Life Sciences Commons^™

Physical Activity And Fat-Free Mass During Growth And In Later Life, Klaas R Westerterp, 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 J A Camps, Graeme L Close, Jamie A Cooper, Sai K Das, Richard Cooper, Lara R Dugas, 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, 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, Amy H Luke, Herman Pontzer, Jennifer Rood, Dale A Schoeller, William W Wong, John R Speakman

Children’s Nutrition Research Center Staff Publications

BACKGROUND: Physical activity may be a way to increase and maintain fat-free mass (FFM) in later life, similar to the prevention of fractures by increasing peak bone mass.

OBJECTIVES: A study is presented of the association between FFM and physical activity in relation to age.

METHODS: In a cross-sectional study, FFM was analyzed in relation to physical activity in a large participant group as compiled in the International Atomic Energy Agency Doubly Labeled Water database. The database included 2000 participants, age 3-96 y, with measurements of total energy expenditure (TEE) and resting energy expenditure (REE) to allow calculation of physical …

Indoxyl Sulfate, A Gut Microbiome-Derived Uremic Toxin, Is Associated With Psychic Anxiety And Its Functional Magnetic Resonance Imaging-Based Neurologic Signature, Christopher R. Brydges, Oliver Fiehn, Helen S. Mayberg, Henry Schreiber, Siamak Mahmoudian Dehkordi, Sudeepa Bhattacharyya, Jungho Cha, Ki Sueng Choi, W Edward Craighead, Ranga R. Krishnan, A John Rush, Boadie W. Dunlop, Rima Kaddurah-Daouk

Arkansas Biosciences Institute

It is unknown whether indoles, metabolites of tryptophan that are derived entirely from bacterial metabolism in the gut, are associated with symptoms of depression and anxiety. Serum samples (baseline, 12 weeks) were drawn from participants (n = 196) randomized to treatment with cognitive behavioral therapy (CBT), escitalopram, or duloxetine for major depressive disorder. Baseline indoxyl sulfate abundance was positively correlated with severity of psychic anxiety and total anxiety and with resting state functional connectivity to a network that processes aversive stimuli (which includes the subcallosal cingulate cortex (SCC-FC), bilateral anterior insula, right anterior midcingulate cortex, and the right premotor areas). …

Comprehensive Characterization Of Covid-19 Patients With Repeatedly Positive Sars-Cov-2 Tests Using A Large Us Electronic Health Record Database, Xiao Dong, Yujia Zhou, Xiao-Ou Shu, Elmer V Bernstam, Rebecca Stern, David M Aronoff, Hua Xu, Loren Lipworth

Faculty, Staff and Student Publications

In the absence of genome sequencing, two positive molecular tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) separated by negative tests, prolonged time, and symptom resolution remain the best surrogate measure of possible reinfection. Using a large electronic health record database, we characterized clinical and testing data for 23 patients with repeatedly positive SARS-CoV-2 PCR test results ≥60 days apart, separated by ≥2 consecutive negative test results. The prevalence of chronic medical conditions, symptoms, and severe outcomes related to coronavirus disease 19 (COVID-19) illness were ascertained. The median age of patients was 64.5 years, 40% were Black, and 39% …

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 …

Blood N-3 Fatty Acid Levels And Total And Cause-Specific Mortality From 17 Prospective Studies, William S Harris, Nathan L Tintle, Fumiaki Imamura, Frank Qian, Andres V Ardisson Korat, Matti Marklund, Luc Djoussé, Julie K Bassett, Pierre-Hugues Carmichael, Yun-Yu Chen, Yoichiro Hirakawa, Leanne K Küpers, Federica Laguzzi, Maria Lankinen, Rachel A Murphy, Cécilia Samieri, Mackenzie K Senn, Peilin Shi, Jyrki K Virtanen, Ingeborg A Brouwer, Kuo-Liong Chien, Gudny Eiriksdottir, Nita G Forouhi, Johanna M Geleijnse, Graham G Giles, Vilmundur Gudnason, Catherine Helmer, Allison Hodge, Rebecca Jackson, Kay-Tee Khaw, Markku Laakso, Heidi Lai, Danielle Laurin, Karin Leander, Joan Lindsay, Renata Micha, Jaako Mursu, Toshiharu Ninomiya, Wendy Post, Bruce M Psaty, Ulf Risérus, Jennifer G Robinson, Aladdin H Shadyab, Linda Snetselaar, Aleix Sala-Vila, Yangbo Sun, Lyn M Steffen, Michael Y Tsai, Nicholas J Wareham, Alexis C Wood, Jason H Y Wu, Frank Hu, Qi Sun, David S Siscovick, Rozenn N Lemaitre, Dariush Mozaffarian, Fatty Acids And Outcomes Research Consortium (Force)

Children’s Nutrition Research Center Staff Publications

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.

