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Objective: Effective persuasive communication necessitates message matching; the conveyed message should resonate with the recipient's characteristics, including individual moral values. While studies examining the relationship between moral values and vaccination behavior have been conducted in a limited number of countries, this study seeks to provide evidence on this relationship beyond Western democracies., Methods: A cross-sectional online survey was conducted from November 4 to December 17, 2021, in Russia. Participants reported their COVID-19 vaccination behavior and completed the Moral Foundations Questionnaire, designed to measure the endorsement of moral values (n = 415). Regression analysis was employed to assess the association between each moral foundation and COVID-19 vaccination behavior., Results: Our findings indicate that the moral foundations of Care, Loyalty, Fairness, and Sanctity significantly influence vaccination behavior. Individuals who strongly endorse Fairness (AME = -0.019; 95 % CI = -0.033, -0.005) and Sanctity (AME = -0.016; 95 % CI = -0.031, -0.002) were less likely to be vaccinated. Conversely, individuals endorsing Care (AME = -0.018; 95 % CI = -0.031, -0.005) and Loyalty (AME = -0.015; 95 % CI = -0.028, -0.001) were less likely to report refusal of vaccination. These results remain robust after adjusting for sociodemographic variables related to vaccination barriers., Conclusion: Our findings carry public health implications; an understanding of the moral psychology underlying vaccination behavior can facilitate more targeted and effective health communication. Employing skillfully crafted moral appeals may mitigate negative attitudes toward vaccination and enhance vaccination rates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Lasso peptides, biologically active molecules with a distinct structurally constrained knotted fold, are natural products belonging to the class of ribosomally-synthesized and posttranslationally modified peptides (RiPPs). Lasso peptides act upon several bacterial targets, but none have been reported to inhibit the ribosome, one of the main antibiotic targets in the bacterial cell. Here, we report the identification and characterization of the lasso peptide antibiotic, lariocidin (LAR), and its internally cyclized derivative, lariocidin B (LAR-B), produced by Paenabacillussp . M2, with broad-spectrum activity against many bacterial pathogens. We show that lariocidins inhibit bacterial growth by binding to the ribosome and interfering with protein synthesis. Structural, genetic, and biochemical data show that lariocidins bind at a unique site in the small ribosomal subunit, where they interact with the 16S rRNA and aminoacyl-tRNA, inhibiting translocation and inducing miscoding. LAR is unaffected by common resistance mechanisms, has a low propensity for generating spontaneous resistance, shows no human cell toxicity, and has potent in vivo activity in a mouse model of Acinetobacter baumannii infection. Our finding of the first ribosome-targeting lasso peptides uncovers new routes toward discovering alternative protein synthesis inhibitors and offers a new chemical scaffold for developing much-needed antibacterial drugs., Competing Interests: COMPETING INTERESTS STATEMENT The authors declare no competing interests.

Vaccine hesitancy is one of the major roadblocks to ending the COVID-19 pandemic. However, little is known about individuals' motivators and barriers to vaccination in Russia. We aimed to determine which factors were associated with COVID-19 vaccine acceptance in Russia. We conducted a cross-sectional, online survey across Russia at the end of 2021, during a time with increasing new cases of COVID-19. We used the Health Belief Model to test which of the constructs were associated with vaccine acceptance and controlled for demographic variables in the multivariate logistic regression analysis among our analytic sample of 550 respondents. About one-fifth (18.5%) of our study respondents reported vaccine hesitancy. Our multivariate analysis showed that perceived susceptibility, perceived benefits, perceived barriers, self-efficacy, and friends and family supporting vaccination (cue to action) all contributed to the likelihood of whether or not an individual was accepting of the COVID-19 vaccine. Analysis of our open-ended questions showed that individuals also considered the following factors in making decisions to vaccinate for COVID-19: policy restrictions, less worry, social responsibility, lack of trust, conspiracy theories, concerns about side effects and contraindications. Our results demonstrated the Health Belief Model to be a useful framework for understanding COVID-19 vaccine acceptance in Russia. Our study results highlight the need to focus on health beliefs in order to develop interventions to improve vaccine acceptance., Competing Interests: Declaration of conflicting interestsThe authors have no conflicts of interest to declare.

