Digital Commons Network^™

25-Hydroxycholesterol Amplifies Microglial Il-1Β Production In An Apoe Isoform-Dependent Manner, Man Ying Wong, Michael Lewis, James J Doherty, Yang Shi, Anil G Cashikar, Anna Amelianchik, Svitlana Tymchuk, Patrick M Sullivan, Mingxing Qian, Douglas F Covey, Gregory A Petsko, David M Holtzman, Steven M Paul, Wenjie Luo

2020-Current year OA Pubs

BACKGROUND: Genome-wide association studies of Alzheimer's disease (AD) have implicated pathways related to lipid homeostasis and innate immunity in AD pathophysiology. However, the exact cellular and chemical mediators of neuroinflammation in AD remain poorly understood. The oxysterol 25-hydroxycholesterol (25-HC) is an important immunomodulator produced by peripheral macrophages with wide-ranging effects on cell signaling and innate immunity. Cholesterol 25-hydroxylase (CH25H), the enzyme responsible for 25-HC production, has also been found to be one of the disease-associated microglial (DAM) genes that are upregulated in the brain of AD and AD transgenic mouse models.

METHODS: We used real-time PCR and immunoblotting to examine …

Effect Of Continuous Glucose Monitoring On Hypoglycemia In Older Adults With Type 1 Diabetes: A Randomized Clinical Trial, Richard E. Pratley, Lauren G. Kanapka, Michael R. Rickels, Andrew Ahmann, Grazia Aleppo, Roy Beck, Anuj Bhargava, Bruce W. Bode, Anders Carlson, Naomi S. Chaytor, D Steven Fox, Robin Goland, Irl B. Hirsch, Davida F. Kruger, Yogish C. Kudva, Carol Levy, Janet B. Mcgill, Anne Peters, Louis Philipson, Athena Philis-Tsimikas, Rodica Pop-Busui, Viral N. Shah, Michael Thompson, Francesco Vendrame, Alandra Verdejo, Ruth S. Weinstock, Laura Young, Kellee M. Miller

Endocrinology Articles

Importance: Continuous glucose monitoring (CGM) provides real-time assessment of glucose levels and may be beneficial in reducing hypoglycemia in older adults with type 1 diabetes.

Objective: To determine whether CGM is effective in reducing hypoglycemia compared with standard blood glucose monitoring (BGM) in older adults with type 1 diabetes.

Design, Setting, and Participants: Randomized clinical trial conducted at 22 endocrinology practices in the United States among 203 adults at least 60 years of age with type 1 diabetes.

Interventions: Participants were randomly assigned in a 1:1 ratio to use CGM (n = 103) or standard BGM (n = 100).

Main …

Linking Activity, Nutrition, And Child Health (Launch): Protocol For A Longitudinal Cohort Study Of Children As They Develop From Infancy To Preschool Age, Russell R. Pate, Edward A. Frongillo Jr., Kerry Cordan, Marsha Dowda, Alexander C. Mclain, Myriam E. Torres, William H. Brown, Agnes Bucko, Emily R. Shull

Faculty Publications

Background

Physical activity is known to provide important health benefits in children ages 3 years and above, but little is known about the effects of physical activity on health in very young children under age 3. LAUNCH (Linking Activity, Nutrition, and Child Health) is a study designed to expand the body of knowledge on development of physical activity behavior and associations between physical activity and other health characteristics as children transition from infancy to preschool age.

Methods

Physical activity and sedentary behavior will be measured objectively in young children over a period of 30 months. Each child will complete a …

Covid-19 Medical Papers Have Fewer Women First Authors Than Expected., Jens Peter Andersen, Mathias Wullum Nielsen, Nicole L Simone, Resa E Lewiss, Reshma Jagsi

Department of Radiation Oncology Faculty Papers

The COVID-19 pandemic has resulted in school closures and distancing requirements that have disrupted both work and family life for many. Concerns exist that these disruptions caused by the pandemic may not have influenced men and women researchers equally. Many medical journals have published papers on the pandemic, which were generated by researchers facing the challenges of these disruptions. Here we report the results of an analysis that compared the gender distribution of authors on 1893 medical papers related to the pandemic with that on papers published in the same journals in 2019, for papers with first authors and last …

