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2. Three cases of acute venous thromboembolism in females following vaccination for COVID-19
- Author
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Andraska, E.A., Kulkarni, R., Chaudhary, M., and Sachdev, U.
- Subjects
pulmonary embolism ,COVID-19 ,Article ,Venous thromboembolism ,deep venous thrombosis - Abstract
Since December 2020, four vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and three have been approved for immediate use in the United States. Two are mRNA vaccines, while one uses a viral vector mechanism. There are reports of thrombotic complications following vaccine administration, which are primarily cerebral sinus thromboses following administration of the viral vector vaccines. Here, we are the first to report venous thrombotic complications within days of administration of the mRNA-1273 (Moderna) vaccine. We present a series of three women who developed venous thromboembolism (VTE) following mRNA-1273 vaccination at a single healthcare system.
- Published
- 2021
3. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
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Y, Oshima, S, Rong, Y, Sluimer, JC, Stallings, CL, and Tong, C-K
- Abstract
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
- Published
- 2021
4. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).
- Author
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Quadrilatero J., Walker D.W., Walker M.J., Walker S.A., Walter J., Wandosell F.G., Wang B., Wang C., Wang C.-Y., Wang D., Wang F., Wang G., Wang H., Wang H.-G., Wang J., Wang K., Wang L., Wang M.H., Wang M., Wang N., Wang P., Wang Q.J., Wang Q., Wang Q.K., Wang Q.A., Wang W.-T., Wang W., Wang X., Wang Y.-Y., Wang Y., Wang Z., Warnes G., Warnsmann V., Watada H., Watanabe E., Watchon M., Wawrzynska A., Weaver T.E., Wegrzyn G., Wehman A.M., Wei H., Wei L., Wei T., Wei Y., Weiergraber O.H., Weihl C.C., Weindl G., Weiskirchen R., Wells A., Wen R.H., Wen X., Werner A., Weykopf B., Wheatley S.P., W... [Ovid has truncated this field to avoid Excel character limitations], Klionsky D.J., Abdel-Aziz A.K., Abdelfatah S., Abdellatif M., Abdoli A., Abel S., Abeliovich H., Abildgaard M.H., Abudu Y.P., Acevedo-Arozena A., Adamopoulos I.E., Adeli K., Adolph T.E., Adornetto A., Aflaki E., Agam G., Agarwal A., Aggarwal B.B., Agnello M., Agostinis P., Agrewala J.N., Agrotis A., Aguilar P.V., Ahmad S.T., Ahmed Z.M., Ahumada-Castro U., Aits S., Aizawa S., Akkoc Y., Akoumianaki T., Akpinar H.A., Al-Abd A.M., Al-Akra L., Al-Gharaibeh A., Alaoui-Jamali M.A., Alberti S., Alcocer-Gomez E., Alessandri C., Ali M., Alim Al-Bari M.A., Aliwaini S., Alizadeh J., Almacellas E., Almasan A., Alonso A., Alonso G.D., Altan-Bonnet N., Altieri D.C., Alvarez E.M.C., Alves S., Alves da Costa C., Alzaharna M.M., Amadio M., Amantini C., Amaral C., Ambrosio S., Amer A.O., Ammanathan V., An Z., Andersen S.U., Andrabi S.A., Andrade-Silva M., Andres A.M., Angelini S., Ann D., Anozie U.C., Ansari M.Y., Antas P., Antebi A., 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C., Huang C., Huang H., Huang K., Huang M.L.H., Huang R., Huang S., Huang T., Huang X., Huang Y.J., Huber T.B., Hubert V., Hubner C.A., Hughes S.M., Hughes W.E., Humbert M., Hummer G., Hurley J.H., Hussain S., Hussey P.J., Hutabarat M., Hwang H.-Y., Hwang S., Ieni A., Ikeda F., Imagawa Y., Imai Y., Imbriano C., Imoto M., Inman D.M., Inoki K., Iovanna J., Iozzo R.V., Ippolito G., Irazoqui J.E., Iribarren P., Ishaq M., Ishikawa M., Ishimwe N., Isidoro C., Ismail N., Issazadeh-Navikas S., Itakura E., Ito D., Ivankovic D., Ivanova S., Iyer A.K.V., Izquierdo J.M., Izumi M., Jaattela M., Jabir M.S., Jackson W.T., Jacobo-Herrera N., Jacomin A.-C., Jacquin E., Jadiya P., Jaeschke H., Jagannath C., Jakobi A.J., Jakobsson J., Janji B., Jansen-Durr P., Jansson P.J., Jantsch J., Januszewski S., Jassey A., Jean S., Jeltsch-David H., Jendelova P., Jenny A., Jensen T.E., Jessen N., Jewell J.L., Ji J., Jia L., Jia R., Jiang L., Jiang Q., Jiang R., Jiang T., Jiang X., Jiang Y., Jimenez-Sanchez M., Jin E.-J., Jin F., Jin H., Jin L., Jin M., Jin S., Jo E.-K., Joffre C., Johansen T., Johnson G.V.W., Johnston S.A., Jokitalo E., Jolly M.K., Joosten L.A.B., Jordan J., Joseph B., Ju D., Ju J.-S., Ju J., Juarez E., Judith D., Juhasz G., Jun Y., Jung C.H., Jung S.-C., Jung Y.K., Jungbluth H., Jungverdorben J., Just S., Kaarniranta K., Kaasik A., Kabuta T., Kaganovich D., Kahana A., Kain R., Kajimura S., Kalamvoki M., Kalia M., Kalinowski D.S., Kaludercic N., Kalvari I., Kaminska J., Kaminskyy V.O., Kanamori H., Kanasaki K., Kang C., Kang R., Kang S.S., Kaniyappan S., Kanki T., Kanneganti T.-D., Kanthasamy A.G., Kanthasamy A., Kantorow M., Kapuy O., Karamouzis M.V., Karim M.R., Karmakar P., Katare R.G., Kato M., Kaufmann S.H.E., Kauppinen A., Kaushal G.P., Kaushik S., Kawasaki K., Kazan K., Ke P.-Y., Keating D.J., Keber U., Kehrl J.H., Keller K.E., Keller C.W., Kemper J.K., Kenific C.M., Kepp O., Kermorgant S., Kern A., Ketteler R., Keulers T.G., Khalfin B., Khalil H., Khambu B., Khan S.Y., Khandelwal V.K.M., Khandia R., Kho W., Khobrekar N.V., Khuansuwan S., Khundadze M., Killackey S.A., Kim D., Kim D.R., Kim D.-H., Kim D.-E., Kim E.Y., Kim E.-K., Kim H.-R., Kim H.-S., Hyung-Ryong Kim, Kim J.K., Kim J.-H., Kim J., Kim J.H., Kim K.I., Kim P.K., Kim S.-J., Kimball S.R., Kimchi A., Kimmelman A.C., Kimura T., King M.A., Kinghorn K.J., Kinsey C.G., Kirkin V., Kirshenbaum L.A., Kiselev S.L., Kishi S., Kitamoto K., Kitaoka Y., Kitazato K., Kitsis R.N., Kittler J.T., Kjaerulff O., Klein P.S., Klopstock T., Klucken J., Knaevelsrud H., Knorr R.L., Ko B.C.B., Ko F., Ko J.-L., Kobayashi H., Kobayashi S., Koch I., Koch J.C., Koenig U., Kogel D., Koh Y.H., Koike M., Kohlwein S.D., Kocaturk N.M., Komatsu M., Konig J., Kono T., Kopp B.T., Korcsmaros T., Korkmaz G., Korolchuk V.I., Korsnes M.S., Koskela A., Kota J., Kotake Y., Kotler M.L., Kou Y., Koukourakis M.I., Koustas E., Kovacs A.L., Kovacs T., Koya D., Kozako T., Kraft C., Krainc D., Kramer H., Krasnodembskaya A.D., Kretz-Remy C., Kroemer G., Ktistakis N.T., Kuchitsu K., Kuenen S., Kuerschner L., Kukar T., Kumar A., Kumar D., Kumar S., Kume S., Kumsta C., Kundu C.N., Kundu M., Kunnumakkara A.B., Kurgan L., Kutateladze T.G., Kutlu O., Kwak S., Kwon H.J., Kwon T.K., Kwon Y.T., Kyrmizi I., La Spada A., Labonte P., Ladoire S., Laface I., Lafont F., Lagace D.C., Lahiri V., Lai Z., Laird A.S., Lakkaraju A., Lamark T., Lan S.-H., Landajuela A., Lane D.J.R., Lane J.D., Lang C.H., Lange C., Langel U., Langer R., Lapaquette P., Laporte J., LaRusso N.F., Lastres-Becker I., Lau W.C.Y., Laurie G.W., Lavandero S., Law B.Y.K., Law H.K.-W., Layfield R., Le W., Le Stunff H., Leary A.Y., Lebrun J.-J., Leck L.Y.W., Leduc-Gaudet J.-P., Lee C., Lee C.-P., Lee D.-H., Lee E.B., Lee E.F., Lee G.M., Lee H.-J., Lee H.K., Lee J.M., Lee J.S., Lee J.-A., Lee J.-Y., Lee J.H., Lee M., Lee M.G., Lee M.J., Lee M.-S., Lee S.-J., Lee S.Y., Lee S.B., Lee W.H., Lee Y.-R., Lee Y.-H., Lee Y., Lefebvre C., Legouis R., Lei Y.L., Lei Y., Leikin S., Leitinger G., Lemus L., Leng S., Lenoir O., Lenz G., Lenz H.J., Lenzi P., Leon Y., Leopoldino A.M., Leschczyk C., Leskela S., Letellier E., Leung C.-T., Leung P.S., Leventhal J.S., Levine B., Lewis P.A., Ley K., Li B., Li D.-Q., Li J., Li K., Li L., Li M., Li P.-L., Li M.-Q., Li Q., Li S., Li T., Li W., Li X., Li Y.-P., Li Y., Lian J., Liang C., Liang Q., Liang W., Liang Y., Liao G., Liao L., Liao M., Liao Y.-F., Librizzi M., Lie P.P.Y., Lilly M.A., Lim H.J., Lima T.R.R., Limana F., Lin C., Lin C.-W., Lin D.-S., Lin F.-C., Lin J.D., Lin K.M., Lin K.-H., Lin L.-T., Lin P.-H., Lin Q., Lin S., Lin S.-J., Lin W., Lin X., Lin Y.-X., Lin Y.-S., Linden R., Lindner P., Ling S.-C., Lingor P., Linnemann A.K., Liou Y.-C., Lipinski M.M., Lipovsek S., Lira V.A., Lisiak N., Liton P.B., Liu C., Liu C.-H., Liu C.-F., Liu C.H., Liu F., Liu H.-S., Liu H.-F., Liu H., Liu J., Liu L., Liu M., Liu Q., Liu W., Liu X.-H., Liu X., Liu Y., Livingston J.A., Lizard G., Lizcano J.M., Ljubojevic-Holzer S., LLeonart 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[Ovid has truncated this field to avoid Excel character limitations], Klionsky D.J., Abdel-Aziz A.K., Abdelfatah S., Abdellatif M., Abdoli A., Abel S., Abeliovich H., Abildgaard M.H., Abudu Y.P., Acevedo-Arozena A., Adamopoulos I.E., Adeli K., Adolph T.E., Adornetto A., Aflaki E., Agam G., Agarwal A., Aggarwal B.B., Agnello M., Agostinis P., Agrewala J.N., Agrotis A., Aguilar P.V., Ahmad S.T., Ahmed Z.M., Ahumada-Castro U., Aits S., Aizawa S., Akkoc Y., Akoumianaki T., Akpinar H.A., Al-Abd A.M., Al-Akra L., Al-Gharaibeh A., Alaoui-Jamali M.A., Alberti S., Alcocer-Gomez E., Alessandri C., Ali M., Alim Al-Bari M.A., Aliwaini S., Alizadeh J., Almacellas E., Almasan A., Alonso A., Alonso G.D., Altan-Bonnet N., Altieri D.C., Alvarez E.M.C., Alves S., Alves da Costa C., Alzaharna M.M., Amadio M., Amantini C., Amaral C., Ambrosio S., Amer A.O., Ammanathan V., An Z., Andersen S.U., Andrabi S.A., Andrade-Silva M., Andres A.M., Angelini S., Ann D., Anozie U.C., Ansari M.Y., Antas P., Antebi A., 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C., Huang C., Huang H., Huang K., Huang M.L.H., Huang R., Huang S., Huang T., Huang X., Huang Y.J., Huber T.B., Hubert V., Hubner C.A., Hughes S.M., Hughes W.E., Humbert M., Hummer G., Hurley J.H., Hussain S., Hussey P.J., Hutabarat M., Hwang H.-Y., Hwang S., Ieni A., Ikeda F., Imagawa Y., Imai Y., Imbriano C., Imoto M., Inman D.M., Inoki K., Iovanna J., Iozzo R.V., Ippolito G., Irazoqui J.E., Iribarren P., Ishaq M., Ishikawa M., Ishimwe N., Isidoro C., Ismail N., Issazadeh-Navikas S., Itakura E., Ito D., Ivankovic D., Ivanova S., Iyer A.K.V., Izquierdo J.M., Izumi M., Jaattela M., Jabir M.S., Jackson W.T., Jacobo-Herrera N., Jacomin A.-C., Jacquin E., Jadiya P., Jaeschke H., Jagannath C., Jakobi A.J., Jakobsson J., Janji B., Jansen-Durr P., Jansson P.J., Jantsch J., Januszewski S., Jassey A., Jean S., Jeltsch-David H., Jendelova P., Jenny A., Jensen T.E., Jessen N., Jewell J.L., Ji J., Jia L., Jia R., Jiang L., Jiang Q., Jiang R., Jiang T., Jiang X., Jiang Y., Jimenez-Sanchez M., Jin E.-J., Jin F., Jin H., Jin L., Jin M., Jin S., Jo E.-K., Joffre C., Johansen T., Johnson G.V.W., Johnston S.A., Jokitalo E., Jolly M.K., Joosten L.A.B., Jordan J., Joseph B., Ju D., Ju J.-S., Ju J., Juarez E., Judith D., Juhasz G., Jun Y., Jung C.H., Jung S.-C., Jung Y.K., Jungbluth H., Jungverdorben J., Just S., Kaarniranta K., Kaasik A., Kabuta T., Kaganovich D., Kahana A., Kain R., Kajimura S., Kalamvoki M., Kalia M., Kalinowski D.S., Kaludercic N., Kalvari I., Kaminska J., Kaminskyy V.O., Kanamori H., Kanasaki K., Kang C., Kang R., Kang S.S., Kaniyappan S., Kanki T., Kanneganti T.-D., Kanthasamy A.G., Kanthasamy A., Kantorow M., Kapuy O., Karamouzis M.V., Karim M.R., Karmakar P., Katare R.G., Kato M., Kaufmann S.H.E., Kauppinen A., Kaushal G.P., Kaushik S., Kawasaki K., Kazan K., Ke P.-Y., Keating D.J., Keber U., Kehrl J.H., Keller K.E., Keller C.W., Kemper J.K., Kenific C.M., Kepp O., Kermorgant S., Kern A., Ketteler R., Keulers T.G., Khalfin B., Khalil H., Khambu B., Khan S.Y., Khandelwal V.K.M., Khandia R., Kho W., Khobrekar N.V., Khuansuwan S., Khundadze M., Killackey S.A., Kim D., Kim D.R., Kim D.-H., Kim D.-E., Kim E.Y., Kim E.-K., Kim H.-R., Kim H.-S., Hyung-Ryong Kim, Kim J.K., Kim J.-H., Kim J., Kim J.H., Kim K.I., Kim P.K., Kim S.-J., Kimball S.R., Kimchi A., Kimmelman A.C., Kimura T., King M.A., Kinghorn K.J., Kinsey C.G., Kirkin V., Kirshenbaum L.A., Kiselev S.L., Kishi S., Kitamoto K., Kitaoka Y., Kitazato K., Kitsis R.N., Kittler J.T., Kjaerulff O., Klein P.S., Klopstock T., Klucken J., Knaevelsrud H., Knorr R.L., Ko B.C.B., Ko F., Ko J.-L., Kobayashi H., Kobayashi S., Koch I., Koch J.C., Koenig U., Kogel D., Koh Y.H., Koike M., Kohlwein S.D., Kocaturk N.M., Komatsu M., Konig J., Kono T., Kopp B.T., Korcsmaros T., Korkmaz G., Korolchuk V.I., Korsnes M.S., Koskela A., Kota J., Kotake Y., Kotler M.L., Kou Y., Koukourakis M.I., Koustas E., Kovacs A.L., Kovacs T., Koya D., Kozako T., Kraft C., Krainc D., Kramer H., Krasnodembskaya A.D., Kretz-Remy C., Kroemer G., Ktistakis N.T., Kuchitsu K., Kuenen S., Kuerschner L., Kukar T., Kumar A., Kumar D., Kumar S., Kume S., Kumsta C., Kundu C.N., Kundu M., Kunnumakkara A.B., Kurgan L., Kutateladze T.G., Kutlu O., Kwak S., Kwon H.J., Kwon T.K., Kwon Y.T., Kyrmizi I., La Spada A., Labonte P., Ladoire S., Laface I., Lafont F., Lagace D.C., Lahiri V., Lai Z., Laird A.S., Lakkaraju A., Lamark T., Lan S.-H., Landajuela A., Lane D.J.R., Lane J.D., Lang C.H., Lange C., Langel U., Langer R., Lapaquette P., Laporte J., LaRusso N.F., Lastres-Becker I., Lau W.C.Y., Laurie G.W., Lavandero S., Law B.Y.K., Law H.K.-W., Layfield R., Le W., Le Stunff H., Leary A.Y., Lebrun J.-J., Leck L.Y.W., Leduc-Gaudet J.-P., Lee C., Lee C.-P., Lee D.-H., Lee E.B., Lee E.F., Lee G.M., Lee H.-J., Lee H.K., Lee J.M., Lee J.S., Lee J.-A., Lee J.-Y., Lee J.H., Lee M., Lee M.G., Lee M.J., Lee M.-S., Lee S.-J., Lee S.Y., Lee S.B., Lee W.H., Lee Y.-R., Lee Y.-H., Lee Y., Lefebvre C., Legouis R., Lei Y.L., Lei Y., Leikin S., Leitinger G., Lemus L., Leng S., Lenoir O., Lenz G., Lenz H.J., Lenzi P., Leon Y., Leopoldino A.M., Leschczyk C., Leskela S., Letellier E., Leung C.-T., Leung P.S., Leventhal J.S., Levine B., Lewis P.A., Ley K., Li B., Li D.-Q., Li J., Li K., Li L., Li M., Li P.-L., Li M.-Q., Li Q., Li S., Li T., Li W., Li X., Li Y.-P., Li Y., Lian J., Liang C., Liang Q., Liang W., Liang Y., Liao G., Liao L., Liao M., Liao Y.-F., Librizzi M., Lie P.P.Y., Lilly M.A., Lim H.J., Lima T.R.R., Limana F., Lin C., Lin C.-W., Lin D.-S., Lin F.-C., Lin J.D., Lin K.M., Lin K.-H., Lin L.-T., Lin P.-H., Lin Q., Lin S., Lin S.-J., Lin W., Lin X., Lin Y.-X., Lin Y.-S., Linden R., Lindner P., Ling S.-C., Lingor P., Linnemann A.K., Liou Y.-C., Lipinski M.M., Lipovsek S., Lira V.A., Lisiak N., Liton P.B., Liu C., Liu C.-H., Liu C.-F., Liu C.H., Liu F., Liu H.-S., Liu H.-F., Liu H., Liu J., Liu L., Liu M., Liu Q., Liu W., Liu X.-H., Liu X., Liu Y., Livingston J.A., Lizard G., Lizcano J.M., Ljubojevic-Holzer S., LLeonart 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Viret C., Viscomi M.T., Visnjic D., Vitale I., Vocadlo D.J., Voitsekhovskaja O.V., Volonte C., Volta M., Vomero M., Von Haefen C., Vooijs M.A., Voos W., Vucicevic L., Wade-Martins R., Waguri S., Waite K.A., and Wakatsuki S.
- Abstract
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.Copyright © 2020 Informa UK Limited, trading as Taylor & Francis Group.
- Published
- 2021
5. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.
