Life Sciences Commons^™

Perfluorooctanoic Acid (Pfoa) Or Perfluorooctane Sulfonate (Pfos) And Dna Methylation In Newborn Dried Blood Spots In The Upstate Kids Cohort, Sonia L Robinson, Xuehuo Zeng, Weihua Guan, Rajeshwari Sundaram, Pauline Mendola, Diane L Putnick, Robert A Waterland, Chathura J Gunasekara, Kurunthachalam Kannan, Chongjing Gao, Erin M Bell, Edwina H Yeung

Children’s Nutrition Research Center Staff Publications

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are persistent organic pollutants which may alter prenatal development, potentially through epigenetic modifications. Prior studies examining PFOS/PFOA and DNA methylation have relatively few subjects (n < 200) and inconsistent results. We examined relations of PFOA/PFOS with DNA methylation among 597 neonates in the Upstate KIDS cohort study. PFOA/PFOS were quantified in newborn dried blood spots (DBS) using high-performance liquid chromatography/tandem mass spectrometry. DNA methylation was measured using the Infinium MethylationEPIC BeadChip with DNA extracted from DBS. Robust linear regression was used to examine the associations of PFOA/PFOS with DNA methylation at individual CpG sites. Covariates included sample plate, estimated cell type, epigenetically derived ancestry, infant sex and plurality, indicators of maternal socioeconomic status, and prior pregnancy loss. In supplemental analysis, we restricted the analysis to 2242 CpG sites previously identified as Correlated Regions of Systemic Interindividual Variation (CoRSIVs) which include metastable epialleles. At FDR90th percentile was related to DNA methylation at cg15557840, near SCRT2, SRXN1; PFOS>90th percentile was related to 2 CpG sites in a sex-specific manner (cg19039925 in GVIN1 in boys and cg05754408 in ZNF26 in girls). When analysis was restricted to CoRSIVs, log-scaled, continuous PFOS concentration was related to DNA methylation at cg03278866 within PTBP1. In conclusion, there was limited evidence of an association between high concentrations of PFOA/PFOS and DNA methylation in newborn DBS in the Upstate KIDS cohort. These …

Metabolic Flexibility Across The Spectrum Of Glycemic Regulation In Youth, Fida Bacha, Sara Klinepeter Bartz, Maurice Puyau, Anne Adolph, Susan Sharma

Children’s Nutrition Research Center Staff Publications

BACKGROUNDMetabolic flexibility (MF) refers to the relative ability to utilize lipid and carbohydrate substrates and to transition between them. It is not clear whether MF is impaired in obese youth and what the determining factors are.METHODSWe investigated the determinants of MF (increased respiratory exchange ratio [ΔRER] under insulin-stimulated conditions) in pubertal youth (n = 104; 15.6 ± 1.8 years) with obesity across the spectrum of glucose tolerance compared with normal weight (NW) controls, including body composition (fat-free mass [FFM], %body fat), visceral adipose fat (VAT) (MRI), glycemia, and insulin sensitivity (IS) [3-hour hyperinsulinemic-euglycemic clamp with measurement of lipolysis ([2H5] glycerol), …

A Standard Calculation Methodology For Human Doubly Labeled Water Studies, John R Speakman, Yosuke Yamada, Hiroyuki Sagayama, Elena S F Berman, Philip N Ainslie, Lene F Andersen, Liam J Anderson, Lenore Arab, Issaad Baddou, Kweku Bedu-Addo, Ellen E Blaak, Stephane Blanc, Alberto G Bonomi, Carlijn V C Bouten, Pascal Bovet, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Graeme L Close, Jamie A Cooper, Seth A Creasy, Sai Krupa Das, Richard Cooper, Lara R Dugas, Cara B Ebbeling, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Annelies H Goris, Michael Gurven, Catherine Hambly, Asmaa El Hamdouchi, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Kitty P Kempen, Misaka Kimura, William E Kraus, Robert F Kushner, Estelle V Lambert, William R Leonard, Nader Lessan, David S Ludwig, Corby K Martin, Anine C Medin, Erwin P Meijer, James C Morehen, James P Morton, Marian L Neuhouser, Theresa A Nicklas, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Roberto A Rabinovich, Susan B Racette, David A Raichlen, Eric Ravussin, Rebecca M Reynolds, Susan B Roberts, Albertine J Schuit, Anders M Sjödin, Eric Stice, Samuel S Urlacher, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, Jonathan C K Wells, George Wilson, Brian M Wood, Jack Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Cornelia U Loechl, Edward L Melanson, Amy H Luke, Herman Pontzer, Jennifer Rood, Dale A Schoeller, Klaas R Westerterp, William W Wong

