Emory and Henry College

Increasing research efforts in recent years and new approaches in clinical studies provided significant insights into the pathophysiology of freezing of gait (FOG). However, the study of causative mechanisms for complex gait disorders typically needs refined in-vivo models, which are still lacking for FOG. The characteristics of FOG pose major difficulties not only for reproduction in animals with different types of gaits, but also for assessment of such episodic behavior in the animal environment. In this review, we examine the currently available animal models of FOG and FOG-like phenomena for their validity and applicability and present a prospective view of modeling based on novel technologies to manipulate integrated mechanisms.

Abstract Background Peripheral artery disease (PAD) and chronic limb-threatening ischemia (CLTI) cause substantial morbidity and mortality, yet research progress is limited by fragmented, non-standardized data. The Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) provides a standardized framework for electronic health record (EHR) research but lacks domain-specific detail for peripheral vascular diseases. This study aimed to develop and test a vascular-specific OMOP CDM extension to improve data standardization, enable reproducible real-world analyses, and support precision medicine research in PAD and CLTI. Methods We identified patients with PAD, CLTI, or diabetic foot ulcers who sought care within the UNC Health System between April 2014 and July 2024. Standard OMOP tables were supplemented with peripheral vascular laboratory (PVL) data and state death records. Intermediate tables were designed for key clinical domains (e.g., smoking, comorbidities, revascularizations) to enhance reusability. Predictive models for revascularization and mortality were developed using logistic regression with Bayesian weighting and Markov Chain Monte Carlo feature selection. Clinical Application The revascularization model displayed high performance with and without important vascular variables (AUC = 0.970 and AUC 0.969, respectively), while the mortality model demonstrated moderate accuracy (AUC = 0.656) that improved with inclusion of vascular-specific features (AUC = 0.752). Conclusions This vascular OMOP extension represents one of the first specialty-specific frameworks for peripheral vascular research. By extending the OMOP CDM to a vascular domain, this work advances both the technical framework and scientific capability of real-world data research in limb preservation and precision vascular medicine.

CD4 T cells are essential for immunity to M tuberculosis (Mtb), and emerging evidence indicates that IL-17-producing Th17 cells contribute to immunity to Mtb. While identifying protective T cell effector functions is important for TB vaccine design, T cell antigen specificity is also likely to be important. To identify antigens that induce protective immunity, we reasoned that, as in other pathogens, effective immune recognition drives sequence diversity in individual Mtb antigens. We previously identified Mtb genes under evolutionary diversifying selection pressure whose products we term Rare Variable Mtb Antigens (RVMA). Here, in 2 distinct human cohorts with recent exposure to TB, we found that RVMA preferentially induce CD4 T cells that express RoRγt and produce IL-17, in contrast to "classical" Mtb antigens that induce T cells that produce IFN-γ. Together with emerging evidence showing human Th17 responses are associated with prevention of progression to TB disease, our results suggest that RVMA can be valuable antigens in vaccines for those already infected with Mtb to amplify existing antigen-specific Th17 responses to prevent TB disease.

BackgroundInterferon gamma release assays (IGRAs) are a preferred method of screening for latent tuberculosis infection (LTBI). Recently, a fully automatic chemiluminescence immunoassay (CLIA) became available in the United States with the promise of improving lab workflow. Initial evaluations of this assay have suggested low reproducibility and increased positive results relative to the prior standard of enzyme-linked immunosorbent assays (ELISA). We aimed to characterize the impact of CLIA implementation on our health system.Table 1MethodsWe conducted a retrospective chart review of all IGRAs conducted at Grady Health System from 1/1/2021 to 3/31/2025 (CLIA implemented on 5/13/2023). We compared the rate of test positivity (TB1 - nil or TB2 - nil >=0.34), borderline positivity (TB1 – nil or TB2 – nil 0.34=< x < 1.0 and neither >=1.0), and non-borderline positivity (positive but not borderline positive) before and after CLIA implementation using the two-proportion z test. An interrupted time series (ITS) analysis using a quasi-Poisson regression model was used to analyze the testing change. For patients with multiple tests, we calculated the rate of seroconversion and the impact on patient management.Results22392 IGRAs were performed during the study period (Table 1). Positivity rate (6.7% vs 5.4%; p < 0.001) and borderline positivity (2.5% vs 1.6%; p < 0.001) were higher for CLIA than ELISA. Non-borderline positive results were not significantly different. In ITS analysis (Figure 1), CLIA implementation was associated with a significant level change in the borderline positivity rate but not the nonborderline positivity rate. Of 1928 instances of repeat IGRA testing, 29 were seroconversions of which 27 were borderline positive. Repeat tests on the CLIA were more likely to be a seroconversion (2.0% vs 0.4%, p = 0.018). 15/27 borderline seroconversions were referred for treatment and 8/27 had a therapy modification (e.g. DMARD interruption).ConclusionCLIA implementation for IGRAs was associated with increased positivity that is explained by increased borderline positive results that are likely false positives. Diagnostic stewardship measures are needed to mitigate the impact of these results and prevent harm from unnecessary LTBI treatment and/or interruptions of chronic disease therapy.DisclosuresEli Wilber, MD, Elsevier: Honoraria|Roche Diagnostics: Honoraria

