Medical Pharmacology Commons^™

Ctpathway: A Crosstalk-Based Pathway Enrichment Analysis Method For Cancer Research, Haizhou Liu, Mengqin Yuan, Ramkrishna Mitra, Xu Zhou, Min Long, Wanyue Lei, Shunheng Zhou, Yu-E Huang, Fei Hou, Christine M. Eischen, Wei Jiang

Department of Cancer Biology Faculty Papers

Background: Pathway enrichment analysis (PEA) is a common method for exploring functions of hundreds of genes and identifying disease-risk pathways. Moreover, different pathways exert their functions through crosstalk. However, existing PEA methods do not sufficiently integrate essential pathway features, including pathway crosstalk, molecular interactions, and network topologies, resulting in many risk pathways that remain uninvestigated.

Methods: To overcome these limitations, we develop a new crosstalk-based PEA method, CTpathway, based on a global pathway crosstalk map (GPCM) with >440,000 edges by combing pathways from eight resources, transcription factor-gene regulations, and large-scale protein-protein interactions. Integrating gene differential expression and crosstalk effects in …

Lysine Methyltransferase Nsd1 And Cancers: Any Role In Melanoma?, Imène Krossa, Thomas Strub, Andrew E Aplin, Robert Ballotti, Corine Bertolotto

Department of Cancer Biology Faculty Papers

Epigenetic regulations, that comprise histone modifications and DNA methylation, are essential to processes as diverse as development and cancer. Among the histone post-translational modifications, lysine methylation represents one of the most important dynamic marks. Here, we focused on methyltransferases of the nuclear binding SET domain 1 (NSD) family, that catalyze the mono- and di-methylation of histone H3 lysine 36. We review the loss of function mutations of NSD1 in humans that are the main cause of SOTOS syndrome, a disease associated with an increased risk of developing cancer. We then report the role of NSD1 in triggering tumor suppressive or …

Diverging Effects Of Adolescent Ethanol Exposure On Tripartite Synaptic Development Across Prefrontal Cortex Subregions, Christopher Douglas Walker, Hannah Gray Sexton, Jentre Hyde, Brittani Greene, Mary-Louise Risher

Biomedical Sciences

Adolescence is a developmental period that encompasses, but is not limited to, puberty and continues into early adulthood. During this period, maturation and refinement are observed across brain regions such as the prefrontal cortex (PFC), which is critical for cognitive function. Adolescence is also a time when excessive alcohol consumption in the form of binge drinking peaks, increasing the risk of long-term cognitive deficits and the risk of developing an alcohol use disorder later in life. Animal models have revealed that adolescent ethanol (EtOH) exposure results in protracted disruption of neuronal function and performance on PFC-dependent tasks that require higher-order …

Novel Drugs Approved In 2021-2022, Michael Do, Bona Shin, Elaina Lioudis, Emaleigh Munn

Transformative Medicine

This article provides an abbreviated overview of the newly Federal Drug Administration (FDA)approved novel drugs of 2021-2022 with their respective approved indication(s). The FDA serves as the governing body that regularly evaluates and approves medications that will eventually be introduced to the market for routine use. These medications include both drugs that are the same or related to previously approved products (e.g., Extended indications of priorly approved medications) and novel drugs. By definition, a novel drug is an innovative product which serves to improve quality care in patient populations with unmet or advanced medical needs to overall advance patient care …

The Effects Of Cannabidiol On Aqueous Humor Outflow And Trabecular Meshwork Cell Signaling., Alyssa S. Aebersold, Zhao-Hui Song

Faculty and Staff Scholarship

Intraocular pressure (IOP) is regulated primarily through aqueous humor production by ciliary body and drainage through uveoscleral and trabecular meshwork (TM) tissues. The goal of this study was to measure the effect of non-psychotropic cannabidiol (CBD) on aqueous humor outflow through TM and assess the effect of CBD on the TM cell signaling pathways that are important for regulating outflow. Perfused porcine eye anterior segment explants were used to investigate the effects of CBD on aqueous humor outflow. Cultured porcine TM cells were used to study the effects of CBD on TM cell contractility, myosin light chain (MLC) and myosin …

Associations Between Cannabis, Psychosis, And Schizophrenia In Adolescents, Lauren Moment

