A DADA drogprevenciós program hatékonyságvizsgálata hetedik évfolyamos általános iskolai tanulók körében = Evaluation of the effectiveness of a DADA school-drug prevention program among seventh-grade students

Absztrakt: Bevezetés: A drogok fogyasztása a fiatalok körében nem ritka jelenség. Bizonyítottan hatékony iskolai drogprevenciós programokra van szükség. Célkitűzés: Kutatásunk célja a rendőrségi DADA drogprevenciós program hatékonyságának feltárása volt. Módszer: A kutatás a pécsi székhelyű Apáczai Csere János Általános Iskola és a pécsváradi Kodolányi János Általános Iskola diákjai körében végzett standard kérdőíves vizsgálaton alapult. Eredmények: A részt vevő diákok válaszait elemezve kiderült, hogy programot követően 27%-ról 37,3%-ra nőtt azok aránya, akik „mindent tudnak”, és 5,6%-ról 1,6%-ra csökkent azoké, akik „semmit sem tudnak” a drogokról (p<0,001). A DADA-program hatására nem mutatkozott szignifikáns változás az énhatékonyság tekintetében (p = 0,364). Azzal az állítással azonban, hogy „Nagyon sokat tanultam a foglalkozásból”, illetve „Sok olyan kérdésre kaptam választ, ami már régóta foglalkoztatott”, mindössze a diákok kevesebb mint 60%-a értett egyet. Következtetés: A DADA-program összességében eredményesnek bizonyult. A program hatékonyságának értékelésekor figyelembe kell vennünk a részt vevő diákok társadalmi és kulturális hátterét is. Orv Hetil. 2019; 160(23): 914–920. | Abstract: Introduction: Drug-taking habit is not infrequent in the young population. There is a need of proven effective drug prevention programs. Aim: The aim of our study was to analyze the efficiency of the Hungarian Police’s DADA school-drug prevention program. Method: The research program was carried out by a standard questionnaire at Apáczai Csere János Primary School in Pécs and Kodolányi János Primary School in Pécsvárad. Results: After analyzing the participating students’ answers, the results showed that the rate of those, who “know everything” about drugs, increased from 27% to 37.3%, and of those, who did “not know anything”, decreased from 5.6% to 1.6% (p<0.001). Regarding self-efficiency, the DADA program did not show any significant change (p = 0.364). However, less than 60% of the students agreed the statements: “I have learned a lot from the trainings” and “I received answers to several questions that I had been interested in earlier.” Conclusion: We can conclude that the DADA program was successful. Regarding the chosen reactions and opinions about the program, we have to consider the sociocultural background of the participants. Orv Hetil. 2019; 160(23): 914–920

Fibrosis related inflammatory mediators: Role of the IL-10 cytokine family

Importance of chronic fibroproliferative diseases (FDs) including pulmonary fibrosis, chronic kidney diseases, inflammatory bowel disease, and cardiovascular or liver fibrosis is rapidly increasing and they have become a major public health problem. According to some estimates about 45% of all deaths are attributed to FDs in the developed world. Independently of their etiology the common hallmark of FDs is chronic inflammation. Infiltrating immune cells, endothelial, epithelial, and other resident cells of the injured organ release an orchestra of inflammatory mediators, which stimulate the proliferation and excessive extracellular matrix (ECM) production of myofibroblasts, the effector cells of organ fibrosis. Abnormal amount of ECM disturbs the original organ architecture leading to the decline of function. Although our knowledge is rapidly expanding, we still have neither a diagnostic tool to detect nor a drug to specifically target fibrosis. Therefore, there is an urgent need for the more comprehensive understanding of the pathomechanism of fibrosis and development of novel diagnostic and therapeutic strategies. In the present review we provide an overview of the common key mediators of organ fibrosis highlighting the role of interleukin-10 (IL-10) cytokine family members (IL-10, IL-19, IL-20, IL-22, IL-24, and IL-26), which recently came into focus as tissue remodeling-related inflammatory cytokines

