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Background. Individual molecular characteristics of a tumor can serve as a basis for a tailored approach to therapy, prediction of the disease course and outcome, and timely treatment correction in cancer patients. Tumor genomic profiling allows for a more precise tumor assessment in an individual manner. Accurate identification of the HER2 status of a breast tumor is crucial for clinical decisions and appropriate treatment strategy.Aim. To increase the efficacy of systemic therapy for breast cancer, reduce inappropriate prescribing, and ensure a tailored approach to systemic breast cancer therapy using the information on individual molecular characteristics of the tumor.Materials and methods. We explored the expression of 100 genes involved in breast cancer development in 106 tumor samples from patients with metastatic breast cancer. We used the nCounter technology based on direct digital target detection using color-coded molecular barcodes. We analyzed the expression of 28 genes with a high predictive value for breast cancer.Results. The nCounter technology allowed us to perform semiquantitative assessment of the expression of 28 genes in tumor tissue samples. We compared the expression of ERBB2 and HER2. The HER2 expression between 252.32 and 6000 barcodes was equivalent to HER2 (0) status; between 6000 and 9196.25 barcodes, to HER2 (1+); between 9196.25 and 15022.46, to HER2 (2+/ISH±); and 15022.46 barcodes, to HER2 (3+). In case of HER2 (3+) and ERBB2 below 6000 barcodes, the result was considered false positive. In case of HER2 (0) or (1+) and ERBB2 above 15 000 barcodes, the result was considered false negative. In 18 tumors, the discrepancies in the results meant two principally different breast cancer subtypes requiring different treatments; in 2 cases, the discrepancies were in the level of HER2 expression.Conclusion. HER2 testing should be performed on an excision sample (ideally on the same block that was used for genomic testing). Despite the correlation between the HER2-enriched molecular class and the response to anti-HER2 therapy, the final result on HER2 status in discordant cases should be based on currently approved assays after results validation.

Background. Breast cancer is one of the most common female malignancies. Molecular diagnostic methods of tumor profiling allow us to analyze individual tumor characteristics, identify new prognostic and predictive markers. Aim. To increase the efficacy of systemic therapy for breast cancer and reduce inappropriate prescriptions using the data on individual molecular tumor characteristics; to develop a polygenic panel to ensure a tailored approach to systemic therapy for breast cancer. Materials and methods. We analyzed 84 tumor tissue samples from pre- and postmenopausal women with metastatic breast cancer who were treated and followed-up in 6 healthcare institutions. We assessed expression of genes involved in breast cancer. In a pilot study, we analyzed archived paraffin-embedded tumor specimens form 12 out of 1,216 patients with T1–2N0M0 breast cancer included into retrospective analysis. Gene expression was assessed using the nCounter technology based on direct digital detection of targets using fluorescent barcodes (nCounter Analysis System; NanoString Technologies, USA). Tumor tissue (biopsy and surgical specimens) was analyzed. The choice of genes was based on the literature data and experience in the development of other polygenic panels, as well as clinical significance of markers of prognostic scales. Gene mutations were confirmed by next generation sequencing and reverse transcription-polymerase chain reaction. Results. We analyzed the expression of 28 genes with a high predictive value that have been substantially studied (including ESR1, PGR, PIK3CA, BCAR4, BCAS2, CCND1, CCND2, CCND3, FOXA1, Erb2, EGFR, CDH3, FOXC1, KRT14, KRT5, CD274, CDK4, CDK6, P53, PTEN, BRCA1, BRCA2, CHEK2, CLDN3, CLDN7, AR, TOP2a, TUBBIII). We identified 29 cases of discrepancy (29 / 84; 34.5 %) in tumor subtype, including 11 cases of luminal A and B breast cancer, which might potentially affect the choice of the treatment regimen. In 18 cases, there were some principal discrepancies in the tumor subtype that implied totally different treatment regimens. The proposed polygenic signature allows accurate identification of the tumor subtype in patients with metastatic breast cancer and choice of an optimal treatment strategy. Conclusion. We have developed a 100-gene signature including molecular subtypes of breast cancer (luminal A, luminal B, basal, claudin-like) and treatment-oriented clusters. Molecular tumor profiling using this polygenic signature is an accurate method for determining tumor subtype in patients with breast cancer, which enables a tailored approach to therapy.

