Rates of bronchopulmonary dysplasia in very low birth weight neonates: a systematic review and meta-analysis.

Importance: Large-scale estimates of bronchopulmonary dysplasia (BPD) are warranted for adequate prevention and treatment. However, systematic approaches to ascertain rates of BPD are lacking.

Objective: To conduct a systematic review and meta-analysis to assess the prevalence of BPD in very low birth weight (≤ 1,500 g) or very low gestational age (< 32 weeks) neonates.

Cefazolin vs Second-line Antibiotics for Surgical Site Infection Prevention After Total Joint Arthroplasty Among Patients With a Beta-lactam Allergy.

Background: Cefazolin is a first-line agent for prevention of surgical site infections (SSIs) after total joint arthroplasty. Patients labeled allergic to beta-lactam antibiotics frequently receive clindamycin or vancomycin perioperatively due to the perceived risk of a hypersensitivity reaction after exposure to cefazolin.

Methods: This single-system retrospective review included patients labeled allergic to penicillin or cephalosporin antibiotics who underwent a primary total hip and/or knee arthroplasty between January 2020 and July 2021.

Mixed-Reality Simulation for a Pediatric Transport Team: A Pilot Study.

Objective: Transport medicine requires a complex set of skills including fast-paced medical decision making, in-depth medical knowledge, procedural competence, interpersonal and communication skills, leadership, and professionalism. There has been a call for more training in these areas. Simulation-based training can be a way to acquire these necessary skills and bridge the gap to higher-quality transport care.

Intranasal delivery of human umbilical cord Wharton's jelly mesenchymal stromal cells restores lung alveolarization and vascularization in experimental bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a devastating lung condition that develops in premature newborns exposed to prolonged mechanical ventilation and supplemental oxygen. Significant morbidity and mortality are associated with this costly disease and effective therapies are limited. Mesenchymal stem/stromal cells (MSCs) are multipotent cells that can repair injured tissue by secreting paracrine factors known to restore the function and integrity of injured lung epithelium and endothelium.

Identification of Cosalane as an Inhibitor of Human and Murine CC-Chemokine Receptor 7 Signaling via a High-Throughput Screen.

CC-chemokine receptor 7 (CCR7) is a G protein-coupled receptor expressed on a variety of immune cells. CCR7 plays a critical role in the migration of lymphocytes into secondary lymphoid tissues. CCR7 expression, however, has been linked to numerous disease states.

Performing the Brain Death Examination and the Declaration of Pediatric Brain Death.

Declaration of brain death is a clinical diagnosis made by the absence of neurological function in a comatose patient secondary to a known irreversible cause. Brain death determination is not an infrequent process in pediatric intensive care units. It is important that pediatric intensive care providers understand the definition of brain death and intensivists are able to implement brain death testing.

A Novel Family of Small Molecules that Enhance the Intracellular Delivery and Pharmacological Effectiveness of Antisense and Splice Switching Oligonucleotides.

The pharmacological effectiveness of oligonucleotides has been hampered by their tendency to remain entrapped in endosomes, thus limiting their access to cytosolic or nuclear targets. We have previously reported a group of small molecules that enhance the effects of oligonucleotides by causing their release from endosomes. Here, we describe a second novel family of oligonucleotide enhancing compounds (OECs) that is chemically distinct from the compounds reported previously.

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children.

Background: Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited.

Methods: In a trial conducted at 37 children's hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.

Development of a Comprehensive Communication Skills Curriculum for Pediatrics Residents.

Background: Effective communication is an essential element of medical care and a priority of medical education. Specific interventions to teach communication skills are at the discretion of individual residency programs.

Objective: We developed the Resident Communication Skills Curriculum (RCSC), a formal curriculum designed to teach trainees the communication skills essential for high-quality practice.

Therapeutic hypothermia after out-of-hospital cardiac arrest in children.

Background: Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited.

Methods: We conducted this trial of two targeted temperature interventions at 38 children's hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.

Using simulation to address hierarchy-related errors in medical practice.

Objective: Hierarchy, the unavoidable authority gradients that exist within and between clinical disciplines, can lead to significant patient harm in high-risk situations if not mitigated. High-fidelity simulation is a powerful means of addressing this issue in a reproducible manner, but participant psychological safety must be assured. Our institution experienced a hierarchy-related medication error that we subsequently addressed using simulation.

Filtration improves the performance of a high-throughput screen for anti-mycobacterial compounds.

The tendency for mycobacteria to aggregate poses a challenge for their use in microplate based assays. Good dispersions have been difficult to achieve in high-throughput screening (HTS) assays used in the search for novel antibacterial drugs to treat tuberculosis and other related diseases. Here we describe a method using filtration to overcome the problem of variability resulting from aggregation of mycobacteria.

A simulation-based curriculum to address relational crises in medicine.

Introduction: Preparing health care professionals for challenging communication tasks such as delivering bad news to patients and families is an area where a need for improved teaching has been identified.

