Effect of Different Media on the Bactericidal Activity of Colistin and on the Synergistic Combination With Azidothymidine Against mcr-1-Positive Colistin-Resistant Escherichia coli

Antimicrobial susceptibility testing (AST) performed according to defined guidelines is important to identify resistance and to predict the clinical success or failure of specific antibiotic therapy. However, these guidelines do not cover all physiological conditions that can have a tremendous impact on in vivo resistance. In this study, we tested the susceptibility of thirteen mcr-1-positive Escherichia coli strains against colistin, one of the last resort antibiotics for treating multi-drug resistant pathogens, in media recommended for ASTs as well as – physiologically more relevant – in human serum and artificial urine (AU). Minimal inhibitory concentration (MIC) values in heat-inactivated human serum were similar to those in cation-adjusted Mueller-Hinton broth (CAMHB), but reduced in native serum for almost all strains that could grow in this media. In AU MIC values for mcr-1 positive E. coli were increased significantly up to 16-fold compared to that in CAMBH, which did not apply to the colistin-susceptible E. coli strains tested. Although different growth media could affect the MIC of colistin alone, their impact on the synergistic effect of the combination with the antiviral drug azidothymidine was minimal. The higher divalent cation concentration combined with acidic pH values is most likely responsible for the increased MIC values of the mcr-1 harboring E. coli strains tested against colistin in AU compared to that in CAMHB. Antimicrobial susceptibility screening procedures for colistin using CAMHB only could lead to an underestimation of resistance under different physiological conditions. Therefore, not only pharmacokinetic but also pharmacodynamic studies in urine are as important as in serum or plasma

Serum bactericidal activity of colistin and azidothymidine combinations against mcr-1 positive colistin-resistant Escherichia coli.

To examine the serum bactericidal activity of colistin-sulphate (CS) and azidothymidine (AZT) combinations, time-kill curves were performed in native and heat-inactivated human serum with five colistin-resistant and four colistin-susceptible Gram-negative strains. The serum samples were spiked according to the median and minimum plasma peak concentrations measured in a phase 1 clinical study, in which seven healthy subjects received 3-times (q12) 1h-IV-infusions of 4, 2 and 2 million international units (MIU) colistin-methanesulfonate (CMS) co-administered with 200, 100 and 100 mg AZT, respectively. This trial was performed to assess the pharmacokinetics and safety of CMS/AZT-combination therapy. Minimal bactericidal concentrations of CS in native, but not heat-inactivated serum, were strongly reduced compared to Mueller-Hinton-Broth for all tested Enterobacteriaceae, except one colistin-resistant (serum-resistant) strain. For colistin-susceptible strains, the minimum CS concentration after 2 MIU CMS dosage was already bactericidal in native and heat-inactivated serum. Median, but not minimum, CS concentrations after 2 MIU CMS dosage were sufficient to kill the serum-resistant, colistin-resistant E.coli strain in native serum. In heat-inactivated serum, even the median CS concentration after 2 MIU CMS dosage was not bactericidal for all colistin-resistant strains. In general, combinations with AZT accelerated killing of colistin-resistant E.coli or showed bactericidal activity even if the substances alone were not bactericidal. Thus, the combination with AZT potentiates the bactericidal effect of colistin against colistin-resistant E.coli strains. Although the dosage of 2 MIU CMS plus AZT may be sufficient to treat infections with colistin-susceptible strains, for infections caused by colistin-resistant E.coli the dosing should be further optimized

Aberrant axillarybreast carcinoma: a case report andliterature review

Ectopic breast tissue (EBT) develops along the mammary line owing to incomplete embryologic regression of the mammary ridges. This includes supernumerary breasts and aberrant breast tissue, in which malignancy is rarely reported. The commonest site of ectopic breasts is at the axilla, and the subcutaneous axillary mass may pose a diagnostic challenge to theclinician. Case Report: We report the case of a 31 year old multiparous Nigerian woman who presented with a painless left axillary mass of two months' duration. The anatomical breasts were grossly and radiologically normal. A diagnosis of aberrant breast carcinoma in her left axilla was confirmed by tissue biopsy. She had wide local excision and left axillary dissection, followed by one course of cytotoxic chemotherapybeforeshe began radiotherapy. Conclusion: Malignancy of aberrant breast tissue is a rare entity. A high index of suspicion and a low threshold for biopsy of subcutaneous lesions in the periphery of the breast allows for early intervention and a better prognosis. Triple assessment with clinical, radiological and pathological assessment of lesions in the axilla or along the embryonic milk line can not be over-emphasized

