Endocrinology, Diabetes, and Metabolism Commons^™

Dual Targeting Of Orphan Nuclear Receptors Nr4a1 And Nr4a2 For Nonhormonal Endometriosis Therapy, Wai Ning Tiffany Tsui, Yuri Park, Srijana Upadhyay, Da Mi Kim, Lei Zhang, Gus Wright, Amanuel Hailemariam, Arafat Rahman Oany, Sang Jun Han, Stephen Safe

Faculty, Staff and Students Publications

Previous studies show that orphan nuclear receptor 4A1 (NR4A1) regulates endometriotic cell growth, survival, estrogen receptor β (ERβ), mechanistic target of rapamycin signaling and fibrosis. NR4A2 is also expressed in epithelial and stromal derived endometriotic cells, and in this study the effects of 1,1-bis(3'-indolyl)-(3,5-disubstitutedphenyl)methane (DIM-3,5) dual NR4A1/nuclear receptor 4A2 (NR4A2) ligands and knockdown of NR4A1 and NR4A2 were investigated. The dual NR4A1/2 DIM-3,5 analogs inhibited previously identified proendometriotic pathways and gene products, and they also inhibited TWIST1 and multiple markers associated with epithelial-to-mesenchymal transition (EMT). The results show that both NR4A1 and NR4A2 regulate the same pathways, including endometriotic cell …

Diabetes-Related Foot Complications And Socioeconomic Influences Among Hispanic Males In South Texas: A Scoping Review, Mariana J. Rodriguez, Demian Rodriguez, Amanda L. Killeen

School of Podiatric Medicine - Student Research

Introduction: Diabetes mellitus is the 7^th leading cause of death in the United States and is 6^th in the state of Texas. Counties from South Texas are primarily affected with higher rates of diabetes than both the state and national average. Diabetes mellitus is a complex and progressive disease which can affect multiple systems of the body, leading to serious complications if untreated, especially in the lower extremities. Uncontrolled diabetes is often associated with diabetic foot ulcers (DFU), foot infections, and lower extremity amputations (LEA). South Texas is a region predominantly populated by Hispanic Americans who are disproportionally …

Associations Among Human Milk Polyunsaturated Fatty Acids And Infant Sleep Patterns: A Cross-Sectional Study, Ana M Palacios, Dominick J Lemas, Bridget E Young, Erik Parker, Stephanie Dickinson, Nandi Marshall, Kelly L Sullivan, Haley Wilt, Michelle I Cardel, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: Infant sleep is critical for cognitive, emotional, and long-term health outcomes. Although diet-sleep relationships are established, limited research has explored how polyunsaturated fatty acids (PUFAs) in human milk (HM) relate to infant sleep.

Objectives: This study aims to examine associations between PUFAs in HM and sleep patterns in 2-mo-old infants exclusively fed with HM.

Methods: This cross-sectional secondary analysis used data from a lactation cookie trial involving 131 parents of healthy, term infants. Participants provided a fasting HM sample and completed sociodemographic and Brief Infant Sleep Questionnaire surveys. Multivariate linear models were adjusted for infant sex assigned at birth, …

Repeated Withdrawal Of A Glpr Agonist Induces Hyperleptinemia And Deteriorates Metabolic Health In Obese Aging Um-Het3 Mice, Nisi Jiang, Jiyuan Yin, Noah Lawrence, Jieyi Meng, Laurence T Maeyens, Ziying Xu, Xin Li, Mbolle Ekane, Ariana Chaudhary, Pengju Cao, Guannan Li, Carolina Solis-Herrera, Yi Zhu, Shangang Zhao

Children’s Nutrition Research Center Staff Publications

GLP-1-based therapy is highly effective in combating aging-associated metabolic diseases. However, the metabolic effects of frequent withdrawal from this therapy in aged, obese mice have not been previously studied. In this study, aged obese UM-HET3 mice were assigned to three groups: Group 1 received no liraglutide treatment (Lira OFF); Group 2 underwent 3 cycles of treatment followed by withdrawal (Lira ON/OFF); and Group 3 remained on continuous treatment (Lira ON). As expected, mice in Group 3 showed reduced body weight and food intake, along with improved metabolic health. In contrast, mice in Group 2 developed hyperleptinemia and visceral fat expansion, …

All-Cause And Cause-Specific Mortality Among Patients With Narcolepsy., Chih-Wei Hsu, Yen-Shan Yang, Yang-Chieh Brian Chen, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Edward Chia-Cheng Lai

Children’s Nutrition Research Center Staff Publications

Importance: Narcolepsy is a sleep disorder potentially affecting mortality, yet evidence on this association remains sparse.

