Medical Specialties Commons^™

Impact Of Pediatric Obesity On Diurnal Blood Pressure Assessment And Cardiovascular Risk Markers, Margaret O. Murphy, Hong Huang, John A. Bauer, Aric Schadler, Majd Makhoul, Jody L. Clasey, Aftab S. Chishti, Stefan G. Kiessling

Pediatrics Faculty Publications

Background: The prevalence of hypertension is increasing particularly among obese children and adolescents. Obese children and adolescents with hypertension are likely to remain hypertensive as they reach adulthood and hypertension is linked to an increased risk for cardiovascular disease. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) has become one of the most important tools in diagnosing hypertension in children and adolescents and circadian patterns of blood pressure may be important disease-risk predictors.

Methods: A retrospective chart review was conducted in patients aged 6–21 years who underwent 24-h ABPM at Kentucky Children's Hospital (KCH) from August 2012 through June 2017. Exclusion criteria …

Presence Of Antibody-Dependent Cellular Cytotoxicity (Adcc) Against Sars-Cov-2 In Covid-19 Plasma, For Yue Tso, Salum J. Lidenge, Lisa K. Poppe, Phoebe B. Pena, Sara R. Privatt, Sydney J. Bennett, John R. Ngowi, Julius Mwaiselage, Michael Belshan, Jacob A. Siedlik, Morgan A. Raine, Juan B. Ochoa, Julia Garcia-Diaz, Bobby Nossaman, Lyndsey Buckner, W Mark Roberts, Matthew J. Dean, Augusto C. Ochoa, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Background Neutralizing-antibody (nAb) is the major focus of most ongoing COVID-19 vaccine trials. However, nAb response against SARS-CoV-2, when present, decays rapidly. Given the myriad roles of antibodies in immune responses, it is possible that antibodies could also mediate protection against SARS-CoV-2 via effector mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), which we sought to explore here. Methods Plasma of 3 uninfected controls and 20 subjects exposed to, or recovering from, SARS CoV-2 infection were collected from U.S. and sub-Saharan Africa. Immunofluorescence assay was used to detect the presence of SARS-CoV-2 specific IgG antibodies in the plasma samples. SARS-CoV-2 specific …

Association Of Blood Pressure Variability And Diuretics With Cardiovascular Events In Patients With Chronic Kidney Disease Stages 1-5, L Parker Gregg, S Susan Hedayati, Hui Yang, Peter N Van Buren, Subhash Banerjee, Sankar D Navaneethan, Salim S Virani, Wolfgang C Winkelmayer, Carlos A Alvarez

Faculty, Staff and Students Publications

Visit-to-visit blood pressure variability (BPV) is associated with cardiovascular events in the general population. Data are scarce in chronic kidney disease (CKD). We hypothesized that BPV would be associated with cardiovascular outcomes, death, and end-stage kidney disease (ESKD) and that diuretics would modify these associations in patients with CKD.

We studied U.S. Veterans with non-dialysis CKD stages 1-5 and hypertension on non-diuretic antihypertensive monotherapy. At the time of second antihypertensive agent prescription, we propensity-matched for exposure to a loop or thiazide diuretic vs. any other antihypertensive. BPV was defined as the coefficient of variation of systolic blood pressure over …

Almond Protects The Liver In Coronary Artery Disease: A Randomized Controlled Clinical Trial, Humaira Jamshed, Jamshed Arslan, Fateh Ali Tipoo Sultan, Hasan Salman Siddiqi, Muhammad Qasim, Anwarul Hassan Gilani

Section of Cardiology

Objective: To compare the effect of Pakistani and American almonds on serum concentration of liver enzymes in coronary artery disease patients.
Methods: The randomised controlled trial was conducted at the Cardiology Clinics of Aga Khan University Hospital, Karachi, from February to July, 2012, and comprised patients who were randomised into intervention PA and AA groups and the control NI groups. Subjects in the intervention groups were provided Pakistani and American varieties of almonds 10g/day respectively with instructions to soak them overnight, remove the skin and eat them before breakfast for 12 weeks. The control group underwent no intervention. Serum concentrations …

