344 research outputs found

    Historical and current aspects of angiovisualization methods in CАD (a literature review)

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    The aim of the work. To summarize and expand knowledge about current methods used for visualization of coronary arteries, their evolution, capabilities, effectiveness, indications for use, safety for patients, guided by the principles of evidence-based medicine. Coronary artery disease (CАD) is an extremely common clinical cardiovascular disease, which is caused by atherosclerosis of the subepicardial coronary arteries (CAs) and can have both acute and chronic course. The incidence of CАD is increasing every year and getting younger. CАD has not only a high morbidity rate, but also a high mortality rate. In Ukraine, mortality from CАD is the main cause of population mortality. Without timely diagnosis and effective treatment, myocardial infarction or sudden cardiac death may develop. It is possible to ascertain the etiological cause of myocardial ischemia only after visualization of the СAs. A practicing physician is able to visualize the СAs using X-ray contrast coronary angiography or contrast-enhanced computed tomography of the chest. СA visualization methods have been used in clinical practice for more than half a century. The hardware and software are constantly upgraded, the diagnostic options of these methods are improved and expanded, and recommendations regarding their use in general clinical practice are updated. The main task for clinicians is to confirm or rule out the presence of a СA atherosclerotic lesion, as well as to determine its localization, extent, degree of stenosis and its significance for coronary blood flow, the presence of СA calcification, collateral pathways, plaque composition and its internal structure. Only after identifying the anatomical and physiological aspects of the atherosclerotic process in СA, it is possible to choose the right strategy for the treatment of patients by a multidisciplinary heart team including pharmacological therapy, a method of cardiac revascularization, and measures for primary or secondary prevention. Conclusions. CАD is a common disease worldwide. Today, two methods of the CА visualization are available – invasive coronary angiography and non-invasive coronary CT angiography. Further research is needed on the efficacy and safety of different СA imaging methods in CAD. Better results of the diagnostic search depend on both the capabilities of the clinic hardware component and on the optimal sequence for diagnostic processes rationally constructed by physicians

    Cancer-associated mesothelial cells promote ovarian cancer chemoresistance through paracrine osteopontin signaling

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    Ovarian cancer is the leading cause of gynecological malignancy-related deaths, due to its widespread intraperitoneal metastases and acquired chemoresistance. Mesothelial cells are an important cellular component of the ovarian cancer microenvironment that promote metastasis. However, their role in chemoresistance is unclear. Here, we investigated whether cancer-associated mesothelial cells promote ovarian cancer chemoresistance and stemness in vitro and in vivo. We found that osteopontin is a key secreted factor that drives mesothelial-mediated ovarian cancer chemoresistance and stemness. Osteopontin is a secreted glycoprotein that is clinically associated with poor prognosis and chemoresistance in ovarian cancer. Mechanistically, ovarian cancer cells induced osteopontin expression and secretion by mesothelial cells through TGF-β signaling. Osteopontin facilitated ovarian cancer cell chemoresistance via the activation of the CD44 receptor, PI3K/AKT signaling, and ABC drug efflux transporter activity. Importantly, therapeutic inhibition of osteopontin markedly improved the efficacy of cisplatin in both human and mouse ovarian tumor xenografts. Collectively, our results highlight mesothelial cells as a key driver of ovarian cancer chemoresistance and suggest that therapeutic targeting of osteopontin may be an effective strategy for enhancing platinum sensitivity in ovarian cancer

    Stem Cell Based Drug Delivery for Protection of Auditory Neurons in a Guinea Pig Model of Cochlear Implantation

