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Abstract Background Late‐onset Pompe disease (LOPD) is a genetic disorder characterized by progressive degeneration of the skeletal muscles produced by a deficiency of the enzyme acid alpha‐glucosidase. Enzymatic replacement therapy with recombinant human alpha‐glucosidase seems to reduce the progression of the disease; although at the moment, it is not completely clear to what extent. Quantitative muscle magnetic resonance imaging (qMRI) is a good biomarker for the follow‐up of fat replacement in neuromuscular disorders. The aim of this study was to describe the changes observed in fat replacement in skeletal muscles using qMRI in a cohort of LOPD patients followed prospectively. Methods A total of 36 LOPD patients were seen once every year for 4 years. qMRI, several muscle function tests, spirometry, activities of daily living scales, and quality‐of‐life scales were performed on each visit. Muscle MRI consisted of two‐point Dixon studies of the trunk and thigh muscles. Computer analysis of the images provided the percentage of muscle degenerated and replaced by fat in every muscle (known as fat fraction). Longitudinal analysis of the measures was performed using linear mixed models applying the Greenhouse–Geisser test. Results We detected a statistically significant and continuous increase in mean thigh fat fraction both in treated (+5.8% in 3 years) and in pre‐symptomatic patients (+2.6% in 3years) (Greenhouse–Geisser p < 0.05). As an average, fat fraction increased by 1.9% per year in treated patients, compared with 0.8% in pre‐symptomatic patients. Fat fraction significantly increased in every muscle of the thighs. We observed a significant correlation between changes observed in fat fraction in qMRI and changes observed in the results of the muscle function tests performed. Moreover, we identified that muscle performance and mean thigh fat fraction at baseline visit were independent parameters influencing fat fraction progression over 4 years (analysis of covariance, p < 0.05). Conclusions Our study identifies that skeletal muscle fat fraction continues to increase in patients with LOPD despite the treatment with enzymatic replacement therapy. These results suggest that the process of muscle degeneration is not stopped by the treatment and could impact muscle function over the years. Hereby, we show that fat fraction along with muscle function tests can be considered a good outcome measures for clinical trials in LOPD patients.

Quantitative MRI is an increasingly used method to monitor disease progression in muscular disorders due to its ability to measure changes in muscle fat content (reported as fat fraction) over a short period. Being able to objectively measure such changes is crucial for the development of new treatments in clinical trials. However, the analysis of the images involved continues to be a daunting task because of the time needed. Whether a more specific analysis selecting individual muscles or a global one analyzing the whole thigh or compartments could be a suitable alternative has only been marginally studied. In our study we compare three methods of analysis of 2-point-dixon images in a cohort of 34 patients with late onset Pompe disease followed over a period of one year. We measured fat fraction on MRIs obtained at baseline and at year 1, and we calculated the increment of fat fraction. We correlated the results obtained with the results of muscle function tests to investigate whether the three methods of analysis were equivalent or not. We observed significant differences between the three methods in the estimation of the fat fraction at both baseline and year 1, but no difference was found in the increment in fat fraction between baseline and year 1. When we correlated the fat fraction obtained with each method and the muscle function tests, we found a significant correlation with most tests in all three methods, although in most comparisons the highest correlation coefficient was found with the analysis of individual muscles. We conclude that the fastest strategy of analysis assessing compartments or the whole thigh could be reliable for certain cohorts of patients where the variable to study is the fat increment. In other sorts of studies, an individual muscle approach seems the most reliable technique.

Introduction: Duchenne (DMD) and Becker (BMD) muscular dystrophy are X-linked muscular disorders produced by mutations in the DMD gene which encodes the protein dystrophin. Both diseases are characterized by progressive involvement of skeletal, cardiac, and respiratory muscles. As new treatment strategies become available, reliable biomarkers and outcome measures that can monitor disease progression are needed for clinical trials.Methods: We collected clinical and functional data and blood samples from 19 DMD patients, 13 BMD patients, and 66 healthy controls (8 pediatric and 58 adult controls), and blood samples from 15 patients with dysferlinopathy (DYSF) and studied the serum concentration of 4 growth factors involved in the process of muscle fibrosis. We correlated the serum concentration of these growth factors with several muscle function tests, spirometry results and fat fraction identified by quantitative Dixon muscle MRI.Results: We found significant differences in the serum concentration of Platelet Derived Growth Factor-AA (PDGF-AA) between DMD patients and pediatric controls, in Connective Tissue Growth Factor (CTGF) between BMD patients and adult controls, and in and Transforming Growth Factor- β1 (TGF-β1) between BMD and DYSF patients. PDGF-AA showed a good correlation with several muscle function tests for both DMD and BMD patients and with thigh fat fraction in BMD patients. Moreover, PDGF-AA levels were increased in muscle biopsies of patients with DMD and BMD as was demonstrated by immunohistochemistry and Real-Time PCR studies.Conclusion: Our study suggests that PDGF-AA should be further investigated in a larger cohort of DMD and BMD patients because it might be a good biomarker candidate to monitor the progression of these diseases.

