Hipersensibilidad en el gato

En el gato, el picor es un signo más difícil de reconocer que en el perro. Las manifestaciones clínicas de prurito son muy limitadas en la especie felina, de tal forma que se pueden reducir a cinco formas o cuadros principales:(1)la dermatitis miliar,(2)el prurito facial, (3) la alopecia simétrica, (4) el complejo granuloma eosinofílico y (5) la dermatitis costrosa/escamosa más o menos localizada. De entre las numerosas causas que pueden ocasionar picores, las reacciones de hipersensibilidad (a pulgas, alimentos, alérgenos inhalados, alérgenos de contacto, fármacos y parásitos intestinales) constituyen el grupo etiológico más importante después de los procesos parasitarios. Debido a la similitud de sintomatología cutánea que manifiestan los distintos alérgenos, se impone un buen conocimiento de los tests laboraroriales disponibles de cara a establecer un diagnóstico diferencial preciso y un tratamiento idóneo.The itchy in the cat is more difficult to recognize than the itchy in the dog. There are only five important patterns of cutaneous disease associated with pruritus in the cat: (1) miliary dermatitis, (2) pruritus of the head, (3) symetrical alopecia, (4) eosinophilic granuloma complex, and (5) regional or generalized scaling/crusting dermatosis. Hipersensibility (to flea, aereoalergen, food, contac, drug, intestinal parasite) is after parasitic dermatosis, the most important cause of pruritus. Because the simzJarcutaneous manzfestation of the different alergens, is neccessary to know the laboratory tests in arder to stablishing an accurate diagnosis and the better treatment

Characterization, conservation and loss of dignity at the end-of- life in the emergency department. A qualitative protocol

Aims: to explore and understand the experiences of terminally-ill patients and their relatives regarding dignity during end-of-life care in the emergency department. Background: the respect given to the concept of dignity is significantly modifying the clinical relationship and the care framework involving the end-of-life patient in palliative care units, critical care units, hospices and their own homes. This situation is applicable to in-hospital emergency departments, where there is a lack of research which takes the experiences of end-of-life patients and their relatives into account. Design: a phenomenological qualitative study. Methods: the protocol was approved in December 2016 and will be carried out from December 2016 to December 2020. The Gadamer's philosophical underpinnings will be used in the design and development of the study. The data collection will include participant observation techniques in the Emergency Department, in-depth interviews with terminally-ill patients and focus groups with their relatives. For the data analysis, the field notes and verbatim transcriptions will be read and codified using ATLAS.ti software to search for emerging themes. Discussion: emerging themes that contribute to comprehending the phenomenon of dignity in end-of-life care in the Emergency Department are expected to be found. This study's results could have important implications in the implementation of new interventions in Emergency Departments. These interventions would be focused on improving: the social acceptance of death, environmental conditions, promotion of autonomy and accompaniment, and assumption (takeover) of dignified actions and attitudes (respect for human rights)

Sustained Cytotoxic Response of Peripheral Blood Mononuclear Cells from Unvaccinated Individuals Admitted to the ICU Due to Critical COVID-19 Is Essential to Avoid a Fatal Outcome

The main objective of this study was to determine the influence of the cytotoxic activity of peripheral blood mononuclear cells (PBMCs) on the outcome of unvaccinated individuals with critical COVID-19 admitted to the ICU. Blood samples from 23 individuals were collected upon admission and then every 2 weeks for 13 weeks until death (Exitus group) (n = 13) or discharge (Survival group) (n = 10). We did not find significant differences between groups in sociodemographic, clinical, or biochemical data that may influence the fatal outcome. However, direct cellular cytotoxicity of PBMCs from individuals of the Exitus group against pseudotyped SARS-CoV-2-infected Vero E6 cells was significantly reduced upon admission (−2.69-fold; p = 0.0234) and after 4 weeks at the ICU (−5.58-fold; p = 0.0290), in comparison with individuals who survived, and it did not improve during hospitalization. In vitro treatment with IL-15 of these cells did not restore an effective cytotoxicity at any time point until the fatal outcome, and an increased expression of immune exhaustion markers was observed in NKT, CD4+, and CD8+ T cells. However, IL-15 treatment of PBMCs from individuals of the Survival group significantly increased cytotoxicity at Week 4 (6.18-fold; p = 0.0303). Consequently, immunomodulatory treatments that may overcome immune exhaustion and induce sustained, efficient cytotoxic activity could be essential for survival during hospitalization due to critical COVID-19.This work was supported by the Coordinated Research Activities at the National Center of Microbiology (CNM, Instituto de Salud Carlos III) (COV20_00679) to promote an integrated response against SARS-CoV-2 in Spain (Spanish Ministry of Science and Innovation) that is coordinated by Dr Inmaculada Casas (WHO National Influenza Center of the CNM); a generous donation provided by Chiesi España, S.A.U. (Barcelona, Spain); the Spanish Ministry of Science and Innovation (PID2019-110275RB-I00). The work of Guiomar Casado is financed by CIBERINFEC, co-financed by the European Regional Development Fund (FEDER) “A way to make Europe”. The work of Montserrat Torres is supported by Instituto de Salud Carlos III (COV20_00679). The work of Fernando Ramos Martín is financed by the Spanish Ministry of Science and Innovation (PID2019-110275RB-I00). The work of Mario Manzanares is supported by a pre-doctoral grant from Instituto de Salud Carlos III (ISCIII-PFIS FI20CIII/00021). The work of Lorena Vigón is supported by a pre-doctoral grant from Instituto de Salud Carlos III (FIS PI16CIII/00034-ISCIII-FEDER). The work of Sara Rodríguez-Mora is financed by NIH grant R01AI143567.N

