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Providing a good quality in higher education should be the result of the interaction between the academic team, the students and the institutional learning environment. The quality is guaranteed by the learning environment in which the content of the programs and training opportunities is appropriate for the particular purpose. Aim: To study the organization, quality, consistency and satisfaction in practical training. Materials and Methods: This article presents and analyzes the results of a survey by medical graduates about their assessment of the organization and quality of training during the undergraduate internship. Results: The results show that the practical training of medical graduates is generally at a very high level, according to the indicators, examined in our study. Conclusion: More efforts in improving quality of education are welcome.

Aim To examine the success rate and factors affecting the effect of conservative treatment for congenital nasolacrimal duct obstruction (CNLDO) in children. Methodology A prospective study was made on 167 eyes of 131 patients with clinical signs of CNLDO. All of them were initially treated nonsurgically with Crigler massage. The curative effect of this management was evaluated on the basis of no history of watery eyes, negative regurgitation test, and dye disappearance test 0 or 1 grade. Exploratory analyses assessed whether baseline characteristics including age, gender and laterality were associated with the probability of CNLDO resolving without surgery. If the nonsurgical treatment failed, probing was done in the Eye Clinic in Pleven. Results The conservative treatment for CNLDO with Crigler massage was successful in the majority of treated cases – in 115 out of 167 eyes with CNLDO (68,9%). The remaining 52 (31,1%) eyes were probed. Age (p = 0,001) and laterality (p = 0,001) were found to be associated with resolution of the clinical signs. Conclusions Nonsurgical management for CNLDO was successful initial treatment in patients with this pathology. The Crigler massage was more effective in children up to 12 months of age with unilateral obstruction.

Aim: The objective of the present study was to make a complex evaluation of behaviour, lipid metabolism, inflammation, and bone turnover in an ovariectomized rat model used to simulate postmenopausal clinical findings.Materials and methods: Female Wistar rats were divided into 2 groups of 16 animals each: sham operated (SO) animals and ovariectomized (OVX) animals. Three months after the operation, a battery of behavioural tests was performed including an open field test (OFT), elevated pus-maze test (EPM), the social interaction test (SIT), the forced swim test (FST), and a hot plate test (HPT). At termination of experiment, weight gain and fat deposits (total and retroperitoneal) were measured. Serum concentrations of blood lipids were determined. Tumor necrosis factor alpha (TNF-alpha) and alkaline phosphatase (ALP) serum concentrations were used for evaluation of the inflammation and bone turnover, respectively. Femur bone mineral density (BMD) was evaluated using dual energy X-ray absorptiometry.Results: OVX rats did not demonstrate any significant behavioural changes in OFT and EPM tests but showed a decreased interaction time in SIT and an increased immobility time in FST test which indicated anxiety and depression. The OVX rats had a significantly lower pain sensitivity threshold. They had greater weight gain, increased total and retroperitoneal fat deposits, as well as elevated total fat/body weight and retroperitoneal fat/body weight ratios. Blood cholesterol, ALP and TNF-alpha of the OVX group were also significantly higher. Femur BMD of OVX rats was slightly but not significantly reduced.Conclusions: Estrogen deficiency in OVX rats caused depression, anxiety, hyperalgesia, obesity, dyslipidemia, and inflammationbefore the reduction in bone mineral density was prominent.

All technologies and materials nowadays aim to ensure the elimination of pain, providing greater comfort and satisfaction for the patient. Research on patients' perceptions of the technologies used is gaining in popularity. The aim of this article is to study and compare the opinions of patients who have sought dental care to treat a defect in the dentition with restorations made using a conventional and digital impression. Materials and methods: The survey involved 116 patients who sought dental care in two private practices in Varna, Bulgaria. To achieve the goal of the survey, special questionnaires have been developed, in which there are two types of questions: with only one or more than one possible answer. Results: Most of the participants (81%) report that they have at least one extracted tooth, which is not a third molar (wisdom tooth). Patients over the age of 40 are more likely to have a missing tooth. Slightly more than 1/3 of the patients or 35% indicated impaired masticatory and aesthetic function. Most of the patients prefer a prosthetic treatment with a fixed restoration. On 76,7 % of the patients a conventional impression was taken during dental treatment and only 12 % report that they undergo a treatment with digital impressions. Conclusion: Our results show that males are at a higher risk for premature loss of permanent teeth than females. (OR=2.17 (0.830-5.654); p

With the advancement of medicine and the development of new technologies, more and more manufacturing companies consult dental specialists about their opinion on certain techniques, materials and devices in order to improve and refine them. The purpose of this article is to compare and study the opinion of dentists and dental technicians on the treatment with fixed restorations of zirconium dioxide, made using a conventional and digital impression technique. Materials and methods: Using anonymous questionnaires of 20 questions, the opinion of 72 dentists and 53 dental technicians was documented regarding the clinical and laboratory wrokflow protocol and the final result in the treatment with fixed partial dentures made of zirconium dioxide. Results: The majority of dentists treat a distally limited defect with a small number of mising teeth with a fixed partial dentures (86.1%). The most commonly used are porcelain-fused to metal with a non-precious alloy framework (83% for dental technicians and 93.1% of dentists, respectively), followed by zirconium dioxide structures (39.60% for dental technicians and 37.50% for dentists, respectively). Conclusion: The main way in which dentists and dental technicians treat distally limited defects of the dentition is through fixed porcelain-fused to metal restorations. Most dental professionals use a two-stage two-layer impression technique with addition silicones and standard metal impression trays.

In the last few decades, the problem with falsified medicine became a global threat that accounts for millions of human lives and billions of financial loses for the national health authorities and pharmaceutical industry. Different measures were developed to fight their uncontrolled spread but had only limited success. The resolution that united the pharmaceutical supply chain actors worldwide is the introduction of track-and-trace systems, based on product serialization and verification. The European Union also adopted this solution, and its official operation began in 2019. Each Member State has specifics that have to be accounted for in the national transposition process and should influence the system design and functionalities. In Bulgaria, the responsible authorities seriously delayed to adopt an adequate legal and regulatory framework to support its smooth operation. This created many problems for some of the key supply chain participants – the wholesalers. Since the European system is not a full track-and-trace solution, their role in the verification process is limited and left to the national authorities to decide how to regulate it. At present, more than one year after the launch of the system, the national bylaws that should regulate their activities with reference to the European policy are still not enforced. The wholesalers are left to align their operations in a regulatory vacuum that may compromise the effectiveness of the policy and lead to sanctions for noncompliance.

