RanGTPase : a candidate for myc-mediated cancer progression

Background Ras-related nuclear protein (Ran) is required for cancer cell survival in vitro and human cancer progression, but the molecular mechanisms are largely unknown. Methods We investigated the effect of the v-myc myelocytomatosis viral oncogene homolog (Myc) on Ran expression by Western blot, chromatin immunoprecipitation, and luciferase reporter assays and the effects of Myc and Ran expression in cancer cells by soft-agar, cell adhesion, and invasion assays. The correlation between Myc and Ran and the association with patient survival were investigated in 14 independent patient cohorts (n = 2430) and analyzed with Spearman's rank correlation and Kaplan-Meier plots coupled with Wilcoxon-Gehan tests, respectively. All statistical tests were two-sided. Results Myc binds to the upstream sequence of Ran and transactivates Ran promoter activity. Overexpression of Myc upregulates Ran expression, whereas knockdown of Myc downregulates Ran expression. Myc or Ran overexpression in breast cancer cells is associated with cancer progression and metastasis. Knockdown of Ran reverses the effect induced by Myc overexpression in breast cancer cells. In clinical data, a positive association between Myc and Ran expression was revealed in 288 breast cancer and 102 lung cancer specimens. Moreover, Ran expression levels differentiate better or poorer survival in Myc overexpressing breast (χ2 = 24.1; relative risk [RR] = 9.1, 95% confidence interval [CI] = 3.3 to 24.7, P <. 001) and lung (χ2 = 6.04; RR = 2.8, 95% CI = 1.2 to 6.3; P =. 01) cancer cohorts. Conclusions Our results suggest that Ran is required for and is a potential therapeutic target of Myc-driven cancer progression in both breast and lung cancers. © 2013 The Author.

Replicating satellite RNA induces sequence-specific DNA methylation and truncated transcripts in plants

Tobacco plants were transformed with a chimeric transgene comprising sequences encoding β-glucuronidase (GUS) and the satellite RNA (satRNA) of cereal yellow dwarf luteovirus. When transgenic plants were infected with potato leafroll luteovirus (PLRV), which replicated the transgene-derived satRNA to a high level, the satellite sequence of the GUS:Sat transgene became densely methylated. Within the satellite region, all 86 cytosines in the upper strand and 73 of the 75 cytosines in the lower strand were either partially or fully methylated. In contrast, very low levels of DNA methylation were detected in the satellite sequence of the transgene in uninfected plants and in the flanking nonsatellite sequences in both infected and uninfected plants. Substantial amounts of truncated GUS:Sat RNA accumulated in the satRNA-replicating plants, and most of the molecules terminated at nucleotides within the first 60 bp of the satellite sequence. Whereas this RNA truncation was associated with high levels of satRNA replication, it appeared to be independent of the levels of DNA methylation in the satellite sequence, suggesting that it is not caused by methylation. All the sequenced GUS:Sat DNA molecules were hypermethylated in plants with replicating satRNA despite the phloem restriction of the helper PLRV. Also, small, sense and antisense ∼22 nt RNAs, derived from the satRNA, were associated with the replicating satellite. These results suggest that the sequence-specific DNA methylation spread into cells in which no satRNA replication occurred and that this was mediated by the spread of unamplified satRNA and/or its associated 22 nt RNA molecules.

Liquid-vapour phase change : nucleate boiling of pure fluid and nanofluid under different gravity levels

This research was a step towards the comprehension of the nano-particles interaction with bubbles created during boiling. It was aimed at solving the controversies of whether the heat transfer is enhanced or deteriorated during the boiling of the nanofluid. Experiments were conducted in normal gravity and reduced gravity environments on-board the European Space Agency Parabolic Flight Program. The local modification of the thermo-physical properties of the fluid and moreover the modification experienced in the liquid microlayer under the growing vapour bubble were the dominant factors in explaining the mechanisms of the boiling behaviour of the nanofluid.