Evaluation Of Serum Ferritin For Prediction Of Severity And Mortality In Covid-19- A Cross Sectional Study, Sibtain Ahmed, Zeeshan Ansar Ahmed, Imran Siddiqui, Naveed Haroon Rashid, Maheen Mansoor, Lena Jafri

Department of Pathology and Laboratory Medicine

Background: Ferritin even though widely recognized as a representative of total body iron stores, its prognostic utility is linked with COVID-19. This study was aimed at evaluation of the association of ferritin with severity in Coronavirus disease 2019 (COVID-19), hospitalized patients and to test the hypothesis that it is an independent predictor of mortality.
Material and methods: This study was conducted at Chemical Pathology, Department of Pathology and Laboratory Medicine, Aga Khan University (AKU), Karachi. Medical records of all in-patients including both genders, and all age groups with documented COVID-19 from 1st March to 10^th August 2020 were reviewed. …

Inhibition Of Zika Virus Replication By G-Quadruplex-Binding Ligands, Indian Institute Of Technology Indore, Aryamav Pattnaik, Bikash R. Sahoo, Uma Shankar, Asit K. Pattnaik, Amit Kumar, Debasis Nayak

Nebraska Center for Virology: Faculty Publications

Zika virus (ZIKV), a mosquito-transmitted Flavivirus, emerged in the last decade causing serious diseases and affecting human health globally. Currently, no licensed vaccines or antivirals are available to combat ZIKV, although several vaccine candidates are in the pipeline. In recent years, the presence of non-canonical G-quadruplex (GQ) secondary structures in viral genomes has ignited significant attention as potential targets for antiviral strategy. In this study, we identified several novel conserved potential GQ structures by analyzing published ZIKV genome sequences using an in-house algorithm. Biophysical and biochemical analysis of the RNA sequences containing these potential GQ sequences suggested the existence of …

Effect Of Crohn's Disease On Villous Length And Cyp3a4 Expression In The Pediatric Small Intestine., Carrie A. Vyhlidal, Brian D. Chapron, Atif Ahmed, Vivekanand Singh, Rebecca Casini, Valentina Shakhnovich

Manuscripts, Articles, Book Chapters and Other Papers

Changes in absorptive capacity and first-pass metabolism in the small intestine affect oral drug bioavailability. Characterization of such changes as a consequence of inflammation is important for developing physiologically-based pharmacokinetic (PBPK) models for inflammatory bowel disease. We sought to elucidate the impact of small intestinal Crohn's disease (CD) on villous length and CYP3A4 expression in children. Freshly frozen duodenal and terminal ileum (TI) biopsies from 107 children (1-19 years) with and without CD were evaluated for active inflammation. Villous length and CYP3A4 mRNA/protein expression were compared among regions of active and inactive inflammation in CD and controls. A twofold reduction …

Prematurity Blunts The Insulin- And Amino Acid-Induced Stimulation Of Translation Initiation And Protein Synthesis In Skeletal Muscle Of Neonatal Pigs, Marko Rudar, Jane K Naberhuis, Agus Suryawan, Hanh V Nguyen, Barbara Stoll, Candace C Style, Mariatu A Verla, Oluyinka O Olutoye, Douglas G Burrin, Marta L Fiorotto, Teresa A Davis

Children’s Nutrition Research Center Staff Publications

Extrauterine growth restriction in premature infants is largely attributed to reduced lean mass accretion and is associated with long-term morbidities. Previously, we demonstrated that prematurity blunts the feeding-induced stimulation of translation initiation signaling and protein synthesis in skeletal muscle of neonatal pigs. The objective of the current study was to determine whether the blunted feeding response is mediated by reduced responsiveness to insulin, amino acids, or both. Pigs delivered by cesarean section preterm (PT; 103 days,

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 …

Female Genital Tuberculosis In Pakistan - A Retrospective Review Of 10-Year Laboratory Data And Analysis Of 32 Cases, Tazeen Fatima, Rumina Hasan, Faisal Malik, Imran Ahmed, Linda Alice Bartlett, Michael G. Gravett, Sadia Shakoor

