Hypertension-induced renal fibrosis and spironolactone response vary by rat strain and mineralocorticoid receptor gene expression

Introduction. Aldosterone promotes renal fibrosis via the mineralocorticoid receptor (MR), thus contributing to hypertension-induced nephropathy. We investigated whether MR gene expression influences renal fibrosis and MR antagonist response in a two-kidney, one-clip hypertensive rat model. Materials and methods. Brown Norway (BN), Lewis, and ACI rats were randomised to spironolactone 20 mg/kg/day or water by gavage, starting four weeks after left renal artery clipping. Blood pressure was measured bi-weekly by tail cuff. After eight weeks of treatment, right kidneys were removed and examined for fibrosis and gene expression. Rats of each strain undergoing no intervention served as controls. Results. Blood pressure increased similarly among strains after clipping and was unaffected by spironolactone. Hypertension caused the greatest renal fibrosis in BN rats (p \u3c 0.001 by ANOVA compared to other strains). Real-time PCR analysis showed greater renal collagen type I and MR gene expression in untreated, hypertensive BN rats (both p \u3c 0.05 compared to other strains). Spironolactone attenuated fibrosis, with similar fibrosis among strains of spironolactone-treated rats. Conclusion. Hypertension-induced renal fibrosis was greatest in rats with the highest MR gene expression. Spironolactone abolished inter-strain differences in fibrosis. Our data suggest that MR genotype may influence aldosterone-induced renal damage, and consequently, renal response to aldosterone antagonism

Physical and psychological paths toward less severe fibromyalgia: A structural equation model

The authors gratefully acknowledge all the participants for their collaboration and enthusiasm. We thank the assistant researchers involved in this study and all the members of the Physical Activity for HEaLth Promotion (PA-HELP; CTS-1018) research group.Supplementary data associated with this article can be found, in the online version, at https://doi.org/10.1016/j.rehab.2019.06.017.Objectives: Previous research suggested isolated associations of physical and psychological factors with fibromyalgia severity. Integration of physical and psychological, experienced and observed, modifiable factors associated with fibromyalgia severity in a single model will reveal therapeutic paths toward less severity of disease. We aimed to examine an encompassing model of determinants of fibromyalgia severity. Methods: This observational, population-based cross-sectional study included 569 people with fibromyalgia. An integrative model of fibromyalgia severity was tested by using structural equation modelling. This model included 8 factors: resilience, catastrophizing, active lifestyle, declarative memory, subjective fitness, objective fitness, psychological distress, and physical fatigue. Results: Two core paths were associated with reduced fibromyalgia severity: 1) a psychological path connecting high resilience and low catastrophizing with low distress and 2) a physical path, connecting a more active lifestyle (directly and via high objective and subjective physical fitness) with low fatigue. Additional interconnecting paths especially suggested a connection from the psychological to physical path. Our model explained 83% of the fibromyalgia severity. Conclusions: The present model integrated the complexity of mutually influencing factors of fibromyalgia severity, which may help to better understand the disease. It emphasised the importance of: 1) physical factors and psychological factors and their interconnections, 2) patients’ experiences and clinical measurements, and 3) positive and negative signs such as physical fitness and distress. Future longitudinal and experimental research should aim at testing the causal direction of the associations in the model as well as the clinical implications suggested by the model. For instance, to reduce fatigue, exercise should enhance not only objective fitness but also fitness-related perceptions. Reducing distress and fatigue seems crucial for lowering fibromyalgia severity.This work was supported by the Spanish Ministry of Economy and Competitiveness [I+D+i DEP2010-15639, I+D+I DEP2013-40908, I+D+I PSI2015-65241-R, and BES-2014-067612] and the Spanish Ministry of Education [FPU15/00002]. This study was funded in part by the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES), and the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades and European Regional Development Fund (ref. SOMM17/6107/UGR) and University of Jaén, Plan de Apoyo a la Investigación 2017-2019 [EI_SEJ07_2017]. The funders did not have any role in the study design, data collection and analyses, decision to publish, or preparation of the manuscript

Risk Factors for Post-ERCP Pancreatitis: A Prospective Multicenter Study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75082/1/j.1572-0241.2006.00380.x.pd

On the selection of AGN neutrino source candidates for a source stacking analysis with neutrino telescopes

The sensitivity of a search for sources of TeV neutrinos can be improved by grouping potential sources together into generic classes in a procedure that is known as source stacking. In this paper, we define catalogs of Active Galactic Nuclei (AGN) and use them to perform a source stacking analysis. The grouping of AGN into classes is done in two steps: first, AGN classes are defined, then, sources to be stacked are selected assuming that a potential neutrino flux is linearly correlated with the photon luminosity in a certain energy band (radio, IR, optical, keV, GeV, TeV). Lacking any secure detailed knowledge on neutrino production in AGN, this correlation is motivated by hadronic AGN models, as briefly reviewed in this paper. The source stacking search for neutrinos from generic AGN classes is illustrated using the data collected by the AMANDA-II high energy neutrino detector during the year 2000. No significant excess for any of the suggested groups was found.Comment: 43 pages, 12 figures, accepted by Astroparticle Physic

Limits on the high-energy gamma and neutrino fluxes from the SGR 1806-20 giant flare of December 27th, 2004 with the AMANDA-II detector

On December 27th 2004, a giant gamma flare from the Soft Gamma-ray Repeater 1806-20 saturated many satellite gamma-ray detectors. This event was by more than two orders of magnitude the brightest cosmic transient ever observed. If the gamma emission extends up to TeV energies with a hard power law energy spectrum, photo-produced muons could be observed in surface and underground arrays. Moreover, high-energy neutrinos could have been produced during the SGR giant flare if there were substantial baryonic outflow from the magnetar. These high-energy neutrinos would have also produced muons in an underground array. AMANDA-II was used to search for downgoing muons indicative of high-energy gammas and/or neutrinos. The data revealed no significant signal. The upper limit on the gamma flux at 90% CL is dN/dE < 0.05 (0.5) TeV^-1 m^-2 s^-1 for gamma=-1.47 (-2). Similarly, we set limits on the normalization constant of the high-energy neutrino emission of 0.4 (6.1) TeV^-1 m^-2 s^-1 for gamma=-1.47 (-2).Comment: 14 pages, 3 figure

Detection of Atmospheric Muon Neutrinos with the IceCube 9-String Detector

The IceCube neutrino detector is a cubic kilometer TeV to PeV neutrino detector under construction at the geographic South Pole. The dominant population of neutrinos detected in IceCube is due to meson decay in cosmic-ray air showers. These atmospheric neutrinos are relatively well-understood and serve as a calibration and verification tool for the new detector. In 2006, the detector was approximately 10% completed, and we report on data acquired from the detector in this configuration. We observe an atmospheric neutrino signal consistent with expectations, demonstrating that the IceCube detector is capable of identifying neutrino events. In the first 137.4 days of livetime, 234 neutrino candidates were selected with an expectation of 211 +/- 76.1(syst.) +/- 14.5(stat.) events from atmospheric neutrinos