{ "condition": "Gulf War Illness – Gulf War Illness (GWI)", "key": "gulf-war-illness", "last_updated": "2026-07-09T08:04:02.146379Z", "count": 75, "source": "PubMed (NCBI)", "studies": [ { "pmid": "42347851", "title": "The comparative ameliorating effects of an amorphous formula of curcumin and α-glycosyl isoquercitrin on hippocampal dysfunction in a rat gulf war illness model.", "pub_date": "2026-06-25", "journal": "Metabolic brain disease", "authors": "Tang, Qian, Shobudani, Momoka, Sakamaki, Yuri, Ebizuka, Yuri et al.", "abstract": "Brain dysfunction is a primary symptom of Gulf War illness (GWI). The present study investigated the effects of an amorphous formula of curcumin (CUR) and α-glycosyl isoquercitrin (AGIQ) on neurobehaviors and adult neurogenesis and following synaptic plasticity of produced neurons in the hippocampal dentate gyrus (DG) in a rat GWI model. Ten-week-old rats received GWI-related chemicals and restraint stress for 28 days; thereafter, animals were fed either a diet without supplement or mixed with 0.1% CUR or 0.5% AGIQ for 126 days. GWI treatment adversely affected behavioral endpoints, including novel object recognition, sucrose preference, novelty-suppressed feeding, and contextual fear conditioning. CUR ameliorated all these effects, while AGIQ caused anxiety-like behavior and improved fear extinction learning. GWI treatment downregulated NRF2-KEAP1 pathway-related genes in the DG; both phytochemicals reversed most of these changes. GWI treatment increased CD68", "url": "https://pubmed.ncbi.nlm.nih.gov/42347851/" }, { "pmid": "42328091", "title": "\"Treat us Like Human Beings\": Messages and Recommendations to U.S. Policymakers and Veterans Health Administration Providers from a Qualitative Inquiry Into the Health Experiences of Gulf War Veterans With Gulf War Illness.", "pub_date": "2026-06-22", "journal": "Journal of patient experience", "authors": "Montague, Kara A, Lafferty, Megan, Graham, Michael, Nugent, Shannon M", "abstract": "Gulf War Illness (GWI) affects many U.S. Veterans of the 1990-1991 Persian Gulf War (GWVs), yet recognition of the condition and effective treatments remain limited. GWVs with GWI describe feeling dismissed by institutions tasked with their benefits and healthcare, fueling mistrust and disengagement. This qualitative study explored the messages GWVs with GWI wished to convey to the Department of Veterans Affairs (VA) providers and U.S. policymakers. We conducted semi-structured interviews (2019-2022) with a national sample of 39 GWVs with GWI. Veterans emphasized persistent challenges in transitioning to VA care, navigating complex disability claims, and obtaining recognition of GWI as a chronic, service-connected illness. Participants perceived inequities in recognition, benefits, and other support compared to other service eras, and mistrust in compensation and pension processes. Finally, central to these GWI narratives was a desire to be heard, acknowledged, and validated. These findings underscore the importance of Veteran-informed policies, provider education, and empathetic and cooperative dialogue in restoring trust and improving care for GWI.", "url": "https://pubmed.ncbi.nlm.nih.gov/42328091/" }, { "pmid": "42296096", "title": "Association between deployment and Gulf War Illness and adverse COVID outcomes in a nationwide cohort of 1990-1991 Gulf Era war veterans in the VA's Million Veteran Program.", "pub_date": "2026-06-15", "journal": "PloS one", "authors": "White, Donna L, NonoDjotsa, Alice B S, Ahmed, Sarah T, Boyle, Stephen H et al.", "abstract": "U.S. military veterans deployed to the Persian Gulf to serve in the 1990-1991 Gulf War (GWVs) have expressed concerns about potential increased risk of experiencing adverse COVID-related health outcomes given broad near-unique exposure to multiple diverse toxic agents during deployment and ongoing ~30% prevalence of Gulf War Illness (GWI+), a chronic, medically unexplained multi-symptom disorder associated with inflammation and immune dysregulation. We conducted a retrospective study in the largest nationwide research cohort of 1990-1991Gulf War era veterans (GWEVs) enrolled in the VA's nationwide Million Veteran Program (MVP) to interrogate: 1) if deployed GWVs had increased risk for testing positive for novel SARS-CoV-2 infection (COVID+), COVID-related hospitalization, ICU admission, or death in 2020 (pre-vaccine period); and 2) if deployed GWVs with GWI+ had particularly increased susceptibility. COVID outcomes ascertained using VA's COVID Data Resource; GWI+ determined using CDC severe criteria in surveyed GWV subcohort. Our overall GWEV cohort (N = 136,868) had mean age 60.7 years, with 84% male, 27% African-American, and 22% deployed; n = 26,141 COVID-tested in 2020. COVID test-positivity (COVID+) was slightly higher in deployed GWVs (18.8% vs. 17.2% in non-deployed GWEVs, p = 0.005). In multivariable logistic models, there were neither strong nor significant associations between deployment and testing COVID+, COVID-related hospitalization or ICU admission (adjusted [adj] ORs ranged from 0.90-1.06, all p-values >0.05), nor significant differences in COVID-related mortality. Preliminary analysis in our pre-pandemic surveyed deployed GWV subcohort (N = 1,643 COVID-tested, 39% GWI+, 18.4% testing-COVID+, 10.6% COVID+ hospitalized) suggested GWI+ potentially associated with significantly increased COVID-hospitalization risk (adjOR=2.21, 95%CI: 1.02-4.81, p = 0.04); though no significant excess was observed for COVID-related ICU admission or mortality. Our findings demonstrated that overall deployment to serve in the 1990-1991 Gulf War was not associated with increased COVID-related health risks among Gulf War era veterans using VA healthcare system in early pre-vaccine pandemic era. Preliminary findings suggesting association between Gulf War Illness and potential increased COVID-related hospitalization risk among deployed Gulf War veterans in the early pandemic era warrants replication and ongoing evaluation to assess if it persists in the era of COVID vaccination, oral anti-COVID medications and new viral variants.", "url": "https://pubmed.ncbi.nlm.nih.gov/42296096/" }, { "pmid": "42277823", "title": "Observational and genetically-informed characterization of Gulf War Illness symptoms in 1990-1991 Gulf War deployed Veterans and non-deployed Gulf War Era Veterans.", "pub_date": "2026-06-12", "journal": "Environmental health : a global access science source", "authors": "He, Jun, Pathak, Gita A, Cabrera-Mendoza, Brenda, Qiu, Dan et al.", "abstract": "Gulf War Illness (GWI) has been identified in more than 20% of Veterans following military service in the 1990-1991 Gulf War (GW). Unfortunately, after several decades, GWI pathogenesis remains unclear and the patterns of GWI symptom co-occurrence are still poorly understood. This population-based case-control study included 34,179 (16% females; 34% GW deployed; mean age 61 years) Veterans enrolled in the Million Veteran Program (MVP) who were active-duty military personnel in 1990-1991. We analyzed 14 GWI symptoms in GW-deployed and non-deployed GW-Era Veterans. Multivariable generalized linear models were used to estimate GWI symptom associations with demographic factors and deployment status. Correlation, factor, and network analyses were performed to examine the underlying structure of GWI symptoms. In addition, polygenic risk score and one-sample Mendelian randomization analyses were conducted to evaluate the genetically inferred effects of health-related traits on symptom factors. Among 14 GWI symptoms, joint pain had the highest prevalence in both GW deployed (86%) and non-deployed GW-Era Veterans (79%). The median age of symptom onset ranged from 38 to 46 years among deployed Veterans and from 45 to 54 years among non-deployed Veterans. Factor analysis identified a five-factor latent structure as the best-fit model for GWI symptoms, and latent class analysis classified Veterans into seven symptom classes. The network of GWI symptoms showed that fatigue had the largest closeness and betweenness and had more edges in deployed Veterans. Younger age, female sex, non-European descent, lower educational attainment, enlisted rank, and GW deployment, as well as multiple GW-related exposures in deployed Veterans, were associated with increased GWI symptom burden. Genetic liability to multiple health-related outcomes, including type 2 diabetes (T2D) and posttraumatic stress disorder (PTSD), showed putative causal effects on GWI-symptom factors, with the T2D effect being larger in deployed Veterans and the PTSD effect being larger in non-deployed Veterans. The present findings demonstrate differences in symptom onset between deployed and non-deployed GW Veterans. They also reinforce the importance of symptom clusters of relevance to GWI, associations between deployment-specific exposures and symptom burden, and different genetic linkages underlying symptoms for deployed and non-deployed groups. Not applicable.", "url": "https://pubmed.ncbi.nlm.nih.gov/42277823/" }, { "pmid": "42222193", "title": "Mitochondrial Bioenergetic Approach to Restore Veteran Vitality: A Feasibility Pilot.", "pub_date": "2026-06-01", "journal": "Integrative medicine (Encinitas, Calif.)", "authors": "Osinubi, Omowunmi, Greer, Steven, McManus, Pauline, Carlson, Carrie J et al.", "abstract": "No abstract available.", "url": "https://pubmed.ncbi.nlm.nih.gov/42222193/" }, { "pmid": "42033863", "title": "Toxic exposure and rates of suicidal thoughts and behaviors among U.S. military veterans.", "pub_date": "2026-04-26", "journal": "Psychiatry research", "authors": "Bourassa, Kyle J, Stephenson, Mallory, Dennis, Paul A, Patel, Tapan A et al.", "abstract": "Exposure to toxic substances has been linked to poorer mental health among U.S. military veterans broadly, but less is known about specific psychiatric outcomes, such as suicidal thoughts and behaviors (STBs). In the current observational cohort study, we investigated toxic exposure and STBs using data from 248,926 veterans enrolled in the Million Veteran Program (MVP). Exposures to nine toxins (Agent Orange, chemical/biological weapons, anthrax vaccine, solvents/fuels, petroleum combustion products, lead, other metals, pesticides, and open-air burn pits) were assessed using self-report, and subsequent health records were used to assess STBs. Veterans with more toxic exposures were more likely to have STBs (OR = 1.17, 95% CI [1.16, 1.18], p < .001). In secondary analyses, we found associations were comparable (1.11 ≤ ORs ≤ 1.19) across major service cohorts in the MVP (pre-Vietnam, Vietnam, post-Vietnam, Gulf War, and post-9/11 eras). We also present rates and associations for specific toxic exposures, associations for specific categories of STBs, and show that PTSD and depressive symptoms accounted for the association between toxic exposure and STBs. Our results suggest that veterans who report more toxic exposure are also more likely to have STBs, and this association can be interpreted as a broader association between toxic exposure and poorer mental health. Future research is needed to determine whether toxic exposure might interact with genetic vulnerability to predict STBs for veterans, as well as how toxic exposure might result in increased risk for STBs.", "url": "https://pubmed.ncbi.nlm.nih.gov/42033863/" }, { "pmid": "41993916", "title": "Multi-omic analysis reveals brain-blood concordance and persistent neuroimmune reprogramming with stress and toxicant exposure in a mouse model of Gulf War Illness.", "pub_date": "2026-04-17", "journal": "Brain, behavior, & immunity - health", "authors": "Sasaki, A, Kelly, K A, Michalovicz, L T, Ashbrook, D G et al.", "abstract": "Gulf War Illness (GWI) is a chronic neuroimmune condition affecting veterans of the 1990-91 Gulf War. Current treatments primarily target symptom relief, and the biological mechanisms underlying GWI remain poorly understood. Using a validated mouse model of Gulf War Illness (GWI) combining corticosterone (CORT) and diisopropyl fluorophosphate (DFP) exposure to induce stress- and toxicant-related neuroimmune priming, we examined how prior exposure alters molecular responses to a subsequent immune challenge. Male mice were exposed to CORT and DFP with repeated intermittent CORT, followed by lipopolysaccharide (LPS) or saline to assess transcriptional and epigenetic changes in brain and blood. We analysed transcript abundance, chromatin accessibility, and DNA methylation in the hippocampus, frontal cortex, and blood at 6 h, 12 h and 24hrs after LPS challenge (3-4 mice per group). We identified widespread transcriptional changes and dynamic chromatin accessibility following LPS exposure, with DNA methylation modifications that persisted in the hippocampus and blood. Thirty-three genes, including", "url": "https://pubmed.ncbi.nlm.nih.gov/41993916/" }, { "pmid": "41972479", "title": "Cracking the Code: Which Ocular Symptoms Predict Dry Eye Signs? Insights From a Large International Sicca Registry.", "pub_date": "2026-04-13", "journal": "Arthritis care & research", "authors": "Donthineni, Pragnya R, Shields, Chloe, Muralidhar, Rohit, Bhatt, Shreya et al.", "abstract": "The study aimed to identify symptom-based predictors of dry eye disease (DED) signs in the Sjögren's International Collaborative Clinical Alliance (SICCA) cohort. We performed a retrospective analysis examining 16 ocular symptoms (most graded 0-4) and artificial tear (AT) use (graded 0-3) as predictors of DED signs (abnormal ocular surface staining [OSS] and Schirmer's test [ST], graded yes/no). Symptoms included descriptors of spontaneous and evoked pain, visual complaints, and other metrics (eg, redness). Logistic regressions were used for univariable and multivariable analyses, with OSS and ST as outcome variables. Hierarchical analyses were performed to identify symptom-based clusters. The mean age of the population (n = 3,514) was 53 ± 13 years; 91% were female, 54% were White, and 44% met 2016 criteria for Sjögren disease. On multivariable analysis, OSS was positively related to AT use (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.36-1.67), eye redness (OR 1.17, 95% CI 1.08-1.26), and blurred vision (OR 1.11, 95% CI 1.02-1.20). Similarly, eyes that felt dry, AT use, and blurred vision were positively related to ST. Cluster analysis revealed three groups with varied symptom burden (low, mild-moderate, and high). The mild-moderate cluster had higher frequencies of abnormal ocular signs and positive serologic test results (anti-SSA/Ro antibody, elevated IgG level) compared to the high symptom burden cluster. AT use and blurred vision were stronger indicators of ocular surface and tear film abnormalities than pain symptoms, and their presence merits an ophthalmology referral. Symptom-based clustering revealed varied symptom burden groups, likely driven by underlying neurotrophic and neuropathic mechanisms, highlighting heterogeneity within sicca presentations and the need to develop phenotype-based targeted therapies.", "url": "https://pubmed.ncbi.nlm.nih.gov/41972479/" }, { "pmid": "41961384", "title": "Spermidine Attenuates Neuroimmune Dysfunction in Gulf War Illness via Modulation of the Gut- Brain Axis.", "pub_date": "2026-04-10", "journal": "Molecular neurobiology", "authors": "Trivedi, Ayushi, Roy, Subhajit, More, Madhura, Bose, Dipro et al.", "abstract": "Gulf War illness (GWI) affects nearly one-third of US veterans deployed during the 1990-1991 Gulf War (GW) and is characterized by chronic fatigue, neuroinflammation, and gut dysbiosis. Through comprehensive fecal metabolomics sequencing, our lab previously reported the depletion of beneficial metabolites including spermidine in the preclinical GWI mouse model. Spermidine is an endogenously synthesized polyamine known for its anti-inflammatory and mucosal barrier protective effects in various pathological diseases. Given its established role in mitigating intestinal inflammation and maintaining homeostasis, this study investigated the therapeutic potential of spermidine in a persistent (22 weeks) GWI mouse model, with a specific focus on gut-brain axis regulation. Our results demonstrated that spermidine effectively restored both microbial richness and diversity by selectively enriching beneficial bacterial taxa and suppressing growth of opportunistic pathogens, which are otherwise dysregulated following exposure to GW chemicals. Spermidine treatment also improved gut epithelial barrier integrity and reduced epithelial release of high-mobility group box 1 (HMGB1) into systemic circulation. Recent studies on GWI have implicated a critical role of gut-derived damage-associated molecular patterns (DAMPs), particularly HMGB1 in mediating neuroinflammation. Our findings indicate that systemic levels of HMGB1 critically influence the extent of blood-brain barrier (BBB) disruption and subsequent microglial activation. Mechanistically, spermidine activated intestinal aryl hydrocarbon receptor (AhR)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling, which played a role in limiting intestinal HMGB1 release and suppressing downstream receptor for advanced glycation end-product (RAGE)-mediated microglial