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Pauci-immune necrotizing crescentic glomerulonephritis is the histologic substrate of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Several studies in animal models have demonstrated the crucial role of complement activation in the pathogenesis of ANCA-associated vasculitis, but only small series have analyzed the prognostic implications of complement glomerular deposits. This study aimed to assess the clinical and prognostic implications of C3d- and C4d-positive glomerular staining in renal vasculitis. Eighty-five patients with a diagnosis of pauci-immune necrotizing crescentic glomerulonephritis were included in the study. C3d and C4d were analyzed by immunohistochemical staining using a polyclonal antibody. The primary predictors were glomerular C3d- and C4d-positive staining. The primary end point was the cumulative percentage of patients who developed end-stage renal disease. Glomerular staining for C3d and C4d was observed in 42 (49.4%) of 85 biopsies and 38 (44.7%) of 85 biopsies, respectively. C3d-positive staining was associated with the severity of renal impairment and with a lower response rate to treatment (P=.003 and P=.04, respectively). Renal survival at 2 and 5 years was 60.9% and 51.8% in C3d-positive patients compared with 87.7% and 78.9% in C3d-negative patients (P=.04). C4d-positive staining did not show any impact in renal outcome. When adjusted by renal function and other histologic parameters, C3d staining remained as an independent predictor for renal survival (hazard ratio, 2.5; 95% confidence interval, 1.1-5.7; P=.03). Therefore, this study demonstrates that C3d-positive glomerular staining is an independent risk factor for the development of end-stage renal disease in ANCA-associated renal vasculitis.

C3G, a Guanine nucleotide Exchange Factor (GEF) for Rap1 and R-Ras, has been shown to play important roles in development and cancer. Previous studies determined that C3G regulates cell death through down-regulation of p38α MAPK activity. Here, we found that C3G knock-down in MEFs and HCT116 cells promotes migration and invasion through Rap1-mediated p38α hyper-activation. These effects of C3G were inhibited by Rap1 knock-down or inactivation. The enhanced migration observed in C3G depleted HCT116 cells was associated with reduction in E-cadherin expression, internalization of ZO-1, actin cytoskeleton reorganization and decreased adhesion. We also found that matrix metalloproteases MMP2 and MMP9 are involved in the pro-invasive effect of C3G down-regulation. Additionally, our studies revealed that both C3G and p38α collaborate to promote growth of HCT116 cells in vitro and in vivo, possibly by enhancing cell survival. In fact, knocking-down C3G or p38α individually or together promoted cell death in vitro, although only the double C3G-p38α silencing was able to increase cell death within tumors. Notably, we found that the pro-tumorigenic function of C3G does not depend on p38α or Rap1 activation. Altogether, our studies uncover novel mechanisms by which C3G controls key aspects of tumorigenesis., This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (SAF2010-20918-C02-01 and SAF2013-48210-C2-02 to AP, SAF2010-20918-C02-02 and SAF2013-48210-C2-01 to CG), from Complutense University (AE1/14-18987 and UCM 920384 to AP), from the Council of Education from Junta de Castilla y León (SA157A12-1 to CG), and from the Cellex Foundation (PB). All funding was co-sponsored by the European FEDER Program. MA and NP are PhD student supported by the Spanish Ministry of Education (FPU fellowship). CS is a PhD student supported by SAF2013-48210-C2-02 grant. VM-G is supported by Dr. Moraza Foundation PhD fellowship. PB is supported by a Beatrius de Pinos postdoctoral Fellowship from the Generalitat de Catalunya (2014 BP-B 00160).

Microbial mats have been hypothesized to improve the persistence and the preservation of organic remains during fossilization processes. We test this hypothesis with long-term experiments (up to 5.5 years) using invertebrate and vertebrate corpses.Once placed on mats,the microbial community coats the corpses and forms a three-dimensional sarcophagus composed of microbial cells and exopolymeric substances (EPS). This coverage provides a template for i) moulding superficial features, resulting in negative impressions, and ii) generating replicas.The impressions of fly setulae, fish scales and frog skin verrucae are shaped mainly by small cells in an EPS matrix. Microbes also replicate delicate structures such as the three successive layers that compose a fish eye.The sarcophagus protects the body integrity, allowing the persistence of inner organs such as the ovaries and digestive apparatus in flies,the swim bladder and muscles in fish, and the bone marrow in frog legs.This study brings strong experimental evidence to the idea that mats favour metazoan fossilization by moulding, replicating and delaying decay. Rapid burial has classically been invoked as a mechanism to explain exceptional preservation. However, mats may play a similar role during early fossilization as they can preserve complex features for a long time, This work, which is part of the research projects CGL2013-42643P and the research grant supporting M. Iniesto were funded by the Spanish Ministry of Economy and Competitiveness. The SEM facility at IMPMC was supported by Region Ile de France grant SESAME 2006 I-07-593/R, INSU-CNRS, INP-CNRS, and University Pierre et Marie Curie, Paris. SEM analyses performed for this study were supported by a grant from the Foundation Simone et Cino Del Duca (PI: K. Benzerara). Some SEM observations were also conducted at SIdI UAM (Madrid). Environmental SEM observations were performed at the MNCN (Madrid)

This paper reports the results of experiments from an implementation of H-P2PSIP, a hierarchical overlay architecture based on the ongoing work in the IETF P2PSIP Working Group. This architecture allows the exchange of information among different independent overlay networks through the use of a two-layer architecture based on super-peers and hierarchical identifiers. The validation of this proposal is based on a Linux based real implementation where we have used four different scenarios with 1,000 peers in order to perform different experiments. We have obtained results for different parameters such as routing performance (number of hops), delay, routing state (number of overlay routing entries) and bandwidth consumption. This research was supported in part by the European Commission Seventh Framework Programme under grant agreement n 25774 (TREND Network of Excellence), Comunidad de Madrid grant S-2009/TIC-1468 (MEDIANET project) and Spanish MICINN grant TEC2011-29688-C02-02 (eeCONTENT project). Publicado

A seasonal study of extracellular enzyme activities (EEA) was conducted in the coastal, sandy aquifer system located in the greater fluvial-littoral ecosystem of Doñana (SW, Spain). Glucosidase, leucine aminopeptidase, alkaline phosphatase, and phenol oxidase activities were determined over a 2-year period in 30 piezometers spread in an area of approximately 100 km(2). Taking into account all enzymes, piezometers, and seasons, EEA ranged over several orders of magnitude, from 1.01 × 10(-5) ± 2.92 × 10(-6) to 1.37 ± 0.13 nmol (methylumbelliferyl, amido-4-methylcoumarin, or dihydroxyphenylalanine) mL(-1) h(-1). The quality, much more than the quantity, of organic matter and nutrients seemed to be the major variables that controlled the spatiotemporal patterns showed by EEA. EEA patterns obtained in this study agree with several functional models of microbial communities, such as optimal resource allocation and nutrient co-limitation. This study probably represents the first one in which these functional models have been tested in subsurface systems. Results obtained in this study seem to suggest that microbial communities inhabiting groundwaters in Doñana are not dead or compromised cells. By contrast, these communities play relevant roles in carbon and nutrient cycling, continue with the decomposition process that begins in the sediments of the shallow lakes located in the area, provide remineralized carbon and nutrients to producers of these surface aquatic systems, and close energy and matter cycles. This study proposes that groundwater systems should be considered dynamic systems, comparable in functional complexity to surface systems.

