Hypertension

This publication does not have an abstract. The Introduction is displayed as the abstract. Hypertension is known to be a major risk factor for coronary artery disease, heart failure, renal disease and stroke and studies have demonstrated that approximately 20% of the world's population may be affected. In Australia, like other westernised countries, the prevalence of hypertension is higher, with estimates suggesting that 29% of the Australian population is affected and 15% being untreated. In future years, the worldwide incidence of hypertension is expected to increase, due mainly to the effects of an increasingly ageing population and also the westernisation of lifestyles in developing countries. It is assumed that this adopted 'westernised lifestyle' will encourage associated increases in obesity, reduced physical exercise and increased dietary salt intake in those countries. For many years the diagnosis and management of hypertension has been an important issue for primary healthcare providers, as it is a known modifiable risk factor for cardiovascular disease and the associated morbidity, mortality and economic burden of those diseases. It is also recognised that hypertension is often poorly or under treated, and that compliance and persistence with antihypertensive medication is often poor. Over the past two decades there have been regular reviews and revisions of the management guidelines for this condition with most recent discussions centring around a reappraisal of the role of beta blockers. New National Heart Foundation of Australia (NHF) guidelinas for the management of hypertension have recently been released, as have National Institute for Health and Clinical Excellence (NICE) guidelines in the UK. This article is a brief review of the current management guidelines for hypertension with a discussion of the reasoning behind the recent changes

Stochastic noise and synchronisation during Dictyostelium aggregation make cAMP oscillations robust

The molecular network, which underlies the oscillations in the concentration of adenosine 3′, 5′-cyclic monophosphate (cAMP) during the aggregation phase of starvation-induced development in Dictyostelium discoideum, achieves remarkable levels of robust performance in the face of environmental variations and cellular heterogeneity. However, the reasons for this robustness remain poorly understood. Tools and concepts from the field of control engineering provide powerful methods for uncovering the mechanisms underlying the robustness of these types of biological systems. Using such methods, two important factors contributing to the robustness of cAMP oscillations in Dictyostelium are revealed. First, stochastic fluctuations in the molecular interactions of the intracellular network, arising from random or directional noise and biological sources, play an important role in preserving stable oscillations in the face of variations in the kinetics of the network. Second, synchronisation of the aggregating cells through the diffusion of extracellular cAMP appears to be a key factor in ensuring robustness to cell-to-cell variations of the oscillatory waves of cAMP observed in Dictyostelium cell cultures. The conclusions have important general implications for the robustness of oscillating biomolecular networks (whether seen at organism, cell, or intracellular levels and including circadian clocks or Ca2+ oscillations, etc.), and suggest that such analysis can be conducted more reliably by using models including stochastic simulations, even in the case where molecular concentrations are very high

Elucidating the mechanisms of cooperative calcium-calmodulin interactions: a structural systems biology approach

BACKGROUND: Calmodulin is an important multifunctional molecule that regulates the activities of a large number of proteins in the cell. Calcium binding induces conformational transitions in calmodulin that make it specifically active to particular target proteins. The precise mechanisms underlying calcium binding to calmodulin are still, however, quite poorly understood. RESULTS: In this study, we adopt a structural systems biology approach and develop a mathematical model to investigate various types of cooperative calcium-calmodulin interactions. We compare the predictions of our analysis with physiological dose-response curves taken from the literature, in order to provide a quantitative comparison of the effects of different mechanisms of cooperativity on calcium-calmodulin interactions. The results of our analysis reduce the gap between current understanding of intracellular calmodulin function at the structural level and physiological calcium-dependent calmodulin target activation experiments. CONCLUSION: Our model predicts that the specificity and selectivity of CaM target regulation is likely to be due to the following factors: variations in the target-specific Ca2+ dissociation and cooperatively effected dissociation constants, and variations in the number of Ca2+ ions required to bind CaM for target activation

