Measuring patient perceptions about osteoporosis pharmacotherapy

Abstract Background Adherence to osteoporosis pharmacotherapy is poor, and linked with patient perceptions of the benefits of, and barriers to taking these treatments. To better understand the association between patient perceptions and osteoporosis pharmacotherapy, we generated thirteen items that may tap into patient perceptions about the benefits of, and barriers to osteoporosis treatment; and included these items as part of a standardized telephone interview of women aged 65–90 years (n = 871). The purpose of this paper is to report the psychometric evaluation of our scale. Findings Upon detailed analysis, six of the thirteen items were omitted: four redundant, one did not correlate well with any other item and one factorial complex. From the remaining seven items, two distinct unidimensional domains emerged (variance explained = 78%). Internal consistency of the 5-item osteoporosis drug treatment benefits domain was good (Cronbach's alpha = 0.88), and was supported by construct validity; women reporting a physician-diagnosis or taking osteoporosis pharmacotherapy had higher osteoporosis treatment benefit scores compared to those reporting no osteoporosis diagnosis or treatment respectively. Because only two items were identified as tapping into treatment barriers, we recommend they each be used as a separate item assessing potential barriers to adherence to osteoporosis pharmacotherapy, rather than combined into a single scale. Conclusion The 5-item osteoporosis drug treatment benefits scale may be useful to examine perceptions about the benefits of osteoporosis pharmacotherapy. Further research is needed to develop scales that adequately measure perceived barriers to osteoporosis pharmacotherapy

Facial image manipulation : A tool for investigating social perception

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by the Australian Research Council (ARC) Centre of Excellence in Cognition and its Disorders (CE110001021), an ARC Discovery Outstanding Researcher Award to Rhodes (DP130102300), and an ARC Discovery grant to Rhodes, Sutherland, and Young (DP170104602).Peer reviewedPostprin

Sexual unfaithfulness can be judged with some accuracy from men's but not women's faces

Peer reviewedPublisher PD

Predictors of locating women six to eight years after contact: internet resources at recruitment may help to improve response rates in longitudinal research

<p>Abstract</p> <p>Background</p> <p>The ability to locate those sampled has important implications for response rates and thus the success of survey research. The purpose of this study was to examine predictors of locating women requiring tracing using publicly available methods (primarily Internet searches), and to determine the additional benefit of vital statistics linkages.</p> <p>Methods</p> <p>Random samples of women aged 65–89 years residing in two regions of Ontario, Canada were selected from a list of those who completed a questionnaire between 1995 and 1997 (n = 1,500). A random sample of 507 of these women had been searched on the Internet as part of a feasibility pilot in 2001. All 1,500 women sampled were mailed a newsletter and information letter prior to recruitment by telephone in 2003 and 2004. Those with returned mail or incorrect telephone number(s) required tracing. Predictors of locating women were examined using logistic regression.</p> <p>Results</p> <p>Tracing was required for 372 (25%) of the women sampled, and of these, 181 (49%) were located. Predictors of locating women were: younger age, residing in less densely populated areas, having had a web-search completed in 2001, and listed name identified on the Internet prior to recruitment in 2003. Although vital statistics linkages to death records subsequently identified 41 subjects, these data were incomplete.</p> <p>Conclusion</p> <p>Prospective studies may benefit from using Internet resources at recruitment to determine the listed names for telephone numbers thereby facilitating follow-up tracing and improving response rates. Although vital statistics linkages may help to identify deceased individuals, these may be best suited for post hoc response rate adjustment.</p

DNA replication stress restricts ribosomal DNA copy number

Ribosomal RNAs (rRNAs) in budding yeast are encoded by ~100–200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA) locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how “normal” copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen a yeast conditional temperature-sensitive mutant collection of essential genes. Our screen revealed that low rDNA copy number is associated with compromised DNA replication. Further, subculturing yeast under two separate conditions of DNA replication stress selected for a contraction of the rDNA array independent of the replication fork blocking protein, Fob1. Interestingly, cells with a contracted array grew better than their counterparts with normal copy number under conditions of DNA replication stress. Our data indicate that DNA replication stresses select for a smaller rDNA array. We speculate that this liberates scarce replication factors for use by the rest of the genome, which in turn helps cells complete DNA replication and continue to propagate. Interestingly, tumors from mini chromosome maintenance 2 (MCM2)-deficient mice also show a loss of rDNA repeats. Our data suggest that a reduction in rDNA copy number may indicate a history of DNA replication stress, and that rDNA array size could serve as a diagnostic marker for replication stress. Taken together, these data begin to suggest the selective pressures that combine to yield a “normal” rDNA copy number

Development of a psychological intervention for fatigue after stroke

Post-stroke fatigue (PSF) is common and distressing, but there is insufficient evidence to recommend any effective treatment for it. Psychological interventions are effective in treating fatigue in other conditions. This paper describes the development and evaluation of the feasibility of a psychological intervention for PSF.Based on psychological correlates of PSF and evidence-based psychological interventions for fatigue in other medical conditions, we developed a manualised psychological intervention for PSF, with input from stroke clinicians, psychological therapists, and stroke survivors. The intervention was delivered by a clinical psychologist to 12 participants with PSF to test its acceptability and feasibility. According to the feedback from participants and therapists, the intervention was refined for future use.The intervention consisted of six individual, face-to-face treatment sessions, and one follow-up, telephone-delivered booster session. It included psycho-education and discussion of strategies to promote physical and social activities and to challenge unhelpful thoughts. Four participants dropped out and the remaining eight participants completed the intervention. These eight participants also completed all assessments and feedback and reported fatigue levels as lower at the end of the study than at the baseline. All participants reported favourable opinions on the intervention and suggested that the last two treatment sessions be combined and the booster session be delivered in person as opposed to telephone.This psychological intervention was acceptable to stroke patients and was feasible in the local health service. These findings suggest that a randomised controlled trial to test efficacy is warranted

