Digital Commons Network^™

Mic60/Mitofilin Inhibitor, Miclxin, Induces Rat H9c2 Cardiomyoblast Death By Inhibiting The Removal Of Damaged Mitochondria, Muhammad S Khan, Somayyeh Nasiripour, Michele Oyarzabal, Swati Banerjee, Kumar Sharma, Manzoor A Bhat, Jean C Bopassa

Faculty, Staff and Student Publications

Mitochondrial dysfunction is a hallmark of various pathologic conditions, including ischemia/reperfusion injury, stroke, myocardial infarction, neurodegeneration and metabolic syndrome. As with all biological organelles, the function of mitochondria is tightly linked to their structure. The inner mitochondrial membrane is a highly regulated membrane with a large surface area that hosts the electron transport chain machinery, generates the membrane potential necessary for ATP generation, and forms the signature cristae folds of mitochondria. The mitochondrial inner membrane protein (Mitofilin/Mic60) is part of a large complex that constitutes the mitochondrial inner membrane organizing system, which is critical in maintaining mitochondrial architecture and function. …

Prenatal Alcohol Exposure Inhibits Transient Expression Of Autophagy And Synaptic Proteins In Developing Brain, Monica Hampe, Nune Darbinian, Nana Merabova, Armine Darbinyan, Jamal Hamze, Uday Bharai, Yuri Persidsky, Mary F Morrison, Shohreh Amini, Laura Goetzl, Michael E Selzer

Faculty, Staff and Student Publications

Introduction: Neuronal apoptosis and consequent inhibition of autophagy, with loss of synaptic connections are central events in the genesis of fetal alcohol spectrum disorders (FASD). However, studies of molecular mechanisms of autophagy in human fetal brain are limited. Recently, prenatal exposure to EtOH was associated with reduced miRNA-9 levels in fetal brain-derived exosomes (FB- Es) isolated from maternal plasma, which correlated with small eyes, an anatomical hallmark of fetal alcohol syndrome (FAS). Since miR-9 targets several genes that regulate synaptic plasticity, EtOH-induced inhibition of miR-9 could potentially result in dysregulation of genes involved in synaptogenesis/plasticity.

Methods: Rats were fed a …

Case Report: Rare Intraventricular H3 K27-Altered Diffuse Midline Glioma In An Adult, Merari Jasso, Jay-Jiguang Zhu, Meenakshi B Bhattacharjee, Georgene W Hergenroeder

Faculty, Staff and Student Publications

H3 K27-Altered Diffuse Midline Gliomas are commonly found in children and adolescents in midline locations such as the thalamus, brain stem, and spinal cord. It is rare for these tumors to affect adults and to occur in locations like the lateral ventricles. Despite aggressive treatment methodologies, there is no cure for this disease. The median survival is between 8-12 months. A 24-year-old white male presented to the emergency department due to severe headache refractory to pain medications with a 2-month history of progressive headaches and eventual memory problems. Computed tomography (CT) and magnetic resonance imaging (MRI) showed an intraventricular enhancing …

Re-Stenting Following Recurrence After Successful Venous Sinus Stenosis Stenting For Idiopathic Intracranial Hypertension, Salvatore A D'Amato, Juan Carlos Martinez Gutierrez, Hussein A Zeineddine, Eric Claude Mohan, Tien Nguyen, Cybele Woon, Rosa Tang, Peng Roc Chen

Faculty, Staff and Student Publications

Objective: In medically refractory idiopathic intracranial hypertension (IIH), venous sinus stenosis (VSS) stenting has been an effective treatment modality. Among patients who experience recurrent symptoms and develop new stenosis, the optimal treatment strategy is unknown. The aim of this study was to investigate the role of rescue re-stenting in patients with recurrence after prior successful stenting.

