449,983 research outputs found

    Sepsis at ICU admission does not decrease 30-day survival in very old patients: a post-hoc analysis of the VIP1 multinational cohort study

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    Background: The number of intensive care patients aged ≥ 80 years (Very old Intensive Care Patients; VIPs) is growing. VIPs have high mortality and morbidity and the benefits of ICU admission are frequently questioned. Sepsis incidence has risen in recent years and identification of outcomes is of considerable public importance. We aimed to determine whether VIPs admitted for sepsis had different outcomes than those admitted for other acute reasons and identify potential prognostic factors for 30-day survival. Results: This prospective study included VIPs with Sequential Organ Failure Assessment (SOFA) scores ≥ 2 acutely admitted to 307 ICUs in 21 European countries. Of 3869 acutely admitted VIPs, 493 (12.7%) [53.8% male, median age 83 (81–86) years] were admitted for sepsis. Sepsis was defined according to clinical criteria; suspected or demonstrated focus of infection and SOFA score ≥ 2 points. Compared to VIPs admitted for other acute reasons, VIPs admitted for sepsis were younger, had a higher SOFA score (9 vs. 7, p < 0.0001), required more vasoactive drugs [82.2% vs. 55.1%, p < 0.0001] and renal replacement therapies [17.4% vs. 9.9%; p < 0.0001], and had more life-sustaining treatment limitations [37.3% vs. 32.1%; p = 0.02]. Frailty was similar in both groups. Unadjusted 30-day survival was not significantly different between the two groups. After adjustment for age, gender, frailty, and SOFA score, sepsis had no impact on 30-day survival [HR 0.99 (95% CI 0.86–1.15), p = 0.917]. Inverse-probability weight (IPW)-adjusted survival curves for the first 30 days after ICU admission were similar for acute septic and non-septic patients [HR: 1.00 (95% CI 0.87–1.17), p = 0.95]. A matched-pair analysis in which patients with sepsis were matched with two control patients of the same gender with the same age, SOFA score, and level of frailty was also performed. A Cox proportional hazard regression model stratified on the matched pairs showed that 30-day survival was similar in both groups [57.2% (95% CI 52.7–60.7) vs. 57.1% (95% CI 53.7–60.1), p = 0.85]. Conclusions: After adjusting for organ dysfunction, sepsis at admission was not independently associated with decreased 30-day survival in this multinational study of 3869 VIPs. Age, frailty, and SOFA score were independently associated with survival

    Possible inhibition of Arabidopsis VIP1-mediated mechanosensory signaling by streptomycin

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    VIP1 (VIRE2-INTERACTING PROTEIN 1) and its close homologues are Arabidopsis thaliana bZIP proteins regulating stress responses and root tropisms. They are present in the cytoplasm under steady conditions, but transiently accumulate in the nucleus when cells are exposed to mechanical stress such as hypo-osmotic stress and touch. This pattern of changes in subcellular localization is unique to VIP1 and its close homologues, and can be useful to further characterize mechanical stress signaling in plants. A recent study showed that calcium signaling regulates this pattern of subcellular localization. Here, we show that a possible calcium channel inhibitor, streptomycin, also inhibits the nuclear accumulation of VIP1. Candidates for the specific regulators of the mechanosensitive calcium signaling are further discussed

    A Chemical Genetic Strategy to Study Vip1 in Inositol Pyrophosphate Signaling

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    The water-soluble and highly phosphorylated inositol pyrophosphates (PP-IPs) are a conserved class of signaling molecules. Genetic studies in yeast have implicated the PPIPs in a variety of roles, including nutrient sensing and response to environmental stress, but have largely proven ineffective in decoding their mechanisms of action. This thesis focuses on developing a chemical genetic approach for an in-depth analysis of the signaling roles of Vip1, an ATP-grasp kinase, and its corresponding PP-IP products in Saccharomyces cerevisiae. The technique relies on strategically introducing mutations into the kinase active site and developing orthogonal ATP analogs. I report the successful identification and engineering of analog sensitive alleles of Vip1 (Vip1-AS) that maintain functionality both biochemically and in yeast. Furthermore, I use a structure-guided approach to develop a small class of biorthogonal ATP-competitive pyridopyrimidines, and demonstrate their potency against and selectivity for Vip1-AS in vitro. Though inhibition studies in yeast are thus far incomplete, preliminary results provide promising evidence for the successful creation of an appropriate chemical genetic system for Vip1. Once verified and optimized, the system can be not only applied to investigate Vip1¿s role in transcriptional and metabolic regulation, but also extended to examine homologues in higher-order eukaryotes and structurally similar enzymes within the ATPgrasp superfamily

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Relationship between the Clinical Frailty Scale and short-term mortality in patients ≥ 80 years old acutely admitted to the ICU: a prospective cohort study

