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Rate Of Surgery And Baseline Characteristics Associated With Surgery Progression In Young Athletes With Prearthritic Hip Disorders, Reid W Collis, Andrea B Mccullough, Chris Ng, Heidi Prather, Graham A Colditz, John C Clohisy, Abby L Cheng

Open Access Publications

Background: Prearthritic hip disorders (PAHD), such as femoroacetabular impingement (FAI), acetabular dysplasia, and acetabular labral tears, are a common cause of pain and dysfunction in adolescent and young adult athletes, and optimal patient-specific treatment has not been defined. Operative management is often recommended, but conservative management may be a reasonable approach for some athletes.

Purpose: To identify (1) the relative rate of progression to surgery in self-reported competitive athletes versus nonathletes with PAHD and (2) baseline demographic, pain, and functional differences between athletes who proceeded versus those who did not proceed to surgery within 1 year of evaluation.

Study Design: …

Pathways To Post-Traumatic Stress Disorder And Alcohol Dependence: Trauma, Executive Functioning, And Family History Of Alcoholism In Adolescents And Young Adults, Stacey Subbie-Saenz De Viteri, Andrey Anokhin, Vivia Mccutcheon, Kathleen Bucholz, Et Al

Open Access Publications

INTRODUCTION: Family history (FH) of alcohol dependence is likely to increase the risk of trauma exposure, post-traumatic stress disorder (PTSD), and alcohol dependence. FH of alcohol dependence and trauma has been separately shown to adversely affect planning/problem-solving aspects of executive function. However, few studies have examined these risk factors in an integrated model.

METHODS: Using data from trauma-exposed individuals from the Collaborative Study on the Genetics of Alcoholism prospective cohort (N = 1,860), comprising offspring from alcohol-dependent high-risk and comparison families (mean age [SE] = 21.9 [4.2]), we investigated associations of trauma (nonsexual assaultive, nonassaultive, sexual assaultive) with DSM-IV PTSD …

Beyond Just A Tight Fortress: Contribution Of Stroma To Epithelial-Mesenchymal Transition In Pancreatic Cancer, Ashenafi Bulle, Kian-Huat Lim

Open Access Publications

Novel effective treatment is direly needed for patients with pancreatic ductal adenocarcinoma (PDAC). Therapeutics that target the driver mutations, especially the KRAS oncoprotein and its effector cascades, have been ineffective. It is increasing clear that the extensive fibro-inflammatory stroma (or desmoplasia) of PDAC plays an active role in the progression and therapeutic resistance of PDAC. The desmoplastic stroma is composed of dense extracellular matrix (ECM) deposited mainly by the cancer-associated-fibroblasts (CAFs) and infiltrated with various types of immune cells. The dense ECM functions as a physical barrier that limits tumor vasculatures and distribution of therapeutics to PDAC cells. In addition, …

The Cost Of A Single Concussion In American High School Football: A Retrospective Cohort Study, Aaron M. Yengo-Kahn, Patrick D. Kelly, David C. Liles, Lydia J. Mckeithan, Candace J. Grisham, Muhammad Saad Khan, Timothy Lee, Andrew M. Kuhn, Christopher M. Bonfield, Scott L. Zuckerman

Open Access Publications

Aim: The potential financial burden of American football-related concussions (FRC) is unknown. Our objective was to describe the healthcare costs associated with an FRC and determine factors associated with increased costs.

Methodology/results: A retrospective cohort study of concussed high school football players presenting between November 2017 and March 2020 was undertaken; 144 male high school football players were included. Total costs were about $115,000, for an average direct healthcare cost of $800.10/concussion. Visiting the emergency department (β = 502.29, 95% CI: 105.79-898.61; p = 0.01), the initial post-concussion symptom scale score (β = 0.39, 95% CI: 0.11-0.66; p = 0.01) …

