Digital Commons Network^™

Dietary Folate And Cofactors Accelerate Age-Dependent P16 Epimutation To Promote Intestinal Tumorigenesis, Li Yang, Robert C Peery, Leah M Farmer, Xia Gao, Yiqun Zhang, Chad J Creighton, Lanjing Zhang, Lanlan Shen

Faculty, Staff and Students Publications

The extent to which non-genetic environmental factors, such as diet, contribute to carcinogenesis has been long debated. One potential mechanism for the effects of environmental factors is through epigenetic modifications that affect gene expression without changing the underlying DNA sequence. However, the functional cooperation between dietary factors and cancer-causing epigenetic regulation is largely unknown. Here, we use a mouse model of age-dependent p16 epimutation, in which the p16 gene activity is directly controlled by promoter DNA methylation. We show p16 epimutation is modulated by folate and cofactors in dietary supplementation, which leads to increased colon cancer risk. Importantly, our findings …

The Geriatric Nutritional Risk Index As A Predictor Of Complications In Geriatric Trauma Patients, Daniel H Wang, Yoko Fujita, Antonio Dono, Ana G Rodriguez Armendariz, Mauli Shah, Nagireddy Putluri, Pavel S Pichardo-Rojas, Chirag B Patel, Jay-Jiguang Zhu, Jason T Huse, Brittany C Parker Kerrigan, Frederick F Lang, Yoshua Esquenazi, Leomar Y Ballester

Faculty, Staff and Student Publications

Cerebrospinal fluid (CSF) analysis is underutilized in patients with glioblastoma (GBM), partly due to a lack of studies demonstrating the clinical utility of CSF biomarkers. While some studies show the utility of CSF cell-free DNA analysis, studies analyzing CSF metabolites in patients with glioblastoma are limited. Diffuse gliomas have altered cellular metabolism. For example, mutations in isocitrate dehydrogenase enzymes (e.g., IDH1 and IDH2) are common in diffuse gliomas and lead to increased levels of D-2-hydroxyglutarate in CSF. However, there is a poor understanding of changes CSF metabolites in GBM patients. In this study, we performed targeted metabolomic analysis of CSF …

Organelle Proteomic Profiling Reveals Lysosomal Heterogeneity In Association With Longevity, Yong Yu, Shihong M Gao, Youchen Guan, Pei-Wen Hu, Qinghao Zhang, Jiaming Liu, Bentian Jing, Qian Zhao, David M Sabatini, Monther Abu-Remaileh, Sung Yun Jung, Meng C Wang

Faculty, Staff and Students Publications

Lysosomes are active sites to integrate cellular metabolism and signal transduction. A collection of proteins associated with the lysosome mediate these metabolic and signaling functions. Both lysosomal metabolism and lysosomal signaling have been linked to longevity regulation; however, how lysosomes adjust their protein composition to accommodate this regulation remains unclear. Using deep proteomic profiling, we systemically profiled lysosome-associated proteins linked with four different longevity mechanisms. We discovered the lysosomal recruitment of AMP-activated protein kinase and nucleoporin proteins and their requirements for longevity in response to increased lysosomal lipolysis. Through comparative proteomic analyses of lysosomes from different tissues and labeled with …

Advancements In Revascularization Strategies For Acute Mesenteric Ischemia: A Comprehensive Review, Jacob J Gries, Hafeez Ul Hassan Virk, Bing Chen, Takashi Sakamoto, Mahboob Alam, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Even with modern advancements in the management of acute mesenteric ischemia over the past decade, morbidity and mortality remain high, and the best primary treatment modality is still debated amongst interventionalists. Traditionally, interventionalists have favored an open surgical approach but are now trending for endovascular interventions due to apparent reduced mortality and complications. Newer studies suggest hybrid approaches, and intestinal stroke centers may be superior to either strategy alone. This narrative review will explore the natural history of acute mesenteric ischemia with the aim of increasing interventionalist awareness of modern advancements in revascularization strategies for this devastating disease.

Impact Of Left Ventricular Assist Devices On 30-Day Readmission And Outcomes In Non-Variceal Upper Gastrointestinal Bleeding: A Nationwide Analysis, Umer Farooq, Zahid Ijaz Tarar, Adnan Malik, Muhammad Kashif Amin, Mustafa Gandhi, Moosa Tarar, Faisal Kamal

Division of Gastroenterology and Hepatology Faculty Papers

INTRODUCTION: Bleeding, especially non-variceal upper gastrointestinal bleeding (NVUGIB), remains the most common cause of readmission in left ventricular assist device (LVAD) patients. Any readmission after NVUGIB carries a worse prognosis.