Genetic And Non-Genetic Factors Affecting The Expression Of Covid-19-Relevant Genes In The Large Airway Epithelium, Silva Kasela, Victor E Ortega, Molly Martorella, Suresh Garudadri, Jenna Nguyen, Elizabeth Ampleford, Anu Pasanen, Srilaxmi Nerella, Kristina L Buschur, Igor Z Barjaktarevic, R Graham Barr, Eugene R Bleecker, Russell P Bowler, Alejandro P Comellas, Christopher B Cooper, David J Couper, Gerard J Criner, Jeffrey L Curtis, Meilan K Han, Nadia N Hansel, Eric A Hoffman, Robert J Kaner, Jerry A Krishnan, Fernando J Martinez, Merry-Lynn N Mcdonald, Deborah A Meyers, Robert Paine, Stephen P Peters, Mario Castro, Loren C Denlinger, Serpil C Erzurum, John V Fahy, Elliot Israel, Nizar N Jarjour, Bruce D Levy, Xingnan Li, Wendy C Moore, Sally E Wenzel, Charles Langelier, Prescott G Woodruff, Tuuli Lappalainen, Stephanie A Christenson

Faculty, Staff and Student Publications

BACKGROUND: The large airway epithelial barrier provides one of the first lines of defense against respiratory viruses, including SARS-CoV-2 that causes COVID-19. Substantial inter-individual variability in individual disease courses is hypothesized to be partially mediated by the differential regulation of the genes that interact with the SARS-CoV-2 virus or are involved in the subsequent host response. Here, we comprehensively investigated non-genetic and genetic factors influencing COVID-19-relevant bronchial epithelial gene expression.

METHODS: We analyzed RNA-sequencing data from bronchial epithelial brushings obtained from uninfected individuals. We related ACE2 gene expression to host and environmental factors in the SPIROMICS cohort of smokers with …

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

The Circadian Cryptochrome, Cry1, Is A Pro-Tumorigenic Factor That Rhythmically Modulates Dna Repair., Ayesha A Shafi, Chris M Mcnair, Jennifer J Mccann, Mohammed Alshalalfa, Anton Shostak, Tesa M Severson, Yanyun Zhu, Andre Bergman, Nicolas Gordon, Amy C Mandigo, Saswati N Chand, Peter Gallagher, Emanuela Dylgjeri, Talya S Laufer, Irina A Vasilevskaya, Matthew J Schiewer, Michael Brunner, Felix Y Feng, Wilbert Zwart, Karen E Knudsen

Department of Cancer Biology Faculty Papers

Mechanisms regulating DNA repair processes remain incompletely defined. Here, the circadian factor CRY1, an evolutionally conserved transcriptional coregulator, is identified as a tumor specific regulator of DNA repair. Key findings demonstrate that CRY1 expression is androgen-responsive and associates with poor outcome in prostate cancer. Functional studies and first-in-field mapping of the CRY1 cistrome and transcriptome reveal that CRY1 regulates DNA repair and the G2/M transition. DNA damage stabilizes CRY1 in cancer (in vitro, in vivo, and human tumors ex vivo), which proves critical for efficient DNA repair. Further mechanistic investigation shows that stabilized CRY1 temporally regulates expression of genes required …

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 …

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 …

A Genome-Wide Association Study Discovers 46 Loci Of The Human Metabolome In The Hispanic Community Health Study/Study Of Latinos, Elena V Feofanova, Han Chen, Yulin Dai, Peilin Jia, Megan L Grove, Alanna C Morrison, Qibin Qi, Martha Daviglus, Jianwen Cai, Kari E North, Cathy C Laurie, Robert C Kaplan, Eric Boerwinkle, Bing Yu

Faculty, Staff and Student Publications

Variation in levels of the human metabolome reflect changes in homeostasis, providing a window into health and disease. The genetic impact on circulating metabolites in Hispanics, a population with high cardiometabolic disease burden, is largely unknown. We conducted genome-wide association analyses on 640 circulating metabolites in 3,926 Hispanic Community Health Study/Study of Latinos participants. The estimated heritability for 640 metabolites ranged between 0%-54% with a median at 2.5%. We discovered 46 variant-metabolite pairs (p value < 1.2 × 10

