Multiple Birthdating Analyses in Adult Neurogenesis: A Line-Up of the Usual Suspects

Analyzing the variation in different subpopulations of newborn neurons is central to the study of adult hippocampal neurogenesis. The acclaimed working hypothesis that different subpopulations of newborn, differentiating neurons could be playing different roles arouses great interest. Therefore, the physiological and quantitative analysis of neuronal subpopulations at different ages is critical to studies of neurogenesis. Such approaches allow cells of different ages to be identified by labeling them according to their probable date of birth. Until very recently, only neurons born at one specific time point could be identified in each experimental animal. However the introduction of different immunohistochemically compatible markers now enables multiple subpopulations of newborn neurons to be analyzed in the same animal as in a line-up, revealing the relationships between these subpopulations in response to specific influences or conditions. This review summarizes the current research carried out using these techniques and outlines some of the key applications

Accidental catheter removal in critically ill patients: a prospective and observational study

INTRODUCTION: The importance of accidental catheter removal (ACR) lies in the complications caused by the removal itself and by catheter reinsertion. To the best of our knowledge, no studies have analyzed accidental removal of various types of catheters in the intensive care unit (ICU). The objective of the present study was to analyze the incidence of ACR for all types of catheters in the ICU. METHODS: This was a prospective and observational study, conducted in a 24-bed medical/surgical ICU in a university hospital. We included all consecutive patients admitted to the ICU over 18 months (1 May 2000 to 31 October 2001). The incidences of ACR for all types of catheters (both per 100 catheters and per 100 catheter-days) were determined. RESULTS: A total of 988 patients were included. There were no significant differences in ACR incidence between the four central venous access sites (peripheral, jugular, subclavian and femoral) or between the four arterial access sites (radial, femoral, pedal and humeral). However, the incidence of ACR was higher for arterial than for central venous catheters (1.12/100 catheter-days versus 2.02/100 catheter-days; P < 0.001). The incidences of ACR/100 nonvascular catheter-days were as follows: endotracheal tube 0.79; nasogastric tube 4.48; urinary catheter 0.32; thoracic drain 0.56; abdominal drain 0.67; and intraventricular brain drain 0.66. CONCLUSION: We found ACR incidences for central venous catheter, arterial catheter, endotracheal tube, nasogastric tube and urinary catheter that are similar to those reported in previous studies. We could not find studies that analyzed the ACR for thoracic, abdominal, intraventricular brain and cardiac surgical drains, but we believe that our rates are acceptable. To minimize ACR, it is necessary to monitor its incidence carefully and to implement preventive measures. In our view, according to establish quality standards, findings should be reported as ACR incidence per 100 catheters and per 100 catheter-days, for all types of catheters

Onset of microglial entry into developing quail retina coincides with increased expression of active caspase-3 and is mediated by extracellular ATP and UDP

Microglial cell precursors located in the area of the base of the pecten and the optic nerve head (BP/ONH) start to enter the retina of quail embryos at the 7 th day of incubation (E7), subsequently colonizing the entire retina by central-to-peripheral tangential migration, as previously shown by our group. The present study demonstrates a precise chronological coincidence of the onset of microglial cell entry into the retina with a striking increase in death of retinal cells, as revealed by their active caspase-3 expression and TUNEL staining, in regions dorsal to the BP/ONH area, suggesting that dying retinal cells would contribute to the microglial cell inflow into the retina. However, the molecular mechanisms involved in this inflow are currently unclear. Extracellular nucleotides, such as ATP and UDP, have previously been shown to favor migration of microglia towards brain injuries because they are released by apoptotic cells and stimulate both chemotaxis and chemokinesis in microglial cells via signaling through purinergic receptors. Hence, we tested here the hypothesis that ATP and UDP play a role in the entry and migration of microglial precursors into the developing retina. For this purpose, we used an experimental model system based on organotypic cultures of E6.5 quail embryo retina explants, which mimics the entry and migration of microglial precursors in the in situ developing retina. Inhibition of purinergic signaling by treating retina explants with either apyrase, a nucleotide-hydrolyzing enzyme, or suramin, a broad spectrum antagonist of purinergic receptors, significantly prevents the entry of microglial cells into the retina. In addition, treatment of retina explants with either exogenous ATP or UDP results in significantly increased numbers of microglial cells entering the retina. In light of these findings, we conclude that purinergic signaling by extracellular ATP and UDP is necessary for the entry and migration of microglial cells into the embryonic retina by inducing chemokinesis in these cells

Arterial catheter-related infection of 2,949 catheters

INTRODUCTION: Which particular arterial catheter site is associated with a higher risk of infection remains controversial. The Centers for Disease Control and Prevention guidelines of 1996 and the latest guidelines of 2002 make no recommendation about which site or sites minimize the risk of catheter-related infection. The objective of the present study was to analyze the incidence of catheter-related local infection (CRLI) and catheter-related bloodstream infection (CRBSI) of arterial catheters according to different access sites. METHODS: We performed a prospective observational study of all consecutive patients admitted to the 24 bed medical and surgical intensive care unit of a 650 bed university hospital during three years (1 May 2000 to 30 April 2003). RESULTS: A total of 2,018 patients was admitted to the intensive care unit during the study period. The number of arterial catheters, the number of days of arterial catheterization, the number of CRLIs and the number of CRBSIs were as follows: total, 2,949, 17,057, 20 and 10; radial, 2,088, 12,007, 9 and 3; brachial, 112, 649, 0 and 0; dorsalis pedis, 131, 754, 0 and 0; and femoral, 618, 3,647, 11 and 7. The CRLI incidence was significantly higher for femoral access (3.02/1,000 catheter-days) than for radial access (0.75/1,000 catheter-days) (odds ratio, 1.5; 95% confidence interval, 1.10–2.13; P = 0.01). The CRBSI incidence was significantly higher for femoral access (1.92/1,000 catheter-days) than for radial access (0.25/1,000 catheter-days) (odds ratio, 1.9; 95% confidence interval, 1.15–3.41; P = 0.009). CONCLUSION: Our results suggest that a femoral site increases the risk of arterial catheter-related infection

