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Hjelm McQueen posted an update 6 months, 2 weeks ago
An association of AMU and AMR was observed for resistance to tetracycline and erythromycin, while it was not observed for the aminoglycosides. Resistance to nalidixic acid and ciprofloxacin increased despite a decrease of fluoroquinolone use between 2014 and 2016, indicating that other factors have a strong influence on resistance to (fluoro)quinolones in Campylobacter.The natural product elaiophylin is a macrodiolide with a broad range of biological activities. However, no direct target of elaiophylin in eukaryotes has been described so far, which hinders a systematic explanation of its astonishing activity range. We recently showed that the related conglobatin A, a protein-protein interface inhibitor of the interaction between the N-terminus of Hsp90 and its cochaperone Cdc37, blocks cancer stem cell properties by selectively inhibiting K-Ras4B but not H-Ras. Here, we elaborated that elaiophylin likewise disrupts the Hsp90/ Cdc37 interaction, without affecting the ATP-pocket of Hsp90. Similarly to conglobatin A, elaiophylin decreased expression levels of the Hsp90 client HIF1α, a transcription factor with various downstream targets, including galectin-3. Galectin-3 is a nanocluster scaffold of K-Ras, which explains the K-Ras selectivity of Hsp90 inhibitors. In agreement with this K-Ras targeting and the potent effect on other Hsp90 clients, we observed with elaiophylin treatment a submicromolar IC50 for MDA-MB-231 and MIA-PaCa-2 3D spheroid formation. Finally, a strong inhibition of MDA-MB-231 cells grown in the chorioallantoic membrane (CAM) microtumor model was determined. These results suggest that several other macrodiolides may have the Hsp90/ Cdc37 interface as a target site.The objective of this study was to determine the intrinsic drug dissolution rate (IDR) and the solute effective transport rate of some drugs, using a single particle dissolution technique, satisfying qualified dissolution conditions. The IDR of three poorly water-soluble compounds was measured in milli-Q water using four different fluid velocities. The enveloped surface area of the particles was calculated from the projected area and the perimeter of the particle observed in the microscope. Furthermore, computational fluid dynamics (CFD) simulations were used to theoretically investigate the flow conditions and dissolution rate, comparing box shaped particles and spherical particles with similar dimensions and surface area as the particles used the experiments. In this study, the IDR measurement of the single particles was determined within 5-60 min using particles with an initial projected area diameter (Dp) between 37.5-104.6 µm. The micropipette-assisted microscopy technique showed a good reproducibility between individual measurements, and the CFD simulations indicated a laminar flow around the particles at all flow velocities, even though there were evident differences in local particle dissolution rates. In conclusion, the IDR and solute effective transport rate were determined under well-defined fluid flow conditions. This type of approach can be used as a complementary approach to traditional dissolution studies to gain in-depth insights into the dissolution process of drug particles.This article explores how multiple health risks in municipalities with Roma settlements in Slovakia are related to the varieties of local governance and the authorities’ conduct towards the local Roma population. The first part of the paper describes the situation in Roma settlements from the perspective of unequal access to sewerage and water pipelines. Introduced here are data on identified contagious diseases that correlated multiple health risks with the lack of sanitation and/or water infrastructure. The second section of the paper put forth typologies of government approaches towards the Roma, which based on ethnographic fieldwork, allows us to identify factors of attitudinal, structural and policy-oriented nature. Research results point to a “triad” of key circumstances these are the structural conditions in municipalities and the history of local inter-ethnic relations and attitude of authorities towards Roma. buy GI254023X Finally, possible solutions and approaches regarding how to mitigate the multiple health risks are discussed. It is suggested that on the one hand, in many villages there is a profound institutional discrimination of Roma with respect to water and sanitation infrastructure; on the other hand, water services are increasingly becoming an expensive commodity that not everyone can afford. The article concludes with discussion on enabling conditions and ways to ensure access to basic infrastructure in rural Roma communities. The solution is not only a compliance with principles of non-discrimination and existing technical norms and standards but also in securing the accessible funding for construction of the sanitation infrastructure in a smart way, including innovations and operation of cheaper and environmentally responsible sanitation technologies.Titanium (Ti) alloys have been proven to be one of the most suitable materials for orthopaedic implants. Dual modular stems have been introduced to primary total hip arthroplasty (THA) to enable better control of the femoral offset, leg length, and hip stability. This systematic review highlights information acquired for dual modular Ti stem complications published in the last 12 years and offers a conclusive discussion of the gathered knowledge. Articles referring to dual modular stem usage, survivorship, and complications in English were searched from 2009 to the present day. A qualitative synthesis of literature was carried out, excluding articles referring solely to other types of junctions or problems with cobalt-chromium alloys in detail. In total, 515 records were identified through database searching and 78 journal articles or conference proceedings were found. The reasons for a modular neck fracture of a Ti alloy are multifactorial. Even though dual modular stems have not shown any clinical benefits for patients and have been associated with worse results regarding durability than monolithic stems, some designs are still marketed worldwide. Orthopaedic surgeons should use Ti6Al4V dual modular stem designs for primary THA in special cases only.