Medical Specialties Commons^™

Tcf7l2 Genetic Variants Do Not Influence Insulin Sensitivity Or Secretion Indices In Autoantibody-Positive Individuals At Risk For Type 1 Diabetes, Maria J Redondo, Megan V Warnock, Ingrid M Libman, Laura E Bocchino, David Cuthbertson, Susan Geyer, Alberto Pugliese, Andrea K Steck, Carmella Evans-Molina, Dorothy Becker, Jay M Sosenko, Fida Bacha, Type 1 Diabetes Trialnet Study Group

Children’s Nutrition Research Center Staff Publications

Objective: We aimed to test whether type 2 diabetes (T2D)-associated TCF7L2 genetic variants affect insulin sensitivity or secretion in autoantibody-positive relatives at risk for type 1 diabetes (T1D).

Research design and methods: We studied autoantibody-positive TrialNet Pathway to Prevention study participants (N = 1,061) (mean age 16.3 years) with TCF7L2 single nucleotide polymorphism (SNP) information and baseline oral glucose tolerance test (OGTT) to calculate indices of insulin sensitivity and secretion. With Bonferroni correction for multiple comparisons, P values < 0.0086 were considered statistically significant.

Results: None, one, and two T2D-linked TCF7L2 alleles were present in 48.1%, 43.9%, and 8.0% of the participants, respectively. Insulin sensitivity …

Exome Sequence Association Study Of Levels And Longitudinal Change Of Cardiovascular Risk Factor Phenotypes In European Americans And African Americans From The Atherosclerosis Risk In Communities Study, Elena V Feofanova, Elise Lim, Han Chen, Minjae Lee, Ching-Ti Liu, L Adrienne Cupples, Eric Boerwinkle

Faculty, Staff and Student Publications

Cardiovascular disease (CVD) is responsible for 31% of all deaths worldwide. Among CVD risk factors are age, race, increased systolic blood pressure (BP), and dyslipidemia. Both BP and blood lipids levels change with age, with a dose-dependent relationship between the cumulative exposure to hyperlipidemia and the risk of CVD. We performed an exome sequence association study using longitudinal data with up to 7805 European Americans (EAs) and 3171 African Americans (AAs) from the Atherosclerosis Risk in Communities (ARIC) study. We assessed associations of common (minor allele frequency > 5%) nonsynonymous and splice-site variants and gene-based sets of rare variants with levels …

Zfta-Rela Dictates Oncogenic Transcriptional Programs To Drive Aggressive Supratentorial Ependymoma, Amir Arabzade, Yanhua Zhao, Srinidhi Varadharajan, Hsiao-Chi Chen, Selin Jessa, Bryan Rivas, Austin J Stuckert, Minerva Solis, Alisha Kardian, Dana Tlais, Brian J Golbourn, Ann-Catherine J Stanton, Yuen San Chan, Calla Olson, Kristen L Karlin, Kathleen Kong, Robert Kupp, Baoli Hu, Sarah G Injac, Madeline Ngo, Peter R Wang, Luz A De León, Felix Sahm, Daisuke Kawauchi, Stefan M Pfister, Charles Y Lin, H Courtney Hodges, Irtisha Singh, Thomas F Westbrook, Murali M Chintagumpala, Susan M Blaney, Donald W Parsons, Kristian W Pajtler, Sameer Agnihotri, Richard J Gilbertson, Joanna Yi, Nada Jabado, Claudia L Kleinman, Kelsey C Bertrand, Benjamin Deneen, Stephen C Mack

Faculty, Staff and Students Publications

Over 60% of supratentorial (ST) ependymomas harbor a ZFTA-RELA (ZRfus) gene fusion (formerly C11orf95-RELA). To study the biology of ZRfus, we developed an autochthonous mouse tumor model using in utero electroporation (IUE) of the embryonic mouse brain. Integrative epigenomic and transcriptomic mapping was performed on IUE driven ZRfus tumors by CUT&RUN, ChIP, ATAC, and RNA sequencing and compared to human ZRfus driven ependymoma. In addition to direct canonical NF-κB pathway activation, ZRfus dictates a neoplastic transcriptional program and binds to thousands of unique sites across the genome that are enriched with Plagl family transcription factor (TF) motifs. ZRfus activates …

