Disease: Von-willebrand Disorder Type 3

Patient: 26 yo, female

Variant: VWF NM_000552.5 c:997+118 T>G g.(6073501 A>C), homozygous, intronic

Phenotypes: No detectable VWF in plasma, early onset bleeding complications, epistaxis, easy bruising, bleeding following injury, menorrhagia, iron-deficient anemia

Note: underwent prophylaxis replacement therapy, on-demand antihemorrhagic treatments, oral contraceptives, and replacement therapy.

Family: not mentioned

Predictions:

VEP SpliceAI tool predicted variant likely deleterious (delta score 0.95)

Used Polyphen-2 and SIFT which determined pathogenic likelihood.

Neural Network Splicing, Alternative Splice Site Predictor, plug-in MaxEnt(For 5' donor site) of Human Splicing Finder all concur this variant can create a new donor splice site in intron 8. Contains premature stop codon and susceptible to NMD.

Functional work:

qRT-PCR performed to identify levels of VWF in IP-derived endothelial cells.

histochemical immunostaining for IP-derived endothelial cells confirm no VWF production, only a residual amount present. Suggests leaky mutation.

performed RNA sequencing to assess co-regulated gene networks

solve consitency issues

—Proverbs 16:31

Naturally as someone who went gray prematurely, I'm in total agreement with this! 😁

Vaccination among the pregnant lagging despite growing evidence of safety and efficacy. (2021, December 10). Healthy Debate. https://healthydebate.ca/2021/12/topic/vaccination-pregnant-safe-efficacy/

ReconfigBehSci. (2021, November 23). query: Https://unherd.com/2021/11/the-lefts-covid-failure/ “Is there really no progressive criticism to be made about the quarantining of healthy individuals, when the latest research suggests there is a vanishingly small difference in terms of transmission between the vaccinated and the unvaccinated?” 1/2 [Tweet]. @SciBeh. https://twitter.com/SciBeh/status/1463146737804140558

Arolas, H. P. i, Acosta, E., Casasnovas, G. L., Lo, A., Nicodemo, C., Riffe, T., & Myrskylä, M. (2020). Global years of life lost to COVID-19 [Preprint]. SocArXiv. https://doi.org/10.31235/osf.io/gveaj

War is not only difficult on the physical aspect of an individual; it is just as difficult on the emotional and mental capacity of a human. It is factual that WWI culminated an astronomical amount of casualties, destruction, and disablement. This reference to being “drunk” may help guide us into the notion that soldiers are not able to differentiate between fantasy and reality under the duress of mentioned “fatigue.” We can understand that the state of "drunk" alters your reality and can have dangerous repercussions; in this sense, the loss of one's mind or life. In the prior lines we have loss of physical functionalities of the human body with words such as “limped on,” “lame,” and “blind,” which coincides with the premature aging or physical deterioration of the soldiers.

With the introduction and evolution of chemical weapons used in this war (WWI); human bodies were no match for the damage these weapons were designed to inflict. Leading into the imagery of soldiers physically deteriorating when using phrases such as "bent double," "coughing like hags," and "men marched asleep;" would not lead one to believe that war is “sweet and fitting” in any capacity. With the use of the word “beggars” our minds may envision the effects of poverty and desperation which war seems to produce, and in this sense, we are given language expressing the overwhelming misery and accelerated age progression with the use of “old.” These descriptions challenge the assumptions the mind tends to gravitate towards when picturing what it means to "die for ones country."

The younger generation rises while the old one falls. The new generation of rulers are going to have to re-figure out how to function and run a kingdom properly. They are all too young to understand the wisdom that comes from a King and his rule. King Lear was foolish to believe his daughters ready for inheritance.