A school-based program to prevent depressive symptoms and strengthen well-being among pre-vocational students (Happy Lessons):protocol for a cluster randomized controlled trial and implementation study

BACKGROUND: Depression is one of the leading causes of illness and disability among young people. In the Netherlands, one in twelve Dutch adolescents has experienced depression in the last 12 months. Pre-vocational students are at higher risk for elevated depressive symptoms. Effective interventions, especially for this risk group, are therefore needed to prevent the onset of depression or mitigate the adverse long-term effects of depression. The aim of this study is to examine the effectiveness and implementation of a school-based program Happy Lessons (HL), that aims to prevent depression and promote well-being among pre-vocational students. METHODS: A cluster randomized controlled trial (RCT) with students randomized to HL or to care as usual will be conducted. Pre-vocational students in their first or second year (aged 12 to 14) will participate in the study. Subjects in both conditions will complete assessments at baseline and at 3- and 6-months follow-up. The primary outcome will be depressive symptoms using the Center for Epidemiologic Studies Depression Scale (CES-D) at 6-months follow-up. Secondary outcomes are well-being using the Warwick-Edinburgh Mental Well-Being Scale (WEMWBS) and life satisfaction (Cantril Ladder) measured at 6-months follow-up. Alongside the trial, an implementation study will be conducted to evaluate the implementation of HL, using both quantitative and qualitative methods (interviews, survey, and classroom observations). DISCUSSION: The results from both the RCT and implementation study will contribute to the limited evidence base on effective school-based interventions for the prevention of depression and promotion of well-being among pre-vocational adolescents. In addition, insights from the implementation study will aid identifying factors relevant for optimizing the future implementation and scale-up of HL to other schools and contexts. TRIAL REGISTRATION: This study was registered on 20 September 2021 in the Dutch Trial Register (NL9732). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-021-12321-3

Plasmodesmal connectivity in C₄ Gynandropsis gynandra is induced by light and dependent on photosynthesis

In leaves of C₄ plants the reactions of photosynthesis become restricted between two compartments. Typically, this allows accumulation of C₄ acids in mesophyll cells and subsequent decarboxylation in the bundle sheath. In C₄ grasses proliferation of plasmodesmata between these cell types is thought to increase cell-to-cell connectivity to allow efficient metabolite movement. However, it is not known if C₄ dicotyledons also show this enhanced plasmodesmal connectivity and so whether this is a general requirement for C₄ photosynthesis is not clear. How mesophyll and bundle sheath cells in C₄ leaves become highly connected is also not known. We investigated these questions using 3D- and 2D- electron microscopy on the C₄ dicotyledon Gynandropsis gynandra as well as phylogenetically close C₃ relatives. The mesophyll-bundle sheath interface of C₄ G. gynandra showed higher plasmodesmal frequency compared with closely related C₃ species. Formation of these plasmodesmata was induced by light. Pharmacological agents that perturbed chloroplast development or photosynthesis reduced the number of plasmodesmata, but this inhibitory effect could be reversed by the provision of exogenous sucrose. We conclude that enhanced formation of plasmodesmata between mesophyll and bundle sheath cells is wired to the induction of photosynthesis in C₄ G. gynandra

Plasmodesmal connectivity in C4 Gynandropsis gynandra is induced by light and dependent on photosynthesis.

Publication status: PublishedIn leaves of C4 plants, the reactions of photosynthesis become restricted between two compartments. Typically, this allows accumulation of C4 acids in mesophyll (M) cells and subsequent decarboxylation in the bundle sheath (BS). In C4 grasses, proliferation of plasmodesmata between these cell types is thought to increase cell-to-cell connectivity to allow efficient metabolite movement. However, it is not known whether C4 dicotyledons also show this enhanced plasmodesmal connectivity and so whether this is a general requirement for C4 photosynthesis is not clear. How M and BS cells in C4 leaves become highly connected is also not known. We investigated these questions using 3D- and 2D-electron microscopy on the C4 dicotyledon Gynandropsis gynandra as well as phylogenetically close C3 relatives. The M-BS interface of C4 G. gynandra showed higher plasmodesmal frequency compared with closely related C3 species. Formation of these plasmodesmata was induced by light. Pharmacological agents that perturbed photosynthesis reduced the number of plasmodesmata, but this inhibitory effect could be reversed by the provision of exogenous sucrose. We conclude that enhanced formation of plasmodesmata between M and BS cells is wired to the induction of photosynthesis in C4 G. gynandra

Diversity-oriented synthesis yields novel multistage antimalarial inhibitors

Antimalarial drugs have thus far been chiefly derived from two sources—natural products and synthetic drug-like compounds. Here we investigate whether antimalarial agents with novel mechanisms of action could be discovered using a diverse collection of synthetic compounds that have three-dimensional features reminiscent of natural products and are underrepresented in typical screening collections. We report the identification of such compounds with both previously reported and undescribed mechanisms of action, including a series of bicyclic azetidines that inhibit a new antimalarial target, phenylalanyl-tRNA synthetase. These molecules are curative in mice at a single, low dose and show activity against all parasite life stages in multiple in vivo efficacy models. Our findings identify bicyclic azetidines with the potential to both cure and prevent transmission of the disease as well as protect at-risk populations with a single oral dose, highlighting the strength of diversity-oriented synthesis in revealing promising therapeutic targets