Comparing the frequency of common genetic variants and haplotypes between carriers and non-carriers of BRCA1 and BRCA2 deleterious mutations in Australian women diagnosed with breast cancer before 40 years of age

BACKGROUND: BRCA1 and BRCA2 mutations are found in a proportion of families with multiple early-onset breast cancers. There are a large number of different deleterious mutations in both genes, none of which would be detectable using standard genetic association studies. Single common variants and haplotypes of common variants may capture groups of deleterious mutations since some low prevalence haplotypes of common variants occur more frequently among chromosomes that carry rare, deleterious mutations than chromosomes that do not. METHODS: DNA sequence data for BRCA1 and BRCA2 was obtained from 571 participants from the Australian Breast Cancer Family Study. Genetic variants were classified as either deleterious mutations or common genetic variants. Variants tagging common polymorphisms were selected and haplotypes resolved using Haploview. Their frequency was compared to those with and without deleterious mutations using a permutation test. RESULTS: A common genetic variant in BRCA1 (3232A > G) was found to be over-represented in deleterious mutation carriers (p = 0.05), whereas a common genetic variant in BRCA2 (1342A > C) occurred less frequently in deleterious mutation carriers (p = 0.04). All four of the common BRCA1 variants used to form haplotypes occurred more frequently in the deleterious mutation carriers when compared to the non-carriers, but there was no evidence of a difference in the distributions between the two groups (p = 0.34). In BRCA2, all four common variants were found to occur less frequently in the deleterious mutation carriers when compared to non-carriers, but the evidence for difference in the distribution between the two groups was weak (p = 0.16). Several less common haplotypes of common BRCA1 variants were found to be over-represented among deleterious mutation carriers but there was no evidence for this at the population level. In BRCA2, only the most common haplotype was found to occur more frequently in deleterious mutation carriers, with again no evidence at the population level. CONCLUSIONS: We observed differences in the frequency of common genetic variants of the BRCA1 and BRCA2 and their haplotypes between early-onset breast cancer cases who did and did not carry deleterious mutations in these genes. Although our data provide only weak evidence for a difference in frequencies at the population level, the number of deleterious mutation carriers was low and the results may yet be substantiated in a larger study using pooled data

Medroxyprogesterone Acetate Alters Mycobacterium Bovis BCG-Induced Cytokine Production in Peripheral Blood Mononuclear Cells of Contraceptive Users

Most individuals latently infected with Mycobacterium tuberculosis (M.tb) contain the infection by a balance of effector and regulatory immune responses. This balance can be influenced by steroid hormones such as glucocorticoids. The widely used contraceptive medroxyprogesterone acetate (MPA) possesses glucocorticoid activity. We investigated the effect of this hormone on immune responses to BCG in household contacts of active TB patients. Multiplex bead array analysis revealed that MPA demonstrated both glucocorticoid and progestogenic properties at saturating and pharmacological concentrations in peripheral blood mononuclear cells (PBMCs) and suppressed antigen specific cytokine production. Furthermore we showed that PBMCs from women using MPA produced significantly lower levels of IL-1α, IL-12p40, IL-10, IL-13 and G-CSF in response to BCG which corresponded with lower numbers of circulating monocytes observed in these women. Our research study is the first to show that MPA impacts on infections outside the genital tract due to a systemic effect on immune function. Therefore MPA use could alter susceptibility to TB, TB disease severity as well as change the efficacy of new BCG-based vaccines, especially prime-boost vaccine strategies which may be administered to adult or adolescent women in the future

ADAM15 mediates upregulation of Claudin-1 expression in breast cancer cells

A Disintegrin and Metalloproteinase-15 (ADAM15) is a transmembrane protein involved in protein ectodomain shedding, cell adhesion and signalling. We previously cloned and characterised alternatively spliced variants of ADAM15 that differ in their intracellular domains and demonstrated correlation of the expression of specific variants with breast cancer prognosis. In this study we have created isogenic cell panels (MDA-MB-231 and MCF-7) expressing five ADAM15 variants including wildtype and catalytically inactive forms. The expression of ADAM15 isoforms in MDA-MB-231 cells led to cell clustering to varying degree, without changes in EMT markers vimentin, slug and E-cadherin. Analysis of tight junction molecules revealed ADAM15 isoform specific, catalytic function dependent upregulation of Claudin-1. The expression of ADAM15A, and to a lesser degree of C and E isoforms led to an increase in Claudin-1 expression in MDA-MB-231 cells, while ADAM15B had no effect. In MCF-7 cells, ADAM15E was the principal variant inducing Claudin-1 expression. Sh-RNA mediated down-regulation of ADAM15 in ADAM15 over-expressing cells reduced Claudin-1 levels. Additionally, downregulation of endogenous ADAM15 expression in T47D cells by shRNA reduced endogenous Claudin-1 expression confirming a role for ADAM15 in regulating Claudin-1 expression. The PI3K/Akt/mTOR pathway was involved in regulating Claudin-1 expression downstream of ADAM15. Immunofluorescence analysis of MDA-MB-231 ADAM15A expressing cells showed Claudin-1 at cell-cell junctions, in the cytoplasm and nuclei. ADAM15 co-localised with Claudin-1 and ZO1 at cell-cell junctions. Immunoprecipitation analysis demonstrated complex formation between ADAM15 and ZO1/ZO2. These findings highlight the importance of ADAM15 Intra Cellular Domain-mediated interactions in regulating substrate selection and breast cancer cell phenotype