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This article introduces a bio-psycho-socio-spiritual model of the Holocaust impact on health. On the empirical level, the way to achieving the set goals leads through qualitative field research using the Interpretative Phenomenological Analysis approach. Three groups of respondents (Holocaust survivors, 2^nd generation of survivors and experts from helping professions who have experience with survivors care) were linked to ensure the validity of the stated conclusions. The main technique for data collection was a semi-structured interview. The data were analyzed using Atlas.ti software, following the IPA recommendations.The results refer to a wide range of physical impacts (e.g. osteoporosis, flat-foot, degenerative spine diseases, chronic pain, stomach and duodenal ulcer, chronic skin defects), mental impacts (e.g. PTSD, distrust, suspicion, vigilance, inferiority complex, annoyance in connection with the German language, specific attitude to food), social impacts (loss of property, marriages of convenience, need for education, inclination to care about weaker persons) and spiritual health impact (guilt, loss of faith in God, strengthening of Jewish identity, need to pass experience). Holocaust survivors are characterized by being interested in their health. Since the time of internment they have had their daily healing rituals, such as morning stretching exercises, yoga, cold baths, airing. Cleanliness of the body (especially the hands) and the environment are very important for all survivors. For most of them it is important to keep their mental health in good condition. That is the reason why they often attend various educational activities and if they are able to travel they do that. Research on the Holocaust Survivor Group represents the integration of resilience and vulnerability, desire for life, and the ability of a person to survive and live in extreme conditions. Using the example of this study examining the impact of trauma on health in all of its dimensions, it is possible to predict the future health problems of specific groups of migrants in connection with war conflicts and other life-threatening situations.

Background: Several alternative prevention strategies are being employed in various clinical settings to reduce Contrast-induced nephropathy (CIN). Despite the proposed theoretical advantage of these strategies, there is no agreement on their relative effectiveness in real practice. This study aimed to estimate the incidence of CIN and to report on the real effectiveness of sodium bicarbonate to protect the kidney from CIN in various cardiac patients undergoing cardiac catheterization.Methods: This is a retrospective, single-center, cohort study. A total of 60 patients admitted between January 2016 and November 2021 who were undergoing coronary angiography at a single Saudi center were included.  All patients received either intravenous sodium bicarbonate or normal saline hydration prior to, during, and after the implementation of CM.  CIN was defined as serum creatinine (SCr) ≥ 25% or ≥ 0.5 mg/dL compared to the baseline value within 48 h after CM exposure.Results: Among all patients, the incidence of CIN at 24 and 48 h was 16.7% and 15%, respectively. Strikingly, the incidence of CIN at both time points was significantly higher among patients who received sodium bicarbonate than among those who received normal saline hydration only [30% vs. 3.6% (P=0.012) and 38% vs. 3.3% (P=0.002), respectively].  Dyslipidemia status was the most positive predictor of CIN incidence at both time points.Conclusions: The 16.7% incidence of CIN in this sample is considered very high compared to the rates in previous national and international studies.  This finding indicated that further preventive measures should be urgently initiated with strict protocols for the implementation of CM according to updated guidelines.

Recently, a significant improvement in treatment outcomes throughout hematologic malignancies has been achieved. Innovative treatment approaches require new modalities of supportive care. In this article, we review common requirements on supportive care in oncology and hematopoietic cell transplantation and elucidate the reasoning of this treatment. Due to similar organ affection as in patients after high-dose chemotherapy, we also find possibilities of applying these procedures in patients after high-dose external irradiation. Further, we describe new requirements on supportive care in hematology. Our aim is to increase the general knowledge about severe immune suppression and specific complications in these patients, which can be useful throughout internal medicine and surgery disciplines.

