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Petra Maresova,1 Jan Hruška,1 Kristina Randlova,1,2 Lukas Rezny,1,3 María Teresa Carrillo-de-la-Peña,4 Kamil Kuca1,3 1Betthera S.r.o., Hradec Kralove, Czech Republic; 2Prague University of Economics and Business, Faculty of Management, Department of Management, Prague, Czech Republic; 3University of Hradec Kralove, Faculty of Informatics and Management, Department of Economics, Hradec Kralove, Czech Republic; 4University of Santiago de Compostela, Department of Clinical Psychology and Psychobiology, A Coruña, SpainCorrespondence: Kamil Kuca, Email kuca@betthera.comBackground: The increased prevalence of cancer and the negative impact of pain on the quality of life of patients underscore the need to implement efficient palliative care interventions and management of pain. The cost-effectiveness of palliative care interventions for cancer, mostly pharmacological and delivered through home-based palliative care services, is unclear. Most of the studies do not take into account indirect costs nor consider variations across different geographical regions.Objective: To describe existing and cutting-edge knowledge on cost-effectiveness or item costs related to palliative home-based care for patients with cancer. We evaluated various costs, including direct medical, non-medical, and indirect costs in different geographical regions and analysed how different options for care affect the patients’ quality of life and associated expenses.Methods: This Prospero-registered systematic review (CRD42023404217) adhered to the PRISMA criteria. Following a multistep selection process, we selected 22 articles published between 2013 and 2023 focused on quality of life outcomes and cost-effectiveness of home-based palliative care for cancer patients.Results: Home-based palliative care decreases the number of hospital visits, while its influence on patients quality of life is currently difficult to demonstrate across geographic regions based on available evidence. Overall, home care decreases the costs associated to the palliative care of patients with cancer. The cost structure analysis revealed that besides healthcare costs, informal care expenses and productivity losses represent a significant proportion of overall expenses). In Europe, the direct medical, non-medical, and indirect costs (in purchasing power parity) were on average $1,941, $842, and $1,241, per month per person, respectively. In the USA and Asia, direct medical and indirect costs are on average $1,095 (USA) vs $1,444 (Asia) and $2,192 (USA) vs $1,162 (Asia).Conclusion: In conclusion, the studies reviewed highlight significant cost variations and potential savings associated with palliative home-based care for cancer patients. Home-based palliative care, particularly involving medications, has shown favorable cost-effectiveness compared to hospital care. Specialized palliative home care, psychological interventions, and outpatient services further contribute to overall cost savings. However, the economic impact varies across different geographical contexts and cost categories, emphasizing the need for tailored approaches in palliative care planning and implementation.Keywords: cost-effectiveness, palliative care, treatment, interventions, review, pain management, cancer, quality of life

Mostafa Yusefi,1,2 Kamyar Shameli,3 Hossein Jahangirian,4 Sin-Yeang Teow,5 Leili Afsah-Hejri,6 Siti Nur Amalina Mohamad Sukri,1 Kamil Kuča1,7,8 1Malaysia-Japan International Institute of Technology, Universiti Teknologi Malaysia, Kuala Lumpur, Malaysia; 2Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur, 50603, Malaysia; 3Institute of Virology, School of Medicine, Technical University of Munich, Munich, 81675, Germany; 4CaroGen Corporation, Farmington, CT, USA; 5Department of Biology, College of Science, Mathematics and Technology, Wenzhou-Kean University, Wenzhou, Zhejiang Province, 325060, People’s Republic of China; 6Department of Food Safety and Quality, School of Business, Science and Technology, Lakeland University Plymouth, WI 53073, USA; 7Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic; 8Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech RepublicCorrespondence: Kamyar Shameli; Hossein Jahangirian, Tel +4917646555701 ; +16178608429, Email kamyarshameli@gmail.com; kamran.jahangirian@gmail.comAbstract: Chemotherapy is the most prominent route in cancer therapy for prolonging the lifespan of cancer patients. However, its non-target specificity and the resulting off-target cytotoxicities have been reported. Recent in vitro and in vivo studies using magnetic nanocomposites (MNCs) for magnetothermal chemotherapy may potentially improve the therapeutic outcome by increasing the target selectivity. In this review, magnetic hyperthermia therapy and magnetic targeting using drug-loaded MNCs are revisited, focusing on magnetism, the fabrication and structures of magnetic nanoparticles, surface modifications, biocompatible coating, shape, size, and other important physicochemical properties of MNCs, along with the parameters of the hyperthermia therapy and external magnetic field. Due to the limited drug-loading capacity and low biocompatibility, the use of magnetic nanoparticles (MNPs) as drug delivery system has lost traction. In contrast, MNCs show higher biocompatibility, multifunctional physicochemical properties, high drug encapsulation, and multi-stages of controlled release for localized synergistic chemo-thermotherapy. Further, combining various forms of magnetic cores and pH-sensitive coating agents can generate a more robust pH, magneto, and thermo-responsive drug delivery system. Thus, MNCs are ideal candidate as smart and remotely guided drug delivery system due to a) their magneto effects and guide-ability by the external magnetic fields, b) on-demand drug release performance, and c) thermo-chemosensitization under an applied alternating magnetic field where the tumor is selectively incinerated without harming surrounding non-tumor tissues. Given the important effects of synthesis methods, surface modifications, and coating of MNCs on their anticancer properties, we reviewed the most recent studies on magnetic hyperthermia, targeted drug delivery systems in cancer therapy, and magnetothermal chemotherapy to provide insights on the current development of MNC-based anticancer nanocarrier.Keywords: magnetic nanoparticles, polymer-based magnetic nanocomposites, hyperthermia, external magnetic field, targeted cancer treatments

