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Musculoskeletal Injuries In Us Air Force Security Forces, January 2009 To December 2018, Julia N Sundstrom, Bryant J Webber, George L Delclos, John R Herbold, David Gimeno Ruiz De Porras Aug 2021

Musculoskeletal Injuries In Us Air Force Security Forces, January 2009 To December 2018, Julia N Sundstrom, Bryant J Webber, George L Delclos, John R Herbold, David Gimeno Ruiz De Porras

Faculty, Staff and Student Publications

OBJECTIVE: to determine the incidence, types, and risk factors of musculoskeletal injuries in a military security forces population.

METHODS: Demographic and diagnostic data were retrieved on enlisted US Air Force security forces personnel who served on active duty between January 2009 and December 2018. Incidence rates and ratios were calculated using Poisson regression.

RESULTS: During 251,787 person-years of exposure, 62,489 personnel served on active duty. Of these, 40,771 (65.2%) were diagnosed with at least one musculoskeletal injury. The majority (60.1%) of the 164,078 unique musculoskeletal injuries were inflammation and pain secondary to overuse. After adjusting for other factors, women had …


Comparative Effectiveness Of Sodium-Glucose Cotransporter 2 Inhibitors Vs Sulfonylureas In Patients With Type 2 Diabetes, Yan Xie, Benjamin Bowe, Andrew K Gibson, Janet B Mcgill, Geetha Maddukuri, Ziyad Al-Aly Aug 2021

Comparative Effectiveness Of Sodium-Glucose Cotransporter 2 Inhibitors Vs Sulfonylureas In Patients With Type 2 Diabetes, Yan Xie, Benjamin Bowe, Andrew K Gibson, Janet B Mcgill, Geetha Maddukuri, Ziyad Al-Aly

2020-Current year OA Pubs

IMPORTANCE: In the treatment of type 2 diabetes, evidence of the comparative effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors vs sulfonylureas-the second most widely used antihyperglycemic class after metformin-is lacking.

OBJECTIVE: To evaluate the comparative effectiveness of SGLT2 inhibitors and sulfonylureas associated with the risk of all-cause mortality among patients with type 2 diabetes using metformin.

DESIGN, SETTING, AND PARTICIPANTS: A cohort study used data from the US Department of Veterans Affairs compared the use of SGLT2 inhibitors vs sulfonylureas in individuals receiving metformin for treatment of type 2 diabetes. A total of 23 870 individuals with new use of …


Il-7 Expands Lymphocyte Populations And Enhances Immune Responses To Sipuleucel-T In Patients With Metastatic Castration-Resistant Prostate Cancer (Mcrpc), Russell K Pachynski, Chihiro Morishima, Et Al Aug 2021

Il-7 Expands Lymphocyte Populations And Enhances Immune Responses To Sipuleucel-T In Patients With Metastatic Castration-Resistant Prostate Cancer (Mcrpc), Russell K Pachynski, Chihiro Morishima, Et Al

2020-Current year OA Pubs

BACKGROUND: Sipuleucel-T (sip-T) is a Food and Drug Administration (FDA)-approved autologous cellular immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). We hypothesized that combining sip-T with interleukin (IL)-7, a homeostatic cytokine that enhances both B and T cell development and proliferation, would augment and prolong antigen-specific immune responses against both PA2024 (the immunogen for sip-T) and prostatic acid phosphatase (PAP).

METHODS: Fifty-four patients with mCRPC treated with sip-T were subsequently enrolled and randomized 1:1 into observation (n=26) or IL-7 (n=28) arms of a phase II clinical trial (NCT01881867). Recombinant human (rh) IL-7 (CYT107) was given weekly×4. Immune responses were evaluated using …


Sugar-Sweetened Beverage Consumption May Modify Associations Between Genetic Variants In The Chrebp (Carbohydrate Responsive Element Binding Protein) Locus And Hdl-C (High-Density Lipoprotein Cholesterol) And Triglyceride Concentrations, Danielle E Haslam, Gina M Peloso, Melanie Guirette, Fumiaki Imamura, Traci M Bartz, Achilleas N Pitsillides, Carol A Wang, Ruifang Li-Gao, Jason M Westra, Niina Pitkänen, Kristin L Young, Mariaelisa Graff, Alexis C Wood, Kim V E Braun, Jian'an Luan, Mika Kähönen, Jessica C Kiefte-De Jong, Mohsen Ghanbari, Nathan Tintle, Rozenn N Lemaitre, Dennis O Mook-Kanamori, Kari North, Mika Helminen, Yasmin Mossavar-Rahmani, Linda Snetselaar, Lisa W Martin, Jorma S Viikari, Wendy H Oddy, Craig E Pennell, Frits R Rosendall, M Arfan Ikram, Andre G Uitterlinden, Bruce M Psaty, Dariush Mozaffarian, Jerome I Rotter, Kent D Taylor, Terho Lehtimäki, Olli T Raitakari, Kara A Livingston, Trudy Voortman, Nita G Forouhi, Nick J Wareham, Renée De Mutsert, Steven S Rich, Joann E Manson, Samia Mora, Paul M Ridker, Jordi Merino, James B Meigs, Hassan S Dashti, Daniel I Chasman, Alice H Lichtenstein, Caren E Smith, Josée Dupuis, Mark A Herman, Nicola M Mckeown Aug 2021

