Translational Medical Research Commons^™

Editorial: Advancing Musculoskeletal Health: Bridging Basic And Clinical Research On Biomechanical Properties Of Joints, Ligaments, Tendons, And Associated Structures, Xin Jin, Snehal S. Shetye, Mengcun Chen

Center for Translational Medicine Faculty Papers

No abstract provided.

Synergistic Anti-Tumor Activity Of Ciclopirox Olamine And Metformin In Triple-Negative Breast Cancer, Yakun Wu, Hui Lyu, Congcong Tan, Margaret E. Larsen, Shou Ching Tang, Shile Huang, Bolin Liu

School of Graduate Studies Faculty Publications

No abstract provided.

Volumetric Wear Analysis Of Polyethylene Orthopedic Liners Using Point Clouds, Gabriel Landi

Dartmouth College Master’s Theses

In vivo wear of ultra-high molecular weight polyethylene (UHMWPE) orthopedic bearings represents a major problem in shoulder and knee arthroplasty, with significant amounts of devices failing due to the complication itself, and even more due to associated reasons for retrieval, including aseptic loosening. However, quantification of UHMWPE wear has largely been limited to linear and in vitro volumetric analyses, obscuring the understanding of the amount of clinically relevant material loss. This study proposes new methods to measure articular, rim, and backside surfaces of retrieved shoulder and knee UHMWPE liners, centered around the coordinate measuring machine (CMM)-based collection of high density …

The Functional Significance Of Plk1 Phosphorylation Of Nrf2 In Prostate Cancer Progression, Maria Nur

Theses and Dissertations--Toxicology and Cancer Biology

Prostate cancer progression and therapeutic resistance are closely linked to alterations in redox homeostasis and cell cycle regulation. Nuclear factor erythroid 2–related factor 2 (NRF2) is a master regulator of antioxidant responses, yet the mechanisms integrating cell cycle signaling with NRF2 activity in prostate cancer remain poorly defined. In this study, we identify polo‑like kinase 1 (PLK1) as a novel regulator of NRF2 through direct phosphorylation at serine 253 (S253). Using bioinformatic prediction, mass spectrometry, in vitro kinase assays, and cell‑based analyses, we demonstrate that PLK1 phosphorylates NRF2 at S253 in a cell cycle–dependent manner, with maximal phosphorylation during mitosis. …

Biomechanical Effects Of Exercise-Based Interventions In Chronic Nonspecific Low Back Pain: A Systematic Review And Meta-Analysis, Lara De Vecchi Machado

Theses and Dissertations--Kinesiology and Health Promotion

Chronic nonspecific low back pain (CNLBP) is the leading cause of years lived with disability worldwide and represents a complex, multifactorial, and heterogeneous condition. It is characterized by substantial interindividual variability in muscle activation patterns, lumbo-pelvic coordination, and movement strategies. Although exercise is widely recommended as a first-line intervention and its clinical benefits are well established, the biomechanical mechanisms underlying functional improvement remain fragmented in the literature and are rarely synthesized quantitatively.

This dissertation conducted a systematic review with meta-analysis to investigate the biomechanical effects of exercise-based interventions in individuals with CNLBP. A total of 39 studies were included and …

The Immune Hangover: Understanding The Influence Of Alcohol Use, Abstinence, And Post-Abstinence Drinking On Monocyte Plasticity, Madison B. Blanton

Theses and Dissertations--Pharmacy

Alcohol consumption is widespread in the United States, with 80% of individuals aged 12 and older reporting alcohol use and 1-in-4 engaging in risky drinking behaviors. Alcohol misuse heightens susceptibility to infections and delays wound healing, indicating a disrupted immune system. Previous studies show alcohol rewires immune cells, especially monocytes and macrophages, which play critical roles in tissue homeostasis and host defense.

