Medical Sciences Commons^™

Development Of A Chemical Biology Approach To Uncover The Influence Of Sequence Variations On Ces1 Activity In Live Cells, Samuel James Knebel

Masters Theses

Drug metabolism is the biochemical process of modifying drugs to detoxify and remove them through enzymatic transformations. These biotransformation’s occur primarily in the liver and are critical to understanding how pharmaceutical compounds are chemically altered inside the human body. Human carboxylesterases (CESs) catalyze the hydrolysis of esters, amides, thioesters, and carbamates. CES-mediated hydrolysis plays an important role in the metabolism of many drugs including the first FDA approved antiviral treatment for COVID-19, remdesivir (Veklury), the seizure control medication rufinamide (Banzel), and the flu antiviral drug oseltamivir (Tamiflu). CES activity is known to be influenced by a variety of factors including …

Dermatological Concerns For Women And Girls With Turner Syndrome, David Rodriguez-Buritica, Meaghan Mones, Siddharth K Prakash, Michelle Rivera, Melissa Aldrich, Megan Rogge, Kate Richardson

Faculty, Staff and Student Publications

Introduction: Turner syndrome (TS) is associated with distinct manifestations in women and girls including short stature, cardiac abnormalities, premature ovarian failure as well as dermatological features, including lymphedema, keloids, onychodystrophy, and acne. Although many dermatological concerns present during the first few decades of life, the overwhelming majority of respondents are not provided with dermatology referrals at diagnosis.

Methods: This cross-sectional study utilized an author designed survey to assess self-reported dermatological manifestations, dermatology referral experience, common therapies for select dermatological conditions, as well as a validated 10-question Dermatology Life Quality Index (DLQI) to assess quality-of-life impact in women and girls with …

Investigating The Electrostatics Of Mucins As Key Contributors To Mucus Stasis In Cystic Fibrosis, Elex Skylar Rose

All ETDs from UAB

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a channel responsible for the transport of chloride and bicarbonate ions across the apical cell surface. In the respiratory tract, defective CFTR results in viscous and adherent mucus that becomes static within the airway, which leads to chronic infections, progressive lung damage, and early mortality. Historically, CF mucus stasis has been attributed to significant airway dehydration; however, growing evidence has demonstrated that aberrant electrostatic properties of mucins also contribute to mucus stasis in CF. Mucins are large, polymeric glycoproteins …

Developmental Patterning Of Peptide Transcription In The Central Circadian Clock In Both Sexes, Vania Carmona-Alcocer, Lindsey S. Brown, Aisha Anchan, Kayla E. Rohr, Jennifer A. Evans

Biomedical Sciences Faculty Research and Publications

Introduction: Neuropeptide signaling modulates the function of central clock neurons in the suprachiasmatic nucleus (SCN) during development and adulthood. Arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP) are expressed early in SCN development, but the precise timing of transcriptional onset has been difficult to establish due to age-related changes in the rhythmic expression of each peptide.

Methods: To provide insight into spatial patterning of peptide transcription during SCN development, we used a transgenic approach to define the onset of Avp and Vip transcription. Avp-Cre or Vip-Cre males were crossed to Ai9^+/+ females, producing offspring in which the fluorescent protein …

On The Origin And Evolution Of The Dual Oscillator Model Underlying The Photoperiodic Clockwork In The Suprachiasmatic Nucleus, Jennifer A. Evans, William J. Schwartz

Biomedical Sciences Faculty Research and Publications

Decades have now passed since Colin Pittendrigh first proposed a model of a circadian clock composed of two coupled oscillators, individually responsive to the rising and setting sun, as a flexible solution to the challenge of behavioral and physiological adaptation to the changing seasons. The elegance and predictive power of this postulation has stimulated laboratories around the world in searches to identify and localize such hypothesized evening and morning oscillators, or sets of oscillators, in insects, rodents, and humans, with experimental designs and approaches keeping pace over the years with technological advances in biology and neuroscience. Here, we recount the …

Attitudes Toward Implicit Bias Among Ncaa Medical Support Staff, B J. Warner, A P. Jacobsen, M Decker, S A. Cage

