Perceptions of asthma and exercise in adolescents with and without asthma

Objective: To elicit the views of adolescents, with and without asthma, about exercise and asthma, and the perceived benefits of and barriers to participation. The adolescent views elicited would subsequently inform the design of a high-intensity exercise intervention to improve asthma control. Methods: Fifty-four adolescents (age 13.1±0.9years; 26 with asthma) participated in twelve semi-structured group interviews. Questions were structured around knowledge, attitudes and beliefs towards asthma and its impact on exercise participation and lifestyle. The interviews were transcribed verbatim, thematically analysed and presented via diagrams of emergent themes. Ethical approval was granted by the institutional research ethics committee. Results: Fear of an asthma attack emerged as the main barrier to exercise, with many adolescents with asthma withdrawing from exercise as a coping strategy; many healthy adolescents perceived this withdrawal as laziness or an excuse. Despite this, the majority (81%) of adolescents with asthma reported exercise to be their most enjoyable activity. Adolescents suggested incorporating mixed activities, such as team games (e.g., rounders, football, netball), for future interventions to ensure adherence. Conclusions: Whilst exercise is important in the management of asthma, the tendency of those with asthma to withdraw from exercise to avoid adverse events could be addressed through a games-based high-intensity exercise intervention. Furthermore, educating all adolescents on asthma could simultaneously reduce stigmatisation and enhance exercise engagement

The Prevalence of Previously Undiagnosed Leprosy in the General Population of Northwest Bangladesh

In order to estimate the level of leprosy in an area with many leprosy patients, we determined the prevalence of previously undiagnosed leprosy in the general population and compared this with the registered (or known) number of leprosy patients. We also compared it with the known prevalence of leprosy in contacts of leprosy patients. We examined 20 randomly selected geographical clusters of 1,000 persons each in two districts of Bangladesh, with over 4 million population. Physical examination was performed on all individuals. The number of newly found leprosy cases among 17,862 people above 5 years of age from the clusters was 27, giving a rate of previously undiagnosed leprosy of 15.1 per 10,000. This rate is six times higher than the registered prevalence, but three times lower than the rate in the most distant subgroup of contacts (neighbour of neighbour and social contacts) of leprosy patients in the same area. We conclude that in areas where leprosy is common, it may be preferable to do full village or neighbourhood surveys when a new leprosy patient is found, rather than to limit contact surveys to close contacts only, such as household members

Mucin structural interactions with an alginate oligomer mucolytic in cystic fibrosis sputum

Cystic fibrosis (CF) is an autosomal recessive, life-limiting condition characterized by progressive lung disease, which is a major cause of morbidity and mortality for these patients. The inhalation therapy, OligoG CF-5/20, is a low molecular weight (mean Mn 3200 g/mol) alginate oligomer, with a high guluronic acid content (>85%). The ability of OligoG CF-5/20 to enhance the activity of antimicrobial/antibiotic therapies, modify the rheological properties of CF sputum and interact with mucin, has previously been shown. To further characterize the physicochemical interactions of OligoG CF-5/20 with CF sputum, Fourier-transform infrared (FTIR) spectroscopy was used to analyze ex vivo sputum samples from adolescent CF patients (n = 13) following treatment with 0.2% OligoG CF-5/20. FTIR analysis confirmed the interaction of OligoG CF-5/20 with mucin glycans in CF sputum, which showed a shift in wavenumber from 1078 cm−1 to 1070 cm-1 and subsequent loss of the 1053 cm−1 peak in the OligoG CF-5/20 treated samples. OligoG CF-5/20 interaction with key terminal moieties in mucin were also evident, with a significant change in sulphation at wavenumber 1116 cm−1, suggesting a link with sulphated Lewis x antigen. There were also significant shifts at wavenumber 1637 cm-1 indicative of β-sheet conformational changes in the mucin peptide caused by action of OligoG. The alterations in charge of glycan and mucin structures support previous observations wherein OligoG CF-5/20 modifies the viscoelastic properties of CF sputum. These findings suggest a possible mechanism of action for the rheological changes observed with this novel therapy