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    Background: The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context. Methods: We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient’s age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score. Results: The median age in the sample of 7487 consecutive patients was 84 years (IQR 81–87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p < 0.001). The relationship between the CFS score and mortality was nonlinear (p < 0.01). Conclusion: Knowledge about a patient’s frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided. Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2

    Identificação e caracterização de genes cry3, vip1, vip2 E vip1/vip2 em isolados de Bacillus thuringiensis E toxicidade em larvas de Anthonomus grandis (Boheman, 1883) (Coleoptera: curculionidae)

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    O controle biológico utilizando microrganismos vem sendo estudado como uma alternativa ao uso de agroquímicos. Estes pesticidas poluem o ambiente, além de serem tóxicos a diversas espécies vegetais e animais. Diante disso, a bactéria Bacillus thuringiensis é um importante entomopatógeno que vem sendo utilizado na agricultura pelo fato de secretar proteínas que são tóxicas a insetos pertencentes a diversas ordens. Dentre os diversos genes de B. thuringiensis que codificam proteínas tóxicas, as classes vip1, vip2 e cry3 destacam-se como alternativa para o controle de insetos-praga da ordem Coleoptera. O presente trabalho objetivou a identificação e caracterização molecular, por meio da técnica de PCR-RFLP, dos genes cry3, vip1, vip2 e vip1/vip2 em uma coleção de B. thuringiensis, quanto a possíveis polimorfismos existentes, procurando relacioná-los à toxicidade em larvas de Anthonomus grandis. Da análise de 1078 isolados de B. thuringiensis, foram encontrados 151 isolados positivos para os genes em estudo e 14 perfis polimórficos, indicando a presença de subclasses destes genes. Os resultados obtidos nos ensaios de toxicidade indicam que os polimorfismos gênicos podem apresentar interferência na toxicidade das proteínas, sendo que a toxina Cry3 apresentou uma maior efetividade na mortalidade em larvas de A. grandis. Os resultados também evidenciaram que a PCR-RFLP mostrou-se apropriada para a detecção da variabilidade genética em B. thuringiensis, permitindo a identificação de haplótiposBiological control using microorganisms is being studied as an alternative to the use of agrochemicals. These pesticides pollute the environment, being toxic to many species of plants and animals. For these reasons, the bacterium Bacillus thuringiensis is an important entomopathogen that has been used in agriculture, once it produces proteins that are toxic to many target insect orders. Among several genes from B. thuringiensis that encode toxic proteins there are vip1, vip2 and cry3 classes that stand as an alternative for controlling insect pests belonging the Coleoptera order. The objective of this work was to identify and characterize molecularly, through PCR-RFLP, the genes cry3, vip1, vip2 and vip1/vip2 in a collection of B. thuringiensis, for possible polymorphisms exist, trying to relate them to the toxicity in Anthonomus grandis larvae. Analysis of 1078 isolates of B. thuringiensis, were found 151 positive isolates for the genes under study and 10 polymorphic profiles, which indicate the presence of subclasses of the genes. These results obtained in tests toxicity indicate that polymorphisms gene may have interference with the toxicity of the protein, and the toxin Cry3 showed a greater effectiveness in mortality in A. grandis larvae. These results also showed that the PCR-RFLP proved to be suitable for the detection of genetic variability in B. thuringiensis, allowing the identification of haplotypesCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

    Identificação e caracterização de genes cry3, vip1, vip2 E vip1/vip2 em isolados de Bacillus thuringiensis E toxicidade em larvas de Anthonomus grandis (Boheman, 1883) (Coleoptera: curculionidae)

