The Geisel School of Medicine is the medical school of Dartmouth College, an Ivy League research university located in Hanover, New Hampshire, United States. The fourth-oldest medical school in the United States, it was founded in 1797 by New England physician Nathan Smith and grew steadily over the course of the 19th century. Several milestones in medical care and research have taken place at Dartmouth, including the first clinical X-ray (1896), the first intensive care unit in the United States (1955), and the Brattleboro rat (1961).Today, Dartmouth's Geisel School of Medicine continues to grant the Doctor of Medicine (M.D.) and Doctor of Philosophy (Ph.D.) degrees, as well as a Master of Public Health (M.P.H.) and Master of Science (M.S.) degrees. The school has a student body of about 700 students and more than 2,300 faculty members and researchers. Geisel organizes research through over a dozen research centers and institutes, receiving more than $140 million in grants annually. The Geisel School of Medicine is one of seven Ivy League medical schools and is ranked as a "top medical school" by U.S. News & World Report for both primary care and biomedical research. Dartmouth's medical school has numerous clinical partners, including Dartmouth-Hitchcock Medical Center, White River Junction Veterans Administration Medical Center, California Pacific Medical Center, and Manchester Veterans Administration Medical Center.
Low-level blast (LLB) exposures generated by weapons systems and explosives use are now recognized as an occupational hazard for many military and law-enforcement communities. Although individual exposures often fall below thresholds for clinically diagnosable concussion, accumulating data from human and animal studies suggest that repetitive LLB can produce subtle but durable changes in neurobehavioral function, neuroimaging markers, and blood- and CSF-based biomarkers, as well as cardiovascular and neurovascular health. At the same time, the field remains fragmented, with heterogeneous exposure metrics, characterized by non-standardized exposure quantification methods, variable outcome measures, and inconsistent longitudinal follow-up intervals. This state-of-the-science review synthesizes current evidence on LLB with a deliberate emphasis on clinical aspects that matter to Servicemembers, Veterans, and clinicians focusing on posttraumatic outcomes (e.g., psychological, cognitive, physical), reduction of risk of neurodegenerative disease, and practical pathways for exposure prevention and mitigation. We first describe contemporary definitions and patterns of LLB exposure across operational communities, followed by a critical appraisal of epidemiological studies linking LLB to symptoms, functional outcomes, and health-care utilization. We then summarize converging evidence for neurodegenerative and neurovascular risks, integrate mechanistic insights from neuroimaging, neuropathology, and animal models, and highlight emerging biomarker and computational approaches. Finally, we outline pragmatic strategies for exposure assessment, screening, and follow-up in clinical settings and identify high-priority research and policy directions. Rather than asking whether LLB is "safe" or "unsafe" in absolute terms, we focus on vulnerability and context as a roadmap for scientific and clinical development while balancing mission requirements with long-term brain health.
Pseudomonas aeruginosa is an important agent of acute or chronic airway infections. A complex set of genetic and environmental factors determine the outcome of a P. aeruginosa airway infection. P. aeruginosa can undergo genetic adaptation to fine tune the expression of a type III secretion system (T3SS) and other virulence factors in response to selective pressures encountered during infection. Genetic and environmental factors predispose many patient groups for P. aeruginosa infections, including people with cystic fibrosis (pwCF). CF is a genetic disorder resulting in areas of hypoxia and thick mucus that fosters P. aeruginosa airway infection. Resident alveolar macrophages (AMs) help coordinate immune responses to P. aeruginosa in airways by producing proinflammatory cytokines such as IL-1β, which can be important for infection resistance. AMs infected with laboratory strains of P. aeruginosa detect the T3SS and activate the NLRC4 inflammasome, resulting in IL-1β release. Studies of inflammasome responses in AMs to a clinical CF isolate of P. aeruginosa have not been reported. Here, we characterized the CF clinical isolate DH1137 and found that it has a downregulated but functional T3SS, is adapted to grow in hypoxia, and induces significant production of the inflammasome cytokines IL-1a and IL-1β during lung infection in a CF mouse model. Inflammasome gene expression was primed in AMs by LPS stimulation, and upon DH1137 infection these cells released IL-1β. Intriguingly, we found that infection of AMs with DH1137 in hypoxia resulted in significantly dampened inflammasome activation compared to normoxia. These data describe a new mechanism that P. aeruginosa may exploit to evade immune detection by tissue-resident lung macrophages in the context of CF. ### Competing Interest Statement The authors have declared no competing interest. National Institutes of Health, https://ror.org/01cwqze88, T32HL134598 Cystic Fibrosis Foundation, BLISKA24I0 The Philip Hanlon and Gail Gentes Cluster for Personalized Treatments for Cystic Fibrosis
