Medicine and Health Sciences Commons^™

Community Access To Primary Care Is An Important Geographic Disparity Among Ovarian Cancer Patients Undergoing Cytoreductive Surgery, Abigail S Zamorano, Angela L Mazul, Christine Marx, Mary M Mullen, Molly Greenwade, L Stewart Massad, Carolyn K Mccourt, Andrea R Hagemann, Premal H Thaker, Katherine C Fuh, Matthew A Powell, David G Mutch, Dineo Khabele, Lindsay M Kuroki

2020-Current year OA Pubs

OBJECTIVE: Given the importance of understanding neighborhood context and geographic access to care on individual health outcomes, we sought to investigate the association of community primary care (PC) access on postoperative outcomes and survival in ovarian cancer patients.

METHODS: This was a retrospective cohort study of Stage III-IV ovarian cancer patients who underwent surgery at a single academic, tertiary care hospital between 2012 and 2015. PC access was determined using a Health Resources and Services Administration designation. Outcomes included 30-day surgical and medical complications, extended hospital stay, ICU admission, hospital readmission, progression-free and overall survival. Descriptive statistics and chi-squared analyses …

Leflunomide-Induced And Paraneoplastic Ulcers In A Rheumatoid Arthritis Patient, Michael R Vittori, Jonathan Z Tang, William H Mccoy Iv

2020-Current year OA Pubs

No abstract provided.

Axillary Artery Fibromuscular Dysplasia In A Symptomatic Type B Aortic Dissection Causing Acute Limb Ischemia, Brian Sullivan, Nathan Droz, Vipul Khetarpaul

2020-Current year OA Pubs

Fibromuscular dysplasia (FMD) can manifest outside of its classic presentation with unusual pathology. In the present report, we have described a case of an older male patient with aortic degeneration related to acute type B dissection who had required emergent left carotid-subclavian transposition and aortic stenting. Intraoperatively, his axillary artery FMD led to acute upper extremity ischemia. The patient was treated with classic maneuvers, including balloon angioplasty, reflecting the best practices in vascular surgery. We have also discussed the diagnosis, classification, and management of FMD.

Prolonged Dexamethasone Exposure Enhances Zebrafish Lateral-Line Regeneration But Disrupts Mitochondrial Homeostasis And Hair Cell Function, Allison L Saettele, Hiu-Tung C Wong, Katie S Kindt, Mark E Warchol, Lavinia Sheets

2020-Current year OA Pubs

The synthetic glucocorticoid dexamethasone is commonly used to treat inner ear disorders. Previous work in larval zebrafish has shown that dexamethasone treatment enhances hair cell regeneration, yet dexamethasone has also been shown to inhibit regeneration of peripheral nerves after lesion. We therefore used the zebrafish model to determine the impact of dexamethasone treatment on lateral-line hair cells and primary afferents. To explore dexamethasone in the context of regeneration, we used copper sulfate (CuSO

Infections In The First Year Of Life And Development Of Beta Cell Autoimmunity And Clinical Type 1 Diabetes In High-Risk Individuals: The Trigr Cohort, Olga Kordonouri, David Cuthbertson, Malin Belteky, Bärbel Aschemeier-Fuchs, Neil H White, Elisabeth Cummings, Mikael Knip, Johnny Ludvigsson

2020-Current year OA Pubs

AIMS/HYPOTHESIS: Accumulated data suggest that infections in early life contribute to the development of type 1 diabetes. Using data from the Trial to Reduce IDDM in the Genetically at Risk (TRIGR), we set out to assess whether children who later developed diabetes-related autoantibodies and/or clinical type 1 diabetes had different exposure to infections early in life compared with those who did not.

METHODS: A cohort of 2159 children with an affected first-degree relative and HLA-conferred susceptibility to type 1 diabetes were recruited between 2002 and 2007 and followed until 2017. Infections were registered prospectively. The relationship between infections in the …

Practice Patterns Of Induction Therapy In Severe Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitis, Faten Aqeel, Lillian Xu, Ojaswi Tomar, Jessica Duchen, Tingting Li, Duvuru Geetha

2020-Current year OA Pubs

No abstract provided.

