Translational Medical Research Commons^™

Pkcε Activator Protects Hippocampal Microvascular Disruption And Memory Defect In 3×Tg-Alzheimer's Disease Mice With Cerebral Microinfarcts, Huaixing Wang, Zongxiu Zhang, Jarin Hongpaisan

Center for Translational Medicine Faculty Papers

BACKGROUND: Current evidence suggests that microvessel disease is involved in Alzheimer's disease (AD). Cerebrovascular disease correlates with cardiovascular disease and is complicated in ≈40% of AD patients. The protein kinase C (PKC) ε activator DCPLA can stimulate human antigen (Hu) R that prevents degradation and promotes the translation of mitochondrial Mn-superoxide dismutase (MnSOD) and vascular endothelial growth factor-A (VEGF) mRNAs.

METHODS: To induce brain microinfarcts, we injected triple transgenic (3×Tg) and wild-type (WT) control mice with microbeads (20 μm caliber) into common carotid arteries, with or without the DCPLA-ME (methyl-ester) for 2 weeks. After water maze training, mice at 16 …

Interleukin 31 Receptor Α Promotes Smooth Muscle Cell Contraction And Airway Hyperresponsiveness In Asthma, Santhoshi Akkenepally, Dan Yombo, Sanjana Yerubandi, Geereddy Bhanuprakash Reddy, Deepak Deshpande, Francis Mccormack, Satish Madala

Center for Translational Medicine Faculty Papers

Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness (AHR), inflammation, and goblet cell hyperplasia. Multiple cytokines, including IFNγ, IL-4, and IL-13 are associated with asthma; however, the mechanisms underlying the effects of these cytokines remain unclear. Here, we report a significant increase in the expression of IL-31RA, but not its cognate ligand IL-31, in mouse models of allergic asthma. In support of this, IFNγ, IL-4, and IL-13 upregulated IL-31RA but not IL-31 in both human and mice primary airway smooth muscle cells (ASMC) isolated from the airways of murine and human lungs. Importantly, the loss of IL-31RA …

Reactive Oxygen Species Behaving Badly: Oxidized Phosphatidylcholines Corrupt Ca2+ Signaling In Airway Smooth Muscle, Deepak A. Deshpande, Raymond B. Penn

Center for Translational Medicine Faculty Papers

No abstract provided.

Standardized Total Fitness Scores And Phase Angle In Cancer Survivors, Paulette Yamada, Trevor Short

Topics in Exercise Science and Kinesiology

Topics in Exercise Science and Kinesiology Volume 4: Issue 1, Article 20, 2023. Cancer treatment can lead to decrement in all components of fitness. Exercise can attenuate these effects and build fitness. Exercise program design for this population continues to evolve with high-intensity interval training at the forefront. Phase angle (PhA) is an indirect measure of cellular health and function and is associated with fitness, health, and reduced disease severity. Continued exploration spurs an emerging question: What type of training should be used to maximize improvements in PhA? We provide a visualization of a cancer rehabilitation fitness profile and present …

Sex And Gender Differences In Arthritis Health Information, Tania Al-Jilawi

Electronic Thesis and Dissertation Repository

Arthritis is a common disorder that may result in pain and inflammation, making it challenging to move or continue being active. Arthritis comes in a variety of forms. The two studies of this thesis aimed to identify the influence of intersectionality, especially sex and gender, in arthritis. The first study, a structured review, evaluated the inclusion of sex/gender and intersectional identities in patient resources of three arthritis societies: the Canadian Arthritis Society, the American Arthritis Foundation, and the National Rheumatoid Arthritis Society. The appraisal tool, the Sex/Gender and Intersectional Considerations in Patient/Consumer Health Information Appraisal Tool was used to evaluate …

Promoting Mammography Screenings In African American Women: Media, Church, And Health Providers, Lasonya Little, Debra C. Wallace, K.Jay Poole

Journal of Health Disparities Research and Practice

Due to the underutilization of screening mammography, African American women (AAW) are more likely to experience negative health outcomes after receiving a late-stage breast cancer diagnosis than White Women (WW). The purpose of this article is to examine the roles of the media, health community and the African American church and pastor and their potential impact in AAW screening decisions. Fifteen AAW, ages 45 and older, were invited to participate in a semi-structured interview. Most women agreed the African American pastor and church as well as the health community, and media are an integral part of their lives. Therefore, specific …

An American Medical Economics Phenomenon, Richard Guthmann Md, Mph

Clinical Research in Practice: The Journal of Team Hippocrates

The author reflects on his own experience with medical economics-driven phenomena in healthcare.

