Medicine and Health Sciences Commons^™

Electrophysiological Properties Of The Mitochondrial Permeability Transition Pores: Channel Diversity And Disease Implication., M. A. Neginskaya, E. V. Pavlov, S.-S. Sheu

Center for Translational Medicine Faculty Papers

The mitochondrial permeability transition pore (mPTP) is a channel that, when open, is responsible for a dramatic increase in the permeability of the mitochondrial inner membrane, a process known as the mitochondrial permeability transition (mPT). mPTP activation during Ca2+ dyshomeostasis and oxidative stress disrupts normal mitochondrial function and induces cell death. mPTP opening has been implicated as a critical event in many diseases, including hypoxic injuries, neurodegeneration, and diabetes. Discoveries of recent years indicate that mPTP demonstrates very complicated behavior and regulation, and depending on specific induction or stress conditions, it can function as a high-conductance pore, a small channel, …

The Er Stress/Upr Axis In Chronic Obstructive Pulmonary Disease And Idiopathic Pulmonary Fibrosis., Mahmoud Aghaei, Sanaz Dastghaib, Sajjad Aftabi, Mohamad-Reza Aghanoori, Javad Alizadeh, Pooneh Mokarram, Parvaneh Mehrbod, Milad Ashrafizadeh, Ali Zarrabi, Kielan Darcy Mcalinden, Mathew Suji Eapen, Sukhwinder Singh Sohal, Pawan Sharma, Amir A Zeki, Saeid Ghavami

Center for Translational Medicine Faculty Papers

Cellular protein homeostasis in the lungs is constantly disrupted by recurrent exposure to various external and internal stressors, which may cause considerable protein secretion pressure on the endoplasmic reticulum (ER), resulting in the survival and differentiation of these cell types to meet the increased functional demands. Cells are able to induce a highly conserved adaptive mechanism, known as the unfolded protein response (UPR), to manage such stresses. UPR dysregulation and ER stress are involved in numerous human illnesses, such as metabolic syndrome, fibrotic diseases, and neurodegeneration, and cancer. Therefore, effective and specific compounds targeting the UPR pathway are being considered …

Modelling Cross-Disciplinary Integration In Fda Multidisciplinary And Interdisciplinary Reviews For New Drug Products: A Phenomenological Descriptive Comparative Case Study, Kevin Bugin

Doctor of Philosophy in Translational Health Sciences Dissertations

Cross-disciplinary integration is a key feature of interdisciplinary research and the collaborative form is often one of the desired outcomes of Team Science endeavors. In 2019 the FDA began rolling out a new interdisciplinary approach to their cross-disciplinary assessment of marketing applications, with the key feature being integrated, collaborative review documents (Woodcock et al., 2020). FDA’s assessment of new drug products to allow them to enter the marketplace is a critical translational activity to protect the US public’s health that requires team-based integration and transparency (Woodcock, 2018). And, while increased cross-disciplinary integration through enhanced collaboration and communication is sought through …

Healthcare Workers Hospitalized With Covid-19: Outcomes From The Burden Of Covid-19 Study At The University Of Louisville Center Of Excellence For Research In Infectious Diseases [Cerid], Ruth Carrico, T'Shura S. Ali, Maria Hill, Lucia B. Puga Sanchez, Catherine M. Bryan, Dawn Balcom, Stephen P. Furmanek, Amr Aboelnasr, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Introduction: On March 6, 2020, the current ongoing pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as COVID-19, reached the commonwealth of Kentucky. Within days, the first cases of infection and hospitalization were identified among healthcare workers (HCW) in Kentucky, other states in the U.S., and around the world. There is little information available regarding the impact of COVID-19 on the HCW population within this area. The objective of this study was to describe the baseline characteristics of hospitalized HCWs infected with COVID-19.

