Measuring the immunogenicity of pneumococcal vaccines involves the use of immunoassays to measure serotype-specific immunoglobulin G (IgG) antibody levels post-vaccination with the current human reference serum standard (007sp) for anti-pneumococcal capsule antibodies. Development of new pneumococcal conjugate vaccines (PCVs) with additional serotypes not in 007sp (e.g.
View Article and Find Full Text PDFImportance: Neonates requiring surgery are often cared for in neonatal intensive care units (NICUs). Despite a breadth of surgical pathology, neonates share many perioperative priorities that allow for the development of unit-wide evidence-based Enhanced Recovery After Surgery (ERAS) recommendations.
Observations: The guideline development committee included pediatric surgeons, anesthesiologists, neonatal nurses, and neonatologists in addition to ERAS content and methodology experts.
Introduction: Enhanced Recovery After Surgery (ERAS®) protocols require multidisciplinary team engagement from healthcare professionals (HCPs), where limited studies exist on neonatal ERAS®protocols. Therefore, we aimed to capture perceptions of HCPs on facilitation and implementation of the neonatal ERAS®guideline.
Methods: 10 neonates were recruited.
Introduction: Enhanced Recovery After Surgery (ERAS) guidelines are bundled evidence-informed recommendations implemented to improve quality and safety of perioperative care. This study aims to determine feasibility of NICU implementation of an ERAS Guideline for Intestinal Resection, describing clinical outcomes and adherence to recommendations following light-touch implementation.
Methods: Infants <28 days undergoing laparotomy for intestinal resection in a closed-NICU were prospectively enrolled.
Background: Parents endure significant stress when their newborns require surgery while in the neonatal intensive care unit (NICU). Our study aims to explore the surgical NICU experience from the parents' perspective and identify areas that may improve this experience. A secondary objective was to integrate their feedback to refine the implementation strategy of the neonatal enhanced recovery after surgery (ERAS) guideline.
View Article and Find Full Text PDFThe cannabis derivative marijuana is the most widely used recreational drug in the Western world and is consumed by an estimated 83 million individuals (∼3% of the world population). In recent years, there has been a marked transformation in society regarding the risk perception of cannabis, driven by its legalization and medical use in many states in the United States and worldwide. Compelling research evidence and the Food and Drug Administration cannabis-derived cannabidiol approval for severe childhood epilepsy have confirmed the large therapeutic potential of cannabidiol itself, Δ-tetrahydrocannabinol and other plant-derived cannabinoids (phytocannabinoids).
View Article and Find Full Text PDFAlthough use of is not associated with serious adverse effects, recreational use of aminoalkylindole (AAI) cannabinoid receptor agonists found in K2/Spice herbal blends has been reported to cause adverse cardiovascular events, including angina, arrhythmia, changes in blood pressure, ischemic stroke, and myocardial infarction. Δ-Tetrahydrocannabinol (Δ-THC) is the primary CB agonist found in cannabis and JWH-073 is one of the AAI CB agonists found in K2/Spice brands sold to the public. This study used , , and approaches to investigate potential differences on cardiac tissue and vascular effects betweenJWH-073 and Δ-THC.
View Article and Find Full Text PDFTher Hypothermia Temp Manag
September 2023
Hypoxic-ischemic encephalopathy (HIE) and associated multiorgan injury are significant causes of morbidity and mortality in term and near-term neonates. Therapeutic hypothermia (TH) is the current standard of care for neuroprotection in neonates with HIE. In our experience, the majority of babies born with HIE were found in nontertiary care facilities in our region, where effective methods of cooling during transport to tertiary care centers are desirable.
View Article and Find Full Text PDFStudy Objective: To describe the impact of protocol-driven dexmedetomidine (and clonidine) use on opioid exposure in post-surgical neonates.
Design: Retrospective chart review.
Setting: A Level III, surgical NICU.
The alkylindole (AI), WIN55212-2, modulates the activity of several proteins, including cannabinoid receptors 1 and 2 (CBR, CBR), and at least additional G protein-coupled receptor (GPCR) that remains uncharacterized with respect to its molecular identity and pharmacological profile. Evidence suggests that such AI-sensitive GPCRs are expressed by the human kidney cell line HEK293. We synthesized fourteen novel AI analogues and evaluated their activities at AI-sensitive GPCRs using [S]GTPγS and [H]WIN55212-2 binding in HEK293 cell membranes, and performed in silico pharmacophore modeling to identify characteristics that favor binding to AI-sensitive GPCRs versus CBR/CBR.
View Article and Find Full Text PDFBackground: Trainees aiming to specialize in Neonatal Perinatal Medicine (NPM), must be competent in a wide range of procedural skills as per the Royal College of Canada. While common neonatal procedures are frequent in daily clinical practice with opportunity to acquire competence, there are substantial gaps in the acquisition of advanced neonatal procedural skills. With the advent of competency by design into NPM training, simulation offers a unique opportunity to acquire, practice and teach potentially life-saving procedural skills.
View Article and Find Full Text PDFThe function of the dopamine transporter (DAT) is regulated by membrane cholesterol content. A direct, acute removal of membrane cholesterol by methyl-β-cyclodextrin (MβCD) has been shown to reduce dopamine (DA) uptake and release mediated by the DAT. This is of particular interest because a few widely prescribed statins that lower peripheral cholesterol levels are blood-brain barrier (BBB) penetrants, and therefore could alter DAT function through brain cholesterol modulation.
View Article and Find Full Text PDFThe CB cannabinoid receptor (CBR) and extracellular calcium (eCa)-stimulated Calcium Sensing receptor (CaSR) can exert cellular signaling by modulating levels of intracellular calcium ([Ca]). We investigated the mechanisms involved in the ([Ca]) increase in N18TG2 neuroblastoma cells, which endogenously express both receptors. Changes in [Ca] were measured in cells exposed to 0.
