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Recent comments (see more)

... niboonsh made a comment (nbme21)
 +59  submitted by niboonsh(409)

https://www.youtube.com/watch?v=4-DuvwoH2zQ if ur lazy like me, this is a good refresher video

d_holles  Amazing video dude. Somehow never learned this in neuro lol. +7
aag  Awesome video! Is this why you can give Mg2+ to eclampsia patients, because if so, mind goddamn blown. +4
... drdoom made a comment (nbme21)
 +58  submitted by drdoom(1205)

The synthesis of virtually all proteins (mRNA->peptide) occurs in the cytoplasm.[1] That’s where all ribosomes reside, after all. Ribosomes, which are mostly just rRNA (~2/3 rRNA + 1/3 protein*, by weight), are assembled in the nucleus but only do their stuff once they get to the cytoplasm.

For a protein to leave its original hometown of the cytosol and become a resident of the nucleus or, say, the endoplasmic reticulum, it needs to have a little string of amino acids which shout “I belong in the nucleus!” or “I belong in the endoplasmic reticulum!”

Proteins ultimately destined for the ER contain an unimaginatively named string of amino acids known as “signal sequence,” which, for the purposes of the Step 1, is always at the N-terminus. The signal sequence tells other cytosolic proteins, “Hey! Take me (and the rest of the peptide of which I am part) to the ER!”

In the absence of this signal, a protein will remain in its “default” home of the cytosol.

Here’s a nice schematic showing the flow of proteins from initial synthesis to final destinations:


Endnotes

  1. “The synthesis of virtually all proteins in the cell begins on ribosomes in the cytosol.” (Essential Cell Biology, Alberts et al., 2014, p. 492)

*If you really want your mind blown, consider that even the protein subunits that make up that 1/3 of a ribosome are themselves initially synthesized in the cytosol; later, they are transported back into the nucleus via the nuclear pore.

qball  Awesome explanation. Now explain it to me like I'm 5. +13
drdoom  All baby peptides are born in the cytosol. But some baby peptides have a birthmark at their N-terminus. The birthmark tells a special mailman that this baby needs to be delivered somewhere else. If you chop off the birthmark — or erase it somehow — the mailman never knows to take baby to its true home. The end. Now go to sleep or Santa won’t bring your presents. +83
... drachenx made a comment (nbme24)
 +56  submitted by drachenx(72)

These kinds of questions are really hard because I've never seen female reproductive structures irl. :c

nbmehelp  Lmao +3
regularstudent  Lmao +1
mutteringly  Lmao +
rockodude  lmao +
abkapoor  Lmao +
dang90  LMao +
icrieeverytiem  lmao +
peteralamir  Lmaoo +
... drdoom made a comment (nbme24)
 +56  submitted by drdoom(1205)

The duodenal lumen (and pancreatic proteases like CHYMOTRYPSIN) is the site where pancreatic enzymes (“endopeptidases”) cleave large polypeptides into smaller bits (=dipeptides,tripeptides). It is at the BRUSH BORDER where the smallest kinds of peptides (dipeptides,tripeptides) are broken down into their amino acids, which finally can be co-transported with Na+ into the intestinal cell.

I think about it this way:

  • stomach acid denatures and “opens up” proteins (without specific cleavage);
  • pancreatic enzymes then cleave denatured polypeptides into smaller bits;
  • brush border enzymes finally break down tiniest peptides into absorbable amino acids.
regularstudent  Isn't the brush border still part of the intestinal lumen? Don't the amino acids enter into the intestinal cell (the "intestinal mucosa")? +1
drdoom  @regularstudent No, the lumen is literally the cavity—the empty space. +2
jj375  Still annoyed about this question, but here is a schematic in case it helps anyone else: https://doctorlib.info/physiology/medical/medical.files/image1890.jpg +2
drdoom  @jj375 best schematic i’ve seen so far. superb. +2
... seagull made a comment (nbme22)
 +52  submitted by seagull(1933)

Which of the following reasons is why this question is bull?