As a consequence of the advances in systemic neoadjuvant therapy of breast cancer is the de-escalation of surgical treatment. The study of a limited number of axillary lymph nodes after neoadjuvant therapy and refusal of lymphadenectomy in the absence of metastatic lesions is becoming more common. The published studies have proven the informativeness and safety of standard techniques of sentinel lymph node biopsy after neoadjuvant treatment for cN0 patients. For group cN1 and regression of metastases after neoadjuvant treatment, standard sentinel lymph node biopsy techniques have failed. The use of combined methods of double detection and an increase in the number of examined lymph nodes to 3 and more increased the detection rate of sentinel node biopsy after neoadjuvant therapy and reduced false-negative rate. Long-term results, questions of methodology lymph nodes evaluation, radiation therapy in this group of patients require further investigation.

Interest in adjuvant endocrine therapy in the treatment of women with breast cancer does not fade for many years. In recent decades, more and more attention has been paid to the role of ovarian suppression. Recent publications and data from international congresses confirm the necessity of prescribing predominantly medicamentous ovarian suppression to women with breast cancer and preserved menstrual function not only as a therapy but also for fertility preservation.

The article presents a literature review on late radiation injury (RI) of skin and subcutaneous fat after surgical treatment and radiation therapy (RT) in patients with breast cancer (BC). In Russia, the rate of radiation injuries in patients after RT exceeds 10–15 %. Combination treatment of BC (surgery and radiation) carries a risk of RI of skin and subcutaneous fat which might lead to dystrophic changes in the form of prominent radiation-induced fibrosis of the irradiated area, lower the quality of life, cause suffering and even death. Most of BC patients are of working age, so the problem of local RI is of social importance, and it requires effective methods of treatment and rehabilitation allowing for favorable conditions for patients’ social adaptation. Currently, there’s no consensus on the mechanisms of development of skin and subcutaneous fat late RI, and it’s being considered from several angles. Therefore, problems of determination of individual sensitivity to ionizing radiation and further study of local RI of skin and subcutaneous fat after surgical treatment and RT in BC patients are of utmost importance.

In 11.5 % of breast cancer patients distant metastases are detected at diagnosis. The results of treatment of 608 patients of 5 Russian oncological centers are presented. Removal of the primary tumor in case of newly diagnosed advanced breast cancer increases the mean duration of life from 23 up to 35 months (p < 0.01). Three-year overall survival increases from 47 to 65 % and 5-year survival – from 21 to 45 % (p = 0.001). The most impressive effect of surgical treatment is observed in patients with bone metastases, 1–2 metastatic lesions in one anatomical region, with positive effect after systemic treatment, high expression estrogen/progesterone receptors, possibility of attaining free surgical margins.