A Genome-Wide Association Study Identifies Two Novel Susceptible Regions For Squamous Cell Carcinoma Of The Head And Neck, Sanjay Shete, Hongliang Liu, Jian Wang, Robert Yu, Erich M Sturgis, Guojun Li, Kristina R Dahlstrom, Zhensheng Liu, Christopher I Amos, Qingyi Wei

Faculty, Staff and Students Publications

To identify genetic variants for risk of squamous cell carcinoma of the head and neck (SCCHN), we conducted a two-phase genome-wide association study consisting of 7,858,089 SNPs in 2,171 cases and 4,493 controls of non-Hispanic white, of which 434,839 typed and 7,423,250 imputed SNPs as the discovery. SNPs with P <1×10–3 were further validated in the OncoArray study of oral and pharynx cancer (5,205 cases and 3,232 controls of European ancestry) from dbGaP. Meta-analysis of the discovery and replication studies identified one novel locus 6p22.1 (P = 2.96×10–9 for the leading rs259919) and two cancer susceptibility loci 6p21.32 (rs3135001, HLA-DQB1) and 6p21.33 (rs1265081, CCHCR1) associated with SCCHN risk. Further stratification by tumor site revealed four known cancer loci (5p15.33, 6p21.32, 6p21.33, and 2p23.1) associated with oral cavity cancer risk and oropharyngeal cancer risk, respectively. In addition, one novel locus 18q22.2 (P = 2.54×10–9 for the leading SNP rs142021700) was identified for hypo-pharynx and larynx cancer risk. For SNPs in those reported or novel loci, we also performed functional annotations by bioinformatics prediction and eQTL analysis. Collectively, our identification of four reported loci (2p23.1, 5p15.33, 6p21.32, and 6p21.33) and two novel loci (6p22.1 and 18q22.2) for SCCHN risk highlight the importance of HLA loci for oropharyngeal cancer risk, suggesting that immunologic mechanisms are implicated in the etiology of this subset of SCCHN.

Association Between Changes In Subjective And Objective Measures Of Mobility In People With Lower Limb Amputations After Inpatient Rehabilitation, Gabrielle Cieslak, Humberto Omana, Edward Madou, Courtney Frengopoulos, Ricardo Viana, Michael W Payne, Susan W. Hunter

Physical Therapy Publications

Functional recovery for people with lower limb amputations is quantified using objective or subjective measures of performance. In this brief report, the prospective relationship between objective and subjective mobility after rehabilitation was evaluated in people with lower limb amputations. Adults undergoing inpatient prosthetic rehabilitation for a first unilateral transtibial or transfemoral level lower limb amputation were recruited. Assessment times: discharge and 4-mo follow-up. Gait velocity and the L Test under single- and dual-task conditions measured objective mobility. The Prosthetic Evaluation Questionnaire (section 4 and question 5b) measured subjective mobility. Paired t tests and Pearson correlation analysis evaluated change over time …

Implications Of New Understandings Of Gliomas In Children And Adults With Nf1: Report Of A Consensus Conference, Roger J Packer, David H Gutmann, Et Al.

2020-Current year OA Pubs

Gliomas are the most common primary central nervous system tumors occurring in children and adults with neurofibromatosis type 1 (NF1). Over the past decade, discoveries of the molecular basis of low-grade gliomas (LGGs) have led to new approaches for diagnosis and treatments. However, these new understandings have not been fully applied to the management of NF1-associated gliomas. A consensus panel consisting of experts in NF1 and gliomas was convened to review the current molecular knowledge of NF1-associated low-grade "transformed" and high-grade gliomas; insights gained from mouse models of NF1-LGGs; challenges in diagnosing and treating older patients with NF1-associated gliomas; and …

Fri0547 The Effect Of Corrected Inflammation, Oxidative Stress And Endothelial Dysfunction On Fmd Levels In Patients With Selected Chronic Diseases: A Quasi-Experimental Study., Mahmut Ilker Yilmaz, Micol Romano, Mustafa Kemal Basarali, Abdelbaset Elzagallaai, Murat Karaman, Zeynep Demir, Muhammet Fatih Demir, Fatih Akcay, Melik Seyrek, Nuri Haksever, David Piskin, Rolando Cimaz, Michael Rieder, Erkan Demirkaya

