Diseases Commons^™

Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Premranjan Kumar, Chun Liu, James Suliburk, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar

Faculty, Staff and Students Publications

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.

METHODS: Twenty-four …

Interfering With Lipid Metabolism Through Targeting Ces1 Sensitizes Hepatocellular Carcinoma For Chemotherapy, Gang Li, Xin Li, Iqbal Mahmud, Jazmin Ysaguirre, Baharan Fekry, Shuyue Wang, Bo Wei, Kristin L Eckel-Mahan, Philip L Lorenzi, Richard Lehner, Kai Sun

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC) is the most common lethal form of liver cancer. Apart from surgical removal and transplantation, other treatments have not yet been well established for patients with HCC. In this study, we found that carboxylesterase 1 (CES1) is expressed at various levels in HCC. We further revealed that blockage of CES1 by pharmacological and genetical approaches leads to altered lipid profiles that are directly linked to impaired mitochondrial function. Mechanistically, lipidomic analyses indicated that lipid signaling molecules, including polyunsaturated fatty acids (PUFAs), which activate PPARα/γ, were dramatically reduced upon CES1 inhibition. As a result, the expression of SCD, …

Impact Of Perioperative Dexamethasone On Hospital Length Of Stay And Glycemic Control In Patients With Type 2 Diabetes Undergoing Total Hip Arthroplasty, Vanessa Williams, Mohammad J. Uddin Ansari, Amruta Jaju, Stacey Ward, Daniel O'Keefe, Jumana Abdelkarim, Nicole Montes, Ula Tarabichi, Albert Botchway, Michael G. Jakoby Iv

Journal of Patient-Centered Research and Reviews

Purpose: This study aimed to evaluate effects of perioperative dexamethasone on hospital length of stay (LOS) and glycemic control for patients with type 2 diabetes mellitus undergoing total hip arthroplasty (THA).

Methods: We performed retrospective case review of THA performed in adults (≥ 18 years old) with type 2 diabetes at Springfield Memorial Hospital (Springfield, IL) immediately before (2013), during (2014), and after (2015) publication of consensus guidelines for use of perioperative dexamethasone. Hospital LOS was the primary endpoint. Capillary blood glucose by hospital day, proportion of patients treated with insulin, and median insulin dose by hospital day …

Evaluating The Association Between Depressive Symptoms And Glycemic Control Among Residents Of Rural Appalachia, Brittany L. Smalls, Adebola Adegboyega, Ellen Combs, Eli W. Travis, Felipe De La Barra, Lovoria B. Williams, Nancy Schoenberg

Journal of Appalachian Health

Introduction: Type 2 diabetes mellitus (T2DM) is associated with a range of co-morbid physical and psychological conditions, including depression. Yet there is a dearth of evidence regarding the prevalence of depression among those in Appalachia living with T2DM; this gap persists despite the higher regional prevalence of T2DM and challenging social determinants of health.

Purpose: This study aimed to provide greater detail about the relationships between T2DM and depressive symptoms in adults living in Appalachia Kentucky.

Methods: The present study was a cross-sectional analysis of baseline data derived from an ongoing study of Appalachia Kentucky adults living with T2DM. Outcome …

Adar1 Deletion Causes Degeneration Of The Exocrine Pancreas Via Mavs-Dependent Interferon Signaling, Dhwani N Rupani, Fredrik I Thege, Vidhi Chandra, Hajar Rajaei, Robert W Cowan, Sonja M Wörmann, Olivereen Le Roux, Prerna Malaney, Sara L Manning, Jack Hashem, Jennifer Bailey-Lundberg, Andrew D Rhim, Florencia Mcallister

Faculty, Staff and Student Publications

Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA-binding protein that deaminates adenosine (A) to inosine (I). A-to-I editing alters post-transcriptional RNA processing, making ADAR1 a crucial regulator of gene expression. Consequently, Adar1 has been implicated in organogenesis. To determine the role of Adar1 in pancreatic development and homeostasis, we conditionally deleted Adar1 from the murine pancreas (Ptf1aCre/+; Adar1Fl/Fl). The resulting mice had stunted growth, likely due to malabsorption associated with exocrine pancreatic insufficiency. Analyses of pancreata revealed ductal cell expansion, heightened interferon-stimulated gene expression and an increased influx of immune cells. Concurrent deletion of Adar1 and Mavs, a …