Children’s Nutrition Research Center Staff Publications

The doubly labeled water (DLW) method measures total energy expenditure (TEE) in free-living subjects. Several equations are used to convert isotopic data into TEE. Using the International Atomic Energy Agency (IAEA) DLW database (5,756 measurements of adults and children), we show considerable variability is introduced by different equations. The estimated rCO2 is sensitive to the dilution space ratio (DSR) of the two isotopes. Based on performance in validation studies, we propose a new equation based on a new estimate of the mean DSR. The DSR is lower at low body masses (<10 kg). Using data for 1,021 babies and infants, we show that the DSR varies non-linearly with body mass between 0 and 10 kg. Using this relationship to predict DSR from weight provides an equation for rCO2 over this size range that agrees well with indirect calorimetry (average difference 0.64%; SD = 12.2%). We propose adoption of these equations in future studies.

Genetic Variants And Physical Activity Interact To Affect Bone Density In Hispanic Children, Ruixue Hou, Shelley A Cole, Mariaelisa Graff, Yujie Wang, Karin Haack, Sandra Laston, Nitesh R Mehta, Roman J Shypailo, Margaret L Gourlay, Anthony G Comuzzie, Kari E North, Nancy F Butte, Venkata Saroja Voruganti

Children’s Nutrition Research Center Staff Publications

Background: Our aim was to investigate if moderate to vigorous physical activity (MVPA), calcium intake interacts with bone mineral density (BMD)-related single nucleotide polymorphisms (SNPs) to influence BMD in 750 Hispanic children (4-19y) of the cross-sectional Viva La Familia Study.

Methods: Physical activity and dietary intake were measured by accelerometers and multiple-pass 24 h dietary recalls, respectively. Total body and lumbar spine BMD were measured by dual energy X-ray absorptiometry. A polygenic risk score (PRS) was computed based on SNPs identified in published literature. Regression analysis was conducted with PRSs, MVPA and calcium intake with total body and lumbar spine …

Parenteral Lipid Emulsions Induce Unique Ileal Fatty Acid And Metabolomic Profiles But Do Not Increase The Risk Of Necrotizing Enterocolitis In Preterm Pigs, William Yakah, Pratibha Singh, Joanne Brown, Barbara Stoll, Doug Burrin, Muralidhar H Premkumar, Hasan H Otu, Xuesong Gu, Simon T Dillon, Towia A Libermann, Steven D Freedman, Camilia R Martin

Children’s Nutrition Research Center Staff Publications

Necrotizing enterocolitis (NEC) is a manifestation of maladaptive intestinal responses in preterm infants centrally medicated by unattenuated inflammation. Early in the postnatal period, preterm infants develop a deficit in arachidonic and docosahexaenoic acid, both potent regulators of inflammation. We hypothesized that the fatty acid composition of parenteral lipid emulsions uniquely induces blood and intestinal fatty acid profiles which, in turn, modifies the risk of NEC development. Forty-two preterm pigs were randomized to receive one of three lipid emulsions containing 100% soybean oil (SO), 15% fish oil (MO15), or 100% fish oil (FO100) with enteral feedings over an 8-day protocol. Blood …

Rationale And Design Of The Baylor Infant Twin Study-A Study Assessing Obesity-Related Risk Factors From Infancy, Shabnam R Momin, Mackenzie K Senn, Scott Buckley, Neil R M Buist, Manisha Gandhi, Amy B Hair, Sheryl O Hughes, Kelly R Hodges, William C Lange, Maria A Papaioannou, Mimi Phan, Robert A Waterland, Alexis C Wood

