Translational Medical Research Commons^™

Communicating Unexpected Genetic Information With Family Members: A Multimethod Study Of Secondary Findings Recipients, Julie Chevalier Sapp

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: Medically-actionable secondary genomic findings (SF) can be life- preserving or life-prolonging for recipients but this benefit can only extend to family members if this information is shared with relatives. How SF recipients communicate this important genetic information with relatives, barriers and facilitators to this process, and SF recipients’ lived experiences in communicating about their results over time remain largely unknown. Family communication is required for relatives of SF recipients to access cascade testing and the potential benefits of enhanced screening and management. Applying behavioral and implementation science theories and providing rich and deep descriptions of SF recipients’ lived experiences …

Virtual Education Implementation For Children With Autism Spectrum Disorders Amidst The Covid-19 Pandemic, Monika Sinha-Bhamra

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: The COVID-19 pandemic led to widespread school closures in the Washington DC metropolitan region, necessitating a shift from traditional in-person education to virtual platforms. The context was significantly influenced by the evolving pandemic and its impact on the region's COVID-19 positive rates, with the Washington DC region facing some of the highest positive rates in 2020. These escalating positive rates posed substantial challenges to planning and implementing in-person learning, primarily driven by concerns for public health and safety. The region's persistently low percentages of in-person learning made it one of the worst in the country regarding the provision of …

Tox3 Rs3803662 Polymorphism Is Associated With Breast Cancer Protection In Northeastern Mexican Woman, Orlando D. Solis-Coronado, Hazyadee F. Rodríguez-Gutiérrez, Monica P. Villarreal-Vela, Ricardo M. Cerda-Flores, Juan F. González-Guerrero, Oscar Vidal-Gutiérrez, Diana C. Pérez-Ibave, Maria Lourdes Garza-Rodríguez

Research Symposium

Introduction: Low penetrance genes are involved in breast cancer (BC) and confer risk for the development of this neoplasia. Different single nucleotide polymorphisms (SNPs) associated with BC have been identified, such as rs3803662 (TOX3), which is related to estrogen receptors in European and African-American women. The contribution of this variant in the Mexican population is unknown. The objective of this study was to evaluate, through a case-control design, the association of the SNP rs3803662 (TOX3), with the risk of BC in women from northeastern Mexico.

Methods: We included 434 cases and 228 controls. Genotyping was carried out using RFLPs. The …

Smoking And Drinking Activates Nf-Κb /Il-6 Axis To Promote Inflammation During Cervical Carcinogenesis, Vivek Kumar Kashyap, Prashanth Kb Nagesh, Ajay K. Singh, Andrew Massey, Godwin P. Darkwah, Murali M. Yallapu, Meena Jaggi, Subhash C. Chauhan

Research Symposium

Background: High-risk strains of HPV are known to cause cervical cancer. Multiple clinical studies have emphasized that smoking and drinking are critical risk factors for cervical cancer and its high-grade precursors. In this study, we investigated the molecular mechanisms involved in the interplay of smoking and/or drinking with HPV infectivity and defined a systematic therapeutic approach for their attenuation in cervical cancer.

Methods: The impact of benzo[a]pyrene (B[a]P) and/or ethanol (EtOH) exposure on cervical cancer cells was assessed by measuring changes in cell proliferation, clonogenicity, biophysical properties, cell migration, and invasion. Expression of HPV16 E6/E7, NF-κB, cytokines, cell cycle, and …

Human Ipsc Derived Cardiomyocyte Model Reveals The Transcriptomic Bases Of Covid-19 Associated Myocardial Injury, Kashish Kumar, Satish Kumar, Erica De Leon, Joanne E. Curran, Sarah Williams-Blangero, John Blangero

Research Symposium

Background: Multi-organ complications have been the hallmark of severe COVID-19; cardiac injuries were reported in 20% to 30% of hospitalized COVID-19 patients, although the disease etiology remains poorly understood. This study leveraged genome-wide RNA-sequence data generated using induced pluripotent stem cell (iPSC) differentiated cardiomyocytes (CMs) and in vitro modeling of SARS-CoV-2 infection in CMs, to understand the molecular mechanisms of COVID-19 myocardial injuries for novel diagnostic and therapeutic development.

