Digital Commons Network^™

Economic Equity And People With Disabilities: Development And Characterization Of A Novel Index, Bhavneet Walia, Katherine Mcdonald, Joy Hammel, Lex Frieden, Michael Morris, Barry Whaley, Vinh Nguyen

Faculty, Staff and Student Publications

Here we develop two new social indices: The ADA PARC Absolute Economic Opportunity Index and the ADA PARC Relative Economic Opportunity Index. These indices allow us novel examinations of economic equity between people with and without disabilities within a U.S. State and between people with disabilities in different states using aggregations of multiple component economic indicators. These represent the first efforts to offer U.S. indices of this focus, an important development given the distinct economic needs of people with disabilities and the value in accounting for distinct national policies. The indices rely on U.S. Census and other data on economic …

Exercise Training Reduces The Inflammatory Response And Promotes Intestinal Mucosa-Associated Immunity In Lynch Syndrome, Nan Deng, Laura Reyes-Uribe, Johannes F Fahrmann, Whittney S Thoman, Mark F Munsell, Jennifer B Dennison, Eunice Murage, Ranran Wu, Ernest T Hawk, Selvi Thirumurthi, Patrick M Lynch, Christina M Dieli-Conwright, Alexander J Lazar, Sonali Jindal, Khoi Chu, Manoj Chelvanambi, Karen Basen-Engquist, Yisheng Li, Jennifer A Wargo, Florencia Mcallister, James P Allison, Padmanee Sharma, Krishna M Sinha, Samir Hanash, Susan C Gilchrist, Eduardo Vilar

Faculty, Staff and Student Publications

PURPOSE: Lynch syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacologic intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers.

PATIENTS AND METHODS: To address this, we enrolled 21 patients with LS onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes 3 times weekly for 45 minutes …

Early Skeletal Muscle Loss In Adolescent And Young Adult Cancer Patients Treated With Anthracycline Chemotherapy, Savannah V Wooten, Fei Wang, Michael E Roth, Guanshu Liu, J Andrew Livingston, Behrang Amini, Susan C Gilchrist, Michelle Hildebrandt, Eugenie S Kleinerman

Faculty, Staff and Student Publications

BACKGROUND: Early skeletal muscle loss has been observed in adolescent and young adult (AYA) sarcoma patients undergoing treatment. Identification of individuals within the AYA populace that are at greatest risk of anthracycline-induced skeletal muscle loss is unknown. Moreover, investigations which seek out underlying causes of skeletal muscle degradation during chemotherapy are critical for understanding, preventing, and reducing chronic health conditions associated with poor skeletal muscle status.

METHODS: Computed tomography (CT) scans were used to investigate changes in skeletal muscle of 153 AYA sarcoma and Hodgkin lymphoma patients at thoracic vertebra 4 after anthracycline treatment. Images were examined at three time …

State-Of-The-Art Document On Optimal Contemporary Management Of Cardiomyopathies, Petar M Seferović, Marija Polovina, Giuseppe Rosano, Biykem Bozkurt, Marco Metra, Stephane Heymans, Wilfried Mullens, Johann Bauersachs, Karen Sliwa, Rudolf A De Boer, Dimitrios Farmakis, Thomas Thum, Iacopo Olivotto, Claudio Rapezzi, Aleš Linhart, Domenico Corrado, Carsten Tschöpe, Ivan Milinković, Antoni Bayes Genis, Gerasimos Filippatos, Andre Keren, Milika Ašanin, Gordana Krljanac, Ružica Maksimović, Hadi Skouri, Tuvia Ben Gal, Brenda Moura, Maurizio Volterrani, Magdy Abdelhamid, Yuri Lopatin, Ovidiu Chioncel, Andrew J S Coats

Faculty, Staff and Students Publications

Cardiomyopathies represent significant contributors to cardiovascular morbidity and mortality. Over the past decades, a progress has occurred in characterization of the genetic background and major pathophysiological mechanisms, which has been incorporated into a more nuanced diagnostic approach and risk stratification. Furthermore, medications targeting core disease processes and/or their downstream adverse effects have been introduced for several cardiomyopathies. Combined with standard care and prevention of sudden cardiac death, these novel and emerging targeted therapies offer a possibility of improving the outcomes in several cardiomyopathies. Therefore, the aim of this document is to summarize practical approaches to the treatment of cardiomyopathies, which …