Sugar-Sweetened Beverage Consumption May Modify Associations Between Genetic Variants In The Chrebp (Carbohydrate Responsive Element Binding Protein) Locus And Hdl-C (High-Density Lipoprotein Cholesterol) And Triglyceride Concentrations, Danielle E Haslam, Gina M Peloso, Melanie Guirette, Fumiaki Imamura, Traci M Bartz, Achilleas N Pitsillides, Carol A Wang, Ruifang Li-Gao, Jason M Westra, Niina Pitkänen, Kristin L Young, Mariaelisa Graff, Alexis C Wood, Kim V E Braun, Jian'an Luan, Mika Kähönen, Jessica C Kiefte-De Jong, Mohsen Ghanbari, Nathan Tintle, Rozenn N Lemaitre, Dennis O Mook-Kanamori, Kari North, Mika Helminen, Yasmin Mossavar-Rahmani, Linda Snetselaar, Lisa W Martin, Jorma S Viikari, Wendy H Oddy, Craig E Pennell, Frits R Rosendall, M Arfan Ikram, Andre G Uitterlinden, Bruce M Psaty, Dariush Mozaffarian, Jerome I Rotter, Kent D Taylor, Terho Lehtimäki, Olli T Raitakari, Kara A Livingston, Trudy Voortman, Nita G Forouhi, Nick J Wareham, Renée De Mutsert, Steven S Rich, Joann E Manson, Samia Mora, Paul M Ridker, Jordi Merino, James B Meigs, Hassan S Dashti, Daniel I Chasman, Alice H Lichtenstein, Caren E Smith, Josée Dupuis, Mark A Herman, Nicola M Mckeown

Faculty, Staff and Students Publications

BACKGROUND: ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the

METHODS: Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near

RESULTS: In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers …


De-Identification Procedures For Magnetic Resonance Images And The Impact On Structural Brain Measures At Different Ages, Elizabeth E L Buimer, Hugo G Schnack, Yaron Caspi, Neeltje E M Van Haren, Mikhail Milchenko, Pascal Pas, Alzheimer's Disease Neuroimaging Initiative, Hilleke E Hulshoff Pol, Rachel M Brouwer Aug 2021

De-Identification Procedures For Magnetic Resonance Images And The Impact On Structural Brain Measures At Different Ages, Elizabeth E L Buimer, Hugo G Schnack, Yaron Caspi, Neeltje E M Van Haren, Mikhail Milchenko, Pascal Pas, Alzheimer's Disease Neuroimaging Initiative, Hilleke E Hulshoff Pol, Rachel M Brouwer

2020-Current year OA Pubs

Surface rendering of MRI brain scans may lead to identification of the participant through facial characteristics. In this study, we evaluate three methods that overwrite voxels containing privacy-sensitive information: Face Masking, FreeSurfer defacing, and FSL defacing. We included structural T1-weighted MRI scans of children, young adults and older adults. For the young adults, test-retest data were included with a 1-week interval. The effects of the de-identification methods were quantified using different statistics to capture random variation and systematic noise in measures obtained through the FreeSurfer processing pipeline. Face Masking and FSL defacing impacted brain voxels in some scans especially in …


Long-Term Complications In Youth-Onset Type 2 Diabetes, Petter Bjornstad, Kimberly L Drews, Sonia Caprio, Rose Gubitosi-Klug, David M Nathan, Bereket Tesfaldet, Jeanie Tryggestad, Neil H White, Philip Zeitler, Today Study Group Jul 2021

Long-Term Complications In Youth-Onset Type 2 Diabetes, Petter Bjornstad, Kimberly L Drews, Sonia Caprio, Rose Gubitosi-Klug, David M Nathan, Bereket Tesfaldet, Jeanie Tryggestad, Neil H White, Philip Zeitler, Today Study Group

Open Access Publications

BACKGROUND: The prevalence of type 2 diabetes in youth is increasing, but little is known regarding the occurrence of related complications as these youths transition to adulthood.

METHODS: We previously conducted a multicenter clinical trial (from 2004 to 2011) to evaluate the effects of one of three treatments (metformin, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention) on the time to loss of glycemic control in participants who had onset of type 2 diabetes in youth. After completion of the trial, participants were transitioned to metformin with or without insulin and were enrolled in an observational follow-up study …


Influence Of Gender On Hours Of Supervised Library Use On Students’ Performance In Senior Secondary Schools In Imo State., Kelechi Ibegbulem Jul 2021

Influence Of Gender On Hours Of Supervised Library Use On Students’ Performance In Senior Secondary Schools In Imo State., Kelechi Ibegbulem

Library Philosophy and Practice (e-journal)

In this study, the researcher examined the influence of gender on hours of supervised library use on students’ performance in senior secondary schools in Imo State. Four objectives, four research questions were posed and four hypotheses formulated in the study. The study was carried out using quasi-experimental design which involved pre-test, treatment and post-test of non-equivalent group method. The population of the study was 94,963 Senior Secondary School Students (SS1-SS3) from 275 public secondary schools in Imo State. The sample size for the study comprised of 127 senior secondary II students drawn from three senior public secondary schools in Imo …


