Background: Surgical resection of vestibular schwannoma (VS) is often curative if gross total resection is achieved, however, it is a delicate procedure with high risk to the facial nerve. With retrosigmoid approach for resection, the head is positioned to maximize lateral head rotation and neck flexion in order to optimize the surgical field. However, this may inadvertently occlude cerebral venous drainage, elevating intracranial pressure (ICP) and increasing intraoperative bleeding. Methods: Here, we review relevant literature regarding the effects of head rotation and neck flexion on internal jugular vein (IJV) occlusion and ICP, and highlight the notion that head rotation and flexion may occlude the ipsilateral IJV, increasing ICP. Subsequently, we propose a novel technique using continuous, real-time monitoring of jugular bulb pressure (JBP) to detect obstructions in jugular venous flow and guide optimal head positioning prior to VS resection. Results: As proof of concept, we present a case in which JBP monitoring was employed to optimize head positioning prior to a VS resection, which shows a significant reduction in JBP compared to traditional positioning. Conclusions: This innovative approach offers promise in enhancing the safety and efficacy of intracranial surgery for VS and potentially other neurosurgical procedures.

Maternal antenatal depression strongly influences child mental health but with considerable inter-individual variation that is, in part, linked to genotype. The challenge is to effectively capture the genotypic influence. We outline a novel approach to describe genomic susceptibility to maternal antenatal depression focusing on child emotional/behavioral difficulties. Two cohorts provided measures of maternal depression, child genetic variation, and child mental health symptoms. We constructed a conventional polygenic risk score (PRS) for attention-deficit/hyperactivity disorder (ADHD) (PRSADHD) that significantly moderated the association between maternal antenatal depression and internalizing problems at 60 months (p = 2.94 × 10−4, R2 = .18). We then constructed an interaction PRS (xPRS) based on a subset of those single nucleotide polymorphisms from the PRSADHD that most accounted for the moderation of the association between maternal antenatal depression and child outcome. The interaction between maternal antenatal depression and this xPRS accounted for a larger proportion of the variance in child emotional/behavioral problems than models based on any PRSADHD (p = 5.50 × 10−9, R2 = .27), with similar findings in the replication cohort. The xPRS was significantly enriched for genes involved in neuronal development and synaptic function. Our study illustrates a novel approach to the study of genotypic moderation on the impact of maternal antenatal depression on child mental health and highlights the utility of the xPRS approach. These findings advance our understanding of individual differences in the developmental origins of mental health.

Stress elicits adaptive responses from the brain, but it can also lead to maladaptive consequences. For example, stress can precipitate mental illness, including depression. Prolonged stress also causes damage to neurons in the hippocampus. Antidepressant drugs must be evaluated, not only for their ability to potentiate adaptive responses, but also to inhibit maladaptive consequences of stress. Ongoing research in our laboratory has compared the atypical tricyclic antidepressant, tianeptine, with the typical tricyclics, desipramine and imipramine, with respect to the effects of isolation and repeated restraint stress. Tianeptine and desipramine similarly attenuated isolation stress-induced increases in locus coeruleus and midbrain tyrosine hydroxylase mRNA levels and isolation-stress induced decreases in preproenkephalin mRNA levels in striatum and nucleus accumbens. However, tianeptine and imipramine differed in their effects in the cerebral cortex and hippocampus on 5HT2, and 5HT1A receptor levels but, surprisingly, produced similar effects on levels of the serotonin transporter labelled with [3H] paroxetine. Tianeptine also prevented stress-induced reductions in the length and number of branchpoints of dendrites of CA3 pyramidal neurons in hippocampus; comparison with effects of typical tricyclics are ongoing. Tianeptine also blocked effects of corticosterone treatment to reduce branching and length of CA3 dendrites. These actions of tianeptine may be due to interactions between 5HT and excitatory amino acids in the mossy fiber terminals on CA3 pyramidal neurons. Taken together, these results indicate that tianeptine has unique properties compared to some other antidepressant drugs, but shares in common with those drugs the ability to attenuate stress effects on tyrosine hydroxylase gene expression and on the serotonin transporter. It remains to be seen whether these actions are the basis of a common antidepressant action.

Norovirus is a predominant cause of infectious gastroenteritis in countries worldwide [1–5]. It accounts for approximately 50% of acute gastroenteritis (AGE) and >90% of viral gastroenteritis outbreaks [6, 7]. The incubation period ranges between 10 and 48 h and illness duration is generally 1–3 days with self-limiting symptoms; however, this duration is often longer (e.g. 4–6 days) in vulnerable populations such as hospital patients or young children [2, 8]. Symptomatic infection of norovirus presents as acute vomiting, diarrhoea, abdominal cramps and nausea, with severe vomiting and diarrhoea (non-bloody) being most common [2, 5, 9].

