Transcription and Translation Products of the Cytolysin Gene psm-mec on the Mobile Genetic Element SCCmec Regulate Staphylococcus aureus Virulence

The F region downstream of the mecI gene in the SCCmec element in hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) contains two bidirectionally overlapping open reading frames (ORFs), the fudoh ORF and the psm-mec ORF. The psm-mec ORF encodes a cytolysin, phenol-soluble modulin (PSM)-mec. Transformation of the F region into the Newman strain, which is a methicillin-sensitive S. aureus (MSSA) strain, or into the MW2 (USA400) and FRP3757 (USA300) strains, which are community-acquired MRSA (CA-MRSA) strains that lack the F region, attenuated their virulence in a mouse systemic infection model. Introducing the F region to these strains suppressed colony-spreading activity and PSMα production, and promoted biofilm formation. By producing mutations into the psm-mec ORF, we revealed that (i) both the transcription and translation products of the psm-mec ORF suppressed colony-spreading activity and promoted biofilm formation; and (ii) the transcription product of the psm-mec ORF, but not its translation product, decreased PSMα production. These findings suggest that both the psm-mec transcript, acting as a regulatory RNA, and the PSM-mec protein encoded by the gene on the mobile genetic element SCCmec regulate the virulence of Staphylococcus aureus

Validation of a Chinese version of the dental anxiety inventory

Objectives: To translate the English version of Dental Anxiety Inventory (DAxI) and its short-form (SDAxI) and to validate their use in Hong Kong Chinese. Methods: The DAxI and SDAxI were translated into Chinese. A total of 500 adults (18-64 years) were interviewed, the Chinese DAxI, Symptom Checklist 90 (SCL-90), Depression Anxiety Stress Scales (DASS) and State-Trait Anxiety Inventory (STAI) were completed. Based on their initial DAxI scores, 135 interviewees were invited to attend a dental examination 1 month later. Then, the subjects completed the DAxI again, together with Beck Anxiety Inventory (BAI) which measured the state anxiety level of the participants. Two months after the initial interview, all 500 subjects were asked to complete the DAxI again. Another 300 adults were recruited and interviewed for the SDAxI validation. Results: Cronbach's alpha of the Chinese DAxI and SDAxI were 0.77 and 0.80 and the test-retest correlation coefficients were 0.90 and 0.84, respectively. High correlation between BAI and DAxI scores and its stability over time supported construct validity of the Chinese DAxI. Small positive correlations between the DAxI and other subscales of the SCL-90, DASS and STAI supported discriminant validity of the instrument. The SDAxI demonstrated comparable validity and reliability with DAxI. Conclusion: The translated Chinese DAxI demonstrated good validity and reliability. It is available for use in dental anxiety research in adult Chinese. In situations where a short-form is desirable, the Chinese SDAxI is a simple, valid, reliable and interpretable scale for measuring dental anxiety in both research and dental practice. © Blackwell Munksgaard, 2005.postprin

An enigma: Barriers to the identification of students who are gifted with a learning disability

This chapter discusses research that sought to understand the barriers to the identification of students who are gifted with a learning disability (GLD). These students are an enigma within schools and are under-represented in programmes for gifted students. A mixed method of research was used for this research, consisting of two phases that ran concurrently. In Phase 1, teachers from a Sydney Education area were surveyed. In addition, eight of the teachers were interviewed. For Phase 2, multiple case studies were undertaken. The participants were students who were identified as GLD, their families and the professionals they had consulted. The results showed that an identification protocol is needed, as well as teacher training and support from decision makers across all sectors of education. The teachers demonstrated some knowledge with regard to these students but also confusion and conflict with respect to their educational needs

DPYD*6 plays an important role in fluoropyrimidine toxicity in addition to DPYD*2A and c.2846A>T: a comprehensive analysis in 1254 patients

Dihydropyrimidine dehydrogenase (DPYD) is a highly polymorphic gene and classic deficient variants (i.e., c.1236G>A/HapB3, c.1679T>G, c.1905+1G>A and c.2846A>T) are characterized by impaired enzyme activity and risk of severe adverse drug reactions (ADRs) in patients treated with fluoropyrimidines. The identification of poor metabolizers by pre-emptive DPYD screening may reduce the rate of ADRs but many patients with wild-type genotype for classic variants may still display ADRs. Therefore, the search for additional DPYD polymorphisms associated with ADRs may improve the safety of treatment with fluoropyrimidines. This study included 1254 patients treated with fluoropyrimidine-containing regimens and divided into cohort 1, which included 982 subjects suffering from gastrointestinal G≥2 and/or hematological G≥3 ADRs, and cohort 2 (control group), which comprised 272 subjects not requiring dose reduction, delay or discontinuation of treatment. Both groups were screened for DPYD variants c.496A>G, c.1236G>A/HapB3, c.1601G>A (DPYD*4), c.1627A>G (DPYD*5), c.1679T>G (DPYD*13), c.1896T>C, c.1905 + 1G>A (DPYD*2A), c.2194G>A (DPYD*6), and c.2846A>T to assess their association with toxicity. Genetic analysis in the two cohorts were done by Real-Time PCR of DNA extracted from 3 ml of whole blood. DPYD c.496A>G, c.1601G>A, c.1627A>G, c.1896T>C, and c.2194G>A variants were found in both cohort 1 and 2, while c.1905+1G>A and c.2846A>T were present only in cohort 1. DPYD c.1679T>G and c.1236G>A/HapB3 were not found. Univariate analysis allowed the selection of c.1905+1G>A, c.2194G>A and c.2846A>T alleles as significantly associated with gastrointestinal and hematological ADRs (p < 0.05), while the c.496A>G variant showed a positive trend of association with neutropenia (p = 0.06). In conclusion, c.2194G>A is associated with clinically-relevant ADRs in addition to the already known c.1905+1G>A and c.2846A>T variants and should be evaluated pre-emptively to reduce the risk of fluoropyrimidine-associated ADRs