Digital Commons Network^™

Aconitate Decarboxylase 1 Mediates The Acute Airway Inflammatory Response To Environmental Exposures, Aaron Schwab, Amy J. Nelson, Angela Gleason, Oliver Schanze, Todd A. Wyatt, Dhananjay Shinde, Peng Xiao, Vinai Chittezham Thomas, Chittibabu Guda, Kristina L. Bailey, Tammy Kielian, Geoffrey M. Thiele, Jill A. Poole

Journal Articles: Pathology and Microbiology

Background: Environmental lipopolysaccharide (LPS) and microbial component-enriched organic dusts cause significant lung disease. These environmental exposures induce the recruitment and activation of distinct lung monocyte/macrophage subpopulations involved in disease pathogenesis. Aconitate decarboxylase 1 (Acod1) was one of the most upregulated genes following LPS (vs. saline)exposure of murine whole lungs with transcriptomic profiling of sorted lung monocyte/macrophage subpopulations also highlighting its significance. Given monocyte/macrophage activation can be tightly linked to metabolism, the objective of these studies was to determine the role of the immunometabolic regulator ACOD1 inenvironmentalexposure-induced lung inflammation.

Methods: Wild-type (WT) mice were intratracheally (i.t.) instilled with 10 …

The Impact Of Local Physiology On The Corrosion Of Orthopedic Alloys, Madison Nicole Brown

Theses and Dissertations (ETD)

Introduction. Total knee arthroplasty (TKA) is used in the treatment of end-stage osteoarthritis of the knee. It is one of the most common elective surgeries performed with predictions expecting significant increases in the number of procedures performed over the next decade. However, the patient satisfaction rate after TKA is as low as 80%. Cobalt-chromium-molybdenum (CoCrMo) is regularly used for TKA protheses due to the alloy’s mechanical strength, biocompatibility, and corrosion resistance. The corrosion resistance of this alloy relies on a passive oxide layer. This oxide layer can be impacted by phagocytic cells which can leave pits and craters on implant …

Bacterial Single-Cell Rna Sequencing Captures Biofilm Transcriptional Heterogeneity And Differential Responses To Immune Pressure, Lee E. Korshoj, Tammy Kielian

Journal Articles: Pathology and Microbiology

Biofilm formation is an important mechanism of survival and persistence for many bacterial pathogens. These multicellular communities contain subpopulations of cells that display metabolic and transcriptional diversity along with recalcitrance to antibiotics and host immune defenses. Here, we present an optimized bacterial single-cell RNA sequencing method, BaSSSh-seq, to study Staphylococcus aureus diversity during biofilm growth and transcriptional adaptations following immune cell exposure. BaSSSh-seq captures extensive transcriptional heterogeneity during biofilm compared to planktonic growth. We quantify and visualize transcriptional regulatory networks across heterogeneous biofilm subpopulations and identify gene sets that are associated with a trajectory from planktonic to biofilm growth. BaSSSh-seq …

Characterization Of Sarcoidosis At A Combined Rheumatology- Pulmonary Clinic, Megan Schermerhorn, Md, Julianna Desmarais, Md

Poster Presentations

No abstract provided.

Increasing The Efficacy Of Actinomycin D With Resveratrol In Aerodigestive Tract Cancers, Lukmon Morenikeji Raji

Theses, Dissertations and Capstones

Chemotherapy poses a significant challenge for cancer patients due to drug-associated toxicity, which often results from their effects on both healthy (normal) and cancerous cells. While various options aim to reduce toxicity and optimize beneficial effects, a comprehensive solution remains elusive. Cyclotherapy is one such approach developed to protect normal cells from the toxic effects of chemotherapy drugs. The basic principle underlying cyclotherapy is p53- dependent cell cycle arrest of normal cells while killing cancer cells via a p53-independent mechanism using a second drug. In our research, we investigated the inhibitory effects of a combination of two low-dose anticancer drugs, …

