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1. HSPB4/CRYAA Protect Photoreceptors during Retinal Detachment in Part through FAIM2 Regulation

Author

Cagri G. Besirli, Madhu Nath, Jingyu Yao, Mercy Pawar, Angela M. Myers, David Zacks, and Patrice E. Fort

Subjects
α-crystallin, Fas-apoptotic inhibitory molecule 2, Fas-mediated apoptosis, retinal detachment, photoreceptors, Medicine, Internal medicine, RC31-1245, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Our previous study discussed crystallin family induction in an experimental rat model of retinal detachment. Therefore, we attempted to evaluate the role of α-crystallin in photoreceptor survival in an experimental model of retinal detachment, as well as its association with the intrinsically neuroprotective protein Fas-apoptotic inhibitory molecule 2 (FAIM2). Separation of retina and RPE was induced in rat and mouse eyes by subretinal injection of hyaluronic acid. Retinas were subsequently analyzed for the presence αA-crystallin (HSPB4) and αB-crystallin (HSPB5) proteins using immunohistochemistry and immunoblotting. Photoreceptor death was analyzed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining and cell counts. The 661W cells subjected to FasL were used as a cell model of photoreceptor degeneration to assess the mechanisms of the protective effect of αA-crystallin and its dependence on its phosphorylation on T148. We further evaluated the interaction between FAIM2 and αA-crystallin using a co-immunoprecipitation assay. Our results showed that α-crystallin protein levels were rapidly induced in response to retinal detachment, with αA-crystallin playing a particularly important role in protecting photoreceptors during retinal detachment. Our data also show that the photoreceptor intrinsically neuroprotective protein FAIM2 is induced and interacts with α-crystallins following retinal detachment. Mechanistically, our work also demonstrated that the phosphorylation of αA-crystallin is important for the interaction of αA-crystallin with FAIM2 and their neuroprotective effect. Thus, αA-crystallin is involved in the regulation of photoreceptor survival during retinal detachment, playing a key role in the stabilization of FAIM2, serving as an important modulator of photoreceptor cell survival under chronic stress conditions.

Published
2024
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2. Alpha-crystallins protect photoreceptors during retinal detachment through FAIM2 regulation

Author

Cagri G. Besirli, Madhu Nath, Jingyu Yao, Mercy Pawar, Angela M. Myers, David Zacks, and Patrice E. Fort

Abstract

We evaluated the role of α-crystallin in photoreceptor survival in an experimental model of retinal detachment, and its association with Fas apoptosis inhibitory molecule 2 (FAIM2). Retina/RPE separation was induced in rat and mouse eyes by the subretinal injection of hyaluronic acid, 1%. Retinal tissues were analyzed for the presence αA-crystallin and αB-crystallin proteins using immunohistochemistry and immunoblot. Indices of photoreceptor death were analyzed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining and cell counts. The 661W cells subjected to FasL were used as a cell model of photoreceptor degeneration to assess the mechanisms of the protective effect of αA-crystallin and its phosphorylation on T148. In addition to the associated cell-death, FAIM2 and αA-crystallin interaction were evaluated using co-immunoprecipitation assay. α-Crystallin protein levels were rapidly induced in response to retinal detachment, with αA-crystallin playing a particularly important role in protecting photoreceptors during retinal detachment. Our data also shows that FAIM2, an intrinsic neuroprotective protein in photoreceptors, interacts with α-crystallins following retinal detachment. Mechanistically, our work also demonstrated that the phosphorylation of αA-crystallin is essential for the interaction of αA-crystallin with FAIM2 and their neuroprotective effect. Thus, αA-crystallin is involved in the regulation of photoreceptor survival during retinal detachment, playing a key role in the stabilization of FAIM2, an important modulator of photoreceptor cell survival under chronic stress condition.

Published
2022

3. Cisco Digital Network Architecture : Intent-based Networking for the Enterprise

Author

Tim Szigeti, David Zacks, Matthias Falkner, Simone Arena, Tim Szigeti, David Zacks, Matthias Falkner, and Simone Arena

Subjects
Computer network architectures
Abstract

The complete guide to transforming enterprise networks with Cisco DNA As networks become more complex and dynamic, organizations need better ways to manage and secure them. With the Cisco Digital Network Architecture, network operators can run entire network fabrics as a single, programmable system by defining rules that span their devices and move with their users. Using Cisco intent-based networking, you spend less time programming devices, managing configurations, and troubleshooting problems so you have more time for driving value from your network, your applications, and most of all, your users. This guide systematically introduces Cisco DNA, highlighting its business value propositions, design philosophy, tenets, blueprints, components, and solutions.Combining insider information with content previously scattered through multiple technical documents, it provides a single source for evaluation, planning, implementation, and operation. The authors bring together authoritative insights for multiple business and technical audiences. Senior executives will learn how DNA can help them drive digital transformation for competitive advantage. Technical decision-makers will discover powerful emerging solutions for their specific needs. Architects will find essential recommendations, interdependencies, and caveats for planning deployments. Finally, network operators will learn how to use DNA Center's modern interface to streamline, automate, and improve virtually any network management task. · Accelerate the digital transformation of your business by adopting an intent-based network architecture that is open, extensible, and programmable · Integrate virtualization, automation, analytics, and cloud services to streamline operations and create new business opportunities · Dive deep into hardware, software, and protocol innovations that lay the programmable infrastructure foundation for DNA · Virtualize advanced network functions for fast, easy, and flexible deployments · Translate business intent into device configurations and simplify, scale, and automate network operations using controllers · Use analytics to tune performance, plan capacity, prevent threats, and simplify troubleshooting · Learn how Software-Defined Access improves network flexibility, security, mobility, visibility, and performance · Use DNA Assurance to track the health of clients, network devices, and applications to reveal hundreds of actionable insights · See how DNA Application Policy supports granular application recognition and end-to-end treatment, for even encrypted applications · Identify malware, ransomware, and other threats in encrypted traffic

