A multi-scale brain map derived from whole-brain volumetric reconstructions

Animal nervous system organization is crucial for all body functions and its disruption can lead to severe cognitive and behavioural impairment1. This organization relies on features across scales—from the localization of synapses at the nanoscale, through neurons, which possess intricate neuronal morphologies that underpin circuit organization, to stereotyped connections between different regions of the brain2. The sheer complexity of this organ means that the feat of reconstructing and modelling the structure of a complete nervous system that is integrated across all of these scales has yet to be achieved. Here we present a complete structure–function model of the main neuropil in the nematode Caenorhabditis elegans—the nerve ring—which we derive by integrating the volumetric reconstructions from two animals with corresponding3 synaptic and gap-junctional connectomes. Whereas previously the nerve ring was considered to be a densely packed tract of neural processes, we uncover internal organization and show how local neighbourhoods spatially constrain and support the synaptic connectome. We find that the C. elegans connectome is not invariant, but that a precisely wired core circuit is embedded in a background of variable connectivity, and identify a candidate reference connectome for the core circuit. Using this reference, we propose a modular network architecture of the C. elegans brain that supports sensory computation and integration, sensorimotor convergence and brain-wide coordination. These findings reveal scalable and robust features of brain organization that may be universal across phyla

Therapeutic DNA vaccine induces broad T cell responses in the gut and sustained protection from viral rebound and AIDS in SIV-infected rhesus macaques.

Immunotherapies that induce durable immune control of chronic HIV infection may eliminate the need for life-long dependence on drugs. We investigated a DNA vaccine formulated with a novel genetic adjuvant that stimulates immune responses in the blood and gut for the ability to improve therapy in rhesus macaques chronically infected with SIV. Using the SIV-macaque model for AIDS, we show that epidermal co-delivery of plasmids expressing SIV Gag, RT, Nef and Env, and the mucosal adjuvant, heat-labile E. coli enterotoxin (LT), during antiretroviral therapy (ART) induced a substantial 2-4-log fold reduction in mean virus burden in both the gut and blood when compared to unvaccinated controls and provided durable protection from viral rebound and disease progression after the drug was discontinued. This effect was associated with significant increases in IFN-γ T cell responses in both the blood and gut and SIV-specific CD8+ T cells with dual TNF-α and cytolytic effector functions in the blood. Importantly, a broader specificity in the T cell response seen in the gut, but not the blood, significantly correlated with a reduction in virus production in mucosal tissues and a lower virus burden in plasma. We conclude that immunizing with vaccines that induce immune responses in mucosal gut tissue could reduce residual viral reservoirs during drug therapy and improve long-term treatment of HIV infection in humans

Direct glia-to-neuron transdifferentiation gives rise to a pair of male-specific neurons that ensure nimble male mating

Sexually dimorphic behaviours require underlying differences in the nervous system between males and females. The extent to which nervous systems are sexually dimorphic and the cellular and molecular mechanisms that regulate these differences are only beginning to be understood. We reveal here a novel mechanism by which male-specific neurons are generated in Caenorhabditis elegans through the direct transdifferentiation of sex-shared glial cells. This glia-to-neuron cell fate switch occurs during male sexual maturation under the cell-autonomous control of the sex-determination pathway. We show that the neurons generated are cholinergic, peptidergic, and ciliated putative proprioceptors which integrate into male-specific circuits for copulation. These neurons ensure coordinated backward movement along the mate’s body during mating. One step of the mating sequence regulated by these neurons is an alternative readjustment movement performed when intromission becomes difficult to achieve. Our findings reveal programmed transdifferentiation as a developmental mechanism underlying flexibility in innate behaviour

Pressure Ulcer and Wounds Reporting in NHS Hospitals in England Part 1: Audit of Monitoring Systems

Internationally, health-care systems have attempted to assess the scale of and demonstrate improvement in patient harms. Pressure ulcer (PU) monitoring systems have been introduced across NHS in-patient facilities in England, including the Safety Thermometer (STh) (prevalence), Incident Reporting Systems (IRS) and the Strategic Executive Information System (STEIS) for serious incidents. This is the first of two related papers considering PU monitoring systems across NHS in-patient facilities in England and focusses on a Wound Audit (PUWA) to assess the accuracy of these systems. Part 2 of this work and recommendations are reported pp *-*. The PUWA was undertaken in line with ‘gold-standard’ PU prevalence methods in a stratified random sample of NHS Trusts; 24/34(72.7%) invited NHS Trusts participated, from which 121 randomly selected wards and 2239 patients agreed to participate. Prevalence of existing PUs: The PUWA identified 160(7.1%) patients with an existing PU, compared to 105(4.7%) on STh. STh had a weighted sensitivity of 48.2%(95%CI 35.4%-56.7%) and weighted specificity of 99.0%(95%CI 98.99%-99.01%). Existing/healed PUs: The PUWA identified 189(8.4%) patients with an existing/healed PU compared to 135(6.0%) on IRS. IRS had an unweighted sensitivity of 53.4%(95%CI 46.3% to 60.4%) and unweighted specificity of 98.3% (95%CI 97.7% to 98.8%). 83 patients had one or more potentially serious PU on PUWA and 8(9.6%) of these patients were reported on STEIS. The results identified high levels of under-reporting for all systems and highlighted data capture challenges, including the use of clinical staff to inform national monitoring systems and the completeness of clinical records for PUs

Workplace wellness using online learning tools in a healthcare setting

The aim was to develop and evaluate an online learning tool for use with UK healthcare employees, healthcare educators and healthcare students, to increase knowledge of workplace wellness as an important public health issue. A ‘Workplace Wellness’ e-learning tool was developed and peer-reviewed by 14 topic experts. This focused on six key areas relating to workplace wellness: work-related stress, musculoskeletal disorders, diet and nutrition, physical activity, smoking and alcohol consumption. Each key area provided current evidence-based information on causes and consequences, access to UK government reports and national statistics, and guidance on actions that could be taken to improve health within a workplace setting. 188 users (93.1% female, age 18–60) completed online knowledge questionnaires before (n = 188) and after (n = 88) exposure to the online learning tool. Baseline knowledge of workplace wellness was poor (n = 188; mean accuracy 47.6%, s.d. 11.94). Knowledge significantly improved from baseline to post-intervention (mean accuracy = 77.5%, s.d. 13.71) (t(75) = −14.801, p < 0.0005) with knowledge increases evident for all included topics areas. Usability evaluation showed that participants perceived the tool to be useful (96.4%), engaging (73.8%) and would recommend it to others (86.9%). Healthcare professionals, healthcare educators and pre-registered healthcare students held positive attitudes towards online learning, indicating scope for development of further online packages relating to other important health parameters