Methods: Raw RNA-sequence data sets, GSE165242 and GSE150392 were aligned to human genome assembly GRCh38 and gene expressions were quantified. Differentially expressed (DE) genes between experimental groups were identified using moderated …

Differential Gene Expression Between African American And Caucasian American Prostate Cancer, Daniel L. Shen, Gregory T. Maclennan, Sanjay Gupta

Research Symposium

Background: African-American (AA) men have higher incidence and mortality from prostate cancer compared to Caucasian-American (CA) men. Increasing evidence suggests that genetic and molecular alterations play important roles. We identified a 5 gene panel viz. p-Akt (Ser473), chemokine (C-X-C motif) receptor 4 (CXCR4), fatty acid synthase (FASN), interleukin-6 (IL-6) and matrix metallopeptidase 9 (MMP-9) highly expressed in prostate cancer and analyzed their expression in AA and CA cohorts.

Methods: IHC of p-Akt, CXCR4, FASN, IL-6 and MMP-9 were evaluated in RRP specimens (n=20) from each ethnic group exhibiting Gleason scores ranging from 6 through 9.

Results: Low to medium staining …

An Ngqd Based Diagnostic Tool For Pancreatic Cancer, Ryan Ketan Ajgaonkar, Bong Lee, Alina Valimukhametova, Anton Naumov, Giridhar Akkaraju

Research Symposium

Background: Pancreatic cancer remains difficult to detect at early stages which contributes to a poor five-yearsurvival rate. Therefore, early detection approaches based on novel technologies should be explored to address this critical health issue. Nanomaterials have recently emerged as frontrunners for diagnostic applications due to their small size in the 1-100 nm range, which facilitates one-on-one interactions with a variety of biomolecules like oligonucleotides and makes them suitable for a plethora of detection and delivery applications. In this work, the presence of specific pancreatic cancer miRNA (pre-miR-132) is detected utilizing the fluorescence properties of highly biocompatible nitrogen-doped graphene quantum dots …

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 …

Is Having Difficulty Meeting The Recommended Physical Activity Guidelines Associated With Cognitive Difficulties In Us Adults?, Serena C.L. Buchwald, Daniel Gitelman, Noël C. Barengo, Pura Rodríguez De La Vega

AMNET XX Conferencia Internacional

This abstract summarizes and gives a brief overview of our analytical research study on the associations of meeting physical activity guidelines and cognitive difficulties such as difficulty remembering/concentrating.

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 …

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 …

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 …

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 …

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 …

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 …

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 …

Shedding Light On Hearing In Coma: Investigating The Applicability Of Functional Near-Infrared Spectroscopy For Assessing Auditory Function And Aiding Prognosis In Patients With Acute Disorders Of Consciousness, Reza Moulavi Ardakani

Electronic Thesis and Dissertation Repository

There is a critical need for a bedside neuroimaging tool to aid in the prediction of functional recovery outcomes for patients with acute disorders of consciousness (DoC) in the early days following severe brain injury. Current neurobehavioral examinations and prognosis tools have limitations in predicting good outcomes, leading to potential mistreatment or premature withdrawal of life support. Functional near-infrared spectroscopy (fNIRS) is a viable candidate for such purposes due to its portability and cost-effectiveness. Auditory processing, viewed as a multi-level and multifaceted brain function, could provide a sensitive and specific marker of residual cognitive function in unresponsive patients. This study …

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.

