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22 result(s) for "Sramek, Michal"
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Long-Term Accumulation, Biological Effects and Toxicity of BSA-Coated Gold Nanoparticles in the Mouse Liver, Spleen, and Kidneys
Gold nanoparticles are promising candidates as vehicles for drug delivery systems and could be developed into effective anticancer treatments. However, concerns about their safety need to be identified, addressed, and satisfactorily answered. Although gold nanoparticles are considered biocompatible and nontoxic, most of the toxicology evidence originates from in vitro studies, which may not reflect the responses in complex living organisms. We used an animal model to study the long-term effects of 20 nm spherical AuNPs coated with bovine serum albumin. Mice received a 1 mg/kg single intravenous dose of nanoparticles, and the biodistribution and accumulation, as well as the organ changes caused by the nanoparticles, were characterized in the liver, spleen, and kidneys during 120 days. The amount of nanoparticles in the organs remained high at 120 days compared with day 1, showing a 39% reduction in the liver, a 53% increase in the spleen, and a 150% increase in the kidneys. The biological effects of chronic nanoparticle exposure were associated with early inflammatory and fibrotic responses in the organs and were more pronounced in the kidneys, despite a negligible amount of nanoparticles found in renal tissues. Our data suggest, that although AuNPs belong to the safest nanomaterial platforms nowadays, due to their slow tissue elimination leading to long-term accumulation in the biological systems, they may induce toxic responses in the vital organs, and so understanding of their long-term biological impact is important to consider their potential therapeutic applications.
The Effect of Chemical Structure of OEG Ligand Shells with Quaternary Ammonium Moiety on the Colloidal Stabilization, Cellular Uptake and Photothermal Stability of Gold Nanorods
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). 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. 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 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/cm ) of femtosecond laser irradiation than the alkanethiol MTAB. 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.
Selenium nanoparticles: small innovations with mighty impact on crop performance and nutritional quality?
Selenium (Se), a trace element with dual roles as a micronutrient and toxicant, occupies a unique niche in plant physiology and agricultural science. While not essential for plant growth, selenium’s chemical resemblance to sulfur (S) enables its integration into metabolic pathways. This integration influences redox homeostasis, stress resilience, and the nutritional quality of crops. Recent advancements in nanotechnology have unlocked selenium’s latent potential through the use of engineered selenium nanoparticles (SeNPs), primarily zero-valent elemental (Se 0 ) SeNPs. These nanoparticles mitigate the toxicity risks associated with conventional selenite (Se IV O 3 2− ) or selenate (Se VI O 4 2− ) formulations. SeNPs combine enhanced bioavailability with distinctive physicochemical properties. This combination enables enhanced plant growth, stress tolerance, nutrient uptake, and seed quality. Green synthesis methods using plant extracts offer eco-friendly routes to produce stable, biocompatible SeNPs with controlled size and morphology. In crops, SeNPs modulate metabolic pathways and improve photosynthetic pigments. They also synergize with S compounds to boost yield and nutritional content. Additionally, SeNPs contribute to sustainable agriculture by mitigating biotic and abiotic stresses. They enhance food safety through antimicrobial properties in packaging and animal nutrition. Despite their promise, careful dose management is critical due to the narrow therapeutic window of Se and potential toxicity at higher concentrations. This review explores the latest SeNPs synthesis, selenium’s paradoxical role in plant systems, and its agrobiological impacts. Beyond applications, the review identifies critical methodological gaps in existing research, proposes a characterization set for SeNPs studies, and introduces a comprehensive framework for future research priorities. Graphical abstract
Prognostic significance of early acute kidney injury in COVID-19 patients requiring mechanical ventilation: a single-center retrospective analysis
Acute kidney injury (AKI) is associated with impaired outcomes in critically ill COVID-19 patients. However, the prognostic significance of early AKI is poorly described. We aimed to determine whether AKI on admission to the intensive care unit (ICU) and its development within the first 48 h predict the need for renal replacement therapy (RRT) and increased mortality. An analysis of 372 patients with COVID-19 pneumonia requiring mechanical ventilation without advanced chronic kidney disease from 2020 to 2021 was performed. The AKI stages on ICU admission and Day 2 were determined using adapted KDIGO criteria. The early development of renal function was assessed by the change in AKI score and the Day-2/Day-0 creatinine ratio. Data were compared between three consecutive COVID-19 waves and with data before the pandemic. Both ICU and 90-day mortality (79% and 93% vs. 35% and 44%) and the need for RRT increased markedly with advanced AKI stage on ICU admission. Similarly, an early increase in AKI stage and creatinine implied highly increased mortality. RRT was associated with very high ICU and 90-day mortality (72% and 85%), even surpassing that of patients on ECMO. No difference was found between consecutive COVID-19 waves, except for a lower mortality in the patients on RRT in the last omicron wave. Mortality and need for RRT were comparable in the COVID-19 and pre-COVID-19 patients, except that RRT did not increase ICU mortality in the pre-COVID-19 era. In conclusion, we confirmed the prognostic significance of both AKI on ICU admission and its early development in patients with severe COVID-19 pneumonia.
