Publications by authors named "Aaron S Miller"

Importance: There is limited evidence for therapeutic options for pediatric COVID-19 outside of multisystem inflammatory syndrome in children (MIS-C).

Objective: To determine whether the use of steroids within 2 days of admission for non-MIS-C COVID-19 in children is associated with hospital length of stay (LOS). The secondary objective was to determine their association with intensive care unit (ICU) LOS, inflammation, and fever defervescence.

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Despite clear testing recommendations for herpes simplex virus (HSV) infection in infants, few data exist on the comprehensiveness of HSV testing in practice. In a 23-center study of 112 infants with confirmed HSV disease, less than one-fifth had all recommended testing performed, highlighting the need for increased awareness of and adherence to testing recommendations for this vulnerable population.

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Objectives: Suggested therapeutic options for Multisystem Inflammatory Syndrome in Children (MIS-C) include intravenous immunoglobulins (IVIG) and steroids. Prior studies have shown the benefit of combination therapy with both agents on fever control or the resolution of organ dysfunction. The primary objective of this study was to analyze the impact of IVIG and steroids on hospital and ICU length of stay (LOS) in patients with MIS-C associated with Coronavirus Disease 2019 (COVID-19).

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Objectives: To identify independent predictors of and derive a risk score for invasive herpes simplex virus (HSV) infection.

Methods: In this 23-center nested case-control study, we matched 149 infants with HSV to 1340 controls; all were ≤60 days old and had cerebrospinal fluid obtained within 24 hours of presentation or had HSV detected. The primary and secondary outcomes were invasive (disseminated or central nervous system) or any HSV infection, respectively.

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Objectives: Multicenter data on the characteristics and outcomes of children hospitalized with coronavirus disease 2019 are limited. Our objective was to describe the characteristics, ICU admissions, and outcomes among children hospitalized with coronavirus disease 2019 using Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 registry.

Design: Retrospective study.

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In our cohort of 20,947 infants aged 60 days or younger, cerebrospinal fluid Gram stain had a sensitivity of 34.3% (95% confidence interval, 28.1%-41.

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Background: Although neonatal herpes simplex virus (HSV) is a potentially devastating infection requiring prompt evaluation and treatment, large-scale assessments of the frequency in potentially infected infants have not been performed.

Methods: We performed a retrospective cross-sectional study of infants ≤60 days old who had cerebrospinal fluid culture testing performed in 1 of 23 participating North American emergency departments. HSV infection was defined by a positive HSV polymerase chain reaction or viral culture.

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Drozitumab is an agonistic therapeutic monoclonal antibody (mAb) against the pro-apoptotic death receptor 5 (DR5). In vitro cell killing assays using drozitumab have traditionally required cross-linking with anti-Fc antibody to amplify the pro-apoptotic signal, although drozitumab shows activity in in vivo tumor models without artificial cross-linking. Recently it has been shown that FcγR expressing cells play an important role in the activity of drozitumab by mediating cross-linking in vivo (Wilson et al.

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To determine age-stratified prevalence of concomitant bacterial meningitis in infants ≤60 days with a urinary tract infection, we performed a 23-center, retrospective study of 1737 infants with urinary tract infection. Concomitant bacterial meningitis was rare, but more common in infants 0-28 days of age [0.9%; 95% confidence interval (CI): 0.

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Objective. For decades, Haitian migrant workers living in bateyes around La Romana, Dominican Republic, have been the focus of short-term volunteer medical groups from North America. To assist these efforts, this study aimed to characterize various health and social needs that could be addressed by volunteer groups.

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Objective: To inform the decision to test and empirically treat for herpes simplex virus (HSV) by describing the initial clinical presentation and laboratory findings of infants with a confirmed diagnosis of neonatal HSV.

Study Design: This is a retrospective case series performed at 2 pediatric tertiary care centers. Infants who developed symptoms prior to 42 days of age with laboratory confirmed HSV from 2002 through 2012 were included.

