Estimation of electronic coupling in π -stacked donor-bridge-acceptor systems: correction of the two-state model

Comparison of donor-acceptor electronic couplings calculated within two-state and three-state models suggests that the two-state treatment can provide unreliable estimates of Vda because of neglecting the multistate effects. We show that in most cases accurate values of the electronic coupling in a π stack, where donor and acceptor are separated by a bridging unit, can be obtained as Ṽ da = (E2 - E1) μ12 Rda + (2 E3 - E1 - E2) 2 μ13 μ23 Rda2, where E1, E2, and E3 are adiabatic energies of the ground, charge-transfer, and bridge states, respectively, μij is the transition dipole moments between the states i and j, and Rda is the distance between the planes of donor and acceptor. In this expression based on the generalized Mulliken-Hush approach, the first term corresponds to the coupling derived within a two-state model, whereas the second term is the superexchange correction accounting for the bridge effect. The formula is extended to bridges consisting of several subunits. The influence of the donor-acceptor energy mismatch on the excess charge distribution, adiabatic dipole and transition moments, and electronic couplings is examined. A diagnostic is developed to determine whether the two-state approach can be applied. Based on numerical results, we showed that the superexchange correction considerably improves estimates of the donor-acceptor coupling derived within a two-state approach. In most cases when the two-state scheme fails, the formula gives reliable results which are in good agreement (within 5%) with the data of the three-state generalized Mulliken-Hush model

Adenovirus-mediated gene transfer into selected liver segments using a vascular exclusion technique.

Adenovirus-mediated gene therapy is hampered by severe virus-related toxicity, especially to the liver. The aim of the present study was to test the ability of a vascular exclusion technique to achieve transgene expression within selected liver segments, thus minimizing both viral and transgene product toxicity to the liver. An E1-E3-deleted replication-deficient adenovirus expressing a green fluorescent protein (GFP) reporter gene was injected into the portal vein of BDIX rats, with simultaneous clamping of the portal vein tributaries to liver segments II, III, IV, V, and VIII. GFP expression and inflammatory infiltrate were measured in the different segments of the liver and compared with those of the livers of animals receiving the viral vector in the portal vein without clamping. The GFP expression was significantly higher in the selectively perfused segments of the liver as compared with the non-perfused segments (p < 0.0001) and with the livers of animals that received the vector in the portal vein without clamping (p < 0.0001). Accordingly, the inflammatory infiltrate was more intense in the selectively perfused liver segments as compared with all other groups (p < 0.0001). Fluorescence was absent in lungs and kidneys and minimal in spleen. The clinical usefulness of adenovirus-mediated gene transfer to the liver largely depends on the reduction of its liver toxicity. Clamping of selected portal vein branches during injection allows for delivery of genes of interest to targeted liver segments. Transgene expression confined to selected liver segments may be useful in the treatment of focal liver diseases, including metastases.

Revisão sistemática sobre aventais cirúrgicos no controle da contaminação/infecção do sítio cirúrgico

O avental cirúrgico é confeccionado com materiais de tecido e não-tecido. O estudo teve como objetivo verificar se há evidências científicas, pela revisão sistemática, que fundamentem a prática do uso de aventais em cirurgias, conforme seu material de confecção. Consideraram-se estudos básicos de intervenção, que investigaram a contaminação e ou a infecção do sítio cirúrgico com uso de aventais cirúrgicos reutilizáveis e ou de uso-único, utilizando como população pessoas submetidas a cirurgias, em situações reais ou simuladas, em qualquer período, sem limitação de idioma. Para localizar os estudos, utilizou-se estratégia de busca nas bases de dados eletrônicas. Constata-se, com isso, dificuldade de isolar o objeto de intervenção de outros inúmeros fatores que podem interferir nos desfechos, em estudos desta natureza. Dois estudos (E1, E2) obtiveram forte evidência de recomendação, concluindo pela não diferença de contaminação e infecção do sítio cirúrgico entre aventais e campos de tecido e não-tecido.

Hepatitis C virus proteins: from structure to function.