activation in the brain. In vitro results indicate spermidine promoted AhR/Nrf2 nuclear translocation which reduced LPS-induced HMGB1 release from primary intestinal epithelial cells (IECs), effects abrogated by AhR inhibition. Additionally, we observed that HMGB1 directly induces microglial activation via RAGE receptors in immortalized microglial (IMG) cell lines in a dose-dependent manner. These results demonstrate that spermidine decreases neuroinflammation by modulating gut-brain axis pathophysiology associated with GWI. Together, this study demonstrates the therapeutic role of spermidine in ameliorating systemic and neurological disturbances in GWI.", "url": "https://pubmed.ncbi.nlm.nih.gov/41961384/" }, { "pmid": "41896945", "title": "Genomic interplay between deployment exposures and Gulf War illness in Million Veteran Program participants.", "pub_date": "2026-03-28", "journal": "Human genomics", "authors": "Qiu, Dan, Cabrera-Mendoza, Brenda, He, Jun, Steele, Lea et al.", "abstract": "Veterans of the 1990–1991 Gulf War (GW) experienced an elevated burden of chronic health conditions, most notably Gulf War Illness (GWI). While the disease etiology remains unclear, it is hypothesized that both genetic susceptibility and deployment exposures contribute to GWI risk. We investigated 6,882 GW-deployed Veterans, assessing genetic and epigenetic interactions with GW exposures (ground combat, insect baits, oil well smoke exposure, pyridostigmine bromide pills, biological/chemical warfare agents, and pesticides). We observed nominal evidence of a genome-wide gene–environment interaction variance component (0.38 ± 0.22) related to biological/chemical warfare-agent exposure and identified three loci showing genome-wide significant interactions (p < 5 × 10− 8; rs78441512, rs145790544, and rs117997207). Also, type-2 diabetes polygenic risk association with GWI is reduced in Veterans exposed to biological/chemical warfare agents, pesticides, and oil well fire smoke during GW deployment. An exploratory computational drug-repurposing analysis highlighted clebopride, rifampicin, and fisetin as compounds potentially targeting GWI-associated molecular pathways. Our GWI epigenome-wide association study identified five sites showing epigenetic interaction with four GW exposures: ground combat, biological/chemical warfare agents, pyridostigmine bromide pill use, and pesticide use. In conclusion, our study demonstrates that both genetic and epigenetic factors interact with GW military exposures to influence GWI vulnerability, highlighting potential druggable pathways to develop novel therapeutic interventions.", "url": "https://pubmed.ncbi.nlm.nih.gov/41896945/" }, { "pmid": "41860162", "title": "Deployment of an Activity Monitoring Program to Complement a Clinical Intervention for Veterans With Gulf War Illness: Qualitative Study.", "pub_date": "2026-03-20", "journal": "JMIR human factors", "authors": "Mak, Selene S, McManus, Pauline, Greer, Steven, Haws, Kari et al.", "abstract": "Many veterans who served in the Gulf experience Gulf War Illness (GWI), a chronic multisymptom condition associated with fatigue, pain, gastrointestinal problems and respiratory issues, mood/cognitive issues, and sleep difficulties. These symptoms contribute to decreased function, increased mental health needs, and poor quality of life. The Veterans Affairs War Related Illness and Injury Study Center in New Jersey developed a 26-week virtual health coaching intervention to support symptom management for veterans with GWI. In 2023, a consumer-grade smartwatch was added as part of an activity monitoring program to complement this program. The purpose of this project was to assess the feasibility and acceptability of including a smartwatch-based activity monitoring component to complement a virtual health coaching program for veterans with GWI. Twenty-four veterans enrolled in the health coaching program were invited to participate in the activity monitoring component. Participants attended a virtual orientation to set up the smartwatch, and verbal consent to share data through a Health Insurance Portability and Accountability Act (HIPAA)-compliant platform was obtained. Program feasibility was assessed by evaluating wear-time percentage and duration of use. Acceptability was assessed using two items from a monthly survey and through a midprogram semistructured interview. Quantitative data were summarized descriptively, and qualitative data were analyzed using a coding scheme adapted from Sekhon et al's Theoretical Framework for Acceptability (TFA). Twenty veterans agreed to participate in the program (mean age 49 years; 7/20, 35% female; 19/20, 94% non-Hispanic White; 11/20, 55% first-time smartwatch users). Twelve participants (60%) wore the watch for the full 26 weeks. Among participants who completed 26 weeks, median daily wear-time completeness exceeded 80% for 25 weeks. Most participants (12/20, 60%) reported that wearing the smartwatch helped them achieve their wellness goals, and the majority (16/20, 80%) said they would recommend using the smartwatch for activity monitoring to other veterans. Qualitative findings supported acceptability across TFA domains. One adverse event was reported (minor skin irritation that resolved after changing the smartwatch band to a hypoallergenic watch band). Within this clinical program, pairing a smartwatch with virtual health coaching for veterans with GWI was feasible and acceptable. Activity monitoring integrated into an existing intervention may support symptom self-management and augment patient education and engagement. As no prior activity monitoring programs specific to veterans with GWI have been described, these findings could inform future program development and implementation within this population.", "url": "https://pubmed.ncbi.nlm.nih.gov/41860162/" }, { "pmid": "41843558", "title": "Computational modeling-directed combination treatment with etanercept and mifepristone mitigates neuroinflammation in a mouse model of Gulf War Illness.", "pub_date": "2026-03-18", "journal": "PloS one", "authors": "Kelly, Kimberly A, Felton, Christopher M, Billig, Brenda K, Yilmaz, Ali A et al.", "abstract": "Gulf War Illness is a chronic multi-symptom disorder experienced by over 30% of veterans from the 1990-1991 Gulf War and is increasingly recognized to be driven by underlying persistent neuroinflammation resulting from chemical and physiological exposures experienced during deployment. Despite significant advances in identifying Gulf War-relevant exposures and underlying pathobiology, effective treatment strategies for Gulf War Illness are still largely lacking. Many studies that have evaluated potential therapies for Gulf War Illness have primarily focused on a single treatment. However, through a mechanistically informed computational evaluation of blood biomarkers and gene expression in veterans with Gulf War Illness, we identified that a combination of anti-inflammatory and anti-glucocorticoid treatment may prove effective in treating Gulf War Illness. Here, we have evaluated combined treatment with the anti-TNFα drug, etanercept, and anti-glucocorticoid, mifepristone, in an established long-term mouse model of Gulf War Illness of combined physiological stress and nerve agent exposure. Supporting results from the computational modeling of this treatment, we found that this drug combination significantly alleviates the underlying neuroinflammation associated with Gulf War Illness. The fusion of computational and in vivo preclinical treatment evaluation may provide a highly useful and translationally relevant means by which to identify successful treatment paradigms for Gulf War Illness.", "url": "https://pubmed.ncbi.nlm.nih.gov/41843558/" }, { "pmid": "41830111", "title": "Illness perceptions and behavioural responses as mechanisms of change in problem-solving treatment for Veterans with Gulf War Illness.", "pub_date": "2026-03-14", "journal": "British journal of health psychology", "authors": "Lesnewich, Laura M, Winograd, Darren M, Lu, Shou-En, Quigley, Karen S et al.", "abstract": "Persistent 'medically unexplained' physical symptoms and syndromes (PPS), an umbrella term for symptom-based conditions with poorly understood pathophysiology and aetiology, disproportionately impact Gulf War Veterans. Behavioural interventions are efficacious and recommended as first-line treatments for PPS, but the mechanisms by which these interventions work remain unknown. This study sought to identify mechanisms of change that make problem-solving treatment (PST) efficacious for Veterans living with Gulf War Illness (GWI), a common form of PPS among Veterans who served in Operations Desert Shield/Storm. Veterans with GWI were randomized to receive either PST or an active control intervention. Analyses focused on the 135 Veterans who were randomized to the PST condition. Outcomes of interest included disability, depressive symptoms, and physical symptoms. Threatening and protective illness perceptions as well as maladaptive and adaptive behavioural responses to illness were analysed as mechanisms of change (i.e., mediators) of these outcomes over time in single-arm mediation models. All three outcomes were mediated by reduced threatening illness perceptions (p-values .032-.047) and reduced maladaptive behavioural responses (all-or-nothing and limiting responses; p-values .004-.007). Changes in protective illness perceptions and adaptive behavioural responses to illness were not significant mediators of PST outcomes. Consistent with the cognitive behavioural model of PPS and the Common-Sense Model of Self-Regulation, changes in negative illness perceptions and behavioural responses may act as mechanisms of change in PST for GWI.", "url": "https://pubmed.ncbi.nlm.nih.gov/41830111/" }, { "pmid": "41798890", "title": "Macrophage Immune-Competent Colon Assembloids for Functional Interrogation of Neuroinflammation-Induced Colonic Dysmotility.", "pub_date": "2026-03-09", "journal": "Gastro hep advances", "authors": "Collier, Claudia A, Ortega Sandoval, Karla I, Salikhova, Aelita, Rengarajan, Shrinarayanee et al.", "abstract": "Background and Aims: Functional gastrointestinal disorders affect ∼40% of the global population and are frequently characterized by colonic dysmotility. Symptomatic manifestations of colonic dysmotility significantly reduce quality of life in inflammatory bowel disease, diabetes, and Gulf War Illness. Current in vitro models lack the integration of functional physiology with immune and neuronal complexity required to establish causal links between neuroinflammation and dysmotility. Here, an immune-competent bioengineered colon assembloid is introduced that integrates multiple cell types of the external colonic wall, along with functional readouts of motility. Bioengineered colon assembloids were fabricated using immortalized smooth muscle cells, enteric neuronal progenitor cells, and macrophage immune cells embedded within collagen hydrogels. Assembloids were allowed to compact and mature, prior to inflammatory insult with pyridostigmine bromide or tumor necrosis factor-alpha. Within bioengineered colon assembloids, various inflammatory insults resulted in enteric neuroinflammation, cascading to changes in colonic motility. Key mechanisms of dysmotility following inflammatory insult within the bioengineered colon assembloids included impaired neuronal regeneration and aberrant smooth muscle remodeling. The bioengineered colon assembloid model mimicked diverse aspects of enteric neuroinflammation. Ultimately, the platform offers a physiologically relevant avenue to interrogate neuroimmune crosstalk and dissect mechanisms of colonic dysmotility, paving the way to new therapeutic strategies to improve colonic motility.", "url": "https://pubmed.ncbi.nlm.nih.gov/41798890/" }, { "pmid": "41774973", "title": "Tai Chi and wellness for Gulf War Illness: Combined analysis of in-person and remote randomized controlled trials.", "pub_date": "2026-03-03", "journal": "Journal of psychiatric research", "authors": "Polizzi, Craig P, Crow, Thomas M, Ting, Maria, Busser, Cameron et al.", "abstract": "Veterans with Gulf War Illness (GWI) experience a wide range of physical, neurological, cognitive, and mood complications that can lead to distressing psychological symptoms. Despite its debilitating impact on physical and psychological functioning, effective treatment options for GWI remain limited. Tai Chi, an ancient Chinese mind-body practice, may be efficacious in reducing GWI symptoms and associated mental health challenges. The present study combined data from two randomized controlled trials (RCTs) examining a Tai Chi group intervention relative to a Wellness comparison group intervention. Primary outcomes were GWI symptoms (health symptoms, pain interference, fatigue, and depressed mood), with secondary outcomes including anxiety, stress, sleep disturbances, mindfulness, health-related quality of life, and PTSD symptoms. We also evaluated whether treatment delivery modality (in-person versus remote) influenced outcomes. Participants were 114 veterans with GWI and chronic pain. They completed self-report measures at baseline, posttreatment, 3-month follow-up, and 9-month follow-up. Preliminary multilevel modeling indicated that treatment modality (in-person versus remote) did not significantly influence outcomes. Both Tai Chi and Wellness interventions were associated with improvements in health symptoms, pain interference, depression, anxiety, mindfulness, mental and physical health-related quality of life, and PTSD symptoms. Tai Chi and Wellness group interventions may demonstrate similar efficacy in improving GWI symptoms and mental health outcomes among veterans with GWI and chronic pain. These interventions can be delivered in-person and remotely with comparable therapeutic benefits, offering flexible and accessible treatment options for this underserved population.", "url": "https://pubmed.ncbi.nlm.nih.gov/41774973/" }, { "pmid": "41705454", "title": "Imaging of Ocular Surface Lesions Using Anterior Segment Optical Coherence Tomography.", "pub_date": "2026-02-18", "journal": "Clinical & experimental ophthalmology", "authors": "Li, Wendy J, Muthu, Pragat J, Galor, Anat, Karp, Carol L", "abstract": "Ocular surface lesions encompass a wide spectrum of entities ranging from benign degenerative lesions to non-invasive and invasive malignant tumours. Accurate clinical differentiation is essential to ensure timely management. In this manuscript, we describe a series of benign and malignant ocular surface lesions and their clinical and specific imaging findings on anterior segment optical coherence tomography (AS-OCT), highlighting the diagnostic utility of this non-invasive imaging modality. We characterise ocular surface squamous neoplasia, pterygia, Salzmann's nodular degeneration, conjunctival melanoma, primary acquired melanosis, conjunctival nevus, conjunctival lymphoma, benign reactive lymphoid hyperplasia and conjunctival amyloidosis. This series underscores the growing role of AS-OCT in supporting clinical assessment, guiding biopsy decisions and monitoring response to therapy in patients with ocular surface lesions. Its integration into routine practice offers a valuable, non-invasive supplement to slit-lamp biomicroscopy and histopathology.", "url": "https://pubmed.ncbi.nlm.nih.gov/41705454/" }, { "pmid": "41657838", "title": "Polycyclic aromatic hydrocarbon exposure in battlefield and beyond: Implications for environmental- and human health.", "pub_date": "2026-02-09", "journal": "Toxicology reports", "authors": "Hamilton, Markis' D, Chauhan, Ritu, Archibong, Anthony E, Ramesh, Aramandla", "abstract": "Polycyclic aromatic hydrocarbons (PAHs) are combustion pollutants that are released into the environment through natural events and anthropogenic activities. Exposures to PAHs occur in military personnel during garrison (non-combat) and active deployment (combat) environments. Exposures that occur at low levels during deployment could lead to health issues, post-deployment. A scoping review was conducted to address the pathways of exposure, and the adverse effects caused by PAHs in active-duty personnel and veterans. Out of 50,171 scientific publications screened from 5 databases, 296 studies were identified that focused on the relationship between exposure to PAHs from various point sources and debilitating health issues reported in veterans. The findings revealed that in combat conditions, PAHs are released into the environment through explosions caused by bombing, artillery fire, and missile attacks on military installations, petrochemical industries, oil well fires set by saboteurs, and burn pits used to incinerate ammunition waste and military base refuse. Significant exposure of troops to PAHs occurred during active combat in the Operation Desert Shield, Operation Desert Storm, and Operation Enduring Freedom campaigns launched against hostile forces. The PAH releases contaminated not only the affected service personnel and staff, but also the surrounding environment. The coastal environment, including its flora and fauna, were affected by oil tanker fires, petroleum storage tanks