Background and Objectives : One of the members of the neurotrophin (NT) family is the brain-derived neurotrophic factor (BDNF). In addition to its role in the nerve system, it has been found to play a role in lung health and diseases. Materials and Methods : The serum concentrations of BDNF were assessed in 57 patients with COPD and in 19 control individuals and the possible associations of BDNF with the spirometric indexes and disease stages were explored. Results : We did not find a significant difference between the serum concentrations of BDNF of patients and controls ( p = 0.521). A significant negative correlation of the serum BDNF levels with the age of the patients (Rho = -0.279, p = 0.036) was observed. In addition, a borderline negative correlation with the age of disease onset (Rho= -0.244, p = 0.063) was also found. When analyzing these correlations in different genders, we found stronger statistical significance in male patients (Rho = -0.398, p = 0.009; and Rho = -0.419, p = 0.006), while no such significance was found in females ( p = 0.574 and p = 0.342). The analyses of the possible relations of serum BDNF concentration with the spirometric parameters in the whole group of patients did not reveal any significance ( p = 0.231 for FEV1%pr. and p = 0.271 for FEV1/FVC%). However, when the patients were dichotomized on the basis of smoking habits, we obtained a strong positive correlation between BDNF and FEV1%pr. (Rho = 0.501, p = 0.048) in non-smokers, but strong negative correlations with FEV1%pr. (Rho = -0.468, p = 0.003) and with FEV1/FVC% (Rho = -0.331, p = 0.040) in ex/current smokers. Non-smokers with moderate disease (GOLD II) had higher BDNF serum concentrations than patients with GOLD stage III/IV ( p = 0.031). In ex/current smokers, there was an opposite association ( p = 0.045). Conclusions : The results of our study suggest that the expression and secretion of BDNF are changed in COPD, but its effects and functions may differ according to the smoking history of the patients.

Chronic inflammation creates tumor microenvironment (TME) that facilitates colorectal cancer (CRC) cell proliferation, migration, metastasis, and tumor progression. Interleukin-6 (IL-6) is a proinflammatory cytokine with a pleiotropic effect on CRC development. We aimed to evaluate IL-6 expression in tumor cells and in immune cells in TME, to assess the serum level and IL6 -174 G/C genotype distribution and to correlate the results with selected morphologic and clinical parameters that may add useful information in understanding the mechanisms of human CRC progression. A total of 153 patients with CRC were recruited in the current study. We assessed the IL-6 serum concentration through the ELISA method, the expression of IL-6 in tumor and in immune cells by immunohistochemical and double immunofluorescence staining, the MSI status by immunоhistochemistry for 4 mismatch repair (MMR) proteins, and the genotype distributions for IL6 -174G/C (rs1800795) single-nucleotide polymorphism through PCR-RFLP method. Our results showed that serum IL-6 level were increased in CRC patients as compared with healthy controls (P<0.0001), and in patients with cancers with advanced histologic type (type IV). However, the higher concentration (above the median of 55.71 pg/mL) was with borderline association with longer survival of the patients after surgical therapy (P=0.055, Log rank test). We also found that IL-6+ immune cells prevailed in the invasive front (IF) of tumors compared with the tumor stroma (TS) (P<0.0001). More IL-6+ cells were recruited in the tumors with less advanced histologic type (I+II), with stronger inflammatory infiltrate in the IF, in early pTNM stages (I+II), without lymph node and distant metastases and the higher levels of IL-6+ cells, especially in the IF, were associated with longer survival (P=0.012). The results of our study suggest that although the serum levels of IL-6 are higher in CRC, the increased IL-6+ cells in tumor microenvironment, both in the invasive front and in tumor stroma, as well as the higher serum levels are associated with good prognostic variables and longer survival of the patients mainly in the early stages of CRC., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Only one-third of patients with advanced MSS/pMMR endometrial cancer exhibit a lasting response to the combination treatment of Pembrolizumab and Lenvatinib. The combined administration of these two drugs is based on Lenvatinib's ability to modulate the tumor microenvironment, enabling Pembrolizumab to exert its effect. These findings underscore the importance of exploring tumor microenvironment parameters to identify markers that can accurately select candidates for this type of therapy. An open non-randomized observational association study was conducted at six clinical centers, involving a total of 28 patients with advanced MSS/pMMR endometrial cancer who received Pembrolizumab and Lenvatinib therapy. Using TSA-associated multiplex immunofluorescence, we analyzed the proportion of CD8+ T lymphocytes, CD20+ B lymphocytes, FoxP3+ T regulatory lymphocytes, and CD163+ macrophages in tumor samples prior to immunotargeted therapy. The percentage of CD20+ B lymphocytes and the CD8-to-CD20 lymphocytes ratio was significantly higher in patients who responded to treatment compared to non-responders (responders vs. non-responders: 0.24 (0.1-1.24)% vs. 0.08 (0.00-0.15)%, p = 0.0114; 1.44 (0.58-2.70) arb. unit vs. 19.00 (3.80-34.78) arb. unit, p = 0.0031). The sensitivity and specificity of these biomarkers were 85.71% and 70.59%, and 85.71% and 85.71%, respectively. The proportion of CD20+ B lymphocytes and the CD8-to-CD20 lymphocytes ratio in the stroma of endometrial cancer serves as both a prognostic marker of response to immunotargeted therapy and a prognostic factor for progression-free survival in patients.