Therapeutic Efficacy Of A Potent Anti-Venezuelan Equine Encephalitis Virus Antibody Is Contingent On Fc Effector Function, Vanja Krneta-Stankic, Mark E Corkins, Adriana Paulucci-Holthauzen, Malgorzata Kloc, Andrew B Gladden, Rachel K Miller Jul 2021

Therapeutic Efficacy Of A Potent Anti-Venezuelan Equine Encephalitis Virus Antibody Is Contingent On Fc Effector Function, Vanja Krneta-Stankic, Mark E Corkins, Adriana Paulucci-Holthauzen, Malgorzata Kloc, Andrew B Gladden, Rachel K Miller

Faculty, Staff and Student Publications

E-cadherin junctions facilitate assembly and disassembly of cell contacts that drive development and homeostasis of epithelial tissues. In this study, using Xenopus embryonic kidney and Madin-Darby canine kidney (MDCK) cells, we investigate the role of the Wnt/planar cell polarity (PCP) formin Daam1 (Dishevelled-associated activator of morphogenesis 1) in regulating E-cadherin-based intercellular adhesion. Using live imaging, we show that Daam1 localizes to newly formed cell contacts in the developing nephron. Furthermore, analyses of junctional filamentous actin (F-actin) upon Daam1 depletion indicate decreased microfilament localization and slowed turnover. We also show that Daam1 is necessary for efficient and timely localization of junctional …


Covid-19 And The Impact On Rural And Black Church Congregants: Results Of The C-M-C Project, Lovoria B. Williams, Anita F. Fernander, Tofial Azam, Maria L. Gomez, Junghee Kang, Cassidy L. Moody, Hannah Bowman, Nancy E. Schoenberg Jul 2021

Covid-19 And The Impact On Rural And Black Church Congregants: Results Of The C-M-C Project, Lovoria B. Williams, Anita F. Fernander, Tofial Azam, Maria L. Gomez, Junghee Kang, Cassidy L. Moody, Hannah Bowman, Nancy E. Schoenberg

Nursing Faculty Publications

The COVID-19 pandemic has had devastating effects on Black and rural populations with a mortality rate among Blacks three times that of Whites and both rural and Black populations experiencing limited access to COVID-19 resources. The primary purpose of this study was to explore the health, financial, and psychological impact of COVID-19 among rural White Appalachian and Black nonrural central Kentucky church congregants. Secondarily we sought to examine the association between sociodemographics and behaviors, attitudes, and beliefs regarding COVID-19 and intent to vaccinate. We used a cross sectional survey design developed with the constructs of the Health Belief and Theory …


Leveraging Big Data For Pattern Recognition Of Socio-Demographic And Climatic Factors In Correlation With Eye Disorders In Telangana State, India, Amna Alalawi, Les Sztandera, Parth Lalakia, Anthony Vipin Das, Sai Prashanthi Gumpili, Richard Derman Jul 2021

Leveraging Big Data For Pattern Recognition Of Socio-Demographic And Climatic Factors In Correlation With Eye Disorders In Telangana State, India, Amna Alalawi, Les Sztandera, Parth Lalakia, Anthony Vipin Das, Sai Prashanthi Gumpili, Richard Derman

Kanbar College Faculty Papers

Purpose: Big data is the new gold, especially in health care. Advances in collecting and processing electronic medical records (EMR) coupled with increasing computer capabilities have resulted in an increased interest in the use of big data in health care. Ophthalmology has been an area of focus where results have shown to be promising. The objective of this study was to determine whether the EMR at a multi-tier ophthalmology network in India can contribute to the management of patient care, through studying how climatic and socio-demographic factors relate to eye disorders and visual impairment in the State of Telangana.

Methods: …


Alterations In Cerebral Glucose Metabolism As Measured By 18f-Fluorodeoxyglucose-Pet In Patients With Persistent Postconcussion Syndrome., Eric M Teichner, Jason C You, Chloe Hriso, Nancy A Wintering, George P Zabrecky, Abass Alavi, Anthony J Bazzan, Daniel A Monti, Andrew B Newberg Jul 2021

Alterations In Cerebral Glucose Metabolism As Measured By 18f-Fluorodeoxyglucose-Pet In Patients With Persistent Postconcussion Syndrome., Eric M Teichner, Jason C You, Chloe Hriso, Nancy A Wintering, George P Zabrecky, Abass Alavi, Anthony J Bazzan, Daniel A Monti, Andrew B Newberg

Department of Medicine Faculty Papers

BACKGROUND: Many patients who have traumatic brain injury experience a wide range of psychiatric and neurological symptoms (including impairment in functional status, cognition, and mood), and if persistent are referred to as persistent postconcussion syndrome (PCS). To our knowledge, this is the first study to broadly evaluate metabolic dysregulation in a heterogenous patient population meeting the criteria for PCS.

METHODS: A total of 64 PCS patients and 37 healthy controls underwent 18F-fluorodeoxyglucose-PET (18F-FDG-PET) scanning, and 70 brain structures (including left and right structures where appropriate) were analyzed in each subject.

