Using behavioural science to improve antibiotic stewardship in Canadian long-term care homes: Protocol for a multi-center cluster randomized quality improvement study.

Background: Antimicrobial resistance (AMR) is associated with significant human and financial costs, particularly among vulnerable populations like older adults living in long-term care homes (LTCHs). Urinary tract infection (UTI) is the leading indication for antibiotic use in this population, with some estimates suggesting that up to 70% of these prescriptions may be avoidable.

Objective: The purpose of this study is to develop and test novel behavioural science-informed antimicrobial stewardship (AMS) quality improvement strategies in Canadian LTCHs, which aim to decrease unnecessary testing and treatment for residents who lack the minimum clinical signs and symptoms of UTI.

Confidence and barriers: Analysis of factors associated with timely routine childhood vaccination in Canada during the COVID-19 pandemic.

Routine childhood vaccination is a crucial component of public health in Canada and worldwide. To facilitate catch-up from the global decline in routine vaccination caused by the COVID-19 pandemic, and toward the ongoing pursuit of coverage goals, vaccination programs must understand barriers to vaccine access imposed or exacerbated by the pandemic. We conducted a regionally representative online survey in January 2023 including 2036 Canadian parents with children under the age of 18.

Carnitine supplementation increases serum concentrations of free carnitine and total acylcarnitine in preterm neonates: A retrospective cohort study.

Objective: Our goal was to determine the efficacy of the American Society for Parenteral and Enteral Nutrition's recommended carnitine dosage of 5 mg/kg/day in maintaining normal serum free carnitine and total acylcarnitine levels in preterm neonates receiving parenteral nutrition (PN).

Study Design: A retrospective cohort study was conducted on neonates born <30 weeks gestation and weighing <1250 g, comparing those who received carnitine supplementation to those without supplementation. Free carnitine and total acylcarnitine data were collected from routine newborn screens in the first days of life and on full enetral feeds.

Antibiotic prescribing and antimicrobial stewardship in long-term care facilities: Past interventions and implementation challenges.

Background: The threat of antimicrobial resistance (AMR) is rising, leading to increased illness, death and healthcare costs. In long-term care facilities (LTCFs), high rates of infection coupled with high antibiotic use create a selective pressure for antimicrobial-resistant organisms that pose a risk to residents and staff as well as surrounding hospitals and communities. Antimicrobial stewardship (AMS) is paramount in the fight against AMR, but its adoption in LTCFs has been limited.

Method modification to reduce false positives for newborn screening of guanidinoacetate methyltransferase deficiency.

Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive disorder that results in reduced activity of guanidinoacetate methyltransferase, an accumulation of guanidinoacetate (GUAC), and a lack of cerebral creatine (CRE). Lack of CRE in the brain can cause intellectual disability, autistic-like behavior, seizures, and movement disorders. Identification at birth and immediate therapy can prevent intellectual disability and seizures.

Probing the functional consequence and clinical relevance of CD320 p.E88del, a variant in the transcobalamin receptor gene.

The biological and clinical significance of the p.E88del variant in the transcobalamin receptor, CD320, is unknown. This allele is annotated in ClinVar as likely benign, pathogenic, and of uncertain significance.

Prospective identification by neonatal screening of patients with guanidinoacetate methyltransferase deficiency.

Introduction: Guanidinoacetate methyltransferase (GAMT) deficiency is an inherited metabolic disorder that impairs the synthesis of creatine (CRE). Lack of CRE in the brain can cause intellectual disability, autistic-like behavior, seizures, and movement disorders. Identification at birth and immediate therapy can prevent intellectual disability and seizures.

Harmonizing Newborn Screening Laboratory Proficiency Test Results Using the CDC NSQAP Reference Materials.

Newborn screening (NBS) laboratories cannot accurately compare mass spectrometry-derived results and cutoff values due to differences in testing methodologies. The objective of this study was to assess harmonization of laboratory proficiency test (PT) results using quality control (QC) data. Newborn Screening Quality Assurance Program (NSQAP) QC and PT data reported from 302 laboratories in 2019 were used to compare results among laboratories.

