9 research outputs found

    Pyrosequencing-based analysis reveals a novel capsular gene cluster in a KPC-producing Klebsiella pneumoniae clinical isolate identified in Brazil

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    Background: An important virulence factor of Klebsiella pneumoniae is the production of capsular polysaccharide (CPS), a thick mucus layer that allows for evasion of the host's defense and creates a barrier against antibacterial peptides. CPS production is driven mostly by the expression of genes located in a locus called cps, and the resulting structure is used to distinguish between different serotypes (K types). in this study, we report the unique genetic organization of the cps cluster from K. pneumoniae Kp13, a clinical isolate recovered during a large outbreak of nosocomial infections that occurred in a Brazilian teaching hospital.Results: A pyrosequencing-based approach showed that the cps region of Kp13 (cps(Kp13)) is 26.4 kbp in length and contains genes common, although not universal, to other strains, such as the rm/BADC operon that codes for L-rhamnose synthesis. cpsKp13 also presents some unique features, like the inversion of the wzy gene and a unique repertoire of glycosyltransferases. in silico comparison of cps(Kp13) RFLP pattern with 102 previously published cps PCR-RFLP patterns showed that cpsKp13 is distinct from the C patterns of all other K serotypes. Furthermore, in vitro serotyping showed only a weak reaction with capsular types K9 and K34. We confirm that K9 cps shares common genes with cps(Kp13) such as the rm/BADC operon, but lacks features like uge and Kp13-specific glycosyltransferases, while K34 capsules contain three of the five sugars that potentially form the Kp13 CPS.Conclusions: We report the first description of a cps cluster from a Brazilian clinical isolate of a KPC-producing K. pneumoniae. the gathered data including K-serotyping support that Kp13's K-antigen belongs to a novel capsular serotype. the CPS of Kp13 probably includes L-rhamnose and D-galacturonate in its structure, among other residues. Because genes involved in L-rhamnose biosynthesis are absent in humans, this pathway may represent potential targets for the development of antimicrobial agents. Studying the capsular serotypes of clinical isolates is of great importance for further development of vaccines and/or novel therapeutic agents. the distribution of K-types among multidrug-resistant isolates is unknown, but our findings may encourage scientists to perform K-antigen typing of KPC-producing strains worldwide.LNCC, Rio de Janeiro, BrazilUniv Fed Rio de Janeiro, Inst Microbiol Paulo de Goes, Rio de Janeiro, BrazilUniv Estadual Londrina, Dept Patol Clin Anal Clin & Toxicol, Londrina, BrazilUniversidade Federal de São Paulo, Lab ALERTA, Div Doencas Infecciosas, São Paulo, BrazilUniversidade Federal de São Paulo, Lab ALERTA, Div Doencas Infecciosas, São Paulo, BrazilWeb of Scienc

    The polymyxin B-induced transcriptomic response of a clinical, multidrug-resistant Klebsiella pneumoniae involves multiple regulatory elements and intracellular targets

