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BACKGROUND: Veterans of the first Gulf War (1990-1991) are reaching middle and older adulthood in differing degrees of health and biological age. Many Gulf War veterans report myriad negative symptoms classified as Gulf War illness (GWI), a chronic multi-symptom illness. OBJECTIVES: To describe and analyze deficit accumulation, among veterans with Severe GWI (SGWI+) and those without Severe GWI (SGWI-), to assess the association between a medically unexplained illness and aging. DESIGN: This study uses a retrospective cohort design with quasi-longitudinal data. SETTING: The recruitment sample included 10,042 Gulf War era veterans across all four US Census regions. PARTICIPANTS: The analytic sample included 1,054 participants of the GWECB for whom SGWI case status could be determined and who had valid responses for at least 90% of the deficits included in the deficit accumulation index. MEASUREMENTS: Chronic health conditions were retroactively reported, including year of diagnosis, enabling us to create a longitudinal measure of deficit accumulation. This deficit accumulation index (DAI) ranged from 0-1 for each respondent in each year between 1991-2013. We compare veterans with SGWI+ to those with SGWI- using the CDC case definition. RESULTS: Most veterans in our sample could expect to spend more years with moderate or substantial deficits than without deficits. SGWI+ was associated with spending more years with substantial deficits than those with SGWI-. Veterans in middle age (age 35-65) experienced more years with substantial deficits than younger veterans. Individuals with SGWI+ had 13 times the hazard of accumulating substantial deficits than those without. CONCLUSIONS: This study demonstrated that veterans with SGWI+, even those in midlife, experienced aging as measured by accumulating deficits. Practitioners should consider patients with multi-symptom illnesses as at risk of accelerated aging, tailoring treatments to address patients' holistic needs.
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Guerra del Golfo , Síndrome del Golfo Pérsico , Veteranos , Humanos , Veteranos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Síndrome del Golfo Pérsico/epidemiología , Anciano , Estados Unidos/epidemiología , Estudios Longitudinales , Envejecimiento/fisiología , AdultoRESUMEN
Effective surveillance on the long-term public health impact due to war and terrorist attacks remains limited. Such health issues are commonly under-reported, specifically for a large group of individuals. For this purpose, efficient estimation of the size or undercount of the population under the risk of physical and mental health hazards is of utmost necessity. A novel trivariate Bernoulli model is developed allowing heterogeneity among the individuals and dependence between the sources of information, and an estimation methodology using a Monte Carlo-based EM algorithm is proposed. Simulation results show the superiority of the performance of the proposed method over existing competitors and robustness under model mis-specifications. The method is applied to analyse two real case studies on monitoring amyotrophic lateral sclerosis (ALS) cases for the Gulf War veterans and the 9/11 terrorist attack survivors at the World Trade Center, USA. The average annual cumulative incidence rate for ALS disease increases by 33 % and 16 % for deployed and no-deployed military personnel, respectively, after adjusting the undercount. The number of individuals exposed to the risk of physical and mental health effects due to WTC terrorist attacks increased by 42 % . These results provide interesting insights that can assist in effective decision-making and policy formulation for monitoring the health status of post-war survivors.
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Esclerosis Amiotrófica Lateral , Humanos , Prevalencia , Esclerosis Amiotrófica Lateral/epidemiología , Veteranos/estadística & datos numéricos , Algoritmos , Método de Montecarlo , Guerra del GolfoRESUMEN
Objective: Gulf War Illness (GWI) is a debilitating multisymptom condition that affects nearly a third of 1990-91 Gulf War (GW) veterans. Symptoms include pain, fatigue, gastrointestinal issues, and cognitive decrements. Our work has shown that GWI rates and potential causes for symptoms vary between men and women veterans. Studies have documented neuropsychological and neuroimaging findings mostly in men or combined sex datasets. Data are lacking for women veterans due to lack of power and repositories of women veteran samples. Methods: We characterized GW women veterans in terms of demographics, exposures, neuropsychological and neuroimaging outcomes from the newly collated Boston, Biorepository and Integrative Network (BBRAIN) for GWI. Results: BBRAIN women veterans are highly educated with an average age of 54 years. 81% met GWI criteria, 25% met criteria for current PTSD, 78% were white, and 81% served in the Army. Exposure to combined acetylcholinesterase inhibitors (AChEi) including skin pesticides, fogs/sprays and/or pyridostigmine bromide (PB) anti-nerve gas pill exposure resulted in slower processing speed on attentional tasks and a trend for executive impairment compared with non-exposed women. Brain imaging outcomes showed lower gray matter volumes and smaller caudate in exposed women. Conclusions: Although subtle and limited findings were present in this group of women veterans, it suggests that continued follow-up of GW women veterans is warranted. Future research should continue to evaluate differences between men and women in GW veteran samples. The BBRAIN women sub-repository is recruiting and these data are available to the research community for studies of women veterans.
