Exercise-induced bronchoconstriction update: therapeutic management

Management of exercise-induced bronchoconstriction (EIB) should include both prevention and treatment directed toward the underlying asthma and bronchial hyperresponsiveness. Both nonpharmacologic and pharmacologic approaches should be followed. Preexercise warm-up, to take advantage of the refractory period that follows EIB, is an important preventive technique. Dietary interventions such as fish oil, vitamin D, and ascorbic acid have shown promising results. Beta 2-agonists are considered the most effective agents for EIB at this time but intermittent use is recommended to avoid tolerance or decreased effectiveness with daily regular use. Leukotriene inhibitors and mast cell stabilizing agents can be useful in EIB but are less effective than beta 2-agonists. Tolerance to beta 2-agonists is not prevented by concomitant use of inhaled corticosteroid but it is not known whether use of leukotriene inhibitors can affect tolerance. EIB in elite athletes with no underlying asthma may have a different pathogenesis.     

Can reality orientation be rehabilitated? Development and piloting of an evidence-based programme of cognition-based therapies for people with dementia

This study describes the development and implementation of a programme of cognition-based therapies for dementia. The programme was designed by distilling the evidence of the effectiveness of Reality Orientation and related approaches, following a broad-based systematic review. The most beneficial elements identified from previous studies were extracted and incorporated into the programme, using the expertise of specialists in the field. The programme comprised of 15 45-min, twice weekly sessions. It ran in one day centre and three residential homes, involving 27 people with dementia (17 treatment and 10 control subjects). The results of the pilot study showed positive trends in cognition, and trends towards reduced depression and anxiety following treatment. No negative effects were identified. We discuss how the outcomes of the pilot study were used to modify the programme, which now has a stronger cognitive element. This refined programme is currently being tested as part of a large multicentre, randomised controlled trial.     

Lack of association between leukocyte telomere length and genetic variants in two ageing-related candidate genes

BACKGROUND: Leukocyte telomere length, a putative marker of ageing, is a highly variable and heritable complex trait. In order to determine the possible underlying genetic variants for leukocyte telomere length variation, we conducted an association study of leukocyte telomere length and two candidate genes for ageing-related traits, TGFB1 and KLOTHO, in a female Caucasian dizygotic twin population. METHODS AND MATERIALS: Terminal restriction fragment (TRF) length, an index of telomere length, was measured using Southern Blotting. Six and four single nucleotide polymorphisms (SNP) were genotyped in TGFB1 and KLOTHO gene, respectively, and tested for association. When there is strong LD between SNPs (r(2) > 0.5), haplotypic association was investigated using haplotype trend regression approach. RESULTS: All SNPs were in Hardy-Weinberg equilibrium (p > 0.05). No significant association was detected for individual SNPs (p > 0.101), or two-locus haplotypes (p = 0.7497) with TRF variation. CONCLUSION: We failed to find any significant association between leukocyte telomere length and 10 SNPs in two ageing-related candidate genes, TGFB1 and KLOTHO. This result suggests that while we could not exclude minor effects, none of 10 SNPs in these two candidate genes showed significant association with the variation of leukocyte telomere length in our cohort. But as it is unclear whether telomere length dynamics is the cause or the effect of the ageing process, it is still possible the genes are associated with ageing via alternate mechanisms.     

Amiloride-insensitive units of the chorda tympani nerve are necessary for normal ammonium chloride detectability in the rat

In spite of its common use as a standard stimulus in peripheral nerve recordings, relatively little is known about the psychophysics of NH-sub-4Cl taste. Rats' detection threshold for this salt was tested under a variety of conditions, including amiloride (100 muM) treatment and bilateral chorda tympani (CT) nerve transection. Detectability was measured with a 2-lever operant discrimination procedure used previously to measure detection thresholds for NaCl and KCl. Although NH-sub-4Cl and KCl appear to share a common taste quality and transduction mechanism, the logistic function and threshold for NH-sub-4Cl were found to be more similar to those of NaCl than to those of KCl. Like that of KCl, however, the detection threshold for NH4Cl increased significantly with CT transection (0.54 log-sub-1-sub-0 units, p < .004), but not with amiloride adulteration. This finding supports the hypothesis that the CT is necessary for normal salt detection regardless of stimulus, and suggests that amiloride does not appreciably impact responses to nonsodium salts at the behavioral level.     

The role of microRNA profiling in prognosticating progression in Ta and T1 urinary bladder cancer

ObjectiveTo analyze microRNA profile in Ta and T1 urinary bladder cancers in combination and separately and to relate this to the risk of later developing higher-stage disease.Materials and methodsFormalin-fixed, paraffin-embedded samples of 44 Ta and 42 T1 bladder cancers representing cases with and without stage progression during follow-up were collected and microRNA expression levels were measured by microarray analysis.ResultsIn a comparison between the progressors and controls, in the Ta/T1 group, miR-10a-5p and miR-31-5p were differentially expressed. miR-10a-5p was also correlated to time to progression (P = 0.00012). In the subgroup analysis, 3 microRNAs, miR-10a-5p, miR-31-5p, and miR-130a-3p, were differentially expressed among Ta tumors and had a fold change of more than 1.5 (P<0.038). The comparison concerning microRNA expression between the progressors and controls in category T1 cancers revealed no significant differences.ConclusionsProfiling revealed that certain microRNAs predicted the risk of developing higher-stage disease among patients with Ta cancers. Lower miR-10a-5p expression in Ta progressing tumors indicates that this microRNA could be important for later malignant potential among this group of patients.