AIM: To compare readmission outcomes in NVUGIB patients with and without LVAD.

MATERIAL AND METHODS: We identified adult NVUGIB patients using the National Readmission Database 2018 employing International Classification of Diseases, Tenth Revision (ICD-10) codes. The patients were grouped based on LVAD history. Proportions were compared using the Fisher exact test, and multivariate Cox proportional regression analysis was used to compute adjusted

RESULTS: The analysis included 322,342 NVUGIB patients, 1403 …

Deep Learning-Based Multimodality Classification Of Chronic Mild Traumatic Brain Injury Using Resting-State Functional Mri And Pet Imaging, Faezeh Vedaei, Najmeh Mashhadi, Mahdi Alizadeh, George Zabrecky, Daniel A. Monti, Md, Nancy Wintering, Emily Navarreto, Chloe Hriso, Andrew B. Newberg, Feroze B. Mohamed

Department of Radiology Faculty Papers

Mild traumatic brain injury (mTBI) is a public health concern. The present study aimed to develop an automatic classifier to distinguish between patients with chronic mTBI (n = 83) and healthy controls (HCs) (n = 40). Resting-state functional MRI (rs-fMRI) and positron emission tomography (PET) imaging were acquired from the subjects. We proposed a novel deep-learning-based framework, including an autoencoder (AE), to extract high-level latent and rectified linear unit (ReLU) and sigmoid activation functions. Single and multimodality algorithms integrating multiple rs-fMRI metrics and PET data were developed. We hypothesized that combining different imaging modalities provides complementary information and …

Complementary And Integrative Health Information In The Literature: Its Lexicon And Named Entity Recognition, Huixue Zhou, Robin Austin, Sheng-Chieh Lu, Greg Marc Silverman, Yuqi Zhou, Halil Kilicoglu, Hua Xu, Rui Zhang

Faculty, Staff and Student Publications

Objective: To construct an exhaustive Complementary and Integrative Health (CIH) Lexicon (CIHLex) to help better represent the often underrepresented physical and psychological CIH approaches in standard terminologies, and to also apply state-of-the-art natural language processing (NLP) techniques to help recognize them in the biomedical literature.

Materials and methods: We constructed the CIHLex by integrating various resources, compiling and integrating data from biomedical literature and relevant sources of knowledge. The Lexicon encompasses 724 unique concepts with 885 corresponding unique terms. We matched these concepts to the Unified Medical Language System (UMLS), and we developed and utilized BERT models comparing their efficiency …

Treatment Effects Of N-Acetyl Cysteine On Resting-State Functional Mri And Cognitive Performance In Patients With Chronic Mild Traumatic Brain Injury: A Longitudinal Study, Faezeh Vedaei, Andrew B. Newberg, M. Alizadeh, George Zabrecky, Emily Navarreto, Chloe Hriso, Nancy Wintering, Feroze Mohamed, Daniel A. Monti

Marcus Institute of Integrative Health Faculty Papers

Mild traumatic brain injury (mTBI) is a significant public health concern, specially characterized by a complex pattern of abnormal neural activity and functional connectivity. It is often associated with a broad spectrum of short-term and long-term cognitive and behavioral symptoms including memory dysfunction, headache, and balance difficulties. Furthermore, there is evidence that oxidative stress significantly contributes to these symptoms and neurophysiological changes. The purpose of this study was to assess the effect of N-acetylcysteine (NAC) on brain function and chronic symptoms in mTBI patients. Fifty patients diagnosed with chronic mTBI participated in this study. They were categorized into two groups …

Disruption Of The Arabidopsis Acyl-Activating Enzyme 3 Impairs Seed Coat Mucilage Accumulation And Seed Germination, Ninghui Cheng, Paul A Nakata

Faculty, Staff and Students Publications

The Acyl-activating enzyme (AAE) 3 gene encodes an oxalyl-CoA synthetase that catalyzes the conversion of oxalate to oxalyl-CoA as the first step in the CoA-dependent pathway of oxalate catabolism. Although the role of this enzyme in oxalate catabolism has been established, its biological roles in plant growth and development are less understood. As a step toward gaining a better understanding of these biological roles, we report here a characterization of the Arabidopsis thaliana aae3 (Ataae3) seed mucilage phenotype. Ruthidium red (RR) staining of Ataae3 and wild type (WT) seeds suggested that the observed reduction in Ataae3 …

