Mechanical behavior of alkali-cement as function of the temperature.

This investigation reports on a comparative study of the mechanical behavior at different temperatures of three different alkali-activated fly ash pastes chemically activated using sodium silicate. A control Portland cement (OPC) was used as a reference. In an attempt to simulate the conditions prevailing in the event of accidental fire, post-thermal mechanical tests were performed to determine the residual strength. It has therefore been established that FA based cements can be fabricated for construction purposes and these materials have great potential for fire resistance applications

Fractal dimension analysis of malignant and benign endobronchial ultrasound nodes

Background: Endobronchial ultrasonography (EBUS) has been applied as a routine procedure for the diagnostic of hiliar and mediastinal nodes. The authors assessed the relationship between the echographic appearance of mediastinal nodes, based on endobronchial ultrasound images, and the likelihood of malignancy.; Methods: The images of twelve malignant and eleven benign nodes were evaluated. A previous processing method was applied to improve the quality of the images and to enhance the details. Texture and morphology parameters analyzed were: the image texture of the echographies and a fractal dimension that expressed the relationship between area and perimeter of the structures that appear in the image, and characterizes the convoluted inner structure of the hiliar and mediastinal nodes.; Results: Processed images showed that relationship between log perimeter and log area of hilar nodes was lineal (i.e. perimeter vs. area follow a power law). Fractal dimension was lower in the malignant nodes compared with non-malignant nodes (1.47(0.09), 1.53(0.10) mean(SD), Mann-Whitney U test p < 0.05)).; Conclusion: Fractal dimension of ultrasonographic images of mediastinal nodes obtained through endobronchial ultrasound differ in malignant nodes from non-malignant. This parameter could differentiate malignat and non-malignat mediastinic and hiliar nodes.Peer ReviewedPostprint (published version

CDC42EP5/BORG3 modulates SEPT9 to promote actomyosin function, migration, and invasion.

Fast amoeboid migration is critical for developmental processes and can be hijacked by cancer cells to enhance metastatic dissemination. This migratory behavior is tightly controlled by high levels of actomyosin contractility, but how it is coupled to other cytoskeletal components is poorly understood. Septins are increasingly recognized as novel cytoskeletal components, but details on their regulation and contribution to migration are lacking. Here, we show that the septin regulator Cdc42EP5 is consistently required for amoeboid melanoma cells to invade and migrate into collagen-rich matrices and locally invade and disseminate in vivo. Cdc42EP5 associates with actin structures, leading to increased actomyosin contractility and amoeboid migration. Cdc42EP5 affects these functions through SEPT9-dependent F-actin cross-linking, which enables the generation of F-actin bundles required for the sustained stabilization of highly contractile actomyosin structures. This study provides evidence that Cdc42EP5 is a regulator of cancer cell motility that coordinates actin and septin networks and describes a unique role for SEPT9 in melanoma invasion and metastasis

Efectividad de los apósitos especiales en el tratamiento de úlceras por presión y vasculares

Esta revisión pretende evaluar la eficacia y la relación coste-eficacia del empleo de apósitos especiales en el tratamiento de las úlceras por presión y úlceras vasculares, tanto venosas como arteriales.Resumen, Objetivo, Métodos, Criterios de inclusión, Resultados, INAHTA Structured Summary, Introducción, Antecedentes históricos El proceso de reparación tisular y curación de las heridas, Fisiología de la cicatrización y curación, Fase de cicatrización, Fase de pitelización, Tipos de cicatrización, Primaria o por primera intención Secundaria o por segunda intención, Factores relacionados con el proceso de curación de una herida, Generales, Locales, Heridas crónicas Características de los procesos contemplados en el presente informe Úlceras por presión, Epidemiología, Etiología, Prevención, Aproximación al tratamiento, Úlceras vasculares, Características epidemiológicas y clínicas, Etiología y diagnóstico, Factores relacionados con la evolución y tratamiento, Objetivo del presente informe, Apósitos especiales para el tratamiento local de las heridas, Tipos de apósitos Convencionales, Especiales, Características que debe reunir un apósito "ideal", Métodos, Criterios de inclusión, Selección de estudios y extracción de datos, Evaluación de la medida resultado, Análisis de la calidad metodológica y de la evidencia científica, Historial de búsqueda, Resultados y discusión, Estudios incluidos, Presentación detallada de los resultados, Análisis metodológico y calidad de los estudios, Análisis de los estudios y de los resultados obtenidos sobre la variable "curación" según la etiología del proceso, Úlceras por presión, Comparación entre apósitos especiales y tratamiento convencional, Comparación entre apósitos especiales, Úlceras vasculares Úlceras venosas, Comparación entre apósitos especiales, Úlceras de etiología mixta arterial y venosa, Resultados no definidos de acuerdo a la etiología de las lesiones, Análisis de los resultados económicos Conclusiones, Bibliografía, Anexo I: Resumen descriptivo de los estudios incluidos, Úlceras por presión, Úlceras vasculares, Úlceras venosas, Úlceras de etiología mixta venosa y arterial, Úlceras venosas, úlceras por presión y otros tipos de heridas: sin diferenciar resultados por etiología, Anexo II: Resumen descriptivo de los estudios que analizan costes, Úlceras por presión, Úlceras vasculares, Úlceras por presión y vasculares, Anexo III: Historial de búsqueda

