Targeted quantitation of 48 basic taste-active compounds in commercial meatlike process flavors, calculation of dose-overthreshold factors, and basic taste re-engineering, followed by activity-guided fractionation, revealed, next to l-glutamate and 5′-ribonucleotides, a series of N-acetylated amino acids and S-((4-amino-2-methylpyrimidin-5-yl)­methyl)-l-cysteine as taste-modulating compounds. The N-acetylated amino acids imparted kokumi enhancement with rather high taste thresholds ranging up to 1800 μmol/L (N-acetylmethionine) in model broth. In comparison, S-((4-amino-2-methylpyrimidin-5-yl)­methyl)-l-cysteine, found to be formed by a Maillard-type reaction of thiamine and cysteine, is reported for the first time to exhibit strong kokumi enhancement above a low threshold concentration of 120 μmol/L (model broth). These results will open new avenues toward a knowledge-based optimization of thiamine-containing process flavors.

Increasing the thiamine concentration in a respective process flavor yields a product with a significant higher kokumi activity. S-plot analysis of the mass spectrometric data revealed beside thiamine itself, 4-methyl-5-thiazoleethanol, (S)-((4-amino-2-methylpyrimidin-5-yl)­methyl)-l-cysteine, N-((4-amino-2-methylpyrimidin-5-yl)­methyl)­formamide, 3-(((4-amino-2-methylpyrimidin-5-yl)­methyl)­thio)-5-hydroxypentan-2-one, and 2-methyl-5-(((2-methylfuran-3-yl)­thio)­methyl)­pyrimidin-4-amine as marker molecules for a process flavor with higher thiamine concentration. Sensory-based targeted isolation revealed that (S)-((4-amino-2-methylpyrimidin-5-yl)­methyl)-l-cysteine, 3-(((4-amino-2-methylpyrimidin-5-yl)­methyl)­thio)-5-hydroxypentan-2-one, and 2-methyl-5-(((2-methylfuran-3-yl)­thio)­methyl)­pyrimidin-4-amine showed an influence on the kokumi taste activity with taste threshold concentrations between 35 and 120 μmol/L. An adapted mass spectrometric-based carbon module labeling experiment as well as quantitative studies clearly demonstrated thiamine as the only precursor and an intermolecular formation pathway for the compounds (S)-(((4-amino-2-methylpyrimidin-5-yl)­methyl)­thio)-5-hydroxypentan-2-one and 2-methyl-5-(((2-methylfuran-3-yl)­thio)­methyl)­pyrimidin-4-amine. On the basis of the knowledge that several thiamine derivatives showed taste-modulating activity, selected thiamine-based binary model reactions and synthesis were carried out. This resulted in the isolation of further thiamine-derived taste modulators like (S)-((4-amino-2-methylpyrimidin-5-yl)­methyl)-l-cysteinylglycine, (S)-3-((((4-amino-2-methylpyrimidin-5-yl)­methyl)­thio)­methyl)­piperazine-2,5-dione, 3-(((4-amino-2-methylpyrimidin-5-yl)­methyl)­thio)­pentan-2-one, 5-(((furan-2-ylmethyl)­thio)­methyl)-2-methylpyrimidin-4-amine, and (4-amino-2-methylpyrimidin-5-yl)­methanethiol, 2-methyl-5-((methylthio)­methyl)­pyrimidin-4-amine with taste thresholds ranging from 35 to 880 μmol/L.

The objective of this paper is to address ethical and training considerations with behavioral health (BH) services practicing within rural, integrated primary care (IPC) sites through the conceptual framework of an ethical acculturation model. Method: Relevant articles are presented along with a description of how the acculturation model can be implemented to address ethical dilemmas. Results: Recommendations are provided regarding practice considerations when using the acculturation model and the utility of the model for both established BH practitioners and trainees. Conclusions: Psychologists integrated into rural IPC teams may be able to enhance their ethical practice and improve outcomes for patients and families through the use of the acculturation model. Psychologists serving as supervisors can utilize the acculturation model to provide valuable experiences to trainees in addressing ethical dilemmas when competing ethical principles are present. Implications for Impact StatementBy addressing ethical dilemmas through an acculturation model, psychologists may prevent themselves from drifting away from American Psychological Association ethical principles within the context of a multidisciplinary team while simultaneously providing valuable learning opportunities for trainees. This focus is particularly important in rural settings where access to specialty care and other resources are limited, and a psychologist may be the only licensed behavioral health provider on a multidisciplinary team.

Although domesticated potatoes contain a large variety of steroidal glycoalkaloids (SGAs) and saponins, in the past, many research projects mainly focused on the two major SGAs, α-solanine and α-chaconine. This study investigates the quantitative changes, induced by post-harvest LED light exposure, of six SGAs and four saponins in 12 potato cultivars at three different time points (1, 7, and 16 days), by using ultra-performance liquid chromatography tandem mass spectrometry. Altogether, SGA contents of 3.0−17.1 mg/100 g fresh weight (FW) could be observed in the analyzed tubers with potato varieties highly exceeding the newly discussed safety limit of 10 mg/100 g. The overall contents of 0.1−5.4 mg/100 g FW of the so far barely studied saponins, like protoneodioscin or barogenin-solatrioside, highly differed between the assayed potato cultivars. Furthermore, cultivar-specific regulations of SGAs and saponins could be observed due to light exposure.

<b><i>Introduction:</i></b> A phase I, open-label clinical trial in healthy male subjects was conducted to assess the pharmacokinetic and safety profile of an oromucosal cannabinoid spray (AP701) containing a lipid-based nanoparticular drug formulation standardized to ∆-9-tetrahydrocannabinol (THC). <b><i>Methods:</i></b> Twelve healthy male subjects received a single dose of AP701 (12 sprays) containing 3.96 mg THC. Plasma samples were drawn 10 min–30 h post dose for analysis of THC and the active metabolite 11-hydroxy-∆-9-THC (11-OH-THC). <b><i>Results:</i></b> The single dose of the applied oromucosal cannabinoid spray AP701 (12 sprays, 3.96 mg THC) resulted in a mean maximum plasma concentration (<i>C</i>_max) of 2.23 ng/mL (90% CI 1.22–3.24) and a mean overall exposure (area under the concentration-time curve from time 0 to last measurable concentration [AUC_0–t]) of 7.74 h × ng/mL (90% CI 5.03–10.45) for THC. For the active metabolite 11-OH-THC, a <i>C</i>_max of 2.09 mg/mL (90% CI 1.50–2.68) and AUC_0–t of 10.4 h × ng/mL (90% CI 7.03–13.77) was found. The oromucosal cannabinoid spray AP701 caused only minor psychotropic effects despite the relatively high dosage applied by healthy subjects. No serious adverse effects occurred. Overall, the oromucosal cannabinoid spray AP701 was well tolerated. <b><i>Conclusion:</i></b> Compared to currently available drugs on the market, higher AUC values could be detected for the oromucosal cannabinoid spray AP701 despite administration of a lower dose. These comparatively higher blood levels caused only minor psychotropic adverse effects. The oromucosal cannabinoid spray AP701 was well tolerated at a single dose of 3.96 mg THC. The oromucosal administration may provide an easily applicable and titratable drug formulation with a high safety and tolerability profile.