A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease

The host- and bacteria-derived extracellular polysaccharide coating of the lung is a considerable challenge in chronic respiratory disease and is a powerful barrier to effective drug delivery. A low molecular weight 12–15-mer alginate oligosaccharide (OligoG CF-5/20), derived from plant biopolymers, was shown to modulate the polyanionic components of this coating. Molecular modeling and Fourier transform infrared spectroscopy demonstrated binding between OligoG CF-5/20 and respiratory mucins. Ex vivo studies showed binding induced alterations in mucin surface charge and porosity of the three-dimensional mucin networks in cystic fibrosis (CF) sputum. Studies in Humans showed that OligoG CF-5/20 is safe for inhalation in CF patients with effective lung deposition and modifies the viscoelasticity of CF-sputum. OligoG CF-5/20 is the first inhaled polymer therapy, represents a novel mechanism of action and therapeutic approach for the treatment of chronic respiratory disease, and is currently in Phase IIb clinical trials for the treatment of CF

Early observations of the nearby type Ia supernova SN 2015F

We present photometry and time-series spectroscopy of the nearby type Ia supernova (SN Ia) SN 2015F over $-16$ days to $+80$ days relative to maximum light, obtained as part of the Public ESO Spectroscopic Survey of Transient Objects (PESSTO). SN 2015F is a slightly sub-luminous SN Ia with a decline rate of $\Delta m15(B)=1.35 \pm 0.03$ mag, placing it in the region between normal and SN 1991bg-like events. Our densely-sampled photometric data place tight constraints on the epoch of first light and form of the early-time light curve. The spectra exhibit photospheric C II $\lambda 6580$ absorption until $-4$ days, and high-velocity Ca II is particularly strong at $14000$ km s$^{-1}$, suggesting mixing in the outermost layers of the SN ejecta. Although unusual in SN Ia spectra, including V II in the modelling significantly improves the spectral fits. Intriguingly, we detect an absorption feature at $\sim$6800 \AA\ that persists until maximum light. Our favoured explanation for this line is photospheric Al II, which has never been claimed before in SNe Ia, although detached high-velocity C II material could also be responsible. In both cases the absorbing material seems to be confined to a relatively narrow region in velocity space. The nucleosynthesis of detectable amounts of Al II would argue against a low-metallicity white dwarf progenitor. We also show that this 6800 \AA\ feature is weakly present in other normal SN Ia events, and common in the SN 1991bg-like sub-class

Molecular analysis using DHPLC of cystic fibrosis: increase of the mutation detection rate among the affected population in Central Italy

BACKGROUND: Cystic fibrosis (CF) is a multisystem disorder characterised by mutations of the CFTR gene, which encodes for an important component in the coordination of electrolyte movement across of epithelial cell membranes. Symptoms are pulmonary disease, pancreatic exocrine insufficiency, male infertility and elevated sweat concentrations. The CFTR gene has numerous mutations (>1000) and functionally important polymorphisms (>200). Early identification is important to provide appropriate therapeutic interventions, prognostic and genetic counselling and to ensure access to specialised medical services. However, molecular diagnosis by direct mutation screening has proved difficult in certain ethnic groups due to allelic heterogeneity and variable frequency of causative mutations. METHODS: We applied a gene scanning approach using DHPLC system for analysing specifically all CFTR exons and characterise sequence variations in a subgroup of CF Italian patients from the Lazio region (Central Italy) characterised by an extensive allelic heterogeneity. RESULTS: We have identified a total of 36 different mutations representing 88% of the CF chromosomes. Among these are two novel CFTR mutations, including one missense (H199R) and one microdeletion (4167delCTAAGCC). CONCLUSION: Using this approach, we were able to increase our standard power rate of mutation detection of about 11% (77% vs. 88%)

Saccharothrix sp. PAL54, a new chloramphenicol-producing strain isolated from a Saharan soil