El marco jurídico de las CMSP. Reflexiones a propósito de la experiencia en Irak

En los últimos quince años, funciones tradicionalmente desempeñadas por el Estado han ido siendo traspasadas a compañías militares y de seguridad privadas. Ciertos Estados y otro tipo de actores están recurriendo cada vez más a estas compañías en contextos de conflicto armado o en situaciones de reconstrucción postbélica. En Irak el fenómeno ha alcanzado unas dimensiones sin precedentes desde el inicio del proceso de externalización. El empleo de compañías militares y de seguridad privadas suscita numerosas cuestiones en lo relativo a su responsabilidad y control. Se afirma en ocasiones que hay un vacío legal en lo concerniente a las actuaciones de estas compañías. Sin embargo, existen normas tanto a nivel internacional como nacional: Derecho Internacional Humanitario, legislación iraquí y legislación de Estados Unidos resultan aplicables a este sector. Sin embargo, como demuestra el análisis del caso de Irak, los conceptos y la normativa vigentes son insuficientes para tratar el fenómeno. Es necesario emprender un proceso de adaptación de las normas para hacer frente a las nuevas realidades

Majoritarian Contests with Asymmetric Battlefields: An Experiment

We investigate a version of the classic Colonel Blotto game in which individual battles may have different values. Two players allocate a fixed budget across battlefields and each battlefield is won by the player who allocates the most to that battlefield. The winner of the game is the player who wins the battlefields with highest total value. We focus on the case where there is one large and several small battlefields, such that a player wins if he wins the large and any one small battlefield, or all the small battlefields. We compute the mixed strategy equilibrium for these games and compare this with choices from a laboratory experiment. The equilibrium predicts that the large battlefield receives more than a proportional share of the resources of the players, and that most of the time resources should be spread over more battlefields than are needed to win the game. We find support for the main qualitative features of the equilibrium. In particular, strategies that spread resources widely are played frequently, and the large battlefield receives more than a proportional share in the treatment where the asymmetry between battlefields is stronger.We thank Subhasish Chowdhury, Judith Avrahami, seminar participants at New York University, Keele University, University of East Anglia, University of the Basque Country, and conference participants at the Voting Power in Practice Symposium at LSE 2011, M-BEES 2011, SING7 2011, Contest, Mechanisms and Experiments Conference at Exeter 2012, SAET 2012, GAMES 2012 and ESEM-EEA 2013. The equilibrium computations were carried out on the High Performance Computing Cluster supported by the Research and Specialist Computing Support service at the University of East Anglia

Prolonged oral cannabinoid administration prevents neuroinflammation, lowers β-amyloid levels and improves cognitive performance in Tg APP 2576 mice

This is an Open Access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Background]: Alzheimer's disease (AD) brain shows an ongoing inflammatory condition and non-steroidal anti-inflammatories diminish the risk of suffering the neurologic disease. Cannabinoids are neuroprotective and anti-inflammatory agents with therapeutic potential. [Methods]: We have studied the effects of prolonged oral administration of transgenic amyloid precursor protein (APP) mice with two pharmacologically different cannabinoids (WIN 55,212-2 and JWH-133, 0.2 mg/kg/day in the drinking water during 4 months) on inflammatory and cognitive parameters, and on 18F-fluoro-deoxyglucose (18FDG) uptake by positron emission tomography (PET). [Results]: Novel object recognition was significantly reduced in 11 month old Tg APP mice and 4 month administration of JWH was able to normalize this cognitive deficit, although WIN was ineffective. Wild type mice cognitive performance was unaltered by cannabinoid administration. Tg APP mice showed decreased 18FDG uptake in hippocampus and cortical regions, which was counteracted by oral JWH treatment. Hippocampal GFAP immunoreactivity and cortical protein expression was unaffected by genotype or treatment. In contrast, the density of Iba1 positive microglia was increased in Tg APP mice, and normalized following JWH chronic treatment. Both cannabinoids were effective at reducing the enhancement of COX-2 protein levels and TNF-α mRNA expression found in the AD model. Increased cortical β-amyloid (Aβ) levels were significantly reduced in the mouse model by both cannabinoids. Noteworthy both cannabinoids enhanced Aβ transport across choroid plexus cells in vitro. [Conclusions]: In summary we have shown that chronically administered cannabinoid showed marked beneficial effects concomitant with inflammation reduction and increased Aβ clearance.This work was supported by the Spanish Ministry of Science and Technology (SAF 2005-02845 to M.L.C). A.M.M-M. was recipient a fellowship from the Ministry of Education and Science.Peer Reviewe