Urine test strips for urinalysis are a common diagnostic tool with minimal costs and are used in various situations including homecare and hospitalization. The coloration scaled by the naked eye is simple, but it is suitable for semiquantitative analysis only. In this paper, a colorimetric assay is developed based on a smartphone digital camera and urine test strips. Assays of pH, albumin, glucose, and lipase activity were performed as a tool for the diagnosis of aciduria, alkaluria, glycosuria, proteinuria, and leukocyturia. The RGB color channels were analyzed in the colorimetric assay, and the assay exerted good sensitivity, and all the particular diagnoses proved to be reliable. The limits of detection for glucose (0.11 mmol/L), albumin (0.15 g/L), and lipase (2.50 U/μL) were low enough to cover the expected physiological concentration, and the range for pH was also satisfactory. The urine test strips with a camera as an output detector proved applicability to spiked urine samples, and the results were also well in comparison to the standard assays which confirms the practical relevance of the presented findings.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Ewing sarcoma (EwS) is a rare and highly malignant bone tumor primarily affecting children, adolescents, and young adults. The pelvis, trunk, and lower extremities are the most common sites, while EwS of the sacrum as a primary site is very rare, and only few studies focusing on this location are published. Due to the anatomical condition, local treatment is challenging in sacral malignancies. We analyzed factors that might influence the outcome of patients suffering from sacral EwS. METHODS: We retrospectively analyzed data of the GPOH EURO-E.W.I.N.G 99 trial and the EWING 2008 trial, with a cohort of 124 patients with localized or metastatic sacral EwS. The study endpoints were overall survival (OS) and event-free survival (EFS). OS and EFS were calculated using the Kaplan-Meier method, and univariate comparisons were estimated using the log-rank test. Hazard ratios (HRs) with respective 95% confidence intervals (CIs) were estimated in a multivariable Cox regression model. RESULTS: The presence of metastases (3y-EFS: 0.33 vs. 0.68; P < 0.001; HR = 3.4, 95% CI 1.7 to 6.6; 3y-OS: 0.48 vs. 0.85; P < 0.001; HR = 4.23, 95% CI 1.8 to 9.7), large tumor volume (≥200 ml) (3y-EFS: 0.36 vs. 0.69; P=0.02; HR = 2.1, 95% CI 1.1 to 4.0; 3y-OS: 0.42 vs. 0.73; P=0.04; HR = 2.1, 95% CI 1.03 to 4.5), and age ≥18 years (3y-EFS: 0.41 vs. 0.60; P=0.02; HR = 2.6, 95% CI 1.3 to 5.2; 3y-OS: 0.294 vs. 0.59; P=0.01; HR = 2.92, 95% CI 1.29 to 6.6) were revealed as adverse prognostic factors. CONCLUSION: Young age seems to positively influence patients` survival, especially in patients with primary metastatic disease. In this context, our results support other studies, stating that older age has a negative impact on survival. Tumor volume, metastases, and the type of local therapy modality have an impact on the outcome of sacral EwS. Level of evidence: Level 2. This trial is registered with NCT00020566 and NCT00987636.
- Publikační typ
- časopisecké články MeSH
Point-of-care ultrasound examinations performed by physicians of different specialties are a rapidly growing phenomenon, which has led to a worldwide effort to create a standardised approach to ultrasound examination training. The implementation of emergency echocardiography by noncardiologists is mainly aimed at the standardisation of the procedure, a structured training system, and an agreement on competencies. This article summarises the current training programmes for nonechocardiographers at the University Hospital in Hradec Králové. In cooperation with cardiologists specialised in cardiac ultrasound (ECHO), an extended acute echo protocol dedicated to emergency department physicians was developed and validated in daily practice. According to our retrospective evaluation, after one year of clinical practice, we can confirm that point-of-care ultrasound examinations performed using the standardised limited echo protocol are safe and accurate. The observed concordance with comprehensive ECHO was 78%. This trial is registered with NCT05306730.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Cancer management faces multiple obstacles, including resistance to current therapeutic approaches. In the face of challenging microenvironments, cancer cells adapt metabolically to maintain their supply of energy and precursor molecules for biosynthesis and thus sustain rapid proliferation and tumor growth. Among the various metabolic adaptations observed in cancer cells, the altered glucose metabolism is the most widely studied. The aberrant glycolytic modification in cancer cells has been associated with rapid cell division, tumor growth, cancer progression, and drug resistance. The higher rates of glycolysis in cancer cells, as a hallmark of cancer progression, is modulated by the transcription factor hypoxia inducible factor 1 alpha (HIF-1α), a downstream target of the PI3K/Akt signaling, the most deregulated pathway in cancer. AIM OF REVIEW: We provide a detailed overview of current, primarily experimental, evidence on the potential effectiveness of flavonoids to combat aberrant glycolysis-induced resistance of cancer cells to conventional and targeted therapies. The manuscript focuses primarily on flavonoids reducing cancer resistance via affecting PI3K/Akt, HIF-1α (as the transcription factor critical for glucose metabolism of cancer cells that is regulated by PI3K/Akt pathway), and key glycolytic mediators downstream of PI3K/Akt/HIF-1α signaling (glucose transporters and key glycolytic enzymes). KEY SCIENTIFIC CONCEPTS OF REVIEW: The working hypothesis of the manuscript proposes HIF-1α - the transcription factor critical for glucose metabolism of cancer cells regulated by PI3K/Akt pathway as an attractive target for application of flavonoids to mitigate cancer resistance. Phytochemicals represent a source of promising substances for cancer management applicable to primary, secondary, and tertiary care. However, accurate patient stratification and individualized patient profiling represent crucial steps in the paradigm shift from reactive to predictive, preventive, and personalized medicine (PPPM / 3PM). The article is focused on targeting molecular patterns by natural substances and provides evidence-based recommendations for the 3PM relevant implementation.
