Case-control study of ADARB1 and ADARB2 gene variants in migraine

Background: Migraine causes crippling attacks of severe head pain along with associated nausea, vomiting, photophobia and/or phonophobia. The aim of this study was to investigate single nucleotide polymorphisms (SNPs) in the adenosine deaminase, RNA-specific, B1 (ADARB1)and adenosine deaminase, RNA specific, B2 (ADARB2) genes in an Australian case-control Caucasian population for association with migraine. Both candidate genes are highly expressed in the central nervous system (CNS) and fit criteria for migraine neuropathology. SNPs in the ADARB2 gene were previously found to be positively associated with migraine in a pedigree-based GWAS using the genetic isolate of Norfolk Island, Australia. The ADARB1 gene was also chosen for investigation due to its important function in editing neurotransmitter receptor transcripts. Methods: Four SNPs in ADARB1 and nine in ADARB2 were selected by inspecting blocks of LD in Haploview for genotyping using either TaqMan or Sequenom assays. These SNPs were genotyped in two-hundred and ninety one patients who satisfied the International Classification of Headache Disorders, ICHD-II 2004 diagnostic criteria for migraine and three-hundred and fourteen controls and PLINK was used for association testing. Results: Chi-square (χ2) analysis found no significant association between any of the SNPs tested in the ADARB1 and ADARB2 genes in this study and the occurrence of migraine. Conclusions: In contrast to findings that SNPs in the ADARB2 gene were positively associated with migraine in the Norfolk Island population, we find no evidence to support the involvement of RNA editing genes in migraine susceptibility in an Australian Caucasian population.

Exercise, Appetite Control, and Body Weight Regulation

Exercise has many health benefits and should be an effective weight loss strategy because it increases energy expenditure. However, the success of exercise in producing and sustaining weight loss is influenced by compensatory changes in energy intake and non-exercise activity, among other factors (see King et al. Obesity 15(6):1373–1383, 2007 for a detailed review). The aim of this chapter is to discuss the evidence describing the relationship between exercise and body weight regulation, with a particular focus on appetite control. Evidence is discussed which demonstrates that weight loss responses to exercise are highly variable between individuals. The mechanisms underlying the relationship between exercise, appetite and energy intake, and hence body weight are also discussed. Some people experience an increase in fasting hunger in response to 12 weeks of supervised exercise. However, this is offset by an increase in meal-related satiety in overweight and obese individuals. It is worth noting that weight loss should not be considered as the only successful outcome of an exercise program. Indeed, exercise, even in the absence of weight loss, is associated with numerous health benefits. Nevertheless, an improved understanding of compensatory responses to exercise is vital so that exercise can be more effectively used in weight management; such an understanding may assist us to devise strategies to sustain greater long-term participation in physical activity.

Vertically-aligned graphene flakes on nanoporous templates: morphology, thickness, and defect level control by pre-treatment

Various morphologies of the vertically-aligned graphene flakes were fabricated on the nanoporous templates treated with metal ions in solutions, as well as coated with a thin gold layer and activated in the low-temperature Ar plasma. The thickness and level of structural defects in the graphene flakes could be effectively controlled by a proper selection of the pre-treatment method. We have also demonstrated that various combinations of the flake thickness and defect levels can be obtained, and the morphology and density of the graphene pattern can be effectively controlled. The result obtained could be of interest for various applications requiring fabrication of large graphene networks with controllable properties.

Living well with diabetes: 24-month outcomes from a randomized trial of telephone-delivered weight loss and physical activity intervention to improve glycemic control

OBJECTIVE: To evaluate the effectiveness of a telephone-delivered behavioral weight loss and physical activity intervention targeting Australian primary care patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Pragmatic randomized controlled trial of telephone counseling (n = 151) versus usual care (n = 151). Reported here are 18-month (end-of-intervention) and 24-month (maintenance) primary outcomes of weight, moderate-to-vigorous-intensity physical activity (MVPA; via accelerometer), and HbA1c level. Secondary outcomes include dietary energy intake and diet quality, waist circumference, lipid levels, and blood pressure. Data were analyzed via adjusted linear mixed models with multiple imputation of missing data. RESULTS: Relative to usual-care participants, telephone counseling participants achieved modest, but significant, improvements in weight loss (relative rate [RR] -1.42% of baseline body weight [95% CI -2.54 to -0.30% of baseline body weight]), MVPA (RR 1.42 [95% CI 1.06-1.90]), diet quality (2.72 [95% CI 0.55-4.89]), and waist circumference (-1.84 cm [95% CI -3.16 to -0.51 cm]), but not in HbA1c level (RR 0.99 [95% CI 0.96-1.02]), or other cardio-metabolic markers. None of the outcomes showed a significant change/deterioration over the maintenance period. However, only the intervention effect for MVPA remained statistically significant at 24 months. CONCLUSIONS: The modest improvements in weight loss and behavior change, but the lack of changes in cardio-metabolic markers, may limit the utility, scalability, and sustainability of such an approach.

