Medicine and Health Sciences Commons^™

Chronobiology Of Meal Timing In Early-Stage Hypertension: A Controlled Feeding Pilot Study Investigating The Effects On Renal And Vascular Function, Natalie J. Bohmke, Brittany Barton, Patrice Wiecek, Paula Rodriguez-Miguelez, Dave L. Dixon, Youngdeok Kim, Salvatore Carbone, Danielle L. Kirkman

EVMS School of Health Professions Faculty Publications

Lifestyle intervention is critical for young adults with early-stage hypertension. A Western diet has negative effects on kidney function and blood pressure; however, time-of-day effects are understudied. We hypothesized that consumption of a Western-style meal that is misaligned with the endogenous circadian rhythm would have adverse effects on blood pressure, kidney function, and vascular function. Ten young adults with elevated blood pressure or stage 1 hypertension (means ± SD: 26 ± 8 yr, 50% female) underwent a randomized crossover, isocaloric controlled feeding intervention. Participants were allocated to receive a Western-style meal high in sodium, sugar, and saturated fat in the …

Crossing The Theory Threshold: The Pedagogical Potential Of Generative Artificial Intelligence In Educational Research, Amanda Burbage, Jennifer L. Styron

EVMS School of Health Professions Faculty Publications

Purpose

This paper presents findings from an educational research graduate course in which generative artificial intelligence (AI) was incorporated to strengthen learners' understanding of threshold concepts related to theoretical frameworks. Medical and health professionals often struggle with the transition from a clinical role into the educational research role.

Methods

The study posits that the use of generative AI will help learners understand and apply theoretical frameworks beyond a superficial level, furthering their understanding, constructing new knowledge, and strengthening their ability to develop sound educational research studies. Journal and AI transcripts were analyzed for 37 participants.

Results

Open-ended codes were grouped …

First-Generation Medical School Applicants: A Quantitative Study Designed To Identify Areas Of Educational Support, Bethsabe Romero, Amanda K. Burbage

EVMS School of Health Professions Faculty Publications

First-generation (First Gen) students are unique medical school applicants. Due to their lived experience, they approach patient care by prioritizing trust, comfort and understanding. They have proven ability to overcome obstacles and were found to be more resilient than their continuing generation (Cont Gen) peers. Despite these notable attributes, they face unique challenges in gaining medical school acceptance. There are very few quantitative studies examining this student subpopulation, and our study identifies characteristics of first-generation medical school applicants while highlighting areas of needed support. This cross-sectional study used deidentified Application and Matriculating Student Questionnaire survey data that was obtained from …

Sglt2 Inhibitors In Cardio-Oncology: A Systematic Review And Meta-Analysis, Luigi Spadafora, Marco Bernardi, Gianmarco Sarto, Beatrice Simeone, Erica Rocco, Salvatore Carbone, Laura Adelaide Dalla Vecchia, Roberto Franco Enrico Pedretti, Valentina Valentine, Rachele Di Mario, Maurizio Forte, Giacomo Frati, Antonio Abbate, Michele Golino, Francesco Versaci, Mariangela Peruzzi, Pierre Sabouret, Giuseppe Biondi Zoccai, Sebastiano Sciarretta

EVMS School of Health Professions Faculty Publications

Background

According to available evidence, sodium-glucose cotransporter-2 inhibitors (SGLT2i) may confer cardioprotection in patients with cancer undergoing chemotherapy.

Objectives

The objective of the study was to evaluate the impact of SGLT2i on all-cause mortality and heart failure (HF) outcomes in this population.

