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Taking into account the events of recent years, a risk of exposure to high toxic substances including chemical weapons is not negligible. Therefore the Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defence introduced analytical and biological samples (plasma, urine) preparation methods for determination of biomarkers of exposure to nerve agent (sarin, cyclosarin, soman, tabun, VX and VR agent) and sulphur mustard. Evidence of chemical weapon use is based on detection of their metabolites (Alkyl methylphosphonic acids as metabolites of the organophosphorus nerve agents, thiodiglycol as a metabolite of sulphur mustard) and products of their reactions with biomolecules (tyrosine adducts of organophosphorus nerve agents, sulphur mustard-albumin adducts). Gas chromatography tandem mass spectrometry and liquid chromatography tandem mass spectrometry are used for determination of biomarkers. Functionality of described methods is validated and discussed participating in Biomedical proficiency test, which is organized by The Organisation for the Prohibition of Chemical Weapons every year.

As of 14^th July 2020, 12,964,809 confirmed cases of coronavirus (COVID-19) and 570,288 deaths had been reported globally. In Kuwait, the numbers stood at 55,508 confirmed cases and 393 deaths. The disease seems to be hitting hard on the country despite the measures that have been put in place. The current study sought to examine healthcare workers HCWs awareness and perceptions of coronavirus disease in Kuwait hospitals. A prospective study design was used to examine the development of the disease among 28 HCWs between mid-May and the start of June 2020. The primary findings were as follows; most of the study participants had attended lectures/ discussions on COVID-19, only few HCWs could identify the incubation period of the novel coronavirus. However, the majority could identify the most common symptoms of the disease as fever, cough, headache, sore throat, runny nose, and skin rashes. Most of the HCWs were aware that the virus transmitted through contact. A good number of the study participants also identified pneumonia, respiratory failure and death as complications associated with coronavirus disease. The study recommends running health education programs in Kuwait to promote knowledge on the coronavirus and help the HCWs develop positive attitudes and uphold important practices.

Early changes after radiation exposure may serve as predictors as well as targets for alleviation of radiation-induced injury in the lung. The aim of our study was to examine alterations on the cell and tissue levels in the lung and blood changes of immunological and cytokines profiles induced by ionizing radiation (IR) during the first month after irradiation in the mice experimental model. Female C57BL/6 mice were total body irradiated (TBI) by 8 Gy. Lung tissue samples and blood and were collected 4, 8 and 24 h, 7, 21 and 30 d after TBI. We measured absolute cell counts, cell populations and cytokines profile in the blood and evaluated histopathological analysis in the lung, immunophenotypization of the main lung cell populations and cytokine profiles. In blood, the acute radiation syndrome developed with recovery being observed at 21 – 30 d, observed by hematological markers. In the lung tissue, a biphasic response occurred. At first, a significant decreased of lymphocytes, resident tissues macrophages and air/tissue ratio associated with increased neutrophils was observed at 8 – 24 h. Subsequently, increase in infiltrating CD4+ T-lymphocytes, neutrophils and resident tissues macrophages and decreased airiness were measured 21 and 30 d after TBI. In summary, our study describes the mechanisms that lung tissue enables to cope with non-lethal injury.

Pharmacists are responsible for dispensing drugs and protecting the patient by making sure that they use drugs appropriately. They play an important role not only in the overall cost implications of healthcare but also in the concerns about patient safety when using medication. The scope of this paper was to evaluate the practice of navigation of medical resources among pharmacy students through a simulated event of acute kidney injury using a prospective research methodology. A sample of 65 students was used, among which 2 failed to identify the error in dosing (3.1%) while 56 (86.2%) responded with the presence of error in renal dosing and recommended correctly. Only 7 (10.8%) of the study population had an incomplete recommendation. Even though a greater percentage of the student populations were able to identify dosing errors, there were a few that were unable to identify the errors. Even though this percentage is small, it is much significant when placed in various healthcare institutions and is likely to have a significant impact on patient safety.