Prefrontal Neural Ensembles Develop Selective Code for Stimulus Associations within Minutes of Novel Experiences.

Prevailing theories posit that the hippocampus rapidly learns stimulus conjunctions during novel experiences, whereas the neocortex learns slowly through subsequent, off-line interaction with the hippocampus. Parallel evidence, however, shows that the medial prefrontal cortex (mPFC; a critical node of the neocortical network supporting long-term memory storage) undergoes rapid modifications of gene expression, synaptic structure, and physiology at the time of encoding. These observations, along with impaired learning with disrupted mPFC, suggest that mPFC neurons may exhibit rapid neural plasticity during novel experiences; however, direct empirical evidence is lacking.

Distributed representations of temporal stimulus associations across regular-firing and fast-spiking neurons in rat medial prefrontal cortex.

The prefrontal cortex has been implicated in various cognitive processes, including working memory, executive control, decision making, and relational learning. One core computational requirement underlying all these processes is the integration of information across time. When rodents and rabbits associate two temporally discontiguous stimuli, some neurons in the medial prefrontal cortex (mPFC) change firing rates in response to the preceding stimulus and sustain the firing rate during the subsequent temporal interval.

Use of serum citrulline concentrations from routine newborn screen as a biomarker for necrotizing enterocolitis.

Purpose: Necrotizing enterocolitis (NEC), a leading cause of mortality and morbidity in preterm neonates, lacks a reliable biomarker. Citrulline is primarily produced by enterocytes and correlates with intestinal function. Serum citrulline concentration (CIT) is routinely measured in routine newborn screening (NBS).

Liquid chromatography-tandem mass spectrometry analysis of 17-hydroxyprogesterone in dried blood spots revealed matrix effect on immunoassay.

Immunoassays for measuring 17-hydroxyprogesterone (17-OHP) produce high rates of false positives that impact the identification of congenital adrenal hyperplasia (CAH) in neonates. A confirmatory test with high analytical specificity employing liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology is needed in newborn screening for CAH. 17-OHP and cortisol were extracted from dried blood spot (DBS) samples, resolved on a C18 column, and measured using tandem mass spectrometry.

The role of engram cells in the systems consolidation of memory.

What happens to memories as days, weeks and years go by has long been a fundamental question in neuroscience and psychology. For decades, researchers have attempted to identify the brain regions in which memory is formed and to follow its changes across time. The theory of systems consolidation of memory (SCM) suggests that changes in circuitry and brain networks are required for the maintenance of a memory with time.

Comparison of C26:0-carnitine and C26:0-lysophosphatidylcholine as diagnostic markers in dried blood spots from newborns and patients with adrenoleukodystrophy.

X-linked adrenoleukodystrophy (ALD) is the most common leukodystrophy with a birth incidence of 1:14,700 live births. The disease is caused by mutations in ABCD1 and characterized by very long-chain fatty acids (VLCFA) accumulation. In childhood, male patients are at high-risk to develop adrenal insufficiency and/or cerebral demyelination.

Neonatal detection of Aicardi Goutières Syndrome by increased C26:0 lysophosphatidylcholine and interferon signature on newborn screening blood spots.

Background: Aicardi Goutières Syndrome (AGS) is a heritable interferonopathy associated with systemic autoinflammation causing interferon (IFN) elevation, central nervous system calcifications, leukodystrophy and severe neurologic sequelae. An infant with TREX1 mutations was recently found to have abnormal C26:0 lysophosphatidylcholine (C26:0 Lyso-PC) in a newborn screening platform for X-linked adrenoleukodystrophy, prompting analysis of this analyte in retrospectively collected samples from individuals affected by AGS.

Methods: In this study, we explored C26:0 Lyso-PC levels and IFN signatures in newborn blood spots and post-natal blood samples in 19 children with a molecular and clinical diagnosis of AGS and in the blood spots of 22 healthy newborns.

Entorhinal tau pathology disrupts hippocampal-prefrontal oscillatory coupling during associative learning.