Mortality reduction following the air pollution control measures during the 2010 Asian Games

Though increased particulate air pollution has been consistently associated with elevated mortality, evidence regarding whether diminished particulate air pollution would lead to mortality reduction is limited. Citywide air pollution mitigation program during the 2010 Asian Games in Guangzhou, China, provided such an opportunity. Daily mortality from non-accidental, cardiovascular and respiratory diseases was compared for 51 intervention days (November 1–December 21) in 2010 with the same calendar date of baseline years (2006–2009 and 2011). Relative risk (RR) and 95% confidence interval (95% CI) were estimated using a time series Poisson model, adjusting for day of week, public holidays, daily mean temperature and relative humidity. Daily PM10 (particle with aerodynamic diameter less than 10 μm) decreased from 88.64 μg/m3 during the baseline period to 80.61 μg/m3 during the Asian Games period. Other measured air pollutants and weather variables did not differ substantially. Daily mortality from non-accidental, cardiovascular and respiratory diseases decreased from 32, 11 and 6 during the baseline period to 25, 8 and 5 during the Games period, the corresponding RR for the Games period compared with the baseline period was 0.79 (95% CI: 0.73–0.86), 0.77 (95% CI: 0.66–0.89) and 0.68 (95% CI: 0.57–0.80), respectively. No significant decreases were observed in other months of 2010 in Guangzhou and intervention period in two control cities. This finding supports the efforts to reduce air pollution and improve public health through transportation restriction and industrial emission control.

An anticipative reactive control strategy to deal with unforeseen obstacles during a multi-sensor-based navigation task

We address the problem of the rangefinder-based avoidance of unforeseen static obstacles during a visual navigation task. We extend previous strategies which are efficient in most cases but remain still hampered by some drawbacks (e.g., risks of collisions or of local minima in some particular cases, etc.). The key idea is to complete the control strategy by adding a controller providing the robot some anticipative skills to guarantee non collision and by defining more general transition conditions to deal with local minima. Simulation results show the proposed strategy efficiency.

Differences in L1 linguistic attention control between monolinguals and bilinguals

Relational elements of language (e.g. spatial prepositions) act to direct attention to aspects of an incoming message. The listener or reader must be able to use these elements to focus and refocus attention on the mental representation being constructed. Research has shown that this type of attention control is specific to language and can be distinguished from attention control for non-relational (semantic or content) elements. Twenty-two monolinguals (18–30 years) and nineteen bilinguals (18–30 years) completed two conditions of an alternating-runs task-switching paradigm in their first language. The relational condition involved processing spatial prepositions, and the non-relational condition involved processing concrete nouns and adjectives. Overall, monolinguals had significantly larger shift costs (i.e. greater attention control burden) in the relational condition than the non-relational condition, whereas bilinguals performed similarly in both conditions. This suggests that proficiency in a second language has a positive impact on linguistic attention control in one's native language.

Carvedilol induces greater control of β2- than β1-adrenoceptor-mediated inotropic and lusitropic effects by PDE3, while PDE4 has no effect in human failing myocardium

