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Evolutionary Dynamics of Influenza Type B in the Presence of Vaccination: An Ecological StudyFiedler, Lindsey J. 24 June 2019 (has links)
Understanding the evolutionary dynamics of influenza type B in human hosts is a public health concern as we strive to minimize the disease burden in seasonal epidemics. Vaccination is considered the best defense against contracting influenza, and everyone over the age of 6 months is advised to get vaccinated before each season. The effect that vaccine-acquired immunity has on the evolution of influenza B remains unclear. In the U.S., vaccine-uptake is irregular across the states, and the differing coverages present an opportunity to study how vaccination influences viral evolution. This thesis analyzes the evolutionary patterns of influenza B in the presence of vaccine-induced selective pressure. Using an ecological study design, estimates on statewide vaccination coverages from the Centers for Disease Control and Prevention were related to influenza B sequence data. The phylogenies and the frequencies of single nucleotide polymorphisms for high and low coverage states across three influenza seasons were compared to evaluate if there was evidence of vaccination influencing evolution. Overall, the results show that vaccination does not significantly impact the evolutionary dynamics of influenza B with both high and low coverage states showing interspersed phylogenetic trees and similar antigenic diversities.
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Padrões espaciais e temporais na predação do coral construtor Montastrea Cavernosa e de algas calcarias incrustantes por budiões (Pisces: Labridae: Scarinae e Sparisomatinae) no Banco dos Abrolhos, BA / Spatial and temporal patterns of predation on coral Montastrea Cavernosa builder and encrusting coralline algae by parrotfish (Pisces: Labridae: Scarinae and Sparisomatinae) in the Abrolhos Bank, BAFerreira, Camilo Moitinho 28 February 2012 (has links)
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Previous issue date: 2012-02-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The benefits of herbivory by parrotfishes in reef systems have been relatively well studied. However, in recent years some studies have put these benefits in check. Although they feed preferentially on algae may also consume the parrotfish and coral encrusting coralline algae (ACIs), thus compromising the growth and reproduction of corals and facilitating the colonization of open spaces by non-builders. The study presented here aims to describe the spatial and temporal dynamics in density and biomass of parrotfish in the Abrolhos Bank and its relation to predation of coral Montastrea carvenosa and ACIs. The parrotfish and the two functional groups (scrapers and excavators) showed distinct spatial patterns. There was no temporal variation in the density and biomass of parrotfish. This same pattern was observed for coverage area and relative preyed on M. cavernosa and ACIs. Encrusting coralline algae covered by epilithic algae (ACICS) were the only organisms that are influenced by density and biomass of scrapers excavators. It registered a strong positive influence of biomass Sc. trispinosus in coverage without encrusting coralline algae coverage epilithic algae (ACISs) and M. cavernosa. The absence of temporal variation in the area preyed on M. cavernosa may be due to (1) low intensity of predation to detect temporal patterns clear, (2) low density and biomass of the top predator of coral, Sp.amplum, and (3) low preference for this coral parrotfish. In addition, predation on ACICS is probably beneficial for the reef system, since this substrate is competition areas between epilithic IACs and algae. Our results indicate that the parrotfish play beneficial effect on corals, stressing the need for conservation of this threatened group of overfishing. / Os benefícios proporcionados pela herbivoria dos budiões em sistemas recifais têm sido relativamente bem estudados. Entretanto, nos últimos anos, alguns estudos colocaram tais benefícios em cheque. Apesar de se alimentarem preferencialmente de algas os budiões podem também consumir corais e algas calcárias incrustantes (ACIs), comprometendo assim o crescimento e reprodução dos corais e facilitando a colonização dos espaços abertos por organismos não construtores. O estudo apresentado aqui visa descrever a dinâmica espacial e temporal na densidade e biomassa de budiões no Banco dos Abrolhos e sua relação com a predação do coral Montastrea carvenosa e ACIs. Os budiões e os dois grupos funcionais (raspadores e escavadores) apresentaram padrões espaciais distintos. Não houve variação temporal na densidade e biomassa de budiões. Esse mesmo padrão foi observado para cobertura relativa e área relativa predada de M. cavernosa e ACIs. Algas calcárias incrustantes recobertas por algas epilíticas (ACICs) foram os únicos organismos que sofreram influência da densidade de raspadores e biomassa de escavadores. Foi registrada uma forte influência positiva da biomassa de Sc. trispinosus na cobertura de algas calcárias incrustantes sem cobertura de algas epilíticas (ACISs) e de M. cavernosa. A ausência de variação temporal na área relativa predada de M. cavernosa pode ter ocorrido por (1) baixa intensidade de predação para detecção de padrões temporais nítidos; (2) baixa densidade e biomassa do principal predador desse coral, Sp.amplum; e (3) baixa preferência dos budiões por este coral. Além disso, a predação em ACICs provavelmente é benéfica para o sistema recifal, pois este substrato representa áreas de competição entre ACIs e algas epilíticas. Os resultados aqui obtidos indicam que os budiões desempenham efeito benéfico sobre os corais, salientando a necessidade de conservação deste grupo ameaçado de sobrepesca.
