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  • Little Lindahl posted an update 4 days, 8 hours ago

    This paper investigates the impact of heterogeneity of the transmissivity field on the interpretation of steady-state pumping test data from aquifer systems delimited by constant head boundaries such as aquifers adjacent to lakes or rivers. Spatially variable transmissivity fields are randomly generated and used to simulate the drawdown due to a pumping well located at different distances from a constant head boundary. The steady-state drawdown simulated at different observation wells are then interpreted using the Hantush method (Hantush 1959). The numerical simulations show that, in contrast to the case of infinite aquifer domains, the interpreted transmissivity varies depending on well locations and the separation distance between pumping well and boundary relative to the correlation length. The ensemble-averaged estimated transmissivity varies between the geometric mean and the arithmetic mean, and can even exceed the arithmetic mean in a narrow domain adjacent to the boundary. It approaches the geometric mean of the underlying transmissivity field only if the distance between the pumping well is more than 20 times the characteristic length of the transmissivity field.Although cyclooxygenase (COX) role in cancer angiogenesis has been studied, little is known about its role in brain angioplasticity. In the present study, we chronically infused mice with ketorolac, a non-specific COX inhibitor that does not cross the blood-brain barrier (BBB), under normoxia or 50% isobaric hypoxia (10% O2 by volume). Novobiocin Antineoplastic and Immunosuppressive Antibiotics inhibitor Ketorolac increased mortality rate under hypoxia in a dose-dependent manner. Using in vivo multiphoton microscopy, we demonstrated that chronic COX inhibition completely attenuated brain angiogenic response to hypoxia. Alterations in a number of angiogenic factors that were reported to be COX-dependent in other models were assayed at 24-hr and 10-day hypoxia. Intriguingly, hypoxia-inducible factor 1 was unaffected under COX inhibition, and vascular endothelial growth factor receptor type 2 (VEGFR2) and C-X-C chemokine receptor type 4 (CXCR4) were significantly but slightly decreased. However, a number of mitogen-activated protein kinases (MAPKs) were significantly reduced upon COX inhibition. We conclude that additional, angiogenic factor-independent mechanism might contribute to COX role in brain angioplasticity, probably including mitogenic COX effect on endothelium. Our data indicate that COX activity is critical for systemic adaptation to chronic hypoxia, and BBB COX is essential for hypoxia-induced brain angioplasticity. These data also indicate a potential risk for using COX inhibitors under hypoxia conditions in clinics. Further studies are required to elucidate a complete mechanism for brain long-term angiogenesis regulation through COX activity.Bioactive glasses (BAG) are used as bone-graft substitutes in orthopaedic surgery. A specific BAG scaffold was developed by sintering BAG-S53P4 granules. It is hypothesised that this scaffold can be used as a bone substitute to fill bone defects and induce a bioactive membrane (IM) around the defect site. Beyond providing the scaffold increased mechanical strength, that the initial inflammatory reaction and subsequent IM formation can be enhanced by coating the scaffolds with poly(DL-lactide-co-glycolide) (PLGA) is also hypothesised. To study the immunomodulatory effects, BAG-S53P4 (± PLGA) scaffolds were placed on monolayers of primary human macrophage cultures and the production of various pro- and anti-inflammatory cytokines was assessed using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and ELISA. To study the osteogenic effects, BAG-S53P4 (± PLGA) scaffolds were cultured with rabbit mesenchymal stem cells and osteogenic differentiation was evaluated by RT-qPCR and matrix mineralisation assays. The scaffold ion release was quantified and the BAG surface reactivity visualised. Furthermore, the pH of culture media was measured. BAG-S53P4 scaffolds had both anti-inflammatory and osteogenic properties that were likely attributable to alkalinisation of the media and ion release from the scaffold. pH change, ion release, and immunomodulatory properties of the scaffold could be modulated by the PLGA coating. Contrary to the hypothesis, the coating functioned by attenuating the BAG surface reactions and subsequent anti-inflammatory properties, rather than inducing an elevated inflammatory response compared to BAG-S53P4 alone. These results further validated the use of BAG-S53P4 (± PLGA) scaffolds as bone substitutes and indicate that scaffold properties can be tailored to a specific clinical need.Chromoblastomycosis and phaeohyphomycosis are less common fungal infections caused by dark-pigmented fungi. Virulence factors play an important role in the pathogenesis of these diseases. One of these factors, muriform cells, are the most important element for differential diagnosis of chromoblastomycosis and phaeohyphomycosis using clinical samples and various staining techniques. Accurate identification of pathogens causing chromoblastomycosis and phaeohyphomycosis is very important for correct and early antifungal therapy. Therefore, species identification of the etiological agent should be confirmed by sequencing of DNA from the culture. Early diagnosis may be crucial, especially in case of invasive forms of these infections. The diagnosis may be guided by some immunohistochemistry methods and DNA detection using polymerase chain reaction directly from clinical samples seems to be useful for identification of pathogens causing these severe and life-threatening infections.Cases of chromoblastomycosis are frequent in certain parts of the world, especially in some developing countries. Clinical manifestations of chromoblastomycosis are typical. To a certain extent, pathogens causing chromoblastomycosis overlap with those causing phaeohyphomycosis. Although cases of phaeohyphomycosis are not very common, they may end fatally. Therefore early management of these life-threatening infections is rather important. Targeted antifungal therapy and surgery are effective in combating these infections. Recently, several triazole antifungals such as posaconazole and isavuconazole have been available to treat even the most severe cases. Prevention of the infection should be aimed at reducing the risk of subcutaneous trauma, particularly in persons in contact with potential sources of infection such as wood materials important from endemic areas.

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