1) Using the word "cyclic" instead of tricyclic for clarity

2) Knowing all of epidemiology of all drugs

3) having to reason out that anticholinergic effects are probably the worst over alpha1 or H1 effects to no certainty.

4) The crippling depression of studying for days-to-weeks on end to probably do average on the test.

nlkrueger  yo, re-fucking-tweet +26
aesalmon  I agree, I picked H1 because such a common complaint for those on TCAs is Sedation, I figure it might be so commonly seen as to be the "most common" reason for noncompliance. I suppose the "hot as a hare...etc" effects would be more severe/annoying, but I didn't think they were more common. +4
fcambridge  I just like to pretend that there's a reason this question is now in an NBME and no longer being used for the test. Hopefully they realized the idiocy of this question like we all do +1
link981  Since it said cyclic, I thought of using, discontinuing, then using again. These people who write these questions need take some English writing courses so they can write with CLARITY. Cyclic is not the same as Tricyclic. +6
waterloo  Incredibly awful question. one thought I did have when deciding between anticholinergic and antihistaminic - nortriptyline and desipramine are secondary amines that have less anti-cholinergic effects (from Sketchy Pharm) so maybe that's what they were getting at? That someone went out and made a new TCA drug that would have less anticholinergic effects. +
victor_abdullatif  This isn't testing drug epidemiology; it's actually asking "which of these side effects are caused by TCAs and would be the worst to experience?" +
tekkenman101  "worst to experience" is incredibly subjective lmao. +1
... lsmarshall made a comment (nbme24)
 +47  submitted by lsmarshall(465)

Urea Cycle Disorders > Isolated severe hyperammonemia (> 1000; i.e., no other severe metabolic disturbances

Ornithine transcarbamylase deficiency > (most common urea cycle dis.) orotic acidemia/aciduria, hyperammonemia

Organic Acidemias > Hyperammonemia, anion-gap acidosis, ketosis (from hypoglycemia)

Medium-chain acyl-CoA dehydrogenase deficiency > Hyperammonemia, hypoketotic hypoglycemia (seen in β-oxidation disorders, EXCEPT adrenoleukodystrophy)

Liver dysfunction > Hyperammonemia, LFTs messed up, older pt.

