Digital Commons Network^™

Lifespan Benefits For The Combination Of Rapamycin Plus Acarbose And For Captopril In Genetically Heterogeneous Mice, Randy Strong, Kerry Kornfeld, Et Al.

2020-Current year OA Pubs

Mice bred in 2017 and entered into the C2017 cohort were tested for possible lifespan benefits of (R/S)-1,3-butanediol (BD), captopril (Capt), leucine (Leu), the Nrf2-activating botanical mixture PB125, sulindac, syringaresinol, or the combination of rapamycin and acarbose started at 9 or 16 months of age (RaAc9, RaAc16). In male mice, the combination of Rapa and Aca started at 9 months and led to a longer lifespan than in either of the two prior cohorts of mice treated with Rapa only, suggesting that this drug combination was more potent than either of its components used alone. In females, lifespan in mice …

Primary Open-Angle Glaucoma Diagnosis From Optic Disc Photographs Using A Siamese Network, Mingquan Lin, Lei Liu, Mae Gordon, Michael Kass, Fei Wang, Sarah H Van Tassel, Yifan Peng

2020-Current year OA Pubs

PURPOSE: Primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness in the United States and worldwide. Although deep learning methods have been proposed to diagnose POAG, these methods all used a single image as input. Contrastingly, glaucoma specialists typically compare the follow-up image with the baseline image to diagnose incident glaucoma. To simulate this process, we proposed a Siamese neural network, POAGNet, to detect POAG from optic disc photographs.

DESIGN: The POAGNet, an algorithm for glaucoma diagnosis, is developed using optic disc photographs.

PARTICIPANTS: The POAGNet was trained and evaluated on 2 data sets: (1) 37 …

Examining Shortened Versions Of The Social Responsiveness Scale For Use In Autism Spectrum Disorder Prediction And As A Quantitative Trait Measure: Results From A Validation Study Of 3-5 Year Old Children, Kristen Lyall, Juliette Rando, Bridget Toroni, Tobechukwu Ezeh, John N Constantino, Lisa A Croen, Brigid Garvin, Kate Piselli, James Connell, Aaron J Kaat, Craig J Newschaffer, Program Collaborators For Environmental Influences On Child Health Outcomes

2020-Current year OA Pubs

BACKGROUND: The Social Responsiveness Scale (SRS) is a 65-item measure yielding a continuous score capturing autism-related traits. Scores based on SRS item subsets have been analytically examined but administration of shortened versions has not been evaluated prospectively.

OBJECTIVE: The goal of this study was to compare psychometric properties of two shortened versions of the SRS to the full 65-item SRS, in young children from both a clinical and general population setting.

METHODS: Study participants (aged 3-5 years) were drawn from the AJ Drexel Autism Institute clinic (

RESULTS: Overall, distributional properties of the three administration methods were highly comparable, with …

Approaches To Healthcare Personnel Exemption Requests From Coronavirus Disease 2019 (Covid-19) Vaccination: Results Of A National Survey, Thomas R Talbot, Susan E Beekmann, Hilary M Babcock, Philip M Polgreen

2020-Current year OA Pubs

OBJECTIVE: Although a growing number of healthcare facilities are implementing healthcare personnel (HCP) coronavirus disease 2019 (COVID-19) vaccination requirements, vaccine exemption request management as a part of such programs is not well described.

DESIGN: Cross-sectional survey.

PARTICIPANTS: Infectious disease (ID) physician members of the Emerging Infections Network with infection prevention or hospital epidemiology responsibilities.

METHODS: Eligible persons were sent a web-based survey focused on hospital plans and practices around exemption allowances from HCP COVID-19 vaccine requirements.

