Neurosciences Commons^™

Development Of A Mediation Model Of Pain Cognition In Adult Patients With Sickle Cell Disease, Daniel M. Sop

Theses and Dissertations

Pain is a hallmark of Sickle Cell Disease (SCD), a genetic hemoglobinopathy characterized by chronic hemolytic anemia, vaso-occlusion, and organ damage. While acute vaso-occlusive crises (VOC) have been extensively studied, the mechanisms underlying chronic pain and its interplay with brain function remain unclear. This dissertation investigates the relationships between cerebral blood flow (CBF), fluid cognition, and pain sensitivity in adults with SCD, utilizing advanced imaging techniques and validated assessment tools.

Arterial spin labeling (ASL) and functional magnetic resonance imaging (fMRI) were employed to measure CBF and brain activity, respectively. Pain sensitivity was assessed using the Pain Sensitivity Questionnaire (PSQ), and …

From Misinformation To Policy Solutions: Teaching Herd Immunity And Vaccine Hesitancy Through Real-World Case Studies Of Measles Outbreaks, Laurieann Klockow

Biomedical Sciences Faculty Research and Publications

Vaccine hesitancy threatens herd immunity, contributing to the resurgence of measles outbreaks. This lesson engages upper-level biomedical science students in analyzing the complex interplay between vaccination rates, herd immunity and vaccine exemption policies through examination of the 2019 New York measles outbreak that threatened the United States’ measles elimination status. Students critically evaluate anti-vaccine misinformation, analyze epidemiological data and develop evidence-based policy recommendations to increase vaccination rates. The lesson combines team-based learning with authentic assessment through vaccine policy development, moving beyond knowledge acquisition and content to building scientific literacy and evidence-based reasoning skills essential for scientifically literate citizens and future …

A Comparison Of Two Motivational Tasks In Male And Female Rats Under Acute Stress, Stephanie M. Muscott

Graduate Research Theses & Dissertations

Motivation is a complex concept that contributes to or is embedded within many different behaviors. As such, it can be difficult to assess motivation directly, but many researchers have attempted to measure motivation to understand its role in behavior and in diseases associated with a dysregulation of motivation, such as drug addiction or depression. To better understand motivation, behavioral tests frequently use palatable foods to measure motivation as defined by the amount of effort a rat will demonstrate to achieve the reward. Much of research has focused on highly controlled experimental settings, such as lever pressing in an operant box …

Synthesis And Design Of Clpp Activators As Novel Antibiotics, Schyler Odum

Theses and Dissertations (ETD)

Purpose. Design and synthesize novel compounds to treat Staphylococcus aureus infections by targeting the dysregulation of the Casein Protease P, ClpP. Methods. Utilize established chemical methods to synthesize ureadepsipeptides, small-molecule ClpP activators, and ureadepsipeptide hybrids. Assess their effectiveness by using minimum inhibitory concentration assays and in vitro biochemical assays for ClpP activation. Explore their potential as antibiotics through mitochondrial toxicity tests, glucose/galactose assays, and biophysical measurements related to metabolism and clearance, including thermal shift and surface plasmon resonance assays. Results. Synthesized and tested 33 novel compounds, comprising a total of 80 synthetic steps. Conclusion. The three-part conclusion from the dissertation …

Reelin Regulation Of Striatal Physiology And Cocaine Reward, Kasey Lynn Brida

All ETDs from UAB

Drugs of abuse activate defined neuronal populations in brain reward structures such as the nucleus accumbens (NAc), which are thought to promote the enduring synaptic, circuit, and behavioral consequences of drug exposure. While the molecular and cellular effects arising from experience with drugs like cocaine are increasingly well understood, the mechanisms that sculpt NAc neuron participation are largely unknown. Here, we leveraged unbiased single-nucleus transcriptional profiling to identify expression of the secreted glycoprotein Reelin (encoded by the Reln gene) as a marker of cocaine-activated neurons within the rat NAc. Multiplexed in situ detection confirmed selective expression of the immediate early …

Investigating Potential Therapeutic Vulnerabilities And Elucidating Molecular Mechanisms For The Tumor Suppressors Nfkbia And Anxa7 In Diffuse Gliomas, Aran Merati

All ETDs from UAB

Gliomas, and especially diffuse gliomas, can be a devastating disease when attempting treatment in the clinic. Diffuse gliomas are typically malignant and pose definitive problems with respect to patient care predominantly due to their ability to exist outside of the bulk tumor by invading into the surrounding brain parenchyma. Consequently, not every cancerous cell can be fully removed by surgical resection and therapeutic resistance, so the stem-like population left behind can repopulate a recurrent tumor from a single cell. There is a desperate need for pinpointing novel therapeutic vulnerabilities in diffuse gliomas, which could potentially involve the targeting of key …