lsmarshall  Summary of metabolic issues relating to hyperammonemia +9
seagull  i'm leaning towards Ornithine transcarbamylase deficiency. +3
notadoctor  Not sure why this isn't considered a mitochondrial disorder since the issue is Ornithine transcarbamylase deficiency in the mitochondria? +2
charcot_bouchard  if it was mitochondrial disorder no one would escape +3
wowo  figure in OTC deficiency, they might have to explicitly mention the orotic aciduria AND typically presents earlier, around 24-48hrs of life after they've fed (at least per BB) + also per BB, propionic acidemia and MM acidemia have an onset of weeks to months and lead to build up of organic acids --> acidemia in addition to hyperammonemia (not sure why, but several aa enter the TCA cycle via propionyl CoA --> methylmalonyl CoA --> succinyl CoA, but now this is defunct d/t enzyme deficiencies...?). Anywho, propionic acidemia described on FA2019 p85, but doesn't list hyperammonemia +2
artist90  i think it cannot be Ornithine transcarbamylase deficiency bc it is XR disease. this pt has a healthy 2yr old brother which rules out X-linked recessive disease correct me if i m wrong +7
artist90  it is 100% Propionic acidemia Uworld Q-id: 1340. it is an exact copy question of uworld. i got it wrong bc i forgot these are organic acids. But i am still confused on 2 things 1-how does acidosis cause Hypoglycemia and Ketosis. 2-why is Ammonia elevated in these pts bc urea cycle will be fine? +2
yb_26  1) hyperammonemia is seen in all urea cycle disorders except arginase deficiency 2) organic acids directly inhibit urea cycle => hyperammonemia (from UWorld) +2
yex  According to UW, there is another question # 1341. This one refers to methylmalonic acidemia (ORGANIC ACIDEMIA). HYPOGLYCEMIA results from overall increased metabolic rate leading to increased glucose utilization and direct toxic (-) of gluconeogenesis by organic acids. The presence of hypoglycemia leads to increased free fatty acid metabolism that produces KETONES, resulting in a further anion gap met acidocis. Finally, organic acids also directly (-) the urea cycle, leading to HYPERAMMONEMIA. +19
ih8payingfordis  I think there has been some confusions because FA does a poor job integrating these concepts together but here are some references: FA 2019 pg 85: Propionic Acidemia (this is one example of organic acid metabolism disorder) In the summary figure on Pg 74, look at the protein metabolism (located bottom right). Basically, you can have disorders where you have Propionyl-CoA buildup alone OR Proionyl-CoA and Methylmalonyl-CoA buildup. And these organic acidemias are autosomal recessive in their inheritance pattersn, which fit with the stem we're given (ie XX individuals can be affected) One thing that UW state that I do not have an explanation for: the buildup of organic acids inhibit the urea cycle hence the increase in ammonia (anyone knows how this happens?) +
aaftabsethi1  Can someone tell me why not MELAS ? +1
jaramaiha  @aaftabsethi because all of the siblings would show some symptoms if it were to be a mitochondrial disease. Which his brother is healthy, and sister was full-term but died due to unspecified causes. +
utap2001  Why acidosis cause Hypoglycemia and Ketosis and hyperammonia? In acidosis(such lactic acidosis)-> indicate body energy crisis -> inc. glycolysis, Hypoglycemia-> inc. protein breakdown, Hyperammonia -> dec. TCA cycle, Ketosis +
... azibird made a comment (nbme24)
 +47  submitted by azibird(279)

Who else came here after getting triggered by this answer?

yousif11  This question did not age well +23
helppls  I'm going to be taking Step with this song stuck in my head lol +
... tea-cats-biscuits made a comment (nbme24)
 +46  submitted by tea-cats-biscuits(273)

Mast cells degranulate, producing histamine which attracts eosinophils. The early stage of an allergic reaction is mast cell mediated, but the late stage (including mucus production) is mediated by eosinophils.

atstillisafraud  Thanks for a good answer. This question made me feel like I was taking T21 pills +18
medguru2295  Thank you- I was really thinking this question had 2 correct answers... of course my dumbass picked Mast cells. +7
ajss  where do i find this info?? +
paperbackwriter  @ajss pg 112 of first aid 2019, under type I hypersensitivity. Immediate --> mast cells releasing histamine and tryptase, late--> eosinophils and leukotrienes recruited via chemokines +3
graciewacie9  Wow, i missed the fact that the question is asking for the RESULT of the reaction, NOT the cause of the reaction. Mast cells cause the initial reaction, eosinophils would be the result of the eosinophils. *facepalm +9
greentea733  @graciewacie9 SAME UGH +
lba9587  Pathophys (as far as I understand it)...Mast cell degranulates, thus the phospholipid bilayer et. Al are left behind and needs to be degraded. Who comes in? Our good friend eosinophils, as they contain Major Basic Protein (responsible from breakdown of expired mast cell). Note, you can tie this in to the delayed Leukotriene effects of an allergic rxn, as the bilayer is also broken down by arach. Acid. (See this link to support my credibility https://images.app.goo.gl/3cUF3ZVc7qy8uxAi9) +
mutteringly  who else looked up what T21 pills were +8
fatboyslim  Who else still doesn't know what T21 pills are and feels left out? +
... sympathetikey made a comment (nbme24)
 +46  submitted by sympathetikey(1600)

Everyone who got this question right is a cop. ༼⌐■ل͟■༽

dr_ligma  Fkn narcs +2
j44n  whippet_gang +
... amorah made a comment (nbme20)
 +46  submitted by amorah(115)

Fever -> rule out left ventricular failure TMP-SMX prophylaxis -> rule out Pneumocystis jiroveci Kidney transplant but no WBC/RBC in urine -> rule out transplant rejection

Leaving CMV and atypical mycobacterium as the remaining two options. CMV is more likely in a transplant patient.



