N-Methyl-d-aspartate receptors (NMDARs) play a crucial role in excitatory neurotransmission, with numerous pathogenic variants identified in the GluN subunits, including their ligand-binding domains (LBDs). The prevailing hypothesis postulates that the endoplasmic reticulum (ER) quality control machinery verifies the agonist occupancy of NMDARs, but this was tested in a limited number of studies. Using microscopy and electrophysiology in the human embryonic kidney 293 (HEK293) cells, we found that surface expression of GluN1/GluN2A receptors containing a set of alanine substitutions within the LBDs correlated with the measured EC50 values for glycine (GluN1 subunit mutations) while not correlating with the measured EC50 values for l-glutamate (GluN2A subunit mutations). The mutant cycle of GluN1-S688 residue, including the pathogenic GluN1-S688Y and GluN1-S688P variants, showed a correlation between relative surface expression of the GluN1/GluN2A receptors and the measured EC50 values for glycine, as well as with the calculated ΔGbinding values for glycine obtained from molecular dynamics simulations. In contrast, the mutant cycle of GluN2A-S511 residue did not show any correlation between the relative surface expression of the GluN1/GluN2A receptors and the measured EC50 values for l-glutamate or calculated ΔGbinding values for l-glutamate. Coexpression of both mutated GluN1 and GluN2A subunits led to additive or synergistic alterations in the surface number of GluN1/GluN2A receptors. The synchronized ER release by ARIAD technology confirmed the altered early trafficking of GluN1/GluN2A receptors containing the mutated LBDs. The microscopical analysis from embryonal rat hippocampal neurons (both sexes) corroborated our conclusions from the HEK293 cells.

• MeSH
• glycin metabolismus   MeSH
• HEK293 buňky MeSH
• hipokampus cytologie   metabolismus   MeSH
• krysa rodu rattus MeSH
• kyselina glutamová metabolismus   MeSH
• lidé MeSH
• ligandy MeSH
• mutace genetika   MeSH
• proteinové domény MeSH
• proteiny nervové tkáně MeSH
• receptory N-methyl-D-aspartátu * metabolismus   genetika   chemie   MeSH
• transport proteinů fyziologie   genetika   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

This study presents a combined experimental and numerical investigation of fiber transport and deposition in a realistic model of the female respiratory tract, extending to the seventh generation of branching. Numerical simulations were performed using the Euler-Lagrange Euler-Rotation (ELER) method, an efficient alternative to conventional Finite Volume Methods that benefits from explicit formulation and vast scalability, enabling fast parallelization on high-performance clusters. The ELER method was coupled with the Lattice Boltzmann Method (LBM) to simulate fiber dynamics under a realistic inspiratory flow profile. Experimental validation was conducted using an identical physical airway replica. The results demonstrated good agreement between simulations and experiments in the upper airways and trachea, with some discrepancies in the bifurcations, likely owing to the challenges of modeling complex turbulent flow with ELER. This method is more accurate than corresponding effective diameter simulations. Deposition patterns were analyzed as a function of fiber dimensions, revealing higher accuracy of the ELER method for smaller particles and confirming the tendency of higher aspect ratio fibers to penetrate deeper into the lungs. The orientation-dependent deposition mechanism was deployed, underscoring the importance of solving the actual orientations of the fibers. While advancing our understanding of fiber transport in female airways, the findings also reveal limitations in current numerical techniques, particularly in bifurcations. This study emphasizes the distinct behavior of fibrous versus spherical particles, with fibers exhibiting a greater propensity to reach deeper lung regions, which has significant implications for inhalation toxicology and drug delivery.

