Molecular characterization of endocarditis-associated Staphylococcus aureus

Infective endocarditis (IE) is a life-threatening infection of the heart endothelium and valves. Staphylococcus aureus is a predominant cause of severe IE and is frequently associated with infections in health care settings and device-related infections. Multilocus sequence typing (MLST), spa typing, and virulence gene microarrays are frequently used to classify S. aureus clinical isolates. This study examined the utility of these typing tools to investigate S. aureus epidemiology associated with IE. Ninety-seven S. aureus isolates were collected from patients diagnosed with (i) IE, (ii) bloodstream infection related to medical devices, (iii) bloodstream infection not related to medical devices, and (iv) skin or soft-tissue infections. The MLST clonal complex (CC) for each isolate was determined and compared to the CCs of members of the S. aureus population by eBURST analysis. The spa type of all isolates was also determined. A null model was used to determine correlations of IE with CC and spa type. DNA microarray analysis was performed, and a permutational analysis of multivariate variance (PERMANOVA) and principal coordinates analysis were conducted to identify genotypic differences between IE and non-IE strains. CC12, CC20, and spa type t160 were significantly associated with IE S. aureus. A subset of virulence-associated genes and alleles, including genes encoding staphylococcal superantigen-like proteins, fibrinogen-binding protein, and a leukocidin subunit, also significantly correlated with IE isolates. MLST, spa typing, and microarray analysis are promising tools for monitoring S. aureus epidemiology associated with IE. Further research to determine a role for the S. aureus IE-associated virulence genes identified in this study is warranted.

Occupational and non-occupational risk factors in bladder cancer patients in an industrialized area located in former East-Germany [Berufliche und außerberufliche Risikofaktoren für das Harnblasenkarzinom in einem ehemaligen Industriegebiet der neuen Bundesländer]

Purpose: Several occupational carcinogens are metabolized by polymorphic enzymes. The distribution of the polymorphic enzymes N-acetyltransferase 2 (NAT2; substrates: aromatic amines), glutathione S-transferase M1 (GSTM1; substrates: e.g., reactive metabolites of polycyclic aromatic hydrocarbons), and glutathione S-transferase T1 (GSTT1; substrates: small molecules with 1-2 carbon atoms) were investigated. Material and Methods: At the urological department in Lutherstadt Wittenberg, 136 patients with a histologically proven transitional cell cancer of the urinary bladder were investigated for all occupations performed for more than 6 months. Several occupational and non-occupational risk factors were asked. The genotypes of NAT2, GSTM1, and GSTT1 were determined from leucocyte DNA by PCR. Results: Compared to the general population in Middle Europe, the percentage of GSTT1 negative persons (22.1 %) was ordinary; the percentage of slow acetylators (59.6%) was in the upper normal range, while the percentage of GSTM1 negative persons (58.8%) was elevated in the entire group. Shifts in the distribution of the genotypes were observed in subgroups who had been exposed to asbestos (6/6 GSTM1 negative, 5/6 slow acetylators), rubber manufacturing (8/10 GSTM1 negative), and chlorinated solvents (9/15 GSTM1 negative). Conclusions: The overrepresentation of GSTM1 negative bladder cancer patients also in this industrialized area and more pronounced in several occupationally exposed subgroups points to an impact of the GSTM1 negative genotype in bladder carcinogenesis. [Article in German]

Interactions of ingested food, beverage, and tobacco components involving human cytochrome P4501A2, 2A6, 2E1, and 3A4 enzymes

