https://academic.oup.com/eurheartj/article-lookup/doi/10.1093/eurheartj/ehx260
What do people make of this?
βAmerican physicians are now treating dyslipidemia according to a fifth iteration of national guidelines for the use of lipid-lowering therapies [1]. These guidelines are developed with considerable care and deliberation and are, by design, as evidence-based as possible. Specific recommendations are made in order to safely and optimally use pharmacologic interventions to maximize clinical benefit. Since publication of the first Adult Treatment Panel for the Management of Blood Cholesterol, over three decades have elapsed. The association of serum low-density lipoprotein cholesterol (LDL-C) with atherosclerotic cardiovascular disease is one of the most extensively studied and highly established issues in all of medicine [2].
There is unequivocal evidence that the use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) significantly reduce ASCVD events (myocardial infarction [MI], stroke, need for revascularization, and mortality) in both primary and secondary prevention settings [3,4]. Moreover, statin therapy is just as beneficial in the elderly with established vascular disease as it is in younger groups of patients [5]. Higher dose statin therapy with greater LDL-C reduction provides additional ASCVD event rate reduction compared to lower dose statin therapy [6]. Other LDL-C lowering agents such as ezetimibe [7] and the proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies [8,9] provide incremental risk reduction when used as adjuvant therapies to background statin use in high risk patients. Despite the great specificity and clarity of guidelines both in the US and in other regions of the world, the appropriate use of lipid-lowering therapies (LLT) is disappointingly and frustratingly low. Given the incontrovertible strength of evidence, why has this become such a perennial, lasting observation?
β¦ Perhaps it is time to change the view of LDL-C. LDL-C is the end product of lipoprotein metabolism. Its precursors, very low-density lipoprotein and interediate density lipoprotein, are reservoirs of oxidizable substrate (triglycerides, fatty acids). LDL is highly concentrated with cholesterol. The histologic components of arterial walls cannot catabolize cholesterol. The assumption is that LDL distributes this cholesterol as a vital regulator of cell membrane fluidity or is an important donor of cholesterol to steroidogenic tissues. All somatic cells have the capacity to produce their own cholesterol. When
... keep reading on reddit β‘https://doi.org/10.1093/eurheartj/ehaa868
https://pubmed.ncbi.nlm.nih.gov/33326580
Abstract
Hypercholesterolaemia is an important risk factor for cardiovascular disease. Both total and LDL cholesterol levels are three-fold higher at the end of the first year of life and about four-fold higher in adulthood compared with the neonatal period. In the USA, only 25% of infants are exclusively breastfed and simple carbohydrate-rich formulas are preferentially consumed. Spikes in fasting glucose and insulin have been reported in formula-fed infants and are associated with higher levels of proprotein convertase subtilisin/kexin type 9, suggesting a potential link between high simple sugar intake and consequent increase in LDL cholesterol in early childhood.
------------------------------------------ Info ------------------------------------------
Open Access: False
Authors:
Reading a just published discussion about some very recent studies, when they ask themselves why this virus is spreading so fast in comparison to, for example, the first SARS (and many others), they have come to the conclusion that it may be related to a very special particularity found in this pathogen.
>Nature, 6 March 2020, News >Why does the coronavirus spread so easily between people?
In its surface, it has a spike protein that interacts with cellular receptors, as many others have, but in this case, it holds in that protein a special zone that reacts with an enzyme that humans have in the lungs, liver and small intestine, called Furin (maybe that's why is capable of destroying liver tissue).
It seems that the reaction between our own enzyme and the viral spike renders it much more aggressive (more capable of entering inside the cell) and this characteristic can be used to try to stop it.
The mentioned interaction isn't often seen in other common viral pathogens, except in severe strains of the influenza virus but in another part of it. Its cousin, the first SARS doesn't have it.
It's an old enemy that we have tried to address years ago because the Anthrax toxin also needs this Furin enzyme to be activated.
So far, the search for a molecule that could block this Furin enzyme hasn't been of much success.
The most potent compound is phenylacetyl-Arg-Val-Arg-4-amidinobenzylamide, which availability I am unaware of. The usable candidates list is scarce, most of them being large proteins that would need genetically modified bacteria to produce it (a long and expensive process), except for the only one readily accessible, the andrographolide family of molecules derived from de plant Andrographis Paniculata, which may be very useful either for weakening the virus by themselves or leading to the creation of new compounds.
