Translational Medical Research Commons^™

Glutamate Optimization As A Treatment For Depression: A Clinical Guideline, Luisa Angeles Collins Villares

Doctor of Nursing Practice (DNP) Scholarly Projects - Archive

Based on the use of drugs to treat hypertension and tuberculosis for depression, the monoamine hypothesis led to the development of antidepressants in 1952. Serotonin was recognized as a deficiency associated with depression in 1967. As a fine-tuning orchestration of neurotransmitters and neuromodulators, the glutamate system became known using Spravato in 2019 and Auvelity in 2022. In this pilot study, mental health experts rated the importance of 24 science-based recommendations to optimize glutamatergic therapy in depression for a proposed guideline on a Likert scale from zero to four. The results were analyzed using a non-parametric predictive modeling method called Chi-Square …

Modulating The Mtor Pathway Using Inducible Retrogradely Transported Aavs As A Novel Approach To Improve Motor Recovery In Spinal Cord Injury, Christopher Bosse-Joseph

Theses and Dissertations--Medical Sciences

Spinal cord injury poses multiple regeneration barriers, including neuronal-intrinsic and extrinsic factors. Overcoming these barriers has stood as a longstanding challenge in neuroscience. A well-studied mechanism to promote spinal cord regeneration and locomotor recovery is activating the PI3K/mTOR pathway by knocking out phosphatase and tensin homolog protein (PTEN). PTEN knockout (PTEN-KO) studies have traditionally used adeno-associated virus (AAV) viral vectors to improve functional recovery. The use of traditional AAV serotypes to induce PTEN-KO has shown promise to improve functional recovery in rodent models; however, these approaches show significant limitations for translational utility. Firstly, the use of traditional AAV serotypes to …

Developing Radiosensitizers To Enhance Radiotherapy In Treating Gastroenteropancreatic Neuroendocrine Tumor, Zeta Chow

Theses and Dissertations--Clinical and Translational Science

Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET) is a heterogeneous group of malignancies arising from multipotent neuroendocrine stem cells in the gastrointestinal tract. The incidence of GEP-NET continues to rise, possibly due to the advancement of imaging and biomarkers available for diagnosis. However, even though the majority of patients are diagnosed with low-grade and localized disease, a significant percentage of patients present with advanced-stage metastatic disease with poor prognosis in months to a few years. These advanced-stage GEP-NET patients can also present with a variety of debilitating symptoms that significantly impact their quality of life. The role of palliative-intent surgery is limited, and …

Examining Occupation-Based Outcome Measure Use In A Neurologic Outpatient Occupational Therapy Setting: A Knowledge Translation Initiative, Elizabeth Yost, Suzanne Trojanowski, Taylor Jarnigin, Kevin De Bear, Amy Yorke

Translational Science in Occupation

Abstract

Importance: Occupation-based outcome measures (OBOMs) are an evidence-based recommendation for occupational therapy evaluations. Knowledge translation (KT) is a process used to help integrate evidence into clinical practice. The authors identified a KT opportunity to examine occupational therapy practitioners’ (OTPs) use of outcome measures in an outpatient practice setting and assess a Know-Do Gap as the first step in the Action phase of a KT initiative.

Objective: Describe the frequency and types of outcome measures documented in occupational therapy (OT) evaluations, with a focus on OBOMs.

Design: Cross-sectional descriptive study.

Setting: Three outpatient clinic sites (under one parent company) in …

Analysis Of The Immune Response After Readministration Of A Novel Aav6 Gene Therapy Containing Tlr9 Inhibitory Sequences, Sarah Elysse Allen

MUSC Theses and Dissertations

Therapeutic options for the treatment of Surfactant Protein-B (SP-B) deficiency, an autosomal recessive disorder that leads to fatal respiratory distress, are extremely limited with the exception of double lung transplantation. One method for treating this monogenic lung disease is with adeno-associated virus (AAV) gene therapy treatment that delivers the hSFTPB transgene into the lungs. The transient nature of AAV transgene expression led to a need for sustained gene expression, which could possibly be achieved through redosing. The main obstacle with redosing is the innate immune response and subsequent inflammatory response pathways that are activated after recognition of unmethylated CpG motifs …

