The Effect of Auditory Distraction on the Useful Field of View in Hearing Impaired Individuals and its implications for driving

This study assessed whether the increased demand of listening in hearing impaired individuals exacerbates the detrimental impact of auditory distraction on a visual task (useful field of view test), relative to normally hearing listeners. Auditory distraction negatively affects this visual task, which is linked with various driving performance outcomes. Hearing impaired and normally hearing participants performed useful field of view testing with and without a simultaneous listening task. They also undertook a cognitive test battery. For all participants, performing the visual and auditory tasks together reduced performance on each respective test. For a number of subtests, hearing impaired participants showed poorer visual task performance, though not to a statistically significant extent. Hearing impaired participants were significantly poorer at a reading span task than normally hearing participants and tended to score lower on the most visually complex subtest of the visual task in the absence of auditory task engagement. Useful field of view performance is negatively affected by auditory distraction, and hearing loss may present further problems, given the reductions in visual and cognitive task performance suggested in this study. Suggestions are made for future work to extend this study, given the practical importance of the findings

Effect of the BRCA2 CTRD domain on RAD51 filaments analyzed by an ensemble of single molecule techniques

Homologous recombination is essential for the preservation of genome stability, thereby preventing cancer. The recombination protein RAD51 drives DNA strand exchange, which requires the assembly, rearrangement and disassembly of a RAD51 filament on DNA, coupled to ATP binding and hydrolysis. This process is facilitated and controlled by recombination mediators and accessory factors. Here, we have employed a range of single molecule techniques to determine the influence of the C-terminal RAD51 interaction domain (CTRD) of the breast cancer tumor suppressor BRCA2 on intrinsic aspects of RAD51-DNA interactions. We show that at high concentration the CTRD entangles RAD51 filaments and reduces RAD51 filament formation in a concentration dependent manner. It does not affect the rate of filament disassembly measured as the loss of fluorescent signal due to intrinsic RAD51 protein dissociation from double-stranded DNA (dsDNA). We conclude that, outside the context of the full-length protein, the CTRD does not reduce RAD51 dissociation kinetics, but instead hinders filament formation on dsDNA. The CTRDs mode of action is most likely sequestration of multiple RAD51 molecules thereby rendering them inactive for filament formation on dsDNA

Trends in absolute socioeconomic inequalities in mortality in Sweden and New Zealand. A 20-year gender perspective

BACKGROUND: Both trends in socioeconomic inequalities in mortality, and cross-country comparisons, may give more information about the causes of health inequalities. We analysed trends in socioeconomic differentials by mortality from early 1980s to late 1990s, comparing Sweden with New Zealand. METHODS: The New Zealand Census Mortality Study (NZCMS) consisting of over 2 million individuals and the Swedish Survey of Living Conditions (ULF) comprising over 100, 000 individuals were used for analyses. Education and household income were used as measures of socioeconomic position (SEP). The slope index of inequality (SII) was calculated to estimate absolute inequalities in mortality. Analyses were based on 3–5 year follow-up and limited to individuals aged 25–77 years. Age standardised mortality rates were calculated using the European population standard. RESULTS: Absolute inequalities in mortality on average over the 1980s and 1990s for both men and women by education were similar in Sweden and New Zealand, but by income were greater in Sweden. Comparing trends in absolute inequalities over the 1980s and 1990s, men's absolute inequalities by education decreased by 66% in Sweden and by 17% in New Zealand (p for trend <0.01 in both countries). Women's absolute inequalities by education decreased by 19% in Sweden (p = 0.03) and by 8% in New Zealand (p = 0.53). Men's absolute inequalities by income decreased by 51% in Sweden (p for trend = 0.06), but increased by 16% in New Zealand (p = 0.13). Women's absolute inequalities by income increased in both countries: 12% in Sweden (p = 0.03) and 21% in New Zealand (p = 0.04). CONCLUSION: Trends in socioeconomic inequalities in mortality were clearly most favourable for men in Sweden. Trends also seemed to be more favourable for men than women in New Zealand. Assuming the trends in male inequalities in Sweden were not a statistical chance finding, it is not clear what the substantive reason(s) was for the pronounced decrease. Further gender comparisons are required