Vitamin D inadequacy is widespread in females with polycystic ovarian syndrome (PCOS), with blood values of 25-hydroxy vitamin D (25OHD) down to or less than 20 ng/ml in two-third of PCOS patients. Decreased 25OHD concentrations have been linked to insulin resistance, ovulatory and period abnormalities, lower pregnancy outcomes, and other indications of PCOS, according to epidemiological studies. There might be some, but inadequate, research that vitamin D supplements can help women with PCOS with menstruation disruption and insulin sensitivity. Vitamin D inadequacy may bestow to the exacerbation of PCOS, and vitamin D intake may be helpful in the treatment of this condition. However, the present evidence is insufficient, and further experimental investigations are in need to establish vitamin D supplementation's potential advantages in this population. Many investigators claimed a pertinency between vitamin D concentrations and PCOS, nevertheless, these researches bear rattle factors of conjoined with other disorders or ailments, such as obesity, diabetes, and hirsutism. In the view of this, the present review detailed the role of vitamin D inadequacy and related biomolecule abnormalities, including sex hormones, and insulin and we listed their psychological and cardiovascular encounter. We concluded that the correlation between vitamin D intake and mended PCOS prominence is dubious and no definite findings attained by studies conducted across multicentral laboratories.

Society, as much as an individual, has a certain capacity to cope with issues. The preparedness of the society for the issue significantly enhances the ability to overcome the issue with minimum possible harm. This article considers psychological consequences of climate change, the major challenge for society, from the perspective of European security. It proposes an increasement of aggressive behavior and intergroup hostility as a direct and indirect psychological consequence of climate change. In the final section, crisis intervention and de-securitization of climate change debate are considered to serve as mitigating factors for future development.

Usutu virus (USUV) is an emerging mosquito-borne pathogen belonging to the genus Flavivirus and family Flaviviridae. This African arbovirus caused a large bird die-off near Vienna in 2001. Since then the virus spread in Central, Southern and Western Europe. USUV is a primarily pathogen of birds, highly pathogenic especially for blackbirds (Turdus merula), but with proven pathogenicity for other bird species, mainly from orders Accipitriformes and Strigiformes. However, the number of human cases of USUV infection has increased recently. In this review, we summarize the current knowledge on USUV taxonomy, its genome, transmission cycle involving mosquitoes as vectors and vertebrate hosts, endemic occurrence in Africa and expansive spread in Europe, surveillance in individual European countries, pathology and clinical manifestations in vertebrates, laboratory diagnosis of infection and available treatment.

Emerging, as well as existing and known infectious threats represent a constant challenge in ensuring blood safety and blood transfusions. In addition to non-contributory donations and careful selection of blood donors and its components, robust laboratory screening procedures represent a significant complementary alternative in increasing the safety of transfusion products, the so-called pathogen reduction. This brief review article summarizes information on the principle and application of pathogen reduction technologies in transfusion medicine, as well as the latest research on their possible future application.

Faculty of Military Health Sciences, University of Defence, Hradec Králové, Czech Republic (FMHS), collaborate with Colleagues and Centres of National University of Ireland, Galway (NUIG) on the security research and development of new types of countermeasures against the biological agents for several years. Based on the numerous discussions with the Prof. Lokesh Joshi (NUIG), a longer-term cooperation between these two institutions was established. ...

At the beginning of January this year, we celebrated a significant milestone in the life of Major General (ret.) Roger Van Hoof, MD, a distinguished personality and international authority on military medicine. He is a former Surgeon General of the Belgian Army, long-time Secretary-General and current Honorary Secretary-General of the International Committee of Military Medicine (ICMM). On this occasion, we would like to recall at least some of his life and career highlights. ...

The autor describes the new combat food rations in the Army of the Czech Republic. He informs about the food rations, combat rations, energy value, nutrients in the combat food rations. Benefits of newly proposed food benefits and possible trends for further development in catering security of the Army of the Czech Republic in field conditions are contained in the thesis.

The ventricular septal defect (VSD) is a congenital lesion characterized by the presence of an opening between cardiac chambers. The treatment might involve medical therapy to control symptoms or in certain cases, surgical resuscitation might be required.Objectives: The study was conducted to establish a database about the prevalence and pattern of VSD and their prognosis in children referred to by echocardiography in Ibn-Sena Teaching Hospital over the period of March 2019 to January 2020. Method: The present study is a prospective descriptive study conducted on all patients diagnosed with cardiac lesions revealed by echocardiography. The sample included in the study involves newborns (day 1) to 14-years-old children.Result: Out of 500 children included in the study; most of these cases were cyanotic congenital heart lesions and out of which two-third were perimembranous defects.Conclusion: The study concluded a higher prevalence of non-cyanotic lesions and peri-membranous type is the commonest VSD lesion.

