lic-assisted therapies and could, in the long-term, open new treatment avenues in several domains. Forthcoming studies shouldassess toxicity/safety and clinical outcomes of patients receiving Amazonian tobacco-based treatment.To our knowledge, this is the first study employing a transdisciplinary clinical approach to examine therapeutic applications of tobacco by an Amazonian tabaquero. Our findings significantly contribute to the growing research literature on Amazonian medicine and emergent psychedelic-assisted therapies and could, in the long-term, open new treatment avenues in several domains. Forthcoming studies should assess toxicity/safety and clinical outcomes of patients receiving Amazonian tobacco-based treatment.A series of trifluoromethylated pyrazole thiosemicarbazone, trifluromethylated pyrazole isothiosemicarbazone, and trifluoromethylated pyrazole 2-amino-1,3,4-thiadiazole hybrids were synthesized and evaluated in vitro against the promastigote form of Leishmania amazonensis and the epimastigote form of Trypanosoma cruzi, the pathogens causing the neglected tropical diseases leishmaniasis and Chagas disease, respectively. The results show the potential of these compounds regarding their antiparasitic properties. Studies on the structure-activity relationship demonstrated that compounds containing a bulky group at the para position of the phenyl ring attached to the 5-position of the pyrazole core had better antiparasitic effects. Among the substituents attached at the 3-position of the pyrazole ring, the insertion of the 2-amino-1,3,4-thiadiazole nucleus led to the most potent compounds compared to the thiosemicarbazone derivative.Cannabis extracts in oil are becoming increasingly available, and, during the last years, there has been growing public and scientific interest about therapeutic properties of these compounds for the treatment of several neurologic diseases, not just epilepsy. The discovered role of the endocannabinoid system in epileptogenesis has provided the basis to investigate the pharmacological use of exogenously produced cannabinoids, to treat epilepsy. Although, physicians show reluctance to recommend Cannabis extracts given the lack of high-quality safety available data, from literature data cannabidiol (CBD) results to be a promising and safe anticonvulsant drug with low side-effect. In particular, according to early studies, CBD can reduce the frequency of seizures and lead to improvements in quality of life in children affected by refractory epilepsy. So, for these reasons, the detailed study of the interactions between CBD and anticonvulsant drugs (AEDs) administered simultaneously in polytherapy, is arousing increasing interest, to clarify and to assess the incidence of adverse effects and the relation between dose escalation and quality of life measures. To date, in pediatric age, CBD efficacy and safety is not supported by well-designed trials and strong scientific evidence are not available. These studies are either retrospective or small-scale observational and only during the last years Class I evidence data for a pure form of CBD have been available, as demonstrated in placebo-controlled RCTs for patients affected by Lennox-Gastaut syndrome and Dravet syndrome. It is necessary to investigate CBD safety, pharmacokinetics and interaction with other AEDs alongside performing double-blinded placebo-controlled trials to obtain conclusive data on its efficacy and safety in the most frequent epilepsies in children, not just in the epileptic encephalopathy. This review was aimed to revise the available data to describe the scientific evidence for CBD in Pediatric Epilepsies.Transdermal drug delivery is a key technology for administering drugs. However, most devices are "one-size-fits-all", even though drug diffusion through the skin varies significantly from person-to-person. For next-generation devices, personalization for optimal drug release would benefit from an augmented insight into the drug release and percutaneous uptake kinetics. Kaempferide Our objective was to quantify the changes in transdermal fentanyl uptake with regards to the patient's age and the anatomical location where the patch was placed. We also explored to which extent the drug flux from the patch could be altered by miniaturizing the contact surface area of the patch reservoir with the skin. To this end, we used validated mechanistic modeling of fentanyl diffusion, storage, and partitioning in the epidermis to quantify drug release from the patch and the uptake within the skin. A superior spatiotemporal resolution compared to experimental methods enabled in-silico identification of peak concentrations and fluxes, anof drug delivery systems. Here, the validated mechanistic models can serve as a key building block for developing digital twins for transdermal drug delivery systems.Pregnancy may induce the onset or exacerbation of autoimmune bullous diseases such as pemphigus or pemphigoid gestationis. A shift toward T helper (Th) 2 immune response and the influence of hormonal changes have been evoked as possible triggering factors. Therapeutic management of this setting of patients may represent a challenge, mainly due to safety concerns of some immunosuppressive drugs during pregnancy and lactation. In this narrative review, we provided a comprehensive overview of the therapeutic management of autoimmune bullous diseases in pregnant and breastfeeding women, focusing on pemphigus and pemphigoid gestationis.In recent years, transmembrane voltage has been found to modify agonist potencies at several G protein-coupled receptors (GPCRs). Whereas the voltage sensitivities of the Gαi/o-coupled dopamine D2-like receptors (D2R, D3R, D4R) have previously been investigated, the putative impact of transmembrane voltage on agonist potency at the mainly Gαs/olf-coupled dopamine D1-like receptors (D1R, D5R) has hitherto not been reported. Here, we assayed the potency of dopamine in activating G protein-coupled inward rectifier potassium (GIRK) channels co-expressed with D1R and D5R in Xenopus oocytes, at -80 mV and at 0 mV. Furthermore, GIRK response deactivation rates upon dopamine washout were measured to estimate dopamine dissociation rate (koff) constants. Depolarization from -80 to 0 mV was found to reduce dopamine potency by about 7-fold at both D1R and D5R. This potency reduction was accompanied by an increase in estimated dopamine koffs at both receptors. While the GIRK response elicited via D1R was insensitive to pertussis toxin (PTX), the response evoked via D5R was reduced by 64% (-80 mV) and 71% (0 mV) in the presence of PTX.