An immunocompetent 82-year-old female was admitted to our hospital due to fever without clear origin and hyponatremia. In the following days, an acute and bilateral pulmonary infiltrate appeared with a progressive worsening in respiratory function. Chest x-ray and CT (Computed tomography) showed bilateral reticulonodular infiltrates. Bronchoscopic aspiration and bronchoalveolar lavage (BAL), and transbronchial lung biopsy (TBBX) studies did not reveal microbiological and histopathological diagnosis. Broad-spectrum antibiotics were non-effective, and the patient died due to respiratory failure. Necropsy study revealed a miliary tuberculosis affecting lungs, liver, bone marrow, spleen, kidney, arteries, pancreas, and adrenal glands. Some weeks after the patient´s death, mycobacterial cultures from sputum, BAL and TBBX samples were positive for Mycobacterium tuberculosis. Sin financiación 3.405 JCR (2018) Q2, 45/133 Microbiology 1.310 SJR (2018) Q1, 69/298 Infectious Diseases No data IDR 2018 UEM

In the current Internet picture more than 70% of the hosts are located behind Network Address Translators (NATs). This is not a problem for the client/server paradigm. However, the Internet has evolved, and nowadays the largest portion of the traffic is due to peer-to-peer (p2p) applications. This scenario presents an important challenge: two hosts behind NATs (NATed hosts) cannot establish direct communications. The easiest way to solve this problem is by using a third entity, called Relay, that forwards the traffic between the NATed hosts. Although many efforts have been devoted to avoid the use of Relays, they are still needed in many situations. Hence, the selection of a suitable Relay becomes critical to many p2p applications. In this paper, we propose the Gradual Proximity Algorithm (GPA): a simple algorithm that guarantees the selection of a topologically close-by Relay. We present a measurement-based analysis, showing that the GPA minimizes both the delay of the relayed communication and the transit traffic generated by the Relay, being a QoS-aware and ISP-friendly solution. Furthermore, the paper presents the Peer-to-Peer NAT Traversal Architecture (P2P-NTA), which is a global, distributed and collaborative solution, based on the GPA. This architecture addresses the Relay discovery/selection problem. We have performed large-scale simulations based on real measurements, which validate our proposal. The results demonstrate that the P2P-NTA performs similarly to direct communications with reasonably large deployments of p2p applications. In fact, only 5% of the communications experience an extra delay that may degrade the QoS due to the use of Relays. Furthermore, the amount of extra transit traffic generated is only 6%. We also show that the P2P-NTA largely outperforms other proposals, where the QoS degradation affects up to more than 50% of the communications, and the extra traffic generated goes beyond 80%. This work has been partially funded by the Grants MEDIANET (S2009/TIC-1466) from the Regional Government of Madrid and CON-PARTE (TEC2007-67966-C03- 03) by the Ministry of Science and Innovation of Spain. Publicado

We conducted a seasonal research of the activities of microbial communities in a coastal, sandy aquifer system located in the Donana Natural Protected Area (SW, Spain). Groundwaters from 30 piezometers were sampled over a two-year period. The proportion of active microbial biomass ranged from 0.02 to 6.36% of the total microbial biomass, while the active microbial biomass ranged from 7.42 10 −3 2.20 10 −4 to 17.30 3.71 ngC mL −1 . Bacterial carbon production, measured through the incorporation of [ 3 H]leucine into cellular proteins, showed a mean value of 0.18 0.72 ngC mL −1 h −1 in all wells and all seasons. Bacterial growth rates ranged from 0.03 to 87.26 days. These activities exhibited spatiotemporal patterns. Temperature and the presence of nutrients and organic matter appear to be important factors controlling these patterns. However, hydrogeological flows, both local and regional, seemed to constitute the most important factor determining these spatiotemporal patterns, probably because the distrib...

Currently, aquifers are considered to be ecosystems that interchange materials and energy with other systems located in their surroundings. The aquifer system of Donana (southwest Spain) has been studied over recent decades from a hydrogeological point of view, although nothing is known about its biological or ecological aspects. In order to describe the general characteristics of its microbial communities, bacterial abundance, cell biomass, bacterial biomass and microbial activities of functional groups were investigated by sampling, over a 2-year period, 13 wells located in the vicinity of four very productive shallow lakes in the most superficial part of this coastal, sandy aquifer system. Multivariate analysis of variance (MANOVA) indicated differences in abundance and biomass variables among sampling locations, seasons and sampling locations × seasons. Principal component analysis showed that temperature and dissolved oxygen appeared to be the most important factors controlling the temporal variability of microbial communities. Hydrological connectivity between surface water and groundwater was important in the control of the spatiotemporal distribution of microbial communities. Due to this hydrological connection, the aquifer system and the wetlands constitute a unique entity, a unique ecosystem, called the “hydroecosystem”, where microbial communities could play a central ecological role.

The histopathologic classification of antineutrophil cytoplasmic antibody-associated vasculitis has been demonstrated to have prognostic value in small cohorts of patients with pauci-immune extracapillary glomerulonephritis. We aimed to validate this histologic subgrouping system in a large cohort of patients with renal vasculitis from 3 Spanish centers. The additional value of several histologic parameters for predicting renal outcome was investigated. A total of 151 biopsies of patients with renal vasculitis were reviewed and classified as follows: 41% crescentic, 24% mixed, 21% focal, and 14% sclerotic. The cumulative proportions of renal survival at 5 years were 83.2%, 81.2%, 60.5%, and 50.7% for the focal, mixed, crescentic, and sclerotic categories, respectively (P < .05). In the crescentic category, patients with less than 75% of glomeruli showing crescents had better survival at 1 and 5 years compared with those having greater than or equal to 75% of crescents (77.9% and 70.6% versus 51.3% and 45.6%; P = .02). When adjusted by renal function and other histologic parameters, the percentage of extracapillary proliferation and glomerulosclerosis remained as significant predictors for renal survival (hazard ratio, 1.03; 95% confidence interval, 1.01-1.05; P = .001, and hazard ratio, 1.03; 95% confidence interval, 1.01-1.05; P = .002, respectively). In conclusion, patients with pauci-immune crescentic glomerulonephritis experienced different outcomes depending on the percentage of crescents observed, so that extensive extracapillary proliferation was associated with the poorest renal survival. These findings validate the prognostic utility of the histologic classification scheme in antineutrophil cytoplasmic antibody positive and negative patients and suggest a subdivision of crescentic category (

