Reappraisal of the outcome of healthcare-associated and community-acquired bacteramia: a prospective cohort study

Background: Healthcare-associated (HCA) bloodstream infections (BSI) have been associated with worse outcomes, in terms of higher frequencies of antibiotic-resistant microorganisms and inappropriate therapy than strict community-acquired (CA) BSI. Recent changes in the epidemiology of community (CO)-BSI and treatment protocols may have modified this association. The objective of this study was to analyse the etiology, therapy and outcomes for CA and HCA BSI in our area. Methods: A prospective multicentre cohort including all CO-BSI episodes in adult patients was performed over a 3-month period in 2006–2007. Outcome variables were mortality and inappropriate empirical therapy. Adjusted analyses were performed by logistic regression. Results: 341 episodes of CO-BSI were included in the study. Acquisition was HCA in 56% (192 episodes) of them. Inappropriate empirical therapy was administered in 16.7% (57 episodes). All-cause mortality was 16.4% (56 patients) at day 14 and 20% (71 patients) at day 30. After controlling for age, Charlson index, source, etiology, presentation with severe sepsis or shock and inappropriate empirical treatment, acquisition type was not associated with an increase in 14-day or 30-day mortality. Only an stratified analysis of 14th-day mortality for Gram negatives BSI showed a statically significant difference (7% in CA vs 17% in HCA, p = 0,05). Factors independently related to inadequate empirical treatment in the community were: catheter source, cancer, and previous antimicrobial use; no association with HCA acquisition was found. Conclusion: HCA acquisition in our cohort was not a predictor for either inappropriate empirical treatment or increased mortality. These results might reflect recent changes in therapeutic protocols and epidemiological changes in community pathogens. Further studies should focus on recognising CA BSI due to resistant organisms facilitating an early and adequate treatment in patients with CA resistant BSI

Discovery of potent and selective inhibitors of the Escherichia coli M1-aminopeptidase via multicomponent solid-phase synthesis of tetrazole-peptidomimetics

The Escherichia coli neutral M1-aminopeptidase (ePepN) is a novel target identified for the development of antimicrobials. Here we describe a solid-phase multicomponent approach which enabled the discovery of potent ePepN inhibitors. The on-resin protocol, developed in the frame of the Distributed Drug Discovery (D3) program, comprises the implementation of parallel Ugi-azide four-component reactions with resin-bound amino acids, thus leading to the rapid preparation of a focused library of tetrazole-peptidomimetics (TPMs) suitable for biological screening. By dose-response studies, three compounds were identified as potent and selective ePepN inhibitors, as little inhibitory effect was exhibited for the porcine ortholog aminopeptidase. The study allowed for the identification of the key structural features required for a high ePepN inhibitory activity. The most potent and selective inhibitor (TPM 11) showed a non-competitive inhibition profile of ePepN. We predicted that both diastereomers of compound TPM 11 bind to a site distinct from that occupied by the substrate. Theoretical models suggested that TPM 11 has an alternative inhibition mechanism that doesn't involve Zn coordination. On the other hand, the activity landscape analysis provided a rationale for our findings. Of note, compound TMP 2 showed in vitro antibacterial activity against Escherichia coli. Furthermore, none of the three identified inhibitors is a potent haemolytic agent, and only two compounds showed moderate cytotoxic activity toward the murine myeloma P3X63Ag cells. These results point to promising compounds for the future development of rationally designed TPMs as antibacterial agents

