Translational Medical Research Commons^™

Cell-Based Experimental Evidence To The Anti-Covid-19 Potential Of Ashwagandha And Honeybee Propolis Ingredients, Renu Wadhwa, Durai Sundar, Yoshiyuki Ishida, Keiji Terao, Sunil C. Kaul

Research Symposium

Background: The COVID-19 pandemic emerged in December 2019 by a novel strain of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has led to new endeavours in repurposing of existing drugs, anti-COVID-19 vaccine and drug development. Natural products, due to their general safety and wider availability, have attracted research and public attention. In this study, we report anti-COVID potential of compounds from honeybee propolis and Ayurvedic herb, Ashwagandha. Effect of active ingredients was studied on human cell surface receptors (ACE-2:Angiotensin Converting Enzyme-2/Spike protein and TMPRSS2:Transmembrane Protease Serine 2), critical for virus infection and virus main protease (Mpro, essential for virus replication), …

Epicutaneous Sensitization To The Phytocannabinoid Β-Caryophyllene Induces Pruritic Inflammation, Saadet Inan, Sara J Ward, Citlalli T Baltazar, Gabrielle A. Peruggia, Elham Javed, Ajay P. Nayak

Center for Translational Medicine Faculty Papers

In recent years, there has been increased accessibility to cannabis for recreational and medicinal use. Incidentally, there has been an increase in reports describing allergic reactions to cannabis including exacerbation of underlying asthma. Recently, multiple protein allergens were discovered in cannabis, yet these fail to explain allergic sensitization in many patients, particularly urticaria and angioedema. Cannabis has a rich chemical profile including cannabinoids and terpenes that possess immunomodulatory potential. We examined whether major cannabinoids of cannabis such as cannabidiol (CBD) and the bicyclic sesquiterpene beta-caryophyllene (β-CP) act as contact sensitizers. The repeated topical application of mice skin with β-CP at …

Proteomics-Based Approach For Detailing The Allergenic Profile Of Cannabis Chemotypes, Cali Loblundo, Jenna Severa, Gabrielle A Peruggia, Kristina Reid Black, Suman Chandra, Hemant Lata, Mahmoud Elsohly, Martin D Chapman, Deepak A. Deshpande, Ajay P. Nayak

Center for Translational Medicine Faculty Papers

Allergic sensitization to cannabis is an emerging public health concern and is difficult to clinically establish owing to lack of standardized diagnostic approaches. Attempts to develop diagnostic tools were largely hampered by the Schedule I restrictions on cannabis, which limited accessibility for research. Recently, however, hemp was removed from the classified list, and increased accessibility to hemp allows for the evaluation of its practical clinical value for allergy diagnosis. We hypothesized that the proteomic profile is preserved across different cannabis chemotypes and that hemp would be an ideal source of plant material for clinical testing. Using a proteomics-based approach, we …

A Novel Therapeutic Strategy For Alzheimer’S Disease: Sex-Dependent Mechanisms Altered By The Hdac Inhibitor Rg2833 In A Transgenic Rat Model, Kelechi Ndukwe

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is the most common cause of dementia. In the United States, AD affects about 6.2 million Americans and is projected to reach 13.8 million by 2050. Currently, there are no effective therapies for AD and therapies targeting epigenetic mechanisms have shown to be effective in improving cognitive performance in animal models of AD. However, until now no study has reported sex-dependent mechanisms leading to differential expression of genes that contribute to changes in AD pathology. From our in silico studies, we identified an FDA-approved drug, RG2833 (N-[6-(2-aminoanilino)-6-oxohexyl]-4-methylbenzamide) that penetrates the blood brain barrier and can potentially ameliorate …

Evaluation Of A Novel Lupus Anticoagulant Assay Designed To Reduce False Positive Results Due To Anticoagulation: A Retrospective Study At A Single Health System, Jessica D. Anderson, Tamara Sabih, Yuying Xing, Lili Zhao, Marc D. Smith

Conference Presentation Abstracts

Introduction: Lupus anticoagulants (LA) are antibodies directed against phospholipids/phospholipid-protein complexes involved in coagulation and are associated with thrombotic events and recurrent fetal loss. There is no gold standard test for LA, therefore at least two LA-specific tests are recommended before excluding LA. Potential testing methods involve dilute Russell viper venom time (dRVVT) and hexagonal phase phospholipid assays (HPPA); however, many of these tests are susceptible to interference with anticoagulant therapy which can lead to false positive results. In this study, we compared the performance of our current HPPA, StaClot LA (SCLA), with a novel assay reported to have relatively minimal …