The present study aimed to investigate the immunohistochemical characteristics of the bladder (UB) of rats with infravesical obstruction (IVO) after intraperitoneal administration of biologically active compositions (BACs) (conditioned media (CM) of native and cryopreserved cultures of mantle gliocytes (MG) obtained from the spinal ganglia (SG). Methods. IVO was reproduced by surgical ligation. BACs were intraperitoneally injected for 10 days. The relative area of expression of S100 protein and actin, as markers of bladder nerve and smooth muscle cells, was calculated. The experimental animals were divided into groups as follows: 1 - intact control (n=15); 2 - CM from the culture of native MG (n=7); 3 - CM from the culture of cryopreserved MG (n=6); 4 - animals with IVO without treatment (n=15). Results. BACs obtained from the culture of native and cryopreserved MG were involved in the remodeling of the bladder structure, which changed during IVO. Visual assessment of the UB tissue specimens subjected to immunohistochemical labelling with antibodies to S100 protein and actin revealed an increase in the relative area of positive labelling in animals of groups 2 and 3 compared to group 4 (untreated). Statistical analysis demonstrated an increase in the relative area of expression of the studied markers of nervous and muscle structures by both indicators in animals of group 2 by 91.6% and 78.9% (p = 0.004; p = 0.002, respectively) compared to group 4 (without treatment). A somewhat different trend was observed when comparing the results of group 3. A statistically insignificant increase in the relative area of S100 protein expression in the UB tissues (p>0.05) and a significantly higher expression of actin by 78.8% (p=0.001) were found compared to the untreated group. Conclusions. The positive effect of neurotrophic factors contained in the secretions of native/cryopreserved SG cell cultures on the expression of immunohistochemical markers of nerve and smooth muscle cells of the bladder in the course of IVO in rats has been found. It has been determined that cryopreservation affects the nature of the biological activity of the secretions of SG cell culture. At the same time, the administration of CM of cryopreserved culture has been proven to be effective in correcting the effects of IVO and similar to the effect of CM of native culture.

The relevance of the research topic is due to the need for improvement and further development of scientific and methodological support for portfolio management processes in the context of the introduction of portfolio-oriented management in the field of local (territorial) self-government project management, including public participation (PP) projects.

At the first stage of studying the pharmacological properties of substances, the general cytotoxic effect is determined based on the assessment of viability, morphological integrity and functional activity of cells. One of the standard cell lines often used in cytotoxicity tests is the L929 line. Studying the ability of a combined lipid-lowering agent based on dense carrot root extract and quercetin to influence the morphological and functional properties of fibroblasts of the L929 line in cell culture was the aim of this study. Materials and methods. Determination of the cytotoxicity of the drug under study was carried out in a cell culture of the L929 line at a concentration of 40, 100, and 200 mg/ml. The safety of cells in the resulting suspension was assessed using staining with a 0.4 % trypan blue solution. Cell morphology and nuclear-cytoplasmic ratio were assessed in fixed culture preparations stained with hematoxylin-eosin. To assess the migration and proliferative activity of a monolayer culture, the "scratch" test was used. Results. When L929 cells were incubated in a nutrient medium with the addition of the product, their viability and morphological properties were preserved; images of a monolayer of the culture of these cells under phase-contrast microscopy coincided with the quantitative analysis data. The absence of changes in the nuclear-cytoplasmic ratio was further evidence of the absence of toxic effects of the studied drug in relation to fibroblast culture. According to the experiment results, the migration and proliferative activity of L929 cells under the influence of the drug did not differ significantly from intact cells. Conclusions. The results of the toxicological study showed that the combined product based on dense carrot root extract and quercetin does not have a cytotoxic effect on the L929 cell line culture and can be recommended for further preclinical research. [ABSTRACT FROM AUTHOR]

From analogue as philosophical and logical and gnoseological essence up to its essence and structure as a method and result of the scientific and educational cognition that identifies the interactions of different systems, phenomena, objects. This is the conception idea and the intention of the author to open the leading gnoseological role and the place of analogy among other prognostic methods of experimental pedagogy and psychology. Analogy as the general scientific method under the certain conditions is able to interfere in the well-organized heuristic activity such methods as modelling, thoughtful experiment, retrospection, intuition and others. This is a topic of out discussion in the article.

