Therapeutics Commons^™

Ido1 And Inflammatory Neovascularization: Bringing New Blood To Tumor-Promoting Inflammation, Alexander J. Muller, Arpita Mondal, Souvik Dey, George C Prendergast

Kimmel Cancer Center Faculty Papers

In parallel with the genetic and epigenetic changes that accumulate in tumor cells, chronic tumor-promoting inflammation establishes a local microenvironment that fosters the development of malignancy. While knowledge of the specific factors that distinguish tumor-promoting from non-tumor-promoting inflammation remains inchoate, nevertheless, as highlighted in this series on the 'Hallmarks of Cancer', it is clear that tumor-promoting inflammation is essential to neoplasia and metastatic progression making identification of specific factors critical. Studies of immunometabolism and inflamometabolism have revealed a role for the tryptophan catabolizing enzyme IDO1 as a core element in tumor-promoting inflammation. At one level, IDO1 expression promotes immune tolerance …

The Effects Of Exosomal Derived Tsg-6 On Microglia Activation, Jonathan A. Martinez, Rajashekhar Gangaraju Md

Longitudinal Scholar's Project

Following a traumatic brain injury, microglia become overactive for long periods and display pathologic behavior. We have shown that concentrated conditioned media from adipose tissue-derived mesenchymal stem cells (MSC-CCM) can suppress microglial activation. In this pilot study, we evaluated the efficacy of exosomes containing TNF-stimulated gene 6 (TSG6) derived from MSC-CCM on decreasing microglial activation in vitro via phagocytic activity and pro-inflammatory microglial gene expression.

Chewed Versus Swallowed Ticagrelor In P2y12 Inhibitor-Naïve Patients Undergoing Percutaneous Coronary Intervention, Thomas F. Wilson, Muddasir Ashraf, M. Fuad Jan, Tonga Nfor, Louie Kostopoulos, Joaquin Solis, Jayant Khitha, Ahmad Khraisat, Anthony C. Defranco, Tanvir Bajwa, Suhail Q. Allaqaband

Journal of Patient-Centered Research and Reviews

Purpose: Dual antiplatelet therapy is standard for patients undergoing percutaneous coronary intervention (PCI) with stents. Traditionally, patients swallow the loading dose of a P2Y12 inhibitor before or during PCI. Time to achieve adequate platelet inhibition after swallowing the loading dose varies significantly. Chewed tablets may allow more rapid inhibition of platelet aggregation. However, data for this strategy in patients with stable ischemic heart disease or non-ST-elevation acute coronary syndrome (NSTE-ACS) are less robust.

Methods: In this single-center prospective trial, 112 P2Y12-naïve patients with stable ischemic heart disease or NSTE-ACS on aspirin therapy and who received ticagrelor after coronary angiography but …

Poor Seizure Control Among Children Attending A Tertiary 8 Hospital In South Western Uganda – A Retrospective Study [Response To Letter], Martha Sajatovic

Faculty Scholarship

No abstract provided.

The Effects Of Specialized Pro-Resolving Mediator Lipoxin A4 On Pseudomonas Aeruginosa Biofilms And Interactions With Monocytes, Julianne M. Thornton

Graduate School of Biomedical Sciences Theses and Dissertations

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen known as a major cause of hospital-acquired secondary infections, commonly causing chronic respiratory infections in immunocompromised individuals, especially those with cystic fibrosis, and often found in wound infections. P. aeruginosa uses the quorum sensing pathway to readily form protective biofilms, which reduce the efficacy of antibiotics and access by host immune cells to eradicate the pathogen. Specialized pro-resolving mediators (SPMs) are lipids endogenously produced by the host immune response to infection to aid in infection resolution. One SPM, Lipoxin A4 (LxA4), has been shown to be a robust quorum sensing inhibitor.

