Authority, collective learning and agentic action in teaching : tracing a pedagogy from Franz Fanon

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Polyclonal KPC-3-producing Enterobacteriaceae in Portugal

Water has been recognized as a reservoir for antibiotic resistance genes (ARG), where the presence of mobile genetic elements, including plasmids, favors their dissemination. It is noteworthy that nonpathogenic environmental organisms, where plasmids encoding multiple ARG are prevalent, can provide resistance to most classes of antimicrobials including beta-lactams, aminoglycosides, chloramphenicol, trimethoprim, streptomycin, fosfomycin, quinolones, among others. The main goal of this study was to evaluate the presence of ARGs, related with -lactam and quinolone resistance, in Gram-negative bacteria isolates from surface and raw and treated waste water environments. Water samples were collected from different environments within an urban water cycle in the region of Northern Portugal, which included treated and raw wastewater, water to the consumers and water surface. Screening of antimicrobial susceptibility of 56 Gram-negative isolates (20 Escherichia coli, 8 Citrobacter spp., 7 Klebsiella spp., 6 Kluyvera spp., 4 Sphingomonas panni, 2 Enterobacter spp., 1 Acinetobacter johnsonii, 3 Aeromonas veronii, 1 Hafnia alvei, 1 Pantoea agglomerans, 1 Roultella ornithinolytica, 1 Serratia sp., 1 Stenotrophomonas maltophilia), identified by 16S rRNA gene sequencing analysis using universal primers, was performed by disk diffusion method. Interpretative reading of susceptibilities allowed to direct the search for antibiotic resistant genes. PCR and sequencing were used to screen and identify beta-lactamase- and plasmidmediated quinolone resistance (PMQRs)-encoding genes. All isolates were also screened for the presence of class 1 integrons. PCR-based replicon typing (PBRT) was used to type the resistance plasmids of the blaGES-5- producing isolate among the major incompatibility (Inc) groups, specifically FIA, FIB, FIC, HI1, HI2, I1-I , L/M, N, P, W, T, A/C, K, B/O, X, Y, F, and FIIA. Multilocus sequence typing (MLST) of the GES-5 K. pneumoniae-producing isolate was performed according to the Institute Pasteur scheme (http://www.pasteur.fr/recherche/genopole/PF8/mlst/Kpneumoniae.html). Overall, 16/56 isolates were multidrug-resistant (MDR), i.e. presenting a reduced susceptibility to 3 or more structurally unrelated antibiotics, suggesting a great diversity of resistance mechanisms. Noteworthy, 10 isolates (4 S. panni, 1 A. johnsonii, 3 A. veronii, 1 K. pneumoniae, and 1 S. maltophilia) showed nonsusceptibility to carbapenems, which constitutes one of the last resorts on the antimicrobial therapy. Their phenotypic and molecular characterization revealed the expression of several enzymes: the naturally occurring carbapenemase in one S. maltophilia, ImiS in three A. veronii, both MBLs, and OXA-type carbapenemase in one A. johnsonii, responsible for their intrinsic resistance; the class A GES-5-producing K. pneumoniae isolate belonged to a novel MLST sequence type, the ST961 (18-22-18-90-142-13-179). PBRT of the plasmid-carrying blaGES-5 gene showed that it did not belong to any of the Inc groups tested. No carbapenemases were found in the 4 S. panni isolates. The beta-lactam resistance, carbapenem susceptibility, found in 33 isolates was justified by the presence of various Class A (12 blaTEM-1 with distinct promoters, 6 blaSHV) and different Class C -lactamase-encoding genes (blaCMY, blaACC, blaACT), some here firstly described: blaCMY-65 (JF780936), blaCMY-89 (HE819403), blaCMY-90 (HE819404), blaACT-13 (HE819402) and blaACC-5 (HE819401). Class 1 integrons were detected among 6 of TEM- 1-producing isolates. Together, the beta-lactamases identified explain the level of beta-lactam resistance. Besides quinolone resistance detected, none PMQR were identified, suggesting chromosomal alterations in the quinolone resistance-determining region. This study identified ARGs related not only to commonly used antibiotics, but also to carbapenems, providing, at our knowledge, the first description of a GES-5-producing Enterobacteriaceae recovered in an environmental setting. The study highlights the need of surveillance of these antibiotic resistance mechanisms in environmental backgrounds, since it represents a liable reservoir of potential pathogenic resistant bacteria. Worryingly, recent studies demonstrated that while the WWTP reduced the bacterial load, the treatment is inefficient to remove antibiotic resistant bacteria

