Economic-environmental assessment of silvo-pastoral systems in Colombia: An ecosystem service perspective.

Cattle production in Colombia has an important social and economic role but causes considerable environmental impacts, such as deforestation and greenhouse gas emissions by ruminants, particularly methane. Thus, technological innovations aimed at reducing these impacts must focus on both economic and environmental sustainability. Silvo-pastoral systems (SPS) offer productivity increases while generating environmental benefits and ecosystem services and are therefore at the center of debate around sustainable production alternatives. The objective of this article is to evaluate the economic-environmental performance of two proposed SPS for a cattle fattening system for the Colombian context: (i) Urochloa brizantha cv. Toledo and (ii) Urochloa hybrid cv. Cayman, both in association with Leucaena leucocephala trees for browsing and shade provision. They are compared with the respective base scenarios of only using the grasses in monocultures. The study consists of a financial analysis, which estimates potential profitability increases in beef production in the SPS, and an environmental evaluation, which estimates the monetary values of microclimatic regulation and reduction of methane emissions. The value of methane emission reductions is then integrated into a combined economic-environmental evaluation. Results show that both SPS improve the profitability indicators of the production system and reduce the probability of economic loss. Likewise, the reduction of methane emissions in the SPS is estimated at US$6.12 per cattle, and the economic value of microclimatic regulation at US$2,026 per hectare.

Potential Forage Hybrid Markets for Enhancing Sustainability and Food Security in East Africa.

The cattle sector is strategic for both the economic development and food security of Africa, but the low availability and quality of forage puts the most vulnerable population at risk. Hybrid forages are an alternative for enhancing both food security and sustainability of the sector but adoption levels are still low in Africa, which is related to various factors such as the availability of seeds. This document analyzes potential markets for new interspecific hybrids of Urochloa and potential hybrids of Megathyrsus maximus, adapted to the environmental conditions of eastern and partially western Africa, applying a four-step methodology based on estimating (i) required forage amounts for each country according to its dairy herd, (ii) potential hectares for forage cultivation based on (i), (iii) hectares that can be covered by the two hybrids of interest according to a Target Population of Environment approach, and (iv) potential market values for each country and hybrid. The results show a potential market of 414,388 ha for new interspecific hybrids of Urochloa and 528,409 ha for potential hybrids of Megathyrsus maximus, with approximate annual values of 73.5 and 101.1 million dollars, respectively. Ethiopia, Tanzania, and Kenya hold a market share of 70% for Urochloa, and South Sudan, Ethiopia, and Tanzania a 67% market share for Megathyrsus maximus. The results will help different actors in decision-making, i.e., regarding private sector investments in forage seed commercialization or public sector incentives supporting adoption processes, and thus contribute to increasing food security and sustainability in the region.

Translational validity and implications of pharmacotherapies in preclinical models of Down syndrome.

Neurodevelopmental disorders are challenging to study in the laboratory, and despite a large investment, few novel treatments have been developed in the last decade. While animal models have been valuable in elucidating disease mechanisms and in providing insights into the function of specific genes, the predictive validity of preclinical models to test potential therapies has been questioned. In the last two decades, diverse new murine models of Down syndrome (DS) have been developed and numerous studies have demonstrated neurobiological alterations that could be responsible for the cognitive and behavioral phenotypes found in this syndrome. In many cases, similar alterations were found in murine models and in individuals with DS, although several phenotypes shown in animals have yet not been confirmed in the human condition. Some of the neurobiological alterations observed in mice have been proposed to account for their changes in cognition and behavior, and have received special attention because of being putative therapeutic targets. Those include increased oxidative stress, altered neurogenesis, overexpression of the Dyrk1A gene, GABA-mediated overinhibition and Alzheimer's disease-related neurodegeneration. Subsequently, different laboratories have tested the efficacy of pharmacotherapies targeting these alterations. Unfortunately, animal models are limited in their ability to mimic the extremely complex process of human neurodevelopment and neuropathology. Therefore, the safety and efficacy identified in animal studies are not always translated to humans, and most of the drugs tested have not demonstrated any positive effect or very limited efficacy in clinical trials. Despite their limitations, though, animal trials give us extremely valuable information for developing and testing drugs for human use that cannot be obtained from molecular or cellular experiments alone. This chapter reviews some of these therapeutic approaches and discusses some reasons that could account for the discrepancy between the findings in mouse models of DS and in humans, including: (i) the incomplete resemble of the genetic alterations of available mouse models of DS and human trisomy 21, (ii) the lack of evidence that some of the phenotypic alterations found in mice (e.g., GABA-mediated overinhibition, and alterations in adult neurogenesis) are also present in DS individuals, and (iii) the inaccuracy and/or inadequacy of the methods used in clinical trials to detect changes in the cognitive and behavioral functions of people with DS. Despite the shortcomings of animal models, animal experimentation remains an invaluable tool in developing drugs. Thus, we will also discuss how to increase predictive validity of mouse models.