Background. The main clinical manifestations of thyroid gland (TG) diseases are associated with the influence of thyroid hormones on the cardiovascular system. At the same time, hypothyroidism as well as hyperthyroidism increase the risk of arterial hypertension. Based on this, the development of an experimental model that combines thyroid pathology and hypertension is relevant. From this point of view, the hypertensive SHR rats is a valuable object of study, since the course of arterial hypertension in these animals corresponds to the signs of human hypertension. Objective. Study of the dynamics of the morphological parameters of the thyroid gland in SHR rats with prolonged administration of propylthiouracil (PTU). Methods. Female SHR rats were used in the experiments; drinking water contained a 0.1% solution of PTU. TG was taken on the 17th, 25th, 31st, 39th and 47th days of the experiment, subjected to histological examination and staining with hematoxylin / eosin according to standard methods. We analyzed the average height of the follicular epithelium, the average follicle area, the nuclear cytoplasmic ratio (NCR) of thyrocytes, the ratio of the number of thyrocytes to fibroblasts per 50 μm2 (T/FB). Results. It was established that the height of the epithelium, NCR, and the area of the follicles change irregularly during the intake of PTU: at first, fluctuations of indicators are observed, and starting from 31st day they are stabilized. In general, after 47 days of receiving PTU, the average height of the follicular epithelium increased by 0.7 μm, the average area of the follicles – by 182 μm2, and NCR – by 0.11. In the stroma of the gland, activation of fibroblast proliferation was observed as evidenced by a decrease in the T/FB ratio from 2.87 to 0.54. Conclusion. When using a solution for drinking with 0.1% PTU for 47 days characteristic changes of hypertrophy and hyperplasia are observed in the thyroid tissue of hypertensive SHR rats. Stabilization of morphological parameters is observed after 30 days of taking PTU.

The comparative study of the functional and metabolic potentials of fibroblasts of cell line L 929 under conditions of the monolayer (2D) and threedimensional cultivations is performed. It is found that the method of cultivation of fibroblasts affects their viability and proliferative potential. In particular, it is shown that, after the volumetric cultivation of fibroblasts during 7 days, the number of viable cells and their proliferative potential significantly (p < 0.05) exceed similar indicators after the monolayer cultivation. According to data of the gel permeation chromatography, we established significant differences (p < 0.05) in the quantitative and qualitative compositions of proteinpeptide substances in cell culture media in 2D and 3D formats. Special attention is attracted by the results on the difference in the amounts of peptides in the range of molecular masses (705—1607 Da) in the medium of volumetric cultivation, which may be due to the active synthesis of growth factors. The results obtained indicate that the volumetric cultivation has a significant impact on the synthetic and morphofunctional indicators of fibroblasts of the cell line L 929 in comparison with the 2D format.

Встановлено, що на території України, зокрема і Львівської обл., горіх грецький відзначається великою формовою різноманітністю. Це дає змогу розгортати селекційні роботи з відбору та розведення кращих його форм за наповненням, величиною плодів горіха та смаковими якостями насіння. Враховуючи потреби та можливості реалізації горіхів шляхом експорту, передбачено створення спеціальних плантацій висаджуванням щеплених саджанців і перейти на отримання насіння кращих сортів горіха грецького. Інвентаризаційні роботи доцільно продовжити як на території області, так і в суміжних областях з метою створення архіву клонів кращих його сортів. Це дасть змогу ввійти до переліку провідних країн за вирощуванням насіння горіха грецького.

Using ultrasound data and content of gonadotropin and sex hormones in the blood, the morphological and functional state of the mammary glands, the uterus and the ovaries were studied in women after thyroidectomy and radioiodine therapy, who were taken suppressive therapy with levothyroxine drugs that allows to estimate the hormonal supply of the menstrual cycle and the state of reproductive system. The signs of menstrual cycle disorders and luteal phase deficiency were revealed during the treatment, and dyshormonal hyperplasia of mammary glands was also diagnosed in 82.6 % of cases due to prolonged relative hyperestrogenism and hyperplastic diseases of the uterus and the ovaries, including genital endometriosis, endometrial hyperplasia, uterine myomas, were identified in 80.4 % of cases. A long-term monitoring (every 3 months) of thyroid-stimulating hormone, thyroglobulin, thyroglobulin antibodies, follicle-stimulating hormone, luteinizing hormone, prolactin, progesterone, free testosterone, estradiol levels and also the correction of cycle supply using hormonal and non-hormonal methods are needed for this category of patients.

