Endocrine System Diseases Commons^™

Multimorbidity In Diverse Populations: Stratified Analysis Of Race/Ethnicity, Age, Obesity, And Healthcare Costs, Manal Alshakhs

Theses and Dissertations (ETD)

This research aims to fill an essential gap in understanding how Body Mass Index (BMI) cutoffs relate to multimorbidity across races in the United States (US). Given the significant and growing rates of obesity and multimorbidity, as well as the known differences in healthy fat distribution among different races, this is an important area of research. BMI is a widely used but imperfect measure of obesity, as it does not account for differences in body composition. However, it is still used as a diagnostic tool. It is vital to ensure that the cutoffs used to define obesity are appropriate for …

Long-Term Maternal Metabolic And Cardiovascular Phenotypes After A Pregnancy Complicated By Mild Gestational Diabetes Mellitus Or Obesity, Ashley N Battarbee, Lisa Mele, Mark B Landon, Michael W Varner, Brian M Casey, Uma M Reddy, Ronald J Wapner, Dwight J Rouse, John M Thorp, Edward K Chien, George Saade, Beth A Plunkett, Sean C Blackwell

Faculty, Staff and Student Publications

Objective:

To evaluate the association of mild gestational diabetes (GDM) and obesity with metabolic and cardiovascular markers 5-10 years after pregnancy.

Study Design:

This was a secondary analysis of 5-10 year follow-up study of a mild GDM treatment trial and concurrent observational cohort of participants ineligible for the trial with abnormal 1-hour glucose challenge test only. Participants with 2-hour glucose tolerance test at follow-up were included. The primary exposures were mild GDM and obesity. The outcomes were insulinogenic index (IGI), 1/HOMA-IR, and cardiovascular markers VEGF, VCAM-1, CD40L, GDF-15, and ST-2. Multivariable linear regression estimated the association of GDM and obesity …

Fit24, A Digital Health Intervention To Reduce Type 2 Diabetes Risk Among Hispanic Youth: Protocol For A Feasibility Pilot Study, Erica G Soltero, Callie Lopez, Salma M Musaad, Teresia M O'Connor, Debbe Thompson

Faculty, Staff and Students Publications

BACKGROUND: Poor physical activity (PA) and sleep behaviors in Hispanic adolescents contributes to increased risk for type 2 diabetes. Commonly owned digital devices and services like smartphones and text-messaging are highly used among adolescents and are promising intervention tools for reaching this age group. Personal activity trackers assess activity and sleep, making them ideal tools for addressing these behaviors. We propose to examine the feasibility of a 12-week intervention that uses theoretically grounded text messages and a Fitbit device to improve PA and sleep among Hispanic adolescents with obesity, as compared to a wait-list control group with a Fitbit device …

The Circadian E3 Ligase Fbxl21 Regulates Myoblast Differentiation And Sarcomere Architecture Via Myoz1 Ubiquitination And Nfat Signaling, Bo Hu, Jian-Xing Ma, Adam S Duerfeldt

Faculty, Staff and Student Publications

Diabetic retinopathy and age-related macular degeneration are common retinal diseases with shared pathophysiology, including oxidative stress-induced inflammation. Cellular mechanisms responsible for converting oxidative stress into retinal damage are ill-defined but have begun to clarify. One common outcome of retinal oxidative stress is mitochondrial damage and subsequent release of mitochondrial DNA into the cytosol. This leads to activation of the cGAS-STING pathway, resulting in interferon release and disease-amplifying inflammation. This review summarizes the evolving link between aberrant cGAS-STING signaling and inflammation in common retinal diseases and provides prospective for targeting this system in diabetic retinopathy and age-related macular degeneration. Further defining …

Clinical Outcomes Of Immune Checkpoint Inhibitor Diabetes Mellitus At A Comprehensive Cancer Center, Rebecca Jeun, Priyanka C Iyer, Conor Best, Victor Lavis, Jeena M Varghese, Sireesha Yedururi, Veronica Brady, Isabella C Glitza Oliva, Ramona Dadu, Denai R Milton, Kristy Brock, Sonali Thosani

Faculty, Staff and Student Publications

Introduction: Immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) is a rare adverse event. In this study, we characterize clinical outcomes of patients with ICI-DM and evaluate survival impact of this complication on melanoma patients.

Research design & methods: We conducted a retrospective review of 76 patients diagnosed with ICI-DM from April 2014 to December 2020.

