We conducted a prospective study among women in Mombasa, Kenya, to determine whether Trichomonas vaginalis infection was associated with an increased risk of human immunodeficiency virus type 1 (HIV-1) infection. At monthly follow-up visits, laboratory screening for HIV-1 and genital tract infections was conducted. Among 1335 HIV-1-seronegative women monitored for a median of 566 days, there were 806 incident T. vaginalis infections (23.6/100 person-years), and 265 women seroconverted to HIV-1 (7.7/100 person-years). Trichomoniasis was associated with a 1.52-fold (95% confidence interval, 1.04-2.24-fold) increased risk of HIV-1 acquisition after adjustment for potential confounding factors. Treatment and prevention of T. vaginalis infection could reduce HIV-1 risk in women.
Hypochlorous acid (HOCl) is produced naturally by neutrophils and other cells to kill conventional microbes in vivo. Synthetic preparations containing HOCl can also be effective as microbial disinfectants. Here we have tested whether HOCl can also inactivate prions and other self-propagating protein amyloid seeds. Prions are deadly pathogens that are notoriously difficult to inactivate, and standard microbial disinfection protocols are often inadequate. Recommended treatments for prion decontamination include strongly basic (pH ≥~12) sodium hypochlorite bleach, ≥1 N sodium hydroxide, and/or prolonged autoclaving. These treatments are damaging and/or unsuitable for many clinical, agricultural and environmental applications. We have tested the anti-prion activity of a weakly acidic aqueous formulation of HOCl (BrioHOCl) that poses no apparent hazard to either users or many surfaces. For example, BrioHOCl can be applied directly to skin and mucous membranes and has been aerosolized to treat entire rooms without apparent deleterious effects. Here, we demonstrate that immersion in BrioHOCl can inactivate not only a range of target microbes, including spores of Bacillus subtilis, but also prions in tissue suspensions and on stainless steel. Real-time quaking-induced conversion (RT-QuIC) assays showed that BrioHOCl treatments eliminated all detectable prion seeding activity of human Creutzfeldt-Jakob disease, bovine spongiform encephalopathy, cervine chronic wasting disease, sheep scrapie and hamster scrapie; these findings indicated reductions of ≥103- to 106-fold. Transgenic mouse bioassays showed that all detectable hamster-adapted scrapie infectivity in brain homogenates or on steel wires was eliminated, representing reductions of ≥~105.75-fold and >104-fold, respectively. Inactivation of RT-QuIC seeding activity correlated with free chlorine concentration and higher order aggregation or destruction of proteins generally, including prion protein. BrioHOCl treatments had similar effects on amyloids composed of human α-synuclein and a fragment of human tau. These results indicate that HOCl can block the self-propagating activity of prions and other amyloids.
Studies have shown that the prevalence of RAS and BRAF mutations may differ by tumor sidedness among metastatic colorectal cancer (mCRC) patients. Both mutation status and tumor sidedness may impact survival and disease progression and RAS mutation status has been shown to predict response to anti-epidermal growth factor receptor (EGFR) therapy. A systematic literature review and meta-analysis were conducted to estimate the pooled prevalence of RAS and BRAF mutations by tumor sidedness in studies of mCRC patients. Forty-four studies comprising 15 981 mCRC patients tested for RAS and/or BRAF mutations were included in the meta-analyses. The prevalence of RAS mutations differed significantly by tumor side (32.4% among left-sided tumors, 41.3% among right-sided tumors; P = .017), as did the prevalence of KRAS mutations (35.8% among left-sided tumors, 46.3% among right-sided tumors; P < .0001) and BRAF mutations (4.3% among left-sided tumors, 16.3% among right-sided tumors; P < .0001). Among right-sided tumors, the prevalence of RAS and KRAS mutations varied significantly by study design, with higher prevalence among observational studies than clinical trials, and there was significant variation by study location for the prevalence of KRAS mutations in left-sided tumors and the prevalence of BRAF mutations in right-sided tumors. These results help to better characterize the mCRC population to better inform clinicians and researchers. Few of the included studies reported overall or progression-free survival (PFS) by both tumor sidedness and mutation status. As both of these factors may have prognostic impact, future studies should consider evaluating survival by these variables. K E Y W O R D S BRAF, KRAS, metastatic colorectal cancer, RAS, tumor sidedness | 1045 BYLSMA et AL. ORCID Lauren C. Bylsmahttps://orcid.
BackgroundOne established means of preventing the adverse consequences of malaria during pregnancy is sleeping under an insecticide treated net (ITN) throughout pregnancy. Despite increased access to this intervention over time, consistent ITN use during pregnancy remains relatively uncommon in sub-Saharan Africa.Methodology/Principal FindingsWe sought to identify determinants of ITN use during pregnancy. Utilizing a population-based random sample, we interviewed 500 women living in Jinja, Uganda, who had been pregnant in the past year. ITN ownership at the start of pregnancy was reported by 359 women (72%) and 28 women (20%) acquired an ITN after the first trimester of pregnancy. Among 387 ITN owners, 73% reported either always sleeping under the ITN during all trimesters of pregnancy, or after acquiring their net. Owning more than 1 net was slightly associated with always sleeping under an ITN during pregnancy (RR: 1.13; 95% CI: 1.00, 1.28). Women who always slept under an ITN during pregnancy were more likely to be influenced by an advertisement on the radio/poster than being given an ITN free of charge (RR: 1.48; 95% CI: 1.24, 1.76). No differences were found between other socio-demographic factors, pregnancy history, ANC use or socio-cultural factors.Conclusions/SignificanceWhile self-reported ITN ownership and use was common throughout pregnancy, we were unable to pinpoint why a sizable fraction of Ugandan women did not always adhere to recommendations for use of an ITN during pregnancy. More data are needed on the capacity of individual households to support the installation of ITNs which may provide insight into interventions targeted at improving the convenience and adherence of daily ITN use.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.