Biofabrication of a tri-layered 3D-bioprinted CSC-based malignant melanoma model for personalized cancer treatment

Conventional in vitro cancer models do not accurately reproduce the tumor microenvironment (TME), so three-dimensional (3D)-bioprinting represents an excellent tool to overcome their limitations. Here, two multicellular tri-layered malignant melanoma (MM) models composed by cancer stem cells (CSCs) isolated from a MM established cell line or a primary-patient derived cell line, fibroblasts, mesenchymal stem cells, and endothelial cells, embedded within an agarose-collagen type I hydrogel were bioprinted. Embedded-cells showed high proliferation and metabolic activity, and actively remodeled their TME. MM hydrogels displayed similar rheological properties that skin and were able to support an early onset of vascularization. Besides, MM hydrogels displayed different response to vemurafenib compared with cell cultures, and supported tumorigenesis in murine xenotransplant achieving more mimetic in vivo models. For the first time a tri-layered 3D-bioprinted CSC-based human MM model is developed recreating TME in vitro and in vivo and response to treatment, being useful for precision treatment regimens against MM.Consejería de Salud y Familias de la Junta de Andalucía (Project No. PIN-0224-2019)Consejería de Economía, Conocimiento, Empresas y Universidad de la Junta de Andalucía (FEDER Funds, Projects PY18-FR-2470, B-CTS-230-UGR18, A-CTS-180-UGR20, PYC20 RE 015 UGR and P18-FR-2465),Ministry de Economía y Competitividad, Instituto de Salud Carlos III (FEDER funds, Projects Nos. DTS19/00145 and DTS21/00098)Chair ‘Doctors Galera-Requena in cancer stem cell research’ (CMCCTS963)Universidad de Granada/CBUA.Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020— FEDER funds—Ref: DOC_01574)

Análisis de las causas de muerte en pacientes con síndrome mielodiplásico : experiencia de un centro

Los síndrome mielodisplásicos (SMD) son un conjunto de neoplasias hematológicas muy heterogéneas en cuanto a evolución clínica y pronóstico, que van desde enfermedades indolentes hasta enfermedades agresivas, con una rápida progresión a LMA y una supervivencia inferior a un año. Las causas de muerte (CDM) de los SMD no están bien estudiadas, particularmente la CDM no leucémica. La importancia de conocer las CDM, radica en la implicación terapeútica. En este estudio se demuestra que la mayoría de los SMD, independientemente del grupo de riesgo, fallecen de causas relacionadas con el SMD, lo que justificaría una intevención terapeútica precoz.Els síndromes mielodisplàsiques (SMD) són un conjunt de neoplàsies hematològiques molt heterogènies en quant a evolució clínica i pronòstic, que van des de malalties indolents fins a malalties agressivesñ amb una ràpida progressió a LMA i supervivència inferior a un any. Les causes de mort (CDM) dels SMD no estan ben estudiades, particularment la CDM no leucèmica. La importància de conèixer les CDM, rau en la implicació terapèutica. En aquest estudi es demostra que la majoria dels SMD, independentment del grup de risc, moren de causes relacionades amb el SMD, el que justificaria una intevenció terapèutica precoç

Paving with Precast Concrete Made with Recycled Mixed Ceramic Aggregates: A Viable Technical Option for the Valorization of Construction and Demolition Wastes (CDW)