Increase In Hnrnpa1 Expression Suffices To Kill Motor Neurons In Transgenic Rats, Xionghao Liu, Tingting Zhang, Qinxue Wu, Cao Huang, Xu-Gang Xia, Hongxia Zhou, Bo Huang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A dominant mutation in hnRNPA1 causes amyotrophic lateral sclerosis (ALS), but it is not known whether this mutation leads to motor neuron death through increased or decreased function. To elucidate the relationship between pathogenic hnRNPA1 mutation and its native function, we created novel transgenic rats that overexpressed wildtype rat hnRNPA1 exclusively in motor neurons. This targeted expression of wildtype hnRNPA1 caused severe motor neuron loss and subsequent denervation muscle atrophy in transgenic rats that recapitulated the characteristics of ALS. These findings demonstrate that the augmentation of hnRNPA1 expression suffices to trigger motor neuron degeneration and the manifestation of ALS-like phenotypes. …

Immune Responses Induced At One Hour Post Cataract Surgery Wounding Of The Chick Lens, Jodirae Dedreu, Morgan Basta, Janice Walker, Sue Menko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

While the lens is an avascular tissue with an immune-privileged status, studies have now revealed that there are immune responses specifically linked to the lens. The response to lens injury, such as following cataract surgery, has been shown to involve the activation of the resident immune cell population of the lens and the induction of immunomodulatory factors by the wounded epithelium. However, there has been limited investigation into the immediate response of the lens to wounding, particularly those induced factors that are intrinsic to the lens and its associated resident immune cells. Using an established chick embryo ex vivo cataract …

Social Determinants May Limit The Success Of Pcsk9 Inhibitors, An Effective Treatment For Hyperlipidemia In Statin-Intolerant Patients, Abigail C. Kuplicki

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Moriarty PM, Thompson PD, Cannon CP, et al. Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: The ODYSSEY ALTERNATIVE randomized trial. J. Clin. Lipidol. 2015;9(6):758-769. https://doi.org/10.1016/j.jacl.2015.08.006

for a statin-intolerant patient with hyperlipidemia.

Renal Disease Rehabilitation And Delaying Dialysis, Spencer Brown, Natalie Sterner

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Greenwood SA, Koufaki P, Mercer TH, et al. Effect of exercise training on estimated GFR, vascular health, and cardiorespiratory fitness in patients with CKD: a pilot randomized controlled trial. Am J Kidney Dis. 2015;65(3):425-434. https://doi.org/10.1053/j.ajkd.2014.07.015

for a patient with non-dialysis CKD interested in slowing the progression toward necessary dialysis.

Slow Surgical Correction Affects More Than Just The Bowels, Emilia M. Clementi

Clinical Research in Practice: The Journal of Team Hippocrates

Reflection on how delayed colostomy reversal affects a patient's mental and physical well-being.

Whole Genome-Based Dna Methylation Profiling In Covid-19 Patients Reveals Alterations In Pathways Linked To Neurological Dysfunctions, Syed Zami, Juozas Gordevicius, Eman Anis, Qiong Sha, Martha L. Escobar Galvis, Michael Henderson, Andrew Pospisilik, Patrik Brundin, Stewart Graham

Conference Presentation Abstracts

The sever acute respiratory syndrome corona virus 2 (SARS-CoV-2) is a highly transmissible viruswhich causes a life-threatening illness called coronavirus (COVID-19). It has cost millions ofdeath worldwide. This novel RNA betacorona virus is manifested by varying clinical symptomsranging from asymptomatic to mild to severe systemic illness with deadly outcomes. Muchevidence revealed the differences in the severity of COVID-19 infection varied widely accordingto host factors and comorbidities. It is critical to understand the interplay of genetic and epigeneticfactors and host response to this fatal virus. A substantial number of epigenome-wide associationstudies acknowledged that SARS-CoV-2 manipulate the host epigenome via DNA methylation …

Uptitrating Mycophenolate Mofetil Therapy In A Patient With Lupus Cerebritis Doesn’T Increase Risk Of Infection Compared To Cyclophosphamide, Gautham Pavar

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising

Appel GB, Contreras G, Dooley MA, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol. 2009;20(5):1103-1112. https://doi.org/10.1681/ASN.2008101028

for a patient with neuropsychiatric lupus.

