Hypoxic Cell Waves around Necrotic Cores in Glioblastoma: A Biomathematical Model and its Therapeutic Implications

Glioblastoma is a rapidly evolving high-grade astrocytoma that is distinguished pathologically from lower grade gliomas by the presence of necrosis and microvascular hiperplasia. Necrotic areas are typically surrounded by hypercellular regions known as "pseudopalisades" originated by local tumor vessel occlusions that induce collective cellular migration events. This leads to the formation of waves of tumor cells actively migrating away from central hypoxia. We present a mathematical model that incorporates the interplay among two tumor cell phenotypes, a necrotic core and the oxygen distribution. Our simulations reveal the formation of a traveling wave of tumor cells that reproduces the observed histologic patterns of pseudopalisades. Additional simulations of the model equations show that preventing the collapse of tumor microvessels leads to slower glioma invasion, a fact that might be exploited for therapeutic purposes.Comment: 29 pages, 9 figure

Combined therapies of antithrombotics and antioxidants delay in silico brain tumor progression

Glioblastoma multiforme, the most frequent type of primary brain tumor, is a rapidly evolving and spatially heterogeneous high-grade astrocytoma that presents areas of necrosis, hypercellularity and microvascular hyperplasia. The aberrant vasculature leads to hypoxic areas and results in an increase of the oxidative stress selecting for more invasive tumor cell phenotypes. In our study we assay in silico different therapeutic approaches which combine antithrombotics, antioxidants and standard radiotherapy. To do so, we have developed a biocomputational model of glioblastoma multiforme that incorporates the spatio-temporal interplay among two glioma cell phenotypes corresponding to oxygenated and hypoxic cells, a necrotic core and the local vasculature whose response evolves with tumor progression. Our numerical simulations predict that suitable combinations of antithrombotics and antioxidants may diminish, in a synergetic way, oxidative stress and the subsequent hypoxic response. This novel therapeutical strategy, with potentially low or no toxicity, might reduce tumor invasion and further sensitize glioblastoma multiforme to conventional radiotherapy or other cytotoxic agents, hopefully increasing median patient overall survival time.Comment: 8 figure

Las zonas arqueológicas como paisajes culturales: el parque arqueológico de Las Médulas(León)

Sin resume

Mandibular odontogenic myxoma : reconstructive considerations by means of the vascularized fibular free flap

The odontogenic myxoma is a rare entity located in mandible and upper maxilla. Due to its local aggressiveness, wide surgical excision is mandatory. Several surgical techniques have been described for the reconstruction of segmental mandibular defects. In comparison with other free flaps, the vascularized free fibular flap (VFFF) supports the longest amount of bone and, due to the nature of the vascular supply a complete freedom in location of the osteotomy is present. A precise mandibular arc can be performed following bone resection. We suggest the performance of the ?in situ? VFFF technique in order to recreate mandibular contour by means of several osteotomies, while the pedicle is still attached to the leg. Substantial decrease in surgical time is obtained. With the ?double-barrel? technique and subsequent osseointegrated implants, good results are obtained in the reconstruction of dentate patients without maxillary atrophy. We present two new cases of large odontogenic mandibular myxoma. Wide surgical excision by means of hemimandibulectomies and subsequent reconstruction with VFFF were performed

A comparative study of magnetic and electrical properties of BiFeO3 mutiferroic ceramics sintered by electric field assisted-methods: Spark plasma sintering and flash sintering

Please click Additional Files below to see the full abstract

Obtención de estireno a partir de residuos de poliestireno expandido mediante pirolisis catalítica

En este trabajo se estudió un proceso de pirolisis catalítica que permite transformar los residuos de poliestireno expandido a su monómero de estireno, con la finalidad de ser reutilizado en la industria del poliestireno para la fabricación de nuevos productos y, de esta manera, efectuar su reciclaje. El poliestireno, a diferencia de otros polímeros, tiene un gran potencial para producir su monómero a través de un proceso de pirolisis y es posible aumentar su rendimiento utilizando un catalizador adecuado. Debido a la baja densidad del poliestireno expandido (0.012 g/mL) es necesario reducir su volumen, disolviéndolo en un solvente apropiado. Los criterios para seleccionar el solvente fueron: buena solubilidad del poliestireno, no estar clasificado como tóxico, tener bajo costo y disponibilidad en el mercado. Se realizaron pruebas con diferentes catalizadores básicos para determinar cuál es el que proporciona el mejor rendimiento. Se determinó la cinética de la reacción de pirolisis del poliestireno expandido.In this work it was studied a catalytic pyrolysis process that allows to transform waste expanded polystyrene to its styrene monomer, in order to be reused in the polystyrene industry for the manufacture of new products and, in this way, to carry out its recycling. Polystyrene, unlike other polymers, has great potential to produce its monomer through a pyrolysis process and it is possible to increase its yield using a suitable catalyst. Due to the low density of expanded polystyrene (0.012 g/mL) it is necessary to reduce its volume, dissolving it into an appropriate solvent. The criteria for selecting the solvent were: polystyrene good solubility, not being classified as toxic, having low cost and availability in the market. Tests were performed with different basic catalysts to determine which one provides the best yield. The kinetics of expanded polystyrene pyrolysis reaction were determined