• MeSH
• aplikace inhalační MeSH
• biologické modely * MeSH
• dýchací soustava * MeSH
• lidé MeSH
• plíce MeSH
• počítačová simulace MeSH
• trachea * fyziologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

This paper presents an innovative mathematical model for assessing the dynamics and optimal control of Nipah virus (NiV) with imperfect vaccination. The model formulation considers transmissions through contaminated food and human-to-human contacts. It also incorporates the potential virus transmission through contact with a deceased body infected with NiV. Initially, the NiV model is assessed theoretically, identifying three distinct equilibrium states: the NiV-endemic equilibrium state, the NiV-free equilibrium state, and the equilibrium state involving infected flying foxes. Furthermore, the stability results of the model in the case of constant controls are thoroughly analyzed at the NiV-free equilibrium. Some of the parameters of the model are estimated based on the infected cases documented in Bangladesh from 2001 to 2017. We further perform sensitivity analysis to determine the most influential parameters and formulate effective time-dependent controls. Numerical simulations indicate the optimal course of action for eradicating the disease and provide a comparative analysis of controlling the infection under constant and time-varying interventions. The simulation confirms that the implementation of time-varying interventions is effective in minimizing disease incidence.

• MeSH
• infekce viry z rodu Henipavirus * přenos   prevence a kontrola   epidemiologie   MeSH
• lidé MeSH
• počítačová simulace MeSH
• teoretické modely MeSH
• vakcinace * MeSH
• virus Nipah * imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Bangladéš MeSH

Maximal athletic performance can be limited by various factors, including restricted respiratory function. These limitations can be mitigated through targeted respiratory muscle training, as supported by numerous studies. However, the full potential of respiratory training in competitive finswimming has not been fully investigated. This case study aims to evaluate the effects of eight-week respiratory muscle training (RMT) on performance variability during the underwater phases of a 200 m bi-fins race simulation in an elite finswimmer (current world record holder and multiple world championship medalist). Performance variability was assessed based on pre-test, inter-test, and post-test data. Each measurement included pulmonary function and swim performance evaluations. In this study, underwater performance parameters, such as distance, time, velocity, and number of kicks, were assessed using video analysis synchronized with race timing and evaluated using the Dartfish software. The swimmer followed a 28-day training program with an Airofit PROTM respiratory trainer between tests, with daily sessions targeting both inspiratory and expiratory muscles. The training involved 6-10 min of targeted exercises per day. Significant improvements were observed in Wilcoxon's paired-sample test between the pre-test and post-test results in terms of underwater distance (p = 0.012; d = 1.26), underwater time (p = 0.012; d = 1.26), and number of underwater kicks (p = 0.043; d = 1.01), resulting in a 14.23% longer underwater distance, 14.08% longer underwater time, and 14.94% increase in underwater kicks. Despite the increased distance and time, underwater velocity remained stable, indicating improved underwater performance efficiency. Despite some improvements, it is not possible to conclude that respiratory muscle training (RMT) can contribute to improved finswimming performance during the underwater phases of a 200 m bi-fins race simulation in this particular athlete's case. Further research with a larger sample size is necessary to fully understand the impact of RMT on finswimming performance.

• Publikační typ
• časopisecké články MeSH

INTRODUCTION: This work focuses on the Dengue-viremia ABC (Atangana-Baleanu Caputo) fractional-order differential equations, accounting for both symptomatic and asymptomatic infected cases. Symptomatic cases are characterized by higher viremia levels, whereas asymptomatic cases exhibit lower viremia levels. The fractional-order model highlights memory effects and other advantages over traditional models, offering a more comprehensive representation of dengue dynamics. METHODS: The total population is divided into four compartments: susceptible, asymptomatic infected, symptomatic infected, and recovered. The model incorporates an immune-boosting factor for asymptomatic infected individuals and clinical treatment for symptomatic cases. Positivity and boundedness of the model are validated, and both local and global stability analyses are performed. The novel Adams-Bash numerical scheme is utilized for simulations to rigorously assess the impact of optimal control interventions. RESULTS: The results demonstrate the effectiveness of the proposed control strategies. The reproduction numbers must be reduced based on specific optimal control conditions to effectively mitigate disease outbreaks. Numerical simulations confirm that the optimal control measures can significantly reduce the spread of the disease. DISCUSSION: This research advances the understanding of Dengue-viremia dynamics and provides valuable insights into the application of ABC fractional-order analysis. By incorporating immune-boosting and clinical treatment into the model, the study offers practical guidelines for implementing successful disease control strategies. The findings highlight the potential of using optimal control techniques in public health interventions to manage disease outbreaks more effectively.

