Asthma in childhood: a complex, heterogeneous disease

Asthma in childhood is a heterogeneous disease with different phenotypes and variable clinical manifestations, which depend on the age, gender, genetic background, and environmental influences of the patients. Several longitudinal studies have been conducted to classify the phenotypes of childhood asthma, on the basis of the symptoms, triggers of wheezing illness, or pathophysiological features of the disease. These studies have provided us with important information about the different wheezing phenotypes in young children and about potential mechanisms and risk factors for the development of chronic asthma. The goal of these studies was to provide a better insight into the causes and natural course of childhood asthma. It is well-known that complicated interactions between genes and environmental factors contribute to the development of asthma. Because childhood is a period of rapid growth in both the lungs and the immune system, developmental factors should be considered in the pathogenesis of childhood asthma. The pulmonary system continues to grow and develop until linear growth is completed. Longitudinal studies have reported significant age-related immune development during postnatal early life. These observations suggest that the phenotypes of childhood asthma vary among children and also in an individual child over time. Improved classification of heterogeneous conditions of the disease will help determine novel strategies for primary and secondary prevention and for the development of individualized treatment for childhood asthma

Linear Growth through 12 Years is Weakly but Consistently Associated with Language and Math Achievement Scores at Age 12 Years in 4 Low- or Middle-Income Countries

Background Whether linear growth through age 12 y is associated with language and math achievement at age 12 y remains unclear. Objective Our objective was to investigate associations of linear growth through age 12 y with reading skill, receptive vocabulary, and mathematics performance at age 12 y in 4 low- or middle-income countries (LMICs). Methods We analyzed data from the Young Lives Younger Cohort study in Ethiopia (n = 1275), India (n = 1350), Peru (n = 1402), and Vietnam (n = 1594). Age 1, 5, 8, and 12 y height-for-age z scores (HAZ) were calculated. Language and math achievement at age 12 y was assessed with the use of country-specific adaptations of the Peabody Picture Vocabulary Test, the Early Grades Reading Assessment, and a mathematics test; all test scores were standardized by age within country. We used path analysis to examine associations of HAZ with achievement scores. Twelve models were examined at each age (3 tests across 4 countries). Results Mean HAZ in each country was <–1.00 at all ages. Overall, linear growth through age 12 y was associated with 0.4–3.4% of the variance in achievement scores. HAZ at 1 y was positively and significantly associated with the test score in 11 of the 12 models. This association was significantly mediated through HAZ at 5, 8, and 12 y in 9 of the models. HAZ at 5, 8, and 12 y was positively and significantly associated with test scores in 8, 8, and 6 models, respectively. These associations were mediated through HAZ at older ages in 6 of the HAZ at 5-y models and in 6 of the HAZ at 8-y models. Conclusion Child relative linear growth between ages 1 and 12 y was weakly but consistently associated with language and math achievement at age 12 y in 4 LMICs

Effects of Smoking and Cessation on Subclinical Arterial Disease: A Substudy of a Randomized Controlled Trial

The mechanisms by which smoking cessation reduces cardiovascular disease risk are unclear. We evaluated longitudinal changes in carotid intima-media thickness among current smokers enrolled in a prospective, randomized smoking cessation clinical trial.Subjects were enrolled in a randomized, double-blind, placebo-controlled trial of 5 smoking cessation pharmacotherapies and underwent carotid ultrasonography with carotid intima-media thickness measurement. Subjects were classified as continuously abstinent (biochemically confirmed abstinence at 6 months, 1 year, and 3 years post-quit attempt), intermittently abstinent (reported smoking at one of the three time points), or smoked continuously (reported smoking at all three time points). The primary endpoint was the absolute change (mm) in carotid intima-media thickness (ΔCIMT(max)) before randomization and 3 years after the target quit date. Pearson correlations were calculated and multivariable regression models (controlling for baseline CIMT(max) and research site) were analyzed. Among 795 subjects (45.2 ± 10.6 years old, 58.5% female), 189 (23.8%) were continuously abstinent, 373 (46.9%) smoked continuously, and 233 (29.3%) were abstinent intermittently. There was a greater increase in carotid intima-media thickness among subjects who were continuously abstinent than among those who smoked continuously (p = 0.020), but not intermittently (p = 0.310). Antihypertensive medication use (p = 0.001) and research site (p<0.001) independently predicted ΔCIMTmax--not smoking status. The greatest increase in carotid intima-media thickness among continuous abstainers was related to increases in body-mass index (p = 0.043).Smoking status did not independently predict ΔCIMT(max); increasing body-mass index and antihypertensive medication use were the most important independent predictors. The rapid reduction in cardiovascular disease events observed with smoking cessation is unlikely to be mediated by changes in subclinical atherosclerosis burden.ClinicalTrials.gov NCT00332644