Children’s Nutrition Research Center Staff Publications

Background: Early childhood (0-3 years) is a critical period for obesity prevention, when tendencies in eating behaviors and physical activity are established. Yet, little is understood about how the environment shapes children's genetic predisposition for these behaviors during this time. The Baylor Infant Twin Study (BITS) is a two phase study, initiated to study obesity risk factors from infancy. Data collection has been completed for Phase 1 in which three sub-studies pilot central measures for Phase 2. A novel infant temperament assessment, based on observations made by trained researchers was piloted in Behavior Observation Pilot Protocol (BOPP) study, a new …

Fructan-Sensitive Children With Irritable Bowel Syndrome Have Distinct Gut Microbiome Signatures, Bruno P Chumpitazi, Kristi L Hoffman, Daniel P Smith, Ann R Mcmeans, Salma Musaad, James Versalovic, Joseph F Petrosino, Robert J Shulman

Children’s Nutrition Research Center Staff Publications

Background: Dietary fructans may worsen gastrointestinal symptoms in children with irritable bowel syndrome (IBS).

Aim: To determine whether gut microbiome composition and function are associated with childhood IBS fructan-induced symptoms.

Methods: Faecal samples were collected from 38 children aged 7-17 years with paediatric Rome III IBS, who previously completied a double-blind, randomised, placebo-controlled crossover (fructan vs maltodextrin) trial. Fructan sensitivity was defined as an increase of ≥30% in abdominal pain frequency during the fructan diet. Gut microbial composition was determined via 16Sv4 rDNA sequencing. LEfSe evaluated taxonomic composition differences. Tax4Fun2 predicted microbial fructan metabolic pathways.

Results: At baseline, 17 fructan-sensitive …

Overview Of Breath Testing In Clinical Practice In North America, Buford L Nichols, Robert D Baker, Susan S Baker

Children’s Nutrition Research Center Staff Publications

Human breath is an easily, noninvasively obtained substance. It offers insight into metabolism and is used to diagnose disaccharide malabsorption, infection, small bowel bacterial over growth, and transit times. Herein, we discuss the readily available clinical breath tests, how they function, how they are administered and interpreted and some pitfalls in their use.

Genome-Wide Meta-Analysis Of Muscle Weakness Identifies 15 Susceptibility Loci In Older Men And Women, Garan Jones, Katerina Trajanoska, Adam J Santanasto, Najada Stringa, Chia-Ling Kuo, Janice L Atkins, Joshua R Lewis, Thuyvy Duong, Shengjun Hong, Mary L Biggs, Jian'an Luan, Chloe Sarnowski, Kathryn L Lunetta, Toshiko Tanaka, Mary K Wojczynski, Ryan Cvejkus, Maria Nethander, Sahar Ghasemi, Jingyun Yang, M Carola Zillikens, Stefan Walter, Kamil Sicinski, Erika Kague, Cheryl L Ackert-Bicknell, Dan E Arking, B Gwen Windham, Eric Boerwinkle, Megan L Grove, Misa Graff, Dominik Spira, Ilja Demuth, Nathalie Van Der Velde, Lisette C P G M De Groot, Bruce M Psaty, Michelle C Odden, Alison E Fohner, Claudia Langenberg, Nicholas J Wareham, Stefania Bandinelli, Natasja M Van Schoor, Martijn Huisman, Qihua Tan, Joseph Zmuda, Dan Mellström, Magnus Karlsson, David A Bennett, Aron S Buchman, Philip L De Jager, Andre G Uitterlinden, Uwe Völker, Thomas Kocher, Alexander Teumer, Leocadio Rodriguéz-Mañas, Francisco J García, José A Carnicero, Pamela Herd, Lars Bertram, Claes Ohlsson, Joanne M Murabito, David Melzer, George A Kuchel, Luigi Ferrucci, David Karasik, Fernando Rivadeneira, Douglas P Kiel, Luke C Pilling

Faculty, Staff and Student Publications

Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1 p = 4 × 10

Absent B Cells, Agammaglobulinemia, And Hypertrophic Cardiomyopathy In Folliculin-Interacting Protein 1 Deficiency, Francesco Saettini, Cecilia Poli, Jaime Vengoechea, Sonia Bonanomi, Julio C Orellana, Grazia Fazio, Fred H Rodriguez, Loreani P Noguera, Claire Booth, Valentina Jarur-Chamy, Marissa Shams, Maria Iascone, Maja Vukic, Serena Gasperini, Manuel Quadri, Amairelys Barroeta Seijas, Elizabeth Rivers, Mario Mauri, Raffaele Badolato, Gianni Cazzaniga, Cristina Bugarin, Giuseppe Gaipa, Wilma G M Kroes, Daniele Moratto, Monique M Van Oostaijen-Ten Dam, Frank Baas, Silvère Van Der Maarel, Rocco Piazza, Zeynep H Coban-Akdemir, James R Lupski, Bo Yuan, Ivan K Chinn, Lucia Daxinger, Andrea Biondi