- Klíčová slova
- Cancer, Flavonoids, Glycolysis, Health-to-disease transition, Primary secondary tertiary care, Resistance, WHO, predictive preventive personalized medicine (PPPM / 3PM),
- MeSH
- flavonoidy MeSH
- fosfatidylinositol-3-kinasy metabolismus MeSH
- glukosa metabolismus MeSH
- individualizovaná medicína MeSH
- lidé MeSH
- nádorové mikroprostředí MeSH
- nádory * farmakoterapie metabolismus MeSH
- protoonkogenní proteiny c-akt * metabolismus MeSH
- signální transdukce MeSH
- transkripční faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- flavonoidy MeSH
- fosfatidylinositol-3-kinasy MeSH
- glukosa MeSH
- protoonkogenní proteiny c-akt * MeSH
- transkripční faktory MeSH
BACKGROUND: Synaptic dysfunction is a major contributor to Alzheimeŕs disease (AD) pathogenesis in addition to the formation of neuritic β-amyloid plaques and neurofibrillary tangles of hyperphosphorylated Tau protein. However, how these features contribute to synaptic dysfunction and axonal loss remains unclear. While years of considerable effort have been devoted to gaining an improved understanding of this devastating disease, the unavailability of patient-derived tissues, considerable genetic heterogeneity, and lack of animal models that faithfully recapitulate human AD have hampered the development of effective treatment options. Ongoing progress in human induced pluripotent stem cell (hiPSC) technology has permitted the derivation of patient- and disease-specific stem cells with unlimited self-renewal capacity. These cells can differentiate into AD-affected cell types, which support studies of disease mechanisms, drug discovery, and the development of cell replacement therapies in traditional and advanced cell culture models. AIM OF REVIEW: To summarize current hiPSC-based AD models, highlighting the associated achievements and challenges with a primary focus on neuron and synapse loss. KEY SCIENTIFIC CONCEPTS OF REVIEW: We aim to identify how hiPSC models can contribute to understanding AD-associated synaptic dysfunction and axonal loss. hiPSC-derived neural cells, astrocytes, and microglia, as well as more sophisticated cellular organoids, may represent reliable models to investigate AD and identify early markers of AD-associated neural degeneration.