Structure And Dynamics Of Photoreceptor Sensory Cilia, Theodore G Wensel, Valencia L Potter, Abigail Moye, Zhixian Zhang, Michael A Robichaux

Faculty, Staff and Students Publications

The rod and cone photoreceptor cells of the vertebrate retina have highly specialized structures that enable them to carry out their function of light detection over a broad range of illumination intensities with optimized spatial and temporal resolution. Most prominent are their unusually large sensory cilia, consisting of outer segments packed with photosensitive disc membranes, a connecting cilium with many features reminiscent of the primary cilium transition zone, and a pair of centrioles forming a basal body which serves as the platform upon which the ciliary axoneme is assembled. These structures form a highway through which an enormous flux of …

Higher Entropy Observed In Sars-Cov-2 Genomes From The First Covid-19 Wave In Pakistan, Najia Karim Ghanchi, Asghar Nasir, Kiran I. Masood, Syed Hani Abidi, Syed Faisal Mahmood, Akber Kanji, Safina Abdul Razzak, Waqasuddin Khan, Saba Shahid, Maliha Yameen, Ali Raza, Javaria Ashraf, Zeeshan Ansar Ahmed, Mohammad Buksh Dharejo, Nazneen Islam, Zahra Hasan, Rumina Hasan

Department of Pathology and Laboratory Medicine

Background: We investigated the genome diversity of SARS-CoV-2 associated with the early COVID-19 period to investigate evolution of the virus in Pakistan.
Materials and methods: We studied ninety SARS-CoV-2 strains isolated between March and October 2020. Whole genome sequences from our laboratory and available genomes were used to investigate phylogeny, genetic variantion and mutation rates of SARS-CoV-2 strains in Pakistan. Site specific entropy analysis compared mutation rates between strains isolated before and after June 2020.
Results: In March, strains belonging to L, S, V and GH clades were observed but by October, only L and GH strains were present. The …

Balancing Science And Public Policy In Pakistan's Covid-19 Response, Zulfiqar Ahmed Bhutta, Faisal Sultan, Aamer Ikram, Adil H. Haider, Assad Hafeez, Muhammad Islam

Department of Paediatrics and Child Health

Background: Coronavirus disease 2019 (COVID-19) has affected the world in an unprecedented manner and South Asian countries were among the first to experience imported cases. Pakistan's response to COVID-19 has been under scrutiny for its granularity, reach and impact.
Aims: to evaluate objectively the chronology and depth of the response to COVID-19 in Pakistan.
Methods: We evaluated available national and subnational epidemiological and burden information on COVID-19 cases and deaths in Pakistan, including projection models available to the Government at an early stage of the pandemic.
Results: Pakistan, with a population of 215 million and considerable geographic diversity, experienced case …

Relationship Between Cognitive Performance And Lower Extremity Biomechanics: Implications For Sports-Related Concussion, Jason M. Avedesian, Tracey Covassin, Shelby Baez, Jennifer Nash, Ed Nagelhout, Janet S. Dufek

Physical Therapy Faculty Research

Background: Collegiate athletes with prior sports-related concussion (SRC) are at increased risk for lower extremity (LE) injuries; however, the biomechanical and cognitive mechanisms underlying the SRC-LE injury relationship are not well understood. Purpose: To examine the association between cognitive performance and LE land-and-cut biomechanics among collegiate athletes with and without a history of SRC and to determine the association among multiple cognitive testing batteries in the same athlete cohort. Study Design: Controlled laboratory study. Methods: A cohort of 20 collegiate athletes with prior SRC (9 men, 11 women; mean ± standard deviation [SD] age, 20.5 ± 1.3 years; mean ± …

Intravesical Cd74 And Cxcr4, Macrophage Migration Inhibitory Factor (Mif) Receptors, Mediate Bladder Pain, Shaojing Ye, Fei Ma, Dlovan F. D. Mahmood, Katherine L. Meyer-Siegler, Raymond E. Menard, David E. Hunt, Lin Leng, Richard Bucala, Pedro L. Vera

Physiology Faculty Publications

BACKGROUND: Activation of intravesical protease activated receptor 4 (PAR4) leads to release of urothelial macrophage migration inhibitory factor (MIF). MIF then binds to urothelial MIF receptors to release urothelial high mobility group box-1 (HMGB1) and elicit bladder hyperalgesia. Since MIF binds to multiple receptors, we investigated the contribution of individual urothelial MIF receptors to PAR4-induced HMGB1 release in vivo and in vitro and bladder pain in vivo.

