Medical Pathology Commons^™

Stat4-Dependent Regulation Of Neuroinflammation In Atherosclerosis, Natalie Stahr, Alina K. Moriarty, Shelby D. Ma, W. Coles Keeter, Woong-Ki Kim, Larry D. Sanford, Elena V. Galkina

Department of Biomedical and Translational Sciences Faculty Publications

Atherosclerosis is linked to an increased risk of cognitive decline, with chronic inflammation being a common feature of both pathologies. IL-12 activates STAT4 to regulate myeloid cell functions, and blockade of this pathway alleviates cognitive impairment in Alzheimer's models. However, the mechanisms connecting vascular pathology to neuroinflammation remain unclear. Here, we examine whether STAT4 functions as a common mediator of neuroinflammation in atherosclerosis. We demonstrate that LysM^Cre-specific STAT4 deficiency ameliorates deficits in long-term memory in low-density lipoprotein-deficient (Ldlr^-/-) mice fed a high-fat diet (HFD-C). STAT4 deficiency moderately reduces Ser199-phosphorylated Tau burden. Atherosclerosis alters brain immune …

Educational Case: Atypical Presentation Of Primary Hyperparathyroidism With Brown Tumor, Ariel Flotte, Jonathan Light, Harrison Klause, Richard M. Conran

Department of Biomedical and Translational Sciences Faculty Publications

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology.

Inhibition Of Histone Demethylase Lsd1 Suppresses Cd47 Expression And Enhances Efficacy Of Cd47 Blockade In Breast Cancer, Fengjie Jiang, Yu Shen, Bing Li, Michael Henry, Nancy Davidson, Yi Huang

Department of Biomedical and Translational Sciences Faculty Publications

Background CD47 functions as a “don’t eat me” checkpoint, inhibiting macrophage-mediated phagocytosis in triple-negative breast cancer (TNBC). While anti-CD47 therapies can restore immune surveillance, their efficacy in TNBC is often limited by immune evasion and drug development challenges.

Methods We investigated the crosstalk between the histone demethylase lysine-specific demethylase 1 (LSD1) and CD47 signaling in TNBC using in silico datasets, isogenic cell lines, conditional BRCA1 knockout models, and syngeneic mouse models. Techniques such as immunohistochemistry, multiplex immunofluorescence, immunoprecipitation, protein ubiquitination, chromatin immunoprecipitation, chemotaxis, flow cytometry, and phagocytosis assays were employed to examine the epigenetic regulation of CD47 by LSD1 and …

Lipid And Foam Cell Accumulation As Novel Pathological Features Of Benign Prostatic Hyperplasia, Dita Julianingsih, Samara V. Silver, Thaissa Horne, Kasun Gunawardena, Savannah Ward, Alicia Malewska, Douglas Strand, Julius Nyalwidhe, Ilya Sobol, Petra Popovics

Department of Biomedical and Translational Sciences Faculty Publications

Background

Benign prostatic hyperplasia (BPH) encompasses a heterogeneous set of pathological processes that instigate lower urinary tract symptoms (LUTS). Using a mouse model of steroid hormone imbalance-induced lower urinary tract dysfunction, we identified luminal lipid-laden foamy macrophages, although their presence and contribution to human pathology have not yet been established. The objective of this study was to determine whether luminal macrophages are associated with human BPH and to assess how lipid accumulation relates to underlying pathological features and clinical parameters.

