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Béla Kiss, Zsolt Némethy, Károly Fazekas, Dalma Kurkó, István Gyertyán, Katalin Sághy, István Laszlovszky, Bence Farkas, Norbert Kirschner, Etelka Bolf-Terjéki, Ottilia Balázs, Balázs Lendvai Pharmacological and Drug Safety Research, Gedeon Richter Plc, Budapest, HungaryCorrespondence: Béla KissPharmacological and Drug Safety Research, Gedeon Richter Plc, P.O. Box 27, Budapest H-1475, HungaryTel +361 431 4226Fax +361 889 8400Email b.kiss@richter.huIntroduction: Cariprazine, a dopamine D3-preferring D3/D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist, has two major human metabolites, desmethyl-cariprazine (DCAR) and didesmethyl-cariprazine (DDCAR). The metabolite pharmacology was profiled to understand the contribution to cariprazine efficacy.Methods: In vitro receptor binding and functional assays, electrophysiology, animal models, microdialysis, and kinetic-metabolism approaches were used to characterize the pharmacology of DCAR and DDCAR. Results: Similar to cariprazine, both metabolites showed high affinity for human D3, D2L, 5-HT1A, 5-HT2A, and 5-HT2B receptors, albeit with higher selectivity than cariprazine for D3 versus D2 receptors. In [35S]GTPγS binding assays, cariprazine and DDCAR were antagonists in membranes from rat striatum and from cells expressing human D2 and D3 receptors, and were partial agonists in membranes from rat hippocampus. In cAMP signaling assays, cariprazine, DCAR, and DDCAR acted as partial agonists at D2 and D3 receptors; cariprazine and DDCAR were full agonists, whereas DCAR was a partial agonist at 5-HT1A receptors. Cariprazine, DCAR, and DDCAR were pure antagonists at human 5-HT2B receptors. Cariprazine and DDCAR increased rat striatal dopamine and reduced cortical serotonin turnover. Cariprazine and DDCAR showed similar in vivo D3 receptor occupancy in rat brain; however, cariprazine was more potent for D2 receptor occupancy. Both cariprazine and DDCAR dose-dependently but partially suppressed the spontaneous activity of midbrain dopaminergic neurons in rats, with the parent compound being more potent but shorter acting than its metabolite. Consistent with the D2 receptor occupancy profile, DDCAR was 3- to 10-fold less potent than cariprazine in rodent models of antipsychotic-like activity. Following acute cariprazine administration, DDCAR was detected in the rodent brain but at much lower levels than cariprazine.Conclusion: Overall, in vitro and in vivo pharmacological profiles of DCAR and DDCAR demonstrated high similarity with cariprazine, suggesting that the major metabolites of cariprazine contribute significantly to its clinical efficacy.Keywords: dopamine, serotonin, schizophrenia, bipolar disorder, desmethyl-cariprazine, didesmethyl-cariprazine

Introduction: Self-injurious behavior (SIB) among adolescents has become a hot topic in psychiatry. Despite the consensus that the prevalence of SIB is high, 26-22% among adolescence, there are conflicting results about whether it has increased in the 21st century and about the global distribution of the prevalence. Objectives: The aim of the current study was to make a systematic search and meta-analysis of publications from the last 5 years on the prevalence of SIB in adolescents and to examine definitions and assessments of SIB, gender, continental, and year differences. The hypotheses were the following: 1) the prevalence of SIB did not change over time between the examined period for both girls and boys; 2) girls reported a higher prevalence of a history of SIB than boys. Methods: The systematic search was made in June 2020. Six databases were used. The main search terms were "self-injurious behavior", "prevalence" and "adolescence". First the titles and abstracts of the relevant articles were checked, then the full texts were read and collected those papers that met the inclusion criteria. The inclusion criteria were the following: published between 01/01/2015, and 06/18/2020, focused on community sample, and written in English. Comprehensive Meta-Analysis software was used to conduct the analyses. Results: In sum, a total of 97 articles were included in the meta-analysis with data from 439 818 participants. The overall average SIB prevalence was 16.0% in these studies. The first hypothesis was only partially confirmed. When all data that were published between 2015 and 2018 were considered, x significant increase was found in the prevalence of SIB between 1998 and 2018. However, when the analysis was restricted to the time frame between 2013 and 2018, no change in prevalence was found. The second hypothesis was fulfilled, girls reported a significant higher prevalence than boys (19.4% and 12.9%, respectively). A significantly higher prevalence was found when suicidal intent was excluded (18.3%), than when it was not excluded (11.3%) from the definition of SIB. The largest prevalence was found when measurement instruments were used that had been validated for SIB (18.9%). A significantly higher SEB prevalence was found among Asian articles than those from other continents (19.5% and 14.7% respectively). Conclusions: The current systematic review and meta-analysis draw attention to the high prevalence of SIB among adolescents, especially among girls and those living in Asia. It is important to address this behavior, in terms of prevention and intervention as well. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Since its 2015 debut, Alex Garland’s Ex Machina has been conceptualized as a creation myth, as a succession myth, as the Pygmalion myth and as the Pandora myth, among others – each of these argumentations acknowledging the permeability between different interpretations. The author argues that Ex Machina recodes the myth of Pandora and creates a fertile ground to display cultural traumas that have been affecting women – such as female subordination and oppression caused by a patriarchal structure and stereotypical binary oppositions. Thus, Garland’s film also suggests that the old forms of female oppression might be reaffirmed in the context of the age of technological innovation.1

Moisture loss, weight change, and sorbitol uptake were measured including cryoprotection during freezing when chunks of freshwater trout muscle were immersed in sorbitol solutions. Various results obtained by other tests into fish muscle are evaluated.

This article discusses the accuracy of the PanMayo endoscopic score in predicting long-term disease outcomes in ulcerative colitis (UC). The study compared the PanMayo score to other scoring systems such as MES, UCEIS, and Dublin. The results showed that the PanMayo score was positively associated with the risk of flare-up, the need for new biological treatment, and treatment escalation. It was also associated with the risk of colectomy in patients with active disease. The study suggests that the combined endoscopic assessment provided by the PanMayo score may be more precise in predicting disease outcomes in UC. [Extracted from the article]