Mostafa Yusefi,1 Kamyar Shameli,1 Ong Su Yee,1 Sin-Yeang Teow,2 Ziba Hedayatnasab,3,4 Hossein Jahangirian,5 Thomas J Webster,5 Kamil Kuča1,6 1Department of Chemical and Environmental Engineering, Malaysia-Japan International Institute of Technology, Universiti Teknologi Malaysia, Kuala Lumpur, 54100, Malaysia; 2Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Petaling Jaya, Selangor Darul Ehsan, 47500, Malaysia; 3Department of Chemical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur, 50603, Malaysia; 4Department of Chemical and Petroleum Engineering, Sharif University of Technology, Tehran, 11155-9465, Iran; 5Department of Chemical Engineering, College of Engineering, Northeastern University, Boston, MA, 02115, USA; 6Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech RepublicCorrespondence: Kamyar Shameli; Kamil Kuča Email kamyarshameli@gmail.com; kamil.kuca@uhk.czIntroduction: Fe3O4 nanoparticles (Fe3O4 NPs) with multiple functionalities are intriguing candidates for various biomedical applications.Materials and Methods: This study introduced a simple and green synthesis of Fe3O4 NPs using a low-cost stabilizer of plant waste extract rich in polyphenols content with a well-known antioxidant property as well as anticancer ability to eliminate colon cancer cells. Herein, Fe3O4 NPs were fabricated via a facile co-precipitation method using the crude extract of Garcinia mangostana fruit peel as a green stabilizer at different weight percentages (1, 2, 5, and 10 wt.%). The samples were analyzed for magnetic hyperthermia and then in vitro cytotoxicity assay was performed.Results: The XRD planes of the samples were corresponding to the standard magnetite Fe3O4 with high crystallinity. From TEM analysis, the green synthesized NPs were spherical with an average size of 13.42± 1.58 nm and displayed diffraction rings of the Fe3O4 phase, which was in good agreement with the obtained XRD results. FESEM images showed that the extract covered the surface of the Fe3O4 NPs well. The magnetization values for the magnetite samples were ranging from 49.80 emu/g to 69.42 emu/g. FTIR analysis verified the functional groups of the extract compounds and their interactions with the NPs. Based on DLS results, the hydrodynamic sizes of the Fe3O4 nanofluids were below 177 nm. Furthermore, the nanofluids indicated the zeta potential values up to − 34.92± 1.26 mV and remained stable during four weeks of storage, showing that the extract favorably improved the colloidal stability of the Fe3O4 NPs. In the hyperthermia experiment, the magnetic nanofluids showed the acceptable specific absorption rate (SAR) values and thermosensitive performances under exposure of various alternating magnetic fields. From results of in vitro cytotoxicity assay, the killing effects of the synthesized samples against HCT116 colon cancer cells were mostly higher compared to those against CCD112 colon normal cells. Remarkably, the Fe3O4 NPs containing 10 wt.% of the extract showed a lower IC50 value (99.80 μg/mL) in HCT116 colon cancer cell line than in CCD112 colon normal cell line (140.80 μg/mL).Discussion: This research, therefore, introduced a new stabilizer of Garcinia mangostana fruit peel extract for the biosynthesis of Fe3O4 NPs with desirable physiochemical properties for potential magnetic hyperthermia and colon cancer treatment.Keywords: green synthesis, Fe3O4 nanoparticles, Garcinia mangostana, magnetic hyperthermia, cytotoxicity assay