The globalization of trade and internet access significantly increased the health risks associated with falsified medicines. International organizations, pharmaceutical companies and national governments developed a wide variety of measures to combat their pervasive penetration into the legal supply chains. However, the lack of harmonization, broad acceptance and legally bound enforcement obstructed their endeavours. The unsatisfying outcomes resulted in enhanced supranational cooperation focused on strengthening the pharmaceutical regulatory frameworks and the improvement of patient protection. In 2011 the European Union joined the global fight with the adoption of Directive 2011/62/EU that became known as the Falsified Medicine Directive. It is legally binding for Member States and amends the fundamental for the pharmaceutical sector Directive 2001/83/EC. The objective of the present paper is to verify if it represents a comprehensive tool for effective prevention of the access of falsified medicines in the European legal pharmaceutical supply chains. The results revealed that although it is rather detailed, there are areas that could be further developed and improved when compared to analogical policies and initiatives.

Aims: We aimed to evaluate the prevalence of irritable bowel syndrome (IBS), functional dyspepsia (FD), and their overlap syndrome (OS) in the Bulgarian population and to assess the risk factors associated with these disorders. Methods: We sent an internet-based survey to Bulgarian adults. The survey collected data on socio- demographic, behavioral and lifestyle characteristics, and diagnostic questions following the Rome IV criteria to assess IBS, FD and their overlap occurrence. Results: Data was collected from 1,896 individuals (mean age = 35.5 years, 18-65, SD=11.7), 73.1% females. The prevalence of IBS was 20% (14% were with predominant constipation, 32% with predominant diarrhea, 52% had IBS with mixed bowel habits, and 2% unclassified IBS). Gender (p=0.005), age (p

The orphan drugs development is related to the progress of personalized medicine. The relationship between them is based on a treatment tailored to personalized patient needs. Personalized medicine is defined as “providing the right patient with the right drug, at the right dose and at the right time”, while the orphan drug is defined as “intended for the treatment, prevention or diagnosis of a rare disease or condition, which is one that affects less than 200,000 persons in the United States” and no more than 10,000 people for the European Union. The main goal of the article is to study the approved orphan drugs in Bulgaria, determining how many of them are reimbursed by the NHIF and are cost-effective

Foodborne and waterborne viruses are a major cause of human morbidity. Of them, noroviruses are recognised as the leading causative agents of sporadic infections and epidemic outbreaks of acute gastroenteritis in humans. Contaminated food products and water are the main source of infection with noroviruses. The infection of bivalve molluscs with human pathogenic viruses occurs by faecal contamination in the production coastal waters. In this study, 47 samples of live bivalve molluscs, including 15 samples of cultivated mussels (Mytilus galloprovincialis) and 32 samples of wild mussels (Tapes decussatus), collected from the Bulgarian and Mediterranean coasts, respectively, were submitted to RT-real-time TaqMan PCR to detect the presence of noroviruses genotype GI and GII. Norovirus genotype GII was found in 11 (23.4%) of all the samples tested. A single mollusc sample (2.1%) was positive for both norovirus genotypes. Our results demonstrated that shellfish intended for sale on the Bulgarian market might pose a potential risk for acquiring norovirus infection. Thus, food safety quality control of shellfish by optimised and standardised methods for detection of foodborne viruses, including noroviruses, should be urgently implemented in Bulgaria.

Summary The study aimed to identify the type of refraction in children with unilateral and bilateral congenital nasolacrimal duct obstruction (CNLDO) who underwent nasolacrimal duct probing. One hundred and twelve children aged 1.8 to 13 years, diagnosed with CNLDO, were included in a retrospective study. All the patients had their visual acuity examined, and their refractive status was evaluated. The refractive errors of both eyes were noted, followed by an appropriate management plan. Of the 112 children, 79 (70.5%) had a unilateral obstruction, and 33 (29.5%) had bilateral obstruction. Nine children (11.4%) in the former group and six children (18.2%) in the latter group were with visual acuity 0.05) between refraction of the two eyes in the evaluated children were found. Amblyopia risk factors were identified in 9 of the patients (8.0%). CNLDO did not adversely affect the refractive status. However, amblyogenic risk factors were found more often in our patients, as compared to general populations. Therefore, a detailed evaluation should be performed to find out these risk factors.

Depression and anxiety are prevalent chronic psychiatric disorders affecting many people worldwide. Over the past decades, much attention has been drawn to herbal psychopharmacology, offering fewer adverse reactions. The main bioactive compounds in Chaenomeles maulei fruits are polyphenols known for their behavioral effects. The objective of the present study was to assess Chaenomeles maulei fruit juice (CMFJ) effects in tests for anxiety and depression. The animals used were 32 male healthy Wistar rats treated orally with CMFJ for 16 days. They were divided in four groups of 8 animals. The control group received distilled water and the rest of the groups were treated with CMFJ at 2.5, 5 and 10 ml/kg doses. We assessed the social interaction time as a measure of anxiety and the immobility time in the forced swim test as a measure of behavioral despair. In the social interaction test, the 14 days administration of CMFJ did not produce any significant changes in the time spent in social interaction. After 16 days of administration all doses of CMFJ significantly decreased the immobility time of the rats (p < 0.05) in comparison to the control group. These results allow making the conclusion that CMFJ lacked anxiolytic activity, but showed an antidepressant-like effect.

Purpose: To discuss the various epidemiological aspects and the impact risk factors for developing CNLDO in children. Material/Methods: An analytical observational case-control study. Оne hundred and thirteen children diagnosed and probed for CNLDO in Eye clinic-Pleven were included in a case group. A control group consisted of 121 children without CNLDO. All of the parents answered questions from specially designed questionnaires related to the pregnancy of the mother, antenatal risk factors and child’s health in the neonatal period. Results: The demographic profile of the evaluated children in the case group was: 49.6% males and 50.4% females; 33% cases were with affected right eye, 37% left eye, and 30% individuals with bilateral CNLDO after birth. Median gestational age of the children with CNLDO was 40.0. Risk factors for CNLDO development are antibiotics intake and consuming alcohol during the pregnancy. Conclusion: Congenital nasolacrimal duct obstruction affects full-term born children. Detection of the risk factors for developing CNLDO will improve methods for the prevention of this disease.