Methods: This was a single center, retrospective review from a prospectively maintained IIH registry. Between 2012 and 2023, patients who underwent interventions for confirmed IIH and angiographically demonstrable VSS were included. The cohort was divided into those who underwent a single stenting procedure (single …

How Different Is Invasive Coronary Physiology In The Left Anterior Descending Artery?, Nils P Johnson, K Lance Gould

Faculty, Staff and Student Publications

Given the large amount of myocardium supplied by the left anterior descending (LAD) artery, it understandably receives additional scrutiny during coronary angiography. However, these same features make the interpretation of pressure wire physiology more nuanced to avoid overtreatment. This review provides case examples to underpin an extensive literature review supporting the argument that a "positive" fractional flow reserve (FFR) in the LAD needs to be approached with caution. A large hyperemic gradient, or low FFR, can arise from either a severe and focal lesion in conjunction with low flow or diffuse disease coupled with intact or normal flow. Separating these …

In-Hospital Mortality And Hemorrhagic Risks In Traumatic Brain Injury Patients With Early Vs. Late Venous Thromboembolism, Sophie Samuel, Jalon Barnes, Lynn Yamane, Eugene Uh, Cyprian C Afunugo, Bosco Seong Kyu Yang, Huimahn Alex Choi

Faculty, Staff and Student Publications

Objective: This study reviewed the management and outcomes of traumatic brain injury (TBI) patients who developed venous thromboembolism (VTE) during hospitalization, focusing on the timing of VTE diagnosis and anticoagulation initiation.

Methods: This retrospective, single-center study utilized data from the University of Texas Trauma Database. Patients were categorized based on VTE diagnosis timing (early ≤7 days, late >7 days). The primary outcome was in-hospital mortality. Secondary outcomes included mortality specifically among patients who were receiving anticoagulation treatment, hemorrhagic complications, predictors associated with early anticoagulation initiation (defined as ≤ 7 days from VTE diagnosis), and whether anticoagulation timing influenced mortality.

Results: …

Steroids For Viral Meningitis: A Foe Or A Friend?, Rodrigo Hasbun

Faculty, Staff and Student Publications

No abstract provided.

The Symptom Burden Of Women With A Known Risk Of Breast Cancer Receiving Risk Reducing Medication, Meagan S Whisenant, Jessica Treviño Jones, Anneliese O Gonzalez, Therese Bartholomew Bevers, Kelly Brassil, Darcy A Ponce, Sharvari Kamat, Emily Solis, Ann Maliackal, Hannah Warlick, Amie Walters, Chloe Denham, Loretta A Williams

Faculty, Staff and Student Publications

Background: For the estimated 10 million women in the United States who meet the high-risk criteria for breast cancer, evidence-based interventions may reduce the risk of breast cancer by 50-65 %. Even with substantial evidence supporting preventive medication for risk reduction, there is significant lack of uptake and adherence. The purpose of this study was to characterize the experience of women at high risk for breast cancer and define the content domain for a patient-reported outcomes (PRO) measure of symptom burden from breast cancer risk and risk reducing medication.

Methods: Thirty women at high risk for breast cancer and receiving …

Radiographic Axial Spondyloarthritis (Ankylosing Spondylitis) Commencing Late In Life, Mark C Hwang, Karim Doughem, Minjae Lee, Lianne S Gensler, Mariko L Ishimori, Michael M Ward, Matthew A Brown, Amirali Tahanan, Michael H Weisman, Mohammad H Rahbar, John D Reveille

Faculty, Staff and Student Publications

No abstract provided.

Giant Cell Tumor Of The Bone With Fatal Pulmonary Metastasis: A Case Report, Mohamad Taha, Saadia A Faiz, Pushan Jani, Jing Liu, Yasir D Ali, Mohammad Asim Amjad

Faculty, Staff and Student Publications

Giant cell tumors of the bone are typically benign, locally aggressive lesions that rarely metastasize. In this report, we describe the case of a 48-year-old woman presenting with a giant cell tumor of the bone of the hip joint, which demonstrated aggressive histological features and recurrent behavior. The patient developed multiple unresectable pulmonary metastases despite several wide local excisions. Although pulmonary metastases from giant cell tumors of the bone are usually associated with a relatively favorable prognosis, guidelines for the optimal treatment of metastatic giant cell tumors of the bone remain limited. This case highlights the unpredictable nature of giant …

Thrombotic Storm With Antiphospholipid Syndrome In The Setting Of Relapsing Evans Syndrome And Systemic Lupus Erythematosus: A Case Report, Som Singh, Sergio Abraham Candiales, Zachary Hunzeker, Cristina Olivo Freites, Modupe Idowu

Faculty, Staff and Student Publications

Background: There are few cases that report the presence of lupus anticoagulant and antiphospholipid antibodies between Evans syndrome and the presence of lupus anticoagulant. However, differentiating between primary and secondary causes of Evans syndrome remains challenging.