Using a rhesus macaque model of ethanol self-administration, we demonstrate that after 6-months of drinking, monocytes exhibit decreased cytokine production and significant transcriptomic changes, indicating a hypo-inflammatory state. In contrast, 12-months of chronic alcohol use induces hyperinflammatory responses, …

Synthesis And Characterization Of Glass-Ceramic Nanoparticles And Nanobubbles For Integration Into Bone Regenerative Biomaterials, Sun Latt

Honors Undergraduate Theses

Osteoporosis affects over 200 million individuals worldwide and is characterized by an imbalance between osteoclastic bone resorption and osteoblastic bone formation, leading to fragility fractures that significantly diminish quality of life. Current clinical bone cements, such as poly(methyl methacrylate), are limited by poor osseointegration, toxic monomers, and an inability to address the underlying pathophysiology of osteoporosis. This work presents the synthesis, characterization, and systematic in vitro evaluation of a sol-gel-derived, magnesium-incorporated glass-ceramic (GC) nanoparticle within the CaO-MgO-SiO₂ system for incorporation into a novel hydrogel bone cement and bioresorbable magnesium implants. XRD confirmed a biphasic amorphous-crystalline diopside composition, and TEM …

Oral Pathogens Reprogram Endothelial Barrier And Angiotensin-Converting Enzyme2/Endothelial Nitric Oxide Synthase-Nitric Oxide Signaling To Promote Blood Pressure Dysregulation, Ming-Shou Hsieh, Tung-Nien Hsu, Chin-Sheng Huang, Ting-Yi Renn, Kuang-Tai Kuo, Kuo-Yao Lin, Wei Jen Chang

Journal of Dental Sciences

Background/purpose: Although periodontal disease is associated with an increased risk of hypertension, the endothelial mechanisms linking oral inflammation to vascular dysfunction remain unclear. We investigated whether Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) can directly disturb endothelial homeostasis and whether macrophage–endothelial crosstalk further worsens endothelial injury.

Materials and methods: Human umbilical vein endothelial cells (HUVECs) were exposed to Pg-LPS alone or co-cultured (transwell system) with Pg-LPS-primed human monocytic cells -derived macrophages. Endothelial dysfunction was assessed through nitric oxide (NO) production, endothelial nitric oxide synthase (eNOS) phosphorylation, inflammatory and adhesion molecule expression, as well as junctional and cytoskeletal changes. Macrophage …

A Chicken Model For Non-Invasive Diagnosis Of Infant Developmental Dysplasia Of The Hip (Ddh) Using Acoustic Transmission Measurements, Aliza Shah

Honors Undergraduate Theses

Developmental dysplasia of the hip (DDH) is a condition characterized by abnormal development and stability of the hip joint. In a healthy infant, the femoral head (ball) fits securely within the acetabulum (socket of the pelvis), allowing for proper joint function. In DDH, the relationship is disrupted, ranging from mild acetabular dysplasia to partial (subluxation) or complete dislocation of the femoral head. This condition represents a range of structural abnormalities that develop during early growth. The integrity of the hip joint is essential for physical mobility, and disruption of this structure can lead to significant functional impairment. DDH may result …

Use Of Transcranial Magnetic Stimulation As An Assessment Of Corticospinal Excitability In Individuals With Persistent Postural Perceptual Dizziness, Elizabeth Cornforth

Theses and Dissertations

Persistent postural-perceptual dizziness (PPPD) is a common, disabling, chronic vestibular disorder whereby individuals experience symptoms of non-vertiginous dizziness, unsteadiness, and sway or rocking that are present most hours of the day, most days of the week. Individuals with PPPD have been noted to have an increased burden of dizziness and reduced quality of life compared to other dizziness diagnoses. The cause of PPPD is not well understood which can lead to years of diagnostic testing, failed therapies, and poor symptom management. It is important to understand PPPD pathophysiology so that optimal treatment interventions can be developed for this disorder to …

Microglial Expression Of Serotonin Receptors Reveals Parallel Regulation Of 5-Ht2b And Bdnf In The Rat Hippocampus, Andrei Turkin, Maria Sidorova, Ekaterina Kurilova, Natalia Alenina, Oksana Tuchina, Friederike Klempin

School of Graduate Studies Faculty Publications

Growing evidence suggests that psychiatric disorders are characterized by a prolonged inflammatory state, which may influence the efficacy of compounds targeting serotonin. Serotonin is a key signaling molecule in neuroplasticity of the adult hippocampus and involved in antidepressant action. Recent in vitro studies indicate the neurotransmitter may also facilitate the response to inflammation and potentially modulate microglial function towards neuroprotection. Using Tph2−/− rats depleted of brain serotonin, we examined microglial expression of various serotonin receptors (5-HTRs) in vivo in both the hippocampus and prefrontal cortex and assessed mRNA levels of cytokines and brain-derived neurotrophic factor (BDNF). We observed age-dependent and …

