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Changing epidemiology of Plasmodium vivax malaria in Nouakchott, Mauritania: a six-year (2015–2020) prospective study | Malaria Journal

Plasmodium vivax malaria is one of the major infectious diseases of public health concern in Nouakchott, the capital city of Mauritania and the biggest urban setting in the Sahara. The assessment of the current trends in malaria epidemiology is primordial in understanding the dynamics of its transmission and developing an effective control strategy. A 6 year (2015–2020) prospective study was carried out in Nouakchott. Febrile outpatients with a clinical suspicion of malaria presenting spontaneously at Teyarett Health Centre or the paediatric department of Mother and Children Hospital Centre were screened for malaria using a rapid diagnostic test, microscopic examination of Giemsa-stained blood films, and nested polymerase chain reaction. Data were analysed using Microsoft Excel and GraphPad Prism and InStat software. Of 1760 febrile patients included in this study, 274 (15.5%) were malaria-positive by rapid diagnostic test, 256 (14.5%) were malaria-positive by microscopy

CYP2B6 Phenotypic correlation of Efavirenz therapy

The stability of R-spine defines RAF inhibitor resistance: A comprehensive analysis of oncogenic BRAF mutants with in-frame insertion of αC-β4 loop

Although targeting BRAF mutants with RAF inhibitors has achieved promising outcomes in cancer therapy, drug resistance remains a remarkable challenge, and underlying molecular mechanisms are not fully understood. Here, we characterized a previously unknown group of oncogenic BRAF mutants with in-frame insertions (LLRins506 or VLRins506) of αC-β4 loop. Using structure modeling and molecular dynamics simulation, we found that these insertions formed a large hydrophobic network that stabilizes R-spine and thus triggers the catalytic activity of BRAF. Furthermore, these insertions disrupted BRAF dimer interface and impaired dimerization. Unlike BRAF(V600E), these BRAF mutants with low dimer affinity were strongly resistant to all RAF inhibitors in clinic or clinical trials, which arises from their stabilized R-spines. As predicted by molecular docking, the stabilized R-spines in other BRAF mutants also conferred drug resistance. Together, our data indicated that the stability of R-spine

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