Pseudomonas aeruginosa β-lactamase induction requires two permeases, AmpG and AmpP

Background In Enterobacteriaceae, β-lactam antibiotic resistance involves murein recycling intermediates. Murein recycling is a complex process with discrete steps taking place in the periplasm and the cytoplasm. The AmpG permease is critical to this process as it transports N-acetylglucosamine anhydrous N-acetylmuramyl peptides across the inner membrane. In Pseudomonadaceae, this intrinsic mechanism remains to be elucidated. Since the mechanism involves two cellular compartments, the characterization of transporters is crucial to establish the link. Results Pseudomonas aeruginosa PAO1 has two ampG paralogs, PA4218 (ampP) and PA4393 (ampG). Topology analysis using β-galactosidase and alkaline phosphatase fusions indicates ampP andampG encode proteins which possess 10 and 14 transmembrane helices, respectively, that could potentially transport substrates. Both ampP and ampG are required for maximum expression of β-lactamase, but complementation and kinetic experiments suggest they act independently to play different roles. Mutation of ampG affects resistance to a subset of β-lactam antibiotics. Low-levels of β-lactamase induction occur independently of either ampP or ampG. Both ampG and ampP are the second members of two independent two-gene operons. Analysis of the ampG and ampPoperon expression using β-galactosidase transcriptional fusions showed that in PAO1, ampGoperon expression is β-lactam and ampR-independent, while ampP operon expression is β-lactam and ampR-dependent. β-lactam-dependent expression of the ampP operon and independent expression of the ampG operon is also dependent upon ampP. Conclusions In P. aeruginosa, β-lactamase induction occurs in at least three ways, induction at low β-lactam concentrations by an as yet uncharacterized pathway, at intermediate concentrations by an ampPand ampG dependent pathway, and at high concentrations where although both ampP and ampGplay a role, ampG may be of greater importance. Both ampP and ampG are required for maximum induction. Similar to ampC, ampP expression is inducible in an ampR-dependent manner. Importantly, ampP expression is autoregulated and ampP also regulates expression of ampG. Both AmpG and AmpP have topologies consistent with functions in transport. Together, these data suggest that the mechanism of β-lactam resistance of P. aeruginosa is distinct from well characterized systems in Enterobacteriaceae and involves a highly complicated interaction between these putative permeases and known Amp proteins.

Characterization of N-acylhomoserine lactone-degrading bacteria associated with the Zingiber officinale (ginger) rhizosphere: Co-existence of quorum quenching and quorum sensing in Acinetobacter and Burkholderia

Background Cell-to-cell communication (quorum sensing (QS)) co-ordinates bacterial behaviour at a population level. Consequently the behaviour of a natural multi-species community is likely to depend at least in part on co-existing QS and quorum quenching (QQ) activities. Here we sought to discover novelN-acylhomoserine lactone (AHL)-dependent QS and QQ strains by investigating a bacterial community associated with the rhizosphere of ginger (Zingiber officinale) growing in the Malaysian rainforest. Results By using a basal growth medium containing N-(3-oxohexanoyl)homoserine lactone (3-oxo-C6-HSL) as the sole source of carbon and nitrogen, the ginger rhizosphere associated bacteria were enriched for strains with AHL-degrading capabilities. Three isolates belonging to the generaAcinetobacter (GG2), Burkholderia (GG4) and Klebsiella (Se14) were identified and selected for further study. Strains GG2 and Se14 exhibited the broadest spectrum of AHL-degrading activities via lactonolysis while GG4 reduced 3-oxo-AHLs to the corresponding 3-hydroxy compounds. In GG2 and GG4, QQ was found to co-exist with AHL-dependent QS and GG2 was shown to inactivate both self-generated and exogenously supplied AHLs. GG2, GG4 and Se14 were each able to attenuate virulence factor production in both human and plant pathogens. Conclusions Collectively our data show that ginger rhizosphere bacteria which make and degrade a wide range of AHLs are likely to play a collective role in determining the QS-dependent phenotype of a polymicrobial community.

Capacity Investment in Renewable and Conventional Energy Sources

This dissertation studies capacity investments in energy sources, with a focus on renewable technologies, such as solar and wind energy. We develop analytical models to provide insights for policymakers and use real data from the state of Texas to corroborate our findings.