Dolor crónico: relación con sintomatología prefrontal y estrés percibido

ABSTRACT Objective: The quality of perceived stress coping in chronic pain is related to the performance of the prefrontal cortex as the main structure of control and coordination of superior behavior control. The present study explores the presence of prefrontal symptomatology, in the form of problems to manage cognition, emotions and behavior, and perceived stress in a sample of people suffering from chronic pain. Material and methods: We studied 78 participants with a diagnosis of chronic pain ranging in age from 27 to 81 years (mean 54.2 and d.t 13.4). Sociodemographic and clinical variables were analyzed together with the results in the 11-item Short Brief Pain Questionnaire (CBD) to assess the intensity and interference of pain, the Prefrontal Symptom Inventory (ISP), both in its complete version of 46 items and in the abbreviated of 20, and the 10-itme Perceived Scale of Perceived Stress (EEP). Results and discussion: Significant correlations between the prefrontal symptomatology and the intensity (r = 0.32) and the interference (r = 0.53) of the pain, as well as between the stress and the interference of the pain in the mood (r = 0.36). People report more painful feelings when they refer more cognitive and emotional management problems surrounding the environment. The general interference of pain is related to more motivational and attention problems, while the interference that the pain produces in the mood also increases the problems with executive and emotional control. A preliminary structural equation explaining the effect is proposed. Conclusion: The data suggest that the stress perceived by people with chronic pain depends on the inability of the prefrontal cortex to cope with a changing or threatening situation and this problem is fed back over and over as the person is less able to cope with the environment. Therefore, comprehensive treatment of chronic pain should include psychological interventions focused on coping with stress and cognitive optimization of skills related to prefrontal functioning.RESUMEN Objetivo: La calidad del afrontamiento del estrés percibido en el dolor crónico está relacionada con el rendimiento de la corteza prefrontal como estructura principal de control y coordinación de control superior de la conducta. El presente trabajo estudia la presencia de sintomatología prefrontal, en forma de problemas para gestionar la cognición, las emociones y el comportamiento, y de estrés percibido en una muestra de personas que sufren dolor crónico. Material y métodos: Se estudiaron 78 participantes con diagnóstico de dolor crónico con edades comprendidas entre 27 y 81 años (media 54,2 y d.t. 13,4). Se analizaron variables sociodemográficas y clínicas junto con los resultados en el Cuestionario Breve de Dolor (CBD) abreviado de 11 ítems para valorar la intensidad e interferencia de dolor, el Inventario de Síntomas Prefrontales (ISP), tanto en su versión completa de 46 ítems como en la abreviada de 20, y la Escala de Estrés Percibido (EEP) abreviada de 10 ítems. Resultados y discusión: Aparecen correlaciones significativas entre la sintomatología prefrontal y la intensidad (r = 0,32) y la interferencia (r = 0,53) del dolor, así como entre el estrés y la interferencia del dolor en el estado del ánimo (r = 0,36). Las personas declaran más sensación dolorosa cuando refieren más problemas de gestión cognitiva y emocional del entorno que las rodea. La interferencia general del dolor se relaciona con más problemas motivacionales y de atención, mientras que la interferencia que el dolor produce en el estado del ánimo incrementa, además, los problemas con el control ejecutivo y emocional. Se propone una ecuación estructural preliminar explicativa del efecto. Conclusión: Los datos sugieren que el estrés percibido por las personas con dolor crónico depende de la incapacidad de la corteza prefrontal para afrontar una situación cambiante o amenazante, y este problema se retroalimenta una y otra vez al ser la persona cada vez menos capaz de afrontar el ambiente. Por tanto, el tratamiento integral del dolor crónico debe incluir intervenciones psicológicas centradas en el afrontamiento del estrés y la optimización cognitiva de las habilidades relacionadas con el funcionamiento prefrontal

La tormenta tropical Delta y su transición extratropical en las cercanías de Canarias

Ponencia presentada en: XXIX Jornadas Científicas de la AME y el VII Encuentro Hispano Luso de Meteorología celebrado en Pamplona, del 24 al 26 de abril de 2006

A novel biocompatible polymer derived from D-mannitol used as a vector in the field of genetic engineering of eukaryotic cells

The design and preparation of new vectors to transport genetic material and increase the transfection efficiency continue being an important research line. Here, a novel biocompatible sugar-based polymer derived from D-mannitol has been synthesized to be used as a gene material nanocarrier in human (gene transfection) and microalga cells (transformation process). Its low toxicity allows its use in processes with both medical and industrial applications. A multidisciplinary study about the formation of polymer/p-DNA polyplexes has been carried out using techniques such as gel electrophoresis, zeta potential, dynamic light scattering, atomic force microscopy, and circular dichroism spectroscopy. The nucleic acids used were the eukaryotic expression plasmid pEGFP-C1 and the microalgal expression plasmid Phyco69, which showed different behaviors. The importance of DNA supercoiling in both transfection and transformation processes was demonstrated. Better results were obtained in microalga cells nuclear transformation than in human cells gene transfection. This was related to the plasmid's conformational changes, in particular to their superhelical structure. It is noteworthy that the same nanocarrier has been used with eukaryotic cells from both human and microalga.This work was supported by the Consejería de Conocimiento, Innovación y Universidades de la Junta de Andalucía (FQM-206, FQM-274, FQM-135 and P20–01234); VI Plan Propio Universidad de Sevilla (PP2019/00000748), and the European Union (Feder Funds).Peer reviewe