Background: There are scarce data on disease characteristics and severity of coronavirus 2019(COVID - 19) among Iraqi patients with rheumatic diseases (RDs). In this study, we aimed to report the disease characteristics and variables associated with COVID-19 outcome among patients with RDs.Methods: Between October 2020 and April 2021, rheumatic diseases (RDs) patients with COVID-19 were registered from different centres in Iraq. The patient's demographics, rheumatological history, COVID-19 symptoms, severity, and management, if any, their disease progress and outcome have been assessed. Binary logistic regression analysis was performed to determine predictors of disease severity.Results: 253 patients were included in the study, and most were females. The commonest rheumatic disease was rheumatoid arthritis (RA), followed by systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS) (95, 52 and 20 patients respectively). It has been found that 50.6% of patients had mild COVID-19, and 49.4% had moderate disease; 18% of patients required oxygen support, no patient was treated in hospital, and there was no reported death. Patients with moderate COVID-19 had significantly higher age than mild type (p= 0.022); with more BMI (p=0.03), more in the number of comorbidities (p<0.001), more steroids users (p=0.012), higher steroid dose (P=0.034), had longer steroid duration,   longer duration of conventional disease-modifying antirheumatic drugs (cDMARDs) (p=0.018), and biologic Disease-modifying Antirheumatic Drug (bDMARDs) in months (p=0.025). Increasing body mass index (BMI), duration of biological DMARDs use, and an increasing number of comorbidities were significant independent factors that increase the risk of having more severe COVID-19, (p<0.05).Conclusion: COVID-19 infection rheumatic patients tend to have mild-moderate disease course; BMI, duration of biological DMARDs use, and many comorbidities were significant independent factors that increase the risk of having more severe COVID-19.

Introduction: The novel corona virus (SARS-CoV-19) is mainly accountable for the disease outbreak infection, which began in Wuhan, China, in 2019. Numerous modest research has been carried so far to ascertain the risks of smoking on the magnitude, consequence, and morbidity of patients with COVID-19, but the findings have been incomplete.Aims: This study assesses the effects of current smokers on the magnitude and consequence in patients with COVID-19 infectious disease in Mosul, Iraq.Materials and Methods: A total of 160 patients (80 active smokers and 80 non-smokers) who were confirmed with COVID-19 infection using polymerase chain reaction (PCR) test were enrolled in this study. A detailed history was obtained from of the subjects, as well as a thorough clinical evaluation and laboratory tests. The intensity of illness, biomarkers, D-dimer, liver enzymes (LFT), oxygen consumption, hospitalization, and outcome were all documented and analyzed between a two groups.Results and conclusion: The symptoms of COVID-19, measured laboratory markers were significantly higher in the sample of smokers compared to non-smokers. There has been no significant difference in the use of oxygen, hospitalization, ICU admission, death, or post-recovery problems. Serious clinical COVID-19 infection was much more prevalent in current smokers, and inflammatory markers such as D-dimer and LFT appeared greater in non - smokers than in smokers. There was no statistically significant difference in O2 usage, hospitalization, ICU admittance, death, or persistent morbidity.

Smart hydrogels are special type of hydrogels that undergo solution-gelation transition in response to alterations in the environment. Solution-gel transformation is brought about through either physical or chemical cross-linking that occur between the hydrogel chains. Various stimulating factors have been identified to be responsible for the change in the physical state of the intelligent hydrogel. The most important triggering factors are the temperature, pH, ions, electrical signalling, magnetic field, glucose, light and others. Each of these stimulating factors can trigger the swelling of the hydrogel through unique mechanism. Many of these triggering factors are characteristics of the biological systems which make the smart polymers quite beneficial for different biomedical applications. Numerous natural and synthetic polymers have been distinguished to act as smart materials. These polymers impressed the scientists to use them in many biomedical and industrial applications such as drug delivery systems, gene therapy applications, tissue engineering and many other applications.

