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This study strengthens the evidence for a significant effect of HIV infection on the natural history of chronic HBV infection, which by prolonging the period of infectivity could have an important impact on the epidemiology of HBV infection in regions, or patient groups, with high HIV seroprevalence. There was no evidence of an important effect of HBV carriage on HIV disease progression.

Purpose : Associations between p160 coactivator proteins and the development of resistance to endocrine treatment have been described. We hypothesized that nuclear receptor coregulatory proteins may interact with nonsteroid receptors. We investigated the mitogen-activated protein kinase -activated transcription factors, Ets, as possible interaction proteins for the coactivators SRC-1 and AIB1 and the corepressor NCoR in human breast cancer.Experimental Design: Expression and coexpression of Ets and the coregulatory proteins was investigated using immunohistochemistry and immunofluorescence in a cohort of breast tumor patients (N = 134). Protein expression, protein-DNA interactions and protein-protein interactions were assessed using Western blot, electromobility shift, and coimmunoprecipitation analysis, respectively.Results: Ets-1 and Ets-2 associated with reduced disease-free survival (P < 0.0292, P < 0.0001, respectively), whereas NCoR was a positive prognostic indicator (P < 0.0297). Up-regulation of Ets-1 protein expression in cell cultures derived from patient tumors in the presence of growth factors associated with tumor grade (P < 0.0013; n = 28). In primary breast tumor cell cultures and in the SKBR3 breast cell line, growth factors induced interaction between Ets and their DNA response element, induced recruitment of coactivators to the transcription factor-DNA complex, and up-regulated protein expression of HER2. Ets-1 and Ets-2 interacted with the coregulators under basal conditions, and growth factors up-regulated Ets-2 interaction with SRC-1 and AIB1. Coexpression of Ets-2 and SRC-1 significantly associated with the rate of recurrence and HER expression, compared with patients who expressed Ets-2 but not SRC-1 (P < 0.0001 and P < 0.0001, respectively).Conclusions: These data describe associations and interactions between nonsteroid transcription factors and coregulatory proteins in human breast cancer.

Background: In human breast cancer, the growth factor receptor HER2 is associated with disease progression and resistance to endocrine treatment. Growth factor induced mitogen activated protein kinase activity can phosphorylate not only the oestrogen receptor, but also its coactivator proteins AIB1 and SRC-1. Aim: To determine whether insensitivity to endocrine treatment in HER2 positive patients is associated with enhanced expression of coactivator proteins, expression of the HER2 transcriptional regulator, PEA3, and coregulatory proteins, AIB1 and SRC-1, was assessed in a cohort of patients with breast cancer of known HER2 status. Methods: PEA3, AIB1, and SRC-1 protein expression in 70 primary breast tumours of known HER2 status (HER2 positive, n = 35) and six reduction mammoplasties was assessed using immunohistochemistry. Colocalisation of PEA3 with AIB1 and SRC-1 was determined using immunofluorescence. Expression of PEA3, AIB1, and SRC-1 was correlated with clinicopathological parameters. Results: In primary breast tumours expression of PEA3, AIB1, and SRC-1 was associated with HER2 status (p = 0.0486, p = 0.0444, and p = 0.0012, respectively). In the HER2 positive population, PEA3 expression was associated with SRC-1 (p = 0.0354), and both PEA3 and SRC-1 were significantly associated with recurrence on univariate analysis (p = 0.0345; p,0.0001). On multivariate analysis, SRC-1 was significantly associated with disease recurrence in HER2 positive patients (p = 0.0066). Conclusion: Patients with high expression of HER2 in combination with SRC-1 have a greater probability of recurrence on endocrine treatment compared with those who are HER2 positive but SRC-1 negative. SRC-1 may be an important predictive indicator and therapeutic target in breast cancer.

