Cationic Polystyrene Latex Nanocarriers for Immunostimulatory Long Double-Stranded RNA Delivery to Ovarian Cancer Cells.

Long double-stranded (ds)RNA, a potent stimulator of type I interferon and the innate immune response. In the present study, we demonstrated, for the first time, the efficacy of cationic polystyrene latex nanostructures (clNPs) as a dsRNA carrier, improving cellular delivery and robustly potentiating the immunostimulatory capacity of dsRNA in the ovarian cancer cell line SKOV3. The clNPs complexed with an in vitro transcribed dsRNA molecule, were bound by SKOV3 cells, and had increased cellular association compared to uncomplexed clNPs.

Evaluating Cationic Nanoparticles as Carriers of Antiviral Nucleic Acids.

Nanoparticle carriers enable the multivalent delivery of nucleic acids to cells and protect them from degradation. In this chapter, we present a comprehensive overview of four methodologies: electrophoretic mobility shift assay (EMSA), alamarBlue/CFDA-AM cell viability dyes, fluorescence microscopy, and antiviral assays, which collectively are tools to explore interactions between nucleic acids and nanoparticles, and their biological efficacy. These assays provide insights into binding potential, cytotoxicity, and antiviral efficacy of nucleic acid-based nanoparticle treatments furthering the development of effective antiviral therapeutics.

Integrating education for clinical practice change.

Background: Children with chronic medical conditions and their families have significant emotional health concerns, yet paediatricians are often ill-equipped to address these needs. The American Board of Pediatrics launched the Roadmap Project to better support emotional health as part of routine care. We present pilot work in paediatric training programmes to test educational approaches and explore lessons learned.

TAK-242 treatment and its effect on mechanical properties and gene expression associated with IVD degeneration in SPARC-null mice.

Purpose: Intervertebral disc (IVD) degeneration is accompanied by mechanical and gene expression changes to IVDs. SPARC-null mice display accelerated IVD degeneration, and treatment with (toll-like receptor 4 (TLR4) inhibitor) TAK-242 decreases proinflammatory cytokines and pain. This study examined if chronic TAK-242 treatment impacts mechanical properties and gene expression associated with IVD degeneration in SPARC-null mice.

The Impact of a Gamified Curriculum Using Kahoot! on Musculoskeletal Knowledge and Skill Acquisition Among Pediatric Residents.

Objective: To determine whether a musculoskeletal curriculum involving gamification via Kahoot! (an online classroom response system) was acceptable and more effective at teaching pediatric residents musculoskeletal knowledge and skills than a nongamified curriculum.

Methods: A prospective, randomized controlled trial was conducted at an urban, academic pediatric clinic. All participants received a curriculum that included brief didactics and knowledge questions.

Effect of a Novel Mindfulness Curriculum on Burnout During Pediatric Internship: A Cluster Randomized Clinical Trial.

Importance: Mindfulness curricula can improve physician burnout, but implementation during residency presents challenges.

Objective: To examine whether a novel mindfulness curriculum implemented in the first 6 months of internship reduces burnout.

Design, Setting, And Participants: This pragmatic, multicenter, stratified cluster randomized clinical trial of a mindfulness curriculum randomized 340 pediatric interns to the intervention or control arm within program pairs generated based on program size and region.

The deployment of mobile diagnostic laboratories for Ebola virus disease diagnostics in Sierra Leone and Guinea.

Background: Ebola virus emerged in West Africa in December 2013. The ease of mobility, porous borders, and lack of public health infrastructure led to the largest Ebola virus disease (EVD) outbreak to date.

Intervention: The 2013 EVD outbreak signalled the need for laboratory diagnostic capabilities in areas without strong public health systems.

Sustainable Laboratory Capacity Building After the 2014 Ebola Outbreak in the Republic of Guinea.

The 2014-2016 West Africa Ebola virus disease outbreak heavily impacted the Republics of Guinea, Sierra Leone, and Liberia. The outbreak uncovered the weaknesses of the public health systems, including inadequately trained and insufficient health personnel as well as limited and poorly equipped health infrastructures. These weaknesses represent significant threats to global health security.