RESULTS: Of the 695 ID physicians surveyed, 263 (38%) responded. Overall, 160 respondent institutions (92%) allowed medical exemptions, whereas 132 (76%) allowed religious exemptions. …

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

Hiv Care Experiences And Health Priorities During The First Wave Of Covid-19: Clients' Perspectives - A Qualitative Study In Lusaka, Zambia, Njekwa Mukamba, Anjali Sharma, Chanda Mwamba, Herbert Nyirenda, Marksman Foloko, Kasapo Lumbo, Katerina Christopoulos, Sandra Simbeza, Kombatende Sikombe, Charles B Holmes, Elvin H Geng, Izukanji Sikazwe, Carolyn Bolton-Moore, Laura K Beres

2020-Current year OA Pubs

BACKGROUND: The novel COVID-19 pandemic threatened to disrupt access to human immunodeficiency (HIV) treatment for persons living with HIV (PLHIV), two-thirds of whom live in sub-Saharan Africa. To inform a health system response supportive of continuity of care, we sought to understand clients' HIV care experiences and health priorities during the first wave of COVID-19 outbreak in Lusaka, Zambia.

METHODS: Leveraging a study cohort of those who completed periodic SMS surveys on HIV care, we purposefully sampled 25 PLHIV after first confirmed COVID-19 case was reported in Zambia on 18

RESULTS: All participants were aware of COVID-19, and HIV care …

Immune Checkpoint Inhibitor Therapy And Outcomes From Sars-Cov-2 Infection In Patients With Cancer: A Joint Analysis Of Oncovid And Esmo-Cocare Registries, Alessio Cortellini, Gino M Dettorre, Et Al.

2020-Current year OA Pubs

BACKGROUND: As management and prevention strategies against COVID-19 evolve, it is still uncertain whether prior exposure to immune checkpoint inhibitors (ICIs) affects COVID-19 severity in patients with cancer.

METHODS: In a joint analysis of ICI recipients from OnCovid (NCT04393974) and European Society for Medical Oncology (ESMO) CoCARE registries, we assessed severity and mortality from SARS-CoV-2 in vaccinated and unvaccinated patients with cancer and explored whether prior immune-related adverse events (irAEs) influenced outcome from COVID-19.

FINDINGS: The study population consisted of 240 patients diagnosed with COVID-19 between January 2020 and February 2022 exposed to ICI within 3 months prior to COVID-19 …

Single-Cell Rna Sequencing Identifies A Paracrine Interaction That May Drive Oncogenic Notch Signaling In Human Adenoid Cystic Carcinoma, Anuraag S. Parikh, Avishai Wizel, Daniel Davis, Armida Lefranc-Torres, Alejandro I. Rodarte-Rascon, Lauren E. Miller, Kevin S. Emerick, Mark A. Varvares, Daniel G. Deschler, William C. Faquin, Jon C. Aster, Derrick T. Lin, Bradley E. Bernstein, Yotam Drier, Sidharth V. Puram

2020-Current year OA Pubs

Salivary adenoid cystic carcinoma (ACC) is a rare, biologically unique biphasic tumor that consists of malignant myoepithelial and luminal cells. MYB and Notch signaling have been implicated in ACC pathophysiology, but in vivo descriptions of these two programs in human tumors and investigation into their active coordination remain incomplete. We utilize single-cell RNA sequencing to profile human head and neck ACC, including a comparison of primary ACC with a matched local recurrence. We define expression heterogeneity in these rare tumors, uncovering diversity in myoepithelial and luminal cell expression. We find differential expression of Notch ligands DLL1, JAG1, and JAG2 in …

Gantenerumab: An Anti-Amyloid Monoclonal Antibody With Potential Disease-Modifying Effects In Early Alzheimer's Disease, Randall J Bateman, Jeffrey Cummings, Scott Schobel, Stephen Salloway, Bruno Vellas, Mercè Boada, Sandra E Black, Kaj Blennow, Paulo Fontoura, Gregory Klein, Sheila Seleri Assunção, Janice Smith, Rachelle S Doody

2020-Current year OA Pubs

BACKGROUND: This review describes the research and development process of gantenerumab, a fully human anti-amyloid monoclonal antibody in development to treat early symptomatic and asymptomatic Alzheimer's disease (AD). Anti-amyloid monoclonal antibodies can substantially reverse amyloid plaque pathology and may modify the course of the disease by slowing or stopping its clinical progression. Several molecules targeting amyloid have failed in clinical development due to drug-related factors (e.g., treatment-limiting adverse events, low potency, poor brain penetration), study design/methodological issues (e.g., disease stage, lack of AD pathology confirmation), and other factors. The US Food and Drug Administration's approval of aducanumab, an anti-amyloid monoclonal …

