Translational Medical Research Commons^™

Leveraging Bio-Inspired Molecules For Cancer Theranostics, Douglas S. Macpherson

Dissertations, Theses, and Capstone Projects

A variety of molecules can be radiolabeled and delivered to a cancer site for the purposes of diagnostics and therapy. Among the most promising of tumor targeting molecules are peptides and antibodies. These bio-inspired molecules can be designed and synthesized to target and respond to cancer cells based on the properties of those cells. Matrix metalloproteinase (MMP) enzymes are over-expressed by some metastatic cancers, in which they are responsible for the degradation and remodeling of the extracellular matrix. In recent years, MMPs have emerged as promising targets for enzyme-responsive diagnostic probes because oligopeptides can be designed to be selectively hydrolyzed …

Mst1-Mediated Phosphorylation Of Nur77 Improves The Endometrial Receptivity In Human And Mice, Xinyu Cai, Yue Jiang, Zhiwen Cao, Mei Zhang, Na Kong, Lina Yu, Yedong Tang, Shuangbo Kong, Wenbo Deng, Haibin Wang, Jianxin Sun, Lijun Ding, Ruiwei Jiang, Haixiang Sun, Guijun Yan

Center for Translational Medicine Faculty Papers

Background: Successful embryo implantation requires the attachment of a blastocyst to the receptive endometrial epithelium, which was disturbed in the women with recurrent implantation failure (RIF). Endometrial β3-integrin was the most important adhesion molecule contributing to endometrial receptivity in both humans and mice. Nur77 has been proven indispensable for fertility in mice, here we explore the role of Nur77 on embryo-epithelial adhesion and potential treatment to embryo implantation failure.

Methods: The expression and location of Mst1 and Nur77 in endometrium from fertile women and RIF patients were examined by IHC, qRT-PCR and Western blotting. In vitro kinase assay following with …

The Neuroadvocacy Toolkit: A Knowledge Translation Strategy To Strengthen Food Fortification Policies To Prevent Neural Tube Defects In Latin American Countries. A Mixed-Method Study, Kemel A. Ghotme

Doctor of Philosophy in Translational Health Sciences Dissertations

Background. Neural tube defects are one of the leading congenital malformations that affect children in Latin America and worldwide, leading to pregnancy terminations, morbidity, mortality, and long-term disability. The most cost-effective and equitable way to prevent them is by implementing public health policies for food fortification with folic acid. However, a lack of knowledge translation strategies partly accounts for the incomplete enactment, enforcement, and scaling-up of mandatory fortification. There is no evidence in the scientific literature of studies attempting to identify the factors contributing to the development and implementation of knowledge translation strategies aiming to influence policymakers’ decisions regarding mandatory …

An Entosis-Like Process Induces Mitotic Disruption In Pals1 Microcephaly Pathogenesis, Noelle A Sterling, Jun Young Park, Raehee Park, Seo-Hee Cho, Seonhee Kim

Center for Translational Medicine Faculty Papers

Entosis is cell cannibalism utilized by tumor cells to engulf live neighboring cells for pro- or anti-tumorigenic purposes. It is unknown whether this extraordinary cellular event can be pathogenic in other diseases such as microcephaly, a condition characterized by a smaller than normal brain at birth. We find that mice mutant for the human microcephaly-causing gene Pals1, which exhibit diminished cortices due to massive cell death, also exhibit nuclei enveloped by plasma membranes inside of dividing cells. These cell-in-cell (CIC) structures represent a dynamic process accompanied by lengthened mitosis and cytokinesis abnormalities. As shown in tumor cells, ROCK inhibition completely …

Cocaine Sensitizes The Cd4+ T Cells For Hiv Infection By Co-Stimulating Nfat And Ap-1, Adhikarimayum Lakhikumar Sharma, Dylan Shafer, Daniel Netting, Mudit Tyagi

Center for Translational Medicine Faculty Papers

The productive infection of HIV, which generates new viral progeny, depends on the activation status of the cell. In this study, we found cocaine exposure sensitizes partially active CD4+ T cells and makes them poised for productive HIV infection. We discovered that cocaine treatment enhances the metabolic state of the cells by co-stimulating several transcription factors, mainly NFAT and AP-1, the two transcription factors, which specifically play a crucial role in enhancing both HIV and the overall cellular gene expression in T cells. We found that cocaine-induced AP-1 works in tandem with NFAT to boost HIV transcription. The enhanced HIV …

Understanding The Contributions Of Hormonal Contraceptives And Cortisol Levels To Fear Learning In Women, Sahil Bardai

