The Interplay Of Oxidative Stress, Mitochondrial Dysfunction, And Neuroinflammation In Autism Spectrum Disorder: Behavioral Implications And Therapeutic Strategies, Ansab Akhtar, S K. Rahaman

School of Medicine Faculty Publications

Autism spectrum disorder (ASD) deals with several symptoms, including language and speech impairment and developmental delays. The main brain regions affected could be the prefrontal cortex (PFC) or the temporal lobe. The detrimental features could include oxidative stress, mitochondrial dysfunction, and neuroinflammation. Most often, these phenomena are interrelated and can lead to one another, creating a vicious cycle. They also influence the regulation of certain genes involved in the pathogenesis of ASD or related behavior. In the brain regions prone to these detrimental features, a cascade of free radicals, inflammatory cytokines, and mitochondrial energy disruptions is initiated. These actions during …

Sociodemographic, Neighborhood-Level, And Health-Related Factors Associated With Progression To Bariatric Surgery: A Retrospective Chart Review., Angela Godwin

Electronic Theses and Dissertations

Background: Bariatric surgery is the most effective treatment for patients with Class 3 obesity. However, of individuals who start the bariatric surgical process, only about half undergo surgery. Factors associated with completion, including race, have been described; however, consistent evidence on obstacles remains to be identified.

Objectives: To explore variables based on the Social Ecological Model (SEM) that may be related to bariatric surgery completion.

Setting: A large, private hospital with a Bariatric Center of Excellence in New York City

Methods: This retrospective chart review utilized data from adults who established an initial bariatric surgery visit from April 1, 2012, …

Microneedle-Based Lc-Ms/Ms Profiling Of Dermal Interstitial Fluid Reveals Early Lipid Dysregulation Contributing To Painful Neuropathy In Prediabetic And Type 2 Diabetic Rats, Srinivasa Rao Gadam

Biomedical Sciences ETDs

Painful diabetic neuropathy (PDN), a complication of type 1 and type 2 diabetes, also occurs in obesity and prediabetes, with dyslipidemia as a modifiable risk factor. The distal-to-proximal neuropathy pattern and length-dependent intraepidermal nerve fiber loss suggest peripheral contributions. We hypothesized that elevated neurotoxic lipid intermediates—diacylglycerols (DAG), free fatty acids (FFA), and acylcarnitines (CARs)—in the dermal interstitial fluid (ISF) drive metabolism-associated hyperalgesia in prediabetic and diabetic rats. Using a microneedle array (MIA) with LC-MS/MS, we profiled ISF and serum lipids from high-fat diet (HFD) and HFD + streptozotocin (STZ) rat models alongside Hargreaves testing. ISF lipid changes appeared earlier (weeks …

Combination Of Irreversible Electroporation And Clostridium Novyi-Nt Bacterial Therapy For Colorectal Liver Metastasis, Zigeng Zhang, Guangbo Yu, Qiaoming Hou, Farideh Amirrad, Sha Webster, Surya M. Nauli, Jianhua Yu, Vahid Yaghmai, Aydin Eresen, Zhuoli Zhang

Pharmacy Faculty Articles and Research

Colorectal liver metastasis (CRLM) poses a significant challenge in oncology due to its high incidence and poor prognosis in unresectable cases. Current treatments, including surgical resection, systemic chemotherapy, and liver-directed therapies, often fail to effectively target hypoxic tumor regions, which are inherently more resistant to these interventions. This review examines the potential of a novel therapeutic strategy combining irreversible electroporation (IRE) ablation and Clostridium novyi-nontoxic (C. novyi-NT) bacterial therapy. IRE is a non-thermal tumor ablation technique that uses high-voltage electric pulses to create permanent nanopores in cell membranes, leading to cell death while preserving surrounding structures, and …