Fungal molecular players involved in plant potassium nutrition via ectomycorrhizal associations. 2nd International Molecular Mycorrhiza Meeting IMMM 2015

Pauci-immune extracapillary glomerulonephritis (PEGN) is one of the most common causes of rapidly progressive glomerulonephritis and is usually associated with circulating anti-neutrophil cytoplasmic antibodies (ANCAs). However, a significant number of individuals with PEGN test negative for ANCA and this study aimed to analyze the characteristics of this subgroup of patients.Patients from two centres who were diagnosed with PEGN between 1997 and 2014 were studied retrospectively. Clinicopathological characteristics and renal outcome were compared between patients presenting with pauci-immune necrotizing extracapillary glomerulonephritis associated or not with the presence of circulating ANCA.Among the 114 patients with PEGN, 29 (25.4%) were ANCA negative. Compared with the 85 ANCA-positive patients, ANCA-negative patients were younger at the onset (54.8 ± 17.2 vs. 62 ± 14.0 years; P 0.05). The median level of urinary protein excretion was significantly higher among ANCA-negative patients (3.1 vs. 1 g/24 h; P 0.001), whereas no differences were found in renal function and need for dialysis between ANCA-negative and positive groups. Extrarenal involvement was present independently of ANCA status. Histological analysis showed that ANCA-negative patients were more likely to have mesangial proliferation (P 0.05). Renal and global survival were similar between ANCA-negative and positive patients, and treatment response and relapse rates were comparable in both groups.ANCA-negative pauci-immune extracapillary glomerulonephritis is not a rare condition and is part of a systemic vasculitis disease. Although ANCA-negative patients have renal and histological characteristics that differ from ANCA-positive patients, renal survival and treatment response in PEGN are independent of ANCA status.

The Software-Defined Networking (SDN) paradigm allows networking hardware to be made “malleable” and remotely manageable by the so-called SDN controllers. However, the current SDN landscape is extremely fragmented. Different open and closed source controller frameworks such as Open-Daylight [1], Ryu [2], Floodlight [3], etc. exist. Porting SDN applications from one such platform to another is practically impossible and so, SDN users like network operators face a situation where they are either confined to applications working for the platform of their choice, or forced to re-implement their solutions every time they encounter a new platform.

Background Accidental transmission of Creutzfeldt-Jakob disease (CJD) has been reported after neurosurgical interventions, use of intracerebral electrodes, corneal transplants, and after the administration of human-derived hormones. Acquired CJD has also been documented after dural grafting with tissues of human cadaver origin. At present, quinacrine and chlorpromazine are being investigated for the treatment of sporadic CJD, with the hope of offering an effective treatment of an otherwise fatal disease. Our objective was to report a case of iatrogenic CJD occurring 18 years after the implant of a dural graft of human origin and to inform on the results of the treatment with quinacrine and chlorpromazine. Case Description In 1984, a 46-year-old woman was given a Lyodura graft for decompression of Chiari I malformation and syringomyelia. The patient was diagnosed with CJD in 2002. In view of the scarce options for treatment of CJD and after reviewing the current literature, the patient was treated with quinacrine and chlorpromazine. She showed no clinical improvement and died 6 months after hospital admission. The iatrogenic origin of the disease in this patient is supported by the clinical features, laboratory data, and findings from the brain necropsy. Conclusions Patients who have received a dural graft of cadaveric origin may be at risk for developing CJD after very prolonged incubation periods. Treatment with quinacrine and chlorpromazine for acquired CJD was ineffective in our patient. A clinical trial on the use of antiprion agents is warranted.

Introducción: La hospitalización afecta a la dinámica de las relaciones familiares y obliga a cambios en la representación de los roles habituales. El papel de los cuidadores familiares adquiere toda su relevancia en la medida que satisfacen las necesidades del enfermo. Esta actividad en la mayoría de los casos es realizada por mujeres. Objetivos: Conocer el perfil y tipo de cuidados que prestan los cuidadores familiares en las unidades de Maxilofacial, Neurología, Neurocirugía y Traumatología del Hospital de Traumatología de Granada. Analizar las necesidades y problemas con los que se encuentran en el hospital. Conocer la opinión del personal de enfermería sobre el cuidador familiar. Diseño: Cualitativo, mediante Observación sistemática, grupos focales (uno con enfermeras y otro con auxiliares), encuestas y entrevistas en profundidad. El análisis de contenido ha sido realizado mediante el soporte informático Atlas/ti, 2.4. Resultados: correspondientes a la categoría de hábitat hospitalario, en relación con las actividades, nivel de información, demandas, etc, de los cuidadores familiares. Conclusiones: El ámbito hospitalario es hostil para el cuidador familiar; es necesario establecer un nuevo marco relacional entre los profesionales y los cuidadores y reconocer su presencia y actividad dentro de la institución sanitaria.Introduction: Generally hospitalization affects familiar relationships and it also obvies to take certain changes in families’ routine. That is why family caregivers have acquired an important role, as they fulfil the needs of the patients. Most of the times, this activity is performed by women. Aims: The aims of this article are: to explain family care givers profile and the kind of care they provide in the following units: Maxilofacial, Neurology, Neurosurgery and Traumatology in the University Hospital Traumatología y Rehabilitación in Granada.This article will analyse different needs and problems family caregivers find within the hospital and inform about nurses opinion concerning the role of family caregivers. Design: A qualitative design has been used by means of systematic observation and focal group. Surveys and in-depth interviews have been carried out within 2 different groups: nurses and auxiliary nurses. The results obtained have been analysed by the programme Atlas/ti 2.4. Results: The results mentioned above were the appropriate for an hospital in relation with family caregivers as far as activities, level of information, and requests are concerned. Conclusion: On the whole atmosphere in hospitals is somehow hostile to family caregivers. For this reason it will be convenient to set up a different kind of professional relations between health staff and family caregivers. Moreover, it is necessary to recognize the importance of family caregivers role in the hospital.

Santa Olalla is a Mediterranean permanent coastal shallow lake, with high annual solar irradiation and warm water temperature throughout the year. Ecosystem metabolism, chlorophyll a concentrations, and physical and chemical features were studied in the Santa Olalla lake from March 1998 to February 2000. Gross primary productivity (GPP) and community respiration (CR) were determined using a modification of the one-station diel oxygen change method. Chlorophyll a, Secchi depth, and total phosphorous and nitrogen reveal Santa Olalla to be a hypereutrophic system. Values of GPP and CR were very high (average 7.88 g O2 m−2 d−1 and 8.52 g O2 m−2 d−1, respectively). Principal components analysis and a multiple regression model showed photosynthetically active radiation and soluble reactive phosphorus to be the main factors that control primary production in Santa Olalla. Also, the annual and interannual variation of water level in Santa Olalla seems to be an important factor that influences the ecological processes of this system. Mean net daily metabolism during a hydrologic period was not statistically different from 0 (0.008 g O2 m−2 d−1, p=0.99), and the average P/R ratio was not statistically different from 1 (1.164, p=0.343). These results suggest that the primary productivity was balanced with community respiration in Santa Olalla lake. The high values of metabolic rates and low nutrient concentrations in this aquatic ecosystem suggest a quick recycling of nutrients, which were assimilated almost instantaneously after mineralization.