Improvement of catalytic performance of lignin peroxidase for the enhanced degradation of lignocellulose biomass based on the imbedded electron-relay in long-range electron transfer route

Background: Although lignin peroxidase is claimed as a key enzyme in enzyme-catalyzed lignin degradation, in vitro enzymatic degradation of lignin was not easily observed in lab-scale experiments. It implies that other factors may hinder the enzymatic degradation of lignin. Irreversible interaction between phenolic compound and lignin peroxidase was hypothesized when active enzyme could not be recovered after the reaction with degradation product (guaiacol) of lignin phenolic dimer. Results: In the study of lignin peroxidase isozyme H8 from white-rot fungi Phanerochaete chrysosporium (LiPH8), W251 site was revealed to make the covalent coupling with one moiety of monolignolic radical (guaiacol radical) by LC-MS/MS analysis. Hypothetical electron-relay containing W251 residue was newly suggested based on the observation of repressed radical coupling and remarkably lower electron transfer rate for W215A mutant. Furthermore, the retardation of the suicidal radical coupling between the W251 residue and the monolignolic radical was attempted by supplementing the acidic microenvironment around the W251 residue to engineer radical-robust LiPH8. Among many mutants, mutant A242D showed exceptional catalytic performances by yielding 21.1- and 4.9-fold higher increases of k(cat) and k(cat)/K-M values, respectively, in the oxidation of non-phenolic model lignin dimer. Conclusions: A mechanism-based suicide inhibition of LiPH8 by phenolic compounds was firstly revealed and investigated in this work. Radical-robust LiPH8 was also successfully engineered by manipulating the transient radical state of radical-susceptible electron-relay. Radical-robust LiPH8 will play an essential role in degradation of lignin, which will be consequently linked with improved production of sugars from lignocellulose biomass.open

Analysis of relevant technical issues and deficiencies of the existing sensors and related initiatives currently set and working in marine environment. New generation technologies for cost-effective sensors

The last decade has seen significant growth in the field of sensor networks, which are currently collecting large amounts of environmental data. This data needs to be collected, processed, stored and made available for analysis and interpretation in a manner which is meaningful and accessible to end users and stakeholders with a range of requirements, including government agencies, environmental agencies, the research community, industry users and the public. The COMMONSENSE project aims to develop and provide cost-effective, multi-functional innovative sensors to perform reliable in-situ measurements in the marine environment. The sensors will be easily usable across several platforms, and will focus on key parameters including eutrophication, heavy metal contaminants, marine litter (microplastics) and underwater noise descriptors of the MSFD. The aims of Tasks 2.1 and 2.2 which comprise the work of this deliverable are: • To obtain a comprehensive understanding and an up-to-date state of the art of existing sensors. • To provide a working basis on “new generation” technologies in order to develop cost-effective sensors suitable for large-scale production. This deliverable will consist of an analysis of state-of-the-art solutions for the different sensors and data platforms related with COMMONSENSE project. An analysis of relevant technical issues and deficiencies of existing sensors and related initiatives currently set and working in marine environment will be performed. Existing solutions will be studied to determine the main limitations to be considered during novel sensor developments in further WP’s. Objectives & Rationale The objectives of deliverable 2.1 are: • To create a solid and robust basis for finding cheaper and innovative ways of gathering data. This is preparatory for the activities in other WPs: for WP4 (Transversal Sensor development and Sensor Integration), for WP(5-8) (Novel Sensors) to develop cost-effective sensors suitable for large-scale production, reducing costs of data collection (compared to commercially available sensors), increasing data access availability for WP9 (Field testing) when the deployment of new sensors will be drawn and then realized

Molecular and Cellular Mechanisms of Delayed Fracture Healing in Mmp10 (Stromelysin 2) Knockout Mice

