Should I Take Aspirin? (SITA): RCT of a decision aid for cancer chemoprevention.

Background Australian guidelines recommend that all people aged 50-70 years old consider taking low-dose aspirin to reduce the risk of colorectal cancer (CRC). Aim To determine the effect of a consultation with a researcher in general practice using a decision aid about taking low-dose aspirin to prevent CRC on informed decision-making and low-dose aspirin uptake compared to a general CRC prevention brochure. Design and Setting Individually randomised controlled trial in six general practices in Victoria, Australia, from October 2020 to March 2021. Method Patients aged 50-70 years attending a general practitioner (GP) were recruited consecutively. The intervention was a consultation using a decision aid to discuss taking aspirin to reduce CRC risk; control consultations discussed reducing CRC risk generally. The self-reported co-primary outcomes were informed choices about taking aspirin at one month and low-dose aspirin uptake at six months. Results 261 participants (86% of eligible patients) were randomised into trial arms (129 intervention, 132 control). 17.7% (20/113) of intervention and 7.6% (9/118) control participants reported making an informed choice at one month, an estimated 9.1% (95% CI 0.29% to 18.5) between-arm difference in proportions [odds ratio (OR) 2.47 (97.5% CI:0.94 to 6.52) p=0.074]. The proportions of individuals who reported using aspirin at six months were: 10.2% (12/118) intervention vs 13.8% (16/116) control (estimated between-arm difference: -4.0% (95% CI: -13.5 to 5.5); [OR= 0.68 (97.5% CI:0.27 to 1.70), p= 0.692]. Conclusion The decision aid improved informed decision-making; but has little effect on long-term regular use of aspirin to reduce CRC risk

Sequence-Specific Binding of Recombinant Zbed4 to DNA: Insights into Zbed4 Participation in Gene Transcription and Its Association with Other Proteins

Zbed4, a member of the BED subclass of Zinc-finger proteins, is expressed in cone photoreceptors and glial Müller cells of human retina whereas it is only present in Müller cells of mouse retina. To characterize structural and functional properties of Zbed4, enough amounts of purified protein were needed. Thus, recombinant Zbed4 was expressed in E. coli and its refolding conditions optimized for the production of homogenous and functionally active protein. Zbed4’s secondary structure, determined by circular dichroism spectroscopy, showed that this protein contains 32% α-helices, 18% β-sheets, 20% turns and 30% unordered structures. CASTing was used to identify the target sites of Zbed4 in DNA. The majority of the DNA fragments obtained contained poly-Gs and some of them had, in addition, the core signature of GC boxes; a few clones had only GC-boxes. With electrophoretic mobility shift assays we demonstrated that Zbed4 binds both not only to DNA and but also to RNA oligonucleotides with very high affinity, interacting with poly-G tracts that have a minimum of 5 Gs; its binding to and GC-box consensus sequences. However, the latter binding depends on the GC-box flanking nucleotides. We also found that Zbed4 interacts in Y79 retinoblastoma cells with nuclear and cytoplasmic proteins Scaffold Attachment Factor B1 (SAFB1), estrogen receptor alpha (ERα), and cellular myosin 9 (MYH9), as shown with immunoprecipitation and mass spectrometry studies as well as gel overlay assays. In addition, immunostaining corroborated the co-localization of Zbed4 with these proteins. Most importantly, in vitro experiments using constructs containing promoters of genes directing expression of the luciferase gene, showed that Zbed4 transactivates the transcription of those promoters with poly-G tracts

A DNA Vaccine Encoding Multiple HIV CD4 Epitopes Elicits Vigorous Polyfunctional, Long-Lived CD4+ and CD8+ T Cell Responses

T-cell based vaccines against HIV have the goal of limiting both transmission and disease progression by inducing broad and functionally relevant T cell responses. Moreover, polyfunctional and long-lived specific memory T cells have been associated to vaccine-induced protection. CD4+ T cells are important for the generation and maintenance of functional CD8+ cytotoxic T cells. We have recently developed a DNA vaccine encoding 18 conserved multiple HLA-DR-binding HIV-1 CD4 epitopes (HIVBr18), capable of eliciting broad CD4+ T cell responses in multiple HLA class II transgenic mice. Here, we evaluated the breadth and functional profile of HIVBr18-induced immune responses in BALB/c mice. Immunized mice displayed high-magnitude, broad CD4+/CD8+ T cell responses, and 8/18 vaccine-encoded peptides were recognized. In addition, HIVBr18 immunization was able to induce polyfunctional CD4+ and CD8+ T cells that proliferate and produce any two cytokines (IFNγ/TNFα, IFNγ/IL-2 or TNFα/IL-2) simultaneously in response to HIV-1 peptides. For CD4+ T cells exclusively, we also detected cells that proliferate and produce all three tested cytokines simultaneously (IFNγ/TNFα/IL-2). The vaccine also generated long-lived central and effector memory CD4+ T cells, a desirable feature for T-cell based vaccines. By virtue of inducing broad, polyfunctional and long-lived T cell responses against conserved CD4+ T cell epitopes, combined administration of this vaccine concept may provide sustained help for CD8+ T cells and antibody responses- elicited by other HIV immunogens

Dimensional and hierarchical models of depression using the Beck Depression Inventory-II in an Arab college student sample

Abstract Background An understanding of depressive symptomatology from the perspective of confirmatory factor analysis (CFA) could facilitate valid and interpretable comparisons across cultures. The objectives of the study were: (i) using the responses of a sample of Arab college students to the Beck Depression Inventory (BDI-II) in CFA, to compare the "goodness of fit" indices of the original dimensional three-and two-factor first-order models, and their modifications, with the corresponding hierarchical models (i.e., higher - order and bifactor models); (ii) to assess the psychometric characteristics of the BDI-II, including convergent/discriminant validity with the Hopkins Symptom Checklist (HSCL-25). Method Participants (N = 624) were Kuwaiti national college students, who completed the questionnaires in class. CFA was done by AMOS, version 16. Eleven models were compared using eight "fit" indices. Results In CFA, all the models met most "fit" criteria. While the higher-order model did not provide improved fit over the dimensional first - order factor models, the bifactor model (BFM) had the best fit indices (CMNI/DF = 1.73; GFI = 0.96; RMSEA = 0.034). All regression weights of the dimensional models were significantly different from zero (P Conclusion The broadly adequate fit of the various models indicates that they have some merit and implies that the relationship between the domains of depression probably contains hierarchical and dimensional elements. The bifactor model is emerging as the best way to account for the clinical heterogeneity of depression. The psychometric characteristics of the BDI-II lend support to our CFA results.</p

Feasibility studies for the measurement of time-like proton electromagnetic form factors from p¯ p→ μ+μ- at P ¯ ANDA at FAIR

This paper reports on Monte Carlo simulation results for future measurements of the moduli of time-like proton electromagnetic form factors, | GE| and | GM| , using the p¯ p→ μ+μ- reaction at P ¯ ANDA (FAIR). The electromagnetic form factors are fundamental quantities parameterizing the electric and magnetic structure of hadrons. This work estimates the statistical and total accuracy with which the form factors can be measured at P ¯ ANDA , using an analysis of simulated data within the PandaRoot software framework. The most crucial background channel is p¯ p→ π+π-, due to the very similar behavior of muons and pions in the detector. The suppression factors are evaluated for this and all other relevant background channels at different values of antiproton beam momentum. The signal/background separation is based on a multivariate analysis, using the Boosted Decision Trees method. An expected background subtraction is included in this study, based on realistic angular distributions of the background contribution. Systematic uncertainties are considered and the relative total uncertainties of the form factor measurements are presented