Cloning and characterization of microRNAs from Brassica napus

A library containing approximately 40,000 small RNA sequences was constructed for Brassica napus. Analysis of 3025 sequences obtained from this library resulted in the identification of 11 conserved miRNA families, which were validated by secondary structure prediction using surrounding sequences in the Brassica genome. Two 21 nt small RNA sequences reside within the arm of a pre-miRNA like stem-loop structure, making them likely candidates for novel non-conserved miRNAs in B. napus. Most of the conserved miRNAs were expressed at similar levels in a F1 hybrid B. napus line and its four double haploid progeny that showed marked variations in phenotypes, but many were differentially expressed between B. napus and Arabidopsis. The miR169 family was expressed at high levels in young leaves and stems, but was undetectable in roots and mature leaves, suggesting that miR169 expression is developmentally regulated in B. napus. © 2007 Federation of European Biochemical Societies.

The baby boomers and beyond report : physical activity levels of older Western Australians 2006

Participation in sufficient levels of physical activity provides significant health benefits, particularly in older adults. The monitoring of physical activity levels in the Western Australian population is therefore necessary for developing and implementing strategies and programs for increasing participation. The Premier’s Physical Activity Taskforce (PATF) conducted a survey in 2006 to measure physical activity levels among Western Australian adults to follow-up the 1999 and 2002 state physical activity surveys. There is now widespread agreement that many health problems of older life – including the onset of frailty and disability – can be postponed or delayed by adopting health-enhancing habits such as physical activity. Adults over 65 years are the most rapidly growing age group and will continue to rise as more persons turn 65. If older adults could be encouraged to be more active as they age, frailty and disability associated with falls would be reduced, and function and physical and mental health in older people would be improved thereby reducing the burden of disease and injury. Given that physical inactivity is one of the most important and modifiable risk factors contributing to ill health, particularly for people as they age, the overall aim of this study was to examine patterns of physical activity in those aged 45 years and over – referred to hereafter as baby boomers+ – in more detail.

Fasting increases serum bilirubin levels in clinically normal, healthy males but not females : a retrospective study from phase I clinical trial participants

Aim: To examine if fasting affects serum bilirubin levels in clinical healthy males and females. Methods: We utilised retrospective data from phase 1 clinical trials where blood was collected in either a fed or fasting state at screening and pre-dosing time points and analysed for total bilirubin levels as per standard clinical procedures. Participants were clinically healthy males (n = 105) or females (n = 30) aged 18 to 48 inclusive who participated in a phase 1 clinical trial in 2012 or 2013. Results: We found a statistically significant increase in total serum bilirubin levels in fasting males as compared to non-fasting males. The fasting time correlated positively with increased bilirubin levels. The age of the healthy males did not correlate with their fasting bilirubin level. We found no correlation between fasting and bilirubin levels in clinically normal females. Conclusions: The recruitment and screening of volunteers for a clinical trial is a time-consuming and expensive process. This study clearly demonstrates that testing for serum bilirubin should be conducted on non-fasting male subjects. If fasting is required, then participants should not be excluded from a trial based on an elevated serum bilirubin that is deemed non-clinically significant.

Long non coding RNAs (lncRNAs) are dysregulated in Malignant Pleural Mesothelioma (MPM)

Malignant Pleural Mesothelioma (MPM) is an aggressive cancer that is often diagnosed at an advanced stage and is characterized by a long latency period (20-40 years between initial exposure and diagnosis) and prior exposure to asbestos. Currently accurate diagnosis of MPM is difficult due to the lack of sensitive biomarkers and despite minor improvements in treatment, median survival rates do not exceed 12 months. Accumulating evidence suggests that aberrant expression of long non-coding RNAs (lncRNAs) play an important functional role in cancer biology. LncRNAs are a class of recently discovered non-protein coding RNAs >200 nucleotides in length with a role in regulating transcription. Here we used NCode long noncoding microarrays to identify differentially expressed lncRNAs potentially involved in MPM pathogenesis. High priority candidate lncRNAs were selected on the basis of statistical (P<0.05) and biological significance (>3-fold difference). Expression levels of 9 candidate lncRNAs were technically validated using RT-qPCR, and biologically validated in three independent test sets: (1) 57 archived MPM tissues obtained from extrapleural pneumonectomy patients, (2) 15 cryopreserved MPM and 3 benign pleura, and (3) an extended panel of 10 MPM cell lines. RT-qPCR analysis demonstrated consistent up-regulation of these lncRNAs in independent datasets. ROC curve analysis showed that two candidates were able to separate benign pleura and MPM with high sensitivity and specificity, and were associated with nodal metastases and survival following induction chemotherapy. These results suggest that lncRNAs have potential to serve as biomarkers in MPM.