A neural signature of asymptomatic preclinical Alzheimer's disease (AD) is disrupted connectivity between brain regions; however, its underlying mechanisms remain unknown. Here, we tested whether a preclinical pathologic feature, tau aggregation in the entorhinal cortex (EC) is sufficient to disrupt the coordination of local field potentials (LFPs) between its efferent regions. P301L-mutant human tau or green fluorescent protein (GFP) was virally overexpressed in the EC of adult rats.

Phasic and tonic neuron ensemble codes for stimulus-environment conjunctions in the lateral entorhinal cortex.

The lateral entorhinal cortex (LEC) is thought to bind sensory events with the environment where they took place. To compare the relative influence of transient events and temporally stable environmental stimuli on the firing of LEC cells, we recorded neuron spiking patterns in the region during blocks of a trace eyeblink conditioning paradigm performed in two environments and with different conditioning stimuli. Firing rates of some neurons were phasically selective for conditioned stimuli in a way that depended on which room the rat was in; nearly all neurons were tonically selective for environments in a way that depended on which stimuli had been presented in those environments.

Engrams and circuits crucial for systems consolidation of a memory.

Episodic memories initially require rapid synaptic plasticity within the hippocampus for their formation and are gradually consolidated in neocortical networks for permanent storage. However, the engrams and circuits that support neocortical memory consolidation have thus far been unknown. We found that neocortical prefrontal memory engram cells, which are critical for remote contextual fear memory, were rapidly generated during initial learning through inputs from both the hippocampal-entorhinal cortex network and the basolateral amygdala.

Generalizable knowledge outweighs incidental details in prefrontal ensemble code over time.

Memories for recent experiences are rich in incidental detail, but with time the brain is thought to extract latent rules and structures common across past experiences. We show that over weeks following the acquisition of two distinct associative memories, neuron firing in the rat prelimbic prefrontal cortex (mPFC) became less selective for perceptual features unique to each association and, with an apparently different time-course, became more selective for common relational features. We further found that during exposure to a novel experimental context, memory expression and neuron selectivity for relational features immediately generalized to the new situation.

Cholinergic, but not NMDA, receptors in the lateral entorhinal cortex mediate acquisition in trace eyeblink conditioning.

Anatomical and electrophysiological studies collectively suggest that the entorhinal cortex consists of several subregions, each of which is involved in the processing of different types of information. Consistent with this idea, we previously reported that the dorsolateral portion of the entorhinal cortex (DLE), but not the caudomedial portion, is necessary for the expression of a memory association between temporally discontiguous stimuli in trace eyeblink conditioning (Morrissey et al. (2012) J Neurosci 32:5356-5361).

Parvalbumin and GAD65 interneuron inhibition in the ventral hippocampus induces distinct behavioral deficits relevant to schizophrenia.

Hyperactivity within the ventral hippocampus (vHPC) has been linked to both psychosis in humans and behavioral deficits in animal models of schizophrenia. A local decrease in GABA-mediated inhibition, particularly involving parvalbumin (PV)-expressing GABA neurons, has been proposed as a key mechanism underlying this hyperactive state. However, direct evidence is lacking for a causal role of vHPC GABA neurons in behaviors associated with schizophrenia.

Diversity of mnemonic function within the entorhinal cortex: a meta-analysis of rodent behavioral studies.

The entorhinal cortex (EC) has been shown to be an integral piece of the hippocampal memory system. It sits in a unique position within the brain with strong, intricate, reciprocal connectivity with the hippocampus as well as a vast array of neocortical regions. Topographical patterns of afferent and efferent projections suggest that the EC can be divided into the medial and lateral regions, each of which can be further divided into dorsal, intermediate, and lateral bands.

Unilateral lateral entorhinal inactivation impairs memory expression in trace eyeblink conditioning.

Memory in trace eyeblink conditioning is mediated by an inter-connected network that involves the hippocampus (HPC), several neocortical regions, and the cerebellum. This network reorganizes after learning as the center of the network shifts from the HPC to the medial prefrontal cortex (mPFC). Despite the network reorganization, the lateral entorhinal cortex (LEC) plays a stable role in expressing recently acquired HPC-dependent memory as well as remotely acquired mPFC-dependent memory.