BC HEALTH
Saved by @Mollyycolllinss

1/15
Why can cefepime cause neurological toxicity?

And why is renal failure the main risk factor for this complication?

The answer requires us to learn about cefepime's structure and why it unexpectedly binds to a certain CNS receptor.

#MedTwitter #Tweetorial

 2/
Let's establish a few facts about cefepime:

🔺4th generation cephalosporin antibiotic
🔺Excretion = exclusively in the urine (mostly as unchanged drug)
🔺Readily crosses the blood-brain barrier (so it easily accesses the brain)

https://t.co/rjYG1BfGPR
3/
The first report of cefepime neurotoxicity was in 1999.

A patient w/ renal failure received high doses of cefepime and then developed encephalopathy, tremors, myoclonic jerks, and tonic-clonic seizures.

✅All symptoms resolved after hemodialysis.

https://t.co/u7JLVitQpp
4/
Cefepime neurotoxicity is surprisingly common, occurring in up to 15% of treated critically ill patients (w/ symptoms varying from encephalopathy to seizures).

💡The main risk factors = renal failure and lack of dose adjustment for renal function.

https://t.co/nxbnzSq8AR
5/
What about cefepime induces neurotoxicity?

One clue is that it's not the only antibiotic that causes neurotoxicity, particularly seizures.

This actually is a class effect w/ other beta-lactam antibiotics (including penicillins and carbapenems).

https://t.co/Lf4BhON9IY
6/
Recall that beta-lactam antibiotics all share a common structural feature: a beta-lactam ring.

https://t.co/iWXweuG4Ct
7/
A 1971 study in cats implicated beta-lactam rings as the source of neurotoxicity.

High doses of penicillin were used to induce seizures.

🔑But pre-incubation w/ the enzyme beta-lactamase (disrupts the beta-lactam ring) blocked all seizure activity.

https://t.co/M3lDiXm88N
8/
So why can beta-lactam antibiotics like cefepime cause neurotoxicity?

It turns that they block the binding of the inhibitory neurotransmitter gamma aminobutyric acid (GABA) to its receptor.     

🔑Cephalosporins block GABA particularly effectively.

https://t.co/Eo0OlTduOE
9/
The GABA receptor has two subtypes (A and B), and the A subtype functions as a ligand-gated Cl⁻ ion channel.

Cefepime binds to the GABA-A receptor and blocks Cl⁻ influx, which correlates with its ability to induce seizure activity.

https://t.co/l2f9QHHEEW
10/
We've established that cefepime blocks GABA.

This induces neuro-excitation leading to seizures and other neurotoxic manifestations such as tremors and encephalopathy.

💡But why is there such a strong link with renal failure?
11/
An obvious explanation would be that, since cefepime is renally cleared, elevated serum and CNS drug levels build up.

This is supported by the observation that cefepime and other cephalosporins block GABA in a concentration-dependent manner.

https://t.co/l2f9QHHEEW
12/
But increased drug levels might not be the only reason that patients w/ renal failure are predisposed to neurotoxicity.

The milieu around neurons seems to matter as well.
13/
This experiment in rat brain slices simulated a "renal" milieu by using a hyperkalemic medium around neurons.

⚡️Exposure to higher potassium levels significantly increased the ability of cefepime to induce epileptiform discharges.

https://t.co/vb3p4xXdTm
14/
Let's ask one final question.

Why can cefepime (and other beta-lactam antibiotics) block the GABA receptor?

Exactly why hasn't been well-studied but it likely reflects sufficient structural similarity w/ GABA.

https://t.co/KN7I6ACXvb
15/
🧠Cefepime induces neurotoxicity by blocking the GABA receptor, similar to other beta-lactam antibiotics
🧠This results from structural similarities between GABA and the beta-lactam ring
🧠Renal failure = main risk factor b/c of ⬆️ drug levels +/- hyperkalemia

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@DrOlufunmilayo
HELLO: If you pee and every time you finish, your urine looks like this picture, you may have a serious medical illness.

Foamy urine especially if it is persistent and noticeable over time may mean you have a serious kidney problem.

Let’s talk about this today...
RT for others.


What are the features of a normal urine?

A normal urine should have a light yellow colour, painless, odourless (or faint smell), steady stream and should ideally not foam when you pee.

When there’s something wrong, then you see changes in all the above normal features of urine.