• MeSH
• dengue * MeSH
• epidemický výskyt choroby MeSH
• lidé MeSH
• viremie * MeSH
• virus dengue imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Aortic dissection is a life-threatening disease that consists in the development of a tear in the wall of the aorta. The initial tear propagates as a discontinuity leading to separation within the aortic wall, which can result in the creation of a so-called false lumen. A fatal threat occurs if the rupture extends through the whole thickness of the aortic wall, as blood may then leak. It is generally accepted that the dissection, which can sometime extend along the entire length of the aorta, propagates via a delamination mechanism. The aim of the present paper is to provide experimentally validated parameters of a mathematical model for the description of the wall's cohesion. A model of the peeling experiment was built in Abaqus. The delamination interface was described by a piecewise linear traction-separation law. The bulk behavior of the aorta was assumed to be nonlinearly elastic, anisotropic, and incompressible. Our simulations resulted in estimates of the material parameters for the traction-separation law of the human descending thoracic aorta, which were obtained by minimizing the differences between the FEM predictions and the delamination force given by the regression of the peeling experiments. The results show that the stress at damage initiation, Tc, should be understood as an age-dependent quantity, and under the assumptions of our model this dependence can be expressed by linear regression as Tc = - 13.03·10-4·Age + 0.2485 if the crack front advances in the axial direction, and Tc = - 7.58·10-4·Age + 0.1897 if the crack front advances in the direction of the aortic circumference (Tc [MPa], Age [years]). Other model parameters were the stiffness K and the separation at failure, δf-δc (K = 0.5 MPa/mm, δf-δc = 0.1 mm). The material parameters provided by our study can be used in numerical simulations of the biomechanics of dissection propagation through the aorta especially when age-associated phenomena are studied.

• MeSH
• analýza metodou konečných prvků MeSH
• aorta thoracica * fyziologie   MeSH
• biomechanika MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mechanický stres MeSH
• modely kardiovaskulární MeSH
• počítačová simulace MeSH
• senioři MeSH
• stárnutí fyziologie   MeSH
• trakce MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

The single-stranded RNA genome of SARS-CoV-2 is highly structured. Numerous helical stem-loop structures interrupted by mismatch motifs are present in the functionally important 5'- and 3'-UTRs. These mismatches modulate local helical geometries and feature unusual arrays of hydrogen bonding donor and acceptor groups. However, their conformational and dynamical properties cannot be directly inferred from chemical probing and are difficult to predict theoretically. A mismatch motif (SL1-motif) consisting of three consecutive U•U base pairs is located in stem-loop 1 of the 3'-UTR. We combined NMR-spectroscopy and MD-simulations to investigate its structure and dynamics. All three U•U base pairs feature two direct hydrogen bonds and are as stable as Watson-Crick A:U base pairs. Plasmodium falciparum 25S rRNA contains a triple U•U mismatch motif (Pf-motif) differing from SL1-motif only with respect to the orientation of the two closing base pairs. Interestingly, while the geometry of the outer two U•U mismatches was identical in both motifs the preferred orientation of the central U•U mismatch was different. MD simulations and potassium ion titrations revealed that the potassium ion-binding mode to the major groove is connected to the different preferred geometries of the central base pair in the two motifs.

