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 …

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 …

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 …

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 …

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 …

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 …

Remifentanil Patient Controlled Analgesia Use In Laboring Women: A Feasibility And Acceptability Study, Joshua Carr

Dissertations

Background/Purpose: Interest in remifentanil patient controlled analgesia (RPCA) as a treatment for labor pain has increased due to its unique pharmacodynamics and effectiveness on pain control among parturients. Despite its promise, RPCA remains infrequently used in the US. The purpose of this study was to 1) examine the implementation and acceptability of a new RPCA protocol in the labor and delivery ward of a mid-sized hospital, and 2) identify the attitudes and beliefs of healthcare workers in a real-world clinical setting.

Theoretical/Conceptual Framework: The holistic nature of Comfort Theory can account for the proposed mechanisms contributing to the …

Decreasing Time To Antibiotic Administration In Febrile Neutropenic Adult Oncology Patients In The Emergency Department: An Evidence-Based Quality Improvement Project, Kristin Murray

DNP Projects

Introduction—Significance and Background: Febrile Neutropenia (FN) is the most common and serious complication of hematopoietic cancers and in patients receiving chemotherapy. Patients in this immunocompromised state have weakened immunity to fight off infection and a mortality rate of almost 10%. Thus, Infectious Diseases Society of America has identified the single most important determining factor of outcomes is the timing of antibiotic (TTA) administration and has identified the gold standard to be 60 minutes. Current practice does not follow guidelines and the current policy does not address the urgency of antibiotic administration.

Purpose: The purpose of this project is to improve …

Targeting Neuronal Nitric Oxide Synthase (Nnos) For Melanoma Treatment, Shirley Tong

Pharmaceutical Sciences (PhD) Dissertations

Human cutaneous melanoma is the most aggressive form of skin cancer and the incidence rates have continued to increase over the years. Neuronal nitric oxide synthase (nNOS) produces nitric oxide (NO) has been found to be overexpressed in human melanoma and the expression of nNOS is induced by interferon-gamma (IFN-γ). In our studies, nNOS has been implicated in IFN-γ-stimulated melanoma progression and the inhibition of nNOS using novel inhibitors effectively inhibited IFN-γ-stimulated tumor growth in a xenograft mouse model. Programmed death-ligand 1 (PD-L1) is overexpressed in melanoma and plays an important role in suppressing the immune system ^12-14. Our …

Non-Opioid Pharmacologic Agents In The Treatment Of Non-Cancer Chronic Pain In The Outpatient Setting, Diane Eannotti

DNP Projects

Opioid prescription related overdose deaths have increased substantially with evidence demonstrating only modest short-term benefits in chronic pain and thus represents the need to identify alternative treatments to opioids. A needs assessment performed for a federally qualified community health center revealed patients presently taking non-opioid pharmacologic agents in the treatment of chronic non-cancer pain (CNCP) needed additional education in managing multiple non-opioid medications. A targeted approach at improving patient experience and population health supporting the quadruple aim was undertaken with this project.

Purpose: The purpose of this quality improvement project consisted of performing medication management visits for 28 referred patients …

Soy Formula Is Not Estrogenic And Does Not Result In Reproductive Toxicity In Male Piglets: Results From A Controlled Feeding Study, Martin J.J. Ronis, Horacio Gomez‐Acevedo, Kartik Shankar, Leah Hennings, Neha Sharma, Michael L. Blackburn, Isabelle Miousse, Harry Dawson, Celine Chen, Kelly E. Mercer, Thomas M. Badger

School of Graduate Studies Faculty Publications

Soy infant formula which is fed to over half a million infants per year contains isoflavones such as genistein, which have been shown to be estrogenic at high concentrations. The developing testis is sensitive to estrogens, raising concern that the use of soy formulas may result in male reproductive toxicity. In the current study, male White‐Dutch Landrace piglets received either sow milk (Sow), or were provided milk formula (Milk), soy formula (Soy), milk formula supplemented with 17‐beta‐estradiol (2 mg/kg/d) (M + E2) or supplemented with genistein (84 mg/L of diet; (M + G) from postnatal day 2 until day 21. …

Targeting Gastrointestinal Cancers With Chimeric Antigen Receptor (Car)-T Cell Therapy, Ross E Staudt, Robert D Carlson, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The immune system is capable of remarkably potent and specific efficacy against infectious diseases. For decades, investigators sought to leverage those characteristics to create immune-based therapies (immunotherapy) that might be far more effective and less toxic than conventional chemotherapy and radiation therapy for cancer. Those studies revealed many factors and mechanisms underlying the success or failure of cancer immunotherapy, leading to synthetic biology approaches, including CAR-T cell therapy. In this approach, patient T cells are genetically modified to express a chimeric antigen receptor (CAR) that converts T cells of any specificity into tumor-specific T cells that can be expanded to …

