Digital Commons Network^™

The Advancement And Utility Of Multimodal Imaging In The Diagnosis Of Degenerative Disc Disease, Eric M. Teichner, Robert C. Subtirelu, Connor R. Crutchfield, Chitra Parikh, Arjun Ashok, Sahithi Talasila, Victoria Anderson, Milan Patel, Sricharvi Mannam, Andrew Lee, Thomas Werner, William Y. Raynor, Abass Alavi, Mona-Elisabeth Revheim

SKMC Student Presentations and Publications

Degenerative disc disease (DDD) is a common spinal condition characterized by the deterioration of intervertebral discs, leading to chronic back pain and reduced mobility. While magnetic resonance imaging (MRI) has long been the standard for late-stage DDD diagnosis, its limitations in early-stage detection prompt the exploration of advanced imaging methods. Positron emission tomography/computed tomography (PET/CT) using ¹⁸F- fluorodeoxyglucose (FDG) and ¹⁸F-sodium fluoride (NaF) has shown promise in identifying metabolic imbalances and age-related spinal degeneration, thereby complementing CT grading of the disease. The novel hybrid imaging modality PET/MRI provides new opportunities and are briefly discussed. The complex pathophysiology of …

Factors Driving Adolescent Tuberculosis Incidence By Age And Sex In 30 High-Tuberculosis Burden Countries: A Mathematical Modelling Study, Silvia S Chiang, Megan B Murray, Alexander W Kay, Peter J Dodd

Faculty, Staff and Students Publications

INTRODUCTION: During adolescence, tuberculosis incidence rises, with a greater increase in males compared with females. Tuberculosis notifications and estimates infrequently disaggregate adolescent age groups. Moreover, the factors that drive the increases in overall incidence and the male-to-female (MF) ratio remain unclear.

METHODS: We constructed a mechanistic model to estimate cumulative Mycobacterium tuberculosis infection and tuberculosis disease incidence in the WHO’s 30 high-tuberculosis burden countries (HBCs), which represent 86%–90% of global tuberculosis incidence. We derived infection risk from tuberculosis prevalence and assortative social mixing based on sex and age (10–14 years vs 15–19 years old). We adjusted age subgroup-specific risks of …

Photoacoustic Imaging For Image-Guided Gastric Tube Placement: Ex Vivo Characterization, Samuel John, Yeidi Yuja Vaquiz, Nikhila Nyayapathi, Loay Kabbani, Anoop Nilam, Jonathan F Lovell, Nicole A Wilson, Yan Yan, Mohammad Mehrmohammadi

Faculty, Staff and Student Publications

Over 250,000 gastrostomy tubes (G-tubes) are placed annually in the United States. Percutaneous endoscopic gastrostomy (PEG) is the most widely used clinical method for placing G-tubes within the stomach. However, endoscope detectability is limited due to the scattering of light by tissues. Poor organ visibility and low sensitivity of the palpation techniques cause blind needle insertions, which cause colon/liver perforations, abdominal bleeding, and gastric resections. Additionally, imaging artifacts and the poor distinguishability between water-filled tissues make ultrasound (US) imaging-based techniques incompatible with G-tube placement. The risk of ionizing radiation exposure and the confinement of fluoroscopy to radiology suites limits its …

Impact Of Diabetes On Fall Related Lower Limb Fractures, Bryce M. Bellon, Daniel Salinas, Patrick De La Torre Shutz, Hunter Butler, Sean Corcoran, Kelsey Baker

Research Symposium

Background: Diabetes is a disorder that affects many Americans, characterized primarily by hyperglycemia due to either insulin resistance or lack of insulin secretion. This condition not only impacts blood sugar levels but also has significant effects on bone health. In diabetes, bone density is often decreased due to reduced osteoblast activity, which is responsible for bone formation, and increased osteoclast activity, which leads to bone resorption. This imbalance accelerates the breakdown of bone. Additionally, diabetics frequently suffer from lower extremity arterial disease (LEAD), which results in poor vascularization of the lower limbs. These factors contribute to an increased risk of …

Markers Of Growth And Nutrition In Children With Acquired Chylothorax Post Chd Surgery, Kevin N. Marzotto, Karin R. Videlefsky, Meghan P. Howell, Thomas R. Kimball, Frank A. Pigula, Kurt D. Piggott

