Epidermal mineralocorticoid receptor plays beneficial and adverse effects in skin and mediates glucocorticoid responses

10 páginas, 6 figuras. Contiene material suplementarioGlucocorticoids (GCs) regulate skin homeostasis and combat cutaneous inflammatory diseases; however, adverse effects of chronic GC treatments limit their therapeutic use. GCs bind and activate the GC receptor and the mineralocorticoid receptor (MR), transcription factors that recognize identical hormone responsive elements. Whether epidermal MR mediates beneficial or deleterious GC effects is of great interest for improving GC-based skin therapies. MR epidermal knockout mice exhibited increased keratinocyte proliferation and differentiation and showed resistance to GC-induced epidermal thinning. However, crucially, loss of epidermal MR rendered mice more sensitive to inflammatory stimuli and skin damage. MR epidermal knockout mice showed increased susceptibility to phorbol 12-myristate 13-acetate-induced inflammation with higher cytokine induction. Likewise, cultured MR epidermal knockout keratinocytes had increased phorbol 12-myristate 13-acetate-induced NF-κB activation, highlighting an anti-inflammatory function for MR. GC-induced transcription was reduced in MR epidermal knockout keratinocytes, at least partially due to decreased recruitment of GC receptor to hormone responsive element-containing sequences. Our results support a role for epidermal MR in adult skin homeostasis and demonstrate nonredundant roles for MR and GC receptor in mediating GC actions.This work was supported by grant SAF2011-28115 and SAF2014-59474-R (MINECO, Spanish Government). JB and EC are recipients of FPI (BES-2012-0578) and FPU (AP201-06094) fellowships of MINECO, respectively. We thank COST ADMIRE BM- 1301 and NURCAMEIN (SAF2015-71878-REDT) for support for dissemination.Peer reviewe

Analyzing the Effects of Body Mass Index in Total Hip Arthroplasty Cases. Does it Influence Patient Characteristics, Operative Planning, and Postoperative Outcomes?

Background: Total hip arthroplasty (THA) is one of the most performed orthopaedic procedures commonly used for the treatment of osteoarthritis (OA). There are several underlying factors that lead to the formation of this condition. Not only is obesity one of the main contributors, but it is also a modifiable risk factor and one of the leading causes of end-stage arthrosis of the hip. Though there have been advancements in agricultural and health technologies, rates of obesity continue to rise causing similar increases in the demands for hip replacement surgeries. Therefore, we sought to investigate the effects of BMI on THA procedures and determine if it plays any influential role in patient characteristics, operative planning, and postoperative outcomes. Methods: A prospectively collected database from a single institution was queried from January 2018 to December 2021, to identify 66 THA patients (mean age 69.5) included in this study. Patient’s BMI were recorded preoperatively and separated into five classes in accordance with the World Health Organization classification of Normal (18.5-24.9), Pre-Obesity (25.0-29.9), Obesity Class I (30.0-34.9), Obesity Class II (35.0-39.9), and Obesity Class III (BMI ≥ 40). Patient attributes, operative characteristics, and postoperative outcomes were then stratified and grouped into the different BMI classes. All patients had radiograph imaging obtained preoperatively and at a minimum 9-month interval to observe for the presence of any radiolucent lines which would be plotted using the hip regions set forth by De Lee and Charnley. Results: The mean BMI of our patient population was 30.5 which overall characterizes it as Obesity Class I. However, the classification that contained the most of our population was Pre-Obesity (n = 26, 39.4%). There were no males in our entire population that had a BMI considered normal, but 13 females did fall into this classification. There was a significant number of patients who underwent a direct anterior approach within the Pre-Obesity classification than those who underwent a posterolateral approach (21 vs 5 patients, P value = 0.047). However, for subjects meeting Obesity Class II and Class III criteria, a significant number of posterolateral approaches were performed than the direct anterior approach. In analyzing the radiographs, only 2 patients were discovered to have radiolucent lines, but no related symptoms or physical complications were reported. Conclusion: Our investigation demonstrates that having a higher BMI only significantly affects the surgical approach to THA but can conclude that it is an excellent surgical option for the treatment of OA in obese patients

The mineralocorticoid receptor plays a transient role in mouse skin development

3 páginas, 2 figuras. Contiene material suplemenarioGlucocorticoid (GC) hormones can bind two structurally and functionally related steroid receptors: the GC Receptor (GR or Nr3c1) and the mineralocorticoid receptor (MR or Nr3c2), which recognize the same DNA response elements and act as ligand-dependent transcription factors. While the crucial role of GR for skin homeostasis has been widely characterized, the exact role of MR in this tissue deserves further study. We assessed NR3C2 expression in developing and adult WT mouse skin and found a transient peak at embryonic day (E)16.5, which along with low levels of HSD11B2, the enzyme inactivating GCs, supports a role for GC-MR complexes in epidermal maturation. Consistent with this observation, MR-/- embryonic skin showed alterations in early epidermal differentiation that resolved postnatally. The lack of a more severe skin phenotype of MR-/- mice suggests functional compensation by GR in this tissue in the perinatal period.This work was supported by JSPS KAKENHI grant numbers 25870545 and 15K09772. Spanish Ministerio de Ciencia e Innovación. Grant Numbers: SAF2011-28115, SAF2014-59474-RPeer Reviewe

Kinetics of the invasion and egress processes of Babesia divergens, observed by time-lapse video microscopy

