Clinical and Laboratory Development of Echinocandin Resistance in Candida glabrata: Molecular Characterization

The pathogenic yeast Candida glabrata has become a public health issue due to the increasing number of echinocandin resistant clinical strains reported. In this study, acquisition and development of resistance to this antifungal class were studied in serial C. glabrata isolates from five patients admitted in two Spanish hospitals with a resistant profile against echinocandins associated with different mutations in hot-spot 1 of FKS2 gene. For two of these patients susceptible FKS wild-type isolates obtained prior to resistant ones were also investigated. Isolates were genotyped using multilocus sequence typing and microsatellite length polymorphism techniques, which yielded comparable results. Susceptible and resistant isolates from the same patient had the same genotype, being sequence type (ST) 3 the most prevalent among them. Isolates with different FKS mutations but the same ST were present in the same patient. MSH2 gene alterations were also studied to investigate their correlation with antifungal resistance acquisition but no association was found with antifungal resistance nor with specific genotypes. In vitro exposure to increasing concentrations of micafungin to susceptible isolates developed colonies carrying FKS mutations in agar plates containing a minimum concentration of 0.06 mg/L of micafungin after less than 48 h of exposure. We investigated the correlation between development of resistance and genotype in a set of susceptible strains after being in vitro exposed to micafungin and anidulafungin but no correlation was found. Mutant prevention concentration values and spontaneous growth frequencies after selection with both echinocandins were statistically similar, although FKS mutant colonies were more abundant after micafungin exposure (p < 0.001). Mutation S663P and F659 deletion were the most common ones found after selection with both echinocandins.This work was supported by the Fondo de Investigación Sanitaria (Grant FI14CIII/00025 to OR-M and research projects PI13/02145 and PI16CIII/00035 to AA-I), and also supported by the Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16CIII/0004/0003) – co-financed by the European Development Regional Fund “A way to achieve Europe,” Operative Program Intelligent Growth 2014–2020.S

Age-Related Changes in Astrocytic and Ependymal Cells of the Subventricular Zone

Neurogenesis persists in the adult subventricular zone (SVZ) of the mammalian brain. During aging, the SVZ neurogenic capacity undergoes a progressive decline, which is attributed to a decrease in the population of neural stem cells (NSCs). However, the behavior of the NSCs that remain in the aged brain is not fully understood. Here we performed a comparative ultrastructural study of the SVZ niche of 2-month-old and 24-month-old male C57BL/6 mice, focusing on the NSC population. Using thymidine-labeling, we showed that residual NSCs in the aged SVZ divide less frequently than those in young mice. We also provided evidence that ependymal cells are not newly generated during senescence, as others studies suggest. Remarkably, both astrocytes and ependymal cells accumulated a high number of intermediate filaments and dense bodies during aging, resembling reactive cells. A better understanding of the changes occurring in the neurogenic niche during aging will allow us to develop new strategies for fighting neurological disorders linked to senescence

Multicenter study of lumen-apposing metal stents with or without pigtail in endoscopic ultrasound-guided biliary drainage for malignant obstruction - BAMPI TRIAL: an open-label, randomized controlled trial protocol

Background It is unclear whether the insertion of an axis-orienting double-pigtail plastic stent (DPS) through biliary lumen-apposing meal stent (LAMS) in EUS-guided choledochoduodenostomy (CDS) improves the stent patency. The aim of this study is to determine whether this technical variant offers a clinical benefit in EUS-guided biliary drainage (BD) for the management of distal malignant biliary obstruction. Methods/design This is a multicenter open-label, randomized controlled trial with two parallel groups. Eighty-four patients with malignant biliary obstruction will undergo EUS-BD (CDS type) using LAMS in 7 tertiary hospitals in Spain and will be randomized to the LAMS and LAMS plus DPS groups. The primary endpoint is the rate of recurrent biliary obstruction, as a stent dysfunction parameter, detected during follow-up. Secondary endpoints: technical and clinical success (reduction in bilirubin > 50% within 14 days of stent placement), safety, and others (number of reinterventions, time to biliary obstruction, prognostic factors, survival rate). Discussion The BAMPI trial has been designed to determine whether the addition of a coaxial axis-orienting DPS through LAMS is superior to LAMS alone to prevent stent dysfunction