Metabolic syndrome influences cardiac gene expression pattern at the transcript level in male ZDF rats

Background: Metabolic syndrome (coexisting visceral obesity, dyslipidemia, hyperglycemia, and hypertension) is a prominent risk factor for cardiovascular morbidity and mortality, however, its effect on cardiac gene expression pattern is unclear. Therefore, we examined the possible alterations in cardiac gene expression pattern in male Zucker Diabetic Fatty (ZDF) rats, a model of metabolic syndrome. Methods: Fasting blood glucose, serum insulin, cholesterol and triglyceride levels were measured at 6, 16, and 25 wk of age in male ZDF and lean control rats. Oral glucose tolerance test was performed at 16 and 25 wk of age. At week 25, total RNA was isolated from the myocardium and assayed by rat oligonucleotide microarray for 14921 genes. Expression of selected genes was confirmed by qRT-PCR. Results: Fasting blood glucose, serum insulin, cholesterol and triglyceride levels were significantly increased, glucose tolerance and insulin sensitivity were impaired in ZDF rats compared to leans. In hearts of ZDF rats, 36 genes showed significant up-regulation and 49 genes showed down-regulation as compared to lean controls. Genes with significantly altered expression in the heart due to metabolic syndrome includes functional clusters of metabolism (e.g. 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2; argininosuccinate synthetase; 2-amino-3ketobutyrate-coenzyme A ligase), structural proteins (e.g. myosin IXA; aggrecan1), signal transduction (e. g. activating transcription factor 3; phospholipase A2; insulin responsive sequence DNA binding protein-1) stress response (e.g. heat shock 70kD protein 1A; heat shock protein 60; glutathione S-transferase Yc2 subunit), ion channels and receptors (e.g. ATPase, (Na+)/K+ transporting, beta 4 polypeptide; ATPase, H+/K+ transporting, nongastric, alpha polypeptide). Moreover some other genes with no definite functional clusters were also changed such as e. g. S100 calcium binding protein A3; ubiquitin carboxy-terminal hydrolase L1; interleukin 18. Gene ontology analysis revealed several significantly enriched functional inter-relationships between genes influenced by metabolic syndrome. Conclusions: Metabolic syndrome significantly alters cardiac gene expression profile which may be involved in development of cardiac pathologies in the presence of metabolic syndrome

Phylogeny of Mycoplasma bovis isolates from Hungary based on multi locus sequence typing and multiple-locus variable-number tandem repeat analysis

BACKGROUND: Mycoplasma bovis is an important pathogen causing pneumonia, mastitis and arthritis in cattle worldwide. As this agent is primarily transmitted by direct contact and spread through animal movements, efficient genotyping systems are essential for the monitoring of the disease and for epidemiological investigations. The aim of this study was to compare and evaluate the multi locus sequence typing (MLST) and the multiple-locus variable-number tandem repeat (VNTR) analysis (MLVA) through the genetic characterization of M. bovis isolates from Hungary. RESULTS: Thirty one Hungarian M. bovis isolates grouped into two clades by MLST. Two strains had the same sequence type (ST) as reference strain PG45, while the other twenty nine Hungarian isolates formed a novel clade comprising five subclades. Isolates originating from the same herds had the same STs except for one case. The same isolates formed two main clades and several subclades and branches by MLVA. One clade contained the reference strain PG45 and three isolates, while the other main clade comprised the rest of the strains. Within-herd strain divergence was also detected by MLVA. Little congruence was found between the results of the two typing systems. CONCLUSIONS: MLST is generally considered an intermediate scale typing method and it was found to be discriminatory among the Hungarian M. bovis isolates. MLVA proved to be an appropriate fine scale typing tool for M. bovis as this method was able to distinguish closely related strains isolated from the same farm. We recommend the combined use of the two methods for the genotyping of M. bovis isolates. Strains have to be characterized first by MLST followed by the fine scale typing of identical STs with MLVA