Development And Validation Of A Nomogram For Predicting Pulmonary Infection In Patients Receiving Immunosuppressive Drugs, Chuxuan Luo, Yue Zhang, Jiajie Zhang, Chen Jin, Xiaolan Ye, Yan Ren, Huajuan Shen, Maosheng Chen, Yiwen Li, Qiang He, Guangbiao Xu, Lina Shao

Faculty, Staff and Student Publications

Objective: Pulmonary infection (PI), a severe complication of immunosuppressive therapy, affects patients' prognosis. As part of this study, we aimed to construct a pulmonary infection prediction (PIP) model and validate it in patients receiving immunosuppressive drugs (ISDs). Methods: Totally, 7,977 patients being treated with ISDs were randomised 7:3 to the developing (n = 5,583) versus validation datasets (n = 2,394). Our predictive nomogram was established using the least absolute shrinkage and selection operator (LASSO) and multivariate COX regression analyses. With the use of the concordance index (C-index) and calibration curve, the prediction performance of the final model was …

Gad65abs Are Not Associated With Beta-Cell Dysfunction In Patients With T2d In The Grade Study, Christiane S Hampe, Ali Shojaie, Barbara Brooks-Worrell, Sepideh Dibay, Kristina Utzschneider, Steven E Kahn, Mary E Larkin, Mary L Johnson, Naji Younes, Neda Rasouli, Cyrus Desouza, Robert M Cohen, Jean Y Park, Hermes J Florez, Willy Marcos Valencia, Robert Stempel, Jerry P Palmer, Ashok Balasubramanyam

Faculty, Staff and Students Publications

CONTEXT: Autoantibodies directed against the 65-kilodalton isoform of glutamic acid decarboxylase (GAD65Abs) are markers of autoimmune type 1 diabetes (T1D) but are also present in patients with Latent Autoimmune Diabetes of Adults and autoimmune neuromuscular diseases, and also in healthy individuals. Phenotypic differences between these conditions are reflected in epitope-specific GAD65Abs and anti-idiotypic antibodies (anti-Id) against GAD65Abs. We previously reported that 7.8% of T2D patients in the GRADE study have GAD65Abs but found that GAD65Ab positivity was not correlated with beta-cell function, glycated hemoglobin (HbA1c), or fasting glucose levels.

CONTEXT: In this study, we aimed to better characterize islet autoantibodies …

Chemical Catalysis Guides Structural Identification For The Major In Vivo Metabolite Of The Bet Inhibitor Jq1, Secondra Holmes, Prashi Jain, Kenneth Guzman Rodriguez, Jade Williams, Zhifeng Yu, Christian Cerda-Smith, Errol L G Samuel, James Campbell, John Michael Hakenjos, Diana Monsivais, Feng Li, Srinivas Chamakuri, Martin M Matzuk, Conrad Santini, Kevin R Mackenzie, Damian W Young

Faculty, Staff and Students Publications

The bromodomain inhibitor (+)-JQ1 is a highly validated chemical probe; however, it exhibits poor in vivo pharmacokinetics. To guide efforts toward improving its pharmacological properties, we identified the (+)-JQ1 primary metabolite using chemical catalysis methods. Treatment of (+)-JQ1 with tetrabutylammonium decatungstate under photochemical conditions resulted in selective formation of an aldehyde at the 2-position of the thiophene ring [(+)-JQ1-CHO], which was further reduced to the 2-hydroxymethyl analog [(+)-JQ1-OH]. Comparative LC/MS analysis of (+)-JQ1-OH to the product obtained from liver microsomes suggested (+)-JQ1-OH as the major metabolite of (+)-JQ1. The 2-thienyl position was then substituted to generate a trideuterated (−CD3, (+)-JQ1-D) …

Barriers To Care For Children With Cerebral Palsy In The Rural State Of Maine: A Mixed-Methods Study, Rayne L. Whitten, Anya K. Cutler, Alexa K. Craig

Journal of Maine Medical Center

Introduction: Guidelines on orthopedic hip surveillance in children with cerebral palsy have been published to minimize the effects of cerebral palsy and maximize quality of life. Researchers aimed to identify barriers to cerebral palsy care and to assess adherence to national hip-surveillance guidelines among a small subset of children with cerebral palsy who live in a rural state.