The studies on the demand for healthcare in low- and middle-income countries rarely take into consideration the fact that many people spend their income on self-treatment and professional treatment. The estimation of the income elasticity of demand for self-treatment and professional treatment can show a more precise picture of the affordability of professional care. This paper contributes to the discussion around estimates of income elasticity of health spending and discussion whether professional care and self-treatment are close to a luxury good and inferior good respectively in a middle-income country. We apply the switching regression model to explain the choice between self-treatment and professional healthcare via estimates of the income elasticity. Estimates are made with the use of the Russian Longitudinal Monitoring Survey - Higher School of Economics (RLMS-HSE), a nationally representative survey. While individual expenditure on professional treatment is higher than that on self-treatment, our estimates show that expenses on professional treatment can be income inelastic except when spending on medicines prescribed by a physician that are elastic. The results also indicate that cost of self-treatment is income elastic. In all cases, the considered income elasticities are statistically insignificant between professional and self-treatment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objectives : The role of transforming growth factor-beta1 (TGF-β1) has been widely studied in the context of carcinogenesis. It has been involved in the pathogenesis of primary brain tumors or brain metastases due to its pleiotropic effects on immune regulation and tissue homeostasis. In line with recent findings, the aim of the current study was to examine the role of circulating TGF-β1 and the -509C/T functional polymorphism (rs1800469) in the TGFB1 gene promoter in the susceptibility and progression of primary brain tumors and brain metastases among patients from the Bulgarian population. Materials and Methods : Cases with a confirmed diagnosis were genotyped by the polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). Serum TGF-β1 levels were determined by ELISA. Immunohistochemical evaluation of the expression of TGF-β1 and the TGF-β1 receptor-type II was conducted. Results : We observed that TGF-β1 serum levels correlate with the genotype and are sex-related. TGF-β1 serum levels were significantly elevated in patients compared to controls. Additionally, the T/T-genotype determined higher circulating levels of the cytokine. The same genotype determined the shorter median survival after surgery for the patients. The immunohistochemical analysis revealed a statistical tendency: cases expressing TGF-β1 in the cytoplasm had elevated levels of the cytokine in the serum compared to the negative cases. Conclusions : Overall, our results indicate a negative effect of the T-allele on the predisposition and prognosis of brain malignancies, and the genetically determined higher TGF-β1 serum levels might contribute to the worse prognosis and metastatic capacity of brain malignancies.

There is limited information about how the mental health of people has changed over time during the COVID-19 pandemic in low- and middle-income countries. In a cross-sectional study, we identified factors associated with psychological distress at two periods immediately after two peaks of the COVID-19 pandemic in Russia. Data were collected via online surveys. In May-June 2020, we surveyed 373 respondents across Russia. In January-February 2021, we surveyed 743 people, using the same approach for survey distribution. With Kessler-10 as a measure of psychological distress, we used regression analysis to determine factors associated with higher psychological distress among Russians. Levels of psychological distress were high in both time periods and did not significantly change between the surveys. Having had COVID-19, losing one's job, experiencing problems accessing healthcare, and changing drinking behaviour during the pandemic were associated with higher psychological distress. Apart from getting sick or worrying about the virus, psychological distress is affected by restrictions and the consequences of the pandemic situation. As the COVID-19 pandemic continues, actions are needed to address the mental well-being of the population in Russia.