- Author
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C., Johansen T., Johnson G.V.W., Johnston S.A., Jokitalo E., Jolly M.K., Joosten L.A.B., Jordan J., Joseph B., Ju D., Ju J.-S., Ju J., Juarez E., Judith D., Juhasz G., Jun Y., Jung C.H., Jung S.-C., Jung Y.K., Jungbluth H., Jungverdorben J., Just S., Kaarniranta K., Kaasik A., Kabuta T., Kaganovich D., Kahana A., Kain R., Kajimura S., Kalamvoki M., Kalia M., Kalinowski D.S., Kaludercic N., Kalvari I., Kaminska J., Kaminskyy V.O., Kanamori H., Kanasaki K., Kang C., Kang R., Kang S.S., Kaniyappan S., Kanki T., Kanneganti T.-D., Kanthasamy A.G., Kanthasamy A., Kantorow M., Kapuy O., Karamouzis M.V., Karim M.R., Karmakar P., Katare R.G., Kato M., Kaufmann S.H.E., Kauppinen A., Kaushal G.P., Kaushik S., Kawasaki K., Kazan K., Ke P.-Y., Keating D.J., Keber U., Kehrl J.H., Keller K.E., Keller C.W., Kemper J.K., Kenific C.M., Kepp O., Kermorgant S., Kern A., Ketteler R., Keulers T.G., Khalfin B., Khalil H., Khambu B., Khan S.Y., Khandelwal V.K.M., Khandia R., Kho W., Khobrekar N.V., Khuansuwan 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Lenzi P., Leon Y., Leopoldino A.M., Leschczyk C., Leskela S., Letellier E., Leung C.-T., Leung P.S., Leventhal J.S., Levine B., Lewis P.A., Ley K., Li B., Li D.-Q., Li J., Li K., Li L., Li M., Li P.-L., Li M.-Q., Li Q., Li S., Li T., Li W., Li X., Li Y.-P., Li Y., Lian J., Liang C., Liang Q., Liang W., Liang Y., Liao G., Liao L., Liao M., Liao Y.-F., Librizzi M., Lie P.P.Y., Lilly M.A., Lim H.J., Lima T.R.R., Limana F., Lin C., Lin C.-W., Lin D.-S., Lin F.-C., Lin J.D., Lin K.M., Lin K.-H., Lin L.-T., Lin P.-H., Lin Q., Lin S., Lin S.-J., Lin W., Lin X., Lin Y.-X., Lin Y.-S., Linden R., Lindner P., Ling S.-C., Lingor P., Linnemann A.K., Liou Y.-C., Lipinski M.M., Lipovsek S., Lira V.A., Lisiak N., Liton P.B., Liu C., Liu C.-H., Liu C.-F., Liu C.H., Liu F., Liu H.-S., Liu H.-F., Liu H., Liu J., Liu L., Liu M., Liu Q., Liu W., Liu X.-H., Liu X., Liu Y., Livingston J.A., Lizard G., Lizcano J.M., Ljubojevic-Holzer S., LLeonart M.E., Llobet-Navas D., Llorente A., Lo C.H., Lobato-Marquez D., 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[Ovid has truncated this field to avoid Excel character limitations], Klionsky D.J., Abdel-Aziz A.K., Abdelfatah S., Abdellatif M., Abdoli A., Abel S., Abeliovich H., Abildgaard M.H., Abudu Y.P., Acevedo-Arozena A., Adamopoulos I.E., Adeli K., Adolph T.E., Adornetto A., Aflaki E., Agam G., Agarwal A., Aggarwal B.B., Agnello M., Agostinis P., Agrewala J.N., Agrotis A., Aguilar P.V., Ahmad S.T., Ahmed Z.M., Ahumada-Castro U., Aits S., Aizawa S., Akkoc Y., Akoumianaki T., Akpinar H.A., Al-Abd A.M., Al-Akra L., Al-Gharaibeh A., Alaoui-Jamali M.A., Alberti S., Alcocer-Gomez E., Alessandri C., Ali M., Alim Al-Bari M.A., Aliwaini S., Alizadeh J., Almacellas E., Almasan A., Alonso A., Alonso G.D., Altan-Bonnet N., Altieri D.C., Alvarez E.M.C., Alves S., Alves da Costa C., Alzaharna M.M., Amadio M., Amantini C., Amaral C., Ambrosio S., Amer A.O., Ammanathan V., An Z., Andersen S.U., Andrabi S.A., Andrade-Silva M., Andres A.M., Angelini S., Ann D., Anozie U.C., Ansari M.Y., Antas P., Antebi A., 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Khandelwal V.K.M., Khandia R., Kho W., Khobrekar N.V., Khuansuwan S., Khundadze M., Killackey S.A., Kim D., Kim D.R., Kim D.-H., Kim D.-E., Kim E.Y., Kim E.-K., Kim H.-R., Kim H.-S., Hyung-Ryong Kim, Kim J.K., Kim J.-H., Kim J., Kim J.H., Kim K.I., Kim P.K., Kim S.-J., Kimball S.R., Kimchi A., Kimmelman A.C., Kimura T., King M.A., Kinghorn K.J., Kinsey C.G., Kirkin V., Kirshenbaum L.A., Kiselev S.L., Kishi S., Kitamoto K., Kitaoka Y., Kitazato K., Kitsis R.N., Kittler J.T., Kjaerulff O., Klein P.S., Klopstock T., Klucken J., Knaevelsrud H., Knorr R.L., Ko B.C.B., Ko F., Ko J.-L., Kobayashi H., Kobayashi S., Koch I., Koch J.C., Koenig U., Kogel D., Koh Y.H., Koike M., Kohlwein S.D., Kocaturk N.M., Komatsu M., Konig J., Kono T., Kopp B.T., Korcsmaros T., Korkmaz G., Korolchuk V.I., Korsnes M.S., Koskela A., Kota J., Kotake Y., Kotler M.L., Kou Y., Koukourakis M.I., Koustas E., Kovacs A.L., Kovacs T., Koya D., Kozako T., Kraft C., Krainc D., Kramer H., Krasnodembskaya A.D., Kretz-Remy C., 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Leitinger G., Lemus L., Leng S., Lenoir O., Lenz G., Lenz H.J., Lenzi P., Leon Y., Leopoldino A.M., Leschczyk C., Leskela S., Letellier E., Leung C.-T., Leung P.S., Leventhal J.S., Levine B., Lewis P.A., Ley K., Li B., Li D.-Q., Li J., Li K., Li L., Li M., Li P.-L., Li M.-Q., Li Q., Li S., Li T., Li W., Li X., Li Y.-P., Li Y., Lian J., Liang C., Liang Q., Liang W., Liang Y., Liao G., Liao L., Liao M., Liao Y.-F., Librizzi M., Lie P.P.Y., Lilly M.A., Lim H.J., Lima T.R.R., Limana F., Lin C., Lin C.-W., Lin D.-S., Lin F.-C., Lin J.D., Lin K.M., Lin K.-H., Lin L.-T., Lin P.-H., Lin Q., Lin S., Lin S.-J., Lin W., Lin X., Lin Y.-X., Lin Y.-S., Linden R., Lindner P., Ling S.-C., Lingor P., Linnemann A.K., Liou Y.-C., Lipinski M.M., Lipovsek S., Lira V.A., Lisiak N., Liton P.B., Liu C., Liu C.-H., Liu C.-F., Liu C.H., Liu F., Liu H.-S., Liu H.-F., Liu H., Liu J., Liu L., Liu M., Liu Q., Liu W., Liu X.-H., Liu X., Liu Y., Livingston J.A., Lizard G., Lizcano J.M., Ljubojevic-Holzer S., LLeonart 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O., Vindis C., Viret C., Viscomi M.T., Visnjic D., Vitale I., Vocadlo D.J., Voitsekhovskaja O.V., Volonte C., Volta M., Vomero M., Von Haefen C., Vooijs M.A., Voos W., Vucicevic L., Wade-Martins R., Waguri S., Waite K.A., Wakatsuki S., Walker D.W., Walker M.J., Walker S.A., Walter J., Wandosell F.G., Wang B., Wang C., Wang C.-Y., Wang D., Wang F., Wang G., Wang H., Wang H.-G., Wang J., Wang K., Wang L., Wang M.H., Wang M., Wang N., Wang P., Wang Q.J., Wang Q., Wang Q.K., Wang Q.A., Wang W.-T., Wang W., Wang X., Wang Y.-Y., Wang Y., Wang Z., Warnes G., Warnsmann V., Watada H., Watanabe E., Watchon M., Wawrzynska A., Weaver T.E., Wegrzyn G., Wehman A.M., Wei H., Wei L., Wei T., Wei Y., Weiergraber O.H., Weihl C.C., Weindl G., Weiskirchen R., Wells A., Wen R.H., Wen X., Werner A., Weykopf B., Wheatley S.P., and W... [Ovid has truncated this field to avoid Excel character limitations]
- Abstract
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.Copyright © 2020 Informa UK Limited, trading as Taylor & Francis Group.
- Published
- 2021
6. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
- Author
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Werner, Brand-Saberi, Beate, Dong, X Charlie, Kenchappa, Chandra Shekar, Li, Zuguo, Lin, Yong, Oshima, Shigeru, Rong, Yueguang, Sluimer, Judith C, Stallings, Christina L, and Tong, Chun-Kit
- Abstract
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
- Published
- 2021
7. Autologous Alternative Veins Do Not Provide Better Mid-term Outcomes than Prosthetic Conduits for Below Knee Bypass When Great Saphenous Vein is Unavailable
- Author
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Avgerinos, E.D., primary, Naddaf, A., additional, Sachdev, U., additional, Doucet, D., additional, Mohapatra, A., additional, Leers, S.A., additional, Chaer, R.A., additional, and Makaroun, M.S., additional
- Published
- 2014
- Full Text
- View/download PDF
8. Reduced Early Inflammation in Response to Hindlimb Ischemia in P2Y2 Receptor Knockout Mice – Potential Mechanism of Reduced Arteriogenesis
- Author
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Shukla, A.J., primary, McEnaney, R., additional, Sachdev, U., additional, and Tzeng, E., additional
- Published
- 2014
- Full Text
- View/download PDF
9. Modulation of Autophagy by Chloroquine Affects HMGB1 Expression and Release in Ischemic Skeletal Muscle
- Author
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Xu, J., primary, Cui, X., additional, Loughran, P., additional, Tzeng, E., additional, and Sachdev, U., additional
- Published
- 2014
- Full Text
- View/download PDF
10. Differing Effects of TLR2 and TLR4 Antagonism in Endothelial Cell Angiogenic Behavior: Implications for Angiogenesis After Hindlimb Ischemia
- Author
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Sachdev, U., primary, McEnaney, R., additional, Cui, X., additional, and Tzeng, E., additional
- Published
- 2012
- Full Text
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11. Requirement For HMGB-1 And Autophagic Signaling In Endothelial Angiogenic Behavior
- Author
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McEnaney, R., primary, Cui, X., additional, Tzeng, E., additional, and Sachdev, U., additional
- Published
- 2011
- Full Text
- View/download PDF
12. TLR4 and RAGE Function Are Not Essential for Angiogenesis in a Model of Hind-Limb Ischemia
- Author
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Sachdev, U., primary, Cui, X., additional, Chen, D., additional, Wang, T., additional, and Tzeng, E., additional
- Published
- 2010
- Full Text
- View/download PDF
13. Metastatic uterine leiomyosarcoma presenting as a primary sarcoma of the parotid gland.
- Author
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Saiz, A D, Sachdev, U, Brodman, M L, and Deligdisch, L
- Published
- 1998
14. Autophagy
- Author
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Razaul, Karmakar, Parimal, Katare, Rajesh G., Kato, Masaru, Kaufmann, Stefan H.E., Kauppinen, Anu, Kaushal, Gur P., Kaushik, Susmita, Kawasaki, Kiyoshi, Kazan, Kemal, Ke, Po-Yuan, Keating, Damien J., Keber, Ursula, Kehrl, John H., Keller, Kate E., Keller, Christian W., Kemper, Jongsook Kim, Kenific, Candia M., Kepp, Oliver, Kermorgant, Stephanie, Kern, Andreas, Ketteler, Robin, Keulers, Tom G., Khalfin, Boris, Khalil, Hany, Khambu, Bilon, Khan, Shahid Y., Khandelwal, Vinoth Kumar Megraj, Khandia, Rekha, Kho, Widuri, Khobrekar, Noopur V., Khuansuwan, Sataree, Khundadze, Mukhran, Killackey, Samuel A., Kim, Dasol, Kim, Deok Ryong, Kim, Do-Hyung, Kim, Dong-Eun, Kim, Eun Young, Kim, Eun-Kyoung, Kim, Hak-Rim, Kim, Hee-Sik, Hyung-Ryong Kim, Kim, Jeong Hun, Kim, Jin Kyung, Kim, Jin-Hoi, Kim, Joungmok, Kim, Ju Hwan, Kim, Keun Il, Kim, Peter K., Kim, Seong-Jun, Kimball, Scot R., Kimchi, Adi, Kimmelman, Alec C., Kimura, Tomonori, King, Matthew A., Kinghorn, Kerri J., Kinsey, Conan G., Kirkin, Vladimir, Kirshenbaum, Lorrie A., Kiselev, Sergey L., Kishi, Shuji, Kitamoto, Katsuhiko, Kitaoka, Yasushi, Kitazato, Kaio, Kitsis, Richard N., Kittler, Josef T., Kjaerulff, Ole, Klein, Peter S., Klopstock, Thomas, Klucken, Jochen, Knævelsrud, Helene, Knorr, Roland L., Ko, Ben C.B., Ko, Fred, Ko, Jiunn-Liang, Kobayashi, Hotaka, Kobayashi, Satoru, Koch, Ina, Koch, Jan C., Koenig, Ulrich, Kögel, Donat, Koh, Young Ho, Koike, Masato, Kohlwein, Sepp D., Kocaturk, Nur M., Komatsu, Masaaki, König, Jeannette, Kono, Toru, Kopp, Benjamin T., Korcsmaros, Tamas, Korkmaz, Gözde, Korolchuk, Viktor I., Korsnes, Mónica Suárez, Koskela, Ali, Kota, Janaiah, Kotake, Yaichiro, Kotler, Monica L., Kou, Yanjun, Koukourakis, Michael I., Koustas, Evangelos, Kovacs, Attila L., Kovács, Tibor, Koya, Daisuke, Kozako, Tomohiro, Kraft, Claudine, Krainc, Dimitri, Krämer, Helmut, Krasnodembskaya, Anna D., Kretz-Remy, Carole, Kroemer, Guido, Ktistakis, Nicholas T., Kuchitsu, Kazuyuki, Kuenen, Sabine, Kuerschner, Lars, Kukar, Thomas, Kumar, Ajay, Kumar, Ashok, Kumar, Deepak, Kumar, Dhiraj, Kumar, Sharad, Kume, Shinji, Kumsta, Caroline, Kundu, Chanakya N., Kundu, Mondira, Kunnumakkara, Ajaikumar B., Kurgan, Lukasz, Kutateladze, Tatiana G., Kutlu, Ozlem, Kwak, SeongAe, Kwon, Ho Jeong, Kwon, Taeg Kyu, Kwon, Yong Tae, Kyrmizi, Irene, La Spada, Albert, Labonté, Patrick, Ladoire, Sylvain, Laface, Ilaria, Lafont, Frank, Lagace, Diane C., Lahiri, Vikramjit, Lai, Zhibing, Laird, Angela S., Lakkaraju, Aparna, Lamark, Trond, Lan, Sheng-Hui, Landajuela, Ane, Lane, Darius J. R., Lane, Jon D., Lang, Charles H., Lange, Carsten, Langel, Ülo, Langer, Rupert, Lapaquette, Pierre, Laporte, Jocelyn, LaRusso, Nicholas F., Lastres-Becker, Isabel, Lau, Wilson Chun Yu, Laurie, Gordon W., Lavandero, Sergio, Law, Betty Yuen Kwan, Law, Helen Ka-wai, Layfield, Rob, Le, Weidong, Le Stunff, Herve, Leary, Alexandre Y., Lebrun, Jean-Jacques, Leck, Lionel Y.W., Leduc-Gaudet, Jean-Philippe, Lee, Changwook, Lee, Chung-Pei, Lee, Da-Hye, Lee, Edward B., Lee, Erinna F., Lee, Gyun Min, Lee, He-Jin, Lee, Heung Kyu, Lee, Jae Man, Lee, Jason S., Lee, Jin-A, Lee, Joo-Yong, Lee, Jun Hee, Lee, Michael, Lee, Min Goo, Lee, Min Jae, Lee, Myung-Shik, Lee, Sang Yoon, Lee, Seung-Jae, Lee, Stella Y., Lee, Sung Bae, Lee, Won Hee, Lee, Ying-Ray, Lee, Yong-ho, Lee, Youngil, Lefebvre, Christophe, Legouis, Renaud, Lei, Yu L., Lei, Yuchen, Leikin, Sergey, Leitinger, Gerd, Lemus, Leticia, Leng, Shuilong, Lenoir, Olivia, Lenz, Guido, Lenz, Heinz Josef, Lenzi, Paola, León, Yolanda, Leopoldino, Andréia M., Leschczyk, Christoph, Leskelä, Stina, Letellier, Elisabeth, Leung, Chi-Ting, Leung, Po Sing, Leventhal, Jeremy S., Levine, Beth, Lewis, Patrick A., Ley, Klaus, Li, Bin, Li, Da-Qiang, Li, Jianming, Li, Jing, Li, Jiong, Li, Ke, Li, Liwu, Li, Mei, Li, Min, Li, Ming, Li, Mingchuan, Li, Pin-Lan, Li, Ming-Qing, Li, Qing, Li, Sheng, Li, Tiangang, Li, Wei, Li, Wenming, Li, Xue, Li, Yi-Ping, Li, Yuan, Li, Zhiqiang, Li, Zhiyong, Li, Zhiyuan, Lian, Jiqin, Liang, Chengyu, Liang, Qiangrong, Liang, Weicheng, Liang, Yongheng, Liang, YongTian, Liao, Guanghong, Liao, Lujian, Liao, Mingzhi, Liao, Yung-Feng, Librizzi, Mariangela, Lie, Pearl P. Y., Lilly, Mary A., Lim, Hyunjung J., Lima, Thania R.R., Limana, Federica, Lin, Chao, Lin, Chih-Wen, Lin, Dar-Shong, Lin, Fu-Cheng, Lin, Jiandie D., Lin, Kurt M., Lin, Kwang-Huei, Lin, Liang-Tzung, Lin, Pei-Hui, Lin, Qiong, Lin, Shaofeng, Lin, Su-Ju, Lin, Wenyu, Lin, Xueying, Lin, Yao-Xin, Lin, Yee-Shin, Linden, Rafael, Lindner, Paula, Ling, Shuo-Chien, Lingor, Paul, Linnemann, Amelia K., Liou, Yih-Cherng, Lipinski, Marta M., Lipovšek, Saška, Lira, Vitor A., Lisiak, Natalia, Liton, Paloma B., Liu, Chao, Liu, Ching-Hsuan, Liu, Chun-Feng, Liu, Cui Hua, Liu, Fang, Liu, Hao, Liu, Hsiao-Sheng, Liu, Hua-feng, Liu, Huifang, Liu, Jia, Liu, Jing, Liu, Julia, Liu, Leyuan, Liu, Longhua, Liu, Meilian, Liu, Qin, Liu, Wei, Liu, Wende, Liu, Xiao-Hong, Liu, Xiaodong, Liu, Xingguo, Liu, Xu, Liu, Xuedong, Liu, Yanfen, Liu, Yang, Liu, Yueyang, Liu, Yule, Livingston, J. Andrew, Lizard, Gerard, Lizcano, Jose M., Ljubojevic-Holzer, Senka, LLeonart, Matilde E., Llobet-Navàs, David, Llorente, Alicia, Lo, Chih Hung, Lobato-Márquez, Damián, Long, Qi, Long, Yun Chau, Loos, Ben, Loos, Julia A., López, Manuela G., López-Doménech, Guillermo, López-Guerrero, José Antonio, López-Jiménez, Ana T., López-Pérez, Óscar, López-Valero, Israel, Lorenowicz, Magdalena J., Lorente, Mar, Lorincz, Peter, Lossi, Laura, Lotersztajn, Sophie, Lovat, Penny E., Lovell, Jonathan F., Lovy, Alenka, Lőw, Péter, Lu, Guang, Lu, Haocheng, Lu, Jia-Hong, Lu, Jin-Jian, Lu, Mengji, Lu, Shuyan, Luciani, Alessandro, Lucocq, John M., Ludovico, Paula, Luftig, Micah A., Luhr, Morten, Luis-Ravelo, Diego, Lum, Julian J., Luna-Dulcey, Liany, Lund, Anders H., Lund, Viktor K., Lünemann, Jan D., Lüningschrör, Patrick, Luo, Honglin, Luo, Rongcan, Luo, Shouqing, Luo, Zhi, Luparello, Claudio, Lüscher, Bernhard, Luu, Luan, Lyakhovich, Alex, Lyamzaev, Konstantin G., Lystad, Alf Håkon, Lytvynchuk, Lyubomyr, Ma, Alvin C., Ma, Changle, Ma, Mengxiao, Ma, Ning-Fang, Ma, Quan-Hong, Ma, Xinliang, Ma, Yueyun, Ma, Zhenyi, MacDougald, Ormond A., Macian, Fernando, MacIntosh, Gustavo C., MacKeigan, Jeffrey P., Macleod, Kay F., Maday, Sandra, Madeo, Frank, Madesh, Muniswamy, Madl, Tobias, Madrigal-Matute, Julio, Maeda, Akiko, Maejima, Yasuhiro, Magarinos, Marta, Mahavadi, Poornima, Maiani, Emiliano, Maiese, Kenneth, Maiti, Panchanan, Maiuri, Maria Chiara, Majello, Barbara, Major, Michael B., Makareeva, Elena, Malik, Fayaz, Mallilankaraman, Karthik, Malorni, Walter, Maloyan, Alina, Mammadova, Najiba, Man, Gene Chi Wai, Manai, Federico, Mancias, Joseph D., Mandelkow, Eva-Maria, Mandell, Michael A., Manfredi, Angelo A., Manjili, Masoud H., Manjithaya, Ravi, Manque, Patricio, Manshian, Bella B., Manzano, Raquel, Manzoni, Claudia, Mao, Kai, Marchese, Cinzia, Marchetti, Sandrine, Marconi, Anna Maria, Marcucci, Fabrizio, Mardente, Stefania, Mareninova, Olga A., Margeta, Marta, Mari, Muriel, Marinelli, Sara, Marinelli, Oliviero, Mariño, Guillermo, Mariotto, Sofia, Marshall, Richard S., Marten, Mark R., Martens, Sascha, Martin, Alexandre P.J., Martin, Katie R., Martin, Sara, Martin, Shaun, Martín-Segura, Adrián, Martín-Acebes, Miguel A., Martin-Burriel, Inmaculada, Martin-Rincon, Marcos, Martin-Sanz, Paloma, Martina, José A., Martinet, Wim, Martinez, Aitor, Martinez, Ana, Martinez, Jennifer, Martinez Velazquez, Moises, Martinez-Lopez, Nuria, Martinez-Vicente, Marta, Martins, Daniel O., Martins, Joilson O., Martins, Waleska K., Martins-Marques, Tania, Marzetti, Emanuele, Masaldan, Shashank, Masclaux-Daubresse, Celine, Mashek, Douglas G., Massa, Valentina, Massieu, Lourdes, Masson, Glenn R., Masuelli, Laura, Masyuk, Anatoliy I., Masyuk, Tetyana V., Matarrese, Paola, Matheu, Ander, Matoba, Satoaki, Matsuzaki, Sachiko, Mattar, Pamela, Matte, Alessandro, Mattoscio, Domenico, Mauriz, José L., Mauthe, Mario, Mauvezin, Caroline, Maverakis, Emanual, Maycotte, Paola, Mayer, Johanna, Mazzoccoli, Gianluigi, Mazzoni, Cristina, Mazzulli, Joseph R., McCarty, Nami, McDonald, Christine, McGill, Mitchell R., McKenna, Sharon L., McLaughlin, BethAnn, McLoughlin, Fionn, McNiven, Mark A., McWilliams, Thomas G., Mechta-Grigoriou, Fatima, Medeiros, Tania Catarina, Medina, Diego L., Megeney, Lynn A., Megyeri, Klara, Mehrpour, Maryam, Mehta, Jawahar L., Meijer, Alfred J., Meijer, Annemarie H., Mejlvang, Jakob, Meléndez, Alicia, Melk, Annette, Memisoglu, Gonen, Mendes, Alexandrina F., Meng, Delong, Meng, Fei, Meng, Tian, Menna-Barreto, Rubem, Menon, Manoj B., Mercer, Carol, Mercier, Anne E., Mergny, Jean-Louis, Merighi, Adalberto, Merkley, Seth D., Merla, Giuseppe, Meske, Volker, Mestre, Ana Cecilia, Metur, Shree Padma, Meyer, Christian, Meyer, Hemmo, Mi, Wenyi, Mialet-Perez, Jeanne, Miao, Junying, Micale, Lucia, Miki, Yasuo, Milan, Enrico, Milczarek, Małgorzata, Miller, Dana L., Miller, Samuel I., Miller, Silke, Millward, Steven W., Milosevic, Ira, Minina, Elena A., Mirzaei, Hamed, Mirzaei, Hamid Reza, Mirzaei, Mehdi, Mishra, Amit, Mishra, Nandita, Mishra, Paras Kumar, Misirkic Marjanovic, Maja, Misasi, Roberta, Misra, Amit, Misso, Gabriella, Mitchell, Claire, Mitou, Geraldine, Miura, Tetsuji, Miyamoto, Shigeki, Miyazaki, Makoto, Miyazaki, Mitsunori, Miyazaki, Taiga, Miyazawa, Keisuke, Mizushima, Noboru, Mogensen, Trine H., Mograbi, Baharia, Mohammadinejad, Reza, Mohamud, Yasir, Mohanty, Abhishek, Mohapatra, Sipra, Möhlmann, Torsten, Mohmmed, Asif, Moles, Anna, Moley, Kelle H., Molinari, Maurizio, Mollace, Vincenzo, Møller, Andreas Buch, Mollereau, Bertrand, Mollinedo, Faustino, Montagna, Costanza, Monteiro, Mervyn J., Montella, Andrea, Montes, L. Ruth, Montico, Barbara, Mony, Vinod K., Monzio