Petra Maresova,1 Michal Novotny,2,3 Blanka Klímová,4 Kamil Kuča3,51Department of Economics, Faculty of Informatics and Management, 2Department of Chemistry, Faculty of Science, University of Hradec Králové, 3Biomedical Research Center, University Hospital Hradec Králové, 4Department of Applied Linguistics, Faculty of Informatics and Management, 5Faculty of Informatics and Management, University of Hradec Králové, Hradec Králové, Czech Republic Background: Narcolepsy is a lifelong, rare neurological sleep disorder characterized by chronic, excessive attacks of daytime sleepiness. This disease is often extremely incapacitating, interfering with every aspect of life, in work and social settings.Objective: The purpose of this study is to specify the treatment costs of patients in the Central Europe (Czech Republic), while the attention is mainly paid to the drugs that were fully or partially covered by public health insurance. Furthermore, concomitant therapy is also evaluated, since it incurs a certain financial burden for patients and their family members. On the basis of the calculated costs, impact on the public budget is evaluated.Patients and methods: This study monitors the direct costs of the drugs for 13 patients, who represent ~1.3% of the total number of diagnosed patients in the Czech Republic, and evaluates the costs associated with their treatment during the period from January 9, 2011 to April 23, 2013.Results: Most of the treatment costs (~80%) were covered by publicly available sources. This finding is also true for the concomitant therapy of comorbidities. Additional payments for the drugs constitute about 20% of the total costs. Keywords: cataplexy, cost, narcolepsy, orphan drug, rare disease, sodium oxybate

Marek Bužga,1 Petra Maresova,2 Adela Seidlerová,1 Pavel Zonča,1 Pavol Holéczy,1 Kamil Kuča2,3 1Research Obesity Center, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic; 2Faculty of Informatics and Management, University of Hradec Kralove, Hradec Kralove, Czech Republic; 3Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic Abstract: The constantly growing incidence of obesity represents a risk of health complications for individuals, and is a growing economic burden for health care systems and society. The aim of this study was to evaluate the efficacy of bariatric surgery, specifically laparoscopic greater curve plication, laparoscopic sleeve gastrectomy, and Roux-en-Y gastric bypass, in patients with type 2 diabetes mellitus. The effect of bariatric surgery on the changes in blood pressure before, and 12 months after, surgery and in pharmacotherapy in the 12 months after surgery was analyzed. For achieving this purpose, 74 patients from the Obesity and Surgery Department of Vitkovice Hospital in Ostrava in the Czech Republic, were monitored. They were operated in 2011 and 2012. The Bonferroni method was used to test hypotheses about the impact of surgery on blood pressure and pharmacotherapy. One year after the surgery, systolic and diastolic blood pressure values decreased, both with no statistically significant difference between surgery types. Improvement was observed in 68% of cases, with 25% of patients discontinuing pharmacotherapy entirely. Keywords: type 2 diabetes mellitus, bariatric surgery, blood pressure, pharmacotherapy

With continued climate changes, soil drought stress has become the main limiting factor for crop growth in arid and semi‐arid regions. A typical characteristic of drought stress is the burst of reactive oxygen species (ROS), causing oxidative damage. Plant‐associated microbes, such as arbuscular mycorrhizal fungi (AMF), can regulate physiological and molecular responses to tolerate drought stress, and they have a strong ability to cope with drought‐induced oxidative damage via enhanced antioxidant defence systems. AMF produce a limited oxidative burst in the arbuscule‐containing root cortical cells. Similar to plants, AMF modulate a fungal network in enzymatic (e.g. GmarCuZnSOD and GintSOD1) and non‐enzymatic (e.g. GintMT1, GinPDX1 and GintGRX1) antioxidant defence systems to scavenge ROS. Plants also respond to mycorrhization to enhance stress tolerance via metabolites and the induction of genes. The present review provides an overview of the network of plant − arbuscular mycorrhizal fungus dialogue in mitigating oxidative stress. Future studies should involve identifying genes and transcription factors from both AMF and host plants in response to drought stress, and utilize transcriptomics, proteomics and metabolomics to clarify a clear dialogue mechanism between plants and AMF in mitigating oxidative burst. [ABSTRACT FROM AUTHOR]

