Ionizing radiation is known to cause DNA damage, yet the mechanisms underlying potential transgenerational effects of exposure have been scarcely studied. Previously, we observed effects in offspring of zebrafish exposed to gamma radiation during gametogenesis. Here, we hypothesize that these effects are accompanied by changes of DNA methylation possibly inherited by subsequent generations. We assessed DNA methylation in F1 embryos (5.5 hours post fertilization) with whole genome bisulfite sequencing following parental exposure to 8.7 mGy/h for 27 days and found 5658 differentially methylated regions (DMRs). DMRs were predominantly located at known regulatory regions, such as gene promoters and enhancers. Pathway analysis indicated the involvement of DMRs related to similar pathways found with gene expression analysis, such as development, apoptosis and cancers, which could be linked to previous observed developmental defects and genomic instability in the offspring. Follow up of 19 F1 DMRs in F2 and F3 embryos revealed persistent effects up to the F3 generation at 5 regions. These results indicate that ionizing radiation related effects in offspring can be linked to DNA methylation changes that partly can persist over generations. Monitoring DNA methylation could serve as a biomarker to provide an indication of ancestral exposures to ionizing radiation.

Mixed connective tissue disease (MCTD) is a complex overlap disease with features of different autoimmune connective tissue diseases (CTDs) namely systemic sclerosis, poly/dermatomyositis and systemic lupus erythematous in patients with antibodies targeting the U1 small nuclear ribonucleoprotein particle. In this narrative review, we summarise the results of a systematic literature research which was performed as part of the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases project, aimed at evaluating existing clinical practice guidelines (CPGs) or recommendations. Since no specific CPGs on MCTD were found, other CPGs developed for other CTDs were taken into consideration in order to discuss what can be applied to MCTD even if designed for other diseases. Three major objectives were proposed for the future development of CPGs: MCTD diagnosis (diagnostic criteria), MCTD initial and follow-up evaluations, MCTD treatment. Early diagnosis, epidemiological data, assessment of burden of disease and QOL aspects are among the unmet needs identified by patients.

BACKGROUND: There is a lack of data related to real life, long-term safety, tolerability and compliance of omalizumab treatment in asthma patients beyond 6 years. AIM: Study aimed to assess safety, tolerability, compliance and all reasons for treatment discontinuation during 10 years on omalizumab. SUBJECT AND METHODS: This is a retrospective, observational study of uncontrolled asthma patients receiving omalizumab for the last 10 years. All data were collected from patients’ files (demographics, adverse events, comorbidities, compliance index, reasons for discontinuation of omalizumab). Reactions to omalizumab were classified as local and systemic, and their severity as mild, moderate or severe. Reactions were either immediate (minutes to hours after drug administration) or delayed (after days). Compliance to omalizumab, defined as Compliance index (CI), was calculated by comparing milligrams of given to milligrams of prescribed dose/ per year. RESULTS: Out of 35 patients receiving omalizumab, 15 drop out at different time points mostly due to treatment efficacy or appearance of new comorbidities. Patients who continue for the next ten years had mild to moderate adverse events related to omalizumab. There was no increased risk of severe adverse events during 10 years on omalizumab. Patient’s treatment tolerability, despite mild to moderate adverse events, is in favour of compliance. CONCLUSION: Compliance with omalizumab mildly decreased over 10 years but was not affected by severe adverse events of treatment or new comorbidities. Although, omalizumab is safe medicine appearance of new comorbidities has to be closely followed up.

The aim of this paper is the analysis of the importance of the beverages sector and concrete trade facilitation measures for CEFTA 2006 economies, in general and for their intra-regional trade, in particular. The paper analyses both trade in beverages of CEFTA 2006 economies and heterogeneous group of barriers that exporters and importers are faced with at the CEFTA 2006 beverages market. Additionally, the paper points to possible solutions for elimination of those barriers through the implementation of selected trade facilitation measures. As the most of problems are related to the trade facilitation and marked as problems that could be easily removed, the most recommendations are based on the WTO Trade Facilitation Agreement measures.

The aim of the research is to address the challenges that may be a constraint on economic growth and development. In the research, we used the relevant literature and acts that were in front of the delegates at the National Assembly of Republic of Srpska. The research question is: "What are the main characteristics of the Republic of Srpska's debt?" In line with this, the methods employed in this paper are the analysis and synthesis of previous researchs, theoretical findings and publicly accessible documents pertaining to the debt of Republic of Srpska, and an overview of the case studies.  The contribution of the paper is reflected in the explained wideness and the possibilities of using different sources of money, and the limits on which the debts can be used in order to achieve sustainability tasks. We have concluded that this year, the Republic of Srpska bill has reached the largest amount of debt – KM 858 million (755 million principal and 103 million interest). In line with the presented evidence, priority should be given to projects that would be financed by advantageous credit arrangements and to rationalize public spending. Despite the usual opinion, we have proven that the debt of the Republic of Srpska is sustainable - the average interest rate is lower than the GDP growth rate and that, although unpopular, the currency board system corresponds to the position of Republic of Srpska. However, we have pointed out the danger of stereotype that the public debt of less than 60% necessarily indicates that the country is in a good position.

Background To date there is scarce published evidence reporting the dual blood supply reaching anterior papillary muscle (APM), which descends from both major coronary arteries. Such a vascular configuration can prevent the dysfunction of right ventricular entire valvular system in case of the occlusion of proximal part of either right coronary artery (RCA) or left coronary artery (LCA). The aim of our study was to determine the vascular pattern of APM blood supply which originates from two main coronary arteries, in the context of the APM and septomarginal trabecula (SMT) topography. Methods The study was carried out using tissue obtained from 36 human hearts. The material was divided into four morphological types of SMT/APM arrangement. Vascularization and blood supply pattern of papillary muscle was investigated following the analysis of multiple tissue cross sections. The origin of APM arterial supply was traced back to both main coronary arteries. Cross-sectional area of the arteries was estimated at the base of APM and compared within mixed male-female population, aged 18–76. Results We noted that as much as 78% of entire APM material had a blood supply vasculature originating from both LCA and RCA branches. In contrast, 22% of cases APM was supplied by a single coronary artery, while in each case it proved to be LCA. We have never found APM arterial supply provided exclusively by RCA. In case of double AMP blood supply an average of total cross-section area of the arteries branching from LCA, was noted to be in excess of two and a half times bigger in type III and more than two times bigger in type IV, as compared with the arteries originating from RCA. Conclusions Our research confirm the possibility of double blood supply which vascularizes APM, but the finding does not necessarily apply in all cases. However, APM seems to be predominantly vascularized by arteries deriving from LCA, regardless of their morphological type.