Objective: To examine whether narcolepsy is associated with an increased risk of all-cause and cause-specific mortality.

Design, setting, and participants: This retrospective cohort study used data from the Taiwan National Health Insurance Research Database (NHIRD) from 2001 to 2021, with patients followed up until death or December 31, 2022. Patients were aged 6 years or older with 2 or more narcolepsy diagnoses from psychiatrists or neurologists. Controls were selected from the NHIRD as a population-based sample. Controls without narcolepsy were matched in a 1:4 …

Menopause Factors And Alterations In Gut Microbiota And Insulin Homeostasis: A Cross-Sectional Analysis Of The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Vincent J Maffei, Alain G Bertoni, Alexis C Wood, Jerome I Rotter, Osa Crago, Yii-Der I Chen, Joseph F Petrosino, Kristi L Hoffman, Mark O Goodarzi, Elizabeth T Jensen

Children’s Nutrition Research Center Staff Publications

Aim: To assess the risk for impaired insulin homeostasis as a function of menopause-related factors and gut microbiota dysbiosis in non-diabetic, post-menopausal women.

Materials and methods: Baseline data (n = 175 women) from the Microbiome and Insulin Longitudinal Evaluation Study (MILES) were used, including insulin and dysglycaemia indices calculated from a 2-h oral glucose tolerance test, untargeted peripheral metabolomics, targeted peripheral short chain fatty-acid levels and faecal bacterial microbiota surveyed by whole-metagenomic sequencing.

Results: After adjustment for covariates, menopause age < 50 years and use of hormone replacement therapy (HRT) were associated with lower Matsuda et al. insulin sensitivity index levels (β = -0.232, confidence interval (CI) = [-0.450, -0.014] and β = -0.275, CI = [-0.444, -0.107], respectively) but not pre-menopausal gynaecologic surgery. Pre-menopausal gynaecologic surgery was significantly associated with faecal microbiota beta diversity driven by a relative increase in diabetogenic Ruminococcus gnavus and Clostridium species and a decrease in protective Alistipes species and Akkermansia muciniphila relative abundances. A reduction in two glycerophospholipids in the plasmalogen class significantly statistically mediated an inverse association between gynaecologic surgery before menopause and insulin sensitivity.

Conclusions: Menopause age and history of HRT are more strongly associated with insulin resistance than gynaecologic surgery before menopause. However, …

Weight Loss Remains A Challenge For Idiopathic Intracranial Hypertension Patients: A Retrospective Case Series From Kenya, Zian Muikamba, Jaskirat Sokhi, Jasmit Shah, Sheila Marco, Juzar Hooker, Dilraj Sokhi

Internal Medicine, East Africa

Background Idiopathic intracranial hypertension (IIH) is a neurological condition characterized by elevated intracranial CSF pressure without demonstratable evident causes. The mechanisms leading to a particular predilection for women of childbearing age who are overweight and obese or who have recent rapid weight changes remain imprecisely described. If undiagnosed, it can progress to disabling irreversible visual loss. Weight loss is useful in addition to medical therapy in treating the condition. There is a rise of obesity in sub-Saharan Africa (SSA) but there is little published on IIH.

Methods We conducted a retrospective cross-sectional study at our tertiary regional referral neurology centre …

Calcium Supplementation And The Risk Of Dementia In The Perth Longitudinal Study Of Aging Women: A Post-Hoc Analysis Of A Randomised Clinical Trial For Fracture Prevention, Negar Ghasemifard, Joshua R. Lewis, Simone Radavelli-Bagatini, Simon M. Laws, Blossom C.M. Stephan, Jonathan M. Hodgson, Kun Zhu, Richard L. Prince, Marc Sim

Research outputs 2022 to 2026

Background: Concerns have been raised around whether calcium supplements increase dementia risk. This post-hoc analysis of a five-year double-blind, placebo-controlled randomised trial of calcium supplements for primary fracture prevention evaluated the long-term risk for dementia in older women, randomised to either calcium supplements or placebo. Methods: 1460 community-dwelling dementia-free Australian women (≥70 years) were randomised to 1200 mg/day calcium carbonate (n = 730) or placebo (n = 730) for five years and were observed for an additional 9.5 years afterwards. Over 14.5 years, all-cause dementia events (comprising dementia-related hospitalisations and/or deaths) were identified from linked health records. The influence of …

