Medical Specialties Commons^™

Pancreatic Stromal Gremlin 1 Expression During Pancreatic Tumorigenesis, Joy M. Davis, Binglu Cheng, Madeline M. Drake, Qiang Yu, Baibing Yang, Jing Li, Chunhui Liu, Mamoun Younes, Xiurong Zhao, Jennifer M. Bailey, Qiang Shen, Tien C. Ko, Yanna Cao

School of Medicine Faculty Publications

Chronic pancreatitis (CP) is a major risk factor of pancreatic ductal adenocarcinoma (PDAC). How CP promotes pancreatic oncogenesis remains unclear. A characteristic feature of PDAC is its prominent desmoplasia in the tumor microenvironment, composed of activated fibroblasts and macrophages. Macrophages can be characterized as M1 or M2, with tumor-inhibiting or -promoting functions, respectively. We reported that Gremlin 1 (GREM1), a key pro-fibrogenic factor, is upregulated in the stroma of CP. The current study aimed to investigate the expression of GREM1 and correlation between GREM1 and macrophages within the pancreas during chronic inflammation and the development of PDAC. By mRNA in …

A Mathematical Model To Explore The Potential Of Combinations Of Adt And Immunotherapies, Johnna Barnaby

Biology and Medicine Through Mathematics Conference

No abstract provided.

Similac Special Care And Elecare Cause Neonatal Gut Injury In Mice, Karishma Rao, Heather L. Menden, Wei Yu, Inamul Haque, Susana Chavez-Bueno, Alain C. Cuna, Shahid Umar, Venkatesh Sampath

Research Days

No abstract provided.

Clinical Validation And Diagnostic Rate/Outcomes Of A Dual Molecular Diagnostic Assay For Myotonic Dystrophy 1., Maxime Cadieux-Dion, Isabelle Thiffault, Midhat S. Farooqi, Joseph Alaimo

Research Days

No abstract provided.

Culinary Education Programs For Children In Low-Income Households: A Scoping Review, Priscilla P Li, Guisela Mackey, Chishinga Callender, Jayna M Dave, Norma Olvera, Shana Alford, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Child obesity in the United States is at an all-time high, particularly among underserved populations. Home-cooked meals are associated with lower rates of obesity. Helping children develop culinary skills has been associated with improved nutrition. The purpose of this study is to report results from a scoping review of culinary education interventions with children from low-income families. Three databases and hand searches of relevant articles were examined. Retained articles met inclusionary criteria. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, as appropriate. A data extraction template was developed. Data were independently extracted and verified. Only …

Proteolysis-Targeting Chimera (Protac) For Targeted Protein Degradation And Cancer Therapy, Xin Li, Yongcheng Song

Faculty, Staff and Students Publications

Proteolysis-targeting chimera (PROTAC) has been developed to be a useful technology for targeted protein degradation. A bifunctional PROTAC molecule consists of a ligand (mostly small-molecule inhibitor) of the protein of interest (POI) and a covalently linked ligand of an E3 ubiquitin ligase (E3). Upon binding to the POI, the PROTAC can recruit E3 for POI ubiquitination, which is subjected to proteasome-mediated degradation. PROTAC complements nucleic acid-based gene knockdown/out technologies for targeted protein reduction and could mimic pharmacological protein inhibition. To date, PROTACs targeting ~ 50 proteins, many of which are clinically validated drug targets, have been successfully developed with several …

Integrating Geriatric Assessment And Genetic Profiling To Personalize Therapy Selection In Older Adults With Acute Myeloid, Vijaya R. Bhatt

Theses & Dissertations

Integrating geriatric assessment for patient profiling and genetic profiling of leukemic cells represents an innovative approach to personalize therapy selection in older adults with acute myeloid leukemia (AML). We report results of a pre-planned interim analysis of a pragmatic phase II trial that utilized this strategy to personalize therapy. Patients ≥60 years with a new diagnosis of AML underwent geriatric assessment prior to initiation of treatment. Geriatric assessment of physical function, cognitive function and comorbidity burden were used to determine fitness for chemotherapy. Patients with good or intermediate-risk AML received intensive chemotherapy such as anthracycline and cytarabine (7+3) if determined …

The Effects Of Alpha-Tocopherol And Ascorbic Acid On Metastatic Breast Cancer Cells, Scout Treadwell

Honors Theses

Breast cancer is a multifaceted, complex disease that affects hundreds of thousands of patients every year. Although there has a been a decline in the mortality rate of this disease, it is still vital to investigate and discover new possible treatments. One area of research involves the generation of reactive oxygen species (ROS) in cancer cells and the possibility of ROS-induced apoptosis. Antioxidants such as Vitamin C and Vitamin E have been shown to serve as pro-oxidants. Instead of detoxifying the cell from damaging ROS, these compounds can stimulate ROS production, triggering an apoptotic cascade in the cell. In this …

