Re-valuation of annual cytology using HPV self-sampling to upgrade prevention (REACH UP): A feasibility study in women living with HIV in the UK

Introduction: Current UK guidelines for cervical cancer screening are based on the assumption that most women living with HIV (WLWH) are also high-risk (HR) human papillomavirus (HPV)-positive. We aimed to provide data on prevalence of HR-HPV in WLWH in the UK and to assess feasibility and acceptability of HR-HPV self-sampling in this group. // Methods: Women living with HIV attending six HIV services in London/south of England, with no history of cervical cancer, were enrolled. Participants self-collected a vaginal swab for the detection of HR-HPV, completed a survey about sexual/gynaecological history, attitudes towards annual screening and perception of HR-HPV self-sampling, and were asked to have their annual cervical smear. // Results: In all, 67 women were included: 86.5% were of black ethnicity, the median (range) age was 47 (24–60) years, median CD4 T-cell count was 683 cells/µL [interquartile range (IQR): 527–910], and 95.4% had viral load ≤ 50 copies/mL. All performed the vaginal swab. Eighteen (27%) had no cervical smear results; none of these women attended HIV services where this was routinely offered. No cervical samples were positive for HR-HPV. Three-quarters (75.8%) of participants reported adherence to annual screening, with only one woman (1.5%) attending irregularly. On visual analogue scales (from 0 to 100), median (IQR) acceptability and necessity of smear tests were 100 (75–100) and 100 (85–100), respectively. // Conclusions: Our results suggest that the prevalence of HR-HPV in WLWH in the UK may be low. Self-sampling seems to be acceptable, suggesting, if validated, its potential role in supporting less frequent smear testing and improving screening uptake in WLW

Assessment of Coagulation–Flocculation Process Efficiency for the Natural Organic Matter Removal in Drinking Water Treatment

Natural organic matter (NOM) represents a range of heterogeneous hydrophobic and hydrophilic components naturally occurring in the water source and, due to the fact that they can act as precursors for the disinfection, by-products may have a considerable impact on drinking water quality. Coagulation–flocculation (C/F) is among the most applied processes for NOM removal from water sources (especially rivers). In this study, C/F efficiency for a river water supply was investigated in cold and warm conditions, by varying the coagulant dose and mixing conditions. In this study, polyhydroxy aluminum chloride PAX XL 60, and polyacrylamide FloPam AN 910 SEP were used as coagulant and flocculant, respectively. Multiple water quality indicators were determined, such as turbidity, chemical oxygen demand (COD), dissolved organic carbon (DOC), and residual aluminum concentration. Some unconventional parameters relevant for NOM removal were also considered, like absorbance at 254 nm (A254), at 280 nm (A280), and at 365 nm (A365), as well as the ratios A254/DOC, A254/280, and A254/A365. After coagulation–flocculation, turbidity was completely removed in all the studied conditions. The DOC content was reduced by up to 22.65% at a low temperature and by up to 31.81% at a high temperature. After the addition of polyelectrolyte in cold conditions, the efficiency in terms of A254 increased by up to 37.4%, while the specific absorbance decreased. The high molecular weight NOM increased after C/F, based on the A254/A365 ratio. Chemometric analysis was employed in order to determine the effect of the coagulant dose on the process efficiency. The optimum coagulation–flocculation conditions were corroborated by means of the principal component analysis

In vivo RNAi screening identifies a mechanism of sorafenib resistance in liver cancer

In solid tumors, resistance to therapy inevitably develops upon treatment with cytotoxic drugs or molecularly targeted therapies. Here, we describe a system that enables pooled shRNA screening directly in mouse hepatocellular carcinomas (HCC) in vivo to identify genes likely to be involved in therapy resistance. Using a focused shRNA library targeting genes located within focal genomic amplifications of human HCC, we screened for genes whose inhibition increased the therapeutic efficacy of the multikinase inhibitor sorafenib. Both shRNA-mediated and pharmacological silencing of Mapk14 (p38alpha) were found to sensitize mouse HCC to sorafenib therapy and prolong survival by abrogating Mapk14-dependent activation of Mek-Erk and Atf2 signaling. Elevated Mapk14-Atf2 signaling predicted poor response to sorafenib therapy in human HCC, and sorafenib resistance of p-Mapk14-expressing HCC cells could be reverted by silencing Mapk14. Our results suggest that a combination of sorafenib and Mapk14 blockade is a promising approach to overcoming therapy resistance of human HCC