Associations of psychological factors, parental involvement, and adverse health behaviors with bullying among tunisian middle school students.

BACKGROUND: Bullying is a serious problem that significantly affect adolescent well-being and health, needing the attention of teachers, school administrators, parents and public health professionals. In this study, we aimed at estimating the prevalence of bullying, from the perspective of victims in middle school students in the region of Monastir Tunisia, as well as analyzing its association with individual and family context variables. METHODS: This is a cross-sectional study conducted in December 2017 and January 2018 among a sample of students from two middle schools in the region of Monastir (Tunisia), using the Global School-based Student Health Survey (GSHS) self-answered questionnaire. We defined bullying victimization as being bullied in at least one day in the previous 30 days. Binary logistic regression model was used to identify factors associated with being bullied. RESULTS: Out of 802 students included in this study, nearly half (43.4%) reported having been bullied in the past month with CI 95%: 38.9-48.2. Gender did not interact with this behavior: (44.5%; CI 95%: 38.1-51.7) in boys versus (43.4% ; CI 95%: 37.2-50.2) in girls. Univariate analysis indicated significant differences regarding some individual factors such as physical fight, cigarette smoking, feeling lonely and being worried, in terms of prevalence of being bully victims. There were no significant differences in parental factors between the two groups (being bullied or not). Multivariate analysis showed the following factors as independently associated with bullying: being involved in physical fight (OR = 2.4; CI95%:1.77-3.25), feeling lonely (OR = 3.38; CI95% :2.04-5.57) and being worried (OR = 2.23; CI 95%:1.44-3.43). CONCLUSION: Bullying victimization was common among school-going adolescents and was linked with physical fight and psychosocial distress. This study highlights the need for school-based violence prevention programs to address this problem among the students.

Prediction of cardiovascular events in primary Health care: a cross sectional study (Monastir-Tunisia).

INTRODUCTION: We aimed to determine the prediction of cardiovascular events in patients with hypertension and diabetes using the 10-year Framingham score. METHODS: We conducted a cross sectional study in two primary health care centers in Monastir. We included patients with at least one conventional cardiovascular factors. Prediction of cardiovascular event were expressed by median and inter quartile range. RESULTS: We included 409 patients. Age mean was 64 years (SD: 12.3), the sex ratio was 0.44. Patients with type 2 Diabetes were 278 (68%) and 295 had hypertension (72.1%). The global risk prediction at 10 years for cardiovascular diseases was 26.3%, It was 36.6% (26.4-46.8) for tobacco users, 29.7% (18.2-42.5) for patients with hypertension and 29.1 % (18.8-43.3) for those with diabetes. It increased significantly with the number of cardiovascular risk factors. The risk prediction for cardiovascular events, were significantly higher in men than in women (p < 0.01) and in non-controlled patients than in controlled patients (p <0.001). The risk prediction for cardiovascular diseases death was 3.6% (1.3-8.6). CONCLUSION: Thirty percent of patients with hypertension or diabetes will develop cardiovascular diseases in 10 years. We suggest renforcing preventive actions to balance cardiovascular risk factors, including hypertension and diabetes.

Impact of social violence and childhood adversities on pregnancy outcomes: a longitudinal study in Tunisia.

BACKGROUND: Accumulating research suggests that exposure to intra-familial adversities are significant risk factors for adverse pregnancy outcomes. However, the relationship between social violence (peer violence, witnessing community violence and exposure to collective violence) and pregnancy outcomes has not been extensively investigated. Our study aims to examine the association between social Adverse Childhood Experiences (ACEs) and pregnancy outcomes and to explore the role of depression during pregnancy as a mediator of this association. METHODS: We performed a prospective follow-up study of pregnant women in five Primary Health care Centers (PHC) in the region of Monastir (Tunisia) from September 2015 to August 2016. Enrolled women were followed during the second trimester, third trimester of pregnancy and during the postnatal period. Exposure to violence was assessed retrospectively using the validated Arabic version of the World Health Organization (WHO) ACE questionnaire. The Self Reporting Questionnaire 20-Item (SRQ-20) was used as a screening tool for depression during pregnancy. RESULTS: We recruited and followed a total of 593 women during the study period. Witnessing community violence was the most frequently reported social ACE among pregnant women (237; 40%), followed by peer violence (233; 39.3%). After adjustment for high risk pregnancies, environmental tobacco smoke, and intra-familial ACEs, the risk of premature birth was significantly associated with exposure to collective violence (P < 0.001) and witnessing community violence (P < 0.05). The risk of low birth weight was significantly associated with witnessing community violence (P < 0.001). In the mediation analysis, depression mediated significant proportions of the relationship between the cumulative number of ACEs and pregnancy outcomes. CONCLUSIONS: Social ACEs may have a long-term effect on maternal reproductive health, as manifested by offspring that were of reduced birth weight and shorter gestational age. A public health framework based on the collaboration between pediatric, psychiatric obstetrical health professionals, education professionals and policy makers could be applied to ensure primary prevention of childhood adversities and pay attention to expected mothers with history of exposure to such adversities.

New Phage Display-Isolated Heptapeptide Recognizing the Regulatory Carboxy-Terminal Domain of Human Tumour Protein p53.