Microbial enzymes are used in a wide range of industrial production, in pharmacy, medicine or as part of detection methods or biosensors, due to low-cost production in short time. Immobilization of enzymes on solid surfaces has been shown to improve essential requirements, such as higher efficiency of the enzymatic reaction per unit time, better pH and thermo stability, repeated use, easy separation of enzyme and long-term stability. In industry, immobilization is used in food production processes, in detergents and their preparation, in the textile industry or in the production of biofuels. In pharmacy, immobilized enzymes are a part of the production of drugs, or as a part of drugs themselves, in medicine, immobilized enzymes are used to treat or diagnosis of diseases. Immobilized enzymes are a suitable part of detection methods, segment of biosensors for the determination of specific markers of poisoning and diseases, also are used for the determination of water and soil pollution or as an ecological variant replacing toxic chemicals. Immobilization of enzymes on solid surfaces is used in many areas and offers great potential for the future.

Every year many drug molecules discovered to be effective in treatment of many diseases, however not all of these drugs succeed in reaching the market. One of the main reasons for such failure is the lipophilicity or low water solubility of these chemicals which results in poor bioavailability. Nanoemulsion has the ability to deliver these drugs in an efficient way. Nanoemulsion, which is usually o/w emulsion can incorporate this lipophilic drug into nanolipoidal droplets. However, the difficulty in applying liquid dosage form can be overcome by using nanoemulgel system. Nanoemulgel considered as a suitable way to deliver lipophilic drugs through topical route. This review tries to highlight the importance of nanoemulgel as a drug delivery system. The components of the systems have been explored and the methods of preparations including high energy methods and low energy methods have been discussed. Different methods were used in characterization of such delivery system; all of these methods and techniques were reviewed briefly. Finally, the recent researches about different applications of emulgel in local delivery or systemic delivery has been discussed. To conclude, the nanoemulgel applications in drug delivery is very promising and many products will find their way to the markets soon.

Based on many reports, an unmistakable link probably exists between diabetes mellitus and COVID-19. A major predisposing factor determining severity and mortality of COVID-19 is diabetes mellitus, diabetic patients were shown to be at higher risk for developing severe COVID-19 disease than non-diabetics; many recent studies reported a striking prevalence of DM in those diagnosed with COVID-19. Accordingly, antidiabetic drugs can possibly impact the clinical course and / or the outcome of this infection, either by alleviating diabetes-associated symptoms, minimizing its complications, or by mitigating or aggravating COVID-19 disease by effects independent from their direct antidiabetic effects. Several antidiabetic drug classes were shown to have varying effects, like blocking viral entry to cells, as well as having immunomodulatory, anti-inflammatory, antifibrotic, or cardioprotective effects; such effects could prove beneficial for COVID-19 patients. On the other hand, some antidiabetic agents may have adverse effects that aggravate patients’ condition like hypoglycemia, fluid retention, increased weight or lactic acidosis, which require special consideration in patient management. Some of the drugs were found in observational studies to either reduce mortality from COVID-19 or pose no harm, but more solid evidence from clinical trials is still lacking.

Prof. Jaroslav Kačerovský, MD PhD was born on March 29, 1934 in Vlastějovice in the Kutná Hora region. His compulsory school attendance was affected with the war years, his secondary school studies are then connected with memories of the town of Ledeč nad Sázavou. In 1953, he passed the school-leaving examination at the local grammar school. ...

During the last weekend of February, from Friday 25 February to Saturday 26 February 2022, a workshop was held at the Rajská zahrada hotel in Nové Město nad Metují, marked by lectures and discussions on the application of modulators of biological reactions.

Brigadier General (ret.) Associate Professor Leo Klein, MD, CSc., a distinguished personality of the Czech military medical service and international authority on military medicine, will celebrate a significant jubilee on April 18^th, 2022. He will celebrate his seventieth birthday in the full vigour of life and work. Seventy years of a fulfilling and creative life, significant and ordinary moments, just the way life should be.