Carbapenemase-producing Enterobacteriaceae isolates collected in Portuguese hospitals

Objectives: In Portugal, little is known on carbapenemase (CARB)-producing Enterobacteriaceae. The aim of this study was to identify the resistance mechanisms of Enterobacteriaceae isolates, identified at hospital laboratories as carbapenem (CA) non-susceptible. Methods: This study included 61 Enterobacteriaceae isolates (26 Klebsiella spp, 15 Escherichia coli, 9 Enterobacter spp, 6 Morganella morgannii, 4 Proteus mirabilis, 1 Serratia marcescens), collected between 04/2006 and 09/2011 and sent to the NIH-Lisbon for CA susceptibility confirmation. Antimicrobial susceptibility of clinical isolates was performed by disk diffusion method (CA-SFM). Clinical isolates showing synergism between CA and boronic acid (BOR) (and/or clavulanic acid, CLAV) or with EDTA were considered presumptively CARB-producers from class A or Class B, respectively. PCR and sequencing were applied to detect and identify CARB-encoding genes; the respective genetic environment was revealed by sequencing using PCR mapping. Direct transfer of the CA resistance phenotype was attempted by mating-out assays. Antibiotics susceptibility (MIC) of transconjugants and respective isolates were tested by microdilution. Results: The majority of isolates were collected from the urine (57.4%) of elderly (≥65 years old) male patients (54.1%), admitted at the emergency room/ambulatory (24.6%) and at internal medicine (18.0%) wards. Among all isolates, 50.8% were nonsusceptible to at least one CA, being 67.2% multidrug-resistant; 16 isolates showed synergy between CA and BOR (and/or CLAV). Among those, 5 were KPC-3-producers (4 Klebsiella pneumoniae and 1 Enterobacter clocae), collected in 2010 (2) and 2011 (3). The blaKPC-3 genes were confirmed to be carried by plasmids. Genetic environment of blaKPC-3 gene revealed the presence of a Tn4401 transposon in all but one isolate (E. cloacae), suggesting that this last gene was included in other Tn4401-like isoform. We also detected a VIM-2-producing Klebsiella oxytoca, collected in 2009, among the 7 isolates that showed synergy between imipinem and EDTA. No blaGES, blaNDM or blaIMP were detected. Conclusion: In conclusion, this study provides new data regarding the molecular epidemiology of CARB-producing Enterobacteriaceae in Portugal. Overall, our results emphasize the need of a concerted action to manage CA use. This is supported by EARS-Net, which reported an increase in CA nonsusceptibility of K. pneumoniae isolates from 0.72% in 2008 to 1.58% in 2010

Glycosylation as a Main Regulator of Growth and Death Factor Receptors Signaling

Glycosylation is a very frequent and functionally important post-translational protein modification that undergoes profound changes in cancer. Growth and death factor receptors and plasma membrane glycoproteins, which upon activation by extracellular ligands trigger a signal transduction cascade, are targets of several molecular anti-cancer drugs. In this review, we provide a thorough picture of the mechanisms bywhich glycosylation affects the activity of growth and death factor receptors in normal and pathological conditions. Glycosylation affects receptor activity through three non-mutually exclusive basic mechanisms: (1) by directly regulating intracellular transport, ligand binding, oligomerization and signaling of receptors; (2) through the binding of receptor carbohydrate structures to galectins, forming a lattice thatregulates receptor turnover on the plasma membrane; and (3) by receptor interaction with gangliosides inside membrane microdomains. Some carbohydrate chains, for example core fucose and \u3b21,6-branching, exert a stimulatory effect on all receptors, while other structures exert opposite effects on different receptors or in different cellular contexts. In light of the crucial role played by glycosylation in the regulation of receptor activity, the development of next-generation drugs targeting glyco-epitopes of growth factor receptors should be considered a therapeutically interesting goal

Wake skew angle variation with rotor thrust for wind turbines in yaw based on the MEXICO experiment

The primary objective of the MEXICO (Model Experiments in Controlled Conditions) project was to generate experimental data from which the uncertainties of the computational tools employed to predict wind turbine performance and loads. Pressure sensors were used for pressure measurements while PIV was used with the major aim of tracking the tip vortex trajectory. The aerodynamic forces on the blades were derived found from the pressure measurements and were used in an inverse free wake lifting line model to compute the positions of the tip vortices. From these the wake skew angle was derived. A relationship between the skew angle and the thrust coefficient was thus drawn.peer-reviewe

Cost-effective energy and carbon emissions optimization in building renovation (annex 56): executive summary for policy makers