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Synthesis and Characterization of BN-tryptophan and its Incorporation into Proteins & the Cation-π Binding Ability of BN-indole:Boknevitz, Katherine Lynn Michelle January 2020 (has links)
Thesis advisor: Shih-Yuan Liu / Described herein are two projects on the application and effects of BN/CC isosterism on indole-containing compounds. In the first chapter, the synthetic route to an unnatural boron and nitrogen-containing analogue of tryptophan (BN-tryptophan) via late-stage functionalization of BN-indole is disclosed and its spectroscopic properties are reported with respect to the natural amino acid, tryptophan. The incorporation of BN-tryptophan into proteins expressed in E. coli using selective pressure incorporation, a residue specific method of unnatural amino acid incorporation, is then reported and its reactivity and fluorescence in the proteins characterized. In the second chapter, the synthesis of a BN-indole-containing aromatic scaffold is reported and the cation-π binding ability characterized by nuclear magnetic resonance (NMR) monitored titrations is disclosed. The resulting chemical shifts were analyzed using a non-linear curve fitting procedure and the extracted association constants (Ka’s) compared with the natural indole scaffold. Computations were also performed to support the titration results. / Thesis (PhD) — Boston College, 2020. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.
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Laboratory Detection and Gene Cassette Stability of the Novel Extended-Spectrum Beta-Lactamase, GES-2 from Pseudomonas aeruginosaWeldhagen, Gerhard Frederick 04 November 2005 (has links)
Extended-spectrum beta-lactamases (ESBLs) in Pseudomonas aeruginosa tend to be geographically scattered, such as GES-2, which partially compromises the efficacy of imipenem. The G170N mutation, ascribed to a CC to AA base pair substitution on positions 493-494 of the blaGES-2 coding region, distinguishes this ESBL from blaGES-1 and the blaIBC-type genes, making it an ideal target for developing a novel sequence-specific, peptide nucleic acid (PNA)-based, multiplex-PCR detection method. Utilizing two primer pairs in conjunction with a PNA probe, this novel method delivered accurate identification of blaGES-2 compared to standard PCR and gene sequencing techniques, when tested against one hundred (n = 100) P. aeruginosa clinical isolates as well as previously published, well-described control strains. This method has the potential to be used in large-scale, cost-effective screening programmes for specific or geographically restricted ESBLs. To date, in addition to being only described in South Africa, GES-2 is notoriously difficult to identify in P. aeruginosa, using standard methodology. A real-time PCR method using the LightCycler™ was compared to a two-step nested-PCR assay for the detection of blaGES and blaIBC genes from one hundred P. aeruginosa clinical isolates collected over a four-year period from two teaching hospitals in Pretoria, South Africa. Real-time PCR amplification was monitored through hybridisation of fluorescently labelled probes followed by melting curve analysis to detect the relevant G170N mutation occurring in the omega loop region of blaGES-2. Nested-PCR products were subjected to automated DNA sequencing and compared to melting point (Tm) analyses results obtained from the LightCycler assay. Real time and nested-PCR assays detected a blaIBC gene product from 83 and 88 clinical isolates respectively, with the LightCycler thus exhibiting a sensitivity of 94.3% compared to the nested-PCR assay. Comparison of Tm and gene sequencing data however revealed 100% specificity for sequence specific detection of blaGES-2 with the LightCycler. One clinical isolate was found to harbour a blaGES-1 gene, making this the first report of this specific ESBL from South Africa. Selective antibiotic pressure has recently been implicated as a possible driving force behind point mutations observed in blaGES–type