Digital Commons Network^™

Case Report: Long-Term Follow-Up Of Patients Who Received A Fimch Vaccine For Prevention Of Recurrent Urinary Tract Infections Caused By Antibiotic Resistant Enterobacteriaceae: A Case Report Series, Elise Perer, Helen Stacey, Terri Eichorn, Heidi Hughey, Julie Lawrence, Eric Cunningham, Mark O'Neil Johnson, Kevin Bacon, Andrew Kau, Scott J Hultgren, Thomas M Hooton, Jennifer L Harris

2020-Current year OA Pubs

Urinary tract infections (UTI) caused by carbapenem-resistant Enterobacteriaceae (CRE) are considered one of the most urgent health threats to humans according to the Centers for Disease Control (CDC), and the World Health Organization (WHO). A FimCH Vaccine expanded access study is being conducted in patients with a history of antibiotic resistant UTIs who are considered to be at risk for development of CRE UTI. This case series describes the clinical, safety and immunogenicity findings for four participants who received a FimCH four-vaccine series. Participants were followed for 12 months after administration of the fourth vaccine for safety, general health status …

Interventions Connecting Young People Living In Africa To Healthcare; A Systematic Review Using The Re-Aim Framework, Titilola Abike Gbaja-Biamila, Chisom Obiezu-Umeh, Ucheoma Nwaozuru, David Oladele, Alexis Engelhart, Thembekile Shato, Stacey Mason, Victoria Carter, Juliet Iwelunmor-Ezepue

2020-Current year OA Pubs

INTRODUCTION: Africa's young people are among the least focused groups in healthcare linkage. The disproportionally high burden of youth-related health problems is a burden, especially in developing regions like Africa, which have a high population of young people. More information is needed about factors that impact linkages in healthcare and the sustainability of health interventions among young people in Africa.

METHODS: A systematic literature search was performed from October 2020 to May 2022 in PubMed, CINAHL, Scopus, Global Health, and the Web of Science. Studies included in the review were conducted among young people aged 10-24 living in Africa, written …

Impahct: A Randomized Phase 2b/3 Study Of Inhaled Imatinib For Pulmonary Arterial Hypertension, Hunter Gillies, Murali M Chakinala, Benjamin T Dake, Jeremy P Feldman, Marius M Hoeper, Marc Humbert, Zhi-Cheng Jing, Jonathan Langley, Vallerie V Mclaughlin, Ralph W Niven, Stephan Rosenkranz, Xiaosha Zhang, Nicholas S Hill

2020-Current year OA Pubs

AV-101 (imatinib) powder for inhalation, an investigational dry powder inhaled formulation of imatinib designed to target the underlying pathobiology of pulmonary arterial hypertension, was generally well tolerated in healthy adults in a phase 1 single and multiple ascending dose study.

Factors Associated With Never Treatment And Acceptability Of Mass Drug Administration For The Elimination Of Lymphatic Filariasis In Guyana, 2021, Claudia Duguay, Reza A. Niles-Robin, Charles R. Thickstun, Horace Cox, Annastacia Sampson, Jean Seme-Fils Alexandre, Nathely Caleb-Mars, Charles W. Goss, Ana Morice, Ronaldo G. Carvalho Scholte, Alison Krentel

2020-Current year OA Pubs

Guyana remains one of four countries in the Americas endemic for lymphatic filariasis (LF). Elimination of LF requires repeated annual mass drug administration (MDA) with sufficient levels of coverage for success. This study assesses the acceptability and never treatment of LF MDA using data from a routine assessment survey in 2021. A subset of individuals, over 20 years of age (n = 2498), were selected to receive an expanded questionnaire to examine factors associated with acceptability and never treatment. Assessed factors include respondent demographics, knowledge, risk perceptions of LF, and opinions on the MDA programme. The majority (73%) of those …

Health System Barriers To Hypertension Care In Peru: Rapid Assessment To Inform Organizational-Level Change, Kendra N. Williams, Lindsay J. Underhill, Lisa De Las Fuentes, Elvin H. Geng, Victor G. Davila-Roman, Et Al.