Role of IL-24 in the mucosal remodeling of children with coeliac disease

Background Recently, involvement of IL-19, IL-20 and IL-24 has been reported in inflammatory diseases associated with tissue remodeling. However, their impact on the pathomechanism of coeliac disease (CD) is still completely unknown. Methods Expression of IL19, IL20 and IL24 was measured by real-time RT-PCR, protein amount of IL-24, α smooth muscle actin (α-SMA) and fibronectin (FN) was determined by Western-blot analysis in the duodenal biopsies of therapy naive children with CD and controls. Localization of IL-24 and IL-20RB was investigated by immunofluorescent staining in the duodenal mucosa. Effect of recombinant IL-1β, TNF-α, TGF-β and IL-17 treatment on the expression of IL19, IL20, IL24 and their receptors was investigated by real-time RT-PCR in small intestinal epithelial cells (FHs74Int), in primary duodenal myofibroblasts (pdMFs) and in peripheral blood mononuclear cells (PBMCs). Effect of IL-24 on H2O2 treated FHs74Int cells and on pdMFs was measured by MTT, LDH, Annexin V assays, real-time RT-PCR and by fluorescent microscopy. Results We found increased level of IL-24 (3.3×, p < 0.05), α-SMA (2.4×, p < 0.05) and FN (2.3×, p < 0.05) in the duodenal mucosa and increased expression of IL19 (3.6×, p < 0.05) and IL24 (5.2×, p < 0.05) in the PBMCs of children with CD compared to that of controls. IL-1β was a strong inducer of IL24 expression of FHs74Int cells (9.9×, p < 0.05), pdMFs (552.9×, p < 0.05) or PBMCs (17.2×, p < 0.05), as well. IL-24 treatment reduced the number of apoptotic cells (0.5×, p < 0.05) and decreased the expression of inflammatory factors, including IL1A, IL6 and TNF of H2O2-treated FHs74Int cells. IL-24 decreased the proliferation (0.6×, p < 0.05) of PDGF-B treated pdMFs. Moreover, IL-24 treatment altered the morphology of pdMFs by influencing the size of the angles between stress fibers and the longitudinal axis of the cells (2.0×, p < 0.05) and the expression of cytoskeletal components, including ACTA2, ACTB, VIM, SNAI1 and SNAI2. Conclusion Our results suggest that IL-24 plays a significant role in the maintenance of duodenal mucosal integrity in CD

Új pathomechanizmusok és kezelési lehetőségek vizsgálata a vese ischémia/reperfúziós károsodásában és krónikus allograft nephropathiában = Investigation of new pathomechanisms and treatment possibilities of renal ischemia/reperfusion injury and chronic allograft nephropathy

