Lack of Benefit of Extending Temozolomide Treatment in Patients with High Vascular Glioblastoma with Methylated MGMT

[EN] Despite the complete treatment with surgery, chemotherapy and radiotherapy, patients with glioblastoma have a devasting prognosis. Although the role of extending temozolomide treatment has been explored, the results are inconclusive. Recent evidence suggested that tumor vascularity may be a modulating factor in combination with methylation of O6-methylguanine-DNA methyltransferase (MGMT) promotor gene on the effect of temozolomide-based therapies, opening new possibilities for personalized treatments. Before proposing a prospective interventional clinical study, it is necessary to confirm the beneficial effect of the combined effect of MGMT methylation and moderate tumor vascularity, as well as the lack of benefit of temozolomide in patients with a highly vascular tumor.In this study, we evaluated the benefit on survival of the combination of methylation of O6-methylguanine-DNA methyltransferase (MGMT) promotor gene and moderate vascularity in glioblastoma using a retrospective dataset of 123 patients from a multicenter cohort. MRI processing and calculation of relative cerebral blood volume (rCBV), used to define moderate- and high-vascular groups, were performed with the automatic ONCOhabitats method. We assessed the previously proposed rCBV threshold (10.7) and the new calculated ones (9.1 and 9.8) to analyze the association with survival for different populations according to vascularity and MGMT methylation status. We found that patients included in the moderate-vascular group had longer survival when MGMT is methylated (significant median survival difference of 174 days, p = 0.0129*). However, we did not find significant differences depending on the MGMT methylation status for the high-vascular group (p = 0.9119). In addition, we investigated the combined correlation of MGMT methylation status and rCBV with the prognostic effect of the number of temozolomide cycles, and only significant results were found for the moderate-vascular group. In conclusion, there is a lack of benefit of extending temozolomide treatment for patients with high vascular glioblastomas, even presenting MGMT methylation. Preliminary results suggest that patients with moderate vascularity and methylated MGMT glioblastomas would benefit more from prolonged adjuvant chemotherapy.M.A-T was supported by DPI2016-80054-R (Programa Estatal de Promocion del Talento y su Empleabilidad en I+D+i). This work was partially supported by the ALBATROSS project (National Plan for Scientific and Technical Research and Innovation 2017-2020, No. PID2019-104978RB-I00). This study was partially funded by the Fundacio La Marato TV3 (665/C/2013) (http://www.ccma.cat/tv3/marato/projectes-financats/2012/231/ Accessed on 8th September 2021). (JMGG); H2020-SC1-2016-CNECT Project (No. 727560) (JMGG), and H2020-SC1-BHC-2018-2020 (No. 825750) (JMGG). EFG was supported by the European Unions Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 844646 and South-Eastern Norway Regional Health Authority Grant 2021057.Álvarez-Torres, MDM.; Fuster García, E.; Balaña, C.; Puig, J.; Garcia-Gomez, JM. (2021). Lack of Benefit of Extending Temozolomide Treatment in Patients with High Vascular Glioblastoma with Methylated MGMT. Cancers. 13(21):1-14. https://doi.org/10.3390/cancers13215420S114132

Electrochemical and bioelectrocatalytical properties of novel block-copolymers containing interacting ferrocenyl units

The electrochemical characterization of three different polystyrene-b-polybutadiene block copolymers functionalized with ferrocenyl units electronically communicated, PSm-PBn(HSiMeFc2)p where m=615, n=53, p=39 (1), m=375, n=92, p=76 (2) and m=455, n=204, p=170 (3), has been carried out both in solution and electrochemically deposited onto platinum electrodes. The bioelectrocatalytical properties of electrodes modified with the polymers in the nicotinamide dinucleotide (NADH) and glucose oxidase (GOx) oxidations have been investigated as a function of the constitution and structure of the polymers. The analytical properties of electrodes modified with these polymers as sensors of NADH and GOx are described. In addition, an amperometric biosensor for glucose, prepared by electrostatic immobilization of glucose oxidase onto a platinum electrode modified with one of the ferrocenyl block copolymers as an example, has been developed. The results confirm that electrodes modified with the examined copolymers act as efficient redox mediators for the electrocatalytic oxidation of both reduced nicotinamide dinucleotide cofactor and glucose oxidase. The reaction with NADH proceeds via formation of a charge-transfer intermediate before yielding the reaction products. This is a novel example of electrodes modified with ferrocene derivatives that can be applied to the determination of NADH without the use of diaphorase. The redox copolymers co-immobilized with glucose-oxidase have been successfully used as amperometric biosensors for glucose determinations. As expected these compounds allow using lower working potentials. The sensitivities and detection limits obtained are comparable or even better than those of other ferrocene-modified polymers mediator electrodes

