Search

Antibiotics and antibiotic resistance determinants, natural molecules closely related to bacterial physiology and consistent with an ancient origin, are not only present in antibiotic-producing bacteria. Throughput sequencing technologies have revealed an unexpected reservoir of antibiotic resistance in the environment. These data suggest that co-evolution between antibiotic and antibiotic resistance genes has occurred since the beginning of time. This evolutionary race has probably been slow because of highly regulated processes and low antibiotic concentrations. Therefore to understand this global problem, a new variable must be introduced, that the antibiotic resistance is a natural event, inherent to life. However, the industrial production of natural and synthetic antibiotics has dramatically accelerated this race, selecting some of the many resistance genes present in nature and contributing to their diversification. One of the best models available to understand the biological impact of selection and diversification are beta-lactamases. They constitute the most widespread mechanism of resistance, at least among pathogenic bacteria, with more than 1000 enzymes identified in the literature. In the last years, there has been growing concern about the description, spread, and diversification of beta-lactamases with carbapenemase activity and AmpC-type in plasmids. Phylogenies of these enzymes help the understanding of the evolutionary forces driving their selection. Moreover, understanding the adaptive potential of beta-lactamases contribute to exploration the evolutionary antagonists trajectories through the design of more efficient synthetic molecules. In this review, we attempt to analyze the antibiotic resistance problem from intrinsic and environmental resistomes to the adaptive potential of resistance genes and the driving forces involved in their diversification, in order to provide a global perspective of the resistance problem.

Galan, J. "Extending axions searches with a spherical TPC" in Proceedings, 9th Patras Workshop on Axions, WIMPs and WISPs (AXION-WIMP 2013) / Oberlack, Uwe, Sissol, Pierre (eds.), 2013 ; AXION-WIMP 2013 : 9th Patras Workshop on Axions, WIMPs and WISPs , 2013-06-23 - 2013-06-28, Mainz 9th Patras Workshop on Axions, WIMPs and WISPs, AXION-WIMP 2013, Mainz, Germany, 24 Jun 2013 - 28 Jun 2013; Hamburg : Verlag Deutsches Elektronen-Synchrotron, DESY-PROC 59-62 (2013). doi:10.3204/DESY-PROC-2013-04/galan_javier, We present the prospects for detection of KK-axions using a large volum spherical TPC through natural decay to two gammas. The higher excited mass states of this axion model allows to reach densities which could be detectable by this method. We show the capability of this detector to detect 2-prong events coming from rest-mass axion decays and we provide efficiencies obtained under some gas mixtures and pressure conditions. The sensitivity limit of a future experiment with existing detectors geometry has been estimated for the case of zero background limit., Published by Verlag Deutsches Elektronen-Synchrotron, Hamburg

Background The present report compares prognosis in hospitalized cases with the H1N1 pandemic virus in two seasons. Methods Two series of hospitalized patients with laboratory-confirmed H1N1 pandemic influenza have been compared: 813 in the season 2009-2010 and 707 in the season 2010-2011. A detailed history of variables preceding hospital admission and during hospitalization was obtained by interview and clinical charts. A combined endpoint of death admission to intensive care was used as outcome due to the low number of deaths. Logistic regression was applied in the analysis for adverse outcome. Results Patients of the second season had different characteristics than in the first one (older, more underlying conditions, more malfunctioning organs and more symptoms). Patients with H1N1 pandemic virus when hospitalized were more frequently directly admitted to ICU during the 2010-2011 season than in the previous season (RR = 2.10; 95% confidence intervals CI, 1.55-2.85), as a consequence of a higher presence of sepsis and respiratory distress. These patients also showed during hospitalization a higher risk of ICU admission or death (RR = 3.22, 95% CI, 2.15-4.83). After adjusting for the differences in risk factors of adverse outcome, patients in the second season showed a higher risk of ICU admission and/or in-hospital death odds ratio (OR = 3.77, 95% CI, 2.30-6.18). Conclusion Hospitalized patients with H1N1 pandemic influenza during the second season were more severely affected at hospital admission and showed a worse prognosis than in previous season, independently of the differences found at hospital admission.