Department of Pathology and Laboratory Medicine

Background: Female genital tuberculosis (FGTB) is an underobserved clinical entity owing to diagnostic challenges stemming from difficulty of obtaining diagnostic specimens and paucibacillary nature of the disease. Yet, FGTB is a cause of infertility, pelvic pain, or menstrual irregularities in high-burden countries. To assess laboratory and microbiology diagnostic utilization for FGTB in Pakistan, we have collected data from 2007 to 2016 to inform the need for improved laboratory diagnostics. The objectives of this study were to determine the proportion of FGTB as culture-confirmed extrapulmonary tuberculosis (EPTB) and to describe the characteristics of women with culture-confirmed FGTB in a nationwide laboratory …

Evaluating The Revised American Society For Gastrointestinal Endoscopy Guidelines For Common Bile Duct Stone Diagnosis, Jake S Jacob, Michelle E Lee, Erin Y Chew, Aaron P Thrift, Robert J Sealock

Faculty, Staff and Students Publications

BACKGROUND/AIMS: The American Society for Gastrointestinal Endoscopy (ASGE) revised its guidelines for risk stratification of patients with suspected choledocholithiasis. This study aimed to assess the diagnostic performance of the revision and to compare it to the previous guidelines.

METHODS: We conducted a retrospective cohort study of 267 patients with suspected choledocholithiasis. We identified high-risk patients according to the original and revised guidelines and examined the diagnostic accuracy of both guidelines. We measured the association between individual criteria and choledocholithiasis.

RESULTS: Under the original guidelines, 165 (62%) patients met the criteria for high risk, of whom 79% had confirmed choledocholithiasis. The …

Mental Health Disorders Among Patients With Acute Myocardial Infarction In The United States, Jayakumar Sreenivasan, Muhammad Shahzeb Khan, Safi U Khan, Urvashi Hooda, Wilbert S Aronow, Julio A Panza, Glenn N Levine, Yvonne Commodore-Mensah, Roger S Blumenthal, Erin D Michos

Faculty, Staff and Students Publications

OBJECTIVE: To assess the prevalence, temporal trends and sex- and racial/ethnic differences in the burden of mental health disorders (MHD) and outcomes among patients with myocardial infarction (MI) in the United States.

METHODS: Using the National Inpatient Sample Database, we evaluated a contemporary cohort of patients hospitalized for acute MI in the United States over 10 years period from 2008 to 2017. We used multivariable logistic regression analysis for in-hospital outcomes, yearly trends and estimated annual percent change (APC) in odds of MHD among MI patients.

RESULTS: We included a total sample of 6,117,804 hospitalizations for MI (ST elevation MI …

Ceramide Synthase Tlcd3b Is A Novel Gene Associated With Human Recessive Retinal Dystrophy, Renae Elaine Bertrand, Jun Wang, Kaitlyn H Xiong, Chinthana Thangavel, Xinye Qian, Rola Ba-Abbad, Qingnan Liang, Renata T Simões, Shirley A M Sampaio, Keren J Carss, F Lucy Raymond, Anthony G Robson, Andrew R Webster, Gavin Arno, Fernanda Belga Ottoni Porto, Rui Chen

Faculty, Staff and Students Publications

PURPOSE: Previous studies suggest that ceramide is a proapoptotic lipid as high levels of ceramides can lead to apoptosis of neuronal cells, including photoreceptors. However, no pathogenic variant in ceramide synthases has been identified in human patients and knockout of various ceramide synthases in mice has not led to photoreceptor degeneration.

METHODS: Exome sequencing was used to identify candidate disease genes in patients with vision loss as confirmed by standard evaluation methods, including electroretinography (ERG) and optical coherence tomography. The vision loss phenotype in mice was evaluated by ERG and histological analyses.

RESULTS: Here we have identified four patients with …

Tbx5-Encoded T-Box Transcription Factor 5 Variant T223m Is Associated With Long Qt Syndrome And Pediatric Sudden Cardiac Death, Alexandra M Markunas, Perathu K R Manivannan, Jordan E Ezekian, Agnim Agarwal, William Eisner, Katherina Alsina, Hugh D Allen, Gregory A Wray, Jeffrey J Kim, Xander H T Wehrens, Andrew P Landstrom