RESULTS: Compared to the brains of healthy controls, those of …


Monitoring Self-Perceived Occupational Health Inequities In Central America, 2011 And 2018, Michael Silva-Peñaherrera, David Gimeno Ruiz De Porras, George L Delclos, Marianela Rojas Garbanzo, Pamela Merino-Salazar, Maria Lopez-Ruiz, Fernando G Benavides Jul 2021

Monitoring Self-Perceived Occupational Health Inequities In Central America, 2011 And 2018, Michael Silva-Peñaherrera, David Gimeno Ruiz De Porras, George L Delclos, Marianela Rojas Garbanzo, Pamela Merino-Salazar, Maria Lopez-Ruiz, Fernando G Benavides

Faculty, Staff and Student Publications

Objectives. to analyze changes in occupational health inequity between 2011 and 2018 among workers in Central America. Methods. Data were collected by face-to-face interviews at the workers' homes for the 2 Central America Working Conditions Surveys (n = 12 024 in 2011 and n = 9030 in 2018). We estimated health inequity gaps by means of absolute and relative population attributable risks and the weighted Keppel index. We stratified all analyses by gender. Results. Between 2011 and 2018, the proportion of workers reporting poor self-perceived health decreased both in women (from 32% to 29%) and men (from 33% to 30%). …


Barbadin Potentiates Long-Term Effects Of Lorcaserin On Pomc Neurons And Weight Loss, Yang He, Hailan Liu, Na Yin, Yongjie Yang, Chunmei Wang, Meng Yu, Hesong Liu, Chen Liang, Julia Wang, Longlong Tu, Nan Zhang, Lina Wang, Yanlin He, Makoto Fukuda, Qi Wu, Zheng Sun, Qingchun Tong, Yong Xu Jun 2021

Barbadin Potentiates Long-Term Effects Of Lorcaserin On Pomc Neurons And Weight Loss, Yang He, Hailan Liu, Na Yin, Yongjie Yang, Chunmei Wang, Meng Yu, Hesong Liu, Chen Liang, Julia Wang, Longlong Tu, Nan Zhang, Lina Wang, Yanlin He, Makoto Fukuda, Qi Wu, Zheng Sun, Qingchun Tong, Yong Xu

Children’s Nutrition Research Center Staff Publications

Obesity is a serious global health problem because of its increasing prevalence and comorbidities, but its treatments are limited. The serotonin 2C receptor (5-HT2CR), a G-protein-coupled receptor, activates proopiomelanocortin (POMC) neurons in the arcuate nucleus of hypothalamus (ARH) to reduce appetite and weight gain. However, several 5-HT analogs targeting this receptor, e.g., lorcaserin (Lor), suffer from diminished efficacy to reduce weight after prolonged administration. Here, we show that barbadin (Bar), a novel β-arrestin/β2-adaptin inhibitor, can prevent 5-HT2CR internalization in cells and potentiate long-term effects of Lor to reduce appetite and body weight in male mice. Mechanistically, …


Distress Evaluation In A Veteran Affairs Oncology Clinic, Reena Jayani, Ronald J. Markert, Amy Heard, Geetika Kumar Jun 2021

Distress Evaluation In A Veteran Affairs Oncology Clinic, Reena Jayani, Ronald J. Markert, Amy Heard, Geetika Kumar

Internal Medicine Faculty Publications

Distress in oncology patients (pts) has a negative impact on quality of life, survival, and healthcare satisfaction. Higher distress leads to lower compliance with treatment and follow-up [1-8]. The 2012 American College of Surgeons Commission on Cancer (CoC) standard of care for oncology pts included an assessment for distress [1]. A screening process for distress allows the healthcare team to address these issues early and refer to appropriate resources [2-9]. This project was initiated to meet National Comprehensive Cancer Network (NCCN) and CoC standard of care, identify distress in veterans with cancer, and address these concerns. Patients who attended the …


Sotorasib For Lung Cancers With Kras P.G12c Mutation, Ferdinandos Skoulidis, Ramaswamy Govindan, Et Al Jun 2021

Sotorasib For Lung Cancers With Kras P.G12c Mutation, Ferdinandos Skoulidis, Ramaswamy Govindan, Et Al

Open Access Publications

BACKGROUND: Sotorasib showed anticancer activity in patients with

METHODS: In a single-group, phase 2 trial, we investigated the activity of sotorasib, administered orally at a dose of 960 mg once daily, in patients with

RESULTS: Among the 126 enrolled patients, the majority (81.0%) had previously received both platinum-based chemotherapy and inhibitors of programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1). According to central review, 124 patients had measurable disease at baseline and were evaluated for response. An objective response was observed in 46 patients (37.1%; 95% confidence interval [CI], 28.6 to 46.2), including in 4 (3.2%) who had …


Ketogenic Diet Restrains Aging-Induced Exacerbation Of Coronavirus Infection In Mice, Seungjin Ryu, Irina Shchukina, Maxim Artyomov, Et Al Jun 2021

Ketogenic Diet Restrains Aging-Induced Exacerbation Of Coronavirus Infection In Mice, Seungjin Ryu, Irina Shchukina, Maxim Artyomov, Et Al

Open Access Publications

Increasing age is the strongest predictor of risk of COVID-19 severity and mortality. Immunometabolic switch from glycolysis to ketolysis protects against inflammatory damage and influenza infection in adults. To investigate how age compromises defense against coronavirus infection, and whether a pro-longevity ketogenic diet (KD) impacts immune surveillance, we developed an aging model of natural murine beta coronavirus (mCoV) infection with mouse hepatitis virus strain-A59 (MHV-A59). When inoculated intranasally, mCoV is pneumotropic and recapitulates several clinical hallmarks of COVID-19 infection. Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue, and hypothalamus, including neutrophilia and loss …


Dietary Fiber Intake, The Gut Microbiome, And Chronic Systemic Inflammation In A Cohort Of Adult Men, Wenjie Ma, Yin Cao, Et Al. Jun 2021

Dietary Fiber Intake, The Gut Microbiome, And Chronic Systemic Inflammation In A Cohort Of Adult Men, Wenjie Ma, Yin Cao, Et Al.

