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Samples taken from the human brain (Globus Pallidus) have been investigated by physical techniques such as light microscopy, scanning electron microscopy, transmission electron microscopy, Mössbauer spectroscopy and SQUID magnetometry. SEM-EDX/TEM investigation reveals multielemental composition of hematite and magnetite nanocrystals with sizes ranging from 40 nm to 100 nm and hematite microcrystals from 3 μm to 7 μm. Room temperature Mössbauer spectra show quadrupole doublets assigning to hematite and ferrihydrite. SQUID measurements of temperature dependence of the mass magnetic susceptibility between T = 2 – 300 K at DC field B0 = 0.1 T, the field dependence of the mass magnetization taken at the fixed temperature T0 = 2.0 and 4.6 K and the zero-field cooled and field cooled magnetization experiments (ZFCM/FCM) confirm a presence of ferrimagnetic phases such as maghemite and/or magnetite with hysteresis loops surviving until the room temperature. Differences between these measurements from the point of view of iron oxides detected can indicate important processes in human brain and interactions between ferritin as a physiological source of iron and surrounding environment.

The shrinking of cities is a process that accompanies cities in post-conjunctural changes, when they are entering a phase of economic decline and the decline in population connected with it. The Ostrava- Karviná area is one of the economically problematic regions in the Czech Republic nowadays but it used to be ranked as one of the economic heartlands in the period of socialism. The region, dependent on bituminous coal mining and heavy industry, gradually began to decline after the year 1989 and one of the consequences is a significant decline in its population. This paper deals with identification of the causes and consequences of shrinking cities explained through the example of the town of Karviná through an analysis of quantitative data, questionnaire surveys, and semi-structured interviews. The questionnaire survey revealed that the main reason causing the departure of young and educated citizens is the lack of work opportunities. High unemployment and thus the presence of many socially disadvantaged people causes the atmosphere in the city to deteriorate, and this is accompanied by social problems, such as ageing of the population or criminality. Lack of safety of citizens and a bad environment are other reasons why young people leave the city. The decreasing number of citizens closes the vicious circle by leading to a lower demand for services, closing of shops and other services and increasing numbers of empty houses and flats. Another essential part of the paper is the question of possible measures by the local authority leading to the elimination of these undesirable phenomena, but also the belief in the necessity of help from the government.

This paper deals with the institutional and factual readiness of cities and villages in the Czech Republic to use Integrated Territorial Investments (ITI). On the basis of a questionnaire survey carried out in May 2014 among representatives of 69 municipalities around the core cities of Brno, Jihlava, Olomouc and Hradec Králové - Pardubice as well as a comparison of several model agglomerations, it identifies the main problems and proposes solutions to them. The main theme of this paper is to evaluate the formation of partnerships of municipalities and the process of creating integrated strategies for metropolitan areas. The paper also deals with the relationships and functional links between cities and villages and their hinterland, the common development issues and the existing structures of cooperation and communication. In the conclusion possible recommendations are given to improve the ITI functioning in the Czech Republic on the basis of both, the assessment of the situation in the Republic itself and the reflection on developments in other EU countries.

In the period 2008–2010, the labour market of the European Union was significantly affected by the economic recession, which impacted economic development in all regions of the Czech Republic including the South Moravian Region. Impacts of the economic recession in the labour market were primarily reflected on decline of vacant work places, an increase in job seekers, and thus an increase in the unemployment rate, as well as an increase in long-term unemployment,etc. Enterprises in the region are responding to this situation in different ways, but all have to flexibly adapt – increase or decrease – the number of employees and production as movements in the labour market have been very significant for the past four years. In 2011 and 2012, the economic recession was not discussed anymore. However, has it already finished? The analysis of movements in the labour market, especially comparison of plans and reality in enterprises during and after economic recession is the aim of the paper.

CD8 + T cells protect against tumors and intracellular pathogens. The inflammatory cytokines IL-2, IL-15, and IL-7 are necessary for their expansion. However, elevated serum levels of these cytokines are often associated with cancer, poorer prognosis of cancer patients, and exhaustion of antigen-expanded CD8 + T cells. The impact of acute conditioning of antigen-expanded CD8 + T cells with these cytokines is unknown. Here, we generated antigen-expanded CD8 + T cells using dendritic cells and PC-3 cells. The cells were acutely (18-24 h) conditioned with IL-2 and either the GSK3β inhibitor TWS119, the mTORC1 inhibitor rapamycin, or the mTORC1/2 inhibitor Torin1, then their immediate and post-re-expansion (distal) cytokine responses after antigen rechallenge were evaluated. We found that acute IL-2 conditioning upregulated the immediate antigen-induced cytokine response of the tested cells. Following their re-expansion, however, the cells showed a decreased cytokine response. These IL-2 conditioning-mediated impacts were counteracted with TWS119 or rapamycin but not with Torin1. Our data revealed that the acute conditioning of antigen-expanded CD8 + T cells with IL-2 modulates the GSK3β-mTORC signaling axis. This modulation differentially affected the immediate and distal cytokine responses of the cells. The acute targeting of this signaling axis could, therefore, represent a novel strategy for the modulation of antigen-expanded CD8 + T cells.