Protocol For Nucleo-Cytoplasmic Fractionation Of Mammalian Cells To Study Protein Translocation Via Immunoblotting, Adhikarimayum Lakhikumar Sharma, Eddy Zhu, Rithika Padyala, Kavya Parikh, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Studying protein translocation is essential for understanding protein function and regulatory mechanisms, including the activity of transcription factors. Here, we present a protocol for isolating high-quality cytoplasmic and nuclear protein fractions from mammalian cells. We describe steps for separating cytoplasmic proteins, washing nuclei, and extracting nuclear proteins. We then detail procedures for quantifying proteins and analyzing their distribution by immunoblotting within a single immunoblot. This protocol is applicable to both suspension and adherent cell types. For complete details on the use and execution of this protocol, please refer to Sharma et al.

Long Covid Incidence Across Sars-Cov-2 Lineages And Identification Of Conserved Spike Targets For Multivalent Vaccines, Grace J. Kim, Md Ashad Alam, Judy S. Crabtree, Rebecca Rose, Susanna L. Lamers, San Chu, Ronald Horswell, Daniel Fort, Lucio Miele

School of Graduate Studies Faculty Publications

Background: Long COVID remains poorly characterized at the genomic level. The primary aim of this study was to examine the relationship between viral sequences and the incidence of Long COVID at a tertiary care center in Louisiana between April 2020 and December 2022. A secondary aim was analysis of the Spike protein to identify conserved regions for multivalent vaccine targets. Method: To estimate Long COVID incidence across variants, we linked 4,789 SARS-CoV-2 sequences to 3,090 de-identified patient electronic health record information. The base population was defined as any patient with an International Classification of Diseases-10-Clinical Modification COVID-19 diagnosis code (U07.1) …

The Need To Incorporate Polysubstance Use In Neuropsychopharmacology Research: Biological Lessons And New Opportunities, Max E. Joffe, Susan M. Ferguson, Nick W. Gilpin, Melissa A. Herman, Lori A. Knackstedt, Patrick A. Randall, Abigail G. Schindler, Mary M. Torregrossa, Jennifer A. Rinker

School of Medicine Faculty Publications

Critical evaluation and refinement of animal models is essential for neuroscientists to understand complex physiological and pathological processes related to psychiatric diseases. In general, preclinical studies modeling drug dependence and problematic substance use have been limited to the administration of a single substance; however, there is a growing appreciation that this approach has failed to capture the complexities of humans and has stifled translational efforts. Polysubstance use represents the overwhelmingly common patterns of alcohol and drug use in humans. For example, epidemiological studies generally determine that between 70–95 % of individuals with alcohol use disorder use tobacco daily, and upwards …

Are E-Cigarettes A Safer Alternative? Revisiting The Cardiovascular Cost Of Nicotine Delivery, Jason D. Gardner

School of Graduate Studies Faculty Publications

No abstract provided.

Translational Research On Color Vision: From Mechanisms To Performance Enhancement In Diverse Settings, Jewearly Lundby

Theses & Dissertations

This dissertation investigated the mechanisms and applications for optimizing color vision performance across diverse contexts. In a world where color cues augment critical decisions to optimize performance and safety in transportation (e.g., aviation, railway), military, law enforcement, medical diagnostics, and myriad occupational tasks, deficiencies in color perception pose significant challenges. By uniting four interrelated studies, this work explored intrinsic retinal processes, assistive technologies for deficiencies, and novel pathways that challenge conventional understandings of vision. The research bridged fundamental vision science with applications in occupational settings, low vision rehabilitation, and clinical diagnostics, ultimately aiming to optimize color performance.

