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1.
EClinicalMedicine ; 62: 102125, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37593222

RESUMO

Background: Young people are at high risk of sexually transmitted infections (STIs). We report STI testing uptake, prevalence and incidence within a community-based integrated HIV and sexual and reproductive health service for youth, being evaluated in a cluster randomised trial in Zimbabwe. Methods: This paper reports the intervention findings of the cluster randomised trial whereby STI testing was offered to all service attendees (16-24 years) in 12 intervention clusters over 12 months between October 5, 2020, and December 17, 2021, in Zimbabwe. Testing for Chlamydia trachomatis [CT] and Neisseria gonorrhoeae [NG] was offered to males and females with results available in one week and follow-up of test-positive clients by telephone. Trichomonas vaginalis [TV] testing was offered to females only with same day results and treatment. Youth testing positive for any STI were offered partner notification slips and free treatment for partners. This trial was registered with ISRCTN Registry, ISRCTN15013425. Findings: Overall, 8549/9891 (86.1%) eligible youth accepted CT/NG testing. Prevalence of CT and NG was 14.7% (95% CI 13.6-15.8) and 2.8% (95% CI 2.2-3.6) respectively. Combined prevalence of CT, NG or TV in women was 23.2% (95% CI 21.5-25.0). After adjusting for cluster, age and sex, the odds of NG were increased in those living with HIV (aOR 3.14, 95% CI 2.21-4.47). The incidence rate among those who initially tested negative for CT or NG was 25.6/100PY (95% CI 20.6-31.8). CT/NG treatment uptake was 924/1526 (60.6%). TV treatment uptake was 483/489 (98.8%). A partner returned for treatment for 103/1807 clients (5.7%). Interpretation: Our findings show high acceptability of STI testing among youth. STI prevalence was high particularly among females and youth with HIV, underscoring the need for integration of HIV and STI services. Funding: MRC/ESRC/DFID/NIHR (MR/T040327/1) and Wellcome Trust (206316/Z/17/Z).

2.
ACS Med Chem Lett ; 6(2): 221-4, 2015 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-25699153

RESUMO

The integrin αvß6 is a potential target for treatment of idiopathic pulmonary fibrosis (IPF). Equilibrium dialysis (ED) was investigated for its ability to report ligand binding in an αvß6 inhibitor screening assay. As a preliminary experiment, an established peptidomimetic inhibitor of the integrin was dialyzed against αvß6, and the fraction bound (f b) and percentage saturation determined by liquid chromatography-mass spectrometry (LC-MS) analysis. Quantitation of the inhibitor in the two chambers of the ED cartridge revealed an uneven distribution in the presence of αvß6, corresponding to near saturation binding to the protein (93 ± 3%), while the control (without integrin) showed an equal partitioning of the inhibitor on either side of the dialysis membrane. A competitive ED assay with a 12 component mixture of antagonists was conducted, and the results compared with an established cell adhesion assay for quantifying αvß6 inhibition of individual antagonists. Compounds clustered into three groupings: those with pIC 50 values between ca. 5.0 and 5.5, which possessed ED f b values indistinguishable from the controls, those with pIC 50s of 6.5 ± 0.2, which exhibited detectable integrin binding (f b 13-25%) in the ED assay, and a single compound of pIC 50 7.2 possessing an f b value of 38%. A good correlation between ED-derived f b and pIC 50 was observed despite the two assays utilizing quite different outputs. These results demonstrate that ED with LC-MS detection shows promise as a rapid αvß6 integrin antagonist screening assay for mixtures of putative ligands.

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