The Epistatic Relationship between BRCA2 and the Other RAD51 Mediators in Homologous Recombination

RAD51 recombinase polymerizes at the site of double-strand breaks (DSBs) where it performs DSB repair. The loss of RAD51 causes extensive chromosomal breaks, leading to apoptosis. The polymerization of RAD51 is regulated by a number of RAD51 mediators, such as BRCA1, BRCA2, RAD52, SFR1, SWS1, and the five RAD51 paralogs, including XRCC3. We here show that brca2-null mutant cells were able to proliferate, indicating that RAD51 can perform DSB repair in the absence of BRCA2. We disrupted the BRCA1, RAD52, SFR1, SWS1, and XRCC3 genes in the brca2-null cells. All the resulting double-mutant cells displayed a phenotype that was very similar to that of the brca2-null cells. We suggest that BRCA2 might thus serve as a platform to recruit various RAD51 mediators at the appropriate position at the DNA–damage site

BRIT1/MCPH1 Is Essential for Mitotic and Meiotic Recombination DNA Repair and Maintaining Genomic Stability in Mice

BRIT1 protein (also known as MCPH1) contains 3 BRCT domains which are conserved in BRCA1, BRCA2, and other important molecules involved in DNA damage signaling, DNA repair, and tumor suppression. BRIT1 mutations or aberrant expression are found in primary microcephaly patients as well as in cancer patients. Recent in vitro studies suggest that BRIT1/MCPH1 functions as a novel key regulator in the DNA damage response pathways. To investigate its physiological role and dissect the underlying mechanisms, we generated BRIT1−/− mice and identified its essential roles in mitotic and meiotic recombination DNA repair and in maintaining genomic stability. Both BRIT1−/− mice and mouse embryonic fibroblasts (MEFs) were hypersensitive to γ-irradiation. BRIT1−/− MEFs and T lymphocytes exhibited severe chromatid breaks and reduced RAD51 foci formation after irradiation. Notably, BRIT1−/− mice were infertile and meiotic homologous recombination was impaired. BRIT1-deficient spermatocytes exhibited a failure of chromosomal synapsis, and meiosis was arrested at late zygotene of prophase I accompanied by apoptosis. In mutant spermatocytes, DNA double-strand breaks (DSBs) were formed, but localization of RAD51 or BRCA2 to meiotic chromosomes was severely impaired. In addition, we found that BRIT1 could bind to RAD51/BRCA2 complexes and that, in the absence of BRIT1, recruitment of RAD51 and BRCA2 to chromatin was reduced while their protein levels were not altered, indicating that BRIT1 is involved in mediating recruitment of RAD51/BRCA2 to the damage site. Collectively, our BRIT1-null mouse model demonstrates that BRIT1 is essential for maintaining genomic stability in vivo to protect the hosts from both programmed and irradiation-induced DNA damages, and its depletion causes a failure in both mitotic and meiotic recombination DNA repair via impairing RAD51/BRCA2's function and as a result leads to infertility and genomic instability in mice

Does transition from an unstable labour market position to permanent employment protect mental health? Results from a 14-year follow-up of school-leavers

