Search

Cytokine- and chemokine-mediated signalling is involved in the neuroinflammatory process that leads to retinal ganglion cell (RGC) damage in glaucoma. Substances with anti-inflammatory properties could decrease these cytokines and chemokines and thus prevent RGC death. The authors of this study analysed the anti-inflammatory effect of a hydrophilic saffron extract standardized to 3% crocin content, focusing on the regulation of cytokine and chemokine production, in a mouse model of unilateral laser-induced ocular hypertension (OHT). We demonstrated that following saffron treatment, most of the concentration of proinflammatory cytokines (IL-1 beta, IFN-gamma, TNF-alpha, and IL-17), anti-inflammatory cytokines (IL-4 and IL-10), Brain-derived Neurotrophic Factor (BDNF), Vascular Endothelial Growth Factor (VEGF), and fractalkine were unaffected in response to laser-induced OHT in both the OHT eye and its contralateral eye. Only IL-6 levels were significantly increased in the OHT eye one day after laser induction compared with the control group. These results differed from those observed in animals subjected to unilateral OHT and not treated with saffron, where changes in cytokine levels occurred in both eyes. Therefore, saffron extract regulates the production of proinflammatory cytokines, VEGF, and fractalkine induced by increasing intraocular pressure (IOP), protecting the retina from inflammation. These results indicate that saffron could be beneficial in glaucoma by helping to reduce the inflammatory process.

Microalgae and cyanobacteria could play an important role in crop protection, since they produce bioactive substances that promote plant growth and/or trigger the plant resistance mechanisms. The present study focuses on the control of bacterial canker caused by Clavibacter michiganensis subsp. michiganensis on tomato plants by using sonicated extracts from cyanobacteria and microalgae of the genera Leptolyngbya, Nostoc, Chlorella, and Scenedesmus. For the development of this study, 8 strains were firstly tested for their capacity to inhibit the growth of C. michiganensis subsp. michiganensis in vitro, as well as to produce cytokinins and salicylic acid. In order to discard those more phytotoxic strains, the germination index was also estimated in watercress seeds. Scenedesmus-677 and Leptolyngbya-1267 strains were selected in this first phase based on their pesticide and phytostimulant capacity in vitro. Subsequent bioassays on tomato seedlings showed that root application of Scenedesmus-677 could be more aimed at controlling the disease caused by C. michiganensis subsp. michiganensis, while foliar and root application of Leptolyngbya-1267 seems to be more related to the strengthening of the plant through the salicylic acid route. These preliminary results could serve as the basis for a deeper characterization of the biopesticidal and biostimulant effect of both strains, as well as to reveal the benefits derived from the combination of both capacities.

BACKGROUND: Carbohydrate antigen 125 (CA125) and B-type natriuretic peptides are surrogate markers of congestion in patients with acute heart failure (AHF). The aim of the study was to assess the association between CA125 and NT-proBNP and congestion parameters in patients with AHF.; METHODS AND RESULTS: Prospective multicentre observational study that included 191 patients hospitalised for AHF. We recorded the presence of pleural effusion, peripheral oedema and inferior vena cava (IVC) diameter during the first 24-48 hours after admission and evaluated their independent association with CA125 concentrations and the amino-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP). The mean age was 73.4 ± 12 years, 79 (41.4%) were women, and 127 (66.5%) had left ventricular ejection fraction = 50%. The median of CA125, NT-proBNP and IVC diameter was 58 (22.7-129) U/mL, 3,985 (1,905-9,775) pg/mL and 21 (17-25) mm, respectively. Multivariate analysis showed that CA125 was positively and independently associated with the presence of peripheral oedema, pleural effusion and elevated IVC levels. NT-proBNP was associated with pleural effusion and IVC diameter but not with oedema. The addition of CA125 increased the discriminatory capacity of the baseline model to identify peripheral oedema and pleural effusion, but not NT-proBNP. The most important predictor of ICV dilation was CA125 (R2 = 48.3%).; CONCLUSION: In patients with AHF, serum CA125 levels are associated more significantly than NT-proBNP with a state of congestion. Copyright © 2020 Elsevier Espana, S.L.U. All rights reserved.