Lead (Pb), which is widely used in industry, is a common element found in low concentrations in the Earth's crust. Lead has been used since prehistoric times. As a highly toxic heavy metal, the pollution and exposure risks of lead are of widespread concern for human health. This environmental contaminant causing irreversible health effects mainly in children. Especially children under the age of six are most at risk for lead poisoning. Lead toxicity causes hematological, gastrointestinal, and neurological dysfunction. Symptoms are usually noted with blood lead greater than 2 μmol/litre. Severe or prolonged exposure may also cause chronic nephropathy, hypertension, and reproductive impairment. Lead inhibits some enzymes, alters cellular calcium metabolism, stimulates synthesis of binding proteins in kidney, brain, and bone, and slows down nerve conduction. The emission sources and pathological effects of lead are discussed.

The evolution of varicella zoster virus lasts more than 400 million years. While primates were the original reservoirs of the virus, subsequently VZV started to circulate in human population and humans have been the exclusive hosts for VZV for more than 45 000 years. VZV is a highly contagious and neurotropic herpetic virus a member of the herpesviridae family.Its primary infection results in typical signs of varicella (chickenpox). After that, the virus establishes lifelong latency in trigeminal and dorsal root ganglia. Endogenous viral reactivation, thought to be associated with waning VZV specific T cell mediated imunity, leads to herpes zoster (shingles), especially in older adults and immunocompromised persons (VZV is the only human herpetic virus exhibiting entirely different clinical picture).

New and modern techniques of drug design are extensively used in parallel or instead of the classic ones. Applicability of virtual screening (VS) is growing with the computational performance. This article includes list and short description of most frequent used methods in VS. These methods are divided into two groups - ligand-based VS and structure-based VS. Ligand based methods include chemical similarity, pharmacophore and quantitative structure-activity relationship. Molecular docking and scoring are methods of the structure-based VS.

Hops are a well-known source of resins, essential oils and polyphenolic substances, such as proanthocyanidins or prenylflavonoids with significant representatives of xanthohumol, isoxanthohumol, and 8-prenylnaringenine, and represent an essential ingredient in beer production. Recently, however, many additional bioactive effects of hop compounds have been investigated.A systematic review of the structure-function relationship between the individual hop-derived compounds and their bio-activity has been lacking. In this review we summarize some recent findings in this area from reports from our as well as other studies. It shows multiple bio-medical effects of the individual hop derived compounds, which can act individually, or in a synergistic manner.The hops can serve as a source of bio-active compounds in phyto-medicine and as such, more attention and detailed studies are warranted to utilize the broad spectrum of effects of individual compounds in future treatments.

The present article is aimed at determination of acid dissociation constants (pK_a), lipophilicity (logP) and hydrogen bond acceptor (HBA) and donor (HBD) counts of some novel xylene-linked bispyridiniumoxime based AChE reactivators. The choice was supported by their use in the therapy of acute intoxication with organophosphorus AChE inhibitors. UV-Vis spectrophotometry has been used to measure experimental pK_a values at 27°C, while software Marvin Sketch (chemaxon) has been used to estimate structure based computational pK_a, logP values and hydrogen bonding parameters. The results were compared with standard oximes (HI-6 and obidoxime) under similar conditions. All the calculated pK_a values lie in the range of 7.45-9.85 which is well in agreement with most of the oxime reactivators studied so far.

It is known that nerve agents are potent inhibitors of acetylcholinesterase (AChE), the enzyme responsible for the hydrolysis of the neurotransmitter acetylcholine and, thus, transmission of nerve impulses. The process of AChE inhibition by nerve agents can be reversed by a nucleophile able to dephosphorylate the enzyme. In this sense, oximes exhibit this characteristic and are able to remove the neurotoxic and reactivate AChE. Here, we review experimental and theoretical results involving docking and quantum mechanical-molecular mechanics hybrid methods (QM/MM), using Molegro^® and Spartan^® softwares to analyze the interaction of different nerve agents and oximes with AChE and to evaluate kinetic constants of reactivation.