that caught fire during conflict and subsequent release of PAHs into the marine environment. The human health effects resulting from PAH exposures included severe lung-, kidney-, and reproductive dysfunctions, as well as an increased risk of cancer, mostly manifested in Veterans as part of the Gulf War Syndrome. The Exposome approach utilizing the omics-based biomarkers to characterize individual service member profile with wearable monitors (wrist bands and sensors) to characterize the external environment when combined with biomonitoring studies holds significant promise for treatment of troops during combat and post deployment.", "url": "https://pubmed.ncbi.nlm.nih.gov/41657838/" }, { "pmid": "41648243", "title": "Modeling Inflammation-Driven Colon Hypertrophy and Motility Changes in Gulf War Illness.", "pub_date": "2026-02-06", "journal": "bioRxiv : the preprint server for biology", "authors": "Anantha Krishnan, Ahilan, Raghavan, Shreya A, Holland, Maria A", "abstract": "Gastrointestinal (GI) symptoms are a prominent feature of Gulf War Illness (GWI). Animal models attribute them to pyridostigmine bromide (PB) exposure, which induces smooth muscle hypertrophy, neuroinflammation, and motility impairment. However, animal studies only provide static snapshots of disease progression and can only partially resolve how inflammatory, neuronal, and biomechanical processes interact dynamically over time. To address this gap, we developed a computational model that couples cytokine kinetics, macrophage activation, and an excitatory-inhibitory neuronal imbalance to predict smooth muscle hypertrophy and colonic motility changes in GWI. The model was calibrated using data from mice exposed to PB under acute (7-day exposure and measurement) and chronic (7-day exposure and 30-day measurement) conditions, reproducing measured cytokine IL-6 elevations, macrophage accumulation, circular muscle thickening, and shifts in excitatory and inhibitory gene expression. Simulations captured reduced excitatory stress, and sustained loss of inhibitory relaxation, consistent with organ-bath recordings. Sensitivity analyses identified macrophage persistence as a dominant regulator of chronic inhibitory dysfunction, whereas excitatory pathways exhibited relative robustness and recovery. Thus, our model provides a systems-level view of how acute PB-induced inflammation evolves into chronic dysmotility and establishes a first step towards a virtual platform for testing hypotheses and interventions translatable to neuroimmune GI disorders.", "url": "https://pubmed.ncbi.nlm.nih.gov/41648243/" }, { "pmid": "41619056", "title": "Gulf War Illness: Neurological Impacts, Pathophysiological Insights, and Therapeutic Prospects.", "pub_date": "2026-01-31", "journal": "Molecular neurobiology", "authors": "Mantilla, Fabian, Patel, Nidhi, Cheema, Amanpreet K, Parmar, Mayur S", "abstract": "Gulf War Illness (GWI) is a chronic, multi-system condition affecting a substantial proportion of veterans deployed during the 1990-1991 Gulf War. Neurological complications, including cognitive impairment, musculoskeletal pain, fatigue, depression, and migraine, represent a major clinical burden. Evidence implicates neuroinflammation, oxidative stress, mitochondrial dysfunction, and epigenetic dysregulation as central mechanisms, with emerging data suggesting early tauopathy and sex-specific immune responses. Neuroimaging studies reveal hippocampal atrophy, white matter disruptions, and increased translocator protein (TSPO) binding, while biomarker analyses identify elevated C-reactive protein (CRP), leptin, and matrix metalloproteinases. Genetic factors, such as HLA alleles, may modulate susceptibility. Animal models corroborate these findings, demonstrating hippocampal dysfunction, neurotransmitter imbalance, and neuroimmune activation following exposure to Gulf War-related chemicals. Therapeutic evidence supports cognitive behavioral therapy (CBT), exercise, and mindfulness-based interventions, with ongoing trials exploring vagus nerve stimulation, anti-inflammatory agents, and mitochondrial-targeted therapies. This review synthesizes current knowledge on GWI-related neurological dysfunction, highlights diagnostic and therapeutic advances, and underscores the need for biomarker-driven, sex-specific, and personalized approaches to improve outcomes for affected veterans.", "url": "https://pubmed.ncbi.nlm.nih.gov/41619056/" }, { "pmid": "41617203", "title": "Military Exposures Research: A State-of-the-Art Review.", "pub_date": "2026-01-31", "journal": "Military medicine", "authors": "Wright, Rachel T, Lindheimer, Jacob B, Christie, Israel C, Ramkissoon, Jaraad et al.", "abstract": "Military personnel encounter a wide range of environmental and occupational exposures during their service such as burn pit smoke, chemical warfare agents, depleted uranium, jet fuel, radiation, and pesticides. The field of military exposures research seeks to better understand the nature of these exposures and their effects on Veteran and service member health. This state-of-the-art review assesses the breadth and depth of published military exposures research so that stakeholders can identify trends and gaps in this growing field. An evidence mapping approach was used to perform a literature review of military exposures research published from 1962 to 2024. The search strategy was developed around exposed cohorts: groups of military personnel with a shared potential for exposure to toxic agents. Publications were included if they directly addressed exposures or related health outcomes in military cohorts. Publications were then further categorized by the type of research, and the results were analyzed to build a map of the current military exposures research landscape. Thirty-six exposed cohorts were identified in the literature which were then grouped based on the nature of the exposure event: Wars and Operations (4 cohorts), Occupational Exposures (5), Combat and Combat Training (2), Across Military (2), Ship Exposures (2), Defense Testing (2), Base/Garrison Exposures (9), Toxic Substance Clean-Up and Disposal (5), and Isolated Exposure Events (5). The search identified 2,321 publications that fit the review inclusion criteria. The exposed cohort with the highest number of publications was Gulf War (940, 40.5% of all publications) followed by Vietnam War (277, 11.9%), Post-9/11 Operations in Iraq and Afghanistan (191, 8.2%), Aircraft Mechanics and Ground Support (176, 7.6%), and Munition Emissions and Embedded Fragments (164, 7.1%). Each remaining cohort individually represented < 4% of the literature. Six cohorts appeared only in non-peer-reviewed reports. The type of research best represented was Epidemiology (34.0%) followed by Animal and In Vitro Models (18.8%), Sequelae and Management (17.1%), Reviews and Meta-Analyses (11.7%), Exposure Assessment (9.5%), Toxic Agent Sampling and Analysis (4.3%), and publications from the National Academy of Sciences, Engineering, and Medicine (4.6%). The volume of military exposures research has increased steadily since the early public reports of Gulf War Illness in 1994, with 50% of articles being published after 2008. Military exposures research published since 1962 has focused on cohorts from large, high-profile deployments, particularly the Gulf War. Underrepresented cohorts with potential exposures on bases or from military occupations present opportunities for future research. The lack of meaningful exposure assessment data that has been published also points to further research opportunities to specifically improve collection and accessibility of exposure data. This work should be done with a focus on cohorts where research can directly impact Veterans access to benefits and exposure-informed care.", "url": "https://pubmed.ncbi.nlm.nih.gov/41617203/" }, { "pmid": "41513981", "title": "Oleoylethanolamide supplementation improves mood and reduces fatigue in veterans with GWI in a 15-week randomized, double-blind, placebo-controlled exploratory clinical trial.", "pub_date": "2026-01-10", "journal": "Scientific reports", "authors": "Abdullah, Laila, Keegan, Andrew P, Hoffmann, Michael, Baraniuk, James et al.", "abstract": "Gulf War Illness (GWI) affects 32% of Veterans from the 1990-1991 Gulf War. It is characterized by fatigue, mood disturbances, pain and cognitive decrements, with no FDA-approved treatment. This exploratory randomized, double-blind, placebo-controlled trial evaluated the safety and efficacy of oleoylethanolamide (OEA) supplementation in 52 Veterans with GWI (mean age 59 ± 5 SD, 94% males and 79% White). Participants received 200 mg of OEA twice daily or a matching placebo for 10 weeks, followed by a 5-week open-label OEA extension. Outcomes included the Multidimensional Fatigue Inventory (MFI-20), abbreviated Profile of Mood States (POMS), Short-Form McGill Pain Questionnaire, Veterans RAND 36-Item Health Survey (SF-36 V), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and CNS Vital Signs Test, administered at baseline and 10- and 15-weeks. A main effect of OEA for reducing fatigue (MFI-20, p ≤ 0.05) and improving the total mood disturbances score (POMS, p ≤ 0.05) was observed. Participants on OEA reported increased energy, emotional well-being, and social functioning (SF-36 V, p ≤ 0.05). No changes were seen in cognitive performance or pain. Oleoylethanolamide was well-tolerated with no serious adverse events. In summary, OEA was safe and improved fatigue and mood in Veterans with GWI. Larger trials are needed to confirm these benefits.Registered under ClinicalTrials.gov Identifier no. NCT05252949 (first posted date: 23/02/2022).", "url": "https://pubmed.ncbi.nlm.nih.gov/41513981/" }, { "pmid": "41473411", "title": "Correction: Gulf war toxicant-induced effects on the hippocampal dendritic arbor are reversed by treatment with a", "pub_date": "2025-12-31", "journal": "Frontiers in neuroscience", "authors": "Shaikh, Amaan L, Murray, Kathleen E, Ravindranath, Vijayalakshmi, Citron, Bruce A", "abstract": "[This corrects the article DOI: 10.3389/fnins.2024.1368667.].", "url": "https://pubmed.ncbi.nlm.nih.gov/41473411/" }, { "pmid": "41472292", "title": "Does Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Represent a Poly-Herpesvirus Post-Virus Infectious Disease?", "pub_date": "2025-12-31", "journal": "Viruses", "authors": "Ariza, Maria Eugenia, Mena Palomo, Irene, Williams, Marshall V", "abstract": "Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem illness with unknown etiology. An estimated 17-24 million people representing approximately 1% of the population are afflicted worldwide. In over half of cases, ME/CFS onset is associated with acute \"flu-like\" symptoms, suggesting a role for viruses. However, no single virus has been identified as the only etiological agent. This may reflect the approach employed or more strongly the central dogma associated with herpesviruses replication, which states that a herpesvirus exists in two states, either lytic or latent. The purpose of this review is to address the role that abortive lytic replication may have in the pathogenesis of ME/CFS and other post-acute viral infections and also to raise awareness that these syndromes might be poly-herpesviruses mediated diseases.", "url": "https://pubmed.ncbi.nlm.nih.gov/41472292/" }, { "pmid": "41463371", "title": "Investigating the Eye as a Biomarker of Gulf War Illness: Sphingolipid and Eicosanoid Composition in Tears and Plasma.", "pub_date": "2025-12-30", "journal": "Biomolecules", "authors": "Paule Jimenez, Laura Beatriz, Prislovsky, Amanda, Parchejo, Loralei Ann, Cabrera, Kimberly et al.", "abstract": "Gulf War Illness (GWI) is a chronic multi-symptom condition affecting veterans of the 1990-1991 Gulf War, with ocular discomfort increasingly recognized among its manifestations. This pilot study evaluated whether lipid alterations in tears and plasma could serve as potential biomarkers of GWI. Participants included Gulf War-era veterans seen in the Miami Veterans Affairs Hospital eye clinic from 2018-2022. Cases met GWI criteria, while controls were non-deployed, age- and gender-matched veterans without GWI. Participants completed systemic and ocular symptom questionnaires, and lipidomic profiling of tears and plasma quantified sphingolipids and eicosanoids. Compared to controls (n = 21), GWI cases (n = 19) reported greater ocular symptom burden, while ocular signs were similar between groups. Lipidomic analyses revealed increased tear eicosanoids ((±)14(15)-EET and (±)8(9)-EET), elevated plasma sphingomyelins (SM C16:0 DH, SM C20:0, SM C22:0), and reduced plasma monohexosylceramide (MHC C16:0) and sphingomyelin (SM C14:0) in cases. Logistic regression and random forest models identified plasma SM C16:0 DH and SM C20:0 as top predictors distinguishing GWI cases from controls, with an area under the receiver operating characteristic curve (AUC) of 0.89. These findings suggest lipid dysregulation in ocular and systemic compartments and support further investigation of tears as a minimally invasive source for biomarker discovery.", "url": "https://pubmed.ncbi.nlm.nih.gov/41463371/" }, { "pmid": "41385260", "title": "The Association Between Self-Reported Types of Toxic Exposures and Symptom Severity Among Gulf War Era Veterans.", "pub_date": "2025-12-12", "journal": "Medical care", "authors": "Phan, Molly S, Winchell, Kara, Hooker, Elizabeth, Barton, Jennifer et al.", "abstract": "Gulf War illness is a chronic multisymptom illness impacting Veterans of the 1990-1991 Persian Gulf War. Toxic exposures are believed to be associated with the condition, but little is known about how multiple types of exposures can impact the disease. The aim of this study is to determine if a positive association exists between the multiplicity of exposure types and symptom severity score. A cross-sectional survey design was used in which Persian Gulf Veterans completed a questionnaire with items related to symptom severity and types of self-reported toxic exposures. Linear regression models were used to examine the association between the number of types of toxic exposures and symptom severity scores. We also examined the association between each type of reported exposure and symptom severity score. Veterans with a greater number of self-reported toxic exposures reported higher scores on symptom severity. While no individual exposure type reached a statistically significant association with symptom score, radiation and biological agent exposures showed the strongest association. We found a positive association between the number of toxic exposure types and total symptom severity. Veterans who self-reported having Gulf War Illness also reported more types of toxic exposures compared with Veterans who did not report having Gulf War Illness. Radiation and biological agent exposure showed the strongest positive association with symptom scores, yet very few Veterans reported isolated exposure of these types. Our findings suggest that cumulative exposure to multiple types of toxins could be associated with the development and severity of Gulf War Illness symptoms.", "url": "https://pubmed.ncbi.nlm.nih.gov/41385260/" }, { "pmid": "41385259", "title": "Psychiatric Conditions and Symptoms After Toxic Environmental Exposures During Military Service: An Evidence Map.", "pub_date": "2025-12-12", "journal": "Medical care", "authors": "Magnante, Anna T, Nugent, Shannon M, Bourassa, Kyle J, Leflore-Lloyd, Nina et al.", "abstract": "US service members are often exposed to a range of service-related hazards. To date, there has been limited synthesis of the existing research conducted on military environmental exposures and subsequent psychiatric conditions and symptoms. To systematically review and characterize the main features of studies examining associations between military exposures and mental health outcomes. We used evidence mapping methodology to systematically search MEDLINE, Embase, PsycINFO, and PTSDpubs for studies of toxic exposure during military service and psychiatric outcomes, which included psychiatric diagnoses, psychiatric symptoms, and neurocognitive functioning. We identified 49 studies; most were comprised of predominantly White, male veteran samples. Chemical exposures, including chemical munitions from the Gulf War era and Agent Orange from the Vietnam War era, were the most frequently examined military toxic exposures. Symptoms of depression, PTSD, and anxiety were the most commonly examined psychiatric outcomes. Only 9 studies assessed neurocognitive functioning. We found extensive variation in how exposures and outcomes were defined and measured. Most exposure and symptom data were based on self-reports. Overall, available evidence suggests that veterans reporting environmental toxic exposures may report relatively high levels of mental health needs. We found broad evidence that toxic exposure was associated with poorer mental health outcomes, though the ability to draw stronger conclusions is limited by the quality of the current literature. Future research should focus on longitudinal studies of toxic exposure and mental health that include more broadly representative military populations, including diverse