Paediatrics Publications

While the pathophysiology of chronic disorders varies there are three basic mechanisms - inflammation, oxidative stress and endothelial dysfunction - that are common in many chronic diseases. However, the failure of these mechanisms to work synchronously can lead to morbidity complicating the course of many chronic diseases. We analyzed data of 178 patients from cohorts with selected chronic diseases in this quasi-experimental study. Endothelial dysfunction was determined by flow-mediated dilatation (FMD) and asymmetric dimethylarginine (ADMA) levels. Serum ADMA, high sensitive C-reactive protein (hs-CRP), serum PTX3, malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), glutathione peroxidase (GSH-Px) levels and FMD were studied in baseline …

Zooming-Out Covid-19: Virtual Clinical Experiences In An Emergency Medicine Clerkship., Shruti Chandra, Chaiya Laoteppitaks, Nina Mingioni, Dimitrios Papanagnou

Department of Emergency Medicine Faculty Papers

In the setting of the novel 2019 coronavirus (COVID‐19) pandemic, it has been challenging to provide medical students in the Emergency Medicine (EM) clerkship meaningful clinical experiences that would meet clinical course goals and objectives, as well as satisfy Liaison Committee for Medical Education (LCME) requirements. During the EM clerkship, students play an integral role in interviewing patients, formulating treatment plans, facilitating patient discharges, and counseling patients. Immediately available direct and indirect supervision are paramount to ensure student learning and safe patient care. The authors present a novel clinical educational experience for senior medical students in an EM clerkship that …

Covid-19 Preclinical Models: Human Angiotensin-Converting Enzyme 2 Transgenic Mice., Cathleen Lutz, Leigh Maher, Charles Lee, Wonyoung Kang

Faculty Research 2020

Coronavirus disease 2019 (COVID-19) is a declared pandemic that is spreading all over the world at a dreadfully fast rate. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the pathogen of COVID-19, infects the human body using angiotensin-converting enzyme 2 (ACE2) as a receptor identical to the severe acute respiratory syndrome (SARS) pandemic that occurred in 2002-2003. SARS-CoV-2 has a higher binding affinity to human ACE2 than to that of other species. Animal models that mimic the human disease are highly essential to develop therapeutics and vaccines against COVID-19. Here, we review transgenic mice that express human ACE2 in the airway and …

Aav-Crispr Gene Editing Is Negated By Pre-Existing Immunity To Cas9, Ang Li, Mark R Tanner, Ciaran M Lee, Ayrea E Hurley, Marco De Giorgi, Kelsey E Jarrett, Timothy H Davis, Alexandria M Doerfler, Gang Bao, Christine Beeton, William R Lagor

Faculty, Staff and Students Publications

Adeno-associated viral (AAV) vectors are a leading candidate for the delivery of CRISPR-Cas9 for therapeutic genome editing in vivo. However, AAV-based delivery involves persistent expression of the Cas9 nuclease, a bacterial protein. Recent studies indicate a high prevalence of neutralizing antibodies and T cells specific to the commonly used Cas9 orthologs from Streptococcus pyogenes (SpCas9) and Staphylococcus aureus (SaCas9) in humans. We tested in a mouse model whether pre-existing immunity to SaCas9 would pose a barrier to liver genome editing with AAV packaging CRISPR-Cas9. Although efficient genome editing occurred in mouse liver with pre-existing SaCas9 immunity, this was accompanied by …

The Effect Of Corrected Inflammation, Oxidative Stress And Endothelial Dysfunction On Fmd Levels In Patients With Selected Chronic Diseases: A Quasi-Experimental Study., Mahmut Ilker Yilmaz, Micol Romano, Mustafa Kemal Basarali, Abdelbaset Elzagallaai, Murat Karaman, Zeynep Demir, Muhammet Fatih Demir, Fatih Akcay, Melik Seyrek, Nuri Haksever, David Piskin, Rolando Cimaz, Michael Rieder, Erkan Demirkaya

Paediatrics Publications

While the pathophysiology of chronic disorders varies there are three basic mechanisms - inflammation, oxidative stress and endothelial dysfunction - that are common in many chronic diseases. However, the failure of these mechanisms to work synchronously can lead to morbidity complicating the course of many chronic diseases. We analyzed data of 178 patients from cohorts with selected chronic diseases in this quasi-experimental study. Endothelial dysfunction was determined by flow-mediated dilatation (FMD) and asymmetric dimethylarginine (ADMA) levels. Serum ADMA, high sensitive C-reactive protein (hs-CRP), serum PTX3, malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), glutathione peroxidase (GSH-Px) levels and FMD were studied in baseline …

Ccdc61/Vfl3 Is A Paralog Of Sas6 And Promotes Ciliary Functions, Takashi Ochi, Huawen Lin, Susan K Dutcher, Et Al.