Methods

We searched PubMed, Cochrane CENTRAL, and Embase through August 2025 for studies of SGLT2i in adult patients with cancer. Random-effects models were used to pool effects for all-cause mortality and an HF composite (new-onset HF and/or HF hospitalization) in cancer patients >18 years. Meta-regression tested effect modification by beta-blockers, statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, age, and …

Turnover Time In Neuroangiography Suites: Comparison Between Cases Performed At An Ambulatory Neurosurgery Center Versus A Tertiary Hospital, Pui Man Rosalind Lai, Vinay Jaikumar, Erika L. Leasher, Varun Sridhar, Gustavo M. Cortez, Aimee C. Degaetano, Elad I. Levy

EVMS School of Health Professions Faculty Publications

Background:

Efficient turnover time (TOT) and adherence to first-start time (FST) in operating and angiography suites are critical for optimizing workflow, reducing costs, and maximizing patient satisfaction. Hospitals face challenges in maintaining these metrics due to operational constraints and unexpected emergent cases. Our goal was to compare TOT, FST, and total admission time for elective cases performed in angiography suites at an ambulatory neurosurgery center (ANSC) versus a tertiary hospital (TH).

Methods:

We conducted a retrospective analysis of data for patients who underwent elective diagnostic or interventional neuroendovascular procedures at the TH or ANSC from January 2024 through October 2024. …

Tramadol For Treatment Of Neurogenic Cough: A Retrospective Case Series, Benjamin Joseph Rubinstein, Sheela Saidha, John Todd Sinacori

Department of Otolaryngology (ENT) Faculty Publications

Objectives

Explore the efficacy of tramadol for neurogenic cough and describe the longitudinal treatment experience.

Methods

A retrospective case series of adults with chronic cough who were treated with tramadol for neurogenic cough. A complete response was defined as no pathologic coughing, and a partial response was defined as 50% or greater reduction in severity or frequency.

Results

Sixty-nine patients were included. 38% of patients reported a complete response with an additional 33% reporting a partial response. The most common successful dosing regimen was 50 mg BID. Age, gender, and BMI did not impact treatment response. Patients with a history …

Reply To: S. N. Katkuri Et Al. And H. Liu Et Al. On Early And Sustained Improvements In Sense Of Smell With Tezepelumab Treatment In Patients With Chronic Rhinosinusitis With Nasal Polyps (Waypoint), Joaquim Mullol, Joseph K. Han, Tanya M. Laidlaw, Claire Hopkins, Anju T. Peters, Oliver Pfaar, Martin Desrosiers, Stella E. Lee, Andrew P. Lane, Claudia Chen, Yun Chon, Sandhia S. Ponnarambil, Andrew Foster, Andrew W. Lindsley, Christopher S. Ambrose

Department of Otolaryngology (ENT) Faculty Publications

[Introduction] We thank Dr. S. N. Katkuri, Dr. H. Liu, and their coauthors [1, 2] for their interest in our recent publication describing the improvements in loss of smell symptoms with tezepelumab versus placebo in patients with uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) in the WAYPOINT trial (NCT04851964) [3]. We are grateful for the authors' feedback on the clinical significance of the data presented and their appreciation of the consistency observed across a range of baseline clinical characteristic and demographic subgroups.

Early And Sustained Improvements In Sense Of Smell With Tezepelumab Treatment In Patients With Chronic Rhinosinusitis With Nasal Polyps (Waypoint), Joaquim Mullol, Joseph K. Han, Tanya M. Laidlaw, Claire Hopkins, Anju T. Peters, Oliver Pfaar, Martin Desrosiers, Stella E. Lee, Andrew P. Lane, Claudia Chen, Yun Chon, Sandhia S. Ponnarambil, Andrews Foster, Andrew W. Lindsley, Christopher S. Ambrose

Department of Otolaryngology (ENT) Faculty Publications

Background

Loss of smell is a principal symptom of chronic rhinosinusitis with nasal polyps (CRSwNP), affecting health-related quality of life and posing a safety hazard.

