Digital Commons Network^™

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

Faculty, Staff and Students Publications

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

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

The Roles Of Cyp1a2 And Cyp2d In Pharmacokinetic Profiles Of Serotonin And Norepinephrine Reuptake Inhibitor Duloxetine And Its Metabolites In Mice, Xuan Qin, Cen Xie, John M Hakenjos, Kevin R Mackenzie, Shelton R Boyd, Mercedes Barzi, Karl-Dimiter Bissig, Damian W Young, Feng Li

Faculty, Staff and Students Publications

Duloxetine (DLX) is widely used to treat major depressive disorder. Little is known about the mechanistic basis for DLX-related adverse effects (e.g., liver injury). Human CYP1A2 and CYP2D6 mainly contributes to DLX metabolism, which was proposed to be involved in its adverse effects. Here, we investigated the roles of Cyp1a2 and Cyp2d on DLX pharmacokinetic profile and tissue distribution using a Cyp1a2 knockout (Cyp1a2-KO) mouse model together with a Cyp2d inhibitor (propranolol). Cyp1a2-KO has the few effects on the systematic exposure (area under the plasma concentration-time curve, AUC) and tissue disposition of DLX and its primary metabolites. Propranolol dramatically increased …

Maternal Western Diet Is Associated With Distinct Preclinical Pediatric Nafld Phenotypes In Juvenile Nonhuman Primate Offspring, Michael J Nash, Evgenia Dobrinskikh, Rachel C Janssen, Mark A Lovell, Deborah A Schady, Claire Levek, Kenneth L Jones, Angelo D'Alessandro, Paul Kievit, Kjersti M Aagaard, Carrie E Mccurdy, Maureen Gannon, Jacob E Friedman, Stephanie R Wesolowski

Faculty, Staff and Students Publications

Pediatric NAFLD has distinct and variable pathology, yet causation remains unclear. We have shown that maternal Western-style diet (mWSD) compared with maternal chow diet (CD) consumption in nonhuman primates produces hepatic injury and steatosis in fetal offspring. Here, we define the role of mWSD and postweaning Western-style diet (pwWSD) exposures on molecular mechanisms linked to NAFLD development in a cohort of 3-year-old juvenile nonhuman primates offspring exposed to maternal CD or mWSD followed by CD or Western-style diet after weaning. We used histologic, transcriptomic, and metabolomic analyses to identify hepatic pathways regulating NAFLD. Offspring exposed to mWSD showed increased hepatic …

Effect Of Liquid And Solid Test Meals On Symptoms And Gastric Myoelectrical Activity In Patients With Gastroparesis And Functional Dyspepsia, Kenneth L Koch, Mark Van Natta, Henry P Parkman, Madhusudan Grover, Thomas L Abell, Richard W Mccallum, Hossam A Shaltout, Irene Sarosiek, Gianrico Farrugia, Robert J Shulman, James Tonascia, Laura Miriel, Frank Hamilton, Pankaj J Pasricha, Gastroparesis Clinical Research Consortium

Faculty, Staff and Students Publications

BACKGROUND: Patients with gastroparesis (GP) and functional dyspepsia (FD) have similar symptoms, but the pathophysiology of postprandial symptoms remains uncertain.

AIMS: To compare symptoms and gastric myoelectrical activity (GMA) after liquid and solid test meals in patients with GP and FD.

METHODS: Patients enrolled in the Gastroparesis Clinical Research Consortium Registry were studied. Clinical characteristics were measured with standard questionnaires. GP was determined by 4-h solid-phase gastric scintigraphy. GMA was measured using electrogastrography before and after ingestion of a water load or nutrient bar on separate days. Symptoms were measured on visual analog scales. GMA responses to the water load …

Regulation Of Skeletal Muscle Protein Synthesis In The Preterm Pig By Intermittent Leucine Pulses During Continuous Parenteral Feeding, Marko Rudar, Agus Suryawan, Hanh V Nguyen, Shaji K Chacko, Caitlin Vonderohe, Barbara Stoll, Douglas G Burrin, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

BACKGROUND: Extrauterine growth restriction is a common complication of preterm birth. Leucine (Leu) is an agonist for the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signaling pathway that regulates translation initiation and protein synthesis in skeletal muscle. Previously, we showed that intermittent intravenous pulses of Leu to neonatal pigs born at term receiving continuous enteral nutrition increases muscle protein synthesis and lean mass accretion. Our objective was to determine the impact of intermittent intravenous pulses of Leu on muscle protein anabolism in preterm neonatal pigs administered continuous parenteral nutrition.