2020-Current year OA Pubs

BACKGROUND: A higher intake of dietary fiber is associated with a decreased risk of chronic inflammatory diseases such as cardiovascular disease and inflammatory bowel disease. This may function in part due to abrogation of chronic systemic inflammation induced by factors such as dysbiotic gut communities. Data regarding the detailed influences of long-term and recent intake of differing dietary fiber sources on the human gut microbiome are lacking.

METHODS: In a cohort of 307 generally healthy men, we examined gut microbiomes, profiled by shotgun metagenomic and metatranscriptomic sequencing, and long-term and recent dietary fiber intake in relation to plasma levels of …


Nlrp3 Inflammasome Is A Key Driver Of Obesity-Induced Atrial Arrhythmias, Larry Scott, Anke C Fender, Arnela Saljic, Luge Li, Xiaohui Chen, Xiaolei Wang, Dominik Linz, Jilu Lang, Mathias Hohl, Darragh Twomey, Thuy T Pham, Rodrigo Diaz-Lankenau, Mihail G Chelu, Markus Kamler, Mark L Entman, George E Taffet, Prashanthan Sanders, Dobromir Dobrev, Na Li Jun 2021

Nlrp3 Inflammasome Is A Key Driver Of Obesity-Induced Atrial Arrhythmias, Larry Scott, Anke C Fender, Arnela Saljic, Luge Li, Xiaohui Chen, Xiaolei Wang, Dominik Linz, Jilu Lang, Mathias Hohl, Darragh Twomey, Thuy T Pham, Rodrigo Diaz-Lankenau, Mihail G Chelu, Markus Kamler, Mark L Entman, George E Taffet, Prashanthan Sanders, Dobromir Dobrev, Na Li

Faculty, Staff and Students Publications

AIMS: Obesity, an established risk factor of atrial fibrillation (AF), is frequently associated with enhanced inflammatory response. However, whether inflammatory signaling is causally linked to AF pathogenesis in obesity remains elusive. We recently demonstrated that the constitutive activation of the 'NACHT, LRR, and PYD Domains-containing Protein 3' (NLRP3) inflammasome promotes AF susceptibility. In this study, we hypothesized that the NLRP3 inflammasome is a key driver of obesity-induced AF.

METHODS AND RESULTS: Western blotting was performed to determine the level of NLRP3 inflammasome activation in atrial tissues of obese patients, sheep, and diet-induced obese (DIO) mice. The increased body weight in …


Deciphering An Agrp-Serotoninergic Neural Circuit In Distinct Control Of Energy Metabolism From Feeding, Yong Han, Guobin Xia, Dollada Srisai, Fantao Meng, Yanlin He, Yali Ran, Yang He, Monica Farias, Giang Hoang, István Tóth, Marcelo O Dietrich, Miao-Hsueh Chen, Yong Xu, Qi Wu Jun 2021

Deciphering An Agrp-Serotoninergic Neural Circuit In Distinct Control Of Energy Metabolism From Feeding, Yong Han, Guobin Xia, Dollada Srisai, Fantao Meng, Yanlin He, Yali Ran, Yang He, Monica Farias, Giang Hoang, István Tóth, Marcelo O Dietrich, Miao-Hsueh Chen, Yong Xu, Qi Wu

Children’s Nutrition Research Center Staff Publications

Contrasting to the established role of the hypothalamic agouti-related protein (AgRP) neurons in feeding regulation, the neural circuit and signaling mechanisms by which they control energy expenditure remains unclear. Here, we report that energy expenditure is regulated by a subgroup of AgRP neurons that send non-collateral projections to neurons within the dorsal lateral part of dorsal raphe nucleus (dlDRN) expressing the melanocortin 4 receptor (MC4R), which in turn innervate nearby serotonergic (5-HT) neurons. Genetic manipulations reveal a bi-directional control of energy expenditure by this circuit without affecting food intake. Fiber photometry and electrophysiological results indicate that the thermo-sensing MC4RdlDRN neurons …


Mitochondrial Genome Copy Number Measured By Dna Sequencing In Human Blood Is Strongly Associated With Metabolic Traits Via Cell-Type Composition Differences, Liron Ganel, Lei Chen, Ryan Christ, Erica Young, Indraniel Das, Krishna Kanchi, David Larson, Allison Regier, Haley Abel, Chul Joo Kang, Alexandra Scott, Adam Locke, Nathan O Stitziel, Ira M Hall, Et Al Jun 2021

Mitochondrial Genome Copy Number Measured By Dna Sequencing In Human Blood Is Strongly Associated With Metabolic Traits Via Cell-Type Composition Differences, Liron Ganel, Lei Chen, Ryan Christ, Erica Young, Indraniel Das, Krishna Kanchi, David Larson, Allison Regier, Haley Abel, Chul Joo Kang, Alexandra Scott, Adam Locke, Nathan O Stitziel, Ira M Hall, Et Al

2020-Current year OA Pubs

BACKGROUND: Mitochondrial genome copy number (MT-CN) varies among humans and across tissues and is highly heritable, but its causes and consequences are not well understood. When measured by bulk DNA sequencing in blood, MT-CN may reflect a combination of the number of mitochondria per cell and cell-type composition. Here, we studied MT-CN variation in blood-derived DNA from 19184 Finnish individuals using a combination of genome (N = 4163) and exome sequencing (N = 19034) data as well as imputed genotypes (N = 17718).

