Pathology Commons^™

Disease-Causing Mfn2 Mutants Impair Mitochondrial Fission Dynamics By Distinct Drp1 Dysregulation, Daniel Lagos, Pamela R. De Santiago, Nicolás Pérez-Bravo, Benjamín Cartes-Saavedra, Josefa Vial-Brizzi, Diego Troncoso-Chandía, Oliver Podmanicky, Rita Horvath, Verónica Eisner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mitochondria undergo fusion and fission. While DRP1 regulates fission, fusion is controlled by OPA1, MFN1, and MFN2. The balance between these processes and the crosstalk between machineries remains poorly understood. MFN2 mutations cause Charcot-Marie-Tooth disease type 2 A (CMT2A), affecting mitochondrial fusion and morphology. However, their role in fission is unclear. Using skin fibroblasts from CMT2A patients (L248H and M376V MFN2 mutations) and wild-type mouse embryonic fibroblasts expressing these variants, we studied how MFN2 mutations impact mitochondrial dynamics beyond fusion. We analyzed mitochondrial morphology and dynamics by live-cell confocal microscopy and tested fusion/fission protein levels, oxygen consumption rate (OCR), extracellular …

Global Burden Of Drug-Resistant Tuberculosis In Children: A Systematic Analysis For The Global Burden Of Disease Study, Xuhui Liu, Peierdun Mijiti, Lu Xia, Sylvia M Lacourse, Wulan Talafuhan, Alexander W Kay, Yang Yang, Huarui Liu, Dan Ye, Leonardo Martinez, Shuihua Lu, Adong Shen, Anna M Mandalakas, Feng Li, Christoph Lange, Zhen Huang

Faculty, Staff and Students Publications

Background: Paediatric tuberculosis (TB), particularly drug-resistant TB (DR-TB), is associated with significant mortality. However, the global burden of childhood TB remains poorly understood.

Methods: We analysed incident cases, deaths, and age-standardised incidence and mortality rates among children (0-14 years) with multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) and extensively drug-resistant tuberculosis (XDR-TB) using the Global Burden of Disease (GBD) 2021 database. Data were stratified by age, sex, region, country, and HIV/AIDS status. Annual and average annual percentage changes were assessed using joinpoint regression analysis. Secondary analyses compared adult and paediatric TB trends in the End TB era and evaluated the potential impact of the …

Routine Transfusion Of Rh(D)-Positive Rbcs To Rh(D)-Negative Patients Designated As Do Not Resuscitate Conserves Rh(D)-Negative Red Blood Cell Inventory, Julie Katz Karp, Jovanna Everetts, Juliana Guarente, Angelica Vivero, Tiffany Bohr, Mary Harach

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: A minority of blood donors are Rh(D)-negative, and Rh(D)-negative red blood cell (RBC) products are often overutilized. As such, Rh(D)-negative RBCs may be difficult to maintain in blood bank inventory.

Study design and methods: We changed our blood bank laboratory policy to approve non-alloimmunized Rh(D)-negative patients to receive Rh(D)-positive RBCs for routine transfusion under defined criteria. Those criteria included Rh(D)-negative males (all ages) and females (aged >50 years) who were designated as do not resuscitate (DNR), either with or without intubation, in the electronic medical record.

Results: From August 15, 2024 through August 15, 2025, a total of 204 …

Hematochezia In A Patient With End-Stage Renal Disease, Brennan Gioe, Conrad Fernandes, E Celia Marginean, Stalin Subramanian

Faculty, Staff and Students Publications

No abstract provided.

Incidence And Risk Factors For Stillbirth In Kenya, Mozambique And The Gambia: The Precise Cohort Study, Grace Mwashigadi, Joseph Akuze, Angela Koech, Hawanatu Jah, Anna Roca, Geoffrey Omuse, Moses Mukhanya, Marleen Temmerman, Amina Abubakar, Patricia Okiro

Centre of Excellence in Women and Child Health

Background

Methods

Fda Approval Of Tradipitant: A Novel Approach To Motion Sickness Treatment, Haley Brown, Jennifer Cao, Allie Honigford, Leah Heitkamp, Sarah Hiett, Connor Dains, Brenna Hissong, Manoranjan D'Souza