We showed previously that exogenous overexpression of C3G, a guanine nucleotide releasing factor (GEF) for Rap1 and R-Ras proteins, blocks the focus-forming activity of cotransfected, activated, sis, ras and v-raf oncogenes in NIH 3T3 cells. In this report, we show that C3G also interferes with dbl and R-Ras focus-forming activity and demonstrate that the transformation suppressor ability of C3G maps to its Crk-binding region (SH3-b domain). Using full-length C3G and C3GACat mutant, lacking catalytic domain, we showed here that overexpression of cotransfected C3G or C3GACat inhibited oncogenic Hras lys12-mediated phosphorylation of ERK, without altering Ras and Raf-1 kinase activation. We also showed that, overexpressed C3G and C3GΔCat inhibited the viability of oncogenic Ras-induced colonies in soft agar, indicating that C3G interferes with the anchorage-independent growth of Ras-transformed cells in a Rap1-independent manner. Consistent with both observations, overexpression of exogenous C3G and C3GΔCat also caused downregulation of Ras-induced cyclin A expression. Altogether, our results indicate that C3G interferes with at least two separate aspects of oncogenic transformation - cell cycle progression and loss of contact inhibition - and that these inhibitory effects probably account for its transformation suppressor activity., This work was supported by grants SAF00-0069 from MCYT and PI021570 from FIS, Spain. CG was supported by the Ramón y Cajal Program from MCYT.

Recently it has been described that dopamine (DA), via dopaminergic type 2 receptors (D2R), activates the mitogen-activated protein kinase extracellular signal-regulated kinase (MAPK/ERK) proteins in alveolar epithelial cells (AEC), which results in the upregulation of Na+-K+-ATPase. In the present report, we used AEC to investigate the signaling pathway that links DA with ERK activation. Incubation of AEC with DA resulted in rapid and transient stimulation of ERK activity, which was mediated by Ras proteins and the serine/threonine kinase Raf-1. Pretreatment of AEC with Src homology 3 binding peptide, which blocks the interaction between Grb2 and Sos, did not prevent DA activation of ERK. Diacylglycerol (DAG)-dependent protein kinase C (PKC) isoenzymes, involved in the DA-mediated activation of ERK proteins as pretreatment with either bisindolylmaleimide or Ro-31-8220, prevented the phosphorylation of Elk-1, and quinpirole, a D2R activator, stimulates the translocation of PKCε. Together, the data suggest that DA activated MAPK/ERK via Ras, Raf-1 kinase, and DAG-dependent PKC isoenzymes, but, importantly and contrary to the classical model, this pathway did not involve the Grb2-Sos complex formation.

The networking research community has started looking into key questions on energy efficiency of communication networks. The European Commission activated under the FP7 the TREND Network of Excellence with the goal of establishing the integration of the EU research community in green networking with a long perspective to consolidate the European leadership in the field. TREND integrates the activities of major European players in networking, including manufacturers, operators, research centers, to quantitatively assess the energy demand of current and future telecom infrastructures, and to design energy-efficient, scalable and sustainable future networks. This paper describes the main results of the TREND research community and concludes with a roadmap describing the next steps for standardization, regulation agencies and research in both academia and industry. The research leading to these results has received funding from the EU 7th Framework Programme (FP7/2007–2013) under Grant Agreement No. 257740 (NoE TREND).

To analyze, in older patients with schizophrenia, the methylation status of a set of genes associated with the pathophysiology of the disorder but including anatomical, clinical, and cognitive criteria in the experimental design that, in conjunction with the epigenetic status of specific genes, allows us to derive an integrative model.This study included 29 human brain samples from older schizophrenic patients with severe and mild cognitive impairment. We administered a comprehensive battery of neurocognitive tests to determine the size of the impairment across different cognitive domains. We focused our study on the analysis of the methylation pattern of 19 genes of major neurotransmitter systems using methylation-specific PCR and bisulfite genomic sequencing.Our results highlight an absence of hypermethylation and hypomethylation in older patients with schizophrenia and in healthy controls, irrespective of the degree of the cognitive deficit measured in the neuropsychological assessment (Fisher's exact test; p0.05).mRNA or protein expression level differences in genes of major neurotransmitter systems that are known to be altered in schizophrenia must be because of regulatory mechanisms other than the DNA methylation of its promoter regions, although our results highlight the idea that the analysis of the epigenetic mechanisms involved in schizophrenia represents a new approach that has the possibility of uncovering molecular mechanisms of dysregulated gene expression in this complex disorder.

Twitter is one of the most popular applications in the current Internet with more than 500 M registered users across the world. In this paper, we conduct a comprehensive analysis to understand the geographical characteristics of Twitter using cross-community mining techniques. Specifically, we study the locality level shown by the three main elements of Twitter, namely users, relationships and information flow. For this purpose, we rely on a dataset including the geolocation information of more than 17, 100 and 3.5 M users, relationships and tweets, respectively. Our main findings are: (1) most of the Twitter users perform their activity from an area of at most few hundred kms covering few cities within a unique country; (2) the location (i.e., country), and in particular factors such as language or Twitter popularity within a country, dictates the level of locality in the relationships of users and Twitter conversations originated in that country. The combination of these factors reveals the presence of four types of country locality profiles that we carefully analyze and compare in the paper.

Santa Olalla and Dulce are two shallow natural eutrophic lakes (lagunas) located in Donana National Park (south of Spain). Both lagunas have high algal biomass and pH and are surrounded by a macrophyte fringe of Juncus spp. and Scirpus spp. The effect of the macroinvertebrate community on decomposition rates (k) of Juncus maritimus was measured in both lagunas using the litter bag method over a one year period after which less than 10% of the original litter bag material remained. Two different mesh sizes, coarse (5 mm) and fine (0.25 mm), were used to evaluate macroinvertebrate community effects on decomposition. Decomposition rates were rapid, with k values of 0.0162 day -1 in coarse bags and 0.0094 day -1 for fine bags at Santa Olalla and 0.0095, 0.0088 day -1 for coarse and fine bags, respectively, at Dulce. Both lagunas had similar densities of macroinvertebrates, with a dominance of shredder-gatherer chironomids. However, densities of scrapers (Ancylidae) increased in Santa Olalla in spring but were almost absent in Dulce. The influence of different physical and chemical parameters and of the macroinvertebrate community on the decomposition process is studied. In spite of some potential confounding effects in the use of fine mesh bags in standing water systems, it is concluded that morphometrical characteristics of the lagunas are important in controlling decomposition rates.