El estudiante de medicina ante el síndrome de Down. Cuidados a las personas / No disponible

El cuidado a las personas con síndrome de Down parte de un principio fundamental: La esencia se asienta en que es un ser humano; lo accesorio es que tiene síndrome de Down. El cuidado a la persona exige contemplarla como tal: con sus necesidades y sus capacidades. Función indispensable de los médicos es el atender a la problemática médica mediante la aplicación de específicos programas de salud. El bienestar físico le ayudará a alcanzar el mayor bienestar psico-social. El taller analizará este programa, expondrá las modernas tareas educativas y psico-sociales, y dará oportunidad para que personas adultas con síndrome de Down muestren su realidad y experiencias

The care to individuals with Down syndrome should be based upon an essential principle: the person is a human being. Having Down syndrome is just an accidental element. Coping the care requires addressing the entire person, including both limitations and the abilities. The main function of the medical profession is to care for the physical health through the use of good health programs. The physical quality of life will help to secure the best psychosocial well-being. This workshop will offer and summarize, first, the health program; second, it will explain the current educational and psychosocial practices; third, it will give the opportunity to a lady with Down syndrome to show the highlights and experiences of her life

Del conocimiento al servicio: conocer más para servir mejor / No disponible

Nuestro cerebro recibe la información que, gracias a la reflexión, se convierte y almacena en él en forma de conocimiento. De la mano del conocimiento el individuo opta por una determinada acción, decide. Esa opción viene condicionada por múltiples influencias, propias y externas. Es preciso incorporar e integrar la idea de servicio dentro de nuestros circuitos cerebrales, como argumento permanente en nuestra toma de decisiones. El mundo de la discapacidad ofrece un terreno especial para promover y cultivar la idea de servicio, llamada a manifestar los atributos trascendentales del ser humano: la verdad, la bondad y la belleza

Informative inputs reach the brain where, through reflection, are integrated and stored as knowledge. Knowledge leads to action that is individually selected, and consistently influenced by internal and external experiences. It becomes essential to include and integrate the concept and the reality of service into the cerebral circuits, in a way that it may permanently participate into the realm of decision-taking processes. The world of disability offers excellent opportunities to promote and develop the idea of service. It will help to make visible and to enlighten the transcendent attributes of human beings, namely the truth, the goodness and the beauty

Los hermanos: la nueva era / No disponible

El autor, basándose en un reciente estudio de Cuskelly, reflexiona sobre las nuevas orientaciones que deben ser ofrecidas a los hermanos con síndrome de Down, ante las realidades de una nueva era. La vida de estas personas se ha prolongado notablemente, con todas sus consecuencias de diversos signos; las familias son más reducidas; los padres, de edad también más avanzada, muestran mayores limitaciones

The author relies on a recent research performed by Cuskelly on the intention to care of siblings of individuals with Down syndrome. The lives of these individuals have been prolonged and expanded in possibilities, offering consequences of different sign; the number of subjects in a family has been reduced; and the aged parents may not be capable to cope with these new challenges. New orientations should be offered to the siblings along these lines

Fundamentos de una terapéutica racional en el síndrome de Down / No disponible

El esperanzador futuro que se nos abre actualmente con la moderna farmacología de los estimulantes cognitivos en el síndrome de Down, cimentada en la experimentación con sus modelos animales, no nos debe ocultar la inmensa capacidad terapéutica aplicada en los últimos cuarenta años. Ella ha sido la responsable de los espectaculares avances conseguidos en el campo de la salud, la educación, la psicología, la conducta y, en conjunto, de la calidad de vida. Una mirada serena y objetiva nos permitirá asociar los mejores métodos, tanto educativos como farmacológicos, en beneficio de cada persona concreta

