Use of continuous positive airway pressure reduces airway reactivity in adults with asthma

Asthma is characterised by airway hyperreactivity, which is primarily treated with β-adrenergic bronchodilators and anti-inflammatory agents. However, mechanical strain during breathing is an important modulator of airway responsiveness and we have previously demonstrated in animal models that continuous positive airway pressure (CPAP) resulted in lower in vivo airway reactivity. We now evaluated whether using nocturnal CPAP decreased airway reactivity in clinically-stable adults with asthma. Adults with stable asthma and normal spirometry used nocturnal CPAP (8-10 cmH(2)O) or sham treatment (0-2 cmH(2)O) for 7 days. Spirometry and bronchial challenges were obtained before and after treatment. The primary outcome was the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 s (PC(20)). The CPAP group (n=16) had a significant decrease in airway reactivity (change in (Δ)logPC(20) 0.406, p<0.0017) while the sham group (n=9) had no significant change in airway reactivity (ΔlogPC(20) 0.003, p=0.9850). There was a significant difference in the change in airway reactivity for the CPAP versus the sham group (ΔlogPC(20) 0.41, p<0.043). Our findings indicate that chronic mechanical strain of the lungs produced using nocturnal CPAP for 7 days reduced airway reactivity in clinically stable asthmatics. Future studies of longer duration are required to determine whether CPAP can also decrease asthma symptoms and/or medication usage

Deciphering the mechanisms of phonological therapy in jargon aphasia

Background: Severe word production difficulties remain one of the most challenging clinical symptoms to treat in individuals with jargon aphasia. Clinically, it is important to determine why some individuals with jargon aphasia improve following therapy when others do not. We report a therapy study with AM, an individual with severe neologistic jargon aphasia, and provide a subsequent comparison to previous cases, with the purpose of informing both our theoretical and clinical understanding of jargon aphasia. Aims: This research aimed to investigate AM’s locus of word production deficit and determine the effectiveness of Phonological Component Analysis (PCA) therapy, a phonological cueing therapy, in the re-learning and generalization of naming responses for words. In addition, AM’s performance in therapy, linguistic profile, and ability to engage with therapy/cues were compared in a retrospective analysis with the background linguistic and therapy data of two other individuals with jargon aphasia (P9, Leonard et al., 2008; FF, Bose, 2013), who responded differentially to PCA. This was undertake to explore possible prognostic indicators of phonological therapy for jargon aphasia. Methods and Procedures: A battery of linguistic and neuropsychological tests was used to identify AM’s word production deficit. A single-subject multiple probe design across behaviours was employed to evaluate the effects of PCA therapy on the re-learning and generalization of naming responses. In the retrospective analysis of AM, P9 and FF, we compared differences and similarities in performance on various linguistic tasks, the ability to engage in therapy (i.e., ability to generate and utilize the cues), as well as to retain and maintain cues. Outcomes and Results: AM’s locus of deficit was identified in the mapping between semantics and phonology. PCA was found to be effective in improving naming in two of the three treated word lists during the treatment phase; however, these gains were not maintained. Generalization to untreated picture names was not observed. Findings from the retrospective analysis illustrated that oral reading skills, ability to segment phonological information from words and active engagement with provided cues are likely prerequisites for obtaining robust and long-term gains. Conclusions and Implications: We demonstrated that phonological therapy could be beneficial for the remediation of naming abilities at least in the re-learning phase; however, maintenance and generalization of these gains were limited. This research helps to elucidate the considerations and evaluations necessary for the appropriateness of phonological therapy and candidacy of individuals with jargon aphasia for this treatment approach

In search of phylogenetic congruence between molecular and morphological data in bryozoans with extreme adult skeletal heteromorphy

peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=tsab20© Crown Copyright 2015. This document is the author's final accepted/submitted version of the journal article. You are advised to consult the publisher's version if you wish to cite from it

In vivo Identification and Specificity assessment of mRNA markers of hypoxia in human and mouse tumors

<p>Abstract</p> <p>Background</p> <p>Tumor hypoxia is linked to poor prognosis, but identification and quantification of tissue hypoxia remains a challenge. The hypoxia-specificity of HIF-1α target genes in vivo has been questioned due to the confounding influence of other microenvironmental abnormalities known to affect gene expression (e.g., low pH). Here we describe a new technique that by exploiting intratumoral oxygenation heterogeneity allows us to identify and objectively rank the most robust mRNA hypoxia biomarkers.</p> <p>Methods</p> <p>Mice carrying human (FaDu_dd) or murine (SCCVII) tumors were injected with the PET hypoxia tracer FAZA. Four hours post-injection tumors were removed, frozen, and crushed into milligram-sized fragments, which were transferred individually to pre-weighed tubes containing RNAlater and then weighed. For each fragment radioactivity per tissue mass and expression patterns of selected mRNA biomarkers were analyzed and compared.</p> <p>Results</p> <p>In both tumour models, fragmentation into pieces weighing 10 to 60 mg resulted in tissue fragments with highly variable relative content of hypoxic cells as evidenced by an up to 13-fold variation in FAZA radioactivity per mass of tissue. Linear regression analysis comparing FAZA retention with patterns of gene expression in individual tissue fragments revealed that CA9, GLUT1 and LOX mRNA levels were equally and strongly correlated to hypoxic extent in FaDu_dd. The same link between hypoxia and gene expression profile was observed for CA9 and GLUT1, but not LOX, in SCCVII tumors. Apparent in vivo hypoxia-specificity for other putative molecular markers of tissue hypoxia was considerably weaker.</p> <p>Conclusions</p> <p>The portrayed technique allows multiple pairwise measurements of mRNA transcript levels and extent of hypoxia in individual tumors at a smallest possible volumetric scale which (by limiting averaging effects inherent to whole-tumor analysis) strengthen the conclusiveness on true hypoxia-specificity of candidate genes while limiting the required number of tumors. Among tested genes, our study identified CA9, GLUT1 and possibly LOX as highly specific biomarkers of tumor hypoxia in vivo.</p

Aspergillus hancockii sp. Nov., a biosynthetically talented fungus endemic to southeastern Australian soils

Aspergillus hancockii sp. nov., classified in Aspergillus subgenus Circumdati section Flavi, was originally isolated from soil in peanut fields near Kumbia, in the South Burnett region of southeast Queensland, Australia, and has since been found occasionally from other substrates and locations in southeast Australia. It is phylogenetically and phenotypically related most closely to A. leporis States and M. Chr., but differs in conidial colour, other minor features and particularly in metabolite profile. When cultivated on rice as an optimal substrate, A. hancockii produced an extensive array of 69 secondary metabolites. Eleven of the 15 most abundant secondary metabolites, constituting 90% of the total area under the curve of the HPLC trace of the crude extract, were novel. The genome of A. hancockii, approximately 40 Mbp, was sequenced and mined for genes encoding carbohydrate degrading enzymes identified the presence of more than 370 genes in 114 gene clusters, demonstrating that A. hancockii has the capacity to degrade cellulose, hemicellulose, lignin, pectin, starch, chitin, cutin and fructan as nutrient sources. Like most Aspergillus species, A. hancockii exhibited a diverse secondary metabolite gene profile, encoding 26 polyketide synthase, 16 nonribosomal peptide synthase and 15 nonribosomal peptide synthase-like enzymes