2,998 research outputs found

    Bile‐duct ligation renders the brain susceptible to hypotension induced neuronal degeneration : implications of ammonia

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    Hepatic encephalopathy (HE) is a debilitating neurological complication of cirrhosis. By definition, HE is considered a reversible disorder, and therefore HE should resolve following liver transplantation (LT). However, persisting neurological complications are observed in as many as 47% of LT recipients. LT is an invasive surgical procedure accompanied with various perioperative factors such as blood loss and hypotension which could influence outcomes post‐LT. We hypothesize that minimal HE (MHE) renders the brain frail and susceptible to hypotension‐induced neuronal cell death. Six‐week bile duct‐ligated (BDL) rats with MHE and respective SHAM‐controls were used. Several degrees of hypotension (mean arterial pressure of 30, 60 and 90mmHg) were induced via blood withdrawal from the femoral artery and maintained for 120 minutes. Brains were collected for neuronal cell count and apoptotic analysis. In a separate group, BDL rats were treated for MHE with the ammonia‐lowering strategy ornithine phenylacetate (OP; MNK‐6105), administered orally (1g/kg) for 3 weeks before induction of hypotension. Hypotension 30 and 60mmHg (not 90mmHg) significantly decreased neuronal marker expression (NeuN) and cresyl violet staining in the frontal cortex compared to respective hypotensive SHAM‐operated controls as well as non‐hypotensive BDL rats. Neuronal degeneration was associated with an increase in cleaved caspase‐3, suggesting the mechanism of cell death was apoptotic. OP treatment attenuated hyperammonemia, improved anxiety and activity, and protected the brain against hypotension‐induced neuronal cell death. Our findings demonstrate that rats with chronic liver disease and MHE are more susceptible to hypotension‐induced neuronal cell degeneration. This highlights MHE at the time of LT is a risk factor for poor neurological outcome post‐transplant and that treating for MHE pre‐LT might reduce this risk

    Agricultura orgùnica no Brasil: sua trajetória para a certificação compulsória.

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    Este artigo apresenta um histórico a respeito da regulamentação da produção de orgùnicos no Brasil. São mencionados todos os documentos nacionais relevantes jå publicados em Diårio Oficial, destacando-se alguns deles conforme sua importùncia para o mercado de orgùnicos no Brasil

    An Evolutionary No Man’s Land and Reply from L. G. Harshman and A. A. Hoffmann

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    The gap between evolutionary studies in laboratory versus natural populations is a persistent problem

    flexsdm: An r package for supporting a comprehensive and flexible species distribution modelling workflow

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    Species distribution models (SDM) are widely used in diverse research areas because of their simple data requirements and application versatility. However, SDM outcomes are sensitive to data input and methodological choices. Such sensitivity and diverse applications mean that flexibility is necessary to create SDMs with tailored protocols for a given set of data and model use. We introduce the r package flexsdm for supporting flexible species distribution modelling workflows. flexsdm functions and their arguments serve as building blocks to construct a specific modelling protocol for user's needs. The main flexsdm features are modelling flexibility, integration with other modelling tools, simplicity of the objects returned and function speed. As an illustration, we used flexsdm to define a complete workflow for California red fir Abies magnifica. This package provides modelling flexibility by incorporating comprehensive tools structured in three steps: (a) The Pre-modelling functions that prepare input, for example, sampling bias correction, sampling pseudo-absences and background points, data partitioning, and reducing collinearity in predictors. (b) The Modelling functions allow fitting and evaluating different modelling approaches, including individual algorithms, tuned models, ensembles of small models and ensemble models. (c) The Post-modelling functions include tools related to models' predictions, interpolation and overprediction correction. Because flexsdm comprises a large part of the SDM process, from outlier detection to overprediction correction, flexsdm users can delineate partial or complete workflows based on the combination functions to meet specific modelling needs.Fil: Velazco, Santiago JosĂ© ElĂ­as. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Nordeste. Instituto de BiologĂ­a Subtropical. Instituto de BiologĂ­a Subtropical - Nodo Puerto IguazĂș | Universidad Nacional de Misiones. Instituto de BiologĂ­a Subtropical. Instituto de BiologĂ­a Subtropical - Nodo Puerto IguazĂș; Argentina. University of California; Estados Unidos. Universidade Federal da Integração Latino-Americana; BrasilFil: Rose, Miranda Brooke. University of California; Estados UnidosFil: de Andrade, AndrĂ© Felipe Alves. Universidade Federal de GoiĂĄs; BrasilFil: Minoli, Ignacio. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Nordeste. Instituto de BiologĂ­a Subtropical. Instituto de BiologĂ­a Subtropical - Nodo Puerto IguazĂș | Universidad Nacional de Misiones. Instituto de BiologĂ­a Subtropical. Instituto de BiologĂ­a Subtropical - Nodo Puerto IguazĂș; ArgentinaFil: Franklin, Janet. University of California; Estados Unido

    Impact of uric acid on liver injury and intestinal permeability following resuscitated hemorrhagic shock in rats

