Digital Commons Network^™

Intermittent Bolus Compared With Continuous Feeding Enhances Insulin And Amino Acid Signaling To Translation Initiation In Skeletal Muscle Of Neonatal Pigs, Agus Suryawan, Samer W El-Kadi, Hanh V Nguyen, Marta L Fiorotto, Teresa A Davis

Children’s Nutrition Research Center Staff Publications

Background: Nutrition administered as intermittent bolus feeds rather than continuously promotes greater protein synthesis rates in skeletal muscle and enhances lean growth in a neonatal piglet model. The molecular mechanisms responsible remain unclear.

Objectives: We aimed to identify the insulin- and/or amino acid-signaling components involved in the enhanced stimulation of skeletal muscle by intermittent bolus compared to continuous feeding in neonatal pigs born at term.

Methods: Term piglets (2-3 days old) were fed equal amounts of sow milk replacer [12.8 g protein and 155 kcal/(kg body weight · d)] by orogastric tube as intermittent bolus meals every 4 hours (INT) …

Phagocytes Produce Prostaglandin E2 In Response To Cytosolic Listeria Monocytogenes, Courtney E. Mcdougal, Zachary T. Morrow, Tighe Christopher, Seonyoung Kim, Drake Carter, David M. Stevenson, Daniel Amador-Noguez, Mark J. Miller, John-Demian Sauer

Open Access Publications

Listeria monocytogenes is an intracellular bacterium that elicits robust CD8+ T-cell responses. Despite the ongoing development of L. monocytogenes-based platforms as cancer vaccines, our understanding of how L. monocytogenes drives robust CD8+ T-cell responses remains incomplete. One overarching hypothesis is that activation of cytosolic innate pathways is critical for immunity, as strains of L. monocytogenes that are unable to access the cytosol fail to elicit robust CD8+ T-cell responses and in fact inhibit optimal T-cell priming. Counterintuitively, however, activation of known cytosolic pathways, such as the inflammasome and type I IFN, lead to impaired immunity. Conversely, production of prostaglandin E2 …

Exogenous Inter-Α Inhibitor Proteins Prevent Cell Death And Improve Ischemic Stroke Outcomes In Mice, Louise D Mccullough, Meaghan Roy-O'Reilly, Yun-Ju Lai, Anthony Patrizz, Yan Xu, Juneyoung Lee, Aleah Holmes, Daniel C Kraushaar, Anjali Chauhan, Lauren H Sansing, Barbara S Stonestreet, Liang Zhu, Julia Kofler, Yow-Pin Lim, Venugopal Reddy Venna

Faculty, Staff and Students Publications

Inter-α inhibitor proteins (IAIPs) are a family of endogenous plasma and extracellular matrix molecules. IAIPs suppress proinflammatory cytokines, limit excess complement activation, and bind extracellular histones to form IAIP-histone complexes, leading to neutralization of histone-associated cytotoxicity in models of sepsis. Many of these detrimental processes also play critical roles in the pathophysiology of ischemic stroke. In this study, we first assessed the clinical relevance of IAIPs in stroke and then tested the therapeutic efficacy of exogenous IAIPs in several experimental stroke models. IAIP levels were reduced in both ischemic stroke patients and in mice subjected to experimental ischemic stroke when …

Alzheimer's Disease Alters Oligodendrocytic Glycolytic And Ketolytic Gene Expression, Erin R Saito, Justin B Miller, Oscar Harari, Carlos Cruchaga, Kathie A Mihindukulasuriya, John S K Kauwe, Benjamin T Bikman

2020-Current year OA Pubs

INTRODUCTION: Sporadic Alzheimer's disease (AD) is strongly correlated with impaired brain glucose metabolism, which may affect AD onset and progression. Ketolysis has been suggested as an alternative pathway to fuel the brain.

METHODS: RNA-seq profiles of post mortem AD brains were used to determine whether dysfunctional AD brain metabolism can be determined by impairments in glycolytic and ketolytic gene expression. Data were obtained from the Knight Alzheimer's Disease Research Center (62 cases; 13 controls), Mount Sinai Brain Bank (110 cases; 44 controls), and the Mayo Clinic Brain Bank (80 cases; 76 controls), and were normalized to cell type: astrocytes, microglia, …

Telemedicine Visits In An Established Multidisciplinary Central Nervous System Clinic For Radiation Oncology And Neurosurgery (Radians) In A Community Hospital Setting., S C Bowen R, R Gheewala, Wa Paez, B Lucke-Wold, T Mitin, Jn Ciporen

Clinical Research and Leadership Faculty Publications

OBJECTIVE: To determine the impact of telemedicine visits, compared to in-person visits, on patient satisfaction in an established community hospital-based multidisciplinary central nervous system (CNS) clinic.

