Digital Commons Network^™

Medial Temporal Lobe Roles In Human Path Integration, Naohide Yamamoto, John W. Philbeck, Adam J. Woods, Daniel A. Gajewski, Joeanna C. Arthur, Samuel J. Potolicchio, Lucien M. Levy, Anthony J. Caputy

Neurological Surgery Faculty Publications

Path integration is a process in which observers derive their location by integrating self-motion signals along their locomotion trajectory. Although the medial temporal lobe (MTL) is thought to take part in path integration, the scope of its role for path integration remains unclear. To address this issue, we administered a variety of tasks involving path integration and other related processes to a group of neurosurgical patients whose MTL was unilaterally resected as therapy for epilepsy. These patients were unimpaired relative to neurologically intact controls in many tasks that required integration of various kinds of sensory self-motion information. However, the same …

Effects Of An Osteoporosis Educational Intervention: Knowledge And Self-Efficacy Of Prevention In Young Adult Collegiate Females, Valerie A. Bollenbacher

Evidence-Based Practice Project Reports

Osteoporosis is a silent and potentially debilitating chronic illness. In 2012, the CDC reported that 4.5 million women over the age of 50 were diagnosed with osteoporosis in the United States. Within the next 20 years, 41 million women worldwide are projected to have osteoporosis. The annual financial burden of osteoporosis is estimated to be 19 billion dollars. The objective of this evidence-based practice project was to answer the clinical question: In young adult collegiate females, how does an osteoporosis educational intervention compared to current education effect osteoporosis knowledge and self-efficacy of osteoporosis prevention over a one-month time period? The …

Novel Roles Of The Protein Tyrosine Phosphatase Shp2 In Non-Small Cell Lung Cancer, Valentina Schneeberger

USF Tampa Graduate Theses and Dissertations

The gene PTPN11 was identified in the early 1990s, and encodes the non-transmembrane protein tyrosine phosphatase SHP2. SHP2 is expressed ubiquitously in cells, and plays an important role in cancer. Unlike most phosphatases, SHP2 positively regulates several signaling pathways including the Ras/MAPK and Src signaling pathways and acts as a proto-oncogene. SHP2 is also a cancer essential gene in certain types of carcinomas, and promotes growth, survival, and epithelial to mesenchymal transformation. Gain of function (GOF) SHP2 mutations are known leukemic oncogenes, and have been identified to a smaller extent in solid tumors as well. Currently, the roles of SHP2 …

Manganese-Containing Prussian Blue Nanoparticles For Imaging Of Pediatric Brain Tumors, Matthieu F. Dumont, Sridevi Yadavilli, Raymond Sze, Javad Nazarian, Rohan Fernandes

Radiology Faculty Publications

Pediatric brain tumors (PBTs) are a leading cause of death in children. For an improved prognosis in patients with PBTs, there is a critical need to develop molecularly-specific imaging agents to monitor disease progression and response to treatment. In this paper, we describe manganese-containing Prussian blue nanoparticles as agents for molecular magnetic resonance imaging (MRI) and fluorescence-based imaging of PBTs. Our core-shell nanoparticles consist of a core lattice structure that incorporates and retains paramagnetic Mn²⁺ ions, and generates MRI contrast (both negative and positive). The biofunctionalized shell is comprised of fluorescent avidin, which serves the dual purpose of enabling …

Pharmacokinetics And Pharmacodynamics Of Antifungals In Children And Their Clinical Implications, Chris Stockmann, Jonathan E. Constance, Jessica K. Roberts, Jared Olson, Elizabeth H. Doby, Krow Ampofo, Justin Stiers, Michael G. Spigarelli, Catherine Mt Sherwin

Pediatrics Faculty Publications

Invasive fungal infections are a significant cause of morbidity and mortality in children. Successful management of these systemic infections requires identification of the causative pathogen, appropriate antifungal selection, and optimisation of its pharmacokinetic and pharmacodynamic properties to maximise its antifungal activity and minimise toxicity and the emergence of resistance. This review highlights salient scientific advancements in paediatric antifungal pharmacotherapies and focuses on pharmacokinetic and pharmacodynamic studies that underpin current clinical decision making. Four classes of drugs are widely used in the treatment of invasive fungal infections in children, including the polyenes, triazoles, pyrimidine analogues and echinocandins. Several lipidic formulations of …