The Effect Of Kidney Preservation At 10°C With Hemopure And Hydrogen Sulfide Donor, Sodium Thiosulfate, In A Syngeneic Model Of Rat Renal Transplantation, Maria Abou Taka

Electronic Thesis and Dissertation Repository

Kidney transplantation is preferred for patients with end-stage renal disease. The current gold standard for preserving kidneys is static cold storage (SCS) at 4°C in University of Wisconsin (UW) solution. However, SCS contributes to ischemia-reperfusion injury (IRI), which involves cell death and inflammation. Our group showed that SCS of kidneys with hydrogen sulfide donors, like sodium thiosulfate (STS), that reduce tissue injury enhanced kidney survival. Though, there is still a risk of cold renal IRI at 4°C. Recent evidence suggests that preserving organs at 10°C enhanced graft function and survival. Therefore, this thesis will evaluate the effect of 10°C kidney …

On The Respiratory Syncytial Virus Vaccine, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Increased Glucose Availability Sensitizes Pancreatic Cancer To Chemotherapy, Ali Vaziri-Gohar, Jonathan J. Hue, Ata Abbas, Hallie J. Graor, Omid Hajihassani, Mehrdad Zarei, George Titomihelakis, John Feczko, Moeez Rathore, Sylwia Chelstowska, Alexander W. Loftus, Rui Wang, Mahsa Zarei, Maryam Goudarzi, Renliang Zhang, Belinda Willard, Li Zhang, Adam Kresak, Joseph E. Willis, Gi-Ming Wang, Curtis Tatsuoka, Joseph M. Salvino, Ilya Bederman, Henri Brunengraber, Costas A. Lyssiotis, Jonathan R. Brody, Jordan M. Winter

Student Papers, Posters & Projects

Pancreatic Ductal Adenocarcinoma (PDAC) is highly resistant to chemotherapy. Effective alternative therapies have yet to emerge, as chemotherapy remains the best available systemic treatment. However, the discovery of safe and available adjuncts to enhance chemotherapeutic efficacy can still improve survival outcomes. We show that a hyperglycemic state substantially enhances the efficacy of conventional single- and multi-agent chemotherapy regimens against PDAC. Molecular analyses of tumors exposed to high glucose levels reveal that the expression of GCLC (glutamate-cysteine ligase catalytic subunit), a key component of glutathione biosynthesis, is diminished, which in turn augments oxidative anti-tumor damage by chemotherapy. Inhibition of GCLC phenocopies …

Implementation Barriers Of Multidisciplinary Care In Chronic Kidney Disease Through A Cfir Framework: A Narrative Review, Max J. Goodman, Amalia Jereczek

Cooper Rowan Medical Journal

Introduction: 37 million Americans suffer from chronic kidney disease, which affects multiple organ systems and requires multidisciplinary care. Multidisciplinary care is an inherently broad and complex topic, and while it is being implemented across healthcare in the United States and abroad, multidisciplinary care outcomes are poor in this patient population. It is possible that there exists gaps in the literature regarding implementation and replication of multidisciplinary care interventions such that healthcare practices are unable to fully take advantage of multidisciplinary care publications for chronic kidney disease. This narrative review utilizes the five domains of the Consolidated Framework for Implementation Research …

Comparison Of The Biological Basis For Non-Hiv Transmission To Hiv-Exposed Seronegative Individuals, Disease Non-Progression In Hiv Long-Term Non-Progressors And Elite Controllers, Joseph Hokello, Priya Tyagi, Shelly Dimri, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

HIV-exposed seronegative individuals (HESIs) are a small fraction of persons who are multiply exposed to human immunodeficiency virus (HIV), but do not exhibit serological or clinical evidence of HIV infection. In other words, they are groups of people maintaining an uninfected status for a long time, even after being exposed to HIV several times. The long-term non-progressors (LTNPs), on the other hand, are a group of HIV-infected individuals (approx. 5%) who remain clinically and immunologically stable for an extended number of years without combination antiretroviral therapy (cART). Meanwhile, elite controllers are comprise a much lower number (0.5%) of HIV-infected persons …

Apoe4, Age, And Sex Regulate Respiratory Plasticity Elicited By Acute Intermittent Hypercapnic-Hypoxia, Jayakrishnan Nair, Joseph F. Welch, Alexandria B. Marciante, Tingting Hou, Qing Lu, Emily J. Fox, Gordon S. Mitchell

Department of Physical Therapy Faculty Papers

Rational

Acute intermittent hypoxia (AIH) shows promise for enhancing motor recovery in chronic spinal cord injuries and neurodegenerative diseases. However, human trials of AIH have reported significant variability in individual responses.