Classifying A Distinct Form Of Diabetes In Lean Individuals With A History Of Undernutrition: An International Consensus Statement, Pradnyashree Wadivkar, Felix Jebasingh, Nihal Thomas, Chittaranjan S Yajnik, Allan Arthur Vaag, Davis Kibirige, Silver Bahendeka, Mandeep Bajaj, Michael S Boyne, Charlotte Bavuma, Jacko Abodo, Sarah Wild, Ullas Kolthur-Seetharam, Satinath Mukhopadhyay, Noel P Somasundaram, Peter Schwarz, Dirk L Christensen, Faruque Pathan, Angus G Jones, Sandeep Mathur, Sylvia Kehlenbrink, Meredith Hawkins, Vellore Declaration Signatories

Faculty, Staff and Students Publications

Since 1955, a form of diabetes in lean, young (BMI < 18·5 kg/m2, age < 30 years) individuals with a history suggestive of undernutrition from before birth and throughout childhood has been described in the literature. In 1985, WHO formally classified it as malnutrition-related diabetes, but subsequently removed the classification in 1999 over a disagreement as to whether undernutrition was a sufficient risk factor to cause this type of diabetes. Emerging evidence now strongly supports the distinct classification of this unique diabetes phenotype, which is characterised by substantial impairment of pancreatic insulin secretion, with normal hepatic and peripheral insulin sensitivity, an absence of ketoacidosis, and no islet cell autoantibodies. In this consensus statement, we synthesise this evidence to produce a set of common features of the disease, proposed pathogenetic mechanisms, and suggested management and prevention strategies. During a consensus meeting in Vellore, India, in January, 2025, type 5 diabetes was proposed as the nomenclature for this distinct form of diabetes, subsequently formalised at the International Diabetes Federation (IDF) World Diabetes Congress in April, 2025. We call upon the international diabetes community to recognise this distinct form of the disease, and to support the IDF's Type 5 Diabetes Working Group and its goals to promote more research into its phenotype, pathophysiology, and treatment, which will benefit millions of patients worldwide, particularly in low-income and middle-income countries.

Liver-Specific Expression Of Hiv-1 Viral Protein R Causes Hepatic Steatosis And Glucose Intolerance In Male Mice, Neeti Agarwal, Pradip Saha, Claudia E Ramirez Bustamante, Sean M Hartig, Mark A Herman, Ashok Balasubramanyam, Jordan E Lake

Faculty, Staff and Students Publications

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized in people with HIV (PWH), with both HIV and antiretroviral therapy contributing to liver damage and glucose intolerance. However, the role of viral proteins derived from reservoirs in this process remains unclear.

Methods: Adeno-associated virus (AAV) constructs encoding a control protein or HIV-1 viral protein R (Vpr) driven by the thyroxine-binding globulin promoter were administered to male mice (n = 5 per group) fed regular chow or a high-fat diet (HFD). Young adult mice underwent intraperitoneal glucose tolerance testing and magnetic resonance imaging, followed by euthanasia. Liver and adipose tissues …

Characteristics Contributing To The Risk Of Diabulimia In Adults Living In The United States, Danielle Van Hout, Nicole Stendell-Hollis, Tafere Gebreegziabher Belay, Kelly Pritchett

Journal of the Symposium of University Research and Creative Expression

Project Mentor(s): Nicole Stendell-Hollis, PhD, RDN; Tafere G Belay, PhD; Kelly Pritchett, PhD, RDN, CSSD

The purpose of this study was to determine the prevalence and factors that contribute to the risk of diabulimia by using the validated Diabetes Eating Problem Survey-Revised (DEPS-R)¹ screening tool in adults living in the U.S., as well as to examine differences in individuals at-risk and not-at-risk for diabulimia. This observational study included a 30-question Qualtrics survey containing the DEPS-R distributed via various social media outlets and flyers on the CWU Ellensburg campus. Participants were required to be 18 years or older, diagnosed with …

Prevalence Of Diabetes Related To Acculturation, Dietary Quality, And Sedentary Lifestyle In Mexican Americans: National Health And Nutrition Examination Survey 2011 To 2018, Kivima Acevedo

Journal of the Symposium of University Research and Creative Expression

Project Mentor(s): David Gee, PhD; Kathaleen Briggs Early, PhD, RDN, CDCES; Katy Williams, MS, RDN