Methods

WAYPOINT (NCT04851964), a phase 3, multicenter trial in adults with uncontrolled CRSwNP, randomized patients 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Changes from baseline in biweekly mean Nasal Polyposis Symptom Diary (NPSD) loss of smell item, University of Pennsylvania Smell Identification Test (UPSIT), and 22-item Sino-Nasal Outcome Test (SNOT-22) loss of smell/taste item scores, as well as anosmia (UPSIT score ≤18) prevalence, were assessed over 52 …

Progression Of Mild Sleep-Disordered Breathing In Children Managed With Watchful Waiting, Erin M. Kirkham, Stacey Ishman, Susan Garetz, Cristina M. Baldassari, Ron B. Mitchell, Christopher Liu, Ignacio E. Tapia, Lisa M. Elden, Fauziya Hassan, Sally Ibrahim, Kristie Ross, Mengqi Cen, Rui Wang, Susan Redline, Ronald D. Chervin

Department of Otolaryngology (ENT) Faculty Publications

Purpose

To identify clinical characteristics that may be associated with persistence or progression of mild sleep-disordered breathing (SDB) in children who are observed without surgery.

Methods

This is a secondary analysis of the control arm of the Pediatric Adenotonsillectomy Trial for Snoring (PATS), which randomized 458 children aged 3.0 to 12.9 years with mild SDB (snoring with obstructive apnea-hypopnea index [oAHI] <  3 events/hour) to early adenotonsillectomy (eAT) versus watchful waiting with supportive care (WWSC). Participants were assessed at baseline and 12 months with the Pediatric Sleep Questionnaire-Sleep-Related Breathing Disorder (PSQ-SRBD) scale and polysomnography (PSG). We tested for factors predictive of either (1) PSG progression defined by a 12-month oAHI ≥ 3 or (2) symptom persistence or progression defined by a 12-month PSQ-SRBD score ≥ 0.33.

Results

A total of 234 participants were observed (mean age 6.2 years, 111 [47%] female, 65 [28%] Black or African American, 37 [16%] Hispanic). Overall, only 13% (n = 20/150) progressed to an oAHI ≥ 3 on repeat PSG, …

Use Of Tezepelumab For Chronic Rhinosinusitis With Nasal Polyps By Eosinophilic Endotype: Waypoint Post-Hoc Analysis, Shigeharu Fujieda, Nobuyoshi Otori, Joseph K. Han, Tadataka Yabuta, Claudia Chen, Claudio Marchese, Andrews Foster, Sandhia S. Ponnarambil, Yun Chan, Brian J. Lipworth

Department of Otolaryngology (ENT) Faculty Publications

Background

The phase 3 WAYPOINT study (NCT04851964) reported that tezepelumab improved outcomes in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), including nasal polyp size, nasal congestion, and sinonasal symptoms, and reduced the need for surgery and systemic corticosteroids (SCS).

Objective

To evaluate the efficacy and safety of tezepelumab across Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis-defined eosinophilic chronic rhinosinusitis (ECRS) subgroups.

Methods

Adults with severe CRSwNP were randomized to tezepelumab 210 mg or placebo every 4 weeks. Coprimary end points were the change from baseline to week 52 in total Nasal Polyp Score and the biweekly mean Nasal …

Single Intratympanic Injection Of Proprietary Brain-Derived Neurotrophic Factor (Oto-413) In Subjects With Speech-In-Noise Hearing Impairment: A Randomized, Dose Escalating, Double-Blind, Placebo-Controlled Phase 1/2 Study, Alan C. Foster, Jeffery J. Anderson, David R. Moore, Morgan Oktela Fuentes, Yiwei Wang, Peter G. Volsky, K. Paul Boyev, Victoria A. Sanchez

Department of Otolaryngology (ENT) Faculty Publications

Purpose

To evaluate the safety and tolerability and exploratory efficacy of OTO-413, an intratympanic-administered, sustained release formulation of brain-derived neurotrophic factor (BDNF) in a thermoreversible gel, in participants with speech-in-noise hearing difficulties.

