The World Health Organisation recently listed air pollution as the most significant threat to human health. Air pollution comprises particulate matter (PM), metals, black carbon and gases such as ozone (O 3 ), nitrogen dioxide (NO 2 ) and carbon monoxide (CO). In addition to respiratory and cardiovascular disease, PM exposure is linked with increased risk of neurodegeneration as well as neurodevelopmental impairments.Critically, studies suggest that PM crosses the placenta, making direct in utero exposure a reality. Rodent models reveal that neuroinflammation, neurotransmitter imbalance and oxidative stress are triggered following gestational/early life exposure to PM, and may be exacerbated by concomitant mitochondrial dysfunction. Gestational PM exposure (potentiated by mitochondrial impairment in the metabolically active neonatal brain) not only impacts neurodevelopment but may sensitise the brain to subsequent cognitive impairment. Having reviewed this field, we conclude that strategies are urgently required to reduce exposure to PM during this sensitive developmental period.

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ObjectivesThe potential for synergy between colistin and fusidic acid in the treatment of MDR Acinetobacter baumannii has recently been shown. The aim of this study was to perform an extensive in vitro characterization of this effect using pharmacokinetic-pharmacodynamic modelling (PKPD) of time–kill experiments in order to estimate clinical efficacy.MethodsFor six clinical strains, 312 individual time–kill experiments were performed including 113 unique pathogen–antimicrobial combinations. A wide range of concentrations (0.25–8192 mg/L for colistin and 1–8192 mg/L for fusidic acid) were explored, alone and in combination. PKPD modelling sought to quantify synergistic effects.ResultsA PKPD model confirmed synergy in that colistin EC50 was found to decrease by 83% in the presence of fusidic acid, and fusidic acid maximum increase in killing rate (Emax) also increased 58% in the presence of colistin. Simulations indicated, however, that at clinically achievable free concentrations, the combination may be bacteriostatic in colistin-susceptible strains, but growth inhibition probability was <20% in a colistin-resistant strain. ConclusionsFusidic acid may be a useful agent to add to colistin in a multidrug combination for MDR Acinetobacter baumannii.

Air pollution affects the majority of the world’s population and has been linked to over 7 million premature deaths per year. Exposure to particulate matter (PM) contained within air pollution is associated with cardiovascular, respiratory and neurological ill health. There is increasing evidence that exposure to air pollution in utero and in early childhood is associated with altered brain development. However, the underlying mechanisms for impaired brain development are not clear. While oxidative stress and neuroinflammation are documented consequences of PM exposure, cell-specific mechanisms that may be triggered in response to air pollution exposure are less well defined. Here we assess the effect of urban (U)PM exposure on two different cell types, microglial-like BV2 cells and neural stem / precursor-like C17.2 cells. We found that, contrary to expectations, immature C17.2 cells were more resistant to PM-mediated oxidative stress and cell death than BV2 cells. PM exposure resulted in decreased mitochondrial health and increased mitochondrial ROS in BV2 cells which could be prevented by mitoTEMPO antioxidant treatment. Our data suggest that not only is mitochondrial dysfunction a key trigger in PM-mediated cytotoxicity, but that such deleterious effects may also depend on cell type and maturity.