Ingeniería y Medicina: cuando uno más uno suma más que dos

La historia de los avances médicos está ligada al desarrollo de la ingeniería. No en pocas ocasiones, los avances en el conocimiento científico-médico han ido por delante de lo que la tecnología podía ofrecer y ha sido sólo, después de años de desarrollo, cuando se ha podido implementar el instrumento que satisfacía las necesidades concretas. En este artículo se pone de manifiesto la simbiosis entre la ingeniería y la medicina a lo largo de la historia y se centra en los avances significativos que han ocurrido en tres tecnologías clave en los últimos años: la robótica, las comunicaciones móviles 5G y la inteligencia artificial. Todo ello con aplicación, principalmente, al ámbito de la cirugía por ser, quizás, uno de los ámbitos donde ésta resulta más impactante. Además, se proporcionarán las claves fundamentales para poder entender el impacto actual y futuro de estas tecnologías.The history of medical advances is inevitably linked to the developments achieved in engineering. On many occasions, advances in scientific-medical knowledge have gone ahead of what technology could offer, and it has only been, after years of development, that it has been possible to implement the instrument that satisfies the specific needs. This article highlights the symbiosis between engineering and medicine throughout history and focuses on the significant advances that have occurred in three key technologies in recent years: robotics, 5G mobile communications, and artificial intelligence. All this mainly applied to the field of surgery as it is, perhaps, one of the fields where it is most impressive. In addition, fundamental keys to understand the current and future impact of these technologies will be outlined

A preclinical pipeline to evaluate migrastatics as therapeutic agents in metastatic melanoma

© The Author(s) 2021.[Background]: Metastasis is a hallmark of cancer and responsible for most cancer deaths. Migrastatics were defined as drugs interfering with all modes of cancer cell invasion and thus cancers’ ability to metastasise. First anti-metastatic treatments have recently been approved. [Methods]: We used bioinformatic analyses of publicly available melanoma databases. Experimentally, we performed in vitro target validation (including 2.5D cell morphology analysis and mass spectrometric analysis of RhoA binding partners), developed a new traceable spontaneously metastasising murine melanoma model for in vivo validation, and employed histology (haematoxylin/eosin and phospho-myosin II staining) to confirm drug action in harvested tumour tissues. [Results]: Unbiased and targeted bioinformatic analyses identified the Rho kinase (ROCK)-myosin II pathway and its various components as potentially relevant targets in melanoma. In vitro validation demonstrated redundancy of several RhoGEFs upstream of RhoA and confirmed ROCK as a druggable target downstream of RhoA. The anti-metastatic effects of two ROCK inhibitors were demonstrated through in vivo melanoma metastasis tracking and inhibitor effects also confirmed ex vivo by digital pathology. [Conclusions]: We proposed a migrastatic drug development pipeline. As part of the pipeline, we provide a new traceable spontaneous melanoma metastasis model for in vivo quantification of metastasis and anti-metastatic effects by non-invasive imaging.GOF’s lab was supported by Cancer Research UK [C48390/A21153], Worldwide Cancer Research [16-1153], and King’s Health Partners [King’s Medical Research Trust Joint Research Committee studentship to A.V.]. B.F. was supported by a King’s Health Partners studentship to V.S.M. and G.O.F. V.S.M.’s lab was supported by Cancer Research UK [C33043/A12065] and [C33043/A24478] (V.S.M., E.C.M., J.L.O., L.B. and GC), the Royal Society [RG110591] (V.S.M.), The Harry J. Lloyd Charitable Trust (J.L.O. and V.S.M.), the Barts Charity (V.S.M., J.L.O., O.M., I.R.H. and E.C.M.), the Fundacion Alfonso Martin Escudero and Marie Sklodowska-Curie Action [H2020-MSCA-IF-2014-EF-ST] (I.R.H.), and Fundacion Ramon Areces (E.C.M.). F.M. was supported by an MRC Career Development Award (MR/P009417/1). This work was further supported by the Department of Health (DoH) via the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre award to King’s Health Partners, and the Wellcome/EPSRC Centre for Medical Engineering [WT203148/Z/16/Z]. Views expressed are those of the authors and not necessarily those of the NHS, NIHR or DoH

