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So long, COVID!

As if the poor lab mouse hasn’t had it hard enough, these stoic cheese stealers are now encouraged to develop murine long-COVID. Brain fog is a common symptom and interleukin-1, critical in the innate defence against the pandemic virus, is elevated in the hippocampi of people who’ve had COVID. Researchers set out to investigate the impact of vaccination on this process. They confirm that SARS-CoV-2 but not H1N1 flu induces the indicative rise of interleukin-1beta and a persistent interleukin driven loss of hippocampal neurogenesis, which was ameliorated when the mice were vaccinated against COVID.

Nat Immunol. 2024 doi:10.1038/s41590-024-01868-z.

Any place-bo, any time

Neurological pragmatists keen to super-charge the placebo value of their prescriptions take note, it may matter as much what you prescribe for, than what you proffer. A systematic review of high-quality randomised controlled trials of psychiatric disorders identified 90 studies for inclusion (9985 participants). The placebo response was not uniform and they identify a spectrum from most likely to respond to the powerful sugar pill (major depressive disorder, generalised anxiety disorder) to least likely (schizophrenia, obsessive compulsive disorder). There was symptom improvement across all disorders studied, many of a considerable magnitude, and studies with the greatest proportion of women showed the greater placebo response.

JAMA Psychiatry. 2024 doi:10.1001/jamapsychiatry.2024.0994.

Genome sweet genome

How best to investigate for rare genetic disorders is till up for debate. When a rare monogenic disorder is suspected, what is the additional value for whole genome sequencing (WGS) when standard genetic testing has drawn a blank? 744 families were WGS sequenced, and 218 (29%) were subsequently diagnosed, 61 of whom (8% of the total) with disorders that could only have been identified via genome sequencing. On reflection 64% of the newly diagnosed cases could have been answered by re-scrutinising the existing genetic data. A smaller replication cohort, 78 families, confirmed these findings. Is it time to pick up that family with a SWAN (syndrome without a name) and wonder whether it may now be time to re-test?

N Engl J Med. 2024;390 (21):1985–1997.

Primum omnium cerebrum

A comprehensive theory has been published of how the brain modulates peripheral inflammatory response. The team demonstrated how both pro and anti-inflammatory cytokines communicate with specific vagal neurons as an ‘advance warning signal’ of an emergent inflammatory response, in mice. Silencing this circuit produced unregulated ‘wildfire’ immune responses. Showing that this axis is modifiable, provides insights into disease as disparate as diabetes and neurodegeneration, and opportunities for therapy. Specifically, the authors speculate that autoimmune disorders, toxic shock syndrome and hyperactive immune states provoked by new immunotherapies have the most to gain from this breakthrough. Within 6 months will we discover that the brain is the cause of all illness from athlete’s foot to indolent neurologist’s elbow?

Nature. 2024;630 (8017):695–703.

What would you do with a third thumb? Cambridge University researchers have now studied this on 596 participants and the video accompanying the recently published study (figure 1) is highly recommended. Sci Robot. 2024;9 (90):eadk5183.

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Footnotes

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; internally peer reviewed.