Medical Pathology Commons^™

Pi3k Isoform-Specific Regulation Of Leader And Follower Cell Function For Collective Migration And Proliferation In Response To Injury, Morgan D Basta, A. Menko, Janice L Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

To ensure proper wound healing it is important to elucidate the signaling cues that coordinate leader and follower cell behavior to promote collective migration and proliferation for wound healing in response to injury. Using an ex vivo post-cataract surgery wound healing model we investigated the role of class I phosphatidylinositol-3-kinase (PI3K) isoforms in this process. Our findings revealed a specific role for p110α signaling independent of Akt for promoting the collective migration and proliferation of the epithelium for wound closure. In addition, we found an important role for p110α signaling in orchestrating proper polarized cytoskeletal organization within both leader and …

Editorial: Epigenetics And Molecular Genetics Of Rare Tumors, Mauro Tognon, George A. Calin, Luis Del Valle

School of Medicine Faculty Publications

No abstract provided.

Bap1 Maintains Hif-Dependent Interferon Beta Induction To Suppress Tumor Growth In Clear Cell Renal Cell Carcinoma., Lauren Langbein, Rayan El Hajjar, Shen He, Eleonora Sementino, Zhijiu Zhong, Wei Jiang, Benjamin E Leiby, Li Li, Robert G Uzzo, Joseph R Testa, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BRCA1-associated protein 1 (BAP1) is a deubiquitinase that is mutated in 10-15% of clear cell renal cell carcinomas (ccRCC). Despite the association between BAP1 loss and poor clinical outcome, the critical tumor suppressor function(s) of BAP1 in ccRCC remains unclear. Previously, we found that hypoxia-inducible factor 2α (HIF2α) and BAP1 activate interferon-stimulated gene factor 3 (ISGF3), a transcription factor activated by type I interferons and a tumor suppressor in ccRCC xenograft models. Here, we aimed to determine the mechanism(s) through which HIF and BAP1 regulate ISGF3. We found that in ccRCC cells, loss of the von Hippel-Lindau tumor suppressor (VHL) …

Germline Polymorphisms In Mgmt Associated With Temozolomide-Related Myelotoxicity Risk In Patients With Glioblastoma Treated On Nrg Oncology/Rtog 0825, Michael E Scheurer, Renke Zhou, Mark R Gilbert, Melissa L Bondy, Erik P Sulman, Ying Yuan, Yanhong Liu, Elizabeth Vera, Merideth M Wendland, Emad F Youssef, Volker W Stieber, Ritsuko R Komaki, John C Flickinger, Lawrence C. Kenyon, H Ian Robins, Grant K Hunter, Ian R Crocker, Samuel T Chao, Stephanie L Pugh, Terri S Armstrong

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: We sought to identify clinical and genetic predictors of temozolomide-related myelotoxicity among patients receiving therapy for glioblastoma.

Methods: Patients (n = 591) receiving therapy on NRG Oncology/RTOG 0825 were included in the analysis. Cases were patients with severe myelotoxicity (grade 3 and higher leukopenia, neutropenia, and/or thrombocytopenia); controls were patients without such toxicity. A risk-prediction model was built and cross-validated by logistic regression using only clinical variables and extended using polymorphisms associated with myelotoxicity.

Results: 23% of patients developed myelotoxicity (n = 134). This toxicity was first reported during the concurrent phase of therapy for 56 patients; …

Proteômica Plasmática Quantitativa De Pacientes Sobreviventes E Não Sobreviventes De Covid-19 Internados No Hospital Revela Potenciais Biomarcadores Prognósticos E Alvos Terapêuticos, D C. Flora, A D. Valle, H Abs Pereira, T F. Garbieri, L. T. Grizzo, T J. Dionisio, A L. Leite, D Mc Rosa, C F. Santos, M Ar Buzalaf

Nebraska Center for Virology: Faculty Publications

O desenvolvimento de novas abordagens que permitam a avaliação precoce de quais casos de COVID-19 provavelmente se tornarão críticos e a descoberta de novos alvos terapêuticos são importantes. Neste estudo de coorte, foi avaliado o perfil proteômico e laboratorial do plasma de 163 pacientes internados no Hospital Estadual de Bauru (Bauru, SP, Brasil) entre 4 de maio e 4 de julho de 2020, que foram diagnosticados com COVID-19 por RT-PCR a partir de amostras de swab nasofaríngeo amostras. Amostras de plasma foram coletadas na admissão para análises laboratoriais de rotina e análise proteôomica quantitativa shotgun livre de marcadores. De acordo …

