Nanoengineered shear-thinning and bioprintable hydrogel as a versatile platform for biomedical applications.

The development of bioinks based on shear-thinning and self-healing hydrogels has recently attracted significant attention for constructing complex three-dimensional physiological microenvironments. For extrusion-based bioprinting, it is challenging to provide high structural reliability and resolution of printed structures while protecting cells from shear forces during printing. Herein, we present shear-thinning and printable hydrogels based on silicate nanomaterials, laponite (LA), and glycosaminoglycan nanoparticles (GAGNPs) for bioprinting applications.

Simulating a Transmission Assessment Survey: An evaluation of current methods used in determining the elimination of the neglected tropical disease, Lymphatic Filariasis.

Introduction: The World Health Organization (WHO) recommends Transmission Assessment Surveys (TAS) to determine when an evaluation unit (EU) (a designated population survey area) has achieved elimination of transmission of the vector-borne macroparasitic disease Lymphatic Filariasis (LF). These determinations are based on combining data from multiple survey units within an EU; it is unclear how underlying cluster-level variation influences the outcome of the TAS at EU level. We simulate LF infection distribution in an EU and compare three methods for assessing whether LF elimination has occurred based on currently recommended decision thresholds and sampling methods.

Supramolecular nanosubstrate-mediated delivery system enables CRISPR-Cas9 knockin of hemoglobin beta gene for hemoglobinopathies.

Leveraging the endogenous homology-directed repair (HDR) pathway, the CRISPR-Cas9 gene-editing system can be applied to knock in a therapeutic gene at a designated site in the genome, offering a general therapeutic solution for treating genetic diseases such as hemoglobinopathies. Here, a combined supramolecular nanoparticle (SMNP)/supramolecular nanosubstrate-mediated delivery (SNSMD) strategy is used to facilitate CRISPR-Cas9 knockin of the hemoglobin beta (HBB) gene into the adeno-associated virus integration site 1 (AAVS1) safe-harbor site of an engineered K562 3.21 cell line harboring the sickle cell disease mutation.

Flexible Multiplexed InO Nanoribbon Aptamer-Field-Effect Transistors for Biosensing.

Flexible sensors are essential for advancing implantable and wearable bioelectronics toward monitoring chemical signals within and on the body. Developing biosensors for monitoring multiple neurotransmitters in real time represents a key application that will increase understanding of information encoded in brain neurochemical fluxes. Here, arrays of devices having multiple InO nanoribbon field-effect transistors (FETs) were fabricated on 1.

Determinants of disease activity change over time in Enthesitis related arthritis: effect of structured outcome monitoring and clinical decision support.

Background: We aimed to test if standardized point-of-care outcome monitoring and clinical decision support (CDS), as compared to standard care, improves disease activity and patient-reported pain in children with enthesitis-related arthritis (ERA).

Methods: This was a retrospective cohort study of outcomes of children with ERA after phased implementation of I) standardized outcome monitoring with CDS for polyarticular JIA, and II) CDS for ERA, compared to a pre-intervention group of historical controls. We used multivariable mixed-effects models for repeated measures to test whether implementation phase or other disease characteristics were associated with change over time in disease activity, as measured by the clinical juvenile arthritis disease activity score (cJADAS), and pain.

Imaging in the diagnosis and management of axial spondyloarthritis in children.

Imaging is often used at the time of diagnosis to exclude conditions other than arthritis, to confirm the physical examination if equivocal, and to assess the degree of inflammation and baseline damage. Plain radiography is helpful in the evaluation of damage from chronic inflammation, while ultrasound and magnetic resonance imaging (MRI) are helpful in the assessment of early disease and active inflammation. Multiple studies have shown that tenderness on physical examination of the sacroiliac joint is often discordant with imaging results, so MRI is increasingly relied upon to assess for objective evidence of inflammation.

Calibrated Bayesian Credible Intervals for Binomial Proportions.

Drawbacks of traditional approximate (Wald test-based) and exact (Clopper-Pearson) confidence intervals for a binomial proportion are well-recognized. Alternatives include an interval based on inverting the score test, adaptations of exact testing, and Bayesian credible intervals derived from uniform or Jeffreys beta priors. We recommend a new interval intermediate between the Clopper-Pearson and Jeffreys in terms of both width and coverage.

Echocardiographic strain analysis reflects impaired ventricular function in youth with pediatric-onset systemic lupus erythematosus.

Background: Strain analysis with speckle-tracking echocardiography shows promise as a screening tool for silent myocardial dysfunction in pediatric-onset systemic lupus erythematosus (pSLE). We compared left ventricular (LV) systolic deformation (measured by strain) in children and adolescents with pSLE to controls, and assessed the relationship between strain, disease activity, and other noninvasive measures of cardiovascular health.

Methods: Twenty pSLE subjects ages 9-21 underwent comprehensive cardiovascular testing, including 2D speckle-tracking echocardiography, ambulatory blood pressure monitoring (ABPM), peripheral endothelial function testing, pulse wave velocity and analysis, and carotid ultrasound.

The history of workforce concerns in pediatric pulmonary Medicine.

Children are affected by a broad spectrum of acute and chronic respiratory disorders. The number of children with respiratory disease is increasing, as are the complexity of disease pathophysiology and the management demands on pediatric pulmonologists. Despite slowly increasing numbers of board-certified pediatric pulmonologists, large areas of the country are underserved and there is a perception of an impending workforce crisis.

Alterations of the salivary and fecal microbiome in patients with primary sclerosing cholangitis.