Dual Gallium Drug Treatment Against Carbapenem-Resistant Klebsiella Pneumoniae: Efficacy And Potential Mechanism(S) Of Action And Resistance, Zachary Scott, Seoung-Ryoung Choi, Bradley E. Britigan, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

Klebsiella pneumoniae (KLP) is a Gram-negative pathogen that can be highly antibiotic-resistant. Our group has worked with gallium-based compounds as a means of treating bacterial infections. Here the possible mechanism is investigated for dual therapy comprised of gallium nitrate (Ga(NO₃)₃) and gallium protoporphyrin (GaPP) on KLP. It is found that in vitro the combination of Ga(NO₃)₃ and GaPP is synergistic against KLP. The in vivo efficacy is of the dual therapy is additionally tested by treating pulmonary KLP infections in mice. Much greater effectiveness are observed in bacterial clearance and survival of mice …

Pharmacokinetic-Pharmacodynamic Evidence From A Phase 3 Trial To Support Flat-Dosing Of Rifampicin For Tuberculosis, Huy X. Ngo, Ava Y. Xu, Gustavo E. Velásquez, Nan Zhang, Vincent K. Chang, Ekaterina V. Kurbatova, William C. Whitworth, Erin Sizemore, Kia Bryant, Wendy Carr, Marc Weiner, Kelly E. Dooley, Melissa Engle, Susan E. Dorman, Payam Nahid, Susan Swindells, Richard E. Chaisson, Pheona Nsubuga, Madeleine Lourens, Rodney Dawson, Radojka M. Savic

Journal Articles: Infectious Diseases

BACKGROUND: The optimal dosing strategy for rifampicin in treating drug-susceptible tuberculosis (TB) is still highly debated. In the phase 3 clinical trial Study 31/ACTG 5349 (NCT02410772), all participants in the control regimen arm received 600 mg rifampicin daily as a flat dose. Here, we evaluated relationships between rifampicin exposure and efficacy and safety outcomes.

METHODS: We analyzed rifampicin concentration time profiles using population nonlinear mixed-effects models. We compared simulated rifampicin exposure from flat- and weight-banded dosing. We evaluated the effect of rifampicin exposure on stable culture conversion at 6 months; TB-related unfavorable outcomes at 9, 12, and 18 months using …

The Benefits Of Medical Tetrahydrocannabinol On Glaucoma, Hunter Kane

Theses, Dissertations and Capstones

Introduction: This paper explores the potential therapeutic benefits of medical Tetrahydrocannabinol (THC) on glaucoma management, particularly in terms of intraocular pressure (IOP) reduction, ocular blood flow, and symptom management. Glaucoma, characterized by increased IOP and progressive optic nerve damage, is a leading cause of irreversible blindness. Current treatments focus on IOP control but may have inadequate efficacy or intolerable side effects, necessitating alternative approaches such as medical THC.

Methods: The study hypothesis posited that medical THC could significantly reduce IOP, enhance ocular blood flow, and improve symptom management in glaucoma patients. To test this hypothesis, a literature review supplemented by …

Hypothyroid: New Insights On An Old Disease, Sara Ward

Graduate Research Projects

No abstract provided.

Digital Clock Drawing As An Alzheimer's Disease Susceptibility Biomarker: Associations With Genetic Risk Score And Apoe In Older Adults, L I Thompson, M Cummings, S Emrani, David J. Libon, A Ang, C Karjadi, R Au, C Liu

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia in older adults, but most people are not diagnosed until significant neuronal loss has likely occurred along with a decline in cognition. Non-invasive and cost-effective digital biomarkers for AD have the potential to improve early detection.

OBJECTIVE: We examined the validity of DCTclockTM (a digitized clock drawing task) as an AD susceptibility biomarker.

DESIGN: We used two primary independent variables, Apolipoprotein E (APOE) ε4 allele carrier status and polygenic risk score (PRS). We examined APOE and PRS associations with DCTclockTM composite scores as dependent measures.

