Complicaciones neurológicas asociadas a alteraciones hemostáticas en perros críticamente enfermos : a propósito de 4 casos clínicos

El objetivo de este trabajo es describir las complicaciones neurológicas inusuales en el paciente crítico, secundarias a la presencia de alteraciones hemostáticas. Los casos estudiados fueron seleccionados a partir de perros atendidos en el Hospital Clínico Veterinario durante un periodo de 6 meses. Los pacientes estudiados fueron incluidos en base a los siguientes criterios: presencia de trastornos hemostáticos basados en los resultados del hemograma y las pruebas de coagulación; presencia de complicaciones neurológicas secundarias documentadas en signos clínicos; hallazgos de exploración, necropsia u otros exámenes complementarios. Cuatro perros cumplieron los criterios de inclusión, mientras que uno de ellos fue referido para evaluación neurológica. Los casos restantes desarrollaron signos neurológicos en la UCI. Tres de los pacientes evaluados presentaron complicaciones neurológicas asociadas a sangrado, mientras que el cuarto presentaba signos clínicos asociados a la presencia de trombosis arterial. Tres pacientes,o bien murieron, o fueron eutanasiados debido al desarrollo de complicaciones o al pronóstico desfavorable, mientras que la evolución en el perro superviviente, con un cuadro neurológico multifocal secundario a CID, fue excelente. El examen post mórtem-mortem realizado en 2 / 3 pacientes, confirmó la presencia de hemorragias, trombos de fibrina y lesiones por isquemia en el SNC. Según estas observaciones, la posible existencia de alteraciones en la coagulación debe ser tenida en cuenta cuando el paciente críticamente enfermo desarrolla complicaciones neurológicas de forma aguda. Dado que existe una elevada variabilidad por lo que hace referencia a las alteraciones analíticas detectables en los perfiles analíticos habituales y el estado real del sistema hemostático en el paciente crítico, la evaluación precoz y completa del estatus hemostático del paciente, así como el tratamiento de la enfermedad subyacente, son esenciales para poder anticipar este tipo de complicaciones

The emerging landscape of reimbursement of regenerative medicine products in the UK: publications, policies and politics

Aims This paper aims to map the trends and analyse key institutional dynamics that are constituting the policies for reimbursement of Regenerative Medicine (RM), especially in the UK. Materials & Methods Two quantitative publications studies using Google Scholar and a qualitative study based on a larger study of 43 semi- structured interviews. Results Reimbursement has been a growing topic of publications specific to RM and independent from orphan drugs. Risk- sharing schemes receive attention amongst others for dealing with RM reimbursement. Trade organisations have been especially involved on RM reimbursement issues and have proposed solutions. Conclusion The policy and institutional landscape of reimbursement studies in RM is a highly variegated and conflictual one and in its infancy

Utility of international normative 20 m shuttle run values for identifying youth at increased cardiometabolic risk

The purpose of this study was to examine the ability of international normative centiles for the 20 m shuttle run test (20mSRT) to identify youth at increased cardiometabolic risk. This was a cross-sectional study involving 961 children aged 10–17 years (53% girls) from the United Kingdom. Receiver operating characteristic (ROC) curves determined the discriminatory ability of cardiorespiratory fitness percentiles for predicting increased cardiometabolic risk. ROC analysis demonstrated a significant but poor discriminatory accuracy of cardiorespiratory fitness in identifying low/high cardiometabolic risk in girls (AUC = 0.58, 95% CI: 0.54–0.63; p = 0.04), and in boys (AUC = 0.59, 95% CI: 0.54–0.63; p = 0.03). The cardiorespiratory fitness cut-off associated with high cardiometabolic risk was the 55th percentile (sensitivity = 33.3%; specificity = 84.5%) in girls and the 60th percentile (sensitivity = 42.9%; specificity = 73.6%) in boys. These 20mSRT percentile thresholds can be used to identify children and adolescents who may benefit from lifestyle intervention. Nonetheless, further work involving different populations and cardiometabolic risk scores comprising of different variables are needed to confirm our initial findings

Domestic Care Work: Problems and Requests Emerging from the ‘Triangle of Care’

