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Novel mitochondrial mechanisms of cognitive regulation in subjects with cognitive impairments
- B. Bigio, R. Lima-Filho, O. Barnhill, F. Sudo, C. Drummond, N. Assunção, B. Vanderborght, F. Tovar-Moll, P. Mattos, S. Ferreira, F. De Felice, M. Lourenco, C. Nasca
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S611
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Introduction
Prior mechanistic studies in rodents showed decreased levels of the pivotal mitochondrial metabolite acetyl-L-carnitine (LAC) in relation to cognitive deficits and depressive-like behavior (Neuron 2017, 10.1016/j.neuron.2017.09.020, PNAS 2013, 10.1073/pnas.1216100110), providing the basis for the current translational study.
ObjectivesThe main objective of this work was to ascertain the role of this specific mitochondrial signaling pathway in subjects with cognitive impairments (CI), and potential sex differences in these mechanisms.
MethodsWe used computational approaches, ultraperformance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) and available plasma samples from a well-characterized cohort of 71 subjects, including subjects with CI and age- and sex-matched cognitively healthy controls (HC).
ResultsOur newest findings showed decreased levels of LAC in subjects with CI as compared to age- and sex-matched HC. We also found important sex differences in carnitine levels in relation to cognitive function as assessed by using the Mini Mental Status Exam (MMSE). Specifically, the degree of carnitine deficiency reflected the severity of cognitive dysfunction in a sex-specific manner. Using computational approaches, we found that the integration of these mitochondrial measures with canonical biomarkers improves diagnostic accuracy.
ConclusionsThe current findings of sex differences in carnitine deficiency in subjects with CI suggest a possible sex-specific mitochondrial phenotype of vulnerability to cognitive dysfunction, and point to LAC-related mitochondrial metabolism as a new signaling pathway of cognitive regulation.
Disclosure of InterestNone Declared
Probability of major depression diagnostic classification using semi-structured versus fully structured diagnostic interviews
- Brooke Levis, Andrea Benedetti, Kira E. Riehm, Nazanin Saadat, Alexander W. Levis, Marleine Azar, Danielle B. Rice, Matthew J. Chiovitti, Tatiana A. Sanchez, Pim Cuijpers, Simon Gilbody, John P. A. Ioannidis, Lorie A. Kloda, Dean McMillan, Scott B. Patten, Ian Shrier, Russell J. Steele, Roy C. Ziegelstein, Dickens H. Akena, Bruce Arroll, Liat Ayalon, Hamid R. Baradaran, Murray Baron, Anna Beraldi, Charles H. Bombardier, Peter Butterworth, Gregory Carter, Marcos H. Chagas, Juliana C. N. Chan, Rushina Cholera, Neerja Chowdhary, Kerrie Clover, Yeates Conwell, Janneke M. de Man-van Ginkel, Jaime Delgadillo, Jesse R. Fann, Felix H. Fischer, Benjamin Fischler, Daniel Fung, Bizu Gelaye, Felicity Goodyear-Smith, Catherine G. Greeno, Brian J. Hall, John Hambridge, Patricia A. Harrison, Ulrich Hegerl, Leanne Hides, Stevan E. Hobfoll, Marie Hudson, Thomas Hyphantis, Masatoshi Inagaki, Khalida Ismail, Nathalie Jetté, Mohammad E. Khamseh, Kim M. Kiely, Femke Lamers, Shen-Ing Liu, Manote Lotrakul, Sonia R. Loureiro, Bernd Löwe, Laura Marsh, Anthony McGuire, Sherina Mohd Sidik, Tiago N. Munhoz, Kumiko Muramatsu, Flávia L. Osório, Vikram Patel, Brian W. Pence, Philippe Persoons, Angelo Picardi, Alasdair G. Rooney, Iná S. Santos, Juwita Shaaban, Abbey Sidebottom, Adam Simning, Lesley Stafford, Sharon Sung, Pei Lin Lynnette Tan, Alyna Turner, Christina M. van der Feltz-Cornelis, Henk C. van Weert, Paul A. Vöhringer, Jennifer White, Mary A. Whooley, Kirsty Winkley, Mitsuhiko Yamada, Yuying Zhang, Brett D. Thombs
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- Journal:
- The British Journal of Psychiatry / Volume 212 / Issue 6 / June 2018
- Published online by Cambridge University Press:
- 02 May 2018, pp. 377-385
- Print publication:
- June 2018
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Background
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
AimsTo evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
MethodData collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
ResultsA total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
ConclusionsThe MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interestDrs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Contributors
