Toenail speciation biomarkers in arsenic-related disease: a feasibility study for investigating the association between arsenic exposure and chronic disease.

Long-term exposure to environmental arsenic has been associated with many chronic diseases, including several cancers, and diabetes. Urinary studies have implicated arsenic speciation as an important risk factor, however, such associations have not been replicated using toenail samples: a relatively new biosample for estimating long-term internal dose-exposure to arsenic. Despite having several advantages over conventional biosamples such as ease of collection and storage, standard methods for arsenic speciation analysis in toenails have not yet been established. The primary objectives of this study were to 1) establish an analytical method for arsenic speciation analysis in toenails, 2) describe preliminary arsenic speciation profiles of toenail samples from individuals with skin, lung, bladder, and kidney cancer, type II diabetes, and no known disease, and 3) determine if these speciation patterns differ between disease groups to inform the feasibility of subsequent research. A small cross-sectional feasibility study was carried out using 60 toenail samples and baseline questionnaire data from the Atlantic Partnership for Tomorrow's Health (Atlantic PATH) study. Arsenic speciation profiles were determined using high performance liquid chromatography (HPLC) paired with inductively coupled plasma-mass spectrometry (ICP-MS). While no differences in total arsenic were found, arsenic speciation profiles were significantly different between certain cancer groups and the reference group with no known disease. Specifically, the percentage of monomethylarsonic acid (%MMA) was found to be significantly higher in the toenails of individuals with lung cancer and kidney cancer, compared to healthy individuals with similar total arsenic exposure. To the best of our knowledge, this is the first study to describe arsenic speciation patterns in individuals with several arsenic-related diseases using toenails: a convenient, non-invasive, biobankable sample capable of longer-term exposure estimation than conventional biosamples. These preliminary data provide evidence that toenail arsenic speciation patterns differ between groups with arsenic-related disease, and those with no known disease. Toenail arsenic speciation analysis is feasible and could potentially have important implications for research on arsenic-related diseases. Further investigation is warranted and would benefit from including detailed arsenic exposure data to explore the observed heterogeneity in arsenic speciation profiles.

The Long-Term Pelvic Floor Health Outcomes of Women After Childbirth: The Influence of Labour in the First Pregnancy.

OBJECTIVE: To estimate the influence of labour and pregnancy factors on long-term pelvic floor health outcomes. METHODS: This population-based cohort study was conducted using linkage between the Nova Scotia Atlee Perinatal Database, the Medical Services Insurance Database, and the Canadian Institute for Health Information's Discharge Abstract Database from 1988 to 2006; this allowed for the evaluation of patient utilization of care providers for pelvic floor disorders and captured conservative and surgical interventions. We compared rates of urinary and anal incontinence, pelvic organ prolapse, and fistula disorders in women undergoing Caesarean section (CS) without labour and women undergoing labour with any method of delivery. Multivariate logistic regression and survival (time-to-event) analyses were performed. RESULTS: Absolute risks for the selected pelvic floor health outcomes were low, regardless of whether labour was experienced in the first pregnancy. Women with one or more deliveries who had a CS without labour in their first pregnancy had reduced risks for all pelvic floor health outcomes, except fistula formation, and they were also less likely to develop these outcomes during the study period. CONCLUSION: Women undergoing obstetrically indicated CS without labour in their first delivery may have reduced risks of pelvic floor health disorders, even after multiple deliveries. These findings contribute important information for health care providers when counselling women and their families who are weighing the risk of long-term pelvic floor disorders against the benefits of spontaneous vaginal delivery.

Factors affecting the age at diagnosis of autism spectrum disorders in Nova Scotia, Canada.

While early diagnosis of autism spectrum disorders (ASD) is essential for ensuring timely access to early intervention services, there is limited existing literature investigating factors that delay this diagnosis. This population-based cohort study explored the age at which children in Nova Scotia, Canada, are diagnosed with ASDs and the factors associated with this age. Children diagnosed with an ASD between January 1992 and December 2005 were identified from a cohort of live births in the province between 1990 and 2002. Demographic and clinical variables were extracted from population-based perinatal and administrative health databases and evaluated as predictors of age at ASD diagnosis. Of 122,759 live births, 884 cases of ASDs were identified during the study period. The median age at diagnosis within the cohort was 4.6 years. In adjusted linear regression analysis, a one year increase in maternal age at delivery was associated with a 0.06 decrease in age at ASD diagnosis (p= .0007). Children who were residents of Halifax County received their diagnoses 0.52 years later than residents of other counties (p= .0054). A diagnosis of attention-deficit/hyperactivity disorder (ADHD) was associated with a 1.29-year increase in age at diagnosis (p< .0001). These results suggest that potential exists for improving early detection of ASDs in the province. Future research in this field has the potential to contribute to our understanding of the causal pathways linking the demographic and clinical variables we have identified and the age at diagnosis of ASDs.

