Digital Commons Network^™

Antiviral Activity And Mucosal Safety Of Novel Human-Milk-Inspired Antimicrobial Peptides, Nazita Yousefieh, Louise A. Ouattara, Maimoona Bhutta, Ishita M. Shah, Carolina Herrera, Gustavo F. Doncel

CONRAD Publications

Background: Sexually transmitted infections (STIs) remain a major global health concern, with over one million new curable cases reported daily and limited long-term treatment options. Additionally, there are limited treatment options for women with bacterial vaginosis (BV), a dysbiotic condition predisposing them to STIs. Computationally designed human-milk-inspired antimicrobial peptides (AMPs) are promising candidates for novel antiviral and antibacterial therapies. This study evaluated the cervicovaginal mucosal safety and antiviral activity of three human-milk-inspired AMPs (MAT-006, UCD-MAT-001, and UCD-MAT-002) previously shown to exhibit antimicrobial activity against BV-causing pathogens. Methods: AMP cytotoxicity and inflammatory responses were assessed in relevant genital tract cell lines …

Predicting Oral Hiv Pre-Exposure Prophylaxis Efficacy In Cisgender Women Across Pregnancy And Postpartum, Yifan Yu, Kristina M. Brooks, Gustavo F. Doncel, Brookie M. Best, Mark A. Marzinke, Mark Mirochnick, Peter L. Anderson, Landon Myer, Connie Celum, Renee Heffron, Jenell Coleman, Dvora L. Joseph Davey, Lanxin Zhang, Max Von Kleist, Craig W. Hendrix, Jeremiah D. Momper, Robert Bies, Rachel K. Scott

CONRAD Publications

Cisgender women face an increased risk of HIV acquisition during pregnancy and postpartum. Oral pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate (F/TDF) is recommended in pregnancy despite limited published pharmacokinetic (PK) and efficacy data during pregnancy. Altered PK during pregnancy may reduce prophylactic efficacy and necessitate higher adherence. Tenofovir alafenamide (TAF) is a newer tenofovir prodrug with higher tenofovir diphosphate (TFV-DP) exposure in peripheral blood mononuclear cells (PBMCs), but the prophylactic efficacy of F/TAF across different reproductive stages in women is understudied. We adapted a multiscale modeling framework to predict the prophylactic efficacy of F/TDF and F/TAF across …

Effects Of An Early-Onset Hfd On Hepatic Functioning In A 3xtg Model Of Ad, Matthias Hirst

Graduate Theses, Dissertations, and Problem Reports (ETD)

Background: Approximately 1 billion people currently live with obesity. Driven by factors such as a high-fat diet (HFD), this pathology can have drastic effects throughout the body, with the liver in particular being a main target of its downstream consequences. Although it is capable of storing lipids, excess fat can conglomerate in the liver and contribute to various hepatic pathologies. A specific pattern of hepatic dysfunction seen in response to an HFD is increased acetylation of mitochondrial proteins. Further, expression and activity of insulin-degrading enzyme (IDE), involved in the degradation of Aβ, are altered in response to an HFD. Aβ …

Integrating Genetic Modifier Genotype With Serum Proteomics In Duchenne Muscular Dystrophy Clinical Trials Links Ltbp4 Genetic Modifier To Il-23/Cd93 Pathways In Muscle, Utkarsh J. Dang, Yuan Fang, Daniele Sabbatini, Elena Pegoraro, Luca Bello, Paula R. Clemens, Michela Guglieri, John Van Den Anker, Jesse Damsker, Laura Hagerty, Yetrib Hathout, Michael Ziemba, Lauren Morgenroth, Surajit Bhattacharya, Kanneboyina Nagaraju, Jyoti K. Jaiswal, Eric P. Hoffman

Mathematics & Statistics Faculty Publications

Genetic modifiers of Duchenne muscular dystrophy (DMD) that alter disease severity or response to therapy have been reported using natural history or registry data sets of older corticosteroid-treated patients. We tested associations of genetic modifiers on motor function outcomes in young (4 to <  7 years) steroid naïve clinical trial participants. Participants in clinical trials (VBP15-002/003 [n = 48]; VBP15-004 [n = 121]; DNA available for n = 110) were genotyped for eight published genetic modifier loci, and associations of genotypes with baseline motor function defined via an age-adjusted linear model. Corticosteroid drug response was modeled by genotype-stratified placebo vs. steroid treatment at 12- and 24-weeks posttreatment (mixed model for repeated measures). …