Faculty, Staff and Student Publications

Agammaglobulinemia is the most profound primary antibody deficiency that can occur due to an early termination of B-cell development. We here investigated 3 novel patients, including the first known adult, from unrelated families with agammaglobulinemia, recurrent infections, and hypertrophic cardiomyopathy (HCM). Two of them also presented with intermittent or severe chronic neutropenia. We identified homozygous or compound-heterozygous variants in the gene for folliculin interacting protein 1 (FNIP1), leading to loss of the FNIP1 protein. B-cell metabolism, including mitochondrial numbers and activity and phosphatidylinositol 3-kinase/AKT pathway, was impaired. These defects recapitulated the Fnip1-/- animal model. Moreover, we identified either uniparental disomy …

Exchanges In A Virtual Environment For Diabetes Self-Management Education And Support: Social Network Analysis, Carlos A Pérez-Aldana, Allison A Lewinski, Constance M Johnson, Allison A Vorderstrasse, Sahiti Myneni

Faculty, Staff and Student Publications

BACKGROUND: Diabetes remains a major health problem in the United States, affecting an estimated 10.5% of the population. Diabetes self-management interventions improve diabetes knowledge, self-management behaviors, and clinical outcomes. Widespread internet connectivity facilitates the use of eHealth interventions, which positively impacts knowledge, social support, and clinical and behavioral outcomes. In particular, diabetes interventions based on virtual environments have the potential to improve diabetes self-efficacy and support, while being highly feasible and usable. However, little is known about the patterns of social interactions and support taking place within type 2 diabetes-specific virtual communities.

OBJECTIVE: The objective of this study was to …

Parenteral Fish-Oil Containing Lipid Emulsions Limit Initial Lipopolysaccharide-Induced Host Immune Responses In Preterm Pigs, William Yakah, David Ramiro-Cortijo, Pratibha Singh, Joanne Brown, Barbara Stoll, Madhulika Kulkarni, Berthe C Oosterloo, Doug Burrin, Krishna Rao Maddipati, Raina N Fichorova, Steven D Freedman, Camilia R Martin

Children’s Nutrition Research Center Staff Publications

Multicomponent lipid emulsions are available for critical care of preterm infants. We sought to determine the impact of different lipid emulsions on early priming of the host and its response to an acute stimulus. Pigs delivered 7d preterm (n = 59) were randomized to receive different lipid emulsions for 11 days: 100% soybean oil (SO), mixed oil emulsion (SO, medium chain olive oil and fish oil) including 15% fish oil (MO15), or 100% fish oil (FO100). On day 11, pigs received an 8-h continuous intravenous infusion of either lipopolysaccharide (LPS—lyophilized Escherichia coli) or saline. Plasma was collected for …

Agrp Neurons Trigger Long-Term Potentiation And Facilitate Food Seeking, Chunmei Wang, Wenjun Zhou, Yang He, Tiffany Yang, Pingwen Xu, Yongjie Yang, Xing Cai, Julia Wang, Hesong Liu, Meng Yu, Chen Liang, Tingting Yang, Hailan Liu, Makoto Fukuda, Qingchun Tong, Qi Wu, Zheng Sun, Yanlin He, Yong Xu

Children’s Nutrition Research Center Staff Publications

Sufficient feeding is essential for animals' survival, which requires a cognitive capability to facilitate food seeking, but the neurobiological processes regulating food seeking are not fully understood. Here we show that stimulation of agouti-related peptide-expressing (AgRP) neurons triggers a long-term depression (LTD) of spontaneous excitatory post-synaptic current (sEPSC) in adjacent pro-opiomelanocortin (POMC) neurons and in most of their distant synaptic targets, including neurons in the paraventricular nucleus of the thalamus (PVT). The AgRP-induced sEPCS LTD can be enhanced by fasting but blunted by satiety signals, e.g. leptin and insulin. Mice subjected to food-seeking tasks develop similar neural plasticity in AgRP-innervated …

