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1.
J Transl Med ; 16(1): 84, 2018 04 03.
Article in English | MEDLINE | ID: mdl-29615090

ABSTRACT

BACKGROUND: Mental illness contributes substantially to global disease burden, particularly when illness onset occurs during youth and help-seeking is delayed and/or limited. Yet, few mental health promotion interventions target youth, particularly those with or at high risk of developing mental illness ("at-risk" youth). Community-based translational research has the capacity to identify and intervene upon barriers to positive health outcomes. This is especially important for integrated care in at-risk youth populations. METHODS: Here the Integrated Science Education Outreach (InSciEd Out) program delivered a novel school-based anti-stigma intervention in mental health to a cohort of seventh and eighth grade at-risk students. These students were assessed for changes in mental health knowledge, stigmatization, and help-seeking intentions via a classroom activity, surveys, and teacher interviews. Descriptive statistics and Cohen's d effect sizes were employed to assess pre-post changes. Inferential statistical analyses were also conducted on pilot results to provide a benchmark to inform future studies. RESULTS: Elimination of mental health misconceptions (substance weakness p = 0.00; recovery p = 0.05; prevention p = 0.05; violent p = 0.05) was accompanied by slight gains in mental health literacy (d = 0.18) and small to medium improvements in help-seeking intentions (anxiety d = 0.24; depression d = 0.48; substance d = 0.43; psychosis d = 0.53). Within this particular cohort of students, stigma was exceptionally low at baseline and remained largely unchanged. Teacher narratives revealed positive teacher views of programming, increased student openness to talk about mental illness, and higher peer and self-acceptance of mental health diagnoses and help-seeking. CONCLUSIONS: Curricular-based efforts focused on mental illness in an alternative school setting are feasible and integrated well into general curricula under the InSciEd Out framework. Preliminary data suggest the existence of unique help-seeking barriers in at-risk youth. Increased focus upon community-based programming has potential to bridge gaps in translation, bringing this critical population to clinical care in pursuit of improved mental health for all. Trial registration ClinicalTrials.gov, ID:NCT02680899. Registered 12 February 2016, https://clinicaltrials.gov/ct2/show/NCT02680899.


Subject(s)
Health Education , Mental Health , Schools , Adolescent , Female , Health Knowledge, Attitudes, Practice , Humans , Interviews as Topic , Male , Patient Acceptance of Health Care , Social Stigma , Surveys and Questionnaires
2.
PLoS One ; 10(6): e0130688, 2015.
Article in English | MEDLINE | ID: mdl-26110643

ABSTRACT

Skin disorders are widespread, but available treatments are limited. A more comprehensive understanding of skin development mechanisms will drive identification of new treatment targets and modalities. Here we report the Zebrafish Integument Project (ZIP), an expression-driven platform for identifying new skin genes and phenotypes in the vertebrate model Danio rerio (zebrafish). In vivo selection for skin-specific expression of gene-break transposon (GBT) mutant lines identified eleven new, revertible GBT alleles of genes involved in skin development. Eight genes--fras1, grip1, hmcn1, msxc, col4a4, ahnak, capn12, and nrg2a--had been described in an integumentary context to varying degrees, while arhgef25b, fkbp10b, and megf6a emerged as novel skin genes. Embryos homozygous for a GBT insertion within neuregulin 2a (nrg2a) revealed a novel requirement for a Neuregulin 2a (Nrg2a)-ErbB2/3-AKT signaling pathway governing the apicobasal organization of a subset of epidermal cells during median fin fold (MFF) morphogenesis. In nrg2a mutant larvae, the basal keratinocytes within the apical MFF, known as ridge cells, displayed reduced pAKT levels as well as reduced apical domains and exaggerated basolateral domains. Those defects compromised proper ridge cell elongation into a flattened epithelial morphology, resulting in thickened MFF edges. Pharmacological inhibition verified that Nrg2a signals through the ErbB receptor tyrosine kinase network. Moreover, knockdown of the epithelial polarity regulator and tumor suppressor lgl2 ameliorated the nrg2a mutant phenotype. Identifying Lgl2 as an antagonist of Nrg2a-ErbB signaling revealed a significantly earlier role for Lgl2 during epidermal morphogenesis than has been described to date. Furthermore, our findings demonstrated that successive, coordinated ridge cell shape changes drive apical MFF development, making MFF ridge cells a valuable model for investigating how the coordinated regulation of cell polarity and cell shape changes serves as a crucial mechanism of epithelial morphogenesis.


Subject(s)
Animal Fins/embryology , Neuregulins/metabolism , Oncogene Proteins v-erbB/metabolism , Organogenesis/genetics , Skin/embryology , Zebrafish Proteins/metabolism , Zebrafish/embryology , Alleles , Animal Fins/metabolism , Animals , Gene Expression Regulation, Developmental , Mutagenesis, Insertional , Neuregulins/genetics , Oncogene Proteins v-erbB/genetics , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/genetics , Skin/metabolism , Zebrafish/genetics , Zebrafish/metabolism , Zebrafish Proteins/genetics
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