Supplementary material. A novel biocompatible polymer derived from D-mannitol used as a vector in the field of genetic engineering of eukaryotic cells

S1. Experimental Section: S1.1. Synthesis and Characterization Data. S1.2. Fluorescence Measurements. S1.3. Zeta Potential Measurements. S1.4. Dynamic Light Scattering Measurements. S1.5. Circular Dichroism Spectra. S1.6. Agarose Gel Electrophoresis. S1.7. Atomic Force Microscopy (AFM). S1.8. In Vitro Assays S1.9. Transfection Assays. S1.10. Chlamydomonas reinhardtii Nuclear Transformation. S2. Results and Discussion: S2.1. Characterization of Monomers and Polyurethanes. S2.2. Formation of the polyplexes PUMan/ctDNA. Figures: Fig. S1. FTIR spectra of PUMan and (MBocCis)DTDI. Fig. S2. SEC chromatogram of (MAL)DTDI. Fig. S3. SEC chromatogram of (MBocCis)DTDI. Fig. S4. SEC chromatogram of PUMan. Fig. S5. 1H NMR of (MAL)DTDI. Fig. S6. 1H NMR of (MBocCis)DTDI. Fig. S7. 1H NMR of PUMan. Fig. S8. TGA curve of PUMan. Fig. S9. Plot of EB emission intensities at different N/P values, circular dichroism spectra, zeta potential and hydrodynamic diameters of the PUMan-based polyplexes. Fig.S10. Electrophoresis of polyplexes PUMan/digested pEGFP-C1 and PUMan/digested Phyco69 at different N/P ratios. Fig.S11. Percentage of GFP positive cells after transfection with 3 μg of the plasmid pEGFP-C1 with the indicated reagents. The molar ratio PUMan:FuGENE and PUMan:DOPE was 1:1. Tables: Table S1. Thermal properties of PUMan and its precursors.Peer reviewe

Bovine Tuberculosis in Doñana Biosphere Reserve: The Role of Wild Ungulates as Disease Reservoirs in the Last Iberian Lynx Strongholds

Doñana National Park (DNP) in southern Spain is a UNESCO Biosphere Reserve where commercial hunting and wildlife artificial feeding do not take place and traditional cattle husbandry still exists. Herein, we hypothesized that Mycobacterium bovis infection prevalence in wild ungulates will depend on host ecology and that variation in prevalence will reflect variation in the interaction between hosts and environmental risk factors. Cattle bTB reactor rates increased in DNP despite compulsory testing and culling of infected animals. In this study, 124 European wild boar, 95 red deer, and 97 fallow deer were sampled from April 2006 to April 2007 and analyzed for M. bovis infection. Modelling and GIS were used to identify risk factors and intra and inter-species relationships. Infection with M. bovis was confirmed in 65 (52.4%) wild boar, 26 (27.4%) red deer and 18 (18.5%) fallow deer. In the absence of cattle, wild boar M. bovis prevalence reached 92.3% in the northern third of DNP. Wild boar showed more than twice prevalence than that in deer (p<0.001). Modelling revealed that M. bovis prevalence decreased from North to South in wild boar (p<0.001) and red deer (p<0.01), whereas no spatial pattern was evidenced for fallow deer. Infection risk in wild boar was dependent on wild boar M. bovis prevalence in the buffer area containing interacting individuals (p<0.01). The prevalence recorded in this study is among the highest reported in wildlife. Remarkably, this high prevalence occurs in the absence of wildlife artificial feeding, suggesting that a feeding ban alone would have a limited effect on wildlife M. bovis prevalence. In DNP, M. bovis transmission may occur predominantly at the intra-species level due to ecological, behavioural and epidemiological factors. The results of this study allow inferring conclusions on epidemiological bTB risk factors in Mediterranean habitats that are not managed for hunting purposes. Our results support the need to consider wildlife species for the control of bTB in cattle and strongly suggest that bTB may affect animal welfare and conservation

AFLP analysis reveals high genetic diversity but low population structure in Coccidioides posadasiiisolates from Mexico and Argentina

