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Background: Chat Generative Pre-trained Transformer (ChatGPT) is a language model that may have the potential to revolutionize health care. The study purpose was to test whether ChatGPT could be used to create educational brochures about kidney transplant tailored for three target audiences: caregivers, teens and children., Methods: Using a list of 25 educational topics, standardized prompts were employed to ensure content consistency in ChatGPT generation. An expert panel assessed the accuracy of the content by rating agreement on a Likert scale (1 = <25 % agreement; and 5 = 100 % agreement). The understandability, actionability and readability of the brochures were assessed using the Patient Education Materials Assessment Tool for printable materials (PEMAT-P) and standard readability scales. A caregiver and patient reviewed and provided written feedback., Results: We found mean understandability scores of 69 %, 66 %, and 73 % for caregiver, teen, and child brochures respectively, with 90.7 % of the ChatGPT generated brochures scoring 40 % on the actionability scale. Generated caregiver and teen materials achieved readability levels of grades 9-14, while child-specific brochures achieved readability levels of grades 6-11. Brochures were formatted appropriately but lacked depth., Conclusion: ChatGPT demonstrates potential for rapidly generating patient education materials; however, challenges remain in ensuring content specificity. We share the lessons learned to assist other healthcare providers with using this technology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Prion diseases are rare and obligatory fatal neurodegenerative disorders caused by the accumulation of a misfolded isoform (PrPSc) of the host-encoded prion protein (PrPc). Prophylactic and therapeutic regimens against prion diseases are very limited. To extend such strategies we selected peptide aptamers binding to PrP from a combinatorial peptide library presented on the Escherichia coli thioredoxin A (trxA) protein as a scaffold. In a yeast two-hybrid screen employing full-length murine PrP (aa 23-231) as a bait we identified three peptide aptamers that reproducibly bind to PrP. Treatment of prion-infected cells with recombinantly expressed aptamers added to the culture medium abolished PrPSc conversion with an IC50 between 350 and 700 nM. For expression in eukaryotic cells, peptide aptamers were fused to an N-terminal signal peptide for entry of the secretory pathway. The C terminus was modified by a glycosyl-phosphatidyl-inositol-(GPI) anchoring signal, a KDEL retention motif and the transmembrane and cytosolic domain of LAMP-I, respectively. These peptide aptamers retained their binding properties to PrPc and, depending on peptide sequence and C-terminal modification, interfered with endogenous PrPSc conversion upon expression in prion-infected cells. Notably, infection of cell cultures could be prevented by expression of KDEL peptide aptamers. For the first time, we show that trxA-based peptide aptamers can be targeted to the secretory pathway, thereby not losing the affinity for their target protein. Beside their inhibitory effect on prion conversion, these molecules could be used as fundament for rational drug design.

Background: Cardiac beta receptor down-regulation is associated with a reduction of tissue cyclic adenosine monophosphate (AMP) content. Milrinone exerts its effects by inhibiting the metabolism of existing cyclic AMP. The purpose of this study was to evaluate the effect of reduced myocardial cyclic AMP content on the pharmacologic action of milrinone., Methods: A reduction of myocardial cyclic AMP content was produced by creating catecholamine depletion in the hearts of adult guinea pigs with intraperitoneal reserpine. Control animals received the reserpine vehicle. Isolated heart perfusion was maintained with modified Krebs buffer, and hearts were paced at 270 beats/min. A latex balloon and transducer-tipped catheter were inserted into the left ventricle. Isovolemic work was maintained at a constant balloon volume. Hearts from control and reserpine treated animals were perfused for 20 minutes with buffer containing either no milrinone, 1.7 x 10(-6), or 1.0 x 10(-4) mol/L milrinone (n = 12 for each dose). Maximal positive and negative dP/dt were assessed. The hearts were then frozen and cyclic AMP was measured., Results: Cyclic AMP content was significantly lower in the reserpine-treated hearts at each milrinone concentration (0.33 +/- 0.01 vs 0.46 +/- 0.01; 0.33 +/- 0.01 vs 0.53 +/- 0.01; 0.30 +/- 0.01 vs 0.61 +/- 0.02 pmol/mg wet weight, p < 0.05). Milrinone significantly increased positive and negative dP/dtmax (p < 0.05), but no difference was observed between control and reserpine-treated hearts., Conclusions: Endogenous catecholamine depletion reduces myocardial cyclic AMP content but does not attenuate the response to milrinone in the isolated heart.