Published
2019

4. Guidelines for the use and interpretation of assays for monitoring autophagy

Author

Klionsky, D.J. Abdalla, F.C. Abeliovich, H. Abraham, R.T. Acevedo-Arozena, A. Adeli, K. Agholme, L. Agnello, M. Agostinis, P. Aguirre-Ghiso, J.A. Ahn, H.J. Ait-Mohamed, O. Ait-Si-Ali, S. Akematsu, T. Akira, S. Al-Younes, H.M. Al-Zeer, M.A. Albert, M.L. Albin, R.L. Alegre-Abarrategui, J. Aleo, M.F. Alirezaei, M. Almasan, A. Almonte-Becerril, M. Amano, A. Amaravadi, R. Amarnath, S. Amer, A.O. Andrieu-Abadie, N. Anantharam, V. Ann, D.K. Anoopkumar-Dukie, S. Aoki, H. Apostolova, N. Arancia, G. Aris, J.P. Asanuma, K. Asare, N.Y.O. Ashida, H. Askanas, V. Askew, D.S. Auberger, P. Baba, M. Backues, S.K. Baehrecke, E.H. Bahr, B.A. Bai, X.-Y. Bailly, Y. Baiocchi, R. Baldini, G. Balduini, W. Ballabio, A. Bamber, B.A. Bampton, E.T.W. Bánhegyi, G. Bartholomew, C.R. Bassham, D.C. Bast Jr., R.C. Batoko, H. Bay, B.-H. Beau, I. Béchet, D.M. Begley, T.J. Behl, C. Behrends, C. Bekri, S. Bellaire, B. Bendall, L.J. Benetti, L. Berliocchi, L. Bernardi, H. Bernassola, F. Besteiro, S. Bhatia-Kissova, I. Bi, X. Biard-Piechaczyk, M. Blum, J.S. Boise, L.H. Bonaldo, P. Boone, D.L. Bornhauser, B.C. Bortoluci, K.R. Bossis, I. Bost, F. Bourquin, J.-P. Boya, P. Boyer-Guittaut, M. Bozhkov, P.V. Brady, N.R. Brancolini, C. Brech, A. Brenman, J.E. Brennand, A. Bresnick, E.H. Brest, P. Bridges, D. Bristol, M.L. Brookes, P.S. Brown, E.J. Brumell, J.H. Brunetti-Pierri, N. Brunk, U.T. Bulman, D.E. Bultman, S.J. Bultynck, G. Burbulla, L.F. Bursch, W. Butchar, J.P. Buzgariu, W. Bydlowski, S.P. Cadwell, K. Cahová, M. Cai, D. Cai, J. Cai, Q. Calabretta, B. Calvo-Garrido, J. Camougrand, N. Campanella, M. Campos-Salinas, J. Candi, E. Cao, L. Caplan, A.B. Carding, S.R. Cardoso, S.M. Carew, J.S. Carlin, C.R. Carmignac, V. Carneiro, L.A.M. Carra, S. Caruso, R.A. Casari, G. Casas, C. Castino, R. Cebollero, E. Cecconi, F. Celli, J. Chaachouay, H. Chae, H.-J. Chai, C.-Y. Chan, D.C. Chan, E.Y. Chang, R.C.-C. Che, C.-M. Chen, C.-C. Chen, G.-C. Chen, G.-Q. Chen, M. Chen, Q. Chen, S.S.-L. Chen, W. Chen, X. Chen, X. Chen, X. Chen, Y.-G. Chen, Y. Chen, Y. Chen, Y.-J. Chen, Z. Cheng, A. Cheng, C.H.K. Cheng, Y. Cheong, H. Cheong, J.-H. Cherry, S. Chess-Williams, R. Cheung, Z.H. Chevet, E. Chiang, H.-L. Chiarelli, R. Chiba, T. Chin, L.-S. Chiou, S.-H. Chisari, F.V. Cho, C.H. Cho, D.-H. Choi, A.M.K. Choi, D. Choi, K.S. Choi, M.E. Chouaib, S. Choubey, D. Choubey, V. Chu, C.T. Chuang, T.-H. Chueh, S.-H. Chun, T. Chwae, Y.-J. Chye, M.-L. Ciarcia, R. Ciriolo, M.R. Clague, M.J. Clark, R.S.B. Clarke, P.G.H. Clarke, R. Codogno, P. Coller, H.A. Colombo, M.I. Comincini, S. Condello, M. Condorelli, F. Cookson, M.R. Coombs, G.H. Coppens, I. Corbalan, R. Cossart, P. Costelli, P. Costes, S. Coto-Montes, A. Couve, E. Coxon, F.P. Cregg, J.M. Crespo, J.L. Cronjé, M.J. Cuervo, A.M. Cullen, J.J. Czaja, M.J. D'Amelio, M. Darfeuille-Michaud, A. Davids, L.M. Davies, F.E. De Felici, M. De Groot, J.F. De Haan, C.A.M. De Martino, L. De Milito, A. De Tata, V. Debnath, J. Degterev, A. Dehay, B. Delbridge, L.M.D. Demarchi, F. Deng, Y.Z. Dengjel, J. Dent, P. Denton, D. Deretic, V. Desai, S.D. Devenish, R.J. Di Gioacchino, M. Di Paolo, G. Di Pietro, C. Díaz-Araya, G. Díaz-Laviada, I. Diaz-Meco, M.T. Diaz-Nido, J. Dikic, I. Dinesh-Kumar, S.P. Ding, W.-X. Distelhorst, C.W. Diwan, A. Djavaheri-Mergny, M. Dokudovskaya, S. Dong, Z. Dorsey, F.C. Dosenko, V. Dowling, J.J. Doxsey, S. Dreux, M. Drew, M.E. Duan, Q. Duchosal, M.A. Duff, K. Dugail, I. Durbeej, M. Duszenko, M. Edelstein, C.L. Edinger, A.L. Egea, G. Eichinger, L. Eissa, N.T. Ekmekcioglu, S. El-Deiry, W.S. Elazar, Z. Elgendy, M. Ellerby, L.M. Er Eng, K. Engelbrecht, A.-M. Engelender, S. Erenpreisa, J. Escalante, R. Esclatine, A. Eskelinen, E.-L. Espert, L. Espina, V. Fan, H. Fan, J. Fan, Q.-W. Fan, Z. Fang, S. Fang, Y. Fanto, M. Fanzani, A. Farkas, T. Farré, J.