Correlation Of Inflammation In Arthritis With The Myelination In The Brain, Anna Spears

Honors Theses

This study was conducted to investigate whether the influence of arthritis has an effect on the cerebral white matter. The project was performed at the South Oxford Campus, where diffusion tensor imaging (DTI) data was obtained from the Nathan Kline Institute-Rockland Sample (NKI- RS). Image processing was conducted using Functional Magnetic Resonance Imaging of Brain Software Library in which we obtained raw data to formulate Apparent Diffusion Coefficient (ADC), Axial Diffusivity (AD), Radial Diffusivity (RD), and Fractional Anisotropy. A one way Analysis of Covariance (ANCOVA) was performed to determine the significant difference between the history of arthritis on each of …

Computer Based Learning Module: Neuraxial And Peripheral Nerve Blocks, Altan Halici

Doctor of Nursing Practice Projects

Neuraxial and peripheral nerve blocks (PNB) have been present for many years, but recently these pain management techniques are gaining popularity as an alternative to the use of opioids. Neuraxial and PNB reduce the opioid usage during and after the surgery and improve postoperative recovery in terms of pain relief, pain-related sleep disruption, and reduction of side effects, such as nausea and vomiting. Conversely, inadequate pain management after surgery may delay surgical recovery, decreased patient satisfaction, increased length of hospital stay, increased readmissions and healthcare costs (Patacsil, McAuliffe, Feyh, & Sigmon, 2016).

Perioperative nurses are instrumental during the post-operative period …

A Goldenbraid Cloning System For Synthetic Biology In Social Amoebae, Peter Kundert, Alejandro Sarrion-Perdigones, Yezabel Gonzalez, Mariko Katoh-Kurasawa, Shigenori Hirose, Peter Lehmann, Koen J T Venken, Gad Shaulsky

Faculty, Staff and Students Publications

GoldenBraid is a rapid, modular, and robust cloning system used to assemble and combine genetic elements. Dictyostelium amoebae represent an intriguing synthetic biological chassis with tractable applications in development, chemotaxis, bacteria-host interactions, and allorecognition. We present GoldenBraid as a synthetic biological framework for Dictyostelium, including a library of 250 DNA parts and assemblies and a proof-of-concept strain that illustrates cAMP-chemotaxis with four fluorescent reporters coded by one plasmid.

How Can We Stop Cancer?, Joseph R. Current

The Review: A Journal of Undergraduate Student Research

Cancer is a disease that humans have been struggling to combat for centuries. It originates from the accumulation of several mutations over the life of a cell that causes it to evade cell death and multiply rapidly. It can affect any tissue in the body and can spread to other parts of the body through metastasis. Cancer comes in numerous shapes and sizes with different levels of aggression, growth speeds, and health risks. Many treatments for cancer exist today, three of the most popular being surgery, chemotherapy, and radiation therapy, which can be used in combinations with other treatments to …

The Current Neuroscientific Understanding Of Alzheimer's Disease, Rachel A. Brandes

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Alzheimer’s disease is a degenerative neurological illness characterized by the deterioration of brain regions implicated in memory and cognitive function. While researchers have yet to find a cure or effective treatment, they have gained a better understanding of its pathology and development. Through years of neuroscience research, scientists have discovered much of what happens in the brain during Alzheimer’s disease onset and how this causes its symptoms; many hypotheses regarding this aspect of the illness involve temporal lobe atrophy, neurofibrillary tangles, and amyloid plaques. Although Alzheimer’s disease affects millions of people every day, it seems that most are unaware of …

The Evil Twin: The Case Of Heterotopic Pregnancy, Rashmi Jadhav, Vegas Brown, Gabriel Cabrera

West Florida Division GME Research Day 2020

• Heterotopic pregnancy occurs in about 1 in 30,000 naturally conceived pregnancies (5). The risk rises 1-3% for pregnancies occurring through assisted reproductive technologies (ART) (1).
• Isolated ectopic pregnancy affects an average of 1 in every 150 live births (1).
• A known pre-existing intrauterine pregnancy (IUP) can be falsely reassuring and delay the diagnosis of a potentially life-threatening concurrent ectopic pregnancy.
• Presentation is vague and 45% of patients have no symptoms (5).
• Differential Diagnoses: endometritis, incomplete miscarriage, ruptured ovarian cyst, non-GYN cause (ie: appendicitis or UTI).
• Risk Factors: Infertility treatment, in vitro fertilization (IVF), prior ectopic, prior tubal surgery, use of …