The Multifaceted Mechanisms Of Malignant Glioblastoma Progression And Clinical Implications, Rui Sun, Albert H Kim

2020-Current year OA Pubs

With the application of high throughput sequencing technologies at single-cell resolution, studies of the tumor microenvironment in glioblastoma, one of the most aggressive and invasive of all cancers, have revealed immense cellular and tissue heterogeneity. A unique extracellular scaffold system adapts to and supports progressive infiltration and migration of tumor cells, which is characterized by altered composition, effector delivery, and mechanical properties. The spatiotemporal interactions between malignant and immune cells generate an immunosuppressive microenvironment, contributing to the failure of effective anti-tumor immune attack. Among the heterogeneous tumor cell subpopulations of glioblastoma, glioma stem cells (GSCs), which exhibit tumorigenic properties and …

Defining Terms Commonly Used In Sarcopenia Research: A Glossary Proposed By The Global Leadership In Sarcopenia (Glis) Steering Committee, Peggy M Cawthon, Ellen Binder, Et Al.

2020-Current year OA Pubs

METHODS: The aim of this paper is to define terms commonly related to sarcopenia to enable standardization of these terms in research and clinical settings. The Global Leadership Initiative in Sarcopenia (GLIS) aims to bring together leading investigators in sarcopenia research to develop a single definition that can be utilized worldwide; work on a global definition of sarcopenia is ongoing. The first step of GLIS is to develop the common terminology, or a glossary, that will facilitate agreement on a global definition of sarcopenia as well as interpretation of clinical and research findings.

RESULTS: Several terms that are commonly used …

Macrophage Depletion Blocks Congenital Sarm1-Dependent Neuropathy, Caitlin B Dingwall, Amy Strickland, Sabrina W Yum, Aldrin Ky Yim, Jian Zhu, Peter L. Wang, Yurie Yamada, Robert E. Schmidt, Yo Sasaki, A. Joseph Bloom, Aaron Diantonio, Jeffrey Milbrandt

2020-Current year OA Pubs

Axon loss contributes to many common neurodegenerative disorders. In healthy axons, the axon survival factor NMNAT2 inhibits SARM1, the central executioner of programmed axon degeneration. We identified 2 rare NMNAT2 missense variants in 2 brothers afflicted with a progressive neuropathy syndrome. The polymorphisms resulted in amino acid substitutions V98M and R232Q, which reduced NMNAT2 NAD+-synthetase activity. We generated a mouse model to mirror the human syndrome and found that Nmnat2V98M/R232Q compound-heterozygous CRISPR mice survived to adulthood but developed progressive motor dysfunction, peripheral axon loss, and macrophage infiltration. These disease phenotypes were all SARM1-dependent. Remarkably, macrophage depletion therapy blocked and reversed …

A Sarm1-Mitochondrial Feedback Loop Drives Neuropathogenesis In A Charcot-Marie-Tooth Disease Type 2a Rat Model, Yurie Sato-Yamada, Amy Strickland, Yo Sasaki, Joseph Bloom, Aaron Diantonio, Jeffrey Milbrandt

2020-Current year OA Pubs

Charcot-Marie-Tooth disease type 2A (CMT2A) is an axonal neuropathy caused by mutations in the mitofusin 2 (MFN2) gene. MFN2 mutations result in profound mitochondrial abnormalities, but the mechanism underlying the axonal pathology is unknown. Sterile α and Toll/IL-1 receptor motif-containing 1 (SARM1), the central executioner of axon degeneration, can induce neuropathy and is activated by dysfunctional mitochondria. We tested the role of SARM1 in a rat model carrying a dominant CMT2A mutation (Mfn2H361Y) that exhibits progressive dying-back axonal degeneration, neuromuscular junction (NMJ) abnormalities, muscle atrophy, and mitochondrial abnormalities - all hallmarks of the human disease. We generated Sarm1-KO (Sarm1-/-) and …

Mild Hypoxic-Ischemic Encephalopathy (Hie): Timing And Pattern Of Mri Brain Injury, Yi Li, Jessica L Wisnowski, Lina Chalak, Amit M Mathur, Robert C Mckinstry, Genesis Licona, Dennis E Mayock, Taeun Chang, Krisa P Van Meurs, Tai-Wei Wu, Kaashif A Ahmad, Marie-Coralie Cornet, Rakesh Rao, Aaron Scheffler, Yvonne W Wu

2020-Current year OA Pubs

BACKGROUND: Mild hypoxic-ischemic encephalopathy (HIE) is increasingly recognized as a risk factor for neonatal brain injury. We examined the timing and pattern of brain injury in mild HIE.