Methods

This was a single dose, dose-ascending, randomized, double-blind, Placebo-controlled Phase 1/2 study conducted at 7 enrolling clinical sites in the U.S. 110 participants (56% female) enrolled had self-reported speech-in-noise (SIN) difficulties that were confirmed by a SIN test and were randomized to OTO-413 or Placebo. OTO-413 dose range was escalated from 0.01 mg to 1.5 mg within 7 Cohorts. Safety evaluations included monitoring for treatment-emergent adverse events, …

American Board Of Emergency Medicine Report On Residency And Fellowship Training Information (2025-2026), Yvette Calderon, Barry Knapp, Felix K. Ankel, Ted Gaeta, Lynne Holden, Derek Linklater, Zeno St. Cyr Ii, Ernest Wang, Melissa Barton, Andrews R. Trotter, Kevin Joldersma, Robert G. Purosky, Michael Gottlieb

Department of Medicine Faculty Publications

The American Board of Emergency Medicine gathers extensive background information on Accreditation Council for Graduate Medical Education-accredited emergency medicine residency and fellowship programs, as well as the residents and fellows training in those programs. We present the 2026 annual report on the status of physicians training in Accreditation Council for Graduate Medical Education-accredited emergency medicine training programs in the United States.

Prevalence And Correlates Of Anxiety And Depression Symptoms Among Medical Students: The Role Of Student Debt Burden, Foroozan Afsharchi, Joshua F. Edwards, Kailash S. Ram, Jingru Huang, Valicia Hale, Ismail El Moudden

Department of Family and Community Medicine Faculty Publications

Background

This cross-sectional study examined whether anxiety and depression symptoms decrease as medical students progress through training (suggesting adjustment disorder) or persist (suggesting chronic conditions), while identifying associated risk factors, including student debt burden and treatment effectiveness.

Methods

We surveyed medical students (years 1-4) at VHS-ODU using a sociodemographic questionnaire and validated screening instruments (GAD-7 for anxiety and PHQ-9 for depression) via RedCap from September to November 2024.

Results

Among 126 students, Scores were higher in Years 2-3 than in Years 1 and 4, but differences by year were not significant (GAD-7 p=0.055; PHQ-9 p=0.352). Students with a prior mental-health …

Yk-4-250, A Synthetic Telmisartan-Tempol Conjugate: Crystal Structure Of A Stabilized Free Radical Containing An Angiotensin At₁ Receptor Inhibitor, Simon Friedrich, Yali Kong, Faik N. Musayev, Milton L. Brown, B. Frank Gupton

Department of Biomedical and Translational Sciences Faculty Publications

We report the first crystal structure of the telmisartan-tempol conjugate 2,2,6,6-tetramethyl-1-(λ'-oxidaneyl)piperidin-4-yl 4'-[(1,7'-dimethyl-2'-propyl-1H,3'H-[2,5'-bibenzo[d]imidazol]-3'-yl)methyl]-[1,1'-biphenyl]-2-carboxylate free radical (YK-4-250, C₄₂H₄₆N₅O₃), a dual-function inhibitor designed to target both the angiotensin II type 1 receptor (AT₁R) and reactive oxygen species (ROS). Structural analysis reveals a unique crystal architecture in which the nitroxide radical is stabilized within a sterically protected environment while preserving the telmisartan pharmacophore essential for high-affinity receptor antagonism. YK-4-250 is a novel small-molecule conjugate of telmisartan and tempol that incorporates a catalytic stabilized nitroxide radical and was rationally designed to mitigate gastrointestinal acute radiation syndrome (GI-ARS).

The Psychiatric Burden Of Hidradenitis Suppurativa: A Trinetx Analysis Of Sex-Specific Disparities In Mental Health And Medication Use, Emily Sheetz, Julia Feord, Collette Sholi, Parker Adams, Tamas Gal, Susan G. Kornstein, Arturo Saavedra

Department of Medicine Faculty Publications

Background:

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition associated with physical and psychological burden. Prior research has shown increased rates of depression and anxiety among individuals with HS; however, sex-based disparities in the prevalence of these mental health conditions in patients with HS remain underexplored.

Objective:

To evaluate sex-based differences in the prevalence of major depressive disorder (MDD), generalized anxiety disorder (GAD), and the prescribing of antidepressants and anxiolytics among patients with HS.