School of Medicine Faculty Publications

Background: Acquired chylothorax is an established complication of CHD surgery, affecting 2-9% of patients. CHD places a child at risk for failure to thrive, with subsequent chylothorax imposing additional risk. Objective: We conducted a retrospective chart review to ascertain quantitative markers of nutrition and growth in children affected by chylothorax following CHD surgery between 2018 and 2022 compared to controls. Methods: We utilised electronic medical record system, EPIC, at Children's Hospital, New Orleans, targeting subjects < 18 years old who underwent CHD surgery between 2018 and 2022 and developed a subsequent chylothorax. Study subjects were identified using the 10th revision of the International Classification of Diseases codes (ICD-10 codes: J94.0, I89.8, and J90.0). Each chylothorax case (n = 20) was matched by procedure type and age to a control with no chylothorax (n = 20). Data were recorded in REDCap and analysed using SPSS. Results: After removal of outliers, we analysed 19 total matched pairs. There was no statistical difference in growth velocity (p = 0.12), weight change (operation to discharge) (p = 0.95), weight change (admission to discharge) (p = 0.35), Z-score change (operation to discharge) (p = 0.90), Z-score change (admission to discharge) (p = 0.21), serum protein (p = 0.88), or serum albumin (p = 0.82). Among cases, linear regression demonstrated no significant association between maximum chylous output and growth velocity (p = 0.91), weight change (operation to discharge) (p = 0.15), or weight change (admission to discharge) (p = 0.98). Conclusions: We did not observe statistically significant markers of growth or nutrition in children with chylothorax post-CHD surgery compared to those without chylothorax. Multisite data collection and analysis is required to better ascertain clinical impact and guide clinical practice.

Epigenetic Landscapes Of Aging In Breast Cancer Survivors: Unraveling The Impact Of Therapeutic Interventions-A Scoping Review, Nikita Nikita, Zhengyang Sun, Swapnil Sharma, Amy L Shaver, Victoria Seewaldt, Grace Lu-Yao

Department of Medical Oncology Faculty Papers

Breast cancer therapies have dramatically improved survival rates, but their long-term effects, especially on aging survivors, need careful consideration. This review delves into how breast cancer treatments and aging intersect, focusing on the epigenetic changes triggered by chemotherapy, radiation, hormonal treatments, and targeted therapies. Treatments can speed up biological aging by altering DNA methylation, histone modifications, and chromatin remodeling, affecting gene expression without changing the DNA sequence itself. The review explains the double-edged sword effect of therapy-induced epigenetic modifications, which help fight cancer but also accelerate aging. Chemotherapy and targeted therapies, in particular, impact DNA methylation and histone modifications, promoting …

Pleural Effusion: Shedding Light On Pleural Disease Beyond Infection And Malignancy, William C Harding, Abdul R Halawa, Mazen M Aiche, Bilal Zafar, Hyeon-Ju R Ali, Lara Bashoura, Saadia A Faiz

Faculty, Staff and Student Publications

Background and Objectives: Non-malignant pleural effusions (NMPEs) are the most frequently encountered pleural disease. They arise from various non-malignant, non-infectious clinical conditions, including cardiac, renal, and hepatic organ dysfunction. Despite their wide prevalence, there is a lack of literature for NMPE. This publication aims to provide an updated overview of the causes, diagnostic strategies, and management options for NMPE.

Materials and Methods: This review synthesizes findings from studies published on NMPE, focusing on the presentation, diagnosis (such as imaging and pleural fluid analysis), and management strategies. Studies were selected based on relevance and were analyzed to provide a comprehensive summary …

Somatic Acupressure For The Management Of The Fatigue-Sleep Disturbance-Depression Symptom Cluster In Breast Cancer Survivors: A Study Protocol For A Phase Iii Randomised Controlled Trial, Mengyuan Li, Tao Wang, Xian Liang Liu, Ren Li Deng, Wai Hang Kwok, Li Qun Yao, Jing Yu Benjamin Tan

Research outputs 2022 to 2026

Introduction The fatigue-sleep disturbance-depression symptom cluster (FSDSC) is commonly experienced by breast cancer (BC) survivors, leading to a deteriorated quality of life (QoL). Somatic acupressure (SA) has been recommended as a promising non-pharmacological intervention for cancer-related fatigue (the core symptom of the FSDSC) in the guidelines, showing its encouraging role in relieving cancer-related sleep disorders, fatigue and depression. This phase III randomised controlled trial (RCT) is designed to evaluate the effects, safety and cost-effectiveness of SA for managing the FSDSC in BC survivors. Methods This phase III RCT will be a partial-blinded, sham-controlled, three-arm, parallel clinical trial, involving a 7-week …

