A screening program directed to find new agents against Leishmania donovani, the parasite causing visceral leishmaniasis, revealed that paullones attenuate the proliferation of axenic amastigotes. Because these structures were not active in a test system involving infected macrophages, a structure optimization campaign was carried out. Concomitant introduction of an unsaturated side chain into the 2-position and a tert-butyl substituent into the 9-position of the parent scaffold led to compounds inhibiting also parasites dwelling in macrophages. By inclusion of the so elaborated scaffold into a chalcone substructure, the toxicity against uninfected host cells was significantly reduced. For the synthesis of this new compound class, a novel modification of the Heck-type palladium-catalyzed C,C-cross coupling strategy was used, employing a ketone Mannich base as precursor for the alkene reactant. The so-prepared compounds exhibited improved antileishmanial activity both on axenic amastigotes (GI50 < 1 microM) as well as on parasites in infected macrophages.
Inhibitory control underlies one’s ability to maintain goal-directed behavior by inhibiting prepotent responses or ignoring irrelevant information. Recent models suggest that impaired inhibition of negative information may contribute to depressive symptoms, and that this association is mediated by rumination. However, the exact nature of this association, particularly in non-clinical samples, is unclear. The current study assessed the relationship between inhibitory control over emotional vs. non-emotional information, rumination and depressive symptoms. A non-clinical sample of 119 participants (mean age: 36.44 ± 11.74) with various levels of depressive symptoms completed three variations of a Go/No-Go task online; two of the task variations required either explicit or implicit processing of emotional expressions, and a third variation contained no emotional expressions (i.e., neutral condition). We found reductions in inhibitory control for participants reporting elevated symptoms of depression on all three task variations, relative to less depressed participants. However, for the task variation that required implicit emotion processing, depressive symptoms were associated with inhibitory deficits for sad and neutral, but not for happy expressions. An exploratory analysis showed that the relationship between inhibition and depressive symptoms occurs in part through trait rumination for all three tasks, regardless of emotional content. Collectively, these results indicate that elevated depressive symptoms are associated with both a general inhibitory control deficit, as well as affective interference from negative emotions, with implications for the assessment and treatment of mood disorders.
Background
During the COVID-19 pandemic, which enforced social distancing and isolation, teachers were required to handle multiple challenges related to their work, including dealing with remote teaching, in addition to personal, medical and financial challenges. The goal of the current research was to examine factors that contributed to professional burnout and commitment to work among teachers during the first and second waves of the COVID-19 pandemic.
Methods
A total of 344 elementary school teachers in Israel completed online self-report questionnaires, including assessments of stressors, anxiety, resilience, self-efficacy beliefs, and coping strategies. Structured Equation Modeling [SEM] was used to examine the contribution of these factors to professional burnout and commitment.
Results
The gaps between needed and received support had a direct effect on teachers’ burnout and commitment, and an indirect effect through anxiety and self-efficacy beliefs. Stress relating to remote teaching and support-gaps regarding remote teaching were the most significant of all the stressors and sources of support.
Conclusions
Collectively, these findings highlight the significance of remote teaching as the main cause of stress and professional burnout and suggest that proper preparation of teachers—before and during times of crisis, may have a significant impact on their mental and professional well-being.
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