BC HEALTH
Saved by @CodyyyGardner

Essential reading for intensivists: things you didn't even dream were going on in your ventilated patients' lungs. With credit to @robertpdickson who does some very clever translational work on lungs

 Firstly, we are aware of the inherent badness of oxygen. Here is protein content in alevoli after 48 hours of FiO2 95% (i.e. oedema), delightful.
Secondly, all those VAP's we get cross with (can someone silver impregnante the ET tube or something) that we think is just orally communicating flora/immunosuppression? Mais non. High FiO2 all but destroys weakling bacteria, leaving the redox-armoured king, staph aureus, to rule
Unmitigated staph surges and produces a truckload of PAMPs (pathogen associated molecular patterns). Being redoxically armoured, it is fairly happy to thwart oxidative burst from neutrophils attempting to kill them too.
Indeed the lung flora changes prior to the alveolar protein content - like both a canary in the coalmine moment, and then contributing to pathology.
As you'd expect, the usual criminals are involved in whipping up lung injury by the 48 hour mark
So, we have been breeding oxidation resistant pneumonia, brilliant. Does that mean people above a certain FiO2 should get prophylactic antibiotics? I mean, germ free mice don't get the same severity lung injury...
Graphs below: show less alveolar protein/immunoglobulin after 48-72 hours of FiO2 95%, and more nicely retained alveolar histology in germ free mice
On the other hand, as if that wasn't confusing enough, there is also a problem with gut microbiome and lung injury. How upsetting.
The gut microbiome changes later than the lung.
If you do give systemic antibiotics (this study used ceftriaxone and vancomycin all of which we use in ITU in UK) you make things much worse :O
BUT WHY YOU JUST TOLD ME STAPH WAS TAKING OVER AND NEEDED KILLING. Well, when you give these antibiotics you especially get rid of clostridia species in lung and gut. In gut, clostridia provides butyrate for colonocytes. When they don't get butyrate
they start to respire anaerobically, leaving gut lumen oxygen higher, meaning enterobacteriae go whoosh, and take over gut. In lung, staph goes whoosh. And no doubt it's the ceftriaxone resistant version of staph that does.
As a side note, the mechanisms that staph use to resist oxidative damage are the ones we use - superoxide dismutase, thioredoxins, flavins, DNA protection. But we only have this sufficiently available during the DAY and we don't have good anti-ox at NIGHT
which is why bad idea to have big brain bleed full of oxygenated Hb at NIGHT because the heme and the oxygen mess you up, especially badly.
Original paper here https://t.co/za56C6ET0I
As usual, understand less than when I started, about good lung care in ICU.
starting point for circadian difference sub arach https://t.co/VkoLf4teK5
starting point for circadian difference in bleomycin toxicity https://t.co/F16IoZ4jpi

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Tony Breu
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1/16
Why do B12 and folate deficiencies lead to HUGE red blood cells?

And, if the issue is DNA synthesis, why are red blood cells (which don't have DNA) the key cell line affected?

For answers, we'll have to go back a few billion years.


2/
RNA came first. Then, ~3-4 billion years ago, DNA emerged.

Among their differences:
🔹RNA contains uracil
🔹DNA contains thymine

But why does DNA contains thymine (T) instead of uracil (U)?

https://t.co/XlxT6cLLXg


3/
🔑Cytosine (C) can undergo spontaneous deamination to uracil (U).

In the RNA world, this meant that U could appear intensionally or unintentionally. This is clearly problematic. How can you repair RNA when you can't tell if something is an error?

https://t.co/bIZGviHBUc


4/
DNA's use of T instead of U means that spontaneous C → U deamination can be corrected without worry that an intentional U is being removed.

DNA requires greater stability than RNA so the transition to a thymine-based structure was beneficial.

https://t.co/bIZGviHBUc


5/
Let's return to megaloblastic anemia secondary to B12 or folate deficiency.

When either is severely deficient deoxythymidine monophosphate (dTMP*) production is hindered. With less dTMP, DNA synthesis is abnormal.