-C. Faure, M. Fechheimer, M. Feng, C.G. Feng, J. Feng, Q. Feng, Y. Fésüs, L. Feuer, R. Figueiredo-Pereira, M.E. Fimia, G.M. Fingar, D.C. Finkbeiner, S. Finkel, T. Finley, K.D. Fiorito, F. Fisher, E.A. Fisher, P.B. Flajolet, M. Florez-McClure, M.L. Florio, S. Fon, E.A. Fornai, F. Fortunato, F. Fotedar, R. Fowler, D.H. Fox, H.S. Franco, R. Frankel, L.B. Fransen, M. Fuentes, J.M. Fueyo, J. Fujii, J. Fujisaki, K. Fujita, E. Fukuda, M. Furukawa, R.H. Gaestel, M. Gailly, P. Gajewska, M. Galliot, B. Galy, V. Ganesh, S. Ganetzky, B. Ganley, I.G. Gao, F.-B. Gao, G.F. Gao, J. Garcia, L. Garcia-Manero, G. Garcia-Marcos, M. Garmyn, M. Gartel, A.L. Gatti, E. Gautel, M. Gawriluk, T.R. Gegg, M.E. Geng, J. Germain, M. Gestwicki, J.E. Gewirtz, D.A. Ghavami, S. Ghosh, P. Giammarioli, A.M. Giatromanolaki, A.N. Gibson, S.B. Gilkerson, R.W. Ginger, M.L. Ginsberg, H.N. Golab, J. Goligorsky, M.S. Golstein, P. Gomez-Manzano, C. Goncu, E. Gongora, C. Gonzalez, C.D. Gonzalez, R. González-Estévez, C. González-Polo, R.A. Gonzalez-Rey, E. Gorbunov, N.V. Gorski, S. Goruppi, S. Gottlieb, R.A. Gozuacik, D. Granato, G.E. Grant, G.D. Green, K.N. Gregorc, A. Gros, F. Grose, C. Grunt, T.W. Gual, P. Guan, J.-L. Guan, K.-L. Guichard, S.M. Gukovskaya, A.S. Gukovsky, I. Gunst, J. Gustafsson, A.B. Halayko, A.J. Hale, A.N. Halonen, S.K. Hamasaki, M. Han, F. Han, T. Hancock, M.K. Hansen, M. Harada, H. Harada, M. Hardt, S.E. Harper, J.W. Harris, A.L. Harris, J. Harris, S.D. Hashimoto, M. Haspel, J.A. Hayashi, S.-I. Hazelhurst, L.A. He, C. He, Y.-W. Hébert, M.-J. Heidenreich, K.A. Helfrich, M.H. Helgason, G.V. Henske, E.P. Herman, B. Herman, P.K. Hetz, C. Hilfiker, S. Hill, J.A. Hocking, L.J. Hofman, P. Hofmann, T.G. Höhfeld, J. Holyoake, T.L. Hong, M.-H. Hood, D.A. Hotamisligil, G.S. Houwerzijl, E.J. Høyer-Hansen, M. Hu, B. Hu, C.-A.A. Hu, H.-M. Hua, Y. Huang, C. Huang, J. Huang, S. Huang, W.-P. Huber, T.B. Huh, W.-K. Hung, T.-H. Hupp, T.R. Hur, G.M. Hurley, J.B. Hussain, S.N.A. Hussey, P.J. Hwang, J.J. Hwang, S. Ichihara, A. Ilkhanizadeh, S. Inoki, K. Into, T. Iovane, V. Iovanna, J.L. Ip, N.Y. Isaka, Y. Ishida, H. Isidoro, C. Isobe, K.-I. Iwasaki, A. Izquierdo, M. Izumi, Y. Jaakkola, P.M. Jäättelä, M. Jackson, G.R. Jackson, W.T. Janji, B. Jendrach, M. Jeon, J.-H. Jeung, E.-B. Jiang, H. Jiang, H. Jiang, J.X. Jiang, M. Jiang, Q. Jiang, X. Jiménez, A. Jin, M. Jin, S. Joe, C.O. Johansen, T. Johnson, D.E. Johnson, G.V.W. Jones, N.L. Joseph, B. Joseph, S.K. Joubert, A.M. Juhász, G. Juillerat-Jeanneret, L. Jung, C.H. Jung, Y.-K. Kaarniranta, K. Kaasik, A. Kabuta, T. Kadowaki, M. Kagedal, K. Kamada, Y. Kaminskyy, V.O. Kampinga, H.H. Kanamori, H. Kang, C. Kang, K.B. Il Kang, K. Kang, R. Kang, Y.-A. Kanki, T. Kanneganti, T.-D. Kanno, H. Kanthasamy, A.G. Kanthasamy, A. Karantza, V. Kaushal, G.P. Kaushik, S. Kawazoe, Y. Ke, P.-Y. Kehrl, J.H. Kelekar, A. Kerkhoff, C. Kessel, D.H. Khalil, H. Kiel, J.A.K.W. Kiger, A.A. Kihara, A. Kim, D.R. Kim, D.-H. Kim, D.-H. Kim, E.-K. Kim, H.-R. Kim, J.-S. Kim, J.H. Kim, J.C. Kim, J.K. Kim, P.K. Kim, S.W. Kim, Y.-S. Kim, Y. Kimchi, A. Kimmelman, A.C. King, J.S. Kinsella, T.J. Kirkin, V. Kirshenbaum, L.A. Kitamoto, K. Kitazato, K. Klein, L. Klimecki, W.T. Klucken, J. Knecht, E. Ko, B.C.B. Koch, J.C. Koga, H. Koh, J.-Y. Koh, Y.H. Koike, M. Komatsu, M. Kominami, E. Kong, H.J. Kong, W.-J. Korolchuk, V.I. Kotake, Y. Koukourakis, M.I. Kouri Flores, J.B. Kovács, A.L. Kraft, C. Krainc, D. Krämer, H. Kretz-Remy, C. Krichevsky, A.M. Kroemer, G. Krüger, R. Krut, O. Ktistakis, N.T. Kuan, C.-Y. Kucharczyk, R. Kumar, A. Kumar, R. Kumar, S. Kundu, M. Kung, H.-J. Kurz, T. Kwon, H.J. La Spada, A.R. Lafont, F. Lamark, T. Landry, J. Lane, J.D. Lapaquette, P. Laporte, J.F. László, L. Lavandero, S. Lavoie, J.N. Layfield, R. Lazo, P.A. Le, W. Le Cam, L. Ledbetter, D.J. Lee, A.J.X. Lee, B.-W. Lee, G.M. Lee, J. Lee, J.-H. Lee, M. Lee, M.-S. Lee, S.H. Leeuwenburgh, C. Legembre, P. Legouis, R. Lehmann, M. Lei, H.-Y. Lei, Q.-Y. Leib, D.A. Leiro, J. Lemasters, J.J. Lemoine, A. Lesniak, M.S. Lev, D. Levenson, V.V. Levine, B. Levy, E. Li, F. Li, J.