Polymer drug delivery systems were during last few decades proven to be efficient potential therapeutics for cancer treatment, especilly for the treatment of solid tumors, where they may take advantage of the Enhanced Permeability and Retention (EPR) effect for tumor-specific passive accumulation. Controlled release of anticancer drugs in cancer cells may be triggered by. e.g., cathepsin B activation after endocytosis. Endosomal proteases, especially cathepsins B and L, are known to be one of the key factors influencing some viral infections. For instance Ebola virus requires partial proteolysis of its surface glycoprotein for efficient endosome escape within its life cycle. We hypothesize that polymeric cathepsin B and L inhibitors may utilize advantages of polymer delivery systems for more effective treatment of viral infections with cathepsin inhibitors reducing systemic toxicity and increasing efficacy by targeted delivery of these inhibitors.

Carbamates neurotoxins are a group of compounds acting as pseudo-irreversible inhibitors of an enzyme acetylcholinesterase and butyrylcholinesterase. The compounds are well known as pesticides. Some of them, such as rivastigmine, pyridostigmine, and neostigmine, can be used as drugs for Myasthenia gravis or Alzheimer disease as well. The present review is aimed to summarize the basic facts about carbamate pesticides. Legislative aspects, e.g. law No. 326/2004 Coll., in the Czech Republic and examples of accidental exposures to carbamates in the country are provided, too. Other general provisions are determined by the EU, in particular by the Directive 91/414/EHS. The European legislative is discussed, too. Finally, examples of accidental exposures are introduced in the study.

Aim: Cytokinesis-block micronucleus (CBMN) assay and its comprehensive variant CBMN cytome assay are cytogenetic methods. CBMN is based on assessment of micronuclei in nucleated cells that have completed only one nuclear division. Besides micronuclei, CBMN cytome assay analyzes additional genotoxic (nucleoplasmic bridges and nuclear buds), cytostatic (nuclear division index), and cytotoxic (amount of necrotic and apoptotic cells) parameters. The aim of this study is to evaluate these parameters in human blood lymphocytes after in vitro irradiation and to assess its contribution to biodosimetry. Material and methods: Human blood from 6 donors was in vitro irradiated by 0, 1, 2, 3, 4, or 5 Gy and cultivated for 72 hours. Blood lymphocytes were stimulated with phytohemagglutinin and their cytokinesis was blocked by cytochalasin B. After cultivation, cultures were hypotonically treated, dropped onto glass slides and stained with Giemsa. Slides were evaluated by microscope. Results: We observed significantly increased amount of micronuclei, nucleoplasmic bridges, and nuclear buds measured in binucleated cells, significantly increased amount of micronuclei measured in mononucleated cells and significantly decreased nuclear division index after irradiation by 1, 2, 3, 4, and 5 Gy. Amount of death cells (apoptotic and necrotic) significantly increased after irradiation by 4 and 5 Gy. Conclusion: Although all parameters assessed by CBMN cytome assay have biodosimetric potential, practically feasible is only evaluation of micronuclei in binucleated cells. This parameter was used to construct in vitro linear-quadratic dose-response calibration curve which could be used as a biodosimetric tool for triage of radiation casualties.

Kim Jong-nam (10 May 1971 - 13 February 2017) was the eldest son of Kim Jong-il, leader of North Korea, and the estranged half-brother of North Korean dictator Kim Jong-un. From roughly 1994 to 2001, he was considered the heir to his father [1]. Following a series of actions showing dissent to the North Korean regime, including a failed attempt to visit Tokyo Disneyland in May 2001 by entering Japan with a false passport, he was thought to have fallen out of favour with his father. On 13 February 2017, Kim was allegedly murdered by two women who fled after the crime [2]. The murder was commited in Malaysia during his return trip to Macau, at the low-cost carrier terminal of the Kuala Lumpur International Airport [3]. Initial reports suggest that Kim Jong-nam was murdered by VX, a type of agent used in chemical warfare [4]. Toxicological tests showed the presence of VX in Kim's eyes and face [5]. What is the agent VX and could this toxic substance cause the death of Kim?

