Targeting oxidative stress in cancer

Importance of the field: Reactive oxygen species (ROS) occur as natural by-products of oxygen metabolism and have important cellular functions. Normally, the cell is able to maintain an adequate balance between the formation and removal of ROS either via anti-oxidants or through the use specific enzymatic pathways. However, if this balance is disturbed, oxidative stress may occur in the cell, a situation linked to the pathogenesis of many diseases, including cancer. Areas covered in this review: HDACs are important regulators of many oxidative stress pathways including those involved with both sensing and coordinating the cellular response to oxidative stress. In particular aberrant regulation of these pathways by histone deacetylases may play critical roles in cancer progression. What the reader will gain: In this review we discuss the notion that targeting HDACs may be a useful therapeutic avenue in the treatment of oxidative stress in cancer, using chronic obstructive pulmonary disease (COPD), NSCLC and hepatocellular carcinoma (HCC) as examples to illustrate this possibility. Take home message: Epigenetic mechanisms may be an important new therapeutic avenue for targeting oxidative stress in cancer. © 2010 Informa UK, Ltd.

Monitoring and benchmarking government policies and actions to improve the healthiness of food environments : a proposed Government Healthy Food Environment Policy Index

Government action is essential to increase the healthiness of food environments and reduce obesity, diet-related non-communicable diseases (NCDs), and their related inequalities. This paper proposes a monitoring framework to assess government policies and actions for creating healthy food environments. Recommendations from relevant authoritative organizations and expert advisory groups for reducing obesity and NCDs were examined, and pertinent components were incorporated into a comprehensive framework for monitoring government policies and actions. A Government Healthy Food Environment Policy Index (Food-EPI) was developed, which comprises a ‘policy’ component with seven domains on specific aspects of food environments, and an ‘infrastructure support’ component with seven domains to strengthen systems to prevent obesity and NCDs. These were revised through a week-long consultation process with international experts. Examples of good practice statements are proposed within each domain, and these will evolve into benchmarks established by governments at the forefront of creating and implementing food policies for good health. A rating process is proposed to assess a government's level of policy implementation towards good practice. The Food-EPI will be pre-tested and piloted in countries of varying size and income levels. The benchmarking of government policy implementation has the potential to catalyse greater action to reduce obesity and NCDs.

Interpersonal, intrapersonal, extrapersonal? Qualitatively investigating coordinative couplings between rowers in Olympic sculling

Coordinative couplings are commonly classified as interpersonal and intrapersonal. Interpersonal coordination is normally thought of as between organisms but a subset can also be considered where the co-actors movements are coupled to an environmental rhythm. This can be termed extrapersonal coordination. This study explores how coordination is achieved in a situation that demands that at least one actor makes use of extrapersonal sources. In this case multi-seat rowing, where one actor cannot see the other one behind them. A qualitative approach using experiential knowledge from expert rowers (N=9) and coaches (N=4) was used to examine how interpersonal coordination was achieved and maintained in 2 person rowing boats. It was reported that where possible, both rowers coordinated their movements by coupling with an invariant provided by the boat. This invariant is underpinned by perception of water flow past the boat; which is in turn used to determine changes in acceleration - 'rowing with the boat.' Bow seat also identified the rower in front and stroke seat identified the looming of the stern as viable alternative sources for coupling.

Cardiac safety concerns for ondansetron, an antiemetic commonly used for nausea linked to cancer treatment and following anaesthesia

Introduction: Ondansetron is a 5-HT3 receptor antagonist commonly used as an anti-emetic to prevent the nausea and vomiting associated with anti-cancer drugs, cancer radiotherapy, or postoperatively. Recently, the US Food and Drug Administration (FDA) issued a warning for ondansetron due to a potential for prolongation of the QT interval of the electrocardiogram (ECG), a phenomenon that is associated with an increased risk of the potentially fatal arrhythmia torsade de pointes. Areas covered: We undertook a review of the cardiac safety of ondansetron. Our primary sources of information were PubMed (with downloading of full articles), and the internet. Expert opinion: The dose of ondansetron that the FDA has concerns about is 32 mg iv (or several doses that are equivalent to this), which is only used in preventing nausea and vomiting associated with cancer chemotherapy. This suggests that ondansetron may be safe in the lower doses used to prevent the nausea and vomiting in radiation treatment or postoperatively. However, as there is a report that a lower dose of ondansetron prolonged the QT interval in healthy volunteers, this needs to be clarified by the FDA. More research needs to be undertaken of the relationship between QT prolongation and torsades in order that the FDA can produce clear-cut evidence of pro-arrhythmic risk when introducing warnings for this.