METHODS: Following preterm delivery (on day 105 of 115 gestation), …

Serum Biomarkers Correlated With Liver Stiffness Assessed In A Multicenter Study Of Pediatric Cholestatic Liver Disease, Daniel H Leung, Sridevi Devaraj, Nathan P Goodrich, Xinpu Chen, Deepthi Rajapakshe, Wen Ye, Victor Andreev, Charles G Minard, Danielle Guffey, Jean P Molleston, Lee M Bass, Saul J Karpen, Binita M Kamath, Kasper S Wang, Shikha S Sundaram, Philip Rosenthal, Patrick Mckiernan, Kathleen M Loomes, M Kyle Jensen, Simon P Horslen, Jorge A Bezerra, John C Magee, Robert M Merion, Ronald J Sokol, Benjamin L Shneider, Estella Alonso, Lee Bass, Susan Kelly, Mary Riordan, Hector Melin-Aldana, Jorge Bezerra, Kevin Bove, James Heubi, Alexander Miethke, Greg Tiao, Julie Denlinger, Erin Chapman, Ronald Sokol, Amy Feldman, Cara Mack, Michael Narkewicz, Frederick Suchy, Shikha S Sundaram, Johan Van Hove, Benigno Garcia, Mikaela Kauma, Kendra Kocher, Matthew Steinbeiss, Mark Lovell, Kathleen M Loomes, David Piccoli, Elizabeth Rand, Pierre Russo, Nancy Spinner, Jessi Erlichman, Samantha Stalford, Dina Pakstis, Sakya King, Robert Squires, Rakesh Sindhi, Veena Venkat, Kathy Bukauskas, Patrick Mckiernan, Lori Haberstroh, James Squires, Philip Rosenthal, Laura Bull, Joanna Curry, Camille Langlois, Grace Kim, Jeffery Teckman, Vikki Kociela, Rosemary Nagy, Shraddha Patel, Jacqueline Cerkoski, Jean P Molleston, Molly Bozic, Girish Subbarao, Ann Klipsch, Cindy Sawyers, Oscar Cummings, Simon P Horslen, Karen Murray, Evelyn Hsu, Kara Cooper, Melissa Young, Laura Finn, Binita M Kamath, Vicky Ng, Claudia Quammie, Juan Putra, Deepika Sharma, Aishwarya Parmar, Stephen Guthery, Kyle Jensen, Ann Rutherford, Amy Lowichik, Linda Book, Rebecka Meyers, Tyler Hall, Kasper S Wang, Sonia Michail, Danny Thomas, Catherine Goodhue, Rohit Kohli, Larry Wang, Nisreen Soufi, Daniel Thomas, Saul Karpen, Nitika Gupta, Rene Romero, Miriam B Vos, Rita Tory, John-Paul Berauer, Carlos Abramowsky, Jeanette Mcfall, Benjamin L Shneider, Sanjiv Harpavat, Paula Hertel, Daniel Leung, Mary Tessier, Deborah Schady, Laurel Cavallo, Diego Olvera, Christina Banks, Cynthia Tsai, Richard Thompson, Edward Doo, Jay Hoofnagle, Averell Sherker, Rebecca Torrance, Sherry Hall, John Magee, Robert Merion, Cathie Spino, Wen Ye

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis.

APPROACH AND RESULTS: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM …

Aortic Stress Activates An Adaptive Program In Thoracic Aortic Smooth Muscle Cells That Maintains Aortic Strength And Protects Against Aneurysm And Dissection In Mice, Chen Zhang, Yanming Li, Abhijit Chakraborty, Yang Li, Kimberly R Rebello, Pingping Ren, Wei Luo, Lin Zhang, Hong S Lu, Lisa A Cassis, Joseph S Coselli, Alan Daugherty, Scott A Lemaire, Ying H Shen

Faculty, Staff and Students Publications

BACKGROUND:

When aortic cells are under stress, such as increased hemodynamic pressure, they adapt to the environment by modifying their functions, allowing the aorta to maintain its strength. To understand the regulation of this adaptive response, we examined transcriptomic and epigenomic programs in aortic smooth muscle cells (SMCs) during the adaptive response to angiotensin II (AngII) infusion and determined its importance in protecting against aortic aneurysm and dissection (AAD).