Daljeet Singh Dhanjal,1,* Parul Mehra,2,* Sonali Bhardwaj,1,* Reena Singh,1 Parvarish Sharma,3 Eugenie Nepovimova,4 Chirag Chopra,1 Kamil Kuca4,5 1School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, India; 2Central Research Institute, Kasauli, Himachal Pradesh, India; 3School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India; 4Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, 50003, Czech Republic; 5Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, 50005, Czech Republic*These authors contributed equally to this workCorrespondence: Kamil Kuca, Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, 50003, Czech Republic, Tel +420 603 289 166, Email kamil.kuca@uhk.cz Chirag Chopra, School of Bioengineering and Biosciences, Lovely Professional University, Jalandhar-Delhi GT Road, Phagwara, Punjab, 144411, India, +91-7837815676, Email chirag.18298@lpu.co.inAbstract: In today’s time, nanotechnology is being utilized to develop efficient products in the cosmetic and pharmaceutical industries. The application of nanotechnology in transforming bioactive material into nanoscale products substantially improves their biocompatibility and enhances their effectiveness, even when used in lower quantities. There is a significant global market potential for these nanoparticles because of which research teams around the world are interested in the advancements in nanotechnology. These recent advances have shown that fungi can synthesize metallic nanoparticles via extra- and intracellular mechanisms. Moreover, the chemical and physical properties of novel metallic nanoparticles synthesised by fungi are improved by regulating the surface chemistry, size, and surface morphology of the nanoparticles. Compared to chemical synthesis, the green synthesis of nanoparticles offers a safe and sustainable approach for developing nanoparticles. Biosynthesised nanoparticles can potentially enhance the bioactivities of different cellular fractions, such as plant extracts, fungal extracts, and metabolites. The nanoparticles synthesised by fungi offer a wide range of applications. Recently, the biosynthesis of nanoparticles using fungi has become popular, and various ways are being explored to maximize nanoparticles synthesis. This manuscript reviews the characteristics and applications of the nanoparticles synthesised using the different taxa of fungi. The key focus is given to the applications of these nanoparticles in medicine and cosmetology.Keywords: fungi, biological application, biosynthesis, nanoparticles, nanotechnology

Sarka Salajkova,1,2 Filip Havel,1,3 Michal Sramek,1 Filip Novotny,1,4 David Malinak,2,5 Rafael Dolezal,2,5 Lukas Prchal,2 Marketa Benkova,2 Ondrej Soukup,2 Kamil Musilek,2,5 Kamil Kuca,2,5 Jiri Bartek,1,6,7 Jan Proska,3 Monika Zarska,1 Zdenek Hodny1 1Department of Genome Integrity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic; 2Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic; 3Department of Physical Electronics, Faculty of Nuclear Sciences and Physical Engineering, Czech Technical University in Prague, Prague, Czech Republic; 4Center for Advanced Functional Nanorobots, Department of Inorganic Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology Prague, Prague, Czech Republic; 5Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic; 6Genome Integrity Unit, Danish Cancer Society Research Center, Copenhagen, Denmark; 7Department of Medical Biochemistry and Biophysics, Science for Life Laboratory, Division of Genome Biology, Karolinska Institute, Stockholm, SwedenCorrespondence: Monika ZarskaDepartment of Genome Integrity, Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska 1083, Prague 4, Prague, CZ 142 20, Czech RepublicTel +420- 24106 3151Fax + 420-24106 2289Email monika.zarska@img.cas.czKamil KucaBiomedical Research Center, University Hospital Hradec Kralove, Sokolska 581, Hradec Kralove, CZ 500 05, Czech RepublicTel +420-495 833 447Email kamil.kuca@fnhk.czPurpose: Plasmonic photothermal cancer therapy by gold nanorods (GNRs) emerges as a promising tool for cancer treatment. The goal of this study was to design cationic oligoethylene glycol (OEG) compounds varying in hydrophobicity and molecular electrostatic potential as ligand shells of GNRs. Three series of ligands with different length of OEG chain (ethylene glycol units = 3, 4, 5) and variants of quaternary ammonium salts (QAS) as terminal functional group were synthesized and compared to a prototypical quaternary ammonium ligand with alkyl chain – (16-mercaptohexadecyl)trimethylammonium bromide (MTAB).Methods: Step-by-step research approach starting with the preparation of compounds characterized by NMR and HRMS spectra, GNRs ligand exchange evaluation through characterization of cytotoxicity and GNRs cellular uptake was used. A method quantifying the reshaping of GNRs was applied to determine the effect of ligand structure on the heat transport from GNRs under fs-laser irradiation.Results: Fourteen out of 18 synthesized OEG compounds successfully stabilized GNRs in the water. The colloidal stability of prepared GNRs in the cell culture medium decreased with the number of OEG units. In contrast, the cellular uptake of OEG+GNRs by HeLa cells increased with the length of OEG chain while the structure of the QAS group showed a minor role. Compared to MTAB, more hydrophilic OEG compounds exhibited nearly two order of magnitude lower cytotoxicity in free state and provided efficient cellular uptake of GNRs close to the level of MTAB. Regarding photothermal properties, OEG compounds evoked the photothermal reshaping of GNRs at lower peak fluence (14.8 mJ/cm2) of femtosecond laser irradiation than the alkanethiol MTAB.Conclusion: OEG+GNRs appear to be optimal for clinical applications with systemic administration of NPs not-requiring irradiation at high laser intensity such as drug delivery and photothermal therapy inducing apoptosis.Keywords: gold nanorods, quaternary ammonium salts, oligoethylene glycol, cellular uptake, photothermal stability

