Over expression of AdeABC and AcrAB-TolC efflux systems confers tigecycline resistance in clinical isolates of Acinetobacter baumannii and Klebsiella pneumoniae

Abstract: INTRODUCTION: Due to the wide use of tigecycline in the treatment of severe infections caused by multidrug-resistant (MDR) bacteria, clinical resistance to tigecycline has increased in recent years. Here, we investigated the relationship between tigecycline resistance and the expression of efflux pumps. METHODS: Clinical isolates of Acinetobacter baumannii and Klebsiella pneumoniae were consecutively collected from hospitalized patients in three hospitals. The minimum inhibitory concentration (MIC) of tigecycline was determined using the broth microdilution method. Expression levels of efflux pump genes and regulators were examined by quantitative real-time reverse transcription polymerase chain reaction. The correlations between tigecycline MICs and gene expression levels were analyzed. RESULTS: Overall, 1,026 A. baumannii and 725 K. pneumoniae strains were collected. Most strains were isolated from sputum. The tigecycline resistance rate was 13.4% in A. baumannii isolates and 6.5% in K. pneumoniae isolates. Overexpression of AdeABC and AcrAB-TolC efflux systems was observed found in clinical tigecycline-resistant isolates. The tigecycline MIC had a linear relationship with the adeB expression level in A. baumannii isolates, but not with the acrB expression level in K. pneumoniae isolates. There were significant linear trends in the overexpression of ramA as the tigecycline MIC increased in K. pneumoniae isolates. CONCLUSIONS: Tigecycline resistance in A. baumannii and K. pneumoniae was strongly associated with the overexpression of efflux systems. More studies are needed to elucidate whether there are other regulators that affect the expression of adeB in A. baumannii and how ramA affects the expression of acrB in K. pneumoniae.

Nanomedicines, a strategy to evade multidrug resistance

Multidrug resistance is a major problems associated with cancer chemotherapy. Efflux transports is one of the numerous mechanisms involved in multidrug resistance. P-glycoprotein is a transmembrane protein, responsible for drug efflux, which decreases drugs intracellular bioavailability, consequently decreasing their efficacy against cancer. Cancer growth and dissemination depends on the expression of transcriptional factors such as, Twist. Among other features, this protein is related with cells chemoresistance possible by regulation of multidrug resistance pathways including the P-glycoprotein expression. The herein study proposes to demonstrate if paclitaxel entrapped nanoparticles is an effective system in evading multidrug resistance mechanisms and if functionalization of a specific antibody against cancer stem cells receptors (anti-CD44v6) has the capability to target selectively these cells increasing nanoparticles efficacy. Therefore solid lipid nanoparticles were prepared and a breast cancer cell line (MDA-MB-436) was exposed to them in order to assess unloaded nanoparticles cytotoxic effects, increased pharmacologic efficacy of loaded nanoparticles relative to the free drug and their ability to evade multidrug resistance. The proposed solid lipid nanoparticles system proved to be capable of efficiently evading multidrug resistance mechanisms; however no improvement was added when these nanoparticles were functionalized with the antibody in the in vitro studies. However, the nanoparticles system is effective against multidrug resistance mechanisms.

Lightweight adjustable partition system: evaluation of resistance to horizontal loads and functional failure from impacts

This paper presents and discusses the results of the serviciability and use condition tests carried on an innovative solution for partitions, designated AdjustMembrane developed within a research project. The proposed system is a modular non-loadbearing wall, tensioned between the pavements and ceiling slabs, which are used as anchoring elements. It allows several advantages, related with the weight reduction to achieve a good sustainable performance, such as the reduction of construction costs, energy, and materials, and it is easy to recycle and to reuse, allowing self-construction. Apart from a general presentation of the partition technology, this paper presents and discusses the results of experimental tests carried out. From the results obtained, it is possible to conclude that the solution fulfils the requirements for this typology of wall in terms of resistance to horizontal loads induced by soft and hard body impacts.

Assessment of the effectiveness of steel fibre reinforcement for the punching resistance of flat slabs by experimental research and design approach

The present paper deals with the experimental assessment of the effectiveness of steel fibre reinforcement in terms of punching resistance of centrically loaded flat slabs, and to the development of an analytical model capable of predicting the punching behaviour of this type of structures. For this purpose, eight slabs of 2550 x 2550 x 150 mm3 dimensions were tested up to failure, by investigating the influence of the content of steel fibres (0, 60, 75 and 90 kg/m3) and concrete strength class (50 and 70 MPa). Two reference slabs without fibre reinforcement, one for each concrete strength class, and one slab for each fibre content and each strength class compose the experimental program. All slabs were flexurally reinforced with a grid of ribbed steel bars in a percentage to assure punching failure mode for the reference slabs. Hooked ends steel fibres provided the unique shear reinforcement. The results have revealed that steel fibres are very effective in converting brittle punching failure into ductile flexural failure, by increasing both the ultimate load and deflection, as long as adequate fibre reinforcement is assured. An analytical model was developed based on the most recent concepts proposed by the fib Mode Code 2010 for predicting the punching resistance of flat slabs and for the characterization of the behaviour of fibre reinforced concrete. The most refined version of this model was capable of predicting the punching resistance of the tested slabs with excellent accuracy and coefficient of variation of about 5%.