A membrane computing simulator of trans-hierarchical antibiotic resistance evolution dynamics in nested ecological compartments (ARES)

In this article, we introduce ARES (Antibiotic Resistance Evolution Simulator) a software device that simulates P-system model scenarios with five types of nested computing membranes oriented to emulate a hierarchy of eco-biological compartments, i.e. a) peripheral ecosystem; b) local environment; c) reservoir of supplies; d) animal host; and e) host's associated bacterial organisms (microbiome). Computational objects emulating molecular entities such as plasmids, antibiotic resistance genes, antimicrobials, and/or other substances can be introduced into this framework and may interact and evolve together with the membranes, according to a set of pre-established rules and specifications. ARES has been implemented as an online server and offers additional tools for storage and model editing and downstream analysisThis work has also been supported by grants BFU2012-39816-C02-01 (co-financed by FEDER funds and the Ministry of Economy and Competitiveness, Spain) to AL and Prometeo/2009/092 (Ministry of Education, Government of Valencia, Spain) and Explora Ciencia y Explora Tecnologia/SAF2013-49788-EXP (Spanish Ministry of Economy and Competitiveness) to AM. IRF is recipient of a "Sara Borrell" postdoctoral fellowship (Ref. CD12/00492) from the Ministry of Economy and Competitiveness (Spain). We are also grateful to the Spanish Network for the Study of Plasmids and Extrachromosomal Elements (REDEEX) for encouraging and funding cooperation among Spanish microbiologists working on the biology of mobile genetic elements (Spanish Ministry of Science and Innovation, reference number BFU2011-14145-E).Campos Frances, M.; Llorens, C.; Sempere Luna, JM.; Futami, R.; Rodríguez, I.; Carrasco, P.; Capilla, R.... (2015). A membrane computing simulator of trans-hierarchical antibiotic resistance evolution dynamics in nested ecological compartments (ARES). Biology Direct. 10(41):1-13. https://doi.org/10.1186/s13062-015-0070-9S1131041Baquero F, Coque TM, Canton R. Counteracting antibiotic resistance: breaking barriers among antibacterial strategies. Expert Opin Ther Targets. 2014;18:851–61.Baquero F, Lanza VF, Canton R, Coque TM. Public health evolutionary biology of antimicrobial resistance: priorities for intervention. Evol Appl. 2014;8:223–39.Baquero F, Coque TM, de la Cruz F. 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Clin Microbiol Infect. 2012;18 Suppl 4:2–4.Kumsa B, Socolovschi C, Parola P, Rolain JM, Raoult D. Molecular detection of Acinetobacter species in lice and keds of domestic animals in Oromia Regional State. Ethiopia PLoS One. 2012;7:e52377.Ahmad A, Ghosh A, Schal C, Zurek L. Insects in confined swine operations carry a large antibiotic resistant and potentially virulent enterococcal community. BMC Microbiol. 2011;11:23.Graczyk TK, Knight R, Gilman RH, Cranfield MR. The role of non-biting flies in the epidemiology of human infectious diseases. Microbes Infect. 2001;3:231–5.Limoee M, Enayati AA, Khassi K, Salimi M, Ladonni H. Insecticide resistance and synergism of three field-collected strains of the German cockroach Blattella germanica (L.) (Dictyoptera: Blattellidae) from hospitals in Kermanshah, Iran. Trop Biomed. 2011;28:111–8.Salehzadeha A, Tavacolb P, Mahjubc H. Bacterial, fungal and parasitic contamination of cockroaches in public hospitals of Hamadan, Iran. J Vect Borne Dis. 2007;44:105–10.Akinjogunla OJ, Odeyemi AT, Udoinyang EP. Cockroaches (periplaneta americana and blattella germanica): reservoirs of multi drug resistant (MDR) bacteria in Uyo, Akwa Ibom State. Scientific J Biol Sci. 2012;1:19–30.Mideo N, Alizon S, Day T. Linking within- and between-host dynamics in the evolutionary epidemiology of infectious diseases. Trends Ecol Evol. 2008;23:511–7.Gillings MR, Stokes HW. Are humans increasing bacterial evolvability? Trends EcolEvol. 2012;27:346–52.Baquero F. Environmental stress and evolvability in microbial systems. Clin Microbiol Infect. 2009;15 Suppl 1:5–10.Paun G, Rozemberg G, Salomaa A. The Oxford Handbook of Membrane Computing. Oxford, London. Oxford University Press. 2010.Paun G. Membrane Computing. An Introduction. Berlin, Heidelberg. Springer-Verlag GmbH. 2002.Paun G. Computing with membranes. J Comput Syst Sci. 2000;61:108–43.Fontana F, Biancom L, Manca V. P systems and the modeling of biochemical oscillations. Lect Notes Comput Sci. 2006;3850:199–208.Cheruku S, Paun A, Romero-Campero FJ, Perez-Jimenez MJ, Ibarra OH. Simulating FAS-induced apoptosis by using P systems. Prog Nat Sci. 2007;4:424–31.Perez-Jimenez MJ, Romero-Campero FJ. P systems, a new computational modelling tool for systems biology. Transactions on computational systems. Lect N Bioinformat. 2006;Biology VI:176–97.Romero-Campero FJ, Perez-Jimenez MJ. Modelling gene expression control using P systems: The Lac Operon, a case study. Biosystems. 2008;91:438–57.Romero-Campero FJ, Perez-Jimenez MJ. A model of the quorum sensing system in Vibrio fischeri using P systems. Artif Life. 2008;14:95–109.Besozzi D, Cazzaniga P, Pescini D, Mauri G. Modelling metapopulations with stochastic membrane systems. Biosystems. 2008;91:499–514.Cardona M, Colomer MA, Perez-Jimenez MJ, Sanuy D, Margalida A. Modelling ecosystems using P Systems: The Bearded Vulture, a case of study. 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Effect of supercritical conditions on the transalkylation of diethylbenzene with benzene