Compagnoni, Giacomo, Moore, Michael N., Moosavi, Mohammad A., Mora, Ana L., Mora, Marina, Morales-Alamo, David, Moratalla, Rosario, Moreira, Paula I., Morelli, Elena, Moreno, Sandra, Moreno-Blas, Daniel, Moresi, Viviana, Morga, Benjamin, Morgan, Alwena H., Morin, Fabrice, Morishita, Hideaki, Moritz, Orson L., Moriyama, Mariko, Moriyasu, Yuji, Morleo, Manuela, Morselli, Eugenia, Moruno-Manchon, Jose F., Moscat, Jorge, Mostowy, Serge, Motori, Elisa, Moura, Andrea Felinto, Moustaid-Moussa, Naima, Mrakovcic, Maria, Muciño-Hernández, Gabriel, Mukherjee, Anupam, Mukhopadhyay, Subhadip, Mulcahy Levy, Jean M., Mulero, Victoriano, Muller, Sylviane, Münch, Christian, Munjal, Ashok, Munoz-Canoves, Pura, Muñoz-Galdeano, Teresa, Münz, Christian, Murakawa, Tomokazu, Muratori, Claudia, Murphy, Brona M., Murphy, J. Patrick, Murthy, Aditya, Myöhänen, Timo T., Mysorekar, Indira U., Mytych, Jennifer, Nabavi, Seyed Mohammad, Nabissi, Massimo, Nagy, Péter, Nah, Jihoon, Nahimana, Aimable, Nakagawa, Ichiro, Nakamura, Ken, Nakatogawa, Hitoshi, Nandi, Shyam S., Nanjundan, Meera, Nanni, Monica, Napolitano, Gennaro, Nardacci, Roberta, Narita, Masashi, Nassif, Melissa, Nathan, Ilana, Natsumeda, Manabu, Naude, Ryno J., Naumann, Christin, Naveiras, Olaia, Navid, Fatemeh, Nawrocki, Steffan T., Nazarko, Taras Y., Nazio, Francesca, Negoita, Florentina, Neill, Thomas, Neisch, Amanda L., Neri, Luca M., Netea, Mihai G., Neubert, Patrick, Neufeld, Thomas P., Neumann, Dietbert, Neutzner, Albert, Newton, Phillip T., Ney, Paul A., Nezis, Ioannis P., Ng, Charlene C.W., Ng, Tzi Bun, Nguyen, Hang T. T., Nguyen, Long T., Ni, Hong-Min, Ní Cheallaigh, Clíona, Ni, Zhenhong, Nicolao, M. Celeste, Nicoli, Francesco, Nieto-Diaz, Manuel, Nilsson, Per, Ning, Shunbin, Niranjan, Rituraj, Nishimune, Hiroshi, Niso-Santano, Mireia, Nixon, Ralph A., Nobili, Annalisa, Nobrega, Clevio, Noda, Takeshi, Nogueira-Recalde, Uxía, Nolan, Trevor M., Nombela, Ivan, Novak, Ivana, Novoa, Beatriz, Nozawa, Takashi, Nukina, Nobuyuki, Nussbaum-Krammer, Carmen, Nylandsted, Jesper, O’Donovan, Tracey R., O’Leary, Seónadh M., O’Rourke, Eyleen J., O’Sullivan, Mary P., O’Sullivan, Timothy E., Oddo, Salvatore, Oehme, Ina, Ogawa, Michinaga, Ogier-Denis, Eric, Ogmundsdottir, Margret H., Ogretmen, Besim, Oh, Goo Taeg, Oh, Seon-Hee, Oh, Young J., Ohama, Takashi, Ohashi, Yohei, Ohmuraya, Masaki, Oikonomou, Vasileios, Ojha, Rani, Okamoto, Koji, Okazawa, Hitoshi, Oku, Masahide, Oliván, Sara, Oliveira, Jorge M. A., Ollmann, Michael, Olzmann, James A., Omari, Shakib, Omary, M. Bishr, Önal, Gizem, Ondrej, Martin, Ong, Sang-Bing, Ong, Sang-Ging, Onnis, Anna, Orellana, Juan A., Orellana-Muñoz, Sara, Ortega-Villaizan, Maria Del Mar, Ortiz-Gonzalez, Xilma R., Ortona, Elena, Osiewacz, Heinz D., Osman, Abdel-Hamid K., Osta, Rosario, Otegui, Marisa S., Otsu, Kinya, Ott, Christiane, Ottobrini, Luisa, Ou, Jing-hsiung James, Outeiro, Tiago F., Oynebraten, Inger, Ozturk, Melek, Pagès, Gilles, Pahari, Susanta, Pajares, Marta, Pajvani, Utpal B., Pal, Rituraj, Paladino, Simona, Pallet, Nicolas, Palmieri, Michela, Palmisano, Giuseppe, Palumbo, Camilla, Pampaloni, Francesco, Pan, Lifeng, Pan, Qingjun, Pan, Wenliang, Pan, Xin, Panasyuk, Ganna, Pandey, Rahul, Pandey, Udai B., Pandya, Vrajesh, Paneni, Francesco, Pang, Shirley Y., Panzarini, Elisa, Papademetrio, Daniela L., Papaleo, Elena, Papinski, Daniel, Papp, Diana, Park, Eun Chan, Park, Hwan Tae, Park, Ji-Man, Park, Jong-In, Park, Joon Tae, Park, Junsoo, Park, Sang Chul, Park, Sang-Youel, Parola, Abraham H., Parys, Jan B., Pasquier, Adrien, Pasquier, Benoit, Passos, João F., Pastore, Nunzia, Patel, Hemal H., Patschan, Daniel, Pattingre, Sophie, Pedraza-Alva, Gustavo, Pedraza-Chaverri, Jose, Pedrozo, Zully, Pei, Gang, Pei, Jianming, Peled-Zehavi, Hadas, Pellegrini, Joaquín M., Pelletier, Joffrey, Peñalva, Miguel A., Peng, Di, Peng, Ying, Penna, Fabio, Pennuto, Maria, Pentimalli, Francesca, Pereira, Cláudia MF, Pereira, Gustavo J.S., Pereira, Lilian C., Pereira de Almeida, Luis, Perera, Nirma D., Pérez-Lara, Ángel, Perez-Oliva, Ana B., Pérez-Pérez, María Esther, Periyasamy, Palsamy, Perl, Andras, Perrotta, Cristiana, Perrotta, Ida, Pestell, Richard G., Petersen, Morten, Petrache, Irina, Petrovski, Goran, Pfirrmann, Thorsten, Pfister, Astrid S., Philips, Jennifer A., Pi, Huifeng, Picca, Anna, Pickrell, Alicia M., Picot, Sandy, Pierantoni, Giovanna M., Pierdominici, Marina, Pierre, Philippe, Pierrefite-Carle, Valérie, Pierzynowska, Karolina, Pietrocola, Federico, Pietruczuk, Miroslawa, Pignata, Claudio, Pimentel-Muiños, Felipe X., Pinar, Mario, Pinheiro, Roberta O., Pinkas-Kramarski, Ronit, Pinton, Paolo, Pircs, Karolina, Piya, Sujan, Pizzo, Paola, Plantinga, Theo S., Platta, Harald W., Plaza-Zabala, Ainhoa, Plomann, Markus, Plotnikov, Egor Y., Plun-Favreau, Helene, Pluta, Ryszard, Pocock, Roger, Pöggeler, Stefanie, Pohl, Christian, Poirot, Marc, Poletti, Angelo, Ponpuak, Marisa, Popelka, Hana, Popova, Blagovesta, Porta, Helena, Porte Alcon, Soledad, Portilla-Fernandez, Eliana, Post, Martin, Potts, Malia B., Poulton, Joanna, Powers, Ted, Prahlad, Veena, Prajsnar, Tomasz K., Praticò, Domenico, Prencipe, Rosaria, Priault, Muriel, Proikas-Cezanne, Tassula, Promponas, Vasilis J., Proud, Christopher G., Puertollano, Rosa, Puglielli, Luigi, Pulinilkunnil, Thomas, Puri, Deepika, Puri, Rajat, Puyal, Julien, Qi, Xiaopeng, Qi, Yongmei, Qian, Wenbin, Qiang, Lei, Qiu, Yu, Quadrilatero, Joe, Quarleri, Jorge, Raben, Nina, Rabinowich, Hannah, Ragona, Debora, Ragusa, Michael J., Rahimi, Nader, Rahmati, Marveh, Raia, Valeria, Raimundo, Nuno, Rajasekaran, Namakkal-Soorappan, Ramachandra Rao, Sriganesh, Rami, Abdelhaq, Ramírez-Pardo, Ignacio, Ramsden, David B., Randow, Felix, Rangarajan, Pundi N., Ranieri, Danilo, Rao, Hai, Rao, Lang, Rao, Rekha, Rathore, Sumit, Ratnayaka, J. Arjuna, Ratovitski, Edward A., Ravanan, Palaniyandi, Ravegnini, Gloria, Ray, Swapan K., Razani, Babak, Rebecca, Vito, Reggiori, Fulvio, Régnier-Vigouroux, Anne, Reichert, Andreas S., Reigada, David, Reiling, Jan H., Rein, Theo, Reipert, Siegfried, Rekha, Rokeya Sultana, Ren, Hongmei, Ren, Jun, Ren, Weichao, Renault, Tristan, Renga, Giorgia, Reue, Karen, Rewitz, Kim, Ribeiro de Andrade Ramos, Bruna, Riazuddin, S. Amer, Ribeiro-Rodrigues, Teresa M., Ricci, Jean-Ehrland, Ricci, Romeo, Riccio, Victoria, Richardson, Des R., Rikihisa, Yasuko, Risbud, Makarand V., Risueño, Ruth M., Ritis, Konstantinos, Rizza, Salvatore, Rizzuto, Rosario, Roberts, Helen C., Roberts, Luke D., Robinson, Katherine J., Roccheri, Maria Carmela, Rocchi, Stephane, Rodney, George G., Rodrigues, Tiago, Rodrigues Silva, Vagner Ramon, Rodriguez, Amaia, Rodriguez-Barrueco, Ruth, Rodriguez-Henche, Nieves, Rodriguez-Rocha, Humberto, Roelofs, Jeroen, Rogers, Robert S., Rogov, Vladimir V., Rojo, Ana I., Rolka, Krzysztof, Romanello, Vanina, Romani, Luigina, Romano, Alessandra, Romano, Patricia S., Romeo-Guitart, David, Romero, Luis C., Romero, Montserrat, Roney, Joseph C., Rongo, Christopher, Roperto, Sante, Rosenfeldt, Mathias T., Rosenstiel, Philip, Rosenwald, Anne G., Roth, Kevin A., Roth, Lynn, Roth, Steven, Rouschop, Kasper M.A., Roussel, Benoit D., Roux, Sophie, Rovere-Querini, Patrizia, Roy, Ajit, Rozieres, Aurore, Ruano, Diego, Rubinsztein, David C., Rubtsova, Maria P., Ruckdeschel, Klaus, Ruckenstuhl, Christoph, Rudolf, Emil, Rudolf, Rüdiger, Ruggieri, Alessandra, Ruparelia, Avnika Ashok, Rusmini, Paola, Russell, Ryan R., Russo, Gian Luigi, Russo, Maria, Russo, Rossella, Ryabaya, Oxana O., Ryan, Kevin M., Ryu, Kwon-Yul, Sabater-Arcis, Maria, Sachdev, Ulka, Sacher, Michael, Sachse, Carsten, Sadhu, Abhishek, Sadoshima, Junichi, Safren, Nathaniel, Saftig, Paul, Sagona, Antonia P., Sahay, Gaurav, Sahebkar, Amirhossein, Sahin, Mustafa, Sahin, Ozgur, Sahni, Sumit, Saito, Nayuta, Saito, Shigeru, Saito, Tsunenori, Sakai, Ryohei, Sakai, Yasuyoshi, Sakamaki, Jun-Ichi, Saksela, Kalle, Salazar, Gloria, Salazar-Degracia, Anna, Salekdeh, Ghasem H., Saluja, Ashok K., Sampaio-Marques, Belém, Sanchez, Maria Cecilia, Sanchez-Alcazar, Jose A., Sanchez-Vera, Victoria, Sancho-Shimizu, Vanessa, Sanderson, J. Thomas, Sandri, Marco, Santaguida, Stefano, Santambrogio, Laura, Santana, Magda M., Santoni, Giorgio, Sanz, Alberto, Sanz, Pascual, Saran, Shweta, Sardiello, Marco, Sargeant, Timothy J., Sarin, Apurva, Sarkar, Chinmoy, Sarkar, Sovan, Sarrias, Maria-Rosa, Sarkar, Surajit, Sarmah, Dipanka Tanu, Sarparanta, Jaakko, Sathyanarayan, Aishwarya, Sathyanarayanan, Ranganayaki, Scaglione, K. Matthew, Scatozza, Francesca, Schaefer, Liliana, Schafer, Zachary T., Schaible, Ulrich E., Schapira, Anthony H.V., Scharl, Michael, Schatzl, Hermann M., Schein, Catherine H., Scheper, Wiep, Scheuring, David, Schiaffino, Maria Vittoria, Schiappacassi, Monica, Schindl, Rainer, Schlattner, Uwe, Schmidt, Oliver, Schmitt, Roland, Schmidt, Stephen D., Schmitz, Ingo, Schmukler, Eran, Schneider, Anja, Schneider, Bianca E., Schober, Romana, Schoijet, Alejandra C., Schott, Micah B., Schramm, Michael, Schröder, Bernd, Schuh, Kai, Schüller, Christoph, Schulze, Ryan J., Schürmanns, Lea, Schwamborn, Jens C., Schwarten, Melanie, Scialo, Filippo, Sciarretta, Sebastiano, Scott, Melanie J., Scotto, Kathleen W., Scovassi, A. Ivana, Scrima, Andrea, Scrivo, Aurora, Sebastian, David, Sebti, Salwa, Sedej, Simon, Segatori, Laura, Segev, Nava, Seglen, Per O., Seiliez, Iban, Seki, Ekihiro, Selleck, Scott B., Sellke, Frank W., Selsby, Joshua T., Sendtner, Michael, Senturk, Serif, Seranova, Elena, Sergi, Consolato, Serra-Moreno, Ruth, Sesaki, Hiromi, Settembre, Carmine, Setty, Subba Rao Gangi, Sgarbi, Gianluca, Sha, Ou, Shacka, John J., Shah, Javeed A., Shang, Dantong, Shao, Changshun, Shao, Feng, Sharbati, Soroush, Sharkey, Lisa M., Sharma, Dipali, Sharma, Gaurav, Sharma, Kulbhushan, Sharma, Pawan, Sharma, Surendra, Shen, Han-Ming, Shen, Hongtao, Shen, Jiangang, Shen, Ming, Shen, Weili, Shen, Zheni, Sheng, Rui, Sheng, Zhi, Sheng, Zu-Hang, Shi, Jianjian, Shi, Xiaobing, Shi, Ying-Hong, Shiba-Fukushima, Kahori, Shieh, Jeng-Jer, Shimada, Yohta, Shimizu, Shigeomi, Shimozawa, Makoto, Shintani, Takahiro, Shoemaker, Christopher J., Shojaei, Shahla, Shoji, Ikuo, Shravage, Bhupendra V., Shridhar, Viji, Shu, Chih-Wen, Shu, Hong-Bing, Shui, Ke, Shukla, Arvind K., Shutt, Timothy E., Sica, Valentina, Siddiqui, Aleem, Sierra, Amanda, Sierra-Torre, Virginia, Signorelli, Santiago, Sil, Payel, Silva, Bruno J. de Andrade, Silva, Johnatas D., Silva-Pavez, Eduardo, Silvente-Poirot, Sandrine, Simmonds, Rachel E., Simon, Anna Katharina, Simon, Hans-Uwe, Simons, Matias, Singh, Anurag, Singh, Lalit P., Singh, Rajat, Singh, Shivendra V., Singh, Shrawan K., Singh, Sudha B., Singh, Sunaina, Singh, Surinder Pal, Sinha, Debasish, Sinha, Rohit Anthony, Sinha, Sangita, Sirko, Agnieszka, Sirohi, Kapil, Sivridis, Efthimios L., Skendros, Panagiotis, Skirycz, Aleksandra, Slaninová, Iva, Smaili, Soraya S., Smertenko, Andrei, Smith, Matthew D., Soenen, Stefaan J., Sohn, Eun Jung, Sok, Sophia P. M., Solaini, Giancarlo, Soldati, Thierry, Soleimanpour, Scott A., Soler, Rosa M., Solovchenko, Alexei, Somarelli, Jason A., Sonawane, Avinash, Song, Fuyong, Song, Hyun Kyu, Song, Ju-Xian, Song, Kunhua, Song, Zhiyin, Soria, Leandro R., Sorice, Maurizio, Soukas, Alexander A., Soukup, Sandra-Fausia, Sousa, Diana, Sousa, Nadia, Spagnuolo, Paul A., Spector, Stephen A., Srinivas Bharath, M. M., St. Clair, Daret, Stagni, Venturina, Staiano, Leopoldo, Stalnecker, Clint A., Stankov, Metodi V., Stathopulos, Peter B., Stefan, Katja, Stefan, Sven Marcel, Stefanis, Leonidas, Steffan, Joan S., Steinkasserer, Alexander, Stenmark, Harald, Sterneckert, Jared, Stevens, Craig, Stoka, Veronika, Storch, Stephan, Stork, Björn, Strappazzon, Flavie, Strohecker, Anne Marie, Stupack, Dwayne G., Su, Huanxing, Su, Ling-Yan, Su, Longxiang, Suarez-Fontes, Ana M., Subauste, Carlos S., Subbian, Selvakumar, Subirada, Paula V., Sudhandiran, Ganapasam, Sue, Carolyn M., Sui, Xinbing, Summers, Corey, Sun, Guangchao, Sun, Jun, Sun, Kang, Sun, Meng-xiang, Sun, Qiming, Sun, Yi, Sun, Zhongjie, Sunahara, Karen K.S., Sundberg, Eva, Susztak, Katalin, Sutovsky, Peter, Suzuki, Hidekazu, Sweeney, Gary, Symons, J. David, Sze, Stephen Cho Wing, Szewczyk, Nathaniel J., Tabęcka-Łonczynska, Anna, Tabolacci, Claudio, Tacke, Frank, Taegtmeyer, Heinrich, Tafani, Marco, Tagaya, Mitsuo, Tai, Haoran, Tait, Stephen W. 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Richard, Waguri, Satoshi, Waite, Kenrick A, Wakatsuki, Shuji, Walker, David W, Walker, Mark J, Walker, Simon A, Walter, Jochen, Wandosell, Francisco G, Wang, Bo, Wang, Chao-Yung, Wang, Chen, Wang, Chenran, Wang, Chenwei, Wang, Cun-Yu, Wang, Dong, Wang, Fangyang, Wang, Feng, Wang, Fengming, Wang, Guansong, Wang, Han, Wang, Hao, Wang, Hexiang, Wang, Hong-Gang, Wang, Jianrong, Wang, Jigang, Wang, Jiou, Wang, Jundong, Wang, Kui, Wang, Lianrong, Wang, Liming, Wang, Maggie Haitian, Wang, Meiqing, Wang, Nanbu, Wang, Pengwei, Wang, Peipei, Wang, Ping, Wang, Qing Jun, Wang, Qing, Wang, Qing Kenneth, Wang, Qiong A, Wang, Wen-Tao, Wang, Wuyang, Wang, Xinnan, Wang, Xuejun, Wang, Yan, Wang, Yanchang, Wang, Yanzhuang, Wang, Yen-Yun, Wang, Yihua, Wang, Yipeng, Wang, Yu, Wang, Yuqi, Wang, Zhe, Wang, Zhenyu, Wang, Zhouguang, Warnes, Gary, Warnsmann, Verena, Watada, Hirotaka, Watanabe, Eizo, Watchon, Maxinne, Wawrzyńska, Anna, Weaver, Timothy E, Wegrzyn, Grzegorz, Wehman, Ann M, Wei, Huafeng, Wei, Lei, Wei, Taotao, Wei, Yongjie, Weiergräber, Oliver H, Weihl, Conrad C, Weindl, Günther, Weiskirchen, Ralf, Wells, Alan, Wen, Runxia H, Wen, Xin, Werner, Antonia, Weykopf, Beatrice, Wheatley, Sally P, Whitton, J Lindsay, Whitworth, Alexander J, Wiktorska, Katarzyna, Wildenberg, Manon E, Wileman, Tom, Wilkinson, Simon, Willbold, Dieter, Williams, Brett, Williams, Robin S B, Williams, Roger L, Williamson, Peter R, Wilson, Richard A, Winner, Beate, Winsor, Nathaniel J, Witkin, Steven S, Wodrich, Harald, Woehlbier, Ute, Wollert, Thoma, Wong, Esther, Wong, Jack Ho, Wong, Richard W, Wong, Vincent Kam Wai, Wong, W Wei-Lynn, Wu, An-Guo, Wu, Chengbiao, Wu, Jian, Wu, Junfang, Wu, Kenneth K, Wu, Min, Wu, Shan-Ying, Wu, Shengzhou, Wu, Shu-Yan, Wu, Shufang, Wu, William K K, Wu, Xiaohong, Wu, Xiaoqing, Wu, Yao-Wen, Wu, Yihua, Xavier, Ramnik J, Xia, Hongguang, Xia, Lixin, Xia, Zhengyuan, Xiang, Ge, Xiang, Jin, Xiang, Mingliang, Xiang, Wei, Xiao, Bin, Xiao, Guozhi, Xiao, Hengyi, Xiao, Hong-Tao, Xiao, Jian, Xiao, Lan, Xiao, Shi, Xiao, Yin, Xie, Baoming, Xie, Chuan-Ming, Xie, Min, Xie, Yuxiang, Xie, Zhiping, Xie, Zhonglin, Xilouri, Maria, Xu, Congfeng, Xu, En, Xu, Haoxing, Xu, Jing, Xu, JinRong, Xu, Liang, Xu, Wen Wen, Xu, Xiulong, Xue, Yu, Yakhine-Diop, Sokhna M S, Yamaguchi, Masamitsu, Yamaguchi, Osamu, Yamamoto, Ai, Yamashina, Shunhei, Yan, Shengmin, Yan, Shian-Jang, Yan, Zhen, Yanagi, Yasuo, Yang, Chuanbin, Yang, Dun-Sheng, Yang, Huan, Yang, Huang-Tian, Yang, Hui, Yang, Jin-Ming, Yang, Jing, Yang, Jingyu, Yang, Ling, Yang, Liu, Yang, Ming, Yang, Pei-Ming, Yang, Qian, Yang, Seungwon, Yang, Shu, Yang, Shun-Fa, Yang, Wannian, Yang, Wei Yuan, Yang, Xiaoyong, Yang, Xuesong, Yang, Yi, Yang, Ying, Yao, Honghong, Yao, Shenggen, Yao, Xiaoqiang, Yao, Yong-Gang, Yao, Yong-Ming, Yasui, Takahiro, Yazdankhah, Meysam, Yen, Paul M, Yi, Cong, Yin, Xiao-Ming, Yin, Yanhai, Yin, Zhangyuan, Yin, Ziyi, Ying, Meidan, Ying, Zheng, Yip, Calvin K, Yiu, Stephanie Pei Tung, Yoo, Young H, Yoshida, Kiyotsugu, Yoshii, Saori R, Yoshimori, Tamotsu, Yousefi, Bahman, Yu, Boxuan, Yu, Haiyang, Yu, Jun, Yu, Li, Yu, Ming-Lung, Yu, Seong-Woon, Yu, Victor C, Yu, W Haung, Yu, Zhengping, Yu, Zhou, Yuan, Junying, Yuan, Ling-Qing, Yuan, Shilin, Yuan, Shyng-Shiou F, Yuan, Yanggang, Yuan, Zengqiang, Yue, Jianbo, Yue, Zhenyu, Yun, Jeanho, Yung, Raymond L, Zacks, David N, Zaffagnini, Gabriele, Zambelli, Vanessa O, Zanella, Isabella, Zang, Qun S, Zanivan, Sara, Zappavigna, Silvia, Zaragoza, Pilar, Zarbalis, Konstantinos S, Zarebkohan, Amir, Zarrouk, Amira, Zeitlin, Scott O, Zeng, Jialiu, Zeng, Ju-Deng, Žerovnik, Eva, Zhan, Lixuan, Zhang, Bin, Zhang, Donna D, Zhang, Hanlin, Zhang, Hong, Zhang, Honghe, Zhang, Huafeng, Zhang, Huaye, Zhang, Hui, Zhang, Hui-Ling, Zhang, Jianbin, Zhang, Jianhua, Zhang, Jing-Pu, Zhang, Kalin Y B, Zhang, Leshuai W, Zhang, Lin, Zhang, Lisheng, Zhang, Lu, Zhang, Luoying, Zhang, Menghuan, Zhang, Peng, Zhang, Sheng, Zhang, Wei, Zhang, Xiangnan, Zhang, Xiao-Wei, Zhang, Xiaolei, Zhang, Xiaoyan, Zhang, Xin, Zhang, Xinxin, Zhang, Xu Dong, Zhang, Yang, Zhang, Yanjin, Zhang, Yi, Zhang, Ying-Dong, Zhang, Yingmei, Zhang, Yuan-Yuan, Zhang, Yuchen, Zhang, Zhe, Zhang, Zhengguang, Zhang, Zhibing, Zhang, Zhihai, Zhang, Zhiyong, Zhang, Zili, Zhao, Haobin, Zhao, Lei, Zhao, Shuang, Zhao, Tongbiao, Zhao, Xiao-Fan, Zhao, Ying, Zhao, Yongchao, Zhao, Yongliang, Zhao, Yuting, Zheng, Guoping, Zheng, Kai, Zheng, Ling, Zheng, Shizhong, Zheng, Xi-Long, Zheng, Yi, Zheng, Zu-Guo, Zhivotovsky, Bori, Zhong, Qing, Zhou, Ao, Zhou, Ben, Zhou, Cefan, Zhou, Gang, Zhou, Hao, Zhou, Hong, Zhou, Hongbo, Zhou, Jie, Zhou, Jing, Zhou, Jiyong, Zhou, Kailiang, Zhou, Rongjia, Zhou, Xu-Jie, Zhou, Yanshuang, Zhou, Yinghong, Zhou, Yubin, Zhou, Zheng-Yu, Zhou, Zhou, Zhu, Binglin, Zhu, Changlian, Zhu, Guo-Qing, Zhu, Haining, Zhu, Hongxin, Zhu, Hua, Zhu, Wei-Guo, Zhu, Yanping, Zhu, Yushan, Zhuang, Haixia, Zhuang, Xiaohong, Zientara-Rytter, Katarzyna, Zimmermann, Christine M, Ziviani, Elena, Zoladek, Teresa, Zong, Wei-Xing, Zorov, Dmitry B, Zorzano, Antonio, Zou, Weiping, Zou, Zhen, Zou, Zhengzhi, Zuryn, Steven, Zwerschke, Werner, Brand-Saberi, Beate, Dong, X Charlie, Kenchappa, Chandra Shekar, Li, Zuguo, Lin, Yong, Oshima, Shigeru, Rong, Yueguang, Sluimer, Judith C, Stallings, Christina L, Tong, Chun-Kit, University of Michigan [Ann Arbor], University of Michigan System, Institut Pasteur d'Iran, Réseau International des Instituts Pasteur (RIIP), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre de Recherches sur la Cognition Animale - UMR5169 (CRCA), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre méditerranéen de médecine moléculaire (C3M), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut de Biologie Valrose (IBV), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Maladies et hormones du système nerveux (DHNS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University of South Carolina Upstate (USC Upstate), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), The Francis Crick Institute [London], Royal Free Hospital [London, UK], Physiologie et physiopathologie endocriniennes (PHYSENDO), Nutrition, Métabolisme, Aquaculture (NuMéA), Université de Pau et des Pays de l'Adour (UPPA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes (LBMCE), Institut de biologie physico-chimique (IBPC (FR_550)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Department of Molecular Medicine, Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire de biogenèse membranaire (LBM), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université du Québec à Trois-Rivières (UQTR), Laboratory