Eredményeink az erythropoietin (EPO) védő szerepét igazolták egyoldali vese ischemia/reperfúziós (I/R) károsodásban. Ez a védő szerep elsősorban hímekben igazolható. Hátterében az EPO HSP72-mediálta hatása állhat, amellyel a Na+/K+ ATP-áz funkciójának megtartását segíti elő. Vizsgálataink során az EPO sejt-protektív hatásának hátterében egy új szignál molekulát is sikerült azonosítanunk, a szérum és glükokortikoid aktiválta kináz-1-t (SGK1). Ezek az eredmények az EPO által kifejtett sejtprotekció hátterében álló új pathomechanizmusokat írtak le. Eredményeink alapján az EPO, illetve a leírt útvonalakra ható egyéb szerek további vizsgálata és klinikai hasznosítása jöhet szóba. Másik vizsgálatunk során az I/R-s károsodás kivédésében szerepet játszó mechanizmusok során megfigyelhető nemi különbségeket írtuk le. Igazoltuk, hogy hímekben elsősorban a HIF 1α, míg nőstényekben a HSF útvonal tűnik fontosabbnak. Végül igazoltuk. hogy az SGK1 anti-apoptotikus és sejtvédő funkciójában is nemi különbségek mutathatók ki I/R-t követően. Ezekkel az eredményeinkkel magyarázhatóak az irodalomban korábban leírt és egymásnak ellentmondó közlések, amelyek a tesztoszteron SGK1 reguláló hatását mutatták be. | Our results suggest that EPO protects against severe, unilateral renal I/R injury, especially in male rats. This beneficial effect might be partly the result of EPO’s HSP72-mediated impact on Na+/K+ATPase-α1. Moreover, our data report a new signaling molecule to be involved in EPO cytoprotective actions, since we identified for the first time an important role of SGK1 in the renoprotective effect of EPO. These observations provide insights into a novel signaling mechanism by which EPO partly exerts its potent tissue protective actions. Given our results along with previous reports, the clinical use of EPO possibly leading to reduced cellular damage due to ischemic events should be considered. Our study has revealed a gender-dependent protective mechanism during renal I/R injury. In males mostly the HIF 1α, while in females the HSF is the dominant transcriptional pathway. The EPO treatment results in disappearance of the characteristic signal pathway activation in both genders. The explanation for that could be either a direct negative feedback effect on the transcription factors or an indirect renal protective effect of EPO by which these transcriptional factors do not need to be activated. We could also demonstrate that the anti-apoptotic SGK1 shows a gender-specific expression pattern after renal I/R with higher levels in male rats. These results confirm previous contradictory reports showing that SGK1 might be up-regulated and activated by testosterone

Unravelling the Role of Trophoblastic-Derived Extracellular Vesicles in Regulatory T Cell Differentiation

Regulatory T cells (Treg) are mandatory elements in the maintenance of human pregnancy, but their de novo differentiation has not been completely exposed. HSPE1 chaperone expressing trophoblast cells may have a role in it. Trophoblast-derived extracellular vesicles (EVs), either at the feto&ndash;maternal interface or in circulation, target CD4+ T cells. We hypothesized that HSPE1-associated trophoblastic cell line (BeWo)-derived EVs are active mediators of Treg cell differentiation. We proved at first that recombinant HSPE1 promote human Treg cell differentiation in vitro. Developing a CRISPR-Cas9 based HSPE1 knockout BeWo cell line we could also demonstrate, that EV-associated HSPE1 induces Treg development. Next-generation sequencing of miRNA cargo of BeWo-EVs characterized the regulatory processes of Treg polarization. By the use of single-cell transcriptomics analysis, seven Treg cell subtypes were distinguished and we demonstrated for the first time that the expression level of HSPE1 was Treg subtype dependent, and CAPG expression is characteristic to memory phenotype of T cells. Our data indicate that HSPE1 and CAPG may be used as markers for identification of Treg subtypes. Our results suggest, that trophoblastic-derived iEVs-associated HSPE1 and miRNA cargo have an important role in Treg cell expansion in vitro and HSPE1 is a useful marker of Treg subtype characterization

Density-Dependent Plant–Plant Interactions Triggered by Grazing

Plant species performance in rangelands highly depends on the effect of grazing and also on the occurrence of unpalatable benefactor species that can act as biotic refuges protecting neighboring plants from herbivores. The balance between facilitation and competition may changes with the benefactor density. Despite the high number of studies on the role of biotic refuges, the density dependent effects of unpalatable herbaceous plants on the performance of other species, and on the habitat heterogeneity of rangelands are still unclear. Therefore, we performed a study to test the following hypotheses: (i) Performances of understory species follow a humped-back relationship along the density gradient of the unpalatable benefactor species. (ii) Small-scale heterogeneity of the vegetation decreases with increasing benefactor density. We studied meadow steppes with medium intensity cattle grazing in Hungary. We surveyed understory species’ performance (number of flowering shoots and cover scores) along the density gradient of a common, native unpalatable species (Althaea officinalis). Our findings supported both hypotheses. We found unimodal relationship between the benefactor cover and both the flowering success and richness of understory species. Moreover, small-scale heterogeneity declined with increasing benefactor cover. In this study we detected a humped-back pattern of facilitation along the density gradient of an herbaceous benefactor in pastures. Indeed, this pattern was predictable based on such conceptual models like “consumer pressure-abiotic stress model,” “humped-back model,” “intermediate disturbance hypothesis,” and “disturbance heterogeneity model”; but until now the validity of these relationships has not been demonstrated for herbaceous species. By the demonstration of this effect between herbaceous species we can better forecast the responses of grasslands to changes in management