Methods: Data collection was performed as part of a retrospective study of patients hospitalized …

Covid-19 & Pregnancy Complication During Early Pandemic: A Narrative Review, Ahmed A. Eladely, Maria Hill, Ahmed Abdelhaleem, Zahid Imran, Ahsan M. Khan, Daisy Sangroula

The University of Louisville Journal of Respiratory Infections

Background: Coronaviruses have caused three outbreaks in the past two decades. The novel one is SARS-COV-2, which causes COVID-19. Pregnant women have a somewhat altered immune state, which may make them more vulnerable to COVID-19 and its complications. Extensive research is needed to better understand the clinical course of COVID-19 in this population. This review article discusses the comparison of SARS-CoV-2 with previous coronavirus outbreaks, clinical presentations, and complications in pregnant women and newborns.

Methods: We conducted a literature search for case series and case reports about pregnancy outcomes in pregnant women with COVID-19 during the early phase of pandemic. …

The Case Of A Pregnant Woman With Ards Due To Covid-19 Treated With Hydroxychloroquine, Azithromycin, And Remdesivir And Delivery Of A Healthy Baby During Mechanical Ventilation Through Cesarean Section, Adria Madera-Acosta, Martin Gnoni, Bassman Tappuni, Monika Sadlak, Ravleen Grewal, Angel Mena, Yousef Ali-Ahwel

The University of Louisville Journal of Respiratory Infections

We are in the midst of a pandemic due to SARS-CoV-2. Pregnancy was identified among the risk factors for worse clinical outcomes in multiple studies. The optimal therapy in this group of patients remains to be defined. Here, we present the case of a 39-year-old Caucasian pregnant female at 31 weeks of gestation, who was treated successfully with hydroxychloroquine, azithromycin, remdesivir, prone therapy, and cesarean delivery of a healthy baby while on mechanical ventilation. She remained SARS-CoV-2-positive until the 39th day of hospitalization. We discuss the pathophysiology of the increased risk of infections during pregnancy and particularly the high risk …

Low-Dose Psoralen–Uv-A Maintenance Therapy Prolongs Disease-Free Remission Rates In Mycosis Fungoides Patients, Joshua M. Brady

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using Vieyra-Garcia P, Fink-Puches R, Porkert S, et al. Evaluation of Low-Dose, Low-Frequency Oral Psoralen–UV-A Treatment With or Without Maintenance on Early-Stage Mycosis Fungoides. JAMA Dermatology. 2019;155(5):538. https://doi.org/10.1001/jamadermatol.2018.5905 for a patient weighing whether to continue treatment in light of socioeconomic circumstances.

Translating Evidence-Based Guidelines Into Practice—Are We Getting It Right? A Multi-Centre Prospective International Audit Of Nutrition Care In Patients With Foregut Tumors (Inform), Merran Findlay, Judith D. Bauer, Rupinder Dhaliwal, Marian De Van Der Schueren, Alessandro Laviano, Adrianne Widaman, Lisa Martin, Andrew G. Day, Leah M. Gramlich

Faculty Research, Scholarly, and Creative Activity

Malnutrition is highly prevalent in patients with foregut tumors comprising head and neck (HNC) and esophageal (EC) cancers, negatively impacting outcomes. International evidence-based guidelines (EBGs) for nutrition care exist; however, translation of research evidence into practice commonly presents considerable challenges and consequently lags. This study aimed to describe and evaluate current international nutrition care practices compared with the best-available evidence for patients with foregut tumors who are at high risk of malnutrition. A multi-centre prospective cohort study enrolled 170 patients commencing treatment of curative intent for HNC (n = 119) or EC (n = 51) in 11 cancer …

Implementation Of The University Of Louisville Covid-19 Biorepository: Experiences From The Center Of Excellence In Infectious Diseases (Cerid), Dawn Balcom, Leslie A Wolf, Subathra Marimuthu, William Johnson, Danial Malik, Chet Dhakal, Pavani Nathala, Mohammed Abbas, Sahaj Hardeep Singh, Basel Haddad, Rafik Elbeblawy, Fnu Deepti, Ahmed Ali, Evelyn Exposito Gonzalez, Ruth Carrico

