The effect of montelukast on exhaled nitric oxide of alveolar and bronchial origin in inhaled corticosteroid-treated asthma

SummaryBackgroundInhaled corticosteroid therapy suppresses nitric oxide levels (NO) of airway origin but not necessarily NO of alveolar or small airway origin. Systemic therapy with an oral anti-leukotriene agent may suppress NO production in distal airways and alveoli not reached by inhaled therapy.MethodsAdult patients with mild asthma were treated for 3 weeks with inhaled fluticasone 250μg twice daily then with inhaled fluticasone plus oral montelukast 10mg daily for 3 additional weeks. We monitored exhaled NO (eNO), spirometry, lung volumes, and asthma symptoms scores at baseline and at the end of each treatment period. In a subset of patients, we continued with montelukast monotherapy and repeated these measurements.ResultsIn the 18 patients studied, pulmonary function parameters and asthma symptom scores were not altered significantly from baseline by any therapy. The total eNO at baseline was 55±35.3ppb, dropping to 28.1±15.3ppb (p=0.005) after 3 weeks of fluticasone and to 23.5±14ppb (p=0.001 vs. baseline) after the addition of montelukast. The trend towards reduced total eNO with the combination therapy vs. monotherapy was not statistically significant. Alveolar eNO dropped from 4.2±2.4 at baseline to 3.0±1.5 (p=0.1) after fluticasone and then to 2.2±0.9 (p=0.08 vs. baseline) after fluticasone plus montelukast, increasing then to 3.8±1.8 after montelukast alone (p=0.6 vs. baseline).ConclusionsLeukotriene receptor antagonists administered systemically might decrease small airway/alveolar sites of inflammation when combined to inhaled corticosteroid therapy

Vector valued chebechev systems

Let I be the unit interval and X be a real Banach space. The space of continuous functions on I with values in X is denoted by C(I,X). The object of this paper is to introduce Chebechev systems in C(I,X) and study the basi.c properties of such systems, and its relation to interpolation. It is also proved that a subspace that is generated by a weak Chebechev  system in C(I,X) is a Chebechev subspace

Metabolomic Heterogeneity of Pulmonary Arterial Hypertension

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Additional roles of a peripheral loop–loop interaction in the Neurospora VS ribozyme

Many RNAs contain tertiary interactions that contribute to folding the RNA into its functional 3D structure. In the VS ribozyme, a tertiary loop–loop kissing interaction involving stem–loops I and V is also required to rearrange the secondary structure of stem–loop I such that nucleotides at the base of stem I, which contains the cleavage–ligation site, can adopt the conformation required for activity. In the current work, we have used mutants that constitutively adopt the catalytically permissive conformation to search for additional roles of the kissing interaction in vitro. Using mutations that disrupt or restore the kissing interaction, we find that the kissing interaction contributes ∼1000-fold enhancement to the rates of cleavage and ligation. Large Mg2+-dependent effects on equilibrium were also observed: in the presence of the kissing interaction cleavage is favored >10-fold at micromolar concentrations of Mg2+; whereas ligation is favored >10-fold at millimolar concentrations of Mg2+. In the absence of the kissing interaction cleavage exceeds ligation at all concentrations of Mg2+. These data provide evidence that the kissing interaction strongly affects the observed cleavage and ligation rate constants and the cleavage–ligation equilibrium of the ribozyme

Processfolio: uniting Academic Literacies and Critical Emancipatory Action Research for practitioner-led inquiry into EAP writing assessment

This paper reports on the design and implementation of an alternative form of writing assessment on a UK English for Academic Purposes (EAP) presessional course. The assessment, termed processfolio, was a response to research inquiry into how writing assessment in a local context negated student agency and inculcated disempowering models of teaching and learning academic writing. The project merged an Academic Literacies approach to writing (Lea and Street, 1998) with a Critical Emancipatory Action Research (Carr and Kemmis, 1986) framework and a Critical Realist(Bhaskar, 1989) perspective. Data collected from the folios and interviews with students and teachers on their experiences of the processfolio found that a small scale intervention has potential for agency to be exercised within the highly constrained context of a UK EAP pre-sessional. New directions in research are proposed which can engage students and teachers to work for change in UK EAP assessment within their internal and external constraints

WriteSim TCExam - An open source text simulation environment for training novice researchers in scientific writing

BACKGROUND: The ability to write clearly and effectively is of central importance to the scientific enterprise. Encouraged by the success of simulation environments in other biomedical sciences, we developed WriteSim TCExam, an open-source, Web-based, textual simulation environment for teaching effective writing techniques to novice researchers. We shortlisted and modified an existing open source application - TCExam to serve as a textual simulation environment. After testing usability internally in our team, we conducted formal field usability studies with novice researchers. These were followed by formal surveys with researchers fitting the role of administrators and users (novice researchers) RESULTS: The development process was guided by feedback from usability tests within our research team. Online surveys and formal studies, involving members of the Research on Research group and selected novice researchers, show that the application is user-friendly. Additionally it has been used to train 25 novice researchers in scientific writing to date and has generated encouraging results. CONCLUSION: WriteSim TCExam is the first Web-based, open-source textual simulation environment designed to complement traditional scientific writing instruction. While initial reviews by students and educators have been positive, a formal study is needed to measure its benefits in comparison to standard instructional methods

The reign of the Caliph al-Wathig (842-847 A.D.) according to al-Tabari’s history: an annotated translation

This thesis concerns the Reign of al-Wathiq, the ninth ‘Abbasid caliph (227-232/842-847), a time considered the seal of the Golden Period of the ‘Abbasid Caliphate. The thesis comprises a translation into English of the account of al-Tabarï on the reign of al-Wâthiq which has not previously been translated into any other language. The Annotations give an explanation of the important events, terms and personalities mentioned in the text, and correct some information related to certain events. The Introduction gives portraits of al-Wâthiq as viewed by other historians; the Conclusion gives a brief comment on and evaluation of the caliph in his military and civil activities

Variation at DENND1B and Asthma on the Island of Tristan da Cunha

A high prevalence of asthma has been documented among the inhabitants of Tristan da Cunha, an isolated island in the South Atlantic. The population derives from just 28 founders. We performed lung function testing, including methacholine inhalation challenge, allergen skin prick testing, and collected DNA from essentially all of the current island population (269 individuals), and genotyped a panel of 43 single-nucleotide polymorphisms (SNPs) reported as associated with asthma and atopy. We carried out a mixed-model association analysis using the known pedigree. There were 96 individuals diagnosed as asthmatic (36%), and heritability estimates were similar to those from nonisolated population samples (multifactorial threshold model, h2 = 48%). The first component from a genetic principal components analysis using the entire SNP panel was nonlinearly associated with asthma, with the maximum risk to those intermediate to reference (Human Genome Diversity Project) European and African samples means. The single most strongly associated SNP was rs2786098 (p = 5.5 × 10-5), known to regulate the gene DENND1B. This explained approximately one-third of the trait heritability, with an allelic odds ratio for the A allele of 2.6. Among A/A carriers, 10 out of 12 individuals were asthmatic. The rs2786098*A variant was initially reported to decrease the risk of childhood (atopic) asthma in European but slightly increase the risk in African-descended populations, and does significantly alter Th2 cell function. Despite an absence of overall association with this variant in recent asthma genome wide association studies meta-analyses, an effect may exist on the particular genetic background of the Tristan da Cunha population