Partial Treatment Response To Capmatinib In Met-Amplified Metastatic Intrahepatic Cholangiocarcinoma: Case Report & Review Of Literature, Daniel S Lefler, Marni Brisson Tierno, Babar Bashir

Department of Medical Oncology Faculty Papers

Cholangiocarcinoma is a highly morbid gastrointestinal malignancy for which available therapies are limited. Standard of care includes cytotoxic chemotherapies such as gemcitabine, platinum agents, nab-paclitaxel, and fluoropyrimidine analogues. However, tolerability of these regimens varies, and patients who do not tolerate chemotherapy have limited targeted therapies and immunotherapy options. In cholangiocarcinoma, mesenchymal-epithelial transition factor (MET) amplification may present an additional opportunity for a targeted therapeutic approach, especially considering emerging data in non-small cell lung cancer. In this case, we present a metastatic cholangiocarcinoma patient with high-level MET gene amplification for whom capmatinib, a tyrosine kinase inhibitor with activity against c-MET, …

Modified Ysk12-Mend-Sirna In Dendritic Cells For Cancer Immunotherapy, Syed S. Alam

UROP Posters

Tumors may induce tolerogenesis through signaling dendritic cells to produce tolerogenic molecules, such as indoleamine 2, 3-dioxygenase 1 (IDO1). Tumor-associated immunosuppression is associated with higher mortality in patients. Small interfering RNA (siRNA) has been shown to silence specific target genes in the target cell. The siRNA associated with these genes could support a gene knockdown of these immunosuppressors and reduce mortality. Delivery of these therapeutic nucleic acids is difficult in vivo because siRNA is easily broken down inside the cell and the bloodstream through present nucleases. Use of liposome polymers has been reviewed extensively in literature. YSK12-C4, a lipid nanoparticle …

Steroid-Refractory Lichenoid Eruption Associated With Pembrolizumab In A Patient With Non-Small Cell Lung Cancer, Leon Kou, Sanjay Agarwal, Alyssa Miceli, Logan Kolb, Karthik Krishnamurthy, Shawn Schmieder

HCA Healthcare Journal of Medicine

Programmed cell death receptor 1 (PD-1) inhibitors are promising and effective treatments for various cancers. Cutaneous adverse events, such as lichenoid drug eruptions, are well-known common side effects associated with PD-1 inhibitors. Lichenoid drug eruptions associated with PD-1 inhibitors show rapid improvement with high potency topical steroids and do not require cessation of the offending drug. We present the case of an 84-year-old female with progressive pembrolizumab therapy-associated lichenoid eruption that was resistant to several treatments and ultimately required discontinuation of pembrolizumab and treatment with methotrexate to resolve. This report includes histological findings of the pembrolizumab-associated lichenoid eruption.

Editorial: Recent Advances In Cardiotoxicity Testing, Tamer M. A. Mohamed, Javid Moslehi, Jonathan Satin

Physiology Faculty Publications

No abstract provided.

Dextromethorphan-Quinidine Is Helpful For Pseudobulbar Affect Disorder In Stroke Patients, Michael Francis, Mira Hamame, Md, Mariam Nasrallah, Md, Alison Nesbitt, Do, James Peter Meza, Md, Phd

Clinical Research in Practice: The Journal of Team Hippocrates

An informed consent article using

Hammond FM, Alexander DN, Cutler AJ, et al. PRISM II: an open-label study to assess effectiveness of dextromethorphan/quinidine for pseudobulbar affect in patients with dementia, stroke or traumatic brain injury. BMC Neurology. 2016;16:89. https://doi.org/10.1186/s12883-016-0609-0

for a patient with pseudobulbar affect following stroke

Substance Abuse Relapse Is Not About Willpower But Is The Culmination Of Psychological And Socioeconomic Stress, Paul A. Steffes

Clinical Research in Practice: The Journal of Team Hippocrates

The author reflects on the impact of non-judgmental listening on patient care outcomes.

Does Hiv Status Confer A Higher Risk Of Acquiring Covid-19? Using Clinical Decision Science To Combat Patients’ Anxiety, Camilo Guzman

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using

del Amo J, Polo R, Moreno S, et al. “Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving Antiretroviral Therapy.” Annals of Internal Medicine. 2020;173(7):536-541. doi.org/10.7326/m20-3689

for a patient with HIV and concerns about COVID-19 for immunocompromised individuals.