Effects Of Alternative Chemotherapeutic Agents On Thyroid Cancer Cell Line Ml-1, Husref Rizvanovic

Graduate Theses/Dissertations

Though differentiated thyroid carcinomas have decent prognosis when detected early, radioactive iodine (RAI) resistant and advanced thyroid cancers are still difficult to treat with existing therapies. Better therapeutic agents are needed. Studies have shown that aggressive thyroid cancers (ML-1) express the extracellular matrix protein, matrix metalloproteinase (MMP-2). MMP-2 has been linked to metastasis and aggressiveness of several cancers and has been shown to play a crucial role in tumor invasion. Chlorotoxin is a selective MMP-2 receptor agonist, and Saporin is a well-known ribosome-inactivating protein used for anti-cancer treatment; however, these two agents have never been studied when conjugated together. I …

Are "Replicants" The Spine Surgeons Of The Future?, Jens R Chapman, Jeffrey C Wang, Karsten Wiechert

Articles, Abstracts, and Reports

No abstract provided.

Hdr Brachytherapy For Skin Cancer Using H.A.M. Applicator, Timothy Richard Thatcher

UNLV Theses, Dissertations, Professional Papers, and Capstones

Skin cancer is the most common type of malignancy affecting both men and women in the United States. A majority of these cases are nonmelanoma skin cancers (NMSC) such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The goal of any skin cancer treatment is to cure the lesion itself while also preserving function and optimizing superficial cosmesis. High dose rate (HDR) brachytherapy provides an alternative to superficial x-ray or electron beam for skin cancer treatment. Utilizing an Iridium 192 source soldered to the end of a wire, surface dose can be administered at predetermined positions with sharper …

The Effects Of Total Body Proton Irradiation On Mouse Myometrium, Lillith Bulawa

Undergraduate Honors Theses

The boundaries of human space exploration continue to expand with new technology and discoveries making it even more important to investigate the effects of space on biological systems. Although humans have explored space in small increments, reproductive studies must be conducted to determine if stable short- or long-term residences for humans can exist in space. This study explored the effects of whole-body proton radiation on uterine smooth muscle known as the myometrium. Two types of mice utilized in this study were C57BL/6 and B6.129S6Cybbtm1Din/J NOX2 knockout mice. C57BL/6 mice are standard laboratory mice that were used to represent the wildtype …

A Protocol Driven Stroke Code's Impact On Door-To-Needle Times, Jesse Osborne

Electronic Theses and Dissertations

Tissue plasminogen activator (tPA) is most effective the faster it is able to be administered to a patient that has been affected by stroke. A Stroke Code is a strategy that acute care facilities implement to reduce the time from diagnosing a stroke to administering tPA. The purpose of this study was to determine if the initiation of a Stroke Code in an acute care hospital reduces the door-to-needle time for patients affected by a stroke. In particular, does a Stroke Code reduce door-to-needle times. The research was conducted using data from April 1, 2014 to December 31, 2014 (pre-Stroke …

Alternative Splicing Of The Slco1b1 Gene: An Exploratory Analysis Of Isoform Diversity In Pediatric Liver., Bianca D. Van Groen, Chengpeng Bi, Roger Gaedigk, Vincent S. Staggs, Dick Tibboel, Saskia N. De Wildt, J Steven Leeder

Manuscripts, Articles, Book Chapters and Other Papers

The hepatic influx transporter OATP1B1 (SLCO1B1) plays an important role in the disposition of endogenous substrates and drugs prescribed to children. Alternative splicing increases the diversity of protein products from > 90% of human genes and may be triggered by developmental signals. As concentrations of several endogenous OATP1B1 substrates change during growth and development, with this exploratory study we investigated age-dependent alternative splicing of SLCO1B1 mRNA in 97 postmortem livers (fetus-adolescents). Twenty-seven splice variants were detected; 10 were confirmed by additional bioinformatic analyses and verified by quantitative polymerase chain reaction, and selected for detailed analysis based on relative abundance, association with …

Estrogen Receptor-Α Expressing Neurons In The Ventrolateral Vmh Regulate Glucose Balance, Yanlin He, Pingwen Xu, Chunmei Wang, Yan Xia, Meng Yu, Yongjie Yang, Kaifan Yu, Xing Cai, Na Qu, Kenji Saito, Julia Wang, Ilirjana Hyseni, Matthew Robertson, Badrajee Piyarathna, Min Gao, Sohaib A Khan, Feng Liu, Rui Chen, Cristian Coarfa, Zhongming Zhao, Qingchun Tong, Zheng Sun, Yong Xu