Fgfr2b Signalling Restricts Lineage-Flexible Alveolar Progenitors During Mouse Lung Development And Converges In Mature Alveolar Type 2 Cells, Matthew R Jones, Arun Lingampally, Negah Ahmadvand, Lei Chong, Jin Wu, Jochen Wilhem, Ana Ivonne Vazquez-Armendariz, Meshal Ansari, Susanne Herold, David M Ornitz, Herbert B Schiller, Cho-Ming Chao, Jin-San Zhang, Gianni Carraro, Saverio Bellusci

2020-Current year OA Pubs

The specification, characterization, and fate of alveolar type 1 and type 2 (AT1 and AT2) progenitors during embryonic lung development are poorly defined. Current models of distal epithelial lineage formation fail to capture the heterogeneity and dynamic contribution of progenitor pools present during early development. Furthermore, few studies explore the pathways involved in alveolar progenitor specification and fate. In this paper, we build upon our previously published work on the regulation of airway epithelial progenitors by fibroblast growth factor receptor 2b (FGFR2b) signalling during early (E12.5) and mid (E14.5) pseudoglandular stage lung development. Our results suggest that a significant proportion …

Clinical Management Of Supratentorial Non-Skull Case Meningiomas, Adefisayo Adekanmbi, Mark W Youngblood, Constantine L Karras, Ephraim A Oyetunji, John Kalapurakal, Craig M Horbinski, Hinda Najem, Virginia B Hill, James P Chandler, Amy B Heimberger, Stephen T Magill, Rimas V Lukas

2020-Current year OA Pubs

Supratentorial non-skull base meningiomas are the most common primary central nervous system tumor subtype. An understanding of their pathophysiology, imaging characteristics, and clinical management options will prove of substantial value to the multi-disciplinary team which may be involved in their care. Extensive review of the broad literature on the topic is conducted. Narrowing the scope to meningiomas located in the supratentorial non-skull base anatomic location highlights nuances specific to this tumor subtype. Advances in our understanding of the natural history of the disease and how findings from both molecular pathology and neuroimaging have impacted our understanding are discussed. Clinical management …

Comprehensive Transcriptomic Analysis Of Vista In Acute Myeloid Leukemia: Insights Into Its Prognostic Value, Simona Pagliuca, Carmelo Gurnari, Keman Zhang, Tariq Kewan, Waled Bahaj, Minako Mori, Ishani Nautiyal, Marie Thérèse Rubio, Francesca Ferraro, Jaroslaw P Maciejewski, Li Wang, Valeria Visconte

2020-Current year OA Pubs

The V-domain Ig suppressor of T-cell activation (VISTA) has been recognized as a critical negative regulator of antitumor immune response and is gaining growing interest as a potential pharmacological target in immunotherapy. This molecule is highly expressed in hematopoietic stem cells and myeloid compartment, and it has been found upmodulated in acute myeloid leukemia (AML). However, VISTA-associated immune features are relatively unexplored in myeloid malignancies. Herein, we aimed to explore whether this immune checkpoint regulator could play a role in the generation of an immune escape environment in AML patients. We characterized VISTA mRNA expression levels in leukemia cell lines …

Non-Standard Viral Genome-Derived Rna Activates Tlr3 And Type I Ifn Signaling To Induce Cdc1-Dependent Cd8+ T-Cell Responses During Vaccination In Mice, Devin G Fisher, Victoria Gnazzo, David J Holthausen, Carolina B López

2020-Current year OA Pubs

There is a critical need to develop vaccine adjuvants that induce robust immune responses able to protect against intracellular pathogens, including viruses. Previously, we described defective viral genome-derived oligonucleotides (DDOs) as novel adjuvants that strongly induce type 1 immune responses, including protective Th1 CD4+ T-cells and effector CD8+ T-cells in mice. Here, we unravel the early innate response required for this type 1 immunity induction. Upon DDO subcutaneous injection, type 1 conventional dendritic cells (cDC1s) accumulate rapidly in the draining lymph node in a Toll-like receptor 3 (TLR3)- and type I interferon (IFN)-dependent manner. cDC1 accumulation in the lymph node …