Advances in genetic and molecular techniques and the development of experimental models in animals have facilitated the development of new approaches and strategies for the treatment of some symptoms of Down syndrome. However, no less spectacular have been the advances attained in the educative and behavioral dimensions of the individuals with Down syndrome during the last forty years. The modern neuroscience provides insights to better apply a combination of both biological and psychological tools, to enhance cognition and behavior of the people with Down syndrome

Neurodiversidad, discapacidad e inteligencias múltiples / No disponible

El autor rechaza la idea de sustituir el término de discapacidad por el de diversidad funcional, o el de discapacidad intelectual por el de neurodiversidad. Diversidad funcional y neurodiversidad son propiedades que definen a todo ser humano. Discapacidad intelectual, en cambio, queda definida por las limitaciones en las funciones cognitivas y conductas adaptativas que condicionan el funcionamiento en la vida diaria. En el desarrollo del cerebro humano se aprecian dos líneas fundamentales: la que es común a todos los individuos y define su condición humana, y la que es particular a cada uno y define sus cualidades personales e inteligencias múltiples. La neurociencia nos permite detectar y analizar los fallos en el desarrollo de estas dos líneas, que son el origen de la discapacidad intelectual, para poder elaborar los apoyos necesarios

The author holds that functional diversity cannot replace the concept of intellectual disability. Functional diversity is a condition that embraces all people. But intellectual disability is strictly defined by some dysfunction in both, cognitive functioning and adaptive behavior. In a similar vein, neurodiversity is a human quality embracing all individuals. Human brain is developed along two main lines: a common pathway that defines human condition, and an individual pathway which will account for personal qualities and multiple intelligences. Different and distinctive failures in the development and functioning of these two pathways in the brain will qualify and define each individual intellectual disability and its consequences. They are uncovered by the neuroscience, which will offer adequate solutions and support to the individual

El síndrome de Down en perspectiva 2016 / No disponible

Los progresos realizados en la atención, cuidados e investigación sobre el síndrome de Down han permitido avanzar considerablemente en la realidad vital de las personas. La visión optimista y esperanzadora que razonablemente nos captura, no debe ocultar los problemas que aún se plantean: la persistente visión negativa y excluyente que la sociedad continúa manteniendo; las diferencias en salud, habilidades, conducta, atención entre un individuo y otro; la problemática que plantea la irrupción de fármacos que pretenden mejorar las funciones cognitivas

Significant advances have been made in the research, care and attention to individuals with Down syndrome. The optimistic outlook should not overlook some persistent difficulties: the negative and rejecting vision of society; the inter-individual variability in medical, cognitive and behavioral concerns; and the challenges imposed by the use of incoming drugs positively tested in preclinical research

The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant.

The Koolen-de Vries syndrome (KdVS; OMIM #610443), also known as the 17q21.31 microdeletion syndrome, is a clinically heterogeneous disorder characterised by (neonatal) hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism. Expressive language development is particularly impaired compared with receptive language or motor skills. Other frequently reported features include social and friendly behaviour, epilepsy, musculoskeletal anomalies, congenital heart defects, urogenital malformations, and ectodermal anomalies. The syndrome is caused by a truncating variant in the KAT8 regulatory NSL complex unit 1 (KANSL1) gene or by a 17q21.31 microdeletion encompassing KANSL1. Herein we describe a novel cohort of 45 individuals with KdVS of whom 33 have a 17q21.31 microdeletion and 12 a single-nucleotide variant (SNV) in KANSL1 (19 males, 26 females; age range 7 months to 50 years). We provide guidance about the potential pitfalls in the laboratory testing and emphasise the challenges of KANSL1 variant calling and DNA copy number analysis in the complex 17q21.31 region. Moreover, we present detailed phenotypic information, including neuropsychological features, that contribute to the broad phenotypic spectrum of the syndrome. Comparison of the phenotype of both the microdeletion and SNV patients does not show differences of clinical importance, stressing that haploinsufficiency of KANSL1 is sufficient to cause the full KdVS phenotype.

