Spatial cluster mapping and environmental modeling in pediatric inflammatory bowel disease

BACKGROUND Geographical(geospatial)clusters have been observed in inflammatory bowel disease(IBD)incidence and linked to environmental determinants of disease,but pediatric spatial patterns in North America are unknown.We hypothesized that we would identify geospatial clusters in the pediatric IBD(PIBD)population of British Columbia(BC),Canada and associate incidence with ethnicity and environmental exposures.AIM To identify PIBD clusters and model how spatial patterns are associated with population ethnicity and environmental exposures.METHODS One thousand one hundred eighty-three patients were included from a BC Children’s Hospital clinical registry who met the criteria of diagnosis with IBD≤age 16.9 from 2001–2016 with a valid postal code on file.A spatial cluster detection routine was used to identify areas with similar incidence.An ecological analysis employed Poisson rate models of IBD,Crohn’s disease(CD),and ulcerative colitis(UC)cases as functions of areal population ethnicity,rurality,average family size and income,average population exposure to green space,air pollution,and vitamin-D weighted ultraviolet light from the Canadian Environmental Health Research Consortium,and pesticide applications.RESULTS Hot spots(high incidence)were identified in Metro Vancouver(IBD,CD,UC),southern Okanagan regions(IBD,CD),and Vancouver Island(CD).Cold spots(low incidence)were identified in Southeastern BC(IBD,CD,UC),Northern BC(IBD,CD),and on BC’s coast(UC).No high incidence hot spots were detected in the densest urban areas.Modeling results were represented as incidence rate ratios(IRR)with 95%CI.Novel risk factors for PIBD included fine particulate matter(PM2.5)pollution(IRR=1.294,CI=1.113-1.507,P<0.001)and agricultural application of petroleum oil to orchards and grapes(IRR=1.135,CI=1.007-1.270,P=0.033).South Asian population(IRR=1.020,CI=1.011-1.028,P<0.001)was a risk factor and Indigenous population(IRR=0.956,CI=0.941-0.971,P<0.001),family size(IRR=0.467,CI=0.268-0.816,P=0.007),and summer ultraviolet(IBD=0.9993,CI=0.9990–0.9996,P<0.001)were protective factors as previously established.Novel risk factors for CD,as for PIBD,included:PM2.5 air pollution(IRR=1.230,CI=1.056-1.435,P=0.008)and agricultural petroleum oil(IRR=1.159,CI=1.002-1.326,P=0.038).Indigenous population(IRR=0.923,CI=0.895–0.951,P<0.001),as previously established,was a protective factor.For UC,rural population(UC IRR=0.990,CI=0.983-0.996,P=0.004)was a protective factor and South Asian population(IRR=1.054,CI=1.030–1.079,P<0.001)a risk factor as previously established.CONCLUSION PIBD spatial clusters were identified and associated with known and novel environmental determinants.The identification of agricultural pesticides and PM2.5 air pollution needs further study to validate these observations.

Perspectives on the role of Pannexin 1 in neural precursor cell biology

We recently reported that targeted deletion of Pannexin 1 in neural precursor cells of the ventricular zone impairs the maintenance of these cells in healthy and stroke-injured brain. Here we frame this exciting new finding in the context of our previous studies on Pannexin 1 in neural precursors as well as the close rela- tionship between Pannexin 1 and purinergic receptors established by other groups. Moreover, we identify important gaps in our understanding of Pannexin 1 in neural precursor cell biology in terms of the under- lying molecular mechanisms and functional/behavioural outcomes.

Consecutive fecal calprotectin measurements for predicting relapse in pediatric Crohn's disease patients

BACKGROUND Asymptomatic children with Crohn's disease(CD) require ongoing monitoring to ensure early recognition of a disease exacerbation.AIM In a cohort of pediatric CD patients, we aimed to assess the utility of serial fecal calprotectin measurements to detect intestinal inflammatory activity and predict disease relapse.METHODS In this prospective longitudinal cohort study, children with CD on infliximab therapy in clinical remission were included. Fecal calprotectin levels were assessed at baseline and at subsequent 2-5 visits. Clinical and biochemical disease activity were assessed using the Pediatric Crohn's Disease Activity Index, Creactive protein and erythrocyte sedimentation rate at baseline and at visits over the following 18 mo.RESULTS 53 children were included and eighteen patients(34%) had a clinical disease relapse during the study. Baseline fecal calprotectin levels were higher in patients that developed symptomatic relapse [median(interquartile range), relapse 723μg/g(283-1758) vs 244 μg/g(61-627), P = 0.02]. Fecal calprotectin levels > 250μg/g demonstrated good predictive accuracy of a clinical flare within 3 mo(area under the receiver operator curve was 0.86, 95% confidence limits 0.781 to 0.937).CONCLUSION Routine fecal calprotectin testing in children with CD in clinical remission is useful to predict relapse. Levels > 250 μg/g are a good predictor of relapse in the following 3 mo. This information is important to guide monitoring standards used in this population.

Exploring salivary biomarkers and swallowing perceptions in Sjogren's syndrome:A case-control feasibility study

Background:The autoimmune disease Sjogren's syndrome(SS)is often characterized by salivary changes that may affect swallowing.No known study has investigated the association between salivary biomarkers and perceptions of swallowing in individuals with SS.Our objectives were to explore:(1)the operational feasibility of investigating saliva volume and composition,along with perceptions of swallowing,in those with and without SS;and(2)the relationship between saliva composition and perceptions of oral dryness,swallowing,and quality of life.Methods:We conducted a prospective,case–control feasibility study,collecting feasibility data(recruitment rate and optimal saliva collection methods)and whole mouth saliva samples(unstimulated and stimulated).We measured total protein content and conducted sialochemical(α-amylase,cortisol,C-reactive protein[CRP],and mucins),sialometric(flow rate),and perceptual(oral dryness and swallowing-related quality of life[SWAL-QOL])assessments.Our exploratory analyses focused on the main and fixed effects.We summarized all data descriptively,comparing:(a)outcomes between groups(t tests or Mann–Whitney U)and(b)salivary and perceptual data across participants(partial least-squares correlation[PLSC]).Results:We enrolled 12(N)participants(6 per group),all providing analyzable saliva.Cases had lower flow rate(p=0.003)and higher total protein,cortisol,and CRP concentrations(p<0.02)than controls.PLSC revealed inverse covariance between sialochemical and SWAL-QOL data across participants.Conclusion:Our study was feasible as designed.We explored novel relationships between salivary outcomes and participant-reported perceptions,distinguishing individuals with and without SS.Our findings support further study of saliva's role in perceptions of swallowing,specifically analytes with lubricative properties.