We first take a strategic perspective and focus on electricity pricing policies. Specifically, we investigate the capacity investments of a utility firm in renewable and conventional energy sources under flat and peak pricing policies. We consider generation patterns and intermittency of solar and wind energy in relation to the electricity demand throughout a day. We find that flat pricing leads to a higher investment level for solar energy and it can still lead to more investments in wind energy if considerable amount of wind energy is generated throughout the day.

In the second essay, we complement the first one by focusing on the problem of matching supply with demand in every operating period (e.g., every five minutes) from the perspective of a utility firm. We study the interaction between renewable and conventional sources with different levels of operational flexibility, i.e., the possibility

of quickly ramping energy output up or down. We show that operational flexibility determines these interactions: renewable and inflexible sources (e.g., nuclear energy) are substitutes, whereas renewable and flexible sources (e.g., natural gas) are complements.

In the final essay, rather than the capacity investments of the utility firms, we focus on the capacity investments of households in rooftop solar panels. We investigate whether or not these investments may cause a utility death spiral effect, which is a vicious circle of increased solar adoption and higher electricity prices. We observe that the current rate-of-return regulation may lead to a death spiral for utility firms. We show that one way to reverse the spiral effect is to allow the utility firms to maximize their profits by determining electricity prices.

Exploring molecular variation in Schistosoma japonicum in China

Schistosomiasis is a neglected tropical disease that affects more than 200 million people worldwide. The main disease-causing agents, Schistosoma japonicum, S. mansoni and S. haematobium, are blood flukes that have complex life cycles involving a snail intermediate host. In Asia, S. japonicum causes hepatointestinal disease (schistosomiasis japonica) and is challenging to control due to a broad distribution of its snail hosts and range of animal reservoir hosts. In China, extensive efforts have been underway to control this parasite, but genetic variability in S. japonicum populations could represent an obstacle to eliminating schistosomiasis japonica. Although a draft genome sequence is available for S. japonicum, there has been no previous study of molecular variation in this parasite on a genome-wide scale. In this study, we conducted the first deep genomic exploration of seven S. japonicum populations from mainland China, constructed phylogenies using mitochondrial and nuclear genomic data sets, and established considerable variation between some of the populations in genes inferred to be linked to key cellular processes and/or pathogen-host interactions. Based on the findings from this study, we propose that verifying intraspecific conservation in vaccine or drug target candidates is an important first step toward developing effective vaccines and chemotherapies against schistosomiasis.

Women's perceptions of Nurse-Midwives' caring behaviours during perinatal loss in Lilongwe, Malawi: An Exploratory study

Objective The Objective for this study was to explore women’s perceptions of and satisfaction with nursing care they received following stillbirth and neonatal death in villages around a community hospital in Lilongwe. Methods This qualitative, exploratory study through a mixture of purposive and snowball sampling, recruited 20 women who had lost a child through stillbirth or neonatal death in the past 2 years. Data were collected through semi-structured interviews in the privacy of the homes of the women. All interviews were tape-recorded and transcribed verbatim and were analyzed using thematic analysis. Results Almost half of the respondents expressed satisfaction with the way nurses cared for them after experiencing perinatal loss, although some felt unable to comment on the quality of care received. However, several bereaved women were dissatisfied with how nurses handled their loss. They noted nurses not providing attention or explanations and some even attributed the death of their child to nurses’ neglect. Conclusions Interventions are needed which foster awareness where nurses become more sensitive to the mothers’ emotional needs in an equally sensitive health care system. There is also need for more research into care provided following perinatal deaths in resource-poor settings to increase the evidence-base for informed and improved care for women who have experienced child loss.

Pharmacists’ knowledge and perception of topical antibacterial drug dispensing in community pharmacy setting in Kedah, Malaysia

Purpose: To assess Pharmacists’ Perceptions and Experiences of Topical Antibacterial Drug Dispensing in Community Pharmacy Setting in Kedah State, Malaysia in order to minimize drug resistance issues. Methods: A cross-sectional study involving a pre-validated questionnaire was conducted in community pharmacies within Kedah State, Malaysia. Descriptive statistics and Spearman’s correlation coefficient were used for data analysis. The collected were analysed using statistical package for social sciences (SPSS) version 18.0. Results: The result shows that, 53.4 % of CPs in Kedah State perceived that topical antibacterial is not necessary for every topical bacterial infection. Fusidic acid was the most frequently dispensed topical antibacterial drug while superficial wound was reported to be the most frequently encountered topical bacterial infection. CPs (12.60 %) encountered antibacterial resistance cases but none reported them. The drug that had resistance issue was neomycin. Conclusion: CPs in Kedah State, Malaysia generally have the right perceptions on the dispensing of topical antibacterial drugs. However, their knowledge on the rational use of topical antibacterial drugs and vigilance on antibacterial resistance issue need improvement.