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    BACKGROUND Multiorgan failure is a consequence of severe ischemia-reperfusion injury after traumatic hemorrhagic shock (HS), a major cause of mortality in trauma patients. Circulating uric acid (UA), released from cell lysis, is known to activate proinflammatory and proapoptotic pathways and has been associated with poor clinical outcomes among critically ill patients. Our group has recently shown a mediator role for UA in kidney and lung injury, but its role in liver and enteric damage after HS remains undefined. Therefore, the objective of this study was to evaluate the role of UA on liver and enteric injury after resuscitated HS. METHODS A murine model of resuscitated HS was treated during resuscitation with a recombinant uricase, a urate oxidase enzyme (rasburicase; Sanofi-Aventis, Canada Inc, Laval, Canada), to metabolize and reduce circulating UA. Biochemical analyses (liver enzymes, liver apoptotic, and inflammatory markers) were performed at 24 hours and 72 hours after HS. Physiological testing for enteric permeability and gut bacterial product translocation measurement (plasma endotoxin) were performed 72 hours after HS. In vitro, HT-29 cells were exposed to UA, and the expression of intercellular adhesion proteins (ZO-1, E-cadherin) was measured to evaluate the influence of UA on enteric permeability. RESULTS The addition of uricase to resuscitation significantly reduced circulating and liver UA levels after HS. It also prevented HS-induced hepatolysis and liver apoptotic/inflammatory mediators at 24 hours and 72 hours. Hemorrhagic shock–induced enteric hyperpermeability and endotoxemia were prevented with uricase. CONCLUSIONS After resuscitated HS, UA is an important mediator in liver and enteric injury. Uric acid represents a therapeutic target to minimize organ damage in polytrauma patients sustaining HS

    Mid infrared near-field fingerprint spectroscopy of the 2D electron gas in LaAlO3_3/SrTiO3_3 at low temperatures

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    Confined electron systems, such as 2D electron gases (2DEGs), 2D materials, or topological insulators show great technological promise but their susceptibility to defects often results in nanoscale inhomogeneities with unclear origins. Scattering-type scanning near-field optical microscopy (s-SNOM) is useful to investigate buried confined electron systems non-destructively with nanoscale resolution, however, a clear separation of carrier concentration and mobility was often impossible in s-SNOM. Here, we predict a previously inaccessible characteristic "fingerprint" response of the prototypical LaAlO3_3/SrTiO3_3 2DEG, and verify this using a state-of-the-art tunable narrow-band laser in mid-infrared cryo-s-SNOM at 8 K. Our modelling allows us to separate the influence of carrier concentration and mobility on fingerprint spectra and to characterize 2DEG inhomogeneities on the nanoscale. This spatially resolved information about the local electronic properties can be used to identify the origin of inhomogeneities in confined electron systems, making the s-SNOM fingerprint response a valuable tool for nanoelectronics and quantum technology

    Development and validation of risk-adjusted quality indicators for the long-term outcome of acute sepsis care in German hospitals based on health claims data

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    Background Methods for assessing long-term outcome quality of acute care for sepsis are lacking. We investigated a method for measuring long-term outcome quality based on health claims data in Germany. Materials and methods Analyses were based on data of the largest German health insurer, covering 32% of the population. Cases (aged 15 years and older) with ICD-10-codes for severe sepsis or septic shock according to sepsis-1-definitions hospitalized in 2014 were included. Short-term outcome was assessed by 90-day mortality; long-term outcome was assessed by a composite endpoint defined by 1-year mortality or increased dependency on chronic care. Risk factors were identified by logistic regressions with backward selection. Hierarchical generalized linear models were used to correct for clustering of cases in hospitals. Predictive validity of the models was assessed by internal validation using bootstrap-sampling. Risk-standardized mortality rates (RSMR) were calculated with and without reliability adjustment and their univariate and bivariate distributions were described. Results Among 35,552 included patients, 53.2% died within 90 days after admission; 39.8% of 90-day survivors died within the first year or had an increased dependency on chronic care. Both risk-models showed a sufficient predictive validity regarding discrimination [ AUC = 0.748 (95% CI: 0.742; 0.752) for 90-day mortality; AUC = 0.675 (95% CI: 0.665; 0.685) for the 1-year composite outcome, respectively], calibration (Brier Score of 0.203 and 0.220; calibration slope of 1.094 and 0.978), and explained variance ( R 2 = 0.242 and R 2 = 0.111). Because of a small case-volume per hospital, applying reliability adjustment to the RSMR led to a great decrease in variability across hospitals [from median (1st quartile, 3rd quartile) 54.2% (44.3%, 65.5%) to 53.2% (50.7%, 55.9%) for 90-day mortality; from 39.2% (27.8%, 51.1%) to 39.9% (39.5%, 40.4%) for the 1-year composite endpoint]. There was no substantial correlation between the two endpoints at hospital level (observed rates: ρ = 0, p = 0.99; RSMR: ρ = 0.017, p = 0.56; reliability-adjusted RSMR: ρ = 0.067; p = 0.026). Conclusion Quality assurance and epidemiological surveillance of sepsis care should include indicators of long-term mortality and morbidity. Claims-based risk-adjustment models for quality indicators of acute sepsis care showed satisfactory predictive validity. To increase reliability of measurement, data sources should cover the full population and hospitals need to improve ICD-10-coding of sepsis
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