The Role Of Amp-Activated Protein Kinase (Ampk) In Regulating The Early Stages Of Acute Pancreatitis, Mohamed Shitia

Honors Scholar Theses

Acute pancreatitis is an inflammatory disease that is initiated by the activation and retention of digestive zymogens inside pancreatic acinar cells (acini). It is proposed that adenosine monophosphate-activated protein kinase (AMPK) regulates early responses of acute pancreatitis in acini. A recent study shows that induction of experimental pancreatitis in isolated rat acini with supraphysiologic cerulein (orthologue of cholecystokinin) increases intracellular zymogen activation, but decreases AMPK levels. Furthermore, in vitro pharmacologic stimulation of AMPK reduces zymogen activation, having a protective effect. In this study, the effectiveness of two AMPK activators was examined in two separate in vivo pancreatitis models. In the …

Cyclic Nucleotide-Dependent Phosphorylation Regulates Bk-Ca Channel Activity In Human Coronary Artery Smooth Muscle Cells, Raeonda Williams

PCOM Biomedical Studies Student Scholarship

Cardiovascular diseases (CVD) can induce dysfunction in organ systems by attenuating normal blood flow. Gonadal steroids are vasoactive hormones, but their role in contributing to cardiovascular function remains controversial. We have demonstrated that gonadal steroids can relax coronary arteries by opening the large-conductance, calcium- and voltage-activated potassium (BKca) channel in smooth muscle cells by increasing cyclic nucleotide levels; however, the signaling pathways involved remain to be elucidated. The purpose of this study was to identify how phosphorylation (via cAMP- and cGMP-dependent protein kinases) I dephosphorylation (via phosphoprotein phosphatase 2A, PP2A) regulates BKca channel activity in human coronary artery smooth muscle …

Performance Evaluation Of Material Decomposition Using Rapid Kvp-Switching Dual-Energy Ct For Assessing Bone Mineral Density, John M. Wait

Dissertations and Theses (Open Access)

Osteoporosis is diagnosed by assessing the bone mineral density (BMD) of the trabecular bone, and has previously been characterized with dual-energy x-ray absorptiometry (DXA) or single-energy computed tomography (SECT). Dual-energy computed tomography (DECT) is able to create two three-dimensional sets of images representing the densities of two materials in a given basis pair. DECT is theoretically capable of providing a true density measurement of trabecular bone material with the proper material basis pair.

Using the rapid kVp-switching GE HD750 scanner, the concentrations of various solutes were assessed in two-material syringe-phantoms in different experimental conditions with DECT material density images, SECT …

Pharmacologic Suppression Of Jak1/2 By Jak1/2 Inhibitor Azd1480 Potently Inhibits Il-6-Induced Experimental Prostate Cancer Metastases Formation., Lei Gu, Pooja Talati, Paraskevi Vogiatzi, Ana L Romero-Weaver, Junaid Abdulghani, Zhiyong Liao, Benjamin E. Leiby, David T. Hoang, Tuomas Mirtti, Kalle Alanen, Michael Zinda, Dennis Huszar, Marja T. Nevalainen

Department of Medical Oncology Faculty Papers

Metastatic prostate cancer is lethal and lacks effective strategies for prevention or treatment, requiring novel therapeutic approaches. Interleukin-6 (IL-6) is a cytokine that has been linked with prostate cancer pathogenesis by multiple studies. However, the direct functional roles of IL-6 in prostate cancer growth and progression have been unclear. In the present study, we show that IL-6 is produced in distant metastases of clinical prostate cancers. IL-6-activated signaling pathways in prostate cancer cells induced a robust 7-fold increase in metastases formation in nude mice. We further show that IL-6 promoted migratory prostate cancer cell phenotype, including increased prostate cancer cell …

Investigation Of Rice Bran Derived Anti-Cancer Pentapeptide For Mechanistic Potency In Breast Cancer Cell Models, Ruiqi Li

Graduate Theses and Dissertations

Bioactive peptides derived from food sources with anti-proliferative properties against cancer have drawn more attention in recent years. A pentapeptide derived from rice bran has shown anti-proliferative propertiesagainst human breast cancer cells. The objective of this study was to investigate the mechanistic action of the pentapeptide-induced apoptosis in breast cancer cell models (MCF-7 and MDA-MB-231). The growth inhibition activity of the pentapeptide was

evaluated by MTS[3-(4,5-dimethylthiazol-2-yl)-5-(3- arboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assayand trypan blue assay in a dose- and time-dependent manner.

