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Gene therapy offers great promise in addressing neuropathologies associated with the central and peripheral nervous systems (CNS and PNS). However, genetic access remains difficult, reflecting the critical need for the development of effective and non-invasive gene delivery vectors across species. To that end, we evolved adeno-associated virus serotype 9 (AAV9) capsid in mice and validated two capsids, AAV-MaCPNS1 and AAV-MaCPNS2, across rodent species (mice and rats) and non-human primate (NHP) species (marmosets and rhesus macaques). Intravenous administration of either AAV efficiently transduced the PNS in rodents and both the PNS and CNS in NHPs. Furthermore, we used AAV-MaCPNS1 in mice to systemically deliver the following: (1) the neuronal sensor jGCaMP8s to record calcium signal dynamics in nodose ganglia and (2) the neuronal actuator DREADD to dorsal root ganglia to mediate pain. This conclusively demonstrates the translatability of these two systemic AAVs across four species and their functional utility through proof-of-concept studies in mice.

Integration of sensory and molecular inputs from the environment shapes animal behaviour. A major site of exposure to environmental molecules is the gastrointestinal tract, in which dietary components are chemically transformed by the microbiota1 and gut-derived metabolites are disseminated to all organs, including the brain2. In mice, the gut microbiota impacts behaviour3, modulates neurotransmitter production in the gut and brain4,5, and influences brain development and myelination patterns6,7. The mechanisms that mediate the gut-brain interactions remain poorly defined, although they broadly involve humoral or neuronal connections. We previously reported that the levels of the microbial metabolite 4-ethylphenyl sulfate (4EPS) were increased in a mouse model of atypical neurodevelopment8. Here we identified biosynthetic genes from the gut microbiome that mediate the conversion of dietary tyrosine to 4-ethylphenol (4EP), and bioengineered gut bacteria to selectively produce 4EPS in mice. 4EPS entered the brain and was associated with changes in region-specific activity and functional connectivity. Gene expression signatures revealed altered oligodendrocyte function in the brain, and 4EPS impaired oligodendrocyte maturation in mice and decreased oligodendrocyte-neuron interactions in ex vivo brain cultures. Mice colonized with 4EP-producing bacteria exhibited reduced myelination of neuronal axons. Altered myelination dynamics in the brain have been associated with behavioural outcomes7,9-14. Accordingly, we observed that mice exposed to 4EPS displayed anxiety-like behaviours, and pharmacological treatments that promote oligodendrocyte differentiation prevented the behavioural effects of 4EPS. These findings reveal that a gut-derived molecule influences complex behaviours in mice through effects on oligodendrocyte function and myelin patterning in the brain.

The infants of women with histories of problematic alcohol and other drug use are among the most vulnerable children known to statutory child protection services, which they enter at a younger age, and in which they remain longer. The net results include overwhelmed child protection systems and the birth of subsequent children conceived to ease women's grief at the loss their infants. Without adequate and appropriate support to the mother and her family, the pattern repeats. Obstetric services have an important role to play in the assessment of risk and protective factors in the perinatal period and in determining pathways to service provision. A comprehensive assessment considers the availability and quality of informal support prior to activation of formal systems of support, both statutory, where engagement is mandated, and non‐statutory, where support is offered on a voluntary basis. This paper uses quantitative methods to explore the social networks of women with problematic substance use in the transition to motherhood and the relationship between formal and informal support systems and infant outcomes. Surveys were held with two counsellors from the Women's Alcohol and Drug Service (WADS), a specialist obstetric clinic in Melbourne, Australia, and with 18 child protection workers. In addition, the Norbeck Social Support Questionnaire (Norbeck, 1984; Norbeck et al., 1983) was administered with 20 participating mothers to measure levels of formal and informal support, as well as the type and quality of support available to mothers over a 12‐month period, and to consider the provision of social support against known outcomes for infants. The findings demonstrate that WADS counsellors made several referrals for most women but that there was little in the way of long‐term follow‐up by non‐statutory service providers, with most women experiencing a dramatic drop in support over the 12‐month period. Women whose main informal support was from a domestically violent partner, and those who had been in out‐of‐home care in their own childhood, were particularly vulnerable to losing the care of their infant. The role of child protection varied markedly across the 12‐month period, particularly in relation to the extent that a relationship between formal and informal systems of support for mothers and their infants could be established. Overall, the study findings demonstrate that mothers experienced diminishing formal and informal support over time and that the quality of social support available to the mother was more important in terms of outcomes for women and their infants than the quantity. [ABSTRACT FROM AUTHOR]

Historically, information such as protocols and treatment pathways from specialist teams were shared with ward staff in paper format which proved cumbersome and difficult to update. Improvements were made with the addition of an intranet site, where protocols could be stored and accessed by clinical staff, however it was recognised that navigating the intranet site was not always straightforward and took up precious nursing time. The tissue viability team at the Royal United Hospitals NHS Foundation Trust (RUH) considered how such information might be made more readily available to clinicians. Inspired by widespread increased use of QR codes in public places during the COVID-19 pandemic, the team produced a poster containing multiple QR codes, enabling clinical staff to have instant access to wound care protocols as soon as the information was needed. [ABSTRACT FROM AUTHOR]

To examine the feasibility and acceptability of NIDUS-Family, a 6–8 session manualised, individually tailored, modular intervention supporting independence at home for people with dementia; and explore participants' and facilitators' experiences of the intervention. In this single group multi-site feasibility study, trained, supervised non-clinically qualified graduates (facilitators) delivered NIDUS-Family to family carer and people living with dementia dyads. We recruited participants from GP practices and memory services in London and Bradford. We completed quantitative outcomes pre- and post-intervention; and conducted qualitative interviews with participants and facilitators. Our pre-specified main outcomes were proportion of potential participants approached who agreed to participate, intervention adherence and acceptability to family carers, and facilitator fidelity to the manual. We recruited 16 dyads (57% of those approached); 12 (75%) completed the intervention. Of 12 participants rating intervention acceptability, 9 (75%) agreed or strongly agreed that it had helped; 2 (18%) neither agreed nor disagreed and 1 (8%) disagreed. Mean facilitator fidelity was high (81.5%). Dyads set on average 3.9 goals; these most commonly related to getting out and about and increasing activity/hobby participation (n = 10); carer wellbeing (n = 6), managing physical complaints (n = 6); meal preparation/cooking (n = 5); and reducing irritability, frustration or aggression (n = 5). Almost all secondary outcomes changed in a direction indicating improvement. In our qualitative analysis we identified three overarching themes; relationships facilitate change, goal-focused versus manualised approach and balancing the needs of carers and people with dementia. NIDUS-Family was feasible and acceptable to participants. Following refinements, testing in a pragmatic trial is underway. [ABSTRACT FROM AUTHOR]