genes. This part of the study subjected two well-characterized clinical isolates with class 1 integron-borne blaGES-type genes to five days incubation in the presence of sub-inhibitory concentrations of 15 different antibiotics, including beta-lactams, aminoglycosides and quinolones. Restriction enzyme analysis and DNA sequencing of blaGES-1, blaGES-2 and their immediate upstream genetic environments failed to demonstrate any changes compared to non-exposed controls. Short-term exposure to a sub-inhibitory level of a single antimicrobial agent is thus unlikely to select significant mutations in these beta-lactamase genes or their regulatory mechanisms. / Thesis (PhD (Medical Microbiology))--University of Pretoria, 2004. / Medical Microbiology / unrestricted
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Controle da pressão seletiva em algoritmo genético aplicado a otimização de demanda em infra-estrutura aeronáutica. / Selective pressure control in genetic algorithms applied to demand optimization in aeronautical infraestructure.Camargo, Gilberto de Menezes 18 August 2006 (has links)
A busca por entender e copiar o majestoso mundo que nos cerca fez do homem um curioso por natureza. Santos Dumont realizou a proeza de alcançar um dos sonhos mais antigos do homem, voar. Charles Darwin escreveu a Teoria da Evolução como um paradigma para a nossa existência, inspirando John Holland a desenvolver os Algoritmos Genéticos. Atualmente, com o grande crescimento da demanda no transporte aéreo, o homem volta seus esforços na busca por soluções que garantam a segurança da sociedade. Recentemente o pesquisador Naufal reuniu todos esses conceitos e desenvolveu um Modelo de Otimização de Demanda para o setor aeronáutico. Tal modelo visa amenizar a carga de trabalho dos controladores de tráfego aéreo na busca por aumentar a qualidade do serviço prestado por esse profissional, garantindo dessa forma níveis aceitáveis de segurança. Embora o modelo tenha se mostrado eficiente, ele apresentou uma deficiência quanto aos tempos despendidos para alcançar bons resultados. Na tentativa de otimizar os tempos do modelo atual, este trabalho de pesquisa adicionou o conceito de pressão seletiva, que representa a influência do meio ambiente. A representação da influência que o meio ambiente tem dentro da teoria da evolução de Darwin pode gerar uma implementação mais realista dos algoritmos genéticos. Este trabalho propõe a aplicação dos métodos de controle da pressão seletiva como alternativa de diminuir os tempos despendidos pelo modelo de otimização de demanda na busca por aumentar a segurança do setor aeroviário. / The search for understanding and copying the magnificent world that surrounds us has made man curious by nature. Santos Dumont achieved one of man?s most ancient dreams, to fly. Charles Darwin wrote the Theory of Evolution as a paradigm of our existence, inspiring John Holland to develop genetic algorithms. Presently, because of the growth of demand in air transportation, men concentrate their efforts in the search for solutions that can guarantee the safety of our society. Recently, researcher Naufal has gathered all these concepts and developed a Demand Optimization Model for the aeronautical sector. This model aims to ease the workload of air traffic controllers, in a search for increasing the quality of this service and guaranteeing acceptable levels of safety. Although his model has proved to be efficient, it has presented a weak point when it comes to time spent to reach good results. In an attempt to optimize time in the existing model, this research added the concept of selective pressure, which represents the influence of the environment. The representation of the influence that the environment has inside Darwin?s Theory of Evolution can generate a more realistic implementation of genetic algorithms. This work proposes an application of selective pressure control methods as an alternative to diminish time spent by the Demand Optimization Model in a search for increasing safety for the aeronautical sector.