Objective: This study examined the prevalence of diabetes in Mexican American adults (MA-adults) and how risk factors like acculturation, dietary quality, and sedentary lifestyle contribute to the rising rates of diabetes, using the National Health and Nutrition Survey (NHANES) 2011 to 2018 data. Methods: We analyzed the NHANES data of MA-adults and Non-Hispanic White adults (NHW-adults) (n= 10670) for the association of diabetes and its risk factors (dietary habits and sedentary lifestyle) by acculturation levels. Diet quality was assessed using the Healthy Eating Index (HEI). …

Hubungan Visceral Adiposity Index Dengan Neuropati Diabetik Perifer Pada Pasien Diabetes Melitus Tipe 2, Muhammad Arif Sanusi, Dian Anindita Lubis, Santi Syafril

Jurnal Penyakit Dalam Indonesia

Introduction. Type 2 diabetes mellitus (T2DM) is the leading metabolic disease in Indonesia. Diabetic peripheral neuropathy (DPN), a major complication of T2DM, was associated with insulin resistance and adipose dysfunction. Visceral adiposity index (VAI) is a tool to measure visceral fat as the indicator of adipose dysfunction and insulin sensitivity. The association between VAI and DPN has not been widely researched, especially in Indonesia. This study aims to assess the association between them.

Methods. This was a cross-sectional study conducted on adult patients (aged ≥18 years) with T2DM at H. Adam Malik General Hospital, Medan, from December 2024 …

Toward A Clinically Actionable, Electronic Health Record-Based Machine Learning Model To Forecast 90-Day Change In Hemoglobin A1c In Youth With Type 1 Diabetes: Feasibility And Model Development Study, Erin M. Tallon, David D. Williams, Cintya Schweisberger, Colin Mullaney, Brent Lockee, Diana Ferro, Craig Vandervelden, Mitchell S. Barnes, Angelica Cristello Sarteau, Anna R. Kahkoska, Susana R. Patton, Sanjeev Mehta, Ryan Mcdonough, Marcus Lind, Leonard D'Avolio, Mark A. Clements

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Clinicians currently lack an effective means for identifying youth with type 1 diabetes (T1D) who are at risk for experiencing glycemic deterioration between diabetes clinic visits. As a result, their ability to identify youth who may optimally benefit from targeted interventions designed to address rising glycemic levels is limited. Although electronic health records (EHR)-based risk predictions have been used to forecast health outcomes in T1D, no study has investigated the potential for using EHR data to identify youth with T1D who will experience a clinically significant rise in glycated hemoglobin (HbA1c) ≥0.3% (approximately 3 mmol/mol) between diabetes clinic visits. …

Geriatric Brittle Type 1 Diabetes Mellitus: Case Study And Management Strategies, Saba Irfan, Amanda Cantu

Research Colloquium

“Brittle diabetes” describes a form of diabetes marked by severe, unpredictable fluctuations in blood glucose, often leading to frequent episodes of hypoglycemia and hyperglycemia. Though not formally recognized by major diabetes organizations, the term is clinically useful, especially for vulnerable populations such as older adults with Type 1 Diabetes Mellitus (T1DM). Age-related factors—cognitive impairment, mobility limitations, dexterity issues, sensory decline, inconsistent eating habits, and frailty—make glycemic control particularly challenging and require a personalized, multidisciplinary management approach.

We report the case of a 66-year-old Hispanic female with long-standing T1DM, seizure disorder, and osteoporosis. Despite adherence to a prescribed insulin regimen, her …

The Sodium Chronicles: Unraveling The Enigma Of Hypothyroidism-Induced Hyponatremia, Raquel Z. Lara, Tejaswini Swamy, Jennifer Rojas Huen, Ricardo Serna

Research Colloquium

Background: Hyponatremia is an electrolyte disturbance with various etiologies, but hypothyroidism is rarely the primary cause. Literature suggests that hypothyroidism-related hyponatremia occurs primarily in severe cases, with some studies suggesting that hypothyroidism should not be considered a sole contributor if TSH levels are below 50 mIU/L. Patients with hyponatremia have a high risk of prolonged hospital stays and readmission, underscoring the clinical importance of identifying uncommon causes such as severe hypothyroidism. This case highlights this rare association, contributing to the existing limited literature.