The remodeling of the extracellular matrix is a central function in endochondral ossification and bone homeostasis. During secondary fracture healing, vascular invasion and bone growth requires the removal of the cartilage intermediate and the coordinate action of the collagenase matrix metalloproteinase (MMP)-13, produced by hypertrophic chondrocytes, and the gelatinase MMP-9, produced by cells of hematopoietic lineage. Interfering with these MMP activities results in impaired fracture healing characterized by cartilage accumulation and delayed vascularization. MMP-10, Stromelysin 2, a matrix metalloproteinase with high homology to MMP-3 (Stromelysin 1), presents a wide range of putative substrates identified in vitro, but its targets and functions in vivo and especially during fracture healing and bone homeostasis are not well defined. Here, we investigated the role of MMP-10 through bone regeneration in C57BL/6 mice. During secondary fracture healing, MMP-10 is expressed by hematopoietic cells and its maximum expression peak is associated with cartilage resorption at 14 days post fracture (dpf). In accordance with this expression pattern, when Mmp10 is globally silenced, we observed an impaired fracture-healing phenotype at 14 dpf, characterized by delayed cartilage resorption and TRAP-positive cell accumulation. This phenotype can be rescued by a non-competitive transplant of wild-type bone marrow, indicating that MMP-10 functions are required only in cells of hematopoietic linage. In addition, we found that this phenotype is a consequence of reduced gelatinase activity and the lack of proMMP-9 processing in macrophages. Our data provide evidence of the in vivo function of MMP-10 during endochondral ossification and defines the macrophages as the lead cell population in cartilage removal and vascular invasio

Adipose tissue glycogen accumulation is associated with obesity-linked inflammation in humans

Objective: glycogen metabolism has emerged as a mediator in the control of energy homeostasis and studies in murine models reveal that adipose tissue might contain glycogen stores. Here we investigated the physio(patho)logical role of glycogen in human adipose tissue in the context of obesity and insulin resistance. Methods: we studied glucose metabolic flux of hypoxic human adipoctyes by nuclear magnetic resonance and mass spectrometry-based metabolic approaches. Glycogen synthesis and glycogen content in response to hypoxia was analyzed in human adipocytes and macrophages. To explore the metabolic effects of enforced glycogen deposition in adipocytes and macrophages, we overexpressed PTG, the only glycogen-associated regulatory subunit (PP1-GTS) reported in murine adipocytes. Adipose tissue gene expression analysis was performed on wild type and homozygous PTG KO male mice. Finally, glycogen metabolism gene expression and glycogen accumulation was analyzed in adipose tissue, mature adipocytes and resident macrophages from lean and obese subjects with different degrees of insulin resistance in 2 independent cohorts. Results: we show that hypoxia modulates glucose metabolic flux in human adipocytes and macrophages and promotes glycogenesis. Enforced glycogen deposition by overexpression of PTG re-orients adipocyte secretion to a pro-inflammatory response linked to insulin resistance and monocyte/lymphocyte migration. Furthermore, glycogen accumulation is associated with inhibition of mTORC1 signaling and increased basal autophagy flux, correlating with greater leptin release in glycogen-loaded adipocytes. PTG-KO mice have reduced expression of key inflammatory genes in adipose tissue and PTG overexpression in M0 macrophages induces a pro-inflammatory and glycolytic M1 phenotype. Increased glycogen synthase expression correlates with glycogen deposition in subcutaneous adipose tissue of obese patients. Glycogen content in subcutaneous mature adipocytes is associated with BMI and leptin expression. Conclusion: our data establish glycogen mishandling in adipose tissue as a potential key feature of inflammatory-related metabolic stress in human obesity

Nuclear astrophysics with radioactive ions at FAIR

R. Reifarth et al: ; 12 págs.; 9 figs.; Open Access funded by Creative Commons Atribution Licence 3.0 ; Nuclear Physics in Astrophysics VI (NPA6)The nucleosynthesis of elements beyond iron is dominated by neutron captures in the s and r processes. However, 32 stable, proton-rich isotopes cannot be formed during those processes, because they are shielded from the s-process ow and r-process -decay chains. These nuclei are attributed to the p and rp process. For all those processes, current research in nuclear astrophysics addresses the need for more precise reaction data involving radioactive isotopes. Depending on the particular reaction, direct or inverse kinematics, forward or time-reversed direction are investigated to determine or at least to constrain the desired reaction cross sections. The Facility for Antiproton and Ion Research (FAIR) will oer unique, unprecedented opportunities to investigate many of the important reactions. The high yield of radioactive isotopes, even far away from the valley of stability, allows the investigation of isotopes involved in processes as exotic as the r or rp processes.This project was supported by the HGF Young Investigators Project VH-NG-327, EMMI, H4F, HGS-HIRe, JINA, NAVI, DFG and ATHENA.Peer Reviewe

A community challenge for a pancancer drug mechanism of action inference from perturbational profile data

The Columbia Cancer Target Discovery and Development (CTD2) Center is developing PANACEA, a resource comprising dose-responses and RNA sequencing (RNA-seq) profiles of 25 cell lines perturbed with similar to 400 clinical oncology drugs, to study a tumor-specific drug mechanism of action. Here, this resource serves as the basis for a DREAM Challenge assessing the accuracy and sensitivity of computational algorithms for de novo drug polypharmacology predictions. Dose-response and perturbational profiles for 32 kinase inhibitors are provided to 21 teams who are blind to the identity of the compounds. The teams are asked to predict high-affinity binding targets of each compound among similar to 1,300 targets cataloged in DrugBank. The best performing methods leverage gene expression profile similarity analysis as well as deep-learning methodologies trained on individual datasets. This study lays the foundation for future integrative analyses of pharmacogenomic data, reconciliation of polypharmacology effects in different tumor contexts, and insights into network-based assessments of drug mechanisms of action.Peer reviewe