METHODS: Telemedicine options - virtual visits and teleconferencing - were introduced in July 2020. Both radiation oncologist and neurosurgeon were simultaneously present for the telemedicine visit. Descriptive patient demographics, survey responses, and travel time and distance calculations were analyzed. Satisfaction score was compared to previously published data.

RESULTS: A total of twenty-five telemedicine visits (n=22 video; n=3 phone) were completed since July 2020. Patient demographics are as follows: mean age was 59 years (range=22-81), …

Longitudinal Assessment Of Cytokine Expression And Plasminogen Activation In Hantavirus Cardiopulmonary Syndrome Reveals Immune Regulatory Dysfunction In End-Stage Disease, Peter Simons, Yan Guo, Virginie Bondu, Susan L. Tigert, Michelle Harkins, Samuel Goodfellow, Cana Tompkins, Devon Chabot-Richards, Xuexian O. Yang, Laura Gonzalez Bosc, Steven Bradfute, Daniel A. Lawrence, Tione Buranda

Pathology Research and Scholarship

Pathogenic New World orthohantaviruses cause hantavirus cardiopulmonary syndrome (HCPS), a severe immunopathogenic disease in humans manifested by pulmonary edema and respiratory distress, with case fatality rates approaching 40%. High levels of inflammatory mediators are present in the lungs and systemic circulation of HCPS patients. Previous studies have provided insights into the pathophysiology of HCPS. However, the longitudinal correlations of innate and adaptive immune responses and disease outcomes remain unresolved. This study analyzed serial immune responses in 13 HCPS cases due to Sin Nombre orthohantavirus (SNV), with 11 severe cases requiring extracorporeal membrane oxygenation (ECMO) treatment and two mild cases. We …

Cabotegravir For Hiv Prevention In Cisgender Men And Transgender Women, Raphael J Landovitz, Deborah Donnell, Meredith E Clement, Brett Hanscom, Leslie Cottle, Lara Coelho, Robinson Cabello, Suwat Chariyalertsak, Eileen F Dunne, Ian Frank, Jorge A Gallardo-Cartagena, Aditya H Gaur, Pedro Gonzales, Ha V Tran, Juan C Hinojosa, Esper G Kallas, Colleen F Kelley, Marcelo H Losso, J Valdez Madruga, Keren Middelkoop, Nittaya Phanuphak, Breno Santos, Omar Sued, Javier Valencia Huamaní, Edgar T Overton, Shobha Swaminathan, Carlos Del Rio, Roy M Gulick, Paul Richardson, Philip Sullivan, Estelle Piwowar-Manning, Mark Marzinke, Craig Hendrix, Maoji Li, Zhe Wang, Jeanne Marrazzo, Eric Daar, Aida Asmelash, Todd T Brown, Peter Anderson, Susan H Eshleman, Marcus Bryan, Cheryl Blanchette, Jonathan Lucas, Christina Psaros, Steven Safren, Jeremy Sugarman, Hyman Scott, Joseph J Eron, Sheldon D Fields, Nirupama D Sista, Kailazarid Gomez-Feliciano, Andrea Jennings, Ryan M Kofron, Timothy H Holtz, Katherine Shin, James F Rooney, Kimberly Y Smith, William Spreen, David Margolis, Alex Rinehart, Adeola Adeyeye, Myron S Cohen, Marybeth Mccauley, Beatriz Grinsztejn

Faculty, Staff and Student Publications

BACKGROUND: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection.

METHODS: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of …

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 …

Polyploid Giant Cancer Cells And Ovarian Cancer: New Insights Into Mitotic Regulators And Polyploidy†, Joanne S Richards, Nicholes R Candelaria, Rainer B Lanz

Faculty, Staff and Students Publications

Current first-line treatment of patients with high-grade serous ovarian cancer (HGSOC) involves the use of cytotoxic drugs that frequently lead to recurrent tumors exhibiting increased resistance to the drugs and poor patient survival. Strong evidence is accumulating to show that HGSOC tumors and cell lines contain a subset of cells called polyploidy giant cancer cells (PGCCs) that act as stem-like, self-renewing cells. These PGCCs appear to play a key role in tumor progression by generating drug-resistant progeny produced, in part, as a consequence of utilizing a modified form of mitosis known as endoreplication. Thus, developing drugs to target PGCCs and …

Beneficial Effects Of The 30-Minute Door-To-Needle Time Standard For Alteplase Administration, Suja S Rajan, Marquita Decker-Palmer, Jessica Wise, Thanh Dao, Cindy Salem, Sean I Savitz

Faculty and Staff Publications

Objective: The American Heart Association recently raised the bar on the timely treatment of acute ischemic stroke (AIS) with intravenous alteplase. Our study looks at the effectiveness of this new standard, by examining the effect of varying door-to-needle times of alteplase initiation on the clinical, quality of care, and efficiency of care outcomes.

