Concurrent thermochemoradiotherapy for brain high-grade glioma

Despite the achievements in the current strategies for treatment, the prognosis in malignant glioma patients remains unsatisfactory. Hyperthermia is currently considered to be the most effective and universal modifier of radiotherapy and chemotherapy. Preliminary treatment outcomes for 28 patients with newly diagnosed (23) and recurrent (5) high-grade gliomas were presented. All the patients received multimodality treatment including surgery, thermoche-moradiotherapy followed by 4 cycles of adjuvant chemotherapy. All the patients endured thermochemoradiotherapy well. A complication, limited skin burn (II stage), was diagnosed in two cases and treated conservatively without treatment interruption. A month after thermochemoradiotherapy the results were as follows: complete regression was achieved in 4 cases, partial regression in 4 cases, stable disease in 14 cases and disease progression in 6 cases (one of them is pseudo-progression). After completing the adjuvant chemotherapy 2 more patients demonstrated complete response and 1 patient had disease progression. Introduction of local hyperthermia in multimodal therapy of malignant glioma does not impair the combined modality treatment tolerability of patients with malignant gliomas. A small number of studied patients and short follow-up time do not allow making reliable conclusions about the impact of local hyperthermia on the treatment outcomes; however, there is a tendency towards the increase in disease-free survival in the patients with newly diagnosed malignant gliomas

Критерий оценки экологического состояния донных отложний (на примере Брестской области)

Geochemical parameters of bottom sediments allow quick estimating the state of the environment within the catchment of watercourses, as the composition of bottom sediments inherits the geochemical features of the components of the surrounding landscape. New data on the content of trace elements, sulfates, chlorides, nitrates, petroleum products, synthetic surfactants and phenols in the bottom sediments, obtained during complex geochemical studies in the Brest region, are presented. The concentration levels of the determined ingredients for sediments of the main types of reservoirs were determined. The maximum accumulation of nitrogen compounds, chlorides, phosphates and trace elements (nickel, cobalt, vanadium, chromium, copper, zinc and manganese) was marked in the sediments of rivers, while sulfates and lead are concentrated to a greater extent in the bottom sediments of the drainage channels. The map of pollution of bottom deposits of the territory of the Brest region of scale 1:200000 was constructed. It was found that the geochemical state of bottom sediments in the reservoirs of the Brest region is mainly in satisfactory condition, the degree of pollution by heavy metals was estimated as permissible with only 3.0 % belonging to the category of dangerous pollution level.Необходимость проведения геохимических исследований донных отложений обусловлена тем, что они позволяют оперативно оценивать состояние окружающей среды в пределах водосбора водотоков, так как состав донных отложений наследует геохимические черты компонентов окружающего ландшафта. В работе впервые представлены новые данные по содержанию в донных отложениях микроэлементов, сульфатов, хлоридов, нитратов, нефтепродуктов, СПАВ и фенолов, полученные при комплексных геохимических исследованиях в Брестской области. Установлены уровни концентраций определяемых ингредиентов для отложений основных типов водоемов. Отмечено максимальное накопление соединений азота, хлоридов, фосфатов и микроэлементов (никеля, кобальта, ванадия, хрома, меди, цинка и марганца) в отложениях рек, сульфаты и свинец концентрируются в большей степени в донных отложениях мелиоративных каналов. Построена карта загрязнения донных отложений территории Брестской области масштаба 1:200000. Установлено, что геохимическое состояние донных отложений в водоемах Брестской области находится в основном в удовлетворительном состоянии, степень загрязненности тяжелыми металлами оценивается как допустимая и только 3,0 % попадает в категорию опасного уровня загрязнения

Характеристика загрязнений почвенного покрова Припятского Полесья в Брестской области

