The structures of E. coli NfsA bound to the antibiotic nitrofurantoin; to 1,4-benzoquinone and to FMN

NfsA is a dimeric flavoprotein that catalyses the reduction in nitroaromatics and quinones by NADPH. This reduction is required for the activity of nitrofuran antibiotics. The crystal structure of free Escherichia coli NfsA and several homologues have been determined previously, but there is no structure of the enzyme with ligands. We present here crystal structures of oxidised E. coli NfsA in the presence of several ligands, including the antibiotic nitrofurantoin. Nitrofurantoin binds with the furan ring, rather than the nitro group that is reduced, near the N5 of the FMN. Molecular dynamics simulations show that this orientation is only favourable in the oxidised enzyme, while potentiometry suggests that little semiquinone is formed in the free protein. This suggests that the reduction occurs by direct hydride transfer from FMNH(−) to nitrofurantoin bound in the reverse orientation to that in the crystal structure. We present a model of nitrofurantoin bound to reduced NfsA in a viable hydride transfer orientation. The substrate 1,4-benzoquinone and the product hydroquinone are positioned close to the FMN N5 in the respective crystal structures with NfsA, suitable for reaction, but are mobile within the active site. The structure with a second FMN, bound as a ligand, shows that a mobile loop in the free protein forms a phosphate-binding pocket. NfsA is specific for NADPH and a similar conformational change, forming a phosphate-binding pocket, is likely to also occur with the natural cofactor

Methodological approaches to measuring mental health in a cost-of-living crisis: a rapid review

Background Cost-of-living crises are damaging to population mental health and require a public health response. It is important to assess whether public health interventions are effective. We aimed to identify population-level methods and measures and the appropriateness of the measures for vulnerable populations. Methods A rapid evidence review was undertaken. Nineteen databases, including grey literature, were searched for evidence published between 1970 and April 2023. Results Seven reviews, nine primary studies and two reports from grey literature were identified. Methods consisted of analyses of existing data from national or regional cohort studies, household panel surveys, repeated cross-sectional surveys, routine medical data, or data on suicide death rates. Twelve brief validated mental health measurement tools, embedded in population-level surveys, were identified. Two quasi-experimental studies used data from a UK household panel survey to examine the impact of the introduction of specific welfare policies on mental health. Studies identified socio-economic vulnerabilities, but it was not possible to determine whether data were effectively captured from people from minority ethnic groups. Conclusion Population-level surveys can be used in quasi-experimental studies to measure the effects of a public health initiative with specific roll out dates to tackle cost-of-living impacts. It is unclear as to whether the identified methods and tools are suitable for use with people from minority ethnic groups

Methodological approaches to measuring mental health in a cost-of-living crisis: A rapid review

BackgroundCost-of-living crises are damaging to population mental health and require a public health response. It is important to assess whether public health interventions are effective. We aimed to identify population-level methods and measures and the appropriateness of the measures for vulnerable populations.MethodsA rapid evidence review was undertaken. Nineteen databases, including grey literature, were searched for evidence published between 1970 and April 2023.ResultsSeven reviews, nine primary studies and two reports from grey literature were identified. Methods consisted of analyses of existing data from national or regional cohort studies, household panel surveys, repeated cross-sectional surveys, routine medical data, or data on suicide death rates. Twelve brief validated mental health measurement tools, embedded in population-level surveys, were identified. Two quasi-experimental studies used data from a UK household panel survey to examine the impact of the introduction of specific welfare policies on mental health. Studies identified socio-economic vulnerabilities, but it was not possible to determine whether data were effectively captured from people from minority ethnic groups.ConclusionPopulation-level surveys can be used in quasi-experimental studies to measure the effects of a public health initiative with specific roll out dates to tackle cost-of-living impacts. It is unclear as to whether the identified methods and tools are suitable for use with people from minority ethnic groups.<br/