A rhlI 5′ UTR-Derived sRNA Regulates RhlR-Dependent Quorum Sensing in Pseudomonas aeruginosa

N-Acyl homoserine lactone (AHL) quorum sensing (QS) controls expression of over 200 genes in Pseudomonas aeruginosa. There are two AHL regulatory systems: the LasR-LasI circuit and the RhlR-RhlI system. We mapped transcription termination sites affected by AHL QS in P. aeruginosa, and in doing so we identified AHL-regulated small RNAs (sRNAs). Of interest, we noted that one particular sRNA was located within the rhlI locus. We found that rhlI, which encodes the enzyme that produces the AHL N-butanoyl-homoserine lactone (C4-HSL), is controlled by a 5′ untranslated region (UTR)-derived sRNA we name RhlS. We also identified an antisense RNA encoded opposite the beginning of the rhlI open reading frame, which we name asRhlS. RhlS accumulates as wild-type cells enter stationary phase and is required for the production of normal levels of C4-HSL through activation of rhlI translation. RhlS also directly posttranscriptionally regulates at least one other unlinked gene, fpvA. The asRhlS appears to be expressed at maximal levels during logarithmic growth, and we suggest RhlS may act antagonistically to the asRhlS to regulate rhlI translation. The rhlI-encoded sRNAs represent a novel aspect of RNA-mediated tuning of P. aeruginosa QS

Protein cross-linking by chlorinated polyamines and transglutamylation stabilizes neutrophil extracellular traps.

Neutrophil extracellular trap (NET) ejected from activated dying neutrophils is a highly ordered structure of DNA and selected proteins capable to eliminate pathogenic microorganisms. Biochemical determinants of the non-randomly formed stable NETs have not been revealed so far. Studying the formation of human NETs we have observed that polyamines were incorporated into the NET. Inhibition of myeloperoxidase, which is essential for NET formation and can generate reactive chlorinated polyamines through hypochlorous acid, decreased polyamine incorporation. Addition of exogenous primary amines that similarly to polyamines inhibit reactions catalyzed by the protein cross-linker transglutaminases (TGases) has similar effect. Proteomic analysis of the highly reproducible pattern of NET components revealed cross-linking of NET proteins through chlorinated polyamines and varepsilon(gamma-glutamyl)lysine as well as bis-gamma-glutamyl polyamine bonds catalyzed by the TGases detected in neutrophils. Competitive inhibition of protein cross-linking by monoamines disturbed the cross-linking pattern of NET proteins, which resulted in the loss of the ordered structure of the NET and significantly reduced capacity to trap bacteria. Our findings provide explanation of how NETs are formed in a reproducible and ordered manner to efficiently neutralize microorganisms at the first defense line of the innate immune system

Towards energy aware cloud computing application construction

The energy consumption of cloud computing continues to be an area of significant concern as data center growth continues to increase. This paper reports on an energy efficient interoperable cloud architecture realised as a cloud toolbox that focuses on reducing the energy consumption of cloud applications holistically across all deployment models. The architecture supports energy efficiency at service construction, deployment and operation. We discuss our practical experience during implementation of an architectural component, the Virtual Machine Image Constructor (VMIC), required to facilitate construction of energy aware cloud applications. We carry out a performance evaluation of the component on a cloud testbed. The results show the performance of Virtual Machine construction, primarily limited by available I/O, to be adequate for agile, energy aware software development. We conclude that the implementation of the VMIC is feasible, incurs minimal performance overhead comparatively to the time taken by other aspects of the cloud application construction life-cycle, and make recommendations on enhancing its performance

The influence of the cultural climate of the training environment on physicians' self-perception of competence and preparedness for practice

