Synthesis, Redox Properties and Antibacterial Activity of Hindered Phenols Linked to Heterocycles.

A series of benzotriazole, cyclic amides and pyrimidine derivatives, containing 2,6-di-tert-butyl-phenol fragments, were synthesized. The redox properties of obtained compounds were studied using the cyclic voltammetry on a platinum electrode in acetonitrile. The oxidation potentials of all substances were comparable to those of BHT. The obtained compounds were tested for their antibacterial activity, and N-(2-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-oxoethyl)isatin (32 µg/mL) exerted good activity against Staphylococcus aureus.

Regression of Walker 256 carcinosarcoma in vasopressin-deficient Brattleboro rats is accompanied by a changed laminin pattern.

Walker 256 carcinosarcoma is a transplantable model of rat carcinoma that originally appeared spontaneously in mammary glands. The growth rate of Walker 256 carcinosarcoma in vasopressin-deficient Brattleboro rats is lower than in WAG rats and their congenic hybrids with normal vasopressin levels. Study of tumor proteins detected essential alterations. Tumor regression starting at the 14th day in Brattleboro rats was accompanied by changes in the laminin pattern. At the 21st day, the concentration of α-chains became twice as low, while ß-chains of laminin showed a sixfold increase compared to the initial equimolar correlation of bands. Congenic hybrids having one active copy of the vasopressin gene to provide a physiological level of hormone against the genetic background of Brattleboro rats show the same laminin alterations as WAG rats. They demonstrated a similar moderate increase of γ-chains and threefold growth of α- and ß-chains of laminin in tumor tissue. It is supposed that vasopressin may be involved in the regulation of relevant local stimuli to trigger renovation of the laminin composition in a course of growing Walker 256 carcinosarcoma.

New PMMA-Based Hydroxyapatite/ZnFe2O4/ZnO Composite with Antibacterial Performance and Low Toxicity.

Polymethylmethacrylate (PMMA) is the most commonly used bone void filler in orthopedic surgery. However, the biocompatibility and radiopacity of PMMA are insufficient for such applications. In addition to insufficient biocompatibility, the microbial infection of medical implants is one of the frequent causes of failure in bone reconstruction. In the present work, the preparation of a novel PMMA-based hydroxyapatite/ZnFe2O4/ZnO composite with heterophase ZnFe2O4/ZnO NPs as an antimicrobial agent was described. ZnFe2O4/ZnO nanoparticles were produced using the electrical explosion of zinc and iron twisted wires in an oxygen-containing atmosphere. This simple, highly productive, and inexpensive nanoparticle fabrication approach could be readily adapted to different applications. From the findings, the presented composite material showed significant antibacterial activity (more than 99% reduction) against P. aeruginosa, S. aureus, and MRSA, and 100% antifungal activity against C. albicans, as a result of the combined use of both ZnO and ZnFe2O4. The composite showed excellent biocompatibility against the sensitive fibroblast cell line 3T3. The more-than-70% cell viability was observed after 1-3 days incubation of the sample. The developed composite material could be a potential material for the fabrication of 3D-printed implants.

Whole genome sequence data of Stenotrophomonas maltophilia SCAID WND1-2022 (370).

The whole genome sequence of a hospital infection agent, Stenotrophomonas maltophilia SCAID WND1-2022 (370), is reported. Raw PacBio generated reads and the genome sequence were deposited at NCBI under BioProject PRJNA754843. The genome comprises two replicons: 4,880,425 bp long chromosome comprising 4524 proteins and functional RNA coding genes and 38,606 bp long plasmid containing 40 CDS. Both replicons were methylated at third cytosine residues of ACCTC motifs. The taxonomic provenance of SCAID WND1-2022 (370) was determined by calculating sequence similarity to the reference genomes at NCBI that showed the highest 97.35% identity to S. maltophilia ISMMS4. Many antibiotic resistance and virulence genes were identified on the chromosome of S. maltophilia SCAID WND1-2022 (370), which include multiple efflux pumps, beta-lactamases, and genes involved in biofilm formation. The plasmid sequence was dissimilar to any known plasmid and seemingly was acquired from a distant microorganism. Plasmid-born genes possibly contributed to the virulence of the pathogens, but not to its drug resistance.

Complete Genome Sequences of Gram-Positive Opportunistic Pathogens Isolated from Hospitals in Almaty, Kazakhstan.

The appearance of drug-resistant pathogens reduces the therapeutic applicability of antibiotics and increases the rate of hospital infections among patients. Complete genome sequences of four Gram-positive clinical isolates of Streptococcus and Staphylococcus were obtained and analyzed to serve as model microorganisms for further studies on drug-induced antibiotic resistance reversion.

Register-based information on thyroid diseases in Europe: lessons and results from the EUthyroid collaboration.

