Development and exploratory cluster-randomised opportunistic trial of a theory-based intervention to enhance physical activity among adolescents

Peer reviewedPostprin

Remodelling of human atrial K+ currents but not ion channel expression by chronic β-blockade

Chronic β-adrenoceptor antagonist (β-blocker) treatment in patients is associated with a potentially anti-arrhythmic prolongation of the atrial action potential duration (APD), which may involve remodelling of repolarising K+ currents. The aim of this study was to investigate the effects of chronic β-blockade on transient outward, sustained and inward rectifier K+ currents (ITO, IKSUS and IK1) in human atrial myocytes and on the expression of underlying ion channel subunits. Ion currents were recorded from human right atrial isolated myocytes using the whole-cell-patch clamp technique. Tissue mRNA and protein levels were measured using real time RT-PCR and Western blotting. Chronic β-blockade was associated with a 41% reduction in ITO density: 9.3 ± 0.8 (30 myocytes, 15 patients) vs 15.7 ± 1.1 pA/pF (32, 14), p < 0.05; without affecting its voltage-, time- or rate dependence. IK1 was reduced by 34% at −120 mV (p < 0.05). Neither IKSUS, nor its increase by acute β-stimulation with isoprenaline, was affected by chronic β-blockade. Mathematical modelling suggested that the combination of ITO- and IK1-decrease could result in a 28% increase in APD90. Chronic β-blockade did not alter mRNA or protein expression of the ITO pore-forming subunit, Kv4.3, or mRNA expression of the accessory subunits KChIP2, KChAP, Kvβ1, Kvβ2 or frequenin. There was no reduction in mRNA expression of Kir2.1 or TWIK to account for the reduction in IK1. A reduction in atrial ITO and IK1 associated with chronic β-blocker treatment in patients may contribute to the associated action potential prolongation, and this cannot be explained by a reduction in expression of associated ion channel subunits

Q&A: What is human language, when did it evolve and why should we care?

Human language is unique among all forms of animal communication. It is unlikely that any other species, including our close genetic cousins the Neanderthals, ever had language, and so-called sign 'language' in Great Apes is nothing like human language. Language evolution shares many features with biological evolution, and this has made it useful for tracing recent human history and for studying how culture evolves among groups of people with related languages. A case can be made that language has played a more important role in our species' recent (circa last 200,000 years) evolution than have our genes

Sunitinib mediates mitochondrial ROS production in adult rat cardiac fibroblasts via CaMKII oxidation

Ca2+/calmodulin dependent protein kinase II (CaMKII) is a central mediator of Ca2+-induced signalling in the heart and regulates both normal cardiac physiology and pathology. Sunitinib malate is an oral Type I tyrosine kinase inhibitor (TKI) known to inhibit more than 50 kinases, with anti-angiogenic and anti-proliferative effects affiliated with off-target cardiotoxicity. Previous work has shown that chronic sunitinib treatment significantly increases CaMKII expression and activity and this correlates with significant cardiac dysfunction in vivo.1 Mitochondrial dysfunction, mediated by increased mitochondrial Ca2+ and resultant mitochondrial ROS production, has been proposed as an underlying mechanism for TKI-induced cardiotoxicity in cardiomyocytes.2 However, little is known of how TKIs may affect the non-contractile cells of the heart. Here, we have investigated whether sunitinib treatment increases mitochondrial ROS production in cardiac fibroblasts (CF) and whether CaMKII may play a role in this potential cardiotoxic mechanis

Circumstellar discs: What will be next?

This prospective chapter gives our view on the evolution of the study of circumstellar discs within the next 20 years from both observational and theoretical sides. We first present the expected improvements in our knowledge of protoplanetary discs as for their masses, sizes, chemistry, the presence of planets as well as the evolutionary processes shaping these discs. We then explore the older debris disc stage and explain what will be learnt concerning their birth, the intrinsic links between these discs and planets, the hot dust and the gas detected around main sequence stars as well as discs around white dwarfs.Comment: invited review; comments welcome (32 pages

Validation of a digital photographic method for assessment of dietary quality of school lunch sandwiches brought from home.