Blanka Klimova,1 Michal Novotný,2 Kamil Kuca,2–4 Martin Valis5 1Department of Applied Linguistics, University of Hradec Kralove, Hradec Kralove 500 03, Czech Republic; 2Biomedical Research Centre, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic; 3Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic; 4Malaysia Japan International Institute of Technology (MJIIT), Universiti Teknologi Malaysia Kuala Lumpur, Jalan Sultan Yahya Petra, Kuala Lumpur 54100, Malaysi; 5Department of Neurology, University Hospital Hradec Kralove, Hradec Kralove 500 05, Czech RepublicCorrespondence: Kamil KucaUniversity Hospital, Sokolska 581, Hradec Kralove, Czech RepublicTel +420 603 289 166Fax +420 495 835 200Email kamil.kuca@fnhk.czAbstract: Currently, there is an increase in the number of the world’s aging population. This aging process is often connected with cognitive decline of some functions such as memory or speed processing loss. Since Alzheimer’s disease cannot be cured yet, considerable efforts are being made to at least delay this cognitive decline among elderly in order to maintain and prolong the quality of their life. This can also be achieved by non-pharmacological approaches such as performing physical activities, cognitive training, or adhering to a Mediterranean Diet (MedDiet). One of the components of MedDiet – extra-virgin olive oil (EVOO) – has considerable health benefits. The purpose of this review is to examine the effect of EVOO intake on the delay of cognitive decline among the elderly. The methodology is based on a literature review of available sources found on the research topic in three acknowledged databases: Web of Science, Scopus, and PubMed. The results of in vitro and in vivo studies indicate that the regular intake of EVOO is associated with enhanced cognitive functions, which means that this oil may have a neuroprotective effect and could positively prevent the development of dementia, especially Alzheimer’s dementia. It is believed that secoiridoid oleuropein is responsible for this effectiveness. Furthermore, there is also a need of more randomized controlled studies or longitudinal observational studies to be performed to confirm the efficacy of the beneficial health effect of EVOO on the delay of cognitive decline.Keywords: extra-virgin olive oil, oleuropein, oleuropein-aglycone, cognitive decline, Alzheimer disease, review

Blanka Klimova,1 Martin Valis,2 Kamil Kuca3 1Department of Applied Linguistics, Faculty of Informatics and Management, University of Hradec Kralove, Hradec Kralove, Czech Republic; 2Department of Neurology, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic; 3Centre for Basic and Applied Research, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic Abstract: Nowadays, due to the increase in the number of aging population groups, there is also a growth of aging diseases such as Alzheimer’s disease (AD), which is a progressive brain disorder that eventually results in death. At the moment, it cannot be cured, only its symptoms can be alleviated both by using pharmacological and non-pharmacological approaches in order to maintain and in some cases even enhance quality of life of people living with AD, as well as their caregivers. One of such non-pharmacological approaches is the use of assistive technology (AT), which can contribute to the improvement and maintenance of the quality of life of both patients and their caregivers. The purpose of this study was to explore what types of AT are mostly used by patients with AD and how these devices can help their caregivers. This was done by conducting a literature review of available sources found in the Web of Science, Scopus, and PubMed. The findings, apart from one study, reveal that AT may have the potential to maintain the quality of life of people with AD, especially in the early stages of the disease, as well as to mitigate the mental and physical burden of their caregivers. The most common types of AT for patients with AD are devices of daily living and safety devices. The less frequent are still telecare devices and devices to support engagement, social participation, and leisure. Future research should focus on the effectiveness of AT on the improvement of patients’ symptoms, as well as on the development and use of AT for social interactions, which can be used in patients with AD of different degree of severity and have a positive impact on their behavioral and psychological symptoms. Keywords: assistive technology, Alzheimer’s disease, patients, caregivers, benefits

