Glucose and Oxygen Levels Modulate the Pore-Forming Effects of Cholesterol-Dependent Cytolysin Pneumolysin from .

A major pathogenic factor is the cholesterol-dependent cytolysin pneumolysin, binding membrane cholesterol and producing permanent lytic or transient pores. During brain infections, vascular damage with variable ischemia occurs. The role of ischemia on pneumolysin's pore-forming capacity remains unknown.

The use of ketorolac may reduce opioid exposure in infants less than 6 months of age undergoing congenital heart surgery.

Objectives: Pain management for infants undergoing cardiothoracic surgery primarily utilises opioid analgesics. There is a paucity of data available for the use of non-steroidal anti-inflammatory medications such as ketorolac in this patient population.

Materials And Methods: This retrospective study evaluated patients between 30 days and 6 months undergoing cardiothoracic surgery.

Cardiac Critical Care Fellowship Training in the United States and Canada: Pediatric Cardiac Intensive Care Society-Endorsed Subcompetencies to the 2022 Entrustable Professional Activities.

Objectives: We aimed to define and map subcompetencies required for pediatric cardiac critical care (PCCC) fellowship education and training under the auspices of the Pediatric Cardiac Intensive Care Society (PCICS). We used the 2022 frameworks for PCCC fellowship learning objectives by Tabbutt et al and for entrustable professional activities (EPAs) by Werho et al and integrated new subcompetencies to the EPAs. This complementary update serves to provide a foundation for standardized trainee assessment tools for PCCC.

Dendritic spine loss deep in the neocortex and dendrite distortion with diffusion disturbances occur early in experimental pneumococcal meningitis.

Introduction: (pneumococcus) meningitis is a serious disease with substantial lethality and long-term disability in survivors. Loss of synaptic staining in the superficial layers of the neocortex in rodent models and in humans, and pneumolysin (a major pneumococcal toxin)-dependent dendritic spine collapse in brain slices have been described. It remains unclear how deep in the neocortex more discrete changes are present, how soon after disease onset these changes occur, and whether other properties of dendrites are also affected.

Meningitis-associated pneumococcal serotype 8, ST 53, strain is hypervirulent in a rat model and has non-haemolytic pneumolysin which can be attenuated by liposomes.

Introduction: bacteria cause life-threatening invasive pneumococcal disease (IPD), including meningitis. Pneumococci are classified into serotypes, determined by differences in capsular polysaccharide and both serotype and pneumolysin toxin are associated with disease severity. Strains of serotype 8, ST 53, are increasing in prevalence in IPD in several countries.

The lived experiences of health science graduate students with anxiety and depression.

Health science graduate programs are intensive experiences in students' lives which can contribute to perceived symptoms of anxiety and/or depression. The consequent impact of these symptoms can have an overall effect on the graduate students' ability to participate in their daily lives, along with their program of study. The purpose of this study was to understand the lived experiences of health science graduate students who experience perceived signs and symptoms of anxiety and/or depression.

Pneumolysin boosts the neuroinflammatory response to Streptococcus pneumoniae through enhanced endocytosis.

In pneumococcal meningitis, bacterial growth in the cerebrospinal fluid results in lysis, the release of toxic factors, and subsequent neuroinflammation. Exposure of primary murine glia to Streptococcus pneumoniae lysates leads to strong proinflammatory cytokine and chemokine production, blocked by inhibition of the intracellular innate receptor Nod1. Lysates enhance dynamin-dependent endocytosis, and dynamin inhibition reduces neuroinflammation, blocking ligand internalization.

A comparison of high-flow nasal cannula versus non-invasive positive pressure ventilation for respiratory support in infants following cardiac surgery.

Background: Following cardiac surgery, infants often remain endotracheally intubated upon arrival to the cardiac ICU. High-flow nasal cannula and non-invasive positive pressure ventilation are used to support patients following extubation. There are limited data on the superiority of either mode to prevent extubation failure.

Acceptability of an mHealth App for Youth With Substance Use and Mental Health Needs: Iterative, Mixed Methods Design.

Background: Treating substance use disorders (SUDs) during adolescence can prevent adult addiction and improve youth outcomes. However, it can be challenging to keep adolescents with SUDs engaged in ongoing services, thus limiting potential benefits. Developmentally appropriate tools are needed to improve treatment engagement during and between sessions for youth with SUDs and mental health disorders.

Easy to build cost-effective acute brain slice incubation system for parallel analysis of multiple treatment conditions.

Background: Acute brain slices represent a powerful tool for analysis of brain function in physiology and pathology. Commercial systems and custom-build solutions with carbogen (95% O/5% CO) aeration, but they are expensive, have a high working volume requiring large amount of substances, and only limited options for treatment in parallel are possible.

New Method: We developed a novel cost-effective incubation system using materials available in every laboratory, allowing parallel incubation of several treatment conditions, thus also reducing the number of experimental animals.

CSF-1 receptor inhibition as a highly effective tool for depletion of microglia in mixed glial cultures.

Background: A breakthrough in the microglia and macrophages field was the identification of the macrophage colony stimulating factor-1 (CSF-1) as a pro-survival factor. Its pharmacological inhibition in animals depletes rapidly all microglia and macrophages. Microglial depletion in mixed glial cultures has always represented a challenge and none of the existing approaches delivers satisfactory results.

Noninvasive Phenotyping of Plant-Pathogen Interaction: Consecutive Imaging of Fluorescing , Plant Phenolic Fluorescence, and Chlorophyll Fluorescence in Leaves.

Plant-pathogen interactions have been widely studied, but mostly from the site of the plant secondary defense. Less is known about the effects of pathogen infection on plant primary metabolism. The possibility to transform a fluorescing protein into prokaryotes is a promising phenotyping tool to follow a bacterial infection in plants in a noninvasive manner.