2020-Current year OA Pubs

Traditional patient- and provider-level hypertension interventions have proven insufficient to halt hypertension as the leading cause of morbidity and mortality globally. Systems-level interventions are required to address factors challenging hypertension control across a social ecological framework, an under-studied topic particularly salient in low- and middle-income countries (LMICs) such as Peru. To inform such interventions, we sought to identify key health systems barriers to hypertension care in Puno, Peru. A participatory stakeholder workshop (October 2021) and 21 in-depth interviews (October 2021-March 2022) were conducted with 55 healthcare professionals (i.e., doctors, nurses, midwives, dentists, nutritionists), followed by a deductive qualitative analysis of …

Case Report: Deep Sequencing And Long-Read Genome Sequencing Refine Prior Genetic Analyses In Families With Apparent Gonadal Mosaicism In Pik3cd-Related Activated Pi3k Delta Syndrome, Halyn Orellana, Alex Paul, Nermina Saucier, Megan Cooper, Et Al.

2020-Current year OA Pubs

Gonadal and gonosomal mosaicism describe phenomena in which a seemingly healthy individual carries a genetic variant in a subset of their gonadal tissue or gonadal and somatic tissue(s), respectively, with risk of transmitting the variant to their offspring. In families with one or more affected offspring, occurrence of the same apparently

Recarving The Future: Bridging Car T-Cell Therapy Gaps With Synthetic Biology, Engineering, And Economic Insights, Alaa Ali, John F Dipersio

2020-Current year OA Pubs

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of hematologic malignancies, offering remarkable remission rates in otherwise refractory conditions. However, its expansion into broader oncological applications faces significant hurdles, including limited efficacy in solid tumors, safety concerns related to toxicity, and logistical challenges in manufacturing and scalability. This review critically examines the latest advancements aimed at overcoming these obstacles, highlighting innovations in CAR T-cell engineering, novel antigen targeting strategies, and improvements in delivery and persistence within the tumor microenvironment. We also discuss the development of allogeneic CAR T cells as off-the-shelf therapies, strategies to mitigate adverse effects, and …

Shared Decision-Making During Virtual Care Regarding Rheumatologic And Chronic Conditions: Qualitative Study Of Benefits, Pitfalls, And Optimization, Lisa Zickuhr, Catherine Mccarthy, Emma Nolan-Thomas, Tiffany Westrich-Robertson, Elizabeth A Baker, Janice L Hanson

2020-Current year OA Pubs

OBJECTIVE: Virtual care (VC) is an accepted modality of care delivery, and shared decision-making (SDM) benefits patients with rheumatologic and chronic conditions (RCCs). Unfortunately, research suggests reduced quality of SDM during VC. This study explores the benefits and shortcomings of SDM regarding RCCs during VC with suggestions for optimally using VC during SDM.

METHODS: Following Stiggelbout's framework for SDM, we conducted focus groups of patients with RCCs and providers to understand their experiences with SDM during VC, probing for facilitating and challenging factors. We conducted content analysis of the transcripts, defining themes, and inductively reasoned to identify relationships among themes. …

Everything But The Kitchen Sink: An Analysis Of Bacterial And Chemical Contaminants Found In Syringe Residue From People Who Inject Drugs, John A Wildenthal, Drew J Schwartz, Nathanial S Nolan, Lingxia Zhao, John I Robinson, Erin Jones, Raagini Jawa, Jeffrey P Henderson, Laura R Marks

2020-Current year OA Pubs

BACKGROUND: People who inject drugs (PWID) are at high risk of severe wounds, invasive infections, and overdoses. To date, there are few data on the bacterial and chemical contaminants PWID are exposed to when using illicitly manufactured fentanyls and stimulants.

METHODS: Previously used injection drug use equipment was recovered in St Louis, Missouri, by harm reduction organizations over a 12-month period. Syringe residue was analyzed for bacterial contaminants by routine culturing followed by whole genome sequencing of single bacterial isolates. Chemical adulterants in syringe residue were identified by liquid chromatography-mass spectrometry.

RESULTS: Bacteria were cultured from 58.75% of 160 syringes …

Researching Covid To Enhance Recovery (Recover) Pediatric Study Protocol: Rationale, Objectives And Design, Rachel S Gross, Deanna M. Barch, Andrew C. Heath, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.

OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of …

Stat1 Employs Myeloid Cell-Extrinsic Mechanisms To Regulate The Neutrophil Response And Provide Protection Against Invasive Klebsiella Pneumoniae Lung Infection, Shekina Gonzalez-Ferrer, Zeyu Xiong, Atish Gheware, Janet S Lee, Et Al.