Methods

Whole-mount tissue sections from simple prostatectomy specimens and prostates from healthy donors were used to evaluate the association of …

Revised Microbiology Core Knowledge Objectives For Modern Undergraduate Medical Education, Timothy J. Bauler, Cindy G. Arvidson, Samina Akbar, Dennis N. Arvidson, Margaret E. Bauer, Dwayne M. Baxa, Rebecca J. Greenblatt, Kerstin Honer Zu Bentrup, Yingguang Liu, Inaia Phoenix, Julie A. Kerry

Department of Biomedical and Translational Sciences Faculty Publications

Defining the core content for each scientific discipline in a modern preclinical medical education curriculum is critical to ensure optimal student learning and application of foundational knowledge for clinical practice. Attendees of the Association of Medical School Microbiology and Immunology Chairs (AMSMIC) Educational Strategies Workshop recently highlighted the need for updated medical microbiology learning objectives, given the shift in medical education toward less time for preclinical coursework and more integrated learning. Herein, we describe the process of developing a comprehensive, educator-driven set of knowledge objectives for medical microbiology. These objectives emphasize common pathogens, as well as pathogens associated with severe …

Oropharyngeal Syphilis Presenting As Tongue Based Ulcer With Lymphadenopathy, Serena F. Pu, Kevin J. Carlson, Jonathan R. Mark, Benjamin J. Rubinstein

Department of Otolaryngology (ENT) Faculty Publications

Within the aerodigestive tract, syphilis presents with varied signs and symptoms, some of which may mimic malignancy or other disease processes. We present the case of a 29-year-old man with otalgia and odynophagia who was found on physical examination and office laryngoscopy to have a 4-cm ulcerative mass of the tongue base and cervical lymphadenopathy. While planning for tissue diagnosis, the patient’s serologies revealed positive treponemal antibody testing and elevated rapid plasma reagin (RPR) titers, confirming syphilitic infection, likely representing secondary syphilis. While awaiting operative biopsy, the patient received intramuscular penicillin with complete resolution of the mass and symptoms, and …

Assessment Of Skin In Patients With Systematic Sclerosis Using High-Frequency Ultrasound And Shear Wave Elastography: A Comparative Study With Histology, Molecular, And Clinical Parameters, Ruhani Desai, Filemon Tan, Minghua Wu, Jeffery L. Browning, Samuel Theodore, Meng Zhang, Brian Skaug, Harshdeep Singh Chawla, Manmohan Singh, Salavat Aglyamov, Kirill V. Larin, Maureen Mayes, Shervin Assassi

Department of Medicine Faculty Publications

Objective: Ultrasound (US) has been proposed as a potential tool for assessing skin fibrosis in systemic sclerosis (SSc). However, a large-scale comparison of US-based assessment with histologic markers of skin fibrosis has not been reported. We evaluated US-based skin assessments for their face validity (differentiation between involved SSc and healthy control [HC] skin), construct validity (comparison to modified Rodnan skin score [mRSS]), and criterion validity (comparison to histologic and gene expression fibrosis markers).

Methods: Twenty HCs and 52 patients with SSc underwent clinical and US assessment followed by a forearm skin biopsy. Predefined areas were assessed on the finger, hand, …

Cold-Sensitive Acral Hand Lesions, Avery H. Seward, Jocelyn H. Larocque

Department of Medicine Faculty Publications

[Case description] An otherwise healthy woman in her 60s presented with a 2-year history of a persistent, itchy, and tender rash on the dorsal hands. The rash fluctuated in severity with the seasons, worsening during the colder months. The patient denied joint pain and fatigue, or lesions elsewhere.

Examination revealed partially blanchable violaceous plaques on the dorsal hands with partial sparing of the proximal and distal interphalangeal joints (Fig 1). A few punctate, crusted erosions and purpuric macules were present on the dorsal and volar distal phalanges (Figs 2 and 3).

Consensus And Controversies Of International Guidelines For The Diagnosis, Surveillance, And Management Of Fetal Growth Restriction: An Updated Comparison, Daniele Diane Mascio, Suneet P. Chauhan, Tullio Ghi, Asma Khalil, Juliana G. Martins, Sara Sorrenti, Tamara Stampalija, Fabrizio Zullo, Francesc Figueras

Department of Obstetrics & Gynecology Faculty Publications

OBJECTIVE: To compare areas of consensus and disagreements across contemporary international and national guidelines on the diagnosis, surveillance, and management of fetal growth restriction (FGR).