Academic Leadership Journal in Student Research

The effects of cannabis use on the brain, mind, and body have been studied for decades. The developing brain, particularly the adolescent and young adult brain, undergoes critical development that makes it especially susceptible to the effects of cannabis use. Among the adverse effects of cannabis use in adolescence and young adulthood, psychosis and psychotic disorders (e.g., schizophrenia) have been examined. The association of cannabis use with schizophrenia was first elucidated in a Swedish study of army conscripts. Specifically, conscripts reported their cannabis use exposure and were followed longitudinally to assess the emergence of schizophrenia. The authors found that those …

Who Aware Strategy And Antimicrobial Stewardship To Combat Antimicrobial Resistance: An Indian Perspective, Dinesh K. Meena, Jayanthi Mathaiyan, Geevitha Gauthaman

International Journal of Health and Allied Sciences

Antimicrobial resistance is a serious problem to solve especially in developing countries like India. Antibiotic use in India increased several times since 2005. Many studies in India have reported inappropriate and overuse of antibiotics which could be one of the possible reasons for increased antibiotic resistance in the country. This is an important and urgent issue that mandates strict regulations regarding the rational use of antibiotics. World Health Organization (WHO) has done a major revision to the essential medicines list which classifies antibiotics into three categories (access, watch, and reserve) to ensure the availability and correct use of antibiotics. Several …

Active And Passive Immunization With An Anti-Methamphetamine Vaccine Attenuates The Behavioral And Cardiovascular Effects Of Methamphetamine, Colin N. Haile, Kurt J. Varner, Xia Huijing, Reetakshi Arora, Frank M. Orson, Thomas R. Kosten, Therese A. Kosten

School of Medicine Faculty Publications

Background: Methamphetamine use disorder (MUD) is a growing health concern with no FDA-approved treatment. The present series of studies build upon our previous work developing an anti-methamphetamine (MA) vaccine for MUD. We determined the effects of a formulation that included tetanus-toxoid (TT) conjugated to succinyl-methamphetamine (TT-SMA) adsorbed onto aluminum hydroxide (alum) in combination with the novel Toll-Like Receptor-5 agonist, entolimod. Methods: Mice were vaccinated (0, 3, 6 weeks) with TT-SMA+alum and various doses of entolimod to determine an optimal dose for enhancing immunogenicity against MA. Functional effects were then assessed using MA-induced locomotor activation in mice. Experiments using passive immunization …

Novel Designer Benzodiazepines: Comprehensive Review Of Evolving Clinical And Adverse Effects, Amber N. Edinoff, Catherine A. Nix, Amira S. Odisho, Caroline P. Babin, Alyssa G. Derouen, Salim C. Lutfallah, Elyse M. Cornett, Kevin S. Murnane, Adam M. Kaye, Alan D. Kaye

School of Medicine Faculty Publications

As tranquilizers, benzodiazepines have a wide range of clinical uses. Recently, there has been a significant rise in the number of novel psychoactive substances, including designer benzodiazepines. Flubromazolam(8-bromo-6-(2-fluorophenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazeZpine) is a triazolo-analogue of flubromazepam. The most common effects noted by recreational users include heavy hypnosis and sedation, long-lasting amnesia, and rapid development of tolerance. Other effects included anxiolysis, muscle-relaxing effects, euphoria, loss of control, and severe withdrawals. Clonazolam, or 6-(2-chlorophenyl)-1-methyl-8-nitro-4H-[1,2,4]triazolo[4,3-α]-[1,4]-benzodiazepine, is a triazolo-analog of clonazepam. It is reported to be over twice as potent as alprazolam. Deschloroetizolam (2-Ethyl-9-methyl-4-phenyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine) is part of the thienodiazepine drug class, which, like benzodiazepines, stimulates GABA-A receptors. …

Steap1-4 (Six-Transmembrane Epithelial Antigen Of The Prostate 1-4) And Their Clinical Implications For Prostate Cancer, Michael Xu, Latese Evans, Candice L Bizzaro, Fabio Quaglia, Cecilia E Verrillo, Li Li, Julia Stieglmaier, M J Schiewer, Lucia R Languino, William Kevin Kelly

Department of Urology Faculty Papers

Six-Transmembrane Epithelial Antigen of the Prostate 1-4 (STEAP1-4) compose a family of metalloproteinases involved in iron and copper homeostasis and other cellular processes. Thus far, five homologs are known: STEAP1, STEAP1B, STEAP2, STEAP3, and STEAP4. In prostate cancer, STEAP1, STEAP2, and STEAP4 are overexpressed, while STEAP3 expression is downregulated. Although the metalloreductase activities of STEAP1-4 are well documented, their other biological functions are not. Furthermore, the properties and expression levels of STEAP heterotrimers, homotrimers, heterodimers, and homodimers are not well understood. Nevertheless, studies over the last few decades have provided sufficient impetus to investigate STEAP1-4 as potential biomarkers and therapeutic …

