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The activity and the metabolism of the brain change rhythmically during the day/night cycle. Such rhythmicity is also observed in cultured neurons from the suprachiasmatic nucleus, which is a critical center in rhythm maintenance. However, this issue has not been extensively studied in cultures from areas less involved in timekeeping, as the hippocampus. Using neurons cultured from the hippocampi of newborn rats (both male and female), we observed significant time-dependent changes in global activity, in synaptic vesicle dynamics, in synapse size, and in synaptic mRNA amounts. A transcriptome analysis of the neurons, performed at different times over 24 h, revealed significant changes only for RNA-binding motif 3 (Rbm3). RBM3 amounts changed, especially in synapses. RBM3 knockdown altered synaptic vesicle dynamics and changed the neuronal activity patterns. This procedure also altered local translation in synapses, albeit it left the global cellular translation unaffected. We conclude that hippocampal cultured neurons can exhibit strong changes in their activity levels over 24 h, in an RBM3-dependent fashion.SIGNIFICANCE STATEMENTThis work is important in several ways. First, the discovery of relatively regular activity patterns in hippocampal cultures implies that future studies using this common model will need to take the time parameter into account, to avoid misinterpretation. Second, our work links these changes in activity strongly to RBM3, in a fashion that is independent of the canonical clock mechanisms, which is a very surprising observation. Third, we describe here probably the first molecule (RBM3) whose manipulation affects translation specifically in synapses, and not at the whole-cell level. This is a key finding for the rapidly growing field of local synaptic translation.

La presente investigación tiene como objetivo principal analizar la gestión del Programa Vaso de Leche en el distrito de Santiago de Surco, con miras a determinar su eficacia, los alcances obtenidos; así como proponer mejoras para renovar el Programa y sensibilizar a sus actores. El Vaso de Leche es un programa nacional asistencial dirigido a mejorar la calidad de vida de la población con más alto riesgo nutricional, grupos empobrecidos asentados en las áreas rurales y urbano-marginales. Este Programa está a cargo de los gobiernos locales, en relación a su organización, administración de recursos y ejecución. El desarrollo de la investigación busca respuestas a varias interrogantes en relación al análisis de la gestión del servicio para obtener alcances sobre la percepción de la calidad del producto y el servicio recibido por los beneficiarios; la identificación de los actores clave y de cumplimiento de sus roles; la verificación de los mecanismos empleados para la selección de los beneficiarios; así como el análisis de los factores que facilitan o limitan la gestión administrativa, operativa y financiera del programa. Siguiendo estos objetivos, la forma de investigación aplicada es el estudio de caso, que logra esclarecer la gestión del Programa a través de sus principales actores del gobierno central, local y sociedad civil. Estos resultados permitirán obtener propuestas que contribuyan a fortalecer el Programa de la gestión municipal. Esta tesis se ha desarrollado de acuerdo a las pautas de la estrategia metodológica mixta, es decir, de tipo cualitativa y cuantitativa. En el extremo cualitativo, la principal fuente de información primaria son las entrevistas en profundidad a los principales actores y los conocimientos adquiridos por observación directa en los diferentes momentos del proceso de investigación. De otro lado, se aplicó la estrategia cuantitativa, mediante la realización de encuestas para determinar el perfil del beneficiario surcano, entre otros aspectos. Los principales hallazgos son los siguientes: a) un porcentaje representativo de beneficiarios se encuentra dentro de la línea de pobreza, b) existe escasa capacitación a las madres preparadoras respecto a la calidad de servicio y pasividad del beneficiario frente al Programa, c) la Municipalidad se muestra como el eje articulador del Programa, d) el registro y depuración de beneficiarios es irregular y está politizado. Además, se detectó la escasez de recursos humanos y presupuestales, la ausencia de un flujograma, la escasa vocación de servicio de los trabajadores; así como el incumplimiento de las actividades programadas. Todo ello permite concluir que el Programa se distancia de un desarrollo de gestión eficaz. Finalmente, la presente tesis sugiere el fortalecimiento de las capacidades en los diferentes roles desde una perspectiva de Gerencia Social, proponiendo estrategias que permitan alcanzar un desarrollo eficaz y sostenible del Programa. The main objective of the present research is to analyze the management of the Vaso de Leche Program in Santiago de Surco district, with the purpose to determine its effectiveness and the results obtained; as well as proposing improvements to renovate it with a sensitization of its actors. The Vaso de Leche was created as a priority poverty - alleviation program to improve the life quality of some population with a high malnutrition risk, a poor sector that settled in rural areas and others who were marginalized on the outskirts of the urban center. The local governments through Peru are in charge of this program, in relation to its organization, resource management and execution. This research looks for responses to several questions about this program, regarding the analysis the service management about the perceptions of the product quality that is gave to the beneficiaries, the description and duties of every actor that is involved in this program. Likewise, examine the mechanisms that are used by the local government in the beneficiaries’ selection process and the analysis of the factors about the institutional – operational management, including its strength and weakness. In this context, the research method applied is the Case Study that helped to understand the program management involving the main actors such as the central and local government including the women organization. These results allow obtaining recommendations that would contribute to enforce the Program of the local management. This thesis has been developed by the guidelines of the mixed methodological strategy, which means both qualitative and quantitative. On the qualitative extreme, the main source of information was the in-depth interviews with the main actors and the knowledge acquired by direct observation at the different moments of the research process. On the other hand, the quantitative strategy was applied, by conducting 361 surveys during the beneficiaries’ census to determine the district beneficiary profile, among other aspects. The main findings infer that a representative percentage of beneficiaries is within the poverty line, there is partial training on women regarding quality of service, the Santiago de Surco Municipality is shown as the main articulation actor of the Program, registration and elimination of the beneficiaries is irregular and politicized. In addition, the shortage of human and budgetary resources, the absence of a flow chart, the non-relevant vocation, as well as the nonfulfilled of the programmed activities, allow this research to conclude that the Vaso de Leche program distances itself from an effective management. Finally, this thesis recommends the strengthening of the capacities in the different actor’s roles from a social management perspective, proposing strategies that allow reaching an effective and sustainable development of this Program. Tesis