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Neuroimagen , Síndrome del Golfo Pérsico , Veteranos , Humanos , Femenino , Persona de Mediana Edad , Síndrome del Golfo Pérsico/diagnóstico por imagen , Guerra del Golfo , Adulto , Boston/epidemiología , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Pruebas Neuropsicológicas , Imagen por Resonancia Magnética , Trastornos por Estrés Postraumático/diagnóstico por imagen , AncianoRESUMEN
BACKGROUND: One-third of veterans returning from the 1990-1991 Gulf War reported a myriad of symptoms including cognitive dysfunction, skin rashes, musculoskeletal discomfort, and fatigue. This symptom cluster is now referred to as Gulf War Illness (GWI). As the underlying mechanisms of GWI have yet to be fully elucidated, diagnosis and treatment are based on symptomatic presentation. One confounding factor tied to the illness is the high presence of post-traumatic stress disorder (PTSD). Previous research efforts have demonstrated that both GWI and PTSD are associated with immunological dysfunction. As such, this research endeavor aimed to provide insight into the complex relationship between GWI symptoms, cytokine presence, and immune cell populations to pinpoint the impact of PTSD on these measures in GWI. METHODS: Symptom measures were gathered through the Multidimensional fatigue inventory (MFI) and 36-item short form health survey (SF-36) scales and biological measures were obtained through cytokine & cytometry analysis. Subgrouping was conducted using Davidson Trauma Scale scores and the Structured Clinical Interview for Diagnostic and statistical manual of mental disorders (DSM)-5, into GWI with high probability of PTSD symptoms (GWIH) and GWI with low probability of PTSD symptoms (GWIL). Data was analyzed using Analysis of variance (ANOVA) statistical analysis along with correlation graph analysis. We mapped correlations between immune cells and cytokine signaling measures, hormones and GWI symptom measures to identify patterns in regulation between the GWIH, GWIL, and healthy control groups. RESULTS: GWI with comorbid PTSD symptoms resulted in poorer health outcomes compared with both Healthy control (HC) and the GWIL subgroup. Significant differences were found in basophil levels of GWI compared with HC at peak exercise regardless of PTSD symptom comorbidity (ANOVA F = 4.7, P = 0.01,) indicating its potential usage as a biomarker for general GWI from control. While the unique identification of GWI with PTSD symptoms was less clear, the GWIL subgroup was found to be delineated from both GWIH and HC on measures of IL-15 across an exercise challenge (ANOVA F > 3.75, P < 0.03). Additional differences in natural killer (NK) cell numbers and function highlight IL-15 as a potential biomarker of GWI in the absence of PTSD symptoms. CONCLUSION: We conclude that disentangling GWI and PTSD by defining trauma-based subgroups may aid in the identification of unique GWI biosignatures that can help to improve diagnosis and target treatment of GWI more effectively.
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Síndrome del Golfo Pérsico , Trastornos por Estrés Postraumático , Veteranos , Humanos , Masculino , Trastornos por Estrés Postraumático/complicaciones , Trastornos por Estrés Postraumático/epidemiología , Interleucina-15 , Guerra del Golfo , Citocinas , Síndrome del Golfo Pérsico/complicaciones , Biomarcadores , FatigaRESUMEN
To address gaps in understanding the pathophysiology of Gulf War Illness (GWI), the VA Million Veteran Program (MVP) developed and implemented a survey to MVP enrollees who served in the U.S. military during the 1990-1991 Persian Gulf War (GW). Eligible Veterans were invited via mail to complete a survey assessing health conditions as well as GW-specific deployment characteristics and exposures. We evaluated the representativeness of this GW-era cohort relative to the broader population by comparing demographic, military, and health characteristics between respondents and non-respondents, as well as with all GW-era Veterans who have used Veterans Health Administration (VHA) services and the full population of U.S. GW-deployed Veterans. A total of 109,976 MVP GW-era Veterans were invited to participate and 45,270 (41%) returned a completed survey. Respondents were 84% male, 72% White, 8% Hispanic, with a mean age of 61.6 years (SD = 8.5). Respondents were more likely to be older, White, married, better educated, slightly healthier, and have higher socioeconomic status than non-respondents, but reported similar medical conditions and comparable health status. Although generally similar to all GW-era Veterans using VHA services and the full population of U.S. GW Veterans, respondents included higher proportions of women and military officers, and were slightly older. In conclusion, sample characteristics of the MVP GW-era cohort can be considered generally representative of the broader GW-era Veteran population. The sample represents the largest research cohort of GW-era Veterans established to date and provides a uniquely valuable resource for conducting in-depth studies to evaluate health conditions affecting 1990-1991 GW-era Veterans.