Read: >Synthetic small molecule furin inhibitors derived from 2,5-dideoxystreptamine
Another substance is mentioned in the researches, called Agmatine (a chemical substance which is naturally created from the amino acid arginine), that seems to block Furin, but not with the same strength.
There are also some metallic compounds which have Zinc and Copper in their structure that have some Furin blocking abilities.
>[Potent inhi
... keep reading on reddit β‘I've decided to write this post to try to be of some help to whoever may need to protect himself from this new virus or to ease it if you've already caught it and you cannot afford conventional healthcare, or you want to complement it (or you just aren't covered by any insurance). Nothing here might be considered to be a cure, but, even so, there's science behind it and studies, some of them just published a few days ago, and some others were investigated in the past SARS and MERS outbreaks and can be applicable now because of similarities between them.
In cases like this, it's usual to re-investigate some drugs that have been proven successful in treating similar viruses and reutilize them for the newly discovered one, because they often share common targets that can be addressed. If this process fails to find a good candidate, a research is done using previously known substances, that can be thousands, both natural and man-made, to look for the more promising ones and, then, try them, first in vitro and later in animals and humans.
The trial with some old pharmaceutical antivirals hasn't been particularly exciting, the flu ones have failed to work (like Oseltamivir), but some designed for an Ebola trial and for the first SARS seem to work well, like Remdesivir. The problem is that they either aren't yet available or that they'll be prohibitively expensive in some countries.
The good news is that some natural (or natural derived) ones have been especially effective, with Chloroquine being the big winner of the round. Chloroquine is derived from the Cinchona tree, and has been used to treat malaria, autoimmune conditions... It's very difficult to compare the usefulness of two drugs being so early, but, at this time, it's at the same level as antivirals and it has been tried in at least 280 persons, obtaining very good results.
One key matter regarding this substance is that it seems that the new Covid-19 kills many people by something called Cytokine Storm, that's basically an hyper-reaction of the immune system that makes you collapse in a similar way that an anaphylactic reaction does. This is where the Cholorquine comes in, changing the way that some cellular organelles, called lysosomes, work, keeping them from doing such widespread damage. Apart from it, the substance has good antiviral effects on its own.
Beware that Chloroquine is a powerful substance with many contraindications and interactions, some of them can be fatal, so, even if
... keep reading on reddit β‘Han E, Cho NH, Moon SS, Cho H. Comparison of Serum PCSK9 Levels in Subjects with Normoglycemia, Impaired Fasting Glucose, and Impaired Glucose Tolerance. Endocrinol Metab (Seoul). 2020;35(2):480-483. doi:10.3803/EnM.2020.35.2.480
https://doi.org/10.3803/enm.2020.35.2.480
Abstract
We investigated proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations in individuals with normoglycemia, impaired fasting glucose (IFG), and impaired glucose tolerance (IGT). This was a pilot, cross-sectional study including 92 individuals who had not been diagnosed with or treated for diabetes. We measured PCSK9 levels in three groups of subjects; namely, normoglycemia (n=57), IFG (n=21), and IGT (n=14). Individuals with IFG and IGT showed higher PCSK9 concentrations than those in the normoglycemic group, with the highest serum PCSK9 concentrations found in individuals with IGT (55.25Β±15.29 ng/mL for normoglycemia, 63.47Β±17.78 ng/mL for IFG, 72.22Β±15.46 ng/mL for IGT, analysis of variance P=0.001). There were no significant differences in high- or low-density lipoprotein cholesterol among groups. Serum PCSK9 levels are increased in patients with prediabetes compared to subjects with normoglycemia.
http://www.e-enm.org/upload/pdf/EnM-2020-35-2-480.pdf
>A mutation in the gene encoding proprotein convertase subtilisin/kexin type 9 (PCSK9) was recently discovered in subjects with familial hypercholesterolemia*. ... Mendelian randomization studies show that PCSK9 genetic variants are associated with* higher fasting blood glucose in patients with type 2 diabetes (T2D) or impaired fasting glucose (IFG), indicating a risk of hyperglycemia for patients using PCSK9 inhibitor drugs [3].