Case description: A 31-year-old female with a medical history of autism spectrum disorder, antiphospholipid syndrome (APS), complete systemic lupus erythematosus (SLE), and Evans syndrome was admitted for cholecystitis requiring laparoscopic cholecystectomy. In the setting of her acute illness, her thrombocytopenia worsened. Her hospital course was then complicated by the development of a left adrenal hematoma and venous thrombosis. Anticoagulation therapy was conservatively held due …

Use Of Hookah And Age Of Asthma Onset Among Us Adults, Adriana Pérez, Sarah Valencia, Pushan P Jani, Melissa B Harrell

Faculty, Staff and Student Publications

Objective: To explore the association of hookah use on the age of asthma onset among adults who were asthma/COPD free and who did not use cigarettes, cigars, electronic cigarettes or smokeless tobacco prior to asthma onset.

Methods: Secondary data analyses were conducted of the waves 1-6 (2013-2021) of the US nationally representative Population Assessment of Tobacco and Health Study among adults (>18 years). The four hookahs use exposures evaluated were (1) past 30-day (P30D) hookah use at the first wave of participation, (2) total number of waves before asthma onset in which adults reported P30D hookah use, (3) total …

Changes In Medication Complexity And Post-Hospitalization Outcomes In Older Adults Hospitalized For Heart Failure, Aayush Visaria, William Mcdonald, John Mancini, Andrew P Ambrosy, Min Ji Kwak, Ashkan Hashemi, Mark S Lachs, Andrew R Zullo, Monika Safford, Emily B Levitan, Parag Goyal

Faculty, Staff and Student Publications

Introduction: Medication regimen complexity may be an important risk factor for adverse outcomes in older adults with heart failure. However, increasing complexity is often necessary when prescribing guideline-directed medical therapy at the time of a heart failure hospitalization. We sought to determine whether increased medication regimen complexity following a heart failure hospitalization was associated with worse post-hospitalization outcomes.

Methods: This retrospective cohort study included Reasons for Geographic and Racial Differences in Stroke (REGARDS) participants aged at least 65 years hospitalized for heart failure between 2003 and 2014. We calculated changes between hospital admission and discharge in medication count (Δcount) and …

Editorial: Women In Brain Imaging And Stimulation, Volume Ii: 2024, Molly S Hermiller, Ruogu Fang, Wen Li

Faculty, Staff and Student Publications

No abstract provided.

An Ontology-Based Method For Formalizing And Encoding Patient Colonoscopy Preparation Using Bpmn And Owl2 For Automated Tool Development, Muhammad Amith, Yue Yu, Yuheng Shi, Brooks Cash, Barani Mayilvaganan, Anirudh Babu, Yang Gong

Faculty, Staff and Student Publications

Colonoscopy is a proven procedure for mitigating the incidence of colorectal cancers in late adulthood. Despite its effectiveness, colonoscopy preparation presents several challenges for patients, including issues with adherence and misunderstanding. Information and communication technology (ICT) tools may offer valuable support for modern patients. To enable such tools, computable knowledge bases are essential. In this paper, we describe the development of an ontology-based knowledge graph representing four laxative-based pre-colonoscopy procedures. We used the business process modeling and notation and OWL2 formalisms to manifest machine-readable artifacts that model processes of colonoscopy preparation. Future work will focus on integrating extended knowledge bases …

Esomeprazole Inhibits Proliferation Of Scleroderma Fibroblasts Via Cell Cycle Regulation, Mohammad A Khan, Shaheer Koniyan, Manisha Ahir, Anil G Jegga, Maureen D Mayes, David Gius, Justin Leung, Mark D Bonnen, Sydney B Montesi, Yohannes T Ghebre

Faculty, Staff and Student Publications

Background: Scleroderma is a complex autoimmune disease characterized by abnormal fibroblast proliferation and excessive collagen deposits in the skin and internal organs. We previously showed that esomeprazole, an FDA-approved drug for gastric disorders, may prevent dermal fibrosis.

Methods: To test this, we evaluated the antiproliferative effect of esomeprazole and the underlying molecular mechanisms using primary fibroblasts derived from patients with scleroderma. BrdU incorporation, flow cytometry, immunofluorescence, Western blot analysis, RNA sequencing, and functional enrichment analysis were performed.

