Conscientious objection - a cross-sectional, vignette-based, mixed methods exploration of Australian pharmacists' perspectives.

Background: Conscientious objection (CO) in healthcare is a controversial topic. Some perceive CO as freedom of conscience, others believe their professional duty-of-care overrides personal-perspectives. There is a paucity of literature pertaining to pharmacists' perspectives on CO. Aim: To explore Australian pharmacists' decision-making in complex scenarios around CO and reasons for their choices. Method: A cross-sectional, qualitative questionnaire of pharmacists' perspectives on CO. Vignette-based questions were about scenarios related to medical termination, emergency contraception, IVF surrogacy for a same-sex couple and Voluntary Assisted Dying (VAD) Results: Approximately half of participants (n = 223) believed pharmacists have the right to CO and most agreed to supply prescriptions across all vignettes. However, those who chose not to supply (n = 20.9%), believed it justifiable, even at the risk of patients failing to access treatment. Strong self-reported religiosity had a statistically significant relationship with decisions not to supply for 3 of 4 vignettes. Three emergent themes included: ethical considerations, the role of the pharmacist and training and guidance. Conclusion: This exploratory study revealed perspectives of Australian pharmacists about a lack of guidance around CO in pharmacy. Findings highlighted the need for future research to investigate and develop further training and professional frameworks articulating steps to guide pharmacists around CO.

PEGylated nanoparticles interact with macrophages independently of immune response factors and trigger a non-phagocytic, low-inflammatory response.

Poly-ethylene-glycol (PEG)-based nanoparticles (NPs) - including cylindrical micelles (CNPs), spherical micelles (SNPs), and PEGylated liposomes (PLs) - are hypothesized to be cleared in vivo by opsonization followed by liver macrophage phagocytosis. This hypothesis has been used to explain the rapid and significant localization of NPs to the liver after administration into the mammalian vasculature. Here, we show that the opsonization-phagocytosis nexus is not the major factor driving PEG-NP - macrophage interactions. First, mouse and human blood proteins had insignificant affinity for PEG-NPs. Second, PEG-NPs bound macrophages in the absence of serum proteins. Third, lipoproteins blocked PEG-NP binding to macrophages. Because of these findings, we tested the postulate that PEG-NPs bind (apo)lipoprotein receptors. Indeed, PEG-NPs triggered an in vitro macrophage transcription program that was similar to that triggered by lipoproteins and different from that triggered by lipopolysaccharide (LPS) and group A Streptococcus. Unlike LPS and pathogens, PLs did not increase transcripts involved in phagocytosis or inflammation. High-density lipoprotein (HDL) and SNPs triggered remarkably similar mouse bone-marrow-derived macrophage transcription programs. Unlike opsonized pathogens, CNPs, SNPs, and PLs lowered macrophage autophagosome levels and either reduced or did not increase the secretion of key macrophage pro-inflammatory cytokines and chemokines. Thus, the sequential opsonization and phagocytosis process is likely a minor aspect of PEG-NP - macrophage interactions. Instead, PEG-NP interactions with (apo)lipoprotein and scavenger receptors appear to be a strong driving force for PEG-NP - macrophage binding, entry, and downstream effects. We hypothesize that the high presence of these receptors on liver macrophages and on liver sinusoidal endothelial cells is the reason PEG-NPs localize rapidly and strongly to the liver.

Interactions of Apolipoproteins with Lipid-Based Nanoparticles.

Serum proteins bind and form a dynamic protein corona around nanoparticles (NPs) that have been injected into the mammalian vasculature. Several fundamental studies have shown that apolipoproteins are prominent components of the NP corona. Since apolipoproteins control the distribution of lipoproteins, they may also control the distribution of NPs. Indeed, apolipoprotein affinity for NPs has been recently taken advantage of to deliver CRISPR reagents encapsulated in NPs to cells that express particular lipoprotein receptors. In this scenario, an apolipoprotein binds an NP and the resulting apolipoprotein-NP complex binds a cell that expresses the (apo)lipoprotein receptor. But the NP will be diverted from the target cell if it does not express the (apo)lipoprotein receptor. This may hamper NP treatment of diseases. Therefore, we must understand the kinetics of apolipoprotein-NP affinity and how apolipoprotein-NP interactions affect NP biodistribution. In this Perspective, we discuss the evolving topic of apolipoprotein-NP interactions, which is of great interest for all NP-based disease treatments. Many properties of apolipoprotein-NP complexes are yet to be determined and will have a significant impact on NP efficacy for many NP-based treatments in animal models and in the clinic.

Multistability and circuit implementation of tabu learning two-neuron model: application to secure biomedical images in IoMT.

In this paper, the dynamics of a non-autonomous tabu learning two-neuron model is investigated. The model is obtained by building a tabu learning two-neuron (TLTN) model with a composite hyperbolic tangent function consisting of three hyperbolic tangent functions with different offsets. The possibility to adjust the compound activation function is exploited to report the sensitivity of non-trivial equilibrium points with respect to the parameters. Analysis tools like bifurcation diagram, Lyapunov exponents, phase portraits, and basin of attraction are used to explore various windows in which the neuron model under the consideration displays the uncovered phenomenon of the coexistence of up to six disconnected stable states for the same set of system parameters in a TLTN. In addition to the multistability, nonlinear phenomena such as period-doubling bifurcation, hysteretic dynamics, and parallel bifurcation branches are found when the control parameter is tuned. The analog circuit is built in PSPICE environment, and simulations are performed to validate the obtained results as well as the correctness of the numerical methods. Finally, an encryption/decryption algorithm is designed based on a modified Julia set and confusion-diffusion operations with the sequences of the proposed TLTN model. The security performances of the built cryptosystem are analyzed in terms of computational time (CT = 1.82), encryption throughput (ET = 151.82 MBps), number of cycles (NC = 15.80), NPCR = 99.6256, UACI = 33.6512, χ 2-values = 243.7786, global entropy = 7.9992, and local entropy = 7.9083. Note that the presented values are the optimal results. These results demonstrate that the algorithm is highly secured compared to some fastest neuron chaos-based cryptosystems and is suitable for a sensitive field like IoMT security.