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    Background: The emergence of multidrug-resistant Klebsiella pneumoniae is a major public health concern. Many K. pneumoniae infections can only be treated when resorting to last-line drugs such as polymyxin B (PB). However, resistance to this antibiotic is also observed, although insufficient information is described on its mode of action as well as the mechanisms used by resistant bacteria to evade its effects. We aimed to study PB resistance and the influence of abiotic stresses in a clinical K. pneumoniae strain using whole transcriptome profiling. Results: We sequenced 12 cDNA libraries of K. pneumoniae Kp13 bacteria, from two biological replicates of the original strain Kp13 (Kp13) and five derivative strains: induced high-level PB resistance in acidic pH (Kp13(pH)), magnesium deprivation (Kp13(Mg)), high concentrations of calcium (Kp13(Ca)) and iron (Kp13(Fe)), and a control condition with PB (Kp13(PolB)). Our results show the involvement of multiple regulatory loci that differentially respond to each condition as well as a shared gene expression response elicited by PB treatment, and indicate the participation of two-regulatory components such as ArcA-ArcB, which could be involved in re-routing the K. pneumoniae metabolism following PB treatment. Modules of co-expressed genes could be determined, which correlated to growth in acid stress and PB exposure. We hypothesize that polymyxin B induces metabolic shifts in K. pneumoniae that could relate to surviving against the action of this antibiotic. Conclusions: We obtained whole transcriptome data for K. pneumoniae under different environmental conditions and PB treatment. Our results supports the notion that the K. pneumoniae response to PB exposure goes beyond damaged membrane reconstruction and involves recruitment of multiple gene modules and intracellular targets.Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Lab Nacl Comp Cient, Petropolis, RJ, BrazilFiocruz MS, Ctr Pesquisas Goncalo Moniz, Salvador, BA, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Internal Med, Lab Alerta,Div Infect Dis, Sao Paulo, SP, BrazilUniv Catolica Cordoba, Fac Ingn, CONICET, Cordoba, ArgentinaUniv Fed Sao Paulo, Escola Paulista Med, Dept Internal Med, Lab Alerta,Div Infect Dis, Sao Paulo, SP, BrazilFAPERJ: E-26/110.315/2014FAPESP: 2010/12891-9CAPES: 23038.010041/2013-13Web of Scienc

    A perspetiva dos professores de educação especial sobre a importância da expressão dramática como técnica psicopedagógica no desenvolvimento da comunicação da criança com perturbação de Asperger

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    Os princípios pelos quais a escola inclusiva se rege defendem que os alunos não devem apenas estar juntos, mas acima de tudo, devem aprender juntos, de forma a perceberem que a escola é de todos e para todos, ainda que dentro das suas diferenças. Terá o professor capacidades, conhecimentos e estratégias suficientes para abraçar este desafio? Numa tentativa de aprofundarmos o nosso conhecimento acerca da Perturbação de Asperger propomo-nos a desenvolver um trabalho que defina a doença, dentro do já então conhecido, e evidencie tanto as “fragilidades” como as “capacidades” dos portadores, carinhosamente apelidados de “Aspies”. Trata-se de uma tentativa de reunir os conhecimentos necessários para começar a entender a essência dos Asperger. Porque é que na opinião do psicólogo clínico Tony Attwood, especialista mundial nesta Perturbação, precisamos de pessoas com Asperger, sugerindo que estes indivíduos possam ser, de alguma forma, especiais e capazes de grandes feitos. Neste sentido, surge este estudo para tentar perceber a perspetiva dos professores de Educação Especial sobre a importância da Expressão Dramática como técnica psicopedagógica no desenvolvimento da comunicação da criança com Perturbação de Asperger. Pretendemos perceber a influência que a utilização desta técnica pode ter no desenvolvimento comunicacional da criança com Perturbação de Asperger, pois talvez seja relevante sugerir a elaboração de um programa de treino de competências comunicacionais que utilize a Expressão Dramática. A Expressão Dramática vai além do seu papel de ferramenta lúdica e de distração, daí a importância de se conhecer as vantagens da sua utilização nesta área e tentar perceber se pode contribuir ou não para o sucesso de uma criança com esta problemática

    Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

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    Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

    Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

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    Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019

    A whole genome bioinformatic approach to determine potential latent phase specific targets in Mycobacterium tuberculosis