The …

Effects Of Coordinated Reset Deep Brain Stimulation Of Subthalamic Nucleus On Parkinsonian Gait In The Non-Human Primate Model, Kanon Nakajima

Neuroscience Honors Projects

Parkinson’s Disease (PD) is a neurodegenerative disorder that affects over 10 million people worldwide. Deep Brain Stimulation (DBS) has been a successful treatment for advanced PD, however, can be accompanied with current spread related side effects. Coordinated Reset (CR) DBS is a novel therapeutic approach that could reduce the risk of side-effects by using lower current. Previous research has shown therapeutic effects of CR DBS on PD motor symptoms including akinesia, bradykinesia, rigidity, and tremor that sustained after stimulation cessation (i.e., carryover effect), however its effect on gait dysfunction is unknown even though it can be one of the most …

Accuracy Of Therapeutic Drug Monitoring In Vancomycin And The Pharmacist Role: A Retrospective Case-Series, Kateryna Parkhomenko

Senior Theses

Vancomycin is a mainstay of therapy for treating virulent and resistant infections, especially methicillin-resistant Staphylococcus aureus (MRSA). However, vancomycin requires therapeutic drug monitoring (TDM) for optimal dosing and treatment. This requires pharmacists to calculate a dosing regimen that correlates to appropriate goal vancomycin concentrations in the blood. Dosing vancomycin can be difficult, as it varies on a patient’s weight, renal function, age, etc. Doses may have to be adjusted in response to out-of-range concentrations, which requires further pharmacy calculations. Inaccurate dosing poses a risk to patient safety and places a resource and time burden on pharmacists. If vancomycin dosing methods …

A Design, Development, And Evaluation Of Bio-Patch For Myocardial Tissue Repair, Yaya Zhang

Theses and Dissertations (ETD)

Introduction. Ischemic heart disease (IHD) is a major concern of human health issue. The structural repair and functional recovery of injured hearts is a major challenge in the clinical setting. Preclinical studies over last 10 years have demonstrated the potential of using stem cells to treat IHD, but the efficacy of this therapy is jeopardized by uncontrollable migration and low survival of the injected stem cells. An approach based on tissue engineering enabling target-specific stem cell delivery such as cardiac patches has emerged as an alternative solution for stem cell therapy for IHD. It employs scaffold materials to engulf various …

Investigation Of Clinically Relevant Fluconazole Resistance Mechanisms In The Fungal Pathogen Candida Parapsilosis, Laura Anne Doorley

Theses and Dissertations (ETD)

Invasive candidiasis is a severe fungal infection associated with significant morbidity and mortality, particularly among the critically ill and immunocompromised. Candida parapsilosis is the most common non-albicans species causing invasive Candida infections in pediatric and neonatal populations worldwide and is particularly common in the countries of South America, Western Asia, Mediterranean Europe, and Southern Africa. For many of these countries, fluconazole and other triazoles are the first line antifungal agents used for effective treatment of invasive Candida infection. Until recently, rates of fluconazole resistance among C. parapsilosis isolates were relatively low, therefore the determination of clinically relevant resistance mechanisms in …

Poor Seizure Control Among Children Attending A Tertiary Hospital In South Western Uganda – A Retrospective Study, Martha Sajatovic

Faculty Scholarship

Background: Seizure control among children with epilepsy (CWE) receiving anti-seizure medications (ASMs) remains a challenge in low-resource settings. Uncontrolled seizures are significantly associated with increased morbidity and mortality among CWE. This negatively impacts their quality of life and increases stigma. Aim: This study determined seizure control status and described the factors associated among CWE receiving ASMs at Mbarara Regional Referral Hospital (MRRH). Methods: In a retrospective chart review study, socio-demographic and clinical data were obtained from 112 medical records. CWE receiving ASMs for at least six months and regularly attending the clinic were included in the study. Physical or telephone …

Sulopenem For The Treatment Of Complicated And Uncomplicated Bacterial Urinary Tract Infection (Uti), Aiyi Chen, Thanh-Liem Vu, Daniel J. Yang, Landon Olsen

Annual Research Symposium

No abstract provided.