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Personal Militar , Veteranos , Humanos , Femenino , Masculino , Persona de Mediana Edad , Guerra del Golfo , Estado de Salud , Encuestas EpidemiológicasRESUMEN
BACKGROUND: Gulf War illness (GWI)/Chronic Multisymptom Illness (CMI) is a disorder related to military service in the 1991 Gulf War (GW). Prominent symptoms of GWI/CMI include fatigue, pain, and cognitive dysfunction. Although anosmia is not a typical GWI/CMI symptom, anecdotally some GW veterans have reported losing their sense smell shortly after the war. Because olfactory deficit is a prodromal symptom of neurodegenerative diseases like Parkinson's and Alzheimer's disease, and because we previously reported suggestive evidence that deployed GW veterans may be at increased risk for Mild Cognitive Impairment (MCI) and dementia, the current study examined the relationship between olfactory and cognitive function in deployed GW veterans. METHODS: Eighty deployed GW veterans (mean age: 59.9 ±7.0; 4 female) were tested remotely with the University of Pennsylvania Smell Identification Test (UPSIT) and the Montreal Cognitive Assessment (MoCA). Veterans also completed self-report questionnaires about their health and deployment-related exposures and experiences. UPSIT and MoCA data from healthy control (HC) participants from the Parkinson's Progression Markers Initiative (PPMI) study were downloaded for comparison. RESULTS: GW veterans had a mean UPSIT score of 27.8 ± 6.3 (range 9-37) and a mean MoCA score of 25.3 ± 2.8 (range 19-30). According to age- and sex-specific normative data, 31% of GW veterans (vs. 8% PPMI HCs) had UPSIT scores below the 10th percentile. Nearly half (45%) of GW veterans (vs. 8% PPMI HCs) had MoCA scores below the cut-off for identifying MCI. Among GW veterans, but not PPMI HCs, there was a positive correlation between UPSIT and MoCA scores (Spearman's ρ = 0.39, p < 0.001). There were no significant differences in UPSIT or MoCA scores between GW veterans with and without history of COVID or between those with and without Kansas GWI exclusionary conditions. CONCLUSIONS: We found evidence of olfactory and cognitive deficits and a significant correlation between UPSIT and MoCA scores in a cohort of 80 deployed GW veterans, 99% of whom had CMI. Because impaired olfactory function has been associated with increased risk for MCI and dementia, it may be prudent to screen aging, deployed GW veterans with smell identification tests so that hypo- and anosmic veterans can be followed longitudinally and offered targeted neuroprotective therapies as they become available.
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Demencia , Enfermedad de Parkinson , Síndrome del Golfo Pérsico , Veteranos , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , Guerra del Golfo , Olfato , Síndrome del Golfo Pérsico/epidemiología , Síndrome del Golfo Pérsico/complicaciones , CogniciónRESUMEN
INTRODUCTION: Alcohol use disorder (AUD) is prevalent among veterans, and excessive alcohol use is associated with significant mental and physical health consequences. Currently, the largest cohort of veterans seeking services at the VA are those from the 1990s Gulf War Era. This cohort of veterans is unique due to the nature of their deployment resulting in a myriad of unexplained symptoms collectively known as "Gulf War Illness" and higher rates of mental health problems. The present study sought to examine the association between probable AUD and mental health treatment utilization in a sample of 1126 (882 male) Gulf War-era veterans. METHODS: Veterans completed a self-report survey including the AUDIT-C, questions about mental health treatment engagement, and demographic questions. RESULTS: Results demonstrated that approximately 20 % of the sample screened positive for probable AUD, determined by standard AUDIT-C cutoff scores. Among those screening positive for AUD, 25 % reported engaging in mental health treatment in the past year. Veterans with probable AUD who use VA care had 3.8 times the odds of receiving mental health services than veterans not using VA care. Use of mental health services was associated with mental health comorbidity and identifying as Black/African American. CONCLUSIONS: The results of the present study highlight a significant unmet need for mental health treatment among Gulf War-era veterans with AUD.