The development of inexpensive equipment adapted for the study of a specific biological object is very important for cryobiology. In the presented work, we have proposed a simple system for microscopy utilising open‐source platform Arduino. Testing this system showed that it had sufficient sensitivity to determine the physical processes occurring in a cryopreserved sample such as intra‐ and extracellular water crystallisation and salt eutectic. Utilising this system, we investigated the mechanisms of cryoprotection and cryodamage of testis interstitial cells (ICs) in cryoprotective media, which included cryoprotective agents such as dimethyl sulphoxide (Me2SO), as well as foetal bovine serum or polymers (dextran, hydroxyethyl starch and polyethylene glycol). It was shown that a serum‐/xeno‐free medium that included 0.7 M Me2SO and 100 mg/mL dextran was able to reduce intracellular water crystallisation in cells, change the structure of extracellular ice, and reduce salt eutectic and recrystallisation. All these effects correlated with better IC survival after cryopreservation in the medium. This medium is potentially less toxic as it has lower concentrations of Me2SO compared to serum‐containing media developed for cryopreservation of testicular cells. This would pave a way for the creation of nontoxic serum‐free compositions that does not require removal before use of cryopreserved living cells for laboratory practice or in clinics. LAY DESCRIPTION: Research in the field of cryobiology involves many technics linked with the assessment of cell recovery after cooling/warming as well as quantification, identification and description of physical processes occurring in and out of the cells. These processes can affect the overall outcome of cryopreservation. Thus, the investigation of the mechanisms of cryoprotection and cryodamage is of high importance. In this work, we have developed a system for cryomicroscopy utilising open‐source platform for prototyping electronic devices and systems Arduino. The platform includes hardware and software designed to develop various projects. It also supports a programming language. The language was used to create a code to control cooling rate of the sample undergoing microscopy. The system was able to visualise the structure of the forming ice crystals, recrystallisation, salt eutectic crystallisation/melting and intracellular phase transitions. It can be utilised in combination with other approaches and techniques. The system helped us to solve specific tasks of cryobiological experimentation connected with the establishment of mechanisms of cryoprotection and cryodamage of testis interstitial cells (ICs). The microscopy data allowed us to compare different media developed for cryopreservation of testicular cells. The serum‐containing cryoprotective medium (1.4 M Me2SO and 10% foetal bowine serum) was able to suppress darkening of cell, known as 'flashing' associated with intracellular phase transitions by moderately dehydrating cells, and salt eutectic transitions during cooling/warming. However, the media contains relatively high Me2SO concentration and may be toxic. Additionally, the use of serum in the media can result in transferring infection when cryopreserved cells are used in medicine or veterinary, or lead to instability of the composition of serum‐containing media from batch to batch. In the course of the research, we have shown that using the serum‐/xeno‐free medium supplemented with 0.7 M Me2SO and 100 mg/mL Dex (0.7 Me2SO+Dex) can also reduce cell 'flashing'. The medium influenced the size and shape of extracellular ice crystals in a way that can potentially reduce the risk of mechanical cell damage. This medium promoted amorphous solidification in the space between the extracellular ice crystals, thus, lowering the salt eutectic transitions and recrystallisation that could otherwise cause additional cell damage. Therefore, application of the developed system for cryomicroscopy, which allowed real‐time visualisation of cryobiological processes, made it possible to draw a conclusion about cryoprotecitive properties of medium for ICs. 0.7 Me2SO+Dex can be the basis for the creation of commercial serum‐free media with a defined composition that does not require removal before use. [ABSTRACT FROM AUTHOR]

Досліджено, що деревина карії овальної відрізняється від інших листяних порід своєю будовою, вона містить до 56,2 % целюлози, має потовщені стінки лібриформу, що надає їй високої щільності та характеризується високими показниками фізико-механічних властивостей. Порівняно з дубом та ясенем, її щільність є вищою на 21,7 та 20,5 %. Характерною особливістю є висока та майже однакова статична твердість на трьох площинах зрізу, що відрізняє її за цим показником від інших листяних порід. За високої твердості деревина карії відзначається особливою в'язкістю, що зумовлено наявністю тяжів деревної паренхіми. Її впровадження створює передумови для заготівлі високоякісної деревини для лижного виробництва, виготовлення спортивного інвентарю, столярних інструментів, деталей сільськогосподарського машинобудування, для виготовлення гнутих виробів.