Case Presentation: A 74-year-old woman with Type 2 Diabetes, complicated nephrotic syndrome and nephropathy, congestive heart failure, …

Comparison Of Cytology And Histology Diagnosis Methods In Metastatic Anaplastic Thyroid Cancer, Phyllis Yang, John Nicholas Cauba, Shizue Mito

Research Colloquium

Background: Anaplastic thyroid cancer (ATC) is a rare and extremely aggressive form of thyroid cancer that presents as a rapidly enlarging neck mass with compressive symptoms. Its malignancy and mortality rates approach nearly 90% and is a feared transformation of papillary thyroid cancer (PTC). A contributor to its increased mortality is its predilection for metastasis, which by nature, is less documented in medical literature. The study of ATC’s diagnostic algorithm, which classically utilizes cytological and histological confirmation, is crucial in enhancing early recognition and atypical presentations.

Methods: This systematic review catalogs the diagnosis, clinical properties, and metastasis sites of anaplastic …

Epac1 Deletion Attenuates Müller Glial Pathological Activation And Mitigates Retinal Neurodegeneration In Ischemia-Induced Retinopathy, Shuizhen Shi, Fan Xia, Zhongqiao Lu, Erick Palacios, Fang Mei, Massoud Motamedi, Xiaodong Cheng, Hua Liu, Wenbo Zhang

The Brown Foundation: Institute of Molecular Medicine

Introduction: Ischemia-induced retinopathies, such as retinopathy of prematurity and proliferative diabetic retinopathy, are major causes of vision loss. Both pathological neovascularization and neuronal damage contribute to vision impairment in these conditions, yet current therapies primarily target neovascularization and may further compromise neuronal health.

Objectives: Cyclic AMP (cAMP) is a widely recognized second messenger regulating diverse physiological and pathological processes. Exchange protein directly activated by cAMP (Epac) is a recently identified effector of cAMP signaling. This study aimed to investigate the role of Epac1 in ischemia-induced retinopathy and elucidate its underlying mechanisms using a mouse model of oxygen-induced retinopathy (OIR).

Methods: …

Amino Acids And Cart Distinguish A-Β+ Ketosis-Prone Diabetes From Type 1 And Type 2 Diabetes During Hyperglycemic Crises, Farook Jahoor, Jean W Hsu, Kelly R Keene, W Frank Peacock, Xiaofang Huang, Danielle Guffey, Jinyoung Byun, Rasmus Bennet, Ake Lernmark, Mustafa Tosur, Ashok Balasubramanyam

Children’s Nutrition Research Center Staff Publications

Context: When clinically stable, patients with A-β+ ketosis-prone diabetes (KPD) manifest unique markers of amino acid metabolism. Biomarkers differentiating KPD from type 1 (T1D) and type 2 diabetes (T2D) during hyperglycemic crises would accelerate diagnosis and management.

Objective: Compare serum metabolomics of KPD, T1D, and T2D patients during hyperglycemic crises, and utilize classification and regression tree (CART) modeling to distinguish these forms of diabetes.

Methods: At an urban hospital emergency center, adults with KPD, T1D, and T2D during hyperglycemic crises with or without diabetic ketoacidosis (DKA), and healthy controls, underwent comparisons of serum metabolite and hormonal profiles and CART analyses. …

Genome-Wide Insights Into The Genes And Pathways Shaping Human Foveal Development: Redefining The Genetic Landscape Of Foveal Hypoplasia, Callum Hunt, Ha-Jun Yoon, Alvin Lirio, Kayesha Coley, Jun Wang, Nick Shrine, Jianming Shao, Gail D E Maconachie, Zhanhan Tu, Jonathan H Zippin, Pirro G Hysi, Christopher J Hammond, Omar A Mahroo, Mariya Moosajee, Michel Michaelides, Andrew R Webster, Ala Moshiri, Rui Chen, Martin D Tobin, Chiara Batini, Mervyn G Thomas, Uk Biobank Eye And Vision Consortium

Faculty, Staff and Students Publications

Purpose: To define the genetic architecture of foveal morphology and explore its relevance to foveal hypoplasia (FH), a hallmark of developmental macular disorders.

Methods: We applied deep-learning algorithms to quantify foveal pit depth from central optical coherence tomography (OCT) B-scans in 61,269 UK Biobank participants. A genome-wide association study (GWAS) was conducted using REGENIE, adjusting for age, sex, height, and ancestry. Rare coding variants (frequency < 1%) were analyzed in an exome-wide rare-variant association study (RVAS). Candidate genes were prioritized using integrative mapping; pathway, cross-ancestry, and genetic-correlation analyses were exploratory.