Evaluating The Effect Of Consumption Of Fermented Foods On Glycemic Control And Markers Of Cardiometabolic Risk Amongst Pre-Diabetic And Type 2 Diabetes Mellitus Adult Patients: A Systematic Review And Meta-Analysis, Alex Makau Muia

Master of Medicine in Family Medicine

Introduction 

Type 2 diabetes mellitus (T2DM) remains a major global health challenge, particularly in resource limited countries where conventional treatments are often inaccessible or unaffordable. While lifestyle interventions can reduce diabetes risk, their efficacy is moderate, highlighting the need for alternative strategies. Fermented foods (FFs), which are widely available and affordable, have been shown to improve glucose metabolism and may offer a promising adjunct in the prevention and management of T2DM and prediabetes.

Methods 

A systematic review and meta-analysis were conducted to assess the effects of fermented food consumption on glycemic control and cardiometabolic risk markers in adults with prediabetes …

Neurocognitive Gains Among Ugandan Children With Sickle Cell Anemia On Hydroxyurea: 18-Month Trial Interim Results, Shubaya Kasule Naggayi, Dennis Kalibbala, Vincent Mboizi, John M. Ssenkusu, Zhezhen Jin, Caterina Rosano, Deogratias Munube, Bill Wambaka, Ruth Namazzi, Robert Opoka

Paediatrics and Child Health, East Africa

Children with sickle cell anemia (SCA) frequently develop progressive neurocognitive impairment. We aimed to determine effects of hydroxyurea therapy on neurocognitive function in Ugandan children with SCA by comparing levels at enrollment to a planned 18-month interim assessment. Ugandan children (N=264) ages 3-9 years were enrolled from a SCA clinic and treated in a 30-month singlearm open-label trial with escalation to maximum tolerated dose (MTD). Primary outcome was the effects of hydroxyurea on cognition, attention and executive function, along with transcranial doppler ultrasound (TCD) blood flow velocity. Sibling controls (N=110) without SCA underwent neurocognitive testing in parallel to establish age-normalized …

A Preliminary Report Of The Carotenoid Assessment In Adults 50 Years Of Age And Older In Louisiana, Mary-Catherine Feazell

Master's Theses

Fruits and vegetables are at the core of a healthy, balanced diet. They assist in preventing the development of chronic diseases such as hypertension, diabetes, cardiovascular disease, and cancer (Fadnes, et al., 2022). Aging is a natural biological process followed by disease, cognitive impairment, and a natural decline of the body’s ability to perform at its best. The older adult population is currently the fastest-growing population globally (El-Shebiney et al., 2022). Vitamin A is crucial for several parts of the body to function correctly. Despite the positive effects of Vitamin A on the body, the recommended dietary intake is not …

Engineering A Novel Treg Population To Control Autoimmune Diabetes, Sofia Colon Guzman, Elly Puckett, Ryan T. Fischer, Mary Markiewicz

Posters

Purpose Type 1 diabetes (T1D) in an autoimmune disorder where T cells attack  islet cells, which are the pancreatic cells responsible for insulin production. T1D affects about 1 in 500 children in the United States and is one of the most common chronic diseases in pediatrics. Currently, insulin is the most effective treatment for T1D However, it does not change the underlying disease, and patients still experience many complications throughout their lifetimes. With a significant increase in the prevalence of T1D in children and adolescence in the past two decades, it’s important to explore therapies that alter the immune …

The Efficacy Of The Minimally Invasive Lumbar Decompression (Mild®) Procedure: A Prisma-Compliant Systemic Review And Meta-Analysis, Xin-Yu Zhang, Jian-Li Zhao, Ya-Jing Wang, Jie Luan, Hong-Qi Lin, Dajie Wang

Department of Anesthesiology Faculty Papers

BACKGROUND: Lumbar spinal stenosis is the most common cause for spinal surgery of older adults. It is associated with pain in the legs and back as well as impaired ambulation. Minimally Invasive Lumbar Decompression (MILD®, Vertos Medical) is a percutaneous, image-guided lumbar decompression technique for central canal stenosis secondary to a hypertrophied ligamentum flavum. However, whether MILD can achieve adequate beneficial results in patients with lumbar spinal stenosis remains undetermined.