of Pathogen Host Interactions [Montpellier] (LPHI), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Université Paris 13 (UP13)-Université Paris-Sud - Paris 11 (UP11)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), OEil, nutrition et signalisation cellulaire [CSGA], Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biologie des Bactéries intracellulaires - Biology of Intracellular Bacteria, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris], Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), UMR E4320 (TIRO-MATOs), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'ingénierie des systèmes macromoléculaires (LISM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Métabolisme, Cancer et Immunité (CRC - UMR_S 1138), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Plateforme de métabolomique, Direction de la recherche [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Karolinska Institutet [Stockholm], Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] (BIO-PEROXIL), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut Jean-Pierre Bourgin (IJPB), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Clermont-Ferrand, Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologia Celular [Rio de Janeiro], Instituto Oswaldo Cruz / Oswaldo Cruz Institute [Rio de Janeiro] (IOC), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Laboratoire d'Optique et Biosciences (LOB), École polytechnique (X)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), SFR Biosciences, Laboratoire de Génétique et Pathologie des Mollusques Marins (LGPMM), Santé, Génétique et Microbiologie des Mollusques (SGMM), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut d’Etudes Avancées de l’Université de Strasbourg - Institute for Advanced Study (USIAS), Université de Strasbourg (UNISTRA), Sanofi [Vitry-sur-Seine], SANOFI Recherche, Micro-environnement tumoral et résistance aux traitements, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'Immunologie de Marseille - Luminy (CIML), Universidade de Aveiro, Shanghai Jiao Tong University [Shanghai], Biochimie membranaire et transport / Membrane Biochemistry and Transport, Institut Pasteur [Paris] (IP), Institut de pharmacologie et de biologie structurale (IPBS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), National Institute of General Medical Sciences [GM131919], Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), University of South Carolina Upstate (USC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Physiologie et physiopathologie endocriniennes, Centre National de la Recherche Scientifique (CNRS)-Institut de biologie physico-chimique (IBPC (FR_550)), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]-Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), LPHI - Laboratory of Pathogen Host Interactions (LPHI), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz (FIOCRUZ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Laboratoire de Génétique et Pathologie des Mollusques Marins, 17390 La Tremblade, France. (LGPMM), Santé, Génétique et Microbiologie des Mollusques (IFREMER SG2M), Institut Français de Recherche pour l'Exploitation de la Mer - Atlantique (IFREMER Atlantique), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut Français de Recherche pour l'Exploitation de la Mer - Atlantique (IFREMER Atlantique), Institut d’Etudes Avancées de l’Université de Strasbourg (USIAS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut Pasteur [Paris], Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Life Sciences Institute and Department of Molecular, Cellular, and Developmental Biology and Biological Chemistry, University of Michigan System-University of Michigan System, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences. Johannes Gutenberg University, Division of Cardiology, Medical University of Graz, Department of Hepatitis and HIV, Pasteur Institute of Iran, Department of Molecular Signal Processing, Leibniz Institute for Plant Biochemistry, Department of Biochemistry and Food Science, The Hebrew University of Jerusalem (HUJ), RNA and Autophagy Group, Danish Cancer Society Research Center, Biotech Research and Innovation Centre (BRIC), University of Copenhagen = Københavns Universitet (KU), Department of Medical Biology, The Arctic University of Norway (UiT), CIBERNED and Universidad de La Laguna, ITB, Hospital Universitario De Canarias, UC Davis Division of Rheumatology, Allergy and Clinical Immunology, School of Medicine, University of California, Department of Biochemistry [University of Toronto], University of Toronto, Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria., Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Protein Structure and Function Section, National Institutes of Health, National Eye institute, Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Faculty of Health Sciences, Division of Nephrology and Birmingham VA Medical Center, University of Alabama at Birmingham [ Birmingham] (UAB), Inflammation Research Center, Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università degli studi di Palermo - University of Palermo, Cell Death Research & Therapy (CDRT) Lab, Department of Cellular & Molecular Medicine, Center for Cancer Biology, Indian Institute of Technology, The MRC Protein Phosphorylation and Ubiquitylation Unit [Dundee, UK] (School of Life Sciences), University of Dundee, Department of Pathology [Dallas], University of Texas Southwestern Medical Center [Dallas], Department of Biology, Colby College, Departments of Otorhinolaryngology Head & Neck Surgery, Ophthalmology and Visual Science, University of Maryland School of Medicine, University of Maryland System-University of Maryland System, Center for Integrative Biology, and Geroscience Center for Brain Health and Metabolism, Universidad Mayor [Santiago de Chile], Department of Experimental Medical Science, Cell Death, Lysosomes and Artificial Intelligence Group, Lund University [Lund], College of Bioresource Sciences, Nihon University, Department of Molecular Biology and Genetics and KUTTAM Research Center for Translational Medicine, Koc University, School of Medicine, Istanbul, School of Medicine. Laboratory of Clinical Microbiology and Microbial Pathogenesis, University of Crete [Heraklion] (UOC), Institute of Molecular Biology and Biotechnology (IMBB-FORTH), Foundation for Research and Technology - Hellas (FORTH), Cancer Therapeutics Unit, The Institute of Cancer Research, London, UK., Pharmaceutical Sciences Department, College of Pharmacy, Gulf Medical University [Ajman, UAE], Department of Pathology and Bosch Institute, University of Sydney, The University of Sydney, Department of Research, Insight Institute of Neurosurgery & Neuroscience, Departments of Medicine and Oncology and Segal Cancer Centre, McGill University = Université McGill [Montréal, Canada], Center for Molecular and Cellular Bioengineering [TU Dresden, Germany] (CMCB), Technische Universität Dresden = Dresden University of Technology (TU Dresden), Departamento de Psicología Experimental, Universidad de Sevilla, Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Johns Hopkins University School of Medicine [Baltimore], Department of Pharmacy, Faculty of Science, University of Rajshahi, Rajshahi, Bangladesh, Islamic University of Gaza (IUG - IU Gaza), University of Manitoba [Winnipeg], University of Barcelona, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Cleveland Clinic, University of the Basque Country [Bizkaia] (UPV/EHU), Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, 'Dr. Héctor N. Torres' [Buenos Aires] (INGEBI), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Facultad de Ciencias Exactas y Naturales [Buenos Aires] (FCEyN), Universidad de Buenos Aires [Buenos Aires] (UBA)-Universidad de Buenos Aires [Buenos Aires] (UBA), Universidad de Buenos Aires [Buenos Aires] (UBA), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), The Wistar Institute, University of Buenos Aires [Argentina], Universidade do Porto, Excellence Laboratory LabEx DISTALZ, University of Pavia, University of Camerino, Telethon Institute of Genetics and Medicine = Istituto Telethon di Genetica e Medicina (TIGEM), Ohio State University [Columbus] (OSU), University of California [San Francisco] (UCSF), Aarhus University [Aarhus], Federal University of Sao Paulo (Unifesp), Nove de Julho University [Bauru] (UNINOVE ), Cedars-Sinai Medical Center, University of Bologna, City of Hope Comprehensive Cancer Center [Duarte], The University of Tennessee [Knoxville], Northeastern Ohio Medical University (NEOMED), Chronic Diseases Research Center (CEDOC), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University of Lisboa (NOVA)-Universidade Nova de Lisboa = NOVA University of Lisboa (NOVA), Max planck Institute for Biology of Ageing [Cologne], School of Biochemistry, University of Bristol, University of Helsinki, Inserm U1231 University UBFC Dijon, University of Valencia, National Center of Neurology and Psychiatry [Tokyo, Japan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), UMR 1195 Inserm, Université Paris Sud (Paris 11), Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This work was supported by the National Institute of General Medical Sciences [GM131919]. Due to space and other limitations, it is not possible to include all other sources of financial support., Debosch, Brian J, Degregori, Jame, Depamphilis, Melvin L, Hyung-Ryong Kim, Null, Kwak, Seongae, Larusso, Nicholas F, Liang, Yongtian, Lleonart, Matilde E, Macdougald, Ormond A, Macintosh, Gustavo C, Mackeigan, Jeffrey P, Mccarty, Nami, Mcdonald, Christine, Mcgill, Mitchell R, Mckenna, Sharon L, Mclaughlin, Bethann, Mcloughlin, Fionn, Mcniven, Mark A, Mcwilliams, Thomas G, Xu, Jinrong, Klionsky D.J., Abdel-Aziz A.K., Abdelfatah S., Abdellatif M., Abdoli A., Abel S., Abeliovich H., Abildgaard M.H., Abudu Y.P., Acevedo-Arozena A., Adamopoulos I.E., Adeli K., Adolph T.E., Adornetto A., Aflaki E., Agam G., Agarwal A., Aggarwal B.B., Agnello M., Agostinis P., Agrewala J.N., Agrotis A., Aguilar P.V., Ahmad S.T., Ahmed Z.M., Ahumada-Castro U., Aits S., Aizawa S., Akkoc Y., Akoumianaki T., Akpinar H.A., Al-Abd A.M., Al-Akra L., Al-Gharaibeh A., Alaoui-Jamali M.A., Alberti S., Alcocer-Gomez E., Alessandri C., Ali M., Alim Al-Bari M.A., Aliwaini S., Alizadeh J., Almacellas E., Almasan A., Alonso A., Alonso G.D., Altan-Bonnet N., Altieri D.C., Alvarez E.M.C., Alves S., Alves da Costa C., Alzaharna M.M., Amadio M., Amantini C., Amaral C., Ambrosio S., Amer A.O., Ammanathan V., An Z., Andersen S.U., Andrabi S.A., Andrade-Silva M., Andres A.M., Angelini S., Ann D., Anozie U.C., Ansari M.Y., Antas P., Antebi A., Anton Z., Anwar T., Apetoh L., Apostolova N., Araki T., Araki Y., Arasaki K., Araujo W.L., Araya J., Arden C., Arevalo M.-A., Arguelles S., Arias E., Arikkath J., Arimoto H., Ariosa A.R., Armstrong-James D., Arnaune-Pelloquin L., Aroca A., Arroyo D.S., Arsov I., Artero R., Asaro D.M.L., Aschner M., Ashrafizadeh M., Ashur-Fabian O., Atanasov A.G., Au A.K., Auberger P., Auner H.W., Aurelian L., Autelli R., Avagliano L., Avalos Y., Aveic S., Aveleira C.A., Avin-Wittenberg T., Aydin Y., Ayton S., Ayyadevara S., Azzopardi M., Baba M., Backer J.M., Backues S.K., Bae D.-H., Bae O.-N., Bae S.H., Baehrecke E.H., Baek A., Baek S.-H., Baek S.H., Bagetta G., Bagniewska-Zadworna A., Bai H., Bai J., Bai X., Bai Y., Bairagi N., Baksi S., Balbi T., Baldari C.T., Balduini W., Ballabio A., Ballester M., Balazadeh S., Balzan R., Bandopadhyay R., Banerjee S., Banreti A., Bao Y., Baptista M.S., Baracca A., Barbati C., Bargiela A., Barila D., Barlow P.G., Barmada S.J., Barreiro E., Barreto G.E., Bartek J., Bartel B., Bartolome A., Barve G.R., Basagoudanavar S.H., Bassham D.C., Bast R.C., Basu A., Batoko H., Batten I., Baulieu E.E., Baumgarner B.L., Bayry J., Beale R., Beau I., Beaumatin F., Bechara L.R.G., Beck G.R., Beers M.F., Begun J., Behrends C., Behrens G.M.N., Bei R., Bejarano E., Bel S., Behl C., Belaid A., Belgareh-Touze N., Bellarosa C., Belleudi F., Bello Perez M., Bello-Morales R., Beltran J.S.D.O., Beltran S., Benbrook D.M., Bendorius M., Benitez B.A., Benito-Cuesta I., Bensalem J., Berchtold M.W., Berezowska S., Bergamaschi D., Bergami M., Bergmann A., Berliocchi L., Berlioz-Torrent C., Bernard A., Berthoux L., Besirli C.G., Besteiro S., Betin V.M., Beyaert R., Bezbradica J.S., Bhaskar K., Bhatia-Kissova I., Bhattacharya R., Bhattacharya S., Bhattacharyya S., Bhuiyan M.S., Bhutia S.K., Bi L., Bi X., Biden T.J., Bijian K., Billes V.A., Binart N., Bincoletto C., Birgisdottir A.B., Bjorkoy G., Blanco G., Blas-Garcia A., Blasiak J., Blomgran R., Blomgren K., Blum J.S., Boada-Romero E., Boban M., Boesze-Battaglia K., Boeuf P., Boland B., Bomont P., Bonaldo P., Bonam S.R., Bonfili L., Bonifacino J.S., Boone B.A., Bootman M.D., Bordi M., Borner C., Bornhauser B.C., Borthakur G., Bosch J., Bose S., Botana L.M., Botas J., Boulanger C.M., Boulton M.E., Bourdenx M., Bourgeois B., Bourke N.M., Bousquet G., Boya P., Bozhkov P.V., Bozi L.H.M., Bozkurt T.O., Brackney D.E., Brandts C.H., Braun R.J., Braus G.H., Bravo-Sagua R., Bravo-San Pedro J.M., Brest P., Bringer M.-A., Briones-Herrera A., Broaddus V.C., Brodersen P., Brodsky J.L., Brody S.L., Bronson P.G., Bronstein J.M., Brown C.N., Brown R.E., Brum P.C., Brumell J.H., Brunetti-Pierri N., Bruno D., Bryson-Richardson R.J., Bucci C., Buchrieser C., Bueno M., Buitrago-Molina L.E., Buraschi S., Buch S., Buchan J.R., Buckingham E.M., Budak H., Budini M., Bultynck G., Burada F., Burgoyne J.R., Buron M.I., Bustos V., Buttner S., Butturini E., Byrd A., Cabas I., Cabrera-Benitez S., Cadwell K., Cai J., Cai L., Cai Q., Cairo M., Calbet J.A., Caldwell G.A., Caldwell K.A., Call J.A., Calvani R., Calvo A.C., Calvo-Rubio Barrera M., Camara N.O.S., Camonis J.H., Camougrand N., Campanella M., Campbell E.M., Campbell-Valois F.-X., Campello S., Campesi I., Campos J.C., Camuzard O., Cancino J., Candido de Almeida D., Canesi L., Caniggia I., Canonico B., Canti C., Cao B., Caraglia M., Carames B., Carchman E.H., Cardenal-Munoz E., Cardenas C., Cardenas L., Cardoso S.M., Carew J.S., Carle G.F., Carleton G., Carloni S., Carmona-Gutierrez D., Carneiro L.A., Carnevali O., Carosi J.M., Carra S., Carrier A., Carrier L., Carroll B., Carter A.B., Carvalho A.N., Casanova M., Casas C., Casas J., Cassioli C., Castillo E.F., Castillo K., Castillo-Lluva S., Castoldi F., Castori M., Castro A.F., Castro-Caldas M., Castro-Hernandez J., Castro-Obregon S., Catz S.D., Cavadas C., Cavaliere F., Cavallini G., Cavinato M., Cayuela M.L., Cebollada Rica P., Cecarini V., Cecconi F., Cechowska-Pasko M., Cenci S., Ceperuelo-Mallafre V., Cerqueira J.J., Cerutti J.M., Cervia D., Cetintas V.B., Cetrullo S., Chae H.-J., Chagin A.S., Chai C.-Y., Chakrabarti G., Chakrabarti O., Chakraborty T., Chami M., Chamilos G., Chan D.W., Chan E.Y.W., Chan E.D., Chan H.Y.E., Chan H.H., Chan H., Chan M.T.V., Chan Y.S., Chandra P.K., Chang C.-P., Chang C., Chang H.-C., Chang K., Chao J., Chapman T., Charlet-Berguerand N., Chatterjee S., Chaube S.K., Chaudhary A., Chauhan S., Chaum E., Checler F., Cheetham M.E., Chen C.-S., Chen G.-C., Chen J.-F., Chen L.L., Chen L., Chen M., Chen M.-K., Chen N., Chen Q., Chen R.-H., 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T., Renga G., Reue K., Rewitz K., Ribeiro de Andrade Ramos B., Riazuddin S.A., Ribeiro-Rodrigues T.M., Ricci J.-E., Ricci R., Riccio V., Richardson D.R., Rikihisa Y., Risbud M.V., Risueno R.M., Ritis K., Rizza S., Rizzuto R., Roberts H.C., Roberts L.D., Robinson K.J., Roccheri M.C., Rocchi S., Rodney G.G., Rodrigues T., Rodrigues Silva V.R., Rodriguez A., Rodriguez-Barrueco R., Rodriguez-Henche N., Rodriguez-Rocha H., Roelofs J., Rogers R.S., Rogov V.V., Rojo A.I., Rolka K., Romanello V., Romani L., Romano A., Romano P.S., Romeo-Guitart D., Romero L.C., Romero M., Roney J.C., Rongo C., Roperto S., Rosenfeldt M.T., Rosenstiel P., Rosenwald A.G., Roth K.A., Roth L., Roth S., Rouschop K.M.A., Roussel B.D., Roux S., Rovere-Querini P., Roy A., Rozieres A., Ruano D., Rubinsztein D.C., Rubtsova M.P., Ruckdeschel K., Ruckenstuhl C., Rudolf E., Rudolf R., Ruggieri A., Ruparelia A.A., Rusmini P., Russell R.R., Russo G.L., Russo M., Russo R., Ryabaya O.O., Ryan K.M., Ryu K.-Y., Sabater-Arcis M., Sachdev U., Sacher M., Sachse C., Sadhu A., Sadoshima J., Safren N., Saftig P., Sagona A.P., Sahay G., Sahebkar A., Sahin M., Sahin O., Sahni S., Saito N., Saito S., Saito T., Sakai R., Sakai Y., Sakamaki J.-I., Saksela K., Salazar G., Salazar-Degracia A., Salekdeh G.H., Saluja A.K., Sampaio-Marques B., Sanchez M.C., Sanchez-Alcazar J.A., Sanchez-Vera V., Sancho-Shimizu V., Sanderson J.T., Sandri M., Santaguida S., Santambrogio L., Santana M.M., Santoni G., Sanz A., Sanz P., Saran S., Sardiello M., Sargeant T.J., Sarin A., Sarkar C., Sarkar S., Sarrias M.-R., Sarmah D.T., Sarparanta J., Sathyanarayan A., Sathyanarayanan R., Scaglione K.M., Scatozza F., Schaefer L., Schafer Z.T., Schaible U.E., Schapira A.H.V., Scharl M., Schatzl H.M., Schein C.H., Scheper W., Scheuring D., Schiaffino M.V., Schiappacassi M., Schindl R., Schlattner U., Schmidt O., Schmitt R., Schmidt S.D., Schmitz I., Schmukler E., Schneider A., Schneider B.E., Schober R., Schoijet A.C., Schott M.B., Schramm M., Schroder 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E., Silvente-Poirot S., Simmonds R.E., Simon A.K., Simon H.-U., Simons M., Singh A., Singh L.P., Singh R., Singh S.V., Singh S.K., Singh S.B., Singh S., Singh S.P., Sinha D., Sinha R.A., Sinha S., Sirko A., Sirohi K., Sivridis E.L., Skendros P., Skirycz A., Slaninova I., Smaili S.S., Smertenko A., Smith M.D., Soenen S.J., Sohn E.J., Sok S.P.M., Solaini G., Soldati T., Soleimanpour S.A., Soler R.M., Solovchenko A., Somarelli J.A., Sonawane A., Song F., Song H.K., Song J.-X., Song K., Song Z., Soria L.R., Sorice M., Soukas A.A., Soukup S.-F., Sousa D., Sousa N., Spagnuolo P.A., Spector S.A., Srinivas Bharath M.M., St. Clair D., Stagni V., Staiano L., Stalnecker C.A., Stankov M.V., Stathopulos P.B., Stefan K., Stefan S.M., Stefanis L., Steffan J.S., Steinkasserer A., Stenmark H., Sterneckert J., Stevens C., Stoka V., Storch S., Stork B., Strappazzon F., Strohecker A.M., Stupack D.G., Su H., Su L.-Y., Su L., Suarez-Fontes A.M., Subauste C.S., Subbian S., Subirada P.V., Sudhandiran G., Sue C.M., Sui X., Summers C., Sun G., Sun J., Sun K., Sun M.-X., Sun Q., Sun Y., Sun Z., Sunahara K.K.S., Sundberg E., Susztak K., Sutovsky P., Suzuki H., Sweeney G., Symons J.D., Sze S.C.W., Szewczyk N.J., Tabecka-Lonczynska A., Tabolacci C., Tacke F., Taegtmeyer H., Tafani M., Tagaya M., Tai H., Tait S.W.G., Takahashi Y., Takats S., Talwar P., Tam C., Tam S.Y., Tampellini D., Tamura A., Tan C.T., Tan E.-K., Tan Y.-Q., Tanaka M., Tang D., Tang J., Tang T.-S., Tanida I., Tao Z., Taouis M., Tatenhorst L., Tavernarakis N., Taylor A., Taylor G.A., Taylor J.M., Tchetina E., Tee A.R., Tegeder I., Teis D., Teixeira N., Teixeira-Clerc F., Tekirdag K.A., Tencomnao T., Tenreiro S., Tepikin A.V., Testillano P.S., Tettamanti G., Tharaux P.