METHODOLOGY/PRINCIPAL FINDINGS: We tested the effect of intravesical pre-treatment with individual MIF or MIF receptor (CD74, CXCR4, CXCR2) antagonists on PAR4-induced HMGB1 release in vivo (female C57/BL6 mice) and in vitro (primary …

A Novel Missense Mutation In Tnni3k Causes Recessively Inherited Cardiac Conduction Disease In A Consanguineous Pakistani Family, Shafaq Ramzan, Stephanie Tennstedt Stephanie Tennstedt, Muhammad Tariq, Sheraz Khan, Hafiza Noor Ul Ayan, Aamir Ali, Matthias Munz, Holger Thiele, Asad Aslam Korejo, Shahid Mahmood Baig

Department of Biological & Biomedical Sciences

Cardiac conduction disease (CCD), which causes altered electrical impulse propagation in the heart, is a life-threatening condition with high morbidity and mortality. It exhibits genetic and clinical heterogeneity with diverse pathomechanisms, but in most cases, it disrupts the synchronous activity of impulse-generating nodes and impulse-conduction underlying the normal heartbeat. In this study, we investigated a consanguineous Pakistani family comprised of four patients with CCD. We applied whole exome sequencing (WES) and co-segregation analysis, which identified a novel homozygous missense mutation (c.1531T>C;(p.Ser511Pro)) in the highly conserved kinase domain of the cardiac troponin I-interacting kinase (TNNI3K) encoding gene. The behaviors of …

Innate Immune Activation By Checkpoint Inhibition In Human Patient-Derived Lung Cancer Tissues, Teresa W. M. Fan, Richard M. Higashi, Huan Song, Saeed Daneshmandi, Angela L. Mahan, Matthew S. Purdom, Therese J. Bocklage, Thomas A. Pittman, Daheng He, Chi Wang, Andrew N. Lane

Center for Environmental and Systems Biochemistry Faculty Publications

Although Pembrolizumab-based immunotherapy has significantly improved lung cancer patient survival, many patients show variable efficacy and resistance development. A better understanding of the drug’s action is needed to improve patient outcomes. Functional heterogeneity of the tumor microenvironment (TME) is crucial to modulating drug resistance; understanding of individual patients’ TME that impacts drug response is hampered by lack of appropriate models. Lung organotypic tissue slice cultures (OTC) with patients’ native TME procured from primary and brain-metastasized (BM) non-small cell lung cancer (NSCLC) patients were treated with Pembrolizumab and/or beta-glucan (WGP, an innate immune activator). Metabolic tracing with ¹³C₆-Glc/ …

Discrepancy Between Pcr Based Sars-Cov-2 Tests Suggests The Need To Re-Evaluate Diagnostic Assays, Zain Mushtaq, Sadia Shakoor, Akber Kanji, Najma Shaheen, Asghar Nasir, Zeeshan Ansar Ahmed, Imran Ahmed, Syed Faisal Mahmood, Rumina Hasan, Zahra Hasan

Section of Internal Medicine

Objective: We investigated the discrepancy between clinical and PCR-based diagnosis of COVID-19. We compared results of ten patients with mild to severe COVID-19. Respiratory samples from all cases were tested on the Roche SARS-CoV-2 (Cobas) assay, Filmarray RP2.1 (bioMereiux) and TaqPath™ COVID19 (Thermofisher) PCR assays.
Results: Laboratory records of ten patients with mild to severe COVID-19 were examined. Initially, respiratory samples from the patients were tested as negative on the SARS-CoV-2 Roche® assay. Further investigation using the BIOFIRE® Filmarray RP2.1 assay identified SARS-CoV-2 as the pathogen in all ten cases. To investigate possible discrepancies between PCR assays, additional testing was …

Correcting For Sparsity And Interdependence In Glycomics By Accounting For Glycan Biosynthesis, Bokan Bao, Benjamin P Kellman, Austin W T Chiang, Yujie Zhang, James T Sorrentino, Austin K York, Mahmoud A Mohammad, Morey W Haymond, Lars Bode, Nathan E Lewis