For instance if urine becomes very deep yellow, it may mean you are dehydrated;

If urine becomes painful or smells really really bad, it may mean you have an infection;

If urine has a poor stream, especially in a man, it may mean a prostate problem like cancer.

Do you get me?

So today let’s talk about Foamy Urine.

What are the things that can cause urine to suddenly be foamy. As I said in the first tweet, it MAY mean a serious medical illness like a serious kidney problem.

First things first- it does NOT always mean a problem but it may as well.

Now what are the causes of Foamy Urine:

1. SPEED-
If you pee really fast or with a lot of force, it may make your urine more foamy than usual. The speed and force makes the urine generate a lot of bubbles which tend to almost quickly disappear as it is formed in the toilet bowl.
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Stephen Wolfe
Stephen Wolfe
@PerfInjust
Thread:
I'm thinking about Tim Keller's influence.

There is the curious fact that Keller is well-regarded among the culture elite (or at least has not suffered the sort of vilification one might expect given his influence). How can we explain this?

Looking at Prodigal God and other writings, you see that his approach to urban ministry is deeply political in a way that appeals to Democrat-heavy cities. It involves two moves:

1) equalizing sins: elevating the sin of hypocrisy, "moralism," and "religion" (the sins of "conservatives") and equating these with the sins tolerated among liberal (e.g., homosexuality)
&
2) emphasizing "self-righteousness" as a sort of chief sin (the sin of "red states").

Keller effectively downplays the sins that liberals tolerate while elevating the sins of their political enemies, the red state conservatives.

But the greatest appeal to liberals is that critiquing the "self-righteous" vilifies political action, particularly the action of social conservatives (e.g., anti-gay marriage). And the equalization of sins eases concerns over changes in social policy (e.g., gay marriage).
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Gregg Gonsalves
Gregg Gonsalves
@gregggonsalves
I think @SamAdlerBell in his quest to be the contrarian on Fauci gets several things wrong here. 1/


First, the failure last year actually was driven by the White House, the #Trump inner circle. Watch what's happening now, the US' scientific and public health infrastructure is creaking back to life. 2/

I think Sam underestimates the decimation of many of our health agencies over the past four years and the establishment of ideological control over them during the pandemic. 3/

I also am puzzled why Tony gets the blame for not speaking up, etc. Robert Redfield, Brett Giroir, Deb Birx, Jerome Adams, Alex Azar all could have done the same. 4/

Several of these people Bob Redfield, Brett Giroir, Alex Azar were led by craven ambition, Jerome Adams by cowardice, but I do think Deb Birx and Tony tried as institutionalists, insiders to make a difference. 5/
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Nyx
Nyx
@Nix_468
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-
Asana is a posture that one can hold for a period of time, staying relaxed, steady, comfortable and motionless. The aasana postures are believed to have been given by Mahadeva (Hindu God) himself. Hatha Yoga Pradipika mentions 84 aasanas.
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Starks\u262a\ufe0f\U0001f1f9\U0001f1e9
Starks☪️🇹🇩...
@MegaIntelIect
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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Very famous Krishna Mandir where Bankey Bihari Ji is worshipped and looked after as a child.
Bankey means “Bent at three places”.
Thakur Ji was worshipped in Nidhivan till 1863. This mandir was constructed in 1864 by Goswamis.
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Legend says that Swami Haridas used to worship Krishna in Nidhivan.
Once, his curious disciples entered the forest but they were almost blinded by bright, intense light. Upon knowing this, Swamiji himself went there and after his requests, Krishna appeared with his consort.


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The kingdom of Sindh was ruled by its last Hindu king Raja Dahir during the 8th century. When Muhammad-bin-Qasim invaded Sindh, he decimated Sindh in his savage bloodlust. The chronicles of his advent are described in the Chachnama.


2/n
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3/n
When Muhammad-bin-Qasim attacked Sindh, Dahir had collected an army of 50,000 horses and marched from Brahamanabad to Rawar to face the invader. Qasim had an army that numbered in the tens of thousands with camels & horses.

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Earlier Arab Alafis - Syeds from Prophet Mohammed’s own family had fled from Mecca with 500 men to Sindh and Raja Dahir had given them asylum. Trusting these Muslims would prove to be the fatal mistake for the downfall of Sindh & pave the way for Islamic invasion.

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