2020-Current year OA Pubs

Klebsiella pneumoniae (KP) is an extracellular Gram-negative bacterium that causes infections in the lower respiratory and urinary tracts and the bloodstream. STAT1 is a master transcription factor that acts to maintain T cell quiescence under homeostatic conditions. Although STAT1 helps defend against systemic spread of acute KP intrapulmonary infection, whether STAT1 regulation of T cell homeostasis impacts pulmonary host defense during acute bacterial infection and injury is less clear. Using a clinical KP respiratory isolate and a pneumonia mouse model, we found that STAT1 deficiency led to an early neutrophil-dominant transcriptional profile and neutrophil recruitment in the lung preceding widespread …

Efficacy And Health-Related Quality Of Life Impact Of Fecal Microbiota, Live-Jslm: A Post Hoc Analysis Of Punch Cd3 Patients At First Recurrence Of Clostridioides Difficile Infection, Paul Feuerstadt, Jessica R Allegretti, Erik R Dubberke, Amy Guo, Adam Harvey, Min Yang, Viviana Garcia-Horton, Mirko Fillbrunn, Glenn Tillotson, Lindy L Bancke, Kerry Laplante, Kevin W Garey, Sahil Khanna

2020-Current year OA Pubs

INTRODUCTION: Clostridioides difficile infection (CDI) causes symptoms of varying severity and negatively impacts patients' health-related quality of life (HRQL). Despite antibiotic treatment, recurrence of CDI (rCDI) is common and imposes clinical and economic burdens on patients. Fecal microbiota, live-jslm (REBYOTA [RBL]) is newly approved in the USA for prevention of rCDI following antibiotic treatments. We analyzed efficacy and HRQL impact of RBL vs. placebo in patients at first rCDI using data from the phase 3 randomized, double-blind placebo-controlled clinical trial, PUNCH CD3.

METHODS: This post hoc analysis included patients at first rCDI fromPUNCH CD3. Treatment success (i.e., absence of diarrhea …

Cryptosporidium Infection Of Human Small Intestinal Epithelial Cells Induces Type Iii Interferon And Impairs Infectivity Of Rotavirus, Valentin Greigert, Iti Saraav, Juhee Son, Yinxing Zhu, Denise Dayao, Avan Antia, Saul Tzipori, William H Witola, Thaddeus S Stappenbeck, Siyuan Ding, L David Sibley

2020-Current year OA Pubs

Cryptosporidiosis is a major cause of severe diarrheal disease in infants from resource poor settings. The majority of infections are caused by the human-specific pathogen

Hyperbaric Oxygen Augments Susceptibility To C. Difficile Infection By Impairing Gut Microbiota Ability To Stimulate The Hif-1Α-Il-22 Axis In Ilc3, José L Fachi, Laís P Pral, Helder C Assis, Sarah Oliveira, Vinícius R Rodovalho, Jefferson A C Dos Santos, Mariane F Fernandes, Valquíria A Matheus, Renata Sesti-Costa, Paulo J Basso, Marina Flóro E Silva, Niels O S Câmara, Selma Giorgio, Marco Colonna, Marco A R Vinolo

2020-Current year OA Pubs

Hyperbaric oxygen (HBO) therapy is a well-established method for improving tissue oxygenation and is typically used for the treatment of various inflammatory conditions, including infectious diseases. However, its effect on the intestinal mucosa, a microenvironment known to be physiologically hypoxic, remains unclear. Here, we demonstrated that daily treatment with hyperbaric oxygen affects gut microbiome composition, worsening antibiotic-induced dysbiosis. Accordingly, HBO-treated mice were more susceptible to

Leishmania Major Surface Components And Dkk1 Signalling Via Lrp6 Promote Migration And Longevity Of Neutrophils In The Infection Site, Olivia C Ihedioha, Haley Q Marcarian, Anutr Sivakoses, Stephen M Beverley, Diane Mcmahon-Pratt, Alfred L M Bothwell

2020-Current year OA Pubs

BACKGROUND: Host-related factors highly regulate the increased circulation of neutrophils during

RESULTS: In this study, we further explored the potential role of DKK1-LRP6 signalling in the migration and longevity of activated neutrophils in the infection site using BALB/c mice with PMNs deficient in LRP6 (LRP6

CONCLUSION: Our results suggest that DKK1 signalling and

Unraveling The Role Of Hif And Epigenetic Regulation In Pulmonary Arterial Hypertension: Implications For Clinical Research And Its Therapeutic Approach, Ankita Mitra, Dan Yi, Zhiyu Dai, Vinicio De Jesus Perez

