Late stent thrombosis has not been reported in the absence of prior coronary brachytherapy. We reviewed our experience in 1,855 consecutive patients who received at least one stent and did not receive coronary brachytherapy. Half of all stent thromboses occurred within the first week and nearly 65% (22) occurred within 15 days. The incidence of stent thrombosis within this traditional time frame was 1.2%. An additional 12 patients, however, presented with stent thrombosis between 33 and 270 days post-procedure (mean ‫؍‬ 72.9 ؎ 23 days). The true incidence of stent thrombosis was therefore 1.8% (34/1,855). There were three bypass operations, one stroke and two deaths in the late stent thrombosis group. Late stent thrombosis is an unusual but serious complication in patients who have not received coronary brachytherapy. Intracoronary radiation may potentiate a phenomenon that already occurs after stent deployment. Prolonged treatment (6 -12 months) with anti-platelet agents should be considered after percutaneous intervention with coronary stents. Cathet Cardiovasc Intervent 2001;53:23-28.

Antibiotic resistant bacteria are an emerging global health threat. New antimicrobials are urgently needed. The injectisome type III secretion system (T3SS), required by dozens of Gram-negative bacteria for virulence but largely absent from non-pathogenic bacteria, is an attractive antimicrobial target. We previously identified synthetic cyclic peptomers, inspired by the natural product phepropeptin D, that inhibit protein secretion through the Yersinia Ysc and Pseudomonas aeruginosa Psc T3SSs, but do not inhibit bacterial growth. Here we describe identification of an isomer, 4EpDN, that is two-fold more potent (IC50 of 4 μM) than its parental compound. Furthermore, 4EpDN inhibited the Yersinia Ysa and the Salmonella SPI-1 T3SSs, suggesting that this cyclic peptomer has broad efficacy against evolutionarily distant injectisome T3SSs. Indeed, 4EpDN strongly inhibited intracellular growth of Chlamydia trachomatis in HeLa cells, which requires the T3SS. 4EpDN did not inhibit the unrelated Twin arginine translocation (Tat) system, nor did it impact T3SS gene transcription. Moreover, although the injectisome and flagellar T3SSs are evolutionarily and structurally related, the 4EpDN cyclic peptomer did not inhibit secretion of substrates through the Salmonella flagellar T3SS, indicating that cyclic peptomers broadly but specifically target the injestisome T3SS. 4EpDN reduced the number of T3SS needles detected on the surface of Y. pseudotuberculosis as detected by microscopy. Collectively, these data suggest that cyclic peptomers specifically inhibit the injectisome T3SS from a variety of Gram-negative bacteria, possibly by preventing complete T3SS assembly.

Late stent thrombosis has not been reported in the absence of prior coronary brachytherapy. We reviewed our experience in 1,855 consecutive patients who received at least one stent and did not receive coronary brachytherapy. Half of all stent thromboses occurred within the first week and nearly 65% (22) occurred within 15 days. The incidence of stent thrombosis within this traditional time frame was 1.2%. An additional 12 patients, however, presented with stent thrombosis between 33 and 270 days post-procedure (mean = 72.9 +/- 23 days). The true incidence of stent thrombosis was therefore 1.8% (34/1,855). There were three bypass operations, one stroke and two deaths in the late stent thrombosis group. Late stent thrombosis is an unusual but serious complication in patients who have not received coronary brachytherapy. Intracoronary radiation may potentiate a phenomenon that already occurs after stent deployment. Prolonged treatment (6-12 months) with anti-platelet agents should be considered after percutaneous intervention with coronary stents.

Wolbachia, a vertically transmitted endosymbiont infecting many insects, spreads rapidly through uninfected populations by a mechanism known as cytoplasmic incompatibility (CI). In CI, a paternally delivered modification of the sperm leads to chromatin defects and lethality during and after the first mitosis of embryonic development in multiple species. However, whether CI-induced defects in later stage embryos are a consequence of the first division errors or caused by independent defects remains unresolved. To address this question, we focused on ~1/3 of embryos from CI crosses in Drosophila simulans that develop apparently normally through the first and subsequent pre-blastoderm divisions before exhibiting mitotic errors during the mid-blastula transition and gastrulation. We performed single embryo PCR and whole genome sequencing to find a large percentage of these developed CI-derived embryos bypass the first division defect. Using fluorescence in situ hybridization, we find increased chromosome segregation errors in gastrulating CI-derived embryos that had avoided the first division defect. Thus, Wolbachia action in the sperm induces developmentally deferred defects that are not a consequence of the first division errors. Like the immediate defect, the delayed defect is rescued through crosses to infected females. These studies inform current models on the molecular and cellular basis of CI.

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