Complex Factors in the Etiology of Gulf War Illness: Wartime Exposures and Risk Factors in Veteran Subgroups

Background: At least one-fourth of U.S. veterans who served in the 1990–1991 Gulf War are affected by the chronic symptomatic illness known as Gulf War illness (GWI). Clear determination of the causes of GWI has been hindered by many factors, including limitations in how epidemiologic studies have assessed the impact of the complex deployment environment on veterans’ health

Butyrylcholinesterase genotype and enzyme activity in relation to Gulf War illness: preliminary evidence of gene-exposure interaction from a case¿control study of 1991 Gulf War veterans

Abstract Background Epidemiologic studies have implicated wartime exposures to acetylcholinesterase (AChE)-inhibiting chemicals as etiologic factors in Gulf War illness (GWI), the multisymptom condition linked to military service in the 1991 Gulf War. It is unclear, however, why some veterans developed GWI while others with similar exposures did not. Genetic variants of the enzyme butyrylcholinesterase (BChE) differ in their capacity for metabolizing AChE-inhibiting chemicals, and may confer differences in biological responses to these compounds. The current study assessed BChE enzyme activity and BChE genotype in 1991 Gulf War veterans to evaluate possible association of this enzyme with GWI. Methods This case–control study evaluated a population-based sample of 304 Gulf War veterans (144 GWI cases, meeting Kansas GWI criteria, and 160 controls). BChE enzyme activity levels and genotype were compared, overall, in GWI cases and controls. Potential differences in risk associated with cholinergic-related exposures in theater were explored using stratified analyses to compare associations between GWI and exposures in BChE genetic and enzyme activity subgroups. Results Overall, GWI cases and controls did not differ by mean BChE enzyme activity level or by BChE genotype. However, for the subgroup of Gulf War veterans with less common, generally less active, BChE genotypes (K/K, U/AK, U/A, A/F, AK/F), the association of wartime use of pyridostigmine bromide (PB) with GWI (OR = 40.00, p = 0.0005) was significantly greater than for veterans with the more common U/U and U/K genotypes (OR = 2.68, p = 0.0001). Conclusions Study results provide preliminary evidence that military personnel with certain BChE genotypes who used PB during the 1991 Gulf War may have been at particularly high risk for developing GWI. Genetic differences in response to wartime exposures are potentially important factors in GWI etiology and should be further evaluated in conjunction with exposure effects.Peer Reviewe

PON1 Status in Relation to Gulf War Illness: Evidence of Gene–Exposure Interactions from a Multisite Case–Control Study of 1990–1991 Gulf War Veterans

Background: Deployment-related neurotoxicant exposures are implicated in the etiology of Gulf War illness (GWI), the multisymptom condition associated with military service in the 1990–1991 Gulf War (GW). A Q/R polymorphism at position 192 of the paraoxonase (PON)-1 enzyme produce PON1192 variants with different capacities for neutralizing specific chemicals, including certain acetylcholinesterase inhibitors. Methods: We evaluated PON1192 status and GW exposures in 295 GWI cases and 103 GW veteran controls. Multivariable logistic regression determined independent associations of GWI with GW exposures overall and in PON1192 subgroups. Exact logistic regression explored effects of exposure combinations in PON1192 subgroups. Results: Hearing chemical alarms (proxy for possible nerve agent exposure) was associated with GWI only among RR status veterans (OR = 8.60, p = 0.014). Deployment-related skin pesticide use was associated with GWI only among QQ (OR = 3.30, p = 0.010) and QR (OR = 4.22, p < 0.001) status veterans. Exploratory assessments indicated that chemical alarms were associated with GWI in the subgroup of RR status veterans who took pyridostigmine bromide (PB) (exact OR = 19.02, p = 0.009) but not RR veterans who did not take PB (exact OR = 0.97, p = 1.00). Similarly, skin pesticide use was associated with GWI among QQ status veterans who took PB (exact OR = 6.34, p = 0.001) but not QQ veterans who did not take PB (exact OR = 0.59, p = 0.782). Conclusion: Study results suggest a complex pattern of PON1192 exposures and exposure–exposure interactions in the development of GWI

Association of atherosclerotic Cardiovascular Disease, Hypertension, Diabetes, and Hyperlipidemia With Gulf War Illness among Gulf War Veterans