Modern Holter devices are very trendy tools used in medicine, research, or sport. They monitor a variety of human physiological or pathophysiological signals. Nowadays, Holter devices have been developing very fast. New innovative products come to the market every day. They have become smaller, smarter, cheaper, have ultra-low power consumption, do not limit everyday life, and allow comfortable measurements of humans to be accomplished in a familiar and natural environment, without extreme fear from doctors. People can be informed about their health and 24/7 monitoring can sometimes easily detect specific diseases, which are normally passed during routine ambulance operation. However, there is a problem with the reliability, quality, and quantity of the collected data. In normal life, there may be a loss of signal recording, abnormal growth of artifacts, etc. At this point, there is a need for multiple sensors capturing single variables in parallel by different sensing methods to complement these methods and diminish the level of artifacts. We can also sense multiple different signals that are complementary and give us a coherent picture. In this article, we describe actual interesting multi-sensor principles on the grounds of our own long-year experiences and many experiments.

The paper presents the application of natural materials, especially wood, which are relevant for human well-being in built environments of health, social, and day care facilities. These properties were tested by a complex methodology in a case study in the wooden waiting room at National Oncology Institute in Bratislava. In this space, experimental tests of physiological responses were further executed on 50 volunteers moving in the waiting room for 20 min. In this article, the EEG (electroencephalograph) (four persons) and emotions from the faces of all our volunteers before entering and after a stay in a wooden waiting room were recorded. Specifically, the ECG (electrocardiograph), heart rate (HR), and respiration activity were measured by using our own designed ECG holter (40 persons), and also blood pressure and cortisol levels were observed. The usage of wooden materials verifies their regenerative and positive impact on the human nervous system, through the appealing aesthetics (color, texture, and structures), high contact comfort, pleasant smell, possibility to regulate air humidity, volatile organic compound emissions (VOC-emissions), and acoustic well-being in the space.

Inter-strand crosslinks (ICL) in the DNA are regarded to be the main toxic lesions induced by sulphur mustard (SM). We have followed the induction of ICL in the DNA of different organs of Wistar rats and Balb/c or NMRI mice by the percutaneous application of SM using the modified (reverse) comet assay. Significant amounts of ICL were found in Balb/C lymphocytes, in bone marrow and liver cells after the dose of 80 mg/kg. A dose-dependent amount of ICL was induced in rats, with efficient induction in lymphocytes and spleen cells already after 5 mg SM/kg, indicating a higher susceptibility of rats to the DNA-damaging effect of SM compared with mice. A significant induction of ICL in other tested tissues (liver, bone marrow, colon epithelium) was seen at the dose of 20 mg/kg. The induced ICL were removed from the DNA during 48 h except for rats at the dose of 80 mg/kg. In fact, we observed that ICL are almost completely repaired in tissues of rats receiving high lethal doses. Results suggest that the unhooking of ICL, which we followed with the comet assay, may lead to the formation of another toxic DNA lesion during the repair process., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim: The purpose of this study was to investigate the Prostate Health Index as a marker for tumor aggressiveness in prostate biopsy and the optimization of indication for treatment options., Methods: Our cohort consisted of 320 patients indicated for radical prostatectomy with preoperative measurements of total prostate-specific antigen, free prostate-specific antigen, [-2]proPSA, calculated %freePSA, and Prostate Health Index. The Gleason score was determined during biopsy and after radical prostatectomy. Using the Gleason score, we divided the group of patients into the 2 subgroups: Gleason score ≤6 and Gleason score >6. This division was performed according to the biopsy Gleason score and according to the postoperative Gleason score. We compared total prostate-specific antigen, [-2]proPSA, %freePSA, and Prostate Health Index in the subgroups Gleason score ≤6 and Gleason score >6 after biopsy and the definitive score., Results: On evaluation of the subgroups created by Gleason score ≤6 and Gleason score >6, we observed agreement between biopsy Gleason score and definitive Gleason score in only 45.3% of cases. Of the calculated biopsy, Gleason score ≤6 and Gleason score >6 subgroups, [-2]proPSA, and Prostate Health Index ( P = .0003 and P = .0005) were statistically significant. Of the definitive Gleason score ≤6 and Gleason score >6 subgroups, Prostate Health Index, [-2]proPSA, %freePSA, and PSA ( P < .0001, P < .0001, P = .0003, and P = .0043) were statistically significant. The best area under the curve value (0.7496) was achieved by Prostate Health Index when the subgroups were established according to the postoperative Gleason score., Conclusion: Prostate Health Index is the best of the tested markers for the categorization of Gleason score 6 tumors and for facilitating the management of patients with prostate cancer. Prostate Health Index can be a helpful marker for indication of active surveillance or radical prostatectomy. Prostate health index can also simplify the decision of whether to perform nerve-sparing radical prostatectomy.

