Citations

Objectives Growing evidence suggests that gender-blind assessment of exposure may introduce exposure misclassification, but few studies have characterised gender differences across occupations and industries. We pooled control responses to job-specific, industry-specific and exposure-specific questionnaires (modules) that asked detailed questions about work activities from three US population-based case–control studies to examine gender differences in work tasks and their frequencies. Methods We calculated the ratio of female-to-male controls that completed each module. For four job modules (assembly worker, machinist, health professional, janitor/cleaner) and for subgroups of jobs that completed those modules, we evaluated gender differences in task prevalence and frequency using χ2 and Mann–Whitney U tests, respectively. Results The 1360 female and 2245 male controls reported 6033 and 12 083 jobs, respectively. Gender differences in female:male module completion ratios were observed for 39 of 45 modules completed by ≥20 controls. Gender differences in task prevalence varied in direction and magnitude. For example, female janitors were significantly more likely to polish furniture (79% vs 44%), while male janitors were more likely to strip floors (73% vs 50%). Women usually reported more time spent on tasks than men. For example, the median hours per week spent degreasing for production workers in product manufacturing industries was 6.3 for women and 3.0 for men. Conclusions Observed gender differences may reflect actual differences in tasks performed or differences in recall, reporting or perception, all of which contribute to exposure misclassification and impact relative risk estimates. Our findings reinforce the need to capture subject-specific information on work tasks.

AbstractGene regulation resulting from glucocorticoid receptor and glucocorticoid response element interactions is a hallmark feature of stress response signaling. Imbalanced glucocorticoid production and glucocorticoid receptor activity have been linked to socioeconomically crippling neuropsychiatric disorders, and accordingly there is a need to developin vivomodels to help understand disease progression and management. Therefore, we developed the transgenicSR4Gzebrafish reporter line with six glucocorticoid response elements used to promote expression of a short half‐life green fluorescent protein following glucocorticoid receptor activation. Herein, we document the ability of this reporter line to respond to both chronic and acute exogenous glucocorticoid treatment. The green fluorescent protein expression in response to transgene activation was high in a variety of tissues including the brain, and provided single‐cell resolution in the effected regions. The specificity of these responses is demonstrated using the partial agonist mifepristone and mutation of the glucocorticoid receptor. Importantly, the reporter line also modeled the temporal dynamics of endogenous stress response signaling, including the increased production of the glucocorticoid cortisol following hyperosmotic stress and the fluctuations of basal cortisol concentrations with the circadian rhythm. Taken together, these results characterize our newly developed reporter line for elucidating environmental or genetic modifiers of stress response signaling, which may provide insights to the neuronal mechanisms underlying neuropsychiatric disorders such as major depressive disorder.

Context.— BCL6 translocations are a frequent finding in B-cell lymphomas of diverse subtypes, including some cases of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). However, reliable analysis of BCL6 rearrangements using fluorescence in situ hybridization is difficult in NLPHL because of the relative paucity of neoplastic cells. Combined immunofluorescence microscopy and fluorescence in situ hybridization, or fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms (FICTION), permits targeted analysis of neoplastic cells. Objective.— To better define the spectrum of BCL6 abnormalities in NLPHL using FICTION analysis. Design.— We performed an optimized FICTION analysis of 24 lymph nodes, including 11 NLPHL, 5 follicular hyperplasia with prominent progressive transformation of germinal centers, and 8 follicular hyperplasia without progressive transformation of germinal centers. Results.— BCL6 rearrangement was identified in 5 of 11 cases of NLPHL (46%). In addition, BCL6 gene amplification, with large clusters of BCL6 signals in the absence of chromosome 3 aneuploidy, was detected in 3 of 11 cases of NLPHL (27%). One NLPHL showed extra copies of BCL6 present in conjunction with multiple copies of chromosome 3. Altogether, we detected BCL6 abnormalities in 9 of 11 cases of NLPHL (82%). None of the progressive transformation of germinal centers or follicular hyperplasia cases showed BCL6 abnormalities by FICTION. Conclusions.— To our knowledge, this is the first report of BCL6 gene amplification in NLPHL. Our optimized protocol for FICTION permits detection of cytogenetic abnormalities in most NLPHL cases and may represent a useful ancillary diagnostic technique.