Uso de rituximab en pacientes pediátricos con síndrome nefrótico córtico-resistente. Experiencia de un centro / Use of rituximab in pediatric patients with steroidresistant nephrotic syndrome. A single center study / Uso de rituximab em pacientes pediátricos com síndrome nefrótica córtico-resistente. Experiência de um centro

Introducción: los esteroides son el tratamiento de elección del síndrome nefrótico con tasas de éxito hasta del 90%. En pacientes que no responden adecuadamente a ellos, se han usado diferentes esquemas de inmunosupresión. Objetivo y métodos: describir la respuesta terapéutica en un grupo de siete niños con síndrome nefrótico córtico-dependiente (SNCD) o córtico-resistente (SNCR) que recibieron tratamiento con rituximab y micofenolato mofetil en un hospital universitario de la ciudad de Medellín durante los años 2010-2012. Resultados: dos pacientes tenían SNCD y cinco, SNCR; la mediana de edad en el momento del diagnóstico fue de 2 años (p25-75: 1-5); seis meses después de la aplicación del rituximab se encontró disminución de la proteinuria en el 93% de los pacientes; los esteroides se lograron suspender en el 100%; además, disminuyó el número de recaídas; sin embargo, la proteinuria reapareció un año después de dicho tratamiento. Conclusión: con el rituximab disminuyen la proteinuria y la dosis de esteroides, pero la enfermedad recurre 12 meses después de usarlo. Se sugiere hacer otro estudio evaluando el efecto de una segunda dosis de rituximab al año de la primera.

Introduction: Steroids are the cornerstone of therapy for nephrotic syndrome (NS) with a remission rate as high as 90%. In patients who do not respond to them or are steroid dependent, other immunosuppressive drugs have been used. Although rituximab use in NS is off-label, many authors have published their experience with it. Objective and methods: To describe retrospectively a group of seven children with nephrotic syndrome, either steroid-dependent (SDNS) or steroid- resistant (SRNS), treated with rituximab and mycophenolate, at Pablo Tobón Uribe Hospital, in Medellín, Colombia. Results: Two patients with SDNS and five with SRNS were evaluated; median age at diagnosis was 2 years (p25-75: 1-5); six months after treatment with rituximab there was reduction in proteinuria (93%), in the steroid dose (100%) and in the relapse episodes. However, proteinuria reappeared 12 months after treatment. Conclusion: During the first year after rituximab treatment of NS there is reduction in proteinuria and in the steroid dose, but thereafter there is relapse. It is suggested to carry out another study using a second dose of rituximab one year after the first one.

Introdução: os esteroides são o tratamento de eleição da síndrome nefrótica com taxas de sucesso até da 90%. Em pacientes que não respondem adequadamente a eles, usaram-se diferentes esquemas de imunossupressão. Não está aprovado o uso do rituximab em pacientes com síndrome nefrótica, mas alguns grupos publicaram sua experiência com ele nesta doença. Objetivo e métodos: descrever a resposta terapêutica num grupo de sete meninos com síndrome nefrótica córtico-dependente (SNCD) ou córtico -resistente (SNCR) que receberam tratamento com rituximab e micofenolato mofetil num hospital universitário da cidade de Medellín durante os anos 2010-2012. Resultados: dois pacientes tinham SNCD e cinco, SNCR; a idade no momento do diagnóstico foi de 2 anos (p25-75: 1-5); seis meses depois da aplicação do rituximab se encontrou diminuição de 93% da proteinúria e de 100% na dose de prednisolona; ademais, diminuiu o número de recaídas; no entanto, a proteinúria reapareceu um ano depois de dito tratamento. Conclusão: com o rituximab diminuem a proteinúria e a dose de esteroides, mas a doença recorre 12 meses depois de usá-lo. Sugere-se fazer outro estudo avaliando o efeito de uma segunda dose de rituximab no ano seguinte da primeira dose.