The purpose of this study was to evaluate the efficacy of potential candidate molecules or their combinations against strong alkylation agent sulfur mustard (SM) on the human lung alveolar epithelial cell line A-549. Candidate molecules were chosen on the basis of their previously observed protective effects in vitro. The tested compounds, including antioxidants, sulfhydryl or other sulfur-containing molecules, nitrogen-containing molecules, PARP inhibitors and a NO synthase inhibitor, were applicated 30min before SM treatment. The efficiency of candidate molecules to protect cells against DNA damage and cell death induced by SM was determined using single-cell gel electrophoresis (comet assay) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction by viable cells. The damage of DNA was assessed 1 and 24h after dose 50μM SM. Cell survival was assessed 24 and 72h after the exposure. To achieve maximal cytoprotection, combinations of selected compounds with sodium 2-mercaptoethane sulphonate (MESNA) were tested. We found significant protective effects by several drugs used individually and also in combination with MESNA. High protection was achieved by sodium thiosulphate, which was further potentiated when combined with MESNA. Most of the selected compounds or mixture provided only moderate genoptotection without having any effect towards cell viability., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Sulfur mustard is a highly toxic chemical warfare agent with devastating impact on intoxicated tissues. DNA cross-links are probably the most toxic DNA lesions induced in the cell by sulfur mustard. The comet assay is a very sensitive method for measuring DNA damage. In the present study using the A-549 lung cell line, the comet assay protocol was optimized for indirect detection of DNA cross-links induced by sulfur mustard. The method is based on the additional treatment of the assayed cells containing cross-links with the chemical mutagen, styrene oxide. Alkali-labile adducts of styrene oxide cause DNA breaks leading to the formation of comets. A significant dose-dependent reduction of DNA migration of the comet's tail was found after exposing cells to sulfur mustard, indicative of the amount of sulfur mustard induced cross-links. The remarkable decrease of % tail DNA could be observed as early as 5min following exposure to sulfur mustard and the maximal effect was found after 30min, when DNA migration was reduced to the minimum. Sulfur mustard preincubated in culture medium without cells lost its ability to induce cross-links and had a half-life of about 15min. Pre-incubation longer than 30min does not lead to a significant increase in cross-links when applied to cells. However, the amount of cross-links is decreased during further incubation due to repair. The current modification of the comet assay provides a useful tool for detecting DNA cross-links induced by sulfur mustard and could be used for detection of other DNA cross-linking agents such as chemotherapeutic drugs., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Sulfur mustard (SM) is a blister agent with cytotoxic mechanism of action. There is no suitable treatment based on administration of an antidote. In this study, Wistar rats were exposed to SM in doses of 0-40 mg/kg body weight and treated with the compound HI-6. The treatment provided no significant effect on ferric reducing antioxidant power of blood and plasma. However, HI-6 caused an increase in the level of thiobarbituric acid reactive substances. This stressogenic response was presumably the cause of the significant elevation of the blood level of both glutathione reductase and reduced glutathione. HI-6 appears to be suitable for enhancing prophylactically oxidative stress protection from small oxidative insult.

Sulfur mustard (SM) is a chemical warfare agent with cytotoxic effect and a tight link to oxidative stress (OS). Depletion of antioxidants is considered as a cause of detrimental consequence and belongs to the important steps leading to cell death. The oxidative injury appearing after SM exposure is not well understood. Nevertheless, identification of the pathological processes would be a good opportunity to establish an efficient therapy. Here, we focused our effort on an estimation of reactive oxygen species homeostasis and apoptotic processes in Wistar rats exposed to 0-160 mg/kg of SM. We assayed antioxidant activity, thiobarbituric acid reactive substances, reduced glutathione/oxidized glutathione, metallothionein, glutathione reductase, glutathione peroxidase, glutathione S-transferase, caspase 3, and glucose in the livers, kidneys, and muscles of the animals. Significant OS, depletion of low-molecular-mass antioxidants, increase in caspase activity, and some other processes related to SM action were determined. Moreover, we infer a principal role of OS in the tested organs.