Large-scale screening of a targeted Enterococcus faecalis mutant library identifies envelope fitness factors

Spread of antibiotic resistance among bacteria responsible for nosocomial and community-acquired infections urges for novel therapeutic or prophylactic targets and for innovative pathogen-specific antibacterial compounds. Major challenges are posed by opportunistic pathogens belonging to the low GC% gram-positive bacteria. Among those, Enterococcus faecalis is a leading cause of hospital-acquired infections associated with life-threatening issues and increased hospital costs. To better understand the molecular properties of enterococci that may be required for virulence, and that may explain the emergence of these bacteria in nosocomial infections, we performed the first large-scale functional analysis of E. faecalis V583, the first vancomycin-resistant isolate from a human bloodstream infection. E. faecalis V583 is within the high-risk clonal complex 2 group, which comprises mostly isolates derived from hospital infections worldwide. We conducted broad-range screenings of candidate genes likely involved in host adaptation (e.g., colonization and/or virulence). For this purpose, a library was constructed of targeted insertion mutations in 177 genes encoding putative surface or stress-response factors. Individual mutants were subsequently tested for their i) resistance to oxidative stress, ii) antibiotic resistance, iii) resistance to opsonophagocytosis, iv) adherence to the human colon carcinoma Caco-2 epithelial cells and v) virulence in a surrogate insect model. Our results identified a number of factors that are involved in the interaction between enterococci and their host environments. Their predicted functions highlight the importance of cell envelope glycopolymers in E. faecalis host adaptation. This study provides a valuable genetic database for understanding the steps leading E. faecalis to opportunistic virulence.

Tjerita Dahoeloe Kala di Negri Tjina, Terpoengoet dari Tjerita'an Boekoe menjanji'an Tjina, Tan Sha-Gio Nio

Pages 23-25 are destroyed and supplemented from Tjerita Tan Sha-Go Nio swatoe tjerita jang amat indah dan rame, pada dzaman dahoeloe kalah die benoewa Tiong Kok (1920, publisher Ko Tjeng Bie, Batavia, 3rd print). Some pages may overlap, but story goes normally.

Validez de contenido de un cuestionario para evaluar las etapas del cambio de comportamiento en estilos de vida en escolares, Colombia: Estudio FUPRECOL

Estudio de validación en escolares pertenecientes a instituciones educativas oficiales de la ciudad de Bogotá, Colombia. Se diseñó y aplicó el CCC-FUPRECOL que indagó por las etapas de cambio para la actividad física/ejercicio, consumo de frutas, verduras, drogas, tabaco e ingesta de bebidas alcohólicas, de manera auto-diligenciada por formulario estructurado.

Elevación transitoria de TSH neonatal asociada a factores de riesgo de parto pretérmino

Introducción: La hipotiroxinemia es una alteración transitoria frecuente en el prematuro que resuelve sin medicación, es importante conocer los factores que se asocian con esta alteración para disminuir el tratamiento inoportuno y el aumento de costos en atención en salud que puede implicar un diagnóstico errado de hipotiroidismo congénito. Por medio de este estudio se evaluó la asociación entre elevación transitoria de la TSH neonatal y algunas variables asociadas a parto pretérmino en pacientes atendidos en la Clínica Materno Infantil Colsubsidio nacidos entre Enero 2014 a Abril de 2015. Metodología: Se realizó un estudio de casos y controles, analítico, retrospectivo. Los casos fueron prematuros con elevación de TSH sin hipotiroidismo congénito, los controles fueron prematuros con TSH normal, seleccionados de manera aleatoria 70 casos, 140 controles con una relación 1:2. Se realizaron asociaciones mediante prueba de chi cuadrado y análisis multivariado para controlar factores de confusión. Resultados: La edad gestacional promedio para casos fue 34.6±1.8, para controles 34.2±2.4. Ambas poblaciones fueron comparables. Los factores con resultados estadísticamente significativos fueron: Pielonefritis (p 0.04), hipertensión inducida por el embarazo (p 0.00), presencia de anemia (p 0.02) y embarazo múltiple (p0.03). Los resultados de regresión logística establecieron que la pielonefritis, hipertensión y anemia son factores de riesgo con resultados estadísticamente significativos. Discusión: Los resultados permitieron documentar que existen factores de riesgo para prematurez, como la pielonefritis, anemia materna e hipertensión inducida por el embarazo, que influyen en los valores de TSH de cordón umbilical que no necesariamente conllevan al desarrollo de hipotiroidismo congénito