In Italy, like in many post-industrial societies, eldercare has gone through a profound transformation. Today, the elderly are increasingly assisted in their homes by external workers, who often hail from abroad. Many scholars tend to see this eldercare arrangement, also named ‘migrant-in-the-family model’, as intrinsically inegalitarian. Within this context, we look at three intertwining questions: the disposition toward alternative forms of eldercare; the main issues emerging within the ‘migrant-in-the-family’ model; and the possibility of revising the eldercare model. To address these questions, we built on an archive of in-depth interviews within the so-called ‘triangle of care’ – care managers, the elderly care recipients, and migrant domestic eldercare workers. Our findings reveal that the elderly home care, via the ‘migrant-in-the-family’ model, still remains the preferred approach to providing long-term care in Italy. Though bedevilled with problems, domestic eldercare represents a strategic choice for Italian families as well as migrant workers. Based on the findings emerging from the study, we proffer four practical policy recommendations to improve the model in the future: better and easier financial assistance; increasing the role of the welfare state; introducing holistic help-desks; and reviewing policies on qualification and its valorization

Quantitative Assessment of Eye Phenotypes for Functional Genetic Studies Using Drosophila melanogaster

About two-thirds of the vital genes in the Drosophila genome are involved in eye development, making the fly eye an excellent genetic system to study cellular function and development, neurodevelopment/degeneration, and complex diseases such as cancer and diabetes. We developed a novel computational method, implemented as Flynotyper software (http://flynotyper.sourceforge.net), to quantitatively assess the morphological defects in the Drosophila eye resulting from genetic alterations affecting basic cellular and developmental processes. Flynotyper utilizes a series of image processing operations to automatically detect the fly eye and the individual ommatidium, and calculates a phenotypic score as a measure of the disorderliness of ommatidial arrangement in the fly eye. As a proof of principle, we tested our method by analyzing the defects due to eye-specific knockdown of Drosophila orthologs of 12 neurodevelopmental genes to accurately document differential sensitivities of these genes to dosage alteration. We also evaluated eye images from six independent studies assessing the effect of overexpression of repeats, candidates from peptide library screens, and modifiers of neurotoxicity and developmental processes on eye morphology, and show strong concordance with the original assessment. We further demonstrate the utility of this method by analyzing 16 modifiers of sine oculis obtained from two genome-wide deficiency screens of Drosophila and accurately quantifying the effect of its enhancers and suppressors during eye development. Our method will complement existing assays for eye phenotypes and increase the accuracy of studies that use fly eyes for functional evaluation of genes and genetic interactions

Human iPSC derived disease model of MERTK-associated retinitis pigmentosa

Retinitis pigmentosa (RP) represents a genetically heterogeneous group of retinal dystrophies affecting mainly the rod photoreceptors and in some instances also the retinal pigment epithelium (RPE) cells of the retina. Clinical symptoms and disease progression leading to moderate to severe loss of vision are well established and despite significant progress in the identification of causative genes, the disease pathology remains unclear. Lack of this understanding has so far hindered development of effective therapies. Here we report successful generation of human induced pluripotent stem cells (iPSC) from skin fibroblasts of a patient harboring a novel Ser331Cysfs*5 mutation in the MERTK gene. The patient was diagnosed with an early onset and severe form of autosomal recessive RP (arRP). Upon differentiation of these iPSC towards RPE, patient-specific RPE cells exhibited defective phagocytosis, a characteristic phenotype of MERTK deficiency observed in human patients and animal models. Thus we have created a faithful cellular model of arRP incorporating the human genetic background which will allow us to investigate in detail the disease mechanism, explore screening of a variety of therapeutic compounds/reagents and design either combined cell and gene- based therapies or independent approaches.This work was supported by Andalusian Health Council (PI-0324-2013), Instituto de Salud Carlos III (PI13/01331), Spanish Ministry of Economy and Competitiveness-FEDER BFU2012-36845, Instituto de Salud Carlos III RETICS RD12/0034/0010 and Academy of Finland (218050; 272808)

Association between Changes in Muscle Quality with Exercise Training and Changes in Cardiorespiratory Fitness Measures in Individuals with Type 2 Diabetes Mellitus: Results from the HART-D Study