2020-Current year OA Pubs

Centrioles are cylindrical assemblies whose peripheral microtubule array displays a 9-fold rotational symmetry that is established by the scaffolding protein SAS6. Centriole symmetry can be broken by centriole-associated structures, such as the striated fibers in Chlamydomonas that are important for ciliary function. The conserved protein CCDC61/VFL3 is involved in this process, but its exact role is unclear. Here, we show that CCDC61 is a paralog of SAS6. Crystal structures of CCDC61 demonstrate that it contains two homodimerization interfaces that are similar to those found in SAS6, but result in the formation of linear filaments rather than rings. Furthermore, we show …

Evaluation Of Mavacamten In Symptomatic Patients With Nonobstructive Hypertrophic Cardiomyopathy, Carolyn Y Ho, Richard G Bach, Et Al.

2020-Current year OA Pubs

BACKGROUND: Patients with nonobstructive hypertrophic cardiomyopathy (nHCM) often experience a high burden of symptoms; however, there are no proven pharmacological therapies. By altering the contractile mechanics of the cardiomyocyte, myosin inhibitors have the potential to modify pathophysiology and improve symptoms associated with HCM.

OBJECTIVES: MAVERICK-HCM (Mavacamten in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy) explored the safety and efficacy of mavacamten, a first-in-class reversible inhibitor of cardiac-specific myosin, in nHCM.

METHODS: The MAVERICK-HCM trial was a multicenter, double-blind, placebo-controlled, dose-ranging phase II study in adults with symptomatic nHCM (New York Heart Association functional class II/III), left ventricular ejection fraction (LVEF) ≥55%, …

When Will I Get My Paper Back? A Replication Study Of Publication Timelines For Health Professions Education Research., Lauren A Maggio, William E Bynum, Deanna N Schreiber-Gregory, Steven J Durning, Anthony R. Artino

Health, Human Function, and Rehabilitation Sciences Faculty Publications

INTRODUCTION: Biomedical researchers have lamented the lengthy timelines from manuscript submission to publication and highlighted potential detrimental effects on scientific progress and scientists' careers. In 2015, Himmelstein identified the mean time from manuscript submission to acceptance in biomedicine as approximately 100 days. The length of publication timelines in health professions education (HPE) is currently unknown.

METHODS: This study replicates Himmelstein's work with a sample of 14 HPE journals published between 2008-2018. Using PubMed, 19,182 article citations were retrieved. Open metadata for each were downloaded, including the date the article was received by the journal, date the authors resubmitted revisions, date …

Innovative Virtual Mentoring Using The Extension For Community Healthcare Outcomes Model For Primary Care Providers For The Management Of Alcohol Use Disorders., Jayant Mahadevan, Lekhansh Shukla, Prabhat Kumar Chand, Miriam Komaromy, Pratima Murthy, Sanjeev Arora

Project ECHO Bibliography

The number of experts available for the management of alcohol use disorders (AUDs) in rural and underserved areas in India is limited. In this study, a blended training programme was conducted for 26 primary care providers (PCPs) from nine districts of Bihar, in best practices for the management of AUDs. A two weeks on-site training was followed by fortnightly online tele-Extension for Community Healthcare Outcomes (ECHO) clinics for six months using the 'Hub and Spokes' ECHO model, accessible through internet-enabled smartphones. A questionnaire administered at baseline and after six months assessed changes in the PCPs compliance with principles of AUD …

Prevalence And Clinical Features Of Inflammatory Bowel Diseases Associated With Monogenic Variants, Identified By Whole-Exome Sequencing In 1000 Children At A Single Center, Eileen Crowley, Neil Warner, Jie Pan, Sam Khalouei, Abdul Elkadri, Karoline Fiedler, Justin Foong, Andrei L Turinsky, Dana Bronte-Tinkew, Shiqi Zhang

Paediatrics Publications

BACKGROUND & AIMS: A proportion of infants and young children with inflammatory bowel diseases (IBDs) have subtypes associated with a single gene variant (monogenic IBD). We aimed to determine the prevalence of monogenic disease in a cohort of pediatric patients with IBD.