Children’s Nutrition Research Center Staff Publications

Glycans are fundamental cellular building blocks, involved in many organismal functions. Advances in glycomics are elucidating the essential roles of glycans. Still, it remains challenging to properly analyze large glycomics datasets, since the abundance of each glycan is dependent on many other glycans that share many intermediate biosynthetic steps. Furthermore, the overlap of measured glycans can be low across samples. We address these challenges with GlyCompare, a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics, which enables direct comparison of different glycoprofiles and increases statistical power. …

Phylogenetic And Drug-Resistance Analysis Of Hiv-1 Sequences From An Extensive Paediatric Hiv-1 Outbreak In Larkana, Pakistan, Syed Hani Abidi, George Makau Nduva, Dilsha Siddiqui, Wardah Rafaqat, Syed Faisal Mahmood, Amna Rehana Siddiqui, Apsara Ali, Aneeta Hotwani, Rashida Abbas Ferrand, Fatima Mir

Department of Biological & Biomedical Sciences

Introduction: In April 2019, an HIV-1 outbreak among children occurred in Larkana, Pakistan, affecting more than a thousand children. It was assumed that the outbreak originated from a single source, namely a doctor at a private health facility. In this study, we performed subtype distribution, phylogenetic and drug-resistance analysis of HIV-1 sequences from 2019 outbreak in Larkana, Pakistan.
Methods: A total of 401 blood samples were collected between April-June 2019, from children infected with HIV-1 aged 0-15 years recruited into a case-control study to investigate the risk factors for HIV-1 transmission. Partial HIV-1 pol sequences were generated from 344 blood …

The Reel Deal: The Stacked Benefits Of A Reel Mower, John K. Hix, Simone Bailey

Advances in Clinical Medical Research and Healthcare Delivery

"Mow-lawning" is a colloquial term referred to actively cutting grass using a reel mower, typically at a faster than normal pace in order to maximize exercise benefit and minimize time, with the emphasis on the physical action of mowing and only secondarily on the resulting lawn care. While mow-lawning remains relatively uncommon in the United States, adoption of this practice by those healthy enough to engage in the level of exercise required can deliver a number of benefits that improve environmental, safety, and personal goals simultaneously. The stacking of so many benefits in one practice deserves more attention and promotion.

Dimensionality Reduction For Classification Of Object Weight From Electromyography, Elnaz Lashgari, Uri Maoz

Psychology Faculty Articles and Research

Electromyography (EMG) is a simple, non-invasive, and cost-effective technology for measuring muscle activity. However, multi-muscle EMG is also a noisy, complex, and high-dimensional signal. It has nevertheless been widely used in a host of human-machine-interface applications (electrical wheelchairs, virtual computer mice, prosthesis, robotic fingers, etc.) and, in particular, to measure the reach-and-grasp motions of the human hand. Here, we developed an automated pipeline to predict object weight in a reach-grasp-lift task from an open dataset, relying only on EMG data. In doing so, we shifted the focus from manual feature-engineering to automated feature-extraction by using pre-processed EMG signals and thus …

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …

Daily Energy Expenditure Through The Human Life Course, Herman Pontzer, Yosuke Yamada, Hiroyuki Sagayama, 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 Camps, Graeme L Close, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Lara R Dugas, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Annelies H Goris, Michael Gurven, Catherine Hambly, Asmaa El Hamdouchi, Marjije 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, Corby Martin, Anine C Medin, Erwin P Meijer, James C Morehen, James P Morton, Marian L Neuhouser, Teresa 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 Loechl, Amy H Luke, Jennifer Rood, Dale A Schoeller, Klaas R Westerterp, William W Wong, John R Speakman

Children’s Nutrition Research Center Staff Publications

Total daily energy expenditure (“total expenditure”, MJ/d) reflects daily energy needs and is a critical variable in human health and physiology, yet it is unclear how daily expenditure changes over the life course. Here, we analyze a large, globally diverse database of total expenditure measured by the doubly labeled water method for males and females aged 8 days to 95 yr. We show that total expenditure is strongly related to fat free mass in a power-law manner and identify four distinct metabolic life stages. Fat free mass-adjusted daily expenditure accelerates rapidly in neonates (0-1yr) to ~46% above adult values at …