Epigenetic Profiling Of Cell-Free Dna In Cerebrospinal Fluid: A Novel Biomarker Approach For Metabolic Brain Diseases, Kyle Sporn, Rahul Kumar, Kiran Marla, Puja Ravi, Swapna Vaja, Phani Paladugu, Nasif Zaman, Alireza Tavakkoli

SKMC Student Presentations and Publications

Due to their clinical heterogeneity, nonspecific symptoms, and the limitations of existing biomarkers and imaging modalities, metabolic brain diseases (MBDs), such as mitochondrial encephalopathies, lysosomal storage disorders, and glucose metabolism syndromes, pose significant diagnostic challenges. This review examines the growing potential of cell-free DNA (cfDNA) derived from cerebrospinal fluid (CSF) epigenetic profiling as a dynamic, cell-type-specific, minimally invasive biomarker approach for MBD diagnosis and monitoring. We review important technological platforms and their use in identifying CNS-specific DNA methylation patterns indicative of neuronal injury, neuroinflammation, and metabolic reprogramming, including cfMeDIP-seq, enzymatic methyl sequencing (EM-seq), and targeted bisulfite sequencing. By synthesizing current …

The Effect Of Oral Colchicine And Vitamin K1 On Bone Metabolism In Patients With Diabetes Mellitus: A Post-Hoc Analysis Of A 2 × 2 Factorial Randomized Controlled Trial With 18F-Sodium Fluoride Positron Emission Tomography, Jamie W. Bellinge, Marc Sim, Roslyn J. Francis, Sing Ching Lee, Dick C. Chan, Christian M. Girgis, Gerald F. Watts, Joshua R. Lewis, Carl J. Schultz

Research outputs 2022 to 2026

Purpose: Diabetes mellitus (DM) confers an increased risk of fracture. Fracture risk stratification techniques are imperfect, and preventative therapies are sparse. We aimed to describe features associated with a dysfunctional bone metabolism determined by 18F-Sodium Fluoride Positron Emission Tomography (18F-NaF PET) in patients with DM and test the effects of vitamin K1 and colchicine therapy on vertebral 18F-NaF activity. Methods: This is a post-hoc analysis of a 2 × 2 factorial randomized double-blind placebo-controlled trial. Participants aged 50–80 with DM underwent 18F-NaF PET/CT imaging at baseline, 3 months of therapy with vitamin K1 (10mg/daily) or placebo, and colchicine (0.5 mg/day) …

Clinical Outcomes After Hospitalization For Acute Coronary Syndrome In Patients Treated With Semaglutide Versus Bariatric Surgery: A Retrospective Multicenter Analysis, Nameer Ascandar, Charles Boadu, Gauthier Stepman, George Skaf, Olugbenga Oyesanmi, Sabry Omar, Rias Ali, Michael Schandorf-Lartey

HCA Healthcare Journal of Medicine

Background

Obesity is a chronic medical condition with a rising prevalence in the United States. A wide range of morbidity and mortality is associated with obesity, with coronary artery disease being among the most common. Ischemic heart disease continues to be the primary cause of death in the United States. Taken together, interventions to minimize the detrimental effects of obesity on patients at risk of heart disease will not only benefit the patient, but the health care system as well.

Methods

In this retrospective study, we used the HCA Healthcare enterprise data warehouse to identify all adult patients who were …

Intermittent Fasting For Metabolic Syndrome Management, Tony Laborde

Lynchburg Journal of Medical Science

This paper reviews the potential of intermittent fasting as a non-pharmacological therapeutic approach to the treatment of metabolic syndrome (MetS). MetS is a global health problem with risk factors that include obesity, hypertension, hyperglycemia, low high-density lipoprotein (HDL) cholesterol, and high triglycerides that predispose to cardiovascular disease and type 2 diabetes. Traditional treatment approaches, including pharmacological agents and lifestyle modification, are typically of short-term benefit. Intermittent fasting, with its scheduled cycles of eating and fasting, presents another strategy for improving weight control, insulin sensitivity, lipid profiles, and blood pressure. Various intermittent fasting regimens, including time-restricted feeding and alternate-day fasting, have …