The first study …

Sik2 Inhibitor Grn-300 Enhances Sensitivity To Paclitaxel Treatment In Triple-Negative Breast Cancer, Marc A. Pina

Dissertations and Theses (Open Access)

Breast cancer is one of the most frequently diagnosed cancers worldwide, with approximately 15% classified as Triple-Negative Breast Cancer (TNBC). TNBC lacks expression of estrogen (ER) and progesterone (PR), and does not overexpress HER-2, leaving patients without effective targeted therapies. As a result, treatment primarily relies on chemotherapy, most commonly paclitaxel, a taxane that stabilize microtubules, disrupts chromosome separation and induces apoptosis. However, TNBCs are an aggressive cancer subtype, and patients often will develop resistance after a few rounds of chemotherapy. This study addresses a critical unmet need for more effective TNBC therapies by targeting Salt-Inducible Kinase 2 (SIK2), which …

Orthogonal Comparison Of Nuclear And Mitochondrial Clonal Architectures In Hematologic Malignancies, Nehali Shah

Dissertations and Theses (Open Access)

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by accumulation of mutations that disrupt hematopoietic differentiation and promote clonal expansion. Understanding how these mutations arise and evolve is essential for improving diagnosis, prognosis, and treatment stratification. Current methods are limited by either restricted genomic coverage (targeted panels) or low throughput and high cost (in single-cell whole genome sequencing, scWGS). An emerging alternative is the use of mitochondrial DNA (mtDNA) mutations as clonal markers.

This study aims to determine whether mitochondrial-derived clonal architectures correlate with nuclear-derived clonal architectures in AML, thereby evaluating mtDNA as a scalable orthogonal tool for lineage …

Acceptability Of Corticosteroid Use In The Treatment Of Infant Bronchiolitis: Utilizing The Theoretical Framework Of Acceptability To Design Research Instruments, Caroline R. Smetanka

Capstone Experience: Master of Public Health

Bronchiolitis is the leading cause of hospitalization among infants under six months, yet treatment remains largely supportive due to clinical guidelines that discourage pharmacologic intervention. Recent research suggests that bronchiolitis is not a uniform condition, and a subgroup of infants (those classified within “Profile A”) may benefit from targeted corticosteroid therapy. However, these treatments remain outside current clinical guidelines, and their successful adoption depends on stakeholder acceptability. This Capstone project developed and refined four data collection instruments- two questionnaires and two interview guides- designed to assess how healthcare providers and caregivers perceive the acceptability of corticosteroid treatment for Profile A …

Low Magnetic Fields Stimulate Cardiac Mitochondrial Bioenergetics With A Bell-Shaped Response: Possibly Via A Radical Pair Mechanism, Gisela Beutner, Huoy-Jen Yuh, Ilan Goldenberg, Douglas C. Wallace, George A. Porter, Arthur J. Moss, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

Low magnetic fields (LMFs) of less than 1 × 10 3 Tesla (T) affect numerous biological processes, including plant growth and bird migration. At a cellular level, LMFs influence intracellular Ca2+ concentrations and generation of mitochondrial reactive oxygen species (mROS). However, the mechanisms that account for these effects are controversial. Here, by applying a static LMF, ranging from ~2.7 × 10 4 to ~1.9 × 10 3 T, to mitochondria isolated from adult rat hearts, a bell-shaped increase in State 3 respiration (S3R) was observed, up to 40 %. A similar LMF-induced increase in S3R was also observed in mitochondria …

Dietary Fiber Modulates Gut Microbiota And Lipid Metabolism Ameliorating Alzheimer's Pathology In 5xfad Mice, Yuhai Zhao, Christopher M. Taylor, Walter J. Lukiw, Nicolas G. Bazan

School of Graduate Studies Faculty Publications

The gut-brain axis plays a critical role in maintaining neuronal integrity and influencing the progression of Alzheimer's disease (AD). Here, we investigated how commonly consumed dietary fibers modulate gut microbiota, lipid metabolism, and AD pathology in 5xFAD mice. Male mice were fed either fiber-free (FF) or fiber-plus (FP; 1% cellulose, 2% pectin, 2% inulin) diets for five months, followed by integrated analyses of gut microbiota (16 S rRNA sequencing), fecal lipid metabolites (LC-MS/MS), and neuropathological and behavioral outcomes. FP diets markedly altered microbial composition, characterized by increases in Muribaculaceae, Ileibacterium, and Lachnospiraceae NK4A136 group and reductions in Faecalibaculum and Coriobacteriaceae …