Results: GWAS identified 126 sentinel variants, including 47 novel associations. Integrative mapping prioritized 129 putative causal genes, with 64 not previously implicated in foveal biology. Enriched pathways included retinoic acid metabolism (e.g., CYP26A1), photoreceptor differentiation …

Diagnostic Journey In The Recognition Of Oncogenic Osteomalacia, Steven B. Nagelberg, Mihaela Biscoveanu, Barbara Bix, Carrie Andrews, Srinivas Prasad

Jefferson Health - Northeast Papers (formerly Aria Health Papers)

A 73-year-old woman with a remote history of successfully treated primary hyperparathyroidism was referred to our office because of multiple skeletal fractures and proximal muscle weakness. Prior laboratory evaluation demonstrated hypocalcemia, vitamin D deficiency, elevated PTH, and elevated alkaline phosphatase. Updated evaluation in our clinic additionally showed hypophosphatemia prompting measurement of serum fibroblast growth factor 23 (FGF23). FGF23 proved to be markedly elevated prompting consideration of tumor-induced osteomalacia. Positron emission tomography with Cu-64 oxodotreotide revealed an enhancing focus in the left thoracic spine that was confirmed on magnetic resonance imaging to be a 1.5-cm extradural mass. The patient underwent surgical …

Synthetic Zfta Fusions Pinpoint Disordered Protein Domain Acquisition As A Mechanism Of Brain Tumorigenesis, A Arabzade, H K Shirnekhi, S Varadharajan, S M Ippagunta, A H Phillips, N Laboe, D W Baggett, Wahiduzzaman, M Jo, T Zheng, R Pathak, D Gee, D Bhimsaria, H Wu, X Gao, J Liu, E Emanus, A Bland, A Kardian, A Hancock, B Holcomb, T Wright, T Bugbee, H Sun, M Zhai, E Caesar, M Park, S Tripathi, A Shirinifard, K Lowe, A Khalighifar, R A Petersen, S King, D Stabley, A Pitre, G E Campbell, C-G Park, W T Freyaldenhoven, B Chandra, Y Xia, E Bonten, A Achari, S Kandikonda, A Carisey, S B Pounds, J Xu, D W Ellison, B Deneen, K C Bertrand, R W Kriwacki, S C Mack

Children’s Nutrition Research Center Staff Publications

Over 95% of ependymomas that arise in the cortex are driven by a gene fusion involving the zinc finger translocation-associated (ZFTA) protein. Here, using super-resolution and lattice light-sheet microscopy, we demonstrate that the most frequent fusion variant, ZFTA-RELA (ZR), forms dynamic nuclear condensates that are required for oncogene expression and tumorigenesis. Mutagenesis studies of ZR reveal a key intrinsically disordered region (IDR) in RELA that governs condensate formation. Condensate-modulating IDR mutations introduced into ZR impaired its genomic occupancy at oncogenic loci and inhibited the recruitment of transcriptional effector proteins, such as MED1, BRD4 and RNA polymerase II. Using nuclear magnetic …

A Consensus Guide To Preclinical Indirect Calorimetry Experiments, Alexander S Banks, David B Allison, Thierry Alquier, Ansarullah, Steven N Austad, Johan Auwerx, Julio E Ayala, Joseph A Baur, Stefania Carobbio, Gary A Churchill, Morten Dall, Rafael De Cabo, Jose Donato, Nathalia R V Dragano, Carol F Elias, Anthony W Ferrante, Brian N Finck, Jose E Galgani, Zachary Gerhart-Hines, Laurie J Goodyear, Justin L Grobe, Rana K Gupta, Kirk M Habegger, Sean M Hartig, Andrea L Hevener, Steven B Heymsfield, Corey D Holman, Martin Hrabě De Angelis, David E James, Lawrence Kazak, Jae Bum Kim, Martin Klingenspor, Xingxing Kong, Sander Kooijman, Louise Lantier, K C Kent Lloyd, James C Lo, Irfan J Lodhi, Paul S Maclean, Owen P Mcguinness, Gema Medina-Gómez, Raghavendra G Mirmira, Christopher D Morrison, Gregory J Morton, Timo D Müller, Yoshihiro Ogawa, David Pajuelo-Reguera, Matthew J Potthoff, Nathan Qi, Marc L Reitman, Patrick C N Rensen, Jan Rozman, Jennifer M Rutkowsky, Kei Sakamoto, Philipp E Scherer, Gary J Schwartz, Radislav Sedlacek, Mohammed Selloum, Saame Raza Shaikh, Shuai Chen, Gerald I Shulman, Vojtěch Škop, Alexander A Soukas, John R Speakman, Bruce M Spiegelman, Gregory R Steinberg, Katrin J Svensson, John P Thyfault, Tony Tiganis, Paul M Titchenell, Nigel Turner, Licio A Velloso, Antonio Vidal-Puig, Christopher S Ward, Ashley S Williams, Christian Wolfrum, Allison W Xu, Ying Xu, Juleen R Zierath, International Indirect Calorimetry Consensus Committee (Iiccc)