METHODS: This retrospective cohort study includes infants with mild HIE treated at 9 hospitals. Neonatal brain MRIs were scored by 2 reviewers using a validated classification system, with discrepancies resolved by consensus. Severity and timing of MRI brain injury (i.e., acute, subacute, chronic) was scored on the subset of MRIs that were performed at or before 8 days of age.

RESULTS: Of 142 infants with mild HIE, 87 (61%) had injury on …

Gunshot Wound To The Spine With Delayed Radiculopathy: A Case Report, Kunj Patel, Rachita Navara, Faizal Ouedraogo, Ronald Joel, Brock Bowman

2020-Current year OA Pubs

Gunshot wounds (GSWs) to any part of the body can leave a trail of insidious complications. When the spinal cord is the injured organ, these sequelae can be debilitating to the patient and often exhaust all known therapeutic approaches available to the providers. The management of pain associated with GSWs to the spine is often a clinical challenge and there is often a question as to whether or not surgical intervention can help with pain relief in these cases. Here, we present a 45-year-old woman who experienced delayed radicular pain following a GSW to the spine with a retained bullet …

Cortical Bone Relationships Are Maintained Regardless Of Sex And Diet In A Large Population Of Lgxsm Advanced Intercross Mice, Nicole Migotsky, Michael D Brodt, James M Cheverud, Matthew J Silva

2020-Current year OA Pubs

INTRODUCTION: Knowledge of bone structure-function relationships in mice has been based on relatively small sample sets that limit generalizability. We sought to investigate structure-function relationships of long bones from a large population of genetically diverse mice. Therefore, we analyzed previously published data from the femur and radius of male and female mice from the F34 generation of the Large-by-Small advanced intercross line (LGXSM AI), which have over a two-fold continuous spread of bone and body sizes (Silva et al. 2019 JBMR).

METHODS: Morphological traits, mechanical properties, and estimated material properties were collected from the femur and radius from 1113 LGXSM …

Delayed Diagnosis And Recovery Of Fulminant Immune Checkpoint Inhibitor-Associated Myocarditis On Va-Ecmo Support, Tarun Ramayya, Joshua D Mitchell, Justin C Hartupee, Kory Lavine, Clare H Ridley, Kunal D Kotkar, Jesus Jimenez, Chieh-Yu Lin, Jose A Alvarez-Cardona, Ronald K Krone, Courtney M Campbell

2020-Current year OA Pubs

No abstract provided.

Targeting The Autophagy-Lysosome Pathway In A Pathophysiologically Relevant Murine Model Of Reversible Heart Failure, Sarah Evans, Xiucui Ma, Xiqiang Wang, Yana Chen, Chen Zhao, Carla J Weinheimer, Attila Kovacs, Brian Finck, Abhinav Diwan, Douglas L Mann

2020-Current year OA Pubs

The key biological "drivers" that are responsible for reverse left ventricle (LV) remodeling are not well understood. To gain an understanding of the role of the autophagy-lysosome pathway in reverse LV remodeling, we used a pathophysiologically relevant murine model of reversible heart failure, wherein pressure overload by transaortic constriction superimposed on acute coronary artery (myocardial infarction) ligation leads to a heart failure phenotype that is reversible by hemodynamic unloading. Here we show transaortic constriction + myocardial infarction leads to decreased flux through the autophagy-lysosome pathway with the accumulation of damaged proteins and organelles in cardiac myocytes, whereas hemodynamic unloading is …

Identification Of Patients With Ovarian Cancer Experiencing The Highest Benefit From Bevacizumab In The First-Line Setting On The Basis Of Their Tumor-Intrinsic Chemosensitivity (Kelim): The Gog-0218 Validation Study, Benoit You, David Mutch, Et Al.