Results: Esomeprazole inhibited the proliferation of scleroderma fibroblasts in a dose-dependent manner, as measured by BrdU incorporation and Ki-67 marker. Intriguingly, esomeprazole arrested …

Oral Microbiome Brain Axis And Cognitive Performance In Older Adults, Darbaz Adnan, Phillip A Engen, Michelle Villanueva, Shohreh Raeisi, Vivian Ramirez, Ankur Naqib, Stefan J Green, Faraz Bishehsari, Lisa L Barnes, Ali Keshavarzian, Klodian Dhana, Robin M Voigt

Faculty, Staff and Student Publications

The human oral microbiota is a community of microorganisms that reside in the oral cavity, including lingual, buccal, and saliva, each niche with a distinct microbial composition. Alterations in oral microbiota have been associated with an increased risk of Alzheimer’s disease (AD). This study used data from 143 older adults in the MIND trial to evaluate the association between oral microbiome and cognitive function. Oral niche-specific differences (saliva, buccal, and lingual), as well as the microbiome composition differences (α and β diversity), were associated with cognitive function. A lower abundance of Gemella and a higher abundance of anaerobic pro-inflammatory bacteria …

Decline In Attrition Rates In United States Pediatric Residency And Fellowship Programs, 2007–2020: A Repeated Cross-Sectional Study, Emma Omoruyi, Greg Russell, Kimberly Montez

Faculty, Staff and Student Publications

Purpose: Declining fill rates in US pediatric residency and subspecialty programs requires trainee retention. Attrition, defined as transfers, withdrawals, dismissals, unsuccessful completions, or deaths, disrupts program function and impacts the pediatric workforce pipeline. It aims to evaluate attrition trends among pediatric residents and fellows in Accreditation Council for Graduate Medical Education (ACGME)-accredited programs from 2007 to 2020.

Methods: This repeated cross-sectional study analyzed publicly available ACGME Data Resource Book records. Attrition rates and 95% confidence intervals (CIs) were calculated overall and by subspecialty. Logistic regression assessed temporal changes; odds ratios (ORs) compared 2020 to 2007.

Results: From 2007-2020, pediatric residents …

National Landscape Of Underrepresented In Medicine Visiting Medical Student Programs In Pediatrics, Tyler K Smith, Rebecca Blankenburg, Ann E Burke, Emma A Omoruyi, Wendla Sensing, Tiffany Ruan, David D Williams, Onyi Oligbo, Lahia Yemane

Faculty, Staff and Student Publications

Objective: Underrepresented in medicine visiting medical student programs (UIM-VMSPs) have gained popularity across specialties as an intervention to diversify residency programs; however, no study has explored the national landscape of these programs in pediatrics. This study aimed to characterize program components, residency rank and match outcomes, benefits, challenges, and lessons learned about UIM-VMSPs in pediatrics nationally.

Methods: From September to December 2023, the authors conducted a national, cross-sectional, mixed methods study surveying program leaders of UIM-VMSPs identified on the Association of Pediatric Program Directors website. The authors used descriptive statistics to analyze the data and conventional content analysis for free-text …

Implantable Loop Recorder Identifies Sustained Ventricular Tachycardia In A Pediatric Patient Despite Negative Ep Study: A Case Report, Jia Yue Liu, Mohammed T Numan

Faculty, Staff and Student Publications

Experience of loop recorders in pediatric patients is limited. We report using a loop recorder to detect ventricular arrhythmias in a 16-year-old female who had years of palpitations despite inconclusive noninvasive and invasive electrophysiological testing.

Case Report: Coronary Vasospasm Precipitating Stemi And Polymorphic Ventricular Tachycardia-A Case Of Cardiotoxicity From 5-Fu Based Chemotherapy In A 41-Year-Old Woman, Ammar Hasnie, Zachary Neace, Kristin Ellison, Aaron Hesselson, Karam Ayoub, Mohammed Al-Yafi, Amit Arbune

Faculty, Staff and Student Publications

Background: Intravenous 5-fluorouracil (5-FU), in combination with oxaliplatin and folinic acid, makes up a chemotherapy regimen commonly referred to as FOLFOX. It is well-established for its efficacy in patients with advanced colorectal cancer; however, the benefits are accompanied by potential side effects that warrant careful consideration. Common toxicities can range from nausea and vomiting to neuropathy. Cardiotoxicities related to FOLFOX and fluoropyrimidines in general are extremely rare but can easily be fatal.