Diagnostic Accuracy Of High-Sensitivity Cardiac Troponin In The Diagnosis Of Acute Myocardial Infarction At The Aga Khan University Hospital Nairobi, Kenya, Assumpta Wanjiru Chege

Theses & Dissertations

Methodology: This cross-sectional study was carried out at Aga Khan University Hospital, Nairobi between July 1st 2020 and December 31st 2021. Participants were adults aged 18 years and above presenting to the emergency department with signs and symptoms suggesting an acute myocardial infarction. Patients were identified on the hospital management information system (CARE 2000) using test results for baseline high-sensitivity cardiac troponin I. The final diagnosis as well as secondary clinical data was obtained from both physical and electronic patient medical records. The reference standard for the diagnosis of acute myocardial infarction was taken as the final clinical diagnosis made …

Classification Of Breast Cancer Histopathological Images Using Semi-Supervised Gans, Balaji Avvaru, Nibhrat Lohia, Sowmya Mani, Vijayasrikanth Kaniti

SMU Data Science Review

Breast cancer is diagnosed more frequently than skin cancer in women in the United States. Most breast cancer cases are diagnosed in women, while children and men are less likely to develop the disease. Various tissues in the breast grow uncontrollably, resulting in breast cancer. Different treatments analyze microscopic histopathology images for diagnosis that help accurately detect cancer cells. Deep learning is one of the evolving techniques to classify images where accuracy depends on the volume and quality of labeled images. This study used various pre-trained models to train the histopathological images and analyze these models to create a new …

Associations Between Cannabis, Psychosis, And Schizophrenia In Adolescents, Lauren Moment

Academic Leadership Journal in Student Research

The effects of cannabis use on the brain, mind, and body have been studied for decades. The developing brain, particularly the adolescent and young adult brain, undergoes critical development that makes it especially susceptible to the effects of cannabis use. Among the adverse effects of cannabis use in adolescence and young adulthood, psychosis and psychotic disorders (e.g., schizophrenia) have been examined. The association of cannabis use with schizophrenia was first elucidated in a Swedish study of army conscripts. Specifically, conscripts reported their cannabis use exposure and were followed longitudinally to assess the emergence of schizophrenia. The authors found that those …

Unreliable Automated Complete Blood Count Results: Causes, Recognition, And Resolution, Gene Gulati, Guldeep Uppal, Jerald Z. Gong

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Automated hematology analyzers generate accurate complete blood counts (CBC) results on nearly all specimens. However, every laboratory encounters, at times, some specimens that yield no or inaccurate result(s) for one or more CBC parameters even when the analyzer is functioning properly and the manufacturer's instructions are followed to the letter. Inaccurate results, which may adversely affect patient care, are clinically unreliable and require the attention of laboratory professionals. Laboratory professionals must recognize unreliable results, determine the possible cause(s), and be acquainted with the ways to obtain reliable results on such specimens. We present a concise overview of the known causes …

Healthy Exosomes And Their Effects On Diabetic Cardiomyocytes, Miguel A. Garza, Genaro A. Ramírez-Correa, Maria Lourdes Garza-Rodríguez, Andres J. Medina

MEDI 9331 Scholarly Activities Clinical Years

Extracellular Vesicles, and more specifically, exosomes, are essential for effective cell-to-cell communication in a wide variety of tissues. In the last couple of decades, these nanovesicles have been proven to be active participants and regulators in many disease processes; therefore, their therapeutic effects have been widely studied and proven in various cardiovascular diseases both, in vitro and in vivo. Thus, this study aims at assessing the effects of running healthy mice exosomes on cardiomyocyte and cardiac tissue samples obtained from diabetic mice. Here, we successfully extract exosomes from mice plasma and detect their presence through the use of anti-CD9 and …

Steap1-4 (Six-Transmembrane Epithelial Antigen Of The Prostate 1-4) And Their Clinical Implications For Prostate Cancer, Michael Xu, Latese Evans, Candice L Bizzaro, Fabio Quaglia, Cecilia E Verrillo, Li Li, Julia Stieglmaier, M J Schiewer, Lucia R Languino, William Kevin Kelly

