Iron Sucrose: A Wealth of Experience in Treating Iron Deficiency

Iron deficiency and iron-deficiency anemia are associated with increased morbidity and mortality in a wide range of conditions. In many patient populations, this can be treated effectively with oral iron supplementation; but in patients who are unable to take or who do not respond to oral iron therapy, intravenous iron administration is recommended. Furthermore, in certain conditions, such as end-stage kidney disease, chronic heart failure, and inflammatory bowel disease, intravenous iron administration has become first-line treatment. One of the first available intravenous iron preparations is iron sucrose (Venofer®), a nanomedicine that has been used clinically since 1949. Treatment with iron sucrose is particularly beneficial owing to its ability to rapidly increase hemoglobin, ferritin, and transferrin saturation levels, with an acceptable safety profile. Recently, important new data relating to the use of iron sucrose, including the findings from the landmark PIVOTAL trial in patients with end-stage kidney disease, have been reported. Several years ago, a number of iron sucrose similars became available, although there have been concerns about the clinical appropriateness of substituting the original iron sucrose with an iron sucrose similar because of differences in efficacy and safety. This is a result of the complex and unique physicochemical properties of nanomedicines such as iron sucrose, which make copying the molecule difficult and problematic. In this review, we summarize the evidence accumulated during 70 years of clinical experience with iron sucrose in terms of efficacy, safety, and cost-effectiveness

Traumatic brain injury leads to alterations in contusional cortical miRNAs involved in dementia

There is compelling evidence that head injury is a significant environmental risk factor for Alzheimer's disease (AD) and that a history of traumatic brain injury (TBI) accelerates the onset of AD. Amyloid-β plaques and tau aggregates have been observed in the post-mortem brains of TBI patients; however, the mechanisms leading to AD neuropathology in TBI are still unknown. In this study, we hypothesized that focal TBI induces changes in miRNA expression in and around affected areas, resulting in the altered expression of genes involved in neurodegeneration and AD pathology. For this purpose, we performed a miRNA array in extracts from rats subjected to experimental TBI, using the controlled cortical impact (CCI) model. In and around the contusion, we observed alterations of miRNAs associated with dementia/AD, compared to the contralateral side. Specifically, the expression of miR-9 was significantly upregulated, while miR-29b, miR-34a, miR-106b, miR-181a and miR-107 were downregulated. Via qPCR, we confirmed these results in an additional group of injured rats when compared to naïve animals. Interestingly, the changes in those miRNAs were concomitant with alterations in the gene expression of mRNAs involved in amyloid generation and tau pathology, such as β-APP cleaving enzyme (BACE1) and Glycogen synthase-3-β (GSK3β). In addition increased levels of neuroinflammatory markers (TNF-α), glial activation, neuronal loss, and tau phosphorylation were observed in pericontusional areas. Therefore, our results suggest that the secondary injury cascade in TBI affects miRNAs regulating the expression of genes involved in AD dementia

Three Dimensional Numerical General Relativistic Hydrodynamics I: Formulations, Methods, and Code Tests

This is the first in a series of papers on the construction and validation of a three-dimensional code for general relativistic hydrodynamics, and its application to general relativistic astrophysics. This paper studies the consistency and convergence of our general relativistic hydrodynamic treatment and its coupling to the spacetime evolutions described by the full set of Einstein equations with a perfect fluid source. The numerical treatment of the general relativistic hydrodynamic equations is based on high resolution shock capturing schemes. These schemes rely on the characteristic information of the system. A spectral decomposition for general relativistic hydrodynamics suitable for a general spacetime metric is presented. Evolutions based on three different approximate Riemann solvers coupled to four different discretizations of the Einstein equations are studied and compared. The coupling between the hydrodynamics and the spacetime (the right and left hand side of the Einstein equations) is carried out in a treatment which is second order accurate in {\it both} space and time. Convergence tests for all twelve combinations with a variety of test beds are studied, showing consistency with the differential equations and correct convergence properties. The test-beds examined include shocktubes, Friedmann-Robertson-Walker cosmology tests, evolutions of self-gravitating compact (TOV) stars, and evolutions of relativistically boosted TOV stars. Special attention is paid to the numerical evolution of strongly gravitating objects, e.g., neutron stars, in the full theory of general relativity, including a simple, yet effective treatment for the surface region of the star (where the rest mass density is abruptly dropping to zero).Comment: 45 pages RevTeX, 34 figure