Clinical Practice in Athletic Training

Introduction: Implicit biases are unconscious attitudes, emotions, or stereotypes that have the potential to negatively affect behaviors, actions, and decisions. Recent research has shown that healthcare workers do not provide equitable care to patients from different demographics. When patients are receiving different levels of care, there is a potential for different patient-related outcomes. One of their first steps in many implicit bias interventions for healthcare professionals is identifying one’s implicit bias. The purpose of this study was to describe the attitudes toward implicit bias among non-athletic training healthcare professionals who provide care to collegiate student-athletes. Methods: An electronic survey was …

Low Ferritin Count In Female Collegiate Soccer Player Presents As Concussion, E N. Nelson, T D. Pitcock, M K. Knoblauch, L J. Harrison

Clinical Practice in Athletic Training

Background: Women’s soccer leads the National Collegiate Athletic Association for having the highest number of concussions in female sports. Common symptoms of concussion can include light headedness, headaches, and dizziness, but these symptoms are not exclusive to concussions. Female athletes may experience nutritional deficits that can lead to a wide range of symptoms mimicking those commonly experienced with a concussion such as headaches, dizziness, and fatigue. The patient in this case is a 21- year-old female soccer athlete who presented with sensitivity to light, light headedness, nausea, and fatigue after experiencing repeated ‘headers’ as well as a collision during a …

Figure-8-Reconstruction Of Posterior Sternoclavicular Joint Dislocation 18 Days Post Initial Injury, M Suri, S Bunemann

Clinical Practice in Athletic Training

Introduction: Traumatic sternoclavicular joint injuries account for less than 3% of all traumatic joint injuries1. Although rare, posterior dislocation of the sternoclavicular joint has the potential to be life-threatening due to the proximity of vital structures posterior to the manubrium. This injury typically requires a high-energy force applied through the joint2. SC dislocations become increasingly difficult to reduce after 24 hours, so timely diagnosis and treatment are important. Glass et al. found mediastinal compression occurred 30% of the time with posterior dislocations. If left untreated, prolonged pressure on the superior mediastinum can cause erosion of the great vessels, tracheoesophageal fistula, …

Smart Offloading Boot System For Remote Patient Monitoring: Toward Adherence Reinforcement And Proper Physical Activity Prescription For Diabetic Foot Ulcer Patients, Catherine Park, Ramkinker Mishra, Davide Vigano, Maurizio Macagno, Stefano Rossotti, Karen D'Huyvetter, Jason Garcia, David G Armstrong, Bijan Najafi

Center on Aging Staff Publications

Background: A critical factor in healing diabetic foot ulcers is patient adherence to offloading devices. We tested a smart offloading boot (SmartBoot) combined with a smartwatch app and cloud dashboard to remotely monitor patient adherence and activity. In addition, the impact of SmartBoot on balance, gait, and user experience was investigated.

Methods: Fourteen volunteers (31.6±8.7 years; 64% female) performed natural activities (eg, sitting, standing, walking) with and without the SmartBoot for approximately 30 minutes. All participants completed balance tests, 10-meter walking tests at slow, normal, and fast pace while wearing the SmartBoot, and a user experience questionnaire. The accuracy of …

Home-Based Electrical Stimulation To Accelerate Wound Healing-A Double-Blinded Randomized Control Trial, Alejandro Zulbaran-Rojas, Catherine Park, Nesreen El-Refaei, Brian Lepow, Bijan Najafi

Center on Aging Staff Publications

Background: Electrical stimulation (E-Stim) may offer a unique adjunctive treatment to heal complicated diabetic foot ulcers (DFU). Our primary goal is to examine the effectiveness of daily home-based E-Stim therapy to speed-up wound healing.

Methods: Patients with chronic DFUs and mild to severe peripheral arterial disease (PAD) were recruited and randomized to either control (CG) or intervention (IG) groups. The IG received 1-hour home-based E-Stim therapy on daily basis for 4 weeks (4W). E-Stim was delivered through electrical pads placed above the ankle joint using a bio-electric stimulation technology (BEST®) platform (Tennant Biomodulator® PRO). The CG was provided with an …

Social Behavioral Impairments In Syngap1-Related Intellectual Disability, Hajer Naveed, Maria Mccormack, J Lloyd Holder

Duncan NRI Faculty and Staff Publications

Introduction: Developmental synaptopathies are neurodevelopmental disorders caused by genetic mutations disrupting the development and function of neuronal synapses.

