Lipopolysaccharide modification in Gram-negative bacteria during chronic infection

The Gram-negative bacterial lipopolysaccharide (LPS) is a major component of the outer membrane that plays a key role in host-pathogen interactions with the innate immune system. During infection, bacteria are exposed to a host environment that is typically dominated by inflammatory cells and soluble factors, including antibiotics, which provide cues about regulation of gene expression. Bacterial adaptive changes including modulation of LPS synthesis and structure are a conserved theme in infections, irrespective of the type or bacteria or the site of infection. In general, these changes result in immune system evasion, persisting inflammation, and increased antimicrobial resistance. Here, we review the modifications of LPS structure and biosynthetic pathways that occur upon adaptation of model opportunistic pathogens (Pseudomonas aeruginosa, Burkholderia cepacia complex bacteria, Helicobacter pylori and Salmonella enterica) to chronic infection in respiratory and gastrointestinal sites. We also discuss the molecular mechanisms of these variations and their role in the host-pathogen interaction.

The Legitimacy of Subsidiary Issue Selling: Balancing Positive & Negative Attention from Corporate Headquarters

We consider how in issue selling, subsidiaries draw on different forms of legitimacy to attract corporate headquarters’ (CHQ) positive attention and minimise negative CHQ attention. Through case study evidence, we find that directing CHQ attention to subsidiary issues needs to be executed as a balancing act through forms of subsidiary legitimacy, namely; the personal legitimacy of key individuals at the subsidiary; consequential legitimacy vis-à-vis peer subsidiaries; and linkage legitimacy in the local environment. We develop a typology of subsidiary issue-selling roles and illustrate how negative CHQ attention results from a failure to legitimise issue selling.

Vibrational excitation of the N2+ first negative (0,0), (1,0) and (2,0) bands by electron impact: a theoretical study using the R-matrix approach

Ab initio cross section calculations for vibronic excitation using the R -matrix approach have been performed on the N 2 + molecular ion complex. A three-state close-coupling expansion is used where the electronic target states; X 2 g + , A 2 u and B 2 u + of the molecular cation are represented by a valence configuration-interaction approximation. A non-adiabatic approximation is invoked to study vibronic excitation for the first three negative bands, (0,0), (1,0) and (2,0) of the X-B transition (B 2 u + v ´ X 2 g + v ´´ ) of N 2 + . Fixed-nuclei and non-adiabatic cross section results are compared with the available experimental data for the (0,0) band and the breakdown of the adiabatic fixed-nuclei approximation is clearly evident for the vibronic excitation of the (1,0) and (2,0) bands in this molecular ion complex.

Capture and loss of electron by MeV ions penetrating through liquid spray:Formation of negative ion and neutral atom beams

Charge changing processes of MeV ions penetrating through liquid spray is confirmed to be abundant source of various energetic negative ion and neutral atom beams its generic nature is demonstrated.

The value of adjuvant radiotherapy on survival and recurrence in triple-negative breast cancer: a systematic review and meta-analysis of 5,507 patients

BACKGROUND: The value of adjuvant radiotherapy in triple negative breast cancer (TNBC) remains unclear. A systematic review and meta-analysis was conducted in TNBC patients to assess survival and recurrence outcomes associated with radiotherapy following either breast conserving therapy (BCT) or post-mastectomy radiotherapy (PMRT). METHODS: Four electronic databases were searched from January 2000 to November 2015 (PubMed, MEDLINE, EMBASE and Web of Science). Studies investigating overall survival and/or recurrence in TNBC patients according to radiotherapy administration were included. A random effects meta-analysis was conducted using mastectomy only patients as the reference.  RESULTS: Twelve studies were included. The pooled hazard ratio (HR) for locoregional recurrence comparing BCT and PMRT to mastectomy only was 0.61 (95% confidence interval [CI] 0.41-0.90) and 0.62 (95% CI 0.44-0.86), respectively. Adjuvant radiotherapy was not significantly associated with distant recurrence. The pooled HR for overall survival comparing BCT and PMRT to mastectomy only was 0.57 (95% CI 0.36-0.88) and HR 1.12 (95% CI 0.75, 1.69). Comparing PMRT to mastectomy only, tests for interaction were not significant for stage (p=0.98) or age at diagnosis (p=0.85). However, overall survival was improved in patients with late-stage disease (T3-4, N2-3) pooled HR 0.53 (95% CI 0.32-0.86), and women <40 years, pooled HR 0.30 (95% CI 0.11-0.82). CONCLUSIONS: Adjuvant radiotherapy was associated with a significantly lower risk of locoregional recurrence in TNBC patients, irrespective of the type of surgery. While radiotherapy was not consistently associated with an overall survival gain, benefits may be obtained in women with late-stage disease and younger patients. 

