Suppression of molten salt corrosion by plasma sprayed Ni3Al coatings

Corrosion behaviour of stainless steel 347 was investigated in a molten nitrate salt (60 wt% NaNO3 + 40 wt% KNO3) immersion at 565 °C for up to 3000 h. A growth of stratified oxide layers consisting of NaFeO2, Fe2O3 and Fe3O4 was observed on the stainless steel surface with a constant gravimetric corrosion rate of ~ 0.4 µm/year. The feasibility of using Ni3Al coatings deposited by means of air plasma spray for suppression of corrosion was investigated. Ni3Al coatings were observed to undergo a fast oxidation with a corrosion rate of ~ 2.7 µm/year in the first 500 h, and subsequently stabilise between 500 and 3000 h with no observable changes in microstructure, composition and weight at a corrosion rate of ~ 0.02 µm/year. The results presented in this study strongly suggest that Ni3Al coating suppresses the formation of oxide layers on the surface of stainless steel substrates and can be used as protection against corrosion in the presence of molten nitrate salts, which is of relevance to thermal energy storage applications.European Union’s Horizon 2020 research and innovation programme grant number 645725. Engineering and Physical Research Council grant number EP/L016389/1

Repurposing Study of 4-Acyl-1-phenylaminocarbonyl-2-substituted-piperazine Derivatives as Potential Anticancer Agents-In Vitro Evaluation against Breast Cancer Cells

first_pagesettingsOrder Article Reprints Open AccessArticle Repurposing Study of 4-Acyl-1-phenylaminocarbonyl-2-substituted-piperazine Derivatives as Potential Anticancer Agents—In Vitro Evaluation against Breast Cancer Cells by Emilio Guillén-Mancina 1,†,María del Rosario García-Lozano 2,3,†ORCID,Estefanía Burgos-Morón 1ORCID,Sarah Mazzotta 2,4ORCID,Pablo Martínez-Aguado 2,3,5,6,José Manuel Calderón-Montaño 1ORCID,José Manuel Vega-Pérez 2,Miguel López-Lázaro 1ORCID,Fernando Iglesias-Guerra 2,* andMargarita Vega-Holm 2,*ORCID 1 Department of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain 2 Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain 3 Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, CSIC, University of Seville, 41013 Seville, Spain 4 Department of Chemistry, University of Milan, 20133 Milan, Italy 5 Infectious Diseases and Microbiology Clinical Unit, University Hospital Virgen Macarena, 41009 Seville, Spain 6 Departament of Medicine, School of Medicine, University of Seville, 41012 Seville, Spain * Authors to whom correspondence should be addressed. † These authors contributed equally to this work. Int. J. Mol. Sci. 2023, 24(23), 17041; https://doi.org/10.3390/ijms242317041 Original submission received: 31 January 2023 / Resubmission received: 3 November 2023 / Revised: 21 November 2023 / Accepted: 28 November 2023 / Published: 1 December 2023 (This article belongs to the Special Issue Novel Molecular Pathways in Oncology) Downloadkeyboard_arrow_down Browse Figures Versions Notes Abstract Breast cancer is the most common type of cancer in women. Although current treatments can increase patient survival, they are rarely curative when the disease is advanced (metastasis). Therefore, there is an urgent need to develop new cytotoxic drugs with a high selectivity toward cancer cells. Since repurposing approved drugs for cancer therapy has been a successful strategy in recent years, in this study, we screened a library of antiviral piperazine-derived compounds as anticancer agents. The compounds included a piperazine ring and aryl urea functions, which are privileged structures present in several anti-breast cancer drugs. The selective cytotoxic activity of a set of thirty-four 4-acyl-2-substituted piperazine urea derivatives against MCF7 breast cancer cells and MCF 10A normal breast cells was determined. Compounds 31, 32, 35, and 37 showed high selective anticancer activity against breast cancer cells and were also tested against another common type of cancer, non-small cell lung cancer (A549 lung cancer cells versus MRC-5 lung normal cells). Compounds 35 and 37 also showed selectivity against lung cancer cells. These results suggest that compounds 35 and 37 may be promising hit compounds for the development of new anticancer agents.Ministerio de Ciencia, Innovación y Universidades de España, Plan Estatal 2017-2020 - I+D+i PID2019-104767RB-I00Junta de Andalucía - 2017/CTS-657 y 2019/CTS-657Universidad de Sevilla, V Plan Propio de Investigación y Transferencia” - PPI2015-II.2Universidad de Sevilla, VI Plan Propio de Investigación y Transferencia” - VIPPIT-2019-I.5 y VIPPIT-2020-I.5Universidad de Sevilla, VII Plan Propio de Investigación y Transferencia” - VIIPPIT-2023-I.

Enfermedades hematológicas graves en la unidad de cuidados intensivos pediátricos pinareña

