MRI and Neuropsychological Correlates of Carbon Monoxide Exposure: A Case Report

A 45-year-old woman experienced long-term, chronic exposure to carbon monoxide in the restaurant kitchen where she was employed as a cook. After returning to the restaurant after 5 days off work, she noticed that her symptoms returned immediately; she then aired out the room and called the gas company. Approximately 6 hr after a leak was detected, the patient went to the hospital, where her carboxyhemoglobin was found to be within normal limits and results of a neurologic examination were described as normal. Based on her symptoms, the patient believed she had been exposed to CO for at least 1 year before the leak was discovered. Initially, she experienced flu-like symptoms, which eventually resolved. At the time of her first neuropsychological evaluation (17 months after the exposure was identified), her persisting complaints included difficulties in reading, writing, speaking and word retrieval. The test results were consistent with secondary frontal lobe dysfunction associated with subcortical disorders such as those seen after CO exposure. Results of a subsequent neuropsychological examination (29 months postexposure) showed slight improvement in performance, but her performance was still consistent with mild frontal/subcortical dysfunction. Although the initial screening of a brain magnetic resonance image (MRI) performed 15 months after the exposure was interpreted as being within normal limits, two subsequent blind reviews of the same scans identified multiple bilateral lesions in the basal ganglia, which were consistent with chronic CO exposure. We present this case as an example of the utility of MRI and neuropsychological examinations in detecting central nervous system dysfunction secondary to CO exposure

Self-regulatory coping among community dwelling older adults with multiple chronic conditions

ObjectivesMany older adults with multiple chronic conditions (MCC) frequently experience hospitalizations, functional limitations, and poor quality of life. Outcomes may be improved by promoting self-regulation, which may individuals respond to health threats and manage their health conditions. The aim of this study was to describe self-regulatory coping among older adults with MCC.MethodsA qualitative descriptive study using semi-structured interviews and content analysis and guided by the Common-Sense Self-Regulation Model. Seventeen community-dwelling older adults with two or more chronic conditions participated in our study.ResultsThree themes were developed from the analysis: (1) “I don’t think about it unless something happens": coping in the absence of a health event, (2) "doing what I am supposed to do”: coping during a health event, and (3) “How do I know if what I did works?”: appraisal of coping success.DiscussionSelf-regulatory coping was influenced by individual beliefs and experiences (illness representations), context, self-efficacy and availability of support and resources to cope with MCC. These findings suggest implications for clinical practice and future self-regulation interventions for older adults with MCC

The promoter from SlREO, a highly-expressed, root-specific Solanum lycopersicum gene, directs expression to cortex of mature roots

Root-specific promoters are valuable tools for targeting transgene expression, but many of those already described have limitations to their general applicability. We present the expression characteristics of SlREO, a novel gene isolated from tomato (Solanum lycopersicum L.). This gene was highly expressed in roots but had a very low level of expression in aerial plant organs. A 2.4-kb region representing the SlREO promoter sequence was cloned upstream of the uidA GUS reporter gene and shown to direct expression in the root cortex. In mature, glasshouse-grown plants this strict root specificity was maintained. Furthermore, promoter activity was unaffected by dehydration or wounding stress but was somewhat suppressed by exposure to NaCl, salicylic acid and jasmonic acid. The predicted protein sequence of SlREO contains a domain found in enzymes of the 2-oxoglutarate and Fe(II)-dependent dioxygenase superfamily. The novel SlREO promoter has properties ideal for applications requiring strong and specific gene expression in the bulk of tomato root tissue growing in soil, and is also likely to be useful in other Solanaceous crop

The landscape of gifted and talented education in England and Wales: How are teachers implementing policy?

This is an Author's Accepted Manuscript of an article published in Research Papers in Education, 27(2), 167-186, 2012, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/02671522.2010.509514.This paper explores the evidence relating to how primary schools are responding to the ‘gifted and talented’ initiative in England and Wales. A questionnaire survey which invited both closed and open-ended responses was carried out with a national sample of primary schools. The survey indicated an increasing proportion of coordinators, compared with a survey carried out in 1996, were identifying their gifted and talented children as well as having associated school policies. However, the survey also highlighted a number of issues which need addressing if the initiative is to achieve its objective of providing the best possible educational opportunities for children. For example, it was found that a significant number of practitioners were not aware of the existence of the National Quality Standards for gifted and talented education, provided by the UK government in 2007, and the subject-specific criteria provided by the UK’s Curriculum Authority for identification and provision have been largely ignored. The process of identifying children to be placed on the ‘gifted and talented’ register seems haphazard and based on pragmatic reasons. Analysis of teachers’ responses also revealed a range of views and theoretical positioning held by them, which have implications for classroom practice. As the ‘gifted and talented’ initiative in the UK is entering a second decade, and yet more significant changes in policy are introduced, pertinent questions need to be raised and given consideration