Quantifying the effect of ecological restoration on runoff and sediment yields: A meta-analysis for the Loess Plateau of China

Ecological restoration can result in extensive land use transitions which may directly impact on water runoff and sediment loss and thus influence tradeoffs between multiple hydrological and soil ecosystem services. However, quantifying the effect of these transitions on runoff and sediment yields has been a challenge over large spatial scales. This study integrated and synthesized 43 articles and 331 runoff experimental plots in the Loess Plateau of China under natural rainfall to quantify the impacts of land use transitions on (a) runoff and sediment production, (b) runoff and soil loss reduction effectiveness, and (c) the tradeoffs between runoff and soil erosion. The effects of ecological restoration on runoff and sediment yields were quantified using a general mixed linear meta-regression model with a restricted maximum likelihood estimator on overall and individual ecological restoration types. The results showed that artificial grassland, forest, natural grassland, and shrubland had higher runoff and sediment reduction effectiveness. The annual runoff reduction effectiveness of the ecological restoration overall was 72.18% with the effects of artificial grassland, natural grassland, shrubland, and forest at 71.89%, 50.60%, 73.18%, and 73.08%, respectively. The annual sediment reduction effectiveness of the overall ecological restoration was 99.9% without a significant difference among the four land uses associated with ecological recovery. In addition, shrubland and forest significantly reduced sediment yields with relatively high runoff costs. Natural grassland was optimal for balancing water provisioning and soil conservation, and artificial grassland was second to natural grassland in this respect. Meanwhile, newly unmanaged abandoned land and cropland had relative weak functionality with regard to soil and water conservation. The implications of this study’s findings are discussed along with their potential to contribute to an improved understanding of the effects of ecological restoration on water supply and soil retention for the water-limited terrestrial ecosystem at a regional scale

A companion to a quasar at redshift 4.7

There is a growing consensus that the emergence of quasars at high redshifts is related to the onset of galaxy formation, suggesting that the detection of concentrations of gas accompanying such quasars should provide clues about the early history of galaxies. Quasar companions have been recently identified at redshifts up to $z \approx 3$. Here we report observations of Lyman-$\alpha$ emission (a tracer of ionised hydrogen) from the companion to a quasar at $z$=4.702, corresponding to a time when the Universe was less than ten per cent of its present age. We argue that most of the emission arises in a gaseous nebula that has been photoionised by the quasar, but an additional component of continuum light -perhaps quasar light scattered from dust in the companion body, or emission from young stars within the nebula- appears necessary to explain the observations. These observations may be indicative of the first stages in the assembly of galaxy-sized structures.Comment: 8 pages, 4 figures, plain LaTeX. Accepted for publication in Natur

Social network size, loneliness, physical functioning and depressive symptoms among older adults: Examining reciprocal associations in four waves of the Longitudinal Aging Study Amsterdam (LASA)

Previous research indicates that social isolation, loneliness, physical dysfunction and depressive symptoms are interrelated factors, little is known about the potential pathways among them. The aim of the study is to analyse simultaneously reciprocal relationships that could exist between the four factors to clarify potential mediation effects. METHODS Within a large representative sample of older people in the Longitudinal Aging Study Amsterdam (LASA), participants aged 75 and over were followed up over a period of 11 years (four waves). We tested cross-lagged and autoregressive longitudinal associations of social network size, loneliness, physical functioning and depressive symptoms using structural equation modelling (SEM). RESULTS Several statistically significant cross-lagged associations were found: decreasing physical functioning (Coef.=-0.03; p<0.05), as well as social network size (Coef.=-0.02; p<0.05), predicted higher levels of loneliness, which predicted an increase in depressive symptoms (Coef.=0.17; p<0.05) and further reduction of social network (Coef.=-0.20; p<0.05). Decreasing physical functioning also predicted an increase in depressive symptoms (Coef.=-0.08; p<0.05). All autoregressive associations were statistically significant. CONCLUSION Interventions focused on promoting social activities among older adults after negative life events, such as loss of social contacts or declining physical function, may alleviate feelings of loneliness and act as mental health protector

