Phenotypic screening, transcriptional profiling, and comparative genomic analysis of an invasive and non-invasive strain of Candida albicans

<p>Abstract</p> <p>Background</p> <p>Invasion of host tissue by the human fungal pathogen <it>Candida albicans </it>is an important step during the development of candidosis. However, not all <it>C. albicans </it>strains possess the same invasive and virulence properties. For example, the two clinical isolates SC5314 and ATCC10231 differ in their ability to invade host tissue and cause experimental infections. Strain SC5314 is invasive whereas strain ATCC10231 is non-invasive and strongly attenuated in virulence compared to SC5314. In this study we compare the <it>in vitro </it>phenotypic, transcriptional and genomic profiles of these two widely used laboratory strains in order to determine the principal biological and genetic properties responsible for their differential virulence.</p> <p>Results</p> <p>In all media tested, the two strains showed the same metabolic flexibility, stress resistance, adhesion properties and hydrolytic enzyme secretion <it>in vitro</it>. However, differences were observed in response to cell-surface disturbing agents and alkaline pH. Furthermore, reduced hyphal formation in strain ATCC10231 under certain conditions correlated with reduced invasive properties in an <it>in vitro </it>invasion assay and a reduced ability to invade epithelial tissue. Despite these diverse phenotypic properties, no substantial genomic differences were detected by comparative genome hybridisation within the open reading frames. However, <it>in vitro </it>transcriptional profiling displayed major differences in the gene expression of these two strains, even under normal <it>in vitro </it>growth conditions.</p> <p>Conclusion</p> <p>Our data suggest that the reason for differential virulence of <it>C. albicans </it>strains is not due to the absence of specific genes, but rather due to differences in the expression, function or activity of common genes.</p

Making hard choices easier: a prospective, multicentre study to assess the efficacy of a fertility-related decision aid in young women with early-stage breast cancer

BACKGROUND: Fertility is a priority for many young women with breast cancer. Women need to be informed about interventions to retain fertility before chemotherapy so as to make good quality decisions. This study aimed to prospectively evaluate the efficacy of a fertility-related decision aid (DA). METHODS: A total of 120 newly diagnosed early-stage breast cancer patients from 19 Australian oncology clinics, aged 18–40 years and desired future fertility, were assessed on decisional conflict, knowledge, decision regret, and satisfaction about fertility-related treatment decisions. These were measured at baseline, 1 and 12 months, and were examined using linear mixed effects models. RESULTS: Compared with usual care, women who received the DA had reduced decisional conflict (β=−1.51; 95%CI: −2.54 to 0.48; P=0.004) and improved knowledge (β=0.09; 95%CI: 0.01–0.16; P=0.02), after adjusting for education, desire for children and baseline uncertainty. The DA was associated with reduced decisional regret at 1 year (β=−3.73; 95%CI: −7.12 to −0.35; P=0.031), after adjusting for education. Women who received the DA were more satisfied with the information received on the impact of cancer treatment on fertility (P<0.001), fertility options (P=0.005), and rated it more helpful (P=0.002), than those who received standard care. CONCLUSION: These findings support widespread use of this DA shortly after diagnosis (before chemotherapy) among younger breast cancer patients who have not completed their families

Prevalence and clinical and psychological correlates of high fear of cancer recurrence in patients newly diagnosed with head and neck cancer

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Measuring Metacognition in Cancer: Validation of the Metacognitions Questionnaire 30 (MCQ-30)

Objective The Metacognitions Questionnaire 30 assesses metacognitive beliefs and processes which are central to the metacognitive model of emotional disorder. As recent studies have begun to explore the utility of this model for understanding emotional distress after cancer diagnosis, it is important also to assess the validity of the Metacognitions Questionnaire 30 for use in cancer populations. Methods 229 patients with primary breast or prostate cancer completed the Metacognitions Questionnaire 30 and the Hospital Anxiety and Depression Scale pre-treatment and again 12 months later. The structure and validity of the Metacognitions Questionnaire 30 were assessed using factor analyses and structural equation modelling. Results Confirmatory and exploratory factor analyses provided evidence supporting the validity of the previously published 5-factor structure of the Metacognitions Questionnaire 30. Specifically, both pre-treatment and 12 months later, this solution provided the best fit to the data and all items loaded on their expected factors. Structural equation modelling indicated that two dimensions of metacognition (positive and negative beliefs about worry) were significantly associated with anxiety and depression as predicted, providing further evidence of validity. Conclusions These findings provide initial evidence that the Metacognitions Questionnaire 30 is a valid measure for use in cancer populations

Unidimensional scales for fears of cancer recurrence and their psychometric properties : the FCR4 and FCR7

Funding: Support was received from SUPAC (NCRI) Early Career Fund to complete this study. NCRI Supportive & Palliative Care (SuPaC) Research Collaboratives Capacity Building Grant Scheme: G Ozakinci (PI), G Humphris, M Sharpe.Background:  The assessment of fear of recurrence (FCR) is crucial for understanding an important psychological state in patients diagnosed and treated for cancer. The study aim was to determine psychometric details of a seven question self-report scale (FCR7) and a short form (FCR4) based upon items already used in various extensive measures of FCR. Methods:  Two consecutive samples of patients (breast and colorectal) were recruited from a single specialist cancer centre. The survey instrument contained the FCR7 items, Hospital Anxiety and Depression Scale (HADS), and demographic details. Clinical information was obtained from patient hospital records. Statistical analyses were performed using classical test and item response theory approaches, to demonstrate unidimensional factor structure and testing key parameters. Construct validity was inspected through nomological and theoretical prediction. Results:  Internal consistency was demonstrated by alpha coefficients (FCR4: 0.93 and FCR7: 0.92). Both scales (FCR7 & FCR4) were associated with the HADs subscales as predicted. Patients who experienced chemotherapy, minor aches/pains, thought avoidance of cancer and high cancer risk belief were more fearful. Detailed inspection of item responses profile provided some support for measurement properties of scales. Conclusion: The internal consistency, and pattern of key associations and discriminability indices provided positive psychometric evidence for these scales. The brief measures of FCR may be considered for audit, screening or routine use in clinical service and research investigations.Publisher PDFPeer reviewe

Hsp21potentiates antifungal drug tolerance in Candida albicans

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