Engaging Patients In Opioid Use Disorder Treatment: A Mixed Methods Study Investigating Primary Care Team Perspectives On Approaches, Barriers, And Facilitators, Elizabeth J. Austin, Ulrich Koch, Monica S. Ruiz, Anna D. Ratzliff, Emily C. Williams, Yavar Moghimi

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: Harms from opioid use disorder (OUD) cause significant morbidity and mortality, responsible for over 107,000 overdose-related deaths in 2022 and igniting an urgency to expand access to OUD-related care to new settings such as primary care. A critical element of successful OUD care is engaging patients throughout the OUD care continuum and ongoing retention, yet OUD care engagement rates in outpatient settings are hugely variable, ranging from 4%-70% for initial (14-30 day) treatment engagement, and markedly diminishing over time. The barriers that patients cite to engagement point to the need to deliver more patient-centered OUD care, yet little …

Camkii: A Link Between Metabolic Disorders And Cardiac Arrhythmias, Marilen Federico, C.A. Valverde, L.A. Gonano, J. Palomeque, A. Matiazzi

Center for Translational Medicine Faculty Papers

The prevalence of metabolic diseases -such as obesity, prediabetes, metabolic syndrome or diabetes-has increased globally over the years. These diseases, mainly diabetes mellitus (DM), are among the leading causes of mortality and morbidity worldwide, with increased risk of diabetic cardiomyopathy (DC), cardiac arrhythmias, and heart failure (HF). In metabolic diseases several steps and proteins involved in excitation-contraction coupling (ECC) are compromised, precluding an efficient and rhythmic cardiac contraction; moreover, calcium/calmodulin-dependent protein kinase II (CaMKII) a kinase involved in ECC, is upregulated in several metabolic maladies and significantly contributes to cardiac remodeling and arrhythmias, among which are calcium (Ca2+)-triggered arrhythmias. CaMKII …

The Importance Of Contrast Sensitivity, Color Vision, And Electrophysiological Testing In Clinical And Occupational Settings, Frances Silva

Theses & Dissertations

Visual acuity (VA) is universally accepted as the gold standard metric for ocular vision and function. Contrast sensitivity (CS), color vision, and electrophysiological testing for clinical and occupational settings are warranted despite being deemed ancillary and minimally utilized by clinicians. These assessments provide essential information to subjectively and objectively quantify and obtain optimal functional vision. They are useful for baseline data and monitoring hereditary and progressive ocular conditions and cognitive function. The studies in this dissertation highlight the value of contrast sensitivity, color vision, and cone specific electrophysiological testing, as well as the novel metrics obtained with potential practical clinical …

Prevention And Reversal Of Elastin-Associated And Phosphate-Dependent Arterial Calcification Using Targeted Nanotherapeutics In Pre-Clinical Models, Fatema Tuj Zohora

All Dissertations

Vascular calcification can be life-threatening, involving calcium phosphate crystal deposits in the blood vessels. The calcification in the intimal layer of the arterial wall is usually associated with atherosclerotic plaque build-up that, in the advanced stage, harbors ‘dispersed’ and ‘spotty’ deposits of calcium phosphate crystals in the necrotic core of the plaque. In contrast, medial arterial calcification (MAC) can form independently of atherosclerosis and appears as ‘Railroad-like’ calcific deposits along degraded elastin lamellae in the medial layer of arteries. The mechanisms of such elastin-associated medial arterial calcification and potential therapies are the key concerns of this dissertation. MAC is common …

Isolation Of Therapeutic Antibodies Against Microseminoprotien To Potentially Overcome Resistance To Anti-Angiogenic Therapy, Mason Ruiz

Dissertations and Theses (Open Access)

High-grade serous ovarian carcinoma (HGSC) is an aggressive subtype of epithelial ovarian carcinoma (EOC) and remains the most lethal gynecologic cancer. Angiogenesis is a vital function for both wound healing and oxygen homeostasis and is one of the hallmarks of cancer in solid tumors. To combat the formation of tumors, an anti-VEGF drug, bevacizumab, is used to starve tumors of blood that provide essential nutrients. While platinum-taxane doublet therapy in addition to cytoreductive surgery has been the gold standard treatment for patients with ovarian cancer, greater than 70% of patients will develop relapsed disease and be burdened with a terminal …