Mechanistic Insights And Clinical Benefits Of Omega-3 Fatty Acids In Cardiovascular, Inflammatory, And Neurological Health, Anosh Tahir, Afshan Siddiq

The Thai Journal of Pharmaceutical Sciences

Background: Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are attributed with the capacity to prevent cardiovascular diseases (CVD), chronic inflammation, and neurodegenerative diseases. Their bioactive contribution consists on interfering with lipid metabolism, decreasing inflammation, and increasing neuroprotection. Still, the findings imply that there is a considerable need for greater clarification of their mechanisms and their application to clinical care.

Objectives: This narrative review is intended to discuss the potential target(s) of action, uses, and efficacy of ω-3 PUFAs in the context of CVD, inflammation, and neurodegenerative diseases.

Materials and Methods: This narrative review …

Attitudes Toward Pig Islet Xenotransplantation For Type 1 Diabetes: A Scoping Review, Daniel J Hurst, Daniel Rodger, Luz A Padilla, Fernando Ovalle

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Over 8 million people globally have type 1 diabetes. Islet allotransplantation offers an alternative to insulin therapy but is constrained by donor availability. Genetically modified pig islet transplantation presents a potential solution, yet understanding stakeholder attitudes is crucial before clinical adoption.

METHODS: This scoping review followed Joanna Briggs Institute methodology and PRISMA guidelines. CINAHL, EMBASE, PubMed, PsychINFO, and SCOPUS were searched for studies examining attitudes toward pig islet xenotransplantation among patients, healthcare workers, and other stakeholders.

RESULTS: From 199 sources, 16 met eligibility criteria, spanning ten countries from 2003 to 2023. The 23,780 participants included 1,535 (6.5%) patients/family members, …

Source-Specific Nitrate And Nitrite Intake And Association With Colorectal Cancer In The Danish Diet, Cancer And Health Cohort, Dorit W. Erichsen, Nicola P. Bondonno, Pratik R. Pokharel, Susanne M. Rosthoj, Catherine P. Bondonno, Liezhou M. Zhong, Jorg Schullehner, Torben L. Sigsgaard, Peter Fjeldstad Hendriksen, Frederik Dalgaard, Ole Raaschou-Nielsen, Jonathan M. Hodgson, Christina C. Dahm, Anja Olsen, Anne Tjonneland, Cecilie Kyro

Research outputs 2022 to 2026

Introduction: Nitrate and nitrite, present in food and drinking water, may contribute to colorectal cancer (CRC) through the formation of carcinogenic N-nitroso compounds (NOCs). This study examined source-specific associations with CRC and subtypes, considering potential dietary and lifestyle factors that influence NOC formation. Methods: In the Danish Diet, Cancer, and Health Cohort (N=54,610), nitrate/nitrite intake was estimated from comprehensive databases and national monitoring data. Over 27 years, 2245 CRC cases (1508 colon and 737 rectal) were identified via the Danish Cancer Registry. Cox proportional hazards models adjusted for sociodemographic, diet, and lifestyle factors were used to examine associations, with stratified …

Biological Age Acceleration Associated With The Progression Trajectory Of Cardio-Renal–Metabolic Multimorbidity: A Prospective Cohort Study, Yixing Tian, Jinqi Wang, Tianyu Zhu, Xia Li, Haiping Zhang, Xiaoyu Zhao, Xinghua Yang, Yanxia Luo, Lixin Tao, Zhiyuan Wu, Xiuhua Guo