materialsArticle Paving with Precast Concrete Made with Recycled Mixed Ceramic Aggregates: A Viable Technical Option for the Valorization of Construction and Demolition Wastes (CDW) Andrés Juan-Valdés 1,* , Julia García-González 2, Desirée Rodríguez-Robles 3, Manuel Ignacio Guerra-Romero 1, Fernando López Gayarre 4, Nele De Belie 5 and Julia M. Morán-del Pozo 1 1 Department of Agricultural Engineering and Sciencies, University of León, 24071 León, Spain; [email protected] (M.I.G.-R.); [email protected] (J.M.M.-d.P.) 2 Department of Agriculture and Feeding, University of La Rioja, 26006 Logroño, Spain; [email protected] 3 Department of Agronomy and Forestry Engineering, University of Extremadura, 06007 Badajoz, Spain; [email protected] 4 Department of Construction, Campus de Gijón, University of Oviedo, 33203 Gijón, Spain; [email protected] 5 Magnel Laboratory for Concrete Research, Ghent University, 9052 Ghent, Belgium; [email protected] * Correspondence: [email protected]; Tel.: +34-987-291000 Received: 4 December 2018; Accepted: 18 December 2018; Published: 21 December 2018 Abstract: This research aimed to prove the feasibility of producing two types of precast elements widely used in construction, such as curbstones and paving blocks, using recycled concrete made with a 50% substitution of the natural gravel by recycled mixed aggregates with a significant ceramic content (>30%). In order to prove the quality of such mass concrete recycled precast elements, two different mixes were used: the first one was a conventional concrete mix provided by Prefabricados de Hormigón Pavimentos Páramo S.L., one of the collaborating companies in this study, and the other was a mixture in which wt 50% of the natural coarse aggregates were substituted for recycled mixed aggregates ceramic (RMAc). This recycled aggregate is a heterogeneous mixture of unbound aggregates, concrete, ceramic, etc., used as a secondary recycled aggregate and commonly produced in a lot of recycling plants in many European countries. This material was supplied by Tecnología y Reciclado S.L., the other collaborating company. Both mixtures were representative in order to establish the comparative behavior between them, taking into account that smaller percentages of replacement of the natural with recycled aggregates will also produce good results. This percentage of substitution represents a high saving of natural resources (gravel) and maintains a balanced behavior of the recycled concrete, so this new material can be considered to be a viable and reliable option for precast mass concrete paving elements. The characterization of the recycled precast elements, covering mechanical, microstructural, and durability properties, showed mostly similar behavior when compared to the analogous industrially-produced pieces made with conventional concrete.This work has been financially supported by the Spanish Ministry of Economy and Competitiveness through the research projects grants BIA2013-48876-C3-3-R and BIA2017-83526-R.The authors would like to thanks the companies Prefabricados de Hormigón Pavimentos Páramo S.L. and TEC-REC: Tecnología y Reciclado S.L., who participated in this study

Effect of pores on the mechanical and durability properties on high strength recycled fine aggregate mortar

[EN] Larger consumption of natural fine aggregates (NFA) leads to an increase in cost, energy, and negative environmental impact. On the contrary, the larger production of construction waste results in the generation of recycled fine aggregate (RFA), which requires safe disposal. The aim of study, is to the hunt for such alternatives, compares the mortar mechanical and durability properties with and without RFA. High strength mortar specimens were produced with mix proportion as 1:3 using RFA as partial replacement for NFA as 0%, 25%, 50% and 100%. The mechanical and durability performance of all specimens was assessed in the terms of compressive strength, flexural strength, water absorption and mercury intrusion porosimetry. Mechanical performance is confirmed by microscopic studies. The main results display that the mortar with 25% of RFA, performed better, which are related to pore structures and their distribution. It is noted that the, pores also increase with the increase in RFA content. The effect of pores on the strength and their relationships are assessed.SIAuthor wish to thank for the supports and guidance given by faculties from University of Leon, Leon, Spain and Coimbatore Institute of Technology, Coimbatore, Indi

Unraveling the Potential of miRNAs from CSCs as an Emerging Clinical Tool for Breast Cancer Diagnosis and Prognosis

This research was funded by Consejería de Salud y Familias de la Junta de Andalucía (project no. PIN-0224-2019 and PEMP-0205-2022 FEDER funds); the Ministerio de Ciencia e Innovación (project no. PID2022-140151OB-C22); the Convocatoria de Proyectos Intramurales ibs.GRANADA (project no. INTRAIBS-2020-1 and INTRAIBS-2021-09) and by the Chair “Doctors Galera-Requena in cancer stem cell research” (CMC-CTS963).Breast cancer (BC) is the most diagnosed cancer in women and the second most common cancer globally. Significant advances in BC research have led to improved early detection and effective therapies. One of the key challenges in BC is the presence of BC stem cells (BCSCs). This small subpopulation within the tumor possesses unique characteristics, including tumor-initiating capabilities, contributes to treatment resistance, and plays a role in cancer recurrence and metastasis. In recent years, microRNAs (miRNAs) have emerged as potential regulators of BCSCs, which can modulate gene expression and influence cellular processes like BCSCs' self-renewal, differentiation, and tumor-promoting pathways. Understanding the miRNA signatures of BCSCs holds great promise for improving BC diagnosis and prognosis. By targeting BCSCs and their associated miRNAs, researchers aim to develop more effective and personalized treatment strategies that may offer better outcomes for BC patients, minimizing tumor recurrence and metastasis. In conclusion, the investigation of miRNAs as regulators of BCSCs opens new directions for advancing BC research through the use of bioinformatics and the development of innovative therapeutic approaches. This review summarizes the most recent and innovative studies and clinical trials on the role of BCSCs miRNAs as potential tools for early diagnosis, prognosis, and resistance.Consejería de Salud y Familias de la Junta de Andalucía PIN-0224-2019, PEMP-0205-2022 FEDERMinisterio de Ciencia e Innovación PID2022-140151OB-C22Convocatoria de Proyectos Intramurales ibs.GRANADA INTRAIBS-2020-1, INTRAIBS-2021-09Chair “Doctors Galera-Requena in cancer stem cell research” CMC-CTS96

