The recent discovery of Smac and the elucidation of its structure and function have led to the rapid development of Smac mimetics, comprising Smac derivative and mimicking molecules, for use in cancer treatment. Smac is an endogenous proapoptotic protein that resides in the mitochondria and is released when a cell is triggered to undergo programmed cell death. One of the mechanisms by which Smac promotes apoptosis is through its ability to inhibit inhibitors of apoptosis (IAPs), by direct inhibition and/or proteasomal degradation of some members of the IAP family, and therefore disinhibit caspases. Thus, the use of Smac mimetics as anticancer agents follows a rational approach in cancer therapeutics. This approach directly targets dysregulated, neoplastic cells that overexpress IAPs or underexpress Smac. Although Smac mimetics are able to elicit an anticancer response when used alone, these molecules can also function effectively and synergistically when combined with other therapeutic agents. A variety of Smac mimetic types comprising peptides, polynucleotides, and compounds have been studied both in vitro and in vivo. This discussion addresses the current status of Smac mimetics in cancer research.

Surveillance of circulating microbial populations is critical for monitoring the performance of a molecular diagnostic test. In this study, we characterized 31 isolates of Streptococcus agalactiae (group B Streptococcus [GBS]) from several geographic locations in the United States and Ireland that contain deletions in or adjacent to the region of the chromosome that encodes the hemolysin gene cfb, the region targeted by the Xpert GBS and GBS LB assays. PCR-negative, culturepositive isolates were recognized during verification studies of the Xpert GBS assay in 12 laboratories between 2012 and 2018. Whole-genome sequencing of 15 GBS isolates from 11 laboratories revealed four unique deletions of chromosomal DNA ranging from 181 bp to 49 kb. Prospective surveillance studies demonstrated that the prevalence of GBS isolates containing deletions in the convenience sample was Ͻ1% in three geographic locations but 7% in a fourth location. Among the 15 isolates with chromosomal deletions, multiple pulsed-field gel electrophoresis types were identified, one of which appears to be broadly dispersed across the United States.

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