2020-Current year OA Pubs

PURPOSE: In patients with high-grade ovarian cancer, predictors of bevacizumab efficacy in first-line setting are needed. In the ICON-7 trial, a poor tumor intrinsic chemosensitivity (defined by unfavorable modeled cancer antigen-125 [CA-125] ELIMination rate constant K [KELIM] score) was a predictive biomarker. Only the patients with high-risk disease (suboptimally resected stage III, or stage IV) exhibiting unfavorable KELIM score < 1.0 had overall survival (OS) benefit from bevacizumab (median: 29.7

METHODS: In GOG-0218, 1,873 patients were treated with carboplatin-paclitaxel ± concurrent-maintenance bevacizumab/placebo. Patient KELIM values were calculated with CA-125 kinetics during the first 100 chemotherapy days by the Lyon University team. The association between KELIM score (favorable ≥ 1.0, or unfavorable …

Benefits Of Early Treatment With Natalizumab: A Real-World Study, Daniel Ontaneda, Ellen M Mowry, Scott D Newsome, Robert T Naismith, Jacqueline Nicholas, Elizabeth Fisher, Carl De Moor, Justin Bohn, Pei-Ran Ho, Al Sandrock, Richard Rudick, James R Williams

2020-Current year OA Pubs

BACKGROUND: The impact of early versus later high-efficacy disease-modifying therapy (DMT) in patients with multiple sclerosis (MS) is uncertain. This study reported the association of early versus later natalizumab treatment with real-world clinical outcomes in MS patients.

METHODS: The study included 661 participants diagnosed with MS in 1994 or later from 7 US centers participating in the MS Partners Advancing Technology for Health Solutions (MS PATHS) network. Time to natalizumab treatment between diagnosis and first infusion (TTNT) was determined from the Tysabri Outreach: Unified Commitment to Health (TOUCH) registry. Clinical outcomes were defined using neuroperformance tests included in the Multiple …

The Clinical Spectrum Of Sma-Pme And In Vitro Normalization Of Its Cellular Ceramide Profile, Michelle M Lee, Toni S Pearson, Et Al.

2020-Current year OA Pubs

OBJECTIVE: The objectives of this study were to define the clinical and biochemical spectrum of spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) and to determine if aberrant cellular ceramide accumulation could be normalized by enzyme replacement.

METHODS: Clinical features of 6 patients with SMA-PME were assessed by retrospective chart review, and a literature review of 24 previously published cases was performed. Leukocyte enzyme activity of acid ceramidase was assessed with a fluorescence-based assay. Skin fibroblast ceramide content and was assessed by high performance liquid chromatography, electrospray ionization tandem mass spectroscopy. Enzyme replacement was assessed using recombinant human acid ceramidase …

Diptoindonesin G Is A Middle Domain Hsp90 Modulator For Cancer Treatment, Kristine Donahue, Haibo Xie, Miyang Li, Ang Gao, Min Ma, Yidan Wang, Rose Tipton, Nicole Semanik, Tina Primeau, Shunqiang Li, Lingjun Li, Weiping Tang, Wei Xu

2020-Current year OA Pubs

HSP90 inhibitors can target many oncoproteins simultaneously, but none have made it through clinical trials due to dose-limiting toxicity and induction of heat shock response, leading to clinical resistance. We identified diptoindonesin G (dip G) as an HSP90 modulator that can promote degradation of HSP90 clients by binding to the middle domain of HSP90 (K

Basal Bodies Bend In Response To Ciliary Forces, Anthony D Junker, Louis G Woodhams, Adam W J Soh, Eileen T O'Toole, Philip V Bayly, Chad G Pearson

2020-Current year OA Pubs

Motile cilia beat with an asymmetric waveform consisting of a power stroke that generates a propulsive force and a recovery stroke that returns the cilium back to the start. Cilia are anchored to the cell cortex by basal bodies (BBs) that are directly coupled to the ciliary doublet microtubules (MTs). We find that, consistent with ciliary forces imposing on BBs, bending patterns in BB triplet MTs are responsive to ciliary beating. BB bending varies as environmental conditions change the ciliary waveform. Bending occurs where striated fibers (SFs) attach to BBs and mutants with short SFs that fail to connect to …

