The cellular composition of the human immune system is shaped by age and cohabitation.

Detailed population-level description of the human immune system has recently become achievable. We used a 'systems-level' approach to establish a resource of cellular immune profiles of 670 healthy individuals. We report a high level of interindividual variation, with low longitudinal variation, at the level of cellular subset composition of the immune system. Despite the profound effects of antigen exposure on individual antigen-specific clones, the cellular subset structure proved highly elastic, with transient vaccination-induced changes followed by a return to the individual's unique baseline. Notably, the largest influence on immunological variation identified was cohabitation, with 50% less immunological variation between individuals who share an environment (as parents) than between people in the wider population. These results identify local environmental conditions as a key factor in shaping the human immune system

Innovation and Design of a Web-Based Pain Education Interprofessional Resource

INTRODUCTION: The present article describes educational innovation processes and design of a web-based pain interprofessional resource for prelicensure health science students in universities across Canada. Operationalization of educational theory in design coupled with formative evaluation of design are discussed, along with strategies that support collaborative innovation.METHODS: Educational design was driven by content, theory and evaluation. Pain misbeliefs and teaching points along the continuum from acute to persistent pain were identified. Knowledge-building theory, situated learning, reflection and novel designs for cognitive scaffolding were then employed. Design research principles were incorporated to inform iterative and ongoing design.RESULTS: An authentic patient case was constructed, situated in inter-professional complex care to highlight learning objectives related to pre-operative, postoperative and treatment up to one year, for a surgical cancer patient. Pain mechanisms, assessment and management framed content creation. Knowledge building scaffolds were used, which included video simulations, embedded resources, concurrent feedback, practice-based reflective exercises and commentaries. Scaffolds were refined to specifically support knowledge translation. Illustrative commentaries were designed to explicate pain misbeliefs and best practices. Architecture of the resource was mapped; a multimedia, interactive prototype was created. This pain education resource was developed primarily for individual use, with extensions for interprofessional collective discourse.DISCUSSION: Translation of curricular content scripts into representation maps supported the collaborative design process by establishing a common visual language. The web-based prototype will be formatively and summatively evaluated to assess pedagogic design, knowledge-translation scaffolds, pain knowledge gains, relevance, feasibility and fidelity of this educational innovation.Peer Reviewe

Subdiaphragmatic Vagotomy Prevents Drinking-Induced Reduction in Plasma Corticosterone in Water-Restricted Rats

Dehydrated rats exhibit a rapid inhibition of the hypothalamic-pituitary-adrenal axis after rehydration. Drinking activates vagal afferents that project to neurons in the nucleus tractus solitarius (NTS). We hypothesized that when dehydrated rats drink, vagal afferents stimulate NTS neurons initiating inhibition of hypothalamic-pituitary-adrenal activity. Experiments assessed NTS activity by measuring Fos expression. Rats were water restricted for 1 or 6 d, limiting access to water to 30 min/d in the morning. Drinking after single or repeated restriction increased Fos, demonstrating increased NTS activity. We next examined the contribution of the vagus by comparing hormonal responses after total subdiaphragmatic vagotomy or sham surgery. Water restriction for 6 d increased plasma arginine vasopressin (AVP), ACTH, and adrenal and plasma corticosterone in both groups. In sham rats, drinking reduced plasma AVP, ACTH, adrenal and plasma corticosterone by 7.5 min. In total subdiaphragmatic vagotomy rats, whereas drinking reduced plasma AVP, ACTH, and adrenal corticosterone, drinking did not reduce plasma corticosterone. To identify the source of vagal activity, hormonal responses to restriction-induced drinking were measured after common hepatic branch vagotomy (HBV). Although pituitary hormonal responses were not affected by HBV, the adrenal and plasma corticosterone responses to water restriction were reduced; in addition, drinking in HBV rats decreased adrenal corticosterone without changing plasma corticosterone. These data indicate that an intact vagus is necessary to reduce plasma corticosterone when water-restricted rats drink and that the common hepatic vagal branch contributes to the response. These findings implicate the vagus in augmenting rapid removal of circulating corticosterone during relief from stress

Summary of recruitment statistics across seven international study sites for the TRACK-FA study.

The target recruitment and the cumulative total of FRDA and control participants currently recruited into the study (categorised into the age groups) have been indicated.</p

TRACK-FA protocol used to obtain cervical spinal cord and brain MRI data.

TRACK-FA protocol used to obtain cervical spinal cord and brain MRI data.</p

Neurologic and functional measures completed by TRACK-FA participants.

Neurologic and functional measures completed by TRACK-FA participants.</p

The FARS Functional Staging for Ataxia scale describing the clinical presentation at each stage.

The FARS Functional Staging for Ataxia scale describing the clinical presentation at each stage.</p