Pharmacy and Wellness Review

Motion sickness is a prevalent neurophysiological condition affecting approximately one-third of the worldwide population, resulting from sensory mismatch and the brain’s internal model of motion. It is characterized by nausea, vomiting, dizziness, and autonomic symptoms during exposure to actual or virtual motion, which may significantly impair daily functioning and quality of life. Current guidelines recommend the prevention and treatment of motion sickness through pharmacologic, herbal, and non-pharmacologic strategies. Scopolamine and first-generation antihistamines are effective pharmacologic options, while ginger has demonstrated some benefit in reducing symptoms as an herbal option. Non-pharmacologic interventions such as habituation training, behavioral techniques, and sensory strategies …

Correction: Misregulated Alternative Splicing In Endometriosis: A Role For Aberrant Mrna Variants In Endometriotic Cell Growth, Venkata Naga Goutham Davuluri, Michelle Dias, Roxanna Llinas, Neha Kamath, Pooja Popli, Shannon M Hawkins, Chandrakant Tayade, Elise T Courtois, Hari Krishna Yalamanchili, Ramakrishna Kommagani

Faculty, Staff and Students Publications

This corrects the article "Misregulated alternative splicing in endometriosis: a role for aberrant mRNA variants in endometriotic cell growth", 149.

Development Of A Second-Generation Rarα Selective Antagonist As An Orally Bioavailable, Effective, Safe, And Reversible Male Contraceptive, Rui Shi, Kristen John, Xuan Qin, Ehfazul Haque, Taimeng Liang, Narsihmulu Cheryala, Feng Li, Henry L Wong, Gunda I Georg

Faculty, Staff and Students Publications

We report the design and SAR studies of benzopyran-, benzofuran-, and benzothiophene-derived inhibitors of the retinoic acid receptor alpha (RARα) for male contraception. SAR studies identified critical features influencing activity, such as the optimal positioning of antagonism moieties and substituents, leading to the discovery of (S)-4-(5-(2,8-dimethyl-5-(p-tolyl)-2H-chromen-3-yl)-1H-pyrrol-2-yl)­benzoic acid (compound 23). Compound 23 is a highly potent RARα inhibitor (IC50 = 0.051 nM) with excellent selectivity (>1650-fold over RARβ and >1960-fold over RARγ) and ADMET properties. Compound 23 is orally bioavailable and reduces sperm counts in mice for a full male contraceptive effect …

Progressive Cardiac Phenotypes And Reduced Reversibility From Long-Term Cugexp Rna Expression In A Dm1 Mouse Model, Rong-Chi Hu, Mohammadreza Tabary, Xander Ht Wehrens, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic dystrophy type 1 (DM1) is caused by an expanded CTG repeat in the DMPK gene, resulting in mutant transcripts that form expanded CUG (CUGexp) RNA foci and sequester muscleblind-like (MBNL) RNA-binding proteins. DM1 is multisystemic, with progressive worsening of disease manifestations in affected tissues. Disease progression is attributed to somatic expansion of the CTG repeats with age, resulting in production of CUGexp RNA with enhanced intrinsic toxicity due to increased MBNL sequestration. To determine the degree to which cardiac disease progression can occur independently of repeat expansion, we used a transgenic DM1 mouse model with inducible heart-specific expression of …

Fetal Vascular Malperfusion And Other Placental Lesions In Relation To Maternal Sars-Cov-2 Exposure: A Case–Control Study, Irene Mwandoto, Marleen Temmerman, Ingrid Gichere, Patricia Okiro

Pathology, East Africa

Background:

The morphologic characteristics of placentas associated with coronavirus disease-19 (COVID-19) have been described but with varying findings. Studies conducted at the onset of the pandemic reported frequency of Fetal Vascular Malperfusion (FVM), an umbrella term that describes occlusive vasculopathies that affect fetal circulation and their associated sequelae. Morphologic manifestations include thrombosis, avascular villi and vascular stromal karyorrhexis. Associated outcomes include fetal growth restriction, thromboembolic events such as neonatal stroke and fetal demise. Placental lesions associated with a severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection present a unique picture in histology, especially in the attempt to decipher the …

Validation Of A Real-Time Pcr Laboratory Developed Test For The Detection Of Pneumocystis Jirovecii In Bronchoalveolar Lavage Samples, Caitlyn Moon

Honors Scholar Theses

Pneumocystis jirovecii is an opportunistic, host-obligate fungal pathogen responsible for causing P. jirovecii pneumonia (PJP) in humans. PJP is treated with trimethoprim-sulfamethoxazole (TMP-SMX), a strong broad-spectrum antibiotic that carries risk of renal and hepatotoxicity. Therefore, rapid diagnosis or exclusion of PJP is crucial to ensure PJP-positive patients receive effective treatment and PJP-negative patients avoid unnecessary antibiotics. Unlike most microorganisms, P. jirovecii cannot be cultured, presenting complications for the typical methods of diagnosing fungal pathogens. Historically, the gold standard for diagnosis was direct microscopic examination with stains such as methenamine silver and calcofluor white, but this diagnostic technique requires highly skilled …

