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

Delay effects in the response of low-grade gliomas to radiotherapy: a mathematical model and its therapeutical implications

Low-grade gliomas (LGGs) are a group of primary brain tumours usually encountered in young patient populations. These tumours represent a difficult challenge because many patients survive a decade or more and may be at a higher risk for treatment-related complications. Specifically, radiation therapy is known to have a relevant effect on survival but in many cases it can be deferred to avoid side effects while maintaining its beneficial effect. However, a subset of LGGs manifests more aggressive clinical behaviour and requires earlier intervention. Moreover, the effectiveness of radiotherapy depends on the tumour characteristics. Recently Pallud et al. (2012. Neuro-Oncology, 14, 1-10) studied patients with LGGs treated with radiation therapy as a first-line therapy and obtained the counterintuitive result that tumours with a fast response to the therapy had a worse prognosis than those responding late. In this paper, we construct a mathematical model describing the basic facts of glioma progression and response to radiotherapy. The model provides also an explanation to the observations of Pallud et al. Using the model, we propose radiation fractionation schemes that might be therapeutically useful by helping to evaluate tumour malignancy while at the same time reducing the toxicity associated to the treatmen

Alteraciones anatómicas y funcionales en la muñeca después de la fractura de la extremidad distal del radio

Se revisaron retrospectivamente 75 casos de fracturas de la extremidad distal del radio tratadas ortopédicamente. Los resultados se valoraron desde el punto de vista anatómico y funcional. En el 49% de los casos existió trazo articular y en el 23% se asoció la lesión de la apó- fisis estiloides del cúbito. Asimismo obtuvimos un 60% de excelentes y buenos resultados a pesar de existir en el 37% de los casos complicaciones evolutivas.A series of 75 cases with fracture of the distal radius treated by conservative methods were retrospectively reciewed. Results were evaluated from anatomical and functional standpoints. In 49% of cases there was an articular extension of the fracture, and 23% had an associated fracture of the ulnar styloid process. Satisfactory outcome was achieved in 60% of cases, although there way 37% of cases showing complications during follow-up

Business computing - A shared curriculum proposal for the spanish-portuguese border under the auspices of the new european higher education area

The Bologna Declaration is leading to a change of paradigm in the context of higher education in many countries of the European Community; it has a significant impact at the level of curriculum and learning models. Therefore, any reflection and decision work on the processes of teaching/learning imposes the curricular reformulation of higher courses in an innovating way, supported by new references and assumptions. In the context of a project financed by European Community program Interreg III A, we have created a workgroup to o propose the reformulation of several courses that belong to Business Computing, from ESTiG-Portugal and from ESPZ-Spain, in an attempt to create harmony between both study plans, considering the socio-economic specific context of the border region between Braganca (Portugal) and Zamora (Spain). This article intends to describe a case-study related to the work done to achieve a curriculum for Business Computing; it describes the changes due to the recent recommendations of Bologna and governmental reflections of Portugal and Spain.This study was partly financed by the European Union with INTERREG III A funds

Cochleates derived from Vibrio cholerae O1 proteoliposomes : The impact of structure transformation on mucosal immunisation

Cochleates are phospholipid-calcium precipitates derived from the interaction of anionic lipid vesicles with divalent cations. Proteoliposomes from bacteria may also be used as a source of negatively charged components, to induce calcium-cochleate formation. In this study, proteoliposomes from V. cholerae O1 (PLc) (sized 160.7±1.6 nm) were transformed into larger (16.3±4.6 µm) cochleate-like structures (named Adjuvant Finlay Cochleate 2, AFCo2) and evaluated by electron microscopy (EM). Measurements from transmission EM (TEM) showed the structures had a similar size to that previously reported using light microscopy, while observations from scanning electron microscopy (SEM) indicated that the structures were multilayered and of cochleate-like formation. The edges of the AFCo2 structures appeared to have spaces that allowed penetration of negative stain or Ovalbumin labeled with Texas Red (OVA-TR) observed by epi-fluorescence microscopy. In addition, freeze fracture electron microscopy confirmed that the AFCo2 structures consisted of multiple overlapping layers, which corresponds to previous descriptions of cochleates. TEM also showed that small vesicles co-existed with the larger cochleate structures, and in vitro treatment with a calcium chelator caused the AFCo2 to unfold and reassemble into small proteoliposome-like structures. Using OVA as a model antigen, we demonstrated the potential loading capacity of a heterologous antigen and in vivo studies showed that with simple admixing and administration via intragastric and intranasal routes AFCo2 provided enhanced adjuvant properties compared with PLc