Developing Methods To Detect And Diagnose Chronic Traumatic Encephalopathy During Life: Rationale, Design, And Methodology For The Diagnose Cte Research Project, Jeffrey Cummings, Numerous Authors, See Full List Below

School of Medicine Faculty Research

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been neuropathologically diagnosed in brain donors exposed to repetitive head impacts, including boxers and American football, soccer, ice hockey, and rugby players. CTE cannot yet be diagnosed during life. In December 2015, the National Institute of Neurological Disorders and Stroke awarded a seven-year grant (U01NS093334) to fund the “Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project.” The objectives of this multicenter project are to: develop in vivo fluid and neuroimaging biomarkers for CTE; characterize its clinical presentation; refine …

Associations Of Hair Dye And Relaxer Use With Breast Tumor Clinicopathologic Features: Findings From The Women’S Circle Of Health Study, Rohan Rao, Jasmine A. Mcdonald, Emily Barrett, Patricia Greenberg, Dede K. Teteh, Susanne B. Montgomery, Bo Qin, Yong Lin, Chi-Chen Hong, Christine B. Ambrosone, Kitaw Demissie, Elisa V. Bandera, Adana A.M. Llanos

Health Sciences and Kinesiology Faculty Articles

Background

Building upon our earlier findings of significant associations between hair dye and relaxer use with increased breast cancer risk, we evaluated associations of select characteristics of use with breast tumor clinicopathology.

Methods

Using multivariable-adjusted models we examined the associations of interest in a case-only study of 2998 women with breast cancer, overall and stratified by race and estrogen receptor (ER) status, addressing multiple comparisons using Bonferroni correction.

Results

Compared to salon application of permanent hair dye, home kit and combination application (both salon and home kit application) were associated with increased odds of poorly differentiated tumors in the overall …

Decoding The Roles Of Astrocytes And Hedgehog Signaling In Medulloblastoma, Terence Teixeira Duarte, Silvia Aparecida Teixeira, Luis Gonzalez-Reyes, Rui Manuel Reis

Publications and Research

The molecular evolution of medulloblastoma is more complex than previously imagined, as emerging evidence suggests that multiple interactions between the tumor cells and components of the tumor microenvironment (TME) are important for tumor promotion and progression. The identification of several molecular networks within the TME, which interact with tumoral cells, has provided new clues to understand the tumorigenic roles of many TME components as well as potential therapeutic targets. In this review, we discuss the most recent studies regarding the roles of astrocytes in supporting sonic hedgehog (SHH) subgroup medulloblastoma (MB) and provide an overview of MB progression through SHH …

Avoidant Restrictive Food Intake Disorder Prevalent Among Patients With Inflammatory Bowel Disease, Emily Yelencich, Emily Truong, Adrianne M. Widaman, Giselle Pignotti, Liu Yang, Yejoo Jeon, Andrew T. Weber, Rishabh Shah, Janelle Smith, Jenny S. Sauk, Berkeley N. Limketkai

Faculty Research, Scholarly, and Creative Activity

Background & Aims
Inflammatory bowel disease (IBD) patients alter their dietary behaviors to reduce disease-related symptoms, avoid feared food triggers, and control inflammation. This study aimed to estimate the prevalence of avoidant/restrictive food intake disorder (ARFID), evaluate risk factors, and examine the association with risk of malnutrition in patients with IBD.
Methods
This cross-sectional study recruited adult patients with IBD from an ambulatory clinic. ARFID risk was measured using the Nine-Item ARFID Screen. Nutritional risk was measured with the Patient Generated-Subjective Global Assessment. Logistic regression models were used to evaluate the association between clinical characteristics and a positive ARFID risk …

Pgc1Α Is Required For The Renoprotective Effect Of Lncrna Tug1 In Vivo And Links Tug1 With Urea Cycle Metabolites, Li Li, Jianyin Long, Koki Mise, Daniel L Galvan, Paul A Overbeek, Lin Tan, Shwetha V Kumar, Wai Kin Chan, Phillip L Lorenzi, Benny H Chang, Farhad R Danesh