BACKGROUND: Approximately 30% of the 700 000 Gulf War veterans report a chronic symptom-based illness of varying severity referred to as Gulf War illness (GWI). toxic deployment-related exposures have been implicated in the cause of GWI, some of which contribute to metabolic dysregulation and lipid abnormalities. As this cohort ages, the relationship between GWI and atherosclerotic cardiovascular disease (ASCVD) is a growing concern. We evaluated associations between GWI and ASCVD, diabetes, hyperlipidemia, and hypertension in veterans of the Gulf War (1990-1991). METHODS AND RESULTS: Analysis of survey data collected in 2014 to 2016 from a national sample of deployed Gulf War veterans (n=942) and Veterans Health Administration electronic health record data (n=669). Multivariable logistic regression models tested for associations of GWI with self-reported ASCVD, diabetes, hyperlipidemia, and hypertension, controlling for confounding factors. Separate models tested for GWI associations with ASCVD and risk factors documented in the electronic health record. GWI was associated with self-reported hypertension (adjusted odds ratio [aOR], 1.67 [95% CI, 1.18-2.36]), hyperlipidemia (aOR, 1.46 [95% CI, 1.03-2.05]), and ASCVD (aOR, 2.65 [95% CI, 1.56-4.51]). In the subset of veterans with electronic health record data, GWI was associated with documented diabetes (aOR, 2.34 [95% CI, 1.43-3.82]) and hypertension (aOR, 2.84 [95% CI, 1.92-4.20]). Hyperlipidemia and hypertension served as partial mediators of the association between GWI and self-reported ASCVD. CONCLUSIONS: Gulf War veterans with GWI had higher odds of hyperlipidemia, hypertension, diabetes, and ASCVD compared with Gulf War veterans without GWI. Further examination of the mechanisms underlying this association, including a possible shared exposure-related mechanism, is necessary

Young adults and the 5 a day campaign: perceived benefits and barriers of eating more fruits and vegetables

Although consuming adequate amounts of fruits and vegetables reduces the risk of developing chronic diseases, it is widely recognized that young adults’ intakes are currently well below the Department of Health’s recommended five portions a day, with men consuming even less than women. One approach in the UK has been to introduce health campaigns such as the 5 A DAY programme; however, little is currently known about how well their messages are understood amongst young adults. This study examined current knowledge of the 5 A DAY message in young adults, as well as the perceived benefits and remaining barriers towards consuming more fruits and vegetables. In total, four focus groups were conducted using male (n = 22) and female (n = 18) students at the University of Reading. Content analysis revealed that while participants were aware of the 5 A DAY recommendation, there was widespread confusion regarding the detail. In addition, men were less accepting of the message than women, reporting greater disbelief and a lack of motivation to increase intake. Finally, a range of barriers was reported by participants of both genders, despite the perceived beneficial effects for health and appearance. The results illustrate a considerable gap between awareness and knowledge of the 5 A DAY message, and underscore the challenge that changing behaviour in young adults represents. As well as stepping up education- and skill-based health campaigns, more targeted gender specific interventions will be needed to achieve sustained increases in fruit and vegetable intake

Skill learning strengthens cortical representations of motor sequences.

Motor-skill learning can be accompanied by both increases and decreases in brain activity. Increases may indicate neural recruitment, while decreases may imply that a region became unimportant or developed a more efficient representation of the skill. These overlapping mechanisms make interpreting learning-related changes of spatially averaged activity difficult. Here we show that motor-skill acquisition is associated with the emergence of highly distinguishable activity patterns for trained movement sequences, in the absence of average activity increases. During functional magnetic resonance imaging, participants produced either four trained or four untrained finger sequences. Using multivariate pattern analysis, both untrained and trained sequences could be discriminated in primary and secondary motor areas. However, trained sequences were classified more reliably, especially in the supplementary motor area. Our results indicate skill learning leads to the development of specialized neuronal circuits, which allow the execution of fast and accurate sequential movements without average increases in brain activity. DOI:http://dx.doi.org/10.7554/eLife.00801.001

The prevalence of mild cognitive impairment in Gulf War veterans: a follow-up study