The BS-MFC (Black Sea Monitoring and Forecasting Centre) since 2016 is guaranteeing production and delivery of high quality ocean analysis, forecast and reanalysis fields for essential variables, biogeochemical quantities and waves in the Black Sea region within the Copernicus Marine Service. A reliable and robust service infrastructure serves both the production systems and data delivery, through ad hoc technical interfaces, for an efficient update of the catalogue, which includes 22 datasets for physical variables, 22 for biogeochemical variables and 4 for waves. Additionally, a Local Service Desk is in charge for ensuring connections among BS-MFC, CMEMS and Users with the scope to support end-users in using BS-MFC data for downstream applications from the technical and scientific perspectives. The production centres are the core of the BS-MFC: Physics, Biogeochemistry and Waves units implemented, over the Copernicus 2 Programme, state-of-the-art and advanced numerical approaches to improve the quality of the near real time and multi year products. In the 2020, in particular, the BS-Physics team proposed a new reanalysis product, based on new version of the hydrodynamical core model, based on NEMO v3.6, with assimilation of CMEMS observations (e.g. insitu temperature and salinity profiles, including also historical dataset provided by SeaDataNet, and sea level anomaly satellite data) and forced by ECMWF ERA5. The BS-Physics team is working also on preparing the new version of the near real time system, that will provide spatial high resolution analysis and forecast products, using a new version based on NEMO v4.0, online coupled to data assimilation scheme, with optimal interface with the Mediterranean Sea. BS-Biogeochemistry team updated the overall catalogue, with new near real time system, based on NEMO v3.6 online coupled to BAHMBI model, with new carbonate model, able to assimilate new chlorophyll satellite data provided by the CMEMS OC TAC; regarding multi year product, the BS-Biogeochemistry team delivered new datasets, generated by the new NEMO-BAHMBI coupled system forced by ECMWF ERA5 – totally aligned with the near real time system, without data assimilation – for reconstructing the past biogeochemical sea state in the Black Sea. BS-Waves team updated the overall catalogue as well, with new near real time system based on state-of-the-art WAM Cycle 6.0, one-way coupled with hourly currents fields provided by the BS-Physics near real time system; a new reanalysis, from 1979 to 2019, has been also delivered, based on same core model as the near real time system, forced by ECMWF ERA5 atmospheric forcing, and able to assimilate the significant wave height provided by CMEMS SL TAC. Systems are monitored through a product quality dashboard, based on standards inherited from GODAE/Oceanpredict and MERSEA/MyOcean (which includes CLASS 1, 2 and 4 metrics).

Using RF magnetron sputtering, we deposited Bi12TiO20 (BTO) thin films on various substrates (glass, quartz, stainless steel (SS304), (001) and (111) Si and sital-ceramics, Al and Cu foils). The films had a constant thickness of 1.3 μm. The as-deposited films were studied by Raman spectroscopy, scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX), as well as by grazing incidence X-ray diffractometry (GIXRD). The GIXRD results reveal that the films are amorphous, while the Bi/Ti ratio varies between 9.5/1 and 11.8/1, as shown by the energy dispersive X-ray analysis (EDX). Further, the films deposited on glass and SS304 substrates were modified by laser irradiation (CuBr laser with a wavelength λ = 511 nm) to obtain an ordered cubic phase. The films deposited on quartz and on (001) and (111) Si substrates were thermally annealed at about 510 oC for three hours in ambient atmosphere. The modified films were characterized by Raman spectroscopy, scanning electron microscopy (SEM), EDX and X-ray diffractometry.

The ultimate goal of modern operational oceanography are end user oriented products with high scientific quality. Beneficiaries are the governmental services, coast and offshore based enterprises and research institutions that make use of the products generated by operational oceanography. Direct users are coastal managers, shipping, search and rescue, oil spill combat, offshore industry, ports, fishing, tourism, and recreation industry. Indirect beneficiaries, through climate forecasting based on ocean observations, are food, energy, water and medical suppliers. Availability of updated information on the actual state as well as forecast of marine environment is essential for the success and safety of maritime operations in the offshore industry. Various systems for the collection and presentation of marine data for the needs of different users have been developed and put in operation in the Black Sea. The systems are located both along the coast and in the open sea and the information they provide is used by both the maritime industry and the widest range of users. The Black Sea Monitoring and Forecasting Center in the frame of the Copernicus Marine Service is providing regular and systematic information about the physical state of the ocean, marine ecosystem and wave conditions in the Black Sea area, assimilating observations, keeping efficient operations, advanced technology and high quality modeling products. Combining and optimizing in situ, remote sensing, modeling and forecasting into a Black Sea observing system is a task that has to be solved, and that will allow to get a more complete and comprehensive picture of the state of the marine environment as well as to forecast future changes of physical and biogeochemical state of the Black Sea and the Black Sea ecosystem.

Background No trials have compared cabozantinib and regorafenib for the second-line treatment of advanced hepatocellular carcinoma (HCC). Objectives Conduct a matching-adjusted indirect comparison (MAIC) of the efficacy and safety of second-line cabozantinib and regorafenib in patients with advanced HCC and disease progression after prior sorafenib. Methods The CELESTIAL and RESORCE trials were used for indirect comparison of second-line cabozantinib and regorafenib in advanced HCC. Population-level data were available for RESORCE, individual patient data (IPD) for CELESTIAL. To align with RESORCE, the CELESTIAL population was limited to patients who received first-line sorafenib only. To minimize potential effect-modifying population differences, the CELESTIAL IPD were weighted to balance the distribution of clinically relevant baseline characteristics with those of RESORCE. Overall survival (OS) and progression-free survival (PFS) were evaluated for the matching-adjusted second-line CELESTIAL population and compared with those for RESORCE using weighted Kaplan-Meier curves and parametric modeling. Rates of grade 3/4 treatment-emergent adverse events (TEAEs) affecting > 5% of patients in any study arm were compared. Results In the matching-adjusted second-line populations (CELESTIAL, effective sample size = 266; RESORCE, n = 573), median (95% confidence interval) OS was similar for cabozantinib and regorafenib (11.4 [8.9–17.0] versus 10.6 [9.1–12.1] months; p = 0.3474, log-rank test). Median PFS was longer for cabozantinib than regorafenib (5.6 [4.9–7.3] versus 3.1 [2.8–4.2] months; p = 0.0005, log-rank test). There was a trend for lower rates of some grade 3/4 TEAEs with regorafenib than with cabozantinib, which may reflect the exclusion of sorafenib-intolerant patients from RESORCE but not from CELESTIAL, a difference that the MAIC methods could not remove. Only diarrhea rates were statistically significantly lower for regorafenib (p ≤ 0.001). Conclusions Cabozantinib may achieve similar OS and prolonged PFS compared with regorafenib in patients with progressive advanced HCC after prior sorafenib. Electronic Supplementary Material The online version of this article (10.1007/s12325-020-01378-y) contains supplementary material, which is available to authorized users., Plain Language Summary Cabozantinib and regorafenib are treatments approved for some patients with advanced hepatocellular carcinoma (HCC), a type of liver cancer, after disease progression despite prior sorafenib treatment. Cabozantinib, regorafenib and sorafenib are tyrosine kinase inhibitors (TKIs), meaning that they slow cancer progression by targeting specific ways that tumors grow. Cabozantinib and regorafenib offer benefits to patients compared with placebo (i.e., no treatment) for those who have progressed despite sorafenib treatment. No clinical studies have compared cabozantinib and regorafenib directly. This study compared the efficacy and safety of cabozantinib and regorafenib using data from trials of each drug versus placebo: CELESTIAL for cabozantinib and RESORCE for regorafenib. These two trials were similar—both involved patients with progressive advanced HCC who had received previous cancer treatment. There were some important differences, but these were minimized using statistical methods (matching and adjustments/“weighting”) allowing outcomes to be meaningfully compared. One difference that could not be removed by the statistical methods was that patients who were intolerant to prior sorafenib were excluded from RESORCE but were eligible for the CELESTIAL trial. In the otherwise matched populations, treatment with cabozantinib was associated with similar overall survival and significantly longer progression-free survival than regorafenib. Rates of diarrhea were significantly lower for regorafenib than cabozantinib, suggesting that regorafenib may be better tolerated, but this may reflect the exclusion of sorafenib-intolerant patients from RESORCE. These findings cannot replace a head-to-head study, but may help in guiding decision-making between cabozantinib and regorafenib in patients with progressive advanced HCC after soraftenib treatment. Electronic Supplementary Material The online version of this article (10.1007/s12325-020-01378-y) contains supplementary material, which is available to authorized users.

