Quantifying neighbourhood socioeconomic effects in clustering of behaviour-related risk factors: a multilevel analysis

Background

The extent to which neighbourhood characteristics explain accumulation of health behaviours is poorly understood. We examined whether neighbourhood disadvantage was associated with co-occurrence of behaviour-related risk factors, and how much of the neighbourhood differences in the co-occurrence can be explained by individual and neighbourhood level covariates.

Methods

The study population consisted of 60 694 Finnish Public Sector Study participants in 2004 and 2008. Neighbourhood disadvantage was determined using small-area level information on household income, education attainment, and unemployment rate, and linked with individual data using Global Positioning System-coordinates. Associations between neighbourhood disadvantage and co-occurrence of three behaviour-related risk factors (smoking, heavy alcohol use, and physical inactivity), and the extent to which individual and neighbourhood level covariates explain neighbourhood differences in co-occurrence of risk factors were determined with multilevel cumulative logistic regression.

Results

After adjusting for age, sex, marital status, and population density we found a dose-response relationship between neighbourhood disadvantage and co-occurrence of risk factors within each level of individual socioeconomic status. The cumulative odds ratios for the sum of health risks comparing the most to the least disadvantaged neighbourhoods ranged between 1.13 (95% confidence interval (CI): 1.03–1.24) and 1.75 (95% CI, 1.54–1.98). Individual socioeconomic characteristics explained 35%, and neighbourhood disadvantage and population density 17% of the neighbourhood differences in the co-occurrence of risk factors.

Conclusions

Co-occurrence of poor health behaviours associated with neighbourhood disadvantage over and above individual''s own socioeconomic status. Neighbourhood differences cannot be captured using individual socioeconomic factors alone, but neighbourhood level characteristics should also be considered.     

Identification of a novel idiopathic epilepsy locus in Belgian Shepherd dogs

Epilepsy is the most common neurological disorder in dogs, with an incidence ranging from 0.5% to up to 20% in particular breeds. Canine epilepsy can be etiologically defined as idiopathic or symptomatic. Epileptic seizures may be classified as focal with or without secondary generalization, or as primary generalized. Nine genes have been identified for symptomatic (storage diseases) and one for idiopathic epilepsy in different breeds. However, the genetic background of common canine epilepsies remains unknown. We have studied the clinical and genetic background of epilepsy in Belgian Shepherds. We collected 159 cases and 148 controls and confirmed the presence of epilepsy through epilepsy questionnaires and clinical examinations. The MRI was normal while interictal EEG revealed abnormalities and variable foci in the clinically examined affected dogs. A genome-wide association study using Affymetrix 50K SNP arrays in 40 cases and 44 controls mapped the epilepsy locus on CFA37, which was replicated in an independent cohort (81 cases and 88 controls; combined p = 9.70×10⁻¹⁰, OR = 3.3). Fine mapping study defined a ∼1 Mb region including 12 genes of which none are known epilepsy genes or encode ion channels. Exonic sequencing was performed for two candidate genes, KLF7 and ADAM23. No variation was found in KLF7 but a highly-associated non-synonymous variant, G1203A (R387H) was present in the ADAM23 gene (p = 3.7×10⁻⁸, OR = 3.9 for homozygosity). Homozygosity for a two-SNP haplotype within the ADAM23 gene conferred the highest risk for epilepsy (p = 6.28×10⁻¹¹, OR = 7.4). ADAM23 interacts with known epilepsy proteins LGI1 and LGI2. However, our data suggests that the ADAM23 variant is a polymorphism and we have initiated a targeted re-sequencing study across the locus to identify the causative mutation. It would establish the affected breed as a novel therapeutic model, help to develop a DNA test for breeding purposes and introduce a novel candidate gene for human idiopathic epilepsies.     

Adipose tissue inflammation and liver fat in patients with highly active antiretroviral therapy-associated lipodystrophy

In this cross-sectional study, we sought to determine whether gene expression of macrophage markers and inflammatory chemokines in lipoatrophic subcutaneous abdominal adipose tissue and liver fat content are increased and interrelated in human immunodeficiency virus (HIV)-1-positive, highly active antiretroviral therapy (HAART)-treated patients with lipodystrophy (HAART+LD+; n = 27) compared with those without (HAART+LD-; n = 13). The study groups were comparable with respect to age, gender, and body mass index. The HAART+LD+ group had twofold more intra-abdominal (P = 0.01) and 1.5-fold less subcutaneous (P = 0.091) fat than the HAART+LD- group. As we have reported previously, liver fat was 10-fold higher in the HAART+LD+ compared with the HAART+LD- group (P = 0.00003). Inflammatory gene expression was increased in HAART-lipodystrophy: CD68 4.5-fold (P = 0.000013), tumor necrosis factor (TNF)-alpha 2-fold (P = 0.0094), chemokine (C-C motif) ligand (CCL) 2 2.5-fold (P = 0.0024), CCL3 7-fold (P = 0.0000017), integrin alphaM (ITGAM) 3-fold (P = 0.00067), epidermal growth factor-like module containing, mucin-like, hormone receptor-like (EMR)1 2.5-fold (P = 0.0038), and a disintegrin and metalloproteinase domain (ADAM)8 3.5-fold (P = 0.00057) higher in the HAART+LD+ compared with the HAART+LD- group. mRNA concentration of CD68 (r = 0.37, P = 0.019), ITGAM (r = 0.35, P = 0.025), CCL2 (r = 0.39, P = 0.012), and CCL3 (r = 0.54, P = 0.0003) correlated with liver fat content. In conclusion, gene expression of markers of macrophage infiltration and adipose tissue inflammation is increased in lipoatrophic subcutaneous abdominal adipose tissue of patients with HAART-associated lipodystrophy compared with those without. CD68, ITGAM, CCL2, and CCL3 expression is significantly associated with accumulation of liver fat.     