Faculty, Staff and Students Publications

lncRNA taurine-upregulated gene 1 (Tug1) is a promising therapeutic target in the progression of diabetic nephropathy (DN), but the molecular basis of its protection remains poorly understood. Here, we generate a triple-mutant diabetic mouse model coupled with metabolomic profiling data to interrogate whether Tug1 interaction with peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) is required for mitochondrial remodeling and progression of DN in vivo. We find that, compared with diabetic conditional deletion of Pgc1α in podocytes alone (db/db; Pgc1αPod-f/f), diabetic Pgc1α knockout combined with podocyte-specific Tug1 overexpression (db/db; TugPodTg; Pgc1αPod-f/f) reverses the protective phenotype of …

Simple Energy Balance Or Microbiome For Childhood Obesity Prevention?, Tom Baranowski, Kathleen J Motil

Children’s Nutrition Research Center Staff Publications

Obesity prevention interventions generally have either not worked or had effects inadequate to mitigate the problem. They have been predicated on the simple energy balance model, which has been severely questioned by biological scientists. Numerous other etiological mechanisms have been proposed, including the intestinal microbiome, which has been related to childhood obesity in numerous ways. Public health research is needed in regard to diet and the microbiome, which hopefully will lead to effective child obesity prevention.

Monogenic Diabetes In Youth With Presumed Type 2 Diabetes: Results From The Progress In Diabetes Genetics In Youth (Prodigy) Collaboration, Jennifer N Todd, Jeffrey W Kleinberger, Haichen Zhang, Shylaja Srinivasan, Sherida E Tollefsen, Lynne L Levitsky, Lorraine E Levitt Katz, Jeanie B Tryggestad, Fida Bacha, Giuseppina Imperatore, Jean M Lawrence, Catherine Pihoker, Jasmin Divers, Jason Flannick, Dana Dabelea, Jose C Florez, Toni I Pollin

Children’s Nutrition Research Center Staff Publications

Objective: Maturity-onset diabetes of the young (MODY) is frequently misdiagnosed as type 1 or type 2 diabetes. Correct diagnosis may result in a change in clinical treatment and impacts prediction of complications and familial risk. In this study, we aimed to assess the prevalence of MODY in multiethnic youth under age 20 years with a clinical diagnosis of type 2 diabetes.

Research design and methods: We evaluated whole-exome sequence data of youth with a clinical diagnosis of type 2 diabetes. We considered participants to have MODY if they carried a MODY gene variant classified as likely pathogenic (LP) or pathogenic …

A Noncoding Rna Modulator Potentiates Phenylalanine Metabolism In Mice, Yajuan Li, Zhi Tan, Yaohua Zhang, Zhao Zhang, Qingsong Hu, Ke Liang, Yao Jun, Youqiong Ye, Yi-Chuan Li, Chunlai Li, Lan Liao, Jianming Xu, Zhen Xing, Yinghong Pan, Sujash S Chatterjee, Tina K Nguyen, Heidi Hsiao, Sergey D Egranov, Nagireddy Putluri, Cristian Coarfa, David H Hawke, Preethi H Gunaratne, Kuang-Lei Tsai, Leng Han, Mien-Chie Hung, George A Calin, Fares Namour, Jean-Louis Guéant, Ania C Muntau, Nenad Blau, V Reid Sutton, Manuel Schiff, François Feillet, Shuxing Zhang, Chunru Lin, Liuqing Yang

Faculty, Staff and Students Publications

The functional role of long noncoding RNAs (lncRNAs) in inherited metabolic disorders, including phenylketonuria (PKU), is unknown. We demonstrated that the mouse lncRNA Pair and human HULC associate with phenylalanine hydroxylase (PAH). Pair-knockout mice exhibited excessive blood phenylalanine, musty odor, hypopigmentation, growth retardation, and progressive neurological symptoms including seizures, which faithfully models human PKU. HULC depletion led to reduced PAH enzymatic activities in human induced pluripotent stem cell (hiPSC)-differentiated hepatocytes. Mechanistically, HULC modulated the enzymatic activities of PAH by facilitating PAH-substrate and PAH-cofactor interactions. To develop a therapeutic strategy for restoring liver lncRNAs, we designed GalNAc-tagged lncRNA mimics that …