Maternal Immune Activation Causes Oligodendrocyte Deficits In The Hypothalamus, Kate Miller

All ETDs from UAB

Maternal immune activation (MIA) refers to the occurrence of an inflammatory immune response during any stage of pregnancy. This manifests as the upregulation of proinflammatory cytokines and can be caused by air pollution, obesity, or viral infection. When this occurs during the first trimester in humans, it increases the offspring’s susceptibility to developing neuropsychiatric disorders such as autism (ASD) and schizophrenia (SZ), in males more commonly than females. In addition to behavioral manifestations of neuropsychiatric disorders, metabolic syndrome (MetS) is a common comorbidity, defined as the co-occurrence of three or more symptoms including but not limited to hyperlipidemia, hypertension, and …

Weighted Family History Density Of Substance Use: Influence On Participant Substance Use Onset, Escalation, And Duration, Carleigh A. Litteral

Theses and Dissertations--Psychology

Substance use disorders impose a staggering toll on the United States (U.S.), straining healthcare systems, destabilizing communities, and profoundly impacting both individuals and families. Approximately one in six Americans aged 12 and older had a past-year substance use disorder in 2022 (Key Substance Use, 2022), and nearly one-third of adults experience a substance use disorder in their lifetime (Wu, 2010), contributing to an economic burden exceeding $400 billion annually (National Drug Threat Assessment, 2011). Family history of substance use disorders is a key predictor of vulnerability, with individuals who have affected relatives being 2–8 times more …

The Bacterial Sensing Nuclear-Oligomerization Domain 2 Receptor In The Brain: Location And Potential Function, Julia Smyth

Dissertations

Nucleotide-binding oligomerization domain-2 (NOD2) is a cytosolic receptor, activated by bacterial peptides that initiates innate immune responses through nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and Caspase-1 pathways. While the role of NOD2 in inflammation outside the central nervous system (CNS) is well-established, especially in the gastrointestinal system, its expression and function in the brain remain poorly defined. Previous genetic studies suggest a link between NOD2 and neurological and psychiatric conditions, including stroke, Parkinson’s disease, and schizophrenia. However, information regarding NOD2 expression, localization, and function in the CNS is limited. In this work, we investigated NOD2 expression, localization, and regulation …

Deep Dive In Sound Filtering, Cecilia Zoutewelle

A. The Science of Sound

A 7-page report, with illustrations and bullet-point summaries, on the ways we filter sounds as part of the standard process of hearing. Includes brief considerations of evolution, selective listening in conversations, and listening bias.

Neuropsychological Assessment Accuracy In Diagnosing Early-Onset Alzheimer’S Disease, Elise Thomas

Master's Theses and Doctoral Dissertations

Early-onset Alzheimer’s disease (EOAD), a progressive neurological condition, is often difficult to diagnose before substantial neuronal damage. Neuropsychological assessments offer a more cost-effective and accessible method for detecting early cognitive decline, yet limited research exists on optimal combinations for EOAD identification. This study analyzed data from 24 clinical studies to determine the diagnostic accuracy of FDA-approved EOAD assessments used in combination. No single combination was found to be superior across all diagnostic metrics. MMSE + MoCA + ADAS-Cog showed the highest sensitivity, MMSE + MoCA + RBANS the highest specificity, MMSE + RBANS the highest AUC value, and MMSE + …

Re-Stenting Following Recurrence After Successful Venous Sinus Stenosis Stenting For Idiopathic Intracranial Hypertension, Salvatore A D'Amato, Juan Carlos Martinez Gutierrez, Hussein A Zeineddine, Eric Claude Mohan, Tien Nguyen, Cybele Woon, Rosa Tang, Peng Roc Chen

Faculty, Staff and Student Publications

Objective: In medically refractory idiopathic intracranial hypertension (IIH), venous sinus stenosis (VSS) stenting has been an effective treatment modality. Among patients who experience recurrent symptoms and develop new stenosis, the optimal treatment strategy is unknown. The aim of this study was to investigate the role of rescue re-stenting in patients with recurrence after prior successful stenting.