The apoptotic properties of pentapeptide-induced apoptosis on cancerous breast cells were evaluated by morphological changes, DNA fragmentation, and caspases-3/7, -8,and -9 …

Detection Of Vascular Endothelial Growth Factor In Colon Cancer Xenografts Using Bevacizumab Based Near Infrared Fluorophore Conjugate., Bishnuhari Paudyal, Pramila Paudyal, Dilip Shah, Hideyuki Tominaga, Yoshito Tsushima, Keigo Endo

Department of Radiology Faculty Papers

BACKGROUND: The aim of this study was to develop the near infrared fluorescence (NIRF)-based imaging agent for the visualization of vascular endothelial growth factor (VEGF) in colon cancer. AlexaFluor 750 conjugating with bevacizumab, and injected intravenously into nude mice bearing VEGF over-expressing HT29 human colorectal cancer. Optical imaging was performed at 15 min, 24 h and 48 h post injection. Immunofluorescences staining of the tumor sections were performed. HT29 colorectal cancer xenografts were clearly visualized with bevacizumab-AlexaFluor 750.

RESULTS: Ex vivo analysis showed 2.1 ± 0.4%, 37.6 ± 6.3% and 38.5 ± 6.2% injected dose/g accumulated in the tumors at …

Avirulent Strains Of Toxoplasma Gondii Infect Macrophages By Active Invasion From The Phagosome, Yanlin Zhao, Andrew H. Marple, David J. P. Ferguson, David J. Bzik, George S. Yap

Dartmouth Scholarship

Unlike most intracellular pathogens that gain access into host cells through endocytic pathways, Toxoplasma gondii initiates infection at the cell surface by active penetration through a moving junction and subsequent formation of a parasitophorous vacuole. Here, we describe a noncanonical pathway for T. gondii infection of macrophages, in which parasites are initially internalized through phagocytosis, and then actively invade from within a phagosomal compartment to form a parasitophorous vacuole. This phagosome to vacuole invasion (PTVI) pathway may represent an intermediary link between the endocytic and the penetrative routes for host cell entry by intracellular pathogens. The PTVI pathway is preferentially …

Critical Role Of Tnf-Α In Cerebral Aneurysm Formation And Progression To Rupture., Robert M Starke, Nohra Chalouhi, Md, Pascal Jabbour Md, Stavropoula Tjoumakaris, L. Fernando Gonzalez, Robert H. Rosenwasswer Md, Kosuke Wada, Kenji Shimada, David M Hasan, Nigel H Greig, Gary K Owens, Aaron Dumont

Department of Neurosurgery Faculty Papers

BACKGROUND: Alterations in TNF-α expression have been associated with cerebral aneurysms, but a direct role in formation, progression, and rupture has not been established.

METHODS: Cerebral aneurysms were induced through hypertension and a single stereotactic injection of elastase into the basal cistern in mice. To test the role of TNF-α in aneurysm formation, aneurysms were induced in TNF-α knockout mice and mice pretreated with the synthesized TNF-α inhibitor 3,6'dithiothalidomide (DTH). To assess the role of TNF-α in aneurysm progression and rupture, DTH was started 6 days after aneurysm induction. TNF-α expression was assessed through real-time PCR and immunofluorescence staining.

