Effects of a Fluorescent Myosin Light Chain Phosphatase Inhibitor on Prostate Cancer Cells

Myosin light chain phosphatase (MLCP) is an enzyme important to regulation of cell cycle and motility that is shown to be upregulated in aggressive prostate cancer cells and tissue. We developed a fluorescent small molecule inhibitor of MLCP using structure based design in recombinant protein phosphatase 1C. Several best fit compounds were synthesized and evaluated by their inhibition of MLCP/32P-MLC dephosphorylation, which resulted in the identification of novel MLCP inhibitors. Androgen dependent (AD) and castration resistant prostate cancer cell (CRPC) lines were treated with the lead inhibitor resulting in decreased growth rate, reduced DNA synthesis, and G2/M cell cycle arrest. Moreover, CRPC cell lines showed an increased sensitivity to drug treatment having GI50 values four times lower than the AD prostate cancer cell line. This was reinforced by reduced BrdU DNA incorporation into CRPC cells compared to AD cells. β-actin disruption was also seen at much lower drug concentrations in CR cells which caused a dose dependent reduction in cellular chemotaxis of PC-3 cells. Since there are currently few clinical therapeutics targeting CR prostate cancer, MLCP represents a new target for preclinical and clinical development of new potential therapeutics which inhibit this disease phenotype

Australian community pharmacy services: a survey of what people with chronic conditions and their carers use versus what they consider important

Objective To explore the purpose/s for which people with chronic conditions and their carers use Australian community pharmacies, and compare this to what pharmacy services they consider important, from the perspectives of both consumers and pharmacists. Design An exploratory study involving a survey, which asked participants to indicate the pharmacy services they had ever used, and rate the importance of 22 pharmacy services to them, or the person they care for, or for their consumers if a pharmacist. Setting Four regions of Australia: Logan-Beaudesert and Mt Isa/North West region, Queensland, Northern Rivers, New South Wales, and the Greater Perth area, Western Australia. Participants Surveys were undertaken with 602 consumers and 91 community pharmacists. Results Community pharmacy is predominantly used to obtain advice about medication and whether a doctor's visit is necessary, as well as for monitoring and screening services. Pharmacy services that were patient centric were important, such as individualised medication advice and respectful care, as well as tools or procedures to facilitate streamlined medication access. Less important services included adult vaccinations and health and wellness programmes. Carers identified services that assisted them with their specific role/s to be important. Overall, community pharmacists had a good understanding of the services that were important to people with chronic conditions and their carers. Conclusions People with chronic conditions and their carers not only care about what services are delivered, but how they are delivered; they sought services that generally improved their access to medication and information, but in a way that was patient centred. Ultimately, pharmacists understood the importance of patient-centred care for people with chronic conditions and their carers, perhaps indicating a greater acceptance of integrating patient-centred care into their everyday practice

Stepped fans and facies-equivalent phyllosilicates in Coprates Catena, Mars

Stepped fan deposits and phyllosilicate mineralogies are relatively common features on Mars but have not previously been found in association with each other. Both of these features are widely accepted to be the result of aqueous processes, but the assumed role and nature of any water varies. In this study we have investigated two stepped fan deposits in Coprates Catena, Mars, which have a genetic link to light-toned material that is rich in Fe–Mg phyllosilicate phases. Although of different sizes and in separate, but adjacent, trough-like depressions, we identify similar features at these stepped fans and phyllosilicates that are indicative of similar formation conditions and processes. Our observations of the overall geomorphology, mineralogy and chronology of these features are consistent with a two stage formation process, whereby deposition in the troughs first occurs into shallow standing water or playas, forming fluvial or alluvial fans that terminate in delta deposits and interfinger with interpreted lacustrine facies, with a later period of deposition under sub-aerial conditions, forming alluvial fan deposits. We suggest that the distinctive stepped appearance of these fans is the result of aeolian erosion, and is not a primary depositional feature. This combined formation framework for stepped fans and phyllosilicates can also explain other similar features on Mars, and adds to the growing evidence of fluvial activity in the equatorial region of Mars during the Hesperian and Amazonian

Positioning pharmacists’ roles in primary health care: a discourse analysis of the compensation plan in Alberta, Canada

Abstract Background A comprehensive Compensation Plan for pharmacy services delivered by community pharmacists was implemented in Alberta, Canada in July 2012. Services covered by the Compensation Plan include care planning services, prescribing services such as adapting prescriptions, and administering a drug or publicly-funded vaccine by injection. Understanding how the Compensation Plan was framed and communicated provides insight into the roles of pharmacists and the potential influence of language on the implementation of services covered by the Compensation Plan by Albertan pharmacists. The objective of this study is to examine the positioning of pharmacists’ roles in documents used to communicate the Compensation Plan to Albertan pharmacists and other audiences. Methods Publicly available documents related to the Compensation Plan, such as news releases or reports, published between January 2012 and December 2015 were obtained from websites such as the Government of Alberta, Alberta Blue Cross, the Alberta College of Pharmacists, the Alberta Pharmacists’ Association, and the Blueprint for Pharmacy. Searches of the Canadian Newsstand database and Google identified additional documents. Discourse analysis was performed using social positioning theory to explore how pharmacists’ roles were constructed in communications about the Compensation Plan. Results In total, 65 publicly available documents were included in the analysis. The Compensation Plan was put forward as a framework for payment for professional services and formal legitimization of pharmacists’ changing professional roles. The discourse associated with the Compensation Plan positioned pharmacists’ roles as: (1) expanding to include services such as medication management for chronic diseases, (2) contributing to primary health care by providing access to services such as prescription renewals and immunizations, and (3) collaborating with other health care team members. Pharmacists’ changing roles were positioned in alignment with the aims of primary health care. Conclusions Social positioning theory provides a useful lens to examine the dynamic and evolving roles of pharmacists. This study provides insight into how communications regarding the Compensation Plan in Alberta, Canada positioned pharmacists’ changing roles in the broader context of changes to primary health care delivery. Our findings may be useful for other jurisdictions considering implementation of remunerated clinical services provided by pharmacists