Bcl2l11 Induction Mediates Sensitivity To Src And Mek1/2 Inhibition In Thyroid Cancer, Madison M Rose, Veronica L Espinoza, Katelyn J Hoff, Laura A Pike, Vibha Sharma, Marie-Claude Hofmann, Aik Choon Tan, Nikita Pozdeyev, Rebecca E Schweppe

Faculty, Staff and Student Publications

Patients with advanced thyroid cancer, including advanced papillary thyroid cancer and anaplastic thyroid cancer (ATC), have low survival rates because of the lack of efficient therapies available that can combat their aggressiveness. A total of 90% of thyroid cancers have identifiable driver mutations, which often are components of the MAPK pathway, including BRAF, RAS, and RET-fusions. In addition, Src is a non-receptor tyrosine kinase that is overexpressed and activated in thyroid cancer, which we and others have shown is a clinically relevant target. We have previously demonstrated that combined inhibition of Src with dasatinib and the MAPK …

Qualitative Study Of Pathways To Care Among Adults With Diabetes In Rural Guatemala, Anita Nandkumar Chary, Meghna Nandi, David Flood, Scott Tschida, Katharine Wilcox, Sophie Kurschner, Pablo Garcia, Peter Rohloff

Faculty, Staff and Students Publications

OBJECTIVE: The burden of diabetes mellitus is increasing in low-income and middle-income countries (LMICs). Few studies have explored pathways to care among individuals with diabetes in LMICs. This study evaluates care trajectories among adults with diabetes in rural Guatemala.

DESIGN: A qualitative investigation was conducted as part of a population-based study assessing incidence and risk factors for chronic kidney disease in two rural sites in Guatemala. A random sample of 807 individuals had haemoglobin A1c (HbA1c) screening for diabetes in both sites. Based on results from the first 6 months of the population study, semistructured interviews were performed with 29 …

Standardized Training To Improve The Quality Of Screening Diabetic And Hypertension-Related Opthalmoscopic Exams, Ashley Faye, Pradeep D'Souza, Elizabeth Suniega

Gulf Coast Division GME Research Day 2023

No abstract provided.

Invasive Testing For Pre-Operative Localization Of Parathyroid Tumors, Akua Graf, Craig Cochran, Samira Sadowski, Naris Nilubol, William F. Simonds, Lee S. Weinstein, Richard Chang, Smita Jha

East Florida Division GME Research Day 2023

Context: The identification of parathyroid tumor(s) in patients with persistent/recurrent primary hyperparathyroidism (PHPT) is critical for a successful re-operative surgery. If non-invasive studies (ultrasound, CT, MRI, sestamibi) fail to conclusively localize the tumor, invasive procedures (arteriography and selective venous sampling) are performed.

Objective: To describe our experience with invasive studies for parathyroid tumor localization and provide follow-up data on selective arterial hypocalcemic stimulation with central venous sampling, a technique developed at our center.

Methods: We identified patients who underwent preoperative invasive testing for localization of parathyroid tumor from 1991-2020. The result of each invasive localization study (arteriogram, hypocalcemic stimulation and …

Unmasking The Cause: A Case Of Adrenal Insufficiency Masquerading As Insulinoma-Induced Hypoglycemia, Michael C. Miley

West Florida Division GME Research Day 2023

No abstract provided.

Late Onset Sheehan Syndrome 23 Years After Post-Partum Hemorrhage, Igbayilola Dosunmu, Ali Tariq Alvi, Sarah Kaufman, Ayesha Malik

East Florida Division GME Research Day 2023

Please see supplemental content for full abstract with figures and references.

Sheehan syndrome is defined as ischemic necrosis of pituitary gland following massive postpartum hemorrhage leading to panhypopituitarism. It has an insidious course with multitude of presentations. The majority of cases remain undiagnosed for many years after the delivery with average time following postpartum hemorrhage to diagnosis of Sheehan syndrome is believed to be almost 13 years according to one study. Here, we present a unique case of late onset of Sheehan syndrome 23 years after the last childbirth which was complicated by hemorrhage. To our knowledge, this is the …

When Hypothyroidism Goes Unchecked, Jeong Hwan J. Kim, Yasimin Taheri, Matt Rostami, Ian Joel, Jasprit Takher

Far West Division GME Research Day 2023

No abstract provided.

Staph What?: An Uncommon Species Of Staphylococcus Endocarditis In An Atypical Case Of Diabetic Ketoacidosis, Gilberto Rivera-Gonzalez, Habiba Khan, Harsimrandeep Bhatti, Jazmine Duran, Caleb Nieves, Paul Mathew

Central & West Texas GME Research Day 2023

No abstract provided.