Methods: Parents of children with cerebral palsy were interviewed, and thematic analyses were performed on the recorded transcripts. Patient-specific data about imaging and demographics were manually extracted from the electronic health record to perform a mixed-methods analysis.

Results: Twenty-one parents were interviewed, …

Antibiotic-Induced Gut Dysbiosis Elicits Gut-Brain Axis Relevant Multi-Omic Signatures And Behavioral And Neuroendocrine Changes In A Nonhuman Primate Model, Shivdeep S. Hayer, Mackenzie Conrin, Jeffrey French, Andrew K. Benson, Sophie Alvarez, Kathryn Dempsey, Anne Fischer, Zahraa Wajih Alsafwani, William Gasper, Mallory J. Suhr Van Haute, Haley R. Hassenstab, Shayda Azadmanesh, Missy Briardy, Skyler Gerbers, Aliyah Jabenis, Jennifer L. Thompson, Jonathan B. Clayton

Food for Health: Publications

Emerging evidence indicates that antibiotic-induced dysbiosis can play an etiological role in the pathogenesis of neuropsychiatric disorders. However, most of this evidence comes from rodent models. The objective of this study was to evaluate if antibiotic-induced gut dysbiosis can elicit changes in gut metabolites and behavior indicative of gut-brain axis disruption in common marmosets (Callithrix jacchus) – a nonhuman primate model often used to study sociability and stress. We were able to successfully induce dysbiosis in marmosets using a custom antibiotic cocktail (vancomycin, enrofloxacin and neomycin) administered orally for 28 days. This gut dysbiosis altered gut metabolite profiles, …

Regional Variability In The Prevalence Of Food Insecurity And Diet Quality Among United States Children, Jayna M Dave, Tzuan A Chen, Alexandra N Castro, Mamie White, Elizabeth A Onugha, Sloane Zimmerman, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Understanding the association between food security status (FSS) and diet quality in children is crucial. This study investigated regional variability in FSS, participation in the federal nutrition assistance program (FNAP), and diet quality among US children. National Health and Nutrition Examination Survey (NHANES) data from 2013 to 2016 were analyzed. The association between FSS, FNAP participation, and diet quality (Healthy Eating Index—HEI-2015) was assessed using multiple linear/logistic regression models. The sample included 6403 children (mean age: 7.5 years; 51% male; 33% Hispanic). Within the sample, 13% reported child food insecurity, and 30% reported household food insecurity. Additionally, 90% participated in …

Editorial: Care During Pregnancy And Early Childhood For Growth And Development In Low- And Middle- Income Countries, Ranadip Chowdhury, Ravi Prakash Upadhyay, Bireshwar Sinha, Nita Bhandari, Sunita Taneja, Jai K. Das

Centre of Excellence in Women and Child Health

No abstract provided.

Tfeb Drives Mtorc1 Hyperactivation And Kidney Disease In Tuberous Sclerosis Complex, Nicola Alesi, Damir Khabibullin, Dean M Rosenthal, Elie W Akl, Pieter M Cory, Michel Alchoueiry, Samer Salem, Melissa Daou, William F Gibbons, Jennifer A Chen, Long Zhang, Harilaos Filippakis, Laura Graciotti, Caterina Miceli, Jlenia Monfregola, Claudia Vilardo, Manrico Morroni, Chiara Di Malta, Gennaro Napolitano, Andrea Ballabio, Elizabeth P Henske

Duncan NRI Faculty and Staff Publications

Tuberous Sclerosis Complex (TSC) is caused by TSC1 or TSC2 mutations, leading to hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) and lesions in multiple organs including lung (lymphangioleiomyomatosis) and kidney (angiomyolipoma and renal cell carcinoma). Previously, we found that TFEB is constitutively active in TSC. Here, we generated two mouse models of TSC in which kidney pathology is the primary phenotype. Knockout of TFEB rescues kidney pathology and overall survival, indicating that TFEB is the primary driver of renal disease in TSC. Importantly, increased mTORC1 activity in the TSC2 knockout kidneys is normalized by TFEB knockout. In TSC2-deficient …