Comparison Of Constant Load Exercise Intensity For Verification Of Maximal Oxygen Uptake Following A Graded Exercise Test In Older Adults, Ian R. Villanueva, John C. Campbell, Serena M. Medina, Theresa M. Jorgensen, Shannon L. Wilson, Siddhartha S. Angadi, Glenn A. Gaesser, Jared M. Dickinson

All Faculty Scholarship for the College of Education and Professional Studies

Maximal oxygen uptake (VO₂max) declines with advancing age and is a predictor of morbidity and mortality risk. The purpose here was to assess the utility of constant load tests performed either above or below peak work rate obtained from a graded exercise test for verification of VO₂max in older adults. Twenty-two healthy older adults (9M, 13F, 67 ± 6 years, BMI: 26.3 ± 5.1 kg·m⁻²) participated in the study. Participants were asked to complete two experimental trials in a randomized, counterbalanced cross-over design. Both trials (cycle ergometer) consisted of (1) an identical graded exercise …

Family-Based Obesity Prevention Interventions Among Hispanic Children And Families: A Scoping Review, Erica G Soltero, Armando Peña, Veronica Gonzalez, Edith Hernandez, Guisela Mackey, Chishinga Callender, Jayna M Dave, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

This scoping review examined intervention and sample characteristics of family-based obesity prevention interventions among Hispanic youth. This review also examined the degree to which existing interventions were culturally-adapted, acknowledged social determinants of health (SDoH), and collaborated with community stakeholders. A comprehensive search across Medline Ovid, Embase, Scopus, PsycInfo, and Pubmed was used to identify 13 studies primarily based in the U.S. (92.3%). Data was extracted by two independent reviewers. Most used a randomized control trial design (69.2%), a behavior change theory (84.6%), and reported moderate to high (≥70%) retention (69.2%). Studies targeted improvements in physical activity (69.2%) and fruit and …

A Machine Learning Case-Control Classifier For Schizophrenia Based On Dna Methylation In Blood, Chathura J Gunasekara, Eilis Hannon, Harry Mackay, Cristian Coarfa, Andrew Mcquillin, David St Clair, Jonathan Mill, Robert A Waterland

Children’s Nutrition Research Center Staff Publications

Epigenetic dysregulation is thought to contribute to the etiology of schizophrenia (SZ), but the cell type-specificity of DNA methylation makes population-based epigenetic studies of SZ challenging. To train an SZ case–control classifier based on DNA methylation in blood, therefore, we focused on human genomic regions of systemic interindividual epigenetic variation (CoRSIVs), a subset of which are represented on the Illumina Human Methylation 450K (HM450) array. HM450 DNA methylation data on whole blood of 414 SZ cases and 433 non-psychiatric controls were used as training data for a classification algorithm with built-in feature selection, sparse partial least squares discriminate analysis (SPLS-DA); …

Rsv-Induced Guillain–Barré Syndrome, Priyanga Jayakumar, Christe Shen, Dylan Goldsmith, Steven Lippmann

The University of Louisville Journal of Respiratory Infections

A patient with respiratory syncytial virus-induced Guillain–Barré Syndrome and acute disseminated encephalomyelitis is presented. This virus is the most common cause of upper respiratory infections, and it can become an etiology for extra-pulmonary pathology with serious complications. Such a case is rare, but the possibility of adverse comorbidities makes early diagnosis and treatment important.

Biomarkers For Impending Risk Of Osteoporosis In Premenopausal Women, Rehana Rehman, Ali Usman, Aisha Sheikh, Rozeena Baig

Department of Biological & Biomedical Sciences

Objective: To compare 'cytokines' and 'bone turnover markers' in pre- and post-menopausal women and identify their relationship with bone mineral density (BMD) in both groups. Study Design: A cross-sectional study.
Place and duration of study: Department of Biological & Biomedical Sciences, The Aga Khan University, Karachi, Pakistan, from June 2017 to August 2019.
Methodology: Groups comprised of healthy premenopausal and postmenopausal women from the general population belonging to different ethnic groups and socio-economic status. Serum cytokines and bone turnover markers were assessed by solid-phase immunoassays, BMD (gm /cm2)] measurement was performed by dual-energy X-ray absorptiometry at the hip, lumbar spine, …