Optimizing Antiretroviral Therapy With Modern Rifapentine Containing Tb Treatment, Anthony T. Podany

Theses & Dissertations

In the past decade there has been a multitude of phase 3 clinical trials targeting treatment shortening for tuberculosis (TB). The synthetic rifamycin derivative rifapentine (RPT) has been at the forefront of many of the treatment shortening approaches. RPT possesses greater potency and a longer pharmacokinetic (PK) half-life (t_1/2) as compared with the long used rifamycin, rifampin (RIF). For TB preventative treatment, a 3-month, once weekly regimen of RPT and isoniazid (INH; 3HP) was shown to be as effective as 9-months of daily INH therapy in the PREVENT TB trial. Similarly, a 4-week course of daily RPT and …

Ondansetron To Reduce Neonatal Opioid Withdrawal Severity: A Randomized Clinical Trial, Gary Peltz, Lauren M. Jansson, Susan Adeniyi-Jones, Carol Cohane, David Drover, Steven Shafer, Meiyue Wang, Manhong Wu, Balaji Govindaswami, Priya Jegatheesan, Cynthia Argani, Salwa Kahn, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Objective
To determine if treatment with a 5-HT3 antagonist (ondansetron) reduces need for opioid therapy in infants at risk for neonatal opioid withdrawal syndrome (NOWS).

Study Design
A multicenter, randomized, placebo controlled, double blind clinical trial of ninety (90) infants. The intervention arms were intravenous ondansetron or placebo during labor followed by a daily dose of ondansetron or placebo in infants for five days.

Results
Twenty-two (49%) ondansetron-treated and 26 (63%) placebo-treated infants required pharmacologic treatment (p>0.05). The Finnegan score was lower in the ondansetron-treated group (4.6 vs. 5.6, p=0.02). A non-significant trend was noted for the duration of …

Establishing The Content Validity Of A Student Pharmacist Patient Counseling Competency Assessment In Oncology, Matthew Newman, Emily Pherson, Bradley Burton, Eric C. Nemec

Physician Associate Studies Faculty Publications

Objective. The main goal of this project was to establish content validity and describe internal consistency of a patient counseling competency assessment instrument used to evaluate student pharmacists practicing in an oncology setting. Methods A modified e-Delphi panel of oncology clinical pharmacy specialists, clinical pharmacy generalists, and oncology pharmacy residents was employed. Iterative rounds of the e-Delphi process were conducted until consensus was reached on a majority of the instrument items. Consensus was defined as agreement by at least 75% of participants that an item was, or was not important. Internal consistency of defined sections of the instrument was determined …

Induced Cytotoxicity In Crebbp/Ep300mut Head And Neck Squamous Cell Carcinoma, Thomaia Pamplin

Dissertations and Theses (Open Access)

INDUCED CYOTOXICTY IN CREBBP/EP300mut HEAD AND NECK SQUAMOUS CELL CARCINOMA

Thomaia Pamplin

Advisor: Curtis Pickering, Ph.D.

Background: Head and neck squamous cell carcinoma HNSCC is the most common malignancy in the head and neck. Most cases are found in advanced stages and depending on the location can be treated with surgical resection and/or radiation (XRT), chemotherapy, or chemoradiation. Our lab groups have identified that HNSCC with a mutation in its CREBBP/EP300 genes can be sensitized to XRT when the histone acetyltransferase activity of CREBBP/EP300 is inhibited. This radiosensitization manifests in the form of increased cell death for …

Visualizing Depressive Symptom Improvement: Implementing The 17-Item Hamilton Depression Rating Scale, Briana Raterman

Dissertations

Visualizing Depressive Symptom Improvement: Implementing the 17-Item Hamilton Depression Rating Scale

Abstract

Problem

Depression, a mental health diagnosis, has affected about 18.5% of adults (Villarroel & Terlizzi, 2020). Ketamine, a medication initially used as an anesthetic, has improved depressive symptoms in individuals struggling with treatment-resistant depression.