It is estimated that up to 40% of all head and neck paragangliomas (HNPGL) have a hereditary background with the most common mutations being found in the succinate dehydrogenase (SDH) genes. SDHAF2 mutation leads to the rare paraganglioma syndrome 2. The authors present the case of a 15-year-old male patient with 2, non-secretory HNPGLs, presenting with left-sided, pulsatile tinnitus, and hearing loss. Imaging led to the suspicion of a jugulotympanic paraganglioma on the left, as well as a carotid body tumor on the right. After resection of the jugulotympanic tumor, histology confirmed the presence of a paraganglioma; immunohistochemistry furthermore suggested a loss of SDHB expression. Genetic testing revealed a rare germline, loss-of-function mutation in the SDHAF2 gene, previously described to cause hereditary paraganglioma syndrome 2. Twenty months after the first operation, the patient underwent a resection of the right carotid body paraganglioma. Plasma-free metanephrines/catecholamines always remained within the reference range; the patient is under regular follow-up, and his relatives will be screened. Our findings emphasize the relevance of genetic testing in patients with HNPGL, also with negative family history, especially when the patients present at a young age and with multiple lesions.

Summary Aronia melanocarpa fruit juice (AMFJ) has been intensively studied for effects on the central nervous system. The study aimed to investigate AMFJ for possible sedative-hypnotic effects in rats after acute and subchronic administration. Male Wistar rats were treated orally with three doses of AMFJ (2.5, 5.0 and 10.0 ml/kg) either once (acute treatment) or in 30 days (subchronic treatment). Control rats were similarly treated with distilled water. The tests were performed 1 hour after the last AMFJ administration. The possible sedative-hypnotic effects of the juice were investigated in the open field test (OFT) and thiopental-induced sleeping time test. Substances with sedative-hypnotic effects decrease locomotor activity in the OFT and prolong the time of thiopental-induced sleep. The results from the OFT showed that neither the acute, nor the subchronic treatment of rats with all AMFJ doses affected the horizontal and vertical locomotor activity significantly. The two patterns of administration of AMFJ (acute and subchronic) had no significant effect on the duration of thiopental-induced sleep. The lack of effect of AMFJ on locomotor activity and the lack of prolongation of thiopental-induced sleep showed that AMFJ did not display sedative-hypnotic effects in rats.

Summary Chaenomeles maulei is the name of the cultivar of Chaenomeles japonica, which was introduced in Europe. The present study aimed to investigate the chemical composition and the antioxidant activity of Chaenomeles maulei fruit juice (CMFJ). The ingredients of the juice sample were measured by spectrophotometric, high-performance liquid chromatography (HPLC) and gravimetric methods. The antioxidant activity was measured by the oxygen radical absorbance capacity (ORAC) and hydroxyl radical averting capacity (HORAC) assays. The results showed that CMFJ was extremely rich in polyphenolic substances, amongst which the highest was the concentration of procyanidin oligomers, followed by phenolic acids (vanillic > caffeic > chlorogenic > neochlorogenic > p-coumaric > ellagic > ferulic > 4-dihydroxy-benzoic) and flavonoids (epicatechin > catechin > quercetin-3-β-glucoside > quercetin > rutin > naringin > kaempferol > myricetin). The sour taste of the juice and its low pH were due to the high content of organic acids (malic > quinic > citric > shikimic > ascorbic > oxalic). The carbohydrates were presented by glucose > fructose > galactose > xylose > rhamnose > arabinose. The antioxidant activity measured by ORAC and HORAC was very high. It could be attributed to the high content of polyphenolics in the juice.

Trinitrobenzensulfonic acid (TNBS) is commonly used to induce an experimental inflammatory bowel disease (IBD) model. Oxidative stress and inflammation have been proposed as mechanisms underlying the pathophysiology of IBD. Aronia melanocarpa fruit juice (AMFJ) is extremely rich in polyphenolic substances, mainly proanthocyanidins, flavonoids and phenolic acids. The aim of this study was to evaluate the effect of AMFJ in a rat TNBSinduced colitis model and to compare the effect of the juice with that of sulfasalazine. Colitis was induced by TNBS in male Wistar rats. After the induction of colitis, AMFJ at three doses (2.5, 5 and 10 mL/kg) and sulfasalazine (400 mg/kg) were administered orally till the 14th experimental day. Severity of colitis was assessed by macroscopic and histopathological criteria. Oxidative stress was evaluated by the concentration of thiobarbituric acid reactive substances (TBARS). TNBS caused severe colonic damage. AMFJ dose-dependently ameliorated TNBS-induced colitis. It improved the macroscopic and microscopic signs of colitis, and prevented the increase of colonic TBARS concentrations. Regarding different indices, the effect of AMFJ was comparable or even higher than that of sulfasalazine. In conclusion, the ameliorative effects of AMFJ in the experimental TNBSinduced colitis might be the result of its potent antioxidant and antiinflammatory properties.

Introduction: The influence of mouth breathing on the development of the dentition and dento-facial deformities is a problem causes concerns among the medical specialists. Mouth breathing has a major impact on the development of the maxillo-facial region, occlusion and muscle tonus. Aim: The aim of this study is to assess the relationship between etiological factors, pathogenesis and disturbances in mastication in mouth breathing patients. Material and methods: For this article, data is obtained from 43 medical, literary sources. Results: Literature review demonstrated that mouth breathing habit affects mostly children aged 7 - 12 years. In the vast majority of studies, the authors established a relation between mouth breathing and the development of maxillo-facial region and occlusion. The malocclusions described include a distal occlusion, anterior open bite, increase overjet, posterior crossbite, crowding and average incisors inclination disturbances. These clinical conditions become more complicated in the late-mixed and permanent dentition if mouth breathing continues to persist. Conclusion: The habitual mouth breathing is a great medical problem nowadays. An increasing numbers of patients with this condition although the development of technology for early diagnostic is embarrassing. This condition is strongly related with different malocclusions such as anterior open bite, overjet, distal occlusion, underdeveloped and narrow upper jaw, increased anterior facial height.