METHODS:

We performed single-cell RNA sequencing (scRNA-seq) and single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) analyses in a mouse model of sporadic AAD induced by AngII infusion. We also examined the …

A Single-Center Study Of Long-Term Effectiveness Of Vedolizumab In Anti-Tnf Refractory Pediatric Inflammatory Bowel Disease, Halee Patel, Lina Karam, Richard Kellermayer

Faculty, Staff and Students Publications

OBJECTIVES: Vedolizumab is an anti-α4β7 integrin antibody that has been used successfully in the treatment of adult-onset inflammatory bowel diseases (IBDs: Crohn disease [CD] and ulcerative colitis [UC]). Its off-label use in the pediatric IBD (PIBD) population is increasing, but knowledge on durability beyond 6 months of treatment is limited.

METHODS: A real-life, single-center, retrospective study of PIBD patients treated with vedolizumab was performed. Data on demographics, prior and concomitant treatments, and disease activity were obtained at 14 weeks, 26 weeks, 1 year, and 2 years of therapy. Primary outcome was corticosteroid- and other biologic-free remission (based on pediatric ulcerative …

Beyond Varices: Complications Of Cirrhotic Portal Hypertension In Pediatrics, Anna M Banc-Husu, Henry Shiau, Peace Dike, Benjamin L Shneider

Faculty, Staff and Students Publications

Complications of cirrhotic portal hypertension (PHTN) in children are broad and include clinical manifestations ranging from variceal hemorrhage, hepatic encephalopathy (HE), ascites, spontaneous bacterial peritonitis (SBP), and hepatorenal syndrome (HRS) to less common conditions such as hepatopulmonary syndrome, portopulmonary hypertension, and cirrhotic cardiomyopathy. The approaches to the diagnosis and management of these complications have become standard of practice in adults with cirrhosis with many guidance statements available. However, there is limited literature on the diagnosis and management of these complications of PHTN in children with much of the current guidance available focused on variceal hemorrhage. The aim of this review …

Expert Consensus Statement: Management Of Pediatric Persistent Obstructive Sleep Apnea After Adenotonsillectomy, Stacey L Ishman, Stephen Maturo, Seth Schwartz, Margo Mckenna, Cristina M Baldassari, Mathieu Bergeron, Boris Chernobilsky, Zarmina Ehsan, Lisa Gagnon, Yi-Chun Carol Liu, David F Smith, Jeffrey Stanley, Habib Zalzal, Nui Dhepyasuwan

Faculty, Staff and Students Publications

OBJECTIVE: To develop an expert consensus statement regarding persistent pediatric obstructive sleep apnea (OSA) focused on quality improvement and clarification of controversies. Persistent OSA was defined as OSA after adenotonsillectomy or OSA after tonsillectomy when adenoids are not enlarged.

METHODS: An expert panel of clinicians, nominated by stakeholder organizations, used the published consensus statement methodology from the American Academy of Otolaryngology-Head and Neck Surgery to develop statements for a target population of children aged 2-18 years. A medical librarian systematically searched the literature used as a basis for the clinical statements. A modified Delphi method was used to distill expert …

Comparison Of Percentile Tables And Algorithm-Based Calculators For Classification Of Blood Pressures In Children And Adolescents With Obesity: A Secondary Analysis Of A Clinical Trial, William J Pitts, Tami L Cave, Alana Cavadino, Roman J Shypailo, Sarah E Maessen, Paul L Hofman, William Wong, Yvonne C Anderson

Faculty, Staff and Students Publications

AIM: Obesity as a major risk factor for childhood hypertension necessitates careful blood pressure (BP) monitoring of those affected. This study aimed to compare BP classification in a cohort of children affected by obesity using tables versus digital calculations in two sets of guidelines.