Method

This quality improvement (QI) project used the 17-item Hamilton Depression Rating Scale questionnaire to assess depressive symptom changes in patients receiving intramuscular ketamine for treatment-resistant depression. The questionnaire was administered to patients pre-and post-intramuscular ketamine administration. The data was collected on injections one, three, and six on each participant’s set schedule of injections …

Evaluation Of A Process Change Using An Updated Sedation Protocol, Rachel Allen

Dissertations

Problem: Pediatric delirium is continuing to increase intensive care environments and for patients who require mechanical ventilation and continuous sedative medications. Delirium is harmful to the patient creating lasting neurologic and mental health issues along with prolonged hospitalization and increased healthcare cost

Method: For this quality improvement (QI) project, a descriptive observational study was used to evaluate the implementation of a sedation protocol for patients who are mechanically ventilated and on continuous sedative medications. This was completed with the use of retrospective chart reviews three months prior to implementation and three months after the new protocol was implemented. Nurses were …

Pathophysiology Of Aortic Stenosis, Melissa Lee

Nursing Student Class Projects (Formerly MSN)

Pathophysiology of Aortic Stenosis

Melissa J. Lee

Department of Nursing, Otterbein University

NURS 6810: Advanced Pathophysiology for the Advanced Practice Nurse

Dr. Deana Batross & Dr. Shivani Bhatnagar

July 29, 2022

Pathophysiology of Aortic Stenosis

Proper evaluation of co-morbidities is imperative for patient safety and successful outcomes for patients undergoing anesthesia. Aortic stenosis (AS) is one of the most complex diseases encountered in anesthesia, affecting five percent of older adults and ten percent of the 80-89-year-old-cohort (Joseph et al., 2017). The pathophysiological development of AS is the end result of an inflammatory process caused by endothelial damage from mechanical stress, …

Implementation Of An Advanced Operating Room Schedule To Increase Compliance With Clinical Practice Guidelines For Preoperative Antibiotic Selection And Timing: A Quality Improvement Project, Shelby Lynne Adams

Doctor of Nursing Practice Scholarly Projects

Surgical site infection (SSI) is a major cause of morbidity and mortality in operative patients worldwide. The American Society for Health-System Pharmacists (ASHP) published the most recent clinical practice guidelines for antimicrobial prophylaxis in surgery. These guidelines are based upon the available evidence and provide a standardized approach for the safe and effective selection, dosing, and administration of antibiotics for the prevention of SSI (Bratzler et al., 2013). This Doctor of Nursing Practice (DNP) project aimed to determine if incorporating an advanced operating room (OR) schedule, inclusive of ASHP presurgical antibiotics, increased compliance with ASHP standards of antibiotic selection and …

Emicizumab-Kxwh: A Critical Review, Kiera O'Leary

International Undergraduate Journal of Health Sciences

The first descriptions of haemophilia A were reported in the second century AD, with the first modern description by John Conrad Otto in 1803. Historically, the natural history of haemophilia A was associated with very high rates morbidity and mortality, often following trivial accidents. Although treatment options for haemophilia A have been revolutionised in recent decades, haemophilia A remains a hereditary disease of concern and factor replacement products remain the mainstay of treatment.

As such, patients with haemophilia can carry huge burdens, particularly when a complication such as a FVIII inhibitor is present. A recently approved novel therapeutic, Emicizumab-kxwh, has …

A Telehealth-Delivered Tai Chi Intervention (Taichi4joint) For Managing Aromatase Inhibitor-Induced Arthralgia In Patients With Breast Cancer During Covid-19: Longitudinal Pilot Study, Sameh Gomaa, Carly West, Ana Maria Lopez, Tingting Zhan, Max Schnoll, Maysa Abu-Khalaf, Andrew B. Newberg, Kuang-Yi Wen

Department of Medical Oncology Faculty Papers

Background: Estrogen receptor-positive breast cancer is the most common type of breast cancer in postmenopausal women. Aromatase inhibitors (AIs) are the endocrine therapy of choice recommended for these patients. Up to 50% of those treated with an AI develop arthralgia, often resulting in poor adherence and decreased quality of life.

Objective: The study is a single-arm longitudinal pilot study aiming to evaluate the safety, feasibility, acceptability, and potential efficacy of TaiChi4Joint, a remotely delivered 12-week tai chi intervention designed to relieve AI-induced joint pain.

Methods: Women diagnosed with stage 0-III breast cancer who received an AI for at least 2 …