Discapacidad intelectual y Neurociencia / No disponible

Ante el peligro de que la neurociencia sea vista y cuestionada como nueva herramienta al servicio del poder para marginar más sutilmente a la discapacidad intelectual, el autor analiza una reciente publicación de Altermark que parece acusar a la neurociencia de deslizarse en esa dirección. El artículo expone los fines, métodos y logros de la moderna neurociencia en el ámbito de la discapacidad intelectual, y defiende su extraordinaria aportación a la sociedad en general y a las personas con dicha condición en particular

In Altermark's view, modern neuroscience research may be underpinned by a discursive division between normal and pathological, thus enhancing the biopolitical power in the field of developmental disabilities. The author disclaims this opinion. He explains the aims, methods and achievements of neuroscience, which are contributing to a new age in the attention and care of individuals with mental disability

Overexpression of Dyrk1A is implicated in several cognitive, electrophysiological and neuromorphological alterations found in a mouse model of Down syndrome.

Down syndrome (DS) phenotypes result from the overexpression of several dosage-sensitive genes. The DYRK1A (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A) gene, which has been implicated in the behavioral and neuronal alterations that are characteristic of DS, plays a role in neuronal progenitor proliferation, neuronal differentiation and long-term potentiation (LTP) mechanisms that contribute to the cognitive deficits found in DS. The purpose of this study was to evaluate the effect of Dyrk1A overexpression on the behavioral and cognitive alterations in the Ts65Dn (TS) mouse model, which is the most commonly utilized mouse model of DS, as well as on several neuromorphological and electrophysiological properties proposed to underlie these deficits. In this study, we analyzed the phenotypic differences in the progeny obtained from crosses of TS females and heterozygous Dyrk1A (+/-) male mice. Our results revealed that normalization of the Dyrk1A copy number in TS mice improved working and reference memory based on the Morris water maze and contextual conditioning based on the fear conditioning test and rescued hippocampal LTP. Concomitant with these functional improvements, normalization of the Dyrk1A expression level in TS mice restored the proliferation and differentiation of hippocampal cells in the adult dentate gyrus (DG) and the density of GABAergic and glutamatergic synapse markers in the molecular layer of the hippocampus. However, normalization of the Dyrk1A gene dosage did not affect other structural (e.g., the density of mature hippocampal granule cells, the DG volume and the subgranular zone area) or behavioral (i.e., hyperactivity/attention) alterations found in the TS mouse. These results suggest that Dyrk1A overexpression is involved in some of the cognitive, electrophysiological and neuromorphological alterations, but not in the structural alterations found in DS, and suggest that pharmacological strategies targeting this gene may improve the treatment of DS-associated learning disabilities.

Organización de redes neuronales en el cerebro del síndrome de Down / No disponible

Todas las funciones cerebrales -sensoriales, motoras, cognitivas, conductuales- son el resultado de la actividad de las neuronas. Pero éstas no funcionan de manera aislada sino que conforman intrincadas redes y circuitos perfectamente establecidos, gracias a los cuales se van originando los elementos que sustancian la percepción, la conciencia, el conocimiento, etc. Cuanto más compleja sea la función a desarrollar, más complicada y extensa será la red neuronal responsable de poner en marcha y mantener dicha función. El número de unidades neuronales y de sus conexiones está reducido en ciertas zonas del cerebro del síndrome de Down, por lo que las redes y circuitos que conforman tendrán una menor extensión y una menor capacidad organizativa, lo que constituye la base del decremento en la expresión de determinadas habilidades. Pero ¿es posible que en el síndrome de Down la reducción de la actividad de una zona cerebral afectada pueda ser sustituida o compensada por la actividad de otra, menos o nada afectada?

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Chronic melatonin treatment rescues electrophysiological and neuromorphological deficits in a mouse model of Down syndrome.

The Ts65Dn mouse (TS), the most commonly used model of Down syndrome (DS), exhibits several key phenotypic characteristics of this condition. In particular, these animals present hypocellularity in different areas of their CNS due to impaired neurogenesis and have alterations in synaptic plasticity that compromise their cognitive performance. In addition, increases in oxidative stress during adulthood contribute to the age-related progression of cognitive and neuronal deterioration. We have previously demonstrated that chronic melatonin treatment improves learning and memory and reduces cholinergic neurodegeneration in TS mice. However, the molecular and physiological mechanisms that mediate these beneficial cognitive effects are not yet fully understood. In this study, we analyzed the effects of chronic melatonin treatment on different mechanisms that have been proposed to underlie the cognitive impairments observed in TS mice: reduced neurogenesis, altered synaptic plasticity, enhanced synaptic inhibition and oxidative damage. Chronic melatonin treatment rescued both impaired adult neurogenesis and the decreased density of hippocampal granule cells in trisomic mice. In addition, melatonin administration reduced synaptic inhibition in TS mice by increasing the density and/or activity of glutamatergic synapses in the hippocampus. These effects were accompanied by a full recovery of hippocampal LTP in trisomic animals. Finally, melatonin treatment decreased the levels of lipid peroxidation in the hippocampus of TS mice. These results indicate that the cognitive-enhancing effects of melatonin in adult TS mice could be mediated by the normalization of their electrophysiological and neuromorphological abnormalities and suggest that melatonin represents an effective treatment in retarding the progression of DS neuropathology.