Sarm1 Depletion Rescues Nmnat1-Dependent Photoreceptor Cell Death And Retinal Degeneration, Yo Sasaki, Hiroki Kakita, Shunsuke Kubota, Abdoulaye Sene, Tae Jun Lee, Norimitsu Ban, Zhenyu Dong, Joseph B. Lin, Sanford L. Boye, Aaron Diantonio, Shannon E. Boye, Rajendra S. Apte, Jeffrey Milbrandt

Open Access Publications

Leber congenital amaurosis type nine is an autosomal recessive retinopathy caused by mutations of the NAD

Exome Sequencing Implicates Impaired Gaba Signaling And Neuronal Ion Transport In Trigeminal Neuralgia, Weilai Dong, Sheng Chih Jin, Et Al

Open Access Publications

Trigeminal neuralgia (TN) is a common, debilitating neuropathic face pain syndrome often resistant to therapy. The familial clustering of TN cases suggests that genetic factors play a role in disease pathogenesis. However, no unbiased, large-scale genomic study of TN has been performed to date. Analysis of 290 whole exome-sequenced TN probands, including 20 multiplex kindreds and 70 parent-offspring trios, revealed enrichment of rare, damaging variants in GABA receptor-binding genes in cases. Mice engineered with a TN-associated

Use And Awareness Of The Community Guide In State And Local Health Department Chronic Disease Programs, Emily Rodriguez Weno, Stephanie Mazzucca, Renee G Parks, Margaret Padek, Peg Allen, Ross C Brownson

Open Access Publications

INTRODUCTION: The Community Guide (Guide) is a user-friendly, systematic review system that provides information on evidence-based interventions (EBIs) in public health practice. Little is known about what predicts Guide awareness and use in state health departments (SHDs) and local health departments (LHDs).

METHODS: We pooled data from 3 surveys (administered in 2016, 2017, and 2018) to employees in chronic disease programs at SHDs and LHDs. Participants (n = 1,039) represented all 50 states. The surveys asked about department practices and individual, organizational, and external factors related to decisions about EBIs. We used χ

RESULTS: Eighty-one percent (n = 498) of …

Performance Of The Lateral Flow Assay And The Latex Agglutination Serum Cryptococcal Antigen Test In Cryptococcal Disease In Patients With And Without Hiv, Matthew A Hevey, Ige A George, Adriana M Rauseo, Lindsey Larson, William Powderly, Andrej Spec

Open Access Publications

Cryptococcal epidemiology is shifting toward HIV-negative populations who have diverse presentations. Cryptococcal antigen (CrAg) testing is also changing, with development of the lateral flow assay (LFA) having reported increased sensitivity and specificity, but with minimal knowledge in the HIV-negative population. In this study, we evaluate the real-life performance of CrAg testing in patients with cryptococcal disease. We conducted a retrospective review of patients with cryptococcosis from 2002 to 2019 at Barnes-Jewish Hospital. Latex agglutination (LA) was used exclusively until April 2016, at which point LFA was used exclusively. Demographics, presentations, and testing outcomes were evaluated. Serum CrAg testing was completed …

A Potential Role For Stress-Induced Microbial Alterations In Iga-Associated Irritable Bowel Syndrome With Diarrhea, Sunaina Rengarajan, Kathryn A Knoop, Arvind Rengarajan, Jiani N Chai, Jose G Grajales-Reyes, Vijay K Samineni, Emilie V Russler-Germain, Prabha Ranganathan, Alessio Fasano, Gregory S Sayuk, Robert W Gereau Iv, Andrew L Kau, Dan Knights, Purna C Kashyap, Matthew A Ciorba, Rodney D Newberry, Chyi-Song Hsieh

Open Access Publications

Stress is a known trigger for flares of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS); however, this process is not well understood. Here, we find that restraint stress in mice leads to signs of diarrhea, fecal dysbiosis, and a barrier defect via the opening of goblet-cell associated passages. Notably, stress increases host immunity to gut bacteria as assessed by immunoglobulin A (IgA)-bound gut bacteria. Stress-induced microbial changes are necessary and sufficient to elicit these effects. Moreover, similar to mice, many diarrhea-predominant IBS (IBS-D) patients from two cohorts display increased antibacterial immunity as assessed by IgA-bound fecal bacteria. This …