N-Acetylaspartate From Fat Cells Regulates Postprandial Body Temperature, Jessica B Felix, Pradip K Saha, Evelyn De Groot, Lin Tan, Robert Sharp, Elizabeth S Anaya, Yafang Li, Holly Quang, Nooshin Saidi, Layla Abushamat, Christie M Ballantyne, Christopher I Amos, Philip L Lorenzi, Samuel Klein, Xia Gao, Sean M Hartig

Faculty, Staff and Students Publications

N-acetylaspartate (NAA), the brain’s second most abundant metabolite, provides essential substrates for myelination through its hydrolysis. However, activities and physiological roles of NAA in other tissues remain unknown. Here, we show aspartoacylase (ASPA) expression in white adipose tissue (WAT) governs systemic NAA levels for postprandial body temperature regulation. Proteomics and mass spectrometry revealed NAA accumulation in WAT of Aspa knockout mice stimulated the pentose phosphate pathway and pyrimidine production. Stable isotope tracing confirmed higher incorporation of glucose-derived carbon into pyrimidine metabolites in Aspa knockout cells. Additionally, serum NAA positively correlates with the pyrimidine intermediate orotidine and this relationship predicted lower …

Comparison Of Energy Budget Of Cockroach Nymph (Hemimetabolous) And Hornworm (Holometabolous) Under Food Restriction, Charles J Green, Chen Hou

Faculty, Staff and Student Publications

Animals with different life histories budget their intake energy differently when food availability is low. It has been shown previously that hornworm (larva of Manduca sexta), a holometabolous insect species with a short development stage, prioritizes growth at the price of metabolism under food restriction, but it is unclear how hemimetabolous insect species with a relatively long development period budget their intake energy under food scarcity. Here, we use orange head cockroaches (Eublaberus posticus) to investigate this question. We found that for both species under food restriction, rates of metabolism and growth were suppressed, but the degree …

Open-Label Extension Of A Randomized Trial Investigating Safety And Efficacy Of Rhpth(1-84) In Hypoparathyroidism, Aliya A. Khan, Lisa G. Abbott, Intekhab Ahmed, Olulade Ayodele, Claudia Gagnon, Richard D. Finkelman, Emese Mezosi, Lars Rejnmark, Istvan Takacs, Shaoming Yin, Steven W. Ing

Division of Endocrinology, Diabetes and Metabolic Diseases Faculty Papers

Hypoparathyroidism (HypoPT) is a rare disease, often inadequately controlled by conventional treatment. PARALLAX was a mandatory post-marketing trial assessing pharmacokinetics and pharmacodynamics of different dosing regimens of recombinant human parathyroid hormone 1-84 (rhPTH[1-84]) for treating HypoPT. The present study (NCT03364738) was a phase 4, 1-yr open-label extension of PARALLAX. Patients received only 2 doses of rhPTH(1-84) in PARALLAX and were considered treatment-naive at the start of the current study. rhPTH(1-84) was initiated at 50 μg once daily, with doses adjusted based on albumin-corrected serum calcium levels. Albumin-corrected serum calcium (primary outcome measure), health-related quality of life (HRQoL), adverse events, and …

Impact Of Elexacaftor/Tezacaftor/Ivacaftor On Lipid And Fat‐Soluble Vitamin Levels And Association With Body Mass Index, Tanvi Patel, Kimberly Mcbennett, Senthilkumar Sankararaman, Teresa Schindler, Nori Mercuri Minich, Katherine Kutney

Faculty Scholarship

Introduction:Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve gastrointestinal absorption of nutrients and may result in changes in body mass index (BMI), serum lipids, and fat-soluble vitamin levels. We hypothesized that serum lipids and vitamin levels would increase with CFTR modulator therapy and that greater increase in lipids and vitamin levels would be related to greater increase in BMI. Methods:A retrospective study was performed to evaluate the impact of elexacaftor/tezacaftor/ivacaftor (ETI) on nutritional parameters, serum lipids, and fat-soluble vitamin levels. Pre-ETI values (<2 years prior) and post-ETI values (>1 month after) were compared. Linear regression was used to evaluate whether change in BMI is associated …

Alzheimer’S Disease And Microorganisms: The Non-Coding Rnas Crosstalk, Hanieh Mohammadi-Pilehdarboni, Mohammad Shenagari, Farahnaz Joukar, Hamed Naziri, Fariborz Mansour-Ghanaei

