End-of-Life Online Health Education Uptake and Usage by Australian Health Professionals: Urban, Rural and Remote Settings

This work is copyrighted. It may be reproduced in whole or in part for research or training purposes, subject to the inclusion of an acknowledgement of the source. It may not be reproduced for commercial use or sale. Reproduction for purposes other than those indicated above requires written permission from the Flinders University Research Centre for Palliative Care, Death & Dying. Contact [email protected] for permissions.Access to skilled end-of-life care is particularly important for those who live in rural and remote areas in Australia given the high levels of chronic disease and higher mortality rates. However, health professionals in rural and remote areas do not always receive adequate training to provide this care due to lack of accessible education. End-of-Life Essentials (EOLE) is a government funded education project which aims to provide free peer-reviewed online education modules and implementation resources on end-of-life care to health professionals in acute hospitals in Australia. In order to understand the uptake and usage of the EOLE education modules, learners’ geographical locations and module completion data from the first year of the program were analysed according to remoteness category. This White Paper outlines and explores the results of the retrospective data analysis conducted in June 2018. Data from learners who registered in the first year of the EOLE program was were extracted, and 4224 learners were included for data analysis. Study findings show that there is a good reach of EOLE to health professionals living in remote and very remote areas. As learners from very remote areas showed the highest proportion of module completion, it suggests the potential benefit of this important online education in providing accessible continuing end-of-life care education for health professionals residing in the most remote parts of Australia

PgtE Enzyme of Salmonella enterica Shares the Similar Biological Roles to Plasminogen Activator (Pla) in Interacting With DEC-205 (CD205), and Enhancing Host Dissemination and Infectivity by Yersinia pestis

Yersinia pestis, the cause of plague, is a newly evolved Gram-negative bacterium. Through the acquisition of the plasminogen activator (Pla), Y. pestis gained the means to rapidly disseminate throughout its mammalian hosts. It was suggested that Y. pestis utilizes Pla to interact with the DEC-205 (CD205) receptor on antigen-presenting cells (APCs) to initiate host dissemination and infection. However, the evolutionary origin of Pla has not been fully elucidated. The PgtE enzyme of Salmonella enterica, involved in host dissemination, shows sequence similarity with the Y. pestis Pla. In this study, we demonstrated that both Escherichia coli K-12 and Y. pestis bacteria expressing the PgtE-protein were able to interact with primary alveolar macrophages and DEC-205-transfected CHO cells. The interaction between PgtE-expressing bacteria and DEC-205-expressing transfectants could be inhibited by the application of an anti-DEC-205 antibody. Moreover, PgtE-expressing Y. pestis partially re-gained the ability to promote host dissemination and infection. In conclusion, the DEC-205-PgtE interaction plays a role in promoting the dissemination and infection of Y. pestis, suggesting that Pla and the PgtE of S. enterica might share a common evolutionary origin.Peer reviewe

Evaluation of an End-of-Life Essentials Online Education Module on Chronic Complex Illness End-of-Life Care

Chronic complex illness/multimorbidity is a leading cause of death worldwide. Many people with chronic complex illnesses die in hospital, with the overall quality of end-of-life care requiring substantial improvement, necessitating an increase in the knowledge of the health professionals caring for them. End-of-Life-Essentials (EOLE) offers online education modules for health professionals working in acute hospitals, including one on chronic complex illness. A quantitative pre–post-evaluation analysis was undertaken on data from learners (n = 1489), who completed a questionnaire related to knowledge gained from module completion between December 2018 and November 2019. A qualitative post-evaluation analysis was also conducted using data on learner responses to a question posed between May and November 2019. Results showed a significant positive impact on learners’ knowledge, skill, attitude, and confidence in providing end-of-life care to patients living with chronic complex illness. The majority (82.9%, n = 900) intended to change their practice after module completion. A total of n = 559 qualitative comments were analysed thematically, with three major themes emerging: Patient centred care and care planning, Discussion of prognosis, and Valued communication skills. This evaluation has demonstrated that healthcare professionals could benefit from this education to improve quality of care of the dying

Association between TLR4 and PTEN Involved in LPS-TLR4 Signaling Response

In this study, we explored the potential mechanisms of how PTEN regulating LPS induced TLR4 signaling pathway. The initial findings from ELISA demonstrate that PTEN influences TNF-α secretion by its lipid phosphatase activity. Subsequently, western blot, immunoprecipitation assay, and immunofluorescence were performed to explore the activation process of PTEN by stimulation with LPS. As early as 20 minutes after LPS stimulation, reduced phosphorylation of PTEN was found obviously. Accordingly, the whole cell-scattered PTEN translocated towards the cell membrane 20 minutes after stimulating with LPS. Moreover, the weak physical association between PTEN and TLR4 in resting RAW264.7 cells increased gradually after the stimulation of LPS. Furthermore, our study showed PTEN decreased LPS-induced Akt activity and upregulated NF-B-dependent gene transcription, identifying indirectly that the PTEN could regulate the activation of NF-B by its downstream Akt kinase. In summary, our study illustrates the potential signal transduction process of PTEN while stimulated by LPS: by increasing the association of TLR4, PTEN recruits to its phosphoinositide substrate PI(3,4,5)P3 located on the cell membrane and exerts its dephosphorylated function and subsequently depresses the activity of downstream molecule Akt and results in activation of NF-B, followed by the secretion of inflammatory mediators TNF-α.Peer Reviewe

Discovery of a highly potent and orally available importin-β1 inhibitor that overcomes enzalutamide-resistance in advanced prostate cancer

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1