Natriuretic Peptides Attenuate Retinal Pathological Neovascularization Via Cyclic Guanosine Monophosphate Signaling in Pericytes and Astrocytes.

Objective: In proliferative retinopathies, complications derived from neovascularization cause blindness. During early disease, pericyte's apoptosis contributes to endothelial dysfunction and leakage. Hypoxia then drives VEGF (vascular endothelial growth factor) secretion and pathological neoangiogenesis.

Successful Use of Pulmonary Cryotherapy for Tracheobronchial Thrombus Extraction and Recanalization of the Tracheobronchial Tree During a Pediatric Venovenous Extracorporeal Membrane Oxygenation Run.

Impacted pediatric tracheobronchial thrombus is an uncommon diagnosis. There are no clearly proven therapeutic options for airway casts due to a similar process, plastic bronchitis. Cryotherapy, specifically cryoextraction, has shown potential as a therapeutic option in adults with tracheobronchial thrombus and cast.

Risk of development of treated retinopathy of prematurity in very low birth weight infants.

Objective: Quantify the risk of treatment for retinopathy of prematurity (ROP) among infants meeting current U.S. screening guidelines.

Pneumolysin and the bacterial capsule of Streptococcus pneumoniae cooperatively inhibit taxis and motility of microglia.

Background: Streptococcus pneumoniae is the cause of a highly lethal form of meningitis in humans. Microglial cells in the brain represent the first line of defense against pathogens, and they participate in the inflammatory response. The cholesterol-dependent cytolysin pneumolysin and the bacterial capsule are key pathogenic factors, known to exacerbate the course of pneumococcal meningitis.

Correlation Among Antifactor Xa, Activated Partial Thromboplastin Time, and Heparin Dose and Association with Pediatric Extracorporeal Membrane Oxygenation Complications.

Anticoagulation is essential during extracorporeal membrane oxygenation (ECMO) to prevent catastrophic circuit clotting. Several assays exist to monitor unfractionated heparin (UFH), the most commonly used anticoagulant during ECMO, but no single test or combination of tests has consistently been proven to be superior. This retrospective observational study examines the correlation among antifactor Xa level, activated partial thromboplastin time (aPTT), and UFH dose and the association between antifactor Xa level and aPTT with survival and hemorrhagic and thrombotic complications.

Missing elimination via membrane vesicle shedding contributes to the diminished calcium sensitivity of listeriolysin O.

The lytic capacity of cholesterol-dependent cytolysins is enhanced in the extracellular calcium-free environment through a combination of limited membrane repair and diminished membrane toxin removal. For a typical neurotoxin of the group, pneumolysin, this effect has already been observed at reduced (1 mM) calcium conditions, which are pathophysiologically relevant. Here, we tested another neurotoxin of the group, listeriolysin O from L.

Effects of Methadone on Corrected Q-T Interval Prolongation in Critically Ill Children.

Objectives: This study aimed to determine the association between methadone use and corrected Q-T interval (QTc) prolongation in critically ill children.

Methods: A retrospective cohort study of critically ill children receiving methadone at a tertiary care pediatric hospital was conducted. Patients younger than 19 years who had been admitted to the intensive care unit between January 1, 2009, and June 21, 2013, who had received methadone while inpatients, and who had had electrocardiograms (ECGs) performed within 30 days before and after methadone initiation were included.

Magnesium therapy improves outcome in Streptococcus pneumoniae meningitis by altering pneumolysin pore formation.

Background And Purpose: Streptococcus pneumoniae is the most common cause of bacterial meningitis in adults and is characterized by high lethality and substantial cognitive disabilities in survivors. Here, we have studied the capacity of an established therapeutic agent, magnesium, to improve survival in pneumococcal meningitis by modulating the neurological effects of the major pneumococcal pathogenic factor, pneumolysin.

Experimental Approach: We used mixed primary glial and acute brain slice cultures, pneumolysin injection in infant rats, a mouse meningitis model and complementary approaches such as Western blot, a black lipid bilayer conductance assay and live imaging of primary glial cells.

The use of pulmonary clearance medications in the acutely ill patient.

Retention of airway secretions occurs in disease, leading to airway plugging, atelectasis, and worsened respiratory mechanics, making airway clearance an important therapeutic target. Areas covered: Many medications designed to enhance clearance of airway secretions are available. We will review the medications available to enhance airway clearance, their mechanisms of action, and the evidence available for their use in acutely ill patients.

Use of a Modified Classic BT Shunt in a Patient With Multiple Conduit Obstructions With Positive Lupus Anticoagulant.

The use of a right ventricle-to-pulmonary artery conduit has re-emerged as a popular alternative to a systemic artery-to-pulmonary artery shunt in the Norwood procedure. Both proximal obstruction secondary to dynamic compression and distal obstruction at the anastomosis site with the pulmonary arteries are well described. In an effort to prevent complications, a technique where in the conduit is placed through the entire full thickness, or dunked, through the RV free wall has been described.

Distinct Neurotoxicity Profile of Listeriolysin O from Listeria monocytogenes.

Cholesterol-dependent cytolysins (CDCs) are protein toxins that originate from Gram-positive bacteria and contribute substantially to their pathogenicity. CDCs bind membrane cholesterol and build prepores and lytic pores. Some effects of the toxins are observed in non-lytic concentrations.

Pharmacokinetics and Safety of Micafungin in Infants Supported With Extracorporeal Membrane Oxygenation.

Background: Candida is a leading cause of infection in infants on extracorporeal membrane oxygenation (ECMO). Optimal micafungin dosing is unknown in this population because ECMO can alter drug pharmacokinetics (PK).

Methods: To characterize micafungin pharmacokinetics and safety in infants on ECMO, we conducted an open-label pharmacokinetics trial.