Ghrelin's effects on proinflammatory cytokine mediated apoptosis and their impact on β-cell functionality

Ghrelin is a peptidic hormone, which stimulates cell proliferation and inhibits apoptosis in several tissues, including pancreas. In preclinical stage of type 1 diabetes, proinflammatory cytokines generate a destructive environment for β-cells known as insulitis, which results in loss of β-cell mass and impaired insulin secretion, leading to diabetes. Our aim was to demonstrate that ghrelin could preserve β-cell viability, turnover rate, and insulin secretion acting as a counter balance of cytokines. In the present work we reproduced proinflammatory milieu found in insulitis stage by treating murine cell line INS-1E and rat islets with a cytokine cocktail including IL-1β, IFNγ, and TNFα and/or ghrelin. Several proteins involved in survival pathways (ERK 1/2 and Akt/PKB) and apoptosis (caspases and Bcl-2 protein family and endoplasmic reticulum stress markers) as well as insulin secretion were analyzed. Our results show that ghrelin alone has no remarkable effects on β-cells in basal conditions, but interestingly it activates cell survival pathways, downregulates apoptotic mediators and endoplasmic reticulum stress, and restores insulin secretion in response to glucose when beta-cells are cytokine-exposed. These data suggest a potential role of ghrelin in preventing or slowing down the transition from a preclinical to clinically established diabetes by ameliorating the effects of insulitis on β-cells.This work was funded by a grant by the Andalusian Government (PI 0765-2011).Peer Reviewe

Cross-Resistance to Abiraterone and Enzalutamide in Castration Resistance Prostate Cancer Cellular Models Is Mediated by AR Transcriptional Reactivation

Androgen deprivation therapy (ADT) and novel hormonal agents (NHAs) (Abiraterone and Enzalutamide) are the goal standard for metastatic prostate cancer (PCa) treatment. Although ADT is initially effective, a subsequent castration resistance status (CRPC) is commonly developed. The expression of androgen receptor (AR) alternative splicing isoforms (AR-V7 and AR-V9) has been associated to CRPC. However, resistance mechanisms to novel NHAs are not yet well understood. Androgen-dependent PCa cell lines were used to generate resistant models to ADT only or in combination with Abiraterone and/or Enzalutamide (concomitant models). Functional and genetic analyses were performed for each resistance model by real-time cell monitoring assays, flow cytometry and RT-qPCR. In androgen-dependent PCa cells, the administration of Abiraterone and/or Enzalutamide as first-line treatment involved a critical inhibition of AR activity associated with a significant cell growth inhibition. Genetic analyses on ADT-resistant PCa cell lines showed that the CRPC phenotype was accompanied by overexpression of AR full-length and AR target genes, but not necessarily AR-V7 and/or AR-V9 isoforms. These ADT resistant cell lines showed higher proliferation rates, migration and invasion abilities. Importantly, ADT resistance induced cross-resistance to Abiraterone and/or Enzalutamide. Similarly, concomitant models possessed an elevated expression of AR full-length and proliferation rates and acquired cross-resistance to its alternative NHA as second-line treatment.Instituto de Salud Carlos III PI17/00989European Regional Development Fund "A way to build Europe"Ramon y Cajal - Ministry of Economy and Competitiveness RYC-2015-18382Ministry of Education, Culture and Sport FPU14/05461University of Granad