Brief Report: Clinical Response, Toxicity, And Resistance Mechanisms To Osimertinib Plus Met Inhibitors In Patients With Egfr-Mutant Met-Amplified Nsclc, Kaiwen Wang, Robyn Du, Sinchita Roy-Chowdhuri, Ziping T Li, Lingzhi Hong, Natalie Vokes, Yasir Y Elamin, Celyne Bueno Hume, Ferdinandos Skoulidis, Carl M Gay, George Blumenschein, Frank V Fossella, Anne Tsao, Jianjun Zhang, Niki Karachaliou, Aurora O'Brate, Claudia-Nanette Gann, Jeff Lewis, Waree Rinsurongkawong, J Jack Lee, Don Lynn Gibbons, Ara A Vaporciyan, John V Heymach, Mehmet Altan, Xiuning Le

Faculty, Staff and Student Publications

INTRODUCTION:MET amplification is a known resistance mechanism to EGFR tyrosine kinase inhibitor (TKI) treatment in EGFR-mutant NSCLC. Dual EGFR-MET inhibition has been reported with success in overcoming such resistance and inducing clinical benefit. Resistance mechanisms to dual EGFR-MET inhibition require further investigation and characterization.

METHODS: Patients with NSCLC with both MET amplification and EGFR mutation who have received crizotinib, capmatinib, savolitinib, or tepotinib plus osimertinib (OSI) after progression on OSI at MD Anderson Cancer Center were included in this study. Molecular profiling was completed by means of fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS). Radiological response …

Abaloparatide Maintains Normal Rat Blood Calcium Level In Part Via 1,25-Dihydroxyvitamin D/Osteocalcin Signaling Pathway, Yanmei Yang, Wei-Ju Louis Tseng, Bin Wang

Center for Translational Medicine Faculty Papers

The PTH-related peptide(1-34) analog, abaloparatide (ABL), is the second anabolic drug available for the treatment of osteoporosis. Previous research demonstrated that ABL had a potent anabolic effect but caused hypercalcemia at a significantly lower rate. However, the mechanism by which ABL maintains the stability of blood calcium levels remains poorly understood. Our in vivo data showed that ABL treatment (40 µg/kg/day for 7 days) significantly increased rat blood level of 1,25-dihydroxyvitamin D [1,25-(OH)2D] without raising the blood calcium value. ABL also significantly augmented the carboxylated osteocalcin (Gla-Ocn) in the blood and bone that is synthesized by osteoblasts, and increased noncarboxylated …

Denoising Cough Sound Recordings Using Neural Networks, Laya Jose, Shlomo Berkovsky, Hao Xiong, Cecilia Mascolo, Roneel V. Sharan

Staff Scholarship - Australia & Dubai

Objective cough sound evaluation is useful in the diagnosis and management of respiratory diseases. However, the performance of cough sound analysis models can degrade in the presence of background noises common in everyday environments. This brings forward the need for cough sound denoising. This work utilizes a method for denoising cough sound recordings using signal processing and machine learning techniques, inspired by research in the field of speech enhancement. It uses supervised learning to find a mapping between the noisy and clean spectra of cough sound signals using a fully connected feed-forward neural network. The method is validated on a …

Neurotropic Manifestations As A Potential Risk Factor For Schizophrenia Following In Utero Exposure To Sars-Cov-2, Mir Ali R Talpur, Omar H. Elsayed, Rif S. El-Mallakh

The University of Louisville Journal of Respiratory Infections

Background: COVID-19 infection is associated with neurologic and psychiatric morbidity that suggests a direct effect of the virus or secondary effect of an inflammatory process. These neuropsychiatric consequences may increase the likelihood of schizophrenia in the offspring of women who become infected with COVID-19 during their pregnancy.

Methods: We performed a directed narrative review of the literature focusing on the proposed pathophysiological processes that lead to schizophrenia and known pathological consequences of COVID-19 infection.