Estudio de factibilidad de importación de calzado

Este proyecto de investigación es un estudio de factibilidad de importación del calzado para dama desde China para la empresa colombiana Kenzo Jeans a través del cual se evalúan a profundidad estrategias en producto, precio y distribución para que la empresa valore la conveniencia del proceso. El objetivo de esta investigación es generar herramientas y estrategias necesarias para que la empresa logre tener una visión más completa al importar calzado desde China para la distribución en el mercado colombiano. Este estudio se realizó con el fin de brindar información para que la gerencia pueda tomar decisiones correctas, eliminando el desconocimiento que pueda generar mayor incertidumbre al involucrarse en un proceso de importación. Para llevar a cabo este proceso se determinaron unos criterios de evaluación y selección mínimos respecto al diseño del producto, precio, calidad, número de unidades mínimas para realizar el pedido, empaque y etiquetado con el que debían contar los posibles proveedores en China. Esto se realizó a través de un acercamiento a los potenciales proveedores y permitió filtrar a aquellos que podrían cumplir con los criterios exigidos por Kenzo Jeans. Una vez realizado el proceso de clasificación y selección se logró determinar que existe potencial en la importación de calzado de dama desde China. Hecho este proceso se sugiere a Kenzo Jeans realizar contacto directo con estas empresas a través de un posible viaje de negocios.

Social competence at the playground: Preschoolers during recess

Social interactions at the playground have been represented as a rich learning opportunity to hone and master social skills at pre- school years. Specifically, all forms of social play (fantasy, role, ex- ercise or rough-and-tumble) have been related to children’s social competence. The main goal of this study was to examine whether it is a certain kind of social play which facilitates the development of social competence, or if it is just the opportunity for interacting during recess that provides children with an optimal environment for social learning. A total of 73 preschoolers (4–6 years old) were videotaped at the school’s playground. Teachers provided assess- ments of children’s social competence. Children’s interactions at the playground were assessed through an innovative measuring method, based on radio-frequency identification devices. The results showed a positive association between exercise play and children’s social competence. In contrast with the literature, both forms of pretend play, fantasy and role play were unrelated to children’s social competence. Smaller peer groups and longer interactions also demonstrated a positive association with these preschoolers’ social competence. The study shows the importance of outdoor physical play for preschoolers’ social success. More- over, the study suggests that the environment in which children play has an important effect on the adaptive nature of their play.

Social competence at the playground: Preschoolers during recess

Social interactions at the playground have been represented as a rich learning opportunity to hone and master social skills at preschool years. Specifically, all forms of social play (fantasy, role, exercise or rough-and-tumble) have been related to children’s social competence. The main goal of this study was to examine whether it is a certain kind of social play which facilitates the development of social competence, or if it is just the opportunity for interacting during recess that provides children with an optimal environment for social learning. A total of 73 preschoolers (4–6 years old) were videotaped at the school’s playground. Teachers provided assessments of children’s social competence. Children’s interactions at the playground were assessed through an innovative measuring method, based on radio-frequency identification devices. The results showed a positive association between exercise play and children’s social competence. In contrast with the literature, both forms of pretend play, fantasy and role play were unrelated to children’s social competence. Smaller peer groups and longer interactions also demonstrated a positive association with these preschoolers’ social competence. The study shows the importance of outdoor physical play for preschoolers’ social success. Moreover, the study suggests that the environment in which children play has an important effect on the adaptive nature of their play.

Total Quality Management and Corporate Social Responsibility. Literature review. The case of Nabeiro Delta Cafés Group

The relationship between the themes of Total Quality Management (TQM) and Social Responsibility (CSR) through the concepts, approaches and models of excellence is a reality of sustainable and stable companies. Being organizations, people, act correctly and rightly do in society go through a quality management and social responsibility thereof. It is based on these two philosophies (Total Quality Management and Corporate Social Responsibility), which developed this literature review work, essentially based on a relational analysis in two papers, namely: "TQM and CSR Nexus" by Ghobadian et al. (2007) and "The Corporate Social Responsibility Audit Within the Quality Management Framework," de Kok et al. (2001) and applied to an organizational situation in concrete: the Nabeiro Delta Cafés Group - SGPS, SA.