METHODS: This study was a secondary analysis of data collected from a randomised clinical trial of a multidisciplinary life-style assessment and intervention program. Baseline data from 237 children with a body mass index >99th percentile or >91st percentile with weight-related comorbidities and available BP measurements were analysed. We assessed agreement between tables and algorithms in classification …

Characterizing Mechanism-Based Pain Phenotypes In Patients With Chronic Pancreatitis: A Cross-Sectional Analysis Of The Prospective Evaluation Of Chronic Pancreatitis For Epidemiologic And Translational Studies, Jami L Saloman, Darwin L Conwell, Evan Fogel, Santhi Swaroop Vege, Liang Li, Shuang Li, Dana K Andersen, William E Fisher, Christopher E Forsmark, Phil A Hart, Stephen J Pandol, Walter G Park, Anna Evans Phillips, Mark Topazian, Stephen K Van Den Eeden, Jose Serrano, Dhiraj Yadav, Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer

Faculty, Staff and Students Publications

Pain is common in chronic pancreatitis (CP) and profoundly reduces quality of life (QoL). Multiple underlying mechanisms contribute to a heterogenous pain experience and reduce efficacy of pain management. This study was designed to characterize the distribution of mechanism-based pain phenotypes in painful CP. The data analyzed were collected as part of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, an NCI/NIDDK-funded longitudinal study of the natural history of CP. The PROspective Evaluation of Chronic pancreatitis for EpidEmiologic and translational stuDies includes patient-reported outcome (PRO) measures of pain, medication use, global health, and QoL. Of subjects (N …

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

Faculty, Staff and Students Publications

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

METHODS: Twenty-four …

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

Faculty, Staff and Students Publications

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

METHODS: Twenty-four …

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

Faculty, Staff and Students Publications

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

METHODS: Twenty-four …

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

Faculty, Staff and Students Publications

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

METHODS: Twenty-four …

Approach To The Patient: Pharmacological Therapies For Fracture Risk Reduction In Adults With Osteogenesis Imperfecta, Winnie Liu, Brendan Lee, Sandesh C S Nagamani, Lindsey Nicol, Frank Rauch, Eric T Rush, V Reid Sutton, Eric Orwoll

Faculty, Staff and Students Publications

Context

Osteogenesis imperfecta (OI) is a genetic disorder characterized by increased bone fragility largely caused by defects in structure, synthesis, or post-translational processing of type I collagen. The effectiveness of medications used for fracture reduction in adults with OI is understudied and practice recommendations are not well established. Drugs currently used to improve skeletal health in OI were initially developed to treat osteoporosis. Oral and intravenous bisphosphonates have been shown to improve bone mineral density (BMD) in adults with OI and are commonly used; however, conclusive data confirming fracture protection are lacking. Similarly, teriparatide appears to increase BMD, an effect …

Brain Nuclear Receptors And Cardiovascular Function, Mengjie Wang, Yongjie Yang, Yong Xu

Faculty, Staff and Students Publications

Brain-heart interaction has raised up increasing attentions. Nuclear receptors (NRs) are abundantly expressed in the brain, and emerging evidence indicates that a number of these brain NRs regulate multiple aspects of cardiovascular diseases (CVDs), including hypertension, heart failure, atherosclerosis, etc. In this review, we will elaborate recent findings that have established the physiological relevance of brain NRs in the context of cardiovascular function. In addition, we will discuss the currently available evidence regarding the distinct neuronal populations that respond to brain NRs in the cardiovascular control. These findings suggest connections between cardiac control and brain dynamics through NR signaling, which …

