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Background: The failure to regulate emotions, namely emotional dysregulation (ED), is a relevant construct in adolescent psychiatry, in terms of prognostic and developmental implications. We developed and validated a novel self-report questionnaire for the assessment of ED, the RIPoSt-Y, both in clinical and non-clinical samples.Methods: Items selection and subscales construction were conducted on healthy controls (n=374), while test-retest reliability was evaluated in a subsample (n=72); internal consistency was examined both in the control group and in two clinical samples, respectively including patients with Bipolar Spectrum Disorders (BSD; n=44) and ADHD (n=34). Construct, concurrent and convergent validity were also assessed.Results: Thirty-one items were finally retained, and three subscales were identified (Affective Instability, Emotional Reactivity, Interpersonal Sensitivity). Test-retest was significant for each subscale with moderate-to-good correlations, and internal consistency showed good-to-excellent coefficients. Construct validity was supported by significant differences between patients and controls and gender-related differences. Concurrent validity was confirmed through significant associations with two subscales of the CHT-Q, while convergent validity proved to be significant with the CBCL/YSR dysregulation-profile. Cut-offs were also computed to discriminate clinically significant scores of ED.Limitations: The use of a school-based survey to recruit controls could have biased our results; gender distributions between clinical and non-clinical samples were significantly different.Conclusions: Our novel questionnaire proved to be a valid and reliable tool able to assess the presence of ED in youths and to characterize this fundamental construct in its multidimensional facets. [ABSTRACT FROM AUTHOR]

Plakortin, a polyketide endoperoxide from the sponge Plakortis simplex has antiparasitic activity against P. falciparum . Similar to artemisinin, its activity depends on the peroxide functionality. Plakortin induced stage-, dose- and time-dependent morphologic anomalies, early maturation delay, ROS generation and lipid peroxidation in the parasite. Ring damage by 1 and 10 µM plakortin led to parasite death before schizogony at 20 and 95%, respectively. Treatment of late schizonts with 1, 2, 5 and 10 µM plakortin resulted in decreased reinfection rates by 30, 50, 61 and 65%, respectively. In both rings and trophozoites, plakortin induced a dose- and time-dependent ROS production as well as a significant lipid peroxidation and up to 4-fold increase of the lipoperoxide breakdown product 4-hydroxynonenal (4-HNE). Antioxidants and the free radical scavengers trolox and N-acetylcysteine significantly attenuated the parasite damage. Plakortin generated 4-HNE conjugates with the P. falciparum proteins: heat shock protein Hsp70-1, endoplasmatic reticulum-standing Hsp70-2 (BiP analogue), V-type proton ATPase catalytic subunit A, enolase, the putative vacuolar protein sorting-associated protein 11, and the dynein heavy chain-like protein, whose specific binding sites were identified by mass spectrometry. These proteins are crucially involved in protein trafficking, transmembrane and vesicular transport and parasite survival. We hypothesize that binding of 4-HNE to functionally relevant parasite proteins may explain the observed plakortin-induced morphologic aberrations and parasite death. The identification of 4-HNE-protein conjugates may generate a novel paradigm to explain the mechanism of action of pro-oxidant, peroxide-based antimalarials such as plakortin, artemisinins and synthetic endoperoxides. [ABSTRACT FROM AUTHOR]