Background : Interleukin (IL)-17A and IL-17F, expressed mainly by a novel subset of CD-positive (+) T-helper (Th) cells of the immune system, has been closely related to inflammatory conditions underlying colorectal cancer pathogenesis. Accordingly, we conducted a case-control study to investigate the association of common single nucleotide polymorphisms (SNP) in the IL17A and IL17F genes (rs2275913 and rs763780, respectively) with the susceptibility and severity of CRC patients from the Bulgarian population. Methods and Materials : 136 patients with histologically confirmed CRC diagnosis and 116 healthy individuals were recruited in the present study. Genotypes were determined by the restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) technique. Results : The IL17A heterozygous A/G-genotype was overrepresented among the control group ( p = 0.003). Additionally, the carriers of the heterozygous A/G-genotype had a 2.39-fold lower risk for CRC compared to the G/G-genotype (OR = 0.418, p = 0.006). Our results also indicated that in the advanced CRC stages (III + IV) the heterozygous genotype (A/G) appeared to be less frequent ( p = 0.024, χ 2 -test). Among the patients with detected distant metastases, the A/G-carriers were the smallest part (14.3%) compared to the homozygous genotypes A/A (42.9%) and G/G (42.8%), p = 0.006. There was no association of the studied IL17F rs763780 SNP with susceptibility and severity of CRC among the studied subjects, although the heterozygous C/T-carriers had shorter median survival compared to the T/T-carriers ( p = 0.129). Conclusions : Our study finds a protective role of heterozygosity for the IL17A -197A/G SNP and negative effects of the A-allele on CRC progression.

A 3-month-old female infant with meningo-encephalitis caused by Salmonella enterica Paratyphi B var. Java is described. The aetiological agent was confirmed in six CSF samples; however, none of the blood or faecal samples was positive for the same pathogen. The presence of the bacteria was confirmed in the CSF by culture, serology and Multiplex PCR assay. The infant developed dilated subarachnoid spaces and right-sided hemiparesis associated with the persistent bacterial meningo-encephalitis. She was re-admitted 2 weeks after recovery and initial discharge from hospital owing to recurrence of S. enterica Paratyphi B bacteria in the CSF and the development of large bilateral subdural effusions in the brain. Computed tomography and the clinical course confirmed dynamically progressive meningo-encephalitis. Following further parenteral antibiotics and symptomatic treatment, the child's condition improved. After a total of 24 days in the PICU, she was sufficiently improved to be discharged with a residual right-sided hemiparesis. However, sadly she died a week after discharge. Abbreviation: ALT: alanine aminotransferase; API: analytical profile index 20 E-test; AST: aspartate aminotransferase; CRP: C-reactive protein; CSF: cerebrospinal fluid; CT: computed tomography; EUCAST: European Committee on Antimicrobial Susceptibility Testing; MDCT: multi-detector computed tomography; PCR: polymerase chain reaction; PICU: paediatric intensive care unit; RBC: red blood cells; VITEK: automated instrument for identification/antimicrobial susceptibility testing; WBC: white blood cells.

Purpose: The EQ-5D survey instrument is routinely applied to general and patient specific populations in many countries, as a means of measuring Health Related Quality of Life (HRQOL) and/or informing Health Technology Assessment. The instrument is the subject of growing interest in the Russian Federation, as too is Health Technology Assessment. This research is the first to systematically present the EQ-5D-3L nationally representative population norms and to examine the socioeconomic and socio-demographic characteristics of the instrument among a representative sample of the Russian population., Methods: Based on a nationally representative health and well-being survey of the Russian population, conducted in November 2017, we establish the descriptive results, including the EQ-VAS and the EQ-5D Index, by age and gender, examine the correspondence between the EQ-5D health classifications and the separate EQ-VAS scores, and draw on a set of augmented logistic regressions to evaluate the association between the presence of problems in each dimension and various socio-economic and health-related characteristics., Results: We find strong evidence that the EQ-5D instrument is sensitive to underlying observed and latent health experiences, that it mirrors many of the characteristics familiar from other settings but that there are Russian specificities which merit further research, particularly with respect to the anxiety/depression dimension of the instrument., Conclusion: This research represents an important landmark for HRQOL studies in Russia as well as for the prospects of continuing to develop the scholarly and practical infrastructure necessary for Russian Health Technology Assessment to advance., Competing Interests: The authors declare that there are no relevant conflicts of interest.

Control of the COVID-19 pandemic requires significant changes in people's health behaviors. We offer this multidisciplinary perspective on the extent of compliance with social distancing recommendations and on coping with these measures around the globe in the first months of the pandemic. We present descriptive data from our survey of 17,650 respondents across 18 countries and territories in June 2020. The majority of respondents worried about contracting the virus. Nearly all engaged in at least some preventive behaviors, particularly handwashing, mask wearing, and avoiding social events. Most reported that it would be difficult to continue these behaviors for more than a few months, and about half reported feeling more anxious since the start of the pandemic. Commonly reported coping behaviors included news consumption, watching television, and sleeping. Our cross-national study highlights areas for developing and implementing health behavior interventions in the global fight to stop the spread of COVID-19.