Identifying Sleep-Related Factors Associated With Cognitive Function In A Hispanics/Latinos Cohort: A Dual Random Forest Approach, Li Xiaojin, Cui Licong, Wang Fei, Paul E Schulz, Guo-Qiang Zhang

Faculty, Staff and Student Publications

Disordered sleep is associated with poor cognitive function and cognitive decline. However, little is known regarding the association of sleep-related factors with cognitive function in underrepresented cohorts such as the Hispanic/Latino population. Leveraging the National Sleep Research Resource, one of the most comprehensive collections of sleep studies, we identified a Hispanic/Latino cohort of 1,031 lower cognitive function cases and 2,062 normal controls. We developed a novel dual random forest (DRF) approach to discriminate cases against controls for estimating the potential impact of sleep-related variables related to the decline of cognitive function. Several important sleep-related factors were identified which may be …

Towards Digestible Digital Health Solutions: Application Of A Health Literacy Inclusive Development Framework For Peripartum Depression Management, Alexandra Zingg, Tavleen Singh, Sahiti Myneni

Faculty, Staff and Student Publications

Women of low income and education have lower levels of peripartum depression (PPD) literacy, limiting their ability to recognize symptoms and make informed healthcare decisions. Existing digital solutions and underlying development frameworks for PPD lack an integrative approach addressing health literacy and related disparities. Therefore, we develop an integrative framework for digital content engineering in PPD self-management consisting of (a) user needs analysis, (b) inclusion of eHealth literacy principles (science and health literacy), and (c) mapping user needs to the Behavioral Intervention Technology model. Results revealed that perinatal women seeking mental health care prefer information in multisensory formats, and knowledge …

A Comparison Of Exhaustive And Non-Lattice-Based Methods For Auditing Hierarchical Relations In Gene Ontology, Rashmie Abeysinghe, Fengbo Zheng, Licong Cui

Faculty, Staff and Student Publications

Uncovering and fixing errors in biomedical terminologies is essential so that they provide accurate knowledge to downstream applications that rely on them. Non-lattice-based methods have been applied to identify various kinds of inconsistencies in different biomedical terminologies. In previous work, we have introduced two inference-based approaches that were applied in an exhaustive manner to audit hierarchical relations in the Gene Ontology: (1) Lexical-based inference framework, and (2) Subsumption-based sub-term inference framework. However, it is unclear how effective these exhaustive approaches perform compared with their corresponding non-lattice-based approaches. Therefore, in this paper, we implement the non-lattice versions of these two exhaustive …

Science Dialogue Mapping Of Knowledge And Knowledge Gaps Related To The Effects Of Dairy Intake On Human Cardiovascular Health And Disease, Andrew W Brown, Kathryn A Kaiser, Andrew Keitt, Kevin Fontaine, Madeline Gibson, Barbara A Gower, James M Shikany, Colby J Vorland, Donald C Beitz, Dennis M Bier, J Thomas Brenna, David R Jacobs, Penny Kris-Etherton, Kevin Maki, Michael Miller, Marie-Pierre St-Onge, Margarita Teran-Garcia, David B Allison

Children’s Nutrition Research Center Staff Publications

Dairy has been described as everything from a superfood to a poison; yet, arguments, assumptions, and data justifying these labels are not always clear. We used an issue-based information system, “dialogue mapping™,” to summarize scientific points of a live panel discussion on the putative effects of dairy on cardiovascular diseases (CVD) from a day-long session among experts in nutrition and CVD. Dialogue mapping captures relations among ideas to explicitly, logically, and visually connect issues/questions, ideas, pro/con arguments, and agreements, even if discussed at different times. Experts discussed two propositions: for CVD risk, consumption of full-fat dairy products, 1) should be …

Tph2 In The Dorsal Raphe Nuclei Regulates Energy Balance In A Sex-Dependent Manner, Hailan Liu, Chunmei Wang, Meng Yu, Yongjie Yang, Yang He, Hesong Liu, Chen Liang, Longlong Tu, Nan Zhang, Lina Wang, Julia Wang, Feng Liu, Fang Hu, Yong Xu