Relativistic hydrodynamics on spacelike and null surfaces: Formalism and computations of spherically symmetric spacetimes

We introduce a formulation of Eulerian general relativistic hydrodynamics which is applicable for (perfect) fluid data prescribed on either spacelike or null hypersurfaces. Simple explicit expressions for the characteristic speeds and fields are derived in the general case. A complete implementation of the formalism is developed in the case of spherical symmetry. The algorithm is tested in a number of different situations, predisposing for a range of possible applications. We consider the Riemann problem for a polytropic gas, with initial data given on a retarded/advanced time slice of Minkowski spacetime. We compute perfect fluid accretion onto a Schwarzschild black hole spacetime using ingoing null Eddington-Finkelstein coordinates. Tests of fluid evolution on dynamic background include constant density and TOV stars sliced along the radial null cones. Finally, we consider the accretion of self-gravitating matter onto a central black hole and the ensuing increase in the mass of the black hole horizon.Comment: 23 pages, 13 figures, submitted to Phys. Rev.

Anesthesia personnel’s visual attention regarding patient monitoring in simulated non-critical and critical situations, an eye-tracking study

Background: Cognitive ergonomics design of patient monitoring may reduce human factor errors in high-stress environments. Eye-tracking is a suitable tool to gain insight into the distribution of visual attention of healthcare professionals with patient monitors, which may facilitate their further development. Methods: This prospective, exploratory, high-fidelity simulation study compared anesthesia personnel's visual attention (fixation count and dwell-time) to 15 areas of interest on the patient monitor during non-critical and critical anesthesia situations. Furthermore, we examined the extent to which participants' experience influenced visual attention and which vital signs displayed on the patient monitor received the most visual attention. We used mixed zero-inflated Poisson regression and mixed linear models to analyze the data. Results: Analyzing 23 ten-minute scenarios, we found significantly more fixations to the areas of interest on the patient monitor during critical than non-critical situations (rate ratio of 1.45; 95% CI 1.33 to 1.59; p < 0.001). However, the dwell-time on the areas of interest did not significantly differ between the non-critical and critical situations (coefficient of - 1.667; 95% CI - 4.549 to 1.229; p = 0.27). The professional experience did not significantly influence the visual attention (fixation: rate ratio of 0.88; 95% CI 0.54 to 1.43; p = 0.61 and dwell-time: coefficient of 0.889; 95% CI - 1.465 to 3.229; p = 0.27). Over all situations, anesthesia personnel paid the most attention to the vital signs blood pressure (fixation: mean [SD] of 108 [74.83]; dwell-time: mean [SD] of 27 [15.90] seconds), end-expiratory carbon dioxide (fixation: mean [SD] of 59 [47.39]; dwell-time: mean [SD] of 30 [21.51] seconds), and the electrocardiogram (fixation: mean [SD] of 58 [64.70]; dwell-time: mean [SD] of 15 [14.95] seconds). Conclusions: Critical anesthesia situations increased anesthesia personnel's visual interaction with the patient monitor. Furthermore, we found that their visual attention focused mainly on a few vital signs. To assist clinicians in critical situations, manufacturers should optimize monitors to convey necessary information as easily and quickly as possible and optimize the visibility of less frequently observed but equally critical vital signs, especially when they are in an abnormal range. Keywords: Anesthesia, general; Eye-tracking technology; Patient monitoring; Patient simulation; Situation awareness; Visual attention

Correction to: The intake of flavonoids, stilbenes, and tyrosols, mainly consumed through red wine and virgin olive oil, is associated with lower carotid and femoral subclinical atherosclerosis and coronary calcium

The original version of this article unfortunately contained a mistake. The author’s name Henry Montero-Salazar was incorrectly written as Henry Montero Salazar. © The Author(s) 2022

Relativistic Hydrodynamics around Black Holes and Horizon Adapted Coordinate Systems