Methods: This was a single center, retrospective review from a prospectively maintained IIH registry. Between 2012 and 2023, patients who underwent interventions for confirmed IIH and angiographically demonstrable VSS were included. The cohort was divided into those who underwent a single stenting procedure (single …

Association Of High-Sensitivity Cardiac Troponin I Levels Below The Sex-Specific 99th Percentile With Late-Life Dementia: The Perth Longitudinal Study Of Ageing Women, Carlos J. Toro-Huamanchumo, Abadi Kahsu Gebre, Tiago Pecanha, Craig Sale, Wai Lim, Elizabeth Byrnes, Ee Mun Lim, Simon Laws, Kun Zhu, Carl Schultz, Richard L. Prince, Blossom C.M. Stephan, Mario Siervo, Joshua R. Lewis, Marc Sim

Research outputs 2022 to 2026

Background: Elevated high-sensitivity cardiac troponin (hs-cTn) levels are linked with cardiovascular disease and cognitive impairment, both of which are strong risk factors for late-life dementia (LLD). This study examined the association between hs-cTnI levels below the sex-specific 99th percentile for myocardial injury and the incidence of LLD in older women. Methods: 986 community-dwelling women aged ≥70 years without prior LLD and with hs-cTnI < 15.6 ng/L (stratified into quartiles) were included from the Perth Longitudinal Study of Ageing Women. The primary outcome was incident LLD events, including LLD hospitalisation or death, over 14.5 years obtained from linked health records. Associations between hs-cTnI and LLD outcomes were explored using multivariable-adjusted Cox models, as part of restricted cubic splines. Results: At baseline, participants' mean (±SD) age was 75.2±2.7 years. Over 14.5 years of follow-up, LLD events (n=174, 17.7%), hospitalisations (n=155, 15.7%) and deaths (n=68, 6.9%) were recorded. Compared with those in the lowest quartile (Q1, median 3.1 ng/L), women in the highest quartile of hs-cTnI (Q4, median 7.3 ng/L) had a greater risk of developing LLD-related events (adjusted HR: 1.88, 95% CI: 1.22 to 2.91), hospitalisation (adjusted HR: 1.65, 95% CI: 1.04 to 2.64) and death (adjusted HR: 2.27, 95% CI: 1.13 to 4.59), after adjusting for established cardiovascular and dementia risk factors, including apolipoprotein E (APOE) genotype. Conclusion: Among older women, hs-cTnI levels below the sex-specific 99th percentile for myocardial injury were associated with an increased risk of LLD events over 14.5 years. These findings suggest that hs-cTnI may identify older women at higher risk of LLD, capturing both cardiovascular and brain health vulnerability in older age.

Exploring Non-Invasive Brain Stimulation Effects On Physical Outcomes In People With Parkinson’S Disease: An Umbrella Evidence Mapping Review With Meta-Analyses, Dale M. Harris, Christopher Latella, Nicholas Tripodi, Steven J. O’Bryan

Research outputs 2022 to 2026

Background: Non-invasive brain stimulation (NIBS) is sometimes used alongside medication to alleviate motor symptoms in people with Parkinson’s disease (PD). However, the evidence supporting NIBS’s effectiveness for improving motor function in PD patients is uncertain.

Objective: This umbrella review aims to synthesize recent systematic reviews and meta-analyses that have evaluated the effectiveness of NIBS in improving motor function in people with PD, with a key focus being to examine the quality of the evidence presented. Methods: The review protocol was registered in PROSPERO (CRD42022380544) and conducted per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search strategy was …

Effects Of Perinatal Exposure To Lipopolysaccharide And Acetaminophen On Learning In Adult Long-Evans Rats, Lucy A. Sivils

College of Graduate Studies: Theses & Dissertations

The present study investigated the individual and combined effects of elevated perinatal inflammation, oxidative stress caused by acetaminophen (APAP) exposure, or elevated inflammation and oxidative stress on adult learning behaviors in Long-Evans rats. While prior studies have examined these factors independently, the combined effects of inflammation and oxidative stress via APAP exposure during early development on learning-related behaviors remain unexplored. The present research aimed to address this gap by the analysis of potential long-term neurodevelopmental consequences of lipopolysaccharide (LPS)-induced inflammation and APAP-induced oxidative stress. LPS, APAP, or LPS + APAP was administered during the perinatal period: postnatal days (PD) 9, …

Impact Of Tranexamic Acid On Patient Outcomes In Intracranial Hemorrhage: A Review, William G. Johnson

The PA Department Journal of Medical Science

Introduction: Intracranial hemorrhage is a medical emergency that remains a significant source of death and disability for patients globally. Tranexamic acid has shown promise in treating trauma related bleeding loss in various settings. This study aims to evaluate its role in the management of intracranial hemorrhages.

