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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

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

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

Hana Tomaskova,1 Jitka Kuhnova,2 Richard Cimler,1,3 Ondrej Dolezal,1 Kamil Kuca3 1Faculty of Informatics and Management, 2Faculty of Science, 3Center for Basic and Applied Research (CZAV), University of Hradec Králové, Hradec Králové, Czech Republic Introduction: Alzheimer’s disease (AD) is a slowly progressing neurodegenerative brain disease with irreversible brain effects; it is the most common cause of dementia. With increasing age, the probability of suffering from AD increases. In this research, population growth of the European Union (EU) until the year 2080 and the number of patients with AD are modeled.Aim: The aim of this research is to predict the spread of AD in the EU population until year 2080 using a computer simulation.Methods: For the simulation of the EU population and the occurrence of AD in this population, a system dynamics modeling approach has been used. System dynamics is a useful and effective method for the investigation of complex social systems. Over the past decades, its applicability has been demonstrated in a wide variety of applications. In this research, this method has been used to investigate the growth of the EU population and predict the number of patients with AD. The model has been calibrated on the population prediction data created by Eurostat.Results: Based on data from Eurostat, the EU population until year 2080 has been modeled. In 2013, the population of the EU was 508 million and the number of patients with AD was 7.5 million. Based on the prediction, in 2040, the population of the EU will be 524 million and the number of patients with AD will be 13.1 million. By the year 2080, the EU population will be 520 million and the number of patients with AD will be 13.7 million.Conclusion: System dynamics modeling approach has been used for the prediction of the number of patients with AD in the EU population till the year 2080. These results can be used to determine the economic burden of the treatment of these patients. With different input data, the simulation can be used also for the different regions as well as for different noncontagious disease predictions. Keywords: Alzheimer’s disease, population modeling, system dynamics, prediction model

Blanka Klimova,1 Petra Maresova,2 Kamil Kuca3,4 1Department of Applied Linguistics, 2Department of Economics, Faculty of Informatics and Management, University of Hradec Kralove, 3Biomedical Research Centre, University Hospital Hradec Kralove, 4Center for Basic and Applied Research, Faculty of Informatics and Management, University of Hradec Kralove, Hradec Kralove, Czech Republic Abstract: At present, the number of elderly people is rapidly increasing, which represents a significant threat in terms of their care when they fall ill. One of the most common aging diseases nowadays is dementia, whose symptoms sooner or later include loss of cognitive functioning. Cognitive disorders can vary from serious mental retardation to inability to recall things, to the loss or disorder of specific cognitive functions such as communication. These disorders not only affect the quality of people’s own life but also impose a substantial burden on their families, particularly on their caregivers. Therefore, the aim of this article is to highlight the role of assistive technologies (ATs) for managing language impairments in dementia in order to improve patients’ quality of life. In addition, ATs focused on training patients’ memory are also mentioned, since they can help patients to maintain their language skills. Furthermore, these ATs can delay the need for institutional care, as well as significantly reduce costs on patient care. The importance of future research in the area of the development of ATs for managing the language impairments in dementia is also discussed. There is a general trend toward the personalization of patient needs and requirements in the area of ATs. For the purpose of this article, a method of literature review of available sources defining language disorders and providing characteristic features of language disorders in dementia is used. In addition, a method of comparison of different research studies exploring ATs focused on delaying language disorders in dementia in order to postpone patients’ need for institutional care is also exploited. Keywords: assistive technologies, dementia, language impairments, improvement

Petra Maresova,1 Marek Penhaker,1,2 Ali Selamat,1,3 Kamil Kuca1,41Faculty of Informatics and Management, University of Hradec Králové, Hradec Králové, Czech Republic; 2Department of Cybernetics and Biomedical Engineering, Faculty of Electrical Engineering and Computer Science, Technical University of Ostrava, Poruba, Czech Republic; 3Faculty of Computing, Universiti Teknologi Malaysia, Johor Bahru, Johor, Malaysia; 4Center for Biomedical Research, University Hospital Hradec Králové, Hradec Králové, Czech RepublicAbstract: The high quality of public health improves not only healthy life expectancy, but also the productivity of labor. The most important part of the health care sector is the medical technology industry. The aim of this study is to analyze the current situation in the medical device industry in Europe, its potential strengths and weaknesses in the context of topical economic and demographic development. The contribution specifies an analysis of the economic state of the medical device industry in the context of demographic development of European Union’s macroeconomic indicators and views of experts in the field of medical device development, concerning the opportunities for entities involved in the medical device market. There is fierce competition on the European market. The innovative activity is stable and well regulated by responsible authorities. Worldwide, the medical device market is expected to grow.Keywords: technology context, medical device, Europe, expenditure, review