Jakub Jirka,1 Michal Prauzek,1 Ondrej Krejcar,2 Kamil Kuca2,3 1Department of Cybernetics and Biomedical Engineering, Faculty of Electrical Engineering and Computer Science, VSB – Technical University of Ostrava, Ostrava Poruba, Czech Republic; 2Center for Basic and Applied Research, Faculty of Informatics and Management, University of Hradec Kralove, Hradec Kralove, Czech Republic; 3Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic Objective: The most important part of signal processing for classification is feature extraction as a mapping from original input electroencephalographic (EEG) data space to new features space with the biggest class separability value. Features are not only the most important, but also the most difficult task from the classification process as they define input data and classification quality. An ideal set of features would make the classification problem trivial. This article presents novel methods of feature extraction processing and automatic epilepsy seizure classification combining machine learning methods with genetic evolution algorithms.Methods: Classification is performed on EEG data that represent electric brain activity. At first, the signal is preprocessed with digital filtration and adaptive segmentation using fractal dimensions as the only segmentation measure. In the next step, a novel method using genetic programming (GP) combined with support vector machine (SVM) confusion matrix as fitness function weight is used to extract feature vectors compressed into lower dimension space and classify the final result into ictal or interictal epochs.Results: The final application of GP–SVM method improves the discriminatory performance of a classifier by reducing feature dimensionality at the same time. Members of the GP tree structure represent the features themselves and their number is automatically decided by the compression function introduced in this paper. This novel method improves the overall performance of the SVM classification by dramatically reducing the size of input feature vector.Conclusion: According to results, the accuracy of this algorithm is very high and comparable, or even superior to other automatic detection algorithms. In combination with the great efficiency, this algorithm can be used in real-time epilepsy detection applications. From the results of the algorithm’s classification, we can observe high sensitivity, specificity results, except for the Generalized Tonic Clonic Seizure (GTCS). As the next step, the optimization of the compression stage and final SVM evaluation stage is in place. More data need to be obtained on GTCS to improve the overall classification score for GTCS. Keywords: genetic programming, adaptive segmentation, SVM, fractal dimensions, EEG

Kamil Kuca,1,2 Jana Zdarova Karasova,2,3 Ondrej Soukup,2 Jiri Kassa,3 Eva Novotna,2 Vendula Sepsova,2,3 Anna Horova,2 Jaroslav Pejchal,3 Martina Hrabinova,2,3 Eva Vodakova,2 Daniel Jun,2,3 Eugenie Nepovimova,1,2 Martin Valis,4 Kamil Musilek1,2 1Department of Chemistry, Faculty of Science, University of Hradec Kralove, 2Biomedical Research Center, University Hospital Hradec Kralove, 3Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defence, 4Department of Neurology, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic Background: Intoxication by nerve agents could be prevented by using small acetylcholinesterase inhibitors (eg, pyridostigmine) for potentially exposed personnel. However, the serious side effects of currently used drugs led to research of novel potent molecules for prophylaxis of organophosphorus intoxication. Methods: The molecular design, molecular docking, chemical synthesis, in vitro methods (enzyme inhibition, cytotoxicity, and nicotinic receptors modulation), and in vivo methods (acute toxicity and prophylactic effect) were used to study bispyridinium, bisquinolinium, bisisoquinolinium, and pyridinium-quinolinium/isoquinolinium molecules presented in this study. Results: The studied molecules showed non-competitive inhibitory ability towards human acetylcholinesterase in vitro that was further confirmed by molecular modelling studies. Several compounds were selected for further studies. First, their cytotoxicity, nicotinic receptors modulation, and acute toxicity (lethal dose for 50% of laboratory animals [LD50]; mice and rats) were tested to evaluate their safety with promising results. Furthermore, their blood levels were measured to select the appropriate time for prophylactic administration. Finally, the protective ratio of selected compounds against soman-induced toxicity was determined when selected compounds were found similarly potent or only slightly better to standard pyridostigmine. Conclusion: The presented small bisquaternary molecules did not show overall benefit in prophylaxis of soman-induced in vivo toxicity. Keywords: AChE inhibitors, prophylaxis, pre-treatment, nerve agents, toxicity, soman