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Alcoholismo , Guerra del Golfo , Servicios de Salud Mental , Veteranos , Humanos , Masculino , Veteranos/psicología , Veteranos/estadística & datos numéricos , Servicios de Salud Mental/estadística & datos numéricos , Femenino , Persona de Mediana Edad , Adulto , Alcoholismo/epidemiología , Alcoholismo/terapia , Alcoholismo/psicología , Estados Unidos/epidemiología , Aceptación de la Atención de Salud/estadística & datos numéricos , Aceptación de la Atención de Salud/psicologíaRESUMEN
Approximately one-third of Gulf War veterans suffer from Gulf War Illness (GWI), which encompasses mood disorders and depressive symptoms. Deployment-related exposure to organophosphate compounds has been associated with GWI development. Epigenetic modifications have been reported in GWI veterans. We previously showed that epigenetic histone dysregulations were associated with decreased brain-derived neurotrophic factor (BDNF) expression in a GWI rat model. GWI has no effective therapies. Ketamine (KET) has recently been approved by the Food and Drug Administration for therapy-resistant depression. Interestingly, BDNF upregulation underlies KET's antidepressant effect in GWI-related depression. Here, we investigated whether KET's effect on histone mechanisms signals BDNF upregulations in GWI. Male Sprague-Dawley rats were injected once daily with diisopropyl fluorophosphate (DFP; 0.5 mg/kg, s.c., 5 days). At 6 months following DFP exposure, KET (10 mg/kg, i.p.) was injected, and brains were dissected 24 hours later. Western blotting was used for protein expression, and epigenetic studies used chromatin immunoprecipitation methods. Dil staining was conducted for assessing dendritic spines. Our results indicated that an antidepressant dose of KET inhibited the upregulation of histone deacetylase (HDAC) enzymes in DFP rats. Furthermore, KET restored acetylated histone occupancy at the Bdnf promoter IV and induced BDNF protein expression in DFP rats. Finally, KET treatment also increased the spine density and altered the spine diversity with increased T-type and decreased S-type spines in DFP rats. Given these findings, we propose that KET's actions involve the inhibition of HDAC expression, upregulation of BDNF, and dendritic modifications that together ameliorates the pathologic synaptic plasticity and exerts an antidepressant effect in DFP rats. SIGNIFICANCE STATEMENT: This study offers evidence supporting the involvement of epigenetic histone pathways in the antidepressant effects of ketamine (KET) in a rat model of Gulf War Illness (GWI)-like depression. This effect is achieved through the modulation of histone acetylation at the Bdnf promoter, resulting in elevated brain-derived neurotrophic factor expression and subsequent dendritic remodeling in the hippocampus. These findings underscore the rationale for considering KET as a potential candidate for clinical trials aimed at managing GWI-related depression.
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Fluoruros , Ketamina , Síndrome del Golfo Pérsico , Fosfatos , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Ketamina/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Guerra del Golfo , Síndrome del Golfo Pérsico/inducido químicamente , Síndrome del Golfo Pérsico/metabolismo , Síndrome del Golfo Pérsico/patología , Histonas , Hipocampo , Antidepresivos/efectos adversosRESUMEN
Operations Desert Shield and Storm occurred over 30 years ago, yet many of those who were deployed continue to experience chronic and debilitating symptoms, now recognized as Gulf War Illness (GWI). While efforts have been made to explore clinical treatments for GWI, misperceptions and skepticism about its complex nature and a lack of consensus on its etiology impede progress in this area. A critical necessity remains to better understand the experiences, needs, and concerns of veterans with GWI. In this qualitative research study, 40 Gulf War veterans were interviewed about their perceptions regarding symptoms of physical health, cognitive functioning, quality of life, and the quality of care received. In addition, they depicted their experiences through an artistic elicitation collage. Through a grounded theory method, key findings indicated that there are remaining hurdles, such as challenging symptoms, persisting unknowns about the illness, and variations in treatment quality. Veterans have mostly managed and coped with GWI, but they voice the need for acknowledgment and support. The main implication from this study is the significance of both clinical and institutional validation and recognition of the GWI experience as well as the need for specific support systems.
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Síndrome del Golfo Pérsico , Veteranos , Humanos , Veteranos/psicología , Síndrome del Golfo Pérsico/etiología , Síndrome del Golfo Pérsico/terapia , Guerra del Golfo , Calidad de VidaRESUMEN
BACKGROUND: To examine ocular symptoms and signs of veterans with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) diagnosis, ME/CFS symptoms, and controls. METHODS: This was a prospective, cross-sectional study of 124 South Florida veterans in active duty during the Gulf War era. Participants were recruited at an ophthalmology clinic at the Miami Veterans Affairs Hospital and evaluated for a diagnosis of ME/CFS, or symptoms of ME/CFS (intermediate fatigue, IF) using the Canadian Consensus criteria. Ocular symptoms were assessed via standardised questionnaires and signs via comprehensive slit lamp examination. Inflammatory blood markers were analysed and compared across groups. RESULTS: Mean age was 55.1 ± 4.7 years, 88.7% identified as male, 58.1% as White, and 39.5% as Hispanic. Ocular symptoms were more severe in the ME/CFS (n = 32) and IF (n = 48) groups compared to controls (n = 44) across dry eye (DE; Ocular Surface Disease Index [OSDI]: 48.9 ± 22.3 vs. 38.8 ± 23.3 vs. 19.1 ± 17.8, p < 0.001; 5 item Dry Eye Questionnaire [DEQ-5]: 10.8 ± 3.9 vs. 10.0 ± 4.6 vs. 6.6 ± 4.2, p < 0.001) and pain-specific questionnaires (Numerical Rating Scale 1-10 [NRS] right now: 2.4 ± 2.8 vs. 2.4 ± 2.9 vs 0.9 ± 1.5; p = 0.007; Neuropathic Pain Symptom Inventory modified for the Eye [NPSI-E]: 23.0 ± 18.6 vs. 19.8 ± 19.1 vs. 6.5 ± 9.0, p < 0.001). Ocular surface parameters and blood markers of inflammation were generally similar across groups. CONCLUSION: Individuals with ME/CFS report increased ocular pain but similar DE signs, suggesting that mechanisms beyond the ocular surface contribute to symptoms.