An actinomycete strain designated PAL54, producing an antibacterial substance, was isolated from a Saharan soil in Ghardaïa, Algeria. Morphological and chemical studies indicated that this strain belonged to the genus Saccharothrix. Analysis of the 16S rDNA sequence showed a similarity level ranging between 96.9 and 99.2% within Saccharothrix species, with S. longispora DSM 43749T, the most closely related. DNA–DNA hybridization confirmed that strain PAL54 belonged to Saccharothrix longispora. It showed very strong activity against pathogenic Gram-positive and Gram-negative bacteria responsible for nosocomial infections and resistant to multiple antibiotics. Strain PAL54 secreted the antibiotic optimally during mid-stationary and decline phases of growth. One antibacterial compound was isolated from the culture broth and purified by HPLC. The active compound was elucidated by uv-visible and NMR spectroscopy and by mass spectrometry. The results showed that this compound was a D(-)-threo chloramphenicol. This is the first report of chloramphenicol production by a Saccharothrix species

Michael Gove’s war on professional historical expertise : conservative curriculum reform, extreme Whig history and the place of imperial heroes in modern multicultural Britain

Six years of continuously baiting his opponents within the history profession eventually amounted to little where it mattered most. UK Secretary of State for Education, Michael Gove, finally backtracked in 2013 on his plans to impose a curriculum for English schools based on a linear chronology of the achievements of British national heroes. His ‘history as celebration’ curriculum was designed to instil pride amongst students in a supposedly shared national past, but would merely have accentuated how many students in modern multicultural Britain fail to recognise themselves in what is taught in school history lessons. Now that the dust has settled on Gove’s tenure as Secretary of State, the time is right for retrospective analysis of how his plans for the history curriculum made it quite so far. How did he construct an ‘ideological’ conception of expertise which allowed him to go toe-to-toe for so long with the ‘professional’ expertise of academic historians and history teachers? What does the content of this ideological expertise tell us about the politics of race within Conservative Party curriculum reforms? This article answers these questions to characterise Gove as a ‘whig historian’ of a wilfully extreme nature in his attachment to imperial heroes as the best way to teach national history in modern multicultural Britain

Assessment of p.Phe508del-CFTR functional restoration in pediatric primary cystic fibrosis airway epithelial cells

© 2018 Sutanto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Mutations in the cystic fibrosis transmembrane regulator (CFTR) gene can reduce function of the CFTR ion channel activity and impair cellular chloride secretion. The gold standard method to assess CFTR function of ion transport using the Ussing chamber requires a high number of airway epithelial cells grown at air-liquid interface, limiting the application of this method for high throughput screening of potential therapeutic compounds in primary airway epithelial cells (pAECs) featuring less common CFTR mutations. This study assessed an alternative approach, using a small scale halide assay that can be adapted for a personalized high throughput setting to analyze CFTR function of pAEC. Methods Pediatric pAECs derived from children with CF (pAEC CF ) were established and expanded as monolayer cultures, before seeding into 96-well plates for the halide assay. Cells were then transduced with an adenoviral construct containing yellow fluorescent protein (eYFP) reporter gene, alone or in combination with either wild-type CFTR (WT-CFTR) or p.Phe508-del CFTR. Four days post transduction, cells were stimulated with forskolin and genistein, and assessed for quenching of the eYFP signal following injection of iodide solution into the assay media. Results Data showed that pAEC CF can express eYFP at high efficiency following transduction with the eYFP construct. The halide assay was able to discriminate functional restoration of CFTR in pAEC CF treated with either WT-CFTR construct or the positive controls syntaxin 8 and B-cell receptor-associated protein 31 shRNAs. Significance The current study demonstrates that the halide assay can be adapted for pediatric pAEC CF to evaluate restoration of CFTR function. With the ongoing development of small molecules to modulate the folding and/or activity of various mutated CFTR proteins, this halide assay presents a small-scale personalized screening platform that could assess therapeutic potential of molecules across a broad range of CFTR mutations