Low-Abundance And Fragmentary Helicobacter Pylori Dna Detected In Phenotypically Negative Gastric Biopsies Using Targeted Sequencing, Fabien Mbaya-Tshibangu, Alain Cimuanga-Mukanya, Evariste Tshibangu-Kabamba, Nadine Kayiba-Kalenda, Tressy Kalenga-Ngomba, Patrick Ngoma-Kisoko, Gunturu Revathi, Junko Akada, Benoît Mbiya-Mukinayi, Augustin Tshibaka Kabongo

Pathology, East Africa

Accurate detection and monitoring of antimicrobial resistance (AMR) in Helicobacter pylori mainly rely on phenotypic methods and culture, which can sometimes fail when bacterial load is low or after recent treatment. We investigated whether gastric biopsies classified as H. pylori-negative by standard diagnostic techniques still contain detectable bacterial DNA, including regions linked to AMR, and assessed whether selected DNA fragments can mediate allelic exchange in vitro. Gastric biopsies from 46 dyspeptic patients in the Democratic Republic of the Congo (including 23 phenotypically positive and 23 phenotypically negative individuals) were analyzed using long-read amplicon sequencing of seven resistance-associated loci, selective whole-genome …

Inhibition Of Cyclophilin D Rescues Cardiac Function And Bioenergetic Defects Caused By Neonatal Hypoxia, Jonathan R. Burris, Gisela Beutner, Min Yee, Bartholomew V. Simon, Michael F. Swartz, Kathryn B. Boudreau, Ethan D. Cohen, Chaitanya A. Kulkarni, Prottoy Hasan, Hongyue Wang, Karen L. De Mesy Bentley, György Hajnóczky, George M. Alfieris, Eric M. Small, Paul S. Brookes, Michael A. O'Reilly, George A. Porter

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Increased oxygen levels at birth regulate myocyte bioenergetic and structural maturation controlled by mitochondrial cyclophilin D (CypD). We evaluated mechanisms of neonatal hypoxic cardiac dysfunction by exposing neonatal mice to 12% oxygen and studied cardiac bioenergetics, myocyte maturation, and function. Hypoxia decreased the activity/assembly of electron transport chain complex I, uncoupled oxidative phosphorylation, increased proliferation, decreased differentiation, increased ventricular mass, and decreased cardiac function. CypD inhibition rescued most hypoxia-mediated effects and increased cardiac function. In conclusion, neonatal hypoxia alters cardiac bioenergetics, myocyte maturation, and cardiac function through CypD-dependent pathways, providing potential therapeutic targets for neonatal cardiac dysfunction.

Hydatid Cyst In The Right Ventricle Leading To Tricuspid Stenosis And Heart Failure: A Case Report, Muhammad Sheraz Hameed, Syed Rafay Hussain Zaidi, Shafaq Saleem, Muhammad Ahsan, Sarah Rahman, Azeen Razzaq, Ali Iqbal, Muhammad Sohaib Alvi, Muhammad Usama Naveed

Department of Medicine Faculty Papers

BACKGROUND: Cystic hydatid infection is a parasitic disease caused by the larval stages of Echinococcus granulosus, most commonly involving the liver and lungs. Cardiac involvement is rare, accounting for less than 2% of cases, with the left ventricle being the most commonly affected site. Involvement of the right ventricle is extremely uncommon and may lead to life-threatening complications such as tricuspid valve obstruction and hemodynamic compromise.

CASE PRESENTATION: We report a rare case of a 42-year-old patient who presented to the emergency department with exertional dyspnea, hemoptysis, chest pain, syncope, peripheral edema, and signs of right-sided heart failure. The patient …

A Rare Presentation Of Extra-Appendiceal Mucinous Neoplasm Of The Anus, Pincus Joshua, Marianne Estrada, Lance Horner University Of Nevada, Las Vegas

School of Medicine Research Poster Showcase

Introduction: Mucinous neoplasm of the anus is an uncommon malignancy, representing less than 3% of all anal cancers. Even more rare is extra-appendiceal mucinous neoplasm. As a result, limited literature exists to define diagnostic strategies and optimal management. Our case report details the presentation and management of a patient with recurrent mucinous neoplasm of the anus. Methods: A retrospective chart review was performed which includes clinic documentation., operative notes, pathology reports. Results: The patient is a 76-year-old male with a history of T3N0M0 anal mucinous carcinoma diagnosed in 2015 and treated with neoadjuvant chemoradiation with complete pathological response. In 2024, …