Blanka Klimova,1,2 Martin Valis,2 Kamil Kuca3,4 1Department of Applied Linguistics, Faculty of Informatics and Management, University of Hradec Kralove, 2Department of Neurology, 3Biomedical Research Centre, University Hospital Hradec Kralove, 4Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic Abstract: The purpose of this study is to explore original studies which provide evidence about the effects of bilingualism on the delay of the onset of dementia, specifically Alzheimer’s disease (AD). A literature review was conducted in the world’s acknowledged databases: Web of Science, Scopus, and MEDLINE. Altogether, 14 original studies focusing on the research topic were detected. These included six prospective cohort studies and eight retrospective studies. Both types of studies suggest different conclusions. The findings from the prospective cohort studies state that there is no association between bilingualism and the delay of the onset of AD, while the retrospective studies claim the opposite. Despite the negative results of the prospective cohort studies, more research should be conducted on bilingualism and its impact on the delay of the onset of AD, since the brain studies have brought positive findings as far as the enhancement of cognitive reserve is concerned. Keywords: older people, evidence, effectiveness, review, cognition

Colorimetric dipsticks based on recognition capability of acetylcholinesterase enzyme (AChE) are a suitable tool for a fast and sensitive detection of nerve agents and some pesticides. In this review, the detectors are digestedly presented and basic biochemical methods appropriate for the colorimetric estimation of AChE enzymatic activity are included as well. Moreover, the available matrices suitable for construction of dipsticks and chemical, as well as physical protocols for AChE immobilization on detectors surface are introduced. [ABSTRACT FROM AUTHOR]

Oximes are cholinesterase reactivators used in organophosphorus poisoning. Clinical experience with pralidoxime (PRX) and other oximes is disappointing and their routine use has been questioned. In addition it is known that not all oximes are equally effective against all existing organophosphorus compounds. There is a demand for broad-spectrum reactivators with a higher efficacy than PRX. Based on our previous in vitro work the protection conferred by the various new oximes against inhibition by paraoxon as quantified by the IC50 shift (n m increase in the IC50 of the inhibitor per µ m oxime present) is: 0.3 (PRX), 0.4 (methoxime; MMC-4), 1 (K-33), 1.2 (BI-6), 1.5 (K-48) and 3.7 (K-27). The purpose of the study was to quantify in vivo the extent of oxime-conferred protection, using paraoxon (POX) as a cholinesterase inhibitor and to test whether in vitro efficacy translates to protection from mortality. There were seven groups of six rats in each cycle of the experiment. Group 1 (G1) received 1 µmol POX (≈ LD75), the other groups (G2-G7) received 1 µmol POX + of one the six reactivators. The animals were monitored for 48 h and the time of mortality was recorded. The procedure was repeated five times (cycles). All substances were applied i.p. The experiments were repeated using 2, 3, 5 and 10 µmol POX. Mortality data were compared and hazards ratios (relative risks) ranked using the Cox proportional hazards model using POX dose and group (reactivator) as time-independent covariables. The relative risk of death estimated by Cox analysis (95% CI) in oxime treated animals when compared with untreated animals, adjusted for POX dose (high/low) was K-27: 0.26 (0.19-0.35); K-48: 0.34 (0.25-0.45); methoxime: 0.38 (0.29-0.50); BI-6: 0.53 (0.41-0.69); PRX: 0.70 (0.54-0.91); K-33: 0.82 (0.63-1.07). It is concluded that K-27 and K-48 are the most promising new oximes. The compounds with the best results in vitro also confer the best protection in vivo. Further testing using methyl- and propyl-organophosphates are needed. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article presents a study which compared the importance of oximes and pralidoxime (PRX) for in vitro reactivation of red blood cell acetylcholinesterase inhibited by paraoxon (POX), a non-neuropathic organophosphate. The study found that the new cholinesterase reactivators are superior to PRX, methoxime and B1-6, K-27 oximes. It discovered the importance of in vivo testing in determining the efficacy of new oximes in treating organophosphorus compounds-induced poisoning.