-L., Thedieck K., Thekkinghat A.A., Thellung S., Thinwa J.W., Thirumalaikumar V.P., Thomas S.M., Thomes P.G., Thorburn A., Thukral L., Thum T., Thumm M., Tian L., Tichy A., Till A., Timmerman V., Titorenko V.I., Todi S.V., Todorova K., Toivonen J.M., Tomaipitinca L., Tomar D., Tomas-Zapico C., Tomic S., Tong B.C.-K., Tong C., Tong X., Tooze S.A., Torgersen M.L., Torii S., Torres-Lopez L., Torriglia A., Towers C.G., Towns R., Toyokuni S., Trajkovic V., Tramontano D., Tran Q.-G., Travassos L.H., Trelford C.B., Tremel S., Trougakos I.P., Tsao B.P., Tschan M.P., Tse H.-F., Tse T.F., Tsugawa H., Tsvetkov A.S., Tumbarello D.A., Tumtas Y., Tunon M.J., Turcotte S., Turk B., Turk V., Turner B.J., Tuxworth R.I., Tyler J.K., Tyutereva E.V., Uchiyama Y., Ugun-Klusek A., Uhlig H.H., Ulamek-Koziol M., Ulasov I.V., Umekawa M., Ungermann C., Unno R., Urbe S., Uribe-Carretero E., Ustun S., Uversky V.N., Vaccari T., Vaccaro M.I., Vahsen B.F., Vakifahmetoglu-Norberg H., Valdor R., Valente M.J., Valko A., Vallee R.B., Valverde A.M., Van den Berghe G., van der Veen S., Van Kaer L., van Loosdregt J., van Wijk S.J.L., Vandenberghe W., Vanhorebeek I., Vannier-Santos M.A., Vannini N., Vanrell M.C., Vantaggiato C., Varano G., Varela-Nieto I., Varga M., Vasconcelos M.H., Vats S., Vavvas D.G., Vega-Naredo I., Vega-Rubin-de-Celis S., Velasco G., Velazquez A.P., Vellai T., Vellenga E., Velotti F., Verdier M., Verginis P., Vergne I., Verkade P., Verma M., Verstreken P., Vervliet T., Vervoorts J., Vessoni A.T., Victor V.M., Vidal M., Vidoni C., Vieira O.V., Vierstra R.D., Vigano S., Vihinen H., Vijayan V., Vila M., Vilar M., Villalba J.M., Villalobo A., Villarejo-Zori B., Villarroya F., Villarroya J., Vincent O., Vindis C., Viret C., Viscomi M.T., Visnjic D., Vitale I., Vocadlo D.J., Voitsekhovskaja O.V., Volonte C., Volta M., Vomero M., Von Haefen C., Vooijs M.A., Voos W., Vucicevic L., Wade-Martins R., Waguri S., Waite K.A., Wakatsuki S., Walker D.W., Walker M.J., Walker S.A., Walter J., Wandosell F.G., Wang B., Wang C.-Y., Wang C., Wang D., Wang F., Wang G., Wang H., Wang H.-G., Wang J., Wang K., Wang L., Wang M.H., Wang M., Wang N., Wang P., Wang Q.J., Wang Q., Wang Q.K., Wang Q.A., Wang W.-T., Wang W., Wang X., Wang Y., Wang Y.-Y., Wang Z., Warnes G., Warnsmann V., Watada H., Watanabe E., Watchon M., Wawrzynska A., Weaver T.E., Wegrzyn G., Wehman A.M., Wei H., Wei L., Wei T., Wei Y., Weiergraber O.H., Weihl C.C., Weindl G., Weiskirchen R., Wells A., Wen R.H., Wen X., Werner A., Weykopf B., Wheatley S.P., Whitton J.L., Whitworth A.J., Wiktorska K., Wildenberg M.E., Wileman T., Wilkinson S., Willbold D., Williams B., Williams R.S.B., Williams R.L., Williamson P.R., Wilson R.A., Winner B., Winsor N.J., Witkin S.S., Wodrich H., Woehlbier U., Wollert T., Wong E., Wong J.H., Wong R.W., Wong V.K.W., Wong W.W.-L., Wu A.-G., Wu C., Wu J., Wu K.K., Wu M., Wu S.-Y., Wu S., Wu W.K.K., Wu X., Wu Y.-W., Wu Y., Xavier R.J., Xia H., Xia L., Xia Z., Xiang G., Xiang J., Xiang M., Xiang W., Xiao B., Xiao G., Xiao H., Xiao H.-T., Xiao J., Xiao L., Xiao S., Xiao Y., Xie B., Xie C.-M., Xie M., Xie Y., Xie Z., Xilouri M., Xu C., Xu E., Xu H., Xu J., Xu L., Xu W.W., Xu X., Xue Y., Yakhine-Diop S.M.S., Yamaguchi M., Yamaguchi O., Yamamoto A., Yamashina S., Yan S., Yan S.-J., Yan Z., Yanagi Y., Yang C., Yang D.-S., Yang H., Yang H.-T., Yang J.-M., Yang J., Yang L., Yang M., Yang P.-M., Yang Q., Yang S., Yang S.-F., Yang W., Yang W.Y., Yang X., Yang Y., Yao H., Yao S., Yao X., Yao Y.-G., Yao Y.-M., Yasui T., Yazdankhah M., Yen P.M., Yi C., Yin X.-M., Yin Y., Yin Z., Ying M., Ying Z., Yip C.K., Yiu S.P.T., Yoo Y.H., Yoshida K., Yoshii S.R., Yoshimori T., Yousefi B., Yu B., Yu H., Yu J., Yu L., Yu M.-L., Yu S.-W., Yu V.C., Yu W.H., Yu Z., Yuan J., Yuan L.-Q., Yuan S., Yuan S.-S.F., Yuan Y., Yuan Z., Yue J., Yue Z., Yun J., Yung R.L., Zacks D.N., Zaffagnini G., Zambelli V.O., Zanella I., Zang Q.S., Zanivan S., Zappavigna S., Zaragoza P., Zarbalis K.S., Zarebkohan A., Zarrouk A., Zeitlin S.O., Zeng J., Zeng J.-D., Zerovnik E., Zhan L., Zhang B., Zhang D.D., Zhang H., Zhang H.-L., Zhang J., Zhang J.-P., Zhang K.Y.B., Zhang L.W., Zhang L., Zhang M., Zhang P., Zhang S., Zhang W., Zhang X., Zhang X.-W., Zhang X.D., Zhang Y., Zhang Y.-D., Zhang Y.-Y., Zhang Z., Zhao H., Zhao L., Zhao S., Zhao T., Zhao X.-F., Zhao Y., Zheng G., Zheng K., Zheng L., Zheng S., Zheng X.-L., Zheng Y., Zheng Z.-G., Zhivotovsky B., Zhong Q., Zhou A., Zhou B., Zhou C., Zhou G., Zhou H., Zhou J., Zhou K., Zhou R., Zhou X.-J., Zhou Y., Zhou Z.-Y., Zhou Z., Zhu B., Zhu C., Zhu G.-Q., Zhu H., Zhu W.-G., Zhu Y., Zhuang H., Zhuang X., Zientara-Rytter K., Zimmermann C.M., Ziviani E., Zoladek T., Zong W.-X., Zorov D.B., Zorzano A., Zou W., Zou Z., Zuryn S., Zwerschke W., Brand-Saberi B., Dong X.C., Kenchappa C.S., Lin Y., Oshima S., Rong Y., Sluimer J.C., Stallings C.L., Tong C.-K., COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Klionsky, D. 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H, Shui, K, Shukla, A, Shutt, T, Sica, V, Siddiqui, A, Sierra, A, Sierra-Torre, V, Signorelli, S, Sil, P, Silva, B, Silva, J, Silva-Pavez, E, Silvente-Poirot, S, Simmonds, R, Simon, A, Simon, H, Simons, M, Singh, A, Singh, L, Singh, R, Singh, S, Sinha, D, Sinha, R, Sinha, S, Sirko, A, Sirohi, K, Sivridis, E, Skendros, P, Skirycz, A, Slaninová, I, Smaili, S, Smertenko, A, Smith, M, Soenen, S, Sohn, E, Sok, S, Solaini, G, Soldati, T, Soleimanpour, S, Soler, R, Solovchenko, A, Somarelli, J, Sonawane, A, Song, F, Song, H, Song, J, Song, K, Song, Z, Soria, L, Sorice, M, Soukas, A, Soukup, S, Sousa, D, Sousa, N, Spagnuolo, P, Spector, S, Srinivas Bharath, M, St Clair, D, Stagni, V, Staiano, L, Stalnecker, C, Stankov, M, Stathopulos, P, Stefan, K, Stefan, S, Stefanis, L, Steffan, J, Steinkasserer, A, Stenmark, H, Sterneckert, J, Stevens, C, Stoka, V, Storch, S, Stork, B, Strappazzon, F, Strohecker, A, Stupack, D, Su, H, Su, L, Suarez-Fontes, A, Subauste, C, Subbian, S, Subirada, P, Sudhandiran, G, Sue, C, Sui, X, Summers, C, Sun, G, Sun, J, Sun, K, Sun, M, Sun, Q, Sun, Y, Sun, Z, Sunahara, K, Sundberg, E, Susztak, K, Sutovsky, P, Suzuki, H, Sweeney, G, Symons, J, Sze, S, Szewczyk, N, Tabęcka-Łonczynska, A, Tabolacci, C, Tacke, F, Taegtmeyer, H, Tafani, M, Tagaya, M, Tai, H, Tait, S, Takahashi, Y, Takats, S, Talwar, P, Tam, C, Tam, S, Tampellini, D, Tamura, A, Tan, C, Tan, E, Tan, Y, Tanaka, M, Tang, D, Tang, J, Tang, T, Tanida, I, Tao, Z, Taouis, M, Tatenhorst, L, Tavernarakis, N, Taylor, A, Taylor, G, Taylor, J, Tchetina, E, Tee, A, Tegeder, I, Teis, D, Teixeira, N, Teixeira-Clerc, F, Tekirdag, K, Tencomnao, T, Tenreiro, S, Tepikin, A, Testillano, P, Tettamanti, G, Tharaux, P, Thedieck, K, Thekkinghat, A, Thellung, S, Thinwa, J, Thirumalaikumar, V, Thomas, S, Thomes, P, Thorburn, A, Thukral, L, Thum, T, Thumm, M, Tian, L, Tichy, A, Till, A, Timmerman, V, Titorenko, V, Todi, S, Todorova, K, Toivonen, J, Tomaipitinca, L, Tomar, D, Tomas-Zapico, C, Tomić, S, Tong, B, Tong, C, Tong, X, Tooze, S, Torgersen, M, Torii, S, Torres-López, L, Torriglia, A, Towers, C, Towns, R, Toyokuni, S, Trajkovic, V, Tramontano, D, Tran, Q, Travassos, L, Trelford, C, Tremel, S, Trougakos, I, Tsao, B, Tschan, M, Tse, H, Tse, T, Tsugawa, H, Tsvetkov, A, Tumbarello, D, Tumtas, Y, Tuñón, M, Turcotte, S, Turk, B, Turk, V, Turner, B, Tuxworth, R, Tyler, J, Tyutereva, E, Uchiyama, Y, Ugun-Klusek, A, Uhlig, H, Ułamek-Kozioł, M, Ulasov, I, Umekawa, M, Ungermann, C, Unno, R, Urbe, S, Uribe-Carretero, E, Üstün, S, Uversky, V, Vaccari, T, Vaccaro, M, Vahsen, B, Vakifahmetoglu-Norberg, H, Valdor, R, Valente, M, Valko, A, Vallee, R, Valverde, A, Van den Berghe, G, van der Veen, S, Van Kaer, L, van Loosdregt, J, van Wijk, S, Vandenberghe, W, Vanhorebeek, I, Vannier-Santos, M, Vannini, N, Vanrell, M, Vantaggiato, C, Varano, G, Varela-Nieto, I, Varga, M, Vasconcelos, M, Vats, S, Vavvas, D, Vega-Naredo, I, Vega-Rubin-de-Celis, S, Velasco, G, Velázquez, A, Vellai, T, Vellenga, E, Velotti, F, Verdier, M, Verginis, P, Vergne, I, Verkade, P, Verma, M, Verstreken, P, Vervliet, T, Vervoorts, J, Vessoni, A, Victor, V, Vidal, M, Vidoni, C, Vieira, O, Vierstra, R, Viganó, S, Vihinen, H, Vijayan, V, Vila, M, Vilar, M, Villalba, J, Villalobo, A, Villarejo-Zori, B, Villarroya, F, Villarroya, J, Vincent, O, Vindis, C, Viret, C, Viscomi, M, Visnjic, D, Vitale, I, Vocadlo, D, Voitsekhovskaja, O, Volonté, C, Volta, M, Vomero, M, Von Haefen, C, Vooijs, M, Voos, W, Vucicevic, L, Wade-Martins, R, Waguri, S, Waite, K, Wakatsuki, S, Walker, D, Walker, M, Walker, S, Walter, J, Wandosell, F, Wang, B, Wang, C, Wang, D, Wang, F, Wang, G, Wang, H, Wang, J, Wang, K, Wang, L, Wang, M, Wang, N, Wang, P, Wang, Q, Wang, W, Wang, X, Wang, Y, Wang, Z, Warnes, G, Warnsmann, V, Watada, H, Watanabe, E, Watchon, M, Wawrzyńska, A, Weaver, T, Wegrzyn, G, Wehman, A, Wei, H, Wei, L, Wei, T, Wei, Y, Weiergräber, O, Weihl, C, Weindl, G, Weiskirchen, R, Wells, A, Wen, R, Wen, X, Werner, A, Weykopf, B, Wheatley, S, Whitton, J, Whitworth, A, Wiktorska, K, Wildenberg, M, Wileman, T, Wilkinson, S, Willbold, D, Williams, B, Williams, R, Williamson, P, Wilson, R, Winner, B, Winsor, N, Witkin, S, Wodrich, H, Woehlbier, U, Wollert, T, Wong, E, Wong, J, Wong, R, Wong, V, Wong, W, Wu, A, Wu, C, Wu, J, Wu, K, Wu, M, Wu, S, Wu, W, Wu, X, Wu, Y, Xavier, R, Xia, H, Xia, L, Xia, Z, Xiang, G, Xiang, J, Xiang, M, Xiang, W, Xiao, B, Xiao, G, Xiao, H, Xiao, J, Xiao, L, Xiao, S, Xiao, Y, Xie, B, Xie, C, Xie, M, Xie, Y, Xie, Z, Xilouri, M, Xu, C, Xu, E, Xu, H, Xu, J, Xu, L, Xu, W, Xu, X, Xue, Y, Yakhine-Diop, S, Yamaguchi, M, Yamaguchi, O, Yamamoto, A, Yamashina, S, Yan, S, Yan, Z, Yanagi, Y, Yang, C, Yang, D, Yang, H, Yang, J, Yang, L, Yang, M, Yang, P, Yang, Q, Yang, S, Yang, W, Yang, X, Yang, Y, Yao, H, Yao, S, Yao, X, Yao, Y, Yasui, T, Yazdankhah, M, Yen, P, Yi, C, Yin, X, Yin, Y, Yin, Z, Ying, M, Ying, Z, Yip, C, Yiu, S, Yoo, Y, Yoshida, K, Yoshii, S, Yoshimori, T, Yousefi, B, Yu, B, Yu, H, Yu, J, Yu, L, Yu, M, Yu, S, Yu, V, Yu, W, Yu, Z, Yuan, J, Yuan, L, Yuan, S, Yuan, Y, Yuan, Z, Yue, J, Yue, Z, Yun, J, Yung, R, Zacks, D, Zaffagnini, G, Zambelli, V, Zanella, I, Zang, Q, Zanivan, S, Zappavigna, S, Zaragoza, P, Zarbalis, K, Zarebkohan, A, Zarrouk, A, Zeitlin, S, Zeng, J, Žerovnik, E, Zhan, L, Zhang, B, Zhang, D, Zhang, H, Zhang, J, Zhang, K, Zhang, L, Zhang, M, Zhang, P, Zhang, S, Zhang, W, Zhang, X, Zhang, Y, Zhang, Z, Zhao, H, Zhao, L, Zhao, S, Zhao, T, Zhao, X, Zhao, Y, Zheng, G, Zheng, K, Zheng, L, Zheng, S, Zheng, X, Zheng, Y, Zheng, Z, Zhivotovsky, B, Zhong, Q, Zhou, A, Zhou, B, Zhou, C, Zhou, G, Zhou, H, Zhou, J, Zhou, K, Zhou, R, Zhou, X, Zhou, Y, Zhou, Z, Zhu, B, Zhu, C, Zhu, G, Zhu, H, Zhu, W, Zhu, Y, Zhuang, H, Zhuang, X, Zientara-Rytter, K, Zimmermann, C, Ziviani, E, Zoladek, T, Zong, W, Zorov, D, Zorzano, A, Zou, W, Zou, Z, Zuryn, S, Zwerschke, W, Brand-Saberi, B, Kenchappa, C, Oshima, S, Rong, Y, Sluimer, J, and Stallings, C
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macroautophagy ,autophagy ,Autophagosome ,[SDV]Life Sciences [q-bio] ,cance ,LC3, macroautophagy ,autophagosome ,neurodegeneration ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Autophagy, Autophagosome ,NO ,stress vacuole ,stress ,autophagic processes ,stre ,rflux ,LC3 ,cancer ,guidelines ,flux ,lysosome ,phagophore ,vacuole ,Settore BIO/06 - Anatomia Comparata E Citologia ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,ComputingMilieux_MISCELLANEOUS ,Medaka oryzias latipes ,QH ,Autophagosome, cancer, flux, LC3, lysosome, macroautophagy, neurodegeneration, phagophore, stress vacuole ,Settore BIO/17 - ISTOLOGIA ,RC - Abstract
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field. doi: 10.1080/15548627.2020.1797280 ispartof: Autophagy vol:17 issue:1 pages:1-382 ispartof: location:United States status: published
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- 2021
15. Factors associated with lack of clinical improvement after vein ablation in the vascular quality initiative.
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Pinto Rodríguez P, Fassler M, Obi A, Osborne NH, Robinson ST, Jacobs BN, Aziz F, Nguyen KP, Gwozdz AM, Rodriguez LE, Fukaya E, Sachdev U, and Iyad Ochoa Chaar C
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- Humans, Male, Female, Retrospective Studies, Middle Aged, Aged, Treatment Outcome, Risk Factors, Varicose Veins surgery, Varicose Veins diagnostic imaging, Varicose Veins physiopathology, Databases, Factual, Severity of Illness Index, Chronic Disease, Adult, Patient Selection, Time Factors, Risk Assessment, Ablation Techniques adverse effects
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Background: Insurance companies have adopted variable and inconsistent approval criteria for chronic venous disease (CVD) treatment. Although vein ablation (VA) is accepted as the standard of care for venous ulcers, the treatment criteria for patients with milder forms of CVD remain controversial. This study aims to identify factors associated with a lack of clinical improvement (LCI) in patients with less severe CVD without ulceration undergoing VA to improve patient selection for treatment., Methods: We performed a retrospective analysis of patients undergoing VA for CEAP C2 to C4 disease in the Vascular Quality Initiative varicose veins database from 2014 to 2023. Patients who required intervention in multiple veins, had undergone prior interventions, or presented with CEAP C5 to C6 disease were excluded. The difference (Δ) in venous clinical severity score (VCSS; VCSS before minus after the procedure) was used to categorize the patients. Patients with a ΔVCSS of ≤0 were defined as having LCI after VA, and patients with ≥1 point decrease in the VCSS after VA (ΔVCSS ≥1) as having some benefit from the procedure and, therefore, "clinical improvement." The characteristics of both groups were compared, and multivariable regression analysis was performed to identify factors independently associated with LCI. A second analysis was performed based on the VVSymQ instrument, which measures patient-reported outcomes using five specific symptoms (ie, heaviness, achiness, swelling, throbbing pain, and itching). Patients with LCI showed no improvement in any of the five symptoms, and those with clinical improvement had a decrease in severity of at least one symptom., Results: A total of 3544 patients underwent initial treatment of CVD with a single VA. Of the 3544 patients, 2607 had VCSSs available before and after VA, and 420 (16.1%) had LCI based on the ΔVCSS. Patients with LCI were more likely to be significantly older and African American and have CEAP C2 disease compared with patients with clinical improvement. Patients with clinical improvement were more likely to have reported using compression stockings before treatment. The vein diameters were not different between the two groups. The incidence of complications was overall low, with minor differences between the two groups. However, the patients with LCI were significantly more likely to have symptoms after intervention than those with improvement. Patients with LCI were more likely to have technical failure, defined as vein recanalization. On multivariable regression, age (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00-1.02) and obesity (OR, 1.47; 95% CI, 1.09-2.00) were independently associated with LCI, as was treatment of less severe disease (CEAP C2; OR, 1.82; 95% CI, 1.30-2.56) compared with more advanced disease (C4). The lack of compression therapy before intervention was also associated with LCI (OR, 6.05; 95% CI, 4.30-8.56). The analysis based on the VVSymQ showed similar results., Conclusions: LCI after VA is associated with treating patients with a lower CEAP class (C2 vs C4) and a lack of compression therapy before intervention. Importantly, no significant association between vein size and clinical improvement was observed., Competing Interests: Disclosures None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2024
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16. Transcriptomic Profiling Identifies Ferroptosis-Related Gene Signatures in Ischemic Muscle Satellite Cells Affected by Peripheral Artery Disease-Brief Report.
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Tran L, Xie B, Assaf E, Ferrari R, Pipinos II, Casale GP, Mota Alvidrez RI, Watkins S, and Sachdev U
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- Humans, Transcriptome, Phospholipid Hydroperoxide Glutathione Peroxidase genetics, Phospholipid Hydroperoxide Glutathione Peroxidase metabolism, Lipid Peroxidation physiology, Iron metabolism, Ischemia, Ferroptosis genetics, Satellite Cells, Skeletal Muscle metabolism, Peripheral Arterial Disease genetics, Muscular Diseases
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Background: We hypothesized that transcriptomic profiling of muscle satellite cells in peripheral artery disease (PAD) would identify damage-related pathways contributing to skeletal muscle myopathy. We identified a potential role for ferroptosis-a form of programmed lytic cell death by iron-mediated lipid peroxidation-as one such pathway. Ferroptosis promotes myopathy in ischemic cardiac muscle but has an unknown role in PAD., Methods: Muscle satellite cells from donors with PAD were obtained during surgery. cDNA libraries were processed for single-cell RNA sequencing using the 10X Genomics platform. Protein expression was confirmed based on pathways inferred by transcriptomic analysis., Results: Unsupervised cluster analysis of over 25 000 cells aggregated from 8 donor samples yielded distinct cell populations grouped by a shared unique transcriptional fingerprint. Quiescent cells were diminished in ischemic muscle while myofibroblasts and apoptotic cells were prominent. Differential gene expression demonstrated a surprising increase in genes associated with iron transport and oxidative stress and a decrease in GPX4 (glutathione peroxidase 4) in ischemic PAD-derived cells. Release of the danger signal HMGB1 (high mobility group box-1) correlated with ferroptotic markers including surface transferrin receptor and were higher in ischemia. Furthermore, lipid peroxidation in muscle satellite cells was modulated by ferrostatin, a ferroptosis inhibitor. Histology confirmed iron deposition and lipofuscin, an inducer of ferroptosis in PAD-affected muscle., Conclusions: This report presents a novel finding that genes known to be involved in ferroptosis are differentially expressed in human skeletal muscle affected by PAD. Targeting ferroptosis may be a novel therapeutic strategy to reduce PAD myopathy., Competing Interests: Disclosures None.
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- 2023
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17. COVID-associated acute limb ischemia during the Delta surge and the effect of vaccines.
