The first crystal structure of human cyclooxygenase-2, in the presence of a selective inhibitor, is similar to that of cyclooxygenase-1. The structure of the NSAID binding site is also well conserved, although there are differences in its overall size and shape which may be exploited for the further development of selective COX-2 inhibitors. A second COX-2 structure with a different bound inhibitor displays a new, open conformation at the bottom of the NSAID binding site, without significant changes in other regions of the COX-2 structure. These two COX-2 structures provide evidence for the flexible nature of cyclooxygenase, revealing details about how substrate and inhibitor may gain access to the cyclooxygenase active site from within the membrane.

No abstract

NAATs were performed on FCU, urethral, cervical, self-and clinician-collected VS. Sensitivity was compared to isolation using cervical and urethral swabs. Agreement of NAAT results between VS and cervical swabs or FCU was calculated. Specimens from 2,517 15-to 25-year-old asymptomatic women attending clinics at nine different centers were evaluated. Results with self-and clinician-collected VS were equivalent and were at least as good as results with FCU and cervical swabs. Across all sites, summary specificities for all specimens were >99%. Among culture-positive women, NAAT sensitivity with VS (93%) was as high as or higher than NAAT sensitivity with cervical swabs (91%) or FCU (80.6%) or culture of cervical swabs (83.5%). VS are appropriate specimens for diagnosing chlamydial genital tract infection by NAATs. That patients can efficiently collect them offers important benefits for screening programs. It would be beneficial for public health programs if the NAAT manufacturers sought FDA clearance for this specimen.

Aspergillus fumigatus is a filamentous fungus which can cause invasive disease in immunocompromised individuals. A. fumigatus can grow in medium containing up to 80% human serum, despite very low concentrations of free iron. The purpose of this study was to determine the mechanism by which A. fumigatus obtains iron from the serum iron-binding protein transferrin. In iron-depleted minimal essential medium (MEM), A. fumigatus growth was supported by the addition of holotransferrin (holoTf) or FeCl 3 but not by the addition of apotransferrin (apoTf). Proteolytic degradation of transferrin by A. fumigatus occurred in MEM-serum; however, transferrin degradation did not occur until late logarithmic phase. Moreover, transferrin was not degraded by A. fumigatus incubated in MEM-holoTf. Urea polyacrylamide gel electrophoresis showed that in MEM-holoTf, holoTf was completely converted to apoTf by A. fumigatus. In human serum, all of the monoferric transferrin was converted to apoTf within 8 h. Siderophores were secreted by A. fumigatus after 8 h of growth in MEM-serum and 12 h in MEM-holoTf. The involvement of small molecules in iron acquisition was confirmed by the fact that transferrin was deferrated by A. fumigatus even when physically separated by a 12-kDa-cutoff membrane. Five siderophores were purified from A. fumigatus culture medium, and the two major siderophores were identified as triacetylfusarinine C and ferricrocin. Both triacetylfusarinine C and ferricrocin removed iron from holoTf with an affinity comparable to that of ferrichrome. These data indicate that A. fumigatus survival in human serum in vitro involves siderophore-mediated removal of iron from transferrin. Proteolytic degradation of transferrin may play a secondary role in iron acquisition.

No abstract

Because of the rapid development of genital warts (GW) after infection, monitoring GW trends may provide early evidence of population-level human papillomavirus (HPV) vaccine effectiveness. Trends in GW diagnoses were assessed using public family planning administrative data. Between 2007 and 2010, among females younger than 21 years, these diagnoses decreased 35% from 0.94% to 0.61% (P(trend) < .001). Decreases were also observed among males younger than 21 years (19%); and among females and males ages 21-25 (10% and 11%, respectively). The diagnoses stabilized or increased among older age groups. HPV vaccine may be preventing GW among young people.

Treponemal immunoassays demonstrated excellent sensitivity for secondary, early latent, and seropositive primary syphilis. Sensitivity of FTA-ABS in primary syphilis was poor compared to the immunoassays and TP-PA. Given its high specificity and superior sensitivity, TP-PA is a better test to adjudicate discordant results with the reverse sequence algorithm than the FTA-ABS.

Chlamydia and gonorrhea prevalence was very high in females in all project sites. In males, chlamydia prevalence was high in some areas; however, gonorrhea prevalence was substantially lower. These prevalence data justify screening for chlamydia and gonorrhea among female adolescents in juvenile detention centers nationally.