Plasma proteins such as human serum albumin (HSA) and alpha 1-acid glycoprotein (AGP) play an important role in the pharmacokinetic and pharmacodynamic properties of all endogenous or exogenous substances presented in the blood vessels. Their abundance in human blood not only helps to maintain hemostasis, but also makes them ideal candidates as transporters or possible depot reservoirs. Numerous methods e.g. equilibrium dialysis, ultrafiltration. ultracentrifugation, high-performance affinity chromatography were introduced to determine potential interactions with plasma proteins and possible quantification.In this work method was developed for the determination of drug-human serum albumin interactions and applied to obtain pharmacokinetic profile of AChE modulators prepared at the Faculty of Military Health Sciences. For method validation commercially used compounds HI-6 and obidoxime were chosen. HI-6 did not bind at all while obidoxime showed 7 % binding potency.

Poisoning by organophosphates (OPs) takes one of the leading places in the total number of exotoxicoses. Detoxication of OPs at the first stage of poisoning could be achieved with the help of aptamers, which are able to bind poisons in the bloodstream [1]. The effectiveness of the aptamers for OPs could be strengthened by their possibility to bind non-covalently with the peripheral anionic site (PAS) of acetylcholinesterase (AChE) defending the active site gorge from OPs molecules. In the present work, we have applied for the first time the in silico design of a combined aptamer for paraoxon and PAS of AChE. Based on the published sequence of an aptamer binding organophosphorus pesticides [2], its three-dimensional model was constructed. The most probable binding site for paraoxon was determined by molecular docking and molecular dynamics (MD) methods. Then the nucleotides of the binding site were mutated consequently and the values of free binding energy were calculated using MD trajectories and MM-PBSA approach [3]. On the basis of the energy values, the sequences that bind paraoxon most efficiently have been selected. Molecular docking of sixteen possible nucleotide pairs into PAS of AChE was performed and the pairs that bind with PAS most efficiently have been selected. The 5’-end of the aptamers for paraoxon was modified based on the results of molecular docking. The calculations have shown that the final aptamers interact with paraoxon and PAS of AChE more efficiently than AChE interacts with paraoxon.

Pregnancy related maternal mortality defines the state of maternal health. The increasing incidence of maternal death in the U.S indicates that this complex issue is not unique only to developing countries.  It is obvious that improvements are needed to reinsure appropriate healthcare for all pregnant women.  Without precise methodical data collection and data evaluation advancement of this important determinant of maternal health can’t be achieved.The aim of this paper is to provide contemporary perspective on pregnancy related maternal mortality.  In addition, this paper will discuss common ethnical disparities that underline maternal deaths.  Furthermore, this paper will address the confusing inconsistencies of maternal death terminology and variations in disease classification.  Finally, this paper will propose improvements in defining terminology and data collection that influence the understanding of pregnancy related morbidity.Quick Points - 1. Maternal mortality is a determining characteristic of existing maternal health in a given geographical region. 2. While it is impossible to completely eliminate all maternal deaths, preventable pregnancy complications    resulting in injury or death need to be reduced across the world. 3. Healthcare leaders need to work on identification of maternal mortality trends and development

The interest and the increasing need for communication, exchange of experience and materials, training in diagnostics and research methods has led to the idea of creating an international scientific society focusing on tularemia. Tularemia meetings focus on fundamental, clinical, and applied research regarding any aspect of Francisella tularensis.  Research uncovers not only the biology of this fascinating bacterium, but also provides the basis for future development of treatments, preventive interventions, and disease diagnosis. Under the umbrella and with active participation of WHO, a group of scientists has met to develop this idea.

Evidence-Based Toxicology (EBT) was established in 2005 as a tool for toxicological risk assessment and causal link on the basis of the parallel relationship between the toxicological test method evaluation and the Evidence-Based Diagnostic Testing Assessment (EBM). The introduction of evidence-based principles can provide new tools that are necessary to validate toxicological testing methods. EBT should contribute to testing strategies to address toxicology problems in the 21^st century. Practice has shown that the underlying concepts of EBT, such as the use of systematic reviews to capture and consider all available information, improve the results of toxicological assessment conducted by different groups and orga-nizations. New challenges are emerging before toxicology, such as safety assessments of new agrochemicals, pharmaceuticals and nanomaterials, and EBT can provide important results for their application in practice.