Introduction: Bromonidine tartarate ophthalmic solution (CAS registry-number: 70359- 46-5) is a relatively selective alpha-2 adrenergic agonist, indicated for the lowering of intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Aim: The purpose of the present phase-1 clinical trial was to assess the pharmacodynamic equivalence of two ophtalmic solutions containing brimonidine tartarate 0,2% in healthy volunteers. Methods: The study was performed as a single center, randomized, single-dose, observer-blinded, single period trial in 36 healthy volunteers. Each volunteer received successively and in a random way a single dose of 1 drop of the test or the reference product in the conjunctival sac of the right and left eye, respectively. Measurement of intraocular pressure (IOP) of both eyes was performed at screening examination, pre-dose and 2 hours post dosing and at final examination by means of a Goldmann applanation tonometer. The primary target parameter for proving pharmacodynamic equivalence was defined as the absolute decrease in IOP 2 hours post dose. The 95% confidence interval was calculated for the difference (test-reference) of the primary target parameter and compared with the predefined equivalence range of ±1.5 mmHg. Results: A decrease in the IOP of 4.60±1.26 mmHg and 4.40±0.89 mmHg was observed after administration of the test and reference formulation, respectively. The mean difference was +0.197 mmHg with a 95% confidence interval between -0.275 and 0.670 mmHg and thus entirely within the predefined equivalence range. Both products showed a very good local safety profile and similar tolerability. Conclusion: Brimonidine Tartrate Ophthalmic Solution 0.2% was pharmacodynamically equivalent to the reference preparation (Alphagan®) with respect both to efficacy and safety.

Congenital lacrimal fistula is a developmental abnormality. This is a case of a patient with an external congenital lacrimal sac fistula. Surgical treatment was used to correct the condition. Immediate postoperative results were seen. To present a case of a patient with an external congenital lacrimal sac fistula, in which surgical treatment was applied and immediate postoperative results with a good outcome were seen. A 3-year-old boy with an external congenital lacrimal sac fistula presented to our clinic. The skin orifice was observed on the left eye in a typical place – located in the inferomedial aspect of the medial canthal angle. The patient was treated in the at the Eye clinic, at university hospital “Dr. Georgi Stranski” – Pleven, Bulgaria. He underwent a surgical procedure – simple fistula excision (closed fistula excision). The surgical technique was a successful closed fistula excision. In the immediate postoperative period there were no complications such as infection, recurrence or worsening of the epiphora, poor cosmetic results, bleeding or damage to the lid structures or nose. The prognosis for patients with congenital lacrimal fistulas is quite good. Many are asymptomatic and those who have symptomatic epiphora or mucoid discharge can be successfully treated by surgery. Several surgical options exist – closed fistula excision, dacryocystorhinostomy (DCR) with fistula excision and fistula excision with nasolacrimal intubation. Symptomatic congenital lacrimal sac fistulas can be treated successfully with excision alone.

The reported health effects of fermented dairy foods, which are traditionally manufactured in Bulgaria, are connected with their microbial biodiversity. The screening and development of probiotic starters for dairy products with unique properties are based exclusively on the isolation and characterization of lactic acid bacterial (LAB) strains. This study aims to systematically describe the LAB microbial content of artisanal products such as Bulgarian-type yoghurt, white brined cheese, kashkaval, koumiss, kefir, katak, and the Rhodope’s brano mliako. The original technologies for their preparation preserve the valuable microbial content and improve their nutritional and probiotic qualities. This review emphasises the features of LAB starters and the autochthonous microflora, the biochemistry of dairy food production, and the approaches for achieving the fortification of the foods with prebiotics, bioactive peptides (ACE2-inhibitors, bacteriocins, cyclic peptides with antimicrobial activity), immunomodulatory exopolysaccharides, and other metabolites (indol-3-propionic acid, free amino acids, antioxidants, prebiotics) with reported beneficial effects on human health. The link between the microbial content of dairy foods and the healthy human microbiome is highlighted.

INTRODUCTION: Polyphenols (PPs) are plant-derived chemical compounds bearing one or more phenolic rings. The most commonly presented dietary PPs include anthocyanins, flavonols, flavanols and phenolic acids. Studies have shown that polyphenols exert a variety of actions including antioxidant, anti-inflammatory, antimicrobial, antiproliferative, cancer protective, cardioprotective, lipid-lowering, and glucose-lowering. Metabolic syndrome (MetS) is a global health issue associated with an increased risk of cardiovascular diseases, type 2 diabetes, and certain types of cancer. AIM: The purpose of this paper is to summarize the current knowledge about the beneficial effects of different polyphenols on the clinical manifestations of metabolic syndrome. MATERIALS AND METHODS: Literature in PubMed, Google Scholar and ScienceDirect has been studied and analyzed. RESULTS: Most data about the beneficial effects of polyphenols is derived from preclinical studies. The clinical trials involving polyphenolic compounds in subjects with MetS are limited, comprise a small number of participants, and the duration is short. CONCLUSION: Numerous studies show promising effects of polyphenols in improving the biochemical and clinical abnormalities associated with metabolic syndrome but larger, more precise, better controlled clinical trials are necessary to reveal their benefits in clinical practice.

INTRODUCTION: Chronic, low-grade inflammation plays a critical role in the pathogenesis of the metabolic syndrome (MS). Aronia melanocarpa fruits are rich in biologically active compounds—polyphenols, which possess a variety of health benefits including an anti-inflammatory effect. AIM: The aim of this article is to evaluate the effect of polyphenol-rich Aronia melanocarpa fruit juice (AMFJ) on carrageenan-induced acute inflammation in rats with diet-induced MS. MATERIALS AND METHODS: Forty male Wistar rats were included in the experiment. They were allocated into 4 groups: MS, MS+AMFJ 2.5 , MS+AMFJ 5 , and MS+AMFJ 10, all receiving high-fat high-fructose diet and 10% fructose in the drinking water for 10 weeks. The MS group served as a control and was treated daily with distilled water orally, while the other groups received AMFJ at doses of 2.5 mL/kg, 5 mL/kg, and 10 mL/kg, respectively. At the end of the experiment, carrageenan was injected in the left hind paw in order to induce acute inflammation. Paw edema was evaluated with plethysmometer on the 30 th min and 1 st , 2 nd , 3 rd , 4 th , and 5 th hour after the injection. RESULTS: In the MS group, the carrageenan-induced paw edema increased gradually with time reaching the highest value on the 5 th hour. A decrease throughout the whole 5-hour period was observed in groups treated with AMFJ, the effect being most pronounced and statistically significant in MS+AMFJ 5 group on the 2 nd and 3 rd hour. CONCLUSION: Aronia melanocarpa fruit juice treatment in rats with MS resulted in a decrease in the carrageenan-induced paw inflammation. The anti-inflammatory effect might be attributed to the polyphenols in AMFJ.