Research outputs 2022 to 2026

Objectives: Previous studies have confirmed that biological age (BA) acceleration is associated with single cardio-renal–metabolic diseases (CRMDs), typically including type 2 diabetes mellitus, cardiovascular disease, and chronic kidney disease. However, its association with progression to cardio-renal–metabolic multimorbidity (CRMM, coexistence of ≥2 CRMDs) and subsequent mortality remains unexplored. Methods: Using the multi-state model, we analyzed 278,927 UK Biobank participants free of CRMDs at baseline to investigate the association between BA acceleration—measured by phenotypic age (PhenoAge) and Klemera–Doubal method age (KDMAge)—and CRMM progression trajectory, from health to the first CRMD and then to CRMM and death. BA acceleration was the residual from …

Higher Vitamin K1 Intakes Are Associated With Lower Subclinical Atherosclerosis And Lower Risk For Atherosclerotic Vascular Disease-Related Outcomes In Older Women, Montana Dupuy, Liezhou Zhong, Simone Radavelli-Bagatini, Jack Dalla Via, Kun Zhu, Lauren C. Blekkenhorst, James Webster, Nicola P. Bondonno, Allan Linneberg, Carl Schultz, Wai Lim, Richard L. Prince, Jonathan M. Hodgson, Joshua R. Lewis, Marc Sim

Research outputs 2022 to 2026

Purpose: Vitamin K may inhibit vascular calcification, a common attribute of atherosclerotic vascular diseases (ASVDs). We examined associations between dietary vitamin K1 intakes and both subclinical atherosclerosis and ASVD events, including hospitalisations and mortality, in older women.

Methods: 1,436 community-dwelling women (mean ± SD age 75.1 ± 2.7 years) were included. Vitamin K1 intakes were calculated from a validated food frequency questionnaire at baseline (1998), utilising a region-matched vitamin K food database. Common carotid artery intima–media thickness (CCA-IMT), a measure of subclinical atherosclerosis, was measured in 2001 (n = 1,090). Differences in CCA-IMT by quartiles (Q) of vitamin K1 intake …

Implementing The Fib-4 Tool For Liver Fibrosis Screening In Diabetic Patients In Primary Care, Robert I. Montillano

Doctor of Nursing Practice Final Manuscripts

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly non-non-alcoholic fatty liver disease (NAFLD), affects over 1 in 3 adults with type 2 diabetes mellitus (T2DM) and is a leading cause of advanced liver fibrosis. Despite guideline support from the American Diabetes Association (ADA) and American Association for the Study of Liver Diseases (AASLD), screening practices remain inconsistent in primary care. The Fibrosis-4 (FIB-4) index is a validated, low-cost, noninvasive tool for fibrosis risk stratification, yet it remains underutilized despite its availability in many electronic health record (EHR) systems.

Purpose: This Doctor of Nursing Practice (DNP) evidence-based practice (EBP) project …

Chronic Inflammation: The Link Between A High Added Sugar Diet And Disease, Anna Collins

Senior Honors Theses

The modern diet includes many processed foods that contain added sugars, resulting in a significant increase in daily glucose and fructose consumption. Considering this, there is an increased effort to uncover the effects of excess sugar intake on the body’s health and metabolism. Strong evidence supports the connection between a high added sugar diet and the presence of chronic, low-grade inflammation due to cellular distress and metabolic dysfunction. Prolonged inflammatory responses are linked to tissue damage and the development of various metabolic diseases that are prevalent in modern society, such as obesity, fatty liver disease, cardiovascular disease, and type 2 …

Physiologically Based And Population Pharmacokinetic Modeling Of Midazolam In Children With Obesity Using Real-World Data, Sean Mccann, Victória E. Helfer, Stephen J. Balevic, William J. Muller, John N. Van Den Anker, Amira Al-Uzri, Marisa L. Meyer, Sarah G. Anderson, Sitora Turdalieva, Andrea N. Edginton, Daniel Gonzalez, Best Pharmaceuticals For Children Act Pediatric Trials Network Steering Committee