Mesenchymal stem/stromal cells (MSCs) have been investigated for the treatment of diseases that affect the cardiovascular system, including Chagas disease. MSCs are able to promote their beneficial actions through the secretion of proregenerative and immunomodulatory factors, including insulin-like growth factor-1 (IGF-1), which has proregenerative actions in the heart and skeletal muscle. Here, we evaluated the therapeutic potential of IGF-1-overexpressing MSCs (MSC_IGF-1) in a mouse model of chronic Chagas disease. C57BL/6 mice were infected with Colombian strain Trypanosoma cruzi and treated with MSCs, MSC_IGF-1, or vehicle (saline) six months after infection. RT-qPCR analysis confirmed the presence of transplanted cells in both the heart and skeletal muscle tissues. Transplantation of either MSCs or MSC_IGF-1 reduced the number of inflammatory cells in the heart when compared to saline controls. Moreover, treatment with MSCs or MSC_IGF-1 significantly reduced TNF-α, but only MSC treatment reduced IFN-γ production compared to the saline group. Skeletal muscle sections of both MSC- and MSC_IGF-1-treated mice showed a reduction in fibrosis compared to saline controls. Importantly, the myofiber area was reduced in T. cruzi-infected mice, and this was recovered after treatment with MSC_IGF-1. Gene expression analysis in the skeletal muscle showed a higher expression of pro- and anti-inflammatory molecules in MSC_IGF-1-treated mice compared to MSCs alone, which significantly reduced the expression of TNF-α and IL-1β. In conclusion, our results indicate the therapeutic potential of MSC_IGF-1, with combined immunomodulatory and proregenerative actions to the cardiac and skeletal muscles.