Untargeted Metabolomic Analysis Investigating Links Between Unprocessed Red Meat Intake And Markers Of Inflammation, Alexis C Wood, Goncalo Graca, Meghana Gadgil, Mackenzie K Senn, Matthew A Allison, Ioanna Tzoulaki, Philip Greenland, Timothy Ebbels, Paul Elliott, Mark O Goodarzi, Russell Tracy, Jerome I Rotter, David Herrington

Faculty, Staff and Students Publications

BACKGROUND: Whether red meat consumption is associated with higher inflammation or confounded by increased adiposity remains unclear. Plasma metabolites capture the effects of diet after food is processed, digested, and absorbed, and correlate with markers of inflammation, so they can help clarify diet-health relationships.

OBJECTIVE: To identify whether any metabolites associated with red meat intake are also associated with inflammation.

METHODS: A cross-sectional analysis of observational data from older adults (52.84% women, mean age 63 ± 0.3 y) participating in the Multi-Ethnic Study of Atherosclerosis (MESA). Dietary intake was assessed by food-frequency questionnaire, alongside C-reactive protein (CRP), interleukin-2, interleukin-6, fibrinogen, …

Site-Specific Pathophysiology In A Neonatal Mouse Model Of Gastroparesis, Price T Edwards, Krishnakant G Soni, Margaret E Conner, Stephanie W Fowler, Jaime P P Foong, Rhian Stavely, Lily S Cheng, Geoffrey A Preidis

Faculty, Staff and Students Publications

BACKGROUND: Early-life events impact maturation of the gut microbiome, enteric nervous system, and gastrointestinal motility. We examined three regions of gastric tissue to determine how maternal separation and gut microbes influence the structure and motor function of specific regions of the neonatal mouse stomach.

METHODS: Germ-free and conventionally housed C57BL/6J mouse pups underwent timed maternal separation (TmSep) or nursed uninterrupted (controls) until 14 days of life. We assessed gastric emptying by quantifying the progression of gavaged fluorescein isothiocyanate (FITC)-dextran. With isolated rings of forestomach, corpus, and antrum, we measured tone and contractility by force transduction, gastric wall thickness by light …

Breastfeeding And Risk Of Childhood Brain Tumors: A Report From The Childhood Cancer And Leukemia International Consortium, Jeremy M Schraw, Eleni Th Petridou, Audrey Bonaventure, John D Dockerty, Maria Karalexi, Evangelia Ntzani, Claire Infante-Rivard, Jacqueline Clavel, Paige M Bracci, Roberta Mckean-Cowdin, Eve Roman, Eleanor Kane, Friederike Erdmann, Joachim Schüz, Beth A Mueller, Michael E Scheurer

Faculty, Staff and Students Publications

Purpose: Studies report mixed findings regarding the association of breastfeeding with childhood brain tumors (CBT), the leading causes of cancer-related mortality in young people. Our objective was to determine whether breastfeeding is associated with CBT incidence.

Methods: We pooled data on N = 2610 cases with CBT (including 697 cases with astrocytoma, 447 cases with medulloblastoma/primitive neuroectodermal tumor [PNET], 167 cases with ependymoma) and N = 8128 age- and sex-matched controls in the Childhood Cancer and Leukemia International Consortium. We computed unconditional logistic regression models to estimate the odds ratio (OR) and 95% confidence interval (CI) of CBT, astrocytoma, medulloblastoma/PNET, …

Corrigendum To 'Pressure-Mediated Reflection Spectroscopy Criterion Validity As A Biomarker Of Fruit And Vegetable Intake: A 2-Site Cross-Sectional Study Of 4 Racial Or Ethnic Groups' [J Nutr 2022;152:107-116], Stephanie B Jilcott Pitts, Nancy E Moran, Qiang Wu, Lisa Harnack, Neal E Craft, Neil Hanchard, Ronny Bell, Stacey G Moe, Nevin Johnson, Justice Obasohan, Pamela L Carr-Manthe, Melissa N Laska

Children’s Nutrition Research Center Staff Publications

No abstract provided.

