In vitro cellular uptake and neuroprotective efficacy of poly-arginine-18 (R18) and poly-ornithine-18 (O18) peptides: critical role of arginine guanidinium head groups for neuroprotection.

We have previously demonstrated that Cationic Arginine-Rich Peptides (CARPs) and in particular poly-arginine-18 (R18; 18-mer of arginine) exhibit potent neuroprotective properties in both in vitro and in vivo neuronal injury models. Based on the current literature, there is a consensus that arginine residues by virtue of their positive charge and guanidinium head group is the critical element for imparting CARP neuroprotective properties and their ability to traverse cell membranes. This study examined the importance of guanidinium head groups in R18 for peptide cellular uptake, localization, and neuroprotection. This was achieved by using poly-ornithine-18 (O18; 18-mer of ornithine) as a control, which is structurally identical to R18, but possesses amino head groups rather than guanidino head groups. Epifluorescence and confocal fluorescence microscopy was used to examine the cellular uptake and localization of the FITC-conjugated R18 and O18 in primary rat cortical neurons and SH-SY5Y human neuroblastoma cell cultures. An in vitro cortical neuronal glutamic acid excitotoxicity model was used to compare the effectiveness of R18 and O18 to inhibit cell death and intracellular calcium influx, as well as caspase and calpain activation. Fluorescence imaging studies revealed cellular uptake of both FITC-R18 and FITC-O18 in neuronal and SH-SY5Y cells; however, intracellular localization of the peptides differed in neurons. Following glutamic acid excitotoxicity, only R18 was neuroprotective, prevented caspases and calpain activation, and was more effective at reducing neuronal intracellular calcium influx. Overall, this study demonstrated that for long chain cationic poly-arginine peptides, the guanidinium head groups provided by arginine residues are an essential requirement for neuroprotection but are not required for entry into neurons.

Health consumers' ethical concerns towards artificial intelligence in Australian emergency departments.

OBJECTIVES: To investigate health consumers' ethical concerns towards the use of artificial intelligence (AI) in EDs. METHODS: Qualitative semi-structured interviews with health consumers, recruited via health consumer networks and community groups, interviews conducted between January and August 2022. RESULTS: We interviewed 28 health consumers about their perceptions towards the ethical use of AI in EDs. The results discussed in this paper highlight the challenges and barriers for the effective and ethical implementation of AI from the perspective of Australian health consumers. Most health consumers are more likely to support AI health tools in EDs if they continue to be involved in the decision-making process. There is considerably more approval of AI tools that support clinical decision-making, as opposed to replacing it. There is mixed sentiment about the acceptability of AI tools influencing clinical decision-making and judgement. Health consumers are mostly supportive of the use of their data to train and develop AI tools but are concerned with who has access. Addressing bias and discrimination in AI is an important consideration for some health consumers. Robust regulation and governance are critical for health consumers to trust and accept the use of AI. CONCLUSION: Health consumers view AI as an emerging technology that they want to see comprehensively regulated to ensure it functions safely and securely with EDs. Without considerations made for the ethical design, implementation and use of AI technologies, health consumer trust and acceptance in the use of these tools will be limited.