Cholesterol and the risk of grade-specific prostate cancer incidence: evidence from two large prospective cohort studies with up to 37 years' follow up

<b>Background</b> High cholesterol may be a modifiable risk factor for prostate cancer but results have been inconsistent and subject to potential "reverse causality" where undetected disease modifies cholesterol prior to diagnosis.<p></p> <b>Methods</b> We conducted a prospective cohort study of 12,926 men who were enrolled in the Midspan studies between 1970 and 1976 and followed up to 31st December 2007. We used Cox-Proportional Hazards Models to evaluate the association between baseline plasma cholesterol and Gleason grade-specific prostate cancer incidence. We excluded cancers detected within at least 5 years of cholesterol assay.<p></p> <b>Results</b> 650 men developed prostate cancer in up to 37 years' follow-up. Baseline plasma cholesterol was positively associated with hazard of high grade (Gleason score[greater than or equal to]8) prostate cancer incidence (n=119). The association was greatest among men in the 4th highest quintile for cholesterol, 6.1 to <6.69 mmol/l, Hazard Ratio 2.28, 95% CI 1.27 to 4.10, compared with the baseline of <5.05 mmol/l. This association remained significant after adjustment for body mass index, smoking and socioeconomic status.<p></p> <b>Conclusions</b> Men with higher cholesterol are at greater risk of developing high-grade prostate cancer but not overall risk of prostate cancer. Interventions to minimise metabolic risk factors may have a role in reducing incidence of aggressive prostate cancer

Application of a new approach methodology (NAM)-based strategy for genotoxicity assessment of data-poor compounds

The conventional battery for genotoxicity testing is not well suited to assessing the large number of chemicals needing evaluation. Traditional in vitro tests lack throughput, provide little mechanistic information, and have poor specificity in predicting in vivo genotoxicity. New Approach Methodologies (NAMs) aim to accelerate the pace of hazard assessment and reduce reliance on in vivo tests that are time-consuming and resource-intensive. As such, high-throughput transcriptomic and flow cytometry-based assays have been developed for modernized in vitro genotoxicity assessment. This includes: the TGx-DDI transcriptomic biomarker (i.e., 64-gene expression signature to identify DNA damage-inducing (DDI) substances), the MicroFlow® assay (i.e., a flow cytometry-based micronucleus (MN) test), and the MultiFlow® assay (i.e., a multiplexed flow cytometry-based reporter assay that yields mode of action (MoA) information). The objective of this study was to investigate the utility of the TGx-DDI transcriptomic biomarker, multiplexed with the MicroFlow® and MultiFlow® assays, as an integrated NAM-based testing strategy for screening data-poor compounds prioritized by Health Canada’s New Substances Assessment and Control Bureau. Human lymphoblastoid TK6 cells were exposed to 3 control and 10 data-poor substances, using a 6-point concentration range. Gene expression profiling was conducted using the targeted TempO-Seq™ assay, and the TGx-DDI classifier was applied to the dataset. Classifications were compared with those based on the MicroFlow® and MultiFlow® assays. Benchmark Concentration (BMC) modeling was used for potency ranking. The results of the integrated hazard calls indicate that five of the data-poor compounds were genotoxic in vitro, causing DNA damage via a clastogenic MoA, and one via a pan-genotoxic MoA. Two compounds were likely irrelevant positives in the MN test; two are considered possibly genotoxic causing DNA damage via an ambiguous MoA. BMC modeling revealed nearly identical potency rankings for each assay. This ranking was maintained when all endpoint BMCs were converted into a single score using the Toxicological Prioritization (ToxPi) approach. Overall, this study contributes to the establishment of a modernized approach for effective genotoxicity assessment and chemical prioritization for further regulatory scrutiny. We conclude that the integration of TGx-DDI, MicroFlow®, and MultiFlow® endpoints is an effective NAM-based strategy for genotoxicity assessment of data-poor compounds

Asthma-associated genetic variants induce IL33 differential expression through an enhancer-blocking regulatory region

Genome-wide association studies (GWAS) have implicated the IL33 locus in asthma, but the underlying mechanisms remain unclear. Here, we identify a 5 kb region within the GWAS-defined segment that acts as an enhancer-blocking element in vivo and in vitro. Chromatin conformation capture showed that this 5 kb region loops to the IL33 promoter, potentially regulating its expression. We show that the asthma-associated single nucleotide polymorphism (SNP) rs1888909, located within the 5 kb region, is associated with IL33 gene expression in human airway epithelial cells and IL-33 protein expression in human plasma, potentially through differential binding of OCT-1 (POU2F1) to the asthma-risk allele. Our data demonstrate that asthma-associated variants at the IL33 locus mediate allele-specific regulatory activity and IL33 expression, providing a mechanism through which a regulatory SNP contributes to genetic risk of asthma.This work was supported by NIH grants R01 HL118758, R01 HL128075, R01 HL119577, R01 HL085197, U19 AI095230, UG3 OD023282 and UM1 AI114271