Many natural (poly)phenolic compounds including flavonoids are able to chelate biological trace metals such as iron, copper and cobalt. On the other hand, they are also frequently reducing these metals to lower oxidation states. Although this later reduction process is commonly understood as an antioxidant effect, it might be also associated with recovery of the catalyst in the known metal-catalyzed Fenton chemistry and can hence paradoxically lead to a tissue damage (pro-oxidation). For this reason, the final biological outcome ensuing from (poly)phenol-metal interaction varies from compound to compound depending on the individual differences in chelation and reduction toward the selected metal, and abilities to directly scavenge reactive oxygen species such as hydroxyl radical. Firstly, chelation properties of a row of flavonoids toward iron, copper and cobalt will be discussed. This will be followed by comparison of their ferric and cupric reducing capacity, ability to inhibit or potentiate iron, copper and cobalt triggered Fenton reaction and to block or stimulate metal-based red blood cell lysis. Also limited in vivo pro-oxidation data from rats will be mentioned.

Organophosphorus compounds (e.g. nerve agents - sarin, VX or tabun) cause deleterious intoxications via inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) leading to cholinergic crisis or even death of intoxicated person. Their causal treatment is managed by oxime reactivators (e.g. pralidoxime, obidoxime, asoxime), which are primarily restoring function of AChE via nucleophilic oximates and thus safe a life.
Recently, we have proved that nucleophilicity of oxime reactivators may be improved by using other substituents attached to the close proximity of the oxime moiety. Such modifications are leading to the increased formation of oximate nucleophile and thus to the increased reactivation of phosphylated cholinesterases. In particular, the substitution by chlorine atoms led to the powerful and rapid reactivation of sarin, cyclosarin or VX-inhibited AChE in vitro (1) or in vivo (2). On the other hand, the substitution by fluorine atoms led to even higher nucleophilicity, but also rapid depletion of oximes into isoxazole degradation products (2-3). Interestingly, some further modified reactivators were proved to be effective in vitro to simultaneously restore function of AChE and BChE.

The mercury is a persistent and whidespread heavy metal with neurotic effects in wildlife. To determine the overall mercury exposure in the locality Zastávka u Brna (Czech Republic), total of 71 great mouse-eared bats (Myotis myotis) building demolition casualties (23 male and 48 female) were examined. Bats were classified as juvenile or adult. The 71 samples of fur, muscle and wing membrane were collected for analysis to determine total mercury concentrations (THg). The THg was determined by cold vapour atomic absorption spectrometry using AMA 254 analyzer (Altec Ltd., Dvur Kralove nad Labem, Czech Republic) in the fresh weight. The THg measured values ranged from 1.7 to 20.0 mg.kg-1, from 0.05 to 0.25 mg.kg^-1 and from 0.03 to 0.19 mg.kg^-1 in the fur, muscle and wing membrane, respectively. The mean THg content in the fur, muscle and wing membrane was 6.2±4,03 mg.kg^-1, 0.1±0.041mg.kg^-1 and 0.084±0.03 mg.kg^-1, respectively. There was no difference between THg values in males and females as well as in the study by Åkerblom et al. (2017). The positive correlation between THg content in analyzed tissues were found (fur and muscle p=0,000; r_s= 0.5501; muscle and wing membrane p=0.000, r_s=0.5567; wing membrane and fur p=0.000 r_s=0.9997). According to Zukal et al. (2015) the bats are suitable trophic guild as an indicator of general environment condition.

Non-alcoholic fatty liver disease (NAFLD) is a pathological state characterized by the excessive accumulation of triglycerides in hepatocytes without alcohol consumption. NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), which can further progress to cirrhosis and hepatocellular carcinoma (1). Xanthohumol (XN), a hop-derived prenylflavonoid, has been reported to ameliorate steatosis, inflammation, and fibrosis in murine NAFLD models (2). This study aimed to investigate the effect of XN on the expression of antioxidant enzymes in an in vitro model of NAFLD. For this purpose, fat accumulation was induced in murine precision-cut liver slices (PCLS) with a medium containing fatty acids (mixture of oleic and palmitic acid), fructose, and citrate. PCLS were treated with 10 µM XN in the presence or absence of 1 µM insulin for 24 and 36 h. The mRNA expression, specific activity of the main antioxidant enzymes, and triglyceride content were determined. Specific activities of glutathione peroxidase and glutathione S-transferase (GST) were decreased after 24 and 36 h in PCLS treated with the steatotic medium and only a slight increase in response upon XN treatment was observed. In steatotic PCLS, XN caused significant increase in the mRNA expression of NAD(P)H: quinone oxidoreductase 1, GSTA1/2, and GSTM3 after 36 h. The influence of XN on the protein expression of these enzymes will be further studied.