Creating Change In Pediatric Health Disparities: Utilizing Systemsbased Thinking To Overcome Disparities Affecting Pediatric Type 1 Diabetes In Kentucky, Sydney Speed

Lewis Honors College Thesis Collection

Healthcare disparities are perpetuated and upheld for patients with type 1 diabetes (T1D) in rural and underserved urban areas of Kentucky. By adopting systems-based thinking, we can identify areas of the healthcare system to change to eliminate these disparities. Namely, key leverage points of this system include distribution and utilization of resources, finances and the movement of money, and communication pathways. To address the disparities surrounding pediatric T1D in Kentucky, a state-wide medical event called Kentucky Diabetes Family Day (KDFD) was hosted. The focus of this event was to lessen the effects of these specific healthcare disparities by altering key …

Amiodarone-Induced Thyrotoxicosis Type 2 : Utilization Of Color-Flow Doppler Sonography For Diagnosis, Sam Joseph, Larissa Check, Donald Eagerton

South Atlantic Division GME Research Day 2023

No abstract provided.

Myxedema: A Rapidly Cured Psychosis In The Setting Of Bipolar Disorder, Kavanya Feustel, Jeffrey Ramsey, Kelly Schulte, Jacob Keeling, Joel Witter

Continental, MidAmerica, & Mountain Divisions GME Research Day 2023

No abstract provided.

New Onset Hashimoto’S Thyroiditis Associated With Severe Rhabdomyolysis After Infection With Covid19, Nova Mebane, Jacqueline M. Phillips, Cynthia Salloum, Neva Mebane, Daniel Park

Gulf Coast Division GME Research Day 2023

No abstract provided.

Non-Pharmaceutical Symptom Management In Patients With Pcos, Allison Stern

Capstone Showcase

Polycystic Ovarian Syndrome (PCOS) is a relatively common diagnosis among biological females. There are many variations of presentations among patients with PCOS that require an individualized and tailored treatment plan for symptom management. Although there are pharmaceutical medications that can be used for PCOS symptoms, some patients’ symptoms might not be fully managed, or they might prefer to focus on non-pharmaceutical options for their symptoms instead. Therefore, it is important for clinicians to be familiar with alternatives to the mainstay of pharmaceutical treatment.

Vitamin D Enhanced Vitamin D Receptor (Vdr) Inhibition Of Nlrp3 Inflammasome Activation Can Attenuate The Development Of Autoimmune Thyroiditis, Alexzon Mandac

Capstone Showcase

Autoimmune Thyroiditis (AIT) is a prevalent autoimmune disease affecting approximately 2% of the population. Characterized by the gradual loss of thyroid function through an autoimmune attack on the thyroid gland, the disease manifests symptoms that negatively affect one’s quality of life. The mechanisms behind the disease’s pathophysiology are not fully understood; however, researchers are examining the involvement of the NLRP3 inflammasome in the disease. This thesis will address the question of whether Vitamin D can act as an inhibitor of the NLRP3 inflammasome and attenuate the progression of AIT in mouse model. Current investigations explore the effects of NLRP3 inhibition …

Association Of Diabetes Prevalence With Labor Force Participation Rates In Kentucky Counties, Ryan Montgomery

MPA/MPP/MPFM Capstone Projects

Compared to other states in the USA, Kentucky has one of the highest rates of diagnosed diabetes and one of the lowest levels of labor force participation. This project employs a multivariable linear regression model to estimate the correlation between county-level diabetes prevalence and county-level labor force participation rates in Kentucky counties from 2015-2019, using publicly available data from the Centers for Disease Control’s Behavioral Risk Factor Surveillance System (BRFSS) and the U.S. Census Bureau’s American Community Survey (ACS). Labor force participation rates serve as the dependent variable and diabetes prevalence rates serve as the primary independent variable, alongside nine …

The Short- And Long-Term Readmission Of Four Major Categories Of Digestive System Cancers: Does Obesity Or Metabolic Disorder Matter?, Yan Li, Xiaoqin Wu, Yongfeng Song, Peipei Wang, Bofei Zhang, Bingzhou Guo, Ziwei Liu, Yafei Wu, Shanshan Shao, Yiping Cheng, Honglin Guo, Xiude Fan, Jiajun Zhao

Faculty, Staff and Student Publications

Purpose: Patients with digestive system cancers (DSCs) are at a high risk for hospitalizations; however, the risk factors for readmission remain unknown. Here, we established a retrospective cohort study to assess the association between metabolic obesity phenotypes and readmission risks of DSC.