Modulating Oran Nitrate-Reducing Bacteria To Enhance Nitric Oxide Bioavailability As A Therapeutic Target For Atherosclerosis, Donovan C. Davidson

CMC Senior Theses

Atherosclerosis remains the primary driver of global cardiovascular disease, yet clinical interventions are largely restricted to high-cost, invasive procedures only after it has reached a critical stage. Recent research has identified a connection between the oral microbiome and vascular health via the enterosalivary nitrate-nitrite-nitic oxide (NO) pathway. Oral nitrate-reducing bacteria (ONRB) drive the synthesization of NO by reducing dietary nitrate into nitrite, which is then converted into bioavailable NO. NO is a potent vasodilator that maintains endothelial health by suppressing inflammation through inhibiting the expression of adhesion molecules VCAM-1 and ICAM-1. However, this pathway is easily compromised by dysbiotic oral …

Prevalence And Spectrum Of Genitourinary Anomalies In Children With Anorectal Malformations, Adnan El-Ghazaly, Tamer A. Wafa, Ahmed M. Negm, Adham W. El-Saied

Mansoura Medical Journal

Background: Anorectal malformations (ARMs) encompass a broad range of congenital defects and are frequently associated with genitourinary (GU) anomalies, which may contribute to long-term morbidity if undetected. This study aimed to determine the prevalence and spectrum of GU anomalies in children with ARMs, describe the urological and genital findings, and assess associations with sex and ARM type.

Patients and Methods: A prospective survey enrolled children diagnosed with ARMs at a tertiary pediatric surgery center. All patients underwent standardized clinical assessment, including focused genital examination and structured imaging. Abdominal ultrasonography (US) served as baseline screening for urinary tract anomalies. Voiding cystourethrogram …

Short Term Echocardiographic And Clinical Assessment Of Aortic Valve Neo-Cuspidization (Ozaki Procedure) In Comparison With Mechanical Aortic Valve Replacement, Amr Mohamed Ahmed Elshabrawy, Mohamed A. Gabr, Eid M Daoud, Mohammed Sanad, Sherif Arafa

Mansoura Medical Journal

Background: Aortic valve neo-cuspidization (AVNeo, Ozaki procedure) has emerged as an alternative to conventional aortic valve replacement, aiming to preserve native aortic root dynamics and improve postoperative hemodynamics. The replacement of the aortic valve presents challenges because both biological and mechanical prostheses have notable limitations.

Aim: To evaluate the short-term clinical and echocardiographic outcomes of aortic valve neocuspidization (Ozaki procedure) compared with mechanical aortic valve replacement (AVR) in patients with isolated aortic valve disease.

Patients and methods: This prospective comparative observational study included 42 adult patients with isolated aortic valve disease. 20 patients underwent AVNeo (Ozaki procedure) and 22 …

Assessing Access To Orthopaedic Care For Patients With Osteogenesis Imperfecta, Annemarie K. Leonard, Kara Ayers, Lauren Faokunla, Kaeli Samson, Erika Carter, Tracy Hart, Maegen Wallace

Graduate Medical Education Research Journal

Background. Osteogenesis Imperfecta (OI) is a rare disorder caused by variations in collagen. Clinical manifestations include multiple fractures, short stature, scoliosis, blue sclera, hearing loss, and opalescent teeth. Patients often need many different medical providers frequently, which may place financial burdens on families. This study sought to identify and understand barriers to care for children with OI.

Methods. We utilized an Institutional Review Board (IRB)-approved survey for primary caregivers of children with OI. Questions included demographic data, type of health insurance, history of and reasons for insurance denials, access to multidisciplinary OI care, and travel to receive OI care. The …

Salt Vs. Scalpel: A Surprisingly Simple Solution To Pyogenic Granulomas, Richard M. Regester, Kimberly Eisenstein

Graduate Medical Education Research Journal

Background. Pyogenic granulomas (PGs) are benign vascular lesions commonly encountered in primary care settings. They are often linked to trauma, hormonal changes, infections, or medications. While traditional treatments such as excision, curettage, and silver nitrate application are the treatment of choice, recurrence is possible, and they may result in discomfort, anxiety, or scarring. This case highlights the successful use of salt packing, a low-cost, minimally invasive alternative, for a PG resistant to conventional therapy.

Case. A 57-year-old female presented with a 10 mm PG on the right ventral thumb, which bled intermittently and increased in size over three months. An …

A Blood-Based Test For Colorectal Cancer Screening, Joshua Cullison

HCA Healthcare Journal of Medicine

Within the United States (US), colorectal cancer (CRC) remains the fourth most common malignancy and is responsible for over 50 000 deaths annually, second only to lung cancer in cancer mortality. Despite increased public awareness and increasing screening rates, the US remains far below the 80% screening mark set by the National Colorectal Cancer Roundtable at 59%. The addition of non-invasive blood-based tests for CRC screening could potentially increase screening rates and lower CRC deaths.

I performed a PubMed search using the search term “blood-based colorectal cancer screening.” I was particularly interested in articles that looked at Shield, which is …

A Colorful Enigma: A Case Of Orange Palpebral Spots In A 63-Year-Old Woman, Obarikanemi Nwogu, Karl Kellawan

HCA Healthcare Journal of Medicine

Background

The thin, vascularized skin of the eyelids makes them prone to irritation and discoloration, potentially revealing underlying issues, such as subcutaneous deposits, and an abundance of pigments like carotenoids and lipofuscins. First described in 2008 by Assouly et al, orange palpebral spots (OPS) present as painless orange-yellow lesions on the upper eyelids, primarily affecting White women with Fitzpatrick skin types I to III. Despite various hypotheses, the exact cause of OPS remains elusive, with no established links to malignancy or systemic illnesses.

Case Presentation

A 63-year-old woman, with a medical history including basal and squamous cell carcinoma, diabetes mellitus, …

An Unusual Presentation Of Lichen Planus Pigmentosus Inversus Responsive To Topical Tacrolimus: A Case Report, Valeria J. Gonzalez-Molina, Sujitha Yadlapati, Michael R. Hohnadel, Rick Lin

HCA Healthcare Journal of Medicine

Background

Lichen planus pigmentosus inversus (LPPI) is a rare variant of lichen planus pigmentosus (LPP), characterized by sharply defined violaceous-brown to gray macules, papules, patches, or plaques primarily affecting the intertriginous and flexural areas. Unlike LPP, which predominantly affects Fitzpatrick skin types III to IV in sun-exposed areas, LPPI spares these regions and has been predominantly reported in White and Asian patients.

Case Presentation

We discuss a 66-year-old man with Fitzpatrick skin type III who presented with a year-long history of mildly itchy, hyperpigmented plaques on the inframammary folds. These plaques developed after being hospitalized for a chronic urinary tract …

Presentation Of Cutaneous Large B-Cell Lymphoma, Leg Type, Francisca I. Valenzuela, Michael R. Hohnadel

HCA Healthcare Journal of Medicine

A man over the age of 89 presented with 2 violaceous, ulcerated plaques on his left lower leg, which developed over a 4-month period following a fall. The patient reported the initial formation of a solitary lump, which gradually enlarged and began bleeding a few weeks before his clinic visit. A histological examination of 2 biopsy samples revealed a dermal proliferation of large, severely atypical lymphoid cells with mitotic figures. Immunohistochemistry showed positivity for CD20, Bcl2, Bcl6, and MUM1, with cytokeratin 20 (CK20) negativity and a high percentage (80%-90%) of C-MYC positivity, which was consistent with a primary cutaneous diffuse …

The Top Twenty-Five Most Influential Articles In Surgery For Colorectal Cancer, Dana Poloni, Andrew Anklowitz, Fred Kobylarz, Christina Monaco Poloni, Ankit Dhiman, Pamela Burgess, Andrew Schlussel

HCA Healthcare Journal of Medicine

Background

This article provides surgical trainees with a ranked list of the foundational literature that guides the contemporary surgical management of colorectal cancer and shows the evolution of surgical techniques in the field.

Methods

We assessed the surgical literature using the Web of Science and other ranking systems to create a ranked list of published articles on colorectal cancer surgery.

