Relevance of the deletion polymorphisms of the glutathione S-transferases GSTT1 and GSTM1 in pharmacology and toxicology

Although cytosolic glutathione S-transferase (GST) enzymes occupy a key position in biological detoxification processes, two of the most relevant human isoenzymes, GSTT1-1 and GSTM1-1, are genetically deleted (non-functional alleles GSTT1*0 and GSTM1*0) in a high percentage of the human population, with major ethnic differences. The structures of the GSTT and GSTM gene areas explain the underlying genetic processes. GSTT1-1 is highly conserved during evolution and plays a major role in phase-II biotransformation of a number of drugs and industrial chemicals, e.g. cytostatic drugs, hydrocarbons and halogenated hydrocarbons. GSTM1-1 is particularly relevant in the deactivation of carcinogenic intermediates of polycyclic aromatic hydrocarbons. Several lines of evidence suggest that hGSTT1-1 and/or hGSTM1-1 play a role in the deactivation of reactive oxygen species that are likely to be involved in cellular processes of inflammation, ageing and degenerative diseases. There is cumulating evidence that combinations of the GSTM1*0 state with other genetic traits affecting the metabolism of carcinogens (CYP1A1, GSTP1) may predispose the aero-digestive tract and lung, especially in smokers, to a higher risk of cancer. The GSTM1*0 status appears also associated with a modest increase in the risk of bladder cancer, consistent with a GSTM1 interaction with carcinogenic tobacco smoke constituents. Both human GST deletions, although largely counterbalanced by overlapping substrate affinities within the GST superfamily, have consequences when the organism comes into contact with distinct man-made chemicals. This appears relevant in industrial toxicology and in drug metabolism.

Conjugation of carcinogens by 6 class glutathione S-transferases : mechanisms and relevance to variations in human risk

Conjugation of chemicals with glutathione (GSH) can lead to decreased or increased toxicity. A genetic deficiency in the GSH S-transferase μ class gene M1 has been hypothesized to lead to greater risk of lung cancer in smokers. Recently a gene deletion polymorphism involving the human θ enzyme T1 has been described; the enzyme is present in erythrocytes and can be readily assayed. A rat θ class enzyme, 5-5, has structural and catalytic similarity and the protein was expressed in the Salmonella typhimurium tester strain TA1535. Expression of the cDNA vector increased the mutagenicity of ethylene dibromide and several methylene dihalides. Mutations resulting from the known GSH S-transferase substrate 1,2-epoxy-3-(4′nitrophenoxy)propane were decreased in the presence of the transferase. Expression of transferase 5-5 increased mutations when 1,2,3,4-diepoxybutane (butadiene diepoxide), 4-bromo-1,2-epoxybutane, or 1,3-dichloracetone were added. The latter compound is a model for the putative 1,2-dibromo-3-chloropropane oxidation product 1-bromo-3-chloroacetone. These genotoxicity and genotyping assays may be of use in further studies of the roles of GSH S-transferase θ enzymes in bioactivation and detoxication and any changes in risk due to polymorphism.

Information experience : approaches to theory and practice

The Queensland University of Technology Research Team has recently edited a book on the idea of information experience. Authors from many parts of the world and focussed on many contexts have contributed chapters. The book represents the first attempt to profile and discuss information experience as a research domain and a research object, together with emphasis on different theories and methods being used in workplace, educational and community contexts. In this session members of the editorial team will introduce the book. We anticipate it will be of interest to any information professionals, students or researchers interested in understanding peoples' information experience.

Addressing alcohol related harms within maxillofacial trauma practice

Background A brief intervention, conducted in the acute setting care setting after an alcohol-related injury, has been reported to be highly beneficial in reducing the risk of re-injury and in reducing subsequent level of alcohol consumption. This project aimed to understand Australasian Oral and Maxillofacial Surgeons' attitudes, knowledge and skills in terms of alcohol screening and brief intervention within acute settings for patients admitted with facial trauma. Materials and Methods A web-based survey was made available to all members (n=200-250) of the Australian and New Zealand Association of Oral and Maxillofacial Surgeons (ANZAOMS), promoted through a number of email bulletins sent by the Association to all members. Implied consent is assumed for participants who complete the online survey. The survey explored their current level of involvement in treating patients with alcohol-relatd facial trauma, as well as their knowledge of and attitudes towards alcohol screening and brief intervention. The survey also explored their willingness for further training and involvement in implementing a SBI program. Parts of the survey were based on a hypothetical case with facial injury and drinking history which was presented to the participants and the participants were asked to give their response to this scenario. Results A total of 58 surgeons completed the on-line survey. 91% of surgeons surveyed were males and 88% were consultant surgeons. 71% would take alcohol history; 29% would deliver a brief alcohol intervention and 14% would refer the patients to an alcohol treatment service or clinician. 40% agreed to have adequate training in managing patients with alcohol-related injuries, while 17% and 19% felt they had adequate time and resources. 76% of surgeons reported the need for more information on where to refer patients for appropriate alcohol treatment. Conclusion The study findings confirm the challenges and barriers to implementing brief alcohol intervention in current practice. There are service gaps that exist, as well as opportunities for training.