The University of Louisville Journal of Respiratory Infections

The limited availability of biological samples from patients testing positive for SARS-CoV-2 for future research was quickly identified at the onset of the COVID-19 pandemic. In response to this need, a COVID-19 biobank was initiated by the University of Louisville Division of Infectious Diseases, Center of Excellence for Research in Infectious Diseases (CERID). The COVID-19 biobank contains waste samples obtained from patients hospitalized with COVID-19 in any of the nine Louisville, Kentucky, area hospitals during the timeframe of April 13 to September 20, 2020. The COVID-19 biobank stores approximately 1,623 waste samples with 2,127 aliquots for distribution. All samples are …

Characteristics And Outcomes Of Adults Hospitalized With Sars-Cov-2 Community-Acquired Pneumonia In Louisville, Kentucky, Julio A. Ramirez, Jose Bordon, Rodrigo Cavallazzi, Stephen P. Furmanek, Amr Aboelnasr, Mahder A. Tella, William A. Mattingly, Ashley M. Wilde, Daisy Sangroula, Demetra Antimisiaris, Donghoon Chung, Guillermo Cabral, Gabino R Fernandez-Botran, Jiapeng Huang, Martin Gnoni, Ozan Akca, Paul Schulz, Phillip F. Bressoud, Priya Krishnan, Sally Suliman, Sathya Krishnasamy, Stephen S. Hanson, William P. Mckinney, Harpal Sandhu, Leslie A Wolf, Mark Burns, Ruth Carrico, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

Background: Patients infected with the novel coronavirus SARS-CoV-2 are frequently hospitalized with community-acquired pneumonia (CAP). The objective of this study was to define the clinical characteristics and outcomes of hospitalized patients with SARS-CoV-2 CAP in the city of Louisville, KY.

Methods: This was a retrospective observational study of 700 patients with SARS-CoV-2 infection hospitalized at eight of the adult hospitals in the city of Louisville. Patients with 1) a positive RT-PCR for SARS-CoV-2, 2) fever, cough, or shortness of breath, and 3) an infiltrate on chest imaging were defined as having SARS-CoV-2 CAP. Demographic characteristics of the study population were …

Development Of A Pediatric Cardiac Assist Maglev Pump For Use With A Universal Driver System., Landon Heath Tompkins

Electronic Theses and Dissertations

Heart failure (HF) remains the leading cause of death, affecting 26 million adults worldwide and 6.5 million adults in the United States. Pediatric HF patients have been a historically underserved population with few options for mechanical circulatory support (MCS) therapy, a leading treatment as an alternative to heart transplantation. To address this clinical need, the Inspired Universal MagLev System is being developed; a low cost, universal magnetically levitated extracorporeal MCS system with interchangeable single-use pumps that will ultimately provide adult and pediatric patients ventricular and respiratory assist therapies. The Inspired Pediatric VAD is the first single-use pump application for this …

Validation Of An Inertial-Measurement-Unit System For Calculating Hip And Knee Flexion Angles During Gait, Joonsun Park

Master's Theses

Technological advances regarding Inertial Measurements Units (IMUs) have positioned this type of sensor as an alternative for camera-based motion capture. This study introduces a new IMU based system (IMU_sys) to measure hip and knee flexion angles. PURPOSE: To validate the use of a five-sensor IMU_sys for the measurement of knee and hip flexion angles during gait in adults and pediatrics at two different time points. METHODS: Bilateral hip and knee flexion patterns (LH, RH, LK, and RK) of twenty-two healthy participants (12 adults and 10 pediatric) between the ages of 8 – 35 years were investigated. Participants …

A Narrative Review On The Basic And Clinical Aspects Of The Novel Sars-Cov-2, The Etiologic Agent Of Covid-19., Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Girish C. Shukla, Mudit Tyagi