samples and more recent service cohorts.", "url": "https://pubmed.ncbi.nlm.nih.gov/41385259/" }, { "pmid": "41385258", "title": "Health Care Journeys of Veterans With Gulf War Illness.", "pub_date": "2025-12-12", "journal": "Medical care", "authors": "Bloeser, Katharine, Hyde, Justeen K, Helmer, Drew A, Bolton, Rendelle E et al.", "abstract": "There is an acknowledged need to improve care for patients with persistent physical symptoms. Veterans who served in the 1990-91 Gulf War are a subpopulation of U.S. military Veterans who have been struggling with persistent physical symptoms for decades. The current study sought to characterize Veterans' historic path through the health care system and current experience of care to identify opportunities to improve care. Analysis of interviews conducted with 31 Veterans who met criteria for Gulf War Illness (GWI) was conducted to understand Veterans' health care journeys, from symptom onset to the present. Early in their journey, Veterans felt uncertain about the nature of their condition and how to explain it to clinicians. Veterans described a cycle of referrals to specialists to pursue individual symptoms and subsequent return to primary care with few actionable findings. During this cycle, Veterans often felt dismissed or invalidated by clinicians. Over time, most Veterans felt care became increasingly fragmented, with multiple clinicians caring for them without a plan to manage GWI and little acknowledgement of GWI as a discrete illness. Further in their journey, some Veterans were referred to tertiary centers where they encountered a more holistic approach. Findings point to the need to shift care for Veterans with GWI, and similar conditions, away from overly focusing on individual symptoms. Instead, primary care clinicians need training and support, potentially from tertiary care experts, to develop and implement holistic care plans that recognize GWI as a complex chronic condition.", "url": "https://pubmed.ncbi.nlm.nih.gov/41385258/" }, { "pmid": "41337155", "title": "Immune transcriptomic changes in Australian Gulf War veterans.", "pub_date": "2025-12-03", "journal": "PloS one", "authors": "Eaton-Fitch, Natalie, Sasso, Etianne Martini, Marshall-Gradisnik, Sonya", "abstract": "Gulf War Illness (GWI) is a chronic multisystemic illness found in one-third of Gulf War Veterans. The aetiology of GWI is elusive; however, is strongly associated with exposure to multiple toxic agents, environmental exposures, and prophylactic medications or vaccinations. In the literature, disruption of the immune system and the presence of inflammation have been reported in GWI. In this novel study, we report gene expression-based analysis of a panel of 785 immune function related gene markers in GWI. Ribonucleic acid (RNA) was extracted from peripheral blood mononuclear cells (PBMCs) isolated from n = 20 Australian GWI (CDC Case Definition and Kansas Criteria, 54.4 ± 0.74 years), and n = 15 healthy control (HC, 47.47 ± 2.91 years) participants. All participants were sex-matched (100% male). RNA gene expression was quantified using the NanoString® nCounter Immune Exhaustion panel and analysed using Rosalind Bio and IPA. Thirty-three differentially expressed genes were identified, of which 21 were upregulated and 12 were downregulated in the GWI cohort. Upregulated genes included SIGLEC1, BPI, MMP9, RSAD2, IFIT1/2, CEACAM1/3 and were associated with metabolic and cellular stress responses, while downregulated genes were associated with T cell receptor regions and humoral immune responses. Downregulated genes included TRDV3, IGHG1, TRGV4, TRDV1/4, and IL7. Gene set analysis revealed associations between gene expression and type I interferon signalling, natural killer receptors, T cell receptors, and tumour necrosis factor signalling. Pathway analysis revealed the role of differentially expressed genes in neutrophil signalling and degranulation, toll-like receptor cascades, and the role of lipids/lipid rafts in infection. This investigation elucidates the potential role of immune dysregulation underlying GWI, emphasising the importance of immune exhaustion pathways in disease progression. Further investigations in a larger cohort may further elucidate or confirm these identified markers for potential screening or therapeutic applications in GWI.", "url": "https://pubmed.ncbi.nlm.nih.gov/41337155/" }, { "pmid": "41266399", "title": "Decadelong low basal ganglia NAA/tCr from elevated tCr supports ATP depletion from mitochondrial dysfunction and neuroinflammation in Gulf War illness.", "pub_date": "2025-11-21", "journal": "Scientific reports", "authors": "Cheshkov, Sergey, Krishnamurthy, Lisa C, Chang, Audrey, Baek, Hyeon-Man et al.", "abstract": "Reduced N-acetylaspartate (NAA)/total creatine (tCr) ratio found with long echo-time proton magnetic resonance imaging (", "url": "https://pubmed.ncbi.nlm.nih.gov/41266399/" }, { "pmid": "41226310", "title": "Corticosteroid Usage in Modeling Gulf War Illness in Pre-Clinical Models: A Systematic Review.", "pub_date": "2025-11-13", "journal": "International journal of molecular sciences", "authors": "Tehrani, Lily, Movva, Chetana, Frank, Joshua, Nagy, Stephanie et al.", "abstract": "Gulf War Illness (GWI) is a neuroinflammation- and immune-dysfunction-related chronic disease. Corticosteroids, a class of steroid hormones with potent anti-inflammatory and immunosuppressive properties, have been studied for their role in GWI pathophysiology. Eight corticosteroid effect studies were evaluated in this systematic review. Preclinical models showed exacerbation of neuroinflammation, oxidative stress, and epigenetic changes with exposure to CORT in addition to Gulf War neurotoxicants, which induced pro-inflammatory cytokine expression (Tumor Necrosis Factor Alpha (TNF-α), Interleukin-6 (IL-6), C-C motif chemokine ligand 2 (CCL2)). Such findings suggest that corticosteroids can exacerbate symptoms of GWI and need further clinical research to clarify their role in neuroinflammatory processes.", "url": "https://pubmed.ncbi.nlm.nih.gov/41226310/" }, { "pmid": "41137912", "title": "Neurometabolite alterations in Gulf War Illness: a whole-brain magnetic resonance spectroscopy study.", "pub_date": "2025-10-25", "journal": "Experimental brain research", "authors": "Jones, Chloe, Haskin, Olivia, Younger, Jarred", "abstract": "Gulf War Illness (GWI) affects approximately 30% of veterans who served in the 1991 Persian Gulf War and is characterized by chronic pain and fatigue, as well as cognitive, mood, gastrointestinal, and respiratory symptoms. Animal research has suggested that GWI is caused by a combination of neurotoxicants such as nerve gas, anti-nerve agent pills, and pesticides, though a definitive pathophysiological model has not been established. In this human observational study, 20 veterans with GWI and 20 healthy Gulf War veterans (HV) underwent whole-brain magnetic resonance spectroscopy to non-invasively measure several metabolites associated with neuroinflammation. Veterans also completed an arterial spin labeling scan to assess cerebral perfusion. Compared to HV, veterans with GWI demonstrated widespread decreases in brain choline, N-acetylaspartate, and creatine, and regional elevations in lactate and brain temperature. No group difference was observed in cerebral perfusion. Exploratory analyses revealed brain metabolites were associated with self-reported neurotoxicant exposures in theater. These findings support a role of cholinergic alterations and neuroinflammatory processes in GWI. Trial registration: The study was registered in ClinicalTrials.gov, ID NCT04638998. Registered November 16, 2020, https://clinicaltrials.gov/study/NCT04638998 .", "url": "https://pubmed.ncbi.nlm.nih.gov/41137912/" }, { "pmid": "41102909", "title": "Assessing Veterans With Gulf War Illness for Prodromal Parkinson's Disease Risk With the REM Behavioral Sleep Disorder Questionnaire.", "pub_date": "2025-10-17", "journal": "Journal of occupational and environmental medicine", "authors": "Chao, Linda L, Stiep, Tamara, Zuzuárregui, José Rafael P", "abstract": "To assess deployed Gulf War (GW) veterans for prodromal Parkinson's Disease (PD) using the REM Sleep Behavioral Disorder (RBD) Screening Questionnaire (RBDSQ). GW veterans ( n = 165) were assessed for nonmotor PD symptoms with the RBDSQ, Non-Motor Symptoms Scale, and Scales for Outcomes in Parkinson's Disease-Autonomic. Some veterans were also assessed with the University of Pennsylvania Smell Identification Test ( n = 120), neurological examinations ( n = 41), and 3T magnetic resonance imaging ( n = 16). Eighty percent of veterans with PD and 73% of veterans without PD had probable RBD (ie, RBDSQ ≥5). Exploratory analysis conducted for hypothesis-generating purposes revealed that RBDSQ scores were positively associated with GW deployment-related exposures and inversely associated with brainstem volume. These findings suggest that veterans with GWI and high levels of deployment-related exposures are at risk for prodromal PD, possibly through RBD as a mediator.", "url": "https://pubmed.ncbi.nlm.nih.gov/41102909/" }, { "pmid": "41070007", "title": "Infectious etiologies of conjunctival tumors.", "pub_date": "2025-10-10", "journal": "Expert review of ophthalmology", "authors": "Alvarez, Osmel P, Monroy, David, Thura, Soraiya, Antonietti, Michael et al.", "abstract": "Infectious agents have been associated with a variety of conjunctival tumors, including lymphoma, ocular surface squamous neoplasia (OSSN), papilloma, and Kaposi sarcoma. We discuss the infectious etiologies of certain conjunctival tumors including conjunctival lymphoma ( It is important for the clinician to recognize when tumors of the conjunctiva may be infection-associated. A detailed history and exam are the most important first step in diagnosis; this may be supplemented by tools such as high-resolution optical coherence tomography. For some tumors, the specific causative agent may influence treatment options and outcomes. For others, data suggest the infectious agent does not influence treatment or outcomes, but it is important nonetheless to be aware as further research on these tumors continues. Additionally, there is exciting research investigating novel and minimally invasive diagnostic and treatment options for conjunctival tumors, including treatments that target the infectious agent directly.", "url": "https://pubmed.ncbi.nlm.nih.gov/41070007/" }, { "pmid": "41046639", "title": "Deployment-related toxic exposures, mental health problems, and suicide outcomes among Gulf War era U.S. veterans.", "pub_date": "2025-10-06", "journal": "Journal of psychiatric research", "authors": "Patel, Tapan A, Bourassa, Kyle J, Calhoun, Patrick S, Beckham, Jean C et al.", "abstract": "Exposure to toxins, such as pesticides, smoke from burning oil fields, and nerve gas, during military operations have been linked to poor physical health among veterans. However, less is known about how these exposures may affect mental health outcomes, especially those relevant to military populations (e.g., posttraumatic stress disorder [PTSD], depression, alcohol use disorder, suicide). The goal of the present study was to examine how any toxic exposure and total toxic exposures were associated with probable current diagnoses of PTSD, major depressive disorder, and alcohol use disorder as well as lifetime history of suicidal ideation and suicide attempts among a large national sample of Gulf War-Era veterans (N = 1153). Notably, when covarying for demographic factors, any toxic exposure was associated with increased odds of probable PTSD (AOR = 2.66), probable depression (AOR = 1.92), and suicidal ideation (AOR = 1.75), but these associations, except for suicidal ideation (AOR = 1.50), were no longer present once accounting for military covariates (i.e., combat exposure and Gulf War illness). Further, higher total number of deployment-related toxic exposures were associated with increased odds of meeting criteria for probable PTSD (AOR = 1.83), probable depression (AOR = 1.28), probable alcohol use disorder (AOR = 1.22), and of reporting suicidal ideation (AOR = 1.22), even after accounting for both demographic and military covariates. Our findings suggest that self-reported toxic exposures are uniquely related to worse mental health problems after military service.", "url": "https://pubmed.ncbi.nlm.nih.gov/41046639/" }, { "pmid": "41009608", "title": "Gulf War Illness, Fibromyalgia, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID Overlap in Common Symptoms and Underlying Biological Mechanisms: Implications for Future Therapeutic Strategies.", "pub_date": "2025-09-27", "journal": "International journal of molecular sciences", "authors": "Mantle, David, Domingo, Joan Carles, Golomb, Beatrice Alexandra, Castro-Marrero, Jesús", "abstract": "Although Gulf War Illness (GWI), fibromyalgia (FM), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID have distinct origins, in this article we have reviewed evidence that these disorders comprise a group of so-called low-energy associated disorders with overlapping common symptoms underlying pathology. In particular, evidence for mitochondrial dysfunction, oxidative stress, inflammation, immune dysregulation, neuroendocrine dysfunction, disrupted brain-gut-microbiome axis, apoptosis/ferroptosis and telomere shortening as common features in the pathogenesis of these disorders has been identified. Given the role of coenzyme Q10 (CoQ10) in promoting normal mitochondrial function, as an antioxidant, antiinflammatory and antiapoptotic and antiferroptotic agent, there is a rationale for supplementary CoQ10 in the management of these disorders. The reported benefits of supplementary CoQ10 administration in GWI, FM, ME/CFS and long COVID have been reviewed; the potential benefit of supplementary CoQ10 in reducing telomere shortening and improving the efficiency of stem cell transfer relevant has also been identified as promising therapeutic strategies in these disorders. This review advances beyond previous systematic reviews and consensus statements on overlapping similar symptoms and underlying biological pathomechanisms in these complex disorders.", "url": "https://pubmed.ncbi.nlm.nih.gov/41009608/" }, { "pmid": "40990886", "title": "Global, Regional, and National Burden of Cardiovascular Diseases and Risk Factors in 204 Countries and Territories, 1990-2023.", "pub_date": "2025-09-24", "journal": "Journal of the American College of Cardiology", "authors": "Authors not listed", "abstract": "Cardiovascular diseases (CVDs) are the leading cause of mortality and are among the foremost causes of disability globally. CVD burden has continued to increase in most countries since 1990, with trends driven by changing exposures to harmful risk factors, population growth, and population aging. We report estimates of global, national, and subnational CVD burden, including 18 subdiseases and 12 associated modifiable risk factors. We analyzed change in CVD burden from 1990 to 2023 and identified drivers of change including population growth, population aging, and risk factor exposure. The Global Burden of Disease (GBD) 2023 study, a multinational collaborative research study, quantified burden due to 375 diseases including CVD burden and identified drivers of change from 1990 to 2023 using all available data and statistical models. GBD 2023 estimated the population-level burden of diseases in 204 countries and territories from 1990 to 2023. CVDs were the leading cause of disability-adjusted life years (DALYs) and deaths estimated in the GBD. As of 2023, there were 437 million (95% UI: 401 to 465 million) CVD DALYs globally, a 1.4-fold increase from the number in 1990 of 320 million (292 to 344 million). Ischemic heart disease, intracerebral hemorrhage, ischemic stroke, and hypertensive heart disease were the leading cardiovascular causes of DALYs in 2023 globally. As of 2023, age-standardized CVD DALY rates were highest in low and low-middle Socio-demographic Index (SDI) settings and lowest in high SDI settings. The number of CVD deaths increased globally from 13.1 million (95% UI: 12.2 to 14.0 million) in 1990 to 19.2 million (95% UI: 17.4 to 20.4 million) in 2023. The number of prevalent cases of CVD more than doubled since 1990, with 311 million (95% UI: 294 to 333 million) prevalent cases of CVD in 1990 and 626 million (95% UI: 591 to 672 million) prevalent cases in 2023 globally. A total of 79.6% (95% UI: 75.7% to 82.5%) of CVD burden is attributable to modifiable risk factors 347 million [95% UI: 318 to 373 million] DALYs in 2023). Globally, high systolic blood pressure, dietary risks, high low-density lipoprotein cholesterol, and air pollution were the modifiable risks responsible for most attributable CVD burden in 2023. Since 1990, changes in exposure to modifiable risk factors have had mixed effects on CVD burden, with increases in high body mass index, high fasting plasma glucose, and low physical activity leading to higher burden, while reductions in tobacco usage have mitigated some of these increases. Population growth and population aging were the main drivers of the increasing burden since 1990, adding 128 million (95% UI: 115 to 139 million) and 139 million (95% UI: 126 to 151 million) CVD DALYs to the increase in CVD burden since 1990. CVD remains the leading cause of disease burden and death worldwide with the greatest burden in low, low-middle, and middle SDI regions. Large variation exists in CVD burden even for countries at similar levels of development, a gap explained substantially by known, modifiable risk factors that are inadequately controlled. The decades-long increase in CVD burden was the result of population growth, population aging, and increased exposure to a subset of risk factors led by metabolic risks. Countries will need to adopt effective health system and public health strategies if they are to progress in achieving global goals to reduce the burden of CVD.", "url": "https://pubmed.ncbi.nlm.nih.gov/40990886/" }, { "pmid": "40972072", "title": "Actual concordance between veterans' with Gulf War Illness and their providers' illness perceptions is not related to patient satisfaction nor treatment adherence.", "pub_date": "2025-09-19", "journal": "Patient education and counseling", "authors": "Boska, Rachel L, Phillips, L Alison, Lesnewich, Laura M, Bloeser, Katharine J et al.", "abstract": "Patients with persistent physical symptom (PPS) conditions, such as Gulf War Illness (GWI), report disagreement or \"non-concordance\" with their providers about PPS conditions and dissatisfaction with healthcare. When patients perceive concordance with their providers about their PPS condition, they have increased satisfaction and adherence. While literature supports perceived concordance, there is a lack of research on actual concordance (i.e., the congruence of patients' and providers' perceptions of the patients' illness). Among dyads of Veterans with GWI and their provider, we tested the hypotheses that greater actual concordance would be associated with greater Veterans' satisfaction and adherence. We also explored the relationship of actual concordance with Veterans' and providers' perceived concordance. Correlations suggest there is little agreement between Veterans and providers regarding GWI illness perceptions or perceptions of concordance. Polynomial regression analyses showed that actual concordance was not significantly related to Veterans' satisfaction, adherence, or perceptions of concordance, nor to providers' perceptions of concordance. Although literature finds Veterans' perceived concordance with their provider about PPS influences patients' experiences of care, our results suggest that actual concordance may have limited influence on experiences of care and either Veterans' or providers' perceived concordance. That is, the results suggest there does not need to be objective agreement between patients and providers about PPS, rather patients' perception of agreement influences their satisfaction and adherence. Our results suggest that patients with PPS and their providers may have difficulties in estimating if there is shared agreement in the relationship and demonstrate the importance of explicitly assessing patients' perceptions of concordance.", "url": "https://pubmed.ncbi.nlm.nih.gov/40972072/" }, { "pmid": "40943436", "title": "Evaluation of the Therapeutic Potential of Synthetic Growth Hormone-Releasing Hormone Antagonist MIA-690 as a Cognitive Modulator in a Mouse Model of Gulf War Illness.", "pub_date": "2025-09-13", "journal": "International journal of molecular sciences", "authors": "Salgueiro-Tosta, Luis Manuel, Jayakumar, Arumugam Radhakrishnan, Kochen, William, Cai, Renzhi et al.", "abstract": "Gulf War illness (GWI) is a multi-symptom disorder affecting veterans of the Persian Gulf operations. Persistent neuroendocrine dysregulation contributes to impairing cognitive capacity and generates anxiety-like behavior. Effective treatments for this illness are challenging due to compromised metabolism, increased oxidative stress and neuroinflammation, perpetuated by chronic stress and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. This neuroinflammation can be alleviated with synthetic antagonistic analogs of the growth hormone-releasing hormone (GHRH) through modulation of the HPA axis. We evaluated the efficacy of the GHRH antagonist analog, MIA-690, against cognitive impairment and anxiety-like behavior in GWI. Mice exposed to an experimental GWI model involving corticosterone (CORT) and diisopropylfluorophosphate (DFP), followed by CORT and lipopolysaccharide (LPS), received a daily subcutaneous dose of 10 μg of MIA-690 for 10 days. Assessments of spatial memory, recognition capacity, somatic health, anxiety and innate survival were carried out, combining the Morris water maze (MWM), novel object recognition (NORT), grip strength (GST), and open field (OFT) tests. Learning efficiency was selectively enhanced in females using the MWM. There were no significant differences in the recall capacity and performance on the OFT, NOR, and GST tasks. Our findings suggest that the MIA-690 dosage is sufficient to improve learning deficits in experimental GWI exposures.", "url": "https://pubmed.ncbi.nlm.nih.gov/40943436/" }, { "pmid": "40927423", "title": "Fatigue, interoplastic and nociplastic distress in myalgic encephalomyelitis/chronic fatigue syndrome, Gulf War Illness, and chronic idiopathic fatigue.", "pub_date": "2025-09-10", "journal": "Frontiers in neuroscience", "authors": "Chen, Emily, Rudder, Tamera, Nwankwere, Charles, Baraniuk, James N", "abstract": "Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Gulf War Illness (GWI) have similar profiles of pain (nociception), visceral interoception, and tenderness (central sensitization) that may be due to dysfunction of midbrain and medulla descending antinociceptive and antiinteroceptive mechanisms. If so, then dolorimetry, a proxy for tenderness, may be correlated with subjective symptoms. The relationship with fatigue was assessed in Chronic Idiopathic Fatigue (CIF). Cohorts of ME/CFS, GWI, and sedentary control subjects completed questionnaires and had dolorimetry. Spearman correlations were calculated between central sensitization (dolorimetry), fatigue (Chalder Fatigue), pain (McGill Pain), interoception (Chronic Multisymptom Inventory), disability (SF36), psychological constructs, and other symptoms. Females were more tender than males and were thus analyzed separately. GWI and ME/CFS groups were more tender than controls for females ( The outcomes generate several hypotheses about ME/CFS and GWI pathophysiology. Disease pathologies may involve injury to midbrain and medulla regulatory pathways causing central sensitization with the loss of descending antiinteroceptive and antinociceptive inhibitory mechanisms and increased perceptions of widespread visceral complaints and pain. The diseases can be re-conceptualized as chronic disabling fatigue with heightened interoceptive and nociceptive symptoms. Variations in antiinteroceptive control may provoke unpredictable shifts in symptom spectrum and severity that contribute to exertional exhaustion and symptom exacerbation. Subjective criteria were found to define CIF prospectively.", "url": "https://pubmed.ncbi.nlm.nih.gov/40927423/" }, { "pmid": "40912694", "title": "Upper gastrointestinal symptoms and Gulf War Illness in a clinical cohort of US veterans: a retrospective, cross-sectional study.", "pub_date": "2025-09-06", "journal": "BMJ open gastroenterology", "authors": "Yousef, Abdelrahman, Ahmed, Sarah T, H Nguyen Wenker, Theresa, Nono-Djotsa, Alice B S et al.", "abstract": "Approximately 30% of the 700 000 US Gulf War Veterans (GWVs) report symptoms collectively termed Gulf War Illness (GWI), a multisymptom illness of uncertain pathophysiology. Prior studies in GWI focus on overlap with irritable bowel syndrome. This study examines the associations between upper gastrointestinal (UGI) symptoms, GWI and specialty GI care. This cross-sectional study analysed GWVs referred to a Veterans Health Administration clinical War-Related Illness and Injury Study Center (2008-2020). Symptoms, demographics, military service and clinical history were obtained from self-reported intake packets. GWI was defined by the Centers for Disease Control and Prevention criteria requiring moderate-to-severe symptoms in at least two of three domains: fatigue, musculoskeletal and mood cognition. UGI symptoms were analysed individually as a composite variable and additively (0-5). Logistic regression models estimated ORs for associations between UGI symptoms, GWI and GI specialty care. The cohort included 596 GWVs (mean age 49.3 years, 88% men). Most (93.5%) reported at least one UGI symptom, with a mean of 2.8 symptoms. GWI was identified in 413 (69%). Veterans with GWI were more likely to report UGI symptoms (98.3% vs 82.5%) and had a higher mean symptom count (3.1 vs 2.1). Adjusted ORs for UGI symptoms in GWI ranged from 1.79 (dysphagia) to 3.57 (nausea/vomiting). UGI symptoms are common among GWVs and strongly associated with GWI. Clinicians should screen for UGI symptoms and follow standard protocols for treatment and referral.", "url": "https://pubmed.ncbi.nlm.nih.gov/40912694/" }, { "pmid": "40911267", "title": "Chronic Ocular Surface Pain: An Optometrist and Ophthalmologist Survey.", "pub_date": "2025-09-05", "journal": "Ophthalmology and therapy", "authors": "Galor, Anat, Abbott, Kaleb, Henderson, Bonnie, Pflugfelder, Steve et al.", "abstract": "Chronic ocular surface pain (COSP) is defined as ocular pain that is perceived to originate from the ocular surface and persists for more than 3 months. Clear epidemiological data on COSP prevalence are lacking. In 2025, a total of 100 eye care providers were surveyed, including 50 optometrists and 50 ophthalmologists. The survey aimed to assess the percentage of their weekly patient volume diagnosed with COSP, the diagnostic methods used, contributing etiologies, and current management strategies. Additionally, practitioners identified key indicators of successful treatment and attributes they believed would have the greatest impact on patient outcomes. Lastly, they rated their satisfaction with current therapeutic options. An estimated 33% of optometrists' patients and 29% of ophthalmologists' patients had COSP. Of those diagnosed with dry eye disease (DED), 63% also had COSP. Providers managed COSP with over-the-counter (OTC) artificial tears (97% of respondents), OTC gels and ointments (90%), hot compresses (86%), and prescription therapies indicated for DED (30-88%), while a minority routinely used amniotic membranes (37%), serum tears (26%), intense pulsed light (18%), and LipiFlow (16%). The proportions of providers who were satisfied or very satisfied with these therapies were as follows: 64% for amniotic membranes and serum tears, 63% for device-based therapies, 40% for prescription medications, and 21% for OTC drops, ointments, and hot compresses. This survey provides initial insight into the prevalence of COSP among patients in US eye care clinics, along with perspectives on managing this condition from both optometrists and ophthalmologists. The most common therapeutic strategies for COSP (OTC artificial tears, gels, and ointments) were associated with the lowest levels of provider satisfaction. COSP and dry eye disease are distinct but closely linked conditions. These results demonstrate an unmet need for new treatment options to address COSP. Chronic ocular surface pain (COSP) refers to eye pain that starts at the surface of the eye and lasts for more than 3 months. Currently, there is a lack of clear data on how common this condition is. To better understand COSP, we surveyed 50 optometrists and 50 ophthalmologists in the United States in 2025. The responders estimated that about one-third of their patients had COSP. Among patients with dry eye disease, nearly two-thirds also experienced COSP. The survey explored how providers diagnose and treat COSP, and what factors they believe lead to better outcomes. Most commonly, COSP was managed using over-the-counter (OTC) artificial tears, gels and ointments, and hot compresses along with prescription treatments for dry eye. More advanced therapies like amniotic membranes, serum tears, and devices such as intense pulsed light and LipiFlow were also listed as options. Despite the widespread use of OTC treatments and prescription dry eye treatments for COSP, providers reported the lowest satisfaction with these options. Overall, this survey sheds light on how common COSP is, the need for it to be a disease distinguished from DED despite having similar symptoms, and the importance of properly diagnosing COSP. The findings reveal a gap between frequently used options for managing COSP and provider satisfaction, pointing to a strong need for better therapies to manage chronic ocular surface pain.", "url": "https://pubmed.ncbi.nlm.nih.gov/40911267/" }, { "pmid": "40829313", "title": "Age- and sex-associated effects of C18 ceramide sphingolipids on osteoclastogenesis in experimental models of Gulf War Illness.", "pub_date": "2025-08-20", "journal": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie", "authors": "Yamada, Chiaki, Nusbaum, Amilia, Sanz, Natasha, AlQallaf, Hawra et al.", "abstract": "Approximately 60 % of Gulf War Illness (GWI) cases are correlated with toxic exposure to permethrin (PER) and pyridostigmine bromide (PB) in Veterans. Among the known hallmarks of GWI, pathological changes in bone of Veterans with GWI are poorly understood due to the lack of relevant experimental models of osteoclastogenesis. Emerging metabolomic studies have reported that GWI symptoms are positively correlated with the accelerated prevalence of ceramide sphingolipids in the serum. According to a secondary analysis of publicly available targeted metabolomic datasets, the area under the curve (AUC) value of C18:0 ceramide was significantly elevated by more than 56 % in the serum of male GWI Veterans compared to non-veteran healthy controls. Using mouse bone marrow-derived osteoclast precursors from young (2-month-old) and aged (22-month-old) mice, our observational studies confirmed that C18:0 and C18:1 significantly accelerated RANKL-primed osteoclastogenesis in vitro. Furthermore, C18:0 ceramide increased RANKL-primed osteoclast formation in aged, but not young male osteoclast precursors exposed to PB or PER in vitro. In contrast, a mixture of C18:0 and C18:1 with PB reduced the number of osteoclasts from young female mice in vitro. In addition, C18:1 diminished RANKL-primed osteoclastogenesis in young male as well as young and aged female mouse osteoclast precursors in the presence of PER in vitro. As Veterans with GWI rapidly approach the senior 65+ age range, further studies are warranted to evaluate the potential link between Gulf War toxic exposure and ceramide sphingolipids in age- and sex-associated osteoclastogenesis.", "url": "https://pubmed.ncbi.nlm.nih.gov/40829313/" }, { "pmid": "40818662", "title": "Modeling Gulf War Illness: anxiety, memory deficits, cholinergic and potassium channel imbalance in male and female mice.", "pub_date": "2025-08-17", "journal": "Life sciences", "authors": "Marrero Valentín, José L, Tosado-Rodríguez, Eduardo L, Carrasquillo Carrión, Kelvin, Pérez, Dinely et al.", "abstract": "Gulf War Illness (GWI) is a complex, multisystem condition that remains difficult to diagnose, with an etiology thought to involve interactions between stress and exposure to acetylcholinesterase (AChE) inhibitors of varying potency. Although rodent models using GWI-related neurotoxicants have been developed, many do not fully replicate war-theater conditions, particularly the inclusion of sarin exposure. We modeled a GW-like exposure in male and female C57BL/6J mice using pyridostigmine bromide (PB), permethrin (PER), N,N-diethyl-meta-toluamide (DEET), moderate stress, and Diisopropylfluorophosphate (DFP), a sarin analog. GW-like exposure initiated early symptoms of anxiety-like behavior and disrupted hippocampal-dependent spatial learning and memory retrieval across the studied cohorts. Short-term recognition memory deficits were observed in both sexes, while long-term memory impairment was limited to females. To investigate the biological basis of the observed behavioral deficits, we performed complementary analyses. In males, western blot analysis revealed a > 50% reduction in nicotinic receptor (α4β2 AChR) and potassium ion channels (Kv2.2 and Kir7.1) expression, suggesting compromised cholinergic modulation of neuronal excitability. In females, muscarinic receptor (M", "url": "https://pubmed.ncbi.nlm.nih.gov/40818662/" }, { "pmid": "40786363", "title": "Mitochondrial Impairment in Healthy Controls With Recent Headache and Multiple Symptoms.", "pub_date": "2025-08-11", "journal": "Cureus", "authors": "Golomb, Beatrice A, Situ, Jessica Y, Hamilton, Gavin", "abstract": "Persistent headache and multiple symptoms have each been tied to mitochondrial dysfunction. We assess whether reported recent headache and multiple symptoms (last two weeks) relate to bioenergetics in individuals who do not meet criteria for chronic multisymptom illness (CMI). Twenty participants screening negative for CMI rated the presence/absence and severity (0-10) of recent (last two