Background: It is a challenge to assess children's dietary intake. The digital photographic method (DPM) may be an objective method that can overcome some of these challenges. Objective: The aim of this study was to evaluate the validity and reliability of a DPM to assess the quality of dietary intake from school lunch sandwiches brought from home among children aged 7–13 years. Design: School lunch sandwiches (n=191) were prepared to represent randomly selected school lunch sandwiches from a large database. All components were weighed to provide an objective measure of the composition. The lunches were photographed using a standardised DPM. From the digital images, the dietary components were estimated by a trained image analyst using weights or household measures and the dietary quality was assessed using a validated Meal Index of Dietary Quality (Meal IQ). The dietary components and the Meal IQ obtained from the digital images were validated against the objective weighed foods of the school lunch sandwiches. To determine interrater reliability, the digital images were evaluated by a second image analyst. Results: Correlation coefficients between the DPM and the weighed foods ranged from 0.89 to 0.97. The proportion of meals classified in the same or an adjacent quartile ranged from 98% (starch) to 100% (fruits, vegetables, fish, whole grain, and Meal IQ). There was no statistical difference between fish, fat, starch, whole grains, and Meal IQ using the two methods. Differences were found for fruits and vegetables; Bland–Altman analyses showed a tendency to underestimate high amounts of these variables using the DPM. For interrater reliability, kappa statistics ranged from 0.59 to 0.82 across the dietary components and Meal IQ. Conclusions: The standardised DPM is a valid and reliable method for assessing the dietary quality of school lunch sandwiches brought from home

Development of the chronic obstructive pulmonary disease morning symptom diary (COPD-MSD).

BACKGROUND: The morning tends to be the most difficult time of day for many patients with chronic obstructive pulmonary disease (COPD) when symptoms can limit one's ability to perform even simple activities. Morning symptoms have been linked to higher levels of work absenteeism, thereby increasing the already substantial economic burden associated with COPD. A validated patient-reported outcome (PRO) instrument designed to capture morning symptoms will allow for a more comprehensive approach to the evaluation of treatment benefit in COPD clinical trials. METHODS: A qualitative interview study was conducted among a sample of symptomatic adults with COPD. Concept elicitation interviews (n = 35) were conducted to identify COPD morning symptoms, followed by cognitive interviews (n = 21) to ensure patient comprehension of the items, instructions and response options of the draft COPD Morning Symptom Diary (COPD-MSD). All interview transcript data were coded using ATLAS.ti software for content analysis. RESULTS: Mean age of the concept elicitation and cognitive interview sample was 65.0 years (±7.5) and 62.3 years (±8.3), respectively. The study sample represented the full range of COPD severity (Global Initiative for Chronic Lung Disease [GOLD] classifications I-IV) and included a mix of racial backgrounds, employment status and educational achievement. During the concept elicitation interviews, the three most frequently reported morning symptoms were shortness of breath (n = 35/35; 100 %), phlegm/mucus (n = 31/35; 88.6 %), and cough (n = 30/35; 85.7 %). A group of clinical and instrument development experts convened to review the concept elicitation data and develop the initial 32-item draft COPD-MSD. Cognitive interviews indicated subjects found the draft COPD-MSD to be comprehensive, clear, and easy to understand. The COPD-MSD underwent minor editorial revisions and streamlining based on cognitive interviews and input from the experts to yield the final 19-item daily diary. CONCLUSIONS: This study supports the content validity of the new COPD-MSD and positions the diary for quantitative psychometric testing

Could recombinant insulin compounds contribute to adenocarcinoma progression by stimulating local angiogenesis?

Negative effects on the progression of adenocarcinomas by hyperinsulinaemia and the insulin analogue glargine (A21Gly,B31Arg,B32Arg human insulin) have recently been suggested. Most actions of this insulin analogue have hitherto been explained by direct stimulation of growth potential of neoplastic cells and by its IGF-1 related properties. However, insulin-stimulated angiogenesis could be an additional factor involved in tumour progression and clinical outcomes associated with cancer. Five types of human adenocarcinoma (breast, colon, pancreas, lung and kidney) were evaluated for the presence of insulin receptors (IRs) on angiogenic structures. In an in vitro angiogenesis assay, various commercially available insulin compounds were evaluated for their potential to increase capillary-like tube formation of human microvascular endothelial cells (hMVEC). Insulin compounds used were: human insulin, insulin lispro (B28Lys,B29Pro human insulin), insulin glargine and insulin detemir (B29Lys[e-tetradecanoyl],desB30 human insulin). Insulin receptors were found to be strongly expressed on the endothelium of microvessels in all evaluated adenocarcinomas, in addition to variable expression on tumour cells. Low or no detectable expression of IRs was seen on microvessels in extratumoral stroma. Incubation with commercially available insulin compounds increased capillary-like tube formation of hMVEC in vitro. Our results suggest that all tested insulin compounds may stimulate tumour growth by enhancing local angiogenesis. Future studies need to confirm the association between insulin therapy in type 2 diabetes and tumour progressio