OBJECTIVE: To assess the efficacy and complications of MILD for lumbar spinal stenosis.

STUDY DESIGN: A systematic review and meta-analysis.

METHODS: Electronic databases were searched to identify all clinical trials …

Early Diet Liberalization After Anterior Lumbar Interbody Fusion Improves Postoperative Recovery, Tiffany Bridges, Matthew Meade, Parker L. Brush, Yunsoo Lee, Rajkishen Narayanan, Michael A. Mccurdy, Mark J. Lambrechts, Alex Charlton, Eleanor Jenkins, Robert Juniewicz, Henson Destine, I. David Kaye, Mark Kurd, Jose A. Canseco, Alan S. Hilibrand, Alex R. Vaccaro, Gregory D. Schroeder, Christopher K. Kepler

Department of Orthopaedic Surgery Faculty Papers

STUDY DESIGN: Retrospective Cohort Study.

OBJECTIVES: The objective of this study was to assess the impact of diet liberalization on short-term outcomes in patients undergoing anterior interbody lumbar fusion (ALIF).

METHODS: A retrospective review was performed for patients undergoing ALIF at our tertiary care center institution from 2010 to 2022. Electronic medical records were reviewed for demographics, surgical characteristics, and 90-day postoperative outcomes.

RESULTS: We included 515 patients in this study with 102 patients receiving a full diet on the same day as their operation. All other patients had a delay of at least 1 day (average 1.6 days) until …

Correlation Between Fetal Abdominal Wall Adiposity And Neonatal Outcomes, Elaine Murugi Nyaga

Master of Medicine in Obstetrics and Gynecology

BACKGROUND 

Fetal growth is a result of complex interactions between genetic, nutritional, environmental, uteroplacental, and fetal factors which impact on delivery and subsequent neonatal outcomes. Fetal abdominal adiposity serves as an important indicator of fetal growth and body composition. While gestational diabetes mellitus (GDM) can influence fetal fat deposition, understanding how adiposity correlates with birth weight and neonatal outcomes in both GDM and non-GDM pregnancies provides insight into the broader significance of fetal adiposity as a marker of fetal health.

Methodology 

A cross-sectional study was conducted on 269 pregnant women to examine fetal abdominal adiposity, measured as fetal abdominal subcutaneous …

Cinacalcet For Infants And Young Children On Maintenance Dialysis: Determining The Right Time, The Right Dose And The Right Patients., Kyle Ying-Kit Lin, Fiona Fung-Yee Lai, Eugene Yu-Hin Chan, Bradley A. Warady

Manuscripts, Articles, Book Chapters and Other Papers

Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD) is a recognized complication of kidney failure, which can lead to short stature, bone deformity, slipped capital femoral epiphysis, and bone fracture in children. Despite the use of conventional therapies, a subgroup of patients receiving dialysis continues to experience secondary or even tertiary hyperparathyroidism. Cinacalcet, a calcimimetic agent, has been shown to be a promising therapeutic option to control hyperparathyroidism with reasonable safety profiles in adults and older children. Nevertheless, there is a paucity of data and guidance pertaining to its use among the younger children on dialysis, who are often the …

Massive Gastroduodenal Trichobezoar Removed With Hydrodissection: A Case Report, Seth Saylors, Cory Nonnemacher, Irene Isabel P. Lim

Manuscripts, Articles, Book Chapters and Other Papers

Introduction

Case presentation

The Clinical Phenotype Of Motor Neurone Disease In A Kenyan Hospital – Based Population, Effie Nailah Kamadi

Master of Medicine in Internal Medicine

Introduction: Motor Neurone Disease (MND) is a rare, disabling and incurable illness marked by relentless degeneration of motor neurons with loss of voluntary motor function and eventual death. In the West, patient demographics and clinical characteristics are well documented. Available African research is mostly for North, West and South Africa with a knowledge gap existing on the East African illness. This study characterized MND phenotype in a Kenyan population.

Objectives: To describe the clinical phenotype and outcomes of MND in a Kenyan hospital-based population.