Health And Disease Markers Correlate With Gut Microbiome Composition Across Thousands Of People., Ohad Manor, Chengzhen L Dai, Sergey A Kornilov, Brett Smith, Nathan D Price, Jennifer C Lovejoy, Sean M Gibbons, Andrew T Magis

Articles, Abstracts, and Reports

Variation in the human gut microbiome can reflect host lifestyle and behaviors and influence disease biomarker levels in the blood. Understanding the relationships between gut microbes and host phenotypes are critical for understanding wellness and disease. Here, we examine associations between the gut microbiota and ~150 host phenotypic features across ~3,400 individuals. We identify major axes of taxonomic variance in the gut and a putative diversity maximum along the Firmicutes-to-Bacteroidetes axis. Our analyses reveal both known and unknown associations between microbiome composition and host clinical markers and lifestyle factors, including host-microbe associations that are composition-specific. These results suggest potential opportunities …

Representation Of Ehr Data For Predictive Modeling: A Comparison Between Umls And Other Terminologies, Laila Rasmy, Firat Tiryaki, Yujia Zhou, Yang Xiang, Cui Tao, Hua Xu, Degui Zhi

Faculty, Staff and Student Publications

OBJECTIVE: Predictive disease modeling using electronic health record data is a growing field. Although clinical data in their raw form can be used directly for predictive modeling, it is a common practice to map data to standard terminologies to facilitate data aggregation and reuse. There is, however, a lack of systematic investigation of how different representations could affect the performance of predictive models, especially in the context of machine learning and deep learning.

MATERIALS AND METHODS: We projected the input diagnoses data in the Cerner HealthFacts database to Unified Medical Language System (UMLS) and 5 other terminologies, including CCS, CCSR, …

Genetic Variant Effects On Gene Expression In Human Pancreatic Islets And Their Implications For T2d., Ana Viñuela, Arushi Varshney, Martijn Van De Bunt, Rashmi B Prasad, Olof Asplund, Amanda Bennett, Michael Boehnke, Andrew A Brown, Michael R Erdos, João Fadista, Ola Hansson, Gad Hatem, Cédric Howald, Apoorva K Iyengar, Paul Johnson, Ulrika Krus, Patrick E Macdonald, Anubha Mahajan, Jocelyn E Manning Fox, Narisu Narisu, Vibe Nylander, Peter Orchard, Nikolay Oskolkov, Nikolaos I Panousis, Anthony Payne, Michael L. Stitzel, Swarooparani Vadlamudi, Ryan Welch, Francis S Collins, Karen L Mohlke, Anna L Gloyn, Laura J Scott, Emmanouil T Dermitzakis, Leif Groop, Stephen C J Parker, Mark I Mccarthy

Faculty Research 2020

Most signals detected by genome-wide association studies map to non-coding sequence and their tissue-specific effects influence transcriptional regulation. However, key tissues and cell-types required for functional inference are absent from large-scale resources. Here we explore the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using data from 420 donors. We find: (a) 7741 cis-eQTLs in islets with a replication rate across 44 GTEx tissues between 40% and 73%; (b) marked overlap between islet cis-eQTL signals and active regulatory sequences in islets, with reduced eQTL effect size observed in …

Prevalence And Factors Associated With Overweight And Central Obesity Among Adults In The Eastern Sudan, Saeed M. Omar, Zainab Taha, Ahmed Ali Hassan, Osama Al-Wutayd, Ishag Adam

All Works

© 2020 Omar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background A global epidemic of obesity has been documented, particularly among African countries. While central obesity and overweight have been reported for many countries, very limited information exists about the prevalence of these health problems in Sudan, and these data are nonexistent for Eastern Sudan. The present study aimed to determine the prevalence of obesity and central obesity, as well as …

Evidence For Gene-Smoking Interactions For Hearing Loss And Deafness In Japanese American Families, Jia Y Wan, Christina Cataby, Andrew Liem, Emily Jeffrey, Trina M Norden-Krichmar, Deborah Goodman, Stephanie A Santorico, Karen L Edwards