Mental Health Or Cardiac Health. Is There A Reason To Choose? Cardiac Arrhythmias Induced By Atomoxetine And Methylphenidate, Gabriel Cismaru, Viorel Lupu

Journal of Mind and Medical Sciences

The current treatment of Attention Deficit Disorder and Attention Deficit with Hyperactivity consists mainly in the administration of Straterra (Atomoxetine) Concerta and Ritalin (Methylphenidate). The FDA warned that the products might increase systolic, diastolic blood pressure, and lead to ventricular arrhythmias. Arrhythmic events and sudden cardiac death were described in adults with preexistent heart disease. However, studies on children have failed to demonstrate a clear association between the arrhythmic events and these drugs, as demonstrated in adults. What should the attitude of the pediatric psychiatrist be towards the administration of these products? What examination should be made by the psychiatrist …

Decreasing Unintentional Pregnancies For Tennesseans, Paula M. Todd

Electronic Theses and Dissertations

In 2018, 49% of all pregnancies in the United States were unintended, with women with a lower- income status being five times more likely to experience an unplanned pregnancy. Tennessee has a high rate of unintended pregnancies, particularly among the uninsured, low-income, and rural teen populations; some 22% of these unintended pregnancies end in abortion. Oral or transdermal contraceptives that are affordable and accessible for women of childbearing age can reduce unintentional pregnancies. The addressed gap in clinical practice was that contraceptives are not currently available over the counter in Tennessee pharmacies without a prescription, which necessitates a costly medical …

There Is Insufficient Evidence To Recommend Bremelanotide For Hypoactive Sexual Desire Disorder, Scott Yaekle Md, Halima Ali Md, Carol Baker Md

Clinical Research in Practice: The Journal of Team Hippocrates

An informed consent discussion for a patient with Hypoactive Sexual Desire Disorder.

Proof Of Concept: The Use Of Renal Biomarkers In Critically Ill Pediatric Patients For Therapeutic Drug Monitoring, Christopher Lee Shaffer

Theses & Dissertations

Acute kidney injury (AKI) is a serious and common complication in critically ill pediatric patients. The incidence of pediatric AKI continues to increase, especially in patients who undergo surgical correction of congenital heart defects. Serum creatinine and urine output are the most commonly used tools to assess renal function, with international guidelines standardizing AKI-definitions based upon these parameters. However, changes in serum creatinine can occur 24 hours or later after a renal insult event, delaying the diagnosis and potential interventions to reverse injury. It is critical to identify endogenous renal biomarkers within the pediatric population that are both timely and …

Baricitinib In The Treatment Of A Critical Patient With Covid-19 Pneumonia: A Case Report, Nishant Patel, Dylan Goldsmith, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

A 72-year-old male presented to the emergency department with a chief complaint of diarrhea after having tested positive for COVID-19 two days prior. He initially had minimal respiratory complaints, but was eventually transferred to the intensive care unit for acute hypoxic respiratory failure. In addition to dexamethasone, remdesivir, and antibiotics, the patient was treated with baricitinib, a Janus kinase inhibitor that was recently granted emergency use authorization by the Food and Drug Administration for treatment of hospitalized patients with COVID-19. He had an extensive and complicated hospital course and had to be placed on mechanical ventilation, ultimately undergoing tracheostomy. After …

Development Of Vaccines And Antivirals Against Zika Virus, Aryamav Pattnaik

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The re-emergence of Zika virus (ZIKV), an arbovirus, poses a major global human health concern because of its ability to cause congenital abnormalities and neurological diseases. While many candidate vaccines and antiviral drugs are in the developmental pipeline, none have been approved for use against ZIKV infection. This dissertation describes the characterization of one vaccine and two antiviral drug candidates against ZIKV infection. A bacterial ferritin-based nanoparticle vaccine, termed zDIII-F, is designed to display multiple copies of ZIKV E protein domain III on its surface. These stable nanoparticles are shown to induce robust antibody-mediated protection against lethal ZIKV infection in …

Dysregulation Of Systemic Immunity In Aging And Dementia, Jenny Lutshumba, Barbara S. Nikolajczyk, Adam D. Bachstetter

Pharmacology and Nutritional Sciences Faculty Publications

Neuroinflammation and the tissue-resident innate immune cells, the microglia, respond and contribute to neurodegenerative pathology. Although microglia have been the focus of work linking neuroinflammation and associated dementias like Alzheimer’s Disease, the inflammatory milieu of brain is a conglomerate of cross-talk amongst microglia, systemic immune cells and soluble mediators like cytokines. Age-related changes in the inflammatory profile at the levels of both the brain and periphery are largely orchestrated by immune system cells. Strong evidence indicates that both innate and adaptive immune cells, the latter including T cells and B cells, contribute to chronic neuroinflammation and thus dementia. Neurodegenerative hallmarks …