Department of Urology Faculty Papers

Six-Transmembrane Epithelial Antigen of the Prostate 1-4 (STEAP1-4) compose a family of metalloproteinases involved in iron and copper homeostasis and other cellular processes. Thus far, five homologs are known: STEAP1, STEAP1B, STEAP2, STEAP3, and STEAP4. In prostate cancer, STEAP1, STEAP2, and STEAP4 are overexpressed, while STEAP3 expression is downregulated. Although the metalloreductase activities of STEAP1-4 are well documented, their other biological functions are not. Furthermore, the properties and expression levels of STEAP heterotrimers, homotrimers, heterodimers, and homodimers are not well understood. Nevertheless, studies over the last few decades have provided sufficient impetus to investigate STEAP1-4 as potential biomarkers and therapeutic …

Patient With Multiple Genetically Distinct Thyroid Nodules Including Papillary Thyroid Carcinoma Harboring Novel Ywhag-Braf Fusion, Ruihe Lin, Zi-Xuan Wang, Elizabeth Cottrill, Nitika Badjatia, Stacey Gargano

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Next-generation sequencing (NGS) analysis of thyroid samples aids in risk stratification of cytologically indeterminate nodules and contributes to our understanding of molecular mechanisms in thyroid neoplasia. Several genes, including BRAF, RAS, and EIF1AX, are known to play a role in thyroid tumorigenesis. Here we report a case of papillary thyroid carcinoma (PTC) in which a single lesion harbored a novel YWHAG-BRAF fusion and EIF1AX mutation and displayed mixed morphological findings. The patient is a 74-year-old female with multiple incidentally discovered thyroid nodules, two of which were sampled by ultrasound-guided fine needle aspiration (FNA). Cytologic diagnosis for both nodules was suspicious …

Glucose Uptake By Glut1 In Photoreceptors Is Essential For Outer Segment Renewal And Rod Photoreceptor Survival, Lauren L. Daniele, John Y.S. Han, Ivy S Samuels, Ravikiran Komirisetty, Nikhil Mehta, Jessica L Mccord, Minzhong Yu, Yekai Wang, Kathleen Boesze-Battaglia, Brent A Bell, Jianhai Du, Neal S Peachey, Nancy J. Philp

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Photoreceptors consume glucose supplied by the choriocapillaris to support phototransduction and outer segment (OS) renewal. Reduced glucose supply underlies photoreceptor cell death in inherited retinal degeneration and age-related retinal disease. We have previously shown that restricting glucose transport into the outer retina by conditional deletion of Slc2a1 encoding GLUT1 resulted in photoreceptor loss and impaired OS renewal. However, retinal neurons, glia, and the retinal pigment epithelium play specialized, synergistic roles in metabolite supply and exchange, and the cell-specific map of glucose uptake and utilization in the retina is incomplete. In these studies, we conditionally deleted Slc2a1 in a pan-retinal or …

Altered Genome-Wide Hippocampal Gene Expression Profiles Following Early Life Lead Exposure And Their Potential For Reversal By Environmental Enrichment, Garima Singh, V Singh, T Kim, A Ertel, W Fu, J S Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Early life lead (Pb) exposure is detrimental to neurobehavioral development. The quality of the environment can modify negative influences from Pb exposure, impacting the developmental trajectory following Pb exposure. Little is known about the molecular underpinnings in the brain of the interaction between Pb and the quality of the environment. We examined relationships between early life Pb exposure and living in an enriched versus a non-enriched postnatal environment on genome-wide transcription profiles in hippocampus CA1. RNA-seq identified differences in the transcriptome of enriched vs. non-enriched Pb-exposed animals. Most of the gene expression changes associated with Pb exposure were reversed by …

Metastatic Primary Brain Rhabdomyosarcoma In A Pediatric Patient: Illustrative Case, Michel Gustavo Mondragón-Soto, Luis Del Valle, José Alfredo González-Soto, Roberto Alfonso De Leo-Vargas

School of Medicine Faculty Publications

BACKGROUND: Primary intracranial rhabdomyosarcoma is an extraordinarily rare malignant tumor, with even fewer presenting with distant metastasis. To date, only five cases, including the one presented here, have been reported to present metastatic activity. OBSERVATIONS: A 12-year-old boy presented with a few days of headache, nausea, vomiting, but no neurological deficit. Brain computed tomography and magnetic resonance imaging demonstrated hydrocephalus and a cystic lesion with left parieto-occipital extension. After resection, pathology reported primary rhabdomyosarcoma, with positive desmin and myogenin on immunohistochemistry. The patient presented with pulmonary metastasis. The patient had an overall survival of 21 months after diagnosis with optimal …

In Vivo Determination Of The Human Corneal Elastic Modulus Using Vibrational Optical Coherence Tomography, Marcos A. Crespo, Hiram J. Jimenez, Tanmay Deshmukh, Jose S. Pulido, Ahmed Saeed Saad, Frederick H Silver, Dominick A Benedetto, Christopher J Rapuano, Zeba Syed

Wills Eye Hospital Papers

Purpose: To determine the in vivo elastic modulus of the human cornea using vibrational optical coherence tomography (VOCT).