In vitro characterization of solute transport in the spinal canal

This paper presents results of an experimental investigation of solute transport in a simplified model of the spinal canal. The work aims to provide increased understanding of the mechanisms responsible for drug dispersion in intrathecal drug delivery (ITDD) procedures. The model consists of an annular channel bounded externally by a rigid transparent tube of circular section, representing the dura mater, and internally by an eccentric cylindrical compliant insert, representing the spinal cord. The tube, closed at one end, is connected to a rigid acrylic reservoir, representing the cranial cavity. The system is filled with water, whose properties are almost identical to those of the cerebrospinal fluid. A programmable peristaltic pump is employed to generate oscillatory motion at frequencies that are representative of those induced by the cardiac and respiratory cycles. Laser induced fluorescence is used to characterize the dispersion of fluorescent dye along the canal and into the cranial cavity for different values of the relevant Womersley number and different eccentricities of the annular section. The present work corroborates experimentally, for the first time, the existence of a steady bulk flow, associated with the mean Lagrangian motion, which plays a key role in the transport of the solute along the spinal canal. The measurements of solute dispersion are found to be in excellent agreement with theoretical predictions obtained using a simplified transport equation derived earlier on the basis of a two-timescale asymptotic analysis. The experimental results underscore the importance of the eccentricity and its variations along the canal and identifies changes in the flow topology associated with differences in the Womersley number, with potential implications in guiding future designs of ITDD protocols.This work was supported by the coordinated project, PID2020-115961RB-C31, PID2020-115961RB-C32, and PID2020-115961RA-C33, financed by MCIN/AEI/10.13039/501100011033, and by the Junta de Andalucia and European Funds, Project No. P18-FR-4619. F. Moral-Pulido wants to thank the Spanish Ministry of Universities for the financial support provided by the Fellowship FPU18/05694. The work of A. L. Sánchez was supported by the U.S. National Science Foundation through Grant No. 1853954

Endoscopically-assisted transoral approach for the treatment of subcondylar fractures of the mandible

Introduction: Treatment of subcondylar fractures of the mandible is one of the most controversial aspects in the field of maxillofacial traumatology. This controversy centers on the positive and negative aspects of open and closed approaches for the treatment of this kind of fractures. Open techniques lead to good reduction and osteosynthesis, but have a high risk of injury to the facial nerve and produce facial scars. Closed techniques (intermaxillary fixation) reduce all the above-mentioned risks but rarely produce correct anatomic reduction, and complications such as ankylosis, condylar necrosis and inhibition of mandibular growth, causing abnormal occlusion, may occur. Despite all the associated risks, closed techniques are currently the most popular treatment. Objectives: To introduce the endoscopically-assisted transoral approach for the treatment of subcondylar fractures, presenting three cases treated in our department. A description of the technique has been included as well as the clinical and radiographic results obtained. Material and Methods: The study is based in three patients with subcondylar fractures of the mandible who were treated by an endoscopically-assisted transoral approach. A description of the surgical technique is included. The results were assessed by postsurgical radiographic control (orthopantomography), maximum mouth opening, occlusion and pain. Results: Three reductions of subcondylar fractures with transoral endoscopically-assisted approach were undertaken. The follow-up period was 6 months. Postsurgical radiographic control showed good reduction of the fracture in all three cases. None of the patients showed any sign of temporomandibular dysfunction after 6 months. Conclusion: Endoscopic treatment by transoral approach combines the positive aspects of both conventional techniques: closed and open reduction; allowing anatomic reduction and a stable fixation leaving no visible facial scars and with a minimum risk of injury to the facial nerve

An In Silico Approach to Enzymatic Synthesis of Fucooligosaccharides Using α-L-Fucosidase from Thermotoga maritima

Abstract: Fucooligosaccharides comprise the primary group of human milk oligosaccharides. Due to their beneficial properties, a series of synthetic methods have been proposed to obtain them. Enzy- matic methods show great promise, and α-L-fucosidase from Thermotoga maritima has emerged as a powerful catalyst for their production. Nonetheless, the enzyme’s limited substrate scope has de- layed its wider application. The present work aims to compare the relative reactivity of fucose, pNP-fucose, and ethyl-fucose, while also exploring the molecular interactions of these fucosyl-donors with the enzyme through a combination DFT and docking analysis. The HOMO-LUMO band gaps range from −7.14571 to −4.24429 eV, with α/β-pNP-fucose and α-fucose being the three most reactive compounds. Moderate association energies between −6.4 to −5.5 kcal·mol−1 were found in the dock- ing analysis, with α-pNP-fucose and both anomers of ethyl-fucose demonstrating the poorest affinity. In the case of α/β-lactose affinity to the β-fucose/enzyme complex, no significant differ- ences were shown. We conclude that the best fucosyl-donors for transfucosylation are those that maintain an enzyme affinity and reactivity similar to pNP-fucose