Medical Pathology Commons^™

Anti-Adamts13 Autoantibodies In Immune-Mediated Thrombotic Thrombocytopenic Purpura, Robert W. Maitta

Faculty Scholarship

Autoantibodies to ADAMTS13 are at the center of pathology of the immune-mediated thrombotic thrombocytopenic purpura. These autoantibodies can be either inhibitory (enzymatic function) or non-inhibitory, resulting in protein depletion. Under normal physiologic conditions, antibodies are generated in response to foreign antigens, which can include infectious agents; however, these antibodies may at times cross-react with self-epitopes. This is one of the possible mechanisms mediating formation of anti-ADAMTS13 autoantibodies. The process known as “antigenic mimicry” may be responsible for the development of these autoantibodies that recognize and bind cryptic epitopes in ADAMTS13, disrupting its enzymatic function over ultra large von Willebrand factor …

Long-Term Neurocognitive And Behavioral Outcomes In Survivors Of Pediatric Brain Tumors: A Systematic Review, Tori Sayers, Megan W. Szobody, Nina Mourao, Blake C. Martin, Sriya Gullapalli, Kory Punch, Tirath Patel, Murali Yallapu, Bharathi Shrikanth Gadad

Research Symposium

Background: Pediatric populations have an increased susceptibility for brain tumors and suffer from neurocognitive impairment due to the neoplasm itself, and side effect of subsequent treatments. This causes many patients to experience a subpar quality of life (QoL), affecting academic endeavors, social interaction and mental well-being. Increasing our understanding of the long-term effects associated with brain tumors and the side effects from our current treatment methodology will help us formulate better treatment protocols and improve survivors’ QoL. This review aims to investigate different long-term neurocognitive and behavioral outcomes in pediatric brain tumor survivors, as well as evaluate how various treatment …

Exploring The Mechanisms Of Varicella-Zoster Virus Pathogenesis And Its Potential Role In Oncogenesis, Fernando Cisneros, Blake Martin

Research Symposium

Background: Varicella-zoster virus (VZV) is a highly prevalent pathogen primarily recognized for causing chickenpox during primary infection and herpes zoster (HZ), also known as shingles, upon reactivation. While post-infectious complications of VZV, such as encephalitis, pneumonia, and post-herpetic neuralgia, are well-established, recent large population-based studies suggest that HZ may increase the risk of occult cancers. Emerging evidence suggests that VZV may modulate key oncogenic pathways, such as the inhibition of apoptosis, alteration of cell cycle regulatory enzymes, and interference with immunosurveillance, which could potentially promote cancer development. These findings indicate that VZV’s role in cancer biology may involve direct cellular …

Utilidad De La Combinación De Los Biomarcadores: Procalcitonina, Proteína C Reactiva Y Volumen Plaquetario Medio En El Diagnóstico Temprano De Sepsis Neonatal [Usefulness Of The Combination Of Biomarkers: Procalcitonin, C-Reactive Protein And Mean Platelet Volume In The Early Diagnosis Of Neonatal Sepsis], Oscar Manuel Berlanga Bolado Jr, Patricia Rivera Vazquez, Arely Socorro Hernández García, Angelica Lizbeth Martinez Ortiz

Research Symposium

Introducción: La sepsis neonatal es una causa frecuente de morbilidad y mortalidad infantil. Se le ha definido como un síndrome clínico caracterizado por signos sistémicos de infección, acompañado de bacteriemia en el primer mes de vida. Por lo tanto, el diagnóstico temprano es fundamental.

Objetivo: Conocer la sensibilidad y especificidad de la combinación de biomarcadores séricos como procalcitonina, proteína C reactiva y volumen plaquetario medio en el diagnóstico temprano de sepsis neonatal.