Stigma And Patient-Controlled Analgesia: Trust Is The Essential Ingredient Of Successful Patient Education In The Patient-Doctor Relationship, Trey D. Vanaken

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Van Beers EJ, Van Tuijn CFJ, Nieuwkerk PT, et al. Patient-controlled analgesia versus continuous infusion of morphine during vaso-occlusive crisis in sickle cell disease, a randomized controlled trial. Am J Hematol. 2007;82(11):955-960. https://doi.org/10.1002/ajh.20944.

for a patient with recurrent vaso-occlusive crisis secondary to Sickle Cell Disease.

Early Closure Of Colostomy From Abdominal Trauma May Be Beneficial In Otherwise Healthy Patients, Nicole Xu

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising

Khalid MS, Moeen S, Khan AW, Arshad R, Khan AF. Same admission colostomy closure: a prospective, randomised study in selected patient groups. Surgeon. 2005;3(1):11-14. https://doi.org/10.1016/s1479-666x(05)80004-6

for a patient with loop transverse colostomy due to trauma

Evaluating The Use Of Cheaper, Less Effective Medications In Patients With Cost-Based Medication Nonadherence, Muneer F. Hasso

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Sangaralingham LR, Sangaralingham SJ, Shah ND, Yao X, Dunlay SM. Adoption of Sacubitril/Valsartan for the Management of Patients With Heart Failure. Circ Heart Fail. 2018;11(2):e004302. https://doi.org/10.1161/circheartfailure.117.004302

for a patient with low medication adherence rates due to the high out-of-pocket costs of newer medications.

Motivational Interviewing May Resolve Vaccine Hesitancy, Scott L. Baughan

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Gagneur A, Lemaître T, Gosselin V, et al. A postpartum vaccination promotion intervention using motivational interviewing techniques improves short-term vaccine coverage: PromoVac study. BMC public health. 2018;18(1):811. https://doi.org/10.1186/s12889-018-5724-y

for a juvenile patient with a caregiver who is skeptical about the safety of routine vaccinations.

Buprenorphine/Suboxone Is Safe In Pregnancy: Substance Use And Stigma In The Healthcare Professions, Blake S. Sanford

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Mullins N, Galvin SL, Ramage M, et al. Buprenorphine and Naloxone Versus Buprenorphine for Opioid Use Disorder in Pregnancy: A Cohort Study. J Addict Med. 2020;14(3):185-192. https://doi.org/10.1097/ADM.0000000000000562

for a woman with opioid use disorder during pregnancy.

Flexner Report 3.0—Structurally Competent Healthcare, James Peter Meza

Clinical Research in Practice: The Journal of Team Hippocrates

The editor advocates to formalize the addition of “Medical Social Sciences” as a basic science in our Schools of Medicine and “Clinical Decision Science” as the corollary clinical practice discipline: a “Flexner Report 3.0."

Editorial: Debates In Cardiovascular Pharmacology And Drug Discovery: 2022, Keman Xu, Fatma Saaoud, Ying Shao, Yifan Lu, Xiaohua Jiang, Sheng Wu, Jianxin Sun, Filipe Fernades Conti, Laisel Martinez, Roberto Vazquez-Padron, Hong Wang, Xiaofeng Yang

Center for Translational Medicine Faculty Papers

No abstract provided.

Novel Therapy Targeting Mutant-Krasg12d And Galectin-1 In Pancreatic Cancer, Ana I. Martinez Bulnes, Nirnoy Dan, Poornima Devi Shaji, Swathi Holla, Murali M. Yallapu, Sheema Khan

Research Colloquium

Introduction: Although, surgical resection and chemotherapy are the gold standard for treating Pancreatic Ductal Adenocarcinoma (PDAC), low patient survival rate remains the problem. The activating point mutation of the KRAS on codon-12 is present in 70–95% of PDAC cases and so far, no success has been achieved to inhibit KRAS. KRASG12D regulates cell proliferation, differentiation, apoptosis. Recent preliminary and published studies show high Galectin-1 (Gal-1) levels in both pancreatic cancer and stromal cells, which modulate tumor microenvironment and metastasis. Additionally, genetic deletion of gal1 inhibits metastasis and improves survival in KRAS mouse model of PDAC (1). Therefore, our objective is …