Levels of social trust among men from refugee backgrounds after the 2011 Queensland floods

Purpose This paper examines the relationship between flood exposure and levels of social trust among a cohort of adult men from refugee backgrounds who were affected by the 2011 Queensland floods in Australia. Design/methodology/approach A quantitative questionnaire was administered to 141 men from refugee backgrounds almost two years after the 2011 Queensland floods. The survey was administered in person by trained peer in-terviewers, and included a number of standardised instruments assessing respondents’ so-cio-demographic characteristics, levels of social trust towards and from neighbours, the police, the wider Australian community, and the media, and exposure to and impact of the floods. Multiple logistic regression analyses were used to assess the relationship between flood exposure and social trust adjusting for pre-disaster levels of trust and other potentially confounding variables. Findings Participants with higher levels of flood exposure were significantly more likely to report greater levels of trust both towards and from their neighbours, the wider Australian community, and the media, and they were also more likely to believe that most people can be trusted. Research limitations/implications Although the study reports on data collected two years after the floods, the analysis has adjusted for pre-disaster measures of social trust and other socio-demographic variables. Originality/value Our paper has highlighted the important place of social trust and social capital for refugee communities in a post-disaster setting. Disaster responses that support social capital among marginalised populations are critical to increasing community resilience and supporting recovery.

Noise levels in a general intensive care unit : a descriptive study.

The aim of this small-scale study was to measure, analyse and compare levels of acoustic noise, in a nine-bedded general intensive care unit (ICU). Measurements were undertaken using the Norsonic 116 sound level meter recording noise levels in the internationally agreed ‘A’ weighted scale. Noise level data were obtained and recorded at 5 min over 3 consecutive days. Results of noise level analysis indicated that mean noise levels within this clinical area was 56·42 dB(A), with acute spikes reaching 80 dB(A). The quietest noise level attained was that of 50 dB(A) during sporadic intervals throughout the 24-h period. Parametric testing using analysis of variance found a positive relationship (p ≤ 0·001) between the nursing shifts and the day of the week. However, Scheffe multiple range testing showed significant differences between the morning shift, and the afternoon and night shifts combined (p ≤ 0·05). There was no statistical difference between the afternoon and night shifts (p ≥ 0·05). While the results of this study may seem self-evident in many respects, what it has highlighted is that the problem of excessive noise exposure within the ICU continues to go unabated. More concerning is that the prolonged effects of excessive noise exposure on patients and staff alike can have deleterious effect on the health and well-being of these individuals.

Noise levels in a General Surgical Ward : a descriptive study

Aims and objectives.  This study was undertaken to measure and analyse levels of acoustic noise in a General Surgical Ward. Method.  Measurements were undertaken using the Norsonic 116 sound level meter (SLM) recording noise levels in the internationally agreed ‘A’ weighted scale. Noise level data and observational data as to the number of staff present were obtained and recorded at 5-min intervals over three consecutive days. Results.  Results of noise level analysis indicated that mean noise level within this clinical area was 42.28 dB with acute spikes reaching 70 dB(A). The lowest noise level attained was that of 36 dB(A) during the period midnight to 7 a.m. Non-parametric testing, using Spearman's Rho (two-tailed), found a positive relationship between the number of staff present and the level of noise recorded, indicating that the presence of hospital personnel strongly influences the level of noise within this area. Relevance to clinical practice.  Whilst the results of this may seem self-evident in many respects the problems of excessive noise production and the exposure to it for patients, hospital personnel and relatives alike continues unabated. What must be of concern is the psychophysiological effects excessive noise exposure has on individuals, for example, decreased wound healing, sleep deprivation and cardiovascular stimulation.

Palliative care provision for patients with a haematological malignancy : can we do more?