Unique expression of the atypical mitochondrial subunit NDUFA4L2 in cerebral pericytes fine tunes HIF activity in response to hypoxia

A central response to insufficient cerebral oxygen delivery is a profound reprograming of metabolism, which is mainly regulated by the Hypoxia Inducible Factor (HIF). Among other responses, HIF induces the expression of the atypical mitochondrial subunit NDUFA4L2. Surprisingly, NDUFA4L2 is constitutively expressed in the brain in non-hypoxic conditions. Analysis of publicly available single cell transcriptomic (scRNA-seq) data sets coupled with high-resolution multiplexed fluorescence RNA in situ hybridization (RNA F.I.S.H.) revealed that in the murine and human brain NDUFA4L2 is exclusively expressed in mural cells with the highest levels found in pericytes and declining along the arteriole-arterial smooth muscle cell axis. This pattern was mirrored by COX4I2, another atypical mitochondrial subunit. High NDUFA4L2 expression was also observed in human brain pericytes in vitro, decreasing when pericytes are muscularized and further induced by HIF stabilization in a PHD2/PHD3 dependent manner. In vivo, Vhl conditional inactivation in pericyte targeting Ng2-cre transgenic mice dramatically induced NDUFA4L2 expression. Finally NDUFA4L2 inactivation in pericytes increased oxygen consumption and therefore the degree of HIF pathway induction in hypoxia. In conclusion our work reveals that NDUFA4L2 together with COX4I2 is a key hypoxic-induced metabolic marker constitutively expressed in pericytes coupling mitochondrial oxygen consumption and cellular hypoxia respons

Evaluation of Phenolic Compounds and Pigments Content in Yellow Bell Pepper Wastes

This research was supported by the Aula de Empresa "Vellsam-UGR para la Innovacion en Nutricion y Salud". Vito Verardo thanks the Spanish Ministry of Economy and Competitiveness (MINECO) for "Ramon y Cajal" contract (RYC-2015-18795).Bell peppers are one of the most important species consumed and cultivated in Spain. Peppers are a source of carotenoids and phenolic compounds widely associated with biological activities such as antimicrobial, antiseptic, anticancer, counterirritant, cardioprotective, appetite stimulator, antioxidant, and immunomodulator. However, undersized and damaged fruits are usually wasted. Thus, in order to evaluate the phenolic content, a Box–Behnken design has been carried out to optimize the extraction from Capsicum annuum yellow pepper by ultrasound-assisted extraction (UAE). The independent factors were time (min), ethanol/water (% v/v) and solvent/sample ratio (v/w). The model was validated by ANOVA and confirmed. Furthermore, the whole pepper and the pepper without peduncles and seeds were extracted using optimal conditions and characterized by HPLC-ESI-TOF-MS. Moreover, their antioxidant activities, measured by three different methods (DPPH, ABTS, and FRAP), carotenoid composition, assessed by HPLC-MS, and chlorophyll content, assessed by a spectrophotometric method, were compared. A total of 38 polar compounds were found of which seven have been identified in pepper fruit extracts for the first time. According to the results, whole pepper (WP) samples presented higher content in phenolic acids; meanwhile, the edible portion (EP) was higher in flavonoids. No differences were found in the antioxidant activity except for the FRAP assay where the WP sample showed higher radical scavenging activity. EP samples showed the highest content of carotenoids and WP ones in chlorophylls.Aula de Empresa "Vellsam-UGR para la Innovacion en Nutricion y Salud"Spanish Ministry of Economy and Competitiveness (MINECO) for "Ramon y Cajal" RYC-2015-1879

