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IntroductionDiscrimination towards people with schizophrenia (PWS) by healthcare professionals is responsible of underdiagnosis and undertreatment of these patients. Negative attitudes toward PSW in health care professionals tend to be present since their university studies and are related to their knowledge and experience about the disease.Objectives and aimsTo assess opinion towards PSW in medical, nursing and psychology students and to investigate the relation with their knowledge of schizophrenia and its causes.MethodsThe study involved 133 medical, 200 nursing and 296 psychology undergraduate students. The opinion on mental illness questionnaire, the Devaluation Consumers Scale, and the Devaluation of Consumer Families Scale were administered to the sample. ANOVA and ANCOVA were used to test differences between groups and the relation between causal explanation of schizophrenia and discrimination towards PWS.ResultsPsychology students were more aware than the other student of public stigma towards PWS and their families (F 12.57, P < 0.001; F 32.69, P < 0.001) and expressed a more positive view on treatments’ effectiveness (F 30.74, P < 0.001). Psychology (OR 0.48, 95% CI 0.26–0.88) and nursing (OR 0.29, 95% CI 0.15–0.55) students were more likely to identify psychological and social risk factors as more frequent causes of schizophrenia (vs. biogenetics) and these, in turn, were related to a better opinion towards social equality of PWS.ConclusionsThese preliminary findings underline the relevance of biopsychosocial model of schizophrenia within stigma-reduction programs for health science students.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Retinoic acid (RA) treatment of embryonal carcinoma cell line NTERA-2 clone D1 (NT2/D1) induces growth arrest and terminal differentiation along the neuronal pathway. In the present study, we provide a functional link between RA and p27 function in the control of neuronal differentiation in NT2/D1 cells. We report that RA enhances p27 expression, which results in increased association with cyclin E/cyclin-dependent kinase 2 complexes and suppression of their activity; however, antisense clones, which have greatly reduced RA-dependent p27 inducibility (NT2-p27AS), continue to synthesize DNA and are unable to differentiate properly in response to RA as determined by lack of neurite outgrowth and by the failure to modify surface antigens. As to the mechanism involved in RA-dependent p27 up-regulation, our data support the concept that RA reduces p27 protein degradation through the ubiquitin/proteasome-dependent pathway. Taken together, these findings demonstrate that in embryonal carcinoma cells, p27 expression is required for growth arrest and proper neuronal differentiation.

Hexamethylen-bisacetamide (HMBA) represents the prototype of a group of hybrid polar compounds, which induce differentiation in a variety of transformed cells including human embryonal carcinoma cells. Therefore, HMBA has been used in the differentiation therapy of cancer for patients with both hematological and solid malignancies. Upon HMBA treatment, the embryonal carcinoma cell line NTERA-2 clone D1 (NT2/D1) accumulates in G1 and undergoes terminal differentiation. Here we demonstrate that growth arrest and differentiation of NT2/D1 cells induced by HMBA involve increased expression of the cyclin-dependent kinase inhibitor p27, enhanced association of p27 with cyclin E/CDK2 complexes and suppression of kinase activity associated to cyclin E/CDK2 (but not to cyclin D3/CDK4). When HMBA differentiation was induced in the presence of p27 antisense oligonucleotides, NT2/D1 cells failed to arrest growth properly and, in parallel with the reduction of the anti-apoptotic Bcl-2 gene expression, cells underwent massive programmed cell death. Conversely, constitutive expression of p27 into NT2/D1 cells induced a marked reduction in the growth potential of these cells and partially reproduced HMBA-induced modification of surface antigen expression (down-regulation of SSEA-3 expression and up-regulation of VINIS-53 expression). Expression of p21 induced growth arrest but not differentiation. Likewise, inhibition of CDK2 by transfection of a dominant negative CDK2 in NT2/D1 cells or treatment with the kinase inhibitor olomucine induced growth arrest but not differentiation. Therefore, we propose that p27 represents a crucial molecule in HMBA signaling that cannot be replaced by p21. Furthermore, the results obtained with CDK2 inhibitors demonstrate that the block of CDK2 activity is sufficient for growth arrest but not for cell differentiation and suggest that, at least in these cells, growth arrest and differentiation are regulated by two overlapping but different pathways.