Educational activities of secondary school students in Serbia: A time-diary analysis

The aim of this study was to determine the time allocation of various educational activities within the structure of a typical day of Serbian secondary school students, and whether there were significant differences in this respect depending on their socio-demographic characteristics. The 24-hour time diary method was applied: the subjects described chronologically, at half-hourly intervals, their activities in one weekday an done weekend day. The research was conducted on a sample of 922 secondary school students, Structured by region, age and type of school. The analysis revealed that on weekdays students spent about 5 hours in school. In work activities outside school they spent almost 2 hours, out of which the largest part in learning (81 minutes), and significantly less in housework (23 minutes) and economically productive work (7 minutes). From a total of5 hours and22 minutes of free time, only 5 minutes were devoted to organized extracurricular activities. Significant differences were obtained with regard to students’ gender, type of school, and level of parents’ education. When these results are compared with the data from other countries, it is shown that secondary school students in Serbia, compared to the U.S., spend more time in learning, and significantly less in economically productive work and house­work, much like the youth in European countries. A very low proportion of extracurricular activities shows that school learning is almost the only context of developing educational competencies. The implications of these findings are discussed from the perspective of positive youth development. [Projekat Ministarstva nauke Republike Srbije: Identifikacija, merenje i razvoj kognitivnih i emocionalnih kompetencija važnih društvu orijentisanom na evropske integracije

A Deficiência de vitamina d está associada com níveis aumentados de il-17 e tnfα em pacientes com insuficiência cardíaca crônica

FUNDAMENTO: Estudos recentes revelaram uma forte associação entre o estado de vitamina D (VD) e a insuficiência cardíaca crônica (ICC). Hoje, é normalmente aceito que a resposta imune pró-inflamatória é subjacente ao desenvolvimento de ICC. OBJETIVO: Uma vez que a VD possui propriedades anti-inflamatórias, pesquisamos o seu impacto sobre as citocinas envolvidas na ICC, como TNFα e IL-17, em pacientes portadores de ICC. MÉTODOS: Foi extraído sangue de quarenta pacientes com ICC secundária à hipertensão arterial e/ou doença coronariana. Os níveis de VD status, IL-17 e TNFαforam avaliados através de 25-hidroxi VD3 EIA e ELISA de citocinas. Também foram realizadas avaliação clínica e ecocardiograma. RESULTADOS: Pacientes idosos com ICC em Nis (Sudeste da Europa, latitude 43ºN) apresentaram níveis de 25-hidroxi VD3 abaixo do normal. Nossos dados demonstraram que pacientes com ICC secundária à hipertensão arterial têm níveis significativamente menores de 25-hidroxi VD3, e maiores de TNFαe IL-17A, se comparados com os níveis de pacientes com ICC secundária à doença coronariana. CONCLUSÃO: É demonstrado aqui que, mesmo em regiões com muitos dias ensolarados a deficiência de VD é motivo de preocupação. Os dados sugerem que o déficit de VD contribui para os elevados níveis de IL-17 e TNFα e, assim, contribuir ao desenvolvimento de ICC

Tracing the origin and dynamics of the HIV-1 epidemic in Serbia

Since the first report of HIV infection in Serbia in 1985, the HIV-1 epidemic was very dynamic, changing the pattern in subtype distribution and prevailing transmission routes. To better understand the origin and epidemiological dynamics of HIV-1, we analyzed 266 (pol) sequences from Serbian patients diagnosed over a period of 14 years. Subtype distribution in Serbia is still marked by a prevailing subtype B genetic form. The transmission pattern, however, has changed from being intravenous drug user (IVDU) - driven to predominantly sexual transmission. The estimated time of initial founder strain introduction of sequences from Serbian IVDUs and MSM (men who have sex with men) is similar and dates back to the early 1980s, while introduction of subtype C occurred much more recently. [Projekat Ministarstva nauke Republike Srbije, br. 175024

AKT-dependent NOTCH3 activation drives tumor progression in a model of mesenchymal colorectal cancer

Recently, a transcriptome-based consensus molecular subtype (CMS) classification of colorectal cancer (CRC) has been established, which may ultimately help to individualize CRC therapy. However, the lack of animal models that faithfully recapitulate the different molecular subtypes impedes adequate preclinical testing of stratified therapeutic concepts. Here, we demonstrate that constitutive AKT activation in intestinal epithelial cells markedly enhances tumor invasion and metastasis in Trp53ΔIEC mice (Trp53ΔIECAktE17K) upon challenge with the carcinogen azoxymethane. Gene-expression profiling indicates that Trp53ΔIECAktE17K tumors resemble the human mesenchymal colorectal cancer subtype (CMS4), which is characterized by the poorest survival rate among the four CMSs. Trp53ΔIECAktE17K tumor cells are characterized by Notch3 up-regulation, and treatment of Trp53ΔIECAktE17K mice with a NOTCH3-inhibiting antibody reduces invasion and metastasis. In CRC patients, NOTCH3 expression correlates positively with tumor grading and the presence of lymph node as well as distant metastases and is specifically up-regulated in CMS4 tumors. Therefore, we suggest NOTCH3 as a putative target for advanced CMS4 CRC patients.status: publishe