Diurnal Behavioral Outcomes And Bbb Integrity In Adult Male Shr And Wky Rats, Pallavi Shrivastava, Oluchukwu D. Biose, Riya Dahal, Abdallah Jwayyed, Rukayat A. Raji, Huijing Xia, Eric Lazartigues, Ifechukwude J. Biose

School of Graduate Studies Faculty Publications

Day and night neurobehavioral tests were performed for Spontaneously Hypertensive rats (SHR) and Wistar Kyoto rats (WKY) to establish an optimal testing window. Also, blood–brain barrier (BBB) integrity in brain areas related to cognition was measured to determine strain-specific differences. Six months old male SHR and WKY were randomly divided into day (i.e., 9–11 a.m.) and nighttime (i.e., 7–9 p.m.) testing regimen. Neurobehavioral tests included: Y-maze spontaneous alternation, open field, novel object recognition (NOR), and tail suspension test (TST). BBB integrity was measured in the cortex, hippocampus and striatum. WKY showed higher recognition memory at night compared to SHR and …

Hypertensive Remodelling: When Bigger Body Means Bigger Problems, Eric Lazartigues

School of Medicine Faculty Publications

No abstract provided.

Estrogen And Obesity Synergistically Suppress Protein S Via Hif1Α, Enhancing Thrombosis Potential, Mohammad A. Mohammad, Narender Kumar, Sonali Ghosh, Ashley L. Paysse, Claudia Leonardi, Vijaya Pilli, Ma Lorena Duhaylungsod, Eric Lazartigues, Diana Polania-Villanueva, Sadaf Nouman, Logan A. Barrios, Rima Chattopadhyay, Rafika Yasmin, Alaina Guilbeau, Manoj Kumar, Tina H. Nguyen, Jovanny Zabaleta, Li Li, Luis Del Valle M.D., Mallory T. Barbier, Samarpan Majumder, Laurent O. Mosnier, Samarpan Majumder

School of Graduate Studies Faculty Publications

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality, with risk heightened in premenopausal women with obesity or use estrogen-based oral contraceptives. When both risk factors are present, the thrombosis risk increases substantially. Protein S (PS), an essential anticoagulant cofactor, is downregulated by both estrogen and obesity, but the molecular basis for this suppression remains poorly defined. We investigated the effect of estrogen and obesity on PS expression using plasma samples from 157 women stratified by BMI and contraceptive use, alongside 40 mice categorized as lean or obese with or without estrogen pellet treatment. The levels of PS …

Cardiac Sr-Mitochondria Contacts-Impact On Cardiac Physiology And Mitochondrial Fitness, Celia Fernandez-Sanz, Shey-Shing Sheu, Sergio De La Fuente

Center for Translational Medicine Faculty Papers

In adult cardiomyocytes, within the Mitochondrial Associated Membranes (MAMs), the sarcoplasmic reticulum (SR) and mitochondria juxtapose each other, forming a unique and highly repetitive functional structure throughout the cells. These SR-mitochondria contact sites have emerged as critical structures that regulate various physiological processes, including lipid exchange, calcium (Ca²⁺) communication, control of excitation-contraction bioenergetics coupling, and reactive oxygen species (ROS) production. Over the years, several scientific studies have reported the accumulation of diverse proteins within these SR-mitochondria close contacts. Some proteins strategically accumulate in these areas to enhance their function, such as the mitochondrial Ca²⁺ uniporter, while others …

Her3 Promotes Triple-Negative Breast Cancer Progression By Upregulating Phf8 Via Mir-34b-5p-Dependent Mechanism, Hui Lyu, Cong Cong Tan, Yakun Wu, Margaret E. Larsen, Qingzhao Yu, Guobin Kang, Charles Wood, Shou Ching Tang, Bolin Liu

School of Graduate Studies Faculty Publications

Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, with limited targeted treatment options and poor clinical outcomes. HER3 has recently emerged as a promising therapeutic target, with HER3-directed antibody–drug conjugates advancing to Phase III clinical trials for non-small cell lung cancer. However, the downstream molecular mechanisms by which HER3 promotes TNBC progression remain poorly defined. In this study, we uncovered a previously unrecognized HER3/miR-34b-5p/PHF8 signaling axis that drives TNBC cell proliferation and tumor growth. Mechanistically, HER3 activation suppresses the tumor-suppressive microRNA miR-34b-5p, resulting in the upregulation of the histone demethylase PHF8 (KDM7B), which in …