weeks) headache and multiple symptoms and underwent Eighteen of 20 participants successfully depressed PCr (on Recent headache and multiple symptoms were related to prolonged post-exercise PCr-recovery in persons screening negative for CMI. Future studies should distinguish among potential foundations for these associations.", "url": "https://pubmed.ncbi.nlm.nih.gov/40786363/" }, { "pmid": "40732283", "title": "Navigating the Dry Eye Therapeutic Puzzle: A Mechanism-Based Overview of Current Treatments.", "pub_date": "2025-07-30", "journal": "Pharmaceuticals (Basel, Switzerland)", "authors": "Betz, Jason, Galor, Anat", "abstract": "No abstract available.", "url": "https://pubmed.ncbi.nlm.nih.gov/40732283/" }, { "pmid": "40620354", "title": "Editorial: Brain dysfunction in Gulf War illness: pathophysiology and treatment.", "pub_date": "2025-07-07", "journal": "Frontiers in neuroscience", "authors": "Shetty, Ashok K, Sullivan, Kimberly, Qiang, Liang", "abstract": "No abstract available.", "url": "https://pubmed.ncbi.nlm.nih.gov/40620354/" }, { "pmid": "40606660", "title": "Epigenetic study of the long-term effects of gulf War illness.", "pub_date": "2025-07-03", "journal": "Frontiers in genetics", "authors": "Jones, B C, O'Callaghan, J P, Ashbrook, D G, Lu, L et al.", "abstract": "Gulf War Illness is a chronic multisymptomatic disorder that affects as many as 25-35% of the military personnel who were sent to the Persian Gulf war in 1991. The illness has many debilitating symptoms, including cognitive problems, gastrointestinal symptoms, and musculoskeletal pain. Those so afflicted have been sick for more than 30 years and, therefore, it has become imperative to understand the etiology of Gulf War Illness and then produce treatments to ease the symptoms. We hypothesized that the length of the disease was reflected in epigenetic modification of possibly several genes related to the symptoms. We subjected male and female mice from 11 BXD strains to combined corticosterone and the sarin surrogate, diisopropylfluorophosphate, to emulate the physiological stress of war and the potential exposures to organophosphate pesticides and nerve agent in theater. Three hundred days after treatment, we used Methyl-CpG-binding domain sequencing (MBD-seq) to assay genome-wide methylation. The analysis revealed 20 methylated genes, notably Eif2b5, that regulates myelin production. Loss of myelin with accompanying musculoskeletal pain is a major symptom of Gulf War Illness. Our work demonstrates multiple genes were methylated by exposure to organophosphates and glucocorticoids. These genes point to biochemical mechanisms that may be targets for therapeutic intervention.", "url": "https://pubmed.ncbi.nlm.nih.gov/40606660/" }, { "pmid": "40579044", "title": "DTI-Derived Evaluation of Glymphatic System Function in Veterans with Chronic Multisymptom Illness.", "pub_date": "2025-06-28", "journal": "AJNR. American journal of neuroradiology", "authors": "Zhang, Yu, Moore, Matthew, Rahimpour, Yashar, Clark, J David et al.", "abstract": "Chronic multisymptom illness (CMI) includes symptoms of fatigue, pain, and sleep difficulties, as well as neurologic, respiratory, and gastrointestinal problems and is particularly common in veterans from the 1990-1991 Gulf War and the Afghanistan and Iraq Wars. Glymphatic system function may play an important role in the etiopathology of CMI but has not been addressed. DTI-derived analysis along the perivascular space provides a promising proxy for glymphatic system function by evaluating the status of perivascular space fluid flow. The objective of this study was to compare this DTI-derived glymphatic index in veterans with CMI and healthy controls, and to reveal possible correlations between this index and the severity of CMI symptoms. DTI-derived indices were extracted from imaging data of 203 veterans who met clinical diagnostic criteria for CMI, and 224 age-matched healthy control subjects from multiple public research databases. Severity of CMI, sleep difficulty, pain intensity, and the degree of chronic fatigue were based on self-report measures. MRI scanner and site variations were harmonized. Statistical analyses were performed adjusting for demographic confounding factors. Both healthy controls and veterans showed significantly reduced glymphatic indices associated with increased age. Compared with controls, veterans showed bilaterally lower indices (Cohen This study suggests that impaired glymphatic functions are strongly associated with CMI. These findings improve our understanding of the pathologic mechanism underlying CMI and point to DTI-based metrics as a potential biomarker for disease severity in this condition.", "url": "https://pubmed.ncbi.nlm.nih.gov/40579044/" }, { "pmid": "40568571", "title": "Comprehensive examination of resting state fMRI connectomics yields new insights into brain function deficits in Gulf War illness after accounting for heterogeneity in brain impairment across the ill veteran population.", "pub_date": "2025-06-26", "journal": "Neuroimage. Reports", "authors": "Yang, Guangming, Haley, Robert W, Guo, Ying, Gopinath, Kaundinya S", "abstract": "An estimated 200,000 veterans (up to 32% of those deployed) of the 1991 Gulf War (GW) suffer from GW illness (GWI), an incompletely understood chronic medical condition, characterized by multiple symptoms indicative of brain function deficits in various domains. Epidemiologic and animal studies have associated GWI with exposure to neurotoxic chemicals such as nerve agents, organophosphate pesticides and pyridostigmine bromide. One factor that hampers mechanistic investigations into GWI is that there is considerable heterogeneity in brain impairments across the ill GW veteran population. This could reflect the underlying heterogeneity in both exposure to neurotoxic substances, as well as genetic predisposition or resistance to neurotoxicity. Only one of the validated case definitions, the Haley GWI criteria addresses this heterogeneity. It does so by breaking down GWI into three main syndrome variants (GWS1, GWS2, and GWS3) based on factor analysis of symptoms presented by GWI veterans. Resting state fMRI (rsfMRI) is a uniquely useful brain imaging technique in that in a 10-min fMRI scan it can probe numerous brain function domains simultaneously. In this study, we employed a connectomics approach and machine learning on rsfMRI data from a cohort of GW veterans to extract neuroimaging biomarkers specific to each of the three Haley GWI syndromes. Our results revealed a number of new insights into brain function impairment specific to each syndrome group. The findings indicate that these deficits may by and large be driven by brain mechanisms. We also found that pooling the data of all three syndromes in GWI group, as is done by commonly employed case definitions of GWI resulted in failure to detect the fMRI signatures of a lot of these brain impairments.", "url": "https://pubmed.ncbi.nlm.nih.gov/40568571/" }, { "pmid": "40552248", "title": "Subepithelial Lesions of the Ocular Surface: A Review.", "pub_date": "2025-06-24", "journal": "Current ophthalmology reports", "authors": "Najdawi, Wisam, Li, Wendy J, De Arrigunaga, Sofia, Amer, Mona M et al.", "abstract": "Subepithelial lesions of the ocular surface represent a diverse group of pathologies which may be difficult to diagnose clinically. Some of these lesions are relatively uncommon, may result in systemic manifestations, or occur secondary to systemic disease. The purpose of this review is to summarize current approaches to the diagnosis and management of six subepithelial conjunctival lesions. The standard for the diagnosis of subconjunctival lesions remains histopathologic evaluation; however, high-resolution anterior segment optical coherence tomography (HR-OCT) is a useful supplemental diagnostic tool that may facilitate diagnosis. Recent advancements in the management of subconjunctival lesions include targeted systemic therapies in conjunctival melanoma and ultra-low dose radiation radiotherapy in conjunctival lymphoma. The development of HR-OCT has provided clinicians with valuable supplemental diagnostic information to guide the diagnosis of subepithelial lesions. Additionally, novel treatment modalities may provide an alternative to traditional surgical interventions in some pathologies.", "url": "https://pubmed.ncbi.nlm.nih.gov/40552248/" }, { "pmid": "40544605", "title": "Mitochondria-targeted therapy with metformin and MitoQ reduces oxidative stress, improves mitochondrial function, and restores metabolic homeostasis in a murine model of Gulf War Illness.", "pub_date": "2025-06-23", "journal": "Redox biology", "authors": "Cai, Lun, Swetha, Mundanattu, Raji, Abraham, Terry, Alvin V et al.", "abstract": "Gulf War Illness (GWI) is a cluster of medically unexplained chronic symptoms, including neurological and gastrointestinal impairments, and muscle fatigue, suffered by veterans of the Persian Gulf War. A GWI model in C57BL/6 mice exposed to the nerve gas prophylactic pyridostigmine-bromide (PB) and the insecticide permethrin (PER) was used to test the effect of mitochondria-potentiating agents, metformin and MitoQ on chronic fatigue, observed in GWI. The exposure of mice to PB/PER resulted in enhanced oxidative stress, impaired mitochondrial function, and reduced autophagy. Treatment with the anti-diabetic drug metformin and the mitochondria-targeted antioxidant available as a dietary supplement, MitoQ, activated the AMPK signaling, reduced oxidative stress, and attenuated inflammation in gastrocnemius muscle tissue compared to untreated mice. The combination of metformin and MitoQ was found to be more effective than the individual treatments in activating AMPK. The combination treatment rescued autophagy and improved mitochondrial respiration. Chronic fatigue assessments by the hanging wire and rotarod tests, and voluntary wheel running activities showed improved physical activity/strength in mice treated with metformin and MitoQ. The results suggest the potential therapeutic benefit of a combination formulation of metformin and MitoQ in addressing the molecular and energetic impairments of skeletal muscle in GWI.", "url": "https://pubmed.ncbi.nlm.nih.gov/40544605/" }, { "pmid": "40541470", "title": "Military Exposures and Early Menopause: Findings From the Gulf War Era Cohort Study (GWECS).", "pub_date": "2025-06-21", "journal": "Women's health issues : official publication of the Jacobs Institute of Women's Health", "authors": "Gibson, Carolyn J, Cao, Guichan, Inslicht, Sabra, Altman, Allison D et al.", "abstract": "Traumatic and environmental exposures during military service may affect reproductive health and ovarian aging, putting women veterans at risk for early menopause. We examined relationships between military exposures and possible early menopause among women 1990-1991 Gulf War veterans. This is a longitudinal analysis of data from the Gulf War Era Cohort Study. Women Gulf War veterans who completed baseline (1995) and follow-up assessments (2012) and were aged ≤45 at follow-up were included. Military exposures (Gulf War deployment, military environmental exposures [MEEs], Gulf War Illness, military sexual trauma [MST]) and posttraumatic stress disorder (PTSD) were assessed at baseline. Participants were categorized as having possible early menopause if in response to follow-up survey questions about menstruation they indicated menopause or having no periods for 1 year. Associations among military exposures, PTSD, and possible early menopause were examined with logistic regression models. The analytic sample included 668 women veterans. Among Gulf War-deployed veterans (n = 384), 63% reported MEEs and 26% reported MST during deployment. Within the total sample, 57% met criteria for Gulf War Illness, and 23% met criteria for probable PTSD. At follow-up, 15% had possible early menopause. In adjusted analyses, Gulf War Illness (odds ratio [OR] 1.83; 95% confidence interval [CI] [1.14, 2.95]) and probable PTSD (OR 2.45; 95% CI [1.54, 3.90]) were significantly associated with possible early menopause. Women veterans may be vulnerable to early menopause (under age 45), which brings additional care considerations for health promotion and symptom management. Menopause care in the Department of Veterans Affairs should include consideration of PTSD and comorbid chronic conditions such as Gulf War Illness, key veteran-centric clinical correlates that may influence the onset and experience of menopause.", "url": "https://pubmed.ncbi.nlm.nih.gov/40541470/" }, { "pmid": "40470637", "title": "Physical Activity and Functioning Following Tai Chi and a Wellness Comparison Intervention in Veterans with Gulf War Illness.", "pub_date": "2025-06-05", "journal": "Behavioral medicine (Washington, D.C.)", "authors": "Polizzi, Craig P, Katz, Emma, Ting, Maria, Busser, Cameron et al.", "abstract": "Gulf War Illness (GWI) is a highly prevalent chronic, multisymptomatic condition associated with worsening physical health and quality of life among veterans. Specifically, GWI symptoms may disrupt physical functioning that negatively impacts overall health. Complementary and integrative health interventions that promote physical activity, such as Tai Chi, may be critical to addressing physical functioning in veterans with GWI. The present study is a secondary analysis of data from a randomized controlled trial comparing Tai Chi to a Wellness intervention on physical functioning outcomes in a sample of 53 veterans with GWI and pain. Gait speed, fast walking speed, lower body strength, and self-reported physical activity were assessed across four timepoints: baseline, posttreatment, 3-month follow-up, and 9-month follow-up. Treatments were delivered in a 60-minute group format twice a week for 12 weeks (24 sessions total). Results from multilevel regression models revealed that Tai Chi was related to greater increases in time spent on flexibility exercise whereas improvements in gait speed were associated with Wellness, though between-treatment differences were small. These findings are promising because they provide preliminary evidence for the utility of", "url": "https://pubmed.ncbi.nlm.nih.gov/40470637/" }, { "pmid": "40466902", "title": "Resveratrol ameliorates cognitive impairment with improvement of gut microbiota, inflammation, neurogenesis, and synaptic proteins in a mouse model of Gulf War Illness.", "pub_date": "2025-06-05", "journal": "European journal of pharmacology", "authors": "Li, Yanna, Wang, Xinyi, Yuan, Linying, Liu, Zhihui et al.", "abstract": "The main symptoms of chronic Gulf War illness (GWI) include persistent cognitive and mood impairments. Research on animals has corroborated that these cognitive and mood dysfunctions coincide with chronic neuroinflammation, declined neurogenesis, and synaptic integrity in the hippocampus. Furthermore, these neurological changes are linked with systemic inflammation and gut dysbiosis, defined by shifts in gut microbiota composition and increased intestinal permeability. Resveratrol (RSV), known for its neuroprotective properties, is currently being studied in a clinical trial for its potential to ease the symptoms in GWI veterans. Herein, we investigated whether RSV would improve cognitive and mood function in a mouse model of GWI and delved into the underlying mechanisms at play. Five months after exposure to 0.7 mg/kg pyridostigmine bromide (PB) and 200 mg/kg permethrin (PER), a two-week regimen of RSV at doses of 20 or 40 mg/kg alleviated the cognitive deficits observed in the object location and novel object recognition tests. RSV treatment effectively mitigates cognitive disorders through multiple mechanisms: (1) amelioration of gut microbiota dysbiosis and intestinal permeability; (2) downregulation of serum proinflammatory cytokine levels; (3) suppression of chronic neuroinflammation in the hippocampus, evidenced by reduced astrocyte hypertrophy, microglial activation, and neuroinflammatory markers; (4) promotion of hippocampal neurogenesis; and (5) normalization of synaptic protein levels, including PSD95, CaMKIIα. This study provides novel insights into the potential of RSV to alleviate cognitive impairment, alongside the restoration of gut dysbiosis, in veterans suffering from GWI.", "url": "https://pubmed.ncbi.nlm.nih.gov/40466902/" }, { "pmid": "40392130", "title": "Reactivation of Latent Herpesviruses and a Faulty Antiviral Response may Contribute to Chronic Multi-Symptom and Multi-System Illnesses in U.S. Military Veterans.", "pub_date": "2025-05-20", "journal": "Journal of medical virology", "authors": "Cox, Brandon, Goolkasian, Paula, Palomo, Irene Mena, Williams, Marshall V et al.", "abstract": "Chronic multi-symptom illness (CMI) is a broad term utilized by the Department of Veterans Affairs to refer to complex conditions of unknown etiology where individuals experience symptoms that lack a clear medical diagnosis. In this study, we sought to determine if herpesvirus reactivation and the antiviral response could be involved in CMI. Longitudinal serology studies conducted in two military veteran cohorts diagnosed with CMI or Gulf War Illness (GWI) revealed an increased prevalence of