-L. Li, L. Li, S. Li, W. Li, X.-J. Li, Y.-B. Li, Y.-P. Liang, C. Liang, Q. Liao, Y.-F. Liberski, P.P. Lieberman, A. Lim, H.J. Lim, K.-L. Lim, K. Lin, C.-F. Lin, F.-C. Lin, J. Lin, J.D. Lin, K. Lin, W.-W. Lin, W.-C. Lin, Y.-L. Linden, R. Lingor, P. Lippincott-Schwartz, J. Lisanti, M.P. Liton, P.B. Liu, B. Liu, C.-F. Liu, K. Liu, L. Liu, Q.A. Liu, W. Liu, Y.-C. Liu, Y. Lockshin, R.A. Lok, C.-N. Lonial, S. Loos, B. Lopez-Berestein, G. López-Otín, C. Lossi, L. Lotze, M.T. Lõw, P. Lu, B. Lu, B. Lu, B. Lu, Z. Luciano, F. Lukacs, N.W. Lund, A.H. Lynch-Day, M.A. Ma, Y. Macian, F. MacKeigan, J.P. Macleod, K.F. Madeo, F. Maiuri, L. Maiuri, M.C. Malagoli, D. Malicdan, M.C.V. Malorni, W. Man, N. Mandelkow, E.-M. Manon, S. Manov, I. Mao, K. Mao, X. Mao, Z. Marambaud, P. Marazziti, D. Marcel, Y.L. Marchbank, K. Marchetti, P. Marciniak, S.J. Marcondes, M. Mardi, M. Marfe, G. Mariño, G. Markaki, M. Marten, M.R. Martin, S.J. Martinand-Mari, C. Martinet, W. Martinez-Vicente, M. Masini, M. Matarrese, P. Matsuo, S. Matteoni, R. Mayer, A. Mazure, N.M. McConkey, D.J. McConnell, M.J. McDermott, C. McDonald, C. McInerney, G.M. McKenna, S.L. McLaughlin, B. McLean, P.J. McMaster, C.R. McQuibban, G.A. Meijer, A.J. Meisler, M.H. Meléndez, A. Melia, T.J. Melino, G. Mena, M.A. Menendez, J.A. Menna-Barreto, R.F.S. Menon, M.B. Menzies, F.M. Mercer, C.A. Merighi, A. Merry, D.E. Meschini, S. Meyer, C.G. Meyer, T.F. Miao, C.-Y. Miao, J.-Y. Michels, P.A.M. Michiels, C. Mijaljica, D. Milojkovic, A. Minucci, S. Miracco, C. Miranti, C.K. Mitroulis, I. Miyazawa, K. Mizushima, N. Mograbi, B. Mohseni, S. Molero, X. Mollereau, B. Mollinedo, F. Momoi, T. Monastyrska, I. Monick, M.M. Monteiro, M.J. Moore, M.N. Mora, R. Moreau, K. Moreira, P.I. Moriyasu, Y. Moscat, J. Mostowy, S. Mottram, J.C. Motyl, T. Moussa, C.E.-H. Müller, S. Muller, S. Münger, K. Münz, C. Murphy, L.O. Murphy, M.E. Musarò, A. Mysorekar, I. Nagata, E. Nagata, K. Nahimana, A. Nair, U. Nakagawa, T. Nakahira, K. Nakano, H. Nakatogawa, H. Nanjundan, M. Naqvi, N.I. Narendra, D.P. Narita, M. Navarro, M. Nawrocki, S.T. Nazarko, T.Y. Nemchenko, A. Netea, M.G. Neufeld, T.P. Ney, P.A. Nezis, I.P. Nguyen, H.P. Nie, D. Nishino, I. Nislow, C. Nixon, R.A. Noda, T. Noegel, A.A. Nogalska, A. Noguchi, S. Notterpek, L. Novak, I. Nozaki, T. Nukina, N. Nürnberger, T. Nyfeler, B. Obara, K. Oberley, T.D. Oddo, S. Ogawa, M. Ohashi, T. Okamoto, K. Oleinick, N.L. Oliver, F.J. Olsen, L.J. Olsson, S. Opota, O. Osborne, T.F. Ostrander, G.K. Otsu, K. Ou, J.-H.J. Ouimet, M. Overholtzer, M. Ozpolat, B. Paganetti, P. Pagnini, U. Pallet, N. Palmer, G.E. Palumbo, C. Pan, T. Panaretakis, T. Pandey, U.B. Papackova, Z. Papassideri, I. Paris, I. Park, J. Park, O.K. Parys, J.B. Parzych, K.R. Patschan, S. Patterson, C. Pattingre, S. Pawelek, J.M. Peng, J. Perlmutter, D.H. Perrotta, I. Perry, G. Pervaiz, S. Peter, M. Peters, G.J. Petersen, M. Petrovski, G. Phang, J.M. Piacentini, M. Pierre, P. Pierrefite-Carle, V. Pierron, G. Pinkas-Kramarski, R. Piras, A. Piri, N. Platanias, L.C. Pöggeler, S. Poirot, M. Poletti, A. Poüs, C. Pozuelo-Rubio, M. Prætorius-Ibba, M. Prasad, A. Prescott, M. Priault, M. Produit-Zengaffinen, N. Progulske-Fox, A. Proikas-Cezanne, T. Przedborski, S. Przyklenk, K. Puertollano, R. Puyal, J. Qian, S.-B. Qin, L. Qin, Z.-H. Quaggin, S.E. Raben, N. Rabinowich, H. Rabkin, S.W. Rahman, I. Rami, A. Ramm, G. Randall, G. Randow, F. Rao, V.A. Rathmell, J.C. Ravikumar, B. Ray, S.K. Reed, B.H. Reed, J.C. Reggiori, F. Régnier-Vigouroux, A. Reichert, A.S. Reiners Jr., J.J. Reiter, R.J. Ren, J. Revuelta, J.L. Rhodes, C.J. Ritis, K. Rizzo, E. Robbins, J. Roberge, M. Roca, H. Roccheri, M.C. Rocchi, S. Rodemann, H.P. De Córdoba, S.R. Rohrer, B. Roninson, I.B. Rosen, K. Rost-Roszkowska, M.M. Rouis, M. Rouschop, K.M.A. Rovetta, F. Rubin, B.P. Rubinsztein, D.C. Ruckdeschel, K. Rucker