Phil
Go post NSFW jokes somewhere else. If I can't tell my kids this joke, then it is not a DAD JOKE.
If you feel it's appropriate to share NSFW jokes with your kids, that's on you. But a real, true dad joke should work for anyone's kid.
Mods... If you exist... Please, stop this madness. Rule #6 should simply not allow NSFW or (wtf) NSFL tags. Also, remember that MINORS browse this subreddit too? Why put that in rule #6, then allow NSFW???
Please consider changing rule #6. I love this sub, but the recent influx of NSFW tagged posts that get all the upvotes, just seem wrong when there are good solid DAD jokes being overlooked because of them.
Thank you,
A Dad.
Well, toucan play at that game.
Martin Freeman, and Andy Serkis.
They also play roles in Lord of the Rings.
I guess that makes them the Tolkien white guys.
She said apple-lutely
'Eye-do'
This is my first post pls don't kill me lol.
The people in the comment section is why I love this subreddit!!
Cred once again my sis wants credit lol
I heard parents named their children lance a lot.
First post please don't kill me
Edit: i went to sleep and now my inbox is dead, thank you kind strangers for the awards!
Japan.
second hand stores!
it's Hans free now..
Old Neeeeiiiiighvy
10+10 is twenty and 11+11 is twenty too
Keep in mind, my son is 4 years old, so everything is an original to him.
I had to work late into the evening yesterday, and he was just going to bed when I got home. I had left home for the office nearly 14 hours prior, had a long day, lots of meetings, traffic, etc.
When I walked through the door, I was exhausted, run down, and starving. My wife hugged me and asked how my day was, and I replied, "Done. It was a good day, but has got me exhausted. I just want to grab a bite and go to bed. I'm hungry."
From my son's bedroom, I hear him shout, "Hi Hungry! Nice to meet you!"
Not only did it make me laugh, but I completely forgot about how hungry and tired I was. I went to his bedroom, and we laughed together about it. It was exactly what I needed.
Edit: Thanks for all the awards, kind strangers! I'll let my son know y'all enjoyed his joke too!
A buck-an-ear!
I Thank ye kind Matey for the booty! I be truly overwhelmed! Thank you!
Holy cow! Thank you everyone for the upvotes and awards! I wasnβt expecting this!
He should have a good vowel movement. His next diaper change could spell disaster though.
That was the punchline
Making it all the way home and realizing that they forgot one of the containers:
Riceless
I've decided to write this post to try to be of some help to whoever may need to protect himself from this new virus or to ease it if you've already caught it and you cannot afford conventional healthcare, or you want to complement it (or you just aren't covered by any insurance). Nothing here might be considered to be a cure, but, even so, there's science behind it and studies, some of them just published a few days ago, and some others were investigated in the past SARS and MERS outbreaks and can be applicable now because of similarities between them.
In cases like this, it's usual to re-investigate some drugs that have been proven successful in treating similar viruses and reutilize them for the newly discovered one, because they often share common targets that can be addressed. If this process fails to find a good candidate, a research is done using previously known substances, that can be thousands, both natural and man-made, to look for the more promising ones and, then, try them, first in vitro and later in animals and humans.
The trial with some old pharmaceutical antivirals hasn't been particularly exciting, the flu ones have failed to work (like Oseltamivir), but some designed for an Ebola trial and for the first SARS seem to work well, like Remdesivir. The problem is that they either aren't yet available or that they'll be prohibitively expensive in some countries.
The good news is that some natural (or natural derived) ones have been especially effective, with Chloroquine being the big winner of the round. Chloroquine is derived from the Cinchona tree, and has been used to treat malaria, autoimmune conditions... It's very difficult to compare the usefulness of two drugs being so early, but, at this time, it's at the same level as antivirals and it has been tried in at least 280 persons, obtaining very good results.
One key matter regarding this substance is that it seems that the new Covid-19 kills many people by something called Cytokine Storm, that's basically an hyper-reaction of the immune system that makes you collapse in a similar way that an anaphylactic reaction does. This is where the Cholorquine comes in, changing the way that some cellular organelles, called lysosomes, work, keeping them from doing such widespread damage. Apart from it, the substance has good antiviral effects on its own.
Beware that Chloroquine is a powerful substance with many contraindications and interactions, some of them can be fatal, so, even if
... keep reading on reddit β‘