Introduction Laparoscopic distal pancreatectomy is the gold standard nowadays. The infiltration of splenic artery near to its origin as well as engagement of splenic vein near to its confluence with superior mesenteric vein could be a reason for technical difficulties. In such cases the most easily accessible major landmark is the common hepatic artery. Transection of the pancreatic neck and splenic vein is essential to reach the dorsal aspect of the splenic artery at the level of the celiac trunk. The aim of this video is to present our approach to retroperitoneal access of the splenic artery. Methods We present two cases of laparoscopic distal splenopancreatectomy, one of them for cancer of the pancreatic body, and the other one with pseudocyst of the pancreatic body. Mean age of the two patients was 59.5. Results Totally laparoscopic splenopancreatectomy with hepatoduodenal and celiac lymph node dissection was performed. Peripancreatic invasion near to the origin of the splenic artery was observed. Stepwise pancreatic transection at the neck, followed by transection of splenic vein were done in both cases. In the second one major venous bleeding occured and was managed by clipping and division of the splenic vein. The mean operative time was 240 minutes with insignificant blood loss. The patients had uneventful hospital stay and were discharged on the 7.5th postoperative day. Conclusions Laparoscopic distal pancreatectomy can be technically difficult and should be performed only by surgeons with sufficient experience in both open pancreatic surgery and advanced laparoscopic gastrointestinal surgery.

Summary Desmoid-type fibromatosis is a rare mesenchymal neoplasm with locally aggressive, infiltrating and destructive growth that is not characterized by a metastatic potential. According to their anatomical position, desmoid-type fibromatoses can be divided into three groups: extra-abdominal, intra-abdominal, and fibromatoses of the abdominal wall. Mesenteric fibromatoses account for 8% of the intra-abdominal ones. The latter are characterized by myofibroblastic proliferation and infiltration of both the pelvic and abdominal organs. We report a 26-year-old woman who complained of abdominal enlargement, feeling of heaviness, discomfort and reflux, which symptoms dated back 1-2 months prior to hospitalization. The patient underwent laparotomy due to subocclusive symptoms. Intraoperatively, a tumor sized 30 cm in diameter was found. The tumor originated from the mesentery and infiltrated in the jejunum, the entire ileum, and part of the caecum with perforation towards the abdominal cavity. The histological and immunohistochemical examinations are important for clarification of the diagnosis. The treatment requires a multidisciplinary approach, in which the surgical method has the key role.

AIM: To identify demographic, clinical, metabolomic, and lifestyle related predictors of relapse in adult ulcerative colitis (UC) patients.METHODS: In this prospective pilot study, UC patients in clinical remission were recruited and followed-up at 12 mo to assess a clinical relapse, or not. At baseline information on demographic and clinical parameters was collected. Serum and urine samples were collected for analysis of metabolomic assays using a combined direct infusion/liquid chromatography tandem mass spectrometry and nuclear magnetic resolution spectroscopy. Stool samples were also collected to measure fecal calprotectin (FCP). Dietary assessment was performed using a validated self-administered food frequency questionnaire.RESULTS: Twenty patients were included (mean age: 42.7 ± 14.8 years, females: 55%). Seven patients (35%) experienced a clinical relapse during the follow-up period. While 6 patients (66.7%) with normal body weight developed a clinical relapse, 1 UC patient (9.1%) who was overweight/obese relapsed during the follow-up (P= 0.02). At baseline, poultry intake was significantly higher in patients who were still in remission during follow-up (0.9 ozvs0.2 oz,P= 0.002). Five patients (71.4%) with FCP > 150 μg/g and 2 patients (15.4%) with normal FCP (≤ 150 μg/g) at baseline relapsed during the follow-up (P= 0.02). Interestingly, baseline urinary and serum metabolomic profiling of UC patients with or without clinical relapse within 12 mo showed a significant difference. The most important metabolites that were responsible for this discrimination were trans-aconitate, cystine and acetamide in urine, and 3-hydroxybutyrate, acetoacetate and acetone in serum.CONCLUSION: A combination of baseline dietary intake, fecal calprotectin, and metabolomic factors are associated with risk of UC clinical relapse within 12 mo.

Summary Breast cancer is the most common cancer in women worldwide. The standard for detecting it includes clinical exam, mammography and fine-needle aspiration cytology. Our aim was to establish the role of the tru-cut biopsy in the diagnosis of malignant breast lesions. We provideatwo-year retrospective clinical study defining 98.67%sensitivity, 100%specificity, 100%positive predictive value, 80%negative predictive value and an overall diagnostic accuracy of 98.73%. In 89.1%of the malignant lesions, the sample was adequate to define the receptor status. Therefore, tru-cut biopsy is an easy, cheap, safe and accurate alternative to fine-needle aspiration cytology in the diagnosis of breast lesions.

The purpose of this paper is to investigate the graph-based representation of the data required for the vector space model (VSM) and PMI (pointwise mutual information)-enriched VSM used for text mining (e.g. text classification). The transformation of a dataset containing free text reviews for online stores in a graph-based form is described and its format that allows to be used by Neo4j graph database management system is proposed. Queries for retrieving the data required for training text mining models are considered; the steps and the actions for their modification when receiving new data are specified. The advantages of the proposed graph-based representation in regard to the maintenance and the extraction of current data needed for retraining data mining models are summarized, in order to prevent loss of performance of results from the execution of the respective data mining task.

