Epigenetic regulation of chemokine/chemokine receptor expression

Epigenetic regulation of gene expression is an important event for normal cellular homeostasis. Gene expression may be "switched" on or "turned" off via epigenetic means through adjustments in DNA architecture. These structural alterations result from changes to the DNA methylation status in addition to histone posttranslational modifications such as acetylation and methylation. Drugs which can alter the status of these epigenetic markers are currently undergoing clinical trials in a wide variety of diseases, including cancer.We illustrate the treatment of cell lines with histone deacetylase (HDi) and DNA methyltransferase inhibitors and the subsequent RNA isolation and reverse transcriptase polymerase chain reaction for several members of the CXC (ELR(+)) chemokine family. In addition we describe a chromatin immunoprecipitation assay to determine the association between chromatin transcription markers and DNA following pretreatment of cell cultures with an HDi, Trichostatin A (TSA). This assay allows us to determine whether treatment with TSA dynamically remodels the promoter region of our selected genes, as judged by the differences in the PCR product between our treated and untreated samples.

Acquired differential regulation of caspase-8 in cisplatin-resistant non-small-cell lung cancer

Failure to efficiently induce apoptosis contributes to cisplatin resistance in non-small-cell lung cancer (NSCLC). Although BCL-2-associated X protein (BAX) and BCL-2 antagonist killer (BAK) are critical regulators of the mitochondrial apoptosis pathway, their requirement has not been robustly established in relation to cisplatin. Here, we show that cisplatin can efficiently bypass mitochondrial apoptosis block caused by loss of BAX and BAK, via activation of the extrinsic death receptor pathway in some model cell lines. Apoptosis resistance following cisplatin can only be observed when both extrinsic and intrinsic pathways are blocked, consistent with redundancy between mitochondrial and death receptor pathways in cisplatin-induced apoptosis. In H460 NSCLC cells, caspase-8 cleavage was shown to be induced by cisplatin and is dependent on death receptor 4, death receptor 5, Fas-associated protein with death domain, acid sphingomyelinase and ceramide synthesis. In contrast, cisplatin-resistant cells fail to activate caspase-8 via this pathway despite conserving sensitivity to death ligand-driven activation. Accordingly, caspase-8 activation block acquired during cisplatin resistance, can be bypassed by death receptor agonism.

A pilot study exploring Australian general practice nurses roles, responsibilities and professional development needs in well and sick child care

Aim Explore practice nurses' (PNs) role in child health and development, and advising parents about child health issues. Background Introduction of the four-year-old child health check into general practice in 2008 placed additional responsibilities on PNs in child health and wellness. This study explores their readiness to expand their practice into this area. Design Integrated mixed method design, self-report survey. Method A purpose-developed questionnaire explored demographics, child health roles and responsibilities, difficulties encountered, professional development needs, barriers and facilitators, and professional development activities undertaken in the past year. Surveys were posted to 218 PNs in one rural Division of General Practice (DGP) in Queensland, Australia; 29 responded. Results PNs reported a significant role in well and sick child care (93.1%) though few had a paediatric/child health background (14.3%). Roles included immunisations (92.3%), child health checks (65.4%), general child health and development (26.9%), asthma (23.1%), feeding (15.4%), fever (11.5%), settling/sleeping (11.5%). PNs were interested in learning more about (81.5%) and incorporating more child health into their practice (81.5%). Professional development in childhood growth and development (80.0%), health and illness (60.0%) and advising new mothers (20.0%) was needed. Conclusions PNs play a substantial role in child health, are unprepared for the complexities of this role and have preferred methods for undertaking professional development to address knowledge deficits. Implications for practice PNs are unprepared for an advanced role in child health and wellness. Significant gaps in their knowledge to support this role were identified. This ever-expanding role requires close monitoring to ensure knowledge precedes expectations to practice.

Immune regulation during chronic visceral leishmaniasis

Visceral leishmaniasis is a chronic parasitic disease associated with severe immune dysfunction. Treatment options are limited to relatively toxic drugs and there is no vaccine for humans available. Hence, there is an urgent need to better understand immune responses following infection with Leishmania species by studying animal models of disease and clinical samples from patients. Here, we review recent discoveries in these areas and highlight shortcomings in our knowledge that need to be addressed if better treatment options are to be developed and effective vaccines designed.