Neural correlates of enhanced visual short-term memory for angry faces: An fMRI study

Copyright: © 2008 Jackson et al.Background: Fluid and effective social communication requires that both face identity and emotional expression information are encoded and maintained in visual short-term memory (VSTM) to enable a coherent, ongoing picture of the world and its players. This appears to be of particular evolutionary importance when confronted with potentially threatening displays of emotion - previous research has shown better VSTM for angry versus happy or neutral face identities.Methodology/Principal Findings: Using functional magnetic resonance imaging, here we investigated the neural correlates of this angry face benefit in VSTM. Participants were shown between one and four to-be-remembered angry, happy, or neutral faces, and after a short retention delay they stated whether a single probe face had been present or not in the previous display. All faces in any one display expressed the same emotion, and the task required memory for face identity. We find enhanced VSTM for angry face identities and describe the right hemisphere brain network underpinning this effect, which involves the globus pallidus, superior temporal sulcus, and frontal lobe. Increased activity in the globus pallidus was significantly correlated with the angry benefit in VSTM. Areas modulated by emotion were distinct from those modulated by memory load.Conclusions/Significance: Our results provide evidence for a key role of the basal ganglia as an interface between emotion and cognition, supported by a frontal, temporal, and occipital network.The authors were supported by a Wellcome Trust grant (grant number 077185/Z/05/Z) and by BBSRC (UK) grant BBS/B/16178

Iron Status and Analysis of Efficacy and Safety of Ferric Carboxymaltose Treatment in Patients with Inflammatory Bowel Disease

Background and Aims:We analyzed iron deficiency and the therapeutic response following intravenous ferric carboxymaltose in a large single-center inflammatory bowel disease (IBD) cohort. Methods: 250 IBD patients were retrospectively analyzed for iron deficiency and iron deficiency anemia. A subgroup was analyzed regarding efficacy and side effects of iron supplementation with ferric carboxymaltose. Results: In the cohort (n = 250), 54.4% of the patients had serum iron levels 60 mu g/dl, 61.6% had ferritin >100 ng/ml, and 90.7% reached Hb >12/13 g/dl at follow-up (p < 0.0001 for all parameters vs. pretreatment values). The most frequent adverse event was a transient increase of liver enzymes with male gender as risk factor (p = 0.008, OR 8.62, 95% CI 1.74-41.66). Conclusions: Iron deficiency and anemia are frequent in IBD patients. Treatment with ferric carboxymaltose is efficious, safe and well tolerated in iron-deficient IBD patients. Copyright (C) 2011 S. Karger AG, Base

Identifying metabolites by integrating metabolome databases with mass spectrometry cheminformatics.

Novel metabolites distinct from canonical pathways can be identified through the integration of three cheminformatics tools: BinVestigate, which queries the BinBase gas chromatography-mass spectrometry (GC-MS) metabolome database to match unknowns with biological metadata across over 110,000 samples; MS-DIAL 2.0, a software tool for chromatographic deconvolution of high-resolution GC-MS or liquid chromatography-mass spectrometry (LC-MS); and MS-FINDER 2.0, a structure-elucidation program that uses a combination of 14 metabolome databases in addition to an enzyme promiscuity library. We showcase our workflow by annotating N-methyl-uridine monophosphate (UMP), lysomonogalactosyl-monopalmitin, N-methylalanine, and two propofol derivatives

Simple, Fast and Accurate Implementation of the Diffusion Approximation Algorithm for Stochastic Ion Channels with Multiple States