This guidebook was compiled to raise awareness among the players that can influence policies and standard definition and to engage them in the subjects of energy efficiency and renewable energy sources in the context of building renovation. Existing buildings present a tremendous potential, not only to reduce energy use and emissions, but also on other areas of the political agenda. It is the objective of this guidebook to highlight how energy related building renovation is a policy tool to achieve broad benefits to societyinfo:eu-repo/semantics/publishedVersio

Molecular survey of carbapenem resistant Enterobacteriaceae isolates from Portuguese Hospitals: co-production of carbapenemase KPC-3 and the efflux pump OqxAB

Objectives: Although there are important studies regarding the different carbapenemase (CARB)-producing Gram-negative bacteria, little is known concerning their molecular epidemiology in Portugal. The main aim of this study was to characterize, by phenotype and molecular typing methods, CARB-producing Enterobacteriaceae isolates recovered from Portuguese health care institutions, and evaluate its impact on treatment strategy. Methods: This study included 2105 clinical isolates, collected between April/2006 and February/2013, in different Portuguese healthcare institutions. Screening of antimicrobial susceptibility was performed by disc diffusion method. Clinical isolates with resistance or with decreased susceptibility to ertapenem were considered presumptively CARB-producers; in these isolates, PCR and sequencing were applied to detect and identify CARB-encoding genes, as well as other bla and plasmid-mediated quinolone resistance (PMQRs) genes. MICs of CARB-producing isolates were tested by microdilution (EUCAST breakpoints). The plasmids obtained from clinical isolates were characterized by PCR-based replicon typing (PBRT). Clonal relatedness of K. pneumoniae isolates was investigated by multilocus sequence typing (MLST), using the protocol developed by the Institute Pasteur (www.pasteur.fr/mlst/Kpneumoniae.html). Results: Among the 2105 isolates tested, 165 (7.8%) were putative CARB-producers and were selected for further analysis. Thirty-five (21.2%) of the 165 positive isolates were confirmed to be CARB-producers, of which the majority were collected from the urine (54.3%) of elderly (≥65 years old) male patients (54.3%), and admitted at the emergency room/ambulatory (22.9%) or internal medicine (17.1%) wards. All were multidrug-resistant, with nonsusceptibility to at least one carbapenem, and with consistent susceptibility only to colistin. In those isolates was detected the following beta-lactamases: 30 KPC-3 (22 K. pneumoniae, 3 Escherichia coli, 2 Enterobacter aerogenes and 3 Enterobacter clocae), 4 GES-5 (K. pneumoniae) and one VIM-2 (Klebsiella oxytoca). CARB-encoding genes were present alone or in combination with other bla genes, such as blaSHV-12, blaSHV-14, blaSHV-26, blaSHV-36, blaCTX-M-15, and the blaSHV-164. PMQR-encoding genes were also detected, namely qnrA, qnrB, aac(6’)-Ib-cr and the recently identified oqxAB. All blaKPC-3 genes were located on a Tn3-based transposon, Tn4401, while blaGES-5 and blaVIM-2 genes were associated with class 3 and 1 integrons, respectively. In our study, the majority of the blaCARB-harbouring plasmids were nonconjugative, having been typed as IncFrepB by PBRT. Clonal relatedness of the 26 K. pneumoniae isolates, obtained by MLST, showed that they were from distinct STs, namely ST14, ST15, ST34, ST59, ST147, ST416, ST698, and from the two novels ST: ST960 and, among all, the predominant ST1138 (corresponding to KPC-3 plus SHV-36 producers). Conclusion: In conclusion, this study provides new data regarding the molecular epidemiology of CARB-producing Enterobacteriaceae, which appears to be widespread in Portugal. Dissemination of blaCARB seems to be due to carriage of similar CARB-harbouring plasmids within genetically diverse clinical strains. Overall, our results emphasize the need of a concerted action to manage carbapenem use

Cost-effective energy and carbon emissions optimization in building renovation (annex 56): guidebook for professional home owners

This guidebook is particularly intended for professional home-owners, i.e. individuals or companies that own and manage residential buildings. It is assumed that these owners are responsible for ensuring maintenance, repair and general servicing tasks and lead the decisions on the improvements to be made regarding comfort, safety, saving energy or just uplifting the buildings to contemporary needs or style. The main goal is to help in the decision-making process towards the optimized renovation of the residential building stock. More specifically, the guidebook provides a framework for the understanding of the relationships between cost-effective building renovation, energy savings and the use of renewable energy sources, highlighting the total added value achieved with the interventions.info:eu-repo/semantics/publishedVersio