Great progress has been made over the past years in elucidating the structure and function of the hepatitis C virus (HCV) proteins, most of which are now actively being pursued as antiviral targets. The structural proteins, which form the viral particle, include the core protein and the envelope glycoproteins E1 and E2. The nonstructural proteins include the p7 viroporin, the NS2 protease, the NS3-4A complex harboring protease and NTPase/RNA helicase activities, the NS4B and NS5A proteins, and the NS5B RNA-dependent RNA polymerase. NS4B is a master organizer of replication complex formation while NS5A is a zinc-containing phosphoprotein involved in the regulation of HCV RNA replication versus particle production. Core to NS2 make up the assembly module while NS3 to NS5B represent the replication module (replicase). However, HCV proteins exert multiple functions during the viral life cycle, and these may be governed by different structural conformations and/or interactions with viral and/or cellular partners. Remarkably, each viral protein is anchored to intracellular membranes via specific determinants that are essential to protein function in the cell. This review summarizes current knowledge of the structure and function of the HCV proteins and highlights recent advances in the field.

Vers une conception intégrative de la dépression du sujet âgé : structure cérébrale, cognition et personnalité

Contexte : la prévalence des épisodes dépressifs majeurs parmi la population âgée générale est de 1-4%. Plusieurs études proposent la dissociation entre la dépression à début tardive (late onset depression, LOD), plus souvent associée à des déficits neuropsychologiques, des lésions cérébrales et des facteurs de risque cardio-vasculaire, et la dépression à début précoce (early onset depression, EOD) associée, elle, aux facteurs génétiques et à certains profiles de personnalité. Toutefois, aucune étude transversale ou longitudinale n'a jusqu'à maintenant mesuré et comparé de façon concomitante les profiles cognitifs, la neuro-imagerie (IRM) et les profiles de personnalité des patients âgés LOD et EOD euthymiques. Méthodes : ce travail se base sur une étude menée par différents services des Hôpitaux Universitaires de Genève (HUG) et du Centre Hospitalier Universitaire Vaudois (CHUV) qui ont collaboré afin de recruter le collectif de patients dépressifs nécessaire. La partie expérimentale est divisée en deux parties. La première, transversale, compare 30 EOD, 11 LOD et 30 sujets contrôles, puis 38 EOD à 62 sujets contrôles. Une évaluation neuropsychologique, des évaluations des lésions et volumes cérébraux à l'IRM, ainsi que des traits de personnalité ont été effectuées. La deuxième partie, longitudinale, évalue sur 2 ans 28 patients EOD à 48 sujets contrôles avec les mêmes outils. Résultats : lors de la première partie, transversale, les performances cognitives et les volumes cérébraux sont préservés chez les patients EOD, alors que les patients LOD présentent une réduction significative de la mémoire épisodique et un taux plus élevé de lésions cérébrales périventriculaires (hyperintensités de la matière blanche) en comparaison avec les patients EOD et les sujets contrôles. Au niveau des traits de personnalité, les patients EOD sont associés à un niveau élevé de Névrosisme, en particulier les facettes Anxiété (N1) et Dépression (N3) mais diminué d'Extraversion, en particulier les facettes Chaleur (E1) et Emotions positives (E6). Dans la seconde partie, longitudinale, les performances cognitives et les volumes cérébraux des patients EOD sont restés, après les 2 ans de suivi (follow-up) comparables aux sujets contrôles. Les niveaux élevés du Névrosisme et sa facette Anxiété (N1) constatés au baseline diminuèrent pour atteindre un niveau normal. Les niveaux diminués des facettes Chaleur (E1) et Emotions positives (E6) au baseline ne persistèrent pas non plus. Seule la facette Dépression (N3) est restée chez les patients EOD significativement plus élevée que chez les sujets contrôles après les 2 ans de suivi. Conclusion : nos résultats supportent la dissociation entre EOD, associée à des facteurs génétiques et psychosociaux, et LOD associée aux facteurs de risque et comorbidités cardio-vasculaires. Après rémission d'un épisode dépressif aigu, les performances cognitives ainsi que les volumes cérébraux des patients EOD restent intactes au long terme, alors que le patient LOD garde des lésions cérébrales ainsi que des atteintes au niveau de la mémoire épisodique. Au niveau de la personnalité, la facette Dépression (N3) du domaine Névrosisme, connu pour être un facteur de risque de dépression, reste une caractéristique bien présente chez le patient EOD.

Double-bundle transtibial posterior cruciate ligament reconstruction with a tendon-patellar bone-semitendinosus tendon autograft: clinical results with a minimum of 2 years' follow-up.