The geochemical condition of soils in Pripyat' Polesye, Brest region, has been studied. The main sources of soil pollution by chemicals have been determined and maps for their distribution have been drawn. Areas of soils polluted by nitrates, sulphates, chlorides and heavy metals have been calculated.Изучено геохимическое состояние почвенного покрова Припятского Полесья в Брестской области. Установлены основные источники загрязнений почв химическими соединениями и составлены карты-схемы пространственного их распределения. Рассчитаны площади загрязнения почв нитратами, сульфатами, хлоридами и тяжелыми металлами

Concurrent Thermochemoradiotherapy in Glioblastoma Treatment: Preliminary Results

Glioblastoma is the most frequent and aggressive primary brain tumor. The patient can be alive with this pathology using the modern standard of intensive combined treatment less than 2 years. Between December 2013 and August 2017, 30 patients with newly diagnosed supratentorial glioblastoma had received concomitant chemoradiotherapy with transcranial radiofrequency hyperthermia. The gross total or the subtotal resection of the tumor was made previously in all cases. The median follow-up time after operation achieved 12 months (95% confidence interval (CI): 8.5–23 months) in this study. The median disease-free survival time was 9.6 months (95% CI: 7.2–19.0 months). The median overall survival time of patients included in the study was 23.4 months. No increase in the systemic side effects of chemotherapy was found compared with the frequency described in the population. Preliminary results had shown that the usage of concomitant thermochemoradiotherapy with transcranial radiofrequency hyperthermia improves progression-free survival rates. Overall survival rates also tended to increase. Given the absence of severe complications, it is necessary to continue research to achieve statistically significant results

Detection of highly conductive surface electron states in topological crystalline insulators Pb1−xSnxSe using laser terahertz radiation

We suggest a method for detection of highly conductive surface electron states including topological ones. The method is based on measurements of the photoelectromagnetic effect using terahertz laser pulses. In contrast to conventional transport measurements, the method is not sensitive to the bulk conductivity. The method is demonstrated on an example of topological crystalline insulators Pb1−xSnxSe. It is shown that highly conductive surface electron states are present in Pb1−xSnxSe both in the inverse and direct electron energy spectrum

Seroprevalence of sars-cov-2 antibodies in symptomatic individuals is higher than in persons who are at increased risk exposure: The results of the single-center, prospective, cross-sectional study

The present study aimed to assess antibody seropositivity prevalence among symptomatic individuals and individuals with a high risk of occupational exposure to SARS-CoV-2. Participants from Chelyabinsk (Russian Federation) who were at an increased risk of exposure to SARS-CoV-2 (high-risk group, n = 1091) and participants who either had symptoms consistent with COVID-19 or were suspected to have experienced COVID-19 in the past (symptomatic group, n = 692) were enrolled between 28 September and 30 December 2020. Blood samples were tested by enzyme-linked immunosorbent assay D-5501 SARS-Cov-2-IgG-EIA-BEST and D-5502 SARS-Cov-2-IgM-EIA-BEST (AO Vector-Best, Novosibirsk, Russia). The overall seropositivity rate was 28.33–28.53%. SARS-CoV-2 antibodies were detected in 17.23% (adjusted prevalence of 17.17–17.29%) of participants in the high-risk and 45.95% (adjusted prevalence of 45.91–46.24%) in the symptomatic group. Higher IgG and IgM titers were observed in women compared to men, as well as in participants in the symptomatic group compared to those in the high-risk group. The results indicate that the seroprevalence among residents in several Russian regions is low (28.38%) and inadequate to provide herd immunity. The lower seroprevalence among participants in the high-risk group may be attributed to the enforcement of healthcare protocols and the use of adequate personal protective equipment. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.The reported study was funded by RFBR and NSFC (project No.20-515-55003), by the NSFC (project No. 82161138003), and partly by the Government contract of the Institute of Immunology and Physiology (AAAA-A21-121012090090-9)

Human APP Gene Expression Alters Active Zone Distribution and Spontaneous Neurotransmitter Release at the Drosophila Larval Neuromuscular Junction