Children’s Nutrition Research Center Staff Publications

Understanding the complex factors influencing mammalian metabolism and body weight homeostasis is a long-standing challenge requiring knowledge of energy intake, absorption and expenditure. Using measurements of respiratory gas exchange, indirect calorimetry can provide non-invasive estimates of whole-body energy expenditure. However, inconsistent measurement units and flawed data normalization methods have slowed progress in this field. This guide aims to establish consensus standards to unify indirect calorimetry experiments and their analysis for more consistent, meaningful and reproducible results. By establishing community-driven standards, we hope to facilitate data comparison across research datasets. This advance will allow the creation of an in-depth, machine-readable data …

Randomized Trial: Peppermint Oil (Menthol) Pharmacokinetics In Children And Effects On Gut Motility In Children With Functional Abdominal Pain: 540 Mg Vs. 900 Mg Dose Comparison, Robert J Shulman, Bruno P Chumpitazi, Daniel Gonzalez, Uttam Garg, Salma Musaad, Jiali Wen, Gregory L Kearns

Children’s Nutrition Research Center Staff Publications

Aims: There is a paucity of information on the pharmacokinetics (PK) and pharmacodynamics (PD) of menthol, the active ingredient in peppermint oil (PMO). We studied the PK of menthol (540 and 900 mg) in children and measured their effects on gut transit/contractility.

Methods: Children 7-12 years of age with functional abdominal pain underwent wireless motility capsule (WMC) testing. One week later, they were randomized to 540 mg or 900 mg of oral enteric-coated PMO. Blood was sampled over 24 h to determine menthol PK. The WMC test was repeated while they took their respective dose (180 mg thrice or 180 …

The Potential Of 4-Methylumbelliferone To Be Repurposed For Treating Liver Fibrosis, Xi Chen, Huiqiao Li, Yanru Deng, Jieyi Meng, Shangang Zhao, Clavia Ruth Wooton-Kee, Xia Gao, Bingning Dong, Dongyin Guan, Chaodong Wu, Philipp E Scherer, Yi Zhu

Faculty, Staff and Students Publications

4-Methylumbelliferone (4-MU) is the active component of hymecromone, a choleretic and antispasmodic drug with an excellent safety profile. In rodent studies, high doses of 4-MU are also used to inhibit the production of hyaluronan (HA), a biomarker of liver fibrosis. Further, 4-MU shows excellent efficacy in inhibiting liver fibrosis of different etiologies in animal studies, eliciting interest in its repurposing for this condition. However, 4-MU's mechanism of action, and whether it inhibits liver fibrosis by impeding HA synthesis remains unclear. Using several transgenic mouse models with HA overproduction or degradation in different types of liver cells, we found that both …

Time-Frequency Fingerprint Analysis In Seeg Source-Space To Identify The Epileptogenic Zone, Yash Shashank Vakilna, Deniz Atilgan, Johnson Hampson, Chinmay Chinara, Takfarinas Medani, Richard M Leahy, Nuria Lacuey, Samden D Lhatoo, Sandipan Pati, John C Mosher, Jay R Gavvala

Faculty, Staff and Student Publications

This case study highlights the application of seizure fingerprint analysis in the source-space of stereo-EEG (SEEG) data to accurately localize the epileptogenic zone (EZ) in patients with complex cortical malformations. A 25-year-old female with extensive bilateral perisylvian polymicrogyria (PMG) presented with intractable focal seizures. The source-level analysis performed in Brainstorm using the sLORETA imaging algorithm subsequently showed EZ fingerprint analysis. The patient underwent MR-guided laser interstitial thermal therapy (LITT), targeting the identified EZ, resulting in postoperative seizure freedom with minimal complications. Extending the analysis from the sensor-space to the source-space could further enhance surgical planning and improve outcomes in complex …

A Case Of Adrenal Insufficiency Presenting With Seizures, Complicated By Developmental Cerebral Venous Anomaly And Takotsubo Cardiomyopathy: A Case Report, Katrina Villegas, Brittany Eason, Karolina Janiec, Alaa Musallam, Ahmed Hammouda, Samia Ammar Aldwaik, Radhika Tailor

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Adrenal insufficiency is a potentially life-threatening condition that often presents with nonspecific symptoms. While fatigue, hypotension, and electrolyte disturbances are common features, seizures and stress-induced cardiomyopathy are rare initial manifestations. This case is reported for its atypical presentation and to highlight the diagnostic challenge it posed in the absence of classic biochemical findings.