Based on confocal fluorescence and bright field video microscopy, we present detailed observations on the processes of invasion and egress of erythrocytes by the apicomplexan parasite Babesia divergens. Time-lapse images reveal numerous unexpected findings associated with the dynamics of B. divergens and its ability to manipulate the erythrocyte during both processes in its asexual cycle under in vitro conditions. Despite the speed at which these processes occur and the small size of the parasite, we capture infective merozoites moving vigorously and causing striking deformations in the erythrocyte's plasma membrane during an active invasion. We also observed intraerythrocytic dynamic stages as paired pyriforms, double paired pyriforms, tetrads, unattached pyriform sister cells and multiple parasite stages resulting in the release of large numbers of merozoites over a short period. Of considerable interest is that time-lapse images reveal a novel mechanism of egress used by B. divergens to exit the human erythrocyte. The release occurs when B. divergens parasites establish contacts with the plasma membrane of the erythrocyte from within, before exiting the cell. Visualization and analysis of the images enabled us to obtain useful information and broaden our knowledge of complex and crucial events involved with parasitisation of human erythrocytes by B. divergens.This work was funded by grants from Ministerio de Economía y Competitividad from Spain (AGL2010-21774, AGL2014-56193 R to EM and LMG). E. Sevilla was awarded a research fellowship from Plan Estatal de Investigación Científica y Técnica y de Innovación, Ministerio de Economía y Competitividad, Spain.S

A simple formula for the computation of branches and asymptotes of curves and some applications

In this paper, we obtain a simple formula based on the computation of some derivatives for determining the branches and the asymptotes of curves that are defined by a parametrization. For this purpose, we use some previous results and notions presented in Blasco and Pérez-Díaz, 2014a, Blasco and Pérez-Díaz, 2014b, Blasco and Pérez-Díaz, 2015, Blasco and Pérez-Díaz, 2020. From these results, we show how the generalized asymptotes of the input curve can be easily computed and we present some applications related to the ramification index and degree of the asymptote, the infinity form and the multiplicity of the infinity points. Furthermore, we show how to construct all the families of parametric curves having some given asymptotes. We develop this method for the plane case but it can be trivially adapted for dealing with rational curves in n-dimensional space. In addition, the formulaes presented can be similarly obtained for curves defined by a parametrization not necessarily rational.Agencia Estatal de Investigació

Asymptotic behavior of a surface implicitly defined

In this paper, we introduce the notion of infinity branches and approaching surfaces. We obtain an algorithm that compares the behavior at the infinity of two given algebraic surfaces that are defined by an irreducible polynomial. Furthermore, we show that if two surfaces have the same asymptotic behavior, the Hausdorff distance between them is finite. All these concepts are new and represent a great advance for the study of surfaces and their applications.Agencia Estatal de Investigació

Chemotactic response of the flavonoid daidzein and its effect on the composition of the rumen bacterial community

Daidzein is one of common metabolites in plants and has chemotactic effect on soil bacteria that colonize the plants. There are several tests to assess bacterial chemotaxis, but none focused on rumen bacteria. Therefore, the aim of this study was to test the chemotactic response of the rumen microflora towards daidzein using a standardized bacterial chemotaxis assay. It consisted in a modifying capillary technique and employing technology for measuring in vitro gas production. Ruminal fluids and cellulose were used as controls. The response of bacteria to daidzein was greater than the response to cellulose, supporting the hypothesis that when fodder is chewed by the ruminant it releases daidzein which can attract rumen bacteria towards feed particles (chemotaxis) for attachment and subsequent degradation

Determining the asymptotic family of an implicit curve

In this paper we deal with the following problem: given an algebraic plane curve C, implicitly defined, we determine its “asymptotic family”, that is, the set of algebraic curves that have the same asymptotic behavior as C.Agencia Estatal de Investigació

Some New Symbolic Algorithms for the Computation of Generalized Asymptotes

We present symbolic algorithms for computing the g-asymptotes, or generalized asymptotes, of a plane algebraic curve, C, implicitly or parametrically defined. The g-asymptotes generalize the classical concept of asymptotes of a plane algebraic curve. Both notions have been previously studied for analyzing the geometry and topology of a curve at infinity points, as well as to detect the symmetries that can occur in coordinates far from the origin. Thus, based on this research, and in order to solve practical problems in the fields of science and engineering, we present the pseudocodes and implementations of algorithms based on the Puiseux series expansion to construct the g-asymptotes of a plane algebraic curve, implicitly or parametrically defined. Additionally, we propose some new symbolic methods and their corresponding implementations which improve the efficiency of the preceding. These new methods are based on the computation of limits and derivatives; they show higher computational performance, demanding fewer hardware resources and system requirements, as well as reducing computer overload. Finally, as a novelty in this research area, a comparative analysis for all the algorithms is carried out, considering the properties of the input curves and their outcomes, to analyze their efficiency and to establish comparative criteria between them.Agencia Estatal de Investigació

Groupwise Non-Rigid Registration with Deep Learning: An Affordable Solution Applied to 2D Cardiac Cine MRI Reconstruction

Groupwise image (GW) registration is customarily used for subsequent processing in medical imaging. However, it is computationally expensive due to repeated calculation of transformations and gradients. In this paper, we propose a deep learning (DL) architecture that achieves GW elastic registration of a 2D dynamic sequence on an affordable average GPU. Our solution, referred to as dGW, is a simplified version of the well-known U-net. In our GW solution, the image that the other images are registered to, referred to in the paper as template image, is iteratively obtained together with the registered images. Design and evaluation have been carried out using 2D cine cardiac MR slices from 2 databases respectively consisting of 89 and 41 subjects. The first database was used for training and validation with 66.6–33.3% split. The second one was used for validation (50%) and testing (50%). Additional network hyperparameters, which are—in essence—those that control the transformation smoothness degree, are obtained by means of a forward selection procedure. Our results show a 9-fold runtime reduction with respect to an optimization-based implementation; in addition, making use of the well-known structural similarity (SSIM) index we have obtained significative differences with dGW with respect to an alternative DL solution based on Voxelmorph