Material y métodos: Estudio clínico, de tipo prospectivo, predictivo, observacional, analítico, longitudinal y conveniencia. Se analizaron los biomarcadores como PCT, PCR, VPM para diagnosticar sepsis neonatal. Se incluyeron …

The Heterogeneity Of 13q Deletions In Chronic Lymphocytic Leukemia: Diagnostic Challenges And Clinical Implications, Changqing Xia, Guang Liu, Jinglan Liu, Arash Ronaghy, Saber Tadros, Wei Wang, Hong Fang, Shanxiang Zhang, Joseph D. Khoury, Zhenya Tang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia, particularly in Western countries. CLL can present indolently or aggressively, influenced by various factors, including chromosomal alterations. Fluorescent in situ hybridization (FISH), targeting specific genes/loci frequently affected in CLL patients, has established a standard for stratifying five CLL prognostic groups: del(11q)/ATM, trisomy 12, del(13q) as a sole aberration, del(17p)/TP53, and normal CLL FISH panel results. Among these, del(13q) as a sole aberration is associated with a favorable prognosis, while the others are considered intermediate (normal CLL FISH panel result and trisomy 12) or unfavorable (del(11q)/ATM and del(17p)/TP53) prognostic …

Thrombocytopenia In Sepsis, Alireza Setarehaseman, Robert W. Maitta

Faculty Scholarship

Platelets, traditionally known for their role in hemostasis, have emerged as key players in immune response and inflammation. Sepsis, a life-threatening condition characterized by systemic inflammation, often presents with thrombocytopenia, which at times, can be significant. Platelets contribute to the inflammatory response by interacting with leukocytes, endothelial cells, and the innate immune system. However, excessive platelet activation and consumption can lead to thrombocytopenia and exacerbate the severity of sepsis. Understanding the multifaceted roles of platelets in sepsis is crucial for developing effective therapeutic strategies. Targeting platelet-mediated inflammatory responses and promoting platelet production may offer potential avenues for improving outcomes in …

Effect Of Vitamin K Supplementation On Insulin Resistance: A Review, Samantha Mccord, Rebecca Willier, Kaitlyn Kirby, Kaylin Mahoney, Lance Dillon, Rileigh Rahrig, Brianna Lu, Joshua Honaker, Emily Eddy

Pharmacy and Wellness Review

Insulin resistance is one of the pathological hallmarks that leads to the development of type II diabetes mellitus (T2DM). Around 40% of people aged 18 to 44 living in the United States have insulin resistance. Recent research, coupled with a better understanding of how vitamin K functions in the body, suggests that this vitamin could potentially help reduce insulin resistance. Vitamin K is not included in the American Diabetes Association (ADA) guidelines for the treatment of insulin resistance, but it has been shown to have some benefits in patients with T2DM. It may also serve as a treatment option for …

Coronavirus Disease 2019 (Covid-19) Real World Data Infrastructure: A Big-Data Resource For Study Of The Impact Of Covid-19 In Patient Populations With Immunocompromising Conditions, James M. Crawford, Lynne Penberthy, Ligia A. Pinto, Keri N. Althoff, Magdalene M. Assimon, Oren Cohen, Laura Gillim, Tracy L. Hammonds, Shilpa Kapur, Harvey W. Kaufman, David Kwasny, Jean W. Liew, William A. Meyer 3rd, Shannon L. Reynolds, Cheryl B. Schleicher, Suki Subbiah, Catherine Theruviparampil, Zachary S. Wallace, Jeremy L. Warner, Suhyeon Yoon, Yonah C. Ziemba

School of Medicine Faculty Publications

Background. We developed a United States–based real-world data resource to better understand the continued impact of the coronavirus disease 2019 (COVID-19) pandemic on immunocompromised patients, who are typically underrepresented in prospective studies and clinical trials. Methods. The COVID-19 Real World Data infrastructure (CRWDi) was created by linking and harmonizing de-identified HealthVerity medical and pharmacy claims data from 1 December 2018 to 31 December 2023, with severe acute respiratory syndrome coronavirus 2 virologic and serologic laboratory data from major commercial laboratories and Northwell Health; COVID-19 vaccination data; and, for patients with cancer, 2010 to 2021 National Cancer Institute Surveillance, Epidemiology, and …

Alpha Synuclein And Inflammaging, Geneviève L. Putnam, Robert W. Maitta

Faculty Scholarship

The α-synuclein protein is an established molecule in Lewy body pathology, especially Parkinson's disease (PD). While the pathological role of α-synuclein (α-syn) in PD has been well described, novel evidence may suggest that α-syn interacts with inflammasomes in response to aging. As age is an inevitable physiological state and is also considered the greatest risk factor for PD, this calls for investigation into how α-syn, aging, and PD could be linked. There is a growing amount of data regarding α-syn normal function in the body that includes involvement in cellular transport such as protein complexes assembly, vesicular trafficking, neurotransmitter release, …

