Increasing evidence suggests that SARS-CoV-2, the virus responsible for the COVID-19 pandemic, is associated with increased risk of developing neurological or psychiatric conditions such as depression, anxiety or dementia. While the precise mechanism underlying this association is unknown, aberrant activation of toll-like receptor (TLR)3, a viral recognizing pattern recognition receptor, may play a key role. Synthetic cannabinoids and enhancing cannabinoid tone via inhibition of fatty acid amide hydrolase (FAAH) has been demonstrated to modulate TLR3-induced neuroimmune responses and associated sickness behaviour. However, the role of individual FAAH substrates, and the receptor mechanisms mediating these effects, are unknown. The present study examined the effects of intracerebral or systemic administration of the FAAH substrates
N
-oleoylethanolamide (OEA),
N
-palmitoylethanolamide (PEA) or the anandamide (AEA) analogue meth-AEA on hyperthermia and hypothalamic inflammatory gene expression following administration of the TLR3 agonist, and viral mimetic, poly I:C. The data demonstrate that meth-AEA does not alter TLR3-induced hyperthermia or hypothalamic inflammatory gene expression. In comparison, OEA and PEA attenuated the TLR3-induced hyperthermia, although only OEA attenuated the expression of hyperthermia-related genes (
IL-1β, iNOS, COX2
and
m-PGES
) in the hypothalamus. OEA, but not PEA, attenuated TLR3-induced increases in the expression of all IRF- and NFκB-related genes examined in the hypothalamus, but not in the spleen. Antagonism of PPARα prevented the OEA-induced attenuation of IRF- and NFκB-related genes in the hypothalamus following TLR3 activation but did not significantly alter temperature. PPARα agonism did not alter TLR3-induced hyperthermia or hypothalamic inflammatory gene expression. These data indicate that OEA may be the primary FAAH substrate that modulates TLR3-induced neuroinflammation and hyperthermia, effects partially mediated by PPARα.
A single abdominal radiograph is insufficiently sensitive to rule out abdominal drug carriage. However, specificivity is high and a positive finding is diagnostic. Cochrane: 'heliox'
Search outcomeAltogether 207 papers were found, of which six were considered to be original research of high quality (randomised controlled trials) suitable for inclusion. Secondary citations from these papers were also scanned. These six papers have since been subject to meta-analysis by the Cochrane Review Group. The review was first published in 2000 with the most recent substantive amendment made in November 2002 (see table 2).
Comment(s)The individual trials examined in the Cochrane review vary widely in the type of patients recruited (age, severity of asthma), delivery of heliox and outcome measures. Outcomes vary between heliox having a beneficial effect and having no effect. There are very few side effects of heliox reported.c CLINICAL BOTTOM LINE At the moment the evidence does not support the use of heliox in the emergency department treatment of acute asthma exacerbations. Abstract A short cut review was carried out to establish whether cardiopulmonary bypass improves survival and function after cardiac arrest resistant to ACLS. Altogether 387 papers were found using the reported search, of which nine presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.
Clinical scenarioYou are the arrest team leader for a 56 year old patient that has just been brought in by emergency ambulance. He collapsed suddenly in the town centre, but had early, effective bystander CPR. Fourteen minutes have elapsed since and he remains in VF despite three prehospital DC
SUMMARYTwo cases of adult intussusception (large bowel and small bowel) are presented highlighting the challenges posed by their often innocuous presentation in addition to significant morbidity resulting from delayed diagnosis.
BACKGROUND
These findings call into question current practice. Clearly, multiple confounders exist in the context of process variability in a heterogeneous population such as that attending an emergency department. This study offer solutions to address this problem.
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