Selective serotonin reuptake inhibitors in the treatment of generalized anxiety disorder

Selective serotonin reuptake inhibitors have proven efficacy in the treatment of panic disorder, obsessive–compulsive disorder, post-traumatic stress disorder and social anxiety disorder. Accumulating data shows that selective serotonin reuptake inhibitor treatment can also be efficacious in patients with generalized anxiety disorder. This review summarizes the findings of randomized controlled trials of selective serotonin reuptake inhibitor treatment for generalized anxiety disorder, examines the strengths and weaknesses of other therapeutic approaches and considers potential new treatments for patients with this chronic and disabling anxiety disorder

Generating Computational Models for Serious Gaming

Westera, W. (2013, 25 October). Generating computational models for serious gaming. Presentation at the GALA Serious Gaming Conference, Paris, France.Many serious games include computational models that simulate dynamic systems. These models promote enhanced interaction and responsiveness. Under the social web paradigm more and more usable game authoring tools become available that enable prosumers to create their own games, but the inclusion of dynamic simulations remains a specialist’s job involving knowledge of mathematics, numerical modeling and programming. This presentation explains a methodology for specifying and running a specific subset of computational models without the need of bothering with mathematical equations. The methodology comprises a knowledge elicitation procedure for identifying and specifying the required model components, whereupon the mathematical model is automatically generated. The approach is based on the fact that many games focus on optimisation problems that are covered by a general class of linear programming models. The presentation thus sketches the principles of a creativity tool that removes barriers for harvesting the creative potential of teachers and students

Multiple dimensions of health locus of control in a representative population sample: ordinal factor analysis and cross-validation of an existing three and a new four factor model

<p>Abstract</p> <p>Background</p> <p>Based on the general approach of locus of control, health locus of control (HLOC) concerns control-beliefs due to illness, sickness and health. HLOC research results provide an improved understanding of health related behaviour and patients' compliance in medical care. HLOC research distinguishes between beliefs due to Internality, Externality powerful Others (POs) and Externality Chance. However, evidences for differentiating the POs dimension were found. Previous factor analyses used selected and predominantly clinical samples, while non-clinical studies are rare. The present study is the first analysis of the HLOC structure based on a large representative general population sample providing important information for non-clinical research and public health care.</p> <p>Methods</p> <p>The standardised German questionnaire which assesses HLOC was used in a representative adult general population sample for a region in Northern Germany (N = 4,075). Data analyses used ordinal factor analyses in LISREL and Mplus. Alternative theory-driven models with one to four latent variables were compared using confirmatory factor analysis. Fit indices, chi-square difference tests, residuals and factor loadings were considered for model comparison. Exploratory factor analysis was used for further model development. Results were cross-validated splitting the total sample randomly and using the cross-validation index.</p> <p>Results</p> <p>A model with four latent variables (Internality, Formal Help, Informal Help and Chance) best represented the HLOC construct (three-dimensional model: normed chi-square = 9.55; RMSEA = 0.066; CFI = 0.931; SRMR = 0.075; four-dimensional model: normed chi-square = 8.65; RMSEA = 0.062; CFI = 0.940; SRMR = 0.071; chi-square difference test: p < 0.001). After excluding one item, the superiority of the four- over the three-dimensional HLOC construct became very obvious (three-dimensional model: normed chi-square = 7.74; RMSEA = 0.059; CFI = 0.950; SRMR = 0.079; four-dimensional model: normed chi-square = 5.75; RMSEA = 0.049; CFI = 0.965; SRMR = 0.065; chi-square difference test: p < 0.001). Results were confirmed by cross-validation. Results based on our large community sample indicated that western general populations separate health-related control-beliefs concerning formal and informal assistance.</p> <p>Conclusions</p> <p>Future non-clinical HLOC studies in western cultures should consider four dimensions of HLOC: Internality, Formal Help, Informal Help and Chance. However, the standardised German instrument needs modification. Therefore, confirmation of our results may be useful. Future research should compare HLOC structure between clinical and non-clinical samples as well as cross-culturally.</p