Objectives: Magnetization transfer (MT) imaging exploits the interaction between bulk water protons and protons contained in macromolecules to induce signal changes through a special radiofrequency pulse. MT detects muscle damage in patients with neuromuscular conditions, such as limb-girdle muscular dystrophies or Charcot-Marie-Tooth disease, which are characterized by progressive fiber loss and replacement by fatty tissue. In Pompe disease, in which there is, in addition, an accumulation of glycogen inside the muscle fibers, MT has not been tested yet. Our aim is to estimate MT ratio (MTR) in the skeletal muscle of these patients and correlate it with intramuscular fat fraction (FF) and results of muscle function tests.Methods: We obtained two-point axial Dixon and Dixon-MT sequences of the right thigh on a 1.5 Teslas MRI scanner in 60 individuals, including 29 late onset Pompe disease patients, 2 patients with McArdle disease, and 29 age and sex matched healthy controls. FF and MTR were estimated. Muscle function using several muscle function tests, including quantification of muscle strength, timed test quality of life scales, conventional spirometry obtaining forced vital capacity while sitting and in the supine position, were assessed in all patients.Results: MTR was significantly lower in Pompe patients compared with controls (45.5 ± 8.5 vs. 51.7 ± 2.3, Student T-test, p < 0.05). There was a negative correlation between the MTR and FF muscles studied (correlation coefficient: −0.65, Spearman test: p < 0.05). MTR correlated with most of the muscle function test results. We analyzed if there was any difference in MTR values between Pompe patients and healthy controls in those muscles that did not have an increase in fat, a measure that could be related to the presence of glycogen in skeletal muscles, but we did not identify significant differences except in the adductor magnus muscle (48.4 ± 3.6 in Pompe vs. 51 ± 1.3 in healthy controls, Student T-test = 0.023).Conclusions: MTR is a sensitive tool to identify muscle loss in patients with Pompe disease and shows a good correlation with muscle function tests. Therefore, the MT technique can be useful in monitoring muscle degeneration in Pompe disease in clinical trials or natural history studies.

Abstract Late onset Pompe disease (LOPD) is a slow, progressive disorder characterized by skeletal and respiratory muscle weakness. Enzyme replacement therapy (ERT) slows down the progression of muscle symptoms. Reliable biomarkers are needed to follow up ERT-treated and asymptomatic LOPD patients in clinical practice. In this study, 32 LOPD patients (22 symptomatic and 10 asymptomatic) underwent muscle MRI using 3-point Dixon and were evaluated at the time of the MRI with several motor function tests and patient-reported outcome measures, and again after one year. Muscle MRI showed a significant increase of 1.7% in the fat content of the thigh muscles in symptomatic LOPD patients. In contrast, there were no noteworthy differences between muscle function tests in the same period of time. We did not observe any significant changes either in muscle MRI or in muscle function tests in asymptomatic patients over the year. We conclude that 3-point Dixon muscle MRI is a useful tool for detecting changes in muscle structure in symptomatic LOPD patients and could become part of the current follow-up protocol in daily clinics.

Neuroblasts represent the predominant migrating cell type in the adult mouse brain. There are, however, increasing evidences of migration of other neural precursors. This work aims at identifying in vivo endogenous early neural precursors, different from neuroblasts, able to migrate in response to brain injuries. The monoclonal antibody Nilo1, which unequivocally identifies type B astrocytes and embryonic radial glia, was coupled to magnetic glyconanoparticles (mGNPs). Here we show that Nilo1–mGNPs in combination with magnetic resonance imaging in living mice allowed the in vivo identification of endogenous type B astrocytes at their niche, as well as their migration to the lesion site in response to glioblastoma, demyelination, cryolesion or mechanical injuries. In addition, Nilo1+ adult radial glia-like structures were identified at the lesion site a few hours after damage. For all damage models used, type B astrocyte migration was fast and orderly. Identification of Nilo1+ cells surrounding an induced glioblastoma was also possible after intraperitoneal injection of the antibody. This opens up the possibility of an early identification of the initial damage site(s) after brain insults, by the migration of type B astrocytes.

