Cofactors are intimately involved in steroid-regulated gene expression. Two critical questions are (1) the steps at which cofactors exert their biological activities and (2) the nature of that activity. Here we show that a new mathematical theory of steroid hormone action can be used to deduce the kinetic properties and reaction sequence position for the functioning of any two cofactors relative to a concentration limiting step (CLS) and to each other. The predictions of the theory, which can be applied using graphical methods similar to those of enzyme kinetics, are validated by obtaining internally consistent data for pair-wise analyses of three cofactors (TIF2, sSMRT, and NCoR) in U2OS cells. The analysis of TIF2 and sSMRT actions on GR-induction of an endogenous gene gave results identical to those with an exogenous reporter. Thus new tools to determine previously unobtainable information about the nature and position of cofactor action in any process displaying first-order Hill plot kinetics are now available.

Knee osteoarthritis (OA) treatment is challenging due to inefficacy and adverse effects of current medications. Probiotic treatment has been shown to promote bone metabolism, reduce pain and inflammatory responses of age-related musculoskeletal disorders, including OA. We aimed to investigate the effect of probiotic Lactobacillus casei Shirota (LcS) on patients with knee OA. 537 patients with knee OA were enrolled in this double-blind, placebo-controlled trial, who were randomised to receive skimmed milk containing either LcS or placebo daily for 6 months. Primary outcome was defined as changes in WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) and VAS (visual analog scale) scores. Secondary outcome was defined as changes in serum levels of high sensitivity C-reactive protein (hs-CRP). After 6 months of treatment, both WOMAC and VAS scores were significantly improved in the LcS groups of patients compared to the placebo group. Serum levels of hs-CRP were also significantly lower in patients receiving LcS than placebo. Strong linear correlations were observed between serum hs-CRP levels and WOMAC and VAS scores. LcS consumption could serve as a novel therapeutic option in the clinical management of knee OA, improving treatment outcome likely through reducing serum hs-CRP levels.

Virtual reality distraction can effectively relieve pain without side effects and is not reliant on a doctor's prescription. This tool is convenient for nurses to use, especially when analgesics are unavailable.

Background: Current descriptions of steroid hormone action are largely phenomenological rather than mechanistic. Results: Methodology is described for determining kinetically defined mechanisms and relative sites of action of any two cofactors with steroid receptors. Conclusion: Position and mode of reporter gene action are constant. Significance: Location and mechanistic action of cofactors, relative to each other and reporter, is assignable in sequence for receptor-regulated gene transactivation.