Development and Implementation of a Peer Curbside Consult Service for Pediatric Hospitalists.

Objective: To describe the development and implementation of a Peer Curbside Consult Service (PCCS) for a pediatric hospital medicine (PHM) division.

Methods: We developed a pilot intervention with hospitalists at a freestanding children's hospital to provide peer consultation services for challenging clinical cases. Postconsultation surveys collected from both the requesting and consulting hospitalists provided feedback about the program.

A quantitative analysis of MDMA seized at New South Wales music festivals over the 2019/2020 season: Form, purity, dose and adulterants.

Introduction: This research aims to understand the content and nature, and to explore the harm potential, of suspected 3,4-methylenedioxymethamphetamine (MDMA) substances circulating at music festivals in New South Wales.

Methods: Across 19 music festivals held between October 2019 and March 2020, 302 substances detected and suspected by police to contain MDMA were selected for quantitative analysis.

Results: Five percent of substances contained a drug other than MDMA (n = 13) or no drug (n = 2).

Rates of neonatal morbidity by maternal region of birth and gestational age in New South Wales, Australia 2003-2016.

Introduction: Research suggests that neonatal morbidity differs by maternal region of birth at different gestational ages. This study aimed to determine the overall and gestation-specific risk of neonatal morbidity by maternal region of birth, after adjustment for maternal, infant and birth characteristics, for women giving birth in New South Wales, Australia, from 2003 to 2016.

Material And Methods: The study utilized a retrospective cohort study design using linked births, hospital and deaths data.

P2X receptor knockout mice display less aggressive biting behaviour correlating with increased brain activation in the piriform cortex.

P2X receptors are implicated in the pathophysiology of psychiatric conditions such as depression and bipolar disorder. P2X receptors regulate the release of pro-inflammatory cytokines from microglia, and gain-of-function P2X mutations may contribute to the neuroinflammation found in affective disorders. However, the role of this receptor in mediating other mental health conditions and aberrant behaviours requires further examination.

CD8 lymphocytes but not B lymphocytes are required for protection against chronic hepatitis E virus infection in chickens.

Hepatitis E is an important global disease, causing outbreaks of acute hepatitis in many developing countries and sporadic cases in industrialized countries. Hepatitis E virus (HEV) infection typically causes self-limiting acute hepatitis but can also progress to chronic disease in immunocompromised individuals. The immune response necessary for the prevention of chronic infection is T cell-dependent; however, the arm of cellular immunity responsible for this protection is not currently known.

Microglial cell hyper-ramification and neuronal dendritic spine loss in the hippocampus and medial prefrontal cortex in a mouse model of PTSD.

Few animal models exist that successfully reproduce several core associative and non-associative behaviours relevant to post-traumatic stress disorder (PTSD), such as long-lasting fear reactions, hyperarousal, and subtle attentional and cognitive dysfunction. As such, these models may lack the face validity required to adequately model pathophysiological features of PTSD such as CNS grey matter loss and neuroinflammation. Here we aimed to investigate in a mouse model of PTSD whether contextual fear conditioning associated with a relatively high intensity footshock exposure induces loss of neuronal dendritic spines in various corticolimbic brain regions, as their regression may help explain grey matter reductions in PTSD patients.

Adrenocortical Challenge Response and Genomic Analyses in Scottish Terriers With Increased Alkaline Phosphate Activity.

Scottish terriers (ST) frequently have increased serum alkaline phosphatase (ALP) of the steroid isoform. Many of these also have high serum concentrations of adrenal sex steroids. The study's objective was to determine the cause of increased sex steroids in ST with increased ALP.

Nrg1 deficiency modulates the behavioural effects of prenatal stress in mice.

Little is known about the exact genes that confer vulnerability or resilience to environmental stressors during early neurodevelopment. Partial genetic deletion of neuregulin 1 (Nrg1) moderates the neurobehavioural effects of stressors applied in adolescence and adulthood, however, no study has yet examined its impact on prenatal stress. Here we examined whether Nrg1 deficiency in mice modulated the impact of prenatal stress on various behaviours in adulthood.

Genetic deletion of P-glycoprotein alters stress responsivity and increases depression-like behavior, social withdrawal and microglial activation in the hippocampus of female mice.

P-glycoprotein (P-gp) is an ABC transporter expressed at the blood brain barrier and regulates the brain uptake of various xenobiotics and endogenous mediators including glucocorticoid hormones which are critically important to the stress response. Moreover, P-gp is expressed on microglia, the brain's immune cells, which are activated by stressors and have an emerging role in psychiatric disorders. We therefore hypothesised that germline P-gp deletion in mice might alter the behavioral and microglial response to stressors.

Interactions between cannabidiol and Δ-THC following acute and repeated dosing: Rebound hyperactivity, sensorimotor gating and epigenetic and neuroadaptive changes in the mesolimbic pathway.