Extended Work Shifts and Neurobehavioral Performance in Resident-Physicians.

Objectives: Extended-duration work rosters (EDWRs) with shifts of 24+ hours impair performance compared with rapid cycling work rosters (RCWRs) that limit shifts to 16 hours in postgraduate year (PGY) 1 resident-physicians. We examined the impact of a RCWR on PGY 2 and PGY 3 resident-physicians.

Methods: Data from 294 resident-physicians were analyzed from a multicenter clinical trial of 6 US PICUs.

Pediatric Resident Engagement With an Online Critical Care Curriculum During the Intensive Care Rotation.

Objectives: Residents are often assigned online learning materials as part of blended learning models, superimposed on other patient care and learning demands. Data that describe the time patterns of when residents interact with online learning materials during the ICU rotation are lacking. We describe resident engagement with assigned online curricula related to time of day and ICU clinical schedules, using website activity data.

Effect on Patient Safety of a Resident Physician Schedule without 24-Hour Shifts.

Background: The effects on patient safety of eliminating extended-duration work shifts for resident physicians remain controversial.

Methods: We conducted a multicenter, cluster-randomized, crossover trial comparing two schedules for pediatric resident physicians during their intensive care unit (ICU) rotations: extended-duration work schedules that included shifts of 24 hours or more (control schedules) and schedules that eliminated extended shifts and cycled resident physicians through day and night shifts of 16 hours or less (intervention schedules). The primary outcome was serious medical errors made by resident physicians, assessed by intensive surveillance, including direct observation and chart review.

Use of Resident-Sensitive Quality Measure Data in Entrustment Decision Making: A Qualitative Study of Clinical Competency Committee Members at One Pediatric Residency.

Purpose: Resident-sensitive quality measures (RSQMs) are quality measures that are likely performed by an individual resident and are important to care quality for a given illness of interest. This study sought to explore how individual clinical competency committee (CCC) members interpret, use, and prioritize RSQMs alongside traditional assessment data when making a summative entrustment decision.

Method: In this constructivist grounded theory study, 19 members of the pediatric residency CCC at Cincinnati Children's Hospital Medical Center were purposively and theoretically sampled between February and July 2019.

Narrative Performance Level Assignments at Initial Entrustment and Graduation: Integrating EPAs and Milestones to Improve Learner Assessment.

Purpose: To determine which narrative performance level for each general pediatrics entrustable professional activity (EPA) reflects the minimum level clinical competency committees (CCCs) felt should be associated with graduation as well as initial entrustment and compare expected narrative performance levels (ENPLs) for each EPA with actual narrative performance levels (ANPLs) assigned to residents at initial entrustment.

Method: A series of 5 narratives, corresponding to the 5 milestone performance levels, were developed for each of the 17 general pediatrics EPAs. In academic year (AY) 2015-2016, the CCCs at 22 Association of Pediatric Program Directors Longitudinal Educational Assessment Research Network member sites reported ENPLs for initial entrustment and at time of graduation.

Two DExD/H-box helicases, DDX3 and DHX9, identified in rainbow trout are able to bind dsRNA.

In mammals, the multifunctional DExH/D-box helicases, DDX3 and DHX9, are nucleic acid sensors with a role in antiviral immunity; their role in innate immunity in fish is not yet understood. In the present study, full-length DDX3 and DHX9 coding sequences were identified in rainbow trout (Oncorhynchus mykiss). Bioinformatic analysis demonstrated both deduced proteins were similar to those of other species, with ~80% identity to other fish species and ~70-75% identity to mammals, and both protein sequences had conserved domains found amongst all species.

Effects on resident work hours, sleep duration, and work experience in a randomized order safety trial evaluating resident-physician schedules (ROSTERS).

Study Objectives: We compared resident physician work hours and sleep in a multicenter clustered-randomized crossover clinical trial that randomized resident physicians to an Extended Duration Work Roster (EDWR) with extended-duration (≥24 hr) shifts or a Rapidly Cycling Work Roster (RCWR), in which scheduled shift lengths were limited to 16 or fewer consecutive hours.

Methods: Three hundred two resident physicians were enrolled and completed 370 1 month pediatric intensive care unit rotations in six US academic medical centers. Sleep was objectively estimated with wrist-worn actigraphs.