RESULTS: …

Regional-Specific Effects Of Ovarian Hormone Loss On Synaptic Plasticity In Adult Human Apoe Targeted Replacement Mice, Rebecca C. Klein, Shyla Saini, Mary-Louise Risher, Shawn K. Acheson, Rebekah L. Fleming, Hannah G. Sexton, H. Scott Swartzwelder, Scott D. Moore

Biomedical Sciences

The human apolipoprotein ε4 allele (APOE4) has been implicated as one of the strongest genetic risk factors associated with Alzheimer’s disease (AD) and in influencing normal cognitive functioning. Previous studies have demonstrated that mice expressing human apoE4 display deficits in behavioral and neurophysiological outcomes compared to those with apoE3. Ovarian hormones have also been shown to be important in modulating synaptic processes underlying cognitive function, yet little is known about how their effects are influenced by apoE. In the current study, female adult human APOE targeted replacement (TR) mice were utilized to examine the effects of human APOE …

Childhood Achalasia: A Comprehensive Review Of Disease, Diagnosis And Therapeutic Management, Ashanti L. Franklin, Mikael Petrosyan, Timothy D. Kane

Surgery Faculty Publications

Achalasia is an esophageal motility disorder characterized by failure of lower esophageal sphincter (LES) relaxation and is rare in children. The most common symptoms are vomiting, dysphagia, regurgitation, and weight loss. Definitive diagnosis is made with barium swallow study and esophageal manometry. In adults, endoscopic biopsy is recommended to exclude malignancy however; it is not as often indicated in children. Medical management often fails resulting in recurrent symptoms and the ultimate definitive treatment is surgical. Laparoscopic Heller myotomy with or without an anti-reflux procedure is the treatment of choice and has become standard of care for children with achalasia. Peroral …

Processing And Characterization Of Innovative Magnesium Alloys For Biodegradable Orthopaedic Implants, Christopher E. Smith

Dissertations

There is a need for innovation in medical implant devices through novel biomaterials that will improve the quality of life. The first step in the creation of a foundation of knowledge and technology to improve these implant devices is through the creation of new alloys with the capabilities of biodegradation and bioabsorption without a toxic effect that will pass through FDA regulatory procedures. In this study, unique heat treatment processing techniques coupled with innovation in elemental alloying produced distinctive magnesium (Mg) based alloy systems. The MgZnCa system was used as the underpinning system where four groups of novel alloys were …

Evidence For Aberrant Astrocyte Hemichannel Activity In Juvenile Neuronal Ceroid Lipofuscinosis (Jncl)., Maria Burkovetskaya, Nikolay Karpuk, Juan Xiong, Megan Bosch, Michael D. Boska, Hideyuki Takeuchi, Akio Suzumura, Tammy Kielian

Journal Articles: Pathology and Microbiology

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) is a lysosomal storage disease caused by an autosomal recessive mutation in CLN3 that leads to vision loss, progressive cognitive and motor decline, and premature death. Morphological evidence of astrocyte activation occurs early in the disease process and coincides with regions where neuronal loss eventually ensues. However, the consequences of CLN3 mutation on astrocyte function remain relatively ill-defined. Astrocytes play a critical role in CNS homeostasis, in part, by their ability to regulate the extracellular milieu via the formation of extensive syncytial networks coupled by gap junction (GJ) channels. In contrast, unopposed hemichannels (HCs) have …

Pharmaceuticals And Personal Care Products: Emerging Contaminants In Aquatic Ecosystems, Jenny E. Zenobio

Open Access Theses

In recent years, the presence of pharmaceuticals and personal care products (PPCPs) in aquatic systems has led to research on their fate and effects. PPCPs have been found in mixture in wastewater effluents, surface, ground, and drinking water at low concentrations from areas of intense urbanization. Although adverse effects to human health from the current environmental concentrations are unlikely, the impacts to ecological receptors are not clear. We performed field and laboratory studies to quantify and evaluate effects of PPCPs on fish. First, a field study was conducted at the Baca National Wildlife Refuge, Colorado (2010-2012) because a portion of …