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Objectives: Afebrile infants 0 to 60 days of age are sometimes evaluated for serious bacterial infection (SBI). Our objective was to describe the clinical and laboratory findings in this population and compare them to their febrile counterparts.

Methods: We performed a retrospective observational study comparing afebrile infants undergoing an SBI evaluation to those evaluated for fever.

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Background And Objectives: Herpes simplex virus (HSV) is rare in neonates but carries significant morbidity and mortality in that group. Emergency department (ED) clinicians have little guidance to decide when to test for HSV and give acyclovir. We created an institutional guideline to provide guidance in patients younger than 6 weeks.

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Effective chronic disease management is essential to improve positive health outcomes, and incentive strategies are useful in promoting self-care with longevity. Gamification, applied with mHealth (mobile health) applications, has the potential to better facilitate patient self-management. This review article addresses a knowledge gap around the effective use of gamification design principles, or mechanics, in developing mHealth applications.

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Antibody-dependent cell-mediated cytotoxicity (ADCC) is a relevant characteristic to measure for a number of therapeutic monoclonal antibodies (mAbs) under development. ADCC is a mechanism by which antibody-opsonized, infected, or cancerous cells are destroyed by FcγRIII (CD16)-expressing effector cells. Here we describe three methods that can be used to quantify the ADCC activity of mAbs by measuring distinct aspects of the ADCC mechanism.

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Antibody dependent cell-mediated cytotoxicity (ADCC) is an important mechanism of action (MoA) for many monoclonal antibody (mAb) therapeutics. As such, quantitative measurement of ADCC activity is key to drug development. Traditional cell lysis based ADCC assays using PBMCs or NK cell lines can be challenging to develop and implement for routine testing.

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Histidine-rich protein II (HRPII) is an abundant protein released into the bloodstream by Plasmodium falciparum, the parasite that causes the most severe form of human malaria. Here, we report that HRPII binds tightly and selectively to coagulation-active glycosaminoglycans (dermatan sulfate, heparan sulfate, and heparin) and inhibits antithrombin (AT). In purified systems, recombinant HRPII neutralized the heparin-catalyzed inhibition of factor Xa and thrombin by AT in a Zn(2+)-dependent manner.

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The number of known protein structures is growing exponentially (Berman et al., 2000), but the structural mapping of essential domain-domain and protein-protein interaction surfaces has advanced more slowly. It is particularly difficult to analyze the interaction surfaces of membrane proteins on a structural level, both because membrane proteins are less accessible to high-resolution structural analysis and because the membrane environment is often required for native complex formation.

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Salmonella species are a common cause of enteritis and other focal infections, including osteomyelitis, septic arthritis, and abscess. We report a case of ovarian abscess caused by nontyphoidal Salmonella in an adolescent girl. Pediatricians, infectious diseases specialists, and surgical consultants should consider this entity within the differential diagnoses of lower quadrant pain and adnexal mass in adolescent females.

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The chemotaxis pathway of Escherichia coli and Salmonella typhimurium is the paradigm for the ubiquitous class of 2-component signaling pathways in prokaryotic organisms. Chemosensing begins with the binding of a chemical attractant to a transmembrane receptor on the cell surface. The resulting transmembrane signal regulates a cytoplasmic, multiprotein signaling complex that controls cellular swimming behavior by generating a diffusible phosphoprotein.

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Previous model studies of peptides and proteins have shown that protein-lipid interactions, primarily involving amino acid side chains near the membrane-water interface, modulate the position of transmembrane helices in bilayers. The present study examines whether such interfacial side chains stabilize the signaling states of a transmembrane signaling helix in a representative receptor, the aspartate receptor of bacterial chemotaxis. To examine the functional roles of signaling helix side chains at the periplasmic and cytoplasmic membrane-water interfaces, arginine and cysteine substitutions were scanned through these two interfacial regions.

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