Trabajo presentado en las II Jornadas RSEF / IFIMED de Física Médica, celebradas en Madrid (España), del 14 al 15 de junio de 2018, In the last decades, proton therapy has gained great interest in the medical community thanks to its excellent clinical results. The bases of this success are: (1) the physical advantages of protons with respect to conventional radiation therapy with photons, due to their more selective energy deposition in depth; and (2) their increased radiobiological effectiveness as compared with photon radiotherapy for a same level of absorbed dose, property usually referred to as Relative Biological Effectiveness or RBE. Even if it is agreed that proton RBE varies towards the distal Bragg peak region, increasing with LET, nowadays in clinical proton therapy treatments, a uniform RBE value of 1.1 is generally used. Therefore, studies of RBE at low proton energies are necessary in order to reach a consensus on the RBE variations near the Bragg peak, which could be significant in the optimization of proton therapy treatment plans. With the purpose of providing a monochromatic beam for RBE measurements at low energies (below 18 MeV in our case), we are preparing an experimental setup at the external beam line of the 18MeV proton cyclotron facility installed at the CNA (Seville, Spain). In this work, we present our first feasibility studies. Two are the main constraints when dealing with the irradiation of biological samples in our setup: low beam intensity, of the order of some pA, to control properly the fluence during irradiation time, and broad irradiation field, of the order of 3cm side, uniform in both energy and space. To improve the homogeneity and decrease the beam intensity, we have decided to use a completely defocused beam and to scatter the beam downstream the exit window, both placing tungsten foils of different thicknesses and changing the amount of air between the window and the position of the samples. So far, we have measured the properties of wide beams produced with tungsten scattering foils of various thicknesses. With a 150 m thick tungsten foil, we could produce a 10 MeV proton beam with almost homogeneous intensity, having deviations of the order of ~10% in the central 35 mm and at ~50 cm distance from the exit window. Furthermore, we have performed preliminary dosimetric studies, using EBT3 radiochromic films and a transmission ionization chamber for dose and proton fluence evaluation. Studies of this nature are of great interest, since radiochromic films would be a handy and easy to use dosimeter solution for proton RBE studies. Finally, we are developing with the Geant4 toolkit a Monte Carlo tool, which reproduces accurately the cyclotron beam properties with the aim of simulating future improvements proposed on the final optimization of the setup for the irradiation of biological samples., This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 675265, OMA - Optimization of Medical Accelerators, and from the Spanish Ministry of Economy and Competitiveness under grant No FPA2016-77689-C2-1-R. The Monte Carlo simulations were carried out at the FIS-ATOM cluster hosted at CICA (Seville, Spain).

Trabajo presentado en el 3rd OMA Topical Workshop on Accelerator Design and Diagnostics, celebrado en Darmstadt (Alemania), del 11 al 18 de diciembre de 2018

Trabajo presentado en 2nd OMA Topical Workshop on Diagnostics for Beam and Patient Monitoring, celebrado en Ginebra (Suiza), del 4 al 5 de junio de 2018

Trabajo presentado en Rábida 2018: International Scientific Meeting on Nuclear Physics, celebrado en La Rábida (Sevilla, España), del 18 al 22 de junio de 2018, In the last decades, particle radiation therapy, mainly performed with protons and carbon ions, has gained great interest in the medical community thanks to its excellent clinical results. The bases of this success are: (1) the physical advantages of protons and heavier ions with respect to conventional radiation therapy with photons, due to their more selective energy deposition in depth; and (2) their increased radiobiological effectiveness, since protons and heavier ions offer a higher cell-killing effectiveness if compared to photons for a same level of absorbed dose, property usually referred to as Relative Biological Effectiveness or RBE. The RBE depends on different factors, both physical and biological, such as radiation quality, track structure, linear energy transfer (LET), tissue type, biological endpoint, etc. However, in the case of protons, there is still place for improvements in what concerns the understanding of the behaviour of the RBE on both cancer and healthy cells, and its role in treatment planning and delivery. Even if it is agreed that proton RBE varies towards the distal Bragg peak region, increasing with LET, nowadays in clinical proton therapy treatments, a uniform RBE value of 1.1 is generally used, leading possibly to suboptimal proton treatment plans, as stated in Wedenberg et al. Therefore, studies of RBE at low proton energies are necessary in order to optimize proton therapy treatment plans and reach a consensus on the RBE variations near the Bragg peak. However, not many proton facilities can provide a monochromatic beam for radiobiological measurements at low energies (roughly below 20 MeV). With this purpose, we are preparing an experimental setup at the external beam line of the 18MeV proton cyclotron facility installed at the CNA (Seville, Spain) to cover this gap. [Methods and Results] In this work, we present our first feasibility studies. At present, the experimental beam line installed at the cyclotron facility counts on two Faraday cups for beam diagnostics, and on two collimators of 1.5 cm diameter placed at 1 m distance one from the other, the second of them mounted together with a 100 µm Aluminium exit window, for beam delivery and shaping. Two are the main constraints when dealing with cell irradiations: low beam intensity, of the order of some pA, to control properly the fluence during irradiation time, and broad irradiation field, of the order of 3cm side, uniform in both energy and space. In order to improve the homogeneity and decrease the beam intensity, we have decided to use a completely defocused beam and to scatter the beam downstream the exit window, both placing tungsten foils of different thicknesses and changing the amount of air between the window and the samples position. So far, we have measured the properties of wide beams produced with tungsten scattering foils of various thicknesses. With a 150 m thick tungsten foil, we could produce a 10 MeV proton beam with almost homogeneous intensity, having deviations of the order of ~10% in the central 35 mm and at ~50 cm distance from the exit window. Furthermore, we have performed preliminary dosimetric studies, using EBT3 radiochromic films and a transmission ionization chamber for dose and proton fluence evaluation. Studies of this nature are of great interest, since radiochromic films would be a handy and easy to use dosimeter solution for proton RBE studies. Finally, we are developing with the Geant4 toolkit a Monte Carlo tool, which reproduces accurately the cyclotron beam properties with the aim of simulating future improvements proposed on the final optimization of the setup for the irradiation of biological samples., This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 675265, OMA Optimization of Medical Accelerators, and from the Spanish Ministry of Economy and Competitiveness under grand No FPA2016-77689-C2-1-R. The Monte Carlo simulations were carried out at the FIS-ATOM cluster hosted at CICA (Seville, Spain).