Las úlceras de la extremidad inferior presentan una elevada prevalencia que guarda una relación directa con la edad. El predominio de úlceras abiertas es del 0,1 a 0,3% y su incidencia de tres a cinco nuevos casos por 1.000 personas al año. Cuando estas se curan, ocurren recidivas del 33 al 42% de los casos, padeciendo una de cada tres úlceras una recidiva en un periodo de nueve meses y alrededor del 60% a los cinco años. Los ácidos grasos hiperoxigenados (AGHO) han demostrado ser eficaces en la prevención de las úlceras de la extremidad inferior gracias a su acción favorable sobre la piel, puesto que aumentan la microcirculación sanguínea, impulsan la renovación celular epidérmica y mejoran notablemente la hidratación cutánea. En el presente estudio, hemos querido evaluar una posible disminución de la incidencia de recidivas de lesiones vasculares con el uso continuado de los ácidos grasos hiperoxigenados (AGHO) en emulsión (Mepentol® Leche), en el mismo grupo de pacientes tratados con el producto en un estudio anterior, en el que se obtuvieron excelentes resultados que demostraron su efectividad en la prevención de la aparición de nuevas lesiones en la piel tratada con Mepentol® Leche, así como en la mejora de los diferentes síntomas que acompañan a este tipo de úlceras. Para ello, se ha realizado un seguimiento de dos años, desde 2006 a 2008, de estos mismos pacientes con úlceras de la extremidad inferior ya resueltas, con el fin de valorar la incidencia de recidivas en este grupo.Lower extremity ulcers have a high prevalence, which has a direct relationship with age, his prevalence is 0.1 to 0.3%, and its incidence is three to five new cases per thousand people per year. When these healed, relapses occur in 33 to 42% of cases, one in trhee suffer ulcer recurrence in a period of nine months, and about 60% at five years. Hyper-oxygenated fatty acids has proven to be effective in preventing lower extremity ulcers due to its favorable action on the skin, increasing blood microcirculation, promoting epidermal cell turnover and significantly improving skin hydration. In this study we wanted to evaluate a possible reduction in the incidence of recurrence of vascular lesions with continued use of hyper-oxygenated fatty acids (AGHO) emulsion, Mepentol® Leche, in the same group of patients treated with the product in a previous study, in which excellent results were obtained which showed its effectiveness in preventing appearance of new lesions in the skin treated with Mepentol® Leche, as well as the improvement of various symptoms that accompany this type of ulcers. To do this, it has been monitoring two years, from 2006 to 2008, these same patients with lower extremity ulcers healed in order to assess the incidence of recurrences in this group.

Las úlceras vasculares y las úlceras de pie diabético suponen un grave problema sanitario que afecta a un gran número de pacientes y constituyen, por ello, un gran reto de trabajo para los profesionales de la salud. Los ácidos grasos hiperoxgenados (AGHO) han demostrado tener eficacia gracias a su acción favorable sobre la piel, aumentando la microcirculación sanguínea, impulsando la renovación celular epidérmica y mejorando notablemente la hidratación cutánea. Hemos evaluado la eficacia del producto Mepentol® Leche, una emulsión a base de ácidos grasos hiperoxigenados, Aloe barbadensis y Mimosa tenuiflora, en el cuidado de la piel y el alivio de los síntomas, en pacientes de riesgo o con úlceras vasculares y úlceras de pie diabético. Se demuestra un antes y un después en el uso sistemático de Mepentol® Leche, evitando la sequedad cutánea, reduciendo el prurito, escozor, dolor y eczema, y devolviendo la piel a su coloración normal.Vascular ulcers and diabetic foot ulcers present a health serious problem which affects a large number of patients, creating a major challenge for health professionals. Hyperoxygenated fatty acid dressings have proven to be effective thanks to their favorable action on the skin, increasing the microcirculation of the blood, promoting the renovation of the epidermic cells, and notably increasing cutaneous hydration. We evaluate the effectiveness of Mepentol® Leche, an emulsion based on Hyper-oxygenated fatty acids, Aloe barbadensis and Mimosa tenuiflora, used to treat the skin and alleviate symptoms in patients at risk or with vascular ulcers and diabetic foot ulcers. This study showed a turning point in applying this product systematically, avoiding skin dryness and reducing itching, stinging, pain and eczema while returning normal color to the skin.

PURPOSE: Compressed sensing (CS) has been widely applied to prospective cardiac cine MRI. The aim of this work is to study the benefits obtained by including motion estimation in the CS framework for small-animal retrospective cardiac cine. METHODS: We propose a novel B-spline-based compressed sensing method (SPLICS) that includes motion estimation and generalizes previous spatiotemporal total variation (ST-TV) methods by taking into account motion between frames. In addition, we assess the effect of an optimum weighting between spatial and temporal sparsity to further improve results. Both methods were implemented using the efficient Split Bregman methodology and were evaluated on rat data comparing animals with myocardial infarction with controls for several acceleration factors. RESULTS: ST-TV with optimum selection of the weighting sparsity parameter led to results similar to those of SPLICS; ST-TV with large relative temporal sparsity led to temporal blurring effects. However, SPLICS always properly corrected temporal blurring, independently of the weighting parameter. At acceleration factors of 15, SPLICS did not distort temporal intensity information but led to some artefacts and slight over-smoothing. At an acceleration factor of 7, images were reconstructed without significant loss of quality. CONCLUSION: We have validated SPLICS for retrospective cardiac cine in small animal, achieving high acceleration factors. In addition, we have shown that motion modelling may not be essential for retrospective cine and that similar results can be obtained by using ST-TV provided that an optimum selection of the spatiotemporal sparsity weighting parameter is performed.