Expression, regulation and putative nutrient-sensing function of taste GPCRs in the heart

G protein-coupled receptors (GPCRs) are critical for cardiovascular physiology. Cardiac cells express >100 nonchemosensory GPCRs, indicating that important physiological and potential therapeutic targets remain to be discovered. Moreover, there is a growing appreciation that members of the large, distinct taste and odorant GPCR families have specific functions in tissues beyond the oronasal cavity, including in the brain, gastrointestinal tract and respiratory system. To date, these chemosensory GPCRs have not been systematically studied in the heart. We performed RT-qPCR taste receptor screens in rodent and human heart tissues that revealed discrete subsets of type 2 taste receptors (TAS2/Tas2) as well as Tas1r1 and Tas1r3 (comprising the umami receptor) are expressed. These taste GPCRs are present in cultured cardiac myocytes and fibroblasts, and are enriched in myocytes, which we corroborated using in situ hybridization. Tas1r1 gene-targeted mice (Tas1r1Cre/Rosa26tdRFP) strikingly recapitulated these data. In vivo taste receptor expression levels were developmentally regulated in the postnatal period. Intriguingly, several Tas2rs were upregulated in cultured rat myocytes and in mouse heart in vivo following starvation. The discovery of taste GPCRs in the heart opens an exciting new field of cardiac research. We predict that these taste receptors may function as nutrient sensors in the heart.

The ACORN Standards : our aide memoire to professional practice

The Oxford English Dictionary defines a standard as “a required or agreed level of quality or attainment” or “principles of conduct informed by notions of honour and decency”. What does this mean for perioperative nurses? Standards provide minimum requirements for best practice and are regarded as generally accepted principles of patient care and perioperative management. In health care, standards provide a common language and set of expectations that enable health care professionals, systems and organisations to work together for best patient outcomes...

Becoming a pharmacist : the role of curriculum in professional identity formation

Objective To understand how the formal curriculum experience of an Australian undergraduate pharmacy program supports students’ professional identity formation. Methods A qualitative ethnographic study was conducted over four weeks using participant observation and examined the ‘typical’ student experience from the perspective of a pharmacist. A one-week period of observation was undertaken with each of the four year groups (that is, for years one to four) comprising the undergraduate curriculum. Data were collected through observation of the formal curriculum experience using field notes, a reflective journal and informal interviews with 38 pharmacy students. Data were analyzed thematically using an a priori analytical framework. Results Our findings showed that the observed curriculum was a conventional curricular experience which focused on the provision of technical knowledge and provided some opportunities for practical engagement. There were some opportunities for students to imagine themselves as pharmacists, for example, when the lecture content related to practice or teaching staff described their approach to practice problems. However, there were limited opportunities for students to observe pharmacist role models, experiment with being a pharmacist or evaluate their professional identities. While curricular learning activities were available for students to develop as pharmacists e.g. patient counseling, there was no contact with patients and pharmacist academic staff tended to role model as educators with little evidence of their pharmacist selves. Conclusion These findings suggest that the current conventional approach to the curriculum design may not be fully enabling learning experiences which support students in successfully negotiating their professional identities. Instead it appeared to reinforce their identities as students with a naïve understanding of professional practice, making their future transition to professional practice challenging.

School nurses and partnerships for health education : team teaching in the secondary school curricula

The purpose of this research is to examine School Based Youth Health Nurses experience of partnerships for health education and team teaching. The School Based Youth Health Nurse Program is a contemporary model of school nursing in Queensland, Australia. The role of the School Based Youth Health Nurse consists of individual health consultations and health promotion. This research analyses a subset of qualitative data collected for a larger project about the experience of school based youth health nursing. The Health Promoting Schools model is used as a deductive framework. The findings reveal five subthemes across the three areas of the Health Promoting Schools approach. There are two subthemes within the curriculum, teaching and learning area; We were on the same page so to speak and I can go and do my reports or whatever. There are two sub-themes within the partnerships and services area; I had a beautiful science teacher who was just delightful and really just wanted to do things in partnerships and It’s all airy fairy arty farty stuff that’s not important. There is one theme in the school organisation, ethos and environment area; I just don’t know how well the top of these organisations communicate with the bottom of those organisations. Successful partnerships for health education and team teaching between school nurses and teachers are based on personal relationships based on rapport which lead to trust and reciprocity. Partnerships are limited by teachers understanding of the role of the school nurse and engagement with school nurses in the classroom. Administrative support from the top down is fundamental.