Department of Neurology Faculty Papers

Alzheimer’s disease (AD) is a complex, multifactorial disorder, influenced by a multitude of variables ranging from genetic factors, age, and head injuries to vascular diseases, infections, and various other environmental and demographic determinants. Among the environmental factors, the role of the microbiome in the genesis of neurodegenerative disorders (NDs) is gaining increased recognition. This paradigm shift is substantiated by an extensive body of scientific literature, which underscores the significant contributions of microorganisms, encompassing viruses and gut-derived bacteria, to the pathogenesis of AD. The mechanism by which microbial infection exerts its influence on AD hinges primarily on inflammation. Neuroinflammation, activated in …

Identifying Opportunities For Prevention Of Adverse Outcomes Following Female Genital Fistula Repair: Protocol For A Mixed-Methods Study In Uganda, Alison El Ayadi, Susan Obore, Fred Kirya, Suellen Miller, Abner Korn, Hadija Nalubwama, John Neuhaus, Monica Getahun, Patrick Eyul, Robert Twine, Erin Andrew, Justus Barageine

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Female genital fistula is a traumatic debilitating injury, frequently caused by prolonged obstructed labor, affecting between 500,000-2 million women in lower-resource settings. Vesicovaginal fistula causes urinary incontinence, and other morbidity may occur during fistula development. Women with fistula are stigmatized, limit social and economic engagement, and experience psychiatric morbidity. Improved surgical access has reduced fistula consequences yet post-repair risks impacting quality of life and well-being include fistula repair breakdown or recurrence and ongoing or changing urine leakage or incontinence. Limited evidence on risk factors contributing to adverse outcomes hinders interventions to mitigate adverse events. This study aims to quantify …

Contributions Of The Microbiome-Derived Metabolome For Risk Assessment And Prognostication Of Pancreatic Cancer, Ricardo A León-Letelier, Rongzhang Dou, Jody Vykoukal, Michele T Yip-Schneider, Anirban Maitra, Ehsan Irajizad, Ranran Wu, Jennifer B Dennison, Kim-An Do, Jianjun Zhang, C Max Schmidt, Samir Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

Background: Increasing evidence implicates microbiome involvement in the development and progression of pancreatic ductal adenocarcinoma (PDAC). Studies suggest that reflux of gut or oral microbiota can lead to colonization in the pancreas, resulting in dysbiosis that culminates in release of microbial toxins and metabolites that potentiate an inflammatory response and increase susceptibility to PDAC. Moreover, microbe-derived metabolites can exert direct effector functions on precursors and cancer cells, as well as other cell types, to either promote or attenuate tumor development and modulate treatment response.

Content: The occurrence of microbial metabolites in biofluids thereby enables risk assessment and prognostication of PDAC, …

Postprandial Glucose Variability Following Typical Meals In Youth Living With Type 1 Diabetes., Susana R. Patton, Simon Bergford, Jennifer L. Sherr, Robin L. Gal, Peter Calhoun, Mark A. Clements, Michael C. Riddell, Corby K. Martin

Manuscripts, Articles, Book Chapters and Other Papers

We explored the association between macronutrient intake and postprandial glucose variability in a large sample of youth living with T1D and consuming free-living meals. In the Type 1 Diabetes Exercise Initiative Pediatric (T1DEXIP) Study, youth took photographs before and after their meals on 3 days during a 10 day observation period. We used the remote food photograph method to obtain the macronutrient content of youth's meals. We also collected physical activity, continuous glucose monitoring, and insulin use data. We measured glycemic variability using standard deviation (SD) and coefficient of variation (CV) of glucose for up to 3 h after meals. …

Efficacy And Safety Of Once-Weekly Insulin Regimes On Glycemic Control For Type 2 Diabetes: A Systematic Review And Network Meta-Analysis, Peng Wang, Yu Zhang, Wenhao Xu, Liyuan Peng, Ping Xu, Weelic Chong, Yang Hai, Lu Jia, Fang Fang

Student Papers, Posters & Projects

Background

Randomized controlled trials have found that once-weekly insulin resulted in greater glycemic control compared to once-daily insulin in patients with type 2 diabetes. However, no direct comparisons have been made between different types of once-weekly insulin thus far. This systematic review and network meta-analysis aimed to evaluate the effect of the two most advanced once-weekly insulin analogues, namely insulin icodec and insulin Fc, in patients with type 2 diabetes.