Center for Translational Medicine Faculty Papers

The novel SARS-CoV-2 is responsible for causing the ongoing outbreak of coronavirus disease 19 (COVID-19), a systemic infection in humans. Ever since it was first detected in December 2019, the number of confirmed cases has continued to increase. Within a short period, this disease has become a global issue, and therefore it is characterized as a pandemic. The current understanding and explanations are based on epidemiological, clinical and physiological observations. Besides, it remains a great challenge, as much remains to be understood about this new disease-causing virus. Therefore, we seek to provide an overview of SARS-CoV-2, including its classification, origin, …

Great Expectations: Phosph(On)Ate Prodrugs In Drug Design—Opportunities And Limitations, Victoria Yan

Dissertations & Theses (Open Access)

Phosphate and phosphonates are chemical moieties with historical precedence in anticancer and antiviral nucleotide analogues. Synchronous to modern efforts identifying novel therapeutic targets in cancer, such chemical moieties are being investigated in the design of novel inhibitors with antineoplastic potential. A central challenge to the delivery of phosph(on)ate-containing drugs is their anionic character at physiological pH, which portends poor membrane permeability. This limitation has been successfully overcome through the use of prodrugs. When attached to the phosph(on)ate moiety, prodrugs mask the negative charge and easily enable cell permeability. Upon cellular entry, the promoieties are enzymatically or environmentally cleaved to unveil …

Combined Inhibition Of Ddr1 And Cdk4/6 Induces Synergistic Effects In Er-Positive, Her2-Negative Breast Cancer With Pik3ca/Akt1 Mutations, Maryam Shariati, Maryam Shariati

Dissertations & Theses (Open Access)

COMBINED INHIBITION OF DDR1 AND CDK4/6 INDUCES SYNERGISTIC EFFECTS IN ER-POSITIVE, HER2-NEGATIVE BREAST CANCER WITH PIK3CA/AKT1 MUTATIONS

Maryam Shariati, M.S. Advisory Professor: Funda Meric-Bernstam, M.D.

Molecular alterations in the phosphatidylinositol 3‑kinase (PI3K)/ serine/threonine protein kinase B (AKT) signaling pathway occur frequently in estrogen receptor–positive (ER-positive) breast tumors. Patients with ER-positive, human epidermal growth factor receptor 2–negative (HER2-negative) metastatic breast cancer are often treated with cyclin-dependent kinase (CDK4/6) inhibitors such as palbociclib in combination with endocrine therapy. Although this is a very effective regimen, disease progression ultimately occurs in most patients. Further, the modulators of palbociclib sensitivity remain unclear. The purpose …

Age, Comorbidities, And Mortality Correlation In Covid-19 Patients: A Review, Vidyulata Salunkhe, Amr Aboelnasr, Parul Pahal, Nida Qadir, Simra Kiran, Balaji Sekaran, Omar Fahmy, Farah Daas, Syed Shah

The University of Louisville Journal of Respiratory Infections

Background: The risk of death due to COVID-19 among hospitalized patients is known to be higher in older adults and those with underlying health conditions. Understanding the proportion of patients who are at increased risk of death due to COVID-19 and how this varies between age groups will inform the healthcare community as to how to evaluate the risk of COVID-19 and better design healthcare and economic policies.

Methods: We conducted a literature search for studies published between December 2019 and May 16, 2020 in PubMed, Embase, and Cochrane (CENTRAL). Descriptive statistics were performed.

Results: We reviewed 14 studies, of …

Effect Of An Intervention To Improve Smoking Cessation Treatment In A Federally Qualified Healthcare Clinic, Shirley A. Camp

The Corinthian

Abstract

Significant progress has been made in the reduction of tobacco use in the United States, but the smoking prevalence among the socially and economically disadvantaged populations (i.e. individuals who are homeless, uninsured, LGBT, and living with HIV) is significantly higher than the general population (CDC, 2018b). As a result, these vulnerable populations carry a disproportionate burden of tobacco-related mortality and morbidity (CDC, 2018b). There is a cost-effective and evidence-based treatment for tobacco use dependence (Fiore et al, 2008), but the delivery by primary care providers to this population is inconsistent (Tyman, Bonevski, Paul, & Bryant, 2014). This study focused …

Medical Social Science And Clinical Decision Science, James Peter Meza

Clinical Research in Practice: The Journal of Team Hippocrates

Exploring the curricular link between Medical Social Science and Clinical Decision Science in the development of a physician.