Human cytochrome P450 (P450) enzymes are involved in the oxidation of natural products found in foods, beverages, and tobacco products and their catalytic activities can also be modulated by components of the materials. The microsomal activation of aflatoxin B1 to the exo-3,9-epoxide is stimulated by flavone and 7,8-benzoflavone, and attenuated by the flavonoid naringenin, a major component of grapefruit. P4502E1 has been demonstrated to play a potentially major role in the activation of a number of very low-molecular weight cancer suspects, including ethyl carbamate (urethan), which is present in alcoholic beverages and particularly stone brandies. The enzyme (P4502E1) is also known to be inducible by ethanol. Tobacco contains a large number of potential carcinogens. In human liver microsomes a significant role for P4501A2 can be demonstrated in the activation of cigarette smoke condensate. Some of the genotoxicity may be due to arylamines. P4501A2 is also inhibited by components of crude cigarette smoke condensate. The tobacco-specific nitrosamines are activated by a number of P450 enzymes. Of those known to be present in human liver, P4501A2, 2A6, and 2E1 can activate these nitrosamines to genotoxic products.

Keeping our nursing and midwifery workforce : factors that support non-practising clinicians to return to practice

BACKGROUND: Within Australia and internationally (Health Workforce Australia, 2012) an increasing and on-going nursing workforce shortage is documented. Recent international estimates indicate that there will be ongoing and significant gaps in the supply of a nursing workforce; the United Kingdom is predicted to have a reduction of 12.12% nurses over the coming eight years if a current 'steady state' is maintained (Buchan and Seacombe, 2011); Canada is predicted to have a shortage of 60,000 nurses by 2022 (Tomblin et al., 2012) with Australia's anticipated nursing shortage reported as over 90,000 by the year 2025 (Health Workforce Australia, 2012). Queensland Health in response to their tracked emerging nursing and midwifery workforce shortages developed a nursing and midwifery refresher programme to return registered staff back to the workforce. A study was undertaken between 2008 and 2010 to provide an understanding of how non-practising nurses and midwives maybe supported back into the workforce. METHODS: Programme applicants (444) were invited to respond to an on-line survey designed to understand what aspects of the programme supported their learning and ability to return to the workforce. This number represents those who applied but not all completed or commenced the programme. Descriptive statistics (Polit and Beck, 2008) were used to collate quantifiable survey responses and free text and unsolicited responses were themed. RESULTS: The survey received a 35.5% response rate (n=158) with a return of 20% of unsolicited comments in the form of e-mail responses which were included in the themed results. Key themes supporting participants' learning and ability to return to the workforce were: Respondents were 94% female and 6% male, with 37.7% >51 years of age. Child rearing was the foremost reason for female staff relinquishing workforce roles (36.6%). The primary reason for returning to the workforce was maintenance of registration (40.5%). Both theory and clinical placement components were seen by participants as contributing to their confidence to return to the health workforce. CONCLUSION: The Queensland Nursing and Midwifery Refresher Programs provided a structured programme for registered, non-practising nurses and midwives to return to the Queensland Health workforce. Responses indicated that clinical supervision and contract learning should be central to a return to workforce induction programme for registered but non-practising nurses and midwives. The majority of nurses and midwives returning to the workforce were approaching retirement age in 10-15 years.

Incidence of paediatric fatal and non-fatal low speed vehicle run over events in Queensland, Australia : eleven year analysis