Crosstalk between G-protein and Ca2+ pathways switches intracellular cAMP levels

Cyclic adenosine monophosphate and cyclic guanosine monophosphate are universal intracellular messengers whose concentrations are regulated by molecular networks comprised of different isoforms of the synthases adenylate cyclase or guanylate cyclase and the phosphodiesterases which degrade these compounds. In this paper, we employ a systems biology approach to develop mathematical models of these networks that, for the first time, take into account the different biochemical properties of the isoforms involved. To investigate the mechanisms underlying the joint regulation of cAMP and cGMP, we apply our models to analyse the regulation of cilia beat frequency in Paramecium by Ca(2+). Based on our analysis of these models, we propose that the diversity of isoform combinations that occurs in living cells provides an explanation for the huge variety of intracellular processes that are dependent on these networks. The inclusion of both G-protein receptor and Ca(2+)-dependent regulation of AC in our models allows us to propose a new explanation for the switching properties of G-protein subunits involved in nucleotide regulation. Analysis of the models suggests that, depending on whether the G-protein subunit is bound to AC, Ca(2+) can either activate or inhibit AC in a concentration-dependent manner. The resulting analysis provides an explanation for previous experimental results that showed that alterations in Ca(2+) concentrations can either increase or decrease cilia beat frequency over particular Ca(2+) concentration ranges

Computational modelling suggests dynamic interactions between Ca2+, IP3 and G protein-coupled modules are key to robust Dictyostelium aggregation

Under conditions of starvation, Dictyostelium cells begin a programme of development during which they aggregate to form a multicellular structure by chemotaxis, guided by propagating waves of cyclic AMP that are relayed robustly from cell to cell. In this paper, we develop and analyse a new model for the intracellular and extracellular cAMP dependent processes that regulate Dictyostelium migration. The model allows, for the first time, a quantitative analysis of the dynamic interactions between calcium, IP(3) and G protein-dependent modules that are shown to be key to the generation of robust cAMP oscillations in Dictyostelium cells. The model provides a mechanistic explanation for the transient increase in cytosolic free Ca(2+) concentration seen in recent experiments with the application of the calmodulin inhibitor calmidazolium (R24571) to Dictyostelium cells, and also allows elucidation of the effects of varying both the conductivity of stretch-activated channels and the concentration of external phosphodiesterase on the oscillatory regime of an individual cell. A rigorous analysis of the robustness of the new model shows that interactions between the different modules significantly reduce the sensitivity of the resulting cAMP oscillations to variations in the kinetics of different Dictyostelium cells, an essential requirement for the generation of the spatially and temporally synchronised chemoattractant cAMP waves that guide Dictyostelium aggregation

Educator development and quality assurance: design and evaluation of a pharmacist tutor training programme for enhanced links with pharmacy practice

Background: The involvement of practising pharmacists as sessional tutors provides a number of benefits for a pharmacy programme, including their unique role in bridging the theory-practice gap and ensuring the currency and relevance of the pharmacy curriculum. However, their lack of training and support has been highlighted over recent years (Knott et al., 2015). Objectives: To design and evaluate a pharmacy-specific tutor training programme for pharmacist tutors at James Cook University, based on their needs. Methodology: A needs analysis study involving key stakeholders was conducted which informed the design of the tutor training programme. The programme was evaluated in terms of tutor confidence and competence using two post-training self-evaluation surveys. Descriptive statistics and qualitative thematic analysis were used to analyse the survey data. Results: The training programme was very well received, with 83% of tutors agreeing that the programme was relevant to their current needs. Tutors also reported improvements in both confidence and competence in all areas, particularly in assessment and marking skills. Other benefits highlighted by tutors included better role clarification, improved teaching consistency and the acknowledgement of tutors as an integral part of the pharmacy programme. Discussion: The contribution of sessional staff such as pharmacist tutors at universities has long been underrecognised and undervalued (Ryan et al., 2013). This training programme has not only improved tutor confidence and competence but has also facilitated improved communication and networking between academic staff and practising pharmacists. This has the potential to strengthen the link between academia and pharmacy practice and support a seamless transition from university to the workplace

A systems approach to the perception of the integration of public health into pharmacy practice: A qualitative study