Comparing Antigenaemia- And Microfilaraemia As Criteria For Stopping Decisions In Lymphatic Filariasis Elimination Programmes In Africa, Wilma A. Stolk, Luc E. Coffeng, Fatorma K. Bolay, Obiora A. Eneanya, Peter U. Fischer, T. Déirdre Hollingsworth, Benjamin G. Koudou, Aboulaye Méité, Edwin Michael, Joaquin M. Prada, Rocio M. Caja Rivera, Swarnali Sharma, Panayiota Touloupou, Gary J. Weil, Sake J. De Vlas

2020-Current year OA Pubs

BACKGROUND: Mass drug administration (MDA) is the main strategy towards lymphatic filariasis (LF) elimination. Progress is monitored by assessing microfilaraemia (Mf) or circulating filarial antigenaemia (CFA) prevalence, the latter being more practical for field surveys. The current criterion for stopping MDA requires <2% CFA prevalence in 6- to 7-year olds, but this criterion is not evidence-based. We used mathematical modelling to investigate the validity of different thresholds regarding testing method and age group for African MDA programmes using ivermectin plus albendazole.

METHODOLGY/PRINCIPAL FINDINGS: We verified that our model captures observed patterns in Mf and CFA prevalence during annual MDA, assuming that CFA tests are positive if at least one adult worm is present. We then assessed how well elimination can be predicted from CFA prevalence in 6-7-year-old children or from Mf or CFA prevalence in the 5+ or 15+ …

Ten Simple Rules And A Template For Creating Workflows-As-Applications, Michael J. Roach, N. Tessa Pierce-Ward, Radoslaw Suchecki, Vijini Mallawaarachchi, Bhavya Papudeshi, Scott A. Handley, C. Titus Brown, Nathan S. Watson-Haigh, Robert A. Edwards

2020-Current year OA Pubs

No abstract provided.

Whole-Genome And Long-Read Sequencing Identify A Novel Mechanism In Rfc1 Resulting In Canvas Syndrome, Katherine Abell King, Daniel J. Wegner, Robert C. Bucelli, Jessica Shapiro, Alexander J. Paul, Patricia I. Dickson, Jennifer A. Wambach, Undiagnosed Disease Network

2020-Current year OA Pubs

OBJECTIVES: Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) results from biallelic intronic pentanucleotide repeats in

METHODS: We performed whole-genome sequencing (WGS) on peripheral blood DNA samples from the proband and his unaffected mother. We performed DNA long-read sequencing and synthesized complementary DNA from RNA using peripheral blood from the proband.

RESULTS: WGS confirmed the maternally inherited

DISCUSSION: We report an adult with CANVAS due to compound heterozygous pathogenic

Differential Roles Of Aβ42/40, P-Tau231 And P-Tau217 For Alzheimer's Trial Selection And Disease Monitoring, Nicholas J Ashton, Yan Li, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Blood biomarkers indicative of Alzheimer's disease (AD) pathology are altered in both preclinical and symptomatic stages of the disease. Distinctive biomarkers may be optimal for the identification of AD pathology or monitoring of disease progression. Blood biomarkers that correlate with changes in cognition and atrophy during the course of the disease could be used in clinical trials to identify successful interventions and thereby accelerate the development of efficient therapies. When disease-modifying treatments become approved for use, efficient blood-based biomarkers might also inform on treatment implementation and management in clinical practice. In the BioFINDER-1 cohort, plasma phosphorylated (p)-tau231 and amyloid-β42/40 ratio …

Transferability Of Alzheimer Disease Polygenic Risk Score Across Populations And Its Association With Alzheimer Disease-Related Phenotypes, Sang-Hyuk Jung, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Polygenic risk scores (PRSs), which aggregate the genetic effects of single-nucleotide variants identified in genome-wide association studies (GWASs), can help distinguish individuals at a high genetic risk for Alzheimer disease (AD). However, genetic studies have predominantly focused on populations of European ancestry.