On the presence of Heterocarpus ensifer Milne Edwards, 1881 (Decapoda, Pandalidae) in the Spanish Mediterranean

Not

Magneto-Optical Activity in High Index Dielectric Nanoantennas

The magneto-optical activity, namely the polarization conversion capabilities of high- index, non-absorbing, core-shell dielectric nanospheres is theoretically analyzed. We show that, in analogy with their plasmonic counterparts, the polarization conversion in resonant dielectric particles is linked to the amount of electromagnetic field probing the magneto-optical material in the system. However, in strong contrast with plasmon nanoparticles, due to the peculiar distribution of the internal fields in resonant dielectric spheres, the magneto-optical response is fully governed by the magnetic (dipolar and quadrupolar) resonances with little effect of the electric ones

La laminoartrectomía en el tratamiento de la estenosis de canal lumbar

Los autores presentan una revisión de 42 pacientes, 33 varones y 9 mujeres, con estenosis del canal lumbar, tratados quirúrgicamente y con un seguimiento medio de 3 años y 8 meses. El tratamiento quirúrgico empleado ha sido la laminoartrectomía a uno o varios niveles, combinada o no con artrodesis. Los mejores resultados se obtuvieron en los pacientes tratados con laminoartrectomía, artrodesis e instrumentación vertebral.The authors present a review of 42 patients, 33 male and 9 female, with lumbar spinal canal stenosis, treated surgically and with a mean follow-up of 3 years-8 months. The surgical treatment was wide laminoarthrectomy involving one o more levels, combined in some cases with spinal fusion. The best results were obtained in patients treated with laminoarthrectomy, arthrodesis and vertebral instrumentation

Fracturas de Astrágalo: Evaluación Clínico-Quirúrgica

Se han revisado 13 pacientes diagnosticados de fractura de astrágalo recogidos en nuestro Servicio de Urgencias y tratados quirúrgicamente en todos los casos. De ellos se ha realizado un seguimiento clínico y radiológico. En el 46% de los casos se obtuvieron resultados satisfactorios (23% excelentes y 23% buenos). Los restantes se repartieron entre regulares (38%) y malos (16%). La necrosis avascular apareció en 3 de los 13 casos, discutiéndose el origen de esta seria complicación. Siguiendo la clasificación de WEBER, los tipos de fractura más frecuentes fueron el tipo III (38%) y el II (31%). La congruencia articular postquirúrgica del astrágalo fracturado y el tiempo de demora en la cirugía que debe ser de urgencia, se muestran como factores a considerar en la evolución ulterior del "Aviators astragalus". Se discute así mismo el valor del signo de Hawkins.Areview of 13 patients diagnosed of Talus fracture has been colected in our service of trauma emergency. All of them have been managed by surgical methods and clinical and radiologically followed up. Satisfactory results wer e obtained in 46% of the cases (23%, excellents and 23%, good results). The rest wer e regular (38%) and bad (16%). Avascular necrosis was observed in 3 of the 13 cases, discussing the origin of this serious complication. The most frequent types of fracture were type III (38%) ant type II (31%) following Weber's classification. The postsurgical articular congruency of the fractured talus and the delayed time on the surgery which must be an emergency, seem to be factors to conside r in the later evolution of the "aviators astragalus". The value of Hawkins sign is also discussed