Role Of Endothelial Nitric Oxide Synthase In Isoflurane Conditioning-Induced Neurovascular Protection In Subarachnoid Hemorrhage, Umeshkumar Athiraman, Keshav Jayaraman, Meizi Liu, Tusar Giri, Jane Yuan, Gregory J Zipfel

Open Access Publications

Background Delayed cerebral ischemia remains a common and profound risk factor for poor outcome after subarachnoid hemorrhage (SAH). The aim of our current study is to define the role of endothelial nitric oxide synthase (eNOS) in isoflurane conditioning-induced neurovascular protection after SAH. Methods and Results Ten- to 14-week-old male wild-type mice (C57BL/6) as controls and eNOS knockout male mice (strain # 002684) were obtained for the study. Animals underwent either sham surgery, SAH surgery, or SAH with isoflurane conditioning. Anesthetic post conditioning was performed with isoflurane 2% for 1 hour, 1 hour after SAH. Normothermia was maintained with the homeothermic …

Rapid Determination Of Nematode Cell And Organ Susceptibility To Toxic Treatments, Douglas P Jasmer, Bruce A Rosa, Rahul Tyagi, Makedonka Mitreva

Open Access Publications

In research focused on the intestine of parasitic nematodes, we recently identified small molecule inhibitors toxic to intestinal cells of larval Ascaris suum (nematode intestinal toxins/toxicants; "NITs"). Some NITs had anthelmintic activity across the phylogenetic diversity of the Nematoda. The whole-worm motility inhibition assay quantified anthelmintic activity, but worm responses to NITs in relation to pathology or affected molecular pathways was not acquired. In this study we extended this research to more comprehensively determine in whole larval A. suum the cells, organ systems, molecular targets, and potential cellular pathways involved in mechanisms of toxicity leading to cell death. The experimental …

Burst Mitofusin Activation Reverses Neuromuscular Dysfunction In Murine Cmt2a, Antonietta Franco, Xiawei Dang, Emily K. Walton, Joshua N. Ho, Barbara Zablocka, Cindy Ly, Timothy M. Miller, Robert H. Baloh, Michael E. Shy, Andrew S. Yoo, Gerald W. Dorn

Open Access Publications

Charcot-Marie-Tooth disease type 2A (CMT2A) is an untreatable childhood peripheral neuropathy caused by mutations of the mitochondrial fusion protein, mitofusin (MFN) 2. Here, pharmacological activation of endogenous normal mitofusins overcame dominant inhibitory effects of CMT2A mutants in reprogrammed human patient motor neurons, reversing hallmark mitochondrial stasis and fragmentation independent of causal

The Fgf8 Subfamily (Fgf8, Fgf17 And Fgf18) Is Required For Closure Of The Embryonic Ventral Body Wall, Michael Boylan, Matthew J Anderson, David M Ornitz, Mark Lewandoski

Open Access Publications

The closure of the embryonic ventral body wall in amniotes is an important morphogenetic event and is essential for life. Defects in human ventral wall closure are a major class of birth defect and a significant health burden. Despite this, very little is understood about how the ventral body wall is formed. Here, we show that fibroblast growth factor (FGF) ligands FGF8, FGF17 and FGF18 are essential for this process. Conditional mouse mutants for these genes display subtle migratory defects in the abdominal muscles of the ventral body wall and an enlarged umbilical ring, through which the internal organs are …

Walking School Bus Programs: Implementation Factors, Implementation Outcomes, And Student Outcomes, 2017-2018, Jordan A Carlson, Chelsea Steel, Carolina M Bejarano, Marshall T Beauchamp, Ann M Davis, James F Sallis, Jon Kerner, Ross Brownson, Sara Zimmerman

Open Access Publications

PURPOSE AND OBJECTIVES: Walking school bus programs increase children's physical activity through active travel to school; however, research to inform large-scale implementation of such programs is limited. We investigated contextual factors, implementation outcomes, and student outcomes in existing walking school bus programs in the United States and internationally.