The Odorant Receptor Or2w3 On Airway Smooth Muscle Evokes Bronchodilation Via A Cooperative Chemosensory Tradeoff Between Tmem16a And Cftr., Jessie Huang, Hong Lam, Cynthia Koziol-White, Nathachit Limjunyawong, Donghwa Kim, Nicholas Kim, Nikhil Karmacharya, Premraj Rajkumar, Danielle Firer, Nicholas M Dalesio, Joseph Jude, Richard C Kurten, Jennifer L Pluznick, Deepak A. Deshpande, Raymond B Penn, Stephen B Liggett, Reynold A Panettieri, Xinzhong Dong, Steven S An

Center for Translational Medicine Faculty Papers

The recent discovery of sensory (tastant and odorant) G protein-coupled receptors on the smooth muscle of human bronchi suggests unappreciated therapeutic targets in the management of obstructive lung diseases. Here we have characterized the effects of a wide range of volatile odorants on the contractile state of airway smooth muscle (ASM) and uncovered a complex mechanism of odorant-evoked signaling properties that regulate excitation-contraction (E-C) coupling in human ASM cells. Initial studies established multiple odorous molecules capable of increasing intracellular calcium ([Ca2+]i) in ASM cells, some of which were (paradoxically) associated with ASM relaxation. Subsequent studies showed a terpenoid molecule (nerol)-stimulated …

Congregate Care In The Time Of Covid-19: Proposed Best Practices From The Inside, Linda Bergthold, Margan Zajdowicz, Thaddeus R. Zajdowicz, Elli Hall, Kimberley A. Buckner, Ruth Carrico

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Conference Proceedings: Aurora Scientific Day 2020

Journal of Patient-Centered Research and Reviews

Abstracts published in this supplement were among those presented at the 46th annual Aurora Scientific Day research symposium, held virtually on May 20, 2020. The symposium provides a forum for describing research studies conducted by faculty, fellows, residents, and allied health professionals affiliated with Wisconsin-based Aurora Health Care, a part of the Advocate Aurora Health health system, which publishes the Journal of Patient-Centered Research and Reviews.

Action Items For Breast Cancer Awareness Month, Deanna J. Attai

Journal of Patient-Centered Research and Reviews

This special issue introduction provides a brief history of Breast Cancer Awareness Month and focuses on patient populations often omitted from annual marketing campaigns. The importance of research is emphasized as a means to improve the outcomes of people with metastatic breast cancer and male breast cancer as well as to address health care inequities related to breast cancer diagnosis and treatment.

Simvastatin Induces Unfolded Protein Response And Enhances Temozolomide-Induced Cell Death In Glioblastoma Cells., Sanaz Dastghaib, Shahla Shojaei, Zohreh Mostafavi-Pour, Pawan Sharma, John B Patterson, Afshin Samali, Pooneh Mokarram, Saeid Ghavami

Center for Translational Medicine Faculty Papers

Glioblastoma (GBM) is the most prevalent malignant primary brain tumor with a very poor survival rate. Temozolomide (TMZ) is the common chemotherapeutic agent used for GBM treatment. We recently demonstrated that simvastatin (Simva) increases TMZ-induced apoptosis via the inhibition of autophagic flux in GBM cells. Considering the role of the unfolded protein response (UPR) pathway in the regulation of autophagy, we investigated the involvement of UPR in Simva-TMZ-induced cell death by utilizing highly selective IRE1 RNase activity inhibitor MKC8866, PERK inhibitor GSK-2606414 (PERKi), and eIF2α inhibitor salubrinal. Simva-TMZ treatment decreased the viability of GBM cells and significantly increased apoptotic cell …