Platelet-derived extracellular vesicles may contribute to the hypercoagulable state in preeclampsia

It has previously been shown that preeclampsia is associated with disturbed hemostasis and that extracellular vesicles (EVs) play important role in the regulation of hemostatic homeostasis. Thus, we hypothesized that the altered procoagulant characteristics of circulating platelet-derived EVs may contribute to the disturbed hemostasis in preeclampsia. Using multicolor flow cytometry, we have analyzed both tissue factor expressing procoagulant EVs and platelet-derived EV subpopulations derived from resting and activated thrombocytes by examining them in plasma samples of preeclamptic patients and pregnancy-matched healthy individuals. Compared to pregnancy-matched healthy individuals in preeclamptic patients a significantly (p \u3c 0.05) higher ratio of Annexin-V positive activated platelets and a higher number of CD142+ tissue factor bearing procoagulant EVs were found, whereas the absolute amount of circulating CD41a+ platelet-derived EVs and CD62P+/CD41a+ EVs produced by activated thrombocytes was significantly lower in the plasma of preeclamptic women. In the plasma samples, there was no significant difference in the amount of CD63+ platelet-derived EVs. We propose that increased platelet activation and tissue factor expression of platelet derived extracellular vesicles may contribute to the hypercoagulable state observed in preeclampsia

Location and type of isocitrate dehydrogenase mutations influence clinical characteristics and disease outcome of acute myeloid leukemia

Background: Mutations of isocitrate dehydrogenase 1 and 2 are novel common genetic alterations identified in acute myeloid leukemia. Aims: To investigate the frequency, clinical associations and prognostic effect of isocitrate dehydrogenase 1 and 2 mutations together, followed by a detailed investigation of particular mutations. Methods: A consecutive cohort of 376 patients diagnosed with acute myeloid leukemia were enrolled to compare clinical characteristics. Prognostic impact was analyzed for 314 patients younger than 60 years treated with curative intention. Isocitrate dehydrogenase 1 and 2 mutations were screened using allele-specific PCR and high resolution melting, followed by a confirmatory sequencing. Results: Isocitrate dehydrogenase (IDH) 1 and 2 mutations were mutually exclusive, detected in 8.5% and 7.5% of the cases respectively. Presence of mutations was associated with older age (p=0.001), higher platelet count (p=0.001), intermediate risk karyotype (p<0.0001), nucleophosmin1 mutation (p=0.022), and with lower mRNA expression level of ABCG2 gene (p=0.006), as compared to mutation negative cases. Remission, relapse rates and overall survival were not different in IDH-mutation positive patients. Interestingly, particular mutations differred in association with nucleophosmin1 mutation: co-occurrence was observed in 14.3% of R132C vs. 70% of R132H carriers (p=0.02); and in 47.4% of R140Q vs. 0% R172K carriers (p=0.02) of IDH1 and IDH2 genes, respectively. R132H negatively influenced overall survival compared to isocitrate dehidrogenase 1 and 2 negative (p=0.02) or to R132C (p=0.019) patients. Conclusions: IDH mutations are frequent recurrent mutations in acute myeloid leukemia. Although a general common pathogenetic role is proposed, our results indicate that differences in clinical characteristics and treatment outcome may exist among disctinct mutations of both genes