Neuropathological events in an animal model resembling human fetal post-hemorrhagic hydrocephalus

Introduction: In premature newborns, intraventricular hemorrhages (IVH) probably trigger the disruption of the neurogenic ventricular zone. Most of the cases with severe IVH develop post-hemorrhagic hydrocephalus (PHH). A mouse model with IVH has been developed to research into the common neuropathological events present in PHH and into possible therapies. Methods: In two-day-old mice, the blood serum from littermates was injected into the ganglionic eminence of one hemisphere or both hemispheres. Fourteen days later, a histopathological analysis was carried out. In the case of injection in one hemisphere, the effects were compared with the contralateral non-injected hemisphere. Results: Mice with IVH developed the following neuropathological effects. The ependyma was found denuded and replaced by reactive astrocytes. A reaction of astrocytes over-expressing aquaporin-4 and of NG2 cells was also found developed in the white matter. Alterations in the neurogenesis were also common in the ventricular zone and in the white matter. Conclusions: The animal model of IVH developed shows similar neuropathological events to other forms of congenital hydrocephalus and can be used to research into therapies for PHH.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. PI15/0619 (ISCIII/FEDER) to AJJ

Pre-fatigue influence on quasi-static tensile properties of Ti-6Al-4V in thin-sheet form

The response of engineering structures to loads is most often assessed without taking possible damage of the used material(s) into account. However, it has already been proved that a preceding cyclic loading and the alteration of the microstructure it causes, can have a significant influence on the mechanical properties of steel grades and aluminium alloys , and hence on the behaviour of structural elements made of it. Ti-6Al- 4V, the most widely used titanium alloy, is often one of the materials chosen for cyclic loading applications where other solicitations are present too. Therefore, the influence of pre-fatigue on the quasi-static mechanical properties of Ti-6Al-4V in thin-sheet form is investigated. Tensile experiments are performed on samples subjected to different damage levels. The material does not show a clear dependence of its tensile properties with previous loading cycles, although the overall effect can be important for particular geometries

IPSC differentiation into ependymal progenitors to treat ventricular damage during hydrocephalus

Introduction: During both obstructive congenital hydrocephalus and post-hemorrhagic hydrocephalus additional pathological events are intimately associated with their ethiology: a) a detrimental inflammatory response; b) severe damage of the underlying periventricular nervous tissue, including white matter, and c). Therapeutic approaches have been directed to overcome a) and b), however recovery of damaged neuroepithelium/ependyma is, in our present, an important therapeutic gap. Methods: Human and mouse induced pluripotent stem cells (iPSC) have been artificially differented into ependymal progenitors. Intracerebroventricular (ICV) injections of iPCS are performed ex vivo and in vivo in the damaged ventricular wall. Their integration and differentiation has been studied by immunohistochemistry and histopathological analysis. Results: Mice and human ependymal progenitors are able to integrate and differentiate into ependyma in damaged ventricular wall. Stage of ependymal differentiation by the time of the injection defined different degrees of integration. Conclusions: IPSC appear to be a good ependymal progenitor source with no ethical controversy associated.RyC 2014-16980 Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Experimental and numerical prediction of the static and dynamic forming properties of Ti6Al4V

The strain rate dependence of the plastic yield and failure properties displayed by most metals affects energies, forces and forming limits involved in high speed forming processes. In this contribution a technique is presented to assess the influence of the strain rate on the forming properties of Ti6Al4V sheet. In a first step, static and dynamic tensile experiments are carried out using a classical tensile test device and a split Hopkinson tensile bar facility respectively. Next to uniaxial tensile, also purpose-developed plain strain and shear stress samples are tested. The experimental results clearly show that the mechanical behaviour of Ti6Al4V is strain rate dependent. Indeed, with increasing strain rate, plastic stress levels increase, however, this occurs at the expense of the deformation capacity. Subsequently, to allow simulation of forming processes, Johnson-Cook, Swift and Voce material model parameters are determined. Finally, the influence of the strain rate on the forming limits is assessed using the uni-axial tensile test results. Prediction of the initiation of necking in the Ti6Al4V sheets subjected to multi-axial strain states is based on the Marciniak-Kuczynski model. The thus obtained forming limit diagrams (FLDs) show a non-negligible effect of the strain rate. The reduced ductility at higher strain rates is reflected into an unfavourable downward shift of the FLD. Compared with the experimental data, the static FLD is clearly conservative

