Recombinant cell bioassays for the detection of (gluco)corticosteroids and endocrine-disrupting potencies of several environmental PCB contaminants

Sensitive and robust bioassays for glucocorticoids are very useful for the pharmaceutical industry, environmental scientists and veterinary control. Here, a recombinant yeast cell was constructed that expresses the human glucocorticoid receptor alpha and a green fluorescent reporter protein in response to glucocorticoids. Both the receptor construct and the reporter construct were stably integrated into the yeast genome. The correct and specific functioning of this yeast glucocorticoid bioassay was studied by exposures to cortisol and other related compounds and critically compared to a GR-CALUX bioassay based on a human bone cell. Although less sensitive, the new yeast glucocorticoid bioassay showed sensitivity towards all (gluco)corticoids tested, with the following order in relative potencies: budesonide >> corticosterone > dexamethasone > cortisol = betamethasone > prednisolone > aldosterone. Hormone representatives for other hormone nuclear receptors, like 17β-estradiol for the oestrogen receptor, 5α-dihydrotestosterone for the androgen receptor and progesterone for the progesterone receptor, showed no clear agonistic responses, whilst some polychlorinated biphenyls were clearly able to interfere with the GR activity

Specific guidelines for assessing and improving the methodological quality of economic evaluations of newborn screening.

Background: Economic evaluation of newborn screening poses specific methodological challenges. Amongst others, these challenges refer to the use of quality adjusted life years (QALYs) in newborns, and which costs and outcomes need to be considered in a full evaluation of newborn screening programmes. Because of the increasing scale and scope of such programmes, a better understanding of the methods of high-quality economic evaluations may be crucial for both producers/authors and consumers/reviewers of newborn screening-related economic evaluations. The aim of this study was therefore to develop specific guidelines designed to assess and improve the methodological quality of economic evaluations in newborn screening. Methods: To develop the guidelines, existing guidelines for assessing the quality of economic evaluations were identified through a literature search, and were reviewed and consolidated using a deductive iterative approach. In a subsequent test phase, these guidelines were applied to various economic evaluations which acted as case studies. Results: The guidelines for assessing and improving the methodological quality of economic evaluations in newborn screening are organized into 11 categories: "bibliographic details", "study question and design", "modelling", "health outcomes", "costs", "discounting", "presentation of results", "sensitivity analyses", "discussion", "conclusions", and "commentary". Conclusions: The application of the guidelines highlights important issues regarding newborn screening-related economic evaluations, and underscores the need for such issues to be afforded greater consideration in future economic evaluations. The variety in methodological quality detected by this study reveals the need for specific guidelines on the appropriate methods for conducting sound economic evaluations in newborn screening