Percutaneous coronary intervention with drug-eluting stents or coronary artery bypass surgery in subjects with type 2 diabetes : evaluation of: Farkouth ME, Domanski M, Sleeper LA, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med 2012;367(25):2375-84, and Contini GA, Nicolini F, Fortuna D, et al. Five-year outcomes of surgical or percutaneous myocardial revascularization in diabetic patients. Int J Cardiol 2012. [Epub ahead of print]

There is debate as to whether percutaneous coronary intervention (PCI) with drug-eluting stents or coronary artery bypass surgery (CABG) is the best procedure for subjects with type 2 diabetes and coronary artery disease requiring revascularization. There is some evidence that following these procedures there is less further revascularization with CABG than PCI in subjects with diabetes. Two recent studies; the FREEDOM (Future Revascularization Evaluation in patients with Diabetes mellitus: Optimal Management of Multivessel Disease) trial, and a trial using a real world diabetic population from a Registry, have shown that the benefits of CABG over PCI in subjects with type 2 diabetes extends to lower rates of death and myocardial infarct, in addition to lower rates of revascularization. However, the rates of stroke may be higher with CABG than PCI with drug-eluting stents in this population. Thus, if CABG is going to be preferred to PCI in subjects with type 2 diabetes and multivessel coronary disease, consideration should be given to how to reduce the rates of stroke with CABG.

Cardiac safety concerns for domperidone, an antiemetic and prokinetic, and galactogogue medicine

Introduction: Domperidone is a dopamine D2-receptor antagonist developed as an antiemetic and prokinetic agents. Oral domperidone is not approved in the US, but is used in many countries to treat nausea and vomiting, gastroparesis, and as a galactogogue (to promote lactation). The US Food and Drug Administration (FDA) have issued a warning about the cardiac safety of domperidone. Areas covered: The authors undertook a review of the cardiac safety of oral domperidone. Expert opinion: The data from preclinical studies are unambiguous in identifying domperidone as able to produce marked hERG channel inhibition and action potential prolongation at clinically relevant concentrations. The compound’s propensity to augment instability of action potential duration and action potential triangulation are also indicative of proarrhythmic potential. Domperidone should not be administered to subjects with pre-existing QT prolongation/LQTS, subjects receiving drugs that inhibit CYP3A4, subjects with electrolyte abnormalities or with other risk factors for QT-prolongation. With these provisos, it is possible that domperidone may be used as a galactogogue without direct risk to healthy breast feeding women but more safety information should be sought in this situation. Also, more safety information is required regarding risk to breast feeding infants or before domperidone is routinely used in gastroparesis or gastroesphageal reflux in children.

Developing an evidence-based clinical pathway for the assessment, diagnosis and management of acute Charcot Neuro-Arthropathy : a systematic review

Background: Charcot Neuro-Arthropathy (CN) is one of the more devastating complications of diabetes. To the best of the authors' knowledge, it appears that no clinical tools based on a systematic review of existing literature have been developed to manage acute CN. Thus, the aim of this paper was to systematically review existing literature and develop an evidence-based clinical pathway for the assessment, diagnosis and management of acute CN in patients with diabetes. Methods: Electronic databases (Medline, PubMed, CINAHL, Embase and Cochrane Library), reference lists, and relevant key websites were systematically searched for literature discussing the assessment, diagnosis and/or management of acute CN published between 2002-2012. At least two independent investigators then quality rated and graded the evidence of each included paper. Consistent recommendations emanating from the included papers were then fashioned in a clinical pathway. Results: The systematic search identified 267 manuscripts, of which 117 (44%) met the inclusion criteria for this study. Most manuscripts discussing the assessment, diagnosis and/or management of acute CN constituted level IV (case series) or EO (expert opinion) evidence. The included literature was used to develop an evidence-based clinical pathway for the assessment, investigations, diagnosis and management of acute CN. Conclusions: This research has assisted in developing a comprehensive, evidence-based clinical pathway to promote consistent and optimal practice in the assessment, diagnosis and management of acute CN. The pathway aims to support health professionals in making early diagnosis and providing appropriate immediate management of acute CN, ultimately reducing its associated complications such as amputations and hospitalisations.