Objective: Registers of diagnoses and treatments exist in different forms in the European countries and are potential sources to answer important research questions. Prevalence and incidence of thyroid diseases are highly dependent on iodine intake and, thus, iodine deficiency disease prevention programs. We aimed to collect European register data on thyroid outcomes to compare the rates between countries/regions with different iodine status and prevention programs. Design: Register-based cross-sectional study. Methods: National register data on thyroid diagnoses and treatments were requested from 23 European countries/regions. The provided data were critically assessed for suitability for comparison between countries/regions. Sex- and age-standardized rates were calculated. Results: Register data on ≥1 thyroid diagnoses or treatments were available from 22 countries/regions. After critical assessment, data on medication, surgery, and cancer were found suitable for comparison between 9, 10, and 13 countries/regions, respectively. Higher rates of antithyroid medication and thyroid surgery for benign disease and lower rates of thyroid hormone therapy were found for countries with iodine insufficiency before approx. 2001, and no relationship was observed with recent iodine intake or prevention programs. Conclusions: The collation of register data on thyroid outcomes from European countries is impeded by a high degree of heterogeneity in the availability and quality of data between countries. Nevertheless, a relationship between historic iodine intake and rates of treatments for hyper- and hypothyroid disorders is indicated. This study illustrates both the challenges and the potential for the application of register data of thyroid outcomes across Europe.

Reduced Walker 256 carcinosarcoma growth in vasopressin-deficient Brattleboro rats.

The growth pattern of carcinosarcoma Walker 256 was studied in rats with different levels of vasopressin in the blood. The Brattleboro rats are unable to synthesize vasopressin in a consequence of deletion in the coding gene. Hybrids from crossbreeding of the mutant Brattleboro and normal WAG rats inherit the one intact vasopressin gene and hold nearly normal hormone level. It was found that non-strain-specific carcinosarcoma Walker 256 intensively grows in WAG rats and their offsprings from crossbreeding with Brattleboro rats, and tumor development is equally terminated in them by death. Carcinosarcoma grows less intensely in Brattleboro rats; the tumor nodes increased only within the first 2 weeks, after which, the tumor began to decrease and eventually disappeared. Infusion of exogenous vasopressin to Brattleboro rats intensifies a tumor growth in the first 2 weeks after the inoculation of Walker 256 cells; however, it does not prevent a following regression and resorption of tumors.

Thyroid Cancer Incidence in Bulgaria before and after the Introduction of Universal Salt Iodization: An Analysis of the National Cancer Registry Data

Background: Thyroid cancer is the most common malignancy of the endocrine system and it has become the fastest growing cancer among women. The suspected risk factors include increased exposure to ionizing radiation during childhood, environmental pollutants, possible iodine deficiency, and excessive iodine exposure. Aims: To analyze the thyroid cancer incidence between 1980 and 2013 in Bulgaria and to determine the incidence rate before and after the introduction of universal salt iodization in 1994 in regions with different iodine deficiency levels. Study Design: Retrospective cohort. Methods: The study was a retrospective analysis of the total number of thyroid cancer cases with all histological types in Bulgaria (thyroid cancer, ICD10 code C73), diagnosed between 01/01/1980 and 31/12/2013, and retrieved from the anonymous cancer registry database of the Bulgarian National Cancer Registry. Age-standardized rates of thyroid cancer per 100,000 persons were calculated for each year of the periods mentioned below by sex and age, utilizing the WHO world reference populations with a special statistical module of the Bulgarian National Cancer Registry's software CancerRegBG, 2011. Incidence rates were reported by age, sex, and period of diagnosis (1980-86, 1987-93, 1994-99, 2000-2006, 2007-2013). Trends among males and females were analyzed separately, as well as by age category: 0-19, 20-44, 45-64, and 65+. Annual percentage changes of age-standardized incidence rates were analyzed by Joinpoint regression to determine trends using the Joinpoint statistical software SEER* Stat Software, Version 4.1.1, 2014. Results: The age-standardized rates of thyroid cancer in Bulgaria has been increasing since 1990, being higher among women compared to men (4.68 vs 2.81). The highest age-standardized rates of thyroid cancer was observed in women in the 2007-2013 period. The only significant joinpoint was recorded in 1990 for females and in 1991 for males. The highest incidence rates was in the Smolyan district, a region with historically existing iodine deficiency and relatively high post-Chernobyl radiation exposure. Conclusion: Our results showed that, in different regions, the age-standardized thyroid cancer rates between endemic and non-endemic differ greatly depending on the radiation dose from the Chernobyl accident. The role of iodine intake in thyroid cancer remains uncertain, but iodine deficiency could be a contributing factor to the increased risk of thyroid cancer.

Economic transition and household food consumption: a study of Bulgaria from 1985 to 2002.