A Novel Approach To Target Tumor Immune Microenvironment And Improve Checkpoint Immunotherapies, Poornima Devi Shaji, Ana Martinez, Melida Flores Cantu, Anupam Dhasmana, Meena Jaggi, Stephen W. Behrman, Murali M. Yallapu, Subhash C. Chauhan, Sheema Khan

Research Colloquium

Background: Pancreatic cancer remains 3^rd deadliest disease, with less than 7-10% survival rate. Little progress has been seen in patient’s outcome due to high desmoplasia and chemo-resistance. Immunotherapy has shown promising results in cancers, except pancreatic cancer due to their characteristic fibrotic tumor microenvironment. The therapies are unable to penetrate fibrotic tumor leading to insufficient availability of therapeutic drugs at the tumor site. A recently identified mucin, MUC13 is aberrantly expressed in pancreatic tumors but not in normal pancreas, that makes it an excellent protein tumor target. This study is unique as it utilizes MUC13Ab for targeting the pancreatic …

Novel Therapy Targeting Mutant-Krasg12d And Galectin-1 In Pancreatic Cancer, Ana I. Martinez Bulnes, Poornima Devi Shaji, Swathi Holla, Nirnoy Dan, Shabnam Malik, Murali M. Yallapu, Meena Jaggi, Stephen W. Behrman, Subhash C. Chauhan, Sheema Khan

Research Colloquium

Introduction: In pancreatic ductal adenocarcinoma (PDAC), low patient survival rate remains a problem. The activating point mutation of KRAS on codon-12 is present in 70–95% of PDAC cases and so far, no success has been achieved to inhibit KRAS. KRAS^G12D regulates cell proliferation, differentiation, apoptosis; recent preliminary and published studies show high Galectin-1 (Gal-1) levels in both PDAC and stromal cells, which modulate tumor microenvironment and metastasis. Therefore, we have developed a novel combination therapy for PDAC by targeting mutated KRAS^G12D and Gal-1 to target both proliferation and metastasis in PDAC. This includes the delivery of KRAS^{G12D …}

Global Impact Of Proteoglycan Science On Human Diseases, Christopher Xie, Liliana Schaefer, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

In this comprehensive review, we will dissect the impact of research on proteoglycans focusing on recent developments involved in their synthesis, degradation, and interactions, while critically assessing their usefulness in various biological processes. The emerging roles of proteoglycans in global infections, specifically the SARS-CoV-2 pandemic, and their rising functions in regenerative medicine and biomaterial science have significantly affected our current view of proteoglycans and related compounds. The roles of proteoglycans in cancer biology and their potential use as a next-generation protein-based adjuvant therapy to combat cancer is also emerging as a constructive and potentially beneficial therapeutic strategy. We will discuss …

A Multi-Modal Imaging Analysis Of Inter-Community Hub Nodes In Subjective Cognitive Decline Linking Longitudinal Hub Function Disruption To White Matter Integrity Kurtosis, Duncan Nowling

MUSC Theses and Dissertations

Subjective Cognitive Decline (SCD) has garnered much interest as a potential identifiable preclinical stage and indicator of risk for cognitive decline in Alzheimer’s Disease and related dementias (ADRD). Identification of individuals in this stage though is difficult, as they present with objectively normal cognitive evaluation scores, relying instead upon self-report of concern about decline in cognitive abilities. The use of non-invasive in-vivo imaging methods like BOLD functional imaging and diffusion tensor have allowed for complex mapping of both the functional and structural network features unique to this condition. This study furthers this network biomarker map of SCD by investigating the …

Reclaiming The Balance: Blocking Glutamine Uptake To Restrain Pulmonary Fibrosis, Gang Liu, Ross Summer

Center for Translational Medicine Faculty Papers

No abstract provided.

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 …

Early Development Of C3ar1-Targeting Chimeric Antigen Receptor T Cells For The Treatment Of Glioblastoma Multiforme, Cameron Fraser

Electronic Theses, Projects, and Dissertations

Glioblastoma multiforme is the most aggressive type of glioma, demonstrating extremely low long-term survival despite modern therapies. Chimeric antigen receptor T cells have shown extreme levels of success in the treatment of B cell lymphomas through persistent anti-tumor activity. Prior research has demonstrated the therapeutic potential in targeting the C3a-C3aR1 pathway as it acts in an autocrine loop, maintaining the proliferation and survival of cancer stem cells within the tumor. Here, we reorient the treatment to target C3aR1 for the treatment of glioblastoma multiforme. In order to achieve this, Jurkat immortalized T cells will express various chimeric antigen receptor designs …