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Síndromes de Ojo Seco , Síndrome de Fatiga Crónica , Veteranos , Humanos , Masculino , Estados Unidos/epidemiología , Persona de Mediana Edad , Síndrome de Fatiga Crónica/diagnóstico , Síndrome de Fatiga Crónica/epidemiología , Estudios Transversales , Estudios Prospectivos , Guerra del Golfo , Canadá , Síndromes de Ojo Seco/diagnóstico , Síndromes de Ojo Seco/epidemiología , DolorRESUMEN
Gulf War illness (GWI) is a chronic multisymptom disorder of unknown etiology that is believed to be caused by neurotoxicant exposure experienced during deployment to the Gulf War. Posttraumatic stress disorder (PTSD) covaries with GWI and is believed to play a role in GWI symptoms. The present study examined the association between self-reported military exposures and GWI, stratified by PTSD status, in veterans from the Gulf War Era Cohort and Biorepository who were deployed to the Persian Gulf during the war. Participants self-reported current GWI and PTSD symptoms as well as military exposures (e.g., pyridostigmine [PB] pills, pesticides/insecticides, combat, chemical attacks, and oil well fires) experienced during the Gulf War. Deployed veterans' (N = 921) GWI status was ascertained using the Centers for Disease Control and Prevention definition. Individuals who met the GWI criteria were stratified by PTSD status, yielding three groups: GWI-, GWI+/PTSD-, and GWI+/PTSD+. Multivariable logistic regression, adjusted for covariates, was used to examine associations between GWI/PTSD groups and military exposures. Apart from insect bait use, the GWI+/PTSD+ group had higher odds of reporting military exposures than the GWI+/PTSD- group, adjusted odds ratio (aOR) = 2.15, 95% CI [1.30, 3.56]-aOR = 6.91, 95% CI [3.39, 14.08]. Except for PB pills, the GWI+/PTSD- group had a higher likelihood of reporting military exposures than the GWI- group, aOR = 2.03, 95% CI [1.26, 3.26]-aOR = 4.01, 95% CI [1.57, 10.25]. These findings are consistent with roles for both PTSD and military exposures in the etiology of GWI.
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Personal Militar , Síndrome del Golfo Pérsico , Trastornos por Estrés Postraumático , Veteranos , Humanos , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/complicaciones , Síndrome del Golfo Pérsico/epidemiología , Síndrome del Golfo Pérsico/etiología , Guerra del GolfoRESUMEN
Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting approximately 30 % of Veterans deployed to the Persian Gulf from 1990 to 91. GWI encompasses a wide spectrum of symptoms which frequently include neurological problems such as learning and memory impairments, mood disorders, and an increased incidence of neurodegenerative disorders. Combined exposure to both reversible and irreversible acetylcholinesterase (AChE) inhibitors has been identified as a likely risk factor for GWI. It is possible that the exposures affected connectivity in the brain, and it was also unknown whether this could benefit from treatment. We assessed chronic changes in dendritic architecture in granule cells of the dentate gyrus following exposure to pyridostigmine bromide (PB, 0.7 mg/kg), chlorpyrifos (CPF, 12.5 mg/kg), and N,N-diethyl-m-toluamide (DEET, 7.5 mg/kg) in male C57Bl/6J mice. We also evaluated the therapeutic effects of dietary administration for eight weeks of 1 % tert-butylhydroquinone (tBHQ), a Nrf2 activator, on long-term neuronal morphology. We found that Gulf War toxicant exposure resulted in reduced dendritic length and branching as well as overall spine density in dentate granule cells at 14 weeks post-exposure and that these effects were ameliorated by treatment with tBHQ. These findings indicate that Gulf War toxicant exposure results in chronic changes to dentate granule cell morphology and that modulation of neuroprotective transcription factors such as Nrf2 may improve long-term neuronal health in the hippocampus.