INTERVENTION APPROACH: Walking school bus programs involve a group of children walking to school together with an adult leader. On the trip to school, these adults provide social support, address potential traffic and interpersonal safety, and serve as role models to the children while children increase their physical activity levels.

EVALUATION METHODS: …

Associations Between Multimodal Fitness Assessments And Rowing Ergometer Performance In Collegiate Female Athletes, Clifton J Holmes, Bjoern Hornikel, Katherine Sullivan, Michael V Fedewa

Open Access Publications

The purpose was to examine the association of critical power from a three-minute all-out row (CP

Covid-19-Associated Acute Kidney Injury: Consensus Report Of The 25th Acute Disease Quality Initiative (Adqi) Workgroup, Mitra K Nadim, Anitha Vijayan, Et Al

Open Access Publications

Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the …

Zanubrutinib Monotherapy For Patients With Treatment Naïve Chronic Lymphocytic Leukemia And 17p Deletion, Constantine S. Tam, Brad S. Kahl, Et Al

Open Access Publications

Patients with chronic lymphocytic leukemia or small lymphocytic lymphoma whose tumors carry deletion of chromosome 17p13.1 [del(17p)] have an unfavorable prognosis and respond poorly to standard chemoimmunotherapy. Zanubrutinib is a selective next-generation Bruton tyrosine kinase inhibitor. We evaluated the safety and efficacy of zanubrutinib 160 mg twice daily in treatment-naïve patients with del(17p) disease enrolled in a dedicated, nonrandomized cohort (Arm C) of the phase 3 SEQUOIA trial. A total of 109 patients (median age, 70 years; range, 42 - 86) with centrally confirmed del(17p) were enrolled and treated. After a median of 18.2 months (range, 5.0 - 26.3), seven …

Acute Kidney Injury Pathology And Pathophysiology: A Retrospective Review, Joseph P. Gaut, Helen Liapis

Open Access Publications

Acute kidney injury (AKI) is the clinical term used for decline or loss of renal function. It is associated with chronic kidney disease (CKD) and high morbidity and mortality. However, not all causes of AKI lead to severe consequences and some are reversible. The underlying pathology can be a guide for treatment and assessment of prognosis. The Kidney Disease: Improving Global Outcomes guidelines recommend that the cause of AKI should be identified if possible. Renal biopsy can distinguish specific AKI entities and assist in patient management. This review aims to show the pathology of AKI, including glomerular and tubular diseases.

Argonaut: A Web Platform For Collaborative Multi-Omic Data Visualization And Exploration, Dain R Brademan, Ian J Miller, Nicholas W Kwiecien, David J Pagliarini, Michael S Westphall, Joshua J Coon, Evgenia Shishkova

Open Access Publications

Researchers now generate large multi-omic datasets using increasingly mature mass spectrometry techniques at an astounding pace, facing new challenges of "Big Data" dissemination, visualization, and exploration. Conveniently, web-based data portals accommodate the complexity of multi-omic experiments and the many experts involved. However, developing these tailored companion resources requires programming expertise and knowledge of web server architecture-a substantial burden for most. Here, we describe Argonaut, a simple, code-free, and user-friendly platform for creating customizable, interactive data-hosting websites. Argonaut carries out real-time statistical analyses of the data, which it organizes into easily sharable projects. Collaborating researchers worldwide can explore the results, visualized …

A Prognostic Gene Expression Signature For Oropharyngeal Squamous Cell Carcinoma, Xinyi Liu, Ping Liu, Rebecca D Chernock, Krystle A Lang Kuhs, James S Lewis, Jingqin Luo, Hiram A Gay, Wade L Thorstad, Xiaowei Wang

Open Access Publications

BACKGROUND: Robust prognostic stratification of patients with oropharyngeal squamous cell carcinoma (OPSCC) is important for developing individualized treatment plans. This study was conducted to develop and validate a clinically feasible prognostic classifier based on transcriptome-wide gene expression profiles.