Cancer Detection In Radical Prostatectomy Histology Using Convolutional Neural Networks, Laurie Huang

Electronic Thesis and Dissertation Repository

Radical prostatectomy (RP) is a common treatment for prostate cancer. We used RP whole-mount tissue samples from 68 patients stained with haematoxylin and eosin to create cancer maps using four pretrained networks: AlexNet, NASNet, VGG16 and Xception, to classify regions of interest (ROIs) as cancer or non-cancer. Models were trained on either raw images or as tissue component maps (TCMs) containing nuclei, lumina and stroma/other components generated from a trained U-Net.

All models performed similarly; however, VGG16 trained on raw images performed with the highest area under the receiver operating characteristic curve (AUC) of 0.994 (95% confidence interval 0.992-0.996). Ensemble …

Il-1 Inhibitor Anakinra Is An Effective Alternative To Standard Treatments For Reducing Pain Due To Acute Gout Flare, Cheryl Craig

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising Janssen CA, Voshaar MAHO, Vonkeman HE, et al. Anakinra for the treatment of acute gout flares: a randomized, double-blind, placebo-controlled, active-comparator, non-inferiority trial. Rheumatology. 2019;58(8):1344-1352. https://doi.org/10.1093/rheumatology/key402 for a patient with an acute gouty attack refractory to standard treatment.

Clinical Approach To A Request For Phentermine-Topiramate In A Young Woman With A History Of High-Risk Eating Behavior, Erin Spencer

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising Safer DL, Adler S, Dalai SS, et al. A randomized, placebo-controlled crossover trial of phentermine-topiramate ER in patients with binge-eating disorder and bulimia nervosa. Int J Eat Disord. 2019;(September):1-12. https://doi.org/10.1002/eat.23192 to inform the clinical decision of whether or not to prescribe phentermine-topiramate to an overweight 27-year-old woman who endorses risky eating behaviors.

Medication Assisted Treatment With Buprenorphine/Naloxone Or Methadone: Comparitive Outcomes In Patients With An Opioid Addiction, Deepti Shanbhag

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising Hser YI, Evans E, Huang D, et al. Long‐term outcomes after randomization to buprenorphine/naloxone versus methadone in a multi‐site trial. Addiction. 2016;111(4):695-705. https://doi.org/10.1111/add.13238 for a patient with addiction to prescription opioids.

Cyclosporine Shows Benefit As Compared To Methotrexate For Treatment Of Pediatric Atopic Dermatitis Refractory To Topical Medications When Rapidity Of Clinical Response Is Of Key Importance To The Patient, Connor R. Buechler, Steven Daveluy Md

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising El-Khalawany MA, Hassan H, Shaaban D, Ghonaim N, Eassa B. Methotrexate versus cyclosporine in the treatment of severe atopic dermatitis in children: a multicenter experience from Egypt. European Journal of Pediatrics. 2012;172(3):351-356. https://doi.org10.1007/s00431-012-1893-3 for a pediatric patient with severe atopic dermatitis.

Myomectomy Has Better Reproductive Outcomes Than Uterine Artery Embolization For Patients With Symptomatic Leiomyomas Who Wish Maintain Fertility, Suha Syed

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising Mara M, Maskova J, Fucikova Z, Kuzel D, Belsan T, Sosna O. Midterm clinical and first reproductive results of a randomized controlled trial comparing uterine fibroid embolization and myomectomy. Cardiovascular and interventional radiology. 2008;31(1):73-85. https://doi.org/10.1007/s00270-007-9195-2

Little Is Known About Cannabidiol For Improving Severe Behavioral Symptoms Of Autistic Spectrum Disorder, Keerteshwrya Mishra

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising Barchel D, Stolar O, De-Haan T, et al. Oral cannabidiol use in children with autism spectrum disorder to treat related symptoms and co-morbidities. Frontiers in Pharmacology. 2019;9. https://doi.org/10.3389/fphar.2018.01521