Faculty, Staff and Students Publications

Long QT syndrome (LQTS) is a genetic disease resulting in a prolonged QT interval on a resting electrocardiogram, predisposing affected individuals to polymorphic ventricular tachycardia and sudden death. Although a number of genes have been implicated in this disease, nearly one in four individuals exhibiting the LQTS phenotype are genotype-negative. Whole-exome sequencing identified a missense T223M variant in TBX5 that cosegregates with prolonged QT interval in a family with otherwise genotype-negative LQTS and sudden death. The TBX5-T223M variant was absent among large ostensibly healthy populations (gnomAD) and predicted to be pathogenic by in silico modeling based on Panther, PolyPhen-2, Provean, …

Racial And Geographic Disparities In Influenza Vaccination In The Us Among Individuals With Atherosclerotic Cardiovascular Disease: Renewed Importance In The Setting Of Covid-19, Mahmoud Al Rifai, Umair Khalid, Arunima Misra, Jing Liu, Khurram Nasir, Miguel Cainzos-Achirica, Dhruv Mahtta, Christie M Ballantyne, Laura A Petersen, Salim S Virani

Faculty, Staff and Students Publications

INTRODUCTION: The importance of receiving an annual influenza vaccine among patients with atherosclerotic cardiovascular disease (ASCVD) is well established. With the rapid community spread and the possibility of another wave of COVID-19 infections in the fall, receiving an influenza vaccine is of particular importance to mitigate the risk associated with overlapping influenza and COVID-19 infections.

METHODS: We utilized cross-sectional data from the 2016 to 2019 Behavioral Risk Factor Surveillance System (BRFSS), a nationally representative U.S. telephone-based survey of adults 18 years or older. Race/ethnicity was our exposure of interest. We assessed the relative difference in influenza vaccination by race/ethnicity for …

Testosterone Therapy And Bone Quality In Men With Diabetes And Hypogonadism: Study Design And Protocol, Vittoria Russo, Georgia Colleluori, Rui Chen, Sanjay Mediwala, Clifford Qualls, Michael Liebschner, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

CONTEXT: Type 2 diabetes mellitus (T2D) is often accompanied by male hypogonadism and both conditions are associated with increased risk for fractures. Testosterone (T) has been shown to improve the bone health of hypogonadal men but has not been tested in patients who also have T2D in addition to low T. To date, there is no treatment that is specifically recommended for bone disease among patients with T2D. This study will evaluate the effect of T therapy on the bone health of male veterans with low T who also have T2D.

METHODS: This is a randomized double-blind placebo-controlled trial of …

Real World Clinicopathologic Observations Of Patients With Metastatic Solid Tumors Receiving Immune Checkpoint Inhibitor Therapy: Analysis From Kentucky Cancer Registry, Aasems Jacob, Jianrong Wu, Jill M. Kolesar, Eric B. Durbin, Aju Mathew, Susanne Arnold, Aman Chauhan

Biostatistics Faculty Publications

The state of Kentucky has the highest cancer incidence and mortality in the United States. High‐risk populations such as this are often underrepresented in clinical trials. The study aims to do a comprehensive analysis of molecular landscape of metastatic cancers among these patients with detailed evaluation of factors affecting response and outcomes to immune checkpoint inhibitor (ICI) therapy. We performed a retrospective analysis of metastatic solid tumor patients who received ICI and underwent molecular profiling at our institution.

Sixty nine patients with metastatic solid tumors who received ICI were included in the study. Prevalence of smoking and secondhand tobacco exposure …

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 Prospective Surveillance Study On The Kinetics Of The Humoral Immune Response To The Respiratory Syncytial Virus Fusion Protein In Adults In Houston, Texas, Brittani N Blunck, Letisha Aideyan, Xunyan Ye, Vasanthi Avadhanula, Laura Ferlic-Stark, Lynn Zechiedrich, Brian E Gilbert, Pedro A Piedra

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV)-specific serum antibody has been correlated to protection of infection and reduction of severe disease, but reinfection is still frequent. In this study, we evaluated RSV-specific serum antibody activity following natural RSV re-infection to examine the longevity of the humoral immune response in adults. Nineteen healthy adult volunteers under sixty-five years of age were enrolled during the 2018-2019 RSV season in Houston, TX. Blood was collected at three study visits. The kinetics of RSV-neutralizing, RSV F site-specific competitive, and RSV-binding antibodies in serum samples were measured by microneutralization and enzyme-linked immunosorbent assays. Three distinct profiles of RSV-specific …