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Controle da pressão seletiva em algoritmo genético aplicado a otimização de demanda em infra-estrutura aeronáutica. / Selective pressure control in genetic algorithms applied to demand optimization in aeronautical infraestructure.Gilberto de Menezes Camargo 18 August 2006 (has links)
A busca por entender e copiar o majestoso mundo que nos cerca fez do homem um curioso por natureza. Santos Dumont realizou a proeza de alcançar um dos sonhos mais antigos do homem, voar. Charles Darwin escreveu a Teoria da Evolução como um paradigma para a nossa existência, inspirando John Holland a desenvolver os Algoritmos Genéticos. Atualmente, com o grande crescimento da demanda no transporte aéreo, o homem volta seus esforços na busca por soluções que garantam a segurança da sociedade. Recentemente o pesquisador Naufal reuniu todos esses conceitos e desenvolveu um Modelo de Otimização de Demanda para o setor aeronáutico. Tal modelo visa amenizar a carga de trabalho dos controladores de tráfego aéreo na busca por aumentar a qualidade do serviço prestado por esse profissional, garantindo dessa forma níveis aceitáveis de segurança. Embora o modelo tenha se mostrado eficiente, ele apresentou uma deficiência quanto aos tempos despendidos para alcançar bons resultados. Na tentativa de otimizar os tempos do modelo atual, este trabalho de pesquisa adicionou o conceito de pressão seletiva, que representa a influência do meio ambiente. A representação da influência que o meio ambiente tem dentro da teoria da evolução de Darwin pode gerar uma implementação mais realista dos algoritmos genéticos. Este trabalho propõe a aplicação dos métodos de controle da pressão seletiva como alternativa de diminuir os tempos despendidos pelo modelo de otimização de demanda na busca por aumentar a segurança do setor aeroviário. / The search for understanding and copying the magnificent world that surrounds us has made man curious by nature. Santos Dumont achieved one of man?s most ancient dreams, to fly. Charles Darwin wrote the Theory of Evolution as a paradigm of our existence, inspiring John Holland to develop genetic algorithms. Presently, because of the growth of demand in air transportation, men concentrate their efforts in the search for solutions that can guarantee the safety of our society. Recently, researcher Naufal has gathered all these concepts and developed a Demand Optimization Model for the aeronautical sector. This model aims to ease the workload of air traffic controllers, in a search for increasing the quality of this service and guaranteeing acceptable levels of safety. Although his model has proved to be efficient, it has presented a weak point when it comes to time spent to reach good results. In an attempt to optimize time in the existing model, this research added the concept of selective pressure, which represents the influence of the environment. The representation of the influence that the environment has inside Darwin?s Theory of Evolution can generate a more realistic implementation of genetic algorithms. This work proposes an application of selective pressure control methods as an alternative to diminish time spent by the Demand Optimization Model in a search for increasing safety for the aeronautical sector.
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Computational Biology: Insights into Hemagglutinin and Polycomb Repressive Complex 2 FunctionJanuary 2012 (has links)
Influenza B virus hemagglutinin (HA) is a major surface glycoprotein with frequent amino-acid substitutions. However, the roles of antibody selection in the amino-acid substitutions of HA were still poorly understood. An analysis was conducted on a total of 271 HA 1 sequences of influenza B virus strains isolated during 1940∼2007 finding positively selected sites all located in the four major epitopes (120-loop, 150-loop, 160-loop and 190-helix) supporting a predominant role of antibody selection in HA evolution. Of particular significance is the involvement of the 120-loop in positive selection. Influenza B virus HA continues to evolve into new sublineages, within which the four major epitopes were targeted selectively in positive selection. Thus, any newly emerging strains need to be placed in the context of their evolutionary history in order to understand and predict their epidemic potential. As key epigenetic regulators, polycomb group (PcG) proteins are responsible for the control of cell proliferation and differentiation as well as stem cell pluripotency and self-renewal. To facilitate experimental identification of PcG target genes, which are poorly understood, we propose a novel computational method, EpiPredictor , which models transcription factor interaction using a non-linear kernel. The resulting targets suggests that multiple transcription factor networking at the cis -regulatory elements is critical for PcG recruitment, while high GC content and high conservation level are also important features of PcG target genes. To try to translate the EpiPredictor into human data, we performed a computational study utilizing 22 human genome-wide CHIP data to identify DNA motifs and genome features that would potentially specify PRC2 using five motif discovery algorithms, Jaspar known transcription binding motifs, and other whole genome data. We have found multiple motifs within the various subgroups of experimental categories that have much higher enrichment against CHIP identified gene promoter than among random gene promoters. Specifically, we have identified Low CpG content CpG Islands (LeG's) as being critical in the separation of Cancer cell line identified targets from Embryonic Stem cell line identified targets. Additionally, there are differences between human and mouse ES cell predictions using the same motifs and features suggesting relevant evolutionary divergence.