Design and recruitment of the randomized order safety trial evaluating resident-physician schedules (ROSTERS) study.

Introduction: While the Accreditation Council for Graduate Medical Education limited first year resident-physicians to 16 consecutive work hours from 2011 to 2017, resident-physicians in their second year or higher were permitted to work up to 28 h consecutively. This paper describes the Randomized Order Safety Trial Evaluating Resident-physician Schedules (ROSTERS) study, a clustered-randomized crossover clinical trial designed to evaluate the effectiveness of eliminating traditional shifts of 24 h or longer for second year or higher resident-physicians in pediatric intensive care units (PICUs).

Methods: ROSTERS was a multi-center non-blinded trial in 6 PICUs at US academic medical centers.

Justifications for Discrepancies Between Competency Committee and Program Director Recommended Resident Supervisory Roles.

Objective: To explore justifications for differences between summative entrustment decisions made about pediatric residents by individuals who are charged with the review of residents (clinical competency committee, or CCC, members) and those who ultimately make final summative decisions about resident performance (program directors, or PDs).

Methods: Individual CCC member and PD supervisory role categorizations were made in the 2015 to 2016 academic year at 14 pediatric residency programs, placing residents into 1 of 5 progressive supervisory roles. When PD recommendations differed from CCC members, a free-text justification was requested.

In vitro transcribed dsRNA limits viral hemorrhagic septicemia virus (VHSV)-IVb infection in a novel fathead minnow (Pimephales promelas) skin cell line.

The farming of baitfish, fish used by anglers to catch predatory species, is of economic and ecological importance in North America. Baitfish, including the fathead minnow (Pimephales promelas), are susceptible to infection from aquatic viruses, such as viral hemorrhagic septicemia virus (VHSV). VHSV infections can cause mass mortality events and have the potential to be spread to novel water bodies through baitfish as a vector.

Modular Organization and Assembly of SWI/SNF Family Chromatin Remodeling Complexes.

Mammalian SWI/SNF (mSWI/SNF) ATP-dependent chromatin remodeling complexes are multi-subunit molecular machines that play vital roles in regulating genomic architecture and are frequently disrupted in human cancer and developmental disorders. To date, the modular organization and pathways of assembly of these chromatin regulators remain unknown, presenting a major barrier to structural and functional determination. Here, we elucidate the architecture and assembly pathway across three classes of mSWI/SNF complexes-canonical BRG1/BRM-associated factor (BAF), polybromo-associated BAF (PBAF), and newly defined ncBAF complexes-and define the requirement of each subunit for complex formation and stability.

Extracellular dsRNA induces a type I interferon response mediated via class A scavenger receptors in a novel Chinook salmon derived spleen cell line.

Despite increased global interest in Chinook salmon aquaculture, little is known of their viral immune defenses. This study describes the establishment and characterization of a continuous cell line derived from Chinook salmon spleen, CHSS, and its use in innate immune studies. Optimal growth was seen at 14-18 °C when grown in Leibovitz's L-15 media with 20% fetal bovine serum.

Understanding Viral dsRNA-Mediated Innate Immune Responses at the Cellular Level Using a Rainbow Trout Model.

Viruses across genome types produce long dsRNA molecules during replication [viral (v-) dsRNA]. dsRNA is a potent signaling molecule and inducer of type I interferon (IFN), leading to the production of interferon-stimulated genes (ISGs), and a protective antiviral state within the cell. Research on dsRNA-induced immune responses has relied heavily on a commercially available, and biologically irrelevant dsRNA, polyinosinic:polycytidylic acid (poly I:C).

A novel workplace-based assessment for competency-based decisions and learner feedback.

Background: Increased recognition of the importance of competency-based education and assessment has led to the need for practical and reliable methods to assess relevant skills in the workplace.

Methods: A novel milestone-based workplace assessment system was implemented in 15 pediatrics residency programs. The system provided: (1) web-based multisource feedback (MSF) and structured clinical observation (SCO) instruments that could be completed on any computer or mobile device; and (2) monthly feedback reports that included competency-level scores and recommendations for improvement.