A Distinct Metabolite Signature in Military Personnel Exposed to Repetitive Low-Level Blasts
Military Breachers and Range Staff (MBRS) are subjected to repeated sub-concussive blasts, and they often report symptoms that are consistent with a mild traumatic brain injury (mTBI). Biomarkers of blast injury would potentially aid blast injury diagnosis, surveillance and avoidance. Our objective...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Neurology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2022.831792/full |
| _version_ | 1818393748066795520 |
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| author | Michael R. Miller Michael R. Miller Alicia DiBattista Alicia DiBattista Maitray A. Patel Mark Daley Mark Daley Catherine Tenn Ann Nakashima Shawn G. Rhind Shawn G. Rhind Oshin Vartanian Oshin Vartanian Maria Y. Shiu Norleen Caddy Michelle Garrett Doug Saunders Ingrid Smith Rakesh Jetly Rakesh Jetly Rakesh Jetly Douglas D. Fraser Douglas D. Fraser Douglas D. Fraser Douglas D. Fraser Douglas D. Fraser |
| author_facet | Michael R. Miller Michael R. Miller Alicia DiBattista Alicia DiBattista Maitray A. Patel Mark Daley Mark Daley Catherine Tenn Ann Nakashima Shawn G. Rhind Shawn G. Rhind Oshin Vartanian Oshin Vartanian Maria Y. Shiu Norleen Caddy Michelle Garrett Doug Saunders Ingrid Smith Rakesh Jetly Rakesh Jetly Rakesh Jetly Douglas D. Fraser Douglas D. Fraser Douglas D. Fraser Douglas D. Fraser Douglas D. Fraser |
| author_sort | Michael R. Miller |
| collection | DOAJ |
| description | Military Breachers and Range Staff (MBRS) are subjected to repeated sub-concussive blasts, and they often report symptoms that are consistent with a mild traumatic brain injury (mTBI). Biomarkers of blast injury would potentially aid blast injury diagnosis, surveillance and avoidance. Our objective was to identify plasma metabolite biomarkers in military personnel that were exposed to repeated low-level or sub-concussive blast overpressure. A total of 37 military members were enrolled (18 MBRS and 19 controls), with MBRS having participated in 8–20 breaching courses per year, with a maximum exposure of 6 blasts per day. The two cohorts were similar except that the number of blast exposures were significantly higher in the MBRS, and the MBRS cohort suffered significantly more post-concussive symptoms and poorer health on assessment. Metabolomics profiling demonstrated significant differences between groups with 74% MBRS classification accuracy (CA). Feature reduction identified 6 metabolites that resulted in a MBRS CA of 98%, and included acetic acid (23.7%), formate (22.6%), creatine (14.8%), acetone (14.2%), methanol (12,7%), and glutamic acid (12.0%). All 6 metabolites were examined with individual receiver operating characteristic (ROC) curve analyses and demonstrated areas-under-the-curve (AUCs) of 0.82–0.91 (P ≤ 0.001) for MBRS status. Several parsimonious combinations of three metabolites increased accuracy of ROC curve analyses to AUCs of 1.00 (P < 0.001), while a combination of volatile organic compounds (VOCs; acetic acid, acetone and methanol) yielded an AUC of 0.98 (P < 0.001). Candidate biomarkers for chronic blast exposure were identified, and if validated in a larger cohort, may aid surveillance and care of military personnel. Future point-of-care screening could be developed that measures VOCs from breath, with definitive diagnoses confirmed with plasma metabolomics profiling. |
| first_indexed | 2024-12-14T05:50:14Z |
| format | Article |
| id | doaj.art-a3b712022fc149da8e6a41ef4e3cf67e |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-14T05:50:14Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-a3b712022fc149da8e6a41ef4e3cf67e2022-12-21T23:14:44ZengFrontiers Media S.A.Frontiers in Neurology1664-22952022-04-011310.3389/fneur.2022.831792831792A Distinct Metabolite Signature in Military Personnel Exposed to Repetitive Low-Level BlastsMichael R. Miller0Michael R. Miller1Alicia DiBattista2Alicia DiBattista3Maitray A. Patel4Mark Daley5Mark Daley6Catherine Tenn7Ann Nakashima8Shawn G. Rhind9Shawn G. Rhind10Oshin Vartanian11Oshin Vartanian12Maria Y. Shiu13Norleen Caddy14Michelle Garrett15Doug Saunders16Ingrid Smith17Rakesh Jetly18Rakesh Jetly19Rakesh Jetly20Douglas D. Fraser21Douglas D. Fraser22Douglas D. Fraser23Douglas D. Fraser24Douglas D. Fraser25Lawson Health Research Institute, London, ON, CanadaDepartment of Pediatrics, Western University, London, ON, CanadaChildren's Hospital of Eastern Ontario Research Institute, Ottawa, ON, CanadaNeurolytix Inc., Toronto, ON, CanadaDepartment of Computer Science, Western University, London, ON, CanadaDepartment of Computer Science, Western University, London, ON, CanadaThe Vector Institute for Artificial Intelligence, Toronto, ON, CanadaDefence Research and Development Canada, Suffield Research Centre, Medicine Hat, AB, CanadaDefence Research and