<p>Abstract</p> <p>Background</p> <p>In current supervisory practice, the learning environment in which the training of specialist registrars (SpRs) takes place is important. Examples of such learning environments are the hospital settings and/or geographical locations where training occurs. Our objective was to investigate whether the cultural climate of different learning environments influences physicians' perceived level of competence and preparedness for practice.</p> <p>Methods</p> <p>An electronic questionnaire was sent to an equal group of paediatricians who had trained in clinical settings located in Europe and the Caribbean. 30 items (Likert scale 1–4 = totally disagree-totally agree) were used to measure the level of preparedness of the respondents in 7 physician competencies.</p> <p>Results</p> <p>42 participants were included for analysis. The distribution of participants in both groups was comparable. The overall perception of preparedness in the Caribbean group was 2.93 (SD = 0.47) and 2.86 (SD = 0.72) in the European group. The European group felt less prepared in the competency as manager 1.81 (SD = 1.06) compared to their Caribbean counterparts 2.72 (SD = 0.66). The difference was significant (p = 0.006).</p> <p>Conclusion</p> <p>The training in the different environments was perceived as adequate and comparable in effect. The learning environment's cultural climate appeared to influence the physician's perception of their competencies and preparedness for clinical practice.</p

Not Just Efficiency: Insolvency Law in the EU and Its Political Dimension

Certain insolvency law rules, like creditors’ priorities and set-off rights, have a distributive impact on creditors. Distributional rules reflect the hierarchies of values and interests in each jurisdiction and, as a result, have high political relevance and pose an obstacle to reforming the EU Insolvency Regulation. This paper will show the difficulty of reform by addressing two alternative options to regulate cross-border insolvencies in the European Union. The first one is the ‘choice model’, under which companies can select the insolvency law they prefer. Although such a model would allow distressed firms to select the most efficient insolvency law, it would also displace Member States’ power to protect local constituencies. The choice model therefore produces negative externalities and raises legitimacy concerns. The opposite solution is full harmonisation of insolvency law at EU level, including distributional rules. Full harmonisation would have the advantage of internalising all externalities produced by cross-border insolvencies. However, the EU legislative process, which is still based on negotiations between states, is not apt to decide on distributive insolvency rules; additionally, if harmonisation includes such rules, it will indirectly modify national social security strategies and equilibria. This debate shows that the choice regarding power allocation over bankruptcies in the EU depends on the progress of European integration and is mainly a matter of political legitimacy, not only of efficiency

A rhlI 5′ UTR-Derived sRNA Regulates RhlR-Dependent Quorum Sensing in Pseudomonas aeruginosa

N-Acyl homoserine lactone (AHL) quorum sensing (QS) controls expression of over 200 genes in Pseudomonas aeruginosa. There are two AHL regulatory systems: the LasR-LasI circuit and the RhlR-RhlI system. We mapped transcription termination sites affected by AHL QS in P. aeruginosa, and in doing so we identified AHL-regulated small RNAs (sRNAs). Of interest, we noted that one particular sRNA was located within the rhlI locus. We found that rhlI, which encodes the enzyme that produces the AHL N-butanoyl-homoserine lactone (C4-HSL), is controlled by a 5′ untranslated region (UTR)-derived sRNA we name RhlS. We also identified an antisense RNA encoded opposite the beginning of the rhlI open reading frame, which we name asRhlS. RhlS accumulates as wild-type cells enter stationary phase and is required for the production of normal levels of C4-HSL through activation of rhlI translation. RhlS also directly posttranscriptionally regulates at least one other unlinked gene, fpvA. The asRhlS appears to be expressed at maximal levels during logarithmic growth, and we suggest RhlS may act antagonistically to the asRhlS to regulate rhlI translation. The rhlI-encoded sRNAs represent a novel aspect of RNA-mediated tuning of P. aeruginosa QS

Educating the public health workforce: Issues and challenges

Background: In public health, as well as other health education contexts, there is increasing recognition of the transformation in public health practice and the necessity for educational providers to keep pace. Traditionally, public health education has been at the postgraduate level; however, over the past decade an upsurge in the growth of undergraduate public health degrees has taken place. Discussion: This article explores the impact of these changes on the traditional sphere of Master of Public Health programs, the range of competencies required at undergraduate and postgraduate levels, and the relevance of these changes to the public health workforce. It raises questions about the complexity of educational issues facing tertiary institutions and discusses the implications of these issues on undergraduate and postgraduate programs in public health. Conclusion: The planning and provisioning of education in public health must differentiate between the requirements of undergraduate and postgraduate students – while also addressing the changing needs of the health workforce. Within Australia, although significant research has been undertaken regarding the competencies required by postgraduate public health students, the approach is still somewhat piecemeal, and does not address undergraduate public health. This paper argues for a consistent approach to competencies that describe and differentiate entry-level and advanced practice