Children’s Nutrition Research Center Staff Publications

AbstractCentral 5-hydroxytryptamine (5-HT), which is primarily synthesized by tryptophan hydroxylase 2 (TPH2) in the dorsal Raphe nuclei (DRN), plays a pivotal role in the regulation of food intake and body weight. However, the physiological functions of TPH2 on energy balance have not been consistently demonstrated. Here we systematically investigated the effects of TPH2 on energy homeostasis in adult male and female mice. We found that the DRN harbors a similar amount of TPH2+ cells in control male and female mice. Adult-onset TPH2 deletion in the DRN promotes hyperphagia and body weight gain only in male mice, but not in female …

Hypothalamic Perineuronal Nets Are Regulated By Sex And Dietary Interventions, Nan Zhang, Zili Yan, Hailan Liu, Meng Yu, Yang He, Hesong Liu, Chen Liang, Longlong Tu, Lina Wang, Na Yin, Junying Han, Nikolas Scarcelli, Yongjie Yang, Chunmei Wang, Tianshu Zeng, Lu-Lu Chen, Yong Xu

Children’s Nutrition Research Center Staff Publications

Perineuronal nets (PNNs) are widely present in the hypothalamus, and are thought to provide physical protection and ion buffering for neurons and regulate their synaptic plasticity and intracellular signaling. Recent evidence indicates that PNNs in the mediobasal hypothalamus play an important role in the regulation of glucose homeostasis. However, whether and how hypothalamic PNNs are regulated are not fully understood. In the present study, we examined whether PNNs in various hypothalamic regions in mice can be regulated by sex, gonadal hormones, dietary interventions, or their interactions. We demonstrated that gonadal hormones are required to maintain normal PNNs in the arcuate …

Associations Between Independent Assessments Of Child Appetite Self-Regulation: A Narrative Review, Maria A Papaioannou, Nilda Micheli, Thomas G Power, Jennifer O Fisher, Sheryl O Hughes

Children’s Nutrition Research Center Staff Publications

A variety of eating behaviors among children have been associated with obesity risk and are thought to broadly reflect child appetite self-regulation (ASR). While ASR is thought to occur on cognitive, emotional, motivational, biological, and behavioral levels, the inter-relatedness of ASR constructs as assessed by different methods/measures is not well-characterized. This narrative review describes the correspondence between different methods/measures of child ASR constructs as assessed by self-report questionnaires and/or observational tasks and their relationship to child standardized body mass index (BMIz). Research involving at least two different methods/measures is presented including observational tasks such as the Eating in the Absence …

Crucial Role Of Mammalian Glutaredoxin 3 In Cardiac Energy Metabolism In Diet-Induced Obese Mice Revealed By Transcriptome Analysis, Ninghui Cheng, Qianxing Mo, Jimmonique Donelson, Lingfei Wang, Ghislain Breton, George G Rodney, Jin Wang, Kendal D Hirschi, Xander H T Wehrens, Paul A Nakata

Children’s Nutrition Research Center Staff Publications

Obesity is often associated with metabolic dysregulation and oxidative stress with the latter serving as a possible unifying link between obesity and cardiovascular complications. Glutaredoxins (Grxs) comprise one of the major antioxidant systems in the heart. Although Grx3 has been shown to act as an endogenous negative regulator of cardiac hypertrophy and heart failure, its metabolic impact on cardiac function in diet-induced obese (DIO) mice remains largely unknown. In the present study, analysis of Grx3 expression indicated that Grx3 protein levels, but not mRNA levels, were significantly increased in the hearts of DIO mice. Cardiac-specific Grx3 deletion (Grx3 CKO) mice …

Wearable Activity Tracking Device Use In An Adolescent Weight Management Clinic: A Randomized Controlled Pilot Trial, Kanika Bowen-Jallow, Omar Nunez-Lopez, Alex Wright, Erika Fuchs, Mollie Ahn, Elizabeth Lyons, Daniel Jupiter, Lindsey Berry, Oscar Suman, Ravi S Radhakrishnan, Andrea M Glaser, Deborah I Thompson

Children’s Nutrition Research Center Staff Publications

Background: The use of physical activity tracker devices has increased within the general population. However, there is limited medical literature studying the efficacy of such devices in adolescents with obesity. In this study, we explored the feasibility of using wearable activity tracking devices as an adjunct intervention on adolescents with obesity.