Help your fellow humans! (see more)

drdoom asks (nbme25):
Do session tokens invalidate? If I try to submit this comment later is it invalidated? Try later. help answer!
brawamigonnagetthismd asks (nbme25):
Why? I though the bicep reflex would be strongest since it was not involved with the radial nerve issue. help answer!
brawamigonnagetthismd asks (nbme23):
Wait, adipose tissue scars?? What the heck is this? maybe it's that 'fibro' part...Watched all that Botched for nothin' help answer!
tamarafainblout asks (nbme16):
why cant it be A? Aren't melanocytes derived from neural crest cells? help answer!
gigantichawk asks (step2ck_free120):
Was anyone thinking calcium pyrophosphate? Inflammatory joint, patient with RA, no organisms seen on FNA, would be treated with steroids? help answer!
gigantichawk  "Septic arthritis may be definitively established in the setting of positive synovial fluid Gram stain/culture. In patients with purulent synovial fluid (leukocyte count 50,000 - 150,000) but negative synovial fluid cultures, a presumptive diagnosis of septic arthritis can be made." Acute Calcium Pyrophosphate deposition would typically have a leukocyte count of 15,000 - 30,000 on aspiration. +
305charlie94 asks (step2ck_form7):
Shouldn't early salicylate OD cause resp alkalosis? I thought only late salicylate OD caused increased anion gap metabolic acidosis. I chose Methanol given her eye sxs and I thought aspirin should be ruled out due to the timing of her OD help answer!
azibird asks (step2ck_form8):
What does "central hilar opacification bilaterally" on x-ray represent? help answer!
sorrel1000  @azibird that confused me too. I was thinking sarcoidosis and then put constrictive pericarditis down. But now looking back, there wasn't enough support for sarcoidosis. +1
azibird asks (step2ck_form8):
What is that black sliver on here retina? help answer!
notyasupreme asks (step2ck_free120):
What a dumb question, there's literally a UWorld question about how a girl with a hx of seizures faked one and how you need to do neuro testing if they have no post-ictal confusion. I'm sorry, why are we even entertaining this if she has NO post-ictal confusion? help answer!
notyasupreme asks (step2ck_free120):
I'm sorry but how the hell are you supposed to know it's vulvar when it says nothing about the vulva. I was between that and polyps, but put polyps because it was on the perineum? Like how the hell is that the vulva? help answer!
notyasupreme  lol jk, just looked it up and apparently I know shit about the female anatomy! +
jj375  I was quite confused by this too, especially since it said vulva but then said anal verge, but then also said vaginal bleeding. Here is a photo in case anyone else needs it: https://healthcare.utah.edu/huntsmancancerinstitute/gynecologic-cancer/images/vulvar-anatomy-image.jpg +
azibird asks (step2ck_form7):
Agree that this question sucks. Why not go for psychodynamic psychotherapy since the patient specifically says she would like to understand why she does these things? Not a great option but still... help answer!
adong asks (step2ck_form8):
they really copied and pasted this sh!t on nbme 6-8 huh? couldn't afford another heart sound smh help answer!
adong asks (step2ck_form7):
they really copied and pasted this sh!t on nbme 6-8 huh? couldn't afford another heart sound smh help answer!
notyasupreme asks (step2ck_form6):
Cardi B voice: WHAT WAS THE REASON for the goddamn Gram - stain, like whyyyyyyyyy. That's why I put prostatitis, even though the non-tender prostate threw me off. Damn, these questions are really just read the first and last sentence huh? help answer!
notyasupreme asks (step2ck_form6):
I think I thought too deep into this, but isn't the cause of post-op fever on days 3-5 UTIs? I just remembered the mnemonic, but I guess I was thinking too deep.. help answer!