- Klíčová slova
- Alzheimer's disease, Astrocytes, Brain organoids, Induced pluripotent stem cells, Microglia, Neural differentiation, Neuronal loss, Neurons,
- MeSH
- Alzheimerova nemoc * genetika metabolismus patologie MeSH
- amyloidní beta-protein genetika metabolismus MeSH
- indukované pluripotentní kmenové buňky * metabolismus patologie MeSH
- lidé MeSH
- neurony metabolismus MeSH
- synapse metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- amyloidní beta-protein MeSH
INTRODUCTION: Meiotic recombination is one of the most important processes of evolution and adaptation to environmental conditions. Even though there is substantial knowledge about proteins involved in the process, targeting specific DNA loci by the recombination machinery is not well understood. OBJECTIVES: This study aims to investigate a wheat recombination hotspot (H1) in comparison with a "regular" recombination site (Rec7) on the sequence and epigenetic level in conditions with functional and non-functional Ph1 locus. METHODS: The DNA sequence, methylation pattern, and recombination frequency were analyzed for the H1 and Rec7 in three mapping populations derived by crossing introgressive wheat line 8.1 with cv. Chinese Spring (with Ph1 and ph1 alleles) and cv. Tähti. RESULTS: The H1 and Rec7 loci are 1.586 kb and 2.538 kb long, respectively. High-density mapping allowed to delimit the Rec7 and H1 to 19 and 574 bp and 593 and 571 bp CO sites, respectively. A new method (ddPing) allowed screening recombination frequency in almost 66 thousand gametes. The screening revealed a 5.94-fold higher recombination frequency at the H1 compared to the Rec7. The H1 was also found out of the Ph1 control, similarly as gamete distortion. The recombination was strongly affected by larger genomic rearrangements but not by the SNP proximity. Moreover, chromatin markers for open chromatin and DNA hypomethylation were found associated with crossover occurrence except for the CHH methylation. CONCLUSION: Our results, for the first time, allowed study of wheat recombination directly on sequence, shed new light on chromatin landmarks associated with particular recombination sites, and deepened knowledge about role of the Ph1 locus in control of wheat recombination processes. The results are suggesting more than one recombination control pathway. Understanding this phenomenon may become a base for more efficient wheat genome manipulation, gene pool enrichment, breeding, and study processes of recombination itself.
- Klíčová slova
- Crossovers, DNA methylation, Hotspot, Ph1 locus, Recombination, Wheat,
- MeSH
- chromatin * genetika MeSH
- chromozomy MeSH
- DNA MeSH
- pšenice * genetika MeSH
- šlechtění rostlin MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- chromatin * MeSH
- DNA MeSH
INTRODUCTION: The Industrial Internet of Water Things (IIoWT) has recently emerged as a leading architecture for efficient water distribution in smart cities. Its primary purpose is to ensure high-quality drinking water for various institutions and households. However, existing IIoWT architecture has many challenges. One of the paramount challenges in achieving data standardization and data fusion across multiple monitoring institutions responsible for assessing water quality and quantity. OBJECTIVE: This paper introduces the Industrial Internet of Water Things System for Data Standardization based on Blockchain and Digital Twin Technology. The main objective of this study is to design a new IIoWT architecture where data standardization, interoperability, and data security among different water institutions must be met. METHODS: We devise the digital twin-enabled cross-platform environment using the Message Queuing Telemetry Transport (MQTT) protocol to achieve seamless interoperability in heterogeneous computing. In water management, we encounter different types of data from various sensors. Therefore, we propose a CNN-LSTM and blockchain data transactional (BCDT) scheme for processing valid data across different nodes. RESULTS: Through simulation results, we demonstrate that the proposed IIoWT architecture significantly reduces processing time while improving the accuracy of data standardization within the water distribution management system. CONCLUSION: Overall, this paper presents a comprehensive approach to tackle the challenges of data standardization and security in the IIoWT architecture.
- Klíčová slova
- Blockchain, Data modality and standardization, Digital twin, IIoWT, Transparency, Water management,
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Tumor necrosis factor-alpha (TNF-α) agonists revolutionized therapeutic algorithms in inflammatory bowel disease (IBD) management. However, approximately every third IBD patient does not respond to this therapy in the long term, which delays efficient control of the intestinal inflammation. METHODS: We analyzed the power of serum biomarkers to predict the failure of anti-TNF-α. We collected serum of 38 IBD patients at therapy prescription and 38 weeks later and analyzed them with relation to therapy response (no-, partial-, and full response). We used enzyme-linked immunosorbent assay to quantify 16 biomarkers related to gut barrier (intestinal fatty acid-binding protein, liver fatty acid-binding protein, trefoil factor 3, and interleukin (IL)-33), microbial translocation, immune system regulation (TNF-α, CD14, lipopolysaccharide-binding protein, mannan-binding lectin, IL-18, transforming growth factor-β1 (TGF-β1), osteoprotegerin (OPG), insulin-like growth factor 2 (IGF-2), endocrine-gland-derived vascular endothelial growth factor), and matrix metalloproteinase system (MMP-9, MMP-14, and tissue inhibitors of metalloproteinase-1). RESULTS: We found that future full-responders have different biomarker profiles than non-responders, while partial-responders cannot be distinguished from either group. When future non-responders were compared to responders, their baseline contained significantly more TGF-β1, less CD14, and increased level of MMP-9, and concentration of these factors could predict non-responders with high accuracy (AUC = 0.938). Interestingly, during the 38 weeks, levels of MMP-9 decreased in all patients, irrespective of the outcome, while OPG, IGF-2, and TGF-β1 were higher in non-responders compared to full-responders both at the beginning and the end of the treatment. CONCLUSIONS: The TGF-β1 and CD14 can distinguish non-responders from responders. The changes in biomarker dynamics during the therapy suggest that growth factors (such as OPG, IGF-2, and TGF-β) are not markedly influenced by the treatment and that anti-TNF-α therapy decreases MMP-9 without influencing the treatment outcome.