BackgroundIsolated REM sleep behavior disorder (iRBD) is a parasomnia that reflects an evolving α‐synucleinopathy disorder, providing an opportunity to study early pathological changes. While diffusion tensor imaging (DTI) studies have shown white matter changes in iRBD, Neurite Orientation Dispersion and Density Imaging (NODDI) may offer better biological specificity in characterizing microstructural alterations through measures of Neurite Density Index (NDI), Orientation Dispersion Index (ODI), and Free Water Fraction (FWF).MethodWe included 77 participants with polysomnography‐confirmed iRBD from the North American Prodromal Synucleinopathy (NAPS) Consortium and 154 age‐ and sex‐matched cognitively unimpaired controls from the Mayo Clinic Study of Aging. White matter microstructure was evaluated using standardized multi‐shell diffusion on 3T MRI, quantifying DTI metrics (fractional anisotropy, FA; and mean diffusivity, MD) and NODDI parameters across bilateral white matter tracts defined by the JHU “Eve” WM atlas. Group differences were assessed using conditional logistic regression, with correlations to motor performance evaluated using the Purdue Pegboard and Alternating Finger Tapping tests.ResultCompared to controls, iRBD participants demonstrated widespread and bidirectional white matter changes across major white matter pathways (see Figure 1 for glass brain visualizations). While predominantly showing decreases, FA exhibited some increases, particularly in the corticospinal tract. MD showed a largely opposite pattern with predominantly increased values across tracts. NODDI metrics revealed complex bidirectional patterns: ODI was broadly increased across multiple tracts with focal decreases, while NDI showed a pattern of predominantly decreased values alongside localized increases. FWF demonstrated a mixed pattern with predominant decreases across most tracts. In addition, both DTI and NODDI metrics showed extensive, moderate correlations with the Purdue Pegboard Test and Alternating Finger Tapping performance (T = 2.0, p < 0.05, Figure 2).ConclusionOur study highlighted widespread and complex bidirectional white matter microstructural alterations in individuals with iRBD, demonstrating significant correlations with dexterity and motor performance even during the prodromal stage. These results suggest that extensive white matter abnormalities occur early in prodromal α‐synucleinopathies and highlight the value of advanced diffusion imaging techniques in characterizing iRBD and its potential prediction of phenoconversion to overt neurodegenerative disorders.

BackgroundIn humans, age‐related accumulations of physical deficits are often characterized by frailty indices, which predict increased risk for neurodegeneration characteristic of Alzheimer's disease (AD). However, social capabilities also may diminish, with considerable variation in inter‐individual trajectories of decline and AD risk. Social frailty has recently been proposed in humans and mice to characterize the severity of social impairments with age; however, no index of social frailty exists for nonhuman primates (NHPs). This represents a significant gap in the literature, as NHPs provide important translational opportunities to study brain‐body relationships that promote healthy versus pathological aging.MethodHere, we developed a novel index of social frailty in female vervet monkeys (Chlorocebus aethiops sabaeus) using six components of social behavior measuring positive interactions, agonistic interactions and social isolation. Members of this study comprise the Wake Forest Aging Vervet Cohort, which includes 30+ captive females ranging from middle‐ to very old age (8‐29 years). Subjects live with their families in large, multi‐matrilineal social groups. We first tested whether social frailty in vervets recapitulated age‐related changes observed in humans. Next, we determined the cross‐sectional relationships between social frailty and neuroanatomy derived from structural MRI. Finally, we tested whether social frailty predicted biomarkers associated with AD (MesoScale Discovery Platform: Ab40, Ab42, Ab42:40, ptau181, NfL, and GFAP) in CSF at approximately one year follow‐up.ResultThe social frailty index increased with age (t= 3.695, p <0.001). Social frailty was positively associated with CSF volumes (t= 2.163 p = 0.035) and negatively associated with cortical gray matter (t=‐4.261, p <0.001), white matter (t=‐2.591, p = 0.013), and cerebellar (t=‐3.716, p <0.001) volumes. Social frailty also predicted several CSF biomarkers associated with AD. Higer social frailty predicted higher levels of phosphorylated tau (t=2.304, p = 0.024) but lower Ab42 (t=‐2.345 p = 0.022) and Ab40 (t=‐2.138, p = 0.036). Social frailty was also associated with elevated NfL and GFAP in CSF; however, the associations did not reach statistical significance (p's <0.10).ConclusionLike humans, some vervets may exhibit increasing socially frailty with age. These unhealthy aging trajectories ‐ characterized by fewer positive interactions, social isolation, and agonistic interactions ‐ are associated with AD neuroimaging and biofluid biomarkers.

ABSTRACTBackgroundPost‐embolization syndrome after transarterial chemoembolization (TACE) and Yttrium‐90 radioembolization (TARE) causes significant morbidity. Understanding whether discharge prescriptions influence short‐term outcomes may guide standardized pain‐management strategies.MethodsA retrospective cohort study of 3191 patients (3988 procedures) with hepatocellular carcinoma from the Merative MarketScan Databases (2009–2022) was performed. The composite outcome was 7‐day drug escalation or hospital readmission. Bivariate logistic regression identified candidate variables (p < 0.10); multivariable logistic regression with patient‐clustered robust standard errors estimated adjusted odds ratios (aORs), adjusting for age, sex, and Charlson Comorbidity Index (CCI).ResultsCompared to patients discharged without opioids post‐chemoembolization, those prescribed opioids at discharge had 83% lower odds of experiencing drug escalation or readmission (odds ratio [aOR] = 0.17, p < 0.001), and those undergoing radioembolization had 59% lower odds (aOR = 0.41, p < 0.001). Being prescribed antiemetics or steroids was also associated with lower odds of escalation/readmission events, with percentages varying by procedure type.ConclusionsPrescribing opioids, along with antiemetics and steroids, at discharge may reduce the likelihood of post‐procedural events, such as drug escalation and readmission, in patients undergoing trans‐arterial chemoembolization and radioembolization for hepatocellular carcinoma. These findings highlight the importance of a comprehensive pain management strategy in interventional oncology and warrant consideration in clinical practice guidelines.