Herbal medications have an extensive history of use in treating various diseases, attributed to their perceived efficacy and safety. Traditional medicine practitioners and contemporary healthcare providers have shown particular interest in herbal syrups, especially for respiratory illnesses associated with the SARS-CoV-2 virus. However, the current understanding of the pharmacokinetic and toxicological properties of phytochemicals in these herbal mixtures is limited. This study presents a comprehensive computational analysis utilizing novel approach methodologies (NAMs) to investigate the pharmacokinetic and toxicological profiles of phytochemicals in herbal syrup, leveraging in-silico techniques and prediction tools such as PubChem, SwissADME, and Molsoft's database. Although molecular dynamics, docking, and broader system-wide analyses were not considered, future studies hold potential for further investigation in these areas. By combining drug-likeness with molecular simulation, researchers identify diverse phytochemicals suitable for complex medication development examining their pharmacokinetic-toxicological profiles in phytopharmaceutical syrup. The study focuses on herbal solutions for respiratory infections, with the goal of adding to the pool of all-natural treatments for such ailments. This research has the potential to revolutionize environmental and alternative medicine by leveraging in-silico models and innovative analytical techniques to identify novel phytochemicals with enhanced therapeutic benefits and explore network-based and systems biology approaches for a deeper understanding of their interactions with biological systems. Overall, our study offers valuable insights into the computational analysis of the pharmacokinetic and toxicological profiles of herbal concoction. This paves the way for advancements in environmental and alternative medicine. However, we acknowledge the need for future studies to address the aforementioned topics that were not adequately covered in this research.

• Publikační typ
• časopisecké články MeSH

Carcinogenic chemicals, or their metabolites, can be classified as genotoxic or non-genotoxic carcinogens (NGTxCs). Genotoxic compounds induce DNA damage, which can be detected by an established in vitro and in vivo battery of genotoxicity assays. For NGTxCs, DNA is not the primary target, and the possible modes of action (MoA) of NGTxCs are much more diverse than those of genotoxic compounds, and there is no specific in vitro assay for detecting NGTxCs. Therefore, the evaluation of the carcinogenic potential is still dependent on long-term studies in rodents. This 2-year bioassay, mainly applied for testing agrochemicals and pharmaceuticals, is time-consuming, costly and requires very high numbers of animals. More importantly, its relevance for human risk assessment is questionable due to the limited predictivity for human cancer risk, especially with regard to NGTxCs. Thus, there is an urgent need for a transition to new approach methodologies (NAMs), integrating human-relevant in vitro assays and in silico tools that better exploit the current knowledge of the multiple processes involved in carcinogenesis into a modern safety assessment toolbox. Here, we describe an integrative project that aims to use a variety of novel approaches to detect the carcinogenic potential of NGTxCs based on different mechanisms and pathways involved in carcinogenesis. The aim of this project is to contribute suitable assays for the safety assessment toolbox for an efficient and improved, internationally recognized hazard assessment of NGTxCs, and ultimately to contribute to reliable mechanism-based next-generation risk assessment for chemical carcinogens.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Data mining (DM) is a widely adopted methodology for the analysis of large datasets which is on the other hand often overestimated or incorrectly considered as a universal solution. This statement is also valid for clinical research, in which large and heterogeneous datasets are often processed. DM in general uses standard methods available in common statistical software and combines them into a complex workflow methodology covering all the steps of data analysis from data acquisition through pre-processing and data analysis to interpretation of the results. The whole workflow is aimed at one final goal – to find any interesting, non-trivially hidden and potentially useful information. This innovative concept of data mining was adopted in our educational course of the Faculty of Medicine at the Masaryk University accessible from its e-learning portal http://portal. med.muni.cz/clanek-318-zavedeni-technologie-data-miningu-a-analyzy-dat--genovych-expresnich-map-do-vyuky.html.