Association Of Omega 3 Polyunsaturated Fatty Acids With Incident Chronic Kidney Disease: Pooled Analysis Of 19 Cohorts, Kwok Leung Ong, Matti Marklund, Liping Huang, Kerry-Anne Rye, Nicholas Hui, Xiong-Fei Pan, Casey M Rebholz, Hyunju Kim, Lyn M Steffen, Anniek C Van Westing, Johanna M Geleijnse, Ellen K Hoogeveen, Yun-Yu Chen, Kuo-Liong Chien, Amanda M Fretts, Rozenn N Lemaitre, Fumiaki Imamura, Nita G Forouhi, Nicholas J Wareham, Anna Birukov, Susanne Jäger, Olga Kuxhaus, Matthias B Schulze, Vanessa Derenji De Mello, Jaakko Tuomilehto, Matti Uusitupa, Jaana Lindström, Nathan Tintle, William S Harris, Keisuke Yamasaki, Yoichiro Hirakawa, Toshiharu Ninomiya, Toshiko Tanaka, Luigi Ferrucci, Stefania Bandinelli, Jyrki K Virtanen, Ari Voutilainen, Tharusha Jayasena, Anbupalam Thalamuthu, Anne Poljak, Sonia Bustamante, Perminder S Sachdev, Mackenzie K Senn, Stephen S Rich, Michael Y Tsai, Alexis C Wood, Markku Laakso, Maria Lankinen, Xiaowei Yang, Liang Sun, Huaixing Li, Xu Lin, Christoph Nowak, Johan Ärnlöv, Ulf Risérus, Lars Lind, Mélanie Le Goff, Cécilia Samieri, Catherine Helmer, Frank Qian, Renata Micha, Adrienne Tin, Anna Köttgen, Ian H De Boer, David S Siscovick, Dariush Mozaffarian, Jason Hy Wu

Faculty, Staff and Students Publications

OBJECTIVE: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD).

DESIGN: Pooled analysis.

DATA SOURCES: A consortium of 19 studies from 12 countries identified up to May 2020.

STUDY SELECTION: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate.

DATA EXTRACTION AND SYNTHESIS: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were …

A Bioengineered Probiotic For The Oral Delivery Of A Peptide Kv13 Channel Blocker To Treat Rheumatoid Arthritis, Yuqing Wang, Duolong Zhu, Laura C Ortiz-Velez, Jacob L Perry, Michael W Pennington, Joseph M Hyser, Robert A Britton, Christine Beeton

Faculty, Staff and Students Publications

New therapeutics that combine efficacy with limited side effects and can be delivered noninvasively are needed to adequately treat patients with rheumatoid arthritis (RA) and other autoimmune diseases. Kv1.3 channel-expressing CCR7− effector memory T (TEM) lymphocytes are significant players in the pathogenesis of multiple autoimmune diseases, and blocking Kv1.3 reduces disease severity in rat models of RA and patients with plaque psoriasis. However, peptide therapeutics require repeated injections, reducing patient compliance. We used a bioengineered Lactobacillus reuteri as an oral delivery method of a Kv1.3 blocker for immunomodulation in rat models of atopic dermatitis and RA. This study demonstrates a …

Differential Co-Expression Networks Of The Gut Microbiota Are Associated With Depression And Anxiety Treatment Resistance Among Psychiatric Inpatients, Dominique S Thompson, Chenlian Fu, Tanmay Gandhi, J Christopher Fowler, B Christopher Frueh, Benjamin L Weinstein, Joseph Petrosino, Julia K Hadden, Marianne Carlson, Cristian Coarfa, Alok Madan

Faculty, Staff and Students Publications

BACKGROUND: Comorbid anxiety and depression are common and are associated with greater disease burden than either alone. Our recent efforts have identified an association between gut microbiota dysfunction and severity of anxiety and depression. In this follow-up, we applied Differential Co-Expression Analysis (DiffCoEx) to identify potential gut microbiota biomarker(s) candidates of treatment resistance among psychiatric inpatients.

METHODS: In a sample of convenience, 100 psychiatric inpatients provided clinical data at admission and discharge; fecal samples were collected early during the hospitalization. Whole genome shotgun sequencing methods were used to process samples. DiffCoEx was used to identify clusters of microbial features significantly …

Prospective Association Of Daily Steps With Cardiovascular Disease: A Harmonized Meta-Analysis, Amanda E Paluch, Shivangi Bajpai, Marcel Ballin, David R Bassett, Thomas W Buford, Mercedes R Carnethon, Ariel Chernofsky, Erin E Dooley, Ulf Ekelund, Kelly R Evenson, Deborah A Galuska, Barbara J Jefferis, Lingsong Kong, William E Kraus, Martin G Larson, I-Min Lee, Charles E Matthews, Robert L Newton, Anna Nordström, Peter Nordström, Priya Palta, Alpa V Patel, Kelley Pettee Gabriel, Carl F Pieper, Lisa Pompeii, Erika Rees-Punia, Nicole L Spartano, Ramachandran S Vasan, Peter H Whincup, Shengping Yang, Janet E Fulton, Steps For Health Collaborative