Methods: The medical charts of all adult MND patients assessed at AKUHN between …

The Prevalence And The Predictors Of Diabetes Distress In Patients With Type 2 Diabetes Attending Diabetes Clinics At A Tertiary Private Hospital In Nairobi, Kenya., Soulthy Azamkhan Mohamed

Master of Medicine in Family Medicine

Background Diabetes distress encompasses a spectrum of emotional and psychological challenges faced by individuals managing diabetes, including anxiety, stress, depression, frustration, and feelings of helplessness. This distress arises from the constant demands of monitoring blood sugar levels, managing medications, adhering to dietary restrictions, engaging in regular physical activity, and navigating potential complications. Social and emotional factors such as stigma, discrimination, and concerns about future health further contribute to this burden. Factors like fear of hypoglycemia, financial strain, fluctuating blood sugar levels, anxiety about complications, and impacts on personal relationships exacerbate diabetes distress. Left unaddressed, diabetes distress can lead to poor …

Dementia In A Resource-Constrained Sub-Saharan African Setting: A Comprehensive Retrospective Analysis Of Prevalence, Risk Factors, And Management At The Only Neuropsychiatric Facility In Northeastern Nigeria, Ibrahim Abdu Wakawa, Umar Baba Musami, Suleiman Hamidu Kwairanga, Placidus Nwankuba Ogualili, Mohammed Yusuf Mahmood, Muhammad Abba Fugu, Mohammed Mala Gimba, Muktar Mohammed Allamin, Zaharadeen Umar Abbas, Chinedu Momoh

Brain and Mind Institute

INTRODUCTION: Dementia prevalence is increasing in sub-Saharan Africa, poten-tially due to population growth and aging. Resource-constrained settings such asNortheastern Nigeria face challenges in dementia management.

METHODS: We assessed dementia burden and management at the Federal Neuropsy-chiatric Hospital Maiduguri, the only neuropsychiatric facility in Northeastern Nigeria.This retrospective analysis included patient records from 1999 to 2023 for individuals60 year of age and older with a dementia diagnosis.

RESULTS: Of the 1216 cases reported, Alzheimer’s disease (60.5%) was the mostcommon subtype, followed by vascular dementia (24.5%). Hypertension (41.6%) wasthe most frequent comorbidity. Memory loss was present in all cases, whereasbehavioral …

Evaluating Dysphagia Duration And Severity After Acdf In Patients With Underlying Dysphagia - A Prospective, Multicenter Study, Aditya Mazmudar, Taylor Paziuk, Khoa Tran, Tyler Henry, Samuel Oh, Caroline Purtill, Daniel Habbal, Goutham Yalla, Quinlin Harrill, Brandon Sherrod, Erica Bisson, Darrel Brodke, Christopher Kepler, Gregory Schroeder, Alex Vaccaro, Alan Hilibrand, Jeffrey Rihn

Department of Orthopaedic Surgery Faculty Papers

STUDY DESIGN: Prospective Cohort Study.

OBJECTIVES: The purpose of this study was to prospectively evaluate the impact of preoperative dysphagia on the postoperative incidence and severity of dysphagia in patients undergoing ACDF at multiple institutions.

METHODS: After IRB approval, patients over 18 years of age who underwent an elective ACDF for degenerative conditions were prospectively enrolled at two academic centers from 2018 to 2021. Preoperative dysphagia was self-reported by patients through a pre-operative questionnaire on a binary basis. Patients completed dysphagia surveys (Bazaz, Dysphagia Short Questionnaire, 10-item Eating Assessment Tool) to assess dysphagia severity during their preoperative visit, and these …

A Study Of Secondary Traumatic Stress In Health Care Professionals In Long-Term Care., Bethany Proudfoot

Doctor of Social Work Capstone Projects

Secondary traumatic stress (STS) is a significant concern for healthcare professionals in long-term care (LTC) settings. This study explores the impact of STS on clinical staff, addressing the research question: How has STS affected employees within the LTC sector, and what resources or support can be provided to mitigate its effects? The study utilized a mixed-methods approach, combining survey data from clinical staff across five LTC facilities in Ohio, incorporating the survey data measuring levels of STS and qualitative responses. Findings revealed that 64% of participants experienced high to severe levels of STS, with symptoms including anxiety, depression, sleep disturbances, …

Insulin Receptor Responsiveness Governs Tgfβ-Induced Hepatic Stellate Cell Activation: Insulin Resistance Instigates Liver Fibrosis, Wang-Hsin Lee, Evelyn A. Bates, Zachary A. Kipp, Sally Pauss, Genesee J. Martinez, Cheavar A. Blair, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

