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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
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
🚨Important changes to lockdown/self-isolation regulations from 5pm
The Health Protection (Coronavirus, Restrictions) (All Tiers and Self-Isolation) (England) (Amendment) Regulations 2021
£800 'house party' FPN & police can now access track & trace data
https://t.co/k9XCpVsXhC
“Large gathering offence”
As trailed by Home Secretary last week there is now a fixed penalty notice of £800 (or £400 if you pay within 14 days) for participating in an gathering of over 15 people in a private residence
Fixed Penalty Notices double for each subsequent “large gathering offence” up to £6,400
Compare:
- Ordinary fixed penalty notice is £200 or £100 if paid in 14 days
- Holding or being involved in the holding of a gathering of over 30 people is £10,000
Second big change:
Since September has been a legal requirement to sell-isolate if you test positive/notified by Track & Trace of exposure to someone else who tested positive
Police can now be given access to NHS Track & Trace data if for the purpose of enforcement/prosecution
This will make it easier for police to enforce people breaking self-isolation rules. Currently there has been practically no enforcement.
Data says only a small proportion of people meant to be self-isolating are fully doing so.
The Health Protection (Coronavirus, Restrictions) (All Tiers and Self-Isolation) (England) (Amendment) Regulations 2021
£800 'house party' FPN & police can now access track & trace data
https://t.co/k9XCpVsXhC
“Large gathering offence”
As trailed by Home Secretary last week there is now a fixed penalty notice of £800 (or £400 if you pay within 14 days) for participating in an gathering of over 15 people in a private residence
Fixed Penalty Notices double for each subsequent “large gathering offence” up to £6,400
Compare:
- Ordinary fixed penalty notice is £200 or £100 if paid in 14 days
- Holding or being involved in the holding of a gathering of over 30 people is £10,000
Second big change:
Since September has been a legal requirement to sell-isolate if you test positive/notified by Track & Trace of exposure to someone else who tested positive
Police can now be given access to NHS Track & Trace data if for the purpose of enforcement/prosecution
This will make it easier for police to enforce people breaking self-isolation rules. Currently there has been practically no enforcement.
Data says only a small proportion of people meant to be self-isolating are fully doing so.
Very important that obvious failures with Track and Trace and self-isolation (study late last year said 18% of people complying https://t.co/dhJUZ7Pm0l) are not painted as an enforcement issue. Plainly not. Would just pass buck to police who have almost no capacity to enforce https://t.co/Eb4Kl5Ze0E
— Adam Wagner (@AdamWagner1) January 25, 2021
You gotta think about this one carefully!
Imagine you go to the doctor and get tested for a rare disease (only 1 in 10,000 people get it.)
The test is 99% effective in detecting both sick and healthy people.
Your test comes back positive.
Are you really sick? Explain below 👇
The most complete answer from every reply so far is from Dr. Lena. Thanks for taking the time and going through
You can get the answer using Bayes' theorem, but let's try to come up with it in a different —maybe more intuitive— way.
👇
Here is what we know:
- Out of 10,000 people, 1 is sick
- Out of 100 sick people, 99 test positive
- Out of 100 healthy people, 99 test negative
Assuming 1 million people take the test (including you):
- 100 of them are sick
- 999,900 of them are healthy
👇
Let's now test both groups, starting with the 100 people sick:
▫️ 99 of them will be diagnosed (correctly) as sick (99%)
▫️ 1 of them is going to be diagnosed (incorrectly) as healthy (1%)
👇
Imagine you go to the doctor and get tested for a rare disease (only 1 in 10,000 people get it.)
The test is 99% effective in detecting both sick and healthy people.
Your test comes back positive.
Are you really sick? Explain below 👇
The most complete answer from every reply so far is from Dr. Lena. Thanks for taking the time and going through
Really doesn\u2019t fit well in a tweet. pic.twitter.com/xN0pAyniFS
— Dr. Lena Sugar \U0001f3f3\ufe0f\u200d\U0001f308\U0001f1ea\U0001f1fa\U0001f1ef\U0001f1f5 (@_jvs) February 18, 2021
You can get the answer using Bayes' theorem, but let's try to come up with it in a different —maybe more intuitive— way.
👇
Here is what we know:
- Out of 10,000 people, 1 is sick
- Out of 100 sick people, 99 test positive
- Out of 100 healthy people, 99 test negative
Assuming 1 million people take the test (including you):
- 100 of them are sick
- 999,900 of them are healthy
👇
Let's now test both groups, starting with the 100 people sick:
▫️ 99 of them will be diagnosed (correctly) as sick (99%)
▫️ 1 of them is going to be diagnosed (incorrectly) as healthy (1%)
👇