In vitro as well as in vivo evaluation of the reactivating efficacy of various oximes against nerve agent-inhibited acetylcholinesterase has been usually done with the help of animal experiments. Nevertheless, previously published data indicate that the reactivation potency of oximes may be different in human and animal species, which may hamper the extrapolation of animal data to human data. Therefore, to better evaluate the efficacy of various oximes (pralidoxime, obidoxime, HI-6, K033) to reactivate brain acetylcholinesterase inhibited by sarin by in vitro methods, human, rat and pig brain acetylcholinesterase were used to calculate kinetic parameters for the reactivation. Our results show differences among the species, depending on the type of oxime, and indicate that data from animal experiments needs to be carefully evaluated before extrapolation to humans. [ABSTRACT FROM AUTHOR]

Blanka Klimova,1,2 Martin Valis,2 Kamil Kuca3,4 1Department of Applied Linguistics, Faculty of Informatics and Management, University of Hradec Kralove, 2Department of Neurology, 3Biomedical Research Centre, University Hospital Hradec Kralove, 4Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic Abstract: The purpose of this study is to examine the effects of the selected non-pharmacological lifestyle activities on the delay of cognitive decline in normal aging. This was done by conducting a literature review in the four acknowledged databases Web of Science, Scopus, MEDLINE, and Springer, and consequently by evaluating the findings of the relevant studies. The findings show that physical activities, such as walking and aerobic exercises, music therapy, adherence to Mediterranean diet, or solving crosswords, seem to be very promising lifestyle intervention tools. The results indicate that non-pharmacological lifestyle intervention activities should be intense and possibly done simultaneously in order to be effective in the prevention of cognitive decline. In addition, more longitudinal randomized controlled trials are needed in order to discover the most effective types and the duration of these intervention activities in the prevention of cognitive decline, typical of aging population groups. Keywords: cognitive impairment, healthy older individuals, intervention, benefits

Pavel Zonča,1,2 Tomáš Malý,3 Peter Ihnát,1,2 Matus Peteja,1,2 Otakar Kraft,4 Kamil Kuca2,5 1Department of Surgery, University Hospital Ostrava, 2Department of Surgical Studies, Faculty of Medicine, University of Ostrava, Ostrava, 3Department of Surgery, University Hospital Olomouc, Olomouc, 4Department of Nuclear Medicine, University Hospital Ostrava, Ostrava, 5Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic Purpose: The aim of this study was to evaluate the quality of life and functional emptying of J-pouch versus Roux-en-Y reconstruction after total gastrectomy for malignancy. Methods: This study was designed as a prospective, nonblinded, randomized, parallel clinical trial (Trial Number: MN Ostrava, 200604). With informed consent, patients undergoing gastrectomy for malignancy were randomized to J-pouch or Roux-en-Y reconstruction. The time taken for a test semisolid meal labeled with 99mTc-sulfur colloid to exit the reconstructed parts was measured by dynamic scintigraphy 1 year after resection. Quality of life was measured using the Eypasch questionnaire at the same time as functional emptying assessment. This trial was investigator-initiated. Results: In all, 72 patients were included into the study. The time taken for the test meal to exit the postgastrectomy reconstruction was 16.5±10.0 minutes (mean ± standard deviation) in the Roux-en-Y group and 89.4±37.8 minutes in the “J-pouch” group; the difference was statistically significant (P

Petra Marešová,1 Matus Peteja,2 Milan Lerch,2 Pavel Zonca,2 Kamil Kuca3 1Department of Economics, Faculty of Informatics and Management, University of Hradec Kralove, Hradec Kralove, 2Department of Surgical Studies, Faculty of Medicine, University of Ostrava, Ostrava, 3Center of Basic and Applied Research, Faculty of Informatics and Management, University of Hradec Kralove, Hradec Kralove, Czech Republic Objective: Inguinal hernia repair is one of the most frequently carried out operations worldwide. The purpose of this article is to analyze the costs of hernia repair and to specify the loss or profit made under the conditions in the Czech Republic with respect to the currently used medical devices and approaches.Methods: This article is based on the Drummond and O’Brien methodology, which specifically determines the content of direct and indirect costs in health services. The costs of operations during the period 2010–2014 were specified for a total of 746 patients. The cost details are described for four patients who represent the use of different types of medical devices. The procedure was a laparoscopic surgery in all cases.Results: The total costs of inguinal hernia repairs (as per 2015 currency conversion rate) are €1,248,579; only part is covered from public funds, resulting in a loss of €218,359 for the hospital. The obtained data indicate that this operation is unprofitable for hospitals under the present conditions. The loss in the subject facility amounts to 17% of the total cost, which is the cost incurred by the hospital in the Czech Republic.Conclusion: The study conducted in the Czech Republic refers to different economic results when using various medical device types. So the medical device selection depends on advantages or disadvantages for the patients, as well as on the cost effectiveness for the hospital. Keywords: hernia, laparoscopy, cost, medical device, Czech Republic