Methods

We conducted a thorough search in the databases PubMed, Embase, and the Cochrane Central Register of Controlled Trials. The search included articles published from the beginning to October 10, …

Infant Growth And Body Composition From Birth To 24 Months: Are Infants Developing The Same?, Shane A. Norris, Lukhanyo H. Nyati, Alexia Murphy Alford, Nishani Lucas, Ina S. Santos, Caroline S. Costa, Rebecca Kuriyan, V Pujitha Wickranasinghe, Shabina Ariff, Andrew P. Hills

Department of Paediatrics and Child Health

Background: Given the importance of infancy for establishing growth trajectories, with later-life health consequences, we investigated longitudinal body composition among infants from six economically and ethnically diverse countries.
Methods: We recruited mother-infant dyads using the WHO Multicenter Growth Reference Study criteria. We measured fat-free mass (FFM) in 1393 (49% female) infants from birth to 6 months of age (Australia, India, and South Africa; n = 468), 3-24 months of age (Brazil, Pakistan, South Africa, and Sri Lanka; n = 925), and derived fat mass (FM), fat mass index (FMI), and fat-free mass index (FFMI). Height-for-age (HAZ), weight-for-age (WAZ), and weight-for-length …

Heat Shock Factor 1 Directly Regulates Transsulfuration Pathway To Promote Prostate Cancer Proliferation And Survival, J Spencer Hauck, David Moon, Xue Jiang, Mu-En Wang, Yue Zhao, Lingfan Xu, Holly Quang, William Butler, Ming Chen, Everardo Macias, Xia Gao, Yiping He, Jiaoti Huang

Faculty, Staff and Students Publications

There are limited therapeutic options for patients with advanced prostate cancer (PCa). We previously found that heat shock factor 1 (HSF1) expression is increased in PCa and is an actionable target. In this manuscript, we identify that HSF1 regulates the conversion of homocysteine to cystathionine in the transsulfuration pathway by altering levels of cystathionine-β-synthase (CBS). We find that HSF1 directly binds the CBS gene and upregulates CBS mRNA levels. Targeting CBS decreases PCa growth and induces tumor cell death while benign prostate cells are largely unaffected. Combined inhibition of HSF1 and CBS results in more pronounced inhibition of PCa cell …

Serine Synthesis Via Reversed Shmt2 Activity Drives Glycine Depletion And Acetaminophen Hepatotoxicity In Masld, Alia Ghrayeb, Alexandra C Finney, Bella Agranovich, Daniel Peled, Sumit Kumar Anand, M Peyton Mckinney, Mahasen Sarji, Dongshan Yang, Natan Weissman, Shani Drucker, Sara Isabel Fernandes, Jonatan Fernández-García, Kyle Mahan, Zaid Abassi, Lin Tan, Philip L Lorenzi, James Traylor, Jifeng Zhang, Ifat Abramovich, Y Eugene Chen, Oren Rom, Inbal Mor, Eyal Gottlieb

Faculty, Staff and Student Publications

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects one-third of the global population. Understanding the metabolic pathways involved can provide insights into disease progression and treatment. Untargeted metabolomics of livers from mice with early-stage steatosis uncovered decreased methylated metabolites, suggesting altered one-carbon metabolism. The levels of glycine, a central component of one-carbon metabolism, were lower in mice with hepatic steatosis, consistent with clinical evidence. Stable-isotope tracing demonstrated that increased serine synthesis from glycine via reverse serine hydroxymethyltransferase (SHMT) is the underlying cause for decreased glycine in steatotic livers. Consequently, limited glycine availability in steatotic livers impaired glutathione synthesis under acetaminophen-induced oxidative …

"Once I Take That One Bite": The Consideration Of Harm Reduction As A Strategy To Support Dietary Change For Patients With Diabetes, Alexzandra Gentsch, Megan Reed, Amy Cunningham, Anna Marie Chang, Stephanie Kahn, Danielle Kovalsky, Amanda Doty, Geoffrey Mills, Judd Hollander, Kristin Rising

College of Population Health Faculty Papers

BACKGROUND: Despite well-established guidelines to treat diabetes, many people with diabetes struggle to manage their disease. For many, this struggle is related to challenges achieving nutrition-related lifestyle changes. We examined how people with diabetes describe barriers to maintaining a healthy diet and considered the benefits of using a harm reduction approach to assist patients to achieve nutrition-related goals.

METHODS: This is a secondary analysis of 89 interviews conducted with adults who had type 1 or type 2 diabetes. Interviews were analyzed using a content analysis approach. Themes regarding food or diet were initially captured in a "food" node. Data in …