Examining Potential Modifiers Of Human Skin And Plasma Carotenoid Responses In A Randomized Trial Of A Carotenoid-Containing Juice Intervention, Stephanie B Jilcott Pitts, Qiang Wu, Nancy E Moran, Melissa N Laska, Lisa Harnack

Children’s Nutrition Research Center Staff Publications

Background: Skin carotenoid measurements are emerging as a valid and reliable indicator of fruit and vegetable intake and carotenoid intake. However, little is known about the extent to which skin carotenoid responsivity to dietary changes differs based on demographic and physiologic characteristics.

Objectives: This study examined potential effect modifiers of skin carotenoid and plasma carotenoid responses to a carotenoid-rich juice intervention.

Methods: We leveraged data from 2 arms of a 3-site randomized controlled trial of a carotenoid-containing juice intervention (moderate dose = 6 ounces juice, 4 mg total carotenoids/d, high dose = 12 ounces juice, 8 mg total carotenoids/d) (n …

Genome-Wide Interaction Analysis Of Folate For Colorectal Cancer Risk, Emmanouil Bouras, Andre E Kim, Yi Lin, John Morrison, Mengmeng Du, Demetrius Albanes, Elizabeth L Barry, James W Baurley, Sonja I Berndt, Stephanie A Bien, Timothy D Bishop, Hermann Brenner, Arif Budiarto, Andrea Burnett-Hartman, Peter T Campbell, Robert Carreras-Torres, Graham Casey, Tjeng Wawan Cenggoro, Andrew T Chan, Jenny Chang-Claude, David V Conti, Michelle Cotterchio, Matthew Devall, Virginia Diez-Obrero, Niki Dimou, David A Drew, Jane C Figueiredo, Graham G Giles, Stephen B Gruber, Marc J Gunter, Tabitha A Harrison, Akihisa Hidaka, Michael Hoffmeister, Jeroen R Huyghe, Amit D Joshi, Eric S Kawaguchi, Temitope O Keku, Anshul Kundaje, Loic Le Marchand, Juan Pablo Lewinger, Li Li, Brigid M Lynch, Bharuno Mahesworo, Satu Männistö, Victor Moreno, Neil Murphy, Polly A Newcomb, Mireia Obón-Santacana, Jennifer Ose, Julie R Palmer, Nikos Papadimitriou, Bens Pardamean, Andrew J Pellatt, Anita R Peoples, Elizabeth A Platz, John D Potter, Lihong Qi, Conghui Qu, Gad Rennert, Edward Ruiz-Narvaez, Lori C Sakoda, Stephanie L Schmit, Anna Shcherbina, Mariana C Stern, Yu-Ru Su, Catherine M Tangen, Duncan C Thomas, Yu Tian, Caroline Y Um, Franzel Jb Van Duijnhoven, Bethany Van Guelpen, Kala Visvanathan, Jun Wang, Emily White, Alicja Wolk, Michael O Woods, Cornelia M Ulrich, Li Hsu, W James Gauderman, Ulrike Peters, Konstantinos K Tsilidis

Faculty, Staff and Student Publications

Background: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC.

Objectives: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk.

Methods: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) …

Burden Of Respiratory Failure In Pediatric Patients: Analysis Of A Prospective Multicenter Cohort In Bogotá, Colombia, Laura Hernández-Corredor, Rocio Plazas-Pachón, Fernanda Argote-Bolaños, Pedro Barrera-Lopez, Melisa Naranjo Vanegas, Sergio Moreno-Lopez, Paola Rueda-Guevara, Juan G Piñeros, Olga Lucía Baquero Castañeda, Carolina Bonilla, Luz M Mejía, María L Mesa, Sonia Restrepo-Gualteros, Andrea Ramírez Varela

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: The approach to the burden of disease is a demographic, economic, and a health problem, which requires the design and application of specific measures of cost of the disease, such as disability-adjusted life years (DALYs), to establish better public health policies in the pediatric population. The aim of this study is to approach the burden of disease in children with acute respiratory failure (ARF) through the calculation of DALYs.