Determining Epigenetic Memory In Kidney Proximal Tubule Cell Derived Induced Pluripotent Stem Cells Using A Quadruple Transgenic Reprogrammable Mouse, Gabriel Khelifi, Theresa Chow, Jennifer Whiteley, Victoire Fort, Benjamin D Humphreys, Samer M I Hussein, Ian M Rogers

2020-Current year OA Pubs

The majority of nucleated somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs). The process of reprogramming involves epigenetic remodelling to turn on pluripotency-associated genes and turn off lineage-specific genes. Some evidence shows that iPSCs retain epigenetic marks of their cell of origin and this "epigenetic memory" influences their differentiation potential, with a preference towards their cell of origin. Here, we reprogrammed proximal tubule cells (PTC) and tail tip fibroblasts (TTF), from a reprogrammable mouse to iPSCs and differentiated the iPSCs to renal progenitors to understand if epigenetic memory plays a role in renal differentiation. This model allowed …

Immune Phenotypes That Are Associated With Subsequent Covid-19 Severity Inferred From Post-Recovery Samples, Thomas Liechti, Yaser Iftikhar, Massimo Mangino, Margaret Beddall, Charles W Goss, Jane A O'Halloran, Philip A Mudd, Mario Roederer

2020-Current year OA Pubs

Severe COVID-19 causes profound immune perturbations, but pre-infection immune signatures contributing to severe COVID-19 remain unknown. Genome-wide association studies (GWAS) identified strong associations between severe disease and several chemokine receptors and molecules from the type I interferon pathway. Here, we define immune signatures associated with severe COVID-19 using high-dimensional flow cytometry. We measure the cells of the peripheral immune system from individuals who recovered from mild, moderate, severe or critical COVID-19 and focused only on those immune signatures returning to steady-state. Individuals that suffered from severe COVID-19 show reduced frequencies of T cell, mucosal-associated invariant T cell (MAIT) and dendritic …

Premature Ovarian Insufficiency In Clpb Deficiency: Transcriptomic, Proteomic And Phenotypic Insights, Elena J Tucker, Julia T Warren, Et Al.

2020-Current year OA Pubs

CONTEXT: Premature ovarian insufficiency (POI) is a common form of female infertility that usually presents as an isolated condition but can be part of various genetic syndromes. Early diagnosis and treatment of POI can minimize comorbidity and improve health outcomes.

OBJECTIVE: We aimed to determine the genetic cause of syndromic POI, intellectual disability, neutropenia, and cataracts.

METHODS: We performed whole-exome sequencing (WES) followed by functional validation via RT-PCR, RNAseq, and quantitative proteomics, as well as clinical update of previously reported patients with variants in the caseinolytic peptidase B (CLPB) gene.

RESULTS: We identified causative variants in CLPB, encoding a mitochondrial …

Csf Tau Microtubule-Binding Region Identifies Pathological Changes In Primary Tauopathies, Kanta Horie, Nicolas R Barthélemy, Yingxin He, Albert A Davis, Celeste M Karch, Richard J Perrin, Rama K Koppisetti, Faris Shaikh, Nupur Ghoshal, Randall J Bateman, Chihiro Sato, Et Al.

2020-Current year OA Pubs

Despite recent advances in fluid biomarker research in Alzheimer's disease (AD), there are no fluid biomarkers or imaging tracers with utility for diagnosis and/or theragnosis available for other tauopathies. Using immunoprecipitation and mass spectrometry, we show that 4 repeat (4R) isoform-specific tau species from microtubule-binding region (MTBR-tau

Wakeful Rest Benefits Recall, But Not Recognition, Of Incidentally Encoded Memory Stimuli In Younger And Older Adults, Peter R Millar, David A Balota

2020-Current year OA Pubs

Older adults exhibit deficits in episodic memory tasks, which have often been attributed to encoding or retrieval deficits, with little attention to consolidation mechanisms. More recently, researchers have attempted to measure consolidation in the context of a behavioral experiment using the wakeful rest paradigm (i.e., a brief, quiet period of minimal stimulation, which facilitates memory performance, compared to a distractor task). Critically, older adults might not produce this effect, given established age differences in other episodic memory processes and mind-wandering. In three experiments, we directly compared younger and older adults in modified versions of the wakeful rest paradigm. Critically, we …