Efficient inhibition of iron superoxide dismutase and of Trypanosoma cruzi growth by benzo[g]phthalazine derivatives functionalized with one or two imidazole rings

The synthesis and trypanosomatic behavior of a new series of 1,4-bis(alkylamino)benzo[g]phthalazines 1−4 containing the biologically significant imidazole ring are reported. In vitro antiparasitic activity against Trypanosoma cruzi epimastigotes is remarkable, especially for compound 2, whereas toxicity against Vero cells is very low. Conversion of epimastigotes to metacyclic forms in the presence of the tested compounds causes significant decreases in the amastigote and trypomastigote numbers. Fe-SOD inhibition is noteworthy, whereas effect on human Cu/Zn-SOD is negligible.The authors thank the Spanish CICYT for the financial support

Differences between CAFs and their paired NCF from adjacent colonic mucosa reveal functional heterogeneity of CAFs, providing prognostic information

Little is known about the difference in gene expression between carcinoma-associated fibroblasts (CAFs) and paired normal colonic fibroblasts (NCFs) in colorectal cancer. Paired CAFs and NCFs were isolated from eight primary human colorectal carcinoma specimens. In culture conditions, soluble factors secreted by CAFs in the conditioned media increased clonogenicity and migration of epithelial cancer cells lines to a greater extent than did NCF. In vivo, CAFs were more competent as tumour growth enhancers than paired NCFs when co-inoculated with colorectal cell lines. Gene expression analysis of microarrays of CAF and paired NCF populations enabled us to identify 108 deregulated genes (38 upregulated and 70 downregulated genes). Most of those genes are fibroblast-specific. This has been validated in silico in dataset GSE39396 and by qPCR in selected genes. GSEA analysis revealed a differential transcriptomic profile of CAFs, mainly involving the Wnt signallingsignalling pathway, focal adhesion and cell cycle. Both deregulated genes and biological processes involved depicted a considerable degree of overlap with deregulated genes reported in breast, lung, oesophagus and prostate CAFs. These observations suggest that similar transcriptomic programs may be active in the transition from normal fibroblast in adjacent tissues to CAFs, independently of their anatomic demarcation. Additionally NCF already depicted an activated pattern associated with inflammation. The deregulated genes signature score seemed to correlate with CAF tumour promoter abilities in vitro, suggesting a high degree of heterogeneity between CAFs, and it has also prognostic value in two independent datasets. Further characterization of the roles these biomarkers play in cancer will reveal how CAFs provide cancer cells with a suitable microenvironment and may help in the development of new therapeutic targets for cancer treatment

Non-muscle Myosin II reactivation and cytoskeletal remodelling as a new vulnerability in therapy-resistant melanoma

Trabajo presentado en el 3rd ASEICA Educational Symposium, celebrado en modalidad virtual del 23 al 25 de noviembre de 2021.MAPK-targeted therapies (MAPKi) and immune checkpoint blockers (ICB) improve survival of subsets of melanoma patients. However, therapy resistance is a persistent problem. Cross-resistance to MAPKi and ICB may be driven by common transcriptomic alterations in pathways controlling invasion and metastasis. Using phosphoproteomic and transcriptomic analyses, we find that adaptation to treatment and acquisition of resistance to MAPKi involve cytoskeletal remodelling and changes in levels in the ROCK-non-muscle Myosin II (NMII) pathway, which is essential for cancer invasion and metastasis. NMII activity is decreased shortly after MAPK is blocked. However, persister cells promptly restore NMII activity to increase survival, and this becomes a vulnerability, since survival of MAPKi- and ICB-resistant cells is highly dependent on ROCK-NMII. Efficacy of MAPKi and ICB can be improved by combination with ROCK inhibitors, which have a dual action by impairing melanoma cell survival (through induction of lethal reactive oxygen species and unresolved DNA damage) and reducing myeloid- and lymphoid-driven immunosuppression, ultimately overcoming cross-resistance in vivo. In human tumours, high ROCK-NMII levels identify MAPKi-, ICB-resistant melanomas, and treatment-naïve melanomas with worse prognosis. Therefore, a subset of MAPKi- and ICB-resistant melanomas is more susceptible to ROCK-NMII blockade, suggesting clinical opportunities for combination therapies