METHODS: This study was conducted in the framework of a prospective, multicenter cohort in Bogotá, Colombia. Inclusion criteria were all pediatric patients admitted to the emergency department, hospitalization, …

Blood-Based Migration Signature Biomarker Panel Discriminates Early Stage New Onset Diabetes Related Pancreatic Ductal Adenocarcinoma From Type 2 Diabetes, Seetharaman Balasenthil, Suyu Liu, Jianliang Dai, William R Bamlet, Gloria Petersen, Suresh T Chari, Anirban Maitra, Nanyue Chen, Subrata Sen, Ann Mcneill Killary

Faculty, Staff and Student Publications

Background and aims: While type 2 diabetes is a well-known risk factor for pancreatic ductal adenocarcinoma (PDAC), PDAC-induced new-onset diabetes (PDAC-NOD) is a manifestation of underlying PDAC. In this study, we sought to identify potential blood-based biomarkers for distinguishing PDAC-NOD from type 2 diabetes (T2DM) without PDAC.

Materials and methods: By ELISA analysis, a migration signature biomarker panel comprising tissue factor pathway inhibitor (TFPI), tenascin C (TNC-FNIII-C) and CA 19-9 was analyzed in plasma samples from 50 PDAC-NOD and 50 T2DM controls.

Results: Both TFPI (area under the curve (AUC) 0.71) and TNC-FNIII-C (AUC 0.69) outperformed CA 19-9 (AUC 0.60) …

Benefits Of The Enhanced Recovery After Surgery (Eras) Pathway With Quadratus Lumborum Blocks For Minimally Invasive Gynecologic Surgery Patients: A Retrospective Cohort Study, Paul S Lee, Laurie L Brunette, Intira Sriprasert, Mohamed Eloustaz, Rasika Deshpande, Crystal Adams, Laila Muderspach, Lynda Roman, Shane Dickerson, Michael P Kim

Faculty, Staff and Student Publications

STUDY OBJECTIVE: This study aimed to determine the effect of the implementation of the Enhanced Recovery After Surgery (ERAS) protocol among patients receiving minimally invasive gynecologic surgery.

DESIGN AND SETTING: This retrospective cohort study was performed in a tertiary care hospital.

PATIENTS: A total of 328 females who underwent minimally invasive gynecologic surgeries requiring at least one overnight stay at Keck Hospital of University of Southern California (USC), California, USA, from 2016 to 2020 were included in this study.

INTERVENTIONS: The institutional ERAS protocol was implemented in late 2018. A total of 186 patients from 2016 to 2018 prior to …

Elevated Blood Pressure Accelerates White Matter Brain Aging Among Late Middle-Aged Women: A Mendelian Randomization Study In The Uk Biobank, Li Feng, Zhenyao Ye, Chen Mo, Jingtao Wang, Song Liu, Si Gao, Hongjie Ke, Travis A Canida, Yezhi Pan, Marleen M J Van Greevenbroek, Alfons J H M Houben, Kai Wang, Kathryn S Hatch, Yizhou Ma, David K Y Lei, Chixiang Chen, Braxton D Mitchell, L Elliot Hong, Peter Kochunov, Shuo Chen, Tianzhou Ma

Faculty, Staff and Student Publications

BACKGROUND: Elevated blood pressure (BP) is a modifiable risk factor associated with cognitive impairment and cerebrovascular diseases. However, the causal effect of BP on white matter brain aging remains unclear.

METHODS: In this study, we focused on N  = 228 473 individuals of European ancestry who had genotype data and clinical BP measurements available (103 929 men and 124 544 women, mean age = 56.49, including 16 901 participants with neuroimaging data available) collected from UK Biobank (UKB). We first established a machine learning model to compute the outcome variable brain age gap (BAG) based on white matter microstructure integrity …

Pancreatic Replacement Therapy For Maladaptive Behaviors In Preschool Children With Autism Spectrum Disorder, Deborah A Pearson, Robert L Hendren, Matthew F Heil, William R Mcintyre, Shane R Raines

Faculty, Staff and Student Publications

IMPORTANCE: There is an urgent unmet need for a treatment addressing the core symptoms and associated maladaptive symptoms of autism spectrum disorder (ASD), especially in preschool populations.