En este artículo presentamos reflexiones sobre una propuesta pedagógica orientada a promover la escolarización de chicos y chicas en situación de calle y sus líneas de acción: la vinculación escolar y los talleres escolares. La vinculación escolar supone elaboración de intervenciones que favorezcan el posicionamiento de chicos y chicas como sujetos de la educación en las escuelas. Los talleres escolares son espacios educativos desarrollados en instituciones destinadas a esta población. Allí se promueven experiencias centradas en la construcción y apropiación de conocimientos. En el trabajo destacamos el papel del contexto y las particularidades que presenta esta población para prácticas educativas destinadas a ella, y reflexionamos sobre el problema de la democratización educativa en escenarios signados por la desigualdad social y educativa.

En este artículo analizamos cómo las regulaciones sociales, implicadas en toda formulación e implementación de políticas públicas, y educativas en particular, apelan a la inclusión educativa con un sesgo que, muchas veces, parte desde una visión psicologista de la pobreza aun cuando se enumeren causas estructurales y "objetivas". En la investigación que realizamos sobre el Programa Todos a Estudiar se observa, por un lado, cómo se enfatizan los efectos de la exclusión vinculados a la producción de una "baja autoestima" en los adolescentes que abandonaron sus estudios y, por el otro, una praxis cuasi misional que se despliega en el uso de categorías como rescate y recuperación para dar cuenta de las intervenciones socioeducativas que desarrollan diferentes sujetos implicados en la implementación del Programa. Sostenemos como hipótesis que en el hacer y decir de estos sujetos se produce una paradoja contradictoria: sostener que la escuela es el mejor -y casi único- lugar para los jóvenes al tiempo que considerar que las instituciones educativas son productoras centrales de aquellos procesos que profundizan la exclusión social.Neste artigo analisamos como as regulações sociais, presentes em toda formulação e implementação de políticas públicas, e educacionais em particular, se referem à noção de inclusão educacional com um viés que, muitas vezes, parte de uma visão psicologizada da pobreza, até mesmo quando são enumeradas causas estruturais e objetivas. Na investigação realizada no Programa Todos a Estudiar observa-se, por um lado, como são enfatizados os efeitos da exclusão unidos à produção de uma "baixa auto-estima" nos adolescentes que abandonaram os estudos; e, por outro, uma prática quase missionária que se manifesta no uso de categorias como salvamento e recuperação para dar conta das intervenções socioeducativas desenvolvidas pelos diferentes sujeitos envolvidos na implementação do Programa. Sustentamos como hipótese que, no fazer e dizer destes sujeitos, emerge um paradoxo contraditório: sustentar que a escola é o melhor -e quase único- lugar para a juventude, ao mesmo tempo em que considera as instituições educacionais como produtoras centrais dos processos que aprofundam a exclusão social.In this paper we analyse how social regulations, implicated in public and educative polices, use the idea of educative inclusion from a psychologism point of view of poverty while are mentioned structural and "objective" causes. Our research and fieldwork on the "Programa Todos a Estudiar" shows, in one hand, how the exclusion effects related to the low self esteem grows/rise in teenagers that had abandoned their studies and in the other hand, a quasi-missionary praxis related to the use of categories such as rescue, recuperation , etc. to mention the socio-educative intervention that different persons involved in the implementation of the Programme does. We assure, as a hypothesis on this paper, that what this individuals persons "does" and "says" produce a contradictory paradox: it is assumed that the school is the best -and unique- place for those teenagers and, at the same time, those educative institutions are considered as the central producers of the processes that promote the social exclusion.

Del conjunto de dimensiones que atraviesa la existencia de los niños que viven en contextos de pobreza urbana y diversidad cultural, nos interesa centrarnos en algunas de las que se hacen presentes en las escuelas a las que asisten, ubicadas en el cordón sur de la ciudad de Buenos Aires. Las distintas representaciones y practicas respecto de esta niñez contribuyen a la producción de espacios institucionales de inclusión / exclusión y en la conformación de los itinerarios sociales, escolares y urbanos que efectivamente transitan estos niños. Dar cuenta de estos cruces complejos es el objeto de este trabajo, cuyo material empirico se apoya en un amplio conjunto de entrevistas realizadas a directores de escuelas primarias de la zona mencionada.