DATA SOURCES: Electronic searches of MEDLINE from database inception up to March 2026 using MeSH terms and keywords related to FGR and guidelines. STUDY ELIGIBILITY CRITERIA: Critical, structured comparison of national or international guidelines on FGR published since 2010. Final inclusion required unanimous agreement from all authors.

STUDY APPRAISAL AND SYNTHESIS METHODS: Pre-specified extraction across domains: definition; prediction/prevention; surveillance tools and frequency; delivery timing and mode; and labor induction methods. Dual data …

Educational Case: Meningioma, Ashley M. Carter, Harrison Dai, Harrison Klause, Alberto Musto, Richard M. Conran

Department of Medicine Faculty Publications

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology.

Comparison Of Fully Covered Self-Expandable Metal Biliary Stents With Or Without Anchoring Double-Pigtail Plastic Stents: A Systematic Review And Meta-Analysis, Samuel Tanner, Fadi Hawa, Alejandra Vargas, Priyata Dutta, Antonio Facciorusso, Jean M. Chalhoub, Jorge D. Machicado

Department of Medicine Faculty Publications

Background and AIMS

Fully covered self-expandable metal stents (FcSEMSs) have become the mainstay of treatment for a variety of biliary pathologies. However, FcSEMSs have been associated with a greater rate of stent migration than other types of stents. A technique of anchoring double-pigtail plastic stents (DPPSs) has been proposed to minimize migration of biliary FcSEMSs. Herein, we evaluated the efficacy of anchoring DPPSs among patients treated with biliary FcSEMSs.

Methods

We performed a systematic review using PubMed, EMBASE, and Web of Science from database inception through August 2023. Full-text articles comparing FcSEMSs with or without anchoring DPPSs were included. We …

Paneugenesis: A Regenerative Systems Hypothesis For Advancing Health Promotion, Craig M. Becker, Leslie Hoglund, Beth Chaney, Joseph G. L. Lee, Michael Stellefson, Alex Davis

Epidemiology, Biostatistics, & Environmental Health Faculty Publications

Despite major advances in health promotion science, dominant approaches remain largely prevention-and risk-reduction-oriented. The prevailing orientation creates a substantial opportunity to advance generative, system-design strategies that intentionally produce well-being rather than merely prevent disease. This article proposes paneugenesis as a regenerative systems framework and a testable theoretical model for the intentional creation of net-positive outcomes, thereby extending health promotion beyond its traditional pathogenic emphasis. Paneugenesis integrates systems science, salutogenesis, behavioral science, complexity theory, and quality management principles into a unified four-function process: operationalizing idealized outcomes, identifying key precursors, optimizing processes, and continually plotting progress through feedback mechanisms. The central hypothesis …

Using Atrial Pacing Trials After Tavr To Assess Conduction Abnormalities And Predict Need For Pacemaker Implantation, Hemish M. Philip, Matthew R. Summers, Shirish R. Yasa, Hasani Amir, Daiwik P. Munjwani, Thomas A. Cook, Matthew G. Jackson

Cardiovascular Research Symposium

Abstract:

Background: Transcatheter Aortic Valve Replacement (TAVR) is the standard of care for many patients with severe aortic stenosis who cannot undergo surgical intervention. However, conduction disturbances remain a frequent complication, particularly with self-expanding valves. This often leads to permanent pacemaker implantation (PPI). At Sentara Heart Hospital, atrial pacing at 140 bpm is standard practice during TAVR to assess AV conduction.

Objective: This study aims to evaluate whether preserved 1:1 atrioventricular (AV) conduction during routine atrial pacing at 140 bpm after self-expanding TAVR predicts a low likelihood of requiring PPI, thus yielding a high negative predictive value (NPV).