The results of calculations of possible state of water resources within The Danube River basin in the XXI century were shown. This estimation was based on the model "climate-runoff", developed in Odessa State Environmental University. As the input to model data of climate scenario A1B (model REMO) were used. Average long-term annual flow values using meteorological data (air temperature and precipitation) from the scenario for different climatic periods of XXI century were calculated. 32 points (grid nodes) which were uniformly distributed over the catchment area of the Danube River were studied. Projection of changes in water resources was given by comparing the calculation results in the past (before 1989) and in the future (1990-2030, 2031-2070, 2071-2100). The major trends in climatic factors of the flow formation and water resources were established. It is shown that the climatic conditions in the XXI century on the Danube River catchment is unfavorable for the formation of runoff. The positive component of the water balance (precipitation) remains unchanged and the negative component (evaporation) increases. Isolines of norms of climatic annual flow within the whole basin were constructed. It is established that by 2030 a significant reduction of water resources will not occur; during the 2031-2070 diminution will be 17,9 %; during the 2071-2100 – 22,0 %.

Data of climate change scenarios RCP8.5 and RCP4.5 (Representative Concentration Pathways) were used. They were proposed for consideration in the Fifth Report of Intergovernmental Panel on Climate Change. Average long-term annual flow values using meteorological data (air temperature and precipitation) from the scenarios for the period 2011-2050 were calculated. 84 points (grid nodes) uniformly distributed on the territory of Ukraine were studied. The calculations were made based on the model "climate-runoff", developed in Odessa State Environmental University. Projection of changes in water resources was given by comparing the calculation results in the past (before 1989) and in the future (2011-2050). The major trends in water resources of Ukraine were established. It is shown that by the middle of the XXI century reducing of water resources is expected on the plain territory of Ukraine (70% in the southeast). In the geographical zone of the Ukrainian Carpathians, especially in the Tisa river basin, its stability or growth is possible. Analysis of changes in the ratio of moisture and heat resources showed that climate aridity will be intensify and the insufficient moisture zone and the semiarid zone will be widen.

Background: Schlemm’s canal collaps and increased trabecular (especially juxtacalanicular) resistance play an important role in the development of glaucoma. Dilation of Schlemm’s canal and moderate trabecular extension promote restoration of natural aqueous outflow pathways. Previously we had developed first generation Schlemm’s canal expander (SKE-1) and proved its efficacy in decreasing intraocular pressure in open-angle glaucoma. Though, inappropriate size of the expander results in traumatic implantation. Thus, we developed second generation Schlemm’s canal expander (SKE-2) characterized by smaller length and diameter. Aim: To evaluate effectiveness of SKE-2 in decreasing intraocular pressure in open-angle glaucoma. Materials and methods: 25 patients (25 eye) were included. 13 patients (13 eyes) in the intervention group underwent glaucoma surgery with SKE-2 implantation. The results were compared with SKE-1 implantation in the control group (12 patients, 12 eyes). The groups were age-, sex and glaucoma stage-matched (p > 0.05). The patients were followed for 1 year. Outcome measures included intraocular pressure changes, complication rate, need for additional hypotensive therapies and repeat surgery. Results: Intraocular pressure changes, need for additional hypotensive therapies frequency of intra- and postoperative complications didn’t differ between the groups. Trabeculopuncture with yttrium aluminum garnet (YAG) laser as a second step procedure was needed in 2 cases (16%) in the control group and in 5 cases (38%) in the intervention group (p = 0.002). Conclusion: SKE-1 and SKE-2 are equally effective in reducing intraocular pressure in open-angle glaucoma. Though, after SKE-2 implantation, YAG laser goniopuncture is more frequently needed as a second step procedure.