METHODS: Tumor tissues were collected from 208 OPSCC patients treated at Washington University in St. Louis and 130 OPSCC patients treated at Vanderbilt University, used for model training and validation, respectively. OPSCC patients (n = 70) from the TCGA cohort were also included for independent validation. Based on RNA-seq profiling data, Cox proportional hazards regression analysis was performed to identify genes associated …

Proceedings From The Fourth International Symposium On Sigma-2 Receptors: Role In Health And Disease, Nicholas J Izzo, Martí Colom-Cadena, Aladdin A Riad, Jinbin Xu, Meharvan Singh, Carmen Abate, Michael A Cahill, Tara L Spires-Jones, Wayne D Bowen, Robert H Mach, Susan M Catalano

Open Access Publications

The sigma-2 receptor (S2R) complex has been implicated in central nervous system disorders ranging from anxiety and depression to neurodegenerative disorders such as Alzheimer's disease (AD). The proteins comprising the S2R complex impact processes including autophagy, cholesterol synthesis, progesterone signaling, lipid membrane-bound protein trafficking, and receptor stabilization at the cell surface. While there has been much progress in understanding the role of S2R in cellular processes and its potential therapeutic value, a great deal remains unknown. The

Delirium Prevention And Treatment In The Emergency Department (Ed): A Systematic Review Protocol, Elijah Blue Dahlstrom, Jin Ho Han, Heather Healy, Maura Kennedy, Glenn Arendts, Jacques Lee, Chris Carpenter, Sangil Lee

Open Access Publications

INTRODUCTION: Delirium is a dangerous syndrome of acute brain dysfunction that is common in the emergency department (ED), especially among the geriatric population. Most systematic reviews of interventions for delirium prevention and treatment have focused on inpatient settings. Best practices of effective delirium care in ED settings have not been established. The primary objective of this study is to identify pharmacologic and non-pharmacologic interventions as applied by physicians, nursing staff, pharmacists and other ED personnel to prevent incident delirium and to shorten the severity and duration of prevalent delirium in a geriatric population within the ED.

METHODS AND ANALYSIS: Searches …

Med19 Regulates Adipogenesis And Maintenance Of White Adipose Tissue Mass By Mediating Pparγ-Dependent Gene Expression, John M Dean, Anyuan He, Min Tan, Jun Wang, Dongliang Lu, Babak Razani, Irfan J Lodhi

Open Access Publications

The Mediator complex relays regulatory signals from gene-specific transcription factors to the basal transcriptional machinery. However, the role of individual Mediator subunits in different tissues remains unclear. Here, we demonstrate that MED19 is essential for adipogenesis and maintenance of white adipose tissue (WAT) by mediating peroxisome proliferator-activated receptor gamma (PPARγ) transcriptional activity. MED19 knockdown blocks white adipogenesis, but not brown adipogenesis or C2C12 myoblast differentiation. Adipose-specific MED19 knockout (KO) in mice results in a striking loss of WAT, whitening of brown fat, hepatic steatosis, and insulin resistance. Inducible adipose-specific MED19 KO in adult animals also results in lipodystrophy, demonstrating its …

Tgfβr-Smad3 Signaling Induces Resistance To Parp Inhibitors In The Bone Marrow Microenvironment, Bac Viet Le, Juo-Chin Yao, Grant A Challen, Daniel Link, Et Al

Open Access Publications

Synthetic lethality triggered by PARP inhibitor (PARPi) yields promising therapeutic results. Unfortunately, tumor cells acquire PARPi resistance, which is usually associated with the restoration of homologous recombination, loss of PARP1 expression, and/or loss of DNA double-strand break (DSB) end resection regulation. Here, we identify a constitutive mechanism of resistance to PARPi. We report that the bone marrow microenvironment (BMM) facilitates DSB repair activity in leukemia cells to protect them against PARPi-mediated synthetic lethality. This effect depends on the hypoxia-induced overexpression of transforming growth factor beta receptor (TGFβR) kinase on malignant cells, which is activated by bone marrow stromal cells-derived transforming …