Selective Depletion Of Gut Gram-Negative Bacteria Attenuates Alcohol Binge-Induced Cardiovascular Dysfunction By Lowering Cardiac Anandamide Levels, Sarah E. Cohen, Meagan E. Donovan, Davin J. Gardner, Danielle Sambo, Seray B. Karagoz, Resat Cinar, David Goldman, Jason D. Gardner, Pal Pacher, Janos Paloczi

School of Graduate Studies Faculty Publications

Binge drinking contributes to an increasing number of emergency department visits in the United States. Previous work demonstrated that an alcohol binge impairs cardiac performance and exerts complex hemodynamic effects through the activation of the endocannabinoid-mediated cannabinoid type 1 receptor (CB1R) signaling pathway. Anandamide (AEA), an endogenous CB1R agonist, is synthesized in response to various stressors and tissue injury. However, the role of binge drinking in increasing myocardial AEA levels, which leads to CB1R-dependent cardiodepression, remains unclear. This work studied how endotoxins from intestinal Gram-negative bacteria affect myocardial AEA levels, which further induce CB1R-dependent cardiac dysfunction following acute alcohol intoxication. …

Improving Empathy And Reducing Stigmatization In Pre-Clinical Physician Assistant Students Towards Patient Taking Opioids For Chronic Pain: The Feasibility Of A Perspective-Taking Peer Role-Play Intervention, Barbie Ann Seton Stephen

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: Empathy has been identified as a crucial skill for all healthcare providers who treat patients with chronic pain. It has been directly linked to higher patient satisfaction and improved health outcomes. It has also been linked to reduced burnout, fewer medical errors, and improved job satisfaction among healthcare providers. Despite the many interventions that have been developed to promote empathy, the decline of empathy in healthcare providers and trainees continues to be of great concern, especially in pain management and opioid prescribing, thus affecting the quality of care given to these patients. In physician assistant students, this decline has …

Roux-En-Y Gastric Bypass Is Associated With Increased Intestinal Glucose Uptake In Humans, Florina Corpodean, Maryam Naseri, Michael Kachmar, Julia St Amant, Denis P. Blondin, Owen T. Carmichael, Vance L. Albaugh

School of Medicine Faculty Publications

CONTEXT: In animal models, Roux-en-Y gastric bypass (RYGB) is associated with increased Roux limb intestinal glucose uptake that may contribute to early metabolic benefits, though prospective clinical studies are lacking. OBJECTIVE: The present study aimed to test the hypothesis that Roux limb glucose uptake would increase relative to baseline in a cohort of patients undergoing RYGB. METHODS: RYGB patients underwent preoperative baseline, and 3- and 6-month positron emission tomography/computed tomography postoperative imaging. Maximum and mean standardized uptake values (SUV) were measured from the following predefined regions of interest: cecum, hepatic flexure, splenic flexure, sigmoid colon, duodenal bulb, Roux limb, and …

In Situ-Generated Volumetric Dried Plasma Spots For The Analysis Of Edaravone And Metabolites In Animal Models, Michele Protti, Roberta Di Lecce, Jiri Adamec, Luca G. Regazzoni, Valeria Valsecchi, Claudia Volpi, Roberto Mandrioli, Laura Mercolini

School of Graduate Studies Faculty Publications

In this study, for the first time rat plasma microsampling was carried out by means of in situ-generated volumetric dried plasma spot (vDPS) technology and applied to the determination of the neuroprotective agent edaravone and its sulphate and glucuronide metabolites. Sampling was performed using Telimmune® plasma separation cards (vPSC), which allow the formation of volumetrically accurate dried plasma spots (3 µL) from blood drops deposited on them. After accelerated forced drying and solvent extraction in methanol, drying and redissolution, analytes were baseline separated and quantified through an original HPLC-MS/MS analytical method. Validation assays provided excellent results, with detection limits between …