IgG (55% and 83%, respectively) and IgM antibodies (80%-90% and 100%, respectively) to the deoxyuridine triphosphate nucleotidohydrolase (dUTPase) protein of multiple herpesviruses compared to age/gender-matched healthy controls (5% and 7% for IgG and IgM respectively, p < 0.001) by ELISA. Despite the ongoing viral reactivation in CMI veterans, IFN-γ levels surprisingly stayed mostly unchanged from healthy control levels, while in GWI were significantly upregulated. Interestingly, MCP-1/CCL-2 levels were significantly increased in some CMI veterans compared to GWI and healthy controls (p = 0.0009). Our data provide evidence suggesting aberrant antiviral response and immune dysfunction in CMI veterans and supports the premise that decreased serum levels of IFN-γ together with heightened MCP-1 and dUTPase antibodies to multiple herpesviruses may be useful to identify CMI veterans with deficient antiviral response.", "url": "https://pubmed.ncbi.nlm.nih.gov/40392130/" }, { "pmid": "40385525", "title": "Physical Activity and Suicidal Ideation Among Gulf War Era Veterans.", "pub_date": "2025-05-19", "journal": "American journal of lifestyle medicine", "authors": "McRae Calhoun, E, Wiese, Jack D, Meckes, Samantha J, Grove, Jeremy L et al.", "abstract": "This study from a national sample of Gulf War Veterans (", "url": "https://pubmed.ncbi.nlm.nih.gov/40385525/" }, { "pmid": "40366759", "title": "Unraveling the genetics of gulf war illness in diverse participants enrolled in the million veteran program.", "pub_date": "2025-05-14", "journal": "Human molecular genetics", "authors": "Pathak, Gita A, Koller, Dora, Cabrera-Mendoza, Brenda, Nono Djotsa, Alice B S et al.", "abstract": "Gulf War Illness (GWI) is a multi-symptom chronic condition that affects Veterans who served in the 1990-1991 Gulf War (GW). To generate novel information about GWI pathogenesis, we used genome-wide data available from 33 523 Veterans of diverse ancestral backgrounds who served during the 1990-1991 Gulf War era (34% deployed). Polygenic score (PGS) analysis showed GWI pleiotropy for several traits with the strongest evidence for type-2 diabetes (T2D), anxiety, and depression. While T2D PGS was associated with higher GWI odds in GW Veterans, anxiety and depression PGSs were associated with higher odds of GWI in non-deployed GW-era Veterans. Seven independent variants were identified (P < 5 × 10-8). Two of them were supported by independent transcriptomic and phenome-wide analyses. Rs4675853 was associated with AGXT, MAB21L4, and ATG4Btranscriptomic regulation and with sex hormone-binding globulin levels. Rs138168412 was associated with AOPEPtranscriptomic regulation and with respiratory function and physical strength. The TWAS identified five additional loci such as CEMIPin the cerebellum and SNCGin the adrenal gland. The results provide a comprehensive assessment of the polygenic architecture of GWI research definitions, identifying mechanisms potentially relevant to the disease pathogenesis.", "url": "https://pubmed.ncbi.nlm.nih.gov/40366759/" }, { "pmid": "40341359", "title": "Persistent enteric neuroinflammation chronically impairs colonic motility in a pyridostigmine bromide-induced mouse model of Gulf War illness.", "pub_date": "2025-05-09", "journal": "Biology open", "authors": "Collier, Claudia A, Salikhova, Aelita, Sabir, Sufiyan, Raghavan, Shreya A", "abstract": "Neuroplasticity in the adult colon enables the enteric nervous system (ENS) to adaptively remodel in response to acute inflammation, preserving motility. However, chronic inflammation may drive maladaptive neuroplasticity, resulting in gastrointestinal dysmotility, a hallmark of functional gastrointestinal disorders, including Gulf War illness (GWI). GWI affects ∼30% of Gulf War veterans and has been linked to oral toxic exposures during combat, such as pyridostigmine bromide (PB). To explore mechanisms of persistent dysmotility, we developed a PB exposure model relevant to GWI. In the colon, we observed structural and functional ENS changes, including an imbalance in excitatory and inhibitory motor neurons and altered motility patterns. These were accompanied by a sustained influx of pro-inflammatory macrophages and elevated cytokine levels, indicating persistent low-grade enteric neuroinflammation. Inflammatory macrophages were found near enteric neural stem cells (ENSCs), impairing their regenerative potential. Transcriptomic analyses corroborated the presence of chronic neuroinflammation and dysregulated repair pathways. Together, our findings suggest that persistent enteric neuroinflammation and impaired neurogenesis contribute to long-term colonic dysmotility in GWI. This model offers new insights into chronic ENS dysfunction and may guide therapeutic strategies for GWI and related disorders.", "url": "https://pubmed.ncbi.nlm.nih.gov/40341359/" }, { "pmid": "40340723", "title": "Navigating Psychiatric Concerns in a Veteran Reporting Gulf War Illness: A Case Report.", "pub_date": "2025-05-09", "journal": "The Permanente journal", "authors": "Botz-Zapp, Christian Alan, Wang, Jami, Kazangian, Eric, Ferrer, Jennifer", "abstract": "Gulf War illness (GWI) is a chronic condition affecting nearly a third of Gulf War veterans and is characterized by persistent symptoms across a number of physical and neuropsychiatric domains. This case study examined a 52-year-old veteran admitted on a psychiatric hold for danger to others. The patient's symptoms, including chronic migraine, widespread musculoskeletal pain, skin sensitivities, environmental allergies, and mood and cognitive disturbances, met criteria for GWI according to 2 accepted case definitions. Initial misdiagnosis of psychosis was corrected upon evaluation, which identified severe anxiety consistent with generalized anxiety disorder. Treatment focused on providing validation of the patient's chronic symptoms and managing his anxiety through pharmacologic intervention. This case underscored the importance of recognizing GWI to ensure accurate diagnoses and targeted care for veterans.", "url": "https://pubmed.ncbi.nlm.nih.gov/40340723/" }, { "pmid": "40332133", "title": "Gulf War Illness Induced Sex-Specific Transcriptional Differences Under Stressful Conditions.", "pub_date": "2025-05-07", "journal": "International journal of molecular sciences", "authors": "Frank, Joshua, Tehrani, Lily, Gamer, Jackson, Van Booven, Derek J et al.", "abstract": "Gulf War Illness (GWI) is a multi-symptom disorder affecting 1990-1991 Persian Gulf War veterans and is characterized by post-exertional malaise, neurological symptoms, immune deregulation, and exhaustion. Causation is not understood, and effective diagnostics and therapies have not yet been developed. In this work, we analyzed stress-related, sex-specific transcriptomic shifts in GWI subjects and healthy controls through RNA sequencing of peripheral blood mononuclear cells (PBMCs). Blood samples at baseline (T0), at maximal exertion (T1), and four hours post-exertion (T2) were analyzed. In female subjects with GWI, pathways associated with pro-inflammatory processes were found to be deregulated, and in male GWI subjects, pathways related to IL-12 signaling and lymphocytic activation were deregulated at T1 compared to T0. During recovery from stress, pathways corresponding to immune responses and microglial cell activation were altered in female GWI subjects, and apoptotic signaling changed in males with GWI. Documented sex-specific immune deregulation leads to finding better biomarkers. Targeting sex-specific transcriptomic markers of the disease could lead to new therapies for GWI.", "url": "https://pubmed.ncbi.nlm.nih.gov/40332133/" }, { "pmid": "40310228", "title": "Ignored, dismissed, and minimized: Understanding the harmful consequences of invalidation in health care-A systematic meta-synthesis of qualitative research.", "pub_date": "2025-05-01", "journal": "Psychological bulletin", "authors": "Bontempo, Allyson C, Bontempo, John M, Duberstein, Paul R", "abstract": "The upsurge in the prevalence of contested, ambiguous, and difficult-to-diagnose illnesses presents challenges for clinicians who too often respond by invalidating patients' symptoms. Although numerous qualitative studies have reported the effects of invalidation on patients' psychological and behavioral outcomes, this body of research has not been systematically reviewed. Informed by Linehan's (1993) conceptualization of invalidation, this systematic review elucidated the negative consequences, of symptom invalidation, or the dismissal or minimization of a person's experiences with illness. We reviewed 151 qualitative reports representing 11,307 individuals with Ehlers-Danlos syndrome, endometriosis, fibromyalgia syndrome, Gulf War syndrome, irritable bowel syndrome, long COVID, multiple chemical sensitivity, myalgic encephalomyelitis/chronic fatigue syndrome, postural orthostatic tachycardia syndrome, systemic lupus erythematosus, and vulvodynia. Consistent with Linehan's theorizing, thematic analysis identified four broad classes of consequences: induced emotional states and beliefs (e.g., shame, suicidality), induced health care emotional states and beliefs (e.g., health care-related anxiety and trauma), induced health care behavior (e.g., health care system avoidance), and diagnostic delay. Informed by these findings, we developed a novel conceptual model explaining how symptom invalidation leads to these consequences and thereby undermines health outcomes. Future work should explore the proposed conceptual model and identify theoretically informed interventions and policies aimed at preventing symptom invalidation to improve psychological, behavioral, and health outcomes. (PsycInfo Database Record (c) 2025 APA, all rights reserved).", "url": "https://pubmed.ncbi.nlm.nih.gov/40310228/" }, { "pmid": "40309656", "title": "16 weeks of moderate intensity resistance exercise improves strength but is insufficient to alter brain structure in Gulf War Veterans with chronic musculoskeletal pain: a randomized controlled trial.", "pub_date": "2025-05-01", "journal": "Frontiers in neuroscience", "authors": "Van Riper, Stephanie M, Ninneman, Jacob V, Stegner, Aaron J, Riedner, Brady A et al.", "abstract": "Chronic widespread musculoskeletal pain (CMP) is a primary condition of Veterans who were deployed to the Persian Gulf War. The mechanisms that underlie CMP in these Veterans are unknown and few efficacious treatment options exist. This study tested the effects of 16 weeks of resistance exercise training (RET) on gray matter (GM) volume and white matter (WM) microstructure in Gulf War Veterans (GWVs) with CMP compared to GWV waitlist controls (WLC). Fifty-four GWVs were randomly assigned to 16 weeks of RET ( Strength increased significantly across the trial for the RET group ( Sixteen weeks of low-to-moderate intensity RET (i) improved musculoskeletal strength and (ii) did not exacerbate symptoms, but (iii) was insufficient to alter brain structure in GWVs with CMP.", "url": "https://pubmed.ncbi.nlm.nih.gov/40309656/" }, { "pmid": "40257120", "title": "US military veterans' perceived concordance with their providers regarding persistent physical symptoms prospectively predicts satisfaction with care and adherence to care plans.", "pub_date": "2025-04-21", "journal": "Annals of behavioral medicine : a publication of the Society of Behavioral Medicine", "authors": "Phillips, L Alison, Lesnewich, Laura M, Bloeser, Katharine, Lin, Yong et al.", "abstract": "Medically unexplained, persistent physical symptoms and syndromes are commonly seen in primary care. These are debilitating for patients and difficult to treat, causing frustration for patients and providers. This study investigates how well US military veterans with multiple persistent physical symptoms (PPS), called Gulf War illness (GWI), agree with their healthcare providers about their illness. This agreement, called perceived concordance, is hypothesized to influence veterans' satisfaction with care, adherence to care plans, and disability levels. Participants were 230 veterans with GWI deployed to the 1990-1991 Gulf War who were recruited from Veteran Affairs primary care and War Related Illness and Injury Study Centers (WRIISCs). Veterans' GWI perceptions and perceived concordance with their providers regarding GWI were assessed at a medical visit. Veterans' self-reported satisfaction with care, adherence to care plans, and disability levels were measured at 1 week, 1 month, and 6 months post-baseline. Bivariate correlations indicated that veterans' GWI-related illness perceptions were related to veterans' satisfaction with care and reports of functional disability. Beyond these effects, veterans' perceived concordance with the provider regarding GWI was positively associated with satisfaction over time (e.g., fixed-effect estimate = 0.36, P < .001 for 1-week follow-up) and adherence to care plans (fixed-effect estimate averaged across all timepoints = 0.03, P = .03) but was unrelated to reported disability. Veterans' perceived concordance with their providers about GWI seems to be important for patient satisfaction and adherence to care plans. More research with longer-term follow-up is needed to understand how perceived concordance might influence disability levels and the outcome of care plans. Chronic conditions that are characterized by persistent physical symptoms and often referred to as “medically unexplained” can be debilitating and difficult to treat. Previous research has found that patients’ perceptions of their conditions (e.g., how severe the symptoms are, what caused the condition) and the degree to which they perceive agreement, called concordance, with their medical provider regarding the condition, predict their subsequent adherence to treatments and experience of symptoms. The current study investigated 230 US military veterans’ perceptions of their Gulf War illness (GWI, considered a “medically unexplained” condition with persistent physical symptoms) and the degree to which they perceived concordance with their provider on their GWI (e.g., on the causes, associated symptoms, and treatment). We found support for the hypothesis that higher levels of perceived concordance at the time of a medical visit would predict greater veteran satisfaction with care and adherence to GWI care plans within the 6 months following a medical visit with the provider. Veterans’ perceived concordance with their providers about GWI seems to be important for patient satisfaction and adherence to care plans, but more research is needed to understand how perceived concordance might influence disability levels and the outcomes of care plans.", "url": "https://pubmed.ncbi.nlm.nih.gov/40257120/" }, { "pmid": "40238573", "title": "The Impact of Home Interventions on Dry Eye Disease (DED) Symptoms and Signs in United States Veterans.", "pub_date": "2025-04-16", "journal": "International journal of environmental research and public health", "authors": "Baeza, Drew C, Penso, Johnathon Z, Menendez, Dhariyat M, Contreras, Julio A et al.", "abstract": "The indoor environment can contribute to dry eye disease (DED) risk, but the effects of environmental modifications on disease are still uncertain. This study evaluated the effect of home interventions that modify the indoor environment on DED symptoms and sign severity. The prospective study consisted of two visits (6 ± 1 months apart). At each home visit, indoor environmental conditions (temperature, humidity, and airborne particulate matter) were monitored and at each clinical visit, DED symptoms and signs were examined. After the first visit, all participants received a report of their home air quality and 10 recommendations to improve their home environment. At the 6-month visit, participants indicated which interventions they implemented. A total of 99 subjects participated in the clinical evaluation and home monitoring at baseline and six-month follow-up. Their mean age was 61 years, and 26% identified as Hispanic. Most had mild or greater DED symptoms (5-Item Dry Eye Questionnaire, DEQ5 ≥ 6), with an average DEQ5 score of 10.49 ± 5.51 at baseline. In total, 77% (n = 76) implemented ≥1 intervention with home ventilation (42.4%), air conditioner filter change (36.4%), and exhaust fan use (31.3%) being the most frequent. Overall, with every intervention implemented, tear osmolarity (change from baseline to 6 months) declined by 2% (log-transformed β = 0.02; 95% confidence interval (CI) = 0.00-0.03; When provided with an objective report of home environmental conditions and remediation strategies, most participants voluntarily implemented low-cost home interventions, which reduced the severity of select DED symptoms and signs.", "url": "https://pubmed.ncbi.nlm.nih.gov/40238573/" }, { "pmid": "40233032", "title": "Retraction: Gulf war illness inflammation reduction trial: A phase 2 randomized controlled trial of low-dose prednisone chronotherapy, effects on health-related quality of life.", "pub_date": "2025-04-15", "journal": "PloS one", "authors": "Authors not listed", "abstract": "No abstract available.", "url": "https://pubmed.ncbi.nlm.nih.gov/40233032/" }, { "pmid": "40222562", "title": "Human