This paper contributes to the discussion around ex-post (increased utilisation of health care) and ex-ante (changes in health behaviours) moral hazard in supplemental private health insurance. Applying a range of methodologies to data from the Russian Longitudinal Monitoring Survey-Higher School of Economics we exploit a selection mechanism in the data to compare the impact of workplace provided and individually purchased supplemental health insurance on the utilisation of health care, on a range of health behaviours and on self-assessed health. We find compelling policy-relevant evidence of ex-post moral hazard that confirms a theoretical prediction and empirical regularity found in other settings. In contrast to other empirical findings though, our data reveals evidence of ex-ante moral hazard demonstrated by clear behavioural differences between those with self-funded supplemental health insurance and those for whom the workplace finances the additional insurance. We find no evidence that either form of insurance is related to improved self-assessed health.

In June 2018, in the city of Sofia, Bulgaria, 40 children from four different kindergartens suffered from salmonellosis caused by S. enteritidis. They were reported to have consumed food prepared and delivered by a private catering service. The patients had fever, diarrhea, and some had vomiting and abdominal pain. Sixteen of them were treated in hospital, and the other 24 received home treatment. Some of the outpatients received antibiotic treatment despite WHO recommendations. All 40 isolates were positive for O: D, H: gm and H: m, and were confirmed to be Salmonella enteritidis, respectively. Using conventional and molecular methods, such as serotyping, Multiplex-PCR and PFGE, it was confirmed that the strains were epidemiologically related. Based on molecular genetic methods, we established that the epidemic outbreak had a common origin: contaminated food delivered by a private catering service, which was consumed at all four kindergartens.

A characteristic feature of inflamed lungs in bronchial asthma (BA) is airway remodeling. Due to limited information on this topic in the literature, we aimed to explore the possible role of polymorphisms in the promoter region of the macrophage elastase gene MMP12 82A>G (rs2276109) as a predisposing factor for BA in an ethnic Bulgarian population. Using restriction fragment length polymorphism analysis of polymerase chain reaction-amplified fragments (PCR-RFLP), we performed genotype analysis of 58 patients and 119 control individuals. We found statistically significant differences in the distribution of genotypes (P = .008) and alleles (P = .004) between patients and nonaffected controls. In the dominant model, carriers of the G allele genotypes had 3.6-fold lower risk for BA, compared with those with the AA genotype, after adjustment for age and sex (odds ratio [OR], -0.277; 95% confidence interval [CI], .12-.65; P = .003). The results of our study suggest that the variant G allele of the MMP12 -82 A>G promoter polymorphism might be considered protective for development of BA in ethnic Bulgarian adults residing in central Bulgaria.

Background: Anti-inflammatory cytokines such as interleukin (IL)-10 and transforming growth factor (TGF)-β1 have a complex role in the development of colorectal cancer (CRC). Dendritic cells (DCs) are the cellular component of the inflammatory microenvironment in the tumor and infiltration of tumors by DCs is associated with better prognosis and fewer metastases., Methods: In the present study, we explored the role of two single nucleotide polymorphisms (SNPs) in the promoter regions of TGFB1 and IL10 genes and their associations with infiltrating DCs in CRC.A case-control study was designed. Genotyping was performed via the polymerase chain reaction-restriction fragment length polymorphism method and DC infiltration was determined immunohistochemically., Results: For the TGFΒ1 -509C/T SNP, we found that the T allele was less frequent in patients than in controls (p = 0.031) and the TT-genotype had a 2.74-fold lower risk for CRC than the CC-genotype (odds ratio = 0.365, 95% confidence interval = 0.15-0.88, p = 0.015). Additionally, the TT carriers had the shortest median survival (14.4 months) (p = 0.045). The C-allele genotypes had a significantly longer survival compared to TT carriers (p = 0.018). The CC genotype was associated with a lower cellular density of CD11c in the invasive margin of the tumor (p = 0.033), whereas there was an opposite finding for CD83+ DCs (p = 0.037). Carriers of A-allele genotypes of the IL10 -1080A/G SNP had significantly lower CD83+ cells (p = 0.046) in the tumor invasive margin., Conclusions: The T-allele of the TGFB1 -509C/T SNP might be a protective factor for development of CRC, although, in the course of the disease, this variant allele might be associated with more unfavorable prognosis of the patients., (Copyright © 2018 John Wiley & Sons, Ltd.)