Department of Pediatrics Faculty Papers

Children represent a highly complex and variable population for treatment, including interindividual differences in drug dose-exposure. Midazolam has been used as a sedative for hospitalized children on- and off-label; however, factors affecting interindividual variability (IIV) in observed clearance for this population are not fully understood and can result in extreme under- or overexposure. Obesity has been described as a significant influence on midazolam in adolescents, which could potentially alter drug exposure. The goal of this study was to use two modeling strategies to evaluate dose-exposure of midazolam in children with and without obesity. Population pharmacokinetic modeling assessed whether measures of …

Rescue Of The First Mitochondrial Membrane Carrier, The Mpic, By Tat-Mediated Protein Replacement Treatment, Samar Zabit, Orly Melloul, Michal Lichtenstein, Erin L. Seifert, Haya Lorberboum-Galski

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The mitochondrial phosphate carrier (mPiC), encoded by the nuclear gene SLC25A3, is synthesized with an N-terminus mitochondrial targeting sequence (MTS), enabling its import into the mitochondria. mPiC imports inorganic phosphate (P_i) into the mitochondrial matrix for ATP production and other matrix phosphorylation reactions, as well as regulates mitochondrial Ca²⁺ uptake and buffering of matrix Ca²⁺. PiC also imports copper (Cu), crucial to COX subunit holoenzyme assembly. Variants in SLC25A3 exist and lead to mPiC deficiency (MPCD), cause a rare autosomal recessive disease with no current cure; patients with MPCD usually die within the first …

Personalizing Intermittent Fasting: The Role Of Microbiome Diversity And Fiber Intake In Shaping Health Outcomes, Jana Gjini, Robin Moore, Venkateswar Venkataraman

Rowan-Virtua Research Day

BACKGROUND: Intermittent fasting (IF) has been linked to improved metabolic health, reduced inflammation, and increased longevity in animal models. These effects are thought to be mediated through changes in the gut microbiome. Murine studies consistently show that IF enhances microbial diversity and promotes beneficial species like Lactobacillus and Bifidobacterium, improving metabolic profiles and gut barrier function. However, human studies reveal inconsistent results, suggesting that individual-level factors such as baseline microbiome composition and fiber intake may influence response to IF.

HYPOTHESIS: Baseline gut microbiome diversity and habitual dietary fiber intake modulate the metabolic and inflammatory benefits of intermittent fasting in humans. …

Septo-Optic Dysplasia And Gastroschisis: Trends In Birth Prevalence And Association With Maternal Age, David J. Cullingford, Mary B. Abraham, Aris Siafarikas, A. Marie Blackmore, Jenny Downs, Peter Jacoby, Gareth Baynam, Catherine S.Y. Choong

Research outputs 2022 to 2026

This study aims to describe the risk factors and trends in birth prevalence of septo-optic dysplasia (SOD) and gastroschisis between 1980 and 2023. This descriptive, population-based study of SOD and gastroschisis used Western Australian Register of Developmental Anomalies data from 1980 to 2023. Birth prevalence was calculated using Midwives Notification System data for all births after 20 weeks gestation. Relative risk (RR) for SOD and gastroschisis showed risk by maternal age. SOD and gastroschisis occurred in 99 and 391 cases respectively (no dual diagnoses), with a birth prevalence of 1.41 and 3.71 per 10,000 respectively (from 2010 to 2019), and …

Maternal Responsiveness To Infant Hunger Cues: Is It Possible To Mitigate Risk Of Obesity Starting In Infancy?, Arrianna A. Powers

Rowan-Virtua Research Day

Background: Childhood obesity is becoming a predominant health concern with over 37 million children under the age of 5 being overweight. Instances of rapid weight gain in infancy correlate to greater risk for obesity later on in life.

Methods: This study aimed to look at feeding modality and style for their impact on maternal responsiveness to infant hunger cues and RWG. A database search identified 21 studies eligible to be included in the review out of 150.

Discussion: Key findings showed breast-feeding mothers were most responsive to hunger cues, breastfed infants expressed greater cues than their formula-fed peers, and responsive …