The beta-blockers carvedilol and metoprolol provide important therapeutic strategies for heart failure treatment. Therapy with metoprolol facilitates the control by phosphodiesterase PDE3, but not PDE4, of inotropic effects of catecholamines in human failing ventricle. However, it is not known whether carvedilol has the same effect. We investigated whether the PDE3-selective inhibitor cilostamide (0.3 mu M) or PDE4-selective inhibitor rolipram (1 mu M) modified the positive inotropic and lusitropic effects of catecholamines in ventricular myocardium of heart failure patients treated with carvedilol. Right ventricular trabeculae from explanted hearts of nine carvedilol-treated patients with terminal heart failure were paced to contract at 1 Hz. The effects of (-)-noradrenaline, mediated through beta(1)-adrenoceptors (beta(2)-adrenoceptors blocked with ICI118551), and (-)-adrenaline, mediated through beta(2)-adrenoceptors (beta(1)-adrenoceptors blocked with CGP20712A), were assessed in the absence and presence of the PDE inhibitors. The inotropic potency, estimated from -logEC(50)s, was unchanged for (-)-noradrenaline but decreased 16-fold for (-)-adrenaline in carvedilol-treated compared to non-beta-blocker-treated patients, consistent with the previously reported beta(2)-adrenoceptor-selectivity of carvedilol. Cilostamide caused 2- to 3-fold and 10- to 35-fold potentiations of the inotropic and lusitropic effects of (-)-noradrenaline and (-)-adrenaline, respectively, in trabeculae from carvedilol-treated patients. Rolipram did not affect the inotropic and lusitropic potencies of (-)-noradrenaline or (-)-adrenaline. Treatment of heart failure patients with carvedilol induces PDE3 to selectively control the positive inotropic and lusitropic effects mediated through ventricular beta(2)-adrenoceptors compared to beta(1)-adrenoceptors. The beta(2)-adrenoceptor-selectivity of carvedilol may provide protection against beta(2)-adrenoceptor-mediated ventricular overstimulation in PDE3 inhibitor-treated patients. PDE4 does not control beta(1)- and beta(2)-adrenoceptor-mediated inotropic and lusitropic effects in carvedilol-treated patients.

Profiles of illicit drug use during annual key holiday and control periods in Australia: Wastewater analysis in an urban, a semi-rural and a vacation area

AIMS: To examine changes in illicit drug consumption between peak holiday season (23 December-3 January) in Australia and a control period two months later in a coastal urban area, an inland semi-rural area and an island populated predominantly by vacationers during holidays. DESIGN: Analysis of representative daily composite wastewater samples collected from the inlet of the major wastewater treatment plant in each area. SETTING: Three wastewater treatment plants. PARTICIPANTS: Wastewater treatment plants serviced approximately 350, 000 persons in the urban area, 120,000 in the semi-rural area and 1100-2400 on the island. MEASUREMENTS: Drug residues were analysed using liquid chromatography coupled to a tandem mass spectrometer. Per capita drug consumption was estimated. Changes in drug use were quantified using Hedges' g. FINDINGS: During the holidays, cannabis consumption in the semi-rural area declined (g = -2.8) as did methamphetamine (-0.8), whereas cocaine (+1.5) and ecstasy (+1.6) use increased. In the urban area, consumption of all drugs increased during holidays (cannabis +1.6, cocaine +1.2, ecstasy +0.8 and methamphetamine +0.3). In the vacation area, methamphetamine (+0.7), ecstasy (+0.7) and cocaine (+1.1) use increased, but cannabis (-0.5) use decreased during holiday periods. CONCLUSIONS: While the peak holiday season in Australia is perceived as a period of increased drug use, this is not uniform across all drugs and areas. Substantial declines in drug use in the semi-rural area contrasted with substantial increases in urban and vacation areas. Per capita drug consumption in the vacation area was equivalent to that in the urban area, implying that these locations merit particular attention for drug use monitoring and harm minimisation measures.

Illicit drug use between an annual key holiday and a control period: Wastewater analysis in a semi-rural, an urban and a vacation area

Introduction and Aims: Holiday periods are potentially a time for increased substance use as social events and private parties are more common. Data on community illicit drug consumption during holiday periods are limited. Besides existing methods for determining drug use, such as population surveys, one emerging method is to measure illicit drugs and/or their metabolites in wastewater samples. This study examined the change in consumption of cannabis, methamphetamine, cocaine and 3,4- methylenedioxymethamphetamine in three different types of areas (an inland semi-rural area, a coastal urban area and a vacation island) with respect to holiday times. Design and Methods: Samples were collected at the inlet of the major wastewater treatment plant in each area during a key annual holiday (i.e. the summer holiday including Christmas and New Year) and control period. Illicit drug residues in the daily composited samples were measured by liquid chromatography coupled with tandem mass spectrometry. Results: Drug use varied substantially among the three areas within each monitoring period as well as between the holiday and control period within each area. Use consistently increased and peaked over New Year particularly for cocaine and 3,4-methylenedioxymethamphetamine whereas cannabis and methamphetamine were relatively less subjected to holiday times in all the areas. Discussion and Conclusions: Wastewater sampling and analysis provides higher spatio-temporal resolution than national surveys and supplements drug epidemiology studies originating primary in metropolitan locations. Such data is essential for policy makers to plan potential intervention strategies associated with these illicit substances in regional areas and other settings besides urban areas in the future.