Faculty, Staff and Student Publications

BACKGROUND: This study investigated the relationship between smoking and hearing loss and deafness (HLD) and whether the relationship is modified by genetic variation. Data for these analyses was from the subset of Japanese American families collected as part of the American Diabetes Association Genetics of Non-insulin Dependent Diabetes Mellitus study. Logistic regression with generalized estimating equations assessed the relationship between HLD and smoking. Nonparametric linkage analysis identified genetic regions harboring HLD susceptibility genes and ordered subset analysis was used to identify regions showing evidence for gene-smoking interactions. Genetic variants within these candidate regions were then each tested for interaction with …

Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito

Physiology Faculty Publications

Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of …

The Gut-Microbiome In Gulf War Veterans: A Preliminary Report, Patricia A. Janulewicz, Ratanesh K. Seth, Jeffrey M. Carlson, Joy Ajama, Emily Quinn, Timothy Heeren, Nancy Klimas, Steven M. Lasley, Ronnie Horner, Kimberly Sullivan, Saurabh Chatterjee

Faculty Publications

Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting the central nervous system (CNS), immune and gastrointestinal (GI) systems of Gulf War veterans (GWV). We assessed the relationships between GWI, GI symptoms, gut microbiome and inflammatory markers in GWV from the Boston Gulf War Illness Consortium (GWIC). Three groups of GWIC veterans were recruited in this pilot study; GWV without GWI and no gastrointestinal symptoms (controls), GWV with GWI and no gastrointestinal symptoms (GWI-GI), GWV with GWI who reported gastrointestinal symptoms (GW+GI). Here we report on a subset of the first thirteen stool samples analyzed. Results showed significantly different …

Effects Of 6 Months Of Exercise-Based Cardiac Rehabilitation On Autonomic Function And Neuro-Cardiovascular Stress Reactivity In Coronary Artery Disease Patients., Mark B Badrov, Katelyn N Wood, Sophie Lalande, Carolyn P Sawicki, Lindsay J Borrell, Carly C Barron, Jennifer L Vording, Arlene Fleischhauer, Neville Suskin, Cheri L Mcgowan, J Kevin Shoemaker

Kinesiology Publications

Background Autonomic dysregulation represents a hallmark of coronary artery disease (CAD). Therefore, we investigated the effects of exercise-based cardiac rehabilitation (CR) on autonomic function and neuro-cardiovascular stress reactivity in CAD patients. Methods and Results Twenty-two CAD patients (4 women; 62±8 years) were studied before and following 6 months of aerobic- and resistance-training-based CR. Twenty-two similarly aged, healthy individuals (CTRL; 7 women; 62±11 years) served as controls. We measured blood pressure, muscle sympathetic nerve activity, heart rate, heart rate variability (linear and nonlinear), and cardiovagal (sequence method) and sympathetic (linear relationship between burst incidence and diastolic blood pressure) baroreflex sensitivity during …

An Integrative Cross-Omics Analysis Of Dna Methylation Sites Of Glucose And Insulin Homeostasis, Jun Liu, Elena Carnero-Montoro, Jenny Van Dongen, Samantha Lent, Ivana Nedeljkovic, Symen Ligthart, Pei-Chien Tsai, Tiphaine C. Martin, Pooja R. Mandaviya, Rick Jansen, Marjolein J. Peters, Liesbeth Duijts, Vincent W. V. Jaddoe, Henning Tiemeier, Janine F. Felix, Gonneke Willemsen, Eco J. C. De Geus, Audrey Y. Chu, Daniel Levy, Shih-Jen Hwang, Jan Bressler, Rahul Gondalia, Elias L. Salfati, Christian Herder, Bertha A. Hidalgo, Toshiko Tanaka, Ann Zenobia Moore, Rozenn N. Lemaitre, Min A. Jhun, Jennifer A. Smith, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation …

Developmental Expression Of The Cytosolic Sulfotransferases In Human Liver., Sarah Dubaisi, Joseph A. Caruso, R Gaedigk, Carrie A. Vyhlidal, Philip C. Smith, Ronald N. Hines, Thomas A. Kocarek, Melissa Runge-Morris

Manuscripts, Articles, Book Chapters and Other Papers

The liver is the predominant organ of metabolism for many endogenous and foreign chemicals. Cytosolic sulfotransferases (SULTs) catalyze the sulfonation of drugs and other xenobiotics, as well as hormones, neurotransmitters, and sterols, with consequences that include enhanced drug elimination, hormone inactivation, and procarcinogen bioactivation. SULTs are classified into six gene families, but only SULT1 and SULT2 enzymes are expressed in human liver. We characterized the developmental expression patterns of SULT1 and SULT2 mRNAs and proteins in human liver samples using reverse transcription quantitative polymerase chain reaction (RT-qPCR), RNA sequencing, and targeted quantitative proteomics. Using a set of prenatal, infant, and …

