Chromatin accessibility-based characterisation of brain gene regulatory networks in three distinct honey bee polyphenisms.

The honey bee genome has the capacity to produce three phenotypically distinct organisms (two diploid female castes: queen and worker, and a haploid male drone). Previous studies have implicated metabolic flux acting via epigenetic regulation in directing nutrition-driven phenotypic plasticity in the honey bee. However, the cis-acting DNA regulatory elements that establish tissue and polyphenism -specific epigenomes and gene expression programmes, remain unclear. Using a high resolution multiomic approach including assay for transposase-accessible chromatin by sequencing (ATAC-seq), RNA-seq and ChIP-seq, we produce the first genome-wide maps of the regulatory landscape across all three adult honey bee phenotypes identifying > 5000 regulatory regions in queen, 7500 in worker and 6500 in drone, with the vast majority of these sites located within intronic regions. These regions are defined by positive enrichment of H3K27ac and depletion of H3K4me3 and show a positive correlation with gene expression. Using ATAC-seq footprinting we determine queen, worker and drone -specific transcription factor occupancy and uncover novel phenotype-specific regulatory networks identifying two key nuclear receptors that have previously been implicated in caste-determination and adult behavioural maturation in honey bees; ecdysone receptor and ultraspiracle. Collectively, this study provides novel insights into key gene regulatory networks that are associated with these distinct polyphenisms in the honey bee.

The PWWP domain and the evolution of unique DNA methylation toolkits in Hymenoptera.

DNMT3 in Hymenoptera has a unique duplication of the essential PWWP domain. Using GST-tagged PWWP fusion proteins and histone arrays we show that these domains have gained new properties and represent the first case of PWWP domains binding to H3K27 chromatin modifications, including H3K27me3, a key modification that is important during development. Phylogenetic analyses of 107 genomes indicate that the duplicated PWWP domains separated into two sister clades, and their distinct binding capacities are supported by 3D modeling. Other features of this unique DNA methylation system include variable copies, losses, and duplications of DNMT1 and DNMT3, and combinatorial generations of DNMT3 isoforms including variants missing the catalytic domain. Some of these losses and duplications of are found only in parasitic wasps. We discuss our findings in the context of the crosstalk between DNA methylation and histone methylation, and the expanded potential of epigenomic modifications in Hymenoptera to drive evolutionary novelties.

Coronary-artery revascularization before elective major vascular surgery.

BACKGROUND: The benefit of coronary-artery revascularization before elective major vascular surgery is unclear. METHODS: We randomly assigned patients at increased risk for perioperative cardiac complications and clinically significant coronary artery disease to undergo either revascularization or no revascularization before elective major vascular surgery. The primary end point was long-term mortality. RESULTS: Of 5859 patients scheduled for vascular operations at 18 Veterans Affairs medical centers, 510 (9 percent) were eligible for the study and were randomly assigned to either coronary-artery revascularization before surgery or no revascularization before surgery. The indications for a vascular operation were an expanding abdominal aortic aneurysm (33 percent) or arterial occlusive disease of the legs (67 percent). Among the patients assigned to preoperative coronary-artery revascularization, percutaneous coronary intervention was performed in 59 percent, and bypass surgery was performed in 41 percent. The median time from randomization to vascular surgery was 54 days in the revascularization group and 18 days in the group not undergoing revascularization (P<0.001). At 2.7 years after randomization, mortality in the revascularization group was 22 percent and in the no-revascularization group 23 percent (relative risk, 0.98; 95 percent confidence interval, 0.70 to 1.37; P=0.92). Within 30 days after the vascular operation, a postoperative myocardial infarction, defined by elevated troponin levels, occurred in 12 percent of the revascularization group and 14 percent of the no-revascularization group (P=0.37). CONCLUSIONS: Coronary-artery revascularization before elective vascular surgery does not significantly alter the long-term outcome. On the basis of these data, a strategy of coronary-artery revascularization before elective vascular surgery among patients with stable cardiac symptoms cannot be recommended.

Long-term patency of saphenous vein and left internal mammary artery grafts after coronary artery bypass surgery: results from a Department of Veterans Affairs Cooperative Study.