III, E.B. Rudich, A. Rudolf, E. Ruiz-Opazo, N. Russo, R. Rusten, T.E. Ryan, K.M. Ryter, S.W. Sabatini, D.M. Sadoshima, J. Saha, T. Saitoh, T. Sakagami, H. Sakai, Y. Salekdeh, G.H. Salomoni, P. Salvaterra, P.M. Salvesen, G. Salvioli, R. Sanchez, A.M.J. Sánchez-Alcázar, J.A. Sánchez-Prieto, R. Sandri, M. Sankar, U. Sansanwal, P. Santambrogio, L. Saran, S. Sarkar, S. Sarwal, M. Sasakawa, C. Sasnauskiene, A. Sass, M. Sato, K. Sato, M. Schapira, A.H.V. Scharl, M. Schätzl, H.M. Scheper, W. Schiaffino, S. Schneider, C. Schneider, M.E. Schneider-Stock, R. Schoenlein, P.V. Schorderet, D.F. Schüller, C. Schwartz, G.K. Scorrano, L. Sealy, L. Seglen, P.O. Segura-Aguilar, J. Seiliez, I. Seleverstov, O. Sell, C. Seo, J.B. Separovic, D. Setaluri, V. Setoguchi, T. Settembre, C. Shacka, J.J. Shanmugam, M. Shapiro, I.M. Shaulian, E. Shaw, R.J. Shelhamer, J.H. Shen, H.-M. Shen, W.-C. Sheng, Z.-H. Shi, Y. Shibuya, K. Shidoji, Y. Shieh, J.-J. Shih, C.-M. Shimada, Y. Shimizu, S. Shintani, T. Shirihai, O.S. Shore, G.C. Sibirny, A.A. Sidhu, S.B. Sikorska, B. Silva-Zacarin, E.C.M. Simmons, A. Simon, A.K. Simon, H.-U. Simone, C. Simonsen, A. Sinclair, D.A. Singh, R. Sinha, D. Sinicrope, F.A. Sirko, A. Siu, P.M. Sivridis, E. Skop, V. Skulachev, V.P. Slack, R.S. Smaili, S.S. Smith, D.R. Soengas, M.S. Soldati, T. Song, X. Sood, A.K. Soong, T.W. Sotgia, F. Spector, S.A. Spies, C.D. Springer, W. Srinivasula, S.M. Stefanis, L. Steffan, J.S. Stendel, R. Stenmark, H. Stephanou, A. Stern, S.T. Sternberg, C. Stork, B. Strålfors, P. Subauste, C.S. Sui, X. Sulzer, D. Sun, J. Sun, S.-Y. Sun, Z.-J. Sung, J.J.Y. Suzuki, K. Suzuki, T. Swanson, M.S. Swanton, C. Sweeney, S.T. Sy, L.-K. Szabadkai, G. Tabas, I. Taegtmeyer, H. Tafani, M. Takács-Vellai, K. Takano, Y. Takegawa, K. Takemura, G. Takeshita, F. Talbot, N.J. Tan, K.S.W. Tanaka, K. Tanaka, K. Tang, D. Tang, D. Tanida, I. Tannous, B.A. Tavernarakis, N. Taylor, G.S. Taylor, G.A. Taylor, J.P. Terada, A.S. Terman, A. Tettamanti, G. Thevissen, K. Thompson, C.B. Thorburn, A. Thumm, M. Tian, F. Tian, Y. Tocchini-Valentini, G. Tolkovsky, A.M. Tomino, Y. Tönges, L. Tooze, S.A. Tournier, C. Tower, J. Towns, R. Trajkovic, V. Travassos, L.H. Tsai, T.-F. Tschan, M.P. Tsubata, T. Tsung, A. Turk, B. Turner, L.S. Tyagi, S.C. Uchiyama, Y. Ueno, T. Umekawa, M. Umemiya-Shirafuji, R. Unni, V.K. Vaccaro, M.I. Valente, E.M. Van Den Berghe, G. Van Der Klei, I.J. Van Doorn, W.G. Van Dyk, L.F. Van Egmond, M. Van Grunsven, L.A. Vandenabeele, P. Vandenberghe, W.P. Vanhorebeek, I. Vaquero, E.C. Velasco, G. Vellai, T. Vicencio, J.M. Vierstra, R.D. Vila, M. Vindis, C. Viola, G. Viscomi, M.T. Voitsekhovskaja, O.V. Von Haefen, C. Votruba, M. Wada, K. Wade-Martins, R. Walker, C.L. Walsh, C.M. Walter, J. Wan, X.-B. Wang, A. Wang, C. Wang, D. Wang, F. Wang, F. Wang, G. Wang, H. Wang, H.-G. Wang, H.-D. Wang, J. Wang, K. Wang, M. Wang, R.C. Wang, X. Wang, X. Wang, Y.-J. Wang, Y. Wang, Z. Wang, Z.C. Wang, Z. Wansink, D.G. Ward, D.M. Watada, H. Waters, S.L. Webster, P. Wei, L. Weihl, C.C. Weiss, W.A. Welford, S.M. Wen, L.-P. Whitehouse, C.A. Whitton, J.L. Whitworth, A.J. Wileman, T. Wiley, J.W. Wilkinson, S. Willbold, D. Williams, R.L. Williamson, P.R. Wouters, B.G. Wu, C. Wu, D.-C. Wu, W.K.K. Wyttenbach, A. Xavier, R.J. Xi, Z. Xia, P. Xiao, G. Xie, Z. Xie, Z. Xu, D.-Z. Xu, J. Xu, L. Xu, X. Yamamoto, A. Yamamoto, A. Yamashina, S. Yamashita, M. Yan, X. Yanagida, M. Yang, D.-S. Yang, E. Yang, J.-M. Yang, S.Y. Yang, W. Yang, W.Y. Yang, Z. Yao, M.-C. Yao, T.-P. Yeganeh, B. Yen, W.-L. Yin, J.-J. Yin, X.-M. Yoo, O.-J. Yoon, G. Yoon, S.-Y. Yorimitsu, T. Yoshikawa, Y. Yoshimori, T. Yoshimoto, K. You, H.J. Youle, R.J. Younes, A. Yu, L. Yu, L. Yu, S.-W. Yu, W.H. Yuan, Z.-M. Yue, Z. Yun, C.-H. Yuzaki, M. Zabirnyk, O. Silva-Zacarin, E. David Zacks, E. Zacksenhaus, L. Zaffaroni, N. Zakeri, Z. Zeh III, H.J. Zeitlin, S.O. Zhang, H. Zhang, H.-L. Zhang, J. Zhang, J.-P. Zhang, L. Zhang, L. Zhang, M.-Y. Zhang, X.D. Zhao, M. Zhao, Y.-F. Zhao, Y. Zhao, Z.J. Zheng, X. Zhivotovsky, B. Zhong, Q. Zhou, C.-Z. Zhu, C. Zhu, W.-G. Zhu, X.-F. Zhu, X. Zhu, Y. Zoladek, T. Zong, W.-X. Zorzano, A. Zschocke, J. Zuckerbraun, B.