Chronic inflammation and remodelling of the small airways are features related to chronic obstructive pulmonary disease (COPD). In the current study, we aimed to explore the possible role of MMP12 -82 A > G (rs2276109) promoter polymorphism in the development of COPD in a population from Bulgaria (167 patients with COPD and 119 control individuals). The genotype and allele distributions differed significantly between COPD patients and controls (p = .010 and p = .043, respectively, χ 2 test). The genotypes containing at least one variant G allele (AA + GG) were more frequent in the control group than in patients (36.1% vs. 22.2%) determining 2.96-fold lower risk for COPD after adjustment for age, sex and smoking habits (OR = 0.338, 95%CI: 0.168-0.682, p = .002). Our results suggest that carriers of genotypes with at least one copy of minor G allele of rs2276109 might have lower risk for COPD development, with no marked effect on the lung function and severity of the disease.

Purpose: Chronic inflammation is a key component in the development and progression of colorectal cancer (CRC). A notable hallmark of the inflammation process is the release of pro-inflammatory cytokines by infiltrating cells of the immune system. Defects in dendritic cells (DCs) recruitment, maturation and cytokine release are a hallmark of the CRC strategy to escape immune surveillance.The purpose of our study was to evaluate the possible role of IL-12B polymorphism in the promoter region of the IL-12B gene (rs17860508) as a genetic factor contributing to the risk for CRC development. Additionally, we aimed to evaluate the influence of this polymorphism on DCs infiltration in tumor microenvironment., Methods: IL-12Bpro polymorphism was genotyped by Amplification Refractory Mutation System- Polymerase Chain Reaction (ARMS-PCR). Immunohistochemistry was performed for DCs infiltration., Results: Statistically significant correlation between the expression of S100 and CD1a DCs and the 11- genotype of the studied polymorphism was found. No statistically significant difference in genotype distribution between cases and controls was observed (p=0.163). Analysis of the overall survival (OS) of genotyped patients revealed a tendency among the carriers of the 22-genotype to have shorter survival of 36 months versus the 11- and 12-cariers- 61 months (log rank, p=0.117)., Conclusions: The IL-12Bpro polymorphism does not constitute a risk factor for CRC development. However, genotype-11 might have a complex role in the recruitment and maturation of DCs in tumor microenvironment.

Background: The aberrant activation of Wnt signalling pathway may be a common denominator for the development of thyroid tumorigenesis. It was announced that the loss of E-cadherin rather than β-catenin mutation represents a crucial event in determining the degree of differentiation of thyroid carcinomas., Aim: The aim of the study was to evaluate the expression of E-cadherin and β-catenin in the thyroid cancer tissue and to correlate these data with some histological and clinical parameters of the tumours., Material and Methods: We investigated 112 patients, having thyroid tumours - papillary, follicular, anaplastic and oncocytic carcinomas immunohistochemically with antibodies against E-cadherin and β-catenin. Survival analyses were done., Results: E-cadherin expression was focally retained in the tumour cell membranes and the tumour cell cytoplasm of the papillary, follicular and oncocytic thyroid cancers, weather in anaplastic cancers it was almost lost (p = 0.0042, and p = 0.019, respectively, Fisher's Exact Test). The expression of β-catenin in tumour cytoplasm and membrane in papillary cancers was higher as compared to that in the other tumours (p = 0.111, and p = 0.0104, respectively)., Conclusion: Not surprisingly, the presence of aberrant expression of E-cadherin and β-catenin in thyroid cancer has been associated with better patients' prognosis and better differentiated tumour histology.

The aim of this study was to examine the expression of TGF-β1 and TGF-β receptor type II (RII) and the impact of the -509C>T single nucleotide polymorphism (SNP) in the gene in relation to clinicopathological factors in gastric cancer (GC). Using immunohistochemistry we investigated 43 patients with GC for expression of TGF-β1 and TGF-β-RII. Consequently, RFLP-PCR was performed to analyze the presence of -509C>T polymorphism in the TGF-β1 gene. We found that 72.1% of GCs had cytoplasmic TGF-β1 expression and 27.9% were negative. The TGF-β1 receptor type II was expressed on tumor cell membranes in 58.1%. TGF-β1 positivity in tumor cytoplasm correlated positively with TGF-β1-RII expression in tumor cytoplasm in 67.4% of cases (2 = 8.02; p = 0.005). Also, the results showed that patients with low and moderate tumor differentiation had TGF-β1-RII positivity in 53.3% and 81.8% resp. (2 = 6.58; p = 0,037). The analysis of genotype distribution of the -509C>T SNP in the promoter region of TGF-β1 gene and clinical stage distribution revealed that among the 32 patients in III-IV clinical stage 53.1% were heterozygous (TC), 34.4% were homozygous for the C-allele and 12.5% were homozygous for the variant T-allele (2 = 3.31; p = 0.069). In conclusion the expression of TGF-β1 was related to shorter survival time and rapid progression for the GC patients. Additionally, the variant T-allele of the studied polymorphism was associated with worse prognosis for GC patients.