2020-Current year OA Pubs

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling with high pulmonary pressure, which ultimately leads to right heart failure and premature death. Emerging evidence suggests that both hypoxia and epigenetics play a pivotal role in the pathogenesis of PAH development. In this review article, we summarize the current developments in regulation of hypoxia inducible factor (HIF) isoforms in PAH vascular remodeling and the development of suitable animal models for discovery and testing of HIF pathway-targeting PAH therapeutics. In addition, we also discuss the epigenetic regulation of HIF-dependent isoforms in PAH and its therapeutic potential from a new perspective …

A Global Survey Of Self-Reported Cancer Screening Practices By Health Professionals For Kidney Transplant Candidates And Recipients, Nida Saleem, Naoka Murakami, Et Al.

2020-Current year OA Pubs

Cancer is a major cause of morbidity and mortality in kidney transplant recipients. Health professionals have a critical role in promoting cancer screening participation. From March 2023 to February 2024, an online survey was distributed to kidney transplant health professionals globally to assess their screening practices. We compared their reported screening practices to recommended guidelines and analyzed factors associated with these practices. We received 97 responses, and most were nephrologists (70%), and around 80% recommended breast, colorectal, and cervical cancer screening for kidney transplant candidates and recipients. About 85% recommended lung cancer screening for higher-risk individuals. Skin cancer screening recommendations …

Distinct Gene Expression Signatures Comparing Latent Tuberculosis Infection With Different Routes Of Bacillus Calmette-Guérin Vaccination, Richard F Silver, Mei Xia, Chad E Storer, Jessica R Jarvela, Michelle C Moyer, Azra Blazevic, David A Stoeckel, Erin K Rakey, Jan M Tennant, Johannes B Goll, Richard D Head, Daniel F Hoft

2020-Current year OA Pubs

Tuberculosis remains an international health threat partly because of limited protection from pulmonary tuberculosis provided by standard intradermal vaccination with Bacillus of Calmette and Guérin (BCG); this may reflect the inability of intradermal vaccination to optimally induce pulmonary immunity. In contrast, respiratory Mycobacterium tuberculosis infection usually results in the immune-mediated bacillary containment of latent tuberculosis infection (LTBI). Here we present RNA-Seq-based assessments of systemic and pulmonary immune cells from LTBI participants and recipients of intradermal and oral BCG. LTBI individuals uniquely display ongoing immune activation and robust CD4 T cell recall responses in blood and lung. Intradermal BCG is associated …

Vodka2: A Fast And Accurate Method To Detect Non-Standard Viral Genomes From Large Rna-Seq Data Sets, Emna Achouri, Sébastien A Felt, Matthew Hackbart, Nicole S Rivera-Espinal, Carolina B López

2020-Current year OA Pubs

During viral replication, viruses carrying an RNA genome produce non-standard viral genomes (nsVGs), including copy-back viral genomes (cbVGs) and deletion viral genomes (delVGs), that play a crucial role in regulating viral replication and pathogenesis. Because of their critical roles in determining the outcome of RNA virus infections, the study of nsVGs has flourished in recent years, exposing a need for bioinformatic tools that can accurately identify them within next-generation sequencing data obtained from infected samples. Here, we present our data analysis pipeline, Viral Opensource DVG Key Algorithm 2 (VODKA2), that is optimized to run on a parallel computing environment for …

What Do Infectious Disease Specialists Think About Managing Long Covid?, Maureen D Lyons, Susan E Beekmann, Philip M Polgreen, Jonas Marschall

2020-Current year OA Pubs

This survey of infectious disease providers on long COVID care revealed a lack of familiarity with existing resources, a sentiment of missing guidelines, and scarcity of dedicated care centers. The low response rate suggests that infectious disease specialists do not consider themselves as the primary providers of long COVID care.

Deep Learning-Based Phenotyping Reclassifies Combined Hepatocellular-Cholangiocarcinoma, Julien Calderaro, Pooja Navale, Et Al.