Results: 68% of patients presented in diabetic ketoacidosis, 16% had readmissions for hyperglycemia, and hypoglycemia occurred in 70% of patients after diagnosis. Development of ICI-DM did not impact overall survival or progression-free survival in melanoma patients.

Conclusion: Development of ICI-DM is associated with long-term insulin dependence …

Uh-02 A Case Report Of The Potential Link Between Pulmonary Fibrosis And Diabetes Mellitus, Bryson T. Rose, Isabella Nielson, Nnenna Igwe

SC Upstate Research Symposium

Pulmonary fibrosis is a chronic lung disease that is characterized by the progressive and irreversible scarring of the lung tissue. This scarring greatly diminishes the efficiency of pulmonary function. After being diagnosed with pulmonary fibrosis, patients live, on average, only three to five years. Diabetes mellitus is known to damage the tissue and blood vessels in organs such as the heart and kidneys due to increased intravascular pressure.

According to recent research, diabetes mellitus has also been linked to similar damage in the lungs. Additionally, a 2021 meta-analysis and systematic review of idiopathic pulmonary fibrosis suggests an association between diabetes …

Diagnostic Performance Of Afirma And Interpace Diagnostics Genetic Testing In Indeterminate Thyroid Nodules: A Single Center Study †, Emad Kandil, Tyler A. Metz, Peter P. Issa, Mohamed Aboueisha, Mahmoud Omar, Abdallah S. Attia, Bert Chabot, Mohammad Hussein, Krzysztof Moroz, Mohamed Shama, Eman Toraih

School of Medicine Faculty Publications

Indeterminate thyroid nodules (ITN) represent 20–30% of biopsied nodules, with a 10–60% risk of malignancy. Molecular testing can stratify the risk of malignancy among ITNs, and subsequently reduce the need for unnecessary diagnostic surgery. We aimed to assess the performance of these molecular tests at a single institution. Patients with Bethesda III, IV, and V nodules with Afirma and Interpace Diagnostics genetic testing data from November 2013 to November 2021 were included. Three cohorts were formed, including GSC + XA, ThyGeNEXT + ThyraMIR, and GSC + GEC. Statistical analysis determined the sensitivity, specificity, positive predictive value (PPV), negative predictive value …

Relationships Among Biochemical Measures In Children With Diabetic Ketoacidosis, Nicole S Glaser, Michael J Stoner, Maria Y Kwok, Kimberly S Quayle, Kathleen M Brown, Jeff E Schunk, Jennifer L Trainor, Julie K Mcmanemy, Leah Tzimenatos, Arleta Rewers, Lise E Nigrovic, Jonathan E Bennett, Sage R Myers, Mckenna Smith, T Charles Casper, Nathan Kuppermann

Faculty, Staff and Students Publications

OBJECTIVES: Investigating empirical relationships among laboratory measures in children with diabetic ketoacidosis (DKA) can provide insights into physiological alterations occurring during DKA. We determined whether alterations in laboratory measures during DKA conform to theoretical predictions.

METHODS: We used Pearson correlation statistics and linear regression to investigate correlations between blood glucose, electrolytes, pH and PCO2 at emergency department presentation in 1,681 pediatric DKA episodes. Among children with repeat DKA episodes, we also assessed correlations between laboratory measures at the first vs. second episode.

RESULTS: pH and bicarbonate levels were strongly correlated (r=0.64), however, pH and PCO2 were only loosely correlated (r=0.17). …

Biomarker Metabolite Discovery For Pancreatic Cancer Using Machine Learning, Immanuelle Kezia, Linda Erlina, Aryo Tedjo, Fadilah Fadilah

Indonesian Journal of Medical Chemistry and Bioinformatics

Pancreatic cancer is one of the deadliest cancers in the world. This cancer is caused by multiple factors and mostly detected at late stadium. Biomarker is a marker that can identify some diseases very specific. For pancreatic cancer, biomarker has been recognized using blood sample known as liquid biopsy, breath, pancreatic secret, and tumor marker CA19-9. Those biomarkers are invasive, so we want to identify the disease using a very convenient method. Metabolite is product from cell metabolism. Metabolites can become a biomarker especially from difficult diseases. In this paper, we want to find biomarker from metabolite using machine learning …

Conjunctival And Lingual Mucosal Neuromas Without Multiple Endocrine Neoplasia Type 2b, Talia N. Shoshany, Christopher J. Rapuano, Tatyana Milman

Wills Eye Hospital Papers

Purpose: To report a patient with conjunctival and buccal neuromas and enlarged corneal nerves without Multiple Endocrine Neoplasia 2B (MEN2B).