SETTING: We used existing data …

Safety And Efficacy Of Peptide Receptor Radionuclide Therapy In Neuroendocrine Tumors: A Single Center Experience., Vineeth Sukrithan, Heather Armbruster, Sherise Rogers, Sherry Mori Vogt, Cassandra Grenade, Claire Verschraegen, Ye Zhou, Ashima Goyal, Mona Natwa, Akram Hussein, Hallie Barr, Dramane Konate, Rochelle Batdorf, Andrew Brown, Bonnie Williams, Songzhu Zhao, Lai Wei, Menglin Xu, Manisha H Shah, Bhavana Konda

Oncology Articles

Peptide receptor radionucleotide therapy (PRRT) with 177Lu-dotatate is widely used for the treatment of patients with neuroendocrine tumors (NETs). We analyzed data from 104 patients with NETs treated with 177Lu -dotatate at a US academic center between December 2017 and October 2020 to better understand patterns of long-term efficacy, safety, and toxicity in the real-world setting. 177Lu-dotatate (200 mCi) was administered every eight weeks for four doses. The most common sites of primary disease were small intestine NETs (n = 49, 47%), pancreatic NETs (n = 32, 31%), and lung NETs (n = 7, 7%). Twenty-seven percent had Ki-6720%. The …

Inflammatory Protein Elicitation In Response To Whole-Body Vibration Exposure, Nicholas Miller

Theses, Dissertations and Capstones

This study aimed to assess the effects of whole-body vibration (WBV) on the brain through changes in blood protein concentrations, seat and head accelerations, and symptomatology over time. Subjects were assigned to control, 1-hour, or 8-hour vibration exposure groups. Glial fibrillary acidic protein (GFAP) and S100B concentrations were measured. Root mean square average weighted vibration (A_ws), vibration dose value (VDV), and seat-to-head transmissibility (STHT) were calculated. There were no differences in GFAP (p = 0.79) or S100B (p = 0.97) concentrations between 1-hour and 8-hour subjects (p = 0.79). Average weighted head acceleration (p …

Cancer Care Annual Report 2022-2023, Children's Mercy Kansas City

Cancer Center Annual Reports

Annual report of cancer care and oncology services at the Children's Mercy Kansas City, a pediatric medical center. This year’s report focuses on Brain Tumors.

Neonatal Abstinence Signs During Treatment: Trajectory, Resurgence And Heterogeneity, Jennifer S. Miller, Henrietta S. Bada, Philip M. Westgate, Thitinart Sithisarn, Markos Leggas

Pediatrics Faculty Publications

Neonatal abstinence syndrome (NAS) presents with a varying severity of withdrawal signs and length of treatment (LOT). We examined the course and relevance of each of the NAS withdrawal signs during treatment in a sample of 182 infants with any prenatal opioid exposure, gestational age ≥ 35 weeks, without other medical conditions, and meeting the criteria for pharmacological treatment. Infants were monitored using the Finnegan Neonatal Abstinence Scoring Tool. Daily mean Finnegan scores were estimated using linear mixed models with random subject effects to account for repeated withdrawal scores from the same subject. Daily item prevalence was estimated using generalized …

Research Annual Report Fy2024, Children's Mercy Kansas City

Research Annual Reports

Annual report of the research at Children's Mercy Kansas City in Kansas City MO, a pediatric medical center.

Drug Reaction With Eosinophilia And Systemic Symptoms (Dress) Syndrome: Lamotrigine Associated, Kendal Allen, Jordan Steelquist, Renee Delos Angeles, He Wang, Andrew Chen

Far West Division GME Research Day 2024

No abstract provided.

Cytochrome P450 Alterations In A Patient Treated With Guselkumab For Moderate-Severe Plaque Psoriasis, Michelle Militello, Sarah Ferrer-Bruker

South Atlantic Division GME Research Day 2024

No abstract provided.