Brown Adipose Expansion And Remission Of Glycemic Dysfunction In Obese Sm/J Mice, Caryn Carson, Juan F Macias-Velasco, Subhadra Gunawardana, Mario A Miranda, Sakura Oyama, Celine L St Pierre, Heather Schmidt, Jessica P Wayhart, Heather A Lawson

Open Access Publications

We leverage the SM/J mouse to understand glycemic control in obesity. High-fat-fed SM/J mice initially develop poor glucose homeostasis relative to controls. Strikingly, their glycemic dysfunction resolves by 30 weeks of age despite persistent obesity. The mice dramatically expand their brown adipose depots as they resolve glycemic dysfunction. This occurs naturally and spontaneously on a high-fat diet, with no temperature or genetic manipulation. Removal of the brown adipose depot impairs insulin sensitivity, indicating that the expanded tissue is functioning as an insulin-stimulated glucose sink. We describe morphological, physiological, and transcriptomic changes that occur during the brown adipose expansion and remission …

The Glycoprotease Cpaa Secreted By Medically Relevant Acinetobacter Species Targets Multiple O-Linked Host Glycoproteins, M Florencia Haurat, Nichollas E Scott, Gisela Di Venanzio, Juvenal Lopez, Benjamin Pluvinage, Alisdair B Boraston, Michael J Ferracane, Mario F Feldman

Open Access Publications

Glycans decorate proteins and affect their biological function, including protection against proteolytic degradation. However, pathogenic, and commensal bacteria have evolved specific glycoproteases that overcome the steric impediment posed by carbohydrates, cleaving glycoproteins precisely at their glycosylation site(s). Medically relevant

Isg15 Connects Autophagy And Ifn-Γ-Dependent Control Of Toxoplasma Gondii Infection In Human Cells, Jaya Bhushan, Joshua B Radke, Yi-Chieh Perng, Michael Mcallaster, Deborah J Lenschow, Herbert W Virgin, L David Sibley

Open Access Publications

The intracellular protozoan parasite

Alternative Splicing During The Chlamydomonas Reinhardtii Cell Cycle, Manishi Pandey, Gary D Stormo, Susan K Dutcher

Open Access Publications

Genome-wide analysis of transcriptome data in

A New Domestic Cat Genome Assembly Based On Long Sequence Reads Empowers Feline Genomic Medicine And Identifies A Novel Gene For Dwarfism, Reuben M. Buckley, Brian W. Davis, Wesley A. Brashear, Fabiana H. G. Farias, Kei Kuroki, Tina Graves, Ladeana W. Hillier, Milinn Kremitzki, Gang Li, Rondo P. Middleton, Patrick Minx, Chad Tomlinson, Leslie A. Lyons, William J. Murphy, Wesley C. Warren

Open Access Publications

The domestic cat (Felis catus) numbers over 94 million in the USA alone, occupies households as a companion animal, and, like humans, suffers from cancer and common and rare diseases. However, genome-wide sequence variant information is limited for this species. To empower trait analyses, a new cat genome reference assembly was developed from PacBio long sequence reads that significantly improve sequence representation and assembly contiguity. The whole genome sequences of 54 domestic cats were aligned to the reference to identify single nucleotide variants (SNVs) and structural variants (SVs). Across all cats, 16 SNVs predicted to have deleterious impacts and in …

Upper Extremity Pain And Overuse Injuries In Fly-Fishing: A North American Cross-Sectional Survey And Implications For Injury Prevention, Andrew W Kuhn, John E Kuhn

Open Access Publications

Background: Fly-fishing requires rhythmic, coordinated movements to successfully cast a fly line. Previous studies have shown that the biomechanical demands of fly-casting may cause some individuals to develop upper extremity pain or injuries.

Purpose: To report the rates, trends, and contributing factors of upper extremity pain and overuse injuries in a sample of North American recreational fly-fishers.

Study Design: Descriptive epidemiology study.

Methods: Participants were reached via 3 popular online fly-fishing forums in April 2019. Each consenting North American participant over 18 years of age was given a link to a unique survey that recorded his or her demographic and …