31 research outputs found

    A whole cell pathway screen reveals seven novel chemosensitizers to combat chloroquine resistant malaria

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    Due to the widespread prevalence of resistant parasites, chloroquine (CQ) was removed from front-line antimalarial chemotherapy in the 1990s despite its initial promise of disease eradication. Since then, resistance-conferring mutations have been identified in transporters such as the PfCRT, that allow for the efflux of CQ from its primary site of action, the parasite digestive vacuole. Chemosensitizing/ chemoreversing compounds interfere with the function of these transporters thereby sensitizing parasites to CQ once again. However, compounds identified thus far have disappointing in vivo efficacy and screening for alternative candidates is required to revive this strategy. In this study, we propose a simple and direct means to rapidly screen for such compounds using a fluorescent-tagged CQ molecule. When this screen was applied to a small library, seven novel chemosensitizers (octoclothepin, methiothepin, metergoline, loperamide, chlorprothixene, L-703,606 and mibefradil) were quickly elucidated, including two which showed greater potency than the classical chemosensitizers verapamil and desipramine

    CAR-T cell. the long and winding road to solid tumors

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    Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles

    A comparison of the job-satisfied and job-dissatisfied environmental health officer in South Africa.

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    AlgemeenSentrum vir Studentevoorligting en ïżœontwikkeling (SSVO)Please help us populate SUNScholar with the post print version of this article. It can be e-mailed to: [email protected]

    Technical and economic evaluation of the separation of alkanes and alcohols with supercritical fluids.

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    Please help us populate SUNScholar with the post print version of this article. It can be e-mailed to: [email protected]

    Lynch syndrome screening in gynaecological cancers: results of an international survey with recommendations for uniform reporting terminology for mismatch repair immunohistochemistry results

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    Aim Lynch Syndrome (LS) is associated with an increased risk of developing endometrial carcinoma (EC) and ovarian carcinoma (OC). There is considerable variability in current practices and opinions related to screening newly diagnosed patients with EC/OC for LS. An online survey was undertaken to explore the extent of these differences. Methods An online questionnaire was developed by a panel of experts and sent to all members of the British Association of Gynaecological Pathologists (BAGP) and the International Society of Gynecological Pathologists (ISGyP). Anonymised results were received and analyzed. Results Thirty‐six BAGP and 44 ISGyP members completed the survey. More than 90% of respondents were aware of the association of LS with both EC and OC, but 34% were not aware of specific guidelines for LS screening. Seventy‐one percent of respondents agreed that universal screening for LS should be carried out in all newly diagnosed EC cases, with immunohistochemistry (IHC) alone as the preferred approach. Only 36% of respondents currently performed IHC or microsatellite instability testing on all newly diagnosed EC, with most of the remaining respondents practicing selective screening, based on clinical or pathological features or both. A significant minority of respondents (35%) believed that patient consent was required before performing MMR IHC. Almost all respondents favored use of standardized terminology for reporting MMR staining results and this is proposed herein. Conclusion There is wide support for universal LS screening in patients with EC, but this survey highlights areas of considerable variation in practice

    Bond strength of resin-resin interfaces contaminated with saliva and submitted to different surface treatments

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    The purpose of this study was to investigate the effect of different surface treatments on shear bond strength of saliva-contaminated resin-resin interfaces. Flat resin surfaces were fabricated. In the control group, no contamination or surface treatment was performed. The resin surfaces of the experimental groups were contaminated with saliva and air-dried, and then submitted to: (G1) rinsing with water and drying; (G2) application of an adhesive system; (G3) rinsing and drying, abrasion with finishing disks, etching and application of adhesive system; (G4) rinsing and drying, etching, application of silane and adhesive system. Resin cylinders were placed over the treated surfaces. The specimens were stored in water or ethanol. Shear bond strength tests were performed and the mode of failure was evaluated. Data were submitted to two-way ANOVA and Dunnett T3 test. Contamination of resin-resin interfaces with saliva significantly reduced shear strength, especially after prolonged storage (p<0.05). Similar values to the original bond strength were obtained after abrasion and application of adhesive (G3) or etching and application of silane and adhesive (G4). If contamination occurs, a surface treatment is required to guarantee an adequate interaction between the resin increments
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