Faculty, Staff and Students Publications

Background: Taking fewer than the widely promoted "10 000 steps per day" has recently been associated with lower risk of all-cause mortality. The relationship of steps and cardiovascular disease (CVD) risk remains poorly described. A meta-analysis examining the dose-response relationship between steps per day and CVD can help inform clinical and public health guidelines.

Methods: Eight prospective studies (20 152 adults [ie, ≥18 years of age]) were included with device-measured steps and participants followed for CVD events. Studies quantified steps per day and CVD events were defined as fatal and nonfatal coronary heart disease, stroke, and heart failure. Cox proportional …

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

Faculty, Staff and Students Publications

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

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

Excretory/Secretory Proteome Of Females And Males Of The Hookworm Ancylostoma Ceylanicum, Samuel C Uzoechi, Bruce A Rosa, Kumar Sachin Singh, Young-Jun Choi, Bethany K Bracken, Paul J Brindley, R Reid Townsend, Robert Sprung, Bin Zhan, Maria-Elena Bottazzi, John M Hawdon, Yide Wong, Alex Loukas, Sergej Djuranovic, Makedonka Mitreva

Faculty, Staff and Students Publications

The dynamic host-parasite mechanisms underlying hookworm infection establishment and maintenance in mammalian hosts remain poorly understood but are primarily mediated by hookworm’s excretory/secretory products (ESPs), which have a wide spectrum of biological functions. We used ultra-high performance mass spectrometry to comprehensively profile and compare female and male ESPs from the zoonotic human hookworm Ancylostoma ceylanicum, which is a natural parasite of dogs, cats, and humans. We improved the genome annotation, decreasing the number of protein-coding genes by 49% while improving completeness from 92 to 96%. Compared to the previous genome annotation, we detected 11% and 10% more spectra in …

Family Income And Cardiovascular Disease Risk In American Adults, Abdul Mannan Khan Minhas, Vardhmaan Jain, Monica Li, Robert W Ariss, Marat Fudim, Erin D Michos, Salim S Virani, Laurence Sperling, Anurag Mehta

Faculty, Staff and Students Publications

Socioeconomic status is an overlooked risk factor for cardiovascular disease (CVD). Low family income is a measure of socioeconomic status and may portend greater CVD risk. Therefore, we assessed the association of family income with cardiovascular risk factor and disease burden in American adults. This retrospective analysis included data from participants aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) cycles between 2005 and 2018. Family income to poverty ratio (PIR) was calculated by dividing family (or individual) income by poverty guidelines specific to the survey year and used as a measure of socioeconomic status. The …

A Low-Fat/Sucrose Diet Rich In Complex Carbohydrates Reverses High-Fat/Sucrose Diet-Induced Corneal Dysregulation, Prince K Akowuah, Carolina Lema, Rolando E Rumbaut, Alan R Burns

Faculty, Staff and Students Publications

High-fat/sucrose diet feeding in mice causes loss of corneal nerve function and impairs corneal wound healing. While changing to a diet with a low fat/sugar composition and enrichments in complex carbohydrates mitigates the reduction in nerve function, it remains to be determined if it has an effect on corneal wound healing. In this study, 6-week-old C57BL/6 male mice were fed either a normal diet or a high-fat/sucrose diet for 20 weeks. A third group (diet reversal) was placed on a high-fat/sucrose diet for 10 weeks followed by a normal diet for an additional 10 weeks. A central corneal epithelial abrasion …

Mitochondrial Dysfunction Reactivates Α-Fetoprotein Expression That Drives Copper-Dependent Immunosuppression In Mitochondrial Disease Models, Kimberly A Jett, Zakery N Baker, Amzad Hossain, Aren Boulet, Paul A Cobine, Sagnika Ghosh, Philip Ng, Orhan Yilmaz, Kris Barreto, John Decoteau, Karen Mochoruk, George N Ioannou, Christopher Savard, Sai Yuan, Osama Hmh Abdalla, Christopher Lowden, Byung-Eun Kim, Hai-Ying Mary Cheng, Brendan J Battersby, Vishal M Gohil, Scot C Leary