Methods: We …

Development Of Overt Hypo-Attenuated Leaflet Thickening Following Transcatheter Aortic Valve Replacement, Stephonda Lewis, Hemish M. Philip, Matthew Summers

Cardiovascular Research Symposium

Background: Transcatheter aortic valve replacement (TAVR) is a cornerstone therapy for severe aortic stenosis. Up to one-third of patients develop hypoattenuated leaflet thickening (HALT) within the first year post-TAVR. HALT, a form of leaflet thrombosis, can progress to leaflet immobility and structural deterioration. Despite its significance, no unified approach exists for screening or management of HALT after TAVR.

Case Presentation: A 64-year-old woman presented with shortness of breath on exertion. Exam revealed a 3/6 systolic murmur, and echocardiogram confirmed severe aortic stenosis. She underwent TAVR with resolution of symptoms and was discharged on clopidogrel (Plavix) as single antiplatelet therapy. Two …

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 …

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 …

Socioeconomic Status And Health Disparities Drive Differences In Accelerometer-Derived Physical Activity In Fatty Liver Disease And Significant Fibrosis, Lucia Tabacu, Sajag Swami, Mark Ledbetter, Mohamad S. Siddiqui, Ekaterina Smirnova

Mathematics & Statistics Faculty Publications

Background and aims

The cornerstone of clinical management of patients with nonalcoholic fatty liver disease (NAFLD) are lifestyle changes such as increasing physical activity (PA) aimed at improving cardiometabolic risk. To inform NAFLD prevention and treatment guidelines we aimed to: (i) quantify the role of PA on lowering the risk for NAFLD and fibrosis; (ii) characterize NAFLD and fibrosis association with PA in the context of socioeconomic environment.

Methods

A sample of 2648 participants from the NHANES 2003–2006 was selected to develop survey weighted multivariable logistic regression models for predicting NAFLD and significant fibrosis, diagnosed non-invasively via fatty liver index …

Extending The Gift—Utilizing Residual Human Anatomical Materials For Training Pathologists' Assistants In Surgical Pathology Techniques, Kerwin M. Kolheffer, Lauren Yoho, Matthew Myers, Ismail El Moudden

Department of Pathology & Anatomy Faculty Publications

This study investigates the effectiveness of using residual human anatomical materials, obtained from a gross anatomy course, for training Pathologists' Assistant (PathA) students in surgical pathology techniques. We utilized two surveys to assess the perceived efficacy of this approach: one survey targeted PathA students to evaluate their training experiences with both human and animal tissues, while the other assessed the impact of specimen collection on the educational experiences of gross anatomy course students.

Determination Of Pancreatic And Salivary Amylase By Enzyme Immunoassay And Their Prevalence In Hyperamylasemic Patients, Sabdra Borgens Ward

Theses and Dissertations in Biomedical Sciences

Currently, amylase determinations are nonspecific for the organ source and are based entirely on the enzymatic properties of amylase to produce a measurable product or byproduct. The determination of pancreatic amylase is important in the diagnosis of acute pancreatitis. Most commercially available tests for amylase employ the measurement of the change in NADH absorbance at 280 nm or of the p-nitrophenol released from a maltotetrose substrate. These are nonspecific measurements of pancreatic amylase and often necessitate other tests to be run such as a serum lipase.

The two predominant isoenzymes of amylase are pancreatic (p-amylase) and salivary (s-amylase); the most …

A Batch Method For The Isolation Of Immunogenically Pure Igg, Iga, And Igm From Human Sera, Samuel Christopher Powell

Chemistry & Biochemistry Theses & Dissertations

A method is described for preparing an enriched fraction of the three major antibodies, immunoglobulins IgG, IgA and IgM, from normal human serum by a batch method. Selective precipitation of these proteins was carried out in successive steps using polyethylene glycol (PEG) of average molecular weight 6,000 at concentrations of 7%, 12% and 14% (16) . Zinc sulfate (10 mM) was used to remove highly immunogenic alpha₂ macroglobulin from the IgM fraction. IgA, IgM and IgG were further purified by adsorption methods using DEAE-cellulose. Quantitation and qualitation of the enriched fractions showed nearly complete separation of each of the …