La crisis mundial del sector salud y la respuesta Colombiana

En la última década viene creciendo la preocupación mundial por el tema de la salud. su impacto sobre el desarrollo de las naciones, su ñnancíacíón y la eficiencia en su funcionamiento. Es así como las diferentes autoridades económicas del mundo comenzaron a cuestionar los sistemas de ñnanctamíento y el funcionamiento de los sectores de prestación de servicios de salud en todo el orbe por su tendencia ínflacíonarta. su ineficiencia económica y el poco impacto que la mayoría de ellos lograban sobre el estado de salud de la población

Partitioning of trace elements in a entrained flow IGCC plant: Influence of selected operational conditions

The partitioning of trace elements and the influence of the feed conditions (50:50 coal/pet-coke feed blend and limestone addition) was investigated in this study. To this end feed fuel, fly ash and slag samples were collected under different operational conditions at the 335 MW Puertollano IGCC power plant (Spain) and subsequently analysed. The partitioning of elements in this IGCC plant may be summarised as follows: (a) high volatile elements (70–>99% in gas phase): Hg, Br, I, Cl and S; (b) moderately volatile elements (up to 40% in gas phase and 60% in fly ash): As, Sb, Se, B, F, Cd, Tl, Zn and Sn; (c) elements with high condensation potential: (>90% in fly ash): Pb, Ge, Ga and Bi; (d) elements enriched similarly in fly ash and slag 30–60% in fly ash: Cu, W, (P), Mo, Ni and Na; and (e) low volatile elements (>70% in slag): Cs, Rb, Co, K, Cr, V, Nb, Be, Hf, Ta, Fe, U, Ti, Al, Si, Y, Sr, Th, Zr, Mg, Ba, Mn, REEs, Ca and Li. The volatility of As, Sb, and Tl and the slagging of S, B, Cl, Cd and low volatile elements are highly influenced by the fuel geochemistry and limestone dosages, respectively

Multidisciplinary exercises: coordination practices and applications from fundamental to applied subjects in agriculture engineering

This activity is carried out in the framework of an innovation project, whose main objective is to coordinate mathematical, physical and engineering contents for a transversal educational path focused on mechatronics, automated control and information and communication technologies. In such sense one important task in this project is the elaboration of practices and joint applications which will be proposed to the students in successive matters upon different points of view: “Common Practices”. Through this activity students will be guided to establish relationships between their scientific basic training and their technological formation. The students will work on the same example during different academic years and semesters using common materials and working spaces. The whole experience will be displayed in Moodle, a virtual learning environment. A preliminary proposal of “Common practice” is presented in this paper as one example: “Design and Analysis of Suspensions Systems for Stabilizing the Roll of Spray Booms”. In this example students of different academic levels are asked to solve the complexity of the problem along different subjects: Field measurements (analysis of variability on chemical applications using a spray boom) will be realized in the Agriculture Machinery topic - equivalent to 4.5 ECTS -. Analytical models for the analysis of different suspension systems in the Mechanics and Mechanisms topic -4.5 ECTS -. In Agriculture Applied Electronics – 2.5 ECTS – sensors and actuators will be studied to design controllers. Control strategies for damping the resonance frequency of the suspension will be studied in Process Simulation and Optimization – 3.5 ECTS –. And, finally, the design and development of a vehicle with a spray bar and the corresponding suspension systems will be done in the Robotics topic – 7 ECTS –

Diet Supplementation with Polyphenol-Rich Salicornia ramosissima Extracts Protects against Tissue Damage in Experimental Models of Cerebral Ischemia