Despite the fact that the Schwarzschild and Kerr solutions for the Einstein equations, when written in standard Schwarzschild and Boyer-Lindquist coordinates, present coordinate singularities, all numerical studies of accretion flows onto collapsed objects have been widely using them over the years. This approach introduces conceptual and practical complications in places where a smooth solution should be guaranteed, i.e., at the gravitational radius. In the present paper, we propose an alternative way of solving the general relativistic hydrodynamic equations in background (fixed) black hole spacetimes. We identify classes of coordinates in which the (possibly rotating) black hole metric is free of coordinate singularities at the horizon, independent of time, and admits a spacelike decomposition. In the spherically symmetric, non-rotating case, we re-derive exact solutions for dust and perfect fluid accretion in Eddington-Finkelstein coordinates, and compare with numerical hydrodynamic integrations. We perform representative axisymmetric computations. These demonstrations suggest that the use of those coordinate systems carries significant improvements over the standard approach, especially for higher dimensional studies.Comment: 10 pages, 4 postscript figures, accepted for publication in Phys. Rev.

Determinantal Characterization of Canonical Curves and Combinatorial Theta Identities

We characterize genus g canonical curves by the vanishing of combinatorial products of g+1 determinants of Brill-Noether matrices. This also implies the characterization of canonical curves in terms of (g-2)(g-3)/2 theta identities. A remarkable mechanism, based on a basis of H^0(K_C) expressed in terms of Szego kernels, reduces such identities to a simple rank condition for matrices whose entries are logarithmic derivatives of theta functions. Such a basis, together with the Fay trisecant identity, also leads to the solution of the question of expressing the determinant of Brill-Noether matrices in terms of theta functions, without using the problematic Klein-Fay section sigma.Comment: 35 pages. New results, presentation improved, clarifications added. Accepted for publication in Math. An

Numerical simulation of small perturbation on an accretion disk due to the collision of a star with the disk near the black hole

In this paper, perturbations of an accretion disk by a star orbiting around a black hole are studied. We report on a numerical experiment, which has been carried out by using a parallel-machine code originally developed by D\"{o}nmez (2004). An initially steady state accretion disk near a non-rotating (Schwarzschild) black hole interacts with a "star", modeled as an initially circular region of increased density. Part of the disk is affected by the interaction. In some cases, a gap develops and shock wave propagates through the disk. We follow the evolution for order of one dynamical period and we show how the non-axisymetric density perturbation further evolves and moves downwards where the material of the disk and the star become eventually accreted onto the central body. When the star perturbs the steady state accretion disk, the disk around the black hole is destroyed by the effect of perturbation. The perturbed accretion disk creates a shock wave during the evolution and it loses angular momentum when the gas hits on the shock waves. Colliding gas with the shock wave is the one of the basic mechanism of emitting the $X-$rays in the accretion disk. The series of supernovae occurring in the inner disk could entirely destroy the disk in that region which leaves a more massive black hole behind, at the center of galaxies.Comment: 20pages, 8 figures, accepted for publication in Astrophysics and Space Scienc

Reassessing changes in diurnal temperature range: Intercomparison and evaluation of existing global data set estimates

Changes in diurnal temperature range (DTR) over global land areas are compared from a broad range of independent data sets. All data sets agree that global-mean DTR has decreased significantly since 1950, with most of that decrease occurring over 1960–1980. The since-1979 trends are not significant, with inter-data set disagreement even over the sign of global changes. Inter-data set spread becomes greater regionally and in particular at the grid box level. Despite this, there is general agreement that DTR decreased in North America, Europe, and Australia since 1951, with this decrease being partially reversed over Australia and Europe since the early 1980s. There is substantive disagreement between data sets prior to the middle of the twentieth century, particularly over Europe, which precludes making any meaningful conclusions about DTR changes prior to 1950, either globally or regionally. Several variants that undertake a broad range of approaches to postprocessing steps of gridding and interpolation were analyzed for two of the data sets. These choices have a substantial influence in data sparse regions or periods. The potential of further insights is therefore inextricably linked with the efficacy of data rescue and digitization for maximum and minimum temperature series prior to 1950 everywhere and in data sparse regions throughout the period of record. Over North America, station selection and homogeneity assessment is the primary determinant. Over Europe, where the basic station data are similar, the postprocessing choices are dominant. We assess that globally averaged DTR has decreased since the middle twentieth century but that this decrease has not been linear