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    Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-07-07T16:18:51Z No. of bitstreams: 1 Defelipe LA A whole genome.pdf: 2551463 bytes, checksum: 9b2a7bb2e8e75abeb1f6bb886d4e079e (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-07-07T16:30:32Z (GMT) No. of bitstreams: 1 Defelipe LA A whole genome.pdf: 2551463 bytes, checksum: 9b2a7bb2e8e75abeb1f6bb886d4e079e (MD5)Made available in DSpace on 2016-07-07T16:30:32Z (GMT). No. of bitstreams: 1 Defelipe LA A whole genome.pdf: 2551463 bytes, checksum: 9b2a7bb2e8e75abeb1f6bb886d4e079e (MD5) Previous issue date: 2016Made available in DSpace on 2016-07-08T18:41:58Z (GMT). No. of bitstreams: 3 Defelipe LA A whole genome.pdf.txt: 72857 bytes, checksum: 6f5d198733e0f50e22fc5d78d02cc9aa (MD5) Defelipe LA A whole genome.pdf: 2551463 bytes, checksum: 9b2a7bb2e8e75abeb1f6bb886d4e079e (MD5) license.txt: 2991 bytes, checksum: 5a560609d32a3863062d77ff32785d58 (MD5) Previous issue date: 2016Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biologica. Buenos Aires, ArgentinaInstituto de C alculo. Facultad de Ciencias Exactas y Naturales. Plataforma de Bioinformatica Argentina. Buenos Aires, ArgentinaFundação Gonçalo Moniz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Laboratório Nacional de Computação Científica. Petrópolis, RJ, BrasilLaboratório Nacional de Computação Científica. Petrópolis, RJ, BrasilInstituto de Calculo. Facultad de Ciencias Exactas y Naturales. Plataforma de Bioinformatica Argentina. Buenos Aires, ArgentinaUniversidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biologica. Buenos Aires, ArgentinaUniversidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biologica. Buenos Aires, ArgentinaUniversidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biologica. Buenos Aires, ArgentinaUniversidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biologica. Buenos Aires, ArgentinaCurrent Tuberculosis treatment is long and expensive, faces the increasing burden of MDR/XDR strains and lack of effective treatment against latent form, resulting in an urgent need of new anti-TB drugs. Key to TB biology is its capacity to fight the host's RNOS mediated attack. RNOS are known to display a concentration dependent mycobactericidal activity, which leads to the following hypothesis ”if we know which proteins are targeted by RNOS and kill TB, we we might be able to inhibit them with drugs resulting in a synergistic bactericidal effect”. Based on this idea, we performed an Mtb metabolic network whole proteome analysis of potential RNOS sensitive and relevant targets which includes target druggability and essentiality criteria. Our results, available at http://tuberq.proteinq.com.ar yield new potential TB targets, like I3PS, while also providing and updated view of previous proposals becoming an important tool for researchers looking for new ways of killing T

    Study of pomological traits and physico-chemical quality of pomegranate (Punica granatum L.) genotypes grown in Italy

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    Pomegranate is considered a functional food but several local accessions and cultivars are widespread in different countries. The characterization of local germoplasm allows to identify genotypes that possess the highest nutraceutical value compared to standard cultivars (cvs.) and that are well-adapted to local climatic conditions and could be used in the breeding programs. The aim of this study was the characterization of pomological and physico-chemical traits as well as antioxidant system in local pomegranate accessions (‘Mondrone Dolce’, ‘San Pietro’, ‘Granato’ and ‘Roce’), comparing to an Italian (‘Dente di Cavallo’) and international cvs. (‘Wonderful’). A high variability of the pomological traits resulted among the cultivars. ‘Wonderful’ showed the highest value of anthocyanins (554.99 ± 0.05 mg C3gE L−1), total phenols (1494.00 ± 116.20 mg GAE L−1) and antioxidant activity (EC50values 21.21 ± 0.05 µL mL−1), whereas ‘Granato’ had the highest values among local accessions. Furthermore, the antioxidant enzymes activities varied with genotypes. Principal component analysis revealed great differences in all investigated parameters among pomegranate genotypes. ‘Mondrone Dolce’, ‘San Pietro’ and ‘Dente di Cavallo’ showed similar pomological and nutraceutical traits compared to ‘Granato’ and ‘Roce’. Conversely, ‘Wonderful’, due to its peculiar traits, revealed significant differences with respect to other genotypes

    Five insights from the Global Burden of Disease Study 2019

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