RESULTS: We identified two loci significantly associated with MT-CN variation: a common variant at the MYB-HBS1L locus …


Defining Vdr Expression In The Brain Using A Novel Vdrcre Mouse, Hailan Liu, Yang He, Jessie Beck, Silvania Da Silva Teixeira, Keisha Harrison, Yong Xu, Stephanie Sisley Jun 2021

Defining Vdr Expression In The Brain Using A Novel Vdrcre Mouse, Hailan Liu, Yang He, Jessie Beck, Silvania Da Silva Teixeira, Keisha Harrison, Yong Xu, Stephanie Sisley

Children’s Nutrition Research Center Staff Publications

Vitamin D action has been linked to several diseases regulated by the brain including obesity, diabetes, autism, and Parkinson’s. However, the location of the vitamin D receptor (VDR) in the brain is not clear due to conflicting reports. We found that two antibodies previously published as specific in peripheral tissues are not specific in the brain. We thus created a new knockin mouse with cre recombinase expression under the control of the endogenous VDR promoter (VDRCre). We demonstrated that the cre activity in the VDRCre mouse brain (as reported by a cre-dependent tdTomato expression) is highly overlapping with endogenous VDR …


Evaluation Of Diazepam Nasal Spray In Patients With Epilepsy Concomitantly Using Maintenance Benzodiazepines: An Interim Subgroup Analysis From A Phase 3, Long-Term, Open-Label Safety Study., Eric B Segal, Daniel Tarquinio, Ian Miller, James W Wheless, Dennis Dlugos, Victor Biton, Gregory D Cascino, Jay Desai, R Edward Hogan, Kore Liow, Michael R Sperling, Blanca Vazquez, David F Cook, Adrian L Rabinowicz, Enrique Carrazana Jun 2021

Evaluation Of Diazepam Nasal Spray In Patients With Epilepsy Concomitantly Using Maintenance Benzodiazepines: An Interim Subgroup Analysis From A Phase 3, Long-Term, Open-Label Safety Study., Eric B Segal, Daniel Tarquinio, Ian Miller, James W Wheless, Dennis Dlugos, Victor Biton, Gregory D Cascino, Jay Desai, R Edward Hogan, Kore Liow, Michael R Sperling, Blanca Vazquez, David F Cook, Adrian L Rabinowicz, Enrique Carrazana

Department of Neurology Faculty Papers

OBJECTIVE: Diazepam nasal spray (Valtoco), indicated for acute treatment of frequent seizure activity (seizure clusters) in patients with epilepsy ≥6 years of age, is designed to be a rapid, noninvasive, socially acceptable route of administration. This interim analysis evaluated the safety profile of diazepam nasal spray in patients with and without concomitant use of benzodiazepines, with use of a second dose for a seizure cluster as a proxy for effectiveness.

METHODS: A long-term, phase 3, open-label safety study enrolled patients with epilepsy who had seizures despite a stable antiseizure medication regimen.

RESULTS: Among 175 patients enrolled by October 31, 2019, …


Psychological Impact Of Genetic And Clinical Screening For Pulmonary Fibrosis On Asymptomatic First-Degree Relatives Of Affected Individuals, Nikkola Carmichael, Jose M Martinez Manzano, Luisa D Quesada-Arias, Sergio De Frías Poli, Maura Alvarez Baumgartner, Maria A Planchart Ferretto, Lisa Digianni, Shannon Gampala-Sagar, Dominick A Leone, Swati Gulati, Souheil Y El-Chemaly, Hilary J Goldberg, Rachel Putman, Hiroto Hatabu, Ivan O Rosas, Gary M Hunninghake, Benjamin A Raby Jun 2021

Psychological Impact Of Genetic And Clinical Screening For Pulmonary Fibrosis On Asymptomatic First-Degree Relatives Of Affected Individuals, Nikkola Carmichael, Jose M Martinez Manzano, Luisa D Quesada-Arias, Sergio De Frías Poli, Maura Alvarez Baumgartner, Maria A Planchart Ferretto, Lisa Digianni, Shannon Gampala-Sagar, Dominick A Leone, Swati Gulati, Souheil Y El-Chemaly, Hilary J Goldberg, Rachel Putman, Hiroto Hatabu, Ivan O Rosas, Gary M Hunninghake, Benjamin A Raby

Faculty, Staff and Students Publications

Screening for pulmonary fibrosis may help to identify early stages of the disease. We assessed the psychological impact of screening undiagnosed first-degree relatives of patients with pulmonary fibrosis by administering two validated measures after participants received their results: the Decisional Regret Scale and the Feelings About genomiC Testing Results Questionnaire. More than 90% of relatives reported either no or mild decisional regret. Increased measures of decisional regret and negative feelings were present in those found to have a low diffusion capacity of carbon monoxide or interstitial lung abnormalities. Results of telomere length and genetic testing did not significantly impact regret.