Results

We compiled a ranked list of the top 25 articles in the surgical management of colorectal cancer, based on the citation density score (mean number of citations per year) and the individual author H-index. The mean density score of …

Pengaruh Ivabradin Terhadap Variabilitas Detak Jantung Pada Gagal Jantung Dengan Fraksi Ejeksi Rendah Akibat Penyakit Jantung Koroner, Handy Kurnia, Charles Limantoro, Friska Anggraini Helena Silitonga, Andreas Arie Setiawan

Jurnal Penyakit Dalam Indonesia

Introduction. Heart failure is one of the major challenges in global health due to its significant contribution to morbidity and mortality. One of the pathophysiological aspects is autonomic nervous system dysfunction which can be monitored through heart rate variability (HRV) parameters. Ivabradine is a pharmacological agent that potentially improves the balance of sympathetic and parasympathetic tone. This study was designed to evaluate the impact of ivabradine administration on HRV parameters in heart failure with reduced ejection fraction (≤40%) due to coronary heart disease in Indonesian population.

Methods. This study used a quasi-experimental research type with a pretest and posttest …

Polisitemia Sekunder Pada Pasien Laki-Laki Muda Dengan Sindrom Nefrotik, Ariani Intan Wardhani, Pringgodigdo Nugroho, Ikhwan Rinaldi, Meilania Sarasawati, Monik Ediana Miranda, Agnes Stephanie Harahap

Jurnal Penyakit Dalam Indonesia

Polycythemia is a condition characterized by an abnormal increase in the total red blood cell mass and is classified into primary and secondary polycythemia. Secondary polycythemia occurs as a physiological response to tissue hypoxia or increased erythropoietin production, without intrinsic abnormalities in erythroid progenitor cells. This condition is rare, particularly when associated with nephrotic syndrome. This report aims to describe a case of secondary polycythemia associated with focal segmental glomerulosclerosis (FSGS). A 20-year-old man presented with generalized edema for five months prior to admission, accompanied by foamy urine. Physical examination revealed peripheral edema and minimal ascites. Laboratory investigations demonstrated massive …

A Novel Mathematical Model Of Hiv Transmission Incorporating The Effects Of Treatment And Pre-Exposure Prophylaxis: Sensitivity Analysis And Numerical Simulations, Erick Manuel Delgado Moya

Mathematical Modelling and Numerical Simulation with Applications

Human immunodeficiency virus (HIV) continues to be a public health problem in many countries of the world, and Pre-exposure prophylaxis (PrEP) is a preventive method for HIV, which has shown great efficacy and is in use worldwide. This work presents a new mathematical model for HIV transmission incorporating PrEP use and evaluates the impact of PrEP along with its increasing use in a population. The construction of the model takes into account three forms of diagnosis: diagnosis of individuals in risky sexual contact, diagnosis after risky contact (diagnosis in the undiagnosed infected compartment), and diagnosis associated with attempting to enter …

Cytomegalovirus As A Potential Trigger For Acute Coronary Syndrome: A Case Of Nstemi In A Previously Healthy Patient, Hussam Al Hennawi, Muhammad Sabri, David Teng, Maxwell Berman, Botros Shenoda

Abington Jefferson Health Papers

Cytomegalovirus (CMV) infection has been implicated in endothelial dysfunction and atherogenesis, yet its role as a potential trigger for acute coronary syndrome (ACS) remains underrecognized. We present a case of a 32-year-old male with no prior medical history who developed non-ST elevation myocardial infarction (NSTEMI) and was subsequently found to have active CMV infection. The patient had no known history cardiovascular disease, though subsequent testing did reveal additional underlying risk factors. This case highlights the need to consider infectious etiologies, including CMV, as contributors to ACS in young, otherwise apparently healthy individuals. Understanding the interplay between viral infections and atherosclerotic …

Inflammatory Co-Regulation Of Voltage-Gated Sodium Channels And Na,K-Atpase In Metastatic Breast Cancer, Steven D. Scahill, Kelly Jean Sherman, Dennis Paul

School of Graduate Studies Faculty Publications

Sodium regulation is a potentially major driver of cancer metastasis. Voltage-gated sodium channels (VGSCs) and Na,K-ATPase are sodium transporters that are upregulated in many advanced carcinomas and are implicated as metastatic drivers. However, little is known about what drives this overexpression, how these proteins influence metastatic behavior, or whether these complementary sodium transporters are co-regulated in cancer. Using sodium transporter regulation in healthy neurons as a model, the present study demonstrated that the inflammatory mediator tumor necrosis factor alpha (TNFα) affects the expression of VGSCs and Na,K-ATPase in an in vitro model of metastatic breast cancer. Acute TNFα challenge increased …