Methods: Randomized controlled pilot trial evaluated the feasibility (attrition ≤50%) of an activity tracking intervention (ATI) and its effects on weight loss in adolescents with obesity enrolled in an adolescent weight management clinic (AWMC). Outcomes included feasibility (attrition rate) and absolute change in BMI. Differences between groups at 6, …

Associations Between Lipoprotein Subfractions And Area And Density Of Abdominal Muscle And Intermuscular Adipose Tissue: The Multi-Ethnic Study Of Atherosclerosis, Megan M Marron, Matthew Allison, Alka M Kanaya, Britta Larsen, Alexis C Wood, David Herrington, Philip Greenland, Iva Miljkovic

Children’s Nutrition Research Center Staff Publications

Skeletal muscle quantity and quality decrease with older age, which is partly attributed to ectopic fat infiltration and has negative metabolic consequences. To inform efforts to preserve skeletal muscle with aging, a better understanding of biologic correlates of quantity and quality of muscle and intermuscular adipose tissue (IMAT) is needed. We used targeted lipidomics of lipoprotein subfractions among 947 Multi-Ethnic Study of Atherosclerosis participants to provide a detailed metabolic characterization of area and density of abdominal muscle and IMAT. Serum lipoprotein subfractions were measured at the first visit using 1H-Nuclear Magnetic Resonance spectroscopy. Muscle and IMAT area (cm

A Computational Pipeline To Infer Alternative Poly-Adenylation From 3′ Sequencing Data, Hari Krishna Yalamanchili, Nathan D Elrod, Madeline K Jensen, Ping Ji, Ai Lin, Eric J Wagner, Zhandong Liu

Children’s Nutrition Research Center Staff Publications

An increasing number of investigations have established alternative polyadenylation (APA) as a key mechanism of gene regulation through altering the length of 3' untranslated region (UTR) and generating distinct mRNA termini. Further, appreciation for the significance of APA in disease contexts propelled the development of several 3' sequencing techniques. While these RNA sequencing technologies have advanced APA analysis, the intrinsic limitation of 3' read coverage and lack of appropriate computational tools constrain precise mapping and quantification of polyadenylation sites. Notably, Poly(A)-ClickSeq (PAC-seq) overcomes limiting factors such as poly(A) enrichment and 3' linker ligation steps using click-chemistry. Here we provide an …

Food/Non-Food Classification Of Real-Life Egocentric Images In Low- And Middle-Income Countries Based On Image Tagging Features, Guangzong Chen, Wenyan Jia, Yifan Zhao, Zhi-Hong Mao, Benny Lo, Alex K Anderson, Gary Frost, Modou L Jobarteh, Megan A Mccrory, Edward Sazonov, Matilda Steiner-Asiedu, Richard S Ansong, Thomas Baranowski, Lora Burke, Mingui Sun

Children’s Nutrition Research Center Staff Publications

Malnutrition, including both undernutrition and obesity, is a significant problem in low- and middle-income countries (LMICs). In order to study malnutrition and develop effective intervention strategies, it is crucial to evaluate nutritional status in LMICs at the individual, household, and community levels. In a multinational research project supported by the Bill & Melinda Gates Foundation, we have been using a wearable technology to conduct objective dietary assessment in sub-Saharan Africa. Our assessment includes multiple diet-related activities in urban and rural families, including food sources (e.g., shopping, harvesting, and gathering), preservation/storage, preparation, cooking, and consumption (e.g., portion size and nutrition analysis). …

On The Joint Role Of Non-Hispanic Black Race/Ethnicity And Weight Status In Predicting Postmenopausal Weight Gain, Christopher N Ford, Shine Chang, Alexis C Wood, Joann E Manson, David O Garcia, Helena Laroche, Chloe E Bird, Mara Z Vitolins

Children’s Nutrition Research Center Staff Publications

Objectives: To determine how baseline weight status contributes to differences in postmenopausal weight gain among non-Hispanic Blacks (NHBs) and non-Hispanic Whites (NHWs).

