УРОВЕНЬ ГОРМОНОВ В ТКАНИ РАКА ТЕЛА МАТКИ И ИНТАКТНЫХ ЯИЧНИКАХ АССОЦИИРОВАННЫЙ С РАЗЛИЧНЫМИ ВИРУСНЫМИ ИНФЕКЦИЯМИ

Oncogenic impact of transformative viruses on the risk of cancer is well known. Today there are no studies focused on the effect of widespread, often persisting infections, such as herpes simplex virus (HSV), cytomegalovirus (CMV) and chlamydial infections on the level of hormones in the reproductive organs and their role in the pathogenesis of endometrial cancer.  The aim of this study is to evaluate the effect of infectious agents in the substantive and concomitant conditions on the local hormone production in tissue of uterus and ovaries in patients with cancer of the body of uterus in menopausal age.In the tumor, in perifocal zone and in unaltered ovaries in patients with cancer of the body of uterus ELISA and PCR method determines the presence of herpes simplex virus types 1 and 2, cytomegalovirus and chlamydial infection. Depending on the level of infection in the tissues the local level of saturation of sex hormones, sex hormone binding globulin, prolactin were evaluated in samples of endometrium and ovaries. The presence of infectious agents have a modifying effect on local hormone production, increasing the intensity of disorders resulting in an imbalance of steroids, estrogen metabolites disturbance ratio and strengthening prolactinemia not only in tumor tissue but also in unchanged ovaries in patients  with cancer of the body of uterus.Известно онкогенное влияние трансформирующих вирусов на риск развития онкологических заболеваний.  Практически не исследовано влияние широко распространенных,  зачастую персистирующих инфекций, типа вируса простого герпес  (ВПГ), цитомегаловируса  (ЦМВ) и хламидийных инфекций на гормональный фон в органах репродуктивной системы и роль их в патогенезе рака тела матки. Целью работы явилось изучение влияния инфекционных агентов в самостоятельном и сочетанных вариантах на локальный гормоногенез  тканей матки и яичников у больных раком тела матки менопаузального  возраста.  В опухоли, перифокальной  зоне и неизмененных  яичниках у больных раком  тела матки ИФАи ПЦР методами определяли наличие вируса простого герпеса 1-го и 2-го типов, цитомегаловирусную и хламидийную инфекции. В зависимости  от инфицированности тканей изучали уровень локальной насыщенности образцов  эндометрия  и яичников половыми гормонами, секстероидсвязывающим  глобулином, пролактином. Присутствие инфекционных агентов оказывает модифицирующее влияние на локальный гормоногенез,  увеличивая интенсивность нарушений, что приводит к дисбалансу стероидов,  нарушению соотношения метаболитов эстрогенов и усилению пролактинемии не только в опухолевой ткани, но и в неизмененных  яичниках у больных раком тела матки

Teaching Reading Digital Texts within Neuroscientific Achievements

The authors consider the process of teaching learners reading digital texts as pedagogical support for their search activity. Taking into account psychophysiological regularities and psychological mechanisms a teacher gets an opportunity to simulate the environment and conditions for learners to form implications, formulate questions and implement research and search for new questions based on the obtained results with the help of hypertextuality, multimedia and interactivity of digital texts in a real educational process. The purpose of the study is to identify a strategy for reading digital text. The simulation experiment for senior learners includes two opposite ways of teaching reading digital text. He/she had to start first with the short text reading, then with the corresponding picture and vice versa. The personal significance of the read text or picture, understanding of the text content and the accuracy of its reproduction were taken into account. Experimental evidence suggests the importance of using strategies for teaching reading a digital text as strategies allow the learner to act as a subject of attitude to the subject of knowledge. Teacher’s digital text-based sequencing of learning situations, based on the principle of integrity, provides a sequence of future-oriented behavioral acts in the context of neuroscience achievements

Evaluation of Toxic Properties of New Glycopeptide Flavancin on Rats

Glycopeptide antibiotics have side effects that limit their clinical use. In view of this, the development of glycopeptides with improved chemotherapeutic properties remains the main direction in the search for new antibacterial drugs. The objective of this study was to evaluate the toxicological characteristics of new semi-synthetic glycopeptide flavancin. Acute and chronic toxicity of antibiotic was evaluated in Wistar rats. The medium lethal dose (LD50) and the maximum tolerated doses (MTD) were calculated by the method of Litchfield and Wilcoxon. In the chronic toxicity study, the treatment regimen consisted of 15 daily intraperitoneal injections using two dosage levels: 6 and 10 mg/kg/day. Total doses were equivalent to MTD or LD50 of flavancin, respectively. The study included assessment of the body weight, hematological parameters, blood biochemical parameters, urinalysis, and pathomorphological evaluation of the internal organs. The results of the study demonstrated that no clinical-laboratory signs of toxicity were found after 15 daily injections of flavancin at a total dose close to the MTD or LD50. The pathomorphological study did not reveal any lesions on the organ structure of animals after low-dose administration of flavancin. Thus, flavancin favorably differs in terms of toxicological properties from the glycopeptides currently used in the clinic