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- By Linda S. Aglio, Cyrus Ahmadi Yazdi, Syed Irfan Qasim Ali, Caryn Barnet, Jessica Bauerle, Felicity Billings, Evan Blaney, Beverly Chang, Christopher Chen, Zinaida Chepurny, Hyung Sun Choi, Allison Clark, Lauren J. Cornella, Lisa Crossley, Michael D’Ambra, Galina Davidyuk, Whitney de Luna, Manisha S. Desai, Sukumar P. Desai, Kelly G. Elterman, Michaela K. Farber, Iuliu Fat, Jaida Fitzgerald, Devon Flaherty, John A. Fox, Gyorgy Frendl, Rejean Gareau, Joseph M. Garfield, Andrea Girnius, Laverne D. Gugino, J. Tasker Gundy, Carly C. Guthrie, Lisa M. Hammond, M. Tariq Hanifi, James Hardy, Philip M. Hartigan, Thomas Hickey, Richard Hsu, Mohab Ibrahim, David Janfaza, Yuka Kiyota, Suzanne Klainer, Benjamin Kloesel, Hanjo Ko, Bhavani Kodali, Vesela Kovacheva, J. Matthew Kynes, Robert W. Lekowski, Joyce Lo, Jeffrey Lu, Alvaro A. Macias, Zahra M. Malik, Erich N. Marks, Brendan McGinn, Jonathan R. Meserve, Annette Mizuguchi, Srdjan S. Nedeljkovic, Ju-Mei Ng, Michael Nguyen, Olutoyin Okanlawon, Jennifer Oliver, Krishna Parekh, Jessica Patterson, Christian Peccora, Pete Pelletier, Sujatha Pentakota, James H. Philip, Marc Philip T. Pimentel, Timothy D. Quinn, Elizabeth M. Rickerson, Susan L. Sager, Julia Serber, Shaheen Shaikh, Stanton Shernan, David Silver, Alissa Sodickson, Pingping Song, George P. Topulos, Agnieszka Trzcinka, Richard D. Urman, Rosemary Uzomba, Joshua Vacanti, Assia Valovska, Michael Vaninetti, Scott W. Vaughan, Kamen Vlassakov, Christopher Voscopoulos, Emily L. Wang, Laura Westfall, Zhiling Xiong, Stephanie Yacoubian, Dongdong Yao, Martin Zammert, Maksim Zayaruzny, Jose Luis Zeballos, Natthasorn Zinboonyahgoon, Jie Zhou
- Edited by Linda S. Aglio, Robert W. Lekowski, Richard D. Urman
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- Book:
- Essential Clinical Anesthesia Review
- Published online:
- 05 February 2015
- Print publication:
- 08 January 2015, pp xi-xvi
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Ionising radiation metrology for the metallurgical industry
- E. García-Toraño, F. Tzika, O. Burda, V. Peyrés, M. Mejuto, T. Crespo, U. Wätjen, D. Arnold, V. Sochor, A. Svec, P. Carconi, P. de Felice, J. Tecl
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- Journal:
- International Journal of Metrology and Quality Engineering / Volume 5 / Issue 3 / 2014
- Published online by Cambridge University Press:
- 03 November 2014, 301
- Print publication:
- 2014
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Every year millions tons of steel are produced worldwide from recycled scrap loads. Although the detection systems in the steelworks prevent most orphan radioactive sources from entering the furnace, there is still the possibility of accidentally melting a radioactive source. The MetroMetal project, carried out in the frame of the European Metrology Research Programme (EMRP), addresses this problem by studying the existing measurement systems, developing sets of reference sources in various matrices (cast steel, slag, fume dust) and proposing new detection instruments. This paper presents the key lines of the project and describes the preparation of radioactive sources as well as the intercomparison exercises used to test the calibration and correction methods proposed within the project.
Contributors
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- By Victoria M. Allen, Frederic Amant, Sarah Armstrong, Thomas F. Baskett, Michael A. Belfort, Meredith Birsner, Renee D. Boss, Leanne Bricker, Josaphat K. Byamugisha, Giorgio Capogna, Michael P. Casaer, Frank A. Chervenak, Vicki Clark, Filip Claus, Malachy O. Columb, Charles Cox, Jean T. Cox, Vegard Dahl, John Davison, Jan Deprest, Clifford S. Deutschman, Roland Devlieger, Karim Djekidel, Steven Dymarkowski, Roshan Fernando, Clare Fitzpatrick, Sreedhar Gaddipati, Thierry Girard, Emily Gordon, Ian A. Greer, David Grooms, Sina Haeri, Katy Harrison, Edward J. Hayes, Michelle Hladunewich, Andra H. James, Tracey Johnston, Bellal Joseph, Erin Keely, Ruth Landau, Stephen E. Lapinsky, Susanna I. Lee, Larry Leeman, Hennie Lombaard, Stephen Lu, Alison MacArthur, Laura A. Magee, Paul E. Marik, Laurence B. McCullough, Alexandre Mignon, Carlo Missant, Jack Moodley, Lisa E. Moore, Kate Morse, Warwick D. Ngan Kee, Catherine Nelson-Piercy, Clemens M. Ortner, Geraldine O’Sullivan, Luis D. Pacheco, Fathima Paruk, Melina Pectasides, Nigel Pereira, Patricia Peticca, Sharon T. Phelan, Felicity Plaat, Lauren A. Plante, Michael P. Plevyak, Dianne Plews, Wendy Pollock, Laura C. Price, Peter Rhee, Leiv Arne Rosseland, Kathryn M. Rowan, Helen Ryan, Helen Scholefield, Neil S. Seligman, Nadir Sharawi, Alex Sia, Bob Silver, Mieke Soens, Ulrich J. Spreng, Silvia Stirparo, Nova Szoka, Andrew Tang, Kha M. Tran, Els Troost, Lawrence C. Tsen, Derek Tuffnell, Kristel Van Calsteren, Marc Van de Velde, Marcel Vercauteren, Chris Verslype, Peter von Dadelszen, Carl Waldman, Michelle Walters, Linda Watkins, Paul Westhead, Cynthia A. Wong, Gerda G. Zeeman, Joost J. Zwart
- Edited by Marc van de Velde, Helen Scholefield, Lauren A. Plante
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- Book:
- Maternal Critical Care
- Published online:
- 05 July 2013
- Print publication:
- 04 July 2013, pp ix-xiv
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