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.

Implementation of sustainable evidence-based practice for the assessment and management of pain in residential aged care facilities

Pain is common in residential aged care facilities (RACFs). In 2005, the Australian Pain Society developed 27 recommendations for good practice in the identification, assessment, and management of pain in these settings. This study aimed to address implementation of the standards and evaluate outcomes. Five facilities in Australia participated in a comprehensive evaluation of RACF pain practice and outcomes. Pre-existing pain management practices were compared with the 27 recommendations, before an evidence-based pain management program was introduced that included training and education for staff and revised in-house pain-management procedures. Post-implementation audits evaluated the program's success. Aged care staff teams also were assessed on their reports of self-efficacy in pain management. The results show that before the implementation program, the RACFs demonstrated full compliance on 6 to 12 standards. By the project's completion, RACFs demonstrated full compliance with 10 to 23 standards and major improvements toward compliance in the remaining standards. After implementation, the staff also reported better understanding of the standards (p < .001) or of facility pain management guidelines (p < .001), increased confidence in therapies for pain management (p < .001), and increased confidence in their training to assess pain (p < .001) and recognize pain in residents with dementia who are nonverbal (p = .003). The results show that improved evidence-based practice in RACFs can be achieved with appropriate training and education. Investing resources in the aged care workforce via this implementation program has shown improvements in staff self-efficacy and practice.

An evidence-based program to improve analgesic practice and pain outcomes in residential aged care facilities

Pain is common in individuals living in residential aged care facilities (RACFs), and a number of obstacles have been identified as recurring barriers to adequate pain management. To address this, the Australian Pain Society developed 27 recommendations for comprehensive good practice in the identification, assessment, and management of pain. This study reviewed preexisting pain management practice at five Australian RACFs and identified changes needed to implement the recommendations and then implemented an evidence-based program that aimed to facilitate better pain management. The program involved staff training and education and revised in-house pain-management procedures. Reviews occurred before and after the program and included the assessment of 282 residents for analgesic use and pain status. Analgesic use improved after the program (P<.001), with a decrease in residents receiving no analgesics (from 15% to 6%) and an increase in residents receiving around-the-clock plus as-needed analgesics (from 24% to 43%). There were improvements in pain relief for residents with scores indicative of pain, with Abbey pain scale (P=.005), Pain Assessment in Advanced Dementia Scale (P=.001), and Non-communicative Patient's Pain Assessment Instrument scale (P<.001) scores all improving. Although physical function declined as expected, Medical Outcomes Study 36-item Short-Form Survey bodily pain scores also showed improvement (P=.001). Better evidence-based practice and outcomes in RACFs can be achieved with appropriate training and education. Investing resources in the aged care workforce using this program improved analgesic practice and pain relief in participating sites. Further attention to the continued targeted pain management training of aged care staff is likely to improve pain-focused care for residents.

Milling and diffusion extraction : theory and practice

AN ENGINEERING Workshop was held from 21 to 24 November 2006 in Veracruz, Mexico. Forty delegates from 12 countries attended the workshop on theory and practice of milling and diffusion extraction. This report provides a general overview of activities undertaken during that workshop which consisted of five technical sessions over two days with presentations and discussions plus two days of field and factory visits. Topics covered during the technical sessions included: power transmissions, cane preparation, diffusers, mills, and a comparison of milling and diffusion.

Diagnostic potential of saliva : current state and future applications

BACKGROUND: Over the past 10 years, the use of saliva as a diagnostic fluid has gained attention and has become a translational research success story. Some of the current nanotechnologies have been demonstrated to have the analytical sensitivity required for the use of saliva as a diagnostic medium to detect and predict disease progression. However, these technologies have not yet been integrated into current clinical practice and work flow. CONTENT: As a diagnostic fluid, saliva offers advantages over serum because it can be collected noninvasively by individuals with modest training, and it offers a cost-effective approach for the screening of large populations. Gland-specific saliva can also be used for diagnosis of pathology specific to one of the major salivary glands. There is minimal risk of contracting infections during saliva collection, and saliva can be used in clinically challenging situations, such as obtaining samples from children or handicapped or anxious patients, in whom blood sampling could be a difficult act to perform. In this review we highlight the production of and secretion of saliva, the salivary proteome, transportation of biomolecules from blood capillaries to salivary glands, and the diagnostic potential of saliva for use in detection of cardiovascular disease and oral and breast cancers. We also highlight the barriers to application of saliva testing and its advancement in clinical settings. SUMMARY: Saliva has the potential to become a first-line diagnostic sample of choice owing to the advancements in detection technologies coupled with combinations of biomolecules with clinical relevance. (C) 2011 American Association for Clinical Chemistry