Sustainable Materials and Biorefinery Chemicals from Agriwastes

This is an open access chapter distributed under the terms of the Creative Commons Attribution License.-- et al.Countries with economies based on agriculture generate vast amounts of low or null value wastes which may even represent an environmental hazard. In our group, agricultural industrial wastes have been converted into value added liquid substances and materials with several aims: decreasing pollution, giving added value to wastes and working in a sustainable manner in which the wastes of an industry can be used as the raw materials of the same or others, as the “cradle to cradle” philosophy states [1]. Sub-products from the agricultural food industry are being employed as renewable low cost raw materials in the preparation of Ecomaterials, designed for use in a number of industrial processes of great interest. Given their origin, these materials may compete with conventional ones since with this process a sustainable cycle is closed, in which the residues of one industry are used as raw materials in the same or other industries [2]. With regards to the composition of the residues produced from agriculture, the pH of soil is of great importance, since plants can only absorb the minerals that are dissolved in water and pH is mandatory for the physical, chemical and biological properties of soil and the main cause of many agronomic questions related to nutrient assimilation [3-5]. Variations of pH modify the solubility of most elements necessary for the development of crops and also influence the microbian activity of soil, which will affect the transformation of elements that are liberated to the soil and can be assimilated to form crops or not [3]. For example at pH lower than 6 or higher than 8 bacterian activities are lowered, the oxidation of nitrogen to nitrate is reduced and the amount of nitrogen available for plant food is decreased. However Al, Fe and manganese are more soluble at low pHs, reaching even toxic concentrations. Potassium and sulphur are easily adsorbed at pH higher than 6, calcium and magnesium between 7 and 8.5 and iron at pH lower than 6. For alkaline pH in soil, the availability of H2PO4-can be reduced through precipitation of phosphorous containing salts withcations such as calcium Ca2+ or magnesium Mg2+. However when soils have acid pH other compounds with HPO42-and iron (Fe2+), aluminium (Al3+) and manganese (Mn2+) can form, with increased solubility. The main factors that influence soil pH are the mineral composition and how it meteorizes, the decomposition of organic matter, how nutrients are partitioned among the solution and aggregates and of course the pluviometryof the zone and atmospheric contamination.Lower pHs are found in places with high pluviometry, with high organic matter decomposition, young soils developed on acid substrates, and places with high atmospheric contamination (acid rain). Depending on the species, crops can benefit from calcareous soils with high calcium carbonate content such as alfalfa, but other plants prefer soils with acid pH such as potatoes, coffee or tobacco. It is clear that different seasons will produce plants with a varying composition depending on the atmospheric conditions and therefore the materials derived from them need to be characterised and analysed to determine their possible uses.Given its multidisciplinary approach, this work is being carried out through the collaboration among national (Institute of Materials Science of Madrid (ICMM, CSIC), Institute of Catalysis (ICP, CSIC), Centre of Molecular Biology Severo Ochoa (UAM-CSIC), Polytechnic University of Madrid (UPM), University at distance (UNED), University Complutense of Madrid (UPM) and international (University of Sheffield and University of Ghent) research groups, in addition to various industries interested in the transformation of their residues and or sub-products into “value added materials”, with whom various research projects have been and are being sponsored by the MICINN and CDTI.Peer Reviewe

Calidad de vida y estrés en estudiantes de medicina en Cajamarca-Perú-2023

Objectives: Determine the influence of quality of life on the stress of medical students at a university in Cajamarca during 2023. Identify the level of quality of life and the degree of stress, and establish the dimensions of quality of life and others. factors that influence stress. Materials and methods: The present study was basic with a quantitative approach, cross-sectional with a correlational method. The student population was 175 students, and the sample was 106 students. The SISCO SV-21 questionnaire with Cronbach's alpha of 0.85 and the WHOQOL-BREF 26 questionnaire with Cronbach's alpha of 0.89 were used. For the treatment of the collected information, descriptive and inferential statistics were used with a level of significance p<0.05 using the Excel statistical package and the Epi Info system. Results: We found 71.70% high levels of stress and 96 % of a low quality of life. A value of p = 0.317 was found with respect to the relationship of the two variables. Regarding the dimensions of the quality of life that predisposes to have high stress, it was found significant to psychological health (p = 0.0025) and PR of 2.88; and social relationships (p= 0.036). Finally, in relation to gender and presentation of stress (significant p of =0.0084) with PR of 1.37. Conclusion: There is no significant correlation between stress and the quality of life of medical students. There are high levels of stress and a feeling of poor quality of life among students. The female sex, mental health and social relationships are significantly related to high levels of stress.Objetivos: Determinar la influencia de la calidad de vida en el estrés de los estudiantes de medicina de una universidad de Cajamarca durante el 2023. Identificar el nivel de calidad de vida y el grado de estrés, y establecer las dimensiones de calidad de vida y otros factores que influyen en el estrés. Materiales y métodos: El presente estudio fue tipo básico con enfoque cuantitativo, de tipo transversal con método correlacional. La población de estudiantes fue de 175 estudiantes, y la muestra fue de 106 estudiantes. Se usó el cuestionario SISCO SV-21 con alfa de Cronbach del 0.85 y el cuestionario WHOQOL-BREF 26 con alfa de Cronbach del 0.89. Para el tratamiento de la información recolectada, se usó la estadística descriptiva e inferencial con un nivel de significancia p<0.05 usando para ello el paquete estadístico Excel y el sistema Epi Info. Resultados: Encontramos un 71,70% altos niveles de estrés y 96% de una calidad de vida baja. Se halló un valor de p = 0.317 con respecto a la relación de las dos variables. Con respecto a las dimensiones de la calidad de vida que predispone a tener estrés alto, se encontró significativo a la salud psicológica (p = 0.0025) y RP de 2.88; y las relaciones sociales (p= 0.036). Finalmente, en relación a sexo y presentación de estrés (p significativo de =0,0084) con RP de 1.37. Conclusión: No existe correlación significativa entre el estrés y la calidad de vida de los estudiantes de medicina, Existen elevados niveles de estrés y de sensación de mala calidad de vida entre los estudiantes. El sexo femenino, la salud mental y las relaciones sociales se relacionan significativamente con elevados de estrés

