Adverse exposures that influence growth in prenatal and early postnatal periods are considered to influence vulnerability to chronic diseases via their effects on the neuroendocrine system. In humans, the assessment of the underlying mechanisms has been restricted. The present study aimed to investigate the effects of adverse early-life exposures, specifically maternal mood, on hypothlamic-pituitary-adrenal (HPA) axis, sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) responses to an acute physiological stressor. In addition, we conducted a preliminary examination into whether these effects varied by time of exposure and sex. One hundred and thity-nine individuals (mean age 15.12 years) were recruited from the ALSPAC (Avon Longitudinal Study of Parents and Children) birth cohort. Participants underwent the CO(2) stress test and indices of the PNS, SNS and HPA axis were measured. Pre-existing data on demographic and psychosocial factors of the mothers during pregnancy (18 and 32 weeks) and postnatally (8 weeks and 8 months) were extracted, as were participants' clinical and demographic data at birth. Increases in both pre- and postnatal anxiety and depression were associated with greater SNS reactivity to the stressor and slower recovery, as well as blunted HPA axis responses. Programming effects on the SNS appeared to be restricted to male offspring only. No consistent relationships were evident for any of the measures of pre-stress function. We have found preliminary evidence that both pre- and postnatal maternal anxiety and depression have sustained programming effects on the SNS and HPA axis. Effects on the SNS were restricted to male offspring.

Background: Patient registries represent an important method of organizing "real world" patient information for clinical and research purposes. Registries can facilitate clinical trial planning and recruitment and are particularly useful in this regard for uncommon and rare diseases. Neuromuscular diseases (NMDs) are individually rare but in aggregate have a significant prevalence. In Canada, information on NMDs is lacking. Barriers to performing Canadian multicentre NMD research exist which can be overcome by a comprehensive and collaborative NMD registry. Methods: We describe the objectives, design, feasibility and initial recruitment results for the Canadian Neuromuscular Disease Registry (CNDR). Results: The CNDR is a clinic-based registry which launched nationally in June 2011, incorporates paediatric and adult neuromuscular clinics in British Columbia, Alberta, Ontario, Quebec, New Brunswick and Nova Scotia and, as of December 2012, has recruited 1161 patients from 12 provinces and territories. Complete medical datasets have been captured on 460 "index disease" patients. Another 618 "non-index" patients have been recruited with capture of physicianconfirmed diagnosis and contact information. We have demonstrated the feasibility of blended clinic and central office-based recruitment. "Index disease" patients recruited at the time of writing include 253 with Duchenne and Becker muscular dystrophy, 161 with myotonic dystrophy, and 71 with ALS. Conclusions: The CNDR is a new nationwide registry of patients with NMDs that represents an important advance in Canadian neuromuscular disease research capacity. It provides an innovative platform for organizing patient information to facilitate clinical research and to expedite translation of recent laboratory findings into human studies.RÉSUMÉ: Le RCMN : collaborer pour procurer de nouveaux traitements aux Canadiens. Contexte : Un registre de patients est une façon très avantageuse d'organiser l'information concrète au sujet de patients à des fins cliniques ou de recherche. Les registres peuvent faciliter la planification d'essais cliniques et le recrutement et sont particulièrement utiles à cet égard quand il s'agit de maladies rares. Les maladies neuromusculaires (MNM) considérées individuellement sont des maladies rares mais elles ont une prévalence non négligeable si elles sont regroupées. Au Canada, on manque d'informations sur les MNM. Il existe des obstacles à la réalisation de recherches multicentriques sur les MNM au Canada. Ces obstacles peuvent être surmontés par l'établissement d'un registre détaillé à des fins de collaboration sur les MNM. Méthode : Nous décrivons les objectifs, le plan, la faisabilité et les résultats du recrutement initial du Registre canadien des maladies neuromusculaires. Résultats : Le RCMN est un registre basé sur la clinique qui a été inauguré à travers le Canada en juin 2011. Il inclut des cliniques neuromusculaires pédiatriques et adultes et inclut des patients de Colombie-Britannique, d'Alberta, de l'Ontario, du Québe...

The low activity allele of the maternal polymorphism, 5HTTLPR, in the serotonin transporter, SLC6A4, coupled with prenatal stress is reported to increase the risk for children to develop autism spectrum disorder (ASD). Similarly, maternal Slc6a4 knock-out and prenatal stress in rodents results in offspring demonstrating ASD-like characteristics. The present study uses an integrative genomics approach to explore mechanistic changes in early brain development in mouse embryos exposed to this maternal gene-environment phenomenon. Restraint stress was applied to pregnant Slc6a4 +/+ and Slc6a4 +/− mice and post-stress embryonic brains were assessed for whole genome level profiling of methylome, transcriptome and miRNA using Next Generation Sequencing. Embryos of stressed Slc6a4 +/+ dams exhibited significantly altered methylation profiles and differential expression of 157 miRNAs and 1009 genes affecting neuron development and cellular adhesion pathways, which may function as a coping mechanism to prenatal stress. In striking contrast, the response of embryos of stressed Slc6a4 +/− dams was found to be attenuated, shown by significantly reduced numbers of differentially expressed genes (458) and miRNA (0) and genome hypermethylation. This attenuated response may pose increased risks on typical brain development resulting in development of ASD-like characteristics in offspring of mothers with deficits in serotonin related pathways during stressful pregnancies.

Despite the significant differences between medical and dental practitioners in undergraduate and postgraduate training in orofacial disease, most patients would choose to visit a medical rather than dental practitioner. While these results suggest the need for postgraduate educational support for medical practitioners in treating orofacial pain and oral mucosal disease, they also imply a need for change in the concept of provision of oral healthcare by general dental practitioners.