Abstract

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field. © 2012 Landes Bioscience.

Published
2012

5. Tuberculosis case finding; a comparison of the effectiveness of various roentgenographic and photofluorographic methods

Author

W. Edward Chamberlain, David Zacks, Percy E. Schools, Jacob Yerushalmy, Carl C. Birkelo, and Paul S. Phelps

Subjects
medicine.medical_specialty, business.industry, Radiography, Adult population, Photofluorography, Diagnostic aid, Surgery, medicine, Case finding, Humans, Tuberculosis, Medical physics, business, Lung, Tuberculosis, Pulmonary
Abstract

Within a relatively short time photofluorography has been transformed from a crude experiment to an efficient diagnostic aid. It may be estimated that within the last six years some 20 million Americans have had x-ray examinations of the chest. The vast majority of these would not have had this service if they had had to depend on the conventional 14 by 17 inch celluloid film. The outlook for the future is that mass radiography will further expand and that a majority of the adult population will receive this service. The radiographic technics and sizes most commonly used are 35 mm. photofluorography, 4 by 10 inch stereophotofluorography, roentgenography on 14 by 17 inch paper and film negatives and, in recent months, 70 mm. photofluorography. Individual preferences for one or the other of these technics are based, as far as can be determined, on considerations of economy, ease of operation, individual likes

Published
2010

6. Incidence, Risk Factors, and Timing of Elevated Intraocular Pressure After Intravitreal Triamcinolone Acetonide Injection for Macular Edema Secondary to Retinal Vein Occlusion

Author

Peter Kaiser, Rony Zachariah, Magdalena G. Krzystolik, Ingrid Scott, David DiLoreto, Thomas Ciulla, David Zacks, and Leandro Zacharias

Subjects
Adult, Male, Intraocular pressure, medicine.medical_specialty, Time Factors, Visual acuity, Triamcinolone acetonide, genetic structures, Population, Glaucoma, Triamcinolone Acetonide, Macular Edema, Article, law.invention, Tonometry, Ocular, Randomized controlled trial, Risk Factors, law, Ophthalmology, Retinal Vein Occlusion, medicine, Humans, education, Glucocorticoids, Macular edema, Intraocular Pressure, Aged, Aged, 80 and over, education.field_of_study, business.industry, Incidence, Middle Aged, medicine.disease, Acetonide, eye diseases, Intravitreal Injections, Female, Ocular Hypertension, medicine.symptom, business, medicine.drug
Abstract

The Standard of Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) Study showed that intravitreal triamcinolone acetonide (IVTA) is effective at reducing macular edema and improving visual acuity in participants with retinal vein occlusion. Secondary analysis of the incidence, risk factors, and timing of intraocular pressure (IOP) elevation occurring after IVTA provides guidance for clinical decision making and management of patients treated with IVTA.To investigate the incidence, risk factors, and time course of IOP elevation in participants in the SCORE Study.Secondary analysis conducted from August through December 2014 of a prospective, randomized clinical trial featuring an evaluable population conducted at 75 clinical sites. Six hundred eighty-two patients with macular edema secondary to retinal vein occlusion were enrolled in the study. The SCORE Study enrollment period ran from November 4, 2004, to February 29, 2008, with participant follow-up ending February 28, 2009.Study participants were randomized to standard of care, 1 mg of IVTA, or 4 mg of IVTA therapy and followed up for a mean (SD) of 24.7 (10.3) months.Intraocular pressure elevation greater than 10 mm Hg from baseline.Kaplan-Meier incidences of IOP elevation greater than 10 mm Hg from baseline at 36 months were 0.02 (95% CI, 0.01-0.06), 0.09 (95% CI, 0.05-0.14), and 0.45 (95% CI, 0.38-0.53) in the standard of care, 1-mg IVTA, and 4-mg IVTA groups, respectively. The rates of IOP-related events were higher for the 4-mg IVTA group compared with the other groups (P ≤ .001 for main outcome measure). Younger age, 4-mg IVTA vs 1-mg IVTA treatment, and higher baseline IOP were found to confer greater risk for IOP-related events (P .05 for all). The median number of days from time of first injection to IOP elevation greater than 10 mm Hg from baseline was 34.0 and 52.5 days in participants treated with 1-mg and 4-mg IVTA, respectively.Intravitreal triamcinolone acetonide injection therapy, in particular the 4-mg dose, is associated with an increased risk for IOP elevation. The risk factors for an IOP-related event include higher treatment dose, younger age, and higher baseline IOP. Intraocular pressure-related events may take several months from the time of first IVTA injection to occur. Clinicians should be mindful of these risk factors when assessing the risks and benefits of IVTA therapy and also of the need for long-term follow-up of participants at risk for this complication.clinicaltrials.gov Identifier: NCT00105027.