Sublingual administration of Delta9-tetrahydrocannabinol/beta-cyclodextrin complex increases the bioavailability of Delta9-tetrahydrocannabinol in rabbits

The bioavailability of Delta(9)-tetrahydrocannabinol (THC) was determined after its sublingual administration as solid THC/beta-cyclodextrin (THC/beta-CD) complex, and was compared to oral administration of ethanolic THC, in rabbits. The absolute bioavailability of THC after sublingual administration of solid THC/beta-CD complex powder (16.0 +/- 7.5%; mean +/- SD; n = 4) is higher than the bioavailability of THC after oral administration of ethanolic THC solution (1.3 +/- 1.4%; mean +/- SD; n = 4). The results suggest that sublingual administration of THC/beta-CD complex is a useful tool in improving absolute bioavailability of THC.     

Do house mice use UV cues when foraging?

Research on the behavioural ecology of ultraviolet (UV-A, wavelengths of 320–400 nm, hereafter: UV) sensitivity in terrestrial vertebrates has mainly focused on sexual signalling and foraging in birds and reptiles, whereas the fact that some rodents are also sensitive to UV light has been somewhat ignored. Here, we present the results of two behavioural experiments, which tested whether rodents use UV cues in foraging. In the first experiment we asked whether the colour contrast in the UV waveband is used as a foraging cue. House mice were offered UV-reflecting and UV-absorbing artificial food items in two different illuminations where UV light was either present or absent. The food items were offered to two groups of mice, one group on a UV-reflecting and the other on a UV-absorbing background. The second experiment investigated more specifically whether UV cues are especially important in dawn and dusk when short wavelengths are high in the proportion of available light. House mice showed no preference between the food items regardless of illumination or background. Therefore, our results indicate that house mice do not use UV cues in foraging.     

The Effect of the −308A Allele of the TNF‐α Gene on Insulin Action Is Dependent on Obesity

Objective: Promoter polymorphisms of the tumor necrosis factor alpha (TNF‐α) gene are associated with insulin sensitivity and BMI. We investigated whether the effect of the G‐308A polymorphism of the TNF‐α gene on insulin action depends on BMI. Research Methods and Procedures: The effects of the G‐308A polymorphism on the rates of glucose and lipid oxidation and free fatty acid (FFA) levels were studied using the hyperinsulinemic euglycemic clamp combined with indirect calorimetry in 129 healthy subjects. Results: The ?308A allele of the TNF‐α gene was associated with high rates of glucose oxidation (p = 0.008 adjusted for age, gender, and BMI) and lipid synthesis (p = 0.037) and suppression of FFA levels (p = 0.023) during hyperinsulinemia. In normal weight subjects (BMI < 26 kg/m²), the ?308 allele was associated with high rates of glucose oxidation (p = 0.036) during the clamp but not with high rates of lipid synthesis (p = 0.896) or FFA suppression (p = 0.464). In overweight subjects (BMI ≥ 26 kg/m²), high rates of lipid synthesis and FFA suppression (p = 0.010 and p = 0.042, respectively) but not the rates of glucose oxidation during the clamp (p = 0.193) were associated with the ?308A allele. Discussion: The ?308A allele of the promoter of the TNF‐α gene is associated with high rates of glucose oxidation in normal weight subjects and with effective lipid storage in overweight subjects. These findings suggest an interaction of the polymorphism with obesity.     

Evaluation of the roles of two compatible solutes,glycine betaine and trehalose,for the Acacia senegal–Sinorhizobium symbiosis exposed to drought stress

Plant and Soil - Acacia senegal (Mimosoideae) is a leguminous, nitrogen-fixing tree that grows in arid areas of Africa and the Near East. In this work, we studied the effects of drought stress on...     

Optimization of elastin‐like polypeptide fusions for expression and purification of recombinant proteins in plants

The demand for recombinant proteins for medical and industrial use is expanding rapidly and plants are now recognized as an efficient, inexpensive means of production. Although the accumulation of recombinant proteins in transgenic plants can be low, we have previously demonstrated that fusions with an elastin‐like polypeptide (ELP) tag can significantly enhance the production yield of a range of different recombinant proteins in plant leaves. ELPs are biopolymers with a repeating pentapeptide sequence (VGVPG)_n that are valuable for bioseparation, acting as thermally responsive tags for the non‐chromatographic purification of recombinant proteins. To determine the optimal ELP size for the accumulation of recombinant proteins and their subsequent purification, various ELP tags were fused to green fluorescent protein, interleukin‐10, erythropoietin and a single chain antibody fragment and then transiently expressed in tobacco leaves. Our results indicated that ELP tags with 30 pentapeptide repeats provided the best compromise between the positive effects of small ELP tags (n = 5–40) on recombinant protein accumulation and the beneficial effects of larger ELP tags (n = 80–160) on recombinant protein recovery during inverse transition cycling (ITC) purification. In addition, the C‐terminal orientation of ELP fusion tags produced higher levels of target proteins, relative to N‐terminal ELP fusions. Importantly, the ELP tags had no adverse effect on the receptor binding affinity of erythropoietin, demonstrating the inert nature of these tags. The use of ELP fusion tags provides an approach for enhancing the production of recombinant proteins in plants, while simultaneously assisting in their purification. Biotechnol. Bioeng. 2009;103: 562–573. © 2009 Wiley Periodicals, Inc.