Background: Primary sclerosing cholangitis (PSC) is a chronic, progressive liver disease known for its frequent concurrence with inflammatory bowel disease. PSC can progress to cirrhosis, end-stage liver disease, hepatobiliary cancer, and/or colorectal cancer. The etiopathogenesis of PSC remains poorly understood, and, as such, pharmacotherapy has yet to be definitively established.

Lipid-Bicelle-Coated Microfluidics for Intracellular Delivery with Reduced Fouling.

Innovative technologies for intracellular delivery are ushering in a new era for gene editing, enabling the utilization of a patient's own cells for stem cell and immunotherapies. In particular, cell-squeezing platforms provide unconventional forms of intracellular delivery, deforming cells through microfluidic constrictions to generate transient pores and to enable effective diffusion of biomolecular cargo. While these devices are promising gene-editing platforms, they require frequent maintenance due to the accumulation of cellular debris, limiting their potential for reaching the throughputs necessary for scalable cellular therapies.

Reliability and validity of pediatric powered mobility outcome measures.

Purpose: To determine the intra-rater and inter-rater reliability of the Powered Mobility Program (PMP) and the Israel Ministry of Health Powered Mobility Proficiency Test (PM-PT); to test inter-rater reliability of the Assessment of Learning Powered Mobility (ALP) tool; to determine the convergent validity of these measures for children with physical disabilities.

Materials And Methods: Participants included 30 children (mean 10 years, 6 months [SD 3 years, 7 months]; range: 6-18 years) with cerebral palsy and other neuromuscular disorders. Participants were non-proficient powered wheelchair drivers.

Juvenile Spondyloarthritis: focus on uveitis.

Background: Juvenile spondyloarthritis (JSpA) represents a group of inflammatory arthritides with several distinctive features (enthesitis, involvement of spine and sacroiliac joint, HLA-B27 association and development of uveitis). There are limited data on the course of uveitis in children with JSpA. This study aims to estimate the prevalence of uveitis and to look at the presence of HLA-B27 in relation to uveitis occurrence and ocular symptoms in a cohort of JSpA patients.

In Situ Forming, Silanized Hyaluronic Acid Hydrogels with Fine Control Over Mechanical Properties and In Vivo Degradation for Tissue Engineering Applications.

In situ forming hydrogels that can be injected into tissues in a minimally-invasive fashion are appealing as delivery vehicles for tissue engineering applications. Ideally, these hydrogels should have mechanical properties matching those of the host tissue, and a rate of degradation adapted for neo-tissue formation. Here, the development of in situ forming hyaluronic acid hydrogels based on the pH-triggered condensation of silicon alkoxide precursors into siloxanes is reported.

Cloaking Silica Nanoparticles with Functional Protein Coatings for Reduced Complement Activation and Cellular Uptake.

Silica-coated nanoparticles are widely used in biomedical applications such as theranostics, imaging, and drug delivery. While silica-coated nanoparticles are biocompatible, experimental evidence shows that they can trigger innate immune reactions, and a broader understanding of what types of reactions are caused and how to mitigate them is needed. Herein, we investigated how the noncovalent surface functionalization of silica nanoparticles with purified proteins can inhibit nanoparticle-induced complement activation and macrophage uptake, two of the most clinically relevant innate immune reactions related to nanomedicines.

Agreement of Program Directors With Clinical Competency Committees for Fellow Entrustment.

Objectives: Fellowship program directors (FPD) and Clinical Competency Committees (CCCs) both assess fellow performance. We examined the association of entrustment levels determined by the FPD with those of the CCC for 6 common pediatric subspecialty entrustable professional activities (EPAs), hypothesizing there would be strong correlation and minimal bias between these raters.

Methods: The FPDs and CCCs separately assigned a level of supervision to each of their fellows for 6 common pediatric subspecialty EPAs.

Versatile lysine dendrigrafts and polyethylene glycol hydrogels with inherent biological properties: in vitro cell behavior modulation and in vivo biocompatibility.

Poly(ethylene glycol) (PEG) hydrogels have been extensively used as scaffolds for tissue engineering applications, owing to their biocompatibility, chemical versatility, and tunable mechanical properties. However, their bio-inert properties require them to be associated with additional functional moieties to interact with cells. To circumvent this need, we propose here to reticulate PEG molecules with poly(L-lysine) dendrigrafts (DGL) to provide intrinsic cell functionalities to PEG-based hydrogels.

Development of a Rat Model of Mandibular Irradiation Sequelae for Preclinical Studies of Bone Repair.

Repairing mandibular bone defects after radiotherapy of the upper aerodigestive tract is clinically challenging. Although bone tissue engineering has recently generated a number of innovative treatment approaches for osteoradionecrosis (ORN), these modalities must be evaluated preclinically in a relevant, reproducible, animal model. The objective of this study was to evaluate a novel rat model of mandibular irradiation sequelae, with a focus on the adverse effects of radiotherapy on bone structure, intraosseous vascularization, and bone regeneration.

Detecting DNA and RNA and Differentiating Single-Nucleotide Variations via Field-Effect Transistors.

We detect short oligonucleotides and distinguish between sequences that differ by a single base, using label-free, electronic field-effect transistors (FETs). Our sensing platform utilizes ultrathin-film indium oxide FETs chemically functionalized with single-stranded DNA (ssDNA). The ssDNA-functionalized semiconducting channels in FETs detect fully complementary DNA sequences and differentiate these sequences from those having different types and locations of single base-pair mismatches.