Bone Microenvironmental Control Of Skeletal Malignancy, Chen Hao Lo

USF Tampa Graduate Theses and Dissertations

Bone is a common site of metastasis for many solid malignancies. Bone-metastatic cancers pose a significant clinical problem worldwide and is among the main causes for cancer patient morbidity and mortality. Patients with advanced bone-metastatic diseases often present with either osteolytic or osteogenic bone diseases as their cancers progress. These bone pathologies are products of the cancer co-opting the local bone remodeling stroma to yield important growth nutrients and factors. Unfortunately, skeletal metastases remain incurable and are fatal. Identifying and understanding the causal multicellular and molecular interactions underlying skeletal malignancies can yield crucial ideas for targeting and inhibiting disease progression. …

Continuous-Flow Left Ventricular Assist Device Therapy In Adults With Transposition Of The Great Vessels, Tadahisa Sugiura, Chitaru Kurihara, Masashi Kawabori, Andre C Critsinelis, Andrew B Civitello, Jeffrey A Morgan, O H Frazier

Faculty, Staff and Students Publications

An increasing number of children with congenital heart disease are surviving into adulthood and subsequently developing end-stage heart failure. Two example populations are adults who have been previously operated on for congenitally corrected transposition of the great arteries (CCTGA) and transposition of the great arteries (TGA). Implantation of a continuous flow left ventricular assist device (CF-LVAD) in these patients can present unusual anatomical and physiologic challenges. In this report, we describe outcomes of CF-LVAD implantation in three such patients. These cases demonstrate the feasibility of implanting a CF-LVAD in patients who have undergone surgery for CCTGA and/or TGA.

Kl-6 Levels In Covid-19, Giuliana Scarpati

Translational Medicine @ UniSa

We present preliminary results which encourage KL‐6 evaluation as a potential biomarker for phenotyping COVID-19 patients according to disease severity.

Neoadjuvant Anti-Ox40 (Medi6469) Therapy In Patients With Head And Neck Squamous Cell Carcinoma Activates And Expands Antigen-Specific Tumor-Infiltrating T Cells., Rebekka Duhen, Carmen Ballesteros-Merino, Alexandra K Frye, Eric Tran, Venkatesh Rajamanickam, Shu-Ching Chang, Yoshinobu Koguchi, Carlo Bifulco, Brady Bernard, Rom Leidner, Brendan Curti, Bernard A Fox, Walter Urba, Richard Bryan Bell, Andrew D Weinberg

Articles, Abstracts, and Reports

Despite the success of checkpoint blockade in some cancer patients, there is an unmet need to improve outcomes. Targeting alternative pathways, such as costimulatory molecules (e.g. OX40, GITR, and 4-1BB), can enhance T cell immunity in tumor-bearing hosts. Here we describe the results from a phase Ib clinical trial (NCT02274155) in which 17 patients with locally advanced head and neck squamous cell carcinoma (HNSCC) received a murine anti-human OX40 agonist antibody (MEDI6469) prior to definitive surgical resection. The primary endpoint was to determine safety and feasibility of the anti-OX40 neoadjuvant treatment. The secondary objective was to assess the effect of …

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 …

The Rac-Gef Tiam1 Promotes Dendrite And Synapse Stabilization Of Dentate Granule Cells And Restricts Hippocampal-Dependent Memory Functions, Jinxuan Cheng, Federico Scala, Francisco A Blanco, Sanyong Niu, Karen Firozi, Laura Keehan, Shalaka Mulherkar, Emmanouil Froudarakis, Lingyong Li, Joseph G Duman, Xiaolong Jiang, Kimberley F Tolias

Faculty, Staff and Students Publications

The dentate gyrus (DG) controls information flow into the hippocampus and is critical for learning, memory, pattern separation, and spatial coding, while DG dysfunction is associated with neuropsychiatric disorders. Despite its importance, the molecular mechanisms regulating DG neural circuit assembly and function remain unclear. Here, we identify the Rac-GEF Tiam1 as an important regulator of DG development and associated memory processes. In the hippocampus, Tiam1 is predominantly expressed in the DG throughout life. Global deletion of Tiam1 in male mice results in DG granule cells with simplified dendritic arbors, reduced dendritic spine density, and diminished excitatory synaptic transmission. Notably, DG …