• MeSH
• 3' nepřekládaná oblast * MeSH
• chybné párování bází * MeSH
• COVID-19 virologie   MeSH
• genom virový MeSH
• konformace nukleové kyseliny MeSH
• lidé MeSH
• nukleotidové motivy * MeSH
• párování bází MeSH
• Plasmodium falciparum genetika   MeSH
• RNA virová * chemie   genetika   MeSH
• SARS-CoV-2 * genetika   chemie   MeSH
• simulace molekulární dynamiky MeSH
• vodíková vazba MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Telemedicine is an emerging development in the healthcare domain, where the Internet of Things (IoT) fiber optics technology assists telemedicine applications to improve overall digital healthcare performances for society. Telemedicine applications are bowel disease monitoring based on fiber optics laser endoscopy, gastrointestinal disease fiber optics lights, remote doctor-patient communication, and remote surgeries. However, many existing systems are not effective and their approaches based on deep reinforcement learning have not obtained optimal results. This paper presents the fiber optics IoT healthcare system based on deep reinforcement learning combinatorial constraint scheduling for hybrid telemedicine applications. In the proposed system, we propose the adaptive security deep q-learning network (ASDQN) algorithm methodology to execute all telemedicine applications under their given quality of services (deadline, latency, security, and resources) constraints. For the problem solution, we have exploited different fiber optics endoscopy datasets with images, video, and numeric data for telemedicine applications. The objective is to minimize the overall latency of telemedicine applications (e.g., local, communication, and edge nodes) and maximize the overall rewards during offloading and scheduling on different nodes. The simulation results show that ASDQN outperforms all telemedicine applications with their QoS and objectives compared to existing state action reward state (SARSA) and deep q-learning network (DQN) policy during execution and scheduling on different nodes.

• MeSH
• algoritmy MeSH
• deep learning * MeSH
• internet věcí * MeSH
• lidé MeSH
• technologie optických vláken MeSH
• telemedicína * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Understanding the risk factors leading to intracranial aneurysm (IA) rupture have still not been fully clarified. They are vital for proper medical guidance of patients harboring unruptured IAs. Clarifying the hemodynamics associated with the point of rupture could help could provide useful information about some of the risk factors. Thus far, few studies have studied this issue with often diverging conclusions. METHODS: We identified a point of rupture in patients operated for an IAs during surgery, using a combination of preoperative computed tomography (CT) and computed tomography angiography (CTA). Hemodynamic parameters were calculated both for the aneurysm sac as a whole and the point of rupture. In two cases, the results of CFD were compared with those of the experiment using particle image velocimetry (PIV). RESULTS: We were able to identify 6 aneurysms with a well-demarcated point of rupture. In four aneurysms, the rupture point was near the vortex with low wall shear stress (WSS) and high oscillatory shear index (OSI). In one case, the rupture point was in the flow jet with high WSS. In the last case, the rupture point was in the significant bleb and no specific hemodynamic parameters were found. The CFD results were verified in the PIV part of the study. CONCLUSION: Our study shows that different hemodynamic scenarios are associated with the site of IA rupture. The numerical simulations were confirmed by laboratory models. This study further supports the hypothesis that various pathological pathways may lead to aneurysm wall damage resulting in its rupture.

• Publikační typ
• časopisecké články MeSH

A mathematical model of myocardial perfusion based on the lattice Boltzmann method (LBM) is proposed and its applicability is investigated in both healthy and diseased cases. The myocardium is conceptualized as a porous material in which the transport and mass transfer of a contrast agent in blood flow is studied. The results of myocardial perfusion obtained using LBM in 1D and 2D are confronted with previously reported results in the literature and the results obtained using the mixed-hybrid finite element method. Since LBM is not suitable for simulating flow in heterogeneous porous media, a simplified and computationally efficient 1D-analog approach to 2D diseased case is proposed and its applicability discussed.

• MeSH
• analýza metodou konečných prvků * MeSH
• kontrastní látky MeSH
• koronární cirkulace fyziologie   MeSH
• lidé MeSH
• modely kardiovaskulární * MeSH
• počítačová simulace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH