Behaviour Concerns in Preschool Cardiac Surgery Survivors.

Background: Behaviour concerns (BC) are reported in survivors of complex cardiac surgery (CCSx) with inconsistent evidence about health and demographic variables that impact outcomes.

Methods: A prospective inception-cohort study of infants (without known chromosomal abnormalities) after CCSx from 2001 to 2017 determined Behaviour Assessment System for Children (BASC-II/III) parent rating scales at 4.5 years.

Are estimates of faces' ages less accurate when they wear sunglasses or face masks and do these disguises make it harder to later recognise the faces when undisguised?

This study examined whether our ability to accurately estimate unfamiliar faces' ages declines when they are wearing sunglasses or surgical-style face masks and whether these disguises make it harder to later recognise those faces when undisguised. In theory, both disguises should harm age estimation accuracy and later face recognition as they occlude facial information that is used to determine a face's age and identity. To establish whether this is the case, we had participants estimate the age of unfamiliar faces that were pictured wearing no disguises, sunglasses, or face masks.

Pre-school neurocognitive and functional outcomes after liver transplant in children with early onset urea cycle disorders, maple syrup urine disease, and propionic acidemia: An inception cohort matched-comparison study.

Background: Urea cycle disorders (UCD) and organic acid disorders classically present in the neonatal period. In those who survive, developmental delay is common with continued risk of regression. Liver transplantation improves the biochemical abnormality and patient survival is good.

Kindergarten-age neurocognitive, functional, and quality-of-life outcomes after liver transplantation at under 6 years of age.

Background: We aimed to describe school-entry age neurocognitive, functional, and HRQL outcomes and their predictors after liver transplant done at age <6 years.

Methods: A prospective cohort of all (n = 69) children surviving liver transplant from 1999 to 2014 were assessed at age 55.4 (SD 7.

Dosage Related Efficacy and Tolerability of Cannabidiol in Children With Treatment-Resistant Epileptic Encephalopathy: Preliminary Results of the CARE-E Study.

There is uncertainty regarding the appropriate dose of Cannabidiol (CBD) for childhood epilepsy. We present the preliminary data of seven participants from the Cannabidiol in Children with Refractory Epileptic Encephalopathy (CARE-E) study. The study is an open-label, prospective, dose-escalation trial.

Fluoromethylcyclopropylamine derivatives as potential in vivo toxicophores - A cautionary disclosure.

Fluorination of metabolic hotspots in a molecule is a common medicinal chemistry strategy to improve in vivo half-life and exposure and, generally, this strategy offers significant benefits. Here, we report the application of this strategy to a series of poly-ADP ribose glycohydrolase (PARG) inhibitors, resulting in unexpected in vivo toxicity which was attributed to this single-atom modification.

Neurocognitive and functional outcomes at 5 years of age after renal transplant in early childhood.

Background: Clinicians often use information about developmental outcomes in decision-making around offering complex, life-saving interventions in children such as dialysis and renal transplant. This information in children with end-stage renal disease (ESRD) is limited, particularly when ESRD onset is in infancy or early childhood.

Methods: Using data from an ongoing prospective, longitudinal, inception cohort study of children with renal transplant before 5 years of age, we evaluated (1) the risk of adverse neurocognitive and functional outcomes at 5 years of age and (2) predictors of developmental outcomes.

Cannabis for the treatment of paediatric epilepsy? An update for Canadian paediatricians.

The plant produces over 140 known cannabinoids. These chemicals generate considerable interest in the medical research community for their possible application to several intractable disease conditions. Recent reports have prompted parents to strongly consider Cannabis products to treat their children with drug resistant epilepsy.

Cell-Active Small Molecule Inhibitors of the DNA-Damage Repair Enzyme Poly(ADP-ribose) Glycohydrolase (PARG): Discovery and Optimization of Orally Bioavailable Quinazolinedione Sulfonamides.