Literature suggests that oxidative stress (OS) may be involved in the pathogenesis of multiple sclerosis (MS), in which the immune system is known to play a key role. However, to date, the OS in peripheral lymphocytes and its contribution to the disease remain unknown. The aim of the present study was to explore the influence of OS in peripheral lymphocytes of MS patients. To that end, a cross-sectional, observational pilot study was conducted [n = 58: 34 MS and 24 healthy subjects (control group)]. We have measured superoxide production and protein mitochondrial complex levels in peripheral blood mononuclear cells (PBMCs) isolated from MS patients and control. Lactate levels and the antioxidant capacity were determined in plasma. We adjusted the comparisons between study groups by age, sex and cell count according to case. Results demonstrated that PBMCs, specifically T cells, from MS patients exhibited significantly increased superoxide anion production compared to control group (p = 0.027 and p = 0.041, respectively). Increased superoxide production in PBMCs was maintained after the adjustment (p = 0.044). Regarding mitochondrial proteins, we observe a significant decrease in the representative protein content of the mitochondrial respiratory chain complexes I-V in PBMCs of MS patients (p = 0.002, p = 0.037, p = 0.03, p = 0.044, and p = 0.051, respectively), which was maintained for complexes I, III, and V after the adjustment (p = 0.026; p = 0.033; p = 0.033, respectively). In MS patients, a trend toward increased plasma lactate concentration was detected [8.04 mg lactate/dL (5.25, 9.49) in the control group, 11.36 mg lactate/dL (5.41, 14.81) in MS patients] that was statistically significant after the adjustment (p = 0.013). This might be indicative of compromised mitochondrial function. Finally, antioxidant capacity was also decreased in plasma from MS patients, both before (p = 0.027) and after adjusting for sex and age (p = 0.006). Our findings demonstrate that PBMCs of MS patients show impaired mitochondrial redox status and deficient antioxidant capacity. These results demonstrate for the first time the existence of mitochondrial alterations in the cells immune cells of MS patients already at the peripheral level. We acknowledge funding from the Biogen Idec Laboratories (ES-TYS-13-10491), the Spanish Ministry of Economy and Competitiveness (PI-1400328), the Autonomous Catalonia Government (ref. 20145GR1681), the Spanish Network of Multiple Sclerosis (REEM) managed by the Carlos III Health Institute (ISCIII) exp. RD16/0015/0008, and FEDER funds from the European Union (“a way to build Europe”).

Multiple sclerosis (MS) is a complex multifactorial neuropathology. Although its etiology remains unclear, it has been demonstrated that the immune system attacks myelin, leading to demyelination and axonal damage. The involvement of lipids as one of the main components of myelin sheaths in MS and other demyelinating diseases has been postulated. However, it is still a matter of debate whether specific alteration patterns exist over the disease course. Here, using a lipidomic approach, we demonstrated that, at the time of diagnosis, the cerebrospinal fluid of MS patients presented differences in 155 lipid species, 47 of which were identified. An initial hierarchical clusterization was used to classify MS patients based on the presence of 25 lipids. When a supervised method was applied in order to refine this classification, a lipidomic signature was obtained. This signature was composed of 15 molecules belonging to five different lipid families including fatty acids (FAs). An FA-targeted approach revealed differences in two members of this family: 18:3n3 and 20:0 (arachidic acid). These results reveal a CSF lipidomic signature in MS patients at the time of diagnosis that might be considered as a potential diagnostic tool.

The aim of the study was to investigate the effect of polyphenol-rich Aronia melanocarpa (Michx.) Elliot juice (AMJ) on learning ability and memory, and brain morphology of aged rats. A model of healthy male Wistar rats (24 months of age) divided in 2 groups was used: AMJ group supplemented orally with AMJ (10 mL/kg for 105 days) and old control (CO) group without supplementation. Activity cage test showed that AMJ supplemented rats increased the number of vertical movements compared with old controls (p

BACKGROUND: Inflammatory bowel diseases (IBD), including Crohn disease and ulcerative colitis, are chronic and severely debilitating gastrointestinal disorders, with rising prevalence, especially in children. While the etiology of IBD remains poorly understood, gut microorganisms and diet have been implicated in IBD pathogenesis. Interestingly, dietary fibers pass through the small bowel undigested and are fermented within the large intestine by specific gut microbes, promoting gut health by altering the gut microenvironment, modulation of the immune system, and altered energy metabolism. Our previous work indicates an altered balance between commensal and pathobiont microbes in IBD, suggesting one opportunity for the misregulation of fiber fermentation within the IBD gut. Interestingly, specific carbohydrate receptors on the surface of immune cells interact with fibers, such as those expressed by certain species of fungi, driving an inflammatory response. AIMS: Here we hypothesize that the altered microbiota in IBD causes significant changes in fiber fermentation, ultimately driving intestinal inflammation. METHODS: Bacterial growth rates in response to specific fibers were examined by OD600 growth curves. Bacterial fiber fermentation patterns were evaluated by mass spectrometry of SCFAs. The effects of specific fibers on bacterial pathogenicity when co-cultured with human HT29 epithelial cells was measured by gentamicin protection assays and visualized by microscopy. Immunohistochemistry of biopsy tissues collected from pediatric IBD (n=14) and control patients (n=7) was utilised to examine expression levels of fiber receptors expressed on human cells. RESULTS: We have demonstrated that commensal microorganism, isolated live from IBD patients, display a different pattern of fiber fermentation compared to pathobiont species. Specific fibers also increase the invasive potential of these pathobionts. Preliminary immunohistochemistry suggests that there is increased expression of specific carbohydrate receptors in IBD, suggesting an increased sensitivity to unfermented dietary fibers in these patients. CONCLUSIONS: These results suggest that some patients may display a sensitivity to specific dietary fibers due to a lack of appropriate fiber fermenting microbes in their gut. Profiling the patient specific microbiota of IBD patients may allow us to make more specific dietary recommendations to assist in reducing intestinal inflammation in IBD. Comparing in vitro findings to our readily available patient food frequency questionnaires (FFQs) and detailed patient history will allow us to define key disease features of IBD and also identify new and improved treatment options, such as microbe-altering treatments, and tailored nutritional recommendations. FUNDING AGENCIES: CCCCCFC

BACKGROUND: The association between diet and inflammatory bowel disease remains largely unknown. To date, few studies have been conducted to investigate the association between the inflammatory potential of a diet and disease activity in patients with inflammatory bowel disease. AIMS: We conducted this study to evaluate the relationship between dietary inflammatory index (DII) and fecal calprotectin (FCP) levels in a cohort of ulcerative colitis (UC) patients. METHODS: This was a cross-sectional study on adult UC patients who were in clinical remission (partial Mayo250 µg/g which is associated with higher disease activity and increased probability of UC relapse was considered as high. RESULTS: Fifty-nine UC patients were recruited. Their mean age was 40.3 ± 14.2 years and 61% of them were females. Their mean DII score was -0.3 ± 1.9. Patients with high FCP had higher DII scores than patients with low FCP (0.8 ± 1.7 vs. -0.8 ± 1.8, P=0.004). UC patients with a more pro-inflammatory diet (DII score > -0.5 (median value)) were more likely to have high fecal calprotectin in comparison to patients with a less pro-inflammatory diet (44.8 vs. 16.7%, P=0.02, Odds ratio: 4.1, 95% confidence interval: 1.2–13.6). In addition, Spearman analysis suggested a significant correlation between FCP and DII scores (r=0.35, P=0.007). Among different components of DII, FCP was correlated significantly with dietary intake of alcohol (r= -0.29), β-Carotene (r= -0.44), fiber (r= -0.23), polyunsaturated fatty acids (r= -0.22), and vitamin E (r= -0.42). CONCLUSIONS: We found that a pro-inflammatory diet was related to increased FCP in UC patients. These findings suggest that an association between diet and increased disease activity or relapse might be mediated through inflammatory properties of the diet. FUNDING AGENCIES: Alberta Innovates - Bio Solutions