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Adaptation through a Stochastic Evolutionary Neuron Migration ProcessHaverinen, J. (Janne) 23 March 2004 (has links)
Abstract
Artificial Life is an interdisciplinary scientific and engineering enterprise investigating the fundamental properties of living systems through the simulation and synthesis of life-like processes in artificial media. One of the avenues of investigation is autonomous robots and agents.
Mimicking of the growth and adaptation of a biological neural circuit in an artificial medium is a challenging task owing to our limited knowledge of the complex process taking place in a living organism. By combining several developmental mechanisms, including the chemical, mechanical, genetic, and electrical, researchers have succeeded in developing networks with interesting topology, morphology, and function within Artificial Computational Chemistry. However, most of these approaches still fail to create neural circuits able to solve real problems in perception and robot control.
In this thesis a phenomenological developmental model called a Stochastic Evolutionary Neuron Migration Process (SENMP) is proposed. Employing a spatial encoding scheme with lateral interaction of neurons for artificial neural networks, which represent candidate solutions within a neural network ensemble, neurons of the ensemble form problem-specific spatial patterns with the desired dynamics as they migrate under the selective pressure.
The approach is applied to gain new insights into development, adaptation and plasticity in neural networks and to evolve purposeful behaviors for mobile robots. In addition, the approach is used to study the relationship of spatial patterns, composed of interacting entities, and their dynamics.
The feasibility and advantages of the approach are demonstrated by evolving neural controllers for solving a non-Markovian double pole balancing problem and by evolving controllers that exhibit navigation behavior for simulated and real mobile robots in complex environments. Preliminary results regarding the behavior of the adapting neural network ensemble are also shown and, particularly, a phenomenon exhibiting Hebbian-like dynamics.
This thesis is a step toward a long range goal that aims to create an intelligent robot that is capable of learning complex skills and adapts rapidly to environmental changes.
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Uso de simbiótico para descolonização de pacientes hospitalizados portadores de bacilos Gram-negativos multidrogarresistentes / Use of a symbiotic product to decolonize patients harboring multidrug-resistant Gram-negative bacilliHeluany Filho, Mário Augusto 10 June 2016 (has links)
Nas últimas décadas, a incidência de infecções hospitalares causadas por bactérias Gramnegativas multidrogarresistentes (MDR) vem crescendo de maneira vertiginosa em todo o mundo, de modo que a Organização Mundial de Saúde (OMS) recentemente reconheceu essas infecções como uma preocupação mundial devido ao seu impacto negativo sobre as taxas de mortalidade intra-hospitalar e dos custos da assistência à saúde, afetando tanto os países desenvolvidos quanto os em desenvolvimento. Atualmente considera-se que a higienização das mãos, o uso racional de antimicrobianos e o isolamento de contato são as principais medidas disponíveis para contenção desse avanço. Porém, elas são apenas parcialmente efetivas e de implementação trabalhosa e onerosa. Assim, considera-se necessário o desenvolvimento de formas mais simples e eficientes paralidar com esse problema. No presente estudo, nos propusemos a avaliar o impacto da administração de um produto simbiótico a pacientes colonizados e/ou infectados por bactérias Gram-negativas MDR sobre as taxas de descolonização desses patógenos no trato digestivo. Trata-se de um ensaio clínico randomizado, duplamente cego, controlado com placebo, envolvendo 101 pacientes hospitalizados com