78 research outputs found

    Protein Carbonylation of an Amino Acid Residue of the Na/Kā€ATPase Ī±1 Subunit Determines Na/Kā€ATPase Signaling and Sodium Transport in Renal Proximal Tubular Cells

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    Background We have demonstrated that cardiotonic steroids, such as ouabain, signaling through the Na/Kā€ATPase, regulate sodium reabsorption in the renal proximal tubule. By direct carbonylation modification of the Pro222 residue in the actuator (A) domain of pig Na/Kā€ATPase Ī±1 subunit, reactive oxygen species are required for ouabainā€stimulated Na/Kā€ATPase/cā€Src signaling and subsequent regulation of active transepithelial 22Na+ transport. In the present study we sought to determine the functional role of Pro222 carbonylation in Na/Kā€ATPase signaling and sodium handling. Methods and Results Stable pig Ī±1 knockdown LLCā€PK1ā€originated PYā€17 cells were rescued by expressing wildā€type rat Ī±1 and rat Ī±1 with a single mutation of Pro224 (corresponding to pig Pro222) to Ala. This mutation does not affect ouabainā€induced inhibition of Na/Kā€ATPase activity, but abolishes the effects of ouabain on Na/Kā€ATPase/cā€Src signaling, protein carbonylation, Na/Kā€ATPase endocytosis, and active transepithelial 22Na+ transport. Conclusions Direct carbonylation modification of Pro224 in the rat Ī±1 subunit determines ouabainā€mediated Na/Kā€ATPase signal transduction and subsequent regulation of renal proximal tubule sodium transport

    Physician privacy concerns when disclosing patient data for public health purposes during a pandemic influenza outbreak

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    Background: Privacy concerns by providers have been a barrier to disclosing patient information for public health\ud purposes. This is the case even for mandated notifiable disease reporting. In the context of a pandemic it has been\ud argued that the public good should supersede an individualā€™s right to privacy. The precise nature of these provider\ud privacy concerns, and whether they are diluted in the context of a pandemic are not known. Our objective was to\ud understand the privacy barriers which could potentially influence family physiciansā€™ reporting of patient-level\ud surveillance data to public health agencies during the Fall 2009 pandemic H1N1 influenza outbreak.\ud Methods: Thirty seven family doctors participated in a series of five focus groups between October 29-31 2009.\ud They also completed a survey about the data they were willing to disclose to public health units. Descriptive\ud statistics were used to summarize the amount of patient detail the participants were willing to disclose, factors that\ud would facilitate data disclosure, and the consensus on those factors. The analysis of the qualitative data was based\ud on grounded theory.\ud Results: The family doctors were reluctant to disclose patient data to public health units. This was due to concerns\ud about the extent to which public health agencies are dependable to protect health information (trusting beliefs),\ud and the possibility of loss due to disclosing health information (risk beliefs). We identified six specific actions that\ud public health units can take which would affect these beliefs, and potentially increase the willingness to disclose\ud patient information for public health purposes.\ud Conclusions: The uncertainty surrounding a pandemic of a new strain of influenza has not changed the privacy\ud concerns of physicians about disclosing patient data. It is important to address these concerns to ensure reliable\ud reporting during future outbreaks.University of Ottawa Open Access Author Fun

    On the typology and the worship status of sacred trees with a special reference to the Middle East

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    This article contains the reasons for the establishment of sacred trees in Israel based on a field study. It includes 97 interviews with Muslim and Druze informants. While Muslims (Arabs and Bedouins) consider sacred trees especially as an abode of righteous figures' (Wellis') souls or as having a connection to their graves, the Druze relate sacred trees especially to the events or deeds in the lives of prophets and religious leaders. A literary review shows the existence of 24 known reasons for the establishment of sacred trees worldwide, 11 of which are known in Israel one of these is reported here for the first time. We found different trends in monotheistic and polytheistic religions concerning their current worship of sacred trees

    Triple-GEM discharge probability studies at CHARM: Simulations and experimental results

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    The CMS muon system in the region with 2.03<|Ī·|<2.82 is characterized by a very harsh radiation environment which can generate hit rates up to 144 kHz/cm2^{2} and an integrated charge of 8 C/cm2^{2} over ten years of operation. In order to increase the detector performance and acceptance for physics events including muons, a new muon station (ME0) has been proposed for installation in that region. The technology proposed is Tripleā€”Gas Electron Multiplier (Triple-GEM), which has already been qualified for the operation in the CMS muon system. However, an additional set of studies focused on the discharge probability is necessary for the ME0 station, because of the large radiation environment mentioned above. A test was carried out in 2017 at the Cern High energy AcceleRator Mixed (CHARM) facility, with the aim of giving an estimation of the discharge probability of Triple-GEM detectors in a very intense radiation field environment, similar to the one of the CMS muon system. A dedicated standalone Geant4 simulation was performed simultaneously, to evaluate the behavior expected in the detector exposed to the CHARM field. The geometry of the detector has been carefully reproduced, as well as the background field present in the facility. This paper presents the results obtained from the Geant4 simulation, in terms of sensitivity of the detector to the CHARM environment, together with the analysis of the energy deposited in the gaps and of the processes developed inside the detector. The discharge probability test performed at CHARM will be presented, with a complete discussion of the results obtained, which turn out to be consistent with measurements performed by other groups

    Detector Control System for the GE1/1 slice test

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    Gas Electron Multiplier (GEM) technology, in particular triple-GEM, was selected for the upgrade of the CMS endcap muon system following several years of intense effort on R&D. The triple-GEM chambers (GE1/1) are being installed at station 1 during the second long shutdown with the goal of reducing the Level-1 muon trigger rate and improving the tracking performance in the harsh radiation environment foreseen in the future LHC operation [1]. A first installation of a demonstrator system started at the beginning of 2017: 10 triple-GEM detectors were installed in the CMS muon system with the aim of gaining operational experience and demonstrating the integration of the GE1/1 system into the trigger. In this context, a dedicated Detector Control System (DCS) has been developed, to control and monitor the detectors installed and integrating them into the CMS operation. This paper presents the slice test DCS, describing in detail the different parts of the system and their implementation

    Putting the treatment of paediatric schistosomiasis into context

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    Abstract Despite increased international efforts to control schistosomiasis using preventive chemotherapy, several challenges still exist in reaching the target populations. Until recently, preschool-aged children had been excluded from the recommended target population for mass drug administration, i.e. primary school children aged 6ā€“15 years. Our studies and those of others provided the evidence base for the need to treat preschool-aged children that led to recommendations by the World Health Organization to include preschool-aged children in treatment programmes in 2010. The major challenge now lies in the unavailability of a child-size formulation of the appropriate anthelmintic drug, praziquantel. The currently available formulation of praziquantel presents several problems. First, it is a large tablet, making it difficult for young children and infants to swallow it and thus requires its breaking/crushing to allow for safe uptake. Second, it is bitter so it is often mixed with a sweetener to make it palatable for young children. Third, the current formulation of 600Ā mg does not allow for flexible dose adjustments for this age group. Thus, there is a need to formulate a child-appropriate praziquantel tablet. This paper discusses the target product profile for paediatric praziquantel, as well as knowledge gaps pertinent to the successful control of schistosome infection and disease in preschool-aged children

    Complications of keratosis obturans

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