Wheel Replacing Pyramid: Better Paradigm Representing Totality of Evidence-Based Medicine.

Background: Evidence-based medicine (EBM), as originally conceived, used all types of peer-reviewed evidence to guide medical practice and decision-making. During the SARS-CoV-2 Coronavirus disease (COVID-19) pandemic, the standard usage of EBM, modeled by the Evidence-Based Medicine Pyramid, undermined EBM by incorrectly using pyramid levels to assign relative quality. The resulting pyramid-based thinking is biased against reports both in levels beneath randomized control trials (RCTs) and those omitted from the pyramid entirely.

How Does Severe Acute Respiratory Syndrome-Coronavirus-2 Affect the Brain and Its Implications for the Vaccines Currently in Use.

This mini-review focuses on the mechanisms of how severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) affects the brain, with an emphasis on the role of the spike protein in patients with neurological symptoms. Following infection, patients with a history of neurological complications may be at a higher risk of developing long-term neurological conditions associated with the α-synuclein prion, such as Parkinson's disease and Lewy body dementia. Compelling evidence has been published to indicate that the spike protein, which is derived from SARS-CoV-2 and generated from the vaccines currently being employed, is not only able to cross the blood-brain barrier but may cause inflammation and/or blood clots in the brain.

Bioanalysis of siRNA and oligonucleotide therapeutics in biological fluids and tissues.

This article summarizes bioanalytical avenues for the determination of siRNA and oligonucleotide therapeutics, with an emphasis on hybridization methods. Aspects of the chemistry and delivery of investigational oligonucleotide therapeutics are considered. The nature of the oligonucleotide under investigation will dictate the best analytical course of action; each method has its advantages and disadvantages, depending upon the oligonucleotide test article and the anticipated toxicokinetic and pharmacokinetic study parameters.