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Xie B, Semaan DB, Binko MA, Agrawal N, Kulkarni RN, Andraska EA, Sachdev U, Chaer RA, Eslami MH, Makaroun MS, and Sridharan N
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- Humans, Ischemia diagnostic imaging, Ischemia etiology, Ischemia therapy, Limb Salvage, Lower Extremity blood supply, Retrospective Studies, Risk Factors, SARS-CoV-2, Treatment Outcome, Vaccines, COVID-19 complications, Endovascular Procedures adverse effects, Peripheral Arterial Disease, COVID-19 Vaccines adverse effects
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Objective: Hypercoagulability is common in severe acute respiratory syndrome coronavirus 2 and has been associated with arterial thrombosis leading to acute limb ischemia (ALI). Our objective was to determine the outcomes of concurrent coronavirus disease 2019 (COVID-19) infection and ALI, particularly during the Delta variant surge and the impact of vaccination status., Methods: A retrospective review was performed of patients treated at a single health care system between March 2020 and December 2021 for ALI and recent (<14 days) COVID-19 infection or who developed ALI during hospitalization for the same disease. Patients were grouped by year as well as by pre and post Delta variant emergence in 2021 based on the World Health Organization timeline (January to May vs June to December). Baseline demographics, imaging, interventions, and outcomes were evaluated. A control cohort of all patients with ALI requiring surgical intervention for a 2-year period prior to the pandemic was used for comparison. Primary outcomes were in-hospital mortality and amputation-free survival. Kaplan-Meier survival and Cox proportional hazards analysis were performed., Results: Forty acutely ischemic limbs were identified in 36 patients with COVID-19, the majority during the Delta surge (52.8%) and after the wide availability of vaccines. The rate of COVID-19-associated ALI, although low overall, nearly doubled during the Delta surge (0.37% vs 0.20%; P = .09). Intervention (open or endovascular revascularization vs primary amputation) was performed on 31 limbs in 28 individuals, with the remaining eight treated with systemic anti-coagulation. Postoperative mortality was 48%, and overall mortality was 50%. Major amputation following revascularization was significantly higher with COVID-19 ALI (25% vs 3%; P = .006) compared with the pre-pandemic group. Thirty-day amputation-free survival was significantly lower (log-rank P < .001). COVID-19 infection (adjusted hazard ratio, 6.2; P < .001) and age (hazard ratio, 1.1; P = .006) were associated with 30-day amputation in multivariate analysis. Severity of COVID-19 infection, defined as vasopressor usage, was not associated with post-revascularization amputation. There was a higher incidence of re-thrombosis in the latter half of 2021 with the Delta surge, as reintervention for recurrent ischemia of the same limb was more common than our previous experience (21% vs 0%; P = .55). COVID-19-associated limb ischemia occurred almost exclusively in non-vaccinated patients (92%)., Conclusions: ALI observed with Delta appears more resistant to standard therapy. Unvaccinated status correlated highly with ALI occurrence in the setting of COVID-19 infection. Information of limb loss as a COVID-19 complication among non-vaccinated patients may help to increase compliance., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)
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- 2023
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18. Attenuated cell-cycle division protein 2 and elevated mitotic roles of polo-like kinase 1 characterize deficient myoblast fusion in peripheral arterial disease.
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Ferrari R, Cong G, Chattopadhyay A, Xie B, Assaf E, Morder K, Calderon MJ, Watkins SC, and Sachdev U
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- Cell Cycle, DNA, DNA Damage, Humans, Mitosis, Myoblasts metabolism, Protein Serine-Threonine Kinases, Proto-Oncogene Proteins, Polo-Like Kinase 1, CDC2 Protein Kinase metabolism, Cell Cycle Proteins metabolism, Peripheral Arterial Disease
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Introduction: We propose that MuSC-derived myoblasts in PAD have transcriptomic differences that can highlight underlying causes of ischemia-induced myopathy., Methods: Differentiation capacity among perfused and ischemic human myoblasts was compared. Following next generation sequencing of mRNA, Ingenuity Pathway Analysis (IPA) was performed for canonical pathway enrichment. Live cell imaging and immunofluorescence were performed to determine myocyte fusion index and protein expression based on insights from IPA, specifically concerning cell cycle regulators including cell-division cycle protein 2 (CDC2) and polo-like kinase 1 (PLK1)., Results: Ischemic myoblasts formed attenuated myotubes indicative of reduced fusion. Additionally, myoblasts from ischemic segments showed significant differences in canonical pathways associated with PLK1 (upregulated) and G2/M DNA damage checkpoint regulation (downregulated). PLK1 inhibition with BI2536 did not affect cell viability in any group over 24 h but deterred fusion more significantly in PAD myoblasts. Furthermore, PLK1 inhibition reduced the expression of checkpoint protein CDC2 in perfused but not ischemic cells., Conclusion: Differentiating myoblasts derived from ischemic muscle have significant differences in gene expression including those essential to DNA-damage checkpoint regulation and cell cycle progress. DNA-damage checkpoint dysregulation may contribute to myopathy in PAD., Competing Interests: Declaration of competing interest The authors of this paper have no conflicts of interest that affect this manuscript., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2022
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19. Inflammatory Caspase Activity Mediates HMGB1 Release and Differentiation in Myoblasts Affected by Peripheral Arterial Disease.
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Ferrari R, Xie B, Assaf E, Morder K, Scott M, Liao H, Calderon MJ, Ross M, Loughran P, Watkins SC, Pipinos I, Casale G, Tzeng E, McEnaney R, and Sachdev U
- Subjects
- Animals, Caspase 1 metabolism, Caspases metabolism, Inflammasomes metabolism, Ischemia, Mice, Myoblasts metabolism, RNA, Messenger metabolism, HMGB1 Protein, Peripheral Arterial Disease
- Abstract
Introduction: We previously showed that caspase-1 and -11, which are activated by inflammasomes, mediate recovery from muscle ischemia in mice. We hypothesized that similar to murine models, inflammatory caspases modulate myogenicity and inflammation in ischemic muscle disease. Methods: Caspase activity was measured in ischemic and perfused human myoblasts in response to the NLRP3 and AIM2 inflammasome agonists (nigericin and poly(dA:dT), respectively) with and without specific caspase-1 or pan-caspase inhibition. mRNA levels of myogenic markers and caspase-1 were assessed, and protein levels of caspases-1, -4, -5, and -3 were measured by Western blot. Results: When compared to perfused cells, ischemic myoblasts demonstrated attenuated MyoD and myogenin and elevated caspase-1 mRNA. Ischemic myoblasts also had significantly higher enzymatic caspase activity with poly(dA:dT) (p < 0.001), but not nigericin stimulation. Inhibition of caspase activity including caspase-4/-5, but not caspase-1, blocked activation effects of poly(dA:dT). Ischemic myoblasts had elevated cleaved caspase-5. Inhibition of caspase activity deterred differentiation in ischemic but not perfused myoblasts and reduced the release of HMGB1 from both groups. Conclusion: Inflammatory caspases can be activated in ischemic myoblasts by AIM2 and influence ischemic myoblast differentiation and release of pro-angiogenic HMGB1. AIM2 inflammasome involvement suggests a role as a DNA damage sensor, and our data suggest that caspase-5 rather than caspase-1 may mediate the downstream mediator of this pathway.
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- 2022
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20. Reply.
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Andraska EA and Sachdev U
- Published
- 2022
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21. Three cases of acute venous thromboembolism in females after vaccination for coronavirus disease 2019.
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Andraska EA, Kulkarni R, Chaudhary M, and Sachdev U
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- Adult, Aged, Aged, 80 and over, Computed Tomography Angiography, Female, Humans, Ultrasonography, Doppler, Venous Thromboembolism diagnosis, 2019-nCoV Vaccine mRNA-1273 adverse effects, COVID-19 prevention & control, SARS-CoV-2 immunology, Vaccination adverse effects, Venous Thromboembolism chemically induced
- Abstract
Since December 2020, four vaccines for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) have been developed, and three have been approved for immediate use in the United States. Two are mRNA vaccines, and one uses a viral vector mechanism. Thrombotic complications have been reported after vaccine administration, which were primarily cerebral sinus thromboses after administration of the viral vector vaccines. To the best of our knowledge, we are the first to report venous thrombotic complications within days of administration of the mRNA-1273 (Moderna) vaccine. We present a series of three women who developed venous thromboembolism after RNA-1273 vaccination at a single healthcare system., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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22. Elastic Laminar Reorganization Occurs with Outward Diameter Expansion during Collateral Artery Growth and Requires Lysyl Oxidase for Stabilization.
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McEnaney RM, McCreary DD, Skirtich NO, Andraska EA, Sachdev U, and Tzeng E
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- Animals, Arteries diagnostic imaging, Collagen metabolism, Extracellular Matrix metabolism, Humans, Male, Organogenesis, Rats, Sprague-Dawley, Tomography, X-Ray Computed, Vascular Remodeling, Rats, Arteries enzymology, Arteries growth & development, Elasticity, Protein-Lysine 6-Oxidase metabolism
- Abstract
When a large artery becomes occluded, hemodynamic changes stimulate remodeling of arterial networks to form collateral arteries in a process termed arteriogenesis. However, the structural changes necessary for collateral remodeling have not been defined. We hypothesize that deconstruction of the extracellular matrix is essential to remodel smaller arteries into effective collaterals. Using multiphoton microscopy, we analyzed collagen and elastin structure in maturing collateral arteries isolated from ischemic rat hindlimbs. Collateral arteries harvested at different timepoints showed progressive diameter expansion associated with striking rearrangement of internal elastic lamina (IEL) into a loose fibrous mesh, a pattern persisting at 8 weeks. Despite a 2.5-fold increase in luminal diameter, total elastin content remained unchanged in collaterals compared with control arteries. Among the collateral midzones, baseline elastic fiber content was low. Outward remodeling of these vessels with a 10-20 fold diameter increase was associated with fractures of the elastic fibers and evidence of increased wall tension, as demonstrated by the straightening of the adventitial collagen. Inhibition of lysyl oxidase (LOX) function with β-aminopropionitrile resulted in severe fragmentation or complete loss of continuity of the IEL in developing collaterals. Collateral artery development is associated with permanent redistribution of existing elastic fibers to accommodate diameter growth. We found no evidence of new elastic fiber formation. Stabilization of the arterial wall during outward remodeling is necessary and dependent on LOX activity.
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- 2021
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23. Inflammatory signals and network connections implicate cell-mediated immunity in chronic venous insufficiency.
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Vodovotz L, Zamora R, Barclay DA, Vodovotz Y, Yin J, Bitner J, Florida J, Avgerinos ED, and Sachdev U
- Abstract
Background: The role of inflammation in superficial venous reflux in varicose veins (VVs) is unknown. Computational network modeling has deduced inflammation in experimental and clinical settings. We measured immune mediators in plasma from competent and incompetent leg veins inferring the role of cellular immunity based on cytokine networks., Methods: Temperature was assessed using infrared thermography (IRT) to measure inflammation. Blood was obtained during sclerotherapy or endovenous thermal ablation for VVs. Control subjects underwent phlebotomy from saphenous and forearm veins. Vein segments were harvested during surgery. Demographics, clinical, etiology, anatomy and pathophysiology classification, venous clinical severity scores (VCSSs), and body mass index (BMI) were collected. Twenty-five mediators were measured in serum and vein segments. Means were compared using Mann-Whitney U test. Pearson correlations equaling or exceeding a threshold prompted connections among nodes, and mapped as networks. Spearman correlations were performed between interleukin (IL)-17A and both granulocyte macrophage colony stimulation factor, and IL-10 as indicators of pathogenic and nonpathogenic Th17 cell involvement., Results: Age, BMI, and VCSSs differed significantly between groups. Temperatures were higher over diseased veins. Plasma concentrations of 20 cytokines differed between control and patient subjects (P<0.05), and most were lower in patients. C-X-C motif chemokine ligand-9 (aka monokine-induced by gamma interferon), C-X-C motif chemokine ligand 10 (aka IFNγ induced protein 10), and soluble IL-2 receptor-alpha were higher in patients, but not connected to other mediators in networks. In contrast, IL-17A, IL-12p70, and interferon gamma were the only mediators that were more highly interconnected in venous insufficiency. IL-17A and granulocyte macrophage colony stimulating factor (GM-CSF) were highly correlated in chronic venous insufficiency (CVI) but not in controls. In tissue, refluxing VVs significantly higher IL-15 expression than competent saphenous veins., Conclusions: Venous insufficiency associates with age, BMI, skin temperature, and plasma cytokines associated with interferon gamma and possibly IL-17A signaling. The vein wall may be a source of activation of cellular activation, given elevated IL-15 expression. Correlations between IL-17A and GM-CSF suggested a potential role for pathogenic Th17 cells in VVs. Differentially expressed inflammatory networks induced by venous hypertension may reflect or drive venous damage and ulceration., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-688). YV serves as an unpaid editorial board member of Annals of Translational Medicine from March 2019 to February 2021. YV serves on the board of directors of the Society for Complex Acute Illness and is a co-founder of, and stakeholder in Immunetrics Inc., Pittsburgh, PA, USA. Neither of these relationships had any impact on the work presented in this manuscript. US reports this work supported by the SVS Foundation. The other authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)
- Published
- 2021
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24. Linguistic Analysis of Letters of Recommendation for Vascular Surgery and Obstetrics and Gynecology Applicants Detects Differences in Attributable Strengths Based on Gender.
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Go C, Lang S, Byrne M, Brucha DL, Parviainen K, and Sachdev U
- Subjects
- Cross-Sectional Studies, Female, Humans, Linguistics, Male, Personnel Selection, Sexism, Gynecology, Internship and Residency, Obstetrics
- Abstract
Objective: We asked whether letters of recommendation (LOR) written for applicants to vascular surgery (VS), a field where men have traditionally predominated, differentially highlight attributes based on applicant gender. For comparison, LOR for applicants to Obstetrics and Gynecology (Ob/Gyn), a surgical field where women are highly represented were evaluated., Design: We performed a cross-sectional review of LORs for students applying to VS or Ob/Gyn at our institution from 2017 to2018. Blinded to the gender of both the applicant and the letter author, investigators assessed word count per letter and used published rubrics to quantify how many words in the following categories: communal ("friendly"), able ("competent"), standout ("exceptional"), and grindstone ("hardworking"). Frequencies were reported as a function of specialty and gender., Setting: The study was performed at the University of Pittsburgh Medical Center and included letters written for applicants only to the stated residency programs at University of Pittsburgh Medical Center., Participants: LOR written for self-identified women and men applying to both residencies from US-based allopathic medical schools were de-identified and evaluated by blinded reviewers., Results: One hundred and ninety-eight letters were reviewed for vascular surgery applicants. Two hundred letters were randomly selected from applications to Ob/Gyn as a comparison. Fifty-four vascular (27.8% women) and 63 Ob/Gyn (77.8% women) applicants were reviewed (p < 0.001 for gender). Licensing exam scores were higher for women than men applying to Ob/Gyn. Honor status was similar across fields and gender. Letters were shorter for VS applicants (p = 0.04). Gender-specific words (i.e., "lady" or "gentleman") were used more in VS letters (0.24 ± 0.50 vs 0.14 ± 0.42, p = 0.048). Ability words were more common (4.7 ± 2.6 vs 3.8 ± 2.1, p = 0.028) and grindstone adjectives were less common (3.4 ± 2.3 vs 4.5 ± 3.1, p = 0.024) in letters written for women compared to men VS applicants. Twenty-nine letters written for students applying to VS had honors status. While none written for women mentioned this achievement, 43% of those written for men did (p < 0.05). Letters for women applicants to Ob/Gyn contained more standout adjectives than those written for men (2.12 ± 2.2 vs 1.39 ± 1.25, p = 0.021)., Conclusions: Reference letters for both specialties highlighted attributes differently depending on the gender of the applicant. Although this likely represents an unconscious process, care should be taken to limit potential biases in LOR which are "gatekeepers" to access and advancement., (Copyright © 2021 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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25. Health care disparities during the COVID-19 pandemic.
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Andraska EA, Alabi O, Dorsey C, Erben Y, Velazquez G, Franco-Mesa C, and Sachdev U
- Subjects
- Healthcare Disparities, Humans, SARS-CoV-2, United States epidemiology, COVID-19, Pandemics
- Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is a pandemic with more than 32 million cases and more than 500,000 deaths nationwide. With the significant health consequences seen secondary to COVID-19, health care disparities have been further exacerbated. Mechanisms that have been proposed to account for the increased disparity seen during the COVID-19 pandemic are multifactorial. This review of the literature outlines the unique barriers to health and disparities that are associated with vulnerable communities who have been most impacted by the COVID-19 pandemic in the United States., (Copyright © 2021. Published by Elsevier Inc.)
- Published
- 2021
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26. Letters of recommendation: Nuanced bias or useful affirmation?
- Author
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Go C and Sachdev U
- Subjects
- Cultural Diversity, Humans, Race Factors, Racism, Sex Factors, Sexism, Correspondence as Topic, Education, Medical, Graduate, Fellowships and Scholarships, Internship and Residency, Personnel Selection, Physicians, Women, Prejudice, School Admission Criteria, Social Discrimination, Surgeons education
- Abstract
Narrative letters of recommendation (NLORs) have become key elements of the application process for residency and fellowship. The potential to inadvertently admit bias into these subjective narratives has become an area of research focus across many disciplines. In the present review, we have highlighted the current data regarding bias in NLORs. We also believe that one of the most effective methods to eliminate bias from written recommendations is to first understand that it exists. Thus, the objective measures that have been taken to identify bias in NLORs are important steps in the right direction. We have presented and reflected on the accrued data on bias in NLORs pertaining to surgical training., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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27. Invited commentary.
- Author
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Sachdev U
- Published
- 2021
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28. Fibrosis Distinguishes Critical Limb Ischemia Patients from Claudicants in a Transcriptomic and Histologic Analysis.
- Author
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Cong G, Cui X, Ferrari R, Pipinos II, Casale GP, Chattopadhyay A, and Sachdev U
- Abstract
Most patients with critical limb ischemia (CLI) from peripheral arterial disease (PAD) do not have antecedent intermittent claudication (IC). We hypothesized that transcriptomic analysis would identify CLI-specific pathways, particularly in regards to fibrosis. Derivation cohort data from muscle biopsies in PAD and non-PAD (controls) was obtained from the Gene Expression Omnibus (GSE120642). Transcriptomic analysis indicated CLI patients (N = 16) had a unique gene expression profile, when compared with non-PAD controls (N = 15) and IC (N = 20). Ninety-eight genes differed between controls and IC, 2489 genes differed between CLI and controls, and 2783 genes differed between CLI and IC patients. Pathway enrichment analysis showed that pathways associated with TGFβ, collagen deposition, and VEGF signaling were enriched in CLI but not IC. Receiver operating curve (ROC) analysis of nine fibrosis core gene expression revealed the areas under the ROC (AUC) were all >0.75 for CLI. Furthermore, the fibrosis area (AUC = 0.81) and % fibrosis (AUC = 0.87) in validation cohort validated the fibrosis discrimination CLI from IC and control (all n = 12). In conclusion, transcriptomic analysis identified fibrosis pathways, including those involving TGFβ, as a novel gene expression feature for CLI but not IC. Fibrosis is an important characteristic of CLI, which we confirmed histologically, and may be a target for novel therapies in PAD., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
- Published
- 2020
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29. Low serum vitamin C correlates with an increased risk of peripheral arterial disease in current smokers: Results from NHANES 2003-2004.
- Author
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Cong G, Yan R, and Sachdev U
- Abstract
Background: Cigarette smoking is one of the most critical risk factors for peripheral arterial disease (PAD) and inversely correlated Vitamin C. Here we determine whether serum vitamin C correlates with the risk of PAD, especially among current smokers., Methods: A cross-sectional analysis of 2383 individuals ≥40 y was performed from the U.S. National Health and Nutrition Examination Survey (NHANES 2003-2004), including measurement of ankle-brachial index (ABI), smoking status and serum vitamin C. We examined the interactions between plasma vitamin C and exposure to smoking on the risk of PAD., Results: 912 (38.2%) were current smokers while 207 participants were diagnosed with PAD based on ABI(ABI≤0.9). Current smokers in the lowest vitamin C quartile had the highest prevalence of PAD (14.1%) compared to other quartiles. However, this trend was not significant in nonsmokers. Current smokers in the lowest quartile had a 2.32-fold risk (95% CI, 1.03-5.32; P = 0.04) for PAD after weighted adjustment for potential confounders, including vitamin D and C-reactive protein. In contrast, non-smokers did not have a differing risk of PAD as a function of vitamin C (P for interaction = 0.019)., Conclusions: As an anti-oxidant and anti-inflammatory, low serum vitamin C appears to associates with the risk of PAD in smokers. A relationship between PAD and vitamin C in non-current smokers is not apparent. Modulating vitamin C in current smokers may help mitigate the risk of PAD and should be a target of mechanistic study., Competing Interests: Declaration of Competing Interest None declared.
- Published
- 2020
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30. Caspase1/11 signaling affects muscle regeneration and recovery following ischemia, and can be modulated by chloroquine.
- Author
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Sachdev U, Ferrari R, Cui X, Pius A, Sahu A, Reynolds M, Liao H, Sun P, Shinde S, Ambrosio F, Shiva S, Loughran P, and Scott M
- Subjects
- Animals, Autophagosomes metabolism, Autophagy drug effects, Betacoronavirus, COVID-19, Coronavirus Infections drug therapy, Glycolysis physiology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Microtubule-Associated Proteins metabolism, Muscle Cells metabolism, Muscle Development, Muscle, Skeletal metabolism, Neovascularization, Physiologic, Oxidative Phosphorylation, Pandemics, Peripheral Arterial Disease pathology, Pneumonia, Viral drug therapy, Regeneration, SARS-CoV-2, Signal Transduction, COVID-19 Drug Treatment, Caspase 1 metabolism, Caspases, Initiator metabolism, Chloroquine pharmacology, Coronavirus Infections pathology, Ischemia pathology, Muscle, Skeletal pathology, Pneumonia, Viral pathology
- Abstract
Background: We previously showed that the autophagy inhibitor chloroquine (CQ) increases inflammatory cleaved caspase-1 activity in myocytes, and that caspase-1/11 is protective in sterile liver injury. However, the role of caspase-1/11 in the recovery of muscle from ischemia caused by peripheral arterial disease is unknown. We hypothesized that caspase-1/11 mediates recovery in muscle via effects on autophagy and this is modulated by CQ., Methods: C57Bl/6 J (WT) and caspase-1/11 double-knockout (KO) mice underwent femoral artery ligation (a model of hind-limb ischemia) with or without CQ (50 mg/kg IP every 2nd day). CQ effects on autophagosome formation, microtubule associated protein 1A/1B-light chain 3 (LC3), and caspase-1 expression was measured using electron microscopy and immunofluorescence. Laser Doppler perfusion imaging documented perfusion every 7 days. After 21 days, in situ physiologic testing in tibialis anterior muscle assessed peak force contraction, and myocyte size and fibrosis was also measured. Muscle satellite cell (MuSC) oxygen consumption rate (OCR) and extracellular acidification rate was measured. Caspase-1 and glycolytic enzyme expression was detected by Western blot., Results: CQ increased autophagosomes, LC3 consolidation, total caspase-1 expression and cleaved caspase-1 in muscle. Perfusion, fibrosis, myofiber regeneration, muscle contraction, MuSC fusion, OCR, ECAR and glycolytic enzyme expression was variably affected by CQ depending on presence of caspase-1/11. CQ decreased perfusion recovery, fibrosis and myofiber size in WT but not caspase-1/11KO mice. CQ diminished peak force in whole muscle, and myocyte fusion in MuSC and these effects were exacerbated in caspase-1/11KO mice. CQ reductions in maximal respiration and ATP production were reduced in caspase-1/11KO mice. Caspase-1/11KO MuSC had significant increases in protein kinase isoforms and aldolase with decreased ECAR., Conclusion: Caspase-1/11 signaling affects the response to ischemia in muscle and effects are variably modulated by CQ. This may be critically important for disease treated with CQ and its derivatives, including novel viral diseases (e.g. COVID-19) that are expected to affect patients with comorbidities like cardiovascular disease.