Background: Pharmacists, as health professionals, are ideally positioned to support the health and wellbeing of populations, in addition to their role of providing individualised health care. Objective: The aim of this study was to explore current opinion on the contribution of pharmacists to public health and how this may be enhanced to positively impact public health indicators. Methods: A total of 24 pharmacists from Australia, United Kingdom, Canada and the United States of America, and Australian public health professionals and consumers participated in semi-structured interviews between January and October 2021. Interpretive thematic analysis was applied with coding of transcripts using the constant comparison method. Themes were developed and named in accordance with Bronfenbrenner’s ecological theory of development. Results: Pharmacists contribute to public health and have important roles in health education and illness prevention services. Strong enablers in community pharmacy include trust by consumers and ease of accessibility to pharmacists. Pharmacists are viewed as leaders in communities and contribute to the health system broadly in areas such as medication policy and public health organisations. Participants suggested that pharmacist contributions to public health are often unrecognized by the pharmacy profession, health professionals and consumers, and could be developed to allow effective contributions. Strategies to improve pharmacist contributions included clarifying public health-related terminology, increased development of pharmacy roles and reform for community pharmacies to participate in health prevention and promotion services. Integration of public health in pharmacy education, professional development, and recognition of pharmacy roles across all system levels were also identified as important. Conclusions: The study indicated that pharmacists currently contribute to the improvement of public health. However, development strategies are required for this to be more effective in integrating public health approaches into their professional practice to be recognized for their public health-related roles

Australian pharmacists' perceptions and practices in travel health

Worldwide, pharmacists are playing an increasing role in travel health, although legislation and funding can dictate the nature of this role, which varies from country to country. The aim of this study was to explore the current and potential future practices in travel health for pharmacists in Australia, as well as the perceived barriers, including training needs, for the provision of services. A survey was developed and participation was sought from a representative sample of Australian pharmacists, with descriptive statistics calculated to summarise the frequency of responses. A total of 255 participants, predominantly female (69%), below 50 years (75%) and registered less than 30 years completed the survey. Although over two-thirds (68%) provided travel-related advice in their current practice, the frequency of advice provision was low (less than 2 travellers per week) and limited to responding to travellers questions. Although Australian pharmacists are currently unable to administer travel vaccines and prescription only medications without prescription, they still consider travel health to be an appropriate role and that their clients would seek travel health advice from pharmacies if offered. Currently, key roles for Australian pharmacists are advising travellers who do not seek advice from other practitioners, reinforcing the advice of other health practitioners and referring travellers needing vaccinations and antimalarials. In order to expand these services, the barriers of workload, time, staffing and the need for training in travel health need to be addressed. In summary, the travel health services provided by pharmacies in Australia still have a way to go before they match the services offered by pharmacies in some other countries, however Australian pharmacist are keen to further develop their role in this area

Knowledge, attitudes, and practices of Australian oncology health professionals on complementary medicines

Background: Approximately half of people with cancer are using complementary and alternative medicine (CAM), presenting safety concerns due to potential interactions with conventional cancer treatment. Oncology staff have a role to play in ensuring the safe use of CAMs and so, this study examined their knowledge, attitudes, and practices regarding CAMs. Aim: This study aimed to assess the knowledge, attitudes, and practices of Australian doctors, nurses, and pharmacists regarding CAM use in oncology. Method: Members of three national oncology professional associations took part in an online questionnaire, which determined their knowledge, attitudes, and practices regarding CAM. Results: Ninety-nine completed surveys were obtained from nine doctors, 70 nurses, and 20 pharmacists. Most respondents (68.4%) felt that they did not have adequate knowledge of CAMs to respond to patients' questions. Assessment of attitudes found respondents generally believed that CAMs have a complementary role in oncology but indicated their concerns for the safety of patients. Respondents indicated in practice they would discuss CAMs with less than half of patients (40.6%), with a lack of scientific data and guidelines for CAM use presenting significant barriers to these discussions. Conclusion: Our study suggests that oncology health professionals' knowledge of CAMs potentially leads to a lack of confidence in providing advice to patients and concerns for patient safety. This impacts their discussion of CAMs and lack of disclosure from patients about their use of CAMs. Education on CAMs in oncology would assist in increasing professionals' confidence in discussing these therapies, leading to increased patient disclosure of CAMs and safer treatment decision making for people with cancer