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Factor 2 Relacionado con NF-E2 , Síndrome del Golfo Pérsico , Ratones , Animales , Masculino , Acetilcolinesterasa , Guerra del Golfo , Síndrome del Golfo Pérsico/tratamiento farmacológico , Síndrome del Golfo Pérsico/inducido químicamente , Inhibidores de la Colinesterasa/farmacología , Encéfalo , Modelos Animales de EnfermedadRESUMEN
OBJECTIVES: Obstructive sleep apnea (OSA) among veterans is frequently underdiagnosed and undertreated. The present study sought to: 1) characterize the prevalence and rate of treatment of OSA among VA users and non-users and 2) examine the associations between diagnosed or probable OSA and key physical and mental health outcomes. METHODS: Gulf-War I-era Veterans were recruited as part of a national survey assessing mental and physical health concerns, healthcare needs, and healthcare utilization. OSA diagnoses were self-reported while sleep apnea risk was assessed via the STOP-Bang. Veterans also completed questionnaires assessing overall health, pain, depression, PTSD, and psychosocial functioning. RESULTS: 1,153 veterans were included in the present analyses (Mean age = 58.81; 21.84% female). Compared to non-VA healthcare users, veterans receiving care at the VA were more likely to have been diagnosed with OSA (p < .001) and report receiving treatment for OSA (p = .005). Compared to veterans at low risk for OSA, veterans at elevated risk reported higher levels of pain (p = .001), depression (p = .02), and poorer psychosocial functioning (p < .001). CONCLUSIONS: OSA diagnoses appear to be more common among VA healthcare users. Findings suggest that OSA remains underdiagnosed and associated with important physical and mental health consequences. Additional screening for OSA, especially among non-VA clinics, is warranted.
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Guerra del Golfo , Apnea Obstructiva del Sueño , Veteranos , Humanos , Femenino , Masculino , Persona de Mediana Edad , Veteranos/estadística & datos numéricos , Estados Unidos/epidemiología , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/terapia , Aceptación de la Atención de Salud/estadística & datos numéricos , Prevalencia , United States Department of Veterans Affairs/estadística & datos numéricos , Anciano , Adulto , Encuestas y Cuestionarios , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/terapia , Depresión/epidemiología , Depresión/terapiaRESUMEN
Gulf War Illness (GWI) is a major health problem for approximately 250,000 Gulf War (GW) veterans, but the etiology of GWI is unclear. We hypothesized that mitochondrial dysfunction is an important contributor to GWI, based on the similarity of some GWI symptoms to those occurring in some mitochondrial diseases; the plausibility that certain pollutants to which GW veterans were exposed affect mitochondria; mitochondrial effects observed in studies in laboratory models of GWI; and previous evidence of mitochondrial outcomes in studies in GW veterans. A primary role of mitochondria is generation of energy via oxidative phosphorylation. However, direct assessment of mitochondrial respiration, reflecting oxidative phosphorylation, has not been carried out in veterans with GWI. In this case-control observational study, we tested multiple measures of mitochondrial function and integrity in a cohort of 114 GW veterans, 80 with and 34 without GWI as assessed by the Kansas definition. In circulating white blood cells, we analyzed multiple measures of mitochondrial respiration and extracellular acidification, a proxy for non-aerobic energy generation; mitochondrial DNA (mtDNA) copy number; mtDNA damage; and nuclear DNA damage. We also collected detailed survey data on demographics; deployment; self-reported exposure to pesticides, pyridostigmine bromide, and chemical and biological warfare agents; and current biometrics, health and activity levels. We observed a 9% increase in mtDNA content in blood in veterans with GWI, but did not detect differences in DNA damage. Basal and ATP-linked oxygen consumption were respectively 42% and 47% higher in veterans without GWI, after adjustment for mtDNA amount. We did not find evidence for a compensatory increase in anaerobic energy generation: extracellular acidification was also lower in GWI (12% lower at baseline). A subset of 27 and 26 veterans returned for second and third visits, allowing us to measure stability of mitochondrial parameters over time. mtDNA CN, mtDNA damage, ATP-linked OCR, and spare respiratory capacity were moderately replicable over time, with intraclass correlation coefficients of 0.43, 0.44, 0.50, and 0.57, respectively. Other measures showed higher visit-to-visit variability. Many measurements showed lower replicability over time among veterans with GWI compared to veterans without GWI. Finally, we found a strong association between recalled exposure to pesticides, pyridostigmine bromide, and chemical and biological warfare agents and GWI (p < 0.01, p < 0.01, and p < 0.0001, respectively). Our results demonstrate decreased mitochondrial respiratory function as well as decreased glycolytic activity, both of which are consistent with decreased energy availability, in peripheral blood mononuclear cells in veterans with GWI.