Dopamine (DA) increases lung edema clearance by regulating vectorial Na+transport and Na-K-ATPase in the pulmonary epithelium. We studied the role of the mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK) pathway in the DA regulation of Na-K-ATPase in alveolar epithelial cells (AEC). Incubation of AEC with DA resulted in a rapid stimulation of ERK activity via dopaminergic type 2 receptors. Analysis of total RNA and protein showed a 1.5-fold increase in the Na-K-ATPase β1-subunit mRNA levels and up to a fivefold increase in β1-subunit protein abundance after DA stimulation, which was blocked by the MAPK kinase (MEK) inhibitors PD-98059 and U-0126. Also, the DA-ERK pathway stimulated the synthesis of a green fluorescent protein reporter gene driven by the β1-subunit promoter, which indicates that DA regulates the Na-K-ATPase β1-subunit at the transcriptional level. The DA-mediated increase in β1-subunit mRNA protein resulted in an increase in functional Na pumps in the basolateral membranes of alveolar type II cells. These results suggest that the MAPK-ERK pathway is an important mechanism in the regulation of Na-K-ATPase by DA in the alveolar epithelium.

The efficacy and safety of transjugular liver biopsy used to obtain liver specimens in patients with coagulation disorders have been widely proven. However, histopathologic examination is not always possible because of fragmented samples provided by the aspiration technique. Recently, an automated device with a Tru-Cut-type needle was designed. In this randomized controlled trial, the use of this new device is compared with the traditional method in terms of efficacy and safety.Fifty-six patients were included in the study; 28 were randomized to undergo the aspiration technique and 28 were randomized to undergo the automated biopsy technique.Correct positioning of the device was achieved in 93% of patients undergoing the aspiration technique and 96% of patients undergoing the automated biopsy technique (P = NS). Mean duration of the procedure and total number of passes were significantly higher in the aspiration needle group than in the automated device group (22.6 min +/- 12.6 vs 15.5 min +/- 9.4; P = .03, and 3.3 min +/- 1.9 vs 1.5 min +/- 0.63; P.001, respectively). The number of portal tracts was significantly higher in the automated device group (4.7 +/- 2.5 vs. 2.7 +/- 3.4; P.05). Adequate specimens for histopathologic evaluation were obtained in 26 patients in the automated device group and 24 patients in the aspiration needle group (92.8% vs 85.7%; P = NS), but a definite histopathologic diagnosis was more frequently obtained with the automated biopsy device (68% vs 43%; P = .05). No significant differences were observed in complication rates (7.14% vs. 10.7%; P = NS).The automated biopsy device for transjugular liver biopsy is more effective than an aspiration needle in obtaining good samples for a definite histologic diagnosis.

Fundamento Determinar las tasas de exposicion accidental a patogenos hematicos en los diferentes estamentos del personal sanitario y analizar las caracteristicas y consecuencias de la exposicion. Material y M etodos Se evaluaron los accidentes de exposicion a patogenos hematicos declarados en nuestro centro entre 1996-1999. El protocolo de recogida de datos incluia variables sociodemograficas, caracteristicas de la exposicion, variables en relacion con el estado inmunitario del expuesto y de la fuente de exposicion, y seguimiento serologico del expuesto. Resultados Se declararon 407 exposiciones. El estamento con mayor tasa de exposicion ocupacional fue enfermeria (61,6%). El pinchazo fue el tipo de accidente mas frecuente (84,8%), siendo la salpicadura responsable del 15,2% restante. En el 14,5% de los accidentes existia riesgo de transmision de al menos un patogeno hematico. Al analizar por estamentos la tasa de exposicion con fuente de infeccion positiva observamos que el personal medico fue el mas frecuentemente implicado (28,3%), seguido de enfermeria (13,9%) y auxiliares de enfermeria (8%). En los accidentes por salpicadura la tasa de exposicion con fuente positiva fue mayor que en los accidentes punzantes (33,8% frente a 13,3%) y, sin embargo, en ninguno de ellos se habian tomado medidas de barrera. No se documento ningun caso de transmision al personal sanitario. Conclusiones Aunque la enfermeria es el estamento con mayor tasa de accidentes de exposicion a patogenos hematicos, el personal medico es el que presenta una mayor tasa de exposicion con fuente positiva. No se utilizan adecuadamente las medidas de barrera, sobre todo en los accidentes producidos por salpicaduras

International audience; We study the problem of reducing power consump- tion in an Internet Service Provider (ISP) network by designing the content distribution infrastructure managed by the operator. We propose an algorithm to optimally decide where to cache the content inside the ISP network. We evaluate our solution over two case studies driven by operators feedback. Results show that the energy-efficient design of the content infrastructure brings substantial savings, both in terms of energy and in terms of bandwidth required at the peering point of the operator. Moreover, we study the impact of the content characteristics and the power consumption models. Finally, we derive some insights for the design of future energy-aware networks.

The mammalian sos1 and sos2 genes encode highly homologous members of the Son-of-sevenless family of guanine nucleotide exchange factors. They are ubiquitously expressed and play key roles in transmission of signals initiated by surface protein tyrosine kinases that are transduced into the cell through the action of membrane-associated Ras proteins. Recent reports showed that targeted disruption of the sos1 locus results in embryonic lethality. To gain insight into the in vivo function of sos2, we disrupted its catalytic CDC25-H domain by means of gene targeting techniques. Mating among heterozygous sos2(+/-) mice produced viable sos2(-/-) offspring with a normal Mendelian pattern of inheritance, indicating that the loss of sos2 does not interfere with embryo viability in the uterus. Adult homozygous mutant sos2(-/-) mice reached sexual maturity at the same age as their wild-type littermates, and both male and female null mutants were fertile. Histopathological analysis showed no observable differences between mutant and wild-type mice. Our results show that unlike the case for sos1, sos2 gene function is dispensable for normal mouse development, growth, and fertility.

We previously reported that lung edema clearance was stimulated by dopamine (DA). The purpose of this study was to determine whether the DA-mediated stimulation of edema clearance occurs via an adrenergic or dopaminergic regulation of alveolar epithelial Na, K-ATPase. When isolated perfused rat lungs were coinstilled with DA and SCH 23390 (a specific D(1) receptor antagonist), there was a dose-dependent attenuation of the stimulatory effects of DA. Coinstillation with S-sulpiride (a specific D(2) receptor antagonist) or propranolol (a beta-adrenergic antagonist) did not alter DA-stimulated clearance. Similarly, the specific dopaminergic D(1) agonist fenoldopam increased lung edema clearance, but quinpirole (a specific dopaminergic D(2) agonist) did not. (125)I-SCH 23982 binding studies suggested that D(1) receptors are expressed on alveolar type II (ATII) cells with an apparent dissociation constant (K(d)) of 4.4 nM and binding maximum (Bmax) 9.8 pmol/mg. Consistent with these results, the D(1) receptor messenger RNA (mRNA) and protein were detected in ATII cells by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. These data demonstrate a novel mechanism involving the activation of dopaminergic D(1) receptors which mediates DA-stimulated edema removal from rat lungs.

