RESUMEN
Extrachromosomal (ec) DNAs are genetic elements that exist separately from the genome. Since ecDNA can carry beneficial genes, they are a powerful adaptive mechanism in cancers and many pathogens. For the first time, we report ecDNA contributing to antimalarial resistance in Plasmodium falciparum, the most virulent human malaria parasite. Using pulse field gel electrophoresis combined with PCR-based copy number analysis, we detected two ecDNA elements that differ in migration and structure. Entrapment in the electrophoresis well and low susceptibility to exonucleases revealed that the biologically relevant ecDNA element is large and complex in structure. Using deep sequencing, we show that ecDNA originates from the chromosome and expansion of an ecDNA-specific sequence may improve its segregation or expression. We speculate that ecDNA is maintained using established mechanisms due to shared characteristics with the mitochondrial genome. Implications of ecDNA discovery in this organism are wide-reaching due to the potential for new strategies to target resistance development.
Asunto(s)
Resistencia a Medicamentos/genética , Genoma de Protozoos , Malaria Falciparum/prevención & control , Malaria Falciparum/parasitología , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/genética , Adaptación Fisiológica , Antimaláricos/farmacología , ADN Protozoario , Amplificación de Genes , Humanos , Pirimidinas/farmacologíaRESUMEN
PURPOSE: Recommendations for exclusive breastfeeding are not often adhered to despite the robust evidence of its benefits. This systematic review aims to collate evidence on the attitudes mothers and health care providers have towards breastfeeding interventions to understand what aspects best contribute to acceptability and feasibility. METHODS: This review further investigates the value of identifiable behaviour change techniques (BCTs) to uncover which components of an intervention are perceived to be most useful and acceptable. The main biomedical databases were searched, and 17 (n = 17) studies met the inclusion criteria. RESULTS: A total of nine BCTs were identified within the interventions. The thematic analysis produced four main domains: usefulness, accessibility, value and sustainability. Women discussed the importance of the support they received in these interventions and demonstrated a positive view towards three BCTs: 'social support (unspecified)', 'instruction on how to perform behaviour' and 'demonstration of behaviour'. Additionally, women highlighted the benefit of personal, non-clinical and flexible emotional and practical support from peers, lactation consultants and support groups. Health care providers echoed these opinions and specifically highlighted the usefulness of interventions that allowed for continuity of care and more personal breastfeeding support. CONCLUSIONS: These findings suggest that ongoing practical as well as emotional support is crucial for standard in-hospital support to succeed at increasing breastfeeding rates. Future research would need to better understand the nuances of the interventions among women and providers to enhance their implementation.