Objectives

Identify individual factors (eg, genetics, age, and sex) that determine response magnitude of healthy adults to an optimized AIH protocol, acute intermittent hypercapnic-hypoxia (AIHH).

Methods

In 17 healthy individuals (age = 27 ± 5 yr), associations between individual factors and changes in the magnitude of AIHH (15, 1-min O2 = 9.5%, CO2 = 5% episodes) induced changes in diaphragm motor-evoked potential (MEP) amplitude and inspiratory mouth occlusion pressures …

Crosstalk Between Diacylglycerol Kinase And Protein Kinase A In The Regulation Of Airway Smooth Muscle Cell Proliferation, Miguel Angel Hernandez-Lara, Santosh Kumar Yadav, Stanley Conaway, Sushrut D. Shah, Raymond B. Penn, Phd, Deepak A. Deshpande, Phd

Center for Translational Medicine Faculty Papers

Background: Diacylglycerol kinase (DGK) regulates intracellular signaling and functions by converting diacylglycerol (DAG) into phosphatidic acid. We previously demonstrated that DGK inhibition attenuates airway smooth muscle (ASM) cell proliferation, however, the mechanisms mediating this effect are not well established. Given the capacity of protein kinase A (PKA) to effect inhibition of ASM cells growth in response to mitogens, we employed multiple molecular and pharmacological approaches to examine the putative role of PKA in the inhibition of mitogen-induced ASM cell proliferation by the small molecular DGK inhibitor I (DGK I).

Methods: We assayed cell proliferation using CyQUANT™ NF assay, protein expression …

A Review Of Isomirs In Colorectal Cancer, Molly A. Lausten, Bruce M. Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

As advancements in sequencing technology rapidly continue to develop, a new classification of microRNAs has occurred with the discovery of isomiRs, which are relatively common microRNAs with sequence variations compared to their established template microRNAs. This review article seeks to compile all known information about isomiRs in colorectal cancer (CRC), which has not, to our knowledge, been gathered previously to any great extent. A brief overview is given of the history of microRNAs, their implications in colon cancer, the canonical pathway of biogenesis and isomiR classification. This is followed by a comprehensive review of the literature that is available on …

Building Up Cal Poly Global Brigades Student Group: Reflections On Designing And Implementing One Undergraduate-Led Community Info Session, Caroline Nicole Smith, Jafra D. Thomas

Kinesiology and Public Health

Intro: Global Brigades, an international non-profit organization, trains college students and other pre-professionals in community-based health promotion by mobilizing community service trips around the world, which are taught and led by local community groups. Cal Poly’s Global Brigades student group was founded in 2018, and thus far, they have carried out three annual, medically-focused brigades to Honduras (two in-person, one virtual).

Purpose: The aim of this report is to present the findings of one experiential senior project to promote Cal Poly’s Global Brigades student group^[1] (conducted January to March 2023).

Methods: The student designed material for …

Integrative Analysis Of Metabolome And Methylome Identifies The Correlation Of Aminoacyl-Trna Biosynthesis Metabolitesand Sepsecs Gene Methylation In Huntington’S Disease Brain Tissue, Sangeetha Vishweswaraiah, Ali Yilmaz, Nadia Ashrafi, Nazia Saiyed, Abdulla Khalid, Purvesh R. Koladiya, Xiaobei Pan, Shirin Macias, Uppala Radhakrishna, Stewart F. Graham

Conference Presentation Abstracts

No abstract provided.