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Síndrome del Golfo Pérsico , Plaguicidas , Veteranos , Humanos , Adenosina Trifosfato , Armas Biológicas , ADN Mitocondrial , Metabolismo Energético , Guerra del Golfo , Leucocitos Mononucleares , Bromuro de Piridostigmina , Estudios de Casos y ControlesRESUMEN
BACKGROUND: Since 1997, research on Gulf War illness (GWI) has predominantly used 3 case definitions-the original Research definition, the CDC definition, and modifications of the Kansas definition-but they have not been compared against an objective standard. METHODS: All 3 case definitions were measured in the U.S. Military Health Survey by a computer-assisted telephone interview in a random sample (n = 6,497) of the 1991 deployed U.S. military force. The interview asked whether participants had heard nerve agent alarms during the conflict. A random subsample (n = 1,698) provided DNA for genotyping the PON1 Q192R polymorphism. RESULTS: The CDC and the Modified Kansas definition without exclusions were satisfied by 41.7% and 39.0% of the deployed force, respectively, and were highly overlapping. The Research definition, a subset of the others, was satisfied by 13.6%. The majority of veterans meeting CDC and Modified Kansas endorsed fewer and milder symptoms; whereas, those meeting Research endorsed more symptoms of greater severity. The group meeting Research was more highly enriched with the PON1 192R risk allele than those meeting CDC and Modified Kansas, and Research had twice the power to detect the previously described gene-environment interaction between hearing alarms and RR homozygosity (adjusted relative excess risk due to interaction [aRERI] = 7.69; 95% CI 2.71-19.13) than CDC (aRERI = 2.92; 95% CI 0.96-6.38) or Modified Kansas without exclusions (aRERI = 3.84; 95% CI 1.30-8.52) or with exclusions (aRERI = 3.42; 95% CI 1.20-7.56). The lower power of CDC and Modified Kansas relative to Research was due to greater false-positive disease misclassification from lower diagnostic specificity. CONCLUSIONS: The original Research case definition had greater statistical power to detect a genetic predisposition to GWI. Its greater specificity favors its use in hypothesis-driven research; whereas, the greater sensitivity of the others favor their use in clinical screening for application of future diagnostic biomarkers and clinical care.
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Personal Militar , Síndrome del Golfo Pérsico , Veteranos , Humanos , Síndrome del Golfo Pérsico/diagnóstico , Síndrome del Golfo Pérsico/genética , Encuestas y Cuestionarios , Encuestas Epidemiológicas , Guerra del Golfo , ArildialquilfosfatasaRESUMEN
Medically unexplained syndromes (MUS), also termed persistent physical symptoms, are both prevalent and disabling. Yet treatments for MUS are marked by high rates of patient dissatisfaction, as well as disagreement between patients and providers on the management of persistent physical symptoms. A better understanding of patient-generated goals could increase collaborative goal setting and promote person-centered care, a critical component of MUS treatment; yet research in this area is lacking. This paper aimed to develop a typology of treatment and life goals among Gulf War veterans with a medically unexplained syndrome (Gulf War Illness). We examined participants' responses to open-ended questions about treatment and life goals using Braun and Clarke's thematic analysis methodology. Results showed that treatment goals could be categorized into four overarching themes: 1) Get better/healthier, 2) Improve quality of life, 3) Improve or seek additional treatment, and 4) Don't know/Don't have any. Life goals were categorized into six overarching themes: 1) Live a fulfilling life, 2) Live a happy life, 3) Live a healthy life, 4) Be productive/financially successful, 5) Manage GWI, and 6) Don't know/Don't have any. Treatment goals were largely focused on getting better/healthier (e.g., improving symptoms), whereas life goals focused on living a fulfilling life. Implications for the treatment of Gulf War Illness and patient-provider communication are discussed. ClinicalTrials.gov Identifier: NCT02161133.
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Síndrome del Golfo Pérsico , Veteranos , Humanos , Objetivos , Guerra del Golfo , Síndrome del Golfo Pérsico/terapia , Síndrome del Golfo Pérsico/diagnóstico , Calidad de VidaRESUMEN
BACKGROUND: During deployment, veterans of the 1991 Gulf War (GW) were exposed to multiple war-related toxicants. Roughly a third of these veterans continue to exhibit neurotoxicant induced symptoms of Gulf War Illness (GWI), a multi-faceted condition that includes fatigue, pain and cognitive decrements. When studied empirically, both deployed veterans with exposures and those who meet the criteria for GWI are more likely to show deficits in the area of neuropsychological functioning. Although studies have shown cognitive impairments in small sample sizes, it is necessary to revisit these findings with larger samples and newer cohorts to see if other areas of deficit emerge with more power to detect such differences. A group of researchers and clinicians with expertise in the area of GWI have identified common data elements (CDE) for use in research samples to compare data sets. At the same time, a subgroup of researchers created a new repository to share these cognitive data and biospecimens within the GWI research community. METHODS: The present study aimed to compare cognitive measures of attention, executive functioning, and verbal memory in a large sample of GWI cases and healthy GW veteran controls using neuropsychological tests recommended in the CDEs. We additionally subdivided samples based on the specific neurotoxicant exposures related to cognitive deficits and compared exposed versus non-exposed veterans regardless of case criteria status. The total sample utilized cognitive testing outcomes from the newly collated Boston, Biorepository, Recruitment, and Integrative Network (BBRAIN) for GWI. RESULTS: Participants included 411 GW veterans, 312 GWI (cases) and 99 healthy veterans (controls). Veterans with GWI showed significantly poorer attention, executive functioning, learning, and short-and-long term verbal memory than those without GWI. Further, GW veterans with exposures to acetylcholinesterase inhibiting pesticides and nerve gas agents, had worse performance on executive function tasks. Veterans with exposure to oil well fires had worse performance on verbal memory and those with pyridostigmine bromide anti-nerve gas pill exposures had better verbal memory and worse performance on an attention task compared to unexposed veterans. CONCLUSIONS: This study replicates prior results regarding the utility of the currently recommended CDEs in determining impairments in cognitive functioning in veterans with GWI in a new widely-available repository cohort and provides further evidence of cognitive decrements in GW veterans related to war-related neurotoxicant exposures.