Oncolog, Volume 59, Number 04, April 2014, Zach Bohannan, Joe Munch, J. Delsigne

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• New fat Grafting Technique Improves Aesthetic Outcomes Following Head and Neck Reconstructive Surgery: A new gat grafting technique is enabling reconstructive surgeons to maximize aesthetic outcomes following major reconstruction for head and neck cancer treatment-related defects
• INBRIEF: Invasive Bladder Cancer Subtypes Resemble Breast Cancer Subtypes
• New Kinase Inhibitors Hold Promise for Chronic Lymphocytic Leukemia, Other B-Cell Malignancies: New targeted therapies against chronic lymphocytic leukemia (CLL) are eliciting overall response rates similar to those achieved using standard chemoimmunotherapy but with fewer toxic effects
• HOUSE CALL: Animal-Assisted Therapy- Interacting with pets helps recovery

Firesetting Behavior And Associated Comorbid Psychiatric Disorders, Stephanie Stockburger, Hatim A. Omar

Pediatrics Faculty Publications

Firesetting behavior results in serious damage to lives and property every year. Firesetting has been linked to a number of comorbid psychiatric disorders including depression, substance abuse, conduct disorder, antisocial personality disorder, obsessive compulsive disorder, psychotic disorder, schizoid personality disorder, and schizophrenia. Psychiatric disorders differ by gender. In addition, juvenile firesetters have history of a separate set of psychiatric comorbidities. The strong correlation between psychiatric comorbidities and firesetting behavior illustrates the need for fire service and mental health collaboration.

Bisphenol A Increases Atherosclerosis In Pregnane X Receptor-Humanized Apoe Deficient Mice, Yipeng Sui, Se-Hyung Park, Robert N. Helsley, Manjula Sunkara, Frank J. Gonzalez, Andrew J. Morris, Changcheng Zhou

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Bisphenol A (BPA) is a base chemical used extensively in many consumer products. BPA has recently been associated with increased risk of cardiovascular disease (CVD) in multiple large-scale human population studies, but the underlying mechanisms remain elusive. We previously reported that BPA activates the pregnane X receptor (PXR), which acts as a xenobiotic sensor to regulate xenobiotic metabolism and has pro-atherogenic effects in animal models upon activation. Interestingly, BPA is a potent agonist of human PXR but does not activate mouse or rat PXR signaling, which confounds the use of rodent models to evaluate mechanisms of BPA-mediated CVD risk. …

Tumor Radiation Therapy Creates Therapeutic Vaccine Responses To The Colorectal Cancer Antigen Gucy2c., Matthew Witek, Erik S Blomain, Michael Sullivan Magee, Bo Xiang, Scott A Waldman, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

PURPOSE: Radiation therapy (RT) is thought to produce clinical responses in cancer patients, not only through direct toxicity to cancer cells and supporting tumor stroma cells, but also through activation of immunologic effectors. More recently, RT has potentiated the local and systemic effects of cancer immunotherapy (IT). However, combination regimens that maximize immunologic and clinical efficacy remain undefined.

METHODS AND MATERIALS: We evaluated the impact of local RT on adenoviral-mediated vaccination against the colorectal cancer antigen GUCY2C (Ad5-GUCY2C) in a murine subcutaneous tumor model using mouse CT26 colon cancer cells (CT26-GUCY2C). Immune responses were assessed by ELISpot, and clinical responses …

Isoflavones And Alzheimer’S Disease: The Effects Of Soy In Diet, Sara Habib, Asad Ali Khan Afridi, Mohammad Wasay, Romaina Iqbal

Pakistan Journal of Neurological Sciences (PJNS)

Pathologically, Alzheimer’s disease is a result of aggregation of amyloid peptides and protein tau in the brain forming neurofibrillary tangles which are highly toxic to neuronal circuits in the brain. Recent evidences report that apart from aging, estrogen deficiency is one of the risk factors predisposing to the development of Alzheimer’s disease. Isoflavones, also known as phytoestrogens, are metabolized by the body forming compounds that are known to interfere with neurotoxic pathways and through their anti-fibrillization effects they play a role in reducing apoptosis of neurons and glial cells and promote axonal regeneration. Experimental studies on transgenic models with Alzheimer’s …

The 1,000th Vad, The Great Rivalry, And The Grand Experiment Of The Texas Medical Center, Todd K Rosengart

The Texas Heart Institute Journal

No abstract provided.

The Odyssey Of Tavr From Concept To Clinical Reality, Alain G Cribier

The Texas Heart Institute Journal

No abstract provided.