Ms-Gator: Multi-Scale Graph Attention With Topological Reasoning For Segmentation And Classification Of Prostate Cancer Based On Gleason Scores Using Histopathology Images, Sujata Patil, Mahadeva Swamy, Kavitha Sooda, Rajanikanth Vadigepalli, Khalid Nazim Abdul Sattar, Md Rafeeq

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Prostate cancer is one of the prevalent and potentially fatal malignancies, affecting men globally. Accurate segmentation and classification of prostate cancer in histopathology images remain challenging due to complex tissue architecture, staining variability, and high inter-observer differences in manual diagnosis. To address these challenges, this research proposes a Multi-Scale Graph Attention with Topological Reasoning (MS-GATOR) for segmentation and classification of prostate cancer based on Gleason Scores (GS). The MS-GATOR incorporates topological reasoning with hierarchical biological structures by constructing a graph-based representation among three spatial scales such as nuclei, glands, and tissues using Delaunay triangulation to capture both geometric and photometric …

Developing Endpoints For The Cardiac Burden In Myotonic Dystrophy Type 1: A Workshop Report, Julia M Hartman, Samuel Carrell, William J Groh, Thomas A Cooper, Jordana Kron, Greg Hundley, Jennifer Jordan, Amy Ladd, Man Hung, Nicholas E Johnson

Faculty, Staff and Students Publications

Cardiac disease is a well-established manifestation of myotonic dystrophy type 1 (DM1), characterized by progressive cardiac conduction slowing with increased risk of atrial and ventricular arrhythmias, heart block, and sudden cardiac death. Multiple disease modifying therapies are in clinical trials for DM1 and show promise in improving skeletal muscle weakness and myotonia. Testing the effects of these medicines, or others, in the heart is of critical importance, but requires identification of endpoints of cardiac function that accurately reflect the state of DM1 cardiac disease. To better define cardiac endpoints, the Myotonic Dystrophy Clinical Research Network (DMCRN) and the Myotonic Dystrophy …

Versatile Smad2 And Smad3 Epitope-Tagged Mouse Models For Genomic Profiling Of Tgfβ Signaling: Uncovering Gdf9-Smad2/3 Targets, Zian Liao, Qian Zhang, Keisuke Shimada, Kaori Nozawa, Suni Tang, Masahito Ikawa, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

Transforming growth factor β (TGFβ) signaling pathways are integral for a plethora of biological processes. SMAD2 and SMAD3 are the principal transcriptional effectors of TGFβ superfamily ligands, yet quantitative, genome-wide mapping of their DNA-associated complexes under physiological contexts has remained limited due to the lack of specific, robust models. Here, we generated two versatile epitope-tagged mouse models in which endogenous SMAD2 and SMAD3 proteins are globally tagged with hemagglutinin (HA) and podoplanin (PA) sequences, respectively, enabling high-fidelity profiling of SMAD2 and SMAD3 binding across tissues. To demonstrate the broad application of our models, we exemplified the usage of our lines …

Pseudo-Bartter Syndrome In A Pancreatic Insufficient Infant With Cftr, Dnah9, Lyst And G6pd Variants, Diana Marangu‐Boore, Doris Kinuthia, Janet Maranga, Peter Ngwatu, Joel Lessan, Rita Boateng

Pathology, East Africa

No abstract provided.

World Health Organization Classification Of Tumours Of The Breast 6th Edition 2026, Cecily Quinn, Puay Tan, Kimberly Allison, Edi Brogi, Sunil Lakhani, Stuart Schnitt, Stephen Fox, Shabnam Jaffer, Aysegul Sahin, Shahin Sayed

Pathology, East Africa

The 6th edition of the WHO Classification of Breast Tumours introduces both major and minor changes based on recent advances in our understanding of breast biology, developments in diagnostic modalities, identification of specific molecular targets and new treatment regimens necessitating modifications to pathology reporting and tumour biomarker categorisation. This review summarises the main changes that strive towards a classification of global relevance. In invasive carcinoma, predictive factors increasingly inform modern breast cancer treatment. The 6th edition provides an update on HER2 reporting categories following the DESTINY-Breast 04 and 06 trials. Terminologies used to classify invasive tumours are clarified, with the …