DNA damage repair enzymes are promising targets in the development of new therapeutic agents for a wide range of cancers and potentially other diseases. The enzyme poly(ADP-ribose) glycohydrolase (PARG) plays a pivotal role in the regulation of DNA repair mechanisms; however, the lack of potent drug-like inhibitors for use in cellular and in vivo models has limited the investigation of its potential as a novel therapeutic target. Using the crystal structure of human PARG in complex with the weakly active and cytotoxic anthraquinone 8a, novel quinazolinedione sulfonamides PARG inhibitors have been identified by means of structure-based virtual screening and library design.

The protocol for the Cannabidiol in children with refractory epileptic encephalopathy (CARE-E) study: a phase 1 dosage escalation study.

Background: Initial studies suggest pharmaceutical grade cannabidiol (CBD) can reduce the frequency of convulsive seizures and lead to improvements in quality of life in children affected by epileptic encephalopathies. With limited access to pharmaceutical CBD, Cannabis extracts in oil are becoming increasingly available. Physicians show reluctance to recommend Cannabis extracts given the lack of high quality safety data especially regarding the potential for harm caused by other cannabinoids, such as Δ-tetrahydrocannabinol (Δ-THC).

Neurocognitive outcomes after heart transplantation in early childhood.

Background: Children requiring heart transplantation (HTx) for congenital heart disease (CHD) or failing anatomically normal hearts (CMP) face different challenges pre-HTx. We compared the neurocognitive capabilities in pre-school-age children receiving HTx for CHD vs CMP and determined factors predicting outcomes.

Methods: Data were collected within a prospective multi-provincial project from children who underwent HTx ≤4 years of age between 1999 and 2011.

Hypoplastic Left Heart Syndrome is not Associated with Worse Clinical or Neurodevelopmental Outcomes Than Other Cardiac Pathologies After the Norwood-Sano Operation.

There is evidence to suggest that patients undergoing a Norwood for non-HLHS anatomy may have lower mortality than classic HLHS, but differences in neurodevelopmental outcome have not been assessed. Our objective was to compare survival and neurodevelopmental outcome during the same surgical era in a large, well-described cohort. All subjects who underwent a Norwood-Sano operation between 2005 and 2014 were included.

Screening for language delay after life-saving therapies in term-born infants.

Background: Strong recommendations have been made for the periodic developmental surveillance, screening, and evaluation of children with CHD. This supports similar calls for all at-risk children in order to provide timely, structured early developmental intervention that may improve outcomes. The aim of this study was to determine the accuracy of screening for language delay after life-saving therapies using the parent-completed vocabulary screen of the language Development Survey, by comparing screening with the individually administered language scores of the Bayley Scales of Infant and Toddler Development, Third edition.

Sepsis After Cardiac Surgery Early in Infancy and Adverse 4.5-Year Neurocognitive Outcomes.

Background: We aimed to determine whether sepsis is associated with neurocognitive outcomes 4.5 years after congenital heart disease surgery in early infancy.

Methods And Results: A secondary analysis from a prospective inception cohort included all children having congenital heart disease surgery done at ≤6 weeks of age with cardiopulmonary bypass at the Western Canadian referral center from 1996 to 2009.

Megakaryoblastic leukemia-1 is required for the development of bleomycin-induced pulmonary fibrosis.

Background: Fibrosing disorders of the lung, such as idiopathic pulmonary fibrosis, are characterized by progressive extracellular matrix accumulation that is driven by myofibroblasts. The transcription factor megakaryoblastic leukemia-1 (MKL1) mediates myofibroblast differentiation in response to several profibrotic stimuli, but the role it plays in mediating pulmonary fibrosis has not been fully elucidated. In this study, we utilized mice that had a germline deletion of MKL1 (MKL1 (-,-)) to determine the role that MKL1 plays in the development of bleomycin-induced pulmonary fibrosis.

Myofibroblasts exhibit enhanced fibronectin assembly that is intrinsic to their contractile phenotype.