colonização prévia por bactérias Gram-negativas MDR, demonstrada por meio de cultura seletiva de swab retal, cuja intervenção consistiu na administração oral ou enteral diária de 1010 unidades de Lactobacillus bulgaricus e 1010 unidades de Lactobacillus rhamnosus associados a fruto-oligossacarídeos durante (FOS) 7 dias. O desfecho primário do estudo foi a descolonização completa do trato digestivo posterior à intervenção, que, na análise do tipo \"intenção de tratar modificada\" foi de 16,7% (8/48) no grupo experimental e 20,7% (11/53) no grupo controle (p=0,600). Na análise \"per protocol\", a descolonização completa do trato observada foi de 18,9% (7/37) no grupo experimental e 23,3% (7/30) no grupo controle (p=0,659). Em uma análise multivariada por meio de modelo de regressão logística o uso do simbiótico não influenciou significativamente o risco de descolonização completa do trato digestivo (OR= 0,80, IC 95%= 0,28-2,27, p= 0,678). A ocorrência de eventos adversos de natureza leve a moderada foi semelhante entre os grupos: 7,55% no grupo que utilizou placebo e 6,25% no grupo sob intervenção (p= 1,000). Nenhum evento adverso grave potencialmente relacionado às medicações de estudo foi observado. Nas condições estudadas, os dados obtidos pelo estudo nos levam à conclusão de que o simbiótico estudado demonstrou-se inefetivo na descolonização do trato digestivo de pacientes previamente colonizados por bactérias Gram-negativas MDR. / In recent decades the incidence of multidrug resistant (MDR) Gram-negative nosocomial infections has been dramatically raising in the whole world. The World Health Organization (WHO) recently recognized nosocomial infections due to MDR pathogens as a global concern due to its negative impact on patients, health-care workers and health-care institutions, affecting developed countries as well as developing ones. They negatively impact in-hospital mortality and health-care related costs. Hand hygiene promotion, antibiotic stewardship and contact precautions are the main available measures to control such MDR Gram-negative organisms in hospitals. However, they are only partially effective as well as difficult to be implemented and expensive. Therefore, simpler and more effective actions are thought to be helpful and urgent. In the present study, we analyzed the impact of the administration of a symbiotic product on patients harboring Gram-negative multidrug-resistant bacteria upon the subsequent rates of decolonization of these pathogens from the gastro-intestinal tract.This is a double-blinded and placebo controlled randomized clinical trial evaluating the oral/enteral daily administration of 1010 units of Lactobacillus bulgaricusplus 1010 units of Lactobacillus rhamnosus associated with fructo-oligosacharide (FOS), or placebo, for 7 days, to 101 patients previously colonized by MDR Gram-negative bacteria, identified through selective culture of rectal swab. The primary study outcome was the rate of complete decolonization of the MDR microorganism from the gastro-intestinal tract following the intervention. In the \"modified intention to treat\" analysis, decolonization rates observed were 16.7% (8/48) in the experimental group and 20.7% (11/53) in the placebo group (p=0,600). In the \"per protocol\" analysis, decolonization rates were 18.9% (7/37) in the experimental group and 23.3% (7/30) in the placebo group (p=0,659). In a logistic regression model, symbiotic use did not produce any impact on the chance of decolonization (OR=0.80, CI95%=0.28-2.27, p=0.678). Mild to moderate adverse events occured similarly in both the placebo (7.55%) and the experimental group (6.25%), (p=1,000). No severe adverse event potentially related to the medications was detected during the study period. In the present study conditions, the results obtained lead to the conclusion that the studied symbiotic proved to be ineffective to decolonize patients harboring multidrug resistant Gram-negative bacilli.