NT-ProBNP levels in saliva and its clinical relevance to heart failure

Background: Current blood based diagnostic assays to detect heart failure (HF) have large intra-individual and inter-individual variations which have made it difficult to determine whether the changes in the analyte levels reflect an actual change in disease activity. Human saliva mirrors the body's health and well being and similar to 20% of proteins that are present in blood are also found in saliva. Saliva has numerous advantages over blood as a diagnostic fluid which allows for a non-invasive, simple, and safe sample collection. The aim of our study was to develop an immunoassay to detect NT-proBNP in saliva and to determine if there is a correlation with blood levels. Methods: Saliva samples were collected from healthy volunteers (n = 40) who had no underlying heart conditions and HF patients (n = 45) at rest. Samples were stored at -80 degrees C until analysis. A customised homogeneous sandwich AlphaLISA((R)) immunoassay was used to quantify NT-proBNP levels in saliva. Results: Our NT-proBNP immunoassay was validated against a commercial Roche assay on plasma samples collected from HF patients (n = 37) and the correlation was r(2) = 0.78 (p<0.01, y = 1.705 x +1910.8). The median salivary NT-proBNP levels in the healthy and HF participants were <16 pg/mL and 76.8 pg/mL, respectively. The salivary NT-proBNP immunoassay showed a clinical sensitivity of 82.2% and specificity of 100%, positive predictive value of 100% and negative predictive value of 83.3%, with an overall diagnostic accuracy of 90.6%. Conclusion: We have firstly demonstrated that NT-proBNP can be detected in saliva and that the levels were higher in heart failure patients compared with healthy control subjects. Further studies will be needed to demonstrate the clinical relevance of salivary NT-proBNP in unselected, previously undiagnosed populations.

Diagnostic potential of saliva : state of the art and future applications [Potenziale diagnostico della saliva: stato dell’arte e applicazioni future]

Over the past 10 years, the use of saliva as a diagnostic fluid has gained attention and has become a translational research success story. Some of the current nanotechnologies have been demonstrated to have the analytical sensitivity required for the use of saliva as a diagnostic medium to detect and predict disease progression. However, these technologies have not yet been integrated into current clinical practice and work flow. As a diagnostic fluid, saliva offers advantages over serum because it can be collected noninvasively by individuals with modest training, and it offers a cost-effective approach for the screening of large populations. Gland-specific saliva can also be used for diagnosis of pathology specific to one of the major salivary glands. There is minimal risk of contracting infections during saliva collection, and saliva can be used in clinically challenging situations, such as obtaining samples from children or handicapped or anxious patients, in whom blood sampling could be a difficult act to perform. In this review we highlight the production of and secretion of saliva, the salivary proteome, transportation of biomolecules from blood capillaries to salivary glands, and the diagnostic potential of saliva for use in detection of cardiovascular disease and oral and breast cancers. We also highlight the barriers to application of saliva testing and its advancement in clinical settings. Saliva has the potential to become a first-line diagnostic sample of choice owing to the advancements in detection technologies coupled with combinations of biomolecules with clinical relevance.

On the (ir)relevance of rates of return measures of economic performance to small boats

A common measure of the economic performance of different fleet segments in fisheries is the rate of return on capital. However, in the English Channel (UK), observed changes in the fleet structure are at odds with expectations given the observed rates of return on capital. This disjunction between expected and observed behaviour raises the question as to the appropriateness of rate of return on capital as a measure of economic performance for small boats whose main input is often non-wage labour. In this paper, an alternative performance indicator is developed based on returns on owner-operator labour. This indicator appears to be of more relevance to small scale boats than the traditional returns on capital, and a better indicator of the direction of adjustment in the fishery.

Saliva proteome research: current status and future outlook

Human saliva harbours proteins of clinical relevance and about 30% of blood proteins are also present in saliva. This highlights that saliva can be used for clinical applications just as urine or blood. However, the translation of salivary biomarker discoveries into clinical settings is hampered by the dynamics and complexity of the salivary proteome. This review focuses on the current status of technological developments and achievements relating to approaches for unravelling the human salivary proteome. We discuss the dynamics of the salivary proteome, as well as the importance of sample preparation and processing techniques and their influence on downstream protein applications; post-translational modifications of salivary proteome and protein: protein interactions. In addition, we describe possible enrichment strategies for discerning post-translational modifications of salivary proteins, the potential utility of selected-reaction-monitoring techniques for biomarker discovery and validation, limitations to proteomics and the biomarker challenge and future perspectives. In summary, we provide recommendations for practical saliva sampling, processing and storage conditions to increase the quality of future studies in an emerging field of saliva clinical proteomics. We propose that the advent of technologies allowing sensitive and high throughput proteome-wide analyses, coupled to well-controlled study design, will allow saliva to enter clinical practice as an alternative to blood-based methods due to its simplistic nature of sampling, non-invasiveness, easy of collection and multiple collections by untrained professionals and cost-effective advantages.