A toxicological assessment of spermidine trihydrochloride produced using an engineered strain of Saccharomyces cerevisiae.

Spermidine is a polyamine consumed in the diet, endogenously biosynthesized in most cells, and produced by the intestinal microbiome. A variety of foods contribute to intake of spermidine along with other polyamines. Spermidine trihydrochloride (spermidine-3HCl) of high purity can be produced using an engineered strain of Saccharomyces cerevisiae. Spermidine has a demonstrated history of safe use in the diet; however, limited information is available in the public literature to assess the potential toxicity of spermidine-3HCl. To support a safety assessment for this spermidine-3HCl as a dietary source of spermidine, authoritative guideline and good laboratory practice (GLP) compliant in vitro genotoxicity assays (bacterial reverse mutation and mammalian micronucleus assays) and a 90-day oral (dietary) toxicity study in rats were conducted with spermidine-3HCl. Spermidine-3HCl was non-genotoxic in the in vitro assays, and no adverse effects were reported in the 90-day oral toxicity study up to the highest dose tested, 12500 ppm, equivalent to 728 mg/kg bw/day for males and 829 mg/kg bw/day for females. The subchronic no observed adverse effect level (NOAEL) is 728 mg/kg bw/day.

A randomized controlled study of a consent intervention for participating in an NIH genome sequencing study.

To make an informed choice to participate in a genome sequencing study that may yield primary and secondary findings, one understands relevant information in the context of personal values. Consent forms to enroll in a sequencing study can be long and complex. The efficacy of the professional encounter to consider the information contained in the consent form and make an informed choice is unknown. Women diagnosed with primary ovarian insufficiency and eligible for a sequencing study were randomized to participate in one of two encounters with a genetic counselor: a consent intervention using a lower literacy, less dense form or a standard consent encounter. Data were complete for 188 of 225 participants. The average time was 32 min for the intervention and 34 min for the standard, with the intervention encounter generating more questions from participants. At six weeks following consent, no differences were found between the two groups in primary outcomes: 'sequencing benefits' knowledge (d = 0.12, 95%CI: -0.03,0.27), 'sequencing limitations' knowledge (d = 0.04, 95%CI: -0.13,0.21), expected personal benefits (d = -0.01, 95%CI: -0.26,0.23), and decisional conflict (d = 0.04, 95%CI: -0.14,0.21). Although intentions to learn secondary variants were high, only 60% (113) of participants made an informed choice as defined by the multi-dimensional model of informed choice. We found that a modified consent intervention was as effective as a standard encounter and led to more interaction. Our data suggest that making decisions to receive secondary findings may be particularly challenging and in need of further investigation to achieve informed choice.