DataSheet1_Mechanism of curaxin-dependent nucleosome unfolding by FACT.pdf

Human FACT (FACT) is a multifunctional histone chaperone involved in transcription, replication and DNA repair. Curaxins are anticancer compounds that induce FACT-dependent nucleosome unfolding and trapping of FACT in the chromatin of cancer cells (c-trapping) through an unknown molecular mechanism. Here, we analyzed the effects of curaxin CBL0137 on nucleosome unfolding by FACT using spFRET and electron microscopy. By itself, FACT adopted multiple conformations, including a novel, compact, four-domain state in which the previously unresolved NTD of the SPT16 subunit of FACT was localized, apparently stabilizing a compact configuration. Multiple, primarily open conformations of FACT-nucleosome complexes were observed during curaxin-supported nucleosome unfolding. The obtained models of intermediates suggest “decision points” in the unfolding/folding pathway where FACT can either promote disassembly or assembly of nucleosomes, with the outcome possibly being influenced by additional factors. The data suggest novel mechanisms of nucleosome unfolding by FACT and c-trapping by curaxins.</p

Volumetric modulated arc therapy with flattening filter free beams for isolated abdominal/pelvic lymph nodes: report of dosimetric and early clinical results in oligometastatic patients

<p>Abstract</p> <p>Background</p> <p>SBRT is a safe and efficient strategy to locally control multiple metastatic sites. While research in the physics domain for Flattening Filter Free Beams (FFF) beams is increasing, there are few clinical data of FFF beams in clinical practice. Here we reported dosimentric and early clinical data of SBRT and FFF delivery in isolated lymph node oligometastatic patients.</p> <p>Methods</p> <p>Between October 2010 and March 2012, 34 patients were treated with SBRT for oligometastatic lymph node metastasis on a Varian TrueBeam^TM treatment machine using Volumetric Modulated Arc Therapy (RapidArc). We retrospectively evaluated a total of 25 patients for isolated lymph node metastases in abdomen and/or pelvis treated with SBRT and FFF (28 treatments). Acute toxicity was recorded. Local control evaluation was scored by means of CT scan and/or PET scan.</p> <p>Results</p> <p>All dosimetric results are in line with what published for the same type of stereotactic abdominal lymph node metastases treatments and fractionation, using RapidArc. All 25 FFF SBRT patients completed the treatment. Acute gastrointestinal toxicity was minimal: one patient showed Grade 1 gastrointestinal toxicity. Three other patients presented Grade 2 toxicity. No Grade 3 or higher was recorded. All toxicities were recovered within one week. The preliminary clinical results at the median follow up of 195 days are: complete response in 12 cases, partial response in 11, stable disease in 5, with an overall response rate of 82%; no local progression was recorded.</p> <p>Conclusions</p> <p>Data of dosimetrical findings and acute toxicity are excellent for patients treated with SBRT with VMAT using FFF beams. Preliminary clinical results showed a high rate of local control in irradiated lesion. Further data and longer follow up are needed to assess late toxicity and definitive clinical outcomes.</p

Recent progress in L-H transition studies at JET: Tritium, Helium, Hydrogen and Deuterium

We present an overview of results from a series of L-II transition experiments undertaken at JET since the installation of the ITER-like-wall (JET-ILW), with beryllium wall tiles and a tungsten divertor. Tritium, helium and deuterium plasmas have been investigated. Initial results in tritium show ohmic L-H transitions at low density and the power threshold for the L-H transition (P-LH) is lower in tritium plasmas than in deuterium ones at low densities, while we still lack contrasted data to provide a scaling at high densities. In helium plasmas there is a notable shift of the density at which the power threshold is minimum ((n) over bar (e,min)) to higher values relative to deuterium and hydrogen references. Above (n) over bar (e,min) (He) the L-H power threshold at high densities is similar for D and He plasmas. Transport modelling in slab geometry shows that in helium neoclassical transport competes with interchange-driven transport, unlike in hydrogen isotopes. Measurements of the radial electric field in deuterium plasmas show that E-r shear is not a good indicator of proximity to the L-H transition. Transport analysis of ion heat flux in deuterium plasmas show a non-linearity as density is decreased below (n) over bar (e,min). Lastly, a regression of the JET-ILW deuterium data is compared to the 2008 ITPA scaling law

Genomic Classification of Cutaneous Melanoma

We describe the landscape of genomic alterations in cutaneous melanomas through DNA, RNA, and protein-based analysis of 333 primary and/or metastatic melanomas from 331 patients. We establish a framework for genomic classification into one of four sub-types based on the pattern of the most prevalent significantly mutated genes: mutant BRAF, mutant RAS, mutant NF1, and Triple-WT (wild-type). Integrative analysis reveals enrichment of KIT mutations and focal amplifications and complex structural rearrangements as a feature of the Triple-WT subtype. We found no significant outcome correlation with genomic classification, but samples assigned a transcriptomic subclass enriched for immune gene expression associated with lymphocyte infiltrate on pathology review and high LCK protein expression, a T cell marker, were associated with improved patient survival. This clinicopathological and multidimensional analysis suggests that the prognosis of melanoma patients with regional metastases is influenced by tumor stroma immunobiology, offering insights to further personalize therapeutic decision-makingclose3