    No full text
    O controle biológico utilizando microrganismos vem sendo estudado como uma alternativa ao uso de agroquímicos. Estes pesticidas poluem o ambiente, além de serem tóxicos a diversas espécies vegetais e animais. Diante disso, a bactéria Bacillus thuringiensis é um importante entomopatógeno que vem sendo utilizado na agricultura pelo fato de secretar proteínas que são tóxicas a insetos pertencentes a diversas ordens. Dentre os diversos genes de B. thuringiensis que codificam proteínas tóxicas, as classes vip1, vip2 e cry3 destacam-se como alternativa para o controle de insetos-praga da ordem Coleoptera. O presente trabalho objetivou a identificação e caracterização molecular, por meio da técnica de PCR-RFLP, dos genes cry3, vip1, vip2 e vip1/vip2 em uma coleção de B. thuringiensis, quanto a possíveis polimorfismos existentes, procurando relacioná-los à toxicidade em larvas de Anthonomus grandis. Da análise de 1078 isolados de B. thuringiensis, foram encontrados 151 isolados positivos para os genes em estudo e 14 perfis polimórficos, indicando a presença de subclasses destes genes. Os resultados obtidos nos ensaios de toxicidade indicam que os polimorfismos gênicos podem apresentar interferência na toxicidade das proteínas, sendo que a toxina Cry3 apresentou uma maior efetividade na mortalidade em larvas de A. grandis. Os resultados também evidenciaram que a PCR-RFLP mostrou-se apropriada para a detecção da variabilidade genética em B. thuringiensis, permitindo a identificação de haplótiposBiological control using microorganisms is being studied as an alternative to the use of agrochemicals. These pesticides pollute the environment, being toxic to many species of plants and animals. For these reasons, the bacterium Bacillus thuringiensis is an important entomopathogen that has been used in agriculture, once it produces proteins that are toxic to many target insect orders. Among several genes from B. thuringiensis that encode toxic proteins there are vip1, vip2 and cry3 classes that stand as an alternative for controlling insect pests belonging the Coleoptera order. The objective of this work was to identify and characterize molecularly, through PCR-RFLP, the genes cry3, vip1, vip2 and vip1/vip2 in a collection of B. thuringiensis, for possible polymorphisms exist, trying to relate them to the toxicity in Anthonomus grandis larvae. Analysis of 1078 isolates of B. thuringiensis, were found 151 positive isolates for the genes under study and 10 polymorphic profiles, which indicate the presence of subclasses of the genes. These results obtained in tests toxicity indicate that polymorphisms gene may have interference with the toxicity of the protein, and the toxin Cry3 showed a greater effectiveness in mortality in A. grandis larvae. These results also showed that the PCR-RFLP proved to be suitable for the detection of genetic variability in B. thuringiensis, allowing the identification of haplotypesCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

    Identificação e caracterização de genes cry3, vip1, vip2 E vip1/vip2 em isolados de Bacillus thuringiensis E toxicidade em larvas de Anthonomus grandis (Boheman, 1883) (Coleoptera: curculionidae)

    No full text
    O controle biológico utilizando microrganismos vem sendo estudado como uma alternativa ao uso de agroquímicos. Estes pesticidas poluem o ambiente, além de serem tóxicos a diversas espécies vegetais e animais. Diante disso, a bactéria Bacillus thuringiensis é um importante entomopatógeno que vem sendo utilizado na agricultura pelo fato de secretar proteínas que são tóxicas a insetos pertencentes a diversas ordens. Dentre os diversos genes de B. thuringiensis que codificam proteínas tóxicas, as classes vip1, vip2 e cry3 destacam-se como alternativa para o controle de insetos-praga da ordem Coleoptera. O presente trabalho objetivou a identificação e caracterização molecular, por meio da técnica de PCR-RFLP, dos genes cry3, vip1, vip2 e vip1/vip2 em uma coleção de B. thuringiensis, quanto a possíveis polimorfismos existentes, procurando relacioná-los à toxicidade em larvas de Anthonomus grandis. Da análise de 1078 isolados de B. thuringiensis, foram encontrados 151 isolados positivos para os genes em estudo e 14 perfis polimórficos, indicando a presença de subclasses destes genes. Os resultados obtidos nos ensaios de toxicidade indicam que os polimorfismos gênicos podem apresentar interferência na toxicidade das proteínas, sendo que a toxina Cry3 apresentou uma maior efetividade na mortalidade em larvas de A. grandis. Os resultados também evidenciaram que a PCR-RFLP mostrou-se apropriada para a detecção da variabilidade genética em B. thuringiensis, permitindo a identificação de haplótiposBiological control using microorganisms is being studied as an alternative to the use of agrochemicals. These pesticides pollute the environment, being toxic to many species of plants and animals. For these reasons, the bacterium Bacillus thuringiensis is an important entomopathogen that has been used in agriculture, once it produces proteins that are toxic to many target insect orders. Among several genes from B. thuringiensis that encode toxic proteins there are vip1, vip2 and cry3 classes that stand as an alternative for controlling insect pests belonging the Coleoptera order. The objective of this work was to identify and characterize molecularly, through PCR-RFLP, the genes cry3, vip1, vip2 and vip1/vip2 in a collection of B. thuringiensis, for possible polymorphisms exist, trying to relate them to the toxicity in Anthonomus grandis larvae. Analysis of 1078 isolates of B. thuringiensis, were found 151 positive isolates for the genes under study and 10 polymorphic profiles, which indicate the presence of subclasses of the genes. These results obtained in tests toxicity indicate that polymorphisms gene may have interference with the toxicity of the protein, and the toxin Cry3 showed a greater effectiveness in mortality in A. grandis larvae. These results also showed that the PCR-RFLP proved to be suitable for the detection of genetic variability in B. thuringiensis, allowing the identification of haplotypesCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

    The UN-SUSTAINABLE Match in HCV Recipients. Evidences from the Italian D-MELD Study on Balancing Donor-Recipient Risk Factors

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    The UN-SUSTAINABLE Match in HCV Recipients. Evidences from the Italian D-MELD Study on Balancing Donor-Recipient Risk Factor

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods
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