Methods: A review of data in the PubMed National Library of Medicine was conducted to find relevant and reputable studies related to this topic. Using the search “tranexamic acid AND intracranial hemorrhage*” and the following filters: last 5 years, free full text, English language, including RCTs, meta-analyses, and systematic reviews, 13 results …

Resort Enhances Reference-Based Cell Type Deconvolution For Spatial Transcriptomics Through Regional Information Integration, Linhua Wang, Ling Wu, Guantong Qi, Chaozhong Liu, Wanli Wang, Xiang H-F Zhang, Zhandong Liu

Duncan NRI Faculty and Staff Publications

Motivation: Spatial transcriptomics (ST) captures positional gene expression within tissues but lacks single-cell resolution. Reference-based cell type deconvolution methods were developed to understand cell type distributions for ST. However, batch/platform discrepancies between references and ST impact their accuracy.

Results: We present Region-based Cell Sorting (ReSort), which utilizes ST's region-level data to lessen reliance on reference data and alleviate these technical issues. In simulation studies, ReSort enhances reference-based deconvolution methods. Applying ReSort to a mouse breast cancer model highlights macrophages M0 and M2 enrichment in the epithelial clone, revealing insights into epithelial-mesenchymal transition and immune infiltration.

Availability and implementation: Source codes …

Survey And Improvement Strategies For Gene Prioritization With Large Language Models, Matthew B Neeley, Guantong Qi, Guanchu Wang, Ruixiang Tang, Dongxue Mao, Chaozhong Liu, Sasidhar Pasupuleti, Bo Yuan, Fan Xia, Pengfei Liu, Zhandong Liu, Xia Hu

Duncan NRI Faculty and Staff Publications

Motivation: Rare diseases remain difficult to diagnose due to limited patient data and genetic diversity, with many cases remaining undiagnosed despite advances in variant prioritization tools. While large language models have shown promise in medical applications, their optimal application for trustworthy and accurate gene prioritization downstream of modern prioritization tools has not been systematically evaluated.

Results: We benchmarked various language models for gene prioritization using multi-agent and Human Phenotype Ontology classification approaches to categorize patient cases by phenotype-based solvability levels. To address language model limitations in ranking large gene sets, we implemented a divide-and-conquer strategy with mini-batching and token limiting …

Drosophila Models Uncover Substrate Channeling Effects On Phospholipids And Sphingolipids In Peroxisomal Biogenesis Disorders, Michael F Wangler, Yu-Hsin Chao, Mary Roth, Ruth Welti, James A Mcnew

Duncan NRI Faculty and Staff Publications

Peroxisomal Biogenesis Disorders Zellweger Spectrum (PBD-ZSD) disorders are a group of autosomal recessive defects in peroxisome formation that produce a multi-systemic disease presenting at birth or in childhood. Well documented clinical biomarkers such as elevated very long chain fatty acids (VLCFA) are key biochemical diagnostic findings in these conditions. Additional, secondary biochemical alterations such as elevated very long chain lysophosphatidylcholines are allowing newborn screening for peroxisomal disease. In addition, a more widespread impact on metabolism and lipids is increasingly being documented by metabolomic and lipidomic studies. Here we utilize Drosophila models of pex2 and pex16 as well as human plasma …

Recurrent Carotid Paragangliomas In A Syndromic Patient With A Heterozygous Missense Variant In Dna Methyltransferase 3 Alpha, Ryan J German, Blake Vuocolo, Liesbeth Vossaert, Lisa Saba, Robin Fletcher, Matthew L Tedder, Bekim Sadikovic, Jennifer Kerkhof, Michael Wangler, Carlos A Bacino

Duncan NRI Faculty and Staff Publications

We report a 40-year-old African American female with a novel variant in exon 8 of DNA methyltransferase 3 alpha (DNMT3A), (NM_022552.4: c.905G>C, p.G302A) who presented with a history of recurrent carotid paragangliomas, mediastinal mass, intellectual disability, dysarthria, cholelithiasis, diabetes mellitus, hypertension, and dysmorphic features. We interpret this novel variant as likely pathogenic and causative for the patient's syndromic features of Heyn-Sproul-Jackson syndrome. Heyn-Sproul-Jackson syndrome is a condition caused by gain-of-function genetic changes in DNMT3A. Paragangliomas have also been observed in non-syndromic patients with genetic alterations in DNMT3A. We describe a patient with clinical features of Heyn-Sproul-Jackson syndrome such as …