New experimental results for the elastic scattering of 6He on 64Zn at incident energies of 15.0 and 18.0 MeV and 4He at 17.5 MeV along with results already published at 10.0 and 13.6 MeV, are presented. Elastic and alpha experimental cross sections are compared with coupled-reaction-channel, continuum-discretized coupledchannel, and DWBA inclusive-breakup models. The large yield of alpha particles observed at all measured energies can be explained by considering a nonelastic breakup mechanism.

Navarro-Sigüenza, Adolfo G., Almazán-Núñez, R. Carlos, Sánchez-Ramos, L. Enrique, Rebón-Gallardo, M. Fanny, Arbeláez-Cortés, Enrique (2020): Relict Humid Tropical Forest In Mexico Promotes Differentiation In Barred Woodcreepers (Aves: Furnariidae). Zootaxa 4780 (2): 307-323, DOI: https://doi.org/10.11646/zootaxa.4780.2.5

Background: Recent studies have demonstrated that alcohol consumption can modulate the immune system by directly activating natural immunity and triggering inflammatory processes in the central nervous system and in peripheral organs, such as the liver and pancreas. Patients with alcohol use disorders have an elevated frequency of comorbid mental disorders and gut diseases (i.e. fatty liver and pancreatitis) that complicate diagnosis, treatment and prognosis. Aims: The present study aims to explore possible associations in circulating plasma cytokine concentrations in abstinent patients diagnosed with alcohol use disorders. Methods: To this end, 85 abstinent subjects with alcohol use disorders from an outpatient setting and 55 healthy subjects were evaluated for both substance and mental disorders. The plasma levels of cytokines interleukin 1 beta, interleukin 4, interleukin 6, interleukin 17A, interferon gamma and tumour necrosis alpha were determined and their association with (a) history of alcohol consumption, (b) psychiatric comorbidity and (c) liver/pancreas comorbidities was explored. Results: We found that plasma concentrations of interleukin 1 beta, interleukin 6 and tumour necrosis alpha were increased, whereas plasma concentrations of interleukin 4, interleukin 17A and interferon gamma were decreased in abstinent alcohol use disorder patients as compared with control subjects. Moreover, we found that changes in interleukin 6 and interleukin 17A plasma concentrations in alcohol use disorder patients were associated with the presence of liver and pancreatic diseases. Conclusion: The present results suggest alcohol use disorder is associated with alterations of plasma cytokines, being interleukin 6 and interleukin 17A potential biomarkers of the presence of comorbidities of digestive organs. The clinical relevance of these findings is discussed in the context of alcohol-induced inflammatory processes.

This article belongs to the Special Issue Cells and Materials for Disease Modeling and Regenerative Medicine., Leigh syndrome (LS) is the most frequent infantile mitochondrial disorder (MD) and is characterized by neurodegeneration and astrogliosis in the basal ganglia or the brain stem. At present, there is no cure or treatment for this disease, partly due to scarcity of LS models. Current models generally fail to recapitulate important traits of the disease. Therefore, there is an urgent need to develop new human in vitro models. Establishment of induced pluripotent stem cells (iPSCs) followed by differentiation into neurons is a powerful tool to obtain an in vitro model for LS. Here, we describe the generation and characterization of iPSCs, neural stem cells (NSCs) and iPSC-derived neurons harboring the mtDNA mutation m.13513G>A in heteroplasmy. We have performed mitochondrial characterization, analysis of electrophysiological properties and calcium imaging of LS neurons. Here, we show a clearly compromised oxidative phosphorylation (OXPHOS) function in LS patient neurons. This is also the first report of electrophysiological studies performed on iPSC-derived neurons harboring an mtDNA mutation, which revealed that, in spite of having identical electrical properties, diseased neurons manifested mitochondrial dysfunction together with a diminished calcium buffering capacity. This could lead to an overload of cytoplasmic calcium concentration and the consequent cell death observed in patients. Importantly, our results highlight the importance of calcium homeostasis in LS pathology., This research was funded by ‘Fondo de Investigación Sanitaria, Instituto de Salud Carlos III co-funded by European Regional Development Funds’, grant number PI15/00484 and PI18/00151 to M.E.G; PI13/00556 and PI16/00789 to R.G. F.Z.-D. received grant support from the Ministerio de Educación, Cultura y Deporte (FPU13/00544). M.E.G. is supported by a ‘Miguel Servet’ contract (CP16/00046) from Instituto de Salud Carlos III and European Regional Development Funds. HA received support from the Swedish Research Council.