Novel Engineering Approaches For Orthopedic Injury Treatment And Infection Diagnosis, Cynthia Co

Bioengineering Dissertations - Archive

Bioengineering has made significant contributions to the treatment of orthopedic injury through interdisciplinary approaches. Central to these advancements are many orthopedic implants, including anchors and joint replacements, which have been designed to restore mobility. Despite their functional efficacy, these products have limited lifespan and are associated with many complications, such as implant-associated infection. The success of implant design and function, both in the short and long term, is paramount for enhancing patient outcomes and overall well-being. Therefore, my thesis work is dedicated to addressing these critical challenges, aiming to maximize their treatment effect while minimizing the implant-associated complications.

Long-term patient …

The Enact Network Is Acting On Housing Instability And The Unhoused Using The Open Health Natural Language Processing Toolkit, Daniel R Harris, Sunyang Fu, Andrew Wen, Alexandria Corbeau, Darren Henderson, Jordan Hilsman, David Oniani, Yanshan Wang

Faculty, Staff and Student Publications

Housing is an environmental social determinant of health that is linked to mortality and clinical outcomes. We developed a lexicon of housing-related concepts and rule-based natural language processing methods for identifying these housing-related concepts within clinical text. We piloted our methods on several test cohorts: a synthetic cohort generated by ChatGPT for initial infrastructure testing, a cohort with substance use disorders (SUD), and a cohort diagnosed with problems related to housing and economic circumstances (HEC). Our methods successfully identified housing concepts in our ChatGPT notes (recall = 1.0, precision = 1.0), our SUD population (recall = 0.9798, precision = 0.9898), …

Evaluation Of Silk Fibroin And Hylauronic Acid As Otic Drug Delivery System Additives; Investigation Of Silk Fibroins Responses To Enviromental Stimulii, Kolton Charles Sandau

Graduate Student Theses, Dissertations, & Professional Papers

The Serban lab has previously developed and reported on a single application drug delivery system for the treatment of otitis externa. Otitis externa also known as outer ear infections is a very common ailment that impacts large portions of both human and domestic animal populations. Typical treatment for otitis externa typically requires an extended dosing regimen over several days that is inconvenient and can lead to poor clinical outcomes due to poor patient compliance. Our delivery system employs a thixotropic gel to deliver a steady dose of medication over the duration of the infection.

Here we evaluated the reproducibility and …

Tim/Tam Receptors: A Potential Biomarker For Predicting Sensitivity To Zika Virus-Induced Oncolysis In Non-Small Cell Lung Cancers, Shankari Somasekar

Honors Undergraduate Theses

Non-small cell lung cancers (NSCLC) constitute 80-85% of lung cancers and are the leading cause of cancer-related deaths globally. The most common cause is prolonged smoking. Current treatment options for NSCLC include surgery, radiation, chemotherapy, targeted drug therapy, and immunotherapy. Although these medications are effective in the short term, patients often face issues of drug resistance and debilitating side effects with prolonged use. Currently, the use of Zika virus (ZIKV) is being researched as a possible alternative treatment for cancer, which minimizes side effects and the risk of drug resistance. TIM/TAM proteins are identified as the putative ZIKV receptors on …

Effects Of Huoxue Qufeng Decoction Combined With Tongguan Liquefying Acupoint Penetration Therapy On Swallowing Function And Quality Of Life In Patients With Ischemic Stroke, Xuzhong Liang, Li Ma, Lixia Zhang, Dongnian Yang, Lanrui Zeng

Faculty, Staff and Student Publications

Objective: To analyze the effects of Huoxue Qufeng Decoction combined with Tongguan Liquefying Acupoint Penetration therapy on swallowing function and quality of life in patients with ischemic stroke.

