"That which cometh out of the mouth"

I have another new theory. No, it's not exactly received medical wisdom. That's what makes it new. :D

In the past few days, I've learned a lot about how atherosclerosis (plaques building up on artery walls) can lead to stroke. I had previously hazily envisioned strokes being caused by a blood clot that just magically appeared in the brain. To the contrary, the blood clot generally comes from somewhere besides the brain. Typically, an atherosclerosis-related stroke-causing blood clot originates in the carotid arteries, right at the point where the carotid artery divides into two arteries, the internal carotid artery and the external carotid artery. Atherosclerotic plaques build up in the vicinity of that "Y"-shaped fork, and rupturing of the plaques triggers formation of a blood clot which then moves up into the head and gets stuck in a smaller artery in the brain.

What causes plaques in the first place? An influential theory is that oxidized LDL cholesterol starts the process of atherosclerosis. (https://academic.oup.com/cardiovascres/article/68/3/353/309912/Oxidized-LDL-a-critical-factor-in-atherogenesis) My questions then are 1) how does the LDL get oxidized and 2) why does it cause plaques right at that carotid junction?

First I looked into what causes the oxidization. A major culprit behind oxidizing of LDL is hypochlorous acid produced by the enzyme myeloperoxidase, which uses hydrogen peroxide (H2O2) and a chloride ion (Cl-) to do so. (https://link.springer.com/article/10.1007/s12170-013-0291-3, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315351/, http://onlinelibrary.wiley.com/doi/10.1002/biof.5520060208/abstract, http://atvb.ahajournals.org/content/20/7/1716.long?related-urls=yesl20/7/1716)

H2O2 is supposed to be broken down in our bodies by catalase, glutathione peroxidase, and peroxiredoxins. Glutathione peroxidase activity appears to decrease as we age. (https://www.ncbi.nlm.nih.gov/pubmed/18511755) It's not clear exactly why, but our ability to break down H2O2 with our saliva appears to go down by approximately half as we age (https://academic.oup.com/biomedgerontology/article/62/4/361/629357/Age-Related-Changes-in-Salivary-Antioxidant), which means that there is likely going to be some extra H2O2 in our mouths in our later years. Excess H2O2 is harmful to gum tissue (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730038/), and in the gum tissue H2O2 can apparently diffuse in such a way as to end up in the jugular vein (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3745256/).

The jugular vein travels down through the neck, taking all the "used" blood from the head back to the heart. In the neck, the jugular vein is covered by the carotid sheath, which holds the jugular vein next to the carotid artery. My novel hypothesis is this:

Excess aging-related H2O2 from the mouth goes into the jugular vein and then makes its way over to the carotid artery next door, boosting the amount of oxidized LDL in the carotid artery just before it hits the "Y"-shaped fork, where the oxidized LDL hits the sides of the branching arteries and starts the process of forming atherosclerotic plaques. 

I think the weakest link in my theory is that I can't find a lot of clear proof that H2O2 can migrate from a vein into a neighboring artery; however, it does seem to be generally accepted that H2O2 diffuses through tissues:

It is now widely accepted that this low molecular weight molecule is utilized in metabolic regulation in ways similar to diffusible gases such as NO, CO, or H2S. Even more so, H2O2 is recognized as being in the forefront of transcription-independent signals, in one line with Ca2+ and ATP. H2O2 diffuses through tissues to initiate immediate cellular effects, such as cell shape changes, the formation of functional actomyosin structures, and the recruitment of immune cells.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979367/

I suppose this will have to suffice for now. It's time to go eat dinner with my family...a nice, low-fat, high-soluble-fiber, and antioxidant-full meal.

(I almost forgot to explain the title of my post. In Matthew 15:11, it is recorded that Jesus said, "Not that which goeth into the mouth defileth a man; but that which cometh out of the mouth, this defileth a man." My research above points to oxidizing substances from the mouth contributing to the formation of atherosclerotic plaques in the carotid arteries.)

Possible transient ischemic attack

My husband, who is barely "middle-aged," experienced something on Tuesday that appears to have been a transient ischemic stroke (TIA), which is considered a warning mini-stroke. He'll be getting a possible-TIA workup done at the hospital in the next few weeks, and he has begun taking a baby aspirin daily.

This is a man who is at a healthy weight and who cycles about 25 miles per week. He doesn't smoke, drink alcohol, or use drugs. He is, however, cursed genetically (his grandfather died at age 45 of an enlarged heart) and likes desserts and fast food pizza too much.

The episode happened within 24 hours of a daughter's birthday party, which featured triple meat pizza from Little Caesar's, birthday cake made with lots of butter, and ice cream. And we think he had an egg for breakfast the following morning. He has had high cholesterol and triglycerides for years, but he had hoped to stay healthy by dint of lots of exercise and fruits and vegetables. It looks as though he'll also have to largely cut out some favorite treats, too, though. :(

On the bright side, he did escape the illness I posted about last time.

H1N1?

Over the past five days, 6/7 family members have been struck with a cold or flu virus. Because it started with an intense sore throat for me, I thought it might be strep throat, but the tell-tale symptoms in the throat never showed up. What was weird was that instead of a bunch of coughing and sneezing initially, it started with a day of fatigue just lying in bed with no/little hunger. I found out last night that friends from our church congregation have confirmed H1N1 ("swine") flu. I compared H1N1 symptoms with the symptoms we have, and they seem to be a pretty good fit.