Results: Schizophrenia in adult offspring has been associated with maternal infections during pregnancy by a wide range of respiratory and neurotropic pathogens. Spikes in the incidence …

Interpreting P Values In 2023, Jennifer K. Homa-Bonell

Journal of Patient-Centered Research and Reviews

If recent experiences shared among the biostatistician community are indicative of a sea change in research, then a most-welcome culture shift in dialogue surrounding the proper use and interpretation of the P value, which measures statistical probability, is underway. This editorial strives to offer guidance for researchers who would like to incorporate more comprehensive reporting in their research, namely, a broader discussion that goes beyond looking at the P value by itself and includes effect size estimates, confidence intervals, and clinical implications when interpreting quantitative results. Another evolving development in clinical research is the preferred language when referring …

Calcium Carbonate As A Potential Intervention To Prevent Labor Dystocia: Narrative Review Of The Literature, Sabahat Raees, Marie Forgie, Rita Mitchell, Emily Malloy

Journal of Patient-Centered Research and Reviews

Anecdotally, there are attestations from clinicians of calcium carbonate being used successfully for laboring people experiencing labor dystocia. The goal of this narrative review was to provide a synopsis of pertinent literature on calcium use in obstetrics to explore the potential benefit of calcium carbonate as a simple and low-cost intervention for prevention or treatment of labor dystocia. To answer how calcium and carbonate physiologically contribute to myometrium contractility, we conducted a literature search of English-language peer-reviewed articles, with no year limitation, consisting of the keywords “calcium,” “calcium carbonate,” “calcium gluconate,” “pregnancy,” “hemorrhage,” and variations of “smooth muscle contractility” and …

Identity, Structure, And Function Of The Mitochondrial Permeability Transition Pore: Controversies, Consensus, Recent Advances, And Future Directions, Paolo Bernardi, Christoph Gerle, Andrew P. Halestrap, Elizabeth A. Jonas, Jason Karch, Nelli Mnatsakanyan, Evgeny Pavlov, Shey-Shing Sheu, Alexander A. Soukas

Center for Translational Medicine Faculty Papers

The mitochondrial permeability transition (mPT) describes a Ca2+-dependent and cyclophilin D (CypD)-facilitated increase of inner mitochondrial membrane permeability that allows diffusion of molecules up to 1.5 kDa in size. It is mediated by a non-selective channel, the mitochondrial permeability transition pore (mPTP). Sustained mPTP opening causes mitochondrial swelling, which ruptures the outer mitochondrial membrane leading to subsequent apoptotic and necrotic cell death, and is implicated in a range of pathologies. However, transient mPTP opening at various sub-conductance states may contribute several physiological roles such as alterations in mitochondrial bioenergetics and rapid Ca2+ efflux. Since its discovery decades ago, intensive efforts …

Professionalism And Moral Injury In A Capitalist Healthcare System, James Peter Meza Md, Phd, Kassem Soufan Md, Michael Francis Do, Abbass Berjaoui Md

Clinical Research in Practice: The Journal of Team Hippocrates

Professionalism cautions against profit while capitalism exists for profit. This case is a structural analysis of capitalism in a clinical setting that reveals physicians to be simultaneously wage laborers and professionals. Capitalism generates profit. Professionalism views profit as a conflict of interest that erodes trust in the doctor-patient relationship. Managing these conflicting values causes moral injury for physicians, which is a driver of physician burnout.

Mechanical Thrombectomy For Intermediate Risk Pulmonary Embolism, James Peter Meza, Marissa Costello Md, Angela Moughni Md, Nicholus Yee Md

Clinical Research in Practice: The Journal of Team Hippocrates

An informed consent article using a set of publications to develop an informed consent conversation for a patient with an acute pulmonary embolism being considered for pulmonary artery thrombolysis.

Machine Learning For Ecg Diagnosis And Risk Stratification Of Occlusion Myocardial Infarction, Salah S Al-Zaiti, Christian Martin-Gill, Jessica K Zègre-Hemsey, Zeineb Bouzid, Ziad Faramand, Mohammad O Alrawashdeh, Richard E Gregg, Stephanie Helman, Nathan T Riek, Karina Kraevsky-Phillips, Gilles Clermont, Murat Akcakaya, Susan M Sereika, Peter Van Dam, Stephen W Smith, Yochai Birnbaum, Samir Saba, Ervin Sejdic, Clifton W Callaway

Faculty, Staff and Students Publications

Patients with occlusion myocardial infarction (OMI) and no ST-elevation on presenting electrocardiogram (ECG) are increasing in numbers. These patients have a poor prognosis and would benefit from immediate reperfusion therapy, but, currently, there are no accurate tools to identify them during initial triage. Here we report, to our knowledge, the first observational cohort study to develop machine learning models for the ECG diagnosis of OMI. Using 7,313 consecutive patients from multiple clinical sites, we derived and externally validated an intelligent model that outperformed practicing clinicians and other widely used commercial interpretation systems, substantially boosting both precision and sensitivity. Our derived …