2020-Current year OA Pubs

Primary liver cancer arises either from hepatocytic or biliary lineage cells, giving rise to hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICCA). Combined hepatocellular- cholangiocarcinomas (cHCC-CCA) exhibit equivocal or mixed features of both, causing diagnostic uncertainty and difficulty in determining proper management. Here, we perform a comprehensive deep learning-based phenotyping of multiple cohorts of patients. We show that deep learning can reproduce the diagnosis of HCC vs. CCA with a high performance. We analyze a series of 405 cHCC-CCA patients and demonstrate that the model can reclassify the tumors as HCC or ICCA, and that the predictions are consistent with clinical …

Older Adults' And Caregivers' Perceptions About Urinary Tract Infection And Asymptomatic Bacteriuria Guidelines: A Qualitative Exploration, Michael J Durkin, Viktoria Schmitz, Kevin Hsueh, Zoe Troubh, Mary C Politi

2020-Current year OA Pubs

OBJECTIVE: To explore older adults' and caregivers' knowledge and perceptions of guidelines for appropriate antibiotics use for bacteria in the urine.

DESIGN: Semi-structured qualitative interviews.

SETTING: Infectious disease clinics, community senior living facilities, memory care clinics, and general public.

PARTICIPANTS: Patients 65 years or older diagnosed with a urinary tract infection (UTI) in the past two years, or caregivers of such patients.

METHODS: We conducted interviews between March and July 2023. We developed an interview guide based on the COM-B (capability, opportunity, motivation-behavior) behavior change framework. We thematically analyzed written transcripts of audio-recorded interviews using inductive and deductive coding techniques. …

Core Warming Of Coronavirus Disease 2019 Patients Undergoing Mechanical Ventilation: A Pilot Study, Nathaniel P Bonfanti, Nicholas M Mohr, David C Willms, Roger J Bedimo, Emily Gundert, Kristina L Goff, Erik B Kulstad, Anne M Drewry

2020-Current year OA Pubs

Fever is a recognized protective factor in patients with sepsis, and growing data suggest beneficial effects on outcomes in sepsis with elevated temperature, with a recent pilot randomized controlled trial (RCT) showing lower mortality by warming afebrile sepsis patients in the intensive care unit (ICU). The objective of this prospective single-site RCT was to determine if core warming improves respiratory physiology of mechanically ventilated patients with coronavirus disease 2019 (COVID-19), allowing earlier weaning from ventilation, and greater overall survival. A total of 19 patients with mean age of 60.5 (±12.5) years, 37% female, mean weight 95.1 (±18.6) kg, and mean …

What Can The Plasma Proteome Tell Us About Platelets And (Vice Versa)?, Steven Bruzek, Marisol Betensky, Jorge Di Paola, Thomas Diacovo, Neil Goldenberg, Vera Ignjatovic

2020-Current year OA Pubs

Multi-omics approaches are being used increasingly to study physiological and pathophysiologic processes. Proteomics specifically focuses on the study of proteins as functional elements and key contributors to, and markers of the phenotype, as well as targets for diagnostic and therapeutic approaches. Depending on the condition, the plasma proteome can mirror the platelet proteome, and hence play an important role in elucidating both physiologic and pathologic processes. In fact, both plasma and platelet protein signatures have been shown to be important in the setting of thrombosis-prone disease states such as atherosclerosis and cancer. Plasma and platelet proteomes are increasingly being studied …

Correlating Deep Learning-Based Automated Reference Kidney Histomorphometry With Patient Demographics And Creatinine, Nicholas Lucarelli, Brandon Ginley, Jarcy Zee, Sayat Mimar, Anindya S. Paul, Sanjay Jain, Seung Seok Han, Luis Rodrigues, Tezcan Ozrazgat-Baslanti, Michelle L. Wong, Girish Nadkarni, William L. Clapp, Kuang-Yu Jen, Pinaki Sarder

2020-Current year OA Pubs

KEY POINTS: The authors leverage the unique benefits of panoptic segmentation to perform the largest ever quantitation of reference kidney morphometry. Kidney features vary with age and sex; and glomeruli size may intricately link to creatinine, defying prior notions.

BACKGROUND: Reference histomorphometric data of healthy human kidneys are largely lacking because of laborious quantitation requirements. Correlating histomorphometric features with clinical parameters through machine learning approaches can provide valuable information about natural population variance. To this end, we leveraged deep learning (DL), computational image analysis, and feature analysis to associate the relationship of histomorphometry with patient age, sex, serum creatinine (SCr), …

Optimized Strategy For Real-Time Qpcr Detection Of Onchocerca Volvulus Dna In Pooled Simulium Sp. Blackfly Vectors, Mary Doherty, Peter U. Fischer, Et Al.

