Oncolytic viruses (OVs) promote the anti-tumor immune response as their replication, and the subsequent lysis of tumor cells, triggers the activation of immune-sensing pathways. Arming OVs by expressing transgenes with the potential to promote immune cell recruitment and activation is an attractive strategy to enhance OVs' therapeutic benefit. For picornaviruses, a family of OVs with clinical experience, the expression of a transgene is limited by multiple factors: genome physical packaging limits, high rates of recombination, and viral-mediated inhibition of transgene secretion.
View Article and Find Full Text PDFThe therapeutic effectiveness of oncolytic viruses (OVs) delivered intravenously is limited by the development of neutralizing antibody responses against the virus. To circumvent this limitation and to enable repeated systemic administration of OVs, here we develop Synthetic RNA viruses consisting of a viral RNA genome (vRNA) formulated within lipid nanoparticles. For two Synthetic RNA virus drug candidates, Seneca Valley virus (SVV) and Coxsackievirus A21, we demonstrate vRNA delivery and replication, virus assembly, spread and lysis of tumor cells leading to potent anti-tumor efficacy, even in the presence of OV neutralizing antibodies in the bloodstream.
View Article and Find Full Text PDFObjective: Assess the potential of hospital-wide routine screening by determining the prevalence and incidence of carbapenemase-producing organisms (CPOs) isolated from rectal screens at Barnet and Chase Farm Hospitals.
Methods: 3,553 samples were collected between 01/12/2018 and 31/08/2019: from adult critical care wards (universal screening - admission, discharge and weekly), from medical wards with risk-factor based screening according to the prevailing Public Health England (PHE) carbapenemase-producing Enterobacteriaceae (CPE) screening guidelines, or on an ad hoc basis. Prevalence was defined as previously documented positive CPO colonisation, or new positive status, as a proportion of all eligible samples.
Unlabelled: Carbapenemase-producing Enterobacteriaceae (CPE) are a significant challenge to healthcare and infection prevention and control teams. In the UK, OXA-48-like carbapenemases are frequently reported. We describe an outbreak of OXA-48-like producing Enterobacteriaceae and the control measures that proved effective in containing further spread.
View Article and Find Full Text PDFEclamptic seizures are a known complication of pregnancy; less well publicized is the patient with late postpartum eclampsia. Late postpartum eclamptic seizures are convulsions that occur more then 48 hours after delivery. Because 40% of patients who have late postpartum eclampsia do not experience preeclampsia, clinical awareness is essential for early treatment and care.
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