Infecciones respiratorias en niños con síndrome de Down / No disponible

Los problemas respiratorios son causa importante de morbilidad y mortalidad en los niños con síndrome de Down. Recientemente han aparecido en la literatura mundial cinco artículos que abordan aspectos distintos de las infecciones respiratorias en niños con síndrome de Down. Ofrecemos un resumen de estos artículos, con aportación especial sobre la respuesta inmunitaria, y haremos especial énfasis en la infección por el virus respiratorio sincitial, por ser el más problemático y el que plantea la necesidad de tomar una línea de acción que esté justificada y sea bien ponderada. La peculiaridad del quinto artículo es que ofrece el estado de la cuestión desde la perspectiva de la Unión Europea (AU)

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Rehabilitación cognitiva de las personas con síndrome de Down: Perspectivas disciplinares de normalización / No disponible

Los autores reivindican la necesidad de una intervención específica, rehabilitadora y multidisciplinar de las personas con síndrome de Down, que vaya fundamentada en los recientes avances consegudios en las áreas de la neuropsicología, la educación, la genética, la bioquímica, la farmacología y la logopedia), que vaya orientada a la normalización parcial de las personas con síndrome de Down, y tenga en cuenta la totalidad del desarrollo, pero sin descartar el criterio de precocidad de forma absoluta. Animan a las asociaciones que defienden y apoyan a las personas con síndrome de Down a que exijan a las instituciones públicas la financiación necesaria para que: 1) se formen profesionales en estas técnicas de rehabilitación, y 2) se garantice el acceso a todas las personas que lo necesitan a estos nuevos programas de normalización. Es algo de interés general, incluso visto desde una perspectiva puramente económica, ya que cuanto más evolucionada y capaz sea una persona con síndrome de Down desde múltiples puntos de vista, más autónoma será y, por tanto, menos costosa para la sociedad. Asimismo las asociaciones deberían orientar y guiar a los padres en su particular aproximación a las nuevas perspectivas terapéuticas (AU)

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Evolución a largo plazo de los niños con diagnóstico de síndrome nefrótico atendidos en el Hospital Universitario San Vicente de Paúl, Medellín, entre enero de 1960 y diciembre de 2009 / Long-term follow-up of pediatric patients with nephrotic syndrome treated at Hospital Universitario San Vicente de Paúl (Medellín (HUSVP), Colombia), between January 1960 and December 2009

Introducción: el síndrome nefrótico (SN) es una de las enfermedades glomerulares más frecuentes en la infancia y son pocos los estudios realizados en Colombia sobre esta enfermedad. Objetivo: describir las características clínicas y epidemiológicas de los niños con SN atendidos en el Hospital Universitario San Vicente de Paúl, de Medellín, Colombia, entre los años 1960-2009. Metodología: estudio descriptivo retrospectivo. Resultados: el 87,9% de los pacientes fueron corticosensibles, entre 1,7%-5,4% se tornaron corticorresistentes. La histopatología predominante fue la del síndrome nefrótico con cambios mínimos (43,6%) seguida por la glomeruloesclerosis focal y segmentaria (37,3%). El 40% requirieron inmunosupresión adicional; en 88,8% de estos se utilizó ciclofosfamida con remisión en 85,7%. Se presentaron complicaciones en 56% y 52% de ellas fueron infecciosas. El 9% de los pacientes llegaron a la insuficiencia renal crónica. La tasa de mortalidad fue del 5,7%. Discusión: esta es una de las series más grandes de pacientes con SN reportadas hasta el momento y con un período de seguimiento de hasta 35 años, lo que aporta información valiosa sobre el comportamiento local de la enfermedad y la respuesta al tratamiento inmunosupresor, El seguimiento a largo plazo de estos pacientes es fundamental para ofrecer el mejor tratamiento disponible y nos plantea nuevos interrogantes sobre la evolución del SN en nuestra población.