Us Drug Policy Does Not Align With Experts' Rankings Of Drug Harms: A Multi-Criteria Decision Analysis, Michael Broman, Alan K. Davis, Stacey Armstrong, Adam Levin, Kaltum Ahmed, Gustavo A. Angarita, Brooke J. Arterberry, Cecilia Bergeria, Mitch Earleywine, Kathryn S. Gex, Tom Gregoire, Jamey J. Lister, David S. Mathai, Nicky J. Mehtani, Nathan Menke, Charles D. Nichols, Hillary Shaub, Alayna P. Tackett, Brandon Weiss, Nefize Yalin, Lawrence D. Phillips

School of Medicine Faculty Publications

Background United States drug policy is primarily based on the Controlled Substances Act of 1970 and largely contradicts scientific evidence about how to mitigate drugs' harms. Expert consensus on drug harms could inform policy that improves the health of people who use drugs while reducing negative societal impacts of drug use. Therefore, this study adapted and extended the relevant 2010 United Kingdom multi-criteria decision analysis, rating drug harms by criteria comprising health and social impacts to people who use drugs and their families, communities, and society.Methods Seventeen experts on drug use in the US, including three with lived experience of …

Disruption Of Protein-Protein Interaction Hotspots In The C-Terminal Domain Of Mlh1 Confers Mismatch Repair Deficiency, Keri M. Fishwick, Diego Gomez Vieito, Giada Greco, Giulio Collotta, Marco Gatti, Anastasija A. Kulik, Raphaël Guérois, Ivan Corbeski, Ashutosh S. Phadte, Issam Senoussi, Petr Cejka, Anna Pluciennik, Antonio Porro, Alessandro A. Sartori

Department of Biochemistry and Molecular Biology Faculty Papers

MutLα, a heterodimer of MLH1 and PMS2, plays a key role in DNA mismatch repair (MMR), which maintains genomic stability by correcting replication errors. Loss of MLH1 function causes MMR deficiency (MMRd), leading to elevated mutation rates and increased cancer susceptibility. However, MMRd can offer a therapeutic advantage, as high tumour mutational burden enhances the efficacy of immune checkpoint inhibition. MMR also drives somatic expansion of CAG repeats linked to Huntington’s disease (HD) pathogenesis. The C-terminal domain (CTD) of MLH1 contains at least two distinct protein–protein interaction (PPI) sites. The S1 site supports heterodimerization with the PMS2 endonuclease, whereas the …

The Effect Of Neoadjuvant Chemoradiotherapy On Perioperative Outcomes In Rectal Cancer Patients Following Stoma Reversal-A Retrospective Cohort Analysis, Mary Junak, Rosemarie Turk, Mohammad Afaque Alam, Eli Thompson, David Schaub, Joseph Gunderson, Anesu S. Masango, Srikar Kollipara, Andrea Moreno, Daniom Tecle, Valentine N. Nfonsam

School of Medicine Faculty Publications

BACKGROUND: Anastomotic leak after reversal of an ostomy is a significant complication in rectal cancer patients. The effects of neoadjuvant chemoradiotherapy (NCRT) on outcomes following stoma reversal are not well established. The aim of our study was to evaluate the effect of NCRT on outcomes in rectal cancer patients following stoma reversal. METHODS: We performed a [2005-2012] retrospective cohort analysis of the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP), including adult (≥18 years) rectal cancer patients who had elective stoma reversal. Patients were stratified into those who received NCRT and those who did not. Primary outcomes were anastomotic …

Low Utilization Of Intracavernosal Injection And Penile Doppler Ultrasound In The Evaluation Of Erectile Dysfunction And Peyronie's Disease, Joon Yau Leong, Tyler Gaines, Zachary J. Prebay, David Ebbott, Paul H. Chung

Department of Urology Faculty Papers

INTRODUCTION: Despite the diagnostic value of intracavernosal injections (ICI) and penile Doppler ultrasound (PDUS), there remain barriers to widespread clinical adaptation of these methods. The study aimed to evaluate the practice patterns of utilization of ICI and PDUS in the assessment of erectile dysfunction (ED) and Peyronie's disease (PD).