Perfluoroisobutene (PFIB) is a colorless toxic gas which can be absorbed into the body by inhalation. The substance irritates the respiratory tract and may be used as a potential chemical warfare agent.  Inhalation exposure may cause severe symptoms of pulmonary edema associated with wheezing, difficulty in breathing and sputum expectoration. A bluish skin color is also observed. Initially, cough and chest pain may occur. However, severe symptoms of pulmonary edema may be delayed for several hours before a rapid deterioration of health occurs. Excessive exposure may cause death.

Exsanguination is one of the leading causes of death in a battlefield. Patients who require cardiopulmonary resuscitation after moribund trauma have an unfavorable prognosis. The determinant of survival in critically injured is a time to surgical intervention. Resuscitative emergency thoracotomy may be the lifesaving treatment in selected patients with trunk trauma and cardiac arrest after hemorrhagic shock.This is a case report of successfully applied resuscitative surgical techniques in severely injured allied soldier with hemorrhagic shock and cardiac arrest after suicide bomber explosion. A prompt diagnosis and a rapid emergency thoracotomy are lifesaving in moribund penetrating or blunt trunk trauma.

Internal medical disciplines (internal medicine and other internal specialties) are among the key clinical branches for the Ministry of Defence and the military medical service. The work provides an overview of the current state of internal medical disciplines within the Ministry of Defence. The main problem is the lack of qualified medical personnel and a complicated system of specialized training due to complexity of these fields. The results section provides options for the further development of internal medical disciplines to secure fulfilment of tasks of military medical service in favour of the Ministry of Defence, in the field of therapeutic-preventive, pedagogical-educational and scientific-research. Internal medicine is a fundamental branch of military health care and the model of a possible development way of one discipline is applicable also to other medical disciplines.

Introduction: Metabolic changes induced by stress reaction are, among other things, characterized by increased turnover of non-esterified fatty acids (NEFA), which results in an increase in their plasma concentration. The aim of the study was to determine how intravenous nutritional support (TPN) will affect the concentration of NEFA in critically ill individuals. Methods: 38 patients in averaged 65 ± 11 years old hospitalized in a medical intensive care unit of university hospital in years 2015-2018 were examined. They were given isocaloric (30 kcal/kg/day) and isonitrogenic (1.8 g/kg/day) TPN in combination with glucose (5.8 g/kg/day; glucose group, G) or in combination with glucose (2.9 g/kg/day) and lipid emulsion (1.2 g/kg/day; lipid group, L). NEFA measurements were performed before starting TPN (day 0) and then at days 1, 3, 6, 9, 14 and 28 using enzymatic and spectrophotometric method. Statistical program Jamovi and the Mann-Whitney U test were used. Results: There was no significant difference in NEFA concentration (mmol/L) at day 0 (G 0.502 ± 0.291, L 0.409 ± 0.126). There was significant decrement (p < 0.001) in day 1 (G 0.220 ± 0.112, L 0.279 ± 0.126). When comparing both groups decrease was more significant in the G, and statistical significance (p < 0.05) was achieved at days 6, 9, 14 and 28. Conclusion: Starting of TPN results in a decrease of NEFA concentration with a greater effect at a higher glucose dose. Glucose administration is able to modify NEFA turnover in critical illness.

Many unfavourable factors can affect decontamination efficacy when personnel wearing personal protective equipment are decontaminated prior to their final exit from the hot zone. One of the most important factors is the quality of aerosol, which is determined mainly by the size and amount of droplets. Aerosol quality is closely related to the target area coverage efficacy or to deflection of droplets from the direction of flight, so called drift. Studies comparing, e.g., droplet size, velocity, trajectory, spray height, viscosity, surface tension, and wind speed are scarce. The quality of spraying and its application have been intensively studied by agricultural research since the 1950s. Although this research has specific characteristics, it can provide important guidance for the decontamination of high-risk biological pathogens.