Hospital Virtual: Sistema de información clínica y telecuidado de pacientes VIH/SIDA basado en tecnologías Web 2.0

Este artículo describe el desarrollo de un nuevo sistema de información clínica y telecuidado de pacientes VIH/SIDA que se encuentra implantado en rutina clínica dentro del Servicio de Enfermedades Infecciosas del Hospital Clínic de Barcelona. El proyecto surge ante la necesidad de unificar el sistema de información departamental del servicio y un sistema de telemedicina instalado en el hospital en 2004. Para ello se han diseñado e implementado nuevas bases de datos y dos sistemas específicos para uso de profesionales y pacientes. Además, se ha realizado una integración con el Sistema de Información del Hospital (HIS) permitiendo el acceso a todos los datos requeridos de los pacientes desde una única aplicación. Este nuevo sistema está al servicio de más de 70 profesionales sanitarios que realizan una media de 150 consultas al día disponiendo de información clínica de más de 8000 pacientes

Progression of regional lung strain and heterogeneity in lung injury: assessing the evolution under spontaneous breathing and mechanical ventilation

Indexación ScopusBackground: Protective mechanical ventilation (MV) aims at limiting global lung deformation and has been associated with better clinical outcomes in acute respiratory distress syndrome (ARDS) patients. In ARDS lungs without MV support, the mechanisms and evolution of lung tissue deformation remain understudied. In this work, we quantify the progression and heterogeneity of regional strain in injured lungs under spontaneous breathing and under MV. Methods: Lung injury was induced by lung lavage in murine subjects, followed by 3 h of spontaneous breathing (SB-group) or 3 h of low Vt mechanical ventilation (MV-group). Micro-CT images were acquired in all subjects at the beginning and at the end of the ventilation stage following induction of lung injury. Regional strain, strain progression and strain heterogeneity were computed from image-based biomechanical analysis. Three-dimensional regional strain maps were constructed, from which a region-of-interest (ROI) analysis was performed for the regional strain, the strain progression, and the strain heterogeneity. Results: After 3 h of ventilation, regional strain levels were significantly higher in 43.7% of the ROIs in the SB-group. Significant increase in regional strain was found in 1.2% of the ROIs in the MV-group. Progression of regional strain was found in 100% of the ROIs in the SB-group, whereas the MV-group displayed strain progression in 1.2% of the ROIs. Progression in regional strain heterogeneity was found in 23.4% of the ROIs in the SB-group, while the MV-group resulted in 4.7% of the ROIs showing significant changes. Deformation progression is concurrent with an increase of non-aerated compartment in SB-group (from 13.3% ± 1.6% to 37.5% ± 3.1%), being higher in ventral regions of the lung. Conclusions: Spontaneous breathing in lung injury promotes regional strain and strain heterogeneity progression. In contrast, low Vt MV prevents regional strain and heterogeneity progression in injured lungs. © 2020, The Author(s).https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-020-00725-

HPV-negative Penile Intraepithelial Neoplasia (PeIN) With Basaloid Features.

Most human papillomavirus (HPV)-independent penile squamous cell carcinomas (PSCCs) originate from an intraepithelial precursor called differentiated penile intraepithelial neoplasia, characterized by atypia limited to the basal layer with marked superficial maturation. Previous studies in vulvar cancer, which has a similar dual etiopathogenesis, have shown that about one fifth of HPV-independent precursors are morphologically indistinguishable from high-grade squamous intraepithelial lesions (HSILs), the precursor of HPV-asssociated carcinomas. However, such lesions have not been described in PSCC. From 2000 to 2021, 55 surgical specimens of PSCC were identified. In all cases, thorough morphologic evaluation, HPV DNA detection, and p16, p53, and Ki-67 immunohistochemical (IHC) staining was performed. HPV-independent status was assigned based on both negative results for p16 IHC and HPV DNA. Thirty-six of the 55 PSCC (65%) were HPV-independent. An intraepithelial precursor was identified in 26/36 cases (72%). Five of them (19%) had basaloid features, morphologically indistinguishable from HPV-associated HSIL. The median age of the 5 patients was 74 years (range: 67 to 83 y). All 5 cases were p16 and DNA HPV-negative. Immunohistochemically, 3 cases showed an abnormal p53 pattern, and 2 showed wild-type p53 staining. The associated invasive carcinoma was basaloid in 4 cases and the usual (keratinizing) type in 1. In conclusion, a small proportion of HPV-independent PSCC may arise on adjacent intraepithelial lesions morphologically identical to HPV-associated HSIL. This unusual histologic pattern has not been previously characterized in detail in PSCC. p16 IHC is a valuable tool to identify these lesions and differentiate them from HPV-associated HSIL