[*Note: thymine is the base in dTMP]

https://t.co/AnDUtKkbZh
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On December 29 we were dillucidating here if the drops meant "surprise, relatively neutral expression" or "a negative expression, horror" (Remember: https://t.co/J2gjQjAENw ). Well, December 22 drops seem to clarify it. First, the December 29 drop that generated the confusion 1/*


didn't appear in today drops, while several old ones have been posted again. I would say that all December 22 drops regarding facial expression mean and clarify "surprise". 2/*


More 3/*


And more. So, they didn't point to a negative event, just to one that generates surprise. 4/*


All these drops were completed with a Christmas gift one, confirming the surprise neutral meaning and adding a related positive one connected to the surprise. 5/*
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Ashtangha Yoga or the eight limbs of Yoga-


Many people think Yoga is just an Indian physical exercise but that's wrong. Yoga is a way to connect with the Supreme in Hinduism and attain Moksha(liberation).
The proper yoga as described in Hindu scriptures consists of 8 limbs:

1) Yamas- They are the 5 ethical rules of Hinduism. The 5 Yamas are:
i) Ahimsa: Nonviolence (this also includes not eating meat)
ii) Satya: truthfulness
iii) Asteya: non-stealing
iv) Brahmacharya: chastity, sexual restraint
v) Aparigraha: non-avarice, non-possessiveness

2) Niyamas- They are the 5 "do's". The five Niyamas are:
i) Shaucha: purity of mind, speech and body
ii) Santosha: contentment
iii) Tapas: austerity, self-discipline
iv) Svadhyaya: study of Vedas(Holy books of Hindus)
v) Ishvarapranidhana: contemplation of the Ishvara (God)

3) Aasana or the physical yoga-
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Starks\u262a\ufe0f\U0001f1f9\U0001f1e9
Starks☪️🇹🇩...
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Thread on how atheism leads to mental retardation (backed with medical citations🧵💉)

To start with, atheism is an unnatural self-contradicting doctrine.

Medical terminology proves that human beings are naturally pre-disposed to believe in God. Oxford scientists assert that people are "born believers".

https://t.co/kE0Fi588yn
https://t.co/OqyXcGIMJn


It should be known that atheism could never produce an intelligently-functioning society and neither ever will.

Contrastingly, Islam produced several intellectuals & polymaths, was on the forefront of scientific development, boasting 100% literacy


It is also scientifically proven that atheism led to lesser scientific curiosity and scientific frauds, which is also why atheists incline to pseudo-science.

Whereas, religion in general and Islam in particular boosted education.

https://t.co/19Onc84u3g


Atheists are also likely to affected by pervasive mental and developmental disorders like high-functioning autism.

Cognitive Scientists and renowned Neurologists found that more atheism is leads to greater autism.

https://t.co/zRjEyFoX3P
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Dr. Tory Eisenlohr-Moul, PhD \U0001f3f3\ufe0f\u200d\U0001f308
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Want to include the menstrual cycle in your scientific work, but aren't sure how to do it? My lab (@katjaschmalen) have just published an article on best practices for observational studies of the cycle! Thread below! 🧵

Despite decades of research on the menstrual cycle, empirical studies have not adopted consistent methods for operationalizing the menstrual cycle, resulting in confusion in the literature and limited possibilities to conduct systematic reviews and meta-analyses.

Below, I summarize this "how to" article, and relay some of the key points!

PARTICIPANTS: All participants should be naturally-cycling people with ovaries (remember that they are not necessarily "women"! 🏳️‍⚧️ ⚧).

We provide a Reproductive Status Questionnaire with rules for identifying naturally-cycling people (current function of the sexual organs and hormonal/other medications that stop the cycle).
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PAKISTAN-INDIA WATER ISSUES – HOW INDIA STOPPED WATER IN PAKISTAN's CANALS IN 1948

Thread

After partition in 1947, the water system was also bifurcated between Pakistan n India.

India cheated Pakistan when on April 1, 1948, India suddenly n without warning stopped...
1/n


...the supply of waters flowing into Pakistan's Central Bari Doab and Dipalpur Canals.

The boundary award on the partition of the sub-continent had left the headworks of these canals in Indian territory, and in accepting it India had implied her willingness to leave...

2/n


...the historic distribution of common waters undisturbed.

India's action was therefore in flagrant disregard not only of international law n morality, but of her solemn commitments with Pakistan and a gross violation of this country's historical rights over common waters.

3/n

Faced with a threat of utter desolation of millions of acres of fertile land, Pakistan had perforce to sign a document with India in which she agreed to "India's progressively diminishing water supplies to these canals and to the West Punjab government's tapping...

4/n

...alternative resources".

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5/n
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