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Uso de simbiótico para descolonização de pacientes hospitalizados portadores de bacilos Gram-negativos multidrogarresistentes / Use of a symbiotic product to decolonize patients harboring multidrug-resistant Gram-negative bacilliMário Augusto Heluany Filho 10 June 2016 (has links)
Nas últimas décadas, a incidência de infecções hospitalares causadas por bactérias Gramnegativas multidrogarresistentes (MDR) vem crescendo de maneira vertiginosa em todo o mundo, de modo que a Organização Mundial de Saúde (OMS) recentemente reconheceu essas infecções como uma preocupação mundial devido ao seu impacto negativo sobre as taxas de mortalidade intra-hospitalar e dos custos da assistência à saúde, afetando tanto os países desenvolvidos quanto os em desenvolvimento. Atualmente considera-se que a higienização das mãos, o uso racional de antimicrobianos e o isolamento de contato são as principais medidas disponíveis para contenção desse avanço. Porém, elas são apenas parcialmente efetivas e de implementação trabalhosa e onerosa. Assim, considera-se necessário o desenvolvimento de formas mais simples e eficientes paralidar com esse problema. No presente estudo, nos propusemos a avaliar o impacto da administração de um produto simbiótico a pacientes colonizados e/ou infectados por bactérias Gram-negativas MDR sobre as taxas de descolonização desses patógenos no trato digestivo. Trata-se de um ensaio clínico randomizado, duplamente cego, controlado com placebo, envolvendo 101 pacientes hospitalizados com colonização prévia por bactérias Gram-negativas MDR, demonstrada por meio de cultura seletiva de swab retal, cuja intervenção consistiu na administração oral ou enteral diária de 1010 unidades de Lactobacillus bulgaricus e 1010 unidades de Lactobacillus rhamnosus associados a fruto-oligossacarídeos durante (FOS) 7 dias. O desfecho primário do estudo foi a descolonização completa do trato digestivo posterior à intervenção, que, na análise do tipo \"intenção de tratar modificada\" foi de 16,7% (8/48) no grupo experimental e 20,7% (11/53) no grupo controle (p=0,600). Na análise \"per protocol\", a descolonização completa do trato observada foi de 18,9% (7/37) no grupo experimental e 23,3% (7/30) no grupo controle (p=0,659). Em uma análise multivariada por meio de modelo de regressão logística o uso do simbiótico não influenciou significativamente o risco de descolonização completa do trato digestivo (OR= 0,80, IC 95%= 0,28-2,27, p= 0,678). A ocorrência de eventos adversos de natureza leve a moderada foi semelhante entre os grupos: 7,55% no grupo que utilizou placebo e 6,25% no grupo sob intervenção (p= 1,000). Nenhum evento adverso grave potencialmente relacionado às medicações de estudo foi observado. Nas condições estudadas, os dados obtidos pelo estudo nos levam à conclusão de que o simbiótico estudado demonstrou-se inefetivo na descolonização do trato digestivo de pacientes previamente colonizados por bactérias Gram-negativas MDR. / In recent decades the incidence of multidrug resistant (MDR) Gram-negative nosocomial infections has been dramatically raising in the whole world. The World Health Organization (WHO) recently recognized nosocomial infections due to MDR pathogens as a global concern due to its negative impact on patients, health-care workers and health-care institutions, affecting developed countries as well as developing ones. They negatively impact in-hospital mortality and health-care related costs. Hand hygiene promotion, antibiotic stewardship and contact precautions are the main available measures to control such MDR Gram-negative organisms in hospitals. However, they are only partially effective as well as difficult to be implemented and expensive. Therefore, simpler and more effective actions are thought to be helpful and urgent. In the present study, we analyzed the impact of the administration of a symbiotic product on patients harboring Gram-negative multidrug-resistant bacteria upon the subsequent rates of decolonization of these pathogens from the gastro-intestinal tract.This is a double-blinded and placebo controlled randomized clinical trial evaluating the oral/enteral daily administration of 1010 units of Lactobacillus bulgaricusplus 1010 units of Lactobacillus rhamnosus associated with fructo-oligosacharide (FOS), or placebo, for 7 days, to 101 patients previously colonized by MDR Gram-negative bacteria, identified through selective culture of rectal swab. The primary study outcome was the rate of complete decolonization of the MDR microorganism from the gastro-intestinal tract following the intervention. In the \"modified intention to treat\" analysis, decolonization rates observed were 16.7% (8/48) in the experimental group and 20.7% (11/53) in the placebo group (p=0,600). In the \"per protocol\" analysis, decolonization rates were 18.9% (7/37) in the experimental group and 23.3% (7/30) in the placebo group (p=0,659). In a logistic regression model, symbiotic use did not produce any impact on the chance of decolonization (OR=0.80, CI95%=0.28-2.27, p=0.678). Mild to moderate adverse events occured similarly in both the placebo (7.55%) and the experimental group (6.25%), (p=1,000). No severe adverse event potentially related to the medications was detected during the study period. In the present study conditions, the results obtained lead to the conclusion that the studied symbiotic proved to be ineffective to decolonize patients harboring multidrug resistant Gram-negative bacilli.
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