abelaia  probably classic overthink. likely to do with the type of blood culture grown. Staph vs. E. coli. +
groovygrinch asks (step2ck_form7):
I thought with the whole <6 months or less thing he would qualify for hospice care in a skilled nursing facility? I am the only one who thinks it's a dick move to question this guy's decision making? help answer!
epiglotitties asks (nbme20):
This isn't the scenario in this question, but I was wondering what would happen if you had told the parents the diagnosis and they didn't want their child to know? help answer!
yogurt-dimple asks (nbme25):
Am I crazy, or does the question stem imply that this was inherited paternally? help answer!
raspberry-muffin  In this question sounds like inherited paternally , but this muscle biopsy confirmed Mitochondrial inheritance. Muscle biopsy: Immunohistochemistry typically shows ragged red fibers, which are caused by sub-sarcolemmal and inter-myofibrillar accumulation of defective mitochondria in muscles (mitochondria stain red). Probably Mother has the same condition too. +
yogurt-dimple  Gotcha. Yeah, the red ragged fibers tipped me off to mitochondrial myopathy, but because the stem implied paternal inheritance, I figured there was just another disease I had forgotten about that presents with them. +
drdoom  @raspberry-muffin I'm not convinced. It is highly unlikely the NBME would write this question and expect you to "assume" mom has condition without making any mention of mom. Plus, it is simply highly improbable that myopathy is present in both mom and dad lineage. That seems off to me. +
drdoom  @yogurt-dimple, I think this a key line in the explanation: “However, there are additional mutations that affect mitochondrial RNA translation, trafficking and incorporation of respiratory protein complexes, and maintenance of the inner mitochondrial membrane that can also lead to mitochondrial myopathy.” +
drdoom  Yes, they say, "Mitochondrial diseases are strictly inherited through the mother" but this is not a mitochondrial disease — this is a "non-mitochondrial–derived" mitochondrial myopathy; yes, mitochondria are affected but the mutation is in somatic (nuclear) genes that govern the maintenance of "healthy mitochondria". This is because the mutation affects the function/operation of mitochondria but the mutation itself is in the nuclear DNA (which control something about the "quality" of mitochondria but what exactly is not yet known). +
shelbinator94 asks (nbme18):
Why couldn't this be branching enzyme impairment? They both cause cardiac symptoms (according to Amboss at least) help answer!
kms123 asks (free120):
can someone explain why it's not degranulation of eosinophils? help answer!
fhegedus  Eosinophils (FA 2020 page 408) are involved in type I hypersensitivity reactions (asthma, allergy, analphylaxis), parasitic infections and other pathologies. They are not involved in edema formation. I hope this helps! :) +
fhegedus  Also, the patient in the question got a laceration, which probably led to a bacterial infection; so neutrophils would be predominant, not eosinophils. +
kms123 asks (nbme22):
How would we rule out antithrombin deficiency? help answer!
sd22  PT, PRT, and TT normal in antithrombin deficiency. FA ‘20 pg. 428 +
sd22  PTT* lol autocorrect clearly hasn’t been studying +
calvin_and_hobbes asks (nbme21):
This Q stem was confusing to me because I thought pain>>itch for shingles. Any thoughts? help answer!
calvin_and_hobbes asks (nbme21):
"In addition to slightly decreased platelet count..." — why are plts slightly low in EBV infection/mono? help answer!
empem28 asks (nbme22):
totally buy the answer of K+ being increased, but can somebody explain why her extreme dehydration (decreased skin turgor, excess urine output) wouldn't lead to an increase in serum [Na+]? help answer!

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