Methods: We administered the validated Social Responsiveness Scale, Second Edition (SRS-2) to investigate the phenotypic presentation of social-behavioral impairments for the developmental synaptopathy-SYNGAP1-related Intellectual Disability (SYNGAP1-ID) (n = 32) compared with a phenotypically similar disorder Phelan-McDermid syndrome (PMD) (n = 27) and healthy controls (n = 43). A short form SRS-2 analysis (n = 85) was also conducted.

Results: Both SYNGAP1-ID and PMD had significantly elevated total and subcategory T-scores, with no significant score differences between SYNGAP1 …

Upregulation Of The Escrt Pathway And Multivesicular Bodies Accelerates Degradation Of Proteins Associated With Neurodegeneration, Ron Benyair, Sai Srinivas Panapakkam Giridharan, Pilar Rivero-Ríos, Junya Hasegawa, Emily Bristow, Eeva-Liisa Eskelinen, Merav D Shmueli, Vered Fishbain-Yoskovitz, Yifat Merbl, Lisa M Sharkey, Henry L Paulson, Phyllis I Hanson, Samarjit Patnaik, Ismael Al-Ramahi, Juan Botas, Juan Marugan, Lois S Weisman

Duncan NRI Faculty and Staff Publications

Many neurodegenerative diseases, including Huntington’s disease (HD) and Alzheimer’s disease (AD), occur due to an accumulation of aggregation-prone proteins, which results in neuronal death. Studies in animal and cell models show that reducing the levels of these proteins mitigates disease phenotypes. We previously reported a small molecule, NCT-504, which reduces cellular levels of mutant huntingtin (mHTT) in patient fibroblasts as well as mouse striatal and cortical neurons from an HdhQ111 mutant mouse. Here, we show that NCT-504 has a broader potential, and in addition reduces levels of Tau, a protein associated with Alzheimer’s disease, as well as other tauopathies. We …

Hpv-Related Oropharyngeal Cancer Early Detection In Gay And Bisexual Men Is An “Orphan” Practice: A Qualitative Analysis Among Healthcare Providers, I Niles Zoschke, Sarah L Bennis, J Michael Wilkerson, Cynthia L Stull, Alan G Nyitray, Samir S Khariwala, C Mark Nichols, B R Simon Rosser, Charlene Flash, Michael W Ross

Faculty, Staff and Student Publications

Introduction: Among US men, oropharyngeal cancer (cancer of the back of the mouth and throat) is the 8th most common cancer. If detected early, human papillomavirus (HPV)-16-associated oropharyngeal cancer has a high 5-year survival rate. Risk factors such as high numbers of oral sex partners, disparities in smoking and drinking, and low rates of HPV vaccination may put gay and bisexual men at even higher risk for oropharyngeal cancer.

Methods: We recruited 21 healthcare providers in Minneapolis-St. Paul, Minnesota and Houston, Texas to participate in semi-structured interviews. Nurses, physician assistants, dental hygienists, and dentists were asked about their clinical experiences …

Identification Of Microbiological Factors Associated With Periodontal Health Disparities, Bing-Yan Wang, Aize Cao, Meng-Hsuan Ho, Derek Wilus, Sally Sheng, Hsiu-Wan Meng, Elissa Guerra, Jianming Hong, Hua Xie

Faculty, Staff and Student Publications

The present study aimed at identifying risk factors associated with periodontitis development and periodontal health disparities with emphasis on differential oral microbiota. The prevalence of periodontitis is recently rising dentate adults in the US, which presents a challenge to oral health and overall health. The risk of developing periodontitis is higher in African Americans (AAs), and Hispanic Americans (HAs) than in Caucasian Americans (CAs). To identify potentially microbiological determinations of periodontal health disparities, we examined the distribution of several potentially beneficial and pathogenic bacteria in the oral cavities of AA, CA, and HA study participants. Dental plaque samples from 340 …

Sphingolipids In Neurodegenerative Diseases, Xueyang Pan, Debdeep Dutta, Shenzhao Lu, Hugo J Bellen

