Age-dependent impairment of spine morphology and synaptic plasticity in hippocampal CA1 neurons of a presenilin 1 transgenic mouse model of Alzheimer's disease.

Presenilin 1 (PS1) mutations are responsible for a majority of early onset familial Alzheimer's disease (FAD) cases, in part by increasing the production of Abeta peptides. However, emerging evidence suggests other possible effects of PS1 on synaptic dysfunction where PS1 might contribute to the pathology independent of Abeta. We chose to study the L286V mutation, an aggressive FAD mutation which has never been analyzed at the electrophysiological and morphological levels. In addition, we analyzed for the first time the long term effects of wild-type human PS1 overexpression. We investigated the consequences of the overexpression of either wild-type human PS1 (hPS1) or the L286V mutated PS1 variant (mutPS1) on synaptic functions by analyzing synaptic plasticity and associated spine density changes from 3 to 15 months of age. We found that mutPS1 induces a transient increase observed only in 4- to 5-month-old mutPS1 animals in NMDA receptor (NMDA-R)-mediated responses and LTP compared with hPS1 mice and nontransgenic littermates. The increase in synaptic functions is concomitant with an increase in spine density. With increasing age, however, we found that the overexpression of human wild-type PS1 progressively decreased NMDA-R-mediated synaptic transmission and LTP, without neurodegeneration. These results identify for the first time a transient increase in synaptic function associated with L286V mutated PS1 variant in an age-dependent manner. In addition, they support the view that the PS1 overexpression promotes synaptic dysfunction in an Abeta-independent manner and underline the crucial role of PS1 during both normal and pathological aging.

Autoavaluació de la seguretat integral en centres educatius: memòria justificativa

Cada vegada són més els autors que remarquen la necessitat de que les organitzacions (i, particularment, les empreses) avaluïn els riscos per a la seguretat i la salut i que adoptin mesures per a evitar o controlar els riscos, des de l’aparició de la Directiva 89/391CEE de la Unió Europea, relativa a l’aplicació de mesures per a promoure la millora de la seguretat i la salut dels treballadors en el seu lloc de treball. A Espanya, el tema de la seguretat i la prevenció de riscos laborals va guanyant importància en el terreny social i econòmic des de l’aparició de la Llei de Prevenció de Riscos Laborals l’any 1995, també en els centres educatius, on cada vegada es parla més de la salut laboral dels docents, del nivell de seguretat en els centres educatius i dels riscos als quals s’exposen diàriament els alumnes, professors i personal d’administració i serveis. El present informe sintetitza el procés seguit per a la confecció de l’instrument d’autoavaluació de la seguretat integral en centres educatius.

Treatment of atypical hemolytic uremic syndrome and thrombotic microangiopathies: a focus on eculizumab.

Uncontrolled complement activation is central to the occurrence of atypical hemolytic uremic syndrome (aHUS) and can result in thrombotic microangiopathies (TMAs).These terms encompass a group of heterogenic inherited or acquired diseases that recent research suggests may be triggered by the complement cascade. Pathogenetic triggers of complement activation include immunologic disorders, genetics, infections, systemic diseases, pregnancy, drug administration, metabolic diseases, transplantation, or triggers of mixed cause. Hallmarks of aHUS and other TMAs include increased vascular endothelium thromboresistance, leukocyte adhesion to damaged endothelium, complement consumption, coagulation abnormalities, and vascular shear stress, whereas common end points of these mechanisms include hemolytic anemia, thrombocytopenia with microvascular infarction, and predisposition for decreased kidney function and other organ involvement. The central role of the complement cascade as a disease trigger suggests a possible therapeutic target. Eculizumab, a first-in-class humanized monoclonal anti-C5 antibody that has been successful in the treatment of paroxysmal nocturnal hemoglobinuria, a disorder of complement-induced hemolytic anemia, received approval for the treatment of aHUS in the United States and Europe in late 2011. We review the treatment of aHUS and other TMAs, focusing on the role of eculizumab, including its pharmacology, mechanism of action, and approved dosing recommendations and health economic considerations. Finally, the potential for future indications for eculizumab use in other complement-driven diseases is discussed.

Bone microarchitecture assessed by TBS predicts osteoporotic fractures independent of bone density: The manitoba study.