The insulin receptor (INSR) has been shown to be hyperactive in hepatic stellate cells (HSCs) in humans and rodents with liver fibrosis. To explore HSC cellular mechanisms that INSR regulates during pro-fibrotic stimulation, we used CRISPR-Cas9 technology. We knocked out a portion of the INSR gene in human LX2 HSC cells (INSRe5- 8 KO) that regulates insulin responsiveness but not the insulin-like growth factor (IGF) or transforming growth factor-β (TGFβ) signaling. The INSRe5- 8 KO HSCs had significantly higher cell growth, BrdU incorporation, and lower TP53 expression that suppresses growth, and they also exhibited increased migration compared to the Scramble …

Exploring Oxylipins In Host–Microbe Interactions And Their Impact On Infection And Immunity, Robert J. Neff, Christopher D. Radka

Markey Cancer Center Faculty Publications

Plasma lipids are essential components of biological systems, transported through interactions with proteins to maintain cellular functions. These lipids exist in various forms, such as fatty acids, glycerolipids, glycerophospholipids, sphingolipids, sterols, and prenol lipids, derived from dietary intake, adipose tissue, and biosynthesis. While the association between certain fatty acids and cardiovascular diseases has been widely recognized, polyunsaturated fatty acids (PUFAs) exhibit cardioprotective effects, reducing risks of arrhythmias and heart-related mortality. This is due to their role in the production of eicosanoids, which modulate inflammation. Chronic inflammation, particularly in obesity, is significantly influenced by fatty acids, with saturated fatty acids promoting …

Rising Mortality Rates Linked To Type-2 Diabetes And Obesity In The United States: An Observational Analysis From 1999 To 2022, Mushood Ahmed, Abdullah Nofal, Aimen Shafiq, Hira Javaid, Areeba Ahsan, Zain Ali Nadeem, Raheel Ahmed, Mahboob Alam, Mamas A Mamas, Marat Fudim, Gregg C Fonarow

Faculty, Staff and Students Publications

Background: The prevalence of type 2 diabetes (T2D) and obesity are increasing in the United States. However, population-level data for mortality trends due to T2D and obesity are limited. This study aims to assess these death trends among adults in the United States categorized by sex, race, and geographical location.

Methods: We queried the CDC-WONDER database for multiple cause of death data of adults aged ≥25 years. The crude mortality rates (CMR), age-adjusted mortality rates (AAMRs), annual percent change (APC), and the average APC (AAPC) along with a 95% confidence interval (CI) were analyzed.

Results: From 1999 to 2022, a …

Exploration Of Cytokines And Microbiome Among Males And Females With Diarrhea-Predominant Irritable Bowel Syndrome, Li Juen Chen, Anna M Plantinga, Robert Burr, Kevin Cain, Pamela Barney, Tor Savidge, Robert J Shulman, Margaret Heitkemper, Kendra Kamp

Faculty, Staff and Students Publications

Background: Whether pathophysiological factors differ between males and females with irritable bowel syndrome-diarrhea (IBS-D) remains to be tested. To better understand potential sex differences, males with IBS-D were compared to naturally cycling females and to females with IBS-D taking hormonal contraception on plasma levels of cytokines and gut microbiome characteristics.

Methods: Males and females with Rome III IBS-D completed questionnaires and kept a daily symptom diary for 28 days. Blood and stool samples were collected between days 3 and 8 of the daily diary (estrogen-dominant days in naturally cycling females). Blood samples were analyzed for lipopolysaccharide (LPS)-stimulated and unstimulated cytokine …

Early Life Epigenetics And Childhood Outcomes: A Scoping Review, Srirupa Hari Gopal, Theresa Alenghat, Mohan Pammi

Faculty, Staff and Students Publications

Epigenetics is the study of changes in gene expression, without a change in the DNA sequence that are potentially heritable. Epigenetic mechanisms such as DNA methylation, histone modifications, and small non-coding RNA (sncRNA) changes have been studied in various childhood disorders. Causal links to maternal health and toxin exposures can introduce epigenetic modifications to the fetal DNA, which can be detected in the cord blood. Cord blood epigenetic modifications provide evidence of in-utero stressors and immediate postnatal changes, which can impact both short and long-term outcomes in children. The mechanisms of these epigenetic changes can be leveraged for prevention, early …