Ventilatory efficiency is superior to peak oxygen uptake for prediction of lung resection cardiovascular complications
Ventilatory efficiency (V.sub.E /VCO.sub.2 slope) has been shown superior to peak oxygen consumption (VO.sub.2) for prediction of post-operative pulmonary complications in patients undergoing thoracotomy. V.sub.E /VCO.sub.2 slope is determined by ventilatory drive and ventilation/perfusion mismatch whereas VO.sub.2 is related to cardiac output and arteriovenous oxygen difference. We hypothesized pre-operative VO.sub.2 predicts post-operative cardiovascular complications in patients undergoing lung resection. Lung resection candidates from a published study were evaluated by post-hoc analysis. All of the patients underwent preoperative cardiopulmonary exercise testing. Post-operative cardiovascular complications were assessed during the first 30 post-operative days or hospital stay. One-way analysis of variance or the Kruskal-Wallis test, and multivariate logistic regression were used for statistical analysis and data summarized as median (IQR). Of 353 subjects, 30 (9%) developed pulmonary complications only (excluded from further analysis), while 78 subjects (22%) developed cardiovascular complications and were divided into two groups for analysis: cardiovascular only (n = 49) and cardiovascular with pulmonary complications (n = 29). Compared to patients without complications (n = 245), peak VO.sub.2 was significantly lower in the cardiovascular with pulmonary complications group [19.9 ml/kg/min (16.5-25) vs. 16.3 ml/kg/min (15-20.3); P<0.01] but not in the cardiovascular only complications group [19.9 ml/kg/min (16.5-25) vs 19.0 ml/kg/min (16-23.1); P = 0.18]. In contrast, V.sub.E /VCO.sub.2 slope was significantly higher in both cardiovascular only [29 (25-33) vs. 31 (27-37); P = 0.05] and cardiovascular with pulmonary complication groups [29 (25-33) vs. 37 (34-42); P<0.01)]. Logistic regression analysis showed V.sub.E /VCO.sub.2 slope [OR = 1.06; 95%CI (1.01-1.11); P = 0.01; AUC = 0.74], but not peak VO.sub.2 to be independently associated with post-operative cardiovascular complications. V.sub.E /VCO.sub.2 slope is superior to peak VO.sub.2 for prediction of post-operative cardiovascular complications in lung resection candidates.
Impact of COVID-19 isolation measures on ICU microbial resistance dynamics: simulation-based statistical modeling analysis
Background The transmission of antibiotic-resistant bacteria in intensive care units (ICUs) poses a significant challenge to infection control and patient safety. While direct patient-to-patient transmission is well documented, the relative contributions of endogenous bacterial selection and cross-transmission remain uncertain. Methods This retrospective study analyzed microbiological data from two ICUs at St. Anne’s University Hospital in Brno, Czech Republic, between 2018 and 2021. Machine learning algorithms and random simulation models were employed to evaluate clustering patterns of resistant bacterial detections and to distinguish between exogenous cross-transmission and endogenous bacterial acquisition. Bacterial findings were compared across three epidemiologically distinct periods—precovid, covid, and intercovid—characterized by differing hygiene protocols and patient populations. The study assumes that the historically unprecedented hygiene measures during the COVID-19 pandemic substantially reduced horizontal cross-transmission, thereby providing a unique opportunity to estimate the relative contributions of exogenous transmission and endogenous acquisition under routine ICU conditions. Results The prevalence of Pseudomonas aeruginosa (PSAE) was four times higher during the covid period than precovid and remained elevated in the intercovid period. Stenotrophomonas maltophilia detections tripled during covid, while Klebsiella pneumoniae and Escherichia coli resistant to cefotaxime doubled. The proportion of first bacterial detections occurring after 48 h of ICU admission was significantly higher during covid. Clustering analysis revealed no significant deviation from random distribution for most bacteria, except for PSAE, which exhibited non-random clustering, particularly in the intercovid period. Stenotrophomonas maltophilia showed a highly uneven distribution between the two ICUs, suggesting long-term environmental persistence. Conclusion Our findings suggest that antibiotic selection pressure is the primary driver of resistant bacteria acquisition in ICUs, while direct cross-transmission appears to play a limited role. However, environmental persistence may contribute to the recurrent detection of Stenotrophomonas maltophilia , emphasizing the need for enhanced decontamination strategies.