Far from ideal: weight perception, weight control, and associated risky behaviour of adolescent girls in Nova Scotia.

OBJECTIVE: To examine the prevalence of weight-related concerns, unhealthy weight-control behaviour, and associated risky behaviour among adolescent girls, and to ascertain whether these girls had discussed a healthy weight with their physicians. DESIGN: Anonymous, self-report, cross-sectional survey. SETTING: Four high schools in rural Nova Scotia. PARTICIPANTS: Adolescent girls in grades 10 to 12. MAIN OUTCOME MEASURES: Weight perception, prevalence of weight-control behaviour, associations between weight perception and risky behaviour, associations between disordered eating behaviour and other risky behaviour. RESULTS: Overall response rate was 76%. Half the 1133 participants saw themselves as not being the "right" weight; 60% were trying to lose weight. During the past 30 days, 16% of the girls were attempting to control or lose weight and had engaged in disordered eating behaviour. In univariate analysis, perception of being either overweight or underweight was significantly associated with suicidal thoughts, suicide planning, and risk of depression. In multivariate analysis, positive associations were found between disordered eating behaviour and suicidal thoughts (odds ratio [OR] 4.2, 95% confidence interval [CI] 2.6 to 6.7), suicide planning (OR 2.9, 95% CI 1.7 to 4.7), suicide attempts (OR 3.4, 95% CI 1.8 to 6.6), and ever having had vaginal intercourse (OR 1.6, 95% CI 1.1 to 2.5). Only 22% of respondents had spoken with a doctor about a healthy weight. CONCLUSION: Weight concerns are prevalent among adolescent girls in Nova Scotia. Many of them, especially those who see themselves as overweight or underweight, engage in unhealthy weight-control methods. Perceived underweight and overweight and disordered eating behaviour have strong associations with depression and self-harming behaviour. Few participants had discussed a healthy weight with a physician. Health professionals should be aware of the associations between weight perception and disordered eating behaviour and other risky behaviour.

Improved prediction of early-onset coronary artery disease using APOE epsilon4, BChE-K, PPARgamma2 Pro12 and ENOS T-786C in a polygenic model.

OBJECTIVES: Coronary artery disease (CAD) is often polygenic due to multiple mutations that contribute small effects to susceptibility. Since most prior studies only evaluated the contribution of single candidate genes, we therefore looked at a combination of genes in predicting early-onset CAD [apolipoprotein E (APOE) epsilon4, butyrylcholinesterase (BChE) K, peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala and endothelial nitric oxide synthase (ENOS) T-786C]. DESIGN AND METHODS: We examined the frequencies, individually and in combination, of all four alleles among patients with early-onset CAD (n = 150; <50 years), late-onset CAD (n = 150; >65 years) and healthy controls (n = 150, age range 47-93 years). Differences in the proportion of subjects in each group with the given gene combination were assessed and likelihood ratios (LR) were calculated using logistic regression to combine the results of multiple genes. RESULTS: Early-onset CAD patients had increased, but non-significant, frequencies of PPARgamma2 Pro12/Pro12 (P = 0.39) and ENOS T-786C (P = 0.72), while BChE-K was only significantly higher in early-onset CAD patients compared to controls (P = 0.03). There were significantly more APOE epsilon4 alleles alone (P = 0.02) or in combination with BChE-K (P = 0.02) among early-onset CAD patients compared to late-onset CAD ones or controls. When combined, there was a higher prevalence of all four alleles in early-onset CAD (early-onset CAD patients: 10.7%, late-onset CAD patients: 3.3% and controls: 2.7%, P = 0.01). LR for early-onset CAD for a single allele was relatively small (1.08 for PPARgamma2 to 1.70 for APOE epsilon4). This increased to 2.78 (1.44-5.37) when combining all four alleles, therefore increasing the pre-test probability of CAD from 5% to a post-test probability of 12.7%. CONCLUSIONS: While any single mutation causes only a mildly increased LR (none > 1.7), in combination, the likelihood of early-onset CAD increased to 2.78 with four mutations. The genetics of early-onset CAD appear to be multifactorial, requiring polygenic models to elucidate risk.