Methods: A total of 145 patients with post-stroke dysphagia admitted to Dingxi People's Hospital from January 2019 to May 2022 were selected with 65 patients in the control group and 80 patients in the observation group. The control group received Huoxue Qufeng Decoction alone, while the observation group received additional Tongguan Liquefying Acupoint Penetration therapy. Clinical efficacy, NIH Stroke Scale (NIHSS) score, Water Swallow Test, Swallowing Function Assessment (SSA) score, MD Anderson …

Characterizing Treatment Non-Responders And Responders In Completed Alzheimer's Disease Clinical Trials, Dulin Wang, Yaobin Ling, Kristofer Harris, Paul E Schulz, Xiaoqian Jiang, Yejin Kim

Faculty, Staff and Student Publications

Characterizing differential responses to Alzheimer's disease (AD) drugs will provide better insights into personalized treatment strategies. Our study aims to identify heterogeneous treatment effects and pre-treatment features that moderate the treatment effect of Galantamine, Bapineuzumab, and Semagacestat from completed trial data. The causal forest method can capture heterogeneity in treatment responses. We applied causal forest modeling to estimate the treatment effect and identify efficacy moderators in each trial. We found several patient's pretreatment conditions that determined treatment efficacy. For example, in Galantamine trials, whole brain volume (1092.54 vs. 1060.67 ml, P < .001) and right hippocampal volume (2.43e-3 vs. 2.79e-3, P < .001) are significantly different between responsive and non-responsive subgroups. Overall, our implementation of causal forests in AD clinical trials reveals the heterogeneous treatment effects and different moderators for AD drug responses, highlighting promising personalized treatment based on patient-specific characteristics in AD research and drug development.

Diet-Stimulated Marrow Adiposity Fails To Worsen Early, Age-Related Bone Loss, Cody Mcgrath, Sarah E Little-Letsinger, Gabriel M Pagnotti, Buer Sen, Zhihui Xie, Gunes Uzer, Guniz B Uzer, Xiaopeng Zong, Martin A Styner, Janet Rubin, Maya Styner

Faculty, Staff and Student Publications

Introduction: Longitudinal effect of diet-induced obesity on bone is uncertain. Prior work showed both no effect and a decrement in bone density or quality when obesity begins prior to skeletal maturity. We aimed to quantify long-term effects of obesity on bone and bone marrow adipose tissue (BMAT) in adulthood.

Methods: Skeletally mature, female C57BL/6 mice (n = 70) aged 12 weeks were randomly allocated to low-fat diet (LFD; 10% kcal fat; n = 30) or high-fat diet (HFD; 60% kcal fat; n = 30), with analyses at 12, 15, 18, and 24 weeks (n = 10/group). Tibial microarchitecture was analyzed …

Feasibility Of Using Podcasts For Knowledge Dissemination To Reduce Health Disparities For Women Targeting Preventative Initiatives And Lifestyle Medicine Interventions, Kristin Stovern

Doctor of Nursing Practice Scholarly Project

The purpose of this feasibility project was to look at podcasts to shed light on the issues that affect the well-being of women with gender-based disparities in healthcare. Women face persistent obstacles when it comes to the quality of healthcare they receive. One of the barriers that has been ever-present is with failure of the medical system to rigorously study the effects of diseases and drugs on women or to fund studies on women’s health conditions. Implicit biases and lack of access to care inhibit the quality of healthcare. Collectively, these issues result in unnecessary sickness, disability, and decreased quality …

Air-Jet Bioprinting Of Stem Cell-Encapsulated Alginate Micro-Droplets For Organoid Biomanufacturing, Mirabella B. Stump

Electronic Theses and Dissertations

Biomanufactured 3D-organoids show promise for modeling and treating various conditions, particularly insulin-dependent diabetes mellitus (type-1 diabetes). Pancreatic islet organoids serve as sustainable sources of insulin-producing β-cells, potentially restoring insulin regulation in patients and providing a long-term solution for diabetes. Hydrogel droplet printing is an emerging technique in regenerative medicine due to its advantageous tunability and biocompatibility; however, challenges of consistency, quality control, and scalability persist. To address these issues, we developed a novel air-jetting based droplet bioprinting system for the generation of monodispersed alginate micro-droplets. The objective of this project was to incorporate human induced pluripotent stem cells (hiPSCs) into …

Pkcε Activator Protects Hippocampal Microvascular Disruption And Memory Defect In 3×Tg-Alzheimer's Disease Mice With Cerebral Microinfarcts, Huaixing Wang, Zongxiu Zhang, Jarin Hongpaisan

Center for Translational Medicine Faculty Papers

BACKGROUND: Current evidence suggests that microvessel disease is involved in Alzheimer's disease (AD). Cerebrovascular disease correlates with cardiovascular disease and is complicated in ≈40% of AD patients. The protein kinase C (PKC) ε activator DCPLA can stimulate human antigen (Hu) R that prevents degradation and promotes the translation of mitochondrial Mn-superoxide dismutase (MnSOD) and vascular endothelial growth factor-A (VEGF) mRNAs.