METHODS: Using the TriNetX database (Cambridge, MA, USA), adult (≥18 years) male patients with a diagnosis of ED on oral phosphodiesterase-5 (PDE5) inhibitors were identified. Current Procedural Terminology codes were utilized to identify patients who underwent further evaluation with ICI or PDUS, as well as penile prosthesis placement after PDUS. A …

Mathematical Analysis And Numerical Simulation Of A Fractional-Order Sir-Si Model For Malaria Transmission Dynamics, Gassan A. M. O. Farah, Abdulaziz Y. A. Mukhtar, Kailash C. Patidar

Mathematical Modelling and Numerical Simulation with Applications

This study investigates the complex transmission dynamics of malaria, a critical global health challenge, with a focus on the African continent. We introduce a novel approach that employs Fractional Differential Equations (FDEs) to advance the understanding of malaria spread and control. Specifically, we develop a new SIR-SI model using the Caputo fractional operator, which captures the memory effects and time-delay characteristics inherent in real-world epidemiological systems. A detailed analysis of the model's solvability and uniqueness is conducted using fixed-point theory. To obtain an analytical solution, the system is solved via the Laplace transform method, with solutions expressed in closed form …

Metastatic Uveal Melanoma Surveillance: A Delphi Panel Consensus, Juan Alban, R. Christopher Bowen, David A. Reichstein, Meredith Mckean, Jose Lutzky, Ezekiel Weis, Richard D. Carvajal, Susan Dulka, Brian G. Morse, Marcus O. Butler, Suthee Rapisuwon, Kevin B. Kim, Sanjay Chandrasekaran, Allison Betof Warner, Jonathan S. Zager, Bartosz Chmielowski, Sapna P. Patel, Leonel Fernando Hernandez-Aya, Zelia M. Correa, Leslie A. Fecher, Yana G. Najjar, Kamaneh Montazeri, Alexander N. Shoushtari, Asad Javed, Dan S. Gombos, April K. S. Salama, Katy Tsai, Frank H. Miller, Nikhil Khushalani, Rino S. Seedor, Evan J. Lipson, Sunil A. Reddy, Elizabeth Buchbinder, Shailender Bhatia, Anna Pavlick, Inderjit Mehmi, Thomas Aaberg, Alexandra P. Ikeguchi, Ivana K. Kim, Scott D. Walter, Arun D. Singh, Ryan J. Sullivan, Jacob S. Choi, Basil K. Williams, Marlana Orloff, Prithvi Mruthyunjaya, Megan D. Schollenberger, Namita Gandhi, J. William Harbour, Sunandana Chandra

Department of Radiology Faculty Papers

BACKGROUND/OBJECTIVES: Uveal melanoma is a rare but aggressive intraocular malignancy that metastasizes in up to half of patients, most commonly to the liver, despite effective local treatment. In the absence of robust evidence, there are no standardized guidelines for post-treatment surveillance, resulting in wide variation in imaging modalities, frequency, and duration across physicians and institutions. This study aimed to develop expert consensus recommendations for surveillance strategies in patients with uveal melanoma.

METHODS: A modified Delphi method was conducted across three iterative survey rounds between September 2024 and February 2025 using an online platform. Panelists included medical oncologists, ocular oncologists, radiologists, …

Microglial Expression Of Serotonin Receptors Reveals Parallel Regulation Of 5-Ht2b And Bdnf In The Rat Hippocampus, Andrei Turkin, Maria Sidorova, Ekaterina Kurilova, Natalia Alenina, Oksana Tuchina, Friederike Klempin

School of Graduate Studies Faculty Publications

Growing evidence suggests that psychiatric disorders are characterized by a prolonged inflammatory state, which may influence the efficacy of compounds targeting serotonin. Serotonin is a key signaling molecule in neuroplasticity of the adult hippocampus and involved in antidepressant action. Recent in vitro studies indicate the neurotransmitter may also facilitate the response to inflammation and potentially modulate microglial function towards neuroprotection. Using Tph2−/− rats depleted of brain serotonin, we examined microglial expression of various serotonin receptors (5-HTRs) in vivo in both the hippocampus and prefrontal cortex and assessed mRNA levels of cytokines and brain-derived neurotrophic factor (BDNF). We observed age-dependent and …

Isg15 Dysregulates Endoplasmic Reticulum-Mitochondrial Contacts And Calcium Homeostasis In Ataxia Telangiectasia, Oygul Mirzalieva, Ryan E. Reed, Arthur L. Haas, Meredith A. Juncker, Patrick Logarbo, Jennifer M. Klein, David Worthylake, Shyamal D. Desai