• MeSH
• biostatistika metody   MeSH
• data mining * metody   trendy   MeSH
• lidé MeSH
• multifaktorová rozměrová redukce metody   MeSH
• počítačem řízená výuka * metody   trendy   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

BACKGROUND: Out of 185 orphan medicinal products (OMPs) registered in 2015-2021, a mere 110 (59 percent) were available to Czech patients, and only 54 (29 percent) were officially reimbursed. Moreover, this proportion has steadily decreased over time. After years of public debate induced by this unsatisfactory OMP patient access, the national viewpoint shifted toward creating a special pathway for the reimbursement of OMP. Thus, a rigorous pricing and reimbursement procedure with strict timelines and elaborated methodology has been recently adopted in Czechia. METHODOLOGY: The innovative legislation follows the recommendations for value assessment and funding processes for rare diseases and incorporates additional elements of value, such as the societal perspective. First, the application with clinical evidence, cost-effectiveness, and budget impact analyses is submitted to the governmental health technology assessment (HTA) agency by the Marketing Authorization Holder or a Health Insurance Fund. Moreover, professional associations and patients' organizations are rightful participants in the proceeding, providing evidence and comments. Then, the HTA agency performs the assessment/appraisal of the evidence. It subsequently publishes the assessment report summarizing available information. The report is then forwarded to the Ministry of Health and its advisory body consisting of patients, clinical experts, health insurance funds, and the State. They critically evaluate the documents and issue a binding opinion following prespecified decision-making criteria. Based on this binding opinion, the decision is issued by the HTA agency. Thus, the role of the advisory body in this process is crucial. CONCLUSION: We believe that this novel approach may offer satisfactory patient access to orphan drugs. Moreover, it serves as a real-world example of "value-based" decision making.

• MeSH
• hodnocení biomedicínských technologií MeSH
• lidé MeSH
• rozhodování MeSH
• úhrada zdravotního pojištění MeSH
• výroba orphan drugs * MeSH
• vzácné nemoci * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: Hosts repeatedly bitten by sand flies develop antibodies against sand fly saliva and screening of these immunoglobulins can be employed to estimate the risk of Leishmania transmission, to indicate the feeding preferences of sand flies, or to evaluate the effectiveness of vector control campaigns. Previously, antibodies to sand fly saliva were detected using whole salivary gland homogenate (SGH) or recombinant proteins, both of which also have their disadvantages. This is the first study on sand flies where short peptides designed based on salivary antigens were successfully utilized for antibody screening. METHODOLOGY/PRINCIPAL FINDINGS: Specific IgG was studied in hosts naturally exposed to Phlebotomus orientalis, the main vector of Leishmania donovani in East Africa. Four peptides were designed by the commercial program EpiQuest-B, based on the sequences of the two most promising salivary antigens, yellow-related protein and ParSP25-like protein. Short amino acid peptides were synthesised and modified for ELISA experiments. Specific anti-P. orientalis IgG was detected in sera of dogs, goats, and sheep from Ethiopia. The peptide OR24 P2 was shown to be suitable for antibody screening; it correlated positively with SGH and its specificity and sensitivity were comparable or even better than that of previously published recombinant proteins. CONCLUSIONS/SIGNIFICANCE: OR24 P2, the peptide based on salivary antigen of P. orientalis, was shown to be a valuable tool for antibody screening of domestic animals naturally exposed to P. orientalis. We suggest the application of this promising methodology using species-specific short peptides to other sand fly-host combinations.