Introduction: Nephrotic syndrome (NS) is a glomerular disease that frequently affects children. There have been few studies on it in Colombia. Objective: To describe the clinical and epidemiological features of children with SN treated at HUSVP between 1960 and 2009. Methodology: Retrospective and descriptive study. Results: Steroid-sensitive nephrotic syndrome was diagnosed in 87.9% of the patients, and between 1.7%-5.4% turned steroid-resistant. Biopsies revealed disease with minimal changes in 43.6% and focal segmental glomerulosclerosis in 37.3%. Additional immunosuppressive therapy was required by 40% of the patients; in 88.8% of these, cyclophosphamide was used, and remission was achieved in 85.7%. In 56% of the cases there were complications that were infectious in 52%. Nine percent of the patients progressed to end-stage renal disease. Mortality rate was 5.7%. Discussion: The large number of patients with nephrotic syndrome studied in this series and the long period of follow-up (up to 35 years) provide valuable information about the clinical behavior of this syndrome in Colombia and on its response to immunosuppressive therapy.

Reducing GABAA α5 receptor-mediated inhibition rescues functional and neuromorphological deficits in a mouse model of down syndrome.

Down syndrome (DS) is associated with neurological complications, including cognitive deficits that lead to impairment in intellectual functioning. Increased GABA-mediated inhibition has been proposed as a mechanism underlying deficient cognition in the Ts65Dn (TS) mouse model of DS. We show that chronic treatment of these mice with RO4938581 (3-bromo-10-(difluoromethyl)-9H-benzo[f]imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]diazepine), a selective GABA(A) α5 negative allosteric modulator (NAM), rescued their deficits in spatial learning and memory, hippocampal synaptic plasticity, and adult neurogenesis. We also show that RO4938581 normalized the high density of GABAergic synapse markers in the molecular layer of the hippocampus of TS mice. In addition, RO4938581 treatment suppressed the hyperactivity observed in TS mice without inducing anxiety or altering their motor abilities. These data demonstrate that reducing GABAergic inhibition with RO4938581 can reverse functional and neuromorphological deficits of TS mice by facilitating brain plasticity and support the potential therapeutic use of selective GABA(A) α5 NAMs to treat cognitive dysfunction in DS.

Long-term oral administration of melatonin improves spatial learning and memory and protects against cholinergic degeneration in middle-aged Ts65Dn mice, a model of Down syndrome.

Ts65Dn mice (TS), the most commonly used model of Down syndrome (DS), exhibit phenotypic characteristics of this condition. Both TS mice and DS individuals present cognitive disturbances, age-related cholinergic degeneration, and increased brain expression of ß-amyloid precursor protein (AßPP). These neurodegenerative processes may contribute to the progressive cognitive decline observed in DS. Melatonin is a pineal indoleamine that has been reported to reduce neurodegenerative processes and improve cognitive deficits in various animal models. In this study, we evaluated the potentially beneficial effects of long-term melatonin treatment on the cognitive deficits, cholinergic degeneration, and enhanced AßPP and ß-amyloid levels of TS mice. Melatonin was administered for 5 months to 5- to 6-month-old TS and control (CO) mice. Melatonin treatment improved spatial learning and memory and increased the number of choline acetyltransferase (ChAT)-positive cells in the medial septum of both TS and CO mice. However, melatonin treatment did not significantly reduce AßPP or ß-amyloid levels in the cortex or the hippocampus of TS mice. Melatonin administration did reduce anxiety in TS mice without inducing sensorimotor alterations, indicating that prolonged treatment with this indoleamine is devoid of noncognitive behavioral side effects (e.g., motor coordination, sensorimotor abilities, or spontaneous activity). Our results suggest that melatonin administration might improve the cognitive abilities of both TS and CO mice, at least partially, by reducing the age-related degeneration of basal forebrain cholinergic neurons. Thus, chronic melatonin supplementation may be an effective treatment for delaying the age-related progression of cognitive deterioration found in DS.