PURPOSE In this study, we aimed to improve our knowledge of insular epilepsy by studying anatomoelectroclinical correlations in pure insular-onset epilepsy and characterizing differences between anterior and posterior insular-onset seizures. METHODS Patients in whom seizure-onset zone was confined to the insula and peri-insular sulcus were selected from 301 consecutive presurgical stereo-electroencephalography (EEG) recordings performed between years 2010 and 2017 in two epilepsy centers. Ictal-onset zone in stereo-EEG was delineated visually and quantitatively using epileptogenic index method. Seizure characteristics were reanalyzed, and anatomoelectroclinical correlations were assessed. Characteristics of posterior and anterior insular-onset seizures were compared. RESULTS Eleven insular cases were identified, five of them with an anterior insular seizure onset and six with a posterior one. Nonpainful somatosensory symptoms and autonomic symptoms were the most common symptoms (73% of patients) followed by speech-related symptoms (55%) and ipsilateral eye blinking (45%). Six patients had seizures restricted to somatosensory or viscerosensory symptoms. In all patients, seizures progressed to motor symptoms. Somatosensory symptoms did not differentiate anterior from posterior insular seizures. However, hyperkinetic signs, speech modifications, and viscerosensory symptoms were related to an anterior insular seizure-onset zone. Pain, asymmetric tonic, focal clonic, and tonic symptoms were more frequent in patients with a posterior insular seizure onset. CONCLUSIONS Seizure semiology is heterogeneous in pure insular-onset epilepsy. Differences between the anterior and posterior insular seizures reflect the functional organization of the insula. Particularly, the different types of motor symptoms may help to distinguish anterior from posterior insular seizure onset. OBJECTIVES This study aimed to investigate the prevalence of psychogenic nonepileptic seizures (PNES) and PNES-epilepsy coexistence within all video-electroencephalography (EEG) monitoring unit (VEMU) referrals and to identify semiological and electrophysiological features to differentiate patients with PNES-epilepsy coexistence from PNES-only. METHODS We retrospectively reviewed medical files, VEMU reports, and videos of 1983 adult patients. Demographical, historical, clinical, neuroimaging, and electrophysiological parameters of all patients were recorded. We classified patients into five groups as definite PNES-only, definite PNES-epilepsy coexistence, definite PNES-probable epilepsy coexistence, probable PNES-definite epilepsy coexistence, and probable PNES-only. We defined a "definite" group when we saw the ictal EEG and/or video recording of the seizure. The "probable" term is used when there is strong evidence from the history of a particular seizure type and suggestive interictal EEGs without video reonly. Medicine shortages have been spreading in European countries. selleck products In many cases, the unavailability of medicinal products has a substantial impact on the capability of National Healthcare Systems in ensuring the continuity of care. Shortages originate from multifactorial causes. In particular, they can be due to supply-related factors (e.g., manufacturing issues, regulatory issues, logistics, distribution) and demand-related ones (e.g., fluctuating drug demand, parallel market, tendering, price and reimbursement policies). However, some extraordinary geopolitical events (e.g., Brexit) may also affect medicines' availability. The capability of European Regulatory Authorities and other stakeholders, which are involved in the pharmaceutical distribution chain and the healthcare assistance services, to define suitable problem-solving strategies has been limited for years by the fragmentation of the European regulatory framework, starting from the lack of a univocal definition of a medicine shortage. Only in 2019, the EMA and HMA joint task force released the first harmonized "shortage" definition in the European Economic Area (EEA) and guidance on public communication. This manuscript aims to review the current European regulatory framework on medicine shortages. To support the activities of regulators, manufacturers and other healthcare professionals, an algorithm was also proposed to be used as a harmonized procedure to determine the shortage/unavailability impact on public health and to rationalize the problem-solving strategies adopted in all different settings. When reinforcer availability on one alternative of a concurrent schedule is signaled by a discriminative stimulus, responding on that alternative decreases. We investigated how the correlation between signal presentation and reinforcement (signal reliability) affects choice between signaled and unsignaled alternatives. Six pigeons responded in a concurrent schedule, in which reinforcers on one alternative were signaled by a key-color change. Across conditions, the probability of reinforcement following signal presentation varied (the probability in its absence was the complement). As signal reliability increased, response rates and latencies following signal onset on the signaled alternative decreased, whereas responding on the unsignaled alternative remained unchanged. Because the signal did not alter overall reinforcer rates, these findings are consistent with matching theories and research suggesting that responding on one alternative of a concurrent schedule depends on reinforcer, but not response, rates on other alternatives. However, these findings are inconsistent with others demonstrating concomitant changes in responding on signaled and unsignaled alternatives. We consider whether a response-competition account of concurrent performance can explain these discrepancies, and suggest avenues for future studies to investigate the mechanisms underlying effects of signaled reinforcement in concurrent schedules. Dietary and microbial indoles can act as ligands and activators of pregnane X receptor (PXR), with implications in human intestinal health. In the current study, we examined the effects of simple mono-methylated indoles (MMIs) on the activity and function of PXR, using a series of human hepatic and intestinal cell models. Indoles 1-MMI and 2-MMI strongly induced CYP3A4 and MDR1 mRNAs in human intestinal adenocarcinoma cells LS180, but not in primary human hepatocytes. The levels of CYP3A4 mRNA were increased by 1-MMI and 2-MMI in wild type, but not in PXR-knock-out human hepatic progenitor HepaRG cells, implying the involvement of PXR in CYP3A4 induction by MMIs. Utilizing reporter gene assay, we observed dose-dependent activation of PXR by all MMIs, and their efficacies and potencies were comparable. Tested MMIs also displayed moderate antagonist effects on PXR, revealing about partial agonist effects of these compounds. As demonstrated using the Chromatin immunoprecipitation assay (ChIP),1-MMI increased PXR occupancy of the CYP3A4 promoter.