dinneen, S, Donnachie, H, Haslam, Dw, Hillis, Gs, Horne, M, Howarth, Dj, Hughes, E, Jackson, S, Jones, Sc, Jones, Th, Kumar, S, Lean, M, Maroni, J, Mcinnes, G, Middleton, A, Morris, A, Newcombe, G, O'Kane, Kp, Pavel, Ic, Pawa, R, Perry, C, Pitts, C, Raja, A, Reckless, J, Robinson, J, Sarmiento, R, Soo, Sc, Taylor, S, Thomas, Ho, Thomson, Ma, Wilkins, M.

المصدر: The New England journal of medicine
James, W P T, Caterson, I D, Coutinho, W, Finer, N, Van Gaal, L F, Maggioni, A P, Torp-Pedersen, C T, Sharma, A M, Shepherd, G M, Rode, R A, Renz, C L, SCOUT Investigators & Richelsen, B 2010, ' Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects ', Briefings from the New England Journal of Medicine, vol. 363, no. 10, pp. 905-17 . https://doi.org/10.1056/NEJMoa1003114Test

مصطلحات موضوعية: Male, medicine.medical_specialty, Myocardial Infarction, Blood Pressure, Kaplan-Meier Estimate, Type 2 diabetes, Klinikai orvostudományok, Placebo, law.invention, Double-Blind Method, Randomized controlled trial, Weight loss, law, Internal medicine, Appetite Depressants, medicine, Humans, Obesity, Myocardial infarction, Stroke, Aged, business.industry, Hazard ratio, Orvostudományok, General Medicine, Middle Aged, Overweight, medicine.disease, Surgery, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Cardiology, Female, Human medicine, medicine.symptom, business, Cyclobutanes, Sibutramine, medicine.drug

الوصف: Background The long-term effects of sibutramine treatment on the rates of cardiovascular events and cardiovascular death among subjects at high cardiovascular risk have not been established. Methods We enrolled in our study 10,744 overweight or obese subjects, 55 years of age or older, with preexisting cardiovascular disease, type 2 diabetes mellitus, or both to assess the cardiovascular consequences of weight management with and without sibutramine in subjects at high risk for cardiovascular events. All the subjects received sibutramine in addition to participating in a weight-management program during a 6-week, single-blind, lead-in period, after which 9804 subjects underwent random assignment in a double-blind fashion to sibutramine (4906 subjects) or placebo (4898 subjects). The primary end point was the time from randomization to the first occurrence of a primary outcome event (nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death). Results The mean duration of treatment was 3.4 years. The mean weight loss during the lead-in period was 2.6 kg; after randomization, the subjects in the sibutramine group achieved and maintained further weight reduction (mean, 1.7 kg). The mean blood pressure decreased in both groups, with greater reductions in the placebo group than in the sibutramine group (mean difference, 1.2/1.4 mm Hg). The risk of a primary outcome event was 11.4% in the sibutramine group as compared with 10.0% in the placebo group (hazard ratio, 1.16; 95% confidence interval [CI], 1.03 to 1.31; P=0.02). The rates of nonfatal myocardial infarction and nonfatal stroke were 4.1% and 2.6% in the sibutramine group and 3.2% and 1.9% in the placebo group, respectively (hazard ratio for nonfatal myocardial infarction, 1.28; 95% CI, 1.04 to 1.57; P=0.02; hazard ratio for nonfatal stroke, 1.36; 95% CI, 1.04 to 1.77; P=0.03). The rates of cardiovascular death and death from any cause were not increased. Conclusions Subjects with preexisting cardiovascular conditions who were receiving long-term sibutramine treatment had an increased risk of nonfatal myocardial infarction and nonfatal stroke but not of cardiovascular death or death from any cause. (Funded by Abbott; ClinicalTrials.gov number, NCT00234832.)

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4edf26f01abf50ec8934da065b8ce86eTest
https://doi.org/10.1056/nejmoa1003114Test

المؤلفون: Pirayesh, Elham, Stuebler, Antonia G., Pandhare, Akash, Jansen, Michaela

المصدر: Biophysical Journal; February 2020, Vol. 118 Issue: 4 p934-943, 10p

مستخلص: The serotonin type 3A (5-HT3A) receptor is a homopentameric cation-selective member of the pentameric ligand-gated ion channel (pLGIC) superfamily. Members of this superfamily assemble from five subunits, each of which consists of three domains: extracellular (ECD), transmembrane (TMD), and intracellular domain (ICD). Previously, we have demonstrated that the 5-HT3A-ICD is required for the interaction between 5-HT3Aand the chaperone protein resistance to inhibitors of choline esterase (RIC-3). Additionally, we have shown that 5-HT3A-ICD fused to maltose-binding protein (MBP) directly interacts with RIC-3, without the involvement of other protein(s). To elucidate the molecular determinants of this interaction, we developed different MBP-fused 5-HT3A-ICD constructs by deleting large segments of its amino acid sequence. We expressed seven engineered ICDs in Escherichia coliand purified them to homogeneity. Using a RIC-3 affinity pull-down assay, the interaction between MBP-5HT3A-ICD constructs and RIC-3 was investigated. In summary, we identify a 24-amino-acid-long segment of the 5-HT3A-ICD as a molecular determinant for the interaction between the 5-HT3A-ICD and RIC-3.