- Published
- 2020
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31. The VE-PTP Inhibitor AKB-9778 Improves Antitumor Activity and Diminishes the Toxicity of Interleukin 2 (IL-2) Administration.
- Author
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Li G, Sachdev U, Peters K, Liang X, and Lotze MT
- Subjects
- Aniline Compounds therapeutic use, Animals, Antineoplastic Agents therapeutic use, Cell Line, Tumor, Cytokines blood, Cytokines metabolism, Disease Models, Animal, Drug Synergism, Female, Gene Expression, Genes, Reporter, Humans, Inflammation Mediators, Interleukin-2 adverse effects, Liver Neoplasms drug therapy, Liver Neoplasms pathology, Liver Neoplasms secondary, Mice, Sulfonic Acids therapeutic use, Xenograft Model Antitumor Assays, Aniline Compounds pharmacology, Antineoplastic Agents pharmacology, Interleukin-2 administration & dosage, Receptor-Like Protein Tyrosine Phosphatases, Class 3 antagonists & inhibitors, Sulfonic Acids pharmacology
- Abstract
Administration of interleukin (IL)-2 has led to a durable response in patients with advanced renal cancer and melanoma but is restricted for clinical application because of adverse effects, including the vascular leak syndrome (VLS). VLS is associated with increased circulating levels of the Tie2 antagonist ligand, angiopoietin 2, and decreased Tie2 receptor phosphorylation and downstream signaling in endothelial cells (ECs). Given that vascular endothelial protein tyrosine phosphatase (VE-PTP) is a specific membrane phosphatase in ECs that dephosphorylates Tie2, the effects of targeting VE-PTP by a selective inhibitor AKB-9778 (AKB) in terms of VLS and antitumor efficacy were examined in this study. The authors found, by targeting VE-PTP, that the antitumor effects induced by IL-2 were augmented [tumor-free 44% (IL-2 alone) vs. 87.5% (IL-2+AKB)], associated with enhanced immune cell infiltrate (90% increase for CD8 T cells and natural killer cells). In addition, the side effects of IL-2 therapy were lessened, as demonstrated by diminished lung weight (less vascular leakage) as well as reduced cytokine levels (serum HMGB1 from 137.04±2.69 to 43.86±3.65 pg/mL; interferon-γ from 590.52±90.52 to 31.37±1.14 pg/mL). The authors further sought to determine the potential mechanism of the action of AKB-9778. The findings suggest that AKB-9778 may function through reducing serum angiopoietin 2 level and regulating EC viability. These findings provide insights into the targeting VE-PTP to improve tolerance and efficacy of IL-2 therapy and highlight the clinical potential of AKB-9778 for treating patients with VLS and cancer.
- Published
- 2019
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32. Standardized care protocol and modifications to electronic medical records to facilitate venous ulcer healing.
- Author
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Bitner J, Sachdev U, Hager ES, and Dillavou ED
- Subjects
- Adult, Aged, Aged, 80 and over, Chronic Disease, Databases, Factual, Female, Health Communication, Health Status, Humans, Male, Middle Aged, Patient Education as Topic, Pennsylvania, Pilot Projects, Retrospective Studies, Risk Reduction Behavior, Smoking Cessation, Time Factors, Treatment Outcome, Varicose Ulcer diagnosis, Varicose Ulcer physiopathology, Weight Loss, Clinical Protocols standards, Electronic Health Records standards, Varicose Ulcer therapy, Wound Healing
- Abstract
Background: Venous ulcers are painful, recurrent, and difficult to heal. Electronic medical records (EMRs) are often not optimized to track wounds. Specialized wound care programs may not interface with office-based records, creating a need to standardize the process of venous ulcer measurement and dressing documentation within existing systems. This work describes the creation of an EMR protocol to track venous ulcer size, to standardize dressings, to address related health issues, and to improve education of the patient. We hypothesized that the institution of an EMR protocol to track clinical features of venous ulcer patients, including wound size and health status, would facilitate wound healing., Methods: We performed a retrospective review of a prospective database from September 2014 to May 2017. Modifications to the EMR included the formation of a venous ulcer patient list, a dressing tracker, calculation of total ulcer area, graphing of ulcer size over time, and images of the wound area. Patient education materials were created through the EMR and loaded into an automatic end-visit printout that emphasized smoking cessation, weight loss, and consultation with specialty services as necessary. Quarterly meetings with the supervising physician were established to review each patient's wound progress and to target areas of improvement., Results: During the study period, 204 patients with chronic C5 and C6 disease were observed. Before the start of the project, the healing rate was 53.3%. Wound healing rates improved from 59.5% (quarter 1) to 77.94% (quarter 8). In the quarter before the project started, there were no patients who had quit or cut down on smoking or smokeless tobacco, no patients who were referred for weight loss consultation, and nine who were already patients of bariatric surgery. During the study period, 29% of patients quit smoking, 19% decreased smoking, and 20% cut down smokeless tobacco use. There were 54 patients who underwent advanced arterial evaluation; 175 patients underwent sclerotherapy and 137 patients had endovenous thermal ablation to treat axial reflux in the affected limb. The EMR modification project took 13 months to craft and to implement, with approximately 8 hours of meeting time from the surgical team., Conclusions: A comprehensive care model for venous ulcer patients through EMR modification improved overall patient care, increased communication between providers, and facilitated ulcer healing. EMR modification can be introduced with an acceptable time investment on the part of both the provider and the institutional information technology team., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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33. TLR4-dependent upregulation of the platelet NLRP3 inflammasome promotes platelet aggregation in a murine model of hindlimb ischemia.
- Author
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Vogel S, Murthy P, Cui X, Lotze MT, Zeh HJ 3rd, and Sachdev U
- Subjects
- Animals, Inflammasomes blood, Ischemia blood, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, NLR Family, Pyrin Domain-Containing 3 Protein blood, NLR Family, Pyrin Domain-Containing 3 Protein deficiency, Platelet Activation, Platelet Aggregation, Signal Transduction, Toll-Like Receptor 4 blood, Up-Regulation, Disease Models, Animal, Hindlimb metabolism, Inflammasomes metabolism, Ischemia metabolism, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Toll-Like Receptor 4 metabolism
- Abstract
Platelets play a critical role in the pathophysiology of peripheral arterial disease (PAD). The mechanisms by which muscle ischemia regulates aggregation of platelets are poorly understood. We have recently identified the Nod-like receptor nucleotide-binding domain leucine rich repeat containing protein 3 (NLRP3) expressed by platelets as a critical regulator of platelet activation and aggregation, which may be triggered by activation of toll-like receptor 4 (TLR4). In this study, we performed femoral artery ligation (FAL) in transgenic mice with platelet-specific ablation of TLR4 (TLR4 PF4) and in NLRP3 knockout (NLRP3
-/- ) mice. NLRP3 inflammasome activity of circulating platelets, as monitored by activation of caspase-1 and cleavage of interleukin-1β (IL-1β), was upregulated in mice subjected to FAL. Genetic ablation of TLR4 in platelets led to decreased platelet caspase 1 activation and platelet aggregation, which was reversed by the NLRP3 activator Nigericin. Two weeks after the induction of FAL, ischemic limb perfusion was increased in TLR4 PF4 and NLRP3-/- mice as compared to control mice. Hence, activation of platelet TLR4/NLRP3 signaling plays a critical role in upregulating platelet aggregation and interfering with perfusion recovery in muscle ischemia and may represent a therapeutic target to improve limb salvage., (Copyright © 2018 Elsevier Inc. All rights reserved.)- Published
- 2019
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34. Invited commentary.
- Author
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Sachdev U
- Subjects
- Angiotensin II, Humans, NF-kappa B, Polysaccharides, Aortic Aneurysm, Abdominal, JNK Mitogen-Activated Protein Kinases
- Published
- 2018
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35. Suppressed networks of inflammatory mediators characterize chronic venous insufficiency.
- Author
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Sachdev U, Vodovotz L, Bitner J, Barclay D, Zamora R, Yin J, Simmons RL, and Vodovotz Y
- Subjects
- Adult, Biomarkers blood, Blood Specimen Collection methods, Case-Control Studies, Chronic Disease, Female, Humans, Inflammation blood, Inflammation complications, Inflammation Mediators blood, Male, Middle Aged, Pilot Projects, Principal Component Analysis, Prospective Studies, Signal Transduction physiology, Venous Insufficiency blood, Venous Insufficiency etiology, Inflammation Mediators physiology, Venous Insufficiency physiopathology
- Abstract
Objective: Chronic venous insufficiency (CVI) affects 25 million adults in the United States. Little emphasis has been placed on inflammatory changes associated with CVI. We hypothesize that in patients with early to mid-stage benign varicose vein disease, differences in circulating inflammatory mediators will be manifested in blood draining the involved area vs circulating blood in control subjects., Methods: Patients undergoing either endovenous ablation or sclerotherapy for Clinical, Etiology, Anatomy, and Pathophysiology clinical class 3 to 5 disease underwent phlebotomy from regional veins at the time of the procedure. The patient's age, gender, clinical class, duration of symptoms, presence of superficial truncal reflux by duplex ultrasound, and treatment modality were recorded. Plasma from patients and banked blood samples from healthy volunteers (HVs) were subjected to Luminex (EMD Millipore, Billerica, Mass) to evaluate the expression of an established panel of 20 inflammatory mediators. Mediator concentrations were compared between patients and HVs using Mann-Whitney U tests. Importantly, computational analysis allowed us to compare not only the panel of inflammatory mediators but also the inflammatory networks connecting these mediators to one another. Principal components were analyzed to assess network robustness in each group., Results: CVI venous blood revealed significantly lower levels of monokine induced by γ interferon, soluble interleukin (IL) 2 receptor α chain, IL-4, IL-6, IL-7, tumor necrosis factor α, eotaxin, and granulocyte-macrophage colony-stimulating factor than blood from controls. Inflammatory networks were significantly less complex and less robust in the CVI patients compared with HVs. Based on principal component analysis, responses among HVs were more varied than those of CVI patients., Conclusions: We demonstrate that patients with CVI have significant differences not only in blood-borne inflammatory mediators but also in the interconnectedness of these mediators with one another and in their principal inflammatory characteristics. Results suggest hypoinflammation in chronic nonhealing changes in CVI. These novel findings, if validated in larger cohorts, may help predict the risk of disease progression or response to therapy in the future and may guide mechanistic studies on tissue responses to CVI., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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36. Chloroquine improves the response to ischemic muscle injury and increases HMGB1 after arterial ligation.
- Author
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Xu J, Cui X, Li J, Koutakis P, Pipinos I, Tzeng E, Chen A, and Sachdev U
- Subjects
- Aged, Animals, Autophagy drug effects, Blood Flow Velocity, Case-Control Studies, Caspase 1 metabolism, Cell Line, Disease Models, Animal, Female, HMGB1 Protein deficiency, HMGB1 Protein genetics, Humans, Intermittent Claudication metabolism, Intermittent Claudication pathology, Ischemia metabolism, Ischemia pathology, L-Lactate Dehydrogenase metabolism, Ligation, Male, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Muscle, Skeletal metabolism, Muscle, Skeletal pathology, Peripheral Arterial Disease metabolism, Peripheral Arterial Disease pathology, Recovery of Function, Regional Blood Flow, Sequestosome-1 Protein metabolism, Signal Transduction drug effects, Up-Regulation, Chloroquine pharmacology, Femoral Artery surgery, HMGB1 Protein metabolism, Intermittent Claudication drug therapy, Ischemia drug therapy, Muscle, Skeletal blood supply, Muscle, Skeletal drug effects, Peripheral Arterial Disease drug therapy
- Abstract
Objective: We have previously shown that exogenous administration of the nuclear protein high mobility group box 1 (HMGB1) improves angiogenesis after tissue ischemia. Antagonizing HMGB1 prolongs muscle necrosis and deters regeneration. In this study, we evaluated HMGB1 expression in peripheral arterial disease (PAD) and the mechanisms that promote its release in a murine model of hindlimb ischemia. Specifically, we investigated how chloroquine (CQ), a commonly employed disease-modifying antirheumatic drug, promotes HMGB1 release from muscle. We hypothesized that CQ could increase HMGB1 locally and systemically, allowing it to mediate recovery from ischemic injury., Methods: Muscle biopsies were performed on patients undergoing lower extremity surgery for non-PAD-related disease as well as for claudication and critical limb ischemia. Clinical symptoms and ankle-brachial indices were recorded for each patient. HMGB1 was detected in muscle sections using immunohistochemical staining. Unilateral femoral artery ligation was performed on both wild-type and inducible HMGB1 knockout mice. Wild-type mice were administered intraperitoneal CQ 2 weeks before and after femoral artery ligation. Laser Doppler perfusion imaging was used to determine perfusion recovery. Serum and tissue levels of HMGB1 were measured at designated time points. In vitro, cultured C2C12 myoblasts were treated with increasing doses of CQ. HMGB1, autophagosome formation, p62/SQSTM1 accumulation, caspase-1 expression and activity, and lactate dehydrogenase levels were measured in supernatants and cell lysates., Results: Nuclear expression of HMGB1 was prominent in patients with claudication and critical limb ischemia (P < .05) compared with controls. CQ-treated mice had elevated serum HMGB1 and diffuse HMGB1 staining in muscle (P < .01). In wild-type mice, CQ treatment resulted in higher laser Doppler perfusion imaging ratios in the ischemic limb at 7 days (P < .03) and less fat replacement after 2 weeks (P < .03). In cultured myoblasts, CQ induced autophagosome accumulation, inhibited p62/SQSTM-1 degradation, and activated caspase-1., Conclusions: HMGB1 is prominently expressed in PAD muscle but mostly confined to the nucleus. Our in vivo data suggest that HMGB1 mobilization into the sarcoplasm and serum can be increased with CQ, possibly through caspase-1-mediated pathways. Whereas HMGB1 can be released by many cell types, these studies suggest that the muscle may be an important additional source that is relevant in PAD., (Copyright © 2017 Society for Vascular Surgery. All rights reserved.)
- Published
- 2018
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37. Cephalic vein transposition is a durable approach to managing cephalic arch stenosis.
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Henry JC, Sachdev U, Hager E, Dillavou E, Yuo T, Makaroun M, and Leers SA
- Abstract
Introduction: The proximal cephalic vein that enters the axillary vein (cephalic arch) is a common site of stenosis in patients with upper extremity arteriovenous fistulas for hemodialysis (HD). In this study, we present the outcomes of a series of cephalic vein transposition, to determine its utility in the setting of refractory arch stenosis., Methods: We conducted a retrospective review of patients undergoing cephalic vein transposition to manage refractory cephalic arch stenosis from January 1, 2008 to August 31, 2015. Demographics, past medical history, access history of the patients as well as procedural details of the surgery to the stenotic segment, patency of the access, and the need for subsequent interventions were recorded., Results: Twenty-three patients underwent a cephalic vein transposition during the study period. The patients undergoing cephalic transposition had their current access for an average of 3.0 ± 2.6 years and had an average of 2.3 ± 0.9 interventions on the access prior to the surgery. Complications from the surgery were uncommon (8.7%) and no patient required a temporary tunneled dialysis catheter. The re-intervention rate was 0.2 ± 0.2 interventions per patient per year. At two years, primary patency was 70.9% and cumulative patency was 94.7% for the patients with cephalic transposition., Conclusions: Cephalic vein transposition is safe and effective treatment for cephalic arch stenosis without interrupting utilization of the access. The surgical approach to stenosis of the proximal cephalic vein is effective, requires minimal re-interventions, and should be considered for isolated, refractory cephalic arch stenosis in mature arteriovenous fistulas.
- Published
- 2017
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38. Perpetual change: autophagy, the endothelium, and response to vascular injury.
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Sachdev U and Lotze MT
- Subjects
- Animals, Humans, Autophagy physiology, Endothelium, Vascular pathology, Vascular System Injuries pathology
- Abstract
Current studies of vascular health, aging, and autophagy emphasize how the endothelium adapts to stress and contributes to disease. The endothelium is far from an inert barrier to blood-borne cells, pathogens, and chemical signals; rather, it actively translates circulating mediators into tissue responses, changing rapidly in response to physiologic stressors. Macroautophagy-the cellular ingestion of effete organelles and protein aggregates to provide anabolic substrates to fuel bioenergetics in times of stress-plays an important role in endothelial cell homeostasis, vascular remodeling, and disease. These roles include regulating vascular tone, sustaining or limiting cell survival, and contributing to the development of atherosclerosis secondary to infection, inflammation, and angiogenesis. Autophagy modulates these critical functions of the endothelium in a dynamic and perpetual response to tissue and intravascular cues., (© Society for Leukocyte Biology.)
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- 2017
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39. The NLRP3 inflammasome and bruton's tyrosine kinase in platelets co-regulate platelet activation, aggregation, and in vitro thrombus formation.
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Murthy P, Durco F, Miller-Ocuin JL, Takedai T, Shankar S, Liang X, Liu X, Cui X, Sachdev U, Rath D, Lotze MT, Zeh HJ 3rd, Gawaz M, Weber AN, and Vogel S
- Subjects
- Agammaglobulinaemia Tyrosine Kinase, Animals, Benzamides pharmacology, Bridged Bicyclo Compounds, Heterocyclic pharmacology, Cells, Cultured, Humans, Interleukin-1beta metabolism, Mice, Inbred CBA, Mice, Knockout, NLR Family, Pyrin Domain-Containing 3 Protein genetics, Nigericin pharmacology, Platelet Activation drug effects, Platelet Aggregation drug effects, Platelet Aggregation physiology, Protein-Tyrosine Kinases genetics, Inflammasomes metabolism, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Platelet Activation physiology, Protein-Tyrosine Kinases metabolism, Thrombosis metabolism
- Abstract
Cleavage of interleukin-1β (IL-1β) is a key inflammatory event in immune cells and platelets, which is mediated by nucleotide-binding domain leucine rich repeat containing protein (NLRP3)-dependent activation of caspase-1. In immune cells, NLRP3 and caspase-1 form inflammasome complexes with the adaptor proteins apoptosis-associated speck-like protein containing a CARD (ASC) and bruton's tyrosine kinase (BTK). In platelets, however, the regulatory triggers and the functional effects of the NLRP3 inflammasome are unknown. Here, we show in vitro that the platelet NLRP3 inflammasome contributes to platelet activation, aggregation, and thrombus formation. NLRP3 activity, as monitored by caspase-1 activation and cleavage and secretion of IL-1β, was upregulated in activated platelets, which was dependent on platelet BTK. Pharmacological inhibition or genetic ablation of BTK in platelets led to decreased platelet activation, aggregation, and in vitro thrombus formation. We identify a functionally relevant link between BTK and NLRP3 in platelets, with potential implications in disease states associated with abnormal coagulation and inflammation., (Copyright © 2016 Elsevier Inc. All rights reserved.)
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- 2017
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40. Outcomes of interventions for carotid blowout syndrome in patients with head and neck cancer.
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Liang NL, Guedes BD, Duvvuri U, Singh MJ, Chaer RA, Makaroun MS, and Sachdev U
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- Adult, Aged, Carcinoma, Squamous Cell diagnosis, Carcinoma, Squamous Cell mortality, Carcinoma, Squamous Cell therapy, Carotid Artery Diseases diagnostic imaging, Carotid Artery Diseases etiology, Carotid Artery Diseases mortality, Disease-Free Survival, Female, Head and Neck Neoplasms diagnosis, Head and Neck Neoplasms mortality, Head and Neck Neoplasms therapy, Hemorrhage diagnosis, Hemorrhage etiology, Hemorrhage mortality, Hospital Mortality, Humans, Kaplan-Meier Estimate, Ligation, Male, Medical Records, Middle Aged, Neoplasm Staging, Postoperative Hemorrhage etiology, Proportional Hazards Models, Recurrence, Retrospective Studies, Risk Factors, Rupture, Spontaneous, Squamous Cell Carcinoma of Head and Neck, Stroke etiology, Syndrome, Tertiary Care Centers, Time Factors, Treatment Outcome, Blood Vessel Prosthesis Implantation adverse effects, Blood Vessel Prosthesis Implantation mortality, Carcinoma, Squamous Cell complications, Carotid Artery Diseases therapy, Embolization, Therapeutic adverse effects, Embolization, Therapeutic mortality, Endovascular Procedures adverse effects, Endovascular Procedures mortality, Head and Neck Neoplasms complications, Hemorrhage therapy
- Abstract
Background: The purpose of this study was to examine outcomes of a patient cohort undergoing intervention for carotid blowout syndrome associated with head and neck cancer., Methods: Patients with head and neck cancer who presented with carotid distribution bleeding from 2000 to 2014 were identified in the medical record. Primary outcomes were short- and midterm mortality and recurrent bleeding. Standard statistical methods and survival analysis were used to analyze study population characteristics and outcomes., Results: Thirty-seven patients were included in the study. The mean age was 60.1 ± 11.4 years (74% male). All malignancies were squamous cell type, stage IV, in a variety of primary locations: 32% oral cavity, 24% larynx, 16% superficial neck, with the remainder in the oropharynx, nasopharynx, and hypopharynx. Fifty-one percent of bleeds were of common carotid, 29% external carotid, and 19% internal carotid origin. Among the patients, 68% presented with acute hemorrhage, 24% with impending bleed, and 8% with threatened bleed. All patients underwent intervention: 38% received endovascular coil embolization, 30% stent grafts, 22% surgical ligation, and 10% primary vessel repair or bypass grafting. Although major complications were rare, 10.8% of patients had perioperative stroke. Sixteen recurrent bleeding episodes involving 12 arteries occurred in 11 patients (29.73%). Median rebleeding time was 7 days (interquartile range, 6-49). Estimated recurrent bleeding risk at 30 days and 6 months was 24% and 34%, respectively. Of the patients, 91.9% survived to hospital discharge. The 90-day and 1-year estimated survivals were 60.9% and 36.6%, respectively., Conclusions: Carotid blowout syndrome associated with head and neck cancer carries poor mid- and long-term prognoses; however, mortality may be related more to the advanced stage of disease rather than carotid involvement or associated intervention. Both surgical and endovascular approaches may be efficacious in cases of acute hemorrhage but carry a significant risk of periprocedural stroke and recurrent bleeding., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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41. Reply.
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Avgerinos ED, Sachdev U, Chaer RA, Leers SA, and Makaroun MS
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- Female, Humans, Male, Blood Vessel Prosthesis, Ischemia surgery, Leg blood supply, Veins transplantation
- Published
- 2016
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42. The Toll of Vascular Insufficiency: Implications for the Management of Peripheral Arterial Disease.
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Xu J and Sachdev U
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- Adaptor Proteins, Vesicular Transport genetics, Adaptor Proteins, Vesicular Transport immunology, Arteries pathology, Gene Expression Regulation, Humans, Immunity, Innate, Ischemia genetics, Ischemia pathology, Muscular Diseases genetics, Muscular Diseases pathology, Myeloid Differentiation Factor 88 genetics, Myeloid Differentiation Factor 88 immunology, Myocytes, Cardiac immunology, Myocytes, Cardiac pathology, Peripheral Arterial Disease genetics, Peripheral Arterial Disease pathology, Signal Transduction, Toll-Like Receptors genetics, Arteries immunology, Ischemia immunology, Muscular Diseases immunology, Peripheral Arterial Disease immunology, Toll-Like Receptors immunology
- Abstract
Peripheral artery disease (PAD) can result in limb loss within six months of diagnosis in a subset of patients who cannot undergo endovascular or surgical revascularization yet continues to maintain a marginal position in cardiovascular research. While a body of literature continues to grow describing the role of danger signaling and innate immunity in cardiac biology, the role of these pathways in the ischemic myopathy associated with PAD has not been extensively studied. The following report will review the current literature on the role of Toll-like receptor (TLR) signaling in cardiovascular biology as well as in nonischemic myopathy. While attenuation of TLR signaling has not been shown to be clinically useful in the treatment of infectious inflammation, it may show promise in the management of severe arterial insufficiency.