Introduction: patients with hematological diseases admitted in intensive care units have special characteristics because they have complex diseases requiring a multidisciplinary approach. Intensive care has contributed to the improvement of their survival by the use of new diagnostic and therapeutic strategies. Objective: to elaborate a set of rules to perform the diagnostic and therapeutic procedures on the severe types of hematological diseases. Method: a cross-sectional and descriptive research was carried out comprising the patients suffering from hematological diseases treated in the intensive care service at Pepe Portilla Provincial Pediatric Teaching Hospital, Pinar del Río between the years 2011 to 2015. The information was processed using the method of descriptive statistics with a computer program and processed using the statistical software EPINFO. Results: 64% of the patients were male, the group of ages from 5-10 years old predominated, acute lymphoblastic leukemia was the most frequent disease and myeloblastic showed the highest mortality rate. Septic shock (25%), acute respiratory failure (19.4%), and respiratory distress (16.6%) were the main complications presented in this service; neutropenia was the most influential factor of the syndrome due to the systemic inflammatory response. Conclusion: malignant diseases sometimes present a serious evolution, requiring admission to intensive care, leukemias are well-known within them. Introducción: los pacientes con enfermedades hematológicas que ingresan en cuidados intensivos, tienen características especiales por tener enfermedades complejas que necesitan enfoque multidisciplinario. Los cuidados intensivos han contribuido a mejorar la supervivencia de éstos, por el uso de nuevas estrategias diagnósticas y terapéuticas.Objetivo: elaborar un protocolo de procederes diagnósticos y terapéuticos sobre las formas graves de las enfermedades hematológicas.Método: se realizó una investigación transversal y descriptiva de los pacientes con enfermedades hematológicas atendidos en el servicio de terapia intensiva del Hospital Pediátrico Provincial Docente “Pepe Portilla” de Pinar del Río entre los años 2011 a 2015. La información se procesó empleando el método de Estadística Descriptiva con un programa computarizado y procesado mediante el software estadístico EPINFO. Resultados: el 64% de los pacientes fueron del sexo masculino, predominando el grupo de 5-10 años de edad, siendo la leucemia linfoblástica aguda la enfermedad más frecuente y la mieloblástica, la de mayor mortalidad. Las principales complicaciones que motivaron ingreso en el servicio fueron el shock séptico (25%), la insuficiencia respiratoria aguda (19,4%) y el distres respiratorio (16,6%), la neutropenia resultó ser el factor  más influyente en el síndrome de respuesta inflamatoria sistémica.Conclusiones: las enfermedades malignas en ocasiones presentan una evolución grave, requiriendo ingreso en cuidados intensivos, se destacan las leucemias dentro de las mismas.

Calidad de la atención médica según PRISM III en la unidad de cuidados intensivos pediátricos

Introducción: los índices de predicción de mortalidad permiten interpretar la información derivada del ejercicio clínico, facilitar la estimación del éxito en el diagnóstico y la elección de determinada terapéutica. Objetivo: evaluar la calidad de la atención médica hospitalaria mediante la escala de riesgo de mortalidad pediátrica en unidades de cuidados intensivos. Método: se incluyeron en el estudio 680 niños ingresados desde noviembre de 2013 hasta agosto de 2015, el muestreo se realizó de forma intencionada, basado en criterios de inclusión y exclusión. Para el procesamiento de los datos se utilizó el programa SPSS 11.1 para Windows, para calcular estadísticas descriptivas: medidas de tendencia central (media) y de dispersión (desviación típica). Las variables categóricas se analizaron a través de la prueba de asociación chi cuadrado (X2). Se calculó la especificidad y sensibilidad de este score de mortalidad pediátrico. Para todas las pruebas se tomó como significativo un valor de p <0,05.  Resultados: el 57,2% fueron del sexo masculino, el 53,2% eran menores de 5 años, seguidos por 34,4% entre 10 a 18 años, siendo las enfermedades  respiratorias con un 31.1%, las más comunes al ingreso. Del total de pacientes estudiados, 642 presentaron evolución favorable, 53.8% estaban eutróficos. Según la escala pronostica, el 72% de los casos mostraron bajo riesgo de fallecer. Conclusiones: la desnutrición incrementa la probabilidad de fallecimiento y que el score pronóstico utilizado es una herramienta útil y necesaria pues predice en un alto porcentaje el riesgo de morir, el cual tuvo mayor especificidad que sensibilidad

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Interlaboratory study on lipid oxidation during accelerated storage trials with rapeseed and sunflower oil analyzed by conjugated dienes as primary oxidation products

11 Páginas.-- 5 Figuras.-- 2 Tablas.-- Material suplementarioAccelerated storage tests are frequently used to assess the oxidative stability of foods and related systems due to its reproducibility. Various methods and experimental conditions are used to measure lipid oxidation. Differences between laboratories make it necessary to determine the repeatability and reproducibility of oxidation tests performed under the same conditions. The objective of the present interlaboratory study was to evaluate the outcome of a storage test for two different bulk oils, sunflower oil (SFO) and rapeseed oil (RSO), during a period of 9 weeks at 20°C, 30°C, 40°C, and 60°C. Sixteen laboratories were provided with bottled oils and conducted the storage tests according to a detailed protocol. Lipid oxidation was monitored by the formation of conjugated dienes (CD) and the activation energy (Ea) was determined for comparative purposes and statistically evaluated. An increase in CD formation was observed for both oils when the storage temperature was increased in all laboratories. The Ea,1 ranged from 47.9 to 73.3 kJ mol−1 in RSO and from 27.8 to 62.6 kJ mol−1 in SFO, with average values of 58.2 and 46.8 kJ mol−1, respectively. The reproducibility coefficients were 10.9% and 18.2% for RSO and SFO, respectively. Practical applications: In order to compare results on oxidative stability of foods derived from different studies, the reproducibility of storage tests and methods employed to evaluate the oxidation level should be considered. This study provides fundamental data on the reproducibility of lipid oxidation under accelerated storage conditions and defines important parameters to be considered for the conduction of experiments.Open access funding enabled and organized by Projekt DEAL. We thank Brökelmann + Co – Oelmühle GmbH + Co for the donation of the vegetable oils. The authors gratefully acknowledge Lina Stuthmann from the Food Technology Division, Kiel University and Inge Holmberg from the National Food Institute, Technical University of Denmark for their skillful help.Peer reviewe

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes