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Does anyone have the reference to the "researchers should be spending more time on literature reviews" study? 2021-09-26T21:47:16.732Z

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Comment by tb_throwaway on Theses on Sleep · 2022-02-14T21:23:34.955Z · LW · GW

There's a lot of interesting stuff in the post, but the following counter-point you offer to "the idea that sleep’s purpose is metabolite clearance" I can't quite follow:

The paper is called “Sleep Drives Metabolite Clearance from the Adult Brain”. The abstract says:

The conservation of sleep across all animal species suggests that sleep serves a vital function. We here report that sleep has a critical function in ensuring metabolic homeostasis. Using real-time assessments of tetramethylammonium diffusion and two-photon imaging in live mice, we show that natural sleep or anesthesia are associated with a 60% increase in the interstitial space, resulting in a striking increase in convective exchange of cerebrospinal fluid with interstitial fluid. In turn, convective fluxes of interstitial fluid increased the rate of β-amyloid clearance during sleep. Thus, the restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.

At the same time, the paper found that anesthesia without sleep results in the same clearance (paper: “Aβ clearance did not differ between sleeping and anesthetized mice”), meaning that clearance is not caused by sleep per se, but instead only co-occurrs with it. Authors did not mention this in the abstract and mistitled the paper, thus misleading the readers. As far as I can tell, literally nobody pointed this out previously.

I'm not quite following the meaning that clearance is not caused by sleep per se, but instead only co-occurrs with it bit. So yes, sleep allegedly results in X (clearance), that you can also get through, e.g., anesthesia. I don't see how this is more misleading than a statement like exercise results in autophagy which you can also get by using exercise mimetics hypothetically would be (if/when we had enough data on exercise mimetics, for ex.). Basically, you can get to a good thing (clearance/autophagy) in both of these cases through various means. Why would this be a misleading thing to say about sleep/exercise?

 

Is the idea that we should be seeking to anesthetize ourselves (without sleep) to get these specific benefits at least, instead of committing to more sleep (which would be an overkill in this presentation)?

 

Not responding to the broader reaction to this paper in your post btw, just this one bit. Thanks

 

EDIT: I also want to note that you don't seem to address the role of sleep in immune function/lowering systemic inflammation markers beyond Walker's failures of citations. There's a bunch of literature on this on pubmed etc., which tbf I haven't reviewed in detail so perhaps it's all bunk! But it would've been good to have insight into that, as my impression ATM is that sleep certainly strengthens your immune system and lowers systemic inflammation.

Comment by tb_throwaway on Coronavirus: Justified Practical Advice Thread · 2020-03-30T20:08:25.404Z · LW · GW

@leggi, thanks, I think the key thing here is that BCG isn't used to protect you against TB here, but broadly boost your immune system. I found a bunch of papers on this (admittedly, many about youth, but also some on the elderly getting BCG):


https://www.ncbi.nlm.nih.gov/pubmed/25725054
https://www.ncbi.nlm.nih.gov/pubmed/21979284
https://www.ncbi.nlm.nih.gov/pubmed/27737834
https://www.sciencedirect.com/science/article/pii/S1931312817305462?via%3Dihub
https://science.sciencemag.org/content/352/6284/aaf1098
https://www.bmj.com/content/355/bmj.i5170
https://www.who.int/immunization/sage/meetings/2014/april/3_NSE_Epidemiology_review_Report_to_SAGE_14_Mar_FINAL.pdf
https://www.bandim.org/-/media/arkiv/projekt-sites/bandim/pdf/bhp-vaccines.pdf?la=en
https://www.clinicaltherapeutics.com/article/S0149-2918(13)00014-3/pdf
https://www.mpg.de/14491738/0219-mpin-116799-modified-tuberculosis-vaccine-as-a-therapy-for-cancer-of-the-bladder


What I want to call out in the context of the elderly:

https://www.ncbi.nlm.nih.gov/pubmed/21979284

The efficacy of Bacillus Calmette-Guerin vaccinations for the prevention of acute upper respiratory tract infection in the elderly.
AIM: to study the efficacy of BCG vaccinations, once a month for 3 consecutive months, in elderly on the prevention of acute upper respiratory tract infection (AURTI), interferon - gamma (IFN-γ) and interleukin (IL)-10 level in the BCG and placebo group and their comparison in the period of the study.
CONCLUSION: BCG vaccinations in elderly, once a month for 3 consecutive months, significantly prevent the AURTI and can increase the IFN-γ level as Th1 response and IL-10 as Treg response in the period of the study.

BCG has also been used for decades to boost immune system in fight against gallbladder cancer, as immunotherapy:

https://www.cancer.org/cancer/bladder-cancer/treating/intravesical-therapy.html

https://my.clevelandclinic.org/health/treatments/17908-bacillus-calmette-guerin-bcg-treatment-for-non-muscle-invasive-bladder-cancer

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427258/


So given that

a) we know the safety profile of BCG, and people can evaluate if they're at risk of any adverse reactions (largely minimal) from getting it, and

b) it does seem to boost immune system, broadly and against the upper tract respiratory infections in the elderly (in addition to many other studied benefits for youth)


It seems that the negative costs of getting it (refreshed) are nearly 0, whereas the benefits are >0 and potentially great. On this basis, the recommendation makes sense, IMO (for anyone who isn't at a risk of some complication from BCG, based on the safety profile).

Comment by tb_throwaway on Coronavirus: Justified Practical Advice Thread · 2020-03-30T04:35:02.380Z · LW · GW

There's a theory that BCG vaccine (TB) helps strengthen you against corona, I'd recommend getting it if you haven't, or especially for your older relatives (given that the cost/side effects is well-understood and near-zero, whereas the benefits based on the below could be serious):

https://www.mpg.de/14610776/immune-boost-corona-virus https://www.sciencemag.org/news/2020/03/can-century-old-tb-vaccine-steel-immune-system-against-new-coronavirus

https://foreignpolicy.com/2020/03/24/coronavirus-vaccine-health-care-workers-bcg/
https://www.france24.com/en/20200326-australians-trial-tb-vaccine-to-fight-coronavirus
https://www.medrxiv.org/content/10.1101/2020.03.24.20042937v1
(looking at the correlation between vaccination rates by country and corona spread).

Very speculative: there are different strains of BCG, and allegedly the old (Soviet/Japan/Brazil) type/types is better. This could theoretically explain the different corona case loads between West/East Germany and between Japan + Thailand + Taiwan vs China + Iran (different vaccine strains).


Here are images showing differing corona case loads between East/West Germany (East uses/used the Soviet vaccine), supposedly the population density does not explain this (though note travel patterns, testing rates, etc. are probably all different):


https://upload.wikimedia.org/wikipedia/commons/thumb/a/af/COVID-19_outbreak_Germany_per_capita_cases_map.svg/1024px-COVID-19_outbreak_Germany_per_capita_cases_map.svg.png

https://1.bp.blogspot.com/-gy6Hqe8f2aM/Xn1KqOJ5wII/AAAAAAAA0EQ/rIhBVz2uM5A1q3lH3FFGnsXeTTTyjVpZgCLcBGAsYHQ/s1600/germany.png


Much more at https://www.jsatonotes.com/2020/03/if-i-were-north-americaneuropeanaustral.html?fbclid=IwAR2MKAgIt2IRjPSf_S9F4HozW4z7BWjH9_9D5p3RmGGJtdh2wp5gkpdzOj8&m=1. If someone who actually understands vaccines could read this and provide thoughts and vet, that'd be great. If it does end up making sense, please do spread, given the high expected value benefit here. I just don't know how easy it'd be to find old (Soviet etc.) style vaccines in the West.