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- 2016
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43. P2Y2 nucleotide receptor mediates arteriogenesis in a murine model of hind limb ischemia.
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McEnaney RM, Shukla A, Madigan MC, Sachdev U, and Tzeng E
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- Animals, Arteries physiopathology, Blood Flow Velocity, Collateral Circulation, Disease Models, Animal, Hindlimb, Ischemia genetics, Ischemia pathology, Ischemia physiopathology, Laser-Doppler Flowmetry, Macrophages metabolism, Mice, Inbred C57BL, Mice, Knockout, Muscle, Skeletal pathology, Necrosis, Perfusion Imaging methods, Receptors, Purinergic P2Y2 deficiency, Receptors, Purinergic P2Y2 genetics, Regional Blood Flow, Signal Transduction, Time Factors, Arteries metabolism, Ischemia metabolism, Muscle, Skeletal blood supply, Neovascularization, Physiologic, Receptors, Purinergic P2Y2 metabolism
- Abstract
Objective: Arteriogenesis represents the maturation of preformed vascular connections in response to flow changes and shear stress. These collateral vessels can restore up to 60% of the native blood flow. Shear stress and vascular injury can induce the release of nucleotides from vascular smooth muscle cells and platelets that can serve as signaling ligands, suggesting they may be involved in mediating arteriogenesis. The P2Y2 nucleotide receptor (P2Y2R) has also been shown to mediate smooth muscle migration and arterial remodeling. Thus, we hypothesize that P2Y2R mediates arteriogenesis in response to ischemia., Methods: Hind limb ischemia was induced by femoral artery ligation (FAL) in C57Bl/6NJ or P2Y2R negative mice (P2Y2(-/-)). Hind limb perfusion was measured with laser Doppler perfusion imaging and compared with the sham-operated contralateral limb immediately and at 3, 7, 14, 21, and 28 days after ligation. Collateral vessel size was measured by Microfil casting. Muscle specimens were harvested and analyzed with immunohistochemistry for Ki67, vascular cell adhesion molecule, macrophages, and muscle viability by hematoxylin and essoin stain., Results: Hind limb ischemia induced by FAL in C57Bl/6NJ mice resulted in significant ischemia as measured by laser Doppler perfusion imaging. There was rapid recovery to nearly normal levels of perfusion by 2 weeks. FAL in P2Y2(-/-) mice resulted in severe ischemia with greater tissue loss. Recovery of perfusion was impaired, achieving only 40% compared with wild-type mice by 28 days. Collateral vessels in the P2Y2(-/-) mice were underdeveloped, with reduced vascular cell proliferation and smaller vessel size. The collaterals were ∼65% the size of wild-type collateral vessels (P = .011). Angiogenesis at 28 days in the ischemic muscle, however, was greater in the P2Y2(-/-) mice (P < .001), possibly related to persistent ischemia leading and angiogenic drive. Early macrophage recruitment was reduced by nearly 70% in P2Y2(-/-) despite significantly more myocyte necrosis. However, inflammation was greater at 28 days in the P2Y2(-/-) mice., Conclusions: P2Y2R deficiency does not alter baseline collateral vessel formation but does significantly impair collateral maturation, with resultant persistent limb ischemia despite enhanced angiogenesis. These findings reinforce the importance of arteriogenesis in the recovery of perfusion in ischemic tissues compared with angiogenesis. They also support the role of P2Y2R in mediating this process. The mechanism by which P2Y2R mediates arteriogenesis may involve the recruitment of inflammatory cells to the ischemic tissues, which is essential to arteriogenesis. Approaches to target P2Y2R may yield new therapeutic strategies for the treatment of arterial occlusive disease., (Published by Elsevier Inc.)
- Published
- 2016
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44. Autologous alternative veins may not provide better outcomes than prosthetic conduits for below-knee bypass when great saphenous vein is unavailable.
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Avgerinos ED, Sachdev U, Naddaf A, Doucet DR, Mohapatra A, Leers SA, Chaer RA, and Makaroun MS
- Subjects
- Aged, Aged, 80 and over, Blood Vessel Prosthesis Implantation, Female, Humans, Limb Salvage, Male, Middle Aged, Saphenous Vein transplantation, Transplantation, Autologous, Vascular Patency, Blood Vessel Prosthesis, Ischemia surgery, Leg blood supply, Veins transplantation
- Abstract
Background: There is a need to better define the role of alternative autologous vein (AAV) segments over contemporary prosthetic conduits in patients with critical limb ischemia when great saphenous vein (GSV) is not available for use as the bypass conduit., Methods: Consecutive patients who underwent bypass to infrageniculate targets between 2007 and 2011 were categorized in three groups: GSV, AAV, and prosthetic. The primary outcome was graft patency. The secondary outcome was limb salvage. Cox proportional hazards regression was used to adjust for baseline confounding variables., Results: A total of 407 infrainguinal bypasses to below-knee targets were analyzed; 255 patients (63%) received a single-segment GSV, 106 patients (26%) received an AAV, and 46 patients (11%) received a prosthetic conduit. Baseline characteristics were similar among groups, with the exception of popliteal targets and anticoagulation use being more frequent in the prosthetic group. Primary patency at 2 and 5 years was estimated at 47% and 32%, respectively, for the GSV group; 24% and 23% for the AAV group; and 43% and 38% for the prosthetic group. Primary assisted patency at 2 and 5 years was estimated at 71% and 55%, respectively, for the GSV group; 53% and 51% for the AAV group; and 45% and 40% for the prosthetic group. Secondary patency at 2 and 5 years was estimated at 75% and 60%, respectively, for the GSV group; 57% and 55% for the AAV group; and 46% and 41% for the prosthetic group. In Cox analysis, primary patency (hazard ratio [HR], 0.55; P < .001; 95% confidence interval [CI], 0.404-0.758), primary assisted patency (HR, 0.57; P = .004; 95% CI, 0.388-0.831), and secondary patency (HR, 0.56; P = .005; 95% CI, 0.372-0.840) were predicted by GSV compared with AAV, but there was no difference between AAV and prosthetic grafts except for the primary patency, for which prosthetic was protective (HR, 0.38; P < .001; 95% CI, 0.224-0.629). Limb salvage was similar among groups., Conclusions: AAV conduits may not offer a significant patency advantage in midterm follow-up over prosthetic bypasses., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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45. TLR4 Deters Perfusion Recovery and Upregulates Toll-like Receptor 2 (TLR2) in Ischemic Skeletal Muscle and Endothelial Cells.
- Author
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Xu J, Benabou K, Cui X, Madia M, Tzeng E, Billiar T, Watkins S, and Sachdev U
- Subjects
- Animals, Endothelial Cells metabolism, Endothelial Cells pathology, Femoral Artery growth & development, Femoral Artery pathology, Femoral Artery surgery, Gene Expression Regulation, HMGB1 Protein biosynthesis, Hindlimb growth & development, Hindlimb metabolism, Hindlimb pathology, Humans, Inflammation pathology, Interleukin-6 biosynthesis, Ischemia metabolism, Ischemia pathology, Male, Mice, Mice, Knockout, Muscle, Skeletal metabolism, Muscle, Skeletal pathology, Signal Transduction, Toll-Like Receptor 2 biosynthesis, Toll-Like Receptor 4 biosynthesis, Inflammation genetics, Ischemia genetics, Neovascularization, Physiologic genetics, Toll-Like Receptor 2 genetics, Toll-Like Receptor 4 genetics
- Abstract
Toll-like receptors (TLRs) play an important role in regulating muscle regeneration and angiogenesis in response to ischemia. TLR2 knockout mice exhibit pronounced skeletal muscle necrosis and abnormal vessel architecture after femoral artery ligation, suggesting that TLR2 signaling is protective during ischemia. TLR4, an important receptor in inflammatory signaling, has been shown to regulate TLR2 expression in other systems. We hypothesize that a similar relationship between TLR4 and TLR2 may exist in hindlimb ischemia in which TLR4 upregulates TLR2, a mediator of angiogenesis and perfusion recovery. We examined the expression of TLR2 in unstimulated and in TLR-agonist treated endothelial cells (ECs). TLR2 expression (low in control ECs) was upregulated by lipopolysaccharide, the danger signal high mobility group box-1, and hypoxia in a TLR4-dependent manner. Endothelial tube formation on Matrigel as well as EC permeability was assessed as in vitro measures of angiogenesis. Time-lapse imaging demonstrated that ECs lacking TLR4 formed more tubes, whereas TLR2 knockdown ECs exhibited attenuated tube formation. TLR2 also mediated EC permeability, an initial step during angiogenesis, in response to high-mobility group box-1 (HMGB1) that is released by cells during hypoxic injury. In vivo, ischemia-induced upregulation of TLR2 required intact TLR4 signaling that mediated systemic inflammation, as measured by local and systemic IL-6 levels. Similar to our in vitro findings, vascular density and limb perfusion were both enhanced in the absence of TLR4 signaling, but not if TLR2 was deleted. These findings indicate that TLR2, in the absence of TLR4, improves angiogenesis and perfusion recovery in response to ischemia.
- Published
- 2015
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46. MyD88 and TRIF mediate divergent inflammatory and regenerative responses to skeletal muscle ischemia.
- Author
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Sachdev U, Cui X, Xu J, Xu J, and Tzeng E
- Abstract
We have previously shown that MyD88 KO mice appear protected from ischemic muscle injury while TRIF KO mice exhibit sustained necrosis after femoral artery ligation (FAL). However, our previous data did not differentiate whether the protective effect of absent MyD88 signaling was secondary to attenuated injury after FAL or quicker recovery from the insult. The purpose of this study was to delineate these different possibilities. On the basis of previous findings, we hypothesized that MyD88 signaling promotes enhanced inflammation while TRIF mediates regeneration after skeletal muscle ischemia. Our results show that after FAL, both MyD88 KO mice and TRIF KO mice have evidence of ischemia, as do their control counterparts. However, MyD88 KO mice had lower levels of serum IL-6 24 h after FAL, while TRIF KO mice demonstrated sustained serum IL-6 up to 1 week after injury. Additionally, MyD88 KO mice had higher nuclear content and larger myofibers than control animals 1 week after injury. IL-6 is known to have differential effects in myoblast function, and can inhibit proliferation and differentiation. In tibialis anterior muscle harvested from injured animals, IL-6 levels were higher and the proliferative marker MyoD was lower in TRIF KO mice by PCR. Furthermore, expression of MyD88 appeared to be higher in skeletal muscle of TRIF KO mice. In vitro, we showed that myoblast differentiation and proliferation were attenuated in response to IL-6 treatment giving credence to the finding that low IL-6 in MyD88 KO mice may be responsible for larger myocyte sizes 1 week after FAL. We conclude that MyD88 and TRIF work in concert to mediate a balanced response to ischemic injury., (© 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)
- Published
- 2014
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47. HMGB1 and TLR4 mediate skeletal muscle recovery in a murine model of hindlimb ischemia.
- Author
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Sachdev U, Cui X, and Tzeng E
- Subjects
- Animals, Antibodies, Neutralizing administration & dosage, Cells, Cultured, Disease Models, Animal, Endothelial Cells metabolism, Extracellular Signal-Regulated MAP Kinases metabolism, Femoral Artery surgery, HMGB1 Protein immunology, Hindlimb, Humans, Ischemia genetics, Ischemia pathology, Ischemia physiopathology, Laser-Doppler Flowmetry, Ligation, Male, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Knockout, Muscle, Skeletal pathology, Necrosis, Perfusion Imaging methods, Phosphorylation, Receptor for Advanced Glycation End Products, Receptors, Immunologic genetics, Receptors, Immunologic metabolism, Regeneration, Regional Blood Flow, Signal Transduction, Time Factors, Toll-Like Receptor 4 deficiency, Toll-Like Receptor 4 genetics, HMGB1 Protein metabolism, Ischemia metabolism, Muscle, Skeletal blood supply, Muscle, Skeletal metabolism, Neovascularization, Physiologic, Toll-Like Receptor 4 metabolism
- Abstract
Background: We have previously shown that the danger signal high-mobility group box 1 (HMGB1) promotes angiogenesis when administered to ischemic muscle. HMGB1 signals through Toll-like receptor 4 (TLR4) as well as the receptor for advanced glycation end-products (RAGE). However, the actions of these receptors in ischemic injury and muscle recovery are not known. We hypothesize that TLR4 mediates tissue recovery and angiogenesis in response to ischemia., Methods: Femoral artery ligation was performed in control, TLR4 competent (C3H/HeOuJ) and incompetent (C3H/HeJ) mice, as well as RAGE knockout mice and their C57B6 control counterparts. In other experiments, control mice were pretreated with anti-HMGB1 neutralizing antibody before femoral artery ligation. After 2 weeks, limb perfusion was evaluated using laser Doppler perfusion imaging and reported as the ratio of blood flow in the ischemic to nonischemic limb. Muscle necrosis, fat replacement, and vascular density in the anterior tibialis muscle were quantified histologically. In vitro, TLR4 and RAGE expression was evaluated in human dermal microvascular endothelial cells in response to hypoxia. Human dermal microvascular endothelial cells treated with HMGB1 alone and in the presence of anti-TLR4 antibody were probed for phosphorylated extracellular signal-regulated kinase (ERK), a signaling molecule critical to endothelial cell (EC) angiogenic behavior., Results: Both anti-HMGB1 antibody as well as defective TLR4 signaling in HeJ mice resulted in prominent muscle necrosis 2 weeks after femoral artery ligation. Control HeOuJ mice had less necrosis than TLR4 incompetent HeJ mice, but a greater amount of fat replacement. In contrast to control C3H mice, control C57B6 mice demonstrated prominent muscle regeneration with very little necrosis. Muscle regeneration was not dependent on RAGE. While vascular density did not differ between strains, mice with intact RAGE and TLR4 signaling had less blood flow in ischemic limbs compared with mutant strains. In vitro, EC TLR4 expression increased in response to hypoxia while TLR4 antagonism decreased HMGB1-induced activation of extracellular signal-regulated kinase., Conclusions: Both HMGB1 and TLR4 protect against muscle necrosis after hindlimb ischemia. However, muscle regeneration does not appear to be tied to vascular density. HMGB1 likely activates angiogenic behavior in ECs in vitro, and this activation may be modulated by TLR4. The improvement in blood flow seen in mice with absent TLR4 and RAGE signaling may suggest anti-angiogenic roles for both receptors, or vasoconstriction induced by TLR4 and RAGE mediated inflammatory pathways., (Published by Mosby, Inc.)
- Published
- 2013
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48. High mobility group box 1 promotes endothelial cell angiogenic behavior in vitro and improves muscle perfusion in vivo in response to ischemic injury.
- Author
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Sachdev U, Cui X, Hong G, Namkoong S, Karlsson JM, Baty CJ, and Tzeng E
- Subjects
- Angiogenesis Inducing Agents administration & dosage, Angiogenesis Inhibitors pharmacology, Animals, Antibodies pharmacology, Autophagy, Blotting, Western, Cell Hypoxia, Disease Models, Animal, Endothelial Cells drug effects, Endothelial Cells immunology, Endothelial Cells pathology, HMGB1 Protein administration & dosage, HMGB1 Protein antagonists & inhibitors, Hindlimb, Humans, Immunity, Innate, Injections, Intramuscular, Ischemia drug therapy, Ischemia immunology, Ischemia pathology, Ischemia physiopathology, Laser-Doppler Flowmetry, Male, Mice, Mice, Inbred C3H, Microtubule-Associated Proteins metabolism, Muscle Fibers, Skeletal drug effects, Muscle Fibers, Skeletal immunology, Muscle Fibers, Skeletal pathology, Muscle, Skeletal drug effects, Muscle, Skeletal immunology, Muscle, Skeletal pathology, Oxygen metabolism, Protein Transport, Regional Blood Flow, Time Factors, Endothelial Cells metabolism, HMGB1 Protein metabolism, Ischemia metabolism, Muscle Fibers, Skeletal metabolism, Muscle, Skeletal blood supply, Muscle, Skeletal metabolism, Neovascularization, Physiologic drug effects
- Abstract
Objectives: The angiogenic drive in skeletal muscle ischemia remains poorly understood. Innate inflammatory pathways are activated during tissue injury and repair, suggesting that this highly conserved pathway may be involved in ischemia-induced angiogenesis. We hypothesize that one of the endogenous ligands for innate immune signaling, high mobility group box 1 (HMGB1), in combination with autophagic responses to hypoxia or nutrient deprivation, plays an important role in angiogenesis., Methods: Human dermal microvascular endothelial cells (ECs) were cultured in normoxia or hypoxia (1% oxygen). Immunocytochemical analysis of HMGB1 subcellular localization, evaluation of tube formation, and Western blot analysis of myotubule light-chain 3I (LC3I) conversion to LC3II, as a marker of autophagy, were conducted. 3-Methyladenine (3MA), chloroquine, or rapamycin were administered to inhibit or promote autophagy, respectively. In vivo, a murine hind limb ischemia model was performed. Muscle samples were collected at 4 hours to evaluate for nuclear HMGB1 and at 14 days to examine endothelial density. Perfusion recovery in the hind limbs was calculated by laser Doppler perfusion imaging (LDPI)., Results: Hypoxic ECs exhibited reduced nuclear HMGB1 staining compared with normoxic cells (mean fluorescence intensity, 186.9 ± 17.1 vs 236.0 ± 1.6, P = .01) with a concomitant increase in cytosolic staining. HMGB1 treatment of ECs enhanced tube formation, an angiogenic phenotype of ECs. Neutralization of endogenous HMGB1 markedly impaired tube formation and inhibited LC3II formation. Inhibition of autophagy with 3MA or chloroquine abrogated tube formation, whereas its induction with rapamycin enhanced tubing and promoted HMGB1 translocation. In vivo, ischemic skeletal muscle showed reduced numbers of HMGB1-positive myocyte nuclei compared with nonischemic muscle (34.9% ± 1.9% vs 51.7% ± 2.0%, P < .001). Injection of HMGB1 into ischemic hind limbs increased perfusion recovery by 21% and increased EC density (49.2 ± 4.1 vs 34.2 ± 3.4 ECs/high-powered field, respectively; P = .02) at 14 days compared with control hind limbs., Conclusions: Nuclear release of HMGB1 and autophagy occur in ECs in response to hypoxia or serum depletion. HMGB1 and autophagy are necessary and likely play an interdependent role in promoting the angiogenic behavior of ECs. In vivo, HMGB1 promotes perfusion recovery and increased EC density after ischemic injury. These findings suggest a possible mechanistic link between autophagy and HMGB1 in EC angiogenic behavior and support the importance of innate immune pathways in angiogenesis., (Published by Mosby, Inc.)
- Published
- 2012
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49. TLR2 and TLR4 mediate differential responses to limb ischemia through MyD88-dependent and independent pathways.
- Author
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Sachdev U, Cui X, McEnaney R, Wang T, Benabou K, and Tzeng E
- Subjects
- Animals, Cells, Cultured, Hindlimb metabolism, Hindlimb pathology, Humans, Ischemia genetics, Male, Mice, Mice, Knockout, Muscle, Skeletal metabolism, Muscle, Skeletal pathology, Myeloid Differentiation Factor 88 genetics, Necrosis metabolism, Necrosis pathology, Neovascularization, Pathologic metabolism, Neovascularization, Pathologic pathology, Signal Transduction genetics, Signal Transduction physiology, Toll-Like Receptor 2 genetics, Toll-Like Receptor 4 genetics, Ischemia metabolism, Myeloid Differentiation Factor 88 metabolism, Toll-Like Receptor 2 metabolism, Toll-Like Receptor 4 metabolism
- Abstract
Introduction: The danger signal HMGB1 is released from ischemic myocytes, and mediates angiogenesis in the setting of hindlimb ischemia. HMGB1 is a ligand for innate immune receptors TLR2 and TLR4. While both TLR2 and TLR4 signal through myeloid differentiation factor 88 (MyD88), TLR4 also uniquely signals through TIR-domain-containing adapter-inducing interferon-β (TRIF). We hypothesize that TLR2 and TLR4 mediate ischemic myocyte regeneration and angiogenesis in a manner that is dependent on MyD88 signaling., Methods: Mice deficient in TLR2, TLR4, MyD88 and TRIF underwent femoral artery ligation in the right hindlimb. Laser Doppler perfusion imaging was used to assess the initial degree of ischemia and the extent of perfusion recovery. Muscle regeneration, necrosis and fat replacement at 2 weeks post-ligation were assessed histologically and vascular density was quantified by immunostaining. In vitro, endothelial tube formation was evaluated in matrigel in the setting of TLR2 and TLR4 antagonism., Results: While control and TLR4 KO mice demonstrated prominent muscle regeneration, both TLR2 KO and TRIF KO mice exhibited marked necrosis with significant inflammatory cell infiltrate. However, MyD88 KO mice had a minimal response to the ischemic insult with little evidence of injury. This observation could not be explained by differences in perfusion recovery which was similar at two weeks in all the strains of mice. TLR2 KO mice demonstrated abnormal vessel morphology compared to other strains and impaired tube formation in vitro., Discussion: TLR2 and TRIF signaling are necessary for muscle regeneration after ischemia while MyD88 may instead mediate muscle injury. The absence of TLR4 did not affect muscle responses to ischemia. TLR4 may mediate inflammatory responses through MyD88 that are exaggerated in the absence of TLR2. Additionally, the actions of TLR4 through TRIF may promote regenerative responses that are required for recovery from muscle ischemia.
- Published
- 2012
- Full Text
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50. Endovascular stent-graft repair of failed endovascular abdominal aortic aneurysm repair.
- Author
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Baril DT, Silverberg D, Ellozy SH, Carroccio A, Jacobs TS, Sachdev U, Teodorescu VJ, Lookstein RA, and Marin ML
- Subjects
- Aged, Aortic Aneurysm, Abdominal mortality, Blood Vessel Prosthesis Implantation adverse effects, Equipment Design, Female, Follow-Up Studies, Humans, Male, Reoperation, Retrospective Studies, Time Factors, Treatment Failure, Treatment Outcome, Aortic Aneurysm, Abdominal surgery, Blood Vessel Prosthesis, Blood Vessel Prosthesis Implantation instrumentation, Stents, Vascular Surgical Procedures
- Abstract
Despite high initial technical success, the long-term durability of endovascular abdominal aortic aneurysm repair (EVAR) continues to be a concern. Following EVAR, patients can experience endoleaks, device migration, device fractures, or aneurysm growth that may require intervention. The purpose of this study was to review all patients treated with secondary endovascular devices at our institution for failed EVAR procedures. Over an 8-year period, 988 patients underwent EVAR, of whom 42 (4.3%) required secondary interventions involving placement of additional endovascular devices. Data regarding patient characteristics, aneurysm size, initial device type, time until failure, failure etiology, secondary interventions, and outcomes were reviewed. The mean time from initial operation until second operation was 34.1 months. Failures included type I endoleaks in 38 patients (90.5%), type III endoleaks in two patients (4.8%), and enlarging aneurysms without definite endoleaks in two patients (4.8%). The overall technical success rate for secondary repair was 92.9% (39/42). Perioperative complications occurred in nine patients (21.4%), including wound complications (n = 6), cerebrovascular accident (CVA) (n = 1), foot drop (n = 1), and death (n = 1). Mean follow-up following secondary repair was 16.4 months (range 1-50). Eighty-six percent of patients treated with aortouni-iliac devices had successful repairs compared to 45% of patients treated with proximal cuffs. Ten patients (23.8%) had persistent or recurrent type I or type III endoleaks following revision. Of these, four had tertiary interventions, including two patients who had additional devices placed. Failures following EVAR occur in a small but significant number of patients. When anatomically possible, endovascular revision offers a safe means of treating these failures. Aortouni-iliac devices appear to offer a more durable repair than the proximal cuff for treatment of proximal type I endoleaks. Midterm results indicate that these patients may require additional procedures but have a low rate of aneurysm-related mortality. Longer-term follow-up is necessary to determine the durability of these endovascular revisions.
- Published
- 2008
- Full Text
- View/download PDF
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