Methods: This retrospective case-control study examined 752 AIS patients treated with intravenous alteplase in a large academic health system during 2015-2018, and compared their outcomes after treatment within 30, 45, and 60 min of arrival. The outcomes compared were: (1) clinical - discharge and 90-day modified Rankin …

Metabolomics Profiling Of Patients With A-Β+ Ketosis-Prone Diabetes During Diabetic Ketoacidosis, Farook Jahoor, Jean W Hsu, Paras B Mehta, Kelly R Keene, Ruchi Gaba, Surya Narayan Mulukutla, Eunice Caducoy, W Frank Peacock, Sanjeet G Patel, Rasmus Bennet, Ake Lernmark, Ashok Balasubramanyam

Faculty, Staff and Students Publications

When stable and near-normoglycemic, patients with “A−β+” ketosis-prone diabetes (KPD) manifest accelerated leucine catabolism and blunted ketone oxidation, which may underlie their proclivity to develop diabetic ketoacidosis (DKA). To understand metabolic derangements in A−β+ KPD patients during DKA, we compared serum metabolomics profiles of adults during acute hyperglycemic crises, without (n = 21) or with (n = 74) DKA, and healthy control subjects (n = 17). Based on 65 kDa GAD islet autoantibody status, C-peptide, and clinical features, 53 DKA patients were categorized as having KPD and 21 type 1 diabetes (T1D); 21 nonketotic patients were categorized as …

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 …

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 …

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 …

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 …

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

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 …

Homozygous Mtap Deletion In Primary Human Glioblastoma Is Not Associated With Elevation Of Methylthioadenosine, Yasaman Barekatain, Jeffrey J. Ackroyd, Victoria C. Yan, Sunada Khadka, Lin Wang, Ko-Chien Chen, Anton H. Poral, Theresa Tran, Dimitra K. Georgiou, Kenisha Arthur, Yu-Hsi Lin, Nikunj Satani, Elliot S. Ballato, Eliot I. Behr, Ana C. De Carvalho, Roel G.W. Verhaak, John De Groot, Jason T. Huse, John M. Asara, Raghu Kalluri, Florian L. Muller

Neurosurgery Articles

Homozygous deletion of methylthioadenosine phosphorylase (MTAP) in cancers such as glioblastoma represents a potentially targetable vulnerability. Homozygous MTAP-deleted cell lines in culture show elevation of MTAP's substrate metabolite, methylthioadenosine (MTA). High levels of MTA inhibit protein arginine methyltransferase 5 (PRMT5), which sensitizes MTAP-deleted cells to PRMT5 and methionine adenosyltransferase 2A (MAT2A) inhibition. While this concept has been extensively corroborated in vitro, the clinical relevance relies on exhibiting significant MTA accumulation in human glioblastoma. In this work, using comprehensive metabolomic profiling, we show that MTA secreted by MTAP-deleted cells in vitro results in high levels of extracellular MTA. We further demonstrate …

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

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 …

Long Non-Coding Rnas And Their Targets As Potential Biomarkers In Breast Cancer., Maryam Khalid, Rehan Zafar Paracha, Maryum Nisar, Sumaira Malik, Salma Tariq, Iqra Arshad, Amnah Siddiqa, Zamir Hussain, Jamil Ahmad, Amjad Ali

Faculty Research 2021

Breast cancer is among the lethal types of cancer with a high mortality rate, globally. Its high prevalence can be controlled through improved analysis and identification of disease-specific biomarkers. Recently, long non-coding RNAs (lncRNAs) have been reported as key contributors of carcinogenesis and regulate various cellular pathways through post-transcriptional regulatory mechanisms. The specific aim of this study was to identify the novel interactions of aberrantly expressed genetic components in breast cancer by applying integrative analysis of publicly available expression profiles of both lncRNAs and mRNAs. Differential expression patterns were identified by comparing the breast cancer expression profiles of samples with …

Socio-Demographic And Trauma-Related Predictors Of Ptsd Within 8 Weeks Of A Motor Vehicle Collision In The Aurora Study, Ronald C Kessler, Kerry J Ressler, Stacey L House, Francesca L Beaudoin, Xinming An, Jennifer S Stevens, Donglin Zeng, Thomas C Neylan, Sarah D Linnstaedt, Laura T Germine, Paul I Musey, Phyllis L Hendry, Sophia Sheikh, Alan B Storrow, Christopher W Jones, Brittany E Punches, Elizabeth M Datner, Kamran Mohiuddin, Nina T Gentile, Meghan E Mcgrath, Sanne J Van Rooij, Lauren A Hudak, John P Haran, David A Peak, Robert M Domeier, Claire Pearson, Leon D Sanchez, Niels K Rathlev, William F Peacock, Steven E Bruce, Mark W Miller, Jutta Joormann, Deanna M Barch, Diego A Pizzagalli, John F Sheridan, Jordan W Smoller, Thaddeus W W Pace, Steven E Harte, James M Elliott, Nathaniel G Harnett, Lauren A M Lebois, Irving Hwang, Nancy A Sampson, Karestan C Koenen, Samuel A Mclean