Stakeholder Engagement In Eight Comparative Effectiveness Trials In African Americans And Latinos With Asthma, Tiffany Dy, Winifred J Hamilton, C Bradley Kramer, Andrea Apter, Jerry A Krishnan, James W Stout, Stephen J Teach, Alex Federman, John Elder, Tyra Bryant-Stephens, Rebecca J Bruhl, Shawni Jackson, Kaharu Sumino

2020-Current year OA Pubs

BACKGROUND: The effects of stakeholder engagement, particularly in comparative effectiveness trials, have not been widely reported. In 2014, eight comparative effectiveness studies targeting African Americans and Hispanics/Latinos with uncontrolled asthma were funded by the Patient-Centered Outcomes Research Institute (PCORI) as part of its Addressing Disparities Program. Awardees were required to meaningfully involve patients and other stakeholders. Using specific examples, we describe how these stakeholders substantially changed the research protocols and in other ways participated meaningfully as full partners in the development and conduct of the eight studies.

METHODS: Using the method content analysis of cases, we identified themes regarding the …

Mahpic Malaria Systems Biology Data From Plasmodium Cynomolgi Sporozoite Longitudinal Infections In Macaques, Jeremy D Debarry, Xuntian Jiang, Daniel S Ory, Et Al.

2020-Current year OA Pubs

Plasmodium cynomolgi causes zoonotic malarial infections in Southeast Asia and this parasite species is important as a model for Plasmodium vivax and Plasmodium ovale. Each of these species produces hypnozoites in the liver, which can cause relapsing infections in the blood. Here we present methods and data generated from iterative longitudinal systems biology infection experiments designed and performed by the Malaria Host-Pathogen Interaction Center (MaHPIC) to delve deeper into the biology, pathogenesis, and immune responses of P. cynomolgi in the Macaca mulatta host. Infections were initiated by sporozoite inoculation. Blood and bone marrow samples were collected at defined timepoints for …

Muscle-Specific Ablation Of Glucose Transporter 1 (Glut1) Does Not Impair Basal Or Overload-Stimulated Skeletal Muscle Glucose Uptake, Shawna L Mcmillin, Parker L Evans, William M Taylor, Luke A Weyrauch, Tyler J Sermersheim, Steven S Welc, Monique R Heitmeier, Richard C Hresko, Paul W Hruz, Francoise Koumanov, Geoffrey D Holman, E Dale Abel, Carol A Witczak

2020-Current year OA Pubs

Glucose transporter 1 (GLUT1) is believed to solely mediate basal (insulin-independent) glucose uptake in skeletal muscle; yet recent work has demonstrated that mechanical overload, a model of resistance exercise training, increases muscle GLUT1 levels. The primary objective of this study was to determine if GLUT1 is necessary for basal or overload-stimulated muscle glucose uptake. Muscle-specific GLUT1 knockout (mGLUT1KO) mice were generated and examined for changes in body weight, body composition, metabolism, systemic glucose regulation, muscle glucose transporters, and muscle [

Multilevel Correlates Of Domain-Specific Physical Activity Among Rural Adults - A Cross-Sectional Study, Alan M Beck, Natalicio H Serrano, Audrey Toler, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: Increasing physical activity (PA) in rural communities is a vital prevention tactic in multiple chronic diseases; however, little is known on the multilevel correlates of PA rural areas. A better understanding of domain-specific PA adds context for promoting PA in rural communities. The current study sought to determine factors associated with domain-specific and overall moderate-vigorous physical activity (MVPA) in rural communities.