View Article and Find Full Text PDFObjective: To determine the relationship between number of attempts and adverse events during neonatal intubation.
Study Design: A retrospective study of prospectively collected data of intubations in the delivery room and NICU from the National Emergency Airway Registry for Neonates (NEAR4NEOS) in 17 academic centers from 1/2016 to 12/2019. We examined the association between tracheal intubation attempts [1, 2, and ≥3 (multiple attempts)] and clinical adverse outcomes (any tracheal intubation associated events (TIAE), severe TIAE, and severe oxygen desaturation).
To enable benchmarking of immunogenicity between candidate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, there is a need for standardized, validated immunogenicity assays. In this article, we report the design and criteria used to validate immunogenicity assays and the outcome of the validation of serologic and functional assays for the evaluation of functional immune response and antibody titers in human serum. A quantitative cell-based microneutralization (MNT) assay, utilizing a reference standard, for detecting anti-SARS-CoV-2 spike protein-neutralizing antibodies in human serum and Meso Scale Discovery's multiplex electrochemiluminescence (MSD ECL) assay for immunoglobulin G (IgG) antibodies to SARS-CoV-2 spike, nucleocapsid, and receptor-binding domain (RBD) proteins were assessed for precision, accuracy, dilutional linearity, selectivity, and specificity using pooled human serum from coronavirus disease 2019 (COVID-19)-confirmed recovered donors.
View Article and Find Full Text PDFThe prevalence of the coronavirus SARS-CoV-2 disease has resulted in the unprecedented collection of health data to support research. Historically, coordinating the collation of such datasets on a national scale has been challenging to execute for several reasons, including issues with data privacy, the lack of data reporting standards, interoperable technologies, and distribution methods. The coronavirus SARS-CoV-2 disease pandemic has highlighted the importance of collaboration between government bodies, healthcare institutions, academic researchers and commercial companies in overcoming these issues during times of urgency.
View Article and Find Full Text PDFThe Sterling Research Group identified pravadoline as an aminoalkylindole (AAI) non-steroidal anti-inflammatory pain reliever. As drug design progressed, the ability of AAI analogs to block prostaglandin synthesis diminished, and antinociceptive activity was found to result from action at the CB cannabinoid receptor, a G-protein-coupled receptor (GPCR) abundant in the brain. Several laboratories applied computational chemistry methods to ultimately conclude that AAI and cannabinoid ligands could overlap within a common binding pocket but that WIN55212-2 primarily utilized steric interactions via aromatic stacking, whereas cannabinoid ligands required some electrostatic interactions, particularly involving the CB helix-3 lysine.
View Article and Find Full Text PDFCannabinoid receptor interacting protein 1a (CRIP1a) modulates CB cannabinoid receptor G-protein coupling in part by altering the selectivity for Gα subtype activation, but the molecular basis for this function of CRIP1a is not known. We report herein the first structure of CRIP1a at a resolution of 1.55 Å.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
February 2022
The endocannabinoid system (ECS) is a cell-signaling system present in multiple organ systems and is an integral part of sustaining the microenvironment necessary for early pregnancy success and maintenance. It plays a significant role in embryo development, transport and implantation as well as placentation. The current theory behind the initiation of term labor is that it is a complex, multifactorial process involving sex steroid hormones, prostaglandin production and interplay at the maternal-fetal interface resulting in increased expression of receptors and gap junctions that promote uterine activation.
View Article and Find Full Text PDFObjectives: To characterize neonatal-perinatal medicine fellows' progression toward neonatal intubation procedural competence during fellowship training.
Methods: Multi-center cohort study of neonatal intubation encounters performed by neonatal-perinatal medicine fellows between 2014 through 2018 at North American academic centers in the National Emergency Airway Registry for Neonates. Cumulative sum analysis was used to characterize progression of individual fellows' intubation competence, defined by an 80% overall success rate within 2 intubation attempts.
Introduction: Neonatal tracheal intubation (TI) outcomes have been assessed by role, but training level may impact TI success and safety. Effect of physician training level (PTL) on the first-attempt success, adverse TI-associated events (TIAEs), and oxygen desaturation was assessed.
Methods: Prospective cohort study in 11 international NEAR4NEOS sites between October 2014 and December 2017.
The endocannabinoid system is present in multiple organ systems and is involved in smooth muscle regulation, immune function, neuroendocrine modulation, and metabolism of tissues. Limited data are available regarding the presence and role of this system in reproductive tissues. Components of the endocannabinoid system have been identified in myometrial and placental tissues.
View Article and Find Full Text PDFBackground: Strong implementation strategies are critical to the success of Enhanced Recovery after Surgery (ERAS®) guidelines, though little documentation exists on effective strategies, especially in complex clinical situations and unfamiliar contexts. This study outlines the process taken to adopt a novel neonatal ERAS® guideline.
Methods: The implementation strategy was approached in a multi-pronged, concurrent but asynchronous fashion.
Phenmetrazine (PHEN) is a putative treatment for cocaine and psychostimulant recidivism; however, neurochemical changes underlying its activity have not been fully elucidated. We sought to characterize brain homeostatic adaptations to chronic PHEN, specifically on functional brain activity (local cerebral glucose utilization), G-Protein Coupled Receptor-stimulated G-protein activation, and phosphorylation of ERK1/2, GSK3β, and DARPP-32. Male Sprague-Dawley rats were implanted with sub-cutaneous minipumps delivering either saline (vehicle), acute (2-day) or chronic (14-day) low dose (25 mg/kg/day) or high dose (50 mg/kg/day) PHEN.
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