CASE PRESENTATION: We report a case of a 68-year-old Hispanic woman with diabetes, hypertension, dyslipidemia, and hypopituitarism secondary to Sheehan syndrome, who presented with new-onset seizures after abruptly discontinuing chronic steroid therapy. Her symptoms included progressive weakness and behavioral changes over several weeks. Initial evaluation revealed …

The Impact Of Different Antidiabetic Drugs On Fracture Risk In Patients With Type 2 Diabetes Mellitus: A Systematic Review And Network Meta-Analysis Of Randomized Controlled Trials With A Focus On Sglt2 Inhibitors, Bushra Admani, Fizza Z. Raza, Fatima Siddiqui, Muhammad T. Ashraf, Muhammad K. Khan, Ifra Habib, Ayesha Usman, Bareeha Mansoor, Zaira Nadeem, Rana J. Ghaffer, Muhammad Riyyan, Sawaira Sajid, Muhammad H. A. Chania, Mahnoor Saleem, Saad Javaid, Nikhil Duseja, Hussam Al Hennawi, Sunita Lakhani

Abington Jefferson Health Papers

SGLT2 inhibitors are a new class of antidiabetic drugs that have shown cardiovascular benefits in patients with type 2 diabetes mellitus (T2DM) and cardiovascular disease. However, their effects on fracture risk are unclear and may depend on the type and duration of treatment. This meta-analysis compares the fracture risk of different antidiabetic drugs, including SGLT2 inhibitors, based on data from randomized controlled trials (RCTs). We searched 4 databases for RCTs that reported fracture events in patients with T2DM who received different antidiabetic drugs. We included 117 RCTs that compared 9 types of antidiabetic drugs: SGLT2 inhibitors, DPP-4 inhibitors, α-glucosidase inhibitors, …

Proteomics-Based Aging Clocks In Midlife Or Late-Life And Their Associated Risk Of Dementia, Sanaz Sedaghat, Saeun Park, Rob F Walker, Shuo Wang, Jialing Liu, Timothy M Hughes, Behnam Sabayan, Weihong Tang, Josef Coresh, James S Pankow, Keenan A Walker, Ramon Casanova, Ruth Dubin, Rajat Deo, Jerome I Rotter, Alexis C Wood, Peter Ganz, Pamela L Lutsey, Weihua Guan, Anna Prizment

Children’s Nutrition Research Center Staff Publications

Background: Biological age can be quantified by composite proteomic scores, called proteomics-based aging clocks (PACs). We investigated whether a discrepancy between chronological and biological age in midlife and late-life is associated with cognition and dementia risk.

Methods: We used two longitudinal population-based studies: the Atherosclerosis Risk in Communities (ARIC) Study and the Multi-Ethnic Study of Atherosclerosis (MESA). PACs were created in ARIC at midlife (mean age: 58 years, 57% female, n = 11,758) and late-life (mean age: 77 years, 56% female, n = 4934) using elastic net regression models in two-thirds of dementia-free participants and validated in the remaining one-third …

Polo-Like Kinase 1 Inactivation Enhances Pi3k Inhibition-Mediated Apoptosis Of Notch1-Mutant Head And Neck Squamous Cell Carcinoma, Pooja A Shah, Tuhina Mazumdar, Soma Ghosh, Lacin Yapindi, Reid T Powell, Yong S Park, Li Shen, Anne M Fernandez, Clifford C Stephan, Jing Wang, Andrew G Sikora, Jawad Kazi, Mitchell J Frederick, Faye M Johnson

Children’s Nutrition Research Center Staff Publications

PI3K inhibition causes apoptosis selectively in NOTCH1-mutant head and neck squamous cell carcinoma (HNSCC), but modest single-agent responses and acquired resistance (AR) limit the clinical efficacy of targeted agents. To address these limitations, we investigated novel combination therapies. We tested the efficacy of 5768 compounds as single agents and 139 in combination with PI3K inhibitors in sensitive and AR NOTCH1-mutant HNSCC cell lines. We generated synergy/efficacy classifications for the combinations using multiple metrics of statistical drug synergy and growth rate indices. The PLK1/PI3K combination's efficacy was validated using orthogonal in vitro methods and in two HNSCC xenograft models. Compound efficacy …