Methods:

Using the TriNetX database, we identified patients over the age of 18 who had a recorded diagnosis of HS. Propensity score matching based on …

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

Department of Medicine Faculty Publications

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

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

Successful Use Of Chimeric Antigen Receptor T-Cell (Car-T) Therapy With Lisocabtagene Maraleucel In A Renal Transplant Recipient With Refractory/Relapsed Diffuse Large B-Cell Lymphoma (Dlbcl), Waqqas Tai, Fatima Chaudhry, Nesreen Shahrour, Jessica Thomas, Afoma Anyadibe, Anuoluwa Oyetoran, Swathi Gopishetty, Precious Idogun, Dilip Samarapungavan, Jassim H. Sarmad, Ishmael Jaiyesimi

Department of Medicine Faculty Publications

This case describes a 53-year-old male with end-stage renal disease who developed monomorphic post-transplant lymphoproliferative disorder (PTLD) in the form of diffuse large B-cell lymphoma (DLBCL) after kidney transplantation. Despite initial treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), the patient's disease progressed, and he was referred for chimeric antigen receptor (CAR) T-cell therapy with lisocabtagene maraleucel (liso-cel). Given his post-transplant status, his immunosuppressive agents (tacrolimus and mycophenolate) were held, and prednisone was tapered to 5 mg daily to maintain minimal baseline immunosuppression. After lymphodepleting chemotherapy and liso-cel infusion, the patient experienced no significant toxicities, including cytokine release syndrome (CRS) …

Percutaneous Closure Of Ventricular Septal Rupture After Myocardial Infarction:, Thomas A. Cook, Simone K. Schumaecker, Anjani Patibandla, Nicholas J. Valle, Matthew R. Summers

Department of Medicine Faculty Publications

BACKGROUND: Ventricular septal rupture (VSR) following acute myocardial infarction is a rare but deadly complication with mortality rates exceeding 90% when left untreated. Coronary ischaemia leads to myocardial necrosis and friability resulting in septal rupture, most commonly 3-5 days post-infarction. The sudden development of a left-to-right shunt causes volume overload in the right ventricle, pulmonary vasculature, and left atrium, precipitating biventricular failure, and cardiogenic shock. Management requires careful consideration of timing and modality of closure along with stabilization with mechanical circulatory support in severe cases.

CASE SUMMARY: A 65-year-old female presented with anterior ST-segment elevation myocardial infarction complicated by VSR …

Dietary Intake Of Micro- And Nanoplastics: Potential Adverse Gi Effects On Microbiome, Inflammation, And Neoplasia, Michael Saadeh, Gordon Hong, Sana Rabeeah, Priyata Dutta, Edward C. Oldfield, Iv, David A. Johnson

Department of Medicine Faculty Publications

Micro- and nanoplastics (MNPs) are pervasive in food-contact environments and the human diet, positioning the gastrointestinal (GI) tract as the primary portal of entry and a plausible site of early biological effects. Human exposure is supported by detection of microplastics in stool and colon tissue, and emerging clinical studies report associations between fecal microplastic burden and GI disease states, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). Preclinical studies provide mechanistic plausibility, reporting that ingested MNPs can modulate microbial ecology, alter mucus membrane integrity, increase intestinal permeability through changes in cellular tight junction biology, and induce inflammatory gene expression. …

Association Of Valvular Disease Progression Using Echocardiographic Findings In A Large U.S. Cohort, Abes A. Bautista Neughebauer, Amin Yehya, Raymond L. Benza, Deepak Talreja

Department of Medicine Faculty Publications

Background

The prevalence of valvular disease in the US is approximately 2.5%. Given that over 5 million Americans are affected, it is crucial to find those at higher risk of progression. The goal of this paper is to uncover which patients are more likely to have valvular disease progression using demographic factors, EKG and echocardiogram (ECHO) findings.