PURPOSE: The purpose of this study was to evaluate the clinical and subjective outcomes after arthroscopic-assisted double-bundle posterior cruciate ligament (PCL) reconstruction. METHODS: A series of 15 patients with grade III isolated chronic PCL tears underwent double-bundle PCL reconstruction. Of these patients, 8 (53%) had simultaneous fractures. The mean time from accident to surgery was 10.8 months (range, 8 to 15 months). The mean age at the time of surgery was 28.2 years (range, 17 to 43 years). All of the patients reported knee insecurity during activities of daily living or light sporting activities, with associated anterior knee pain in 5 patients. Preoperatively, posterolateral or posteromedial corner injuries were ruled out through accurate clinical examination. The knees were assessed before surgery and at a mean follow-up of 3.2 years (range, 2 to 5 years) with a physical examination, 4 different rating scales, and stress radiographs obtained with a Telos device (Telos, Marburg, Germany). RESULTS: Postoperative physical examination revealed a reduction of the posterior drawer and tibial step-off in all cases, although the posterior laxity was not completely normalized. Nevertheless, the patients were subjectively better after surgery. The subjective International Knee Documentation Committee score was significantly ameliorated. With regard to the objective International Knee Documentation Committee score, 6 knees (40%) were graded as abnormal because of posterior displacement of 6 mm or greater on follow-up stress radiographs with the Telos device. On the Lysholm knee scoring scale, the score was excellent in 13% of patients and good in 87%. The mean score on the Hospital for Special Surgery knee ligament rating scale was 85.8. The Tegner activity score showed an amelioration after surgery, but no patient resumed his or her preinjury level of activities. The postoperative stress radiographs revealed an improvement in posterior instability of 50% or more in all but 3 knees (20%). CONCLUSIONS: Our technique of double-bundle PCL reconstruction produced a significant reduction in knee symptoms and allowed the patients to return to moderate or strenuous activity, although the posterior tibial translation was not completely normalized and our results appear to be no better than the results of single-bundle PCL reconstruction. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Ischemic cecal perforation secondary to ESWL of junctional stone in ureterosigmoidostomy (Mainz Pouch II).

We report an unusual case of ischemic cecal perforation after extracorporeal shock wave lithotripsy for an impacted stone at the distal end of the right ureter of a ureterosigmoidostomy in a 78-year-old female patient.

Tigecycline in combination with other antimicrobials: a review of in vitro, animal and case report studies.

Tigecycline has been investigated in combination with other antibacterials against a wide range of susceptible and multiresistant Gram-positive and Gram-negative bacteria. Combinations have been analysed in vitro, in animal models and in human case reports. In vitro, tigecycline combined with other antimicrobials produces primarily an indifferent response (neither synergy nor antagonism). Nevertheless, synergy occurred when tigecycline was combined with rifampicin against 64-100% of Enterococcus spp., Streptococcus pneumoniae, Enterobacter spp. and Brucella melitensis isolates. Combinations of tigecycline with amikacin also showed synergy for 40-100% of Enterobacter spp., Klebsiella pneumoniae, Proteus spp. and Stenotrophomonas maltophilia isolates. Moreover, bactericidal synergisms occurred with tigecycline plus amikacin against problematic Acinetobacter baumannii and Proteus vulgaris, and with colistin against K. pneumoniae. Data from animal experiments and case reports, although limited, displayed consistent beneficial activity of tigecycline in combination with other antibacterials against multiresistant organisms, including vancomycin against penicillin-resistant S. pneumoniae in experimental meningitis, gentamicin against Pseudomonas aeruginosa in experimental pneumonia, daptomycin against Enterococcus faecium endocarditis, and colistin against K. pneumoniae bacteraemia and P. aeruginosa osteomyelitis. Antagonism was extremely rare in vitro and was not reported in vivo. Thus, tigecycline may be combined with a second antimicrobial as part of a combination regimen.