Objective To characterize the prevalence, severity, and clinical correlates of subjective ictal-phase cognitive impairment across the migraine attack cycle in a large, specialty-center cohort. Background Cognitive dysfunction is a prevalent and disabling feature of migraine attacks, yet standardized tools for measuring migraine attack-related cognitive impairment are limited, and the clinical predictors of cognitive burden remain incompletely characterized. Prior work has largely focused on the ictal phase, although cognitive symptoms are reported across the prodromal, ictal, and postdromal phases of the migraine attack. Methods This is a cross-sectional analysis of data from the American Registry for Migraine Research (ARMR), a multicenter registry enrolling patients with migraine diagnosed by headache specialists using ICHD-3 criteria. Participants completed the Migraine-Specific Cognitive Impairment Scale (Mig-SCog; range 0–18, higher scores indicating greater impairment). Associations between cognitive impairment and clinical variables were evaluated using correlation analyses, group comparisons, and multivariable linear regression. Results Among 1,231 patients (87.2% women; mean age 46.0 ± 13.7 years; 71.5% chronic migraine), 1,175/1,231 (95.5%) endorsed cognitive symptoms, with a mean Mig-SCog total score of 8.2 ± 4.8. Executive dysfunction accounted for 71.1%±18.6% of total cognitive burden, but the proportional contribution of language impairment increased with migraine frequency category, from 22.4%±18.9% in low-frequency episodic migraine to 28.8%±19.5% in chronic migraine (p = 0.003). In multivariable regression, migraine frequency classification was not independently associated with cognitive impairment. The strongest independent predictors of cognitive impairment were anxiety symptom score (β = 0.15, p < 0.001) and depression symptom score (β = 0.13, p = 0.002), with standardized coefficients exceeding those of all migraine frequency classification categories. Women reported significantly greater cognitive impairment than men across all domains (8.4 ± 4.8 vs. 6.8 ± 4.7; p < 0.001, small effect). Word-finding difficulty demonstrated the largest ictal symptom-frequency association, with scores rising from 3.3 ± 2.6 among those never reporting word-finding difficulty to 13.6 ± 3.6 among those always reporting it (adjusted p < 0.001, large effect). In phase-based analyses, word-finding difficulty and impaired concentration were associated with 4.6- and 3.7-point higher cognitive impairment scores than in patients who did not report these symptoms during the prodrome and 5.1- and 4.0-point higher scores during the postdrome, respectively (all p < 0.001, large effects). Among patients with chronic migraine and available disease duration data (n = 661), cognitive burden was lower among those within the first 12 months of chronicity compared with those with longer-standing chronic migraine (7.7 ± 4.9 vs. 9.0 ± 4.6; p = 0.010, d = 0.27). Sound hypersensitivity (β = 0.25) and cutaneous allodynia (β = 0.20) were the strongest independent sensory predictors of cognitive impairment (both p < 0.001). Conclusion Migraine-related cognitive dysfunction was nearly universal in this specialty-center cohort and was not adequately captured by migraine frequency classification alone. Anxiety and depression symptom burden, language impairment, full-cycle cognitive symptoms spanning prodrome through postdrome, and sensory sensitization are clinically meaningful markers of cognitive burden that should be assessed alongside more traditional migraine characteristics when evaluating patients who have migraine.
Vicarious trauma-witnessing serious harm to others-produces systemic neuroimmune effects in animal models. However, its brain, autonomic, and immune consequences in humans remain unclear. We scanned 88 participants with fMRI during a naturalistic movie-viewing paradigm depicting either industrial cruelty to farm animals (Vicarious Trauma, VT) or positive human-animal interactions (Vicarious Community, VC) with concurrent autonomic physiology and gene expression in circulating monocytes. VT, compared to VC, evoked sustained sympathetic arousal lasting 40 minutes post-viewing and primed innate immune cells to elicit elevated pro-inflammatory (upregulating IL1B and CXCL8) and reduced anti-inflammatory (TGFB1) responses. VT reduced integration in a frontoparietal control system and increased coupling between a salience/action-mode system with paralimbic, basal ganglia, and sensorimotor regions. Disrupted negative coupling between frontoparietal/default-mode and hippocampal systems predicted VT-related CXCL8 increases. These findings shed light on how the brain translates vicarious trauma into the priming of innate immunity.