Empagliflozin-associated postoperative mixed metabolic acidosis. Case report and review of pathogenesis
Background Euglycemic diabetic ketoacidosis associated with SGLT2 inhibitors is a rare, relatively new and potentially fatal clinical entity, characterized by metabolic acidosis with normal or only moderately elevated glycemia. The mechanisms are not fully understood but involve increased ketogenesis and complex renal metabolic dysfunction, resulting in both ketoacidosis and hyperchloremic acidosis. We report a rare case of fatal empagliflozin-associated acidosis with profound hyperchloremia and review its pathogenesis. Case presentation A patient with type 2 diabetes mellitus treated with empagliflozin underwent an elective hip replacement surgery. Since day 4 after surgery, he felt generally unwell, leading to cardiac arrest on the day 5. Empagliflozin-associated euglycemic diabetic ketoacidosis with severe hyperchloremic acidosis was identified as the cause of the cardiac arrest. Conclusions This unique case documents the possibility of severe SGLT2 inhibitor-associated mixed metabolic acidosis with a predominant hyperchloremic component. Awareness of this possibility and a high index of suspicion are crucial for correct and early diagnosis.
Rutting Prediction Models in Holistic Concept to Sustainability of Semi-Rigid Pavements
Authors have long been guided by the following premise in their research, educational, professional and publishing activities. Components of the Integrated Transport Infrastructure (ITI) of Slovakia, including roads, should be designed, built, managed, maintained, recycled (decomposed) at a reasonable price, in reasonable quality, respecting the relevant requirements of users, residents and sustainable development throughout life cycle. Elements of ITI Slovakia, as important landscape ecological elements, should be designed with respect to aesthetic principles considering the cultural and natural wealth of Slovakia. Slovak technical universities have recently been criticized for teaching 50-years-old curriculum. The authors dare to disagree with the statement and, due to their scientific profile, pre-sent their partial outputs of a holistic approach to the sustainability of transport structures with a priority focus on pavement. In the intentions of the above mentioned, it could perhaps be partly convergently concluded that they learn new things in the field of transport construction, but under the old names.
Experimental Study of the Volumetric Error Effect on the Resulting Working Accuracy—Roundness
Currently, various types of software compensations are applied to machine tools. Their aim is to increase the working accuracy of the tools. The improvement in working accuracy is then further assessed according to the increase in the dimensional and shape accuracy or the surface quality of the workpiece. This publication describes the effects of the volumetric accuracy of a machine tool on the working accuracy of a workpiece, where total roundness (RONt) is evaluated in multiple cuts. In the experiment, two test workpieces are manufactured on a three-axis milling machining centre. The first is made using a standard machine setup while the second with activated volumetric compensation. The LaserTRACER self-tracking laser interferometer is used to compensate for volumetric accuracy. In the second part, verification measurements are performed with a Ballbar, where roundness error is evaluated according to ISO 230-4. Then two test workpieces are machined, and, in the last part, measurement is performed on Talyrond 595S roundness measuring equipment. Finally, the results are analysed and the dependence between the volumetric accuracy, the circularity error of the machine and the working accuracy of the CNC machine tool is established, represented by the RONt of the workpiece. This paper presents new and unpublished relations between the volumetric accuracy of the machine tool and the RONt of the workpiece.