OBJECTIVES: To evaluate whether treatment of children with ASD aged 3 to 6 years treated with high-protease pancreatic therapy produces long- and short-term improvements in autism-associated maladaptive behaviors.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study at 32 sites across the US used a double-blind parallel group, delayed-start design comprising a 2-week blinded placebo run-in, and a double-blind, randomized, placebo-controlled segment (12 weeks). Children were recruited into the study in 2015, with data collection …

Aortic Arch Reconstruction Using Nonvalved Femoral Vein Homograft In High-Risk Neonates, Kyle G Mitchell, Julija Dobrila, Blaz Podgorsek, Christopher Greenleaf, Peter Chen, Jorge D Salazar, Damien J Lapar

Faculty, Staff and Student Publications

Aortic arch obstruction is often present with complex concomitant congenital heart defects (CHDs). The use of nonvalved femoral vein homograft (FVH) to reconstruct the aortic arch has distinct surgical advantages, including simplified reconstruction. We present an intraoperative video of a Yasui procedure utilizing FVH for aortic reconstruction in a 12-day-old (2.2 kg) neonate with right ventricular outflow tract obstruction, malalignment ventricular septal defect, aortic valve atresia, aortic arch hypoplasia, atrial septal defect, and ductal dependent systemic circulation. Further, we report outcomes for a series of three additional neonatal patients with complex CHD and aortic arch obstruction who underwent FVH arch …

Effectiveness Of Icosapent Ethyl On First And Total Cardiovascular Events In Patients With Metabolic Syndrome, But Without Diabetes: Reduce-It Metsyn, Michael Miller, Deepak L Bhatt, Eliot A Brinton, Terry A Jacobson, Philippe Gabriel Steg, Armando Lira Pineda, Steven B Ketchum, Ralph T Doyle, Jean-Claude Tardif, Christie M Ballantyne

Faculty, Staff and Students Publications

Aims: Metabolic syndrome (MetSyn) is associated with high risk of cardiovascular (CV) events, irrespective of statin therapy. In the overall REDUCE-IT study of statin-treated patients, icosapent ethyl (IPE) reduced the risk of the primary composite endpoint (CV death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, or unstable angina requiring hospitalization) and the key secondary composite endpoint (CV death, non-fatal myocardial infarction, or non-fatal stroke).

Methods and results: REDUCE-IT was an international, double-blind trial that randomized 8179 high CV risk statin-treated patients with controlled LDL cholesterol and elevated triglycerides, to IPE 4 g/day or placebo. The current study evaluated the pre-specified …

Relationships Among Intragastric Meal Distribution During Gastric Emptying Scintigraphy, Water Consumption During Water Load Satiety Testing, And Symptoms Of Gastroparesis, Henry P Parkman, Laura A Wilson, Paul Silver, Alan H Maurer, Irene Sarosiek, Robert S Bulat, Braden Kuo, Madhusudan Grover, Gianrico Farrugia, Bruno P Chumpitazi, Robert J Shulman, Zubair Malik, Laura A Miriel, James Tonascia, Frank Hamilton, Thomas L Abell, Pankaj J Pasricha, Richard W Mccallum, Kenneth L Koch, Niddk Gastroparesis Clinical Research Consortium

Faculty, Staff and Students Publications

Gastric emptying scintigraphy (GES) measures total gastric retention after a solid meal and can assess intragastric meal distribution (IMD). Water load satiety test (WLST) measures gastric capacity. Both IMD immediately after meal ingestion [ratio of proximal gastric counts after meal ingestion to total gastric counts at time 0 (IMD⁰)] and WLST (volume of water ingested over 5 min) are indirect measures of gastric accommodation. In this study, IMD⁰ and WLST were compared with each other and to symptoms of gastroparesis to gauge their clinical utility for assessing patients with symptoms of gastroparesis. Patients with symptoms of gastroparesis …