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Síndrome del Golfo Pérsico , Veteranos , Humanos , Síndrome del Golfo Pérsico/inducido químicamente , Síndrome del Golfo Pérsico/epidemiología , Síndrome del Golfo Pérsico/psicología , Guerra del Golfo , Boston/epidemiología , Acetilcolinesterasa , CogniciónRESUMEN
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.
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Enfermedades Cardiovasculares , Diabetes Mellitus , Hiperlipidemias , Hipertensión , Síndrome del Golfo Pérsico , Veteranos , Humanos , Síndrome del Golfo Pérsico/epidemiología , Hiperlipidemias/epidemiología , Guerra del Golfo , Diabetes Mellitus/epidemiología , Encuestas y Cuestionarios , Hipertensión/epidemiologíaRESUMEN
The Kuwaiti oil fire during the first Gulf War resulted in the formation of approximately 300 "oil lakes" of varying sizes that covered over 110 km2 of the desert land. This threatens the fragile desert ecosystems and human health. Following the award of over US$2 billion to the State of Kuwait by the United Nations, large-scale remediation of the oil-contaminated soils has now been on the agenda. However, how to implement the remediation program in a cost-effective way represents a major challenge. In this study, cost-effective remediation strategies were developed based on field and laboratory investigations in a typical oil lake area. Overall, most of the lighter petroleum hydrocarbons (PHCs) were lost due to evaporation. Long-chain aliphatic PHCs dominated the PHCs in the investigated oil lake area. This has implications for developing remediation strategies. Toxicity assessment results showed that the majority of soils pose a low environmental risk with a hazard index <1. Therefore, intensive treatment of these PHCs may not be necessary for these soils. Although active treatment methods are needed to remove the contaminants as soon as practical for the relatively small areas of high contamination, more cost-effective passive methods should be considered to minimize the remedial costs for the larger area of the non-hotspot areas. Given the extremely low risk in terms of groundwater contamination by the contaminated soils, it may not be necessary to remove the soils from the contaminated sites. A low-cost capping method should be sufficient to minimize human exposure to the PHC-contaminated soils.
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Restauración y Remediación Ambiental , Petróleo , Contaminantes del Suelo , Humanos , Kuwait , Guerra del Golfo , Ecosistema , Análisis Costo-Beneficio , Contaminantes del Suelo/análisis , Hidrocarburos/análisis , Suelo , Biodegradación AmbientalRESUMEN
Gulf War Illness (GWI) collectively describes the multitude of central and peripheral disturbances affecting soldiers who served in the 1990-1991 Gulf War. While the mechanisms responsible for GWI remain elusive, the prophylactic use of the reversible acetylcholinesterase inhibitor, pyridostigmine bromide (PB), and war-related stress have been identified as chief factors in GWI pathology. Post-deployment stress is a common challenge faced by veterans, and aberrant cholinergic and/or immune responses to these psychological stressors may play an important role in GWI pathology, especially the cognitive impairments experienced by many GWI patients. Therefore, the current study investigated if an immobilization stress challenge would produce abnormal responses in PB-treated rats three months later. Results indicate that hippocampal cholinergic responses to an immobilization stress challenge are impaired three months after PB administration. We also assessed if an immune or stress challenge reveals deficits in PB-treated animals during hippocampal-dependent learning and memory tasks at this delayed timepoint. Novel object recognition (NOR) testing paired with either acute saline or lipopolysaccharide (LPS, 30 µg/kg, i.p.), as well as Morris water maze (MWM) testing was conducted approximately three months after PB administration and/or repeated restraint stress. Rats with a history of PB treatment exhibited 24-hour hippocampal-dependent memory deficits when challenged with LPS, but not saline, in the NOR task. Similarly, in the same cohort, PB-treated rats showed 24-hour memory deficits in the MWM task. Ultimately, these studies highlight the long-term effects of PB treatment on hippocampal function and provide insight into the progressive cognitive deficits observed in veterans with GWI.