The case report presents a case of a very rare anomaly of bile ducts. A 57-year-old patient underwent elective laparoscopic cholecystectomy. The double duct cysticus was the reason of conversion to open surgery. The findings was confirmed due perioperative cholangiography and histological conclusion. This rare abnormality can cause serious surgical accidents. We present our case to point out possible risks of routine laparoscopic cholecystectomy.

Group of viral hemorrhagic fevers (VHF) present a range of disorders from relatively moderately serious to human life threatening entities whose mortality reaches high levels. There are classified as acute viral febrile diseases characterized by nausea, myalgia and fatigue, dominating with general alteration of vessel permeability and regulation. Symptoms of bleeding often occur, particularly in severe cases which are usually diffuse and present a symptom of general vessel injury rather than life-threatening condition.

Viral hemorrhagic fevers (VHFs) represent a collection of illnesses caused by several distinct viral families. While some types of hemorrhagic fever viruses can cause relatively mild illnesses, many of these viruses cause life-threatening diseases. In general, the term "viral hemorrhagic fever" describes a severe multisystem syndrome. Typical for this syndrome is a systemic damage of vascular system often accompanied by hemorrhages.Ebola is a type of VHF, along with Marburg, Lassa, dengue, Rift Valley, and yellow fever. VHFs are RNA viruses whose survival is dependent on animal or insect hosts. Ebola hemorrhagic fever initially makes the leap from an animal reservoir to a human, and can then be passed from human to human through direct contact.In the autumn and winter of 2014 every day professional and popular press published new information about Ebola outbreak in West Africa. It was not just data related to the number of patients, new recommendations and protocols, information about testing of potential vaccines, but also theoretical works that tried to analyze the situation and data.

Deoxynivalenol (DON) is a trichothecene mycotoxin regularly occurring in cereals. It is toxic to humans and inhibits DNA, RNA and protein synthesis. Moreover, its conjugated products, called masked mycotoxins, including DON-3-glucoside (DON-3G), is another "emerging" food safety issue in recent years. In this review, we first discussed the nature of contamination of masked DON in cereal-based food and feed; moreover, the new reported masked DON is summarized and we also focused on its toxicity and digestion in human and animal bodies. In addition, the contamination of DON in cereal-based feed in different countries was summarized and some regular patterns of DON occurrence are suggested. Finally, the LC-MS methods for the determination of DON and masked DON in food, feed and animal fluids were compared. This review will provide further information for DON and masked DON contamination and shed some light on the mycotoxin control strategies.

International terrorism becomes one of the most dangerous problems at the beginning of the 21^st century. Terrorist attacks have serious impact on politics, economy, military as well as security forces, international law and legislation, and psychological issues. International terrorism is legally characterised not only as a threat to the life and property of individuals, but also as a worldwide threat to human civilization, social order, international public order and values. The aim of this contribution is to specify the incidence of terrorist attacks from 1970 to 2013 in European countries and to characterise their imminent impact on the number of casualties. Furthermore, the contribution aims to specify the type of these attacks, weapons employed in them and numbers of casualties corresponding to various types of weapons. The analysis was based on data from databases and existing studies. The monitored period witnessed a slow but steady increase in the incidence of terrorist attacks in the EU countries without any significant changes. The types of weapons employed in these attacks did not change much, either.

Healthcare is an industry that has a very strong position in economies and a relatively high share of GDP. It also includes the medical device industry. The aim of this paper is to analyse the potential of the market for medical devices in Europe. The starting point is the analysis of the external environment, describing the selected macroeconomic variables affecting aggregate demand and therefore the medical device industry in selected countries. The tool for strategic analysis of the European market is Porter's Five Forces model, where initial information is obtained from the analysis of economic indicators of the given industry, analysis of world databases data, analysis of documents dealing with studies of the medical device industry.The European market can be described as highly competitive, with a large number of small and medium-sized companies, stable innovative activity, which is significantly defined by the regulations by the competent authorities. Globally, this industry is predicted to grow.