Background: Since influenza predisposes to bacterial pneumonia caused by Streptococcus pneumoniae, studies have suggested that pneumococcal vaccination might reduce its occurrence during pandemics. We assessed the effectiveness of pneumococcal polysaccharide vaccination alone and in combination with influenza vaccination in preventing influenza hospitalization during the 2009-2010 pandemic wave and 2010-2011 influenza epidemic. Methods: We conducted a multicenter case-control study in 36 Spanish hospitals. We selected patients aged 18 y hospitalized with confirmed influenza and two hospitalized controls per case, matched according to age, date of hospitalization and province of residence. Multivariate analysis was performed using conditional logistic regression. Subjects were considered vaccinated if they had received the pneumococcal or seasonal influenza vaccine > 14 d (or > 7 d for pandemic influenza vaccine) before the onset of symptoms (cases) or the onset of symptoms in matched cases (controls). Results: 1187 cases and 2328 controls were included. The adjusted estimate of effectiveness of pneumococcal vaccination in preventing influenza hospitalization was 41% (95% CI 8-62) in all patients and 43% (95% CI 2-78) in patients aged 65 y. The adjusted effectiveness of dual PPV23 and influenza vaccination was 81% (95% CI 65-90) in all patients and 76% (95% CI 46-90) in patients aged 65 y. The adjusted effectiveness of influenza vaccination alone was 58% (95% CI 38-72). Conclusions: In elderly people and adults with chronic illness, pneumococcal vaccination may reduce hospitalizations during the influenza season. In people vaccinated with both the influenza and pneumococcal vaccines, the benefit in hospitalizations avoided was greater than in those vaccinated only against influenza.

Background: The pneumococcal conjugate vaccine (PCV) might prevent hospitalizations in children because of the role of Streptococcus pneumoniae in the complications of influenza infection. We investigated the benefit of PCV vaccination in preventing influenza hospitalization in children

Background. In most seasons, the influenza vaccine is effective in preventing influenza, but it is not clear whether it is equally effective in preventing mild and severe cases. We designed a case-control study to compare the effectiveness of the influenza vaccine in preventing outpatient, inpatient, and severe or fatal cases of laboratory-confirmed influenza. Methods. Hospitalized patients (n = 691) with laboratory-confirmed influenza in the 2010-2011 season recruited in 29 Spanish hospitals were individually matched by age, admission/visit date, and province with an outpatient with laboratory-confirmed influenza and an outpatient control. Severe cases were considered those patients admitted to intensive care units or who died in the hospital (n = 177). We compared the influenza vaccine status of controls and outpatient cases, inpatient cases, and severe cases using conditional logistic regression adjusted for potential confounding factors. Severe and nonsevere inpatient influenza cases were compared using unconditional logistic regression. Vaccine effectiveness was (1 - odds ratio) x 100. Results. Vaccine effectiveness was 75% (adjusted odds ratio [AOR], 0.25; 95% confidence interval [CI],.16-.39) in preventing influenza outpatient cases, 60% (AOR, 0.40; 95% CI,.25-.63) in preventing influenza-associated hospitalizations, and 89% (AOR, 0.11; 95% CI,.04-.37) in preventing severe cases. In inpatients, influenza vaccination was associated with a lower risk of severe influenza (AOR, 0.42; 95% CI,.22-.80). Conclusions. Influenza vaccination prevented influenza cases and hospitalizations and was associated with a better prognosis in inpatients with influenza. The combined effect of these 2 mechanisms would explain the high effectiveness of the vaccine in preventing severe cases due to influenza.

The emergence and pandemic spread of a new strain of influenza A (H1N1) virus in 2009 resulted in a serious alarm in clinical and public health services all over the world. One distinguishing feature of this new influenza pandemic was the different profile of hospitalized patients compared to those from traditional seasonal influenza infections. Our goal was to analyze sociodemographic and clinical factors associated to hospitalization following infection by influenza A(H1N1) virus. We report the results of a Spanish nationwide study with laboratory confirmed infection by the new pandemic virus in a case-control design based on hospitalized patients. The main risk factors for hospitalization of influenza A (H1N1) 2009 were determined to be obesity (BMI >= 40, with an odds-ratio [OR] 14.27), hematological neoplasia (OR 10.71), chronic heart disease, COPD (OR 5.16) and neurological disease, among the clinical conditions, whereas low education level and some ethnic backgrounds (Gypsies and Amerinds) were the sociodemographic variables found associated to hospitalization. The presence of any clinical condition of moderate risk almost triples the risk of hospitalization (OR 2.88) and high risk conditions raise this value markedly (OR 6.43). The risk of hospitalization increased proportionally when for two (OR 2.08) or for three or more (OR 4.86) risk factors were simultaneously present

Prepared for submission to JCAP We study the feasibility of a new generation axion helioscope, the most ambitious and promising detector of solar axions to date. We show that large improvements in magnetic field volume, x-ray focusing optics and detector backgrounds are possible beyond those achieved in the CERN Axion Solar Telescope (CAST).