Buparlisib In Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase Ii Trial., Patrick Y Wen, Mehdi Touat, Brian M Alexander, Ingo K Mellinghoff, Shakti Ramkissoon, Christine S Mccluskey, Kristine Pelton, Sam Haidar, Sankha S Basu, Sarah C Gaffey, Loreal E Brown, Juan Emmanuel Martinez-Ledesma, Shaofang Wu, Jungwoo Kim, Wei Wei, Mi-Ae Park, Jason T Huse, John G Kuhn, Mikael L Rinne, Howard Colman, Nathalie Y R Agar, Antonio M Omuro, Lisa M Deangelis, Mark R Gilbert, John F De Groot, Timothy F Cloughesy, Andrew S Chi, Thomas M Roberts, Jean J Zhao, Eudocia Q Lee, Lakshmi Nayak, James R Heath, Laura L Horky, Tracy T Batchelor, Rameen Beroukhim, Susan M Chang, Azra H Ligon, Ian F Dunn, Dimpy Koul, Geoffrey S Young, Michael D Prados, David A Reardon, W K Alfred Yung, Keith L Ligon

Articles, Abstracts, and Reports

PURPOSE: Phosphatidylinositol 3-kinase (PI3K) signaling is highly active in glioblastomas. We assessed pharmacokinetics, pharmacodynamics, and efficacy of the pan-PI3K inhibitor buparlisib in patients with recurrent glioblastoma with PI3K pathway activation.

METHODS: This study was a multicenter, open-label, multi-arm, phase II trial in patients with PI3K pathway-activated glioblastoma at first or second recurrence. In cohort 1, patients scheduled for re-operation after progression received buparlisib for 7 to 13 days before surgery to evaluate brain penetration and modulation of the PI3K pathway in resected tumor tissue. In cohort 2, patients not eligible for re-operation received buparlisib until progression or unacceptable toxicity. Once …

Saturated Fatty Acid Activates T Cell Inflammation Through A Nicotinamide Nucleotide Transhydrogenase (Nnt)-Dependent Mechanism, Grace Mccambridge, Madhur Agrawal, Alanna Keady, Philip A. Kern, Hatice Hasturk, Barbara S. Nikolajczyk, Leena P. Bharath

Pharmacology and Nutritional Sciences Faculty Publications

Circulating fatty acids (FAs) increase with obesity and can drive mitochondrial damage and inflammation. Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial protein that positively regulates nicotinamide adenine dinucleotide phosphate (NADPH), a key mediator of energy transduction and redox homeostasis. The role that NNT-regulated bioenergetics play in the inflammatory response of immune cells in obesity is untested. Our objective was to determine how free fatty acids (FFAs) regulate inflammation through impacts on mitochondria and redox homeostasis of peripheral blood mononuclear cells (PBMCs). PBMCs from lean subjects were activated with a T cell-specific stimulus in the presence or absence of generally pro-inflammatory …

Association Between Spatial Access To Food Outlets, Frequency Of Grocery Shopping, And Objectively-Assessed And Self-Reported Fruit And Vegetable Consumption, Jared T. Mcguirt, Stephanie B. Jilcott Pitts, Alison Gustafson

Dietetics and Human Nutrition Faculty Publications

Because supermarkets are a critical part of the community food environment, the purpose of this paper is to examine the association between accessibility to the supermarket where participants were surveyed, frequency of shopping at the supermarket, and self-reported and objectively-assessed fruit and vegetable consumption. Accessibility was assessed using Geographic Information Systems (GIS) measured distance and multiple versions of the modified Retail Food Environment Index (mRFEI), including a localized road network buffer version. Frequency of shopping was assessed using self-report. The National Cancer Institute Fruit and Vegetable screener was used to calculate daily servings of fruits and vegetables. Skin carotenoids were …

Cross-Sectional And Longitudinal Association Between Glycemic Status And Body Composition In Men: A Population-Based Study, Khaleal Almusaylim, Maggie Minett, Teresa L. Binkley, Tianna M. Beare, Bonny Specker