Background The purpose of this study was to estimate the incidence of fatal and non-fatal Low Speed Vehicle Run Over (LSVRO) events among children aged 0–15 years in Queensland, Australia, at a population level. Methods Fatal and non-fatal LSVRO events that occurred in children resident in Queensland over eleven calendar years (1999-2009) were identified using ICD codes, text description, word searches and medical notes clarification, obtained from five health related data bases across the continuum of care (pre-hospital to fatality). Data were manually linked. Population data provided by the Australian Bureau of Statistics were used to calculate crude incidence rates for fatal and non-fatal LSVRO events. Results There were 1611 LSVROs between 1999–2009 (IR = 16.87/100,000/annum). Incidence of non-fatal events (IR = 16.60/100,000/annum) was 61.5 times higher than fatal events (IR = 0.27/100,000/annum). LSVRO events were more common in boys (IR = 20.97/100,000/annum) than girls (IR = 12.55/100,000/annum), and among younger children aged 0–4 years (IR = 21.45/100000/annum; 39% or all events) than older children (5–9 years: IR = 16.47/100,000/annum; 10–15 years IR = 13.59/100,000/annum). A total of 896 (56.8%) children were admitted to hospital for 24 hours of more following an LSVRO event (IR = 9.38/100,000/annum). Total LSVROs increased from 1999 (IR = 14.79/100,000) to 2009 (IR = 18.56/100,000), but not significantly. Over the 11 year period, there was a slight (non –significant) increase in fatalities (IR = 0.37-0.42/100,000/annum); a significant decrease in admissions (IR = 12.39–5.36/100,000/annum), and significant increase in non-admissions (IR = 2.02-12.77/100,000/annum). Trends over time differed by age, gender and severity. Conclusion This is the most comprehensive, population-based epidemiological study on fatal and non-fatal LSVRO events to date. Results from this study indicate that LSVROs incur a substantial burden. Further research is required on the characteristics and risk factors associated with these events, in order to adequately inform injury prevention. Strategies are urgently required in order to prevent these events, especially among young children aged 0-4 years.

2nd ESMO consensus conference on lung cancer : early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, earlystage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on early-stage disease. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

2nd ESMO Consensus Conference on Lung Cancer : non-small-cell lung cancer first-line/second and further lines in advanced disease

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, early stage disease and locally-advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on 1st line / 2nd and further lines of treatment in advanced disease. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Relationship between EGFR expression, EGFR mutation status, and the efficacy of chemotherapy plus cetuximab in FLEX study patients with advanced non-small-cell lung cancer

INTRODUCTION: The phase III FLEX study (NCT00148798) in advanced non-small-cell lung cancer indicated that the survival benefit associated with the addition of cetuximab to cisplatin and vinorelbine was limited to patients whose tumors expressed high levels of epidermal growth factor receptor (EGFR) (immunohistochemistry score of >/=200; scale 0-300). We assessed whether the treatment effect was also modulated in FLEX study patients by tumor EGFR mutation status. METHODS: A tumor mutation screen of EGFR exons 18 to 21 included 971 of 1125 (86%) FLEX study patients. Treatment outcome in low and high EGFR expression groups was analyzed across efficacy endpoints according to tumor EGFR mutation status. RESULTS: Mutations in EGFR exons 18 to 21 were detected in 133 of 971 tumors (14%), 970 of which were also evaluable for EGFR expression level. The most common mutations were exon 19 deletions and L858R (124 of 133 patients; 93%). In the high EGFR expression group (immunohistochemistry score of >/=200), a survival benefit for the addition of cetuximab to chemotherapy was demonstrated in patients with EGFR wild-type (including T790M mutant) tumors. Although patient numbers were small, those in the high EGFR expression group whose tumors carried EGFR mutations may also have derived a survival benefit from the addition of cetuximab to chemotherapy. Response data suggested a cetuximab benefit in the high EGFR expression group regardless of EGFR mutation status. CONCLUSIONS: The survival benefit associated with the addition of cetuximab to first-line chemotherapy for advanced non-small-cell lung cancer expressing high levels of EGFR is not limited by EGFR mutation status.

Second ESMO consensus conference on lung cancer : pathology and molecular biomarkers for non-small-cell lung cancer

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The Second ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on management of patients with nonsmall- cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, early stage disease, locally advanced disease and advanced (metastatic) disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on recommendations for pathology and molecular biomarkers in relation to the diagnosis of lung cancer, primarily non-small-cell carcinomas.

Tailored silica coated Ag nanoparticles for non-invasive surface enhanced Raman spectroscopy of biomolecular targets

Silica coated Ag nanoparticles with defined surface plasmon resonances are used to selectively detect and analyze protein cofactors in solution and on interfaces via surface enhanced resonance Raman spectroscopy. The silica coating has a surprisingly small effect on optical amplification but minimizes unwanted interactions between the protein and the nanoparticle.