- MeSH
- inhibitory TNF MeSH
- insulinu podobný růstový faktor II * MeSH
- lidé MeSH
- matrixová metaloproteinasa 9 MeSH
- transformující růstový faktor beta1 * MeSH
- vaskulární endoteliální růstový faktor A MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- inhibitory TNF MeSH
- insulinu podobný růstový faktor II * MeSH
- matrixová metaloproteinasa 9 MeSH
- transformující růstový faktor beta1 * MeSH
- vaskulární endoteliální růstový faktor A MeSH
BACKGROUND: The QuantiFERON®-Monitor (QFM) is an assay that measures interferon-γ production and was developed to provide an objective marker of complex immune response. In this study, we evaluated the use of the QFM test in patients with two forms of multiple sclerosis (MS), relapsing-remitting form treated with fingolimod (fMS) and secondarily progressive form not treated pharmacologically (pMS), and in healthy controls (HC). We hypothesized that IFN-γ levels would be lower in those subjects who are relatively more immunosuppressed and higher in those with normal or activated immune function. METHODS: This single-center observational study was conducted from November 2020 to October 2021 and compared results in three groups of patients: 86 healthy controls, 96 patients with pMS, and 78 fMS. Combination of lyophilized stimulants was added to 1 ml heparinized whole blood within 8 hr of collection. Plasmatic IFN-γ was measured using the ELISA kit for the QFM and data were obtained in IU/ml. RESULTS: The results showed that controls had nearly 2-fold higher levels of IFN-γ (QFM score) in median (q25, q75) 228.00 (112.20, 358.67) than the MS patient groups: pMS 144.80 (31.23, 302.00); fMS 130.50 (39.95, 217.07) which is statistically significant difference P-value: HC vs. pMS = 0.0071; HC vs. fMS = 0.0468. This result was also confirmed by a validation analysis to exclude impact of variable factors, such as disease duration and Expanded Disability Status Scale scores. CONCLUSIONS: Results showed that controls had higher levels of IFN-γ production than the MS patient groups and suggest that MS patients included in this study have a lower ability of immune system activation than HC. Results confirm that fingolimod is able to suppress production of IFN-γ. The fact that the QFM score of MS patients is significantly lower than that of HC may indicate a dysfunctional state of the immune system in baseline conditions.
- MeSH
- ELISA MeSH
- fingolimod hydrochlorid terapeutické užití MeSH
- imunitní systém MeSH
- interferon gama MeSH
- lidé MeSH
- relabující-remitující roztroušená skleróza * MeSH
- roztroušená skleróza * diagnóza farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Názvy látek
- fingolimod hydrochlorid MeSH
- interferon gama MeSH
INTRODUCTION: Recent observations indicate that the Universe is not transparent but partially opaque due to absorption of light by ambient cosmic dust. This implies that the current cosmological model valid for the transparent universe must be modified for the opaque universe. OBJECTIVES: The paper studies a scenario of the evolution of the Universe when the cosmic opacity steeply rises with redshift, because the volume of the Universe was smaller and the cosmic dust density was higher in the previous epochs. In this case, the light-matter interactions become important, because cosmic opacity produces radiation pressure that counterbalances gravitational forces. METHODS: The radiation pressure due to cosmic opacity is evaluated and incorporated into the Friedmann equations, which describe cosmic dynamics. The equations are based on the conformal FLRW metric and are consistent with observations of the cosmological redshift as well as time dilation. Using astronomical observations of basic cosmological parameters, the solution of the modified Friedmann equations is numerically modelled. RESULTS: The presented model predicts a cyclic expansion/contraction evolution of the Universe within a limited range of scale factors with no Big Bang. The redshift of the Universe with the minimum volume is about 15-17. The model avoids dark energy and removes several fundamental tensions of the standard cosmological model. In agreement with observations, the modified Friedmann equations predict the existence of very old mature galaxies at high redshifts and they do not limit the age of stars in the Universe. The new model is consistent with theory of cosmic microwave background as thermal radiation of cosmic dust. CONCLUSION: The paper demonstrates that considering light-matter interactions in cosmic dynamics is crucial and can lead to new cosmological models essentially different from the currently accepted ΛCDM model.
- Klíčová slova
- Conformal metric, Cosmic dust, Cosmic opacity, Cyclic cosmology, Dark energy, Early Universe,
- Publikační typ
- časopisecké články MeSH