Two human hSos1 isoforms (Isf I and Isf II; Rojas et al., Oncogene 12, 2291-2300, 1996) defined by the presence of a distinct 15 amino acid stretch in one of them, were compared biologically and biochemically using representative NIH3T3 transfectants overexpressing either one. We showed that hSos1-Isf II is significantly more effective than hSos1-Isf I to induce proliferation or malignant transformation of rodent fibroblasts when transfected alone or in conjunction with normal H-Ras (Gly12). The hSos1-Isf II-Ras cotransfectants consistently exhibited higher saturation density, lower cell-doubling times, increased focus-forming activity and higher ability to grow on semisolid medium and at low serum concentration than their hSos1-Isf I-Ras counterparts. Furthermore, the ratio of GTP/GDP bound to cellular p21ras was consistently higher in the hSos1-Isf II-transfected clones, both under basal and stimulated conditions. However, no significant differences were detected in vivo between Isf I- and Isf II-transfected clones regarding the amount, stability and subcellular localization of Sos1-Grb2 complex, or the level of hSos1 phosphorylation upon cellular stimulation. Interestingly, direct Ras guanine nucleotide exchange activity assays in cellular lysates showed that Isf II transfectants consistently exhibited about threefold higher activity than Isf I transfectants under basal, unstimulated conditions. Microinjection into Xenopus oocytes of purified peptides corresponding to the C-terminal region of both isoforms (encompassing the 15 amino acid insertion area and the first Grb2-binding motif) showed that only the Isf II peptide, but not its corresponding Isf I peptide, was able to induce measurable rates of meiotic maturation, and synergyzed with insulin, but not progesterone, in induction of GVBD. Our results suggest that the increased biological potency displayed by hSos1-Isf II is due to higher intrinsic guanine nucleotide exchange activity conferred upon this isoform by the 15 a.a. insertion located in proximity to its Grb2 binding region.

Ventilator-associated lung injury (VALI) is caused by high tidal volume (VT) excursions producing microvascular leakage and pulmonary edema. However, the effects of VALI on lung edema clearance and alveolar epithelial cells' Na,K-ATPase function have not been elucidated. We studied lung edema clearance in the isolated-perfused rat lung model after ventilation for 25, 40, and 60 min with high VT (peak airway opening pressure [Pao] of approximately 35 cm H2O) and compared them with low VT ventilation (Pao approximately 8 cm H2O), moderate VT ventilation (Pao approximately 20 cm H2O), and nonventilated rats. Lung edema clearance in control rats was 0.50 +/- 0.02 ml/h and decreased after 40 and 60 min of high VT to 0.26 +/- 0.03 and 0.11 +/- 0.08 ml/h, respectively (p < 0.01), but did not change after low VT and moderate VT ventilation at any time point. Lung permeability to small (22Na+, [3H]mannitol) and large solutes (fluorescein isothiocyanate-tagged albumin [FITC-albumin]) increased significantly in rats ventilated for 60 min with high VT, compared with low VT, moderate VT, and control rats (p < 0.01). Paralleling the impairment in lung edema clearance we found a decrease in Na,K-ATPase activity in alveolar type II (ATII) cells isolated from rats ventilated with moderate VT and high VT for 40 min without changes in alpha1 Na,K-ATPase mRNA. We reason that VALI decreases lung ability to clear edema by inhibiting active sodium transport and Na,K-ATPase function in the alveolar epithelium.

Alzheimer's disease (AD) is the most frequent degenerative dementia in our setting. In most patients the initial manifestations of the disease consist in a selective and progressive compromise of memory. Yet, it is not a homogeneous process and in some cases the mode of presentation can be atypical. The presentation of AD in the form of an early disorder affecting personality, behaviour and the executive functions has been called the frontal variant of AD. In our case, its definitive diagnosis was only possible by means of a histological analysis, given the fact that the applicable clinical criteria were then insufficient to reach a diagnosis of this atypical form of AD.We report the cases of two patients, one female and one male aged 60 and 52 respectively, who presented a progressive picture of cognitive impairment with initial involvement of the executive functions and personality changes, together with mood disorders. As a result, the initial diagnosis was one of probable frontotemporal dementia. However, in both cases, the autopsy revealed data consistent with a diagnosis of AD, with a distribution of the pathology that essentially affected the frontal lobes.AD has a heterogeneous form of presentation, which can give rise to errors in its initial diagnosis, since current clinical criteria do not take this clinical variability sufficiently into account. We therefore consider it important to pay attention to the atypical forms of AD with the aim of developing new diagnostic methods that allow AD to be distinguished from other degenerative processes.Variante frontal de la enfermedad de Alzheimer. Dos casos confirmados anatomopatologicamente y revision de la bibliografia.Introduccion. La enfermedad de Alzheimer (EA) es la causa mas frecuente de demencia en nuestro medio. En la mayoria de los pacientes, las manifestaciones iniciales consisten en una afectacion selectiva y progresiva de la memoria. Sin embargo, no se trata de un proceso homogeneo y, en algunos casos, el modo de presentacion puede ser atipico. La presentacion de la EA en forma de alteracion precoz de la personalidad, el comportamiento y las funciones ejecutivas se ha denominado variante frontal de la EA. En nuestro caso, su diagnostico definitivo solo fue posible mediante el estudio histologico, pues los criterios clinicos vigentes resultaron entonces insuficientes para el diagnostico de esta forma atipica de la EA. Casos clinicos. Dos pacientes, una mujer y un hombre de 60 y 52 años respectivamente, presentaron un cuadro progresivo de deterioro cognitivo con afectacion inicial de las funciones ejecutivas y cambio de personalidad, junto con alteraciones del estado de animo, por lo que se realizo el diagnostico inicial de probable demencia frontotemporal. No obstante, en ambos casos, la autopsia revelo datos compatibles con el diagnostico de EA, con una distribucion de la patologia que afectaba fundamentalmente a los lobulos frontales. Conclusiones. La EA tiene una forma heterogenea de presentacion, lo que puede originar errores en su diagnostico inicial, dado que los criterios clinicos actuales no recogen de modo suficiente esta variabilidad clinica. Por ello, consideramos importante prestar atencion a las formas atipicas de la EA con el objeto de desarrollar nuevos metodos diagnosticos que permitan diferenciar la EA del resto de procesos degenerativos.

Aimed at answering important questions about the energy demand of current telecom infrastructure and the design of sustainable and energy-efficient future networks, the research of a number of European partners is brought together in the TREND project. In this paper we present the achievements of the Work Package coordinating the experimental activities of the project - WP4. Although not presenting a completely finished portrait yet, the results shown help building a better global view on the “big picture” in the field of energy-efficient networking.