Polyaromatic hydrocarbons (PAHs) are a diverse group of environmental and dietary contaminants. PAHs are primarily metabolized through the aryl hydrocarbon receptor (AhR)-regulated enzymatic pathway. Both parent PAHs and their metabolites may exert various types of toxicity in target cells and tissues. In addition to their well-known genotoxic (and carcinogenic) effects, PAHs may alter numerous additional cellular events, including cell metabolism. In this project, we study whether strong AhR ligand benzo[k]fluoranthene (BkF) can modulate genes associated with glucose and lipid metabolism, as well as proteosynthesis, which is essential metabolic process performed at high energetic cost. We used an in vitro model of immortalized human hepatocytes, MIHA cell line. We observed a significant suppression of proteosynthesis induced by BkF in MIHA cells, as determined by the SUnSET method. We also observed a moderate deregulation of several genes associated with further evaluated metabolic processes. Based on this, we continue to evaluate possible impact of strong AhR ligands, such as BkF, on cellular metabolism, as well as functional role of this transcription factor in the complex effects of PAHs on cellular metabolism.

The ISO standard 10993 for medical device testing was accepted over three decades ago. During that period, ISO standard was changing and adapted based on the growing knowledge on adverse effects and regulatory needs. The term, medical devices, includes various products that are used in medicine, but their terapeutic effect is not acchieved by pharmacological, immunological or metabolic means. These products have different mechanical, physical and chemical properties. The procedures described in the ISO 10993 cover testing of raw materials as well as final products. However, composition of  medical devices can be quite complex, and it may sometimes be challenging to follow procedures laid down by the ISO 10993. The ISO 10993-12, reviewed in 2021, describes in detail the essentials of the sample preparation undergoing the in vivo or in vitro testing (i.e. extraction into polar and non-polar solvents). Unfortunately, there is only a little guidance for materials absorbing the extraction solvents  (ISO, 2018; ISO, 2021a; ISO, 2021b).
In our study, we tested medical devices used in dental/oral care. Among these products are adhesive pasted for dentures and cream for ulcer treatment. These formulations have shown to be highly solvent absorbing. We have performed several procedures for extracting such materials, using different ratios of the material/extractant and including/excluding the orbital shaking of the sample. The achieved extracts were subsequently tested in line with the ISO 10993-5 using 3T3 NRU assay and ISO 10993-23 using 3D reconstructed human tissue model of epidermis and another, non-keratinised epithelia, used to mimic the soft tissues in the oral cavity.
The results show that the exctract preparation procedure considerably influenced the results of the experiments. In the static conditions, the preparations showed significantly lower cytotoxic proppetries compared to the mixed extracts. Non-keratinised 3D epithelial tissue model was more sensitive to the preparations than 3D skin tissue, as expected. The testing battery helped us to predict possible side effects of the selected MD materials used in the oral cavity.

Oxime reactivators are causal antidotes commonly used against organophosphate (OP) poisoning. Although OPs are utilized in agriculture as pesticides, they can be misused by terroristic groups as nerve agents (NA). These compounds are fast acting inhibitors of human acetylcholinesterase (AChE) causing cholinergic crisis ultimately leading to death by respiratory failure. Treatment of OP intoxication consists of immediate administration of symptomatic drugs, namely, atropine and diazepam and antidotes in form of oxime reactivators of AChE. Undoubtedly commercially used reactivators are the best countermeasure for OP intoxications so far, however they have several downsides. First of all, there is no broad-spectrum reactivator effective against all NAs, secondly they cannot reactivate “aged” form of AChE and lastly they poorly cross the blood-brain barrier (BBB) due to low lipophilicity (1). For instance, widely used reactivator 2-PAM crosses the BBB approximately from only 10% (2). However, most of the techniques used for measuring the concentration of reactivator crossing BBB are relying on HPLC combined with MS or UV detector. BODIPY probe could be great alternative as it is a strongly fluorescing probe standardly used for imaging techniques in vitro (3). The aim of this work is in vitro evaluation and analysis of physicochemical properties of BODIPY labeled oxime reactivators of AChE.

