The Suitability of Questionnaires for Exploring Relations of Dietary Behavior and Tooth Wear

Tooth wear is a relevant oral health problem, especially at a young age. Although ongoing acid exposures may contribute to tooth wear, the role of acidic dietary components in this context remains unclear. To date, in tooth wear studies, dietary behavior has been assessed using traditional questionnaires, but the suitability of this approach has not been investigated so far. In our longitudinal study, we followed 91 participants (21.0 ± 2.2 years) over a period of 1 year (373 ± 19 days) and monitored tooth wear with an intraoral scanner. At baseline (T0) and at the end (T1), we assessed dietary behavior with questionnaires asking about the consumption frequencies of acidic dietary components and the acid taste preferences. Complete data were available from 80 subjects. The consumption frequencies of T0 and T1 correlated weakly to moderately. Taste preferences seem to be a more consistent measure, but there was predominantly no significant correlation with the corresponding consumption frequencies. None of the dietary parameters showed a significant relation with tooth wear. The suitability of dietary questionnaires to assess tooth-relevant dietary behavior seems to be limited.     

The Second Canadian Symposium on Hepatitis C Virus: A call to action

In Canada, hepatitis C virus (HCV) infection results in considerable morbidity, mortality and health-related costs. Within the next three to 10 years, it is expected that tolerable, short-duration (12 to 24 weeks) therapies capable of curing >90% of those who undergo treatment will be approved. Given that most of those already infected are aging and at risk for progressive liver disease, building research-based interdisciplinary prevention, care and treatment capacity is an urgent priority. In an effort to increase the dissemination of knowledge in Canada in this rapidly advancing field, the National CIHR Research Training Program in Hepatitis C (NCRTP-HepC) established an annual interdisciplinary Canadian Symposium on Hepatitis C Virus. The first symposium was held in Montreal, Quebec, in 2012, and the second symposium was held in Victoria, British Columbia, in 2013. The current article presents highlights from the 2013 meeting. It summarizes recent advances in HCV research in Canada and internationally, and presents the consensus of the meeting participants that Canada would benefit from having its own national HCV strategy to identify critical gaps in policies and programs to more effectively address the challenges of expanding HCV screening and treatment.     

Risk-Based Chemical Ranking and Generating a Prioritized Human Exposome Database

Background: Due to the ubiquitous use of chemicals in modern society, humans are increasingly exposed to thousands of chemicals that contribute to a major portion of the human exposome. Should a comprehensive and risk-based human exposome database be created, it would be conducive to the rapid progress of human exposomics research. In addition, once a xenobiotic is biotransformed with distinct half-lives upon exposure, monitoring the parent compounds alone may not reflect the actual human exposure. To address these questions, a comprehensive and risk-prioritized human exposome database is needed.Objectives: Our objective was to set up a comprehensive risk-prioritized human exposome database including physicochemical properties as well as risk prediction and develop a graphical user interface (GUI) that has the ability to conduct searches for content associated with chemicals in our database.Methods: We built a comprehensive risk-prioritized human exposome database by text mining and database fusion. Subsequently, chemicals were prioritized by integrating exposure level obtained from the Systematic Empirical Evaluation of Models with toxicity data predicted by the Toxicity Estimation Software Tool and the Toxicological Priority Index calculated from the ToxCast database. The biotransformation half-lives (HLBs) of all the chemicals were assessed using the Iterative Fragment Selection approach and biotransformation products were predicted using the previously developed BioTransformer machine-learning method.Results: We compiled a human exposome database of >20,000 chemicals, prioritized 13,441 chemicals based on probabilistic hazard quotient and 7,770 chemicals based on risk index, and provided a predicted biotransformation metabolite database of >95,000 metabolites. In addition, a user-interactive Java software (Oracle)-based search GUI was generated to enable open access to this new resource.Discussion: Our database can be used to guide chemical management and enhance scientific understanding to rapidly and effectively prioritize chemicals for comprehensive biomonitoring in epidemiological investigations. https://doi.org/10.1289/EHP7722     

Application of whole‐brain CBV‐weighted fMRI to a cognitive stimulation paradigm: Robust activation detection in a stroop task experiment using 3D GRASE VASO

Brain activation studies generally utilize blood oxygenation level dependent (BOLD) contrast, most commonly measured using the gradient‐echo echo‐planar imaging (EPI) technique. BOLD contrast arises from regional changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and the local metabolic rate of oxygen consumption. An alternative to BOLD is the detection of activation through direct measurement of these parameters. A noninvasive approach to measure activation‐related CBV changes is the vascular space occupancy (VASO) method, which exploits blood as an endogenous contrast agent by selectively nulling the magnetization of the water spins in the blood. Using a recently developed multislice variant of VASO that enables single‐shot whole‐brain coverage by virtue of a three‐dimensional GRASE readout, we here present the first application of VASO to an fMRI study with a whole‐brain cognitive task. Within acceptable measurement times (～12 minutes), brain activation during a Stroop color‐word matching task could be detected reliably both on the group (N = 12) and single subject level, as evident from a qualitative comparison with separately acquired BOLD data and literature reports. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

High Skp2 expression characterizes high-risk neuroblastomas independent of MYCN status.