• MeSH
• ELISA metody   MeSH
• imunoglobulin G krev   MeSH
• kozy MeSH
• ovce MeSH
• peptidy imunologie   MeSH
• Phlebotomus imunologie   MeSH
• plošný screening metody   MeSH
• protilátky krev   MeSH
• psi MeSH
• senzitivita a specificita MeSH
• slinné proteiny a peptidy imunologie   MeSH
• zvířata MeSH
• Check Tag
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Etiopie MeSH

AIMS: Glycaemic variability (GV) has been hypothesized to increase the risk of diabetes complications; however, results of clinical studies are contradictory. The effect of GV on cell phenotypes has been investigated in vitro showing that GV may have more deleterious effect on cells that high glucose itself. However, methodology used to study GV in vitro differs significantly between studies and does not reflect in vivo situation. Therefore we aimed to establish clinically relevant an in vitro experimental approach for the study of GV that reflects intra-day glucose fluctuations of subjects with type 1 diabetes mellitus (T1DM) and of healthy subjects and to test how low and high GV affect expression of genes that protects cells from hyperglycaemia-induced damage. METHODS: Human umbilical vein endothelial cells (HUVEC) were cultured 24h in medium with different glucose profiles: high GV, low GV and GV of healthy subjects-profiles created according to CGM of T1DM patients and healthy subjects. These profiles were compared to commonly used 5.5 and 25mmol/l glucose concentrations. Gene expression was determined using quantitative PCR. RESULTS: Our results showed general down-regulation of enzymes that are involved in the protection against hyperglycaemia-induced intracellular changes in both low and high GV compared to normal glycaemia similarly to the decrease induced by continuous hyperglycaemia. Gene expressions did not differ between high and low GV. CONCLUSION: Our data indicate that GV may have similar or even greater effect than continuous hyperglycaemia on the expression of several genes relevant to pathogenesis of diabetes microvascular complications.

• MeSH
• apoptóza účinky léků   MeSH
• biologické markery metabolismus   MeSH
• diabetes mellitus 1. typu komplikace   farmakoterapie   patofyziologie   MeSH
• endoteliální buňky pupečníkové žíly (lidské) účinky léků   metabolismus   MeSH
• glukosa škodlivé účinky   MeSH
• hyperglykemie etiologie   patologie   MeSH
• hypoglykemie etiologie   patologie   MeSH
• krevní glukóza metabolismus   MeSH
• kultivované buňky MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé MeSH
• messenger RNA genetika   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• proliferace buněk účinky léků   MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• stanovení celkové genové exprese MeSH
• studie případů a kontrol MeSH
• techniky in vitro MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

OBJECTIVES: Propose a methodology to identify COVID-19 associated deaths using healthcare billing records and evaluate its effectiveness by comparing the results with excess mortality data from 2020 to 2022 and confirmed COVID-19 deaths. METHODS: A retrospective quantitative analysis was conducted by merging healthcare billing records with cause of death data. The term "COVID-19 associated death" was defined as any death occurring within a defined timeframe following a confirmed contact with COVID-19. This category includes individuals who died directly due to COVID-19, with COVID-19 as a contributing factor, or as an aftermath of a COVID-19 infection, as well as those who died from other causes but had previously contracted COVID-19. This broader definition provides a more comprehensive measure of excess mortality compared to the officially confirmed COVID-19 deaths attributed to the virus. RESULTS: We identified 35,399 COVID-19 associated deaths during the 3-year pandemic in Slovakia compared to 21,395 confirmed COVID-19 deaths. CONCLUSION: The identification of COVID-19 associated deaths with our methodology offers a more accurate explanation for the notably high excess mortality observed in Slovakia (31,789 deaths) during the pandemic, relative to the EU27. Given the high level of excess mortality, the officially confirmed deaths are likely underestimated, and the presented methodology provides a more precise measure of mortality. Additionally, healthcare billing records prove valuable in identifying these deaths at the individual patient level using claims data of health insurance companies, which is crucial for implementing targeted preventive measures and improving preparedness for future pandemics.