Major economic transitions typically entail changes in the availability of and purchasing power for different types of foods leading to long-term changes in the composition of the diet. Bulgaria, a former Eastern Bloc country, underwent a difficult and protracted transition from a centralized to market economy with acute economic crises and a much slower recovery of income levels than in Poland, the Czech Republic, and Hungary. Using annual data from the Bulgarian National Household Survey, we study changes in the reported consumption of major foods (excluding alcoholic drinks) and their constituent macronutrients from 1985 to 2002, examining also the differences in dietary patterns between the period prior to and following the transition. The consumption of most major food items decreased, resulting in a fall in per capita energy consumption of 429 kcal/day (1.80 MJ/d), following the economic transition of 1991. As expected, the consumption of foods that were more expensive per unit of energy decreased greater than cheaper foods, -34% for animal products and -19% for visible fats, but only -10% for carbohydrates. These changes are related to the changes in income and market prices as well as the general negative trend in economic growth and hyperinflation in the mid-1990s. Thus, Bulgaria experienced a decrease in food consumption without significant changes in the dietary pattern following the economic transition of 1991. The fact that part of this decline may be attributed to continued economic challenges suggests that future transitions in the diet may be expected as economic development proceeds.

Ensuring Effective Prevention of Iodine Deficiency Disorders.

BACKGROUND: Programs initiated to prevent iodine deficiency disorders (IDD) may not remain effective due to changes in government policies, commercial factors, and human behavior that may affect the efficacy of IDD prevention programs in unpredictable directions. Monitoring and outcome studies are needed to optimize the effectiveness of IDD prevention. SUMMARY: Although the need for monitoring is compelling, the current reality in Europe is less than optimal. Regular and systematic monitoring surveys have only been established in a few countries, and comparability across the studies is hampered by the lack of centralized standardization procedures. In addition, data on outcomes and the cost of achieving them are needed in order to provide evidence of the beneficial effects of IDD prevention in countries with mild iodine deficiency. CONCLUSION: Monitoring studies can be optimized by including centralized standardization procedures that improve the comparison between studies. No study of iodine consumption can replace the direct measurement of health outcomes and the evaluation of the costs and benefits of the program. It is particularly important that health economic evaluation should be conducted in mildly iodine-deficient areas and that it should include populations from regions with different environmental, ethnic, and cultural backgrounds.

Transcriptome Characteristics and X-Chromosome Inactivation Status in Cultured Rat Pluripotent Stem Cells.

Rat pluripotent stem cells, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs) as mouse and human ones have a great potential for studying mammalian early development, disease modeling, and evaluation of regenerative medicine approaches. However, data on pluripotency realization and self-renewal maintenance in rat cells are still very limited, and differentiation protocols of rat ESCs (rESCs) and iPSCs to study development and obtain specific cell types for biomedical applications are poorly developed. In this study, the RNA-Seq technique was first used for detailed transcriptome characterization in rat pluripotent cells. The rESC and iPSC transcriptomes demonstrated a high similarity and were significantly different from those in differentiated cells. Additionally, we have shown that reprogramming of rat somatic cells to a pluripotent state was accompanied by X-chromosome reactivation. There were two active X chromosomes in XX rESCs and iPSCs, which is one of the key attributes of the pluripotent state. Differentiation of both rESCs and iPSCs led to X-chromosome inactivation (XCI). The dynamics of XCI in differentiating rat cells was very similar to that in mice. Two types of facultative heterochromatin described in various mammalian species were revealed on the rat inactive X chromosome. To explore XCI dynamics, we established a new monolayer differentiation protocol for rESCs and iPSCs that may be applied to study different biological processes and optimized for directed derivation of specific cell types.

Renal and endocrine changes in rats with inherited stress-induced arterial hypertension (ISIAH).

Hypertensive inbred rats (ISIAH; inherited stress-induced arterial hypertension) present with baseline hypertension (>170 mmHg in adult rats), but attain substantially higher values upon mild emotional stress. We aimed to characterize key parameters related to hypertension in ISIAH. Kidneys, adrenals, and systemic endocrine parameters were studied in ISIAH of different ages and compared to normotensive Wistar albino Glaxo (WAG) rats. Native organs were obtained for Western and PCR analysis. Perfusion-fixed organs were prepared for histopathology and quantitative histochemistry. Plasma renin and adrenal hormones were measured. Renal morphology was unaltered in ISIAH. The hypothalamic-pituitary-adrenocortical (HPA) axis was constitutively upregulated with enlarged adrenal cortices and enhanced plasma corticosterone levels. Plasma renin activity was not different between groups, whereas aldosterone levels were in part reduced. Juxtaglomerular NO synthase type 1, cyclooxygenase type 2, and renin expression were significantly reduced, whereas tubular gene products related to sodium transport (bumetanide-sensitive Na, K, 2Cl cotransporter type 2; thiazide-sensitive Na, Cl cotransporter; epithelial Na channel-alpha; 11beta-hydroxysteroid dehydrogenase type 2) were increased. These data suggest enhanced volume conservation by the kidney. Our data define ISIAH as an attractive model for the renal components determining salt and water homeostasis in hypertension. The specific condition of a basally stimulated HPA axis is highlighted, including the option to study effects superimposed by emotional stress.