Observations: A 28-year-old female presented with progressively enlarging bilateral limbal conjunctival growths. Slit lamp examination was notable for enlarged corneal nerves and well-circumscribed gelatinous subepithelial limbal nodules. Systemic examination revealed similar lesions on the tongue. Conjunctival biopsy demonstrated a mucosal neuroma. The patient underwent endocrine workup for MEN2B and genetic testing for the RET-proto oncogene mutations, all of which were negative.

Conclusions and Importance: The findings in our patient may be compatible with pure mucosal neuroma syndrome. The pattern of …

Taking A Load Off: User Perceptions Of Smart Offloading Walkers For Diabetic Foot Ulcers Using The Technology Acceptance Model, M G Finco, Gozde Cay, Myeounggon Lee, Jason Garcia, Elia Salazar, Tze-Woei Tan, David G Armstrong, Bijan Najafi

Center on Aging Staff Publications

People with diabetic foot ulcers (DFUs) are commonly prescribed offloading walkers, but inadequate adherence to prescribed use can be a barrier to ulcer healing. This study examined user perspectives of offloading walkers to provide insight on ways to help promote adherence. Participants were randomized to wear: (1) irremovable, (2) removable, or (3) smart removable walkers (smart boot) that provided feedback on adherence and daily walking. Participants completed a 15-item questionnaire based on the Technology Acceptance Model (TAM). Spearman correlations assessed associations between TAM ratings with participant characteristics. Chi-squared tests compared TAM ratings between ethnicities, as well as 12-month retrospective fall …

Affinity Purification Of Serum-Derived Anti-Ia-2 Autoantibodies In Type 1 Diabetes Using A Novel Mbp-Ia-2 Fusion Protein, Thilini Mendis, Barbora Filipova, Jing Jing Wang, Massimo Pietropaolo, Michael W Jackson

Faculty, Staff and Students Publications

Autoantibodies targeting epitopes contained within the intracellular domain (IC) of the protein phosphatase-like islet antigen 2 (IA-2) are a common marker of autoimmune type 1 diabetes (T1D), however the isolation of genuine, serum derived anti-IA-2 autoantibodies has proven challenging due to a lack of suitable bioassays. In the current study, an ELISA format was developed for affinity purification of human anti-IA-2ic autoantibodies utilizing a fusion protein (FP) incorporating maltose binding protein and the full-length IA-2IC domain. Using a T1D patient cohort validated for anti-IA-2ic autoantibodies by commercial ELISA, we demonstrate the MBP-IA-2ic FP ELISA detects serum anti-IA-2IC autoantibodies from 3 …

Epigenome-Wide Association Study Reveals Cpg Sites Associated With Thyroid Function And Regulatory Effects On Klf9, Antoine Weihs, Layal Chaker, Tiphaine C Martin, Kim V E Braun, Purdey J Campbell, Simon R Cox, Myriam Fornage, Christian Gieger, Hans J Grabe, Harald Grallert, Sarah E Harris, Brigitte Kühnel, Riccardo E Marioni, Nicholas G Martin, Daniel L Mccartney, Allan F Mcrae, Christa Meisinger, Joyce B J Van Meurs, Jana Nano, Matthias Nauck, Annette Peters, Holger Prokisch, Michael Roden, Elizabeth Selvin, Marian Beekman, Diana Van Heemst, Eline P Slagboom, Brenton R Swenson, Adrienne Tin, Pei-Chien Tsai, Andre Uitterlinden, W Edward Visser, Henry Völzke, Melanie Waldenberger, John P Walsh, Anna Köttgen, Scott G Wilson, Robin P Peeters, Jordana T Bell, Marco Medici, Alexander Teumer

Faculty, Staff and Student Publications

Background:

Thyroid hormones play a key role in differentiation and metabolism and are known regulators of gene expression through both genomic and epigenetic processes including DNA methylation. The aim of this study was to examine associations between thyroid hormones and DNA methylation.

Methods:

We carried out a fixed-effect meta-analysis of epigenome-wide association study (EWAS) of blood DNA methylation sites from 8 cohorts from the ThyroidOmics Consortium, incorporating up to 7073 participants of both European and African ancestry, implementing a discovery and replication stage. Statistical analyses were conducted using normalized beta CpG values as dependent and log-transformed thyrotropin (TSH), free thyroxine, …

Chronic Kidney Disease Promotes Cerebral Microhemorrhage Formation, Chuo Fang, Wei Ling Lau, Jiahong Sun, Rudy Chang, Adrian Vallejo, Donghy Lee, Jihua Liu, Han Liu, Yu-Han Hung, Yitong Zhao, Annlia Paganini-Hill, Rachita K. Sumbria, David H. Cribbs, Mark J. Fisher

Pharmacy Faculty Articles and Research

Background

Chronic kidney disease (CKD) is increasingly recognized as a stroke risk factor, but its exact relationship with cerebrovascular disease is not well-understood. We investigated the development of cerebral small vessel disease using in vivo and in vitro models of CKD.