The measurement of BMD by dual-energy X-ray absorptiometry (DXA) is the "gold standard" for diagnosing osteoporosis but does not directly reflect deterioration in bone microarchitecture. The trabecular bone score (TBS), a novel gray-level texture measurement that can be extracted from DXA images, correlates with 3D parameters of bone microarchitecture. Our aim was to evaluate the ability of lumbar spine TBS to predict future clinical osteoporotic fractures. A total of 29,407 women 50 years of age or older at the time of baseline hip and spine DXA were identified from a database containing all clinical results for the Province of Manitoba, Canada. Health service records were assessed for the incidence of nontraumatic osteoporotic fracture codes subsequent to BMD testing (mean follow-up 4.7 years). Lumbar spine TBS was derived for each spine DXA examination blinded to clinical parameters and outcomes. Osteoporotic fractures were identified in 1668 (5.7%) women, including 439 (1.5%) spine and 293 (1.0%) hip fractures. Significantly lower spine TBS and BMD were identified in women with major osteoporotic, spine, and hip fractures (all p < 0.0001). Spine TBS and BMD predicted fractures equally well, and the combination was superior to either measurement alone (p < 0.001). Spine TBS predicts osteoporotic fractures and provides information that is independent of spine and hip BMD. Combining the TBS trabecular texture index with BMD incrementally improves fracture prediction in postmenopausal women. © 2011 American Society for Bone and Mineral Research.

Aplicación para la administración de departamento de venta de un centro comercial (iPhone)

Proyecto orientado a ser una herramienta, para poder controlar y gestionar el stock de un departamento de venta de un centro comercial. Basado en dos aplicaciones. La primera, destinada a ser la herramienta mediante la cual el administrador del departamento, puede crear el entorno bajo la cual va a funcionar, controlar el stock y todas las operaciones que se realizan. La segunda, ejecutada en una plataforma móvil (iPhone), será una herramienta de gran utilidad para los vendedores, que les permitirá controlar el stock y realizar gestiones.

Dinámica de usos de suelo y paisaje en la cuenca de la Tordera (1987, 1992, 1997 y 2002)

Por medio de este estudio se pretende describir la evolución cronológica (1987, 1992, 1997 y 2002) que ha tenido el uso del suelo, en toda el área que comprende la Cuenca del rio Tordera, localizada en Catalunya, entre las provincias de Barcelona y Girona. Dentro de la cuenca se encuentra el rio Tordera, que tiene al norte como zona de inicio principal al Parque Natural Montseny, pero que también recibe aportes desde Arbúcies y Santa Coloma de Farners, y desemboca en el delta de la Tordera ubicado entre Blanes y Malgrat de Mar. El análisis se enfoca en toda el área de la Cuenca, tratando de describir la dinámica en los usos de suelo y paisajes, además de como ha sido esta durante los periodos estudiados, considerando un poco a las posibles consecuencias y causas de los cambios. Esto gracias a la información extraída de mapas de uso de suelo de los años 1987,1992, 1997 y 2002, aunado también a la consulta de bibliografía que aporte mejores bases a la información. La amplitud e influencia de este cuenca, hacen que sea una zona de gran importancia, no solo por los servicios ambientales que ofrece a los ecosistemas de la zona, sino también desde un punto social, ya que favorece diferentes actividades económicas, que van desde las primarias hasta el sector de servicios, sin dejar de lado al sector industrial y a la construcción. Las razones por las cuales resulta interesante un estudio de este tipo, derivan de la necesidad, de conocer las transformaciones que ha sufrido la cuenca, en sus usos de suelo, ya sea por causas naturales ó también debido a la presión sufrida por actividades antropicas, que la han llevado a una diversifican de usos y sistemas ecológicos y sociales, etc. Lo cual tiene impactos no solo desde un punto de vista paisajístico sino que altera, la dinámica ecológica que se ha mantenido desde épocas muy remotas, generando variaciones en la ecología del paisaje, que deseamos expresar en este estudio.

Glutamate Transport Decreases Mitochondrial pH and Modulates Oxidative Metabolism in Astrocytes.

During synaptic activity, the clearance of neuronally released glutamate leads to an intracellular sodium concentration increase in astrocytes that is associated with significant metabolic cost. The proximity of mitochondria at glutamate uptake sites in astrocytes raises the question of the ability of mitochondria to respond to these energy demands. We used dynamic fluorescence imaging to investigate the impact of glutamatergic transmission on mitochondria in intact astrocytes. Neuronal release of glutamate induced an intracellular acidification in astrocytes, via glutamate transporters, that spread over the mitochondrial matrix. The glutamate-induced mitochondrial matrix acidification exceeded cytosolic acidification and abrogated cytosol-to-mitochondrial matrix pH gradient. By decoupling glutamate uptake from cellular acidification, we found that glutamate induced a pH-mediated decrease in mitochondrial metabolism that surpasses the Ca(2+)-mediated stimulatory effects. These findings suggest a model in which excitatory neurotransmission dynamically regulates astrocyte energy metabolism by limiting the contribution of mitochondria to the metabolic response, thereby increasing the local oxygen availability and preventing excessive mitochondrial reactive oxygen species production.