Long-term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply

Transplantation of encapsulated islets can cure diabetes without immunosuppression, but oxygen supply limitations can cause failure. We investigated a retrievable macroencapsulation device wherein islets are encapsulated in a planar alginate slab and supplied with exogenous oxygen from a replenishable gas chamber. Translation to clinically-useful devices entails reduction of device size by increasing islet surface density, which requires increased gas chamber pO Here we show that islet surface density can be substantially increased safely by increasing gas chamber pO to a supraphysiological level that maintains all islets viable and functional. These levels were determined from measurements of pO profiles in islet-alginate slabs. Encapsulated islets implanted with surface density as high as 4,800 islet equivalents/cm in diabetic rats maintained normoglycemia for more than 7 months and provided near-normal intravenous glucose tolerance tests. Nearly 90% of the original viable tissue was recovered after device explantation. Damaged islets failed after progressively shorter times. The required values of gas chamber pO were predictable from a mathematical model of oxygen consumption and diffusion in the device. These results demonstrate feasibility of developing retrievable macroencapsulated devices small enough for clinical use and provide a firm basis for design of devices for testing in large animals and humans

Nutrition in Pediatric Inflammatory Bowel Disease: A Position Paper on Behalf of the Porto Inflammatory Bowel Disease Group of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition

Background and Aims:A growing body of evidence supports the need for detailed attention to nutrition and diet in children with inflammatory bowel disease (IBD). We aimed to define the steps in instituting dietary or nutritional management in light of the current evidence and to offer a useful and practical guide to physicians and dieticians involved in the care of pediatric IBD patients.Methods:A group of 20 experts in pediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to Nutrition Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition Porto, IBD Interest, and Nutrition Committee. A list of 41 predefined questions was addressed by working subgroups based on a systematic review of the literature.Results:A total of 53 formal recommendations and 47 practice points were endorsed with a consensus rate of at least 80% on the following topics: nutritional assessment;macronutrients needs;trace elements, minerals, and vitamins;nutrition as a primary therapy of pediatric IBD;probiotics and prebiotics;specific dietary restrictions;and dietary compounds and the risk of IBD.Conclusions:This position paper represents a useful guide to help the clinicians in the management of nutrition issues in children with IBD

Generalizability of nociception level as a measure of intraoperative nociceptive stimulation: a retrospective analysis

BackgroundNociception-guided intraoperative opioid administration might help reduce postoperative pain. A commonly used and validated nociception monitor system is nociception level (NOL), which provides the nociception index, ranging from 0 to 100, with 0 representing no nociception and 100 representing extreme nociception. We tested the hypothesis that NOL responses are similar in men and women given remifentanil and fentanyl, across various types of anesthesia, as a function of American Society of Anesthesiologists physical status designations, and over a range of ages and body morphologies.MethodsWe conducted a retrospective cohort analysis of trial data from eight prospective NOL validation studies. Among 522 noncardiac surgical patients enrolled in these studies, 447 were included in our analysis. We assessed NOL responses to various noxious and non-noxious stimuli.ResultsThe average NOL in response to 315 noxious stimuli was 47 ± 15 (95% CI = 45–49). The average NOL in response to 361 non-noxious stimuli was 10 ± 12 (95% CI = 9–11). NOL responses were similar in men and women, in patients given remifentanil and fentanyl, across various types of anesthesia, as a function of American Society of Anesthesiologists physical status designations, and over a range of ages and body morphologies.ConclusionNociception level appears to provide accurate estimates of intraoperative nociception over a broad range of patients and anesthetic conditions.Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care