Chimeric Antigen Receptor T-Cell Therapy And Hematopoiesis, Bryanna Reinhardt, Patrick Lee, Joshua P. Sasine

School of Medicine Faculty Publications

Chimeric Antigen Receptor (CAR) T-cell therapy is a promising treatment option for patients suffering from B-cell- and plasma cell-derived hematologic malignancies and is being adapted for the treatment of solid cancers. However, CAR T is associated with frequently severe toxicities such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), macrophage activation syndrome (MAS), and prolonged cytopenias—a reduction in the number of mature blood cells of one or more lineage. Although we understand some drivers of these toxicities, their mechanisms remain under investigation. Since the CAR T regimen is a complex, multi-step process with frequent adverse events, ways …

Mitochondria As Causes Of And Therapeutic Targets In Chronic Post-Sepsis Skeletal Muscle Weakness, Meagan Scott Kingren

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis, or the organ damage that ensues after the body fails to properly contain a local infection, is the leading cause of in-patient hospitalization in the United States. Advances in critical care medicine over the last 20 years have enabled most sepsis patients to survive the life-threatening dysregulated immune response. However, a majority of survivors report chronic weakness and fatigue years after sepsis, and the cause of this weakness remains largely unknown. This dissertation work focused first on elucidating the major causes of post-sepsis muscle weakness (Aim 1). This aim involved a time-course study to determine when muscle weakness was …

Physiologically-Based Pharmacokinetic (Pbpk) Modeling For The Preclinical Development Of Spectinamide Antibiotics, Keyur R. Parmar

Theses and Dissertations (ETD)

Despite being an ancient disease caused by Mycobacterium tuberculosis (Mtb) and after decades of research, tuberculosis (TB) still affects millions of people every year worldwide. In 2018, the World Health Organization (WHO) reported that 10 million people developed tuberculosis and 1.5 million died of the disease. With the increase in the multidrug-resistant (MDR) and extensively drug-resistant (XDR) cases, the treatment for TB with the standard first and second-line therapy is becoming increasingly difficult. Therefore, there is an urgent need to find new anti-TB drugs as combination partners of existing and experimental classes of antimicrobial agents to shorten and simplify the …

Deciphering The Salivary Microbiome In Crohn’S Disease Patients With Different Factors Contributing To Dysbiosis, Hala Elzayat

Theses

Crohn’s Disease (CD) is a chronic Inflammatory Bowel Disease (IBD), common in the UAE. Microbiota is necessary to maintain a balanced gut environment which is essential for good health. Dysbiosis can predispose to many diseases including CD. The oral cavity has the second largest and most diverse microbiota after the gut harboring over 700 species of bacteria. This study aims to investigate the alterations in the salivary microbiome in patients with CD compared to Healthy controls (HC). It also aims to compare CD patients for salivary microbiome complexity and diversity according to different factors that can contribute to dysbiosis, including …

Transmission Competence Of B. Burgdorferi Infected Ixodes Ticks And Development Of An Ospc-Based Lyme Disease Vaccine, Samanta Kamalika

Theses and Dissertations (ETD)

Introduction. Lyme disease, otherwise called Lyme borreliosis, is a vector-borne infectious disease caused by the spirochete Borrelia burgdorferi (Bb). Studying the increase in overall Lyme disease incidence requires understanding the role of the vector Ixodes scapularis (I. scapularis) as the agent that carries the spirochete which is important to limit the occurrence of Lyme disease. Once we understand the vector-pathogen response, it also becomes important to determine the remedies for Lyme disease. Lyme disease can be treated with antibiotics if detected early, but the major obstacle lies in the early detection process. Therefore, it is important to investigate alternative preventive …

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

UROP Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill

SURE Journal: Science Undergraduate Research Experience Journal

Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities …

A Systematic Review And Meta-Analysis: Assessment Of Hospital Walking Programs Among Older Patients, Christine Loyd, Yue Zhang, Tara Weisberg, James Boyett, Elizabeth R. Huckaby, Jeri Grundhoefer, Steve Otero, Lisa Roberts, Samantha Giordano-Mooga, Carmen Capo-Lugo, Catherine H. Smith, Richard E. Kennedy, Barbara J. King, Cynthia J. Brown

School of Medicine Faculty Publications

Aim: The aim of this study is to assess effect of hospital walking programs on outcomes for older inpatients and to characterize hospital walking dose reported across studies. Design: A systematic review and meta-analysis examining impact of hospital walking and/or reported walking dose among medical-surgical inpatients. For inclusion, studies were observational or experimental, published in English, enrolled inpatients aged ≥ 65 yrs hospitalized for medical or surgical reasons. Methods: Searches of PubMed, CINAHL, Embase, Scopus, NICHSR, OneSearch, ClinicalTrials.gov, and PsycINFO were completed in December 2020. Two reviewers screened sources, extracted data, and performed quality bias appraisal. Results: Hospital walking dose …