In chronic kidney disease (CKD), hyperphosphatemia-induced inflammation aggravates vascular calcification (VC) by increasing vascular smooth muscle cell (VSMC) osteogenic differentiation, ADAM17-induced renal and vascular injury, and TNFα-induction of neutral-sphingomyelinase2 (nSMase2) to release pro-calcifying exosomes. This study examined anti-inflammatory β-glucans efficacy at attenuating systemic inflammation in health, and renal and vascular injury favoring VC in hyperphosphatemic CKD. In healthy adults, dietary barley β-glucans (Bβglucans) reduced leukocyte superoxide production, inflammatory ADAM17, TNFα, nSMase2, and pro-aging/pro-inflammatory STING (Stimulator of interferon genes) gene expression without decreasing circulating inflammatory cytokines, except for γ-interferon. In hyperphosphatemic rat CKD, dietary Bβglucans reduced renal and aortic ADAM17-driven inflammation attenuating CKD-progression (higher GFR and lower serum creatinine, proteinuria, kidney inflammatory infiltration and nSMase2), and TNFα-driven increases in aortic nSMase2 and calcium deposition without improving mineral homeostasis. In VSMC, Bβglucans prevented LPS- or uremic serum-induced rapid increases in ADAM17, TNFα and nSMase2, and reduced the 13-fold higher calcium deposition induced by prolonged calcifying conditions by inhibiting osteogenic differentiation and increases in nSMase2 through Dectin1-independent actions involving Bβglucans internalization. Thus, dietary Bβglucans inhibit leukocyte superoxide production and leukocyte, renal and aortic ADAM17- and nSMase2 gene expression attenuating systemic inflammation in health, and renal injury and aortic calcification despite hyperphosphatemia in CKD. A grant to A.S.D. and M.J.M. from IRBLleida and Agrotecnio Research collaborative projects from the Consell Social at Lleida University supported initial work, Instituto de Salud Carlos III and co-funded by European Union (ERDF/FEDER) (FIS PI11/00259, PI14/01452, PI17/02181), Plan de Ciencia, Tecnología e Innovación 2013–2017 y 2018–2022 del Principado de Asturias (GRUPIN14-028, IDI-2018-000152), RedInRen from ISCIII (ISCIII-RETIC REDINREN RD16/0009). Investigator support included: NC-L by GRUPIN14-028 and IDI-2018-000152, LM-A by GRUPIN14-028, SP by FICYT; MVA and PV by Educational Grant 2 A/2015 from ERA-EDTA CKD-MBD Working Group; PV and AC by ERA-EDTA fellowships 2011 and 2012; JR-C by MINECO (“Juan de la Cierva” program, FJCI-2015-23849); A.S.D. by Asociación Investigación de Fisiología Aplicada. A.S.D. and M.J.M. are members of the Campus Iberus (Ebro Valley Campus of International Excellence).

Excessive ethanol consumption enhances oxidative stress in the brain by overproduction of free radicals along with disruption of the antioxidant defense. It is suggested that ethanol-induced oxidative stress might be the primary event associated with neuroinflammation, neurotoxicity and neurodegeneration in the central nervous system. In recent years, alcohol-induced oxidative stress has been considered as a key mechanism involved in the neuronal loss in ischemic brain injury, Alzheimer’s disease, Parkinson’s disease, and neurodevelopmental and neuropsychiatric disorders. Given the compelling evidence that oxidative stress is of paramount importance in ethanol-induced neurotoxicity, antioxidant-based therapeutic interventions have been postulated as potentially promising for neuroprotection. However, there are strong recommendations for a more precise characterization of optimal doses, timing, and duration of treatment with antioxidants, as well as the application of combination therapies. Currently, nanoparticle formulations are gaining considerable attention as drug carriers, or therapeutic agents, and noninvasive alternatives of conventional antioxidant supplements. Experimental data have shown that nanoparticles display favorable effects in animal models of oxidative, stress-related, brain disorders.

INTRODUCTION: In modern prosthetic dentistry, there are mainly two approaches when manufacturing any prosthetic restoration: conventional and digital. In these approaches, the methods for reproducing the prosthetic field can be divided into: conventional impression methods, digital impression methods, and combined impression methods. AIM: The aim of the present literature review is to identify the advantages and disadvantages of taking a digital impression over conventional impression, and to determine whether the digital impression is as accurate as a conventional one. MATERIALS AND METHODS: A total of 209 articles were analyzed. The electronic databases of ResearchGate, Embase, Google Scholar, PubMed, and Scopus were used. The search was limited to entire articles written in English and published in peer-reviewed scientific journals. RESULTS: The studied articles were published in the period from 1961 to 2019 and over 60% of them were in the last 10 years. Among these studies, 10 are previous literature reviews, 85 are in vivo clinical trials, 6 are randomized controlled/crossover studies, 11 are controlled comparative studies, 7 are clinical case reports, and 90 are in vitro comparative studies. CONCLUSION: The present study has its limitations due to the fact that it is a literature review. However, we can conclude that the digital impression technique has a number of advantages over the conventional impression technique, one of the most important of which is the reduced patient discomfort.

SUMMARY Purpose: To detect visual disturbances, major symptoms and relationship between them in children between the ages of 3 and 6 years, who spend some time in front of a computer. Material/Methods: In the present study 2823 children attending 23 kindergartens in the city of Pleven, were given inquiry cards. Those with completed questionnaires were examined for visual acuity and convergence. In cases with low vision the children were invited for a detailed eye examination in the Eye Clinic at the University Hospital “Dr G. Stranski” - Pleven. Results: A total of 2332 children responded and were examined (1174 girls and 1158 boys). The age of children is from 3 to 6 years. We found 303 children with subjective complaints in a close work, 163 with low vision and 18 with impaired convergence. Regarding the duration of stay in front of a computer – 159 children stay over 3 hours a day in front of video display, 1228 children spend about 1 hour a day in front of a computer and 945 children do not play on a computer. Conclusion: Nowadays more and more children use computers for recreational purposes at home. From our study it became clear that preschool children overuse their stay in front of computer.