This editorial depicts the current challenges in palliative care provision for patients with a haematological malignancy and the contribution of cancer nurses. There have been significant advancements in the care of patients with a hematological malignancy over the past three or more decades1. Despite this, there still exists a significant mortality risk in curative treatment and many patients with a hematological malignancy will die from their disease1. A growing body of research indicates patients with a hematological malignancy do not receive best practice palliative and end-of-life care2. Shortfalls in care include poor referral patterns to specialist palliative care services, lack of honest discussions regarding death and dying, inadequate spiritual care for patients and families, patients frequently dying in the acute care setting and high levels of patient and family distress2. There have been a number of efforts in the United Kingdom, United States of America, Sweden, and Australia demonstrating palliative and hematology care can co-exist, exemplified through clinical case studies and innovative models of care2. However, deficits in the provision of palliative care for patients with a hematological malignancy persist as evident in the international literature2. Addressing this issue requires research exploring new aspects of a complex scenario; here we suggest priority areas of research...

Metal ion levels post primary unilateral Exeter total hip arthroplasty

BACKGROUND: Metal ion release is common following total hip arthroplasty, yet postoperative levels have not been defined for most stems currently used in clinical practice. AIM: To assess metal ion release in the serum of patients with well functioning unilateral Exeter V40 primary total hip arthroplasties one year after surgery. METHODS: Whole blood chromium and serum cobalt levels were measured in 20 patients following primary total hip arthroplasty with the Exeter V40 stem and a variety of acetabular components one year after surgery. RESULTS: Whole blood chromium levels were within the normal range (10-100 nmol/L), with a single mild elevation of serum cobalt (normal < 20 nmol/L). CONCLUSION: In well functioning primary unilateral total hip arthroplasty using the Exeter V40 stem with a variety of acetabular components one year post surgery, whole blood chromium levels are normal and serum cobalt elevations are rare and mild.

Raising levels of awareness of rights and obligations in the provision of financial product advice to retail clients

In September-December 2012, 548 financial planning retail clients and 77 financial advisers responded to online surveys addressing consumer satisfaction with financial planning services and the provision of information concerning regulatory and rights issues. Retail clients commented on areas related to the best interests duty in s 961B of the Corporations Act 2001 (Cth), in particular the extent to which advisers considered their clients’ financial objectives and lifestyle situations, and the client-centredness of the financial advice they received. Retail clients also indicated their level of awareness of their substantive rights in relation to receiving advice, the legal obligations imposed on advisers, and whether they would access internal and external complaints processes if warranted. Advisers reported on the extent to which they provide clients with information relating to their substantive rights, and complaints processes available to them. Responses were analysed in relation to client demographics (e.g., age, gender, education), and experience of financial advice. This article reports on the findings of the surveys and their implications for financial planners.

Cough and exhaled nitric oxide levels : what happens with exercise?

Cough associated with exertion is often used as a surrogate marker of asthma. However, to date there are no studies that have objectively measured cough in association with exercise in children. Our primary aim was to examine whether children with a pre-existing cough have an increase in cough frequency during and post-exercise. We hypothesized that children with any coughing illness will have an increase in cough frequency post-exercise regardless of the presence of exercise-induced broncho-constriction (EIB) or atopy. In addition, we hypothesized that Fractional exhaled nitric oxide (FeNO) levels decreases post-exercise regardless of the presence of EIB or atopy. Children with chronic cough and a control group without cough undertook an exercise challenge, FeNO measurements and a skin prick test, and wore a 24-h voice recorder to objectively measure cough frequency. The association between recorded cough frequency, exercise, atopy, and presence of EIB was tested. We also determined if the change in FeNO post exercise related to atopy or EIB. Of the 50 children recruited (35 with cough, 15 control), 7 had EIB. Children with cough had a significant increase in cough counts (median 7.0, inter-quartile ranges, 0.5, 24.5) compared to controls (2.0, IQR 0, 5.0, p = 0.028) post-exercise. Presence of atopy or EIB did not influence cough frequency. FeNO level was significantly lower post-exercise in both groups but the change was not influenced by atopy or EIB. Cough post-exertion is likely a generic response in children with a current cough. FeNO level decreases post-exercise irrespective of the presence of atopy or EIB. A larger study is necessary confirm or refute our findings.