Machine Intelligence Identifies Soluble Tnfa As A Therapeutic Target For Spinal Cord Injury, J. R. Huie, A. R. Ferguson, N. Kyritsis, J. Z. Pan, K.-A. Irvine, J. L. Nielson, P. G. Schupp, M. C. Oldham, John C. Gensel, A. Lin, M. R. Segal, R. R. Ratan, J. C. Bresnahan, M. S. Beattie

Spinal Cord and Brain Injury Research Center Faculty Publications

Traumatic spinal cord injury (SCI) produces a complex syndrome that is expressed across multiple endpoints ranging from molecular and cellular changes to functional behavioral deficits. Effective therapeutic strategies for CNS injury are therefore likely to manifest multi-factorial effects across a broad range of biological and functional outcome measures. Thus, multivariate analytic approaches are needed to capture the linkage between biological and neurobehavioral outcomes. Injury-induced neuroinflammation (NI) presents a particularly challenging therapeutic target, since NI is involved in both degeneration and repair. Here, we used big-data integration and large-scale analytics to examine a large dataset of preclinical efficacy tests combining five …

Association Of Nt-Probnp, Blood Pressure, And Cardiovascular Events: The Aric Study, Aliza Hussain, Wensheng Sun, Anita Deswal, James A De Lemos, John W Mcevoy, Ron C Hoogeveen, Kunihiro Matsushita, David Aguilar, Biykem Bozkurt, Salim S Virani, Amil M Shah, Elizabeth Selvin, Chiadi Ndumule, Christie M Ballantyne, Vijay Nambi

Faculty, Staff and Students Publications

BACKGROUND: Although intensive blood pressure reduction has cardiovascular benefits, the absolute benefit is greater in those at higher cardiovascular disease (CVD) risk.

OBJECTIVES: This study examined whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) helps identify subjects at higher risk for CVD events across systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse pressure (PP) categories.

METHODS: Participants from the ARIC (Atherosclerosis Risk In Communities) study visit 4 (1996 to 98) were grouped according to SBP, DBP, or PP categories and further stratified by NT-proBNP categories. Cox regression models were used to estimate hazard ratios for incident CVD (coronary heart disease, …

Dna Repair Pathways In Cancer Therapy And Resistance, Lan-Ya Li, Yi-Di Guan, Xi-Sha Chen, Jin-Ming Yang, Yan Cheng

Toxicology and Cancer Biology Faculty Publications

DNA repair pathways are triggered to maintain genetic stability and integrity when mammalian cells are exposed to endogenous or exogenous DNA-damaging agents. The deregulation of DNA repair pathways is associated with the initiation and progression of cancer. As the primary anti-cancer therapies, ionizing radiation and chemotherapeutic agents induce cell death by directly or indirectly causing DNA damage, dysregulation of the DNA damage response may contribute to hypersensitivity or resistance of cancer cells to genotoxic agents and targeting DNA repair pathway can increase the tumor sensitivity to cancer therapies. Therefore, targeting DNA repair pathways may be a potential therapeutic approach for …

Hermansky-Pudlak Syndrome-2 Alters Mitochondrial Homeostasis In The Alveolar Epithelium Of The Lung, Karina Cuevas-Mora, Willy Roque, Hoora Shaghaghi, Bernadette R Gochuico, Ivan O Rosas, Ross Summer, Freddy Romero

Faculty, Staff and Students Publications

BACKGROUND: Mitochondrial dysfunction has emerged as an important player in the pathogenesis of idiopathic pulmonary fibrosis (IPF), a common cause of idiopathic interstitial lung disease in adults. Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder that causes a similar type of pulmonary fibrosis in younger adults, although the role of mitochondrial dysfunction in this condition is not understood.

METHODS: We performed a detailed characterization of mitochondrial structure and function in lung tissues and alveolar epithelial cells deficient in the adaptor protein complex 3 beta 1 (Ap3b1) subunit, the gene responsible for causing subtype 2 of HPS (HPS-2).

RESULTS: We …