In July 2011, CAST finished the data-taking of its nominal programme, having scanned axion masses up to ~1.18 eV/c**2. Here we present the first results of the data taken in 2008, first year of the last data-taking campaign when $^3$He was used inside the magnet bores. No excess of signal over background has been recorded, and an upper limit has been set to the axion-to-photon coupling to 2.3*10**-10 GeV**-1 for axion masses between 0.39 and 0.64 eV. CAST remains the most sensitive axion helioscope and for the first time crosses the benchmark line of the KSVZ model at the upper end of the spectrum., Proc. of Patras Workshop on Axions, WIMPs and WISPs, 93 - 97; DESY-PROC-2011-04; ISSN 1435-8077

Extended-spectrum beta-lactamases (ESBL) constitute a key antibiotic-resistance mechanism affecting Gram-negative bacteria, and also an excellent model for studying evolution in real time. A shift in the epidemiology of ESBLs is being observed, which is characterized by the explosive diversification and increase in frequency of the CTX-M-type beta-lactamases in different settings. This provides a unique opportunity for studying a protein evolutionary radiation by the sequential acquisition of specific mutations enhancing protein efficiency and fitness concomitantly. The existence of driver antibiotic molecules favoring protein divergence has been investigated by combining evolutionary analyses and experimental site-specific mutagenesis. Phylogenetic reconstruction with all the CTX-M variants described so far provided a hypothetical evolutionary scenario showing at least three diversification events. CTX-M-3 was likely the enzyme at the origin of the diversification in the CTX-M-1 cluster, which was coincident with positive selection acting on several amino acid positions. Sixty-three CTX-M-3 derivatives containing all combinations of mutations under positively selected positions were constructed, and their phenotypic efficiency was evaluated. The CTX-M-3 diversification process can only be explained in a complex selective landscape with at least two antibiotics (cefotaxime and ceftazidime), indicating the need to invoke mixtures of selective drivers in order to understand the final evolutionary outcome. Under this hypothesis, we found congruent results between the in silico and in vitro analyses of evolutionary trajectories. Three pathways driving the diversification of CTX-M-3 towards the most complex and efficient variants were identified. Whereas the P167S pathway has limited possibilities of further diversification, the D240G route shows a robust diversification network. In the third route, drift may have played a role in the early stages of CTX-M-3 evolution. Antimicrobial agents should not be considered only as selectors for efficient mechanisms of resistance but also as diversifying agents of the evolutionary trajectories. Different trajectories were identified using a combination of phylogenetic reconstructions and directed mutagenesis analyses, indicating that such an approach might be useful to fulfill the desirable goal of predicting evolutionary trajectories in antimicrobial resistance.

Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't; Colorectal cancer is one of the most prevalent cancers in developed countries. However, the genetic factors influencing its appearance remain far from being fully characterized. Recently, a G>A functional transition mapping the 3' untranslated region of the CXCL12 gene (rs1801157) has been found to be under-represented among rectal cancer patients when compared to colon cancer patients from a Swedish series. Here we present the results from an independent analysis of CXCL12 rs1801157 in a larger CRC series of Spanish origin in order to analyse the robustness of this association within a different European population. No significant difference was observed between controls and colon or rectal cancer patients. We were also unable to find a correlation between rs1801157 and different prognostic markers such as metastasis development or disease-free survival time. The epidemiologic data involving CXCL12 rs1801157 in colorectal cancer risk are discussed. Yes

The CAST experiment at CERN is the only running solar axion telescope. The first results obtained so far with CAST-PHASE I is presented, which compete with the best astrophysically derived limits of the axion-to-photon coupling. The ongoing PHASE II of the experiment as well as the scheduled upgrades, which improve the axion discovery potential of CAST, are discussed.

"El creador de la World Wide Web (WWW), el fisico britanico Tim Berners-Lee, gano hoy la primera edicion del Millennium Technology Prize, un galardon internacional creado por una fundacion finlandesa y dotado con un millon de euros" (1/2 page)