The Role of miR-218-5p and TGF-B Signaling in Human Placenta from Normal and Comprised Pregnancies

Placenta is critical during pregnancy, forming the interface between mother and fetus. A key process in placental development is the differentiation and invasion of extravillous trophoblast cells (EVT). While some EVT invade the uterine interstitial space, a subset upregulates endovascular genes forming the endovascular EVT (enEVT) that invade decidual vessels. EnEVT are critical mediators in spiral artery remodeling (SAR), which is essential for proper placentation. Preeclampsia (PE) is a serious hypertensive disorder that can manifest during pregnancy. The cause of PE is unclear; however shallow EVT invasion, inadequate enEVT differentiation and SAR play crucial roles. The transforming growth factor- (TGF-) family is known to regulate placentation and has been implicated in the pathogenesis of PE. Specifically, TGF-s and Nodal are upregulated in PE placenta and they exert potent inhibitory effects on EVT invasion. MicroRNAs (miRNA) are small non-coding RNAs that regulate most physiological processes and are dysregulated in PE. In this study, we investigated the role of miR-218-5p in modulating TGF- signaling and placental development and their contribution to the pathogenesis of PE. The models used in our study included a human trophoblast cell line (HTR8/SVneo), first trimester placenta and decidua tissues, and clinical samples. Our findings indicate that the expression of miR-218-5p was downregulated in PE and upregulated during second trimester in healthy tissues. Overexpression of miR-218-5p promoted trophoblast migration and invasion. Furthermore, miR-218-5p upregulated key genes involved in enEVT differentiation and accelerated SAR in vitro. Using a TGF- signaling reporter, we found that basal and TGF--induced transcriptional activities were strongly inhibited by mir-218-1. TGF-2, Smad2, and Smad3 are predicted miR-218-5p targets, and their expression was inhibited by miR-218-5p. Both TGF-2 and Smad2 were able to partly rescue the miR-218-5p phenotype. Interestingly, knockdown of Smad2 promoted, while knockdown of Smad3 inhibited, invasion and enEVT differentiation, suggesting they play differential roles in placentation. Additionally, the level of pSmad3 is strikingly downregulated in PE placentas. In conclusion, our study demonstrates that TGF- signaling in the maternal-fetal interface is modulated by miR-218-5p and disruption of the balance between miR-218-5p and TGF- signaling may lead to abnormal placental development and pregnancy complications

Organization and Application of Information Technologies in Enterprises of Herzegovina Region

Rapid development of information technologies has had a big influence on global economy and has activated the series of changes such as: globalization, liberalization, concurrency growth, market expansion, availability of market information to all segments etc. Also, the significance of the Information itself has become larger since information technologies are making the process of gathering, processing, storing and distributing of data much easier with the primary goal of possessing the right information at the right time and at the right place in the organization with minimization of costs. The achievement of this goal is leading to improvement in all segments of business activity such as: research and development of new products, process of supply, supply management, accounting and finance, marketing, sales, control, communication and decision making. Application of information technologies in the modern business does not only include buyingand owning PCs in the company, but also a presence of high quality organization and utilization of information technologies which is a guarantee for successful and competitive existence in the market. What kind of information system should be implemented is dependant on the company size, amount of information and data it operates with, the type of business, future plans etc. The objective of this research is to get the picture of level of enterprise informatization in Herzegovina with respect to amount and manner of information technology utilization. From these goals, the following hypotheses were set: H1 – information technologies are insufficiently used and are not appropriately organized in the companies of Herzegovina region H2 – there are substantial differences in utilization and organization of information technologies in the enterprises of Herzegovina region regarding their size This paper will present the research based on the original questionnaire from the project named "Research and need analysis for training and consultative services for small and medium enterprises in the Herzegovina region" which was carried out by the authors for the Herzegovina regional development agency. The research was conducted in the end of year 2008 and in the beginning of 2009 and it comprised 105 enterprises from the Herzegovina region which spans over Federation of Bosnia and Herzegovina and Republic of Srpska. The size of the enterprise (micro, small, medium and large) was defined through a two-dimensional criteria including two variables: number of employees and total income. The research is expected to confirm the hypothesis and create the foundation for undertaking the appropriate actions in order to change the current, unsatisfying situation.Information technologies, organization, enterprise, Herzegovina

Lifetime and past-year prevalence of children’s exposure to violence in 9 Balkan countries: the BECAN study