Ethel Austin Martin Program Publications

This study sought to evaluate the associations between changes in glycemic status and changes in total body (TB), trunk, and appendicular fat (FM) and lean mass (LM) in men. A population-based study of men aged 20–66 years at baseline were included in cross-sectional (n = 430) and three-year longitudinal (n = 411) analyses. Prediabetes was defined as fasting glucose 100–125 mg/dL. Type 2 diabetes (T2D) was determined by: self-reported diabetes, current anti-diabetic drug use (insulin/oral hypoglycemic agents), fasting glucose (≥126 mg/dL), or non-fasting glucose (≥200 mg/dL). Body composition was evaluated by dual-energy X-ray absorptiometry. Longitudinal analyses showed that changes in …

Survival Of Patients With Subglottic Squamous Cell Carcinoma, S D. Macneil, K Patel, K Liu, S Shariff, J Yoo, A Nichols, K Fung, A X Garg

Anatomy and Cell Biology Publications

Objective: Subglottic squamous cell carcinoma is a rare subsite of laryngeal cancer that behaves more aggressively and portends a worse prognosis. Using a population-based cancer registry, our objective was to report overall survival (OS) and laryngectomy-free survival (LFS) in patients diagnosed with subglottic squamous cell carcinoma, and to determine whether primary laryngectomy results in improved survival.

Methods: This retrospective population-based study considered patients with a new diagnosis of squamous cell carcinoma in the province of Ontario over a 15-year period (1995-2009). The Ontario Cancer Registry was examined for patients with the diagnosis of interest during the period …

Effects Of A Community Population Health Initiative On Blood Pressure Control In Latinos, James R Langabeer, Timothy D Henry, Carlos Perez Aldana, Larissa Deluna, Nora Silva, Tiffany Champagne-Langabeer

Faculty, Staff and Student Publications

Background Hypertension remains one of the most important, modifiable cardiovascular risk factors. Yet, the largest minority ethnic group (Hispanics/Latinos) often have different health outcomes and behavior, making hypertension management more difficult. We explored the effects of an American Heart Association-sponsored population health intervention aimed at modifying behavior of Latinos living in Texas. Methods and Results We enrolled 8071 patients, and 5714 (65.7%) completed the 90-day program (58.5 years ±11.7; 59% female) from July 2016 to June 2018. Navigators identified patients with risk factors; initial and final blood pressure ( BP ) readings were performed in the physician's office; and interim …

Differences In Physical Activity And Diet Patterns Between Non-Rural And Rural Adults., Lacey Mccormack, Howard Wey, Jessica R. Meendering, Bonny Specker

Health and Nutritional Sciences Faculty Publications

BACKGROUND: It is unclear how rural occupations and lifestyles may play a role in shaping physical activity and diet behaviors that contribute to the rural⁻urban obesity disparity.
METHODS: Data come from the prospective and observational South Dakota Rural Bone Health Study, which included adults aged 20⁻66 years in three groups: (1) non-rural non-Hutterite, (2) rural non-Hutterite, and (3) rural Hutterite. Physical activity data were collected using 7-day physical activity questionnaires, and hours per day in physical activity categories are reported. Diet data were collected using food frequency questionnaires, and food group servings per day (svg/day) are reported. Mixed models were …

Rationale, Design And Methods Of "Set The Rules": A Tailored Peer-To-Peer Health Information Intervention, Jennifer R. Warren, Brandi M. White

Health and Clinical Sciences Faculty Publications

Ensuring equitable access to health information is one strategy to promote health equity for underserved communities, especially for low-income African Americans (AAs). Childcare centers are one viable site to deliver health information to address this disparity. This paper describes the methods used in a community-based participatory research project with a childcare facility that aimed to reduce environmental tobacco smoke (ETS) exposure among low-income AA children. Through collaboration and multiple data collection methods, partners identified communication strategies to overcome informational barriers. These initial findings indicated a peer-to-peer health information intervention, entitled “Set the Rules”, as the best strategy to increase awareness. …

Systemic Immunosuppression And Risk Of Age-Related Macular Degeneration, Harpal S. Sandhu, Joshua Lambert, Yan Xu, Henry J. Kaplan

Applied Statistics Laboratory Faculty Publications

A local immune response has been implicated in the pathogenesis of age-related macular degeneration (AMD), but it is unclear if systemic immunosuppressive/immunomodulatory therapy (IMT) protects against the onset and/or progression of AMD. We performed a retrospective cohort study using a Cox proportional hazards model of two cohorts. Cohort 1 included patients with stage V chronic kidney disease (CKD) status post kidney transplantation, on at least one IMT agent, and older than 50. Cohort 2 included patients with stage IV or V CKD who had not undergone kidney transplantation, were not on IMT, and were older than 50. The main outcomes …