Post-transplant complications.-- et al., Transplantation-associated thrombotic microangiopathy (TA-TMA) is a feared complication of allogeneic hematopoietic SCT (HSCT) owing to its high mortality rate. The use of calcineurin inhibitors or sirolimus (SIR) for GVHD prophylaxis has been suggested as a potential risk factor. However, the impact of tacrolimus (TAC) and SIR combinations on the increased risk of TA-TMA is currently not well defined. We retrospectively analyzed the incidence of TA-TMA in 102 allogeneic HSCT recipients who consecutively received TAC plus SIR (TAC/SIR) (n=68) or plus MTX (TAC/MTX)±ATG (n=34) for GVHD prophylaxis. No significant differences were observed in the incidence of TA-TMA between patients receiving TAC/SIR vs TAC/MTX±ATG (7.4% vs 8.8%, P=0.8). Only grade III-IV acute GVHD, previous HSCT and serum levels of TAC >25 ng/mL were associated with a greater risk of TA-TMA. Patients developing TA-TMA have significantly poorer survival (P

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License., [Background]: Previous studies by our group and others have shown that C3G interacts with Bcr-Abl through its SH3-b domain. [Results]: In this work we show that C3G and Bcr-Abl form complexes with the focal adhesion (FA) proteins CrkL, p130Cas, Cbl and Abi1 through SH3/SH3-b interactions. The association between C3G and Bcr-Abl decreased upon Abi1 or p130Cas knock-down in K562 cells, which suggests that Abi1 and p130Cas are essential partners in this interaction. On the other hand, C3G, Abi1 or Cbl knock-down impaired adhesion to fibronectin, while p130Cas silencing enhanced it. C3G, Cbl and p130Cas-SH3-b domains interact directly with common proteins involved in the regulation of cell adhesion and migration. Immunoprecipitation and immunofluorescence studies revealed that C3G form complexes with the FA proteins paxillin and FAK and their phosphorylated forms. Additionally, C3G, Abi1, Cbl and p130Cas regulate the expression and phosphorylation of paxillin and FAK. p38α MAPK also participates in the regulation of adhesion in chronic myeloid leukemia cells. It interacts with C3G, CrkL, FAK and paxillin and regulates the expression of paxillin, CrkL and α5 integrin, as well as paxillin phosphorylation. Moreover, double knock-down of C3G/p38α decreased adhesion to fibronectin, similarly to the single silencing of one of these genes, either C3G or p38α. These suggest that C3G and p38α MAPK are acting through a common pathway to regulate cell adhesion in K562 cells, as previously described for the regulation of apoptosis. [Conclusions]: Our results indicate that C3G-p38αMAPK pathway regulates K562 cell adhesion through the interaction with FA proteins and Bcr-Abl, modulating the formation of different protein complexes at FA., This work was supported by grants form the Spanish Ministry of Health (ISCIII) [FIS-PI070078 to CG and FIS-PI070071 to AP], by grants from the Spanish Ministry of Economy and Competitiveness [SAF2010-20918-C02-02 to CG, SAF2010-20918-C02-01 to AP and BFU2009‐08389 to JMP], by a grant for Research in Biomedicine from the Council of Health and Social Welfare of Junta de Castilla y León and by grants from the Council of Education of Junta de Castilla y León [CSI06A09 and SA157A12-1], Spain (to JMP and CG). All funding was cosponsored by the European FEDER Program.

This is an open-access paper.-- et al., Allogeneic hematopoietic stem cell transplantation recipients have an increasing risk of both hemorrhagic and thrombotic complications. However, the competing risks of two of these life-threatening complications in these complex patients have still not been well defined. We retrospectively analyzed data from 431 allogeneic transplantation recipients to identify the incidence, risk factors and mortality due to thrombosis and bleeding. Significant clinical bleeding was more frequent than symptomatic thrombosis. The cumulative incidence of a bleeding episode was 30.2% at 14 years. The cumulative incidence of a venous or arterial thrombosis at 14 years was 11.8% and 4.1%, respectively. The analysis of competing factors for venous thrombosis revealed extensive chronic graft-versus-host disease to be the only independent prognostic risk factor. By contrast, six factors were associated with an increased risk of bleeding; advanced disease, ablative conditioning regimen, umbilical cord blood transplantation, anticoagulation, acute III-IV graft-versus-host disease, and transplant-associated microangiopathy. The development of thrombosis did not significantly affect overall survival (P=0.856). However, significant clinical bleeding was associated with inferior survival (P

et al., Hepatocyte growth factor (HGF) and its receptor, Met, are key determinants of distinct developmental processes. Although HGF exerts cardio-protective effects in a number of cardiac pathologies, it remains unknown whether HGF/Met signaling is essential for myocardial development and/or physiological function in adulthood. We therefore investigated the requirement of HGF/Met signaling in cardiomyocyte for embryonic and postnatal heart development and function by conditional inactivation of the Met receptor in cardiomyocytes using the Cre-α-MHC mouse line (referred to as α-MHCMet-KO). Although α-MHCMet-KO mice showed normal heart development and were viable and fertile, by 6. months of age, males developed cardiomyocyte hypertrophy, associated with interstitial fibrosis. A significant upregulation in markers of myocardial damage, such as β-MHC and ANF, was also observed. By the age of 9. months, α-MHCMet-KO males displayed systolic cardiac dysfunction. Mechanistically, we provide evidence of a severe imbalance in the antioxidant defenses in α-MHCMet-KO hearts involving a reduced expression and activity of catalase and superoxide dismutase, with consequent reactive oxygen species accumulation. Similar anomalies were observed in females, although with a slower kinetics. We also found that Met signaling down-regulation leads to an increase in TGF-β production and a decrease in p38MAPK activation, which may contribute to phenotypic alterations displayed in α-MHCMet-KO mice. Consistently, we show that HGF acts through p38α to upregulate antioxidant enzymes in cardiomyocytes. Our results highlight that HGF/Met signaling in cardiomyocytes plays a physiological cardio-protective role in adult mice by acting as an endogenous regulator of heart function through oxidative stress control., This work was supported by grants: (AFM)-13683 from Association Française contre les myopathies, France, FIS-PI07/0071 and SAF-2010-20198-C02-01 from Ministry of Science and Innovation, Spain, and grants from Comunidad de Madrid/Universidad Complutense de Madrid: CAM/UCM 920384 and UCM-BSCH 920384, Spain to A.P.; BFU2011-25304 from Ministry of Science and Innovation, Spain, RD12/0019/0022 (TerCel network, ISCIII), P11-CTS-7564 (Junta de Andalucía) to R. M.-Ch.; FRM (Fondation pour la Recherche Médicale), Fondation Bettencourt-Schueller, and Association Française contre les myopathies (AFM) to F.M.; SAF2010-15881 from Ministry of Science and Innovation, Spain, and RD012/0021 (RedinRen network, ISCIII), and GR100 (Junta de Castilla y León) to J.M. L.-N. The cardiovascular phenotyping unit of the University of Salamanca, including the telemetry equipment, has been acquired with the support of the European Regional Development Funds (FEDER).