Symposium of Student Scholars

Women are twice as likely to be diagnosed with an anxiety disorder than men. Eighty-five percent of women in the US will use hormonal contraceptives at some point in their lifetime. Women who use hormonal contraceptives show heightened startle reactivity to a threatening stimulus. Previous results from our lab showed a significant increase in fear-potentiated startle (FPS) in women who were on hormonal contraceptives compared to women who were naturally cycling. These results stayed consistent throughout three acquisition trials. Others have shown that the use of OCPs (oral contraceptive pills) is related to the dysregulation of the HPA-axis and elevated …

Bioprosthetic Reoperative Aortic Valve Replacement In Patients Under 50, Aisha Kazeem

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Chan V, Lam BK, Rubens FD, et al. Long-term evaluation of biological versus mechanical prosthesis use at reoperative aortic valve replacement. J Thorac Cardiovasc Surg. 2012;144(1):146-151. https://doi.org/10.1016/j.jtcvs.2011.08.041

for a patient considering reoperative aortic valve replacement.

Renal Replacement Therapy Could Be Initiated In Patients With Severe Aki, Regardless Of Age And Critical Condition, El Hussain Shamsa

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Meersch M, Küllmar M, Schmidt C, et al. Long-Term Clinical Outcomes after Early Initiation of RRT in Critically Ill Patients with AKI. J Am Soc Nephrol. Mar 2018;29(3):1011-1019. https://doi.org/10.1681/asn.2017060694

for a critically ill elderly patient with severe acute kidney injury.

The Effect Of Medical Respite Services On Hospital Readmissions For Those Experiencing Homelessness, Kendrick Belardo

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Kertesz SG, Posner MA, O’Connell JJ, et al. Post-Hospital Medical Respite Care and Hospital Readmission of Homeless Persons. J Prev Interv Community. 2009;37(2):129-142. https://doi.org/10.1080/10852350902735734

for a patient experiencing homelessness.

The Use Of Cold Dialysis Solution In Reducing Fatigue In An End-Stage Renal Disease Patient, Justin Pawloski

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Sajadi M, Gholami Z, Hekmatpour D, Soltani P, Haghverdi F. Cold dialysis solution for hemodialysis patients with fatigue ‐ a cross‐over study. Iranian Journal of Kidney Diseases. 2016;10(5):319‐24.

for a patient with sickle cell disease.

Self-Administered Opat (S-Opat) Is A Potential Cost-Effective Equivalent Option For Uninsured Patients Requiring Opat, Joshua Brady

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Bhavan KP, Brown LS, Haley RW. Self-Administered Outpatient Antimicrobial Infusion by Uninsured Patients Discharged from a Safety-Net Hospital: A Propensity-Score-Balanced Retrospective Cohort Study. PLoS Med. 2015;12(12): e1001922. https://doi.org/10.1371/journal.pmed.1001922

for a patient with fungal peritonitis requiring OPAT.

Cystic Fibrosis Transmembrane Conductance Regulator Modulation May Improve Intestinal Inflammation In Adults With Cystic Fibrosis, Lauren G. Culver

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Ooi CY, Syed SA, Rossi L, Garg M, Needham B, Avolio J, Young K, Surette MG, Gonska T. Impact of CFTR modulation with Ivacaftor on Gut Microbiota and Intestinal Inflammation. Sci Rep. 2018 Dec 13;8(1):17834. https://doi.org/10.1038/s41598-018-36364-6

for a patient with cystic fibrosis experiencing small bowel obstruction.

Partial Outpatient Oral Antibiotic Treatment Of Infective Endocarditis Is Non-Inferior To Inpatient Intravenous Antibiotic Therapy, Nicholas J. Murphy

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Iversen K, Ihlemann N, Gill SU, et al. Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. N Engl J Med. 2019; 380:415-424. https://doi.org/10.1056/NEJMoa1808312

for a patient with infective endocarditis and intravenous drug use with desire to leave the hospital.

Baclofen As A Helpful Alternative In Treatment Of Painful Paroxysmal Attacks From Trigeminal Neuralgia, Samantha Ryan

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Fromm GH, Terrance CF, Chattha AS. Baclofen in the treatment of trigeminal neuralgia: double-blind study and long-term follow-up. Ann Neurol. 1984;15(3):240. https://doi.org/10.1002/ana.410150306

for a patient with paroxysmal attacks from trigeminal neuralgia who is unable to take carbamazepine.

