Bioenergetic impairment in Gulf War illness assessed via 31P-MRS

Abstract Time for post-exercise phosphocreatine-recovery (PCr-R), deemed a robust index of mitochondrial function in vivo, was previously reported to be elevated (signifying impaired ATP production) in veterans with Gulf War illness (GWI). Here we sought to replicate the finding and assess the impac...

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Main Authors: Beatrice Alexandra Golomb, Jun Hee Han, Alexander Fung, Brinton Keith Berg, Bruce J. Miller, Gavin Hamilton
Format: Article
Language:English
Published: Nature Portfolio 2024-03-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-024-57725-4
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author Beatrice Alexandra Golomb
Jun Hee Han
Alexander Fung
Brinton Keith Berg
Bruce J. Miller
Gavin Hamilton
author_facet Beatrice Alexandra Golomb
Jun Hee Han
Alexander Fung
Brinton Keith Berg
Bruce J. Miller
Gavin Hamilton
author_sort Beatrice Alexandra Golomb
collection DOAJ
description Abstract Time for post-exercise phosphocreatine-recovery (PCr-R), deemed a robust index of mitochondrial function in vivo, was previously reported to be elevated (signifying impaired ATP production) in veterans with Gulf War illness (GWI). Here we sought to replicate the finding and assess the impact of contravening previous eligibility requirements. The replication sample comprised white males. Cases reported ≥ moderate muscle-weakness to match the organ assessed to an organ affected; controls lacked recent headache or multiple symptoms. The expansion sample added cases without muscle-weakness, controls with recent headache, females, nonwhites. PCr-R, following pedal-depression-exercise, was compared in veterans with GWI versus controls (sample N = 38). In the replication sample, PCr-R results closely matched the prior report: PCr-R veterans with GWI mean(SD) = 47.7(16.5); control mean(SD) = 30.3(9.2), p = 0.017. (Prior-study PCr-R veterans with GWI mean(SD) = 46.1(17.9), control mean(SD) = 29.0(8.7), p = 0.023. Combined replication + prior samples: p = 0.001.) No case–control difference was observed in the expansion sample. In cases, PCr-R related to muscle-weakness: PCr-R = 29.9(7.1), 38.2(8.9), 47.8(15.2) for muscle-weakness rated none/low, intermediate, and high respectively (p for trend = 0.02), validating desirability of matching tissue assessed to tissue affected. In controls, headache/multiple symptoms, sex, and ethnicity each mattered (affecting PCr-R significantly). This study affirms mitochondrial/bioenergetic impairment in veterans with GWI. The importance of careful case/control selection is underscored.
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spelling doaj.art-5d8541d66c2f49a2828a2de095da11b02024-03-31T11:17:43ZengNature PortfolioScientific Reports2045-23222024-03-0114111010.1038/s41598-024-57725-4Bioenergetic impairment in Gulf War illness assessed via 31P-MRSBeatrice Alexandra Golomb0Jun Hee Han1Alexander Fung2Brinton Keith Berg3Bruce J. Miller4Gavin Hamilton5Department of Medicine, University of California, San DiegoDepartment of Medicine, University of California, San DiegoDepartment of Medicine, University of California, San DiegoDepartment of Medicine, University of California, San DiegoDepartment of Medicine, University of California, San DiegoDepartment of Radiology, University of California, San DiegoAbstract Time for post-exercise phosphocreatine-recovery (PCr-R), deemed a robust index of mitochondrial function in vivo, was previously reported to be elevated (signifying impaired ATP production) in veterans with Gulf War illness (GWI). Here we sought to replicate the finding and assess the impact of contravening previous eligibility requirements. The replication sample comprised white males. Cases reported ≥ moderate muscle-weakness to match the organ assessed to an organ affected; controls lacked recent headache or multiple symptoms. The expansion sample added cases without muscle-weakness, controls with recent headache, females, nonwhites. PCr-R, following pedal-depression-exercise, was compared in veterans with GWI versus controls (sample N = 38). In the replication sample, PCr-R results closely matched the prior report: PCr-R veterans with GWI mean(SD) = 47.7(16.5); control mean(SD) = 30.3(9.2), p = 0.017. (Prior-study PCr-R veterans with GWI mean(SD) = 46.1(17.9), control mean(SD) = 29.0(8.7), p = 0.023. Combined replication + prior samples: p = 0.001.) No case–control difference was observed in the expansion sample. In cases, PCr-R related to muscle-weakness: PCr-R = 29.9(7.1), 38.2(8.9), 47.8(15.2) for muscle-weakness rated none/low, intermediate, and high respectively (p for trend = 0.02), validating desirability of matching tissue assessed to tissue affected. In controls, headache/multiple symptoms, sex, and ethnicity each mattered (affecting PCr-R significantly). This study affirms mitochondrial/bioenergetic impairment in veterans with GWI. The importance of careful case/control selection is underscored.https://doi.org/10.1038/s41598-024-57725-4Gulf War illnessMitochondrial31P-MRSPhosphocreatineBioenergeticsGender differences
spellingShingle Beatrice Alexandra Golomb
Jun Hee Han
Alexander Fung
Brinton Keith Berg
Bruce J. Miller
Gavin Hamilton
Bioenergetic impairment in Gulf War illness assessed via 31P-MRS
Scientific Reports
Gulf War illness
Mitochondrial
31P-MRS
Phosphocreatine
Bioenergetics
Gender differences
title Bioenergetic impairment in Gulf War illness assessed via 31P-MRS
title_full Bioenergetic impairment in Gulf War illness assessed via 31P-MRS
title_fullStr Bioenergetic impairment in Gulf War illness assessed via 31P-MRS
title_full_unstemmed Bioenergetic impairment in Gulf War illness assessed via 31P-MRS
title_short Bioenergetic impairment in Gulf War illness assessed via 31P-MRS
title_sort bioenergetic impairment in gulf war illness assessed via 31p mrs
topic Gulf War illness
Mitochondrial
31P-MRS
Phosphocreatine
Bioenergetics
Gender differences
url https://doi.org/10.1038/s41598-024-57725-4
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