Tolerizing CTL by sustained hepatic PD-L1 expression provides a new therapy approach in mouse sepsis

Cytotoxic T lymphocyte (CTL) activation contributes to liver damage during sepsis, but the mechanisms involved are largely unknown. Understanding the underlying principle will permit interference with CTL activation and thus, provide a new therapeutic option. Methods: To elucidate the mechanism leading to CTL activation we used the Hepa1-6 cell line in vitro and the mouse model of in vivo polymicrobial sepsis, following cecal-ligation and -puncture (CLP) in wildtype, myeloid specific NOX-2, global NOX2 and NOX4 knockout mice, and their survival as a final readout. In this in vivo setting, we also determined hepatic mRNA and protein expression as well as clinical parameters of liver damage - aspartate- and alanine amino-transaminases. Hepatocyte specific overexpression of PD-L1 was achieved in vivo by adenoviral infection and transposon-based gene transfer using hydrodynamic injection. Results: We observed downregulation of PD-L1 on hepatocytes in the murine sepsis model. Adenoviral and transposon-based gene transfer to restore PD-L1 expression, significantly improved survival and reduced the release of liver damage, as PD-L1 is a co-receptor that negatively regulates T cell function. Similar protection was observed during pharmacological intervention using recombinant PD-L1-Fc. N-acetylcysteine blocked the downregulation of PD-L1 suggesting the involvement of reactive oxygen species. This was confirmed in vivo, as we observed significant upregulation of PD-L1 expression in NOX4 knockout mice, following sham operation, whereas its expression in global as well as myeloid lineage NOX2 knockout mice was comparable to that in the wild type animals. PD-L1 expression remained high following CLP only in total NOX2 knockouts, resulting in significantly reduced release of liver damage markers. Conclusion: These results suggest that, contrary to common assumption, maintaining PD-L1 expression on hepatocytes improves liver damage and survival of mice during sepsis. We conclude that administering recombinant PD-L1 or inhibiting NOX2 activity might offer a new therapeutic option in sepsis

Tolerizing CTL by sustained hepatic PD-L1 expression provides a new therapy spproach in mouse sepsis

Cytotoxic T lymphocyte (CTL) activation contributes to liver damage during sepsis, but the mechanisms involved are largely unknown. Understanding the underlying principle will permit interference with CTL activation and thus, provide a new therapeutic option. Methods: To elucidate the mechanism leading to CTL activation we used the Hepa1-6 cell line in vitro and the mouse model of in vivo polymicrobial sepsis, following cecal-ligation and -puncture (CLP) in wildtype, myeloid specific NOX-2, global NOX2 and NOX4 knockout mice, and their survival as a final readout. In this in vivo setting, we also determined hepatic mRNA and protein expression as well as clinical parameters of liver damage - aspartate- and alanine amino-transaminases. Hepatocyte specific overexpression of PD-L1 was achieved in vivo by adenoviral infection and transposon-based gene transfer using hydrodynamic injection. Results: We observed downregulation of PD-L1 on hepatocytes in the murine sepsis model. Adenoviral and transposon-based gene transfer to restore PD-L1 expression, significantly improved survival and reduced the release of liver damage, as PD-L1 is a co-receptor that negatively regulates T cell function. Similar protection was observed during pharmacological intervention using recombinant PD-L1-Fc. N-acetylcysteine blocked the downregulation of PD-L1 suggesting the involvement of reactive oxygen species. This was confirmed in vivo, as we observed significant upregulation of PD-L1 expression in NOX4 knockout mice, following sham operation, whereas its expression in global as well as myeloid lineage NOX2 knockout mice was comparable to that in the wild type animals. PD-L1 expression remained high following CLP only in total NOX2 knockouts, resulting in significantly reduced release of liver damage markers. Conclusion: These results suggest that, contrary to common assumption, maintaining PD-L1 expression on hepatocytes improves liver damage and survival of mice during sepsis. We conclude that administering recombinant PD-L1 or inhibiting NOX2 activity might offer a new therapeutic option in sepsis