METHODS: We performed whole-exome sequencing analyses of blood samples from an unselected cohort of 1005 children with IBD, aged 0-18 years (median age at diagnosis, 11.96 years) at a single center in Canada and their family members (2305 samples total). Variants believed to cause IBD were validated using Sanger sequencing. Biopsies from patients were analyzed by immunofluorescence and …

Randomized Controlled Trial Of A Multilevel Intervention To Address Social Determinants Of Refugee Mental Health, Jessica R. Goodkind, Deborah Bybee, Julia Meredith Hess, Suha Amer, Martin Ndayisenga, R Neil Greene, Ryeora Choe, Brian Isakson, Brandon Baca, Mahbooba Pannah

Pediatrics Research and Scholarship

Understanding processes that support the well-being of the unprecedented numbers of forcibly displaced people throughout the world is essential. Growing evidence documents post-migration stressors related to marginalization as key social determinants of refugee mental health. The goal of this RCT was to rigorously test a social justice approach to reducing high rates of distress among refugees in the United States. The 6-month multilevel, strengths-based Refugee Well-being Project (RWP) intervention brought together university students enrolled in a 2-semester course and recently resettled refugees to engage in mutual learning and collaborative efforts to mobilize community resources and improve community and systems responsiveness …

Does Empathy Decline In The Clinical Phase Of Medical Education? A Nationwide, Multi-Institutional, Cross-Sectional Study Of Students At Do-Granting Medical Schools, Mohammadreza Hojat, Stephen C. Shannon, Jennifer Desantis, Mark R. Speicher, Lynn Bragan, Leonard H. Calabrese

CRMEHC Faculty Papers

PURPOSE: To examine differences in students' empathy in different years of medical school in a nationwide study of students of U.S. DO-granting medical schools.

METHOD: Participants in this cross-sectional study included 10,751 students enrolled in 41 of 48 campuses of DO-granting medical schools in the United States (3,616 first-year, 2,764 second-year, 2,413 third-year, and 1,958 fourth-year students). They completed a web-based survey at the end of the 2017-2018 academic year that included the Jefferson Scale of Empathy and the Infrequency Scale of the Zuckerman-Kuhlman Personality Questionnaire for measuring "good impression" response bias. Comparisons were made on empathy scores among students …

Viscoelastic Testing In Covid-19: A Possible Screening Tool For Severe Disease, Jay S. Raval, Allison E. Burnett, Marian A. Rollins-Raval, Joseph R. Griggs, Lizabeth Rosenbaum, Nathan D. Nielsen, Michelle S. Harkins

Pathology Research and Scholarship

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) that manifests with variable severity. 1 A subset of symptomatic individuals develop proinflammatory or prothrombotic profiles requiring additional testing and interventions. 2-5 It is unclear which COVID-19 patients will ultimately develop severe disease that would have benefitted from early and aggressive interventions.

Age-Adjusted D-Dimer Cutoffs: A Warning From The Laboratory, Marian A. Rollins-Raval, Richard A. Marlar, Andrew J. Goodwin

Pathology Research and Scholarship

D-dimer assays have been Food and Drug Administration (FDA)–approved or cleared for results below a manufacturer-defined cutoff in conjunction with low or intermediate pretest clinical probability to rule out venous thromboembolism.¹ Given apparent overall increase of D-dimer level with age, clinical guidelines have recommended application of an age-adjusted D-dimer–level cutoff to exclude suspected pulmonary embolus specifically in patients with low or intermediate pretest clinical probability.^2,3 Despite additional studies and literature availble, these guidelines themselves rest solely on the Age-Adjusted D-Dimer Cutoff Levels to Rule Out Pulmonary Embolism: The ADJUST-PE Study,⁴ applying an age-adjusted D-dimer–level …

Traumatic Injury Results In Prolonged Circulation Of Ultralarge Von Willebrand Factor And A Reduction In Adamts13 Activity, Mitchell R. Dyer, William E. Plautz, Margaret V. Ragni, Wyeth Alexander, Shannon Haldeman, Jason L. Sperry, Francis X. Guyette, Brian S. Zuckerbraun, Marian A. Rollins-Raval, Jay S. Raval, Matthew D. Neal

Pathology Research and Scholarship

BACKGROUND: Increases in plasma von Willebrand Factor (VWF) levels, accompanied by decreases in the metalloprotease ADAMTS13, have been demonstrated soon after traumatic injury while downstream effects remain unclear.