Faculty, Staff and Students Publications

Neurodegenerative Diseases (NDDs) are a group of disorders that cause progressive deficits of neuronal function. Recent evidence argues that sphingolipid metabolism is affected in a surprisingly broad set of NDDs. These include some lysosomal storage diseases (LSDs), hereditary sensory and autonomous neuropathy (HSAN), hereditary spastic paraplegia (HSP), infantile neuroaxonal dystrophy (INAD), Friedreich’s ataxia (FRDA), as well as some forms of amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD). Many of these diseases have been modeled in Drosophila melanogaster and are associated with elevated levels of ceramides. Similar changes have also been reported in vertebrate cells and mouse models. Here, we …

Mass Spectrometry Imaging As An Emerging Tool For Studying Metabolism In Human Brain Organoids, Gerarda Cappuccio, Saleh M Khalil, Sivan Osenberg, Feng Li, Mirjana Maletic-Savatic

Faculty, Staff and Students Publications

Human brain organoids are emerging models to study human brain development and pathology as they recapitulate the development and characteristics of major neural cell types, and enable manipulation through an in vitro system. Over the past decade, with the advent of spatial technologies, mass spectrometry imaging (MSI) has become a prominent tool for metabolic microscopy, providing label-free, non-targeted molecular and spatial distribution information of the metabolites within tissue, including lipids. This technology has never been used for studies of brain organoids and here, we set out to develop a standardized protocol for preparation and mass spectrometry imaging of human brain …

Cerebellar Dysfunction In Rodent Models With Dystonia, Tremor, And Ataxia, Meike E Van Der Heijden, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Dystonia is a movement disorder characterized by involuntary co- or over-contractions of the muscles, which results in abnormal postures and movements. These symptoms arise from the pathophysiology of a brain-wide dystonia network. There is mounting evidence suggesting that the cerebellum is a central node in this network. For example, manipulations that target the cerebellum cause dystonic symptoms in mice, and cerebellar neuromodulation reduces these symptoms. Although numerous findings provide insight into dystonia pathophysiology, they also raise further questions. Namely, how does cerebellar pathophysiology cause the diverse motor abnormalities in dystonia, tremor, and ataxia? Here, we describe recent work in rodents …

Function And Dysfunction Of The Dystonia Network: An Exploration Of Neural Circuits That Underlie The Acquired And Isolated Dystonias, Jason S Gill, Megan X Nguyen, Mariam Hull, Meike E Van Der Heijden, Ken Nguyen, Sruthi P Thomas, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Dystonia is a highly prevalent movement disorder that can manifest at any time across the lifespan. An increasing number of investigations have tied this disorder to dysfunction of a broad "dystonia network" encompassing the cerebellum, thalamus, basal ganglia, and cortex. However, pinpointing how dysfunction of the various anatomic components of the network produces the wide variety of dystonia presentations across etiologies remains a difficult problem. In this review, a discussion of functional network findings in non-mendelian etiologies of dystonia is undertaken. Initially acquired etiologies of dystonia and how lesion location leads to alterations in network function are explored, first through …

An Initial Experience Of Completion Hemispherotomy Via Magnetic Resonance-Guided Laser Interstitial Therapy, Vijay M Ravindra, Lucia Ruggieri, Nisha Gadgil, Angela P Addison, Ilana Patino, David D Gonda, Jason Chu, Laura Whitehead, Anne Anderson, Gloria Diaz-Medina, Kimberly Houck, Akshat Katyayan, Laura Masters, Audrey Nath, Michael Quach, James John Riviello, Elaine Seto, Krystal Elizabeth Sully, Latanya Agurs, Sonali Sen, Maureen Handoko, Rohini Coorg, Irfan Ali, Daniel Ikeda, Howard Weiner, Daniel J Curry

Duncan NRI Faculty and Staff Publications

Introduction: In carefully selected patients with medically refractory epilepsy, disconnective hemispherotomy can result in significant seizure freedom; however, incomplete disconnection can result in ongoing seizures and poses a significant challenge. Completion hemispherotomy provides an opportunity to finish the disconnection. We describe the use of magnetic resonance-guided laser interstitial thermal ablation (MRgLITT) for completion hemispherotomy.