Potential strategies for the eradication of multi-drug resistant Gram-negative bacterial infections

Antimicrobial resistance is one of the leading threats to society. The increasing burden of multidrug-resistant Gram-negative infection is particularly concerning as such bacteria are demonstrating resistance to nearly all currently licensed therapies. Various strategies have been hypothesized to treat multidrug-resistant Gram-negative infections including: targeting the Gram-negative outer membrane; neutralization of lipopolysaccharide; inhibition of bacterial efflux pumps and prevention of protein folding. Silver and silver nanoparticles, fusogenic liposomes and nanotubes are potential strategies for extending the activity of licensed, Gram-positive selective, antibiotics to Gram-negatives. This may serve as a strategy to fill the current void in pharmaceutical development in the short term. This review outlines the most promising strategies that could be implemented to solve the threat of multidrug-resistant Gram-negative infections

Perceived positive and negative consequences after surviving cancer and their relation to quality of life

Surviving childhood cancer has multiple implications on both physical and psychological domains of the individual. However, its study and possible effects on health-related quality of life (HRQoL) outcomes of adolescent survivors has been understudied. The objective of this study was twofold; to assess positive and negative cancer-related consequences (psychosocial and physical) in a sample of adolescent cancer survivors and to explore their relationship with HRQoL outcomes. Forty-one participants answered two questions about positive and negative consequences in the aftermath of cancer and filled in the KIDSCREEN-52 self-reported version. Data were analysed using mixed methods approach. 87.8% of the sample identified positive consequences and 63.4% negative consequences in survivorship. Four positive categories and five negative categories with regard to cancer-related consequences were found. Changed perspectives in life narratives seem to be the positive consequence more related to HRQoL (physical well-being, mood & emotions, autonomy, social support & peers), followed by useful life experience (physical well-being, autonomy, social support & peers). Psychological impact was the most referred negative consequence with a significant detrimental effect on social support and peers HRQoL dimension. Even if the majority of survivors reported benefit finding in the aftermath of cancer, concomitant positive and negative consequences have been found. However, findings only reveal a significant relationship between positive narratives and HRQoL, and negative consequences do not seem to have a significant influence on overall HRQoL in survivorship.

Identification of Streptococcus gallolyticus subsp. macedonicus as the etiological agent in a case of culture-negative multivalve infective endocarditis by 16S rDNA PCR analysis of resected valvular tissue

Today, PCR using broad-range primers is being used increasingly to detect pathogens from resected heart valves. Herein is described the first case of multivalve infective endocarditis where 16S rDNA PCR was used to detect a single pathogen from two affected valves in a 61-year-old man. Triple heart valve replacement was required despite six weeks of appropriate antimicrobial therapy. The organism was confirmed as Streptococcus gallolyticus subsp. macedonicus, a member of the 'S. equinus/S. bovis' complex. To date, only one report has been made of human infection due to this organism. This may be due to the limited resolution of the routine diagnostic methods used and/or as a consequence of the complex nomenclature associated with this group of organisms.

Colour Sensation and Empathy: Arthur Schopenhauer's Negative Philosophy and Colour Theory as the Basis of an Elemental Colour Architecture

Arthur Schopenhauer proposed a theory of colour as a consequence of his first hand knowledge of J.W. Goethe’s experiments with color phenomena. This colour theory can be used to explore an interesting proposition Schopenhauer made about architecture. For Schopenhauer, architecture is about feelings, not about functions or forms, its purpose as an art is to reveal the principles of primitive forces, specifically gravity and rigidity. For Schopenhauer, architecture expresses these forces in the poised equilibrium of massive structures built out of stone. Schopenhauer was inclined to believed that architecture had already achieved its most perfect expression in Greek temple architecture. However; he did offer one possibility for architectural research: this was the suggestion that architecture was also concerned with the expression of light. It seems never to have occurred to Schopenhauer to use his colour theory to speculate about light in architecture. This paper explores some of the implications of Schopenhauer’s theory of colour for his aesthetics of architecture?

ß-lactamases in the biochemistry and molecular biology laboratory

β-lactamases are hydrolytic enzymes that inactivate the β-lactam ring of antibiotics such as penicillins and cephalosporins. The major diversity of studies carried out until now have mainly focused on the characterization of β-lactamases recovered among clinical isolates of Gram-positive staphylococci and Gram-negative enterobacteria, amongst others. However, only some studies refer to the detection and development of β-lactamases carriers in healthy humans, sick animals, or even in strains isolated from environmental stocks such as food, water, or soils. Considering this, we proposed a 10-week laboratory programme for the Biochemistry and Molecular Biology laboratory for majors in the health, environmental, and agronomical sciences. During those weeks, students would be dealing with some basic techniques such as DNA extraction, bacterial transformation, polymerase chain reaction (PCR), gel electrophoresis, and the use of several bioinformatics tools. These laboratory exercises would be conducted as a mini research project in which all the classes would be connected with the previous ones. This curriculum was compared in an experiment involving two groups of students from two different majors. The new curriculum, with classes linked together as a mini research project, was taught to a major in Pharmacy and an old curriculum was taught to students from environmental health. The results showed that students who were enrolled in the new curriculum obtained better results in the final exam than the students who were enrolled in the former curriculum. Likewise, these students were found to be more enthusiastic during the laboratory classes than those from the former curriculum.