Methods: Data were included from 70,750 NHW and NHB postmenopausal women from the Women's Health Initiative Observational Study (WHI OS). Body Mass Index (BMI) at baseline was used to classify women as having normal weight, overweight, obese class I, obese class II or obese class III. Cox proportional hazards was used to estimate the hazard of a 10% or more increase in weight from baseline.

Results: In both crude and adjusted models, NHBs were more likely to experience …

Gut Microbiota Profiles Of Young South Indian Children: Child Sex-Specific Relations With Growth, Nirupama Shivakumar, Ambily Sivadas, Sarita Devi, Farook Jahoor, John Mclaughlin, Craig P Smith, Anura V Kurpad, Arpita Mukhopadhyay

Children’s Nutrition Research Center Staff Publications

Gut microbiota has been implicated as a modifier of childhood growth. Here, 16S rRNA sequencing-based fecal microbiota profiles of 18-24 month old Indian children were evaluated (n = 41), in relation to their anthropometric parameters, intestinal permeability, body composition and total energy expenditure. Pathway analyses were conducted to assess microbial functions related to stunting, underweight and wasting. The fecal microbiota was enriched in Prevotella 9, Bifidobacterium and Escherichia-Shigella. Weight, weight-for-age Z-scores (WAZ) and weight-for-length Z-scores (WLZ), along with age, acted as covariates of microbiota variation specifically in boys (n = 23). Bifidobacterium longum subsp longum abundance was positively associated with …

Utilization Of Target Lesion Heterogeneity For Treatment Efficacy Assessment In Late Stage Lung Cancer, Dung-Tsa Chen, Wenyaw Chan, Zachary J Thompson, Ram Thapa, Amer A Beg, Andreas N Saltos, Alberto A Chiappori, Jhanelle E Gray, Eric B Haura, Trevor A Rose, Ben Creelan

Faculty, Staff and Student Publications

RATIONALE: Recent studies have discovered several unique tumor response subgroups outside of response classification by Response Evaluation Criteria for Solid Tumors (RECIST), such as mixed response and oligometastasis. These subtypes have a distinctive property, lesion heterogeneity defined as diversity of tumor growth profiles in RECIST target lesions. Furthermore, many cancer clinical trials have been activated to evaluate various treatment options for heterogeneity-related subgroups (e.g., 29 trials so far listed in clinicaltrials.gov for cancer patients with oligometastasis). Some of the trials have shown survival benefit by tailored treatment strategies. This evidence presents the unmet need to incorporate lesion heterogeneity to improve …

Carving The Path To Allogeneic Car T Cell Therapy In Acute Myeloid Leukemia, Oren Pasvolsky, May Daher, Gheath Alatrash, David Marin, Naval Daver, Farhad Ravandi, Katy Rezvani, Elizabeth Shpall, Partow Kebriaei

Faculty, Staff and Student Publications

Despite advances in the understanding of the genetic landscape of acute myeloid leukemia (AML) and the addition of targeted biological and epigenetic therapies to the available armamentarium, achieving long-term disease-free survival remains an unmet need. Building on growing knowledge of the interactions between leukemic cells and their bone marrow microenvironment, strategies to battle AML by immunotherapy are under investigation. In the current review we describe the advances in immunotherapy for AML, with a focus on chimeric antigen receptor (CAR) T cell therapy. CARs constitute powerful immunologic modalities, with proven clinical success in B-Cell malignancies. We discuss the challenges and possible …

Deep Learning For Automated Analysis Of Cellular And Extracellular Components Of The Foreign Body Response In Multiphoton Microscopy Images, Mattia Sarti, Maria Parlani, Luis Diaz-Gomez, Antonios G Mikos, Pietro Cerveri, Stefano Casarin, Eleonora Dondossola

Faculty, Staff and Student Publications

The Foreign body response (FBR) is a major unresolved challenge that compromises medical implant integration and function by inflammation and fibrotic encapsulation. Mice implanted with polymeric scaffolds coupled to intravital non-linear multiphoton microscopy acquisition enable multiparametric, longitudinal investigation of the FBR evolution and interference strategies. However, follow-up analyses based on visual localization and manual segmentation are extremely time-consuming, subject to human error, and do not allow for automated parameter extraction. We developed an integrated computational pipeline based on an innovative and versatile variant of the U-Net neural network to segment and quantify cellular and extracellular structures of interest, which is …