The evidence base for the use of medical cannabis preparations containing specific ratios of cannabidiol (CBD) and Δ-tetrahydrocannabinol (THC) is limited. While there is abundant data on acute interactions between CBD and THC, few studies have assessed the impact of their repeated co-administration. We previously reported that CBD inhibited or potentiated the acute effects of THC dependent on the measure being examined at a 1:1 CBD:THC dose ratio.

Intraventricular fibrinolysis with tissue plasminogen activator is associated with transient cerebrospinal fluid inflammation: a randomized controlled trial.

Locally administered tissue plasminogen activator (TPA) accelerates clearance of intraventricular hemorrhage (IVH), but its impact on neurologic outcomes remains unclear and preclinical research suggests it may have pro-inflammatory effects. We randomly allocated patients with ruptured cerebral aneurysms and IVH, treated with endovascular coiling and ventricular drainage, to receive either 2-mg intraventricular TPA or placebo every 12 hours. Cerebrospinal fluid (CSF) and serum cytokine and white blood cell (WBC) concentrations were measured before drug administration and daily for 72 hours.

Pharmacokinetics and Pharmacodynamics of Tissue Plasminogen Activator Administered Through an External Ventricular Drain.

Background: Intraventricular hemorrhage (IVH) frequently complicates spontaneous intracerebral or subarachnoid hemorrhage (SAH). Administration of intraventricular tissue plasminogen activator (TPA) accelerates blood clearance, but optimal dosing has not been clarified. Using a standardized TPA dose, we assessed peak cerebrospinal fluid (CSF) TPA concentrations, the rate at which TPA clears, and the relationship between TPA concentration and biological activity.

Partial genetic deletion of neuregulin 1 and adolescent stress interact to alter NMDA receptor binding in the medial prefrontal cortex.

Schizophrenia is thought to arise due to a complex interaction between genetic and environmental factors during early neurodevelopment. We have recently shown that partial genetic deletion of the schizophrenia susceptibility gene neuregulin 1 (Nrg1) and adolescent stress interact to disturb sensorimotor gating, neuroendocrine activity and dendritic morphology in mice. Both stress and Nrg1 may have converging effects upon N-methyl-D-aspartate receptors (NMDARs) which are implicated in the pathogenesis of schizophrenia, sensorimotor gating and dendritic spine plasticity.

Intraventricular tissue plasminogen activator in subarachnoid hemorrhage patients: a prospective, randomized, placebo-controlled pilot trial.

Background: The quantity of subarachnoid (SAH) and intraventricular hemorrhage (IVH) occurring in the setting of a ruptured cerebral aneurysm is strongly associated with subsequent complications and poor outcomes.

Methods: We randomly allocated aneurysmal SAH patients with a modified Fisher score of 4, who had been treated with endovascular coil embolization and ventricular drainage, to receive either 2 mg intraventricular tissue plasminogen activator (TPA) every 12 h (maximum 10 mg) or placebo. Computed tomography scans were performed 12, 48, and 72 h after administration.

Association between the cerebral inflammatory and matrix metalloproteinase responses after severe traumatic brain injury in humans.

An increasing number of preclinical investigations have suggested that the degree of expression of the matrix metalloproteinase (MMP) family of endopeptidases may explain some of the variability in neurological damage after traumatic brain injury (TBI). As cytokines are a prominent stimulus for MMP expression in animals, we conducted a prospective multimodal monitoring study and determined their association with temporal MMP expression after severe TBI in eight critically ill adults. High cutoff, cerebral microdialysis (n=8); external ventricular drainage (n=3); and arterial and jugular venous bulb catheters were used to measure the concentration of nine cytokines and eight MMPs in microdialysate, cerebrospinal fluid (CSF), and plasma over 6 days.

A prospective evaluation of the temporal matrix metalloproteinase response after severe traumatic brain injury in humans.

Abstract Accumulating pre-clinical data suggests that matrix metalloproteinase (MMP) expression plays a critical role in the pathophysiology of secondary brain injury. We conducted a prospective multimodal monitoring study in order to characterize the temporal MMP response after severe traumatic brain injury (TBI) in eight critically ill humans and its relationship with outcomes. High-cutoff, cerebral microdialysis (n=8); external ventricular drainage (n=3); and arterial and jugular venous bulb catheters were used to collect microdialysate, cerebrospinal fluid, and arterial and jugular bulb blood over 6 days.

Mortality associated with withdrawal of life-sustaining therapy for patients with severe traumatic brain injury: a Canadian multicentre cohort study.

Background: Severe traumatic brain injury often leads to death from withdrawal of life-sustaining therapy, although prognosis is difficult to determine.

Methods: To evaluate variation in mortality following the withdrawal of life-sustaining therapy and hospital mortality in patients with critical illness and severe traumatic brain injury, we conducted a two-year multicentre retrospective cohort study in six Canadian level-one trauma centres. The effect of centre on hospital mortality and withdrawal of life-sustaining therapy was evaluated using multivariable logistic regression adjusted for baseline patient-level covariates (sex, age, pupillary reactivity and score on the Glasgow coma scale).