Case presentation: A 41-year-old woman who was recently diagnosed with stage IIIc colorectal cancer after she underwent a subtotal colectomy was admitted to the Oncology clinic for further …

Rho/Rock Pathway As A Therapeutic Target In Multiple Diseases, Zixiu Cheng, Shannon Erhardt, Jun Wang

Faculty, Staff and Student Publications

The Rho/ROCK (Rho-associated coiled-coil-containing protein kinase) signaling pathway plays a pivotal role in regulating diverse cellular processes, including cytoskeletal organization, cell migration, proliferation, and apoptosis. Dysregulation of this pathway has been implicated in the pathogenesis of various diseases, such as cardiovascular disorders, cancer, neurological conditions, and fibrotic diseases. Accumulating evidence supports the therapeutic potential of targeting Rho/ROCK, with several inhibitors currently under investigation or in clinical use. This review summarizes the molecular mechanisms underlying Rho/ROCK signaling, explores its involvement in disease progression, and discusses recent advances in the development of and the clinical application of ROCK inhibitors as promising therapeutic …

Revisiting Cytomegalovirus In Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients: Current Strategies For Prevention And Management In The Letermovir Era, Lisa Hiskey, Diego R Hijano, Ramia Zakhour

Faculty, Staff and Student Publications

CMV infection remains the most common clinically significant infection in pediatric allogeneic hematopoietic stem cell (HCT) recipients, with seropositive recipients of transplants from seronegative donors at the highest risk for complications. In recent years, letermovir, a novel antiviral with a favorable toxicity profile, was approved first for adults and more recently for pediatric patients for the primary prophylaxis of CMV infection and disease in high-risk HCT recipients. Growing evidence from real-life data regarding the safety and efficacy of letermovir has transformed the landscape of CMV disease in HCT transplant recipients and led to a paradigm shift from a preemptive approach …

Safety Of Indocyanine Green Microdosing For Clinical Imaging Of Csf Ventricular Dynamics And Extracranial Outflow, Miriam Zamorano, Banghe Zhu, Ahmed T Massoud, Jonathan Hendricks, H Alex Choi, Pedram Peesh, Brandon A Miller, Xinhai Robert Zhang, Manish N Shah, Eva M Sevick-Muraca

Faculty, Staff and Student Publications

Background and purpose: Intravenous administration of indocyanine green (ICG) has been approved in brain surgeries for decades, yet concerns about neurotoxicity prevent its direct administration into the cerebrospinal fluid (CSF). Armed with prior animal studies demonstrating the feasibility of using ICG microdosing into the CSF, we sought to evaluate its nonclinical safety profile and obtain surrogate measures in adults prior to its use in human neonates.

Methods: Evaluation of ICG toxicity was conducted in mixed primary CNS cell cultures and in an extended safety study of juvenile rat pups deploying intraventricular injections of saline (as control) or ICG. Analysis of …

Molecular, Histologic, And Clinical Characterization Of Methylation Class Pleomorphic Xanthoastrocytoma: An Analysis Of 469 Tumors, Christopher H Dampier, Niharika Shah, Kristyn Galbraith, Azadeh Ebrahimi, Osorio Lopes Abath Neto, Zied Abdullaev, Sanda Alexandrescu, Felipe Andreiuolo, Terri Armstrong, Tiffany Baker, Sahara Cathcart, Hye-Jung Chung, Patrick J Cimino, Kyle S Conway, Jennifer Cotter, Felipe D'Almeida Costa, Karen Dazelle, Nima Etminam, Sima Esther Ferman, Igor Fernandes, Christina K Ferrone, Ahmed Gilani, Mark Gilbert, Jason Gregory, Courtney Ketchum, Han Sung Lee, Ina Lee, Maria Beatriz S Lopes, Qinwen Mao, Michael S Marshall, Matthew Mccord, Stewart G Neill, Jeffrey J Nirschl, Byram H Ozer, Werner Paulus, Marta Penas-Prado, Marco Prinz, Peter Pytel, Martha Quezado, Mark Raffeld, Sharika Rajan, Miriam Ratliff, Guido Reifenberger, Lorraina Robinson, Jens Schittenhelm, Daniel Schrimpf, Omkar Singh, Christian Thomas, Diana Thomas, Jaiyeola Thomas-Ogunniyi, Angus Toland, Rust Turakulov, Rachael Vaubel, Nitin Wadhwani, Jing Wu, Caterina Giannini, Matija Snuderl, Sebastian Brandner, Andreas Von Deimling, Kenneth Aldape