IntroductionGulf War Illness (GWI), also called Chronic Multisymptom Illness (CMI), is a multi-faceted condition that plagues an estimated 250,000 Gulf War (GW) veterans. Symptoms of GWI/CMI include fatigue, pain, and cognitive dysfunction. We previously reported that 12% of a convenience sample of middle aged (median age 52 years) GW veterans met criteria for mild cognitive impairment (MCI), a clinical syndrome most prevalent in older adults (e.g., ≥70 years). The current study sought to replicate and extend this finding.MethodsWe used the actuarial neuropsychological criteria and the Montreal Cognitive Assessment (MoCA) to assess the cognitive status of 952 GW veterans. We also examined regional brain volumes in a subset of GW veterans (n = 368) who had three Tesla magnetic resonance images (MRIs).ResultsWe replicated our previous finding of a greater than 10% rate of MCI in four additional cohorts of GW veterans. In the combined sample of 952 GW veterans (median age 51 years at time of cognitive testing), 17% met criteria for MCI. Veterans classified as MCI were more likely to have CMI, history of depression, and prolonged (≥31 days) deployment-related exposures to smoke from oil well fires and chemical nerve agents compared to veterans with unimpaired and intermediate cognitive status. We also replicated our previous finding of hippocampal atrophy in veterans with MCI, and found significant group differences in lateral ventricle volumes.DiscussionBecause MCI increases the risk for late-life dementia and impacts quality of life, it may be prudent to counsel GW veterans with cognitive dysfunction, CMI, history of depression, and high levels of exposures to deployment-related toxicants to adopt lifestyle habits that have been associated with lowering dementia risk. With the Food and Drug Administration’s recent approval of and the VA’s decision to cover the cost for anti-amyloid β (Aβ) therapies, a logical next step for this research is to determine if GW veterans with MCI have elevated Aβ in their brains

On the nature and variability of the east Greenland Spill Jet : a case study in Summer 2003

Author Posting. © American Meteorological Society, 2011. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 41 (2011): 2307–2327, doi:10.1175/JPO-D-10-05004.1.Results from a high-resolution (~2 km) numerical simulation of the Irminger Basin during summer 2003 are presented. The focus is on the East Greenland Spill Jet, a recently discovered component of the circulation in the basin. The simulation compares well with observations of surface fields, the Denmark Strait overflow (DSO), and the hydrographic structure of typical sections in the basin. The model reveals new aspects of the circulation on scales of O(0.1–10) days and O(1–100) km. The model Spill Jet results from the cascade of dense waters over the East Greenland shelf. Spilling can occur in various locations southwest of the strait, and it is present throughout the simulation but exhibits large variations on periods of O(0.1–10) days. The Spill Jet sometimes cannot be distinguished in the velocity field from surface eddies or from the DSO. The vorticity structure of the jet confirms its unstable nature with peak relative and tilting vorticity terms reaching twice the planetary vorticity term. The average model Spill Jet transport is 4.9 ±1.7 Sv (1 Sv ≡ 106 m3 s−1) equatorward, about 2½ times larger than has been previously reported from a single ship transect in August 2001. Kinematic analysis of the model results suggests two different types of spilling events. In the first case (type I), a local perturbation results in dense waters descending over the shelf break into the Irminger Basin. In the second case (type II), surface cyclones associated with DSO deep domes initiate the spilling process. During summer 2003, more than half of the largest Spill Jet transport values are of type II.The research is supported by the National Science Foundation Grants OCE-0726393 and OCI-0904640 (MGM and TWNH) and OCE-0726640 (RSP).2012-06-0

Neuroimaging markers for studying Gulf-War illness: single-subject level analytical method based on machine learning

Gulf War illness (GWI) refers to the multitude of chronic health symptoms, spanning from fatigue, musculoskeletal pain, and neurological complaints to respiratory, gastrointestinal, and dermatologic symptoms experienced by about 250,000 GW veterans who served in the 1991 Gulf War (GW). Longitudinal studies showed that the severity of these symptoms often remain unchanged even years after the GW, and these veterans with GWI continue to have poorer general health and increased chronic medical conditions than their non-deployed counterparts. For better management and treatment of this condition, there is an urgent need for developing objective biomarkers that can help with simple and accurate diagnosis of GWI. In this study, we applied multiple neuroimaging techniques, including T1-weighted magnetic resonance imaging (T1W-MRI), diffusion tensor imaging (DTI), and novel neurite density imaging (NDI) to perform both a group-level statistical comparison and a single-subject level machine learning (ML) analysis to identify diagnostic imaging features of GWI. Our results supported NDI as the most sensitive in defining GWI characteristics. In particular, our classifier trained with white matter NDI features achieved an accuracy of 90% and F-score of 0.941 for classifying GWI cases from controls after the cross-validation. These results are consistent with our previous study which suggests that NDI measures are sensitive to the microstructural and macrostructural changes in the brain of veterans with GWI, which can be valuable for designing better diagnosis method and treatment efficacy studies.W81XWH-17-1-0440 - a department of Defense CDMRP new investigator awardPublished versio