2020-Current year OA Pubs

BACKGROUND: Onchocerca volvulus is a filarial parasite that is a major cause of dermatitis and blindness in endemic regions primarily in sub-Saharan Africa. Widespread efforts to control the disease caused by O. volvulus infection (onchocerciasis) began in 1974 and in recent years, following successful elimination of transmission in much of the Americas, the focus of efforts in Africa has moved from control to the more challenging goal of elimination of transmission in all endemic countries. Mass drug administration (MDA) with ivermectin has reached more than 150 million people and elimination of transmission has been confirmed in four South American countries, …

Endothelial Adam10 Utilization Defines A Molecular Pathway Of Vascular Injury In Mice With Bacterial Sepsis, Danielle N. Alfano, Mark J. Miller, Juliane Bubeck-Wardenburg

2020-Current year OA Pubs

The endothelium plays a critical role in the host response to infection and has been a focus of investigation in sepsis. While it is appreciated that intravascular thrombus formation, severe inflammation, and loss of endothelial integrity impair tissue oxygenation during sepsis, the precise molecular mechanisms that lead to endothelial injury remain poorly understood. We demonstrate here that endothelial ADAM10 was essential for the pathogenesis of Staphylococcus aureus sepsis, contributing to α-toxin-mediated (Hla-mediated) microvascular thrombus formation and lethality. As ADAM10 is essential for endothelial development and homeostasis, we examined whether other major human sepsis pathogens also rely on ADAM10-dependent pathways in …

Gut Microbiota Induces Weight Gain And Inflammation In The Gut And Adipose Tissue Independent Of Manipulations In Diet, Genetics, And Immune Development, Devesha H Kulkarni, Brigida Rusconi, Alexandria N Floyd, Elisabeth L Joyce, Khushi B Talati, Hrishi Kousik, Dereck Alleyne, Dalia L Harris, Lorena Garnica, Ryan Mcdonough, Shay S Bidani, Hrishikesh S Kulkarni, Elizabeth P Newberry, Keely G Mcdonald, Rodney D Newberry

2020-Current year OA Pubs

Obesity and the metabolic syndrome are complex disorders resulting from multiple factors including genetics, diet, activity, inflammation, and gut microbes. Animal studies have identified roles for each of these, however the contribution(s) specifically attributed to the gut microbiota remain unclear, as studies have used combinations of genetically altered mice, high fat diet, and/or colonization of germ-free mice, which have an underdeveloped immune system. We investigated the role(s) of the gut microbiota driving obesity and inflammation independent of manipulations in diet and genetics in mice with fully developed immune systems. We demonstrate that the human obese gut microbiota alone was sufficient …

Stratification Of Risk For Emergent Intracranial Abnormalities In Children With Headaches: A Pediatric Emergency Care Applied Research Network (Pecarn) Study Protocol, Daniel S Tsze, Kimberly S Quayle, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Headache is a common chief complaint of children presenting to emergency departments (EDs). Approximately 0.5%-1% will have emergent intracranial abnormalities (EIAs) such as brain tumours or strokes. However, more than one-third undergo emergent neuroimaging in the ED, resulting in a large number of children unnecessarily exposed to radiation. The overuse of neuroimaging in children with headaches in the ED is driven by clinician concern for life-threatening EIAs and lack of clarity regarding which clinical characteristics accurately identify children with EIAs. The study objective is to derive and internally validate a stratification model that accurately identifies the risk of EIA …

Heterogeneous Cardiac Sympathetic Innervation Gradients Promote Arrhythmogenesis In Murine Dilated Cardiomyopathy, Al-Hassan J Dajani, Carla Valenzuela-Ripoll, Ali Javaheri, Et Al.

2020-Current year OA Pubs

Ventricular arrhythmias (VAs) in heart failure are enhanced by sympathoexcitation. However, radiotracer studies of catecholamine uptake in failing human hearts demonstrate a proclivity for VAs in patients with reduced cardiac sympathetic innervation. We hypothesized that this counterintuitive finding is explained by heterogeneous loss of sympathetic nerves in the failing heart. In a murine model of dilated cardiomyopathy (DCM), delayed PET imaging of sympathetic nerve density using the catecholamine analog [11C]meta-Hydroxyephedrine demonstrated global hypoinnervation in ventricular myocardium. Although reduced, sympathetic innervation in 2 distinct DCM models invariably exhibited transmural (epicardial to endocardial) gradients, with the endocardium being devoid of sympathetic nerve …