The use of supercritical fluids in hydrocarbons transformation reactions shows important advantages: increase of reaction rate and selectivity as well as increase of the catalyst lifetime in the supercritical region with respect to the subcritical one. The objective of this work was to study the effect of supercritical conditions on the transalkylation of diethylbenzene with benzene to produce ethylbenzene. Both CO2 and free-solvent systems, using different acidic commercial zeolites (Beta, Y and Mordenite) as catalyst, have been explored. For all the catalysts, supercritical conditions improved the catalyst performance only in the free-solvent system, results which have been explained in terms of the different densities and diethylbenzene diffusion coefficients of the reaction mixture. © 2005 Elsevier B.V. All rights reserved

Trial-to-trial variability in evoked neural responses exhibit a very low frequency temporal signature - a magnetoencephalography study

In functional magnetic resonance (fMRI) studies, the blood oxygen level dependent (BOLD) signal displays intrinsic spontaneous and task-independent very low frequency (VLF) oscillations (&lt; 0.1 Hz). Most prominent during rest, when they persist into task sessions they can predict trial-to-trial variability in both evoked behavior and brain responses by providing a baseline onto which deterministic responses elicited by the task are superimposed. Moreover, evidence in the literature tentatively suggests that this VLF activity may not be present in the data as distinct, independent source(s) per se, but rather as a mechanism that modulates and perhaps even governs underlying brain processes. Here, we use electrophysiology to investigate the intertrial variability observed in magnetoencephalographic (MEG) event-related field (ERF) components, and to examine whether this variability exhibits a VLF time signature in order to indirectly infer information about the underlying slow waves. The focus is on the visual component, the M100, understood to be regulated by attention. We also explored whether individual differences in the M100 VLF pattern varies as a function of attention deficit/hyperactivity disorder (ADHD) by comparing 11 cases against 11 controls. The M100 component was extracted from the data using a recently introduced blind-source separation technique – space-time independent component analysis (ST-ICA) – which allowed trial-by-trial analysis to be performed on the M100 for proper assessment of VLF modulation. Our results demonstrate, for the first time, the ability of this signal-processing method to isolate relevant components from multidimensional, noisy, ERF data recorded from a highly dense 148-channel MEG system. The intertrial variability in the amplitude and latency of the M100 responses exhibits a slow wave pattern (&lt; 0.1 Hz). However, there was no evidence that the degree of VLF modulation was different in ADHD participants. The role of this VLF activity in brain function is discussed