leukocyte antigen (HLA) class I and II genetic relationships with brain imaging measures: A systematic review and meta-analysis.", "pub_date": "2025-04-14", "journal": "Brain, behavior, and immunity", "authors": "Zhang, Lusi, Yang, Chengmin, Zhang, Wenjing, Lui, Su et al.", "abstract": "This systematic review and meta-analysis synthesizes current evidence on associations between genetic polymorphisms of human leukocyte antigen (HLA) class I and II molecules, which play key roles in antigen presentation and immune response regulation, and brain imaging phenotypes across various neurological and psychiatric conditions. The strongest associations were observed in multiple sclerosis (MS), where HLA-DRB1*15:01 was linked to increased lesion volume and disease progression. Meta-analyses revealed significant pooled effect sizes for both T1 and T2 lesion volumes. Emerging evidence also suggests that variants in HLA class I and II genes contribute to brain structural changes associated with age-related cognitive decline, schizophrenia, and Gulf War illness. Our findings revealed stronger patterns of association between HLA class II polymorphisms with brain imaging implications as compared to class I in neurodegenerative conditions. Considering HLA class II roles in exogenous protein/peptide presentation, this highlights the potential importance of neuroimmune-environmental interactions as contributing factors to disease pathogenesis and progression. Population-based studies from the UK Biobank highlight the potential influence of HLA class I and II genetic polymorphisms on brain structure beyond disease-specific contexts, suggesting broader implications for neurodevelopment and neurodegeneration. Despite these emerging insights, the limited availability of studies using imaging modalities beyond structural MRI, along with inconsistent findings within specific diseases and across conditions, underscores the need for further investigation into the mechanistic contributions of specific genetic variants on impacting brain structural and functional outcomes. Future research should include larger, more diverse study cohorts and employ advanced genotyping technologies to provide a more comprehensive investigations of HLA's role on brain health across the lifespan.", "url": "https://pubmed.ncbi.nlm.nih.gov/40222562/" }, { "pmid": "40129725", "title": "Dysregulation of lipid metabolism, energy production, and oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome, Gulf War Syndrome and fibromyalgia.", "pub_date": "2025-03-25", "journal": "Frontiers in neuroscience", "authors": "Davis, Leah, Higgs, Maisy, Snaith, Ailsa, Lodge, Tiffany A et al.", "abstract": "Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Gulf War Syndrome (GWS), and Fibromyalgia (FM) are complex, chronic illnesses with overlapping clinical features. Symptoms that are reported across these conditions include post-exertional malaise (PEM), fatigue, and pain, yet the etiology of these illnesses remains largely unknown. Diagnosis is challenging in patients with these conditions as definitive biomarkers are lacking; patients are required to meet clinical criteria and often undergo lengthy testing to exclude other conditions, a process that is often prolonged, costly, and burdensome for patients. The identification of reliable validated biomarkers could facilitate earlier and more accurate diagnosis and drive the development of targeted pharmacological therapies that might address the underlying pathophysiology of these diseases. Major driving forces for biomarker identification are the advancing fields of metabolomics and proteomics that allow for comprehensive characterization of metabolites and proteins in biological specimens. Recent technological developments in these areas enable high-throughput analysis of thousands of metabolites and proteins from a variety of biological samples and model systems, that provides a powerful approach to unraveling the metabolic phenotypes associated with these complex diseases. Emerging evidence suggests that ME/CFS, GWS, and FM are all characterized by disturbances in metabolic pathways, particularly those related to energy production, lipid metabolism, and oxidative stress. Altered levels of key metabolites in these pathways have been reported in studies highlighting potential common biochemical abnormalities. The precise mechanisms driving altered metabolic pathways in ME/CFS, GWS, and FM remain to be elucidated; however, the elevated oxidative stress observed across these illnesses may contribute to symptoms and offer a potential target for therapeutic intervention. Investigating the mechanisms, and their role in the disease process, could provide insights into disease pathogenesis and reveal novel treatment targets. As such, comprehensive metabolomic and proteomic analyses are crucial for advancing the understanding of these conditions in-order to identify both common, and unique, metabolic alterations that could serve as diagnostic markers or therapeutic targets.", "url": "https://pubmed.ncbi.nlm.nih.gov/40129725/" }, { "pmid": "40117126", "title": "Gulf War Illness: A Historical Review and Considerations of a Post-Viral Syndrome.", "pub_date": "2025-03-21", "journal": "Military medicine", "authors": "Bast, Elizabeth, Jester, Dylan J, Palacio, Ana, Krengel, Maxine et al.", "abstract": "Gulf War Illness (GWI) is a condition that affects 30-40% of nearly 700,000 Veterans who were deployed to Operations Desert Shield/Storm/Sabre (ODS/S/S) between August 1990 and June 1991 and is characterized by a constellation of symptoms, including fatigue, mood/cognition, chronic pain, gastrointestinal (most frequently referred to as \"irritable bowel syndrome\"), respiratory, and skin issues. We review the development of various case definitions for GWI, as well as exposure theories. Despite heavy investment in research, both the pathophysiology and underlying cause of GWI remain areas of active inquiry. Similarities have previously been noted in symptomatology between GWI and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and more recently, long COVID (LC), a late effect of infection with the Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2). These conditions are discussed with respect to the similarities of their symptomatology and pathophysiology. Long COVID is a post-viral syndrome, and ME/CFS is widely considered to be likely post-infectious as well. This comparison leads to the proposal of the hypothesis that GWI may also be post-viral. Given the similarity of GWI and LC, it is possible that Veterans with GWI had an antecedent infection with a virus related to SARS-CoV-2, potentially the Middle East Respiratory Syndrome Coronavirus (MERS) or an ancestor of this virus. The MERS antibodies have been found in dromedary camels in Saudi Arabia since 1983 to the present, including the time of ODS/S/S. There is abundant evidence to support further investigation into this topic.", "url": "https://pubmed.ncbi.nlm.nih.gov/40117126/" }, { "pmid": "40068130", "title": "Influence of Adipose Tissue on Ocular Inflammation.", "pub_date": "2025-03-12", "journal": "Cornea", "authors": "Barthelemy, Normila, Goldhardt, Raquel, Cabrera, Kimberly, Galor, Anat", "abstract": "We present a case of ocular pathology linked to morbid obesity, emphasizing the role of systemic inflammation in ocular disease and clinical impact of weight loss. We report the case of a 49-year-old man with morbid obesity and obstructive sleep apnea who underwent bilateral corneal transplants secondary to keratoconus. For 4 years, he had chronic bulbar hyperemia with progressive blood vessel growth across the graft-host junction, which was treated with chronic topical corticosteroids. Nine years after presentation, he also developed severe papilledema associated with idiopathic intracranial hypertension that proved recalcitrant to treatment with acetazolamide therapy and optic sheath fenestration. Concomitantly, the patient's proinflammatory markers (erythrocyte sedimentation rate, C-reactive protein) were consistently elevated. The patient underwent vertical sleeve gastrectomy, resulting in substantial weight loss. Clinical findings, treatment interventions, and outcomes were documented.Results: The patient experienced marked improvement in corneal graft health and resolution of papilledema following weight loss of 188 pounds. Systemic inflammatory markers, including erythrocyte sedimentation rate and C-reactive protein, also normalized. These findings suggest a correlation between adipose tissue mass and ocular inflammation. Our patient had rapid improvements in his ocular pathology that correlated with a notable reduction in body fat percentage. We propose that the immunological changes associated with obesity contributed to a proinflammatory ocular state that improved with weight loss. His case highlights that additional research is warranted to explore the etiopathogenic mechanisms of adipokines derived from white adipose tissue on major organ systems, including the eye.", "url": "https://pubmed.ncbi.nlm.nih.gov/40068130/" }, { "pmid": "40020650", "title": "The association between Gulf War Illness and suicidal thoughts and behaviors among Gulf War Era Veterans.", "pub_date": "2025-03-01", "journal": "Journal of psychiatric research", "authors": "Lipsky, Rachele K, Helmer, Drew A, Beckham, Jean C, Calhoun, Patrick S et al.", "abstract": "The rate of death by suicide is elevated among Veterans of all eras. Chronic symptoms of pain, depression, and sleep disturbances are also common among Veterans, and these symptoms are associated with suicidal thoughts and behaviors. About 25% of the 697,000 Gulf War Era Veterans deployed to the Persian Gulf theater in 1990-1991 remain afflicted with chronic, unexplained symptoms known as Gulf War Illness (GWI). This study used data from a national sample of Gulf War Veterans (N = 1142) who completed a survey of demographic, military, and health information. Multivariable logistic regression models, controlling for confounding variables, tested for associations between deployment, a tri-level categorical variable of GWI (no GWI; moderate GWI; and severe GWI) and suicidal thoughts and behaviors. Deployment was not associated with any suicide related outcome. Moderate and severe GWI remained significantly associated with past year suicidal ideation (moderate GWI: aOR 3.94; 95% CI: 1.55-10.03; severe GWI: aOR 3.66; 95% CI: 1.31-10.20), but they were not associated with suicide attempts. Our findings suggest that the burden and negative impact of the chronic symptoms of GWI may play a role in the occurrence of suicidal ideation in Gulf War Veterans (GWV). Clinicians caring for GWVs should attend to both chronic symptoms, and the elevated risk of suicidal thoughts in this cohort.", "url": "https://pubmed.ncbi.nlm.nih.gov/40020650/" }, { "pmid": "40014289", "title": "The role of the working alliance in improving outcomes among veterans with Gulf War Illness: a longitudinal study.", "pub_date": "2025-02-27", "journal": "Journal of behavioral medicine", "authors": "Gentile, Anna M, Rogers, Caroline O, Lesnewich, Laura M, Lu, Shou-En et al.", "abstract": "Military Veterans with Gulf War Illness (GWI), a \"medically unexplained\" persistent physical syndrome (PPS), have difficult experiences of care, in part, due to non-concordant relationships with their healthcare providers. A critical factor in improving care for this population may be the working alliance, which is the extent to which patients and providers agree on the goals and tasks of treatment and have a shared bond. The present study examined if, for Veterans with GWI, perceptions of the working alliance over time predicted better experiences of care (i.e., patient satisfaction and treatment adherence) and improved health outcomes (i.e., reduced disability, depression symptoms, and physical symptoms). Positive Veteran perceptions of the working alliance at 4 weeks were related to better patient satisfaction and treatment adherence at 12 weeks. Veteran perceptions of the working alliance were not consistently related to reductions in disability, depression symptoms, or physical symptoms. The results of this study suggest that the working alliance is important for improving patient experiences of care but may not be sufficient to consistently impact health outcomes.", "url": "https://pubmed.ncbi.nlm.nih.gov/40014289/" }, { "pmid": "39958343", "title": "Corrigendum: Brain-specific increase in leukotriene signaling accompanies chronic neuroinflammation and cognitive impairment in a model of Gulf War Illness.", "pub_date": "2025-02-17", "journal": "Frontiers in immunology", "authors": "Attaluri, Sahithi, Upadhya, Raghavendra, Kodali, Maheedhar, Madhu, Leelavathi N et al.", "abstract": "[This corrects the article DOI: 10.3389/fimmu.2022.853000.].", "url": "https://pubmed.ncbi.nlm.nih.gov/39958343/" }, { "pmid": "39860380", "title": "Localization of Microvascular Changes in Systemic Disease Without Retinopathy Using Optical Coherence Tomography Angiography (OCTA).", "pub_date": "2025-01-25", "journal": "Journal of clinical medicine", "authors": "Hattenhauer, Alex, Cabrera, Kimberly, Locatelli, Elyana V T, Donthineni, Pragnya Rao et al.", "abstract": "No abstract available.", "url": "https://pubmed.ncbi.nlm.nih.gov/39860380/" }, { "pmid": "39852867", "title": "Negative Association of Gulf War Illness Symptomatology with Predicted Binding Affinity of Anthrax Vaccine Antigen to Human Leukocyte (HLA) Class II Molecules.", "pub_date": "2025-01-24", "journal": "Vaccines", "authors": "James, Lisa M, Georgopoulos, Apostolos P", "abstract": "Anthrax is a serious disease caused by Here, we tested this hypothesis by determining the association between severity of GWI symptoms in 458 GW veterans and the overall strength of the binding affinity of the PA epitopes to the specific six Human Leukocyte Antigen (HLA) Class II alleles carried by each individual (two of each of the HLA-II genes: DPB1, DQB1, DRB1), responsible for initiating the process of antibody production in otherwise immunocompetent individuals, estimated in silico. We found that the severity of GWI symptomatology was negatively and significantly correlated with the strength of the predicted binding affinity of PA peptides to HLA-II molecules (r=-0.356, p<0.001); the stronger the overall binding affinity, the weaker the symptoms. Since the binding of a peptide to an HLA-II molecule is the first and necessary step in initiating the production of antibodies, the findings above support our hypothesis that the severity of GWI symptomatology is partly due to a lack of HLA-II protection. Reduced HLA protection against the toxic anthrax vaccine may underlie GWI.", "url": "https://pubmed.ncbi.nlm.nih.gov/39852867/" }, { "pmid": "39825183", "title": "\"They Make It So Hard on You\": How Rurality Shapes Veterans' Health Experiences When Managing Gulf War Illness.", "pub_date": "2025-01-18", "journal": "Journal of general internal medicine", "authors": "Jespersen, Brooke V, Lafferty, Megan, Montague, Kara, Ono, Sarah et al.", "abstract": "Gulf War illness (GWI) is characterized by multiple, persistent symptoms (e.g., fatigue, musculoskeletal pain, concentration problems, and gastrointestinal disorders) across more than one body system that are severe enough to interfere with daily functioning. For Veterans in rural areas, the confluence of geographic barriers and GWI may create unique challenges when navigating health care, given the range of specialty care needed to support GWI. However, little is known about how rural Veterans manage their GWI symptoms and navigate health care systems. To examine how Veterans with GWI perceive rurality to influence their health care experiences. A cross-sectional qualitative study utilizing Health Experiences Research methodology. Veterans with GWI, who served in the active-duty US military, National Guard, or Reserves during the 1990-1991 Gulf War (GW) and who connected rurality to their health care experiences during interviews. Secondary qualitative analysis and inductive thematic analysis of semi-structured interviews, conducted between November 2018 and August 2021, with Veterans about their military and health experiences over time. Fifteen (n = 15) Veterans with GWI connected rurality to their health care experiences and quality of life. Three themes emerged from their interviews: (1) GWI and rural residence amplified problems with care coordination; (2) Managing GWI made distance especially burdensome; and (3) Rural contexts facilitated wellness and support, while creating barriers to accessing care. Our findings suggest that rurality intersects with GWI management in ways that compound barriers to health care access for Veterans. VA can address time and distance barriers by continuing to expand specialty telehealth services and telehealth training for providers and patients. VA could also incorporate recommendations from the VA/DoD clinical practice guidelines into point-of-care decision support to enhance recognition of GWI and improve consistency of treatment, which may contribute to trust-building among GW Veterans.", "url": "https://pubmed.ncbi.nlm.nih.gov/39825183/" } ] }