Hana Mohelska,1 Petra Maresova,2 Martin Valis,3 Kamil Kuca4,5 1Department of Management, 2Department of Economy, Faculty of Informatics and Management, University of Hradec Králové, 3Department of Neurology, Charles University in Prague, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, 4Biomedical Research Centrum, University Hospital Hradec Králové, 5Center for Basic and Applied Research, Faculty of Informatics and Management, University of Hradec Králové, Hradec Králové, Czech Republic Abstract: This paper deals with the analysis of the costs, applied, for example, when treating specific diseases – an important aid in prioritizing the process of resource allocation. In our review, the specific disease is dementia caused by Alzheimer’s disease. This paper aims to provide more information on the partial costs per patient that are calculated according to the aggregated data from publicly available sources as well as from the results of authors’ own investigation. The University Hospital in Hradec Králové and the General Health Insurance Company of the Czech Republic participated in this research. The elementary research objective was to compare the costs per patient diagnosed early onset, to those of the patient diagnosed later. The Czech Republic lacks information regarding dementia. Therefore, these issues require attention. The methods used in this paper included time series analyses, methods of direct questioning, interviews with experts, and analyses of medical documentation. These methods were combined to exploit their particular advantages and to ensure the issues discussed, were covered. The investigation showed that the underpinning of patients with Alzheimer’s disease at early onset is advantageous from an economic perspective, because the cost of outpatient care is much lower compared with that of inpatient care. The international comparisons of the volume of care provided should be approached with great caution. These are based solely on the facts of various expert estimates and are not usually supported by hard data. Yet, they still illustrate the overall view of our ability to take care of people with dementia. According to experts, care in the Czech Republic significantly lags behind the rest of developed Europe. While services are provided to 26% of people with dementia in Germany and 50% in France, the experts estimate that services are provided to only 10% of the population in the Czech Republic. If we were to offer a similar volume of services in the Czech Republic, to the same extent as the average in Europe, we would have to triple the existing capacities. Keywords: mental health expenditure, Czech Republic, dementia, costs, Alzheimer’s disease

Blanka Klimova,1 Petra Maresova,2 Martin Valis,3 Jakub Hort,4,5 Kamil Kuca6,71Department of Applied Linguistics, 2Department of Economics, Faculty of Informatics and Management, University of Hradec Kralove, 3Department of Neurology, Faculty of Medicine in Hradec Kralove and University Hospital Hradec Kralove, Charles University in Prague, Hradec Kralove, 4Department of Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, 5International Clinical Research Center, St Anne’s University Hospital Brno, Brno, 6Center for Basic and Applied Research, Faculty of Informatics and Management, University of Hradec Kralove, 7Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech RepublicAbstract: Communication is very important for people to be successfully integrated into social environment and make and maintain relationship. Particularly, language difficulties lead to social exclusion of the people affected with Alzheimer’s disease (AD) and contribute to a significant decrease in the quality of their life and also have a big impact on their family members who in most cases become their caregivers who need to communicate with their loved ones in order to meet their needs. Therefore, the goal of this study is to describe language impairments in the individual phases of AD and discuss their improvement with respect to AD on the basis of literature review. The authors of this article use traditional research methods in order to achieve the goal set mentioned earlier. First, a method of literature review of available sources describing language impairments in the individual phases of AD is exploited. Second, to show how informal caregivers and relevant drugs can successfully intervene in the improvement of these language impairments, a method of comparison of different research studies exploring such social intervention and medical treatment is used.Keywords: Alzheimer’s disease, language impairments, social intervention, strategies, caregivers, clinical drugs

Jirí Masopust,1,2 Ctirad Andrýs,3 Jan Bažant,1 Oldrich Vyšata,4 Kamil Kuca,5 Martin Vališ4 1Department of Psychiatry, Faculty of Medicine in Hradec Kralové, Charles University in Prague, University Hospital Hradec Králové, Hradec Králové, Czech Republic; 2National Institute of Mental Health, Klecany, Czech Republic; 3Institute of Clinical Immunology and Allergology, Charles University in Prague, Faculty of Medicine in Hradec Králové, and University Hospital Hradec Králové, Hradec Králové, Czech Republic; 4Department of Neurology, Charles University in Prague, Faculty of Medicine in Hradec Králové, and University Hospital Hradec Králové, Hradec Králové, Czech Republic; 5Biomedical Research Centrum, University Hospital Hradec Králové, Hradec Králové, Czech Republic Background: Encephalitis with antibodies against N-methyl-D-aspartate receptor (NMDA-R) is classified as an autoimmune disorder with psychotic symptoms, which are frequently dominant. However, it remains unclear how frequently NMDA-R antibodies lead to a condition that mimics psychosis and first-episode schizophrenia. In our work, we investigated the presence of antibodies against NMDA-R in patients with first-episode psychosis (FEP) in comparison with healthy volunteers.Methods: This study included 50 antipsychotic-naïve patients with FEP (including 21 women) and 50 healthy volunteers (including 21 women). The mean age of the patients was 27.4 (±7.4) years and that of the healthy controls was 27.0 (±7.3) years. Antibodies against NMDA-R in the serum were detected by immunofluorescence.Results: None of the investigated patients with an FEP and none of the healthy controls showed positive antibodies against NMDA-Rs.Conclusion: According to results of studies, a small proportion of patients with an FEP possess antibodies against NMDA-R. However, the extent to which this finding contributes to the etiopathogenesis of the response to antipsychotic medication and whether immunomodulatory therapy is indicated in these cases remains uncertain. Keywords: N-methyl-D-aspartate receptor, NMDA-R, encephalitis, schizophrenia

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