Published
2015

8. Central serous chorioretinopathy and risk for obstructive sleep apnea.

Author

Thellea Leveque, Le Yu, Ronald Chervin, and David Zacks

Abstract

Abstract  Patients with obstructive sleep apnea (OSA), in comparison to controls, have increased levels of circulating epinephrine and norepinephrine, both of which are risk factors for the development of central serous chorioretinopathy (CSCR). The aim of this pilot study was to investigate the frequency of symptoms that suggest OSA in CSCR patients and normal controls. The Berlin Questionnaire, a validated research tool to assess risk for OSA, was administered to 29 patients who met the criteria for active, acute, non-steroid-induced CSCR and 29 controls matched for age and sex. In this retrospective case-controlled study, the main outcome measure was increased risk for OSA. The mean age of the patients was 47.8 years (range 29–72) and the mean age of controls was 47.3 years (range 25–70). Seventy-six percent (22) of both groups were men. Survey scores showed 58.6% (17) of patients with CSCR to be at an increased risk for OSA compared to 31.0% (nine) of controls. A conditional logistic regression analysis showed that the CSCR group had a higher proportion with an increased risk for OSA compared to the control group (odds ratio=3.67; 95% CI: 1.02, 13.14; P = 0.046). Patients with CSCR may be more likely than other adults to have OSA, and screening for this sleep disorder should be considered in this population. Further research is warranted to determine whether sleep apnea may contribute to the development of CSCR, and to assess whether treatment of sleep apnea might offer a new therapeutic option for some patients with CSCR. [ABSTRACT FROM AUTHOR]

Published
2007
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9. The incidence of tuberculous infection in school children

Author

David Zacks, A.K. Krause, and Henry D. Chadwick

Subjects
Pulmonary and Respiratory Medicine, education.field_of_study, medicine.medical_specialty, Tuberculosis, Framingham Risk Score, business.industry, Incidence (epidemiology), Population, Tuberculin, Disease, medicine.disease, Surgery, medicine, Young adult, education, Tuberculin test, business, Demography
Abstract

Summary The percentage of reactors in the 42,000 children studied in this series shows a gradual trend upward from 21 per cent, infections at age 5, 28 per cent, at age 10 to 35 per cent, at age 15. The average percentage for the whole group is 28 per cent. Different sections in the same city may show a wide variation in the percentage of reactors. It was found in one city of 60,000 that the number of children reacting to the tuberculin test in different school districts varied from 11 per cent, to 60 per cent. The number of reactors increases with the opportunities that the child has for contact with bacilli carriers. Chronic forms of pulmonary tuberculosis, such as are found in granite quarry workers, expose and infect more children than the more acute cases, who live a much shorter time after the disease becomes infectious. Crowded living conditions afford more opportunities for contact and congested areas show a higher percentage of infection. Twice as many reactors are found among children with a history of direct contact with a case of pulmonary tuberculosis. Another factor to be taken into account is bovine infection. In a few rural towns with a scattered population and less than the average number of pulmonary tuberculosis deaths, we found as high as 38 per cent, reactors. The majority of the small towns, however, show a little less than the average percentage for the State as a whole. Susceptibility to infection appears to be equal in different nationalities. The tubercle bacillus infects the children of different nationalities to an equal degree when similar conditions for contact with carriers are present. The boys of the Irish, Canadian and Teuton groups in this series show a much higher incidence of infection than the girls, for which no explanation is offered. The tuberculin survey made in 1917 by the Framingham Demonstration and the one made in 1926 by the State Clinic for the same age group, 6 and 7 years, shows a reduction of 23 per cent. The children in the 1926 group averaged 5′7 years older than those examined in 1917, but the percentage of reactors was 8′5 per cent. less. While the numbers considered in this comparison are small, the marked reduction in infection checks up with the reduced death-rate in Massachusetts for all forms of tuberculosis, which declined from 144 per 100,000 in 1917 to 73 in 1927. Three important factors have operated to bring about a reduction in the number of infected children:— (1) The steady decline in the death-rate results in fewer persons with tuberculosis at large in the community to spread infection. (2) The State has a little more than one bed for each tuberculosis death in which to segregate cases of tuberculosis and so further reduce the foci of infection in the homes of these patients. (3) Pasteurized milk is now available for about 60 per cent, of the population of the State and by so much is the possibility of bovine infection curtailed. The efforts made in the past to eradicate tuberculosis from the herds in this State have been sporadic and therefore ineffective. The past year, however, a systematic plan for area testing has been put into effect, which promises better results. This plan deserves the hearty support of the public. The sources of tubercle bacilli, both human and bovine, being thus decreased, must result in fewer persons being exposed to infection. Therefore, we should expect to find a reduction in the number of reactors. Such indeed seems to be demonstrated by our survey. The tuberculin survey herein reported will afford a basis by which to measure the incidence of infection when comparable studies are made in future years. Tuberculous infection is no longer universal in Massachusetts. The increase in infection from five years to fifteen years averages one point per year. Granting that the same rate continued, the children now 15 years of age would show but 50 per cent, infection when 30 years old. A tuberculin test of a large, group of adults might show that to be the maximum percentage of infection even now. With the marked decrease in the number of infected persons, tuberculin tests become of diagnostic value in young adults, as well as in young children. If intracutaneous tests are made with increasing doses of tuberculin, beginning with 0·01 mg., then with 1 mg., and finally with 10 mg., without reaction, tuberculosis can be excluded in many persons suspected of having that disease. In such cases a negative test is of great value.

Published
1930

11. Development of Tuberculosis in Infected Children

Author

David Zacks, Alton S. Pope, and Philip E. Sartwell

Subjects
Pediatrics, medicine.medical_specialty, Tuberculosis, business.industry, Prevalence, Tuberculin, Articles, General Medicine, medicine.disease, medicine.anatomical_structure, Fibrosis, Immunology, medicine, business, Progressive disease, Sensitization, Calcification
Abstract

IN laboratory animals where time of infection and dose of bacilli can be controlled there is substantial agreement that primary infection with tuberculosis, if not overwhelming, results in a measurably increased resistance to subsequent inoculations with tubercle bacilli.1' 2, 3 In man the picture is less clear. Although the typical parenchymal infiltration of primary infection, followed by resolution, fibrosis and calcification, is not infrequently observed roentgenologically, the exact date of reinfection and the duration of exposure are rarely known, and the dosage of bacilli is wholly problematical. Furthermore, it has not been demonstrated how far the results of inoculation experiments with tuberculosis in laboratory animals can be applied to natural infection in man. From a public health standpoint the relationship between primary infection with tuberculosis and the development of subsequent progressive disease has become a problem of major importance. Is a primary infection acquired during childhood a relative safeguard against subsequent exposure? or does the sensitization acquired through such infection result in increased susceptibility to destructive lesions? Much evidence might be cited to