Is the clinical Queensland High Risk Foot Form valid or reliable for research?

Background High-risk foot complications such as neuropathy, ischaemia, deformity, infections, ulcers and amputations consume considerable health care resources and typically result from chronic diseases. This study aimed to develop and test the validity and reliability of a Queensland High Risk Foot Form (QHRFF) tool. Methods Phase one involved developing a QHRFF using an existing diabetes high-risk foot tool, literature search, expert panel and several state-wide stakeholder groups. Phase two tested the criterion-related validity along with inter- and intra-rater reliability of the final QHRFF. Three cohorts of patients (n = 94) and four clinicians, representing different levels of expertise, were recruited. Validity was determined by calculating sensitivity, specificity and positive predictive values (PPV). Kappa and intra-class correlation (ICC) statistics were used to establish reliability. Results A QHRFF tool containing 46-items across seven domains was developed and endorsed. The majority of QHRFF items achieved moderate-to-perfect validity (PPV = 0.71 – 1) and reliability (Kappa/ICC = 0.41 – 1). Items with weak validity and/or reliability included those identifying health professionals previously attending the patient, other (non-listed) co-morbidity, previous foot ulcer, foot deformity, optimum offloading and optimum footwear. Conclusions The QHRFF had moderate-to-perfect validity and reliability across the majority of items, particularly identifying individual co-morbidities and foot complications. Items with weak validity or reliability need to be re-defined or removed. Overall, the QHRFF appears to be a valid and reliable tool to assess, collect and measure clinical data pertaining to high-risk foot complications for clinical or research purposes.

Experience of being an advanced practice nurse within Australian acute care settings : a systematic review of qualitative evidence

Background Nationally and internationally, advanced practice nurses are working under various titles and in different contexts to address gaps within healthcare systems. Analysis of advanced practice roles in different countries has been undertaken, but due to variations in cultural, geographical and professional factors, it is difficult and perhaps ineffectual to compare roles between countries. Contextual factors may also affect the actual experience of being an advanced practice nurse. A systematic review was therefore undertaken of qualitative evidence on the experience of being an advanced practice nurse in Australia, to provide deeper understanding of the role in the defined context. Methods The review followed the method for qualitative synthesis as per the Joanna Briggs Institute. An extensive search was undertaken of databases and online resources to find published and unpublished studies. Papers from 1990 to October 2011 which met specified inclusion criteria were appraised using the Joanna Briggs Institute Qualitative Assessment and Review Instrument. Results Three published studies and one unpublished dissertation were included in the review. From these studies, 216 findings were extracted and these were formed into 18 categories. Six meta-syntheses grouped under the headings of expert knowledge, confidence, education, relationships, negative experiences and patient-centred experience were created. Organisational factors impact greatly on the experience, professionally and personally. Conclusions Heterogeneity of role titles makes synthesis a difficult process, but contextualising the population provides a pragmatic approach to informing the status of the advanced practice nurse discourse. The review identifies positive and negative experiences of being an advanced practice nurse in Australian acute care settings with overlapping and intertwining findings that reinforce the complexity of the role.