Myofibroblasts have increased expression of contractile proteins and display augmented contractility. It is not known if the augmented contractile gene expression characterizing the myofibroblast phenotype impacts its intrinsic ability to assemble fibronectin (FN) and extracellular matrix. In this study we investigated whether myofibroblasts displayed increased rates of FN fibril assembly when compared with their undifferentiated counterparts.

Kainate receptors coexist in a functional complex with KCC2 and regulate chloride homeostasis in hippocampal neurons.

KCC2 is the neuron-specific K+-Cl(-) cotransporter required for maintaining low intracellular Cl(-), which is essential for fast inhibitory synaptic transmission in the mature CNS. Despite the requirement of KCC2 for inhibitory synaptic transmission, understanding of the cellular mechanisms that regulate KCC2 expression and function is rudimentary. We examined KCC2 in its native protein complex in vivo to identify key KCC2-interacting partners that regulate KCC2 function.

Neurocognitive outcomes at kindergarten entry after liver transplantation at <3 yr of age.

This prospective inception cohort study determines kindergarten-entry neurocognitive abilities and explores their predictors following liver transplantation at age <3 yr. Of 52 children transplanted (1999-2008), 33 (89.2%) of 37 eligible survivors had psychological assessment at age 54.

Neto2 is a KCC2 interacting protein required for neuronal Cl- regulation in hippocampal neurons.

KCC2 is a neuron-specific K(+)-Cl(-) cotransporter that is essential for Cl(-) homeostasis and fast inhibitory synaptic transmission in the mature CNS. Despite the critical role of KCC2 in neurons, the mechanisms regulating its function are not understood. Here, we show that KCC2 is critically regulated by the single-pass transmembrane protein neuropilin and tolloid like-2 (Neto2).

Ceramide and its transport protein (CERT) contribute to deterioration of mitochondrial structure and function in aging oocytes.

In women as well as in mice, oocytes exhibit decreased developmental potential (oocyte quality) with advanced age. Our current data implicate alterations in the levels of oocyte ceramide and associated changes in mitochondrial function and structure as being prominent elements contributing to reduced oocyte quality. Both ROS levels and ATP content were significantly reduced in aged oocytes.

Hyperpolarizing GABAergic transmission requires the KCC2 C-terminal ISO domain.

KCC2 is the neuron-specific member of the of K(+)-Cl(-) cotransporter gene family. It is also the only member of its family that is active under physiologically normal conditions, in the absence of osmotic stress. By extruding Cl(-) from the neuron under isotonic conditions, this transporter maintains a low concentration of neuronal Cl(-), which is essential for fast inhibitory synaptic transmission by GABA and glycine in the mature nervous system.

NLRP5 mediates mitochondrial function in mouse oocytes and embryos.

Unraveling molecular pathways responsible for regulation of early embryonic development is crucial for our understanding of female infertility. Maternal determinants that control the transition from oocyte to embryo are crucial molecules that govern developmental competence of the newly conceived zygote. We describe a series of defects that are triggered by a disruption of maternal lethal effect gene, Nlrp5.

Overestimating neurodevelopment using the Bayley-III after early complex cardiac surgery.

Background: The newest measure of neurodevelopmental outcomes, the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III), gives higher-than-expected scores for preterm infants; results after cardiac surgery are unknown.

Objectives: The goal of this study was to report Bayley-III scores after cardiac surgery and compare the results with those of the Bayley Scales of Infant Development, 2nd Edition (BSID-II) on a subset of the same children.

Methods: In this prospective, inception cohort, neurodevelopmental outcome study after complex cardiac surgery in infants from 2004 to 2007, the Bayley-III was given to 110 survivors (68% boys) at a mean age of 21 months (SD: 4 months).

Outcomes after heart transplantation in children under six years of age.

Background: Survival after heart transplant has improved and more attention is focused on developmental outcomes. We aimed to determine the survival, morbidity, and developmental outcomes of young children after heart transplant.

Methods: All children under 6 years of age having a heart transplant in Edmonton between 1999 and 2006 were included in this inception cohort study.