Comparison of different numerical methods for the solution of the time-fractional reaction-diffusion equation with variable diffusion coefficient

In this work we perform a comparison of two different numerical schemes for the solution of the time-fractional diffusion equation with variable diffusion coefficient and a nonlinear source term. The two methods are the implicit numerical scheme presented in [M.L. Morgado, M. Rebelo, Numerical approximation of distributed order reaction- diffusion equations, Journal of Computational and Applied Mathematics 275 (2015) 216-227] that is adapted to our type of equation, and a colocation method where Chebyshev polynomials are used to reduce the fractional differential equation to a system of ordinary differential equations

Using polymers to improve the rutting resistance of asphalt concrete

This study assesses rutting on two types of modified asphalt mixtures containing: (i) amorphous polyolefin polymer and (ii) a particular polymer obtained by combining LDPE (low density polyethylene) and EVA (ethyl-vinyl-acetate). Rutting tests were performed by a wheel tracking device. Stiffness and fatigue tests were carried out to confirm the performance of the asphalt mixtures. The testing showed that polymer modification in this study improved rut resistance without compromising the stiffness and fatigue behavior. The rutting results were fit in the NCHRP 1-37A model and the in situ rutting performance of asphalt mixtures can be predicted.

Assessment of the mechanical performance of recycled unbound materials for pavement subbase layers

The cyclic load triaxial test is a laboratory test that allows studying the mechanical behaviour of unbound granular materials used in base/subbase layers of road pavements. The resilient modulus and permanent strains are required as inputs in structural pavement design. This paper presents some results obtained for recycled materials (crushed concrete aggregate and blended crushed waste aggregate), with a view to promoting their use in pavement structures. Results relating to a reference material (limestone) are also presented, for comparison. All the test results discussed in this paper were obtained in variable cyclic radial pressure (VCP) tests. The tests performed (VCP) aim to study the influence of water content on the resilient modulus of recycled materials, as well as on the resistance to permanent deformation. Using the experimental data as a basis, further modelling work was carried out to establish the stresses developing in base/capping layers in typical Belgian road pavements. These numerical results allow to propose some simplifications of the stress paths applied in the testing procedures and to establish a new test protocol that also considers compaction during construction works. The results of this research work provide an excellent set of findings for the mechanical characterization of unbound base materials through the cyclic triaxial test, and contribute to a better understanding and correct application of recycled materials under geotechnical engineering background

Introducing resistance genes against ToMV, TYLCV and TSWV infections in two tomato varieties (Muchamiel and De la Pera)

Dissertação de mestrado em Biologia Molecular, Biotecnologia e Bioempreendedorismo em Plantas

Cost efficiency and resistance to chemical attack of a fly ash geopolymeric mortar versus epoxy resin and acrylic paint coatings

This article presents results of an experimental investigation on the resistance to chemical attack (with sulphuric, hydrochloric and nitric acid) of several materials: OPC concrete, high-performance concrete, epoxy resin, acrylic painting and a fly ash-based geopolymeric mortar). Three types of acids with three high concentrations (10, 20 and 30%) were used to simulate long-term degradation. A cost analysis was also performed. The results show that the epoxy resin has the best resistance to chemical attack independently of the acid type and the acid concentration. However, the cost analysis shows that the epoxy resin-based solution is the least cost-efficient solution being 70% above the cost efficiency of the fly ash-based geopolymeric mortar.

The diagnostic and prognostic role of liquid-based cytology: are we ready to monitor therapy and resistance?

Here, we evaluate the diagnostic and prognostic role of liquid-based cytology (LBC) in different body lesions, including thyroid, lung, effusions and malignant breast lesions. LBC has gained consensus after being applied to both non-gynecologic and fine-needle aspiration cytology. Although some remain sceptical regarding the diagnostic efficacy of LBC, mainly when used alone, in recent years, good results have been obtained as long as it showed a high diagnostic accuracy. Here, we discuss the additional possibility of storing material for the application of ancillary techniques (immunocytochemistry–molecular analysis) with several diagnostic and prognostic advantages, which may pave the way for the challenging evaluation of both monitoring responses to treatment and resistance to targeted therapies in thyroid, lung, breast carcinoma or malignant effusions. Furthermore, it provides the use of several molecular spots as specific targets for personalized therapy.

Durabilidade de colagens estruturais em elementos de madeira

Dissertação de mestrado integrado em Engenharia Civil

Predicting SO2 pollution incidents by means of additive models with optimum variable selection

The aim of this paper is to predict time series of SO2 concentrations emitted by coal-fired power stations in order to estimate in advance emission episodes and analyze the influence of some meteorological variables in the prediction. An emission episode is said to occur when the series of bi-hourly means of SO2 is greater than a specific level. For coal-fired power stations it is essential to predict emission epi- sodes sufficiently in advance so appropriate preventive measures can be taken. We proposed a meth- odology to predict SO2 emission episodes based on using an additive model and an algorithm for variable selection. The methodology was applied to the estimation of SO2 emissions registered in sampling lo- cations near a coal-fired power station located in Northern Spain. The results obtained indicate a good performance of the model considering only two terms of the time series and that the inclusion of the meteorological variables in the model is not significant.

Influence of oxygen conditions on bacterial interactions within biofilms related with cystic fibrosis

Dissertação de mestrado em Bioengineering