This study provides further insight into the molecular mechanisms that control neurotransmitter release. Experiments were performed on larval neuromuscular junctions of transgenic Drosophila melanogaster lines with different levels of human amyloid precursor protein (APP) production. To express human genes in motor neurons of Drosophila, the UAS-GAL4 system was used. Human APP gene expression increased the number of synaptic boutons per neuromuscular junction. The total number of active zones, detected by Bruchpilot protein puncta distribution, remained unchanged; however, the average number of active zones per bouton decreased. These disturbances were accompanied by a decrease in frequency of miniature excitatory junction potentials without alteration in random nature of spontaneous quantal release. Similar structural and functional changes were observed with co-overexpression of human APP and β-secretase genes. In Drosophila line with expression of human amyloid-β42 peptide itself, parameters analyzed did not differ from controls, suggesting the specificity of APP effects.These results confirm the involvement of APP in synaptogenesis and provide evidence to suggest that human APP overexpression specifically disturbs the structural and functional organization of active zone and results in altered Bruchpilot distribution and lowered probability of spontaneous neurotransmitter release

"Apparent PT-symmetric terahertz photoconductivity in the topological phase of Hg1−xCdxTe-based structures"

We show that the terahertz (THz) photoconductivity in the topological phase of Hg1-xCdxTe-based structures exhibits the apparent PT- (parity-time) symmetry whereas the P-symmetry and the T-symmetry, separately, are not conserved. Moreover, it is demonstrated that the P- and T-symmetry breaking may not be related to any type of the sample anisotropy. This result contradicts the apparent symmetry arguments and means that there exists an external factor that interacts with the sample electronic system and breaks the symmetry. We show that deviations from the ideal experimental geometry may not be such a factor

Роль галектина-1, -3 в механизмах дисрегуляции Т-клеточного звена иммунного ответа при раке толстого кишечника

The aim of the study was to characterize the features of the subpopulation composition and cytokine-secretory activity of T lymphocytes (Th1, Th17 and Treg) in relation to the concentration of galectin-1 and galectin-3 in the blood of patients with colon cancer.Materials and methods. A total of 26 patients diagnosed with colon cancer were examined. The study material included whole peripheral blood, blood plasma, and supernatants of suspension cultures of mononuclear leukocytes. Lymphocytes isolated from blood were typed by flow cytometry using monoclonal  antibodies. The content of galectin-1 and galectin-3 (in blood plasma) and IFNγ, IL-17A, and TGFβ (in supernatants of mononuclear leukocyte culture in vitro) were determined by enzyme-linked immunosorbent assay. The results obtained were analyzed by statistical methods.Results. In patients with colon cancer, a significant increase in the concentration of galectin-1 and galectin-3 in the blood plasma was found, which was associated with a decrease in the content of CD4+T-bet+ Th1 lymphocytes, CD4+RORC2+ Th17 lymphocytes in the blood and in vitro hyposecretion of IL-17. At the same time, positive correlations were revealed between the concentration of galectin-1 and galectin-3, the content of CD4+FoxP3+ Treg cells in the blood, and the secretion of TGFβ by mononuclear leukocytes in vitro.Conclusion. In colon cancer, increased levels of galectin-1 and galectin-3 in the blood are associated with quantitative deficiency and inhibited secretory activity of effector T lymphocytes and activation of the immunosuppressive functions of regulatory T cells. These results suggest a negative role of galectin 1 and galectin 3 in the mechanisms of regulation of the T cell immune response in colon cancer.Цель исследования – охарактеризовать особенности субпопуляционного состава и цитокин-секреторной активности Т-лимфоцитов (Th1, Th17 и Treg) во взаимосвязи с концентрацией галектина-1 и галектина-3 в крови у больных раком толстого кишечника.Материалы и методы. Обследованы 26 пациентов (14 мужчин и 12 женщин, средний возраст (62,9 ± 6,7) лет) с диагнозом рака толстого кишечника. В группу контроля вошли 17 здоровых доноров (11 мужчин и 6 женщин, средний возраст (58,2 ± 3,1) лет). Материалом исследования служила цельная периферическая кровь, плазма крови и супернатанты суспензионной культуры мононуклеарных лейкоцитов. Выделенные из крови лимфоциты типировали методом проточной лазерной цитофлуориметрии с использованием моноклональных антител. Методом иммуноферментного анализа определяли содержание галектина-1 и галектина-3 (в плазме крови) и IFNγ, IL-17A и TGFβ (в супернатантах культуры мононуклеарных лейкоцитов in vitro). Полученные результаты анализировали статистическими методами.Результаты. У больных раком толстого кишечника установлено значимое увеличение концентрации галектина-1 и галектина-3 в плазме крови, ассоциированное со снижением содержания CD4+T-bet+ Th1- лимфоцитов, CD4+RORC2+ Th17-лимфоцитов в крови и гипосекрецией IL-17 лимфоцитами in vitro. Напротив, выявлена положительная корреляция между концентрацией галектинов 1 и 3, содержанием CD4+FoxP3+Treg клеток в крови и секрецией TGFβ мононуклеарными лейкоцитами in vitro.Заключение. При раке толстого кишечника повышенный уровень галектинов 1 и 3 в крови сопряжен с количественным дефицитом и угнетением секреторной активности эффекторных Т-лимфоцитов, и, напротив, активацией иммуносупрессорных функций  регуляторных Т-клеток. Полученные результаты указывают на негативную роль галектина-1 и галектина-3 в механизмах регуляции Т-клеточного звена иммунного ответа при раке толстого кишечника