Methods

CKD was produced in aged C57BL/6J mice using an adenine-induced tubulointerstitial nephritis model. We analyzed brain histology using Prussian blue staining to examine formation of cerebral microhemorrhage (CMH), the hemorrhagic component of small vessel disease and the neuropathological substrate of MRI-demonstrable cerebral microbleeds. In cell culture studies, we examined effects of serum from healthy or CKD patients and …

Identification Of Small-Molecule Inhibitors Of The Salmonella Frab Deglycase Using A Live-Cell Assay, Anice Sabag-Daigle, Erin F Boulanger, Pankajavalli Thirugnanasambantham, Jamison D Law, Alex J Bogard, Edward J Behrman, Venkat Gopalan, Brian M M Ahmer

Faculty, Staff and Student Publications

Nontyphoidal salmonellosis is one of the most significant foodborne diseases in the United States and globally. There are no vaccines available for human use to prevent this disease, and only broad-spectrum antibiotics are available to treat complicated cases of the disease. However, antibiotic resistance is on the rise and new therapeutics are needed. We previously identified the Salmonella fraB gene, that mutation of causes attenuation of fitness in the murine gastrointestinal tract. The FraB gene product is encoded in an operon responsible for the uptake and utilization of fructose-asparagine (F-Asn), an Amadori product found in several human foods. Mutations in …

Hypoglycemia: A Mimic Of Global Ischemic Injury, Zachary Leavitt, Jay Babu, Sannah Vasaya, Robert Balsinger, Aroucha Vickers

Annual Research Symposium

No abstract provided.

Hepatocytes Demarcated By Ephb2 Contribute To The Progression Of Nonalcoholic Steatohepatitis, Yang Xiao, Kirill Batmanov, Wenxiang Hu, Kun Zhu, Alexander Y Tom, Dongyin Guan, Chunjie Jiang, Lan Cheng, Sam J Mccright, Eric C Yang, Matthew R Lanza, Yifan Liu, David A Hill, Mitchell A Lazar

Faculty, Staff and Students Publications

Current therapeutic strategies for treating nonalcoholic steatohepatitis (NASH) have failed to alleviate liver fibrosis, which is a devastating feature leading to hepatic dysfunction. Here, we integrated single-nucleus transcriptomics and epigenomics to characterize all major liver cell types during NASH development in mice and humans. The bifurcation of hepatocyte trajectory with NASH progression was conserved between mice and humans. At the nonalcoholic fatty liver (NAFL) stage, hepatocytes exhibited metabolic adaptation, whereas at the NASH stage, a subset of hepatocytes was enriched for the signatures of cell adhesion and migration, which were mainly demarcated by receptor tyrosine kinase ephrin type B receptor …

Genome-Wide Screening Reveals The Genetic Basis Of Mammalian Embryonic Eye Development, Justine M Chee, Louise Lanoue, Dave Clary, Kendall Higgins, Lynette Bower, Ann Flenniken, Ruolin Guo, David J Adams, Fatima Bosch, Robert E Braun, Steve D M Brown, H-J Genie Chin, Mary E Dickinson, Chih-Wei Hsu, Michael Dobbie, Xiang Gao, Sanjeev Galande, Anne Grobler, Jason D Heaney, Yann Herault, Martin Hrabe De Angelis, Fabio Mammano, Lauryl M J Nutter, Helen Parkinson, Chuan Qin, Toshi Shiroishi, Radislav Sedlacek, J-K Seong, Ying Xu, Brian Brooks, Colin Mckerlie, K C Kent Lloyd, Henrik Westerberg, Ala Moshiri

Faculty, Staff and Students Publications

BACKGROUND: Microphthalmia, anophthalmia, and coloboma (MAC) spectrum disease encompasses a group of eye malformations which play a role in childhood visual impairment. Although the predominant cause of eye malformations is known to be heritable in nature, with 80% of cases displaying loss-of-function mutations in the ocular developmental genes OTX2 or SOX2, the genetic abnormalities underlying the remaining cases of MAC are incompletely understood. This study intended to identify the novel genes and pathways required for early eye development. Additionally, pathways involved in eye formation during embryogenesis are also incompletely understood. This study aims to identify the novel genes and pathways …

Energy Intake At The Intersection Of The Clock And Ageing, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

Calorie restriction and timed dietary intake are two approaches known to increase lifespan or delay age-associated diseases. New studies reveal the importance of the ‘how much’ and ‘when’ of dietary intake in ageing modulation and collectively demonstrate how protection of the internal clock by diet can delay the ageing process.

