Effects of Progesterone and Its Antagonist Mifepristone on Progesterone Receptor A Expression in Human Umbilical Vein Endothelial Cells

Effects of female steroid hormones on endothelial cells are gaining increased importance due to several studies on the effects of hormonal treatment on cardiovascular risk. Recent data argue for an improvement of endothelium-derived relaxation and impaired vascular contraction by estradiol, whereas progesterone and testosterone might entail contrary effects. So far, gestagenic influence on endothelial cell physiology is poorly understood. Human umbilical vein endothelial cells (HUVECs) exposed to the female sex hormones estradiol and progesterone show expression of estrogen receptor-beta (ER beta) and progesterone receptor A (PR-A), and are negative for ER alpha and PR-B. The aim of this study was to analyze the expression and stimulation of PR-A and -B in HUVECs after stimulation with progesterone and PR antagonists that are commercially available. PR-B expression or upregulation was abrogated after application of progesterone or antagonists to HUVECs. Expression of PR-A could be significantly upregulated with progesterone and mifepristone. Unexpectedly, stimulation with the progesterone antagonist RU486 (mifepristone) was accomplished by an upregulation of PR-A expression in our study. We conclude that gestagenic effects on HUVECs independent of modulators are mediated via the PR-A. Copyright (C) 2009 S. Karger AG, Base

Long-Term Persistance of the Pathophysiologic Response to Severe Burn Injury

Main contributors to adverse outcomes in severely burned pediatric patients are profound and complex metabolic changes in response to the initial injury. It is currently unknown how long these conditions persist beyond the acute phase post-injury. The aim of the present study was to examine the persistence of abnormalities of various clinical parameters commonly utilized to assess the degree hypermetabolic and inflammatory alterations in severely burned children for up to three years post-burn to identify patient specific therapeutic needs and interventions. Nine-hundred seventy-seven severely burned pediatric patients with burns over 30% of the total body surface admitted to our institution between 1998 and 2008 were enrolled in this study and compared to a cohort non-burned, non-injured children. Demographics and clinical outcomes, hypermetabolism, body composition, organ function, inflammatory and acute phase responses were determined at admission and subsequent regular intervals for up to 36 months post-burn. Statistical analysis was performed using One-way ANOVA, Student's t-test with Bonferroni correction where appropriate with significance accepted at p<0.05. Resting energy expenditure, body composition, metabolic markers, cardiac and organ function clearly demonstrated that burn caused profound alterations for up to three years post-burn demonstrating marked and prolonged hypermetabolism, p<0.05. Along with increased hypermetabolism, significant elevation of cortisol, catecholamines, cytokines, and acute phase proteins indicate that burn patients are in a hyperinflammatory state for up to three years post-burn p<0.05. Severe burn injury leads to a much more profound and prolonged hypermetabolic and hyperinflammatory response than previously shown. Given the tremendous adverse events associated with the hypermetabolic and hyperinflamamtory responses, we now identified treatment needs for severely burned patients for a much more prolonged time

Similarities between structural distortions under pressure and chemical doping in superconducting BaFe2As2

The discovery of a new family of high Tc materials, the iron arsenides (FeAs), has led to a resurgence of interest in superconductivity. Several important traits of these materials are now apparent, for example, layers of iron tetrahedrally coordinated by arsenic are crucial structural ingredients. It is also now well established that the parent non-superconducting phases are itinerant magnets, and that superconductivity can be induced by either chemical substitution or application of pressure, in sharp contrast to the cuprate family of materials. The structure and properties of chemically substituted samples are known to be intimately linked, however, remarkably little is known about this relationship when high pressure is used to induce superconductivity in undoped compounds. Here we show that the key structural features in BaFe2As2, namely suppression of the tetragonal to orthorhombic phase transition and reduction in the As-Fe-As bond angle and Fe-Fe distance, show the same behavior under pressure as found in chemically substituted samples. Using experimentally derived structural data, we show that the electronic structure evolves similarly in both cases. These results suggest that modification of the Fermi surface by structural distortions is more important than charge doping for inducing superconductivity in BaFe2As2

Dynamic and thermodynamic properties of the generalised diamond chain model for azurite