Outcomes And Risk Factors Associated With Sars-Cov-2 Infection In A North American Registry Of Patients With Multiple Sclerosis, Amber Salter, Robert J Fox, Scott D Newsome, June Halper, David K B Li, Pamela Kanellis, Kathleen Costello, Bruce Bebo, Kottil Rammohan, Gary R Cutter, Anne H Cross Jun 2021

Outcomes And Risk Factors Associated With Sars-Cov-2 Infection In A North American Registry Of Patients With Multiple Sclerosis, Amber Salter, Robert J Fox, Scott D Newsome, June Halper, David K B Li, Pamela Kanellis, Kathleen Costello, Bruce Bebo, Kottil Rammohan, Gary R Cutter, Anne H Cross

2020-Current year OA Pubs

Importance: Emergence of SARS-CoV-2 causing COVID-19 prompted the need to gather information on clinical outcomes and risk factors associated with morbidity and mortality in patients with multiple sclerosis (MS) and concomitant SARS-CoV-2 infections.

Objective: To examine outcomes and risk factors associated with COVID-19 clinical severity in a large, diverse cohort of North American patients with MS.

Design, Setting, and Participants: This analysis used deidentified, cross-sectional data on patients with MS and SARS-CoV-2 infection reported by health care professionals in North American academic and community practices between April 1, 2020, and December 12, 2020, in the COVID-19 Infections in MS Registry. …


Experience With Liposomal Amphotericin B In Outpatient Parenteral Antimicrobial Therapy, Yvonne J Burnett, Andrej Spec, Mohamed M Ahmed, William G Powderly, Yasir Hamad May 2021

Experience With Liposomal Amphotericin B In Outpatient Parenteral Antimicrobial Therapy, Yvonne J Burnett, Andrej Spec, Mohamed M Ahmed, William G Powderly, Yasir Hamad

Open Access Publications

Outpatient parenteral antimicrobial therapy (OPAT) is a safe, effective, and convenient treatment strategy for patients receiving intravenous antimicrobials in the outpatient setting; however, data are limited describing the use and safety of liposomal amphotericin B (L-AMB). Records of patients receiving L-AMB OPAT between 1/1/2015 and 7/31/2018 were retrospectively reviewed. The primary objective was to describe the OPAT patient population discharged on L-AMB and evaluate factors associated with readmission and adverse events (AEs). Analysis was performed to evaluate for predictors of worse outcomes. Forty-two patients (67% male, median age 50 years) were identified, most of whom were treated for histoplasmosis. The …


Consumption Of High-Fructose Corn Syrup Compared With Sucrose Promotes Adiposity And Increased Triglyceridemia But Comparable Nafld Severity In Juvenile Iberian Pigs, Magdalena Maj, Brooke Harbottle, Payton A Thomas, Gabriella V Hernandez, Victoria A Smith, Mark S Edwards, Rob K Fanter, Hunter S Glanz, Chad Immoos, Douglas G Burrin, Tasha M Santiago-Rodriguez, Michael R La Frano, Rodrigo Manjarín May 2021

Consumption Of High-Fructose Corn Syrup Compared With Sucrose Promotes Adiposity And Increased Triglyceridemia But Comparable Nafld Severity In Juvenile Iberian Pigs, Magdalena Maj, Brooke Harbottle, Payton A Thomas, Gabriella V Hernandez, Victoria A Smith, Mark S Edwards, Rob K Fanter, Hunter S Glanz, Chad Immoos, Douglas G Burrin, Tasha M Santiago-Rodriguez, Michael R La Frano, Rodrigo Manjarín

Children’s Nutrition Research Center Staff Publications

Background: Fructose consumption has been linked to nonalcoholic fatty liver disease (NAFLD) in children. However, the effect of high-fructose corn syrup (HFCS) compared with sucrose in pediatric NAFLD has not been investigated.

Objectives: We tested whether the isocaloric substitution of dietary sucrose by HFCS would increase the severity of NAFLD in juvenile pigs, and whether this effect would be associated with changes in gut histology, SCFA production, and microbial diversity.

Methods: Iberian pigs, 53-d-old and pair-housed in pens balanced for weight and sex, were randomly assigned to receive a mash diet top-dressed with increasing amounts of sucrose (SUC; n = …


The Impact Of Erythropoietin On Short- And Long-Term Kidney-Related Outcomes In Neonates Of Extremely Low Gestational Age. Results Of A Multicenter, Double-Blind, Placebo-Controlled Randomized Clinical Trial, David J. Askenazi, Patrick J. Heagerty, Robert H. Schmicker, Patrick Brophy, Sandra E. Juul, Stuart L. Goldstein, Sangeeta Hingorani, Jean Lowe, Penut Trial Consortium May 2021

The Impact Of Erythropoietin On Short- And Long-Term Kidney-Related Outcomes In Neonates Of Extremely Low Gestational Age. Results Of A Multicenter, Double-Blind, Placebo-Controlled Randomized Clinical Trial, David J. Askenazi, Patrick J. Heagerty, Robert H. Schmicker, Patrick Brophy, Sandra E. Juul, Stuart L. Goldstein, Sangeeta Hingorani, Jean Lowe, Penut Trial Consortium

Pediatrics Research and Scholarship

OBJECTIVE: To evaluate whether extremely low gestational age neonates (ELGANs) randomized to erythropoietin have better or worse kidney-related outcomes during hospitalization and at 22-26 months of corrected gestational age (cGA) compared with those randomized to placebo.