Psychosocial, Medical, And Demographic Variables Associated With Parent Mealtime Behavior In Young Children Recently Diagnosed With Type 1 Diabetes, Caroline Gonynor, Christine Wang, Carrie Tully, Maureen Monaghan, Randi Streisand, Marisa E Hilliard

Faculty, Staff and Students Publications

OBJECTIVE: Managing young children's mealtime concerns can be challenging after type 1 diabetes (T1D) diagnosis because of developmental factors and diabetes management demands. To identify potential intervention targets, we evaluated medical, psychosocial, and demographic factors in relation to parents' engagement in problem mealtime behaviors (e.g., pressure to eat, restriction).

METHOD: Parents (N = 157) of young children (age 1-6 years) reported on psychosocial variables (parent fear of hypoglycemia, family functioning, parent problem solving, and parents' problem mealtime behavior frequency and perceptions of being problematic) within 2 months after T1D diagnosis. Hierarchical regression analyses examined associations among psychosocial variables, demographics (child …

Emotional Distress, Self-Management, And Glycemic Control Among Participants Enrolled In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness (Grade) Study, Jeffrey S Gonzalez, Heidi Krause-Steinrauf, Ionut Bebu, Gladys Crespo-Ramos, Claire J Hoogendoorn, Aanand D Naik, Andrea Waltje, Elizabeth Walker, Dominic Ehrmann, Janet Brown-Friday, Andrea Cherrington

Faculty, Staff and Student Publications

OBJECTIVE: We examined emotional distress in relation to metformin adherence, overall diabetes self-management, and glycemic control among adults with early type 2 diabetes (T2DM) enrolled in the GRADE study.

METHODS: Linear regression models examined cross-sectional associations of baseline depression symptoms and diabetes distress with adherence to metformin, self-management, and HbA1c, adjusting for covariates. Cognitive-affective (e.g., sadness) and somatic (e.g., sleep/appetite disturbance) depression symptoms and diabetes distress subscales were also examined.

RESULTS: This substudy of 1,739 GRADE participants (56 % Non-Hispanic White, 18 % Non-Hispanic Black, 17 % Hispanic, 68 % male, mean[SD] age = 57.96[10.22] years, diabetes duration = 4.21[2.81] …

Glucocorticoid Therapy As First-Line Treatment In Primary Hypophysitis: A Systematic Review And Individual Patient Data Meta-Analysis, Brijesh Krishnappa, Ravikumar Shah, Saba Samad Memon, Chakra Diwaker, Anurag R Lila, Virendra A Patil, Nalini S Shah, Tushar R Bandgar

Faculty, Staff and Student Publications

OBJECTIVES: High-dose glucocorticoids are associated with improved recovery of deficits in primary autoimmune hypophysitis (PAH), but optimal dosing, route, and duration are unclear.

DESIGN: We reviewed literature for first-line glucocorticoid treatment in PAH until December 2021 and performed an individual patient data meta-analysis to analyze clinical, hormonal, and radiological outcomes with respect to route, dose, and duration (12 weeks) of glucocorticoid treatment according to disease severity.

RESULTS: A total of 153 PAH patients from 83 publications were included. The median age at presentation was 41 (32.5-48) years with a female preponderance (70.3%). Visual field recovery was significantly better with i.v. …

Circadian Clock And Temporal Meal Pattern, Xin Li, Zheng Sun

Faculty, Staff and Students Publications

The central circadian clock in the brain controls the time-of-the-day variations in acute meal responses, with a low glycemic response but a high satiety/thermogenic response to meals consumed at waking compared to other time points. Consistently, studies show that consuming a significant proportion of calories, particularly carbohydrates, in breakfast is beneficial for the chronic management of obesity and its associated metabolic syndrome, compared to consuming identical meals at dinner. Conversely, breakfast skipping or/and late dinner can have unfavorable metabolic outcomes. It remains controversial how meal frequency affects metabolic health. In contrast, irregular meals, especially irregular breakfasts, show consistent adverse metabolic …

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 …

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 …