The natural mineral azurite Cu3(CO3)2(OH)2 is an interesting spin-1/2 quantum antiferromagnet. Recently, a generalised diamond chain model has been established as a good description of the magnetic properties of azurite with parameters placing it in a highly frustrated parameter regime. Here we explore further properties of this model for azurite. First, we determine the inelastic neutron scattering spectrum in the absence of a magnetic field and find good agreement with experiments, thus lending further support to the model. Furthermore, we present numerical data for the magnetocaloric effect and predict that strong cooling should be observed during adiabatic (de)magnetisation of azurite in magnetic fields slightly above 30T. Finally, the presence of a dominant dimer interaction in azurite suggests the use of effective Hamiltonians for an effective low-energy description and we propose that such an approach may be useful to fully account for the three-dimensional coupling geometry.Comment: 19 pages, 6 figures; to appear in: J. Phys.: Condens. Matter (special issue on geometrically frustrated magnetism

"Extraordinary" Phase Transition Revealed in a van der Waals Antiferromagnet

While the surface-bulk correspondence has been ubiquitously shown in topological phases, the relationship between surface and bulk in Landau-like phases is much less explored. Theoretical investigations since 1970s for semi-infinite systems have predicted the possibility of the surface order emerging at a higher temperature than the bulk, clearly illustrating a counterintuitive situation and greatly enriching phase transitions. But experimental realizations of this prediction remain missing. Here, we demonstrate the higher-temperature surface and lower-temperature bulk phase transitions in CrSBr, a van der Waals (vdW) layered antiferromagnet. We leverage the surface sensitivity of electric dipole second harmonic generation (SHG) to resolve surface magnetism, the bulk nature of electric quadrupole SHG to probe bulk spin correlations, and their interference to capture the two magnetic domain states. Our density functional theory calculations show the suppression of ferromagnetic-antiferromagnetic competition at the surface responsible for this enhanced surface magnetism. Our results not only show unexpected, richer phase transitions in vdW magnets, but also provide viable ways to enhance magnetism in their 2D form

Using ordinal logistic regression to evaluate the performance of laser-Doppler predictions of burn-healing time

Background Laser-Doppler imaging (LDI) of cutaneous blood flow is beginning to be used by burn surgeons to predict the healing time of burn wounds; predicted healing time is used to determine wound treatment as either dressings or surgery. In this paper, we do a statistical analysis of the performance of the technique. Methods We used data from a study carried out by five burn centers: LDI was done once between days 2 to 5 post burn, and healing was assessed at both 14 days and 21 days post burn. Random-effects ordinal logistic regression and other models such as the continuation ratio model were used to model healing-time as a function of the LDI data, and of demographic and wound history variables. Statistical methods were also used to study the false-color palette, which enables the laser-Doppler imager to be used by clinicians as a decision-support tool. Results Overall performance is that diagnoses are over 90% correct. Related questions addressed were what was the best blood flow summary statistic and whether, given the blood flow measurements, demographic and observational variables had any additional predictive power (age, sex, race, % total body surface area burned (%TBSA), site and cause of burn, day of LDI scan, burn center). It was found that mean laser-Doppler flux over a wound area was the best statistic, and that, given the same mean flux, women recover slightly more slowly than men. Further, the likely degradation in predictive performance on moving to a patient group with larger %TBSA than those in the data sample was studied, and shown to be small. Conclusion Modeling healing time is a complex statistical problem, with random effects due to multiple burn areas per individual, and censoring caused by patients missing hospital visits and undergoing surgery. This analysis applies state-of-the art statistical methods such as the bootstrap and permutation tests to a medical problem of topical interest. New medical findings are that age and %TBSA are not important predictors of healing time when the LDI results are known, whereas gender does influence recovery time, even when blood flow is controlled for. The conclusion regarding the palette is that an optimum three-color palette can be chosen 'automatically', but the optimum choice of a 5-color palette cannot be made solely by optimizing the percentage of correct diagnoses

Multi-step approach to microscopic models for frustrated quantum magnets - the case of the natural mineral azurite

The natural mineral azurite Cu$_3$(CO$_3$)$_2$(OH)$_2$ is a frustrated magnet displaying unusual and controversially discussed magnetic behavior. Motivated by the lack of a unified description for this system, we perform a theoretical study based on density functional theory as well as state-of-the-art numerical many-body calculations. We propose an effective generalized spin-1/2 diamond chain model which provides a consistent description of experiments: low-temperature magnetization, inelastic neutron scattering, nuclear magnetic resonance measurements, magnetic susceptibility as well as new specific heat measurements. With this study we demonstrate that the balanced combination of first principles with powerful many-body methods successfully describes the behavior of this frustrated material.Comment: final version to appear in Phys. Rev. Lett.; 10 pages, 9 figures, 4 tables (including supplementary material