METHODS: Surveys were conducted across 14 rural mid-Western communities, with the final analytical sample including 1241 adults (ages 19-96, M = 57.0 [SD = 16.7], 67.8% female, 83.8% white). Generalized linear models with negative binomial distributions examined the …

Cortex-Wide Response Mode Of Vip-Expressing Inhibitory Neurons By Reward And Punishment, Zoltán Szadai, Hyun-Jae Pi, Quentin Chevy, Katalin Ócsai, Dinu F Albeanu, Balázs Chiovini, Gergely Szalay, Gergely Katona, Adam Kepecs, Balázs Rózsa

2020-Current year OA Pubs

Neocortex is classically divided into distinct areas, each specializing in different function, but all could benefit from reinforcement feedback to inform and update local processing. Yet it remains elusive how global signals like reward and punishment are represented in local cortical computations. Previously, we identified a cortical neuron type, vasoactive intestinal polypeptide (VIP)-expressing interneurons, in auditory cortex that is recruited by behavioral reinforcers and mediates disinhibitory control by inhibiting other inhibitory neurons. As the same disinhibitory cortical circuit is present virtually throughout cortex, we wondered whether VIP neurons are likewise recruited by reinforcers throughout cortex. We monitored VIP neural activity …

Dose-Dependent Von Willebrand Factor Inhibition By Aptamer Bb-031 Correlates With Thrombolysis In A Microfluidic Model Of Arterial Occlusion, Susan M Shea, Kimberly A Thomas, Rassam M G Rassam, Emily P Mihalko, Christina Daniel, Bruce A Sullenger, Philip C Spinella, Shahid M Nimjee

2020-Current year OA Pubs

Von Willebrand Factor (VWF) plays a critical role in thrombus formation, stabilization, and propagation. Previous studies have demonstrated that targeted inhibition of VWF induces thrombolysis when administered in vivo in animal models of ischemic stroke. The study objective was to quantify dose-dependent inhibition of VWF-platelet function and its relationship with thrombolysis using BB-031, an aptamer that binds VWF and inhibits its function. VWF:Ac, VWF:RCo, T-TAS, and ristocetin-induced impedance aggregometry were used to assess BB-031-mediated inhibition of VWF. Reductions in original thrombus surface area and new deposition during administration of treatment were measured in a microfluidic model of arterial thrombolysis. Rotational …

Myostatin Is A Negative Regulator Of Adult Neurogenesis After Spinal Cord Injury In Zebrafish, Vishnu Muraleedharan Saraswathy, Lili Zhou, Anthony R Mcadow, Brooke Burris, Deepika Dogra, Sven Reischauer, Mayssa H Mokalled

2020-Current year OA Pubs

Intrinsic and extrinsic inhibition of neuronal regeneration obstruct spinal cord (SC) repair in mammals. In contrast, adult zebrafish achieve functional recovery after complete SC transection. While studies of innate SC regeneration have focused on axon regrowth as a primary repair mechanism, how local adult neurogenesis affects functional recovery is unknown. Here, we uncover dynamic expression of zebrafish myostatin b (mstnb) in a niche of dorsal SC progenitors after injury. mstnb mutants show impaired functional recovery, normal glial and axonal bridging across the lesion, and an increase in the profiles of newborn neurons. Molecularly, neuron differentiation genes are upregulated, while the …

Chatbot-Delivered Cognitive Behavioral Therapy In Adolescents With Depression And Anxiety During The Covid-19 Pandemic: Feasibility And Acceptability Study, Ginger Nicol, Ruoyun Wang, Sharon Graham, Sherry Dodd, Jane Garbutt

2020-Current year OA Pubs

BACKGROUND: Symptoms of depression and anxiety, suicidal ideation, and self-harm have escalated among adolescents to crisis levels during the COVID-19 pandemic. As a result, primary care providers (PCPs) are often called on to provide first-line care for these youth. Digital health interventions can extend mental health specialty care, but few are evidence based. We evaluated the feasibility of delivering an evidence-based mobile health (mHealth) app with an embedded conversational agent to deliver cognitive behavioral therapy (CBT) to symptomatic adolescents presenting in primary care settings during the pandemic.