Salicornia; Ischemia; NeuroprotectionSalicornia; Isquemia; NeuroprotecciónSalicornia; Isquèmia; NeuroproteccióStrokes are the second most common cause of death worldwide and a leading cause of disability. Regular consumption of polyphenols has been shown to reduce the risk of suffering a cardiovascular event. For this reason, we have investigated the protective effect of Salicornia ramosissima, a seasonal halophyte that synthetizes high amounts of bioactive compounds, including polyphenols, in response to environmental stress. Aqueous, hydroalcoholic, and ethanolic extracts were prepared to investigate if dietary supplementation prior to ischemic challenge can prevent subsequent damage using two animal models. First, we screened the protective effect against hypoxia–reoxygenation in Drosophila melanogaster and observed that both ethanolic and hydroalcoholic extracts protected flies from the deleterious effects of hypoxia. Second, we confirmed the protective effect of S. ramosissima ethanolic extract against brain ischemia using the transient middle cerebral artery occlusion mice model. Four weeks of oral supplementation with the ethanolic extract before artery occlusion reduced infarct volume and lowered the plasma levels of the DNA peroxidant product 8-hydroxydeoxyguanosine. Phytochemical profiling of S. ramosissima ethanolic extract revealed 50 compounds. Thus, it represents a valuable source of bioactive compounds that show promising disease-modifying activities and could be further developed as an effective food supplement for the prevention or treatment of neurovascular disorders.The authors received financial support from “CSF-Proyectos estratégicos de I+D+i. Proyectos cofinanciados en un 80% por fondos del Programa Operativo FEDER de Andalucía 2014–2020”, grant number PE-0527-2019. This research was partially funded by “Consejería de Transformación Económica, Industria, Conocimiento y Universidades (CTEICU) y 80% cofinanciados por la UE, PO FEDER Andalucía 2014-2020”, grant number [PY20_01351]. C.d.R. received financial support from the Sara Borrell program funded by ISCIII, grant number [CD21/00148]

Gilthead seabream (Sparus aurata) Mx proteins show positive and negative synergy in their antiviral activity

Due to their direct antiviral activity, Mx proteins play a main role in the response mediated by the type I interferon against viral infections. The study of the farmed fish gilthead seabream Mx genes is specially interesting, since this species displays an unusually high natural resistance to viral diseases, becoming a potential asymptomatic carrier and/or reservoir for several viruses pathogenic to other fish species. Gilthead seabream has three Mx proteins (Mx1, Mx2 and Mx3) that, separately, display antiviral activity against a wide range of viruses, showing interesting differences in their antiviral specificities. In this work, the possible synergy between the three Mx isoforms has been studied using in vitro systems, consisting of permanently transfected CHSE-214 cells expressing two or the three gilthead seabream Mx proteins. The antiviral activity of these Mx combinations has been tested against the infection by the Infectious Pancreatic Necrosis Virus (IPNV), the Viral Haemorrhagic Septicaemia Virus (VHSV) and the European Sheatfish Virus (ESV) in cells inoculated at 0.1 and 0.01 multiplicity of infection (MOI). The antiviral effect was evaluated by viral titration (TCID50 method). Interestingly, a positive synergistic effect in the antiviral activity against ESV was observed when Mx2 and Mx3 were combined, and this effect was intensified when the three isoforms were present in these cells. In contrast, the presence of more than one Mx isoform interfered with the antiviral activity against IPNV and VHSV showed by the Mx proteins expressed separately. Furthermore, Mx2 combined with Mx3, and the combination of the three Mx proteins exerted a negative synergistic effect against IPNV infection. Specifically, the viral titres were significantly higher in Mx expressing cells than in control cells. In the same way, in Mx1 and Mx2 expressing cells infected with VHSV the viral replication was alsoincreased. These results suggest the interaction between Mx isoforms, in which the expression level of each isoform might be an important factor, and support the idea of finely tuned mechanisms controlling the antiviral activity of Mx proteins. The authors want to thank Dr. C. P. Dopazo (University of Santiago de Compostela, Spain) and Dr. K. Way (CEFAS, Weymouth lab, UK) for supplying the viruses VHSV and ESV, respectively, used in this work.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