Methods

This paper utilized the EchoNext Database, which pairs 100,000 electrocardiograms and echocardiograms based on specific structural heart disease labels. Univariate and multivariate logistic regression were used to find risk factors for progression for aortic stenosis (AS), aortic regurgitation (AR), mitral regurgitation (MR), …

Educational Case: Hidradenitis Suppurativa, Ryan C. Saal, Linnea Lackstrom Westerkam, Cristo A. Carrasco Mendoza, Paul B. George, Christopher J. Sayed

Department of Medicine Faculty Publications

[Introduction] The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see https://doi.org/10.1016/j.acpath.2023.100086.1¹

Objective SK1.1: Pathophysiology of changes in the skin. Describe the pathophysiologic basis for changes in the color, surface texture, swelling, temperature, and sensitivity of skin.

Competency 2: Organ system pathology, Topic: Skin (SK); Learning Goal 1: …

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

Department of Medicine Faculty Publications

Background and AIMS

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

Methods

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

Metabolic Dysfunction-Associated Steatotic Liver Disease And Circadian Rhythm: Current Understanding And Implications For Future Therapeutic Interventions, William K. Slover, Ashley V. Huang, Steve M. D'Souza, Edward C. Oldfield, David A. Johnson

Department of Medicine Faculty Publications

Metabolic dysfunction-associated steatotic liver disease (MASLD), defined by the American Association for the Study of Liver Diseases as hepatic steatosis with at least one cardiometabolic risk factor, affects approximately 30-40% of adults worldwide. This condition may progress to fibrosis, cirrhosis, and hepatocellular carcinoma. The rising prevalence, alongside obesity and type 2 diabetes, underscores the need for early risk stratification and integrated therapeutic strategies. Circadian homeostasis, orchestrated by the suprachiasmatic nucleus and core clock gene feedback loops, synchronizes hepatic metabolic pathways with environmental light-dark cycles. The objective of this review is to evaluate the role of circadian disruption and metabolic dysfunction …

Real-World Anti-Amyloid Therapy Beyond Traditional Symptomatic Populations: A Longitudinal Case Series, Jayoung Han, Yuan Fang, Darlingtina Esiaka, Olufunmilola Abraham

Mathematics & Statistics Faculty Publications

Introduction: Anti-amyloid monoclonal antibodies are approved as disease-modifying therapies for early Alzheimer’s disease (AD), but real-world evidence remains limited, particularly among individuals treated during preclinical or minimally symptomatic stages. This study characterized clinical and biomarker trajectories among anti-amyloid therapy recipients across disease stages.

Method: We conducted a longitudinal retrospective case series of three biomarker-positive individuals from the Alzheimer’s Disease Neuroimaging Initiative who received lecanemab or donanemab. Clinical, cognitive, cerebrospinal fluid, plasma biomarker, and amyloid PET data were examined.

Results: In all three cases, most of the observation period preceded anti-amyloid therapy initiation. Clinical trajectories varied by biomarker profile and treatment …

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). …

Decreased Exercise-Induced Pulmonary Capillary Recruitment In Pulmonary Arterial Hypertension, David Langleben, Stylianos E. Orfanos, Benjamin D. Fox, Michele Giovinazzo, Magali Kaddis, John D. Catravas

Bioelectrics Publications

The human lung normally accommodates exercise-induced cardiac output increases mainly via recruitment of non-concomitantly perfused pulmonary capillaries. Recruitment is detectable by measuring the first-pass transpulmonary metabolism of ³H-benzoyl-Phe-Ala-Pro, providing an estimate of functional capillary surface area (FCSA). Pulmonary arterial hypertension (PAH) results from luminal narrowing of small precapillary arterioles, reducing downstream perfused FCSA. We hypothesized that exercising PAH patients would not be able to recruit FCSA normally. We studied two patients with severe PAH. Despite exercising to maximal dyspnea, neither could recruit FCSA. These limited data are the first direct measurements of FCSA in exercising PAH patients.