ObjectiveTo describe and compare characteristics of older adults who drive after drinking and those who do not, whether an intervention addressing at-risk drinking reduces risk among those reporting driving after drinking, and reasons reported for driving after drinking.MethodsSecondary data analysis of a randomized trial testing the efficacy of a multifaceted intervention to reduce at-risk drinking among adults with a mean age of 68 years in primary care (N = 631).ResultsAlmost a quarter of at-risk drinkers reported driving after drinking (N = 154). Compared to those who did not drive after drinking, those who did were more likely to be younger, male, and working. They consumed a higher average number of drinks per week, had more reasons they were considered at-risk drinkers, and were more likely to meet at-risk drinking criteria due to amount of drinking and binge drinking. Those driving after drinking at baseline reduced the frequency of this behavior at 3 and 12 months and there were no statistically significant differences in the proportions of persons still engaging in driving after drinking among those who were assigned to intervention or control groups. Reasons for driving after drinking included not thinking that it was a problem and having to get home.ConclusionsDriving after drinking is common in this population of older, at-risk drinkers recruited in primary care settings and, like younger adults, men and those reporting binge drinking are more likely to engage in this behavior. Given that this behavior is dangerous and the population of older adults is fast growing, interventions addressing driving after drinking are needed.

Autism is a developmental disorder characterized by social deficits, impaired communication, and restricted and repetitive patterns of behaviour. Emerging theories indicate interregional functional and anatomical brain connectivity as a likely key feature in autism pathophysiology. Corpus callosum (CC) represents a natural target of autism connectivity research, being the expression of interhemispheric communication. In this paper, a novel method for a robust morphometric analysis of CC data is presented. The standard morphometric approach is based on the analysis of the size and shape of the CC midsagittal cross-section. As there are no gross anatomical landmarks that clearly delimit anatomically or functionally distinct CC regions, several geometric partitioning schemes have been proposed in the literature for morphometric analysis, subdividing CC into subregions whose fiber topography is expected to target different hemispheric cortical regions. A novel tool of morphometric analysis, based on the automated subdivision of a high number of partitions from a CC centroid and on the consequent determination of the CC anatomical landmarks is presented, allowing an automated analysis of CC volumes, shapes and curvatures, suitable for an automated application in clinical environment. Moreover the proposed tool can be used for original post-processing and visualization techniques that may help in the analysis of possible alterations of CC and in the correlations with autism-related diseases. The proposed morphometric tool has been validated and applied for clinical investigation on brain morphometry in children (age 3-11 years) with autism or with other autism spectrum disorders (DSA) and on healthy control subjects who underwent volumetric MRI T1 weighted acquisitions.

The present reflection refers to the survival of elements of the primary ritual within the contemporary media and communication. The media setting is the new contemporary social concentration and from that point on, we understand that culture contents, such as ritual practices, also become present within the media. On the other hand, the media sphere itself becomes a possibility and reality because of the recurrent use of these ritual elements. Thus, we can identify the retrofeeding between the cultural and media imaginary worlds, confirming the close relation among ritual, social bond of the group and social communication. A presente reflexão trata da sobrevivência de elementos do ritual primitivo na Comunicação e na Mídia contemporâneas. Se por um lado, o espaço midiático é o novo locus social contemporâneo, e dai compreende-se que conteúdos da cultura tais como as práticas rituais também se tornem presentes no espaço da mídia, por outro lado, a própria esfera midiática se viabiliza e legitima a partir do uso recorrente desses elementos do ritual. Neste sentido, podemos identificar o processo de retroalimentação entre os imaginários cultural e midiático, reafirmando a estreita relação entre ritual, vinculação social do grupo e comunicação social. Tentamos compreender a busca de um reencantamento, ainda que simulado, operado pela sociedade contemporânea pós-industrial por meio das práticas midiáticas.

Non parasitic splenic cysts are an uncommon clinical and pathologic entities, out of these, epitelias splenic cysts (ESC) occurred in 10% of cases. Until recently the treatment of choice for the large ESC consisted of splenectomy. Splenic preservation, for avoiding risks of sepsis, is a modern concept uniformly accepted for treating childhood splenic injury and benign pathology. The Authors report a case of prenatal diagnosis of large left upper quadrant mass that was apparent at Ultrasonography (US) at 32th week of gestational age. Laparotomy at 3rd day of life: a large cyst splenic mass was found (7 x 7 cm), it was situated all in lower pole. Partial splenectomy was performed; cysts were not found in other organs. Histology of specimen: ESC. The postoperative course was uneventful. Postoperative (6 months) Scintigraphy demonstrated the good vascularization of the spleen.