So life is on hold for us while everyone rests. Except for Daddy, who insists he'll escape it, we're self-quarantined at home. The heat is turned up, and the air humidifier is turned up. I'm also taking a lot of melatonin to see if it helps shorten the course of the illness. I felt better yesterday, so I stayed up to my normal time (past 11 pm). I ended up regretting that, so I don't think just taking melatonin is an adequate substitute for insufficient rest. The evidence I found last year did only point to melatonin being possibly helpful for avoiding ARDS (acute respiratory distress syndrome), and I have to admit, my lungs seem to be doing OK. So maybe there's merit still to my hypothesis, but right now I'm dissatisfied with anything that doesn't make me feel better immediately.

A definition with a difference

I don't care to get political on my blog for the most part. I'm bending my usual course today for a very good legal reason, which I'll lay out below.

On January 27, President Trump signed an executive order temporarily staying entry under the Immigration and Nationality Act (INA) for aliens (i.e., non-citizens and non-nationals of the USA) from countries previously identified as being of higher risk due to harboring/sponsoring of terrorists. Here's the relevant paragraph:

    (c)  To temporarily reduce investigative burdens on relevant agencies during the review period described in subsection (a) of this section, to ensure the proper review and maximum utilization of available resources for the screening of foreign nationals, and to ensure that adequate standards are established to prevent infiltration by foreign terrorists or criminals, pursuant to section 212(f) of the INA, 8 U.S.C. 1182(f), I hereby proclaim that the immigrant and nonimmigrant entry into the United States of aliens from countries referred to in section 217(a)(12) of the INA, 8 U.S.C. 1187(a)(12), would be detrimental to the interests of the United States, and I hereby suspend entry into the United States, as immigrants and nonimmigrants, of such persons for 90 days from the date of this order (excluding those foreign nationals traveling on diplomatic visas, North Atlantic Treaty Organization visas, C-2 visas for travel to the United Nations, and G-1, G-2, G-3, and G-4 visas).

The following day, a DHS spokesperson emailed a journalist that the order would bar green card holders (i.e., legal permanent residents or LPRs; the residency cards haven't been green for decades), which of course set off a panic with all the LPRs who rightfully thought they were done dealing with immigration roadblocks. So the following day, DHS said that it was in the national interest to use the flexibility of the order to not bar LPRs. What did DHS miss in all this? The definitions section of the INA specifically exempts LPRs from needing "admission" (which includes "entry" authorized by an immigration officer) under the immigration laws unless they've done something to lose their LPR status. Here's the relevant statute:

  INA Section 101(13)     (A) The terms "admission" and "admitted" mean, with respect to an alien, the lawful entry of the alien into the United States after inspection and authorization by an immigration officer.          (C) An alien lawfully admitted for permanent residence in the United States shall not be regarded as seeking an admission into the United States for purposes of the immigration laws unless the alien-[and then there is a short list of things saying what an LPR can have done to lose LPR status, which is primarily commit a crime or overstay outside the USA].  

An LPR is considered already "admitted for permanent residence." They don't have to "enter" the USA under the umbrella of the immigration laws. Which makes sense because they already immigrated. Immigrate is a verb meaning to move to a place to settle down, and once you've done it, you don't have to do it again, so no more messing around with immigrant petitions, immigrant visas, or immigrant admission. LPRs are simply coming home when they return back to the USA after a short stay abroad. Hence the executive order doesn't do anything to bar LPRs because they require no "immigration benefits" to reenter the USA once inspection reveals that they are indeed LPRs who remain in status.

Why am I talking about all this now? Because no one, from DHS to the White House counsel to the DOJ to the Ninth Circuit Court of Apppeals seems to have caught this point of law. Yesterday's ruling from the Ninth Circuit openly and clearly makes this mistake, as seen on page 20 of its ruling:

In the district court, the States argued that the Executive Order violates the procedural due process rights of various aliens in at least three independent ways. First, section 3(c) denies re-entry to certain lawful permanent residents and non-immigrant visaholders without constitutionally sufficient notice and an opportunity to respond. Second, section 3(c) prohibits certain lawful permanent residents and non-immigrant visaholders from exercising their separate and independent constitutionally protected liberty interests in travelling abroad and thereafter re-entering the United States. 

Do you see what the Ninth Circuit did there? They interpreted "immigrants" from the executive order to mean LPRs. This is a dumb mistake showing that of all the lawyers involved no one, even at the penultimately-supreme court level, has looked at INA Section 101 and realized that LPRs aren't treated by the law "as immigrants" when it comes to entering the USA. Any DHS agent working a port of entry knows that LPRs aren't the same thing as someone entering the USA with an immigrant visa in hand; the first category already did immigration paperwork in the past (huge hassle that it all was for them) at the border and/or in the USA, while the second is currently immigrating and has to be "processed" as an "immigrant" in "secondary." The executive order couldn't deny immigration benefits to LPRs entering the USA because they don't need immigration benefits to enter.

I know the INA is tricky, but this mistake should never happened. Every lawyer in the executive branch and courts who let this through should be embarrassed that they didn't check the INA definitions.

Another one out the door

I just submitted another medical hypothesis to the journal Medical Hypotheses this week. I put a lot of hours into it, and it's nice to be getting back into normal life now. I'll post a summary of the hypothesis after it is published.

Yesterday I turned in a pre-enrollment packet for child #4, who will be starting kindergarten in August. That is the same child who gave herself a haircut last month. It's hard to believe she'll be sitting quietly in a classroom and being a "pupil" six months from now. And I'll probably only believe it when I see it! She's a handful.