Introduction: Type 2 diabetes mellitus (T2DM) is associated with a reduction in muscle quality. However, there is inadequate empirical evidence to determine whether changes in muscle quality following exercise are associated with improvement in cardiorespiratory fitness (CRF) in individuals with T2DM. The objective of this study was to investigate the association between change in muscle quality following a 9-month intervention of aerobic training (AT), resistance training (RT) or a combination of both (ATRT) and cardiorespiratory fitness (CRF) in individuals with T2DM. Material and Methods A total of 196 participants were randomly assigned to a control, AT, RT, or combined ATRT for a 9-months intervention. The exposure variable was change in muscle quality [(Post: leg muscle strength/leg muscle mass)-[(Pre: leg muscle strength/leg muscle mass)]. Dependent variables were change in CRF measures including absolute and relative VO2peak, and treadmill time to exhaustion (TTE) and estimated metabolic equivalent task (METs). Results Continuous change in muscle quality was independently associated with change in absolute (β = 0.015; p = 0.019) and relative (β = 0.200; p = 0.005) VO2peak, and TTE (β = 0.170; p = 0.043), but not with estimated METs (p > 0.05). A significant trend was observed across tertiles of change in muscle quality for changes in absolute (β = 0.050; p = 0.005) and relative (β = 0.624; p = 0.002) VO2peak following 9 months of exercise training. No such association was observed for change in TTE and estimated METs (p > 0.05). Discussion: The results from this ancillary study suggest that change in muscle quality following exercise training is associated with a greater improvement in CRF in individuals with T2DM. Given the effect RT has on increasing muscle quality, especially as part of a recommended training program (ATRT), individuals with T2DM should incorporate RT into their AT regimens to optimize CRF improvement

"I know that you know that I know": neural substrates associated with social cognition deficits in DM1 patients

Myotonic dystrophy type-1 (DM1) is a genetic multi-systemic disorder involving several organs including the brain. Despite the heterogeneity of this condition, some patients with non-congenital DM1 can present with minimal cognitive impairment on formal testing but with severe difficulties in daily-living activities including social interactions. One explanation for this paradoxical mismatch can be found in patients' dysfunctional social cognition, which can be assessed in the framework of the Theory of Mind (ToM). We hypothesize here that specific disease driven abnormalities in DM1 brains may result in ToM impairments. We recruited 20 DM1 patients who underwent the "Reading the Mind in the Eyes" and the ToM-story tests. These patients, together with 18 healthy controls, also underwent resting-state functional MRI. A composite Theory of Mind score was computed for all recruited patients and correlated with their brain functional connectivity. This analysis provided the patients' "Theory of Mind-network", which was compared, for its topological properties, with that of healthy controls. We found that DM1 patients showed deficits in both tests assessing ToM. These deficits were associated with specific patterns of abnormal connectivity between the left inferior temporal and fronto-cerebellar nodes in DM1 brains. The results confirm the previous suggestions of ToM dysfunctions in patients with DM1 and support the hypothesis that difficulties in social interactions and personal relationships are a direct consequence of brain abnormalities, and not a reaction symptom. This is relevant not only for a better pathophysiological comprehension of DM1, but also for non-pharmacological interventions to improve clinical aspects and impact on patients' success in life

Klf15 Is Critical for the Development and Differentiation of Drosophila Nephrocytes

Insect nephrocytes are highly endocytic scavenger cells that represent the only invertebrate model for the study of human kidney podocytes. Despite their importance, nephrocyte development is largely uncharacterised. This work tested whether the insect ortholog of mammalian Kidney Krüppel-Like Factor (Klf15), a transcription factor required for mammalian podocyte differentiation, was required for insect nephrocyte development. It was found that expression of Drosophila Klf15 (dKlf15, previously known as Bteb2) was restricted to the only two nephrocyte populations in Drosophila, the garland cells and pericardial nephrocytes. Loss of dKlf15 function led to attrition of both nephrocyte populations and sensitised larvae to the xenotoxin silver nitrate. Although pericardial nephrocytes in dKlf15 loss of function mutants were specified during embryogenesis, they failed to express the slit diaphragm gene sticks and stones and did not form slit diaphragms. Conditional silencing of dKlf15 in adults led to reduced surface expression of the endocytic receptor Amnionless and loss of in vivo scavenger function. Over-expression of dKlf15 increased nephrocyte numbers and rescued age-dependent decline in nephrocyte function. The data place dKlf15 upstream of sns and Amnionless in a nephrocyte-restricted differentiation pathway and suggest dKlf15 expression is both necessary and sufficient to sustain nephrocyte differentiation. These findings explain the physiological relevance of dKlf15 in Drosophila and imply that the role of KLF15 in human podocytes is evolutionarily conserve

The consequences of the glitch in the interactive virtual environment.