Urinary biomarkers of physical activity : candidates and clinical utility

Chronic physical inactivity is a major risk factor for a number of important lifestyle diseases, while inappropriate exposure to high physical demands is a risk factor for musculoskeletal injury and fatigue. Proteomic and metabolomic investigations of the physical activity continuum - extreme sedentariness to extremes in physical performance - offer increasing insight into the biological impacts of physical activity. Moreover, biomarkers, revealed in such studies, may have utility in the monitoring of metabolic and musculoskeletal health or recovery following injury. As a diagnostic matrix, urine is non-invasive to collect and it contains many biomolecules, which reflect both positive and negative adaptations to physical activity exposure. This review examines the utility and landscape of biomarkers of physical activity with particular reference to those found in urine.

Bearing Fault Diagnostics Using the Spectral Pattern Recognition

In the field of diagnostics of rolling element bearings, the development of sophisticated techniques, such as Spectral Kurtosis and 2nd Order Cyclostationarity, extended the capability of expert users to identify not only the presence, but also the location of the damage in the bearing. Most of the signal-analysis methods, as the ones previously mentioned, result in a spectrum-like diagram that presents line frequencies or peaks in the neighbourhood of some theoretical characteristic frequencies, in case of damage. These frequencies depend only on damage position, bearing geometry and rotational speed. The major improvement in this field would be the development of algorithms with high degree of automation. This paper aims at this important objective, by discussing for the first time how these peaks can draw away from the theoretical expected frequencies as a function of different working conditions, i.e. speed, torque and lubrication. After providing a brief description of the peak-patterns associated with each type of damage, this paper shows the typical magnitudes of the deviations from the theoretical expected frequencies. The last part of the study presents some remarks about increasing the reliability of the automatic algorithm. The research is based on experimental data obtained by using artificially damaged bearings installed in a gearbox.

Swimmer localization from a moving camera

At the highest level of competitive sport, nearly all performances of athletes (both training and competitive) are chronicled using video. Video is then often viewed by expert coaches/analysts who then manually label important performance indicators to gauge performance. Stroke-rate and pacing are important performance measures in swimming, and these are previously digitised manually by a human. This is problematic as annotating large volumes of video can be costly, and time-consuming. Further, since it is difficult to accurately estimate the position of the swimmer at each frame, measures such as stroke rate are generally aggregated over an entire swimming lap. Vision-based techniques which can automatically, objectively and reliably track the swimmer and their location can potentially solve these issues and allow for large-scale analysis of a swimmer across many videos. However, the aquatic environment is challenging due to fluctuations in scene from splashes, reflections and because swimmers are frequently submerged at different points in a race. In this paper, we temporally segment races into distinct and sequential states, and propose a multimodal approach which employs individual detectors tuned to each race state. Our approach allows the swimmer to be located and tracked smoothly in each frame despite a diverse range of constraints. We test our approach on a video dataset compiled at the 2012 Australian Short Course Swimming Championships.

Motivating domestic energy conservation through comparative feedback in mobile applications and social networking sites

The progress of technology has led to the increased adoption of energy monitors among household energy consumers. While the monitors available on the market deliver real-time energy usage feedback to the consumer, the form of this data is usually unengaging and mundane. Moreover, it fails to address consumers with different motivations and needs to save and compare energy. This master‟s thesis project presents a study that seeks to inform design guidelines for differently motivated energy consumers. The focus of the research is on comparative feedback supported by a community of energy consumers. In particular, the discussed comparative feedback types are explanatory comparison, temporal self-comparison, norm comparison, one-on-one comparison and ranking, whereby the last three support exploring the potential of socialising energy-related feedback in social networking sites, such as Facebook. These feedback types were integrated in EnergyWiz – a mobile application that enables users to compare with their past performance, neighbours, contacts from social networking sites and other EnergyWiz users. The application was developed through a theory-driven approach and evaluated in personal, semi-structured interviews which provided insights on how motivation-related comparative feedback should be designed. It was also employed in expert focus group discussions which resulted in defining opportunities and challenges before mobile, social energy monitors. The findings have unequivocally shown that users with different motivations to compare and to conserve energy have different preferences for comparative feedback types and design. It was established that one of the most influential factors determining design factors is the people users compare to. In addition, the research found that even simple communication strategies in Facebook, such as wall posts and groups can contribute to engagement with energy conservation practices. The concept of mobility of the application was evaluated as positive since it provides place and time-independent access to the energy consumption data.