The aim of the study was to assess the expression and significance of HER2 and HER3, and Ile/Val single nucleotide polymorphism (SNP) of HER2 in lung cancer patients. Thirty seven cases of lung cancer were investigated immunohistochemically for HER2 and HER3 expression. PCR followed by restriction fragment length polymorphism (RFLP) was used to analyze the presence of HER-2 SNP at codon 655 in 20 samples. The results were compared with clinical and pathological parameters of investigated patients.We found that 100% of the cases were negative for HER2, 29.7% were with moderate or strong HER3 expression and 70.3% of the tumors-without or with low expression for HER3. Lymph node metastasis were found in 40% of HER3 positive cases (χ(2) = 4.752; p = 0.029). Moderately-differentiated tumors do not express neither of investigated markers (χ(2) = 6.719; p = 0.035). HER2 RFLP-PCR analysis showed genotype AG in five patients (25%) and the rest of 15 cases (75%) had АА (Ile/Ile) genotype. Patients with metastasis had genotype АА (Ile/Ile) in 80% and genotype AG (Ile/Val) in 20% (χ(2) = 2.857; p = 0.091).Our results indicate that SNP in HER2 codon 655 and investigation of HER2 and HER3 expression could be helpful to outline the prognosis for patients with lung adenocarcinoma.

Microsatellite instability (MSI) is involved in the pathogenesis of about 30% of endometrial cancer cases. In accumulating data from the past few years MSI is shown to have both clinical and prognostic value. In the present work we are discussing the components and molecular mechanisms of functioning of the mismatch repair system (MMR). MSI is a hallmark of endometrial tumors with DNA MMR deficiency. We summarized the main pathways for accumulating mutations in coding and non-coding DNA sequences, which is a result of errors during replication of microsatellite tandem repeats. A few studies rising valuable conclusions about the correlation between MSI and endometrial cancer are revised.

Aim and Background: The aim of this study is to analyze the main clinical and pathologic characteristics of radiation-induced breast carcinomas (BC) following treatment for Hodgkin's disease (HD) and to identify the risk factors for their induction. To create a mathematical model for the prediction of expected age at which a BC might develop based on the age at treatment for HD., Materials and Methods: Thirty-nine cases of women with BC that developed after treatment for HD in puberty or adolescence were analyzed retrospectively. The median age at initiation of treatment for HD was 12.9 years (9-21). The median age at diagnosis of the second malignancy - breast carcinoma was 32.4 years (22.9-39)., Results: THE DISTRIBUTION OF PATIENTS ACCORDING TO THE CLINICAL T STAGE OF BREAST CANCER WAS AS FOLLOWS: 11 patients with T1 stage BC (28%), 22 with T2 stage (56%) and 6 with stage T3 (16%). Prevalent were tumors localized in the lateral breast quadrants. The observed 5 year survival was 95%., Conclusion: The risk of solid tumors, especially breast cancer, is high among women with HD disease who were treated with radiotherapy in their childhood. In this article, we propose a specific mathematical age formula which could be used as predictive equation when the age of the treatment for HD is in the range between 9 and 21 years. Systematic screening for breast cancer in these patients would be significantly important for their health and could improve their survival.

The proton conductivity of a Nafion 112 membrane is measured with a high spatial resolution using electrochemical atomic force microscopy. Image analysis reveals an inhomogeneous conductivity distribution which is attributed to the limited connectivity of hydrophilic domains. This information relates to the micro-morphology which is due to phase separation of the hydrophobic polymer backbone and the hydrophilic pendant groups. The direct images relate to a different length scale and are complementary to the x-ray diffraction investigations which provide only average information. Furthermore, the measured current values reveal an interesting correlation with the size of the conductive areas. A bimodal conductivity distribution suggests that there are different mechanisms which contribute to the proton current in Nafion. Additionally, time dependence in local conductivity is found and interpreted in terms of redistribution of water in the membrane. A statistical analysis of the current distribution is performed and compared with theoretical simulations. Evidence is found for the existence of a critical current density. On a timescale of seconds the response of the conductive network is probed by applying voltage steps to the atomic force microscope tip.