Background Children’s exposure to violence is a major public health issue. The Balkan epidemiological study on Child Abuse and Neglect project aimed to collect internationally comparable data on violence exposures in childhood. Methods A three stage stratified random sample of 42,194 school-attending children (response rate: 66.7%) in three grades (aged 11, 13 and 16 years) was drawn from schools in Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Former Yugoslavian Republic of Macedonia (FYROM), Greece, Romania, Serbia and Turkey. Children completed the ICAST-C questionnaire, which measures children’s exposure to violence by any perpetrator. Results Exposure rates for psychological violence were between 64.6% (FYROM) and 83.2% (Greece) for lifetime and 59.62% (Serbia) and 70.0% (Greece) for past-year prevalence. Physical violence exposure varied between 50.6% (FYROM) and 76.3% (Greece) for lifetime and 42.5% (FYROM) and 51.0% (Bosnia) for past-year prevalence. Sexual violence figures were highest for lifetime prevalence in Bosnia (18.6%) and lowest in FYROM (7.6%). Lifetime contact sexual violence was highest in Bosnia (9.8%) and lowest in Romania (3.6%). Past-year sexual violence and contact sexual violence prevalence was lowest in Romania (5.0 and 2.1%) and highest in Bosnia (13.6 and 7.7% respectively). Self-reported neglect was highest for both past-year and lifetime prevalence in Bosnia (48.0 and 20.3%) and lowest in Romania (22.6 and 16.7%). Experiences of positive parental practices were reported by most participating children in all countries. Conclusions Where significant differences in violence exposure by sex were observed, males reported higher exposure to past-year and lifetime sexual violence and females higher exposure to neglect. Children in Balkan countries experience a high burden of violence victimization and national-level programming and child protection policy making is urgently needed to address this

Executive Functions Rating Scale and Neurobiochemical Profile in HIV-Positive Individuals

The set of complex cognitive processes, that are necessary for the cognitive control of behavior, known as executive functions (EF), are traditionally associated with the prefrontal cortex and commonly assessed with laboratory based tests and conventional neuroimaging. In an effort to produce a more complete and ecologically valid understanding of executive functioning, the rating scales have been developed in order to assess the behavioral aspects of EF within an everyday real-world context. The main objective of this study was to examine the relationship between behavioral aspects of EF measured by rating scale and neurometabolic profile in neurologically asymptomatic HIV-positive individuals under cART, measured using multi-voxel magnetic resonance spectroscopy (mvMRS). The sample comprised 39 HIV-positive adult male participants, stable on cART and 39 healthy HIV-negative volunteers. Both groups completed the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). HIV-positive group additionally underwent long-echo three-dimensional mvMRS to determine neurobiochemical profile in the anterior cingulate gyrus (ACG) of both hemispheres. Three dominant neurometabolites were detected: N-acetyl aspartate (NAA), the neuronal marker; choline (Cho), the marker of membrane metabolism and gliosis and creatine (Cr), the reference marker. Ratios of NAA/Cr and Cho/Cr were analyzed. The initially detected significant correlations between age, current CD4, BRIEF-A subscales Inhibit, Shift, Emotional Control, Plan/Organize, Self Monitoring and ratios of NAA/Cr and Cho/Cr in the dorsal and ventral part of the ACG, were lost after the introduction of Bonferroni corrections. Also, there were no significant differences between HIV–positive and HIV–negative group on any of BRIEF-A subscales. Such results possibly imply that stable cART regimen contributes to preservation of behavioral aspects of EF in asymptomatic HIV-positive individuals. Even though a subtle deficit in some aspects of EF might exist, it would not be manifest if behavioral aspect was assessed using EF rating scale. Further explanation might be that expected HIV-related changes in neurometabolic profile of the ACG under cART are not reflected in those behavioral aspects that are measurable by EF rating scale

Effects of Nonsurgical Periodontal Therapy on Salivary 8-Hydroxy-Deoxyguanosine Levels and Glycemic Control in Diabetes Mellitus Type 2 Patients

Diabetes and periodontitis are complex chronic diseases that are potentially interrelated, as well as associated with oxidative stress. Thus, the aim of the present study was to evaluate the influence of nonsurgical periodontal treatment on salivary 8-hydroxy-deoxyguanosine (8-OHdG) levels and glycemic control in patients suffering from both diabetes mellitus type 2 (DM2) and periodontitis. The study sample included 53 DM2 patients, while 31 systemically healthy patients served as controls. Participants in both groups suffered from periodontitis of comparable severity. Periodontal clinical parameters, namely plaque index (PI), gingival index (GI), papilla bleeding index (PBI), probing pocket depth (PPD), and clinical attachment level (CAL) were recorded, along with salivary 8-OHdG levels and glycated hemoglobin (HbA1c). Levels of 8-OHdG were analyzed by ELISA. All aforementioned parameters were evaluated prior to commencing the study and at 90-day follow-up upon nonsurgical periodontal therapy completion. At baseline, salivary levels of 8-OHdG in DM2 patients were significantly higher (1.17 ng/mL) than those measured for the control group (0.75 ng/mL) and showed significant positive correlation with GI and PPD (p < 0.05). Three months after nonsurgical periodontal therapy, the salivary 8-OHdG levels were significantly reduced in DM2 patients (p < 0.05). Analysis results also revealed statistically significant changes in all measured clinical parameters between baseline and three-month follow-up in both groups (p < 0.05). Upon treatment completion, a decline in the HbA1c level was noted in DM group, but it did not reach statistical significance (p > 0.05). It can be concluded that DM2 patients benefit from non-surgical periodontal therapy, as indicated by a marked reduction in their salivary 8-OHdG level and a modest improvement in glycemic control. Short-term clinical benefits noted in the DM group were similar to those observed in the non-diabetic periodontal patients