Prenatal adversity shapes child neurodevelopment and risk for later mental health problems. The quality of the early care environment can buffer some of the negative effects of prenatal adversity on child development. Retrospective studies, in adult samples, highlight epigenetic modifications as sentinel markers of the quality of the early care environment; however, comparable data from pediatric cohorts are lacking. Participants were drawn from the Maternal Adversity Vulnerability and Neurodevelopment (MAVAN) study, a longitudinal cohort with measures of infant attachment, infant development, and child mental health. Children provided buccal epithelial samples (mean age = 6.99, SD = 1.33 years, n = 226), which were used for analyses of genome-wide DNA methylation and genetic variation. We used a series of linear models to describe the association between infant attachment and (a) measures of child outcome and (b) DNA methylation across the genome. Paired genetic data was used to determine the genetic contribution to DNA methylation at attachment-associated sites. Infant attachment style was associated with infant cognitive development (Mental Development Index) and behavior (Behavior Rating Scale) assessed with the Bayley Scales of Infant Development at 36 months. Infant attachment style moderated the effects of prenatal adversity on Behavior Rating Scale scores at 36 months. Infant attachment was also significantly associated with a principal component that accounted for 11.9% of the variation in genome-wide DNA methylation. These effects were most apparent when comparing children with a secure versus a disorganized attachment style and most pronounced in females. The availability of paired genetic data revealed that DNA methylation at approximately half of all infant attachment-associated sites was best explained by considering both infant attachment and child genetic variation. This study provides further evidence that infant attachment can buffer some of the negative effects of early adversity on measures of infant behavior. We also highlight the interplay between infant attachment and child genotype in shaping variation in DNA methylation. Such findings provide preliminary evidence for a molecular signature of infant attachment and may help inform attachment-focused early intervention programs.

Animal models of early postnatal mother–infant interactions have highlighted the importance of tactile contact for biobehavioral outcomes via the modification of DNA methylation (DNAm). The role of normative variation in contact in early human development has yet to be explored. In an effort to translate the animal work on tactile contact to humans, we applied a naturalistic daily diary strategy to assess the link between maternal contact with infants and epigenetic signatures in children 4–5 years later, with respect to multiple levels of child-level factors, including genetic variation and infant distress. We first investigated DNAm at four candidate genes: the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), μ-opioid receptor M1 (OPRM1) and oxytocin receptor (OXTR; related to the neurobiology of social bonds), and brain-derived neurotrophic factor (BDNF; involved in postnatal plasticity). Although no candidate gene DNAm sites significantly associated with early postnatal contact, when we next examined DNAm across the genome, differentially methylated regions were identified between high and low contact groups. Using a different application of epigenomic information, we also quantified epigenetic age, and report that for infants who received low contact from caregivers, greater infant distress was associated with younger epigenetic age. These results suggested that early postnatal contact has lasting associations with child biology.

Enteric viruses including norovirus and rotavirus are leading causes of gastroenteritis in Canada. However, only a small number of clinical cases are actually tested for these pathogens leading to systematic underestimation of attributed hospitalizations in administrative databases. The objective of this analysis was to estimate the number of hospitalizations due to norovirus and rotavirus in Canada. Hospitalization records for acute gastroenteritis-associated discharges at all acute-care hospitals in Canada between 2006 and 2011 were analysed. Cause-unspecified gastroenteritis hospitalizations were modelled using age-specific negative binomial models with cause-specified gastroenteritis admissions as predictors. The coefficients from the models were used to estimate the number of norovirus and rotavirus admissions. The total annual hospitalizations for rotavirus were estimated to be between 4500 and 10 000. Total annual hospitalizations for norovirus were estimated to be between 4000 and 11 000. The mean total annual cost associated with these hospitalizations was estimated to be at least $16 million for rotavirus and $21 million for norovirus (all figures in Canadian dollars). This study is the first comprehensive analysis of norovirus and rotavirus hospitalizations in Canada. These estimates provide a more complete assessment of the burden and economic costs of these pathogens to the Canadian healthcare system.

This systematic review–meta-analysis appraises and summarizes all the available research (128 papers) on the zoonotic potential of Mycobacterium avium ssp. paratuberculosis. The latter has been debated for a century due to pathogenic and clinical similarities between Johne's disease in ruminants and Crohn's disease (108 studies) in humans and recently for involvement in other human diseases; human immunodeficiency virus (HIV) infection (2), sarcoidosis (3), diabetes mellitus type 1 (T1DM) (7) and type 2 (3), multiple sclerosis (5) and Hashimoto's thyroiditis (2). Meta-analytical results indicated a significant positive association, consistently across different laboratory methods for Crohn's disease [odds ratio (OR) range 4·26–8·44], T1DM (OR range 2·91–9·95) and multiple sclerosis (OR range 6·5–7·99). The latter two and the thyroiditis hypothesis require further investigation to confirm the association. Meta-regression of Crohn's disease studies using DNA detection methods indicated that choice of primers and sampling frame (e.g. general population vs. hospital-based sample) explained a significant proportion of heterogeneity. Other epidemiological studies demonstrated a lack of association between high-risk occupations and development of Crohn's disease. Due to knowledge gaps in understanding the role of M. paratuberculosis in the development or progression of human disease, the evidence at present is not strong enough to inform the potential public health impact of M. paratuberculosis exposure.