Signal transducer and activator of transcription-3 (STAT3) is the most studied member from seven latent cytoplasmatic transcription factors (STATs 1-4, 5a, 5b and 6) that are closely associated with the occurrence of many types of cancer (breast, leukemia, lung, lymphoma, ovarian and prostate). STAT3 contains four functional domains, from which the Src homology 2 domain (SH2 domain) is the major target for inhibition of these proteins. Inhibition results in STAT3 tyrosine 705 (Y705) phosphorylation, dimerization, nuclear transport, DNA binding and transcription induction. The benzo[b]thiophene 1,1-dioxide (BTP) as a pharmacophore is part of many STAT3 inhibitors, such as Stattic, HJC0123, HJC0149 and HJC0416 (1,2,3). Stattic (6-nitro derivate of BTP) is a small molecule which selectively inhibited STAT3 SH2 domain function in vitro (3). HJC0123, HJC0149 and HJC0416 are carboxamides made from 6-amino derivate of BTP and substituted aromatic carboxylic acids (1,2). In this study we have in silico designed, synthesized and purificated 8 new Stattic-carboxamides. Their physical chemical properties were predicted in silico and then experimentally evaluated. Their biological activity was tested on murine and human cancer cell lines. Results were evaluated and compared to Stattic as a reference compound.

Neurotoxicity is commonly associated not only with neurodegenerative damage but also with organophosphate intoxication. Neuronal death may be associated with acute and life-threatening symptoms and subsequent long-term secondary disorders. This study focuses on the development and validation of a cellular model of mature human neurons. A model was obtained by differentiating the neuroblastoma cell line SH-SY5Y. In vitro cell model is suitable for studying neurotoxicity and its potential countermeasures. The protocol involved stimulation of the cell line with retinoic acid and brain-derived neurotrophic factor for 9-12 days. Observation of morphological signs of neurons (characteristic synaptic connections), using lighting microscopy and a detection of specific neuronal markers (tau protein, microtubulle-associated protein (MAP), synaptophysin (SYN), post-synaptic density protein (PSD-95)) using fluorescence microscopy was used for validating this model. Another experiment was focused on the quantification of acetylcholinesterase in differentiated and undifferentiated cells. As a result, it has been shown that the level of enzyme in the differentiated cells is significantly higher than in the original undifferentiated cells. Another planned use of the model is in vitro testing of the neurotoxic effects of organophosphates and screening of potential prophylactics or drugs for the treatment of neurodegenerative injuries.

Nowadays, pyrethroids (e.g., flumethrin and tau-fluvalinate) are commonly used in apiculture as an active ingredient of several authorised veterinary medicinal products (acaricides) licensed worldwide. The beekeepers who regularly use synthetic acaricides throughout the year may potentially put the bee colonies at risk. Pyrethroids are frequently related to long half-life inside the hive matrices, which may adversely affect the health of bee colony. In this project we assessed potential harmful lethal and sublethal effects of synthetic acaricide tau-fluvalinate (tech.) on winter adult honeybees according to OECD 245 (2017). In vitro reared winter honeybees showed no dose-dependent mortality after the oral 10-days exposure to sucrose solution (50% w/w) spiked with a maximum concentration of 750 μg a.i./kg diet and its 1/10 value. The No Observed Effect Concentration (NOEC) appears to be higher than or equal 750 μg a.i./kg diet. The results of tau-fluvalinate testing for the potential sublethal genotoxic effects showed that that pyrethroid tau-fluvalinate at tested concentrations induced significant levels of DNA damage in bees, which may result in a potential genotoxic effect.