PURPOSE: Amplified MYCN oncogene defines a subgroup of neuroblastomas with poor outcome. However, a substantial number of MYCN single-copy neuroblastomas exhibits an aggressive phenotype similar to that of MYCN-amplified neuroblastomas even in the absence of high MYCN mRNA and/or protein levels. EXPERIMENTAL DESIGN: To identify shared molecular mechanisms that mediate the aggressive phenotype in MYCN-amplified and single-copy high-risk neuroblastomas, we defined genetic programs evoked by ectopically expressed MYCN in vitro and analyzed them in high-risk versus low-risk neuroblastoma tumors (n = 49) using cDNA microarrays. Candidate gene expression was validated in a separate cohort of 117 patients using quantitative PCR, and protein expression was analyzed in neuroblastoma tumors by immunoblotting and immunohistochemistry. RESULTS: We identified a genetic signature characterized by a subset of MYCN/MYC and E2F targets, including Skp2, encoding the F-box protein of the SCF(Skp2) E3-ligase, to be highly expressed in high-risk neuroblastomas independent of amplified MYCN. We validated the findings for Skp2 and analyzed its expression in relation to MYCN and E2F-1 expression in a separate cohort (n = 117) using quantitative PCR. High Skp2 expression proved to be a highly significant marker of dire prognosis independent of both MYCN status and disease stage, on the basis of multivariate analysis of event-free survival (hazard ratio, 3.54; 95% confidence interval, 1.56-8.00; P = 0.002). Skp2 protein expression was inversely correlated with expression of p27, the primary target of the SCF(Skp2) E3-ligase, in neuroblastoma tumors. CONCLUSION: Skp2 may have a key role in the progression of neuroblastomas and should make an attractive target for therapeutic approaches.     

Translating expression profiling into a clinically feasible test to predict neuroblastoma outcome.

PURPOSE: To assess the feasibility of predicting neuroblastoma outcome using highly parallel quantitative real-time PCR data. EXPERIMENTAL DESIGN: We generated expression profiles of 63 neuroblastoma patients, 47 of which were analyzed by both Affymetrix U95A microarrays and highly parallel real-time PCR on microfluidic cards (MFC; Applied Biosystems). Top-ranked genes discriminating patients with event-free survival or relapse according to high-level analysis of Affymetrix chip data, as well as known neuroblastoma marker genes (MYCN and NTRK1/TrkA), were quantified simultaneously by real-time PCR. Analysis of PCR data was accomplished using high-level bioinformatics methods including prediction analysis of microarray, significance analysis of microarray, and Computerized Affected Sibling Pair Analyzer and Reporter. RESULTS: Internal validation of the MFC method proved it highly reproducible. Correlation of MFC and chip expression data varied markedly for some genes. Outcome prediction using prediction analysis of microarray on real-time PCR data resulted in 80% accuracy, which is comparable to results obtained using the Affymetrix platform. Real-time PCR data were useful for risk assessment of relapsing neuroblastoma (P = 0.0006, log-rank test) when Computerized Affected Sibling Pair Analyzer and Reporter analysis was applied. CONCLUSIONS: These data suggest that multiplex real-time PCR might be a promising approach to reduce the complexity of information obtained from whole-genome array experiments. It could provide a more convenient and less expensive tool for routine application in a clinical setting.     

Substitution therapy for heroin addiction

Substitution treatment for heroin addiction, defined here as maintenance prescribing of opioid agonist drugs to opioid dependent subjects, has increased in the last decade. The recent history of substitution treatment in five countries--Canada, the U.K., Australia, Israel, and France--is reviewed. In all five countries, the critical issues around substitution treatment are similar. The first key issue concerns the balance between making treatment accessible and attractive, and minimizing diversion to the black market. The second issue concerns the role of primary health care in delivering MMT. In general, there has been increasing involvement of primary health care, with training and support for practitioners. However, there remains uncertainty and official ambivalence over whether treatment should be restricted to specialist clinics and practitioners, or available through primary care. Most importantly, underlying these issues is the problem of stigma being associated with both addiction, and with substitution treatment. The underlying problem that treatment is often at odds with community values places enormous strains on substitution treatment, and makes the treatment system vulnerable to shifting community support and abrupt, politically-driven changes in policy.