Development Canada, Toronto Research Centre, Toronto, ON, CanadaDefence Research and Development Canada, Toronto Research Centre, Toronto, ON, CanadaFaculty of Kinesiology & Physical Education, University of Toronto, Toronto, ON, CanadaDefence Research and Development Canada, Toronto Research Centre, Toronto, ON, Canada0Department of Psychology, University of Toronto, Toronto, ON, CanadaDefence Research and Development Canada, Toronto Research Centre, Toronto, ON, CanadaDefence Research and Development Canada, Suffield Research Centre, Medicine Hat, AB, CanadaDefence Research and Development Canada, Suffield Research Centre, Medicine Hat, AB, CanadaDefence Research and Development Canada, Toronto Research Centre, Toronto, ON, CanadaDefence Research and Development Canada, Toronto Research Centre, Toronto, ON, Canada1Canadian Forces Health Services, National Defence Headquarters, Ottawa, ON, Canada2Department of Psychiatry, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada3Department of Psychiatry, Faculty of Medicine, Dalhousie University, Halifax, NS, CanadaLawson Health Research Institute, London, ON, CanadaDepartment of Pediatrics, Western University, London, ON, CanadaNeurolytix Inc., Toronto, ON, Canada4Clinical Neurological Sciences, Western University, London, ON, Canada5Physiology and Pharmacology, Western University, London, ON, CanadaMilitary Breachers and Range Staff (MBRS) are subjected to repeated sub-concussive blasts, and they often report symptoms that are consistent with a mild traumatic brain injury (mTBI). Biomarkers of blast injury would potentially aid blast injury diagnosis, surveillance and avoidance. Our objective was to identify plasma metabolite biomarkers in military personnel that were exposed to repeated low-level or sub-concussive blast overpressure. A total of 37 military members were enrolled (18 MBRS and 19 controls), with MBRS having participated in 8–20 breaching courses per year, with a maximum exposure of 6 blasts per day. The two cohorts were similar except that the number of blast exposures were significantly higher in the MBRS, and the MBRS cohort suffered significantly more post-concussive symptoms and poorer health on assessment. Metabolomics profiling demonstrated significant differences between groups with 74% MBRS classification accuracy (CA). Feature reduction identified 6 metabolites that resulted in a MBRS CA of 98%, and included acetic acid (23.7%), formate (22.6%), creatine (14.8%), acetone (14.2%), methanol (12,7%), and glutamic acid (12.0%). All 6 metabolites were examined with individual receiver operating characteristic (ROC) curve analyses and demonstrated areas-under-the-curve (AUCs) of 0.82–0.91 (P ≤ 0.001) for MBRS status. Several parsimonious combinations of three metabolites increased accuracy of ROC curve analyses to AUCs of 1.00 (P < 0.001), while a combination of volatile organic compounds (VOCs; acetic acid, acetone and methanol) yielded an AUC of 0.98 (P < 0.001). Candidate biomarkers for chronic blast exposure were identified, and if validated in a larger cohort, may aid surveillance and care of military personnel. Future point-of-care screening could be developed that measures VOCs from breath, with definitive diagnoses confirmed with plasma metabolomics profiling.https://www.frontiersin.org/articles/10.3389/fneur.2022.831792/fullmilitaryblastmild traumatic brain injurymetabolitesbiomarkers |
| spellingShingle | Michael R. Miller Michael R. Miller Alicia DiBattista Alicia DiBattista Maitray A. Patel Mark Daley Mark Daley Catherine Tenn Ann Nakashima Shawn G. Rhind Shawn G. Rhind Oshin Vartanian Oshin Vartanian Maria Y. Shiu Norleen Caddy Michelle Garrett Doug Saunders Ingrid Smith Rakesh Jetly Rakesh Jetly Rakesh Jetly Douglas D. Fraser Douglas D. Fraser Douglas D. Fraser Douglas D. Fraser Douglas D. Fraser A Distinct Metabolite Signature in Military Personnel Exposed to Repetitive Low-Level Blasts Frontiers in Neurology military blast mild traumatic brain injury metabolites biomarkers |
| title | A Distinct Metabolite Signature in Military Personnel Exposed to Repetitive Low-Level Blasts |
| title_full | A Distinct Metabolite Signature in Military Personnel Exposed to Repetitive Low-Level Blasts |
| title_fullStr | A Distinct Metabolite Signature in Military Personnel Exposed to Repetitive Low-Level Blasts |
| title_full_unstemmed | A Distinct Metabolite Signature in Military Personnel Exposed to Repetitive Low-Level Blasts |
| title_short | A Distinct Metabolite Signature in Military Personnel Exposed to Repetitive Low-Level Blasts |
| title_sort | distinct metabolite signature in military personnel exposed to repetitive low level blasts |
| topic | military blast mild traumatic brain injury metabolites biomarkers |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2022.831792/full |
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