School of Graduate Studies Faculty Publications

Dysregulation of endoplasmic reticulum and mitochondrial (ER:Mit) contacts and mitochondrial calcium (mitCa2+) homeostasis are found in several neurodegenerative disorders, including Ataxia Telangiectasia (A-T). However, the cellular basis of these defects remains unclear. Previously, we demonstrated that the aberrantly elevated Interferon-Stimulated Gene 15 (ISG15) pathway inhibits protein polyubiquitylation, its dependent protein turnover, and mitophagy pathways in A-T. Literature indicates that silencing of mitochondrial ubiquitin ligase 1 (MUL1) stabilizes mitofusin2 (MFN2) and attenuates mitCa2+ uptake from ER to Mit (mitCa2+influx) in primary neurons. We have replicated these findings in apparently healthy fibroblasts. We hypothesized that elevated ISG15 may inhibit ubiquitin-dependent MUL1-mediated degradation …

Subgroup Analyses Of The Phase 3 Focus Study Of Melphalan/Hepatic Delivery System In Patients With Unresectable Metastatic Uveal Melanoma, Jonathan S. Zager, Marlana Orloff, Pier Francesco Ferrucci, Junsung Choi, David J. Eschelman, Evan S. Glazer, Aslam Ejaz, Erika Richtig, Sebastian Ochsenreither, Sunil A. Reddy, Michael C. Lowe, Georgia M. Beasley, Anja Gesierich, Martin Gschnell, Reinhard Dummer, Ana Arance, Stephen William Fenwick, Joseph J. Sacco, Johnny John, Matthew Wheater, Christian H. Ottensmeier

Department of Medical Oncology Faculty Papers

PURPOSE: To assess efficacy and safety in subgroups of patients treated with Melphalan/Hepatic Delivery System (melphalan/HDS), a drug/device combination for liver-directed treatment of metastatic UM (mUM) patients. Previously reported FOCUS study results indicated melphalan/HDS treatment provides a clinically meaningful response rate and favorable benefit-risk ratio in patients with unresectable mUM.

METHODS: Patients with mUM received treatment with melphalan (3.0 mg/kg ideal body weight) every 6-8 weeks for up to 6 cycles. Post hoc analyses of efficacy and safety were conducted for patient subgroups based on demographic and baseline disease characteristics.

RESULTS: 102 patients with mUM were enrolled; treatment was attempted …

Application Of Flexible Endoscopy For Gastrointestinal Foreign Body Removal In A Leopard Gecko (Eublepharis Macularius), Jang-Hee Han, Seung Yoon Ahn, Do Na Lee, Seong Chan Yeon

The Thai Journal of Veterinary Medicine

A male captive-bred leopard gecko (Eublepharis macularius) presented with a history of inadvertent ingestion of a rubber tip from forceps during feeding. The foreign body was impalpable on physical examination, while radiographic evaluation confirmed its presence in the stomach. Considering the procedural risks associated with invasive surgical interventions, endoscopic retrieval under general anesthesia was pursued. An initial attempt using a 2.8 mm superfine flexible endoscope with 0.8 mm forceps was unsuccessful due to insufficient stability, which hindered effective navigation to the foreign body. In contrast, a second attempt using a larger 9.2 mm flexible endoscope with 2.3 mm …

Role Of Gut Microbiome In Oncogenesis And Oncotherapies, Renuka Sri Sai Peddireddi, Sai Kiran Kuchana, Rohith Kode, Saketh Khammammettu, Aishwarya Koppanatham, Supriya Mattigiri, Harshavardhan Gobburi, Suresh K. Alahari

School of Graduate Studies Faculty Publications

The gut microbiome has emerged as a key regulator of human health, influencing not only metabolism and immunity but also the development and treatment of cancer. Mounting evidence suggests that microbial dysbiosis contributes to oncogenesis by driving chronic inflammation, producing genotoxic metabolites, altering bile acid metabolism, and disrupting epithelial barrier integrity. At the same time, the gut microbiome significantly modulates the host response to oncotherapies including chemotherapy, radiotherapy, and especially immunotherapy, where microbial diversity and specific taxa determine treatment efficacy and toxicity. This review synthesizes current evidence on the role of the gut microbiome in both oncogenesis and oncotherapies, focusing …