METHODS: To induce brain microinfarcts, we injected triple transgenic (3×Tg) and wild-type (WT) control mice with microbeads (20 μm caliber) into common carotid arteries, with or without the DCPLA-ME (methyl-ester) for 2 weeks. After water maze training, mice at 16 …

Interleukin 31 Receptor Α Promotes Smooth Muscle Cell Contraction And Airway Hyperresponsiveness In Asthma, Santhoshi Akkenepally, Dan Yombo, Sanjana Yerubandi, Geereddy Bhanuprakash Reddy, Deepak Deshpande, Francis Mccormack, Satish Madala

Center for Translational Medicine Faculty Papers

Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness (AHR), inflammation, and goblet cell hyperplasia. Multiple cytokines, including IFNγ, IL-4, and IL-13 are associated with asthma; however, the mechanisms underlying the effects of these cytokines remain unclear. Here, we report a significant increase in the expression of IL-31RA, but not its cognate ligand IL-31, in mouse models of allergic asthma. In support of this, IFNγ, IL-4, and IL-13 upregulated IL-31RA but not IL-31 in both human and mice primary airway smooth muscle cells (ASMC) isolated from the airways of murine and human lungs. Importantly, the loss of IL-31RA …

Translational Research Targeting Biliary Tract Cancer, Yan Zhu

Dissertations and Theses (Open Access)

Biliary tract cancer (BTC) is malignant tumor that originates from the biliary tract, including cholangiocarcinoma (CCA) and gallbladder cancer (GBC). In this translational research program targeting BTC, we focus on three aspects: the development of a combination treatment against CCA, the exploration of the immune background of GBC, and the establishment of a CCA mouse model mimicking mutation profiles of CCA patients.

Patients with cholangiocarcinoma have poor clinical outcomes due to late diagnoses, poor prognoses, and limited treatment strategies. To identify novel drug combinations for this disease, we have conducted a genome wide CRISPR screen anchored on the bromodomain and …

Reactive Oxygen Species Behaving Badly: Oxidized Phosphatidylcholines Corrupt Ca2+ Signaling In Airway Smooth Muscle, Deepak A. Deshpande, Raymond B. Penn

Center for Translational Medicine Faculty Papers

No abstract provided.

Breast Cancer In Pms2 Related Lynch Syndrome: Evidence Of A Possible Association?, Ujjwal Karki, Tara Rangarajan, Dana Zakalik

Conference Presentation Abstracts

Background: Lynch syndrome (LS) is a hereditary cancer predisposition syndrome caused by pathogenic variants (PVs) in mismatch repair genes, MLH1, MSH2, MSH6, and PMS2. LS is associated with increased risk of colorectal, and endometrial cancers but breast cancer risk is uncertain, with some studies suggesting MSH6 and PMS2 PVs may have a higher risk for breast cancer. Our study outlines the incidence and clinical characteristics of breast cancer in PMS2-related LS identified at a large academic center. Methods: Patients with PMS2 PVs identified between July 2009 and May 2023 were selected from a database at the Nancy and James Grosfeld …

Characteristics Of Breast Cancer In Carriers Of Pathogenic Variant In Atm In A Large Academic Health Center, Ujjwal Karki, Tara Rangarajan, Dana Zakalik

Conference Presentation Abstracts

Background: Pathogenic variants (PVs) in ATM are associated with an increased risk of breast, pancreas, and other cancers. The clinical and pathological characteristics of ATM-associated breast cancers have not been well defined. Methods: Patients who underwent multigene panel testing between December 2012 and May 2023 and were identified to harbor ATM PVs were included in the study. We analyzed demographics, germline findings, histopathology, genomic recurrence score, and management of ATM PV carriers with breast cancer. Results: A total of 222 individuals were identified to have PVs in ATM, of whom 184 (83%) were female. The majority were Caucasian (n = …