STUDY DESIGN AND METHODS: A cohort of 37 injured trauma patients from a randomized control trial investigating the use of prehospital plasma transfusion were analyzed for activity and antigen levels of ADAMTS13 and VWF at 0 and 24 hours after admission. Relevant clinical data were abstracted from the medical records. Trauma patient plasma was analyzed via agarose gel electrophoresis to evaluate the effects of injury on VWF multimer composition compared to healthy …

Relationships Of P16 Immunohistochemistry And Other Biomarkers With Diagnoses Of Cervical Abnormalities: Implications For Last Terminology, Philip E. Castle, Rachael Adcock, Jack Cuzick, Nicolas Wentzensen, Norah E. Torrez-Martinez, Salina M. Torres, Mark H. Stoler, Brigitte M. Ronnett, Nancy E. Joste, Teresa M. Darragh, Patti E. Gravitt, Mark Schiffman, William C. Hunt, Walter K. Kinney, Cosette M. Wheeler

Pathology Research and Scholarship

CONTEXT.—: Lower Anogenital Squamous Terminology (LAST) standardization recommended p16

OBJECTIVE.—: To describe the relationships of p16 IHC and other biomarkers associated with cervical cancer risk with biopsy diagnoses.

DESIGN.—: A statewide, stratified sample of cervical biopsies diagnosed by community pathologists (CPs), including 1512 CIN2, underwent a consensus, expert pathologist panel (EP) review (without p16 IHC results), p16 IHC interpretation by a third pathology group, and human papillomavirus (HPV) genotyping, results of which were grouped hierarchically according to cancer risk. Antecedent cytologic interpretations were also available.

RESULTS.—: Biopsies were more likely to test p16 IHC positive with increasing severity of CP …

Secukinumab Provides Sustained Low Rates Of Radiographic Progression In Psoriatic Arthritis: 52-Week Results From A Phase 3 Study, Future 5., Désirée Van Der Heijde, Philip Mease, Robert B M Landewé, Proton Rahman, Hasan Tahir, Atul Singhal, Elke Boettcher, Sandra Navarra, Xuan Zhu, Gregory Ligozio, Aimee Readie, Shephard Mpofu, Luminita Pricop

Articles, Abstracts, and Reports

OBJECTIVE: To evaluate the effect of secukinumab on radiographic progression through 52 weeks in patients with PsA from the FUTURE 5 study.

METHODS: Patients with active PsA, stratified by prior anti-TNF use (naïve or inadequate response), were randomized to s.c. secukinumab 300 mg load (300 mg), 150 mg load (150 mg), 150 mg no load regimens or placebo at baseline, at weeks 1, 2 and 3 and every 4 weeks starting at week 4. Radiographic progression was assessed by change in van der Heijde-modified total Sharp score (vdH-mTSS; mean of two readers). Statistical analysis used a linear mixed-effects model (random …

Potent, Specific Mepicides For Treatment Of Zoonotic Staphylococci, Rachel L. Edwards, Isabel Heueck, Soon Goo Lee, Ishaan T. Shah, Justin J. Miller, Andrew J. Jezewski, Marwa O. Mikati, Xu Wang, Robert C. Brothers, Kenneth M. Heidel, Damon M. Osbourn, Carey-Ann D. Burnham, Sophie Alvarez, Stephanie A. Fritz, Cynthia S. Dowd, Joseph M. Jez, Audrey R. Odom John

Open Access Publications

Coagulase-positive staphylococci, which frequently colonize the mucosal surfaces of animals, also cause a spectrum of opportunistic infections including skin and soft tissue infections, urinary tract infections, pneumonia, and bacteremia. However, recent advances in bacterial identification have revealed that these common veterinary pathogens are in fact zoonoses that cause serious infections in human patients. The global spread of multidrug-resistant zoonotic staphylococci, in particular the emergence of methicillin-resistant organisms, is now a serious threat to both animal and human welfare. Accordingly, new therapeutic targets that can be exploited to combat staphylococcal infections are urgently needed. Enzymes of the methylerythritol phosphate pathway (MEP) …

