Aging is widely associated with chronic low-grade inflammation and dysregulation of innate immune signaling pathways that contribute to inflammatory processes. In addition, cannabis use is increasing among older populations and little is known about the effects of cannabis use on age-related immune dysfunction. This project aims to explore how active cannabis component Δ-9-tetrahydrocannabinol (THC), alone and in combination with cannabidiol (CBD), affects the immune response in mouse models to determine how additional stimulation of the endocannabinoid system modulates neuroinflammation. We treated adult (~4 month) or aged mice (~2 years) with THC alone, or THC:CBD at 1:1 ratio for 3 weeks. We then analyzed relative expression of inflammatory and stress markers CCL4, C1qa, TREM2, and MX1 using brain tissues. These genes are linked to innate immune responses, including type I Interferon response, and inflammasome response. The results of the qPCR showed that cannabinoid treatment led to aged mice exhibiting higher baseline expression of CCL4, Cq1a and TREM2 compared to adults, while showing mixed results on the expression of all assessed genes. Studies are ongoing to examine the transcriptomic changes in the brain by RNAseq in adult, aged and aged mice with THC, THC/CBD treatment. Overall, this study offers insight into molecular signatures associated with aging and inflammation and the potential of cannabinoids to modulate age related CNS inflammation.

Presbycusis, or age-related hearing loss (ARHL), is associated with cumulative anatomical, cellular, and biochemical changes in the auditory pathway that develop with age and grows increasingly prevalent in the aging population. While previous studies explored various anatomical structures of hearing loss, the spiral ligament largely remained uncharacterized. This periosteal thickening along the lateral cochlear wall contains fibrocytes crucial for maintaining potassium and bicarbonate homeostasis through ion recycling pathways. We hypothesized that aging causes specific fibrocyte damage in the spiral ligament contributing to ARHL. We investigated expression of Slc4a10 (solute carrier family 4, sodium bicarbonate transporter, member 10), or Na+-driven Cl−/HCO3− exchanger (NCBE), which was linked to mouse aging but was largely unstudied in humans. Archival celloidin embedded sections of human temporal bones from mid-age (31–60-year-old) and old-age (61-90+ years old) individuals were studied using indirect immunohistochemistry with primary NCBE antibodies to localize NCBE in the spiral ligament. Digital immunofluorescence images were collected using laser confocal microscopy. NCBE was found in both the mid- and old-age groups in the basal, middle, and apical spiral ligament. However, the basal region showed reduced fluorescence for the old-age group. Decreased NCBE in the basal portion of the spiral ligament in older individuals suggest NCBE may serve as a biomarker for aging and associated ARHL.

Fracture-related infection (FRI) remains a major complication in orthopaedic trauma, particularly in patients with polytrauma. Though polytrauma is known to alter immune responses, its impact on inflammatory signaling and infection burden at the fracture site is not well characterized. To investigate this, a murine model was utilized and animals were randomized into three groups: Polytrauma with aseptic femur fracture, isolated septic femur fracture and polytrauma with septic femur fracture. Polytrauma was induced via blunt thoracic trauma. Bacterial burden, serum cytokine levels and bone healing were assessed in each group. At 72 hours, the septic polytrauma group demonstrated increased and more diffuse bioluminescent signal compared to the isolated septic fracture group. The septic polytrauma group also displayed significantly elevated pro-inflammatory cytokines at both 72 hours and 3 weeks compared the aseptic polytrauma and septic fracture groups, suggesting a sustained and amplified inflammatory response. Despite these findings, micro-computed tomography (μCT) at three weeks revealed no significant differences in structural bone parameters between groups. These findings suggest that systemic immune dysregulation may impair early bacterial clearance without altering the early stages of structural bone healing. Understanding these interactions can inform targeted immunomodulatory or antimicrobial strategies to improve outcomes in polytraumatized patients with fracture-related infection.

Title: Utility of Swept-Source Anterior Segment Optical Coherence Tomography in the Longitudinal Monitoring of HLA-B27-Associated Anterior Uveitis AMBER HENNY, Ali Jaafar Haidar, Alessandro Feo, Shin Kadomoto, Jaiden Huang, Annabelle Tran, Nidhi Thati, Brooke Yasuda, Anthony Wu, Adrian Au, Keren Chen, Nicholas J. Jackson, Edmund Tsui Purpose: To evaluate swept-source anterior segment optical coherence tomography (SS AS-OCT) algorithm for quantifying hyperreflective foci (HRF) as an objective biomarker of anterior chamber (AC) inflammation in a cohort of HLA-B27 anterior uveitis, to assess its relationship with clinical Standardization of Uveitis Nomenclature (SUN) grading, and to characterize longitudinal changes in HRF burden across defined stages of disease activity. Methods: A longitudinal analysis was conducted on 18 eyes from 16 HLA-B27-positive patients with anterior uveitis who underwent swept-source AS-OCT imaging at three clinically defined timepoints: T1 (flare), T1 (quiet/improving), and T2 (quiet). The number of anterior chamber HRF were quantified using a custom automated algorithm. Clinical grading of inflammation was assessed at each visit using the Standardization of Uveitis Nomenclature (SUN) criteria. Same-day clinical exams and SS AS-OCT imaging were performed using a single 14 mm horizontal scan before dilation. Mixed-effects linear regression was used for analysis. Results: The median time between T0 and T1 was 29 days, and between T1 and T2 was 65 days. At T0, SUN grades were 0.5+ in 7/17 eyes (41.2%)

Red blood cell transfusions elicit variable inflammatory responses in critically ill children with multiple organ dysfunction syndrome (MODS), but the mechanisms underlying this variability remain unclear. We used a correlation-based protein-protein interaction network to identify coordinated biomarker responses to transfusion and compared expression between hyper- and hypo-inflammatory latent profiles previously derived from the patients’ baseline inflammatory states. Plasma samples from 146 children were analyzed pre- and post-transfusion using a multiplex biomarker panel, with changes quantified as log2 fold differences from day 0 to day 1. Spearman correlation coefficients were computed for all marker pairs (n=249) and used to identify clusters via hierarchical and k-means clustering. Significant marker relationships (|ρ|>0.5, FDR<0.05) were visualized in Gephi and modularity analysis created clusters. Pathway enrichment was assessed using STRINGdb and a background list of all markers. Differences in the expression of significant clusters between latent profiles were assessed using the Wilcoxon rank-sum test. A cluster (n=29) enriched for the NOD-like receptor pathway (FDR=0.008) consistently appeared across all methods with largely overlapping markers. It showed higher expression in the hyperinflammatory patient group (p=0.047). These findings suggest that the pathway may drive post-transfusion inflammatory responses and can help us understand how to tailor treatments to patients based on their unique immune states.