OBJECTIVE: In this 12-week pilot study, we evaluated the feasibility of delivering the …

Transversus Abdominis Plane Block With Different Bupivacaine Concentrations In Children Undergoing Unilateral Inguinal Hernia Repair: A Single-Blind Randomized Clinical Trial, Meltem Savran Karadeniz, Ayşe Gülşah Atasever, Emine Aysu Salviz, Emre Sertaç Bingül, Hayriye Şentürk Çiftçi, Müşerref Beril Dinçer, Mukadder Orhan Sungur

2020-Current year OA Pubs

BACKGROUND: Current knowledge on the ideal local anesthetic concentration for the ultrasound-guided transversus abdominis plane block (TAPB) in pediatrics is scarce. The purpose of this study is to compare the efficacy of US-guided TAPB at two different concentrations of bupivacaine in pediatrics undergoing unilateral inguinal hernia repair.

METHODS: After random allocation, 74 children aged 1-8 were randomized to receive US-guided TAPB by using 1 mg.kg

RESULTS: Sixty-four children were recruited for the study. Postoperative pain scores were equal between the two groups. There was no need for a rescue analgesic in any group after the postoperative 6

CONCLUSION: TAPB using …

Let's Talk About Antibiotics: A Randomised Trial Of Two Interventions To Reduce Antibiotic Misuse, Kathy Goggin, Emily A. Hurley, Brian R. Lee, Andrea Bradley-Ewing, Carey Bickford, Kimberly Pina, Evelyn Donis De Miranda, David Yu, Kirsten Weltmer, Sebastian Linnemayr, Christopher C. Butler, Jason G. Newland, Angela L Myers

2020-Current year OA Pubs

BACKGROUND: Children with acute respiratory tract infections (ARTIs) receive ≈11.4 million unnecessary antibiotic prescriptions annually. A noted contributor is inadequate parent-clinician communication, however, efforts to reduce overprescribing have only indirectly targeted communication or been impractical.

OBJECTIVES: Compare two feasible (higher vs lower intensity) interventions for enhancing parent-clinician communication on the rate of inappropriate antibiotic prescribing.

DESIGN: Multisite, parallel group, cluster randomised comparative effectiveness trial. Data collected between March 2017 and March 2019.

SETTING: Academic and private practice outpatient clinics.

PARTICIPANTS: Clinicians (n=41, 85% of eligible approached) and 1599 parent-child dyads (ages 1-5 years with ARTI symptoms, 71% of eligible approached). …

Structural Basis Of Synthetic Agonist Activation Of The Nuclear Receptor Rev-Erb, Meghan H Murray, Aurore Cecile Valfort, Thomas Koelblen, Céline Ronin, Fabrice Ciesielski, Arindam Chatterjee, Giri Babu Veerakanellore, Bahaa Elgendy, John K Walker, Lamees Hegazy, Thomas P Burris

2020-Current year OA Pubs

The nuclear receptor REV-ERB plays an important role in a range of physiological processes. REV-ERB behaves as a ligand-dependent transcriptional repressor and heme has been identified as a physiological agonist. Our current understanding of how ligands bind to and regulate transcriptional repression by REV-ERB is based on the structure of heme bound to REV-ERB. However, porphyrin (heme) analogues have been avoided as a source of synthetic agonists due to the wide range of heme binding proteins and potential pleotropic effects. How non-porphyrin synthetic agonists bind to and regulate REV-ERB has not yet been defined. Here, we characterize a high affinity …

Return Of Non-Acmg Recommended Incidental Genetic Findings To Pediatric Patients: Considerations And Opportunities From Experiences In Genomic Sequencing, Kevin M Bowling, Michelle L Thompson, Melissa A Kelly, Sarah Scollon, Anne M Slavotinek, Bradford C Powell, Brian M Kirmse, Laura G Hendon, Kyle B Brothers, Bruce R Korf, Gregory M Cooper, John M Greally, Anna C E Hurst

2020-Current year OA Pubs

BACKGROUND: The uptake of exome/genome sequencing has introduced unexpected testing results (incidental findings) that have become a major challenge for both testing laboratories and providers. While the American College of Medical Genetics and Genomics has outlined guidelines for laboratory management of clinically actionable secondary findings, debate remains as to whether incidental findings should be returned to patients, especially those representing pediatric populations.

METHODS: The Sequencing Analysis and Diagnostic Yield working group in the Clinical Sequencing Evidence-Generating Research Consortium has collected a cohort of pediatric patients found to harbor a genomic sequencing-identified non-ACMG-recommended incidental finding. The incidental variants were not thought …