Comrades or Culprits? Donor Engagement and Budget Transparency in Aid Dependent Countries

Budget transparency has come to be considered a key aspect of governance. Over the past decade, donors have invested increasing resources in strengthening processes through which budget transparency in developing countries can be enhanced. According to the 2008 Open Budget Index (OBI) Report, however, aid dependency and budget transparency appear to be inversely correlated. This article looks at the role of donor agencies in promoting or preventing budget transparency in aid dependent countries. It analyzes data for a sample of 16 aid-dependent countries included in the OBI, to test some preliminary hypotheses and select six countries for which more detailed findings are then presented. All of these countries have implemented reforms aimed at enhancing budget transparency, with substantial donor support. These, however, often had only limited success, partly because they were not well adapted to the local context, and partly because donors put limited emphasis on improving public access to budget information. Donor efforts were also often offset by other characteristics of donor interventions, namely their fragmentation, lack of transparency, and limited use of program aid modalities such as budget support and pooled sector funding.

Effects of Non-Susceptible Hosts on the Infection with Trypanosoma cruzi of the Vector Triatoma infestans: an Experimental Model

We tested experimentally the effects of the presence of non-susceptible hosts on the infection with Trypanosoma cruzi of the vector Triatoma infestans. The experiment consisted in two treatments: with chickens, including two chickens (non-susceptible hosts) and two infected guinea pigs (susceptible hosts), and without chickens, including only two infected guinea pigs. The hosts were held unrestrained in individual metal cages inside a closed tulle chamber. A total of 200 uninfected T. infestans third instar nymphs were liberated in each replica, collected on day 14, and examined for infection and blood meal sources on day 32-36. The additional presence of chickens relative to infected guinea pigs: (a) significantly modified the spatial distribution of bugs; (b) increased significantly the likelihoods of having a detectable blood meal on any host and molting to the next instar; (c) did not affect the bugs' probability of death by predation; and (d) decreased significantly the overall percentage of T. infestans infected with T. cruzi. The bugs collected from inside or close to the guinea pigs' cages showed a higher infection rate (71-88%) than those collected from the chickens' cages (22-32%). Mixed blood meals on chickens and guinea pigs were detected in 12-21% of bugs. Although the presence of chickens would decrease the overall percentage of infected bugs in short term experiments, the high rate of host change of T. infestans would make this difference fade out if longer exposure times had been provided.

Ireland on the move: Enhancing opportunities for physical activity in the built environment

The Institute of Public Health in Ireland recently hosted a seminar on physical activity. The seminar presentations were: Ms Teresa Lavin, IPH - Physical activity and the built environment in Ireland Prof James Sallis, Professor of Psychology at San Diego State University and Director of Active Living Research - Translating evidence from physical activity research into practice.

Heritability of renal function in hypertensive families of African descent in the Seychelles (Indian Ocean).

BACKGROUND: We estimated the heritability of three measures of glomerular filtration rate (GFR) in hypertensive families of African descent in the Seychelles (Indian Ocean). METHODS: Families with at least two hypertensive siblings and an average of two normotensive siblings were identified through a national hypertension register. Using the ASSOC program in SAGE (Statistical Analysis in Genetic Epidemiology), the age- and gender-adjusted narrow sense heritability of GFR was estimated by maximum likelihood assuming multivariate normality after power transformation. ASSOC can calculate the additive polygenic component of the variance of a trait from pedigree data in the presence of other familial correlations. The effects of body mass index (BMI), blood pressure, natriuresis, along with sodium to potassium ratio in urine and diabetes, were also tested as covariates. RESULTS: Inulin clearance, 24-hour creatinine clearance, and GFR based on the Cockcroft-Gault formula were available for 348 persons from 66 pedigrees. The age- and gender-adjusted correlations (+/- SE) were 0.51 (+/- 0.04) between inulin clearance and creatinine clearance, 0.53 (+/- 0.04) between inulin clearance and Cockcroft-Gault formula and 0.66 (+/- 0.03) between creatinine clearance and Cockcroft-Gault formula. The age- and gender-adjusted heritabilities (+/- SE) of GFR were 0.41 (+/- 0.10) for inulin clearance, 0.52 (+/- 0.13) for creatinine clearance, and 0.82 (+/- 0.09) for Cockcroft-Gault formula. Adjustment for BMI slightly lowered the correlations and heritabilities for all measurements whereas adjustment for blood pressure had virtually no effect. CONCLUSION: The significant heritability estimates of GFR in our sample of families of African descent confirm the familial aggregation of this trait and justify further analyses aimed at discovering genetic determinants of GFR.

Valoración del insomnio, somnolencia diurna y fatiga inducida por anestesia

Aquest estudi tracta dels efectes dels anestèsics sobre els ritmes circadians y més concretament per a produir insomni, somnolència diürna i fatiga. Aquests símptomes es valoren amb escales validades (respectivament: Escala de la son de Epworth, escala de somnolència de Epworth i la escala de fatiga de Krupp). Es va realitzar en 30 pacients intervinguts de herniorrafia inguinal, als set dies es realitzava una enquesta (amb les escales abans esmentades). Contràriament al que esperàvem es va trobar una disminució en les puntuacions dels tests al postoperatori.