Mechanisms Of Familial And Uv-Induced Melanoma, Jeri D. Hughes

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Melanoma is the most common form of skin cancer in the United States. Melanoma is a disease where cancerous cells derive from melanocytes. Common melanoma susceptibility genes induce dysregulation in the mitogen-activated protein kinase (MAPK) pathway, phosphatase and tensin homolog (PTEN),and AKT expression. Melanoma can be induced through prolonged UV-radiation or familial diagnosis. This article aims to discuss the mechanisms of both familial and UV-induced melanomagenesis

Microrna 133a Regulates Squalene Epoxidase Expression In Colorectal Cancer Cells To Control Cell Proliferation And Cholesterol Production, Ji Su Mo, Santosh Lamichhane, Grinsun Sharma, Soo Cheon Chae

School of Medicine Faculty Publications

Background/Objectives: Colorectal cancer (CRC) is one of the most common cancers worldwide, with high incidence and mortality rates. MicroRNAs are endogenous and non-coding RNAs that play a pivotal role in the development and progression of various cancers by targeting specific genes. Previously, we identified MIR133A to be significantly decreased in human CRC tissues. This study aims to identify the relationship with SQLE, one of the candidate target genes of MIR133A, and study their interaction in CRC cells. Methods: Through the luciferase reporter assay, quantitative RT-PCR (qRT-PCR), and Western blot analysis. Results: We identified SQLE as a direct target gene of …

A Case Report Of Moderate Factor X Deficiency, Harpreet Kaur, Tanmoy Das, Poonam Wade, Murtuja Shaikh

Digital Journal of Clinical Medicine

Factor X deficiency is a rare coagulation disorder with a varied clinical spectrum. It can present at any age, but most severe cases present in childhood. There are no evidence-based management guidelines for the management of factor X deficiency due to limited literature. Detailed history, clinical examination and specialized tests (coagulation profile, mixing studies, factor assay) are required for the diagnosis of factor X deficiency. In this case report, we are discussing the case of a 1-month-old, 12-day-old female child who presented with the complaint of spontaneous bleeding from the nose since 1 day with no other bleeding manifestations from …

Rapid Neurological Decline Due To Creutzfeldt-Jakob Disease, Nicole Tesoro, David Blackwood, Robert Reif, Samuel Miller, Kalyan Paudel, Christopher Haas

Journal of Community Hospital Internal Medicine Perspectives

Creutzfeldt-Jakob Disease (CJD) is an exceedingly rare condition with an incidence of one case per million people worldwide. It is diagnosed with symptoms of rapid neurological decline, positive CSF biomarkers, and diagnostic findings on MRI and EEG. There is no known effective therapy for CJD and prompt diagnosis is required to prepare for the expected disease prognosis and goals of care discussions.

Pivotal Roles Of Biglycan And Decorin In Regulating Bone Mass, Water Retention, And Bone Toughness, Rui Hua, Yan Han, Qingwen Ni, Roberto J. Fajardo, Renato V. Iozzo, Rafay Ahmed, Jeffry S. Nyman, Xiaodu Wang, Jean X. Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Proteoglycans, key components of non-collagenous proteins in the bone matrix, attract water through their negatively charged glycosaminoglycan chains. Among these proteoglycans, biglycan (Bgn) and decorin (Dcn) are major subtypes, yet their distinct roles in bone remain largely elusive. In this study, we utilized single knockout (KO) mouse models and successfully generated double KO (dKO) models despite challenges with low yield. Bgn deficiency, but not Dcn deficiency, decreased trabecular bone mass, with more pronounced bone loss in dKO mice. Low-field nuclear magnetic resonance measurements showed a marked decrease in bound water among all KO groups, especially in Bgn KO and dKO …

An In Vivo Study Of Lns8801, A Gper Agonist, In A Spontaneous Melanoma-Prone Mouse Model, Tgs., Christina Marinaro, John Sauer, Christopher A Natale, Todd Ridky, Suzie Chen