Metabolic Reprogramming Following Mitochondrial Transfer Between Idh2-Mutant Chondrosarcoma Cells And A Normal B-Cell Line, Caleb Wyckoff, Christopher Osgood, Ellen Jing, Michael Stacey

Bioelectrics Publications

Background/Objectives: Chondrosarcoma, glioblastoma, acute myeloid leukemia, chronic lymphocytic leukemia, and cholangiocarcinoma cancers all contain mutations in the gene isocitrate dehydrogenase 2 (IDH2). The mutant IDH2 enzyme metabolizes alpha-ketoglutarate (αKG) into the potent oncometabolite D-2-hydroxyglutarate (D2HG) in the mitochondria of these cancers, leading to altered cellular metabolism. Emerging evidence suggests that mitochondrial transfer between cancer and recipient cells represents an important form of intercellular communication that may influence cellular metabolism. The presence of intercellular TNTs between IDH2-mutant chondrosarcoma cells motivated an investigation into mitochondria-associated physiological changes occurring during an intercellular exchange with immune cells. A mitochondrial transfer is a two-way …

Establishment And Histopathological Characterization Of A Kyse-30 Subcutaneous Xenograft Model Of Esophageal Squamous Cell Carcinoma, Pavel A. Solopov, Alayna Enos, Mantas Silkunas, Giedre Silkuniene, Eleni Zivla, Andrei G. Pakhomov, Olga N. Pakhomova

Bioelectrics Publications

Background/Objectives: Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with poor prognosis and limited treatment options, highlighting the need for reliable preclinical models for translational research. Although xenograft models are widely used in cancer biology, systematic characterization of subcutaneous ESCC models under defined implantation conditions remains limited. The objective of this study was to systematically compare implantation conditions and define histopathological and growth-related parameters that enable reproducible tumor establishment while maintaining a practical experimental window for therapeutic studies. Methods: We established and characterized a subcutaneous ESCC xenograft model using human ESCC cell line KYSE-30 implanted into immunodeficient J:NU mice. …

Combination Therapy With Hsp90 Inhibitors And Nanopulse Stimulation Synergistically Impedes Hepatocellular Carcinoma And Breast Cancer Growth In Mice, Christiana Dimitropoulou, Gagan Thangjam, Brittany P. Lassiter, Teresa Hooker, Ruben M. L. Colunga Biancatelli, John D. Catravas, Stephen J. Beebe

Bioelectrics Publications

Nanopulse Stimulation (NPS) represents a promising and innovative therapeutic approach to cancer. Heat shock protein 90 Inhibitors (HI), on the other hand, are currently under investigation in multi-drug chemotherapy trials for various types of malignancies. Here we present results of a combination therapy employing two HSP90 inhibitors (AUY-922 or 17-AAG) and NPS to ablate cancer growth. We firstly tested the inhibitors alone or in combination with NPS in vitro in N1S1 cells, and then into two models of orthotopic Hepatocellular Carcinoma (HCC) and 4T1-Luc breast cancer. NPS + HI reduced tumor growth more than the sum of HI and NPS …

Targeting Ptp4a3 And Kvx-053 Mitigates Alcohol-Amplified Sars-Cov-2 Spike Protein-Induced Acute Lung Injury, Pavel A. Solopov, Ruben Manuel Luciano Colunga Biancatelli, Elizabeth R. Sharlow, John S. Lazo, John D. Catavas

Bioelectrics Publications

Introduction: Chronic alcohol exposure is associated with increased vulnerability to acute respiratory distress syndrome (ARDS), and emerging evidence suggests that this susceptibility extends to the severe respiratory manifestations of COVID- 19. The SARS-CoV-2 Spike Protein S1 subunit (S1SP) can independently trigger robust inflammatory and vascular injury responses in the lung, and our prior work demonstrated that chronic alcohol consumption markedly intensifies these effects in mice. PTP4A3 phosphatase is a key regulator of inflammation and endothelial barrier function. In this study, we investigated whether the PTP4A3 inhibitor KVX-053 can counteract alcohol-enhanced S1SP-induced lung injury in K18-hACE2 mice.

Methods: Animals were maintained …