Indwelling Pleural Catheterization Maximizes Functionality And Quality Of Life In Management Of Recurrent Malignant Pleural Effusions, Avinash Ramkissoon

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: The TIME2 randomized controlled trial. J Am Med Assoc. 2012;307(22):2383-2389. https://doi.org/10.1001/jama.2012.5535

for the management of recurrent malignant pleural effusions in a patient with metastatic renal cell carcinoma.

Exploring Alternative Treatment Options For A Patient With Heavy Menstrual Bleeding And Mistrust Of The Healthcare System, Rachel A. O'Dell

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Tinelli A, Gustapane S, D’Oria O, Licchelli M, Panese G. Nutraceuticals in fibroid management after ulipristal acetate administration: An observational study on patients’ compliance. International Journal of Gynecology and Obstetrics; 2022;156(1):133-138. https://doi.org/10.1002/ijgo.13692

for a patient with chronic, symptomatic anemia with menorrhagia and uterine fibroid.

The Importance Of Stigma Theory For Clinical Decisions Related To Diabetic Foot Amputations, Rachael Garcia, Callie Bartkowiak, Alison Nesbitt Do

Clinical Research in Practice: The Journal of Team Hippocrates

The authors examine the unconsidered impact of social stigma theory on the shared clinical decision-making process for a patient with foot osteomyelitis and MRSA bacteremia facing the prospect of an amputation.

Piperine Attenuates Cigarette Smoke-Induced Oxidative Stress, Lung Inflammation, And Epithelial-Mesenchymal Transition By Modulating The Sirt1/Nrf2 Axis, Pritam Saha, Sneha Durugkar, Siddhi Jain, P A Shantanu, Samir R Panda, Aishwarya Jala, Sharad Gokhale, Pawan Sharma, V G M Naidu

Center for Translational Medicine Faculty Papers

Piperine (PIP) is a major phytoconstituent in black pepper which is responsible for various pharmacological actions such as anti-inflammatory, antioxidant, and antitumor activity. To investigate the effects and mechanisms of PIP on cigarette smoke (CS)-induced lung pathology using both in-vitro and in-vivo models. BEAS-2B and A549 cells were exposed to CS extract (CSE) for 48 h; BALB/c mice were exposed to CS (9 cigarettes/day, 4 days) to induce features of airway disease. PIP at doses of (0.25, 1.25, and 6.25 µM, in vitro; 1 and 10 mg/kg, in vivo, i.n) and DEX (1 µM, in vitro; 1 mg/kg, in vivo, …

A Moment Of Reflection As We Move Forward, Bruce Morgenstern

Journal of Patient-Centered Research and Reviews

The newly appointed editor-in-chief of the Journal of Patient-Centered Research and Reviews reflects on the original editorial mission of the journal and its continuing commitment to publish patient-centered scholarly works that exhibit respect for each patient’s values and preferences; coordinated and integrated care; patient and family education; alleviation of pain, fear, and anxiety; continuity through care-site transitions; and access to care. The reasoning behind the pursuit of well-developed patient-centered care models, through the dissemination of peer-reviewed research findings and patient perspectives, has only been reinforced since the journal’s launch in 2014.

Understanding How Social Determinants Of Health Are Integrated Within Clinical Decision Science, James Peter Meza Md, Phd, Nicholus H. Yee Md

Clinical Research in Practice: The Journal of Team Hippocrates

The editors reflect on the effect of Social Determinants of Health in Clinical Decision Science on questions of efficacy and effectiveness.

The Decision I Never Thought I Would Have To Make, Mary Nixon

Clinical Research in Practice: The Journal of Team Hippocrates

A brief essay on how the COVID pandemic has changed how we think about medicine and our patients.

Regulation Of Airway Smooth Muscle Cell Proliferation By Diacylglycerol Kinase: Relevance To Airway Remodeling In Asthma, Miguel Angel Hernandez-Lara, Santosh K Yadav, Sushrut D. Shah, Mariko Okumura, Yuichi Yokoyama, Raymond B. Penn,, Taku Kambayashi, Deepak A. Deshpande

Center for Translational Medicine Faculty Papers

Airway remodeling in asthma involves the hyperproliferation of airway smooth muscle (ASM) cells. However, the molecular signals that regulate ASM growth are not completely understood. Gq-coupled G protein-coupled receptor and receptor tyrosine kinase signaling regulate ASM cell proliferation via activation of phospholipase C, generation of inositol triphosphate (IP3) and diacylglycerol (DAG). Diacylglycerol kinase (DGK) converts DAG into phosphatidic acid (PA) and terminates DAG signaling while promoting PA-mediated signaling and function. Herein, we hypothesized that PA is a pro-mitogenic second messenger in ASM, and DGK inhibition reduces the conversion of DAG into PA resulting in inhibition of ASM cell proliferation. We …

What? Is Epstein–Barr Virus Infection Linked To Multiple Sclerosis?, Asha Mahajan, Steven B Lippmann

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Anxiolytics For Bronchodilation: Refinements To Gaba, Ajay P Nayak, Steven S An

Department of Medicine Faculty Papers

No abstract provided.