The transcription factor tumor protein p53 (P53) controls a variety of genes most involved in cell cycle and is at the origin of apoptosis when DNA is irreparably damaged. We planned to select novel tumor protein p53-interacting peptides through the screening of hepta-peptide phage-display libraries. For this aim, human tumor suppressor protein p53 was expressed in Escherichia coli as Glutathione S-transferase fusion and purified by affinity chromatography. The phage library was then screened on this immobilized protein target. After three rounds of panning, phages were sequenced and shown to contain a consensus sequence NPNSAQG. Thereafter, either free p53 liberated from the fusion protein through thrombin treatment or Histidine-tagged p53 were recognized efficiently by the selected phage. To locate the p53-binding epitope of the selected hepta-peptide, three long peptides parts of the three known domains of the protein were synthesized and screened by the selected phage/peptide. Thus, the Carboxy-terminal p53 region was shown to be the target of the isolated phage as well as by its derived Fluorescein isothiocyanate-peptide. Molecular docking showed Lysine 386 as an important residue potentially engaged in this interaction. The selected hepta-peptide is a novel p53-interacting peptide, not described by other studies, and could be used as therapeutic tool in the future.

Overexpression of yeast thioredoxin TRX2 reduces p53-mediated cell death in yeast.

We have previously shown that overexpression of the human tumor suppressor protein P53 causes cell death of the yeast Saccharomyces cerevisiae. P53 overproduction led to transcriptional downregulation of some yeast genes, such as the TRX1/2 thioredoxin system, which plays a key role in cell protection against various oxidative stresses induced by reactive oxygen species (ROS). In the present work, the impact of TRX2 overexpression on apoptosis mediated by p53 overexpression in yeast is investigated. In yeast cells expressing P53 under an inducible promoter together with TRX2 under a strong constitutive promoter, we showed that Tr2p overproduction reduced the apoptotic effect exerted by P53 and increased the viability of the P53-overproducing cells. Furthermore, measurements of ROS amounts by flow cytometry and fluorescence microscopy indicated that the TRX2 protein acted probably through its increased detoxifying activity on the P53-generated ROS. The steady-state level and activity of P53 were not affected by TRX2 overexpression, as shown by western blotting and functional analysis of separated alleles in yeast (FASAY), respectively. The growth inhibitory effect of P53 was partially reversed by the antioxidant N-acetylcysteine. Our data strengthen the idea that overexpression of a single gene (trx2) decreases the p53-mediated cell death by decreasing ROS accumulation.

Yeasts as a tool for heterologous gene expression.

The yeasts Saccharomyces cerevisiae and Pichia pastoris are attractive hosts for production of human proteins. The main advantages offered by these systems are the well-developed and easily accessible genetic tools, rapid growth, the simple and inexpensive culture media, and many of the cellular and metabolic processes found in higher eukaryotes are conserved in both yeast species. In this chapter, we describe the production of two proteins of therapeutic interest: the human P53 tumor suppressor and the viral HBsAg in P. pastoris and S. cerevisiae using the strong and inducible promoters AOX1 and Gal10/Cyc1, respectively. Besides the production as a goal of both expressions, we also report on an unexpected result that has occurred in S. cerevisiae: The overexpression of human p53 induces yeast cell death with characteristic markers of apoptosis, such as the externalization of phosphatidylserines and DNA strand cleavage.

Selection of cell death-deficient p53 mutants in Saccharomyces cerevisiae.

The budding yeast Saccharomyces cerevisiae is a useful system for the detection and transcriptional evaluation of mutant p53 in cancer. In previous work we showed that the overexpression of wild-type p53 induces yeast cell death on minimal medium; however, the R248W p53 mutant was completely inactive, and we suggested that ROS production is a key event in p53-induced yeast cell death. In this study we explored the effect of other p53 mutants, such as the hot-spot mutant R282W and the double mutant N268S::I332V. Unexpectedly, both mutants behaved inversely to R248W, as they completely inhibited yeast growth on minimal medium and induced ROS production. This phenotype 'yeast cell death on minimal medium' allowed for the subsequent screening of intragenic p53-inactivating mutations. In all cases, the 'revertant yeast clones' display a complete p53 inactivation through either gross deletion or nonsense mutations. More interestingly, missense mutations were also found: the deletion of I255 or substitution of R337G completely inactivated the p53 mutant R282W in the yeast context. Taken together, these results suggest that p53 tumour-derived mutants could be classified according to their ability to induce yeast cell death and not uniquely by their transcriptional activity on a selected target reporter gene.

Human p53 induces cell death and downregulates thioredoxin expression in Saccharomyces cerevisiae.

The p53 tumour suppressor protein has a crucial role in controlling cell cycle and apoptosis in human cells and its inactivation by selective point mutations is associated with human cancers. Here we show that overexpression of the human wild-type (wt) p53 in Saccharomyces cerevisiae completely inhibits yeast growth under minimal media conditions. In contrast, the R248W 'hot spot' p53 mutant (one of the most frequent p53 mutations encountered in human cancers) does not impair yeast growth. Moreover, we report, for the first time, that the human wt p53 induces yeast cell death with characteristic markers of apoptosis: exposure of phosphatidylserine and DNA strand cleavage as shown by Annexin V staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay, respectively. In addition, p53 also has an impact on the expression of yeast genes. Using differential display and Northern blot analysis, we demonstrated that human wt p53 expression in yeast leads to gene repression of thioredoxin (TRX1/2), a highly conserved multifunctional antioxidative and antiapoptotic protein family. Accordingly, we demonstrated that reactive oxygen species (ROS) are highly produced in p53 yeast induced cell death as shown by dihydrorhodamine 123 staining. These results suggest that the generation of ROS is a key event in p53 yeast induced cell death.