BACKGROUND: Coccidioides immitis and C. posadasii cause coccidioidomycosis, a disease that is endemic to North and South America, but for Central America, the incidence of coccidioidomycosis has not been clearly established. Several studies suggest genetic variability in these fungi; however, little definitive information has been discovered about the variability of Coccidioides fungi in Mexico (MX) and Argentina (AR). Thus, the goals for this work were to study 32 Coccidioides spp. isolates from MX and AR, identify the species of these Coccidioides spp. isolates, analyse their phenotypic variability, examine their genetic variability and investigate the Coccidioides reproductive system and its level of genetic differentiation. METHODS: Coccidioides spp. isolates from MX and AR were taxonomically identified by phylogenetic inference analysis using partial sequences of the Ag2/PRA gene and their phenotypic characteristics analysed. The genetic variability, reproductive system and level of differentiation were estimated using AFLP markers. The level of genetic variability was assessed measuring the percentage of polymorphic loci, number of effective allele, expected heterocygosity and Index of Association (I(A)). The degree of genetic differentiation was determined by AMOVA. Genetic similarities among isolates were estimated using Jaccard index. The UPGMA was used to contsruct the corresponding dendrogram. Finally, a network of haplotypes was built to evaluate the genealogical relationships among AFLP haplotypes. RESULTS: All isolates of Coccidioides spp. from MX and AR were identified as C. posadasii. No phenotypic variability was observed among the C. posadasii isolates from MX and AR. Analyses of genetic diversity and population structure were conducted using AFLP markers. Different estimators of genetic variability indicated that the C. posadasii isolates from MX and AR had high genetic variability. Furthermore, AMOVA, dendrogram and haplotype network showed a small genetic differentiation among the C. posadasii populations analysed from MX and AR. Additionally, the I(A) calculated for the isolates suggested that the species has a recombinant reproductive system. CONCLUSIONS: No phenotypic variability was observed among the C. posadasii isolates from MX and AR. The high genetic variability observed in the isolates from MX and AR and the small genetic differentiation observed among the C. posadasii isolates analysed, suggest that this species could be distributed as a single genetic population in Latin America

Population Genetic Structure of the Grasshopper Eyprepocnemis plorans in the South and East of the Iberian Peninsula

The grasshopper Eyprepocnemis plorans subsp. plorans harbors a very widespread polymorphism for supernumerary (B) chromosomes which appear to have arisen recently. These chromosomes behave as genomic parasites because they are harmful for the individuals carrying them and show meiotic drive in the initial stages of population invasion. The rapid increase in B chromosome frequency at intrapopulation level is thus granted by meiotic drive, but its spread among populations most likely depends on interpopulation gene flow. We analyze here the population genetic structure in 10 natural populations from two regions (in the south and east) of the Iberian Peninsula. The southern populations were coastal whereas the eastern ones were inland populations located at 260–655 m altitude. The analysis of 97 ISSR markers revealed significant genetic differentiation among populations (average GST = 0.129), and the Structure software and AMOVA indicated a significant genetic differentiation between southern and eastern populations. There was also significant isolation by distance (IBD) between populations. Remarkably, these results were roughly similar to those found when only the markers showing low or no dropout were included, suggesting that allelic dropout had negligible effects on population genetic analysis. We conclude that high gene flow helped this parasitic B chromosome to spread through most of the geographical range of the subspecies E. plorans plorans.This study was supported by a grant from the Spanish Ministerio de Ciencia e Innovación (CGL2009-11917), and was partially performed by FEDER funds. MIMP was supported by a fellowship (FPU) from the Spanish Ministerio de Ciencia e Innovación

Factors affecting survival in Mediterranean populations of the Eurasian eagle owl

The survival rate is a key parameter for population management and the monitoring of populations. Thus, an analysis of survival rate variations and the factors influencing the same is essential for understanding population dynamics. Here, we study the factors determining the survival and the causes of mortality of the Eurasian eagle owl (Bubo bubo) in two Spanish Mediterranean populations (Murcia and Seville) where the species has a high population density and breeding success; yet its survival rates and the factors that affect them are unknown. Between 2003 and 2010, 63 breeding owls were captured and radio-tracked. Three monthly (quarterly) survival rates were estimated using known-fate models in the program MARK. The mean overall annual survival rate was 0.776 (95 % CI: 0.677, 0.875). We observed survival differences between sexes, and between the breeding and non-breeding periods, although no overwhelming support was found for any particular model. We concluded that (i) females have a lower survival rate than males, probably due to their larger home ranges, which increase the risk of mortality; (ii) the survival rates of both sexes were lower during the non-breeding period; and (iii) the causes of mortality differed significantly between the two populations, gunshot being the main cause in Seville and electrocution in Murcia.Peer Reviewe