Targeting Myeloid Protein Kinase C Signaling To Overcome Immune Suppression And Improve Immunotherapy In Cancer, Mehdi Chaib

Theses and Dissertations (ETD)

Checkpoint immunotherapy unleashes T cell antitumor potential which has revolutionized cancer treatment showing unprecedented long-term responses. However, most patients do not respond to immunotherapy which often correlates with a dysfunctional or immunosuppressive myeloid compartment. Immunosuppressive myeloid cells comprise Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) and can suppress T cells via production of immunosuppressive factors. Conversely, efficient cytotoxic T cell priming is dependent on the ability of antigen-presenting cells (APCs), mainly conventional dendritic cells (cDCs) and macrophages, to present or cross-present tumor antigens to T cells. Thus, targeting immunosuppressive myeloid cells while simultaneously enhancing APCs represents a promising strategy …

Interaction Of Fluorescent Probes With Sirtuin Proteins, James Fusco, Brian P Weiser

Rowan-Virtua Research Day

Sirtuins are a class of proteins belonging to the Sir2 (Silencing information regulator 2) family of NAD+ dependent protein lysine deacylases. Different Isoforms (SIRT1-SIRT7) differ in their specific deacylase activity and cellular location. They have roles in DNA repair, glucose metabolism, and cellular proliferation which make them highly desirable targets for carcinoma therapeutics. We previously used 1-aminoanthracene’s (AMA) fluorescent properties when bound with SIRT2 (Kd of 37 μM) to develop a high-throughput screen to identify novel ligands that inhibit SIRT2’s enzymatic activities. We hope to reveal other potential probes for future high-throughput screening with all the sirtuin isotopes. 1-AMA’s fluorescence …

Cases From A Community Hospital… Jchimp Series #1: 55-Year-Old Male With Acute Pe Who Developed Persistent Epistaxis., Jerrica N. Mueller, Bobby Mathew, Douglas D. Reh, Joseph Fuscaldo

Journal of Community Hospital Internal Medicine Perspectives

This is the first in a new series of case reports that will present real scenarios from our community hospital. The cases are chosen to highlight clinical dilemmas and offer review and perspective on what is currently known about the topic. We present the case of a 55-year-old Caucasian male who presented to the emergency department of our community hospital for worsening dyspnea. Evaluation in the Emergency department revealed a diagnosis of extensive pulmonary emboli in the pulmonary vasculature. The patient was admitted to the ICU. A clinical decision was made to initiate treatment with low-dose tissue plasminogen activator (tpa) …

Targeting Metabolic Adaptations To Anti-Angiogenic Therapy In Ovarian Cancer, Deanna M. Glassman, Deanna Glassman

Dissertations and Theses (Open Access)

ABSTRACT

Background: Ovarian cancer is the most lethal gynecologic malignancy. Despite modest clinical improvements with anti-VEGF antibody (AVA) therapy, adaptive resistance is nearly ubiquitous and additional therapeutic options are limited. A dependence on glutamine metabolism, via the enzyme glutaminase (GLS), is a known mechanism of adaptive resistance.

Purpose: To assess the efficacy of a glutaminase inhibitor as a means of exploiting the metabolic vulnerability of glutamine dependence that develops as a result of adaptive resistance to AVA therapy.