P2y2 Purinergic Receptor Gene Deletion Protects Mice From Bacterial Endotoxin And Sepsis-Associated Liver Injury And Mortality, Athis R Arunachalam, Sanju S Samuel, Arunmani Mani, Janielle P Maynard, Kelsey M Stayer, Eric Dybbro, Subapradha Narayanan, Aalekhya Biswas, Saliha Pathan, Krishnakant Soni, Abu Hena Mostafa Kamal, Chandra Shekar R Ambati, Nagireddy Putluri, Moreshwar S Desai, Sundararajah Thevananther

Faculty, Staff and Students Publications

The liver plays a significant role in regulating a wide range of metabolic, homeostatic, and host-defense functions. However, the impact of liver injury on the host's ability to control bacteremia and morbidity in sepsis is not well understood. Leukocyte recruitment and activation lead to cytokine and chemokine release, which, in turn, trigger hepatocellular injury and elevate nucleotide levels in the extracellular milieu. P2Y2 purinergic receptors, G protein-coupled and activated by extracellular ATP/UTP, are expressed at the cell surface of hepatocytes and nonparenchymal cells. We sought to determine whether P2Y2 purinergic receptor function is necessary for the maladaptive host response to …

Ascertainment Of Minimal Clinically Important Differences In The Diabetes Distress Scale-17: A Secondary Analysis Of A Randomized Clinical Trial, Jack Banks, Amber B Amspoker, Elizabeth M Vaughan, Lechauncy Woodard, Aanand D Naik

Faculty, Staff and Student Publications

IMPORTANCE: The Diabetes Distress Scale-17 (DDS-17) is a common measure of diabetes distress. Despite its popularity, there are no agreed-on minimal clinically important difference (MCID) values for the DDS-17.

OBJECTIVE: to establish a distribution-based metric for MCID in the DDS-17 and its 4 subscale scores (interpersonal distress, physician distress, regimen distress, and emotional distress).

DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of a randomized clinical trial used baseline and postintervention data from a hybrid (implementation-effectiveness) trial evaluating Empowering Patients in Chronic Care (EPICC) vs an enhanced form of usual care (EUC). Participants included adults with uncontrolled type 2 diabetes (glycated …

Dicarboxylic Acylcarnitine Biomarkers In Peroxisome Biogenesis Disorders, Michael F Wangler, Barbara Lesko, Rejwi Dahal, Sharayu Jangam, Pradnya Bhadane, Theodore E Wilson, Molly Mcpheron, Marcus J Miller

Duncan NRI Faculty and Staff Publications

The peroxisome is an essential eukaryotic organelle with diverse metabolic functions. Inherited peroxisomal disorders are associated with a wide spectrum of clinical outcomes and are broadly divided into two classes, those impacting peroxisome biogenesis (PBD) and those impacting specific peroxisomal factors. Prior studies have indicated a role for acylcarnitine testing in the diagnosis of some peroxisomal diseases through the detection of long chain dicarboxylic acylcarnitine abnormalities (C16-DC and C18-DC). However, there remains limited independent corroboration of these initial findings and acylcarnitine testing for peroxisomal diseases has not been widely adopted in clinical laboratories. To explore the utility of acylcarnitine testing …

Human Intestinal Organoids From Cronkhite-Canada Syndrome Patients Reveal Link Between Serotonin And Proliferation, Victoria Poplaski, Carolyn Bomidi, Amal Kambal, Hoa Nguyen-Phuc, Sara C Di Rienzi, Heather A Danhof, Xi-Lei Zeng, Linda A Feagins, Nan Deng, Eduardo Vilar, Florencia Mcallister, Cristian Coarfa, Soyoun Min, Hyun Jung Kim, Richa Shukla, Robert Britton, Mary K Estes, Sarah E Blutt

Faculty, Staff and Student Publications

Cronkhite-Canada Syndrome (CCS) is a rare, noninherited polyposis syndrome affecting 1 in every million individuals. Despite over 50 years of CCS cases, the etiopathogenesis and optimal treatment for CCS remains unknown due to the rarity of the disease and lack of model systems. To better understand the etiology of CCS, we generated human intestinal organoids (HIOs) from intestinal stem cells isolated from 2 patients. We discovered that CCS HIOs are highly proliferative and have increased numbers of enteroendocrine cells producing serotonin (also known as 5-hydroxytryptamine or 5HT). These features were also confirmed in patient tissue biopsies. Recombinant 5HT increased proliferation …