Género e influencia de factores socioeconómicos sobre la obesidad en España

Análisis realizado a partir de la recientemente publicada Encuesta Nacional de Salud 2017. Los datos son originales e inéditos.Introducción. La obesidad es un problema de salud pública. Algunos determinantes socioeconómicos pueden influir sobre la obesidad. Es necesario evaluar si afectan igualmente a hombres y mujeres. Metodología. Encuesta Nacional de Salud 2017 (10.031 hombres y 11.393 mujeres con 18 o más años). Variables dependientes: sobrepeso (IMC>=25 Kg/m2); obesidad (IMC>=30 Kg/m2). Variables independientes: nivel de educación, clase social e ingresos mensuales por persona y hogar. Se calcularon prevalencias de sobrepeso y obesidad por sexo y grupos de edad. Se evaluó el efecto de las variables independientes mediante modelos de regresión logística. Se evaluó la asociación entre sobrepeso, obesidad, y salud autopercibida mediante modelos de regresión logística. Todos los análisis se realizaron por separado para hombres y mujeres. Resultados. Prevalencia de sobrepeso: 56,5% (48,7 % en mujeres; 65,2 % en hombres). Prevalencia de obesidad: 18,2 % (17,5 % en mujeres; 18,9 % en hombres). En los hombres no se encontró asociación entre clase social y sobrepeso u obesidad; los ingresos mensuales menores de 600 € se asociaron con obesidad. En las mujeres, las asociaciones entre las tres variables socioeconómicas y sobrepeso y obesidad resultaron estadísticamente significativas. La OR de salud autopercibida mala era 1,42 entre personas con sobrepeso (1,16 en hombres; 1,64 en mujeres), y 1,69 entre personas con obesidad (1,49 en hombres; 1,91 en mujeres). Todas las OR resultaron estadísticamente significativas. Conclusiones. La influencia de factores socioeconómicos sobre sobrepeso y obesidad no es igual en hombres y mujeres. Es necesario tener en cuenta el género a la hora de planificar actuaciones contra la obesidad.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Therapeutic Management and Long-Term Outcome of Hy-Perthyroidism in Patients with Antithyroid-Induced Agranu-Locytosis: A Retrospective, Multicenter Study

Background: Antithyroid drug-induced agranulocytosis (AIA) (neutrophils <500/mu L) is a rare but serious complication in the treatment of hyperthyroidism. Methodology: Adult patients with AIA who were followed up at 12 hospitals in Spain were retrospectively studied. A total of 29 patients were studied. The etiology of hyperthyroidism was distributed as follows: Graves' disease (n = 21), amiodarone-induced thyrotoxicosis (n = 7), and hyperfunctioning multinodular goiter (n = 1). Twenty-one patients were treated with methimazole, as well as six patients with carbimazole and two patients with propylthiouracil. Results: The median (IQR) time to development of agranulocytosis was 6.0 (4.0-11.5) weeks. The most common presenting sign was fever accompanied by odynophagia. All of the patients required admission, reverse isolation, and broad-spectrum antibiotics; moreover, G-CSF was administered to 26 patients (89.7%). Twenty-one patients received definitive treatment, thirteen patients received surgery, nine patients received radioiodine, and one of the patients required both treatments. Spontaneous normalization of thyroid hormone values occurred in six patients (four patients with amiodarone-induced thyrotoxicosis and two patients with Graves' disease), and two patients died of septic shock secondary to AIA. Conclusions: AIA is a potentially lethal complication that usually appears around 6 weeks after the initiation of antithyroid therapy. Multiple drugs are required to control hyperthyroidism before definitive treatment; additionally, in a significant percentage of patients (mainly in those treated with amiodarone), hyperthyroidism resolved spontaneously

Cross Sectional and Case-Control Study to Assess Time Trend, Gender Differences and Factors Associated with Physical Activity among Adults with Diabetes: Analysis of the European Health Interview Surveys for Spain (2014 & 2020)

We aim to assess the time trend from 2014 to 2020 in the prevalence of physical activity (PA), identify gender differences and sociodemographic and health-related factors associated with PA among people with diabetes, and compare PA between people with and without diabetes. (2) Methods: We conducted a cross-sectional and a case–control study using as data source the European Health Interview Surveys for Spain (EHISS) conducted in years 2014 and 2020. The presence of diabetes and PA were self-reported. Covariates included socio-demographic characteristics, health-related variables, and lifestyles. To compare people with and without diabetes, we matched individuals by age and sex. (3) Results: The number of participants aged ≥18 years with self-reported diabetes were 1852 and 1889 in the EHISS2014 and EHISS2020, respectively. The proportion of people with diabetes that had a medium or high frequency of PA improved from 48.3% in 2014 to 52.6% in 2020 (p = 0.009), with 68.5% in 2014 and 77.7% in 2020 being engaged in two or more days of PA (p 30 were associated to less PA. (4) Conclusions: The time trend of PA among Spanish adults with diabetes is favorable but insufficient. The prevalence of PA in this diabetes population is low and does not reach the levels of the general population. Gender differences were found with significantly more PA among males with diabetes. Our result could help to improve the design and implementation of public health strategies to improve PA among people with diabetes