Infections related to dental implants are a common complication that can ultimately lead to implant failure, and thereby carries significant health and economic costs. In order to ward off these infections, this paper explores the immobilization of triethoxysilylpropyl succinic anhydride (TESPSA, TSP) silane onto dental implants, and the interaction of two distinct monospecies biofilms and an oral plaque with the coated titanium samples. To this end, titanium disks from prior machining were first activated by a NaOH treatment and further functionalized with TESPSA silane. A porous sodium titanate surface was observed by scanning electron microscopy and X-ray photoelectron spectroscopy analyses confirmed the presence of TESPSA on the titanium samples (8.4% for Ti-N-TSP). Furthermore, a lactate dehydrogenase assay concluded that TESPSA did not have a negative effect on the viability of human fibroblasts. Importantly, the in vitro effect of modified surfaces against Streptococcus sanguinis, Lactobacillus salivarius and oral plaque were studied using a viable bacterial adhesion assay. A significant reduction was achieved in all cases but, as expected, with different effectiveness against simple mono-species biofilm (ratio dead/live of 0.4) and complete oral biofilm (ratio dead/live of 0.6). Nevertheless, this approach holds a great potential to provide dental implants with antimicrobial properties.

Background: In our recent experiment, Be9+p at 5.67A MeV, the breakup decay rates to the three configurations, α+α+n, Be∗8+n and He5+He4 of Be9, were observed and quantified in the proton recoil spectra, in a full kinematics approach. Unfolding step by step the accessibility to the above configurations, it will require similar experiments at lower or/and higher energies. It will also require the interpretation of the data in a theoretical framework. Three-body models for the structure of Be9 have been developed and applied to reactions with heavy targets. Further research on lighter targets is required for the best establishment of the model. Such models are relevant for the calculation of the corresponding radiative capture reaction rate, α(α,γ)Be9 followed by Be9(α,n)C12. The last is essential for the r-process abundance predictions. Purpose: Investigate the breakup decay rate of Be9+p at 2.72A MeV, where the direct configuration α+α+n is mainly accessible. Compare and interpret data at this low energy and at the higher energy of 5.67A MeV into a four-body continuum discretized coupled-channel formalism. Point out and discuss couplings to continuum. Methods: Our experimental method includes an exclusive breakup measurement in a full kinematic approach of Be9 incident on a proton target at 24.5 MeV (2.72A MeV). Complementary the elastic scattering is measured and other reaction channels are evaluated from previous measurements under the same experimental conditions. The interpretation of present data at 2.72A MeV and previous data at 5.67A MeV, are considered in a four-body continuum discretized coupled channel (CDCC) approach, using the transformed harmonic oscillator method for the three-body projectile. Results: An elastic scattering angular distribution at 2.72A MeV is measured, which compares very well with CDCC calculations, indicating a strong coupling to continuum. At the same energy, the breakup and total reaction cross sections are measured as σbreak=2.5±1mb and σtot=510±L90mb, in good agreement with the calculated values of 3.7 and 433 mb, respectively. Further on, into the same theoretical framework, the elastic scattering and breakup cross section data at 5.67A MeV are found in very good agreement with the CDCC calculations. Conclusions: It was confirmed in a global experimental framework that four-body CDCC calculations can describe very well the data even at low energies. Coupling to continuum is very strong despite the small measured breakup cross section. Moreover, the present results support further our three-body model for the structure of Be9, validating relevant radiative reaction rates obtained previously. © 2020 American Physical Society.

We report on an attempt to reproduce the observation of beta-minus-delayed proton emission from ¹¹Be through detection of the final state nucleus ¹⁰Be with accelerator mass spectrometry. Twelve samples were collected at the ISOLDE facility at CERN at different separator settings, allowing tests of different sources of contamination to be carried out. The observed amounts of ¹⁰Be per collected ¹¹Be rule out several contamination sources, but do not agree internally. Formation of BeH molecular ions in the ion source may explain our data, in which case an upper limit of the beta p branching ratio of 2.2 x10-6 can be derived.