In Utero p,p′-DDE Exposure and Infant Neurodevelopment: A Perinatal Cohort in Mexico

BACKGROUND: Evidence suggests that p,p′-dichlorodiphenyldichloroethene (DDE) affects neurodevelopment in infants, although a critical exposure window has not yet been identified. OBJECTIVES: Our goal was to assess the prenatal DDE exposure window and its effect on the psychomotor development index (PDI) and mental development index (MDI) during the first year of life. METHODS: We recruited 244 children whose pregnancies and deliveries were uncomplicated, and whose mothers were monitored throughout the pregnancy. Participating mothers were not occupationally exposed to DDT (dichlorodiphenyltrichloroethane) but were residents of a zone in Mexico with endemic malaria. We measured serum levels of DDE before pregnancy and during each trimester of the pregnancy. We evaluated PDI and MDI of the Bayley Scales for Infant Development (BSID-II), at 1, 3, 6, and 12 months of age. We adjusted for quality of the home environment and maternal intellectual coefficient (IQ). We used generalized mixed-effects models for statistical analysis. RESULTS: Third-trimester DDE level (7.8 ± 2.8 ppb) was significantly higher than the level at baseline, first, and second trimesters, but the differences never exceeded 20%. Only DDE levels during the first trimester of pregnancy were associated with a significant reduction in PDI (every doubled increase of DDE level reduced the PDI 0.5 points). DDE was not associated with MDI. CONCLUSIONS: A critical window of exposure to DDE in utero may be the first trimester of the pregnancy, and psychomotor development is a target of this compound. Residues of DDT metabolites may present a risk of developmental delay for years after termination of DDT use

GPR and ERT detection and characterization of a mass burial, Spanish Civil War, Northern Spain

Around 27,000 people were killed in the province of Asturias during the Spanish Civil War, with several thousands killed after the war ended. There are currently over 2,000 known mass burial locations throughout Spain, but many more are unknown. Geophysics is a useful tool employed to help in the active attempts to document and improve knowledge about victims from this conflict. This paper details a non-invasive study of the Cementerio de El Salvador, in the city of Oviedo, Northern Spain. Part of the cemetery contains a known mass burial with approximately 1,300 individuals from the Spanish Civil War and post-war repression eras. Multi-frequency near-surface geophysical techniques were undertaken, after permission, to enhance knowledge about which, if any, techniques should be used to detect, delineate and analyse such mass graves. Multi-frequency (250 MHz and 500 MHz) ground-penetrating radar surveys were acquired together with 2D and 3D Electrical Resistivity Tomography datasets. The results have established the limits of the mass grave and improve the knowledge of the internal mass grave structure. The paper also shows the importance of considering the climatic conditions during data acquisition. This has important implications for the successful detection of recent historical mass burials using near-surface geophysics

Identification of novel targets in adipose tissue involved in non-alcoholic fatty liver disease progression

Obesity is a major risk factor for the development of Nonalcoholic fatty liver disease (NAFLD). We hypothesize that a dysfunctional subcutaneous white adipose tissue (scWAT) may lead to an accumulation of ectopic fat in the liver. Our aim was to investigate the molecular mechanisms involved in the causative role of scWAT in NALFD progression. We performed a RNA-sequencing analysis in a discovery cohort (n = 45) to identify genes in scWAT correlated with fatty liver index, a qualitative marker of liver steatosis. We then validated those targets in a second cohort (n = 47) of obese patients who had liver biopsies available. Finally, we obtained scWAT mesenchymal stem cells (MSCs) from 13 obese patients at different stages of NAFLD and established in vitro models of human MSC (hMSC)-derived adipocytes. We observed impaired adipogenesis in hMSC-derived adipocytes as liver steatosis increased, suggesting that an impaired adipogenic capacity is a critical event in the development of NAFLD. Four genes showed a differential expression pattern in both scWAT and hMSC-derived adipocytes, where their expression paralleled steatosis degree: SOCS3, DUSP1, SIK1, and GADD45B. We propose these genes as key players in NAFLD progression. They could eventually constitute potential new targets for future therapies against liver steatosis