Faculty, Staff and Students Publications

Signaling circuits crucial to systemic physiology are widespread, yet uncovering their molecular underpinnings remains a barrier to understanding the etiology of many metabolic disorders. Here, we identified a copper-linked signaling circuit activated by disruption of mitochondrial function in the murine liver or heart that resulted in atrophy of the spleen and thymus and caused a peripheral white blood cell deficiency. We demonstrated that the leukopenia was caused by α-fetoprotein, which required copper and the cell surface receptor CCR5 to promote white blood cell death. We further showed that α-fetoprotein expression was upregulated in several cell types upon inhibition of oxidative …

Increased Camkk2 Expression Is An Adaptive Response That Maintains The Fitness Of Tumor-Infiltrating Natural Killer Cells, Patrick K Juras, Luigi Racioppi, Debarati Mukherjee, Sandeep Artham, Xia Gao, Laura Akullian D'Agostino, Ching-Yi Chang, Donald P Mcdonnell

Faculty, Staff and Students Publications

Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a key regulator of energy homeostasis in several cell types. Expression of this enzyme in tumor cells promotes proliferation and migration, and expression in tumor-associated immune cells facilitates M2 macrophage polarization and the development of myeloid-derived suppressor cells. Thus, there has been interest in developing CaMKK2 inhibitors as potential anticancer therapeutics. One impediment to clinical development of these agents is that the roles of CaMKK2 in other cellular compartments within the tumor immune microenvironment remain to be established. We report herein that CaMKK2 is expressed at low basal levels in natural killer (NK) …

Inverse Association Between Gluteofemoral Obesity And Risk Of Non-Cardia Gastric Intestinal Metaplasia, Andre G Jove, Hudson M Holmes, Mimi C Tan, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND & AIMS: It is unclear whether obesity confers increased risk of non-cardia gastric adenocarcinoma and its precursor, gastric intestinal metaplasia. Here, we examined whether various dimensions of adiposity independently predispose to the development of non-cardia gastric intestinal metaplasia.

METHODS: We compared data from 409 non-cardia gastric intestinal metaplasia cases and 1748 controls without any gastric intestinal metaplasia from a cross-sectional study at the VA Medical Center in Houston, Texas. Participants completed standardized questionnaires, underwent anthropometric measurements, and underwent a study endoscopy with gastric mapping biopsies. Non-cardia gastric intestinal metaplasia cases included participants with intestinal metaplasia on any non-cardia gastric …

Intermel: An International Biorepository And Clinical Database To Uncover Predictors Of Survival In Early-Stage Melanoma, Irene Orlow, Keimya D Sadeghi, Sharon N Edmiston, Jessica M Kenney, Cecilia Lezcano, James S Wilmott, Anne E Cust, Richard A Scolyer, Graham J Mann, Tim K Lee, Hazel Burke, Valerie Jakrot, Ping Shang, Peter M Ferguson, Tawny W Boyce, Jennifer S Ko, Peter Ngo, Pauline Funchain, Judy R Rees, Kelli O'Connell, Honglin Hao, Eloise Parrish, Kathleen Conway, Paul B Googe, David W Ollila, Stergios J Moschos, Eva Hernando, Douglas Hanniford, Diana Argibay, Christopher I Amos, Jeffrey E Lee, Iman Osman, Li Luo, Pei-Fen Kuan, Arshi Aurora, Bonnie E Gould Rothberg, Marcus W Bosenberg, Meg R Gerstenblith, Cheryl Thompson, Paul N Bogner, Ivan P Gorlov, Sheri L Holmen, Elise K Brunsgaard, Yvonne M Saenger, Ronglai Shen, Venkatraman Seshan, Eduardo Nagore, Marc S Ernstoff, Klaus J Busam, Colin B Begg, Nancy E Thomas, Marianne Berwick, Intermel Consortium

Faculty, Staff and Students Publications

INTRODUCTION: We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium.

METHODS: Following a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for …