Faculty, Staff and Student Publications

Background: Methylation class pleomorphic xanthoastrocytoma (mcPXA) comprises tumors with the DNA methylation signature of classical PXA but with a wider histologic spectrum, including overlap with glioblastoma (GBM).

Methods: To clarify the histologic and molecular scope of mcPXA and characterize its clinical behavior, a cohort of 469 tumor samples from 458 patients matching to mcPXA by the DKFZ classifier (v12.6 score ≥0.85) was interrogated.

Results: Patient median age was 23 years (range 1-73 years) with a female predominance (259 female/199 male). CDKN2A/B homozygous deletion was observed in 406 of 469 (87%) samples. In samples tested for BRAF p.V600E mutations (n …

Advancing Randomized Clinical Trials In Surgery: Role Of Exception From Informed Consent, Central Institutional Review Board, And Bayesian Approaches, Amelia W Maiga, Rebecca A Snyder, Lillian S Kao, Mehul V Raval, Mayur B Patel, Martin L Blakely

Faculty, Staff and Student Publications

No abstract provided.

Reducing Computed Tomography Use For Appendicitis Evaluation In A Pediatric Emergency Department: A Multidisciplinary Quality Improvement Initiative, Jennifer Hockenbury, Monica E Lopez, Caroline M Godfrey, Martin L Blakely, Melissa Danko, Marta Hernanz-Schulman, S Barron Frazier

Faculty, Staff and Student Publications

Introduction: Appendicitis is the most common pediatric surgical emergency, and computed tomography (CT) remains an overused diagnostic test for appendicitis. Our institutional rate of CT utilization for suspected appendicitis was higher than in peer children's hospitals, so we aimed to reduce CT utilization during the evaluation of pediatric appendicitis from 31.3% to 15% within 12 months.

Methods: From September 2021 to October 2022, we conducted a multidisciplinary quality improvement initiative among patients evaluated for appendicitis in the pediatric emergency department (PED). Interventions included standardizing evaluation with a clinical practice guideline, an order set in the electronic medical record for clinical …

Moving From Prognostication To Prevention Of Ssis In Lmics, Stephanie Martinez Ugarte, Mokunfayo O Fajemisin, Lillian S Kao

Faculty, Staff and Student Publications

No abstract provided.

Enhancing Trust In Ai For Healthcare: A Quantative Evaluation Of Explainable Methods In Clinical Decision Support Systems, Abdul Aziz Noor

Masters

The integration of Artificial Intelligence (AI) into healthcare has revolutionized Clinical Decision Support Systems (CDSS) by enabling sophisticated predictive capabilities. However, the opaque nature of many machine learning models, commonly referred to as "black-box" systems, poses significant challenges to their adoption in critical clinical settings where transparency, interpretability, and trust are paramount. This thesis addresses these challenges by developing a rigorous, mathematically grounded framework to evaluate Explainable AI (XAI) methods and enhance their integration into CDSS.

Respect And Submission In Contexts Of Transition: Reviewing Judicial Interpretation From R V Drybones To R V Montour, Joshua Nichols

Osgoode Hall Law Journal

Since the Truth and Reconciliation Commission of Canada's call in 2015 for the adoption and implementation of the United Nations Declaration on the Rights of Indigenous Peoples (UN Declaration), Canada has seen significant legislative developments. Notably, the Declaration of the Rights of Indigenous Peoples Act (DRIPA) in British Columbia, the United Nations Declaration on the Rights of Indigenous Peoples Act (UNDRIPA) at the federal level, and subsequent amendments to the Interpretation Act in British Columbia have introduced innovative frameworks for procedural implementation. However, these legislative actions pose unique challenges, particularly in their interpretation by the judiciary.

This paper navigates through …