Esta investigación pretende averiguar qué papel tiene el glitch, ya sea fortuito o intencionado, en el entorno virtual interactivo. El interés por tratar este tema surge como respuesta ante la falta de estudios enfocados en estos efectos. De igual manera, también surge de la reacción de la comunidad de jugadores ante estos fallos y por el potencial estético que tienen algunas de las capturas de estos fallos. El propósito es descubrir las consecuencias de estos efectos glitch, tanto los modificados como los inesperados, en espacios virtuales asociados con el videojuego, a fin de valorar, en ambos casos, las variaciones que provocan, principalmente, en el apartado visual, pero también en el mecánico y en el narrativo. Para eso, se ha optado por un enfoque académico-teórico para la construcción de la base teórica, así como se ha hecho uso del método art-based research para que la práctica artística entre en diálogo con la teórica y, finalmente, se ha hecho uso del método de programación extrema para el desarrollo práctico. Esta investigación se divide en dos bloques principales: el teórico y el práctico. El bloque teórico tiene dos vertientes: la primera pasa por un análisis de las definiciones que se le ha ido dando al concepto glitch y glitch-art, entrando también en la investigación sobre las distintas técnicas de producción glitch. La segunda parte va enfocada en los videojuegos que exploran la aplicación del glitch y las obras artísticas que cuentan con el videojuego como medio. El bloque práctico y resultado de la investigación consiste en un entorno virtual creado con Blender y Unity. Se compone de seis escenas por las que se puede navegar y experimentar, de primera mano, los efectos de distorsión glitch que se han aplicado. Con todo esto, se ha podido concluir de manera resumida que, a tra- vés del proceso de construcción de espacios y aplicación de efectos glitch, encontramos distintos recursos que pueden ser útiles por su valor formal y cromático. Se pueden rescatar fragmentos de imagen que tienen interés, ya que proporcionan nuevas formas y representaciones debido a su carácter parcialmente aleatorio. También se puede concluir que no todos los glitches que se aplican a estas experiencias pueden dar como resultado imágenes o experiencias de calidad, y que no se puede pretender tampoco que en el glitch no controlado proporcione una experiencia enriquecedora. Aun así, este tema de investigación es lo suficientemente amplio como para poder seguir trabajando en él. Con un buen estudio sobre las posibilidades se pueden crear experiencias que exploten aún más estos efectos.This research aims to find out what role the glitch, whether accidental or intentional, plays in the interactive virtual environment. The interest in addressing this issue arises in response to the lack of studies focusing on these effects. Likewise, it also arises from the reaction of the gaming community to these glitches and from the aesthetic potential that some of the captures of these glitches have. The purpose is to discover the consequences of these glitch effects, both modified and unexpected, in virtual spaces associated with videogames, in order to assess, in both cases, the variations they cause, mainly in the visual section, but also in the mechanical and narrative ones. For this purpose, an academic-theoretical approach has been chosen for the construction of the theoretical base, as well as the use of the art-based research method for the artistic practice to come in dialogue with the theoretical one and, finally, the use of the extreme programming method for the practical development. This research is divided into two main blocks: the theoretical and the practical. The theoretical block has two aspects: the first one goes through an analysis of the definitions that have been given to the concept glitch and glitch-art, also getting into the research on the different glitch production techniques. The second part focuses on videogames that explore the application of glitch and artistic works that use videogames as a medium. The practical block and result of the research consist of a virtual environment created with Blender and Unity. It consists of six scenes through which you can navigate and experience, at first hand, the glitch distortion effects that have been applied. With all this, it has been possible to conclude in a summarized way that, through the process of construction of spaces and application of glitch effects, we find different resources that can be useful for their formal and chromatic value. Fragments of images can be rescued that are of interest, since they provide new forms and representations due to their partially random character. It can also be concluded that not all glitches applied to these experiences can result in quality images or experiences, and that it cannot be claimed either that the uncontrolled glitch provides an enriching experience. Even so, this research topic is sufficiently broad to be able to continue working on it. With a good study of the possibilities, experiences can be created that further exploit these effects.Depto. de Diseño e ImagenFac. de Bellas ArtesTRUEsubmitte