Melatonin enhances neural stem cell differentiation and engraftment by increasing mitochondrial function

Mendivil-Perez, Miguel et al.Neural stem cells (NSCs) are regarded as a promising therapeutic approach to protecting and restoring damaged neurons in neurodegenerative diseases (NDs) such as Parkinson's disease and Alzheimer's disease (PD and AD, respectively). However, new research suggests that NSC differentiation is required to make this strategy effective. Several studies have demonstrated that melatonin increases mature neuronal markers, which reflects NSC differentiation into neurons. Nevertheless, the possible involvement of mitochondria in the effects of melatonin during NSC differentiation has not yet been fully established. We therefore tested the impact of melatonin on NSC proliferation and differentiation in an attempt to determine whether these actions depend on modulating mitochondrial activity. We measured proliferation and differentiation markers, mitochondrial structural and functional parameters as well as oxidative stress indicators and also evaluated cell transplant engraftment. This enabled us to show that melatonin (25 μM) induces NSC differentiation into oligodendrocytes and neurons. These effects depend on increased mitochondrial mass/DNA/complexes, mitochondrial respiration, and membrane potential as well as ATP synthesis in NSCs. It is also interesting to note that melatonin prevented oxidative stress caused by high levels of mitochondrial activity. Finally, we found that melatonin enriches NSC engraftment in the ND mouse model following transplantation. We concluded that a combined therapy involving transplantation of NSCs pretreated with pharmacological doses of melatonin could efficiently restore neuronal cell populations in PD and AD mouse models depending on mitochondrial activity promotion.This study was partially funded by the following grants: SAF2009-14037 from the Spanish Ministry of Economy and Competitivity (MINECO), CB/10/00238 from the Carlos III Health Institute, GREIB.PT_2010_04 from the CEIBiotic Program of the University of Granada, Spain, and CTS-101 from the Innovation, Science and Business Council, Junta de Andalucía, Spain. The study was carried out within the framework of the “Convenio Marco 206-2012” agreement between the University of Antioquia in Colombia and the University of Granada in Spain. MJ-Del-Rio and CV-P were supported by Colciencias grants #1115-657-740786 (contract 623-2014). MM-P and V-SM are associate researchers. MM-P is funded by the Colciencias, Enlaza-Mundos, and AUIP mobility programs. VS-M was funded by the AUIP mobility program.Peer Reviewe

Object Representation and Comparison Inferred from Its Medial Axis

International audienceThe skeleton and its associated medial axis give a very compact representation of objects, even in the case of complex shapes and topologies. They are powerful shape descriptors, bridging the gap between low-level and highlevel object representations. Surprisingly, skeletons have been used in a relatively small number of applications. This work deals with the question of using the potential strength of the skeleton and the medial axis. From the medial axis, we build adequate attributed relational graphs to organize in a structured way informations about object shape and topology contained in the medial axis. This representation then permits to compare in a meaningful way various objects using a graph matching algorithm. Synthetic results are presented

Batterer intervention programs in Spain: The professionals perspective

The Organic Law 1/2004 of 28 December on Integrated Protection Measures against Gender Violence has had, among other consequences, the generalization of intervention programs for batterers in cases of gender violence. The objective of this research is to explore the point of view of specialized professionals about these programs. For this purpose a qualitative methodology was used, by applying semi-structured interviews to 65 key informants, i.e. professionals with experience in implementing and/or managing and evaluating such programs. In general, these professionals were satisfied with the programs in which they had participated and they valued them positively. They considered that certain characteristics of participants and of the programs themselves contribute to promoting or hindering their success and also that they could obtain better results by customizing interventions. These results provide valuable information for understanding the difficulties encountered in implementing these programs and to improve them