OBJECTIVES: This study defined long-term patency of saphenous vein grafts (SVG) and internal mammary artery (IMA) grafts. BACKGROUND: This VA Cooperative Studies Trial defined 10-year SVG patency in 1,074 patients and left IMA patency in 457 patients undergoing coronary artery bypass grafting (CABG). METHODS: Patients underwent cardiac catheterizations at 1 week and 1, 3, 6, and 10 years after CABG. RESULTS: Patency at 10 years was 61% for SVGs compared with 85% for IMA grafts (p < 0.001). If a SVG or IMA graft was patent at 1 week, that graft had a 68% and 88% chance, respectively, of being patent at 10 years. The SVG patency to the left anterior descending artery (LAD) (69%) was better (p < 0.001) than to the right coronary artery (56%), or circumflex (58%). Recipient vessel size was a significant predictor of graft patency, in vessels >2.0 mm in diameter SVG patency was 88% versus 55% in vessels 2.0 mm in diameter.

Acculturation, health protective sexual communication, and HIV/AIDS risk behavior among Hispanic women in a large midwestern city.

The relationships among acculturation, health protective sexual communication, and HIV/AIDS risk behaviors of Hispanic women are examined. Respondents represented 14 Latin American countries, a mean age of 29.5 years, and relatively low education and income levels. A significant correlation was found between higher non-Hispanic acculturation level and higher sexual communication with new partners. Higher non-Hispanic acculturation levels were also correlated with higher number of sexual partners in the prior 12 months. The higher the score for health protective sexual communication, the higher the reported frequency of condom use with new sexual partners in the past 12 months. Given the low number of sexual partners, HIV/AIDS risk for this group of women appears to be related to not knowing whether their partners had other sexual partners and to low frequency of condom use. Implications for health education are discussed.

A cross-validation of safety climate scale using confirmatory factor analytic approach.

PROBLEM: Given the lack of a consistent factor structure of safety climate, this study tested the stability of a factor structure of a safety climate scale developed through an extensive literature review using confirmatory factor analytic approach and cross-validation. METHODS: A cross-sectional sample of 722 U.S. grain industry workers participated in the questionnaire survey. RESULTS: The safety climate scale developed through the generation of an item pool based on a table of specifications, subsequent scientific item reduction procedures, reviews from experts, and pilot test yielded adequate reliabilities for each dimension. Each item showed proper discriminative power based on both internal and external criteria. Criterion validity was manifested by the significant positive correlation of the scale with five criteria. Evidence of construct validity was provided by both exploratory and confirmatory factor analyses. Both calibration and validation samples supported a consistent factor structure. Management commitment and supervisor support were found to influence other dimensions of safety climate. DISCUSSION: This study provides an insight into the primary reason why previous attempts have failed to find a consistent factor structure of safety climate: No specification of the influence of management commitment and supervisor support on other dimensions of safety in their models. IMPACT ON INDUSTRY: The findings of this study provide a framework upon which accident prevention efforts can be effectively organized and underscore the importance of management commitment and supervisor support as they affect employee safety perceptions.

The use of zoledronic acid in men receiving androgen deprivation therapy for prostate cancer with severe osteopenia or osteoporosis.

OBJECTIVES: To study the effect of zoledronic acid on patients with pre-existing osteoporosis on androgen deprivation therapy (ADT), who are at highest risk for fracture. Zoledronic acid is a potent bisphosphonate that can prevent osteoporosis in patients with nonmetastatic (M0), prostate cancer (CaP) who are initiating ADT. The effect of zoledronic acid on patients with pre-existing osteoporosis on ADT, who are highest risk for fracture, has not been adequately studied. METHODS: We enrolled 28 patients with M0 CaP on ADT with severe osteopenia or osteoporosis (baseline bone-mineral density (BMD) T score < -2.0) in this open-label, single-arm trial to assess the effect of zoledronic acid on BMD. All patients also received supplemental calcium and vitamin D, and were counseled about lifestyle modifications. Patients received zoledronic acid (4 mg) intravenously every 3 months for 4 treatments. BMD was measured by dual energy X-ray absorptiometry scan at enrollment, 6 and 12 months. Primary endpoint was percent change in lumbar spine BMD. RESULTS: This was a high-risk patient population-primarily older Caucasians (mean age, 73 years), former smokers, and moderate users of alcohol. Mean duration of ADT was 2.4 years. Pre-existing osteopenia or osteoporosis was observed in a single site in 9 patients and multiple sites in 19 (68%). After 12 months of zoledronic acid, lumbar spine BMD increased 4.17% (P < .0001), and BMD increased significantly (P < .05) in both hips and the right femoral neck. Seven patients (25%) experienced improved BMD into the nonosteoporotic range (T score > -2.0). Zoledronic acid infusion was well tolerated and without substantial renal toxicity. CONCLUSIONS: Zoledronic acid improves BMD in men with M0 CaP on ADT with severe osteopenia or osteoporosis (T scores < 2.0). This novel finding identifies a high-risk patient population that can potentially benefit from bisphosphonate therapy.