Children’s Nutrition Research Center Staff Publications

Brain glucose-sensing neurons detect glucose fluctuations and prevent severe hypoglycemia, but mechanisms mediating functions of these glucose-sensing neurons are unclear. Here we report that estrogen receptor-α (ERα)-expressing neurons in the ventrolateral subdivision of the ventromedial hypothalamic nucleus (vlVMH) can sense glucose fluctuations, being glucose-inhibited neurons (GI-ERαvlVMH) or glucose-excited neurons (GE-ERαvlVMH). Hypoglycemia activates GI-ERαvlVMH neurons via the anoctamin 4 channel, and inhibits GE-ERαvlVMH neurons through opening the ATP-sensitive potassium channel. Further, we show that GI-ERαvlVMH neurons preferentially project to the medioposterior arcuate nucleus of the hypothalamus (mpARH) and GE-ERαvlVMH neurons preferentially project to the dorsal Raphe nuclei (DRN). Activation of ERαvlVMH …

Preclinical Studies Of A Novel Idh1 Inhibitor In Acute Myeloid Leukemia (Aml), Vivian Salama

Dissertations and Theses (Open Access)

LY3410738, a novel covalent Isocitrate Dehydrogenase 1 (IDH1) inhibitor in Acute Myeloid Leukemia, it is more effective than Ivosidenib (AG120) and has a potent anti-leukemic effect against IDH1 mutant acute myeloid leukemia in combination with Venetoclax (ABT-199).

Acute myeloid Leukemia (AML) is an aggressive neoplastic blood disorder characterized by proliferation of poorly differentiated cells of myeloid lineage. IDH1 is a cytoplasmic enzyme that catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) in the citric acid cycle. Somatic gain-of-function mutations in IDH1 occur in ~10% of the newly diagnosed AML patients. The neo-enzymatic activity of mutant IDH1 results in accumulation …

Genetic Counselors' Approaches To Direct-To-Consumer Genetic Testing For Hereditary Breast Cancer, Sarah Burke

Dissertations and Theses (Open Access)

Given the increasing availability of health-related direct-to-consumer genetic testing (DTC-GT) and third-party interpretation (TPI) services, it is likely that genetic counselors (GCs) will continue to encounter consumers that require follow-up counseling for their results. The National Comprehensive Cancer Network recommends clinical-grade genetic testing to confirm commercial results; however, the type of testing that GCs select remains uncharacterized. Therefore, we aimed to describe the specific recommendations that cancer GCs make for confirmatory genetic testing in probands who have already obtained DTC-GT results or TPI data that reported a BRCA1/2 pathogenic variant. We recruited 80 GCs specializing in hereditary cancer and administered …

Investigating Medical Examiners' Practices: Genetic Evaluation For Fatal Acute Aortic Dissection, Bradley Power

Dissertations and Theses (Open Access)

Acute thoracic aortic dissection (TAD) is a life-threatening event with a hereditary component. Currently, pathogenic variants in 11 genes associated with aortic aneurysm and dissection predispose to a heritable form of disease thereby conferring an increased risk for TAD. Genetic testing plays a pivotal role not only in diagnosis, but also in risk stratification for relatives and medical management to prevent premature death from dissection. Due to its high fatality rate, medical examiners and coroners (ME/Cs) may be the first to identify TAD cases and initiate genetic testing for the decedent and at-risk relatives. ME/Cs were surveyed using three clinical …

Development Of Fully Balanced Ssfp And Computer Vision Applications For Mri-Assisted Radiosurgery (Mars), Jeremiah Sanders

Dissertations and Theses (Open Access)

Prostate cancer is the second most common cancer in men and the second-leading cause of cancer death in men. Brachytherapy is a highly effective treatment option for prostate cancer, and is the most cost-effective initial treatment among all other therapeutic options for low to intermediate risk patients of prostate cancer. In low-dose-rate (LDR) brachytherapy, verifying the location of the radioactive seeds within the prostate and in relation to critical normal structures after seed implantation is essential to ensuring positive treatment outcomes.

One current gap in knowledge is how to simultaneously image the prostate, surrounding anatomy, and radioactive seeds within the …

Baclofen-Induced Changes In The Resting Brain Modulate Smoking Cue Reactivity: A Double-Blind Placebo-Controlled Functional Magnetic Resonance Imaging Study In Cigarette Smokers, Ariel Ketcherside, Kanchana Jagannathan, Sudipto Dolui, Nathan Hager, Nathaniel Spilka, Chaela Nutor, Hengyi Rao, Teresa Franklin, Reagan Wetherill

Psychology Faculty Publications

Objective: Smoking cue-(SC) elicited craving can lead to relapse in SC-vulnerable individuals. Thus, identifying treatments that target SC-elicited craving is a top research priority. Reduced drug cue neural activity is associated with recovery and is marked by a profile of greater tonic (resting) activation in executive control regions, and increased connectivity between executive and salience regions. Evidence suggests the GABA-B agonist baclofen can reduce drug cue-elicited neural activity, potentially through its actions on the resting brain. Based on the literature, we hypothesize that baclofen’s effects in the resting brain can predict its effects during SC exposure.