Lésions iatrogènes des voies biliaires lors de la cholécystectomie laparoscopique

Objective: Laparoscopic cholecystectomy (LC) has become the gold standard in the treatment of symptomatic cholelithiasis. The aim of this study was to determine the frequency of occurrence and risk factors of iatrogenic bile duct injuries (IBDI) in the LC and study their treatment modalities. Methods: Between January 2000 and December 2011, a series of 13 patients (6 men, 7 women, mean age 66.7 years, mean BMI 27.9 kg/m2) underwent IBDI in our institution for 2'840 LC performed. These patients were identified retrospectively using a wide range of classification codes in our medical center for archiving. Their medical records were examined individually to identify a IBDI. Results: The frequency of IBDI was 0.46% (n=13). The most common indication for surgery was acute cholecystitis (69.2%). The main cause was the confusion of the common bile duct with the cystic duct in 38.5% of cases. Strasberg classification applied to our sample identified the following injuries: A (n=4), D (n=4), E1 (n=3) and E5 (n=2). They were diagnosed intraoperatively in 46.2% of cases and postoperatively in 53.8% of cases. The rate of type D lesions was significantly higher in the group with intraoperative recognition (p= 0.009), while the rate of type A lesions was significantly higher in the group with postoprative recognition (p = 0.026). Intraoperatively, 83.3% of the lesions were treated by primary suture with a biliary drainage and a hepatico-jejunal anastomosis was performed immediately in one case (16.7%). Postoperatively, 85.7% of the lesions were treated by non-surgical techniques in first- line and 4 of them have undergone biliary surgery later. The total number of therapeutic procedures for each IBDI after LC was significantly higher when the diagnosis was made postoperatively (3.4 vs. 1.5, p= 0.040). Conclusion: This study has identified a patient at risk of IBDI, this one is relatively old, overweight and has an inflammatory environment. Misidentification of biliary anatomy remains the main cause. There is a clear relationship between the timing of recognition and the type of injury involved. The primary suture with adequate drainage seems to be the method of choice for intraoperative discovery, while in case of postoperative recognition, the treatment must be adapted after a multidisciplinary consensus by combining interventional radiology, endoscopy and surgery.

Composición bioquímica y distribución de la materia orgánica sedimentaria y sus efectos sobre la estructura comunitaria de la meiofauna en la plataforma continental frente a Callao.

Se estudió la composición y distribución de la materia orgánica sedimentaria en términos de Carbohidratos, Lípidos y Proteínas, así como sus repercusiones sobre la estructura comunitaria de la meiofauna metazoaria (abundancia, biomasa y diversidad a nivel de grandes grupos), además, se estima su rol en el flujo de energía del sub-sistema bentónico mediante el cálculo de la producción secundaria y respiración frente a las costas de Perú Central, Callao (12ºS). Las muestras se recolectaron en el mes de Abril del año 2010, en un gradiente batimétrico en cinco estaciones: Estación E1 (48m) y E2 (93m) correspondiente a la plataforma interna, estación E3 (117m) correspondiente a la plataforma intermedia y la estación E4 (143m) y E5 (148m) correspondiente a la plataforma externa. En cada estación se determinaron parámetros fisicoquímicos como oxígeno disuelto, salinidad y temperatura. Asimismo se determinó el contenido de pigmentos fotosintéticos (clorofila- a y feopigmentos) en la columna de sedimento.

Contribución al diseño de GNSS-SDR, un receptor GNSS de código abierto

[ANGLÈS] This project introduces GNSS-SDR, an open source Global Navigation Satellite System software-defined receiver. The lack of reconfigurability of current commercial-of-the-shelf receivers and the advent of new radionavigation signals and systems make software receivers an appealing approach to design new architectures and signal processing algorithms. With the aim of exploring the full potential of this forthcoming scenario with a plurality of new signal structures and frequency bands available for positioning, this paper describes the software architecture design and provides details about its implementation, targeting a multiband, multisystem GNSS receiver. The result is a testbed for GNSS signal processing that allows any kind of customization, including interchangeability of signal sources, signal processing algorithms, interoperability with other systems, output formats, and the offering of interfaces to all the intermediate signals, parameters and variables. The source code release under the GNU General Public License (GPL) secures practical usability, inspection, and continuous improvement by the research community, allowing the discussion based on tangible code and the analysis of results obtained with real signals. The source code is complemented by a development ecosystem, consisting of a website (http://gnss-sdr.org), as well as a revision control system, instructions for users and developers, and communication tools. The project shows in detail the design of the initial blocks of the Signal Processing Plane of the receiver: signal conditioner, the acquisition block and the receiver channel, the project also extends the functionality of the acquisition and tracking modules of the GNSS-SDR receiver to track the new Galileo E1 signals available. Each section provides a theoretical analysis, implementation details of each block and subsequent testing to confirm the calculations with both synthetically generated signals and with real signals from satellites in space.