A 6.5 kb DNA fragment containing the gene (thrC) encoding threonine synthase, the last enzyme of the threonine biosynthetic pathway, has been cloned from the DNA ofBacillus sp. ULM1 by complementation ofEscherichia coli andBrevibacterium lactofermentum thrC auxotrophs. Complementation studies showed that thethrB gene (encoding homoserine kinase) is found downstream from thethrC gene, and analysis of nucleotide sequences indicated that thehom gene (encoding homoserine dehydrogenase) is located upstream of thethrC gene. The organization of this cluster of genes is similar to theBacillus subtilis threonine operon (hom—thrC—thrB). An 1.9 kbBclI, fragment from theBacillus sp. ULM1 DNA insert that complementedthrC mutations both inE. coli and in corynebacteria was sequenced, and an ORF encoding a protein of 351 amino acids was found corresponding to a protein of 37462 Da. ThethrC gene showed a low G+C content (39.4%) and the encoded threonine synthase is very similar to theB. subtilis enzyme. Expression of the 1.9 kbBclI DNA fragment inE. coli minicells resulted in the formation of a 37 kDa protein. The upstream region of this gene shows promoter activity inE. coli but not in corynebacteria. A peptide sequence, including a lysine that is known to bind the pyridoxal phosphate cofactor, is conserved in all threonine synthase sequences and also in the threonine and serine dehydratase genes. Amino acid comparison of nine threonine synthases revealed evolutionary relationships between different groups of bacteria.

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.

ResumenSe describen 2 casos de niños con fisura labiopalatina unilateral total con gran separación de procesos alveolares, remitidos a nuestra unidad. Tras valoración por el equipo multidisciplinar se procede a realizar tratamiento ortopédico mediante moldeamiento nasoalveolar prequirúrgico durante 3,5 meses en un caso y 2 meses en el otro. A los 9 meses se mantiene la coalescencia de ambos procesos alveolares y la simetría nasal en ambos pacientes, existiendo una buena proyección de la punta nasal y longitud de la columela.AbstractWe present two cases of children with total unilateral cleft lip and palate with a marked separation of alveolar segments. After evaluation by a multidisciplinart team, he children were treated with a presurgical nasoalveolar moulding for 2 months in one of them and 3.5 months in the other. At 9 months after the presurgical nasoalveolar moulding treatment, there was improved dental arch form, the cleft edges moved closer to each other, and improved symmetry of the nose in width, height, and columella lengths in both patients.

et al., [Background]: Few studies have evaluated the risk of pregnancy-related adverse events in asymptomatic relatives of probands for VTE and factor V Leiden or the G20210A variant. The antepartum management of this population ranges from antepartum anticoagulation therapy to clinical surveillance. [Objective]: To evaluate the risk of placenta-mediated pregnancy complications and pregnancy-related VTE in VTE-asymptomatic families of probands with VTE and who are heterozygous carriers of either factor V Leiden or PT-G20210A mutation. [Methods]: One hundred and fifty-eight relatives, who had 415 pregnancies, were retrospectively evaluated. Odds ratios and 95% confidence intervals were calculated to compare pregnancy outcomes between women with and without thrombophilia. [Results]: In the factor V Leiden group, 22 placenta-mediated pregnancy events of 152 pregnancies (14.4%) were reported, compared with 25 adverse events of 172 pregnancies in the G20210A prothrombin group (14.5%) and 13 adverse events of 91 pregnancies in the non-carrier group (14.2%). Carriers of factor V Leiden or G20210A prothrombin were not associated with a higher risk of pregnancy-adverse outcomes compared with non-carriers: OR 1.02 (95% CI, 0.40-2.25) and 1.25 (95% CI, 0.48-3.24), respectively. Four episodes of pregnancy-associated VTE of 415 pregnancies (0.96%) were recorded. Two episodes of VTE in the G20210A group, one in the factor V Leiden group, and one episode in the non-carrier group were noted. [Conclusions]: In VTE-asymptomatic relatives of probands with VTE, the presence of factor V Leiden or the G20210A prothrombin mutation in heterozygosis should not lead to a decision to instigate antepartum prophylaxis.

OBJECTIVE: To evaluate the efficacy of an educational program for the prevention of catheter colonization. DESIGN: Two cross-sectional studies were carried out in a 500-bed randomly selected area of the hospital, separated by an educational program on the care of intravenous lines based on the Centers for Disease Control and Prevention (CDC) recommendations for the control of catheter-related infections. SETTING: A 2,100-bed urban general hospital affiliated with the University of Madrid (Spain). METHODS: Characteristics of patients and catheters and appropriateness of catheter care were evaluated. Cultures were taken from the point of insertion of the vascular catheter, the hubs, and infusion fluids. When catheter-associated infection was suspected, the distal end of the catheter was sent for culture and two blood cultures were taken. We compared the clinical and microbiological data before and after carrying out an educational program based on CDC recommendations for the control of catheter-related infections. RESULTS: Characteristics of patients and catheters did not differ between the two cross-sectional studies. Compared with baseline data, after the educational program we observed a reduction of inappropriate catheter care, from 83% to 38% (45% difference, 95% confidence interval [CI95], 55% to 35%, P < 0.0000), and a reduction in the rate of skin colonization, from 34% to 18% (16% difference, CI95, 26% to 5%, P < 0.001). The frequency of phlebitis (15% versus 14%), hub colonizations (12% versus 11%), catheter colonizations (2% versus 1%), and catheter-related bacteremias (0% versus 0%) remained unchanged between the two cross-sectional studies. CONCLUSIONS: Our educational program improved catheter care and reduced significantly the proportion of skin colonization around the insertion point. However, the educational program did not modify the proportion of hub colonization; because hub colonization has been demonstrated to be a source of line sepsis, our data suggest the need for a specific program directed to the maintenance of catheter hubs.

A cloned 9.6-kb fragment of Brevibacterium lactofermentum DNA, carrying the entire trp operon and upstream regulatory sequences, produces a polycistronic 7.0-kb transcript as detected by hybridization with an internal probe. The transcription start point ( tsp ) was identified by S1 mapping. The operator-promoter (OP) region subcloned in Escherichia coli and B. lactofermentum promoter-probe vectors exhibited about tenfold higher activity in B. lactofermentum . A 14-bp wild-type (wt) palindrome located at bp −15 to −28 was mutated to change the conserved adenine adjacent to the axis of symmetry. The wt and mutated OP regions were coupled to the amy reporter gene (encoding α-amylase [Amy]) or to the 5′ region ( trpE and trpG genes) of the trp operon, for expression studies. Constructions with the regulatory signals coupled to the wt trpE-trpG genes were introduced in a B. lactofermentum trpE mutant (obtained by gene disruption). The mutation in the palindrome did not affect the promoter activity in B. lactofermentum or E. coli when grown in minimal medium. Tryptophan repressed the OP as assayed by the anthranilate synthase (AS) activity in B. lactofermentum in constructions with the wt OP region, but surprisingly, caused a large stimulation of either AS or the Amy reporter activity, in constructions with the mutated OP . The palindromic sequence is, therefore, involved in a dual repression-stimulation control of expression of the trp operon.