Experimental design: A total of 142,753 and 74,566 patients at index hospitalization were ultimately selected from the Nationwide Readmissions Database (NRD) 2018 to establish the 30-day and 180-day readmission cohorts, respectively. The study population was classified into four groups: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). Multivariate Cox …

Receptor-Interacting Protein 1 And 3 Kinase Activity Are Required For High-Fat Diet Induced Liver Injury In Mice, Xiaoqin Wu, Rakesh K Arya, Emily Huang, Megan R Mcmullen, Laura E Nagy

Faculty, Staff and Student Publications

BACKGROUND: The RIP1-RIP3-MLKL-mediated cell death pathway is associated with progression of non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH). Previous work identified a critical role for MLKL, the key effector regulating necroptosis, but not RIP3, in mediating high fat diet-induced liver injury in mice. RIP1 and RIP3 have active N-terminus kinase domains essential for activation of MLKL and subsequent necroptosis. However, little is known regarding domain-specific roles of RIP1/RIP3 kinase in liver diseases. Here, we hypothesized that RIP1/RIP3 kinase activity are required for the development of high fat diet-induced liver injury.

METHODS:Rip1K45A/K45A and Rip3K51A/K51A kinase-dead mice on a C57BL/6J background and their littermate …

School-Based Intervention Impacts Availability Of Vegetables And Beverages In Participants’ Homes, Erin A Hudson, Marissa Burgermaster, Sophia M Isis, Matthew R Jeans, Sarvenaz Vandyousefi, Matthew J Landry, Rebecca Seguin-Fowler, Joya Chandra, Jaimie Davis

Faculty, Staff and Student Publications

As rates of metabolic syndrome rise, children consume too few vegetables and too much added sugar. Because children tend to eat what is available at home, the home environment plays a key role in shaping dietary habits. This secondary analysis evaluated the effects of a school-based gardening, cooking, and nutrition education intervention (TX Sprouts) compared to control on the availability of vegetables, fruit juice, and sugar-sweetened beverages (SSBs) at home. In the TX Sprouts cluster-randomized trial, 16 schools were randomized to TX Sprouts (

The Health-Promoting Effects And The Mechanism Of Intermittent Fasting, Simin Liu, Min Zeng, Weixi Wan, Ming Huang, Xiang Li, Zixian Xie, Shang Wang, Yu Cai

Faculty, Staff and Student Publications

Intermittent fasting (IF) is an eating pattern in which individuals go extended periods with little or no energy intake after consuming regular food in intervening periods. IF has several health-promoting effects. It can effectively reduce weight, fasting insulin levels, and blood glucose levels. It can also increase the antitumor activity of medicines and cause improvement in the case of neurological diseases, such as memory deficit, to achieve enhanced metabolic function and prolonged longevity. Additionally, IF activates several biological pathways to induce autophagy, encourages cell renewal, prevents cancer cells from multiplying and spreading, and delays senescence. However, IF has specific adverse …

Review Article: New Treatments For Advanced Differentiated Thyroid Cancers And Potential Mechanisms Of Drug Resistance, Sarah Hamidi, Marie-Claude Hofmann, Priyanka C Iyer, Maria E Cabanillas, Mimi I Hu, Naifa L Busaidy, Ramona Dadu

Faculty, Staff and Student Publications

The treatment of advanced, radioiodine refractory, differentiated thyroid cancers (RR-DTCs) has undergone major advancements in the last decade, causing a paradigm shift in the management and prognosis of these patients. Better understanding of the molecular drivers of tumorigenesis and access to next generation sequencing of tumors have led to the development and Food and Drug Administration (FDA)-approval of numerous targeted therapies for RR-DTCs, including antiangiogenic multikinase inhibitors, and more recently, fusion-specific kinase inhibitors such as RET inhibitors and NTRK inhibitors. BRAF + MEK inhibitors have also been approved for BRAF-mutated solid tumors and are routinely used in RR-DTCs in …

Examining The Effects Of Hyperglycemia On Retinal Regeneration, Emmanuella Ec Kyllians