Methods: Patients treated with completion hemispherotomy using MRgLITT at our institution were identified. Procedural and seizure outcomes were evaluated retrospectively.

Results: Five patients (3 males) underwent six MRgLITT procedures (one child treated twice) for completion hemispherotomy at a median age of 6 years (range 1.8-12.9). Two …

Investigating The Viral Nature Of Neuronal Capsid Genes, Michael Manuel Long

Master's Theses

Memory formation is an essential part of everyday life. Neuronal communication is thought to be a key driver behind memory formation. There are two heavily studied methods of neuronal communication: chemical (neurotransmitter-mediated) and electrical (physically attached). When issues arise environmentally or genetically, people can experience one of many devastating memory disorders i.e. Alzheimer’s disease and other Dementias. Due to their prevalence, the treatments for disorders that hinder memory formation are a high priority for pharmaceutical companies. Currently, many of the treatments available focus on neurotransmitters or neuronal activity, and scientists are far from a cure. However, there may be an …

A Descriptive And Visual Analysis Of The North Coast Fall Prevention Survey Data, Mishell Lopez

Cal Poly Humboldt theses and projects

Older adults over 65 will double from 52.4 million in 2018 to 94.7 million in 2060. Among this aging group, falls affect one out of four older adults and are a critical economic concern for our American society, with yearly costs of $50 billion. In older adults, falling can result in negative consequences such as fear of falling, injuries, mobility restrictions, and loss of independence. California has one of the highest costs per fall ($4 billion annually) and a high percentage of adults who have fallen (30.6%) compared to the nation. Moreover, two of California’s northwest rural counties, Del Norte, …

Factors Associated With Patient Portal Utilization, Preventive Services Utilization, And Health Promoting Behaviors Among Adults In The United States, Elizabeth Ayangunna

College of Graduate Studies: Theses & Dissertations

Background: Nearly 60% of adults in the United States are estimated to have one or more chronic conditions, necessitating strategies to improve the health status of persons with chronic disease. Given that health information technology (HIT) is considered highly valuable for superior disease management, it is imperative to examine how HIT use can improve health behaviors, which can in turn improve health status. This study aimed to examine if there was an association between patient portal utilization and the use of preventive services & health-promoting behaviors. Also, this study examined the influence of self-efficacy on preventive health behaviors among adults …

Il-27 Negatively Impacts Immunity Developed Following Bcg Administration, Shelby D. Bradford

Graduate Theses, Dissertations, and Problem Reports (ETD)

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), a predominantly respiratory pathogen responsible for over ten million infections and one million deaths last year. Despite it being a primary objective of the World Health Organization (WHO) for several decades to irradicate TB, progress toward this objective has fallen short of the 2020 target to end TB by 2035. Meeting this goal will require advancements in diagnostic tools, education, healthcare access, and treatments and preventatives. Regarding prevention, the primary tool for this strategy is through vaccination. Currently, the only licensed vaccine for protection against TB is the century old …

Longitudinal Oxygen Imaging In 3d (Bio)Printed Models, Ryan Curtis O'Connell

Graduate Theses, Dissertations, and Problem Reports (ETD)

Electron paramagnetic resonance (EPR), and its molecular imaging modality, is a powerful tool to noninvasively map various biological and chemical markers within objects of interest. Reliable data acquisition is a major impeding factor for longitudinal hands-off measurements. Measurements are especially challenging in biomedical applications, as live objects are not static. Frequent changes occur that require constant fine recalibration of the EPR detection system, called the resonator. To enable longitudinal imaging, a technology permitting automatic digital control of resonator coupling, tuning, and EPR data acquisition was developed. Automation was achieved through the utilization of a microcontroller and digital peripheral components such …

Regulating Cancer Cell Metabolism During Hypoxia-Reoxygenation: Examing The Interplay Of Gasotransmitters And Glutaminolysis, Dianna L. Xing