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Melanoma is the most aggressive and deadly form of skin cancer that arises from the transformation of melanocytes, the pigment producing cells of the skin. In the year 2024 there will be approximately 10,000 new cases of melanoma diagnosed and approximately 8,000 deaths attributed to melanoma in the United States. In this study we treated a group of male and female transgenic mice that spontaneously develop metastatic melanoma, TGS, with a G-protein-coupled estrogen receptor agonist LNS8801 to assess the efficacy on disease progression. A second group of male and female TGS mice was also exposed to UVB irradiation to mimic …

Resilience And Reality: Exploring The Lived Experiences Of People Living With Hiv In Texas During The Covid-19 Pandemic – A Qualitative Study., Ahmed F. Alanazi

Social Work Dissertations - Archive

This study investigated the lived experiences of individuals living with HIV (PLWH) in the Dallas-Fort Worth (DFW) area of Texas during the COVID-19 pandemic, using an Interpretative Phenomenological Analysis (IPA) framework. The research examined the intersection of health, social dynamics, and psychological resilience among PLWH, who faced compounded vulnerabilities due to systemic inequities and the dual public health crises of HIV and COVID-19. Through semi-structured interviews with ten participants from diverse backgrounds, the study captured the profound impacts of disrupted healthcare systems, heightened stigma, and social isolation on this marginalized population. The findings reveal that the pandemic exacerbated existing inequities …

An Analytical Model Of Motion Artifacts In A Measured Arterial Pulse Signal—Part I: Accelerometers And Ppg Sensors, Md Mahfuzur Rahman, Subodh Toraskar, Mamun Hasan, Zhili Hao

Mechanical & Aerospace Engineering Faculty Publications

This paper, the first of two parts, presents an analytical model of motion artifacts (MAs) in measured pulse signals by accelerometers and photoplethysmography (PPG) sensors. As the transmission path from the true pulse signal in an artery to the sensor output (measured pulse signal), the tissue-contact-sensor (TCS) stack is modeled as a 1DOF (degree-of-freedom) system. MAs cause baseline drift of the mass and simultaneously time-varying system parameters (TVSPs) of the TCS stack. With arterial wall displacement and pulsatile pressure serving separately as the true pulse signal, an analytical model is developed to mathematically relate baseline drift and TVSP to a …

Coronary Artery Disease – Future Tools For Optimizing Primary Prevention, Nick Makosiej

Capstone Showcase

Coronary artery disease (CAD) is a progressive, obstructive, and inflammatory process affecting the endothelial lining of the coronary arteries, which ultimately compromises the perfusion of the myocardium and can lead to ischemic infarction. This narrowing of vasculature which supplies the myocardial tissue leads to a spectrum of anginal syndromes and inevitably, catastrophic consequences. This article is focused on understanding the pathophysiology of this disease process and educating providers on emerging clinical tools that can be utilized to prevent progression, and ultimately reduce morbidity and mortality of this insidious disease process.

Clinical Significance Of "S" Isoform Of Dclk1 In Different Gastric Cancer Subtypes Using Newly Produced Monoclonal Antibody, Mahdieh Razmi, Ali-Ahmad Bayat, Nafiseh Mortazavi, Elham Kalantari, Leili Saeednejad Zanjani, Sima Saki, Roya Ghods, Zahra Madjd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

Materials and methods

A Novel D-Peptide Modulates Dclk1 Gelsolin Interactions, Reducing Pdac Tumor Growth, Landon L. Moore, Dongfeng Qu, Parthasarathy Chandrekesan, Kamille Pitts, Randal May, Byron E. Anderson, Milton L. Brown, Courtney W. Houchen

Department of Medicine Faculty Publications

What drives inflammation-associated tumorigenesis and progression in pancreatic ductal adenocarcinoma (PDAC)? Doublecortin-like kinase 1 (DCLK1) is a central driver of inflammation-associated tumorigenesis, with elevated expression linked to worse clinical outcomes. Two isoforms of DCLK1 possess a unique extracellular domain (ECD). DCLK1 isoform 2 contains two microtubule-binding domains, while isoform 4, lacks the microtubule-binding domains but, plays a pivotal role in tumor progression. We identified novel D-peptides that selectively target this ECD, significantly suppressing PDAC cell proliferation in vitro and tumor growth in xenograft models without inducing cell death. In silico modeling and binding assays revealed DCLK1 isoform 4 interacts with …