BackgroundObesity and its measure of body mass index are strongly determined by parental body size. Debate continues as to whether both parents contribute equally to offspring body mass which is key to understanding the aetiology of the disease. The aim of this study was to use cohort data from three generations of one family to examine the relative maternal and paternal associations with offspring body mass index and how these associations compare with family height to demonstrate evidence of genetic or environmental cross-generational transmission.Methods669 of 1082 families were followed up in 2007/8 as part of the Lifeways study, a prospective observational cross-generation linkage cohort. Height and weight were measured in 529 Irish children aged 5 to 7 years and were self-reported by parents and grandparents. All adults provided information on self-rated health, education status, and indicators of income, diet and physical activity. Associations between the weight, height, and body mass index of family members were examined with mixed models and heritability estimates computed using linear regression analysis.ResultsSelf-rated health was associated with lower BMI for all family members, as was age for children. When these effects were accounted for evidence of familial associations of BMI from one generation to the next was more apparent in the maternal line. Heritability estimates were higher (h2 = 0.40) for mother-offspring pairs compared to father-offspring pairs (h2 = 0.22). In the previous generation, estimates were higher between mothers-parents (h2 = 0.54-0.60) but not between fathers-parents (h2 = -0.04-0.17). Correlations between mother and offspring across two generations remained significant when modelled with fixed variables of socioeconomic status, health, and lifestyle. A similar analysis of height showed strong familial associations from maternal and paternal lines across each generation.ConclusionsThis is the first family cohort study to report an enduring association between mother and offspring BMI over three generations. The evidence of BMI transmission over three generations through the maternal line in an observational study corroborates the findings of animal studies. A more detailed analysis of geno and phenotypic data over three generations is warranted to understand the nature of this maternal-offspring relationship.

The oestrogen receptor (ER) interacts with coactivator proteins to modulate genes central to breast tumour progression. Oestrogen receptor is encoded for by two genes, ER-a and ER-b. Although ER-a has been well characterized, the role of ER-b as a prognostic indicator remains unresolved. To determine isoform-specific expression of ER and coexpression with activator proteins, we examined the expression and localisation of ER-a, ER-b and the coactivator protein steroid receptor coactivator 1 (SRC-1) by immunohistochemistry and immunofluorescence in a cohort of human breast cancer patients (n ¼ 150). Relative levels of SRC-1 in primary breast cultures derived from patient tumours in the presence of b-oestradiol and tamoxifen was assessed using Western blotting (n ¼ 14). Oestrogen receptor-b protein expression was associated with disease-free survival (DFS) and inversely associated with the expression of HER2 (P ¼ 0.0008 and Po0.0001, respectively), whereas SRC-1 was negatively associated with DFS and positively correlated with HER2 (Po0.0001 and Po0.0001, respectively). Steroid receptor coactivator 1 protein expression was regulated in response to b-oestradiol or tamoxifen in 57% of the primary tumour cell cultures. Protein expression of ER-b and SRC-1 was inversely associated (P ¼ 0.0001). The association of ER-b protein expression with increased DFS and its inverse relationship with SRC-1 suggests a role for these proteins in predicting outcome in breast cancer.

There is a perception that university students have changed dramatically in their modes of learning in recent years, mainly due to their widespread use of the Internet as an information source, the change in student body due to the greater accessibility of third level education and changes in experience in second level education. Lectures, however, remain the central mode of traditional teaching and learning at most universities and thus attendance at lectures continues to be a subject of considerable importance. However, few studies report actual attendance levels in any comprehensive way. Herein, levels of lecture attendance in the colleges of Science in University College Dublin are documented from two probability-based surveys. The results of a questionnaire recording the attitudes of students towards a range of factors that potentially affect attendance are also presented. Factors that continue to influence attendance, that are in the control of the university, such as living on/off campus, the lecture schedule in the students' timetable, day of the week and transport problems are revealed. Factors in students' personal lives, such as engagement in part-time work, irrespective of purpose, are seen to be related to satisfaction with studies and lecture delivery. Suggestions for active measures to increase the level of lecture attendance, appropriate to the present day, are made.

Objective-To determine the prevalence of hepatitis C virus infection and associated risk factors in patients attending a genitourinary medicine clinic, as evidence for sexual transmission.Design-Seroprevalence estimated by reactivity in an enzyme immunoassay for antibodies to C100 protein with supplementary testing with a recombinant immunoblot assay and an assay for hepatitis C virus RNA.Setting-Outpatient genitourinary medicine clinic in central London.Patients