Published
1939

13. Socioeconomic Aspects of Disease

Author

Robert W. Hyde, Lowell V. Kingsley, and David Zacks

Subjects
business.industry, Environmental health, Medicine, General Medicine, Disease, business, Socioeconomic status
Published
1943

15. THE PROBLEM OF TUBERCULOSIS IN SCHOOL CHILDREN

Author

David Zacks

Subjects
Philosophy, medicine.medical_specialty, Tuberculosis, business.industry, Family medicine, Public Health, Environmental and Occupational Health, medicine, medicine.disease, business, Education
Published
1942

18. Alterations in the Bimodal Gas Exchange of the African Catfish Clarias lazera

Author

David Zacks and Amos Ar

Subjects
geography, Order cypriniformes, geography.geographical_feature_category, biology, STREAMS, biology.organism_classification, Photosynthesis, Swamp, Clarias, Fishery, chemistry.chemical_compound, chemistry, Botany, Carbon dioxide, East africa, Catfish
Abstract

The African catfish, an air-breathing teleost belonging to the order Cypriniformes family Claridae, is found in East Africa, including Sudan and Egypt, and in Israel. It inhabits freshwater pools, streams, lakes, and swamps where water exhibits variable levels of oxygen and carbon dioxide pressures (\(P{W_{O_2}} \) and \(P{W_{O_2}}\) respectively) both seasonally and daily. \(P{W_{O_2}}\) may vary from oversaturation during daytimes with strong photosynthetic activity, down to very low values at nights in swamps with microbial activity (Abdel Magid 1971; Dejours 1975; Jordan 1976; Moussa 1956, 1957; Munshi 1961; Thomas et al. 1983).

Published
1989

22. Development of Tuberculosis in Infected Children

Author

Jean Downes, Philip E. Sartwell, Wade H. Frost, Alton S. Pope, and David Zacks

Subjects
Tuberculosis, business.industry, medicine, General Medicine, medicine.disease, business, Virology
Published
1940

23. HILUM TUBERCULOSIS

Author

David Zacks

Subjects
medicine.medical_specialty, Tuberculosis, Lung, business.industry, Public health, General surgery, Hilum (biology), Roentgen, Disease, medicine.disease, Surgery, Lesion, symbols.namesake, Lymphatic system, medicine.anatomical_structure, medicine, symbols, medicine.symptom, business
Abstract

In the weekly report of the state health department to the Boston Medical and Surgical Journal 1 appears for the first time the item, "Tuberculosis, hilum, sixty-one cases." This, of course, is a direct result of the activity of the Massachusetts Department of Public Health in finding bronchial gland tuberculosis among the school children of the state. This means that the disease is now recognized as an entity and that it can be diagnosed with more or less certainty. In order to realize fully the significance of this report, it is necessary to trace briefly the history of this disease. Up till 1910-1911, it was generally accepted that tuberculosis begins at the apex of the lung, particularly the right apex. Already there were those, however, who believed in pulmonary lymphatic tuberculosis, some holding that it was primary, and some, secondary to a pulmonary lesion. Lymph gland tuberculosis was thought to

Published
1926

24. OBSERVATIONS IN THE UNDERWEIGHT CLINICS IN MASSACHUSETTS

Author

Henry D. Chadwick and David Zacks

Subjects
medicine.medical_specialty, Pediatrics, Tuberculosis, business.industry, Public health, General Medicine, Disease, medicine.disease, Pulmonary tuberculosis, medicine, Underweight, medicine.symptom, Adult type, business
Abstract

The Massachusetts Department of Public Health is just completing the third year of its ten-year program. The plan, as outlined in the beginning, proposed the examination of the following groups of school children: Children 10 per cent or more underweight for height. Contacts: Those known to be exposed to human tuberculosis in the homes. Specials: Those not in either of the foregoing classes, but who were known to be in poor health. The primary purpose of this work was to find the children who showed some evidence of tuberculous disease. Knowing that children with the juvenile type of tuberculosis responded well to treatment, it was felt that if they could be discovered and given proper care at the right time many cases of the adult type of pulmonary tuberculosis would be prevented in later years. During the first year about 10,000 children were examined; during the second year, 20,000, and

Published
1927

25. Switching to less expensive blindness drug could save medicare part B $18 billion over a ten-year period.

Author

Hutton D, Newman-Casey PA, Tavag M, Zacks D, and Stein J

Subjects
Antibodies, Monoclonal, Humanized adverse effects, Bevacizumab, Humans, Ranibizumab, United States, Antibodies, Monoclonal, Humanized economics, Antibodies, Monoclonal, Humanized therapeutic use, Blindness drug therapy, Blindness economics, Cost Savings economics, Diabetic Retinopathy drug therapy, Diabetic Retinopathy economics, Drug Costs statistics & numerical data, Drug Substitution economics, Macular Degeneration drug therapy, Macular Degeneration economics, Macular Edema drug therapy, Macular Edema economics, Medicare Part B economics
Abstract

The biologic drugs bevacizumab and ranibizumab have revolutionized treatment of diabetic macular edema and neovascular age-related macular degeneration, leading causes of blindness. Ophthalmologic use of these drugs has increased and now accounts for roughly one-sixth of the Medicare Part B drug budget. The two drugs have similar efficacy and potentially minor differences in adverse-event rates; however, at $2,023 per dose, ranibizumab costs forty times more than bevacizumab. Using modeling methods, we predict ten-year (2010-20) population-level costs and health benefits of using bevacizumab and ranibizumab. Our results show that if all patients were treated with the less expensive bevacizumab instead of current usage patterns, savings would amount to $18 billion for Medicare Part B and nearly $5 billion for patients. With an additional $6 billion savings in other health care expenses, the total savings would be almost $29 billion. Altering patterns of use with these therapies by encouraging bevacizumab use and hastening approval of biosimilar therapies would dramatically reduce spending without substantially affecting patient outcomes., (Project HOPE—The People-to-People Health Foundation, Inc.)

Published
2014
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