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Multiple sclerosis (MS) is a debilitating disease that requires prolonged treatment with often severe side effects. One experimental MS therapeutic currently under development is a single amino acid mutant of a plant peptide termed kalata B1, of the cyclotide family. Like all cyclotides, the therapeutic candidate [T20K]kB1 is highly stable as it contains a cyclic backbone that is cross-linked by three disulfide bonds in a knot-like structure. This stability is much sought after for peptide drugs, which despite exquisite selectivity for their targets, are prone to rapid degradation in human serum. In preliminary investigations, it was found that [T20K]kB1 retains oral activity in experimental autoimmune encephalomyelitis, a model of MS in mice, thus opening up opportunities for oral dosing of the peptide. Although [T20K]kB1 can be synthetically produced, a recombinant production system provides advantages, specifically for reduced scale-up costs and reductions in chemical waste. In this study, we demonstrate the capacity of the Australian native Nicotiana benthamiana plant to produce a structurally identical [T20K]kB1 to that of the synthetic peptide. By optimizing the co-expressed cyclizing enzyme, precursor peptide arrangements, and transgene regulatory regions, we demonstrate a [T20K]kB1 yield in crude peptide extracts of ~ 0.3 mg/g dry mass) in whole plants and close to 1.0 mg/g dry mass in isolated infiltrated leaves. With large-scale plant production facilities coming on-line across the world, the sustainable and cost-effective production of cyclotide-based therapeutics is now within reach., (© 2023. The Author(s).)

Purpose: Prostate-specific membrane antigen (PSMA) PET/CT is increasingly used in patients with biochemical recurrence post prostatectomy to detect local recurrence and metastatic disease at low PSA levels. The aim of this study was to assess patterns of disease detection, predictive factors and safety using [ 18 F]DCFPyL PET/CT versus diagnostic CT in patients being considered for salvage radiotherapy with biochemical recurrence post prostatectomy., Methods: We conducted a prospective trial recruiting 100 patients with detectable PSA post prostatectomy (PSA 0.2-2.0 ng/mL) and referred for salvage radiotherapy from August 2018 to July 2020. All patients underwent a PSMA PET/CT using the [ 18 F]DCFPyL tracer and a diagnostic CT. The detection rates of [ 18 F]DCFPyL PET/CT vs diagnostic CT were compared and patterns of disease are reported. Clinical patient and tumour characteristics were analysed for predictive utility. Thirty-day post-scan safety is reported., Results: Of 100 patients recruited, 98 were suitable for analysis with a median PSA of 0.32 ng/mL. [ 18 F]DCFPyL PET/CT was positive 46.4% and equivocal 5.2%, compared to 15.5% positivity for diagnostic CT. Local recurrence was detected on [ 18 F]DCFPyL PET/CT in 28.5%, nodal disease in 27.5% and bony metastases in 6.1% of patients. Both ISUP grade group (p < 0.001) and pre-scan PSA (p = 0.029) were significant predictors of [ 18 F]DCFPyL PET/CT positivity, and logistic regression generated probabilities combining the two showed improved prediction rates. No significant safety events were reported post [ 18 F]DCFPyL administration., Conclusions: [ 18 F]DCFPyL PET/CT increases detection of disease in patients with biochemical recurrence post prostatectomy compared to diagnostic CT. Patients being considered for salvage radiotherapy with a PSA >0.2 ng/mL should be considered for [ 18 F]DCFPyL PET/CT scan., Trial Registration: Australian New Zealand Clinical Trials Registry Number: ACTRN12618001530213 ( http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375932&isReview=true )., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To explore the effectiveness of the enuresis alarm with overlearning for treatment of primary nocturnal enuresis (PNE). A key objective was to explore the effect of overlearning on treatment gains, and its impact on relapse., Patients and Methods: The RMIT University Psychology Clinic has been treating PNE in the community for more than 20 years following a standardized treatment protocol. The study analysed archival data of 126 participants, aged ≥ 5 years, presenting with PNE. A mean wetting frequency of 5.13 wet nights per week was observed at baseline., Results: Treatment significantly reduced mean wetting from baseline levels during both treatment and overlearning phases, F(1.41, 176.10) = 588.54, p < 0.001, r(2) = 0.77, 95% CI (0.74-0.81). Wet nights per week reduced from a mean of 5.13 (SD = 1.77) during baseline to 1.88 (SD = 0.85) during treatment, and 0.64 (SD = 0.60) during overlearning. Alarm treatment with overlearning produced a treatment response of 87%, compared with 59% for alarm treatment only., Conclusions: Evidence of improved treatment response with the addition of overlearning suggests overlearning should be considered as a potentially useful adjunct to alarm treatment for PNE. Overlearning was not unreasonably onerous for participants. Further research is required to explore the impact overlearning has on reducing relapse rates., (Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)