Experimental and numerical prediction of the static and dynamic forming properties of Ti6Al4V

The strain rate dependence of the plastic yield and failure properties displayed by most metals affects energies, forces and forming limits involved in high speed forming processes. In this contribution a technique is presented to assess the influence of the strain rate on the forming properties of Ti6Al4V sheet. In a first step, static and dynamic tensile experiments are carried out using a classical tensile test device and a split Hopkinson tensile bar facility respectively. Next to uniaxial tensile, also purpose-developed plain strain and shear stress samples are tested. The experimental results clearly show that the mechanical behaviour of Ti6Al4V is strain rate dependent. Indeed, with increasing strain rate, plastic stress levels increase, however, this occurs at the expense of the deformation capacity. Subsequently, to allow simulation of forming processes, Johnson-Cook, Swift and Voce material model parameters are determined. Finally, the influence of the strain rate on the forming limits is assessed using the uni-axial tensile test results. Prediction of the initiation of necking in the Ti6Al4V sheets subjected to multi-axial strain states is based on the Marciniak-Kuczynski model. The thus obtained forming limit diagrams (FLDs) show a non-negligible effect of the strain rate. The reduced ductility at higher strain rates is reflected into an unfavourable downward shift of the FLD. Compared with the experimental data, the static FLD is clearly conservative

Deformable Nanovesicles Synthesized through an Adaptable Microfluidic Platform for Enhanced Localized Transdermal Drug Delivery.

Phospholipid-based deformable nanovesicles (DNVs) that have flexibility in shape offer an adaptable and facile method to encapsulate diverse classes of therapeutics and facilitate localized transdermal delivery while minimizing systemic exposure. Here we report the use of a microfluidic reactor for the synthesis of DNVs and show that alteration of input parameters such as flow speeds as well as molar and flow rate ratios increases entrapment efficiency of drugs and allows fine-tuning of DNV size, elasticity, and surface charge. To determine the ability of DNV-encapsulated drug to be delivered transdermally to a local site, we synthesized, characterized, and tested DNVs carrying the fluorescently labeled hydrophilic bisphosphonate drug AF-647 zoledronate (AF647-Zol). AF647-Zol DNVs were lyophilized, resuspended, and applied topically as a paste to the calvarial skin of mice. High-resolution fluorescent imaging and confocal microscopy revealed significant increase of encapsulated payload delivery to the target tissue-cranial bone-by DNVs as compared to nondeformable nanovesicles (NVs) or aqueous drug solutions. Interestingly, NV delivery was not superior to aqueous drug solution. Our studies show that microfluidic reactor-synthesized DNVs can be produced in good yield, with high encapsulation efficiency, reproducibility, and stability after storage, and represent a useful vehicle for localized transdermal drug delivery

Sustentabilidad organizacional en Pymes familiares restauranteras de La Jonquera en Cataluña, España

El rol de las pequeñas y medianas empresas (Pymes) familiares en la economía de un país indica la importancia para ellas de ser organizacionalmente susten-tables. En el presente artículo se identifican las manifestaciones de sustentabili-dad organizacional en la capacidad del líder, como principal stakeholder, para la generación de recursos. Se realizó un estudio con trece Pymes familiares restauranteras en la ciudad de La Jonquera, Cataluña, por medio de un cues-tionario aplicado a 50 stakeholders y 9 entrevistas a profundidad con líderes de dichas empresas. Los resultados muestran que la sustentabilidad organiza-cional se encuentra manifiesta en el pensamiento de los stakeholders mediante el análisis cuantitativo de la prueba ANOVA, así como también en el análisis cualitativo de las entrevistas a profundidad. Estos hallazgos pueden ser de uti-lidad para los empresarios, al constatar la necesidad de generar recursos en la empresa para alcanzar su sustentabilidad organizacional