Window of multistability and its control in a simple 3D Hopfield neural network: application to biomedical image encryption.

In this contribution, the problem of multistability control in a simple model of 3D HNNs as well as its application to biomedical image encryption is addressed. The space magnetization is justified by the coexistence of up to six disconnected attractors including both chaotic and periodic. The linear augmentation method is successfully applied to control the multistable HNNs into a monostable network. The control of the coexisting four attractors including a pair of chaotic attractors and a pair of periodic attractors is made through three crises that enable the chaotic attractors to be metamorphosed in a monostable periodic attractor. Also, the control of six coexisting attractors (with two pairs of chaotic attractors and a pair of periodic one) is made through five crises enabling all the chaotic attractors to be metamorphosed in a monostable periodic attractor. Note that this controlled HNN is obtained for higher values of the coupling strength. These interesting results are obtained using nonlinear analysis tools such as the phase portraits, bifurcations diagrams, graph of maximum Lyapunov exponent, and basins of attraction. The obtained results have been perfectly supported using the PSPICE simulation environment. Finally, a simple encryption scheme is designed jointly using the sequences of the proposed HNNs and the sequences of real/imaginary values of the Julia fractals set. The obtained cryptosystem is validated using some well-known metrics. The proposed method achieved entropy of 7.9992, NPCR of 99.6299, and encryption time of 0.21 for the 256*256 sample 1 image.

Australian pharmacists' perspectives on physician-assisted suicide (PAS): thematic analysis of semistructured interviews.

OBJECTIVES: This study aimed to investigate Australian pharmacists' views about their role in physician-assisted suicide (PAS), their ethical and legal concerns and overall thoughts about PAS in pharmacy. DESIGN: Semistructured interviews of pharmacists incorporating a previously validated vignette and thematic analysis. SETTING: Australia (face to face or phone call). PARTICIPANTS: 40 Australian Health Practitioner Regulation Agency registered pharmacists, majority women (65%) with varied experiences in community, hospital, industry, academia, government and other fields. RESULTS: Emergent themes from the interviews were: legal and logistical framework, ethical framework, training and guidance and healthcare budget. More than half the participants supported the role of pharmacists in the supply of medicines for PAS, while less than half were either against or unsure of the legislation of PAS in Australia. Shared concerns included transparency of prescribing practices and identification of authorised physicians involved in PAS, which were consistent with existing literature. Religious faith, emotion and professional autonomy were key indicators for the implementation of conscientious objection to the supply of medicines in PAS. Re-evaluation of current guidelines, pharmacist training and government reimbursement was also of significance from participants' perspectives. CONCLUSION: This study revealed current concerns of practising pharmacists in Australia, including previously undocumented perspectives on the pharmacoeconomic impact of and barriers relating to PAS. The need for training of all healthcare professionals involved, the provision of clear guidelines, including regulation around storage, administration and disposal of medicines dispensed for PAS and the updating of current therapeutic guidelines around end-of-life care were all issues delineated by this study. These findings highlighted the need for current and future policies to account for all stakeholders involved in PAS, not solely prescribers.

The Role of Medicinal Cannabis in Clinical Therapy: Pharmacists' Perspectives.

BACKGROUND: Medicinal cannabis has recently attracted much media attention in Australia and across the world. With the exception of a few countries, cannabinoids remain illegal-known for their adverse effects rather than their medicinal application and therapeutic benefit. However, there is mounting evidence demonstrating the therapeutic benefits of cannabis in alleviating neuropathic pain, improving multiple sclerosis spasticity, reducing chemotherapy induced nausea and vomiting, and many other chronic conditions. Many are calling for the legalisation of medicinal cannabis including consumers, physicians and politicians. Pharmacists are the gatekeepers of medicines and future administrators/dispensers of cannabis to the public, however very little has been heard about pharmacists' perspectives. Therefore the aim of this study was to explore pharmacists' views about medicinal cannabis; its legalisation and supply in pharmacy. METHODS: Semi-structured interviews with 34 registered pharmacists in Australia were conducted. All interviews were audio-recorded, transcribed ad verbatim and thematically analysed using the NVivo software. RESULTS: Emergent themes included stigma, legislation, safety and collaboration. Overall the majority of pharmacists felt national legalisation of a standardised form of cannabis would be suitable, and indicated various factors and strategies to manage its supply. The majority of participants felt that the most suitable setting would be via a community pharmacy setting due to the importance of accessibility for patients. DISCUSSION: This study explored views of practicing pharmacists, revealing a number of previously undocumented views and barriers about medicinal cannabis from a supply perspective. There were several ethical and professional issues raised for consideration. These findings highlight the important role that pharmacists hold in the supply of medicinal cannabis. Additionally, this study identified important factors, which will help shape future policies for the successful implementation of medicinal cannabis in healthcare. We recommend that these views and strategies be incorporated in the development of policies and legislations.