All ETDs from UAB

Oxidative phosphorylation is an oxygen-dependent metabolic process that provides the majority of ATP used to support essential cellular functions. However, in cancer, limitations in oxygen availability occur during the development and metastasis of tumors. To compensate for the demands of rapidly proliferating cells, many cancers exhibit an increased demand for glycolysis, the TCA cycle, and glutaminolysis. In this thesis, extracellular flux technology and metabolomics were applied in a hypoxia-reoxygenation model to investigate the metabolic adaptations that occur in dynamic changes in oxygen and nutrient availability in cancer cells. We show the significance of glutaminolysis and its substrates in regulating cancer …

Transcriptional Regulation In Early Stage Cd4+ T Cell Activation And Differentiation, Andrew Ray Schroeder

All ETDs from UAB

CD4+ T cells regulate the humoral and cellular immune responses by differentiating into T follicular helper (Tfh) cells or into non-Tfh effector cells. Non-Tfh effector cells leave the lymph node and migrate to the effector site whereas Tfh cells upregulate CXCR5 and migrate towards the B cell follicle. The mechanism of CXCR5 induction, however, is still incompletely understood. The transcription factor Bach2 was shown to inhibit the in vitro differentiation of Th1, Th2, and Th17 cells as well as the in vivo Tfh responses. Though, it is unknown how Bach2 arbitrates Tfh and non-Tfh differentiation in vivo. Here, we report …

The Effects Of Cannabidiol On Brain Temperature In Treatment-Resistant Epilepsy, Ayushe A. Sharma

All ETDs from UAB

Epilepsy affects over 70 million people worldwide with a global incidence of 2.4 million new cases per year. In many of these patients, neuroinflammation (NI) is a key pathological contributor to focal seizure generation and maintenance. Sustained NI degrades the blood–brain barrier, leads to neuronal death, and ultimately decreases seizure threshold. Finding ways to image and treat NI is especially important for the >30% of patients with treatment-resistant epilepsy (TRE) who cannot achieve seizure freedom with standard antiseizure medications. Cannabidiol (CBD) effectively reduces seizure frequency and severity in many TRE patients, although its antiepileptic effects remain poorly understood. Atypically high …

Interactions Between Pseudomonas Aeruginosa And The Oral Commensal Streptococcus Salivarius, Sara Noelle Stoner

All ETDs from UAB

The cystic fibrosis airway is a polymicrobial environment often dominated by opportunistic pathogens such as Pseudomonas aeruginosa, a leading cause of lung function decline and mortality in persons with CF. Commensal streptococcal colonization has been associated with stable CF lung function in multiple studies. However, few studies have examined interactions between P. aeruginosa and commensals as well as their impact on P. aeruginosa airway infections. In the first half of this work, we studied interactions between P. aeruginosa and the oral commensal Streptococcus salivarius within a biofilm setting. We found that S. salivarius biofilm formation is promoted by the non-mucoid …

Investigating The P53 Tumor-Suppressive Network And The Dynamics/Mechanism Of P53 Loss Of Heterozygosity, Jun Wang

All ETDs from UAB

Tumor suppressor gene TP53 is the most frequently mutated gene across human cancers (~50%). Patients with Li-Fraumeni syndrome (LFS) who carry germline p53 mutations exhibit a diverse spectrum of childhood- and adult-onset malignancies. Despite over 40 years of dedicated studies to understand the role of p53 in tumor prevention, there are still many unanswered questions regarding the underlying mechanisms of p53. Previous studies have supported the notion that p53 exerts its tumor-suppressive function through its transcriptional activities. Therefore, strategies to enhance p53’s functions in tumor suppression via manipulating of downstream target gene activities in cancers show promising. To better investigate …

Cis-Regulatory Elements: Relevance For Alzheimer's Disease, Brianne Brazell Rogers

All ETDs from UAB

Alzheimer’s disease (AD) is the most common neurodegenerative disease, currently affecting more than six million Americans with limited treatment options. Identifying genetics contributors to neurodegenerative diseases has contributed critical insights into potential disease mechanisms. The majority of disease-associated genetic variants are located in non-coding regions, likely in regulatory elements, and affect the expression of target genes whose function contributes to neurodegeneration. Here, I performed a case-control study utilizing nuclei from dorsolateral prefrontal cortex postmortem tissue to correlate chromatin accessibility with gene expression and nominate 40,831 AD-specific candidate cis-regulatory elements. Additionally, work in this dissertation nominates ZEB1 and MAFB as candidate …