P2y2 Purinergic Receptor Gene Deletion Protects Mice From Bacterial Endotoxin And Sepsis-Associated Liver Injury And Mortality, Athis R Arunachalam, Sanju S Samuel, Arunmani Mani, Janielle P Maynard, Kelsey M Stayer, Eric Dybbro, Subapradha Narayanan, Aalekhya Biswas, Saliha Pathan, Krishnakant Soni, Abu Hena Mostafa Kamal, Chandra Shekar R Ambati, Nagireddy Putluri, Moreshwar S Desai, Sundararajah Thevananther

Faculty, Staff and Students Publications

Prostate cancer (PCa) remains a leading cause of mortality among American men, with metastatic and recurrent disease posing significant therapeutic challenges due to a limited comprehension of the underlying biological processes governing disease initiation, dormancy, and progression. The conventional use of PCa cell lines has proven inadequate in elucidating the intricate molecular mechanisms driving PCa carcinogenesis, hindering the development of effective treatments. To address this gap, patient-derived primary cell cultures have been developed and play a pivotal role in unraveling the pathophysiological intricacies unique to PCa in each individual, offering valuable insights for translational research. This review explores the applications …

Therapeutic Implications Of Impaired Nuclear Receptor Function And Dysregulated Metabolism In Wilson’S Disease, Clavia Ruth Wooton-Kee

Faculty, Staff and Students Publications

Copper is an essential trace element that is required for the activity of many enzymes and cellular processes, including energy homeostasis and neurotransmitter biosynthesis; however, excess copper accumulation results in significant cellular toxicity. The liver is the major organ for maintaining copper homeostasis. Inactivating mutations of the copper-transporting P-type ATPase, ATP7B, result in Wilson’s disease, an autosomal recessive disorder that requires life-long medicinal therapy or liver transplantation. Current treatment protocols are limited to either sequestration of copper via chelation or reduction of copper absorption in the gut (zinc therapy). The goal of these strategies is to reduce free copper, redox …

Bone Health In Children With Recurrent And Chronic Pancreatitis: A Multi-Center Cross Sectional Analysis, Maisam Abu-El-Haija, Lindsey Hornung, Kate Ellery, Douglas S Fishman, Tanja Y Gonska, Cheryl Gariepy, Mark Lowe, Katie Larson Ode, Asim Maqbool, Maria Mascarenhas, Veronique D Morinville, Chee Y Ooi, Emily R Perito, Sarah Jane Schwarzenberg, Zachary M Sellers, Babette S Zemel, Ying Yuan, Fuchenchu Wang, Aliye Uc, Heidi J Kalkwarf

Faculty, Staff and Students Publications

BACKGROUND/OBJECTIVES: Bone health of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) is not well studied.

METHODS: This retrospective study was performed at three sites and included data from INSPPIRE-2.

RESULTS: Of the 87 children in the study: 46 had ARP (53%), 41 had CP (47%). Mean age was 13.6 ± 3.9 years at last DXA scan. The prevalence of low height-for-age (Z-score < -2) (13%, 10/78) and low bone mineral density (BMD) adjusted for height (Z-score < -2) (6.4%, 5/78) were higher than a healthy reference sample (2.5%, p < 0.0001 and p = 0.03, respectively).

CONCLUSION: Children with ARP or CP have lower height and BMD than healthy peers. Attention to deficits in growth and bone mineral accrual in children with pancreatic disease is warranted.

Preterm Pigs Fed Donor Human Milk Have Greater Liver Β-Carotene Concentrations Than Pigs Fed Infant Formula, Nancy E Moran, Joshua Wade, Rachel Stroh, Barbara Stoll, Gregory Guthrie, Amy B Hair, Douglas G Burrin

Faculty, Staff and Students Publications

BACKGROUND: Milk carotenoids may support preterm infant health and neurodevelopment. Infants fed human milk often have higher blood and tissue carotenoid concentrations than infants fed carotenoid-containing infant formula (IF). Donor human milk (DHM) is a supplement to mother's own milk, used to support preterm infant nutrition.