Economic evaluation of blind rehabilitation for veterans with macular diseases in the Department of Veterans Affairs.

PURPOSE: The Department of Veterans Affairs (VA) Low Vision Intervention Trial (LOVIT) developed an outpatient low-vision programme for patients with macular diseases providing low-vision rehabilitation comparable to VA inpatient blind rehabilitation centres (BRCs). This programme targets veterans who do not need or chose not to participate in a comprehensive inpatient blind rehabilitation programme. We examined costs and consequences using veterans in LOVIT and comparable veterans in an inpatient BRC. METHODS: We compared costs and consequences between treatment patients who participated in LOVIT, a two-site randomized clinical trial, and a sample of comparable patients who received treatment at a VA inpatient BRC. We measured consequences as the change in functional visual ability from baseline to follow-up (LOVIT: 4 months after randomization; BRC: 3 months after discharge) using the VA Low Vision Visual Functioning Questionnaire (VA LV VFQ-48). RESULTS: There were 55 LOVIT and 121 BRC patients for our analyses. Average costs were $38,627.3 higher for BRC patients ($5,054.4 +/- $404.7 SD for LOVIT vs. $43,681.7 +/- $8,853.6 SD for BRC, p < 0.0001). Thus, the BRC cost $38,627.3 per patient more than the LOVIT programme (95% CI: $17,414 to $273,482). There was a greater improvement in overall visual ability, mobility, and visual motor skill scores for BRC patients; however, there was no significant difference in improvement in reading ability or visual information processing scores. CONCLUSIONS: As VA increases outpatient blind rehabilitation services, LOVIT provides a model for expanding outpatient low-vision rehabilitation services for veterans at substantially lower costs than current inpatient BRC services.

The Veterans Affairs Low Vision Intervention Trial (LOVIT): design and methodology.

BACKGROUND: Visual impairment is a major public health problem. Vision rehabilitation programs have the potential to restore independence and improve quality of life for persons with permanent vision loss, and few have been evaluated in randomized controlled trials. PURPOSE: The Veterans Affairs (VA) Low Vision Intervention Trial is a multicenter randomized clinical trial to evaluate the effectiveness of a new outpatient low vision rehabilitation program. METHODS: 126 patients with moderate and severe vision loss due to macular diseases are randomized to low vision treatment in an outpatient setting or a usual care control group at two VA facilities in Hines, Illinois, and Salisbury, North Carolina. The primary outcome is the change in visual reading ability from baseline to four months measured with the Veterans Affairs Low Vision Visual Functioning Questionnaire-48 (VA LV VFQ-48). Secondary outcomes compare the mean change in visual ability measured with the VA LV VFQ-48 (overall ability, mobility, visual information processing, visual motor skills) for the treatment and control groups. Costs and cost effectiveness of outpatient treatment are evaluated. RESULTS: The low vision rehabilitation setting, use of a waiting list control group to address ethical issues, development of the treatment protocol, development of a vision function questionnaire for patients to self-report the difficulty they experience performing daily activities, and the use of Rasch analysis to develop and estimate this outcome measure are described. LIMITATIONS: If the new low vision rehabilitation program is proven effective, studies will be needed to determine which of the multiple aspects of the intervention are necessary and sufficient. CONCLUSIONS: The challenges of conducting clinical trials in a rehabilitation setting and use of a waiting list (deferred treatment) control group extend beyond LOVIT. The design and methods of LOVIT may be applicable to other trials of rehabilitation services and to outcomes for which reliable and valid measurement tools must be developed.