Objectives: We developed a simulation-based curriculum to enhance the skills of health care professionals, with an emphasis on the communication of difficult or bad news, which we termed relational crises.

Methods: Our approach was based on a review of existing simulation-based curricula, with the addition of unique features, including a learner-focused needs assessment to shape curriculum development, use of 360-degree evaluations, and provision of written feedback.

Development of a high-throughput assay for identifying inhibitors of TBK1 and IKKε.

IKKε and TBK1 are noncanonical IKK family members which regulate inflammatory signaling pathways and also play important roles in oncogenesis. However, few inhibitors of these kinases have been identified. While the substrate specificity of IKKε has recently been described, the substrate specificity of TBK1 is unknown, hindering the development of high-throughput screening technologies for inhibitor identification.

Inhibition of NFkappaB by the natural product Withaferin A in cellular models of Cystic Fibrosis inflammation.

Cystic Fibrosis (CF) is one of the most common autosomal genetic disorders in humans. This disease is caused by mutations within a single gene, coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The phenotypic hallmark of CF is chronic lung infection and associated inflammation from opportunistic microbes such as Pseudomonas aeruginosa (PA), Haemophilus influenzae, and Staphylococcus aureus.

Measurement of apoptosis and other forms of cell death.

As programmed cell death (PCD) or apoptosis has emerged as an important regulator of development and homeostasis in multicellular organisms, methods to quantify apoptosis and to distinguish it from necrosis have been developed. This unit presents a set of assays for these purposes, many of which are technically very simple and ideally suited to the study of hematopoietic cells. The first basic protocol allows the qualitative and quantitative assessment of apoptosis in lymphocyte cell cultures using light or fluorescent microscopy.

A Fas-associated death domain protein/caspase-8-signaling axis promotes S-phase entry and maintains S6 kinase activity in T cells responding to IL-2.

Fas-associated death domain protein (FADD) constitutes an essential component of TNFR-induced apoptotic signaling. Paradoxically, FADD has also been shown to be crucial for lymphocyte development and activation. In this study, we report that FADD is necessary for long-term maintenance of S6 kinase (S6K) activity.

The Low-Barrier Double-Well Potential of the O(δ)(1)-H-O(δ)(1) Hydrogen Bond in Unbound HIV Protease: A QM/MM Characterization.

The presence of a low-barrier hydrogen bond (LBHB) in aspartyl proteases and its implications in drug design have been the subject of intense study. Here, we present a combined quantum mechanical/molecular mechanical (QM/MM)-Numerov procedure and use it to characterize the O(δ)(1)-H-O(δ)(1) hydrogen bond (HB) in unbound HIV protease. The QM/MM scheme fully traces the shape of the HB's potential energy curve.

Hydrogen bonding is the prime determinant of carboxyl pKa values at the N-termini of alpha-helices.

Experimentally determined mean pK(a) values of carboxyl residues located at the N-termini of alpha-helices are lower than their overall mean values. Here, we perform three types of analyses to account for this phenomenon. We estimate the magnitude of the helix macrodipole to determine its potential role in lowering carboxyl pK(a) values at the N-termini.

Convergence of Ca2+-desensitizing mechanisms activated by forskolin and phenylephrine pretreatment, but not 8-bromo-cGMP.

Contractile stimuli can sensitize myosin to Ca2+ by activating RhoA kinase (ROK) and PKC that inhibit myosin light chain phosphatase (MLCP) activity. Relaxant stimuli, acting through PKA and PKG (cyclic nucleotide-dependent protein kinases), and pretreatment with contractile agents such as phenylephrine (PE), can desensitize myosin to Ca2+. It is unknown precisely how these stimuli cause Ca2+ desensitization.

Viral FLIP impairs survival of activated T cells and generation of CD8+ T cell memory.

Viral FLIPs (vFLIPs) interfere with apoptosis signaling by death-domain-containing receptors in the TNFR superfamily (death receptors). In this study, we show that T cell-specific transgenic expression of MC159-vFLIP from the human Molluscum contagiosum virus blocks CD95-induced apoptosis in thymocytes and peripheral T cells, but also impairs postactivation survival of in vitro activated primary T cells despite normal early activation parameters. MC159 vFLIP impairs T cell development to a lesser extent than does Fas-associated death domain protein deficiency or another viral FLIP, E8.

Death receptor signaling and autoimmunity.

In recent years, it has become clear that self-nonself discrimination by the immune system is driven not so much by the specificities of the antigen receptors themselves, but by ligand-receptor systems that sense the presence of foreign pathogens (toll-like receptors) and those that regulate the balance between cellular proliferation and programmed cell death (tumor necrosis factor [TNF] family ligands and receptors). Interestingly, these two receptor families share a number of common signaling pathways, mediated by the cytoplasmic proteins containing death domains and TRAF domains, which trigger the complementary processes of programmed cell death and inflammation. Both humans and mice with genetic defects in the TNF-receptor family member Fas accumulate abnormal lymphocytes and develop systemic autoimmunity.