Safety And Efficacy Of Dtx401, An Aav8-Mediated Liver-Directed Gene Therapy, In Adults With Glycogen Storage Disease Type I A (Gsdia), David A Weinstein, Terry G Derks, David F Rodriguez-Buritica, Ayesha Ahmad, María-Luz Couce, John J Mitchell, Rebecca Riba-Wolman, Malaya Mount, Julieta Bonvin Sallago, Katalin M Ross, Melanie M Van Der Klauw, Foekje De Boer, Caroline Van Der Schaaf, Heather Saavedra, Miguel Martínez-Olmos, Elvis Atanga, Asad Hosseini, Deepali Mitragotri, Eric Crombez

Faculty, Staff and Student Publications

Glycogen storage disease type Ia (GSDIa) is a rare, life‐threatening, inherited carbohydrate metabolism disorder caused by glucose‐6‐phosphatase (G6Pase) deficiency, which is essential for glycogenolysis and gluconeogenesis. GSDIa management includes a strict medically prescribed diet that typically includes daily uncooked cornstarch doses, including overnight, to maintain euglycemia. DTX401 is an investigational adeno‐associated virus serotype 8 vector expressing the human G6PC1 gene that encodes G6Pase. This open‐label, phase 1/2, dose‐escalation, 52‐week gene therapy trial evaluated the safety and efficacy of a single DTX401 infusion in 12 adults with GSDIa (ClinicalTrials.gov Identifier: NCT03517085). Three participants in Cohort 1 received DTX401 2.0 × …

Oxidized Carbon Nanoparticles Enhance Cellular Energetics With Application To Injured Brain, Karthik Mouli, Anton V Liopo, Emily A Mchugh, Erica Underwood, Jing Zhao, Pramod K Dash, Anh T T Vo, Vikas H Malojirao, Muralidhar L Hegde, James M Tour, Paul J Derry, Thomas A Kent

Faculty, Staff and Student Publications

Pro-energetic effects of functionalized, oxidized carbon nanozymes (OCNs) are reported. OCNs, derived from harsh acid oxidation of single-wall carbon nanotubes or activated charcoal are previously shown to possess multiple nanozymatic activities including mimicking superoxide dismutase and catalyzing the oxidation of reduced nicotinamide adenine dinucleotide (NADH) to NAD+. These actions are predicted to generate a glycolytic shift and enhance mitochondrial energetics under impaired conditions. Impaired mitochondrial energy metabolism is increasingly recognized as an important facet of traumatic brain injury (TBI) pathophysiology and decreases the efficiency of electron transport chain (ETC)-coupled adenosine triphosphate (ATP) and NAD+ regeneration. In vitro, OCNs promote a …

Safety And Antitumor Activity Of A Novel Acd25 Treg Depleter Rg6292 As A Single Agent And In Combination With Atezolizumab In Patients With Solid Tumors, Valentina Gambardella, Michael Ong, Maria E Rodriguez-Ruiz, Jean-Pascal Machiels, Miguel F Sanmamed, Vladimir Galvao, Anna Spreafico, Daniel J Renouf, Stephen J Luen, Rachel Galot, Bernard Doger De Spéville, Emiliano Calvo, Aung Naing, Samira Curdt, Theresa Maria Kolben, Eva Rossmann, Tamara Tanos, Kevin Smart, Maria Amann, Yuying Xie, Linxinyu Xu, Enrique Gomez Alcaide, Nicolas Städler, Nicole Justies, Christophe Boetsch, Vaios Karanikas, Gabriel Schnetzler, Kristoffer S Rohrberg

Faculty, Staff and Student Publications

Purpose: Therapeutic depletion of immunosuppressive regulatory T cells (Treg) may overcome resistance to cancer immunotherapies. RG6292 is an anti-CD25 antibody that preferentially depletes Tregs while preserving effector T-cell functions in preclinical models. The safety, pharmacokinetics, pharmacodynamics, and antitumor efficacy of selective Treg depletion by RG6292 administered as monotherapy or in combination with atezolizumab were evaluated in two phase I studies.

Patients and methods: Adult patients with advanced solid tumors were administered intravenous RG6292, given every 3 weeks alone (study 1: NCT04158583, n = 76) or with 1,200 mg atezolizumab every 3 weeks (study 2: NCT04642365, n = 49). …