Real-World Evidence to Reinforce Clinical Trial Evidence in Health Technology Assessment: A Critical Review of Real-World Evidence Requirements from Seven Countries and Recommendations to Improve Acceptance.

Background: Real-world evidence (RWE) can reinforce clinical trial evidence in health technology assessment (HTA).

Objectives: Review HTA bodies' (HTAbs) requirements for RWE, real uses, and acceptance across seven countries (Brazil, Canada, France, Germany, Italy, Spain, and the United Kingdom) and outline recommendations that may improve acceptance of RWE in efficacy/effectiveness assessments and appraisals processes.

Methods: RWE requirements were summarized based on HTAbs' guidelines.

Glycolate combats massive oxidative stress by restoring redox potential in Caenorhabditis elegans.

Upon exposure to excessive reactive oxygen species (ROS), organismal survival depends on the strength of the endogenous antioxidant defense barriers that prevent mitochondrial and cellular deterioration. Previously, we showed that glycolic acid can restore the mitochondrial membrane potential of C. elegans treated with paraquat, an oxidant that produces superoxide and other ROS species, including hydrogen peroxide.

Functional Exchangeability of Oxidase and Dehydrogenase Reactions in the Biosynthesis of Hydroxyphenylglycine, a Nonribosomal Peptide Building Block.

A key problem in the engineering of pathways for the production of pharmaceutical compounds is the limited diversity of biosynthetic enzymes, which restricts the attainability of suitable traits such as less harmful byproducts, enhanced expression features, or different cofactor requirements. A promising synthetic biology approach is to redesign the biosynthetic pathway by replacing the native enzymes by heterologous proteins from unrelated pathways. In this study, we applied this method to effectively re-engineer the biosynthesis of hydroxyphenylglycine (HPG), a building block for the calcium-dependent antibiotic of Streptomyces coelicolor, a nonribosomal peptide.

Vectorial signalling mechanism required for cell-cell communication during sporulation in Bacillus subtilis.

Spore formation in Bacillus subtilis takes place in a sporangium consisting of two chambers, the forespore and the mother cell, which are linked by pathways of cell-cell communication. One pathway, which couples the proteolytic activation of the mother cell transcription factor σ(E) to the action of a forespore synthesized signal molecule, SpoIIR, has remained enigmatic. Signalling by SpoIIR requires the protein to be exported to the intermembrane space between forespore and mother cell, where it will interact with and activate the integral membrane protease SpoIIGA.

Influence of high concentration monovalent cations on the protein partitioning in polyethyleneglycol 1500-phosphate aqueous two-phase systems.

The influence of chloride salts of Na+, Rb+ and Cs+ at concentrations from 0.15 to 1.2M was studied with bovine albumin, trypsin, ovoalbumin and lysozyme partitioning in an aqueous two-phase system formed by polyethyleneglycol 1500 and potassium phosphate at pH 7.