STUDY DESIGN: We performed an ancillary study to a multicenter double-blind, placebo-controlled randomized clinical trial of erythropoietin in ELGANs.

RESULTS: The prevalence of severe (stage 2 or 3) acute kidney injury (AKI) was 18.2%. We did not find a statistically significant difference between those randomized to erythropoietin vs placebo for in-hospital primary (severe AKI) or secondary outcomes (any AKI and serum creatinine/cystatin C values …


Umbilical Cord Milking Vs Delayed Cord Clamping And Associations With In-Hospital Outcomes Among Extremely Premature Infants, Neha Kumbhat, Barry Eggleston, Alexis S. Davis, Sara B. Demauro, Krisa P. Van Meurs, Elizabeth E. Foglia, Satyan Lakshminrusimha, Michele C. Walsh, Kristi L. Watterberg, Myra H. Wyckoff, Abhik Das, Sara C. Handley, Generic Database Subcommittee Of The Nichd Neonatal Research Network May 2021

Umbilical Cord Milking Vs Delayed Cord Clamping And Associations With In-Hospital Outcomes Among Extremely Premature Infants, Neha Kumbhat, Barry Eggleston, Alexis S. Davis, Sara B. Demauro, Krisa P. Van Meurs, Elizabeth E. Foglia, Satyan Lakshminrusimha, Michele C. Walsh, Kristi L. Watterberg, Myra H. Wyckoff, Abhik Das, Sara C. Handley, Generic Database Subcommittee Of The Nichd Neonatal Research Network

Pediatrics Research and Scholarship

OBJECTIVE: To compare in-hospital outcomes after umbilical cord milking vs delayed cord clamping among infantsgestation.

STUDY DESIGN: Multicenter retrospective study of infants born(grade III or IV) intraventricular hemorrhage (IVH) by 36 weeks of postmenstrual age (PMA). Secondary outcomes assessed at 36 weeks of PMA were mortality, severe IVH, any IVH or mortality, and a composite of mortality or major morbidity. Outcomes were assessed using multivariable regression, incorporating mortality risk factors identified a priori, confounders, and center. A prespecified, exploratory analysis evaluated severe IVH in 2 gestational age strata, 22-24

RESULTS: Among 1834 infants, 23.6% were exposed to umbilical cord milking …


Type 2 Diabetes Subgroups, Risk For Complications, And Differential Effects Due To An Intensive Lifestyle Intervention, Michael P Bancks, Haiying Chen, Ashok Balasubramanyam, Alain G Bertoni, Mark A Espeland, Steven E Kahn, Scott Pilla, Elizabeth Vaughan, Lynne E Wagenknecht May 2021

Type 2 Diabetes Subgroups, Risk For Complications, And Differential Effects Due To An Intensive Lifestyle Intervention, Michael P Bancks, Haiying Chen, Ashok Balasubramanyam, Alain G Bertoni, Mark A Espeland, Steven E Kahn, Scott Pilla, Elizabeth Vaughan, Lynne E Wagenknecht

Faculty, Staff and Students Publications

OBJECTIVE: We reevaluated the Action for Health in Diabetes (Look AHEAD) intervention, incorporating diabetes subgroups, to identify whether intensive lifestyle intervention (ILI) is associated with differential risk for cardiovascular disease (CVD) by diabetes subgroup.

RESEARCH DESIGN AND METHODS: In the Look AHEAD trial, 5,145 participants, aged 45-76 years, with type 2 diabetes (T2D) and overweight or obesity were randomly assigned to 10 years of ILI or a control condition of diabetes support and education. The ILI focused on weight loss through decreased caloric intake and increased physical activity. To characterize diabetes subgroups, we applied k-means clustering to data on age …


Exercise-Induced Alterations In Phospholipid Hydrolysis, Airway Surfactant, And Eicosanoids And Their Role In Airway Hyperresponsiveness In Asthma, Ryan C Murphy, Ying Lai, James D Nolin, Robier A Aguillon Prada, Arindam Chakrabarti, Michael V Novotny, Michael C Seeds, William A Altemeier, Michael H Gelb, Robert Duncan Hite, Teal S Hallstrand May 2021

Exercise-Induced Alterations In Phospholipid Hydrolysis, Airway Surfactant, And Eicosanoids And Their Role In Airway Hyperresponsiveness In Asthma, Ryan C Murphy, Ying Lai, James D Nolin, Robier A Aguillon Prada, Arindam Chakrabarti, Michael V Novotny, Michael C Seeds, William A Altemeier, Michael H Gelb, Robert Duncan Hite, Teal S Hallstrand

Faculty, Staff and Student Publications

The mechanisms responsible for driving endogenous airway hyperresponsiveness (AHR) in the form of exercise-induced bronchoconstriction (EIB) are not fully understood. We examined alterations in airway phospholipid hydrolysis, surfactant degradation, and lipid mediator release in relation to AHR severity and changes induced by exercise challenge. Paired induced sputum (