Excess water storage depth - A water management practice to control simetryn and thiobencarb runoff from paddy fields

Experiments were carried out to verify the effectiveness of the excess water storage depth (EWSD) in reducing runoff losses of simetryn and thiobencarb from paddy fields upon appreciable rainfall events. A paddy plot having an EWSD of 2 cm was effective in controlling runoff with the herbicide losses of less than 1% of the applied herbicides. Meanwhile, a plot with 0-cm EWSD lost 18.1 and 3.7% of the applied mass of simetryn and thiobencarb, respectively. Therefore, an appropriate EWSD is essential during the recommended 7-day water holding period in order to completely hold the water inside the field in case of rainfall.

Applicability of ELISA in pesticide monitoring to control runoff of bensulfuron-methyl and simetryn from paddy fields

The applicability of ELISA kits was evaluated as an alternative to monitor bensulfuron-methyl and simetryn behavior in paddy water under intermittent (Plot 1) and continuous (Plot 2) irrigation schemes. Simetryn concentrations in both plots decreased exponentially from the peak of the first day. However, the simetryn kit systematically underestimated by a factor of 0.79 as compared to the GC method. Bensulfuron-methyl concentrations exhibited similar dissipation kinetics in paddy water and the drainage water. The bensulfuron-methyl kit was capable of distinguishing spatial variations of concentrations in the paddy field. The ELISA kits clearly indicated differences in the loss of both herbicides between the two plots and therefore may be useful for evaluating the water management practice of pesticide runoff control in paddy fields.

High-resolution SNP microarray investigation of copy number variations on chromosome 18 in a control cohort

Copy number variations (CNVs) as described in the healthy population are purported to contribute significantly to genetic heterogeneity. Recent studies have described CNVs using lymphoblastoid cell lines or by application of specifically developed algorithms to interrogate previously described data. However, the full extent of CNVs remains unclear. Using high-density SNP array, we have undertaken a comprehensive investigation of chromosome 18 for CNV discovery and characterisation of distribution and association with chromosome architecture. We identified 399 CNVs, of which loss represents 98%, 58% are less than 2.5 kb in size and 71% are intergenic. Intronic deletions account for the majority of copy number changes with gene involvement. Furthermore, one-third of CNVs do not have putative breakpoints within repetitive sequences. We conclude that replicative processes, mediated either by repetitive elements or microhomology, account for the majority of CNVs in the healthy population. Genomic instability involving the formation of a non-B structure is demonstrated in one region.

Association between the interleukin 23 receptor and ankylosing spondylitis is confirmed by a new UK case-control study and meta-analysis of published series

Objectives. It has been shown previously that IL-23R variants are associated with AS. We conducted an extended analysis in the UK population and a meta-analysis with the previously published studies, in order to refine these IL-23R associations with AS. Methods. The UK case-control study included 730 new cases and 1331 healthy controls. In the extended study, the 730 cases were combined with 1088 published cases. Allelic associations were analysed using contingency tables. In the meta-analysis, 3482 cases and 3150 controls from four different published studies and the new UK cases were combined. DerSimonian-Laird test was used to calculate random effects pooled odds ratios (ORs). Results. In the UK case-control study with new cases, four of the eight SNPs showed significant associations, whereas in the extended UK study, seven of the eight IL-23R SNPs showed significant associations (P < 0.05) with AS, maximal with rs11209032 (P < 10-5, OR 1.3), when cases with IBD and/or psoriasis were excluded. The meta-analysis showed significant associations with all eight SNPs; the strongest associations were again seen not only with rs11209032 (P = 4.06 × 10-9, OR ∼1.2) but also with rs11209026 (P < 10-10, OR ∼0.6). Conclusions. IL-23R polymorphisms are clearly associated with AS, but the primary causal association(s) is(are) still not established. These polymorphisms could contribute either increased or decreased susceptibility to AS; functional studies will be required for their full evaluation. Additionally, observed stronger associations with SNPs rs11209026 and rs11465804 upon exclusion of IBD and/or psoriasis cases may represent an independent association with AS. © The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.