Molecular genetic features of the development of restrictive cardiomyopathy in Russian children

Aim. To identify the proportion of restrictive cardiomyopathy (RCM), as well as cardiomyopathy (CMP) with a restrictive type of hemodynamics among all cases of genetic CMP and to determine the relative frequencies and spectrum of nucleotide variants in Russian children with RCM, as well as to search for phenogenotypic correlations.Material and methods. The study included 689 children with CMPs. All children underwent a molecular genetic testing of the target regions of 419 genes responsible for various cardiomyopathies and channelopathies using the method of massively parallel sequencing (MPS).Results. In 668 (97,0%) children, pathogenic, likely pathogenic nucleotide variants, as well as nucleotide variants with unknown clinical significance, were identified. Of these, 45 (6,7%) patients were selected to determine the molecular genetic characteristics of RCM, 20 of whom had clinical symptoms and morphofunctional structure of RCMP (3,0%), while the remaining 25 (3,7%) children were diagnosed with another CMP type with a restrictive type of hemodynamics. In total, these patients had 41 nucleotide variants in 15 different genes, while 19 (46,3%) variants were pathogenic, 12 (29,3%) — likely pathogenic, 10 (24,4%) — uncertain clinical significance. Pathogenic and likely pathogenic variants were identified in a total of 38 (84,4%) patients, while in 19 (42,2%) patients, the pathogenic variants described earlier were found. The most common genetic marker of RCM in Russian children was TNNI3 gene mutations. In total, they were identified in 12 (25%) children: with RCP — 8 (40%) patients; with CMP with a restrictive type of hemodynamics — 4 (16%) patients. At the same time, the most common mutation of the TNNI3 gene was the nucleotide variant c.575G>A, leading to the amino acid variant p.R192H, described earlier in patients with RCM and identified by us in three (15%) unrelated children with RCM. In addition, a significant difference was found between the averaged values of N-terminal pro-brain natriuretic peptide in patients with mutations in the MYH7 and TNNI3 genes (0,0039, p<0,05), as well as between the peak flow gradient values in children with mutations in TNNI3 and FLNC genes (0,0016, p<0,05), TNNI3 and MYH7 genes (0,039, p<0,05).Conclusion. The results of this study indicate a significant genetic heterogeneity of RCM in Russian children and the need for further research aimed at finding genotype-phenotype associations in order to predict the course of the disease and select the proper therapy