OBJECTIVES: We tested whether tissue and plasma β-carotene concentrations would be higher in preterm pigs fed pasteurized DHM versus premature IF.

METHODS: This is a secondary analysis of samples collected from a study of the effects of enteral diet composition on necrotizing enterocolitis incidence. Preterm pigs received partial enteral feeding of either DHM (n …

Aso Silencing Of A Glycosyltransferase, Poglut1, Improves The Liver Phenotypes In Mouse Models Of Alagille Syndrome, Nima Niknejad, Duncan Fox, Jennifer L Burwinkel, Neda Zarrin-Khameh, Soomin Cho, Armand Soriano, Ashley E Cast, Mario F Lopez, Kari A Huppert, Frank Rigo, Stacey S Huppert, Paymaan Jafar-Nejad, Hamed Jafar-Nejad

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Paucity of intrahepatic bile ducts (BDs) is caused by various etiologies and often leads to cholestatic liver disease. For example, in patients with Alagille syndrome (ALGS), which is a genetic disease primarily caused by mutations in jagged 1 ( JAG1) , BD paucity often results in severe cholestasis and liver damage. However, no mechanism-based therapy exists to restore the biliary system in ALGS or other diseases associated with BD paucity. Based on previous genetic observations, we investigated whether postnatal knockdown of the glycosyltransferase gene protein O -glucosyltransferase 1 ( Poglut1) can improve the ALGS liver phenotypes in …

Delays In Hepatitis B Immunization Series Completion In People With Human Immunodeficiency Virus, Daanish Sheikh, Kristen A Staggers, Jennifer Carey, Wendy A Keitel, Robert L Atmar, Hana M El Sahly, Jennifer A Whitaker

Faculty, Staff and Students Publications

BACKGROUND: Studies have demonstrated low hepatitis B virus (HBV) vaccine series completion among persons with human immunodeficiency virus (HIV).

METHODS: We conducted a retrospective record review of persons entering HIV care at 2 clinics in Houston, Texas, between 2010 and 2018. Kaplan-Meier curves summarized time to receipt of HBV vaccines for those eligible for vaccination. We estimated the proportions of patients who had received 1, 2, or 3 HBV vaccine doses at 12 and 24 months after entry to care. A Prentice Williams and Peterson total time model was used to evaluate associations between patient characteristics and time to vaccination. …

Baseline Leptin Predicts Response To Metformin In Adolescents With Type 1 Diabetes And Increased Body Mass Index, Heba M Ismail, Souptik Barua, Johnny Wang, Ashutosh Sabharwal, Ingrid Libman, Fida Bacha, Kristen J Nadeau, Mustafa Tosur, Maria J Redondo

Faculty, Staff and Students Publications

No abstract provided.

Obesity Dominates Early Effects On Cardiac Structure And Arterial Stiffness In People With Type 2 Diabetes, Layla A Abushamat, Daniel Enge, Takashi Fujiwara, Michal Schäfer, Ethan W Clark, Erin K Englund, Rebecca L Scalzo, Aspen Johnston, Deirdre Rafferty, Irene E Schauer, Mary O Whipple, Kendall Hunter, Amy G Huebschmann, Kristen J Nadeau, Kelly Jarvis, Alex J Barker, Judith G Regensteiner, Jane E B Reusch

Faculty, Staff and Students Publications

OBJECTIVE: Type 2 diabetes (T2D) and obesity are global epidemics leading to excess cardiovascular disease (CVD). This study investigates standard and novel cardiac MRI parameters to detect subclinical cardiac and central vascular dysfunction in inactive people with and without T2D.

METHODS: Physically inactive age and BMI-similar premenopausal women and men with ( n  = 22) and without [ n  = 34, controls with overweight/obesity (CWO)] uncomplicated T2D were compared to an age-similar and sex-similar reference control cohort ( n  = 20). Left ventricular (LV) structure, function, and aortic stiffness were assessed by MRI. Global arterial pulse wave velocity (PWV) was …