Methods: Vibrational analysis coupled with optical coherence tomography (OCT) was used to obtain the resonant frequency (RF) and elastic modulus of corneal structural components. VOCT corneal thickness values were measured using OCT images and correlated with corneal thickness determined with Pentacam (Oculus, Wetzlar, Germany). Moduli were obtained at two locations: central cornea (CC) and inferior cornea (IC). Measurements were obtained with and without anesthetic eye drops to assess their effect on the modulus measurements.

Results: VOCT thickness values correlated positively (R2 = …

Perioperative Risks Of The Patient With Heart Failure, Gabrielle Metoyer

Nursing Student Class Projects (Formerly MSN)

Perioperative Risks of the Patient with Heart Failure

Gabrielle Metoyer

Department of Nursing, Otterbein University

NURS 6810 – Advanced Pathophysiology

Dr. Deanna Batross and Dr. Shivani Bhatnagar

August 5, 2022

Abstract

According to the CDC (2020), heart failure occurs when the heart cannot pump enough blood and oxygen to support other organs in your body. Heart failure is an epidemic disease affecting 1-2% of the population worldwide (Schwinger, 2020). It is one of the leading causes of morbidity and mortality worldwide with an estimated 6.5 million adults with heart failure in the United States (Lo et al., 2021). Medical advances …

Whole Slide Image Data Utilization Informed By Digital Diagnosis Patterns, Kimberly Ashman, Huimin Zhuge, Erin Shanley, Sharon Fox, Shams Halat, Andrew Sholl, Brian Summa, J. Quincy Brown

School of Medicine Faculty Publications

Context: Despite the benefits of digital pathology, data storage and management of digital whole slide images introduces new logistical and infrastructure challenges to traditionally analog pathology labs. Aims: Our goal was to analyze pathologist slide diagnosis patterns to determine the minimum number of pixels required during the diagnosis. Methods: We developed a method of using pathologist viewing patterns to vary digital image resolution across virtual slides, which we call variable resolution images. An additional pathologist reviewed the variable resolution images to determine if diagnoses could still be rendered. Results: Across all slides, the pathologists rarely zoomed in to the full …

Sinus Pauses And Asystole As A Rare Presentation Of Thyrotoxic Crisis: A Case Report, Christian Akem Dimala, Charnjeet Sandhu, Oreoluwa Oladiran, Agnieszka Mochon, William Finneran Iii

Transformative Medicine (T-Med)

Introduction

Thyroid crisis is a rare and life-threatening endocrine emergency characterized by exaggerated clinical manifestations of hyperthyroidism with cardiovascular manifestations being the most severe. Rhythm disturbances, sinus tachycardia and atrial fibrillation, are the commonest cardiac manifestations of severe thyrotoxicosis; however, asystole remains a very atypical and uncommon presentation. We present a case of thyrotoxicosis due to Grave’s disease complicated by multiple episodes of asystole.

Case Presentation

A 65-year-old female recently diagnosed with Grave’s disease presented to the hospital with recurrent episodes of syncope. Her hospital course was significant for atrial fibrillation with subsequent progression to sinus pauses and asystole spontaneously …

A Mathematical Model Of Glut1 Modulation In Rods And Rpe And Its Differential Impact In Cell Metabolism, Andrea Aparicio, Erika T Camacho, Nancy J. Philp, Stephen A Wirkus

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

We present a mathematical model of key glucose metabolic pathways in two cells of the human retina: the rods and the retinal pigmented epithelium (RPE). Computational simulations of glucose transporter 1 (GLUT1) inhibition in the model accurately reproduce experimental data from conditional knockout mice and reveal that modification of GLUT1 expression levels of both cells differentially impacts their metabolism. We hypothesize that, under glucose scarcity, the RPE’s energy producing pathways are altered in order to preserve its functionality, impacting the photoreceptors’ outer segment renewal. On the other hand, when glucose is limited in the rods, aerobic glycolysis is preserved, which …