55 research outputs found

    Systematic review of factors affecting transition readiness skills in patients with inflammatory bowel disease.

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    BACKGROUND AND AIMS: The incidence of inflammatory bowel disease (IBD) diagnosed before adulthood is increasing worldwide. Transition from paediatric to adult healthcare requires certain skills. The aim of this study was to identify factors affecting these skills. METHODS: This review was registered on the PROSPERO database (CRD42019152272). Inclusion criteria: 1) studies of factors affecting transition readiness skills in patients with IBD 2) written in English 3) published since 1999. MEDLINE, CINAHL and PsychINFO databases were searched between 1999-2019. Quality was assessed using the Joanna Briggs Institute critical appraisal tools. RESULTS: Searches identified 822 papers. Sixteen papers were included. Age was positively associated with skills including disease knowledge and performing self-management behaviours (14 studies). Improvement often occurs at 18, however, skill deficiency may still remain. Increased self-efficacy (confidence) was associated with greater disease knowledge and performing self-management behaviours (3 studies). Self-efficacy was positively correlated with transition duration (2 studies) and health-related quality of life (r=0.57, p<0.001) (1 study), negatively correlated with depression (r=-0.57, p<0.001) and anxiety (r=-0.23, p=0.03) (1 study), and associated with higher education level (2 studies) and a family history of IBD (1 study). Females had higher self-management scores (3 studies), and greater healthcare satisfaction was significantly associated with higher knowledge (1 study). Greater transition communication improved knowledge, self-management, and overall transition readiness (2 studies). CONCLUSIONS: Potentially modifiable factors have been identified that could be supported in the transitioning IBD population to improve transition readiness. Identification of those with non-modifiable characteristics associated with poor readiness may aid targeted support

    Dynamic Changes in Brain Functional Connectivity during Concurrent Dual-Task Performance

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    This study investigated the spatial, spectral, temporal and functional proprieties of functional brain connections involved in the concurrent execution of unrelated visual perception and working memory tasks. Electroencephalography data was analysed using a novel data-driven approach assessing source coherence at the whole-brain level. Three connections in the beta-band (18–24 Hz) and one in the gamma-band (30–40 Hz) were modulated by dual-task performance. Beta-coherence increased within two dorsofrontal-occipital connections in dual-task conditions compared to the single-task condition, with the highest coherence seen during low working memory load trials. In contrast, beta-coherence in a prefrontal-occipital functional connection and gamma-coherence in an inferior frontal-occipitoparietal connection was not affected by the addition of the second task and only showed elevated coherence under high working memory load. Analysis of coherence as a function of time suggested that the dorsofrontal-occipital beta-connections were relevant to working memory maintenance, while the prefrontal-occipital beta-connection and the inferior frontal-occipitoparietal gamma-connection were involved in top-down control of concurrent visual processing. The fact that increased coherence in the gamma-connection, from low to high working memory load, was negatively correlated with faster reaction time on the perception task supports this interpretation. Together, these results demonstrate that dual-task demands trigger non-linear changes in functional interactions between frontal-executive and occipitoparietal-perceptual cortices

    Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes

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    BACKGROUND: Olaparib (Lynparza™) is a PARP inhibitor approved for advanced BRCA-mutated (BRCAm) ovarian cancer. PARP inhibitors may benefit patients whose tumours are dysfunctional in DNA repair mechanisms unrelated to BRCA1/2. We report exploratory analyses, including the long-term outcome of candidate biomarkers of sensitivity to olaparib in BRCA wild-type (BRCAwt) tumours. METHODS: Tumour samples from an olaparib maintenance monotherapy trial (Study 19, D0810C00019; NCT00753545) were analysed. Analyses included classification of mutations in genes involved in homologous recombination repair (HRR), BRCA1 promoter methylation status, measurement of BRCA1 protein and Myriad HRD score. RESULTS: Patients with BRCAm tumours gained most benefit from olaparib; a similar treatment benefit was also observed in 21/95 patients whose tumours were BRCAwt but had loss-of-function HRR mutations compared to patients with no detectable HRR mutations (58/95). A higher median Myriad MyChoice® HRD score was observed in BRCAm and BRCAwt tumours with BRCA1 methylation. Patients without BRCAm tumours derived benefit from olaparib treatment vs placebo although to a lesser extent than BRCAm patients.CONCLUSIONS: Ovarian cancer patients with tumours harbouring loss-of-function mutations in HRR genes other than BRCA1/2 may constitute a small, molecularly identifiable and clinically relevant population who derive treatment benefit from olaparib similar to patients with BRCAm

    The Staphylococcus aureus Response to Unsaturated Long Chain Free Fatty Acids: Survival Mechanisms and Virulence Implications

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    Staphylococcus aureus is an important human commensal and opportunistic pathogen responsible for a wide range of infections. Long chain unsaturated free fatty acids represent a barrier to colonisation and infection by S. aureus and act as an antimicrobial component of the innate immune system where they are found on epithelial surfaces and in abscesses. Despite many contradictory reports, the precise anti-staphylococcal mode of action of free fatty acids remains undetermined. In this study, transcriptional (microarrays and qRT-PCR) and translational (proteomics) analyses were applied to ascertain the response of S. aureus to a range of free fatty acids. An increase in expression of the σB and CtsR stress response regulons was observed. This included increased expression of genes associated with staphyloxanthin synthesis, which has been linked to membrane stabilisation. Similarly, up-regulation of genes involved in capsule formation was recorded as were significant changes in the expression of genes associated with peptidoglycan synthesis and regulation. Overall, alterations were recorded predominantly in pathways involved in cellular energetics. In addition, sensitivity to linoleic acid of a range of defined (sigB, arcA, sasF, sarA, agr, crtM) and transposon-derived mutants (vraE, SAR2632) was determined. Taken together, these data indicate a common mode of action for long chain unsaturated fatty acids that involves disruption of the cell membrane, leading to interference with energy production within the bacterial cell. Contrary to data reported for other strains, the clinically important EMRSA-16 strain MRSA252 used in this study showed an increase in expression of the important virulence regulator RNAIII following all of the treatment conditions tested. An adaptive response by S. aureus of reducing cell surface hydrophobicity was also observed. Two fatty acid sensitive mutants created during this study were also shown to diplay altered pathogenesis as assessed by a murine arthritis model. Differences in the prevalence and clinical importance of S. aureus strains might partly be explained by their responses to antimicrobial fatty acids

    Questioning evidence of group selection in spiders

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    Any field study showing convincing evidence of group selection would be a significant contribution to the field of evolutionary biology. Pruitt and Goodnight1 claim to provide such evidence in a 14–18-month field experiment on spiders. However, we contend that apparent flaws in their predictions, assumptions, methods and interpretations undermine this claim. We believe that the data presented are unreliable and are equally consistent with both group selection and individual-level selection; thus, we question the conclusion of Pruitt and Goodnight1 that group selection has produced the observed patterns
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