A scoping review was conducted to identify modifiable non-antimicrobial factors to reduce the occurrence of antimicrobial resistance in cattle populations. Searches were developed to retrieve peer-reviewed published studies in animal, human and in vitro microbial populations. Citations were retained when modifiable non-antimicrobial factors or interventions potentially associated with antimicrobial resistance were described. Studies described resistance in five bacterial genera, species or types, and 40 antimicrobials. Modifiable non-antimicrobial factors or interventions ranged widely in type, and the depth of evidence in animal populations was shallow. Specific associations between a factor or intervention with antimicrobial resistance in a population (e.g. associations between organic systems and tetracycline susceptibility in E. coli from cattle) were reported in a maximum of three studies. The identified non-antimicrobial factors or interventions were classified into 16 themes. Most reported associations between the non-antimicrobial modifiable factors or interventions and antimicrobial resistance were not statistically significant (P > 0·05 and a confidence interval including 1), but when significant, the results were not consistent in direction (increase or decrease in antimicrobial resistance) or magnitude. Research is needed to better understand the impacts of promising modifiable factors or interventions on the occurrence of antimicrobial resistance before any recommendations can be offered or adopted.

Food- and waterborne disease is thought to be high in some Canadian Indigenous communities; however, the burden of acute gastrointestinal illness (AGI) is not well understood due to limited availability and quality of surveillance data. This study estimated the burden of community-level self-reported AGI in the Inuit communities of Rigolet, Nunatsiavut, and Iqaluit, Nunavut, Canada. Cross-sectional retrospective surveys captured information on AGI and potential environmental risk factors. Multivariable logistic regression models identified potential AGI risk factors. The annual incidence of AGI ranged from 2·9–3·9 cases/person per year in Rigolet and Iqaluit. In Rigolet, increased spending on obtaining country foods, a homeless person in the house, not visiting a cabin recently, exposure to puppies, and alternative sources of drinking water were associated with increased odds of AGI. In Iqaluit, eating country fish often, exposure to cats, employment status of the person responsible for food preparation, not washing the countertop with soap after preparing meat, a homeless person in the house, and overcrowding were associated with increased odds of AGI. The results highlight the need for systematic data collection to better understand and support previously anecdotal indications of high AGI incidence, as well as insights into unique AGI environmental risk factors in Indigenous populations.

Early life environments interact with genotype to determine stable phenotypic outcomes. Here we examined the influence of a variant in the brain-derived neurotropic factor (BDNF) gene (Val66Met), which underlies synaptic plasticity throughout the central nervous system, on the degree to which antenatal maternal anxiety associated with neonatal DNA methylation. We also examined the association between neonatal DNA methylation and brain substructure volume, as a function of BDNF genotype. Infant, but not maternal, BDNF genotype dramatically influences the association of antenatal anxiety on the epigenome at birth as well as that between the epigenome and neonatal brain structure. There was a greater impact of antenatal maternal anxiety on the DNA methylation of infants with the methionine (Met)/Met compared to both Met/valine (Val) and Val/Val genotypes. There were significantly more cytosine–phosphate–guanine sites where methylation levels covaried with right amygdala volume among Met/Met compared with both Met/Val and Val/Val carriers. In contrast, more cytosine–phosphate–guanine sites covaried with left hippocampus volume in Val/Val infants compared with infants of the Met/Val or Met/Met genotype. Thus, antenatal Maternal Anxiety × BDNF Val66Met Polymorphism interactions at the level of the epigenome are reflected differently in the structure of the amygdala and the hippocampus. These findings suggest that BDNF genotype regulates the sensitivity of the methylome to early environment and that differential susceptibility to specific environmental conditions may be both tissue and function specific.

Laboratory-based surveillance data is essential for monitoring trends in the incidence of enteric disease. Current Canadian human enteric surveillance systems report only confirmed cases of human enteric disease and are often unable to capture the number of negative test results. Data from 9116 hospital stool specimens from the Waterloo Region in Canada, with a mixed urban and rural population of about 500 000 were analysed to investigate the use of stool submission data and its role in reporting bias when determining the incidence of enteric disease. The proportion of stool specimens positive for Campylobacter spp. was highest in the 15–29 years age group, and in the 5–14 years age group for Salmonella spp. and E. coli O157:H7. By contrast, the age-specific incidence rates were highest for all three pathogens in the 0–4 years age group which also had the highest stool submission rate. This suggests that variations in age-specific stool submission rates are influencing current interpretation of surveillance data.