<p>Abstract</p> <p>Background</p> <p>Having secure employment, in contrast to being unemployed, is regarded as an important determinant of health. Research and theories about the negative health consequences of unemployment indicated that transition from unemployment to a paid job could lead to improved health. The objective of this study was to test the hypothesis that obtaining permanent employment after being in an unstable labour market position protects mental health.</p> <p>Methods</p> <p>A 14-year follow-up of all graduates from compulsory school in an industrial town in northern Sweden was performed at ages 16, 18, 21 and 30 years. Complete data on the cohort were collected for 1044 individuals with the aid of a comprehensive questionnaire. The response rate was 96.4%. The health measurement used in this study was the psychological symptoms analysed by multivariate logistic regression. Those who obtained permanent employment were the focus of the analysis. This group consisted of people who were in an unstable labour market position for a year or more between the ages of 25 and 29, and who had acquired a permanent job one year before and at the time of the investigation.</p> <p>Results</p> <p>After controlling for gender as well as for an indicator of health-related selection, possible confounders and mediators, an association was found between the lower probability of psychological symptoms and obtaining permanent employment (OR = 0.35, 95% CI 0.19–0.63) as well as having permanent employment (OR = 0.22, 95% CI 0.10–0.51).</p> <p>Conclusion</p> <p>Our findings suggest that transition from an unstable labour market position to permanent employment could be health-promoting, even after controlling for possible confounders and mediators, as well as for an indicator of health-related selection. However, as there are few studies in the field, there is a need for more longitudinal studies in order to further analyse the relationship and to examine possible explanations. The policy implication of our study is that the transformation of unstable labour market positions into permanent employment could contribute to better public health.</p

Effect of a primary health-care-based controlled trial for cardiorespiratory fitness in refugee women

BACKGROUND: Refugee women have a high risk of coronary heart disease with low physical activity as one possible mediator. Furthermore, cultural and environmental barriers to increasing physical activity have been demonstrated. The aim of the study was to evaluate the combined effect of an approximate 6-month primary health care- and community-based exercise intervention versus an individual written prescription for exercise on objectively assessed cardiorespiratory fitness in low-active refugee women. METHODS: A controlled clinical trial, named "Support for Increased Physical Activity", was executed among 243 refugee women recruited between November 2006 and April 2008 from two deprived geographic areas in southern Stockholm, Sweden. One geographic area provided the intervention group and the other area the control group. The control group was on a higher activity level at both baseline and follow-up, which was taken into consideration in the analysis by applying statistical models that accounted for this. Relative aerobic capacity and fitness level were assessed as the two main outcome measures. RESULTS: The intervention group increased their relative aerobic capacity and the percentage with an acceptable fitness level (relative aerobic capacity > 23 O2 mlxkgxmin-1) to a greater extent than the control group between baseline and the 6-month follow-up, after adjusting for possible confounders (P = 0.020). CONCLUSIONS: A combined primary health-care and community-based exercise programme (involving non-profit organizations) can be an effective strategy to increase cardiorespiratory fitness among low-active refugee women. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT00747942

Lympho-vascular invasion in BRCA related breast cancer compared to sporadic controls

<p>Abstract</p> <p>Background</p> <p>Germline mutations in the BRCA1 gene predispose to the development of breast cancer, exhibiting a specific histological phenotype. Identification of possible hallmarks of these tumors is important for selecting patients for genetic screening and provides inside in carcinogenetic pathways.</p> <p>Since BRCA1-associated breast cancers have pushing borders that prevent them from easily reaching vessels and are often of the medullary (like) type that is known to have a low rate of lympho-vascular invasion (LVI), we hypothesized that absence of LVI could characterize BRCA1 related breast cancer.</p> <p>Methods</p> <p>A population of 68 BRCA1 related invasive breast cancers was evaluated for LVI by an experienced breast pathologist blinded to mutation status, and compared to a control group matched for age, grade and tumor type.</p> <p>Results</p> <p>LVI was present in 25.0% of BRCA1 related cases, compared to 20.6% of controls (P = 0.54, OR = 1.29, CI 0.58-2.78).</p> <p>Conclusion</p> <p>LVI is frequent in BRCA1 germline mutation related breast cancers, but seems to occur as often in sporadic controls matched for age, grade and tumor type. Apparently, these hereditary cancers find their way to the blood and lymph vessels despite their well demarcation and often medullary differentiation.</p