Wolff-Parkinson-White Syndrome: De Novo Variants And Evidence For Mutational Burden In Genes Associated With Atrial Fibrillation, Zeynep H Coban-Akdemir, Wu-Lin Charng, Mahshid Azamian, Ingrid S Paine, Jaya Punetha, Christopher M Grochowski, Tomasz Gambin, Santiago O Valdes, Bryan Cannon, Gladys Zapata, Patricia P Hernandez, Shalini Jhangiani, Harsha Doddapaneni, Jianhong Hu, Fatima Boricha, Donna M Muzny, Eric Boerwinkle, Yaping Yang, Richard A Gibbs, Jennifer E Posey, Xander H T Wehrens, John W Belmont, Jeffrey J Kim, Christina Y Miyake, James R Lupski, Seema R Lalani

Faculty, Staff and Student Publications

BACKGROUND: Wolff-Parkinson-White (WPW) syndrome is a relatively common arrhythmia affecting ~1-3/1,000 individuals. Mutations in PRKAG2 have been described in rare patients in association with cardiomyopathy. However, the genetic basis of WPW in individuals with a structurally normal heart remains poorly understood. Sudden death due to atrial fibrillation (AF) can also occur in these individuals. Several studies have indicated that despite ablation of an accessory pathway, the risk of AF remains high in patients compared to general population.

METHODS: We applied exome sequencing in 305 subjects, including 65 trios, 80 singletons, and 6 multiple affected families. We used de novo analysis, …

Prediction Of Trimethoprim/Sulfamethoxazole Resistance In Community-Onset Urinary Tract Infections, Madeline Demarsh, P Brandon Bookstaver, Caroline Gordon, Juanne Lim, Nicole Griffith, Nicole K. Bookstaver, Julie Ann Justo, Joseph Kohn, Majdi N. Al-Hasan

Faculty Publications

OBJECTIVES: This study aimed to predict trimethoprim/sulfamethoxazole (SXT) resistance in patients with community-onset urinary tract infection (UTI) due to Enterobacteriaceae based on patient-specific risk factors. METHODS: This was a retrospective case-control study in Prisma Health facilities in central South Carolina, USA, including three community hospitals, affiliated emergency departments and ambulatory clinics, including adult patients with community-onset UTI due to Enterobacteriaceae (1 April 2015 to 29 February 2016). Multivariate logistic regression was used to examine risk factors for SXT resistance. RESULTS: Among 351 unique patients with community-onset UTI, 71 (20.2%) had SXT-resistant Enterobacteriaceae urinary isolates. Overall, median age was 64 years …

A Smartphone Based E-Consult In Addiction Medicine: An Initiative In Covid Lockdown., Aurobind Ganesh, Prashant Sahu, Shruti Nair, Prabhat Chand

Project ECHO Bibliography

No abstract provided.

Elagolix Treatment For Up To 12 Months In Women With Heavy Menstrual Bleeding And Uterine Leiomyomas, James A Simon, Ayman Al-Hendy, David F Archer, Kurt T Barnhart, Linda D Bradley, Bruce R Carr, Thomas Dayspring, Eve C Feinberg, Veronica Gillispie, Sandra Hurtado, Jinhee Kim, Ran Liu, Charlotte D Owens, Ozgul Muneyyirci-Delale, Alice Wang, Nelson B Watts, William Schlaff

Department of Obstetrics and Gynecology Faculty Papers

Objective: To investigate the safety and efficacy of elagolix, an oral gonadotropin-releasing hormone antagonist, with hormonal add-back therapy for up to 12 months in women with heavy menstrual bleeding associated with uterine leiomyomas.

Methods: Elaris UF-EXTEND was a phase 3 extension study that evaluated an additional 6 months (up to 12 months total) of elagolix 300 mg twice daily with hormonal add-back therapy (estradiol 1 mg and norethindrone acetate 0.5 mg once daily) in women who completed an initial 6 months of the same treatment in one of two preceding phase 3 studies. The primary endpoint was the percentage of …

The Wrinkling Of Time: Aging, Inflammation, Oxidative Stress, And The Circadian Clock In Neurodegeneration, Brian V Lananna, Erik S Musiek

2020-Current year OA Pubs

A substantial body of research now implicates the circadian clock in the regulation of an array of diverse biological processes including glial function, metabolism, peripheral immune responses, and redox homeostasis. Sleep abnormalities and other forms of circadian disruption are common symptoms of aging and neurodegeneration. Circadian clock disruption may also influence the aging processes and the pathogenesis of neurodegenerative diseases. The specific mechanisms governing the interaction between circadian systems, aging, and the immune system are still being uncovered. Here, we review the evidence supporting a bidirectional relationship between aging and the circadian system. Further, we explore the hypothesis that age-related …