High membrane conductivity is one of the key parameters in polymer electrolyte fuel cell applications. We introduce an electrochemical atomic force microscopy method that provides simultaneously the surface topography of a Nafion 112 membrane and the conductivity of ion channels with an unprecedented resolution of ca. 10 nm. For given conditions, a large fraction of the channel ports is found to conduct exactly the same number of protons per unit time. This is taken as evidence for an optimum pore size and structure for proton conduction, or alternatively, for an efficient connectivity of the ion channel network, so that the same conductivity is measured at all exit pores. The time response following a potential step and the influence of the relative humidity on the transport properties is investigated. The method will be of relevance for tailoring the production technology to yield an optimised micromorphology, and it permits detailed tests of membrane models and provides data for theoretical modelling of proton conductivity.

The aim of the study is to make retrospective analysis of 9 years experience in the feeding of praematuries and high risk newborn in that ward in First City Hospital-Sofia with formula milks "Nenatal" and "Nutrilon-premium". 721--42.4% from all babies in this period were feed with those formulas. With Nenatal only--11.8%, with Nutrilon-premium 88.2%. This the fact is due that all babies under 2000 gr. were fed with Nenatal, and after reaching 2000 gr.--with Nutrilon-premium. The results confirm that Nenatal is right formula for feeding of low and very low birth weight infant, due to its special content and qualities. The results from Nutrilon-premium illustrated that mean gain weight is the biggest in I grade of prematurity--33 grams, followed by matures--30 gr, after them II grade--29 gr., III grade--27 gr., IV grade--26 gr. As a conclusion we may say that mean gain weight for all groups is 29 grams. Consuming all gain weight of the babies feeding with Nutrilon-premium data appear that the biggest is in III of prematurity--1499 grams, followed by IV grade--1418 gr., I grade--1341 spama, II grade--1219 gr., and last matures--745 gr.

Studied was the morphologic picture in a total of 13 calves spontaneously intoxicated with furazolidon following its overrating and use once and severalfold as a therapeutic means against infectious enteritis. There were hemorrhages in the subcutaneous tissue and the muscles, kidneys, abomasum, spleen, and heart as well as liver dystrophia and hyperemia and edema of the leptomeninges and the brain cortex. Histologically, there were hyperemia, strong and diffuse pericellular and perivascular edema of the cerebrum and the cerebellum with degenerative changes in the Purkinje layer, fatty degeneration and biliary thrombi in the liver, hemorrhages and activation of the endothelial cells and glomeruli of the kidneys, hyperemia and fatty infiltration of the myocardium, and hemorrhages in the spleen.

Pathomorphological and biochemical investigations on liver and blood serum laying hens affected by the liver obesity syndrome were carried out. It was established that the mortality due to the liver obesity syndrome varies within the range of 3.1 and 3.7% for the entire period of exploitation. A rise in mortality is observed in case fodder mixtures with higher peroxide and aldehyde number are prepared. Besides the typical changes in the liver, the pathologo-anatomical investigation established varying in its expression duodenitis of rupture of the liver and hemorrhage. In hens suffering from advanced liver obesity an increased content of total protein in the blood serum was observed. The relative and absolute content of prealbumens and albumens was also higher, while the content of globulins was relatively lower. The content of beta-lipoproteins was raised and total lipids in the blood serum were considerably increased. The investigation on total lipids and lipid fractions in the liver established a correlation between the extent of obesity and the content of total lipids. A trend toward increasing the total and particularly the esterificated holesterin was evident in affected birds. The chemical investigation of various lots of fodder mixtures established often cases of rancid fats, which was manifested by high values of the peroxide and aldehyde number. The aminoacid composition of fodder also varied too much. It is assumed that besides the genetic control of liver obesity rancid fats and insufficient content of essential amino acids in the fodder mixtures also lead to an increased mortality percentage in the affected birds.

Use was made of Wistar albino rats in which an inflammation was induced via the simultaneous injection of caraginan and prostaglandin E1 in order to evaluate the antiinflammatory activity of 6 freeze dried plant extracts. It was found that with such model of inflammation the inflammatory effect of caraginan was strongly enhanced, which was accompanied by the rapid and prolific white blood cell extravasates. The freeze-dried extracts of St. John's-wort (Hypericum perforatum L.), potmarigold calendula (Calendula officinalis L.), camomile (Matricaria chamomilla L.) and plantain (Plantago lanceolata L. et Pl. major L.) were found to suppress both the inflammatory effect and the leukocyte infiltration. The extracts of symphytum (Symphytum officinale L.) and those of flax seed (Linum usitatissimum L.) did not inhibit the inflammation, however, they suppressed the leukocyte infiltration at the 3rd and 4th hour of the induced inflammation.