Sustaining safety and mobility amongst older adults : the multilevel older driver self-regulation model

This multidisciplinary research advanced the current understanding of self-regulation – a critical component in safe and sustainable mobility for older adults. It investigates the sociodemographic and psychosocial factors that underlies older adults' self-regulation, and examines their travel behaviours using a combination of self-report, in-vehicle and wearable devices. This research developed a novel theoretical model that significantly predicts self-regulation and objectively driving behaviours among older drivers.

Evidence-Based Health Practice

Research is one of the subjects that students in the health professions often find challenging and yet the process of finding, critiquing, using and evaluating information is essential to professional development and practice. This book introduces fundamental research concepts that are relevant to the wider health-care and disability support sector while also making strong connections to the various areas of practice that students identify with.Examples and cases are taken from a wide range of professions and countries to help students understand the significance of research used by colleagues from other disciplines and become interprofessional practitioners.

The importance of social support for students with intellectual disability : an intervention to promote mental health and well-being

Children and adolescents with intellectual disability have higher rates of mental health problems compared with there typically developing peers. Social support has been identified as an important protective factor for psychological well - being. In this paper we discuss the benefits of social support networks, and consider approaches for promoting children’s perceptions of the availability of social support. We describe an evidence-based intervention that has been specially adapted and implemented for students with intellectual disability in school settings. In a randomised controlled trial, the Aussie Optimism Resilience Skills Program was associated with improved perceptions of social support following a 10-week intervention. Educators need to be aware of the increased vulnerability of students with intellectual disability to the development mental health problems and the proactive ways in which they can promote psychological well - being within their classrooms.

The global public health issue of pharmaceutical waste : what role for pharmacists?

Purpose Pharmaceuticals have played an important role in improving the quality of life of the human population in modern times. However, it must also be acknowledged that both the production and use of pharmaceuticals have a significant, negative impact on the environment and consequently, a negative impact on the health of humans and wildlife. This negative impact is due to the embedded carbon in pharmaceuticals' manufacture and distribution and the waste generated in their manufacture, consumption and disposal. Pharmaceutical waste is comprised of contaminated waste (unwanted pharmaceuticals and their original containers) and non-contaminated waste (non-hazardous packaging waste). The paper aims to discuss these issues. Design/methodology/approach The article is a literature review. Findings The article identified a gap in the literature around pharmacist attitudes and behaviour toward the environmentally responsible handling of pharmaceutical waste. Originality/value Pharmacists, with their professional commitment to the quality use of medicines and their active participation in the medicines management pathway, already play an important role in the more sustainable use of pharmaceuticals. Even so, they have the potential to play an even greater role with the environmentally responsible disposal of pharmaceutical waste (including packaging waste) and the education of other health professionals and the general public on this topic.

Expanding horizons : scientific frontiers, legal regulation, and globalization

In the six decades since the discovery of the double helix structure of DNA by Watson and Crick in 1953, developments in genetic science have transformed our understanding of human health and disease. These developments, along with those in other areas such as computer science, biotechnology, and nanotechnology, have opened exciting new possibilities for the future. In addition, the increasing trend for technologies to converge and build upon each other potentially increases the pace of change, constantly expanding the boundaries of the scientific frontier. At the same time, however, scientific advances are often accompanied by public unease over the potential for unforeseen, negative outcomes. For governments, these issues present significant challenges for effective regulation. This Article analyzes the challenges associated with crafting laws for rapidly changing science and technology. It considers whether we need to regulate, how best to regulate for converging technologies, and how best to ensure the continued relevance of laws in the face of change.

Registration of clinical trials: Challenges for global regulation

In 2004 the International Committee of Medical Journal Editors (ICMJE) issued a statement indicating that from 1 July 2005 registration in a publicly accessible trials registry would be a condition of publication in an ICMJE member journal. The World Health Organisation is coordinating the International Clinical Trials Registry Platform (ICTRP) as a means of providing a standardised framework for registration. This article considers the practical challenges and opportunities that arise from these developments and considers the relevance of trial registration for women and minorities and for developing countries.