Experimental Design: We used a glutaminase inhibitor (GLSi) synthesized at MD Anderson Cancer Center for all in vitro and in vivo experiments. …

Early Detection Of Atypical Motor And Neurobehavior Of Infants At Risk Secondary To Opioid Exposure: A Prospective Study, Kara Boynewicz

Electronic Theses and Dissertations

Prenatal opioid exposure has been studied in relation to infants' medical outcomes. However, large gaps exist in the literature supporting early identification of atypical neurobehavior and motor development of infants with prenatal opioid exposure. The purpose of the study was to investigate whether prenatal opioid exposure has a negative influence on a newborn infant’s neurobehavior and motor development to aid in the early identification of potential delays. Using a prospective quasi experimental design, infants motor development using the Test of Infant Motor Performance (TIMP) and neurobehavior using the NICU Neonatal Network Scale (NNNS) was assessed on 58 infants in a …

Synthesis, Structural Characterization, And In Vitro Biological Assessment Of Trans- Platinum (Ii) Thionate Complexes As Potent Anticancer Agents, Mia Alshami

Chemistry & Biochemistry Undergraduate Honors Theses

The content of this thesis has been originally reported in our published paper, “trans-Platinum (II) Thionate Complexes: Synthesis, Structural Characterization, and in vitro Biological Assessment as Potent Anticancer Agents” ChemPlusChem 2019 84, 1525-1535, DOI: 10.1002/cplu.201900394, in which I served as coauthor. Cancer caused 9.6 million deaths in 2018 worldwide, with 18.1 million new diagnoses during that same year.The most widely used metal in anticancer drugs is platinum (Pt), and these drugs are used to treat almost 50% of cancer patients. To optimize drug effectiveness, trans-configured Pt(II) complexes have been introduced as a strategy to potentially overcome the …

Gene Therapy And Biomedical Applications, Sarah Dundore, Leena Pattarkine

Harrisburg University Research Symposium: Highlighting Research, Innovation, & Creativity

Gene therapy has many uses today through the new treatment options and its potential to treat uncurable diseases. (Class Project)

Psycho-Emotional Education For Occupational Therapists Supporting Individuals Assuming The Role Of Family-Caregiver For People With A Traumatic Brain Injury (Tbi), Laura Dawn Lippman, Caitlyn E. Baird, Natalie L. Billharz

2022 Celebration of Scholarly Works

The purpose of this research was to identify the psycho-emotional needs of family-caregivers of individuals who sustained a traumatic brain injury (TBI), and measure if there was a change in knowledge among occupational therapists, and occupational therapy students following a two-hour seminar covering topics identified in the literature. The topics covered in the seminar included the concept of ambiguous loss, the importance of validating emotions, the caregiver grieving process, and the importance of providing caregiver resources. To measure the change in knowledge, researchers utilized primarily a quantitative research design using pre- and post-test questionnaires with Likert- scale questions. The questionnaire …

Succinic Semialdehyde Dehydrogenase Deficiency (Ssadhd): Qualitative Needs Assessment For Patients With A Rare Neurological Disorder, Cassandra Bovee, Kayla Woodring

Annual Research Symposium

No abstract provided.

Current And Novel Neuroregenerative Therapies, Arrin Brooks

Theses, Dissertations and Capstones

Underlying the physical and cognitive deficits consequent of many neuropathologies is one common factor, the loss of neurons. While neurodegenerative diseases, stroke, and traumatic brain injury arise from a variety of etiologies, they all ultimately result in injury and/or death of neuronal cells and concomitant functional deficits. In the present work we primarily focus on current and potential treatments for localized lesions, particularly those in the striatum of Parkinson’s disease (PD) or the cortex as in stroke. First, we discuss a new surgical technique for deep brain stimulator (DBS) placement, as DBS is a mainstay treatment for movement disorders including …

Aneurysmal Subarachnoid Hemorrhage And Acute Subdural Hematoma, Neurosurgical And Endovascular Rescue. Case Report., José Omar Santellan Resident, José Ramón Aguilar Dr., Abraham Ibarra Dr., Ulises García Dr.

Archives of Neurosurgery

Introduction: Acute subdural hemorrhage (aSDH) in association with aneurismal subarachnoid hemorrhage (SAH) is a severe disease with an incidence of 0.5% to 7.9% of all SAH. Due to the rarity of aneurysmal aSDH, it remains difficult to define a comprehensive management protocol. In this case review, following the CARE guidelines, we show the hybrid management of this pathology to know the importance of using different types of neurosurgical treatments in case of two severe diseases in critical patients.

We present two patients who developed sudden onset cephalea and neurological impairment secondary to aneurysmal subarachnoid hemorrhage associated with acute subdural hematoma. …