• MeSH
• COVID-19 * mortalita   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• pandemie MeSH
• příčina smrti * MeSH
• retrospektivní studie MeSH
• SARS-CoV-2 MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Slovenská republika MeSH

AIM: The aim of this study was to evaluate adherence to spironolactone in a group of unselected patients with arterial hypertension by analysis of measured serum spironolactone and canrenone concentrations according to a proposed two-step decision scheme based on pharmacokinetic considerations. MATERIALS AND METHODS: Simulation of serum concentration-time profiles of spironolactone and canrenone based on population pharmacokinetic parameters described in literature and a body weight-normalized spironolactone dose / canrenone level nomogram derived from a group of adherent patients with conservatively treated primary hyperaldosteronism, were used to create a two-step decision scheme. 71 outpatients treated with spironolactone for resistant hypertension with spironolactone and canrenone serum concentrations measured between 2018 and 2021 were analyzed according to the proposed scheme. We compared our proposed methodology to the standard approach for adherence testing. RESULTS: With the most sensitive traditional approach to adherence assessment through detectable serum concentrations of spironolactone and/or canrenone, 9 (12.7%) non-adherent patients were identified. With our two-step assessment of adherence, we were able to identify 18 (25.4%) non-adherent patients. CONCLUSION: Consideration of the pharmacokinetic properties of parental drug and its metabolite led to improved sensitivity in non-adherence detection in patients with arterial hypertension. This approach enables better interpretation of measured spironolactone and canrenone serum concentrations and should be used in clinical practice.

• MeSH
• adherence k farmakoterapii * MeSH
• antagonisté mineralokortikoidních receptorů farmakokinetika   MeSH
• dospělí MeSH
• hyperaldosteronismus farmakoterapie   krev   MeSH
• hypertenze * farmakoterapie   MeSH
• kanrenon * farmakokinetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pilotní projekty MeSH
• senioři MeSH
• spironolakton * farmakokinetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

For ethical reasons and animal welfare, it is becoming increasingly more important to carry out ecological surveys with a non-invasive approach. Information about fish distribution and abundance in the upper water column is often fundamental. However, this information is extremely hard to obtain using classical hydroacoustic methods. We developed a rigid frame system for pushing upward looking transducers of the scientific echo sounder (38 and 120 kHz) in front of the research vessel. The efficiency of the new approach for monitoring juvenile fish at night was investigated by comparing the results with a quantitative fry trawl in the Římov Reservoir in the Czech Republic. The experimental setup enabled comparisons for the 0-3 m and 3-6 m depth layers, which are utilized by almost all juvenile fish in summer. No statistically significant differences in the estimated abundance of juveniles were found between the two sampling methods. The comparison of abundance estimates gathered by the two frequencies were also not significantly different. The predicted mean lengths from acoustic sampling and the trawl catches differed by less than 10 mm in all comparisons. Results suggest that mobile hydroacoustic upward-looking systems can fill the methodological gap in non-invasive surveying of surface fishes.

• MeSH
• akustika přístrojové vybavení   MeSH
• jezera MeSH
• měniče MeSH
• populační dynamika MeSH
• průzkumy a dotazníky MeSH
• roční období MeSH
• rozšíření zvířat fyziologie   MeSH
• rybářství statistika a číselné údaje   MeSH
• ryby fyziologie   MeSH
• zachování přírodních zdrojů * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Assessment of retinal blood flow inside the optic nerve head (ONH) and the peripapillary area is an important task in retinal imaging. For this purpose, an experimental binocular video ophthalmoscope that acquires precisely synchronized video sequences of the optic nerve head and peripapillary area from both eyes has been previously developed. It enables to compare specific characteristics of both eyes and efficiently detect the eye asymmetry. In this paper, we describe a novel methodology for the analysis of acquired video data using a photoplethysmographic approach. We describe and calculate the pulsatile attenuation amplitude (PAA) spatial map, which quantifies the maximum relative change of blood volume during a cardiac cycle using a frequency domain approach. We also describe in detail the origin of PAA maps from the fundamental (the first) and the second harmonic component of the pulsatile signal, and we compare the results obtained by time-based and frequency-based approaches. In several cases, we show the advantages and possibilities of this device and the appropriate image analysis approach - fast measurement and comparison of blood flow characteristics of both eyes at a glance, the robustness of this approach, and the possibility of easy detection of asymmetry.

• Publikační typ
• časopisecké články MeSH