Methods: In this longitudinal, …

Impact Of Slco1b1 Genetic Variation On Rosuvastatin Systemic Exposure In Pediatric Hypercholesterolemia., Jonathan B. Wagner, Susan M. Abdel-Rahman, Andrea Gaedigk, R Gaedigk, Geetha Raghuveer, Vincent S. Staggs, Leon Van Haandel, J Steven Leeder

Manuscripts, Articles, Book Chapters and Other Papers

This study investigated the impact of SLCO1B1 genotype on rosuvastatin systemic exposure in hypercholesterolemic children and adolescents. Participants (8-21 years) with at least one allelic variant of SLCO1B1 c.521T>C (521TC, n = 13; 521CC, n = 2) and wild type controls (521TT, n = 13) completed a single oral dose pharmacokinetic study. The variability contributed by SLCO1B1 c.521 sequence variation to rosuvastatin (RVA) systemic exposure among our pediatric cohort was comparable to previous studies in adults. RVA concentration-time curve from 0-24 hours (AUC

Bispecific Human Il2-Ccr4 Immunotoxin Targets Human Cutaneous T-Cell Lymphoma, Haoyu Wang, Zhaohui Wang, Huiping Zhang, Zeng Qi, Ariel C Johnson, David Mathes, Elizabeth A Pomfret, Erin Rubin, Christene A Huang, Zhirui Wang

Faculty, Staff and Student Publications

The majority of clinically diagnosed cutaneous T‐cell lymphomas (CTCL) highly express the cell‐surface markers CC chemokine receptor 4 (CCR4) and/or CD25. Recently, we have developed diphtheria toxin‐based recombinant Ontak®‐like human IL2 fusion toxin (IL2 fusion toxin) and anti‐human CCR4 immunotoxin (CCR4 IT). In this study, we first compared the efficacy of the CCR4 IT vs IL2 fusion toxin for targeting human CD25+CCR4+ CTCL. We demonstrated that CCR4 IT was more effective than IL2 fusion toxin. We further constructed an IL2‐CCR4 bispecific IT. The bispecific IT was significantly more effective than either IL2 fusion toxin or CCR4 IT alone. The bispecific …

Unique Case Of Anca-Negative Pauci-Immune Necrotizing Glomerulonephritis With Diffuse Alveolar Hemorrhage, Potentially Associated With Midostaurin, Jonathan D Pankow, Guillaume Richard-Carpentier, Naval G Daver, William F Glass, Jaya Kala

Faculty, Staff and Student Publications

We present a 61-year-old male with FLT3-mutated acute myeloid leukemia treated with midostaurin who developed acute kidney injury requiring hemodialysis and pulmonary renal syndrome. Antibodies to proteinase-3, myeloperoxidase, and glomerular basement membrane were negative. Renal biopsy confirmed acute pauci-immune focal necrotizing glomerulonephritis (GN) with fibrin crescents indicating rapidly progressing glomerulonephritis. He improved with pulse methylprednisolone, intravenous cyclophosphamide, and plasma exchange with resolution of hemoptysis. This case highlights the importance of prompt renal biopsy to guide early initiation of life-saving therapies. To our knowledge, this is the first reported case of ANCA-negative pauci-immune necrotizing GN likely secondary to midostaurin.

Catabolic Degradation Of Endothelial Vegfa Via Autophagy, Thomas Neill, Carolyn Chen, Simone Buraschi, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Extracellular matrix-evoked angiostasis and autophagy within the tumor microenvironment represent two critical, but unconnected, functions of the small leucine-rich proteoglycan, decorin. Acting as a partial agonist of vascular endothelial growth factor 2 (VEGFR2), soluble decorin signals via the energy sensing protein, AMP-activated protein kinase (AMPK), in the autophagic degradation of intracellular vascular endothelial growth factor A (VEGFA). Here, we discovered that soluble decorin evokes intracellular catabolism of endothelial VEGFA that is mechanistically independent of mTOR, but requires an autophagic regulator, paternally expressed gene 3 (PEG3). We found that administration of autophagic inhibitors such as chloroquine or bafilomycin A1, or depletion …