Introducing A Physical Therapist-Led Acceptance And Commitment Therapy Training For Pain: A Clinical Perspective, Joseph Tatta

Internet Journal of Allied Health Sciences and Practice

Purpose: Mounting evidence supports the use of cognitive and behavioral techniques as part of physical therapist practice. These methods are used within a physical therapist’s multimodal treatment approach for the management of pain and to facilitate health behavior change. There is a multitude of evidence-based cognitive behavioral techniques to choose from including newer approaches based on Acceptance and Commitment Therapy. Yet few studies have examined physical therapists’ perceptions to learning and implementing ACT into clinical practice. The purpose of this manuscript is to present a clinical perspective of physical therapists learning about and incorporating Acceptance and Commitment Therapy in clinical …

Do You Know The Pathophysiology Of Cytokine Storm During Covid-19?, Shameera Shaik Masthan, Deekshitha Turaka, Ahmed Abdelhaleem, Mounica Vorla, Steven B. Lippmann

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Evaluation Of Respiratory Function Using Blood Gas Parameters In Yucatan Minipigs Following Spinal Cord Injury, Jackson Gallagher, Monique Morgan, Chase Knibbe, Destiny Gibson, Maxwell Boakye

The Cardinal Edge

There are approximately 17,810 new spinal cord injuries (SCI) in the U.S. each year [1]. Physical damage to the spinal cord has the potential to interfere with normal motor, sensory, and/or autonomic function, such as impairment of the respiratory system. In fact, respiratory insufficiency is the number one cause of mortality and morbidity after SCI. The more rostral the injury, the more likely there will be disruption to normal ventilation (generally rostral to T6) [2]. To conduct relevant preclinical research, it has been shown that large animal models, such as the Yucatan minipig, have a better success rate of translating …

Improving Governance In Ontario Health Teams, Mausam Vadakkayil

Undergraduate Student Research Internships Conference

The aim of this research brief is to provide recommendations on how Ontario Health Teams (OHTs) can incorporate the three key functions of successful health systems, priority setting, performance monitoring, and accountability, within their governance structure.

Comparing Outcomes For Community-Acquired Pneumonia Between Females And Males: Results From The University Of Louisville Pneumonia Study, Pavani Nathala, Simrat Sarai, Vidyulata Salunkhe, Mahder A. Tella, Stephen P. Furmanek, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

Introduction: Male sex is currently considered to be a risk factor for worsened community-acquired pneumonia (CAP) outcomes compared to female sex; hence, female sex equates to a lower score on the Pneumonia Severity Index. There is no recent update on sex-based outcomes of patients with CAP. The objective of this study was to compare the outcomes of CAP between females and males.

Methods: This was a secondary analysis of the University of Louisville Pneumonia Study database. It was a prospective population-based cohort study of all hospitalized adults with CAP who were residents of Jefferson County in the city of Louisville, …

Grk2 Regulates Adp Signaling In Platelets Via P2y1 And P2y12., Xuefei Zhao, Matthew Cooper, James V Michael, Yanki Yarman, Aiden Baltz, J Kurt Chuprun, Walter J Koch, Steven E. Mckenzie, Maurizio Tomaiuolo, Timothy J Stalker, Li Zhu, Peisong Ma

Department of Medicine Faculty Papers

The critical role of G protein-coupled receptor kinase 2 (GRK2) in regulating cardiac function has been well documented for >3 decades. Targeting GRK2 has therefore been extensively studied as a novel approach to treating cardiovascular disease. However, little is known about its role in hemostasis and thrombosis. We provide here the first evidence that GRK2 limits platelet activation and regulates the hemostatic response to injury. Deletion of GRK2 in mouse platelets causes increased platelet accumulation after laser-induced injury in the cremaster muscle arterioles, shortens tail bleeding time, and enhances thrombosis in adenosine 5'-diphosphate (ADP)-induced pulmonary thromboembolism and in FeCl3-induced carotid …