The phenomena that emerge from the interaction of the stochastic opening and closing of ion channels (channel noise) with the non-linear neural dynamics are essential to our understanding of the operation of the nervous system. The effects that channel noise can have on neural dynamics are generally studied using numerical simulations of stochastic models. Algorithms based on discrete Markov Chains (MC) seem to be the most reliable and trustworthy, but even optimized algorithms come with a non-negligible computational cost. Diffusion Approximation (DA) methods use Stochastic Differential Equations (SDE) to approximate the behavior of a number of MCs, considerably speeding up simulation times. However, model comparisons have suggested that DA methods did not lead to the same results as in MC modeling in terms of channel noise statistics and effects on excitability. Recently, it was shown that the difference arose because MCs were modeled with coupled activation subunits, while the DA was modeled using uncoupled activation subunits. Implementations of DA with coupled subunits, in the context of a specific kinetic scheme, yielded similar results to MC. However, it remained unclear how to generalize these implementations to different kinetic schemes, or whether they were faster than MC algorithms. Additionally, a steady state approximation was used for the stochastic terms, which, as we show here, can introduce significant inaccuracies. We derived the SDE explicitly for any given ion channel kinetic scheme. The resulting generic equations were surprisingly simple and interpretable - allowing an easy and efficient DA implementation. The algorithm was tested in a voltage clamp simulation and in two different current clamp simulations, yielding the same results as MC modeling. Also, the simulation efficiency of this DA method demonstrated considerable superiority over MC methods.Comment: 32 text pages, 10 figures, 1 supplementary text + figur

Growth trajectories from conception through middle childhood and cognitive achievement at age 8 years: Evidence from four low- and middle-income countries

Child chronic malnutrition is endemic in low- and middle-income countries and deleterious for child development. Studies investigating the relationship between nutrition at different periods of childhood, as measured by growth in these periods (growth trajectories), and cognitive development have produced mixed evidence. Although an explanation of this has been that different studies use different approaches to model growth trajectories, the differences across approaches are not well understood. Furthermore, little is known about the pathways linking growth trajectories and cognitive achievement. In this paper, we develop and estimate a general path model of the relationship between growth trajectories and cognitive achievement using data on four cohorts from Ethiopia, India, Peru, and Vietnam. The model is used to: (a) compare two of the most common approaches to modelling growth trajectories in the literature, namely the lifecourse plot and the conditional body size model, and (b) investigate the potential channels via which the association between growth in each period and cognitive achievement manifests. We show that the two approaches are expected to produce systematically different results that have distinct interpretations. Results suggest that growth from conception through age 1 year, between age 1 and 5 years, and between 5 and 8 years, are each positively and significantly associated with cognitive achievement at age 8 years and that this may be partly explained by the fact that faster-growing children start school earlier. We also find that a significant share of the association between early growth and later cognitive achievement is mediated through growth in interim periods

Reliability of self-reported health risk factors and chronic conditions questions collected using the telephone in South Australia, Australia

Extent: 10p.Background: Accurate monitoring of health conditions and behaviours, and health service usage in the population, using an effective and economical method is important for planning and evaluation. This study examines the reliability of questions asked in a telephone survey by conducting a test/retest analysis of a range of questions covering demographic variables, health risk factors and self-reported chronic conditions among people aged 16 years and over. Methods: A Computer Assisted Telephone Interviewing (CATI) survey on health issues of South Australians was re-administered to a random sub-sample of 154 respondents between 13-35 days (mean 17) after the original survey. Reliability between questions was assessed using Cohen’s kappa and intraclass correlation coefficients. Results: Demographic questions (age, gender, number of adults and children in the household, country of birth) showed extremely high reliability (0.97 to 1.00). Health service use (ICC = 0.90 95% CI 0.86-0.93) and overall health status (Kappa = 0.60 95% CI 0.46-0.75) displayed moderate agreement. Questions relating to self-reported risk factors such as smoking (Kappa = 0.81 95% CI 0.72-0.89) and alcohol drinking (ICC 0.75 = 95% CI 0.63-0.83) behaviour showed good to excellent agreement, while questions relating to self-reported risk factors such as time spent walking for physical activity (ICC 0.47 = 95% CI 0.27-0.61), fruit (Kappaw = 0.60 95% CI 0.45-0.76) and vegetable consumption (Kappaw = 0.50 95% CI 0.32-0.69) showed only moderate agreement. Self-reported chronic conditions displayed substantial to almost perfect agreement (0.72 to 1.00) with the exception of moderate agreement for heart disease (Kappa = 0.82 95% CI 0.57-0.99). Conclusion: These results show the questions assessed to be reliable in South Australia for estimating health conditions and monitoring health related behaviours using a CATI survey.Eleonora Dal Grande, Simon Fullerton and Anne W Taylo