Spinal Pilomyxoid Astrocytoma In A 17-Month-Old Twin, Gul Emek Wymer, Chamyan Gabriel, Robert Bender, Susana Ferra

East Florida Division GME Research Day 2024

Introduction: A pilomyxoid astrocytoma is a rare type of brain tumor that primarily affects young children, typically arising in the hypothalamic-suprasellar region of the brain. Unlike pilocytic astrocytoma, PMA is characterized by a more aggressive clinical course and distinct histopathological features, including a monomorphic cell population, angiocentric arrangement, and a myxoid background.

Case presentation: A 17 months old patient with a history of twin to twin transfusion was brought to the hospital with a complaint of motor regression, compared to his twin. The CT and MRI images revealed an intradural intramedullary spinal mass. The mass tissue biopsy was sent to …

Hormone Replacement Therapy In Adult Women As A Treatment Adjunct For Psychosis: A Literature Review, Parker Stocking, Lucille Schiffman, Lindsay Wallace, Caitlin Aquino, Cody Teleki

Continental, MidAmerica, & Mountain Divisions GME Research Day 2024

No abstract provided.

A Unique Case Of Darier's Disease With Perioral Cutaneous Cobblestoning Treated With Dupilumab, Sara Holt, Sherlyn Saju, Richard Miller

West Florida Division GME Research Day 2024

No abstract provided.

Retropharyngeal Abscess Or Malignancy? A Difficult Differential Diagnosis In New Neck Masses, Mary Therese Thomas, Brooke Reese, Mary Carter

South Atlantic Division GME Research Day 2024

No abstract provided.

Proving Pyoderma, Diagnosis And Treatment Of Suspected Pyoderma Gangrenosum, Samuel Milam, Sean Gibbs

South Atlantic Division GME Research Day 2024

No abstract provided.

Papillary Thyroid Carcinoma Of The Ovary Presenting As A Dermoid Cyst, Renee Ricci, Alicia Farris, Dina Linfoot, Maclaren Durkee, Kenley Tyler

South Atlantic Division GME Research Day 2024

No abstract provided.

Stevens-Johnson Syndrome And Pemphigus Vulgaris: A Missed Connection, Amelia Mellor, Suresh Antony

Central & West Texas GME Research Day 2024

No abstract provided.

Primary Care Physician Trust: The Importance Of Early Medical Intervention For African American Children With Asthma, Harrish Ganesh

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Asthma is a prevalent condition characterized by an individual’s airway becoming inflamed, constricted, and leads to the formation of mucus and difficulty breathing. Nearly 27 million individuals are currently diagnosed with Asthma in the United States, and African Americans are 40% more likely to be diagnosed with asthma than Caucasians. This literature review analyzed multifaceted barriers that restrict African American asthmatic children from gaining consistent asthma treatment. Some of these barriers range from historical racial discrimination that leads to parental mistrust to financial and educational barriers that result in inconsistent pediatric care for asthmatic children. The combination of the above …

Relationship Between Genotype And Disease Phenotype For Gluten-Related Disorders, Michael Roberts, Nadine Grzeskowiak, Stephen Bricher

Faculty Publications

We investigated gluten-related disorders (GRD) in intestinal biopsy-proven subjects to determine the relation between genotype (i.e., Human Leukocyte Antigen (HLA) DQ alleles) and phenotype (i.e., antibody levels and clearly defined symptoms). Subjects had known DQ genotypes, information on IgA anti-Endomysial antibodies (EMA) and/or anti-tissue Trans Glutaminase (tTG) antibodies (tTGA). Subjects also answered a survey characterizing gastrointestinal, skin, and neural symptoms. Though all were biopsy-proven, HLA genotypes included all combinations of DQ2.5, DQ2.2, DQ8, DQ7.5, DQ5, and DQ6. Subject antibody levels were proportional to the number of DQ2.5 haplotypes, and subjects with non-CD-associated haplotypes did not have positive antibody scores (despite …