Theses and Dissertations--Biology

Diabetes is a disease that affects how the body processes glucose, leading to a cascade of other complications, one of which is diabetic retinopathy (DR). DR is a neurovascular disease that affects the retina and research has revealed the role of retinal neurodegeneration in its development. Animal models like zebrafish have emerged as important tools for studying the molecular and cellular mechanisms underlying DR. On the other hand, retinitis pigmentosa (RP) is a degenerative disease that involves the progressive degeneration of rods and cones, and hyperglycemia has been found to impair regeneration. Therefore, this study aims to examine the effects …

Protocol For The Promoting Resilience In Stress Management (Prism) Intervention: A Multi-Site Randomized Controlled Trial For Adolescents With Type 1 Diabetes, Maeve B O'Donnell, Samantha R Scott, Britney M Ellisor, Viena T Cao, Chuan Zhou, Miranda C Bradford, Catherine Pihoker, Daniel J Desalvo, Faisal S Malik, Marisa E Hilliard, Abby R Rosenberg, Joyce P Yi-Frazier

Faculty, Staff and Students Publications

BACKGROUND: Adolescents with type 1 diabetes (T1D) are at high risk for elevated diabetes distress, which greatly impacts diabetes management, glycemic outcomes and overall quality of life. Developing protective skills and "resilience resources" to navigate adversity and manage diabetes distress has high potential to help adolescents with T1D achieve optimal behavioral, psychological, and health outcomes. The "Promoting Resilience in Stress Management" (PRISM) program is a manualized, brief, skills-based intervention delivered over 6 months via two 45-60 min one-on-one sessions and a family meeting with a PRISM coach, and supplemented by booster calls and a digital app. This trial (PRISM versus …

Milder Loss Of Insulin-Containing Islets In Individuals With Type 1 Diabetes And Type 2 Diabetes-Associated Tcf7l2 Genetic Variants, Maria J Redondo, Sarah J Richardson, Daniel Perry, Charles G Minard, Alice L J Carr, Todd Brusko, Irina Kusmartseva, Alberto Pugliese, Mark A Atkinson

Faculty, Staff and Students Publications

AIMS/HYPOTHESIS: TCF7L2 variants are the strongest genetic risk factor for type 2 diabetes. In individuals with type 1 diabetes, these variants are associated with a higher C-peptide AUC, a lower glucose AUC during an OGTT, single autoantibody positivity near diagnosis, particularly in individuals older than 12 years of age, and a lower frequency of type 1 diabetes-associated HLA genotypes. Based on initial observations from clinical cohorts, we tested the hypothesis that type 2 diabetes-predisposing TCF7L2 genetic variants are associated with a higher percentage of residual insulin-containing cells (ICI%) in pancreases of donors with type 1 diabetes, by examining genomic data …

Nanocurcumin Combined With Insulin Alleviates Diabetic Kidney Disease Through P38/P53 Signaling Axis, Raghu Ganugula, Nikhil K Nuthalapati, Subhash Dwivedi, Dianxiong Zou, Meenakshi Arora, Richard Friend, David Sheikh-Hamad, Rita Basu, M N V Ravi Kumar

Faculty, Staff and Students Publications

Treatments for diabetic kidney disease (DKD) mainly focus on managing hyperglycemia and hypertension, but emerging evidence suggests that inflammation also plays a role in the pathogenesis of DKD. This 10-week study evaluated the efficacy of daily oral nanoparticulate-curcumin (nCUR) together with long-acting insulin (INS) to treat DKD in a rodent model. Diabetic rats were dosed with unformulated CUR alone, nCUR alone or together with INS, or INS alone. The progression of diabetes was reflected by increases in plasma fructosamine, blood urea nitrogen, creatinine, bilirubin, ALP, and decrease in albumin and globulins. These aberrancies were remedied by nCUR+INS or INS but …

Weight Strategy In Older Adults With Obesity: Calorie Restriction Or Not?, Georgia Colleluori, Dennis T Villareal

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Along with the marked increase in the population of older adults with obesity is the need for effective strategies to treat aging- and obesity-related complications. This review highlights recent progress in obesity management in older adults.

RECENT FINDINGS: Although calorie restriction is needed to significantly reduce fat mass, an exercise protocol is crucial to ameliorate functional outcomes. The addition of a resistance exercise protocol improves the response of muscle protein synthesis to anabolic stimuli, preventing the calorie restriction-induced reduction in muscle and bone mass. The addition of an aerobic exercise protocol improves cardiorespiratory fitness and cognitive function. …