Faculty, Staff and Students Publications

This is the initial report of results from the AURORA multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience. We focus on n = 666 participants presenting to EDs following a motor vehicle collision (MVC) and examine associations of participant socio-demographic and participant-reported MVC characteristics with 8-week posttraumatic stress disorder (PTSD) adjusting for pre-MVC PTSD and mediated by peritraumatic symptoms and 2-week acute stress disorder (ASD). Peritraumatic Symptoms, ASD, and PTSD were assessed with self-report scales. Eight-week PTSD prevalence was relatively high (42.0%) and positively …

Case-Based Audit And Feedback Around A Decision Aid Improved Antibiotic Choice And Duration For Uncomplicated Cystitis In Primary Care Clinics, Larissa Grigoryan, Roger Zoorob, George Germanos, Mohamad Sidani, Matthew Horsfield, Fareed Khan, Mohammad Zare, Melanie Goebel, Robert Atmar, Barbara Trautner

Faculty, Staff and Students Publications

OBJECTIVES: The objective of our study was to evaluate the impact of a multifaceted stewardship intervention on adherence to the evidence-based practice guidelines on treatment of uncomplicated cystitis in primary care. We hypothesised that our intervention would increase guideline adherence in terms of antibiotic choice and duration of treatment.

DESIGN: A preintervention and postintervention comparison with a contemporaneous control group was performed. During the first two study periods, we obtained baseline data and performed interviews exploring provider prescribing decisions for cystitis at both clinics. During the third period in the intervention clinic only, the intervention included a didactic lecture, a …

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%). …

Sleep Apnea And Fetal Growth Restriction (Safer) Study: Protocol For A Pragmatic Randomised Clinical Trial Of Positive Airway Pressure As An Antenatal Therapy For Fetal Growth Restriction In Maternal Obstructive Sleep Apnoea, Alex Hincker, Jacob Nadler, Suzanne Karan, Ebony Carter, Shay Porat, Barbara Warner, Yo-El S Ju, Arbi Ben Abdallah, Elizabeth Wilson, Ellen M Lockhart, Yehuda Ginosar

Open Access Publications

INTRODUCTION: Fetal growth restriction (FGR) is a major contributor to fetal and neonatal morbidity and mortality with intrauterine, neonatal and lifelong complications. This study explores maternal obstructive sleep apnoea (OSA) as a potentially modifiable risk factor for FGR. We hypothesise that, in pregnancies complicated by FGR, treating mothers who have OSA using positive airway pressure (PAP) will improve birth weight and neonatal outcomes.

METHODS AND ANALYSIS: The Sleep Apnea and Fetal Growth Restriction study is a prospective, block-randomised, single-blinded, multicentre, pragmatic controlled trial. We enrol pregnant women aged 18-50, between 22 and 31 weeks of gestation, with established FGR based …

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

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 …

Brainstem Quadruple Aberrant Hyperphosphorylated Tau, Beta-Amyloid, Alpha-Synuclein And Tdp-43 Pathology, Stress And Sleep Behavior Disorders, Lilian Calderón-Garcidueñas, Ravi Philip Rajkumar, Elijah W. Stommel, Randy Kulesza, Yusra Mansour, Adriana Rico-Villanueva, Jorge Orlando Flores-Vázquez, Rafael Brito-Aguilar, Silvia Ramírez-Sánchez, Griselda García-Alonso, Diana A. Chávez-Franco, Samuel C. Luévano-Castro, Edgar García-Rojas, Paula Revueltas-Ficachi, Rodolfo Villarreal-Ríos, Partha S. Mukherjee

Otolaryngology Articles

Quadruple aberrant hyperphosphorylated tau (p-τ), amyloid-β peptide, alpha-synuclein and TDP-43 brainstem and supratentorial pathology are documented in forensic ≤40y autopsies in Metropolitan Mexico City (MMC), and p-τ is the major aberrant protein. Post-traumatic stress disorder (PTSD) is associated with an elevated risk of subsequent dementia, and rapid eye movement sleep behavior disorder (RBD) is documented in PD, AD, Lewy body dementia and ALS. This study aimed to identify an association between PTSD and potential pRBD in Mexico. An anonymous online survey of 4502 urban college-educated adults, 29.3 ± 10.3 years; MMC, n = 1865; non-MMC, n = 2637, measured PTSD …

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 …

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 …