OBJECTIVE: To evaluate the transferability of a PRS for AD in the Korean population using summary statistics from a prior GWAS of European populations.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study developed a PRS based on the summary statistics of a large-scale GWAS of a European population (the International Genomics of Alzheimer Project; 21 982 AD cases …

Opensep: A Generalizable Open Source Pipeline For Sofa Score Calculation And Sepsis-3 Classification, Mackenzie R Hofford, Sean C Yu, Alistair E W Johnson, Albert M Lai, Philip R O Payne, Andrew P Michelson

2020-Current year OA Pubs

EHR-based sepsis research often uses heterogeneous definitions of sepsis leading to poor generalizability and difficulty in comparing studies to each other. We have developed OpenSep, an open-source pipeline for sepsis phenotyping according to the Sepsis-3 definition, as well as determination of time of sepsis onset and SOFA scores. The Minimal Sepsis Data Model was developed alongside the pipeline to enable the execution of the pipeline to diverse sources of electronic health record data. The pipeline's accuracy was validated by applying it to the MIMIC-IV version 1.0 data and comparing sepsis onset and SOFA scores to those produced by the pipeline …

Glycemia And Β-Cell Function Before And After Elexacaftor/Tezacaftor/Ivacaftor In Youth And Adults With Cystic Fibrosis, Christine L Chan, Andrea Granados, Amir Moheet, Sachinkumar Singh, Timothy Vigers, Ana Maria Arbeláez, Yaling Yi, Shanming Hu, Andrew W Norris, Katie Larson Ode

2020-Current year OA Pubs

BACKGROUND: Diabetes is prevalent among people with CF (PwCF) and associated with worse clinical outcomes. CFTR modulators are highly effective in improving the disease course of CF. However, the effects of elexacaftor/tezacaftor/ivacaftor (ETI) on glucose metabolism in PwCF are unclear.

METHODS: Twenty youth and adults with CF underwent frequently sampled oral glucose tolerance tests (fsOGTT) before and after ETI initiation. Glucose, insulin, and C-peptide were collected at 0, 10, 30, 60, 90, and 120 min after 1.75 g/kg (max 75 g) of dextrose. HbA1c and continuous glucose monitoring (CGM) were collected in a subset. Estimates of insulin secretion (C-peptide index), …

Law Library Blog (December 2022): Legal Beagle's Blog Archive, Roger Williams University School Of Law

Law Library Newsletters/Blog

No abstract provided.

Changes In Practice/Outcomes Of Pediatric/Congenital Catheterization In Response To The First Wave Of Covid, Brian Quinn, Andrew C Glatz, Et Al.

2020-Current year OA Pubs

BACKGROUND: The COVID-19 pandemic has posed tremendous stress on the health care system. Its effects on pediatric/congenital catheterization program practice and performance have not been described.

OBJECTIVES: The purpose of this study was to evaluate how case volumes, risk-profile, and outcomes of pediatric/congenital catheterization procedures changed in response to the first wave of COVID-19 and after that wave.

METHODS: A multicenter retrospective observational study was performed using Congenital Cardiac Catheterization Project on Outcomes Registry (C3PO) data to study changes in volume, case mix, and outcomes (high-severity adverse events [HSAEs]) during the first wave of COVID (March 1, 2020, to May …

Listeria Motility Increases The Efficiency Of Epithelial Invasion During Intestinal Infection, Inge M. N. Wortel, Seonyoung Kim, Annie Y. Liu, Enid C. Ibarra, Mark J. Miller

2020-Current year OA Pubs

Listeria monocytogenes (Lm) is a food-borne pathogen that causes severe bacterial gastroenteritis, with high rates of hospitalization and mortality. Lm is ubiquitous in soil, water and livestock, and can survive and proliferate at low temperatures. Following oral ingestion of contaminated food, Lm crosses the epithelium through intestinal goblet cells in a mechanism mediated by Lm InlA binding host E-cadherin. Importantly, human infections typically occur with Lm growing at or below room temperature, which is flagellated and motile. Even though many important human bacterial pathogens are flagellated, little is known regarding the effect of Lm motility on invasion and immune evasion. …