Single-Cell Profiling Reveals A Conserved Role For Hypoxia-Inducible Factor Signaling During Human Craniotomy Infection, Zachary Van Roy, Gunjan Kak, Lee E. Korshoj, Joseph P. Menousek, Cortney E. Heim, Rachel W. Fallet, James Campbell, Carol Reynolds Geary, Bo Liu, Santhi Gorantla, Larisa Y Poluektova, Bin Duan, Walter S. Campbell, William Thorell, Tammy Kielian

Journal Articles: Pathology and Microbiology

Neurosurgeries complicated by infection are associated with prolonged treatment and significant morbidity. Craniotomy is a common neurosurgical procedure; however, the cellular and molecular signatures associated with craniotomy infection in human subjects are unknown. A retrospective study of over 2,500 craniotomies reveals diverse patient demographics, pathogen identity, and surgical landscapes associated with infection. Leukocyte profiling in patient tissues from craniotomy infection characterizes a predominance of granulocytic myeloid-derived suppressor cells that may arise from transmigrated blood neutrophils, based on single-cell RNA sequencing (scRNA-seq) trajectory analysis. Single-cell transcriptomic analysis identifies metabolic shifts in tissue leukocytes, including a conserved hypoxia-inducible factor (HIF) signature. The …

Glioblastoma Standard Of Care: Effects On Tumor Evolution And Reverse Translation In Preclinical Models, Louis Rodgers, John L. Villano, Anika M. S. Hartz, Björn Bauer

UK CARES Faculty Publications

Glioblastoma (GBM) presents a significant public health challenge as the deadliest and most common malignant brain tumor in adults. Despite standard-of-care treatment, which includes surgery, radiation, and chemotherapy, mortality rates are high, underscoring the critical need for advancing GBM therapy. Over the past two decades, numerous clinical trials have been performed, yet only a small fraction demonstrated a benefit, raising concerns about the predictability of current preclinical models. Traditionally, preclinical studies utilize treatment-naïve tumors, failing to model the clinical scenario where patients undergo standard-of-care treatment prior to recurrence. Recurrent GBM generally exhibits distinct molecular alterations influenced by treatment selection pressures. …

Cancer Research Provides A Model For Advancing Clinical Trials In Dementia In The Era Of Disease-Modifying Alzheimer’S-Type Dementia Therapies, Gregory Jicha, Thomas Tucker, Susanne Arnold, Peter T. Nelson

Neurology Faculty Publications

Dementia and cancer are multifactorial, widely-feared, age-associated clinical syndromes that are increasing in prevalence. There have been major breakthroughs in clinical cancer research leading to some effective treatments, whereas the field of dementia has achieved comparatively limited success in clinical research. The lessons of cancer research may help those in the dementia research field in confronting some of the dilemmas faced when the clinical care regimen is not entirely safe or efficacious. Cancer clinical trials have assumed that untreated individuals with cancer are at high risk for morbidity and mortality after primary diagnoses. Thus, patients deserve a choice of clinical …

Multiomics Analysis To Explore Blood Metabolite Biomarkers In An Alzheimer’S Disease Neuroimaging Initiative Cohort, Takaki Oka, Yuki Matsuzawa, Momoka Tsuneyoshi, Yoshitaka Nakamura, Ken Aoshima, Hiroshi Tsugawa, Alzheimer’S Disease Metabolomics Consortium

Neurology Faculty Publications

Alzheimer’s disease (AD) is a neurodegenerative disease that commonly causes dementia. Identifying biomarkers for the early detection of AD is an emerging need, as brain dysfunction begins two decades before the onset of clinical symptoms. To this end, we reanalyzed untargeted metabolomic mass spectrometry data from 905 patients enrolled in the AD Neuroimaging Initiative (ADNI) cohort using MS-DIAL, with 1,304,633 spectra of 39,108 unique biomolecules. Metabolic profiles of 93 hydrophilic metabolites were determined. Additionally, we integrated targeted lipidomic data (4873 samples from 1524 patients) to explore candidate biomarkers for predicting progressive mild cognitive impairment (pMCI) in patients diagnosed with AD …