Ultrasound-Enhanced Ocular Delivery Of Dexamethasone Sodium Phosphate: An In Vivo Study, Marjan Nabili, Aditi Shenoy, Shawn Chawla, Sankaranarayana P. Mahesh, Craig Geist, Vesna Zderic

Ophthalmology Faculty Publications

Background

The eye's unique anatomy and its physiological and anatomical barriers can limit effective drug delivery into the eye.

Methods

An in vivo study was designed to determine the effectiveness and safety of ultrasound application in enhancing drug delivery in a rabbit model. Permeability of a steroid ophthalmic drug, dexamethasone sodium phosphate, was investigated in ultrasound- and sham-treated cases. For this study, an eye cup filled with dexamethasone sodium phosphate was placed on the cornea. Ultrasound was applied at intensity of 0.8 W/cm² and frequency of 400 or 600 kHz for 5 min. The drug concentration in aqueous humor …

A Novel Multivalent, Single-Domain Antibody Targeting Tcda And Tcdb Prevents Fulminant Clostridium Difficile Infection In Mice, Zhiyong Yang, Diane Schmidt, Weilong Liu, Shan Li, Lianfa Shi, Jinliang Sheng, Kevin Chen, Hua Yu, Jacqueline M. Tremblay, Xinhua Chen, Kurt H. Piepenbrink, Eric J. Sundberg, Ciaran P. Kelly, Guang Bai, Charles B. Shoemaker, Hanping Feng

Food for Health: Publications

The incidence of Clostridium difficile infection (CDI) and associated mortality have increased rapidly worldwide in recent years. Therefore, it is critical to develop new therapies for CDI. In this study, we generated a novel, potently neutralizing, tetravalent, and bispecific antibody composed of 2 heavy-chain-only V_H (V_HH) binding domains against both TcdA and TcdB (designated “ABA”) that reverses fulminant CDI in mice infected with an epidemic 027 strain after a single injection of the antibody. We demonstrated that ABA bound to both toxins simultaneously and displayed a significantly enhanced neutralizing activity both in vitro and in vivo. Additionally, …

A Novel Curcumin Analog (H-4073) Enhances The Therapeutic Efficacy Of Cisplatin Treatment In Head And Neck Cancer, Bhavna Kumar, Arti Yadav, Kalman Hideg, Periannan Kuppusamy

Dartmouth Scholarship

Chemotherapy constitutes the standard modality of treatment for localized head and neck squamous cell carcinomas (HNSCC). However, many patients fail to respond and relapse after this treatments due to the acquisition of chemo- resistance. Therefore, there is an urgent need to develop novel drugs that could reverse the resistant phenotype. Curcumin, the constituent of the spice turmeric has been shown to have anti-inflammatory, anti-oxidant and anti-proliferative properties in several tumor types. However, use of curcumin has been limited due to its poor bio-absorption. Recently, a novel class of curcumin analogs, based on diarylidenylpiperidones (DAP), has been developed by incorporating a …

2014 Massachusetts Family Impact Seminar: A Lot On Our Plate; Chronic Health Threats In Massachusetts, Ira S. Ockene M.D., Christina D. Economos Ph.D, Barbara Goldoftas Ph.D, Denise A. Hines Ph.D., Caitlin Alcorn, Jacqueline A. Daigneault, Jordan R. Daley, Maura A. Flanagan, Carsten-Hendrik Rasche, Heather Rios, Julia Tran, Liam Kelly Fleming

Mosakowski Institute for Public Enterprise

A Lot on Our Plate: Chronic Health Threats in Massachusetts is the fifth Massachusetts Family Impact Seminar, and is designed to emphasize a family perspective in policymaking on issues related to childhood obesity, cardiovascular disease, and type 2 diabetes. In general, Family Impact Seminars analyze the consequences an issue, policy, or program may have for families.

Physiology And Advancements In Wound Healing, Adam Baker, Md

Department of Otolaryngology - Head and Neck Surgery Presentations and Grand Rounds

Outline of presentation:

Fundamentals

Advances

• -Growth Factors
• -Platelet Rich Plasma
• -Engineered skin
• -Hyperbaric Oxygen Therapy

Research