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    Background: The success of a cochlear implant (CI), which is the standard therapy for patients suffering from severe to profound sensorineural hearing loss, depends on the number and excitability of spiral ganglion neurons (SGNs). Brain-derived neurotrophic factor (BDNF) has a protective effect on SGNs but should be applied chronically to guarantee their lifelong survival. Long-term administration of BDNF could be achieved using genetically modified mesenchymal stem cells (MSCs), but these cells should be protected – by ultra-high viscous (UHV-) alginate (‘alginate-MSCs’) – from the recipient immune system and from uncontrolled migration.Methods: Brain-derived neurotrophic factor-producing MSCs were encapsulated in UHV-alginate. Four experimental groups were investigated using guinea pigs as an animal model. Three of them were systemically deafened and (unilaterally) received one of the following: (I) a CI; (II) an alginate-MSC-coated CI; (III) an injection of alginate-embedded MSCs into the scala tympani followed by CI insertion and alginate polymerization. Group IV was normal hearing, with CI insertion in both ears and a unilateral injection of alginate-MSCs. Using acoustically evoked auditory brainstem response measurements, hearing thresholds were determined before implantation and before sacrificing the animals. Electrode impedance was measured weekly. Four weeks after implantation, the animals were sacrificed and the SGN density and degree of fibrosis were evaluated.Results: The MSCs survived being implanted for 4 weeks in vivo. Neither the alginate-MSC injection nor the coating affected electrode impedance or fibrosis. CI insertion with and without previous alginate injection in normal-hearing animals resulted in increased hearing thresholds within the high-frequency range. Low-frequency hearing loss was additionally observed in the alginate-injected and implanted cochleae, but not in those treated only with a CI. In deafened animals, the alginate-MSC coating of the CI significantly prevented SGN from degeneration, but the injection of alginate-MSCs did not.Conclusion: Brain-derived neurotrophic factor-producing MSCs encapsulated in UHV-alginate prevent SGNs from degeneration in the form of coating on the CI surface, but not in the form of an injection. No increase in fibrosis or impedance was detected. Further research and development aimed at verifying long-term mechanical and biological properties of coated electrodes in vitro and in vivo, in combination with chronic electrical stimulation, is needed before the current concept can be tested in clinical trials

    Host-driven subspeciation in the hedgehog fungus, Trichophyton erinacei, an emerging cause of human dermatophytosis

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    Altres ajuts: Czech Ministry of Health (grant NU21-05-00681)Trichophyton erinacei is a main cause of dermatophytosis in hedgehogs and is increasingly reported from human infections worldwide. This pathogen was originally described in the European hedgehog (Erinaceus europaeus) but is also frequently found in the African four-toed hedgehog (Atelerix albiventris), a popular pet animal worldwide. Little is known about the taxonomy and population genetics of this pathogen despite its increasing importance in clinical practice. Notably, whether there are different populations or even cryptic species associated with different hosts or geographic regions is not known. To answer these questions, we collected 161 isolates, performed phylogenetic and population-genetic analyses, determined mating-type, and characterised morphology and physiology. Multigene phylogeny and microsatellite analysis supported T. erinacei as a monophyletic species, in contrast to highly incongruent single-gene phylogenies. Two main subpopulations, one specific mainly to Atelerix and second to Erinaceus hosts, were identified inside T. erinacei, and slight differences in the size of microconidia and antifungal susceptibilities were observed among them. Although the process of speciation into two lineages is ongoing in T. erinacei, there is still gene flow between these populations. Thus, we present T. erinacei as a single species, with notable intraspecies variability in genotype and phenotype. The data from wild hedgehogs indicated that sexual reproduction in T. erinacei and de novo infection of hedgehogs from soil are probably rare events and that clonal horizontal spread strongly dominates. The molecular typing approach used in this study represents a suitable tool for further epidemiological surveillance of this emerging pathogen in both animals and humans. The results of this study also highlighted the need to use a multigene phylogeny ideally in combination with other inde-pendent molecular markers to understand the species boundaries of dermatophytes

    A systematic review of protocol studies on conceptual design cognition

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    This paper reports the first systematic review and synthesis of protocol studies on conceptual design cognition. 47 protocol studies from the domains of architectural design, engineering design, and product de-sign engineering were reviewed towards answering the following re-search question: What is our current understanding of the cognitive processes involved in conceptual design tasks carried out by individual designers? Studies were found to reflect three viewpoints on the cognitive nature of designing, namely: design as search; design as ex-ploration; and design activities. Synthesising the findings of individual studies yielded a classification of cognitive processes involved in con-ceptual design tasks, described in different terms across different viewpoints. Towards a common terminology, these processes are posi-tioned within the cognitive psychology literature, revealing seven basic types of process that appear to be fundamental to designing across all viewpoints: memory (working and long term); visual perception; men-tal imagery; attention; semantic association; cognitive control; and higher-order processes, e.g. analysis and reasoning. The development of common cognitive models of conceptual design, grounded in a sci-entifically rigorous understanding of design cognition, is identified as an avenue for future research
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