Invariant tori in the lunar problem

Theorems on the existence of invariant KAM tori are established for perturbations of Hamiltonian systems which are circle bundle ows. By averaging the perturbation over the bundle ow one obtains a Hamiltonian system on the orbit (quotient) space by a classical theorem of Reeb. A non-degenerate critical point of the system on the orbit space gives rise to a family of periodic solutions of the perturbed system. Conditions on the critical points are given which insure KAM tori for the perturbed ow. These general theorems are used to show that the near circular periodic solutions of the planar lunar problem are orbitally stable and are surrounded by KAM 2-tori. For the spatial case it is shown that there are periodic solutions of two types, either near circular equatorial, that is, the infinitesimal particle moves close to the plane of the primaries following near circular trajectories and the other family where the ifinitesimal particle moves along the axis perpendicular to the plane of the primaries following near rectilinear trajectories. We prove that the two solutions are elliptic and are surrounded by invariant 3-tori applying a recent theorem of Han, Li, and Yi. In the spatial case a second averaging is performed, and the corresponding or- bit space (called the twice-reduced space) is constructed. The flow of the averaged Hamiltonian on it is given and several families of invariant 3-tori are determined using Han, Li, and Yi Theorem

Long-time effects of an experimental therapy with mesenchymal stem cells in congenital hydrocephalus

Introduction: Bone marrow-derived mesenchymal stem cells (BM-MSC) are a potential therapeutic tool due to their ability for migrating and producing neuroprotector factors when they are transplanted in other neurodegenerative diseases. Moreover, some investigations have shown that BM-MSC are able to modulate astrocyte activation and neuroprotector factor production. The aim of this study was to evaluate the long-time effects of a BM-MSC experimental therapy in the hyh mouse model of congenital hydrocephalus. Methods: BM-MSC were characterized in vitro and then transplanted into the ventricles of young hydrocephalic hyh mice, before they develop the severe hydrocephalus. Non-hydrocephalic normal mice (wt) and hydrocephalic hyh mice sham-injected (sterile saline serum) were used as controls. Samples were studied by analyzing and comparing mRNA, protein level expressions and immunoreaction related with the progression and severity of hydrocephalus. Results: Fourteen days after transplantation, hydrocephalic hyh mice with BM-MSC showed lower ventriculomegaly. In these animals, BM-MSC were found undifferentiated and spread into the periventricular astrocyte reaction. There, BM-MSC were detected producing several neuroprotector factors (BDNF, GDNF, NGF, VEGF), in the same way as reactive astrocytes. Total neocortical levels of NGF, TGF-β and VEGF were found increased in hydrocephalic hyh mice transplanted with BM-MSC. Furthermore, astrocytes showed increased expressions of aquaporin-4 (water channel protein) and Slit-2 (neuroprotective and anti-inflammatory molecule). Conclusions: BM-MSC seem to lead to recovery of the severe neurodegenerative conditions associated to congenital hydrocephalus mediated by reactive astrocytes.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. PI15/0619 (ISCIII/FEDER

Between the Possible and the Not Possible: Interdisciplinarity in Teacher Training

This article presents the obstacles and possibilities for the realization of interdisciplinarity from the perspective of a group of teachers from Teacher Training degree course Data collection was carried out by a form that could be filled on Google Form 2018 2019 and on links sent via email and Whats App Based on the content analysis proposed in Bardin 1997 the data were analyzed based on the context and significance units identified by the authors from the bibliographic study that accompanied the research highlighted in Fazenda 1994 2002 2008 2011 Morin 2000 2003 2006 and Ramos 2004 2016 The results revealed the major obstacles to be of epistemological instructional psychosociological and cultural natur